text
stringlengths 9
5.77M
| timestamp
stringlengths 26
26
| url
stringlengths 32
32
|
|---|---|---|
HAVRE DE GRACE, Md. Troopers recovered thousands of dollars worth of cocaine from the trunk of a car in which two men were killed early this morning after the driver fled from a trooper trying to stop him on I-95 in Harford County.
The driver was identified as Charles L. Quinones, Jr., 37, of the 5200-block of Cromarty Road, Baltimore, Md. During the crash investigation, troopers found Quinones was wanted on a felony warrant in Baltimore County for failure to appear for a charge of possession with intent to distribute cocaine. Troopers also found his drivers license had been suspended in Maryland for more than one year.
The passenger was identified as Willie S. Robertson, 74, of the 1000-block of Jeanette Way, Bel Air, Md. The 2005 Mercury Sable Quinones was driving was registered to Robertson.
Shortly after 5:00 a.m. today, a trooper assigned to the State Police Pro-Active Criminal Enforcement Team was working patrol on southbound I-95 south of Rt. 272 when he observed the Mercury headed in the same direction. The trooper saw that the rear license plate was obstructed and determined the vehicle was traveling 72 mph in a posted 65 mph zone.
Approaching the Rt. 222 interchange, the trooper activated his lights and siren on his marked Ford Expedition State Police patrol vehicle. The driver of the Mercury, later identified as Quinones, signaled he was pulling over, then quickly swerved to the fast lane and accelerated.
Quinones continued south on I-95 driving aggressively as he weaved between vehicles. The pursuing trooper was traveling at 90 mph, but was unable to keep up with the fleeing Mercury. The trooper was about one-half mile behind as he approached the Rt. 155 exit and saw the Mercury swerve across several lanes, cut off a tractor trailer, and take the ramp to westbound Rt. 155.
The trooper took the exit ramp and, near the end of the ramp about one-quarter mile off I-95, found the Mercury had gone off the eastbound side of Rt. 155 and crashed into trees not far from the shoulder of the road. The trooper and other responding troopers attempted to render aid to the two men and called for a State Police helicopter and an ambulance. Medics who arrived at the scene pronounced the men dead.
Witnesses told troopers the driver of the Mercury was passing cars on the right as it came off Rt. 155 at a high rate of speed. They said the driver then lost control, swerved across the highway and crashed.
A police search of the heavily damaged car found six and one-half ounces of powder cocaine in plastic bags in the trunk. State Police drug investigators estimate the cocaine could have been sold on the street for more than $18,000.
The crash is being investigated by the Maryland State Police CRASH Team. A detailed crash reconstruction will be conducted. The investigation is continuing. | 2024-01-24T01:26:28.774034 | https://example.com/article/9325 |
Q:
Symfony 2 kpn snappy generate pdf with output meets security area
I`m using Symfony2 kpn snappy bundle to generate pdfs. I want to generate PDF from an html page with css. I found a solution, but it has a problem with :
$pageUrl = $this->generateUrl('accounts_management_generate_pdf_markup',
array('invoice' => $invoiceData), true); // use absolute path!
return new \Symfony\Component\HttpFoundation\Response(
$this->get('knp_snappy.pdf')->getOutput($pageUrl), 200, array(
'Content-Type' => 'application/pdf',
'Content-Disposition' => 'attachment; filename="file.pdf"'
)
);
The problem is that the pageUrl accounts_management_generate_pdf_markup is behind a security area and cannot be accessed without authentication. The generated file is just the login page, to which this path accounts_management_generate_pdf_markup redirects if not logged.
My questions are:
Is there any way to pass to snappy authentication credentials?
Is there another way using snappy bundle to generate the pdf using styles(css)
A:
You can add the session cookie as an argument to the getOutput function:
$pageUrl = $this->generateUrl('route', array('id' => $id), true);
$session = $this->get('session');
$session->save();
session_write_close();
return new Response(
$this->get('knp_snappy.pdf')->getOutput($pageUrl, array('cookie' => array($session->getName() => $session->getId()))),
200,
array(
'Content-Type' => 'application/pdf',
'Content-Disposition' => 'attachment; filename="file.pdf"'
)
);
| 2024-07-08T01:26:28.774034 | https://example.com/article/4272 |
Blog Categories
Category: Mesothelioma
Have you or has someone you love recently been diagnosed with mesothelioma? Looking for pertinent, key facts on the disease? This article, Mesothelioma for Dummies, will answer your most fundamental questions on what the disease is, who is at risk, treatment options, and where to turn for legal help.
One of the most important mesothelioma facts to know is this: Exposure to asbestos is the primary cause of this rare form of cancer. Asbestos is a fibrous material used mainly in construction, especially during the 20th century. However, even after they were discovered to be hazardous, asbestos companies continued to make products containing this toxic material because of their strength and resistance to heat.
Who’s at the Greatest Risk for Mesothelioma?
Mesothelioma is a disease largely caused by occupational exposure. Some of the occupations most at risk include electricians, carpenters, machinists, plumbers, boilermakers, and military personnel. Additionally, family members of employees who worked in power plants, refineries, steel mills, construction sites, and Navy ships could be at risk for secondhand exposure. It is unknown how many people get mesothelioma from second hand exposure, but it is contracted from the dust brought home on clothing, hair, or skin.
A large majority of victims of mesothelioma are veterans of our country’s armed forces who served from 1930 through 1980. Asbestos was commonly used throughout shipyards and naval vessels during those years. Asbestos was an effective and inexpensive way to safeguard sailors from fire, heat, and electrical shock. It was also used in sleeping quarters, engine rooms, and mess halls as insulation.
Mesothelioma for Dummies: The Disease
Mesothelioma can be difficult to diagnose, as the symptoms can mirror those of many other illnesses. An early mesothelioma diagnoses is difficult but can happen accidently through a routine x-ray or blood test. If you have been exposed to asbestos, watch for the symptoms and notify your doctor of your risk for mesothelioma.
What are the Symptoms of Mesothelioma?
The early signs of mesothelioma can be mistaken for indigestion, pneumonia, bronchitis, or even the flu. The growth of the cancerous tumors occurs gradually, and sometimes it takes decades for the symptoms to even present themselves. As a result, mesothelioma statistics show that by the time the cancer is diagnosed, it has reached the later stages of development. By recognizing symptoms immediately, mesothelioma patients have a significant advantage in receiving an early diagnosis, which can determine the best course of action for prolonged life expectancy.
Pleural Mesothelioma (occurs in lining of the lung)
Fatigue
Coughing
Shortness of breath
Chest pain
Fever/night sweats
Peritoneal (occurs in lining of abdomen)
Nausea
Fever
Weight loss
Loss of appetite
Bloating
Pericardial (occurs in lining of the heart)
Chest pain
Fever/night sweats
Shortness of breath
Irregular heartbeat
Coughing
What are the Treatment Options for Mesothelioma?
Despite years of research, no cure currently exists for mesothelioma. However, there are treatments that can improve a patient’s prognosis and quality of life. The most common treatment for mesothelioma is a combination of surgery, chemotherapy, and radiation.
Many people choose to also pursue alternative therapies for mesothelioma treatment including:
Immunotherapy-assists a patient’s own immune system in fighting the cancer
Gene therapy-injects genetic material into the body to target and kill the cancer cells
Mesothelioma for Dummies: Your Legal Options
Mesothelioma patients and their families deserve justice and financial compensation for their pain and suffering. While reading our article about Mesothelioma for Dummies is a great starting point, finding a lawyer who is familiar with asbestos laws and the disease itself is critical. The attorneys at the Nemeroff Law Firm have the dedication, compassion, and experience you are looking for. They will fight hard to ensure you receive the compensation you deserve. Don’t wait, contact us today at 866-342-1929 or by email.
Many companies that do not comply with standard health precautions may expose workers to cancerous materials such as asbestos. This material is the predominant cause of mesothelioma cancer, a sly disease that only shows its effects decades after exposure. If you or a loved one have been exposed to cancerous asbestos, consider organizing a mesothelioma screening to stay one step ahead of your health.
How Does a Mesothelioma Screening Work?
The first step to your diagnostic process is seeing a qualified physician who will conduct a physical examination and ask about your medical history and possible exposure to asbestos particles. If there are mesothelioma symptoms or other troubling signs, the physician may encourage further testing.
Who Should Consider a Mesothelioma Screening?
Mesothelioma cancer is very rare, generally found in those exposed to asbestos for a long time, such as firefighters, carpenters, asbestos miners, and construction workers. These occupations are at a higher risk for asbestos exposure, as they may come in direct contact with the carcinogenic material in the workplace. Workers in these occupations, as well as their families, are encouraged to participate in periodic mesothelioma screenings. Because the disease may develop years after the individual was exposed to asbestos, it is critical to undergo mesothelioma testing even when no symptoms are obvious.
Mesothelioma Diagnosis
Many mesothelioma cases arise after symptoms occur, and often this is too late. Asbestos-exposed individuals should undergo regular screenings to find potential complications before symptoms occur. Physicians combine different approaches for mesothelioma screenings, including using these imaging techniques:
Radiography: imaging techniques that uses X-rays to project a picture of a certain structure;
Computed Tomography (CT Scan): allows a more detailed view and can be used to show fluid around the lungs and scarring inside the lungs;
Magnetic Resonance Imagining (MRI): used to show the area cancer has invaded and as a tool for staging the cancer;
Ultrasonography: used to show effusions or pleural thickening and may be used as a video-guide if biopsies are necessary; and
In addition, mesothelioma victims often show abnormal concentrations of osteopontin and soluble mesothelin-related peptides (SMRP). By combining mesothelioma blood tests for these molecules and some of the above imaging techniques, physicians are often able to diagnose malignant mesothelioma before severe symptoms appear. If these screening methods are not sufficient, the physician may use invasive methods, such as a thoracoscopy or biopsy.
The Threat of Mesothelioma’s Long Latency Period
One of the major issues with mesothelioma cancer is that it creeps up years after asbestos exposure. Scientists are still researching the disease, but it has been found that gender and exposure time have an effect on the latency period. The time lag presents a threat to those developing the disease: even when clear symptoms show, the victim may not think asbestos long ago was the cause. Because one never knows when the disease will fully develop, the best practice against it is frequent screening to catch any potential complications before they mature.
If the results to your mesothelioma screening are positive for malignant mesothelioma, you may be entitled to financial compensation. Nemeroff Law Firm can fight for your rights. Contact our office at 866-342-1929 or fill in your information on our website for a free case evaluation.
Throughout the years, shipbuilders prided themselves on using the best techniques and materials to send people across the seas. Little did they know that one of the natural materials relied on—asbestos—was toxic. Although shipbuilders stopped using asbestos components in the 1970s, people today who were exposed decades ago are suffering the ill effects of asbestos exposure in shipyards decades ago. If you worked at Naval Base Kodiak and mesothelioma plagues you today, read on to learn how to protect your legal rights.
Naval Base Kodiak has served the U.S. in various forms through the years. From its beginnings as a naval air station to its present-day operations as a U.S. Coast Guard Air Station, the base’s strategic location made it an important point in U.S. military operations on the West Coast. But, while it offered protection for the country’s citizens in times of war or peace, those who worked there suffered asbestos exposure at Naval Air Station Kodiak, leaving a legacy beyond mere memories.
The Establishment of Naval Base Kodiak
Naval Air Station Kodiak was established in 1941, commanded by Commander John Perry. The location was chosen for the surrounding ice-free waters. It served as the principal advance naval base in Alaska and the North Pacific at the beginning of World War II. Ships and submarines from Naval Base Kodiak played a critical role in the Aleutian campaign.
Nearby Fort Greely supplied coast artillery and infantry troops to defend against possible invaders. Fort Abercrombie was established as a sub-post of Fort Greely with a permanent 8-inch gun battery in 1943.
Kodiak Welcomes the U.S. Coast Guard
In 1947, the Coast Guard Air Station joined the naval base as an air detachment at Naval Air Station Kodiak. The U.S. Navy left Kodiak in 1971. The base is now known as Integrated Support Command Kodiak, the largest operating base of the U.S. Coast Guard in Kodiak, Alaska. Integrated Support Command Kodiak is homeport to USCGC Alex Haley, USCGC Storis, and USCGC Spar.
Naval Base Kodiak and Mesothelioma: The Dark History of the Base
Ships and aircraft that passed through Naval Base Kodiak were built using components that contained asbestos. Until the 1970s, asbestos was in common use because of its heat resistance, fire resistance, water resistance, and resistance to corrosion. It was cheap and readily available, so it could be found in wall insulation, floor and ceiling tiles, fire doors, valves, gaskets, boilers, turbines, incinerators, engine rooms, sealants, cement, hot water pipes, steam pipes, welding blankets, and rope.
It was later learned that material was also a health hazard, so asbestos exposure is now part of the base’s legacy. Workers at the base were exposed to asbestos without the benefit of protective clothing or gear.
Asbestosis is a scarring of the lungs brought on by inhaling asbestos fibers. It is characterized by shortness of breath, not coughing, and can lead to respiratory failure. Asbestosis is an irreversible condition that can also lead to an increased risk of developing mesothelioma and lung cancer.
Mesothelioma is an aggressive form of cancer that attacks the mesothelium, the lining that surrounds the lungs. It cannot be diagnosed for 20 to 50 years after initial asbestos exposure because the symptoms take so long to manifest. Symptoms of mesothelioma can mimic other illnesses such as pneumonia and lung cancer, so it is important to naval base workers to inform their doctors of their history of exposure to asbestos in order to obtain an accurate diagnosis.
Mesothelioma has no cure, and it is resistant to traditional cancer treatments like radiation and chemotherapy. After receiving a diagnosis of mesothelioma, many patients only have about one year to live.
The Relationship Between Naval Base Kodiak and Mesothelioma and You
Naval Base Kodiak workers should monitor their health carefully and consult a doctor if they experience any symptoms associated with mesothelioma. People who worked at Naval Base Kodiak and are diagnosed with mesothelioma should also consider contacting a lawyer to discuss their legal rights.
Shipyard Asbestos Exposure: Your Next Steps
If you worked at Naval Base Kodiak and mesothelioma is your diagnosis, you need an experienced mesothelioma attorney to explain your rights and fight for compensation for you. At Nemeroff Law Firm, our team of mesothelioma lawyers has won settlements and verdicts for asbestos nationwide. Call us toll-free at 866-342-1929 or complete our online contact form for a free case evaluation. We’re here to fight for you.
Shipbuilding has a long proud, history of innovation, craftsmanship, and furthering the expansion of the human world. But shipbuilding from the not-so-distant past also leaves another legacy: mesothelioma from asbestos exposure. This is the story of mesothelioma from Bender Shipbuilding and Repair Company.
What you Need to Know About Mesothelioma From Bender Shipbuilding and Repair Company
Bender Shipbuilding and Repair Company began in the early 20th century as a machine shop and blacksmith shop. When it began to specialize in shipbuilding, the company used the materials common of the day. One of those materials was asbestos. Horribly, the exposure to that substance may haunt workers decades later.
The Early Years of Bender Shipbuilding and Repair Company
Bender Welding and Machine Company began as a sole proprietorship in 1919; the company was incorporated in 1923 and moved to a larger facility. While it began as a machine shop and blacksmith shop, in 1952, the company began to focus on building small tugboats and barges as well as top-side and dry dock repairs. The company name, however, did not change to Bender Shipbuilding and Repair Company until 1980. The Bender Welding and Machine Company’s first big job was the construction of Ladd Stadium in 1947.
Bender Shipbuilding in World War II
During World War II, Bender Welding and Machine Company helped construct Liberty ships for the U.S. Navy. The shipyard averaged building one ship every 43 days. Shipyard workers constructed ships for the British fleet even before the United States entered the war.
Bender Shipbuilding Today
The Bender Shipbuilding and Repair Company operates 12 yards with over 7,000 feet of deep water frontage. It also boasts 11 overhead cranes, a 64-ton floating derrick crane, four floating dry docks capable of lifting over 24,000 tons, and over 150,000 square feet of shop and warehouse space.
The Bender shipyard is one of only a few full-fledged shipbuilders in the country, operating around the clock. It is known for new ship construction, repair and conversion, dry dock facilities, and surplus marine equipment sales. Shipyard workers build, service, and repair many types of vessels, including push boats, riverboats, tugboats, shrimp boats, tuna seiners, crabbers, factory trawlers, offshore supply vessels, and passenger vessels. Over 800 Bender-built ships can be found in both private and commercial fleets around the world.
The Danger From Asbestos at Bender Shipyard
Asbestos, a hazardous material known for its fireproofing properties and resistance to corrosion, was commonly used in many shipbuilding components prior to the 1970s, including hot water pipes, steam pipes, boilers, turbines, incinerators, valves, gaskets, between decks and fire doors, and on bulkheads and cabin walls. Shipyard workers suffered asbestos exposure without the benefit of proper respiratory gear or clothing, putting them and their families at risk for contracting serious asbestos-related illnesses.
The risk of asbestos exposure for shipyard workers also extends to their families. Years later, even the families of shipbuilding workers exposed to asbestos at Bender are at risk of developing an asbestos-related disease. Those exposed to asbestos can carry the fibers home on their clothes, skin, and hair. Today, many workers and their families may have developed mesothelioma from Bender Shipbuilding asbestos exposure.
Mesothelioma From Bender Shipbuilding Work: Important Information
Mesothelioma is a fatal form of cancer that attacks the mesothelium in the lungs. Symptoms of mesothelioma do not present until 20 to 50 years after initial asbestos exposure. In fact, when patients are first diagnosed, their symptoms are often mistaken as indicating lung cancer or pneumonia. Doctors often don’t consider a diagnosis of mesothelioma unless they know there is a prior history of asbestos exposure. Once mesothelioma is diagnosed, the prognosis generally gives the patient less than one year to live.
Bender Shipbuilding workers should monitor their health carefully and consult a doctor if they experience any symptoms associated with mesothelioma. Anyone who worked at Bender Shipbuilding in Mobile and is diagnosed with mesothelioma should also consider contacting a lawyer to discuss his or her legal rights.
What to do if You’ve Been Diagnosed With Mesothelioma From Bender Shipbuilding
If you or a loved one has been diagnosed with mesothelioma from Bender Shipbuilding, you need to talk to an experienced mesothelioma attorney. At Nemeroff Law Firm, we have years of experience obtaining settlements and judgments for asbestos victims nationwide to help alleviate the financial burdens caused by this devastating disease. Call us at 866-342-1929 or fill out our online contact form for a free case evaluation. At Nemeroff Law Firm, we fight for you.
Mesothelioma cancer cases are difficult. The people and companies that could have prevented your illness do not want to be held responsible, and they have more financial resources than you do. They dismiss your concerns or low-ball you with a settlement that is to their benefit. Put them on notice that you are up to the fight by choosing an experienced mesothelioma trial attorney, one who will work to hold them accountable and obtain the financial compensation you and your family deserve.
What is a trial lawyer’s strength? Making your opponent dread going to court.
The Advantage of a Mesothelioma Trial Attorney
Assume you have never been to New York City, but find yourself with an urgent reason to go. Driving in NYC is notoriously difficult. You can try it on your own, try to navigate public transportation, or hire a car with an experienced NYC driver. Given the importance of the trip, your best choice is the experienced driver who knows how to avoid congestion and construction and knows the best route to get you to your appointment on time. An attorney experienced in mesothelioma cases is much like that NYC driver.
An experienced mesothelioma trial lawyer knows how to navigate each trial court’s procedures, knows the laws that affect your case, collaborates with others to your benefit, and knows all about cases that are similar to yours.
Look for an outstanding communicator who is comfortable in a courtroom and who is good at persuading attorneys, judges, witnesses, experts, and juries. An experienced trial attorney will be good at “reading the room” and will organize your case in the best way possible within the structure of court rules.
A Good Mesothelioma Trial Attorney Has a Strong Support Team
The best mesothelioma trial attorneys are backed by strong support teams. Their law firms are staffed by trial attorneys with deep experience in asbestos cases and experienced support staff. These firms have access to monetary resources, as well as to experts in the medical, industrial, and science fields. And they also have up-to-date research tools, which allow them to stay current on changes that are critical to your case.
How to Find the Best Mesothelioma Trial Lawyer for You
It’s hard to avoid television commercials asking you to call mesothelioma attorneys about your case. They would like to speak with you. You have some questions to ask them:
How many mesothelioma cases have they taken to trial?
How many mesothelioma cases have they taken to trial in your state?
How many trials resulted in damages being awarded to the plaintiff? What were the damages?
If you are not comfortable with the answer to the last question, find another attorney. Trial attorneys experienced with mesothelioma patients have a passion for getting justice for their clients, who have been wronged by people and corporations who could have prevented their disease from occurring. The relationship between the client (you) and your attorney is crucial.
Our Mesothelioma Trial Attorneys are Passionate About Your Case
The mesothelioma diagnosis that you or your loved one received is devastating. Nemeroff Law Firm has mesothelioma trial attorneys who work nationwide on behalf of victims and their families. We can help you get the compensation you need to pay for the costs of medical treatment and provide support for your family. You are not alone. Contact us today at 866-342-1929, or email us at [email protected]. | 2024-03-03T01:26:28.774034 | https://example.com/article/4956 |
Genetic dissection of Pax6 dosage requirements in the developing mouse eye.
Haploinsufficiency of the transcription factor Pax6/PAX6 has been implicated in a number of congenital eye disorders in humans and mice, such as aniridia and Small-eye, which affect the development and function of the lens, cornea, anterior eye segment and neuroretina. However, the widespread distribution of Pax6/PAX6 protein within the developing and adult eye preclude the identification and direct study of the ocular tissues affected by a reduction in Pax6/PAX6 dosage. Here, we employed Cre/loxP-mediated inactivation of a single Pax6 allele in either the lens/cornea or the distal optic cup to dissect the tissue-specific sensitivity to Pax6 haploinsufficiency. Exclusive inactivation of a single Pax6 allele in the lens recapitulates the Small-eye lens and corneal defects, while only mildly affects iris morphology in a non-cell-autonomous fashion. Conversely, selective inactivation of a single Pax6 allele in the distal optic cup revealed primarily cell-autonomous dosage requirements for proper iris differentiation, with no affects on either lens or corneal morphology. Pax6 dosage within the distal optic cup is found here to influence the number of progenitors destined for the anterior ocular structures, the timing of iris muscle-cell differentiation and iris stroma development. Taken together, we genetically dissected the complex mouse Small-eye phenotype, thereby pinpointing the underlying Pax6/PAX6 haploinsufficiency to autonomous dosage requirements within the developing iris and lens/cornea tissues. | 2023-08-03T01:26:28.774034 | https://example.com/article/5749 |
Q:
"Authorisation is required to perform that action" message, even after clicking "Allow"
I've recently run into an issue authorising a new Google App Script project, specifically one using the Cloud SQL admin API.
The same code exists in previously authorised GAS projects and works fine, but if I take a copy of the GAS project and try to run a function for the first time I'm unable to complete the authorisation process. The screens I'm going through are listed below:
Authorisation Required. - clicked "Review Permissions"
Choose an account to authorise the Google project. - clicked my account
This app isn't verified! - clicked "Go to project
(unsafe)"
Google project wants access to this list of scopes.- clicked "Allow"
Authorisation is required to perform that action.
The warning screen (3) is a recent addition to the process. I don't rememeber encountering it when I've created and run new projects earlier this year. I'm wondering if Google has made any changes to their security implementation of OAuth2.0 recently.
Also, this issue only seems to affect REST calls to the Cloud SQL admin API. In the same project mentioned above I am able to run functions which write data to BigQuery tables in the same Google project which is also hosting the Cloud SQL instances. Clearly some scopes and code can be made to work.
The "https://www.googleapis.com/auth/sqlservice.admin" scope is included in the list of those I requested and approve. I even tried manually editing the URL to add more scopes being requested and it still doesn't get me passed the "Authorisation is required to perform that action" screen.
Does anyone have any idea's?
EDIT:
The code in question which is triggering the authentication.
// Function to get the ip address of a given CloudSQL instance
function _getInstanceIpAddress_(projectId, sqlInstance) {
var token = _getAuthenticationToken_();
// Create the header authorisation
var headers = {
"Authorization": "Bearer " + token
};
// Create the Cloud SQL instances get parameters
var parameters = {
"method": "get",
"headers": headers,
"instance": sqlInstance,
"project": projectId,
"muteHttpExceptions": true
};
// Create the url of the sql instances get API
var api = "https://www.googleapis.com/sql/v1beta4/projects/" + projectId + "/instances/" + sqlInstance + "?fields=ipAddresses";
try {
// Use the url fetch service to issue the https request and capture the response
var response = UrlFetchApp.fetch(api, parameters);
// Extract the ip address of the instance from the response
var content = JSON.parse(response.getContentText());
return content.ipAddresses[0].ipAddress;
} catch(err) {
_log_('ERROR', 'Getting ' + sqlInstance + ' instance ip address failed: ' + err);
return null;
}
}
function _getAuthenticationToken_() {
// Check we have access to the service
var service = getService();
if (!service.hasAccess()) {
var authorizationUrl = service.getAuthorizationUrl();
_log_('INFO', 'Open the following URL and re-run the script: ' + authorizationUrl);
return;
}
Logger.log('Passed Authentication');
//Get the Access Token
return service.getAccessToken();
function getService() {
// Create a new service with the given name. The name will be used when
// persisting the authorized token, so ensure it is unique within the
// scope of the property store.
return OAuth2.createService('companyName-dev-service')
// Set the endpoint URLs, which are the same for all Google services.
.setAuthorizationBaseUrl('https://accounts.google.com/o/oauth2/auth')
.setTokenUrl('https://accounts.google.com/o/oauth2/token')
// Set the client ID and secret, from the Google Developers Console.
.setClientId(CLIENT_ID)
.setClientSecret(CLIENT_SECRET)
// Set the name of the callback function in the script referenced
// above that should be invoked to complete the OAuth flow.
.setCallbackFunction('authCallback')
// Set the property store where authorized tokens should be persisted.
.setPropertyStore(PropertiesService.getUserProperties())
// Set the scopes to request (space-separated for Google services).
// this is admin access for the sqlservice and access to the cloud-platform:
.setScope(
'https://www.googleapis.com/auth/sqlservice.admin ' +
'https://www.googleapis.com/auth/cloud-platform')
//Removed because this Should be covered by cloud-platform
//'https://www.googleapis.com/auth/devstorage.read_write '
// Below are Google-specific OAuth2 parameters.
// Sets the login hint, which will prevent the account chooser screen
// from being shown to users logged in with multiple accounts.
.setParam('login_hint', Session.getActiveUser().getEmail())
// Requests offline access.
.setParam('access_type', 'offline')
// Forces the approval prompt every time. This is useful for testing,
// but not desirable in a production application.
.setParam('approval_prompt', 'force');
}
function authCallback(request) {
var cloudSQLService = getService();
var isAuthorized = cloudSQLService.handleCallback(request);
if (isAuthorized) {
_log_('INFO', 'Access Approved');
return HtmlService.createHtmlOutput('Success! You can close this tab.');
} else {
_log_('INFO', 'Access Denied');
return HtmlService.createHtmlOutput('Denied. You can close this tab');
}
}
}
A:
We had a similar issue with the Google Compute Engine API. Setting the scopes explicitly in the appsscript.json file as per this article solved it for us:
"oauthScopes": [
"https://www.googleapis.com/auth/spreadsheets.readonly",
"https://www.googleapis.com/auth/userinfo.email",
"https://www.googleapis.com/auth/script.container.ui",
"https://www.googleapis.com/auth/script.external_request",
"https://www.googleapis.com/auth/spreadsheets",
"https://www.googleapis.com/auth/compute",
"https://www.googleapis.com/auth/cloud-platform"
],
| 2024-04-12T01:26:28.774034 | https://example.com/article/5930 |
Growth curves and the international standard: How children's growth reflects challenging conditions in rural Timor-Leste.
Population-specific growth references are important in understanding local growth variation, especially in developing countries where child growth is poor and the need for effective health interventions is high. In this article, we use mixed longitudinal data to calculate the first growth curves for rural East Timorese children to identify where, during development, deviation from the international standards occurs. Over an eight-year period, 1,245 children from two ecologically distinct rural areas of Timor-Leste were measured a total of 4,904 times. We compared growth to the World Health Organization (WHO) standards using z-scores, and modeled height and weight velocity using the SuperImposition by Translation And Rotation (SITAR) method. Using the Generalized Additive Model for Location, Scale and Shape (GAMLSS) method, we created the first growth curves for rural Timorese children for height, weight and body mass index (BMI). Relative to the WHO standards, children show early-life growth faltering, and stunting throughout childhood and adolescence. The median height and weight for this population tracks below the WHO fifth centile. Males have poorer growth than females in both z-BMI (p = .001) and z-height-for-age (p = .018) and, unlike females, continue to grow into adulthood. This is the most comprehensive investigation to date of rural Timorese children's growth, and the growth curves created may potentially be used to identify future secular trends in growth as the country develops. We show significant deviation from the international standard that becomes most pronounced at adolescence, similar to the growth of other Asian populations. Males and females show different growth responses to challenging conditions in this population. | 2023-12-30T01:26:28.774034 | https://example.com/article/6706 |
/*
Copyright The Guard Authors.
Licensed under the Apache License, Version 2.0 (the "License");
you may not use this file except in compliance with the License.
You may obtain a copy of the License at
http://www.apache.org/licenses/LICENSE-2.0
Unless required by applicable law or agreed to in writing, software
distributed under the License is distributed on an "AS IS" BASIS,
WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
See the License for the specific language governing permissions and
limitations under the License.
*/
| 2024-01-20T01:26:28.774034 | https://example.com/article/9171 |
このサイトで使用されている写真および文章を無断で使用することはできません
The photograph and sentences used on this site cannot be used without permission.
Copyright © New Japan Pro-Wrestling Co,.Ltd. All right reserved. | 2024-01-24T01:26:28.774034 | https://example.com/article/1543 |
Omentum and basic fibroblast growth factor in healing of chronic gastric ulcerations in rats.
Omentum was shown to exhibit angiogenic activity, but its role in healing of chronic gastric ulcers is unknown. This study was designed to compare the effects of omentum and basic fibroblast growth factor (bFGF), a potent angiogenic factor, on healing of chronic gastric ulcers in rats. Several series of rats with gastric ulcers were used: series A with intact omentum (control), series B with omentum resected, and series C with omentum placed on the serosal side of the ulcer. Series A-C were divided into four groups treated with vehicle (I); indomethacin (II), an inhibitor of prostaglandin formation, difluoromethylornithine (DFMO) (III); an inhibitor of polyamine biosynthesis or bFGF (IV). Seven days after ulcer induction, the animals were anesthetized, the gastric blood flow (GBF) was determined by laser Doppler flowmetry (LDF), and the ulcer area was measured by planimetry. Biopsy samples of the ulcer margin were taken for determination of the number of capillaries and myofibroblasts in the granulation tissue. Attachment of omentum significantly accelerated ulcer healing, whereas omentectomy delayed this process. LDF revealed the decrease in the GBF at the ulcer margin to 45% and at the ulcer bed to 18% of the value recorded in the intact adjacent mucosa. Attachment of the omentum significantly increased the blood flow at the ulcer margin and increased the number of capillaries and myofibroblasts in the granulation tissue. Indomethacin (1 mg/kg/day) that inhibited mucosal PGE2 by about 85% delayed significantly ulcer healing without affecting the blood flow in the ulcer area.(ABSTRACT TRUNCATED AT 250 WORDS) | 2023-11-30T01:26:28.774034 | https://example.com/article/2009 |
Q:
Solvable group of certain order
We know that in a non-abelian group of order $p^2q$ ($p$ and $q$ are distinct primes),
if $p>q$ and it's Sylow $p$-subgroup is elementary abelian $p$-group, then one of the presentations for $G$
is $$\langle a , b ,c \mid a^p=b^p=c^q=1, ab=ba, cac^{-1}=a^{i}b^{j}, cbc^{-1}=a^{k}b^{l}\rangle,
$$
where
$$
\begin{pmatrix}
i & j\\
k & l
\end{pmatrix}
$$has order $q$ in $\operatorname{GL}(2,p)$.
(According to Burnside's classification in his book "Theory of groups of finite order").
Is it true that this group has NO subgroup of order $pq$?
A:
Might well have one. Consider the case where $p$ is any odd prime, $q = 2$, and
$$\begin{pmatrix}
i & j \\
k & l
\end{pmatrix}
=
\begin{pmatrix}
-1 & 0 \\
0 & -1
\end{pmatrix}.
$$
Here any $\langle a^{u} b^{v}, c \rangle$ has order $pq$, for $a^{u} b^{v} \ne 1$.
In general, if
$$M = \begin{pmatrix}
i & j \\
k & l
\end{pmatrix}$$
has eigenvalues in $\mathbb{F}_{p}$, there is at least one subgroup of order $p q$, generated by $c$ and an eigenvector. (Actually, there are at least two such subgroups, see below.) Conversely, let $H$ be a subgroup of order $pq$, then clearly $H \cap \langle a, b \rangle$ has order $p$, and it is a normal subgroup of $H$, so if $H \cap \langle a, b \rangle = \langle a^{u} b^{v} \rangle$, then
$$
c (a^{u} b^{v}) c^{-1}= (a^{u} b^{v})^{\lambda}
$$
for some $\lambda \ne 0$, so the vector $(u, v)^{t}$ is an eigenvector with respect to the eigenvalue $\lambda \in \mathbb{F}_{p}$.
Now for $M$ to have eigenvalues in $\mathbb{F}_{p}$, you need $q$ to divide $p-1$. First note that if $M$ has only the eigenvalue $1$, then $M^{p} = I$, against the assumptions. If $\lambda \in \mathbb{F}_{p}^{\star}$ is an eigenvalue of $M$, it satisfies both $\lambda^{q} = 1$ and $\lambda^{p-1} = 1$. If $\lambda \ne 1$, we have $\gcd(q, p-1) \ne 1$, and thus $q \mid p - 1$.
So if $q \nmid p-1$, there is no subgroup of order $pq$. If $q \mid p-1$, then $M^{p-1} = I$, the identity, so the minimal polynomial of $M$ divides $x^{p-1} - 1$, which has $p-1$ distinct roots in $\mathbb{F}_{p}$, so that $M$ is diagonalisable. It follows that
there is a subgroup of order $pq$ in $G$ iff $q \mid p - 1$.
| 2024-06-17T01:26:28.774034 | https://example.com/article/4873 |
[](https://github.com/fluttercandies/ncov_2019/stargazers)
[](https://github.com/fluttercandies/ncov_2019/network)
[](https://github.com/fluttercandies/ncov_2019/issues)
> 如果产生其他依赖无法编译的问题，可以尝试将`pubspec.yaml`中的`dependencies`中的所有依赖的"^"去掉，重新编译尝试。
# nCoV_2019
获取新肺炎实时动态App，支持Android和IOS。
# Log
* 2020.07.04 - 适配Flutter 1.17
* 2020.02.16 - 修复统计图不能展示问题。（16:45）
* 2020.02.16 - 辟谣卡片标题最大行数调整为2行，统计数据布局优化。（16:32）
* 2020.02.16 - 完美适配Flutter1.12.13和Androidx（13:21）
* 2020.02.06 - 修复了统计信息出错和诊疗无图标和对齐问题。
* 2020.02.02 - 修复了统计的分隔符导致统计数据无法正常显示。
# 项目相关文章
* [Flutter Candies又添一成员，为抗击疫情贡献一份技术力量](https://mp.weixin.qq.com/s?__biz=MzAxMTI4MTkwNQ==&mid=2650829796&idx=1&sn=7811875471dcabd0cfec788adc27306a&chksm=80b7a77ab7c02e6cfc9726c61be31cbd616c5593d0b9388776f15fd255ccc619be7df38341b3&mpshare=1&scene=23&srcid&sharer_sharetime=1582430519570&sharer_shareid=bdfd1967c1c7dae7e61a030ea5b2b235%23rd)
# App体验
##### Android 下载地址:
[http://www.flutterj.com/nCoV-2019.apk](http://www.flutterj.com/nCoV-2019.apk)
##### Android（二维码下载）:
IOS:
拉下代码直接跑即可
# App效果图
||  |  |  |
| --- | --- | --- | --- |
||  |  |  |
# 使用须知
* cached_network_image
在`pubspec.yaml`文件中，关于flutter版本使用`cached_network_image`插件问题，默认使用2.0.0，
因为你们刚安装上flutter为最新版本flutter。
```yaml
# cached_network_image: 1.1.1 # 1.9.0左右flutter版本的用这个
cached_network_image: 2.0.0 # 2.0.0左右flutter版本直接用这个
```
# 使用教程
* 使用命令（拉取项目）：$ git clone https://github.com/fluttercandies/ncov_2019.git
* 然后命令（获取依赖）：$ flutter packages get (IOS执行IOS部分再执行下一步)
* 最后命令（运行）：$ flutter run
IOS
* 进入项目IOS目录：$ cd ios/
* 更新Pod（非必须）：$ pod update
* 安装Pod：$ pod install
# 我的Flutter环境
```
q1deMacBook-Pro:ncov_2019 q1$ flutter doctor -v
[✓] Flutter (Channel stable, 1.20.2, on Mac OS X 10.14.5 18F2059, locale zh-Hans-CN)
• Flutter version 1.20.2 at /Users/q1/flutter
• Framework revision bbfbf1770c (3 weeks ago), 2020-08-13 08:33:09 -0700
• Engine revision 9d5b21729f
• Dart version 2.9.1
• Pub download mirror https://pub.flutter-io.cn
• Flutter download mirror https://storage.flutter-io.cn
[✓] Android toolchain - develop for Android devices (Android SDK version 29.0.3)
• Android SDK at /Users/q1/Library/Android/sdk
• Platform android-29, build-tools 29.0.3
• ANDROID_HOME = /Users/q1/Library/Android/sdk
• Java binary at: /Applications/Android Studio.app/Contents/jre/jdk/Contents/Home/bin/java
• Java version OpenJDK Runtime Environment (build 1.8.0_242-release-1644-b3-6222593)
• All Android licenses accepted.
[✓] Xcode - develop for iOS and macOS (Xcode 11.3)
• Xcode at /Applications/Xcode.app/Contents/Developer
• Xcode 11.3, Build version 11C29
• CocoaPods version 1.8.4
[✓] Android Studio (version 4.0)
• Android Studio at /Applications/Android Studio.app/Contents
• Flutter plugin version 48.1.2
• Dart plugin version 193.7361
• Java version OpenJDK Runtime Environment (build 1.8.0_242-release-1644-b3-6222593)
[✓] VS Code (version 1.47.3)
• VS Code at /Applications/Visual Studio Code.app/Contents
• Flutter extension version 3.12.2
[✓] Connected device (1 available)
• sdk gphone x86 arm (mobile) • emulator-5554 • android-x86 • Android 11 (API 30) (emulator)
• No issues found!
```
# 意见反馈
如果大家有好的意见或者有好的设计图的话可以群内找我。
Flutter交流QQ群：[874592746](https://jq.qq.com/?_wv=1027&k=5coTYqE)
Flutter交流微信群：
<img src="assets/git/left_group.png" height="200" width="210" style="zoom:30%;" />
[上图无法显示点我](http://www.flutterj.com/left_group.png)
### LICENSE
```
fluttercandies/ncov_2019 is licensed under the
Apache License 2.0
A permissive license whose main conditions require preservation of copyright and license notices.
Contributors provide an express grant of patent rights.
Licensed works, modifications, and larger works may be distributed under different terms and without source code.
```
| 2023-09-20T01:26:28.774034 | https://example.com/article/8148 |
Q:
How do you vertically center legends using Google Charts API?
I'm having trouble vertically centering the legends in Google Charts Pie Graph. Anyone have previously experience? Or is the best bet to code my own pie graph?
Thanks in advance,
Walker
A:
Use the following in the charts option:
var options = {
title: 'My Daily Activities',
legend: {'position':'top','alignment':'center'},
};
The "legend.alignment" can be found in this documentation:
https://developers.google.com/chart/interactive/docs/gallery/piechart?csw=1
| 2024-07-23T01:26:28.774034 | https://example.com/article/4646 |
OCTOBER 16, 1961
NEW YORK—I have been receiving an increasing number of letters from groups who want to have
peace demonstrations of one kind or another.
The latest one came from a young girl in San Francisco who attended a meeting at Hyde
Park last summer. At that time she asked me about peace and how young people could
keep from "being afraid." I gave her a general answer, saying that we must first develop
the capacity to live peacefully with ourselves, and then to feel at peace with our
surroundings, our family and our friends. Once this is achieved, we may then be able
to be of use in trying to bring about a peaceful atmosphere between the countries
of the world. She now writes me that students in the San Francisco and Bay area held
a demonstration on October 14 to promote peace, but she would like to feel that they
could make some constructive suggestions of how active citizens could work for peace
and the avenues through which they could do so.
The answer, I think, is that our obligation as citizens is to find out from our own
government what are the helpful things we can do to assist in making the peoples of
the world realize that we as a nation want peace, that we believe in a peaceful world
and are willing to make sacrifices to obtain it. Our great difficulty is that the
maintenance of peace seems to lie in the hands of two nations, the Soviet Union and
ourselves. The Russian leader, Premier Khrushchev, by his many provocative speeches
has made it appear that it is our attitude which is the aggressive one. But when you
study his own proposals you find that while he says he wants peace, he wants it only
on his own terms. Unless we agree to what he wants—to the kind of treaty or the kind
of action on any subject which he wishes to interpret in his own way—then there can
be no agreement between us and he threatens us with annihilation.
Thus, we have had months and months of negotiations on the question of stopping nuclear
tests. In the end, Khrushchev has started nuclear tests in the atmosphere without
regard to what anyone in the world might feel or think about it. He believes that
we were as unreasonable in our demands as we think he was; and neither of us feels
that they can endanger the safety of their people by giving up in any way. As a result,
we in the U.S. find ourselves engaged in rearmament—after having disarmed at the end of World War
II. We look upon every move in space made by the Soviet Union as a danger, and not
as something that might be used by cooperative effort in the U.N. for the benefit of all nations.
Now we find ourselves faced with the dilemma of making Khrushchev understand that
beyond a certain point we cannot yield in any area of the world. We are not interested
in appeasing or giving in to him. But we are very much interested in negotiating with
him, for there are broad areas in which, if he is willing to give a little, we could
also give. Instead of this, we find ourselves obliged to prepare for defense because
we believe he might use an atomic weapon against us. We think he is bluffing and that
he will give in, but we cannot be sure.
The President naturally feels he cannot risk the lives of the people without taking
every known precaution to save as many as possible in case of attack. This is what
leads to a civilian defense program and the request for building shelters. One's private
opinion may be opposed to such measures, but it is understandable that the President
should feel he must prepare for all eventualities. As I have previously said, I think
it should be a thoroughgoing plan made and supervised by the Pentagon. I think we
have the right to ask for this type of shelter program if the President feels the
need of proving that we are willing to do whatever our government asks.
Any demonstration for peace should clearly be an effort to show the world our desire
to support peace, but should not indicate any weakening in the support of our President
in whatever he may think necessary to ask us to do under the present circumstances.
If he does not receive this support, and if Premier Khrushchev is not aware of such
support, it might weaken the President's hand for negotiation. We are, one might say,
in something of a gigantic poker game for the highest stakes that nations have ever
played. | 2024-06-07T01:26:28.774034 | https://example.com/article/4639 |
Wilton Witch Fingers Pretzel Mold
Let's point out a great Halloween treat! With this pretzel mold and easy-melting Candy Melts candy, it's easy to add a great-tasting and colorful candy design to your favorite store-bought pretzels. Easy to use | 2024-06-09T01:26:28.774034 | https://example.com/article/5758 |
Friday, September 25, 2009
Well I'm in NYC
My family drove me and my bike into the city. Took longer than I had hoped, but the kids were troopers. Walked over to Central Park Zoo and looked around a bit.
The kids liked the polar bears and the seals in particular. But they couldn't stay long and just as soon as we got into the City they had to head home.
I am staying at a place called "The Pod". Not surprisingly the rooms are small. Enough room for me my bags and bike. After the family headed out I rode through Midtown to Central Park to check-in and drop off my bike. It was certainly an intersting experience riding that one mile on my own. Tomorrow morning we ride five through town to catch a ferry, but that will be with a group. And that will be a whole new experience for me as well. For now though I just need to rest up.
Climate Ride Links
About Me
I am a professor of physical chemistry at Rider University.
I have a beautiful wife and two really great kids.
I have a number of interests, but little free time to properly pursue them (see items above). | 2024-05-19T01:26:28.774034 | https://example.com/article/7760 |
Analysis of miRNA expression patterns in human and mouse hepatocellular carcinoma cells.
Hepatocellular carcinoma (HCC), one of the most common malignancies in adults displays aberrant miRNA expression during its pathogenesis. We assessed expression of miRNA in surgically resected human HCC of an early stage and murine HCC with a high malignancy in order to find miRNA overexpressed in HCC regardless of tumor stage and underlying etiology. Further, the role of the deregulated miRNA in HCC pathogenesis was investigated. miRNA were isolated from HCC tissues and surrounding non-tumorous tissues from HCC patients and a murine transgenic model of HCC. A quantitative reverse transcription polymerase chain reaction was performed to determine expression levels of miRNA. Human HCC cell lines stably expressing individual miRNA were generated to investigate the biological function of overexpressed miRNA. We found that levels of miR-221, -181b-1, -155-5p, -25 and -17-5p were significantly upregulated in both human and murine HCC regardless of tumor stage, underlying etiology or the presence of fibrosis. Using HCC cell lines stably expressing respective miRNA, we found that miR-221 increased the proliferation of hepatoma cells, while miR-17-5p induced cell migration. We identified miRNA that are consistently upregulated in HCC. The overexpressed miRNA could potentially be used as a bona fide biomarker for HCC. | 2023-08-23T01:26:28.774034 | https://example.com/article/4371 |
Press Release
27
Aug 14
Online sales for CLT20 2014 begins
Tickets for Raipur matches, semis and final will be available soon
Tickets for the Group Stage matches of the Champions League Twenty20 2014, to be played at Mohali, Bengaluru and Hyderabad, are available on www.clt20.com.
The minimum price of the tickets is `100.
The CLT20 2014 will be played from 13 September 2014 to 4 October 2014, at Raipur, Mohali, Hyderabad and Bengaluru.
The tournament will follow a format similar to the three previous editions, with a Group Stage preceded by a Qualifier.
A total of 29 matches will be played in the competition, on 19 match-days. There will be ten double-headers, the semi-finals included.
Hyderabad will host five Group matches, including one double-header. The city will also host the semi-finals on 2 October, which will be a double-header. Bengaluru will host six matches, including two double-headers. The city will also host the final on 4 October 2014. Mohali will host seven Group matches, including three double-headers.
Raipur will host eight matches. These will comprise two Group Stage games, plus all six Qualifier matches. The Qualifier matches will be double-headers.
The online sale of tickets for the Qualifier and Group Stage matches at Raipur, and the box-office ticket sales for all the Qualifier and Group Stage matches, as well as the CLT20 2014 semi-finals and final, will start soon.
Open Questions
Who is the better T20 bowler?
Pulse connects you to the live action
Get closer to CLT20 this season by using Pulse while you watch the LIVE matches. Pulse asks you a range of questions relevant to the LIVE action as it unfolds. Your votes will be featured in the telecast in real-time and debated by the commentators, players and stars. | 2023-11-23T01:26:28.774034 | https://example.com/article/4619 |
22 B.R. 641 (1982)
In re Bennie Lee ASKEW, Debtor.
Patricia Simpson BRAWNER, Plaintiff,
v.
Bennie Lee ASKEW, Defendant.
Bankruptcy No. 82-40109-COL, Adversary Proceeding No. 82-4090-COL.
United States Bankruptcy Court, M.D. Georgia.
August 19, 1982.
Jerry D. Sanders, Columbus, Ga., for plaintiff.
Walter F. Johnson, Columbus, Ga., for defendant.
COMPLAINT TO DETERMINE DISCHARGEABILITY OF DEBT
FINDINGS OF FACT AND CONCLUSIONS OF LAW
ALGIE M. MOSELEY, Jr., Bankruptcy Judge.
Plaintiff seeks nondischargeability of her judgment debt obtained in the Superior Court of Muscogee County, Georgia against defendant, Bennie Lee Askew. This was a joint case in the Bankruptcy Court, but the judgment in the Superior Court was only against the Defendant, and Debtor, Colette Hammond Askew, is not a Defendant in this adversary proceeding. Plaintiff alleges that this judgment was for willful and malicious injury and is nondischargeable under 11 U.S.C. § 523(a)(6) of the Bankruptcy Code. Plaintiff and Defendant have each filed a Motion for Summary Judgment. Herein, Plaintiff's Motion for Summary Judgment is granted.
Plaintiff obtained judgment against Defendant in June, 1975 in the Superior Court of Muscogee County, Georgia for comprehensive damages in the amount of $125,000 and for punitive damages in the amount of $50,000. This judgment followed a jury verdict exonerating a joint defendant, James E. Warren, Jr., and awarded comprehensive damages of $125,000 and punitive damages of $50,000 in favor of the Plaintiff against the Defendant.
The complaint in the Superior Court of Muscogee County, Georgia alleges that the Plaintiff was thirteen years of age, walking five feet off the shoulder of Forrest Road, *642 Defendant at a speed estimated to be from 70 to 100 miles per hour, veered off the road and struck Plaintiff knocking her 50 feet South face down into a ditch, that after striking Plaintiff, Defendant left the scene at a high rate of speed, that at the time Defendant was under the influence of alcohol, that part of Plaintiff's hair was left in the windshield wipers of Defendant's automobile, that the Defendant was driving without a valid Georgia Driver's License, and his driver's license had been suspended as a result of previous driving under the influence records, Defendant was convicted of driving under the influence charges in October of 1970, was charged with driving under the influence in September of 1971 and paid a fine, having eleven days earlier forfeited a bond on public drunkenness charges, in July, 1972, Defendant was charged with driving under the influence and fined, twice in 1973 Defendant was charged with driving under the influence, that his license was suspended on March 12, 1972 and was sentenced to attend the Alcohol Safety Action Project Traffic Information Program, that on May 7, 1974 he forfeited a bond on the charge of public drunkenness, that as a result of being off the highway and striking Plaintiff, Plaintiff was hospitalized and in intensive care, totally unconscious for 36 days, that Plaintiff received severe brain concussion, fractures to both legs and multiple cuts and bruises over Plaintiff's entire body. The complaint in the Superior Court asserts that Defendant negligently injured and damaged Plaintiff and prayed for damages in the amount of $200,000. The complaint was amended, praying for punitive damages in the amount of $100,000.
Although this Court suggested in a letter of May 25, 1982 to counsel for the respective parties that "all or portions of the Superior Court record should be made a part of the record in the instant file," the only items from the record of the Superior Court of Muscogee County, Georgia that are a part of the record in the instant adversary proceeding are the complaint and the judgment, the latter quoting the jury verdict.
Defendant contends that in the exception from discharge in 11 U.S.C. § 523(a)(6) "for willful and malicious injury by the debtor to another entity or to the property of another entity," that "willful" means deliberate and intentional. If deliberate and intentional means that the Defendant must have formulated in his mind an intent to veer off the highway and strike Plaintiff, and having so formulated such intent, he deliberately took aim at her and drove his automobile into her after having taken aim, then this construction is rejected. Whether a person does something deliberately and intentionally can only be determined by his conduct. The conduct in the instant case shows a deliberate and intentional injury to the Plaintiff.
For Defendant's construction of the word willful, Defendant relies upon a statement from legislative history as follows:
"Paragraph (6) excepts debts for willful and malicious injury by the debtor to another person or to the property of another person. Under this paragraph, `willful' means deliberate or intentional. To the extent that Tinker v. Colwell, 139 U.S. 473 [24 S.Ct. 505, 48 L.Ed. 754] (1902) [sic], held that a looser standard is intended, and to the extent that other cases have relied on Tinker to apply a `reckless disregard' standard, they are overruled." H.R.Rep. 595, 95th Cong., 1st Sess. 365 (1977); S.Rep.No.989, 95th Cong., 2nd Sess. 79 (1978), U.S.Code Cong. & Admin.News 1978, pp. 5787, 5865, 6320.
This Court addressed this issue In re Rines, 18 B.R. 666, 8 BCD 1205 (Bkrtcy.M.D.Ga. 1982), and found that these few sentences in the legislative history were insufficient authority for this Court to change long standing opinions from the United States Supreme Court and from a Court of Appeals for the Fifth Circuit. Congress by legislation may change the law as found by the courts, but a few obscure words in the legislative history is insufficient to change the meaning of words interpreted by the courts. See In re Rines, supra, and the cases cited there. In re Rines was affirmed *643 by the District Court on appeal without opinion.
To In re Rines we might add the following: In In re Vickers, 546 F.2d 1149, 1150 (1977), the Fifth Circuit Court of Appeals said in interpreting the same words, willful and malicious, under the Bankruptcy Act,
"The standard interpretation of this intent [of willfulness and malice] requirement, applied by the referee below, is as follows:
In order that a provable liability come within this exception the injuries must have been both willful and malicious. An injury to person or property may be a malicious injury within this provision if it was wrongful and without just cause or excuse, even in the absence of personal hatred, spite or ill will. The word "willful" means nothing more than intentionally doing an act which necessarily leads to injury. Therefore, a wrongful act done intentionally, which necessarily produces harm and is without just cause or excuse, may constitute a willful and malicious injury.
1A Collier on Bankruptcy ¶ 17.17, pp. XXXX-X-XXXX.6 (1976)."
Also, the Court of Appeals for the Fifth Circuit in In re Dardar, 620 F.2d 39, 40 (1980), said
"[2] Collier's interpretation of the phrase `willful and malicious' was adopted by the Fifth Circuit in Vickers v. Home Indemnity Co., 546 F.2d 1149 (5th Cir. 1977). Thus, an injury to a person is nondischargeable as a malicious injury if
the injury [is] both willful and malicious. Willful means nothing more than intentional, and malice is not limited to personal hatred, spite, or ill will. Therefore, a wrongful act done intentionally, which necessarily produces harm is without just cause or excuse, may constitute a willful and malicious injury.
1 Collier, Bankruptcy ¶ 17.03 (1978) (footnotes omitted)."
The ultimate question in this case is whether or not the sentences from the legislative history cited above is sufficient authority for this Court to change the meaning of willful and malicious as found by the Court of Appeals of the Fifth Circuit and the Supreme Court in Tinker v. Colwell, 193 U.S. 473, 24 S.Ct. 505, 48 L.Ed. 754 (1904). This Court will adhere to its decision in In re Rines and conclude that it is not. The comments relied upon by Defendant are comments of the House Judiciary and the Senate Judiciary Committees. These comments were not adopted or approved by the full Congress. The language used in the Code, which was approved by the full Congress, had been held, in Tinker and other cases under the Act, to have a meaning. This meaning is the meaning ascribed by this Court. Congress must have been aware of this meaning. If the full Congress had intended to change this meaning, it would have changed the words. It did not. Therefore, the words should be construed to have the same meaning as under the Act. See Lorillard v. Pons, 434 U.S. 575, 98 S.Ct. 866, 870, 55 L.Ed.2d 40 (1978); Shapiro v. U.S., 335 U.S. 1, 68 S.Ct. 1375, 1383, 92 L.Ed. 1787 (1948); U.S. v. Falletta, 523 F.2d 1198, 1201 (5th Cir. 1975) reh. den. 525 F.2d 1407. Further, the meaning of the quoted portion of the legislative history raises more questions than it purportedly answers. It is at best unclear and ambiguous. See cases cited in In re Rines, supra.
The instant case is factually similar to In re Willis, 2 B.R. 566 (Bkrtcy.1980) from this Court, and that case will also be adhered to. The Defendant is collaterally estopped from relitigating in the Bankruptcy Court those questions actually and necessarily decided in the prior suit in the Superior Court of Muscogee County. The Superior Court of Muscogee County, Georgia "actually and necessarily decided" that the debt of Defendant to Plaintiff was a liability for willful and malicious injuries to the person of the Plaintiff, and, accordingly, the Motion for Summary Judgment filed by the Plaintiff should be granted, and the Motion for Summary Judgment filed by the Defendant should be denied.
| 2024-05-14T01:26:28.774034 | https://example.com/article/8107 |
Q:
Codeigniter 2.0 third_party folder
What is this the third_party folder in codeigniter 2.0 and how to use that?
A:
Packages are new to CI2.0 that allow for the easy distribution of complete sets of resources in a single directory, containing models, libraries, helpers etc...but not to be confused with modules, as Phil Sturgeon points out quite helpfully.
$this->load->add_package_path()
See the docs for more
A:
If your "third party library code" requires a single file to be "loaded" in order for you to make full use of the library then it should go in your libraries directory. If your "third party library code" is a folder full of files, many of which may be "loaded" and made use of, then it should go in your third_party directory.
That's my interpretation of the CodeIgniter docs for the Loader Class found here: https://www.codeigniter.com/user_guide/libraries/loader.html
Is my interpretation incorrect? If so LMK!
| 2024-01-22T01:26:28.774034 | https://example.com/article/4010 |
Q:
Hibernate: Collection does not repopulate after save of Many-to-Many join
I just need to figure out why my collection of Roles would not populate member properties after save (add). I have two tables, User and Role, and the join table UserRole.
public class User implements Serializable {
private int id;
@NotBlank(message = "{User.userName.notBlank}")
@AlphaNumeric(message = "{User.userName.alphaNumeric}")
private String name;
@NotBlank(message = "{User.password.notBlank}")
@AlphaNumeric(message = "{User.password.alphaNumeric}")
private String password;
private boolean enabled;
private boolean deleteSafe;
@NotEmpty(message="{User.roles.notEmpty}")
private Set<Role> roles; <-- this is my problem
And here is my Hibernate XML mapping
<class name="User">
<id name="id">
<generator class="identity" />
</id>
<property name="name"></property>
<property name="password"></property>
<set name="roles" table="UserRoles" lazy="false">
<key column="userId"></key>
<many-to-many column="roleId" class="Role"></many-to-many>
</set>
</class>
And here is the simple Role class
public class Role implements Serializable {
private int id;
private String authority;
private String name;
My UserRole table consists only of two columns, userId which maps to the id of User, and roleId, which maps to the id in Role.
I pass a User object with name, password, and a set of Roles. Each Role in this list only has the id populated. The UserRole table gets saved properly, but I want that after saving, the Set in my User object will have the authority and name attributes populated.
Those properties are populated in a normal 'get' User using the same mapping, I was hoping it will do the same after it does a 'save'.
A:
hibernate won't do that. You basicly have a broken model here and hibernate can not distinguish between a Role with password set to null and a dummy Role which you want it to populate. If you just want to assign Roles with known ids to the newly created User then use session.load().
for(long roleId : roleIds)
{
newUser.getRoles().add(session.load(Role.class, roleId));
}
the Roles returned by session.Load are proxies which do not generate a roundtrip until they are accessed.
Update: if you know you need the roles later then eager loading them would be better
for(Role role : session.CreateCriteria(Role.class).add(Expression.in("id", roleIds)).list())
{
newUser.getRoles().add(role);
}
| 2023-11-16T01:26:28.774034 | https://example.com/article/1600 |
Thursday, March 30, 2006
What can the government do about Road Deaths?
A mate told me this story. He was driving down a twisty turny mountainous road. In front of him was 2 cars and behind was a van. The van then decided to overtake all three cars. So the van driver put the foot down and accelerated passing out the three cars and cutting right across a blind corner to get back on correct side of the road. 10 seconds later and female driver came up on the other side of the road. If that female driver had left her house 10 seconds earlier she would have come around the corner and hit the van. She would not have seen it coming and probably would have died. Also the other three cars would probably have been in a pile up and more lives could have been lost. Maybe before leaving the woman might have changed the radio station taking 10 seconds, maybe she had trouble closing her house door lasting 10 seconds what ever delayed her that 10 seconds saved her life. From all the times you have been driving how often have you been 10 seconds from death. Road deaths are a national emergency. Since January 1 roughly 89 people have died on our roads, that is pretty much over one a day. But the government are not really to blame for road deaths.
Many people blame the road network and like to use the statistic that the fast roads in the country are the safest. This is a nonsense argument. The main cause of road fatalities and what the government have to deal with is not anything tangible like road quality it is to do with people not taking responsibility for there own actions.
Many road in Ireland are of poor quality and people know this. So they should act accordingly if a road is a twisty turny road don’t speed and don’t over take on a blind bend. All these things make sense to most people but why do people not take responsibility for their own actions. Instead with everything that goes wrong in this country instead of taking responsibility as we would have in yester year we blame the government and expect them act like parents mollycoddling us as if we are irresponsible kids that know no better.
Another argument is that we need more enforcement of the law. Basically what we are asking the government to stop people being stupid and irresponsible. Would we inspect the Gardai to force people not to put their ATM pin number in the newspapers. No of course not because no one would be that irresponsible. But for some reason when dealing with road deaths we never deal with the irresponsibility.
The reason of course is that the person who acts irresponsibly, does not just get their bank account emptied they hit someone in a car that is acting responsibly. Thus the government has to introduce measures to combat stupidity. We Irish are the most informed about the number of road deaths in Europe yet we don’t seem to get the fact that we need to cop on. So what needs to be done.
A Garda traffic corp needs to be put in place the only thing that will slow down people is enforcement of the speed limits. We also need speed cameras. Anyone that says the speed cameras are just a money making device. I say if you do not break the speed limit you do not get fined. Also if you wish to make the argument that you can get done 5 km over the limit. Remember the speed limit is a limit not a suggestion.
Penalty point should also be enforced it is no use having laws if they are not enforced. When they were introduced back in 2002 they did work and reduce fatalities but it was not enforced and people being people were irresponsible and thought sure it is only against the law if I am caught. Hands up who has not driven while using a mobile phone without hands free.
Another option to bring in is to limit engine size or put speed limiters for drivers of a certain age. This is an ok measure but will do little. In the above anecdote the speed wasn’t the problem it was the fact the driver did a horrendously dangerous manoeuvre whether that is carried out at 120kmph or 100kmph would not change the fact that a live would be lost.
Teenagers in schools do not receive education in road safety. The point of education is to educate for living in a society. Schools need to start giving driving lessons as part of the school curriculum. Also the driving test needs to be changed. There is something fundamentally wrong when someone fails their driving test thus judged not competent enough to drive on the road and then drive home.
Drink driving is still rampant, publicans especially rural ones who are on first name terms with many of their customers and who know well who is driving still will fire out rakes of pints. Guinness Mid strength may come the drink of choice of people who are the designated driver. While 1 pint of it will keep you under the limit 10 pints of it wouldn’t. Also the limit is not a target it is the maximum. No alcohol should be consumed at all. An EU survey has placed Ireland at the bottom of the Euro-league for improving road safety. We need to seriously work on this. We need to enforce the law more, straighten roads even place restrictions on car engines
This may well be an issue in the next election. Even though it seems wrong that we have to legislate simple cop on but hey that is the world we live in.
2 comments:
Good blog. Its about time people realised that road safety like safety in the home is our responisbility. Yes you can't be blamed for other drivers stupidity but you can ensure that you drive with as much care as required. In your example maybe nothing delayed the lady the 10 seconds at home maybe she new that bend was coming and so slowed down even further which caused he geting their 10 seconds later.
People just don't give a feck. Everybody thinks there Mick Schumacher when they get behind the wheel of a car. They hear of accidents, but think the same rules don't apply to them. They either don't see any danger or just don't care.
I see it every morning on my commute to college along twisty country roads. People passing me at around 80-90 MPH and i keep thinking to myself 'just get up 5 minutes earlier, you freaking Jackass!'. | 2024-01-05T01:26:28.774034 | https://example.com/article/3309 |
Now for the good news, He wants to set in with the ya'll when you meet with
Mary. I'd just have the meeting then tell him about it. He also wants them
off the place in 14 days. I told him no, to chill and that we will buy him
out. That should hold him off a few days. So don't move yet on getting my
money together?
Took Barb out to eat last night at Johnny Correno's. No motorcycle riding
for
me.
Oh yeah, Don is going to see the Dr. about something to help with his nerves
and
to stop smoking. He is going to tell him he is drinking with the stuff that
he
is taking. Maybe the Doc can give him something to help settle down all this
hostility.
I'll work on the inventory list tonight. You need to pull together all the
finical data, CD's etc. that are out and that we cashed in. Then we will
stick in new values. Also need to give a good fair market value on items we
are
selling so we do not have to pay tax on the stuff right. If we value the
place
at $175,000 and sell for less, then we don't have to pay taxes on the money,
so
I was told.
See Ya.
[email protected] on 10/24/2000 08:09:57 AM
To: Jerry W Germany
cc:
Subject: Yo
Update. Spoke with the lawyer yesterday. We can't buy Don out right now.
We need to turn in the final inventory list, get things resolved with Mary
(be it good or bad) then we can buy Don out.
She still thinks that we won't have any issues with Mary. After we provide
the inventory list, she wants me to meet with her (Joal), Mary, and Mary's
lawyer to see what we need to do to get this CONFLICT resolved. Joal
thinks we should be able to do this during the first 2 weeks of November.
I have a bad cold and I went scooter riding last night. Do you care?
I can't blame brother too much, I still bounce back and forth between major
frustration and apathy on the East Texas issue. Hope for the best!!
Later | 2024-06-15T01:26:28.774034 | https://example.com/article/5597 |
Q:
Converting Python objects to JavaScript for PyV8
I'm trying to pass Python data (lists, dicts, strings..., arbitrarily nested) to PyV8.
class Global(object):
def __init__(self, data):
self.data = data
ctx = PyV8.JSContext(Global([{'a':1}]))
ctx.enter()
res = ctx.eval('data.length')
js_len = PyV8.convert(res)
print js_len
The code above prints None, presumably because the data object is not transformed to a JSArray and thus data.length evaluates to undefined. Is there a reliable way to do the necessary conversion in PyV8 other than using JSON?
A:
Apparently PyV8 doesn't correctly convert python lists to Javascript arrays, which leads my_list.length to return undefined, which is getting converted to None.
ctx = PyV8.JSContext()
ctx.enter()
ctx.locals.a = [{'a':1}]
print ctx.locals.a
#> [{'a': 1}]
print ctx.eval("a.length")
#> None
print ctx.eval("a[0].a")
#> 1
ctx.locals.blub = {'a':1}
print ctx.eval("blub.a")
#> 1
print ctx.eval("Object.keys(blub)")
#> a
ctx.locals.blub = {'a':[1,2,3]}
print ctx.eval("Object.keys(blub)")
#> a
print ctx.eval("blub.a")
#> [1, 2, 3]
ctx.locals.blub2 = [{'a':[1,2,3]}]
print ctx.eval("blub2")
#> [{'a': [1, 2, 3]}]
print ctx.eval("blub2.length")
#> None
print ctx.eval("Array.isArray(blub2)")
#> False
print ctx.eval("typeof(blub2)")
#> object
print ctx.eval("blub2[0].a")
#> [1, 2, 3]
print ctx.eval("typeof(blub.a)")
#> object
print ctx.eval("Array.isArray(blub.a)")
#> False
The answer is to use PyV8.JSArray(my_list). I've written the following helper functions for my project that deal with various little problems and make it easy to convert back and forth between python and js objects. These are targeted at a specific version of PyV8 however (which is the only version I can recommend, see discussion in the linked issues), so your results may vary if you use them as-is. Example usage:
ctx.locals.blub3 = get_js_obj({'a':[1,2,3]})
ctx.locals.blub4 = get_js_obj([1,2,3])
ctx.eval("blub3.a.length")
#> 3
ctx.eval("blub4.length")
#> 3
And here are the functions.
def access_with_js(ctx, route):
if len(route) == 0:
raise Exception("route must have at least one element")
accessor_string = route[0]
for elem in route[1:]:
if type(elem) in [str, unicode]:
accessor_string += "['" + elem + "']"
elif type(elem) == int:
accessor_string += "[" + str(elem) + "]"
else:
raise Exception("invalid element in route, must be text or number")
return ctx.eval(accessor_string)
def get_py_obj(ctx, obj, route=[]):
def dict_is_empty(dict):
for key in dict:
return False
return True
def access(obj, key):
if key in obj:
return obj[key]
return None
cloned = None
if isinstance(obj, list) or isinstance(obj, PyV8.JSArray):
cloned = []
temp = str(access_with_js(ctx, route)) #working around a problem with PyV8 r429
num_elements = len(obj)
for index in range(num_elements):
elem = obj[index]
cloned.append(get_py_obj(ctx, elem, route + [index]))
elif isinstance(obj, dict) or isinstance(obj, PyV8.JSObject):
cloned = {}
for key in obj.keys():
cloned_val = None
if type(key) == int:
#workaround for a problem with PyV8 where it won't let me access
#objects with integer accessors
val = None
try:
val = access(obj, str(key))
except KeyError:
pass
if val == None:
val = access(obj, key)
cloned_val = get_py_obj(ctx, val, route + [key])
else:
cloned_val = get_py_obj(ctx, access(obj, key), route + [key])
cloned[key] = cloned_val
elif type(obj) == str:
cloned = obj.decode('utf-8')
else:
cloned = obj
return cloned
def get_js_obj(ctx,obj):
#workaround for a problem with PyV8 where it will implicitely convert python lists to js objects
#-> we need to explicitely do the conversion. see also the wrapper classes for JSContext above.
if isinstance(obj, list):
js_list = []
for entry in obj:
js_list.append(get_js_obj(ctx,entry))
return PyV8.JSArray(js_list)
elif isinstance(obj, dict):
js_obj = ctx.eval("new Object();") # PyV8.JSObject cannot be instantiated from Python
for key in obj.keys():
try:
js_obj[key] = get_js_obj(ctx,obj[key])
except Exception, e:
# unicode keys raise a Boost.Python.ArgumentError
# which can't be caught directly:
# https://mail.python.org/pipermail/cplusplus-sig/2010-April/015470.html
if (not str(e).startswith("Python argument types in")):
raise
import unicodedata
js_obj[unicodedata.normalize('NFKD', key).encode('ascii','ignore')] = get_js_obj(ctx,obj[key])
return js_obj
else:
return obj
| 2024-01-24T01:26:28.774034 | https://example.com/article/1755 |
The patient's journey with chronic hepatitis C from interferon plus ribavirin to interferon- and ribavirin-free regimens: a study of health-related quality of life.
Interferon and ribavirin negatively impact health-related quality of life (HRQL) during treatment. To compare the impact of interferon and/or ribavirin-containing regimens on HRQL to interferon- and ribavirin-free regimens. HRQL data from nine multinational phase 3 clinical trials of sofosbuvir (SOF)-based regimens with and without ledipasvir (LDV), pegylated interferon (IFN) or ribavirin (RBV) were used. The Short Form-36 (SF-36) HRQL questionnaire was administered to subjects prospectively at baseline, during treatment, and 12 and 24 weeks after treatment cessation. A total of 3460 CH-C with SF-36 data were included (52.2 ± 10.3 years, 62.6% male, 73.6% treatment-naïve, 15.0% cirrhotic, 68.2% HCV genotype 1 and 20.1% genotype 3). Compared to baseline HRQL, at the end of treatment, severe HRQL decrements were noted in IFN + RBV ± SOF regimens (on average, -3.8 to -24.3 on a 0-100 scale for different HRQL domains), while moderate decrements were noted in SOF + RBV ± LDV (-2.8 to -8.6). In contrast, in SOF/LDV without RBV, HRQL improvements were noted during treatment (+2.3 to +5.2). By 12 weeks post-treatment, HRQL returned to baseline in IFN + RBV ± SOF (P > 0.05) and improved in all IFN-free arms (+2.6 to +7.8). In multivariate analysis, a lower end of treatment HRQL was associated with IFN + RBV + SOF and a higher end of treatment HRQL was associated with SOF/LDV. By post-treatment-12, SOF/LDV was additionally associated with higher mental health scores. These improvements in HRQL scores were maintained 24 weeks post-treatment. Removing interferon and ribavirin has led to substantial improvement of health-related quality of life during treatment. This may result in better patient experience and higher adherence to treatment regimen. | 2023-10-17T01:26:28.774034 | https://example.com/article/3937 |
"The DOJ should have let the court appreciate and weigh the evidence, determine the relevance and the authenticity of the evidence presented," he added.
Sotto said Tan's case is a "very serious and urgent matter."
His proposed solution is the merging of the Dangerous Drugs Board (DDB) and the Philippine Drugs Enforcement Agency (PDEA) into a Presidential Drug Enforcement Authority, which will attack the drug problem through a more wholistic approach. | 2023-09-23T01:26:28.774034 | https://example.com/article/1632 |
Swellable-Nanogel-Injection Pilot in Mendoza Norte, Argentina
Despite the increasing attention paid to nanogels, there has been little research about the transfer of their properties to field pilots. The authors of the complete paper, SPE 184586, observe that nanogels increase their size faster than expected or produce aggregation leading to serious blocking problems at the sandface. This was observed in both coreflooding experiments and field pilot tests regardless of water composition. The addition of a certain concentration of surfactant slightly improves injectivity.
Introduction
The authors refer to a Chinese commercial system whose manufacturers describe the purpose of the treatment as the following:
To form a certain degree of injection resistance in the existing high-permeability water channels, to create a more-homogeneous reservoir
To displace the oil in the relatively low-permeability (oil-containing) regions by enlarging sweep area
To increase oil production and decrease water cut for the long term.
The key message is that nanospheres divert water flow deep in the reservoir from high-permeability to low-permeability regions.
The commercial system is a precrosslinked polymer that is commercialized as a nano-inverse emulsion (the continuous phase is oil). The precrosslinked polymer stays inside water drops that are stabilized by a surfactant and an external phase (oil).
The product application in the field is very simple. It consists of adding the nanogel emulsion to the injection water, which is an advantage because specific facilities are not needed.
To prepare the dispersion (2,000 ppm) of nanogel in the laboratory, the product is added to water under stirring at 700 rev/min at room temperature. A description of the product’s characteristics is provided in the complete paper.
Swellable-Nanogel-Injection Pilot
Reservoir Characteristics. Barrancas is a high-temperature (100°C) and medium-salinity reservoir. The reservoir is under waterflooding; currently, the recovery factor is approximately 27% at less than one pore volume of injected water. The reservoir is formed by conglomerates and sandy conglomerates. The trap is of the structural/stratigraphic type. The reservoir has four intervals (Green, Purple, Blue, and Red), with the following average properties:
Gross thickness: 60 m
Net pay: 25–20 m
Porosity: 17%
Permeability:
Green: 60 md
Purple: 30 md
Blue: 8 md
Red: 120 md
Injection Pilot. The nanogel-injection pilot began in December 2013 in the Barrancas Formation on injector Well B-342. The original design was the injection of 0.2 pore volumes in the array (1 year of injection, 30–40% active matter) to obtain a recovery factor increase of 6%.
The facilities are compact and easy to implement (Fig. 1; see image above). The dosing system placed in the well location has two high-pressure pumps (200 kg/cm2). There is a digital high-pressure flowmeter to control the nanogel injection.
There were two attempts to inject nanogel emulsion. In the first case, the rate was approximately 100 m3/d and the pressure 155 kg/m3. After the nanogel injection, the injectivity rate decreased very quickly. The strategy to prevent injectivity impairment was to diminish the product concentration. The first period lasted approximately 4 days and the pressure rode up to 190 kg/cm2, with an injection rate of 40 m3/d (in the same period, there were several injection downtimes). It was then decided to stop nanogel injection because of low injectivity. Later, several cleanups were carried out with chlorine dioxide, but the damage was not easily removed. Mud acid was subsequently employed to clean up the well.
In the second attempt, the injection rate was 140 m3/d and the pressure 135 kg/cm2. The same phenomenon occurred. After 5 days, the flow rate decreased to 35 m3/d and the pressure rose to 195 kg/cm2. The investigators failed to recover injectivity conditions previous to nanogel injection, and, during the intervention, produced gel flock from downhole.
Possible Causes of Injectivity Loss
The injectivity loss was highly influenced by the nanogel; the other wells in the area did not lose injectivity in the same proportion.
High nanogel concentrations were injected for a couple of hours because there were several injection downtimes in the injection.
The well never recovered the initial injectivity, even after the acid job, which may indicate that the damage was not easily removed.
The investigators suspected that the product did not meet specifications.
Even though the nanogel was designed to be compatible with the water salinity of Barrancas field, the water quality was not properly defined as the TSS (total suspended solids) and the total oil content.
Results
Step 1. The objective of this step was to validate the quality of product (nanogel emulsion). The conditions and the values of the product were the following:
The samples of stored emulsion were validated according to the manufacturer’s specifications. The average initial size was 60 nm at 25°C.
The viscosity of emulsion was within the manufacturer specified range.
The thermal stability test was good. No obvious changes were observed compared with initial properties.
Step 2. Although the product passed the quality test, it was important to evaluate what happened when the nanogel emulsion is dispersed into water.
The measured size for laser scattering was consistent with that observed on the microscope.
Although the product had an initial size of the nanometer order, the dispersion of nanogel, as was injected in the field, immediately increases its size to approximately the micrometer order. This behavior indicated that the size of the product had increased, the particles of nanogel were aggregated, or that the oil had remained dispersed in the water, interfering with the measurement.
Step 3. According to the manufacturer’s specifications for measuring the nanogel size, it is necessary to separate the oil phase with an organic solvent. Thus, the investigators added 2,000 ppm of the product in synthetic injection water and then put the aqueous solution in contact with the solvent (n-hexane) in a separating funnel.
The product, once dispersed and with its oil phase extracted, increases its size 3.5 times after 24 hours.
An appreciable change of size distribution was detected from Day 10.
The first dispersion with oil phase has larger sizes in the size distribution; this might be because of the oil drops’ contribution.
Step 4. Six coreflood experiments were carried out to evaluate the injectivity of product with different types of water. Five of them were performed on Berea sandstones (gas permeability = 100–200 md), and the sixth was performed on Bentheimer sandstone (gas permeability = 1.7 darcy). The coreflood tests were carried out with a constant flow rate at 70°C.
Berea 1. The pressure on the inlet increased 6 times over the reference value (filtered synthetic injection water) after being swept with 4 pore volume (PV). The pressure transducer located on the first tap did not show changes, indicating that the product was accumulating on the inlet face.
Berea 2. The pressure on the inlet increased 3.5 times over the reference value after being swept with 12 PV. The pressure transducer located on the first tap did not show changes, indicating that the product was accumulating on the inlet face.
Berea 3. The pressure on the inlet increased 16 times over the reference value after being swept with 16 PV. The pressure transducer located on the first tap showed a small increase after being swept with 11 PV. The water injection that followed in the flux direction tends to stabilize the pressure. The sweep is more unstable because of the interactions between the nanogel and suspended solids in the injection water.
Fig. 2—Inlet face of Bentheimer sandstone
after being swept with nanogel.
Berea 4. It was thought that the injectivity loss is caused by dispersed oil or the nanogel’s aggregates, so it was decided to perform a flow test that added surfactant. The pressure on the inlet increased 19 times over the reference value after being swept with 12 PV. The pressure transducer located on the first tap showed a small increase after being swept with 5 PV. The water injection that followed in the flux direction tends to stabilize the pressure and helps to reduce the inlet pressure approximately 20%.
Berea 5. A coreflood with the nanogel dispersion (having extracted the oil phase) was carried out in order to evaluate the influence of the oil in the injectivity loss. The pressure on the inlet increased 4.5 times over the reference value after being swept with 11 PV. The nanogel product without oil phase went through the porous media after 12 PV were injected. The pressure in the intermediate taps increased also 4.5 times; therefore, the oil phase contributed to the plugging.
Bentheimer. This sandstone was used to evaluate the injectivity of the nanogel product on a porous media of high permeability. The pressure on the inlet increased 12 times over the reference value (filtered synthetic injection water) after being swept with 8 PV. The inlet of the sandstone is shown in Fig. 2. The plugging caused by the product is clearly visible.
Conclusions
The size of preformed nanogel increases immediately when the nanogel emulsion is added to water. This issue must be considered to select and design a pilot in the field.
The oil in the nanogel dispersion (as small drops) interferes and increases the dispersion particle size.
The preformed nanogel increases its size over time and aggregates.
The inlet pressure raise was observed in every coreflood test, no matter the type of water. The sandstones were plugged, generating damage during the laboratory test.
The addition of surfactant improved the displacement on Berea sandstone slightly. This indicates that the surfactants in the formulation of nanogel product are not efficient enough to keep the nanogel dispersed by itself.
STAY CONNECTED
Don't miss out on the latest technology delivered to your email weekly. Sign up for the JPT newsletter. If you are not logged in, you will receive a confirmation email that you will need to click on to confirm you want to receive the newsletter. | 2024-06-09T01:26:28.774034 | https://example.com/article/9924 |
Deep endometriosis infiltrating the recto-sigmoid: critical factors to consider before management.
Deep endometriosis invading the bowel constitutes a major challenge for the gynecologist. In addition to the greater impact on pain, the high incidence of surgical morbidity involved with bowel endometriosis poses a therapeutic dilemma for the surgeon. Intestinal involvement by deep endometriotic nodules has been estimated to occur in 8-12% of women with endometriosis. Individual and clinical factors, pre-operative morphologic characteristics from imaging, surgical considerations and impact on quality of life are critical variables that should be considered in determining the best therapeutic strategy for a patient with deep endometriosis involving the sigmoid and/or the rectum. Pre-operative planning is fundamental for defining the optimal therapeutic strategy; patient counseling of treatment options, and when surgery is indicated, involvement of a multidisciplinary surgical team is required. The PubMed and Cochrane database were searched for all original and review articles published in English, French and Italian, until June 2014. Search terms included 'deep endometriosis', 'surgical and clinical approach', 'bowel disease', 'quality of life', 'management of deep endometriosis'. Special attention was paid to articles comparing features of discoid and segmental resection. The rationale for the best therapeutic options for patients with deep endometriosis has been shown and an evidence-based treatment algorithm for determining when and which surgical intervention may be required is proposed. In deciding the best treatment option for patients with deep endometriosis involving the sigmoid and rectum, it is important to understand how the different clinical factors and pre-operative morphologic imaging affect the algorithm. Surgery is not indicated in all patients with deep endometriosis, but, when surgery is chosen, a complete resection by the most appropriate surgical team is required in order to achieve the best patient outcome. In women with deep endometriosis, surgery is the therapy of choice for symptomatic patients when deep lesions do not improve with a medical treatment. | 2024-03-11T01:26:28.774034 | https://example.com/article/1513 |
INTRODUCTION {#s1}
============
KRAS mutations are among the most common alterations in human malignancies \[[@R1]--[@R3]\]. The KRAS pathway turns on proliferative signals and turns off pro-apoptotic signals, thereby driving cellular transformation such that the presence of oncogenic mutations in KRAS, EGFR and other genes alters signaling pathways and gene expression programs that control responses to particular therapies \[[@R4], [@R5]\]. Moreover, because sporadic malignancies are heterogeneous, understanding the molecular differences among cancer subtypes is required to develop precision therapies. This is the central challenge of molecular oncology.
Cellular transformation is a complex process involving activation of oncogenes and silencing of tumor suppressor genes (TSGs) \[[@R6]\]. Chromatin alterations are common hallmarks of cancer development and progression and are frequently linked to regulation of gene expression \[[@R7]\]. DNA methylation is among the best characterized epigenetic alteration linked to transcriptional silencing of TSGs in KRAS-mutated cancers \[[@R8]--[@R10]\]. Methylation of CpG dinucleotides in DNA is a dynamically regulated process that involves cytosine 5-methylation mediated by DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) \[[@R11]\] and active DNA demethylation initiated by the 5-mCpG hydroxylation activities of Ten-Eleven translocases (TET1, TET2, TET3) \[[@R12]\]. Dysregulation of DNMT and TET function is widespread in cancer especially with respect to TSG silencing \[[@R13]--[@R18]\].
According to a highly influential model, KRAS-induced DNMT1 transcription and resulting DNMT1 chromatin occupancy is the underlying cause of promoter hypermethylation and epigenetic silencing of multiple TSGs including *FAS* \[[@R8]--[@R10]\]. However, we discovered that KRAS transformation does not always transcriptionally induce DNMT1 when TSGs are hypermethylated and that KRAS-dependent suppression of TET1 is required for epigenetic silencing of TSGs \[[@R19]\]. Though we demonstrated that the ERK arm of the KRAS signaling pathway is responsible for TET1 repression, it was not clear how KRAS represses TET1 expression \[[@R19]\].
microRNAs (miRs) are short non-coding RNAs (20-30 nucleotides in length) that negatively regulate mRNA gene expression by targeting 3'-UTR sites \[[@R20]\]. miRNAs regulate diverse processes including cellular proliferation, differentiation and apoptosis and have been reported to function both as oncogenes and TSGs \[[@R21]--[@R23]\]. Oncogenic miRs can additionally be considered biomarkers associated with treatment options or emerge as cancer targets themselves \[[@R24]\].
Here we utilized pharmacogenomic approaches to identify miR-29b as a TET1- targeting miRNA that is upregulated by ERK activity. Inhibition of miR-29b restores *TET1* expression without affecting *DNMT1* levels. Moreover, knocking down miR-29b reactivates an array of TSGs that we found to be silenced by KRAS transformation. We further showed that an increase in *TET1* promoter occupancy and 5-hmC levels restores the epigenetic status and expression of targeted TSGs. Contrary to the expectation of the classical model of KRAS-driven DNMT1 expression \[[@R8]--[@R10]\], we established the presence of DNMT1 on TSGs promoters prior to oncogenic KRAS transformation with no change in DNMT1 occupancy following transformation. These mechanistic insights into reversible TSG hypermethylation in a pathway frequently altered in human cancer suggest a strategy for rational antagonism of miR-29b in tumors marked by high levels of miR-29b and low levels of TET1.
RESULTS {#s2}
=======
KRAS mutation induces miR-29b in an ERK-dependent manner {#s2_1}
--------------------------------------------------------
We previously discovered that KRAS-mediated TSG hypermethylation and silencing depends on down-regulation of the *TET1* mRNA. Suppression of *TET1* expression is mediated by the RAF-MEK-ERK pathway and not the PI3K-AKT pathway \[[@R19]\]. Here we aimed to identify the missing link between increased ERK activity and *TET1* suppression. As miRs are important regulators of signaling pathways in carcinogenesis, we hypothesized that a miR is up-regulated in KRAS-transformed cells that depresses expression of *TET1*. To identify miRs with the potential to regulate *TET1* that are induced by KRAS mutation in a MEK-dependent manner, we performed miR profiling with two cell lines. In HBEC3 cells, we identified the set of miRs that are up-regulated in stably KRAS-G12V transduced HBEC3 cells with respect to vector control. In addition, in KRAS-addicted H1299 cells, a MEK inhibitor PD98059 (20μM) was used to identify miRNAs downregulated by inhibition of KRAS-MEK-ERK signaling pathway with respect to a DMSO control. This approach led to identification of microRNAs which are commonly regulated by KRAS in two distinct cell lines. Among 6631 miRs analyzed, 47 are upregulated on KRAS transformation in HBEC3 cells and 53 are downregulated on PD98059 treatment in H1299 cells. Only 13 miRs were found to be commonly regulated in both cell lines (Figure [1A-1B](#F1){ref-type="fig"}). We further screened all miRs that were up in KRAS-transformed cells and down in PD98059-treated cells for the potential to target *TET1* mRNA using the microT-CDS prediction algorithm \[[@R25]\]. Though seven miRs upregulated by KRAS and 9 miRs downregulated by PD98059 were predicted to target *TET1*, miR-29b-3p was the only miR whose expression fulfilled all expression and predicted targeting criteria (Figure [1A](#F1){ref-type="fig"}).
{#F1}
To validate the microarray results, miR-29b expression was analyzed in HBEC3 and H1299 cell systems by quantitative RT-PCR. Consistent with transcriptomic analysis, KRAS transformation of HBEC3 leads to a 3-fold increased expression of miR-29b, while miR-29b is depressed nearly 4-fold by virtue of inhibition of MEK in H1299 cells (Figure [1C](#F1){ref-type="fig"}).
miR-29b induction represses TET1 expression and hydroxymethylation {#s2_2}
------------------------------------------------------------------
miR-29b belongs to a class of miRs reported to target epigenetic modifiers including DNMTs and TETs \[[@R26]\]. Induction of miR-29b by KRAS and the MAPK pathway was surprising in light of reports that miR-29b functions as a TSG, whose downregulation stimulates aberrant DNMT expression and carcinogenesis \[[@R27]--[@R31]\]. We therefore analyzed mRNA expression of methylating (*DNMT1, DNMT3a, DNMT3b*) and demethylating enzymes *(TET1, TET2, TET3)* as a function of antagomir-29b (AM-29b) treatment versus a negative control (NC) reagent. miR-29b expression was inhibited by 300 nM AM-29b in HBEC3-KRAS and H1299 cells ([Supplementary Figure 1](#SD1){ref-type="supplementary-material"}). We previously reported that KRAS transformation depresses expression of *TET1* and *DNMT3b* \[[@R19]\]. In HBEC3-KRAS cells, AM-29b restored expression of *TET1, TET3* and *DNMT3b* by 5-fold, 2-fold and 4-fold, respectively. Similar results were observed with H1299 cells (Figure [2A](#F2){ref-type="fig"}). AM-29b did not significantly alter expression of *TET2, DNMT1* or *DNMT3a* ([Supplementary Figure 1](#SD1){ref-type="supplementary-material"}).
{#F2}
Given the changes in expression of *TET1, TET3* and *DNMT3b* upon AM-29b treatment, we next investigated genome-wide 5-mC and 5-hmC levels in HBEC3-KRAS and H1299 cells. miR-29b downregulation resulted in a small but significant decrease in 5-mC levels in H1299 cells but not in HBEC3-KRAS cells. However, 5-hmC levels were significantly elevated in both cell lines upon miR-29b inhibition, indicating an overall increase in TET activity (Figure [2B](#F2){ref-type="fig"}).
Oncogenic miR-29b induction causes repression of lung TSGs {#s2_3}
----------------------------------------------------------
Lung squamous cell carcinoma (SCC) has been classified into three distinct subtypes based on gene enrichment profiles: basal/secretory, classical and primitive \[[@R4]\]. The basal/secretory subtype, also termed an immune evasion subtype, is enriched in MAPK signaling with miR-29b induction and *TET1* downregulation. To identify additional genes that are coordinately regulated by KRAS, ERK, miR-29b and TET1, we used GEO2R (<http://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE57083>) to mine expression data of 13 basal/secretory SCC cell lines versus 9 cell lines of the classical or primitive subtypes (Figure [3A](#F3){ref-type="fig"}). Focusing on TSGs, we analyzed expression of a set of 534 mRNAs depressed in lung SCC compared to normal lung in the Tumor Suppressor Gene database (<https://bioinfo.uth.edu/TSGene/>). As shown in [Supplementary Table 1](#SD1){ref-type="supplementary-material"}, we identified 44 genes that are significantly down-regulated in the basal/secretory subtype. For further validation in HBEC3 and H1299 cells, we selected 13 genes with more than one log fold-change of down-regulation in the basal/secretory SCC lines (Figure [3B](#F3){ref-type="fig"}).
![miR-29b dependent transcriptional suppression of TSGs downstream of KRAS transformation\
**(A)** Classification of lung cancer cell lines \[[@R4]\]. **(B)** Hierarchical clustering analysis of TSGs, whose mRNAs are depressed \>1 log fold- change in Group 1 cell lines with respect to Group 2. **(C)** TSGs are consistently depressed in KRAS-transformed HBEC3 cells with respect to controls (upper panel). The same genes are re-expressed upon AM-29b transfection (lower panel). **(D)** Bioinformatically identified genes are almost universally reactivated by PD98059 and AM-29b in H1299 cancer cells. **(E)** A Venn diagram depicts the high overlap of TSGs silenced by KRAS transformation, reactivated by PD98059 and restored by AM-29b. Data are presented as mean ± SD. \*p \< 0.05; \*\*p \< 0.01; \*\*\*p \< 0.001 in comparison to control cells.](oncotarget-08-74755-g003){#F3}
As shown in Figure [3C](#F3){ref-type="fig"}, nearly all of these genes are down-regulated by KRAS-transformation in HBEC3 cells and restored by AM-29b. Similarly, most are increased in expression by PD95059 and AM-29b in H1299 (Figure [3D](#F3){ref-type="fig"}). Thus, miR-29b is an important mediator of KRAS-dependent TSG silencing in human basal/secretory lung cancer.
miR-29b inhibition reverses hypermethylation-mediated silencing of *MGMT* and *DAPK* genes in KRAS-transformed cells {#s2_4}
--------------------------------------------------------------------------------------------------------------------
We previously reported that epigenetic silencing of three TSGs (*DAPK, MGMT* and *DUOX1*) caused by KRAS-driven promoter hypermethylation is a function of repressed expression of *TET1* \[[@R19]\]. Identification of miR-29b as a factor that depresses *TET1* expression in KRAS-transformed cells suggested the possibility of reversing TSG silencing with a drug modeled after AM-29b. To test the cellular basis of this hypothesis, HBEC3-KRAS cells were transfected with AM-29b and the mRNA levels of *MGMT, DAPK* and *DUOX1* were analyzed. As shown in Figure [4A](#F4){ref-type="fig"}, miR-29b inhibition restores mRNA accumulation of *MGMT* and *DAPK* without affecting steady-state levels of *DUOX1*. To test whether a decrease in promoter methylation is responsible for restored gene expression, we examined the promoter methylation status of *MGMT* and *DAPK* genes by quantitative methylated DNA immunoprecipitation (MeDIP). As shown in Figure [4B](#F4){ref-type="fig"}, AM-29b treatment produces a significant decrease in *MGMT* and *DAPK* promoter methylation, indicating that miR-29b drives reversible TSG silencing via increasing net DNA methylation. The results of MeDIP assay were confirmed by bisulfite sequencing. Analysis of 39 and 24 CpG sites in the *MGMT* and *DAPK* promoters revealed a 1.8- and 2.7-fold decrease in promoter methylation following AM-29b treatment in KRAS-transformed cells, respectively (Figure [4C](#F4){ref-type="fig"}). Together, our data indicate that KRAS-directed epigenetic silencing of *MGMT* and *DAPK* occurs *via* a hypermethylation mechanism that can be reversed by miR-29b inhibition.
{#F4}
Reduction in TET1-mediated DNA demethylation is responsible for increased promoter methylation {#s2_5}
----------------------------------------------------------------------------------------------
We and others have established that decreased TET1 expression in response to oncogenic KRAS, MAPK or EGFR signaling is responsible for TSG silencing \[[@R4], [@R19], [@R32]\]. However, the standard model of KRAS-induced hypermethylation emphasizes the role of induced expression of DNMT1 as the driver of this phenomenon \[[@R8]\]. To test whether demethylation induced by miR-29b inhibition is caused by restored TET1 activity, we quantified 5-hmC modifications in the *MGMT* and *DAPK* promoters with TET-assisted bisulfite sequencing (TAB-seq). As shown in Figure [5A](#F5){ref-type="fig"}, KRAS transformation produces a decrease in promoter 5-hmC modifications and AM-29b treatment reverts this effect. The extent of 5-hmC modifications was more than doubled from 3.3% to 8.3% and 7.8% to 17.5% in the *MGMT* and *DAPK* promoters upon miR-29b inhibition, respectively. To test the hypothesis that KRAS-driven methylation of these genes is caused by decreased TET1 binding to their promoters, TET1 chromatin immunoprecipitation (ChIP) was performed. As shown in Figure [5B](#F5){ref-type="fig"}, KRAS transformation clearly depresses TET1 occupancy of these promoters, which was restored by AM-29b treatment.
{#F5}
The standard model of KRAS-driven TSG silencing states that DNMT1 and other RAS epigenetic silencing factors (RESEs) are not present on target gene promoters prior to KRAS transformation \[[@R8]\]. However, our data indicated that target gene promoters are enriched in *5-hmC prior to KRAS transformation* and that DNMT1 expression is not induced by KRAS in systems that nonetheless exhibit KRAS-driven TSG methylation \[[@R19]\]. We reasoned that the TET product 5-hmC cannot be present if the TET1 substrate 5-mC is not there first. According to this view, genes subject to KRAS-driven TSG methylation are dually occupied by DNMT1 and TET1 prior to activation of the MAPK pathway. Activation of the MAPK pathway would lead to miR-29b induction and TET1 repression, leading to net DNA methylation secondary to the loss of TET1-dependent active DNA demethylation.
As shown previously, KRAS transformation does not alter expression of *DNMT1* or *DNMT3a* in HBEC3 or H1299 cells \[[@R19]\], while *DNMT3b* expression is depressed by *KRAS* transformation and restored by miR-29b inhibition (Figure [2A](#F2){ref-type="fig"}). To test the hypothesis that DNMT1 is already present on KRAS-, miR-29b- and TET1-regulated promoters, we performed DNMT1 ChIP. Whereas TET1 is responsive to KRAS transformation and miR-29b antagonism (Figure [5B](#F5){ref-type="fig"}), DNMT1 is not: it is simply present on KRAS-regulated promoters. Thus, we demonstrated not only that miR-29b mediates KRAS-driven TSG silencing but that net methylation of *MGMT* and *DAPK* promoters is due to evacuation of TET1 from promoters that have DNMT1 and TET1 present prior to KRAS activation. The results are graphically summarized in Figure [6](#F6){ref-type="fig"}.
{#F6}
DISCUSSION {#s3}
==========
Lung cancers kill more people than tumors initiating in any other organ system \[[@R33], [@R34]\]. Most such malignancies occur after years of tobacco carcinogenesis and involve many altered genes \[[@R35], [@R36]\]. EGFR and KRAS mutations are the most common and mutually exclusive mutations in malignancies of the lung \[[@R37], [@R38]\]. Because KRAS is an effector of EGFR, the EGFR-RAS-RAF-MEK-ERK cascade is considered a target-rich environment for medical management of lung cancer \[[@R37], [@R39]--[@R41]\]. Whereas genetic alterations reveal oncoprotein targets, we also appreciate that the same signaling pathway turns off an abundance of TSGs via gene silencing. Nucleoside-based DNA demethylating agents, such as 5-aza-cytidine, reactivate hypermethylated TSGs via trapping DNMTs for subsequent proteolytic elimination \[[@R42]\]. Direct inhibitors of DNMT1 have recently been reported \[[@R43]--[@R45]\]. However, there are only limited data showing that DNMT1 can be targeted with such compounds for the prevention or treatment of cancer \[[@R46]\].
The concept of RESE suggested that factors in addition to DNMT1 might be targetable in malignancies with MAPK activation \[[@R8]\]. However, we have shown that KRAS-driven hypermethylation and gene silencing can occur without induction of the DNMT1 mRNA or protein and that the gene silencing depends on repression of TET1 \[[@R19]\]. This led us to search for a RESE that is downstream of MAPK activation and required for TET1 repression. Such a molecule, if antagonizable, could potentially emerge as a target to reactivate TSGs downregulated in common human malignancies \[[@R47]--[@R49]\].
Here we show that the KRAS and MAPK pathway induces miR-29b expression leading to *TET1* suppression and epigenetic silencing of genes such as *DAPK* and *MGMT* in KRAS-transformed lung cells. Contrary to the predictions of the classical model of KRAS-driven TSG methylation \[[@R8]\], these genes are occupied by DNMT1 and TET1 prior to KRAS transformation and gain net methylation due to relief of TET1-dependent hydroxymethylation. Our data indicate that miR-29b downregulates a set of TSGs that contribute to transformation by KRAS and that these genes can be identified using bioinformatic approaches.
In the basal/secretory subtype of lung SCC, the ETS1 transcription factor drives expression of miR-29b \[[@R4]\]. In addition, oncogenic EGFR signaling was reported to induce expression of transcriptional repressor YY1 and down-regulate expression of CEBPA in order to repress TET1 \[[@R32]\]. However, because we discovered that CEBPA is re-expressed upon miR-29b antagonism (Figure [3](#F3){ref-type="fig"}), it is not clear that CEBPA acts upstream of TET1.
Discovery of miR-29b in an oncogenic context was surprising in view of its earlier characterization as a TSG in lung \[[@R31]\] and other malignancies \[[@R27], [@R28]\]. Our results were particularly surprising in that miR-29b was reported to downregulate DNMT3A and DNMT3B directly \[[@R31]\] and DNMT1 expression indirectly \[[@R28]\]. However, we found no changes in *DNMT1* or *DNMT3A* expression following miR-29b inhibition. Whereas *DNMT3B* expression does increase upon miR-29b inhibition, this does not appear to be consequential to KRAS-driven TSG silencing as one would either expect DNMTs to be overexpressed when the KRAS pathway is on \[[@R8]\] and/or to find that DNMT-opposing TETs are repressed when the KRAS pathway is on \[[@R19]\]. Moreover, we are not alone in identifying miR-29b as an oncogene in lung cancer as its expression has been shown to protect KRAS-transformed lung cells from apoptosis by inducing the NF-κB pathway \[[@R5]\].
As shown in Figure [3](#F3){ref-type="fig"}, our data show that miR-29b antagonism is effective in restoring TSG expression in KRAS-activated cancer cells and identify cancer gene expression subtypes that rationalize AM-29b drug development. Naturally, in malignancies in which miR-29b is instead a TSG, miR-29b would not be a target. We suggest that the gene set enrichment methods \[[@R4]\] that were expanded herein be used to identify tumors that are responsive to miR-29b antagonism. Ideally, this transcriptomic analysis should include mRNAs and miRNAs so that one can see *ETS-1* and miR-29b increased with *TET1* decreased as a subtype of cancer that could be opposed by miR-29b antagonism. In addition, because tumors with inactivated miR-29b would not be positive for miR-29b in a liquid biopsy, a simple approach to identify candidates for miR-29b antagonism would be to screen for elevated circulating miR-29b and any other biomarker(s) of MAPK hyperactivity in liquid biopsies.
MATERIALS AND METHODS {#s4}
=====================
Cell lines {#s4_1}
----------
Vector or KRAS-G12V transduced HBEC3 cells were cultured in keratinocyte serum-free media supplemented with bovine pituitary extract and recombinant human EGF. H1299 cells were cultured in RPMI-1640 media supplemented with 10% fetal bovine serum.
miRNA array {#s4_2}
-----------
miRNA profiling was performed with an Affymetrix GeneChip miRNA 4.0 array. RNA integrity number was \> 9 for all samples. The Affymetrix Expression Console and Transcriptome Analysis Console software 3.0 were used to analyze raw data and generate heat maps. miRNA profiling data have been deposited to the NCBI Gene Expression Omnibus, accession number GSE100857.
RNA isolation and real-time qPCR {#s4_3}
--------------------------------
Total RNA was isolated using the mirVANA miRNA isolation kit (Ambion, Life Technologies). For miRNA analysis, cDNA was synthesized using TaqMan MicroRNA Reverse Transcription Kit (ThermoFischer Scientific) and miR-29b/U6 expression was quantified using TaqMan MicroRNA Assays (ThermoFischer Scientific). mRNA expression of target genes was determined using iScript cDNA Synthesis Kit and iQ SYBR Green Supermix (Bio-Rad) on a CFX96 Real-Time PCR Detection System (Bio-Rad). Primer pairs used in mRNA expression analysis are listed in [Supplementary Table 2](#SD1){ref-type="supplementary-material"}.
Transfection {#s4_4}
------------
AM-29b and NC reagents were purchased from ThermoFisher Scientific. Cells were transfected with 300 nM AM-29b or NC using the Lipofectamine RNAiMAX Reagent (Invitrogen) and harvested after 72 h.
ChIP and MeDIP {#s4_5}
--------------
ChIP was performed using a Pierce Magnetic ChIP Kit (ThemoFisher Scientific) as instructed. Ten percent of digested chromatin was saved as input. TET1 and DNMT1 antibodies were purchased from Active Motif (61443) and Santa Cruz Biotechnology (sc-10219), respectively. MethylMiner Methylated DNA Enrichment Kit (ThemoFisher Scientific) was used for methylation analysis at TSG promoter regions. Genomic DNA was isolated using DNeasy Blood and Tissue kit (QIAGEN) and fragmented to an average size of 400 bp using a Covaris S2 sonicator. Immunoprecipitated DNA was analyzed by qPCR using primers listed in [Supplementary Table 2](#SD1){ref-type="supplementary-material"}.
Bisulfite and TAB sequencing {#s4_6}
----------------------------
EpiTect bisulfite kit (QIAGEN) was used for bisulfite treatment of genomic DNA. Treated DNA was amplified using gene specific primers ([Supplementary Table 2](#SD1){ref-type="supplementary-material"}). PCR products were run on 2% agarose gels and purified using QIAquick Gel Extraction Kit (QIAGEN). Purified products were cloned into the pGEM-T easy vector (Promega) and individual clones were then selected for sequencing. Methylation status of individual CpGs was assessed using the QUMA tool (<http://quma.cdb.riken.jp>). To detect 5-hmC modifications, genomic DNA was fragmented to an average of 400 bp by sonication. To protect 5-hmC modifications, fragmented DNA was treated using a TAB-seq Kit (WiseGene). Treated DNA was then subjected to bisulfite conversion, amplification, cloning and sequencing as above.
5-mC and 5-hmC quantification {#s4_7}
-----------------------------
Genomic DNA was isolated from AM-29b or NC transfected HBEC3-KRAS and H1299 cells. One hundred nanograms of DNA was used to determine global methylation and hydroxyl methylation levels using 5-mC and Quest 5-hmC DNA ELISA Kits (Zymo Research), respectively.
Statistical analysis {#s4_8}
--------------------
Data were analyzed using GraphPad Prism software 7.0a. p-values were calculated using two-tailed Student's t-tests and were considered to be significant if less than 0.05. All data were presented as mean ± SD.
SUPPLEMENTARY MATERIALS FIGURE AND TABLES {#s5}
=========================================
**Author contributions**
ST and CB designed the experiments. ST performed the experiments. ST and CB analyzed data and wrote the manuscript.
We thank the Genomics Division of the Iowa Institute of Human Genetics for miRNA profiling and thank Bo-Kuan Wu for helpful advice.
**CONFLICTS OF INTEREST**
The authors declare no conflicts of interest.
**FUNDING**
This work was supported by the Roy J. Carver Charitable Trust.
| 2024-02-14T01:26:28.774034 | https://example.com/article/7353 |
Q:
How do I change text alingment in DOORS?
Question
Within a single DOORS object, how do I change the text alignment from any menu or tool option? I am using DOORs 9.5.
Research
The first result on google only talks about soft versus hard returns, this prominent IBM Jazz page doesn't talk about an application I use and this answer from the IBM community requires DXL usage, which my team does not have permission to access. I am simply looking for the option that changes text alignment.
A:
A couple of ways: First the Object Text needs to be in Edit-In-Place.
1) From the toolbar press the indent icon..
2) From the menu:
Edit>In-Place>Increase (or) Decrease Indent
in DXL, the command is applyTextFormattingToParagraph(),
Hope this helps..
Don
| 2024-01-03T01:26:28.774034 | https://example.com/article/9441 |
Tuesday, 27 January 2015
Dr google
Hi,A patient came in today with calf pain he had had for a week after falling off of his bike. After a google to come up with the possible causes for this, he was adamant that he had acute compartment syndrome. This is a medical emergency where the trauma to the limb causes so much swelling it cuts off the blood supply, meaning the tissue becomes more damaged and inflamed due to to the lack of blood. A vicious circle. His leg looked completely normal.It took me a very long time to try and convince him that Dr google was not in an ideal position to assess his leg, and if he did have acute compartment syndrome his leg would have destroyed itself by now. After 30 minutes of my time he left to try some paracetamol and rest. | 2023-11-19T01:26:28.774034 | https://example.com/article/5482 |
As a leading girls’ school in Australia, St Catherine’s is committed to nurturing and empowering independent and globally responsive young women, enabling them to approach all their endeavours with confidence, wisdom and integrity. – St Catherine’s School Charter
As a School community, we help students find their sense of purpose in the world through an environment that integrates critical awareness, a social conscience and quality relationships. We inspire our students to not only own their learning but also understand and appreciate their own unique capacities and the world around them.
Boarding at St Catherine’s School provides our girls with a safe and comfortable living environment. They have the opportunity to make friends with girls from across Australia and around the world. Boarders are provided the freedom to socialise with friends and to explore Melbourne on organised weekend activities, as well as the opportunity to develop positive study habits and importantly, to have a lot of fun!
St Catherine’s prides itself on being a cohesive and unique School community. Current St Catherine’s families, along with our alumnae, future students, and current and past parents and staff, are all active, generous, enthusiastic and supportive members of the St Catherine’s School community.
Browse our latest news items, see what events are coming up, read what our teachers and Principal are writing about on Conscientia St Catherine’s Blog or be informed on the latest media coverage of St Catherine’s School.
Early Learning Centre – Campbell House: The Ilhan Family Centre
Sophie Mirabella
Sophie Mirabella
B.Comm LLB (Melb) LLM (Melb)
Sophie Mirabella (Panopoulos ’86) was born in 1968 to Greek migrant parents and learnt the value of hard work and entrepreneurial spirit by working after school and on weekends in the family milk bar from the age of 12.
Sophie Mirabella (Panopoulos ’86) was born in 1968 to Greek migrant parents and learnt the value of hard work and entrepreneurial spirit by working after school and on weekends in the family milk bar from the age of 12.
After School, she studied Law and Commerce at the University of Melbourne and worked as a solicitor and then barrister.
Sophie was a leading spokesperson against the push for an Australian republic as an elected delegate to the Australian Constitutional Convention in February 1998. In 2001, she was elected the Federal Member for Indi, a large and diverse electorate centred around Wangaratta.
Sophie married Greg Mirabella in June 2006, and the couple have two daughters, Alexandra and Katerina.
In 2008 Sophie was appointed Shadow Minister for Early Childhood Education, Childcare, Women and Youth and in 2009 was promoted to the Shadow Cabinet as Shadow Minister for Innovation, Industry and Science.
After losing the seat of Indi in the 2013 Federal Election, Sophie was appointed a Public Policy Fellow at the University of Melbourne and a Director of the Australian Submarine Corporation before deciding to re-contest the seat of Indi at the 2016 election. | 2024-05-26T01:26:28.774034 | https://example.com/article/8511 |
Donald Trump’s favorite “news” organization released a poll on Thursday, and it has very bad news for the president ahead of 2020.
According to the Fox News survey, each of the leading Democratic contenders polled – Joe Biden, Bernie Sanders, Elizabeth Warren and Kamala Harris – would easily defeat Trump if the election were held today.
The full breakdown of head-to-head polling via Fox News:
The Democrats are surging and Trump continues to sink
Like just about every piece of polling data we’ve seen this cycle, Biden polls strongest against Trump, beating him by 12 points in a hypothetical matchup. Sanders, too, continues to hold up well against the president with a 9-point lead.
The biggest shift comes in Trump’s head-to-head numbers against Warren and Harris, who now have solid leads after being behind in the last Fox News poll.
Democratic pollster Will Jordan pointed out how each of the Democratic candidates have surged since the last survey:
The Republican brand is in the tank
There is no question that this is a horrendous poll for Trump. Not only is he losing badly to the leading Democratic contenders, but his approval rating appears to be in a tailspin.
But it’s not just Trump who should be concerned. The survey shows the entire Republican brand is in the tank. The American people simply don’t want to be associated with the GOP.
While former President Obama, all the leading Democratic candidates and the Democratic Party as a whole have net positive favorability ratings, Trump, Mike Pence, the NRA and the Republican Party as a whole are underwater.
Sean Colarossi currently resides in Cleveland, Ohio. He earned his Bachelor of Arts degree in Journalism from the University of Massachusetts Amherst and was an organizing fellow for both of President Obama’s presidential campaigns. He also worked with Planned Parenthood as an Affordable Care Act Outreach Organizer in 2014, helping northeast Ohio residents obtain health insurance coverage. | 2024-06-11T01:26:28.774034 | https://example.com/article/2737 |
The Wolverines are playing for the NCAA Tournament National Championship for the first time in 20 years, but before that drought, they had been a fairly regular fixture on the sport's largest stage.
Michigan played for at least one title in the 1960s, '70s, '80s and '90s.
From Cazzie Russell to Rickey Green to the Fab Five, the Wolverines have had some special players and teams make historic runs in the NCAA Tournament.
Here's a look back at all of the Wolverines' appearances in the title game.
1965
In the first 25 years of the NCAA Tournament, from 1939-63, the Wolverines managed to secure an invitation to the field just once, in 1948. Then Cazzie Russell stepped on the court, and everything changed.
When Russell was a sophomore, in 1964, he and All-American Bill Buntin led the Wolverines to a Big Ten Championship and the school's second-ever appearance in the NCAA Tournament. Michigan lost to Duke, 91-80, in the Final Four.
But the next year, the Wolverines were back with a vengeance. After winning the Big Ten outright, they won their first three games in the NCAA Tournament by an average of 15.0 points per game, setting up a National Championship Game against the budding UCLA dynasty.
The Bruins won, 91-80, claiming their second consecutive national championship. They would eventually go on to win nine titles in a 10-year span under legendary coach John Wooden.
UCLA jumped out to an early lead, led by a game-high 42 points from star Gail Goodrich. Three Michigan starters - Buntin, Oliver Darden and Larry Tregoning - fouled out of the game, which is still a record in an NCAA Tournament game.
According to a Eugene Register-Guard story from the game, UCLA fans in attendance began chanting, "AP, UPI, Sports Illustrated bah, humbug," because those three wire services had tapped Michigan as the No. 1 team in the nation heading into the tournament.
"I felt our best chance was to fight them on the boards," Wooden said after the game. "I felt our quickness and speed could cause them to tire. I thought our press would eventually get to them."
1976
After Russell's final season (1966), the Wolverines took a bit of a dip, making the tournament just twice in the next 10 seasons (1974, 1975). But led by point guard Rickey Green, the Wolverines made a run to the title game in 1976.
There were some questions about Michigan leading into the NCAA Tournament. The Wolverines had faced four ranked teams during the regular season - and lost every time. But, like the 2013 team, they got hot at the right time, defeating Wichita State (74-73), Notre Dame (80-76), Missouri (95-88) and Rutgers (86-70) to reach the National Championship Game.
Like the program's first appearance in the title game, Michigan ran into a buzzsaw when it hit the championship game.
Indiana won the game, 86-68, capping an incredible two-year run. The Hoosiers finished the year with a perfect 32-0 record (the last undefeated champion in college basketball) and went 62-1 over the 1975 and '76 seasons (losing to Kentucky in the 1975 regional finals).
The Wolverines jumped out to a 35-23 lead at half, but Wayman Britt and Phill Hubbard each picked up a fourth foul early in the second half, helping the Hoosiers' offense. Indiana scored 63 second-half points to pull away.
"We played a very good first half," Michigan coach Johnny Orr said after the game. "But we got into foul trouble, and when we needed the big shots, we couldn't make them."
It was the first time in NCAA Tournament history that two teams from the same conference played for the championship.
1989
There is one enormous banner hanging from the south end of Crisler Arena - and it immediately grabs your eyes as you enter the bowl from the concourse. It says, "NATIONAL CHAMPIONS - 1989."
Led by Glen Rice, Rumeal Robinson and Loy Vaught, the Wolverines finished third in the Big Ten and received a No. 3 seed heading into the NCAA Tournament.
Then, the unimaginable happened: coach Bill Frieder announced that he would accept the Arizona State job at the end of the season. Then-athletic director Bo Schembechler famously announced that "a Michigan Man would coach Michigan" and dismissed Frieder from the team, naming Steve Fisher interim coach for the postseason.
Fueled by a rousing motivation speech from Schembechler, the Wolverines, who had lost their final game of the regular season 89-73 to Illinois, stormed into the NCAA Tournament.
The Wolverines won their first four games in the tournament by an average of 14.0 points per game, setting up a rematch with Illinois in the Final Four. Despite losing both regular-season games to Illinois by a combined 28 points, the Wolverines escaped the Illini, 83-81, to reach the National Championship Game, where they played Seton Hall.
In one of the most iconic moments in NCAA Tournament history, Robinson hit two free throws - one to tie, one to go ahead - in the waning seconds of the game, sealing Michigan's first - and to this point, only, NCAA Championship.
1992
Fab Five. Those two words have taken on a life of their own.
In 1991, five freshmen - Chris Webber, Jalen Rose, Juwan Howard, Jimmy King and Ray Jackson - took the college basketball world by storm, and led the Wolverines to a 25-9 record and the National Championship Game.
In the tournament, the Wolverines beat Temple (73-66), East Tennessee St (102-90), Oklahoma State (75-72) and Ohio State (75-71 in overtime) to reach the Final Four. After a 76-72 win over Cincinnati in the national semifinal, Michigan was back in the title game.
The freshmen of Michigan were outpaced by a veteran-laden Duke team, 71-51.
The Blue Devils captured their second consecutive title, the first time since UCLA dynasty of the 1960s and early 1970s that a team achieved that feat.
"We just played with more emotion in the second half," Duke coach Mike Krzyzewski said after the game. "In the first half, we played good defense, too. But they scored off our turnovers and they scored off defensive rebounds. It's just that our offense helped us out in the second half."
Rose hit a shot with just under seven minutes to go in the game, cutting the Duke lead to 48-45 - and then the Blue Devils took over.
Duke scored on the next 12 possessions to take control of the game.
1993
For the second year in a row, the Fab Five led the Wolverines to the National Championship Game. And for the second year in a row, Michigan came up just short.
Early a No. 1 seed in the NCAA Tournament, Michigan beat Coastal Carolina (84-53), UCLA (86-84), George Washington (72-64), Temple (77-72) and Kentucky (81-78) to get to the title game. Interestingly, the Wolverines beat the Wildcats despite going 0-of-4 from three-point range.
The title game against North Carolina is remembered for one thing: Webber's infamous timeout. Webber advanced up the court, drove into the corner and called a timeout, despite the fact that Michigan had none remaining. The technical foul was the nail in the coffin, and the Tarheels went on to win, 77-71.
2013
After a 20-year hiatus, the Wolverines are back in the National Championship Game. | 2024-05-16T01:26:28.774034 | https://example.com/article/4276 |
# Copyright 2020 Pants project contributors (see CONTRIBUTORS.md).
# Licensed under the Apache License, Version 2.0 (see LICENSE).
python_library()
python_tests(name='tests')
| 2023-09-24T01:26:28.774034 | https://example.com/article/6729 |
UPDATE THURSDAY: Lufthansa strike kicks in, no end in sight to dispute
Lufthansa cabin crew on Thursday formally started a 48-hour strike, forcing the airline to cancel hundreds of flights.
The German airline failed to quash the strike before it started. Frankfurt's labor court and the Hesse region's labor court — acting as an appeal court — ruled that the cabin crew trade union UFO had legally called on its members to stage the stoppage.
Lufthansa canceled 1,300 out of 6,000 flights scheduled — 700 on Thursday and 600 on Friday. The industrial action mostly affect flights departing from Germany.
'Refusal' to negotiate
The airline based its injunction by questioning the voting procedure used among UFO members to decide on industrial action.
UFO planned the warning strike to press Lufthansa for additional allowances at wage negotiations, citing what it claimed was management's "ongoing refusal" to negotiate.
Passengers who had booked flights between German airports could turn their tickets into rail tickets in an online procedure, Lufthansa announced after the rulings.
Staff want better conditions
The union had on Monday called on Lufthansa cabin crew to prepare for the strike, demanding better pay and conditions.
"This will affect all Lufthansa flights scheduled to leave from airports in Germany," the deputy chairman of the UFO cabin crew union, Daniel Flohr, said in a statement.
Disruptions also threatened Lufthansa's affiliate airlines, including Eurowings and SunExpress.
ed, ls,jsi,ipj/rc (dpa, Reuters)
Each evening at 1830 UTC, DW's editors send out a selection of the day's hard news and quality feature journalism. You can sign up to receive it directly here. | 2024-01-22T01:26:28.774034 | https://example.com/article/9251 |
Following that post, for every email we received that said Wow, that's fantastic - good on her and good on you for helping her achieve that! we received 3 or 4 others that had the air of frustration Why not me? Why can't I improve like that? In fact such was the response that we followed up with this post...
A key part of achieving that consistency is your swimming demeanour. Megan puts it this way:"I do know that I felt a big difference when I started swimming Wednesday mornings. I am not sure whether Wednesday improved my CSS or not but it definitely increased my confidence – 1 km TT? *shoulder shrug* … sure, whatever :-)"Megan's not saying that out of bravado, that really is how she thinks. When was the last time you really shrugged at a swimming time-trial? The key to improving is not to over-analyse or procrastinate but, like Megan, come to terms with the work you need to consistently do, switch off the brain and get on with it.If you can face your training with an inner smile rather than an inner grimace you've got everything you need to be the next Megan. Don't fear the hard work but actively embrace it - that is the attitude of a true champion.
Nick gives Rob a hearty high-five for leading a solid 400m interval!
In the Perth squads in Perth, when we're passing out the beepers (Tempo Trainer Pros) to swimmers to lead the lane during a hard set, we receive far more looks that say "No, not me - anyone but me!" than "Yes, what the hell, I'll give it a go!"... And this is Australia, famous for the digger spirit and can-do attitude!
The reality is that "just giving it a go" is what it's all about. As we say in Western Australia "We're not racing for sheep stations" - a solid workout that gets the heart pumping, blows the cobwebs out and has you thinking about how best to maintain your technique is what you are after. Being fit and active is way better than being unfit and thinking of where you once were! Yesterday is gone, only what you do right now is important, so give it a go!
Mike's quite happy to be following…for now -but when he gets back on front, watch out!
Training within a squad is a wonderfully motivating environment, challenging you to always be a better version of yourself. It doesn't matter about anyone else in your lane and yet at the same time it totally does!
A sense of camaraderie and team spirit can lift you on the flattest of days but if you are unwilling to take the beeper and share leading the lane, then you can't get upset, grumpy and see the "red mist" if the person leading doesn't hold exactly the pace that is set for the lane - that's rule 1 of swim squad! They're giving it their best shot and this is all anyone can ask on any given day. You should take that beeper knowing this is all anyone expects - whatever happens you're not letting anyone else down because you took the onus. If you "fail" so what? Does it really matter? No. Learn from it and pass the beeper on! It's fun, or should be!
Froomy
Chris Froome has just won his third Tour de France title against some pretty challenging odds. Nairo Quintana was his supposed rival, and yet he was never in the picture. Why? Because he was playing a game of defence, a game of safety, never willing to take the risk of an attack, always hoping Froome would eventually crack.
He didn't. Quintana lost. Convincingly.
Are you playing a game of defence with your swimming? Never willing to stretch yourself for fear of failure?
Leading the lane using a beeper is one obvious example of this but whether you're training with a beeper or not, whether you're in a squad or training solo, you need to get comfortable with the idea of going for something without holding back, without a safety net in place. You might make the set or the turnaround times, or you might not. You might set a massive PB or crash and burn. Win, lose or draw, the last thing you should do is fear the challenge.
It's amazing what you can achieve if you can get out of the way and just let yourself!
5 comments:
1. I feel like the Swim Smooth success stories always involve people going from 2:xx/100m swimmers to 1:3x/100m swimmers.
This is great... but generates no passion or interest for people who are perpetual 1:3x swimmers and desire to be a 1:20 or 1:15 swimmer! Tell me more, much more, about those you've helped make this sort of jump!
2. tempo trainers feature prominently in many posts. Often along with the hint of using the device to angle toward higher stroke rates.
I've got the issue of the slower my stroke goes, the faster I go. 58st/min is 1:30pace, while 61st/min is 1:34. Open water or pool (can't speak to serious waves however) this has held true. Yes, I've got long arms relative to height. Accordingly, my need for a tempo trainer doesn't seem high. Keep rate feeling slow, I'll go fast.
Thanks for responding Paul! I've got a +7 ape index and at 146lbs and 6 ft. I'm not floaty like Kate. Too high up feet not an issue for me. I get max sustainable speed at about 62 SPM (~1:30), going faster SPM currently slows me (1:33+).
Will try experimenting with straight arms. I'd love the 'swim with Perth squad' solution that worked for Kate, but that is not a commute that is doable for me. If/when you've got a Vancouver BC squad I'll be there! | 2023-11-05T01:26:28.774034 | https://example.com/article/5151 |
1. Field of the Invention
The present invention relates to an optical film, a liquid crystal panel, and a liquid crystal display apparatus. The present invention more specifically relates to an optical film suitable for a liquid crystal display apparatus providing a colorless neutral display in all azimuth angle directions, to a liquid crystal panel employing the optical film, and to a liquid crystal display apparatus employing the liquid crystal panel.
2. Description of the Related Art
FIG. 5A is a schematic sectional view of a typical conventional liquid crystal display apparatus, and FIG. 5B is a schematic sectional view of a liquid crystal cell to be used for the liquid crystal display apparatus. A liquid crystal display apparatus 900 is provided with: a liquid crystal cell 910; retardation plates 920 and 920′ arranged on both sides of the liquid crystal cell 910; and polarizing plates 930 and 930′ arranged on outer sides of the respective retardation plates 920 and 920′. Typically, the polarizing plates 930 and 930′ are arranged such that respective polarization axes are perpendicular to each other. The liquid crystal cell 910 includes: a pair of substrates 911 and 911′; and a liquid crystal layer 912 as a display medium arranged between the substrates. One substrate 911 is provided with: a switching element (typically, TFT) for controlling electrooptic properties of liquid crystals; and a scanning line for providing a gate signal to this switching element and a signal line for providing a source signal thereto (the element and the lines not shown). The other substrate 911′ is provided with: color layers 913R, 913G, and 913B forming a color filter; and a screen layer (black matrix layer) 914. A distance (cell gap) between the substrates 911 and 911′ is controlled by a spacer (not shown).
The retardation plates are used for optical compensation of the liquid crystal display apparatus. In order to obtain optimum optical compensation (improvement in viewing angle properties, color shift, and contrast, for example), various attempts have been made in optimization of optical properties of the retardation plates and/or arrangement of the retardation plates in the liquid crystal display apparatus. As shown in FIG. 5A, the retardation plates are conventionally each arranged between the liquid crystal cell 910, and the polarizing plates 930 or 930′ (see JP11-95208A, for example).
Further improvement in screen evenness and in display quality has been demanded for a recent high-resolution and high-performance liquid crystal display apparatus. However, the conventional liquid crystal display apparatus hardly develops a colorless neutral display in all azimuth angle directions. Further, with development of a small and portable liquid crystal display apparatus, a demand for reduction in thickness of the liquid crystal display apparatus has increased. | 2023-10-06T01:26:28.774034 | https://example.com/article/5360 |
Chromium plating is generally carried out in a plating bath containing hexavalent chromium. Recently, since hexavalent chromium has bad effects on the environment, etc., investigations about a trivalent chromium plating bath have proceeded. Chromium plating using a trivalent chromium bath has been proposed for a long time. Although chromium plating using a trivalent chromium plating bath has the feature that the plating adherence to a material is good without causing discoloration of the plated layer and without causing poor adherence of the plated layer to a material, unlike hexavalent chromium, the platable condition is limited. Thus, chromium plating of a material using a trivalent chromium plating bath has not yet been practically used.
A trivalent chromium plating bath has the problem that the stability of the plating liquid deteriorates when hexavalent chromium ions are formed by an anodic oxidation reaction, thereby decreasing the plating quality, etc. Thus, a chromium plating method is proposed wherein, by partitioning the plating bath into an anode chamber and a cathode chamber using an ion-exchange membrane, formation of hexavalent chromium ions is prevented.
In chromium plating, an inexpensive lead or lead alloy is generally used as the anode. However, where a lead-containing electrode is used, a sludge of the lead compound is formed which is difficult to treat, and the lead compound dissolved in the plating bath causes a reduction in the plating quality. Even where an ion-exchange membrane is used, the formation of hexavalent chromium can be avoided, but the formation of a lead compound sludge or dissolved lead compound cannot be prevented.
Thus, use of an electrode formed by coating a titanium substrate with platinum as the anode for chromium plating is described in JP-A-54-134038 (the term "JP-A" as used herein means an "unexamined published Japanese patent publication"), but the electrode does not have sufficient durability and the plating voltage increases in a relatively short period of time.
Also, for preventing the formation of hexavalent chromium at the anode, the use of an electrode comprising an alloy of iron or nickel and the oxide thereof as the anode is described in JP-B-56-43119 (the term :JP-B" as used herein means an "examined published Japanese patent publication"), and the use of a ferrite anode is described in JP-B-61-22037. However, when these electrodes are used as the anode, the formation of a sludge due to dissolution of the catalyst component which constitutes the electrode, reduction in the quality of the plated product by the adherence of the dissolved components on the surface of the plated product, or reduction in the plating efficiency is remarkable.
Also, JP-A-61-23783 and JP-A-61-26797 each describe that a plating bath is partitioned into an anode chamber and a cathode chamber using an ion-exchange membrane, an aqueous solution having dissolved therein a trivalent chromium salt is supplied to the cathode chamber, an acid solution of the same anion as that of the trivalent chromium salt is supplied to the anode chamber, an electrode comprising lead or titanium coated with a noble metal or a noble metal oxide is used as the anode where a sulfuric acid solution is used, and an electrode comprising a graphite or titanium coated with a noble metal or a noble metal oxide is used as the anode where a chloride solution is used. However, in these patent publications, only examples using a graphite electrode are described, and there are no descriptions of an electrode having a coating of a noble metal or a noble metal oxide. | 2024-02-03T01:26:28.774034 | https://example.com/article/7529 |
Human renal-cell carcinoma cells are able to activate natural killer cells.
We previously reported that natural killer (NK) cells that had infiltrated renal-cell carcinoma (RCC) proliferated vigorously in culture with interleukin-2 (IL-2) and lysed autologous tumor cells. In this study, we investigate the susceptibility of RCC cells to NK-cell lysis and their ability to stimulate proliferation and increase phenotypic expression and function of NK cells. Cells from primary culture of RCC (p-RCC cells) were significantly more susceptible to the lysis mediated by human NK3.3 clones than were cells from primary culture of metastatic melanomas. Both RCC-cell clones and cells from primary culture of non-tumorous kidneys were also susceptible to lysis by NK3.3 clones and IL-2-activated peripheral blood lymphocytes (PBLs). Incubation of NK3.3 clones with p-RCC cells in the absence of IL-2 induced proliferation of NK3.3 clones, whereas incubation with cells from primary culture of metastatic melanomas, K562 cells, or any others tested did not. The p-RCC cells from earlier passages were more potent inducers of NK-cell proliferation than were those from older passages. Cell-free culture supernatants of p-RCC cells with or without NK3.3 clones failed to induce NK-cell proliferation. Incubation of CD16+ NK cells purified from PBLs with p-RCC cells induced higher proliferation of the NK cells only in the presence of IL-2, whereas incubation with cells from primary culture of metastatic melanomas did not. Incubation of NK3.3 clones with p-RCC cells resulted in an increase in CD16, CD25 (IL-2 receptor-alpha), and HLA-DR antigen expression and cytotoxicity in NK3.3 clones. In summary, these results suggest that RCC cells are able to activate NK cells, potentially through cell-to-cell interaction. | 2024-06-28T01:26:28.774034 | https://example.com/article/1958 |
Louisiana lawmakers rejected a bill on Sunday that would have set a minimum age to marry and instead rewrote the measure to allow those under age 18 to wed with a parent's blessing.
The bill, introduced in March by Democratic state Sen. Yvonne Dorsey-Colomb, would bar anyone under age 16 from marrying in the state and block 16- and 17-year-olds from marrying anyone more than four years older.
When the House took up the bill, several conservative Republicans, whose party controls the chamber, balked at the idea, heavily rewriting the bill to allow those under 18 to marry with parental consent and requiring those under 16 to get judicial consent.
The rewritten version passed the House 66-28 on Sunday and now goes back to the Senate. The state's legislative session ends Thursday.
Some Republican lawmakers argued that allowing those under 18 to marry would be beneficial in cases of pregnancy and also touted the benefits of marriage.
“If they’re both 16 years old, and they both consent to sexual relations, and they’re about to have a baby, why wouldn’t we want them to be married?” state Rep. Nancy Landry, a Republican, said Sunday. “Just as a public policy of the state we want children born into wedlock, if possible.”
Supporters of a strict minimum age to marry called the bill a child protection measure, saying it would keep teenagers from marrying sexual predators and citing marriages of teenagers to people decades older.
Across the country, laws allowing minors to wed are common, NBC News previously reported. Louisiana is one of 15 states with no minimum marriage age, according to the Tahirih Justice Center, a nonprofit that seeks to protect women and girls from violence. And a majority of states allow 16- and 17-year-olds to marry, often with the consent of a parent or judge.
Nearly a quarter of a million children were married in the U.S. from 2000 to 2010, most of them girls marrying older men, according to the advocacy group Unchained at Last. Experts note that child marriage can have negative effects on young women, causing social, educational and economic strains over the course of their lives. | 2023-09-08T01:26:28.774034 | https://example.com/article/6505 |
27 F.3d 565
146 L.R.R.M. (BNA) 2704
NOTICE: Fourth Circuit I.O.P. 36.6 states that citation of unpublished dispositions is disfavored except for establishing res judicata, estoppel, or the law of the case and requires service of copies of cited unpublished dispositions of the Fourth Circuit.VIRGINIA MANUFACTURING COMPANY, INCORPORATED (VAMCO), Petitioner,NATIONAL LABOR RELATIONS BOARD, Respondent.NATIONAL LABOR RELATIONS BOARD, Petitioner,v.VIRGINIA MANUFACTURING COMPANY, INCORPORATED (VAMCO), Respondent.
Nos. 93-1824, 93-1955.
United States Court of Appeals, Fourth Circuit.
Argued April 11, 1994.Decided June 29, 1994.
On Petition for Review and Cross-Application for Enforcement of an Order of the National Labor Relations Board. (11-CA-14621-2, 11-CA-14621-3, 11-CA-14621-4, 11-CA-14621-5, 11-CA-14766)
Argued: Gary Williams Wright, Wimberly & Lawson, Knoxville, TN. On brief: Kevin M. Dorris, Wimberly & Lawson, Knoxville, TN, for petitioner.
Argued: Joseph Anthony Oertel, National Labor Relations Board, Washington, D.C. On Brief: Jerry M. Hunter, Gen. Counsel, Yvonne T. Dixon, Acting Deputy Gen. Counsel, Nicholas E. Karatinos, Acting Assoc. Gen. Counsel, Aileen A. Armstrong, Deputy Assoc. Gen. Counsel, Howard E. Perlstein, Supervisory Atty., National Labor Relations Board, Washington, D.C., for respondent.
1
N.L.R.B.
2
ENFORCEMENT GRANTED.
3
Before HALL and LUTTIG, Circuit Judges, and WARD, Senior United States District Judge for the Middle District of North Carolina, sitting by designation.
OPINION
PER CURIAM
4
Virginia Manufacturing Co. (VAMCO) petitions for review of an order of the National Labor Relations Board (NLRB) finding that VAMCO had violated Secs. 8(a)(1) and 8(a)(3) of the National Labor Relations Act (the Act).1 The NLRB cross-petitions for enforcement of its order. We deny the petition for review and grant enforcement of the order.
I.
5
VAMCO manufactures metal and wood cabinets and containers at a factory in Pennington Gap, Virginia. The company has around 120 employees, including supervisors and management.
6
On June 20, 1991, a group of employees decided to strike for improved working conditions. They went to each of the four buildings in the factory to drum up support. About twenty employees struck on the first day, but the number of strikers soon doubled. The strikers contacted the United Mine Workers to seek help in organizing. Enough authorization cards were collected to force a representation election, and one was scheduled for August 9, 1991.
7
With many employees still crossing the picket line, tempers flared. The company filed an unfair labor practice charge with NLRB Regional Counsel alleging that strikers had used threats and vandalism in order to coerce and intimidate non-striking employees. Thirty affidavits were filed in support of the charge.
8
NLRB Regional Counsel postponed the election. On the date the election would have been held--August 9, 1991--the striking employees made an unconditional offer to return to work.
9
On the following Monday, August 12, the forty or so striking employees reported for work. At the direction of company supervisors, they gathered in a small break room. Charlie Fugate, VAMCO's Executive Vice President, addressed the assembly of returning strikers. He explained that, because of the strike, there were not enough materials on hand to immediately resume full production. He said that eight employees could work that day, and that the rest would be called back as production increased. The employees for whom work was not available peacefully left the premises and set up an "informational" picket line that no longer interfered with non-striking employees.
10
On August 30, 1991, NLRB Regional Counsel advised both VAMCO and the union that it planned to file unfair labor practice charges against the union.2 The union agreed to settle the charges, and, though the compliance period had to be extended once, the charges were settled.
11
In any event, on September 4, 1991, perhaps buoyed by the NLRB's decision to charge the union, VAMCO took the step that led to this case--it fired five employees because of alleged misconduct during the strike. The employees filed unfair labor practice charges on account of their terminations, and the union supplemented the charge with a couple of incidents of alleged company coercion that had occurred at the outset of the strike.
12
After a five-day hearing before an administrative law judge (ALJ), the company was found to have violated Sec. 8(a)(1)3 by discharging four (Birman, Duncan, Crusenberry, and Woodard) of the five employees and by threatening to discipline employees who joined the strike. The ALJ found no violation, though, in an incident in which the plant superintendant warned Birman as he left to join the strike, "Steve, it's your job."
13
The ALJ ordered VAMCO to cease and desist from the violations, to reinstate the four workers with back pay, and to post a remedial notice to employees.
14
Both sides filed exceptions to the ALJ's decision. The NLRB affirmed the violations found by the ALJ and, unlike the ALJ, found that Hurd's comment to Birman also violated Sec. 8(a)(1). The NLRB also cited Sec. 8(a)(3)4 in support of its finding that the firing of the four employees was illegal.
15
VAMCO petitions for review under 29 U.S.C. Sec. 160(f); the NLRB petitions for enforcement under 29 U.S.C. Sec. 160(e). Where the NLRB's findings of fact are supported by substantial evidence on the record as a whole, they are "conclusive." Universal Camera Corp. v. NLRB, 340 U.S. 474, 493 (1951).
II.
16
A striking employee remains an "employee" under the Act, 29 U.S.C. Sec. 152(3), and he may not generally be fired or refused reinstatement at the conclusion of the strike. NLRB v. Fleetwood Trailer Co., 389 U.S. 375, 378 (1967).5 On the other hand, employee discipline that neither coerces nor discriminates on account of activity protected by the Act does not implicate the Act. NLRB v. Fansteel Metallurgical Corp., 306 U.S. 240, 254 (1939). Because serious misconduct by strikers is not protected by the Act, discipline, including refusal to reinstate the guilty employee, for such misconduct does not violate Sec. 8(a)(1) or 8(a)(3). Paramont Mining Corp. v. NLRB, 631 F.2d 346, 349 (4th Cir.1980); NLRB v. Pepsi Cola Co. of Lumberton, Inc., 496 F.2d 226, 228 (4th Cir.1974); Oneita Knitting Mills, Inc. v. NLRB, 375 F.2d 385, 390 (4th Cir.1967). On the other hand, where an employer condones strike misconduct and reinstates the offending striker, the employer may not thereafter rely on the misconduct to discharge the employee. NLRB v. Community Motor Bus, 439 F.2d 965, 967-968 (4th Cir.1971).
17
VAMCO alleges that Birman, Duncan, Crusenberry, and Woodard engaged in serious strike misconduct.6 The ALJ did not decide whether the misconduct charges were true, because he found (and the NLRB agreed) that VAMCO had condoned any misconduct when Fugate told all strikers that they would be reinstated as production increased.
18
This finding is supported by substantial evidence. The classic definition of condonation was provided by the Seventh Circuit in Jones & McKnight, Inc. v. NLRB, 445 F.2d 97, 103 (7th Cir.1971):
19
The key element of condonation is a clearly evidenced intention and commitment on the part of the employer to overlook the misconduct and to permit a continuation or resumption as though no misconduct had occurred.
20
VAMCO argues that, when Fugate stated that all strikers would be called back, he was not forgiving strike misconduct, but instead was simply trying to calm a potentially volatile situation. Fugate's own testimony refutes the company's argument. Fugate acknowledged in his testimony before the ALJ that he intended, when he gave his speech to the strikers, to recall all of them.7 Moreover, he also agreed that his subsequent decision to fire Duncan, Birman, Crusenberry, and Woodard was a "change of heart." The doctrine of condonation protects employees from such "changes of heart":
21
The doctrine prohibits an employer from misleadingly agreeing to return its employees to work and then taking disciplinary action for something apparently forgiven.
22
Packers Hide Ass'n v. NLRB, 360 F.2d 59, 62 (8th Cir.1966).
23
Substantial evidence supports the NLRB's finding that Fugate unconditionally reinstated the four employees notwithstanding his belief that they had engaged in strike misconduct. The slate was wiped clean, misconduct forgiven, and the employment relationship unconditionally renewed.8 The order resulting from the NLRB's conclusion that VAMCO violated Secs. 8(a)(1) and (3) by later firing the employees is therefore enforced.
III.
A.
24
On the day the strike began, plant superintendent Hurd spoke to about a dozen assembled workers. He told them that anyone who did not report to work the following day would be given an unexcused absence.9 Company policy at the time was that an employee who had three or four unexcused absences could be fired. The ALJ and NLRB both found that Hurd's statement constituted a threat of reprisal for engaging in activity protected by Sec. 7 of the Act, in violation of Sec. 8(a)(1). See NLRB v. Nueva Engineering, Inc., 761 F.2d 961, 966 (4th Cir.1985). This finding is clearly supported by substantial evidence, and it is therefore enforced.
B.
25
Earlier that same day, Hurd asked Birman what he was going to do. Birman said he thought he would join the strike, and he tried to explain the strikers' demands for better working conditions. Hurd shrugged his shoulders and cut off Birman's explanation. Hurd said, "Steve, it's your job."
26
The ALJ held that this statement did not violate Sec. 8(a)(1) because it was made before Hurd knew that the workers were engaging in conduct protected by Sec. 7. The NLRB reversed this finding,10 and with good reason. Hurd knew that a concerted work stoppage was underway, and he surely suspected its aim was to improve employment conditions in some fashion. Birman even tried to explain the nature of the strike, and Hurd declined to hear about it. Substantial evidence supports the NLRB's finding, and it is enforced.
27
In sum, VAMCO's petition for review is denied, and the order of the NLRB is enforced in its entirety.
28
PETITION FOR REVIEW DENIED; ENFORCEMENT GRANTED
29
LUTTIG, Circuit Judge, concurring in part and dissenting in part:
30
I join in Part III of the majority's opinion, but dissent from Part II because this court's decision in N.L.R.B. v. Community Motor Bus, 439 F.2d 965, 967 (4th Cir.1971), squarely controls our disposition of the condonation issue and requires us to hold that VAMCO did not condone any of its employees' strike misconduct.
31
In Community Motor Bus, following illegal picketing, the union officials specifically asked management whether the strikers were fired. The employer's superintendent responded by reassuring the union officials that "[the strikers] were not fired, that the company wanted all the strikers back," and that he "hope[d] that all the strikers would return...." Id. Reversing the Board's finding of condonation, we held that not even these statements "established a clear showing of an attitude of forgiveness and a willingness to 'wipe the slate clean.' " Id. at 967-68 (citations omitted); accord, e.g., Jones & McKnight, Inc. v. N.L.R.B., 445 F.2d 97, 103 (7th Cir.1971) ("Condonation can be found and is invocable only where there is clear and convincing evidence that the employer has completely forgiven the guilty employee for his misconduct ....") (quoting Packers Hide Association v. N.L.R.B., 360 F.2 59, 62 (8th Cir.1966). If the statements made by management in Community Motor Bus were insufficient to establish condonation, a fortiori the statements made in this case do not establish condonation. Here, management was not responding to a direct question as to whether the union employees were being fired; nor did it express any "hope" that the employees would return, much less state that it "wanted" them to return. Indeed, the only relevant testimony in the record is that the management representative who made the one statement that workers would be rehired believed at the time that the company was legally required to rehire the strikers, a belief that belies any suggestion of condonation.
32
We are, as a matter of court rule, and out of respect for principles of stare decisis, bound by our prior precedents. If there be a case the disposition of which is dictated by a prior decision, then it is this by Community Motor Bus. The majority most assuredly recognizes as much, as evidenced by its transparent effort at distinction. Not only in this case was there no "fully consummated renewal of the employment relationship," see ante at 7 n. 8; standing alone, whether there was or not is irrelevant (and was viewed as irrelevant by the court in Community Motor Bus ) to whether there was management condonation of the workers' prior conduct. Were it otherwise, there would, as a matter of law, be condonation of prior conduct in every instance where employees are rehired, regardless of the evidence of affirmative disapproval.
33
Because Community Motor Bus directly controls this case, and because this panel lacks the authority to decide this case in a way that contravenes our prior precedent, I respectfully dissent.
1
29 U.S.C. Sec. 151 et seq
2
See Sec. 8(b)(1)(A) of the Act, 29 U.S.C. Sec. 158(b)(1)(A), which prohibits labor organizations from restraining or coercing employees in the exercise of the employees' Sec. 7 rights ("to self-organization, to form, join, or assist labor organizations, to bargain collectively through representatives of their own choosing, and to engage in other concerted activities for the purpose of collective bargaining or other mutual aid or protection, and ... to refrain from any or all of such activities except to the extent that [a collective bargaining agreement may require membership in a union]")
3
29 U.S.C. Sec. 158(a)(1), prohibiting employer interference, restraint, or coercion of employees in the exercise of their Sec. 7 rights
4
29 U.S.C. Sec. 158(a)(3), prohibiting "discrimination in regard to hire or tenure of employment ... to discourage membership in any labor organization."
5
An economic striker's position may be filled during the strike by a temporary or permanent replacement. If the hiring of permanent replacements leaves fewer jobs vacant at the end of the strike than there are strikers seeking reinstatement, the employer need reinstate only as many strikers as there are available positions, so long as it does not discriminate among the returning strikers on account of the fervor of their union sentiments. NLRB v. Mackay Radio & Telegraph Co., 304 U.S. 333, 346 (1938)
6
The misconduct involved rock throwing, threats of physical harm, and attempted vandalism with "jack rocks."
7
Fugate admitted that he did not know that he could legally fire any of the strikers when he gave his speech. Though VAMCO argues that this testimony shows that Fugate did not intend to waive the company's right to fire for misconduct, we agree with the NLRB that it shows just as clearly that Fugate intended to reinstate everyone without reservation
8
The fully consummated renewal of the employment relationship distinguishes this case from Community Motor Bus, 439 F.2d 965, 967-968, where we held that an employer's statement during the strike that it "wanted" all of its striking employees to come back fell short of "an unequivocal invitation to the strikers to return to work regardless of their misconduct." We also pointed out that, even if we assumed that the statement was such an invitation, the strikers had rejected it by remaining on strike
9
The absentee calendars for Duncan, Birman, Crusenberry and Woodard were in fact marked "unexcused" during the strike
10
The NLRB's disagreement with the ALJ does not change the standard for our review, because the NLRB's disagreement did not arise within the one area--credibility of witnesses--in which it owes the ALJ's finding particular deference. NLRB v. Frigid Storage, Inc., 934 F.2d 506, 509 (4th Cir.1991); American Thread Co. v. NLRB, 631 F.2d 316, 320 (4th Cir.1980)
| 2024-06-27T01:26:28.774034 | https://example.com/article/9819 |
Chapter 108: Tomato Soup
After their training session, Raven and Javelin made their way back through the almost tunnel-like corridors, heading for their dorm rooms in the so-called Water Dome. All of it might sound dark and damp, but the white stone that the corridors were walled with had a soft, self-glowing luminescence to it, filling the entire underwater academy with a soft light. As for the Water Dome, it was actually quite spectacular.
However, no matter how bright or impressive the academy’s construction was, Hoatzin had grown too accustomed to the open skies. He had only come to see his sister and had left for the surface as soon as that was done.
As Raven and Javelin headed for their rooms, the duo met several Sea Academy students, all of whom eyed Raven with fear-touched delight, kind of like when one comes really close to a lion at a zoo. There was some jealousy too, naturally, but a lot less than Raven had expected. Even without her parading around her age and presumed peak Adept cultivation, word had still gotten out and once the rumors were proven true, she became the center of everyone’s conversations.
Javelin, on the other hand, received significantly cooler looks; respectful, yet clearly antagonizing. Raven guessed that while her accomplishments were extraordinary enough to shatter all notions of rivalry, Javelin’s weren’t; they were undoubtedly impressive, but not entirely unachievable.
“Incoming,” Raven warned just before a tall beauty walked out into the corridor leading to the advanced students’ dorm.
“Senior Graduate Tanuki,” both Raven and Javelin greeted, so in sync that their somewhat insubordinate greeting seemed completely innocent.
“We meet again,” Javelin continued before Canis had a chance to react and was then quickly followed by Raven, the pair of them sinking into private conversation. “That’s twice today now – how auspicious,” she said with a smile before leaning her head to the side. “. . . And how odd.”
“Odd?” Javelin asked, still giving no opportunity for Canis to get a word in.
“Well, aren’t graduates supposed to live off-campus during the months between their graduation and the tournament?”
“Oh, you’re right, Raven; it is rather rare,” Javelin replied, his voice now loud enough for the few nearby students to hear him. “One might think that she’s using the tournament as an excuse to milk resources from the Academy. . . .”
A cold, murderous glint flashed by in the depths of Canis’ eyes, but she too faked laughter. “Indeed, preposterous. . . .”
“How fortunate then that we all know better.” Raven leaned in closer to Javelin, locking her arm with his.
The corner of Canis’ eyes twitched slightly at the sight of their linked arms, but Raven had to admit that this girl was better at hiding her emotions than Javelin’s sister was. Although that might say more about Remora than it did about Canis.
“It is getting late; children should go to bed,” said the tall girl before she moved to pass by them, yet Canis still paused briefly at Raven’s side. “Sweet dreams, child.”
The corners of Raven’s lips twisted into a lopsided smirk as she watched Canis leave. ‘Is the girl losing her patience, perhaps?’ Raven mused to herself before she and Javelin resumed the journey towards their dorms.
Even tethered to Javelin’s side, Raven had long since figured out that Canis had returned for the tournament to find out what happened to her brother. Ever since her arrival, well-hidden presences had been following Raven and Javelin everywhere, watching silently from afar.
While they couldn’t be considered the talkative types, Raven had still overheard enough of their conversations to know what they were looking for; evidence of her and Javelin’s involvement in Jack’s mental breakdown. However, since Raven had made sure that there was no such evidence, she figured it was only a matter of time until they tried something more drastic.
Raven and Javelin kept walking deeper into the network of softly glowing, white tunnels and it didn’t take long before they reached a wide double door. In front of it sat two white-haired men, with very different appearances. One was old and shriveled up, while the other was significantly younger, despite his hair.
“Lady Nightingale,” the younger of the two stood and greeted Raven with a warm smile.
The two men the turned to glare angrily at each other, clearly not agreeing on the other’s choice of greeting.
“Protector Aves, Protector Elas,” Raven and Javelin returned the greetings as they passed between the two men, completely ignoring the tension in the air. Elas was the Sea Academy’s equivalent to Aves and now that Aves needed to keep an eye on Raven, Headmaster Hammer had suggested the pair of them should work together. Needless to say, they didn’t get along.
Once through the double doors, a huge, nearly transparent dome spread out around them. This was the Water Dome. It was so large that several buildings could fit underneath it, all of which were large enough to house dozens of people. During the day, the slightly frosted dome allowed water-filtered light to shine through, causing glitter patterns to dance over the ground and houses. Every now and then, large sea creatures would swim by, casting impressive shadows.
Here, the air was thick with natural spirit essence, sucked in from the sea through the seemingly thin crystalline walls. This was where the advanced students and the Academy’s Elders resided.
Together, Raven and Javelin headed for one of the smaller houses, located a bit to the side, isolated from the rest. This building was only large enough for four mid-sized rooms, separated by a common courtyard in the middle.
The two of them entered the courtyard and Raven swiftly walked up to the rightmost door. With only a slight glance in Javelin’s direction, she slipped inside. Still outside, Javelin paused for a second. He then sighed before silently pushing open the door just to the left of the one Raven had used.
Perhaps not surprisingly, Javelin had been very opposed to the notion of separate rooms. However, unfortunately for him, the few months since becoming Soul Bound had been enough to increase the distance he and Raven could manage between them by quite a bit. By now it spanned just over two hundred meters; it wasn’t a lot in the grand scheme of things, but it was enough for them to have separate rooms – something Javelin’s mother insisted on. He had, however, relented a bit when he realized that they had been given this four-room house for themselves; at least he didn’t have to worry about someone else drooling over Raven.
In her room, Raven strode over to her bed and sat down on it with her legs crossed. Closing her eyes, Raven expanded her other senses and let her hundreds of spirit connections swarm her with information. As if expanding her body, Raven could feel every single movement within a four-hundred-meter radius like a prickle on her skin.
A cold and somewhat savage smile spread on her lips; the drastic measures had finally begun.
In the adjacent room, Javelin had also headed for his bed when he entered, only he wasn’t quite as graceful; he flopped down on it, face down, as soon as it was withing reach. Every muscle in his body ached to the point where Javelin was impressed that he even managed to make it back to the room without collapsing.
Raven had told him to meditate for a while and think over the day’s training, but no sooner had Javelin’s head hit the pillow than he fell asleep. Even the sudden increase in killing intent he received from Raven’s soul prism couldn’t keep him awake.
With a start, Eric stirred from his sleep. His face felt sore and his back stiff; drowsily stretching, he realized that he had fallen asleep at his desk again. Feeling his face, Eric groaned as he felt the grooves left by his keyboard.
Eric glanced at the holographic screen in front of him. It was three o’clock in the morning. Great.
Yawning, he pushed away from his desk and got up to leave his office. In his sluggish state, Eric almost forgot to lock up after himself, but he remembered in the last second and pulled out his keychain. Looking down at the oddly old-fashioned keys, Eric found himself smiling; a photo of his parents dangled among them. He wasn’t really one for photos – especially not the on-paper kind – but his mother had insisted; said it was a good luck charm, or something. As if a piece of glass-encased paper could possibly affect the happenings in the universe.
A sudden crash, far behind him, drew Eric’s attention away from the photo on his keychain. He turned to face the direction of the noise, but when no new sounds came, Eric shrugged it all off as a fragment of his imagination – brought on by sleep deprivation, no doubt.
He finished locking up and headed down the clinically white tunnels towards his bedroom. Even though the base was buried in tens-of-meters-deep snow this time of year, the strong arctic winds blowing outside could still be heard. The rhythmic sounds were oddly akin to raging ocean waves and were very soothing.
Just as Eric was about to enter his room, a grumble in his stomach reminded him that he hadn’t eaten since lunch the day before. Usually he wouldn’t care – a quick nibble of a supplement bar and he’d be fine – but ever since his new bodyguard had arrived, her constant nagging about eating right had practically brainwashed him.
Eric turned and headed for the kitchen. It wasn’t far – only two doors further down the corridor. He reached out his hand to open the door, but before he could pull the handle, the thing swung open and Miss Night stepped out.
“Professor Solar, still stuck to your computer, I take it?” she said with a slight smirk as she looked pointedly at Eric’s chin. Her little play at words almost distracted him enough to not notice the two legs sprawled over the floor inside the kitchen, before the door blocked Eric’s line of sight.
A metallic tang filled the air and Eric looked down to see red stains on Miss Night’s fluffy indoor slippers with cat ears. They were the pair his assistant had forgotten before she left on maternity leave, and the only pair small enough for his bodyguard’s petite feet, but now they looked oddly macabre.
“We spilled tomorrow’s tomato soup,” Miss Night explained when she noticed Eric’s stare. She said it so nonchalantly that he almost believed her – almost.
A loud crash snapped Javelin awake. He sprung up from his bed and looked over at his dorm room door, only to see Raven swiftly closing it behind her.
“Sorry to wake you, Jav; I thought you would still be meditating on today’s training. . . .” Raven’s tone was playful and teasing, but Javelin just glanced down at her feet, ignoring her remark.
“No tomato soup tomorrow then?” he asked, but he barely noticed Raven’s body stiffen; he was too distracted by the sudden stabbing pain in his mind and the blackening world around him.
Like this:
14 thoughts on “Chapter 108: Tomato Soup”
I don’t understood what is there to discover, couldn’t Raven revealed what relay happened to at least higher ups from all empires, and since Tanuki was working with Talons to kill Raven and Javelin then even if he was dead Earth empire shouldn’t have any claims tu punish Raven since it was Tanuki own fault.
(sorry for using last names, I forgot first names)
It doesn’t work that way. Even if it was Tanukis fault, as you have seen, Elder Tanuki wants revenge, and he’s the type who will stop at nothing to get it. His own emperor dropping the investigation wasn’t enough for him to back off.
Raven has a very tight control on information. The more you keep your enemies guessing, the less power they have.
and left for the → and had left for the (just to have the same tense)
than Javelin’s sister was. → than Javelin’s sister. (no mistake, just a doubling)
briefly by Raven side → briefly by Raven’s side (I would use “at” instead of “by” as well)
was no such evidence → was no such evidence
the others choice of greeting → the other’s choice of greeting
all of with large enough → all of which were large enough
dancing glitter patters over the → dancing glitter patterns on the (Did I get that right?)
He had however relented → He had, however, relented (you usually do that if I’m correct)
within a four hundred radius → within a four hundred meter radius
that he fallen asleep → that he had fallen asleep
sees me like this she’s going → sees me like this, she’s going
of the noise but when → of the noise, but when
tens-of-meter-deep snow → tens-of-meters-deep snow
open the door but before he → open the door, but before he | 2024-07-01T01:26:28.774034 | https://example.com/article/1634 |
Q:
how to parse json with various arrays
I have a json file that looks like:
[
{
"id": "aaa",
"idMembers": [
"David",
"Mary"
],
"actions": [
{
"id": "1",
"date": "2019-08-28"
},
{
"id": "2",
"date": "2019-08-29"
},
{
"id": "3",
"date": "2019-08-30"
}
]
},
{
"id": "bbb",
"idMembers": [
"Mar",
"Alex"
],
"actions": [
{
"id": "1",
"date": "2019-07-28"
},
{
"id": "2",
"date": "2019-07-29"
}
]
}
]
I would like to obtain a result like:
["David", "Mary", "1", "2019-08-28"]
["David", "Mary", "2", "2019-08-29"]
["David", "Mary", "3", "2019-08-30"]
["Mar", "Alex", "1", "2019-07-28"]
["Mar", "Alex", "2", "2019-07-29"]
I tried:
jq -c '.[] | [ .idMembers[], .actions[].id, .actions[].date] '
But results are:
["David", "Mary", "1", "2", "3", "2019-08-28", "2019-08-29", "2019-08-30"]
["Mar", "Alex", "1", "2", "2019-07-28", "2019-07-29"]
I would like do someting like:
jq -c '.[] | .idMembers[], .actions[] | [ .id, .date] '
but it return me
jq: error (at :1268): Cannot index string with string "id"
Is possible to do something similar to this?
jq -c '.[] | .actions[] | [.idMembers[], .id, .date] '
A:
Make an array out of each object under actions and add it to idMembers.
.[] | .idMembers + (.actions[] | map(.))
map(.) can also be written as [.[]]. For clarification, above is the same as:
.[] | .idMembers + (.actions[0] | map(.)),
.idMembers + (.actions[1] | map(.)),
.idMembers + (.actions[2] | map(.)),
...
.idMembers + (.actions[n] | map(.))
where n is the number of elements in actions.
| 2024-04-10T01:26:28.774034 | https://example.com/article/9785 |
Cavaliers will win the series!
Am I the only one who thinks Lebron will somehow find a way to win this series. For some reason I just dont think Orlando will finish them off either that or I aint given D12 and hus boys enough credit
Orlando has outplayed them every game. What makes you think Cleveland can beat them three times in a row? Orlando should've swept them already. Cleveland doesn't match up, ESPECIALLY at the four spot & it has put them in panic mode. They've completely abandoned the style of play that got them here. Their bench has disappeared. As much as I like LeBron, I think it's funny that they're in this situation because they've been overconfident. All that pre & post game (even halftime) celebrating. Mo Williams guaranteeing a victory when he's played poorly the whole series. Overconfident.
Lebron needs another player. This offseason there are a few FA to be and the Cavs need to sign at least one of these guys. Turkoglu, Kleiza, BirdMan, Gortat, Odom. If they even got a Kleiza and Gortat I think this team would be the champs next year but I bet the Cavs eat their money this offseason in order to offer max to Bron, but this will make the Cavs the same team they have this year - Big Z unless he's resigned (personally I'd rathwer have Birdman or Gortat). Am I the only One Who thinks Gortat can be a top 10 center next season of recieving starter minutes?
Gortat isnt a good enough offensive player (or defender really) to be a top 10 center in the NBA. He is a backup player. But I dont think the Cavs will come back, they should be home now. Orlando has taken every1 overlooking them personally and I dont see the Cavs beating them. I think the series ends tonight
I wouldn't say Orlando has dominated this series and I dont' know why the analysts see it that way. I think Orlando has been the better team, but not anything near domination. Game 1,2,4 were decided by a total of 4 points! Somehow Turkoglu's tough fadeaway with 1 second is forgotten, after james's the shot. Rashard Lewis hit 2 fadeaway 3 with less than seconds. Orlando does get respect for the game 3 which was dominating, but really this series has been pretty even. | 2023-09-18T01:26:28.774034 | https://example.com/article/8711 |
Systematic analysis of proteins from different signaling pathways in the tumor center and the invasive front of colorectal cancer.
In colorectal cancer, the functional impact of proteins from different signaling pathways varies between tumor center and tumor front. Our objective was to identify differential protein expression profiles between the tumor center and the tumor front of colorectal cancer. Twenty proteins from different signaling pathways (epidermal growth factor receptor [EGFR], phosphorylated extracellular signal regulated kinase [pERK], receptor for hyalouronic acid mediated motility [RHAMM], Raf-1 kinase inhibitor protein [RKIP], β-catenin, E-cadherin, phosphorylated AK transforming [pAKT], p16, p21, Ki-67, B-cell Lymphoma-2 [BCL2], vascular endothelial growth factor, apoptosis protease activating factor 1 [APAF-1], mucin1 [MUC1], ephrin B2 receptor [EphB2], matrix metalloproteinase 7 [MMP7], phosphorylated mothers against decapentaplegic 2 [pSMAD2], caudal type homeobox transcription factor 2 [CDX2], Laminin5γ2, and mammalian sterile 20-like kinase 1 [MST1]) involved in colorectal cancer progression were studied immunohistochemically on 220 well-characterized patients using a multiple-punch tissue microarray including 437 and 430 samples from the tumor center and the invasive front, respectively. Mean expression between the tumor center and the tumor front varied statistically significantly for pSMAD2, pERK, Raf-1 kinase inhibitor protein, E-cadherin, pAKT, BCL2, vascular endothelial growth factor, EphB2, matrix metalloproteinase 7, CDX2, Laminin5γ2, MST1, and APAF-1. Overexpression of pAKT, BCL2, vascular endothelial growth factor, APAF-1, pERK, EphB2, Raf-1 kinase inhibitor protein, CDX2, E-cadherin, MST1 (P < .001 each), and pSMAD2 (P = .002) was more frequently observed in the tumor center, whereas matrix metalloproteinase 7 and Laminin5γ2 (P < .001 each) overexpression was associated with the invasive front. In multivariate analysis, vascular endothelial growth factor (P < .001), Raf-1 kinase inhibitor protein (P = .009), and Laminin5γ2 (P < .001) were the most relevant proteins with the multimarker phenotypes positive/positive/negative and negative/negative/positive being most discriminating between the tumor center and the tumor front. Moreover, the combination negative/negative/positive vascular endothelial growth factor/Raf-1 kinase inhibitor protein/Laminin5γ2 at the tumor front was associated with vascular/lymphatic invasion (P = .014), distant metastasis (P = .019), higher tumor grade (P < .001), and poorer survival (P = .05). Our findings show that, in colorectal cancer progression, vascular endothelial growth factor overexpression seems to play a role in the tumor center, whereas Laminin5γ2-positivity combined with Raf-1 kinase inhibitor protein loss is associated with tumor invasion at the front. | 2024-02-05T01:26:28.774034 | https://example.com/article/3882 |
Blockchain Platform Backed by Oil and Banking Giants Goes Live
UK-based blockchain venture VAKT launched its commodity trading platform this Wednesday, shareholder Gunvor Group told Reuters. Currently, the platform focuses on oil trading, allowing companies that physically trade BFOET crude oil to streamline processes and benefit from improved security. VAKT is claimed to be the world’s first blockchain-based commodity trading platform that is fully operational and aimed at enterprises.
In November 2017, we reported that VAKT had been launched by a group of banking giants, oil companies, and commodity trading firms, including British Petroleum ( BP (LON:BP)), Equinor,…
This article appeared first on Cryptovest
Like this: Like Loading... | 2024-01-07T01:26:28.774034 | https://example.com/article/1195 |
Q:
Slider with jQuery using bullets
I have a slider with 3 images and left/right arrows. If you click on them, the image changes. You also have 3 bullets below the images and the image changes depending on what bullet you click.
I don't want to use buttons "arrows"; I want to use the tag "a." Any ideas on making it better? You'll need to add 3 images "because sliders use 3 images"
and the other 2 images are to use left/right arrows (to change the images). That is what I don't want to use, as I said.
HTML:
<!DOCTYPE html>
<html>
<head>
<title>Slider</title>
<meta charset="utf-8" />
<link rel="stylesheet" href="style.css">
<script src="js/jquery-2.1.4.min.js"></script>
<script src="js/slider.js"></script>
</head>
<body>
<div class="sliders">
<ul >
<li class="activa"><img src="fotos-de-Hamburguesa-americana.jpg"></li>
<li><img src="images (3).jpg"></li>
<li><img src="images21312.jpg"></li>
</ul>
<!-- <ul class="controles">
<li class="activa"> </li>
<li> </li>
<li> </li>
</ul> -->
</div>
<div class="sliders">
<ul>
<li class="activa"><img src="fotos-de-Hamburguesa-americana.jpg"></li>
<li><img src="images (3).jpg"></li>
<!-- <li><img src="images21312.jpg"></li> -->
</ul>
</div>
</body>
</html>
JS:
$.fn.slider = function(config){
var nodos = this;
var delay = (typeof config.delay == "number")?parseInt(config.delay):4000;
for (var i = 0; i < nodos.length; i++) {
Slider(nodos[i]);
}
function Slider(nodo){
var galeria = $(nodo).find('ul');
var btn1 = "<button class='before'></button>";
if(!$(nodo).hasClass('slider'))
$(nodo).addClass('slider');
if(!galeria.hasClass('galeria'))
galeria.addClass("galeria");
//Encontrar cuantas imagenes hay en la galeria
var imagenes = $(galeria).find('li');
//Controles
var html_bullets="<ul class='controles'>";
for (var it = 0; it < imagenes.length; it++) {
if(it==0)
html_bullets+="<li data-index='"+it+"' class='activa'> </li>";
else
html_bullets+="<li data-index='"+it+"'> </li>";
}
html_bullets+="</ul><button class='next'></button>";
$(nodo).append(html_bullets);
$(nodo).prepend(btn1);
var bullets = $(nodo).find("ul.controles li");
bullets.click(function(){
var index= $(this).data("index");
bullets.removeClass('activa');
imagenes.removeClass('activa');
$(imagenes[index]).addClass("activa");
$(bullets[index]).addClass("activa");
});
}
$(".slider").on("click","button.before",function(){
var div = this;
div = $(div).parent();
console.log(div);
flechas({div:div});
});
$(".slider").on("click","button.next",function(){
var div = this;
div = $(div).parent();
flechas({div:div,direccion:1});
});
function flechas(tipo){
var div = tipo.div;
var imagen = $(div).find("ul.galeria li.activa");
var imagenes = $(div).find("ul.galeria li");
var bullet = $(div).find("ul.controles li.activa");
var bullets = $(div).find("ul.controles li");
var index = bullet.data("index");
var max = bullets.length-1;
bullets.removeClass('activa');
imagenes.removeClass('activa');
if(tipo.direccion){
if(index == max){
$(imagenes[0]).addClass("activa");
$(bullets[0]).addClass("activa");
}else {
$(imagenes[index+1]).addClass("activa");
$(bullets[index+1]).addClass("activa");
}
}
else{
if(index == 0){
$(imagenes[max]).addClass("activa");
$(bullets[max]).addClass("activa");
}else {
$(imagenes[index-1]).addClass("activa");
$(bullets[index-1]).addClass("activa");
}
}
}
};
$(document).ready(function() {
$(".sliders").slider({delay:5000});
});
CSS:
.slider{
width: 420px;
overflow: hidden;
}
.slider ul{
list-style: none;
padding: 0;
}
.slider ul.galeria{
height: 200px;
position: relative;
margin-left: 30px;
}
.slider ul.galeria li{
position: absolute;
top: 0;
left: 0;
opacity: 0;
transition: all 2s;
}
.slider ul.galeria li.activa{
opacity: 1;
}
.slider ul.galeria img{
max-height: 200px;
margin-left: 5px;
}
/*Controles*/
.slider ul.controles {
text-align: center;
}
.slider ul.controles li{
background-color: black ;
display: inline-block;
width: 20px;
height: 20px;
border-radius: 10px;
}
.slider ul.controles li.activa{
background-color: blue ;
}
/*Botones-flechas*/
.slider button.before{
background-image: url(Flecha_002.png);
position: relative;
left: 0;
top: 128px;
background-repeat: no-repeat;
background-size: 28px;
height: 48px;
width: 33px;
background-color: white;
border: none;
}
.slider button.next{
background-image: url(Flecha_001.png);
position: relative;
left: 86%;
bottom: 190px;
background-repeat: no-repeat;
background-size: 28px;
height: 48px;
width: 33px;
background-color: white;
border: none;
}
.slider button.before:focus{
outline: none;
}
.slider button.next:focus{
outline: none;
}
.slider button.before:hover,.slider button.next:hover,.slider ul.controles li:hover{
cursor: pointer;
}
A:
Your code is good, but there's some points you can improve upon:
Assumptions:
$.fn.slider = function(config){
var nodos = this;
var delay = (typeof config.delay == "number")?parseInt(config.delay):4000;
You're assuming config won't be empty or not added. You should have a default config, and simply extend the parameter config to include the items the parameter config left off.
abusing jQuery:
You may not need to use jQuery for everything: See youmightnotneedjquery.com for a full list.
For example:
$(nodo).find('ul') can be written as nodo.getElementsByTagName('ul')
$(this).data("index") can be written as this.getAttribute('index')
$(div).parent() can be written as div.parentElement
.addClass can be written as .classList.add
Better call the redundancy department department:
Your code has quite a bit of redundancy, for example:
var div = this;
div = $(div).parent();
console.log(div);
flechas({div:div});
Could be expressed as:
flechas({div: this.parentElement});
And the following is also redundant:
var btn1 = "<button class='before'></button>";
var html_bullets="<ul class='controles'>";
html_bullets+="...";
$(nodo).append(html_bullets);
$(nodo).prepend(btn1);
Simply remove btn1 and attach its contents to html_bullets.
Indentation and spacing:
Your indentation and spacing is wrong:
You should have spaces around your operators and after commas.
You should have each layer of indentation indented by either two, four or eight spaces. Additionally, keep consistent.
Miscellanous
typeof vs. instanceof: While both are similar, I would prefer to use instanceof as it lets you declare the type as the type, meaning the compiler will pick up if you mess up the format on the name:
if (config.delay instanceof Number)
parseInt(config.delay): there's many ways to do this as described by this example, however, I would prefer Number(config.delay) as it looks more clear as to what are trying to create.
In addition to this above point, leaving off the second parameter in parseInt can cause strange issues. Unless needed, you can use 10 as the second parameter to parse to decimal.
| 2024-05-16T01:26:28.774034 | https://example.com/article/3503 |
'Communists of Russia' urge massive nationalization, return of death penalty in elections program
A minor but media savvy political party, Communists of Russia, has released a populist elections program. Its proposals feature a call to bring back the death penalty, nationalization of major companies, and to restore the status quo of the USSR.
The party leader Maksim Suraikin told reporters the title of their plan was “Ten Stalinist Blows to Capitalism”. It includes the intention to introduce a constitutional ban on raising the retirement age, limit food prices and at the same time increase average salaries and pensions in the country. Another “Stalinist blow” is opposition to any attempts of imposing religious ideas on society.
Suraikin also said he would personally head the party’s elections list and promised that Communists of Russia wouldn’t put forward any oligarchs as representatives. He noted the party would send 400 candidates to Russia’s 450-strong lower house of parliament, but expected to get about 12 percent of the seats.
He also said that Communists of Russia did not plan to discuss their program and moves with capitalists and the party of power, but promised to hold talks with the Communist Party of the Russian Federation (KPRF) if the leading Russian opposition party shows any interest in cooperation.
Sergey Obukhov, a member of Russia’s Communist Party, called the proposal to discuss joint projects with the Communists of Russia “not serious, to say the least.” He added that Suraikin’s program was a precise copy of the 10 steps to bring the country out of the crisis recently put forward by KPRF leader Gennadiy Zyuganov.
Obukhov went on to call Communists of Russia “a fake party with a fake program.”
Communists of Russia cannot claim any significant public support, but they never fail to grab headlines in the mass media by dint of various bizarre suggestions and quick reactions to the latest fads.
Recent stunts include: the threat to launch mass protests if US actor Leonardo Di Caprio gets to play Vladimir Lenin; a proposal to ban handheld monopods, aka ‘selfie sticks’ at street celebrations on Victory Day; an initiative to bar US athletes from participating in the 2014 Sochi Olympics, and a plea to the Central Bank to restrict sales of foreign currency to citizens. | 2023-09-19T01:26:28.774034 | https://example.com/article/1220 |
List of children's television channels in South Asia
This is a list of kids channels in South Asia.
Bangladesh
Pakistan
Sri Lanka
India
Defunct
Programming Blocks
India
Pakistan
References
Category:Lists of television channels
. | 2023-09-27T01:26:28.774034 | https://example.com/article/1904 |
Isolation, characterization, and structure of a mutant 89 Arg----Cys bisphosphoglycerate mutase. Implication of the active site in the mutation.
Bisphosphoglycerate mutase (EC 5.4.2.4.) is a trifunctional enzyme which displays synthase, mutase, and phosphatase activities. The purification, characterization, and structural study of an abnormal form of the enzyme, isolated from a patient which we reported earlier (Rosa, R., Prehu, M. O., Beuzard, Y., and Rosa, J. (1978) J. Clin. Invest. 62, 907-915), is described. The abnormal enzyme, present at 50% of the level of the normal enzyme as estimated by immunological methods, showed elevated electrophoretic mobility and hybridized with erythrocyte phosphoglycerate mutase (EC 5.4.2.1.) in the same manner as the normal control. The mutant enzyme was unstable at 55 degrees C and could be protected against thermal instability by 0.5 mM glycerate 2,3-bisphoshate but not by either glycerate 3-phosphate or glycolate 2-phosphate. Two of the three functions of the mutant enzyme were distinct from those of the normal protein. The specific activity of the synthase was 0.57% of normal and that of the mutase 4.1%. By contrast, the specific phosphatase activity was not affected by the mutation. However, the phosphatase activity of the mutated protein was markedly less stimulated by glycolate-2-phosphate than that of the control. High performance liquid chromatography analysis of tryptic peptides derived from the mutant enzyme showed an abnormal profile with the absence of two peaks normally containing the T12 and T13 peptides and without the appearance of a supplementary peak. Amino acid sequence and mass spectrometric analysis demonstrated the substitution of Arg----Cys residue in position 89 producing an uncleaved T12-T13 present in the same peak as the T6. Considered together, our data suggest that Arg-89 is located at or near the active site of bisphosphoglycerate mutase and that this residue is probably involved in the binding of monophosphoglycerates. | 2023-10-12T01:26:28.774034 | https://example.com/article/8769 |
FAIRFIELD, Iowa — The Clinton camp says Bernie Sanders is scared. The Sanders campaign says Hillary Clinton is desperate.
It’s part of a game of debate one-upmanship that’s preoccupied the two leading Democrats in the final days leading up to the Iowa caucuses.
The candidate debates – or lack of them -- have been a persistent issue throughout the campaign. But in recent days, the two camps have been engaged in a back-and-forth that reveals how much has changed since the grumbling began months ago – and how freighted the debate issue has become.
The latest flare-up began Tuesday after the Union Leader newspaper and MSNBC announced they would host a New Hampshire Democratic debate. It made business sense for both: Each outlet had recently lost Republican debates that they had been scheduled to host.
It made sense for the Clinton campaign, too: Looking back at her strong early debate performances, some of Clinton’s top advisers have privately expressed regret over not pushing for more debates earlier — despite the fact that her team had initially wanted fewer than the six official debates that were eventually scheduled. There was also a push to increase Clinton’s visibility since the weekend of the last debate two week ago in South Carolina, according to several sources familiar with the conversations.
As Sanders gained on her in Iowa and solidified his lead in New Hampshire, they said, the unpleasant memories of 2008 loomed large.
“There was a shift a week to ten days ago,” said one person close to the campaign team. “It was the realization that this is a real race."
Clinton herself went on television to point out her willingness to have additional debates – and when the Sanders campaign remained silent, her campaign turned the screws.
“The Sanders campaign is the one holdout,” said Clinton press secretary Brian Fallon on CNN Wednesday. “We think they should join us in saying that they’ll be there in New Hampshire next week."
If the incentives for Clinton to immediately agree to additional debates are clear, they aren’t as obvious to the Sanders campaign now that it’s running neck-and-neck with Clinton in Iowa and leading in New Hampshire.
Sanders himself bristles at the idea that he’s been portrayed as a debate dodger, given the limited number of Democratic National Committee-sanctioned debates and his earlier calls for more debates.
“Anybody who looks at the number of debates that were scheduled, and when they were scheduled [understands the intention]. I think the debate here in Iowa was on the night of the University of Iowa-Iowa State football game,” said Sanders at a breakfast with reporters Wednesday, echoing his campaign’s contention that the national party hasn’t been a fair broker when it comes to the debates. “It is obvious. Of course the establishment is for Secretary Clinton, that’s not a debate."
Yet the campaign’s initial foot-dragging in agreeing to the newly-scheduled Union Leader/MSNBC debate led to a pummeling from influential liberals like Rachel Maddow — a would-be moderator. An unflattering storyline emerged, pushed by Clinton and her allies, that this was the move of a cautious, calculating politician.
“How ironic that when the pressure’s on, Senator Sanders is acting like a typical establishment candidate and refusing to debate,” said Clinton fundraiser and DNC member Robert Zimmerman at the time.
By Wednesday afternoon, flying back to Iowa from his Oval Office meeting with President Barack Obama, Sanders and his advisers hammered out their response -- a statement agreeing to the new debate, but on the condition that Clinton agree to three further new ones in March, April, and May.
“This idea that Bernie Sanders doesn’t want to debate is ridiculous,” Sanders’ chief strategist Tad Devine explained Thursday. “We’ve been saying since the beginning there should be more. The debate structure was put in place, we think, to inoculate Hillary Clinton from exposure. That’s why you have a debate on the Saturday night before Christmas. That’s why you have a debate on the Sunday of a holiday weekend, you know?"
The demand for late spring debates was designed to sting -- it flew in the face of the Clinton team’s desire to wrap up the contest in early March after a strong showing in the first multi-state primary on March 1. But the Clinton campaign then called Sanders’ bluff Thursday, insisting in a statement that they’ve always been willing to add additional debates beyond the six scheduled events -- and were ready to begin discussions on scheduling debates in April and May.
Devine insists it’s all a cynical ploy, beginning with the newly-added Feb. 4 New Hampshire debate.
“Now Hillary Clinton and her campaign have decided they’d like to have a debate in New Hampshire?” said Devine. “We think the motivation for that is obvious. She’s trailing in every poll in New Hampshire, so they want to have a debate there." | 2024-07-25T01:26:28.774034 | https://example.com/article/8627 |
The finest tapered nylon, shaped to precision brushes. They will outlast bristle brushes many times over and they wash clean of acrylic gesso with water. The perfect brush for priming your painting surfaces! | 2024-03-09T01:26:28.774034 | https://example.com/article/9421 |
Q:
Finger push ups
Push ups variation where you support your body on fingertips, does this variation actually build forearm strength ir is it mostly about pain tolerance to the skin being pressed by the sharp finger bones?
A:
If you're strong enough to take them yes, but if you're not quite there yet, I wouldn't risk it. The stress you put on the small bones and joints in your fingers is immense.
As they are done on the fingers this is trained for the martial arts, it makes the fingers and bones in fingers very strong and hard.
In Kung fu they are trained to do push up on fingers and feast.
But it is very risky as it can damage fingers, which can result in a lot of pain.
These are one of the hardest and most advanced push-up varieties around. Basically, you're doing a regular push-up, but your palms are lifted off the ground and your weight is being supported on your finger pads. This takes an incredible amount of finger and forearm strength, but you can work up to it by doing short plank holds on your fingertips.
Check for other kind of pushups from this link
| 2024-03-04T01:26:28.774034 | https://example.com/article/3283 |
The new chairman of North Herts District Council was announced last night - along with the Labour chairmen for two of the authority's area committees.
North Herts District Council chairman John Bishop is congratulated by his predecessor Alan Millard and Mr Millard's wife, Maureen. Picture: June Essex
Kimpton councillor John Bishop is the new chairman of the Conservative-controlled council, with Royston’s Councillor Jean Green becoming vice-chairman.
Lynda Needham and Julian Cunningham remain leader and deputy leader, with Councillor David Barnard appointed to the cabinet as executive member for leisure and green issues.
Mr Bishop said he was thrilled to represent the district council as chairman, and congratulated his predecessor Alan Millard on raising £3,130 for his chosen charities over the past year.
He added: “I greatly look forward to starting my duties as chairman and aim to live up to the high standards set by my predecessor.”
Outgoing North Herts District Council chairman Alan Millard with a £1,000 cheque from Willmott Dixon's Tony Shevlane and Steven Roberts, which will go to Snappy G's Youth Club. Picture: NHDC
Before the Letchworth meeting for all district council members, construction firm Willmott Dixon presented Mr Millard with a cheque for £1,000 raised by the company for one of his chosen charities, Snappy G’s Youth Club.
The district council’s Labour group gained control of Hitchin and Letchworth committees as the Conservative majority lost five seats in this month’s local elections – two to Labour and three to the Liberal Democrats.
The Hitchin area committee is now chaired by Councillor Ian Albert, with Councillor Clare Billing as vice-chairman. Councillors Gary Grindal and Helen Oliver have taken up the equivalent roles in Letchworth.
The Conservative group also agreed to have Labour councillor Elizabeth Dennis-Harburg as vice-chairman of the district council’s overview and scrutiny committee.
Labour's Ian Albert is the new chairman of North Herts District Council's Hitchin committee, while Elizabeth Dennis-Harburg has become Overview and Scrutiny vice-chairman. Picture: Archant
Mr Albert told this paper: “These are welcome changes and reflect the new balance on the council. We hope that this will lead to far more collaboration and transparency on the district council, and to using the talents of councillors of all parties far more effectively in future.”
He added that it was vital his committee worked across party lines to “represent a strong and united voice for Hitchin”.
The Baldock and District, Southern Rural and Royston area committees remain under Conservative control. | 2024-02-16T01:26:28.774034 | https://example.com/article/9196 |
This is one finding shared in a report from the Pakistan Technical Advisory Group (TAG) on Poliomyelitis Eradication, which met in Islamabad from November 27-28 2013. The objectives of the meeting were to: review progress towards poliomyelitis eradication in Pakistan since the last TAG meeting in December 2012, discuss activities planned for 2014 (in particular, planning for the forthcoming low transmission season), and make recommendations to address the constraints facing Pakistan on the way to achieving the goal of eradication. Though there are challenges, the TAG believes that poliovirus can be eradicated from Pakistan, provided that solutions are found for immunising children in currently inaccessible areas.
The context, in brief: The number of cases in 2013 (at the time of this meeting) had already overtaken the total number of cases reported in 2012, making Pakistan the only one of the three remaining endemic countries to experience an increase of cases in 2013. "Violence against vaccinators and their security escorts has created a climate of threat and uncertainty....There remains a significant risk that poliovirus will continue to move into polio-free areas within Pakistan and beyond."
"Despite an environment that is hostile to vaccination in some areas of Pakistan, the communication programme has made advances in creating an enabling environment. A highly engaged media generated over 6,400 national articles focusing on polio in 2013; the highest market share globally. Among these, less than 5% of Urdu and English press portrayed the programme negatively. Caregiver refusal rates were reduced by over 40% in one year, and the proportion of these due to religious reasons reduced particularly in KP [Khyber Pakhtunkhwa], where there was a large focus on religious advocacy. Acceptance of polio immunization in the general community is higher than it has ever been, with less than 0.5% of caregivers refusing the vaccine. Political, social, and religious leaders and groups have become more active and visible supporters of the eradication goal."
Recent developments have required a shift in communication strategy. Previously, a high-visibility approach focused on public information about polio through media and door-to-door social mobilisation. Then, the communications approach moved to indirect methods, focusing on raising awareness about vaccine-preventable diseases and promoting polio vaccination within a wider context of immunisation.
"With over 80% of polio cases originating from only four Pashtun tribes, the communications effort in 2014 must focus more intensively on building trust for immunization services among these highest risk groups. The programme must ensure adequate representation of these groups in as vaccinators, social mobilizers and community influencers, and in mass media messaging." Specific recommendations are outlined in the report. One focus area involves engaging communities and building demand:
"A strategic, consistent campaign to profile vaccinators and frontline workers as protectors of children should be developed and launched as soon as possible.
A Civil Society Coalition that creates a participatory and independent social movement for polio eradication should be build, with particular emphasis on private sector, private practitioners and potential alternative service providers.
Pashtun voices should be amplified in the national and local media discourse to increase local ownership for immunization.
Concrete steps should be taken to expand COMNet's [the Communication Network for Polio Eradication's] capacity to reach unavailable children; and the proportion of children converted from missed due to child not available to vaccinated, should be added as a key performance indicator of vaccination teams where COMNet staff are working. The programme should also find ways to effectively address refusals and 'not available' children in areas where COMNet is not present.
In areas that remain inaccessible to polio teams, the social mobilization network should utilize its local staff to map potential opportunities to reach children through alternative mechanisms: through stocking health facilities with vaccine and promoting routine services, mapping of midwives or other trusted health workers that have access to children, and more robust strategies to reach children during migration.
GPEI [Global Polio Eradication Initiative] protocols for joint micro-planning should be implemented and monitored...to ensure high-risk children are consistently included in micro-plans.
A communication strategy and localized plans should be established to: Reach children in inaccessible areas and support activities should access be achieved; support the SIAD [short interval additional dose] strategy; and support the introduction of IPV [inactivated polio vaccine]."
Promote your Classifieds
The Communication Initiative's Market Place for International Development supports organisations and individuals in the network to market opportunities and services from which they will directly benefit. All other parts of The CI platforms are of course completely free and open. Please click below for Market Place processes and opportunities that could be of interest to you and your organisation ... or email Victoria Martin. | 2024-05-30T01:26:28.774034 | https://example.com/article/8305 |
[Study on efficiency of nitrogen and phosphorus removal by algal biofilm].
Cultivating algal biofilm on nitrogen (N) and phosphorus (P) in waters presents an alternative to control eutrophication. Under laboratory conditions, efficiency on nitrogen and phosphorus removal from synthetic wastewater, secondary effluent and eutrophic lake water by algal biofilm was assessed. Algal biofilm was mainly composed of blue-green algal species Oscillatoria princeps. During a 5-day treatment, for synthetic wastewater, secondary effluent and eutrophic lake water, removal rates of TN were 57.1%, 94.5% and 93.8%, respectively, removal rates of TP were 93%, 73% and 79%, respectively. The dried algal production were 3.7 - 7.2 g x m(-2)x d(-1), and the TKN and TP of algal biomass were 5.7% - 7.2% and 0.78% - 2.44%, respectively. Recovery of nutrients in harvested algal biomass accounted for about 20% - 39% for N and 65% - 82% for P. | 2024-02-24T01:26:28.774034 | https://example.com/article/8719 |
Q:
What is the way to access object that is outside of #each in meteor template
I am new to Meteor and got stuck here.
<h1>{{otherObj.category}}</h1>
{{#each partners}}
<p>{{name}} - {{otherObj.category}}</p>
{{/each}}
In this template snippet, otherObj is the object that i want to access in the loop. So this outputs
<h1>football</h1>
<p>Name1 - </p>
<p>Name2 - </p>
Further investigation revealed that OtherObj inside the loop is 'undefined'
Any idea, how can i access it inside the loop ?
A:
You need access to parent properties of each loop.
Use ../ like this :
<h1>{{otherObj.category}}</h1>
{{#each partners}}
<p>{{name}} - {{../otherObj.category}}</p>
{{/each}}
| 2023-10-31T01:26:28.774034 | https://example.com/article/4231 |
Q:
Fundamental matrix solution and Floquet theory
Let the following matrix problem be given
$$y'=M(t)y$$
where $y\in\mathbb{R}^n$ and $M(t+a)=M(t)$ for some $a>0$. So $M$ is periodic.
A fundamental matrix solution can be written as $X(t)=f(t)e^{At}$, where $f(t)$ is a $a$-periodic $n\times n$-matrix and $A$ a constant $n\times n$-matrix.
For $n=1$ and $n=2$:
1. How do I find $A$?
2. What must hold for $M(t)$ such that all solutions remain bounded when $t\rightarrow \pm \infty$?
3. What must hold for $M(t)$ such that all solutions are $a$-periodic?
Here $M(t)=m(t)\begin{pmatrix}a&b\\c&d\end{pmatrix}$ for $n=2$ with $m(t)$ again $a$-periodic and $a,b,c,d$ constants.
What I thought:
For $n=1$ you want to find
$$X'=M(t)X$$
where $X(t)=f(t)e^{At}$. So this gives us
$$f'(t)+Af(t)=M(t)f(t)$$
where $A$ is just a real number. How do I find it? And what must I do for the conditions in 2. and 3.?
For $n=2$ I would appreciate any hints.
A:
These are several different questions that need extensive space to be answered in detail. I will only provide an outline of some key points.
The matrix $A$ can be directly calculated from the relation
$$X(a)=f(a)e^{aA}=f(0)e^{aA}=e^{aA}$$
where the property $f(0)=\mathbb{I}$ has been used that follows from the fact that $X(0)=\mathbb{I}$. Thus, the general approach is to find $A$ from
$$A=\frac{1}{a}\ln(X(a))$$
but calculating $X(a)$ is a tedious task for most cases.
However, for $n=1$ the fundamendal "matrix" (scalar in this case) takes the simple form
$$X(t)=\exp\left(\int_0^t{M(s)ds}\right)\qquad\qquad \qquad(1)$$
This solution can be easily checked that satisfies the ODE $X'=M(t)X$. As a result $A$ in this case is given by
$$A=\frac{1}{a}\int_0^a{M(s)ds}\qquad\qquad \qquad(2)$$
Also, for a general dimension $n$, if $M(t)M(\tau)=M(\tau)M(t)$ for all $t,\tau$ (which is the case for your $n=2$ function $M(t)$) then (1), (2) also hold true.
For boundedness of the solutions as $t\rightarrow+\infty$ all eigenvalues of $e^{aA}$ should lie inside or on the unit circle. Note that the solution of $y'=M(t)y$ at times $t=ka$ is given by
$$y(ka)= (e^{aA})^ky (0)$$
Thus, what is needed is $\|(e^{aA})^k\|$ to remain bounded which is the case if all eigenvalues of $e^{aA}$ should lie inside or on the unit circle (Edit: for repeated eigenvalues on the unit cycle, their eigenvectors need to also be linear independent). In fact if all eigenvalues of $e^{aA}$ lie within the unit circle then all solutions tend to zero as $t\rightarrow+\infty$. Reversing now time and going for $t\rightarrow -\infty$ you will need to change the conditions accordingly.
This property is valid for all initial conditions if and only if
$$e^{aA}=\mathbb{I}$$
Assume $y(t)$ a solution for some $y(0)$. Then $y(t)=f(t)e^{At}y(0)$ and
$$y(t+a)=f(t+a)e^{A(t+a)}y(0)=f(t)e^{aA}e^{At}y(0)$$
We want $y(t+a)=y(t)$ or equivalently
$$f(t)e^{aA}e^{At}y(0)=f(t)e^{At}y(0)$$
$f(t)$ is an invertible matrix which yields
$$e^{aA}e^{At}y(0)=e^{At}y(0)$$
and for $t=0$ we have
$$e^{aA}y(0)=y(0)$$
Since the above must hold true for all $y(0)$ we can select different initial conditions $y_i(0)$ such that $[y_1(0),y_2(0),\cdots,y_n(0)]=\mathbb{I}$ and
$$e^{aA}=e^{aA}[y_1(0),y_2(0),\cdots,y_n(0)]=[e^{aA}y_1(0),e^{aA}y_2(0),\cdots,e^{aA}y_n(0)]=[y_1(0),y_2(0),\cdots,y_n(0)]=\mathbb{I}$$
It is easy to prove that this is also a sufficient condition.
| 2024-04-07T01:26:28.774034 | https://example.com/article/7623 |
Photo credit: Matthew Yohe/Wikipedia (CC BY-SA 3.0)
Although he’s arguably one of the most influential geniuses of our time, he had a shockingly repulsive go-to routine to relieve his stress.
Film critics and media outlets aren’t very impressed with the new Steve Jobs movie that hit theatres over the weekend. According to Engadget, it only raked in about $7.3 million at the box office and will likely struggle to turn a profit. However, all flashy movie dramas aside, Steve Jobs is one of the most influential humans of our time. He probably doesn’t cross your mind everyday, but that little device that’s glued to your hand is his legacy.
SEE ALSO: 7 Scientists Who Never Got the Credit They Deserved
Steve Jobs was, like most geniuses, incredibly complex. His personality and life story is peppered with bizzarities and truths that you probably wouldn’t expect of the man behind Apple.
1. He refused Apple CEO Tim Cook’s offer for a liver transplant.
It’s no surprise that Steve Jobs had a close friendship with Apple CEO Tim Cook. So close, in fact, that when Steve Jobs was sick, Cook offered to donate a portion of his liver to him. The authors of Becoming Steve Jobs, Brent Schlender and Rick Tetzeli, report that Jobs didn’t even entertain the thought, immediately and angrily turning down the offer. He never went on to have a liver transplant.
2. He soaked his feet in toilet water as a stress-reliever.
This is probably the strangest one on the list. According to his authorized biography written by Walter Isaacson (Steve Jobs), one of the tech guru’s go-to stress relievers during the early days of Apple was to head to the company toilets and soak his bare feet in the toilet water. In fact, the guy had a little bit of a hygiene problem — Isaacson also revealed how Jobs was put on the night shift while he worked at game-maker Atari because he rarely bathed and would walk around the office in his bare feet.
3. He was an LSD advocate.
Most extremely influential people in the public eye tend to shy away from associating themselves with illegal drugs. Jobs, on the other hand, made his endorsement of the hallucinogenic drug acid open. In fact, he said his LSD experience was, “one of the two or three most important things I have done in my life.” Plus, considering Apple’s slogan was “Think Different,” it seems as though his psychedelic experience helped Jobs tap into the innovative and creative parts of his brain. Dreaming up the technological empire that would become Apple certainly required some thinking outside the box.
4. His business methods were inspired by The Beatles.
The Beatles are timeless icons for the virtues of peace, love, and equality… things that aren’t typically associated with business. Nonetheless, the hippie dreamers inspired Steve Jobs’ ideas in the business world. “My model for business is The Beatles. They were four guys who kept each other’s kind of negative tendencies in check,” he said. “They balanced each other and the total was greater than the sum of the parts. That’s how I see business: great things in business are never done by one person, they’re done by a team of people.”
5. Having kids made him more empathetic when it came to firing people.
According to Schlender and Tetzeli’s book, Steve Jobs found it much harder to fire people after he had kids. Jobs is notorious for his ruthless leadership in the workforce (he’s fired people on the spot in front of crowds), but he also was a big family guy. He said after having kids, he could imagine others as being 5 years old. “And I think that that could be me coming home to tell my wife and kids that I just got laid off. Or that it could be one of my kids in 20 years. I never took it so personally before,” Jobs confessed.
Even if the new Steve Jobs movie flopped at the box office, we still love him for all of the things he’s done for the field of technology — and for all of his quirky attributes that made him human. He was a college dropout, a little hygienically-challenged, and had a short temper, but his ambition and innovative spirit persevered onwards to transform the world. | 2024-03-21T01:26:28.774034 | https://example.com/article/8449 |
Archive for the ‘Bank Of America Mortgage’ Category
Banks and other lenders don’t benefit from foreclosure, and they prefer not to be involved in it, but if the borrower can’t pay the are forced to take back the property and sell it to recover their funds. In avoiding such mistakes or any troubles on mortgage debt and foreclosures, we must able to know what to do and learn from any various ways what should be done to have the more safer and legality for the banks. It has been said to have a loan to make sure that your credits are up to follow.
We have here a short listings about the and how it turned out not only for the market but for almost the world:
If all fifty states were to sign on to the settlement, Brown’s office estimates (forty-four have so far), it would provide $8.68 billion in reduced payments and fee waivers to some 400,000 Countrywide borrowers struggling to stay in their homes. And a small Foreclosure Relief Fund of $150 million would provide direct payments to Countrywide borrowers who have already lost their homes to foreclosure.
In fact, the settlement has functioned more as loss mitigation for than as recompense for victims of predatory lending, says Alan White, an associate professor of law at Valparaiso University and an expert on the subprime crisis.
Countrywide borrowers facing foreclosure have not even been notified that they may qualify for the settlement. It has kept, at best, about 134,000 families in their homes, and most
of these only temporarily.
Imagine that your home to be disclosed and will have no. It is better to have a solidarity in each things and finding solutions like settlements. So that’s why you should know the programs and regulations so that you can able to avoid any foreclosures. Make a listings and refer all the necessary ways with your plan so that you can able to attain every payment check on the bank.
Here on we give you knowledge and ideas on what is going on around the foreclosure areas around the world to help you what you are looking for and what you want to know on the current events and news that is reliable to avoid and stop foreclosure.
Apple acquired hopstop in 2013 in an effort to improve its own transit directions in apple maps, and with those improvements coming online when ios 9 launches on https://cellspyapps.org/ sept
Hello everybody Jesse Moore here with Pickett Street Properties, where we are redefining real estate in Seattle, thanks for testing my weblog today. Our team of short sale experts is dedicated to helping Seattle area homeowners avoid foreclosure and I use my blog to share my data on up to date Seattle short sale news. In case you are behind on your mortgage, or already contemplating a short sale, please stop by my web site or contact me at present to discuss your choices for avoid foreclosure.
For my blog immediately I wanted to go over the recent settlement involving Bank of America and the issue of robo-signing on some loans. We’re finally beginning to get more details and there are more lenders concerned than simply Bank of America. The five largest lenders within the nation have settled with the federal government and agreed to offer principal reductions as much as one hundred thousand dollars. There are some guidelines sadly and the most important one is that your loan cannot be owned by a government entity reminiscent of Fannie Mae, Freddie Mac, or the FHA. This means out of all Bank of America mortgage holders may be twenty percent of them would qualify for this principal reduction. Hopefully there are a variety of Seattle owners in that twenty percent who have been not directly effected by this settlement. If you are currently underwater this settlement might help you out however a short sale may be your best choice in the long run.
This was a really brief clarification of the Bank of America settlement and you probably have any questions about it, or the short sale process, please give me a call or stop by our places of work today. Thank you for your time and I look forward to hearing from you soon at Seattle’s leading short sale specialists at Pickett Street Properties.
For more information on short sales and how to avoid foreclosure, or you can also and get started today. | 2024-04-06T01:26:28.774034 | https://example.com/article/4410 |
00*a**4
Expand (-2 + 3 - 2)*(-m + 0*m + 2*m + (-4*m + 0*m + m)*(0 - 5 - 5) + 2*m + m - 2*m - m + 2 - 2) + (-2*m - 5 + 5)*(5 + 3 + 0).
-47*m
Expand (152 + 145 + 46 - 1535*k - 343)*(-3*k**2 - k**2 + k**2).
4605*k**3
Expand (-l - 7 - 419*l**3 + 421*l**3 + 2*l)*(28 + 0 - 2).
52*l**3 + 26*l - 182
Expand (2*u + 3 - 3)*(-u**3 + 0*u**3 - 3*u**3) - 6476 + 129*u**4 + 6476 - u**3 + 2*u**4 + u**3.
123*u**4
Expand (-17*t - 9*t + 12*t)*(18*t + 23*t - 3*t).
-532*t**2
Expand (1417*h - 534*h - 1015 + 1021*h + 1015)*(1 - 6 + 1).
-7616*h
Expand -20 + 20 + k**3 + (3*k + 0*k + 6*k)*(-2*k**2 + 13*k**2 - 3*k**2).
73*k**3
Expand (58 + 48*f - 58)*(-3 + 0 + 2) + (2609 - 2609 + 29*f)*(-2 - 2 + 6).
10*f
Expand (96*z**2 + 2*z**5 + 17379*z**4 - 17379*z**4)*(9 + 0 + 4).
26*z**5 + 1248*z**2
Expand (3*k - 14*k - 3*k)*(-1529*k - 84*k**3 + 1529*k).
1176*k**4
Expand (-88 + 155 + 91 + 80)*(69*h**2 + 113*h**5 - 69*h**2).
26894*h**5
Expand (13*q - 7*q - 21*q)*(1082*q + 12362 - 12362) - q**2 - 2 + 4 + 0.
-16231*q**2 + 2
Expand (1 - 1 - 2*j**3)*(j + 2*j - j) + (-2*j + 5*j - j)*(-j**3 + 0*j**2 + 0*j**2) - 4*j**4 + j**4 + 4*j**4 + (3*j**2 + 3 - 3)*(-j**2 + 9*j**2 + j**2).
22*j**4
Expand (0 + 2 + 1)*(-3113*k + 1731*k - 670*k).
-6156*k
Expand (5*h**2 + 5*h - 5*h)*(654*h + 1008*h - 10264 - 2*h**2 + 10265).
-10*h**4 + 8310*h**3 + 5*h**2
Expand (-1381 - 1146 - 1174 + 269)*(0 + 0 - w).
3432*w
Expand 2*u**3 + 3*u**4 - 2*u**3 + (39*u - 67*u - 32*u + (0 - 2 + 3)*(4*u + 0*u - 5*u))*(15*u + 2803*u**3 - 4*u - 2804*u**3).
64*u**4 - 671*u**2
Expand -2*k**5 - 11*k**2 + 11*k**2 + k**2 - 2*k**5 - k**2 + (0*k - 2*k + 3*k)*(-3*k**4 + 2*k**4 + 3*k**4) + 16*k**5 + 12*k**5 - 17*k**5 - 1.
9*k**5 - 1
Expand (-4529 + 4529 - 10*x)*(-1 + 1 - 2)*(-5*x - 3 + 3) - 14*x**2 + 5*x**2 + 4*x - 5*x.
-109*x**2 - x
Expand (-3 + 9 - 5*j - 3)*(-22*j + 11*j - 14*j)*(-j + 5 - 5)*(-3 + 5 + 1).
-375*j**3 + 225*j**2
Expand 0*z**5 + z**5 + 0*z**5 + 1 - 3 - 6*z**5 + 7*z**5 + (-z**3 + z**3 + 2*z**3)*(4*z**2 + 0*z**2 - 11*z**2) + 4*z**3 - 4*z**5 - 4*z**3.
-16*z**5 - 2
Expand (4*q - 6*q + 15*q)*(-1 - 1 + 3)*(-61 + 282 + 276).
6461*q
Expand ((-2*t**2 - 3*t**2 + 4*t**2)*(-3*t + t + 0*t) + t**3 - 11*t**3 + 0*t**3 + t**3 + 1 - 1)*(41*t + 108*t + 167*t).
-2212*t**4
Expand 2*y + y + 0*y + (-1 + 0 - 1)*(-1 + 1 + y) - 141*y - 109*y - 1 + 94*y.
-155*y - 1
Expand (-3*r**2 + 7850 - 7841 - r**2 - 4*r)*(6*r**3 - 17*r**3 + 20*r**3).
-36*r**5 - 36*r**4 + 81*r**3
Expand 2*t**5 + t**5 - 6*t**5 + (3*t**4 + 0*t**4 - 5*t**4)*(t - 2*t - t) + 4*t**5 - t**5 - t**5 + 9328683*t**4 - 114*t**5 - 2*t**2 - 9328683*t**4 + 2 - 8*t.
-111*t**5 - 2*t**2 - 8*t + 2
Expand (224 - 565*a - 566*a + 1132*a)*(a + 2*a + a).
4*a**2 + 896*a
Expand (-3*u + 3*u - 2*u)*(-15172*u**2 + 15172*u**2 + 93*u**3)*(u - 5*u + 34 - 33) - u**5 + 6*u**5 - 3*u**5.
746*u**5 - 186*u**4
Expand (5*d + 13*d - 3*d)*(-5*d**3 + 9*d**3 + 3*d**3) - 1 + 19*d**2 - 6*d**4 - 24*d**2 + 3.
99*d**4 - 5*d**2 + 2
Expand (-2*k**2 - 4*k**2 + 5*k**2)*(-9 - 5*k**3 + 9 + (-k**2 - 2*k**2 - k**2)*(-11 + 22 - 8 + k)).
9*k**5 + 12*k**4
Expand (1 - 27*y**3 - 1 + (0*y + y - 3*y)*(-4*y**2 + 3*y**2 + 7*y**2))*(0 + 2 - 1 + (3 - 2 + 0)*(-1 - 2 + 6) - 5 + 0 + 2).
-39*y**3
Expand (3*b - 3*b - b**3)*(6*b - 2*b - 3*b)*(-2 + 5 - 4)*(7*b - 6*b + 6*b).
7*b**5
Expand 2 + 1042716*t**2 + 7 - 1042715*t**2 + 11*t + (5*t - 4*t + 0*t)*(4*t - 2*t - 3*t) - t**2 - t + t + 4 - 4 + t**2 - t + t + 2*t**2.
2*t**2 + 11*t + 9
Expand (v**2 + v**2 + 0*v**2)*(922*v**2 - 176*v + 90*v + 86*v).
1844*v**4
Expand (-16*p**3 + 6*p**3 - 14*p**3)*(0 + 1 - 3)*(-18 + 18 + 6*p)*(1 - 5 - 1).
-1440*p**4
Expand (-132*b + 267*b - 141*b + 6)*(-23 + 23 - 9*b).
54*b**2 - 54*b
Expand 98*b**3 + 112*b**3 - 41*b**3 + b**2 - 347*b - 6*b**3 - 2 + 347*b + (5*b - 5*b + 2*b**3)*(-2 + 4 - 1).
165*b**3 + b**2 - 2
Expand (-c**3 + 5*c**2 - 5*c**2)*((9*c + 5*c - 13*c)*(-2*c - 3*c - 16*c) + 1 + 2*c**2 - 1 + 3 + 2*c**2 - 3).
17*c**5
Expand (-5284 + 2058 + 2195)*(0*v + 5*v + v).
-6186*v
Expand (3*i + 79 + 173 + 38 + 5*i + 0*i)*(-i - 2*i - 5*i).
-64*i**2 - 2320*i
Expand (3*g + g - 2*g)*(-4 - 3 + 4) + 882 + 77*g + 74*g - 150*g.
-5*g + 882
Expand -f**4 + 4*f**4 - 2*f**4 + (-1 + 1 + f)*(2*f**3 + 3*f**2 - 3*f**2) - 2 - 2*f**4 + 2 + (1571*f - 1571*f + 79*f**4)*(3 - 1 - 1).
80*f**4
Expand (39*b - 14*b + 7*b)*(5*b**4 - 6*b**4 - 6*b**4) + (-3*b + 3*b + 2*b**4)*(-21*b - b + 34*b) - 2*b**5 - 2*b**5 + 7*b**5.
-197*b**5
Expand (-39*u + 80*u + 59*u)*(-3 - 4 + 5) + (0*u - u - u)*(-6 + 5 - 8).
-182*u
Expand 3*l**2 - 3*l**2 - l**4 + (-4*l**3 + 5*l**3 - 2*l**3)*(l - 66*l - 197*l).
261*l**4
Expand (3 + 1 - 3)*(-y**5 - 2*y**5 + y**5) + 1 - 3*y**5 - 1 + 4*y**5 - y**5 - y**5 + 364*y**2 + 188*y**5 - 183*y**2 - 181*y**2.
185*y**5
Expand (-920*c**3 + 161*c**3 - 466*c**3)*(-2 + 1 + 2).
-1225*c**3
Expand (-m + m - m)*(-28*m**2 - 172076 + 2*m + 172076 + 24*m**3) - 2*m**4 + 2*m**3 - 2*m**3.
-26*m**4 + 28*m**3 - 2*m**2
Expand ((-1 + 4 - 2)*(-l**3 - 2*l**3 + 10*l**3) + 273*l - 11*l**3 - 273*l)*(-3*l + 0*l + 5*l - 3*l - l + 2*l + (1 - 1 + l)*(2 - 3 - 1)).
8*l**4
Expand (3 - 9 + 5)*(-53 - 39*q + 53)*(2*q**3 + 4*q**3 - q**3) + 3*q**4 - q**4 + 0*q**4.
197*q**4
Expand (5*q + 0 + 0)*(2*q**2 + 7*q**2 - 3*q**2 + (3*q + 2*q - 2*q)*(-6*q - 2*q + 0*q)).
-90*q**3
Expand ((0 - 7 - 3)*(p + p - 3*p) + (4 + 3 - 5)*(0*p - 2*p + 0*p))*(-74*p - 59 + 59).
-444*p**2
Expand (4*o + 2*o - 4*o)*(2*o + o - 5*o) + 2*o**2 + 0*o**2 - o**2 + 192*o**2 - 426*o**2 + 172*o**2.
-65*o**2
Expand 21*w**5 - 2827 - 2829 + 5657 + (-w + 3*w + 0*w)*(-2*w**4 - 2*w + 2*w).
17*w**5 + 1
Expand (2248 - 37*a - 1127 - 1124)*(-4 + a + 5 + 0*a).
-37*a**2 - 40*a - 3
Expand (1 + 0 + 1)*(h - h + h + (-1 - 1 + 1)*(5 + 4 - 2)*(-444 - 145*h + 444)).
2032*h
Expand (-5*w - w + 2*w)*(-4 - 5 + 6) - 7*w - 16*w - w - w - 3*w + 3*w.
-13*w
Expand (39*n**2 + 3*n**2 - 4*n**2)*((3*n - 4*n + 0*n)*(-2 - 2*n + 2) + 45*n**2 - 12*n**2 - 7*n**2).
1064*n**4
Expand (2*o - 3*o + 5*o)*(3*o - o + 0*o) - 12 + 13 + 0*o**2 - 9*o**2.
-o**2 + 1
Expand (-6*i + 18 - 18)*(1 + 31 - 151) + i + 3*i - 2*i.
716*i
Expand -51*u**2 + 51*u**2 - 37*u**3 + 0 + 2*u**3 + 0 - u**3 + 5*u**3 - 3*u**3 - 4*u + u**3 + 4*u + (4*u - 3*u + u)*(u**2 + u**2 - u**2) + 12*u**3 + 37*u - 37*u.
-19*u**3
Expand 92 - 92 + 12*s**2 + (0*s + 0*s + 4*s)*(-s + 2*s - 3*s) + 2*s - 2*s + 2*s**2 + 0*s + 0*s - 3*s**2.
3*s**2
Expand (16*c + 0*c + 4*c)*(-18*c - 165 + 165) + 3*c**2 - 7*c**2 + 2*c**2.
-362*c**2
Expand (5*c**2 - 3*c**2 - c**2)*(-4 + 2*c + 4)*(0*c + c - 3*c) + (-2*c**3 - 3*c**3 + 7*c**3)*(-2*c + 0*c + 3*c).
-2*c**4
Expand -2*j**4 + 3*j - 3*j + 2*j**2 + 2*j**4 - 2*j**2 + (2*j**3 + 4 - 4)*(j - j - 2*j) + 0*j**4 + j**4 + 0*j**4 - 73*j**4 - 1028*j**2 + 514*j**2 + 515*j**2 + 1.
-76*j**4 + j**2 + 1
Expand (-140*w + 185*w + 306*w)*(-1 + 9 - 4) + w + 0*w + 3*w.
1408*w
Expand (-q**3 + 2*q**3 + 0*q**3)*(0 + 0 + q) - 134*q**4 - 2010*q**4 - 119*q**4.
-2262*q**4
Expand (-2*n**3 + n**3 - n**3 - 2*n)*(-37330*n + 83252 - 41628 - 41624).
74660*n**4 + 74660*n**2
Expand (3 - 3 - 1)*((0 - 2 + 0)*(7 - 21 - 30) - 3 + 2 - 1)*(-3*q + 0*q + 2*q)*(7 - 3 - 3).
86*q
Expand (c**3 - 4*c**3 + 2*c**3)*(-4 + 2 + 0) + 4*c**3 - 2062*c**2 + 29 + 2062*c**2.
6*c**3 + 29
Expand 2 - 2 - 3*c**3 + 9*c**3 - 16*c**3 - 17*c**3 + (-2 - 3*c**2 + 2)*(0*c + c + 0*c) + c + c**3 - c + (3 - 3 - 2*c)*(-1 + 1 + 2*c**2) - 12 - c**3 + 12.
-34*c**3
Expand (-2 - 1350*i**3 + 3 + 1472*i**3)*(5*i - 5*i - 1 - 3*i).
-366*i**4 - 122*i**3 - 3*i - 1
Expand 80*q**2 - 57*q**2 + 153*q**2 + 3*q**2 - 10*q**2 + 3*q**2 + (4 - 1 - 1)*(q**2 - 1 + 1).
174*q**2
Expand 2*r**3 + 0*r**3 - 3*r**3 + (4 + 4 + 6)*(2*r + r + 2*r)*(2*r**2 + 9*r**2 - 4*r**2).
489*r**3
Expand 93188*j**2 - 93188*j**2 + 176*j**3 + 6*j**3 - 7*j**3 - 9*j**3 + (6*j - 4*j + 0*j)*(5*j**2 + 0*j**2 - 3*j**2) - j**3 + j**3 - 2*j**3.
168*j**3
Expand (-3 - 5 - 5)*(-973*n**3 - 5247*n**2 + 5247*n**2).
12649*n**3
Expand 29*a**4 - 28*a**5 - 23*a**5 + 52*a**5 - 16 - 19*a**5 + 16 + (0*a - 4*a + 3*a)*(-2 + 2 - a**4).
-17*a**5 + 29*a**4
Expand (-5 + 8*r**2 + 18*r - 38*r + 21*r)*((-1 + 0 - 4)*(4*r**3 - 2*r**3 - r**3) - 5*r**2 + 5*r**2 - 12*r**3).
-136*r**5 - 17*r**4 + 85*r**3
Expand (2*t - 5*t + 5*t)*(-4*t**2 + 95*t**2 - 19*t**2)*(-5*t - t + 0*t).
-864*t**4
Expand -4 + d + 4 + (2*d - 3*d + 3*d)*(-35 - 269 - 195) + (-1 + 1 + 2*d)*(-3 + 0 + 1) - 2 + 2*d + | 2023-08-04T01:26:28.774034 | https://example.com/article/7658 |
Dong Zhuo's body was shown in the market-place. The weather began to get hot, and Dong Zhuo had been big and fat, and his at flowed onto the ground. The men guarding the corpse made a great lamp and set it up on Dong Zhuo's navel and lit it, and it turned clear and bright till dawn. This went on for several days.
And thanks for this thread btw, cracked up some laughs. Jian Yong is definatly my favoruite comedian of the 3k era LOL.
I only just realized (after we talked about monotremes in my biopsychology class... don't ask) that in a chicken, the eggs and the poop come out from the same place (birds have just one opening for things to come out).
"Whatever you do, don't fall off the bridge! It'll be a pain to try to get back up again." - Private, DW 8
4: The Record of Cao Man states: The Great Ancestor in his youth enjoyed flying hawks and racing dogs, endlessly knocking about, such that his uncle spoke to his father Song about his behavior. The Great Ancestor suffered for it, and later when he came upon his uncle along the road, he pretended to be having a seizure; his uncle was bewildered and asked him what was wrong and the Great Ancestor replied, “I am having a stroke.” His uncle therefore went to tell his father Song, who was very startled, and called the Great Ancestor to him, the Great Ancestor then resuming his normal appearance. His father spoke, asking, “Your uncle said that you were having a stroke; are you now recovered?” The Great Ancestor replied, “I never had a stroke in the first place. My uncle has always been lacking in affection for me, thus he has only ever been unpleasant to me.” Song therefore became suspicious. From that moment onward, Song didn’t believe anything that his brother told him regarding the Great Ancestor and the Great Ancestor behaved even more recklessly.
The Lady was married to Huang Yun, but about 172 her husband proposed to divorce her so that he might marry the niece of the Excellency Yuan Wei. She concealed her resentment and arranged a formal ceremony of farewell, but then, before a crowd of his kinsmen and clients she read out a catalogue of his faults, including most intimate matters, then called up her carriage and left. Huang Yun was utterly shamed. -HHS 68/58:2230, HHJ 23: 276.
Plus, astonishing secrets leading to this: Guo Tai warned him to watch his conduct. GUESS WHAT HAPPENED, HUH?
-----------
Gou Yu: Filial Piety as an Excuse for Murder
Gou Yu, the Lady; Chenliu. A woman of family, about 130 she killed her husband's uncle Li Shi to avenge her own uncle. She was arrested and liable to death, but the young scholar Shentu Pan spoke to the magistrate Liang Pei, arguing that even as a woman she had fulfilled the obligations of family vengeance, and praising her conduct as a model for future generations. Liang Pei, deeply impressed, obtained her an official pardon. -HHS 53/43:1751, XHS 4:1b.
-------------------------
MAN DIES FROM SEX WITH WIFE
Dun Zixian. A former commandery Investigator, Dun Zixian became ill but then recovered. He went to the doctor Hua Tuo, who took his pulse and advised him that the sickness was still present and that he must avoid any exertion, including sexual intercourse, as a relapse could kill him. The fatal moment would be known by a protrusion of his tongue for several inches.When Dun Zixian's wife heard he was cured, she traveled a hundred li to care for him. The couple had intercourse, however, and Dun Zixian died three days later, just as Hua Tuo had foretold.
Li Tan; Anping. A Consultant at the Han court under Cao Cao, Li Tan was influenced by the adept Hao Mengjie/Xi Jian and attempted to practice his techniques of long life, including abstention from cereals, eating the "China-root" fungus Pachyma or Porla Cocos, and drinking cold water. He got diarrhoea, however, and very nearly died. -SGZ 29:805.
Concerning the public effects of this fad, "when he came to Cao Cao's court in the early third century, the market price of China-root quickly doubled."------------------------Fief Abolished for Unnatural Incest
Zang Song; Yingchuan. Elder son of Zang Zhen, he succeeded to the family marquisate. In 117 he was found guilty of committing incest with his mother; the fief was ended. -
Cao Rui had a deer park and very strict rules against hunting deer in it (if you did so, you would be put to death). Translated by Achilles Fang in Chronicles of the Three Kingdoms, this part of the Wei ming zhen zou (Collection of Memorials of Famous Ministers of Wei), quoted in SGZ, mentions advice from Gao Rou. Gao Rou's advice employs incredibly hilarious and flawed logic. After I finished typing this up for the other thread, I couldn't stop laughing:
“I have profoundly reflected: The reason why Your Majesty does not take these deer early is that you wish them to multiply to the extreme, when you will take them on a large scale to make them serve army and state. But I presume to think that, as it is, the deer will daily decrease and you will have no chance to get them on a large scale. Why do I think so? Now the Imperial enclosure extends to an area of more than a thousand li. IN my calculation, there are in this area easily 600 tigers, large and small, 500 wolves, and 10,000 foxes. Supposing a large tiger eats one deer every three days, one tiger will eat 120 deer in a year; since there are 600 tigers, that means that the tigers will eat 72,000 deer a year. Supposing ten wolves eat a deer each day, the 500 wolves will eat up 18,000 deer a year. A newly born deer is not good at running; let ten foxes eat one young deer a day—during the period of a month when the young deer begin to run fast, the 10,000 foxes will eat 30,000 young deer a month. In all, the number of deer falling prey to these animals amounts to 1,200,000. The harm due from vultures, I have not counted. Thus seen, there will be no chance of obtaining them in large numbers. There is nothing like taking them early.”
Afterwards, Gao Rou's descendents would forever be hired as statisticians.
The Emperor and Cao Rui were once on a hunting party when they spied a doe and her young. The Emperor shot and killed the doe, and commanded Cao Rui to shoot the fawn. Cao Rui, with tears in his eyes, said, [4] "Your Majesty has already killed the mother, I cannot bear to kill the son as well." The Emperor, moved to compassion, threw down his bow and arrows.
I AM SUCH AN IDIOT
I just realized now that this was an allusion to the fact that Cao Pi killed Cao Rui's mother (Empress Zhao, nee Zhen aka "Zhen Ji") and Cao Rui is the "fawn." | 2023-08-09T01:26:28.774034 | https://example.com/article/8506 |
Q:
Javascript multiple circular graphs
Ive made a working circular graph using javascript, and Ive run into a problem.
The script fetches the id of the graph in order to work, but I would like multiple graphs.
So here is my question: How do I make the script compatible with multiple graphs? I tried fetching them by their class but that didnt seem to work.
Here is my code:
var el = document.getElementById('graph'); // get canvas
var options = {
percent: el.getAttribute('data-percent') || 25,
size: el.getAttribute('data-size') || 80,
lineWidth: el.getAttribute('data-line') || 5,
color: el.getAttribute('data-color') || 0,
rotate: el.getAttribute('data-rotate') || 0
}
var canvas = document.createElement('canvas');
var span = document.createElement('span');
span.textContent = options.percent + '%';
if (typeof(G_vmlCanvasManager) !== 'undefined') {
G_vmlCanvasManager.initElement(canvas);
}
var ctx = canvas.getContext('2d');
canvas.width = canvas.height = options.size;
el.appendChild(span);
el.appendChild(canvas);
ctx.translate(options.size / 2, options.size / 2); // change center
ctx.rotate((-1 / 2 + options.rotate / 180) * Math.PI); // rotate -90 deg
var radius = (options.size - options.lineWidth) / 2;
var drawCircle = function(color, lineWidth, percent) {
percent = Math.min(Math.max(0, percent || 1), 1);
ctx.beginPath();
ctx.arc(0, 0, radius, 0, Math.PI * 2 * percent, false);
ctx.strokeStyle = color;
ctx.lineCap = 'butt'; // butt, round or square
ctx.lineWidth = lineWidth
ctx.stroke();
};
drawCircle('#F7F7F7', options.lineWidth, 100 / 100);
drawCircle(options.color, options.lineWidth, options.percent / 100);
And this is the HTML:
<div class="chart" id="graph"
data-percent="92"
data-color="#1EA1FF"
data-size="110" data-line="3">
</div>
Thanks in advance.
A:
You should be able to surround everything with a loop. You need to select all the elements with the same class into an array, then loop through that array. I also suggest setting the "el" variable inside the array, then you don't have to change your code:
var graphs = document.getElementsByClassName("chart");
for(var i = 0; i < graphs.length; i++)
{
var el = graphs[i];
//Now the rest of your code
var options = ...
}
"el" then becomes each element as the loop iterates.
| 2024-05-17T01:26:28.774034 | https://example.com/article/5339 |
While some are out to exploit the face mask shortages plaguing areas of China amid the Wuhan coronavirus outbreak, others have promptly restored our faith in humanity.
Hao Jin worked last year at a mask factory. When he quit his job, the company couldn’t afford to pay his salary, so they compensated him with boxes upon boxes of face masks worth around 20,000 yuan ($2,900).
He brought those thousands of masks back to his home in a village near the city of Changde in Hunan province and pretty much forgot about them until he heard reports on the news about mask shortages brought on by the panic surrounding the deadly Wuhan virus.
Hao suddenly knew what to do with his mask stockpile. After keeping a few for himself and giving others out to his friends and family, he donated the rest, a donation of 18,000 masks.
“I don’t want anything else by donating,” he told the Xiaoxiang Morning Herald. “I just wanted to donate the masks so that can be of more use to people who need them.”
Hao has refused to accept any compensation, both from the public and from his local village committee. He has told netizens to not even bother contacting him. | 2024-04-09T01:26:28.774034 | https://example.com/article/9248 |
Background
==========
Metagenomics is a new scientific field that involves the analysis of organismal DNA sequences obtained directly from an environmental sample, enabling studies of microorganisms that are not easily cultured in a laboratory \[[@B1]\]. Metagenomic studies, pioneered in the early 2000s \[[@B2]\], have recently increased in number and scope due to the emergence of next generation sequencing technologies. Due to the difficulty of assembling entire organisms from a metagenomic dataset \[[@B1]\], most analyses take a gene-centric view, treating the community as an aggregate and ignoring the exact assignment of genes to individual organisms. In fact, it can be argued that the environment is better characterized by its gene complement rather than by its taxonomic composition, given that similar biological functions can be performed by microbes of distinct taxonomic origins. Supporting this view is the observation that, while the taxonomic composition of the human gut microbiome varies significantly between people, the functional profile is remarkably stable across samples \[[@B3]\]. The functional profile for a sample can be recovered by mapping sequences to gene families \[[@B4]\], subsystems \[[@B5]\] or metabolic pathways \[[@B6]\]. The relative abundance of each functional category can be estimated by counting how many sequences are assigned to each category, and this information is the basis for detailed comparisons of the functional potential of different functions. In a typical comparative metagenomics experiment, random shotgun sequences are generated from a collection of samples belonging to two groups, for example, obese or lean twins \[[@B3]\], and healthy infants or adults \[[@B7]\]. An important biological problem is to find differentially abundant functional signatures (e.g., genes or metabolic pathways) that are selected for by their local environments. Traditional analysis approaches compare the relative abundances of the categories one-at-a-time between different phenotypes, and compute the significance using one of several statistical approaches \[[@B8]-[@B10]\]. When comparing communities at the gene family level, many functional categories are commonly found to be differentially abundant, even after correcting for multiple hypothesis testing \[[@B3],[@B7]\]. The interpretation of these data can be daunting. An alternative approach focuses on functional subsystems and metabolic pathway comparisons \[[@B11]\], the number of which is much smaller than gene families. Results at these levels are easier to interpret and can provide a stronger evidence of distinct functional capacities than at the level of individual gene families. Such analyses, however, can be unnecessarily coarse. For example, the use of KEGG pathways as a basis for analysis is complicated by the following issues: (1) the definitions of pathways in KEGG are coercive, and the interactions between these pathways are ignored; (2) the genes in a pathway may not be fully covered by the identified genes in a metagenomic sample; (3) significant differences in the abundance of certain genes may be masked once the abundance of all genes in a pathway is aggregated.
To address these problems, we introduce a general method (MetaPath) for searching the global metabolic network to find differentially abundant finer-level subnetworks. For the purposes of this paper we define a subnetwork to be a connected set of genes that is statistically enriched or depleted in one group of samples. Underlying our approach is a statistical scoring system that captures the differential abundance for a given subnetwork, combined with a greedy search algorithm for a maximum weighted subgraph, to indentify the highest scoring subnetworks. Unlike previous approaches, MetaPath explicitly searches significant subnetwork in the global metabolic network (rather than the KEGG defined pathways), enabling us to detect subnetworks spanning predefined "containers". In addition, we developed rigorous statistical methods that take into account the topology of the network when testing the significance of the subnetworks.
Using simulated datasets, we demonstrate that Metapath outperforms previously described approaches for comparing biological networks based on abundance data. We show that our findings are more robust to noisy data than the results of single gene comparisons, and that MetaPath can find finer-level subnetwork than can be found by comparing predefined KEGG pathways. We also discuss the biological significance of the results derived from the application of MetaPath to actual metagenomic datasets, demonstrating that the output from MetaPath is easy to interpret and provides valuable biological insights. The software is freely available at <http://metapath.cbcb.umd.edu>.
Methods
=======
Datasets
--------
We tested our methods on two previously published metagenomic datasets, which were downloaded from the NCBI Trace Archive or Short Read Archive databases: (1) gut microbiomes from obese and lean twins \[[@B3]\]; (2) metagenomes from adult- and infant-type gut microbiomes \[[@B7]\]. Each dataset is divided into two populations of distinct phenotypes. The metabolic pathway data were downloaded from the KEGG pathways database \[[@B6]\]. The metabolic network is represented as a graph where nodes are metabolic substrates, and edges are molecular reactions (Fig. [1](#F1){ref-type="fig"}). The edges could be unidirectional or bidirectional depending on whether the corresponding reaction is reversible (as specified in KEGG database). Multiple reactions that are related to a same biological process are aggregated by KEGG into a "pathway" (e.g., glycolysis pathway). In addition, we refer to the network comprising all metabolic pathways in KEGG as the "global metabolic network". Metagenomic sequences are annotated through BLASTX searches against KEGG genes database. The abundance of each molecular reaction is estimated as the number of metagenomic sequences mapped to it. Note that more accurate abundance estimates can be obtained by taking into account the length of individual genes \[[@B12]\] and we plan to explore the use of such estimates (and the associated statistics) in future versions of our software.
![**Schematic diagram of the MetaPath methods**. Sequences from each sample are annotated against KEGG genes database and mapped to reactions in metabolic networks, resulting an abundance matrix where the rows are reactions and columns are samples. Then *p* values are computed for all reactions using Metastats \[[@B9]\], then converted into Z values, and greedy search is performed on the edge-weighted graph to find max-weight subnetworks. Finally, we calculate the p~abund~ and p~struct~ significance values of the max-weight subnetwork.](1753-6561-5-S2-S9-1){#F1}
Scoring metabolic subpathways
-----------------------------
To score the biological activity of a particular subnetwork, we first use Metastats \[[@B9]\] to calculate the significance of differential abundance for each reaction between the two phenotypic groups under comparison. Under the null hypothesis, the relative abundances are randomly drawn from the same distribution across different phenotypic groups, thus the *p* value for each feature (metabolic reactions) follows a uniform distribution from 0 to 1. Based on this assumption, *p* values can be converted to *Z* scores \[[@B13]\] using the Gaussian distribution. Because Metastats performs a two-tailed test for each reaction, the two-tailed *p* values can be converted back to the original *Z* values using the following equation:
where is the inverse cumulative density function (CDF) of standard normal distribution; G1 and G2 represent two different phenotypic groups. Using this formula, if a reaction is more abundant in population G1, then its *Z* score will be positive and vice versa. We are specifically interested in finding a pathway whose reactions are either enriched or depleted as a whole, as apposed to previous approaches \[[@B13],[@B14]\] that identify active or perturbed subnetworks, which may contain a mixture of enriched and depleted components. Similar to the approach of \[[@B13]\] we define the aggregate score for a particular subnetwork to be the sum of the *Z* scores over all reactions contained within it: , where *k* is the size (number of metabolic reactions) of the subnetwork.
Identifying high-scoring pathways
---------------------------------
As proposed in \[[@B13]\], we attempt to find subnetworks that maximize the cumulative Z- score defined above. Unfortunately, this problem is NP-hard, which is equivalent to finding a maximum-weight subgraph \[[@B13]\]. Several approaches to solving this problem have been previously proposed: Ideker, *et al.* 2002 \[[@B13]\] used simulated annealing, but this heuristic is slow; Dittrich, *et al*, 2008 \[[@B14]\] used integer linear programming that can find provably optimal subpathways quickly, but it requires the commercial software package CPLEX that is not available to the general public (using a freely available ILP solver would require re-implementing the entire algorithm as the software is provided as a binary-only release). Here we rely on a greedy search heuristic that is fast, and, while not guaranteed to find maximally scoring pathways, performs well in practice. The algorithm we employ is described below:
This algorithm tries to find a connected metabolic subnetwork, which can have any arbitrary structure, with maximum weight. However, it is believed that in metabolic networks, chains are especially more biologically meaningful and interesting, because they attempt to capture the structure of a series of reactions that are successively connected. To allow this idea, we modify line 8 of the above algorithm to "Pick an edge e~j~ which has the highest weight of the edges that are adjacent to and have the same direction with e~j-1~". Both searching algorithms are implemented in our program and can be selected through command-line parameters. To find all significant subnetworks (computing significance is discussed below), we iteratively remove the edges in the global network that are contained in previously found significant subnetworks, and rerun our greedy search on the rest of the network until we can no longer find any additional significant subnetworks. Note, that unlike the original version of our code \[[@B15]\], the search algorithm is not limited to given subnetwork size, rather will find all significant subnetworks irrespective of size.
Computing the significance of subnetwork
----------------------------------------
The null score distribution for a specific subnetwork can be estimated by permuting the sample labels (columns of the abundance matrix) of the reactions and computing the subnetwork scores from the permuted abundance matrix. The significance *p* value is estimated as the number of random permutations that produce higher scores than the original subnetwork. The *p* value computed through this approach (termed *p~abund~* throughout the rest of the paper), however, ignores the topology of the underlying global metabolic network, and potentially leads to incorrect conclusions. For example, assume we have a densely connected metabolic network, in which every edge is connected with all other edges. Then, the best subnetwork is simply composed of the top differentially abundant metabolic reactions. This indicates that whenever there are significant reactions, which may simply come from random noise given the large number of edges, they will form a significant subnetwork because of the biases from the network topology (Fig. [2](#F2){ref-type="fig"}). To address this problem, we compute another *p* value (termed *p~struct~*), relying on a topological definition of the null distribution of subnetwork scores. Specifically, instead of treating each subnetwork as a bag of genes, we estimate the distribution of scores for actual subnetworks identified within the underlying global metabolic network. Since this null-distribution depends on the size (number of edges) of the subnetwork, let *k* be the size of a subnetwork generated by the greedy search algorithm described above, and *Z* be the corresponding *Z*-score. The *p~struct~* value for this subnetwork can be calculated as follows: (i) permute the edge weights (row labels of the abundance matrix) of the global metabolic network; (ii) perform greedy search to find a maximal weighted subnetwork of size *k*; (iii) repeat step 1 and step 2 for 1000 times, and generate 1000 weights of the max-weight subnetwork (null distribution); (iv) the *p~struct~* value is the proportion of the 1000 times in step 3 that we see scores higher than our original observation *Z*.
{#F2}
MetaPath methods summary
------------------------
To summarize the methods described above, the MetaPath algorithm proceeds as follows:
1\. Differential abundance is assessed on an edge-by-edge basis (reaction-by-reaction) using Metastats;
2\. The significance estimates (*p*-values) from Metastats are fed into a greedy search algorithm to determine all maximally weighted subnetworks(in terms of statistical *Z*-scores) in the global metabolic network;
3\. The significance of each subnetwork detected by the greedy search algorithm is assessed using both a topology-independent bootstrapping approach (*p~abund~*), and a topology-dependent bootstrapping approach (*p~struct~*);
4\. The subnetworks determined to be significant (*p~abund~* ≤ *0.05* and *p~struct~* ≤ *0.05*) are reported to the user (Note: the threshold for significance can be adjusted through command-line parameters). The pathways are ranked by *p~abund~* values.
Results and discussions
=======================
Performance evaluation using simulated datasets
-----------------------------------------------
In order to validate our methods, we have designed a simulated metagenomic study and compared the results with three previous approaches: (i) identifying significantly active subnetworks using simulated annealing and greedy search \[[@B13]\]; (ii) discovering significant individual reactions using Metastats \[[@B9]\]; and (iii) finding differentially abundant KEGG defined pathways, an approach widely used in metagenomic functional comparison \[[@B3],[@B7],[@B10]\]. We choose these tools because they are addressing similar biological problems. However they do not solve the exact same problem as this paper, which is finding differentially abundant subnetworks that may span two or more KEGG defined pathways (see discussion in the Background section). Here the goal of this simulated study is to show that the computational problem in this paper can not be directly solved by applying methods previously developed in a related context.
We designed a simulated metabolic pathways dataset in which five subjects are created for each of the two groups with distinct phenotypes. To generate the artificial reaction abundance matrix (where rows represent reactions and columns represent subjects), a Gaussian distribution is created for each reaction, whose mean is randomly chosen from a real metagenomic dataset (gut microbiome from obese and lean subjects \[[@B3]\]). The variance of each distribution is calculated by setting the relative standard deviation (standard deviation divided by the mean) to 0.2. If we define a reaction to be equally abundant between two groups under comparison, then a random abundance value is generated from the same distribution for each subject. Otherwise, if a reaction is defined to be significantly enriched in one group, then another normal distribution is created for this reaction by increasing the mean such that the *p* value of the difference for the two distributions is less than a predefined value (0.05 and 0.01 were used). In this study, we have chosen a subnetwork (a series of reactions with length 5 or 10) to be enriched in one population. The goal is to compare different methods in recovering this significant subnetwork (a set of significant reactions) based on the simulated abundance matrix. Biologically, the enriched pathways indicate functional enrichment of certain biological processes in a microbial community.
The receiver operating characteristic (ROC) curve is plotted for each method (Fig. [3](#F3){ref-type="fig"}). Fig. [3](#F3){ref-type="fig"} shows that MetaPath outperforms all other methods dramatically showing the advantage in finding significant subnetworks. Note that the results tested on our simulated datasets can be considered as the baseline performance, because it contains only one significant subnetwork, whereas real metagenomic datasets typically contain multiple significant pathways. The most commonly used approach --- comparing KEGG-defined pathways --- performs the worst in our simulation study (Fig. [3](#F3){ref-type="fig"}).
![**Comparison of statistical methods for discovering significant reactions in simulated datasets**. Four methods are evaluated: discovering active subnetworks using simulated annealing (Anneal) and greedy search (Greedy) \[[@B13]\], discovering significant individual reactions using Metastats \[[@B9]\], finding differentially abundant KEGGdefined pathways (KEGGPath), and MetaPath. Four datasets are created by varying the number of significant reactions *n* and their significances.](1753-6561-5-S2-S9-3){#F3}
Obese and lean twins
--------------------
We used MetaPath to compare the abundances of the metabolic networks of the gut microbiome in lean and obese subjects, relying on data from \[[@B3]\]. This metagenomic dataset comprises 6 samples from obese subjects and 6 samples from lean objects. The sequences are annotated and mapped to KEGG reactions using BLASTX (E value \< 10^-5^, bitscore \> 50, and %identity \> 50; parameters suggested in the original study), resulting in total 1832 unique reactions within the 12 metagenomic samples. First, we computed *p* values \[[@B16]\] using Metastats to find differentially abundant reactions. Using a *p* value cutoff of 0.05, 92.7±9.1 (mean±standard deviation) reactions are significant including 37.1±6.6 and 55.6±3.1 enriched reactions in obese and lean groups, respectively, based on 10 runs of Metastats. The high variance of the number of significant genes can be primarily explained by two reasons: (1) some reactions are slightly below or above significance cutoff (0.05), thus *p* values computed through bootstrapping will jump between being considered significant and not significant (Fig. [4](#F4){ref-type="fig"}); (2) there are large variances of the abundance values within individuals in a same phenotypic group. In addition to *p* values, Metastats also provides an estimate of the False Discovery Rate (*q* value), information that is not used by MetaPath. The *q* values for all reactions are 1 (except R01676 where *q*=0.73), i.e. a literal interpretation of Metastats results would indicate no pathways are significantly different between the two populations. This result can be explained by the flat distribution of the *p* values (Fig. [4](#F4){ref-type="fig"}), from which the *q* values are estimated. This observation highlights the limitation of relying on the false discovery rate, which requires the estimation of the proportion of features that are truly null \[[@B16]\], approach that does not perform well when only few features are truly significant.
{#F4}
We, then, applied MetaPath to this dataset, and have found 9 differentially abundant subnetwork (Fig. [5](#F5){ref-type="fig"}) using 0.05 cutoff value for both *p~abund~* and *p~struct~*. All these subnetworks are enriched in obese subjects; none was found to be enriched in lean subjects. These 9 significant subnetworks contain 48 unique reactions, 22 of which are significant. It is worth pointing out that the number of significant reactions varies between different runs of statistical permutations (using Metastats) as shown above, but the significant pathways identified by Metapath stay the same (Fig. [5](#F5){ref-type="fig"}). This observation confirms that the results from MetaPath are more robust in the presence of noise in the data than the gene-by-gene approach. In the *p* values distribution of subnetworks (Fig. [4](#F4){ref-type="fig"}), most of them are either very significant or insignificant and very few are around the *p* value cutoff, allowing the users to easily interpret the results.
{#F5}
Five subnetworks (Fig. [5a-5e](#F5){ref-type="fig"}) are completely contained in the KEGG Fatty Acid Biosynthesis pathway, which consists of catabolic processes that can generate energy and primary metabolites from fatty acids. Our findings are consistent with previous observations and biochemical analysis in microbiota transplantation experiments in germ-free mice \[[@B17]\], where the concentrations of short-chain fatty acids in the caeca of obese mice are higher than lean mice, suggesting that the gut microbiome in obese subjects has an increased capacity for dietary energy harvest.
Another interesting significant networks consists of 10 reactions (Fig. [5f](#F5){ref-type="fig"}), of which 8 belong to Cysteine and Methionine Metabolism and 2 belong to Sulfur Metabolism. Many reactions in this subnetwork are connected by the L-Homocysteine molecule. In addition, three other subnetworks (Fig. [5g-5i](#F5){ref-type="fig"}) we discovered further confirm its potential involvement in obesity, because all these three pathways contain L-homocysteine as metabolite. It is well-known that a high level of blood serum homocysteine is a risk factor for cardiovascular disease \[[@B18]\], and obesity --- an increasingly prevalent metabolic disorder --- is closely associated with heart disease \[[@B19]\]. Significant correlations between plasma homocysteine concentrations and obesity have been previously reported \[[@B18],[@B20]-[@B23]\]. The finding of increased potential for homocysteine metabolism within the obese gut microbiome provides an interesting hypothesis for future studies that, the gut microbiome may either have a direct role in the elevation of homocysteine levels in plasma, or may indirectly affect the hepatic biosynthesis of this amino-acid in the human body.
Infant and adult individuals
----------------------------
A second data-set comprises gut microbiome samples from 4 infants and 9 adults individuals which were sequenced by Kurokawa, *et al*., 2007 \[[@B7]\]. The sequences were annotated and mapped to the reactions of KEGG pathway using BLASTX (E value \< 10^-8^, hit length coverage ≥ 50% of a query sequence), resulting in total 1781 unique reactions within the 13 metagenomic samples. Based on 10 runs of Metastats, 383.7±1.56 reactions are significant using *p* value cutoff of 0.05, including 268.7±1.56 and 115±0 reactions enriched in infant and adult subjects respectively.Using a *q* value cutoff of 0.05, 167.2±2.7 reactions are significant, including 133.2±2.7 and 34±0 reactions enriched in infant and adult subjects respectively.Compared with the previous dataset (obese and lean twins samples), the predictions of significant reactions are much more consistent across different permutations.
Applying MetaPath to search for significant subnetworks using the same parameters as before, we have found that 6 are enriched in infant subjects (Fig. [6a-6f](#F6){ref-type="fig"}) and 4 are enriched in adult subjects (Fig. [6g-6j](#F6){ref-type="fig"}). These 10 significant subnetworks contain 55 unique reactions (35 and 20 in subnetworks enriched in infant and adult, respectively), including 38 significant reactions (22 and 16 enriched in infant and adult, respectively) and 17 reactions not found significant by Metastats. Three subnetworks enriched in infant subjects (Fig. [6a, 6c and 6d](#F6){ref-type="fig"}) involve the metabolite L-homocysteine, and a fourth one (Fig. [6b](#F6){ref-type="fig"}) involves L-cysteine -- a related amino-acid, which is consistent with previous observation that breastfed babies have an higher plasma homocysteine level possibly caused by suboptimal availability of folate in breast milk \[[@B24]\]. The concentration of folate is negatively correlated with that of homocysteine, as folate is a necessary coenzyme for reactions that metabolize homocysteine. In addition, babies normally have high protein diet, which may also cause the concentration of homocysteine to increase. A second pathway in Fig. [6e](#F6){ref-type="fig"} involves substrates citrate and succinate, and is closely related with oxidative tricarboxylic acid (TCA) cycle. TCA cycle is part of carbohydrate metabolism and can convert carbohydrates into usable energy in aerobic organisms. Because the adult gut ecosystem is dominated by strict anaerobes, it is reasonable to find this subpathway enriched in infant individuals where the gut microbiota also includes aerobes. This finding is consistent with results obtained by comparing COG functional categories \[[@B7]\]. We also find a subpathway belonging to atrazine metabolism to be enriched in infant subjects (Fig. [6f](#F6){ref-type="fig"}). Atrazine is one of the most widely used herbicides, and it contaminates water and soil throughout the world. Our finding possibly indicates a side-effect of this contamination.
{#F6}
The pathway in Fig. [6i](#F6){ref-type="fig"} (enriched in adult subjects) is part of the lipopolysaccharide biosynthesis. Lipopolysaccharides are a building block of the outer membrane of Gram-negative bacteria. The enrichment of pathway Fig. [6i](#F6){ref-type="fig"} in adult subject may be a result of the fact that Gram-negative bacteria are also enriched in adults. Specifically, Bacteroides, a genus of Gram-negative bacteria, are a major constituent of adult gut microbiome, but not highly prevalent in infants. Fig. [6h](#F6){ref-type="fig"} and Fig. [6j](#F6){ref-type="fig"} (enriched in adult) are pathways related with pyrimidine metabolism. The metabolites RNA, cytidine and uridine, which are contained in pyrimidine metabolism, are normally obtained from high RNA food such as organ meats, broccoli, and brewer's yeast, which are not available to unweaned infants, as they are not present in high abundance in milk. The pathway in Fig. [6g](#F6){ref-type="fig"} (enriched in adult) is part of fructose and mannose metabolism a pathway related to carbohydrate metabolism. This is also consistent with COG-based analyses indicating that many mono- or disaccharides metabolism genes are enriched in adults \[[@B7]\], explained by the fact that colonic microbiota in adults uses indigestible polysaccharides as resources for energy production and biosynthesis of cellular components.
Conclusions
===========
We have introduced a statistical method for finding significant metabolic subpathways from metagenomic datasets. Compared with previous methods, results from MetaPath are more robust to noise in the data, and have significantly higher sensitivity and specificity (when tested on simulated datasets). When applied to two publicly available metagenomic data-sets the output of MetaPath is consistent with previous observations and also provides several new insights into the metabolic activity of the gut microbiome. Finally, MetaPath is efficient: a typical metagenomic dataset and the corresponding metabolic network (about 2000 edges) can be analyzed in half an hour on a single processor.
While showing promising results, our methods have several limitations that we plan to address in the near future. First, and foremost, we restrict ourselves to pathways of a fixed length --- a restriction necessary for accurately computing the null distribution of pathway scores. This can severely affect our ability to discover long pathways whose abundance differs only slightly, but significantly, between samples. Second, we currently estimate gene abundances by simply counting the number of sequencing reads that map to a certain gene. Such an approach ignores differences in the length of genes, potentially leading to incorrect conclusions. We plan to address this issue by incorporating a recently-published \[[@B12]\] method that can accurately correct for gene-length effects. The software described in this paper is freely-available under an open-source license from <http://metapath.cbcb.umd.edu>
Competing interests
===================
The authors declare that they have no competing interests
Authors\' contributions
=======================
BL and MP conceived the project, designed the algorithm and wrote the manuscript. BL implemented the algorithm and analyzed the data. Both authors read and approved the final manuscript.
Acknowledgements
================
We thank Niranjan Nagarajan, Carl Kingsford, James White and Saket Navlakha, Theodore Gibbons for helpful discussions. This work was supported in part by grants R01-HG004885 from the NIH, and IIS-0812111 from the NSF, both to MP.
This article has been published as part of *BMC Proceedings* Volume 5 Supplement 2, 2011: Proceedings of the 6th International Symposium on Bioinformatics Research and Applications (ISBRA\'10). The full contents of the supplement are available online at <http://www.biomedcentral.com/1753-6561/5?issue=S2>.
| 2023-10-12T01:26:28.774034 | https://example.com/article/8452 |
May 24, 2013
The spreading and deepening discontent with Egypt's President Mohamed Morsi and the Muslim Brotherhood government he leads has found a new expression: the Tamarrud (which means "Rebellion") campaign to gather 15 million signatures in support of a document that expresses the Egyptian people's lack of confidence in the new regime and that calls for an early presidential election. Here, the Revolutionary Socialists of Egypt explain the petition campaign's importance in the context of the current situation, more than two years after the uprising that toppled dictator Hosni Mubarak in February 2011.
SINCE ITS inception on January 25, 2011, the Egyptian Revolution has seen many twists and turns in its path.
We have sometimes seen great ascents in the revolutionary movement, with not just hundreds of thousands, but millions taking to the streets and the squares against Hosni Mubarak, the Military Council and, after them, Morsi in support of the demands of the revolution and their implementation. The rising of the populace for democratic demands has usually accompanied or followed a rise in the social movement, from workers' strikes and protests demanding bread, social justice and improvements in working conditions; to the overthrow of the corrupt administrations.
Other times, we have seen the partial retreat of the revolutionary movement, a dispersal of the ranks of the people and the revolutionary vanguard, a widespread frustration that leads some to believe that the revolution has ended. These times especially are the periods when the attacks of the counterrevolution increase, to push back any gains the people have achieved at the high water marks and to bolster the institutions of the ruling class and strengthen them in anticipation of the next revolutionary wave.
Protesters march through Cairo streets marking the second anniversary of the beginning of the revolution
Under the shadow of current conditions, with an uptick in popular discontent against the rule of the Muslim Brotherhood and their ruling class associates from the army, police and business elite, there has been an increase in frustration and despair of any change. But now, the Tamarrud (Rebellion) Campaign has been launched by a group of revolutionary youth, with the idea of collecting 15 million signatures within two months across all the governorates for a document expressing no confidence in Morsi and calling for an early presidential election.
THIS CAMPAIGN has succeeded within a short time in spurring great momentum in the streets and in the political field more generally. The campaign has been active in neighborhoods across the governorates, and has succeeded in collecting more than 2 million signatures in 10 days [Update: now more than 3 million]. It has brought to many of the frustrated revolutionary youth renewed energy and hope, reviving once again popular political discussion. It has become a channel into which the burgeoning popular indignation at Morsi's presidency can flow in light of the clear decrease in demonstrations and protests in the squares.
You must target your efforts at these millions of embittered people, go out to meet them, discuss with them and call upon them to make efforts toward change, not to wait in frustration. Raise slogans challenging the current powers and say: "If you think the president is not achieving what we wished of him, if you think that he doesn't represent what you wish to see achieved, then don't wait three more years to change him--we'll change him now...because we the people have decided to do so."
The sense of disillusionment in what was chosen by the ballot box was felt spontaneously by progressive segments of the people, who became aware of it in their daily lives and political lives and through the speeches of the Muslim Brotherhood leaders. This growing awareness imposes upon every revolutionary fighter the necessity of working to develop popular democratic alternatives which express the desire of the people. By organizing themselves in new ways, they can express their wish for something other than the status quo, which has never and will never represent anything other than the same politics that we came out to rebel against in our revolution.
The tactic of collecting popular signatures to pressure those in power has been used previously, both recently and historically. We might recall the campaign of collecting signatures for a change in the National Assembly a year before the revolution, and the campaign of collecting signatures for renationalizing the privatized companies and for a minimum and maximum wage more recently. In those situations, the campaigns stirred the stagnant waters in extreme periods, helping to raise the consciousness of the masses to take steps forward.
We in the Revolutionary Socialist Movement understand the limitations of this type of campaign, for it cannot, of course, topple any regime on its own. For without a broad mass movement led by members of the working class, the basic pillars of the regime and the state cannot be shaken. However, we recognize that this moment anticipates a long path of democratic and social struggles necessary for mass consciousness--uneven by definition--to ferment. These struggles serve to increase the confidence of the masses in themselves and in their power to create change.
For this reason, it is necessary for us as a fighting Marxist revolutionary movement to support this democratic campaign, which works toward building mass consciousness from below. We must build this campaign and engage with it where it is effective and open our headquarters to it, so that our mission and our huge responsibility is to be a vehicle for it.
It is incumbent upon us to get out into the streets and into every corner of every neighborhood, factory and organization. We should not only collect signatures for the petition--which is important in its own right--but also facilitate broader discussions with people in these places, always making connections to the social struggles and showing the connections between the policies of the current government and the difficulties of the people in their daily lives.
This is also an important opportunity for us as revolutionary socialists to connect with hundreds of revolutionary youth involved in the campaign, to share our views with them and to understand their viewpoints. But not only that, it is an opportunity for us to engage with broad segments of the country in different governorates--to conduct discussions about the feasibility of withdrawing confidence in the "elected" president, and to extend the discussions to the broadest possible revolutionary horizons.
AS FOR the National Salvation Front (NSF), we rejected participation in it because of its previous association with the remnants of the old regime and because it distorted the revolutionary consciousness of the people, mixing the corrupt soil with the fertile. Soon after, as experience has shown us, it failed. It continues to be unable to put forth any fundamental alternative or any revolutionary agitation that would put it in the forefront of a broad democratic movement to overthrow the current regime.
Not only that, but the NSF has been content to remain on the sideline of the struggle, apologizing every time it is compelled to mobilize the masses for the narrowest possible rights. The NSF wants no more than a preferred seat at the table to negotiate with the reigning dictatorial powers, in order to share in political positions in the government and parliament. This goal is the highest goal that it can accomplish. It is exactly this performance that has disappointed the hopes of broad swaths of the public.
What is completely new and different about the Rebellion Campaign is that it stems from a popular initiative, opening up space for revolutionary work and experience from below. Beyond that, the theoretical and practical possibilities of beginning a grassroots opposition movement far exceeds the narrow opportunist horizons of the leadership of the National Salvation Front. The campaign utterly opposes the projects of the old regime remnants, which loathe democracy many times more than they hate the Muslim Brotherhood.
This strategy relies fundamentally on the conscious and unified intervention of the vanguard of revolutionaries in this struggle, to win them over to a viewpoint that uses this campaign as a lever. The revolutionary leadership must organize the political struggle of the masses to a level of preparation for the coming confrontation with this tyrannical regime.
Our movement cannot trail in a struggle like this one and cannot forfeit an opportunity to develop the consciousness of different sectors of the popular revolutionary masses. This is an opportunity to restore confidence in the power that connects and drives the people collectively against the police state. Therefore, we announce our full and determined participation in this campaign and call all those struggling for democracy and justice to participate with us and with the entire working class movement in carrying out this battle. This can only lead the way sooner or later to a second popular uprising against this dictatorial regime with all of its interests and biases, to raise in its place the authority of the rule of the many in the interests of the many.
Long live the glorious revolution of freedom!
The Revolutionary Socialists
May 19, 2013
Translation by Jess Martin | 2024-01-07T01:26:28.774034 | https://example.com/article/3881 |
Features
This product really came in handy. I somehow lost the toe stop on my left skate. I orderd a new pair from Sun and Ski . Stop works perfectly and has not come loose. Thanks a lot! You saved me from having to use the horrible rink skates at derby practice!
Was this review helpful to you?
Ask A Question
100% Performance & Price Guarantee
We want you love your gear like we love ours. 100% Performance Guarantee - Every Item, All of the Time | 2024-07-28T01:26:28.774034 | https://example.com/article/7226 |
Antares 20E
The Antares sailplane-family’s history began with our Antares 20E. Antares is an entirely new development. With its innovative ideas and a revolutionary propulsion concept it stands for what is currently achievable in sailplane construction. | 2023-09-19T01:26:28.774034 | https://example.com/article/8967 |
I had no idea he was so knowledgeable about technology. I thought he & Richard Sanders, another Babbler, would enjoy meeting - they're in the same neck of the woods, & both very accomplished pro-peace activists.
But, I can't find a way to search the forum. When I search, I get Rabble articles, but I want to find forum threads.
The only search capability on babble is the tiny box in the upper right corner of this screen. It retrieves both rabble and babble items without discrimination. The babble items are limited to threads that have been migrated from the old site, although I have found many such threads that are invisible to the search engine. There is no Advanced Search option. In short, forget it. All that database of six years' worth of discussion, links, and useful information is gone from the web, probably forever, but at least for a very long time.
Perhaps you were hoping I had stopped using an annoying tag line. You were wrong; you're reading it now. Why not email a moderator to demand that signature/tag lines be abolished forthwith?
I have uncovered a ton of details on Freeland's Nazi propagandist grandfather and have posted it to the "news by the rest of us" forum but it is not going through, at least I can't see it there or anywhere. Babble tells me the new topic has been created but also calls my post "unpublished". What gives?
Can somebody please help. btw you can use google to search contents of websites...
Babble isn't very functional these days. I opened a new thread a couple of days ago, and it did appear within a few hours. So there's hope for your thread. And more information on Freeland will be very welcome.
Thanks Unionist, I'm so glad to hear it isn't just me. I posted it three times so I guess if any of them show up I can delete as appropriate. Two other odd things. I can't seem to send personal messages anymore and in the listing of forum topics it doesn't mention anymore how many views particular articles have had, which i found useful.
Himka's papers are definitely worth reading, as they provide good background on the role played by Krakivisti Visti ( it was not a local paper, and it was not distributed in Ukraine; it was for Ukrainian-speaking workers throughout occupied territories). Also, he points that collaboration was not so simple. Publishing in Nazi-controlled areas meant that Ukrainian nationalists were able to report on atrocities taking place in the Soviet-occupied zone that would not have been possible on the other side of the line.
And while Himka (who is Freeland's uncle) is indeed responsible for the articles he wrote, he pointed out in the Globe and Mail that Freeland helped with clarifications and corrections regarding their family.
I do agree that Freeland missed an opportunity, even if accusations of her lying and denying are false. Her statement about propaganda would have done better if she was more specific about what she was talking about.
This Bloomberg article cuts through the dilemma nicely. There is also a link in there to another of Himka's papers detailing how complicated the collaboration between Ukrainians and Nazis was. I strongly recommend reading it.
Thanks, NDPP, I worked on the Freeland Chomiak connection full-time for the past 8 weeks. It has consumed me.
I found a lot of info that no one else has written about, especially about Freeland's early journalism career with ultraright Ukrainian media BEFORE her journalism career is said to have even started (according to her own deceptive narrative)
The material I posted to the COAT site is just the tip of the iceberg. I have numerous other articles written.
But I can't post any of it to Babble. I can send comments but am not able to post anything. Yet others are doing it. Why can some people post and others cannot?
One think I find truly amazing is how no matter what the subject certain people alwayys find a way to spin the discussion into a slam against the Russians. It's incredible. There was a day when certain people could turn every conversation into a slam against Jews (and Russians or Soviets) but those days are largely past. Now, Russians and commies are still fair game for slamming and it done by people on the far right and the NDP, which on anticommunist/antiRussian front are pretty much the same.
But imagine turning a discussion of the Holocaust into a slam against Jews. Unthinkable right?
But the Soviets lost 25-30 million in WWII including almost 9 million troops fighting the Nazis and yet certain people have the chutzpah to turn a reference to the Nazis into an oppportunity to slam the Russians. Incredible guts and gall. Someday people will look back on such discussions the same way we look at the antiSemitism that was so rampant in certain cirlces, like business, government, churches, mainstream society.
Anyhow if there is anyone out there that has a clue as to how to get through the Great Wall of Babble, I'd appreciate. | 2023-09-14T01:26:28.774034 | https://example.com/article/2673 |
CLEMSON – Up off the deck. Back from the dead. Nail in the coffin. Turn out the lights. Digging yourself out of a hole. Name the cliché that describes a miraculous comeback, and it fits what the Clemson baseball team accomplished Saturday afternoon.
But those tired clichés don’t even begin to describe the emotion felt by the coaches, players and the faithful fans that remained inside of Doug Kingsmore Stadium. Jay BaumJay BaumJr. Infielder#13 6-0, 190Alpharetta, GAView Full Profile’s laser double to right-center field scored Garrett BoulwareGarrett BoulwareJr. Catcher#30 6-1, 210Anderson, SCView Full Profile from first base – Boulware later said it was the fastest he’s ever rounded the bases in his life – setting off a celebration worthy of a Super Regional win as the Tigers defeated Boston College 10-9 in 13 innings.
It wasn’t a Super Regional, but the win gave the Tigers a No. 5 seed in next week’s ACC Tournament, and only helped Clemson’s NCAA Tournament chances. A loss would have almost certainly have killed those tournament chances, and Clemson would have entered the ACC tourney as losers of 12 of their last 17 ACC games, including going 2-4 against ACC cellar dwellers Notre Dame and Boston College.
Instead, they have a new outlook and a little bit of confidence heading into the homestretch. The Tigers trailed by seven runs in the seventh, they were down five going to the ninth, down four with one out left and down three while down to their last strike on multiple pitches.
The early deficits were a reflection of the lead gray skies and chilly conditions, the kind of depressing afternoon that seemed to be a microcosm of a depressing season. Fans left in droves, and those that stayed were wanting, praying and aching for something good to happen.
It did. Jon McGibbonJon McGibbonSr. 1st Base#12 6-1, 220Lindenhurst, NYView Full Profile came delivered a 3-run double that tied the score in the ninth, and Baum’s double scored Boulware with the running run. What was once an emotionless stadium, the winds of hope instead blowing in clouds of despair, were at once replaced by a little bit of sunshine.
Embattled head coach Jack LeggettJack LeggettBaseball Head CoachView Full Profile, looking as old and haggard as I’ve ever seen him, could only shake his head at first.
“It shows the character of this team and that they are never going to give up,” said Leggett. “Our guys battled. We scored five runs and four with two outs in the ninth inning. Jon McGibbon came up with a huge hit to clear the bases and tie the score. Matt CampbellMatt CampbellSr. RH Pitcher#36 5-11, 195Alpharetta, GAView Full Profile came in and pitched his heart out. A lot of good things happened today, and I am proud of how our kids battled and how tough they were.”
Leggett said that he was almost willing Boulware around the bases.
“I almost beat him to home plate,” Leggett said. “I had him attached to my hip, I think. (Boulware) just happened to be in the right spot. There were two outs. He was on the move. As soon as it was hit, I was thinking this is going to be close so I was gaging it before he got to second base and then he cut the ball off with his backhand side and I was hoping he would bobble it once or something, but he caught it cleanly.”
Reliever Matt Campbell – who usually pitches two innings – had already pitched five strong innings in collecting career highs in pitches (84) and innings (5). With Campbell facing a sixth inning, Boulware said he was thinking about his teammate during his romp around the bases.
“He has not thrown that in four years,” Boulware said. “It was the bottom of the 13th or whatever it was and I was like, ‘I have to score this run.’ I knew we had other guys in the pen but he was on lockdown and we did not need to push him any further.”
Because of McGibbon’s heroics, Campbell’s stellar work and Boulware’s speed in crunch time the Tigers will be the fifth-seed in next week’s ACC Tournament in Greensboro, N.C., and avoided having to play in the play-in game on Tuesday.
That also meant the Tigers might make the NCAA Tournament field and avoid staying home for just the second time in 28 years, something that Leggett said he was fully aware of.
“It could have been. It could have been,” Leggett said. “That’s all there is to it. You don’t want to get in the play-in game. You want to get to Wednesday and we needed to especially with the pitchers we used up today. If we had to play on Tuesday, it would have been a tough challenge for us. So who knows how it will pan out at the end? We have to go to the ACC Tournament and do some good things.” | 2024-05-18T01:26:28.774034 | https://example.com/article/8689 |
Just For Today
Dear Readers,Lately I have found myself feeling left out, about not being part of an “in-group”.I often feel very insecure when it comes to people. I will say something and then worry I said the wrong thing, or I talk too loud, and someone tells me to be quieter.I often don’t hear things people say in a group situation and so I either have to ask people to repeat, which gets old after a while for them, or I pretend I know what’s going on, which leads to strange conversations. Sometimes I give up and leave.I often want to be part of the “in-group” so much, that I forget to be happy with what gifts I already have!
Slowly but surely, I am learning that the secret to life for me, is being grateful. A woman I know, commented on the fact that Mr. UT is a wonderful guy.I told her, I did not really appreciate him and all that he does for me, until I got sober.
Sobriety, (as Anne of Ainsobriety often says), is a gift.It keeps bringing me new ‘aha” moments. It gives me the chance to step back when I am upset or sad, and ask myself some questions, and then to be open to the answers.
And because I have lately had the feelings of being left out, I asked myself, “Why is it important to me to be included with these people?”“What do I need or want that I am not getting?”The answers that came to me were that I need and want connections, love and approval.When I look at what I already have, and I discover that I have connections, love and approval right now.I do not need to seek these things.Instead, I want to appreciate the people that love me unconditionally.This is a gift sobriety brings.
So, just for today, I will be sober, grateful, and probably a little loud!With Love,On 35 Months and 3 Days,WendyPS – It was my birthday last Tuesday, and Mr. UT bought me a beautiful dress, and even got the right size!!
Post navigation
41 thoughts on “Just For Today”
Hi Wendy,Congratulations on your birthday! Looking GOOOOD! 🙂 Very, very nice.I am sorry to hear that your hearing problems make it difficult to follow (group) conversations. I do not like groups very much. Have difficulty dealing. Might sound as a luxury problem in comparison. I just get lost in the group and afterwards am very tired and disconnected with myself. That is why I tend to not meet with more than 1 or 2 people at the same time. Just to keep close to myself. I need that because for me, wanting to be part of that group somehow reminds me of drinking. I sometimes feel that even while I drank water or tea all night, I am drunk. Not sure how that works. Hmmm, that would be a subject to think about.Not sure if you (still?) need it but I think I am speaking truth when I say you are one of the most loved bloggers in this sober community. Your kindness, your gentleness, your loving pressence is something I can only hope to be able to express myself one day. That trajectory is long, very long but thank you for writing, thank you for showing me this. <3xx, Feeling
Wendy, happy birthday, nice dress and forget those other groups, you are a member of this blogging community. Now that's a real in-crowd! As the previous person suggested you are one of the most open minded, compassionate and supportive bloggers I have encountered. Keep it going.Jim
What a gorgeous dress and gorgeous you!Happy birthday.I often feel I have more love and interest in the people's lives I only know through blogging. I don't have a lot of close friends. I don't really want to put the time in.But what I do love are short, intimate contacts. A chat after yoga about someone's struggles or success is often more intense and rewarding than most of my old friendships.I find like being alone. But, It must be isolating to not hear. I felt isolated in Quebec when everyone spoke French and I did not. I felt self conscious and left out. Maybe that's a bit how you feel and I'm sorry. It makes me wonder if there are people who have hearing loss who don't come to yoga because of that. You are brave and inspiring to keep trying!Your blog opens my eyes to many things….your comments are always heartfelt. It is an honour to walk this path with you…Your friend,Anne
Those kind words from others, up above…? Double ditto! What you share in your entries here and your posts on other blogs do radiate kindness, generosity, encouragement and sensitivity. Belated birthday greetings to the pretty lafy in the pretty dress!
As Feeling says – your warmth and reaching out to other bloggers in this community is a beacon of hope to so many. if you are using that (very real and understandable) pain of sometimes feeling isolated due to your hearing difficulties and turning it into something beautiful, then that is something to be very proud of. and your appreciation of Mr U-T is a beautiful thing, too. much love from England! Prim xxPS – excited to see that you are nearly at 3 years! hope you share your celebrations with us!
Happy Birthday Wendy!You offered me hope when I had none,You encouraged me when I thought I was done.Your honesty comes from your heart,It gives others the courage to start.Through your sober journey you have shown,That if we have the bravery to begin we are never alone.thanks Wendy!Michelle xxx
Hi Wendy, I was feeling this way earlier in the year and decided to focus on my actual friends. I wrote down my list of good friends and now just focus on those. If I feel left out of something and the people involved are not on my list I let it go. I don't worry what they are doing and put no effort into becoming friends with them, other than being polite. It's helped me a lot and also made me redirection my focus on those who matter to me the most. Love your dress by the way and happy birthday!
Wendy you are rocking that dress! I can very much relate to the wanting to fit in. I am glad you are noticing the places in your life where you already do, like here in sober blogging world. You are awesome:) xxx
I am so with you on groups, Feeling- too many personalities at one time drain me. I think the disconnectedness we feel might come from just trying so hard to follow along. Sensory overload. Some re-charge by being with people- I need to re-charge with solitude.
Thank you, Anne. Your wise words touch so many people here!In the yoga studio, I hear about 50% of the words spoken, but I just follow along for the ones I don't hear or understand. Music makes it much worse. But you are so right…I don't like big groups anymore. I like one on one times the most!xo
You look lovely in your birthday dress! I hope you had a great day. I've also struggled my whole life with wanting to fit in but never feeling like I have. I also prefer very small social groups now and have developed an appreciation of alone time. I think quality not quanitity is definitely a thing with friendships. I agree with earlier comments here, you're definitely popular and loved in this community. Hugs x
Ohhh I LOVE your new dress!! It's beautiful! And so are you! Happy belated birthday Wendy!!So many people above have already said the things that I would like to say too. I am very, VERY thankful and grateful that you are part of our \”group\”. I only have a few friends in real life, and I have felt more welcomed and listened to on this online community than I think I ever have, and you have been a HUGE part of that for me. <3Donna
Thank you, TOTW!It helps I don't have to hear here! ha ha!After writing this post, I immediately felt better.I realize I had to look at what I have and take care of that.I am happy to be alone as long as I get some close friend social time a few times a week!xo
I'm so sorry I'm late!! But You ARE looking really great in that dress! Your man has a good eye! I also get it – wanting to be part of…but I gotta agree with Mark. You ARE the in-crowd! You're one of my most beloved bloggers here in the Recovery Posse. Xoxo
Happy Belated Birthday! You look marvelous in your gift, husband made a wonderful choice. You truly are appreciated and respected in this blogging world. I believe in your outside life as well. Thank you for being you! | 2023-12-18T01:26:28.774034 | https://example.com/article/7047 |
32 Ill. App.3d 682 (1975)
336 N.E.2d 281
THE PEOPLE OF THE STATE OF ILLINOIS, Plaintiff-Appellee,
v.
WILLIE J. DREW, Defendant-Appellant.
No. 12646.
Illinois Appellate Court Fourth District.
October 10, 1975.
Richard J. Wilson, Joshua Sachs, and Daniel D. Yuhas, all of State Appellate Defender's Office, of Springfield, for appellant.
*683 C. Joseph Cavanagh, State's Attorney, of Springfield (G. Michael Prall and Kai A. Wallis, both of Illinois State's Attorneys Association, of counsel), for the People.
Vacated in part, affirmed in part and remanded.
Mr. JUSTICE CRAVEN delivered the opinion of the court:
A jury found defendant guilty of robbery and armed robbery, and sentence of 10 to 30 years' imprisonment was imposed. Defendant appeals, contending that entry of judgment on the robbery verdict was erroneous and that the sentence imposed was excessive.
The record shows that the defendant and five other persons were heading north on Interstate 55 during the early morning hours of April 28, 1973. Near Litchfield, Illinois, they picked up two hitchhikers. Some time later, the automobile developed mechanical problems and they stopped at a service station. The two hitchhikers testified the station was well lit and they were able to see all other persons in the car. Continuing on, a few miles south of Springfield, defendant pulled out a pistol and pointed it at one of the hitchhikers, demanding his money. One of the other occupants of the car produced a knife and held it against the other hitchhiker. One dollar, a watch and watchband were taken from the hitchhikers. They were then let out of the car. Their wallets were returned to them, but their suitcases were not. Just before the automobile pulled away, defendant fired two shots in the direction of the hitchhikers.
The victims ran to a nearby service station and notified the Illinois State police of the robbery. Defendant was apprehended by Springfield city police officers a short time later.
A jury found defendant guilty of both robbery and armed robbery. A sentence of 10 to 30 years in prison was imposed on the armed robbery verdict, no sentence being imposed on the judgment of guilty on the robbery charge. The trial court found a sentence greater than the minimum was required. The probation report showed that the defendant admitted he was "high" on the night of the offense from smoking marijuana. It was also noted defendant had been carrying a gun with which he committed the offense. The court concluded the gun was carried for some illegal purpose. The court also mentioned that defendant had been a.w.o.l. from military service. Finally, the court pointed out that defendant had fired two shots in the direction of the victims after the armed robbery was completed and they were out of the car.
1 The State had confessed error in the entry of judgment on the robbery verdict when both verdicts arose out of the same course of conduct. Under People v. Lilly, 56 Ill.2d 493, 309 N.E.2d 1, the robbery conviction must be vacated.
The presentencing report filed by the chief probation officer recommended *684 the court consider the minimum sentence for defendant. This report showed defendant's adult arrest record contained no felony convictions other than the offenses involved here. Defendant had no history of drug abuse other than occasional marijuana use. Defendant had been a.w.o. 1. from the U.S. Marine Corps for a period of time and received a discharge under conditions other than honorable on March 1, 1973. Defendant had denied firing the two shots at the robbery victim, claiming a cohort had done it in an attempt to scare them.
The Illinois Constitution, 1970, article 1, section 11, sets forth guides for courts in imposing penalties:
"All penalties shall be determined both according to the seriousness of the offense and with the objective of restoring the offender to useful citizenship. * * *"
Armed robbery is a Class 1 felony for which an offender may not be sentenced to death. (Ill. Rev. Stat. 1973, ch. 38, par. 18-2(b).) Defendant could have been sentenced to any maximum term in excess of 4 years. (Ill. Rev. Stat. 1973, ch. 38, par. 1005-8-1(b)(2).) The minimum term shall be 4 years for a Class 1 felony unless the court, having regard for the nature and circumstances of the offense and history and character of the defendant, sets a higher minimum term. Ill. Rev. Stat. 1973, ch. 38, par. 1005-8-1(c) (2).
2 This court has the power under Supreme Court Rule 615(b) (Ill. Rev. Stat. 1973, ch. 110A, par. 615(b)(4)), to reduce the defendant's sentence if it is manifestly excessive. However, we are aware that this authority to reduce sentences should be used with caution and circumspection, as sentence disposition is peculiarly within the discretion of the trial court. (People v. Taylor, 33 Ill.2d 417, 211 N.E.2d 673; People v. Caldwell, 39 Ill.2d 346, 236 N.E.2d 706.) However, when a particular case requires it, we will exercise our authority under Supreme Court Rule 615(b)(4). People v. House, 26 Ill. App.3d 330, 325 N.E.2d 69.
The writer is persuaded that this is an appropriate case for a reduction of sentence. The minimum sentence of 2 1/2 times that mandated by the statute was imposed by the trial court upon this defendant for what is essentially his first felony conviction. In my view, that is excessive and disparate to the sentence imposed upon an associate in the offense, William Wayne Gray, whose sentence of 1 to 3 years upon a plea of guilty to robbery was affirmed by a Rule 23 Order (4th Dist. No. 12902, aff'd, 8/21/75). The other two members of the panel are not persuaded that this is a case for reduction of sentence and, accordingly, this court will not exercise the authority to reduce the sentence. The judgment of conviction for armed robbery is affirmed; the conviction for robbery is vacated; and this cause is remanded to the circuit court of Sangamon *685 County with directions to issue an amended mittimus in accordance with the views herein expressed.
Conviction for robbery vacated; conviction for armed robbery affirmed; cause remanded with directions.
SIMKINS, P.J., and TRAPP, J., concur.
| 2023-09-11T01:26:28.774034 | https://example.com/article/3621 |
Scaling in force spectroscopy of macromolecules.
We use molecular dynamics to determine the force needed to rupture a chain molecule being stretched at constant loading rate and temperature. When all energy bonds of the molecule are identical, we find that the force F depends on the pulling rate r and temperature T according to F approximately const- T(1/3)|ln (r/T)|(1/3). When a single weak bond is introduced, this result is modified to F approximately const - T(2/3|ln (r/T)(2/3)|. This scaling, which is model independent, can be used with experiment to quantitatively extract relevant microscopic parameters. | 2023-10-30T01:26:28.774034 | https://example.com/article/1393 |
Q:
hardcode pointer value
char buf[50];
char *ptr = buf;
How can I hardcode a space (' ') into a specific pointer locations if I want to hardcode (' ') in 4th, 8th and 16th pointer location?
A:
*(ptr+3) = ' ';
*(ptr+7) = ' ';
*(ptr+15) = ' ';
A:
If by hardcoding you mean that you want the value before starting any execution (as oposed to Till's answer), you could do something like:
char buf[50] = "... ... ....... ";
and then the rest of your code. (Note that positions that are not spaces have a value that is irrelevant.
| 2024-03-03T01:26:28.774034 | https://example.com/article/7620 |
Phenotypic and molecular characterization of macrolide and streptogramin resistance in Streptococcus mitis from neutropenic patients.
To determine the prevalence of macrolide and streptogramin resistance in Streptococcus mitis isolates from neutropenic patients and to identify mechanisms of macrolide and streptogramin resistance in resistant isolates. MICs of erythromycin, spiramycin, lincomycin and pristinamycin were determined for S. mitis isolates. Macrolide-resistance genes were characterized by PCR and ribosomal mutations by sequencing. A total of 169 S. mitis isolates were recovered from 66 patients at the Tunisian Bone Marrow Transplant Centre. Of these, 120 (70%) were non-susceptible to erythromycin and one was resistant to pristinamycin; 48.5% of isolates had an MLSB phenotype with cross-resistance between erythromycin, spiramycin and lincomycin, 4% had a dissociated MLSB phenotype with resistance to erythromycin and spiramycin but apparent susceptibility to lincomycin and 47.5% displayed the M phenotype. Resistance determinants were characterized in 33 isolates. Ten of 14 isolates with the cross MLSB resistance contained an ermB-like gene and four a combination of ermB- and mefA-like genes. Four of the five isolates with a dissociated MLSB phenotype contained ermB-like and one a combination of ermB- and mefA-like genes. All the 14 isolates with an M phenotype contained mefA-like genes. The pristinamycin-resistant strain had G105 and A108 substitutions in the conserved C terminus of the L22 ribosomal protein. The prevalence of macrolide resistance is high in S. mitis from neutropenic patients and is due to the spread of ermB- or mefA-like genes alone or combined. Resistance to streptogramins is rare and in this case associated with ribosomal mutation. | 2024-04-15T01:26:28.774034 | https://example.com/article/3712 |
Q:
Why is XML::Simple Discouraged?
From the documentation of XML::Simple:
The use of this module in new code is discouraged. Other modules are available which provide more straightforward and consistent interfaces. In particular, XML::LibXML is highly recommended.
The major problems with this module are the large number of options and the arbitrary ways in which these options interact - often with unexpected results.
Can someone clarify for me what the key reasons for this are?
A:
The real problem is that what XML::Simple primarily tries to do is take XML, and represent it as a perl data structure.
As you'll no doubt be aware from perldata the two key data structures you have available is the hash and the array.
Arrays are ordered scalars.
hashes are unordered key-value pairs.
And XML doesn't do either really. It has elements which are:
non uniquely named (which means hashes don't "fit").
.... but are 'ordered' within the file.
may have attributes (Which you could insert into a hash)
may have content (But might not, but could be a unary tag)
may have children (Of any depth)
And these things don't map directly to the available perl data structures - at a simplistic level, a nested hash of hashes might fit - but it can't cope with elements with duplicated names. Nor can you differentiate easily between attributes and child nodes.
So XML::Simple tries to guess based on the XML content, and takes 'hints' from the various option settings, and then when you try and output the content, it (tries to) apply the same process in reverse.
As a result, for anything other than the most simple XML, it becomes unwieldy at best, or loses data at worst.
Consider:
<xml>
<parent>
<child att="some_att">content</child>
</parent>
<another_node>
<another_child some_att="a value" />
<another_child different_att="different_value">more content</another_child>
</another_node>
</xml>
This - when parsed through XML::Simple gives you:
$VAR1 = {
'parent' => {
'child' => {
'att' => 'some_att',
'content' => 'content'
}
},
'another_node' => {
'another_child' => [
{
'some_att' => 'a value'
},
{
'different_att' => 'different_value',
'content' => 'more content'
}
]
}
};
Note - now you have under parent - just anonymous hashes, but under another_node you have an array of anonymous hashes.
So in order to access the content of child:
my $child = $xml -> {parent} -> {child} -> {content};
Note how you've got a 'child' node, with a 'content' node beneath it, which isn't because it's ... content.
But to access the content beneath the first another_child element:
my $another_child = $xml -> {another_node} -> {another_child} -> [0] -> {content};
Note how - because of having multiple <another_node> elements, the XML has been parsed into an array, where it wasn't with a single one. (If you did have an element called content beneath it, then you end up with something else yet). You can change this by using ForceArray but then you end up with a hash of arrays of hashes of arrays of hashes of arrays - although it is at least consistent in it's handling of child elements. Edit: Note, following discussion - this is a bad default, rather than a flaw with XML::Simple.
You should set:
ForceArray => 1, KeyAttr => [], ForceContent => 1
If you apply this to the XML as above, you get instead:
$VAR1 = {
'another_node' => [
{
'another_child' => [
{
'some_att' => 'a value'
},
{
'different_att' => 'different_value',
'content' => 'more content'
}
]
}
],
'parent' => [
{
'child' => [
{
'att' => 'some_att',
'content' => 'content'
}
]
}
]
};
This will give you consistency, because you will no longer have single node elements handle differently to multi-node.
But you still:
Have a 5 reference deep tree to get at a value.
E.g.:
print $xml -> {parent} -> [0] -> {child} -> [0] -> {content};
You still have content and child hash elements treated as if they were attributes, and because hashes are unordered, you simply cannot reconstruct the input. So basically, you have to parse it, then run it through Dumper to figure out where you need to look.
But with an xpath query, you get at that node with:
findnodes("/xml/parent/child");
What you don't get in XML::Simple that you do in XML::Twig (and I presume XML::LibXML but I know it less well):
xpath support. xpath is an XML way of expressing a path to a node. So you can 'find' a node in the above with get_xpath('//child'). You can even use attributes in the xpath - like get_xpath('//another_child[@different_att]') which will select exactly which one you wanted. (You can iterate on matches too).
cut and paste to move elements around
parsefile_inplace to allow you to modify XML with an in place edit.
pretty_print options, to format XML.
twig_handlers and purge - which allows you to process really big XML without having to load it all in memory.
simplify if you really must make it backwards compatible with XML::Simple.
the code is generally way simpler than trying to follow daisy chains of references to hashes and arrays, that can never be done consistently because of the fundamental differences in structure.
It's also widely available - easy to download from CPAN, and distributed as an installable package on many operating systems. (Sadly it's not a default install. Yet)
See: XML::Twig quick reference
For the sake of comparison:
my $xml = XMLin( \*DATA, ForceArray => 1, KeyAttr => [], ForceContent => 1 );
print Dumper $xml;
print $xml ->{parent}->[0]->{child}->[0]->{content};
Vs.
my $twig = XML::Twig->parse( \*DATA );
print $twig ->get_xpath( '/xml/parent/child', 0 )->text;
print $twig ->root->first_child('parent')->first_child_text('child');
A:
XML::Simple is the most complex XML parser available
The main problem with XML::Simple is that the resulting structure is extremely hard to navigate correctly. $ele->{ele_name} can return any of the following (even for elements that follow the same spec):
[ { att => 'val', ..., content => [ 'content', 'content' ] }, ... ]
[ { att => 'val', ..., content => 'content' }, ... ]
[ { att => 'val', ..., }, ... ]
[ 'content', ... ]
{ 'id' => { att => 'val', ..., content => [ 'content', 'content' ] }, ... }
{ 'id' => { att => 'val', ..., content => 'content' }, ... }
{ 'id' => { att => 'val', ... }, ... }
{ 'id' => { content => [ 'content', 'content' ] }, ... }
{ 'id' => { content => 'content' }, ... }
{ att => 'val', ..., content => [ 'content', 'content' ] }
{ att => 'val', ..., content => 'content' }
{ att => 'val', ..., }
'content'
This means that you have to perform all kinds of checks to see what you actually got. But the sheer complexity of this encourages developers to make very bad assumptions instead. This leads to all kinds of problems slipping into production, causing live code to fail when corner cases are encountered.
The options for making a more regular tree fall short
You can use the following options to create a more regular tree:
ForceArray => 1, KeyAttr => [], ForceContent => 1
But even with these options, many checks are still needed to extract information from a tree. For example, getting the /root/eles/ele nodes from a document is a common operation that should be trivial to perform, but the following is required when using XML::Simple:
# Requires: ForceArray => 1, KeyAttr => [], ForceContent => 1, KeepRoot => 0
# Assumes the format doesn't allow for more than one /root/eles.
# The format wouldn't be supported if it allowed /root to have an attr named eles.
# The format wouldn't be supported if it allowed /root/eles to have an attr named ele.
my @eles;
if ($doc->{eles} && $doc->{eles}[0]{ele}) {
@eles = @{ $doc->{eles}[0]{ele} };
}
In another parser, one would use the following:
my @eles = $doc->findnodes('/root/eles/ele');
XML::Simple imposes numerous limitations, and it lacks common features
It's completely useless for producing XML. Even with ForceArray => 1, ForceContent => 1, KeyAttr => [], KeepRoot => 1, there are far too many details that can't be controlled.
It doesn't preserve the relative order of children with different names.
It has limited (with XML::SAX backend) or no (with XML::Parser backend) support for namespaces and namespace prefixes.
Some backends (e.g. XML::Parser) are unable to handle encodings not based on ASCII (e.g. UTF-16le).
An element can't have a child element and an attribute with the same name.
It can't create XML documents with comments.
Ignoring the major issues previously mentioned, XML::Simple could still be usable with these limitations. But why go to the trouble of checking if XML::Simple can handle your document format and risk having to switch to another parser later? You could simply use a better parser for all your documents from the start.
Not only do some other parsers not subject you to these limitations, they provide loads of other useful features in addition. The following are a few features they might have that XML::Simple doesn't:
Speed. XML::Simple is extremely slow, especially if you use a backend other than XML::Parser. I'm talking orders of magnitude slower than other parsers.
XPath selectors or similar.
Support for extremely large documents.
Support for pretty printing.
Is XML::Simple ever useful?
The only format for which XML::Simple is simplest is one where no element is optional. I've had experience with countless XML formats, and I've never encountered such a format.
This fragility and complexity alone are reasons enough to warrant staying away from XML::Simple, but there are others.
Alternatives
I use XML::LibXML. It's an extremely fast, full-featured parser. If I ever needed to handle documents that didn't fit into memory, I'd use XML::LibXML::Reader (and its copyCurrentNode(1)) or XML::Twig (using twig_roots).
A:
I disagree with the docs
I'll dissent and say that XML::Simple is just that.. simple. And, it's always been easy and enjoyable for me to use. Test it with the input you're receiving. So long as the input does not change, you're good. The same people that complain about using XML::Simple complain about using JSON::Syck to serialize Moose. The docs are wrong because they take into account correctness over efficiency. If you only care about the following, you're good:
not throwing away data
building to a format supplied and not an abstract schema
If you're making an abstract parser that isn't defined by application but by spec, I'd use something else. I worked at a company one time and we had to accept 300 different schemas of XML none of which had a spec. XML::Simple did the job easily. The other options would have required us to actually hire someone to get the job done. Everyone thinks XML is something that is sent in a rigid all encompassing spec'ed format such that if you write one parser you're good. If that's the case don't use XML::Simple. XML, before JSON, was just a "dump this and walk" format from one language to another. People actually used things like XML::Dumper. No one actually knew what was outputted. Dealing with that scenario XML::Simple is greattt! Sane people still dump to JSON without spec to accomplish the same thing. It's just how the world works.
Want to read the data in, and not worry about the format? Want to traverse Perl structures and not XML possibilities? Go XML::Simple.
By extension...
Likewise, for most applications JSON::Syck is sufficient to dump this and walk. Though if you're sending to lots of people, I'd highly suggest not being a douche nozzle and making a spec which you export to. But, you know what.. Sometime you're going to get a call from someone you don't want to talk to who wants his data that you don't normally export. And, you're going to pipe it through JSON::Syck's voodoo and let them worry about it. If they want XML? Charge them $500 more and fire up ye' ole XML::Dumper.
Take away
It may be less than perfect, but XML::Simple is damn efficient. Every hour saved in this arena you can potentially spend in a more useful arena. That's a real world consideration.
The other answers
Look XPath has some upsides. Every answer here boils down to preferring XPath over Perl. That's fine. If you would rather use an a standardized XML domain specific language to access your XML, have at it!
Perl doesn't provide for an easy mechanism to access deeply nested optional structures.
var $xml = [ { foo => 1 } ]; ## Always w/ ForceArray.
var $xml = { foo => 1 };
Getting the value of foo here in these two contexts can be tricky. XML::Simple knows this and that's why you can force the former.. However, that even with ForceArray, if the element isn't there you'll throw an error..
var $xml = { bar => [ { foo => 1 } ] };
now, if bar is optional, You're left accessing it $xml->{bar}[0]{foo} and @{$xml->{bar}}[0] will throw an error. Anyway, that's just perl. This has 0 to do with XML::Simple imho. And, I admitted that XML::Simple is not good for building to spec. Show me data, and I can access it with XML::Simple.
| 2024-03-18T01:26:28.774034 | https://example.com/article/3938 |
Avidin-biotin technology in targeted therapy.
The goal of drug targeting is to increase the concentration of the drug in the vicinity of the cells responsible for disease without affecting healthy cells. Many approaches in cancer treatment are limited because of their broad range of unwanted side effects on healthy cells. Targeting can reduce side effects and increase efficacy of drugs in the patient. Avidin, originally isolated from chicken eggs, and its bacterial analogue, streptavidin, from Streptomyces avidinii, have extremely high affinity for biotin. This unique feature is the basis of avidin-biotin technology. This article reviews the current status of avidin-biotin systems and their use for pretargeted drug delivery and vector targeting. The reader will gain an understanding of the following approaches using the avidin-biotin system: i) targeting antibodies and therapeutic molecules are administered separately leading to a reduction of drug dose in normal tissues compared with conventional (radio)immunotherapies; ii) introducing avidin gene into specific tissues by local gene transfer, which subsequently can sequester and concentrate considerable amounts of therapeutic ligands; and iii) enabling transductional targeting of gene therapy vectors. Avidin and biotin technology has proved to be an extremely versatile tool with broad applications, such as pretargeting, delivering avidin gene into cells enabling targeting of biotinylated compounds and targeting of viral vectors. | 2024-05-04T01:26:28.774034 | https://example.com/article/6353 |
Background {#Sec1}
==========
In Liberia, malaria is one of the most prevalent causes of death \[[@CR1]\]. With a resource-constrained health system as a result of a decade-long civil war \[[@CR2]\], Liberia needed massive foreign aid to control the recent 2014--2016 Ebola epidemics \[[@CR3]\], which left over 4000 deaths \[[@CR4]\] and depleted its already scarce healthcare workforce \[[@CR5]\]. The crisis resulted in a disruption in the provision of malaria control interventions that led to an increase of malaria-attributable mortality \[[@CR6], [@CR7]\]. Pregnant women, a population particularly susceptible to malaria infection \[[@CR1], [@CR8], [@CR9]\], suffered the closure of health facilities and the fear of qualified professionals to assist their deliveries \[[@CR10]\]. In spite of efforts to scale up malaria prevention after the epidemic, uptake of intermittent preventive treatment in pregnancy (IPTp) and insecticide-treated nets (ITN) by pregnant women has not increased substantially. According to the 2011 and 2016 Malaria Indicator Surveys, the percentage of women who had taken two or more doses of sulfadoxine--pyrimethamine-based IPTp increased from 50.0 to 54.5% and the percentage of women who slept under an ITN the night before increased from 39 to 40% \[[@CR11], [@CR12]\].
Advances to protect pregnant women against malaria depend on the development of efficient vector control as well as preventive and therapeutic strategies \[[@CR9]\]. It has been shown that IPTp has a great potential to reduce the incidence and consequences of malaria in pregnant women \[[@CR13]--[@CR15]\] and that it can prevent low birth weight \[[@CR16]\] or premature death among their offspring \[[@CR16]--[@CR18]\]. However, as evidenced by national survey data, full coverage of IPTp is difficult to achieve. Therefore, there appears to be a need to design innovative strategies to improve malaria prevention during pregnancy \[[@CR1], [@CR8], [@CR9]\]. In order to convince National Malaria Control Programme (NMCP) planners of the utility of novel interventions for pregnant women, it is important that they are trialled in-country in the frame of rigorous research. However, in addition to being especially vulnerable to malaria infection, pregnant women are also a vulnerable study population that deserves special protection measures \[[@CR19]--[@CR22]\].
During the Ebola epidemic, a number of vaccine and drug clinical trials were initiated \[[@CR23]--[@CR25]\]. There was little time for thorough planning of research due to the urgency to find biomedical solutions to halt the spread of the virus \[[@CR25]\]. The trials signified the arrival of funds, equipment, laboratories, researchers and knowledge \[[@CR26]\]. Whilst some trials were prematurely terminated due to the impossibility to continue recruitment of Ebola-infected subjects \[[@CR24], [@CR27]\], other trials gave origin to research platforms that persist today. One such platform is the 'Liberia--US Clinical Trials Partnership Program, Partnership for Research on Ebola Vaccines in Liberia' (PREVAIL) \[[@CR23], [@CR28]\]. The maintenance of research activities has given the opportunity to look back and reflect on the management of patients during the Ebola outbreak, the conduct of clinical trials, the provision of routine healthcare services to the general population, and how traditional cultural values might have affected how the Liberians perceive researchers and research activities involving community participation and data and specimen collection.
The conditions under which vulnerable populations are recruited as study participants have long been of concern to bioethicists and trialists \[[@CR27], [@CR29], [@CR30]\]. A number of qualitative studies have been conducted in a variety of settings, including Burkina Faso \[[@CR31]\], Gabon \[[@CR32]\], Ghana \[[@CR33]--[@CR35]\], Kenya \[[@CR36], [@CR37]\], or The Gambia \[[@CR38], [@CR39]\], to understand the impact of research on the populations' value placed in research \[[@CR38]\]; researchers' expressed challenges to apply ethical principles \[[@CR32]\]; efficacy of informed consent process \[[@CR31], [@CR36]\]; the influence of the community leaders and household heads in individuals' decision to consent \[[@CR33], [@CR39]\]; or in parental and male partners' comprehension of the consent process \[[@CR35], [@CR37]\]. Another issue of growing concern is how the exclusion of pregnant women from vaccine and drug trials may foster---rather than minimize---their susceptibility to further ill health \[[@CR27]\].
There is need for such type of qualitative studies for Liberia that analyse---beyond Ebola---the conditions under which future clinical and socio-behavioural research on other prevalent infectious diseases (e.g. malaria) will be conducted. Together with baseline epidemiological data, socio-anthropological data on how Liberian communities experience and understand research is indispensable to inform future research with the aim of enhancing malaria prevention and control, particularly among pregnant women.
Methods {#Sec2}
=======
Aim, site and period {#Sec3}
--------------------
A qualitative inquiry with the aim to understand the barriers and opportunities for pregnant women to participate in malaria research in Liberia was conducted. This article reports on community members' perceptions and attitudes towards research as well as on the contextual aspects that may deter or motivate pregnant women to participate in malaria research.
The study was conducted between November 2016 and May 2017 in parallel with a cross-sectional study on the prevalence of malaria among pregnant women attending antenatal care at the Saint Joseph's Catholic Hospital (SJCH). The SJCH is a not-for-profit maternal referral hospital in Congo Town neighbourhood, in Monrovia. Monrovia, Liberia's capital, is the largest city in Montserrado County, one of the 15 administrative divisions of the country.
In mid-2016, the SJCH, with support from the Barcelona Institute for Global Health (ISGlobal), trained in medical research ethics a group of traditional community representatives and constituted a Community Advisory Board (C.A.B). The SJCH C.A.B members provided advice for the design of this qualitative study.
Sampling {#Sec4}
--------
Three groups of key-informants (KI) were invited to participate: (KI1) SJCH medical, laboratory, and management staff: (KI2) Traditional community representatives participants to the C.A.B. outreach activities: (KI3) Pregnant women that previously participated in the malaria prevalence study. All those younger than 18 years and unwilling to give consent were excluded.
Convenience sampling was used to approach, face by face, informants for KI1 and KI2 groups. Purposive sampling served to approach, by phone, informants for group KI3. Study recruitment forms from the malaria prevalence study were used to generate a randomized list of pregnant women to approach in this study.
The purpose of the study was explained and, if interested, a date was scheduled for the approached individual to meet the social scientist (GMP) at the SJCH facilities. At the scheduled date, informed consent was obtained. Two different information sheet and consent forms were used: one for the in-depth interviews (IDIs) and one for the focus group discussions (FGDs). Participants to the FGDs were reminded of the importance of keeping information shared by the other participants confidential. During the consent process, all informants were made aware of their rights to withdraw from the study at any time with no penalty, and their right to not answer any question they did not want.
All participants received a grocery voucher of 10.00 USD for their participation. As data collection and analysis was done iteratively, when saturation \[[@CR40]\]---the point at which all concepts and categories were fully understood---was reached, recruitment was discontinued.
Data collection and management {#Sec5}
------------------------------
A thematic guide was used to gain insights about the participants' views on malaria disease and on health research. Data collection was led in English by a male social scientist (GMP) with experience in qualitative research in sub-Saharan Africa, and aided by a local trained female co-interviewer who used 'colloquia' (Liberian English). No one else was present during data collection, which was done in a private office at the SJCH. Most participants, especially from KI2 and KI3, preferred to use 'colloquia' when answering the questions posed. Neither the social scientist nor the co-interviewer had any clinical or contractual relationship with any of the interviewees.
IDIs and FGDs were taped and were an average of 53 and 72 min in length, respectively. All recordings were transcribed verbatim in a password-protected computer. Transcriptions were cross-checked against the recordings. If there were inconsistencies, the transcripts were amended. All personal identifiers were removed from the transcriptions. Consent forms, recordings and transcriptions received a Unique Identification Number to enable linkage of documents. The transcripts were uploaded into Dedoose software (^®^SocioCultural Research Consultants, Manhattan Beach, CA). After data coding and analysis, all recordings were deleted to further protect participants' confidentiality.
Analysis {#Sec6}
--------
All transcripts were coded contemporaneously with data collection to ensure that all core concepts were addressed with the participants. No themes and codes were pre-defined. At first, data were line-by-line hand-coded using gerunds and making use of participants' own words \[[@CR40]\]. Once a final coding framework was defined during the first interviews, this framework was used to code the rest of the transcripts.
A feminist interpretation of grounded theory was used \[[@CR41]--[@CR43]\]. This interpretation involves that women participants are considered 'co-generators' of theory in cooperation with the social scientist. The social scientist is expected to practice reflexivity throughout her/his interactions with the participants, and to be sensitive towards issues of oppression and marginality. This approach prioritizes that research findings are useful for social change and to improve women's health.
Different measures were used to guarantee the trustworthiness of this study. Participants' answers from the IDIs were triangulated with their answers from the FGDs. During data collection, the social scientist kept a memo journal to reflect on the impact of his interaction with the women participants. Thoughtful care was put to map and analyse deviant cases. Throughout analysis and reporting, women's own words were used to define concepts and categories. In the Results section, participants' perspectives are expressed in their own words using *'italics'*. As majority of participants' narratives were in 'colloquia', excerpts have been edited for grammar correction. Excerpts have been carefully chosen to ensure they represent the findings and that the deviant viewpoints are also represented. Additionally, peer-checks were done on the final analysis. This article has been prepared as per qualitative research reporting standards set in the COREQ checklist \[[@CR44]\].
Ethics approval {#Sec7}
---------------
The study was approved by the University of Liberia-Pacific Institute of Research & Evaluation Institution Review Board (Monrovia) and by the Hospital Clinic Research Ethics Committee (Barcelona).
Results {#Sec8}
=======
Seventeen pregnant women (hereafter referred to as *women*), 11 traditional community representatives (the *leaders*), and 10 SJCH workers (the *staff*) participated (Table [1](#Tab1){ref-type="table"}). There were no refusals. 26 IDIs and three FGDs were conducted. Five *staff*, five *leaders* and five *women* separately partook in the three FGDs. Thirty of the 38 participants were female. The median age was 35. Twenty-nine were born in Montserrado County. Sixteen and 11 participants had graduated from secondary and university education respectively. Unless stated otherwise, viewpoints reported in this section were common across KI groups.Table 1Basic socio-demographics of key informants (KI)Recording\#SexDepartmentAge groupCounty of birthEducationIDIFGDKI1: SJCH Medical, Administrative and Laboratory *staff*IDI5FGD1FMedical31--40MontserradoUniversityn.iMAdministrative51--60MontserradoUniversityn.iFMedical31--40MontserradoUniversityn.iFMedical21--30MontserradoUniversityn.iFMedical31--40MontserradoUniversityIDI4--MLaboratory31--40MontserradoUniversityIDI6--MMedical41--50Grand BassaUniversityIDI7--FMedical31--40MontserradoUniversityIDI15--FMedical31--40NimbaCollegeIDI16--FMedical51--60MontserradoCollegeRecording\#SexTraditional roleAge groupCounty of birthEducationIDIFGDKI2: Traditional *leaders* participants to the SJCH Community Advisory Board outreach activitiesIDI1FGD2MYouth leader31--40MontserradoSecondaryIDI10FChairlady41--50MontserradoNonen.iMCouncil of Elders41--50MontserradoUniversityn.iMCouncil of Elders51--60MontserradoSecondaryn.iFChairlady31--40MontserradoUniversityIDI2n.iFChairlady51--60MontserradoSecondaryIDI3n.iMChief41--50MontserradoUniversityIDI8n.iFChairlady41--50MontserradoSecondaryIDI9n.iFTrad. Midwife61--65MontserradoVocationalIDI11n.iMHerbalist51--60MontserradoSecondaryIDI12n.iMCouncil of Elders51--60MontserradoCollegeRecording\#SexCurrent occupationAge groupCounty of birthEducationIDIFGDKI3: pregnant *women* participants in malaria prevalence studyn.iFGD3FStudent18--20MontserradoSecondaryn.iFStudent31--40MontserradoNonen.iFStudent21--30MontserradoSecondaryn.iFBusiness31--40MargibiVocationaln.iFStudent31--40SinouCollegeIDI13n.iFStudent21--30MontserradoSecondaryIDI14n.iFStudent21--30RivercessSecondaryIDI17n.iFBusiness21--30MontserradoNoneIDI18n.iFStudent21--30MontserradoSecondaryIDI19n.iFBusiness21--30BongSecondaryIDI20n.iFBusiness21--30MontserradoSecondaryIDI21n.iFStudent21--30MontserradoSecondaryIDI22n.iFStudent21--30NimbaSecondaryIDI23n.iFPhysician Assist.21--30MontserradoCollegeIDI24n.iFStudent21--30Grand CapeSecondaryIDI25n.iFBusiness21--30Grand BassaPrimaryIDI26n.iFStudent21--30MontserradoSecondary*n.i* not interviewed: participants who only partook either in an IDI or in a FGD
Understanding the utility of research {#Sec9}
-------------------------------------
Educating the general population on the role of health research is a much needed investment. As explained by the *staff*, even healthcare professionals were not being trained in the fundaments of research at the university. The situation worsened among the low-income population. As one *leader* explained, education on research needs to target especially the people '*in the rural'* and those '*sleeping in the muddy areas'* in Monrovia.
When asked to express, in their own words, what research entitled, most described that its aim is finding *'solutions'* to people's problems. There was consensus that the main contribution of malaria research would be the development of more acceptable preventive tools. The *leaders* also expressed that research could contribute with data useful to motivate the women not to '*overlook'* malaria.
To exemplify the potential utility of malaria research, one *leader* recalled what the contribution of research during the Ebola epidemic was:"*In research you are going to find what medicine you can do to help people fight the disease that is coming. Take for example the Ebola. When it came to Liberia; nobody had any idea! Many people died. But later on they got an idea when they did that research.* (IDI 2)"
Many participants, including *staff*, mistook research for public health and healthcare provision. As argued by *staff* and *leaders*, lack of clear understanding on how research differs from other interventions could make pregnant women expect preventive, diagnostic or therapeutic benefits. If these expectations were not met, they would be disappointed. Thus, to build trust in the population, it would be crucial to promote education on the long-term societal benefits of health research in general and of malaria research in particular.
Capitalizing on past experiences to inform malaria research {#Sec10}
-----------------------------------------------------------
Participants' knowledge on past research experiences was explored. Some participants mentioned public health interventions instead: humanitarian aid to war refugees, polio and measles vaccination, male circumcision campaigns, and community sanitation. A few participants reported that they were themselves engaged as surveyors in malaria awareness carried by *'Youth Save'*, as community mobilizers for *'Red Cross*' during the Ebola crisis, or as health promoters for *'Médecins Sans Frontières'* during a cholera outbreak.
Some of the methods witnessed in public health interventions were mentioned as ideas to plan future malaria research. For instance, as one *woman* described, field research staff could be selected *'in a raffle'*, as allegedly done by organizations such as *'Mercy Corps'.* One *leader* suggested that some of the communication strategies used during the war---such as calls for blood donation---could be used to motivate women to accept giving blood specimens during malaria research. The use of *'drama'*, which was used during the post-war time, was also proposed to mobilize women:"*The UNMIL Mission in Liberia for peace*-*keeping. They had a peace message to give out. They used to have a comedian. He'd go, he'd perform, and you'd see people come. After performing, they \[the UNMIL staff\] would come and give the message.* (IDI 4)"
The only health research mentioned was the *'PREVAIL Ebola vaccine'* and the *'Z*-*Mapp drug'* trials. Insufficient information to the population on these trials gave rise to fears about the safety of the experimental interventions. These fears were described as potential deterrents for pregnant women to engage in malaria research although only a few participants admitted sharing these fears. Three *staff* disclosed that they had worked in an Ebola Treatment Unit (ETU) where participants to the abovementioned trials were recruited. One of them said that she decided not to participate in PREVAIL after she witnessed how a colleague '*took the Ebola vaccine'* and '*got signs and symptoms of Ebola'*. One *staff* and one *woman* explained how they had heard that the *'PREVAIL vaccine'* and the '*Z*-*Mapp drug'* were '*killing people'*."*Doctor \[Name of local physician\] was one of those who took the vaccine and said: 'As an example, I'm taking the vaccine, and it is not harmful'. But when \[later\] he died, many people started saying: 'The doctor died. He took the vaccine, and that killed him'. It was not official. But people were discussing it in street corners.* (IDI 4)"
The belief that people were given Ebola intentionally at the ETUs through *'injections'* may lead some women to refuse the administration of experimental vaccines in the future. As one *leader* explained, during a recent polio vaccination, some mothers were reluctant to vaccinate their children because they suspected that unidentified foreigners were *'bringing the Ebola vaccine to kill people!'* Some women may also refuse to give blood specimens because another common belief was that the Ebola virus was *'man*-*made*'. Hence, as one *staff* expressed, some women may refuse to participate in malaria research in order to prevent their blood being used to '*fabricate other viruses again'*:"*I saw it on the internet. That Black American defending that Ebola was not a virus, that it was a chemical that they produced, and that the scientists were checking whether it could kill. And then the President Ellen Johnson Sirleaf and her colleague \[Queen Sheba\] agreed that they should come to try it in Liberia.* (IDI 22)"
Interacting with healthcare workers: barriers to overcome {#Sec11}
---------------------------------------------------------
Throughout all IDIs and FGDs, the participants reflected on how *'rampant corruption'* and the interactions between healthcare workers and their patients could influence their own as well as other people's attitudes towards malaria research conducted in healthcare institutions. Corruption was described as a problem that impregnated all aspects of public life in Liberia. '*Bribes*' were described as commonplace in government-run facilities. One *woman* thought that this was the consequence of the government *'taking long to pay staff salaries'.* Healthcare workers were also suspected to supply *'drugstores'* nearby with anti-malarial drugs taken from the clinics. All *women* expressed that many pregnant women *'feel discouraged'* when healthcare workers refuse to give them the prescribed drugs for malaria: *'Little money! Any buddy you meet. They say: 'Pay small thing'?'* In general, the participants were not optimistic about what women could do to ensure their right to healthcare access:"*The government is not able to fight the corruption because the corruption starts from up there before it comes down... So, how are we the citizens going to fight the corruption when the corruption is rampant within the government?* (IDI 22)"
In addition to corruption, many Liberians may feel that they must accept anything prescribed to them by the health personnel. This widespread attitude of healthcare workers was identified as a potential deterrent for pregnant women to trust experimental treatments in future trials. As one *staff* explained, '*patients' right'* to negotiate their pathway care was a foreign concept to the population:"*When I was not a medical practitioner, I used to think that if I had to go to the doctor to seek for medical care, and then the doctor suggests anything to me, if I refuse, he or she will not pay attention to me.* (IDI 4)"
The fear to discover that the blood of participants might be *'sold'* by research staff was sustained by awareness that doctors and nurses consented for blood to be traded in the clinics. Many participants described how some individuals made a living by selling their blood directly to the patients at the hospitals. Two *leaders* narrated their own experiences buying blood at two different hospitals in Monrovia. One *woman*, who disclosed in one FGD that she had to buy blood for each one of the three C-sections that she had, defended this practice because the hospitals needed to recover the investment they made to keep the blood refrigerated.
*'Nothing for nothing'* was a motto frequently mentioned. In the frame of research, this notion would be *'running in people's minds'* because, as one *woman* explained, many would be convinced that researchers would sell their blood and personal data. The majority of participants suggested that pregnant women could be compensated financially for their participation in research. However, offering money may have downsides. *'Poverty'* could unduly influence women to accepting to become trial subjects. Two *staff* claimed that they knew research staff from *'PREVAIL*' and previous HIV surveys who complained that people tried to enrol several times in order to receive the retribution. As *staff* and *leaders* expressed, autonomy of women will be compromised:"*Money! You enticed me to do it, but it might not be in my mind, it might not be my will to do that.* (IDI 4)"
In addition to poverty, many pregnant women faced difficulties to access healthcare. Liberia has a mixed public--private health system, characterized by a very sparse network of health facilities. The population used two currencies: United States Dollars and Liberian Dollars. Fluctuations in the value of the Liberian Dollar affected access to clinic-based care. Hence, many participants claimed that, to ensure research findings could translate in improved prevention and therapies for pregnant women, it was key to ensure free access to healthcare in government facilities so that people could *'save their money'* rather than spending it in *'little somethings'* and *'drugstores'*.
As a result of their experiences at the clinics, many pregnant women distrust healthcare workers, dislike the healthcare system, resort to *'country medicine'* against their will, and self-initiate treatment with antipyretics and anti-malarial drugs that are easily available at *'chemist shops'* and '*black dealers'* (street vendors). As expressed by the participants, research could be useful to encourage women to seek biomedical healthcare and to demand their rights as patients. Malaria research could be helpful not only to develop new prevention and therapeutic means but also to identify all healthcare access problems that pregnant women face in Liberia. However, as discussed by one *leader*, if the healthcare system did not discontinue its pay-per-service system, the community would miss the opportunity to benefit from improved malaria control interventions.
Mobilizing the communities to engage in malaria research {#Sec12}
--------------------------------------------------------
Counting on general education alone would not be sufficient to promote the participation of pregnant women in research. *'Intensive positive research awareness campaigns*', as one *staff* put it, should be thoroughly planned in cooperation with the community leaders, and promptly put in place ahead of the conduct of malaria research. *'Announcements'* to the population may be done in market places, taxi ranks, churches, video clubs, and football fields. Organizing '*forums'* or *'palava hut discussions'* at schools, city halls, clinics, or at '*the junction of the road'* were proposed as preferred approaches to reach the communities. Going '*house by house'*, what two *leaders* termed '*Jehovah witness campaign'* was also valued as highly effective. Irrespective of the approach, any community-based mobilization must emphasize what the purpose of research is and what its potential individual and community '*disadvantages'* are.
Community mobilization for research should integrate health promotion activities for pregnant women explaining the aetiology of malaria as well as the most effective prevention, diagnostic and curative interventions. As rumours on experimental drugs and vaccines tested in previous trials might have originated fears and suspicions, two *staff* expressed that emphasis must be put in explaining to the communities that the only mean to develop better prevention and treatment tools is via the conduct of clinical trials:"*In the past there were no drugs for malaria. So people went and studied about the disease and how to prevent it. So, they did trials, they took samples and then they tested \[a drug in\] animals and then they tested it on humans. Over and over. And then they found out that it was good to treat malaria.* (IDI 7)"
In agreement with *women'* and *staff*'s suggestions, the *leaders* partaking in a FGD described the methodological approach of this study as an example of what researchers were expected to do: leave their hospitals or academic institutions; reach the communities and their traditional representatives; provide training on the fundaments of research; and collaboratively mobilize pregnant women."*You are the first person I see! I am fifty eight now. I live here. I was born here. I never saw people. So, if you tell me that we've got Liberian researchers... maybe they are doing research in their offices or in their bedrooms!* (IDI 11)"
Chiefs and chairladies were described as *'role models'* for the women that can authorize research, vaccination campaigns, and health promotion. As one female *leader* explained, if she were not engaged in the research, she would instruct the women *'not to talk to the researchers'*.
*'Sincere'* information on the research purpose and on the planned measures to safeguard pregnant women's confidentiality must be given to leaders, women and their partners, for them to make their own informed decision on whether to participate or not. Researchers will be expected to disclose the potential side effects of the experimental interventions and on the study tests. Importantly, researchers will need to reassure women that they '*will not be harmed'*. If convinced about the safety of the study, as one *leader* expressed, some community representatives would even participate or allow their relatives to participate:"*In Africa people build confidence in the leader. And the leader must lead. If the community people don't see me take the first step... So, to set an example, I would first allow my children to participate. And then the community would say: 'Oh! If you, of all people, can do it, then we will do it'.* (IDI 3)"
Many Liberians may mistrust researchers. Information on who the '*White researchers are'* will be expected. One *leader* proposed to describe researchers to women as people with '*humanitarian tendency'* who '*have love for life'.* As one chairlady expressed, she would tell the women that: *'The white man is not here to kill you!'*
Endorsement of the research by their traditional representatives will be essential. All *women* in this study explained that they would not consider that the researchers are '*serious'* unless they had heard '*announcements'* from the leaders. Once researchers are introduced formally, to build rapport among women, they must be '*polite', 'honest',* and *'humble'*. And they must use *colloquia*. A common complaint about researchers was that they talked '*fast, fast'* to induce people into accepting to engage in research. The most common perception was that researchers '*become rich'* by developing treatments that they would never bring back to Liberia. As one *staff* complained, the Liberians are '*the sacrificial lamb'* whilst the researchers reap the benefits."*They think you are picking the information to sell it down. Because some people think that many people who come on the field to educate people on HIV, malaria, at the end, they will say they will bring medicine, but they won't come back.* (IDI 25)"
Understanding tradition to better plan research {#Sec13}
-----------------------------------------------
The participants identified how, due to poorly designed communication on preventive measures during the Ebola outbreak, some Liberians were discouraged to adhere to the recommendations made by the health authorities. Many refused to believe that eating '*bush meat'* could lead to acquiring Ebola because the authorities' messages did not consider the cooking habits of the most impoverished. Some other people believed that Ebola was not caused by a virus but by their '*forefathers'* who '*were vexed'*. According to the participants, the lesson learnt from the Ebola outbreak is that cultural practices and beliefs need be mapped and understood when planning research on malaria or other diseases.
Engaging women in malaria research will be challenging when they hold on to traditional beliefs on the causes of infectious diseases. Many Liberian women, even in urban areas, might think disease---including malaria---may be caused by *'witchcraft'* and *'evil water spirits'*. Some people also believed in offering *'sacrifices'* to their *'forefathers'* to put an end to their ailments:"*People that died 50, 60, 40* *years ago: we still believe that they live among us. So, if the farming season is bad, we make sacrifices. We consult them, ok? Then, somebody would interpret that since we had done sacrifices, things will be all right.* (FGD 2)"
In this regard, research could be useful to help women disregard what they perceived as harmful beliefs that prevented them from seeking biomedical care for themselves and for their children. Women holding these beliefs may think that what affects them demands priority care from the *'herbalists*'.
The younger generations in Liberia were confronting the rationale behind many traditional beliefs and were embracing *'Western'* medicine. However, as one *leader* asked to other FGD members: *'How can we get rid of the people's belief? That is the question.'* Some perceived that health research could bring about change by helping people stop believing in '*witchcraft'* and '*forefathers'* as causes of disease and in *'country medicine'* and '*sacrifices'* as methods to address them. Women would not feel offended if researchers, accompanied by leaders, advised against '*country medicine'* and *'sacrifices'*. However, as most participants believed, advising women against the initiation ceremonies of the '*Sande secret society'* would be overly insensitive. Additionally, acknowledgement or suspicion that discussions on number of partners, abandonment of fathers of pregnancies, and illegal abortions might take place in the frame of research could make some women not accept to engage as study participants. One *staff* described these discussions as potentially '*embarrassing'*.
Mapping fears, inconveniences and expectations {#Sec14}
----------------------------------------------
Some pregnant women may not agree to give blood for research purposes because they may fear being diagnosed---against their will---with a stigmatizing disease such as HIV. In addition, some women might also fear that research staff takes the occasion to *'inject'* them *'a disease'* or a harmful substance to either make them '*infertile'* or to '*impregnate them*'.
As some people may fear that blood specimens could be marketed or used for other purposes, researchers' choice of methods for collecting and testing blood could also influence women's consent to give blood. People would be more comfortable if *'saliva'*-based rapid tests were used rather than '*venous blood'* tests. When no alternatives to blood-based tests existed, thorough face-to-face demonstration on the specimen collection procedures could be useful to allay women's fears:"*You tell them: 'We need to take blood from you to test you right now in your presence for malaria. This is the test. This is the syringe. This nurse will take your blood and test you straightaway.* (IDI 22)"
The risk of social harm and of breaches in confidentiality was described as a potential deterrent for women targeted as participants that researchers should consider seriously. Many women could feel *'shy'* to participate in interviews on malaria. Especially if women feared the interviews would be aired *'on the radio or on the television'*, and if they feared the researchers would *'judge their lifestyle'*:"*If you contracted the malaria because you were not using a treated mosquito net and the researcher asks you: 'What do you think your problem is? Why do you come down consistently with malaria?' You don't want to tell the researcher: 'I am not using a mosquito net'.* (IDI 3)"
Community mobilization will be helpful to allay these fears. During mobilization, women and leaders who had previously participated in research could be invited as peer-mobilizers to reassure other women that no *'side effects'* are associated to the experimental interventions. Some women would agree to participate if they see that *'nothing happened'* to other women or if they see that the chiefs and chairladies consented for their own children to enrol.
Framing gendered norms that could deter participation {#Sec15}
-----------------------------------------------------
Traditional gendered values and how these are used by community members to construct norms on how men and women should interact also need be considered in malaria research planning. Women were described as used to discussing sensitive topics with male midwives and nurses in Monrovia. However, in rural settings, as one *nurse* from Lofa County explained, women could be punished if seen talking to *'strange'* men:"*All the women would be a distance away from the \[male\] strangers. You will never see women with your eyes. Why are the women chased away? That is traditional. If you, a man, touch any woman, they will beat that woman 50 lashes.* (FGD 1)"
Men's attitude to control women might be a barrier for pregnant women to engage in malaria research. Some *women* reported that they asked their partners to allow them to participate in the malaria prevalence study. One *woman* said she wanted to be sure she was not taking any risks. Other w*omen* in an FGD said that many asked for permission because of '*fear'* to their reactions.
For *staff*, *leaders* and *women*, Liberian men are *'jealous', 'authoritarian'* and *'believe in supremacy'* over women. Jealousy was described as an expected *'manifestation of love'*, a demonstration that men are interested in their partners. Thus, some women asked them for permission *'out of love'* because in Liberia women were expected to inform men about their engagement in any outdoor activity. In the opposite scenario of men being targeted as study subjects, no female participant in this study believed that any Liberian man would ever ask permission from his female partner.
The appropriateness of male research staff visiting women participants in their houses, in the scenario of a household-based malaria survey, was discussed. One *leader* elaborated that women would not have any problem but that their *'boyfriends'* could create a *'conflict'*. Some partners may also disagree with women being interviewed by a *'white man'*. As one male *leader* explained, partners will feel that women, if visited by *'young'* or *'white'* men, they *'may find another lover'*. To prevent conflicts, the use of community *'elder men'* as *'surveyors'* was suggested.
Discussion {#Sec16}
==========
Government and academia-led science education, engagement of community leaders in research planning, and transparent information on the benefits that researchers and research institutions accrue from research could be useful strategies to improve pregnant women's acceptance to participate in malaria research in Liberia. However, even if these strategies were adopted, a myriad of sociocultural factors, traditional beliefs and gendered norms could become deterrents for women's actual engagement. If left unaddressed, these deterrents could easily hamper the conduct of research and hinder the transfer of improved prevention and care to the populations most at-risk of malaria.
The same factors that deter uptake of malaria prevention and care for pregnant women intertwine with community members' views on the utility of malaria research. The participants' arguments emphasize the need to address inequity gaps in the healthcare system to ensure that the most vulnerable benefit from the translation of malaria research findings into public health and healthcare provision. Inequity gaps in the healthcare system; low awareness of patients' rights to negotiate care; lack of platforms to denounce violation of patients' rights; paternalism from healthcare workers; and mistrust of healthcare workers were identified as problems that need be urgently addressed. On the other hand, participants' justification of some current practices (i.e. payment for blood to help institutions recover their expenditure in equipment) may reflect the populations' beliefs on how healthcare systems must be financed. Should this be the case, acquiescence of the population to palliate some of these inequity gaps might not be easily gained.
Suspicions, fears and misconceptions must be considered when planning malaria research in Liberia. Based on participants' description of the *'rumours'* that circulated during the Ebola epidemic, future research should include approaches that clearly explain the purpose of collecting bodily specimens, the procedures to collect them, and their destination not only to the participants but also to the communities involved. 'Rumour surveillance' strategies, such as the one implemented by the World Health Organization in 2004 during the avian influenza H5N1 outbreak \[[@CR45]\], could also be useful for mapping doubts and concerns and providing a timely dissemination of accurate information for future health research studies.
Most of the fears and misconceptions described have been reported in other settings. For instance, fear to give blood that could be *'sold'*, used to *'fabricate'* other viruses, or tested for stigmatizing diseases has also been reported in Ghana \[[@CR46]\] and in The Gambia \[[@CR39]\]. Nevertheless, it must be noted that Liberia has not experienced as much malaria research as other West African countries. Current fears and myths gained momentum, according to the participants' narratives, during the conduct of the *'PREVAIL'* (ClinicalTrials.gov Id: NCT02344407) and *'Z*-*Mapp'* (ClinicalTrials.gov Id: NCT02344407) trials \[[@CR23], [@CR27], [@CR28]\]. These were two of the five trials initiated during the Ebola epidemics in Liberia \[[@CR27]\]. Some of the beliefs and rumours reported in this article were already identified and addressed by the PREVAIL investigators at the very outset of the Ebola vaccine trial in Monrovia \[[@CR23]\]. In spite of a social mobilization strategy put in place by the PREVAIL investigators \[[@CR23]\], those fears and myths persist today. Irrespective of the alleged association of these *'rumours'* with the Ebola vaccine trials, their persistence might also be explained by the population's mistrust of health care workers and authorities, and might reflect broader concerns on current political and socio-economical issues. As issues pertaining to inequity and trust are not to be solved in the short-term, future research should not underestimate the possibility that these fears and *'rumours'* may influence the acceptance of malaria research by pregnant women.
Some of the solutions proposed by the participants to improve people's perception of research and to encourage participation have also been reported in other studies, such as the delegation of the explanation of the experimental intervention to local leaders and active mobilization through volunteer peer-education \[[@CR47]\]. Interestingly, whilst previous studies reported on such approaches as effective solutions based on their actual research findings, in this study, the participants made these recommendations drawing upon the public health interventions they had witnessed during the war, post-war and the Ebola crisis. Thus, the possibility to translate site-specific acceptable and culturally-congruent practices from public health to malaria research should not be belittled.
This study has important implications for future research. The expressed possibility of undue inducement into research by means of financial compensation, reprisals from healthcare workers, and therapeutic misconceptions accentuate the vulnerability of pregnant women in this research context \[[@CR34], [@CR37], [@CR48]\]. The possibility that some men may believe that women do not have the right to consent to participate in research on their own \[[@CR37]\], a worrying consideration pointed out by the participants, also needs be tackled. To prevent these hazards, risk--benefit analyses must be performed at the outset of the research. Participatory approaches to research (PAR) in which the targeted communities and their traditional representatives are engaged, are key to put in place mitigation measures. As an example, during the Ebola outbreak, a research using PAR methodologies was conducted in New Kru Town, a low-income neighbourhood in Monrovia, to identify deterrents for pregnant women to seek for labour and delivery care in their government-run maternity referral hospital \[[@CR49]\]. That research, which also engaged healthcare workers, community representatives and pregnant women, proved how PAR was a feasible qualitative approach to improve community members' trust of healthcare workers and also to collaboratively plan strategies to promote healthcare utilization by pregnant women \[[@CR49]\].
All potential barriers to malaria research conduct in Liberia are historically-shaped and relate to a wide range of factors. Looking exclusively at the impact of the Ebola epidemics in populations' attitudes would be an erroneous approach. Fortunately, the participants of this study were able to discuss the different interview topics in the light of political, socio-economical and cultural nuances that transcended the Ebola epidemics. The aim of this study was to provide an accurate 'picture' of the current perceptions that may promote or hinder the pregnant women's participation in malaria research, and not to interpret in depth how the recent history of Liberia is interwoven with this study's findings. However, further socio-historical research could be done to analyse how the US-promoted neoliberal capitalism during the cold war times \[[@CR50], [@CR51]\]; the endemic corruption during the post-war mandate of President Ellen Johnson Sirleaf \[[@CR52]\]; and the implementation of clinical trials during the Ebola outbreak \[[@CR23], [@CR28]\], might have shaped how the Liberians construct notions, meaning and values with regards to health, disease, healthcare and research.
The strength of this study was the use of the feminist grounded theory to identify areas of oppression and vulnerability for women \[[@CR41]--[@CR43]\]. Some of the issues of oppression identified by the participants, such as the need to extend research education to women's partners and the women's fears of being judged by healthcare workers for their uptake of malaria prevention, must be taken into account when planning future malaria research.
A limitation of this study was that a more comprehensive description on the deterrents to engage in malaria research could have been obtained if individuals with no history of engagement in research had been invited. Thus, the possibility that social desirability might have guided the participants' narratives cannot be disregarded. Recall bias might also have also influenced the participants' narratives of past malaria care-seeking and of exposure to trials during the Ebola outbreak. Another limitation was that no discussion was held on the participants' views regarding the exclusion of pregnant women from research to avoid health risks to the foetus. Some participants may have been aware that the trials initiated during the Ebola epidemics excluded pregnant women as participants \[[@CR27]\] and their opinions in that regard might have been very useful to this discussion.
Conclusion {#Sec17}
==========
The participants of this study suggested implementing measures to provide evidence-based malaria and research education to the general population and to engage community leaders in research design, target population mobilization, and local dissemination activities. In agreement with the New Kru Town's PAR study \[[@CR49]\], researchers should consider investing time and financial resources to ensure community support in any strategy aiming at informing pregnant women of the purposes of the malaria research and in soliciting their participation. Benchmarking for acceptable practices used in previous public health campaigns as well as mapping, documenting and understanding implementation and communication errors from previous clinical trials during the Ebola outbreak might help allay fears and misconceptions and encourage pregnant women to engage in malaria research as participants whose rights to wellbeing, autonomy, confidentiality and safety are safeguarded. Importantly, if widespread disempowerment and inequity issues are not tackled, population's lack of trust in the healthcare establishment and in researchers will hinder their acceptance of malaria research, and, importantly, might impede the translation of key novel findings into improved access and use of malaria prevention and therapeutics by the most vulnerable populations attending the Liberian healthcare facilities.
AM and GMP designed the study. GMP collected, processed and analysed the data. BBB, CKT and DPL supported the field research in Liberia. GMP prepared the draft manuscript and MM, AS, ARB, AMG, CKT, BBB, QB and AM revised and contributed intellectually to its preparation for submission. All authors read and approved the final manuscript.
Acknowledgements {#FPar1}
================
We are indebted to all the participants who gave us their time and insights to prepare this publication, and, especially, to two of the St Joseph Catholic Hospital's *staff* participants who demonstrated much enthusiasm towards this study and who, unfortunately, died before we could share the final findings with them.
Competing interests {#FPar2}
===================
The authors declare that they have no competing interests.
Availability of data and materials {#FPar3}
==================================
The datasets generated and/or analysed during the current study are not publicly available due to the need to safeguard the privacy and confidentiality of the participants but are available from the corresponding author on reasonable request.
Consent for publication {#FPar4}
=======================
As part of the informed consent process, all participants in this study gave the research team permission for their data to be recorded, transcribed, anonymised, analysed and used in the preparation of any scientific publication.
Ethics approval and consent to participate {#FPar5}
==========================================
The University of Liberia-Pacific Institute of Research and Evaluation Institutional Review Board (Ref.: 16-08-003; UL-PIRE IRB, Monrovia, Liberia) and the Hospital Clínic Health Research Ethics Committee (Ref.: HCB/2016/0604; CEIC, Barcelona, Spain) gave ethics approval on the study protocol and the consent forms. All participants in this study gave written informed consent. Participation in this study was voluntary.
Participants were free to withdraw from the study at any time. Each participant received written information about the study which was also explained by trained study staff. Sufficient time was given to the participant to decide whether or not to participate in the study. Information sheet and consent form documents were available in English language. All participants in this study gave written informed consent.
Funding {#FPar6}
=======
This study was conducted thanks to a grant from the European and Developing Countries Clinical Trials Partnership (EDCTP) and the World Health Organization Special Programme for Research and Training in Tropical Diseases. The EDCTP2 programme is supported under Horizon 2020, the European Union's Framework Programme for Research and Innovation. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. Alfredo Mayor is supported by the Department d'Universitats I Recerca de la Generalitat de Catalunya (AGAUR; 2017SGR664). The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Publisher's Note {#FPar7}
================
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
| 2023-11-07T01:26:28.774034 | https://example.com/article/5158 |
Chairman expects hemp bill to pass Kentucky House committee Wednesday
Agriculture Commissioner James Comer’s plan to regulate production of industrial hemp — should the federal government allow it — was rejuvenated Monday when the House agriculture committee chairman said he expects his committee “easily” will approve Senate Bill 50 on Wednesday.
But the bill’s future beyond that remained in question after Speaker Greg Stumbo did not commit to having the bill called for a vote by the full House if it passes committee.
“I’m not for the bill,” Stumbo said. “But I don’t think we need it.”
SB 50 would require industrial hemp growers to obtain an annual license from the state agriculture department besides other regulatory requirements.
Stumbo sent a letter Monday requesting an opinion from Attorney General Jack Conway about whether an existing law that says Kentucky’s hemp policy will mirror the federal government’s is sufficient if the federal government allows production of hemp, which currently is classified alongside its higher THC relative marijuana.
“Kentucky has no need for additional state bureaucracy involving permits issued by a state Hemp Czar,” Stumbo, D-Prestonsburg, wrote in his letter.
Comer and other supporters — including most of the state’s federal congressional delegation — argue that passing the regulatory setup would position Kentucky to be among the first states to produce hemp, bringing jobs with the processing plants that would be needed to prepare hemp for manufacturers.
Stumbo is skeptical that the risk of complicating marijuana enforcement is worth the jobs hemp production could bring to the state. Those concerns have been raised by the Kentucky State Police and other law enforcement groups.
Rep. Tom McKee, D-Cynthiana, adjourned a meeting last week after two hours of testimony without taking a vote. He previously wanted his committee to approve substitute language that would have replaced the bill’s regulatory provisions with field trials by the University of Kentucky.
Citing Comer’s claims that hemp will lead to Kentucky jobs, McKee said Monday, “we don’t want to be in the way of that.”
Comer said he isn’t worried that the bill could be bottled up after it passes committee, citing widespread interest in the measure. He said he was asked about it over the weekend at his daughter’s cheerleading competition in Lexington.
“Everyone in Kentucky is watching this bill,” he said.
U.S. Sens. Mitch McConnell and Rand Paul have proposed federal legislation that would distinguish hemp from marijuana, clearing the way for cultivation.
Hemp looks like marijuana and typically contains less than 0.3 percent THC — the active ingredient in marijuana. Marijuana’s THC content is between 3 percent and 15 percent. But both are classified the same under federal drug policy.
The latest Courier-Journal Bluegrass Poll found that 65 percent of Kentuckians favor legalizing hemp for industrial uses, compared to 22 percent opposed and 13 percent unsure. The poll had a margin of error of 3.9 percentage points.
VN:F [1.9.22_1171]
please wait...
Rating: 10.0/10 (2 votes cast)
VN:F [1.9.22_1171]
Rating: +2 (from 2 votes)
Chairman expects hemp bill to pass Kentucky House committee Wednesday, 10.0 out of 10 based on 2 ratings | 2023-08-14T01:26:28.774034 | https://example.com/article/2799 |
Sunday, October 05, 2014
Matt Kemp and Zack Greinke gave us permission to exhale on Saturday night, injecting the Dodgers with a burst of hope by preventing a repeat of a catastrophic Game 1. For Kemp, who hit what would be the game-winning home run in the eighth inning, it was a triumphant high point following two years of rehab and rebuilding after his fateful collision with the Coors Field outfield wall in 2012.
Greinke performed masterfully, settling the frayed nerves of a pitching staff that surrendered 10 runs in Game 1. He pitched seven shutout innings, striking out seven and going 2 for 3 at the plate with a run scored in the third. A.J. stayed hot by starting the inning with a double, followed by a single by Greinke. Dee hit an RBI grounder and Greinke moved to second thanks to Mattingly's successful challenge of Kolten Wong's misplay. After a Puig strikeout (he went 0 for 4), AGon knocked Greinke in.
And that was it until the eighth, when Mattingly replaced Greinke with J.P. Howell, having already gotten lucky by extending Greinke through the seventh. Howell promptly gave up a single then a home run to that motherfucker Matt Carpenter, the score was tied, and Dodger fans were reliving the nightmare.
But Kemp rewrote the ending on the fourth pitch from Cardinals reliever Pat Neshek, Kenley came in for a much-needed 1-2-3 save, and this series is tied 1-1.
Breathe. In. Out. Game 3 is Monday in St. Louis and the Dodgers have a 49-32 road record this year. Breathe. In. Out. | 2024-02-27T01:26:28.774034 | https://example.com/article/3179 |
Monday, November 30, 2009
Pumpkin Pie...yummy.
So my pumpkin pies turned out great. Danny said it was probably the best pumpkin pie he's ever had. That's always nice to hear!
Start with eggs.
Eggs in a bowl. Fascinating!
All the spices you'll need.
I forgot to take a picture of the can of pumpkin. But you use canned pumpkin NOT pumpkin pie filling. We're making this from scratch. The above is Ally helping me mix up the pumpkin with the other stuff. When I dumped the pumpkin into the bowl, Ally said it smelled like carrots.
After the milk and other stuff is added. The filling ends up very runny, but it's supposed to be that way!
Going into the oven. When making this particular recipe, because it's so runny, you need to put the pie plates on the oven rack, then pour the filling in. If you try putting them in the oven after you've filled them, you'll end up spilling it.
Finished pies sitting out to cool. Don't they look nice?
Now to make homemade whipped cream. These are the only two ingredients you'll need. It's really very easy.
Action shot of the mixer. I held the mixer with one hand and the camera with the other to take this. Awesome.
Whipped creamy goodness! Homemade whipped cream is the best.
And finally the finished pie with the little guy from last week perched on top. I just served the whipped cream on the side because some people don't like whipped cream on their pie. Imagine that.
No comments:
Post a Comment
Documenting a beginner's trials and experimentations in cake decorating. Keep in mind I am not a professional! I have had no training whatsoever. All of this is just trial and error. If any of you decorate cakes and can offer any advice or tips, please do so! Any help is always appreciated. Now, follow me as I learn! | 2024-05-06T01:26:28.774034 | https://example.com/article/1586 |
Weightlifting is not just a man’s sport. It’s also a sport for women that tests strength, endurance, and power. But to be effective, a woman has to train hard and to use the best kind of fitness equipment and included are the best weight lifting shoes. This is a review of the best weightlifting shoes for women. This kind of shoes is not your average workout shoes for women.
Lifting shoes for women are made from very strong and durable materials, shaped to fit women’s feet to create that locked-in feeling. It is also breathable and very comfortable, which is important for women who engage in powerlifting, lifting weights for strength training, and also for cross-fit training.
And whether you’re new to using cross fit shoes for women or you’re looking for a better pair of lifting shoes for women, we know you’ll love these awesome weightlifting shoes.
Our Best Weightlifting Shoes For Women
Here we present our selections for the best weightlifting shoes for women. So you can get started right away.
1. Reebok Women’s Legacylifter Sneaker
The Reebok Women’s LegacyLifter Sneaker is a pair that’s designed for powerlifters and weight lifters alike. It is made from leather as well as synthetic materials that are comfortable, breathable. It has a strong and powerful rubber sole that will keep your grip on the floor, especially during training and competition.
The shaft of this sneaker is low top from the arch. It has double straps that you can easily adjust according to your level of comfort. You’ll feel that your feet are locked in and comfortable with these Reebok sneakers.
Check Price
Pros Made from comfortable materials
With a durable and stable rubber sole
Low-top arch
Stable and breathable
With a locked-in feel Cons Complaints that it is too short
Key Features about these shoes:
The Reebok Legacy Lifter for women is a shoe that’s designed for ultimate power, control, and protection during weightlifting, powerlifting, and when weight training.
It is made from durable materials and shaped for precision, and that locked-in feeling needed by weight trainers.
This could be the weightlifting shoes for women you have been looking for.
2.Inov-8 Fastlift 335 Powerlifting Weight Lifting Training Shoes
Available in three color combinations, the Inov-8 Fastlift powerlifting weight training shoes are made from quality 100% synthetic materials. It comes with a rubber sole, which has a good grip and safe to use daily or in a competition. This has a taller heel that measures around 1.25” with a platform of 0.25”. This helps support the entire foot when lifting heavyweights.
Fastlift’s outsole rubber will hold on any type of floor, including gym floors, boxing floors, and cement floors, as you lift heavy types of weight. It has improved stability with its outer heel cage plus Power Truss feature that provides lateral strength and stability, which are again important during powerlifting.
Check Price
Pros Made from durable materials
With a safe and secure sole
Taller heel and platform
Improved stability
Improved design Cons Problems with size
Complaints it’s too firm
Key Features about these shoes:
The Inov-8 Fastlift is a colorful, safe, and comfortable powerlifting or weightlifting shoes for women.
It is designed with a taller heel and platform to enhance lifting form and strength.
It also comes with an improved design that protects the feet and improves grip.
It may be the weightlifting shoes for you.
3. NOBULL Women’s Training Shoes and Styles
This is a pair of women’s training shoes available in more than ten different colors. It is a show that’s perfect for lifting weights and is also for climbing, sliding, running, and grinding. It won’t keep you down because it is designed to be lightweight, flexible, and breathable.
It is made from a one-piece SuperFabric material that is durable, abrasion-resistant, and breathable and has an amazing feel. The SuperFabric guard plates are also applied on the mesh base that shields the shoe well. It is easy to move from an indoor area to an outdoor area when you’re wearing these training shoes.
Check Price
Pros Lightweight shoe that’s breathable
Made from durable materials
Designed to keep your feet safe
Easily transition from outdoors to indoors
Available in different colors Cons Problems with sizing
Complaints that material was too stiff
Key Features about these shoes:
The NOBULL Women’s Training Shoes is a training shoe that’s made for all kinds of activities, not just for weightlifting.
It’s constructed out of a one-piece, durable material that is designed to keep feet comfortable and protected as you perform different activities.
It ensures an easy transition from one environment to another.
It could be the best weightlifting shoes that are perfect for you.
4. Converse Chuck Taylor All Star High Top Sneaker
The Converse Chuck Taylor All-Star has been around since 1917, and over many years, it has become a part of urban fashion. It is made from durable and breathable canvas with a vulcanized rubber sole for improved traction control.
This is very important for weightlifters to ensure that they are safe and secure as they lift powerful weights. It is great for fashion, impressive on the streets and is also great for sports.
Check Price
Pros Made from durable materials
Classic high-top shaft
With a comfortable cushioned insole
Can be worn outside the gym
Available in different colors and designs Cons Not very comfortable for some
Sizing problems
Key Features about these shoes:
The Converse Chuck Taylor is a classic, and it’s not just on the street but also in the gym.
It is a fashionable shoe that’s available in a variety of colors and designs.
It is made from secure materials and is comfortable to wear.
It could be the stylish, classic, yet comfortable, and durable pair of weightlifting shoes that’s perfect for you.
5. Nike WMNS Metcon 5 Women’s Ao2982-004
The Nike Metcon 5 is an all-around fitness and workout shoes. It is designed for stability with a low, wide, and flat heel so you can get a good grip of the floor as you lift weights, or as you train with weights. It comes with a removable insert that will give you enhanced stability as you perform thrusts, squats, and wall balls.
The material used to make this lovely shoe comes with a textured print that improves the style and enhances its weight. This has an improved grip with directional traction that hugs the sides of the show for improved grip when you climb or slide.
Check Price
Pros Low and flat with a wide heel
Hyperlift insert
Lightweight
Durable materials
Enhanced grip Cons Sizing problems
Key Features about these shoes:
Nike Metcon 5 has been designed to provide safe and secure fitness, workout, and weightlifting shoe.
It is stable as it has a wider and flatter heel, and with the removable insert, you will have better stability and improved weight.
It is perfect for women who want to perform better and lift weights more efficiently as long as the right size is considered.
6 Converse Chuck Taylor All Star Shoreline Low Top Sneaker
The Converse Women’s Chuck Taylor All Star is a low-top sneaker but retains the design, color, and classic soul of the regular Chuck Taylor shoe. It is made from textiles, so it’s washable and easy to maintain. It comes with a durable synthetic sole that will keep your feet safe, whether you’re powerlifting or weight lifting.
This is a slip-on sneaker, so it’s easy to wear even when you’re in a hurry. And other features like a fixed no-tie lace makes it safe to use while weightlifting. The collar is elastic, and the eyelets have a unique design.
Check Price
Pros Made from washable textile
Strong synthetic sole
Low shaft with elastic collar
Easy to wear and install
Available in different colors Cons Sizing issues
Key Features about these shoes:
The Converse Women’s Chuck Taylor is a sneaker that’s an update of the classic high-cut Converse sneaker.
But this one is made of durable and easy to maintain materials and is designed to be worn daily anywhere, even in the gym.
It is a good weightlifting shoe for women because its’ stable, easy to wear, and comes with a durable core.
Meanwhile, some users have encountered sizing issues, but despite these.
The Converse Chuck Taylors for women remains a good candidate as the best weightlifting shoe for women.
7. PUMA Women’s Tazon 6 WNs FM Cross-Trainer Shoe
The PUMA Women’s Tazon 6 is a good cross-trainer shoe that’s made from genuine leather and synthetic material. It has a unique, well-designed rubber sole that enhances grip on any kind of surface. The shaft measures the low top from the arch.
You can use this shoe for different activities, whether you’re running, training, weightlifting, or jogging. The PUMA Tazon 6 is available in three color combinations.
Check Price
Pros Made from durable materials
With a stable rubber sole
Ensures safety when lifting weights
Versatile training shoes
Available in different color combinations Cons Sole is too stiff and firm
Sizing problems
Key Features about these shoes:
The Puma Tazon is made from very durable yet comfortable materials.
It has a stable sole and is versatile to use.
It can be used in the gym when training outdoors and for lifting weights.
Some say that it’s too rigid, especially the sole, and some agreed that it needs to be “broken in” before it’s comfortable to wear.
But despite these, the Tazon remains as a good weightlifting shoe for women that you should check out.
8. Nike Women’s WMNS Metcon 3 Trainers
The Nike Women’s Metcon 3 trainer is made from synthetic material with a safe rubber sole. It comes with Flywire tech. That integrates the shoelaces from the midfoot to create a great fit. This locks your foot in place but won’t affect the foot’s natural movement.
The design is dual-density with a drop-in style midsole, which makes the shoe firmer so it can handle the pressures of heavy lifting or powerlifting. Also, the design features a more comfortable forefoot for enhanced comfort when you walk, run, or jog.
It won’t easily wear or tear as all the high-wear areas of the shoe are covered with an embroidered TPU layer.
Check Price
Pros Flywire technology
Can handle the pressures of lifting
Flexible and comfortable
Won’t easily wear or tear
Soft and perfect for any sport Cons Complaints that these were too tight
Problems with sizing
Key Features about these shoes:
The Nike Metcon 3 is a pair for weightlifting, powerlifting, cross-fit, and for indoor or outdoor training.
It is available in a wide variety of colors and color combinations and is made from very durable materials.
Comfortable and cushions well despite some complaints that it is too tight or some problems with sizing.
The Metcon 3 from Nike may just be the weightlifting shoes you’re looking for.
9. Reebok Women’s CROSSFIT Nano 8.0 Flexweave Cross Trainer
The Reebok CROSSFIT Nano 8.0 is a cross-trainer shoe that can also be used for weightlifting. It is made from tough fabric or textile with a sturdy rubber sole. The shaft is designed to be low-top from the arch, making it easier to walk, jump, jog, or to lift weights.
It is made from a very strong yet lightweight material that’s enhanced with Flexweave tech. This new feature makes the shoe more flexible and stable for any sport.
Aside from the strong material, it is designed with enhanced foot support. The heel bootie design with additional cushions makes this more comfortable. It also comes with Toe Tection with added durability during workouts. Finally, its low cut style enhances ankle mobility so you can train, move, and workout all day.
Check Price
Pros Made from the durable yet lightweight material
Flexible and stable
Comfortable to use in different activities
Low cut design High-performance shoes Cons Complaints that it’s too flat
Sizing problems
Key Features about these shoes:
The Reebok Women’s CROSSFIT Nano 8.0 is a weightlifting shoe that’s also great for cross-fit activities, for indoor or outdoor workouts and other exercises.
It is made from durable materials and comes with several colors and color combinations.
It is comfortable, sturdy, and lightweight.
It may not be for all women since most complained it was too flat.
But despite this and other flaws, it’s still worth checking out as a weightlifting shoe for women.
10. Adidas Women’s Powerlift 4 Cross Trainer
The Adidas Women’s Powerlift 4 is a shoe that’s designed for cross-training and is also great for powerlifting or weightlifting. It is made from 100% textile or fabric and very durable synthetic materials.
It also comes with a flat rubber sole save for a honeycomb design. It comes with a high platform to add stability and comes with a narrow fit, convenient lace closure, and a strap that secures the feet.
Check Price
Pros Made from very durable materials
With a rubber sole
High platform
With a lock-down feel
Lace closure with a Velcro strap Cons Not for people with narrow feet
Sizing problems
Key Features about these shoes:
The Adidas Women’s Powerlift 4 is a pair made from synthetic materials and with a rubber sole that makes it very durable yet comfortable when used.
It is a cross-trainer shoe but will also work well for people who indulge in weightlifting and powerlifting.
And despite some flaws, this remains a good pair for weightlifting practices or competition for women.
What to look for the best weightlifting shoes for women?
When you go shopping like best women’s watches, the best weightlifting shoes for women, consider the following:
Stability
The drop heel in weightlifting shoes provides stability. This style also helps avoids turning your ankles and enhances your hold on the floor.
Check the drop height
This is the drop in elevation from the heel and the toe from the shoe’s insole. When the heel is elevated, the shoe becomes more stable, and you can squat down with ease. Also, this optimizes physical exertion and increases your upward force.
The best fit
Just like any shoe, a weightlifting shoe has to fit well. Also, a well-fitting shoe will help you focus and will avoid distractions because of a painful foot. Settle for a snug fit without the feeling of pinching your toes or the top of the foot. It should also be wide enough to accommodate the spreading of the foot, which happens when you lift heaving weights.
Good value
Value means different from one person to another, but it could be anything like improved stability, great comfort, and good performance. And this is simply a natural thing when it comes to wearing the shoe.
The benefits of wearing the best weightlifting shoes for women
Still unsure if a weightlifting shoe is for you; check out the following benefits of this type of shoe
Provides better stability for weightlifters
With weightlifting shoes, your feet will be more stable when you pull weights, and you will stay safe as you perform different routines.
Enhances flexibility
This type of show enhances your flexibility, lets you take the pressures of weightlifting, and keeps you in great shape before, during, and after your routines.
For a more comfortable fit
Weightlifting demands concentration. Even a small thing like an ill-fitting shoe or a shoe that feels too tight can cost your performance. You need a very durable shoe for practice, training, and during the competition as well.
FAQ
When do you need to wear weightlifting shoes?
You should wear weightlifting shoes if you plan to engage in weight training or weight lifting activities. Take note that wearing other types of shoes may affect your performance, concentration, and versatility. Also, weightlifting shoes should be worn during training and competition.
Why use a flat shoe for lifting things?
Weightlifting shoes may come with curved soles to enhance support for walking and running, but it’s best to use a flat shoe to improve support because it’s easier to push from the ground during routines like deadlifts and squats.
When you’re lifting things, a rigid or flat sole is better so the heel can press on the ground or floor during routines like squats as well as deadlifts. You can’t have strong feet if you use running shoes for weightlifting.
Can you lift weighs barefoot?
Lifting things like weights barefoot can enhance grip, power, and mobility; however, your ankle has less support. Also, you can’t use weights while barefoot in a gym because this is considered unhygienic. You may use weights barefoot if you want to train at home, but it’s better to wear weightlifting shoes instead.
Are wearing weightlifting shoes a form of cheating?
You can lift better with weightlifting shoes with higher heels, and it’s not considered cheating to do so. If you’re a part of a competition and you’re unsure if a weightlifting shoe with higher heels is not permitted, talk to the committee in charge to find out before you compete.
Do you need to use squat shoes aside from weightlifting shoes?
Most trainers and experts agree that if you are not into improving your overall performance, then you may not use squat shoes. But if you want to enhance your routines and lift weights regularly, then you should choose a durable, versatile and comfortable weightlifting shoe.
What’s the difference between a weightlifting shoe for women and shoes for men?
Men’s shoes are larger and wider because their feet are larger and wider as well. Women’s shoes are smaller and slender, and this is because their feet are also naturally smaller and more slender than a man’s.
Final Verdict
From our list of the ten best weightlifting shoes for women, we choose the Reebok Legacy Lifter. There are many reasons why Legacy Lifter is the best. First, it is designed for ultimate power, control, and protection, especially in activities like weightlifting, powerlifting, and when weight training.
This shoe is made from durable materials and is designed for precision and that locked-in feeling because of its secure locking design. It is a weightlifting shoe that’s available in different sizes, and thus you can easily choose the best one for you.
And despite some flaws, we still recommend the Legacy Lifter for safe, efficient, and reliable weight lifting activities. If you think that the Reebok Legacy Lifter is the right weightlifting shoe for you, check this product out from this link. | 2023-10-10T01:26:28.774034 | https://example.com/article/1343 |
Get in touch with REMED
FAQ
QALL【TMS / TAMAS】 Q1) How should the treatment be performed when there are complex symptoms (Example: depression & anxiety)?
A
A) It is common for 2 symptoms to appear at the same time. In this case, priority is given to the symptom that is thought to be the more serious of the two, and simultaneous undertaking or changing the protocol is advisable while observing the progress.
QALL【TMS / TAMAS】 Q2) Can TMS treatment be performed when there is an abnormality in the brain (cerebral hemorrhage, brain tumor, etc.)?
A
A) In general, at a medium or large-sized hospital, an abnormality of the brain such as cerebral hemorrhage, or cerebral infarction, and so forth can be judged in advance; however, in a smaller clinic, the patient would be relied on for this information. Therefore, if there is an abnormality of the brain, TMS treatment is generally not recommended.
QALL【TMS / TAMAS】 Q3) What is an appropriate distance between the transducer and the patient’s head or cranium?
A
A) The strength of the magnetic field decreases as the distance from the transducer is increased. It is recommendable to conduct the treatment by attaching the transducer to the skin, without any gap.
QALL【TMS / TAMAS】 Q4) Is it correct to say that one should apply high frequency stimulation to the left brain, and low frequency stimulation to the right brain?
A
A) In the initial stages of experimentation with this treatment, left brain stimulation and right brain stimulation were divided. But more recently, this has no longer been the general practice as it is known that almost identical effects are realized through applying stimulation to either side.
QALL【TMS / TAMAS】 Q5) Are protocols established for each disease?
A
A) Numerous studies have been conducted on TMS treatment. The treatment protocol for depression is fairly well-determined and is close to approval from the FDA (USA); however, protocols for Tic disorder, headache, and the like are still under investigation. Nevertheless, there are protocols that are currently being used at the clinical level.
QALL【TMS / TAMAS】 Q6) Is there stimulation when conducting the treatment?
A
A) Of course, yes. The patient may feel pain and be startled due to the unfamiliar stimulation from the initial feeling of stimulation and invisible brain stimulation treatment. However, as it is not a significant amount of pain that cannot be endured, it poses no barrier to treatment. In addition, there is a tendency for healthy individuals to have a more sensitive response.
QALL【PAIN THERAPY - SALUS TALENT】 Q1) Can it be used for the area of the body with artificial joints or plate pins?
A
A) Due to the nature of the magnetic field deep heat will be generated, which may cause deep-seated burns.
QALL【PAIN THERAPY / SALUS TALENT】 Q2) Is it the same effect to use on clothes?
A
A) One of the characteristics of a magnetic field is that it is permeable with a similar therapeutic effect. Therefore, it can be used on clothes.
QALL【PAIN THERAPY / SALUS TALENT】 Q3) Are there any precautions when using on clothes?
A
A) If there is a metallic decoration on the clothes, the magnetic field may cause burns on the surface of the skin. (e.g., bra strap rings, underwear metal ornaments, metal-containing fibers).
QALL【PAIN THERAPY / SALUS TALENT】 Q4) How much power is consumed?
A
A) An amount of power to operate the small heater is generally consumed (Max. 1.5 kW)
QPRODUCT【TMS / TAMAS】 Q1) How should the treatment be performed when there are complex symptoms (Example: depression & anxiety)?
A
A) It is common for 2 symptoms to appear at the same time. In this case, priority is given to the symptom that is thought to be the more serious of the two, and simultaneous undertaking or changing the protocol is advisable while observing the progress.
QPRODUCT【TMS / TAMAS】 Q2) Can TMS treatment be performed when there is an abnormality in the brain (cerebral hemorrhage, brain tumor, etc.)?
A
A) In general, at a medium or large-sized hospital, an abnormality of the brain such as cerebral hemorrhage, or cerebral infarction, and so forth can be judged in advance; however, in a smaller clinic, the patient would be relied on for this information. Therefore, if there is an abnormality of the brain, TMS treatment is generally not recommended.
QPRODUCT【TMS / TAMAS】 Q3) What is an appropriate distance between the transducer and the patient’s head or cranium?
A
A) The strength of the magnetic field decreases as the distance from the transducer is increased. It is recommendable to conduct the treatment by attaching the transducer to the skin, without any gap.
QPRODUCT【TMS / TAMAS】 Q4) Is it correct to say that one should apply high frequency stimulation to the left brain, and low frequency stimulation to the right brain?
A
A) In the initial stages of experimentation with this treatment, left brain stimulation and right brain stimulation were divided. But more recently, this has no longer been the general practice as it is known that almost identical effects are realized through applying stimulation to either side.
QPRODUCT【TMS / TAMAS】 Q5) Are protocols established for each disease?
A
A) Numerous studies have been conducted on TMS treatment. The treatment protocol for depression is fairly well-determined and is close to approval from the FDA (USA); however, protocols for Tic disorder, headache, and the like are still under investigation. Nevertheless, there are protocols that are currently being used at the clinical level.
QPRODUCT【TMS / TAMAS】 Q6) Is there stimulation when conducting the treatment?
A
A) Of course, yes. The patient may feel pain and be startled due to the unfamiliar stimulation from the initial feeling of stimulation and invisible brain stimulation treatment. However, as it is not a significant amount of pain that cannot be endured, it poses no barrier to treatment. In addition, there is a tendency for healthy individuals to have a more sensitive response.
QPRODUCT【PAIN THERAPY - SALUS TALENT】 Q1) Can it be used for the area of the body with artificial joints or plate pins?
A
A) Due to the nature of the magnetic field deep heat will be generated, which may cause deep-seated burns.
QPRODUCT【PAIN THERAPY / SALUS TALENT】 Q2) Is it the same effect to use on clothes?
A
A) One of the characteristics of a magnetic field is that it is permeable with a similar therapeutic effect. Therefore, it can be used on clothes.
QPRODUCT【PAIN THERAPY / SALUS TALENT】 Q3) Are there any precautions when using on clothes?
A
A) If there is a metallic decoration on the clothes, the magnetic field may cause burns on the surface of the skin. (e.g., bra strap rings, underwear metal ornaments, metal-containing fibers).
QPRODUCT【PAIN THERAPY / SALUS TALENT】 Q4) How much power is consumed?
A
A) An amount of power to operate the small heater is generally consumed (Max. 1.5 kW) | 2023-09-04T01:26:28.774034 | https://example.com/article/4267 |
Big ‘Star Wars’ Announcement Teased for 40th Anniversary
Star Wars Celebration is set to kick off in just a few days, and with the 40th anniversary of the iconic franchise on the horizon, fans are expecting this year’s festivities to be extra special — but it looks like we won’t have to wait until later this week for major news from a galaxy far, far away. Good Morning America is teasing a big Star Wars announcement for tomorrow’s episode, but what could it possibly be? The first teaser for The Last Jedi? A revelation about one of your favorite characters?
We’ll have to wait until tomorrow morning to find out, but the official Good Morning America Twitter account has us on pins and needles:
Daisy Ridley and Mark Hamill will appear on Good Morning America to deliver an announcement “40 years in the making” — that phrasing is certainly intriguing, and conjures up all sorts of ideas. The most obvious assumption is a sneak peek at The Last Jedi, or the reveal of some significant new plot information regarding Luke and Rey.
But then there’s the line, “You’ll wanna be a part of this FORCE,” with the emphasis on “force,” which leads me to suspect that, in addition to whatever is actually revealed, Ridley and Hamill may also unveil a new Force for Change promotion that ties into the release of The Last Jedi. Force for Change, for those unaware, is Lucasfilm and Disney’s official Star Wars-themed charity, which spreads awareness and raises funds for global issues. That’s my guess.
Luckily, we won’t have to wait long to see what these two are up to — we’ll just have to get up bright and early to do so.
Star Wars: The Last Jedi is directed by Rian Johnson and hits theaters on December 15, 2017. | 2024-01-08T01:26:28.774034 | https://example.com/article/5473 |
Introduction {#Sec1}
============
The mechanical properties of the extracellular matrix (ECM), especially stiffness, have been shown to regulate a gamut of cellular processes including cell proliferation, migration and differentiation^[@CR1],[@CR2]^. In addition, disease states are often associated with increase in ECM stiffness, as reported in multiple cancers^[@CR3]^. In breast cancer, increased deposition of collagen I and its crosslinking induces a nearly 10-fold stiffening of the mammary stroma^[@CR4]^. Increase in ECM stiffness is associated with formation of stable adhesions, increased cell spreading and motility, increase in generation of cell-substrate traction forces, and increase in cell stiffness^[@CR5]^. Cancer invasion through these dense matrices is associated with matrix-metalloproteinase (MMP)-mediated ECM degradation generating paths for migration^[@CR6]--[@CR8]^. Seminal work by Weaver and co-workers has shown that increase in ECM stiffness causes increased invadopodia-mediated ECM degradation, thereby establishing a link between increased ECM density and cancer invasiveness^[@CR9]^.
In addition to ECM degradation, MMPs play diverse roles in regulating cell behavior. For example, it has been shown that outside-in signaling mediated by membrane anchored MT1-MMP is critical for regulation of the fate of skeletal stem cells^[@CR10]^. The transmembrane/cytoplasmic domain of MT1-MMP has been also shown to interact with integrin β1 and regulate mammary morphogenesis via the MAPK pathway^[@CR11]^. Remarkably, lack of MT1-MMP catalytic activity induced cytoskeletal and nuclear defects in fibroblasts and caused cellular senescence^[@CR12]^. In melanoma cells, MMP 9 was shown to bind to CD44 and drive protease-independent migration through modulation of cell contractility^[@CR13]^. MMPs have also been implicated in regulating matrix contraction by fibroblasts and keratinocyte migration during wound healing^[@CR14],[@CR15]^. Together, these results highlight the diverse functions of MMPs in regulating cell behavior. However, outside of ECM degradation, the extent to which MMPs regulate cell biophysical properties relevant to invasion, remains incompletely understood.
In this study, we have probed the role of MMP catalytic activity in regulating ECM stiffness-dependent mechanoadaptation responses. Using less invasive MCF-7 cells, and highly invasive MDA-MB-231 and HT-1080 cells, we illustrate the role of MMP catalytic activity in regulating cell mechanics in the invasive cancer cells. We first show ECM stiffness modulates MMP activity in MDA-MB-231 and HT-1080 cells, but not in MCF-7 cells. Inhibition of MMP activity in the invasive cells by the broad spectrum MMP inhibitor GM6001 leads to loss of cell spreading and migration, suppression of traction forces, and cortical softening. These effects are induced by altered localization and expression of integrins, and decrease in phosphorylated focal adhesion kinase (FAK). Re-establishment of normal cell spreading on MMP-pre-conditioned substrates even in the presence of GM6001 illustrates the role of MMP catalytic activity in mediating ECM stiffness-dependent responses in highly invasive cancer cells via modulation of integrins.
Materials and Methods {#Sec2}
=====================
Cell culture {#Sec3}
------------
MCF-7, MDA-MB-231 and HT-1080 cancer cell lines were obtained from National Center for Cell Science (NCCS) (Pune, India) and cultured in high glucose Dulbecco's Modified Eagle Medium DMEM (Invitrogen, Cat \# 11965084) containing 10% fetal bovine serum (FBS, Hi-media, Cat \# RM9952) and maintained at 37 °C at 5% CO~2~ humidified atmosphere. Cells were maintained in 60 cm^2^ culture dishes (Tarsons) and passaged when 80--90% confluent using 0.25% trypsin-EDTA (Hi-media, Cat \# TCL099). For culturing MCF-7 breast cancer cells, human recombinant insulin (Hi-Media, Cat \# TC190) was added to the medium at a concentration of 0.01 mg/ml. For experiments, cells were first synchronized in serum free media for 18--20 hrs. prior to seeding. Further, all experiments were performed at 2% FBS concentration.
Polyacrylamide gel (PA) preparation and ECM coating {#Sec4}
---------------------------------------------------
Studies were performed with polyacrylamide gels (PA) of increasing stiffness. Gels were polymerized on circular glass coverslips of either 12 mm, 18 mm or 22 mm (Blue-star), as described elsewhere^[@CR16]^. For functionalization, Sulfo-SANPAH (Thermo-scientific, Cat \# 22589) at a concentration of 0.1 mM in 50 mM HEPES buffer (SRL chemicals, Cat \# 63732) was added onto the surface of PA gels for 30 min under UV light at 360 nm. Gels were washed 3 times with 50 mM HEPES, and then collagen type I from rat tail (Sigma, Cat \# C3867) dissolved in 1x phosphate buffer saline (PBS) was added at a concentration of 1 µg/cm^2^ overnight at 4 °C to obtain uniform surface coating.
Cell spreading and 2D motility experiments {#Sec5}
------------------------------------------
For stiffness dependent cell responses, cells were cultured on PA gels at a seeding density of 2 × 10^3^ cells/cm^2^ for 12-15 hrs. For cell spreading measurements, cells were fixed with 4% paraformaldehyde (PFA) (Sigma, Cat \# 158127) and then stained for F-actin and nucleus using fluorescently labeled phalloidin (Invitrogen, Cat \#s A-12379, A-34055) and DAPI (4′, 6-diamidino-2-phenylindole, Sigma, Cat \# D9542). Fluorescent images of F-actin and nucleus were acquired using inverted microscope (Olympus IX71) at 20x magnification. Quantification of spreading analysis was done using Fiji-Image J software. Briefly, after background subtraction, images were thresholded and then cell spread area were obtained using the ImageJ-Analyze Particle tool. For probing the effect of MMPs on cell spreading, cells were allowed to adhere on to the gels for 20 mins, after which GM6001 (Abcam, Cat \# ab120845) was added at a concentration of 10 μM for 12--15 hrs. Untreated cells and DMSO (MP biomedical, Cat \# 02196055) treated cells served as controls. For integrin blocking experiments along with cells, RGD peptide (Sigma, Cat \# G4391) at 0.2 mg/ml conc. was added in the media and incubated for 12--15 hrs. For 2D motility experiments, motility videos were acquired after 8 hrs of incubation. Time lapse imaging was performed for every 10 mins for 3 hrs duration using a temperature and CO~2~ control stage (Nikon Eclipse Ti, 20x objective). Cell speed was measured using the manual tracking plugin in Fiji-ImageJ. Directionality ratio was measured from the individual cell trajectories as described elsewhere^[@CR17]^.
Immunocytochemistry (ICC) {#Sec6}
-------------------------
For immunostaining, cells were fixed after 12 hrs of culture using 4% PFA in 1x PBS for 20--25 mins, washed 3 times with 1x PBS solution to removes traces of paraformaldehyde, and permeabilized with 0.1% Triton-X 100 (Sigma, Cat \# 93443) in 1x PBS solution for 3 mins. Cells were blocked with 2% BSA (Sigma, Cat \# A2058) for 45 mins at room temperature (RT) before being incubated with one of the following primary antibodies overnight at 4 °C: anti-vinculin mouse monoclonal antibody (Abcam, Cat \# ab18058), anti-integrin β1 rabbit polyclonal antibody (Abcam, Cat \# ab155145) and anti-integrin β3 rabbit polyclonal antibody (Abcam, Cat \# ab75872). The following day, cells were washed 3 times with 1x PBS and then incubated with one or more of the following secondary antibodies at room temperature (RT) for minimum 1--2 hrs: Alexa-fluor 488 anti-mouse IgG (Invitrogen, Cat \# A-32723), Alexa-fluor 555 anti-rabbit IgG (Invitrogen, Cat \# A-21422). Nuclei were stained with DAPI for 15 mins at RT. Finally, after washing, cells were mounted on glass-slides using Eukitt quick-hardening mounting medium (Sigma, Cat \# 03989). Cells were imaged at 63x magnification using Scanning Probe Confocal Microscope (Zeiss, LSM 780) for probing integrin β1 and integrin β3 localization at cell membrane and for visualizing vinculin-stained focal adhesions. Quantification of number and size of focal adhesions (FAs) is detailed in Supplementary Method Section.
Western blotting {#Sec7}
----------------
For westerns, cells were lysed using RIPA buffer (Sigma, Cat \# R0278) mixed with cocktail of protease and phosphatase inhibitors (Sigma, Cat \# MSSAFE). Protein concentration of cell lysates were determined using Bradford assay. After loading equal amount of protein per lane, SDS-PAGE was performed. The proteins were transferred onto 0.22 μm nitrocellulose membranes (PALL Life Sciences, Cat \# 66485) under ice-cold condition. Following transfer, the membranes were blocked using either 10% BSA (Sigma, Cat \# A2058) or 5% skimmed milk powder (Hi-media, Cat \# GRM1254) in 1x TBST (Tris-Buffered Saline and Tween-20) for 1 hr at RT, and incubated with the following primary antibodies overnight at 4 °C under mild shaking condition: anti-integrin β1 rabbit monoclonal antibody (Abcam Cat \# ab155145), anti-integrin β3 rabbit polyclonal antibody (Abcam, Cat \# ab75872), anti-phospho-FAK^Y397^ rabbit monoclonal antibody (Sigma, Cat \# F7926), anti-β-tubulin rabbit polyclonal antibody (Abcam, Cat \# ab6046), anti-β-actin mouse monoclonal antibody (Abcam, Cat \# ab8226). After washing three time with 1x TBST, membranes were incubated with one of the following secondary antibodies at RT for 1 hr: HRP-conjugated anti-Rabbit IgG (Abcam, Cat \# ab6721) and HRP-conjugated Anti-Mouse IgG (Abcam, Cat \# ab6789). Subsequently, after washing 3 times with 1x TBST, blots were developed on X-ray films (Kodak) using a chemiluminiscent ECL kit (Pierce, Cat \# 32106). Quantification of immunoblots were performed using the densitometric tool of Fiji-ImageJ software.
Gelatin zymography {#Sec8}
------------------
For zymography experiments, cells were cultured on soft and stiff PA gels at a seeding density of 3 × 10^3^ cells/cm^2^. Conditioned media (CM) was collected after 30 hrs of culture, and concentrated using a protein concentrator (PALL Life Sciences, Cat \# MAP010C37) of 10 kDa cut-off. Zymography was performed using 8% SDS-PAGE co-polymerized with 1.5 mg/ml gelatin (Sigma, Cat \# G2500). For experiments, equal amount of protein was loaded per condition and the gels were run under ice cold condition. After running, the gels were incubated with 1x renaturation buffer (2.5% Triton X-100 in distilled H~2~O) for 45 min, and equilibrated with 1x developing buffer (50 mM Tris-base, 50 mM Tris-HCL, 0.2 mM NaCl, 5 mM CaCl~2~, distilled H~2~O and pH adjusted to 7.8--8) for 45 min at RT. Next, gels were dipped in 1x developing buffer, incubated inside water bath maintained at 37 °C for minimum 20 hrs, and then stained with Coomassie Brilliant Blue (0.5% in H~2~O) till clear bands (representing protease activity) were observed. Densitometric quantification of secreted MMP levels was performed using Fiji-ImageJ software.
Atomic Force Microscopy (AFM) {#Sec9}
-----------------------------
For measuring stiffness of cells and gels, pyramidal AFM probes of nominal spring constant 30 pN/nm (10 kHz, Cat \# TR400PB, Olympus) were used. Exact values of cantilever stiffness were obtained using thermal calibration method. For obtaining estimates of PA gel stiffness, indentation curves were fitted till 2000 nm using Hertz model for pyramidal probe:$$\documentclass[12pt]{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\usepackage{upgreek}
\setlength{\oddsidemargin}{-69pt}
\begin{document}$${\boldsymbol{F}}{\boldsymbol{=}}\frac{{\bf{3}}}{{\bf{4}}}{\boldsymbol{\times }}{\bf{E}}\,\frac{{\bf{\tan }}({\boldsymbol{\alpha }}){{\boldsymbol{\delta }}}^{{\bf{2}}}}{({\bf{1}}{\boldsymbol{-}}{{\boldsymbol{\vartheta }}}^{{\bf{2}}})}$$\end{document}$$where, ***F*** represents the indentation force, ***E*** is the elastic modulus of the material, ***α*** is tip half angle, ***δ*** is indentation depth and ***υ*** is Poisson ratio of the elastic material (assumed to be 0.45 for cells and 0.5 for gels)^[@CR18]^. For stiffness measurements, cells were cultured on stiff PA gels in the absence (i.e., DMSO only) and presence of GM6001 for 12--15 hrs duration. For measuring cell cortical stiffness, cells were probed slightly off their center to get the best estimate of cortical stiffness, and the first 500 nm of indentation data was fit using the above Hertz model.
Adhesion experiments {#Sec10}
--------------------
For AFM based RGD-integrin binding measurements, cells were cultured on stiff PA gels in the absence (i.e., DMSO only) and presence of GM6001 for 12--15 hrs duration. Spherical probes (67 kHz, Novascan), 4.5 μm in diameter were coated with 10 μg/ml solution of poly-L-lysine (Sigma, Cat \# P4707) for 20 mins and then treated with 0.5% glutaraldehyde (Sigma, Cat \# G7651) for 20 mins^[@CR19]^. Next, probes were dipped in 0.1 mg/ml solution of RGD peptide (Sigma, Cat \# G4391) for 30 mins, washed 3--4 times in distilled H~2~O, and then dried in a vaccum dessicator for 30 mins. After tip calibration using thermal noise method, RGD-integrin binding studies were performed. While indenting, probe was held at the cell surface for 10 secs to allow formation of integrin-RGD bonds, and then retracted at a tip speed of 3--4 μm/sec. Analysis of maximum adhesion force was performed using Igor Pro 6.22 A software.
Traction force Microscopy (TFM) {#Sec11}
-------------------------------
For TFM studies, cells were seeded sparsely (1000 cells/cm^2^) on collagen coated stiff PA gels co-polymerized with 1 μm fluorescent beads (Sigma, Cat \# L9654), and cultured in the absence (i.e., DMSO only) and presence of GM6001 for 12--15 hrs duration. Images of beads were acquired at 20x magnification (using a Nikon Eclipse Ti inverted microscope) before and after bursting cells using 0.1% Triton X-100 in H~2~O. Data analysis was done using custom written codes in MATLAB 7.8 as described elsewhere^[@CR20]^.
Preparation and characterization of 3D collagen gels {#Sec12}
----------------------------------------------------
For collagen gel preparation, high protein collagen type I solution (Corning, Cat \# 354236) was mixed with 10x PBS kept at 4 °C. Next, ice cold plain DMEM was added and pH was adjusted to 7.2--7.4 using 1 N NaOH solution. After adjusting pH, collagen gel mixture was kept on ice for 10 mins, then 2 × 10^3^ cells were mixed with collagen gel mixture and immediately kept inside CO~2~ incubator for 1 hr. to allow gel formation. After that 10% DMEM was added and allowed the cell to acclimatize for minimum 4 hrs inside CO~2~ incubator. Then, time lapse movies of untreated, DMSO treated, GM6001 treated (10 µM) cells inside collagen gel were captured for 12 hrs at 20 mins interval using temperature and CO~2~ controlled stage (Nikon Eclipse Ti, 10x objective). Cell speed and directionality ratio was obtained as mentioned above. For characterization, collagen hydrogels were snap frozen with liquid N~2~ mounted on the Cryo-unit (PP3000T, Quorum) and fractured with a blade. The frozen samples were then sputter coated with a thin layer of platinum, and Cryo-SEM images obtained with a JSM-7600F FEG-SEM with an acceleration voltage of 5 kV. Pore area of hydrogels was quantified by using Analyse-particle tool of Fiji-ImageJ software.
Statistics {#Sec13}
----------
For statistical analysis, data was first tested for normality using Kolmogorov-Smirnov normality test in Origin 9.1. Based on the outcome of the normality tests, either parametric or non-parametric statistical test were performed. For parametric data, one-way ANOVA/two-way ANOVA was performed to assess statistical significance, and Fisher post-hoc test was used to compare the means. For non-parametric data, Kruskal-Wallis ANOVA/Mann-Whitney test was performed. All statistical analysis was performed using Origin 9.1 with *p* value \< 0.05 considered to be statistical significant.
Results {#Sec14}
=======
MMP activity is essential for eliciting ECM stiffness-dependent responses in invasive cancer cells {#Sec15}
--------------------------------------------------------------------------------------------------
Most epithelial cancers are associated with increase in ECM stiffness driven by increased deposition and crosslinking of collagen I^[@CR21]^. Since increase in ECM stiffness has been associated with increased invasiveness^[@CR22]^, we hypothesized that ECM stiffness positively regulates MMP activity. To test this, experiments were performed on collagen-coated soft (0.46 kPa) and stiff (4.6 kPa) PA gels (Supp. Figure [1A,B](#MOESM1){ref-type="media"}) using the less invasive MCF-7 cells (henceforth MCF7)^[@CR23]^ and two highly metastatic cell lines (MDA-MB-231 and HT1080 (henceforth MDAMB and HT, respectively) (Fig. [1A](#Fig1){ref-type="fig"}). MMP activity on these gels was assessed using gelatin zymography using conditioned media collected from cells cultured on the gels for 30 hrs. Zymography revealed stiffness-dependent increase in MMP 2 and MMP 9 activity in MDA and HT cells; in contrast, in MCF7 cells, very low MMP activity was detected (Fig. [1B](#Fig1){ref-type="fig"}).Figure 1Influence of MMP inhibition on stiffness-dependent cell spreading. (**A**) MCF-7, MDA-MB-231 and HT-1080 cells were cultured sparsely on collagen type I-coated soft and stiff polyacrylamide (PA) hydrogels for desired time duration. (**B**) Assessment of stiffness-dependent activity of matrix metalloproteinases (MMPs) (MMP 2, and 9) using gelatin zymography. Conditioned medium was collected after 30 hrs of incubation. Densitometric quantification of secretion levels of soluble MMPs in conditioned media by MCF-7, MDA-MB-231 and HT-1080 cells seeded on soft and stiff substrates reveals increase in MMP activity on stiffer gels (*n* = 2). (**C**) Representative F-actin (green) and DAPI (blue) stained images of untreated, DMSO treated and GM6001 treated MCF-7, MDA-MB-231, and HT-1080 cells seeded on soft and stiff gels. Scale bar = 50 μm. (**D**) Quantitative analysis of cell spreading of untreated, DMSO treated and GM6001 (GM) treated MCF-7, MDA-MB-231 and HT-1080 cancer cells seeded on soft and stiff gels (*n* = 2--3, at least 90--140 cells per condition). Stars denote statistical significance (\*\*\*p \< 0.001, **ns**: not significant). Statistical significance was determined using Kruskal-Wallis ANOVA/Mann-Whitney test. Error bars represent standard error of mean (±SEM).
To next probe the influence of stiffness-dependent increase in MMP activity on stiffness-dependent cell spreading, experiments were performed with untreated cells, vehicle treated cells (DMSO), and cells cultured in the presence of the broad spectrum MMP inhibitor GM6001 (GM). Cell spreading was assessed after culturing on PA gels for 12--15 hrs. On soft gels, all the three cell types cells exhibited rounded morphology consistent with previous studies^[@CR24]^, with GM treatment having no effect (Fig. [1C,D](#Fig1){ref-type="fig"}). While cell spreading increased on the stiff gels, GM treatment significantly suppressed cell spreading of invasive MDAMB and HT cells, with \~40% drop in spreading of MDAMB cells and \~50% drop in spreading of HT cells. In contrast, there was no significant change in MCF7 cell spreading. Collectively, these results suggest that ECM stiffness-induced increase in MMP activity is essential for cell spreading of MDAMB and HT cells on stiff gels.
MMP activity regulates cell adhesion and motility {#Sec16}
-------------------------------------------------
To probe the mechanism by which MMP inhibition leads to reduction in cell spreading, cells on stiff gels were stained for the focal adhesion protein (FA) vinculin (Fig. [2A](#Fig2){ref-type="fig"}). Quantitative analysis of the number and size of focal adhesions (method of quantification detailed in Supp. Methods and Supp. Figure [2](#MOESM1){ref-type="media"}) revealed that GM treatment led to reduction in both size and number of FAs in MDAMB and HT cells, but not in MCF7 cells (Fig. [2B,C](#Fig2){ref-type="fig"}). Taking the product of the average FA number and the average FA size allowed us to compare the total focal adhesion area in untreated, DMSO treated and GM treated cells. Quantification revealed \~40--50% drop in in GM treated cells (Fig. [2D](#Fig2){ref-type="fig"}), which was comparable to the drop in cell spreading (Fig. [1C,D](#Fig1){ref-type="fig"}).Figure 2Influence of MMP inhibition on focal adhesion and cell motility of MCF-7, MDA-MB-231 and HT-1080 cells. (**A**) Immunostained images of the focal adhesion protein vinculin (green) and F-actin (red) in untreated, DMSO treated and GM treated cells cultured on stiff PA gels. Scale bar = 20 μm. (**B**,**C**,**D**) Quantitative analysis of size, number of focal adhesion and focal adhesion area per cell in untreated, DMSO treated and GM treated cells (*n* = 2, at least 30--35 cells per condition; \*\*p \< 0.01, \*p \< 0.05, **ns**: not significant). Statistical significance was determined by one-way ANOVA/Fisher test. Error bars represent standard error of mean (±SEM). (**E**) Representative random cell migration trajectories of untreated, DMSO treated and GM treated cells cultured on stiff PA gels. (**F**,**G**) Quantitative analysis of cell speed (*n* = 2, 45--50 cells per condition; \*\*\*p \< 0.001, **ns**: not significant) and directionality ratio (*n* = 2, 35--45 cells per condition; \*\*\*p \< 0.001; \*p \< 0.05; **ns**: not significant) of untreated, DMSO treated and GM treated cells cultured on stiff PA gels. Statistical significance was determined by one-way ANOVA/Fisher test. Error bars represent standard error of mean (±SEM). (**H**) Western blot analysis of phosphorylated-focal adhesion kinase (pFAK^Y397^) in untreated, DMSO treated and GM treated cells cultured on stiff PA gels. β-tubulin served as a loading control (*n* = 2).
Next, to determine if GM induced loss of focal adhesions led to motility defects, random cell motility experiments were performed on stiff gels with untreated, DMSO treated, and GM treated cells. For these experiments, untreated, DMSO treated and GM treated cells were allowed to spread for 8 hrs, and then cell motility experiments were performed for 3 hrs (Supp. Videos [V1](#MOESM2){ref-type="media"}--[V6](#MOESM7){ref-type="media"}). As seen from the representative cell trajectories, GM treatment had negligible effect on the motility of MCF7 cells (Fig. [2E](#Fig2){ref-type="fig"}). However, in both MDAMB and HT cells, the lengths of the traces of GM treated cells were significantly smaller than those of untreated cells (Fig. [2E](#Fig2){ref-type="fig"}); quantification of cell trajectories revealed significant suppression in cell speed (Fig. [2F](#Fig2){ref-type="fig"}) and directionality ratio (Fig. [2G](#Fig2){ref-type="fig"}) in GM treated invasive cells.
Next, to probe the importance of MMP activity is mediating 3D cell invasion, we performed 3D invasion assay by using collagen 3D gels (Supp. Figure [3](#MOESM1){ref-type="media"}). Specifically, cells were encapsulated in 1 mg/ml collagen gels with average pore area of \~4 μm^2^ (Supp. Figure [3A,B](#MOESM1){ref-type="media"}). Since nuclear translocation is rate limiting for migration under confinement^[@CR25]^, and the pore size of these gels (\~2--4 μm in diameter, obtained by approximating the pore as a circle) was smaller than nuclear width of all the three cell types (Supp. Figure [3C,D](#MOESM1){ref-type="media"}), this gel concentration was enough to inhibit cell migration by providing steric hindrance. Cell invasiveness was measured by tracking motility of untreated, DMSO treated and GM treated cells for 12 hrs duration. Similar to our 2D results, both MDAMB and HT cells exhibited faster motility than MCF7 cells in 3D collagen gels, with GM treatment inhibiting cell motility and persistence of MDAMB and HT cells (Supp. Figure [3E--G](#MOESM1){ref-type="media"}). Our results are consistent with findings by others groups who have shown that MMP mediated ECM degradation is critical for 3D invasion through matrices with sub-nuclear sized pores^[@CR26]--[@CR28]^.
The combination of loss of focal adhesions, reduction in motility in 2D, and reduction in invasion in 3D induced by GM treatment suggests that MMP activity is critical for cell spreading, migration and invasion. To probe if these alterations can be correlated with alterations in the phosphorylation levels of focal adhesion kinase (FAK)---a key signaling molecule involved in cell adhesion and migration^[@CR29]--[@CR31]^, levels of phosphorylated FAK (pFAK^Y397^) were assessed in MDAMB, HT and MCF7 cells. Densitometric analysis of immunoblots revealed a significant drop in the expression level of pFAK^Y397^ in GM treated MDAMB and HT cells, but not in MCF7 cells (Fig. [2H](#Fig2){ref-type="fig"}).
Collectively, these results indicate that MMP activity regulates spreading and motility of MDAMB and HT cells on stiff gels at least in part via formation of focal adhesions and FAK^Y397^ phosphorylation.
Inhibition of MMP activity suppresses cell-ECM tractions and induces cell softening in invasive cancer cells {#Sec17}
------------------------------------------------------------------------------------------------------------
Thus far, our results suggest that in highly invasive MDAMB and HT cells, MMP inhibition induces loss of focal adhesions and downregulates pFAK^Y397^. Next to probe the impact of this perturbation on cytoskeletal organization, we used traction force microscopy (TFM) (Fig. [3A](#Fig3){ref-type="fig"}) and AFM to measure cell generated tractions and cell cortical stiffness, respectively. Strikingly, GM treatment was found to inhibit cell-ECM tractions significantly in MDAMB and HT cells, but not in MCF7 cells (Fig. [3B,C](#Fig3){ref-type="fig"}). In addition, analysis of cortical stiffness of cells by AFM revealed significant cortical softening in both MDAMB and HT cells, but not in MCF7 cells (Fig. [3C,D](#Fig3){ref-type="fig"}). Taken together, these results indicate that inhibition of MMP activity in invasive cancer cells perturbs cell mechanical properties via reduction in cell-ECM traction and by inducing cell cortical softening.Figure 3Influence of MMP inhibition on cell-ECM tractions and cortical stiffness of MCF-7, MDA-MB-231 and HT-1080 cells. (**A**) Schematic of traction force microscopy (TFM). Forces exerted by the cells are calculated based on deformations of beads embedded in the gel. The 'constrained' condition corresponds to the case when the cell is attached to the substrate and exerting tractions. The 'unconstrained' condition corresponds to the case when the cell is removed and the beads relax to their original positions. (**B**) Representative traction force maps of DMSO and GM treated cells grown on stiff PA gels (Scale bar = 20 µm). (**C**) Quantitative analysis of root mean square traction (RMS traction) of DMSO treated and GM6001 treated cells grown on stiff PA gels (*n* = 3, 35--45 cells per condition). Stars denote statistical significance (\*\*\*p \< 0.001, ns: not significant). Statistical significance was determined by one-way ANOVA/Fisher test. Error bars represent standard error of mean (±SEM). (**D**) Representative force-indentation curves of DMSO treated and GM treated cells. First 500 nm of the force curves were fit with Hertz equation to obtain estimates of cortical stiffness. (**E**) Quantitative analysis of cell cortical stiffness of DMSO treated and GM treated cells (*n* = 3--4, 100--140 cells per condition; \*\*\*p \< 0.001, \*p \< 0.05). Statistical significance was determined by Mann-Whitney test. Error bars represent standard error of mean (±SEM).
Inhibition of MMP activity perturbs integrin β1 levels and its membrane localization {#Sec18}
------------------------------------------------------------------------------------
Since MMPs are known to bind to integrins^[@CR32]^, and their association is crucial for various cellular processes including cell migration^[@CR33]^, we hypothesized that inhibition of MMP activity perturbs integrins levels and/or its localization at the membrane thereby influencing cell spreading and motility. Indeed, inhibition of integrins by soluble RGD peptide^[@CR34]--[@CR36]^ led to reduction in cell spreading across all the three cell types, and also induced cell softening (Supp. Figure [4A--C](#MOESM1){ref-type="media"}). To probe if cell rounding observed by GM treatment can be attributed to perturbed expression and/or localization of integrin β1, levels of integrin β1were compared between DMSO treated and GM treated cells. Western blots of cell lysates collected from DMSO treated and GM treated samples revealed suppression of integrin β1 in all the cells, with maximal drop in HT cells and minimal drop in MCF7 cells (Fig. [4A](#Fig4){ref-type="fig"}). To see if integrin localization was also perturbed by GM treatment, cells were immunostained with an integrin β1 antibody that binds to the extracellular domain and 3D imaging was performed to determine the membrane localization of integrin β1. Confocal imaging revealed suppression of integrin β1 localization at the basal cell-ECM contact surface in GM treated MDAMB and HT cells (Fig. [4B](#Fig4){ref-type="fig"}). This was also quantitatively confirmed by comparing the mean fluorescence intensity in the region of interest (ROI) (i.e., basal surface) shown in the zoomed-in inset images (Fig. [4B](#Fig4){ref-type="fig"} inset). Tracking the mean intensity automatically corrected for differences in the extent of cell spreading between DMSO treated and GM treated conditions. Plotting of the mean normalized intensity, i.e., mean intensity normalized with respect to the DMSO treated condition, revealed \~20--40% drop in integrin membrane localization in GM treated cells (Fig. [4C](#Fig4){ref-type="fig"}).Figure 4Influence of MMP inhibition on integrin expression levels and its membrane localization in MCF-7, MDA-MB-231 and HT-1080 cells. (**A**) Western blot analysis of integrin β1 in DMSO treated and GM treated cells cultured on stiff PA gels. β-actin served as a loading control (*n* = 2). (**B**) Representative maximum intensity projection images (along the height of the cells (YZ plane)) of DMSO treated and GM treated cells stained for integrin β1 (red) and DNA binding dye DAPI (blue) (Scale bar = 8 µm). Insets show localization of integrin β1 at the basal cell-ECM interface (ROI, region of interest). (**C**) Quantification of mean integrin β1 intensity at the basal surface in DMSO treated and GM treated cells (normalized with respect to mean intensity of DMSO treated cells) (*n* = 2, 25 cells per condition, \*\*\*p \< 0.001, \*p \< 0.05). Statistical significance was determined by one-way ANOVA/Fisher test. Error bars represent standard error of mean (±SEM). (**D**) Quantification of membrane-localized integrins using Atomic Force Microscopy (AFM). Schematic shows probing of cells using 0.1 mg/ml RGD-functionalized spherical probes of diameter 4.5 µm. For this experiment, after indentation, tip was held in position for 10 secs (i.e., dwell time = 10 secs) to allow formation of integrin-RGD bonds, and then retracted. Representative force curve showing indentation of cell and breakage of integrin-RGD bonds during retraction. Maximum adhesive force corresponds to the maximum number of bonds formed. (**E**) Representative retraction curves in DMSO treated and GM treated cells cultured on stiff PA gels. (**F**) Histogram of maximum adhesive force in DMSO treated and GM treated cells cultured on stiff PA gels (*n* = 3--4, 100 cells per condition).
To functionally probe the effect of drop in integrin levels and its altered localization at the cell membrane, an adhesion assay was performed wherein a RGD functionalized spherical AFM tip was brought in contact with a cell, adhesive bonds were allowed to form for 10 secs, after which the tip was retracted (Fig. [4D](#Fig4){ref-type="fig"}). The maximum adhesive force, i.e., the peak force observed during retraction, is indicative of the maximum number of bonds formed (Fig. [4D](#Fig4){ref-type="fig"}), and provides a way of quantifying the extent of GM-induced loss of integrin activity near cell membrane. Tracking of the maximum adhesive force thus allowed us to estimate the extent of integrin activity in DMSO treated and GM treated cells. In DMSO treated cells, maximum adhesive forces observed in MDAMB and HT cells were upto 2-fold higher than those observed in MCF7 cells (Fig. [4E,F](#Fig4){ref-type="fig"}). While no significant differences in the maximum adhesive force was observed between untreated and GM treated MCF7 cells, GM treatment led to significant decrease in the maximum adhesive force in both MDAMB and HT cells, with maximum effect observed in MDAMB cells (Fig. [4E,F](#Fig4){ref-type="fig"}). Together, these results suggest that GM induced defects in cell spreading and motility in highly invasive cells is associated with loss of integrin levels and its localization at the plasma membrane.
MMP proteolytic activity enables mechanoadaptation via integrins {#Sec19}
----------------------------------------------------------------
While our results clearly demonstrate that GM treatment leads to alterations in focal adhesions and cell biophysical properties, it remains unclear if the effects are purely a consequence of extracellular protease activity or can be attributed to other functions of MMPs. To address this question, conditioned media (CM) collected from cells cultured on stiff gels for 48 hrs was added onto fresh Col I coated stiff gels and incubated at 37 °C under sterile conditions (Fig. [5A](#Fig5){ref-type="fig"}). After 48 hrs, the CM was washed out and fresh cells were seeded onto the pre-conditioned surfaces for 12--15 hrs in the presence of DMSO/GM/RGD. While GM treated cells spread to the same extent as that of DMSO treated cells, RGD treatment induced cell rounding on the pre-conditioned surfaces (Fig. [5B,C](#Fig5){ref-type="fig"}) similar to RGD induced cell rounding observed on un-conditioned stiff gels (Supp. Figure [S4](#MOESM1){ref-type="media"}). Consistent with similar spreading between DMSO treated and GM treated cells on pre-conditioned surfaces, integrin expression was nearly identical in DMSO treated and GM treated cells (Fig. [5D](#Fig5){ref-type="fig"}). Furthermore, basal localization of integrin β1 remained unchanged in both MDAMB and HT cells across the two conditions (Fig. [5E,F](#Fig5){ref-type="fig"}).Figure 5Rescue of invasive phenotype of MDA-MB-231 and HT-1080 cancer cells on MMP pre-conditioned surfaces. (**A**) Schematic of generating pre-conditioned surfaces. Conditioned media (CM) was collected from MDA-MB-231 and HT-1080 cancer cells cultured for 48 hrs on Col I coated stiff gels. Fresh Col I coated stiff gels were then incubated with the collected CM for 48 hrs at 37 °C. Subsequently, the gels were washed and a fresh batch of MDA-MB-231 and HT-1080 cells were cultured in the presence of DMSO/GM/RGD for 12--15 hrs. (**B**) Representative fluorescent images of DMSO treated, GM treated and RGD treated cells on pre-conditioned surfaces (Scale bar = 50 µm). Cells were stained for F-actin (green) and DAPI (blue) respectively. (**C**) Quantitative analysis of spreading of DMSO treated, GM treated cells and RGD treated cells (along with RGD peptide, equivalent amount of DMSO was also added) on MMP-pre-conditioned surfaces (*n* = 2, 150--170 cells per condition; \*\*\*p \< 0.001, **ns**: not significant). Statistical significance was determined by Kruskal-Wallis ANOVA/Mann-Whitney test. Error bars represent standard error of mean (±SEM). **(D**) Western blot analysis of integrin β1 in DMSO treated and GM treated cells cultured on pre-conditioned surfaces. β-actin served as loading control (*n* = 2). (**E**) Representative maximum intensity projection of DMSO treated and GM treated cells (along the height of the cells (YZ plane)) cultured on pre-conditioned surfaces and stained for integrin β1 (red) and DNA binding dye DAPI (blue) (Scale bar = 10 µm). Insets show localization of integrin β1 at the basal cell-ECM interface (ROI, region of interest). (**F**) Quantification of mean integrin β1 intensity at the basal surface in DMSO treated and GM treated cells (normalized with respect to mean intensity of DMSO treated cells) (*n* = 2, 30 cells per condition; **ns**: not significant). Statistical significance was determined by one-way ANOVA/Fisher test. Error bars represent standard error of mean (±SEM). (**G**) Western blot analysis of integrin β3 in DMSO treated and GM treated cells cultured on Col I/pre-conditioned surfaces. β-actin served as loading control (*n* = 2). (**H**) Representative maximum intensity projection of DMSO treated and GM treated cells cultured on Col I/pre-conditioned surfaces and stained for integrin β3 (red) and DNA binding dye DAPI (blue) (Scale bar = 5 µm). Insets show localization of integrin β3 at the basal cell-ECM interface (ROI, region of interest). (**I**) Quantification of mean integrin β3 intensity at the basal surface in DMSO treated and GM treated cells (normalized with respect to mean intensity of DMSO treated cells cultured on Col I coated gels) (*n* = 2, 25--30 cells per condition; \*\*\*p \< 0.001; **ns**: not significant). Statistical significance was determined by two-way ANOVA. Error bars represent standard error of mean (±SEM). (**J**) Quantitative analysis of cell cortical stiffness of DMSO treated and GM treated cells on pre-conditioned substrates (*n* = 2, 110--130 cells per condition; **ns**: not significant). Statistical significance was determined by Mann-Whitney test. Error bars represent standard error of mean (±SEM).
To further probe the mechanism by which MMP proteolytic activity influences cell adhesion and spreading, we hypothesized that ECM degradation exposes hidden RGD like motifs of collagen type I thereby allowing other integrin sub-types to engage^[@CR37],[@CR38]^. Since integrin β3 can bind to RGD^[@CR39]^, we probed expression levels of integrin β3 in DMSO and GM treated MDAMB and HT cells cultured on Col I-coated stiff gels as well as on pre-conditioned surfaces. While integrin β3 expression was found to be significantly lower in GM treated cells compared to DMSO controls on Col I-coated surfaces, robust spreading of GM treated cells on pre-conditioned surfaces was associated with more than 2-fold integrin β3 expression compared to that on Col I-coated gels (Fig. [5G](#Fig5){ref-type="fig"}). In line with higher integrin β3 expression observed on pre-conditioned surfaces, immunostaining revealed increased integrin β3 localization at the cell-ECM interface in both DMSO treated and GM treated cells on the pre-conditioned surfaces compared to that on Col I-coated surfaces (Fig. [5H,I](#Fig5){ref-type="fig"}).
In line with normal cell spreading and robust F-actin staining observed in GM treated cells on the pre-conditioned surfaces, probing of cell mechanical properties revealed no differences in cortical stiffness of DMSO treated and GM treated cells (Fig. [5H](#Fig5){ref-type="fig"}). Collectively, our results suggest that MMP mediated pre-conditioning of collagen type I enables cell mechanoadaptation via integrins.
Discussion {#Sec20}
==========
In this work, we have demonstrated the role of MMPs in regulating stiffness-dependent responses in invasive cancer cells. Our results reveal that stiffer substrates enhance MMP activity. Interestingly, inhibition of MMP activity induces cell rounding through loss of focal adhesions, suppresses traction generation, cell motility and cell invasiveness, and softens cells. These phenotypic defects could be rescued if cells were seeded on MMP pre-conditioned surfaces. Overall, our results suggest that ECM stiffening-induced up-regulation of MMP extracellular proteolytic activity contributes to maintenance of invasive phenotype in MDAMB and HT cancer cells.
Epithelial cancers are associated with ECM stiffening^[@CR40]^. Such stiffening, achieved by increased deposition and crosslinking of fibrillar ECM proteins including collagen, leads to reduction in pore size^[@CR21],[@CR41]^. This should ideally limit cancer invasiveness by providing increased steric hindrance; instead, cells become more invasive^[@CR5],[@CR22],[@CR42]^. Together, our 2D cell motility and 3D invasion experiments suggest that increased invasiveness is a consequence of increased MMP activity in invasive MDAMB and HT cells. The absence of stiffness-dependent changes in MMP activity observed in non-metastatic MCF7 cells suggests that stiffness-dependent modulation of MMP activity is a property of highly invasive cancer cells. Our results further suggest that MMP activity mediates stiffness adaptation by modulating integrins, with inhibition of MMP activity suppressing mechanosensing leading to defective cell spreading and motility.
Previous studies have shown that extracellular activity of MMPs generates cleaved fragments of ECM components^[@CR43]^, which serve as chemotactic cues and stimulate directed migration of fibroblasts^[@CR44]^ and keratinocytes during wound healing and tissue repair processes^[@CR45]^. In addition, MMP mediated cleavage of laminin-5 and collagen IV have also been shown to expose cryptic binding sites which aid in cell migration^[@CR46],[@CR47]^. MMP 1 mediated collagen I degradation is also crucial for epithelial cell migration during wound closure^[@CR48]^. GM-induced loss of cell spreading and motility defects may be attributed to the absence of cleaved ECM fragments and/or exposure of cryptic domains, as cell spreading is rescued on MMP pre-conditioned matrices even in the presence of GM. Consistent with this, we observe increase in integrin β3 localization in MDAMB and HT cells at the basal cell surface on MMP pre-conditioned surfaces.
Several reports have documented regulation of outside-in signaling by MMPs. For example, Weiss and co-workers have shown that catalytic activity of MT1-MMP regulates skeletal stem cell fate via integrin β1 signaling^[@CR10]^. Another group has shown that MMP 1 activity at the cell surface of platelets can induce thrombosis via PAR1 (protease activated receptor) signaling^[@CR49]^. MMP substrate specificity is not just limited to ECM components, but also includes growth factors such as TGF-β^[@CR50]^, which is known to play a significant role in cancer progression^[@CR51]^. Studies suggest that MMP 9 and MMP 2 can proteolytically activate TGF-β at the cell periphery and induce angiogenesis and tumor invasion^[@CR52]^. In our study, MMP inhibition-induced downregulation of pFAK^Y397^, suppression of cell-ECM tractions, softening of cell cortex and loss of integrins at the cell surface in invasive MDAMB and HT cancer cells illustrates the importance of MMP activity in regulating localization of cell surface receptors and its downstream signaling processes. However, the exact mechanism of modulation of integrin stability by MMP activity remains unknown. Recent studies have shown that co-localization and interaction between MT1-MMP and integrin β1 is essential for mammary morphogenesis, with perturbation of either one of the two suppressing morphogenesis^[@CR11]^. In addition, both MMP 2 and MMP 9 have also been shown to interact with integrins^[@CR53]^. Therefore, GM-induced alterations in cell phenotype are probably brought about by alterations in the interaction between integrins and MMPs.
Recent studies in fibroblasts have established a mechanistic link between MT1-MMP mediated extracellular proteolysis and cytoskeletal and nuclear organization^[@CR12]^. Similarly, in skeletal stem cells, ECM remodeling has been shown to regulate RhoGTPase signaling and pericellular rigidity^[@CR10]^. Previously, Sheetz and co-workers have demonstrated the role of integrin β1 in determining adhesion strength and integrin β3 in regulating mechanotransduction^[@CR54]^. In our study, cell rounding on stiff surfaces in the presence of GM and phenotypic rescue of MDAMB and HT cells on MMP pre-conditioned surfaces even in the presence of GM suggests that MMP pre-conditioning exposes hidden RGD-like motifs in collagen^[@CR37],[@CR55]--[@CR57]^. Subsequently, exposure of these RGD-like motifs induce expression of other integrin sub-types (integrin β3 in our case)^[@CR39]^ thereby regulating mechanoadaptation on stiff collagen coated surfaces. Overall, our results thus illustrate the existence of a crosstalk between MMP mediated ECM remodeling and cell mechanical properties mediated via integrins.
In summary, our results demonstrate ECM stiffness-dependent modulation of MMP activity in invasive cancer cells, and the role of this increased MMP activity in sustaining the invasive phenotype of cancer cells through modulation of integrins. Future studies will specifically focus on understanding the contributions of distinct soluble and membrane bound MMPs in regulating cell biophysical properties.
Electronic supplementary material
=================================
{#Sec21}
Supplementary information MDA-MB-231 Untreated MDA-MB-231 DMSO MDA-MB-231 GM6001 HT1080 Untreated HT-1080 DMSO HT-1080 GM6001
**Electronic supplementary material**
**Supplementary information** accompanies this paper at 10.1038/s41598-017-14340-w.
**Publisher\'s note:** Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Authors acknowledge financial support from Department of Biotechnology (Govt. of India) (Grant \# BT/PR12705/BRB/10/1361/2014). AD was supported by fellowships from Department of Biotechnology (Govt. of India). Authors would also like to thank IIT Bombay-IRCC for providing Bio-AFM, Confocal Microscopy and Cryo FEG-SEM facilities.
A.D. performed most of the experiments and analysed the data. M.M. performed all the western blot experiments. A.B performed all the microscopy and assisted in acquiring 2D motility movies. S.K. assisted in writing Matlab codes for AFM data analysis and Traction force data analysis. A.D. and S.S. designed the experiments and wrote the manuscript.
Competing Interests {#FPar1}
===================
The authors declare that they have no competing interests.
| 2024-02-14T01:26:28.774034 | https://example.com/article/2244 |
LIVING AND LEARNING PROGRAMS
Breadcrumb
ARHU’s living and learning programs attract a diversity of highly talented undergraduates with shared interests to live in the same residence hall, take courses together and cultivate relationships with faculty mentors. Many of the living-learning seminars support graduation requirements and utilize faculty from across the college and campus to enrich the student experience.
Curricula vary by program, but all include specialized seminars, extensive co-curricular programming, collaborative research-centered presentations and performances, community outreach such as student-run mentoring and teaching programs, and research practica. | 2024-07-03T01:26:28.774034 | https://example.com/article/3423 |
Q:
Product of two sums over the same interval
I have some terms of an expression as sums but I would like to simplify the solution to an easier and less complicated one. What I have is $$ X = \sum_{k=0}^\infty \left(\frac{z}{5}\right)^k \sum_{r=0}^\infty \left(\frac{2z}{5}\right)^r$$ Can this be reduced to a single sum (It should be an infinite sum and not just an expression)? Any help is greatly appreciated. Thanks.
A:
First of all, you should be aware of the radius of convergence for the sum (the sum is convergent for $|z|<\frac{5}{2}$). Another thing to point out is that it's wise to use different indices for those two sums to avoid confusion (e.g. sum over $k$ and $j$).
That being said, you may write the product as $$ X = \sum_{k=0}^\infty \left(\frac{z}{5}\right)^k \sum_{j=0}^\infty \left(\frac{2z}{5}\right)^j$$ and proceed with the formula for the sum of the infinite geometric series $$\sum_{k=0}^\infty aq^k=\frac{a}{1-q},$$ as the answer by Aniket elaborates.
If you want to reduce it to a single sum, you may take the finished expression and expand it into an infinite sum (Taylor/McLaurin/Laurent series, depending on what you want to achieve).
What you can also do is write down the first expression using the polynomial multiplication formula: $$A=\sum_{k=0}^\infty \alpha_k x^k, \space B=\sum_{j=0}^\infty \beta_j x^j$$ $$\Rightarrow C=AB=\sum_{n=0}^\infty \left(\sum_{k+j=n}\alpha_k \beta_j\right)x^n$$ Note that here you have to choose the same $x$ for sum $A$ and $B$ for the formula to be correct (e.g. $x=\frac{z}{5}$). The coefficients are then $\alpha_k=1$ and $\beta_j=2^j$ so the final expression can be simplified to $$X=\sum_{n=0}^\infty \left(\frac{z}{5}\right)^n \sum_{j=0}^{n}2^j=\sum_{n=0}^\infty\left[ \left(\frac{z}{5}\right)^n\left(2^{n+1}-1\right)\right]$$ You can easily check that this sum yields the same closed form as Aniket's result.
| 2024-03-25T01:26:28.774034 | https://example.com/article/4814 |
DA: Stockton Officer Won’t Be Charged In Fatal 2016 Shooting
STOCKTON (CBS13) – The San Joaquin County District Attorney’s office says the deadly 2016 officer-involved shooting of a Stockton man was justified.
Colby Friday, 30, was shot and killed by Officer David Wells in August 2016.
Officers confused Friday with another suspect and attempted to make contact, but he took off running. Friday was armed and refused to comply, officers said.
The family filed a wrongful death lawsuit one year later against the city, the department and the officer involved.
San Joaquin County District Attorney Tori Verber said in a statement:
“My office does not hesitate to hold law enforcement accountable for criminal behavior when the evidence supports it, but that was not the case in this situation. I have talked with Mr. Friday’s family in the past and am doing so today and my heart breaks for his mother, his loved ones and our entire Stockton community who lost a loving father and son.”
The district attorney’s office says the family of Friday has been notified of the decision and is being given an opportunity to review the findings. | 2024-02-06T01:26:28.774034 | https://example.com/article/8536 |
JACKSONVILLE, Fla. -- Friday, March 1st is the deadline for sequestration. The proposed cuts could impact families and workers of Head Start and Early Head Start programs.
If the cuts go through, Head Start and Early Head Start programs would be eliminated for 2,700 kids in the state of Florida and 1,700 in Georgia. In 2008 in Florida, nearly 41,000 kids were enrolled in those programs.
Kids like Kiyontay Edee. Kiyontay and his mother, Misline, have been going to Episcopal Children's Services since Kiyontay was just seven months old.
"He speaks two languages. They teach him a little bit of the basic Creole and then the basic English. He is learning so much!"
Kiyontay is now almost two years old, and Edee worries what the federal cuts would do to her family.
CEO of Episcopal Children's Services Connie Stophel said the organization has already been working on 80 percent of its budget and sequestration could mean bad news for the programs.
"We would have to cut our programs back to four days a week," Stophel explains. "For us, the longer-term impact is if it goes through and it stays, then we have to really look at the impact on about 65 children who we would have to defund the next year, and terminating about 20 staff members."
Stophel said if the federal cuts happen, the furlough would start immediately through September. Then, October 1st would be when ECS would look at cutting eight percent of its staff and 10 percent of the kids it serves. She said those students would be selected using a point system, which is based on need.
She said it doesn't make the decision any easier,
"We look into these beautiful faces, and I just think 'Are you the one that we won't be able to serve next week?'"
The four-day day week would also be hard on the families of the students, because, like Edee, many parents work during the time their children are at Head Start.
"To have our child be able to come here seven hours a day, it helps us because we're not paying for that childcare, which we can't afford right now," Edee says.
Episcopal Children's Services says it plans to seek outside funding, such as private grants and fundraisers, to help cover the deficit. | 2023-08-12T01:26:28.774034 | https://example.com/article/1523 |
Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab in the trial SAKK 50/07.
The O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical trials with temozolomide plus bevacizumab therapy in metastatic melanoma patients are ongoing, although the predictive value of the MGMT promoter methylation status in this setting remains unclear. We assessed MGMT promoter methylation in formalin-fixed, primary tumor tissue of metastatic melanoma patients treated with first-line temozolomide and bevacizumab from the trial SAKK 50/07 by methylation-specific polymerase chain reaction. In addition, the MGMT expression levels were also analyzed by MGMT immunohistochemistry. Eleven of 42 primary melanomas (26%) revealed a methylated MGMT promoter. Promoter methylation was significantly associated with response rates CR + PR versus SD + PD according to RECIST (response evaluation criteria in solid tumors) (p<0.05) with a trend to prolonged median progression-free survival (8.1 versus 3.4 months, p>0.05). Immunohistochemically different protein expression patterns with heterogeneous and homogeneous nuclear MGMT expression were identified. Negative MGMT expression levels were associated with overall disease stabilization CR+PR+SD versus PD (p=0.05). There was only a poor correlation between MGMT methylation and lack of MGMT expression. A significant proportion of melanomas have a methylated MGMT promoter. The MGMT promoter methylation status may be a promising predictive marker for temozolomide therapy in metastatic melanoma patients. Larger sample sizes may help to validate significant differences in survival type endpoints. | 2024-02-15T01:26:28.774034 | https://example.com/article/2341 |
Discal cysts.
Discal cysts are rare lesions that can result in refractory sciatica. Because they are so rare, their exact origin and details of the clinical manifestations are still unknown. The authors report on five men treated for discal cysts. The mean age of the patients at the time of the surgery was 32 years (range 25-38 years). All patients suffered from lower-extremity pain and the results of the straight leg-raising test were positive in all cases. Three patients reported motor weakness and four had sensory disturbance--symptoms similar to those found in patients with lumbar disc herniation. Magnetic resonance imaging demonstrated spherically shaped extradural lesions of various sizes with low and high signal intensities on T1- and T2-weighted images, respectively. Discography revealed obvious communication between the cyst and the intervertebral disc with reproducible leg pain in all patients. All patients underwent posterior decompression and excision of the cysts either with or without additional discectomy. The radicular symptoms were remarkably improved in all patients immediately after surgery, and no recurrent lesions were noted during follow up. | 2024-01-11T01:26:28.774034 | https://example.com/article/4596 |
Fits aftermarket or OEM Glock Gen 3 G19/23 parts
Reinforced polymer material – black
Undercut trigger and extended beavertail
Picatinny light rail
Magwell flare
Aggressive grip texture
Vertical grip angle
Includes locking block and rear rail module
The Polymer 80 PFC9 Compact Pistol Frame is basically like a stripped lower receiver that you can purchase and assemble with whatever parts that you want to use. It features an enhanced ergonomic grip that is more vertical than other similar striker fired pistols. This P80 frame is made from reinforced black polymer with an aggressive grip texture perfect for gloved use. Additionally, it has a high undercut beneath the trigger allowing you to get a higher purchase for better recoil control and an extended beavertail to prevent slide bite. It features a standard picatinny rail for light compatibility at the expense of holster compatibility and is not guaranteed to fit in some G19 holsters. A slight bevel on the magazine well aids in reloads and is still compatible with the Magpul magwells for an even deeper flare. Build your dream pistol today with the P80 PFC9 Compact Frame.Polymer 80 is known for designing 80% receivers and jigs, so you can build your own Glock style handgun or AR-15 right in your garage. They have grown in popularity so fast that they are now offering their own completion kits with all the internal parts you need to finish a build. Whether you want to build a handgun or rifle, P80 has you covered. | 2024-07-12T01:26:28.774034 | https://example.com/article/8728 |
Holiday Gift – Desired State Configuration (DSC) Resource Kit Wave-1
Continuing with the tradition of holiday gifts to the PowerShell community, the PowerShell team has just released DSC Resource Kit Wave-1 – a set of PowerShell modules that contain DSC resources and example configurations. The various modules that are part of DSC Resource Kit Wave 1 can be found here.
When DSC was introduced in PowerShell v4, we shipped a set of built-in resources. However one of the important features of DSC is the ability to create custom resources in PowerShell. Our previous blog posts detail how to author resources and how to deploy resources. In order to encourage the community to create more DSC resources and help boot strap the authoring process, we are releasing this first wave.
We have introduced a new naming convention for these modules and resources – they contain an “x” in them like xWebAdministration, MSFT_xWebsite, etc. The “x” stands for experimental – which means these resources are provided AS IS and are not supported through any Microsoft support program or service. We will monitor these, take feedback and may provide fixes on a “fix forward” basis – that is to say we may simply republish with fixes in future. I am deliberately using the word “may” to indicate no guarantees of any sort. However, you are free to adapt these to your environment and make changes as necessary.
Description of Resources
To discover all the resources available as part of the resource kit, use the Get-DSCResource cmdlet:
We reserve resource and module names without prefixes (“x” or “c”) for future use (e.g. “MSFT_WebAdministration” or “Website”). If the next version of Windows Server ships with a “Website” resource, we don’t want to break any configurations that use any community modifications. Please keep a prefix such as “c” on all community modifications.
As specified in the license, you may copy or modify this resource as long as they are used on the Windows Platform.
Requirements
The DSC Resource Kit requires Windows 8.1 or Windows Server 2012 R2 with update KB2883200 (aka the GA Update Rollup). You can check whether it is installed by running the following command:
Once the resources are deployed, they can be used in configurations. An example configuration is given below (this example together with the sample website files are available as part of the examples of xWebAdministration module):
Note: Any resource that is not shipped as part of Windows, needs to be available in a module in PSModulePath and must be imported (using Import-DSCResource keyword) before it can be used in a configuration.
Feel free to leave your feedback in the comments section as well as use the Q&A section in the TechNet pages. You can also provide feedback here in the connect page
> The PowerShell provider * does not exist at the PowerShell module path nor is it registered as a WMI provider.
I found something odd with this to do with the Machine level PSModulePath environment variable.
When "C:Program FilesWindowsPowerShellModules" is IN that path, Get-DscResource works & running the configuration script to generate the .mof file works, but running Start-DscConfiguration fails with the above message.
When "C:Program FilesWindowsPowerShellModules" is NOT IN that path, Get-DscResource can't find the resource, and running the configuration script fails, unable to import the module, however if the mof file has previously been generated, Start-DscConfiguration succeeds.
To workaround this, our build script is adding the path to PSModulePath for the first step, and removing it for the second.
We're looking into alternative ways to get the first step to succeed, so we never have to change the Machine level PSModulePath at all – but no luck yet.
Not sure if this quirk can shed any light on the root cause of why us and others are getting this error message.
Effective immediately, we've fixed the missing resource problem in xWebAdministration 1.3.2.4. All missing files/directories should be back in all TechNet zip files and on the Gallery. Sorry for the confusion and the delay.
I copied the example configuration provided to set up a new IIS website. 1st of all, I get a quiugly broken redline on xWebsite, indicating "Undefined DSC resource 'xWebsite'. Use Import-DSCResource to import the resource.
"Import-DscResource -Module xWebAdministration" is declared in the begining of the script, when I run the script I get
"The term 'Import-DscResource is not recognized as the name of a cmdlet………."
I searched this site, followed, what I was able to understand that fix KB2883200 is is "InstalledOn = 3/24/2015", yesterday.
Issuing Get-Dsecresource, I can see clearly 2 modules, "xWebApplication and xWebVirtualDirectory".
Also, I discovered that Import-DscResource is not recognized neither on the commandline nor in the help in ISE
What can be missing? Thanks in advance
3 years ago
Aaron Jensen
So, I, too was getting this error:
> The PowerShell provider * does not exist at the PowerShell module path nor is it registered as a WMI provider.
for one of my moduels on a server that previously was working and downloading stuff. Rebooting didn't work. Killing WMI processes didn't work. It turns out, I had changed a .mof file without updating its checksum. As soon as I updated my checksum, things started working again.
While sorting out why my custom resource was not being recognized I went to apply a configuration that has Import-DscResource within it and I received the following error on a Server 2012 R2 machine when I process the configuration to create the MOF:
PS C:UsersAdministrator> Import-DscResource
Import-DscResource : The term 'Import-DscResource' is not recognized as the name of a cmdlet, function, script file,
or operable program. Check the spelling of the name, or if a path was included, verify that the path is correct and
I have no idea what happened. Unless something was uninstalled while processing an 'absent' of my application.
4 years ago
Peter
I saw the same issue as Mark and gt where I was getting the error message that the PowerShell provider does not exist at the PowerShell module path nor is it registered as a WMI provider when I ran Start-DscConfiguration. In my case, I was using the xHyperV module. I stopped all the WMI processes hosting DSC engines but that did not help.
Interestingly, after I rebooted the system, the error disappeared.
2 years ago
Brandon
A reboot fixed this exact same issue for me too. I was able to generate the MOF file, but unable to apply the configuration using Start-DscConfiguration. Once I added the module path to the PSModulePath environment variable and rebooted, everything worked.
Regarding the above issue, I wanted to confirm that y'all were using: "Import-DscResource -Module MyDscModule" in your configuration. Not including the explicit import can cause the issue that you were describing.
To be clear – you should not have to install custom DSC modules into the system directory.
Just so I’m clear on the details of your problem, I’ll try to restate what you said above:
• When MyDSCModule is in C:Program FilesWindowsPowerShellModules, you can import MyDSCModule using Import-Module.
• When MyDSCModule is in C:Program FilesWindowsPowerShellModules, you can “compile” a configuration using MyDSCModule into a .mof file (e.g. running configuration “MyConfiguration” to generate the MyConfiguration folder)
• However, when you actually try to “apply” the MyConfiguration.mof to localhost, you encounter the above error.
This is an odd problem. Because you can successfully compile the .mof:
• Your problem does not appear to relate to the Update mentioned above (KB2883200).
• Your configuration is probably not malformed in any way (e.g. missing Import-DSCResource –module MyDSCModule)
Because it works when MyDSCModule is in the System Directory:
• The MyDSCModule on the target node should be the same version as the one used to generate the .mof.
Is it possible that you have multiple versions of MyDSCModule deployed to different areas of the module path? Is there any way you can share you configuration with us by uploading it to CodePlex or a similar site?
Thanks,
John Slack
Program Manager
PowerShell Team
4 years ago
Mark Johnson, Esquire
I am having the same issue as "gt". When I put my DSC module in the recommended path of "C:Program FilesWindowsPowerShellModulesMyDscModule", the
Start-DscConfiguration -wait -Verbose -Path "MyConfiguration"
Fails with the message :
"The PowerShell provider MyDscModule does not exist at the PowerShell module path nor is it registered as a WMI provider.
I am able to import the MyDscModule in PowerShell using "Import-Module MyDscModule"
I verified the $env:PSModulePath variable contains the path "C:Program FilesWindowsPowerShellModules" and the value is stored at the "Machine" scope ([environment]::GetEnvironmentVariable("PSModulePath","Machine"))
If I move the module to "C:windowssystem32WindowsPowerShellv1.0ModulesMyDscModule", then the Start-Configuration command works fine.
I did kill the wmi* process as outlined above.
I really do not want to install our custom DSC modules into the system directory.
@gt – You need to have a xComputerManagement.psd1 file under xComputerManagement folder for it to be valid module. Are you missing that?
4 years ago
gt
@powershell team , thanks for the help much appreciated , we tried running the get-process command gps wmi* | ? {$_.modules.ModuleName -like "*DSC*"} on the localhost/target machine where our custom DSC resources reside but it returns nothing.
Quick question unzipping one of the examples into <$env:psmodulepath> C:Program FilesWindowsPowerShellModulesxComputerManagement
get-dscresource shows for this resource
Name Module
xComputer xComputerManagement
we generate a localhost.mof file ok and it contains ModuleName = "xComputerManagement";
we run the command start-dscconfiguration -wait -verbose -path c:dsconfiguration
The PowerShell provider xComputerManagement does not exist at the PowerShell module path nor is it registered as a WMI
provider.
what do we need to do for it to locate the module as there is no xComputerManagement.psm1 file in the parent directory , how do we tell the DSC engine to look in .DSResourcesMSFT_xComputerMSFT_xComputer.psm1 where the logic is for get/set/test
@gt – Did you updated the resources on the target machine as well? You might have to stop the WMI process on target machine that is hosting DSC engine for updates to be reloaded. You can find it using the following expression | 2024-03-05T01:26:28.774034 | https://example.com/article/5994 |
A 32-year-old Mattel Intellivision Game by INTV
Emulated in MAME !
DESCRIPTION
Guide your knight through the deadly mazes of Thunder Castle, slaying evil dragons, sorcerers and demons as you go. Watch for gates that block your path... magic objects that grant special powers, extra points, or extra lives...and magic creatures that energize your knight. Complete all three mazes -- forest, castle and dungeon -- and the game starts over at a faster speed. Continue playing, increasing your score, until all of your knight's lives are lost.
OBJECT OF THE GAME: To score the highest number of points by slaying the evil guardians of each maze and collecting magic objects. The player with the highest score at the end of the game is the winner.
TECHNICAL INFORMATION
Model 4469
TRIVIA
On January 22, 1982, Vice President of Application Software Gabriel Baum announced a competition for the best game idea with a magic theme. The reason was never announced -- probably Marketing had an idea for a promotional tie-in somewhere -- but whatever it was must have fallen through, since Gabriel didn't bother picking a winner until April.
The winner was Connie Goldman. Connie had been hired as a programmer, but it quickly became apparent that her strength was character animation. She started work on the game, originally titled Magic Castle, but she was continuously pulled away from it to do graphics for other, higher priority games and to put together demos for Marketing. (She did excellent animations of Peanuts, Garfield and McDonalds characters, among others, when Marketing was trying [unsuccessfully] to obtain those licenses.)
Whenever she had time she would return to her game, which had begun appearing in Mattel Electronic catalogs as Mystic Castle, but it was further delayed when Bill Goodrich got permission to use half of the animated characters from it in his own, higher priority, Intellivoice game Quest.
After completing his own game, Mind Strike, and overseeing the programming of Bump 'n' Jump, David Warhol was given the task of helping Connie finish Mystic Castle. They strengthened the game play and, after the cancellation of the voice games, reinstated the animations stolen for Quest. Under the new name Thunder Castle, the game was completed, well over a year after Connie had first started working on it.
Mattel Electronics was closed shortly thereafter, before the game went into production; Thunder Castle was finally released by INTV Corporation in 1986.
TIPS AND TRICKS
* Lure an evil guardian as close as possible to your knight before touching a magic creature. Your knight will be energized for only a few seconds and meanwhile, the guardian is running away from you!
* Try to anticipate gates, to trap an evil guardian in a dead end. Corners also slow guardians down.
* Pick up the most useful magic objects. Although all objects give points, some are more useful than others. Exceptions: Always pick up coins and candlesticks. The extra points and lives don't affect other magic powers.
* Avoid touching the comb whenever possible, but don't be afraid to sacrifice points, if the comb stands between your knight and a safe retreat.
* Easter Egg: Press 0 (zero) on either hand controller while the title screen is displayed to see game credits. | 2023-09-08T01:26:28.774034 | https://example.com/article/8658 |
Dies, such as focal plane arrays, are typically produced collectively in arrays on wafer substrates. Back-end or back-end of line fabrication of focal plane arrays is often performed serially after front-end wafer-level detector processing. Entire wafers are generally front-end processed and singulated, and then back-end processing is performed at a die-level. Back-end processing can include processes such as thinning, polishing, coating, and hybridizing. Typically, thinning, polishing, coating, and hybridizing processes are performed after singulating the wafer into individual dies. Thus, if there are ten arrays on a wafer, the thinning process is performed ten different times, resulting in a time-consuming and expensive processing technique. As a result, a significant portion of focal plane array cost is attributed to the traditional approach of back-end of line fabrication. The traditional approach of wafer-level processing without a carrier has been tried, but has been typically abandoned because of damage that occurs to the backside optical surface during backside processing.
As a result, there is a need for improved techniques for fabricating focal plane arrays for imaging devices such as Group III-V and II-IV compound semiconductors for infrared cameras. | 2023-09-09T01:26:28.774034 | https://example.com/article/7520 |
Note: If things are not working as described below check the version information for parallel.
parallel --version
WARNING: YOU ARE USING --tollef. IF THINGS ARE ACTING WEIRD USE --gnu.
...
Either add --gnu to all your parallel commands, or edit /etc/parallel/config and make sure it lists --gnu and not --tollef.
Most Linux utilities are single threaded, and when dealing with really large files a single core can be a severe bottleneck. One way to work around this limitation is the GNU parallel command, which I'm still playing around with and finding uses for -- but looks like a promising way to speed up a lot of things I do on a daily basis.
A common time sink with big computers is big logs, and waiting forever to grep them.
Let's break down the command a bit. We cat the contents of the file to the parallel command, which we give the --pipe option which splits STDIN to multiple copies of the command we supplied. (--pipe is the same as --spreadstdin, which is more readable but longer)
But you'll notice is actually took longer, and it chewed up a lot more CPU. What's going on here? By default parallel splits the input into 1 megabyte blocks and hands each to a single instance of the command, with the number of simultaneous instances set to the number of cores by default. Launching grep 102 times to grep 1 meg is pretty wasteful. Let's tune things a little bit:
Another common command to throw large files at is awk. However, depending on what you’re trying to accomplish splitting the input may prevent you from accomplishing certain tasks — like adding all the values of a field. To work around this you can rewrite your commands to perform the same task in two steps. The first step to process blocks of the input, the second step to combine the results.
The caveat being that because it is parallel-izing these commands sometimes the results aren't as reproducible as they would inherently be on a single core. You've got to be really careful with the options to parallel, and the assumptions you make when assembling your commands. When in doubt use the -k (--keep-order) to return the output in the same order as the input, as opposed to as soon as the command running on a particular block of input finishes.
In the above command set delimiter is set to spaces to split between each of the input numbers, in the first one output order is maintained (-k), and limited to 4 cores (-j4). The input numbers are inserted in place of the {} in the sleep\; echo {} command.
By maintaining output order parallel can be used to bzip2 files as well: | 2023-09-29T01:26:28.774034 | https://example.com/article/5670 |
President Donald Trump asked Commerce Secretary Wilbur Ross during a Wednesday meeting to consider investigating automobile, truck, and parts imports on the basis of national security, a decision that could lead to tariffs on such imports.
The President issued a statement on that meeting on Wednesday evening:
Today, I met with Secretary of Commerce Wilbur Ross to discuss the current state of our automobile industry. I instructed Secretary Ross to consider initiating a Section 232 investigation into imports of automobiles, including trucks, and automotive parts to determine their effects on America’s national security. Core industries such as automobiles and automotive parts are critical to our strength as a Nation.
Trump forecast a coming announcement on autos when he tweeted on Wednesday morning:
There will be big news coming soon for our great American Autoworkers. After many decades of losing your jobs to other countries, you have waited long enough! — Donald J. Trump (@realDonaldTrump) May 23, 2018
After meetings between China and U.S. trade representatives over the past weeks in Beijing and Washington, DC, China announced its intention to cut tariffs on U.S. auto exports to China.
The United States has relented in potential tariffs on Chinese imports of $150 billion following the bilateral U.S.-China trade meetings. As for U.S. section 232 tariffs on steel and aluminum from all countries except those specifically exempted, those will remain, according to Treasury Secretary Steve Mnuchin.
Secretary Ross unexpectedly canceled a Wednesday morning speaking engagement at the Heritage Foundation, according to Breitbart News reporter John Carney.
In early March, the White House released a fact sheet on section 232 investigations and tariffs. It began with the explanation, “Section 232 investigations help to determine the effects of imports on America’s national security and give the President the ability to address any threats to national security by restricting imports through tariffs.”
The Department of Commerce has 270 days from initiation of the investigation to issue a report to the President with findings of the investigation.
***Update***
Following his discussion with the President, Sec. Ross decided to open a section 232 investigation into the national security threat posed by imports of automobiles and automotive parts. Ross has informed Secretary of Defense James Mattis of the investigation.
“There is evidence suggesting that, for decades, imports from abroad have eroded our domestic auto industry,” said Secretary Ross. “The Department of Commerce will conduct a thorough, fair, and transparent investigation into whether such imports are weakening our internal economy and may impair the national security.”
A Commerce department release offered as background for the decision two decades of growth in the share of imported passenger automobiles over domestically produced autos.
The release detailed the focus of the investigation:
This investigation will consider whether the decline of domestic automobile and automotive parts production threatens to weaken the internal economy of the United States, including by potentially reducing research, development, and jobs for skilled workers in connected vehicle systems, autonomous vehicles, fuel cells, electric motors and storage, advanced manufacturing processes, and other cutting-edge technologies
A hearing date will be set and announced shortly in the Federal Register with an invitation for industry and the public comment to assist in the investigation.
Follow Michelle Moons on Twitter @MichelleDiana | 2023-08-21T01:26:28.774034 | https://example.com/article/9025 |
Dorababu Pendem
Dorababu Pendem is an Indian politician and member of the YSR Congress Party. He was a member of the Andhra Pradesh Legislative Assembly from the Pithapuram constituency in East Godavari district on Bharatiya Janata Party ticket from 2004 to 2009. He joined YSR Congress Party in 2012 and contested in 2014 Andhra Pradesh Assembly elections from Pithapuram constituency and lost. Notably he is one of the close associates of Late Mr.Y.S.Rajasekhar Reddy.
References
Category:People from East Godavari district
Category:YSR Congress politicians
Category:Bharatiya Janata Party politicians from Andhra Pradesh
Category:Members of the Andhra Pradesh Legislative Assembly
Category:Living people
Category:Telugu politicians
Category:21st-century Indian politicians
Category:Year of birth missing (living people) | 2024-07-01T01:26:28.774034 | https://example.com/article/2770 |
the offer
If you're starting to look a little frizzy around the edges, smooth things over with a visit to Head Spa by John Azzi on Market Street
Keratin smoothing treatment with masque and blow dry for one person is $99 (valued up to $500)
Keratin smoothing treatment with masque and blow dry for two people is $189 (valued up to $1,000)
The L'Abrea Keratin treatment is Australian-made and also 100% vegan!
Designed to leave you with silky smooth locks, with results lasting for up to three months
Your locks will also be treated to a deep repair masque, plus a professional blow dry
Available Monday to Saturday at the CBD salon (Sundays by appointment only)
more info
If there's one thing you can count on to make a bad hair day better, it's an award-winning hair stylist like John Azzi.With 30 years of experience making hair look heavenly, this maestro has opened Head Spa by John Azzi in the city centre, a salon staffed by a team of experienced and passionate stylists.
Book yourself in for a frizz-fighting Keratin treatment and look forward to leaving with smooth locks that are sure to turn heads. A deep repair masque is also included to restore the hair's natural shine and lustre for a photo-ready result.
The Fine Print
Available Monday to Wednesday 8:30am-5:30pm; Thursday 8:30am-8:30pm; Friday and Saturday 10:00am-7:00pm. Available on Sundays by appointment only. Not valid on public holidays
Entire voucher value must be used in one visit
Members can purchase one voucher for themselves and one voucher as a gift for a different recipient
Maximum one voucher per person/booking
Please note: Voucher is valid for short-medium length hair. A surcharge from $20 applies for long hair (past the shoulder), and a higher surcharge may apply for extra thick or extra long hair. If unsure, please contact Head Spa by John Azzi directly before purchasing the deal
Please be advised that on some types of hair the use of keratin treatments may lighten or slightly change your hair colour
Products cannot be used by pregnant or nursing women
Not suitable for afro hair. Results may vary depending on hair type and quality and are not guaranteed. Refunds are not available in the event that the treatment is not able to successfully treat your hair
Results may vary. Images are for illustration purposes only and may not reflect the actual offer
Company
Additional Info
Business Owners
LivingSocial supports the Responsible Service of Alcohol. WARNING: Under the Liquor Control Reform Act 1998 it is an offence: To supply alcohol to a person under the age of 18 years (Penalty exceeds $6,000); For a person under the age of 18 years to purchase or receive liquor (Penalty exceeds $500). Lux Group Ltd Liquor Licence No. 36123474. | 2023-08-19T01:26:28.774034 | https://example.com/article/6103 |
Ainge is a clown. McHale handed him a "5-year contender"/one championship. Had we not traded Perk, we would've won two championships, maintained the toughness/grit that defined and made us successful, and not drastically overpaid a Sally.
None of the draft picks he made were reaches. Which of those who turned out successful were risky, insightful picks? Bradley was touted to be comparable to Wall 12 months prior to draft. And our youth greatly benefited from learning from some of the best players the past two decades.
If Wallace/Jermaine/Shaq/Perkins bodies don't explode/collapse at the most inopportune times for 4 consecutive years, we have a dynasty on our hands. Especially after this offseason where everything was a homerun (and the only possible negative has been looking really good lately), I don't understand how anyone could possibly be calling for a new GM.
Absolutely absurd from spoiled idiots who expected to go 72-10. This team has already shown massive signs of improvement from the beginning of the year and they have not come even close to peaking. Ainge has earned 10 more years of job security as far as I'm concerned.
Revolution at last! It's time to clean Celtic management. Hell this team is only an experiment in futility anyway. You guys that want another ring will have to wait at least > 5 years for that and that's a conservative guess. Pierce, KG and Rondo's abilities have been wasted on 2nd rate players. Any good NBA Coach and Management Team would have had more than 1 ring with this group. I love Danny's contributions to the Celtics but has grown stale. Celtics love hanging on to failing stars. It has cost us for decades. The Celtics only had half the brains of the Jerry West era.
Ainge is a clown. McHale handed him a "5-year contender"/one championship. Had we not traded Perk, we would've won two championships, maintained the toughness/grit that defined and made us successful, and not drastically overpaid a Sally.
None of the draft picks he made were reaches. Which of those who turned out successful were risky, insightful picks? Bradley was touted to be comparable to Wall 12 months prior to draft. And our youth greatly benefited from learning from some of the best players the past two decades.
Perkins is so overrated on this site it's incredible. He has played horrible since getting traded.
Which available GM is out there that you think we should replace Danny with?
Otis Smith?Isiah Thomas?Scott Layden?ML Carr?
Why does it have to be a GM? And as far as Coach, Doc is what he was a 500 Coach. He surely doesn't get enough out of this team. We keep making the same mistakes over and over. Lack of rebounding energy, turn overs, less than average hustle, he can't scold the Team because it's a big love in there. Nobody on the Team is earning his $$.
No way we should even think about removing Ainge or Doc. They are both very good....and one of the many reasons for this is job tenure and relative security.
We had a 20 year hiatus from relevancy, and a parade of mediocre GMs and Coaches to go along with that run. We are now in year 6 of the KG era, and are still competitive - KG only comes back and signs that deal because of Doc. How many GMs had the summer Danny did, especially after losing Ray for half the money?
Why get rid of the GM who is good in the draft when the team is getting close to a rebuilding era?
because Danny is still always itching to pull the trigger on bad trades because he is constantly trying to prove he is smarter than Red was. Yes, he brought us a title, but he cost us at least 1, maybe 2 more.
someone add up all of Danny's personnel moves since he has been here (drafts, trades, free agent, letting players leave, etc). put a plus or minus beside each and see where we come out. double pluses (KG/Ray) and triple minuses (Perk) are allowed.
Why get rid of the GM who is good in the draft when the team is getting close to a rebuilding era?
because Danny is still always itching to pull the trigger on bad trades because he is constantly trying to prove he is smarter than Red was. Yes, he brought us a title, but he cost us at least 1, maybe 2 more.
someone add up all of Danny's personnel moves since he has been here (drafts, trades, free agent, letting players leave, etc). put a plus or minus beside each and see where we come out. double pluses (KG/Ray) and triple minuses (Perk) are allowed.
Dont compare the Perkins trade in weight to the KG/Ray moves. Just dont be that silly please.
Have whatever opinion you want about whether getting rid of perkins was a good idea, but dont compare it in significance to getting Kevin Garnett and Ray Allen.
Perkins was not this team's identity. Kevin Garnett was and continues to be.
Ainge is a clown. McHale handed him a "5-year contender"/one championship. Had we not traded Perk, we would've won two championships, maintained the toughness/grit that defined and made us successful, and not drastically overpaid a Sally.
None of the draft picks he made were reaches. Which of those who turned out successful were risky, insightful picks? Bradley was touted to be comparable to Wall 12 months prior to draft. And our youth greatly benefited from learning from some of the best players the past two decades.
Perkins is so overrated on this site it's incredible. He has played horrible since getting traded.
}and play pretty decent while he was here and this is not a DA questioning post he did what he had to do whithout any bech on that time...i hate to see perkk goes just like the next guy but at the time i said it was necesary sadly green went down....who knows..not us
Logged
Once a CrotorNat always a CROTORNAT 2 times CB draft Champion 2009-2012
someone add up all of Danny's personnel moves since he has been here (drafts, trades, free agent, letting players leave, etc). put a plus or minus beside each and see where we come out. double pluses (KG/Ray) and triple minuses (Perk) are allowed.
Perk trade is a plus, not a minus.
Logged
"The worst thing that ever happened in sports was sports radio, and the internet is sports radio on steroids with lower IQs.” -- Brian Burke, former Toronto Maple Leafs senior adviser, at the 2013 MIT Sloan Sports Analytics Conference
someone add up all of Danny's personnel moves since he has been here (drafts, trades, free agent, letting players leave, etc). put a plus or minus beside each and see where we come out. double pluses (KG/Ray) and triple minuses (Perk) are allowed.
Perk trade is a plus, not a minus.
Agreed with the way green looks as of late and how perk looks. Fab melo is a big wild card. | 2023-10-30T01:26:28.774034 | https://example.com/article/9057 |