Georgia Tech School of Chemistry and Biochemistry postdoctoral fellow Chiaolong Hsiao (left) and professor Loren Williams examine on a light box a polyacrylamide gel surrounded by an iron solution to determine whether RNA is stable in the iron solution. (Click image for high-resolution version. Credit: Gary Meek)

The study shows that RNA is capable of catalyzing electron transfer under conditions similar to those of the early Earth. Because electron transfer, the moving of an electron from one chemical species to another, is involved in many biological processes – including photosynthesis, respiration and the reduction of RNA to DNA – the study’s findings suggest that complex biochemical transformations may have been possible when life began.

There is considerable evidence that the evolution of life passed through an early stage when RNA played a more central role, before DNA and coded proteins appeared. During that time, more than 3 billion years ago, the environment lacked oxygen but had an abundance of soluble iron.

“Our study shows that when RNA teams up with iron in an oxygen-free environment, RNA displays the powerful ability to catalyze single electron transfer, a process involved in the most sophisticated biochemistry, yet previously uncharacterized for RNA,” said Loren Williams, a professor in the School of Chemistry and Biochemistry at the Georgia Institute of Technology.

The results of the study were published online on May 19, 2013, in the journal Nature Chemistry. The study was sponsored by the NASA Astrobiology Institute, which established the Center for Ribosomal Origins and Evolution (Ribo Evo) at Georgia Tech.

Free oxygen gas was almost nonexistent in the Earth’s atmosphere more than 3 billion years ago. When free oxygen began entering the environment as a product of photosynthesis, it turned the earth’s iron to rust, forming massive banded iron formations that are still mined today. The free oxygen produced by advanced organisms caused iron to be toxic, even though it was – and still is – a requirement for life. Williams believes the environmental transition caused a slow shift from the use of iron to magnesium for RNA binding, folding and catalysis.

Georgia Tech School of Chemistry and Biochemistry postdoctoral fellow Chiaolong Hsiao (left) and professor Loren Williams examine on a light box a polyacrylamide gel surrounded by an iron solution to determine whether RNA is stable in the iron solution. (Click image for high-resolution version. Credit: Gary Meek)

Williams and Georgia Tech School of Chemistry and Biochemistry postdoctoral fellow Chiaolong Hsiao used a standard peroxidase assay to detect electron transfer in solutions of RNA and either the iron ion, Fe2+, or magnesium ion, Mg2+. For 10 different types of RNA, the researchers observed catalysis of single electron transfer in the presence of iron and absence of oxygen. They found that two of the most abundant and ancient types of RNA, the 23S ribosomal RNA and transfer RNA, catalyzed electron transfer more efficiently than other types of RNA. However, none of the RNA and magnesium solutions catalyzed single electron transfer in the oxygen-free environment.

“Our findings suggest that the catalytic competence of RNA may have been greater in early Earth conditions than in present conditions, and our experiments may have revived a latent function of RNA,” added Williams, who is also director of the Ribo Evo Center.

This new study expands on research published in May 2012 in the journal PLoS ONE. In the previous work, Williams led a team that used experiments and numerical calculations to show that iron, in the absence of oxygen, could substitute for magnesium in RNA binding, folding and catalysis. The researchers found that RNA’s shape and folding structure remained the same and its functional activity increased when magnesium was replaced by iron in an oxygen-free environment.

In future studies, the researchers plan to investigate whether other unique functions may have been conferred on RNA through interaction with a variety of metals available on the early Earth.

In addition to Williams and Hsiao, Georgia Tech School of Biology professors Roger Wartell and Stephen Harvey, and Georgia Tech School of Chemistry and Biochemistry professor Nicholas Hud, also contributed to this work as co-principal investigators in the Ribo Evo Center at Georgia Tech.

This work was supported by NASA (Award No. NNA09DA78A). The content is solely the responsibility of the principal investigators and does not necessarily represent the official views of NASA.

CITATION: Chiaolong Hsiao, et al., “RNA with iron(II) as a cofactor catalyses electron transfer,” (Nature Chemistry, 2013). http://dx.doi.org/10.1038/nchem.1649

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Georgia Institute of Technology
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Media Relations Contact: John Toon (404-894-6986)(jtoon@gatech.edu).

Writer: Abby Robinson

Scientists and engineers at Georgia Tech are applying their expertise, tools and techniques to address questions like these – and to explore on a fundamental level how the brain works.

School of Applied Physiology assistant professor Lewis Wheaton (right) and graduate student Nikhilesh Natraj examine neural activation patterns in the brain that are associated with seeing tools in context. (Click image for high-resolution version. Credit: Gary Meek)

Because the human brain is immensely complex, the researchers are pursuing many levels of inquiry – from molecules to cells to circuits to the mystery of the mind itself – and also studying brain disorders and development, along with daily feats of brain activity, such as vision, speech, movement and memory.

Georgia Tech researchers are also developing better interventions for brain injuries and disorders. They are designing tools to help neuroscientists better probe and record the activity of neurons in tissue samples and living animals. And they are using brain imaging techniques, such as magnetic resonance imaging (MRI) and electroencephalography (EEG), to peek inside the skull and examine how the brain reacts differently when cognitive tasks are completed by the young and the old, or the healthy and those with injuries.

This article provides a snapshot of Georgia Tech’s research in the biology of the brain.

Developing Better Interventions for Brain Disorders and Injuries

Reducing Epileptic Seizures: Researchers at Georgia Tech and Emory University are investigating the use of electrical stimulation to reduce or eliminate seizures associated with epilepsy, a disorder that affects approximately 2 million people in the United States. Seizures are temporary disturbances in brain function in which groups of nerve cells in the brain fire abnormally and excessively.

To perform their studies, the researchers have created an animal model for temporal lobe epilepsy. Using this model, they can examine different approaches for preventing seizures associated with epilepsy. For one approach, they are implanting tiny electrodes in the animal’s brain that can be used to stimulate neurons and record their activity. The team is also trying to utilize the field of optogenetics – a mix of optical and genetic techniques – to stop the seizures by stimulating the brain with light.

“Our goal is to better understand what causes epileptic seizures and try to find a way to respond to those bursts in activity with stimulation and reduce the number of seizures an individual experiences,” said Steve Potter, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

The stimulation techniques could be a possible alternative for individuals who do not respond to drug therapies and may therefore require surgical resection of the portion of the brain causing the seizures.

Potter is collaborating on this project with Robert Gross, an associate professor in the Departments of Neurosurgery and Neurology at Emory University, and a member of the program faculty in the Coulter Department. Their graduate students, Sharanya Desai and Neal Laxpati, are developing and testing these new brain stimulation therapies in the epileptic rat model. This work has been funded in part by the Wallace H. Coulter Foundation, the National Institutes of Health, Citizens United for Research in Epilepsy (CURE) and the American Epilepsy Society.

Improving Recovery from Spinal Cord Injuries: Following an injury to the brain or spinal cord, a glial scar begins to form. While the scar signifies the beginning of the healing process, neuron extensions – called axons – cannot regenerate through the glial scar, thus preventing repair and recovery.

Ravi Bellamkonda, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, is developing ways to limit the activity of proteins that prevent recovery from spinal cord injuries. (Click image for high-resolution version. Credit: Gary Meek)

The inhibitory characteristics of the scar have been attributed to an increase in proteins known as chondroitin sulfate proteoglycans at the injury site. This family of proteins prevents regeneration of damaged nerve endings.

In a recent study, a research team led by Ravi Bellamkonda, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, examined the influence on central nervous system recovery of a chondroitin sulfate proteoglycan called chondroitin sulfate-4,6 (CS-E). The researchers found that expression of CS-E increased following a central nervous system injury. In cell culture experiments, CS-E inhibited the growth of neurons, and when researchers reduced the amount of CS-E, the inhibition of neuron growth was significantly alleviated.

“Our findings showed that CS-E is a big player in inhibiting nerve growth following an injury, and its expression needs to be reduced as much as possible,” said Bellamkonda.

One strategy to overcome the inhibitory effects of proteins like chondroitin sulfate-4,6 is to enzymatically digest them. In 2009, Bellamkonda developed an improved version of an enzyme capable of digesting chondroitin sulfate proteoglycans.

The researchers eliminated the thermal sensitivity of the enzyme – called chrondroitinase ABC (chABC) – and developed a delivery system that allowed the enzyme to be active for weeks without implanted catheters and pumps. In animal studies, when the thermostabilized enzyme was delivered, the scar at the injury site was significantly degraded for at least six weeks, and enhanced axonal sprouting and recovery of nerve function at the injury site were observed.

“These results brought us a step closer to repairing spinal cord injuries, which require multiple steps including minimizing the extent of secondary injury, bridging the lesion, overcoming inhibition due to scar, and stimulating nerve growth,” said Bellamkonda, who is also the Carol Ann and David D. Flanagan Chair in Biomedical Engineering and a Georgia Cancer Coalition Distinguished Cancer Scholar.

Robert McKeon, an associate professor in cell biology at Emory University, Georgia Tech senior research scientist Lohitash Karumbaiah and graduate student Hyun-Jung Lee also contributed to this work, which was supported by the National Institutes of Health and the Wallace H. Coulter Foundation.

Uncovering the Neural Basis of Rapid Brain Adaptation: Your brain is able to quickly switch from detecting an object flying toward you to determining what the object is through a phenomenon called adaptation.

Garrett Stanley, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, published a study in the journal Nature Neuroscience that detailed the biological basis for rapid adaptation: neurons located at the beginning of the brain’s sensory information pathway that change their level of simultaneous firing. This modification in neuron firing alters the nature of the information being relayed, which enhances the brain’s ability to discriminate between different sensations – at the expense of degrading its ability to detect the sensations themselves.

Associate professor Garrett Stanley (standing) and research scientist Qi Wang, both from the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, are examining how different parts of the brain simultaneously communicate with each other. (Click image for high-resolution version. Credit: Gary Meek)

“Previous studies have focused on how brain adaptation influences how much information from the outside world is being transmitted by the thalamus to the cortex, but we showed that it is also important to focus on what information is being transmitted,” said Stanley.

Recording how neurons in different parts of the brain simultaneously communicate with each other in different situations is a big step in the neuroscience field. The researchers plan to use the techniques from this study to probe the effects of brain injury, which can change the degree of synchronization of neurons in the brain, resulting in harmful effects.

In addition to Stanley, Coulter Department research scientist Qi Wang and Harvard University researchers contributed to this work, which is supported by the National Institutes of Health.

Filling the Neuroscience Toolbox

Device for Probing Neurons in Tissue Samples: Axion BioSystems, a startup company based on intellectual property developed at Georgia Tech, offers neural interfacing technologies for basic science, and for pharmaceutical and clinical research applications. The company has developed microelectrode arrays (MEAs) that allow simultaneous stimulation and recording of neural tissue, and include low-power chips that can  service hundreds of channels.

“Our objective has been to develop devices that can precisely manipulate and monitor electrically active cells and tissues of many types – including brain, spinal, muscle and cardiac – and provide real-time access to complex electrophysiological information,” said James Ross, the company’s chief technical officer. “Researchers using Axion’s technology capture biological models of human heartbeats and brain waves in a dish, which opens the door to a wide range of drug development and safety tests.”

James Ross, chief technical officer of Axion BioSystems, a startup company based on technology devleoped at Georgia Tech, displays the company’s high-throughput Maestro microelectrode array system. (Click image for high-resolution version. Credit: Gary Meek)

In addition to Ross and company CEO Tom O’Brien, Axion BioSystems was founded by School of Electrical and Computer Engineering professor Mark Allen, Department of Biomedical Engineering professor Stephen DeWeerth, research engineer Edgar Brown and Swami Rajaraman, a recent Ph.D. graduate.

Axion has raised more than $9 million from private investors, grants from the National Institutes of Health’s Small Business Innovation Research (SBIR) program and early-stage funding from the Georgia Research Alliance (GRA). The company resides in laboratory and office space at the Advanced Technology Development Center (ATDC) biosciences incubator on Georgia Tech’s campus.

The company is currently working to increase the sales and adoption of its products by pharmaceutical companies, contract research organizations and academic institutions. Since it was founded in 2007, the company has grown from two to 20 employees and launched two commercial products – the Muse and the Maestro.

“The technology we licensed from the Georgia Tech Research Corporation allows us to provide two MEA systems that reduce the cost and complexity of conducting neuroscience research,” explained Ross. “Both systems consist of low-cost, disposable multielectrode arrays, and integrated circuits that eliminate stimulation artifacts and enable simultaneous stimulation and recording.”

The Muse is a bench-top system containing 64 channels for stimulating and recording electroactive tissue. The high-throughput Maestro contains 768 stimulating and recording channels, accommodates multiwell plates of up to 96 wells and is suited for large-scale cellular analysis in commercial drug screening applications.

While the company’s current efforts are focused on pharmaceutical drug screening, ongoing development is expected to result in products in the medical diagnostic and medical device arenas, Ross said.

Devices for Probing Neurons in Living Animals: When high-fidelity recording of individual neurons in live animals is required, whole-cell patch clamp electrophysiology of neurons in vivo is the gold-standard, but it requires great skill to perform. The technique utilizes a glass micropipette to establish electrical and molecular connections to the insides of neurons embedded in intact tissue to record synaptic and ion-channel-mediated events.

MIT researcher Ed Boyden (left) and Georgia Tech researchers Suhasa Kodandaramaiah (seated) and Craig Forest have developed a way to automate the process of finding and recording information from neurons in the living brain. (Click image for high-resolution version. Credit: MIT)

Researchers at Georgia Tech and the Massachusetts Institute of Technology (MIT) have developed a simple robot that automatically performs whole-cell patch clamping in vivo. Using the robot, the researchers have demonstrated high throughput and recording quality in the cortex and hippocampus of small animals.

“With the robot, neuroscientists can achieve high-quality recordings with yields that exceed those of skilled humans at speeds sufficient to enable an unskilled human operator to clamp dozens of cells or more per day and collect data about each one’s gene expression, shape and electrical behavior,” said Craig Forest, an assistant professor in the George W. Woodruff School of Mechanical Engineering.

Applications for the autopatching robot include studying the effects of drugs on neuron electrophysiology; examining neuron behavior in disease states, such as epilepsy and narcolepsy; and classifying neuron cell types on a high-throughput scale.

The robot was designed by Forest; Georgia Tech graduate student Suhasa Kodandaramaiah; Edward Boyden, an associate professor of biological engineering and brain and cognitive sciences at the MIT Media Lab and MIT McGovern Institute; MIT graduate student Giovanni Franzesi; and MIT postdoctoral researcher Brian Chow.

The researchers recently created a startup company, Neuromatic Devices, to commercialize the device. Development of the new technology was funded primarily by the National Institutes of Health, the National Science Foundation and the MIT Media Lab.

Maysam Ghovanloo, an associate professor in Georgia Tech’s School of Electrical and Computer Engineering, has developed a wireless system that collects neural signals from awake, freely moving animals during behavioral neuroscience research experiments. The Wireless Implantable Neural Recording (WINeR) system can simultaneously record from 32 channels for an unlimited period of time using a wireless inductive power transmission system.

School of Electrical and Computer Engineering associate professor Maysam Ghovanloo (right) and graduate student Seung-Bae Lee have developed a wireless system that collects neural signals from awake, freely moving animals during behavioral neuroscience research experiments. (Click image for high-resolution version. Credit: Gary Meek)

“The WINeR system removes the need to tether a small animal via cable to a neural recording device during behavioral neuroscience research experiments and relieves the animal from carrying bulky batteries, thus eliminating two major sources of motion artifacts and bias,” said Ghovanloo.

WINeR is powered by the EnerCage system, which consists of an array of overlapping spiral planar coils that cover the bottom of the experimental area and enable inductive power transmission. A mobile unit attaches to the animal to regulate and deliver a constant amount of inductive power to the WINeR device and any other electrophysiology sensors used to collect data during an experiment, despite animal movements. The mobile unit also contains a small magnet that allows the animal’s location to be tracked in real time.

The researchers plan to add the functionality of wirelessly stimulating neurons to the WINeR device and increase the number of channels it provides.

Ghovanloo is collaborating with Joseph Manns, an assistant professor in the Emory University Department of Psychology, and Karim Oweiss, an associate professor in the Michigan State University Department of Electrical and Computer Engineering and the Neuroscience Program, to test the WINeR and EnerCage systems. This work is supported by the National Science Foundation and the National Institutes of Health.

To alleviate the need for electrodes implanted in the brain, researchers in the Georgia Tech Research Institute (GTRI) are collaborating with Neural Signals Inc. to explore the potential use of near-infrared fluorescent probes to wirelessly transmit neural signals from inside the brain to an external recording device.

A team led by GTRI principal research scientist Brent Wagner is investigating the possibility of connecting neurons to a wireless neural interface system that could respond to low-voltage, low-frequency electrical signals in the brain. The system would consist of a grid of gold nanoparticles, each linked via flexible strand of DNA to a semiconductor quantum dot.

With this system, when a neural cell is at rest, the quantum dot and gold nanoparticle are in close proximity, so no light is emitted from the quantum dot. When a neural cell fires, the voltage change on the neuron’s surface pushes the quantum dot away from the gold nanoparticle, allowing the quantum dot to emit light. The precise location of the quantum dot’s near-infrared luminescence can be detected using an infrared camera.

“The sensing mechanism for the system is based on energy transfer between the quantum dot and the gold nanoparticle,” said Wagner. “We think one of the major advantages of this type of system is its potential to transmit a high throughput of neural signals from multiple recording sites at the same time without the use of bulky cables or implanted electrodes.”

This project is supported by the GTRI Independent Research and Development (IRAD) program.

Researchers in the Georgia Tech School of Chemical and Biomolecular Engineering are building devices to help neuroscientists better understand how neurons in the brain contribute to an organism’s behavior.

Alison Hirsch, a graduate student in the laboratory of Hang Lu, an associate professor in the School of Chemical and Biomolecular Engineering, tests a microfluidic device designed to help neuroscientists better understand how neurons in the brain contribute to an organism’s behavior. (Click image for high-resolution version. Credit: Gary Meek)

Using inexpensive components from ordinary LCD projectors, associate professor Hang Lu can control the brain and muscles of freely moving tiny organisms, including the Caenorhabditis elegans worm that is commonly used for biological studies. Red, green and blue lights from the projector activate light-sensitive microbial proteins that are genetically engineered into the worms, allowing the researchers to switch neurons on and off like light bulbs and turn muscles on and off like engines.

The inexpensive illumination technology allows researchers to stimulate and silence specific neurons and muscles of the worms, while precisely controlling the location, duration, frequency and intensity of the light.

Use of the LCD technology to control small animals advances the field of optogenetics – a mix of optical and genetic techniques that has given researchers unparalleled control over brain circuits in laboratory animals. Until now, the technique could be used only with larger animals by placement of an optical fiber into an animal’s brain, or by illumination of an animal’s entire body.

For another project, Lu developed a microfluidic device that enables genetic studies on small organisms to be performed more quickly. An addition to the system since its original development is a laser beam that can destroy individual neurons. By monitoring the animal’s behavior after the laser ablation, the researchers can infer the function of each neuron. The process takes only 20 to 30 seconds, much less than the half hour it can take to ablate neurons using other techniques.

Lu and collaborators at the Queensland Brain Institute and the University of Queensland in Brisbane, Australia, have also adapted the original design of the microfluidic device to a curved geometry that enables positioning C. elegans bodies into lateral orientations. This alignment makes it easier to analyze neuronal developmental and disease processes that travel from the worm’s head to end or laterally across the worm’s body. Results of this research were published in April 2012 in the journal PLoS ONE.

“These systems have many applications in developmental and behavioral neuroscience of model organisms,” said Lu. “Our challenge is to make them as easy to use as possible so that the technology can make an impact in biological and medical research.”

Lu’s research is supported by the National Science Foundation, the National Institutes of Health and the Alfred P. Sloan Foundation.

Models of How the Brain Processes Information: Christopher Rozell, an assistant professor in the Georgia Tech School of Electrical and Computer Engineering, uses mathematical models and signal processing technologies to understand how the brain organizes and processes images and sounds.

“Machine systems and the human brain perform similar tasks, such as speech recognition and computer vision, but the machines still fall far short of the human brain in these tasks, especially in the areas of power consumption and efficiency,” said Rozell.

In the brain, information about a stimulus in the outside world is communicated to higher centers in the brain by a collection of electrochemical signals present in groups of neurons. Recent evidence indicates that these groups of neurons may represent information by activating only a few of these units – known as a sparse code – and never centralizing the information in a single decision-making unit.

While sparse coding in neural systems is not well understood, Rozell and School of Electrical and Computer Engineering professor Jennifer Hasler and associate professor Justin Romberg are developing neurally plausible analog circuits to quickly find sparse codes. This approach could potentially solve problems relevant for many engineering applications much faster, while using less power than a traditional digital system.

“We don’t have the time or capability to record the characteristics and properties of each of the billions of neurons in the brain to validate our models, but we know our models of neural coding for sensory information are biophysically realistic because we verify them against published results of electrophysiology experiments,” said Rozell.

Researchers in Rozell’s laboratory are also examining what advantages a sparse code might have for the brain, which is making perceptual judgments based on visual data. By investigating how the brain transforms the outside world into meaningful representations it can work with, Rozell hopes better brain-machine interfaces can be designed, more efficient signal processing systems can be developed, and vision and hearing deficits can be corrected. This research is supported by the National Science Foundation and the National Institutes of Health.

Monitoring Activity in the Brain During Cognitive Tasks

Picking Out the Right Tool: Choosing how to use tools to accomplish a task is a natural and seemingly trivial aspect of our lives, yet it can be very difficult for persons with certain brain injuries.

Lewis Wheaton, an assistant professor in the School of Applied Physiology, says access to the Center for Advanced Brain Imaging was a major reason why he joined the faculty at Georgia Tech. (Click image for high-resolution version. Credit: Gary Meek)

“In my laboratory, I study cognitive motor control,” said Georgia Tech School of Applied Physiology assistant professor Lewis Wheaton. “I want to understand the neural system that allows us to select the best tool to accomplish a task, pick that tool up and use it correctly to complete the task without overloading our brains with information.”

In a recent study, Wheaton identified neural activation patterns in the brain associated with watching tools used in correct and incorrect contexts. He used the functional MRI (fMRI) scanner at the Georgia State/Georgia Tech Center for Advanced Brain Imaging, along with electroencephalography (EEG), to record neural activations in the brain as healthy individuals identified whether tools shown in photographs were being used in correct or incorrect contexts. For example, a participant might be shown a hammer and nail, which is a correct tool use, or a hammer and coffee mug – an incorrect tool use.

The fMRI results revealed that when participants identified correct tool use, different parts of the brain became active compared to when they identified incorrect tool use. The EEG recordings provided additional information about the evolution of these activations over time. Activation occurred between 300 and 400 milliseconds after a correct tool use image was shown, but more quickly following onset of an incorrect tool use image. These findings were published in the journals Brain Research and Frontiers in Human Neuroscience.

Wheaton is now using the information he learned about the neural mechanisms of tool use in healthy brains to better understand tool learning and why some individuals experience impaired tool-related behavior following a stroke – a deficit called apraxia.

“In conceptual apraxia, we think the network that codes for incorrect tool use may be selectively damaged and incorrect contextual information is being passed to the areas of the brain activated by correct tool use. Because no error signal arises, contextually inappropriate use becomes possible,” said Wheaton.

Predicting an Individual’s Attentiveness: Shella Keilholz’s long-term research goal is to build a model of spontaneous activity in the brain. As an engineer, she views the brain as a collection of hierarchical networks, with local networks of cells that work together and larger networks where information is transferred between different areas in the brain.

Keilholz is part of a team that is using the fMRI scanner at the Georgia State/Georgia Tech Center for Advanced Brain Imaging to probe the functional connectivity of the brain while an individual is performing a cognitive task requiring vigilance. The researchers are investigating whether the complex neural interactions between spatially distinct brain regions can be used to predict how well an individual will perform on cognitive tasks.

Funding for this work is provided in part by the U.S. Air Force through the Bio-nano-enabled Inorganic/Organic Nanostructures and Improved Cognition (BIONIC) Air Force Center of Excellence at Georgia Tech.

The team’s goal is to find a stable marker in the fMRI signal that is associated with cognitive processing and alertness. Initial results of their experiments show that the level of brain activity preceding the presentation of a visual stimulus can predict how fast an individual will respond to the stimulus during a vigilance task.

“U.S. Air Force analysts must remain attentive to computers and controls for hours at a time, so we are trying to develop a noninvasive way to measure the current state of an individual’s brain and determine if that person is getting off task,” said Keilholz, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “With that information, one might be able to develop a way to refocus that person and get him or her back on task, which would optimize work effectiveness and possibly save lives.”

Also contributing to this project are School of Psychology associate professor Eric Schumacher, and Air Force Research Laboratory biomedical engineer Andrew McKinley and integration manager Lloyd Tripp.

Recalling Memories: Audrey Duarte, an assistant professor in Georgia Tech’s School of Psychology, is a cognitive neuroscientist – someone who looks at the neuroscience that supports human behavior. Duarte’s research is focused on episodic memory, which is the memory of specific events, situations and experiences. Your first day of school, attending a friend’s birthday party and what you ate for dinner last night are examples of episodic memories.

Audrey Duarte, an assistant professor in the School of Psychology, uses the functional MRI scanner at the Georgia State/Georgia Tech Center for Advanced Brain Imaging to measure activity from thousands of neurons in the brain at the same time while subjects try to retrieve episodic memories. (Click image for high-resolution version. Credit: Gary Meek)

Episodic memory can be affected by a number of disorders – including stroke, dementia and Alzheimer’s disease – and even healthy aging. Through her research, Duarte is trying to understand what happens as the brain ages to cause decline in memory abilities over time.

“We want to determine if there are specific areas in the brain or specific brain networks that are disproportionately affected in a negative way by aging, causing lapses in episodic memory,” she said.

Using the fMRI scanner at the Georgia State/Georgia Tech Center for Advanced Brain Imaging, Duarte measures activity from thousands of neurons in the brain at the same time and assesses the patterns of activity while young and older adults examine and subsequently retrieve pictures of common objects from memory. Using this data, Duarte is developing strategies to help older adults better encode and retrieve episodic memories.

“By finding out where an individual’s attention is drawn when looking at a picture, we can better understand the relationship between attention and memory and look for ways to remediate impairments in episodic memory,” said Duarte.

This research is supported by the National Science Foundation, the National Institutes of Health and the American Federation for Aging Research.

Accomplishing Fine Motor Tasks: In another project, Georgia Tech researchers are studying the effects of aging on the neural connectivity between the motor cortex and muscles during tasks that require fine motor skills.

“We know that aging and dual-task paradigms often degrade fine motor performance, so we wanted to compare the performance of young and older adults during the execution of a fine motor task alone and concurrent tasks that required substantial divided attention,” said Minoru Shinohara, an associate professor in the Georgia Tech School of Applied Physiology.

For the study, two groups of healthy adults, one group between the ages of 18 and 38 and the other between 61 and 75, performed tasks involving one-finger motor, two-finger motor, cognitive and concurrent motor-cognitive skills.

As the participants completed the tasks, Shinohara and School of Electrical and Computer Engineering graduate student Ashley Johnson examined the synchrony between two signals – an electroencephalogram (EEG) acquired from the primary motor cortex in the brain and an electromyogram (EMG) acquired from a muscle in the hands. The synchronous measurement is called corticomuscular coherence.

In the study, the older adults demonstrated higher corticomuscular coherence than the young adults during performance of both unilateral and dual tasks. Corticomuscular coherence was highest in the older adults, especially during the dual motor-cognitive task and increased with an additional task for both groups of subjects. But during the motor-cognitive task, corticomuscular coherence was negatively correlated with motor output error across young, but not older, adults. The results of the study were published online in January 2012 in the Journal of Applied Physiology.

“The findings demonstrate that older and younger adults don’t need to use the same neural strategy to accomplish the same motor performance,” said Shinohara. “We are seeing changes in neural strategies for accomplishing fine motor skills with aging.”

In addition to aging, these types of changes in neural strategies could be valuable for rehabilitation applications. Individuals with neurological deficits might benefit from using a different strategy to perform motor tasks, rather than using the same strategy they used before the deficit occurred.

Georgia Tech’s extensive involvement in neuroscience research – from basic to clinical science – reflects the interests of researchers from multiple academic departments and the Georgia Tech Research Institute (GTRI). The researchers are working to better understand how the brain works and apply this knowledge to improving brain function, which has applications for those who have sustained losses due to injuries or disease.

Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke (NS054809, NS079268, NS043486, NS48285, NS062031 and NS058465), the National Institute of Biomedical Imaging and Bioengineering (EB009437 and EB012803), the National Institute on Aging (AG035317 and AG016201), the National Institute of General Medical Sciences (GM088333), the National Eye Institute (EY019965), the National Science Foundation (ECCS-0824199, CBET-0954578, DBI-0649833, CCF-0905346 and BCS-1125683), and the U.S. Air Force (FA9550-09-1-0162). The content is solely the responsibility of the principal investigators and does not necessarily represent the official views of the NIH, NSF or U.S. Air Force.

Research Horizons Magazine
Georgia Institute of Technology
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Media Relations Contact: John Toon (404-894-6986)(jtoon@gatech.edu)

Writer: Abby Robinson

Georgia Tech researcher Jonathan Sylvester examines a group of fishes to look for brooding cichlids. After spawning, females hold their embryos in their mouths, so he looks for fish with closed mouths and protruding lower jaws. (Click image for high-resolution version. Credit: Gary Meek)

Those behavioral differences likely arise from a complex region of the brain known as the telencephalon, which governs communication, emotion, movement and memory in vertebrates – including humans, where a major portion of the telencephalon is known as the cerebral cortex. A study published this week in the journal Nature Communications shows how the strength and timing of competing molecular signals during brain development has generated natural and presumably adaptive differences in the telencephalon much earlier than scientists had previously believed.

In the study, researchers first identified key differences in gene expression between rock- and sand-dweller brains during development, and then used small molecules to manipulate developmental pathways to mimic natural diversity.

“We have shown that the evolutionary changes in the brains of these fishes occur really early in development,” said Todd Streelman, an associate professor in the School of Biology and the Petit Institute for Bioengineering and Biosciences at the Georgia Institute of Technology. “It’s generally been thought that early development of the brain must be strongly buffered against change. Our data suggest that rock-dweller brains differ from sand-dweller brains – before there is a brain.”

Georgia Tech researcher Jonathan Sylvester is shown with a flask containing cichlid embryos. After spawning, female cichlids hold the embryos in their mouths until they are juvenile. The broods can also be grown in flasks to any desired stage of development. (Click image for high-resolution version. Credit: Gary Meek)

For humans, the research could lead scientists to look for subtle changes in brain structures earlier in the development process. This could provide a better understanding of how disorders such as autism and schizophrenia could arise during very early brain development.

The research was supported by the National Science Foundation and published online April 23 by the journal.

“We want to understand how the telencephalon evolves by looking at genetics and developmental pathways in closely-related species from natural populations,” said Jonathan Sylvester, a postdoctoral researcher in the Georgia Tech School of Biology and lead author of the paper. “Adult cichlids have a tremendous amount of variation within the telencephalon, and we investigated the timing and cause of these differences. Unlike many previous studies in laboratory model organisms that focus on large, qualitative effects from knocking out single genes, we demonstrated that brain diversity evolves through quantitative tuning of multiple pathways.”

In examining the fish from embryos to adulthood, the researchers found that the mbuna, or rock-dwellers, tended to exhibit a larger ventral portion of the telencephalon, called the subpallium – while the sand-dwellers tended to have a larger version of the dorsal structure known as the pallium. These structures seem to have evolved differently over time to meet the behavioral and ecological needs of the fishes. The team showed that early variation in the activity of developmental signals expressed as complementary dorsal-ventral gradients, known technically as “Wingless” and “Hedgehog,” are involved in creating those differences during the neural plate stage, as a single sheet of neural tissue folds to form the neural tube.

To specifically manipulate those two pathways, Sylvester removed clutches of between 20 and 40 eggs from brooding female cichlids, which normally incubate fertilized eggs in their mouths. At about 36 to 48 hours after fertilization, groups of eggs were exposed to small-molecule chemicals that either strengthened or weakened the Hedgehog signal, or strengthened or weakened the Wingless signal. The chemical treatment came while the structures that would become the brain were little more than a sheet of cells. After treatment, water containing the chemicals was replaced with fresh water, and the embryos were allowed to continue their development.

A male Cynotilapa afra is shown in a tank in the laboratory of Todd Streelman at Georgia Tech. (Click image for high-resolution version. Credit: Gary Meek)

“We were able to artificially manipulate these pathways in a way that we think evolution might have worked to shift the process of rock-dweller telencephalon development to sand-dweller development, and vice-versa. Treatment with small molecules allows us incredible temporal and dose precision in manipulating natural development,” Sylvester explained. “We then followed the development of the embryos until we were able to measure the anatomical structures – the size of the pallium and subpallium – to see that we had transformed one to the other.”

The two different brain regions, the dorsal pallium and ventral subpallium, give rise to excitatory and inhibitory neurons in the forebrain. Altering the relative sizes of these regions might change the balance between these neuronal types, ultimately producing behavioral changes in the adult fish.

“Evolution has fine-tuned some of these developmental mechanisms to produce diversity,” Streelman said. “In this study, we have figured out which ones.”

The researchers studied six different species of East African cichlids, and also worked with collaborators at King’s College in London to apply similar techniques in the zebrafish.

Georgia Tech researcher Jonathan Sylvester holds a beaker and transfer pipette which are used to collect embryos from brooding female cichlids. (Click image for high-resolution version. Credit: Gary Meek)

As a next step, the researchers would like to follow the embryos through to adulthood to see if the changes seen in embryonic and juvenile brain structures actually do change behavior of adults. It’s possible, said Streelman, that later developmental events could compensate for the early differences.

The results could be of interest to scientists investigating human neurological disorders that result from an imbalance between excitatory and inhibitory neurons. Those disorders include autism and schizophrenia. “We think it is particularly interesting that there may be some adaptive variation in the natural proportions of excitatory versus inhibitory neurons in the species we study, correlated with their natural behavioral differences,” said Streelman.

In addition to the researchers already mentioned, the study included undergraduate coauthors Constance Rich and Chuyong Yi from Georgia Tech, and Joao Peres and Corinne Houart from King’s College in London. Rich is presently in the neuroscience PhD program at the University of Cambridge.

This research was supported by the National Science Foundation (NSF) under grants IOS 0922964 and IOS 1146275. The findings and conclusions are those of the authors and do not necessarily represent the official views of the NSF.

CITATION: Sylvester, J.B., et al., “Competing Signals Drive Telencephalon Diversity,” (Nature Communications, 2013).

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Georgia Tech researcher Wenzhuo Wu holds an array of piezotronic transistors capable of converting mechanical motion directly into electronic controlling signals. The arrays are fabricated on flexible substrates. (Click image for high-resolution version. Credit: Gary Meek)

The arrays include more than 8,000 functioning piezotronic transistors, each of which can independently produce an electronic controlling signal when placed under mechanical strain. These touch-sensitive transistors – dubbed “taxels” – could provide significant improvements in resolution, sensitivity and active/adaptive operations compared to existing techniques for tactile sensing. Their sensitivity is comparable to that of a human fingertip.

The vertically-aligned taxels operate with two-terminal transistors. Instead of a third gate terminal used by conventional transistors to control the flow of current passing through them, taxels control the current with a technique called “strain-gating.” Strain-gating based on the piezotronic effect uses the electrical charges generated at the Schottky contact interface by the piezoelectric effect when the nanowires are placed under strain by the application of mechanical force.

The research was reported April 25 in the journal Science online, at the Science Express website, and will be published in a later version of the print journal. The research has been sponsored by the Defense Advanced Research Projects Agency (DARPA), the National Science Foundation (NSF), the U.S. Air Force (USAF), the U.S. Department of Energy (DOE) and the Knowledge Innovation Program of the Chinese Academy of Sciences.

Georgia Tech researcher Wenzhuo Wu holds an array of piezotronic transistors capable of converting mechanical motion directly into electronic controlling signals. The arrays are fabricated on flexible substrates. (Click image for high-resolution version. Credit: Gary Meek)

“Any mechanical motion, such as the movement of arms or the fingers of a robot, could be translated to control signals,” explained Zhong Lin Wang, a Regents’ professor and Hightower Chair in the School of Materials Science and Engineering at the Georgia Institute of Technology. “This could make artificial skin smarter and more like the human skin. It would allow the skin to feel activity on the surface.”

Mimicking the sense of touch electronically has been challenging, and is now done by measuring changes in resistance prompted by mechanical touch. The devices developed by the Georgia Tech researchers rely on a different physical phenomenon – tiny polarization charges formed when piezoelectric materials such as zinc oxide are moved or placed under strain. In the piezotronic transistors, the piezoelectric charges control the flow of current through the wires just as gate voltages do in conventional three-terminal transistors.

The technique only works in materials that have both piezoelectric and semiconducting properties. These properties are seen in nanowires and thin films created from the wurtzite and zinc blend families of materials, which includes zinc oxide, gallium nitride and cadmium sulfide.

In their laboratory, Wang and his co-authors – postdoctoral fellow Wenzhuo Wu and graduate research assistant Xiaonan Wen – fabricated arrays of 92 by 92 transistors. The researchers used a chemical growth technique at approximately 85 to 90 degrees Celsius, which allowed them to fabricate arrays of strain-gated vertical piezotronic transistors on substrates that are suitable for microelectronics applications. The transistors are made up of bundles of approximately 1,500 individual nanowires, each nanowire between 500 and 600 nanometers in diameter.

In the array devices, the active strain-gated vertical piezotronic transistors are sandwiched between top and bottom electrodes made of indium tin oxide aligned in orthogonal cross-bar configurations. A thin layer of gold is deposited between the top and bottom surfaces of the zinc oxide nanowires and the top and bottom electrodes, forming Schottky contacts. A thin layer of the polymer Parylene is then coated onto the device as a moisture and corrosion barrier.

Images show (A) scanning electron microscopy image and topological profile image of fabricated strain-gated piezotronic transistor array. (B) Optical image of the transparent and flexible SGPT array on flexible substrate. The peripherals are the pads of the device and the central region highlighted by black dashed lines is the active array of SGPTs. (Click image for high-resolution version.)

The array density is 234 pixels per inch, the resolution is better than 100 microns, and the sensors are capable of detecting pressure changes as low as 10 kilopascals – resolution comparable to that of the human skin, Wang said. The Georgia Tech researchers fabricated several hundred of the arrays during a research project that lasted nearly three years.

The arrays are transparent, which could allow them to be used on touch-pads or other devices for fingerprinting. They are also flexible and foldable, expanding the range of potential uses.

Among the potential applications:

• Multidimensional signature recording, in which not only the graphics of the signature would be included, but also the pressure exerted at each location during the creation of the signature, and the speed at which the signature is created.
• Shape-adaptive sensing in which a change in the shape of the device is measured. This would be useful in applications such as artificial/prosthetic skin, smart biomedical treatments and intelligent robotics in which the arrays would sense what was in contact with them.
• Active tactile sensing in which the physiological operations of mechano-receptors of biological entities such as hair follicles or the hairs in the cochlea are emulated.

Because the arrays would be used in real-world applications, the researchers evaluated their durability. The devices still operated after 24 hours immersed in both saline and distilled water.

Future work will include producing the taxel arrays from single nanowires instead of bundles, and integrating the arrays onto CMOS silicon devices. Using single wires could improve the sensitivity of the arrays by at least three orders of magnitude, Wang said.

“This is a fundamentally new technology that allows us to control electronic devices directly using mechanical agitation,” Wang added. “This could be used in a broad range of areas, including robotics, MEMS, human-computer interfaces and other areas that involve mechanical deformation.”

This research was supported by the Defense Advanced Research Projects Agency (DARPA), the National Science Foundation (NSF) under grant CMMI-0946418, the U.S. Air Force (USAF) under grant FA2386-10-1-4070, the U.S. Department of Energy (DOE) Office of Basic Energy Sciences under award DE-FG02-07ER46394 and the Knowledge Innovation Program of the Chinese Academy of Sciences under grant KJCX2-YW-M13. The content is solely the responsibility of the authors and does not necessarily represent the official views of DARPA, the NSF, the USAF or the DOE.

CITATION: Wenzhuo Wu, Xiaonan Wen, Zhong Lin Wang, “Taxel-addressable matrix of vertical-nanowire piezotronic transistors for active/adaptive tactile imaging,” (Science 2013).

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Georgia Tech associate professor Daniel Goldman and researcher Nicole Mazouchova watch FlipperBot move through a bed filled with poppy seeds in the Georgia Tech School of Physics. (Click image for high-resolution version. Credit: Gary Meek)

Both the baby turtles and FlipperBot run into trouble under the same conditions: traversing granular media disturbed by previous steps. Information from the robot research helped scientists understand why some of the hatchlings they studied experienced trouble, creating a unique feedback loop from animal to robot – and back to animal.

The research could help robot designers better understand locomotion on complex surfaces and lead biologists to a clearer picture of how sea turtles and other animals like mudskippers use their flippers. The research could also help explain how animals evolved limbs – including flippers – for walking on land.

The research is scheduled to be published April 24 in the journal Bioinspiration & Biomimetics. The work was supported by the National Science Foundation, the U.S. Army Research Laboratory’s Micro Autonomous Systems and Technology (MAST) Program, the U.S. Army Research Office, and the Burroughs Wellcome Fund.

“We are looking at different ways that robots can move about on sand,” said Daniel Goldman, an associate professor in the School of Physics at the Georgia Institute of Technology. “We wanted to make a systematic study of what makes flippers useful or effective. We’ve learned that the flow of the materials plays a large role in the strategy that can be used by either animals or robots.”

The research began in 2010 with a six-week study of hatchling loggerhead sea turtles emerging at night from nests on Jekyll Island, one of Georgia’s coastal islands. The research was done in collaboration with the Georgia Sea Turtle Center.

Georgia Tech associate professor Daniel Goldman and researcher Nicole Mazouchova pose with FlipperBot, shown in the Georgia Tech School of Physics. Mazouchova was a graduate student in the Georgia Tech School of Biology when the research was done. (Click image for high-resolution version. Credit: Gary Meek)

Nicole Mazouchova, then a graduate student in the Georgia Tech School of Biology, studied the baby turtles using a trackway filled with beach sand and housed in a truck parked near the beach. She recorded kinematic and biomechanical data as the turtles moved in darkness toward an LED light that simulated the moon.

Mazouchova and Goldman studied data from the 25 hatchlings, and were surprised to learn that they managed to maintain their speed regardless of the surface on which they were running.

“On soft sand, the animals move their limbs in such a way that they don’t create a yielding of the material on which they’re walking,” said Goldman. “That means the material doesn’t flow around the limbs and they don’t slip. The surprising thing to us was that the turtles had comparable performance when they were running on hard ground or soft sand.”

The key to maintaining performance seemed to be the ability of the hatchlings to control their wrists, allowing them to change how they used their flippers under different sand conditions.

“On hard ground, their wrists locked in place, and they pivoted about a fixed arm,” Goldman explained. “On soft sand, they put their flippers into the sand and the wrist would bend as they moved forward. We decided to investigate this using a robot model.”

That led to development of FlipperBot, with assistance from Paul Umbanhowar, a research associate professor at Northwestern University. The robot measures about 19 centimeters in length, weighs about 970 grams, and has two flippers driven by servo-motors. Like the turtles, the robot has flexible wrists that allow variations in its movement. To move through a track bed filled with poppy seeds that simulate sand, the robot lifts its flippers up, drops them into the seeds, then moves the flippers backward to propel itself.

Mazouchova, now a Ph.D. student at Temple University, studied many variations of gait and wrist position and found that the free-moving mechanical wrist also provided an advantage to the robot.

“In the robot, the free wrist does provide some advantage,” said Goldman. “For the most part, the wrist confers advantage for moving forward without slipping. The wrist flexibility minimizes material yielding, which disturbs less ground. The flexible wrist also allows both the robot and turtles to maintain a high angle of attack for their bodies, which reduces performance-impeding drag from belly friction.”

A hatchling loggerhead sea turtle makes its way toward the ocean on a beach at Jekyll Island, Ga. Researchers studied the baby turtles — and a robot dubbed “FlipperBot” — to learn about how animals use flippers to move on granular materials like sand. (Click image for high-resolution version. Credit: Nicole Mazouchova)

The researchers also noted that the robot often failed when limbs encountered material that the same limbs had already disturbed. That led them to re-examine the data collected on the hatchling turtles, some of which had also experienced difficulty walking across the soft sand.

“When we saw the turtles moving poorly, they appeared to be suffering from the same failure mode that we saw in the robot,” Goldman explained. “When they interacted with materials that had been previously disturbed, they tended to lose performance.”

Mazouchova and Goldman then worked with Umbanhowar to model the robot’s performance in an effort to predict how the turtle hatchlings should respond to different conditions. The predictions closely matched what was actually observed, closing the loop between robot and animal.

“The robot study allowed us to test how principles applied to the animals,” Goldman said.

While the results may not directly improve robot designs, what the researchers learned should contribute to a better understanding of the principles governing movement using flippers. That would be useful to the designers of robots that must swim through water and walk on land.

“A multi-modal robot might need to use paddles for swimming in water, but it might also need to walk in an effective way on the beach,” Goldman said. “This work can provide fundamental information on what makes flippers good or bad. This information could give robot designers clues to appendage designs and control techniques for robots moving in these environments.”

FlipperBot moves through a bed filled with poppy seeds in the Georgia Tech School of Physics. The research, which also included a study of sea turtle hatchlings, provides new information on the principles governing locomotion on granular surfaces. (Click image for high-resolution version. Credit: Gary Meek)

The research could ultimately provide clues to how turtles evolved to walk on land with appendages designed for swimming.

“To understand the mechanics of how the first terrestrial animals moved, you have to understand how their flipper-like limbs interacted with complex, yielding substrates like mud flats,” said Goldman. “We don’t have solid results on the evolutionary questions yet, but this certainly points to a way that we could address these issues.”

This research has been supported by the National Science Foundation under grant CMMI-0825480 and the Physics of Living Systems PoLS program, the U.S. Army Research Laboratory’s (ARL) Micro Autonomous Systems and Technology (MAST) Program under cooperative agreement W911NF-08-2-0004, the U.S. Army Research Office (ARO) and the Burroughs Wellcome Fund Career Award. Any conclusions are those of the authors and do not necessarily represent the official views of the NSF, ARL or ARO.

CITATION: Nicole Mazouchova, Paul B. Umbanhowar and Daniel I. Goldman, “Flipper-driven terrestrial locomotion of a sea turtle-inspired robot, (Bioinspiration & Biomimetics, 2013).

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Douglas Woods, a Georgia Tech Research Institute (GTRI) research scientist and IBESS program manager, poses with a mannequin equipped with the Integrated Blast Effect Sensor Suite system. (Click image for high-resolution version. Credit: Gary Meek)

In 2011, the Army’s Rapid Equipping Force (REF) approached the Georgia Tech Research Institute (GTRI) as part of the Department of Defense Information Analysis Program (IAC) to develop a system that measures the physical environment of an explosion and collects data that can be used to correlate what the soldier experienced with long-term medical outcomes, especially traumatic brain injury.

The solution: the Integrated Blast Effect Sensor Suite (IBESS). IBESS is the first system to acquire integrated, time-tagged data during an explosive event – whether soldiers are on the ground or riding in a vehicle – and can later help recreate a holistic picture of what happened.

System of systems

There are two parts to a blast: a shock wave that travels at supersonic speed, and compressed air, which travels in front of the shock wave. Both can cause considerable damage to the human body, but the exact effects are unclear.

“No one knows to what extent overpressure or acceleration causes injuries,” said Marty Broadwell, a principal research scientist at GTRI who manages the institute’s projects with REF. “Nor do we know how quickly an injury will show up, how long it will last or which soldiers are more resistant to harm than others. The only way to understand the impact of a blast is to collect data, which is precisely what IBESS does.”

How it works

IBESS features two major subsystems: a unit worn by the soldier and a vehicle sensor suite. The soldier system is contained in a canvas pouch, which attaches to a soldier’s armor between his or her shoulder blades. A recorder in the pouch connects to four pressure sensors, two on the back and two on straps that hang over the front of the shoulders. Because these sensors face different quadrants, the unit captures directionality and more information than previous blast gauges.

Components of the Integrated Blast Effect Sensor Suite (IBESS) are shown. The system measures the physical environment of an explosion and collects data that can be used to correlate what the soldier experienced with long-term medical outcomes. (Click image for high-resolution version. Credit: Gary Meek)

“Soldiers already carry considerable gear, so reducing the weight of the body unit and power consumption of its batteries drove many design decisions,” said Brian Liu, a GTRI research engineer who served as technical lead on the project. For example, the recorder in the soldier body unit remains in sleep mode until pressure or shock waves hit a certain threshold, causing it to wake and begin recording data.  This allows the system to have longer battery life and remain relatively transparent to the wearer.

The vehicle system serves a dual purpose: It records blast events that affect the vehicle, but also interacts and automatically links with the soldier system. When a soldier enters a vehicle, a base station installed in seats transmits RFID signals. If the soldier system has stored any data, these signals initiate a Bluetooth connection that enables two-way communication and data transfer. This semi-passive RFID technology is proximity based; transmission and reception occur only at very close range, so IBESS can identify a soldier’s precise location in the vehicle.

Sensors are also installed on the vehicle’s interior frame and seats. If an explosion or rollover occurs, these sensors collect linear acceleration and angular rotation data. The soldier system also wakes up and begins to record and transmit data. A single board computer aggregates data from both the vehicle and soldier systems and then passes it on to a rugged black box for final storage.

IBESS is specifically designed to withstand tremendous forces of an IED explosion.

“Materials, mounting strategies and mechanical isolation strategies have been used to ensure the devices successfully capture data in ‘survivable’ events,” Liu explained. “We first conducted research on what kinds of magnitudes of blasts were survivable for mounted and dismounted operations and then performed many tests at those levels for verification.”

IBESS is innovative on many fronts:

• Synchronized data: Unlike earlier generations of blast gauges, all data in IBESS is time-tagged, using GPS time as common time source. “Using this data we can rebuild an event,” Liu explained. “Even though soldiers aren’t wired together, we’ll know they were in the same vehicle and experienced the same event — and can assess how an event propagated through.”
• Scalability: GTRI researchers used as many off-the-shelf and standard components as possible. “This open architecture makes it easier to expand the system,” observed Douglas Woods, GTRI research scientist and IBESS program manager.
• Anonymity: By leveraging the Department of Defense’s Common Access Card (CAC) system’s Personal Key Identifier (PKI), IBESS can collect information uniquely tied to individual soldiers. Use of the PKI makes the data virtually anonymous so other researchers can study it without compromising privacy or containing personally identifiable information.

Douglas Woods, Georgia Tech Research Institute (GTRI) research scientist and IBESS program manager, poses with a mannequin equipped with the Integrated Blast Effect Sensor Suite system. (Click image for high-resolution version. Credit: Gary Meek)

Another hallmark of the project was its rapid completion schedule. REF awarded the contract to GTRI in July 2011. Researchers wrapped up preliminary designs in September, and by early 2012 they were testing and refining the system. IBESS units began to ship overseas in August, and now the system has been issued to more than 650 troops and will be installed on 42 vehicles in Afghanistan.

“Our work with GTRI has been outstanding,” said Joe Rozmeski, REF’s deputy chief of technology management. “Originally chosen for its sensor expertise, GTRI has proven to be an ideal partner for us. They understand their role perfectly and are in tune with the REF’s objectives for integrated blast effect research and collection.”

Understanding the challenge

At its peak, the project involved more than 50 researchers with expertise ranging from electronics to mechanical engineering to health systems. This diversity in disciplines was critical to IBESS’ success.

“If you don’t understand the context in which a device will be used, you won’t be collecting the right information, said Shean Phelps, M.D., a principal research scientist who joined GTRI in 2011. A retired Army officer, Phelps was a Special Forces (Green Beret) weapons, medic and team sergeant before becoming a physician and was instrumental not only in initiating the IBESS project but also in providing both operational and medical perspectives.

Traumatic brain injury has become a greater concern in recent years. “Because of improved equipment and medical services, people are surviving severe explosions,” Phelps explained. “Yet we lack a clear understanding of blast-induced injuries on the human nervous system. Mild traumatic brain injury is a particular concern because it has a wide range of symptoms and doesn’t show up reliably in tests, so we can’t effectively diagnose, treat and manage its long-term effects.”

With IBESS, complex contextual data can be collected to link soldiers’ experiences with their medical records and later correlate a blast event to traumatic brain injury. IBESS is a major step forward for both the medical and engineering communities, Phelps said: “We now have a platform that’s dramatically different from previous efforts to collect blast data because it’s time-tagged, fully integrated between humans and vehicles, able to pinpoint an individual’s location in a vehicle — and able to accept data from any sensor.”

What’s ahead

Ongoing work is being conducted by a team of GTRI research engineers led by Allesio Medda, who are building a structured database and analytical tools for the data that IBESS collects. Other GTRI researchers are installing sensors in the ear-cup of communications headsets worn by soldiers, which measure linear and rotational acceleration on six axes. After testing, these headsets will be issued to 200 Army Rangers.

Currently IBESS only captures environmental data. Yet because of its open architecture, other diagnostic capabilities can be easily integrated. For example, sensors could be added to monitor heart rate, blood pressure, oxygen and hydration levels, body temperature and EKG activity.

With such biometric sensors, IBESS could evaluate soldiers’ physical condition in training or on the battlefield for triage purposes or to assess their ability to do a certain job. Data from the system could be used to improve equipment and vehicle design. For example, gear might be developed to divert a shock wave or change its frequency if a particular frequency is shown to damage the brain. IBESS could also be adapted for non-military applications, such as monitoring construction workers, race car drivers or elderly people in their homes.

“Collecting physical data on the blast environment is the critical first step before the system can be made medically predictive,” stressed Woods. “An explosion is a physical phenomenon. In order to understand the extent of injuries and how to prevent them, you must first understand the physics.”

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Assistant professor Yang Wang from Georgia Tech’s School of Civil and Environmental Engineering displays a strain-testing specimen mounted with a wireless antenna sensor. (Click image for high-resolution version. Credit: Gary Meek)

Researchers at the Georgia Institute of Technology are developing a novel technology that would facilitate close monitoring of structures for strain, stress and early formation of cracks. Their approach uses wireless sensors that are low cost, require no power, can be implemented on tough yet flexible polymer substrates, and can identify structural problems at a very early stage. The only electronic component in the sensor is an inexpensive radio-frequency identification (RFID) chip.

Moreover, these sensor designs can be inkjet-printed on various substrates, using methods that optimize them for operation at radio frequency. The result would be low-cost, weather-resistant devices that could be affixed by the thousands to various kinds of structures.

“For many engineering structures, one of the most dangerous problems is the initiation of stress concentration and cracking, which is caused by overloading or inadequate design and can lead to collapse – as in the case of the I-35W bridge failure in Minneapolis in 2007,” said Yang Wang, an assistant professor in the Georgia Tech School of Civil and Environmental Engineering. “Placing a ‘smart skin’ of sensors on structural members, especially on certain high-stress hot spots that have been pinpointed by structural analysis, could provide early notification of potential trouble.”

Close-up photo of a crack-testing specimen mounted with a wireless antenna sensor. The device could be used to provide close monitoring of bridges, parking decks and other structures for early signs of strain, stress and formation of cracks. (Click image for high-resolution version. Credit: Gary Meek)

Wang is collaborating with a team that includes professor Manos M. Tentzeris of the School of Electrical and Computer Engineering, and Roberto Leon, a former Georgia Tech professor who recently moved to Virginia Tech. The work is supported by the Federal Highway Administration.

This research was recently reported in IEEE Antennas and Wireless Propagation Letters, Volume 11, 2012, and International Journal of Smart and Nano Materials, Volume 2, 2011. Parts of this research were also presented at ASME 2012 Conference on Smart Materials, Adaptive Structures and Intelligent Systems (SMASIS) and several other conferences.

Antennas as Sensors

The Georgia Tech research team is focusing on wireless sensor designs that are passive, which means they need no power source. Instead, these devices respond to radio-frequency signals sent from a central reader or hub. One such reader can interrogate multiple sensors, querying them on their status at frequent intervals.

The researchers’ approach utilizes a small antenna mounted on a substrate and tuned to a specific radio frequency. This technique enables the antenna itself to function as a stress sensor.

Graduate research assistants Xiaohua Yi and Chunhee Cho and assistant professor Yang Wang (shown left-to-right) of the Georgia Tech School of Civil and Environmental Engineering inspect strain- and crack-testing specimens used in research on wireless antenna sensors. (Click image for high-resolution version. Credit: Gary Meek)

As long as the structural member to which the antenna/sensor is affixed remains entirely stable, its frequency stays the same. But even a slight deformation in the structure also deforms the antenna and alters its frequency response. The reader can detect that change at once, initiating a warning months or years before an actual collapse.

“A key benefit of this technology is that it’s completely wireless,” Wang said. “It doesn’t require a battery, and you don’t have to climb around on bridges running long connecting cables.”

The research team has developed a prototype strain/crack sensor that has been successfully tested in the laboratory, Wang said. The simple device consists of a small piece of copper mounted on a polymer substrate, plus a 10-cent 1mm by 1mm RFID chip. The chip is used to distinguish each individual sensing unit from others. The simple sensor architecture allows it to be made at very low cost and to potentially be deployed in large quantities on any bridge.

Inkjet-Printed Circuits

More sophisticated designs are in the works. Tentzeris’ team is tackling an approach that produces strain sensors using different applications of inkjet printing technology.

Assistant professor Yang Wang from Georgia Tech’s School of Civil and Environmental Engineering displays a crack-testing specimen mounted with a wireless antenna sensor. (Click image for high-resolution version. Credit: Gary Meek)

One such design uses a silver-nanoparticle-based ink that is applied to a flexible or semi-flexible substrate, said Rushi Vyas, a Ph.D. student working with Tentzeris. The ink lays down a structure that can change properties in response to strain.

A second approach involves the use of inkjet-printed carbon-nanotube-based structures, Vyas said. In this case, the nanotubes themselves produce an altered response when subjected to deformation.

In laboratory testing, the team’s prototype sensors have demonstrated high sensitivity in response to even slight changes in metal structures, Wang said. The sensors have been able to reliably detect a degree of deformation change as low as tens of microstrains (one microstrain equals 0.0001 percent, or 1 part per million), and they can continuously monitor stress accumulation until the metal develops a severe crack.

One issue still being addressed is the capacity of the passive sensor to respond to a reader. A reader transmits a radio-frequency beam to a sensor, which utilizes that received energy to reflect a signal back to the reader.

But this technique can be rather inefficient, Vyas said. A signal from a reader might travel 50 feet, yet the sensor’s response might only travel back 10 feet. One issue is that readers are limited by FCC regulations, which govern how much power can be transmitted to the sensor.

Increasing the Power

What’s needed are ways to supply a sensor with a power source that would increase the range of the response signal. Batteries are not preferred because they can be undependable and require periodic replacement.

Close-up photo of a strain-testing specimen mounted with a wireless antenna sensor. The device could be used to provide close monitoring of bridges, parking decks and other structures for early signs of strain, stress and formation of cracks. (Click image for high-resolution version. Credit: Gary Meek)

One candidate solution – in addition to solar-energy and vibration-energy harvesting – is scavenged energy, Tentzeris said. A Georgia Tech team that includes Tentzeris and Vyas is researching ways to gather power from ambient or electromagnetic energy in the air, such as television, radio, radar or other manmade signals found in Earth’s lower atmosphere.

Scavenging experiments utilizing TV bands have already yielded power amounting to hundreds of microwatts. Multi-band systems are expected to generate one milliwatt or more – enough to operate some small electronic devices such as low-power wireless sensors.

Tentzeris noted that smart-skin technology may soon help to enable a broad range of applications. These could include not only real-time stress monitoring in bridges, factories and buildings, but also new and extremely lightweight aircraft with self-sensing/self-diagnostic capabilities, and battery-free methods for monitoring structures after major disasters such as earthquakes or hurricanes.

“The wireless strain sensor could prove to be an effective, low-cost and easy-to-scale solution to a very important need,” Tentzeris said. “A simple device – consisting of an antenna, an inexpensive RFID chip and some power-boosting technology – could quietly monitor at-risk structures for many years, and then send back a real-time warning if there’s suddenly a problem.”

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Media Relations Contact: John Toon (404-894-6986)(jtoon@gatech.edu).

Writer: Rick Robinson

A team of Georgia Tech researchers adjusts equipment used to study a gaseous Bose-Einstein condensate composed of sodium atoms. The condensate could be used for communicating among quantum computers. Shown, (l-r) are postdoctoral fellow Carlo Samson, associate professor Chandra Raman and graduate student Anshuman Vinit. (Click image for high-resolution version. Credit: Gary Meek)

One proposed solution is to divide the computing among multiple small quantum computers that would work together much as today’s multi-core supercomputers team up to tackle big digital operations. The individual computers in such a system could communicate quantum information using Bose-Einstein condensates (BECs) – clouds of ultra-cold atoms that all exist in exactly the same quantum state. The approach could address the decoherence problem by reducing the number of bits necessary for a single computer.

Now, a team of physicists at the Georgia Institute of Technology has examined how this Bose-Einstein communication might work. The researchers determined the amount of time needed for quantum information to propagate across their BEC, essentially establishing the top speed at which such quantum computers could communicate.

“What we did in this study was look at how this kind of quantum information would propagate,” said Chandra Raman, an associate professor in Georgia Tech’s School of Physics. “We are interested in the dynamics of this quantum information flow not just for quantum information systems, but also more generally for fundamental problems in physics.”

Georgia Tech associate professor Chandra Raman adjusts equipment used to study a gaseous Bose-Einstein condensate composed of sodium atoms. The condensate could be used for communicating among quantum computers. (Click image for high-resolution version. Credit: Gary Meek)

The research is scheduled to be published in the April 19 online version of the journal Physical Review Letters. The research was funded by the U.S. Department of Energy (DOE) and the National Science Foundation (NSF). The work involved both an experimental physics group headed by Raman and a theoretical physics group headed by associate professor Carlos Sa De Melo, also in the Georgia Tech School of Physics.

The researchers first assembled a gaseous Bose-Einstein condensate that consisted of as many as three million sodium atoms cooled to nearly absolute zero. To begin the experiment, they switched on a magnetic field applied to the BEC that instantly placed the system out of equilibrium. That triggered spin-exchange collisions as the atoms attempted to transition from one ground state to a new one. Atoms near one another became entangled, pairing up with one atom’s spin pointing up, and the other’s pointing down. This pairing of opposite spins created a correlation between pairs of atoms that moved through the entire BEC as it established a new equilibrium.

The researchers, who included graduate student Anshuman Vinit and former postdoctoral fellow Eva Bookjans, measured the correlations as they spread through the cloud of cold atoms. At first, the quantum entanglement was concentrated in space, but over time, it spread outward like drop of dye diffuses through water.

“You can imagine having a drop of dye that is concentrated at one point in space,” Raman said. “Through diffusion, the dye molecules move throughout the water, slowly spreading throughout the entire system.”

The research could help scientists anticipate the operating speed for a quantum computing system composed of many cores communicating through a BEC.

“This propagation takes place on the time scale of ten to a hundred milliseconds,” Raman said. “This is the speed at which quantum information naturally flows through this kind of system. If you were to use this medium for quantum communication, that would be its natural time scale, and that would set the timing for other processes.”

These images show that quantum correlations in the Georgia Tech Bose-Einstein condensate are highly concentrated at first (top graph), then slowly diffuse outward (lower two graphs). The peaks show the localization of the correlations. (Click image for high-resolution version. Image courtesy of Chandra Raman)

Though relevant to communication of quantum information, the process also showed how a large system undergoing a phase transition does so in localized patches that expand to attempt to incorporate the entire system.

“An extended system doesn’t move from one phase to another in a uniform way,” said Raman. “It does this locally. Things happen locally that are not connected to one another initially, so you see this inhomogeneity.”

Beyond quantum computing, the results may also have implications for quantum sensing – and for the study of other physical systems that undergo phase transitions.

“Phase transitions have universal properties,” Raman noted. “You can take the phase transitions that happen in a variety of systems and find that they are described by the same physics. It is a unifying principle.”

Raman hopes the work will lead to new ways of thinking about quantum computing, regardless of its immediate practical use.

“One paradigm of quantum computing is to build a linear chain of as many trapped ions as possible and to simultaneously engineer away as many challenges as possible,” he said. “But perhaps what may be successful is to build these smaller quantum systems that can communicate with one another. It’s important to try as many things as possible and to keep an open mind. We need to try to understand these systems as well as we can.”

This research was supported by the Department of Energy (DOE) through grant DE-FG-02-03ER15450 and by the National Science Foundation under grant PHY-1100179. The conclusions in this article are those of the principal investigator and do not necessarily represent the official views of the DOE or the NSF.

CITATION: Vinit, Anshuman, et al., “Antiferromagnetic Spatial Ordering in a Quenched One-dimensional Spinor Gas, (Physical Review Letters, 2013).

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Georgia Tech Research Institute (GTRI) researchers are using a Diamond DA-40 aircraft to simulate sensors that may be present on enemy UAVs. The technology – produced by GTRI as part of its Threat Unmanned Devices Program – is expected to be used to gauge the effectiveness of U.S. countermeasures against enemy drones. (Click image for high-resolution version. Credit: GTRI)

As part of its broad-based work in electronic warfare technologies, the Georgia Tech Research Institute (GTRI) is developing integrated hardware devices that simulate sensors potentially present on enemy UAVs. The technology – produced by GTRI as part of its Threat Unmanned Devices Program – is expected to be used to gauge the effectiveness of U.S. countermeasures against enemy drones. The research is sponsored by the U.S. Army Threat Systems Management Office.

“The assets that we’re building can simulate the threat capability you would expect on a foreign unmanned aerial vehicle,” said Vince Camp, a GTRI senior research engineer who is a principal investigator for the project. “We’re reproducing the ISR [intelligence, surveillance and reconnaissance] capability that a threat UAV would have. Simulating this ISR capability makes it possible to test the effectiveness of U.S. countermeasures against a potentially hostile signal intelligence capability in the air.”

When aloft, GTRI’s integrated devices simulate three principal threat capabilities, said Doug Martin, a senior research engineer who directs the GTRI Threat Unmanned Devices Program. The simulated threats include an electro-optical infrared sensor package that includes thermal-imaging capability, other sensors that detect and analyze U.S. communication signals, and equipment capable of jamming U.S. weapons systems. Additional threat-simulation capabilities could be added in the future.

“The intent here isn’t to shoot down a hostile UAV or even to prevent it from being there,” Martin explained. “We want to know what information that vehicle is trying to gather, and what can be done to minimize the exposure of that information.”

Currently, he noted, GTRI’s threat simulator payload is being used on a Diamond DA-40 manned aircraft rather than a UAV. That’s largely because the presence of a human pilot makes it easier to obtain clearance to fly over U.S. ground forces and ground assets at test ranges. Acquiring clearance for a UAV flyover is more difficult and time-consuming due to safety concerns.

After takeoff, the test aircraft is directed entirely by a ground operator. The human pilot simply executes the flight plan and commands sent from the ground, maintaining a human-in-the-loop in the event of an emergency.

The simulator devices are controlled from the ground via a FalconView interface, which also provides the pilot direction. FalconView is a widely used mapping system created by GTRI that displays maps and other information useful to military mission planners, aviators and aviation support personnel.

“From the standpoint of the ground operator, the manned aircraft will look and function like a UAV,” Martin said. “The ground control interface makes it look like it’s an autonomous vehicle up there.”

The GTRI team has finished integration of the threat-simulation devices that are called for under current plans and has passed initial acceptance tests in the air. The completed system was demonstrated successfully at a missile range in fall 2012.

Eventually, Camp said, it’s possible that GTRI’s threat simulator hardware will be placed on true UAVs, which could be either ground-controlled or fully autonomous. Mounting a simulation payload on a UAV could provide a more complete, multi-function test environment.

“Currently, simulating threat UAV payload performance is the priority over simulating the signature of the aircraft,” Camp said. “In the future, a test UAV platform could provide a more realistic radar cross-section, electro-optic/infrared signature and acoustic signature needed to provide a complete threat UAV test capability. What we learn from testing with the UAV threat simulator will help us deploy countermeasures more effectively.”

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Transmission electron microscope (TEM) images show four distinctive types of nanocrystals that were obtained at different reaction temperatures during experiments to study the effects of surface diffusion. (Click image for high-resolution version. Image courtesy of Younan Xia)

Using systematic experiments, researchers have investigated how surface diffusion – a process in which atoms move from one site to another on nanoscale surfaces – affects the final shape of the particles. The issue is important for a wide range of applications that use specific shapes to optimize the activity and selectivity of nanoparticles, including catalytic converters, fuel cell technology, chemical catalysis and plasmonics.

Results of the research could lead to a better understanding of how to manage the diffusion process by controlling the reaction temperature and deposition rate, or by introducing structural barriers designed to hinder the surface movement of atoms.

“We want to be able to design the synthesis to produce nanoparticles with the exact shape we want for each specific application,” said Younan Xia, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “Fundamentally, it is important to understand how these shapes are formed, to visualize how this happens on structures over a length scale of about 100 atoms.”

The research was reported April 8 in the early online edition of the journal Proceedings of the National Academy of Sciences (PNAS). The research was sponsored by the National Science Foundation (NSF).

Controlling the shape of nanoparticles is important in catalysis and other applications that require the use of expensive noble metals such as platinum and palladium. For example, optimizing the shape of platinum nanoparticles can substantially enhance their catalytic activity, reducing demand for the precious material, noted Xia, who is a Georgia Research Alliance (GRA) eminent scholar in nanomedicine. Xia also holds joint appointments in the School of Chemistry and Biochemistry and the School of Chemical and Biomolecular Engineering at Georgia Tech.

“Controlling the shape is very important to tuning the activity of catalysts and in minimizing the loading of the catalysts,” he said. “Shape control is also very important in plasmonic applications, where the shape controls where optical absorption and scattering peaks are positioned. Shape is also important to determining where the electrical charges will be concentrated on nanoparticles.”

Though the importance of particle shape at the nanoscale has been well known, researchers hadn’t before understood the importance of surface diffusion in creating the final particle shape. Adding atoms to the corners of platinum cubes, for instance, can create particles with protruding “arms” that increase the catalytic activity. Convex surfaces on cubic particles may also provide better performance. But those advantageous shapes must be created and maintained.

Natural energetic preferences related to the arrangement of atoms on the tiny structures favor a spherical shape that is not ideal for most catalysts, fuel cells and other applications.

In their research, Xia and his collaborators varied the temperature of the process used to deposit atoms onto metallic nanocrystals that acted as seeds for the nanoparticles. They also varied the rates at which atoms were deposited onto the surfaces, which were determined by the injection rate at which a chemical precursor material was introduced. The diffusion rate is determined by the temperature, with higher temperatures allowing the atoms to move around faster on the nanoparticle surfaces. In the research, bromide ions were used to limit the movement of the added atoms from one portion of the particle to another.

Using transmission electron microscopy, the researchers observed the structures that were formed under different conditions. Ultimately, they found that the ratio of the deposition rate to the diffusion rate determines the final shape. When the ratio is greater than one, the adsorbed atoms tend to stay where they are placed. If the ratio is less than one, they tend to move.

“Unless the atomic reaction is at absolute zero, you will always have some diffusion,” said Xia, who holds the Brock Family Chair in the Department of Biomedical Engineering. “But if you can add atoms to the surface in the places that you want them faster than they can diffuse, you can control the final destination for the atoms.”

Xia believes the research may also lead to improved techniques for preserving the unique shapes of nanoparticles even at high operating temperatures.

“Fundamentally, it is very useful for people to know how these shapes are formed,” he said. “Most of these structures had been observed before, but people did not understand why they formed under certain conditions. To do that, we need to be able to visualize what happens on these tiny structures.”

Xia’s research team also studied the impact of diffusion on bi-metallic particles composed of both palladium and platinum. The combination can enhance certain properties, and because palladium is currently less expensive than platinum, using a core of palladium covered by a thin layer of platinum provides the catalytic activity of platinum while reducing cost.

In that instance, surface diffusion can be helpful in covering the palladium surface with a single monolayer of the platinum. Only the surface platinum atoms will be able to provide the catalytic properties, while the palladium core only serves as a support.

The research is part of a long-term study of catalytic nanoparticles being conducted by Xia’s research group. Other aspects of the team’s work addresses biomedical uses of nanoparticles in such areas as cancer therapy.

“We are very excited by this result because it is generic and can apply to understand and control diffusion on the surfaces of many systems,” Xia added. “Ultimately we want to see how we can take advantage of this diffusion to improve the catalytic and optical properties of these nanoparticles.”

The research team also included Xiaohu Xia, Shuifen Xie, Maochang Liu and Hsin-Chieh Peng at Georgia Tech; and Ning Lu, Jinguo Wang and Professor Moon J. Kim at the University of Texas at Dallas.

This research was supported by the National Science Foundation (NSF) under grant DMR-1215034 and by startup funds from Georgia Tech. Any conclusions expressed are those of the principal investigator and may not necessarily represent the official views of the NSF.

CITATION: Xia, Xiaohu, et al., “On the role of surface diffusion in determining the shape or morphology of noble-metal nanocrystals,” (Proceedings of the National Academy of Science, 2013). http://www.pnas.org/content/early/2013/04/05/1222109110

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