Structural studies of a toxin from Bacillus cereus that causes diarrhea

Jan. 4, 2013 ? Food poisoning caused by Bacillus cereus can lead to diarrhea which is probably caused by a 3-component toxin which is produced by this bacteria strain and which perforates and kills cells. New doctoral research has revealed one of the protein structures of this toxin and has led to a better understanding of the mechanisms behind multi-component, pore-forming toxins. These findings can enhance food safety.

Bacteria produce toxins in order to defend themselves and to gain nourishment. Pore-forming toxins make up about a third of all bacterial toxins. These toxins kill cells by making holes in the cell walls, so causing leakages and swelling which in turn leads to the disintegration of the cells. The most common pore-forming toxins consist of one protein and in some special cases, of two proteins.

Toxins which consist of three proteins (3-component) are extremely rare. The bacterium Bacillus cereus produces two such 3-component toxins. One of them is non-hemolytic enterotoxin, also known as Nhe. It is believed that this toxin is the major food poisoning toxin produced by B. cereus. It is found in all B. cereus strains that cause food poisoning and in nearly all other B. cereus strains. The three proteins in the Nhe toxin are called NheA, NheB and NheC.

In the course of her doctoral research, Danh Phung discovered the crystalline structure of one of the proteins in the Nhe toxin: NheA. This protein is the least studied of this toxin complex, but its presence is essential in order to achieve full cellular toxicity and pore formation. Phung's study is also the first to show that the Nhe proteins form structures resembling pores.

The way the Nhe toxin works is not fully understood. Phung showed that NheB, which is believed to be the most important protein in this toxin complex, forms pore-like structures of itself and produces large amounts of molecules by means of an artificial cell membrane, for example a lipid. These findings indicate that the NheB protein undergoes structural changes before the pore-forming process, which involves the other Nhe-proteins, begins.

Danh Phung carried out her doctoral research at the Norwegian School of Veterinary Science in collaboration with the Sir Hans Krebs Institute at the University of Sheffield in the UK.

M.Sc. Danh Phung defended her doctoral research on 18^th December 2012 at the Norwegian School of Veterinary Science (NVH) with a thesis entitled "Structure and mode of action on the Nhe enterotoxin from Bacillus cereus."

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Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/rDgRGrOL1AU/130104083105.htm

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$175k settlement reached after resource officer fatally shot stu - WCSC

MYRTLE BEACH, SC (WMBF) - A settlement has been reached in the lawsuit brought against Horry County Schools and Horry County Police by the family of Trevor Varinecz.

Trevor Varinecz died in October of 2009 after then Carolina Forest High School School Resource Officer Marcus Rhodes shot him.

Police investigations cleared Rhodes, and no charges have been filed against him.

However, Varinecz's parents decided to sue Rhodes, the high school, Horry County Schools and the Horry County Police Department claiming Rhodes did not have the proper training to prevent the death of their son.

In November, Officer Rhodes asked for a summary judgment saying he was acting in self-defense.

The court document just filed on Thursday, Nov. 15 has details of what happened that day that have not been released until now.

Rhodes says Varinecz came into his office with a bayonet and stabbed him in the back seven times.

Rhodes claims Varinecz would not drop his knife, and Rhodes was scared he was losing control of the situation, adding that he believed Varinecz would grab his gun.

That's when Rhodes fired 10 shots at Varinecz, killing him. As he was dying Varinecz said, "Thank you, sir, Thank you."

Investigators found a note in Varinecz's pocket that directed them to a suicide note on his personal computer.

The wrongful death lawsuit was settled on Dec. 28. The Carolina Forest Chronicle reports the Varinecz family will receive a settlement of $175,000.

That settlement is divided in to two equal payment of $87,500, one for the wrongful death cause of action and the other for "conscious pain and suffering," according to the settlement.

Officer Rhodes and a former counselor for Carolina Forest High School were dismissed from the lawsuit prior to this settlement, leaving the payment to be divided by the SC Department of Education, Horry County Schools, Horry County Police and Carolina Forest High School.

All four defendants are insured by SC Insurance Reserve Fund.

The terms of the settlement state the Varinecz family cannot bring any further legal action against these defendants.

Copyright 2013 WMBF News. All rights reserved.

Source: http://www.live5news.com/story/20492803/sro-seeks-end-to-trevor-varinecz-lawsuit

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Indian court to rule on generic drug industry

NEW DELHI (AP) ? From Africa's crowded AIDS clinics to the malarial jungles of Southeast Asia, the lives of millions of ill people in the developing world are hanging in the balance ahead of a legal ruling that will determine whether India's drug companies can continue to provide cheap versions of many life-saving medicines.

The case ? involving Swiss drug maker Novartis AG's cancer drug Glivec ? pits aid groups that argue India plays a vital role as the pharmacy to the poor against drug companies that insist they need strong patents to make drug development profitable. A ruling by India's Supreme Court is expected in early 2013.

"The implications of this case reach far beyond India, and far beyond this particular cancer drug," said Leena Menghaney, from the aid group Doctors Without Borders. "Across the world, there is a heavy dependence on India to supply affordable versions of expensive patented medicines."

With no costs for developing new drugs or conducting expensive trials, India's $26 billion generics industry is able to sell medicine for as little as one-tenth the price of the companies that developed them, making India the second-largest source of medicines distributed by UNICEF in its global programs.

Indian pharmaceutical companies such as Cipla, Cadila Laboratories and Lupin have emerged over the past decade as major sources of generic cancer, malaria, tuberculosis and AIDS drugs for poor countries that can't afford to pay Western prices.

The 6-year-old case that just wrapped up in the Supreme Court revolves around a legal provision in India's 2005 patent law that is aimed at preventing companies from getting fresh patents for making only minor changes to existing medicines ? a practice known as "evergreening."

Novartis' argued that a new version of Glivec ? marketed in the U.S. as Gleevec ? was a significant change from the earlier version because it was more easily absorbed by the body.

India's Patent Controller turned down the application, saying the change was an obvious development, and the new medicine was not sufficiently distinct from the earlier version to warrant a patent extension.

Patient advocacy groups hailed the decision as a blow to "evergreening."

But Western companies argued that India's generic manufacturers were cutting the incentive for major drug makers to invest in research and innovation if they were not going to be able to reap the exclusive profits that patents bring.

"This case is about safeguarding incentives for better medicines so that patients' needs will be met in the future," says Eric Althoff, a Novartis spokesman.

International drug companies have accused India of disregarding intellectual property rights, and have pushed for stronger patent protection that would weaken India's generics industry.

Earlier this year, an Indian manufacturer was allowed to produce a far cheaper version of the kidney and liver cancer treatment sorefinib, manufactured by Bayer Corp.

Bayer was selling the drug for about $5,600 a month. Natco, the Indian company, said its generic version would cost $175 a month, less than 1/30th as much. Natco was ordered to pay 6 percent in royalties to Bayer.

Novartis says the outcome of the new case will not affect the availability of generic versions of Glivec because it is covered by a grandfather clause in India's patent law. Only the more easily absorbed drug would be affected, Althoff said, adding that its own generic business, Sandoz, produces cheap versions of its drugs for millions across the globe.

Public health activists say the question goes beyond Glivec to whether drug companies should get special protection for minor tweaks to medicines that others could easily have uncovered.

"We're looking to the Supreme Court to tell Novartis it won't open the floodgates and allow abusive patenting practices," said Eldred Tellis, of the Sankalp Rehabilitation Centre, a private group working with HIV patients.

The court's decision is expected to be a landmark that will influence future drug accessibility and price across the developing world.

"We're already paying very high prices for some of the new drugs that are patented in India," said Petros Isaakidis, an epidemiologist with Doctors Without Borders. "If Novartis' wins, even older medicines could be subject to patenting again, and it will become much more difficult for us in future to provide medicines to our patients being treated for HIV, hepatitis and drug resistant TB."

Source: http://news.yahoo.com/indian-court-rule-generic-drug-industry-074247945.html

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AT&T launches several more 4G LTE markets in Michigan

AT&T is continuing its nationwide 4G LTE rollout today with several new markets going live with the service. As was the case with Verizon before it, AT&T is reaching the point where it has expanded its network to many of the major markets in the U.S. and is now rolling out to some of the lesser populated areas. Users in the following markets in Michigan should see the service live now:

• Ann Arbor, Michigan
• Beverly Hills, Michigan
• Birmingham, Michigan
• Monroe County, Michigan
• Kent County, Michigan
• Ottowa County, Michigan

We'll start to see more and more of these small rollouts throughout 2013. Have any of you in these areas noticed AT&T LTE go live yet? Let us know in the comments.

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Source: http://feedproxy.google.com/~r/androidcentral/~3/B_OrS8uZc88/story01.htm

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Ad Agencies Are Angry At Facebook And Amazon ... - Business Insider

Good morning, AdLand. Here's what you need to know today:

Ad agencies are complaining that Facebook and Amazon's ad privacy program is costing them extra time and money, Ad Age reports.?The publishers both don't use Ad Choices, the program basically every media firm, ad data firm and ad network uses.

The U.S. Postal Service?picked UM to be its media agency.

Al Jazeera?is acquiring Current TV.

Dating site?Zoosk?has a pretty funny new commercial starring a heart puppet.

Now former Goodby Silverstein & Partners'?creative director Marty Senn has joined up with Carmichael Lynch as an ECD in Minneapolis.

These were the 20 most shared YouTube ads in December.

Digiday?looks at how agencies deal with young employees.

Phunwear?just acquired global independent mobile ad company TapIt Media Group for #23 million.

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Source: http://www.businessinsider.com/ad-agencies-are-angry-at-facebook-and-amazonthe-brief-2013-1

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How computers push on the molecules they simulate

Jan. 3, 2013 ? Because modern computers have to depict the real world with digital representations of numbers instead of physical analogues, to simulate the continuous passage of time they have to digitize time into small slices. This kind of simulation is essential in disciplines from medical and biological research, to new materials, to fundamental considerations of quantum mechanics, and the fact that it inevitably introduces errors is an ongoing problem for scientists.

Scientists at the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) have now identified and characterized the source of tenacious errors and come up with a way to separate the realistic aspects of a simulation from the artifacts of the computer method. The research was done by David Sivak and his advisor Gavin Crooks in Berkeley Lab's Physical Biosciences Division and John Chodera, a colleague at the California Institute of Quantitative Biosciences (QB3) at the University of California at Berkeley. The three report their results in Physical Review X.

"Our group uses a theoretical method called nonequilibrium statistical mechanics to study molecular machines, the protein complexes essential to processes like photosynthesis and DNA repair," says Sivak. "But when we applied common algorithms to model the behavior in biological molecules, we found persistent, significant errors in the simulation results."

Systems in equilibrium are relatively easy to simulate, but natural systems are often driven far from equilibrium by absorbing light, burning energy-dense chemical fuel, or other driving forces. Sivak, who recently joined the University of California at San Francisco as a Systems Biology Fellow, describes nonequilibrium statistical mechanics as "a way of understanding situations where conditions change abruptly and the system has to play catch-up," a kind of problem in which there are few exact analytical results.

How biological molecules move is hardly the only field where computer simulations of molecular-scale motion are essential. The need to use computers to test theories and model experiments that can't be done on a lab bench is ubiquitous, and the problems that Sivak and his colleagues encountered weren't new.

"A simulation of a physical process on a computer cannot use the exact, continuous equations of motion; the calculations must use approximations over discrete intervals of time," says Sivak. "It's well known that standard algorithms that use discrete time steps don't conserve energy exactly in these calculations."

One workhorse method for modeling molecular systems is Langevin dynamics, based on equations first developed by the French physicist Paul Langevin over a century ago to model Brownian motion. Brownian motion is the random movement of particles in a fluid (originally pollen grains on water) as they collide with the fluid's molecules -- particle paths resembling a "drunkard's walk," which Albert Einstein had used just a few years earlier to establish the reality of atoms and molecules. Instead of impractical-to-calculate velocity, momentum, and acceleration for every molecule in the fluid, Langevin's method substituted an effective friction to damp the motion of the particle, plus a series of random jolts.

When Sivak and his colleagues used Langevin dynamics to model the behavior of molecular machines, they saw significant differences between what their exact theories predicted and what their simulations produced. They tried to come up with a physical picture of what it would take to produce these wrong answers.

"It was as if extra work were being done to push our molecules around," Sivak says. "In the real world, this would be a driven physical process, but it existed only in the simulation, so we called it 'shadow work.' It took exactly the form of a nonequilibrium driving force."

They first tested this insight with "toy" models having only a single degree of freedom, and found that when they ignored the shadow work, the calculations were systematically biased. But when they accounted for the shadow work, accurate calculations could be recovered.

"Next we looked at systems with hundreds or thousands of simple molecules," says Sivak. Using models of water molecules in a box, they simulated the state of the system over time, starting from a given thermal energy but with no "pushing" from outside. "We wanted to know how far the water simulation would be pushed by the shadow work alone."

The result confirmed that even in the absence of an explicit driving force, the finite-time-step Langevin dynamics simulation acted by itself as a driving nonequilibrium process. Systematic errors resulted from failing to separate this shadow work from the actual "protocol work" that they explicitly modeled in their simulations. For the first time, Sivak and his colleagues were able to quantify the magnitude of the deviations in various test systems.

Such simulation errors can be reduced in several ways, for example by dividing the evolution of the system into ever-finer time steps, because the shadow work is larger when the discrete time steps are larger. But doing so increases the computational expense.

The better approach is to use a correction factor that isolates the shadow work from the physically meaningful work, says Sivak. "We can apply results from our calculation in a meaningful way to characterize the error and correct for it, separating the physically realistic aspects of the simulation from the artifacts of the computer method."

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Journal Reference:

1. David A. Sivak, John D. Chodera, Gavin E. Crooks. Using nonequilibrium fluctuation theorems to understand and correct errors in equilibrium and nonequilibrium discrete Langevin dynamics simulations. Physical Review X, 2013 (in press) [link]

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Source: http://feeds.sciencedaily.com/~r/sciencedaily/matter_energy/physics/~3/Esm7pj3sTNM/130103114209.htm

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Increase Your Business Sales With Vinyl Banners Advertising | Free ...

There are different ways in which you can use banner advertisements to reach out to your target audiences. Whether it is a promotional content or simply passing across event invitation messages to audiences, vinyl banners are inexpensive and can save you the amount you have to pay to communicate to your audiences. Banner advertising entails large format printing, which is able to grab the attention of readers.

Because of their large sizes, the content can be read by many people when the banner prints are placed in strategic locations. Businesses can use these advertising tools to create brand name awareness and advertise their products and services. The business environment is very competitive and for your brand to stand out of the crowd, you have to ensure that consumers know more about the business location, what you offer, and any special promotional deals.

You could place them on top of buildings, along highways or in the streets and this attracts a large crowd to your business. Customized embroidery on the material adds value to the banner and shows uniqueness. It may be a good way of attracting more readers. People are enticed by small things and when they find something unique about a banner, they also imagine that the business or products are unique too.

In addition, these advertising tools can be used when announcing your new store, or a new location. If you plan to have a grand opening of your newly established store, you may use these banner advertisements to reach to your audiences. Overabundance of space on giant banner could allow you to create large format content that says more about the business.

Since one large banner can be viewed by many people, it means that it is a cost effective way of advertising products and services. If you have offers running in your store, you can use this advertising method to reach out to your audiences. Similarly, organizations like churches can announce their special events with the use of banner materials.

Trade shows are attended by business executives and other prominent business people and they give you a good opportunity to display your brand. In addition, institutions like churches and schools may also use print banner materials to announce special events. For college graduation ceremonies, banner prints can easily pass across the message of the special event to people within a city. They only need to be placed in strategic positions.

With primed screen printing in Vermont, you can get customized business or event vinyl banners that could help you get the recognition you want. When coupled with other advertising methods, it helps businesses grow their clientele base and increase sales. You also save on advertising costs.

For top quality vinyl banners, visit our website and choose from our selection. You can arrange for customized embroidery through links on our homepage.

Source: http://www.businesslistingnow.com/blog/increase-your-business-sales-with-vinyl-banners-advertising/

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