Netflix Fixes a Disruption to Its Video Streaming





A disruption at one of Amazon’s Web service centers hit users of Netflix’s streaming video service on Christmas Eve and was not fully resolved until Christmas Day, a Netflix spokesman said on Tuesday.


The disruption affected Netflix subscribers across the United States, Canada and Latin America and blacked out various devices — including video game consoles and DVD players — that enable users to stream movies and television shows, the Netflix spokesman, Joris Evers, said.


Mr. Evers said the issue was the result of a failure at an Amazon Web Services cloud computing center in Virginia and started at about 3:30 p.m. Eastern time on Monday and was fully restored Tuesday morning, although streaming was available for most users late on Monday.


“We are investigating exactly what happened and how it could have been prevented,” Mr. Evers said.


“We are happy that people opening gifts of Netflix or Netflix-capable devices can watch TV shows and movies and apologize for any inconvenience caused last night,” he added.


A disruption at Amazon Web Services knocked out sites like Flipboard and Foursquare in October, and a storm in June similarly affected services like Netflix, Instagram and Pinterest.


Read More..

Russian Parliament Sends Adoption Ban to Putin





MOSCOW — The upper chamber of Parliament on Wednesday unanimously approved a bill to ban adoptions of Russian children by United States citizens, sending the measure to President Vladimir V. Putin, who has voiced support but not yet said if he will sign it.




Enactment of the adoption ban, which was developed in retaliation for an American law punishing Russians accused of violating human rights, would be the most severe blow yet to relations between Russia and the United States in a year marked by a series of setbacks.


Since Mr. Putin returned to the presidency in May, Russian officials have used a juggernaut of legislation and executive decisions to curtail United States influence and involvement in Russia, undoing major partnerships that began after the fall of the Soviet Union.


In September, the Kremlin ordered the United States Agency for International Development to cease operations here, shutting a wide portfolio of public health, civil society and other initiatives. And officials announced plans to terminate a joint effort to dismantle nuclear, chemical and other nonconventional weapons known as the Nunn-Lugar agreement.


Russia also passed a law requiring nonprofit groups that get financing from abroad to register as “foreign agents,” sharply curtailing the ability of the United States to work with good-government groups, and another law broadening the definition of treason to include “providing financial, technical, advisory or other assistance to a foreign state or international organization.”


The adoption ban, however, is the first step that takes direct aim at the American public and would effectively undo a bilateral agreement on international adoptions that took effect on Nov. 1. The agreement called for heightened oversight in response to several high-profile cases of abuse and deaths of adopted Russian children in the United States.


About 1,000 Russian children were adopted by parents from the United States in 2011, more than any other country, and more than 45,000 such children have been adopted by American parents since 1999.


Pavel Astakhov, Russia’s child rights commissioner, told news agencies on Wednesday that the ban, if enacted, could prevent the departure of 46 children who are ready to be adopted by parents from the United States. Some of those adoptions have already received court approval, he said. And some lawmakers said they believed that the bilateral agreement on adoptions with the United States would be void as of Jan. 1, even though Mr. Putin, at his annual news conference last week, said that changes to the agreement required one-year notice by either side.


The proposed ban has opened a rare split at the highest levels of the Russian government, with several senior officials speaking out against it. And it has provoked a huge public outcry and debate, with critics of the ban saying that it would most hurt Russian orphans, many of whom are already suffering in the country’s deeply troubled foster care and orphanage system.


In debate on Wednesday, lawmakers said that they felt an imperative to retaliate for a law signed by President Obama this month that will punish Russian citizens accused of violating human rights, by prohibiting them from traveling to the United States and from owning real estate or other assets there.


Lawmakers also said that Russia, which has more than 650,000 children living without parental supervision, should take care of them on its own. The vote in the Federation Council was 143 to 0.


“We need to set a plan for the future,” said Valery V. Ryazanksy, a senator from the Kursk region. Then, reiterating a slogan adopted by many lawmakers in recent days, he declared: “Russia without orphans!” Gennady I. Makin, a senator from Veronezh, gave it a slight twist: “Russia without orphanages.”


Several child-welfare advocates have mocked this sort of talk, noting that more than 80,000 children were identified as in need of supervision in 2011 and that the country had been unable to find homes for a vast majority of children eligible for adoption.


There were slightly more than 10,000 adoptions in Russia in 2011, about 3,400 of which were by foreigners.


In addition to banning adoptions by Americans, the bill approved on Wednesday would impose sanctions on American judges and others accused of violating the rights of adopted Russian children in the United States.


A number of cases involving the abuse or even the deaths of adopted Russian children in recent years have generated publicity and outrage in Russia, including a case in which a 7-year-old boy was sent on a flight back to Russia alone by his adoptive mother in Tennessee.


The Russian law was named for Dmitri Yakovlev, a toddler who died of heatstroke in Virginia in 2008, after his adoptive father left him in a parked car for nine hours. The father, Miles Harrison, was acquitted of manslaughter by a judge who ruled that the death was an accident.


Read More..

Israel to Review Curbs on Women’s Prayer at Western Wall





JERUSALEM – Amid outrage across the Jewish diaspora over a flurry of recent arrests of women seeking to pray at the Western Wall with ritual garments – in defiance of Israeli law — Prime Minister Benjamin Netanyahu has asked Natan Sharansky, the chairman of the Jewish Agency, to study the issue and suggest ways to make the site more accommodating to all Jews.




The move comes after more than two decades of civil disobedience by a group called Women of the Wall against regulations, legislation and a 2003 Supreme Court ruling that allow for gender division at the wall, one of Judaism’s holiest sites, and prohibit women from carrying a Torah or wearing prayer shawls there.


Though the movement has struggled to gain traction here in Israel, where the ultra-Orthodox retain great sway over public life, the issue has deepened a divide between the Jewish state and the Jewish diaspora at a time when Israel is battling international isolation over its settlement policy. Critics, particularly leaders of the Reform and Conservative movements in the United States, complain that the government’s recent aggressive enforcement of restrictions at the wall has turned a national monument into an ultra-Orthodox synagogue.


“The prime minister thinks the Western Wall has to be a site that expresses the unity of the Jewish people, both inside Israel and outside the state of Israel,” Ron Dermer, Mr. Netanyahu’s senior adviser, said in an interview Tuesday. “He wants to preserve the unity of world Jewry. This is an important component of Israel’s strength.”


Mr. Sharansky, whose quasi-governmental nonprofit organization handles immigration for the state and is a bridge between Israel and Jews around the world, said that Mr. Netanyahu had asked him on Monday to take up the matter, and that he expected to have recommendations within “a few months.” He and Mr. Dermer said the agenda would include improvements for Robinson’s Arch, a discreet area of the wall designated for coed prayer under the court ruling, and easing of restrictions in the larger area known as the Western Wall plaza, along with the more sensitive questions regarding prayer at the main site.


The Jewish Agency itself stopped having ceremonies for new immigrants in the plaza about two years ago after the Western Wall Heritage Foundation, which controls the site, said that men and women could not sit together. Under pressure from the international groups that provide its financing, the agency on Oct. 30 passed a resolution calling for a “satisfactory approach to the issue of prayer at the Western Wall.”


Asked whether he could imagine a day when women could wear prayer shawls and read Torah at the wall itself, Mr. Sharansky said, “I imagine very easily a situation where everybody will have their opportunity to express their solidarity with Judaism and the Jewish people and the state of Israel in a way he or she wants, without undermining the other.”


“That’s as much as I want to say at this moment,” he added. “Now I have to share this vision with the appropriate bodies.”


Anat Hoffman, chairwoman of Women of the Wall, reacted with cautious optimism to Mr. Netanyahu’s initiative, but said it would not stop the Israel Religious Action Center, of which she is executive director, from filing a Supreme Court petition as soon as next week challenging the ultra-Orthodox majority on the heritage foundation’s board.


“It’s a good thing that after 24 years the highest echelons in Israel are actually paying attention to this rift that is breaking diaspora Jews from Israel,” she said. “The table that should run the Western Wall should have everyone who has an interest in the wall sitting around it.”


Ms. Hoffman said the women’s group would be satisfied if it was allowed to pray at the wall once a month with full regalia, but that the religious action center would like hours each day, between scheduled prayer times, where the gender partition is removed and people can freely enjoy the site as a cultural monument.


“If in the end what happens is that the Robinson’s Arch area will be run by the Jewish Agency instead of the antiquities department, then we’re talking about who’s going to take care of the air conditioning in the back of the bus,” she said. “I don’t care about that. I don’t want to sit in the back of the bus. I want to dismantle the Western Wall Heritage Foundation.”


Abraham H. Foxman, director of the Anti-Defamation League, said he had discussed the wall and other questions of religious pluralism with Mr. Netanyahu in Jerusalem on Monday.


“This is a wise initiative, but it’s only a beginning,” Mr. Foxman said.


Read More..

Gadgetwise Blog: A Gaming Laptop That's Quick and Costly

The word “extreme” may be overused in describing male-dominated activities like the X Games or the cinnamon challenge, but it fits the bill when it comes to the Razer Blade gaming laptop.

It is extremely fast, extremely thin and extremely expensive.

I don’t play computer games so I turned the Razer Blade over to two lifelong gamers, Evan and Morgan Dilks. Evan, as the owner of the Firehouse Coffee Company in Baltimore, has spent plenty of caffeinated play time on game consoles, like the PlayStation 3 and Xbox 360 he currently owns.

The pair tried out Battlefield 3, which came preinstalled for demonstration on the machine. “One of the pros was how fast it was,” said Evan. “The processor is just crazy.” That crazy processor is an Intel Core i7, a quad-core chip found in some high end Macs.

That speed is paired with a 17.3-inch high-definition screen impressive enough that the brothers spent some time watching videos on it. Although the laptop is almost 11-by-17-inches to accommodate the screen, it is less than an inch thick and weighs 6.6 pounds, relatively light for a laptop this size. Part of the way Razer kept it thin was by omitting an optical drive.

What really sets it apart from other laptops is the Switchblade user interface. That is an LCD trackpad that shows game information, like who in your player group is inflicting the most damage on foes. Evan said his brother Morgan adjusted more easily to the controls than he did, but he caught on eventually.

There are also 10 buttons above the trackpad that change their assigned functions depending on the game. They can represent different weapons, and automate actions that would normally take several steps, like drawing and loading a firearm. Or you can create your own custom actions, even for non-gaming software, like if you wanted to use the laptop for Photoshop.

What the brothers did not like about the Razer Blade was the price: $2,500. “That is a huge investment,” said Evan. “Add in accessories like a sound system, headset, game and gaming subscription, and special controllers you might need, and the price keeps rising.”

Read More..

Madrid Journal: Spain Turns Christmas Into a Season of Thrift





MADRID — This is the season when barren stone plazas and broad sidewalks here fill with Christmas markets peddling sweets, candles, holiday decorations and crafts. But alongside the festive stalls this year, another kind of market has sprung up in response to Spain’s hard times.




They are the “mercadillos,” or little markets, where the entrepreneurial-minded have found a niche by gathering and selling the unsold stock of more established retailers whose sales have plummeted, or unwanted clothing and other items from people in need of cash.


Buyers and sellers rely heavily on Facebook and other social networking sites to promote the improvised exchanges, which have transformed the way Spaniards shop for the holidays.


For the hard-pressed, the markets are a bargain hunters’ paradise, and for the jobless, they offer an economic lifeline and a chance to recast their fortunes.


Cristina Aresti and Sofía Bourne had never thought about working in fashion until they lost their jobs, joining the more than 25 percent of Spaniards who are unemployed. But this month they opened Abo Cool Market, a pop-up shop that sold secondhand women’s clothing over six days inside a Madrid furniture store.


The two women said they had intended to limit their sales to 500 items. But given the avalanche of offers from people wanting to sell off their wardrobes, they ended up selecting 800 pieces of clothing, with a combined retail value of more than $59,000.


“We just couldn’t believe how many people now want to sell clothing that they had hardly worn,” Ms. Bourne said. Among the most expensive items on sale — a totem of more prosperous times — was an unworn Gucci silk dress that still bore its original sales tag. It was on sale for $650, about a quarter of the original price.


Ms. Aresti and Ms. Bourne will keep 35 percent of their sales receipts; the rest will go to the women who supplied the clothing. The original owners then have the choice of either retrieving unsold items or donating them to charity groups.


Many of the people running this year’s mercadillos had little or no experience in retail sales. Ms. Bourne was laid off by a real estate company; Ms. Aresti lost her job as director of a company that organizes business conferences.


“I don’t yet know whether my future really lies in fashion,” Ms. Aresti said, “but there comes a point in such a hopeless job market when you’ve at least got to try to reinvent yourself.”


Even merchants with long experience in retail or fashion are borrowing some of the practices of the little markets as a way to lure customers.


“Store sales have been plummeting, so you need to go out of your way to make it fun and worthwhile for people to still do some shopping this Christmas,” said Cristina Terrón, a fashion stylist whose mercadillo sold some clothing she had initially selected for television and movie productions. “Something that started out of economic necessity is now also turning into a fashion.”


On average, Spanish households are set to spend $790 to $920 on Christmas shopping this year, down as much as 38 percent from 2007, before the onset of the economic crisis, according to a study published this month by Esade, a Spanish business school.


Jaime Castelló, a marketing professor and one of the authors of the study, said the crisis was not only reducing spending, but also speeding up changes in consumer habits.


About 70 percent of Spanish households said they would search online before buying any Christmas gifts, and 25 percent said they would not even step into a department store, according to the study. The mercadillos, Mr. Castelló suggested, were “another alternative in this crisis to the traditional buying channels.”


Ana María Menoyo Delgado, 26, said she had “lots of fun” searching the Christmas mercadillo Web sites as she worked her way through her holiday shopping list. At Abo Cool’s market, with her mother’s help, she ended up with two designer hand bags, a skirt and a coat, spending a total of $659.


While bargain hunting is part of the attraction, several buyers said they simply preferred the mercadillos to department stores.


“I can’t stand anymore walking into a conventional luxury store where you are likely to be welcomed by a pretty and young but utterly grumpy sales attendant,” Irene Trigueros, a commodities trader, said as she tried on a pair of secondhand sunglasses.


Some of the mercadillos have even been held in bars. “Having a cocktail while trying on some nice clothing seems to me a perfect way to end the day,” said Alberto Martínez, owner of the 1862 Dry Bar, who allowed his basement to become a mercadillo for three days this month.


Mr. Martínez did not charge any rent, but some of the larger mercadillos add to their revenue by renting out booths in their spaces to smaller sellers, normally for $200 to $400 a weekend.


In Alcobendas, on the outskirts of Madrid, a warehouse was transformed into La Galería del 32, a market that sold, among other things, wine, ham, sculpture, jewelry and handbags. The warehouse used to store electronics equipment and other goods until about three years ago, when the demand for storage space dried up as retail sales slumped.


“This kind of event is a great way for those who exhibit to attract more shoppers, while we earn something from renting the space rather than allowing it to stand empty,” said Leticia Martínez Rubio, one of the organizers.


A charity foundation, the Fundacíon Dar, also took part in the weekend event, encouraging shoppers to bring toys that the foundation would distribute to underprivileged children in the Madrid area.


“Beside having a successful weekend sale, I think it’s also important to keep some of the Christmas spirit,” Ms. Martínez Rubio said.


Read More..

Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct


C.J. Gunther for The New York Times


Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.







For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.




Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.


No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.


And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”


At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.


Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.


“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.


The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.


The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”


Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.


Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.


The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?


In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.


But Nutlins did not work as drugs because they were not absorbed into the body.


Roche, Merck and Sanofi persevered, testing thousands of molecules.


At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.


The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.


Read More..

Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct


C.J. Gunther for The New York Times


Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.







For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.




Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.


No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.


And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”


At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.


Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.


“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.


The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.


The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”


Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.


Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.


The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?


In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.


But Nutlins did not work as drugs because they were not absorbed into the body.


Roche, Merck and Sanofi persevered, testing thousands of molecules.


At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.


The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.


Read More..

Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct


C.J. Gunther for The New York Times


Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.







For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.




Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.


No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.


And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”


At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.


Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.


“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.


The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.


The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”


Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.


Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.


The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?


In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.


But Nutlins did not work as drugs because they were not absorbed into the body.


Roche, Merck and Sanofi persevered, testing thousands of molecules.


At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.


The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.


Read More..

Amazon Book Reviews Deleted in a Purge Aimed at Manipulation





Giving raves to family members is no longer acceptable. Neither is writers’ reviewing other writers. But showering five stars on a book you admittedly have not read is fine.




After several well-publicized cases involving writers buying or manipulating their reviews, Amazon is cracking down. Writers say thousands of reviews have been deleted from the shopping site in recent months.


Amazon has not said how many reviews it has killed, nor has it offered any public explanation. So its sweeping but hazy purge has generated an uproar about what it means to review in an era when everyone is an author and everyone is a reviewer.


Is a review merely a gesture of enthusiasm or should it be held to a higher standard? Should writers be allowed to pass judgment on peers the way they have always done offline or are they competitors whose reviews should be banned? Does a groundswell of raves for a new book mean anything if the author is soliciting the comments?


In a debate percolating on blogs and on Amazon itself, quite a few writers take a permissive view on these issues.


The mystery novelist J. A. Konrath, for example, does not see anything wrong with an author indulging in chicanery. “Customer buys book because of fake review = zero harm,” he wrote on his blog.


Some readers differ. An ad hoc group of purists has formed on Amazon to track its most prominent reviewer, Harriet Klausner, who has over 25,000 reviews. They do not see how she can read so much so fast or why her reviews are overwhelmingly — and, they say, misleadingly — exaltations.


“Everyone in this group will tell you that we’ve all been duped into buying books based on her reviews,” said Margie Brown, a retired city clerk from Arizona.


Once a populist gimmick, the reviews are vital to making sure a new product is not lost in the digital wilderness. Amazon has refined the reviewing process over the years, giving customers the opportunity to rate reviews and comment on them. It is layer after layer of possible criticism.


“A not-insubstantial chunk of their infrastructure is based on their reviews — and all of that depends on having reviews customers can trust,” said Edward W. Robertson, a science fiction novelist who has watched the debate closely.


Nowhere are reviews more crucial than with books, an industry in which Amazon captures nearly a third of every dollar spent. It values reviews more than other online booksellers like Apple or Barnes & Noble, featuring them prominently and using them to help decide which books to acquire for its own imprints by its relatively new publishing arm.


So writers have naturally been vying to get more, and better, notices. Several mystery writers, including R. J. Ellory, Stephen Leather and John Locke, have recently confessed to various forms of manipulation under the general category of “sock puppets,” or online identities used to deceive. That resulted in a widely circulated petition by a loose coalition of writers under the banner, “No Sock Puppets Here Please,” asking people to “vote for book reviews you can trust.”


In explaining its purge of reviews, Amazon has told some writers that “we do not allow reviews on behalf of a person or company with a financial interest in the product or a directly competing product. This includes authors.” But writers say that rule is not applied consistently.


In some cases, the ax fell on those with a direct relationship with the author.


“My sister’s and best friend’s reviews were removed from my books,” the author M. E. Franco said in a blog comment. “They happen to be two of my biggest fans.” Another writer, Valerie X. Armstrong, said her son’s five-star review of her book, “The Survival of the Fattest,” was removed. He immediately tried to put it back “and it wouldn’t take,” she wrote.


In other cases, though, the relationship was more tenuous. Michelle Gagnon lost three reviews on her young adult novel “Don’t Turn Around.” She said she did not know two of the reviewers, while the third was a longtime fan of her work. “How does Amazon know we know each other?” she said. “That’s where I started to get creeped out.”


Mr. Robertson suggested that Amazon applied a broad brush. “I believe they caught a lot of shady reviews, but a lot of innocent ones were erased, too,” he said. He figures the deleted reviews number in the thousands, or perhaps even 10,000.


The explosion of reviews for “The 4-Hour Chef” by Timothy Ferriss shows how the system has evolved from something spontaneous to a means of marketing and promotion. On Nov. 20, publication day, dozens of highly favorable reviews immediately sprouted. Other reviewers quickly criticized Mr. Ferriss, accusing him of buying supporters.


He laughed off those suggestions. “Not only would I never do that — it’s unethical — I simply don’t have to,” he wrote in an e-mail, saying he had sent several hundred review copies to fans and potential fans. “Does that stack the deck? Perhaps, but why send the book to someone who would hate it? That doesn’t help anyone: not the reader, nor the writer.”


As a demonstration of social media’s grip on reviewing, Mr. Ferriss used Twitter and Facebook to ask for a review. “Rallying my readers,” he called it. Within an hour, 61 had complied.


A few of his early reviews were written by people who admitted they had not read the book but were giving it five stars anyway because, well, they knew it would be terrific. “I am looking forward to reading this,” wrote a user posting under the name mhpics.


A spokesman for Amazon, which published “The 4-Hour Chef,” offered this sole comment for this article: “We do not require people to have experienced the product in order to review.”


The dispute over reviews is playing out in the discontent over Mrs. Klausner, an Amazon Hall of Fame reviewer for the last 11 years and undoubtedly one of the most prolific reviewers in literary history.


Mrs. Klausner published review No. 28,366, for “A Red Sun Also Rises” by Mark Hodder. Almost immediately, it had nine critical comments. The first accused it of being “riddled with errors in grammar, spelling and punctuation.” The rest were no more kind. The Harriet Klausner Appreciation Society had struck again.


Mrs. Klausner, a 60-year-old retired librarian who lives in Atlanta, has published an average of seven reviews a day for more than a decade. “To watch her in action is unbelievable,” said her husband, Stanley. “You see the pages turning.”


Mrs. Klausner, who says ailments keep her home and insomnia keeps her up, scoffs at her critics. “You ever read a Harlequin romance?” she said. “You can finish it in one hour. I’ve always been a speed reader.” She has a message for her naysayers: “Get a life. Read a book.”


More than 99.9 percent of Mrs. Klausner’s reviews are four or five stars. “If I can make it past the first 50 pages, that means I like it, and so I review it,” she said. But even Stanley said, “She’s soft, I won’t deny that.”


The campaign against Mrs. Klausner has pushed down her reviewer ratings, which in theory makes her less influential. But when everything is subject to review, the battle is never-ending.


Ragan Buckley, an aspiring novelist active in the campaign against Mrs. Klausner under the name “Sneaky Burrito,” is a little weary. “There are so many fake reviews that I’m often better off just walking into a physical store and picking an item off the shelf at random,” she said.


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At Western Wall, a Divide Over Prayer Deepens


Rina Castelnuovo for The New York Times


Members of Women of the Wall prayed this month while wearing tallits, fringed prayer shawls, and tefillin, leather prayer boxes, both of which Jewish men are told to wear.







JERUSALEM — The face-off at the security gate outside the Western Wall one Friday this month was familiar: for more than two decades, women have been making a monthly pilgrimage to pray at one of Judaism’s holiest sites in a manner traditionally preserved for men, and the police have stopped them in the name of maintaining public order.






Rina Castelnuovo for The New York Times

Bonna Devora Haberman, 52, of Women of the Wall, was confronted by the police this month after trying to bring in her prayer shawl.






But after a flurry of arrests this fall that set off an international outcry, the women arrived for December’s service to find a new protocol ordered by the ultra-Orthodox rabbi who controls the site. To prevent the women from defying a Supreme Court ruling that bars them from wearing ritual garments at the wall, they were blocked by police officers from bringing them in.


“How can you say this to me?” demanded a tearful Bonna Devora Haberman, 52, a Canadian immigrant who helped found the group Women of the Wall in 1988. “I’m a Jew. This is my state.”


The officer was unmoved. “At the Western Wall, you can’t pray with a tallit,” he said, referring to the fringed prayer shawl in Ms. Haberman’s backpack. “You can’t go in with it.”


After years of legislative and legal fights, the movement for equal access for people to pray as they wish at the site has become a rallying cause for liberal Jews in the United States and around the world, though it has long struggled to gain traction here in Israel, where the ultra-Orthodox retain great sway over public life.


This has deepened a divide between the Jewish state and the Jewish diaspora, in which some leaders have become increasingly vocal in criticizing Israel’s policies on settlements in the Palestinian territories; laws and proposals that are seen as antidemocratic or discriminatory against Arab citizens; the treatment of women; and the ultra-Orthodox control over conversion and marriage.


“When my kids start expressing frustration with Israel as a society because what they hear and see from a distance is not welcoming to them in their religious practice — that’s not good for the Jewish people, let alone for the state of Israel,” said Rabbi Steven C. Wernick, the director of the United Synagogue of Conservative Judaism.


Rabbi Levi Weiman-Kelman, an American immigrant who runs Kol Haneshama, a leading Reform synagogue here, said Women of the Wall “is an issue that really brings out the gap between Israeli Jews and American Jews.”


While more than 60 percent of Jews in the United States identify with the Reform or Conservative movements, where women and men have equal standing in prayer and many feminists have adopted ritual garments, in Israel it is one in 10. Instead, about half call themselves secular, and experts say that most of those consider Orthodoxy as the true Judaism, feel alienated from holy sites like the Western Wall, and view a woman in a prayer shawl as an alien import from abroad.


(Jewish law requires only men to pray daily, though many women have taken on the obligation voluntarily. It also says women should not dress like men.)


“Secular Israelis do not see this as their problem; to them it’s a bunch of crazy American ladies,” said Shari Eshet, who represents the New York-based National Council of Jewish Women here. “It’s embarrassing for Israel, it’s embarrassing for Jews, and the American Jewish community is beginning to understand that it’s a slippery slope here.”


The increased agitation around the wall is part of a broader clash over Judaism and gender that has roiled Israel in recent months. Women have won lawsuits against segregation on buses and sidewalks imposed in religious neighborhoods. But a bus line recently stopped accepting advertisements with images of people after religious vandals routinely blacked out women’s faces in the name of modesty.


In January, speakers at a conference on health and Jewish law canceled their appearances because women were barred from the podium — a demand of the most Orthodox — while the chief rabbi of the air force quit after religious soldiers were not excused from events where women sang.


These controversies concern the imposition of Orthodox doctrine in secular spheres. More complicated are questions of how Judaism itself should be practiced. This spring, the Supreme Court ruled that the government must pay the salary of a Reform rabbi along with hundreds of Orthodox ones. A small group of Jerusalem restaurants has been seeking an alternative kosher certification system to the one run by the government’s rabbinical council.


“The next chapter of what it means to be a Jewish state is being defined right now,” said Elana Sztokman, the director of the Jewish Orthodox Feminist Alliance, who is writing a book that includes a chapter about Women of the Wall. “We have to figure out what does Israel want, what role do we really want religion to have in this state? And it’s happening on the backs of women.”


Irit Pazner Garshowitz and Myra Noveck contributed reporting.



This article has been revised to reflect the following correction:

Correction: December 23, 2012

An earlier version of this article incorrectly identified the Jewish Agency as an arm of the Israeli government.



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