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August 29, 2013

Research Notes

Prof recognized for lung cancer work

School of Medicine faculty member and University of Pittsburgh Cancer Institute researcher Timothy Burns has been recognized for his lung cancer work with the American Lung Association (ALA) Lung Cancer Discovery Award and the LUNGevity Career Development Award, totaling $500,000 over three years.

Lung cancer is the leading cause of cancer death worldwide. Recent advances in the treatment of lung cancer have come from the recognition that lung cancer is not a single disease, but rather a collection of distinct cancers driven by cancer genes, called oncogenes, that cause the tumors to grow.

Said Burns: “This knowledge has led to the development of targeted therapies for a small percentage of patients, and we think this approach has great promise in our push for personalized medicine.” He will receive $200,000 over two years for research to develop novel therapies for patients with certain oncogene-dependent lung cancers.

Surgery prof earns career development award

Surgery faculty member Daolin Tang was awarded a 2013 Pancreatic Cancer Action Network-American Association for Cancer Research career development award.

The two-year grant supports junior faculty to conduct pancreatic cancer research and establish successful career paths in this field.

Prof’s paper is Science editor’s choice

A research article by Judy Yang, Nickolas A. DeCecco Chemical Engineering Professor in the Swanson School of Engineering, was selected as an editor’s choice in the Aug. 9 issue of Science. Her article, “Non-Crystalline-to-Crystalline Transformations in Pt Nanoparticles,” appeared in the July 19 edition of the Journal of the American Chemical Society.

With her team, Yang studied the structure of platinum nanoparticles using a combination of mathematical equations, microscopes and X-rays. After examining more than 3,000 nanoparticles, she distinguished between non-crystalline and crystalline nanoparticles, finding that no single size marked the transition between the two. Yang noted that transformational properties of nanoparticles could be useful in a variety of technological platforms.

NSF funds clean energy tech research

Although catalysts have been integral to chemistry and chemical engineering for more than a century, the atomic processes behind catalytic reactions are little understood. A National Science Foundation (NSF) grant will allow Pitt researchers to collaborate with the State University of New York-Binghamton and Brookhaven National Laboratory to use the newest nano-characterization tools to understand how catalysis occurs and how it can enable cleaner energy technologies while reducing the creation of harmful by-products.

The study is funded through a $459,697 grant from NSF’s Chemical, Bioengineering, Environmental and Transport Systems (CBET) division. It will be led by principal investigator Judy Yang and co-PI Götz Veser, both Nickolas A. DeCecco Professors of Chemical and Petroleum Engineering at the Swanson school.

The research group will focus on copper catalysts, which are more abundant and affordable than other materials and are used for numerous processes including methanol production. They will study the copper catalysts at reaction conditions during methanol partial oxidation.

In addition, the grant will fund graduate student research and impact future academic and outreach programs both at Pitt and Binghamton.

Physics profs get grants

Pitt researchers were among the Pennsylvania recipients of new grant funding from The Charles E. Kaufman Foundation (of The Pittsburgh Foundation) for research in chemistry, biology and physics.

A two-year, $242,310 “New Initiative” grant was awarded to Sergey M. Frolov and W. Vincent Liu of the Dietrich school Department of Physics and Astronomy for research on “Topological Quantum Wire Emulators.”

Biotechnology faculty member Graham Hatfull is chair of the Kaufman foundation’s scientific advisory board.

Prof wins cardiovascular science award

Lewis Kuller, emeritus faculty member in the Graduate School of Public Health, has received the 2013 Population Prize from the American Heart Association (AHA). This annual prize recognizes outstanding contributions to the advancement of cardiovascular science.

Prof named NIH geriatric reviewer

Epidemiology faculty member Caterina Rosano was appointed to the aging systems and geriatric study section of the Center for Scientific Review of the National Institutes of Health (NIH). Through June 2017, Rosano will review biomedical research grant applications submitted to the NIH, make recommendations on these applications to the appropriate NIH national advisory council or board and survey the status of research in the geriatric field.

Lupus award honors immunology prof

Immunology faculty member Mark J. Shlomchik in the School of Medicine was the first recipient of the Lupus Insight Prize of $200,000 for innovative research on lupus, an autoimmune disorder affecting 1.5 million Americans. The award is given jointly by the Alliance for Lupus Research, the Lupus Foundation of America and the Lupus Research Institute. It honors an investigator whose research has a high likelihood of generating further advances in understanding the causes, biology, treatments or cure of lupus.

Help sought here for dengue fever vaccine

Researchers are expanding their efforts to develop a vaccine for a deadly tropical virus by calling for local volunteers.

Dengue fever, a mosquito-borne illness that is contracted by as many as 100 million people worldwide annually, has re-emerged in the United States and is endemic in Puerto Rico, spurring increased demand for a vaccine. To aid that effort, researchers are putting out the call for Pittsburghers who have spent time in tropical areas to give a small blood sample.

Study participants’ identities will be kept anonymous, and they will be compensated for their time. For more information, contact Diana Campbell, Emily Frost or Paolo Piazza, Department of Infectious Diseases and Microbiology, at 8-2940, or email

NSF grant may fuel improved solar cell manufacturing

Swanson school faculty members Paul W. Leu, industrial engineering, and Kevin P. Chen, electrical and computer engineering, were awarded $107,498 to develop a process for the scalable laser manufacturing of more efficient solar cells.

Said Leu, principal investigator: “We’re exploring new structures, called photonic crystals, that are at the wavelength scale or smaller to better trap light within the absorbing region of the solar cell. As demonstrated in nature with the colors you see in the morpho butterfly wing or peacock feather, these structures can control how light is reflected and absorbed. We’re developing new laser technologies to scalably manufacture these 3-D nanostructures into low-cost and efficient solar cells. These structures are so small that a solar cell will have about a trillion of them.”

This research will provide new understanding of how light interacts with different materials and develop new scalable processes for manufacturing nanostructures. Ultimately, the researchers hope this work will help bring solar cells to more residential houses, solar farms and small villages around the world.

Med profs regenerate mouse heart

For the first time, a mouse heart was able to contract and beat again after its own cells were stripped and replaced with human heart precursor cells, School of Medicine faculty reported in the current issue of Nature Communications. The research shows the promise that regenerating a functional organ by placing human-induced pluripotent stem cells — which could be personalized for the recipient — in a three-dimensional scaffold could have for transplantation, drug testing models and understanding heart development.

In the U.S., one person dies of heart disease every 34 seconds, and more than 5 million people suffer from heart failure, meaning a reduced ability to pump blood, said senior investigator Lei Yang, developmental biology faculty member. More than half of heart disease patients do not respond to current therapies and there is a scarcity of donor organs.

For the project, the research team first “decellularized,” or removed all the cells, from a mouse heart, a process that takes about 10 hours using a variety of agents. They then repopulated the remaining heart framework, or scaffold, with multipotential cardiovascular progenitor (MCP) cells.

“Nobody has tried using these MCPs for heart regeneration before,” said Yang. “It turns out that the heart’s extracellular matrix — the material that is the substrate of heart scaffold — can send signals to guide the MCPs into becoming the specialized cells that are needed for proper heart function.”

After a few weeks, the mouse heart not only had been rebuilt with human cells, it also began contracting again, at the rate of 40-50 beats per minute, the researchers found. More work must be done to make the heart contract strongly enough to be able to pump blood effectively, and to rebuild the heart’s electrical conduction system correctly so that the heart rate speeds up and slows down appropriately.

“One of our next goals is to see if it’s feasible to make a patch of human heart muscle,” Yang said. “We could use patches to replace a region damaged by a heart attack. That might be easier to achieve because it won’t require as many cells as a whole human-sized organ would.”

Co-authors included Tung-Ying Lu, Bo Lin and Kimimasa Tobita, all of Yang’s department; Jong Kim and Guy Salama of the UPMC Heart and Vascular Institute, and Mara Sullivan of the University’s Center for Biologic Imaging.

The project was funded by Pitt, the AHA and the National Science Council (Taiwan).

NSF grant aids in multiphase materials study

Multiphase materials are ubiquitous in everyday life, from rubber tires and paints to mayonnaise and shampoo. These materials are distinctive in that some are solid particles dispersed in fluid, some are mixtures of two fluids and some are gas bubbles dispersed in fluids. An NSF grant will allow Swanson school rsearchers to better understand and control the structure and flow of such three-component multiphase systems with the goal of improving manufacturing processes and potentially leading to the creation of new materials.

The project is funded through a $311,689 grant from NSF’s Chemical, Bioengineering, Environmental and Transport Systems Division, through the particulate and multiphase processes program.

The overall goal is to examine the role of surface tension-related phenomena (often called capillarity) in multiphase flow and structure. Said principal investigator Sachin Velankar, chemical and petroleum engineering faculty member: “We know a great deal about structure and flow of particulate suspensions as well as droplet-matrix emulsions. But we know very little about what happens when all three things — particles, fluid drops and a continuous phase fluid — are present. We know that the flow behavior in materials is not quite solid, and not quite liquid, but we know little about the structure. The eventual goal of the project is to develop new ways to process multiphase materials as well as create new materials that are not possible at present.”

Program invests $400,000 in med tech

The Wallace H. Coulter translational research partners II program will fund efforts to fight infection post-surgery with an antibiotic gel; develop a meniscus implant for temporomandibular joint (TMJ) patients; treat an overactive bladder through foot stimulation, and attack skin cancer with a microneedle bandage.

The Coulter program, a campus-wide effort led by the Swanson school, identifies, selects, funds and mentors translational research by clinician-bioengineer teams that address unmet clinical needs through innovative technologies.

Teams competing for Coulter program funding are required to participate with Pitt MBA and law school students in a four-month From Benchtop to Bedside course. This course is designed to teach researchers how to develop key deliverables such as a business model, business plan, product development plan and investment pitch necessary to assess the clinical and commercial potential of each technology.

The 2013 funded projects were:

• TheraGel: Prevent Infection of Implanted Devices Bioengineering, by Yadong Wang, bioengineering, and David Schwartzman, medicine.

• MatriDisc: An Inductive, Scaffold-Based Device for Reconstruction of the TMJ Meniscus Bioengineering, by Bryan N. Brown, bioengineering; Alejandro J. Almarza, oral biology and bioengineering, and William L. Chung, oral and maxillofacial surgery.

• FootStim Bioengineering, by Changfeng Tai, urology and bioengineering, and Mang Chen, urology.

• Skinject PatchIT Bioengineering, by Louis Falo, dermatology and bioengineering, and Larisa Geskin, dermatology.

Smallest terahertz detector invented

Molecules soon could be “scanned” in a fashion similar to imaging screenings at airports, thanks to a detector developed by physicists.

The detector, featured in a recent issue of Nano Letters, may have the ability to chemically identify single molecules using terahertz radiation, a range of light far below what the eye can detect.

Said study co-author Jeremy Levy, physics and astronomy faculty member in the Dietrich school: “Our invention allows lines to be ‘written’ and ‘erased’ much in the manner that an Etch A Sketch toy operates. The only difference is that the smallest feature is a trillion times smaller than the children’s toy, able to create conductive lines as narrow as two nanometers.”

Terahertz radiation is useful for identifying specific types of molecules. This type of radiation is generated and detected with the help of an ultrafast laser, a strobe light that turns on and off in less than 30 quadrillionths of a second. Terahertz imaging commonly is used in airport scanners, but has been hard to apply to individual molecules due to a lack of sources and detectors at those scales.

“We believe it would be possible to isolate and probe single nanostructures and even molecules performing terahertz spectroscopy at the ultimate level of a single molecule,” said Levy. “Such resolution will be unprecedented and could be useful for fundamental studies as well as more practical applications.”

The study also involved researchers from Levy’s department: Patrick Irvin, Yanjun Ma and Mengchen Huang, and from the University of Wisconsin-Madison. It was supported by grants from the U.S. Air Force Office of Scientific Research and NSF.

Motor cortex grows efficient with practice

Not only does practice make perfect, it also makes for more efficient generation of neuronal activity in the primary motor cortex, the area of the brain that plans and executes movement, according to researchers from the School of Medicine. Their findings, published online in Nature Neuroscience, showed that practice leads to decreased metabolic activity for internally generated movements, but not for visually guided motor tasks, and suggest the motor cortex is “plastic” and a potential site for the storage of motor skills.

The team, led by senior investigator Peter L. Strick, neurobiology chair, found that the hand area of the primary motor cortex is known to be larger among professional pianists than in amateur ones. This observation has suggested that extensive practice and the development of expert performance induces changes in the primary motor cortex.

Prior imaging studies have shown that markers of synaptic activity -— the input signals to neurons — decrease in the primary motor cortex as repeated actions become routine and an individual develops expertise at a motor skill. The researchers found that markers of synaptic activity also display a decrease in monkeys trained to perform sequences of movements that are guided from memory — an internally generated task — rather than from vision. They wondered whether the change in synaptic activity indicated that neuron firing also declined.

To examine this issue they recorded neuron activity and sampled metabolic activity, a measure of synaptic activity in the same animals. All the monkeys were trained on two tasks and were rewarded when they reached out to touch an object in front of them. In the visually guided task, a visual target showed the monkeys where to reach and the end point was switched randomly from trial to trial. In the internally generated task, the monkeys were trained to perform short sequences of movements without visual cues. They practiced the sequences until they achieved a skill level comparable to an expert typist.

The researchers found neuron activity was comparable between monkeys that performed visually guided and internally generated tasks. However, metabolic activity was high for the visually guided task, but only modest during the internally generated task.

Said Strick: “This tells us that practicing a skilled movement and the development of expertise leads to more efficient generation of neuron activity in the primary motor cortex to produce the movement. The increase in efficiency could be created by a number of factors such as more effective synapses, greater synchrony in inputs and more finely tuned inputs. What is really important is that our results indicate that practice changes the primary motor cortex so that it can become an important substrate for the storage of motor skills. Thus, the motor cortex is adaptable, or plastic.”

Co-authors of the paper were neurobiology faculty member Nathalie Picard and a researcher from Tohoku University, Japan.

The study was funded by the U.S. Department of Veterans Affairs and NIH.

Targeting “cell sleep” lowers cancer recurrence

An international research team led by University of Pittsburgh Cancer Institute (UPCI) scientists discovered that preventing cancer cells from entering a state of cellular sleep lets cancer drugs work more effectively, lowering the chance of cancer recurrence.

The findings, published in Cancer Research, are the first to show that it is possible to therapeutically target cancer cells to keep them from entering a cellular state called quiescence, or “cell sleep.” Quiescence can be a dangerous source of tumor recurrence because cancer drugs typically don’t destroy quiescent cells.

Said Anette Duensing, pathology faculty member at UPCI: “By inhibiting a key regulator of quiescence, we are able to kill a larger fraction of cancer cells.”

Duensing and her colleagues made the discovery while studying gastrointestinal stromal tumors (GISTs). According to the American Cancer Society, about 5,000 GISTs occur each year in the United States, with an estimated five-year survival rate of 45 percent in patients with advanced disease.

GISTs are caused by a single gene mutation, which means they can be successfully treated with the targeted therapy drug imatinib, or Gleevec. Unlike traditional chemotherapy, which kills all rapidly dividing cells, targeted therapy stops cancer by interfering with specific molecules needed for tumor growth.

Unfortunately, GISTs rapidly develop resistance to the treatment and complete cancer remission using Gleevec is rare.

A key regulator of the cancer cell sleep process is a protein complex called DREAM, which is named for the proteins involved. Gleevec induces cell sleep using the DREAM complex, which means that the drug intrinsically limits its own effectiveness.

“When we disrupted the DREAM complex in the lab, we significantly increased cancer cell death using Gleevec,” said Duensing. “This underscores the importance of the DREAM complex as a novel drug target worthy of preclinical and clinical investigations.”

The study was a collaboration with the Dana-Farber Cancer Institute, the Catholic University in Belgium and the University of Heidelberg in Germany. UPCI co-authors were Sergei Boichuk, Joshua A. Parry, Kathleen R. Makielski, Julianne L. Baron, James P. Zewe, Keith R. Mehalek and Danushka S. Seneviratne.

This research was supported by the American Cancer Society, the GIST Cancer Research Fund, The Life Raft Group and private donations.

Light moves and molds gels

Some animals, such as the octopus and cuttlefish, transform their shape based on environment, fending off attackers or threats in the wild. Researchers have worked toward mimicking similar biological responses in non-living organisms, as it would have significant implications in the medical arena.

Now researchers, including lead author Anna Balazs, chemical and petroleum engineering faculty member in the Swanson school, have demonstrated such a biomimetic response using hydrogels, a material that constitutes most contact lenses and microfluidic or fluid-controlled technologies. Their study, published in Advanced Functional Materials, shows that these gels can be both reconfigured and controlled by light, undergoing self-sustained motion — a uniquely biomimetic behavior.

Said Balazs: “Imagine an apartment with a particular arrangement of rooms all in one location. Now, consider the possibility of being able to shine a particular configuration of lights on this structure and thereby completely changing not only the entire layout, but also the location of the apartment. This is what we’ve demonstrated with hydrogels.”

Together with departmental colleague Olga Kuksenok, Balazs experimented with a newer type of hydrogel containing spirobenzopyran molecules. Such materials had been shown to form distinct 2-D patterns on initially flat surfaces when introduced to varying displays of light and are hydrophilic (“liking” water) in the dark but become hydrophobic (“disliking” water) under blue light. Therefore, Balazs and Kuksenok anticipated that light could be a useful stimulus for tailoring the gel’s shape.

Using computer modeling, the Pitt team demonstrated that the gels “ran away” when exposed to the light, exhibiting direct, sustained motion. The team also factored in heat, combining the light and local variations in temperature to further control the samples’ motions. Controlling a material with light and temperature could be applicable, Balazs said, for regulating the movement of a microscopic “conveyor belt” or “elevator” in a microfluidic device, which could be appropriate for optical applications.

The team also demonstrated that the gels could undergo dynamic reconfiguration, meaning that with a different combination of lights, the gel could be used for another purpose. Reconfigurable systems are useful because they are reusable, leading to a significant reduction in cost. Such processes could have a dramatic effect on manufacturing and sustainability, since the same sample could be used and reused for multiple applications.

Funding was provided by the U.S. Department of Energy.

Premature aging affects kids’ arthritis

The joints of children with the most common form of chronic inflammatory arthritis contain immune cells that resemble those of 90-year-olds, according to a study led by researchers at the School of Medicine. The findings, published in the August issue of Arthritis and Rheumatism, suggest that innovative treatment approaches could aim to prevent premature aging of immune cells.

According to senior researcher Abbe de Vallejo, faculty member in pediatrics and immunology, juvenile idiopathic arthritis, or JIA, is the most prevalent rheumatic condition in the world and affects one of every 1,000 children in the U.S. It usually starts with a swollen ankle, knee or wrist that parents assume is due to a minor injury sustained while playing.

“Untreated JIA has devastating consequences,” said de Vallejo. “It can slow growth and, in extreme cases, the child can be physically disfigured. It’s a degenerative disease that eats up the joints.”

Doctors have long thought of JIA as an autoimmune disease, but previous studies by de Vallejo of young adults with rheumatoid arthritis indicated that a certain population of cells present in the joint synovial fluid and blood displayed signs of abnormal cell division and premature aging. His current team at Children’s Hospital wanted to see if that was true in pediatric arthritis.

They examined T-cells in the synovial fluid and blood from 98 children ages 1-17 with JIA, as well as 46 blood samples from children who didn’t have the disease. T-cells are the army of immune cells that eradicate infection, tumors and other dangerous agents to which people may be exposed.

The research team found about one-third of the T-cells of children with JIA had shortened telomeres and had reduced, or in some cases lost, the capacity to proliferate. Telomeres are the ends of chromosomes that don’t code for proteins and, because they are not fully copied by enzyme mechanisms, are trimmed slightly during each DNA replication cycle. It is thought that aging occurs when the telomeres become too short for DNA replication and cell division to proceed normally.

“The T-cells of the children with JIA had very short telomeres, about the length we see in a 90-year-old,” said de Vallejo. “Those same T-cells express unusually high levels of several classic protein markers of cell aging and exhaustion. These kids haven’t lived long enough to have cells that look that old. This is the first indication that premature aging is occurring in this childhood condition.”

In addition, the T-cells had become dysregulated, and their immune activity could be stimulated through atypical cell surface receptors. More must be learned about the unusual cells and about genetic mechanisms that might contribute to the development of JIA, de Vallejo said, but these findings could point the way to new therapies


“JIA is typically treated with broad-spectrum drugs such as steroids and biologics that essentially paralyze the entire immune system, but only a third of the cells are affected and their abnormality seems to be premature aging, rather than autoimmune activity,” he noted. “This study suggests cell-targeted treatments could be developed to prevent this premature immune aging.”

Co-authors included other researchers from the School of Medicine, UPMC and the Mayo Clinic.

The project was funded by the Nancy E. Taylor Foundation for Chronic Diseases, the Arthritis Foundation and NIH.

New sky survey dataset has 60,000 stars

Astronomers with the Sloan Digital Sky Survey III (SDSS-III) have released “Data Release 10,” a new online public dataset featuring 60,000 stars that are helping to tell the story of how the Milky Way galaxy formed.

Data Release 10 is a new set of high-resolution stellar spectra — measurements of the amount of light given off by a star at each wavelength — using infrared light that is invisible to human eyes but able to penetrate the veil of dust that obscures the center of the galaxy. These new spectra are the first data released by the SDSS-III’s Apache Point Observatory Galactic Evolution Experiment (APOGEE), an effort to create a comprehensive census of the Milky Way galaxy.

Said SDSS-III spokesperson Michael Wood-Vasey, faculty member in physics and astronomy: “Public access to data has always been a key goal of our project.”

To accomplish its goal of observing 100,000 stars in three years, the APOGEE instrument observed up to 300 different stars at a time using fiber-optic cables plugged into a large aluminum plate with holes drilled to line up with each star. Light passes through each fiber into the APOGEE spectrograph, where a prism-like grating distributes the light by wavelength. The grating is the first and largest of its kind deployed in an astronomy instrument.

The data provide a rich context for investigating questions about the stars themselves. Because APOGEE observes each target star several times, it can identify changes in each star’s spectrum over time. This feature has enabled the APOGEE team to discover unusual types of rapidly variable stars, to pinpoint how many stars are actually binary stars with unseen companions and even to detect the subtle stellar motions caused by orbiting exoplanets.

Data Release 10 also publishes another 685,000 spectra from the SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS). These new spectra come from galaxies and quasars as seen when the universe was much younger, just as the mysterious force of dark energy was beginning to influence the universe’s expansion. The new BOSS spectra, and the additional spectra that the SDSS-III will continue to obtain in the final years of the survey, will help scientists in their quest to understand what dark energy might be.

The new data have the potential not only to revolutionize understanding of the Milky Way, but also to make a major impact on public understanding of science. Data from Data Release 10 are available online at

Diets lacking omega-3s lead to worsening effects over generations

Diets lacking omega-3 fatty acids, found in foods like wild fish, eggs and grass-fed livestock, can have worsening effects over consecutive generations, especially affecting teens, according to a study under lead author Bita Moghaddam, neuroscience faculty member in the Dietrich school.

The researchers found that in a rodent model second-generation deficiencies of omega-3s caused elevated states of anxiety and hyperactivity in adolescents and affected memory and cognition.

Said Moghaddam: “We have always assumed that stress at this age is the main environmental insult that contributes to developing these conditions in at-risk individuals but this study indicates that nutrition is a big factor, too. We found that this dietary deficiency can compromise the behavioral health of adolescents, not only because their diet is deficient but because their parents’ diet was deficient as well. This is of particular concern because adolescence is a very vulnerable time for developing psychiatric disorders, including schizophrenia and addiction.”

Performing experiments in rats in Moghaddam’s laboratory, the research team examined a second generation of omega-3-deficient diets, mimicking present-day adolescents. Parents of many of today’s teens were born in the 1960s and 1970s, a time period in which omega-3-deficient oils like corn and soy oil became prevalent, and farm animals moved from eating grass to grain. Since omega-3s are present in grass and algae, much of today’s grain-fed cattle contain less of these essential fatty acids.

The team administered a set of behavioral tasks to study the learning and memory, decision-making, anxiety and hyperactivity of both adults and adolescents. Although subjects appeared to be in general good physical health, there were behavioral deficiencies in adolescents that were more pronounced in second-generation subjects with omega-3 deficiencies. Overall, these adolescents were more anxious and hyperactive, learned at a slower rate, and had impaired problem-solving abilities.

“Our study shows that, while the omega-3 deficiency influences the behavior of both adults and adolescents, the nature of this influence is different between the age groups,” said Moghaddam. “We observed changes in areas of the brain responsible for decision making and habit formation.”

The team now is exploring epigenetics as a potential cause. This is a process in which environmental events influence genetic information. Likewise, the team is exploring markers of inflammation in the brain since omega-3 deficiencies cause an increase of omega-6 fats, which are proinflammatory molecules in the brain and other tissues.

Other researchers included neurobiology faculty member Gonzalo Torres and, from the Moghaddam laboratory, postdoctoral fellow Corina Bondi; laboratory technician Jody Tock and Nelson Totah, now a postdoctoral fellow at Max Planck Institute for Biological Cybernetics. The team also included NIH researchers.

The study was supported by grants from NIH and the National Institute on Aging intramural research program, and was published in Biological Psychiatry.

Self-evaluation of menopausal symptoms underestimates burden

Physicians should consider a more in-depth evaluation of their menopausal patients’ symptoms, as current approaches might not accurately reflect the number of hot flashes and night sweats each woman experiences, a new School of Medicine study has found. The study was led by Rebecca Thurston, faculty member in psychiatry and epidemiology and director of the Women’s Biobehavioral Health Laboratory.

Patients tend to underestimate how often they have hot flashes and night sweats, clinically known as vasomotor symptoms (VMS), particularly if they suffer from anxiety, and overestimate nighttime VMS if they experience sleep disturbances, according to the study published in the journal Menopause.

New studies designed to treat VMS rely on patients reporting their symptoms, so improving accuracy directly impacts patient care.

Said Thurston: “We think physicians may want to consider probing deeper when evaluating their menopausal patients, to determine if anxiety or sleep problems might be influencing the way they perceive their VMS. Typically, we use end-of-the-day and morning diaries to measure VMS, but these may not be the best approaches to testing how well our treatments reduce VMS, particularly if the treatments impact anxiety or sleep.”

Thurston’s study evaluated three different types of VMS reporting. Women were asked to either record their symptoms at the end of each day and in the morning upon waking, or to report their symptoms at the time of VMS occurrence. At the same time, their symptoms were monitored via a portable hot flash monitor worn around the waist that continuously measures skin conductance, a validated biological measure of hot flashes.

Women’s VMS reporting errors, Thurston noted, “are important because accurate measurement of VMS is instrumental to adequately testing treatment options. While very common in menopausal women, hot flashes and night sweats can disrupt a woman’s quality of life significantly.”

The study was part of the Study of Women’s Health Across the Nation (SWAN), a multisite, multiethnic, longitudinal study that aims to characterize biological and psychosocial changes during the menopausal transition.

NIH funds pediatric TBI study

The Graduate School of Public Health and Children’s Hospital have been selected by NIH to lead a $16.5 million international study to evaluate treatments for pediatric traumatic brain injuries (TBI). The five-year study is headed by Stephen Wisniewski, public health’s senior associate dean, epidemiology faculty member and co-director of the Epidemiology Data Center, and Michael J. Bell, critical care medicine and neurological surgery faculty in medicine and director of Pediatric Neurocritical Care and Neurotrauma at Children’s.

The study aims to provide evidence to change clinical practices and provide recommendations for guidelines that could improve outcomes for injured children.

Researchers plan to enroll 1,000 children up to 18 years old from more than 36 locations in the United States and abroad to compare the effectiveness of immediate TBI treatments, including strategies to lower intracranial pressure, strategies to treat secondary injuries and the delivery of nutrients.

Said Bell: “Incremental improvement in outcomes of traumatic brain injury could make enormous differences for the health of children, but such advances have remained elusive. ”

The study, which is expected to more than double existing evidence-based treatment recommendations, will provide volumes of data for improved TBI research protocols that would limit variability in treatments. Such variability has led to the failure of previous randomized controlled trials.

The study also will evaluate the effectiveness of six therapies encompassing three specific aims:  intracranial hypertension therapies; secondary insult prevention, and metabolism.

Children with TBIs, where an intracranial pressure monitor is placed, will be enrolled in the study. The children will receive the standard care offered by their hospital and extensive data on their cases will be collected over the week following the injury. Outcomes will be tested at six months and one year after injury.

Other investigators on the project include Patrick M. Kochanek, critical care medicine, anesthesiology, pediatrics and clinical and translational science, and Sue Beers, psychiatry, and others from institutions in Phoenix, Toronto, Boston and Washington, as well as NIH and Carnegie Mellon University. Epidemiologists on the project are Tony Fabio and Sheryl Kelsey of public health.

Graphite’s attraction to water skewed in previous finding

Objects made from graphite — such as lithium-ion batteries — are “hydrophobic,” meaning that they “dislike” water, and for decades this lack of likeability has presented significant challenges for building more durable technological devices made with graphite.

Now it appears that past samples of graphite were contaminated by air, causing the samples to appear hydrophobic, according to research led by Lei Li, chemical and petroleum engineering faculty in the Swanson school, and Haitao Liu, chemistry faculty member in the Dietrich school.

Their team has demonstrated that these materials actually are intrinsically attracted to water or “hydrophilic.” The findings, published in Nature Materials, have particular implications for lithium-ion batteries and super capacitors, as both battery types are built from these materials.

Said Li: “These findings hold implications for producing stronger, more durable batteries. And, hopefully, it will also be important to the fabrication of devices in various nanotechnology areas.”

Former undergraduate engineering student Rebecca McGinley noticed the inconsistent results regarding the surface’s “wetting behavior,” or its reaction to water, pushing the team to further investigate the strange phenomena. They found that, when graphite and graphene are exposed to air, a thin layer of hydrocarbon (a compound made entirely of hydrogen and carbon) quickly contaminated the surface. Using infrared spectroscopy and X-ray photoelectron spectroscopy, the team was able to “see” this hydrocarbon layer, noting its hydrophobic nature. However, when the team used heat to remove this contaminant layer, the surface became hydrophilic.

Said Liu: “Plastic and other types of materials emit hydrocarbon into the air. And this hasn’t been a factor in past sample experiments. In the past, the research community believed that graphite didn’t ‘like’ water, possibly because their samples were always contaminated; the contamination happens typically within 10 minutes.”

Liu and Li say this wettability could have an impact on how much energy can be stored within such devices that use lithium-ion batteries or super capacitors. The team will conduct follow-up studies to understand the origins of their observations and study how controlling this wettability may impact some of the applications of graphite (e.g. lubrication and energy storage).

In addition to McGinley, collaborators from Li’s engineering laboratory included former engineering students Patrick Ireland, Andrew Kozbial, Yongjin Wang and current undergraduate student Brittni Morganstein. From Liu’s chemistry laboratory, graduate students Zhiting Li and Feng Zhou were involved as well as former undergraduate student Ganesh Shenoy and current chemistry student Alyssa Kunkle. Postdoctoral researcher in chemistry Sumedh Surwade assisted.

The paper appeared online July 21 and was supported by the Mascaro Center for Sustainable Innovation and the Central Research Development Fund, Taiho Kogyo Tribology Research Foundation, the Air Force Office of Scientific Research, the Office of Naval Research and NSF.

Biomed informatics prof wins two NIH grants

Michael M. Wagner, faculty member in biomedical informatics, has received two grants from NIH.

The National Institute of General Medical Sciences (NIGMS) has funded a study with several aims. These include:

• developing a standard vocabulary for the field of epidemic modeling using a tool called Protégé;

• developing a standard syntax using the vocabulary for representing the inputs (such as disease control measures) and outputs of epidemic models and using this syntax in an existing system, called the Apollo Web Service, that makes it possible for other computer programs to access epidemic models, and

• increasing the capacity to run epidemic models on supercomputers to demonstrate the value of the work of the first three aims.

The National Library of Medicine-funded study will further develop and evaluate a probabilistic approach to disease surveillance. A probabilistic case detection system (CDS) will compute the likelihoods of patient findings for each of a set of infectious diseases for every patient in a monitored population. CDS computes these likelihoods from data in electronic medical records.

Wagner already has used this method to evaluate influenza; it now will be extended to six additional respiratory infectious diseases. The proposed approach has the potential to improve the information available to public health officials and physicians, which can be expected to improve clinical and public health decision making and ultimately to improve population health.

NIH supports early lung cancer detection

Biomedical informatics faculty member Vanathi Gopalakrishnan has received an NIH grant from NIGMS for a project to develop computational methods for integrative biomarker discovery from related but separate data sets produced by predictive molecular profiling studies of disease.

This will generate new experimental data for early detection of lung cancer, and has the potential to help create new diagnostic screening tools for this disease, which is a leading cause of death from cancer in the United States.

Electronic med records: Aid or distraction?

The Electronic Medical Record (EMR) has the potential to improve quality of care but, to date, there has been little research to quantify the effect of EMR as either a barrier or facilitator of quality.

In an ideal, patient-centered examination process, the health-care provider would focus primarily on the patient. However, in the time-constrained framework of office consultations, the EMR competes for the provider’s attention.

Biomedical informatics faculty member Harry Hochheiser, using funds from the Agency for Healthcare Research and Quality, will study the degree to which EMR task complexity imposes a cognitive burden on providers, and will use this understanding to improve workflows and free physicians to focus on patient interactions.

To do this, Hochheiser will collect a variety of data on physician EMR use, including screen capture, eye-tracking, video and subjective responses to build models of physician workflow and suggest alternative designs.

HPV vaccine lags in black women

Even with access to health care, African-American women are less likely to receive the human papillomavirus (HPV) vaccine, which reduces the risk for cervical cancer, according to a School of Medicine study published in the Journal of Adolescent Health. It suggests a need for health-care providers both to bolster HPV vaccination recommendations and address negative attitudes toward the vaccine among this vulnerable patient population.

HPV is a sexually transmitted infection that accounts for virtually all cervical cancer diagnoses. According to the Centers for Disease Control and Prevention, roughly 12,000 new cases of HPV-associated cervical cancer are diagnosed in the United States each year. Within the past decade, two HPV vaccines have been made available to adolescents and young adults aged 11-26 to reduce the risk of infection. The vaccine is administered in a three-step process and can cost more than $400 without health insurance.

Said Sonya Borrero, faculty member in medicine and senior author of the study: “The HPV vaccine is a first line of defense to protect against cervical cancer. Given that cervical cancer is more common and associated with higher mortality in African-American and Hispanic women than in white women, it is especially important to understand the barriers to HPV vaccination for these populations.”

Borrero and her fellow researchers used data from the 2006-10 National Survey of Family Growth, a nationwide cross-sectional survey administered by the U.S. Department of Health and Human Services, to examine the effect of race and ethnicity on HPV vaccine initiation in adolescent girls and young women and to determine whether access to health care influences this relationship.

In this sample of 2,168 females aged 15-24, African Americans were significantly less likely than whites to have initiated HPV vaccination (18.2 percent vs. 33.1 percent respectively). That disparity persisted even after taking into account sociodemographic factors and access to health care. Observed disparities in HPV vaccination for Hispanics, on the other hand, were largely explained by sociodemographic and health-care access variables, the researchers found.

“Our findings in African Americans suggest that there are other unmeasured patient- or provider-level factors contributing to under-vaccination and that alternate strategies need to be identified to increase HPV vaccination among African Americans,” said Borrero. “Further efforts are needed to understand how to overcome the patient-, parent- and provider-level barriers that hamper widespread uptake for this effective and safe vaccine.”

Although the data are limited, negative attitudes towards the HPV vaccine may be one critical barrier. African Americans also are less likely than their white counterparts to receive an HPV vaccine recommendation from a health-care provider. Some studies have shown higher vaccine initiation rates among adolescents from racial and ethnic minorities, Borrero noted, but this might be the result of different survey methods or reflect changes in patterns of HPV vaccination over time.

Co-authors from medicine included Elizabeth Miller, Amanda Gelman, Eleanor Bimla Schwarz, Aletha Y. Akers, and Kwonho Jeong. The project was funded by NIH.

NIH funds two grants for pharmacy prof

Song Li, faculty member in the School of Pharmacy, has received two NIH grants.

Prostate cancer is a significant health concern for men worldwide, but few treatment options are available to men with hormone-refractory prostate cancer (HRPC). Paclitaxel (PTX) is a key component of many therapeutic regimens for HRPC. However, the therapeutic potential of PTX is limited by its toxicity. In addition, drug resistance eventually may occur in most of the treated patients.

The first grant, “Nanomicellar Formation for Synergistic Targeting of Prostate Cancer,” aims to develop a strategy that can simultaneously improve selective delivery of PTX to tumor cells and sensitize the cancer cells to PTX, which is likely to significantly improve the outcome of the treatment.

Li recently has developed a novel delivery system that is based on a kind of embelin, which has been shown to possess antidiabetic, anti-inflammatory and hepatoprotective qualities.

Embelin also shows antitumor activity in various types of cancers largely through blocking the activity of X-linked inhibitor of apoptosis protein. XIAP is overexpressed in various types of cancer cells, particularly drug-resistant cancer cells, and inhibition of XIAP has been explored as a new approach for the treatment of cancers.

Li also will investigate whether the delivery system can be further improved.

Successful completion of this study could lead to the development of a novel therapy to advance the treatment of prostate cancer.

Li also has received funding from NIH for a study titled “Rational Design of Lipidic Vectors for Mitochondria-Targeted Antioxidants.”

Drug discovery is a costly and inefficient process. Many promising drugs identified from initial screening often are excluded from further investigation due to their poor water solubility and/or low bioavailability.

Incorporating drug formulation expertise early in the drug discovery process represents an important strategy to facilitate preclinical and clinical evaluations of promising candidates that are poorly water soluble.

Successful completion of this study could lead to the development of a new strategy that will facilitate the in-vivo application of many therapeutics that are poorly water soluble and difficult to formulate with existing lipidic systems.


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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