Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/193394766?client_source=feed&format=rss
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Tuesday, January 31, 2012
T-Mobile Plans to Cap Domestic Data Roaming Starting April 5th [T-Mobile]
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Monday, January 30, 2012
Israeli settler seeks to beat Netanyahu in primary
Israeli politician Moshe Feiglin poses for a portrait in an office Sunday Jan. 29, 2012, in the coastal town of Caesarea. Feiglin, a hardline Jewish settler who supports cash incentives to empty the West Bank and Gaza of Palestinians is running against Israel's prime minister in Tuesday's ruling Likud party's primary, a race he has little chance of winning but one in which he could deliver an embarrassing blow to the country's leader. (AP Photo/Dan Balilty)
Israeli politician Moshe Feiglin poses for a portrait in an office Sunday Jan. 29, 2012, in the coastal town of Caesarea. Feiglin, a hardline Jewish settler who supports cash incentives to empty the West Bank and Gaza of Palestinians is running against Israel's prime minister in Tuesday's ruling Likud party's primary, a race he has little chance of winning but one in which he could deliver an embarrassing blow to the country's leader. (AP Photo/Dan Balilty)
Israeli politician Moshe Feiglin poses for a portrait Sunday Jan. 29, 2012, in an office in the coastal town of Caesarea. Feiglin, a hardline Jewish settler who supports cash incentives to empty the West Bank and Gaza of Palestinians is running against Israel's prime minister in Tuesday's ruling Likud party's primary, a race he has little chance of winning but one in which he could deliver an embarrassing blow to the country's leader. (AP Photo/Dan Balilty)
JERUSALEM (AP) ? A hard-line Jewish settler who wants to pay Palestinians to leave the West Bank and Gaza is running against Israel's prime minister in Tuesday's ruling party primary election.
Moshe Feiglin has little chance of defeating Prime Minister Benjamin Netanyahu, but he could deliver an embarrassing blow to the country's leader in his fourth try for leadership of the Likud, none of which have had a realistic shot at success.
Experts say Feiglin could get a third of the vote in the closed party primary, reflecting the view of hard-liners that Netanyahu, despite his uncompromising worldview, is not hawkish enough.
"I am providing an alternative," said Feiglin, 49. "The world expects ... much more than creating a terrorist country right in the heart of the land of the Bible," referring to a Palestinian state in the West Bank.
Israeli nationalists believe the West Bank must remain under Israeli control for religious and security reasons. Though Netanyahu backed that view for years, his movement has edged toward compromise in recent years, and Netanyahu himself has accepted the concept of creating a Palestinian state.
Feiglin founded a nationalist movement that blocked highway intersections around the country in 1995 to protest partial peace accords between Israel and the Palestinians, and he opposes further peace talks.
Feiglin proposes annexing the West Bank, retaking Gaza ? Israel withdrew in 2005 ? and bolstering a Jewish majority by offering emigration incentive packages of $350,000 to each Arab family in the West Bank and Gaza Strip.
Such extreme positions have the backing of a small but noisy minority of Israelis.
Netanyahu called the snap leadership primary in his Likud Party a year ahead of schedule, raising the possibility of an early general election later this year.
Netanyahu is so popular that no Likud Cabinet ministers or lawmakers dared challenge him, leaving Feiglin as the only other candidate.
Feiglin has steadily gained support over the last three times he has run for Likud party leadership ? from winning 3.5 percent of the vote in his first campaign nine years ago, to scooping up nearly a quarter of the vote in 2007.
Analysts are divided about how the underdog would affect the ruling party.
Avraham Diskin, a Hebrew University political scientist, said the stronger Feiglin performs in the primaries, the more Netanyahu will strive to portray a moderate face to the party by endorsing less hawkish lawmakers around him, he said.
"It doesn't look like (Netanyahu) will give in to the extremists," Diskin said.
Analyst Yaron Ezrahi says if Feiglin wins more than 30 percent of the votes in the primaries, it could push the Likud party's base further right politically and weaken Netanyahu's claim that the ruling party represents the majority of the nation.
"It's very serious. It hurts the Likud's image," Ezrahi said. He called Feiglin's camp an "embarrassing minority" for Netanyahu.
Feiglin's expected gains in Tuesday's primaries come as religious nationalists are preparing for a showdown with the government over plans to evict the unauthorized Migron settlement, which the government says was built on unlawfully seized land from private Palestinian landowners in 2001.
Hard-line lawmakers are threatening to bolt Netanyahu's coalition if Migron is dismantled, and Feiglin's campaign could add more pressure to Netanyahu to find a solution that will satisfy the settlers.
"Netanyahu is fighting a war of survival. But there is no survival without a vision," said Feiglin. "He is losing credit."
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Iran to stop oil exports to "some" countries soon: IRNA (Reuters)
TEHRAN (Reuters) ? Iran's oil minister said on Sunday the Islamic state would soon stop exporting crude to "some" countries, the state news agency IRNA reported.
"Soon we will cut exporting oil to some countries," Rostam Qasemi was quoted by IRNA as saying.
Benchmark Brent crude prices rose to around $111.50 a barrel on Friday on expectations Iran's parliament would vote to halt exports to the European Union as early as next week, in retaliation to EU plans to stop all Iranian crude imports by July amid deepening tension over Tehran's nuclear programme.
Iran's parliament on Sunday postponed the debate over the bill.
(Created by Parisa Hafezi; Editing by Alison Williams)
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Sunday, January 29, 2012
UN nuclear team heads to Iran
VIENNA?? Senior United Nations nuclear inspectors headed to Tehran on Saturday to press Iranian officials to address suspicions that the Islamic state is seeking atomic weapons.
The U.N. International Atomic Energy Agency hopes Iran, which has indicated readiness to discuss the issue for the first time since 2008, will end years of stonewalling on intelligence pointing to an intention to develop nuclear arms technology.
"We are trying ... to resolve all the outstanding issues with Iran, in particular we hope that Iran will engage with us on our concerns regarding the possible military dimensions of Iran's nuclear program," IAEA Deputy Director General Herman Nackaerts told reporters as he prepared to depart from Vienna airport.
But Western diplomats, who have often accused Iran of using such offers of dialogue as a stalling tactic while it presses ahead with its nuclear program, say they doubt Tehran will show the kind of concrete cooperation the IAEA wants.
They say Iran may offer limited concessions and transparency in an attempt to ease intensifying international pressure on the country, a major oil producer, but that this is unlikely to amount to the full cooperation that is required.
The outcome could determine whether Iran will face further international isolation, or whether there are prospects for resuming wider talks between Tehran and the major powers on the nuclear dispute that has sparked fears of war.
The United States and its allies suspect the program has military aims but Tehran says is for peaceful electricity generation.
"The chances of the IAEA's success may depend on how badly Iran wants to avoid harder sanctions," said nuclear expert Mark Hibbs of the Carnegie Endowment for International Peace.
Story: Israel senses bluffing in Iran's retaliation threatsRemarks by Supreme Leader Ayatollah Ali Khamenei's top adviser on international affairs on Saturday suggested Iran was not in the mood for concessions.
"Iran's stance towards its nuclear issue has not changed in term of fundamentals and principles," Ali Akbar Velayati said, according to the ISNA news agency.
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"One important principle is that Iran would not relinquish or withdraw from its peaceful nuclear activities."
The six-member IAEA team of senior officials and experts, headed by Nackaerts, was due to arrive in Tehran early on Sunday.
The three-day visit comes at a time of soaring tension between Iran and the West. The IAEA issued a report in November with details of suspected research and development activities in Iran relevant to nuclear weapons.
The West has seized on the report to ratchet up sanctions aimed at Iran's lifeblood oil exports. Iran hit back on Friday warning it may halt oil exports to Europe next week.
'Appearing to cooperate'
The IAEA team is expected to seek explanations to the issues raised in the report, including information that Iran appears to have worked on a nuclear weapon design, and demand access to sites, officials and documents relevant to the agency's probe.
The IAEA says Iran, which has rejected the allegations as forged and baseless, has not engaged with the agency in a substantive way on these issues since August 2008 and that it keeps receiving intelligence data adding to its concerns.
"There were a huge number of questions raised by the November report. They will be seeking to answer those questions, and it's incumbent on Iran to be supportive," U.S. State Department spokeswoman Victoria Nuland said this week.
IAEA Director General Yukiya Amano has called on Iran to show a "constructive spirit" in the meeting and Iran has said it is willing to discuss "any issues" of interest to the U.N. agency, including the military-linked concerns.
Video: Exclusive: tensions flare near crucial oil chokepointIran's Press TV state television said on its website the IAEA visit was aimed at bolstering cooperation between the two sides "by resolving ambiguities," language Tehran has also used in the past.
The English-language station cited Iran's envoy to the IAEA, Ali Asghar Soltanieh, as saying the main objective was to "thwart plots by enemies who are leveling unfounded allegations" against Iran and to prove its nuclear transparency.
Hibbs said Amano would want to see a "significant step" from Iran, for example by agreeing to more intrusive IAEA inspections or by explaining issues related to the weapons suspicions.
"I'm not very optimistic," Hibbs said. "Iran's track record is of appearing to cooperate whenever they are threatened by penalties."
Meanwhile, European oil companies that are owed oil by Iran could lose out if Iran imposes a ban on crude exports to the EU next week, a measure currently before the Iranian parliament, the head of Iran's state oil company said Saturday.
"Generally, the parties to incur damage from the EU's recent decision will be European companies with pending contracts with Iran," Ahmad Qalebani, head of the National Iranian Oil Co., told the ISNA news agency.
"The European companies will have to abide by the provisions of the buyback contracts," he said. "If they act otherwise, they will be the parties to incur the relevant losses and will subject the repatriation of their capital to problems."
The EU banned imports of oil from Iran 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.
Copyright 2012 Thomson Reuters. Click for restrictions.
Source: http://www.msnbc.msn.com/id/46174915/ns/world_news-mideast_n_africa/
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France, Karzai want faster NATO Afghanistan exit (AP)
PARIS ? President Nicolas Sarkozy says France and Afghan President Hamid Karzai will ask NATO to hand over all combat missions in Afghanistan to Afghan troops in 2013 ? a year earlier than planned.
Sarkozy also says France has informed U.S. President Barack Obama of the proposal and will present it at a meeting of NATO defense ministers early next month.
The move, if confirmed, comes at a time of widespread fatigue among European contributors to the 10-year allied intervention in Afghanistan, and would accelerate a gradual drawdown of NATO troops that Obama planned to see through until the end of 2014.
"We have decided in a common accord with President Karzai to ask NATO to consider a total handling of NATO combat missions to the Afghan army over the course of 2013," Sarkozy said.
News of the French-Afghan proposal comes one week after Sarkozy abruptly suspended France's training missions and joint military patrols with Afghan forces following the shooting death of four unarmed French troops by an Afghan soldier on Jan. 20.
Sarkozy announced that the French will resume their training mission as of Saturday and withdraw its own troops by the end of 2013.
With Karzai at his side, Sarkozy also said authority in the strategic province of Kapisa east of Kabul, where nearly all French troops are deployed, will be handed over to the Afghans in March.
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Friday, January 27, 2012
CNN behind on TV ratings, ahead of rivals online (Reuters)
NEW YORK, Jan 26 (TheWrap.com) ? CNN may lag behind most of its competitors in the television ratings department, but digital is another story.
Citing comScore Media Metrix, CNN said in a blog post that it drew more than 73 million unique visitors across all platforms in 2011, while more than 100 million videos were started on its website.
And what would those numbers mean without a little dig at the competition?
According to CNN, those 73 million unique visitors outpace its main rivals in the TV news space, "beating MSNBC by 38 percent, Fox News by 187 percent, ABC News Digital by 217 percent and CBS Interactive by 260 percent."
If one goes by page views, those percentages balloon even more.
Oddly enough, those numbers might be inversely proportional to television ratings as MSNBC topped CNN in 2011, Fox beat both and the networks outpaced cable.
CNN also claims to be the top destination for mobile news, with 19.5 million unique visitors per month, and the most popular on both Facebook and Twitter.
On mobile and Facebook, Fox News is its closest competitor. On Twitter, it's the New York Times.
(Editing By Zorianna Kit)
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Obama to target rising college tuition costs
ROMULUS, Mich. (AP) - President Barack Obama has put colleges and universities on notice to control tuition costs or face losing federal dollars. Now, schools are waiting to hear how big a stick he plans to wield to enforce his message.
Obama was expected to spell out his plan in a speech Friday at the University of Michigan in Ann Arbor focused on college affordability. His plan could set a new precedent in the federal government's role in controlling the rising costs of college?a move making people in higher education nervous. Obama's speech will cap a three-day post-State of the Union trip by the president to promote different components of his economic agenda in politically important states.
The president hinted at what's ahead in education during his State of the Union address Tuesday night, which coincided with the release of a White House "blueprint" that said he wants to shift federal aid away from colleges that don't keep net tuition down and provide a good value. But it's unclear exactly what pot of federal dollars Obama plans to target and how his plan would work.
The Obama administration already has taken a series of steps to expand the availability of grants and loans and to make loans easier to pay back, and Obama spelled out Tuesday other proposals to make college more affordable such as extending tuition tax breaks and asking Congress to keep loan interest rates from doubling on July. His administration has also targeted career college programs?primarily at for-profit institutions?with high loan default rates among graduates over multiple years by taking away their ability to participate in such programs.
But until now, it has done little to turn its attention to the rising cost of tuition at traditional colleges and universities. The average in-state tuition and fees at four-year public colleges last fall rose 8.3 percent and with room and board now exceed $17,000 a year, according to the College Board. Rising tuition costs have been blamed on a variety of factors, including a decline in state dollars, an over-reliance on federal student loan dollars and competition for the best facilities and professors.
During Tuesday's speech, the president said he'd met with university presidents who described to him ways some universities through technology and redesigning courses were able to help students finish more quickly?efforts that helped curtail costs.
"The point is, it's possible. So let me put colleges and universities on notice: If you can't stop tuition from going up, the funding you get from taxpayers will go down. Higher education can't be a luxury_ it's an economic imperative that every family in America should be able to afford," Obama said.
Barry Toiv, spokesman for the Association of American Universities, said some of its members participated in the meeting Obama referred to and agree that there are good examples of things that can be done to make colleges more efficient. But he said universities are concerned that any proposal by the president "doesn't hurt students" because anything that does is "obviously counterproductive."
Sen. Lamar Alexander, R-Tenn., a former education secretary, said the autonomy of U.S. higher education is what makes it the best of the world, and he questioned whether Obama could enforce any such plan without hurting students. Potentially, billions of dollars are at stake. In the 2010-2011 school year, the federal government awarded $142 billion in federal student aid?most of it directly to students in the form of grants and loans, according to the Education Department.
"It's hard to do without hurting students and it's not appropriate to do," Alexander said. "The federal government has no business doing this."
Some public institutions worry about being unfairly blamed for state cuts that led to an increase in tuition prices. Neal McCluskey, an education analyst at the libertarian Cato Institute, said it's difficult for the federal government to dictate what is a reasonable increase because some colleges and universities might have legitimate reasons to raise tuition some years, such as the need to replace buildings in disrepair.
Obama's plan reflects that in the race between subsidizing tuition with student aid and rising tuition, student aid is going to lose, said Andrew P. Kelly, a research fellow at the American Enterprise Institute. Instead of redesigning their business model or using more online programs to save money, many colleges and universities have made small changes hoping to wait out the nation's fiscal crisis that don't solve the problem long term, Kelly said.
"This signals I think a sense of how acute that problem is and the fact that it can't just be about pouring money into federal student aid programs and hoping that affordability is maintained, that there has to be some kind of way, or at least a signal sent, to the institutions that benefit, and the states, frankly ... that they just can't continue to ratchet up prices and use federal aid to fill in the gaps," Kelly said.
Even though it's not politically popular, McCluskey said a good way to control rising tuition costs would be to cut federal aid to students, which would force colleges and universities to keep tuition low.
This isn't the first time a politician has sought to control tuition costs. In 2003, Rep. Howard "Buck" McKeon, R-Calif., proposed a plan to hold back aid to colleges and universities that raised tuition much faster than inflation. It met resistance from higher education and wasn't passed.
Come Friday, "we'll be watching and listening carefully," said Molly Corbett Broad, president of the American Council on Education.
___
Hefling reported from Washington.
___
Online:
White House: http://www.whitehouse.gov/
Education Department: http://www.ed.gov/
Source: http://www.breitbart.com/article.php?id=D9SH6TEO0&show_article=1
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Thursday, January 26, 2012
Scripps research scientists illuminate cancer cells' survival strategy
![[ Back to EurekAlert! ]](http://www.eurekalert.org/images/back2e.gif){kind=small}
Public release date: 26-Jan-2012[ | E-mail |
Share ] Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
LA JOLLA, CA -- A team led by scientists at The Scripps Research Institute has discovered key elements of a strategy commonly used by tumor cells to survive when they spread to distant organs. The finding could lead to drugs that could inhibit this metastasis in patients with tumors.
A cell that breaks away from the primary tumor and finds itself in the alien environment of the bloodstream or a new organ, normally is destroyed by a process known as apoptosis. But tumor cells that express high levels of a certain surface protein are protected from apoptosis, greatly enhancing their ability to colonize distant organs. How this protein blocks apoptosis and promotes metastasis has been a mysteryuntil now.
"What we found in this study is that it's not the increased expression of the protein per se that protects a tumor cell, but, rather, the cleavage of this protein by proteolytic enzymes," said Scripps Research Professor James P. Quigley. "This cleavage triggers a signaling cascade in the tumor cell that blocks apoptosis." Quigley is the principal investigator for the study, which was recently published online before print by the journal Oncogene.
"We think that a reasonable strategy for inhibiting metastasis would be to try to prevent the cleavage of this surface protein using antibodies or small-molecule drugs that bind to the cleavage site of the protein," said Elena I. Deryugina, a staff scientist in Quigley's laboratory and corresponding author of the manuscript.
A Protein Linked to Poor Outcomes
The cell-surface protein at the center of this research is known as CUB Domain Containing Protein 1 (CDCP1). In 2003, a postdoctoral fellow in Quigley's laboratory, John D. Hooper, discovered and co-named CDCP1 as a "Subtractive Immunization Metastasis Antigen," also finding that it is highly expressed on the surfaces of metastasis-prone human tumor cells.
Quigley's laboratory and others soon found additional evidence that CDCP1 plays a major role in enabling metastasis. Clinical studies reported CDCP1 on multiple tumor types and linked its presence to worse outcomes for patients. Deryugina and Quigley reported in 2009 that CDCP1, when expressed in tumor-like cells, strongly promotes their ability to colonize new tissues and that unique monoclonal antibodies to CDCP1, generated in Quigley's lab, significantly block CDCP1-induced tumor colonization. Hooper, who now leads a laboratory at the Mater Medical Research Institute in Brisbane, Australia, reported in a cell culture study in 2010 that most of the CDCP1 protein on the cell membrane could be cleaved by serine proteases. This cleavage event seems to lead to the biochemical activation of the internal fragment of CDCP1 by a process called tyrosine phosphorylation, in this case involving the cancer-linked protein Src.
"What was missing was evidence in live animals that connected CDCP1 biochemically to the blocking of apoptosis and successful metastasis," said Deryugina.
In the new study, Deryugina and her colleagues in the Quigley laboratory, including first author Berta Casar, a postdoctoral fellow, set out to find such evidence.
In Pursuit of Evidence
Hooper supplied the Scripps Research scientists with transformed human embryonic kidney (HEK) cells, which don't naturally express CDCP1, but were forced to express the gene for CDCP1. Casar and Deryugina injected these CDCP1-expressing HEK cells into chick embryos, and found that the CDCP1 proteins on these HEK cells began to be cleaved by resident enzymes to the shorter form. After 96 hours, the proteins were no longer detectable in their full-size, pre-cleaved form. The CDCP1-expressing HEK cells were four times as likely to survive in the chick embryos than were control CDCP1-negative HEK cells. The same results were obtained with HEK cells that express a mutant, non-cleavable form of the CDCP1 protein.
The Scripps Research team then did experiments in live animals with human prostate cancer cells naturally expressing CDCP1 to show that the cleavage of CDCP1 by a serine protease enzyme is the key event that promotes tumor cell survival. "When we blocked CDCP1 cleavage using our unique anti-CDCP1 antibodies, or added a compound that selectively inhibits serine protease enzymes, CDCP1 was not cleaved, and the CDCP1-expressing cancer cells lost almost all their ability to colonize the tissues of chick embryos," said Casar.
Casar and Deryugina also confirmed that in live animals CDCP1's cleavage leads to the biochemical activation of its internal fragment by tyrosine phosphorylation involving the cancer-linked proteins Src and PKC?. This was followed by the downstream activation of the anti-apoptosis protein Akt and the inhibition of apoptosis-mediating enzymes. The team verified these results with a variety of experimental setups, including tests of tumor-cell lung colonization in mice and tests in which Src signaling was blocked with the anti-Src drug Dasatinib.
Another key experiment by Scripps Research scientists indicated that plasmin, a blood-clot-thinning serine protease, is the principal cleaver of CDCP1 in metastasizing tumor cells. In mice that lack plasmin's precursor molecule, plasminogen, CDCP1-bearing tumor cells showed an absence of CDCP1 cleavage and lost nearly all their ability to survive in lung tissue.
Toward a Promising Strategy
Breakaway tumor cells commonly travel to distant organs via the bloodstream, so their use of an abundant bloodstream enzyme such as plasmin as a survival booster makes sense. "Plasmin has long been linked to cancer," Quigley said. "Unfortunately, it has such an important function in thinning blood clots that using plasmin-inhibiting drugs in cancer patients might do more harm than good."
"Blocking the cleavage of CDCP1 using antibodies or other CDCP1-binding molecules seems to be a more promising strategy," said Deryugina. She and Casar are investigating.
###
The other co-authors of the paper, "Blocking of CDCP1 cleavage in vivo prevents Akt-dependent survival and inhibits metastatic colonization via PARP1-mediated apoptosis of cancer cells," were Yaowu He and Mary Iconomou, of the Hooper laboratory. For more information, see http://www.nature.com/onc/journal/vaop/ncurrent/abs/onc2011555a.html
The study was supported by the National Institutes for Health, the Science and Innovation Ministry of Spain, and the National Health and Medical Research Council of Australia.
[ | 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.
Public release date: 26-Jan-2012[ | E-mail |
Share ] Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
LA JOLLA, CA -- A team led by scientists at The Scripps Research Institute has discovered key elements of a strategy commonly used by tumor cells to survive when they spread to distant organs. The finding could lead to drugs that could inhibit this metastasis in patients with tumors.
A cell that breaks away from the primary tumor and finds itself in the alien environment of the bloodstream or a new organ, normally is destroyed by a process known as apoptosis. But tumor cells that express high levels of a certain surface protein are protected from apoptosis, greatly enhancing their ability to colonize distant organs. How this protein blocks apoptosis and promotes metastasis has been a mysteryuntil now.
"What we found in this study is that it's not the increased expression of the protein per se that protects a tumor cell, but, rather, the cleavage of this protein by proteolytic enzymes," said Scripps Research Professor James P. Quigley. "This cleavage triggers a signaling cascade in the tumor cell that blocks apoptosis." Quigley is the principal investigator for the study, which was recently published online before print by the journal Oncogene.
"We think that a reasonable strategy for inhibiting metastasis would be to try to prevent the cleavage of this surface protein using antibodies or small-molecule drugs that bind to the cleavage site of the protein," said Elena I. Deryugina, a staff scientist in Quigley's laboratory and corresponding author of the manuscript.
A Protein Linked to Poor Outcomes
The cell-surface protein at the center of this research is known as CUB Domain Containing Protein 1 (CDCP1). In 2003, a postdoctoral fellow in Quigley's laboratory, John D. Hooper, discovered and co-named CDCP1 as a "Subtractive Immunization Metastasis Antigen," also finding that it is highly expressed on the surfaces of metastasis-prone human tumor cells.
Quigley's laboratory and others soon found additional evidence that CDCP1 plays a major role in enabling metastasis. Clinical studies reported CDCP1 on multiple tumor types and linked its presence to worse outcomes for patients. Deryugina and Quigley reported in 2009 that CDCP1, when expressed in tumor-like cells, strongly promotes their ability to colonize new tissues and that unique monoclonal antibodies to CDCP1, generated in Quigley's lab, significantly block CDCP1-induced tumor colonization. Hooper, who now leads a laboratory at the Mater Medical Research Institute in Brisbane, Australia, reported in a cell culture study in 2010 that most of the CDCP1 protein on the cell membrane could be cleaved by serine proteases. This cleavage event seems to lead to the biochemical activation of the internal fragment of CDCP1 by a process called tyrosine phosphorylation, in this case involving the cancer-linked protein Src.
"What was missing was evidence in live animals that connected CDCP1 biochemically to the blocking of apoptosis and successful metastasis," said Deryugina.
In the new study, Deryugina and her colleagues in the Quigley laboratory, including first author Berta Casar, a postdoctoral fellow, set out to find such evidence.
In Pursuit of Evidence
Hooper supplied the Scripps Research scientists with transformed human embryonic kidney (HEK) cells, which don't naturally express CDCP1, but were forced to express the gene for CDCP1. Casar and Deryugina injected these CDCP1-expressing HEK cells into chick embryos, and found that the CDCP1 proteins on these HEK cells began to be cleaved by resident enzymes to the shorter form. After 96 hours, the proteins were no longer detectable in their full-size, pre-cleaved form. The CDCP1-expressing HEK cells were four times as likely to survive in the chick embryos than were control CDCP1-negative HEK cells. The same results were obtained with HEK cells that express a mutant, non-cleavable form of the CDCP1 protein.
The Scripps Research team then did experiments in live animals with human prostate cancer cells naturally expressing CDCP1 to show that the cleavage of CDCP1 by a serine protease enzyme is the key event that promotes tumor cell survival. "When we blocked CDCP1 cleavage using our unique anti-CDCP1 antibodies, or added a compound that selectively inhibits serine protease enzymes, CDCP1 was not cleaved, and the CDCP1-expressing cancer cells lost almost all their ability to colonize the tissues of chick embryos," said Casar.
Casar and Deryugina also confirmed that in live animals CDCP1's cleavage leads to the biochemical activation of its internal fragment by tyrosine phosphorylation involving the cancer-linked proteins Src and PKC?. This was followed by the downstream activation of the anti-apoptosis protein Akt and the inhibition of apoptosis-mediating enzymes. The team verified these results with a variety of experimental setups, including tests of tumor-cell lung colonization in mice and tests in which Src signaling was blocked with the anti-Src drug Dasatinib.
Another key experiment by Scripps Research scientists indicated that plasmin, a blood-clot-thinning serine protease, is the principal cleaver of CDCP1 in metastasizing tumor cells. In mice that lack plasmin's precursor molecule, plasminogen, CDCP1-bearing tumor cells showed an absence of CDCP1 cleavage and lost nearly all their ability to survive in lung tissue.
Toward a Promising Strategy
Breakaway tumor cells commonly travel to distant organs via the bloodstream, so their use of an abundant bloodstream enzyme such as plasmin as a survival booster makes sense. "Plasmin has long been linked to cancer," Quigley said. "Unfortunately, it has such an important function in thinning blood clots that using plasmin-inhibiting drugs in cancer patients might do more harm than good."
"Blocking the cleavage of CDCP1 using antibodies or other CDCP1-binding molecules seems to be a more promising strategy," said Deryugina. She and Casar are investigating.
###
The other co-authors of the paper, "Blocking of CDCP1 cleavage in vivo prevents Akt-dependent survival and inhibits metastatic colonization via PARP1-mediated apoptosis of cancer cells," were Yaowu He and Mary Iconomou, of the Hooper laboratory. For more information, see http://www.nature.com/onc/journal/vaop/ncurrent/abs/onc2011555a.html
The study was supported by the National Institutes for Health, the Science and Innovation Ministry of Spain, and the National Health and Medical Research Council of Australia.
[ | 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.
Source: http://www.eurekalert.org/pub_releases/2012-01/sri-srs012612.php
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Sweden's Ericsson says Q4 profits dropped (AP)
STOCKHOLM ? LM Ericsson, the world-leading wireless equipment maker in terms of market share, on Wednesday shocked the market by posting a much worse-than-expected fourth-quarterly result, mainly blaming operators for turning cautious due to the global financial turmoil.
Shares in the company took a severe beating in the opening minutes of the Stockholm stock exchange, tumbling 13 percent to 8.95 kronor ($1.33).
The company, headquartered in Stockholm in Sweden, said profits in the final quarter of 2011 fell by more than two-thirds compared with a year earlier, reaching only 1.15 billion kronor ($170 million) from a previous 4.32 billion kronor. Aside from the woes on the financial markets, it also said operator investment spending had slowed down due to a period of high investment in capacity as well as caution linked to political unrest in some countries.
Although sales were more or less flat in the October-December period, rising by 1 percent to 63.67 billion kronor, the tighter budgets for operators led to a severe squeeze of its gross margin, which fell to 30.2 percent from a previous 34.7 percent.
Losses in its Sony Ericsson joint venture also hurt the results, it said. Ericsson last year sold its share in Sony Ericsson to Sony, but the deal is being finalized in this quarter.
For the full year 2011, however, a 12 percent rise in sales led to a net profit of 12.19 billion kronor, also up 12 percent from the full year in 2010, the company said.
Greger Johansson, an analyst with research firm Redeye said the results fell way below expectations, describing them as "very weak," especially pointing to the disappointing sales figures in Ericsson's core unit, Networks.
"It's pretty much weaker on all areas," he said.
Ericsson CEO Hans Vestberg said that although his company expects operators "to continue to be cautious with spending, reflecting factors such as macro economic and political uncertainty" in the short term, "the industry fundamentals for longer-term positive development remain solid."
"With our global scale and presence, as well as technology and services leadership, we are well positioned to continue to drive and lead the industry development," he said.
Ericsson is the world leader in rolling out and upgrading mobile network infrastructure. Its biggest competitors are China's Huawei and Finnish-German joint venture Nokia Siemens.
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Wednesday, January 25, 2012
Apple iPhone now more popular than all Android smartphones in US combined: report (Digital Trends)
In the US, Apple?s iPhone has surpassed the smartphone market share of all Android devices combined, according to new numbers out from research firm Kantar Worldpanel ComTech, as reported by Reuters. But the difference is almost invisible: Apple now owns 44.9 percent of the market; handsets running Google?s Android operating system now own just 44.8 percent.
Though the difference in popularity may be small, Apple?s growth is anything but. By Kantar?s count, Apple?s market share has doubled over the past year alone, while Android devices have fallen about 5 percent, from a high of 50 percent. Windows Phone devices now account for less than 2 percent, on average, across nine key world markets.
A recent study from Nielsen corroborates Kantar?s numbers. According to Nielsen, 44.5 percent of customers who purchased a smartphone during the last three months of 2012 bought an iPhone, and 57 percent of those buyers got the iPhone 4S, Apple?s newest handset. At that time, Android still remained the No. 1 smartphone category, with 46.9 percent of buyers going for a Google-powered device. ?
News of Apple?s new-found dominance in the US smartphone game follows the company?s latest quarterly earnings report, which showed record iPhone and iPad sales, and a record revenue of $46.3 billion. Apple sold 37.04 million iPhones during the quarter (which spanned the final three months of 2011), a 128 percent increase over the same period in 2010. And iPad sales jumped 111 percent year-over-year, to 15.43 million.
While Apple?s iPhone sales are staggering, it?s more surprising that the entire Android market put together is failing to beat back a single line of handsets ? even if they are Apple handsets. We would be surprised in Android doesn?t surge back into first place over the coming months, as more and more customers go for far faster 4G LTE-enabled devices, which the iPhone 4S is not.
This article was originally posted on Digital Trends
More from Digital Trends
Android is on almost half the world?s smartphones
ComScore: Android dominates market, Verizon iPhone 4 boosts Apple
Rumor: Apple working on smaller, more affordable iPhones
Worldwide smartphone sales rose 96 pct in summer 2010
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Rwanda war-crimes suspect deported (AP)
MONTREAL ? A Rwandan man has been deported from Canada for allegedly helping incite Rwanda's 1994 genocide.
Leon Mugesera was taken to an airport in Montreal by Canadian border-services agents and Rwanda's Foreign Minister Louise Mushikiwabo later confirmed in a twitter account note on Monday that he had left on a plane bound for Kigali, Rwanda's capital. Canadian officials did not comment.
Mugesera, 59, had been living in Canada for nearly two decades and was wanted in Rwanda on charges stemming from the 1994 massacre.
A former Rwandan political operative, Mugesera delivered a fiery anti-Tutsi speech in the leadup to the 1994 genocide. In that 1992 speech, he referred to Tutsis as "cockroaches" and called for their extermination.
He is among the first Western refugee claimants to be sent back to face charges.
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Tuesday, January 24, 2012
Obama: US must reclaim values of fairness for all
On the day of his State of the Union address, President Barack Obama walks from the Oval Office along the Colonnade of the White House in Washington, Tuesday, Jan. 24, 2012. (AP Photo/Haraz N. Ghanbari)
On the day of his State of the Union address, President Barack Obama walks from the Oval Office along the Colonnade of the White House in Washington, Tuesday, Jan. 24, 2012. (AP Photo/Haraz N. Ghanbari)
Graphic shows number of words used in official and unofficial State of the Union addresses; will be updated following Obama???s 2012 speech
On the day of his State of the Union address, President Barack Obama walks from the Oval Office along the Colonnade of the White House in Washington, Tuesday, Jan. 24, 2012. (AP Photo/Haraz N. Ghanbari)
Following the Republicans' weekly strategy session, Senate Minority Leader Mitch McConnell of Ky. talks to reporters on Capitol Hill in Washington, Tuesday, Jan. 24, 2012. McConnell took aim at President Obama who will be delivering his State of the Union address later. (AP Photo/J. Scott Applewhite)
Following the Democrats' weekly strategy session, Senate Majority Leader Harry Reid of Nev., talks to reporters on Capitol Hill in Washington, Tuesday, Jan. 24, 2012. (AP Photo/J. Scott Applewhite)
WASHINGTON (AP) ? Keeping the American dream alive has become "the defining issue of our time," President Barack Obama says. He's using Tuesday night's State of the Union address to draw a stark election-year line with Republicans over how to keep the United States from eroding further into a nation of haves and have-nots.
In excerpts of his speech released in advance, Obama attacked income equality and offered his own economic revival plan built upon boosting manufacturing, energy and education. He warned Republicans in Congress that he will fight them if they try to obstruct him or restore an economy gutted by "outsourcing, bad debt and phony financial profits."
Driving everything about the speech: Jobs, including Obama's own. He was essentially making his case for re-election as he spelled out where he wants to take the country.
Obama was making his pitch to a bitterly divided Congress and to a country underwhelmed by his handling of the economy. Targeting anxiety about a slumping middle class, Obama was calling for the rich to pay more in taxes. Every proposal was to be underlined by the idea that hard work and responsibility still count.
"No debate is more important," Obama said in the excerpts released by the White House ahead of the 9 p.m. EST speech.
"We can either settle for a country where a shrinking number of people do really well while a growing number barely get by. Or we can restore an economy where everyone gets a fair shot, everyone does their fair share and everyone plays by the same set of rules," the president said.
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Late NBC executive's letters donated to USC (Reuters)
LOS ANGELES (TheWrap.com) ? The family of Brandon Tartikoff -- the youngest programming chief in NBC history -- has donated the late television and film executive's collection of correspondence and effects to the University of Southern California, the school said Monday.
George Lucas, a USC alumnus and benefactor, had urged Tartikoff's widow, Lilly Tartikoff, to make the donation. Lilly Tartikoff will officially present the documents to Lucas in a USC School of Cinematic Arts ceremony in the fall.
"We are very grateful to Lilly Tartikoff for this unique and generous gift," Lucas said in a statement. "It is a staggering collection for students of television and popular culture, providing rare insight into the mind and achievements of arguably one of the most prominent and influential creative executives in television history."
The collection includes more than 4,000 pieces of correspondence that Tartikoff sent and received between 1979 and 1992.
According to USC, the letters pertain "to programming and project evaluations during his storied reign at NBC, as well as personal correspondences, such as letters of congratulations to then new morning show host David Letterman."
The letters have been unavailable to the public since Tartikoff died in 1997 from Hodgkin's Disease.
"Brandon would be delighted to know that his papers were being made available to SCA students," Lilly Tartikoff said in a statement. "He was in many ways a teacher himself, and loved sharing his experiences in this business with others coming up the ranks."
Tartikoff brought NBC from the No. 3 to the No. 1 network and is credited for the original concepts and blueprints of "The Cosby Show," "Miami Vice," "The Golden Girls," "The A-Team" and "Hill Street Blues."
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Monday, January 23, 2012
No formal bid yet for bankrupt Saab: receivers (Reuters)
STOCKHOLM (Reuters) ? The receivers for bankrupt car maker Saab are talking with several bidders and would like to sell the Swedish company as a whole, but there have been no formal bids yet, they said on Saturday.
Saab was declared bankrupt in December after frantic rescue efforts by its former owner, Swedish Automobile.
Chinese group Zhejiang Youngman Lotus Automobile could make a fresh bid in the coming week, sources have told Reuters.
"We have had discussions with a number of interested parties. Some of them are interested in the factory as a whole and some of them are interested in parts of it," Hans Bergvist, one of the receivers, told Reuters in a telephone interview.
"There have been no formal bids," added fellow receiver Anne-Marie Pouteaux.
General Motors, (GM.N) which still licenses technology to Saab, blocked earlier rescue efforts, saying it did not want help competitors.
Swedish newspaper Dagens Industri has reported Turkish private equity firm Brightwell, as well as Indian utility vehicle maker Mahindra and Mahindra Ltd (MAHM.NS) are also interested.
Neither Bergvist nor Pouteaux would name any of the parties interested in buying Saab or parts of it.
"We do have an objective to sell a totality (of Saab)," added Pouteaux.
Saab hit crisis point early last year after its 2010 sales fell short of target.
Its production line came to a standstill in April and it has not made a car since then.
Swedish Automobile tried several times to line up buyers or financing, but all efforts so far have failed.
(Reporting by Patrick Lannin; Editing by Alison Birrane)
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Golden Nuggets: All Business For The 49ers - Niners Nation
Last week, I had something not entirely unlike a a battle speech in the Golden Nuggets, prior to the game against the New Orleans Saints. There won't be anything like that today ... no theatrics, nothing. We're a team of destiny, and none of you need to get pumped up for this game. More than that, our San Francisco 49ers beat the New York Giants once before - this is business as usual, nothing more. I'm just going to get to your gameday links, and then get to sleep, with hopes of waking up just before kickoff. Here's the links, and as always, GO NINERS!
A quick look at the weather report for Sunday's NFC Championship Game (Examiner.com)
New York Defense Not As Intimidating As Some Say (SB Nation Bay Area)
49ers v. Giants, matchup to watch (SacBee.com)
The nation wants a Giants/Pats Super Bowl ... or do they? (BayAreaSportsGuy,com)
Giants finally arrive in S.F. after flight delay (CSNBayArea.com)
Easy to see why Smith is succeeding (ESPN.com)
Character-laden coach builds new 49ers identity (SFGate.com)
49ers fans are most overrated in the NFL (N.Y. Daily News) (PressDemocrat.com)
Ex-Giants WR Tyree sees red (and gold) at Empire State Building (NFL.com)
49ers-Giants: Matchups to watch (CSNBayArea.com)
Giants vs. 49ers: matchups (Yahoo.com)
Niners, Giants about to add to rich postseason rivalry (PressDemocrat.com)
Andrew Iupati making his mark (Scout.com)
Spencer's kindness strikes chord with lifelong 49ers fan (CSNBayArea.com)
Underdog fight (49ers.com)
Being a Sheep
Be sure to follow @NinersNation on Twitter as well as on Facebook. You can follow SB Nation Bay Area on Twitter @sbnbayarea and also on Facebook. My personal Twitter is @ninnyjams.
If you're new here, you can register for a free account to participate in the discussion and create your own fanposts here at Niners Nation and across our entire network of 300+ sports blogs.
Source: http://www.ninersnation.com/2012/1/22/2724675/49ers-links-nfc-championship-preview-giants-news
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Sunday, January 22, 2012
Why People Love Beats By Dre Headphones [Music]
Source: http://feeds.gawker.com/~r/gizmodo/full/~3/0j0E2uydZRo/why-people-love-beats-by-dre-headphones
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A Bit of My RP
This is a bit of introduction to the RP I was going to post... I lost it all when my picture ended up being too big. -Growl-
Someone's Journal
June 19th, 2453
Its odd. The past few days I have been hearing weird, echoing sounds whenever I am outside. Everyone else has been commenting on them as well. Police don't know what they are, and the military base near here has been sending jets into the sky almost non-stop. The sonic booms from their engines are shaking my house each time they pass overhead. I hate it. But, the sounds are oddly soothing. I wonder what they are?
June 21st, 2453
Its scary. The noises have become non-stop, and they are more eerie now. Deep, whistling sounds echo into the house through the closed windows and shake the glasses in the cupboards. Several plates have already been broken. Mom says that if they continue, we're going to move our stuff into the storm shelter.
July 4th, 2453
Mom's idea of moving into the storm shelter was a good idea. Not a day after we got most of our things settled, a storm hit and ruined our house. We're living off of canned food. The emergency organizations are offering shelter to those who don't have any and are providing food to those in need. Mom has already gathered several trunk loads. She seems to think this won't stop. My Daddy thinks otherwise. He's been sitting back, relaxing and reading his books. He is so cool and calm! He helps us, but I can hear Mom muttering under her breath sometimes about him not doing enough.
July 30th, 2453
She killed him. (-Tear Stains are present across the page. This is the only thing written across two pages.-)
August 7th, 2453
Mom killed Dad when he had his back turned... Buried the axe we were using to cut up trees into his back and then cut off his head. She doesn't know I saw. I am afraid. She has been slowly changing these past few days. Her eyes seem more yellow and her nails are definitely longer than ever before. She snaps at me at the smallest things and the meat we have managed to save isn't fully cooked anymore. My steak was almost all raw. I had to recook it myself over the fire. I burnt it, but it was better than what my mom gave me... I am worried.
August 20th, 2453
Mom came home bloody. She was smiling though, dragging in what appeared to be a large black bag that was bleeding. I asked her what was in it but all she told me was that we wouldn't have to worry about anymore meat for awhile. She said that the old man down the street went out and shot a few deer. I don't believe her, but I need to eat. We ran out of food about four days ago and I have been slowly getting hungrier and hungrier. Mom however seems to have food. I need to find it so I can eat as well as she is.
August 25th, 2453
I... Found out what was in the bag. (-Handwriting is shaky and uneven.)
Apparently, when Mom said the old man went out and shot some deer, she was lying. The Old Man was the one that was shot. He is missing an arm and a leg... I think mom has been feeding me his body. I have started to refuse to eat any meat and I think she's getting suspicious of me. She's been guarded in her actions and has been carrying that... axe. I've taken to carrying around my Daddy's knife. I've kept it sharp like he taught me to. I even practiced a bit with it! If Mom decides to hurt me... I will fight back.
September 14th, 2453
She did it... (The Handwriting is shakier than last time and blood drops and smears cover the page.)
She attacked me. It was after I confronted her.... (-A particularly large splatter of blood here.-)
She got me good... The axe is burried deep between my ribs. It hurts to move... Even to breath and everything feels all tingly... I can't see very well. I think am dying... And if I am, whoever finds this.. Please, remember me...
My name was Julia Anne Elderwood. I was in middle school. I was 11. (-The second 1 is scratched across the page until it ends.-)
Source: http://feedproxy.google.com/~r/RolePlayGateway/~3/jFVMLyIGki4/viewtopic.php
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Saturday, January 21, 2012
Capsule reviews of `Haywire,' other new releases (AP)
"Haywire"_ A straight-up action picture may sound unusual coming from Steven Soderbergh, but as he's repeatedly demonstrated throughout his career, he's keen to experiment with every genre imaginable. And if you look closely here, you'll find it reveals glimmers of some of his greatest hits, including "The Limey," "Traffic" and the "Ocean's" movies. By comparison, it feels like minor Soderbergh: zippy, hugely entertaining and well-crafted as always (since he once again serves as his own cinematographer and editor), but not one of his more important films. It does, however, mark the auspicious film debut of MMA superstar Gina Carano as special-ops bad-ass Mallory Kane. Carano had never acted before, and not only did she do all her own stunts, she had to do them in a way that she wouldn't injure her male co-stars, including Ewan McGregor, Michael Fassbender and Channing Tatum. Her dialogue delivery may seem a bit stiff ? and she has acknowledged that Soderbergh made some tweaks to her voice in post-production ? but she has tremendous presence: an intriguing mix of muscular power and eye-catching femininity. Mallory must figure out who double-crossed her, and why, after a mission in Barcelona. Soderbergh wisely emphasizes Carano's strengths. He lets the elaborate fight scenes play out ? lets us see every kick, punch and body slam ? without a lot of needless edits and even without any music. You may feel as if you've been worked over as well. But in a good way. R for some violence. 93 minutes. Three stars out of four.
? Christy Lemire, AP Movie Critic
___
"Miss Bala"_ Gerardo Naranjo may have made the least-glamorous movie ever about a pageant queen. And that's what makes it so beautiful. With long, fluid takes that create a mesmerizing tension, the Mexican director and writer initially draws us into a world of youthful optimism, one which ends up being wildly unpredictable and increasingly desperate. Sadly, it couldn't be more relevant in depicting the brutal violence plaguing Mexico's northern border areas. At its center is the gorgeous, leggy Stephanie Sigman, a former model making her striking film debut. Sigman stars as Laura Guerrero, a young woman who hopes to be crowned the next Miss Baja California. (The title is a play on words: "bala" means bullet in Spanish.) When Laura goes to a club with her best friend, she finds herself in the wrong place at the wrong time, as gang members shoot the place up while targeting some DEA agents who are partying there. Laura escapes briefly but she's seen too much, and ends up becoming their captive pawn. The group's leader is the wily Lino (a subtly menacing Noe Fernandez), who's been terrorizing northern Mexico with his minions while working the angles across the United States border, as well. Lino at first forces Laura to run a few errands, but the tasks become more and more dangerous. R for language, some brutal violence and sexuality. In Spanish with English subtitles. 113 minutes. Three stars out of four.
? Christy Lemire, AP Movie Critic
___
"Red Tails" ? The famed Tuskegee Airmen get the John Wayne-style heroic rendering they very much deserve, but also a hackneyed and weirdly context-less story that does them a disservice. George Lucas' pet project has the laudable goal of proving all-black movies can be a success, but "Red Tails" reduces a historical story of deep cultural significance to merely a flyboy flick. The film, directed by TV veteran Anthony Hemingway, superimposes the tale of the black World War II pilots on a dated, white genre of 1940s patriotic propaganda. "Red Tails" is blatantly old-fashioned, just with a change in color. It focuses entirely on aerial combat in Europe, skipping all that pesky backstory of black men braving the segregation of Jim Crowe America and, against the odds, rising up at the Tuskegee Institute. Cuba Gooding Jr. and Terrence Howard play higher-ups, but the film is centered on a band of pilots, particularly the brash, talented Joe "Lightning" Little (David Oyelowo) and his alcoholic captain Marty "Easy" Julian (Nate Parker). The script, by John Ridley and Boondocks cartoonist Aaron McGruder is swaggering but hopelessly corny and curiously avoids really fleshing out the Tuskegee Airmen's other battle front: racism at home. The dogfights, though, are elegant and clearly staged, set against a majestic European landscape. PG-13 for some sequences of war violence. 125 minutes. Two stars out of four.
? Jake Coyle, AP Entertainment Writer.
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Friday, January 20, 2012
Federer, Nadal into 4th round at Australian Open (AP)
MELBOURNE, Australia ? Roger Federer made the most of his rare opportunities Friday against the fastest serve in tennis, cashing in with some classic returns in a 7-6 (6), 7-5, 6-3 win over Ivo Karlovic to reach the fourth round of the Australian Open.
The four-time Australian Open champion fended off Karlovic's set point in the tiebreaker with a return that brought the 6-foot-10 Croatian to the net, then lobbed just over him.
"I knew going in it was going to be tough. I played him 10 times, and we've played some breakers. I knew it could come down to a few here and there," said Federer, who broke Karlovic once in each of the second and third sets. He only faced two breakpoints himself, including the pivotal one in the opening tiebreaker. "I definitely got a bit fortunate and started to play better as the match went on."
For his part, Karlovic thought it was "one in a 100 I'm gonna lose that point."
"It was unlucky," Karlovic said. "I didn't really expect him to do that. I was there, I just miscalculated how much I was jumping. If I would have won that, everything would be different but that's life."
Federer is now 10-1 against Karlovic and looking increasingly confident at Melbourne Park, where he has collected four of his 16 Grand Slam titles.
He and Rafael Nadal are on the same side of the draw at a major for the first time since 2005 and could meet in the semifinals.
Second-ranked Nadal had a 6-2, 6-4, 6-2 win earlier Friday over Slovakia's Lukas Lacko to advance without dropping a set or show any signs that a freak knee injury is bothering him.
Nadal, who won the 2009 Australian title but has gone out in the quarterfinals due to injuries in the last two years, felt a crack and then sharp pain in his right knee while sitting in a chair at his hotel on the weekend and was concerned that he might not be able to play in his opening match. Medical tests didn't show any serious damage, and he has had the knee heavily taped in his three matches since.
"The knee is fine. That's important thing," the 10-time major winner said. "The match was a really complete match, a really solid one.
"Very happy about my game. Being in fourth round without losing a set, it's fantastic news."
Nadal will next meet fellow Spaniard Feliciano Lopez, who beat No. 16 John Isner 6-3, 6-7 (3), 6-4, 6-7 (0), 6-1 to put the last U.S. man out of the draw.
No. 7 Tomas Berdych beat No. 30 Kevin Anderson of South Africa 7-6 (5), 7-6 (1), 6-1 and will next play No. 10 Nicolas Almagro of Spain, who beat 21st-seeded Stanislas Wawrinka of Switzerland 7-6 (2), 6-2, 6-4.
Germany's Philipp Kohlschreiber defeated Alejandro Falla of Colombia 6-3, 6-2, 7-6 (3) in another third-round match.
On the women's side, top-seeded Caroline Wozniacki continued her quest for a first major title with a 6-2, 6-2 win over Monica Niculescu of Romania and third-seeded Victoria Azarenka beat Mona Barthel 6-2, 6-4 in a match between champions of two warmup tournaments.
No. 8 Agnieszka Radwanska beat Kazakhstan's Galina Voskoboeva 6-2, 6-2 and will next meet No. 22 Julia Gorges, who beat Italian Romina Oprandi 3-6, 6-3, 6-1.
Wozniacki, who needs to reach the quarterfinals to have any chance of retaining the No. 1 ranking, wasted one match point and was broken when she was serving for the match. But she broke back immediately to ensure she moved into a Round of 16 encounter against former No. 1 Jelena Jankovic, who beat American Christina McHale 6-2, 6-0.
Wozniacki, who needs to reach the quarterfinals to have any chance of retaining the No. 1 ranking, wasted one match point and was broken when she was serving for the match, but broke back immediately to ensure she moved into the Round of 16.
Azarenka, who beat French Open champion Li Na to win the Sydney International last week, has only lost eight games at Melbourne Park and remains one of three women who can overhaul Wozniacki for the top ranking at the Australian Open.
The 22-year-old from Belarus will next meet Czech player Iveta Benesova, who beat Russian qualifier Nina Bratchikova 6-1, 6-3.
Barthel was on a 10-match winning run in Australia after capturing her first title at the Hobart International last week as a qualifier.
Barthel hit 20 winners ? one more than Azarenka ? but she was broken three times and failed to convert three break opportunities.
Azarenka was annoyed with herself for needing five match points to finish off Barthel, and for running out of challenges before she really needed to review a line call in the last game.
"I've been playing in the end not brave enough to finish the match ... I had to get a little," angry, Azarenka said.
Federer will play the winner of the match between Australian teenager Bernard Tomic, a Wimbledon quarterfinalist last year, and No. 13 Alex Dolgopolov. Both have a vastly different style to Karlovic, who broke Andy Roddick's record for the fastest serve ever in tennis by hitting one at 156 mph in a Davis Cup match last year.
"It's just because he's so tall and makes it unusual to return against," Federer said of the serve. "I've been around the block, faced some good ones."
Yet it unraveled twice when Karlovic needed it, in the tiebreaker and in the 12th game of the second set.
Karlovic was a point from forcing a second-set tiebreaker but Federer stepped it up, earning two set points with some trademark backhands and converting on the second when the tall Croatian netted a volley.
Roddick is already out of the tournament, retiring during his second-round match against Australian veteran Lleyton Hewitt late Thursday.
He needed a medical timeout after injuring his right hamstring in the second set and played 16 more games before finally retiring when Hewitt gained a 3-6, 6-3, 6-4 lead.
"It's a miserable, terrible thing being out there compromised like that," said Roddick, who is hoping to return within three weeks.
Hewitt, who turns 31 next month, goes to the third round against Milos Raonic, the big-serving, 21-year-old Canadian. If Hewitt eliminates an opponent who has dropped only two service games this year, he could face defending champion Novak Djokovic in the fourth round. Djokovic, who won three of the four major titles last year, kept getting better in his 6-3, 6-2, 6-1 win over Santiago Giraldo.
Fourth-seeded Andy Murray, who lost to Djokovic in last year's Australian final, ousted Edouard Roger-Vasselin of France 6-1, 6-4, 6-4. No. 5 David Ferrer beat American Ryan Sweeting 6-7 (4), 6-2, 3-6, 6-2, 6-3, and No. 6 Jo-Wilfried Tsonga downed Ricardo Mello of Brazil 7-5, 6-4, 6-4.
Five-time Australian Open champion winner Serena Williams notched her 500th career singles victory Thursday when she beat Barbora Zahlavova Strycova 6-0, 6-4 in the second round.
"Five hundred is a lot of matches to play, let alone to win," she said, adding that the left ankle she badly sprained two weeks ago wasn't an issue. "It's totally fine. It was my good ankle, so I'm good."
Williams won the Australian Open in 2009 and 2010, but didn't defend her title in 2011 because she was injured.
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