Friday, April 26, 2013

REC10 Wireless Range Extender Fixes Your Crappy Wi-Fi Signal


If you live in a home larger than a single room, chances are you've experienced Wi-Fi reception issues before. We've offered several DIY solutions in the past, but those only go so far in larger homes with signal-killing walls. The Amped Wireless REC10 powers through those impenetrable corners of your home so you can actually get internet access everywhere.

I live in a large apartment with a roommate, so it isn't huge but it's big enough that the Wi-Fi just won't make it to my bedroom without causing significant dropouts. I'd repurposed an old Airport Express to extend the signal, which worked fine, but the speeds could've been a bit better. After implementing the REC10, however, the signal made it right through the Wi-Fi-killing wall no problem and gave me the same speeds I could expect when sitting in the living room, much closer to the router.

The REC10 connects to your existing Wi-Fi router wirelessly. You don't have to run an ethernet cable to it, like I had to with my AirPort Express. Setup isn't too difficult, either. You just connect to the REC10, choose the network you want to extend, provide the Wi-Fi password and fill in a few other settings. When you're done, you'll have a new extended network to connect to in the formerly Wi-Fi-less corners of your home. Of course, the REC10 won't work miracles. You need to put it somewhat near the router. I was actually able to place it fairly far away?in an area that received poor Wi-Fi reception normally?and it extended my network just fine. That said, if you're attempting to extend your network over a long range you may need more than one little gadget.

Overall, I was really surprised by how effectively the REC10 boosted my Wi-Fi signal. I tried it assuming it wouldn't manage to solve my Wi-Fi problems, but it did. If you're stuck with a crappy signal and DIY options aren't doing the trick, give this thing a try. It's pretty powerful for such a tiny little thing.

Amped Wireless REC10 High Power 600mW Compact Wi-Fi Range Extender ($70) | Amazon

Source: http://feeds.gawker.com/~r/lifehacker/full/~3/aec7Q3e8tGw/rec10-wireless-range-extender-fixes-your-crappy-wi-fi-s-481093435

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Metal detectors promised for Moscow track worlds

MOSCOW (AP) -- A top official for Russia's athletics federation says metal detectors will be used at the track and field world championships in Moscow in August.

Concerns about safety increased after last week's deadly bombings at the Boston Marathon.

General secretary Mikhail Butov told The Associated Press on Thursday that metal detectors will be set up at the entrances to Luzhniki Stadium, where all events except the marathon will be held.

He says the marathon presents less of a security challenge than in Boston because the one in Moscow will be four circuits of a course from the Kremlin to the stadium area.

Source: http://news.yahoo.com/metal-detectors-promised-moscow-track-174449798.html

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New grass hybrid could help reduce the likelihood of flooding

Apr. 25, 2013 ? A collaboration of plant and soil scientists from across the UK has shown a grass hybrid species could help reduce the impact of flooding.

The BBSRC-funded scientists, from Rothamsted Research, the James Hutton Institute, Institute of Biological, Environmental and Rural Sciences (IBERS) at Aberystwyth University, Lancaster University and the University of Nottingham, used a hybridised species of grass called perennial ryegrass (Lolium perenne) with a closely related species called meadow fescue (Festuca pratensis).

They hoped to integrate the rapid establishment and growth rate of the ryegrass with the large, well developed root systems and efficient water capture of the meadow fescue.

Over two years of field experiments in the south west the team demonstrated that the hybrid, named Festulolium, reduced water runoff from agricultural grassland by up to 51 per cent compared to a leading UK nationally-recommended perennial ryegrass cultivar and by 43 per cent compared to meadow fescue.

It is thought the reduced runoff is achieved because Festulolium's intense initial root growth and subsequent rapid turn-over, especially at depth, allows more water to be retained within the soil.

The hybrid grass also provides high quality forage with resilience to weather extremes, making the grass doubly useful to farmers.

Dr. Kit Macleod, catchment scientist at the James Hutton Institute and one of the authors of the paper, said: "Hybrid grasses of this type show potential for reducing the likelihood of flood generation, whilst providing pasture for food production under conditions of changing climate.

"In areas with similar climate and soils, then there is potential for reducing the likelihood of flood generation based on increased soil water storage within a river's catchment."

Professor Douglas Kell, Chief Executive of BBSRC, said: "We usually think of improving food crops solely in terms of traits such as the yield and quality of the food itself, and apart from root crops such as potatoes and carrots these are easily visible, above-ground traits. However, there is increasing recognition that the health and utility of plants can be greatly enhanced by improving below-ground traits such as root growth.

"This is a superb example of that reasoning, and a hugely important advance resulting from decades of fundamental BBSRC-supported work on the hybridisation of Lolium and Festuca (Fescue) species. I am sure that we shall see a continuing resurgence of interest in root biology, which findings such as this are sure to promote. The enormous savings that will be possible by mitigating flooding through planting grasses such as these dwarf any possible cost of producing them."

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The above story is reprinted from materials provided by Biotechnology and Biological Sciences Research Council.

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Journal Reference:

  1. Christopher (Kit) J. A. Macleod, Mike W. Humphreys, W. Richard Whalley, Lesley Turner, Andrew Binley, Chris W. Watts, Leif Sk?t, Adrian Joynes, Sarah Hawkins, Ian P. King, Sally O'Donovan, Phil M. Haygarth. A novel grass hybrid to reduce flood generation in temperate regions. Scientific Reports, 2013; 3 DOI: 10.1038/srep01683

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

Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/dM2PU6pN6mQ/130425103314.htm

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Booze-Tracking Bluetooth Breathalyzer Counts Down Your Return To Sobriety

An experienced imbiber has a pretty good idea of when they'll return to the land of the sober based on what type, and how much hooch they've consumed. But if you need a more detailed ETA on when you might be able to drive, walk, or even stand again, the BACtrack breathalyzer connects to a smartphone app for a more detailed analysis of your condition. More »
    


Source: http://feeds.gawker.com/~r/gizmodo/full/~3/s4H8jvmqIsw/booze+tracking-bluetooth-breathalyzer-counts-down-your-return-to-sobriety

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free ebook downloads | ebooks free online Creating Shareholder ...

Creating Shareholder Value: A Guide for Managers and Investors
Free Press | 1997-12-01 | ISBN: 0684844109 | HTM | 224 pages | 3 mb
The ultimate test of corporate strategy, the only reliable measure, is whether it creates economic value for shareholders. Now, in this substantially revised and updated edition of his 1986 business classic, Creating Shareholder Value, Alfred Rappaport provides managers and investors with the practical tools needed to generate superior returns. After a decade of downsizings frequently blamed on shareholder value decision making, this book presents a new and indepth assessment of the rationale for shareholder value. Further, Rappaport presents provocative new insights on shareholder value applications to: (1) business planning, (2) performance evaluation, (3) executive compensation, (4) mergers and acquisitions, (5) interpreting stock market signals, and (6) organizational implementation. Readers will be particularly interested in Rappaport?s answers to three management performance evaluation questions: (1) What is the most appropriate measure of performance? (2) What is the most appropriate target level of performance? and (3) How should rewards be linked to performance? The recent acquisition of Duracell International by Gillette is analyzed in detail, enabling the reader to understand the critical information needed when assessing the risks and rewards of a merger from both sides of the negotiating table.

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Source: http://www.99980.net/business/ebooks-free-online-creating-shareholder-value-a-guide-for-managers-and-investors/

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Thursday, April 25, 2013

While driving, texting by voice no safer than by hands: Study

A new study says voice texting is just as dangerous as using your hands (AP)Going hands-free on your mobile device to send a text while driving is no less dangerous than the traditional method, according to a new university study.

In fact, the risk is nearly identical, with both ways cutting reaction time for drivers in half.

Christine Yager, who led the study for the Texas A&M Transportation Institute, said the research was "a useful step, and we?re eager to see what other studies may find."

It was conducted as part of National Distracted Driving Awareness Month.

A number of unsettling statistics have come out recently as part of the ongoing effort to help reduce behavior called ?distracted driving.?

In March, a study found that adults are far more likely to text while driving than teens. Another study released in early April found that daydreaming while driving results in thousands of fatal car accidents each year.

For its study, TTI tested 47 drivers on a closed course to measure their reaction times while using the two most popular voice-controlled texting apps, Siri and Vlingo.

The drivers went around the course three times: once while not using their phone; once texting with their hands; and once texting by voice. A stoplight appeared at random intervals, and the researchers compared how long it took the drivers to respond.

?Driver response times were significantly delayed no matter which texting method was used. In each case, drivers took about twice as long to react as they did when they weren?t texting,? an excerpt from the study reads.

The study had some other interesting findings. Drivers reported, for instance, that they felt safer when texting by voice compared with their hands. And it found that the latter was slightly faster than texting by voice, along with posing the same general amount of risk.

The study did not specify why texting by voice posed the same risk. But several factors could explain the results, including the fact that an individual must still look at the phone to read and send his or her text message, even if using a "hands-free" device.

Source: http://news.yahoo.com/blogs/sideshow/voice-activated-texting-while-driving-no-safer-using-022223915.html

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Local Entrepreneur Brings Joy of TapSnap ... - Franchising.com

Local resident Ben Bender had always nursed entrepreneurial aspirations.?

NORTH VANCOUVER, BC - April 24, 2013 /24-7PressRelease/ - Local resident Ben Bender had always nursed entrepreneurial aspirations. Now working in purchasing for a pharmaceutical company, he'd been under constant threat of downsizing at his previous job, which only underscored the need for something more self-sufficient. "I wanted to look out for myself and my family, my wife and my two little girls," said Bender.

The hunt began. He didn't want just any business. For one, it had to be part-time on evenings and weekends to fit with his current full-time position, and he really wanted something that would be fun and make people happy, because life is already too short.

He came across a completely new franchise called TapSnap, the brainchild of a Vancouver, Canada company DVDNow Kiosks, that specializes in kiosks.

"It's something fun, that gives back to people and creates memories," he said.

Launched this April at over two dozen locations across North America, TapSnap is the special event photo booth reinvented as an open-concept, high-tech phototainment system that is instantly connected to social media. It allows event guests to take their pictures with the touch of a finger on the giant 42-inch multi-touch screen, alter their photos with digital props and drawings, and share instantly with social media networks or via email.

For Bender, it was an opportunity for resurrection. His grandfather Benjamin Kadransky founded Mid-City Camera in the 1940's and a second business Fotorama, both in downtown Philadelphia. His father Joel Bender also owned and managed the business for decades and was a fixture in the city.

"Digital killed the family business," he said. For many years, the businesses thrived, but with the onset of digital and the big box stores, eventually they sold the business."TapSnap brings us full circle," said Bender.

Best of all was the moment when he called several family members to say: "The Benders are back in the photography business."

And it is a family business again. Bender's sister Ellyn Cohen is the VP of sales for his local franchise which is serving Philadelphia and the surrounding region.

They've teamed up with several meeting planning companies, such as EBE and Roberts Event Group, who intend to use him as a supplier for their private and corporate events.

"The meeting planners love it, because many similar products don't work for the corporate market. With TapSnap, there's no booth, which eliminates a lot of liability issues because it's open concept, and the sophisticated look of the machine and small footprint means it fits in well at any venue," said Bender. "Plus it gives their event social media clout because guests share pictures online while the event is still happening."

He adds that when the event is over, the pictures and online photo galleries remind attendees what a fun time they had while giving the host an important record of the event, with data and information about the people who attended.

Already brother and sister team is tearing up the wedding and bar mitzvah circuit with many events in the works and there's no rest in sight.

The last week of April is chock-a-block full of events that include a cause very close to Bender's heart, a charity gala for the Leukemia and Lymphoma Society of Eastern Pennsylvania on April 25 at the VIE party venue.

Also on April 25, they will be at the International Special Events Society's ReFRESH 2013 event at Lincoln Financial Field.

On April 26, it's the closing party/cocktail reception for Philadelphia Technology Week, held at Urban Outfitters Headquarters.

And on April 28, it's the Pennsylvania Bridal Expo at the Pennsylvania Convention Center. It's all in the name of good fun, and creating memories.

"What's the first thing people want to rescue from a burning house after they are safe?" said Bender. "It's your photos. After any type of party the only thing you have is your memories and your photos."

Learn more about TapSnap by visiting http://www.TapSnap.net or calling 1-877-577-0566.

Follow us on:

Facebook: https://www.facebook.com/tapsnapshare
Twitter: https://twitter.com/tapsnapshare
YouTube: http://www.youtube.com/channel/UCIuz0-9b-5hukbALmwmYcGQ?feature=watch

About TapSnap

TapSnap is the next big innovation in event entertainment and franchising, bringing sophistication to the photo booth. Open-concept and instantly connected to social media, TapSnap blends a high-tech product with an innovative franchise model, and is based in Vancouver, Canada.

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Source: http://www.franchising.com/news/20130424_local_entrepreneur_brings_joy_of_tapsnap_phototain.html

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Facebook Messenger for Android: now with free stickers

Facebook adds a helping of cheese to Messenger with stickers

Emojis not giving that missive the right oomph? A Facebook Messenger for Android update has brought stickers into that mix with characters like cats and aliens, lending your chat head conversation just the right dose of nuance. It popped up yesterday as a hidden feature, but now you can download the final version at Google Play (at the source) -- then, just click on the smiley icon in the text input box to start dropping the cute bombs.

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Via: Phandroid

Source: Facebook (Google Play)

Source: http://feeds.engadget.com/~r/weblogsinc/engadget/~3/TXALB4MIeCA/

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Wednesday, April 24, 2013

2nd Miss. man investigated in ricin case

Federal agents wearing hazmat suits inspect the grounds around the house owned by Everett Dutschke, in connection with the recent ricin attacks, as one of his dogs howls Tuesday, April 23, 2013 in Tupelo, Miss. No charges have been filed against Dutschke and he hasn?t been arrested. (AP Photo/Rogelio V. Solis)

Federal agents wearing hazmat suits inspect the grounds around the house owned by Everett Dutschke, in connection with the recent ricin attacks, as one of his dogs howls Tuesday, April 23, 2013 in Tupelo, Miss. No charges have been filed against Dutschke and he hasn?t been arrested. (AP Photo/Rogelio V. Solis)

A federal agent wearing a hazmat suit secures a container used during a search of the Tupelo, Miss., home of Everett Dutschke, Tuesday, April 23, 2013 in connection with the recent ricin attacks. No charges have been filed against Dutschke and he hasn?t been arrested. (AP Photo/Rogelio V. Solis)

Federal authorities wear hazmat suits as they search the home of Everett Dutschke, Tuesday, April 23, 2013 in Tupelo, Miss., in connection with the recent ricin attacks. No charges have been filed against Dutschke and he hasn?t been arrested. (AP Photo/Rogelio V. Solis)

Federal agents wearing hazardous material suits and breathing apparatus inspect the home and possessions in the West Hills Subdivision house of Paul Kevin Curtis in Corinth, Miss., Friday, April 19, 2013. Curtis is in custody under the suspicion of sending letters covered in ricin to the U.S. President Barack Obama and U.S. Sen. Roger Wicker, R-Miss. (AP Photo/Rogelio V. Solis)

Paul Kevin Curtis, right, who had been in custody under the suspicion of sending letters which tested positive for ricin to U.S. President Barack Obama and U.S. Sen. Roger Wicker, R-Miss., and his brother Jack Curtis walk to a press conference in Oxford, Miss. on Tuesday, April 23, 2013. The charges were dismissed without prejudice, which means they could be re-instated if prosecutors so choose. (AP Photo/Oxford Eagle, Bruce Newman)

TUPELO, Miss. (AP) ? A second Mississippi man investigated in connection to ricin-laced letters sent to the president and a U.S. senator said Wednesday that investigators "ripped" through his house during an hours-long search the previous day after charges were dropped against another man in the case.

No investigators appeared to be at the Tupelo home Wednesday morning, and Everett Dutschke said he'd gone to a friend's house to rest. Piles of items could be seen all over the floor through the window. The home was searched Tuesday by dozens of officials, some in hazmat suits, from early in the afternoon until about 11 p.m. CDT. Officials declined to comment on what they had found or on the next phase of the investigation.

At one point, two FBI agents and two members of the state's chemical response team left Dutschke's property and began combing through ditches, culverts and woods about a block away from his house in the neighborhood of single-family detached homes.

Dutschke (DUHST'-kee), who spoke with The Associated Press by telephone during the search, said his house was also searched last week. He said he and his wife had gone to a friend's Wednesday because they didn't feel safe at their home.

"They ripped everything out of the house," he said Wednesday morning, adding: "I haven't slept at all."

No charges have been filed against Dutschke and he hasn't been arrested. Both he and Paul Kevin Curtis, who had faced charges in the case, say they have no idea how to make the poisonous ricin and had nothing to do with sending the letters to President Barack Obama, U.S. Sen. Roger Wicker of Mississippi and Mississippi county judge Sadie Holland.

Curtis, a 45-year-old celebrity impersonator, has maintained his innocence since his arrest.

Referring to investigators' questions, Curtis said after he was released from custody Tuesday afternoon, "I thought they said rice and I said, 'I don't even eat rice.' ... I respect President Obama. I love my country and would never do anything to pose a threat to him or any other U.S. official."

A one-sentence document filed by federal prosecutors said charges against Curtis were dropped, but left open the possibility they could be reinstated if authorities found more to prove their case. Prosecutors were not immediately available for comment, but the document said the ongoing investigation had revealed new information. It did not elaborate.

Dutschke and Judge Holland know each other: In 2007, he lost his Republican bid for a seat in the Mississippi House of Representatives to Holland's son, Democratic state Rep. Steve Holland, who was the incumbent.

Steve Holland previously said that during a political rally in the small town of Verona in 2007, Dutschke gave a speech disparaging the Holland family, including him, his mother and his wife.

Holland said his mother, who spoke just after Dutschke at the rally, called him back on the stage and said, "You're not going to disparage me. Now, you apologize to me."

Holland said Dutschke returned to the stage and at Judge Holland's instruction, got down on his knees and apologized, but Dutschke disputed that Tuesday.

"That's just Steve Holland being Steve Holland," he said, adding that he did not get down on his knees and apologize for anything. "He's a bit grandiose about the way he describes things."

Since Curtis' arrest at his Corinth, Miss., home on April 17, his attorneys have said their client didn't do it and suggested he was framed. An FBI agent testified in court this week that no evidence of ricin was found in searches of Curtis' home.

The dismissal is the latest twist in a case that has been strange from the beginning and rattled the country during the same week as the Boston Marathon bombing and a fertilizer plant explosion in West, Texas.

Dutschke and Curtis are no strangers to each other. Dutschke said the two had a disagreement and the last contact they had was in 2010. Dutschke said he threatened to sue Curtis for saying he was a member of Mensa, a group for people with high IQs.

Hal Neilson, an attorney for Curtis, said the defense gave authorities a list of people who may have had a reason to hurt Curtis.

"Dutschke came up," he said. "They (prosecutors) took it and ran with it. I could not tell you if he's the man or he's not the man, but there was something there they wanted to look into."

An FBI intelligence bulletin obtained by the AP said the two ricin-laced letters addressed to Obama and Wicker said: "To see a wrong and not expose it, is to become a silent partner to its continuance." Both were signed, "I am KC and I approve this message."

Curtis was already well known to Wicker because he had written to the Republican senator and other officials. Curtis also wrote a novel called "Missing Pieces," about black-market body parts he claimed to have found while working at a hospital ? a claim the hospital says is untrue. Curtis posted similar language on his Facebook page and elsewhere. The documents indicate Curtis had been distrustful of the government for years. He told the AP on Tuesday that he realizes his writings made him an easy target.

Multiple online posts under the name Kevin Curtis on various websites that could be seen by anyone refer to the conspiracy he claimed to uncover when working at a local hospital from 1998 to 2000. In one post, Curtis said he sent letters to Wicker and other politicians. He signed off: "This is Kevin Curtis & I approve this message."

Christi McCoy, another attorney for Curtis, said she doesn't know what new information prosecutors have, but said the plot to frame her client was "very, very diabolical."

Curtis, dressed after his release Tuesday in a black suit, red shirt, necktie and sunglasses, said he met Dutschke in 2005 but that for some reason Dutschke "hated" and "stalked" him. "To this day I have no clue of why he hates me."

Ricin is derived from the castor plant that makes castor oil. There is no antidote and it is at its deadliest when inhaled. It can be aerosolized, released into the air and inhaled. The Homeland Security handbook says the amount of ricin that fits on the head of a pin is enough to kill an adult if properly prepared.

Dutschke said agents asked him about Curtis, whether Dutschke would take a lie-detector test and if he had ever bought castor beans, which can be used to make the potent poison.

"I'm a patriotic American. I don't have any grudges against anybody. I did not send the letters," Dutschke said.

After charges were dropped against Curtis, he said: "I'm a little shocked."

Tuesday's events began when the third day of a preliminary and detention hearing was canceled without officials explaining the change. Within two hours, Curtis had been released.

FBI Agent Brandon Grant said in court Monday that searches last week of Curtis' vehicle and house in Corinth, found no ricin, ingredients for the poison, or devices used to make it. A search of Curtis' computers found no evidence he researched making ricin. Authorities produced no other physical evidence at the hearings tying Curtis to the letters.

All the envelopes and stamps were self-adhesive, Grant said Monday, meaning they won't yield DNA evidence. One fingerprint was found on the letter sent to a Lee County judge, but the FBI doesn't know who it belongs to, Grant said.

The experience, Curtis said, has been a nightmare for his family. He has four children ? ages, 8, 16, 18 and 20. It also has made him reflect deeply on his life.

"I've become closer to God through all this, closer with my children and I've even had some strained relationships with some family and cousins and this has brought us closer as a family," he said.

___

Wagster Pettus reported from Jackson. Associated Press writers Holbrook Mohr in Oxford, Jack Elliott in Jackson, Miss., and Pete Yost in Washington contributed to this report.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/386c25518f464186bf7a2ac026580ce7/Article_2013-04-24-Suspicious%20Letters/id-f62bb29248f44b4f976cfd7eefa343ff

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Monday, April 22, 2013

PFT: Haslam responds to allegations of wrongdoing

Jimmy HaslamGetty Images

Browns owner Jimmy Haslam apparently has received ? and is heeding ? advice from his lawyers regarding the fact that anything he says can and will be used against him, if/when he personally faces charges for fraud allegedly committed by the billion-dollar, family-owned truck-stop company he runs.

As a result, Haslam met with the media again on Monday, but instead of speaking extemporaneously and then answering questions, he read from a lengthy prepared statement that surely was written or at least reviewed and revised by one or more lawyers.

Mary Kay Cabot of the Cleveland Plain Dealer has the full text of the statement, which says nothing about the Browns.? While the smartest move at this point would be to say nothing at all about anything, Haslam realizes that his customers could scatter and his employees could flee and the entire operation could disintegrate without real efforts to hold the business together.

But in starting the process of rebuilding trust and restoring confidence, Haslam comes dangerously close to admitting that improprieties occurred.? For example, in explaining that the company will now have a ?Chief Compliance Officer,? Haslam basically acknowledges that, if whoever blew the whistle to the feds had a way to blow the whistle internally, the whole thing could have been fixed without outside scrutiny.

?The establishment of a position of Chief Compliance Officer is important, because had we had one before, perhaps some team member would have raised a question about manual rebates internally before anyone would ever have gone to federal investigators,? Haslam said.

Haslam also continues to emphasize that the situation affects only a ?narrow? portion of the company?s business.? But with 3,300 trucking-company customers, a lot of fraud can still happen to a ?narrow? band of customers.? Reciting instances of compliance with the lawyer is never a defense to the specific instances when the law was broken.

Most significantly, Haslam explained that the company placed on ?administrative leave several members of our diesel fuel team.?? Presumably, that includes V.P. of sales John Freeman, whose colorful and profane terms were caught on tape by an informant, along with an admission that Haslam was aware of the alleged rebate scam.

If/when Freeman agrees to testify against Haslam, Haslam will have a serious problem; in the interim, Haslam and his lawyers necessarily must commence preparations for painting this once-trusted employee as inherently unreliable, especially as to anything he would say under oath about Haslam.

Of course, none of it matters if Pilot Flying J ends up being driven into the ground by the loss of customers and personnel.? Haslam?s statement from Monday is aimed at keeping that from happening.

Source: http://profootballtalk.nbcsports.com/2013/04/22/haslam-reads-lengthy-statement-to-media-takes-no-question/related/

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Saturday, April 20, 2013

Wall Street gets Google lift in S&P's worst week since November

By Caroline Valetkevitch

NEW YORK (Reuters) - Stocks rose on Friday as earnings from Google and other companies lifted tech shares, but the gains weren't enough to stop the S&P 500 from suffering its worst week since November.

High volatility marked the week, with the S&P 500 falling 2.3 percent on Monday in its worst day since November 7, which fueled talk that the market's long-awaited pullback had arrived.

Friday's trading volume, at 6.4 billion, was the lowest of the week, but in line with the average for the year. Much of Boston, a major U.S. financial center and home to a number of the country's biggest mutual fund companies, was under virtual lockdown as police killed one suspect in the Boston Marathon bombing in a shootout and mounted house-to-house searches for a second man.

For the week, the S&P 500 ended down 2.1 percent but the index managed a finish above its 50-day moving average after ending below that level on Thursday for the first time this year.

Boosting the S&P 500 on Friday were shares of Google, which gained 4.4 percent to $799.87 a day after posting upbeat results. At least six brokerage firms have raised their target on Google's stock price.

The Dow finished barely in positive territory, held back by shares of International Business Machines , which posted their largest drop in eight years after the company's quarterly results missed estimates. IBM's stock ended down 8.3 percent at $190.

"Unless there's a shock to the system, investors will move back into the market as we head through earnings season, but now investors have an opportunity to study the winners and losers more closely," said Michael Sheldon, chief market strategist at RDM Financial in Westport, Connecticut.

The Dow Jones industrial average <.dji> rose 10.37 points, or 0.07 percent, to 14,547.51 at the close. The Standard & Poor's 500 Index <.spx> gained 13.64 points, or 0.88 percent, to finish at 1,555.25. The Nasdaq Composite Index <.ixic> rose 39.69 points, or 1.25 percent, to close at 3,206.06.

For the week, the Dow slid 2.1 percent, while the Nasdaq lost 2.7 percent. Markets were roiled earlier in the week by the plunge in gold prices and slower growth out of China, the world's second-largest economy.

Still, the S&P 500 remains up about 9 percent for the year, and analysts said the pullback could give investors a chance to reevaluate their bets.

Options volume began the day unusually light for expiration day, which is typically a heavily traded session, as traders focused on developments in Boston. But trading in options picked up as the day progressed and ended near average levels.

The Boston situation "does disrupt activity. If you're a financial adviser, you're probably not having meetings today. But in terms of a corporate entity, most of the big ones in the city are probably operating pretty normally," said John Canally, investment strategist and economist at the Boston office of LPL Financial, which is the nation's largest independent broker-dealer.

On last month's expiration day, overall volume spiked to 8.6 billion shares traded, the busiest day of the year so far, but expiry days in January and February had volume of just 6.7 billion to 6.8 billion shares.

Among other tech gainers, shares of Microsoft jumped 3.4 percent to $29.77 and topped the Nasdaq's most-active list after the company reported quarterly revenue and earnings that exceeded Wall Street's expectations.

Shares of Boeing Co gained 2.1 percent to $87.96 after U.S. regulators approved a revamped battery system for its 787 Dreamliner. The jet was grounded in January because the plane's lithium-ion batteries overheated.

Less-than-stellar earnings from McDonald's and General Electric also weighed on the blue chips.

GE shares fell 4.1 percent to $21.75 after the conglomerate reported a quarterly profit in line with expectations as GE sold more jet engines and shed its stake in NBC Universal. The stock topped the New York Stock Exchange's list of most actively traded names.

McDonald's stock lost 2 percent to $99.92 after the world's biggest fast-food chain reported a first-quarter profit that fell short of Wall Street's expectations and said sales at established U.S. restaurants fell 1.2 percent.

Friday's volume totaled 6.4 billion shares traded on the New York Stock Exchange, the Nasdaq and the NYSE MKT, in line with the average daily closing volume of 6.4 billion this year.

Advancers outnumbered decliners on the New York Stock Exchange by a ratio of about 11 to 4, while on the Nasdaq, nearly 17 stocks rose for every eight that fell.

(Additional reporting by Leah Schnurr, Angela Moon and Doris Frankel; Editing by Jan Paschal)

Source: http://news.yahoo.com/stock-futures-signal-gains-ge-eyed-091437318--finance.html

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Blackstone drops out of race to buy Dell

Dell says buyout specialist Blackstone Group is ending a bid to buy the slumping computer maker, less than a month after pitching a plan to trump an offer from the company's CEO and founder.

A letter to Dell Inc. from Blackstone and others involved in the bid says a steep slump in PC shipments and Dell's eroding financial profile prompted them to end their bid. The letter notes that PC shipments plunged by 14 percent in the first quarter, and Dell has lowered its operating income forecast since the bid was submitted.

The Round Rock, Texas, company agreed earlier this year to sell itself to CEO Michael Dell and a group of investors led by Silver Lake Partners for $24.4 billion, or $13.65 per share. But key shareholders have been unhappy about that offer.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/f70471f764144b2fab526d39972d37b3/Article_2013-04-19-Dell%20Acquisition/id-af4dafc5cd4a4c2d8ac13fa08aa1d54e

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Monday, April 15, 2013

Brain development is guided by junk DNA that isn't really junk

Apr. 15, 2013 ? Specific DNA once dismissed as junk plays an important role in brain development and might be involved in several devastating neurological diseases, UC San Francisco scientists have found.

Their discovery in mice is likely to further fuel a recent scramble by researchers to identify roles for long-neglected bits of DNA within the genomes of mice and humans alike.

While researchers have been busy exploring the roles of proteins encoded by the genes identified in various genome projects, most DNA is not in genes. This so-called junk DNA has largely been pushed aside and neglected in the wake of genomic gene discoveries, the UCSF scientists said.

In their own research, the UCSF team studies molecules called long noncoding RNA (lncRNA, often pronounced as "link" RNA), which are made from DNA templates in the same way as RNA from genes.

"The function of these mysterious RNA molecules in the brain is only beginning to be discovered," said Daniel Lim, assistant professor of neurological surgery, a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, and the senior author of the study, published online April 11 in the journal Cell Stem Cell.

Alexander Ramos, a student enrolled in the MD/PhD program at UCSF and first author of the study, conducted extensive computational analysis to establish guilt by association, linking lncRNAs within cells to the activation of genes.

Ramos looked specifically at patterns associated with particular developmental pathways or with the progression of certain diseases. He found an association between a set of 88 long noncoding RNAs and Huntington's disease, a deadly neurodegenerative disorder. He also found weaker associations between specific groups of long noncoding RNAs and Alzheimer's disease, convulsive seizures, major depressive disorder and various cancers.

"Alex was the team member who developed this new research direction, did most of the experiments, and connected results to the lab's ongoing work," Lim said. The study was mostly funded through Lim's grant - a National Institutes of Health (NIH) Director's New Innovator Award, a competitive award for innovative projects that have the potential for unusually high impact.

Unlike messenger RNA, which is transcribed from the DNA in genes and guides the production of proteins, lncRNA molecules do not carry the blueprints for proteins. Because of this fact, they were long thought to not influence a cell's fate or actions.

Nonetheless, lncRNAs also are transcribed from DNA in the same way as messenger RNA, and they, too, consist of unique sequences of nucleic acid building blocks.

Evidence indicates that lncRNAs can tether structural proteins to the DNA-containing chromosomes, and in so doing indirectly affect gene activation and cellular physiology without altering the genetic code. In other words, within the cell, lncRNA molecules act "epigenetically" -- beyond genes -- not through changes in DNA.

The brain cells that the scientists focused on the most give rise to various cell types of the central nervous system. They are found in a region of the brain called the subventricular zone, which directly overlies the striatum. This is the part of the brain where neurons are destroyed in Huntington's disease, a condition triggered by a single genetic defect.

Ramos combined several advanced techniques for sequencing and analyzing DNA and RNA to identify where certain chemical changes happen to the chromosomes, and to identify lncRNAs on specific cell types found within the central nervous system. The research revealed roughly 2,000 such molecules that had not previously been described, out of about 9,000 thought to exist in mammals ranging from mice to humans.

In fact, the researchers generated far too much data to explore on their own. The UCSF scientists created a website through which their data can be used by others who want to study the role of lncRNAs in development and disease.

"There's enough here for several labs to work on," said Ramos, who has training grants from the California Institute for Regenerative Medicine (CIRM) and the NIH.

"It should be of interest to scientists who study long noncoding RNA, the generation of new nerve cells in the adult brain, neural stem cells and brain development, and embryonic stem cells," he said.

Other co-authors who worked on the study include UCSF postdoctoral fellows Aaron Diaz, PhD, Abhinav Nellore, PhD, Michael Oldham, PhD, Jun Song, PhD, Ki-Youb Park, PhD, and Gabriel Gonzales-Roybal, PhD; and MD/PhD student Ryan Delgado. Additional funders of the study included the Sontag Foundation and the Sandler Foundation.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

###

Follow UCSF UCSF.edu | Facebook.com/ucsf | Twitter.com/ucsf | YouTube.com/ucsf

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The above story is reprinted from materials provided by University of California, San Francisco (UCSF).

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


Journal Reference:

  1. Alexander D. Ramos, Aaron Diaz, Abhinav Nellore, Ryan N. Delgado, Ki-Youb Park, Gabriel Gonzales-Roybal, Michael C. Oldham, Jun S. Song, Daniel A. Lim. Integration of Genome-wide Approaches Identifies lncRNAs of Adult Neural Stem Cells and Their Progeny In Vivo. Cell Stem Cell, 2013 DOI: 10.1016/j.stem.2013.03.003

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_science/~3/Lj8DVrDLFOg/130415172010.htm

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Thursday, April 11, 2013

Giffords vows to be 'tougher' (CNN)

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, News Feeds and News via Feedzilla.

Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/297882781?client_source=feed&format=rss

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10 fun facts about Money in the Bank contracts

All WWE programming, talent names, images, likenesses, slogans, wrestling moves, trademarks, logos and copyrights are the exclusive property of WWE, Inc. and its subsidiaries. All other trademarks, logos and copyrights are the property of their respective owners. ? 2013 WWE, Inc. All Rights Reserved. This website is based in the United States. By submitting personal information to this website you consent to your information being maintained in the U.S., subject to applicable U.S. laws. U.S. law may be different than the law of your home country. WrestleMania XXIX (NY/NJ) logo TM & ? 2013 WWE. All Rights Reserved. The Empire State Building design is a registered trademark and used with permission by ESBC.

Source: http://www.wwe.com/inside/money-in-the-bank-ladder-match-contract-fun-facts

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Jurassic Park's Dinosaur Sound Effects Were Actually Animal Sex Sounds

So, uh, this is an uncomfortable one. You know the dinosaur sounds from Jurassic Park that framed the way you imagined every dinosaur ever? They were actually recordings of animals boning, or just about to bone. More »
    


Source: http://feeds.gawker.com/~r/gizmodo/full/~3/JBSniEA6QlM/jurassic-parks-dinosaur-sound-effects-were-actually-animal-sex-sounds

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Philadelphia Orchestra announces China tour

PHILADELPHIA (AP) ? Forty years after it became the first U.S. orchestra to visit China, the Philadelphia Orchestra is planning to go back with a new tour and new program.

The orchestra on Wednesday announced plans for a summer tour and outreach program that will visit Hangzhou, Shanghai, Tianjin, Beijing and Macao between May 29 and June 10.

In addition to performances the orchestra plans a grassroots exchange with young Chinese musicians.

Donald Runnicles will conduct seven performances during the tour. Under legendary conductor Eugene Ormandy the orchestra visited China in 1973 as part of a historic thaw in relations between the two countries.

To celebrate the 40th anniversary musicians from the China National Symphony Orchestra and musicians from The Philadelphia Orchestra will come together for a celebratory performance at the National Center for the Performing Arts in Beijing on June 6.

The Philadelphia Orchestra said it "looks toward a rich future in China" defined by a commitment to serving as a cultural ambassador for the United States.

The tour is part of a rebuilding project that began after the orchestra stunned music lovers in 2011 by becoming the first major U.S. orchestra to seek Chapter 11 bankruptcy reorganization. The world-renowned 112-year-old orchestra had struggled with dwindling attendance and donations, shrinking endowment income, the recession and an aging audience.

The orchestra emerged from bankruptcy last year.

Source: http://news.yahoo.com/philadelphia-orchestra-announces-china-tour-070200497.html

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Wednesday, April 10, 2013

The 5 greatest shots at the Masters

FILE - In this April 13, 1986, file photo, Jack Nicklaus watches his putt drop for a birdie on the 17th hole at Augusta National during the Masters golf tournament in Augusta, Ga. Nicklaus went on to win his sixth Masters title. Nicklaus loves absolutely everything about Augusta. Nicklaus sat in the interview room at the Masters for an hour Tuesday, April 9, 2013, and had more than enough material for two. (AP Photo/Phil Sandlin, File)

FILE - In this April 13, 1986, file photo, Jack Nicklaus watches his putt drop for a birdie on the 17th hole at Augusta National during the Masters golf tournament in Augusta, Ga. Nicklaus went on to win his sixth Masters title. Nicklaus loves absolutely everything about Augusta. Nicklaus sat in the interview room at the Masters for an hour Tuesday, April 9, 2013, and had more than enough material for two. (AP Photo/Phil Sandlin, File)

Tiger Woods tees off on the first hole during a practice round for the Masters golf tournament Tuesday, April 9, 2013, in Augusta, Ga. (AP Photo/Charlie Riedel)

Bubba Watson points to the tee from the first fairway during a practice round for the Masters golf tournament Tuesday, April 9, 2013, in Augusta, Ga. (AP Photo/Darron Cummings)

(AP) ? No other major championship has a greater collection of signature shots than the Masters, mainly because it's the only major held on the same course. And it helps that Augusta National is such a course that allows for such big moments.

There was the "shot heard 'round the world" and a shot right out of "Bubba golf." There has been an eagle made on every hole except for the par 5s, where there has been an albatross on all of those, with Louis Oosthuizen finally get a "2'' on the par-5 second hole last year.

According to an Associated Press story from 1935, there were only about 2,000 people in the gallery when Gene Sarazen holed out his 4-wood on the par-5 15th hole in 1935. Thousands more later claimed to witness the historic shot.

Here's one list of the five greatest shots in Masters history:

___

5. JACK NICKLAUS IN 1986

No list of great shots at Augusta National should exclude Jack Nicklaus, a six-time champion. His 30 on the back nine in 1986, which carried him to his sixth green jacket, was the most famous charge of all. If there was a signature moment, it happened on the par-3 16th.

Nicklaus was coming off an eagle when he walked over to the 16th tee, which was playing about 175 yards. He hit a 5-iron, and as the ball was still climbing, Nicklaus stooped over and picked up the tee ? partly because he couldn't see so well, partly because he knew he hit it how he wanted.

His son, Jackie, was caddying for him that week and said, "Be right."

Nicklaus replied, "It is."

And it was.

The ball landed right of the pin and trickled down, narrowly missing a hole-in-one and leaving him a short birdie putt that he converted on his way to victory.

___

4. SANDY LYLE IN 1988

Sandy Lyle had the lead going into the final round of the 1988 Masters, but found himself in a tight battle with Mark Calcavecchia on the back nine. He was tied for the lead going to the last hole, knowing he would need a birdie to win.

Hitting a 1-iron into the first of two bunkers down the left side of the fairway was probably not the best way to make birdie.

That's when Lyle delivered one of the greatest shots on the closing hole at Augusta. He hit a 7-iron just over the tall lip of the bunker, and the shot covered the flag and landed beyond the pin, rolling back to 10 feet.

Lyle made the birdie putt to become the first British player in a green jacket.

___

3. TIGER WOODS IN 2005

Tiger Woods found himself in a surprising duel along the back nine in 2005 with Chris DiMarco. Woods had a one-shot lead with three holes to play, and he looked to be in trouble when he went long on the par-3 16th hole, and DiMarco had a 15-foot birdie putt.

The pin was in its traditional Sunday position, and Woods was in the wrong spot. He had to play the chip away from the flag and catch the slope just right, hopefully without too much speed that it would run by the hole and leave himself a tough putt for par. After measuring the shot for the longest time, he sent his pitch up the slope, and it slowly made a U-turn toward the hole.

The ball broke gently to the left and looked like it might go in, except that it was slowing to a stop. One last turn moved it an inch from the hole. Another turn left it on the on the edge of the cup. And after 2 full seconds, gravity took over and the ball disappeared for birdie.

Despite such a dramatic moment for a two-shot lead, Woods bogeyed the next two holes and had to make one last birdie in a playoff to win.

___

2. BUBBA WATSON IN 2012

The final round of the 2012 Masters produced the rarest shot in golf when Louis Oosthuizen holed out a 4-iron on the par-5 second hole for an albatross. At the end of the day, Bubba Watson hit a shot that was rare in its own right. It was a shot only Bubba could hit.

Watson and Oosthuizen headed to the 10th hole for the second playoff hole, and Watson was in trouble. He hit driver deep into the woods to the right of the fairway. Watson hung his head for a moment, figuring he would have to scramble for any chance of par. He always tells his caddie, "If I have a swing, I have a shot."

No one could have drawn this one up. He hit a 40-yard hook with a sand wedge, low to get under the trees, then rising to get onto the elevated green. The ball somehow landed on the green with enough side spin to turn up the hill and settle about 10 feet away. Two putts later, Watson had his par ? and a green jacket.

___

1. GENE SARAZEN IN 1935

Gene Sarazen was about the only player who didn't think the second edition of the Masters was over. Craig Wood was in the clubhouse at 6-under 282. Sarazen was in the fairway on the par-5 15th hole, three shots behind while playing with Walter Hagen.

Sarazen had a 4-wood that he called his "Dodo" club, and while he didn't have a great lie, thought he should go for the green from 235 yards away. He tried to play it slightly off the toe to get a little extra distance, and the shot came off perfectly.

The ball bounced just short of the green, hopped on and rolled into the cup for an albatross. Sarazen closed with three pars to force a playoff, and he beat Wood over 36 holes the next day.

It remains the most important shot in tournament history because it put the Masters on the map.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/347875155d53465d95cec892aeb06419/Article_2013-04-10-GLF-Masters-Five-Greatest-Hits/id-5a5916909f9e46ab9724f2611f9adcef

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New Jersey four year-old shoots playmate in apparent accident

By Atossa Araxia Abrahamian

(Reuters) - A 4-year-old New Jersey boy shot and killed a 6-year-old playmate with a rifle he found in his family's home, police said on Tuesday.

The shooting in Toms River, New Jersey, on Monday, came two days after another 4-year-old shot and killed the wife of a sheriff's deputy at her home in Lebanon, Tennessee, using a handgun he found on a bed.

Both shootings were under investigation but believed to be accidental, authorities said.

Toms River Police Chief Michael Mastronardy said the children were playing with a golf cart outside the 4-year-old's home when the younger boy went inside and got a .22-caliber rifle.

The boy then either pulled the trigger or discharged the gun by accident, striking his friend in the head.

The 4-year-old's mother called 911 and the older boy was rushed to Jersey Shore Medical Center in Neptune, New Jersey, where he died at 5 p.m. on Tuesday, Mastronardy said.

The victim was identified as Brandon Holt of Toms River, police said.

Mastronardy would not comment on whether the weapon belonged to a licensed gun owner, saying the matter was under investigation. He urged gun owners to secure their weapons.

He said it would be up to Ocean County, New Jersey prosecutors to decide whether charges would be filed in the case.

President Barack Obama has been pressing Congress to pass stricter gun control laws after the elementary school shooting in Newtown, Connecticut, that left 20 children and six adults dead.

(Additional reporting by Ellen Wulfhorst; Editing by Barbara Goldberg, Bill Trott and Doina Chiacu)

Source: http://news.yahoo.com/jersey-4-old-shoots-playmate-apparent-accident-005745330.html

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Mad Men, Season 6

My vote for best updated 'do goes to Harry Crane, with his half-hearted mop and those burgeoning burns. But?furthering our semiotics-of-hair discussion, and regarding Betty?s newly ravened tresses?Hanna, I want to defend Henry Francis against your casual dismissals. Am I forgetting some major recent sin on his part? I feel like he might be the kindest, most morally centered, most mentally stable character on the show. And yet when he thoughtfully comforts Betty, you sniff at his ?pallid compliments.?

What?s the poor guy gotta do? I acknowledge he could sprinkle a little more mischief into his mindset. But is it the nature of TV viewership, or simply human nature, that spurs us to root for Don?s putrid behavior while we find fault with Henry?s unimpeachable steadiness?

On the other hand, I?m all for hating on kiss-up Bob, the guy who doles out hot coffees to every higher-level executive he passes. We spent a lot of time with him this episode, without really understanding why. I?m keen to discover what sort of role he?ll play this season.

With all that talk about doorways, and Betty finding new paths: Did you notice that she shredded the shoulder of her coat as she stepped through that door on St. Marks Place? Has the experience torn an irreparable hole in her soul? Is she in for a little more wear and tear as she navigates the changing times?

Also, while Hanna and I loved Peggy?s executive mastery, our editor Dan Kois just sent me an email arguing that Peggy?s not really forging a new path at all?she?s becoming Don. Commenter ?Larry? similarly noted, ?You can hear Don perfectly clearly in Peggy's work voice. The scene was more to show how Don formed Peggy than to simply show that she was an adult amongst kids.? I?d add that Peggy?s creative breakthrough happened in one of those ?cracks? you mentioned, Hanna. It wasn?t scotch and soda, but rather meatball subs and music, that led to her eureka.

Maybe Don?s Hawaii pitch was genius and the clients just didn?t get it. But Don once possessed a Steve Jobs-like reality distortion field that compelled everybody within a conference table?s radius to lap up every word he said. It seems that power may have faded a bit.

I?m fading a bit, too. Time to replenish in preparation for next week?s episode.

Source: http://feeds.slate.com/click.phdo?i=b1274175ce33b16f83a6ad5e45a05387

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AT&amp;T launching LTE in Paris and Manhattan this summer (Texas and Kansas, that is)

Manhattan and Paris Kansas and Texas, that is are among next 16 AT&T LTE cities

AT&T has announced that it'll fire up LTE coverage in 16 new cities this this summer and that it has expanded or turned on the signal in four other centers. Residents of Kalamazoo, MI and Wilson, NC will now see the much sought-after 4G symbol, while previously neglected Bay Area centers like San Rafael and Brentwood, along with parts of Greensboro, NC also have coverage. Meanwhile, the famously-named centers mentioned earlier will get 4G later this summer, along with other notables like Rio Grande Valley, TX, Columbus, IN and yes, Athens TX. It makes us wonder if Ma Bell's getting a little playful with its rollout decisions -- check the PR after the break for more info.

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Source: http://www.engadget.com/2013/04/10/manhattan-and-paris-among-ATT-LTE-4G/

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Research advances therapy to protect against dengue virus

Apr. 8, 2013 ? Nearly half of the world's population is at risk of infection by the dengue virus, yet there is no specific treatment for the disease. Now a therapy to protect people from the virus could finally be a step closer, thanks to a team at MIT.

In a paper published today in the Proceedings of the National Academy of Sciences, the researchers, from MIT's Koch Institute of Integrative Cancer Research, present a novel approach to developing a dengue therapy using mutated antibodies.

According to a study by the International Research Consortium on Dengue Risk Assessment, Management and Surveillance, up to 390 million people are infected with the dengue virus each year. For most people the mosquito-borne virus causes flulike symptoms, including fever, headache and joint pain. But for some, particularly children, the virus can develop into the far more serious dengue hemorrhagic fever, causing severe blood loss and even death.

Despite the threat posed by the disease, developing a vaccine against dengue has so far proved challenging, according to Ram Sasisekharan, the Alfred H. Caspary Professor of Biological Engineering at MIT. That's because dengue is not one virus but four different viruses, or serotypes, each of which must be neutralized by the vaccine.

Protecting people from only one or some of the four viruses could cause them to develop the more severe form of dengue if they later become infected with one of the other serotypes, in a process known as antibody-dependent enhancement, Sasisekharan says. "That was the motivation for carrying out our study, to generate a fully neutralizing antibody that works for all four serotypes."

Pushing the envelope

Efforts to develop a therapeutic antibody for dengue are focused on a part of the virus called the envelope protein. "This is a very critical protein that allows the virus to latch on to the appropriate receptor within the host, to infect them, replicate and spread," Sasisekharan says.

The envelope protein contains two regions of interest, known as the loop and the "A" strand. Research teams have previously attempted to engineer an antibody that targets the loop region of the virus protein, as this is known to be able to attack all four serotypes if targeted in the right way.

However, the antibodies that target the loop region tend to have low potency, meaning they are unable to completely neutralize the virus. This increases the risk of more severe secondary dengue infection.

So a team led by Sasisekharan decided instead to look for antibodies that target the "A" strand region of the protein. Such antibodies tend to have much higher potency, but they are unable to neutralize all four serotypes.

450-fold increase

The researchers chose as their model an antibody known as 4E11, which has been shown in tests to neutralize dengue 1, 2 and 3, but not dengue 4. "We wanted to see if we could get good neutralizing activity to dengue 4, and also tweak the antibody to increase the potency associated with the other subtypes," Sasisekharan says.

The authors mined existing antibody-antigen complexes to analyze the physical and chemical features that play an important role in their interaction, such as hydrogen bonding and ionic attraction. Taking a statistical approach, they then ranked these features in terms of their importance to each of the antibody-antigen interactions.

This significantly narrowed the number of possible changes, or mutations, the researchers needed to make antibody 4E11 in order to improve its ability to neutralize all four viruses, in particular dengue 4. "So rather than random screening, we used a statistically driven approach so we knew the regions to focus on, and what things we had to change," Sasisekharan says.

As a result, the researchers came up with 87 possible mutations, which they were able to reduce to just 10 changes after further investigation.

When they tested their mutated antibody on samples of the four dengue serotypes in the laboratory, they found it had a 450-fold increase in binding to dengue 4, a 20-fold increase in binding for dengue 2, and lesser improvements in binding for dengue 1 and 3, Sasisekharan says.

The researchers have developed a novel computational method for predicting protein-protein interaction that captures the essential chemical and physical features of interacting surfaces, says Subhash Vasudevan, an associate professor in the Emerging Infectious Diseases Program at the Duke-NUS Graduate Medical School in Singapore.

"By learning and validating data from numerous three-dimensional structures of interacting antibody and protein complexes, the researchers gained valuable insights that enabled them to redesign a dengue virus envelope antibody to improve its binding by an astounding 450-fold," Vasudevan says.

"The cross-reactive and pan-dengue neutralizing antibody was protective against all four serotypes in cell culture and in an animal model of infection," he adds.

The MIT researchers are now preparing for potential preclinical trials, and hope to be ready to test the antibody on humans within the next two to three years. In the meantime, they are also investigating other targets for their immunotherapy approach, including the influenza virus.

This work was funded by the National Institutes of Health and the National Research Foundation Singapore through the Singapore-MIT Alliance for Research and Technology's Infectious Diseases Research Program.

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Story Source:

The above story is reprinted from materials provided by Massachusetts Institute of Technology. The original article was written by Helen Knight.

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


Journal Reference:

  1. K. Tharakaraman, L. N. Robinson, A. Hatas, Y.-L. Chen, L. Siyue, S. Raguram, V. Sasisekharan, G. N. Wogan, R. Sasisekharan. Redesign of a cross-reactive antibody to dengue virus with broad-spectrum activity and increased in vivo potency. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1303645110

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/~3/Oe275WFS7dM/130408184642.htm

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