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June 26, 2014

Research Notes

Bioengineer earns $2.9 million brain implant grant

Xinyan “Tracy” Cui, bioengineering faculty member in the Swanson School of Engineering, has received a five-year, $2.9 million grant from the National Institutes of Health (NIH) to improve brain-computer interface technology.

Less than two years ago, a brain-computer interface designed at the University allowed Jan Scheuermann, who has quadriplegia, to control a robotic arm solely with her thoughts. Such technology soon may help other patients with quadriplegia or amputated limbs.

Cui will focus on the microelectrode arrays, or brain implants, that are used to connect mind and machine. As the primary investigator, she will explore ways to coat the microelectrodes with biological molecules that may strengthen the connection between the brain implants and computers that operate devices like robotic arms.

Research has shown that, over time, microelectrode arrays can elicit an inflammatory response and cause damage to neurons, weakening the link. While the harm to the patient isn’t significant, poorer recordings of neural impulses can limit the functionality of the technology and the quality of information reaped by researchers.

Cui said: “For the first few months, the data are good, but it starts to decline. It’s a common trend to see the amplitude of the recorded signal go down, and it becomes lost in the noise. After a year, we lose half the channels. What we hope to do is camouflage (the microelectrode needles) with biochemicals that can escape the immune surveillance response and protect neurons around the electrodes.”

Cui has high hopes for a cell adhesion molecule called L1, which has shown positive results in animal models. In addition to gaining better understanding of the mechanisms behind L1’s preliminary success, Cui also plans to pursue and test several other targets.

Andrew Schwartz, the neurobiology faculty member leading a study of the robotic arm technology used by Scheuermann and serving as a co-investigator on Cui’s team, believes in the potential of the project. “We did one array, and we had spectacular results,” he said. “We had very nice recordings with large signals, and they lasted longer than what we would normally see.”

Schwartz said that the initial experiments have shown that the coating extends the viability of neural recording via microelectrode arrays by about six months beyond what is now a nine- to 12-month window.

The grant also will be used to explore a new microscopy technique that will allow Cui and colleagues to monitor the function of L1 and other tested molecules in a living animal.

“In vivo imaging will allow us to see which neurons are firing and which are not active and, therefore, not being recorded,” she said.

Cui’s work could advance not only brain-computer interface technology but also other technologies that use microelectrode arrays to help restore sight, hearing, movement, ability to communicate and cognitive function.

Co-investigators are School of Medicine faculty members Carl Lagenaur, neurobiology, and Alberto Vazquez, radiology, as well as T.K. Koza in the Swanson school’s bioengineering program.

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UCSUR awards grants for neighborhood studies

The University Center for Social and Urban Research (UCSUR) has given two Steven D. Manners Faculty Development Awards to promising research projects in the social, behavioral and policy sciences on campus.

One award, to epidemiology faculty members Anthony Fabio and Dara Mendez, funds a project titled “The Development of a Measure of Neighborhood Well-being for Pittsburgh Neighborhoods.” This study aims to develop, through the use of the data included in the Pittsburgh Neighborhood and Community Information System, a neighborhood well-being index. This index will be used as a guide for identifying neighborhoods with positive or negative attributes related to public health.

The researchers plan to apply this index to two ongoing studies: an analysis of the effects of the Consol Energy Center and the Rivers Casino on neighborhood level crime, and the relationship between neighborhood environments and pregnancy and birth outcomes. The results are expected to be a resource for other researchers and advocates in the Pittsburgh community conducting work related to the influence of the neighborhood on health and well-being, particularly in addressing issues of equity in the region.

The second award, to University of Pittsburgh Cancer Institute faculty member Linda Barry Robertson, will fund “Social Stressors, Air Pollution and Cancer in Allegheny County.” This study will develop methods to explore multifaceted, and potentially interactive, risk factors for cancer — including exposures to neighborhood psychosocial stressors and air pollution, and individual factors including smoking, drinking, obesity, physical activity and psychological distress.

Robertson also plans to map local spatial patterns in two important risk factors for cancer — air pollution and psychosocial stress — in an effort to develop refined, testable hypotheses on mechanistic pathways for different cancer outcomes.

These grants support pilot research with scientific merit and a strong likelihood that the project will lead to subsequent external peer reviewed funding. They honor the memory of Steven Manners, a sociologist who began working at the center in 1974 and served as its assistant director from 1989 until his death in September 2000. His research and service to the center and the University community were dedicated to improving social conditions in the urban environment.

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Depression associated with earlier deaths in type 1 diabetics

People with type 1 diabetes have a higher risk of premature death as their number of depressive symptoms increases, a Graduate School of Public Health study revealed.

The research used data collected through the Pittsburgh Epidemiology of Diabetes Complications Study (PEDCS), a long-term study of health complications in people with type 1 diabetes.

Said senior author Trevor Orchard, epidemiology faculty member: “Through the 25 years that we’ve been running this study, we’ve found that there’s a lot more to diabetes than high blood sugar. This link between premature mortality and depression adds to our previous findings, which show that depressive symptomatology predicts cardiovascular disease and demonstrates that doctors need to consider more than adjusting insulin doses when treating type 1 diabetes.”

Lead author Cassie Fickley, a doctoral student in Orchard’s department, analyzed data on 458 study participants with type 1 diabetes who were assessed using the Beck Depression Inventory, a 32-point scale that measures depressive symptoms ranging from loss of appetite to suicidal tendencies. People who score 16 or more points are considered likely to be clinically depressed.

Said Fickley: “For every one-point increase on the scale, participants showed a 4 percent increase in risk for mortality, even after controlling for other relevant factors, such as age, gender, smoking, cholesterol levels and high blood pressure. That’s a significant increase and is something we’ll need to explore more to determine if treating depression would translate into lower mortality in people with type 1 diabetes.”

Type 1 diabetes usually is diagnosed in children and young adults and occurs when the body does not produce insulin, a hormone that is needed to convert sugar into energy. The disease can lead to nerve, kidney, eye and heart complications but can be controlled with insulin therapy and other treatments.

PEDCS is an investigation to document long-term complications of type 1 diabetes among patients at Children’s Hospital between 1950 and 1980. Funded by NIH, the study recently was renewed for another five years. Its latest findings were presented in a press conference at the American Diabetes Association scientific sessions.

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Engineering innovation incremental, psych study finds

Is finding that “new” engineering invention a massive mental leap from point A to point B, or are there scores of unnoticed intermediate steps in between?

Christian Schunn, a psychology faculty member and senior scientist at the Learning Research and Development Center, and Joel Chan, a psychology graduate student in the Dietrich School of Arts and Sciences, believe that not enough has been done to understand how engineers create. Understanding the process may provide a road map for speeding up innovation. Their recently published paper online in Cognitive Science explored the workings of the creative engineering mind by examining the process in real life.

Said Schunn: “Most companies make all their money on new products. They barely break even on old products. They have to innovate to be viable, and that’s a hard path to follow.” In the pursuit of innovation, companies pay big money to consultants to help spur creativity. “But little of what they do is based on research,” he added.

Using multiple hours of transcripts of a professional engineering team’s “brainstorming” sessions to break down the conversation systematically, the researchers looked for the path by which thought A led to thought B that led to breakthrough C.

“We want to understand the nature of cognitive limitations,” Schunn said. “Why do we get stuck (on an idea), what kinds of things get us unstuck and why do they work?”

They found that new ideas didn’t spring fully formed after massive cognitive leaps. Creativity is a stepwise process in which idea A spurs a new but closely related thought, which prompts another incremental step, and the chain of little mental advances sometimes ends with an innovative idea in a group setting.

Commenting on Thomas Edison’s dictum that genius is 1 percent inspiration and 99 percent perspiration, Schunn concluded that “inspiration creates some … perspiration.”

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Formula content doesn’t prevent development of diabetes antibody

Early findings from the first large international trial to try to prevent type 1 diabetes show that infants at risk for the disease who were fed a special baby formula that lacks complex cow milk proteins still made antibodies against the insulin-producing cells of the pancreas by the time the youngest children studied were 6 years old. Previous studies suggested the experimental formula might prevent the development of the auto-antibodies, which represent inflammatory changes in the organ.

But that doesn’t mean the children definitely will develop type 1 diabetes as they get older, cautioned researchers at Children’s Hospital, led by School of Medicine pediatrics faculty member Dorothy Becker, U.S. principal investigator for the study. Pitt is the coordinating center for the American arm of the study. The results were published in the Journal of the American Medical Association.

In type 1 diabetes, the body’s immune system attacks its own pancreatic beta cells, which make insulin to regulate blood sugar levels. That autoimmune process is thought to start very early in life, explained Becker. Some smaller studies and animal experiments have shown that exposure during infancy to complex foreign proteins, such as the cow milk proteins in conventional baby formula, is associated with the presence of these autoimmune antibodies in children who have a parent or sibling with the condition and other indications of genetic risk.

Said Becker: “This has been a controversial issue, in part because different natural history studies have come to different conclusions. We hope that when our intervention trial concludes in February 2017, which is when all the participating children will be at least 10 years old, we should have enough evidence to say whether or not this experimental formula can prevent them from getting type 1 diabetes.”

From 2002 to 2007 at 78 study sites in 15 countries, the “Trial to Reduce IDDM in the Genetically at Risk,” or TRIGR, research group randomly assigned 1,078 high-risk infants to be weaned to a “hydrolyzed” formula made almost completely with smaller, less complex casein proteins, and 1,081 to get conventional formula, which is made with 80 percent cow milk proteins and 20 percent of the hydrolyzed casein protein. The two formulas were similar in taste and smell so that neither the parents nor researchers could tell the difference between them. Each baby’s parents made their own decisions about breastfeeding and age of weaning to formula.

Blood samples from the umbilical cord and at 3, 6, 9, 12, 18 and 24 months of age, and yearly after that to age 10, were tested for antibody levels. After an average of seven years of follow-up — the youngest participants are now 6 — the researchers found no differences in antibody levels between the two groups.

“This tells us that the kind of formula the baby drinks doesn’t affect the inflammatory changes going on in the pancreas,” Becker said. “But it doesn’t tell us yet whether they will develop diabetes. In one animal study, mice that were fed the experimental formula had the inflammatory markers, but diabetes was almost totally prevented using the same experimental formula. That could be the case with these children, too.”

The TRIGR study group includes researchers from six centers in the U.S., centers in Scandinavia and centers throughout Canada, Australia and Europe.

The project was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the special statutory funding program for type 1 diabetes research and digestive and kidney diseases, both part of NIH; the Canadian Institutes of Health Research; the Juvenile Diabetes Research Foundation International, and the Commission of the European Communities.

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NSF funds sustainably produced magnets for electric generation

A more energy-efficient and less time-consuming method to produce permanent magnets for power generation in machines from electric cars to windmills is the potential of a National Science Foundation grant to engineering researchers at the Swanson School of Engineering and Alcoa Technical Center in New Kensington.

The proposal, “Manufacturing of Nanostructure-Enhanced Mn-Al-base Materials via Modulated Machining and Thermomechanical Consolidation for High-Performance Magnets” was awarded a $299,998 NSF Grant Opportunity for Academic Liaison with Industry (GOALI) award for three years.

The research will be led by Jörg M. K. Wiezorek, faculty member in mechanical engineering and materials science, with co-PIs M. Ravi Shankar, faculty member and Whiteford Faculty Fellow in industrial engineering and Hasso Weiland at the Alcoa center. They use a machining-based process combined with low-temperature consolidation to generate dense bulk ferromagnetic aggregates, or permanent magnets, for high-performance applications.

The grant also will support graduate student fellowships in the lab.

Said Wiezorek: “Current methods of producing permanent magnets are expensive and energy-intensive, requiring imported rare-earth metals and high temperatures. By using a more affordable and less expensive magnesium aluminum alloy we can reduce a six-step manufacturing process into two stages and more efficiently and affordably produce permanent magnets for use in electro-generation.”

The research will explore the effective manufacture of rare-earth-metal-free magnetic materials, which are considered critical to technologies used in the conversion between mechanical work and electrical power, as well as in power transmission and distribution.

The improved manufacture of permanent magnet materials based on abundant ingredients can positively impact the development of sustainable energy technologies from turbine power generation to electric vehicle battery charging.

The machining-based process will deliver high-purity manganese-aluminum alloy-based micro-particulates with an internal ultrafine-grained structure at the nanoscale level. To determine the most effective process-structure-property relationships for the magnets, the team will use physics-based numerical models with magnetic and mechanical property measurements, X-ray diffraction and electron microscopy experiments.

Additionally, the researchers’ machining-based manufacturing is adaptable to a range of alloy systems and has the potential to advance the field of powder-particulate-based manufacturing of functional and structural material in general.

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The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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