Colloids require a delicate balance of opposing forces for them to be stable: attractive forces must be matched by repulsive ones. A new colloidal stabilization method characterized by scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory may give scientists a new way to control the stability of some colloidal suspensions.

In this approach, known as nanoparticle haloing, highly charged nanoparticles and negligibly charged colloidal microspheres are mixed together in solution. The nanoparticles self-organize around the microspheres to form a halo-like structure that stabilizes the solution. This new pathway to produce materials would not be possible through traditional routes.

The structure of the halo – the key to understanding this kind of stable colloid – has remained a mystery because the nanoparticles that form it are more than 100 times smaller than the microspheres that they surround.

By using x-rays produced by Argonne’s Advanced Photon Source (APS), Argonne scientists, in collaboration with researchers from the University of Illinois at Urbana-Champaign, were able to finally discover the structure of the nanoparticle halo.

The researchers used the ultra-small-angle x-ray scattering (USAXS) instrument at the APS to discover that nanoparticles form a loosely organized layer a small distance from the surface of the microspheres. This discovery suggests a weak attraction between nanoparticle and microsphere, corroborating earlier theoretical predictions that the halo can form only in such an environment.

“Because we have established a methodology to determine the structure of nanoparticle halo, it opens a window to the systematic study of the entire nanoparticle-microsphere phase diagram for this type of novel colloidal stabilization mechanism,” said Argonne’s Fan Zhang, a coauthor on the Langmuir paper.

Contact: Steve McGregor
630-252-5580
DOE/Argonne National Laboratory

Share This

The research, which compared the results of a high-protein, dairy-intensive diet with a conventional weight-loss diet based on the food-guide pyramid, was published in this month’s Journal of Nutrition.

“This is an important finding because many people, especially women in mid-life, are concerned with both obesity and osteoporosis,” said Ellen Evans, a U of I associate professor of kinesiology and community health and member of the U of I Division of Nutritional Sciences.

“Furthermore, treating obesity often increases risk for osteoporosis. Many people lose bone mass when they lose weight,” she said.

Study co-author Donald Layman, a U of I professor of nutrition, has previously reported that protein-rich weight-loss diets preserve muscle mass, help lower blood sugar and lipids, and improve body composition by targeting weight carried in the abdomen.

In the recent study, Layman’s diet prescribed approximately 30 percent of all calories from protein, with an emphasis on lean meats and low-fat dairy products.

The scientists recruited and randomized 130 middle-aged, overweight persons at two sites—the U of I and Pennsylvania State University. Participants then followed either the higher-protein weight-loss diet or a conventional higher-carbohydrate weight-loss diet based on the food-guide pyramid for four months of active weight loss followed by eight months of weight maintenance.

“Essentially we substituted lean meats and low-fat milk, cheese, yogurt, etc., for some of the high-carbohydrate foods in the food-pyramid diet. Participants also ate five servings of vegetables and two to three servings of fruit each day,” Evans said.

Bone mineral content and density were measured with DXA scans of the whole body, lumbar spine, and hip at the beginning of the study, at four months, at eight months, and at the end of the 12-month period.

“In the higher-protein group, bone density remained fairly stable, but bone health declined over time in the group that followed the conventional higher-carbohydrate diet. A statistically significant treatment effect favored the higher-protein diet group,” said Matthew Thorpe, a medical scholars (MD/PhD) student who works in Evans’s lab and was the primary author of the study.

“The combination and/or interaction of dietary protein, calcium from dairy, and the additional vitamin D that fortifies dairy products appears to protect bone health during weight loss,” he added.

Because higher-protein diets have been associated with elevated urinary calcium levels, some scientists have feared that these diets cause bone demineralization.

The U of I team measured these levels at the beginning and eight months into the study. Although the researchers did note increased amounts of urinary calcium in the higher-protein group, they attributed the source of the increased calcium to improved intestinal absorption of calcium rather than bone loss.

“Other recent studies using radiolabeled calcium have shown that the higher urinary calcium levels associated with higher-protein diets are not coming from bone as some researchers had believed,” Thorpe said.

The U of I scientists will soon begin a similar study contrasting higher-protein, dairy-rich diets with conventional weight-loss diets in older, mildly frail women.

“We’ll measure bone and muscle outcomes in the two groups after six months of weight loss. Ultimately we want to know if a higher-protein weight-loss diet that emphasizes lean meats, whey protein, and low-fat dairy consumption can reduce the risk for osteoporosis and muscle loss.

“We also want to learn how these changes in body composition will affect balance, gait, and other measures of physical function in this population known to be at high risk for osteoporosis and physical disability,” she said.

Contact: Phyllis Picklesimer
217-244-2827
University of Illinois at Urbana-Champaign

Share This

Two papers in the June 6, 2008, issue of the journal Molecular Cell, published by Cell Press, describe advances in understanding Pol II copying fidelity. The papers are by Craig Kaplan of Stanford University and his colleagues; and Mikhail Kashlev of the National Cancer Institute Center for Cancer Research and his colleagues.

The researchers said their findings not only offer unprecedented details about the fidelity mechanism of Pol II, but likely about fidelity in all cellular genetic copying machines. They said their discoveries also offer understanding of how defective Pol II can generate errors in transcribing mRNA—errors that can promote cancer formation. Both groups concentrated on the function of the Pol II “active site” region, where the enzyme captures an RNA component, called a nucleosidetriphosphate (NTP), and chemically attaches it to the RNA chain. Although Pol II uses the DNA genetic sequence as a template to specify the RNA sequence, another largely unknown fidelity mechanism exists by which Pol II discriminates against incorrect NTPs. This fidelity mechanism is extremely precise; it can distinguish the NTPs that make up RNA from the deoxyNTPs used in DNA—although the two molecules differ only in one small chemical group.

In their paper, Kaplan and colleagues explored a key component of the active site known as the “trigger loop.” This small bit of protein is highly mobile, and although researchers have believed that it plays a critical function in discriminating the correct NTP, that function was poorly understood.

In studies with yeast, Kaplan and his colleagues produced a mutant form of Pol II with a subtly crippled trigger loop. This mutation substituted one amino acid with another in what was believed to be a key position in the trigger loop, His 1085, for interacting with incoming NTPs to discriminate the correct one. The researchers compared the detailed molecular function of normal and His 1085 mutant Pol II enzymes during the encounter with both correct and incorrect NTPs. They also compared the behavior of the mutant with the action of the mushroom toxin alpha-amanitin, which is theorized to block Pol II by interfering with the trigger loop. The researchers’ studies of the mutant and alpha-amanitin revealed crucial details showing how the trigger loop determines fidelity, said Kaplan.

“We found that the amanitin-treated wild-type enzyme behaved very similar to our mutant enzyme,” said Kaplan. In fact, he said, the experiments, as well as structural information on the active site, indicated that alpha-amanitin targets the same His 1085 position in the trigger loop as does their mutation. Kaplan concluded that the findings reveal a specific and critical role for the trigger loop.

“These findings reveal what is called a ‘kinetic selection’ mechanism for Pol II, which is like many polymerases,” he said. “That is, the active site in one condition has a similar affinity for both correct and incorrect NTPs. However, because of motion within the active site—in this case the action of the trigger loop—catalytic activity in the active site proceeds much faster with the correct NTP than with the incorrect NTP. The trigger loop is mobile, and only when it is positioned properly in response to a correct substrate can it really function.

“We think this mode of substrate recognition is a general theme for systems that have to select the right molecule out of a giant pool of the wrong molecules,” said Kaplan. An example, he said, is when the protein-making ribosomal machinery must select the correct transfer RNA from among similar-but-incorrect transfer RNAs.

Besides Kaplan, other co-authors on the paper were Karl-Magnus Larsson and Roger Kornberg.

In the other Molecular Cell paper, Kashlev and colleagues used a different yeast mutant to explore the function of the Pol II active site. In their screen for Pol II mutants, they identified one, E1103G, that shows a several-fold increase in error rate over the normal, wild-type Pol II.

Importantly, said Kashlev, the researchers could precisely measure the transcription error rate using a new assay, called a retrotransposition assay, developed by co-author Jeffrey Strathern.

The researchers’ analysis of the effects of E1103G yielded significant insights into the function of the trigger loop, said Kashlev.

“Normally, when an NTP diffuses into the active site of the polymerase, the trigger loop closes behind it like a door, long enough for the polymerase to perform the chemistry to add the NTP to the end of the RNA chain,” he said. “If the NTP is incorrect, there is a tendency for this door to stay open for a longer time, which means that the NTP has a chance to diffuse out of the active site before the polymerase can proceed to chemistry.

“Our mutation occupies a strategic position important for keeping the loop open, like a latch,” said Kashlev. “So, in the mutant, the door wants to stay in the closed state for a longer time, which means if an incorrect NTP migrates into the active site, there is time for the polymerase to add this incorrect NTP to the RNA chain.”

Kashlev said the motivation for their studies of Pol II transcription fidelity is to understand the effects of Pol II errors on genome stability. Specifically, error-prone Pol II could generate mRNA that produces aberrant versions of the critical enzyme DNA polymerase. As DNA polymerase is responsible for gene replication, the result of its malfunction could be a burst of gene mutation causing an “error catastrophe” that could lead to genome instability and cancer formation.

Contact: Cathleen Genova
617-397-2802
Cell Press

Share This

Research in the University of Alberta’s Faculty of Science may soon be able to answer that question. The departments of computing science and earth and atmospheric science have been working together to create a Wireless Sensor Network that allows for the clandestine data collection of environmental factors in remote locations and its monitoring from anywhere in the world where the Internet is available.

The research team, including Pawel Gburzynski, Mario Nascimento, and Arturo Sanchez-Azofeifa, recently launched EcoNet, a functional model of a WSN for environmental monitoring in the display house in the University of Alberta’s Agriculture/Forestry Centre. The display house hosts a small but feature-rich environment that mimics that of a tropical forest. Using a WSN, a number of sensors can continuously monitor factors like temperature and luminosity and will process, store and transmit data co-operatively and wirelessly with other sensors to generate data that can then be collected and made available to users virtually anywhere on the globe. The sensors represent a technology for researchers to monitor diverse phenomena continuously and inconspicuously.

Having the data continuously monitored by researchers substantially increases the chances of uncovering anomalies early enough to investigate them promptly and thoroughly.

The overall framework of WSN can also be extended for use in other closely related scenarios such as monitoring potentially dangerous situations like hazardous waste disposal, or hard-to-witness phenomena such as ice cap movements in the Arctic.

The opportunities these sensors will provide to scientists are paramount in a global environment that is changing at an ever-increasing pace.

Once the display-house prototype is tested and customized, at least two sites are to be fully deployed in the fall, one likely in the Brazilian rainforest, and the other in a forest in Panama.

Contact: Bev Betkowski
780-492-3808
University of Alberta

Share This

In an article published today in the journal Nature, the team, led by Chia-Ling Chien, the Jacob L. Hain Professor of Physics and director of the Material Research Science and Engineering Center at The Johns Hopkins University, offers insights into why the characteristics of a new family of iron-based superconductors reveal the need for fresh theoretical models which could, they say, pave the way for the development of superconductors that can operate at room temperature.

“It appears to us that the new iron-based superconductors disclose a new physics, contain new mysteries and may start us along an uncharted pathway to room temperature superconductivity,” said Chien, who teamed up on the research with Tingyong Chen and Zlatko Tesanovic, both of Johns Hopkins, and X.H. Chen and R.H. Liu of the Hefei National Laboratory for Physical Science at Microscale and Department of Physics, University of Science and Technology of China in Anhui, China.

Superconductors are materials that can carry electrical current without friction and as a result, don’t waste electrical energy generating heat. (Imagine your laptop computer or PC not getting warm when it is turned on.) This means that an electrical current can flow in a loop of superconducting wire forever without a power source. Today, superconductors are used in hospital MRI machines, as filters in cell phone base stations and in high-speed magnetic levitating trains. Unfortunately, most of today’s superconducting materials can only function and operate at extremely low temperatures, which means that they must be paired with expensive supercooling equipment. This presents researchers with a grand challenge: to find superconducting material that can operate at more “normal” temperatures.

“If superconductors could exist at room temperatures, the world energy crisis would be solved,” Chen said.

Chen explains that though all metals contain mobile electrons which conduct electricity, a metal becomes a superconductor only when two electrons with opposite “spins” are paired. The superconductor energy “gap,” which is the amount of energy that would be needed to break the bond between two electrons forming such a pair to release them from one another, determines the robustness or strength of the superconducting state. This energy gap is highest at low temperatures, but vanishes at the temperatures at which superconductivity ceases to exist.

“This gap — its structure and temperature dependence — reveal the ’soul’ of the superconductor, and this is what was measured in our experiment,” Chien said.

The team measured this gap and its temperature variation, revealing that the pairing mechanism in iron-based superconductors is different from the one in more traditional, copper-based, high-temperature superconductors. To the researchers’ surprise, their results were incompatible with some of the newly proposed theories in this mushrooming field.

“In the face of this discovery, it is clear that we need to reexamine the old and invent some new theoretical models,” Tesanovic said. “I predict that these new, iron-based superconductors will keep us physicists busy for a long, long while.”

Contact: Lisa DeNike
443-287-9960
Johns Hopkins University

Share This

The method automatically detects within minutes when an Internet worm has infected a computer network.

Network administrators can then isolate infected machines and hold them in quarantine for repairs.

Ness Shroff, Ohio Eminent Scholar in Networking and Communications at Ohio State University, and his colleagues describe their strategy in the current issue of IEEE Transactions on Dependable and Secure Computing.

They discovered how to contain the most virulent kind of worm: the kind that scans the Internet randomly, looking for vulnerable hosts to infect.

“These worms spread very quickly,” Shroff said. “They flood the Net with junk traffic, and at their most benign, they overload computer networks and shut them down.”

Code Red was a random scanning worm, and it caused $2.6 billion in lost productivity to businesses worldwide in 2001. Even worse, Shroff said, the worm blocked network traffic to important physical facilities such as subway stations and 911 call centers.

“Code Red infected more than 350,000 machines in less than 14 hours. We wanted to find a way to catch infections in their earliest stages, before they get that far,” Shroff said.

The key, they found, is for software to monitor the number of scans that machines on a network send out. When a machine starts sending out too many scans — a sign that it has been infected — administrators should take it off line and check it for viruses.

The strategy sounds straightforward enough. A scan is just a search for Internet addresses — what we do every time we use search engines such as Google. The difference is, a virus sends out many scans to many different destinations in a very short period of time, as it searches for machines to infect.

“The difficulty was figuring out how many scans were too many,” Shroff said. “How many could you allow before an infection would spread wildly? You want to make sure the number is small to contain the infection. But if you make it too small, you’ll interfere with normal network traffic.”

“It turns out that you can allow quite a large number of scans, and you’ll still catch the worm.”

Shroff was working at Purdue University in 2006 when doctoral student Sarah Sellke suggested making a mathematical model of the early stages of worm growth. With Saurabh Bagchi, assistant professor of electrical and computer engineering at Purdue, they developed a model that calculated the probability that a virus would spread, depending on the maximum number of scans allowed before a machine was taken off line.

In simulations, they pitted their model against the Code Red worm, as well as the SQL Slammer worm of 2003. They simulated how far the virus would spread, depending on how many networks on the Internet were using the same containment strategy: quarantine any machine that sends out more than 10,000 scans.

They chose 10,000 because it is well above the number of scans that a typical computer network would send out in a month.

“An infected machine would reach this value very quickly, while a regular machine would not,” Shroff explained. “A worm has to hit so many IP addresses so quickly in order to survive.”

In the simulations pitted against the Code Red worm, they were able to prevent the spread of the infection to less than 150 hosts on the whole Internet, 95 percent of the time.

A variant of Code Red worm (Code Red II) scans the local network more efficiently, and finds vulnerable targets much faster. Their method was effective in containing such worms. In the simulations, they were able to trap the worm in its original network — the one that would have started the outbreak — 77 percent of the time.

Anywhere from 10 to 20 percent of the time, it spread to one other network, but no further. The remaining 3 to 13 percent of the time, it escaped to more networks, but the infection was slowed.

In all cases, there was a dramatic decrease in the spread of the worm within the first hour.

To use this strategy, network administrators would have to install software to monitor the number of scans on their networks, and would have to allow for some downtime among computers when they initiate a quarantine.

According to Shroff, that wouldn’t be a problem for most organizations. Very small businesses — ones with only a few servers — may have more difficulty taking their machines off line.

“Unfortunately there is no complete foolproof solution,” Shroff said. “You just keep trying to come up with techniques that limit a virus’s ability to do harm.”

He and his colleagues are working on adapting their strategy to stop targeted Internet worms — ones that have been designed specifically to attack certain vulnerable IP addresses.

Contact: Ness Shroff
614-247-6554
Ohio State University

Share This

Berkeley — As the cost of sequencing a single human genome drops rapidly, with one company predicting a price of $100 per person in five years, soon the only reason not to look at your “personal genome” will be fear of what bad news lies in your genes.

University of California, Berkeley, scientists, however, have found a welcome reason to delve into your genetic heritage: to find the slight genetic flaws that can be fixed with remedies as simple as vitamin or mineral supplements.

“I’m looking for the good news in the human genome,” said Jasper Rine, UC Berkeley professor of molecular and cell biology.

“Headlines for the last 20 years have really been about the triumph of biomedical research in finding disease genes, which is biologically interesting, genetically important and frightening to people who get this information,” Rine said. “I became obsessed with trying to decide if there is some other class of information that will make people want to look at their genome sequence.”

What Rine and colleagues found and report this week in the online early edition of the journal Proceedings of the National Academy of Sciences (PNAS) is that there are many genetic differences that make people’s enzymes less efficient than normal, and that simple supplementation with vitamins can often restore some of these deficient enzymes to full working order.

First author Nicholas Marini, a UC Berkeley research scientist, noted that physicians prescribe vitamins to “cure” many rare and potentially fatal metabolic defects caused by mutations in critical enzymes. But those affected by these metabolic diseases are people with two bad copies, or alleles, of an essential enzyme. Many others may be walking around with only one bad gene, or two copies of slightly defective genes, throwing their enzyme levels off slightly and causing subtle effects that also could be eliminated with vitamin supplements.

“Our studies have convinced us that there is a lot of variation in the population in these enzymes, and a lot of it affects function, and a lot of it is responsive to vitamins,” Marini said. “I wouldn’t be surprised if everybody is going to require a different optimal dose of vitamins based on their genetic makeup, based upon the kind of variance they are harboring in vitamin-dependent enzymes.”

Though this initial study tested the function of human gene variants by transplanting them into yeast cells, where the function of the variants can be accurately assessed, Rine and Marini are confident the results will hold up in humans. Their research, partially supported by the Defense Advanced Research Projects Agency (DARPA) and the U.S. Army, may enable them to employ U.S. soldiers to test the theory that vitamin supplementation can tune up defective enzymes.

“Our soldiers, like top athletes, operate under extreme conditions that may well be limited by their physiology,” Rine said. “We’re now working with the defense department to identify variants of enzymes that are remediable, and ultimately hope to identify troops that have these variants and test whether performance can be enhanced by appropriate supplementation.”

In the PNAS paper, Rine, Marini and their colleagues report on their initial analysis of variants of a human enzyme called methylenetetrahydrofolate reductase, or MTHFR. The enzyme, which requires the B vitamin folate to work properly, plays a key role in synthesizing molecules that go into the nucleotide building blocks of DNA. Some cancer drugs, such as methotrexate, target MTHFR to shut down DNA synthesis and prevent tumor growth.

Using DNA samples from 564 individuals of many races and ethnicities, colleagues at Applied Biosystems of Foster City, Calif., sequenced for each person the two alleles that code for the MTHFR enzyme. Consistent with earlier studies, they found three common variants of the enzyme, but also 11 uncommon variants, each of the latter accounting for less than one percent of the sample.

They then synthesized the gene for each variant of the enzyme, and Marini, Rine and their UC Berkeley colleagues inserted these genes into separate yeast cells in order to judge the activity of each variant. Yeast use many of the same enzymes and cofactor vitamins and minerals as humans and are an excellent model for human metabolism, Rine said.

The researchers found that four different mutations affected the functioning of the human enzyme in yeast. One of these mutations is well known: Nearly 30 percent of the population has one copy, and nine percent has two copies.

The researchers were able to supplement the diet of the cultured yeast with folate, however, and restore full functionality to the most common variant, and to all but one of the less common variants.

Since this experiment, the researchers have found 30 other variants of the MTHFR enzyme and tested about 15 of them, “and more than half interfere with the function of the enzyme, producing a hundred-fold range of enzyme activity. The majority of these can be either partially or completely restored to normal activity by adding more folate. And that is a surprise,” Rine said.

Most scientists think that harmful mutations are disfavored by evolution, but Rine pointed out that this applies only to mutations that affect reproductive fitness. Mutations that affect our health in later years are not efficiently removed by evolution and may remain in our genome forever.

The health effects of tuning up this enzyme in humans are unclear, he said, but folate is already known to protect against birth defects and seems to protect against heart disease and cancer. At least one defect in the MTHFR enzyme produces elevated levels in the blood of the metabolite homocysteine, which is linked to an increased risk of heart disease and stroke, conditions that typically affect people in their post-reproductive years.

“In those people, supplementation of folate in the diet can reduce levels of that metabolite and reduce disease risk,” Marini said.

Marini and Rine estimate that the average person has five rare mutant enzymes, and perhaps other not-so-rare variants, that could be improved with vitamin or mineral supplements.

“There are over 600 human enzymes that use vitamins or minerals as cofactors, and this study reports just what we found by studying one of them,” Rine said. “What this means is that, even if the odds of an individual having a defect in one gene is low, with 600 genes, we are all likely to have some mutations that limit one or more of our enzymes.”

The subtle effects of variation in enzyme activity may well account for conflicting results of some clinical trials, including the confusing data on the effect of vitamin supplements, he noted. In the future, the enzyme profile of research subjects will have to be taken into account in analyzing the outcome of clinical trials.

If one considers not just vitamin-dependent enzymes but all the 30,000 human proteins in the genome, “every individual would harbor approximately 250 deleterious substitutions considering only the low-frequency variants. These numbers suggest that the aggregate incidence of low-frequency variants could have a significant physiological impact,” the researchers wrote in their paper.

All the more reason to poke around in one’s genome, Rine said.

“If you don’t give people a reason to become interested in their genome and to become comfortable with their personal genomic information, then the benefits of much of the biomedical research, which is indexed to particular genetic states, won’t be embraced in a time frame that most people can benefit from,” Rine said. “So, my motivation is partly scientific, partly an education project and, in some ways, a partly political project.”

Marini and Rine credit Bruce Ames, a UC Berkeley professor emeritus of molecular and cell biology now on the research staff at Children’s Hospital Oakland Research Institute, with the research that motivated them to look at enzyme variation. Ames found in the 1970s that many bacteria that could not produce a specific amino acid could do so if given more vitamin B6, and in recent years he has continued exploring the link between micronutrients and health.

“Looked at in one way, Bruce found that you can cure a genetic disease in bacteria by treating it with vitamins,” Rine said. Because the human genome contains about 6 billion DNA base pairs, each one subject to mutation, there could be between 3 and 6 million DNA sequence differences between any two people. Given those numbers, he reasoned that, as in bacteria, “there should be people who are genetically different in terms of the amount of vitamin needed for optimal performance of their enzymes.”

This touches on what Rine considers one of the key biomedical questions today. “Now that we have the complete genome sequences of all the common model organisms, including humans, it’s obvious that the defining challenge of biology in the 21st century is not what the genes are, but what the variation in the genes does,” he said.

Rine, Marini and their colleagues are continuing to study variation in the human MTHFR gene as well as other folate utilizing enzymes, particularly with respect to how defects in these enzymes may lead to birth defects. Rine also is taking advantage of the 1,500 students in his Biology 1A lab course to investigate variants of a second vitamin B6-dependent enzyme, cystathionine beta-synthase.

He also is investigating how enzyme cofactors like vitamins and minerals fix defective enzymes. He suspects that supplements work by acting as chaperones to stabilize the proper folding of the enzyme, which is critical to its catalytic activity. “That is a new principle that may be applicable to drug design,” Rine said.

Contact: Robert Sanders
510-643-6998
University of California - Berkeley

Share This

For centuries, the concept of mind readers was strictly the domain of folklore and science fiction. But according to new research published today in the journal Science, scientists are closer to knowing how specific thoughts activate our brains. The findings demonstrate the power of computational modeling to improve our understanding of how the brain processes information and thoughts.

The research was conducted by a computer scientist, Tom Mitchell, and a cognitive neuroscientist, Marcel Just, both of Carnegie Mellon University. Their previous research, supported by the National Science Foundation (NSF) and the W.M. Keck Foundation, had shown that functional magnetic resonance imaging (fMRI) can detect and locate brain activity when a person thinks about a specific word. Using this data, the researchers developed a computational model that enabled a computer to correctly determine what word a research subject was thinking about by analyzing brain scan data.

In their most recent work, Just and Mitchell used fMRI data to develop a more sophisticated computational model that can predict the brain activation patterns associated with concrete nouns, or things that we experience through our senses, even if the computer did not already have the fMRI data for that specific noun.

The researchers first built a model that took the fMRI activation patterns for 60 concrete nouns broken down into 12 categories including animals, body parts, buildings, clothing, insects, vehicles and vegetables. The model also analyzed a text corpus, or a set of texts that contained more than a trillion words, noting how each noun was used in relation to a set of 25 verbs associated with sensory or motor functions. Combining the brain scan information with the analysis of the text corpus, the computer then predicted the brain activity pattern of thousands of other concrete nouns.

In cases where the actual activation patterns were known, the researchers found that the accuracy of the computer model’s predictions was significantly better than chance. The computer can effectively predict what each participant’s brain activation patterns would look like when each thought about these words, even without having seen the patterns associated with those words in advance.

“We believe we have identified a number of the basic building blocks that the brain uses to represent meaning,” said Mitchell. “Coupled with computational methods that capture the meaning of a word by how it is used in text files, these building blocks can be assembled to predict neural activation patterns for any concrete noun. And we have found that these predictions are quite accurate for words where fMRI data is available to test them.”

Just said the computational model provides insight into the nature of human thought. “We are fundamentally perceivers and actors,” he said. “So the brain represents the meaning of a concrete noun in areas of the brain associated with how people sense it or manipulate it. The meaning of an apple, for instance, is represented in brain areas responsible for tasting, for smelling, for chewing. An apple is what you do with it. Our work is a small but important step in breaking the brain’s code.”

In addition to representations in these sensory-motor areas of the brain, the Carnegie Mellon researchers found significant activation in other areas, including frontal areas associated with planning functions and long-term memory. When someone thinks of an apple, for instance, this might trigger memories of the last time the person ate an apple, or initiate thoughts about how to obtain an apple.

“This suggests a theory of meaning based on brain function,” Just added.

The work could eventually lead to the use of brain scans to identify thoughts and could have applications in the study of autism, disorders of thought such as paranoid schizophrenia, and semantic dementias such as Pick’s disease.

Officials at NSF say they are excited and intrigued by these findings. “This has been an interesting project to watch,” said Kenneth Whang, a program officer at NSF who is responsible for the grant to Mitchell and Just. “They started with some fundamental ideas from machine learning about how to get the most out of fMRI data, and now they’ve not only shown the power of their computational approach, but also made headway on one of the most important problems in the understanding of language in the brain.”

Whang believes that Mitchell and Just’s research will stimulate further research in the field of computational neuroscience. “This opens up all sorts of new possibilities for looking into the fine structure of how patterns of brain activity relate to human thought processes.”

Contact: Dana W. Cruikshank
703-292-8070
National Science Foundation

Share This

Fractional electron charges were first predicted over 20 years ago under conditions existing in the so-called quantum Hall effect, and were found by the Weizmann group some ten years ago. Although electrons are indivisible, if they are confined to a two-dimensional layer inside a semiconductor, chilled down to a fraction of a degree above absolute zero and exposed to a strong magnetic field that is perpendicular to the layer, they effectively behave as independent particles, called quasiparticles, with charges smaller than that of an electron. But until now, these charges had always been fractions with odd denominators: one third of an electron, one fifth, etc.

The experiment done by research student Merav Dolev in Prof. Moty Heiblum’s group, in collaboration with Drs. Vladimir Umansky and Diana Mahalu, and Prof. Ady Stern, all of the Condensed Matter Physics Department, owes the finding of quarter-charge quasiparticles to an extremely precise setup and unique material properties: The gallium arsenide material they produced for the semiconductor was some of the purest in the world. The scientists tuned the electron density in the two-dimensional layer – in which about three billion electrons were confined in the space of a square millimeter – such that there were five electrons for every two magnetic field fluxes. The device they created is shaped like a flattened hourglass, with a narrow ‘waist’ in the middle that allows only a small number of charge-carrying particles to pass through at a time. The ’shot noise’ produced when some passed through and others bounced back caused fluctuations in the current that are proportional to the passing charges, thus allowing the scientists to accurately measure the quasiparticles’ charge.

Quarter-charge quasiparticles should act quite differently from odd fractionally charged particles, and this is why they have been sought as the basis of the theoretical ‘topographical quantum computer.’ When particles such as electrons, photons, or even those with odd fractional charges change places with one another, there is little overall effect. In contrast, quarter-charge particle exchanges might weave a ‘braid’ that preserves information on the particles’ history. To be useful for topologically-based quantum computers, the quarter-charge particles must be shown to have ‘non-Abelian’ properties – that is the order of the braiding must be significant. These subtle properties are extremely difficult to observe. Heiblum and his team are now working on devising experimental setups to test for these properties.

Contact: Yivsam Azgad
972-893-43856
Weizmann Institute of Science

Share This

HOUSTON — May 29, 2008 — In a development that could lead to new technologies for cleaning up oil spills and polluted groundwater, scientists at Rice University have shown how tiny, stick-shaped particles of metal and carbon can trap oil droplets in water by spontaneously assembling into bag-like sacs.

The tiny particles were found to assemble spontaneously by the tens of millions into spherical sacs as large as BB pellets around droplets of oil in water. In addition, the scientists found that ultraviolet light and magnetic fields could be used to flip the nanoparticles, causing the bags to instantly turn inside out and release their cargo — a feature that could ultimately be handy for delivering drugs.

“The core of the nanotechnology revolution lies in designing inorganic nanoparticles that can self-assemble into larger structures like a ’smart dust’ that performs different functions in the world – for example, cleaning up pollution,” said lead research Pulickel Ajayan, Rice’s Benjamin M. and Mary Greenwood Anderson Professor in Mechanical Engineering and Materials Science. “Our approach brings the concept of self-assembling, functional nanomaterials one step closer to reality.”

The research was published online today by the American Chemical Society’s journal Nano Letters.

The multisegmented nanowires, akin to “nanoscale batons,” were made by connecting two nanomaterials with different properties, much like an eraser is attached to the end of a wooden pencil. In the study, the researchers started with carbon nanotubes — hollow tubes of pure carbon. Atop the nanotubes, they added short segments of gold. Ajayan said that by adding various other segments — like sections of nickel or other materials — the researchers can create truly multifunctional nanostructures.

The tendency of these nanobatons to assemble in water-oil mixtures derives from basic chemistry. The gold end of the wire is water-loving, or hydrophilic, while the carbon end is water-averse, or hydrophobic. The thin, water-tight sacs that surround all living cells are formed by interlocking arrangements of hydrophilic and hydrophobic chemicals, and the sac-like structures created in the study are very similar.

Ajayan, graduate student Fung Suong Ou and postdoctoral researcher Shaijumon Manikoth demonstrated that oil droplets suspended in water became encapsulated because of the structures’ tendency to align their carbon ends facing the oil. By reversing the conditions — suspending water droplets in oil – the team was able to coax the gold ends to face inward and encase the water.

“For oil droplets suspended in water, the spheres give off a light yellow color because of the exposed gold ends,” Ou said. “With water droplets, we observe a dark sphere due to the protruding black nanotubes.”

The team is next preparing to test whether chemical modifications to the “nanobatons” could result in spheres that can both capture and break down oily chemicals. For example, they hope to attach catalysts to the water-hating ends of the nanowires that will cause compounds like trichloroethene, or TCE, to break into nontoxic constituents. Another option would be to attach drugs whose release can be controlled with an external stimulus.

“The idea is to go beyond just capturing the compound and initiate a process that will make it less toxic,” Ajayan said. “We want to build upon the method of self assembly and start adding functionality so these particles can carry out tasks in the real world.”

The research was supported by Rice University, Applied Materials Inc. and the New York State Foundation for Science, Technology and Innovation.

Contact: Jade Boyd
713-348-6778
Rice University

Share This