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These hydrogels have potential as injectable materials for medical applications, e.g., liquid injection agents that become gelatinous in the human body to keep drugs around cancerous tumors. In this study, scientists from Kansas State University, University of Nebraska, and PNNL used two native functional sequences from spider flagelliform silk protein and a trans-membrane motif of human muscle L-type calcium channel to design a self-assembling peptide, h9e.

The h9e peptide formed two novel hydrogels in Ca2+ solution and acidic pH conditions—h9e Ca2+ hydrogel and h9e acidic hydrogel. The shear-thinning, rapid-strength-recovering h9e Ca2+ hydrogel proved to have potential for drug delivery and tissue-engineering applications and was tested on mice as an injectable adjuvant for H1N1 swine influenza virus killed vaccine. The study showed it was biologically safe, improved immune response on killed H1N1 virus antigen by approximately 70%, and induced a similar H1N1-specific IgG1 antibody response compared with an oil-based commercial adjuvant.

To assess these rationally designed peptide hydrogels, the researchers used electrospray ionization followed by analysis of the resulting ions in an LTQ-Orbitrap high-resolution mass spectrometer at EMSL. The mass spectrometry experiments were conducted to identify possible precursors of the peptide assembly and nanofiber crossing, as well as the binding mode of calcium to the peptides.

Source: Medical Xpress


Switching from hydrocarbon-based transportation to systems powered by state-of-the-art fuel cells therefore seems a natural choice, but numerous obstacles have kept this technology confined to laboratories. A prime example is the problem of on-board hydrogen storage for vehicles: because ambient hydrogen gas is roughly 10,000 times less dense than gasoline, it would require impractically large tanks to obtain comparable mileage.

Compressing hydrogen gas or liquefying it at -250 °C are two ways to increase its energy content by volume. However, chemists are developing a more attractive strategy using specially designed compounds, called metal hydride clusters, to produce high hydrogen-storage densities without extreme temperatures or pressures. The metal atoms within these molecules bind to large numbers of hydrogen atoms, producing a solid that can reversibly add or remove hydrogen using mild heating or cooling.

Now, Zhaomin Hou from the RIKEN Advanced Science Institute in Wako and an international team of colleagues have isolated a new class of ‘heterometallic’ hydride clusters (Fig. 1) that may spur development of lighter and longer-lived fuel cell devices. By incorporating multinuclear rare-earth metals into their compounds, the team has produced the first high-density storage molecules that have hydrogen addition properties that can be monitored directly using x-ray diffraction—a technique that provides clear insights into cluster structure and functionality.

Rare combinations

For the past 25 years, chemists have paired so-called ‘d-block transition metals’, such as tungsten (W) and molybdenum (Mo), with lightweight rare-earth metals, such as yttrium (Y), to increase the storage capacity of hydride clusters. Because the nuclei of rare earths are shielded by many electrons, these metals can pack high numbers of hydrogen atoms into small crystal volumes without suffering electronic repulsions. Unfortunately, once hydrogen gas binds to a rare-earth metal, it tends to stay there. Mixing in d-block metals alters the rare-earth reactivity so that on-demand hydrogen storage and release can occur.

Figure 1: Heterometallic hydride clusters containing molybdenum atoms (purple spheres) and rare-earth yttrium metals (green spheres) are promising materials for on-board storage and release of hydrogen gas (light blue spheres). Credit: 2011 Zhaomin Hou

Until now, most of these combined metal hydrides were constructed using mononuclear rare-earth building blocks, such as YH, with a mononuclear d-block metal. Using a different strategy, Hou and his colleagues recently devised innovative protocols to isolate polynuclear rare-earth hydrides using large molecular ligands to trap these typically unstable compounds in place. Polynuclear hydrides feature dense, interconnected networks of ‘bridging’ hydrogen atoms connected to two or more metals—characteristics that led the researchers to explore their potential for hydrogen storage applications.

“It is not difficult to imagine that hydrogen atoms could bond to multiple metal atoms in a polynuclear polyhydride complex, and the [mode of] bonding could be different with different metal combinations,” says Hou. “However, it is not easy to prepare quality polyhydride samples for high-precision structure determinations. Hydride complexes containing both rare-earth and d-block transition metals are even more difficult to prepare because of their air- and moisture-sensitivity.”

A five-way first

Figure 2: Monitoring the reversible addition and release of a hydrogen gas molecule to a molybdenum-yttrium cluster in real time with x-ray crystallography has revealed the first atom-resolved insights into hydrogen storage by organometallic crystals. Credit: 2011 Zhaomin Hou

Performing their experiments inside nitrogen-filled and humidity-free enclosures, the team mixed one of their carefully prepared polynuclear complexes—four yttrium metals and eight hydrogen atoms held together by bulky organic ligands—with either a Mo or W pentahydride. After precipitating crystals out of the reaction, they used x-ray and neutron diffraction experiments to view their product’s atomic structure. These measurements showed that the two metallic components fused together, yielding a Y4MH11 (M = Mo, W) hydride with double-, triple-, and quadruple-bridged hydrogen atoms.

Zapping the penta-metallic polyhydride with ultraviolet light enabled the team to remove a protective phosphorus ligand and increase the hydrogen bridging density within the cluster. This produced the first hydride cluster where hydrogen is bonded to five metals in a distinctive symmetry known as trigonal bipyramidal. “The confirmation of a penta-coordinated hydrogen atom in this geometry is unprecedented,” says Hou.

Step-by-step scrutiny

Hou and colleagues’ experiments then demonstrated that their heterometallic clusters possessed critical hydrogen storage and release capabilities. Heating H2 and Y4WH11 to 80 °C caused an oxidative addition of the gas molecule to the cluster, which they could reverse through ultraviolet-light treatment. Despite the Y4MoH11 molecule not responding to the same chemical tricks, the researchers discovered that applying a vacuum could suck H2 from the cluster, giving a new Y4MoH9 complex. Exposing this compound to hydrogen gas at room temperature spontaneously regenerated the original molecule (Fig. 2).

According to Hou, the most striking aspect of this chemistry is that the hydrogen addition to the Y4MoH9 cluster can be followed from single crystal to single crystal—meaning that the starting material, the reaction intermediates, and the product all retain the same rigid morphology. “No metal hydrides have previously shown such excellent crystallinity,” he notes.

After gingerly sealing a Y4MoH9 crystal into a thin, hydrogen-filled capillary tube, the researchers monitored the spontaneous addition reaction over 60 hours. As the cluster gradually took in hydrogen and changed color from black to red, they watched—at precision greater than one-millionth of a meter—yttrium and molybdenum atoms separate and shift within the crystal unit cell. By providing the first-ever atom-resolved views of active sites and bonding modes for hydrogen addition to an organometallic crystal, these findings should aid design of more sophisticated alloys in the future.

Theoretical calculations performed by the researchers indicated that combining two metals with starkly different electronic properties played a big role in giving the clusters their unique reactivity. With wide swaths of the periodic table available for exploring using this technique, breakthroughs in heterometallic hydride materials may have only just begun.

Source: RIKEN


The incorporation of such single-molecule elements could enable smaller, faster, and more energy-efficient electronics.

The research findings, supported by a $1 million grant from the W.M. Keck Foundation, were published online in the Nov. 14 issue of Nano Letters.

"This new switch is superior to existing single-molecule concepts," said Hrvoje Petek, principal investigator and professor of physics and chemistry in the Kenneth P. Dietrich School of Arts and Sciences and codirector of the Petersen Institute for NanoScience and Engineering (PINSE) at Pitt. "We are learning how to reduce electronic circuit elements to single molecules for a new generation of enhanced and more sustainable technologies."

The switch was discovered by experimenting with the rotation of a triangular cluster of three metal atoms held together by a nitrogen atom, which is enclosed entirely within a cage made up entirely of carbon atoms. Petek and his team found that the metal clusters encapsulated within a hollow carbon cage could rotate between several structures under the stimulation of electrons. This rotation changes the molecule's ability to conduct an electric current, thereby switching among multiple logic states without changing the spherical shape of the carbon cage. Petek says this concept also protects the molecule so it can function without influence from outside chemicals.

Because of their constant spherical shape, the prototype molecular switches can be integrated as atom-like building blocks the size of one nanometer (100,000 times smaller than the diameter of a human hair) into massively parallel computing architectures.

The prototype was demonstrated using an Sc3N@C80 molecule sandwiched between two electrodes consisting of an atomically flat copper oxide substrate and an atomically sharp tungsten tip. By applying a voltage pulse, the equilateral triangle-shaped Sc3N could be rotated predictably among six logic states.

The research was led by Petek in collaboration with chemists at the Leibnitz Institute for Solid State Research in Dresden, Germany, and theoreticians at the University of Science and Technology of China in Hefei, People's Republic of China. The experiments were performed by postdoctoral researcher Tian Huang and research assistant professor Min Feng, both in Pitt's Department of Physics and Astronomy.

Source: ScienceDaily


The structures have potential applications in drug delivery to treat diseases and imaging for cancer research. Two types of nanotubes are created in the manufacturing process, metallic and semiconducting. Until now, however, there has been no technique to see both types in living cells and the bloodstream, said Ji-Xin Cheng, an associate professor of biomedical engineering and chemistry at Purdue University.

The imaging technique, called transient absorption, uses a pulsing near-infrared laser to deposit energy into the nanotubes, which then are probed by a second near-infrared laser.

The researchers have overcome key obstacles in using the imaging technology, detecting and monitoring the nanotubes in live cells and laboratory mice, Cheng said.

"Because we can do this at high speed, we can see what's happening in real time as the nanotubes are circulating in the bloodstream," he said.

Findings are detailed in a research paper posted online Sunday (Dec. 4) in the journal Nature Nanotechnology.

The imaging technique is "label free," meaning it does not require that the nanotubes be marked with dyes, making it potentially practical for research and medicine, Cheng said.

"It's a fundamental tool for research that will provide information for the scientific community to learn how to perfect the use of nanotubes for biomedical and clinical applications," he said.

The conventional imaging method uses luminescence, which is limited because it detects the semiconducting nanotubes but not the metallic ones.

The nanotubes have a diameter of about 1 nanometer, or roughly the length of 10 hydrogen atoms strung together, making them far too small to be seen with a conventional light microscope. One challenge in using the transient absorption imaging system for living cells was to eliminate the interference caused by the background glow of red blood cells, which is brighter than the nanotubes.

The researchers solved this problem by separating the signals from red blood cells and nanotubes in two separate "channels." Light from the red blood cells is slightly delayed compared to light emitted by the nanotubes. The two types of signals are "phase separated" by restricting them to different channels based on this delay.

Researchers used the technique to see nanotubes circulating in the blood vessels of mice earlobes.

"This is important for drug delivery because you want to know how long nanotubes remain in blood vessels after they are injected," Cheng said. "So you need to visualize them in real time circulating in the bloodstream."

The structures, called single-wall carbon nanotubes, are formed by rolling up a one-atom-thick layer of graphite called graphene. The nanotubes are inherently hydrophobic, so some of the nanotubes used in the study were coated with DNA to make them water-soluble, which is required for them to be transported in the bloodstream and into cells.

The researchers also have taken images of nanotubes in the liver and other organs to study their distribution in mice, and they are using the imaging technique to study other nanomaterials such as graphene.

More information: Label-Free Imaging of Semiconducting and Metallic Carbon Nanotubes in Cells and Mice Using Transient Absorption Microscopy, Nature Nanotechnology.

Source: PhysOrg


This would include what is referred to as the "exome," But as University of North Carolina at Chapel Hill medical geneticists point out, this avalanche of information also includes the totality of one's genetic mutations and as such arrives with both promise and threats associated with its use.

James P. Evans, MD, PhD is the Bryson Distinguished Professor of Genetics and Medicine at UNC and is a member of the Lineberger Comprehensive Cancer Center. He is also editor-in-chief of Genetics in Medicine, the journal of the American College of Medical Genetics. "What you're now dealing with is a real medical test, one that has the power to help, hurt and to confuse. I believe we need to think carefully about how to best use it and how that use should be regulated in order to maximize benefit and minimize harm," he said.

In a commentary published in JAMA on Wednesday, Dec. 7, 2011, Evans and UNC co-author Jonathan S. Berg, MD, PhD, Lineberger member and assistant professor of genetics and medicine, argue that whole genome and whole exome sequencing technology "will routinely uncover both trivial and important medical results, both welcome and unwelcome … and presents the medical community with new challenges."

"What we have had up until this point with direct-to-consumer genetic testing, despite all the hoopla, was arguably rather trivial from the standpoint of either benefits or threats. It was a fairly worthless technology because it really didn't give people medically significant findings," Evans said.

"Now we are entering an entirely different era due to the advent of robust sequencing technology. We have now the potential to tell people very real and important things about their genomes. Some of those things can be very useful and very welcome if acted upon in the right way, but some of that information may not be very welcome to people: being at high risk for an untreatable disease such as dementia, for example."

As to regulation, Evans and Berg suggest that it need not be draconian but must be nuanced. "Basically, what we call for is that this new generation of medical testing be treated like other medical tests that involve complex medical information – and that there should be a reasonable expectation that an individual who gets it done has some relationship with a qualified care provider."

That person doesn't need to be a physician, Evans adds. "There are genetic counselors capable of dealing with this. But it must be a person not employed by the company or laboratory doing the testing since that invites egregious conflict of interest."

As physicians pledged to avoid causing harm, the authors acknowledge the inevitable tension that exists between paternalism and the reasonable protection of people. They point to three compelling arbiters of whether the acquisition of medical information should require a relationship with a healthcare professional: the information's complexity, ability to mislead and potential for harm.

"The advent of next generation sequencing technology marks a threshold at which genomic testing easily meets these bars," they state.your complete set of protein-coding sequences.

Source: Medical Xpress


The Vienna University of Technology is the only research facility in the world, where single atoms can be controllably coupled to the light in ultra-thin fiber glass. Specially prepared light waves interact with very small numbers of atoms, which makes it possible to build detectors that are extremely sensitive to tiny trace amounts of a substance.

Professor Arno Rauschenbeutel’s team, one of six research groups at the Vienna Center for Quantum Science and Technology, has presented this new method in the journal Physical Review Letters. The research project was carried out in collaboration with the Johannes Gutenberg University in Mainz, Germany.

The light wave in the glass fiber sticks out and touches the atoms trapped above and below the glass fiber.

Ultra-Thin Glass Fibers

The glass fibers used for the experiment are only five hundred millionths of a millimeter thick (500 nm). In fact, they are even thinner than the wavelength of visible light. “Actually, the light wave does not really fit into the glass fiber, it sticks out a little”, Arno Rauschenbeutel explains. And this is precisely the big advantage of the new method: the light wave touches atoms which are located outside of, but very close to, the glass fiber. “First, we trap the atoms, so that they are aligned above and below the glass fiber, like pearls on a string”, says Rauschenbeutel. The light wave sent through the glass fiber is then modified by each individual atom it passes. By measuring changes in the light waves very accurately, the number of atoms trapped near the fiber can be determined.

Atoms Change the Speed of Light

When scientists study the interaction of atoms and light, they usually look at rather disruptive effects – at least on a microscopic scale: Atoms can, for example, absorb photons and emit them later in a different direction. This way, atoms can be accelerated and hurled away from their original position. In the glass fiber experiments at Vienna UT however, a very soft interaction between light and atoms is sufficient: “The atoms close to the glass fiber decelerate the light very slightly”, Arno Rauschenbeutel explains. When the light wave oscillates precisely upwards and downwards in the direction of the atoms, the wave is shifted by a tiny amount. Another light wave oscillating in a different direction does not hit any atoms and is therefore hardly decelerated at all. Light waves of different polarization directions are sent through the glass fiber – and their relative shift due to their different speed is measured. This shift tells the scientists how many atoms have delayed the light wave.

Detecting Single Atoms

Hundreds or thousands of atoms can be trapped, less than a thousandth of a millimeter away from the glass fiber. Their number can be determined with an accuracy of several atoms. “In principle, our method is so precise that it can detect as few as ten or twenty atoms”, says Arno Rauschenbeutel. “We are working on a few more technical tricks – such as the reduction of the distance between the atoms and the glass fiber. If we can do this, we should even be able to reliably detect single atoms.”

Non-Destructive Quantum Measurements

The new glass fiber measuring method is not only important for new detectors, but also for basic quantum physical research. “Usually the quantum physical state of a system is destroyed when we measure it”, Rauschenbeutel explains. “Our glass fibers make it possible to control quantum states without destroying them.” The atoms close to the glass fiber can also be used to tune the plane in which the light wave oscillates. Nobody can tell yet, which new technological possibilities may be opened up by that. “Quantum optics is an incredibly innovative research area today – and the Vienna research groups in this field are competing among the best in the world”, says Arno Rauschenbeutel.

Source: Vienna University of Technology


Broken promises are nothing new in Washington, DC. Yet even by the Beltway’s jaded standards, President Obama’s role reversal from one time medicinal cannabis sympathizer to White House weed-whacker is remarkable.

Indeed, the man who once pledged on the campaign trail that he was “not going to be using Justice Department resources to try to circumvent state laws on this issue,” has – since taking the Presidential oaths of office – done virtually everything in his administration’s power to do precisely that. Yet he's taken these steps at the very time that a record number of Americans, including 57 percent of democrats and a whopping 69 percent of self-described liberals, endorse doing just the opposite. Nonetheless, in recent months, the Obama administration – via a virtual alphabet soup of federal agencies – has launched an unprecedented series of attacks against medical cannabis patients, providers, and in some cases even their advocates.

 To review:

-- Deputy Attorney General James Cole, along with the four US Attorneys from California, has ramped up federal efforts to close or displace several hundreds of medical cannabis providers in California. Their tactics have included: raiding specific dispensaries and prosecuting their owners; filing civil forfeiture proceedings against landlords who rent their property to medical marijuana providers; threatening to federally prosecute newspapers and radio stations who accept ad revenue from medical cannabis operations; and, most recently, intimidating local lawmakers who have either enacted or are publicly supportive of cannabis oversight regulations. Speaking with radio station KQED San Francisco last month, Tommy LaNier – Director of the White House Office of National Drug Control Policy's National Marijuana Initiative – boasted about the administration’s efforts to strong-arm local officials, stating "[We] have ... advised those places where they're trying to regulate marijuana -- which is illegal under the Control Substances Act -- (that) they cannot do that.”

-- In Colorado, United States Attorney John Walsh has sent letters to owners of dozens of the Centennial State’s medical cannabis facilities stating, "Action will be taken to seize and forfeit their property" if they do not cease their operations. Unlike similarly targeted dispensaries in California, the operations on Walsh’s hit list are explicitly licensed by the state and thus fully compliant with state law – a fact that Walsh’s letters readily acknowledge but appear content to ignore. "This ... constitutes formal notice that action will be taken to seize and forfeit (your) property if you do not cause the sale and/or distribution of marijuana and marijuana-infused substances at (this) location to be discontinued,” they state. “[T]he Department of Justice has the authority to enforce federal law even when such activities may be permitted under state law.” Ironically, the Justice Department’s letters arrived just weeks after US Attorney General Eric Holder publicly told (read: lied to) Colorado Congressman Jared Polis, an ardent supporter of the medicinal cannabis industry, that that the federal government would only target medical cannabis operators that "use marijuana in a way that's not consistent with the state statute."

-- But the Obama Justice Department isn’t only sending letters to cannabis dispensaries owners and their landlords. Last year, the DOJ also mailed letters to numerous state lawmakers, including the Governors of Delaware, Rhode Island, Vermont, and Washington, as they were debating legislation to allow for the licensed distribution of medical cannabis. The letters threatened federal prosecution for those involved with said efforts – including, in some cases, state civil servants – if the measures went forward. As a result, most didn’t.

The Justice Department isn’t the only agency directly involved in the administration’s medical pot crackdown. Also over the past six months:

-- The IRS has assessed crippling penalties on tax-paying medical cannabis facilities in California by denying these operations from filing standard expense deductions;

-- The Department of Treasury has strong-armed local banks and other financial institutions into closing their accounts with medicinal marijuana operators. In Colorado, where the state’s estimated 700 licensed cannabis dispensaries are routinely subjected to state audits, there no longer remains even a single bank willing to openly do business with med-pot operators.

-- The Bureau of Alcohol Tobacco and Firearms has sternly warned firearms dealers not to sell guns to medical cannabis consumers, and stated that patients who otherwise legally possess firearms are in violation of federal law and may face criminal prosecution;

-- In July, the Drug Enforcement Administration rejected a nine-year-old administrative petition that called for hearings regarding the federal rescheduling of marijuana for medical use, ignoring extensive scientific evidence of its medical efficacy. “[T]here are no adequate and well-controlled studies proving (marijuana's) efficacy; the drug is not accepted by qualified experts,” the agency alleged. “At this time, the known risks of marijuana use have not been shown to be outweighed by specific benefits in well-controlled clinical trials that scientifically evaluate safety and efficacy.”

-- This fall, the National Institute on Drug Abuse rejected an FDA-approved protocol to allow for clinical research assessing the use of cannabis to treat post-traumatic stress disorder; a spokesperson for the agency conceded, “We generally do not fund research focused on the potential beneficial medical effects of marijuana.”

-- The DEA has reduced the total number of federally qualified investigators licensed to study plant marijuana in humans to 14 nationwide.

Most recently, and perhaps most egregiously, the DEA acknowledged that it was investigating a Montana state lawmaker for potentially conspiring to violate federal anti-marijuana laws. The lawmaker, Rep. Diane Sands – a Democrat from Missoula, Montana – served as the chairwoman of a 2011 interim legislative committee that sought to enact statewide regulations governing the production and distribution of medical pot, which has been legal in the state since 2004. "Can you say McCarthy?” she told The Missoulian newspaper.  “This sounds like stuff from the House Un-American Activities Committee and Joe McCarthy. So once you talk about medical marijuana in reasonable terms, you're on some sort of list of possible conspirators. … It's ridiculous, of course, but it's also threatening to think that the federal government is willing to use its influence and try to chill discussion about this subject."

* * *

So has the Obama administration collectively lost its mind when it comes to the subject of medical cannabis? That certainly seems to be the case. But the bigger question still remains: Why now?

Speculation among reformers and the general public is widespread. Many activists contend that the administration's about face is due to pressure from the pharmaceutical industry, which they surmise may be hoping to eliminate competition in the marketplace for their own forthcoming, soon-to-be FDA-approved cannabis-based drug. Others believe that Obama’s crackdown is a Machiavellian attempt on the part of the President and his advisors to appeal to independent, conservative-leaning swing voters during an election year. Still others argue that the recent attacks have little to do with President Obama at all. Instead, they believe the efforts of the DEA, DOJ, and other federal agencies are being coordinated primarily by drug war hawks within the administration, many of which are holdovers from the George W. Bush regime, such as DEA administrator Michele Leonhart. Adding weight to this claim are recent statements from US Attorney Andre Birotte, who acknowledged that the DOJ’s recent activities were led by the federal prosecutors themselves and were not instigated by either President Obama or Attorney General Eric Holder – both of which are engaged in their own personal battles for political survival and, as a result, are unlikely to expend even a shred of political capital to halt the efforts of the administration’s more ardent drug warriors.

There may be a grain of truth in all of the above theories. But perhaps the greatest underlying motivator for the administration’s sudden and severe crackdown on medical marijuana providers and patients is its desire to preserve America’s longstanding criminalization of cannabis for everyone else. There is little doubt that the rapid rise of the medical marijuana industry and the legal commerce inherent to it is arguably the single biggest threat to federal cannabis prohibition. Just look at the poll numbers. According to Gallup, in 1996 – when California became the first state to allow for the legally sanctioned use of cannabis therapy – only 25 percent of Americans backed legalizing marijuana for all adults. (Seventy-three percent of respondents at that time said they opposed the idea.) Fast forward to 2011. Today, a record high 50 percent of Americans support legalizing the plant outright and only 46 percent of respondents oppose doing so. It’s this rapid rise in the public’s support for overall legalization that no doubt has the Obama administration, and the majority of America’s elected officials, running scared.

While the passage and enactment of statewide medical marijuana laws – 16 states and the District of Columbia now have laws recognizing marijuana’s therapeutic use on the books – is not solely driving the public’s shift in support for broader legalization, it is arguably a major factor. Why? The answer is simple. Tens of millions of Americans residing in these states are learning, first hand, that they can coexist with marijuana being legal! And that is the lesson the federal government fears most.

In states like California and Colorado, voters have largely become accustomed to the reality that there can be safe, secure, well-run businesses that deliver consistent, reliable, tested cannabis products. They have come to understand that well-regulated cannabis dispensaries can revitalize sagging economies, provide jobs, and contribute taxes to budget-starved localities. Most importantly, the public in these states and others are finally realizing that all the years of scaremongering by the government about what would happen if marijuana were legal, even for sick people, was nothing but hysterical propaganda. As a result, a majority of American voters are now for the first time asking their federal officials: ‘Why we don’t just legalize marijuana for everyone in a similarly responsible manner?’

That is a question the President remains unable and unwilling to answer. And the administration appears willing to go to any lengths to avoid it.

Source: - Editor's Note: This article incorrectly said Rep. Diane Sands is from Billings, Montana. She represents Missoula, Montana.

Paul Armentano is the deputy director of NORML (the National Organization for the Reform of Marijuana Laws), and is the co-author of the book Marijuana Is Safer: So Why Are We Driving People to Drink (2009, Chelsea Green).

By Admin (from 18/02/2012 @ 08:05:58, in en - Science and Society, read 1395 times)

Fifty years after the pioneering discovery that a protein's three-dimensional structure is determined solely by the sequence of its amino acids, an international team of researchers has taken a major step toward fulfilling the tantalizing promise: predicting the structure of a protein from its DNA alone.

The team at Harvard Medical School (HMS), Politecnico di Torino / Human Genetics Foundation Torino (HuGeF) and Memorial Sloan-Kettering Cancer Center in New York (MSKCC) has reported substantial progress toward solving a classical problem of molecular biology: the computational protein folding problem.

The results was published on Dec. 7, 2011 in the journal PLoS ONE.

In molecular biology and biomedical engineering, knowing the shape of protein molecules is key to understanding how they perform the work of life, the mechanisms of disease and drug design. Normally the shape of protein molecules is determined by expensive and complicated experiments, and for most proteins these experiments have not yet been done. Computing the shape from genetic information alone is possible in principle. But despite limited success for some smaller proteins, this challenge has remained essentially unsolved. The difficulty lies in the enormous complexity of the search space, an astronomically large number of possible shapes. Without any shortcuts, it would take a supercomputer many years to explore all possible shapes of even a small protein.

Studying related proteins, researchers identified pairs of amino acid residues (left) that seemed to change in lockstep in the evolutionary record. These co-varying pairs indicated points on protein (middle) likely to be in contact after folding, giving researchers enough clues to create a computational model of the protein's three-dimensional structure (right). Credit: Terry Helms/Memorial Sloan-Kettering Cancer Center.

"Experimental structure determination has a hard time keeping up with the explosion in genetic sequence information," said Debora Marks, a mathematical biologist in the Department of Systems Biology at HMS, who worked closely with Lucy Colwell, a mathematician, who recently moved from Harvard to Cambridge University. They collaborated with physicists Riccardo Zecchina and Andrea Pagnani in Torino in a team effort initiated by Marks and computational biologist Chris Sander of the Computational Biology Program at MSKCC, who had earlier attempted a similar solution to the problem, when substantially fewer sequences were available.

"Collaboration was key," Sander said. "As with many important discoveries in science, no one could provide the answer in isolation."

The international team tested a bold premise: That evolution can provide a roadmap to how the protein folds. Their approach combined three key elements: evolutionary information accumulated for many millions of years; data from high-throughput genetic sequencing; and a key method from statistical physics, co-developed in the Torino group with Martin Weigt, who recently moved to the University of Paris.

Using the accumulated evolutionary information in the form of the sequences of thousands of proteins, grouped in protein families that are likely to have similar shapes, the team found a way to solve the problem: an algorithm to infer which parts of a protein interact to determine its shape. They used a principle from statistical physics called "maximum entropy" in a method that extracts information about microscopic interactions from measurement of system properties.

"The protein folding problem has been a huge combinatorial challenge for decades," said Zecchina, "but our statistical methods turned out to be surprisingly effective in extracting essential information from the evolutionary record."

With these internal protein interactions in hand, widely used molecular simulation software developed by Axel Brunger at Stanford University generated the atomic details of the protein shape. The team was for the first time able to compute remarkably accurate shapes from sequence information alone for a test set of 15 diverse proteins, with no protein size limit in sight, with unprecedented accuracy.

"Alone, none of the individual pieces are completely novel, but apparently nobody had put all of them together to predict 3D protein structure," Colwell said.

To test their method, the researchers initially focused on the Ras family of signaling proteins, which has been extensively studied because of its known link to cancer. The structure of several Ras-type proteins has already been solved experimentally, but the proteins in the family are larger--with about 160 amino acid residues--than any proteins modeled computationally from sequence alone.

"When we saw the first computationally folded Ras protein, we nearly went through the roof," Marks said. To the researchers' amazement, their model folded within about 3.5 angstroms of the known structure with all the structural elements in the right place. And there is no reason, the authors say, that the method couldn't work with even larger proteins.

The researchers caution that there are other limits, however: Experimental structures, when available, generally are more accurate in atomic detail. And, the method works only when researchers have genetic data for large protein families. But advances in DNA sequencing have yielded a torrent of such data that is forecast to continue growing exponentially in the foreseeable future.

The next step, the researchers say, is to predict the structures of unsolved proteins currently being investigated by structural biologists, before exploring the large uncharted territory of currently unknown protein structures.

"Synergy between computational prediction and experimental determination of structures is likely to yield increasingly valuable insight into the large universe of protein shapes that crucially determine their function and evolutionary dynamics," Sander said.

More information: "Protein 3D structure computed from evolutionary sequence variation," Marks et al. PLoS ONE, December 6, 2011

Source: Harvard Medical School

By Admin (from 22/02/2012 @ 11:02:47, in en - Science and Society, read 1702 times)

Injuries involving torn or degraded joint cartilage can be very debilitating, especially since that cartilage is incapable of healing itself, past a certain point. It's not surprising, therefore, that numerous scientists have been working on ways of either growing replacement cartilage outside of the body, or helping the body to regrow it internally. Just a few of the efforts have included things like stem cell-seeded bandages, bioactive gel, tissue scaffolds, and nanoscale stem cell-carrying balls. Now, researchers from Cleveland's Case Western Reserve University have announced something else that shows promise - sheets of mesenchymal (bone and cartilage-forming) stem cells, permeated with tiny beads filled with the growth factor beta-1.

The "traditional" approach to growing cartilage from a sheet of stem cells would involve soaking that sheet in a solution of the growth factor. Over time, that solution would cause the stem cells to differentiate into cartilage cells.

The Case Western team, however, chose to encapsulate the beta-1 in biodegradable gelatin microspheres, which were then distributed throughout the structure of the sheets. There are several advantages to introducing the growth factor in this way.

For starters, once the spheres degrade, they leave empty spaces between the cells. This creates a strong, scaffold-like structure, and allows the new cartilage to better retain water - the better that it can retain water, the more resilient it is to damage.

Also, the microspheres degrade at a controlled rate, when exposed to enzymes released by the stem cells. This means that cells throughout the sheet, inside and out, come into contact with the growth factor at about the same time, and thus the sheet forms into cartilage more uniformly.

Additionally, it is possible to tweak the microspheres' rate of degradation, by varying the amount of cross-linking in their molecular structure. To that end, the scientists tested separate sheets containing sparsely cross-linked and highly cross-linked beta-1-laden spheres. They also tried out sheets containing sparsely cross-linked spheres containing no beta-1, but that were soaked in a solution of it, instead.

All three types of sheets transformed into cartilage that was thicker and more resilient than that obtained from a solution-soaked control sheet containing no microspheres. The thickest cartilage, however, came from the sheet with the sparsely cross-linked beta-1-containing spheres. This was because the spheres degraded quicker than their highly cross-linked counterparts, providing the stem cells with a longer, more continuous exposure to the growth factor.

The tissue created was similar to the articular cartilage found in the knee, although it wasn't as mechanically strong as the real thing. The Case Western scientists are now working on ways of toughening it up, so that it could one day find use in human patients. They believe that within just one or two weeks of being cultured, the sheets could be implanted in the body, where the mechanical forces of the joints would help build and strengthen the new cartilage.

Source: GIZMAG


A team of researchers from led by Guillaume Gervais from McGill’s Physics Department and Mike Lilly from Sandia National Laboratories, have managed to develop one of the smallest electronic circuits in the world using nanowires spaced across each other by a distance so small, it has to be measured at an atomic level.

Miniaturization has been the dominant trend in the digital industry for years, and nano-electronics, with which scientists have been fiddling for the past 20 years, is considered as the next obvious step, allowing for even smaller and powerful electronic devices.

“People have been working on nanowires for 20 years,” says Sandia lead researcher Mike Lilly. “At first, you study such wires individually or all together, but eventually you want a systematic way of studying the integration of nanowires into nanocircuitry. That’s what’s happening now. It’s important to know how nanowires interact with each other rather than with regular wires.”

While nanowires have been studied extensively in the past, this current study is the first of its kind to approach how the wires in an electronic circuit interact with one another when packed so tightly together. The researchers used gallium-arsenide nanowire structures which they placed one above the other, separated by only a few atomic layers of extremely pure, home-grown crystal – two wires separated by only about 150 atoms or 15 nanometers (nm).

At this extremely tiny scale, new properties and characterisctics arise, along with inherent issues in the path of the researcher’s study. For one, the nano-wires have been envisoned as a 1-D structure, very different from your usual, bulk 3-D wire common in any kind of electrical device. Through these types of wires, current can only flow in one direction, not horizontally, vertically, back/forward like in a typical 3-D capable.

“In the long run, our test device will allow us to probe how 1-D conductors are different from 2-D and 3-D conductors,” Lilly said. “They are expected to be very different, but there are relatively few experimental techniques that have been used to study the 1-D ground state.”

At the nanoscale, also, the behavior of the circuit is described by quantum physics. In our case, by the introduction of Coulomb’s drag effect. This force operates between wires, and is inversely proportional to the square of the clearance. This is why in conventional circuitry, where the gap between wires is quite visible, this drag force can be considered negligible, however at nanodistances, the force becomes large enough for it to disturb electrons. This causes the current flowing through to the nanowires to march in opposite directions.

This means that a current in one wire can produce a current in the other one that is either in the same or the opposite direction.

“The amount is very small,” said Lilly, “and we can’t measure it. What we can measure is the voltage of the other wire.”

Coulomb’s drag effect is still not very well understood at this time, however what is know is that “enough electrons get knocked along that they provide positive source at one wire end, negative at the other,” Lilly said.

Yes, nanowires will allow for a even smaller scale of the digital world, however this is just the most visible benefit, out of many which are set to revolutionize electronics in the following decades.

One of the biggest hassles scientists working in the field of electronics at this time is how to control dissipated heat, the energy lost to the environment. This is a great concern to computer designers especially since millions of integrated circuits are currently employed in most devices today, and the heat generated by them has to be controlled. Well-known theorist Markus Büttiker speculates that it may be possible to harness the energy lost as heat in one wire by using other wires nearby. Basically, as the distance is smaller, the heat generated will be smaller as adjacent wires can easily absorb those minute quantities.

Also, speed will be a parameter which will be improved, as smaller distances translate in shorter time for signals to travel from one point to another. In this present research, the Sandia National Laboratories experiment rendered an unexpected voltage increases of up to 25 percent.

Source: ZME Science

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