An enzyme designed by players of the protein-folding game Foldit was better than anything scientists could come up with.Image: Foldit
Obsessive gamers' hours at the computer have now topped scientists' efforts to improve a model enzyme, in what researchers say is the first crowdsourced redesign of a protein.
The online game Foldit, developed by teams led by Zoran Popovic, director of the Center for Game Science, and?biochemist David Baker, both?at the University of Washington in Seattle, allows players to fiddle at folding proteins on their home computers in search of the best-scoring (lowest-energy) configurations.
The researchers have previously reported successes by Foldit players in folding proteins, but the latest work moves into the realm of protein design, a more open-ended problem. By posing a series of puzzles to Foldit players and then testing variations on the players' best designs in the lab, researchers have created an enzyme with more than?18-fold higher activity than the original. The work was published January 22 in?Nature Biotechnology.
"I worked for two years to make these enzymes better and I couldn't do it," says Justin Siegel, a post-doctoral researcher working in biophysics?in Baker's group. "Foldit players were able to make a large jump in structural space and I still don't fully understand how they did it."
The project has progressed from volunteers donating their computers' spare processing power for protein-structure research, to actively predicting protein structures, and now to designing new proteins. The game has 240,000 registered players, 2,200 of whom were active last week.
The latest effort involved an enzyme that catalyses one of a family of workhorse reactions in synthetic chemistry called Diels-Alder reactions. Members of this huge family of reactions are used throughout industry to synthesize everything from drugs to pesticides, but enzymes that catalyze Diels-Alder reactions have been elusive. In 2010, Baker and his team?reported that they had designed a functional Diels?Alderase computationally from scratch3, but, says Baker, "it wasn't such a good enzyme".?The binding pocket for the pair of reactants was too open and activity was low. After their attempts to improve the enzyme plateaued, the team turned to Foldit.
In one puzzle, the researchers asked users to remodel one of four amino-acid loops on the enzyme to increase contact with the reactants.?In another puzzle, players were asked for a design that would stabilize the new loop. The researchers got back nearly 70,000 designs for the first puzzle and 110,000 for the second, then synthesized a number of test enzymes based on the best designs, ultimately resulting in the final, 18-fold-more-active enzyme.
Science by intuition
"It's a refreshing twist on enzyme engineering," says Stefan Lutz, a chemist?at Emory University in Atlanta, Georgia, who was not involved in the research. "Using the Foldit players allows the researchers to use human intuition at a scale that is unprecedented."
Foldit allows people to explore more drastic changes to the protein than are possible using standard methods such as directed evolution ? in which a large pool of randomly mutated enzymes is screened for mutants that improve the original. These mutations are typically just amino-acid substitutions, not the 13-amino-acid addition the players came up with. Systematically testing a change of that size?would require testing astronomical numbers of proteins.
FRIDAY, Jan. 20 (HealthDay News) -- In too many cases, doctors aren't doing a good job of informing American women with early stage breast cancer about the disease or their options in terms of surgery, a new study suggests.
In the study, researchers at the University of North Carolina surveyed breast cancer survivors on their knowledge of the disease. Respondents typically answered only about half of the questions correctly, and less than half said their surgeons had even asked them about their personal preference for surgery -- a full mastectomy vs. breast-conserving lumpectomy -- prior to treatment.
"We found that breast cancer survivors had fairly major gaps in their knowledge about their surgical options, including about the implications for recurrence and survival," said study lead author Dr. Clara Lee, an associate professor of surgery and director of surgical research at the University of North Carolina School of Medicine in Chapel Hill.
The paper was published in the January issue of the Journal of the American College of Surgeons.
For the study, Lee and her colleagues sent surveys to 746 women who had undergone surgery for stage one or stage two breast cancer at one of four medical centers: the Dana-Farber Cancer Institute and the Massachusetts General Hospital in Boston; the University of California, San Francisco; and the University of North Carolina, Chapel Hill.
Among the 440 patients who responded to the survey, less than half (about 46 percent) knew that local recurrence risk is higher after breast-conserving surgery (lumpectomy) than after mastectomy, and only about 56 percent of women knew that survival rates are equivalent for both options.
The study also revealed that women who said they preferred mastectomy were less likely to have treatment that was in accordance with their goals. Lee said this was probably because "patients reported that their doctors were more likely to discuss breast conservation therapy and its advantages than mastectomy. And many women did not recall being asked for their preference. We know from other studies that doctors don't always know their patients' personal preferences, so they may not be fully aware when a woman truly prefers mastectomy."
The fact that less than half (48.6 percent) of the patients recalled being asked their preference was particularly concerning to Lee.
"It would be one thing if we were talking about decisions for which there is clearly a superior treatment, such as treatment for an inflamed gallbladder," Lee said. "In this case, it's reasonable and actually better for the surgeon to make a recommendation. But here we're talking about a decision where there is no medically right answer, and it really depends on the patient's preference. In that situation, it makes sense to ask the patient what she prefers."
Another breast cancer surgeon cautioned that the retrospective nature of the study (asking women to recall past events) and the fact that the women filled out the surveys an average of two and a half years following surgery makes it hard to draw firm conclusions.
"Clearly there are deficits in knowledge, but what we don't know for sure is if that's because the surgeon failed to convey this information, or the surgeon failed to convey it in a way that the patient could understand, or the patient has simply forgotten," said Dr. Leslie Montgomery, chief of breast surgery at Montefiore Medical Center in New York City.
"If anything, I'm actually surprised that the numbers were as good as they were," Montgomery added. "There's often a big difference between what a woman is told and what she actually absorbs at a time when she is so emotionally distressed."
Montgomery believes the study is valuable, however, because it "helps identify the scope of the problem" and will be useful for designing future prospective trials.
"As surgeons, we really need to make sure we convey the proper information to a woman at what is probably one of the most stressful times in her life," Montgomery said.
More information
Find out more about surgical options for treating breast cancer at the American Cancer Society.
In Hawaii on Thursday, Rihanna ditched the full-body wetsuit and hit the waves, surfboard in tow, while rocking a slinky black g-string bikini.
PHOTOS: Rihanna's sexiest, craziest outfits
But the 23-year-old clearly had no intention of catching some surf and instead, put her assets on full display while lounging on her stomach atop the surfboard, done up in a cherry red lipstick, large gold hoop earrings, layers of matching necklaces and bracelets, and her hair styled in a messy 'do.
PHOTOS: Rihanna, then and now!
The Barbados beauty has been showing some major skin since arriving on the island last Saturday. Case in point: the "We Found Love" singer proudly shared a Twitpic of her working out on an elliptical machine while wearing just a tiny white bikini.
Perhaps the scantily-clad singer is showing off her dangeous curves in hopes that her ex-beau Chris Brown, who she's been seretly seeing, will see them?
PHOTOS: Rihanna and Chris' controversial romance
In the latest issue of Us Weekly, on stands now, a confidant of Brown's tells Us that the two have been known to "meet up casually," adding, "She comes to see him anytime she's in L.A."
"Rihanna loves to live dangerously, and talking to and hooking up with Chris is all part of that," adds a Rihanna insider.
Get more Us! Follow us on Twitter, Friend us on Facebook, Subscribe to Us Weekly
ABSOLUTELY. Those that have nothing to hide, hide nothing.
51%
173872
NO. We're still individuals entitled to privacy and we trust each other.
49%
VoteTotal Votes: 1044
By Athima Chansanchai
Just how much do you trust your spouse or partner? Enough to share passwords? For some, passwords are the final frontier of privacy not only in financial matters, but in social media and email correspondence. But for others, there are no secrets when you're in a relationship?? even risking the potential payback should a break-up sever the happy union.
The New York Times tells us about an "intimate custom" writer Matt Ritchel says is happening between teens in love: "sharing their passwords to email,?Facebook?and other accounts." The desire to be one even extends, the article claims, to couples creating identical passwords and letting each other read private emails and texts.?
For some, it takes a court order to share so much.
But for others, it's imperative to know each other's passwords as part of an open, healthy and fully functioning relationship. Sometimes this comes after a loss of trust, as when one partner has cheated on the other. On the Surviving Infidelity website, where more than 34,000 members have exchanged stories of betrayal and support one another in the forums, there is a saying that becomes a mantra for many of them: "Those who have nothing to hide, hide nothing." To that end, nothing is private anymore in order to facilitate healing for the offended party.?
In this philosophy, those who have been unfaithful should share (or make open and available) not only passwords to their email accounts and Facebook, but also the contents of their text messages, phone logs, work and travel itineraries "without qualms."
Many in those forums mention how finding secret Facebook and email correspondences led to the big reveal of infidelity in their marriages and relationships, and we've seen surveys that attribute at least some fault in Facebook, though an informal poll we took at the end of year showed that nearly half of the 876 votes attributed the demise of their marriages with other factors. But 34 percent did blame Facebook.
Some of the teens in the New York Times article who opened themselves up were dealt a nasty lesson in human nature when their not-so-better halves decided to use the passwords in retaliation for perceived wrongs. The Times listed some examples:
The stories of fallout include a spurned boyfriend in junior high who tries to humiliate his ex-girlfriend by spreading her e-mail secrets; tensions between significant others over scouring each other?s private messages for clues of disloyalty or infidelity; or grabbing a cellphone from a former best friend, unlocking it with a password and sending threatening texts to someone else.
Take our poll and let us know if couples should share passwords.
More stories:
Check out Technolog on?Facebook, and on Twitter, follow?Athima Chansanchai, who is also trying to keep her head above water in the?Google+?stream.
As you know, preparation is the key to doing well on a job interview and hirers tend to ask the same kinds of questions. This job interview one-sheeter is like a CliffsNotes for getting your strategic answers together.
Shared by Jenny Blake of LifeAfterCollege, the Google Docs template covers seven key questions or topic areas for you to bullet-point your examples, including how you're suited for the position, what your weaknesses are, what excites you, challenges you've overcome, and goals you have in the future. There's an area for questions you have for the company (such as issues or challenges about the job) and other notes (perhaps personal sound bites would be good here).
Just filling out the sheet can help you prepare, but you can also bring it to your interview and quickly glance at it while waiting (nice to have on you just in case).
Job Interview One-Sheeter | Google Docs via Wise Bread
Mysterious flotsam in Gulf of Mexico came from Deepwater Horizon rig, WHOI study findsPublic release date: 19-Jan-2012 [ | E-mail | Share ]
Contact: WHOI Media Relations media@whoi.edu 508-289-3340 Woods Hole Oceanographic Institution
Tracking debris from damaged oil rigs can help forecast coastal impacts in the future
Shortly after the Deepwater Horizon disaster, mysterious honeycomb material was found floating in the Gulf of Mexico and along coastal beaches. Using state-of-the-art chemical forensics and a bit of old-fashioned detective work, a research team led by scientists at Woods Hole Oceanographic Institution (WHOI) confirmed that the flotsam were pieces of material used to maintain buoyancy of the pipe bringing up oil from the seafloor.
The researchers also affirmed that tracking debris from damaged offshore oil rigs could help forecast coastal pollution impacts in future oil spills and guide emergency response effortsmuch the way the Coast Guard has studied the speed and direction of various floating debris to guide search and rescue missions. The findings were published Jan. 19 in Environmental Research Letters.
On May 5, 2010, 15 days after the Deepwater Horizon explosion, oceanographer William Graham and marine technicians from the Dauphin Island Sea Lab were working from a boat about 32 miles south of Dauphin Island, Ala., when they saw a 6-mile-long, east-west line containing more than 50 pieces of white material interspersed with sargassum weed. The porous material was uniformly embedded with black spheres about a centimeter in diameter. No oil slick was in sight, but there was a halo of oil sheen around the honeycomb clumps.
Two days later, the researchers also collected similar samples about 25 miles south of Dauphin Island. Nobody knew what the material was, with some hypothesizing at first that it could be coral or other substance made by marine plants or animals. Graham sent samples to WHOI chemist Chris Reddy, whose lab confirmed that the material was not biological. But the material's source remained unconfirmed.
In January 2011, Reddy and WHOI researcher Catherine Carmichael, lead author of the new study, collected a piece of the same unknown material of Elmer's Beach, Grand Isle, La. In April, 2011, they found several large pieces, ranging from 3 to 10 feet, of the honeycomb debris on the Chandeleur Islands off Louisiana.
Oil on all these samples was analyzed at WHOI using comprehensive two-dimensional gas chromatography. The technique identifies the thousands of individual chemical compounds that comprise different oils from different reservoirs. The chemistry of the oil on the debris matched that of oil sampled directly from the broken pipe from the Macondo well above the Deepwater Horizon rig.
In addition, one piece of debris from the Chandeleur Islands retained a weathered red sticker that read "Cuming" with the numbers 75-1059 below it. Reddy found a company called Cuming Corporation in Avon, Mass., which manufactures syntactic foam flotation equipment for the oil and gas industry. He e-mailed photos of the specimen to the company, and within hours, a Cuming engineer confirmed from the serial number that the foam came from a buoyancy module from Deepwater Horizon.
"We realized that the foam and the oil were released into the environment at the same time," Reddy said. "So we had a unique tracer that was independent of the oil itself to chronicle how oil and debris drifted out from the spill site."
The scientists overlaid the locations where they found honeycomb debris on May 5 and 7 with daily forecasts produced by the National Oceanic and Atmospheric Administration (NOAA) of the trajectory of the spreading oil slick. NOAA used a model that incorporated currents and wind speeds, along with data from planes and satellites. On both days, the debris was about 6.2 miles ahead of the spreading slick.
The explanation, the scientists said, is the principle of leeway, a measure of how fast wind or waves push materials. The leeway for fresh oil is 3 to 3.3 percent, but the scientists suspected that "the protruding profile of the buoyant material" acted acting like a sail, allowing wind to drive it faster than and ahead of the floating oil.
In this case, the flotsam served as a harbinger for the oncoming slick, but because different materials can have different leeways, oil spill models may not accurately forecast where oiled debris will head. "Even a small deviation in leeway can, over time, results in significant differences in surface tracks because of typical wind fields," the scientists wrote.
The Coast Guard has a long history of calculating the leeway of various materials, from life jackets to bodies of various sizes and weights, to improve forecasts of where the materials would drift if a ship sank or a plane crashed into the sea. But calculating leeways has not been standard practice in oil spills.
"We never had solid data to make the case until this study," said Merv Fingas, who tracked oil spills for more than 38 years for Environment Canada, which is equivalent to the U.S. Environmental Protection Agency.
"These results," the study's authors wrote, "provide insights into the fate of debris fields deriving from damaged marine materials and should be incorporated into emergency response efforts and forecasting of coastal impacts during future offshore oil spills."
###
This research was funded by the National Science Foundation.
The Woods Hole Oceanographic Institution is a private, independent organization in Falmouth, Mass., dedicated to marine research, engineering, and higher education. Established in 1930 on a recommendation from the National Academy of Sciences, its primary mission is to understand the ocean and its interaction with the Earth as a whole, and to communicate a basic understanding of the ocean's role in the changing global environment.
[ | 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.
Mysterious flotsam in Gulf of Mexico came from Deepwater Horizon rig, WHOI study findsPublic release date: 19-Jan-2012 [ | E-mail | Share ]
Contact: WHOI Media Relations media@whoi.edu 508-289-3340 Woods Hole Oceanographic Institution
Tracking debris from damaged oil rigs can help forecast coastal impacts in the future
Shortly after the Deepwater Horizon disaster, mysterious honeycomb material was found floating in the Gulf of Mexico and along coastal beaches. Using state-of-the-art chemical forensics and a bit of old-fashioned detective work, a research team led by scientists at Woods Hole Oceanographic Institution (WHOI) confirmed that the flotsam were pieces of material used to maintain buoyancy of the pipe bringing up oil from the seafloor.
The researchers also affirmed that tracking debris from damaged offshore oil rigs could help forecast coastal pollution impacts in future oil spills and guide emergency response effortsmuch the way the Coast Guard has studied the speed and direction of various floating debris to guide search and rescue missions. The findings were published Jan. 19 in Environmental Research Letters.
On May 5, 2010, 15 days after the Deepwater Horizon explosion, oceanographer William Graham and marine technicians from the Dauphin Island Sea Lab were working from a boat about 32 miles south of Dauphin Island, Ala., when they saw a 6-mile-long, east-west line containing more than 50 pieces of white material interspersed with sargassum weed. The porous material was uniformly embedded with black spheres about a centimeter in diameter. No oil slick was in sight, but there was a halo of oil sheen around the honeycomb clumps.
Two days later, the researchers also collected similar samples about 25 miles south of Dauphin Island. Nobody knew what the material was, with some hypothesizing at first that it could be coral or other substance made by marine plants or animals. Graham sent samples to WHOI chemist Chris Reddy, whose lab confirmed that the material was not biological. But the material's source remained unconfirmed.
In January 2011, Reddy and WHOI researcher Catherine Carmichael, lead author of the new study, collected a piece of the same unknown material of Elmer's Beach, Grand Isle, La. In April, 2011, they found several large pieces, ranging from 3 to 10 feet, of the honeycomb debris on the Chandeleur Islands off Louisiana.
Oil on all these samples was analyzed at WHOI using comprehensive two-dimensional gas chromatography. The technique identifies the thousands of individual chemical compounds that comprise different oils from different reservoirs. The chemistry of the oil on the debris matched that of oil sampled directly from the broken pipe from the Macondo well above the Deepwater Horizon rig.
In addition, one piece of debris from the Chandeleur Islands retained a weathered red sticker that read "Cuming" with the numbers 75-1059 below it. Reddy found a company called Cuming Corporation in Avon, Mass., which manufactures syntactic foam flotation equipment for the oil and gas industry. He e-mailed photos of the specimen to the company, and within hours, a Cuming engineer confirmed from the serial number that the foam came from a buoyancy module from Deepwater Horizon.
"We realized that the foam and the oil were released into the environment at the same time," Reddy said. "So we had a unique tracer that was independent of the oil itself to chronicle how oil and debris drifted out from the spill site."
The scientists overlaid the locations where they found honeycomb debris on May 5 and 7 with daily forecasts produced by the National Oceanic and Atmospheric Administration (NOAA) of the trajectory of the spreading oil slick. NOAA used a model that incorporated currents and wind speeds, along with data from planes and satellites. On both days, the debris was about 6.2 miles ahead of the spreading slick.
The explanation, the scientists said, is the principle of leeway, a measure of how fast wind or waves push materials. The leeway for fresh oil is 3 to 3.3 percent, but the scientists suspected that "the protruding profile of the buoyant material" acted acting like a sail, allowing wind to drive it faster than and ahead of the floating oil.
In this case, the flotsam served as a harbinger for the oncoming slick, but because different materials can have different leeways, oil spill models may not accurately forecast where oiled debris will head. "Even a small deviation in leeway can, over time, results in significant differences in surface tracks because of typical wind fields," the scientists wrote.
The Coast Guard has a long history of calculating the leeway of various materials, from life jackets to bodies of various sizes and weights, to improve forecasts of where the materials would drift if a ship sank or a plane crashed into the sea. But calculating leeways has not been standard practice in oil spills.
"We never had solid data to make the case until this study," said Merv Fingas, who tracked oil spills for more than 38 years for Environment Canada, which is equivalent to the U.S. Environmental Protection Agency.
"These results," the study's authors wrote, "provide insights into the fate of debris fields deriving from damaged marine materials and should be incorporated into emergency response efforts and forecasting of coastal impacts during future offshore oil spills."
###
This research was funded by the National Science Foundation.
The Woods Hole Oceanographic Institution is a private, independent organization in Falmouth, Mass., dedicated to marine research, engineering, and higher education. Established in 1930 on a recommendation from the National Academy of Sciences, its primary mission is to understand the ocean and its interaction with the Earth as a whole, and to communicate a basic understanding of the ocean's role in the changing global environment.
[ | 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.
Original Oldboy helmer Chan-wook Park is making his U.S. directorial debut with Stoker, which is due to hit theaters before the end of 2012. He will also lend a helping hand to fellow Korean filmmaker Joon-ho Bong on the latter?s own first English-language project, titled Snow Piercer (which Park will produce).
Captain America himself, Chris Evans, is set to headline the movie, which is based on Bong?s screenplay. Evans looks to be in good company, seeing how the likes of award-winners Jamie Bell and Tilda Swinton are currently in the midst of negotiations to co-headline Bong?s latest cinematic tale.
Bong spoke to Collider (all the way back in 2009) about Snow Piercer, which he says is based on a French graphic novel titled ?Le Transperceneige.? Variety has also confirmed that the apocalyptic story takes place ?in a new ice age? and revolves around a pack of survivors who are forced to live together on a train. However, even with the world?s end upon them, differences in class and social standing still separate the main characters, making it all the more difficult for them to peacefully co-exist with their fellow passengers.
That sounds like the promising setup for a darker character study from Bong, who?s best known in the States for his tongue-in-cheek cult classic monster horror flick, The Host.?His status as a director has only improved since that 2006 release, thanks to his acclaimed 2009 crime drama Mother, so it?s no surprise that Bong?s first foray into U.S. filmmaking is attracting some big name talent (much like Park?s Stoker?has).
Bong's 'The Host' weaves together horror-comedy with social commentary
Evans, with this move, continues to balance out his Marvel comic book blockbuster roles with more personal indie titles, as he did in 2011 with appearances in The First Avenger and the drug drama Puncture ? and will do so again the near future, with roles in The Avengers, The Iceman, and now Snow Piercer. It?s a smart strategy, on Evan?s part ? one that should also allow him to avoid running in circles as an actor (re: end up being typecast).
Bell actually takes a similar approach to selecting his roles as Evans, seeing how the former also likes to balance out parts in big-budget fare such as King Kong and The Adventures of Tintin with roles in more personable productions like?Retreat and Jane Eyre. Swinton, of course, generally sticks to non-mainstream parts (her role in the Chronicles of Narnia movies aside) as evidenced by her much-buzzed-about recent turn in We Need to Talk About Kevin and an upcoming role in Wes Anderson?s Moonrise Kingdom.
That?s all to say: there?s an excellent cast being assembled for Bong?s?Snow Piercer, which is tentatively expected to begin principal photography by March 2012 ? so, dedicated movie geeks, you may want to keep an eye out for this one.
As you know, preparation is the key to doing well on a job interview and hirers tend to ask the same kinds of questions. This job interview one-sheeter is like a CliffsNotes for getting your strategic answers together. ![[ Back to EurekAlert! ]](https://lh3.googleusercontent.com/blogger_img_proxy/AEn0k_vQs2cSbj9oMsJiDDPj60U6MdPnhQA97dDa4ZitQ0w6LZ7Uw_tmFL9bwhmPARgxihoUc-8aztm-Sg3OgyNnZHb8qpEmGXfE0b3RsKxnWQQ=s0-d){kind=small}
Public release date: 19-Jan-2012
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