Friday, December 28, 2012

US flights cancelled over bad weather: Voice of Russia

Gale force winds, tornadoes, heavy snowfalls and ice on roads have paralyzed traffic in various regions of the country.

More than 30 centimeters of snow fell out in the northeast of the country in just a few days.

Local weather services forecast severe snowstorms in Pennsylvania, New Jersey, New York and New England.

The current spell of cold weather has claimed a total of 12 lives.

Voice of Russia, Interfax

Source: http://english.ruvr.ru/2012_12_28/US-flights-cancelled-over-bad-weather/

tupac shakur sledge hammer tax day freebies madison bumgarner wnba draft tax day april 17

1 On 1 Tutoring | Internet and Businesses Online

Guys from around the world all have distinctive tastes in females. Some prefer ladies that have had related life experiences although other people pursue single ladies who possess a unique point of view and culture. It really is all a matter of taste and character as we are all one of a kind and unique. In looking to connect with girls from far flung locations, some guys have chosen to utilize mail order bride agencies. The concept of utilizing a locally based ?matchmaker? in a foreign nation is often a good notion, however every day males continue to get exploited and victimized by unscrupulous agencies. So what are a few of items it is best to look out prior to before signing up with an agency?

Nicely, the first issue anyone initially looks for when visiting?bridesire.com web page could be the images in the females. The distinction amongst the pictures on a regular on-line dating web page and a mail order bride web site is substantial in quite a few cases. The women that are sincerely seeking love on a web-based dating web site will share with you pictures taken by associates, members of the family or even themselves and they all have one particular issue in widespread, they?re genuine.

In comparison, the images on a mail order bride internet site are frequently taken by an expert photographer who has an highly-priced camera, lighting and editing gear to make the women appear their very best. It all comes across as feeling insincere or fake, as guys generally state that something ?just does not appear right?. Possibly its the truth that the girls are wearing bikinis or factor high boots with miniskirts within the pictures. Regardless of what it may possibly be, the entire factor quickly tends to make you really feel like you?re becoming ?conned?. Guess what?.in 99.9% with the situations, that you are and should you need any proof, simply do your homework. Should you visit YouTube and sort in ?Mail Order Bride Fraud? or visit Google and type ?profile fraud mail order brides?, you will have countless articles discussing this sleazy tactic.

Yet another thing you are able to do will be to register a blank profile on a mail order site that charges to send and acquire e-mail. You might be overwhelmed by how quite a few emails you get from ?women? who come across your profile extremely interesting although there exists no picture or details. I recently registered a blank profile on the major mail order bride web-site and inside 24 hours I had over 100 messages from gorgeous ladies! I wonder when the $10 charge to open up each and every e-mail had something to complete with it. It?s also essential to point out that I would spend an added $10 to send an e mail, which meant that the initial day I could have spent $2,000 in emails alone. Did I mention that emails would price added if there had been images attached!

Lots of the sleazy agencies offer you the alternative of sending a ?gift? towards the girls you are talking to by means of the web page. On the leading romance tour internet site, they presented guys the chance to send a woman in Cebu, Philippines 11 roses for $95 dollars. Keep in thoughts that the Philippines is actually a producing country so items price quite a bit much less there. So that you can see how insanely highly-priced this ?gift? was, I decided to appear on Google for florists in Cebu to view what the expenses had been for roses. Among the list of most highly-priced florists made available 50 roses for $70 dollars, so recognize that the ?gift? program is only an work to empty you wallet and bank account.

For much more information on rip-offs in the mail order bride market, visit plus size wedding dresses.

Source: http://1on1tutoring.net/internet-and-businesses-online/12/08/16/

kentucky wildcats oakland school shooting nike nfl jerseys katie couric barista university of kentucky ncaa

Wednesday, December 19, 2012

Washington Redskins give more than 1,000 toys during annual gift drive

? 2012 American City Business Journals. All rights reserved. Use of this Site constitutes acceptance of our User Agreement (updated 3/14/12) and Privacy Policy (updated 3/14/12).

Your California Privacy Rights.

The material on this site may not be reproduced, distributed, transmitted, cached or otherwise used, except with the prior written permission of American City Business Journals.

Ad Choices.

Source: http://feeds.bizjournals.com/~r/vertical_24/~3/cV16x9-0dHM/washington-redskins-give-more-than.html

ladainian tomlinson mark wahlberg pipa keystone xl sopa bill sopa and pipa piracy

Can I Still File a Personal Injury Claim If I Don't Immediately Notice ...

Last updated 2 hours 17 minutes ago

It?s very common for individuals to experience shock in the days following an auto accident. However, the ongoing effects aren?t just emotional?some physical injuries don?t show symptoms until long after an accident. Here?s a brief look at late-appearing auto accident injuries and how they affect personal injury claims:

Common Delayed Injuries
When you suffer an injury, your body produces endorphins to help relieve the pain. As a result, you may not experience pain until days after an accident. For example, whiplash is one of the most common late-appearing injuries. A concussion is an especially dangerous injury because it affects the brain; unfortunately, some of the repercussions don?t reveal themselves for months or even years after the fact.

Statute of Limitations
In Virginia, the statute of limitations for personal injury claims is two years. That means you have two years from the date of the accident to file a claim. If you wait longer than that, you forfeit your right to sue. In order to obtain the compensation you need to live a comfortable life, you should hire an attorney as soon after an accident as possible.

The Discovery Rule
Even if you don?t discover your injury until well after the two-year limitation period, you may still be able to file a personal injury claim. Like many other states, Virginia observes the Discovery Rule, which means that the statute of limitations doesn?t start until the victim discovers his injury. If you and your lawyer can prove that you suffered your injury during a particular incident, you may obtain compensation for your damage.

For more information about statutes of limitations and the discovery rule, contact the Auto Accident Law Firm of Kevin Paul Childers. We can help you obtain compensation for lost wages, medical bills, emotional harm, and other damages. Call our Woodbridge office today at (703) 659-1536 if you have any questions.

Disclaimer:
The materials available at this website are for informational purposes only and not for the purpose of providing legal advice. You should contact your attorney to obtain advice with respect to any particular issue or problem. Use and access to this website or any of the links contained within the site do not create an attorney-client relationship. The opinions expressed at or through this site are the opinions of the individual author and may not reflect the opinions of the firm or any individual attorney.

?

Source: http://www.kpchilderslaw.com/612289/2012/12/19/can-i-still-file-a-personal-injury-claim-if-i-dont-immediately-notice-my-injury.html

Lilit Avagyan Nashville TV Show VP debate drew brees drew brees sandusky Sam Champion

Saturday, December 15, 2012

Health Care - Acne, Fitness, Diabetes Center Advice and Tips Is ...

People who snore may be embarrassed about discussing the matter. So because no one talks about snoring, there is little widespread knowledge about how to alleviate it. Yet, this article is here to help you with just that, use the advice from this article and learn what you can do to rid yourself of snoring as you sleep.

Exercise your tongue regularly. It may sound comical, but you can actually exercise your tongue by sticking it in and out of your mouth. Stick your tongue out and then make it rigid. Then, point it in different directions. Make certain you are hitting all four points on the compass during the exercise. The muscles in your tongue will become toned and you will be less likely to snore.

Sleeping pills or alcohol can help you to sleep, but it?s not a good way to try to stop snoring. Both of these cause the muscles to relax a lot, including the ones in your throat, which means you will snore more, and more loudly than before. You should talk to a doctor about any trouble you have sleeping.

Adjust your time for eating routine if snoring is an issue. Have a small meal for dinner and eat it early. Eating rich foods, as well as dairy products, can lead to more mucus buildup. You should also try drinking tea with honey before you go to sleep to help ease any strain or tension contained in your throat.

Consider eating a tablespoon of honey before you go to bed. It is unclear as to why it seems to work, but many testify to honey?s effectiveness in reducing your tendency to snore. This is not really that surprising when you think of the myriad of other applications honey has in folk medicine.

To stop snoring, you must discover the reason you are snoring to begin with. For instance, certain health issues cause snoring and without getting them treated, it won?t go away. In fact, it could even get worse.

The proper amount of sleep can help to reduce your snoring. It is also important to maintain a sleep schedule that is consistent, in addition to getting enough sleep. Go to sleep and wake up on the same schedule every day of the week.

Quit smoking by any means necessary. Smoking any tobacco products will harm your respiratory system, resulting in serious health problems, not least of which includes chronic snoring. If you quit, your lungs and throat will heal and your health issues and snoring will lessen.

Try snoring strips to cut down on snoring and get a better night of sleep. A simple strip of adhesive paper will lie on your nose, pulling your nostrils up and allowing more fresh air to enter your airway. These nasal strips are used by certain pro athletes to increase their performance, so it?s worth trying them out!

Sleep on your side, not your back. Sleeping on your back causes your throat to relax and can cause your soft palate to drop. This means that you will snore even more. The optimal sleeping position for chronic snorers is on their sides, but any position beats sleeping face-up.

Just as you learned from the beginning of this article, not that many people discuss the subject of snoring. You can now feel more comfortable discussing snoring as it will be a thing of the past once you use the tips you?ve read here!

VN:F [1.9.21_1169]

Rating: 0.0/10 (0 votes cast)

VN:F [1.9.21_1169]

Source: http://www.healthcarecenteradvice.com/2012/12/15/is-snoring-keeping-you-or-a-loved-one-awake-at-night-try-these-simple-solutions-3/

john mccain game changer selection sunday corned beef recipe time change rpi dst

Windows Phone?s real test starts now

"We all heard these booming noises, and we started crying"The Associated Press reports that 27 people, including 18 children, were killed on Friday morning in a school shooting at Sandy Hook Elementary in Newtown, Connecticut. Much remains unknown about the mass shooting, which is already being described as one of the worst in American history. But a picture of terror and tragedy is slowly emerging from news reports on the ground. ...

Source: http://news.yahoo.com/windows-phone-real-test-starts-now-185103817.html

rough riders joy division norco rand paul detained asexual jim carrey san francisco chronicle

Friday, December 14, 2012

Boehner: White House willing to "slow-walk" up to "fiscal cliff"

WASHINGTON (Reuters) - Speaker of the U.S. House of Representatives John Boehner on Thursday again rejected President Barack Obama's demand for increased power to raise the U.S. debt and charged that the White House seems willing to "slow-walk our economy right up to the 'fiscal cliff.'"

The White House and Congress face a year-end deadline to avert the so-called fiscal cliff of automatic tax hikes and budget cuts that experts fear could plunge the nation into another recession.

"The president wants to pretend spending isn't the problem. That's why we don't have an agreement" to reduce the U.S. debt, Boehner, the top Republican, told a news conference.

In underscoring the stalemate in negotiations, Boehner reiterated his opposition to giving Obama the power to raise the U.S. debt limit without congressional approval.

"Congress is never going to give up our ability to control the purse," Boehner said. "And the fact is, is that the debt limit ought to be used to bring fiscal sanity to Washington."

Boehner seemed to brush off speculation fanned by Democrats that his concern about keeping his job was undermining efforts to cut a bipartisan deal.

"I'm not concerned about my job as speaker. I'm concerned about our kids and our grand kids," Boehner said.

Obama is expected to discuss the "fiscal cliff" later in the day, likely cranking up pressure on Republicans to accept increased tax rates on the wealthy as part of any deal.

Boehner said it's up to the White House to offer a balanced package.

"Republicans want to solve the problem and get this spending line down. The president wants to pretend spending isn't the problem. That's why we don't have an agreement," Boehner said.

"Unfortunately, the White House is so unserious about cutting spending that it appears willing to slow-walk our economy right up to the 'fiscal cliff,'" Boehner added.

(Reporting by Thomas Ferraro, David Lawder, Patricia Zengerle, Richard Cowan and Rachelle Younglai; Editing by Paul Simao)

Source: http://news.yahoo.com/boehner-white-house-seems-willing-slow-walk-over-162842595--business.html

china gdp dont trust the b in apartment 23 johnny damon kirk cameron news 10 hillary rosen j.k. rowling

FCC gives Samsung's Galaxy Note 10.1 LTE edition the nod, US LTE not included

FCC gives Samsung's Galaxy Note 10.1 LTE edition the nod, forgets the LTE part

South Koreans were given preferential treatment again last month, as Samsung released the LTE variant of the Galaxy Note 10.1 in its native land. It looks like this period of exclusive access will soon end, however, as the 4G-equipped version of the slate has dropped by the FCC to pick up a round of approvals. Codenamed SHV-E230S and showing a global (read: non-US) LTE logo on the back panel, the US regulator cleared WiFi, Bluetooth, GSM and WCDMA (3G) connectivity options. Given the absence of US LTE radios and the non-US model number, it's quite likely that this is just another variant of the Korean version. Unfortunately, this means there isn't much time for it to launch stateside if it wants a spot under indoor evergreens, so don't get those hopes up.

Filed under: ,

Comments

Via: Wireless Goodness

Source: FCC

Source: http://feeds.engadget.com/~r/weblogsinc/engadget/~3/OhpRqOpsBwM/

apple store down apple live blog ohio primary cell phone jammer g8 summit netanyahu aipac

In search of the world's oldest cave etching

I'M DRIVING across South Australia's featureless but iconic Nullarbor Plain when suddenly the red earth falls away into a black abyss. "Dramatic really is the word for it," says Keryn Walshe.

Fifty metres wide and 25 metres deep, the sinkhole is a gateway to the mysterious Koonalda caves.Walshe, an archaeologist from the South Australian Museum, is leading a group of researchers and members of the Mirning people, the traditional Aboriginal owners of the land, into the caves. It has taken us 6 hours to drive here, after flying in from Adelaide, the nearest city, 900 kilometres away.

We have come to see strange wall markings that may have been a tactile code left by flint miners during the last ice age. The mine might be among the oldest in the world, as may the markings. The flint has clearly been cut away in numerous places and worked into tools, and ash deposits from fires show people have been coming here for tens of thousands of years.

For the Mirning, the intrigue is deepened by stories of a fearsome snake called Ganba that lived in the caves, making the faint hissing sounds we can hear.

A ladder takes us down to the cave floor, which drops steeply away from us, transforming into a glorious cavern. We turn a corner and the last of the daylight disappears. "You better get a photo of that," says one of the researchers, pointing at a mound of rocks that reduces the space in front of us to a crevice. "Behind that is where the markings are."

Following us are Robert Zlot and Mike Bosse from the CSIRO Autonomous Systems Lab in Brisbane. They look undeniably silly, each holding what looks like a dangling jack-in-the-box. In fact, it's the world's most versatile 3D scanning device, named Zebedee after the children's TV character.

"Nobody thought it was possible," says Bosse, who created Zebedee with Zlot. Until now, 3D scanners needed an independent fix on their location - extremely difficult in environments like this where GPS doesn't reach and surveys are hard.

"The smarts are in the software," says Zlot. Zebedee figures out where it has been by comparing scans as it goes along. It can scan the entire cave in the time it takes us to walk around it, sweeping the surfaces as it flops on its spring.

And then we see the markings. Wavy parallel lines known as flutings swirl around the contours of the damp, powdery rock. Some seem made by fingers, others are sharper and appear scratched. They could have been made using the claw of a dead animal, sticks or flint, Walshe says. Confusingly, though, some may have been made by trapped animals.

No one knows what they signify. Walshe says they are not likely to be art, in any modern sense of the word. Since they are in pitch darkness, they could be tactile signs, telling ancient Aboriginal miners where to go or where the best flint was. "Or they could be something as simple as 'hey, I was here'," she says.

Zebedee's scans will be combined with photos taken by George Poropat, also from CSIRO. The scanner's software will recognise the surfaces in those photos to create a 3D model with 0.25-millimetre resolution.

"The flutings are saying something, as they are repetitive in style and placement," says Walshe. "Those who made the marks must have believed that others who saw them understood the meaning." With the 3D scans, the team will be able to measure them, look for patterns and share the images with specialists around the world. They will even try to figure out the demographics of the people who made the marks by trying to figure out the size of the fingers, Walshe says.

Squeezing through gaps so narrow we can't turn our heads, we come to some 6-metre trenches dug by archaeologists in the 1960s. "It's madness... They had to do this by candlelight," Walshe says.

She's visibly excited when she finds chunks of ash in the deep layers of the trenches. Researchers in the 60s dated human activity here to 31,000 years ago. Limited ash samples and assumptions about Aboriginal migration meant that wasn't accepted at the time, but there's evidence nearby of human activity as far back as 41,000 years ago. If Walshe confirms this earlier date, it would mean people migrated the length of the continent far faster than was thought.

After 7 hours, the cave has been modelled, samples collected and we start the long drive back to the nearest roadhouse. By the time we have unpacked the SUV, Bosse has already created an interactive 3D map of almost the entire cave.

That night the cave's mysteries remained, but the answers are waiting to be decoded by our modern-day tools.

Michael Slezak travelled with Inspiring Australia

If you would like to reuse any content from New Scientist, either in print or online, please contact the syndication department first for permission. New Scientist does not own rights to photos, but there are a variety of licensing options available for use of articles and graphics we own the copyright to.

Have your say

Only subscribers may leave comments on this article. Please log in.

Only personal subscribers may leave comments on this article

Subscribe now to comment.

All comments should respect the New Scientist House Rules. If you think a particular comment breaks these rules then please use the "Report" link in that comment to report it to us.

If you are having a technical problem posting a comment, please contact technical support.

Source: http://feeds.newscientist.com/c/749/f/10897/s/2692fd06/l/0L0Snewscientist0N0Carticle0Cmg216289540B70A0A0Ein0Esearch0Eof0Ethe0Eworlds0Eoldest0Ecave0Eetching0Bhtml0Dcmpid0FRSS0QNSNS0Q20A120EGLOBAL0Qonline0Enews/story01.htm

merle haggard ladainian tomlinson mark wahlberg pipa keystone xl sopa bill sopa and pipa

Thursday, December 13, 2012

The Future of the Web and Quality Standards | SEO and Content ...

Google Search ResultsOver the past few years, Google has shaken the world of internet marketers over and over again. They (Google) have made changes to their search?algorithms?in an effort to weed out poor quality search engine results. Search engine results are what the user is served when making a search for something like their local dentist. In the past, marketers and website developers found ways to game the system, making it easy for their low quality site, filled with information that doesn?t serve the user, rank towards the top of the search engine results. Google and other major search engines have been, and will continue to improve their algorithms in order to serve their daily users the best information possible. Will your dental website survive the evolving standards that these search engines are requiring from sites?

Building High Quality Websites

Technology evolves at an astonishing rate. That brand new smart phone you bought will be out of date in six months. Web technology is evolving as well, and if your website is running off of yesterday?s code, it might not meet the standards that search engines require today. An example of out dated website development would be a Flash animated website. These sites were extremely popular up until two years ago because they are generally beautiful, animated websites. Unfortunately, search engines cannot read the content on those sites well, making the business running it virtually invisible in search. Another problem with Flash website design is that they are generally slow, and drain a lot of memory from your computer. To make things worse, Apple saw the future of the mobile web by refusing to to support Flash websites on their mobile technology. As the iPhone and iPad continued to increase in popularity, we have seen Flash websites begin to disappear.

At TrustWorkz, Inc, we build mobile responsive websites for dentists because they perform well across mobile technology as well as traditional desktop computers. We made the decision to commit to only building mobile responsive websites around 7 months ago when both Bing and Google said that they preferred mobile responsive website design when it came to meeting the needs of mobile technology.

When rebuilding your dental website, it?s important to make sure that your developer is building your site with loading speed in mind as well. Have you ever been to a website that takes forever to load, and return to Google to search for another site because of how long it took for a page to appear? You?re not alone! Slow websites generally mean low quality. It?s not efficient, and it?s not what users are looking for when searching the web. For this reason, Google gives brownie points to sites that load quickly. Our development team makes website load time a priority for each and every dental practice/small business.

Search Engine Optimization Now and in the Future

Last week, Raven Tools (whom we proudly use) announced that they were shutting down their Rank Tracker tool due to the data not being completely accurate. This, in part, was due to the fact that the information for the Rank Tracker tool was scraped data, and not from Google. The data is considered to be unauthorized Google data, and many popular SEO tools use something similar for their tools. It just so happens that Raven decided to prepare for the future, and make the tough change now rather than later.

At TrustWorkz, Inc., we believe that taking the high road now is the best way to position our clients? businesses for internet success one, two, or five years from now.

Search engine?optimization?(SEO) for current and future environments means that websites not only need to grab the attention of search engines like Google, but they need to add value to potential customers and web users as well. One of the many things that makes TrustWorkz, Inc. different from our competitors is that we create original content for each of our dental websites. That means that none of our clients will ever have identical content on their websites as anyone else on the web. Many dental marketing companies claim to produce original content for their clients, which is partially true. What they don?t tell you is that the content that they produce is shared over their network. Unfortunately for their clients, this practice still creates duplicate content across the internet which is an offense that Google will eventually take action against.

Our high quality content is optimized with internal links, keyword targets, and more markups that Google and internet users are both looking for when searching the web. At the end of the day, we have business longevity in mind for your dental practice by not only taking the high road in terms of search engine?optimization, but by creating useful content for your potential and current patients as well.

How Should You Invest in the Future?

Investing in your web presence today means that your dental practice/business will have a dominant strategic position over your?competitors?who chose to ignore high quality optimization when your grabbed it by the tail.

Source: http://trustworkz.com/future-web-and-quality-standards/

tangled ever after kansas state last house on the left last house on the left rich forever mixtape blow the unit

Wednesday, December 12, 2012

Buying Real Estate To Build Your Bottom Line

There are a lot of safe ways to invest in the real estate market, but you need to be careful because there are even more ways that you could make a bad investment. Before ending up with big losses or buying a house for well more than the going rate, continue on to the article below for some great home buying advice.

If you have a specific neighborhood in mind, you should familiarize yourself with other houses in the area. You don?t always want to shoot for the biggest house in any particular neighborhood. The reason is because you will not get back the money you put into the home when there are homes that are less expensive in the same area.

If you are looking to buy a new home, remember that there are more important things than decoration. Your decision as to whether you will purchase a home should be based on the quality of its build and your requirements for sizing. If you buy a home primarily because it has structural details that appeal to you, you may fail to recognize critical flaws that can end up costing you thousands of dollars down the road.

If you want to have a good return on your property, try to do some remodeling. As you finish the work, you will be rewarded with an immediate increase in the value of your home. Sometimes your value will go up more than what you invested.

Always ask real estate agents about the length of time they have resided in the area you are considering. If the agent has only been in the area for a short time, they may not be as aware of the neighborhoods, roads, and restrictions in the community as someone else might be. Ideally, you should select an agent that has been a resident of the area for a minimum of ten years.

If you are trying to purchase a home but the seller rejected your offer, do not worry, there may be other options or methods you can utilize to make the home more affordable. Explore options such as incorporating closing costs into the deal or asking for improvements to the home, prior to purchase.

Research market conditions before you begin searching for local real estate investments. Check websites including City-data.com to find out about foreclosed homes, median selling prices, housing backlogs and the average time on the market for homes in your Zip code. Other things you may want to investigate are local unemployment rates, income levels and schools. Sometimes, a great location and product can override local trends.

The information that has been provided in this article should have taught you that purchasing a new property may not be as difficult as you thought if you choose to do proper research and are prepared. Utilize the advice in this article, and start making intelligent real estate purchasing decisions.

Source: http://louieblog.sagorena.com/2012/12/12/buying-real-estate-to-build-your-bottom-line/

presidents george washington russell westbrook horsetail falls ice t downton abbey new york knicks

Colombia's Congress passes controversial military justice reform (reuters)

Share With Friends: Share on FacebookTweet ThisPost to Google-BuzzSend on GmailPost to Linked-InSubscribe to This Feed | Rss To Twitter | Politics - Top Stories News, RSS and RSS Feed via Feedzilla.

Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/270110014?client_source=feed&format=rss

michael jordan checkers imbibe msg network ray j anthony shadid gary carter

Study paves way to design drugs aimed at multiple protein targets at once

Dec. 12, 2012 ? An international research collaboration led by scientists at the University of North Carolina School of Medicine and the University of Dundee, in the U.K., have developed a way to efficiently and effectively make designer drugs that hit multiple protein targets at once.

This accomplishment, described in the Dec. 13, 2012 issue of the journal Nature, may prove invaluable for developing drugs to treat many common human diseases such as diabetes, high blood pressure, obesity, cancer, schizophrenia, and bi-polar disorder.

These disorders are called complex diseases because each have a number of genetic and non-genetic influences that determine susceptibility, i.e., whether someone will get the disease or not.

"In terms of the genetics of schizophrenia we know there are likely hundreds of different genes that can influence the risk for disease and, because of that, there's likely no single gene and no one drug target that will be useful for treating it, like other common complex diseases," said study co-leader, Brian L. Roth, MD, PhD, Michael J. Hooker Distinguished Professor of Pharmacology in the UNC School of Medicine, professor in the Division of Chemical Biology and Medicinal Chemistry in the UNC Eshelman School of Pharmacy, and director of the National Institute of Mental Health Psychoactive Drug Screening Program.

In complex neuropsychiatric conditions, infectious diseases and cancer, Roth points out that for the past 20 years drug design has been selectively aimed at a single molecular target, but because these are complex diseases, the drugs are often ineffective and thus many never reach the market.

Moreover, a drug that acts on a single targeted protein may interact with many other proteins. These undesired interactions frequently cause toxicity and adverse effects.

"And so the realization has been that perhaps one way forward is to make drugs that hit collections of drug targets simultaneously. This paper provides a way to do that," Roth said.

The new way involves automated drug design by computer that takes advantage of large databases of drug-target interactions. The latter have been made public through Roth's lab at UNC and through other resources.

Basically, the researchers, also co-led by Andrew L. Hopkins, PhD in the Division of Biological Chemistry and Drug Discovery, College of Life Sciences, at the University of Dundee, in Scotland, used the power of computational chemistry to design drug compounds that were then synthesized by chemists, tested in experimental assays and validated in mouse models of human disease.

The study team experimentally tested 800 drug-target predictions of the computationally designed compounds; of these, 75 percent were confirmed in test-tube (in vitro) experiments.

Drug to target engagement also was confirmed in animal models of human disease. In a mouse model of attention deficit hyperactivity disorder (ADHD), mice missing a particular dopamine receptor engage in recurrent aberrant behaviors similar to what is seen in ADHD: distractibility and novelty seeking. "We created a compound that was predicted to prevent those recurrent behaviors and it worked quite well," Roth said.

The researchers then tested the compound in another mouse model where a particular enzyme for a brain neuropeptide is missing. Distractibility and novelty seeking also are behavioral features in these animals. And the drug had the same effect in those mice.

The new drug design process includes ensuring that compounds enter the brain by crossing the blood-brain barrier. These, too, were tested successfully in live animals.

According to Roth, pharmaceutical company chemists had suggested that the objective of a drug hitting multiple targets simultaneously is impossible and unlikely to succeed. "Here we show how to efficiently and effectively make designer drugs that can do that."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:


Story Source:

The above story is reprinted from materials provided by University of North Carolina Health Care.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. J?r?my Besnard, Gian Filippo Ruda, Vincent Setola, Keren Abecassis, Ramona M. Rodriguiz, Xi-Ping Huang, Suzanne Norval, Maria F. Sassano, Antony I. Shin, Lauren A. Webster, Frederick R. C. Simeons, Laste Stojanovski, Annik Prat, Nabil G. Seidah, Daniel B. Constam, G. Richard Bickerton, Kevin D. Read, William C. Wetsel, Ian H. Gilbert, Bryan L. Roth, Andrew L. Hopkins. Automated design of ligands to polypharmacological profiles. Nature, 2012; 492 (7428): 215 DOI: 10.1038/nature11691

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/deFlpBdvRVc/121212134058.htm

Blue Moon August 2012 Eddie Murphy Dead michelle obama robin roberts Democratic National Convention 2012 myocardial infarction What Is Labor Day

Monday, December 10, 2012

van Persie shows no mercy

Despite long spells of City dominance, Manchester United took a crucial three points from the Etihad Stadium on Sunday. Two first half goals from Wayne Rooney capped by a stoppage time winner from Robin van Persie saw the Red Devils defeat their inter-city, 3-2.

After 15 minutes of absorbing a strong start from their hosts, Manchester United again showed their best moments are capable of winning this year?s Premier League. Yet an early double Rooney was not enough to stave off a shootout, with a second half siege from Manchester City producing goals from Yaya Tour? and, in the 86th minute, Pablo Zabaleta.

Luck shined on United in the final minutes as a free kick to the right of the area deflected off Samir Nasri in City?s wall. The resulting ball curved into the left side of Joe Hart?s net, giving United full points from their rival.

It was exactly the type of performance we?ve come to expect in big games from this Manchester United team: uneven, at times meek, but in the moments that mattered most, precisely executed. ?While?last year?s Manchester Derbies hinted City may be immune to United?s potent attack (City outscoring their neighbors 7-1), this year United has stuck the first major blow in the Premier League title race.

With the win, the Red Devils sit six points clear in England.

Man of the Match:?While the second goal was one most players should finish, few could replicate?Wayne Rooney?s contributions to the opener. He clearly deserves credit for a shot which, pulled back across his body, froze Joe Hart as it rolled just inside the left post from 18 yards. But the shot would have never gotten off were it not for a deft touch on a hard-hit pass from Ashley Young, Rooney opening is right foot to perfectly trap a ball into the space he needed to get clear of three closing defenders.

Despite spending most of the season in the shadow of Robin van Persie, Rooney has quietly put up a prolific start to the season. After today?s tallies, the United talisman is up to six goals and seven assists in league action. Fourteen goals and 16 assists (his current pace) would be a spectacular year for the ever-evolving star.

Threesome of knowledge: What we learned

United was built for this: ?Against the run of play? was the common refrain after Manchester United opened their account. City had looked better, the analysis held, forgetting United always looks like this in big games.

Through most of a Premier League season, United?s skill on the ball can dominate games while the Red Devils play some of the best soccer in the world. But against teams like City and Chelsea, United have often conceded control with the hope their speed and execution will provide them with decisive chances in transition.

That?s exactly what happened today. When David de Gea came of his line to claim a through ball in the 15th minute, his first instinct was to get the ball back into play as soon as possible. A rolled pass to Patrice Evra, a chip to Ashley Young, a chest pass from Robin van Persie, and Young is free. Within seconds, the ball is in the back of Joe Hart?s next, all built off an innocuous pass from De Gea.

This is how United will win big games. Only Chelsea can match their skill in attack. Nobody can match their speed, depth, or variety.

City may have been the better side in the first quarter hour, but I doubt Alex Ferguson was worried about it.

Roberto Mancini?s tempting fate:?With Manchester City flaming out of Europe after finishing last in their Champions League group, some contend manager Roberto Mancini?s not long for the job at the Etihad. Today, Mancini stoked those flames.

He deserves credit for helping to bring his team back, but a series of curious lineup decisions are sure to draw questions:

  • Mario Balotelli started over Carlos Tevez and was then removed after trying a backheel. If you?re not prepared to live with Balotelli?s?idiosyncrasies, don?t start him. Even if you?re fine with his theatrics, the contention Balotelli should start a Manchester Derby over T?vez is difficult to defend.
  • Matija Nastasic continues to start at left-center half over Joleon Lescott. That?s defensible enough, even if breaking up the central defense tandem that won last year?s Premier League is problematic. But when Vincent Kompany got hurt and Kolo Tour? came on over Lescott, you started to wonder what Lescott?s done to fall so far in Mancini?s regard.
  • Is there ever a reason to take Yaya Tour? off and leave Barry on? That?s what happened in the 84th minute as Mancini brought Eden Dezko on. Perhaps fitness was a concern.

Moments, not spells:?Perhaps it?s the elevation of all things Barcelona that has led us to revere spells of control over moments of execution. You would have thought Inter Milan?s 2010 Champions League title would have dissuaded us of the notion, but it may not be that simple. There is something innately logical about assuming the team with the ball is in control, even if that control is often inconsequential.

This is why critics have often undervalued United?s recent teams. They often look second best. They don?t control play as often as other teams. Their midfield seems thin and undermanned. By the standards we?ve come to pursue in the modern, midfield-centric game, United is lacking.

Like Jos? Mourinho as he bossed Inter to that Champions League title (beating Barcelona along the way), Ferguson understands the leverage in those moments of transition where an attacking team can have a rare absolute advantage. In getting players like Antonio Valencia, Ashley Young and Shinji Kagawa (out injured on Sunday), he?s built his team to maximize those moments.

On Sunday, that philosophy earned United a crucial win. Maybe they didn?t control the match, but they control the points.

Packaged for takeaway

  • Rio Ferdinand was hit above the left eye by a coin thrown from the Eithad stands as he celebrated United?s third goal. With blood trickling down his face, it was initially unclear he?d be able to finish the game?s final minutes. Just a reminder: It?s still within the power of the crowd?s worst person to ruin a classic match.
  • Jonny Evans appeared to strain his right hamstring while being taken down by Balotelli in the first half. He had to come off for Chris Smalling.
  • David De Gea, who may have only started because Anders Lindegaard?s partner went into labor before the game, gave a strong performance. Against a City team that doesn?t rely on crossing, De Gea should probably start, regardless.
  • It was another game that worked against Joe Hart?s best goalkeeper in the world case. Then again, he?s not the one making it.

Source: http://prosoccertalk.nbcsports.com/2012/12/09/manchester-city-vs-manchester-united-result-2012-english-premier-league/related/

49ers anne hathaway mike brown earthquake bcs rankings world war z When Is Veterans Day 2012