Datasets:

mattany

/

wikipedia-biology-rag-sample

like 0

Survival analysis If the event of interest has already happened before the subject is included in the study but it is not known when it occurred, the data is said to be "left-censored". When it can only be said that the event happened between two observations or examinations, this is "interval censoring". Left censoring occurs for example when a permanent tooth has already emerged prior to the start of a dental study that aims to estimate its emergence distribution. In the same study, an emergence time is interval-censored when the permanent tooth is present in the mouth at the current examination but not yet at the previous examination. Interval censoring often occurs in HIV/AIDS studies. Indeed, time to HIV seroconversion can be determined only by a laboratory assessment which is usually initiated after a visit to the physician. Then one can only conclude that HIV seroconversion has happened between two examinations. The same is true for the diagnosis of AIDS, which is based on clinical symptoms and needs to be confirmed by a medical examination. It may also happen that subjects with a lifetime less than some threshold may not be observed at all: this is called "truncation". Note that truncation is different from left censoring, since for a left censored datum, we know the subject exists, but for a truncated datum, we may be completely unaware of the subject. Truncation is also common. In a so-called "delayed entry" study, subjects are not observed at all until they have reached a certain age

Biology

https://en.wikipedia.org/wiki?curid=419259

Survival analysis

Survival analysis For example, people may not be observed until they have reached the age to enter school. Any deceased subjects in the pre-school age group would be unknown. Left-truncated data are common in actuarial work for life insurance and pensions. Left-censored data can occur when a person's survival time becomes incomplete on the left side of the follow-up period for the person. For example, in an epidemiological example, we may monitor a patient for an infectious disorder starting from the time when he or she is tested positive for the infection. Although we may know the right-hand side of the duration of interest, we may never know the exact time of exposure to the infectious agent. Survival models can be usefully viewed as ordinary regression models in which the response variable is time. However, computing the likelihood function (needed for fitting parameters or making other kinds of inferences) is complicated by the censoring. The likelihood function for a survival model, in the presence of censored data, is formulated as follows. By definition the likelihood function is the conditional probability of the data given the parameters of the model. It is customary to assume that the data are independent given the parameters. Then the likelihood function is the product of the likelihood of each datum. It is convenient to partition the data into four categories: uncensored, left censored, right censored, and interval censored. These are denoted "unc.", "l.c.", "r.c.", and "i.c." in the equation below

Biology

https://en.wikipedia.org/wiki?curid=419259

Survival analysis

Survival analysis For uncensored data, with formula_32 equal to the age at death, we have For left-censored data, such that the age at death is known to be less than formula_32, we have For right-censored data, such that the age at death is known to be greater than formula_32, we have For an interval censored datum, such that the age at death is known to be less than formula_38 and greater than formula_39, we have An important application where interval-censored data arises is current status data, where an event formula_41 is known not to have occurred before an observation time and to have occurred before the next observation time. The Kaplan-Meier estimator can be used to estimate the survival function. The Nelson–Aalen estimator can be used to provide a non-parametric estimate of the cumulative hazard rate function. The UCLA website http://www.ats.ucla.edu/stat/ has numerous examples of statistical analyses using SAS, R, SPSS and STATA, including survival analyses. The textbook by Kleinbaum has examples of survival analyses using SAS, R, and other packages. The textbooks by Brostrom, Dalgaard and Tableman and Kim give examples of survival analyses using R (or using S, and which run in R).

Biology

https://en.wikipedia.org/wiki?curid=419259

Survival analysis

Indoor residual spraying or IRS is the process of spraying the inside of dwellings with an insecticide to kill mosquitoes that spread malaria. A dilute solution of insecticide is sprayed on the inside walls of certain types of dwellings—those with walls made from porous materials such as mud or wood but not plaster as in city dwellings. Mosquitoes are killed or repelled by the spray, preventing the transmission of the disease. In 2008, 44 countries employed IRS as a malaria control strategy. Several pesticides have historically been used for IRS, the first and most well-known being DDT. The World Health Organization (WHO) recommends IRS as one of three primary means of malaria control, the others being use of insecticide treated bednets (ITNs) and prompt treatment of confirmed cases with artemisinin-based combination therapies (ACTs). While previously the WHO had recommended IRS only in areas of sporadic malaria transmission, in 2006 it began recommending IRS in areas of endemic, stable transmission as well.<ref name="DDTBP.1/2"></ref> According to the WHO: Furthermore, for IRS to be effective: The WHO further states that "insecticide susceptibility and vector behaviour; safety for humans and the environment; and efficacy and cost-effectiveness" are factors that must be considered when selecting an insecticide for IRS. Currently, the WHO has approved twelve different insecticides for IRS. According to 2010 Cochrane review, IRS is an effective strategy for reducing malaria incidence

Biology

https://en.wikipedia.org/wiki?curid=14667005

Indoor residual spraying

Indoor residual spraying It is about as effective as using insecticide treated nets (ITN)s, though ITNs may be a more effective at reducing morbidity in some situations. Few studies have directly compared the cost effectiveness of IRS directly with other methods of malaria control. A study from 2008 assessed the cost effectiveness of seven African anti-malaria campaigns: two IRS campaigns and five insecticide treated bednet (ITN) distribution campaigns. The authors found that on a cost-per-child-death-averted basis, all were about the same, but the ITN campaigns were slightly more cost effective. With regard to the cost effectiveness of various pesticides vis-a-vis each other for IRS, historically DDT has been considered the most cost effective, mainly because it lasts longer than alternatives and therefore dwellings can be sprayed less frequently. But actual studies on cost effectiveness are lacking, and none have taken into account the adverse health and environmental effects of DDT or its alternatives. The United Nations Environment Programme (UNEP) concluded in 2008 that "IRS with DDT remains affordable and effective in many situations but, with regard to the direct costs, the relative advantage of DDT vis-à-vis alternative insecticides seems to be diminishing. The contextual evidence base on cost-effectiveness needs strengthening, and the external costs of DDT use vis-à-vis alternative insecticides require a careful assessment

Biology

https://en.wikipedia.org/wiki?curid=14667005

Indoor residual spraying

Indoor residual spraying " For IRS to be effective, at least 80% of homes and barns in an area must be sprayed, and if enough residents refuse spraying, the effectiveness of the whole program can be jeopardized. Many residents resist spraying of DDT in particular. This is due to a variety of factors, including its smell and the stains it leaves on the walls. While that stain makes it easier to check whether the room has been sprayed, it causes some villagers to resist the spraying of their homes or to resurface the wall, which eliminates the residual insecticidal effect. Pyrethroid insecticides are reportedly more acceptable since they do not leave visible residues on the walls. In addition, DDT is not suitable for this type of spraying in Western-style plastered or painted walls, only traditional dwellings with unpainted walls made of mud, sticks, dung, thatch, clay, or cement. As rural areas of South Africa become more prosperous, there is a shift towards Western style housing, leaving fewer homes suitable for DDT spraying, and necessitating the use of alternative insecticides. Other villagers object to DDT spraying because it does not kill cockroaches or bedbugs; rather, it excites such pests making them more active, so that often the use of another insecticide is additionally required. Pyrethroids such as deltamethrin and lambdacyhalothrin, on the other hand, are more acceptable to residents because they kill these nuisance insects as well as mosquitoes

Biology

https://en.wikipedia.org/wiki?curid=14667005

Indoor residual spraying

Indoor residual spraying DDT has also been known to kill beneficial insects, such as wasps that kill caterpillars that, unchecked, destroy thatched roofs. As a result, Mozambique's chief of infectious disease control, Avertino Barreto, says that resistance to DDT spraying is "homegrown", not due to "pressure from environmentalists". "They only want us to use DDT on poor, rural black people," he says. "So whoever suggests DDT use, I say, 'Fine, I'll start spraying in your house first.'" As discussed above, DDT is one of 12 insecticides currently approved by the WHO for use in malaria control. The following table shows recent per country use of DDT for IRS. Unless otherwise noted, data for 2003–07 is from the 2008 Stockholm Convention/UNEP monograph on the current status of DDT, 2008 data is from the WHO's World Malaria Report 2009, and 2009 data is from the 2010 report of the Stockholm Convention's DDT expert group.<ref name="COP.5/5"></ref> The World Malaria Report 2009 does not report the amount of DDT used in each country, only whether it is used or not. Accordingly, countries are listed as using 0 or "some" DDT. Use statistics for 2009-2011 are available from a report of Stockholm Convention's DDT Export Group

Biology

https://en.wikipedia.org/wiki?curid=14667005

Indoor residual spraying

HUGO Gene Nomenclature Committee The (HGNC) is a committee of the Human Genome Organisation (HUGO) that sets the standards for human gene nomenclature. The HGNC approves a "unique" and "meaningful" name for every known human gene, based on a query of experts. In addition to the name, which is usually 1 to 10 words long, the HGNC also assigns a symbol (a short group of characters) to every gene. As with an SI symbol, a gene symbol is like an abbreviation but is more than that, being a second unique name that can stand on its own just as much as substitute for the longer name. It may not necessarily "stand for" the initials of the name, although many gene symbols do reflect that origin. Especially gene abbreviations/symbols but also full gene names are often not specific for a single gene. A marked example is CAP which can refer to any of 6 different genes ("BRD4", "CAP1", "HACD1", "LNPEP", "SERPINB6", and "SORBS1"). The HGNC short gene names, or gene symbols, unlike previously used or published symbols, are specifically assigned to one gene only. This can result in less common abbreviations being selected but reduces confusion as to which gene is referred to. The HGNC summarises its approach to naming genes and assigning "symbols" (gene name abbreviations) as follows: The full description of HGNC's nomenclature guidelines can be found on their web site . HGNC advocates the appendices "_v1, _v2.." to distinguish between different splice variants and "_pr1, _pr2.." for promoter variants of a single gene

Biology

https://en.wikipedia.org/wiki?curid=15396145

HUGO Gene Nomenclature Committee

HUGO Gene Nomenclature Committee HGNC also states that "gene nomenclature should "evolve with new technology" rather than be restrictive as sometimes occurs when historical and single gene nomenclature systems are applied." Comprehensive human gene naming guidelines were last published in 2002, but the HGNC has subsequently issued guides to specific locus types such as endogenous retroviral loci, structural variants and non-coding RNAs. When assigning new gene nomenclature the HGNC make efforts to contact authors who have published on the human gene in question by email, and their responses to the proposed nomenclature are requested. HGNC also coordinates with the related Mouse and Rat Genomic Nomenclature Committees, other database curators, and experts for given specific gene families or sets of genes. The gene name revision procedure is similar to the naming procedure, but changing a standardised gene name after establishment of a consensus can create confusion and the merit of this is therefore controversial. For this reason the HGNC aims to change a gene name only if agreement for that change can be reached among a majority of researchers working on that gene. A complete list of all HGNC-approved gene symbols for protein-coding genes:

Biology

https://en.wikipedia.org/wiki?curid=15396145

HUGO Gene Nomenclature Committee

M1G MG (pyrimido[1,2-"a"]purin-10("3H")-one) is a heterocyclic compound which is a by-product of base excision repair (BER) of a specific type of DNA adduct called MdG. The MdG adduct in turn is formed by a condensation reaction between guanosine nucleotides in DNA and either malondialdehyde (propanedial) or acrolein. If not repaired, these adducts are mutagenic and carcinogenic. Malondialdehyde is an end product of lipid peroxidation while acrolein is a result of DNA peroxidation. MdG is the major endogenous DNA adduct in humans. MdG adducts have been detected in cell DNA in liver, leucocytes, pancreas and breast in concentrations of 1-120 per 10 nucleotides. Detection and quantification of MdG adducts in the body as measured by free MG is a tool for detecting DNA damage that may lead to cancer. Free MG is also biomarker for oxidative stress.

Biology

https://en.wikipedia.org/wiki?curid=15417575

M1G

Cellular model Creating a cellular model has been a particularly challenging task of systems biology and mathematical biology. It involves developing efficient algorithms, data structures, visualization and communication tools to orchestrate the integration of large quantities of biological data with the goal of computer modeling. It is also directly associated with bioinformatics, computational biology and Artificial life. It involves the use of computer simulations of the many cellular subsystems such as the networks of metabolites and enzymes which comprise metabolism, signal transduction pathways and gene regulatory networks to both analyze and visualize the complex connections of these cellular processes. The complex network of biochemical reaction/transport processes and their spatial organization make the development of a predictive model of a living cell a grand challenge for the 21st century. The eukaryotic cell cycle is very complex and is one of the most studied topics, since its misregulation leads to cancers. It is possibly a good example of a mathematical model as it deals with simple calculus but gives valid results. Two research groups have produced several models of the cell cycle simulating several organisms

Biology

https://en.wikipedia.org/wiki?curid=24044102

Cellular model

Cellular model They have recently produced a generic eukaryotic cell cycle model which can represent a particular eukaryote depending on the values of the parameters, demonstrating that the idiosyncrasies of the individual cell cycles are due to different protein concentrations and affinities, while the underlying mechanisms are conserved (Csikasz-Nagy et al., 2006). By means of a system of ordinary differential equations these models show the change in time (dynamical system) of the protein inside a single typical cell; this type of model is called a deterministic process (whereas a model describing a statistical distribution of protein concentrations in a population of cells is called a stochastic process). To obtain these equations an iterative series of steps must be done: first the several models and observations are combined to form a consensus diagram and the appropriate kinetic laws are chosen to write the differential equations, such as rate kinetics for stoichiometric reactions, Michaelis-Menten kinetics for enzyme substrate reactions and Goldbeter–Koshland kinetics for ultrasensitive transcription factors, afterwards the parameters of the equations (rate constants, enzyme efficiency coefficients and Michaelis constants) must be fitted to match observations; when they cannot be fitted the kinetic equation is revised and when that is not possible the wiring diagram is modified. The parameters are fitted and validated using observations of both wild type and mutants, such as protein half-life and cell size

Biology

https://en.wikipedia.org/wiki?curid=24044102

Cellular model

Cellular model In order to fit the parameters the differential equations need to be studied. This can be done either by simulation or by analysis. In a simulation, given a starting vector (list of the values of the variables), the progression of the system is calculated by solving the equations at each time-frame in small increments. In analysis, the properties of the equations are used to investigate the behavior of the system depending of the values of the parameters and variables. A system of differential equations can be represented as a vector field, where each vector described the change (in concentration of two or more protein) determining where and how fast the trajectory (simulation) is heading. Vector fields can have several special points: a stable point, called a sink, that attracts in all directions (forcing the concentrations to be at a certain value), an unstable point, either a source or a saddle point which repels (forcing the concentrations to change away from a certain value), and a limit cycle, a closed trajectory towards which several trajectories spiral towards (making the concentrations oscillate). A better representation which can handle the large number of variables and parameters is called a bifurcation diagram (bifurcation theory): the presence of these special steady-state points at certain values of a parameter (e.g

Biology

https://en.wikipedia.org/wiki?curid=24044102

Cellular model

Cellular model mass) is represented by a point and once the parameter passes a certain value, a qualitative change occurs, called a bifurcation, in which the nature of the space changes, with profound consequences for the protein concentrations: the cell cycle has phases (partially corresponding to G1 and G2) in which mass, via a stable point, controls cyclin levels, and phases (S and M phases) in which the concentrations change independently, but once the phase has changed at a bifurcation event (cell cycle checkpoint), the system cannot go back to the previous levels since at the current mass the vector field is profoundly different and the mass cannot be reversed back through the bifurcation event, making a checkpoint irreversible. In particular the S and M checkpoints are regulated by means of special bifurcations called a Hopf bifurcation and an infinite period bifurcation. Cell Collective is a modeling software that enables one to house dynamical biological data, build computational models, stimulate, break and recreate models. The development is led by Tomas Helikar, a researcher within the field of computational biology. It is designed for biologists, students learning about computational biology, teachers focused on teaching life sciences, and researchers within the field of life science

Biology

https://en.wikipedia.org/wiki?curid=24044102

Cellular model

Cellular model The complexities of math and computer science are built into the backend and one can learn about the methods used for modeling biological species, but complex math equations, algorithms, programming are not required and hence won't impede model building. The mathematical framework behind Cell Collective is based on a common qualitative (discrete) modeling technique where the regulatory mechanism of each node is described with a logical function [for more comprehensive information on logical modeling, see ]. Model validation The model was constructed using local (e.g., protein–protein interaction) information from the primary literature. In other words, during the construction phase of the model, there was no attempt to determine the local interactions based on any other larger phenotypes or phenomena. However, after the model was completed, verification of the accuracy of the model involved testing it for the ability to reproduce complex input–output phenomena that have been observed in the laboratory. To do this, the T-cell model was simulated under a multitude of cellular conditions and analyzed in terms of input–output dose–response curves to determine whether the model behaves as expected, including various downstream effects as a result of activation of the TCR, G-protein-coupled receptor, cytokine, and integrin pathways. The E-Cell Project aims "to make precise whole cell simulation at the molecular level possible". CytoSolve - developed by V. A. Shiva Ayyadurai and C. Forbes Dewey Jr

Biology

https://en.wikipedia.org/wiki?curid=24044102

Cellular model

Cellular model of Department of Biological Engineering at the Massachusetts Institute of Technology - provided a method to model the whole cell by dynamically integrating multiple molecular pathway models. ." In the July 2012 issue of "Cell", a team led by Markus Covert at Stanford published the most complete computational model of a cell to date. The model of the roughly 500-gene "Mycoplasma genitalium" contains 28 algorithmically-independent components incorporating work from over 900 sources. It accounts for interactions of the complete genome, transcriptome, proteome, and metabolome of the organism, marking a significant advancement for the field. Most attempts at modeling cell cycle processes have focused on the broad, complicated molecular interactions of many different chemicals, including several cyclin and cyclin-dependent kinase molecules as they correspond to the S, M, G1 and G2 phases of the cell cycle. In a 2014 published article in PLOS computational biology, collaborators at University of Oxford, Virginia Tech and Institut de Génétique et Développement de Rennes produced a simplified model of the cell cycle using only one cyclin/CDK interaction. This model showed the ability to control totally functional cell division through regulation and manipulation only the one interaction, and even allowed researchers to skip phases through varying the concentration of CDK. This model could help understand how the relatively simple interactions of one chemical translate to a cellular level model of cell division

Biology

https://en.wikipedia.org/wiki?curid=24044102

Cellular model

Cellular model Multiple projects are in progress.

Biology

https://en.wikipedia.org/wiki?curid=24044102

Cellular model

Order of Maternal Glory The () was a Soviet civilian award created on 8 July 1944 by Joseph Stalin and established with a decision of the Presidium of Supreme Soviet of the USSR. Its status was confirmed by the Soviet's decision of 18 August 1944 and later modified by 16 September 1947, 28 May 1973 and 28 May 1980 decisions. It was awarded on behalf of the Presidium of Supreme Soviet of the USSR through decrees of local Soviet presidencies. The order was divided into three classes: first, second and third class. It was conferred to: The order was conferred upon the first birthday of the last child, provided that the other children necessary to reach the qualifying number (natural or adopted) remained alive. Children who had perished under heroic, military or other respectful circumstances, including occupational diseases, were also counted. The award was created simultaneously with the Mother Heroine () order and the Maternity Medal () and it was situated in between them. The author of the art project was the painter Goznaka. The first decree for bestowing the award was issued on 6 December 1944, when the first class order was conferred to 21 women, the second class to 26 and the third class to 27. In total the order was awarded in the first class to 753,000 women, 1,508,000 received the second class award and 2,786,000 received the third class award. First class medals were totally silver made in a convex egg-shape. They were high and wide

Biology

https://en.wikipedia.org/wiki?curid=27554526

Order of Maternal Glory

Order of Maternal Glory In the upper part of the medal contained a red enamel flag with the phrase (Maternal Glory) and the Roman number showing the order's class. Below the flag, there was a white enamel shield with the (USSR) inscription. The upper part of the shield was decorated with a five-pointed star and the lower part with the hammer and sickle symbol. On the left side, there was a figure of a mother holding a son in her arms covered with roses on her lowest part. The lower part of the medal contains a flag and gilded lettering. In second class medals, the flag's enamel was dark-blue and there were not gilded parts while in the third class ones enamel disappeared from the flag, shield and star. The back of the medals was in white enamel. First class medals were suspended to a single light-blue fringe while second class had two light-blue fringes and third class three of them.

Biology

https://en.wikipedia.org/wiki?curid=27554526

Order of Maternal Glory

Wyss Institute for Biologically Inspired Engineering The is a cross-disciplinary research institute at Harvard University which focuses on developing new bioinspired materials and devices for applications in healthcare, manufacturing, robotics, energy, and sustainable architecture. The Institute has two sites: one in the Center for Life Science building in Boston’s Longwood Medical Area and one on Harvard's main campus in Cambridge, Massachusetts. The Wyss Institute was launched in January 2009 with a $125 million gift to Harvard—at the time, the largest single philanthropic gift in its history—from Hansjörg Wyss. In 2013, Hansjörg Wyss doubled his gift to $250 million and in 2019 he donated a further $131 million. The Institute works as an alliance between Harvard Medical School, Harvard School of Dental Medicine, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard Faculty of Arts and Sciences, Boston Children’s Hospital, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Boston University, Brigham and Women's Hospital, Massachusetts General Hospital, Spaulding Rehabilitation Hospital, Tufts University, Charité, University of Zurich, Massachusetts Institute of Technology, and University of Massachusetts Medical School. Translating technological discoveries into commercial products and therapies is an important part of the organization's mission

Biology

https://en.wikipedia.org/wiki?curid=29017011

Wyss Institute for Biologically Inspired Engineering

Wyss Institute for Biologically Inspired Engineering The Wyss Institute’s scientific operations are organized around six Enabling Technology Platforms that focus on development of new core technologies and capabilities that will facilitate the explosion of major R&D areas in the field of bioinspired engineering. The platforms integrate multiple faculty members with the advanced technology team, clinical experts, and industrial partners. The Institute platforms are:

Biology

https://en.wikipedia.org/wiki?curid=29017011

Wyss Institute for Biologically Inspired Engineering

List of blindness effects There are several psychological and physiological effects that cause blindness to some visual stimulus.

Biology

https://en.wikipedia.org/wiki?curid=35671225

List of blindness effects

United States Marine Mammal Program The is an organization developed by the United States National Committee and the International Marine Mammal Working Group of the International Biological Program in 1969, for the study of marine mammals.

Biology

https://en.wikipedia.org/wiki?curid=35803896

United States Marine Mammal Program

Mir-616 microRNA precursor family mir-616 microRNA is a short non-coding RNA molecule belonging both to the family of microRNAs and to that of small interfering RNAs (siRNAs). MicroRNAs function to regulate the expression levels of other genes by several mechanisms, whilst siRNAs are involved primarily with the RNA interference (RNAi) pathway. miR-616 has been found to induce the specifically androgen-independent growth of prostate cancer cells. miR-616 overexpression has been observed in androgen-independent prostate cancer cells, specifically in malignant tissue compared with benign forms. It is notably resistant to castration in LNCaP cells, due to an enhanced ability to proliferate "in vivo". It has been found to interact with the tissue factor pathway inhibitor TFPI-2, and to directly target its mRNA at the three 3'UTR. Further, inhibition of TFPI-2 by miR-616 means inversely correlated expression of the two.

Biology

https://en.wikipedia.org/wiki?curid=36470616

Mir-616 microRNA precursor family

Xiyanping (喜炎平) is an anti-inflammatory and antiviral preparation developed and licensed for use in China. It is a semi-synthetic injectable product derived from the active component of the plant "Andrographis paniculata" (Chuan Xin Lian, 穿心蓮), which is used in Traditional Chinese medicine. is primarily composed of 9-dehydro-17-hydro-andrographolide and sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate. It is used mainly in the treatment of hand, foot and mouth disease, diarrhea, upper respiratory tract infections and viral pneumonia, though one case report suggested it may also be useful in the treatment of Zika fever. injection may be associated with side effects typical of allergic reaction, most commonly erythema and pruritus around the injection site, but more rarely anaphylactic reactions may occur, which can be life-threatening. Also, andrographolide and related derivatives are known to be abortifacient, making xiyanping unsuitable for use in pregnant women.

Biology

https://en.wikipedia.org/wiki?curid=49815805

Xiyanping

Epoxyeicosatetraenoic acid Epoxyeicosatetraenoic acids (EEQs or EpETEs) are a set of biologically active epoxides that various cell types make by metabolizing the omega 3 fatty acid, eicosapentaenoic acid (EPA), with certain cytochrome P450 epoxygenases. These epoxygenases can metabolize EPA to as many as 10 epoxides that differ in the site and/or stereoisomer of the epoxide formed; however, the formed EEQs, while differing in potency, often have similar bioactivities and are commonly considered together. EPA is a straight-chain, 20 carbon omega-3 fatty acid containing cis (see Cis–trans isomerism) double bonds between carbons 5 and 6, 8 and 9, 11 and 12, 14 and 15, and 17 and 18; each of these double bonds is designated with the notation "Z" to indicate its cis configuration in the IUPAC Chemical nomenclature used here. EPA is therefore 5"Z",8"Z",11"Z",14"Z",17"Z"-eicosapentaenoic acid. Certain cytochrome P450 epoxygenases metabolize EPA by converting one of these double bounds to an epoxide thereby forming one of 5 possible eicosatetraenoic acid epoxide regioisomers (see Structural isomer, section on position isomerism (regioisomerism)). These regioisomers are: 5,6-EEQ (i.e. 5,6-epoxy-8"Z",11"Z",14"Z",17"Z"-eicosatetraenoic acid), 8,9-EEQ (i.e. 8,9-epoxy-5"Z",11"Z",14"Z",17"Z"-eicosatetraenoic acid), 11,12-EEQ (i.e. 11,12-epoxy-5"Z",8"Z",14"Z",17"Z"-eicosatetraenoic acid), 14,15-EEQ (i.e. 14,15-epoxy-5"Z",8"Z",11"Z",17"Z"-eicosatetraenoic acid, and 17,18-EEQ (i.e. 17,18-epoxy-5"Z",8"Z",11"Z",14"Z"-eicosatetraenoic acid

Biology

https://en.wikipedia.org/wiki?curid=49854427

Epoxyeicosatetraenoic acid

Epoxyeicosatetraenoic acid The epoxydases typically make both "R"/"S" enantiomers of each epoxide. For example, they metabolize EPA at its 17,18 double bond to a mixture of 17"R",18"S"-EEQ and 17"S",18"R"-EEQ. The EEQ products therefore consist of as many as ten isomers. Cellular cytochrome P450 epoxygenases metabolize various polyunsaturated fatty acids to epoxide-containing products. They metabolize the omega-6 fatty acids arachidonic acid, which possess four double bonds, to 8 different epoxide isomers which are termed epoxyeicosatrienoic acids or EETs and linoleic acid, which possess two double bonds, to 4 different epoxide isomers, i.e. two different 9,10-epoxide isomers termed vernolic acids or leukotoxins and two different 12,13-epoxides isomers termed coronaric acids or isoleukotoxins. They metabolize the omega-3 fatty acid, docosahexaenoic acid, which possesses six double bonds, to twelve different epoxydocosapentaenoic acid (EDPs) isomers. In general, the same epoxygenases that accomplish these metabolic conversions also metabolize the omega-6 fatty acid, EPA, to 10 epoxide isomers, the EEQs. These epoxygenases fall into several subfamilies including the cytochrome P4501A (i.e.CYP1A), CYP2B, CYP2C, CYP2E, and CYP2J subfamilies, and within the CYP3A subfamily, CYP3A4. In humans, CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, CYP2J2, CYP3A4, and CYP2S1 metabolize EPA to EEQs, in most cases forming principally 17,18-EEQ with smaller amounts of 5,6-EEQ, 8,9-EEQ, 11,12-EEQ, and 14,15-EEQ isomers

Biology

https://en.wikipedia.org/wiki?curid=49854427

Epoxyeicosatetraenoic acid

Epoxyeicosatetraenoic acid However, CYP2C11, CYP2C18, and CYP2S1 also form 14,15-EEQ isomers while CYP2C19 also forms 11,12-EEQ isomers. The isomers formed by these CYPs vary greatly with, for example, the 17,18-EEQs made by CYP1A2 consisting of 17"R",18"S"-EEQ but no detectable 17"S",18"R"-EEQ and those made by CYP2D6 consisting principally of 17"R",18"S"-EEQ with far smaller amounts of 17"S",18"R"-EEQ. In addition to the cited CYP's, CYP4A11, CYP4F8, CYP4F12, CYP1A1, CYP1A2, and CYP2E1, which are classified as CYP monooxygenase rather than CYP epoxygeanses because they metablize arachidonic acid to monohydroxy eicosatetraenoic acid products (see 20-Hydroxyeicosatetraenoic acid), i.e. 19-hydroxyhydroxyeicosatetraenoic acid and/or 20-hydroxyeicosatetranoic acid, take on epoxygease activity in converting EPA primarily to 17,18-EEQ isomers (see epoxyeicosatrienoic acid). 5,6-EEQ isomers are generally either not formed or formed in undetectable amounts while 8,9-EEQ isomers are formed in relatively small amounts by the cited CYPs. The EET-forming CYP epoxygenases often metabolize EPA to EEQs (as well as DHA to EDPs) at rates that exceed their rates in metabolizing arachidonic acid to EETs; that is, EPA (and DHA) appear to be preferred over arachidonic acid as substrates for many CYP epoxygenases. The EEQ-forming cytochromes are widely distributed in the tissues of humans and other mammals, including blood vessel endothelium, blood vessel atheroma placques, heart muscle, kidneys, pancreas, intestine, lung, brain, monocytes, and macrophages

Biology

https://en.wikipedia.org/wiki?curid=49854427

Epoxyeicosatetraenoic acid

Epoxyeicosatetraenoic acid These tissues are known to metabolize arachidonic acid to EETs; it has been shown or is presumed that they also metabolize EPA to EEQs. Note, however, that the CYP epoxygenases, similar to essentially all CYP450 enzymes, are involved in the metabolism of xenobiotics as well as endogenously-formed compounds; since many of these same compounds also induce increases in the levels of the epoxygenases, CYP oxygenase levels and consequently EEQ levels in humans vary widely and are highly dependent on recent consumption history; numerous other factors, including individual genetic differences, also contribute to the variability in CYP450 epoxygenase expression. In cells, EEQs are rapidly metabolized by the same enzyme that similarly metabolizes other epoxy fatty acids including the EETs viz., cytosolic soluble epoxide hydrolase [EC 3.2.2.10.] (also termed sEH or the EPHX2), to form their corresponding Vicinal (chemistry) diol dihydroxyeicosatetraenoic acids (diHETEs). The omega-3 fatty acid epoxides, EEQs and EPAs, appear to be preferred over EETs as substates for sEH. sEH converts 17,18-EEQ isomers to 17,18-dihydroxy-eicosatrienoic acid isomers (17,18-diHETEs), 14,15-EEQ isomers to 14,15-diHETE isomers, 11,12-EEQ isomers to 11,12-diHETE isomers, 8,9-EEQ isomers to 8,9-diHETE isomers, and 5,6-EEQ isomers to 5,6-diHETE isomers. The product diHETEs, like their epoxy precursors, are enantiomer mixtures; for instance, sEH converts 17,18-EEQ to a mixture of 17("S"),19("R")-diHETE and 17("R"),18("S")-diHETE

Biology

https://en.wikipedia.org/wiki?curid=49854427

Epoxyeicosatetraenoic acid

Epoxyeicosatetraenoic acid Since the diHETE products are as a rule generally far less active than their epoxide precursors, the sEH pathway of EET metabolism is regarded as a critical EEQ-inactivating pathway. Membrane-bound Microsomal epoxide hydrolase (mEH or Epoxide hydrolase 2 [EC 3.2.2.9.]) can metabolize EEQs to their dihydroxy products but is regarded as not contributing significantly to EEQ inactivation in vivo except possibly in rare tissues where the sEH level is exceptionally low while the mEH level is high. In addition to the sEH pathway, EETs may be acylated into phospholipids in an Acylation-like reaction. This pathway may serve to limit the action of EETs or store them for future release. EETs are also inactivated by being further metabolized though three other pathways: Beta oxidation, Omega oxidation, and elongation by enzymes involved in Fatty acid synthesis. EEQS, similar to EDPs, have not be studied nearly as well as the EETs

Biology

https://en.wikipedia.org/wiki?curid=49854427

Epoxyeicosatetraenoic acid

Epoxyeicosatetraenoic acid In comparison to the many activities attributed to the EETs in animal model studies (see Epoxyeicosatrienoic acid), a limited set of studies indicate that EEQs (and EPAs) mimic EETS in their abilities to dilate arterioles, reduce hypertension, inhibit inflammation (the anti-inflammatory actions of EEQ are less potent than those of the EETs) and thereby reduce occlusion of arteries to protect the heart and prevent and strokes (see Epoxyeicosatrienoic acid#Clinical significance sections on a) Regulation of blood pressure, b) Heart disease, c) Strokes and seizures, and d) inflammation); they also mimic EETs in possessing analgesia properties in relieving certain types of pain (see Epoxyeicosatrienoic acid#Clinical significance#Pain). Often, the EEQs (and EPAs) exhibit greater potency and/or effectiveness than EET in these actions. In human studies potentially relevant to one or more of these activities, consumption of long chain omega-3 fatty acid (i.e. EPA- and DHA-rich) diet produced significant reductions in systolic blood pressure and increased peripheral arteriole blood flow and reactivity in patients at high to intermediate risk for cardiovascular events; an EPA/DHA-rich diet also reduced the risk while high serum levels of DHA and EPA were associated with a low risk of neovascular age-related macular degeneration

Biology

https://en.wikipedia.org/wiki?curid=49854427

Epoxyeicosatetraenoic acid

Epoxyeicosatetraenoic acid Since such diets lead to large increases in the serum and urine levels of EPAs, EEQs, and the dihydoxy metabolites of these epoxides but relatively little or no increases in EETs or lipoxygenase/cyclooxygenase-producing metabolites of arachidonic acid, DHA, and/or EEQs, it is suggested that the diet-induced increases in EPAs and/or EEQs are responsible for this beneficial effects. In direct contrast to the EETs which have stimulating effects in the following activities (see Epoxyeicosatrienoic acid#Cancer, EEQs (and EPAs) inhibit new blood vessel formation (i.e. angiogenesis), human tumor cell growth, and human tumor metastasis in animal models implanted with certain types of human cancer cells. The possible beneficial effects of omega-3 fatty acid-rich diets in pathological states involving inflammation, hypertension, blood clotting, heart attacks and other cardiac diseases, strokes, brain seizures, pain perception, acute kidney injury, and cancer are suggested to result, at least in part, from the conversion of dietary EPA and DHA to EEQs and EPAs, respectively, and the cited subsequent actions of these metabolites.

Biology

https://en.wikipedia.org/wiki?curid=49854427

Epoxyeicosatetraenoic acid

Merck Millipore was the brand used for Merck's global life science business until 2015 when the company re-branded. It was originally formed when Merck acquired the Millipore Corporation in 2010. Merck is a supplier to the life science industry. The Millipore Corporation was founded in 1954, and listed among the S&P 500 since the early 1990s, as an international biosciences company, known widely for its micrometer pore-size filters and tests. In 2015, Merck acquired Sigma-Aldrich and merged it with Merck Millipore. In the United States and Canada, the life science business is now known as MilliporeSigma. In the early 1950s Lovell Corporation won a contract from the U.S. Army Chemical Engineers to develop and manufacture membrane filtering devices and systems used to separate the molecular components of fluid samples. When the membranes were declassified in 1953 and offered for commercial use, Jack Bush, a Lovell employee, bought the company’s right to the technology for $200,000 and established the Millipore Filter Company. Bush coined the word millipore to use in the company's name to refer to large number of small openings in the microporous membrane that the company produced. At this point, however, "millipore" has become an actual word in general use apart from this company's use of it, referring to any of several filters, made from cellulose acetate membranes, capable of removing very small particles. Later the company changed its name to Millipore Corporation to reflect its growing range of products

Biology

https://en.wikipedia.org/wiki?curid=13025479

Merck Millipore

Merck Millipore In 2010, Merck KGaA the world's oldest chemical and pharmaceutical company- acquired Millipore Corporation to form EMD Millipore. By 1959, Millipore made porous membrane filters of cellulose esters or other materials which resembled paper in sheet form, and were brittle when dry but friable when wet. Filters consisted of nitrocellulose or polycarbonate membrane nucleopore filters ranging from pore size of 0.2 μm (micrometer) to 20 µm. Modern filter are Polyvinylidene fluoride and/or Polypropylene based. By 1970, Millipore had established subsidiaries in seven countries. The company opened manufacturing plants in Jaffrey, New Hampshire; Molsheim, France; Cork, Ireland; and several other locations. Millipore’s 2006 acquisition of Serologicals Corporation improved the company's position in high-growth markets such as drug discovery products and services, antibodies, cell biology reagents, and stem cell research. As of the late 2000s, Millipore was the only company providing both upstream cell culture and downstream separations offerings for biopharmaceutical production. Here are some of the key milestones representative of Millipore’s changes and growth over the past five decades. Millipore Corporation had been publicly traded on the OTC, or NASDAQ, exchange where it had paid a cash dividend to shareholders every year since 1966. In 1987 Millipore Corporation moved from the NASDAQ exchange to the New York Stock Exchange, where it traded under the ticker symbol MIL

Biology

https://en.wikipedia.org/wiki?curid=13025479

Merck Millipore

Merck Millipore Millipore Corporation was on the S&P 500 list of the biggest publicly traded companies in the United States until it was acquired by Merck kGaA in 2010. The deal was valued at approximately EUR 5.3 billion (US$7.2 billion). Merck KGaA is not associated with Merck & Co., although the two companies stem from the same parent company.

Biology

https://en.wikipedia.org/wiki?curid=13025479

Merck Millipore

Silent Spring is an environmental science book by Rachel Carson. The book was published on September 27, 1962, documenting the adverse environmental effects caused by the indiscriminate use of pesticides. Carson accused the chemical industry of spreading disinformation, and public officials of accepting the industry's marketing claims unquestioningly. Starting in the late 1950s, prior to the book's publication, Carson had focused her attention on environmental conservation, especially environmental problems that she believed were caused by synthetic pesticides. The result of her research was "Silent Spring", which brought environmental concerns to the American public. The book was met with fierce opposition by chemical companies, but, owing to public opinion, it brought about numerous changes. It spurred a reversal in the United States' national pesticide policy, led to a nationwide ban on DDT for agricultural uses, and helped to inspire an environmental movement that led to the creation of the U.S. Environmental Protection Agency. In 1996, a follow-up book, "Beyond Silent Spring", co-written by H.F. van Emden and David Peakall, was published. In 2006, "Silent Spring" was named one of the 25 greatest science books of all time by the editors of "Discover" magazine. In the mid-1940s, Carson became concerned about the use of synthetic pesticides, many of which had been developed through the military funding of science after World War II

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring The United States Department of Agriculture's 1957 fire ant eradication program, which involved aerial spraying of DDT and other pesticides mixed with fuel oil and included the spraying of private land, prompted Carson to devote her research, and her next book, to pesticides and environmental poisons. Landowners in Long Island filed a suit to have the spraying stopped, and many in affected regions followed the case closely. Though the suit was lost, the Supreme Court granted petitioners the right to gain injunctions against potential environmental damage in the future, laying the basis for later environmental actions. The impetus for "Silent Spring" was a letter written in January 1958 by Carson's friend, Olga Owens Huckins, to "The Boston Herald", describing the death of birds around her property resulting from the aerial spraying of DDT to kill mosquitoes, a copy of which Huckins sent to Carson. Carson later wrote that this letter prompted her to study the environmental problems caused by chemical pesticides. The Audubon Naturalist Society actively opposed chemical spraying programs and recruited Carson to help publicize the U.S. government's spraying practices and related research. Carson began the four-year project of "Silent Spring" by gathering examples of environmental damage attributed to DDT. She tried to enlist essayist E. B. White and a number of journalists and scientists to her cause. By 1958, Carson had arranged a book deal, with plans to co-write with "Newsweek" science journalist Edwin Diamond

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring However, when "The New Yorker" commissioned a long and well-paid article on the topic from Carson, she began considering writing more than the introduction and conclusion as planned; soon it became a solo project. Diamond would later write one of the harshest critiques of "Silent Spring". As her research progressed, Carson found a sizable community of scientists who were documenting the physiological and environmental effects of pesticides. She took advantage of her personal connections with many government scientists, who supplied her with confidential information on the subject. From reading the scientific literature and interviewing scientists, Carson found two scientific camps: those who dismissed the possible danger of pesticide spraying barring conclusive proof, and those who were open to the possibility of harm and, willing to consider alternative methods, such as biological pest control. By 1959, the USDA's Agricultural Research Service responded to the criticism by Carson and others with a public service film, "Fire Ants on Trial"; Carson called it "flagrant propaganda" that ignored the dangers that spraying pesticides posed to humans and wildlife. That spring, Carson wrote a letter, published in "The Washington Post", that attributed the recent decline in bird populationsin her words, the "silencing of birds"to pesticide overuse. The same year, the 1957, 1958, and 1959 crops of U.S

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring cranberries were found to contain high levels of the herbicide aminotriazole and the sale of all cranberry products was halted. Carson attended the ensuing FDA hearings on revising pesticide regulations; she was discouraged by the aggressive tactics of the chemical industry representatives, which included expert testimony that was firmly contradicted by the bulk of the scientific literature she had been studying. She also wondered about the possible "financial inducements behind certain pesticide programs". Research at the Library of Medicine of the National Institutes of Health brought Carson into contact with medical researchers investigating the gamut of cancer-causing chemicals. Of particular significance was the work of National Cancer Institute researcher and founding director of the environmental cancer section Wilhelm Hueper, who classified many pesticides as carcinogens. Carson and her research assistant Jeanne Davis, with the help of NIH librarian Dorothy Algire, found evidence to support the pesticide-cancer connection; to Carson the evidence for the toxicity of a wide array of synthetic pesticides was clear-cut, though such conclusions were very controversial beyond the small community of scientists studying pesticide carcinogenesis. By 1960, Carson had sufficient research material and the writing was progressing rapidly. She had investigated hundreds of individual incidents of pesticide exposure and the resulting human sickness and ecological damage

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring In January 1960, she suffered an illness which kept her bedridden for weeks, delaying the book. As she was nearing full recovery in March, she discovered cysts in her left breast, requiring a mastectomy. By December that year, Carson discovered that she had breast cancer, which had metastasized. Her research was also delayed by revision work for a new edition of "The Sea Around Us", and by a collaborative photo essay with Erich Hartmann. Most of the research and writing was done by the fall of 1960, except for a discussion of recent research on biological controls and investigations of some new pesticides. However, further health troubles delayed the final revisions in 1961 and early 1962. Its title was inspired by a poem by John Keats, "La Belle Dame sans Merci", which contained the lines "The sedge is wither'd from the lake, And no birds sing." "Silent Spring" was initially suggested as a title for the chapter on birds. By August 1961, Carson agreed to the suggestion of her literary agent Marie Rodell: "Silent Spring" would be a metaphorical title for the entire booksuggesting a bleak future for the whole natural worldrather than a literal chapter title about the absence of birdsong. With Carson's approval, editor Paul Brooks at Houghton Mifflin arranged for illustrations by Louis and Lois Darling, who also designed the cover. The final writing was the first chapter, "A Fable for Tomorrow", which was intended to provide a gentle introduction to a serious topic

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring By mid-1962, Brooks and Carson had largely finished the editing and were planning to promote the book by sending the manuscript to select individuals for final suggestions. In "Silent Spring", Carson relied on evidence from two New York state organic farmers, Marjorie Spock and Mary Richards, and that of biodynamic farming advocate Ehrenfried Pfeiffer in developing her case against DDT. The overarching theme of "Silent Spring" is the powerfuland often negativeeffect humans have on the natural world. Carson's main argument is that pesticides have detrimental effects on the environment; she says these are more properly termed "biocides" because their effects are rarely limited to the target pests. DDT is a prime example, but other synthetic pesticidesmany of which are subject to bioaccumulationare scrutinized. Carson accuses the chemical industry of intentionally spreading disinformation and public officials of accepting industry claims uncritically. Most of the book is devoted to pesticides' effects on natural ecosystems, but four chapters detail cases of human pesticide poisoning, cancer, and other illnesses attributed to pesticides. About DDT and cancer, Carson says only: Carson predicts increased consequences in the future, especially since targeted pests may develop resistance to pesticides and weakened ecosystems fall prey to unanticipated invasive species. The book closes with a call for a biotic approach to pest control as an alternative to chemical pesticides

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring Carson never called for an outright ban on DDT. She said in "Silent Spring" that even if DDT and other insecticides had no environmental side effects, their indiscriminate overuse was counterproductive because it would create insect resistance to pesticides, making them useless in eliminating the target insect populations: Carson also said that "Malaria programmes are threatened by resistance among mosquitoes", and quoted the advice given by the director of Holland's Plant Protection Service: "Practical advice should be 'Spray as little as you possibly can' rather than 'Spray to the limit of your capacity'. Pressure on the pest population should always be as slight as possible." Carson and the others involved with publication of "Silent Spring" expected fierce criticism and were concerned about the possibility of being sued for libel. Carson was undergoing radiation therapy for her cancer and expected to have little energy to defend her work and respond to critics. In preparation for the anticipated attacks, Carson and her agent attempted to amass prominent supporters before the book's release. Most of the book's scientific chapters were reviewed by scientists with relevant expertise, among whom Carson found strong support. Carson attended the White House Conference on Conservation in May 1962; Houghton Mifflin distributed proof copies of "Silent Spring" to many of the delegates and promoted the upcoming serialization in "The New Yorker"

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring Carson also sent a proof copy to Supreme Court Associate Justice William O. Douglas, a long-time environmental advocate who had argued against the court's rejection of the Long Island pesticide spraying case and had provided Carson with some of the material included in her chapter on herbicides. Though "Silent Spring" had generated a fairly high level of interest based on pre-publication promotion, this became more intense with its serialization, which began in the June 16, 1962, issue. This brought the book to the attention of the chemical industry and its lobbyists, as well as the American public. Around that time, Carson learned that "Silent Spring" had been selected as the Book-of-the-Month for October; she said this would "carry it to farms and hamlets all over that country that don't know what a bookstore looks likemuch less "The New Yorker"." Other publicity included a positive editorial in "The New York Times" and excerpts of the serialized version were published in "Audubon Magazine". There was another round of publicity in July and August as chemical companies responded. The story of the birth defect-causing drug thalidomide had broken just before the book's publication, inviting comparisons between Carson and Frances Oldham Kelsey, the Food and Drug Administration reviewer who had blocked the drug's sale in the United States. In the weeks before the September 27, 1962, publication, there was strong opposition to "Silent Spring" from the chemical industry

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring DuPont, a major manufacturer of DDT and 2,4-D, and Velsicol Chemical Company, the only manufacturer of chlordane and heptachlor, were among the first to respond. DuPont compiled an extensive report on the book's press coverage and estimated impact on public opinion. Velsicol threatened legal action against Houghton Mifflin, and "The New Yorker" and "Audubon Magazine" unless their planned "Silent Spring" features were canceled. Chemical industry representatives and lobbyists lodged a range of non-specific complaints, some anonymously. Chemical companies and associated organizations produced brochures and articles promoting and defending pesticide use. However, Carson's and the publishers' lawyers were confident in the vetting process "Silent Spring" had undergone. The magazine and book publications proceeded as planned, as did the large Book-of-the-Month printing, which included a pamphlet by William O. Douglas endorsing the book. American Cyanamid biochemist Robert White-Stevens and former Cyanamid chemist Thomas Jukes were among the most aggressive critics, especially of Carson's analysis of DDT. According to White-Stevens, "If man were to follow the teachings of Miss Carson, we would return to the Dark Ages, and the insects and diseases and vermin would once again inherit the earth". Others attacked Carson's personal character and scientific credentials, her training being in marine biology rather than biochemistry

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring White-Stevens called her "a fanatic defender of the cult of the balance of nature", while former U.S. Secretary of Agriculture Ezra Taft Benson in a letter to former President Dwight D. Eisenhower reportedly said that because she was unmarried despite being physically attractive, she was "probably a Communist". Monsanto published 5,000 copies of a parody called "The Desolate Year" (1962) which projected a world of famine and disease caused by banning pesticides. Many critics repeatedly said Carson was calling for the elimination of all pesticides, but she had made it clear she was not advocating this but was instead encouraging responsible and carefully managed use with an awareness of the chemicals' impact on ecosystems. She concludes her section on DDT in "Silent Spring" with advice for spraying as little as possible to limit the development of resistance. Mark Hamilton Lytle writes, Carson "quite self-consciously decided to write a book calling into question the paradigm of scientific progress that defined postwar American culture". The academic communityincluding prominent defenders such as H. J. Muller, Loren Eiseley, Clarence Cottam and Frank Eglermostly backed the book's scientific claims and public opinion backed Carson's text. The chemical industry campaign was counterproductive because the controversy increased public awareness of the potential dangers of pesticides, an early example of the Streisand Effect

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring Pesticide use became a major public issue after a "CBS Reports" television special, "The of Rachel Carson", which was broadcast on April 3, 1963. The program included segments of Carson reading from "Silent Spring" and interviews with other experts, mostly critics including White-Stevens. According to biographer Linda Lear, "in juxtaposition to the wild-eyed, loud-voiced Dr. Robert White-Stevens in white lab coat, Carson appeared anything but the hysterical alarmist that her critics contended". Reactions from the estimated audience of ten to fifteen million were overwhelmingly positive and the program spurred a congressional review of pesticide hazards and the public release of a pesticide report by the President's Science Advisory Committee. Within a year of publication, attacks on the book and on Carson had lost momentum. In one of her last public appearances, Carson testified before President John F. Kennedy's Science Advisory Committee, which issued its report on May 15, 1963, largely backing Carson's scientific claims. Following the report's release, Carson also testified before a U.S. Senate subcommittee to make policy recommendations. Though Carson received hundreds of other speaking invitations, she was unable to accept most of them because her health was steadily declining, with only brief periods of remission. She spoke as much as she could, and appeared on "The Today Show" and gave speeches at several dinners held in her honor

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring In late 1963, she received a flurry of awards and honors: the Audubon Medal from the National Audubon Society, the Cullum Geographical Medal from the American Geographical Society, and induction into the American Academy of Arts and Letters. The book was translated into German (under the title: "Der stumme Frühling"), with the first German edition appearing in 1963, followed by a number of later editions. It was translated into French (as "Printemps silencieux"), with the first French edition also appearing in 1963. In 1964 the book was translated into Dutch (as "Dode lente"), according to Worldcat.org the second edition was published in 1962. In 1965 "Silent Spring" was published in USSR in Russian (under the title ""). The book's Italian title is "Primavera silenziosa".; and the Spanish title is "Primavera silenciosa". It was translated to Swedish and published in 1963, titled "Tyst vår". In Finland the largest subscription newspaper, Helsingin Sanomat (Helsinki times/news), published parts of the book in an 8-part article series in 1962. That same year it was published by publishing company Tammi, with the title "Äänetön kevät". It was translated to Chinese and published in 1979, titled "寂静的春天". Carson's work had a powerful impact on the environmental movement. "Silent Spring" became a rallying point for the new social movement in the 1960s. According to environmental engineer and Carson scholar H. Patricia Hynes, ""Silent Spring" altered the balance of power in the world

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring No one since would be able to sell pollution as the necessary underside of progress so easily or uncritically." Carson's work and the activism it inspired are partly responsible for the deep ecology movement and the strength of the grassroots environmental movement since the 1960s. It was also influential on the rise of ecofeminism and on many feminist scientists. Carson's most direct legacy in the environmental movement was the campaign to ban the use of DDT in the United States, and related efforts to ban or limit its use throughout the world. The 1967 formation of the Environmental Defense Fund was the first major milestone in the campaign against DDT. The organization brought lawsuits against the government to "establish a citizen's right to a clean environment", and the arguments against DDT largely mirrored Carson's. By 1972, the Environmental Defense Fund and other activist groups had succeeded in securing a phase-out of DDT use in the United States, except in emergency cases. The creation of the Environmental Protection Agency by the Nixon Administration in 1970 addressed another concern that Carson had written about. Until then, the USDA was responsible both for regulating pesticides and promoting the concerns of the agriculture industry; Carson saw this as a conflict of interest, since the agency was not responsible for effects on wildlife or other environmental concerns beyond farm policy. Fifteen years after its creation, one journalist described the EPA as "the extended shadow of "Silent Spring""

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring Much of the agency's early work, such as enforcement of the 1972 Federal Insecticide, Fungicide, and Rodenticide Act, was directly related to Carson's work. Contrary to the position of the pesticide industry, the DDT phase-out action taken by the EPA (led by William Ruckelshaus) implied that there was no way to adequately regulate DDT use. Ruckelshaus' conclusion was that DDT could not be used safely. History professor Gary Kroll wrote, "Rachel Carson's "Silent Spring" played a large role in articulating ecology as a 'subversive subject'as a perspective that cuts against the grain of materialism, scientism, and the technologically engineered control of nature." In a 2013 interview, Ruckelshaus briefly recounted his decision to ban DDT except for emergency uses, noting that Carson's book featured DDT and for that reason the issue drew considerable public attention. Former Vice President of the United States and environmentalist Al Gore wrote an introduction to the 1992 edition of "Silent Spring". He wrote: ""Silent Spring" had a profound impact ... Indeed, Rachel Carson was one of the reasons that I became so conscious of the environment and so involved with environmental issues  ...  [she] has had as much or more effect on me than any, and perhaps than all of them together

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring " Carson has been targeted by some organizations opposed to the environmental movement, including Roger Bate of the pro-DDT advocacy group Africa Fighting Malaria and the libertarian think tank Competitive Enterprise Institute; these sources oppose restrictions on DDT, attribute large numbers of deaths to such restrictions, and argue that Carson was responsible for them. These arguments have been dismissed as "outrageous" by former WHO scientist Socrates Litsios. May Berenbaum, University of Illinois entomologist, says, "to blame environmentalists who oppose DDT for more deaths than Hitler is worse than irresponsible." Investigative journalist Adam Sarvana and others characterize this notion as a "myth" promoted principally by Roger Bate of the pro-DDT advocacy group Africa Fighting Malaria (AFM). In the 2000s, criticism of the bans of DDT that her work prompted intensified. In 2009, the heavily corporate-funded libertarian think tank Competitive Enterprise Institute set up a website saying, "Millions of people around the world suffer the painful and often deadly effects of malaria because one person sounded a false alarm. That person is Rachel Carson." This triggered a point-by-point rebuttal by biographer William Souder, who reviewed the distortions used by campaigners against "Silent Spring"

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring A 2012 review article in "Nature" by Rob Dunn commemorating the 50th anniversary of "Silent Spring" and summarizing the progressive environmental-policy changes made since then, prompted a response in a letter written by Anthony Trewavas and co-signed by 10 others, including Christopher Leaver, Bruce Ames, Richard Tren and Peter Lachmann, who quote estimates of 60 to 80 million deaths "as a result of misguided fears based on poorly understood evidence". Biographer Hamilton Lytle believes these estimates are unrealistic, even if Carson can be "blamed" for worldwide DDT policies. John Quiggin and Tim Lambert wrote, "the most striking feature of the claim against Carson is the ease with which it can be refuted". DDT was never banned for anti-malarial use, and its ban for agricultural use in the United States in 1972 did not apply outside the U.S. nor to anti-malaria spraying. The international treaty that banned most uses of DDT and other organochlorine pesticidesthe 2001 Stockholm Convention on Persistent Organic Pollutants (which became effective in 2004)included an exemption for the use of DDT for malaria control until affordable substitutes could be found. Mass outdoor spraying of DDT was abandoned in poor countries subject to malaria, such as Sri Lanka, in the 1970s and 1980s; this was not because of government prohibitions but because the DDT had lost its ability to kill the mosquitoes

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring Because of insects' very short breeding cycle and large number of offspring, the most resistant insects survive and pass on their genetic traits to their offspring, which replace the pesticide-slain insects relatively rapidly. Agricultural spraying of pesticides produces pesticide resistance in seven to ten years. Some experts have said that restrictions placed on the agricultural use of DDT have increased its effectiveness for malaria control. According to pro-DDT advocate Amir Attaran, the result of the (activated in 2004) Stockholm Convention banning DDT's use in agriculture "is arguably better than the status quo ... For the first time, there is now an insecticide which is restricted to vector control only, meaning that the selection of resistant mosquitoes will be slower than before." "Silent Spring" has been featured in many lists of the best nonfiction books of the twentieth century. It was fifth in the Modern Library List of Best 20th-Century Nonfiction and number 78 in the "National Review's" 100 best non-fiction books of the 20th century. In 2006, "Silent Spring" was named one of the 25 greatest science books of all time by the editors of "Discover Magazine". In 2012, the American Chemical Society designated the legacy of "Silent Spring" a National Historic Chemical Landmark at Chatham University in Pittsburgh. In 1996, a follow-up book, "Beyond Silent Spring", co-written by H.F. van Emden and David Peakall, was published

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

Silent Spring In 2011, the American composer Steven Stucky wrote the eponymously titled symphonic poem "Silent Spring" to commemorate the fiftieth anniversary of the book's publication. The piece was given its world premiere in Pittsburgh on February 17, 2012, with the conductor Manfred Honeck leading the Pittsburgh Symphony Orchestra. Naturalist Sir David Attenborough has stated that "Silent Spring" was probably the book that had changed the scientific world the most, after the "Origin of Species" by Charles Darwin.

Biology

https://en.wikipedia.org/wiki?curid=81283

Silent Spring

MethBase is a database of DNA methylation data derived from next-generation sequencing data. provides a visualization of publicly available bisulfite sequencing and reduced representation bisulfite sequencing experiments through the UCSC Genome Browser. contents include single-CpG site resolution methylation levels for each CpG site in the genome of interest, annotation of regions of hypomethylation often associated with gene promoters, and annotation of allele-specific methylation associated with genomic imprinting.

Biology

https://en.wikipedia.org/wiki?curid=52439884

MethBase

Erdafitinib is a small molecule inhibitor of fibroblast growth factor receptor (FGFR) approved for treatment of cancer and marketed under the name Balversa. FGFRs are a subset of tyrosine kinases which are unregulated in some tumors and influence tumor cell differentiation, proliferation, angiogenesis, and cell survival. Astex Pharmaceuticals discovered the drug and licensed it to Janssen Pharmaceuticals for further development. Researchers have investigated erdafitinib for safety and efficacy in treatment of bile duct cancer, gastric cancer, non-small cell lung cancer, and esophageal cancer. In March 2018, erdafitinib was granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) for treatment of urothelial cancer. In April 2019, erdafitinib was granted approval by the FDA for treatment of metastatic or locally advanced bladder cancer with an FGFR3 or FGFR2 alteration that has progressed beyond traditional platinum-based therapies, subject to a confirmatory trial. is a tablet taken once a day for a total dose of 8mg. During treatment, the erdafitinib dose may be increased to 9mg if needed. Common side effects include increased phosphate level, mouth sores, feeling tired, change in kidney function, diarrhea, dry mouth, nails separating from the bed or poor formation of the nail, change in liver function, low salt (sodium) levels, decreased appetite, change in sense of taste, low red blood cells (anemia), dry skin, dry eyes and hair loss

Biology

https://en.wikipedia.org/wiki?curid=53048111

Erdafitinib

Erdafitinib Other side effects include redness, swelling, peeling or tenderness on the hands or feet (hand foot syndrome), constipation, stomach pain, nausea and muscle pain. may cause serious eye problems, including inflamed eyes, inflamed cornea (front part of the eye) and disorders of the retina, an internal part of the eye. Patients are advised to have eye examinations intermittently and to tell their health care professional right away if they develop blurred vision, loss of vision or other visual changes. The efficacy of erdafitinib was studied in a clinical trial (NCT02365597) that included 87 adults with locally advanced or metastatic bladder cancer, with FGFR3 or FGFR2 genetic alterations, that had progressed following treatment with chemotherapy. The overall response rate in these adults was 32.2%, with 2.3% having a complete response and almost 30% having a partial response. The response lasted for an average of approximately five-and-a-half months. The trial was conducted in Asia, Europe, and the United States. received an accelerated approval. Further clinical trials are required to confirm erdafitinib's clinical benefit and the sponsor is conducting or plans to conduct these studies. was also granted breakthrough therapy designation. The FDA granted the approval of Balversa to Janssen Pharmaceutical. The FDA also approved the therascreen FGFR RGQ RT-PCR Kit, developed by Qiagen Manchester, Ltd., for use as a companion diagnostic with Balversa for this therapeutic indication.

Biology

https://en.wikipedia.org/wiki?curid=53048111

Erdafitinib

National Catholic Bioethics Center The is a research center located in Philadelphia, Pennsylvania. Established in 1972, its mission is promoting and safeguarding the dignity of the human person, thereby sharing in the ministry of Jesus Christ and his Church. The chairman of the Board of Directors is the Most Reverend Robert C. Morlino, bishop of Madison, Wisconsin. The Center publishes "Ethics & Medics" and "The National Catholic Bioethics Quarterly", as well as books, including the "Handbook on Critical Life Issues". The founding president of the Center was the Rev. Albert S. Moraczewski, O.P. A library, named in his honor, was dedicated in 2007. The current president, who was named by Pope Benedict XVI in June 2010 as a member of the Pontifical Academy for Life, is John M. Haas, Ph.D. The staff of six professional ethicists responds to over 600 requests each year for advice on moral issues of concern to Catholics and other interested parties via e-mail, phone, and letter. The Center also provides moral analysis to the offices of the United States Conference of Catholic Bishops (USCCB) and to the dicastries of the Holy See. In a 1999 article of "Ethics and Medics", it was argued that "as parents have a moral obligation to secure the life and health of their children", so too do they "have a moral obligation to provide vaccinations to their children." The departments of the Center include education, publications, research and public policy

Biology

https://en.wikipedia.org/wiki?curid=11084424

National Catholic Bioethics Center

National Catholic Bioethics Center The educational department administers "The National Catholic Certification Program in Health Care Ethics", a year-long distance learning program that educates candidates in the fundamentals of Catholic medical-moral teaching, with special emphasis on the application of the "Ethical and Religious Directives for Catholic Health Care Services," a document of the USCCB designed to guide Catholic health care institutions.

Biology

https://en.wikipedia.org/wiki?curid=11084424

National Catholic Bioethics Center

Eyespot (mimicry) An eyespot (sometimes ocellus) is an eye-like marking. They are found in butterflies, reptiles, cats, birds and fish. Eyespots may be a form of mimicry in which a spot on the body of an animal resembles an eye of a different animal to deceive potential predator or prey species; a form of self-mimicry, to draw a predator's attention away from the most vulnerable body parts; or to appear as an inedible or dangerous animal. Eyespots may play a role in intraspecies communication or courtship; the best-known example is probably the eyespots on a peacock's display feathers. Eyespots are not necessarily adaptations, but may in some cases be spandrels, accidental artifacts of pattern formation. The morphogenesis of eyespots is controlled by a small number of genes active in embryonic development of a wide range of animals, including Engrailed, Distal-less, Hedgehog, Antennapedia, and the Notch signaling pathway. The eye-like markings in some butterflies and moths, like the "Bicyclus anynana," and certain other insects, as well as the sunbittern (a bird) do not seem to serve only a mimicry function. In some other cases, the evolutionary function of such spots is also not understood. There is evidence that eyespots in butterflies are antipredator adaptations, either in deimatic displays to intimidate predators, or to deflect attacks away from vital body parts

Biology

https://en.wikipedia.org/wiki?curid=11615271

Eyespot (mimicry)

Eyespot (mimicry) In some species, such as "Hipparchia semele", the conspicuous eyespots are hidden at rest to decrease detectability, and only exposed when they believe potential predators are nearby. Butterfly eyespots may also play a role in mate recognition and sexual selection. Some species of caterpillar, such as many hawkmoths (Sphingidae), have eyespots on their anterior abdominal segments. When alarmed, they retract the head and the thoracic segments into the body, leaving the apparently threatening large eyes at the front of the visible part of the body. Many butterflies such as the blues (Lycaenidae) have filamentous "tails" at the ends of their wings and nearby patterns of markings on the wings, which combine to create a "false head". This automimicry misdirects predators such as birds and jumping spiders (Salticidae). Spectacular examples occur in the hairstreak butterflies; when perching on a twig or flower, they commonly do so upside down and shift their rear wings repeatedly, causing antenna-like movements of the "tails" on their wings. Studies of rear-wing damage support the hypothesis that this strategy is effective in deflecting attacks from the insect's head. Some reptiles, such as the sand lizard of Europe, have eyespots; in the sand lizard's case, there is a row of spots along the back, and a row on each side. Male birds of some species, such as the peacock, have conspicuous eyespots in their plumage, used to signal their quality to sexually selecting females

Biology

https://en.wikipedia.org/wiki?curid=11615271

Eyespot (mimicry)

Eyespot (mimicry) The number of eyespots in a peacock's train predicts his mating success; when a peacock's train is experimentally pruned, females lose interest. Several species of pygmy owl bear false eyes on the back of the head, misleading predators into reacting as though they were the subject of an aggressive stare. Some fish have eyespots. The foureye butterflyfish gets its name from a large and conspicuous eyespot on each side of the body near the tail. A black vertical bar on the head runs through the true eye, making it hard to see. This may deceive predators into attacking the tail rather than the more vulnerable head, and about the fish's likely direction of travel: in other words, the eyespot is an example of self-mimicry. For the same reason, many juvenile fish display eyespots that disappear during their adult phase. Some species of fish, like the spotted mandarin fish and spotted ray, maintain their eyespots throughout their adult lives. These eyespots can take a form very similar to those seen in most butterflies, with a focus surrounded by concentric rings of other pigmentation. Butterfly eyespots are formed during embryogenesis as a result of a morphogenetic signaling center or organizer, called the focus. This induces neighboring cells to produce specific pigments which pattern the eyespot. Early experiments on eyespot morphogenesis used cautery on the butterfly wing eyespot foci to demonstrate that a long range signaling mechanism or morphogen gradient controlled eyespot formation in both space and time

Biology

https://en.wikipedia.org/wiki?curid=11615271

Eyespot (mimicry)

Eyespot (mimicry) The findings cannot be explained by a simple source/diffusion model, but could be explained by either 1) A source/threshold model, in which the focus creates the morphogen, or 2) the sink model, in which the focus generates a gradient by removing a morphogen which was created elsewhere. Several genes involved in eyespot formation have been identified that can fit into these models, but only two of them have been functionally tested. These genes are the transcription factor Distalless (Dll) and the ligand (a signaling substance that binds a cell surface receptor) Hedgehog (Hh). Butterfly eyespot morphology appears to be the result of the evolution of an altered version of the regulatory circuit which patterns the wings of other insects. This rogue regulatory circuit is able to pattern both the anterior and posterior eyespots independent of the usual anterior/posterior wing compartmentalization restrictions seen in the fruit fly "Drosophila". The altered regulatory circuit redeploys early developmental signaling sources, like the canonical hedgehog (Hh) pathway, Distal-less (Dll), and engrailed (En), breaking the anterior/posterior compartmentalization restrictions through increased localized levels of Hh signaling. In turn, this raises expression of its receptor Patched (Ptc) and transcription factor

Biology

https://en.wikipedia.org/wiki?curid=11615271

Eyespot (mimicry)

Eyespot (mimicry) Normally, in "Drosophila", engrailed acts in the posterior compartment to restrict Ptc and "Cubitus interruptus" (Ci) expression to the anterior compartment by repressing transcription of Ci, thereby preventing Ptc expression. From the perspective of evolutionary developmental biology, understanding the redeployment and plasticity of existing regulatory mechanisms in butterfly eyespot locus development has given more insight into a fundamental mechanism for the evolution of novel structures. The Distal-less gene is present in almost all eyespot organizers, making it an ideal candidate to carry out major functions of eyespot formation. During the wing imaginal disc development Dll, has two expression domains separated by a temporal component. First Dll is expressed in a group of cells in the center of what will become the focus and eventually the eyespot. This expression starts during the middle of the fifth instar larva and lasts until the pupal stage. The second domain starts around 20 hours after pupation around the original central cluster of cells, in an area in which a black ring of the eyespot will be formed. Functional experiments using transgenic "Bicyclus anynana" (the squinting bush brown butterfly) have shown that overexpression or down-regulation of Dll in the first expression domain correlates with bigger and smaller eyespots respectively

Biology

https://en.wikipedia.org/wiki?curid=11615271

Eyespot (mimicry)

Eyespot (mimicry) However, if this is done on the second domain then the overall size of the eyespots remains the same, but the width of the black ring raises with a higher amount of Dll. This suggests that Dll might be responsible for the differentiation of the focus in the first expression domain and might be involved in establishing the ring color patterns in the second domain. These experiments together with the wide distribution of Dll across eyespot forming butterflies suggest that this transcription factor is a central regulator for the correct patterning of the eyespots. The Hh gene is the other element that has been functionally tested in the formation of eyespots. Investigating genes involved in wing development and morphogenetic activity has led to the discovery that Hh has a primary role in the morphogenetic signaling center of the foci. In a manner that is similar to the development of "Drosophila" fruit flies, Hh is expressed in all cells in the posterior compartment of the developing butterfly wing during the mid fifth instar of butterfly wing development. However, in butterflies, Hh expression is significantly higher in those cells that flank the potential foci. Higher transcription levels of Hh, along with other known associates of the Hh pathway, namely patched (Ptc) the Hh receptor, and cubitus interruptus (Ci), the Hh transcription factor is seen throughout the mid to late fifth instar as well, which further implies a role for Hh signaling in eyespot development and patterning

Biology

https://en.wikipedia.org/wiki?curid=11615271

Eyespot (mimicry)

Eyespot (mimicry) Furthermore, cells that are flanked by the cells expressing the highest level of Hh signaling are fated to become the foci, indicating that focus cell fate determination relies on high concentrations of Hh in surrounding cells. However this observation has not been totally confirmed as a rule for multiple butterfly species. Studies tried to extrapolate the result of Hh pathway involvement by looking for the expression of Ci in "Bicyclus anynana". Here they observed that both seem to be expressed in eyespots, suggesting a relation with the Hh signaling pathway. However, other studies did not find evidence of Hh expression in "B. anynana". The Notch (N) gene expression precedes an upregulation of Dll in the cells that will become the center of the focus. This makes N the earliest developmental signal, so far studied, that is related with the establishment of the eyespots. Loss of N completely disrupts Dll expression, and eventually eyespot formation, in several butterfly species. A variety of other wing patterns are determined by N and Dll patterns of expression in early development of the wing imaginal disc, suggesting that a single mechanism patterns multiple coloration structures of the wing.

Biology

https://en.wikipedia.org/wiki?curid=11615271

Eyespot (mimicry)