Tuesday, July 30, 2013

Indonesia promises not to snoop on foreign leaders: media

JAKARTA (Reuters) - Indonesia pledged not to eavesdrop on foreign leaders when it hosts a major summit later this year despite irritation over reports that its own leader was spied on when he was overseas.

Classified documents leaked last month by whistleblower Edward Snowden showed British intelligence services had used "groundbreaking intelligence capabilities" to monitor the communications of visiting world leaders at the G-20 summit in 2009, according to The Guardian daily. Indonesian President Susilo Bambang Yudhoyono attended that gathering.

The Sydney Morning Herald reported last week that the Australian government was among those which made use of the British intelligence on Yudhoyono and other Asian leaders.

"We must give a guarantee that such practices will not happen here in Indonesia, especially during the (upcoming) APEC summit in Bali," Marciano Norman, head of the state intelligence agency, was quoted as saying on Tuesday by the Jakarta Post daily.

The Asia-Pacific Economic Cooperation (APEC) has 21 members including the United States, China and Russia. Britain is not a member.

"Indonesia has never had a practice of spying on visiting foreign delegates. If there's any truth to the news reports, then what the UK did is for sure completely unethical," Teuku Faizasyah, presidential spokesperson for foreign affairs, told Reuters.

"You're hosting foreign dignitaries and there should be some respect for their privacy."

(Reporting by Kanupriya Kapoor, editing by Jonathan Thatcher and Ron Popeski)

Source: http://news.yahoo.com/indonesia-promises-not-snoop-foreign-leaders-media-094820500.html

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Wiebe beats Langer to win Senior British Open

SOUTHPORT, England (AP) ? Bernhard Langer gave Mark Wiebe one too many chances at the Senior British Open.

Wiebe took advantage of Langer's failure to close out the tournament, beating the German on the fifth playoff hole Monday at Royal Birkdale for his first senior major title.

The American used a superb approach shot from the rough to set up a two-putt for par, while Langer failed to get up and down, seeing his par putt stay out.

"I'm speechless," Wiebe said. "I think it's always better for both players had there been a birdie to win the playoff instead of a bogey, but right now, I don't really care. I'm glad it's over, and I'm honored.

Langer led by two shots going into the final hole of regulation Sunday, only to settle for a double bogey when he struggled to get out of a bunker. The playoff was then halted after two holes because of darkness and resumed Monday, with Langer immediately missing another chance to win when his 12-foot putt wouldn't drop.

"I just was luckier today and last night than Bernie I guess," Wiebe said. "I also feel like Bernie has won, what, a couple hundred tournaments. He's won so many, I feel like this was my turn."

Langer, who won the tournament in 2010, was up by three shots entering the fourth round. He looked certain to earn a second Senior British Open title when he teed off at the 72nd.

But his approach shot landed in a greenside bunker, and he needed two strokes just to get out of the sand. Wiebe, meanwhile, shot a 4-under 66 to match the German at 9-under 271.

"Obviously, not what I wanted. But the major mistake was again yesterday, the 72nd hole," Langer said. "In the playoff anybody can win. It comes down to one good shot or one bad shot. And that's what happened. Mark is a very deserving champion."

This was the first time in the 27-year history of the Senior British Open the tournament finished on a Monday.

Former U.S. Ryder Cup captain Corey Pavin shared third ? three shots back ? with David Frost of South Africa and Peter Senior of Australia. It was the third year in a row Pavin tied for third at the tournament.

Wiebe's season has been plagued by a back and arm injury and he hasn't finished in the top 10 on the U.S. Champions Tour all year. But he said he could swing a club without pain again, which "helped me so much with my attitude."

"Once I realized I could play and it didn't hurt very much to swing," Wiebe said, "I was instantly in a great mood, and I knew I was playing good."

Source: http://news.yahoo.com/wiebe-beats-langer-win-senior-british-open-084911167.html

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FSU football: Across enemy lines

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Source: http://www.tallahassee.com/article/20130728/FSU03/307280036/1103/RSS18

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Savvy Secrets For Traveling On A Budget | Content for Reprint

Author: Tony Shawrtz | Total views: 60 Comments: 0
Word Count: 787 Date:

Traveling is fun, even if it's just for business. One thing which can take some of the joy out of traveling is spending a lot of cash to do it. In this article, we will share strategies to get you to your desired location without spending too much cash.

If you are traveling with your child, carry a photo of your child just in case he or she gets lost. Losing track of a child can be very frightening. However, in case it happens, you should be prepared. If you have a picture of your child on hand, it can really help to locate him or her in a crowd more quickly.

If you have known food allergies, be very careful about food when traveling in foreign countries. You need to know the language's food related words, particularly if you have bad reactions to foods. This will enable you to tell your staff about your allergies and in times of emergency, you will be able to tell medical professionals about your condition.

Try to purchase tickets to amusement parks in advance so that you could print them out. Although you may pay a service fee for this option, it is worth it to bypass long lines for entrance to the park. If the park you are visiting has a timed entry, you can skip admission lines too.

Make sure to get to the port city the night before your cruise to avoid the chance of missing it. Ask the hotel's staff when it comes to parking deals even though none are published.

Many stores charge too much for these types of products. Try to save space in other ways, like packing more efficiently or eliminating unnecessary items. You can have more space in your bags than you thought if you pack properly.

Deserts offer remarkable and memorable vistas and exotic plant and animal life. Everyone should experience the majesty and austerity of the desert at some point in their life.

Making your travel arrangements online is now easier than ever before. Travel sites will help you plan your travel itinerary with minimal effort. Booking flights, hotels or rental cars can all be done on the Internet. Many of these sites offer package deals that can save you a lot of money. Travel websites also offer good deals in planning your trip, as well as discounts on last minute travel.

Make sure you get the latest e-newsletters of the airlines you use. Their online newsletters often include last-minute discounts, special offers and other promotions not offered to any other consumers. Yes, they will fill your inbox more, but the rewards and savings can be worth it.

Traveling to far away places is not the only way to have a wonderful quick get-away or enjoyable day trip. You may enjoy yourself right around your home or in a neighboring state. You can significantly reduce travel expenses and support local businesses by remaining close to home. You may be surprised to find a real gem, hiding in your own "backyard".

Road trips can be fun if you bring along a few of your favorite tunes. Often your radio signal will die as you drive from town to town, but you can avoid that by having your own music with you.

Staying awake until about 8pm in local time will help you to adjust better in the new time zone. If you go to bed early, even if you're tired, it can make your jet lag stay longer because you keep your body in sync with the time zone from home. Getting over jet lag quicker will give you more time to enjoy your vacation.

Take some bottled water along on your journey if you are traveling abroad. Drinking water in most other countries hasn't been purified and may cause a range of different illnesses. Use bottled water when you brush your teeth. This is one subtle way that tap water can make you sick.

If the site you are using offers an online tracking feature, use it. They will give you the most up-to-date information on travel fees. Email alerts will be sent to you if there is a lower price available on the flight you are monitoring or have booked.

As stated initially in this guide, travel is fun although planning for a trip may not be. There are certain ways to help make planning a trip easier, creating a more successful journey. Keep this advice in mind to make sure that your trip will stay on track.

If your kids want to travel to Disney and you are on a tight budget, then you better know how to save when you travel there. You should know about insider secrets and here's one of the guides you should take disney world insider review

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1: Turn This Year's Renter Into An Annual Vacation Rental Guest

In the business world, success depends on repeat customers and their referrals - the vacation home rental business is no exception. Which is why it is startling to note that repeat renters in this business account for only 10% of all bookings.

2: Palace On Wheels And Other Heritage Trains In India - Combining Extravagance With Holidays

If you want to discover India, the most convenient and pleasant way is to travel by one of the several luxurious trains of the Indian Railways.

3: The Latest News On Tibet Travel Permit 2013

Tibet Permits are issued to solo travelers in 2013. The regulation that a group must have two or five with the same nationality has been CANCLLED.

4: 5 Top Snow Boarding Destinations

Now let me tell you about some of the greatest places that there are to snow board in the world. I really mean I am going to tell you about the places, that if you are a snow boarder you simply must visit if you want to have experienced the greatest snow boarding that is out there.

5: Cirrus SR22: A Magnificent Demo Flight

Wow Recently I enjoyed what has to be considered a "milestone day" in the life of an aviator, as myself and one of my best buds in Eugene got to go flying

Source: http://www.content4reprint.com/recreation-and-leisure/travel/savvy-secrets-for-traveling-on-a-budget.htm

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Friday, June 28, 2013

Texas state senator Wendy Davis filibusters her way to Democratic stardom (Washington Post)

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 Feeds and Widgets via Feedzilla.

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Michelle Obama Joins Instagram, Posts Photo From Africa

Source: http://www.thehollywoodgossip.com/2013/06/michelle-obama-joins-instagram-posts-photo-from-africa/

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The Daily Roundup for 06.27.2013

You might say the day is never really done in consumer technology news. Your workday, however, hopefully draws to a close at some point. This is the Daily Roundup on Engadget, a quick peek back at the top headlines for the past 24 hours -- all handpicked by the editors here at the site. Click on through the break, and enjoy.

DNP The Daily RoundUp

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Source: http://feeds.engadget.com/~r/weblogsinc/engadget/~3/Lw4GPTqNFXQ/

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Thursday, June 20, 2013

Oil falls most since November on Fed comments

NEW YORK (AP) ? Oil was swept up in the broad sell-off in stocks and bonds Thursday, as a combination of weak Chinese manufacturing data and the Federal's Reserve's shifting stance on economic stimulus rattled energy markets.

Oil had its biggest one-day price drop since November. U.S. benchmark oil for July delivery sank $2.84, or 2.9 percent, to finish at $95.40 a barrel in New York. Gasoline futures fell more than 3 percent.

On Wednesday Fed chairman Ben Bernanke suggested that he was optimistic about the U.S. economy ? and that the Fed might start scaling back its massive $85 billion-a-month bond-buying program this year if conditions continue to improve. The Fed could end the program by the middle of next year, Bernanke said.

The Fed program has kept borrowing costs near historic lows for consumers and business. It has also helped boost the equities and energy markets.

Stocks and bonds sold off immediately after Bernanke's comments. Oil didn't react much because Bernanke spoke just as U.S. energy markets closed Wednesday.

Lower stocks and a stronger dollar put pressure on oil prices. Once trading opened in Asia Thursday oil fell sharply, in tandem with Asian stock markets. Bernanke's comments also gave a boost to the dollar. Oil traders look to the stock market as a measure of confidence in the U.S. economy, while a strong dollar makes oil more expensive for holders of other currencies.

The Dow Jones industrial average fell 354 points, or 2.3 percent, Thursday to close at 14,758. Shares of Exxon Mobil Corp. and Chevron Corp., both Dow components, fell by more than 2 percent. The euro slipped to $1.3197 from $1.3274 in New York a day earlier. The yield on the benchmark 10-year note rose to its highest level since August 2011.

Also weighing on oil prices was a survey showing a slowdown in manufacturing in China. HSBC's preliminary purchasing managers' index fell to a nine-month low of 48.3 in June, down from 49.6 in May. Numbers below 50 indicate a contraction.

With mature economies like Europe and the U.S. struggling to expand at a steady pace, China and emerging markets have accounted for most of the growth in oil demand over the past several years.

"A weakening in Chinese industrial activity could easily translate to a reduced flow of products exports out of the US Gulf," said Jim Ritterbusch, president of energy consultancy Ritterbusch and Associates, in a daily report.

Still, Ritterbusch and most others don't expect a free-fall in the price of oil. He said fears of an escalation of the civil war in Syria should support oil around the $94 level.

Brent crude, a benchmark for many international oil varieties, was down $3.97, or 3.7 percent, to end at $102.94 per barrel on the ICE Futures exchange in London.

In other energy futures trading on the Nymex:

? Wholesale gasoline was down 10.5 cents, or 3.6 percent, to finish at $2.79 a gallon.

? Heating oil fell 10 cents, or 3.4 percent, to end at $2.87 per gallon.

? Natural gas retreated by 9 cents, or 2.2 percent, to finish at $3.88 per 1,000 cubic feet.

___

Pablo Gorondi in Budapest and Pamela Sampson in Bangkok contributed to this report.

Source: http://news.yahoo.com/oil-falls-most-since-november-fed-comments-161536781.html

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US calls out China, Russia over human trafficking

WASHINGTON (AP) ? The U.S. accused China and Russia of failing to meet minimum standards in fighting human trafficking, ranking them on a par with North Korea and Syria.

The State Department downgraded China and Russia in rankings on how 188 governments around the world have performed in fighting the flesh trade and other forms of exploitative labor.

Rights activists are welcoming the move, but it could further strain Washington's touchy relations with the two world powers.

The U.S. also downgraded Uzbekistan over its state-sanctioned use of forced labor in the annual cotton harvest.

The rankings are in the department's annual report released Wednesday.

President Barack Obama now has 90 days to determine whether to apply sanctions against China, Russia, Uzbekistan and 18 other governments given a "tier three" ranking ? the lowest the department gives.

The president can block various types of aid, such as arms financing, grants for cultural and educational exchange programs and could withdraw U.S. support for loans from the World Bank and International Monetary Fund.

That appears unlikely in the cases of China, Russia and Uzbekistan, which have strategic importance for Washington.

Obama is looking to cooperate more closely with emerging Asian superpower China after meeting its leader Xi Jinping last week; he already faces growing friction with Russia over its support for the Assad regime in war-wracked Syria; and the Central Asian nation of Uzbekistan is important as a transit point as the U.S. pulls out its military from Afghanistan.

Because of a legislative requirement that came into force this year, the Obama administration had to make a judgment whether to downgrade or upgrade the three nations from a "watch list" they were on for several years.

Three others in the same position ? Azerbaijan, Congo and Iraq ? were promoted to "tier two" for progress made in the past year.

"Modern-day slavery affects every country in the world, including the United States and every government is responsible for dealing with it and no government is yet doing enough," Secretary of State John Kerry said at the launch of the report, which he conceded "pulls no punches."

"This report is tough because this is a tough issue and it demands serious attention and that's precisely what we intend to provide."

Activists commended Kerry for being willing to downgrade powerful nations.

"Frankly, we expected a number of these countries to be upgraded for geopolitical reasons," said David Abramowitz, director of the U.S.-based Alliance to End Slavery and Trafficking. "The Trafficking in Persons report is only effective when it's honest."

John Sifton of Human Rights Watch said it remains to be seen whether the White House will execute sanctions. He urged the administration to do so unless the governments in question commit to fight trafficking.

China responded that it has made "unremitting efforts" that have seen a decrease in human trafficking in the country, and in April its governing State Council issued an plan in accordance with international conventions and Chinese laws, aiming for a long-term solution to the problem.

Geng Shuang, the Chinese Embassy spokesman in Washington, said the U.S. report "disregards our efforts in combating human trafficking and makes irresponsible judgment on other countries' internal policy and practice." He called for the U.S. to foster "a more favorable environment" for international anti-trafficking efforts.

The Russian Embassy did not respond to an email seeking comment.

The State Department also put Malaysia and Thailand, a U.S. treaty ally, on notice that they would be downgraded next year to tier three unless they improve anti-trafficking efforts. Abramowitz said it showed that those Southeast Asian nations can't count on their political relationship with the U.S. to avoid censure.

Luis CdeBaca, U.S. ambassador-at-large for human trafficking issues, voiced concern over Thai authorities' treatment of Myanmar migrants, including minority Muslims fleeing a wave of sectarian violence at home. He also referred to "very grave" problems with Malaysia's treatment of trafficking victims, who are held in prison-camp type conditions before deportation.

The Trafficking in Persons report is one of several annual assessments issued by the State Department on human rights-related topics, but it's unusual in that it ranks nations, which can ruffle diplomatic feathers. It is based on the actions governments take, rather than the scale of the problem in their country.

The United States is also scrutinized in the report. It is among 30 countries on "tier one" ? judged to meet minimum standards of combating human trafficking.

According to CdeBaca, the report is intended to prod governments to act and strengthen the hand of civil society organizations in fighting trafficking and forced labor. He said the U.S. seeks to help nations improve their ranking through technical assistance and law enforcement cooperation.

The report criticized China's government for perpetuating trafficking through its use of forced labor in more than 300 state-run prison camps, and its forcible deportation of North Korean trafficking victims, who may face the death penalty on their return home. Girls from Tibet are reportedly trafficked to other parts of China for domestic servitude and forced marriage, it said.

Republican Rep. Chris Smith, an arch critic of Beijing and an author of anti-trafficking legislation, welcomed China's downgrade as recognition that it "has become the sex and labor trafficking capital of the world."

CdeBaca was more conciliatory. He acknowledged China's recent national action plan to combat trafficking, and noted reports China plans to end the practice of re-education through labor. He indicated that if those plans lead to results, it would count in China's favor in next year's report.

On Russia, he said the main concern was authorities' failure to provide care for victims of human trafficking.

An estimated one million people in the country are exposed to "exploitative" labor conditions, including migrants from Europe, Central Asia, and Asia, according to the report. Among them are between 10,000 and 15,000 North Korean workers employed at logging camps in Russia's far east, under an arrangement between the two governments. The workers reportedly have only two days of rest per year and face punishments if they fail to meet production targets.

There are now 25 nations sitting on the department's watch list that could be downgraded to tier three next year. That relegation can be waived for two years, if governments demonstrate they have a plan to address human trafficking and commit resources to implement it.

Of the 25, six countries ? Thailand, Malaysia, Afghanistan, Barbados, Chad and the Maldives ? are entering their second year of being waived. Each faces an automatic downgrade in 2014 unless they demonstrate progress.

Source: http://news.yahoo.com/us-calls-china-russia-over-human-trafficking-201931607.html

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New details about H7N9 influenza infections that suddenly appeared in China

June 19, 2013 ? Researchers with the Network Dynamics and Simulation Science Laboratory at the Virginia Bioinformatics Institute have revealed new information about the latest strain of type A influenza, known as H7N9, in a report in the journal PLOS Currents: Outbreaks.

Since June 7, 132 confirmed cases of human infection with H7N9 have been reported in China and 37 people have died, according to the World Health Organization. It is the first time human infection with the avian influenza H7N9 subtype has been detected, and researchers fear that this strain may have pandemic potential.

The possibility of an animal source of the infection is being investigated, as is the possibility of person-to-person transmission.

However, most people who contracted the disease reported having contact with live birds in a bird market prior to infection. Researchers at the Network Dynamics and Simulation Science Laboratory found that younger women generally have the most contact with poultry, but it is older men who are experiencing the most infections.

The findings suggest that there is something unique about older men that makes them particularly susceptible to H7N9. Their greater risk of infection is not just because they tend to spend more time exposed to an avian source.

Researchers quickly compiled the data using a variety of available sources to discover risk factors, which could aid in containing the spread of H7N9.

"Normally we have to wait for epidemiologists to collect new data in the early days if an outbreak. We were able to combine data from existing sources in an innovative way to rapidly learn about H7N9 risk factors," said Caitlin Rivers of Plainfield, N.H., a graduate student majoring in genetics, bioinformatics, and computational biology and research assistant at the Network Dynamics and Simulation Science Laboratory.

To contain the spread of this strain of influenza, some Chinese live bird markets have been closed. It may help, but still does not explain the high infection rate of older men. Further studies are required to understand what other factors may be involved in transmission to help contain H7N9's spread.

"In keeping with a commitment to open science, the raw data and calculations are available publicly. We invite others to use and expand upon this work," said Bryan Lewis, a public health policy analyst with the Virginia Bioinformatics Institute.

This work has been partially supported by NIH MIDAS Grant 2U01GM070694-09 and NIH MIDAS Grant 3U01FM070694-09S1.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/Ey3CqK6WrJI/130619164847.htm

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Tuesday, April 16, 2013

Ruth and Female Bodyspace Model Search Finalists At 2010 Fit Expo

Videos | April 15, 2013 11:55 am

Hundreds of fitness enthusiasts attended the 2013 Health and Fitness Expo at Graves Fitness Center Jan. 17 to learn about Fort Belvoir?s wide range of exercise programs, participate in aerobics workouts with certified instructors and visit with several workout program and equipment vendors from the local area.
The event, sponsored by the Fort Belvoir Directorate of Family and Morale, Welfare and Recreation Sports and Fitness, aimed to promote healthy physical activity and proper nutritional habits to everyone who lives, works and plays on the installation.
?This is intended to bring together a lot of fitness sources to celebrate health,? said Debra Taylor, Fort Belvoir DFMWR marketing director. ?Everybody is trying to get healthy in January so we thought this would be a good time to help people push to do that.

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Source: http://stek.org/videos/ruth-and-female-bodyspace-model-search-finalists-at-2010-fit-expo/

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'Not a death in vain': Kerry to meet parents of US diplomat killed by Afghan car bomb

Smedinghoff family via Reuters

Anne Smedinghoff, a 25-year-old diplomat from River Forest, Illinois, was killed along with four other Americans in a car bomb blast in Afghanistan on April 6.

By Andrea Mitchell and Ian Johnston, NBC News

Secretary of State John Kerry was due on Monday to meet the parents of Anne Smedinghoff, the American diplomat killed in a car bombing in Afghanistan earlier this month.

Kerry was scheduled to meet them in Chicago after flying back from Japan following a six-nation tour in Asia dominated by the North Korean crisis.

Smedinghoff, 25, was on her way to deliver books to a school in Qalat, Zabul province, when she and four other Americans were killed by a car bomb on April 6. An American civilian was also killed in a separate attack on the same day.

Anne Smedinghoff, 25, was killed Saturday when a suicide car bomber blew up their convoy along with four other Americans. Although she recognized the dangers and risks in Afghanistan, her family and friends said she still loved the job. NBC's Stephanie Gosk reports.

Kerry, speaking in Tokyo, said that everyone he had met with in recent days in the State Department ?feels this enormously.?

?It's all the promise of a young person with all of the idealism and energy, enthusiasm suddenly snuffed out in the quest of high ideals and great values,? he said.?

?I think that ? is not a death in vain. It's a loss. It's a horrible loss. It's unfathomable as a parent,? he said. ?But it's a great contribution and sacrifice for our country. And it is in the highest spirit of tradition and service of the State Department and the Foreign Service, and indeed of America, in our efforts to try to help other people be able to share in the blessings of life that we experience every day.?

?So I think that people should celebrate her life and really show their respect for what she was trying to do,? he added. ?She inspired a lot of people and even in her loss she's an inspiration.?

Kerry met Smedinghoff, whose business card read "Assistant Information Officer," several weeks ago when she worked as his control officer during his recent trip to Afghanistan.

Smedinghoff previously served in Venezuela.

In an email to the Washington Post, Smedinghoff's parents said their daughter "was always looking for opportunities to reach out and help to make a difference in the lives of those living in a country ravaged by war."

They added: "We are consoled knowing that she was doing what she loved, and that she was serving her country by helping to make a positive difference in the world."

Related:

'She was doing what she loved': Young diplomat among 6 Americans killed in Afghanistan

'We have to go': Afghans ready to flee country as foreign troops withdraw

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Falling commodities give Dow worst day of the year

NEW YORK (AP) ? Worries about an economic slowdown in China fueled a steep drop in commodity prices Monday, spooking investors and giving the stock market its worst day of the year.

The trigger for the sell-off came from China, where the world's second-largest economy expanded 7.7 percent in the first three months of the year, well below forecasts of 8 percent or better. That news pummeled copper, oil and other commodities. Shares of oil and mining companies fared the worst because China is a huge importer of their products.

The decline came after a pile of negative economic reports. In addition to the concerns about China, a separate report showed weak manufacturing in the Northeast, and a home builders' survey indicated housing activity isn't going to be strong, either, said Steven Ricchiuto, chief economist for Mizuho Securities.

"People are realizing that the global economy isn't as strong as they expected it to be," he said.

The market began tumbling hours before reports emerged of two bombs exploding in the packed streets near the finish line of the Boston Marathon. The attack that killed two people and injured more than 100 was just one more thing to worry investors.

The pullback disrupted, at least for the moment, the phenomenal rally that has sent the Dow Jones industrial average up 13 percent and the Standard & Poor's 500 index up 11 percent in 2013. Both indexes marked record highs only last Wednesday. But the market's exceptional performance has fueled widespread speculation about an inevitable retreat.

Concerns that Cyprus and other troubled European countries may sell gold to raise cash have also weighed on prices for precious metals, said Dan Greenhaus, chief global strategist at the brokerage BTIG.

The Dow tumbled 265.86 points to close at 14,599.20, a decline of 1.8 percent. Caterpillar, a maker of heavy equipment used by miners, led the index lower, falling 3 percent to $82.27. The S&P 500 index slumped 36.48 points to 1,552.37, a loss of 2.3 percent.

The S&P was led by Freeport-McMoRan Copper & Gold, which fell 8 percent to $29.27. Analysts at Citigroup placed a "sell" rating on the mining giant on the expectation that copper prices will continue sliding.

The Nasdaq composite fell 78.46 points, or 2.4 percent, to 3,216.49.

It was the biggest drop for the stock market since Nov. 7 ? Election Day ? last year.

Of the 10 industry groups in the S&P 500, materials and energy stocks fared the worst, losing 4 percent. Indexes of small companies and transportation stocks, which are more vulnerable to swings in the economy, also fell 4 percent.

Crude oil prices hit their lowest level since mid-December, sliding $2.58 to finish at $88.71 in New York trading. And gold fell $140, plunging below $1,400 an ounce for the first time in two years as a sell-off in metals continued from last week. Gold has now slumped $203 an ounce over the past two days.

Frank Fantozzi, CEO of Planned Financial Services, a wealth management firm, says people had bought gold since the financial crisis on the belief that it was safe place to keep money. But now that the metal has slid 20 percent this year, they're jumping out.

"I think you're getting some panic selling right now" in the gold market, Fantozzi said. "People who have been holding on to gold expecting a rebound are now thinking, 'I better get out.'"

Cetin Ciner, a finance professor and expert in precious metal markets at the University of North Carolina, Wilmington, said gold had also offered a protection against rampant inflation when the economy recovered. That helped push gold prices as high at $1,900 in 2011, but the high inflation they worried about still hasn't hit.

Gold "was bound to collapse at some stage," Ciner said. "People were waiting and waiting for higher inflation, and they finally realized it's not happening."

Just seven stocks rose in the S&P 500. Among them, Citigroup inched up 9 cents to $45.87, after the country's third-largest bank reported earnings that beat analysts' estimates. Stronger revenue from trading and investment banking lifted the bank's results.

Sprint Nextel jumped after Dish Network offered $25 billion to buy the company. Dish's bid is aimed at beating an offer from the Japanese phone company SoftBank. Sprint surged 14 percent to $7.06, and Dish fell 2 percent to $36.77.

Thermo Fisher Scientific offered $13.6 billion to buy genetic testing equipment maker Life Technologies. That works out to $76 in cash for each share of Life Technologies. Thermo Fisher's stock fell 1 percent to $78.58, while Life Technologies rose 7 percent to $73.11.

In the market for U.S. government bonds, which traders often buy when they're concerned about the economy, the yield on the 10-year Treasury note retreated to 1.69 percent, its lowest level of the year. That's down from 1.72 percent late Friday.

But for all the alarm among investors, experts doubt that the drop in stock prices is a harbinger of another global recession. Deep government budget cuts have slowed the U.S. economy and kept Europe in recession. And China's economy is cooling. But economists still expect the U.S. economy ? the world's biggest ? to gain strength during the second half of the year.

Nearly four years after the Great Recession ended, the American economy has a stronger foundation. Rising home prices and near-record stock prices make consumers feel wealthier and more willing to spend. And although China's growth was below expectations, it was still a pace that would be considered strong anywhere else.

The broader outlook for stocks was not likely to be "tremendously affected" by Monday's sell-off, Ciner said.

"There's so much money being pumped into the system, and the money has to go somewhere," he said, referring to the more than $2 trillion in bonds the Federal Reserve has bought since the Great Recession.

And there's ample evidence that the U.S. economy is making substantial improvements.

"There is some growth. Profits are up. So I don't think commodities will affect stocks," Ciner said. "There may be some volatility, but I think stocks will continue to go up in the short term."

___

Associated Press Business Writers Paul Wiseman in Washington and Bernard Condon in New York contributed to this report.

Source: http://news.yahoo.com/falling-commodities-dow-worst-day-222420116--finance.html

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Monday, April 15, 2013

Haemorrhoids - All4Women Health Articles

Haemorrhoids

Photo ?: Lifting heavy objects - Fotolia.com


Hemorrhoids are one of the most common colorectal conditions with an estimated 50% of the population experiencing it by the age of 50 years.

Causes

It has not yet been determined as to what the exact cause of haemorrhoids is but the following factors seem to contribute to a person having the condition:

???? Low dietary fibre intake
???? Malnutrition with constipation
???? A decrease in physical activity
??? ?Genetics

Risk

People whose jobs involve lifting heaving objects or prolonged standing are at risk of getting haemorrhoids together with those who overuse stimulant laxatives. Pregnancy and labour may aggravate the condition as well.

Symptoms

Symptoms of haemorrhoids include:

? rectal bleeding

? protrusion and swelling of tissue outside the anal canal

? itching secondary to inflammation

* It is generally painless, unless the protrusion becomes thrombosed, infected or ulcerated

Note that these symptoms are nonspecific and that conditions such as inflammatory bowel disease and cancer can have the same haemorrhoidal symptoms.

Treatment

Over-the-counter medications, dietary as well as lifestyle modifications are usually recommended to help treat haemorrhoids.
Further medical intervention may be required if the above does not help the patient.

Prevention

Prevent haemorrhoids by:

???? Avoid excessive pressure and straining during defecation
??? ?Increase intake of high-fibre diet
??? ?Drink plenty of water
??? ?Exercise

Source: Healthplus24

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Source: http://all4women.co.za/health-and-wellness/health-articles/hemorrhoids.html

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State Street electronic FX chief departs in shake-up

By Tim McLaughlin

BOSTON (Reuters) - State Street Corp said on Saturday the top executive of its electronic foreign exchange trading business has left the company in a leadership shake-up.

The departure of Clifford Lewis raises questions about the direction of Boston-based State Street's high-frequency trading platform for forex called Currenex. Lewis was chief executive and chairman of Currenex when State Street agreed in 2007 to buy the company for nearly $600 million in cash.

"Because we have combined teams and solutions that previously resided within other business units, we've had to make tough decisions about leadership, and Cliff Lewis left as a result of those decisions," said State Street spokeswoman Carolyn Cichon. "We are very grateful for the contributions he has made and strong management team that he leaves behind."

On Friday, State Street said Jeff Conway would oversee a global exchange group that included electronic FX trading, data analytics and derivatives clearing.

Lewis was not mentioned in the reorganization announcement. He did not return messages seeking comment.

Lewis was an executive vice president at State Street and head of the e-Exchange business, which includes Currenex, FXConnect and a range of other trading platforms. The e-Exchange FX businesses averaged over $150 billion in daily volume in 2012, making them one of the largest FX trading platforms in the world. Lewis also managed State Street's derivatives and bond clearing businesses.

Last year, though, State Street's revenue from electronic forex trading fell 16 percent to $210 million from $249 million in 2011, according to company financial statements. The company blamed declines in currency volatility and pricing. Total FX trading revenue at State Street fell 25 percent in 2012.

Part of the drop was related to a shift away from non-negotiated FX trades by State Street customers, such as state-run pension funds. On those trades, it has been alleged that State Street had been overcharging customers, an accusation the company has steadfastly denied.

Lewis' operations did not include non-negotiated trades. Instead, Currenex, for example, focused on sophisticated algorithmic trading, which uses computers to place orders that sometimes are executed within milliseconds.

These high-frequency FX trades are a big area for potential growth at banks. Computer-run algorithms allow hedge funds, for example, to unload large amounts of currencies without tipping their hand. They can also read and interpret news and economic data releases, generating trading orders before the rest of the forex market is fully aware of what is happening.

(Reporting By Tim McLaughlin; editing by Christopher Wilson and Gunna Dickson)

Source: http://news.yahoo.com/state-street-electronic-fx-chief-departs-leadership-shake-180220787--sector.html

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Sunday, April 14, 2013

Irritable Bowel Syndrome | Natural Holistic Health Blog

Are you having problems with your digestion? If it involves the lower half of the digestive tract it could be irritable bowel syndrome. Here are some facts to help you decide.

Irritable bowel syndrome, or IBS, is a condition involving the intestines. There are no clear-cut causes of the condition but it can lead to very painful situations for those affected.

In the intestinal tract, different triggers cause bowels to move differently than they did before. There are usually no visible signs such as inflammation, polyps or tumors that signal that irritable bowel is going on. Those who suffer from IBS often experience abdominal cramping, diarrhea, pain in the abdomen and constipation.

Those who have this condition also deal with bloating and gas. The symptoms may swing from diarrhea to constipation at different times. Doctors can help diagnose it from your description of your symptoms and a physical exam.

Who is at risk for irritable bowel syndrome? Those who have a family history won?t necessarily develop the condition but the odds are not in their favor. It usually occurs in women more than men and young people more so than older adults.

People with certain mental disorders (like depression and psychological trauma) are at risk. Also, those who have experienced abuse in their past, have a greater risk of developing irritable bowel syndrome than others. Fibromyalgia is also a risk factor because it affects the muscles throughout the body.

Once you develop irritable bowel syndrome, you will always have it. Managing the pain involves knowing your triggers and treating the symptoms. Your doctor may perform an endoscopic procedure to look at your intestine and see if something else is going on there that could be causing similar symptoms.

How can you treat the symptoms of IBS? First examine your lifestyle. While there is no direct correlation between food and irritable bowel syndrome, people often experience attacks after they eat. Learning food triggers is one step.

Stress can cause all types of reactions in the body. When it is unmanaged, it can cause gastrointestinal problems. Learning to handle situations in your life that are leading to stress, can reduce its part in the problem.

Exercise helps to bring the body back into optimal health. When the body is receiving proper nutrition and maintains a healthy weight, it is easier for the immune system to fight against illness. Regular physical activity may alleviate some of the symptoms of IBS.

Do you have gastrointestinal problems? See your doctor because you may be suffering from irritable bowel syndrome. While it affects the colon, your symptoms can be controlled through lifestyle changes and medication.

Your doctor may also prescribe medication if diet and exercise don?t make any significant change.

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About Dee Braun

Dee is an Adv. Certified Aromatherapist, Reiki Master, Adv. Color/Crystal Therapist, Herbalist, Dr. of Reflexology and single mom who is dedicated to helping others any way she can. One way she chooses to help is by offering information on the benefits and uses of natural health and healing methods for the well-being of both people and pets. Dee also teaches Aromatherapy, Reflexology and Color/Crystal Therapy at the Alternative Healing Academy

Source: http://www.natural-holistic-health.com/irritable-bowel-syndrome/?utm_source=rss&utm_medium=rss&utm_campaign=irritable-bowel-syndrome

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US publishes list of 18 alleged human rights abusers in Russia

By Susan Cornwell, Reuters

The Obama administration on Friday designated 18 people under a U.S. law requiring a list of alleged human rights abusers in Russia, in a move that could cause more friction in U.S. ties with Moscow.

The list includes 16 people directly related to the case of Russian whistleblower Sergei Magnitsky, who died in his jail cell in 2009, as well as two others, a senior State Department official said on condition of anonymity. Those named on the list will be subject to visa bans and asset freezes in the United States under a law passed by Congress last year.

One U.S. lawmaker said the list was "timid" with "significant omissions," while a senior Russian lawmaker said he thought President Barack Obama had done the minimum possible under the law so as not to worsen ties with Moscow.

U.S.-Russia relations are strained by what critics say is a crackdown on dissent in Russia under President Vladimir Putin, and disputes over security issues such as the war in Syria, which is a Russian ally.


"The appearance of any lists will doubtless have a very negative effect on bilateral Russian-American relations," Putin's spokesman, Dmitry Peskov, said in Siberia earlier on Friday. Peskov could not be reached for comment once the names on the list were known.

But Alexei Pushkov, the head of the State Duma's international affairs committee, said the United States drew up a "minimal" list.

"The U.S. presidential administration decided not to take the path of aggravating a political crisis with Moscow," Pushkov was quoted as saying by Interfax after the list was released.

The list was published three days before Obama's national security adviser, Tom Donilon, is due in Moscow for talks that Russia said would include U.S. missile defense plans.

The names released by the U.S. Treasury's Office of Foreign Assets Control included several officials who worked in the Russian Interior Ministry, and others who worked in courts, prosecutors' or tax offices.

Also listed was Kazbek Dukuzov, one of two natives of the Chechnya region who were tried for the 2004 killing in Moscow of American journalist Paul Klebnikov. Both were acquitted in 2006.

Not listed was a close Putin ally whom some human rights advocates wanted to see named - Alexander Bastrykin, who heads Russia's equivalent of the FBI. He has said there is no evidence Magnitsky death was connected with actions by officials.

Putin has said that Magnitsky's death at age 37 was caused by heart failure. But the Kremlin's own human rights council has aired suspicions that Magnitsky was beaten to death. His death spooked investors and tarnished Russia's image abroad.

Congress passed the Magnitsky Act in December as part of a broader bill to expand U.S. trade with Russia. The Obama administration was never keen on the Magnitsky provisions, but the president signed the bill into law in December.

The law requires an initial list by Saturday of people linked to the Magnitsky case or other alleged "gross violations of internationally-recognized human rights" in Russia.

Russia considers the Magnitsky Act outside interference in its affairs, and warns it may respond by issuing a list of alleged U.S. human rights abusers. Moscow has already retaliated by outlawing adoptions of Russian children by American couples.

'Significant omissions'
Democratic Rep. James McGovern, one of the sponsors of the Magnitsky Act, called the list "timid" with "significant omissions." Late last month, McGovern sent the White House over 230 names of people he said could potentially be included.

Not on the list but named in the Magnitsky Act itself for "wrongdoing" is Ramzan Kadyrov, the Kremlin-backed leader of Russia's Chechnya region.

Kadyrov has not been linked to the Magnitsky case, but the U.S. State Department has noted allegations of his involvement in several killings, including that of human rights worker Natalia Estemirova. Kadyrov has denied involvement.

McGovern said in a statement he was told by the administration that the investigation was continuing and more names would be added as new evidence came to light.

The senior State Department official denied that political or diplomatic concerns were a factor in drawing up the list.

"I've learned not to try to take action based on what you think the Russian reaction might be. It's better to do what's in the law and what's right and what reflects American interests and American values on human rights, and then you let the chips fall where they may," the official said. "We played this one straight. We haven't tried to game it."

Russia expert Matt Rojansky of the Carnegie Endowment think tank said, "It makes a lot of sense that the administration would not want to deepen the tension in relations" on the eve of the Donilon trip to Moscow. Rojansky said Donilon's visit was expected to include discussions of a possible Obama-Putin meeting at a gathering of the G-8 in Northern Ireland in June.

Rojansky noted there was also a classified annex to the list, which might include more politically sensitive names.

But Republican Sen. John McCain, who presumably had seen the classified annex, said in a statement about the classified part, "Even that list is inadequate."

Magnitsky worked for the investment fund Hermitage Capital Management in Moscow and was arrested on tax fraud charges shortly after he leveled similar accusations against Russian state officials in 2008.

Magnitsky is now being tried posthumously for tax evasion in Moscow.

The U.S. list included a number of people U.S. lawmakers and rights activists have urged be listed because of alleged links to the jailing of Magnitsky or a cover-up over his death.

Among them were Oleg Silchenko, a senior investigator at the federal Interior Ministry, who was allegedly in charge of the investigation into Magnitsky and ordered his detention.

Also named was Pavel Karpov, a senior investigator in the Interior Ministry at the time of the 2007 police raids on Hermitage Capital, and Artyom Kuznetsov, another Interior Ministry official who allegedly took part in the police raids.

Karpov, who has initiated a libel case against William Browder, the chief of Hermitage Capital, denied the accusations.

"I am expecting soon the decision from the high court of London which will confirm the falsehood of the accusation" Karpov told Interfax.

The list also included Olga Stepanova, an official from the Moscow Tax Office that authorized part of a $230 million tax refund that Magnitsky had told officials was suspect.

Another name on the list was Yelena Stashina, a judge who allegedly prolonged Magnitsky's detention, and Andrey Pechegin, who worked in the general prosecutor's office and allegedly denied complaints from Magnitsky about his treatment.

In addition to Dukuzov, the other name unrelated to the Magnitsky case was Lecha Bogatyrov, who has been implicated in the killing of Umar Israilov, a former bodyguard of the Russian Chechen leader Kadyrov. Israilov was shot to death in Vienna in 2009 after turning against Kadyrov. Bogatyrov reportedly escaped arrest and returned to Russia.

Copyright 2013 Thomson Reuters. Click for restrictions.

Source: http://feeds.nbcnews.com/c/35002/f/653387/s/2aa932f5/l/0Lworldnews0Bnbcnews0N0C0Inews0C20A130C0A40C120C177254640Eus0Epublishes0Elist0Eof0E180Ealleged0Ehuman0Erights0Eabusers0Ein0Erussia0Dlite/story01.htm

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Monitoring the Monarchs

Last month monarch butterflies began an annual northward journey from their overwintering habitat in Mexico. Monarch expert Lincoln Brower discusses the dwindling monarch populations, and explains how habitat loss in Mexico and a decline in milkweed plant numbers in the U.S. may be harming the familiar orange and black fliers.

Source: http://www.npr.org/2013/04/12/177029257/monitoring-the-monarchs?ft=1&f=1007

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Saturday, April 13, 2013

Guards, detainees clash in pre-dawn raid at Guantanamo

Bob Strong / Reuters, file

An unidentified prisoner reads a newspaper in a communal cellblock at Camp VI, a prison used to house detainees at Guantanamo Bay U.S. Naval Base, March 5, 2013.

By Michael Isikoff, National Investigative Correspondent, NBC News

U.S. military guards raided the largest camp at Guantanamo Bay early Saturday morning and fired four non-lethal shots as they moved detainees into solitary cells to suppress a widening protest, military officials said in a statement.

The unusual pre-dawn raid, ordered by Cmdr. Rear Adm. John W. Smith, was prompted by detainees' efforts to cover surveillance cameras, windows and glass partitions -- blocking views by guards -- amid an ongoing hunger strike that has now spread to more than 40 detainees and required officials to order some prisoners to be force fed through tubes. ??

During the raid, "some detainees resisted with improvised weapons, and in response, four less-than-lethal rounds were fired. There were no serious injuries to guards or detainees," according to the statement released by the Joint Task Force at Guantanamo.

Carlos Warner, a lawyer who represents detainees, said in an email to NBC News the raid was "a major event" and accused military officials of "escalating the conflict."


Warner also said the military timed the raid just after an International Red Cross delegation left the facility.

?They are doing exactly what they shouldn't be doing - provoking men who have nothing to lose and who are ready to die. These actions will drive the men closer to death, so yes the situation is rapidly deteriorating,? he added.

The U.S. military says guards raided a camp and fired four non-lethal rounds in response to detainees' efforts to cover surveillance cameras and windows during a hunger strike. MSNBC's Mara Schiavocampo reports.

A White House spokesperson said: "We have been monitoring the situation at Guantanamo closely and were informed by DOD in advance of the Task Force's plan to transition detainees at Camp VI from communal to single-cell living to ensure their health and security."

In recent weeks, as the hunger strike has spread among detainees, human rights groups have called on the Obama administration to fulfill its promise to shut down Guantanamo and step? up its efforts to return detainees who have been cleared for release to their home countries.

Lawyers for the detainees said they have been told of detainees losing consciousness and coughing up blood due to the hunger strike.

The Saturday morning raid occurred in Camp VI -- the largest at Guantanamo -- where detainees deemed "compliant" live in communal areas and are given special privileges. But military officials said that, in order to "reestablish proper observation" of the detainees, military forces began moving the detainees back into "single cell" confinement, triggering the resistance that led them to fire shots. Officials have said in the past that guards are equipped with rubber bullets.

Last month, U.S. military officials denied any detainees' lives were in danger but acknowledged that resistance and frustration among the detainees is growing, a development that a senior general said is because they are ?devastated? that President Barack Obama?s pledge to shut down the facility has not been fulfilled.

White House officials say they remain committed to closing Guantanamo but have been blocked from doing so by Congress, leading officials to close the small State Department office charged with finding new homes for the detainees.

Related:

Pentagon ponders Gitmo overhaul amid growing detainee unrest

'Non-lethal round' fired at Gitmo detainees in soccer field incident, US military confirms

Source: http://feeds.nbcnews.com/c/35002/f/653387/s/2aae8904/l/0Lworldnews0Bnbcnews0N0C0Inews0C20A130C0A40C130C177365990Eguards0Edetainees0Eclash0Ein0Epre0Edawn0Eraid0Eat0Eguantanamo0Dlite/story01.htm

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Tuesday, April 9, 2013

Economist's View: Paul Krugman: Insurance and Freedom

Social insurance does not undermine free societies:

Insurance and Freedom, by Paul Krugman, Commentary, NY Times: ...How many Americans will be denied essential health care in the name of freedom?
I?m referring, of course, to the question of how many Republican governors will reject the Medicaid expansion that is a key part of Obamacare. What does that have to do with freedom? In reality, nothing. But when it comes to politics, it?s a different story. ... From the enthusiastic reception American conservatives gave Friedrich Hayek?s ?Road to Serfdom,? to Reagan, to the governors now standing in the way of Medicaid expansion, the U.S. right has sought to portray its position not as a matter of comforting the comfortable while afflicting the afflicted, but as a courageous defense of freedom. ...
These days, conservatives make very similar arguments against Obamacare. For example,?Senator Ron Johnson?of Wisconsin has called it the ?greatest assault on freedom in our lifetime.? And this kind of rhetoric matters, because when it comes to the main obstacle now remaining to more or less universal health coverage ? the reluctance of Republican governors to allow the Medicaid expansion that is a key part of reform ? it?s pretty much all the right has. ...
[However], Medicaid enjoys?remarkably strong public support. And now that health reform is the law of the land, the economic and fiscal case for individual states to accept Medicaid expansion is overwhelming. ... But such practical concerns can be set aside if you can successfully argue that insurance is slavery.
Of course, it isn?t. In fact, it?s hard to think of a proposition that has been more thoroughly refuted by history than the notion that social insurance undermines a free society. ...
In fact, the real, lived experience of Obamacare is likely to be one of significantly increased individual freedom. For all our talk of being the land of liberty, those holding one of the dwindling number of jobs that carry decent health benefits often feel anything but free, knowing that if they leave or lose their job, for whatever reason, they may not be able to regain the coverage they need. Over time, as people come to realize that affordable coverage is now guaranteed, it will have a powerful liberating effect.
But what we still don?t know is how many Americans will be denied that kind of liberation ? a denial all the crueler because it will be imposed in the name of freedom.

Posted by Mark Thoma on Monday, April 8, 2013 at 12:33 AM in Economics, Politics, Social Insurance?| Permalink? Comments?(30)

Source: http://economistsview.typepad.com/economistsview/2013/04/paul-krugman-insurance-and-freedom.html

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O2 customers get free pass on Virgin Media's tube WiFi, last 12 stations go online this week

O2 customers get free pass on Virgin Media's tube WiFi, 12 more stations go online this week

Unless you're an EE or Vodafone customer, you've either been shelling out for subterranean internet, or bid the London Underground's WiFi network a solemn farewell when free access ended in January. If you're with O2, however, you're free pass has now been reinstated, as the bubble-loving carrier has become the latest passenger riding on Virgin Media's tube hotspots. Better yet, all O2 clientele have been automatically registered, so jumping online should be pretty simple once your device has found the source. Also, the underground network will shortly be meeting it's 120-station target, as Virgin will be flipping switches at the final 12 locations throughout this week (the station list is available at the source link). So, should you start seeing more people in more places frantically hammering their smartphones during those 30-second pauses on the platform, you'll know why.

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Source: Virgin Media

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Friday, March 29, 2013

New vaccine-design approach targets viruses such as HIV

Mar. 28, 2013 ? A team led by scientists from The Scripps Research Institute (TSRI) and the International AIDS Vaccine Initiative (IAVI) has unveiled a new technique for vaccine design that could be particularly useful against HIV and other fast-changing viruses.

The report, which appears March 28, 2013, in Science Express, the early online edition of the journal Science, offers a step toward solving what has been one of the central problems of modern vaccine design: how to stimulate the immune system to produce the right kind of antibody response to protect against a wide range of viral strains. The researchers demonstrated their new technique by engineering an immunogen (substance that induces immunity) that has promise to reliably initiate an otherwise rare response effective against many types of HIV.

"We're hoping to test this immunogen soon in mice engineered to produce human antibodies, and eventually in humans," said team leader William R. Schief, who is an associate professor of immunology and member of the IAVI Neutralizing Antibody Center at TSRI.

Seeking a Better Way

For highly variable viruses such as HIV and influenza, vaccine researchers want to elicit antibodies that protect against most or all viral strains -- not just a few strains, as seasonal flu vaccines currently on the market. Vaccine researchers have identified several of these broadly neutralizing antibodies from long-term HIV-positive survivors, harvesting antibody-producing B cells from blood samples and then sifting through them to identify those that produce antibodies capable of neutralizing multiple strains of HIV. Such broadly neutralizing antibodies typically work by blocking crucial functional sites on a virus that are conserved among different strains despite high mutation elsewhere.

However, even with these powerful broadly neutralizing antibodies in hand, scientists need to find a way to elicit their production in the body through a vaccine. "For example, to elicit broadly neutralizing antibodies called VRC01-class antibodies that neutralize 90 percent of known HIV strains, you could try using the HIV envelope protein as your immunogen," said Schief, "but you run into the problem that the envelope protein doesn't bind with any detectable affinity to the B cells needed to launch a broadly neutralizing antibody response."

To reliably initiate that VRC01-class antibody response, Schief and his colleagues therefore sought to develop a new method for designing vaccine immunogens.

From Weak to Strong

Joseph Jardine, a TSRI graduate student in the Schief laboratory, evaluated the genes of VRC01-producing B cells in order to deduce the identities of the less mature B cells -- known as germline B cells -- from which they originate. Germline B cells are major targets of modern viral vaccines, because it is the initial stimulation of these B cells and their antibodies that leads to a long-term antibody response.

In response to vaccination, germline B cells could, in principle, mature into the desired VRC01-producing B cells -- but natural HIV proteins fail to bind or stimulate these germline B cells so they cannot get the process started. The team thus set out to design an artificial immunogen that would be successful at achieving this.

Jardine used a protein modeling software suite called Rosetta to improve the binding of VRC01 germline B cell antibodies to HIV's envelope protein. "We asked Rosetta to look for mutations on the side of the HIV envelope protein that would help it bind tightly to our germline antibodies," he said.

Rosetta identified dozens of mutations that could help improve binding to germline antibodies. Jardine then generated libraries that contained all possible combinations of beneficial mutations, resulting in millions of mutants, and screened them using techniques called yeast surface display and FACS. This combination of computational prediction and directed evolution successfully produced a few mutant envelope proteins with high affinity for germline VRC01-class antibodies.

Jardine then focused on making a minimal immunogen -- much smaller than HIV envelope -- and so continued development using the "engineered outer domain (eOD)" previously developed by Po-Ssu Huang in the Schief lab while Schief was at the University of Washington. Several iterative rounds of design and selection using a panel of germline antibodies produced a final, optimized immunogen -- a construct they called eOD-GT6.

A Closer Look

To get a better look at eOD-GT6 and its interaction with germline antibodies, the team turned to the laboratory of Ian A. Wilson, chair of the Department of Integrative Structural and Computational Biology and a member of the IAVI Neutralizing Antibody Center at TSRI.

Jean-Philippe Julien, a senior research associate in the Wilson laboratory, determined the 3D atomic structure of the designed immunogen using X-ray crystallography -- and, in an unusual feat, also determined the crystal structure of a germline VRC01 antibody, plus the structure of the immunogen and antibody bound together.

"We wanted to know whether eOD-GT6 looked the way we anticipated and whether it bound to the antibody in the way that we predicted -- and in both cases the answer was 'yes'," said Julien. "We also were able to identify the key mutations that conferred its reactivity with germline VRC01 antibodies."

Mimicking a Virus

Vaccine researchers know that such an immunogen typically does better at stimulating an antibody response when it is presented not as a single copy but in a closely spaced cluster of multiple copies, and with only its antibody-binding end exposed. "We wanted it to look like a virus," said Sergey Menis, a visiting graduate student in the Schief laboratory.

Menis therefore devised a tiny virus-mimicking particle made from 60 copies of an obscure bacterial enzyme and coated it with 60 copies of eOD-GT6. The particle worked well at activating VRC01 germline B cells and even mature B cells in the lab dish, whereas single-copy eOD-GT6 did not.

"Essentially it's a self-assembling nanoparticle that presents the immunogen in a properly oriented way," Menis said. "We're hoping that this approach can be used not just for an HIV vaccine but for many other vaccines, too."

The next step for the eOD-GT6 immunogen project, said Schief, is to test its ability to stimulate an antibody response in lab animals that are themselves engineered to produce human germline antibodies. The difficulty with testing immunogens that target human germline antibodies is that animals typically used for vaccine testing cannot make those same antibodies. So the team is collaborating with other researchers who are engineering mice to produce human germline antibodies. After that, he hopes to learn how to drive the response, from the activation of the germline B cells all the way to the production of mature, broadly neutralizing VRC01-class antibodies, using a series of designed immunogens.

Schief also hopes they will be able to test their germline-targeting approach in humans sooner rather than later, noting "it will be really important to find out if this works in a human being."

The first authors of the paper, "Rational HIV immunogen design to target specific germline B cell receptors," were Jardine, Julien and Menis. Co-authors were Takayuki Ota and Devin Sok of the Nemazee and Burton laboratories at TSRI, respectively; Travis Nieusma of the Ward laboratory at TSRI; John Mathison of the Ulevitch laboratory at TSRI; Oleksandr Kalyuzhniy and Skye MacPherson, researchers in the Schief laboratory from IAVI and TSRI, respectively; Po-Ssu Huang and David Baker of the University of Washington, Seattle; Andrew McGuire and Leonidas Stamatatos of the Seattle Biomedical Research Institute; and TSRI principal investigators Andrew B. Ward, David Nemazee, Ian A. Wilson, and Dennis R. Burton, who is also head of the IAVI Neutralizing Center at TSRI.

The project was funded in part by IAVI; the National Institutes of Health (AI84817, AI081625 and AI33292); and the Ragon Institute.

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Journal Reference:

  1. Joseph Jardine, Jean-Philippe Julien, Sergey Menis, Takayuki Ota, Oleksandr Kalyuzhniy, Andrew McGuire, Devin Sok, Po-Ssu Huang, Skye MacPherson, Meaghan Jones, Travis Nieusma, John Mathison, David Baker, Andrew B. Ward, Dennis R. Burton, Leonidas Stamatatos, David Nemazee, Ian A. Wilson, and William R. Schief. Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors. Science, 28 March 2013 DOI: 10.1126/science.1234150

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Source: http://feeds.sciencedaily.com/~r/sciencedaily/~3/72Dc77mGmGc/130328161421.htm

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