New kind of antibiotic may be more effective at fighting tuberculosis, anthrax, and other diseases

June 3, 2013 ? Diseases such as tuberculosis, anthrax and shigellosis -- a severe food-borne illness -- eventually could be treated with an entirely new and more-effective kind of antibiotic, thanks to a team of scientists led by Kenneth Keiler, an associate professor of biochemistry and molecular biology at Penn State. The team describes 46 previously untested molecules that target and disrupt an important step in the process of protein synthesis in bacteria, thereby making the bacteria incapable of replicating.

This important step, known as "trans-translation," is a quality-control mechanism that is found in all species of bacteria. "If you imagine a bacterium's protein-synthesis pathway as a factory assembly line, trans-translation is responsible for keeping the assembly line moving," Keiler said. "Faulty messenger RNA -- which conveys genetic information from DNA to proteins -- can block the bacterium's synthesis machinery. But the trans-translation mechanism removes these blockages from the assembly line, thereby keeping the bacterium's system running smoothly." Keiler explained. "The bacterium would not be able to synthesize the proteins that it needs for survival without the trans-translation mechanism." Plants and animals, do not seem to have or need this trans-translation process.

Keiler discovered the previously unknown trans-translation process in bacteria when he was a graduate student in 1996. Since then, he has been working to find molecules capable of disrupting this part of bacteria's protein-synthesis pathway. "The idea is to throw a wrench into the protein-synthesis assembly line and prevent bacterial organisms from making copies of themselves," Keiler said.

To discover which small molecules might be capable of disrupting trans-translation, the team began with a process called high-throughput screening -- a method of trying out many thousands of small molecules with the hope of discovering one or more that might be effective at combatting certain pathogens. "Our team tested about 663,000 different molecules against a strain of E. coli bacteria and monitored how they were affecting its trans-translation process," Keiler said. At the end of this phase of testing, Keiler and his team had found 46 different molecules that appeared to be effective in disrupting the trans-translation process.

The next step was to test these molecules' performance in another genus of bacteria (Shigella) that is known to cause food poisoning. This genus is related to Salmonella and to the organism that causes anthrax (Bacillus anthracis), which sometimes can be lethal in humans and other animals. "Of the 46 molecules that were shown to affect trans-translation, one called KKL-35 jumped out as the most promising," Keiler said. "We found that the KKL-35 molecule inhibits the growth of very distantly related bacteria, and this suggests that it may have antibiotic activity against a very broad spectrum of species."

As for the Shigella and Bacillus anthracis bacteria, Keiler said his team was able to show that, "in the presence of the KKL-35 molecule, these cells died specifically because the molecule halted the trans-translation process." Keiler's team also found that, compared with currently used tuberculosis drug therapies, the KKL-35 molecule was 100-times more effective at inhibiting the growth of the strain of bacteria that causes tuberculosis (Mycobacterium tuberculosis).

Keiler added that one of the most exciting features of an antibiotic designed from the KKL-35 molecule is that drug resistance is not very likely to develop in mutant strains of the targeted bacteria. "In our laboratory experiments, we found no mutant strains that were resistant to KKL-35," Keiler said. "Resistant mutants probably could evolve eventually, but at least it looks like it will be very difficult. That means resistant mutants might be slow to arise and spread."

The research was funded by the National Institutes of Health.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/BOWhk8G8H6k/130603163809.htm

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Late Wall Street rally shores up markets

An investor speaks to another at a private securities company Tuesday, June 4, 2013, in Shanghai, China. Asian stock markets were volatile Tuesday after a report showed manufacturing activity in the U.S. fell to its lowest level in four years. Losses were limited, however, because investors believe negative reports make it more likely for the Federal Reserve to stick with its economic stimulus programs. (AP Photo)

An investor speaks to another at a private securities company Tuesday, June 4, 2013, in Shanghai, China. Asian stock markets were volatile Tuesday after a report showed manufacturing activity in the U.S. fell to its lowest level in four years. Losses were limited, however, because investors believe negative reports make it more likely for the Federal Reserve to stick with its economic stimulus programs. (AP Photo)

LONDON (AP) ? Markets remained volatile Tuesday as investors focused on U.S. economic indicators and whether they make the Federal Reserve more or less likely to change the terms of its monetary stimulus.

For the past few weeks, market sentiment has been largely dependent on the vagaries of the U.S. economic data ? figures indicating that the U.S. economy is growing strongly has been met with concern among stock investors in particular, while any weakness has spurred buying.

On Monday, a disappointing manufacturing survey from the Institute for Supply Management was cheered as investors concluded that it was now less likely that the Fed would reduce the amount of financial assets it buys as part of a strategy to shore up the U.S. economic recovery. The stimulus has been one of the main reasons why many stock indexes have hit record highs, so investors have been viewing a possible withdrawal with concern.

Wall Street enjoyed a strong rally at the close on Monday and that positive sentiment continued, albeit at a less marked pace, into European and Asian trading. Japanese shares, in particular, recovered some ground.

"A strong close in the U.S. trading session and the mild rebound in Japan's benchmark overnight have seen investors dip a cautious toe into European risk assets this morning," said Brenda Kelly, senior market strategist at IG.

In Europe, the FTSE 100 index of leading British shares was up 0.5 percent at 6,555 while Germany's DAX rose 0.3 percent to 8,312. The CAC-40 in France was 0.3 percent higher at 3,933.

Wall Street was poised for a flat opening following Monday's late advance, with both Dow futures and the broader S&P 500 futures down 0.1 percent.

Though Monday's ISM survey, which indicated that the manufacturing sector was contracting again, reined in expectations of a Fed policy change, there's a lot of economic data this week that could alter predictions again.

Tuesday is probably the lightest data day of the week, but the pace picks up on Wednesday with the ADP private payrolls report for May and the ISM's survey of activity in the services sector. Most important will be Friday's nonfarm payrolls report for May. The payrolls figures are usually the U.S. economic release with the greatest market impact.

"Markets seem to be dominated by flow and positioning ahead of the next batch of event risk tomorrow," said Adam Cole, an analyst at RBC Capital Markets.

It's also a big week in Europe, with the European Central Bank meeting to discuss the ailing eurozone economy and whether anything more needs to be done to get it growing again. The latest speculation in the markets is that the ECB will refrain from announcing any big new measures Thursday.

Ahead of the raft of economic news about to emerge, most currencies were stable. The euro was unchanged at $1.3075, while the dollar recouped some of the previous days' retreat against the yen, trading 0.5 percent higher at 100.52 yen.

The Australian dollar was in focus after the country's central bank opted against cutting interest rates again but hinted at further easing and voiced concern over the currency's strength. The Aussie dollar was down 1.1 percent at $0.9652, helping the country's main stock index post a modest 0.3 percent advance.

Elsewhere in Asia, Japan's Nikkei 225 index clawed back some of its prior session losses with a 2.1 percent gain to close at 13,533.76. Mainland Chinese shares fell for a fourth straight day, with the Shanghai Composite Index falling 1.2 percent to 2,272.42, its biggest loss in more than a month. Hong Kong's Hang Seng was nearly unchanged at 22,285.52.

Oil prices drifted lower, with the benchmark New York rate down 54 cents at $92.91 a barrel.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/f70471f764144b2fab526d39972d37b3/Article_2013-06-04-World%20Markets/id-869760a1d83b4ca3bafb8b7dd60e0ffc

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Environmentalists Unite in Quest to Fight Global Warming

The nation?s environmental leaders are mounting a double battle against global warming, and they see President Obama?s remaining time in the White House as critical in winning both of them.

In interviews with the leaders of seven major environmental organizations, they all indicated a sense of unity and urgency on rolling out regulations to control the greenhouse-gas emissions that scientists agree cause climate change and on blocking the Keystone XL pipeline, which would carry carbon-heavy oil sands 1,700 miles from Canada to the Gulf Coast.

?I was recently with my colleagues at a quarterly CEO meeting with different groups, and I would say I feel very strongly that we?re unified that these two things go hand in hand in an ask to the White House,? said Frances Beinecke, president of the Natural Resources Defense Council. ?They?re both very important to the community as a whole.?

The environmental chiefs don?t want one or the other. They want both. They?re lobbying Obama, who promised action on climate change in his second term but has yet to follow up, to both deny the pipeline and move quickly on Environmental Protection Agency regulations controlling carbon emissions. They reject the political theory conceived by some Democratic and Republican insiders throughout Washington that the White House may make a trade-off by approving the pipeline but simultaneously signaling bold action on climate change with EPA rules.

?I?m not going to weigh one against the other, not going to go there,? said Fred Krupp, who has been the president of the Environmental Defense Fund, one of the most influential environmental groups, for almost 30 years. ?It shouldn?t be one or the other. I think he should get both of them right.?

Krupp?s comments may surprise some in the environmental community, because EDF has been relatively quiet on the pipeline compared with other groups interviewed for this article, including NRDC, the League of Conservation Voters, the National Wildlife Federation, the Sierra Club, CREDO, and 350.org.

?I could imagine EDF making a trade-off, because they?ve been pretty quiet on the pipeline, and they have a history of making trade-offs,? said Michael Kieschnick, president and cofounder of CREDO Mobile, a wireless phone company that forcefully advocates for progressive causes, especially climate change.

In a mostly organic manner, the organizations have divided up the labor. Leading the way on the Keystone XL pipeline have been CREDO; 350.org, a global environmental group founded in 2007 by author Bill McKibben; and the Sierra Club. All three groups have pledged to carry out an act of civil disobedience (in other words: get arrested) to protest the project.

EDF and NRDC are especially focused on lobbying EPA to get going on what are poised to be the most complicated, most litigated, and most contentious regulations the agency has rolled out in its 43-year history.

?This is one issue where [Obama] has executive authority under the Clean Air Act, and our No. 1 ask is to get him to use that authority to reduce emissions from existing power plants,? Beinecke said. ?The single largest carbon-reduction potential is from the power-plant rule.?

CREDO?s Kieschnick acknowledged that EPA rules have a greater potential to cut carbon emissions than would denial of the Keystone XL pipeline.

?I would say that if you would add up all the regulations, all the coal regulations, mercury regulations, ozone, plus the new and existing [rules for carbon emissions], numerically they would have a bigger impact done correctly than a yes/no decision on Keystone,? he said.

Kieschnick has attended private events recently where he said he asked Obama directly about the pipeline and the EPA rules. On Keystone, the president told him he hasn?t made a decision. On pending rules controlling carbon emissions from new plants, Obama told him EPA will issue those rules. But when Kieschnick has asked the administration about the specific rules that will have the greatest impact?those targeting current power plants??you don?t get a useful answer,? he said. ?I don?t think they?re committed to issuing one on existing power plants.?

That?s the irony the community is facing. With scientists reporting last month that the planet has reached a grim milestone in the amount of carbon dioxide in the atmosphere, environmentalists are more united than ever behind their goals. And yet they face more political roadblocks than ever in Washington in getting something big done. Congress is gridlocked and is not poised to do anything significant on climate-change policy. Obama has been quiet in the first six months of his second term, after promising a lot.

?The president himself needs to become a much stronger voice on the urgency of this matter,? said Larry Schweiger, president and CEO of the National Wildlife Federation. ?Without that, I don?t think we?re going to get the kind of traction that we desperately need to get.?

Source: http://news.yahoo.com/environmentalists-unite-quest-fight-global-warming-132843706.html

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PFT: Jim Kelly has cancer in upper jaw

Getty Images

He has the best receiver in the NFL.? He?d apparently prefer to have the best cornerback.

Lions coach Jim Schwartz says cornerback is the hardest position in the NFL, or in any sport.

?It?s tough to play corner [in the NFL],? Schwartz recently said, via the team?s official website.? ?I think it?s probably the most difficult thing to do in all of sports.

?You have to run with world-class receivers, you?ve got to start backwards and they?re going forward.? They know where they?re running, you don?t.? You?ve got to be tough enough to take on pulling guards and running backs and skilled enough and fast enough to cover the elite athletes, you know, guys that are Olympic-caliber speed.?

(Deion Sanders thinks the comment about taking on pulling guards is funny.)

The trend is toward larger corners, something the Seahawks have pioneered.? The Lions now have four corners who are at least six feet tall.

?You don?t want to end up sacrificing speed, you don?t want to end up sacrificing toughness and change of direction.? I think that?s the balance that you have to play there,? Schwartz said.

If that?s the case, it seems like more teams would have been willing to trade for Darrelle Revis, and to give him $16 million per year on a pay-as-you-go contract.

And it seems like the Lions would have been more interested in taking a corner like Dee Milliner or D.J. Hayden with the fifth overall pick in the 2013 draft.

Source: http://profootballtalk.nbcsports.com/2013/06/03/jim-kelly-has-cancer-prognosis-for-recovery-is-good/related/

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Game Dev Tycoon Review ? GamingBolt.com: Video Game News ...

Game Dev Tycoon is a brilliant game. It?s fun, it?s addictive, it?s time consuming, and it has a great sense of humor. Building on the equally great Kairosoft developed Game Dev Story for iOS and Android, Game Dev Tycoon presents the player with some general insights into the game development process, and the backstage workings of the gaming industry that we all know and love. Oh, and it?s also inadvertently funny too, sometimes.

Game Dev Tycoon tasks the player with taking control of a startup back in the early 1980s, and develop games. At the beginning, you are a one man team working out of your garage, developing low profile games for PC and Commodore. Your options for developing games are severely limited too, as you can only develop text based games, or games with very basic graphics, and even more basic sound, in a limited set of genres, and on limited topics.

Over time, you research new genres and new topics, you research better graphics and better sound, you research new game making techniques such as branching dialogs, multiplayer, online play, achievements, voice acting, non linear story telling, and more. You create your own game engines to make the best games possible. You move from making games for primitive PCs to more modern ones, and games for consoles as well. You learn to market your games and generate hype. You create your own franchises. You learn to target them at specific audiences and demographics. You attend E3, you expand your team slowly by recruiting even more developers.

And eventually, you make your own console. You hold your own expos and conventions. You develop your own digital distribution service. You expand into AAA game development. The amount of stuff you can do, and the exhaustiveness of the choice available to you, the player, as well as the game?s recapitulation of the last thirty years of gaming history, along with its guesses as to what comes next, are incredible. I?ve mentioned things in broad strokes up there. There?s more, so much more. Game Dev Tycoon is an incredibly expansive game, and one that, unlike many other sim games, demands player agency and involvement.

The main ?story? portion of the game is thirty years- from the advent of basic computer gaming to the release of the Nintendo Wuu, Microsoft?s mBox Bext, and Sony?s PlaySystem 4. You are still free to play after that, but there won?t be any more story events, and any new console releases, or the like, for example, have to come from you. Which is just as well, because once those thirty years end, you get full control of the game.

What?s even better is the numerous references to the real gaming industry that the game is peppered with. From the names of the systems above (in addition to others like GameSphere, Master V, and Nuu), to the names of the companies (Nivtendo, Vonny, Vena, and Gommodore), to the frequent, often hilarious market reports we get (Market analysis indicates that the Gommodore 64?s success means the end of other PC manufacturers; we are hesitant about how good console gaming will ever catch on), to the discreet posters and memorabilia of real games such as Meat Boy, Journey, and?Pac-man?that are discreetly packed away in your offices, it?s great. Game Dev Tycoon works as much as a virtual record of the gaming industry so far as it works at being a great sim.

Of course, there are problems. The Mac version is broken, for instance, and after your expansion into the largest office, it simply crashes, and cannot be played again, unless the game is uninstalled and all local file are deleted. There is, of course, the abovementioned fact that this is not a very original game, and in fact is simply building on an excellent base provided by Kairosoft?s Game Dev Story. There is also the matter of the game?s sound and graphics, which are passable at best.

But on the whole, this is an incredible game, one that you will find yourself playing a lot, and for hours and hours and hours at a time. It?s great fun, it?s a wonderful commentary on the state of game development, and it?s just addictive as hell. For $8, you really cannot go wrong with Game Dev Tycoon, and this is a game that is heavily recommended to everybody.

This game was reviewed on PC.

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Source: http://gamingbolt.com/game-dev-tycoon-review

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Mosquitoes reared in cooler temperatures have weaker immune systems

June 3, 2013 ? Urban epidemics resulting from viral diseases, such as West Nile fever and chikungunya fever, are transmitted by infected mosquitoes.

According to Virginia Tech scientists, mosquitoes reared in cooler temperatures have weaker immune systems, making them more susceptible to dangerous viruses and more likely to transmit them to people.

The connection between temperature and the mosquito's immune system, published May 31 in PLOS Neglected Tropical Diseases, is significant in light of global climate change, said researchers Kevin Myles and Zach Adelman, associate professors of entomology in the College of Agriculture and Life Sciences, and affiliates of the Fralin Life Science Institute.

"Our data offers a plausible hypothesis for how changes in weather influence the transmission of these diseases and will likely continue to do so in the future," Myles said.

A variety of weather anomalies may occur with global changes in climate. However, predicting what these weather anomalies will be is difficult due to the enormous complexity involved. Nevertheless, the work of Myles and Adelman suggest that it would be unwise to focus solely on warmer temperatures when considering links between climate change and disease transmission.

"Mosquitoes like to breed and lay their eggs in dark, cool places because that means the water will last longer," Adelman said. "They don't lay their eggs in sunny spots because that will dry the water out in a day or two. Although this has been known of some time, we are just learning about its potential affects on the mosquito immune response. Hopefully, this information can be used to build better models that more correctly predict when we'll have disease transmission."

Current computational outbreak models consider such things as meteorological variables and human population indexes but have failed to consider the effect of temperature on mosquito immunity, he added. Specifically, Adelman and Myles found that the mosquito's RNA interference pathway is impaired when reared at cooler temperatures.

The rate of transmission of both diseases has increased with outbreaks occurring in unexpected places, such as the introductions of West Nile virus to New York in 1999, and chikungunya virus to Italy and France in 2007 and 2010.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/most_popular/~3/7v8wnBOM4dI/130603183210.htm

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Obama orders new economic sanctions on Iran

Iranian presidential candidate Ali Akbar Velayati, a former Foreign Minister, walks past a portrait of supreme leader Ayatollah Ali Khamenei at the conclusion of his press conference in Tehran, Iran, Monday, June 3, 2013. The 11th presidential election after Iran's 1979 Islamic Revolution will be held on June 14. (AP Photo/Ebrahim Noroozi)

Iranian presidential candidate Ali Akbar Velayati, a former Foreign Minister, walks past a portrait of supreme leader Ayatollah Ali Khamenei at the conclusion of his press conference in Tehran, Iran, Monday, June 3, 2013. The 11th presidential election after Iran's 1979 Islamic Revolution will be held on June 14. (AP Photo/Ebrahim Noroozi)

WASHINGTON (AP) ? Turning the screw on Iran and its nuclear program, the Obama administration imposed new sanctions Monday on Iran's currency and auto industry, seeking to render Iranian money useless outside the country and to cut off the regime from critical revenue sources.

The executive order from President Barack Obama broadens what is already a concerted and multifaceted sanctions campaign aimed at crippling Iran's economy, forcing it to comply with international demands that it prove its nuclear program is peaceful. The U.S. believes Iran is working to develop nuclear weapons, a charge that Iran denies.

Officials described the move as part of a dual-track effort to offer meaningful negotiations to the Iranian regime while continually upping the economic stakes.

"Even as we intensify our pressure on the Iranian government, we hold the door open to a diplomatic solution that allows Iran to rejoin the community of nations if they meet their obligations. However, Iran must understand that time is not unlimited," said White House press secretary Jay Carney, adding that more sanctions would be levied if the regime doesn't change course.

The new sanctions marked the first time Iran's currency, the rial, has been targeted directly with sanctions, the White House said. The sanctions apply to foreign financial institutions that purchase or sell significant amounts of the rial, as well as to those who hold significant amounts of the rial in accounts outside Iran.

Senior administration officials said the sanctions were designed to make the rial essentially unusable outside of Iran. The hope is that banks and businesses holding Iranian currency will dump the funds, making the rial weaker. The value of the rial has dropped by half since the start of 2012, the White House said.

Officials would not specify what constitutes a "significant" transaction. The officials were not authorized to speak on the record about the sanctions and spoke on condition of anonymity.

Another set of sanctions will target those who enable Iran's auto manufacturing sector by banning the sale or transfer of goods or services to be used in Iran's auto sector. Officials said the auto sector is a key source of revenue for the regime. Many of the auto parts and components from subsidiaries are dual-use and can be used in centrifuges or missiles.

Also subject to penalties will be anyone who provides material support to Iranians and others who have been blacklisted under previous U.S. sanctions. An exception will be made for some activities related to a pipeline project to move natural gas from Azerbaijan to Europe and Turkey.

The appetite has been growing on Capitol Hill for even tougher measures against Iran, fueled in part by lawmakers' concerns about key U.S. ally Israel, which considers a nuclear-armed Iran to be an existential threat. Last month the House Foreign Affairs Committee approved legislation that would impose even tougher economic sanctions against Tehran, while the Senate resolved the U.S. should back Israel if it's forced to take military action against Iran.

"The clock is clearly ticking," Secretary of State John Kerry said last month on a visit to Israel.

Harsher steps to isolate Iran were on the agenda Tuesday at a Senate Banking Committee hearing, where officials from the Treasury, Commerce and State departments were set to testify. An amendment being pushed by two of the panel's members, Sens. Joe Manchin, D-W.Va., and Mark Kirk, R-Ill., would go even further than Monday's announcement by targeting all Iranian foreign assets overseas ? such as euros Tehran might be holding in Japan.

The U.S. has already targeted other major sectors, most prominently Iranian oil exports, and last week targeted Iranian petrochemicals ? the largest source of funding for Iran's nuclear program after oil. Although Iranian officials have tried to downplay the effectiveness of the U.S. efforts, the Obama administration says they have had crippling effects. Crude oil production in Iran has fallen about 700,000 barrels per day since 2012, the White House said last week, and exports have dropped even more dramatically, costing Iran about $3 billion to $5 billion in revenue.

The damage inflicted to Iran's economy, while aimed at undermining the regime, has had inevitable consequences for the Iranian public, forcing the U.S. to strike a careful balance between isolating Iran's hard-line government and making life uncomfortable for those who live under its rule. To that end, the U.S. last week eased restrictions on exports of advanced communications equipment to Iranian civilians, aiming to help Iranians interact with the outside world and shed light on what U.S. officials described as the regime's oppressive attempts to stifle dissent.

The new round of sanctions comes at a politically charged moment in Iran, where the effects of U.S. sanctions have been a major issue ahead of the June 14 election to choose a replacement for term-limited President Mahmoud Ahmadinejad. Senior administration officials said the timing of the sanctions was not related to the upcoming elections.

___

Associated Press writer Donna Cassata contributed to this report.

___

Reach Josh Lederman on Twitter at http://twitter.com/joshledermanAP

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/89ae8247abe8493fae24405546e9a1aa/Article_2013-06-03-US-Iran%20Sanctions/id-e685df35f5764ce893dca5816f9e06f3

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