Wednesday, September 22, 2010


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In a world where doctors can treat the most devastating illnesses, the common cold remains elusive.

That's because up until recently, scientists knew little about the viruses that spread this seasonal nuisance.

But that may be changing now that researchers have mapped one virus's atomic structure using the Advanced Photon Source (APS) at the U.S. Department of Energy's Argonne National Laboratory.

Glen Nemerow and Vijay Reddy have been studying the human adenovirus—responsible for 10 percent of colds in addition to other, more harmful infections—for more than a dozen years.

Nemerow, a professor in the Department of Immunology and Microbial Science at The Scripps Research Institute in La Jolla, Calif., and Reddy, an associate professor in Scripp's Department of Molecular Biology, paired up in the late 1990s.

Together they mapped the virus using X-ray crystallography, a technique in which X-rays are beamed at a virus crystal, resulting in a diffraction pattern that helps scientists understand the virus' shape.

Their findings were published in the journal Science on August 27, 2010.

"The more we know about the virus' structural features, the better we understand how it functions," Nemerow said. "This will help us learn more about how the virus infects host cells so that we can develop effective anti-virals."

The major protein component of adenovirus, called hexon, was crystallized—meaning that the proteins were arranged in a way that they could be studied by X-ray diffraction—in 1968. But it wasn't until 2000 that the refined structure of the hexon could be determined.

By contrast, Nemerow and Reddy determined the structure of the entire virus. This has allowed them to learn how that major protein or hexon was incorporated into the virus and how it interacts with other proteins.

The Scripps scientists said their discovery would not be possible without the use of Argonne's APS.

"The use of this particular beam line was critical," Reddy said. "You need to have a high resolution to be able to visualize the virus in greater detail. We could only obtain that at Argonne."

Reddy said he and Nemerow tried a number of other beam lines before they settled on what is known as the General Medicine and Cancer Institutes Collaborative Access Team (GM/CA-CAT) at the APS.

"The beam line is quite intense compared to others," Reddy said. "It's more laser-like."

Reddy said he and Nemerow value not only the strength of the X-ray but the diligence with which the line is improved and maintained.

"The features of the beam line are absolutely essential," Nemerow said. "We need a very high energy X-ray beam focused on a very small area to provide the highest resolution data."

But even before they could get to the APS, the two had to solve nearly insurmountable obstacles.

"Perhaps the most critical step in this process is growing the crystals of the virus," Reddy said. "That is very important. Not all crystals are able to diffract to a high resolution, and that is a tremendous obstacle in structural biology. It took us five years to cultivate the crystals we needed."

The pair started coming to Argonne in 2005 and stayed for several days at a time to collect their data.

Robert Fischetti, a senior scientist in the biosciences division at Argonne who has worked with Nemerow and Reddy for years, said that GM/CA-CAT is constantly making improvements to the beam line.

"We spent years perfecting the uniformity of the beam just as they perfected the crystals," he said.

(Photo: ANL)



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Earth today is one of the most active planets in the Solar System, and was probably even more so during the early stages of its life. Thanks to the plate tectonics that continue to shape our planet’s surface, remnants of crust from Earth’s formative years are rare, but not impossible to find. A paper published in Nature Sept. 2 examines how some ancient rocks have resisted being recycled into Earth’s convecting interior.

Throughout the world there exist regions of ancient crust, referred to as cratons, which have resisted being recycled into the interior of our tectonically dynamic planet. These geologic anomalies appear to have withstood major deformation thanks to the presence of mantle roots. A mantle root is a portion of Earth’s mantle that lies beneath the craton, extending like the root of a tooth into the rest of the underlying mantle.

Just like a tooth, the mantle root of a craton is compositionally different from the normal mantle into which it protrudes. It is also colder, causing it to be more rigid. These roots were formed in ancient melting events and are intrinsically more buoyant than the surrounding mantle. The melting removed much of the calcium, aluminum, and iron that would normally form dense minerals. Thus, these roots act as rafts bobbing on a vigorously convecting mantle, on which old fragments of continental crust may bask in comparative safety.

However, geophysical calculations have suggested that this buoyancy is not enough to stop destruction of the mantle roots. According to these calculations, the hotter temperatures that are widely thought to have existed in Earth’s mantle about 2.5 to 3 billion years ago should have warmed and softened up the base of these roots sufficiently to allow them to be gradually eroded from below, leading to their eventual destruction as they were entrained, piece by piece, into the convecting mantle. A stronger viscosity contrast between the root and the underlying mantle is required to ensure preservation.

In the Sept. 2 issue of Nature, Anne Peslier, an ESCG-Jacobs Technology scientist working at NASA-Johnson Space Center and her colleagues David Bell from Arizona State University and Alan Woodland and Marina Lazarov from the University of Frankfurt, published measurements of the trace water content of rocks from the deepest part of a mantle root that offer an explanation for this mystery.

“It has long been suspected, but not proven, that cratonic mantle roots are dryer than convecting upper mantle,” explains Bell, an associate research scientist in the School of Earth and Space Exploration and the department of chemistry and biochemistry in ASU’s College of Liberal Arts and Sciences. “The presence of very small quantities of water is known to weaken rocks and minerals. During partial melting, such as that experienced by the mantle roots, water – like calcium, aluminum and iron – is also removed.”

The researchers used samples found in diamond mines of Southern Africa, where the ancient crust of the Kaapvaal craton was pierced about 100 million years ago by gas-charged magmas called kimberlites. These magmas were generated at depths of about 125 miles (200 kilometers) beneath the mantle root and ascended rapidly (in a matter of hours) through the Earth via deep fractures, bringing with them pieces of the rocks traversed, including diamonds. After erupting explosively at the surface, the magmas solidified into the pipe-like bodies of kimberlite rock that were subsequently mined for their diamonds.

The mantle rocks analyzed by the team were transported from a range of depths down to 125 miles (200 km) below the surface, where they had resided since their formation around 3 billion years ago. The samples of rock called peridotite are composed mainly of the mineral olivine, with minor quantities of pyroxenes and garnet. Olivine is, because if its abundance, the mineral believed to control the rheological properties of peridotite.

What Peslier and colleagues found is that beyond a depth of about 112 miles (180 km), the water content of olivines begins to decline with depth, so that the olivine in peridotite samples from the very base of the cratonic mantle root contained hardly any water. That makes these olivines very hard to deform or break up, and may generate the strong viscosity contrast with that geophysical models of craton root stability require.

Why the bottom of the mantle root has dry olivines is still a matter of speculation. One possibility, suggested by Woodland, is that reducing conditions thought to prevail at these depths would ensure that fluids would be rich in methane instead of water. Bell suggests that melts generated in the asthenosphere, such as those eventually giving rise to kimberlite eruptions, may scavenge any water present while passing through the base of the cratonic root and transport it into the overlying shallower mantle.
These results reiterate the belief shared by many scientists that knowing how much water is present deep in terrestrial planets and moons, like Earth, Mars or the Moon, is important to understanding their dynamics and evolutionary history.

(Photo: David R. Bell / ASU)

Arizona State University


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Claims that a tomb at Vergina, Greece, the ancient burial place of the Macedonian royal family in the fourth century BC, contains the body of King Philip III Arrhidaios, half-brother of Alexander the Great, and not Philip II, Alexander’s father, are called into question by researchers from the Universities of Bristol, Manchester and Oxford.

The tomb was discovered during the excavation of a large mound – the Great Tumulus – at Vergina in 1977. Along with many treasures including ceremonial military equipment, bronze utensils, silver tableware, and gold wreaths, the tomb contained two sets of skeletal remains. Those of a man were found in a gold casket in the main chamber and those of a woman in a smaller gold casket in the second chamber. Both individuals had been cremated and evidence of a wooden funerary house containing a pyre was also found near the tomb.

Dr Jonathan Musgrave of the University of Bristol’s Centre for Comparative and Clinical Anatomy and colleagues argue that evidence from the remains is not consistent with historical records of the life, death and burial of Arrhidaios, a far less prominent figure in the ancient world than his father Philip II.

The male skull appears to have a healed fracture on the right cheekbone and a marked asymmetry in the wall of the right maxillary sinus. History records that Philip II lost his right eye at the siege of Methone in 355-4 BC – an injury which would be consistent with this damage to the skeleton.

The colour and fracture lines of the bones suggest they were cremated ‘green’ (with flesh still around them) rather than ‘dry’ (after the flesh had been decomposed by burial). Arrhidaios was murdered in the autumn of 317 BC; his remains, some suggest, were subsequently exhumed and reburied between four and 17 months later. However, the existence of the funeral pyre indicates that the bodies were cremated at Vergina. As Greek beliefs would never have countenanced contact with a decomposing corpse, Arrhidaios would not have been exhumed, moved and then cremated ‘green’.

From the historical account of their deaths and committals, it is thought that Arrhidaios was buried along with his wife Eurydice and her mother Kynna. However, the tomb contains remains from only two individuals. The female remains belong to a woman aged between 20 and 30 whereas Eurydice seems to have been no more than 19 years old when she died.

Dr Musgrave said: “The aim of this paper is not to press the claims of Philip II and his wife Cleopatra but to draw attention to the flaws in those for Philip III Arrhidaios and Eurydice. We do not believe that the condition of the bones and the circumstances of their interment are consistent with descriptions of the funeral of Arrhidaios, his wife and his mother-in-law.”

(Photo: The Yorck Project)

University of Bristol


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Elephants are not bothered by dynamite explosions, but nearby human activity prompts them to dramatically change their behavior, reports a Cornell study that used automated listening devices to monitor elephant behavior in Gabon.

In 2006 the Gabon government granted permission to an energy company to explore for oil by cutting transects and detonating dynamite in Loango National Park. That action outraged environmentalists and led to a moratorium on oil prospecting until June 2007. In March 2007, researchers from Cornell's Elephant Listening Project (ELP) set up 10 automated recording units in the park.

The resulting 27,000 hours of recordings -- obtained between March 2007 and February 2008 -- showed that blasting activity did not cause elephants to leave the area. However, the elephants closest to the human activity near the blasting shifted to a more nocturnal lifestyle, probably in an attempt to avoid the workers.

"Elephants are sensitive to seismic vibrations, and we expected that the dynamite would disturb them [but it didn't]," said Peter Wrege, ELP director and lead author of a paper that was posted online July 27 in the journal Conservation Biology.
An automated recording unit in Loango National Park.

After comparing the recordings of dynamite explosions to thunder, Wrege and colleagues reported that the two sounds may seem similar to elephants and "not something they weren't used to hearing," Wrege said. However, the team reported that the recordings suggest that the sounds of chainsaws felling trees, trucks and workers prompted the elephants to change their behavior to a nighttime routine.

ELP's decision to monitor the elephants in collaboration with the World Conservation Society may have put some pressure on the government and energy company to develop strict operating procedures before prospecting began anew in June 2007, Wrege said. The new protocols required the company to avoid nighttime activities and to limit the size of new transects and the size of trees cut, Wrege added.

The recordings also picked up gunshots in the forest, which have led to patrols through the park to deter poachers, Wrege said.

Resource extraction in developing countries is inevitable, said Wrege, and some industries appear willing to listen to environmental and wildlife concerns, "but often we do not know what the problems are.

"By listening to the natural environment we can reveal hidden but otherwise important relationships between wildlife and humans," said Wrege. "Acoustic technology gives us one more tool in the toolbox that lets us find out things we wouldn't find out in some other way."

(Photo: Ruth Starkey)

Cornell University


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Researchers at the Georgia Institute of Technology have developed a new class of electronic logic device in which current is switched by an electric field generated by the application of mechanical strain to zinc oxide nanowires.

The devices, which include transistors and diodes, could be used in nanometer-scale robotics, nano-electromechanical systems (NEMS), micro-electromechanical systems (MEMS) and microfluidic devices. The mechanical action used to initiate the strain could be as simple as pushing a button, or be created by the flow of a liquid, stretching of muscles or the movement of a robotic component.

In traditional field-effect transistors, an electrical field switches -- or "gates" -- the flow of electrical current through a semiconductor. Instead of using an electrical signal, the new logic devices create the switching field by mechanically deforming zinc oxide nanowires. The deformation creates strain in the nanowires, generating an electric field through the piezoelectric effect -- which creates electrical charge in certain crystalline materials when they are subjected to mechanical strain.

"When we apply a strain to a nanowire placed across two metal electrodes, we create a field, which is strong enough to serve as the gating voltage," said Zhong Lin Wang, a Regents professor in the Georgia Tech School of Materials Science and Engineering. "This type of device would allow mechanical action to be interfaced with electronics, and could be the basis for a new form of logic device that uses the piezoelectric potential in place of a gate voltage."

Wang, who has published a series of articles on the devices in such journals as Nano Letters, Advanced Materials and Applied Physics Letters, calls this new class of nanometer-scale device "piezotronics" because they use piezoelectric potential to tune and gate the charge transport process in semiconductors. The devices rely on the unique properties of zinc oxide nanostructures, which are both semiconducting and piezoelectric.

The transistors and diodes add to the family of nanodevices developed by Wang and his research team, and could be combined into systems in which all components are based on the same zinc oxide material. The researchers have previously announced development of nanometer-scale generators that produce a voltage by converting mechanical motion from the environment, and nanowire sensors for measuring pH and detecting ultraviolet light.

"The family of devices we have developed can be joined together to create self-powered, autonomous and intelligent nanoscale systems," Wang said. "We can create complex systems totally based on zinc oxide nanowires that have memory, processing, and sensing capabilities powered by electrical energy scavenged from the environment."

Using strain-gated transistors fabricated on a flexible polymer substrate, the researchers have demonstrated basic logic operations -- including NOR, XOR and NAND gates and multiplexer/demultiplexer functions -- by simply applying different types of strain to the zinc oxide nanowires. They have also created an inverter by placing strain-gated transistors on both sides of a flexible substrate.

"Using the strain-gated transistor as a building block, we can build complicated logic," Wang added. "This is the first time that a mechanical action has been used to create a logic operation."

A strain-gated transistor is made of a single zinc oxide nanowire with its two ends -- the source and drain electrodes -- fixed to a polymer substrate by metal contacts. Flexing the devices reverses their polarity as the strain changes from compressive to tensile on opposite sides.

The devices operate at low frequencies -- the kind created by human interaction and the ambient environment -- and would not challenge traditional CMOS transistors for speed in conventional applications. The devices respond to very small mechanical forces, Wang noted.

The Georgia Tech group has also learned to control conductivity in zinc oxide nanodevices using laser emissions that take advantage of the unique photo-excitation properties of the material. When ultraviolet light from a laser strikes a metal contact attached to a zinc oxide structure, it creates electron-hole pairs which change the height of the Schottky barrier at the zinc oxide-metal contact.

These conductivity-changing characteristics of the laser emissions can be used in tandem with alterations in mechanical strain to provide more precise control over the conducting capabilities of a device.

"The laser improves the conductivity of the structure," Wang noted. "The laser effect is in contrast to the piezoelectric effect. The laser effect reduces the barrier height, while the piezoelectric effect increases the barrier height."

Wang has called these new devices fabricated by coupling piezoelectric, photon excitation and semiconductor properties "piezo-phototronic" devices.

The research group has also created hybrid logic devices that use zinc oxide nanowires to control current moving through single-walled carbon nanotubes. The nanotubes, which were produced by researchers at Duke University, can be either p-type or n-type.

The research has been supported by the National Science Foundation (NSF), the Defense Advanced Research Projects Agency (DARPA), and the U.S. Department of Energy (DOE). In addition to Wang, the research team includes Wenzhuo Wu, Yaguang Wei, Youfan Hu, Weihua Liu, Minbaek Lee, Yan Zhang, Yanling Chang, Shu Xiang, Lei Ding, Jie Liu and Robert Snyder.

"Our work with strain-gated devices provides a new approach to logic operations that performs mechanical-electrical actions in one structural unit using a single material," Wang noted. "These transistors could provide new processing and memory capabilities in very small and portable devices."

(Photo: GIT)

Georgia Institute of Technology


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UT Southwestern Medical Center researchers have identified unique metabolic properties that allow a specific type of stem cell in the body to survive and replicate in low-oxygen environments.

In a study published in the September issue of the journal Cell Stem Cell, investigators found that the low-oxygen microenvironments that ordinarily deprive and starve other kinds of cells are tolerated by a type of stem cell used as the primary material for bone-marrow transplantation.

These cells, called hematopoietic stem cells, are found in marrow and can replicate quickly. Once transplanted, they eventually develop into blood and other types of cells. Their ability to self-renew before they transform into blood forms the basis of their usefulness for bone-marrow transplants.

“The cells convert glucose, or sugars, into energy rather than using oxygen to release energy,” said Dr. Hesham Sadek, assistant professor of internal medicine at UT Southwestern and senior author of the study. “They use glycolysis instead of mitochondrial oxidative phosphorylation to meet their energy demands.”

Dr. Sadek and his team sought to understand how hematopoietic cells regulate their metabolism in spite of their inhospitable environment and found the cells expressed a certain gene in a way that enabled them to function without using oxygen.

Understanding more about the function of stem cells and their ability to self renew might lead to new avenues of encouraging the cells to grow in large numbers outside the body, Dr. Sadek said. For example, a potential bone-marrow donor’s cells could be incubated and grown indefinitely, providing stem cells to be used in multiple transplant therapies.

“There have been few studies of the metabolism of stem cells, and our aim was to find out how stem cells can ‘breathe’ and replicate without an oxygen-rich environment crucial for other kinds of cells,” Dr. Sadek said.

In addition to being successfully used for bone-marrow transplantation for years, bone-marrow cells are used in hundreds of studies for heart regeneration, he said.

“The findings of this paper highlight important characteristics of bone-marrow stem cells that make them more likely to survive in the low-oxygen environments present, for example, after a heart attack,” Dr. Sadek said. “These findings may also be exploited to enrich bone-marrow stem and progenitor cells by selecting cells based on their metabolic properties.”

(Photo: UTSMC)

UT Southwestern Medical Center


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More hurricanes may form in greener waters, where sunlight tends to be absorbed at shallower depths, than in clear seas, according to new research that draws a link between ocean color and the formation and movement of tropical cyclones.

It’s no secret that hurricanes depend on a recipe of moist air, warm water and converging winds. But in a paper due to be published this month in Geophysical Research Letters, researchers from MIT and the National Oceanic and Atmospheric Administration’s Geophysical Fluid Dynamics Laboratory say ocean color — which is typically influenced by the concentration of tiny marine organisms — may also be a factor.

Ocean color varies around the globe. In the northern Pacific Ocean, the sea surface is dark green because it is packed with sediment and microscopic plants known as phytoplankton that absorb sunlight and keep the ocean’s surface warm. But the crystal-clear waters around the Bahamas lack biological material near the surface, and sunlight is absorbed much deeper. The depth of absorption is important because it affects ocean circulation, and ocean circulation redistributes heat throughout the world’s oceans, thereby affecting sea-surface temperatures.

“For this study, the question was, what difference does two meters versus 20 meters make?” says co-author Kerry Emanuel, the Breene M. Kerr Professor of Atmospheric Science in the Department of Earth, Atmospheric and Planetary Sciences. “We find that the difference is in the pattern of hurricane movement.”

In their analysis, the researchers used computer models to simulate the effects of ocean color on the paths of tropical cyclones — commonly called hurricanes and typhoons. In one simulation, they depleted the phytoplankton in a large region of the North Pacific, which led to cooler sea-surface temperatures. This resulted in a 70 percent decrease in tropical cyclones in the area’s subtropical regions, and a 20 percent increase in tropical cyclones appearing close to the equator. That’s because without phytoplankton, the sea-surface temperature was warmer close to the equator but cooler in the subtropics. As a result, the storms formed closer to the equator where the water was warmer.

“This research underscores how we’re trying to model such a complex system, and how we are probably missing some important physics in those models,” says Jim Kossin, an atmospheric research scientist with NOAA. “Ocean color is one example of that physics.” Although Kossin finds the link between ocean color and tropical cyclones “fascinating,” he points out that because the variability of ocean color isn’t yet well understood, the parameters used in the analysis may not be realistic.

Emanuel cautions against interpreting the study as one that can be used to forecast hurricanes, stressing instead that the research more importantly highlights how closely life in the oceans is linked to the climate system. More than anything, he says, the research provides new impetus for using satellites to monitor ocean color. Although a NASA satellite has done this for about 12 years, budget cuts have threatened its future.

New satellite data would help researchers like lead author Anand Gnanadesikan, an atmospheric scientist with NOAA and lecturer at Princeton, gain a better understanding of how global warming may affect ocean color. This relationship is still unclear, since previous studies have linked global warming to both an increase and a decrease in phytoplankton. “We are very interested in understanding how ocean color might change in the future, and how it might have changed in the past, and seeing whether we can attribute changes in sea-surface temperatures to those changes in ocean color,” he says of future modeling efforts.

(Photo: NASA)

Massachusetts Institute of Technology


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Plants are good at doing what scientists and engineers have been struggling to do for decades: converting sunlight into stored energy, and doing so reliably day after day, year after year. Now some MIT scientists have succeeded in mimicking a key aspect of that process.

One of the problems with harvesting sunlight is that the sun’s rays can be highly destructive to many materials. Sunlight leads to a gradual degradation of many systems developed to harness it. But plants have adopted an interesting strategy to address this issue: They constantly break down their light-capturing molecules and reassemble them from scratch, so the basic structures that capture the sun’s energy are, in effect, always brand new.

That process has now been imitated by Michael Strano, the Charles and Hilda Roddey Associate Professor of Chemical Engineering, and his team of graduate students and researchers. They have created a novel set of self-assembling molecules that can turn sunlight into electricity; the molecules can be repeatedly broken down and then reassembled quickly, just by adding or removing an additional solution. Their paper on the work was published on Sept. 5 in Nature Chemistry.

Strano says the idea first occurred to him when he was reading about plant biology. “I was really impressed by how plant cells have this extremely efficient repair mechanism,” he says. In full summer sunlight, “a leaf on a tree is recycling its proteins about every 45 minutes, even though you might think of it as a static photocell.”

One of Strano’s long-term research goals has been to find ways to imitate principles found in nature using nanocomponents. In the case of the molecules used for photosynthesis in plants, the reactive form of oxygen produced by sunlight causes the proteins to fail in a very precise way. As Strano describes it, the oxygen “unsnaps a tether that keeps the protein together,” but the same proteins are quickly reassembled to restart the process.

This action all takes place inside tiny capsules called chloroplasts that reside inside every plant cell — and which is where photosynthesis happens. The chloroplast is “an amazing machine,” Strano says. “They are remarkable engines that consume carbon dioxide and use light to produce glucose,” a chemical that provides energy for metabolism.

To imitate that process, Strano and his team, supported by grants from the MIT Energy Initiative and the Eni Solar Frontiers Center at MIT, produced synthetic molecules called phospholipids that form disks; these disks provide structural support for other molecules that actually respond to light, in structures called reaction centers, which release electrons when struck by particles of light. The disks, carrying the reaction centers, are in a solution where they attach themselves spontaneously to carbon nanotubes — wire-like hollow tubes of carbon atoms that are a few billionths of a meter thick yet stronger than steel and capable of conducting electricity a thousand times better than copper. The nanotubes hold the phospholipid disks in a uniform alignment so that the reaction centers can all be exposed to sunlight at once, and they also act as wires to collect and channel the flow of electrons knocked loose by the reactive molecules.

The system Strano’s team produced is made up of seven different compounds, including the carbon nanotubes, the phospholipids, and the proteins that make up the reaction centers, which under the right conditions spontaneously assemble themselves into a light-harvesting structure that produces an electric current. Strano says he believes this sets a record for the complexity of a self-assembling system. When a surfactant — similar in principle to the chemicals that BP has sprayed into the Gulf of Mexico to break apart oil — is added to the mix, the seven components all come apart and form a soupy solution. Then, when the researchers removed the surfactant by pushing the solution through a membrane, the compounds spontaneously assembled once again into a perfectly formed, rejuvenated photocell.

“We’re basically imitating tricks that nature has discovered over millions of years” — in particular, “reversibility, the ability to break apart and reassemble,” Strano says. The team, which included postdoctoral researcher Moon-Ho Ham and graduate student Ardemis Boghossian, came up with the system based on a theoretical analysis, but then decided to build a prototype cell to test it out. They ran the cell through repeated cycles of assembly and disassembly over a 14-hour period, with no loss of efficiency.

Strano says that in devising novel systems for generating electricity from light, researchers don’t often study how the systems change over time. For conventional silicon-based photovoltaic cells, there is little degradation, but with many new systems being developed — either for lower cost, higher efficiency, flexibility or other improved characteristics — the degradation can be very significant. “Often people see, over 60 hours, the efficiency falling to 10 percent of what you initially saw,” he says.

The individual reactions of these new molecular structures in converting sunlight are about 40 percent efficient, or about double the efficiency of today’s best solar cells. Theoretically, the efficiency of the structures could be close to 100 percent, he says. But in the initial work, the concentration of the structures in the solution was low, so the overall efficiency of the device — the amount of electricity produced for a given surface area — was very low. They are working now to find ways to greatly increase the concentration.

Philip Collins ’90, associate professor of experimental and condensed-matter physics at the University of California, Irvine, who was not involved in this work, says, “One of the remaining differences between man-made devices and biological systems is the ability to regenerate and self-repair. Closing this gap is one promise of nanotechnology, a promise that has been hyped for many years. Strano's work is the first sign of progress in this area, and it suggests that ‘nanotechnology’ is finally preparing to advance beyond simple nanomaterials and composites into this new realm.”

(Photo: Patrick Gillooly)

Massachusetts Institute of Technology


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In an early step toward letting severely paralyzed people speak with their thoughts, University of Utah researchers translated brain signals into words using two grids of 16 microelectrodes implanted beneath the skull but atop the brain.

"We have been able to decode spoken words using only signals from the brain with a device that has promise for long-term use in paralyzed patients who cannot now speak," says Bradley Greger, an assistant professor of bioengineering.

Because the method needs much more improvement and involves placing electrodes on the brain, he expects it will be a few years before clinical trials on paralyzed people who cannot speak due to so-called "locked-in syndrome."

The Journal of Neural Engineering's September issue is publishing Greger's study showing the feasibility of translating brain signals into computer-spoken words.

The University of Utah research team placed grids of tiny microelectrodes over speech centers in the brain of a volunteer with severe epileptic seizures. The man already had a craniotomy - temporary partial skull removal - so doctors could place larger, conventional electrodes to locate the source of his seizures and surgically stop them.

Using the experimental microelectrodes, the scientists recorded brain signals as the patient repeatedly read each of 10 words that might be useful to a paralyzed person: yes, no, hot, cold, hungry, thirsty, hello, goodbye, more and less.

Later, they tried figuring out which brain signals represented each of the 10 words. When they compared any two brain signals - such as those generated when the man said the words "yes" and "no" - they were able to distinguish brain signals for each word 76 percent to 90 percent of the time.

When they examined all 10 brain signal patterns at once, they were able to pick out the correct word any one signal represented only 28 percent to 48 percent of the time - better than chance (which would have been 10 percent) but not good enough for a device to translate a paralyzed person's thoughts into words spoken by a computer.

"This is proof of concept," Greger says, "We've proven these signals can tell you what the person is saying well above chance. But we need to be able to do more words with more accuracy before it is something a patient really might find useful."

People who eventually could benefit from a wireless device that converts thoughts into computer-spoken spoken words include those paralyzed by stroke, Lou Gehrig's disease and trauma, Greger says. People who are now "locked in" often communicate with any movement they can make - blinking an eye or moving a hand slightly - to arduously pick letters or words from a list.

University of Utah colleagues who conducted the study with Greger included electrical engineers Spencer Kellis, a doctoral student, and Richard Brown, dean of the College of Engineering; and Paul House, an assistant professor of neurosurgery. Another coauthor was Kai Miller, a neuroscientist at the University of Washington in Seattle.

The research was funded by the National Institutes of Health, the Defense Advanced Research Projects Agency, the University of Utah Research Foundation and the National Science Foundation.

The study used a new kind of nonpenetrating microelectrode that sits on the brain without poking into it. These electrodes are known as microECoGs because they are a small version of the much larger electrodes used for electrocorticography, or ECoG, developed a half century ago.

For patients with severe epileptic seizures uncontrolled by medication, surgeons remove part of the skull and place a silicone mat containing ECoG electrodes over the brain for days to weeks while the cranium is held in place but not reattached. The button-sized ECoG electrodes don't penetrate the brain but detect abnormal electrical activity and allow surgeons to locate and remove a small portion of the brain causing the seizures.

Last year, Greger and colleagues published a study showing the much smaller microECoG electrodes could "read" brain signals controlling arm movements. One of the epileptic patients involved in that study also volunteered for the new study.

Because the microelectrodes do not penetrate brain matter, they are considered safe to place on speech areas of the brain - something that cannot be done with penetrating electrodes that have been used in experimental devices to help paralyzed people control a computer cursor or an artificial arm.

EEG electrodes used on the skull to record brain waves are too big and record too many brain signals to be used easily for decoding speech signals from paralyzed people.

In the new study, the microelectrodes were used to detect weak electrical signals from the brain generated by a few thousand neurons or nerve cells.

Each of two grids with 16 microECoGs spaced 1 millimeter (about one-25th of an inch) apart, was placed over one of two speech areas of the brain: First, the facial motor cortex, which controls movements of the mouth, lips, tongue and face - basically the muscles involved in speaking. Second, Wernicke's area, a little understood part of the human brain tied to language comprehension and understanding.

The study was conducted during one-hour sessions on four consecutive days. Researchers told the epilepsy patient to repeat one of the 10 words each time they pointed at the patient. Brain signals were recorded via the two grids of microelectrodes. Each of the 10 words was repeated from 31 to 96 times, depending on how tired the patient was.

Then the researchers "looked for patterns in the brain signals that correspond to the different words" by analyzing changes in strength of different frequencies within each nerve signal, says Greger.

The researchers found that each spoken word produced varying brain signals, and thus the pattern of electrodes that most accurately identified each word varied from word to word. They say that supports the theory that closely spaced microelectrodes can capture signals from single, column-shaped processing units of neurons in the brain.

One unexpected finding: When the patient repeated words, the facial motor cortex was most active and Wernicke's area was less active. Yet Wernicke's area "lit up" when the patient was thanked by researchers after repeating words. It shows Wernicke's area is more involved in high-level understanding of language, while the facial motor cortex controls facial muscles that help produce sounds, Greger says.

The researchers were most accurate - 85 percent - in distinguishing brain signals for one word from those for another when they used signals recorded from the facial motor cortex. They were less accurate - 76 percent - when using signals from Wernicke's area. Combining data from both areas didn't improve accuracy, showing that brain signals from Wernicke's area don't add much to those from the facial motor cortex.

When the scientists selected the five microelectrodes on each 16-electrode grid that were most accurate in decoding brain signals from the facial motor cortex, their accuracy in distinguishing one of two words from the other rose to almost 90 percent.

In the more difficult test of distinguishing brain signals for one word from signals for the other nine words, the researchers initially were accurate 28 percent of the time - not good, but better than the 10 percent random chance of accuracy. However, when they focused on signals from the five most accurate electrodes, they identified the correct word almost half (48 percent) of the time.

"It doesn't mean the problem is completely solved and we can all go home," Greger says. "It means it works, and we now need to refine it so that people with locked-in syndrome could really communicate."

"The obvious next step - and this is what we are doing right now - is to do it with bigger microelectrode grids" with 121 micro electrodes in an 11-by-11 grid, he says. "We can make the grid bigger, have more electrodes and get a tremendous amount of data out of the brain, which probably means more words and better accuracy."

(Photo: Spencer Kellis, The University of Utah)

University of Utah




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