SAN FRANCISCO ? Silicon Valley entrepreneur-turned-venture capitalist Marc Andreessen and his partners have raised another $1.5 billion to invest in technology startups as they prepare to profit from a previous bet on Internet social network Facebook.
The fundraising announced Tuesday serves as further validation of the success that Andreessen has enjoyed since he started his own venture capital firm in mid-2009. The Menlo Park, Calif., firm, Andreessen Horowitz, has invested in about 90 companies since then. The portfolio includes an unspecified stake in Facebook, which is expected to file its plans for a long-awaited initial public offering of stock as early as Wednesday.
Those IPO documents may divulge the holdings of Andreessen Horowitz, if it is among Facebook's biggest stockholders. Before co-founding his venture capital firm, Andreessen also personally invested in Facebook and joined the company's board of directors in 2008.
Andreessen, 40, got rich as one of the Internet industry's first big stars during the 1990s. He helped change the way people used the Internet as part of a team that developed a graphical Web browser called Mosaic in the early 1990s. He went on to co-found Netscape Communications before he had turned 25. After losing its early lead in the Web browser market to Microsoft Corp. in a bruising battle, Netscape was sold to AOL for $10 billion in 1999.
With the latest infusion, Andreessen Horowitz has raised $2.7 billion since the firm's inception. The firm's other partners include Andreessen's longtime business partner, Ben Horowitz, and Jeff Jordan, former CEO of online restaurant reservation service OpenTable Inc.
"We are single-mindedly focused on partnering with the best innovators pursuing the biggest markets," Andreessen said in a statement.
Facebook, which started eight years ago in CEO Mark Zuckerberg's Harvard University dorm room, is expected to seek an IPO price that would value the company at $75 billion to $100 billion, according to The Wall Street Journal.
Andreessen Horowitz also was among the early investors in Zynga Inc., a maker of "FarmVille," "Words With Friends" and other games that are frequently played on Facebook's social network. Zynga's stock has received a lukewarm response since its Wall Street debut in December. Zynga's stock gained 10 cents to close at $10.49 on Tuesday, just slightly above its IPO price of $10.
Although it focuses on startups, Andreessen Horowitz has explored investing in older companies too. Last year, it was one of several firms discussing the possibility of buying a nearly 20 percent stake in long-slumping Internet company Yahoo Inc. There was even speculation that Andreessen might join Yahoo as an executive, an idea that he refuted in a posting on his personal blog in December.
Yahoo has since hired former PayPal executive Scott Thompson as its fourth CEO in less than five years.
LOS ANGELES ? When your dinner party guests include Brad Pitt, George Clooney, Kate Winslet and Glenn Close, and the whole affair is televised live, it can take months to plan the menu. That's why the team behind the Screen Actors Guild Awards began putting together the plate for Sunday's ceremony months ago.
It was still summer when show producer Kathy Connell and executive producer and director Jeff Margolis first sat down with chef Suzanne Goin of Los Angeles eatery Lucques with a tall order: Create a meal that is delicious at room temperature, looks beautiful on TV, is easy to eat and appeals to Hollywood tastes. Oh, and no poppy seeds, soups, spicy dishes, or piles of onions or garlic.
"It can't drip, stick in their teeth or be too heavy," Connell said. "We have to appease all palates."
The chef put together a plate of possibilities: slow-roasted salmon with yellow beets, lamb with couscous and spiced cauliflower and roasted root vegetables with quinoa. There was also a chopped chicken salad and another chicken dish with black beans.
To ensure the dishes are both tasty and TV-ready, Connell and Margolis, along with the SAG Awards Committee and the show's florist and art director, dined together at this summertime lunch on tables set to replicate those that will be in the Shrine Exposition Center during the ceremony. The pewter, crushed-silk tablecloths and white lilies you'll see on TV Sunday were also chosen months ago.
The diners discussed the look of the plate, the size of the portions and the vegetarian possibilities.
"We'd like the portions a little larger," Connell told the chef.
"And a little more sauce on the salmon," Margolis added.
Come Sunday, it's up to Goin to prepare 1,200 of the long-planned meals for the A-list audience.
Top Democrats have abdicated their leadership role and are ignoring the nation?s budget problems because they?re focused on their 2012 election campaigns, Alabama Republican Sen. Jeff Sessions told The Daily Caller.
?We?re heading towards the most predictable crisis in our history,? said Sessions, the top Republican on the Senate?s budget committee,??and we have no leadership.?
The Democrats will instead use their control of the Senate to make the GOP look bad, Sessions predicted.
?I doubt they?ll propose to raise the capital gains [rate] ? but they?ll talk about it and complain about it, and try to make it look like Gov. [Mitt] Romney did something wrong? by paying his capital-gains taxes properly, he told TheDC.
?They?ve made a calculation that they?ll lay the responsibilities on us to be the [budget] naysayers, the worriers and hand-wringers, and they?ll put on the bright robes of hope and progress,? Sessions warned.
President Barack Obama didn?t address the impending budget disaster in his State of the Union speech, and he?s ignoring it in his re-election campaign, observed Sessions, whose status as part of the GOP minority?prevents him from calling hearings or forcing votes.
Since Obama was inaugurated, Congress has approved $4 trillion worth of economic stimulus via deficit spending. In those three years the accumulated deficit has exceeded $15 trillion, equal to the entire annual value of the U.S. economy.
Economic growth has stalled, the nation?s credit rating has been downgraded, and millions of Baby Boomers have signed up for Social Security and Medicare.
Democratic Senate Majority Leader Harry Reid is also refusing to pass a budget, Sessions said, because that would force his members to vote on GOP proposals.
The Democratic Senate hasn?t produced a budget bill for the last three years, ensuring the budgets are assembled without the senators having to vote on amendments.
The leading Democrat on the budget committee, North Dakota Sen. Kent Conrad, has promised that the committee will, in fact, produce a budget for 2012.
But there?s no guarantee that any budget will be debated on the Senate floor, even though some Democratic senators are worried enough about the nation?s finances to push for a budget debate, Sessions explained.
?If Harry Reid really works it hard, he?s proven he can hold his members [in check], and he does not want to have a vote on this,? he said.
The budget-writing process is important, he insisted, because it would ?commit them to a plan for the future for America, and it shows just how much they want to raise taxes [and] increase spending, and how much the debt is going to increase.?
For example, in a Senate floor debate, ?you have 50 hours of full debate, and you can have an unlimited number of amendments, and it allows the minority party to bring forth their ideas [about] how to fix the nation,? he said.
The Democrats are avoiding budgetary issues because their political priorities are too unpopular to pass, he added. ?I think they know their [Senate] majority is endangered if they advocate openly and publicly and on the record, for items [they favor] that raise the debt and raise spending.?
The president also ignored the impending disaster in his Jan. 24 State of the Union speech, Sessions said.
?Every issue where he had a serious disagreement [with the public], he had some language saying he agreed with the American people, but then he would go on to stick by his regulatory and other [spending] plans? It was a craftily crafted speech,? Sessions quipped.
The Democrats? strategy of obfuscation is hard to understand, Sessions told TheDC. ?I can?t imagine it would be successful, because there was great momentum in the last election for a confrontation with our surging debt.?
In the October election, he added, ?the big spenders took a shellacking, I thought the administration and the Democratic Senate would respond to that.?
But the Democrats, he claimed, haven?t risen to the occasion.
This year, ?it appears their political strategy is that they?re going to talk about hope and not talk about realities. ? That is a deep failure of leadership.?
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NEW YORK (Reuters) ? Stock index futures pointed to a steady open on Wall Street on Friday, with futures for the S&P 500 up 0.02 percent, Dow Jones futures up 0.05 percent and Nasdaq 100 futures up 0.2 percent at 4 a.m. ET.
European stocks dipped in early trade following strong increases in the previous session, as gains sparked by the Federal Reserve's pledge of low interest rates gave way to worries about Portugal, seen as the potential next domino in the euro zone crisis, and uncertainty over Greek debt talks. (.EU)
The Federal Reserve's latest efforts to bolster the recovery with unprecedented policy tools will hurt the U.S. economy in the long run, a former member of Fed Chairman Ben Bernanke's inner circle suggested on Thursday.
3M Co's (MMM.N) board of directors are divided over whether to extend the contract of chief executive George Buckley once it expires in a month, the Wall Street Journal reported on Friday, citing a person familiar with the matter.
The economy likely grew at its fastest pace in nearly two years at the end of 2011, but a rebuilding of stocks by businesses and weak exports could be early warning signs of a slowdown in early 2012. U.S. gross domestic product is expected to have expanded at a 3.0 percent annual rate in the fourth quarter, according to a Reuters poll.
The yield on the benchmark U.S. Treasury note was steady in Asia on Friday, while the yield on five-year paper was slightly above a multi-decade low as investors awaited U.S. data later in the session that is likely to show the economy has picked up.
Richmond Federal Reserve Bank President Jeffrey Lacker said on Friday he voted against the central bank's decision this week to keep rates near zero until at least late 2014 because he believes rates will need to rise before then.
Juniper Networks (JNPR.N) and Riverbed Technologies (RVBD.O) disappointed investors with gloomy first quarter outlooks that were below expectations, raising fears that demand for companies that help manage Internet traffic may be weak for some time.
Cirrus Logic Inc (CRUS.O) forecast fourth-quarter revenue higher than analysts' estimates as the analog chipmaker expects to launch several new products during the period.
Delphi Automotive PLC (DLPH.N) reported a nearly four-fold increase in fourth-quarter earnings on stronger sales of vehicle electronics and engine systems in its first results since returning as a public company.
Sallie Mae (SLM.O), the largest U.S. student lender, raised its quarterly dividend and said its board authorized a $500 million share buyback program.
A Brazilian prosecutor plans to file criminal charges against Chevron Corp (CVX.N) and some of its local managers within weeks, adding the threat of prison sentences to an $11 billion civil lawsuit as punishment for a November offshore oil spill.
A month-long rally on Wall Street appears to be sputtering as stocks slipped on Thursday in what investors called a possible warning of weakness ahead. Weaker-than-expected home sales figures and a group of mixed earnings reports tempered the market's recent buying interest.
The Dow Jones industrial average (.DJI) was down 22.33 points, or 0.18 percent, at 12,734.63. The Standard & Poor's 500 Index (.SPX) was down 7.60 points, or 0.57 percent, at 1,318.45. The Nasdaq Composite Index (.IXIC) was down 13.03 points, or 0.46 percent, at 2,805.28.
(Reporting by Blaise Robinson; Editing by Helen Massy-Beresford)
Former Palm chief Jon Rubinstein has left Hewlett-Packard, having completed the 24-month commitment period he agreed to when HP acquired Palm. An HP spokesperson has confirmed the story, first reported by AllThingsD, in a brief statement: "Jon has fulfilled his commitment and we wish him well."
Rubinstein rose to fame as a hardware guru at NeXT, ultimately joining Apple after the company acquired NeXT in 1996. He was instrumental in developing the iMac and PowerMac desktops before spearheading the iPod project that would herald the company's business dominance. After retiring in 2006, he joined Palm to revitalize the flagging device maker's fortunes, developing the Palm Pre and WebOS software before being crowned as its CEO in 2009. A year later, Hewlett-Packard purchased the company for $1.2 billion: but just a year later, pulled the shutters down as Rubinstein was shifted (or "dumped") to a "product innovation role" within HP, where he saw out the last of his retention period before departing. In a terse comment to The Verge, the man himself has said that he's "going to take some well deserved time off," and after the last twelve months, we wouldn't blame him.
FRIDAY, Jan. 27 (HealthDay News) -- When a couple is trying to have a baby and can't, it can be emotionally and financially draining. But help may be available in an unexpected form: acupuncture.
Medical experts believe that this ancient therapy from China, which involves placing numerous thin needles at certain points in the body, can help improve fertility in both men and women.
"Acupuncture has been around for almost 3,000 years. It's safe and there are no bad side effects from it," explained Dr. Lisa Lilienfield, a family practice and pain management specialist at the Kaplan Center for Integrative Medicine in McLean, Va. "It may not be the only thing that is done in isolation to treat infertility, but it helps get the body primed and maximizes the potential effects of fertility treatments."
Dr. Jamie Grifo, director of the New York University Fertility Center and director of the division of reproductive endocrinology at the NYU Langone Medical Center in New York City, said that "it's not a panacea, but acupuncture does help some patients have better success."
"It's one non-traditional modality to help manage the stress of infertility, and it does improve pregnancy rates and quality of life in some people," he said.
In addition to relieving stress, Lilienfield said that acupuncture can help increase a woman's fertility by improving blood flow to the ovaries and uterus. This improved blood flow can help thicken the lining of the uterus, increasing the chances of conception.
It may also help correct problems with the body's neuroendocrine system. Acupuncture can help activate the brain to release hormones that will stimulate the ovaries, adrenal glands and other organs that are involved in reproduction, according to Lilienfield. Acupuncture's effect on the neuroendocrine system may also help infertile men by stimulating sperm production, she said.
Studies that have been done on acupuncture and fertility have had mixed results, with some showing benefits and others showing none. Grifo said the differing results may have something to do with the design of the studies. Two areas that appear to be more consistently helped by acupuncture treatments are in vitro fertilization and women who are infertile due to polycystic ovary syndrome.
Two studies -- one in Acupuncture in Medicine and the other in the Journal of Endocrinological Investigation -- found a benefit when acupuncture was used on the day an embryo was transferred into a woman's uterus.
The study from the Journal of Endocrinological Investigation also found that women with polycystic ovary syndrome and men who had infertility issues with no known cause also benefitted from acupuncture.
The actual treatment session involves placing very thin needles at specific points in the body. In Chinese medicine, these points are believed to be areas where a person's "qi" (pronounced chee), or life force, is blocked, according to the U.S. National Center for Complementary and Alternative Medicine. In Western medicine, it's believed that the needle placement may release the body's natural painkillers.
Acupuncture is commonly used to treat pain, such as back pain, headache and menstrual cramps, according to the center.
Lilienfield said that acupuncture treatment costs vary, depending on where someone lives and the training of the practitioner. In her center, a treatment costs about $135, and most people receive six to eight treatments for infertility, she said. Insurance reimbursement also varies, she noted, though many insurance companies will pay for acupuncture.
In general, someone younger than 35 is often advised to try to get pregnant for about a year before seeking treatment for infertility. "But, if you're anxious to get going, six months is a reasonable time to wait," Lilienfield said. And women older than 35 probably shouldn't wait more than six months, she added.
Grifo said he doesn't favor waiting that long to seek treatment. "If you are trying to get pregnant and struggling with it, you don't need to wait a year," he said. "And, if you're over 35, don't wait six months to get worked up if it's causing you distress."
More information
The U.S. National Center for Complementary and Alternative Medicine has more on acupuncture.
ANKARA, Turkey ? Turkey has marked the international Holocaust Remembrance Day by airing a French epic documentary about the Holocaust.
TRT television's documentary channel showed filmmaker Claude Lanzmann's "Shoah" late on Thursday, on the eve of the remembrance day.
The filmaker said this is the first time the film was broadcast on state television in a Muslim country.
The documentary was aired as part of a campaign to promote understanding between Jews and Muslims and to fight Holocaust denial.
In March, a Los Angeles-based Farsi satellite channel had also broadcast the 9-plus-hour documentary in Iran, where President Mahmoud Ahmadinejad has questioned historical accounts of the Holocaust.
Lanzmann worked for 11 years on the film, which was released in 1985.
BANGKOK ? Oil rose above $100 a barrel Thursday in Asia after the U.S. Federal Reserve said it would keep interest rates at record lows at least until 2014 to help jump-start the world's biggest economy.
Benchmark crude for March delivery was up 71 cents at $100.11 a barrel at midday Bangkok time in electronic trading on the New York Mercantile Exchange. The contract rose by 45 cents to finish at $99.40 per barrel in New York on Wednesday. At one point it was as high as $100.40.
Brent crude for March delivery was up 88 cents at $110.69 a barrel on the ICE Futures Exchange in London.
The U.S. central bank, which has kept its benchmark interest rate near zero for three years, said Wednesday that it doesn't plan to raise the rate before late 2014.
That caused the dollar to turn lower against major currencies, which makes dollar-priced oil less expensive for holders of other currencies.
"That would mean the U.S. dollar would continue to be cheap versus other currencies, and there is typically an inverse correlation between the value of the dollar and commodity pricing," said Victor Shum, an energy analyst at consultancy Purvin & Gertz in Singapore.
"So oil prices are supported by the Federal Reserve statement," he said.
But other analysts saw room for oil prices to fall.
Leaving rates low would encourage businesses and consumers to borrow money cheaply, boosting the economy and leading to higher oil demand. But the Fed also "telegraphed its concern regarding U.S. economic growth ... which is intuitively bearish for oil," said energy trader and consultant The Schork Group.
In other Nymex trading, heating oil rose 2.8 cents to $3.04 per gallon and gasoline futures gained 1.7 cents at $2.86 per gallon. Natural gas advanced 2.4 cents to $2.75 per 1,000 cubic feet.
Mutated Kras spins a molecular loop that launches pancreatic cancerPublic release date: 26-Jan-2012 [ | E-mail | Share ]
Contact: Scott Merville smerville@mdanderson.org 713-792-0661 University of Texas M. D. Anderson Cancer Center
UT MD Anderson-led team identifies new potential treatment avenue to block an elusive target
HOUSTON Scientists have connected two signature characteristics of pancreatic cancer, identifying a self-perpetuating "vicious cycle" of molecular activity and a new potential target for drugs to treat one of the most lehal forms of cancer.
The research, reported in the journal Cancer Cell and led by scientists at The University of Texas MD Anderson Cancer Center, connected the molecular dots between:
Mutated versions of Kras, a gene that acts as a molecular on-off switch but gets stuck in the "on" position when mutated.
Heightened activity of a protein complex called NF-?B that controls activation of genes.
"Kras is mutated in 80 to 95 percent of pancreatic ductal adenocarcinomas, and is the most frequent mutation among all cancers," said senior author Paul Chiao, Ph.D., professor in MD Anderson's Department of Molecular and Cellular Oncology.
About 42,000 new cases of pancreatic ductal adenocarcinoma are diagnosed in the United States each year. Estimates vary, but the 5-year survival rate has been 1 to 3 percent for decades and median survival after diagnosis is six months, the researchers note.
Interleukin-1? is a new potential drug target
"There have been many attempts to inhibit mutated Kras, but it's an elusive target that so far has defied treatment," Chiao said. "So if we can't hit Kras, maybe we can target one of its downstream genes. This research identifies some of those genes and suggests that interleukin-1apha (IL-1?) is a potential therapeutic target."
Chiao and colleagues identified IL-1? as a crucial player in a feed-forward loop that:
Begins with mutationally activated Kras triggering a chain reaction that induces IL-1? expression;
This in turn activates NF-?B via the protein kinase IKK2/?, which blocks the inhibitor of NF-?B.
In the cell nucleus, NF-?B oversees gene transcription and regulates a number of inflammation-promoting genes, including IL-1?.
IL-1? and another protein called p62 activate NF-?B which in turn cycles back to perpetuate the loop by activating its activators.
"It's a vicious cycle," Chiao said. The overactive NF-?B fuels pancreatic cancer by activating genes that promote inflammation, the growth of new blood vessels and block programmed cell death.
Chiao has three research grants from the National Cancer Institute to study pancreatic cancer. "We study signaling transduction pathways to try to find out why it's such a bad disease and to find a weak point for targeted therapy," he said.
In the Cancer Cell paper, the authors conclude: "Our findings suggest that the prime mover responsible for cancer-related inflammatory response and the development of pancreatic intraepithelial neoplasia (precancerous lesions) and pancreatic ductal adenocarcinoma is the mutant Kras-initiated constitutive activation of NF-?B."
This process, they further noted, creates a pro-tumor microenvironment by promoting inflammation, creation of new blood vessels and tissue repair that is similar to conditions found in inherited pancreatitis, inflammation of the pancreas that is linked to the development of cancer.
Kras mutation, IL-1?, NF-?B go together with poor survival
The team analyzed mouse and human tumors and mouse strains with mutated Kras expressed in their pancreases. In a series of experiments they found:
Active IKK2/beta the activator of NF-?B was required for the Kras-mutated mice to develop either pancreatic cancer or precancerous legions.
Deletion of IKK2/Beta interrupted Kras-stimulated inflammation and cell proliferation, suggesting that chronic inflammation is a key factor in promoting pancreatic cancer development.
Microarray profiles of gene expression showed that several NF-?B-regulated inflammatory genes were present in high levels in mice with mutated Kras and active IKK2/beta but only found at lower levels in mice with IKK2/beta knocked out.
In human pancreatic tumors, high expression of the same inflammatory genes in the mutated Kras mice were associated with positive lymph node status, high-risk, late tumor stage and poor survival.
Expression of several genes regulated by NF-?B progressed from low levels in normal pancreases to higher levels in precancerous lesions and tumors, including IL-?.
IL-1? was known to be both a target of and an inducer of NF-?B, but its expression had not previously been connected to mutated Kras. The team found that downstream targets of Kras, including IL-1?, are interrupted when IKK2/? is inactivated.
Analysis of 14 human pancreatic cancer tumor samples showed that overexpression of IL-1?, the presence of Kras mutation and the activation of NF-?B are correlated and are associated with poor survival.
Continued activation of NF-?B and its gene transcription activity are sustained by IL-1? and p62.
###
Co-authors with Chiao are Jianhua Ling, Ph.D., Rulying Zhao, M.D., Ph.D., Qianghua Xia, Ph.D., Zhe Chang, Ph.D., and Mien-Chie Hung, Ph.D., of MD Anderson's Department of Molecular and Cellular Oncology; Ya'an Kang, M.D., Ph.D., and Jason Fleming, M.D., of MD Anderson's Department of Surgical Oncology; Huamin Wang, M.D., Ph.D., and Jinsong Liu, M.D., Ph.D., of MD Anderson's Department of Pathology; Dung-Fang Lee, Ph.D., and Ihor Lemischka, Ph.D., of the Black Family Stem Cell Institute of Mount Sinai School of Medicine; Jin Li, Ph.D., of the Center for Applied Genomics of the Children's Hospital of Philadelphia; and Bailu Peng, Ph.D. of the Guangdong Entomological Institute, Guangdong, China.
The team's research was funded by grants from the National Cancer Institute, including MD Anderson's Cancer Center Core Support Grant.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Mutated Kras spins a molecular loop that launches pancreatic cancerPublic release date: 26-Jan-2012 [ | E-mail | Share ]
Contact: Scott Merville smerville@mdanderson.org 713-792-0661 University of Texas M. D. Anderson Cancer Center
UT MD Anderson-led team identifies new potential treatment avenue to block an elusive target
HOUSTON Scientists have connected two signature characteristics of pancreatic cancer, identifying a self-perpetuating "vicious cycle" of molecular activity and a new potential target for drugs to treat one of the most lehal forms of cancer.
The research, reported in the journal Cancer Cell and led by scientists at The University of Texas MD Anderson Cancer Center, connected the molecular dots between:
Mutated versions of Kras, a gene that acts as a molecular on-off switch but gets stuck in the "on" position when mutated.
Heightened activity of a protein complex called NF-?B that controls activation of genes.
"Kras is mutated in 80 to 95 percent of pancreatic ductal adenocarcinomas, and is the most frequent mutation among all cancers," said senior author Paul Chiao, Ph.D., professor in MD Anderson's Department of Molecular and Cellular Oncology.
About 42,000 new cases of pancreatic ductal adenocarcinoma are diagnosed in the United States each year. Estimates vary, but the 5-year survival rate has been 1 to 3 percent for decades and median survival after diagnosis is six months, the researchers note.
Interleukin-1? is a new potential drug target
"There have been many attempts to inhibit mutated Kras, but it's an elusive target that so far has defied treatment," Chiao said. "So if we can't hit Kras, maybe we can target one of its downstream genes. This research identifies some of those genes and suggests that interleukin-1apha (IL-1?) is a potential therapeutic target."
Chiao and colleagues identified IL-1? as a crucial player in a feed-forward loop that:
Begins with mutationally activated Kras triggering a chain reaction that induces IL-1? expression;
This in turn activates NF-?B via the protein kinase IKK2/?, which blocks the inhibitor of NF-?B.
In the cell nucleus, NF-?B oversees gene transcription and regulates a number of inflammation-promoting genes, including IL-1?.
IL-1? and another protein called p62 activate NF-?B which in turn cycles back to perpetuate the loop by activating its activators.
"It's a vicious cycle," Chiao said. The overactive NF-?B fuels pancreatic cancer by activating genes that promote inflammation, the growth of new blood vessels and block programmed cell death.
Chiao has three research grants from the National Cancer Institute to study pancreatic cancer. "We study signaling transduction pathways to try to find out why it's such a bad disease and to find a weak point for targeted therapy," he said.
In the Cancer Cell paper, the authors conclude: "Our findings suggest that the prime mover responsible for cancer-related inflammatory response and the development of pancreatic intraepithelial neoplasia (precancerous lesions) and pancreatic ductal adenocarcinoma is the mutant Kras-initiated constitutive activation of NF-?B."
This process, they further noted, creates a pro-tumor microenvironment by promoting inflammation, creation of new blood vessels and tissue repair that is similar to conditions found in inherited pancreatitis, inflammation of the pancreas that is linked to the development of cancer.
Kras mutation, IL-1?, NF-?B go together with poor survival
The team analyzed mouse and human tumors and mouse strains with mutated Kras expressed in their pancreases. In a series of experiments they found:
Active IKK2/beta the activator of NF-?B was required for the Kras-mutated mice to develop either pancreatic cancer or precancerous legions.
Deletion of IKK2/Beta interrupted Kras-stimulated inflammation and cell proliferation, suggesting that chronic inflammation is a key factor in promoting pancreatic cancer development.
Microarray profiles of gene expression showed that several NF-?B-regulated inflammatory genes were present in high levels in mice with mutated Kras and active IKK2/beta but only found at lower levels in mice with IKK2/beta knocked out.
In human pancreatic tumors, high expression of the same inflammatory genes in the mutated Kras mice were associated with positive lymph node status, high-risk, late tumor stage and poor survival.
Expression of several genes regulated by NF-?B progressed from low levels in normal pancreases to higher levels in precancerous lesions and tumors, including IL-?.
IL-1? was known to be both a target of and an inducer of NF-?B, but its expression had not previously been connected to mutated Kras. The team found that downstream targets of Kras, including IL-1?, are interrupted when IKK2/? is inactivated.
Analysis of 14 human pancreatic cancer tumor samples showed that overexpression of IL-1?, the presence of Kras mutation and the activation of NF-?B are correlated and are associated with poor survival.
Continued activation of NF-?B and its gene transcription activity are sustained by IL-1? and p62.
###
Co-authors with Chiao are Jianhua Ling, Ph.D., Rulying Zhao, M.D., Ph.D., Qianghua Xia, Ph.D., Zhe Chang, Ph.D., and Mien-Chie Hung, Ph.D., of MD Anderson's Department of Molecular and Cellular Oncology; Ya'an Kang, M.D., Ph.D., and Jason Fleming, M.D., of MD Anderson's Department of Surgical Oncology; Huamin Wang, M.D., Ph.D., and Jinsong Liu, M.D., Ph.D., of MD Anderson's Department of Pathology; Dung-Fang Lee, Ph.D., and Ihor Lemischka, Ph.D., of the Black Family Stem Cell Institute of Mount Sinai School of Medicine; Jin Li, Ph.D., of the Center for Applied Genomics of the Children's Hospital of Philadelphia; and Bailu Peng, Ph.D. of the Guangdong Entomological Institute, Guangdong, China.
The team's research was funded by grants from the National Cancer Institute, including MD Anderson's Cancer Center Core Support Grant.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Alysha Ulrich, 10, left foreground, from Oley, Pa., waits in line to go through the Pasquerilla Spiritual Center on the Penn State campus for the viewing for former Penn State coach Joe Paterno Wednesday, Jan. 25, 2012 in State College, Pa. The second day of a three-day period of public mourning for Paterno will culminate with the funeral and burial for the Hall of Fame football coach who became the face of Penn State University. (AP Photo/Alex Brandon)
Alysha Ulrich, 10, left foreground, from Oley, Pa., waits in line to go through the Pasquerilla Spiritual Center on the Penn State campus for the viewing for former Penn State coach Joe Paterno Wednesday, Jan. 25, 2012 in State College, Pa. The second day of a three-day period of public mourning for Paterno will culminate with the funeral and burial for the Hall of Fame football coach who became the face of Penn State University. (AP Photo/Alex Brandon)
Mourners react as they file through the Pasquerilla Spiritual Center on the Penn State campus for the viewing for former Penn State coach Joe Paterno, Tuesday, Jan. 24, 2012, in State College, Pa. Paterno died Sunday morning. (AP Photo/Alex Brandon)
Blaze Feury, right, a member of the Penn State rugby team, gives out hot chocolate to mourners in line to go through the Pasquerilla Spiritual Center on the Penn State campus for the viewing for former Penn State coach Joe Paterno Wednesday, Jan. 25, 2012 in State College, Pa. The second day of a three-day period of public mourning for Paterno will culminate with the funeral and burial for the Hall of Fame football coach who became the face of Penn State University. (AP Photo/Alex Brandon)
A mourner reads a newspaper while in line to go through the Pasquerilla Spiritual Center on the Penn State campus for the viewing for former Penn State coach Joe Paterno Wednesday, Jan. 25, 2012 in State College, Pa. The second day of a three-day period of public mourning for Paterno will culminate with the funeral and burial for the Hall of Fame football coach who became the face of Penn State University. (AP Photo/Alex Brandon)
Mourners line up to go through the Pasquerilla Spiritual Center on the Penn State campus for the viewing for former Penn State coach Joe Paterno Wednesday, Jan. 25, 2012 in State College, Pa. The second day of a three-day period of public mourning for Paterno will culminate with the funeral and burial for the Hall of Fame football coach who became the face of Penn State University. (AP Photo/Alex Brandon)
STATE COLLEGE, Pa. (AP) ? Penn State security had to turn away mourners as viewing hours for the late Joe Paterno ended Wednesday after thousands of students, alumni and admirers had filed past the football coach's closed casket to pay their respects.
The second of three days of events for Paterno was to culminate with a private funeral service and his burial in the afternoon. Penn State will host a public memorial on Thursday at its basketball arena.
The outpouring of support for the Hall of Fame coach was huge, with hundreds of people lined up outside a campus spiritual center throughout the morning in temperatures around freezing. Members of Penn State's rugby team handed out hot chocolate and took donations for the Special Olympics and the student run dance marathon fundraiser ? the two organizations Paterno's family requested receive donations in lieu of flowers.
Paterno served as head coach for 46 years and won two national titles before being fired last November in the wake of child sex-abuse scandal involving a former assistant.
The last few months have been emotionally wrenching for the school's students and alumni, but mourners over the past two days have focused on the inspiration Paterno provided to them, his accomplishments both on and off the field and his philanthropy.
First in line Wednesday was David Brown, who left his home in Greensburg at midnight and drove more than two hours to State College then prepared to wait a few hours outside until the doors opened.
"I wouldn't have been surprised if there were 1,000 people here," he said.
Behind him was John Myers, 70, who drove more than two hours from Tamaqua to arrive at 5 a.m. ? three hours before the viewing was scheduled to begin.
"It's worth it," Myers said. "Joe was one of the best, if not the best, football coaches ever."
The 85-year-old Paterno died Sunday of lung cancer. He had been ousted just days before learning of his diagnosis. Paterno's son, Scott, has said his father was not bitter and remained upbeat until the end of his life.
Jerry Sandusky, the former defensive coordinator at the center of the abuse scandal, has been charged with molesting 10 boys over a period of 15 years. He has pleaded not guilty and is on bail, awaiting trial. Paterno was criticized in the days after Sandusky's arrest for not going to authorities outside campus when he was told of an allegation against the retired assistant in 2002.
Admirers put the case aside.
Tom Haack, a small business owner from Camp Hill, took off work to pay his respects to Paterno. The 59-year-old Haack said he chose Penn State to get his master's degree in business in the late 1980s, partly due to his admiration for the coach.
"His ethics, doing things the right way, excellence in everything you do, all of that attracted me and attracted many others to Penn State," he said. "I think his influence made it a better school and helped make it what it is today."
Thousands waited in line Tuesday on an overcast winter afternoon for the first day of visitation at the Pasquerilla Spiritual Center, where Paterno family members regularly attend services.
Inside the hall, the coach's body lay in a brown hardwood casket topped by a spray of white roses. About six feet away sat a stylized black-and-white picture of the man who became lovingly known on campus as "JoePa," smiling and peering out through his trademark thick-rimmed glasses.
Paterno's casket had an "honor guard" of two Penn State players ? one past and one present. Some mourners stopped for a moment of reflection, or to genuflect in the interfaith hall.
Others fought back tears and sniffles. The only other sounds were the occasional clicks of news photographers taking pictures.
Paterno won 409 ? a record for major college football ? in a career admired by peers as much for its longevity as its success. Paterno also took as much pride in the program's graduation rates, often at or close to the top of the Big Ten.
"The passion, the love that he gave almost gave you a sense that you wanted to give it back to him," Penn State men's basketball coach Patrick Chambers said after escorting his team to the worship hall Tuesday evening. "We're forever indebted to him and we will continue to work as hard as we can."
Four friends got in line at 6:30 a.m. to pay their respects, going up to the casket as a group to say goodbye.
"It's hard to say goodbye to somebody that you feel you've known all along," said John Whitney, a 21-year-old junior from Sparta, N.J. "A lot of us have never met him, but he's had such a big influence on everybody's life around here."
Heather Hoffman, a 19-year-old sophomore from Marlton, N.J., cited Paterno's contributions to academics along with athletics.
"It was time for all of us to pay tribute to him and give thanks because we're all here in part because of him," Hoffman said.
Karen Gilchrist, a Penn State fan from Scranton, brought three of her five children to the viewing. Seven-year-old Tiffany and 8-year-old Johnny both wore rolled-up khaki pants and black sneakers in honor of Paterno.
"There's going to be no one like him in my lifetime or theirs," said Gilchrist, cradling the third child, 6-month-old Valentina. "I wanted them to be part of a historic day. I felt compelled."
Anonymous communications provider AnComm is being acquired by the parent company of SchoolMessenger, a major provider of notification services for K-12 and higher education.
AnComm's service, Talk About It, is a hosted online system that allows students to report incidents of violence, threats, bullying, depression, and other issues to teachers and administrators anonymously. It also provides e-mail capabilities for students and allows members of a school community to participate in polls, with some schools choosing to use the polling system for class elections and the like. According to SchoolMessenger, it's currently in use by about 300,000 students in the United States.
SchoolMessenger, operated by Reliance Communications, is an Internet-based alert and communications system designed specifically for schools. It provides e-mail and voice notification for a variety of devices, SMS text messaging, classroom messaging, posting to major social networking sites, translation to 50 languages, Web- and phone-based parent access, and various reporting tools. It's in use by "thousands" of schools in all 50 states, according to the company.
?As on-campus safety concerns and incidents have escalated over the last decade, thousands of schools and districts nationwide have turned to SchoolMessenger to provide messaging and notification solutions that allow them to connect and communicate directly with millions of parents, students and staff every day,? said Sanford Kenyon, president and CEO of Reliance Communications, in a statement released Tuesday. ?Talk About It is a natural extension of our suite of on-demand solutions that can provide customers with an affordable, one-of-a-kind communications tool that allows students to break the ?code of silence? and seek immediate help from trusted school staff members before tragedy strikes. We believe that just as emergency notification solutions have become a ?must have? in K-12, anonymous communication tools will quickly be adopted to address the myriad of on-campus challenges raised by bullying, stress, family problems, academic pressures and more.?
As part of the acquisition, AnComm CEO Carter B. Myers will join SchoolMessenger as vice president of anonymous communications solutions.
According to information released today by SchoolMessenger, Talk About It is available to all schools, regardless of notification provider. Additional details can be found on the SchoolMessenger Talk About It portal.
BRUSSELS/TEHRAN (Reuters) ? The European Union banned imports of oil from Iran on Monday and imposed a number of other economic sanctions, joining the United States in a new round of measures aimed at deflecting Tehran's nuclear development program.
In Iran, one politician responded by renewing a threat to blockade the Strait of Hormuz, an oil export route vital to the global economy, and another said Tehran should cut off crude shipments to the EU immediately.
That might hurt Greece, Italy and other ailing economies which depend heavily on Iranian oil and, as a result, won as part of the EU agreement a grace period until July 1 before the embargo takes full effect. Angry words on either side helped nudge benchmark Brent oil futures above $110 a barrel on Monday.
A day after a U.S. aircraft carrier, accompanied by a flotilla that included French and British warships, made a symbolically loaded voyage into the Gulf in defiance of Iranian hostility, the widely expected EU sanctions move is likely to set off yet more bellicose rhetoric in an already tense region.
Some analysts say Iran, which denies accusations that it is seeking nuclear weapons, could be in a position to make them next year. So, with Israel warning it could use force to prevent that happening, the row over Tehran's plans is an increasingly pressing challenge for world leaders, not least U.S. President Barack Obama as he campaigns for re-election in November.
Israeli Prime Minister Benjamin Netanyahu, who has voiced skepticism about the chances of Iran being persuaded by non-military tactics, called the EU sanctions a "step in the right direction" but said Iran was still developing atomic weapons.
Israel, assumed to have the only nuclear arsenal in the Middle East, views the Iranian nuclear program as a threat to its survival.
Meeting in Brussels, foreign ministers from the 27-state EU, which as a bloc is Iran's second biggest customer for crude after China, agreed to an immediate ban on all new contracts to import, purchase or transport Iranian crude oil and petroleum products. However, EU countries with existing contracts to buy oil and petroleum products can honor them up to July 1.
EU officials said they also agreed to freeze the assets of Iran's central bank and ban trade in gold and other precious metals with the bank and state bodies.
Along with U.S. sanctions imposed by Obama on December 31, the Western powers hope that choking exports and hence revenue can force Iran's leaders to agree to curbs on a nuclear program the West says is intended to yield weapons.
EU SEEKS TALKS
The United Nations' nuclear watchdog, the International Atomic Energy Agency, confirmed plans for a visit next week by senior inspectors to try and clear up suspicions raised about the purpose of Iran's nuclear activities. Tehran is banned by international treaty from developing nuclear weaponry.
"The Agency team is going to Iran in a constructive spirit, and we trust that Iran will work with us in that same spirit," IAEA chief Yukiya Amano said in a statement announcing the December 29-31 visit. "The overall objective of the IAEA is to resolve all outstanding substantive issues."
EU foreign policy chief Catherine Ashton said of the new sanctions: "I want the pressure of these sanctions to result in negotiations ... I want to see Iran come back to the table and either pick up all the ideas that we left on the table ... last year ... or to come forward with its own ideas."
Iran has said lately that it is willing to hold talks with Western powers, though there have been mixed signals on whether conditions imposed by either side make new negotiations likely.
The Islamic Republic insists it is enriching uranium only for electricity and other civilian uses.
It has powerful defenders against the Western action in the form of Russia and China, which argue that the new sanctions are unnecessary, and can also probably count on China and other Asian countries to go on buying much of its oil, despite U.S. and European efforts to dissuade them.
Russia Foreign Minister Sergei Lavrov, classifying the EU embargo among "aggravating factors," said Moscow believed there was a good chance that talks between the six global powers and Iran could resume soon and that Russia would try to steer both Iran and the West away from further confrontation.
A member of Iran's influential Assembly of Experts, former intelligence minister Ali Fallahian, said Tehran should respond to the delayed-action EU sanctions by stopping sales to the bloc immediately, denying the Europeans time to arrange alternative supplies and damaging their economies with higher oil prices.
"The best way is to stop exporting oil ourselves before the end of this six months and before the implementation of the plan," the semi-official Fars news agency quoted him as saying.
He reiterated that Iran could close the Strait of Hormuz, the narrow channel between the Gulf and open sea through which a third of all oil tanker traffic passes to importers around the world.
Washington has said it will not tolerate any closure, a position underlined by Sunday's passage through the strait of a U.S. flotilla around the carrier Abraham Lincoln, accompanied by two European frigates, Britain's Argyll and France's La Motte-Picquet.
HORMUZ THREAT
While Iran's Revolutionary Guards, possibly aware of the warships' impending arrival, had backed away on Saturday from a threat made by a vice president last month to prevent "even one drop of oil" passing through the strait if the West embargoed Iran's crude, a senior member of parliament said on Monday that the closure remained an option if exports were disrupted.
"If any disruption happens regarding the sale of Iranian oil, the Strait of Hormuz will definitely be closed," Mohammad Kossari, deputy head of parliament's foreign affairs and national security committee, told Fars.
Going further, he referred to previous U.S. warnings that it would use force to break any Iranian blockade of the channel and threatened wider violence against Washington's global interests.
"If America seeks adventures after the closure of the Strait of Hormuz, Iran will make the world unsafe for Americans in the shortest possible time," Kossari said.
"It is in America's interests to accept a powerful Iran and not seek military adventures."
While the Western powers were at pains to describe their naval movement through the strait as routine, a view echoed by the Revolutionary Guards, they also stressed its symbolism.
"On this occasion HMS Argyll and a French vessel joined a U.S. carrier group transiting through the Strait of Hormuz, to underline the unwavering international commitment to maintaining rights of passage under international law," Britain's defense ministry said in a statement.
In Paris, spokesman Thierry Burkhard said: "It's a sign to Iran if they want to consider it like that."
Iran, the world's No. 5 oil exporter and also rich in natural gas, says it is refining uranium and developing other nuclear technologies to meet rising energy needs. But the U.N. nuclear watchdog agency reported in November that it had evidence suggesting Iran had worked on designing an atomic bomb.
The unprecedented effort to take Iran's 2.6 million barrels of oil per day off international markets has kept global prices high, pushed down Iran's rial currency and caused a surge in the cost of basic goods for Iranians. [nL5E8CN0M9]
(Additional reporting by Robin Pomeroy and Mitra Amiri in Tehran, David Brunnstrom in Brussels, Adrian Croft in London, John Irish in Paris, Alexei Anishchuk in Sochi, Ari Rabinovitch and Jeffrey Heller in Jerusalem and Fredrik Dahl in Vienna; Writing by Alastair Macdonald; Editing by Mark Heinrich)
LOS ANGELES (Reuters) - "The Artist" continued its love affair with American cinema after winning best-produced film on Saturday at the Producers Guild Awards (PGA), boosting its chances for an Oscar nod ahead of the Academy Award nominations next week.
The silent black-and-white French comedy, starring Jean Dujardin and Berenice Bejo, is a homage to the pre-talkie era of Hollywood in the 1920s and 1930s and tells the story of a fading silent movie star as sound began entering the world of cinema.
"When Michel Hazanavicius and I dreamed of making "The Artist," we knew we were dreaming of writing a love letter to American cinema. We never knew in return we would get a taste of the American dream," Thomas Langmann, the film's producer, said in his acceptance speech in Beverly Hills.
The film has been sweeping awards ceremonies in the run up to the Oscars, winning best picture at the Critics Choice and Golden Globes earlier this month.
It was up against nine other films in contention for best-produced film on Saturday, including female-led comedy "Bridesmaids," civil rights drama "The Help," and Steven Spielberg's epic tale "War Horse."
"The Adventures of Tintin," produced by Spielberg, picked up best-produced animated film.
The Producers Guild awards are significant in the race to the Academy Awards on February 26, as many of the 5,000-plus members of the PGA, are members of the Academy of Motion Picture Arts and Sciences, who vote for the Oscars.
For the last four years, the producers' best-produced film picks have gone on to win the best picture Oscar, with "No Country For Old Men" in 2008, "Slumdog Millionaire" in 2009, "The Hurt Locker" in 2010 and "The King's Speech" in 2011.
Other PGA award winners on Saturday included "Beats, Rhymes & Life: The Travels of a Tribe Called Quest" for best-produced documentary, which explores the journey of influential hip-hop group A Tribe Called Quest.
Angelina Jolie received the Stanley Kramer award for "In the Land of Blood and Honey," which she wrote, directed and produced, an accolade reserved for contributions that highlight provocative social issues.
The Oscar-winning actress delivered a sober acceptance speech, noting that when war-film "Schindler's List" won a PGA in 1994 during the Bosnian war, "the world turned a blind eye" to the atrocities happening in Eastern Europe at the time.
Spielberg was awarded the coveted David O'Selznick achievement award and comic-book legend Stan Lee received the Vanguard award, presented by "Spiderman" actor Tobey Maguire. Both received standing ovations as they took the stage.
ABC's "Modern Family" was named best-produced television comedy for the second year running, while HBO's "Boardwalk Empire" was named best-produced TV drama. PBS' British period drama "Downtown Abbey" was named best-produced long-form television series.
(Reporting by Piya Sinha-Roy; Editing by Paul Simao)
SUNDAY, Jan. 22 (HealthDay News) -- Researchers have identified three new genomic regions they believe are linked with breast cancer that may help explain why some women develop the disease.
All three newly identified areas "contain interesting genes that open up new avenues for biological and clinical research," said researcher Douglas Easton, a professor of genetic epidemiology at the University of Cambridge in England.
Breast cancer is the most common cancer among women, with about 1 million new cases annually worldwide and more than 400,000 deaths a year.
Scientists conducting genome-wide association studies -- research that looks at the association between genetic factors and disease to pinpoint possible causes -- had already identified 22 breast cancer susceptibility loci. Locus is the physical location of a gene or DNA sequence on a chromosome.
"The three [newly identified] loci take the number of common susceptibility loci from 22 to 25," said Easton.
However, the three new susceptibility loci might explain only about 0.7 percent of the familial risks of breast cancer, bringing the total contribution to about 9 percent, the researchers said.
Michael Melner, scientific program director for the American Cancer Society, said this current research adds some important new clues to existing evidence, but he agreed that the number of cases likely associated with these three variants is probably low.
"So the total impact in terms of patients would be fairly small," Melner said.
The study is published online Jan. 22 in Nature Genetics.
To find the new clues, Easton's team worked with genetic information on about 57,000 breast cancer patients and 58,000 healthy women obtained from two genome-wide association studies.
The investigators zeroed in on 72 different single nucleotide polymorphisms (SNPs). A SNP -- pronounced "snip" -- is a change in which a single base in the DNA differs from the usual base. The human genome has millions of SNPs, some linked with disease, while others are normal variations.
The researchers focused on three SNPs -- on chromosomes 12p11, 12q24 and 21q21.
Easton's team found that the variant on the 12p11 chromosome is linked with both estrogen receptor-positive breast cancer (which needs estrogen to grow) and estrogen receptor-negative breast cancer. The other two variants are only linked with ER-positive cancers, they said.
One of the newly identified variants is in an area with a gene that has a role in the development of mammary glands and bones. Easton said it was already known that mammary gland development in puberty is an important period in terms of determining later cancer risk. "But these are the first susceptibility genes to be shown to be involved in this process," he said.
One of the other SNPs is in an area that can affect estrogen receptor signaling, the researchers found.
Melner, noting some of the research is "fine tuning" of other work, said in his view the new understanding of the signaling pathways and their genetic links is the most important finding.
"When you delineate a pathway, you bring up new potential targets for therapy," he said. "The more targets you have, you open up the potential for having multiple drugs and attacking a cancer more easily, without it becoming more resistant."
Overall, Melner added, the results underscore the complexity of the different mechanisms involved in breast cancer development.
More information
For more about the genetics of breast cancer, visit the American Cancer Society.
Having said all this, Sotomayor then launches into a terrifying exposition about all the ways in which government surveillance no longer actually requires any physical intrusion, and she notes that Scalia?s majority opinion offers no future guidance for regulating such surveillance. Sotomayor cautions that new surveillance systems will fundamentally alter the relationship between government and citizens. She writes, ?I would ask whether people reasonably expect that their movements will be recorded and aggregated in a manner that enables the Government to ascertain, more or less at will, their political and religious beliefs, sexual habits, and so on.? She goes on to warn about an even more worrisome violation of privacy when one?s personal information is voluntarily disclosed to third parties, noting, ?I for one doubt that people would accept without complaint the warrantless disclosure to the government of a list of every Web site they had visited in the last week, or month, or year.? Because she joins on with Scalia?s majority opinion, however, these musings are?at least for now?just high-tech musings.
Owning a small business is tough. Carissa Reiniger has been working in small business development for over seven years and says she's seen countless entrepreneurs and small business owners run into what she calls the "cash flow catch 22": If I had more money, I could make more time -- and vice versa. What's more, the large majority of startups and small businesses that fail, she believes, don't hit the deadpool because their ideas were terrible, but instead because their owners' health declined, or their spouses were fed up with them working 80 hours a week, or they didn't have the stamina or resources to push on. That's why Carissa founded Silver Lining -- to help small business owners make enough money so that they can keep doing what they love. To help jack up the success rates of SMBs, she and her team created "The Slap", or the Silver Lining Action PLan.
BENGHAZI, Libya (Reuters) ? The deputy head of Libya's ruling National Transitional Council (NTC) said on Sunday he was resigning after a series of protests against the new government which the country's leader warned could drag Libya into a "bottomless pit."
The protests have pitched the NTC into its deepest crisis since Muammar Gaddafi was overthrown with help from NATO powers last year, and they raise new questions about the council's ability to govern the oil exporting country.
Late Saturday, a crowd demanding the government's resignation forced their way into the NTC's local headquarters in Benghazi while the NTC chief was inside, in the most serious show of anger at the authorities since Gaddafi's ouster.
The NTC has the support of Western powers, but it is unelected, has been slow to restore basic public services, and some Libyans say too many of its members are tarnished by ties to Gaddafi.
Abdel Hafiz Ghoga, vice-president of the NTC and one of the council's highest-profile members, was the target of some of the protesters' criticism. Last week, students jostled him when he visited a university in Benghazi and he had to be pulled to safety.
"My resignation is for the benefit of the nation and is required at this stage," Ghoga told Al Jazeera television.
He said the national consensus that helped the country rise up and end Gaddafi's 42-year rule had not lasted into peace-time, giving way to what he called an atmosphere of hatred.
"I do not want this atmosphere to continue and negatively affect the National Transitional Council and its performance," said Ghoga, who also acted as the NTC's spokesman.
DISAPPOINTED HOPES
Protesters say the NTC has failed to live up to the aspirations of the revolt against Gaddafi, the most violent of the "Arab Spring" uprisings.
"We hoped for security, peace and transparency. We have seen the opposite," said Miftah Al-Rabia, 28, who was standing outside the NTC's Benghazi headquarters Sunday with a group of protesters.
NTC chief Mustafa Abdel Jalil, speaking at a news conference in Benghazi just over an hour before Ghoga announced he was resigning, appealed to the protesters to be more patient.
"We are going through a political movement that can take the country to a bottomless pit," he said. "There is something behind these protests that is not for the good of the country."
"The people have not given the government enough time and the government does not have enough money. Maybe there are delays, but the government has only been working for two months. Give them a chance, at least two months."
He said he had accepted the resignation of Benghazi's mayor, Saleh El-Ghazal, following the protests, and promised elections to choose the mayor's successor.
In a glimpse of the lack of coordination which Western diplomats say pervades the workings of the NTC, Abdel Jalil was asked if Ghoga would be stepping down and said he would not.
Sources in the NTC, who spoke on condition of anonymity, said Ghoga has not submitted a letter of resignation.
They said he was angry at being manhandled at the university and that a delegation had gone to his home to try to talk him out of resigning.
The location of the protests is particularly galling for the NTC. Benghazi, in eastern Libya, was the birthplace of the revolt against Gaddafi's rule and the site of the NTC's headquarters during the revolt.
HASTILY-FORMED COUNCIL
The protests add to the list of challenges facing the NTC.
It is struggling to bring to heel dozens of armed militias who have carved the country into rival fiefdoms and are so far refusing to join a newly created national army.
Foreign states are worried about the NTC's capacity to secure its borders against arms traffickers, al Qaeda insurgents and migrants trying to reach Europe illegally.
The NTC was formed in the early days of the revolt against Gaddafi from a hastily-assembled group of lawyers, government officials who defected, Muslim clerics, tribal leaders and civil society activists.
At the time, Gaddafi's troops were using automatic weapons to fire on protests in Benghazi and elsewhere, and there was little time to vet the members.
But nearly six months on from the moment the rebellion took control of the capital Tripoli, Libyans are started to question the council's legitimacy.
In particular, some people have cast doubt over the loyalties of former Gaddafi lieutenants who are now in the NTC. These include Abdel Jalil himself, who was justice minister under Gaddafi before defecting early in the uprising.
The council says it will dissolve itself once elections are held for a transitional national assembly. That vote is scheduled to take place in about six months.
At the NTC headquarters in Benghazi Sunday, smashed windows bore witness to the protests Saturday night. Guards in camouflage fatigues patrolled the building.
"We still don't know who exactly is in the NTC. There is no transparency," said Al-Rabia, a protester standing outside the building with a group of about 30 other men.
Another protester, 24-year-old Mohammed Mahmoud, said he fought against Gaddafi during the revolt and wounded his shoulder and hand.
"We fought on the front line and received injuries but we did not see the NTC with us," he said. "I have one single question: Why has the NTC failed at everything except selling oil? We want to correct the path of the revolution."
(Additional reporting by Omar Fahmy in Cairo, Ali Shuaib and Taha Zargoun in Tripoli and Mohammad Al Tommy in Benghazi; Writing by Christian Lowe; Editing by Elizabeth Piper)
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Public release date: 26-Jan-2012
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Owning a small business is tough. Carissa Reiniger has been working in small business development for over seven years and says she's seen countless entrepreneurs and small business owners run into what she calls the "cash flow catch 22": If I had more money, I could make more time -- and vice versa. What's more, the large majority of startups and small businesses that fail, she believes, don't hit the deadpool because their ideas were terrible, but instead because their owners' health declined, or their spouses were fed up with them working 80 hours a week, or they didn't have the stamina or resources to push on. That's why Carissa founded