Monday, April 29, 2013

How does pregnancy reduce breast cancer risk?

Monday, April 29, 2013

Being pregnant while young is known to protect a women against breast cancer. But why? Research in BioMed Central's open access journal Breast Cancer Research finds that Wnt/Notch signalling ratio is decreased in the breast tissue of mice which have given birth, compared to virgin mice of the same age.

Early pregnancy is protective against breast cancer in humans and in rodents. In humans having a child before the age of 20 decreases risk of breast cancer by half. Using microarray analysis researchers from Basel discovered that genes involved in the immune system and differentiation were up-regulated after pregnancy while the activity of genes coding for growth factors was reduced.

The activity of one particular gene Wnt4 was also down-regulated after pregnancy. The protein from this gene (Wnt4) is a feminising protein - absence of this protein propels a foetus towards developing as a boy. Wnt and Notch are opposing components of a system which controls cellular fate within an organism and when the team looked at Notch they found that genes regulated by notch were up-regulated, Notch-stimulating proteins up-regulated and Notch-inhibiting proteins down-regulated.

Wnt/Notch signalling ratio was permanently altered in the basal stem/progenitor cells of mammary tissue of mice by pregnancy. Mohamed Bentires-Alj from the Friedrich Miescher Institute for Biomedical Research, who led this study explained, "The down-regulation of Wnt is the opposite of that seen in many cancers, and this tightened control of Wnt/Notch after pregnancy may be preventing the runaway growth present in cancer."

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Parity induces differentiation and reduces Wnt/Notch signaling ratio and proliferation potential of basal stem/progenitor cells isolated from mouse mammary epithelium

Fabienne Meier-Abt, Emanuela Milani, Tim Roloff, Heike Brinkhaus, Stephan Duss, Dominique S Meyer, Ina Klebba, Piotr J Balwierz, Erik van Nimwegen and Mohamed Bentires-Alj

Breast Cancer Research (in press)

BioMed Central: http://www.biomedcentral.com

Thanks to BioMed Central for this article.

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Source: http://www.labspaces.net/127977/How_does_pregnancy_reduce_breast_cancer_risk_

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Chrysler investing $20M in Toledo plant to support 9-speed auto ...

Chrysler Group Plans to Invest Nearly $20 Million in Toledo Machining Plant

- Investment to increase capacity for production of torque converters for new generation, fuel-efficient nine-speed transmission
- Company's total investment in U.S. facilities over $5.2 billion since June 2009

April 26, 2013 , Auburn Hills, Mich. - Chrysler Group LLC announced today that it will invest $19.6 million in its Toledo Machining Plant in Perrysburg, Ohio, to increase capacity of the torque converter it's machining for the nine-speed transmission. With this announcement, the Company's total investments in its U.S. operations since June 2009 increase to over $5.2 billion.

The new torque converters will be paired with the next generation, fuel efficient nine-speed front-wheel drive transmission being assembled at Chrysler Group's Indiana (Kokomo, Ind.) Transmission Plant I. The new transmission will debut in the 2014 Jeep? Cherokee.

"The new nine-speed transmission is a critical part of our strategy to meet fuel economy requirements over the next several years and Toledo Machining will play an integral role in bringing this transmission to market," said Scott Garberding, Senior Vice President, Manufacturing, Chrysler Group LLC. "Securing this additional investment is a testament to the dedication and commitment of the plant's workforce and helps secure its future long-term."

The investment will fund the installation of new equipment and tooling for additional machining and assembly capacity. Installation is expected to begin in the third quarter of 2014 and will be completed by the end of 2014.

In August 2011, a $72 million investment in Toledo Machining was announced to modernize the plant to produce the eight- and nine-speed torque converters on two new production lines and a new steering column for the Dodge Dart and Jeep Cherokee. These installations will be complete in the third quarter this year.

"We're very pleased that Chrysler is once again investing in the Toledo Machining Plant and the skilled workforce there," said General Holiefield, Vice President and Director, UAW Chrysler Department. "This will help preserve and enhance jobs in the area and give a greater measure of security to our members and their families well into the future."

In February, the Company announced that it was investing $374 million in several of its Kokomo, Ind., facilities, including establishing a new manufacturing site in Tipton, Ind., to increase production capacity of the nine-speed transmission.

Toledo Machining currently produces torque converters for Kokomo Transmission (Ind.), Indiana Transmission I and II (Kokomo, Ind.), Sterling Heights Assembly (Mich.), and Toluca (Mex.).

The plant also produces steering columns for the following assembly plants: Warren Truck (Mich.), Belvidere (Ill.), Sterling Heights (Mich.), Toledo Assembly Complex (Ohio); Windsor (Ont.), Toluca (Mex.), Saltillo (Mex.), Arab American Vehicles (Egypt) and Carabobo (Venezuela).

Source: http://www.autoblog.com/2013/04/28/chrysler-investing-20m-in-toledo-plant-to-support-9-speed-auto/

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Pathological gambling caused by excessive optimism

Apr. 29, 2013 ? Compulsive gamblers suffer from an optimism bias that modifies their subjective representation of probability and affects their decisions in situations involving high-risk monetary wagers. This is the conclusion drawn by Jean-Claude Dreher's research team at the CNC (Centre de Neurosciences Cognitives, CNRS / Universit? Claude Bernard Lyon 1). These findings, published in the May print edition of Psychological Medicine, could help explain and anticipate certain individuals' vulnerability to gambling, and could lead to new therapeutic approaches.

A growing number of gamblers suffer from pathological gambling, a disease that is usually characterized as either a loss of impulse control or a behavioral addiction. It results in an inability to limit the frequency of gambling and the amount of money wagered. This increasingly common psychiatric disorder creates financial, professional and personal hardships that can have severe consequences for the patients and the people around them. The mechanisms responsible for its emergence and development remain largely unknown, which limits the clinician's ability to proceed with a diagnosis, prognosis or effective treatment for this condition.

In this study, the researchers set out to test and verify the hypothesis that links pathological gambling to an alteration of probabilistic reasoning. The capacity to reason in probabilistic terms appears only at an advanced stage of human intellectual development (in fact, the basic concept of probability is not fully understood until the age of 11 or 12). Pioneering research in the late 1970s had already shed light on the difficulties that people experience in situations involving risk or uncertainty. These difficulties are reflected in the development and perpetuation in adults of cognitive biases1 specific to probabilistic decision-making, one of the most common being probability distortion (2).

The researchers conducted an experiment on compulsive gambling patients using a standard experimental economics task and a mathematical model for measuring both probability distortion and a more general optimism bias in relation to high-risk bets. The primary result obtained confirms the general hypothesis of a distortion, associated with pathological gambling, in the subjective representation of probabilities. The results also show that the compulsion to gamble is not explained by an exaggerated distortion of probability, but rather by an increased optimism bias. In other words, regardless of the objective probability of winning a high-risk bet, gamblers tend to act as though this probability were greater than it actually is. The researchers also observed that in the patient population under study, the intensity of this bias was significantly correlated to the severity of the symptoms.

For clinical psychiatrists, the simplicity of the procedure used to reach this conclusion could offer a rapid and reliable way of measuring the representation of probability, thus allowing them to refine both their diagnoses and therapeutic decisions. This study raises many new questions for researchers in the cognitive neurosciences: how does the brain represent the probability of winning? How do the cerebral structures responsible for this representation interact with the structures involved in the development and perpetuation of an addiction? Is a pathological gambler's particular relationship to probability accompanied by an increased sensitivity to reward and/or insensitivity to monetary loss? These important questions are now being investigated at the CNC.

(1) Internal or external influence causing an alteration of human judgment or perception.

(2) Identified by the Nobel laureates Kahneman and Tversky in 1979, probability distortion is characterized by the overestimation of low probabilities and underestimation of high probabilities.

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The above story is reprinted from materials provided by CNRS (D?l?gation Paris Michel-Ange).

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


Journal Reference:

  1. R. Ligneul, G. Sescousse, G. Barbalat, P. Domenech, J.-C. Dreher. Shifted risk preferences in pathological gambling. Psychological Medicine, 2012; 43 (05): 1059 DOI: 10.1017/S0033291712001900

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/most_popular/~3/6ThD_ZBimlQ/130429102400.htm

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International troops should prepare to go into Syria: U.S. senator

WASHINGTON (Reuters) - A group of nations should get troops ready to invade Syria in order to secure possible stocks of chemical weapons, a senior U.S. senator said on Sunday.

Senator John McCain, a Republican from Arizona, said U.S. troops should not go into Syria, but that an international force must "be ready operationally" to go in and prevent Islamic militants involved in Syria's civil war from getting their hands on chemical weapons.

"There are number of caches of these chemical weapons. They cannot fall into the hands of the jihadists," McCain, who was the 2008 Republican presidential candidate and is an influential voice on military issues in the U.S. Senate, told NBC's Meet The Press.

More than 70,000 people have died in Syria's two-year-old civil war, and the White House said on Thursday the Syrian government of President Bashar al-Assad had probably used chemical weapons on a small scale in the conflict.

Syria denies using chemical weapons in the war.

The U.S. fears anti-Assad Islamist rebels affiliated to al Qaeda could seize the chemical weapons, and Washington and its allies have discussed scenarios where tens of thousands of ground troops go into Syria if Assad's government falls.

(Reporting by Jason Lange; editing by Christopher Wilson)

Source: http://news.yahoo.com/international-troops-prepare-syria-u-senator-150852575.html

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efemr Is Snapchat For Twitter Which Can Only End Well

So yeah, efemr is a web app that scrubs tweets after the amount of time you hashtag. Want a tweet gone after five minutes? #5m. Two hours? #2h. You get the gist. More »
    


Source: http://feeds.gawker.com/~r/gizmodo/full/~3/J5jJAarOxd4/efemr-is-snapchat-for-twitter-which-can-only-end-well

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Sunday, April 28, 2013

Today in History

Today is Sunday, April 28, the 118th day of 2013. There are 247 days left in the year.

Today's Highlight in History:

On April 28, 1788, Maryland became the seventh state to ratify the Constitution of the United States.

On this date:

In 1758, the fifth president of the United States, James Monroe, was born in Westmoreland County, Va.

In 1789, rebelling crew members of the British ship HMS Bounty led by Fletcher Christian set Capt. William Bligh and 18 sailors adrift in a launch in the South Pacific. (Bligh and most of the men with him managed to reach Timor in 47 days.)

In 1817, the United States and Britain signed the Rush-Bagot Treaty, which limited the number of naval vessels allowed in the Great Lakes.

In 1918, Gavrilo Princip, the assassin of Archduke Franz Ferdinand of Austria and the archduke's wife, Sophie, died in prison of tuberculosis.

In 1937, former Iraqi president Saddam Hussein was born in the village of al-Oja near the desert town of Tikrit (he was executed in December 2006).

In 1945, Italian dictator Benito Mussolini and his mistress, Clara Petacci, were executed by Italian partisans as they attempted to flee the country.

In 1952, war with Japan officially ended as a treaty signed in San Francisco the year before took effect. Gen. Dwight D. Eisenhower resigned as Supreme Allied commander in Europe; he was succeeded by Gen. Matthew B. Ridgway.

In 1963, at Broadway's Tony Awards, "Who's Afraid of Virginia Woolf?" was named best play while "A Funny Thing Happened on the Way to the Forum" won best musical.

In 1967, heavyweight boxing champion Muhammad Ali refused to be inducted into the Army, the same day General William C. Westmoreland told Congress the U.S. "would prevail in Vietnam."

In 1980, President Jimmy Carter accepted the resignation of Secretary of State Cyrus R. Vance, who had opposed the failed rescue mission aimed at freeing American hostages in Iran. (Vance was succeeded by Edmund Muskie.)

In 1988, a flight attendant was killed and more than 60 persons injured when part of the roof of an Aloha Airlines Boeing 737 tore off during a flight from Hilo (HEE'-loh) to Honolulu.

In 1993, the first "Take Our Daughters to Work Day," promoted by the New York-based Ms. Foundation, was held in an attempt to boost the self-esteem of girls by having them visit a parent's place of work. (The event was later expanded to include sons.)

Ten years ago: On Saddam Hussein's 66th birthday, delegates from inside and outside Iraq agreed to hold a nation-building meeting and fashion a temporary, post-Saddam government. The Soyuz space capsule carrying a U.S.-Russian space crew docked with the international space station.

Five years ago: The first tax rebates were direct-deposited into bank accounts from a $168 billion stimulus package. In a defiant appearance at the National Press Club in Washington, Democrat Barack Obama's longtime pastor, the Rev. Jeremiah Wright, said criticism surrounding his fiery sermons was an attack on black churches, and he rejected those who'd labeled him unpatriotic.

One year ago: Syria derided United Nations Secretary-General Ban Ki-moon as biased and called his comments "outrageous" after he blamed the regime for widespread cease-fire violations. Paticia Medina, 92, a British-born actress who became a leading lady in Hollywood films of the 1950s, died in Los Angeles.

Today's Birthdays: Pulitzer Prize-winning author Harper Lee is 87. Former Secretary of State James A. Baker III is 83. Director-actor Richard C. Sarafian is 83. Actress-singer Ann-Margret is 72. Actress Marcia Strassman is 65. Actor Paul Guilfoyle is 64. "Tonight Show" host Jay Leno is 63. Rock musician Chuck Leavell is 61. Actress Mary McDonnell is 60. Rock singer-musician Kim Gordon (Sonic Youth) is 60. Rapper Too Short is 47. Actress Simbi Khali is 42. Actress Bridget Moynahan is 42. Actor Chris Young is 42. Rapper Big Gipp is 40. Actor Jorge Garcia is 40. Actress Elisabeth Rohm is 40. Actress Penelope Cruz is 39. Actor Nate Richert is 35. Actress Jessica Alba is 32. Actor Harry Shum Jr. (TV: "Glee") is 31. Actress Jenna Ushkowitz (TV: "Glee") is 27. Actress Aleisha Allen is 22.

Thought for Today: "The world does not require so much to be informed as reminded." ? Hannah More, English religious writer (1745-1833).

(Above Advance for Use Sunday, April 28)

Copyright 2013, The Associated Press. All rights reserved.

Source: http://news.yahoo.com/today-history-050206767.html

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Saturday, April 27, 2013

ATD: Gates, Ballmer and Sean Parker join Zuckerberg's FWD.us lobby group

ATD: Gates, Ballmer and Sean Parker join Zuckerberg's FWD.us lobby group

Mark Zuckerberg showed he's more than just a social butterfly earlier this month, forming the tech-focused political lobby group FWD.us alongside some other big names in the industry. Now, according to AllThingsD, a few more heavy-hitters have signed up to offer their expertise, including Microsoft's Bill Gates and Steve Ballmer, Sean Parker and Intuit CEO Brad Smith. Not a bad crew to have on your side when technology issues are up for discussion, especially Ballmer -- he's notoriously good at getting his point across.

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Source: http://feeds.engadget.com/~r/weblogsinc/engadget/~3/hAeCyj-a5fk/

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The Engadget Show 43: Music with John Vanderslice, Black Milk, Dan Deacon, Pandora, Sub Pop and more!

These days, music and technology are inexorably linked -- from creation and recording, to distribution and discovery, it's hard to imagine a song reaching our ears that hasn't made its way through some electronic filter. Being the huge music nerds we are, we figured we'd use our April episode to explore the state of the music industry in 2013 and the roles technology has played in its successes and failings. This month, we start things off with a visit to Santa Cruz, where UCSC professor emeritus David Cope has spent decades developing classical music composing computer programs, work he began after one particularly bad bout with writer's block. We also stop by Seattle's Experience Music Project, where we speak to curator Jacob McMurray about the role technology has created in building a better music museum.

Next up, we've got a trio of interviews with artists who are using technology to very different ends in the creation and distribution of their music. John Vanderslice is the founder and proprietor of San Francisco's Tiny Telephone, one of the last remaining analog-only recording studios in a world increasingly dominated by Pro Tools. He's also a successful musician in his own right, who recently opted to eschew the traditional record label model for the release of his two new Kickstarter-backed albums. Hip-hop producer and emcee Black Milk, meanwhile, has taken to recording and producing recordings in his Dallas apartment. We discuss his crate digging, love of analog tools and the role of YouTube and Shazam in his production. And we meet up with indie electronic music Dan Deacon outside of LA's Natural History Museum to talk about his live rig and innovative iPhone app.

What about radio stations, you ask? We pay a visit to Jersey City's WFMU and Santa Monica's KCRW, two of the most prominent freeform stations in a space dominated Clear Channels and internet and satellite radio, to discuss the importance of human curation and embracing the same technology that has spelled the end of so many of their peers. We've also got interviews with Seattle's Sub Pop Records, music criticism site Pitchfork and California record store Amoeba, plus trips to music app developer Smule, internet radio pioneer Pandora and the legendary Moog factory. All that plus another installment of "John Roderick: Famous Prognosticator" and art by cartoonist Jim Rugg.

Oh, and we'd be remiss if we didn't remind you that today is the last day to vote for us in the Webby Awards! In the meantime, check out the full show, after the break.

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Source: http://www.engadget.com/2013/04/25/engadget-show-43/?utm_medium=feed&utm_source=Feed_Classic&utm_campaign=Engadget

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Friday, April 26, 2013

Gunman kills Hamelin politician then himself - The Local

A 74-year-old gunman killed a top official in the northern German town of Hamelin on Friday before shooting himself dead, police said.

"The perpetrator killed district administrator R?diger Butte and then killed himself," a police spokesman said. Officers were still at the scene on Friday afternoon, collecting evidence to support an investigation.

Shots were heard shortly after 10am in the city's main administrative building, where 63-year-old Butte was later found dead along with the body of his assailant.

The attacker was not identified. Police refused to comment on media speculation that the shooter was a gun fanatic but did say that the suspect was known to officers in the area. He used a heavy-calibered revolver to shoot Butte.

Butte was married with two adult children and five grandchildren, according to his profile on the district website. By Friday afternoon, his personal website had been taken off line.

Lower Saxony's Interior Minister Boris Pistorius said in a statement that Butte's murder had left him stunned. ?He will be missed by everyone. My thoughts go to his wife and children.?

He served as a police officer, rising through the ranks to become the head of the State Crime Investigations Office of Lower Saxony from 2001 to 2005. He had served as district administrator of Hamelin-Pyrmont, an elected office, since 2005.

The town is best known for the folk tale of the Pied Piper, later popularised by the Brothers Grimm.

Gun violence is rare in Germany, although major massacres in Erfurt in 2002 and Winnenden in 2009 made headlines around the world.

Gun crime, never high in Germany when compared with many other countries, dropped considerably over the past decade ? in 2000, police registered 19,400 crimes in which involved a firearm. By 2011, this figure stood at 11,700.

Of the 2011 statistics, 5,600 were shootings and 132 were incidents in which a gun was involved in a murder, manslaughter or assisted suicide investigation.

AFP/DPA/The Local/jcw

Source: http://www.thelocal.de/society/20130426-49387.html

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Workers pinned in Bangladesh rubble cry for rescue

A Bangladeshi woman survivor is lifted out of the rubble by rescuers at the site of a building that collapsed Wednesday in Savar, near Dhaka, Bangladesh, Thursday, April 25, 2013. By Thursday, the death toll reached at least 194 people as rescuers continued to search for injured and missing, after a huge section of an eight-story building that housed several garment factories splintered into a pile of concrete.(AP Photo/Kevin Frayer)

A Bangladeshi woman survivor is lifted out of the rubble by rescuers at the site of a building that collapsed Wednesday in Savar, near Dhaka, Bangladesh, Thursday, April 25, 2013. By Thursday, the death toll reached at least 194 people as rescuers continued to search for injured and missing, after a huge section of an eight-story building that housed several garment factories splintered into a pile of concrete.(AP Photo/Kevin Frayer)

In this image taken from AP video, garment worker Mohammad Altab moans to rescuers for help while trapped between concrete slabs and next to two corpses in a garment factory that collapsed Wednesday in Savar, near Dhaka, Bangladesh, Thursday, April 25, 2013. Deep cracks visible in the walls of the Bangladesh garment building had compelled police to order it evacuated a day before it collapsed, officials said Thursday. More than 200 people were killed when the eight-story building splintered into a pile of concrete because factories based there ignored the order and kept more than 2,000 people working. (AP Photo/AP video)

In this image taken from AP video, garment worker Mohammad Altab moans to rescuers for help while trapped between concrete slabs and next to two corpses in a garment factory that collapsed Wednesday in Savar, near Dhaka, Bangladesh, Thursday, April 25, 2013. Deep cracks visible in the walls of the Bangladesh garment building had compelled police to order it evacuated a day before it collapsed, officials said Thursday. More than 200 people were killed when the eight-story building splintered into a pile of concrete because factories based there ignored the order and kept more than 2,000 people working. (AP Photo/AP video)

Bangladeshi people gather as rescuers look for survivors and victims at the site of a building that collapsed Wednesday in Savar, near Dhaka, Bangladesh,Thursday, April 25, 2013. By Thursday, the death toll reached at least 194 people as rescuers continued to search for injured and missing, after a huge section of an eight-story building that housed several garment factories splintered into a pile of concrete. (AP Photo/A.M.Ahad)

Relatives cry as rescuers look for survivors and victims at the site of a building that collapsed Wednesday in Savar, near Dhaka, Bangladesh,Thursday, April 25, 2013. By Thursday, the death toll reached at least 194 people as rescuers continued to search for injured and missing, after a huge section of an eight-story building that housed several garment factories splintered into a pile of concrete on Wednesday. (AP Photo/A.M.Ahad)

SAVAR, Bangladesh (AP) ? "Save us, brother. I beg you, brother," Mohammad Altab moaned to the rescuers who could not help him. He had been trapped for more than 24 hours, pinned between slabs of concrete in the ruins of the garment factory building where he worked.

"I want to live," he pleaded, his eyes glistening with tears as he spoke of his two young children. "It's so painful here."

Altab should not have been in the building when it collapsed Wednesday, killing at least 238 people.

No one should have.

After seeing deep cracks in the walls of the building on Tuesday, police had ordered it evacuated. But officials at the garment factories operating inside ignored the order and kept more than 2,000 people working, authorities said.

The disaster in Savar, an industrial suburb of Dhaka, the capital city, is the worst ever for Bangladesh's booming and powerful garment industry, surpassing a fire five months ago that killed 112 people and brought widespread pledges to improve the country's worker-safety standards.

Instead, very little has changed in Bangladesh, where wages, among the lowest in the world, have made it a magnet for numerous global brands. Companies operating in the collapsed building say their customers included retail giants such as Wal-Mart, Dress Barn and Britain's Primark.

On Thursday, hundreds of rescuers, some crawling through the maze of rubble in search of survivors and corpses, spent a second day working amid the cries of the trapped and the wails of workers' relatives gathered outside the Rana Plaza building, which housed numerous garment factories and a handful of other companies.

Rescuers on Thursday evening found 40 survivors trapped in a room on the fourth floor. Twelve were soon freed, and crews worked to get the others out safely, said Brig. Gen. Mohammed Siddiqul Alam Shikder, who is overseeing rescue operations. Crowds at the scene burst into applause as survivors were brought out, although no other details were immediately available.

An Associated Press cameraman who went into the rubble Thursday morning with rescue workers spoke briefly to Atlab, the man who pleaded to be saved. But the team was unable to free Atlab, who was trapped next to two corpses.

From deep inside the rubble, another survivor could be heard weeping as he called for help.

"We want to live, brother! It's hard to remain alive here. It would have been better to die than enduring such pain to live on. We want to live! Please save us," the man cried. It was not immediately clear if he or Atlab were among those later rescued.

After the cracks were reported, managers of a bank that had an office in the building evacuated their employees. The garment factories, though, kept working, ignoring the instructions of the local industrial police, said Mostafizur Rahman, a director of that police force.

Abdur Rahim, who worked on the fifth floor, said he and his co-workers had gone inside Wednesday morning despite seeing the cracks. He said a factory manager had assured people it was safe.

About an hour later, the building collapsed, and the next thing Rahim remembered was regaining consciousness outside.

Officials said they had made it very clear that the building needed to be evacuated.

The Bangladesh Garment Manufacturers and Exporters Association had also asked the factories to suspend their work.

"After we got the crack reports, we asked them to suspend work until further examination, but they did not pay heed," said Atiqul Islam, the group's president.

As crews bored deeper into the wreckage, the odor of decaying bodies wafted through the building. Bangladesh's junior minister for home affairs, Shamsul Haque, said 2,000 people had been rescued.

Maj. Gen. Chowdhury Hasan Suhrawardy, a top military officer in the Savar area, told reporters that search and rescue operations would continue for at least three days after the collapse.

"We know a human being can survive for up to 72 hours in this situation. So our efforts will continue non-stop," he said.

Meanwhile, thousands of workers from the hundreds of garment factories across the Savar industrial zone took to the streets to protest the collapse and poor safety standards.

Shikder said the death toll had reached 238 by Thursday night. The garment manufacturers' group said the factories in the building employed 3,122 workers, but it was not clear how many were inside it when it collapsed.

Dozens of bodies, their faces covered, were laid outside a school building so relatives could identify them. Thousands gathered outside the building, waiting for news. TV reports said hundreds of protesters clashed with police in Dhaka and the nearby industrial zone of Ashulia. It was not immediately clear if there were any injuries in those clashes.

After the November fire at the Tazreen Fashions Ltd. factory, there were repeated calls for improved safety standards by labor activists, manufacturers, the government and major retailers, but little progress.

The building collapse highlighted the dangers that workers still face. Bangladesh has about 4,000 garment factories and exports clothes to leading Western retailers, and industry leaders hold great influence in the South Asian nation.

Its garment industry was the third largest in the world in 2011, after China and Italy. It has grown rapidly in the past decade, a boom fueled by Bangladesh's exceptionally low labor costs. The country's minimum wage is now the equivalent of about $38 a month.

Officials said soon after the collapse that numerous construction regulations had been violated.

Abdul Halim, an official with Savar's engineering department, said the owner of Rana Plaza was originally allowed to construct a five-story building but added another three stories illegally.

On a visit to the site, Home Minister Muhiuddin Khan Alamgir told reporters the building had violated construction codes and that "the culprits would be punished." Local police chief Mohammed Asaduzzaman said police and the government's Capital Development Authority have filed separate cases of negligence against the building's owner.

But on the streets of Dhaka, many believe the owners of the building and the factories will ultimately walk free.

"Was anyone punished earlier? Was the owner of Tazreen Fashions arrested? They are powerful people, they run the country," said Farid Ahmed, an insurance company official.

The Tazreen factory that burned in November lacked emergency exits, and its owner said only three floors of the eight-story building were legally built. Surviving employees said gates had been locked and managers had told them to go back to work after the fire alarm sounded.

Habibur Rahman, police superintendent of the Dhaka district, identified the owner of the collapsed building as Mohammed Sohel Rana, a local leader of ruling Awami League's youth front. Rahman said police were also looking for the owners of the garment factories.

Among the garment makers in the building were Phantom Apparels, Phantom Tac, Ether Tex, New Wave Style and New Wave Bottoms. Altogether, they produced several million shirts, pants and other garments a year.

The New Wave companies, according to their website, make clothing for major brands including North American retailers The Children's Place and Dress Barn, Britain's Primark, Spain's Mango and Italy's Benetton. Ether Tex said Wal-Mart, the world's biggest retailer, was one of its customers.

Wal-Mart said none of its clothing had been authorized to be made in the facility, but it is investigating whether there was any unauthorized production.

The Cato Corp., which sells moderately priced women's and girls' clothing, said that New Wave Bottoms was one of its vendors, but that it had no production with them at the time of the collapse.

Primark acknowledged it was using a factory in Rana Plaza, but many other retailers distanced themselves from the disaster, saying they were not involved with the factories at the time of the collapse or had not recently ordered garments from them.

Benetton said in an email to the AP that people involved in the collapse were not Benetton suppliers. Mango said it had only discussed production of a test sample of clothing with one of the factories.

U.S. State Department spokesman Patrick Ventrell said the collapse underscored the "urgent need" for the Bangladesh government, as well as the factory owners, buyers and labor groups, to improve working conditions in the country.

Highlighting failings in the patchwork system that retailers use to audit factories, two of Rana Plaza's garment companies had passed inspections by a major European group that does factory audits in developing countries. But the Business Social Compliance Initiative, which represents hundreds of companies and audited the Phantom Apparels and New Wave Style factories, said its standards focus more on labor issues than building standards.

Human Rights Watch says Bangladesh's Ministry of Labor has only 18 inspectors to monitor the more than 100,000 garment factories in the sprawling Dhaka district, where much of the nation's garment industry is located.

John Sifton, the group's Asia advocacy director, also noted none of the factories in the Rana Plaza were unionized, and had they had been, workers would have been in a better position to refuse to enter the building on Wednesday.

"Unionizing is Bangladesh remains incredibly difficult and dangerous," he said.

___

Associated Press Writers Muneeza Naqvi and Tim Sullivan in New Delhi, Stephen Wright in Bangkok, Kay Johnson in Mumbai, Matthew Pennington in Washington and AP Retail Writer Anne D'Innocenzio in New York contributed to this report.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2013-04-25-AS-Bangladesh-Building-Collapse/id-c7d432b6976241d5b2410a8304603e9b

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Former first lady Laura Bush shares tour of new Bush Center (cbsnews)

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Thursday, April 25, 2013

Jim Hoft's Breaking Bombshell of the Day: Victim of Terrorism Visited by Michelle Obama! (Little green footballs)

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Ban on strapless dresses for prom angers N.J. parents

By Victoria Cavaliere

(Reuters) - A New Jersey principal's ban on strapless dresses at a junior high school dance because they would be "distracting" to boys has enraged parents, who called on Tuesday for its reversal on the grounds it violates their daughters' constitutional rights.

The dress code shreds the 14th Amendment right to equal protection since girls for the past six years have been wearing sleeveless fashions to the dance at Readington Middle School in Readington Township, New Jersey, said parent Charlotte Nijenhuis.

Parents petitioned the school board on Tuesday to overturn the policy before the June 12th dance.

The school's principal, Sharon Moffat, said in a letter last month that a "dress with straps" was the only style that would be allowed.

Nijenhuis said she called Moffat to ask why strapless dresses had been forbidden. "She told me, ?It is because it's distracting to boys and inappropriate','" Nijenhuis said.

Moffat did not respond to a Reuters request for comment.

Another parent, Michelle D'Amico, said she was "livid" that her 14-year-old daughter was being prevented from wearing the same strapless dress that her older daughter had worn six years ago. "It's completely unjust," D'Amico said.

The Readington Township School District said in a statement on Tuesday that it "has a policy regarding dress code which is being universally applied to the school day and school events. We regret that a small number of families are upset by this and we welcome their input and communication."

At least one student, Claudine Nijenhuis, 14, said she planned to defy the ban and press her right to bare arms.

"Basically by saying 'it distracts the boys' you're also saying that it is our fault on how they control their own behavior," the teenager wrote in a letter to the principal. "I will still be attending the dinner dance function, but I will also be wearing a dress with no straps."

(Editing by Barbara Goldberg)

Source: http://news.yahoo.com/jersey-parents-demand-girls-bare-arm-strapless-dresses-022245280.html

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Wednesday, April 24, 2013

Italy president names center-left's Letta as new premier

By Barry Moody and Paolo Biondi

ROME (Reuters) - Italian President Giorgio Napolitano on Wednesday asked center-left politician Enrico Letta to form a new government, signaling the end of a damaging two-month stalemate since elections in the euro zone's third largest economy in February.

Letta, from the Democratic Party (PD), said he would start talks to form a broad-based coalition on Thursday. It is likely to go to parliament for a vote of confidence by early next week.

The prime minister designate is expected to select a group of ministers, likely to be a mixture of politicians and technocrats, under the guidance of Napolitano, whose own unprecedented re-election last weekend opened the way for an end to the crisis.

The new government will be backed primarily by Letta's center-left and the center-right People of Freedom party (PDL) led by Silvio Berlusconi, which had previously failed to reach a deal following inconclusive elections two months ago.

Rivalries between the parties as well as rifts within the PD, which fell short of a viable parliamentary majority in February's vote, could still block an accord. But formation of a government after such a long impasse would signal that Italy is finally ready to make a start on much-needed reforms.

Accepting his mandate, Letta said he would not form a government "at all costs", warning that the warring parties must make compromises or he would withdraw.

He said Italy faced an untenable situation and the government must provide answers on jobs, poverty and the crisis facing small businesses in a recession that now matches the longest since World War II.

European Union economic policies had been too focused on austerity instead of growth, he said, and Italy's parliamentary system must be reformed together with the widely criticized electoral law that has virtually guaranteed stalemate.

The bespectacled and balding Letta is an urbane moderate who speaks fluent English and at 46 would be one of Italy's youngest prime ministers, representing a generational change from the era of Berlusconi and outgoing Prime Minister Mario Monti.

A staunch pro-European and a member of the now-defunct Christian Democrat party in his youth, he is likely to be welcomed by foreign governments and markets and can also work with the center-right.

He is the nephew of Berlusconi's longtime chief of staff, Gianni Letta, and has numerous political friends on all sides of parliament, which could help ease the fractious climate since the election.

MARKET RELIEF

As Letta met close aides, the names being circulated as likely future ministers suggested a government broadly in line with Monti's outgoing technocrat administration but including senior politicians such as PDL party secretary Angelino Alfano.

Bank of Italy director general Fabrizio Saccomanni was seen as a possible economy minister and Enrico Giovannini, head of statistics agency ISTAT, may take over the industry ministry. Monti himself could return as foreign minister, helping to maintain the international contacts he cultivated as premier.

Investors had already reacted with relief to the prospect of an end to the intractable crisis, with Italy's two-year borrowing costs on Wednesday tumbling to their lowest level since the start of European monetary union in 1999.

However, the country's problems are not over, with significant differences remaining between left and right over economic policy and the center-left in disarray after letting slip an election it had once seemed sure to win.

These difficulties were put into sharp focus even before Letta was chosen, when Renato Brunetta, a senior member of Berlusconi's PDL party, said they would only support a government committed to repealing, and refunding, a housing tax introduced by Monti.

The center-left agrees only to a partial reduction of the tax and many economists say cuts in the levy would leave a gaping hole in Italy's public accounts.

Letta will also have to make sure he has his own party behind him. Factional infighting forced Pier Luigi Bersani to resign as party leader last week and there is significant internal opposition to any accord with Berlusconi.

Matteo Renzi, the ambitious young mayor of Florence seen as a potential leader of the center-left, could also prove a difficult partner to integrate.

Berlusconi gave a firm promise to Napolitano that he would support a coalition government in which his party shared power with the PD but favorable opinion polls may tempt him at some point to seek new elections.

Napolitano, who reluctantly agreed to serve another term as president, has made clear, however, that he will not accept endless squabbling between the parties and has threatened to resign if they do not unite behind economic and constitutional reforms.

(Additional reporting by James Mackenzie and Steve Scherer; Editing by Giles Elgood)

Source: http://news.yahoo.com/italy-president-set-announce-choice-prime-minister-054722232.html

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Universality of circular polarization in star- and planet-forming regions: Implications for the origin of homochirality of life

Apr. 23, 2013 ? A research team with Jungmi KWON (GUAS/NAOJ) has performed deep imaging linear and circular polarimetry of the 'Cat's Paw Nebula' (NGC 6334) located in the constellation Scorpius, successfully detecting high degrees of circular polarization (CP) of as much as 22% in NGC 6334. The detected CP degree is the highest ever observed.

In addition, the team has presented the first systematic survey of a combination of linear and circular polarimetry in nine star- and planet-forming regions. As the results of statistical analysis of observations of various star-forming regions, CPs were detected in nine star- and planet-forming regions. Putting it differently, it can be said that CP is a universal feature of star- and planet-forming regions. The team's findings enable us to obtain information about magnetic fields of circumstellar structures around protostars, which is difficult to obtain using existing methods.

There is a hypothesis that large CP causes homochirality of amino acids and that left-handed amino acids come from outer space. The team's findings imply an extraterrestrial origin of homochirality of life, from the universality of CP detected in star- and planet-forming regions.

This research is part of an ongoing survey project of wide-field near-infrared (JHKs) imaging polarimetry for star-forming regions (PI: Motohide TAMURA, University of Tokyo/NAOJ). Doctoral student Jungmi KWON, who is contributing to the project, led this research with nine international researchers from Japan and the United Kingdom. The team's findings were published in the Astrophysical Journal Letters on March 1, 2013.

Notes:

(1) An instrument used for observations is the IRSF (InfraRed Survey Facility), a 1.4 m telescope with a built-in SIRPOL imaging polarimeter at an elevation of about 1761 meters at the South African Astronomical Observatory in Sutherland, South Africa. The field of view (~ 8 x 8 arcmin2) enables us to observe a wide field in the three (JHKs) bands simultaneously.

(2) The 'Cat's Paw Nebula' is a star- and planet-forming region located in the constellation Scorpius. It is approximately 5,500 light years distant from the Earth.

(3) A chiral molecule (from the Greek word for 'hand') is a molecule that cannot be superimposed on its own mirror image. A hand is chiral in the sense that the mirror image of a left hand is a right hand, and the two hands cannot be superimposed. All the vital biomolecules of life possess the same handedness (left-handedness); this is called homochirality.

Research Background

What is the origin of life on Earth? Where did life on Earth come from? Research into star and planet formation throws new light on on these questions and arouses public curiosity.

The Cat's Paw Nebula is located in the galactic plane of our Milky Way Galaxy, and it is 5,500 light years away from the Earth. The nebula is known to be one of the most active star-forming regions in the Milky Way Galaxy, containing many young stars of the Sun's mass, born about one million years ago. Even though tens of thousands of young stars are also embedded in the Cat's Paw Nebula, the stars cannot be seen in optical wavelengths because they are buried inside the optically thick (molecular or dark) clouds of gas and dust.

For this reason, our research team used near-infrared to observe the site where stars and planets are being born. Infrared light enables us to look at regions that are heavily obscured in the optical wavelengths. This means that we can expect to hear the story about the trip photons in the infrared make to observers on the face of the Earth from heavenly bodies in space in the same way as photons from stars experience.

Furthermore, a unique characteristic of light called 'polarimetry' enables us not only to obtain information of the intensity of near-infrared from illuminating sources, but also that of (linearly or circularly) polarized light. The properties of polarized light, an important tool in astronomy, have even been the focus of astrobiology -- the study of life in the universe.

Origin-of-life theories often ignore the homochirality problem, even though the question is critical to the origin of life. Scientists hypothesized that the enantiomeric excess of L-amino acids in extraterrestrial sources could be due to circular polarization, which selectively destroys the opposite-handed enantiomer. In previous studies in 1998, an extended CP region was reported in the Orion nebula. It was the only example to show extended and high CP, and there is no observation to study the universality of CP obtained from space, not in laboratories on Earth. The reason is that there were no instruments available to detect any circularly polarized light with wide field of view and high sensitivity.

Results from near-infrared polarimetric observations

The history of star and planet formation and the origin of life are still a mystery, and the team with Jungmi KWON who belongs to GUAS, NAOJ, and JSPS is involved in working out the puzzle. To solve the puzzle, the team used the IRSF 1.4 m telescope with SIRPOL imaging polarimeter at the South African Astronomical Observatory in Sutherland (at an elevation of about 1761 meters), which is the one of the coldest places in South Africa. The telescope and instrument are operated by Nagoya University, Kyoto University, and NAOJ. SIRPOL is an instrument developed by our group; it enables us to obtain information of circularly polarized light as well as linearly polarized light. It also enables wide-field (~ 8 x 8 arcmin square in the sky = ~ 1/4 diameter of the moon) imaging polarimetry, which is a decidedly broader scope than other existing instruments. In other words, IRSF/SIRPOL has one of the highest performances in the present for (linearly and/or circularly) polarized light in the near-infrared toward a wide field of view of the sky.

The observations caught scattered lights of dust grains, as material of reflection nebulae around young massive stars, from an illuminating source. The data show the following features: (1) infrared reflection nebula around the central source, (2) hourglass-shaped outflow, (3) quadrupolar patterns of CP extended to the outside of circumstellar structures broader than the outflow, (4) the highest CP degree (22%) so far observed in star-forming regions, and (5) the maximum CP extents (about 600 times of the size of our solar system).

The young massive star that is the illuminating source of the reflected bipolar nebula is located around the center of each side of the nebula. Even though it is obstructed by optically thick gas and disk in near-infrared, it can be observed in mid-infrared (longer wavelength). Our linear polarimetry data that enable us to know the size of the reflection nebulae as well as the position of the central source also indicate the existence and location of the illuminating source in this bipolar nebula.

The team's findings toward the massive star-forming region NGC 6334-V in the Cat's Paw Nebula suggest a unique characteristic of light named CP is extended over more than the Orion nebula that was the largest CP region ever detected until the team found CP in the Cat's Paw Nebula. Furthermore, the team firstly detected very clear quadrupolar pattern with the highest CP degree. This is a scientific breakthrough in CP observations of star-forming regions.

The team also performed survey observations of polarized light in various star-forming regions, and the researchers successfully detected CP in nine star- and planet-forming regions such as Orion, Taurus, Chamaeleon, etc. There are only three regions to show large CP greater than 2 % in the previous studies of CP in star-forming regions. Until now, since the number of CP observations and successful detection was too small, statistical debate on the characteristic of CP in star-forming regions was not reached. The team's findings present CP is greater than 2 % in all intermediate and massive star-forming regions, and suggest massive star-forming regions with large luminosities tend to large and extended CP. These are the first systematic results obtained from the infrared circular polarization survey with the unique instrument.

A comparison with observations and models

The team not only performed observations but also three-dimensional Monte Carlo simulations. The simulations reveal the mechanism of large CP (22%) shown in observations. The idea is that photons are released from a central star, and we trace and estimate the interaction between the light and surrounding structures numerically. In existing mechanisms of CP, even though multiple scattering was mainly considered as the mechanism to generate CP, it cannot generate large CP over 1 %.

The team's findings using the three-dimensional Monte Carlo simulations suggest (1) light from the illuminating source of reflection nebulae is scattered by circumstellar structures, (2) the scattered light is circularly polarized by dust grains aligned with the magnetic field (dichroic extinction). It successfully reproduces large CP such as that over 20% as well as the quadrupolar patterns of CP.

Intimation of the relationship between huge CP in massive star-forming regions and life in the Solar system

Life on Earth is made of "left-handed amino acids (L-amino acids)." The question of why organisms on Earth consist of L-amino acids instead of D-amino acids or consist of D-sugar instead of L-sugar is still an unresolved riddle. In other words, a major mystery of life on Earth is that organisms are exclusively made up of left-handed amino acids. Therefore, the effort to solve this problem is one of the biggest in research into the origins of life, a subject that remains enveloped in mystery.

What kind of mechanism causes the selection of all L-amino acids? One of the mainstream hypotheses today is this: photolysis of one enantiomer of a racemic amino acid with circularly polarized light, transfer of chirality from enantioenriched amino acids to proteinogenic amino acids, and aqueous amplification of one enantiomer with preferential dissolution. Thus, how the circularly polarized light physically works is important in determining the hypothesis of an extraterrestrial origin of homochirality or the origin of abiogenesis on Earth. For the hypothesis of an extraterrestrial origin, CP of synchrotron radiation in neutron stars has emerged as a candidate for extraterrestrial sources. Recently, CP detected in the Orion nebula has been mentioned as the strongest candidate, as originally suggested by Jeremy Bailey at The University of New South Wales and his collaborators. On the basis of such a hypothesis, the scenario below can be conjectured.

"Above all, organic material such as amino acids is made in a molecular cloud. Next, any initial surplus of L-amino acids is initiated by CP. The L-amino acids are transferred to parent meteorites or comets when the solar system is formed, and they are eventually transported to Earth. In the prebiotic sea, a small amount of surplus of L-amino acids is amplified by an amplifying action such as a Soai response. At the end of such a process, life is born with homochirality of amino acids."

In connection with the team's findings, the suggested scenario is that (1) the solar system is formed in massive star-forming regions such as the Cat's Paw Nebula and Orion nebula, (2) the solar system is swallowed up in the huge CP region, (3) amino acids, completely affected by one side of the CP region, are biased towards L-amino acids, and then (4) the L-amino acids are finally carried to Earth with meteorites, comets, etc. However, since debates continue about transmutation of meteorites in the hypothesis of an extraterrestrial origin, improved observations, experiments, and theories are being sought.

Summary Including Current and Future Positions

The research team successfully detected high degrees of CP (22%) in the nebula including young stars. The detected CP degree is the highest among CPs reported in star-forming regions. The team also shed light on the mechanism of CP. From this, CP has become a new tool with which to obtain information about the effects of magnetic fields and circumstellar structures that can affect the process of star and cluster formation. Furthermore, both the CP detection that is not only higher but also broader than in the Orion nebula and the universality of CP in various star-forming regions imply that Orion is not the only candidate for CP as the extraterrestrial origin of homochirality on life. Putting it differently, in star- and planet-forming regions, CP may be a common feature. These findings are among the latest knowledge obtained using the unique method called 'wide-field near-infrared imaging polarimetry observations'.

'Astrobiology' that builds on technological and scientific capability is expected to open doorways to new knowledge in many fields, with the progress of extrasolar planet observations and solar system research. Hereafter, the research team will continue its wide-field CP survey of star- and planet-forming regions and make new attempts to conduct high-resolution observations of CP. The team's findings using polarized light toward star- and planet-forming regions are expected to provide the basis for another ongoing project, the Subaru Strategic Exploration of Exoplanets and Disks with HiCIAO/AO188 (SEEDS).

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Story Source:

The above story is reprinted from materials provided by National Astronomical Observatory of Japan.

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


Journal Reference:

  1. Jungmi Kwon, Motohide Tamura, Phil W. Lucas, Jun Hashimoto, Nobuhiko Kusakabe, Ryo Kandori, Yasushi Nakajima, Takahiro Nagayama, Tetsuya Nagata, James H. Hough. Near-infrared Circular Polarization Images of NGC 6334-V. The Astrophysical Journal, 2013; 765 (1): L6 DOI: 10.1088/2041-8205/765/1/L6

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://www.sciencedaily.com/releases/2013/04/130423090924.htm

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News Corp settles shareholder lawsuit

(Reuters) - News Corp on Monday said it recovered a $139 million in insurance proceeds in a settlement with shareholders over the board of directors' actions related to the company's phone hacking scandal and its acquisition of Shine studios.

The company said the money would come from insurance policies held by members of the board who were the defendants in the suits.

News Corp also said it would adopt enhanced corporate governance procedures, which would stay in place after the company's pending split later this year.

The agreement said the settlement is not an admission of wrong doing by News Corp.

"We are pleased to have resolved this matter," News Corp said in a statement.

"The agreement reflects the important steps News Corporation has taken over the last year to strengthen our corporate governance and compliance structure and we have committed to building on those efforts going forward."

Plaintiffs, including Amalgamated Bank and the New Orleans Employees' Retirement System, first sued in March 2011 over News Corp's acquisition of Shine Group Ltd, a company owned by Chairman Rupert Murdoch's daughter.

They amended the lawsuit in July 2011 to add claims related to the phone hacking scandal, which led News Corp shut down its British newspaper News of the World.

"We are proud of this historic settlement, which continues the 20 year history of Amalgamated Bank encouraging corporate reform and improved corporate governance." Edward Grebow, president & CEO of Amalgamated Bank, said in a statement.

Central Laborers Pension Fund and the City of New Orleans Employees' Retirement System (NOMERS)Chairman Edgar Chase said in statement, "We are proud of the meaningful role that we and our counsel played in the Company's continuing efforts to strengthen its governance on behalf of our beneficiaries in achieving this recovery and further improving corporate governance practices at News Corporation."

The agreement represents one of the largest derivative settlements in Delaware.

(Reporting by Ben Berkowitz; Editing by Gerald E. McCormick and Jeffrey Benkoe and Theodore d'Afflisio)

Source: http://news.yahoo.com/news-corp-139-million-shareholder-lawsuit-settlement-123202454--finance.html

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Los Preps Rap Coronation On Becoming King Mixtape

'There's a lot of pressure whenever you make an all-original project because you can't cheat,' Los tells Mixtape Daily.
By Rob Markman, with reporting by Ade Mangum

Source: http://www.mtv.com/news/articles/1706148/los-mixtape-becoming-king.jhtml

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Tuesday, April 23, 2013

Same protein that fires up cancer-promoting Erk also blocks its activation

Monday, April 22, 2013

A protein which is intimately involved in cancer-promoting cell signaling also keeps a key component of the signaling pathway tied down and inactive, a team led by scientists from The University of Texas MD Anderson Cancer Center reports this week in Nature Structural Molecular Biology.

Shc, pronounced "schick," plays a key role in activating signals which lead to cell proliferation (and cancer) when cells are stimulated, however it unexpectedly turns out to be a tumor-suppressor, keeping Erk under wraps when a cell is less active, said senior author John Ladbury, Ph.D., professor in MD Anderson's Department of Biochemistry and Molecular Biology.

"Shc is a checkpoint to prevent out of control cell growth, binding to Erk when a cell is not being stimulated by growth factors," Ladbury said. "Otherwise, the lower-level background signaling that's always present in a cell would be uncontrolled."

Keeping Erk in check while the cell idles

Overexpression of Erk occurs in many types of cancer, including ovarian and prostate cancer and Hodgkin lymphoma, so cellular control of its activity is important.

In the absence of external stimulation by growth factors, cells remain active but lower levels of cell signaling occur, which Ladbury compares to a car idling, ready to roll. Under these conditions control mechanisms are in place to prevent the cell kicking into gear. Shc turns out to be one of these controllers.

"We're essentially looking at the cell in a resting, but ready, state," Ladbury said. "I would argue that's probably more like a cell behaves in tissue, it's not normally getting a slug of growth factors as is often the way when we investigate signaling in experiments in the lab. There's still a lot going on in the cell, basically background activity."

These findings point to a number of therapeutic possibilities, including the measurement of Shc concentration levels as a diagnostic tool and of finding small molecule drugs that block growth-factor signaling to Shc, keeping it bound to Erk, Ladbury noted.

Growth factors provide double boost for Erk

When the appropriate growth factor receptor is stimulated Erk is activated in the MAP Kinase pathway. It dives into the cell nucleus and turns on a variety of genes, actions that contribute to cancer proliferation, blood vessel production and metastasis when signaling is out of control.

When receptor tyrosine kinases on the cell surface connect with growth factors, they normally send a signal via Shc that sets off a chain of actions leading to Erk activation. Ladbury and colleagues looked at Shc's connections to epidermal growth factor receptor (EGFR) signaling.

The team found in mammalian cell lines that:

  • Under non-stimulated conditions Shc binds to Erk in the cell cytoplasm at binding sites that are unique on both proteins.
  • Stimulation via EGFR reduces this connection, but not by competing with Shc at the Shc-Erk binding site.
  • Instead, on stimulation from outside the cells, EGFR adds phosphate groups to itself at specific sites. One of these forms a binding for Shc, which distorts the protein's shape, making it impossible for Erk to bind.
  • Overexpression of Shc decreases the amount of activated Erk, because Shc mops up free Erk molecules.
  • Depleting Shc expression with short hairpin RNA resulted in higher levels of activated Erk.
  • When separated from Shc, Erk moves into the nucleus and activates genes even when the cell is not receiving a stimulus. Thus without the controlling influence of Shc, Erk can run riot in the cell giving rise to unrestrained cell reproduction.

Shc-Erk connection confirmed

Ladbury and colleagues then tested their results in the C.Elegans, a worm model frequently employed in biological research. Both Shc and Erk are greatly similar between humans and the worms.

Experiments showed that Shc blocks Erk function by sequestering it away from the Ras-Raf-Mek MAPK pathway in the worms. Without the Shc-Erk connection, the MAPK pathway is activated, causing excessive Erk activation.

EGFR stimulation not only sets off the normal activation of Erk via Shc and the MAPK pathway, Ladbury said, but also frees Erk for greater availability for activation by breaking the tie to Shc.

Co-authors with Ladbury are first author Kin Man Suen and Chi-Chuan Lin, Ph.D., Fernando Melo, Ph.D., Zamal Ahmed, Ph.D., and Stefan Arold, Ph.D., all of MD Anderson's Department of Biochemistry and Molecular Biology; Roger George, Ph.D., of the London Research Institute of Cancer Research UK; Eleanor Biggs, of the University of Bath, Bath, UK; and Melanie Drake and Swathi Arur, Ph.D., of MD Anderson's Department of Genetics.

Suen is a graduate student in The University of Texas Graduate School of Biomedical Sciences, which is run jointly by MD Anderson and The University of Texas Health Science Center at Houston. Ladbury and Arold also are affiliated with the Center for Biomolecular Structure and Function at MD Anderson.

###

University of Texas M. D. Anderson Cancer Center: http://www.mdanderson.org

Thanks to University of Texas M. D. Anderson Cancer Center for this article.

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Source: http://www.labspaces.net/127839/Same_protein_that_fires_up_cancer_promoting_Erk_also_blocks_its_activation

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