Caltech Research Helps Paraplegic Man Stand and Move Legs Voluntarily

PASADENA, Calif.—A team of researchers from the University of California, Los Angeles (UCLA), the California Institute of Technology (Caltech), and the University of Louisville have used a stimulating electrode array to assist a paralyzed man to stand, step on a treadmill with assistance, and, over time, to regain voluntary movements of his limbs. The electrical signals provided by the array, the researchers have found, stimulate the spinal cord's own neural network so that it can use the sensory input derived from the legs to direct muscle and joint movements.

Rather than bypassing the man's nervous system to directly stimulate the leg muscles, this approach takes advantage of the inherent control circuitry in the lower spinal cord (below the level of the injury) to control standing and stepping motions.

The study is published today in the British medical journal The Lancet.

More than 5.6 million Americans live with some form of paralysis; of these, 1.3 million have had spinal-cord injuries, often resulting in complete paralysis of the lower extremities, along with loss of bladder and bowel control, sexual response, and other autonomous functions.

The work originated with a series of animal experiments beginning in the 1980s by study coauthors V. Reggie Edgerton and Yury Gerasimenko of the David Geffen School of Medicine at UCLA that ultimately showed that animals with spinal-cord injuries could stand, balance, bear weight, and take coordinated steps while being stimulated epidurally—that is, in the space above the dura, the outermost of the three membranes that cover the brain and spinal cord.

Starting eight years ago, Joel Burdick, a professor of mechanical engineering and bioengineering at Caltech, teamed with the Edgerton lab to study how robotically guided physical therapy and pharmacology could be coupled to better recover locomotion in animals with spinal-cord injuries.

Building upon these studies and the earlier work of Edgerton and Gerasimenko, Burdick and Yu-Chong Tai, a Caltech professor of electrical engineering and mechanical engineering, introduced the concept of high-density epidural spinal stimulation, which uses sheet-like arrays of numerous electrodes to stimulate neurons. The goal of the system, Burdick says, "is to stimulate the native standing and stepping control circuitry in the lower spinal cord so as to coordinate sensory-motor activity and partially replace the missing signals from above"—that is, from the brain—"and shout 'get going!' to the nerves."

Electrical leads implanted in the paraplegic patient.
Credit: Medtronic, Inc.

To test this concept, which was first explored in animal models, the team used a commercially available electrode array, which is normally used to treat back pain. While this commercial array does not have all of the capabilities of the arrays tested so far in animals, it allowed the team to test the viability of high-density epidural stimulation in humans. The results, Burdick says, "far exceeded" the researchers' expectations.

The subject in the new work is a 25-year-old former athlete who was completely paralyzed below the chest in a hit-and-run accident in July 2006. He suffered a complete motor injury at the C7/T1 level of the spinal cord, but retained some sensation in his legs.

Before being implanted with the epidural stimulating array, the patient underwent 170 locomotor training sessions over a period of more than two years at the Frazier Rehab Institute. In locomotor training, a rehabilitative technique used on partially paralyzed patients, the body of the patient is suspended in a harness over a moving treadmill while trained therapists repeatedly help manipulate the legs in a repetitive stepping motion.

The training had essentially no effect on this patient, confirming the severity of his spinal injury.  The training also established a "baseline" against which the subsequent efficacy of the electrical stimulation could be measured.

After implantation with the device, however, the patient could—while receiving electrical stimulation, and after a few weeks of locomotor training—push himself into a standing position and bear weight on his own. He can now remain standing, and bearing weight, for 20 minutes at a time. With the aid of a harness support and some therapist assistance, he can make repeated stepping motions on a treadmill.  With repeated daily training and electrical stimulation, the patient regained the ability to voluntarily move his toes, ankles, knees, and hips on command.

The patient has no voluntary control over his limbs when the stimulation is turned off.

In addition, over time he experienced improvements in several types of autonomic function, such as bladder and bowel control, as well as temperature regulation—a "surprise" outcome, Burdick says, that, if replicated in further studies, could substantially improve the lives of patients with spinal-cord injuries.

Credit: The Lancet

These autonomic functions began to return before there was any sign of voluntary movement, which was first seen in the patient about seven months after he began receiving epidural stimulation.

Adds Burdick, "This may help bladder and bowel function even in patients who don't have the strength to undergo rigorous physical training like this patient"—who was an athlete and was in comparatively excellent physical condition before his injury.

The scientists aren't yet fully sure how these functions were regained—or, indeed, how the control of voluntary function was returned through the procedure. "Somehow, stimulation by the electrodes may have reactivated connections that were dormant or stimulated the growth of new connections," Burdick says. Almost certainly, reorganization of the neural pathways occurred below and perhaps also above the site of injury.

Notably, the patient had some sensation in his lower extremities after his injury, which means that the spinal cord was not completely severed; this may have affected the extent of his recovery.

The Food and Drug Administration (FDA) gave the research team approval to test five spinal-cord injury patients; the next patient will be matched with the first, in terms of age, injury, and physical ability, to see if the findings can be replicated. In subsequent trials, patients who have no sensation will be implanted with the device, to see if this influences the outcome.

"This is a significant breakthrough," says Susan Harkema of University of Louisville, the lead author of the paper in The Lancet. "It opens up a huge potential to improve the daily functioning of individuals."

"While these results are obviously encouraging, we need to be cautious, and there is much work to be done," says Edgerton.

One of the biggest obstacles is that the electrode array implanted in the human patient is FDA-approved for back pain only. The use of the FDA-approved device was meant "as a test to see if our concepts would work, providing us with additional ammunition to motivate the development of the arrays used in animal studies," says Burdick. The current FDA-approved arrays, he adds, have many limitations, "hence, the further development of the arrays that have currently only been tested in animals should provide even better human results in the future."

Using a combination of experimentation, computational models of the array and spinal cord, and machine-learning algorithms, Burdick and his colleagues are now trying to optimize the stimulation pattern to achieve the best effects, and to improve the design of the electrode array. Further advances in the technology should lead to better control of the stepping and standing processes.

In addition, he says, "our team is looking at other ways to apply the technology. We may move the array up higher on the spinal column to see if it could affect arms and hands, as well as the legs."

Burdick and his UCLA and University of Louisville colleagues hope that one day, some individuals with complete spinal-cord injuries will be able to use a portable stimulation unit and, with the assistance of a walker, stand independently, maintain balance, and perform some effective stepping. In addition, says Burdick, "our team believes that the protocol might prove useful in the treatment of stroke, Parkinson's, and other disorders affecting motor function."

The research in the paper, "Epidural stimulation of the lumbosacral spinal cord enables voluntary movement, standing, and assisted stepping in a paraplegic human," was funded by the National Institutes of Health with additional support provided by the Christopher and Dana Reeve Foundation. 

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Experiments Settle Long-Standing Debate about Mysterious Array Formations in Nanofilms

PASADENA, Calif.—Scientists at the California Institute of Technology (Caltech) have conducted experiments confirming which of three possible mechanisms is responsible for the spontaneous formation of three-dimensional (3-D) pillar arrays in nanofilms (polymer films that are billionths of a meter thick). These protrusions appear suddenly when the surface of a molten nanofilm is exposed to an extreme temperature gradient and self-organize into hexagonal, lamellar, square, or spiral patterns.

This unconventional means of patterning films is being developed by Sandra Troian, professor of applied physics, aeronautics, and mechanical engineering at Caltech, who uses modulation of surface forces to shape and mold liquefiable nanofilms into 3-D forms. "My ultimate goal is to develop a suite of 3-D lithographic techniques based on remote, digital modulation of thermal, electrical, and magnetic surface forces," Troian says. Confirmation of the correct mechanism has allowed her to deduce the maximum resolution or minimum feature size ultimately possible with these patterning techniques.

In Troian's method, arbitrary shapes are first sculpted from a molten film by surface forces and then instantly solidified in situ by cooling the sample. "These techniques are ideally suited for fabrication of optical or photonic components that exhibit ultrasmooth interfaces," she explains. The process also introduces some interesting new physics that only become evident at the nanoscale. "Even in the land of Lilliputians, these forces are puny at best—but at the nanoscale or smaller still, they rule the world," she says.

The experiments leading to this discovery were highlighted on the cover of the April 29 issue of the journal Physical Review Letters.

The experiments, designed to isolate the physics behind the process, are challenging at best. The setup requires two smooth, flat substrates, which are separated only by a few hundred nanometers, to remain perfectly parallel over distances of a centimeter or more.

Such an experimental setup presents several difficulties, including that "no substrate this size is truly flat," Troian says, "and even the world's smallest thermocouple is too large to fit inside the gap." In addition, she says, "the thermal gradient in the gap can exceed values of a million degrees per centimeter, so the setup undergoes significant expansion, distortion, and contraction during a typical run."

Transition between 3-D nanopillar arrays and striped structures in a polystyrene nanofilm subject to a thermal gradient of 105 degrees Celsius/cm.
Credit: Courtesy of E. McLeod and S. M. Troian, {LIS2T} lab/Caltech

In fact, all previous studies confronted similar challenges—leading to inaccurate estimates of the thermal gradient and the inability to view the formation and growth of the structures, among other problems. "To complicate matters," Troian says, "all of the previous data in the literature were obtained at very late stages of growth, far beyond the regime of validity of the theoretical models," Troian says.

The Caltech experiments solved these challenges by reverting to in situ measurements. The researchers replaced the top cold substrate with a transparent window fashioned from a single crystal sapphire, which permitted them to view directly the developing formations. They also used white light interferometry to help maintain parallelism during each run and to record the emerging shape and growth rate of emerging structures. Finite element simulations were also used to obtain much more accurate estimates of the thermal gradient in the tiny gap.

"When all is said and done, our results indicate that this formation process is not driven by electrostatic attraction between the film surface and the nearby substrate—similar to what happens when you run a comb through your hair—or pressure fluctuations inside the film from reflections of acoustic phonons—the collective excitations of molecules—as once believed, Troian explains. "The data simply don't fit these models, no matter how hard you try," she says. The data also did not seem to fit a third model based on film structuring by thermocapillary flow—the flow from warmer to cooler regions that accompanies surface temperature variations.

Troian proposed the thermocapillary model several years ago. Calculations for this "cold-seeking instability" suggest that nanofilms are always unstable in response to the formation of 3-D pillar arrays, regardless of the size of the thermal gradient. Tiny protrusions in the film experience a slightly cooler temperature than the surrounding liquid because of their proximity to a cold target. The surface tension of those tips is greater than that of the surrounding film. This imbalance generates a very strong surface force that "pulls" fluid up and "into the third dimension," she says. This process easily gives rise to large area arrays of dimples, ridges, pillars, and other shapes. A nonlinear version of the model suggests how cold pins can also be used to form more regular arrays.

Scanning electron micrograph of solidified protrusions in a 98 nm polystyrene film guided by a remote hexagonal array of cold pins.
Credit: Courtesy of E. McLeod and S. M. Troian, {LIS2T} lab/Caltech.

Troian was initially disappointed that the measurements did not match the theoretical predictions. For example, the prediction for the spacing between protrusions was off by a factor of two or more. "It occurred to me that certain properties of the nanofilm to be input into the model might be quite different than those literature values obtained from macroscopic samples," she notes.

She enlisted the advice of mechanical engineer Ken Goodson at Stanford, an expert on thermal transport in nanofilms, who confirmed that he'd also noticed a significant enhancement in the heat-transfer capability of certain nanofilms. Further investigation revealed that other groups around the world have begun reporting similar enhancement in optical and other characteristics of nanofilms. "And voila! … by adjusting one key parameter," Troian says, "we obtained perfect agreement between experiment and theory. How cool is that!"

Not satisfied by these findings, Troian wants to launch a separate study to find the source of these enhanced properties in nanofilms. "Now that our horizon is clear, I guarantee we won't sit still until we can fabricate some unusual components whose shape and optical response can only be formed by such a process."

The paper, "Experimental Verification of the Formation Mechanism for Pillar Arrays in Nanofilms Subject to Large Thermal Gradients," was coauthored by Euan McLeod and Yu Liu of Caltech. The work was funded by the National Science Foundation.

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Caltech Faculty Receive Early Career Grants

Four Caltech faculty members are among the 65 scientists from across the nation selected to receive five-year Early Career Research Awards from the U.S. Department of Energy (DOE). The grant winners, who were selected from a pool of about 1,150 applicants, are:

  • Guillaume Blanquart, assistant professor of mechanical engineering, who will develop a chemical model of the inner structure and of the formation of soot particles—black carbon particles formed during the incomplete combustion of hydrocarbon fuels that can cause health problems and adverse effects on the environment—that will aid the development of models that predict emissions from car and truck engines, aircraft engines, fires, and more.

  • Julia R. Greer, assistant professor of materials science and mechanics, who will use nanomechanical experimental and computational tools to isolate and understand the role of specific tailored interfaces and deformation mechanisms on the degradation of properties of materials subjected to helium irradiation. Elucidating these mechanisms will provide insight into requirements for advanced materials for current and next-generation nuclear reactors.

  • Chris Hirata, assistant professor of astrophysics, who will be conducting theoretical studies of cosmological observables—such as galaxy clustering—that are being used to probe dark energy and dark matter and to search for gravitational waves from inflation.

  • Ryan Patterson, assistant professor of physics, who will develop new techniques for readout, calibration, and particle identification for the NOvA long-baseline neutrino experiment at Fermilab, which will investigate neutrino oscillations—the conversion of neutrinos of one type (or "flavor") into another.

The Early Career Research Program, which is funded by the DOE's Office of Science, is "designed to bolster the nation's scientific workforce by providing support to exceptional researchers during the crucial early career years, when many scientists do their most formative work," according to the DOE announcement, and is intended to encourage scientists to focus on research areas that are considered high priorities for the Department of Energy.

To be eligible for an award, a researcher must have received a doctorate within the past 10 years and be an untenured, tenure-track assistant or associate professor at a U.S. academic institution or a full-time employee at a DOE national laboratory.

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Strong, Tough, and Now Cheap: Caltech Researchers Have New Way to Process Metallic Glass

PASADENA, Calif.—Stronger than steel or titanium—and just as tough—metallic glass is an ideal material for everything from cell-phone cases to aircraft parts. Now, researchers at the California Institute of Technology (Caltech) have developed a new technique that allows them to make metallic-glass parts utilizing the same inexpensive processes used to produce plastic parts. With this new method, they can heat a piece of metallic glass at a rate of a million degrees per second and then mold it into any shape in just a few milliseconds.

"We've redefined how you process metals," says William Johnson, the Ruben F. and Donna Mettler Professor of Engineering and Applied Science. "This is a paradigm shift in metallurgy." Johnson leads a team of researchers who are publishing their findings in the May 13 issue of the journal Science.

"We've taken the economics of plastic manufacturing and applied it to a metal with superior engineering properties,” he says. "We end up with inexpensive, high-performance, precision net-shape parts made in the same way plastic parts are made—but made of a metal that's 20 times stronger and stiffer than plastic.” A net-shape part is a part that has acquired its final shape.

Metallic glasses, which were first discovered at Caltech in 1960 and later produced in bulk form by Johnson's group in the early 1990s, are not transparent like window glass. Rather, they are metals with the disordered atomic structure of glass. While common glasses are generally strong, hard, and resistant to permanent deformation, they tend to easily crack or shatter. Metals tend to be tough materials that resist cracking and brittle fracture—but they have limited strength. Metallic glasses, Johnson says, have an exceptional combination of both the strength associated with glass and the toughness of metals.

A piece of metallic glass is heated and squished in just 10 milliseconds.
Credit: Georg Kaltenboeck

To make useful parts from a metallic glass, you need to heat the material until it reaches its glass-transition phase, at about 500–600 degrees C. The material softens and becomes a thick liquid that can be molded and shaped. In this liquid state, the atoms tend to spontaneously arrange themselves to form crystals. Solid glass is formed when the molten material refreezes into place before its atoms have had enough time to form crystals. By avoiding crystallization, the material keeps its amorphous structure, which is what makes it strong.

Common window glass and certain plastics take from minutes to hours—or longer—to crystallize in this molten state, providing ample time for them to be molded, shaped, cooled, and solidified. Metallic glasses, however, crystallize almost immediately once they are heated to the thick-liquid state. Avoiding this rapid crystallization is the main challenge in making metallic-glass parts.

Previously, metallic-glass parts were produced by heating the metal alloy above the melting point of the crystalline phase—typically over 1,000 degrees C. Then, the molten metal is cast into a steel mold, where it cools before crystallizing. But problems arise because the steel molds are usually designed to withstand temperatures of only around 600 degrees C. As a result, the molds have to be frequently replaced, making the process rather expensive. Furthermore, at 1,000 degrees C, the liquid is so fluid that it tends to splash and break up, creating parts with flow defects.

If the solid metallic glass is heated to about 500–600 degrees C, it reaches the same fluidity that liquid plastic needs to have when it's processed. But it takes time for heat to spread through a metallic glass, and by the time the material reaches the proper temperature throughout, it has already crystallized.

So the researchers tried a new strategy: to heat and process the metallic glass extremely quickly. Johnson's team discovered that, if they were fast enough, they could heat the metallic glass to a liquid state that's fluid enough to be injected into a mold and allowed to freeze—all before it could crystallize.

To heat the material uniformly and rapidly, they used a technique called ohmic heating. The researchers fired a short and intense pulse of electrical current to deliver an energy surpassing 1,000 joules in about 1 millisecond—about one megawatt of power—to heat a small rod of the metallic glass.

A piece of metallic glass being heated and squished in milliseconds, as seen in these infrared snapshots.
Credit: Joseph P. Schramm

The current pulse heats the entire rod—which was 4 millimeters in diameter and 2 centimeters long—at a rate of a million degrees per second. "We uniformly heat the glass at least a thousand times faster than anyone has before," Johnson says. Taking only about half a millisecond to reach the right temperature, the now-softened glass could be injected into a mold and cooled—all in milliseconds. To demonstrate the new method, the researchers heated a metallic-glass rod to about 550 degrees C and then shaped it into a toroid in less than 40 milliseconds. Despite being formed in open air, the molded toroid is free of flow defects and oxidation.

In addition, this process allows researchers to study these materials in their molten states, which was never before possible. For example, by heating the material before it can crystallize, researchers can examine the crystallization process itself on millisecond time scales. The new technique, called rapid discharge forming, has been patented and is being developed for commercialization, Johnson says. In 2010, he and his colleagues started a company, Glassimetal Technology, to commercialize novel metallic-glass alloys using this kind of plastic-forming technology.

The other authors on the Science paper, "Beating crystallization in glass-forming metals by millisecond heating and processing," are Caltech's Georg Kaltenboeck, Marios D. Demetriou, Joseph P. Schramm, Xiao Liu, Konrad Samwer (a visiting associate from the University of Gottingen, Germany), C. Paul Kim, and Douglas C. Hofmann. This research benefited from support by the II-VI Foundation.

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Engineering Design Competition: "Extreme Recycling"

Congratulations to Chris Hallacy, Brad Saund, and Janet Chen for their victory March 8 in the 26th annual ME 72 engineering design competition. This year's theme: "Extreme Recycling." The mission: Design, build, and deploy two vehicles and traverse difficult terrain (water, sand, rocks, and wood chips, with one type of terrain in each of four different 6' x 10' boxes) to collect plastic water bottles, aluminum cans, and steel cans. During each five-minute round, the bots were to transport the recyclables and drop them (ideally, sorted by type, and—in the case of aluminum cans—crushed to less than half of their vertical height) into recycling bins, before scurrying back to the starting zone.

Twenty weeks earlier, at the start of ME 72—Caltech's undergraduate engineering design laboratory class—students were given a budget (ultimately $1200, of which up to $800 could be spent in the Caltech stockrooms) to purchase whatever they needed to build their bots. The ultimate designs followed a few basic themes: bots with scoopers and grippers, to grab the bottles and cans, and bots with baskets, to haul the loot. Other design features included ramps to wedge under opponent bots and trip them up.

Hallacy, Saund, and Chen—a.k.a. team "BRB"—bested five other teams without dropping a heat during the double-elimination contest. In the final round, against team Wall-E—headed by Keir Gonyea, Chris Pombrol, Allen Chen, and Gerardo Morabito—BRB scored first, delivering a plastic bottle to the recycling bin, and hung on (including by literally hanging on to one of the Wall-E bots) for the win.

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Young Caltech Engineers Recognized for Innovative Work in Disease Diagnostic Technologies

$30,000 Lemelson-MIT Collegiate Student Prizes announced; four leading institutes celebrate winners

PASADENA, Calif.—California Institute of Technology (Caltech) graduate student Guoan Zheng is the recipient of the 2011 $30,000 Lemelson-MIT Caltech Student Prize

Zheng was among the four $30,000 Lemelson-MIT Collegiate Student Prize winners announced Wednesday, March 9. He was recognized for his innovative development of an on-chip, inexpensive microscopy imaging technology with many potential applications, including improved diagnostics for malaria and other blood-borne diseases in the developing world.

Zheng, a graduate student in electrical engineering working in the laboratory of Changhuei Yang, professor of electrical engineering and bioengineering, designed a simple, cost-effective, high-resolution on-chip microscope called a sub-pixel resolving optofluidic microscope (SROFM). The technology is suitable for biological research and enables more affordable clinical and field diagnostics. A prolific inventor, Zheng developed an additional low-cost 500-megapixel microscopy imaging system as well as a surface-wave-enabled darkfield aperture (SWEDA), a nanophotonic structure that can be used to boost the detection sensitivity of image sensors.

Zheng and two other finalists presented their inventions to a judging panel and the Caltech community on January 27. In his presentation, Zheng demonstrated his strong interest in the integration of complementary metal-oxide semiconductor (CMOS) technology with image processing, computer vision, microfluidics, and nanotechnology for the design of next-generation low-cost biomedical imaging and sensing devices. His three inventions are all aimed at improving disease diagnostics in the developing world.

According to Yang, "Guoan is a terrific engineer and researcher. His most significant invention to date is his development of SROFM, an original and highly practical approach for designing microscopes. On a different front, Guoan has also paved the way for the next generation of pixel design with his highly innovative work on SWEDA."

Zheng was born and raised in Canton, China. He received his undergraduate degree with honors in electrical engineering from Zhejiang University in Hangzhou, China, and his master's degree in electrical engineering from Caltech in 2008. Zheng is a coauthor on 13 peer-reviewed journal publications. Driven by what he sees as a need in the market for low-cost diagnostic tools, he plans to further develop his biomedical products with the goal of starting his own medical device company.

The Caltech selection committee also acknowledged finalist Wendian "Leo" Shi for the invention of the "μCyto," a portable lab-on-a-chip system for determining white blood cell counts for point-of-care diagnostics. Shi will receive a $10,000 award made possible through the support of Caltech alumnus Michael Hunkapiller (PhD '74). Also an electrical engineering graduate student, Shi works in the lab of Yu-Chong Tai, professor of electrical engineering and mechanical engineering.

In his presentation, Shi described an innovative technology that provides a low-cost alternative to conventional blood counters. A five-part white blood cell (WBC) differential count is one of the most useful clinical tests performed in hospitals to directly evaluate how the immune system is functioning. Shi's low-cost, portable blood counter provides important diagnostic information for conditions such as leukemia, infections, allergies, and immunodeficiency, and can be used to monitor a patient's recovery during therapy. 

Shi's technology is the first successful demonstration of a miniaturized blood counter with a complete WBC five-part differential, and it opens up new possibilities for providing basic medical care to people living in remote rural areas where medical diagnostic tools are not readily accessible. According to Shi, the system can be easily expanded to incorporate the diagnosis of many more diseases by transferring test results wirelessly to doctors in central hospitals.

Shi was born in Zhejiang, China, and earned his BS in microelectronics from Peking University in Beijing. He moved to California in 2007 to complete his master's degree in electrical engineering and continue graduate work at Caltech. Inspired by his mother's career as a doctor, Shi plans to work in the medical device industry and would like to start his own company in the field.

"The innovative work of Zheng and Shi illustrates the impact engineers can have on addressing the greatest challenges faced by our society. They are two electrical engineering students who have chosen to focus their research on improving diagnostic tools for diseases such as malaria and leukemia," says Ares Rosakis, chair of Caltech's Division of Engineering and Applied Science and the Theodore von Kármán Professor of Aeronautics and professor of mechanical engineering.

"The Lemelson-MIT Collegiate Student Prize winners have shown their potential to invent broadly and bring new innovations into the world," says Joshua Schuler, executive director of the Lemelson-MIT Program. "These inventive achievements and the students' creativity, persistence, and overall collaboration must be celebrated at the collegiate level."

Lemelson-MIT Collegiate Student Prize Recipients

Prizes were also awarded to students at the University of Illinois at Urbana-Champaign, MIT, and Rensselaer Polytechnic Institute. The following winners of the annual Lemelson-MIT Collegiate Student Prize were announced March 9 at their respective universities:

-         2011 Lemelson-MIT Illinois Student Prize Winner

Lemelson-MIT Illinois Student Prize winner Scott Daigle developed a system that utilizes automatic gear shifting to reduce the efforts exerted by wheelchair operators. Daigle's company, IntelliWheels, Inc., has an entire suite of products to improve the everyday actions of wheelchair users.

-         2011 Lemelson-MIT Student Prize Winner

Lemelson-MIT Student Prize winner Alice A. Chen developed an assortment of innovations with promising drug development implications, including a humanized mouse with a tissue-engineered human liver designed to bridge a gap between laboratory animal studies and clinical trials.

-         2011 Lemelson-MIT Rensselaer Student Prize Winner

Lemelson-MIT Rensselaer Student Prize winner Benjamin Clough has demonstrated a new technique that employs sound waves to boost the distance from which researchers can use terahertz spectroscopy to remotely detect hidden explosives, chemicals, and other dangerous materials.

ABOUT THE LEMELSON-MIT PROGRAM

Celebrating innovation, inspiring youth

The Lemelson-MIT Program celebrates outstanding innovators and inspires young people to pursue creative lives and careers through invention.

Jerome H. Lemelson, one of U.S. history's most prolific inventors, and his wife Dorothy founded the Lemelson-MIT Program at the Massachusetts Institute of Technology in 1994. It is funded by the Lemelson Foundation and administered by the School of Engineering. The foundation sparks, sustains, and celebrates innovation and the inventive spirit. It supports projects in the United States and developing countries that nurture innovators and unleash invention to advance economic, social, and environmentally sustainable development. To date, the Lemelson Foundation has donated or committed more than $150 million in support of its mission.

About the Lemelson-MIT Caltech Student Prize: The $30,000 Lemelson-MIT Caltech Student Prize is funded through a partnership with the Lemelson-MIT Program, which has awarded the $30,000 Lemelson-MIT Student Prize to outstanding student inventors at MIT since 1995. 

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Katie Neith
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Caltech Student Recognized as a "New Face" of Engineering

For Javad Lavaei, a PhD candidate in the Division of Engineering and Applied Science at Caltech, seeking a career in engineering came naturally.

"I was very interested in learning advanced mathematics when I was in high school," says Lavaei. "I had a craving to put my knowledge into practice and to design real-world systems."

With strong family support and motivational high-school teachers who encouraged his interest in engineering, Lavaei pursued and completed a bachelor's and master's degree in electrical engineering. Now, he has the chance to influence other young students to pursue engineering careers as part of the New Faces of Engineering program.

Lavaei was highlighted for his "interesting and unique work" by the program, which is organized by the National Engineers Week Foundation and recognizes engineers who have been in the workplace five years or less and have shown outstanding ability in projects that significantly impact public welfare or further professional development and growth.

"I am very happy that my work has been recognized by senior engineers and that they have considered me a successful engineer," says Lavaei, who is working toward a degree in control and dynamical systems. His current research focuses on techniques specialized for power systems that could potentially save energy, reduce costs, and improve reliability, such as the design of a smart grid. A smart grid utilizes digital technology to improve how electricity travels from power plants to consumers. In the past, he has worked in many different areas of electrical and computer engineering, including control, circuits, communications, and networks.

Lavaei encourages students to apply their enthusiasm for engineering to improving communications infrastructures, electrical power grids, and other areas that can benefit society. 

"I think it's very exciting to work on important engineering problems and find solutions for them that can, in principle, affect everyone's lives in the future," he says. "Students can be very successful in engineering if they have a passion for understanding and/or designing real-world systems."

The National Engineers Week Foundation is a coalition of more than 100 engineering societies, major corporations, and government agencies that seeks to increase public understanding and appreciation of engineers' contributions to society. For more information, visit www.eweek.org.

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Katie Neith
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Daraio Awarded Sloan Fellowship

Caltech's Chiara Daraio is among this year's crop of Sloan Research Fellows. Daraio, who this year was promoted from assistant to full professor of aeronautics and applied physics, is one of 118 faculty from across the country to receive the two-year, $50,000 fellowship, given to early-career scientists and scholars in recognition of achievement and the potential to contribute substantially to their fields.

"It's a great honor for me to receive a Sloan Research Fellowship, a very competitive award," says Daraio, whose research focuses on the design and testing of new materials with "unprecedented" mechanical properties. "We design new materials by assembling fundamental building blocks that interact nonlinearly, and we can choose these nonlinear interactions by controlling, for example, the shape and material properties of the building blocks. The materials we design can have several practical applications, from acoustic imaging to shock absorption."

"I am particularly pleased because the fellowship is awarded primarily in the basic sciences—physics, in my case—and this means that our research is being recognized also for its contribution to the basic sciences, beyond its engineering origins," says Daraio. Her group will use the funds to support a new research area related to the study of strongly nonlinear mechanical phenomena at micro- and nanoscales.

Presented annually since 1955 by the Sloan Foundation, the fellowships are awarded in chemistry, computer science, economics, mathematics, evolutionary and computational molecular biology, neuroscience, and physics. Potential fellows must be nominated by their peers and are subsequently selected by an independent panel of senior scholars. Once named, Sloan Research Fellows are free to pursue whatever research most interests them, and they can use their fellowship funds in a wide variety of ways. Thirty-eight Sloan Research Fellows have gone on to win the Nobel Prize in their fields.

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Caltech-Led Team Pinpoints Aggression Neurons in the Brain

Finding could lead to new treatments for impulsive violence

PASADENA, Calif.—Where does violence live in the brain? And where, precisely, does it lay down its biological roots? With the help of a new genetic tool that uses light to turn nerve cells on and off, a team led by researchers at the California Institute of Technology (Caltech) has tracked down the specific location of the neurons that elicit attack behaviors in mice, and defined the relationship of those cells to the brain circuits that play a key role in mating behaviors.

The researchers’ hope is that these insights might lead to treatments that can specifically address impulsive violence, a category of behavior that has been historically difficult to grapple with from a medical or psychological perspective.

In a study published in this week's issue of the journal Nature, the researchers were not only able to localize the neuronal circuits mediating attack behavior in mice, but were able to determine that these circuits are "intimately associated, deeply intertwined," with another basic social-behavioral drive—mating—according to David J. Anderson, the Benzer Professor of Biology at Caltech and a Howard Hughes Medical Institute investigator.

Indeed, the neurons for violence and mating live so close together, in a brain region known as the ventrolateral subdivision of the ventromedial hypothalamus (VMH), that "they are like a salt-and-pepper mixture," says Anderson.

And if you think of the brain as the world and the hypothalamus as a country, he adds, then the ventromedial hypothalamus is like a state and the ventrolateral subdivision is like a city within that state. "We've found that these 'mating' and 'fighting' neurons are not only located in the same city, but potentially in the same neighborhood," he says.

To determine whether aggression and mating involve the same—or, rather, distinct but intermingled—neurons, Dayu Lin, a former postdoctoral fellow in Anderson's lab and now an assistant professor at New York University, carried out a series of challenging electrophysiological recording experiments in the VMH. Because the VMH is located deep within the brain, it is exceedingly difficult to target accurately. But by inserting a bundle of 16 wire electrodes into this region, Lin was able to get recordings from multiple neurons during repeated episodes of fighting or mating. "It's the first time in which it's been possible to record electrical activity from deep-brain hypothalamic structures in animals while they are engaging in aggressive and mating behaviors," says Anderson.

Using software developed by Allen E. Puckett Professor of Electrical Engineering Pietro Perona and senior postdoctoral scholar Piotr Dollar—and with the help of several Caltech undergraduates—the researchers annotated behavioral changes on a frame-by-frame basis from video taken at the same time as the electrical recordings were performed. This annotation allowed them to make correlations between neuronal activity and behavior with a temporal resolution of approximately 30 milliseconds.

These experiments indicated that while there is some overlap between "mating" neurons and "fighting" neurons, the majority of these cells are distinct, despite their close proximity. Perhaps most surprising, Anderson notes, is the way that the neurons responsible for aggression and mating communicate—or, rather, how they shut each other up. Sex and violence, it seems, are actually at odds: a neuron that is turned on during aggressive behavior will turn off during mating, and vice versa. "We found that they talk to each other in an inhibitory way," he says.

But a correlation between neuronal activity and fighting behavior doesn't indicate whether the activity causes the behavior or the behavior causes the activity. And so Lin, Anderson, and colleagues carried out experiments to activate or inhibit VMH neurons, to distinguish between those alternatives and to determine the effect of such manipulations on behavior.

In order to activate neurons in the VMH, they used a technique known as optogenetic stimulation. Using a disabled virus as a kind of "disposable molecular syringe," Lin injected VMH neurons with DNA that carries the code for channelrhodopsin-2, a protein from blue-green algae that increases neuronal activity in response to blue light. The sensitized neurons could then be turned on or off with the literal flip of a light switch, allowing the scientists to watch what happens to the behavior of an individual mouse.

Remarkably, says Anderson, for mice in which the injection was targeted to the correct location, blue light induced an attack—even toward an inanimate object such as an inflated latex glove. Conversely, using a technique developed by Caltech’s Bren Professor of Biology Henry A. Lester that allowed the scientists to genetically inhibit neuronal activity, Lin and colleagues were able to show that neuronal activity in the VMH was necessary for normal aggressive behavior, as well.

"This answers an important, long-standing question in the field," says Anderson. "Are regions of the brain that can evoke aggression when artificially stimulated actually necessary for normal aggressive behavior? In this case, the answer is clearly 'yes.'"

The researchers also found that stimulating a male to be aggressive toward a female became more difficult as a mating encounter progressed to its consummatory phase. This result was consistent with the observation that neurons activated during fighting appear to become inhibited in the presence of a female. "The question," says Anderson, "is how that inhibition is achieved."

The answer may lead to new areas of research—and, perhaps, to new treatments for impulsive, violent behaviors. Specifically, notes Anderson, scientists can begin thinking about treatments that target violence-begetting neurons while sparing those involved in normal sexual behavior.

"For the last 500 years, we've really had no viable treatments for pathological violence other than execution or imprisonment," says Anderson. "And part of the reason is that we haven't understood enough about the basic neurobiology of aggression. The new studies are an important step in that direction."

In addition, he says, "mapping out the brain circuitry of aggression will provide a framework for understanding where and how in the brain genetic and environmental influences—nature vs. nurture—exert their influences on aggressive behavior."

The other authors on the Nature paper, "Functional identification of an aggression locus in the mouse hypothalamus," in addition to Anderson, Lin, Dollar, and Perona, are Caltech postdoctoral scholar Hyosang Lee and Maureen Boyle and Ed Lein from the Allen Institute for Brain Science in Seattle.

Their work was funded by the Weston-Havens Foundation, the Jane Coffin Childs Foundation, and the Howard Hughes Medical Institute.

 

Writer: 
Lori Oliwenstein
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Two Caltech Professors Named to National Academy of Engineering

Two prominent Caltech faculty have been named members of the National Academy of Engineering (NAE). Election to the NAE is among the highest professional distinctions accorded to an engineer, says NAE President Charles M. Vest.

Ares J. Rosakis, the Theodore von Karman Professor of Aeronautics, professor of mechanical engineering, and chair of the Division of Engineering and Applied Science, was elected for his "discovery of intersonic rupture, contributions to understanding dynamic failure, and methods to determine stresses in thin-film structures," according to the NAE.

Michael Hoffmann, the James Irvine Professor of Environmental Science, was elected for his work on "oxidative treatment technologies for the removal of organic and inorganic contaminants from water."

Writer: 
Lori Oliwenstein
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