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September 3, 2009

Research Notes

Pitt to lead gas well wastewater project

The U.S. Department of Energy recently selected Pitt as one of nine partners that will develop techniques for curtailing the possible environmental and health hazards associated with tapping the massive natural gas reserves lying beneath Pennsylvania and surrounding states.

Researchers in the Swanson School of Engineering will lead a three-year, $1.06 million project to better manage the wastewater generated by the extraction process used on the Marcellus Shale. The Marcellus Shale is mined using a technique called hydraulic fracturing in which a high-pressure mix of water, sand and chemicals known as “slicking agents” fractures the rock formation to allow trapped gas to escape.

The formation is estimated to contain some $500 billion in recoverable gas.

One gas well can consume 2 million to 5 million gallons of fluid, a portion of which returns to the surface as wastewater, or “flowback.” Flowback contains hydrocarbons, heavy metals, natural radioactive materials and dissolved solids such as calcium, potassium, sodium, chloride and carbonate.

Typically, the salty wastewater remains in reservoirs or the environment, but Pitt’s method would allow it to be reused in gas wells, containing costs, limiting byproducts that flow into the environment and reducing the strain on freshwater sources currently tapped during extraction.

In addition, the researchers seek to tackle the problem of acid mine drainage by using it as a sanitizer and supplemental water source.

“Our approach is to not only reuse the wastewater, but also reduce the level of treatment it requires prior to being reused, which should be a much more economical approach,” said Radisav Vidic, chair of the Department of Civil and Environmental Engineering and a William Kepler Whiteford professor. “And by reusing the acid mine drainage readily available at many gas drilling locations, we can manage acid mine drainage from older mines and wastewater from current drilling operations, both of which are serious environmental concerns.”

Vidic heads the project with Eric Beckman, co-director of Pitt’s Mascaro Center for Sustainable Innovation and the George M. Bevier professor of chemical and petroleum engineering. They will work with Carnegie Mellon University assistant professor Kelvin Gregory.

To contain flowback pollution and freshwater consumption, Vidic and Beckman will develop new slicking agents that would be stable in high-salinity water. These chemicals would allow the flowback to be reused in adjacent gas wells without extensive off-site purification. Then, they will study the use of locally available acid mine drainage to further treat the flowback and simultaneously supplement the freshwater supply. Finally, the cleaner flowback would be pumped back into the gas well, reducing the strain on freshwater sources and curtailing costs of shipping and storing wastewater.

The National Energy Technology Laboratory — the lead research and development office for the federal energy department’s Office of Fossil Energy — will contribute more than $794,000 to the effort, and Pitt will provide about $269,000.

Pitt was the only Pennsylvania institution granted a project.

More information on the projects is available at

Obesity linked to brain degeneration

Based on data gathered from brain scans conducted for the Pittsburgh-based Cardiovascular Health Study, researchers at Pitt and UCLA found that people age 70 or older and overweight with a body mass index (BMI) of 25-30 had 4 percent less tissue in the frontal lobes of the brain than their normal-weight peers.

Those who were obese with a BMI greater than 30 had 8 percent less tissue in the same regions, which are crucial for cognitive tasks such as memory and planning.

Lead investigator Cyrus A. Raji, a student in the School of Medicine’s combined MD/PhD program, said, “It seems that along with increased risk for health problems, such as type 2 diabetes and heart disease, obesity is bad for your brain. We have linked it to shrinkage of brain areas that also are targeted by Alzheimer’s. But that could mean exercising, eating right and keeping weight under control can maintain brain health with aging and potentially lower the risk for Alzheimer’s and other dementias.”

The 94 participants in the study, which was published this month in the online version of Human Brain Mapping, all were cognitively normal at the time their brain imaging was done and five years later. New methods of computer analysis were applied to the high-resolution scans, allowing three-dimensional mapping of brain structures to reveal patterns in volume differences that were not apparent in previous research.

The team found that the people defined as obese had lost brain tissue in the frontal and temporal lobes, areas of the brain critical for planning and memory, and in the anterior cingulate gyrus (attention and executive functions), hippocampus (long-term memory) and basal ganglia (movement). Overweight people showed brain loss in the basal ganglia, the corona radiata, white matter comprised of axons, and the parietal lobe (sensory lobe).

“This is the first time anyone has created brain maps proving the link between being overweight and severe brain degeneration,” said senior investigator Paul M. Thompson of UCLA School of Medicine. “The brains of obese people looked 16 years older than the brains of those who were lean, and the brains of overweight people looked eight years older.”

The research was funded by grants from the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, the National Center for Research Resources and the American Heart Association.

Co-authors include Oscar L. Lopez of neurology, James T. Becker of psychiatry and Lewis H. Kuller of the Graduate School of Public Health.

HSLS, SIS share librarianship grant

Pitt’s Health Sciences Library System and the School of Information Sciences have been awarded a grant from the Institute of Museum and Library Services (IMLS). The three-year grant, for $991,311, will support the development of a joint post-master’s degree certificate of advanced studies in health sciences librarianship.

The grant from IMLS will help fund curriculum development and evaluation, online course delivery infrastructure and student recruitment along with tuition scholarships for 27 students throughout the United States.

iHealth@Pitt will offer specialized preparation for professional positions in health sciences libraries. The program will include online coursework, an applied research project, mentoring experiences and attendance at a national conference.

Coursework will address such issues as evidence-based medicine, teaching and instruction in a health care setting, clinical librarianship, expert searching in medical resources and integration of information resources in electronic health records.

Students may enroll in the yearlong iHealth@Pitt program beginning in May 2010.

Obesity research funded

John Jakicic, chair of the Department of Health and Physical Activity, has received four grants to research obesity intervention.

Three studies start this month. One from the National Heart, Lung and Blood Institute is for $3 million over five years and examines intervention strategies to improve long-term weight loss in young adults 18-35 years of age. The focus is to include innovative technologies (such as text messaging and wearable technologies to provide real-time information on energy balance) in behavioral interventions across a 24-month intervention period.

The second study, funded by the National Institute of Aging for approximately $500,000 over five years, is an ancillary study to the multi-center Look AHEAD Study to examine changes in physical and cognitive function in overweight older adults with type 2 diabetes.

In a study funded by the National Institute for Digestive, Diabetes and Kidney Diseases (NIDDK) for two years as part of the NIH stimulus funding, metabolic parameters in type 2 diabetes randomized to bariatric surgery or a lifestyle intervention will be compared. Jakicic is a co-investigator with principal investigator Anita Courcoulas of the medical school’s Department of Surgery.

Jakicic also has received a grant funded by the NIDDK for approximately $100,000 as part of the NIH stimulus funding to develop an on-site exercise training facility to support obesity-related research at Pitt. This will include a full line of both cardiovascular and resistance training equipment that will be made available to researchers throughout the University community starting in early 2010.

Nursing grants announced

The School of Nursing recently announced the following grants to faculty members:

• Susan A. Albrecht, associate dean for student and alumni services, development and public relations and professor in the Department of Health and Community Systems, received a $59,275 grant from the U.S Department of Health and Human Services for a nurse faculty loan program. Albrecht also received an $8,547 award from the Pennsylvania Higher Education Assistance Agency for Dr. Edna B. McKenzie Scholarships for Disadvantaged Students.

• Helen Burns, associate dean for clinical education and professor in the Department of Health and Community Systems, received a grant award from the Pennsylvania Department of Labor and Industry for “Nursing Education Initiatives for Clinical Education.” Burns also received a $242,154 grant from the U.S. Department of Health and Human Services for “Nurse Education Practice and Retention.”

• Judith Callan, Department of Health and Community Systems, received a grant from Pitt’s Clinical and Translational Science Institute’s clinical research scholars program. The grant will support 75 percent of her salary and provide $25,000 in research funds through June 2011.

• Eileen Chasens, professor in the Department of Health and Community Systems and coordinator of the accelerated second degree BSN program, received a two-year $416,625 R21 award from the National Heart, Lung and Blood Institute for “OSA, Sleepiness and Activity in Diabetes Management.”

• JiYeon Choi, Department of Health Promotion and Development, received a $96,472 grant from the National Institute of Nursing Research for “Caregivers of Prolonged Mechanical Ventilation: Mind-Body Interaction Model.”

• Pei-Ying Chuang, Department of Acute and Tertiary Care, received a two-year grant of $9,804 from the Oncology Nursing Society for “Genetics, Psychological Stress and Cytokines in Oncology Caregivers.” The group also awarded Yvette Conley, professor in the Department of Health Promotion and Development, and Catherine Bender of the Department of Health and Community Systems a grant for their project entitled, “Genomics of Cognitive Function in Breast Cancer.”

• Willa Doswell, Department of Health Promotion and Development, received a grant of $55,277 over two years from the Staunton Farm Foundation for “Project Uplift: Using Parish Nurses to Reduce Mental and Behavioral Health Risk in Urban Communities.”

• Dean Jacqueline Dunbar-Jacob received a $100,000 grant from the Pennsylvania Higher Education Foundation for the school’s graduate nurse education grant program.

• Rick Henker, vice chair in the Department of Acute and Tertiary Care, received a $25,000 grant from the University’s Clinical and Translational Science Institute basic to clinical collaborative research pilot program for “Genetic & Other Risk Factors of Opioid-Induced Sedation and Respiratory Depression: Mice to Humans and Back Again.”

• Heeyoung Lee, Department of Health and Community Systems, received a $4,480 grant from the Sigma Theta Tau International Honor Society of Nursing for “Physical Activity in Young Adults With Early Stage Schizophrenia: A Pilot Study.”

• Margaret Rosenzweig, Department of Acute and Tertiary Care, received a grant of $1.241 million over five years from the American Cancer Society for “The ACTS Intervention to Reduce Breast Cancer Treatment Disparity.” Rosenzweig also received a $10,000 grant from the Oncology Nursing Society for “The SEA Intervention for Women With Metastatic Breast Cancer.”

• Karen Wickersham, Department of Health Promotion and Development, received an F31 award from the National Institute for Nursing Research for “A Study of Medication Taking for NSCLC Patients Receiving Oral Targeted Therapy.” The award, funded for three years, is valued at $123,528.

Hookah smoking among college athletes studied

College students who participate in intramural or club sports are less likely to smoke cigarettes than non-athletes, but are more likely than non-athletes to smoke from a hookah, according to a Pitt study that appears online in the Journal of Adolescent Health.

“This study demonstrates that many athletes clearly perceive hookah smoking as less of a concern than cigarette smoking,” said Brian Primack, professor of medicine and pediatrics at the School of Medicine and lead author of the study. “What they don’t realize, however, is that they are exposing themselves to many of the same toxic chemicals contained in cigarettes.”

Pitt researchers examined data from 8,745 college-age individuals who participated in the National College Health Assessment administered by the American College Health Association in 2008, and found that 33 percent of the respondents reported participating in varsity, club and intramural sport in the preceding 12 months. Overall, 29.5 percent of the total sample reported having smoked from a hookah.

Consistent with what has been reported in the past, all types of athletes were less likely than non-athletes to smoke cigarettes. Similarly, varsity athletes were 22 percent less likely than non-athletes to have smoked tobacco from a hookah.

However, club and intramural participants were 15 percent more likely than non-athletes to have smoked tobacco from a hookah.

Pitt co-authors of the study were Carl Fertman of the Department of Health and Physical Activity, Kristen Rice of the Center for Research on Health Care and Michael Fine of medicine.

Primack’s research was supported by the Robert Wood Johnson Foundation, the National Cancer Institute and the Maurice Falk Foundation.

Inflammation, insulin resistance linked

An exploration of the molecular links between insulin resistance and inflammation may have revealed a novel target for diabetes treatment, say scientists at Children’s Hospital’s John G. Rangos Sr. Research Center. Their findings appeared in the online version of Diabetes, one of the journals of the American Diabetes Association.

Senior author and pediatrics professor H. Henry Dong said signs of low-grade systemic inflammation are not uncommon among people who have the pre-diabetic condition known as metabolic syndrome, as well as in animal models of obesity and type 2, or insulin-resistant, diabetes, but it is not yet clear if there is a cause-and-effect relationship between chronic exposure to low-grade inflammation and the onset of insulin resistance. “Other studies have shown that in patients who have inflammation and diabetes, insulin-sensitizing drugs seem to reduce inflammation while anti-inflammatory therapies improve sensitivity to insulin,” he said.

Dong’s team examined the role played by a protein called Forkhead Box 01 (Fox01), which his previous research showed contributes to elevations in triglycerides in an animal model of obesity and diabetes.

In the current paper, the researchers found in cultured cells and mouse experiments that Fox01 stimulates inflammatory white blood cells called macrophages, which migrate to the liver and fat tissue in insulin-resistant states to increase production of a cytokine called interleukin-1 beta (IL-1B). The cytokine in turn interferes with insulin signaling. Insulin typically inhibits Fox01, setting up a feedback loop in healthy tissues that helps regulate insulin levels.

“The findings suggest that when there is a lack of insulin or when cells such as macrophages are resistant to its presence, there are no brakes on Fox01’s stimulation of IL-1B and its further interference with insulin signaling,” Dong said. “That might explain why chronic inflammation often is coupled with obesity and type 2 diabetes. Also, a drug that acts on Fox01 might be able to better control blood sugar.”

Co-authors of the paper include lead author Dongming Su, Gina Coudriet, Dae Hyun Kim, German Perdermo, Shen Qu, Sandra Slusher, Hubert Tse, Jon Piganelli and Nick Giannoukakis, all of the hospital pediatrics department’s Division of Immunogenetics and the School of Medicine, and Yi Lu and Jian Zhang of the Division of Hematology and Oncology in the medical school’s Department of Medicine.

The study was funded by the American Diabetes Association and the National Institutes of Health

Protein shapes studied

Computational biologists at the School of Medicine have shown that proteins need to change shape as part of their biological activity. The shape changes also allow the small molecules that are attracted to a given protein to select the structure that permits the best binding.

The findings, which could help in drug discovery and in designing compounds with the most impact on protein function, were published this week in the online version of the Proceedings of the National Academy of Sciences.

According to the classical view, known as “induced fit,” drug binding causes a change in the target protein structure, said senior author Ivet Bahar, John K. Vries Chair of the Department of Computational Biology. But it now appears that a protein has many different conformations that are already available even without the presence of a binding molecule, or ligand.

Gathering information about the array of conformations a target protein might exhibit can be of great use when designing new drugs, enabling the scientist to better identify the structural pocket into which the drug must fit to cause significant alterations in protein function, such as the inhibition of an enzyme reaction, Bahar said.

For the study, Bahar and doctoral student Ahmet Bakan focused on three common drug targets, namely enzymes important in HIV, inflammatory response and the cell division cycle.

Using the sets of conformations of protein-ligand complexes stored in the Protein Data Bank, an information repository at Rutgers University, researchers figured out what structures the enzymes had both alone and when bound to a variety of small molecules.

“It seems there are simple but robust rules that control ligand binding,” Bahar explained. “If we know the rules, we can make better predictions about which binding sites to target to make more effective drugs.”

Bahar’s research is funded by the National Institutes of Health

Nanoscale devices developed

Two nanoscale devices recently reported by Pitt researchers in two separate journals harness the potential of carbon nanomaterials in one case to enhance technologies for drug or imaging agent delivery and energy storage systems, and in another to bolster the sensitivity of oxygen sensors essential in confined settings.

In a report published online by Advanced Materials Aug. 12, a team led by chemistry professors Alexander Star and Stéphane Petoud described the creation of nanosized capsules that are universally compatible with a range of substances, particularly related to medicine and energy. When applied to medicine, the tiny vessels potentially can carry anticancer drugs or medical-imaging agents and be steered via antibodies and biological molecules to specific locations within the human body. Energy applications include the storage of lithium and hydrogen in batteries and fuel cells.

Pitt graduate chemistry student Brett Allen was the paper’s lead author. The project included chemistry graduate student Chad Shade and Adrienne Yingling, now a graduate of Pitt’s PhD chemistry program.

In a separate paper that appeared online Aug. 16 in Nature Chemistry, another team headed by Star and Petoud revealed the development of a highly sensitive fluorescent oxygen sensor that can detect minute amounts of the gas. Oxygen detectors are important safety devices in mines, aircraft, submarines and other confined spaces, the researchers noted. The sensor consists of carbon nanotubes coated with a luminescent compound incorporating europium, a reactive metal found in fluorescent bulbs, television/computer screens and lasers, among other applications.

The researchers gauged oxygen levels by measuring the intensity of its glow when exposed to ultraviolent light and the tubes’ change in electrical conductance. The tubes demonstrated sensitivity to oxygen concentrations as low as 5 percent (normal atmospheric concentration is around 20 percent) and were unaffected by other atmospheric gases such as carbon dioxide and nitrogen. The team calculated that the sensor can indicate a level as low as 0.4 percent.

The second paper was authored by Shade and chemistry graduate students Douglas Kauffman and Hyounsoo Uh.

EPA pesticide tests too short?

The four-day testing period the U.S. Environmental Protection Agency (EPA) commonly uses to determine safe levels of pesticide exposure for humans and animals could fail to account for the toxins’ long-term effects, Pitt researchers reported in the September edition of Environmental Toxicology and Chemistry.

The team found that the highly toxic pesticide endosulfan — a neurotoxin banned in several nations but still used extensively in U.S. agriculture — can exhibit a “lag effect” with the fallout from exposure not surfacing until after direct contact has ended.

Lead author Devin Jones, a recent Pitt biological sciences graduate, conducted the experiment under biological sciences professor Rick Relyea, with collaboration from Pitt post-doctoral researcher John Hammond. The paper is available at

The team exposed nine species of frog and toad tadpoles to endosulfan levels “expected and found in nature” for the EPA’s required four-day period, then moved the tadpoles to clean water for an additional four days, Jones reported. Although endosulfan ultimately was toxic to all species, three species of tadpole showed no significant sensitivity to the chemical until after they were transferred to fresh water. Within four days of being moved, up to 97 percent of leopard frog tadpoles perished along with up to 50 percent of spring peeper and American toad tadpoles.

Tadpoles in the Pitt project spent four days in 0.5 liters of water containing endosulfan concentrations of 2, 6, 7, 35, 60, and 296 parts-per-billion (ppb), levels consistent with those found in nature. The team cites estimates from Australia, where endosulfan is widely used, that the pesticide can reach 700 ppb when sprayed as close as 10 meters from the ponds amphibians typically call home and 4 ppb when sprayed within 200 meters. The EPA estimates that surface drinking water can have chronic endosulfan levels of 0.5 to 1.5 ppb and acute concentrations of 4.5 to 23.9 ppb.

Leopard frogs, spring peepers and American toads fared well during the experiment’s first four days, but once they were in clean water, the death rate spiked for animals previously exposed to 35 and 60 ppb. Although the other six species did not experience the lag effect, the initial doses of endosulfan still were devastating at very low concentrations. Grey and Pacific tree frogs, Western toads and Cascades frogs began dying in large numbers from doses as low as 7 ppb, while the same amount killed all green frog and bullfrog tadpoles.

Of most concern, explained Relyea, is that tadpoles and other amphibians are sensitive to pollutants and considered an environmental indicator species. The EPA does not require testing on amphibians to determine pesticide safety, but Relyea previously found that endosulfan is 1,000 times more lethal to amphibians than other pesticides. Yet, he said, if the powerful insecticide cannot kill one of the world’s most susceptible species in four days, then the four-day test period may not gauge adequately the long-term effects on larger, less-sensitive species.

“When a pesticide’s toxic effect takes more than four days to appear, it raises serious concerns about making regulatory decisions based on standard four-day tests for any organism,” Relyea said. “For most pesticides, we assume that animals will die during the period of exposure, but we do not expect substantial death after the exposure has ended. Even if EPA regulations required testing on amphibians, our research demonstrates that the standard four-day toxicity test would have dramatically underestimated the lethal impact of endosulfan on even this notably sensitive species.”

The endosulfan findings build on a 10-year effort by Relyea to understand the potential links between the global decline in amphibians, routine pesticide use and the possible threat to humans in the future.

A second paper by Relyea and Jones also in the current Environmental Toxicology and Chemistry expanded on one of Relyea’s most notable investigations, a series of findings published in Ecological Applications in 2005 indicating that the popular weed-killer Roundup is “extremely lethal” to amphibians in concentrations found in the environment. The latest work determined the toxicity of Roundup Original Max for a wider group of larval amphibians, including nine frog and toad species and four salamander species. The report is available at


Poli sci prof to evaluate USAID program

Political science professor Scott Morgenstern has received a $685,000 grant from Higher Education for Development funded by the U.S. Agency for International Development (USAID) to update and evaluate USAID’s work in supporting political party development worldwide.

As part of its overall goal of building democracy in countries throughout the world, USAID began in 1991 to fund programs aimed at strengthening political parties. Morgenstern and his research team will evaluate USAID programs by conducting eight-12 case studies in selected countries to assess how well they achieved their goals.

The team will develop a conceptual framework for party and party system development, examine party and party system requirements under different situations and evaluate the effectiveness of USAID programs. The goal is to help guide future USAID political party programs by providing them with an analytical tool to determine needs and evaluate programs.

Cancer vaccine target found

Pitt researchers have found that some healthy people naturally have developed an immune response against a protein that is produced in high levels in many cancers, including breast, lung and head and neck cancers. The finding suggests that a vaccine against the protein could prevent malignancies in high-risk individuals.

Mice that were vaccinated to boost their immune response against this cell cycle protein, called cyclin B1, were able to reject a tumor challenge in which they were exposed to a cancer cell line that overproduced it, said senior author Olivera Finn, Distinguished Professor and chair of the Department of Immunology at the School of Medicine. The results were reported in the Proceedings of the National Academy of Sciences.

“Cyclin B1 is known to be produced in excess amounts in several kinds of cancer,” she said. “While we were studying it, we noted that many healthy people already had an immune response, or antibodies, against the protein, even though they’d never had cancer.”

According to the researchers, the immune response most likely developed during a childhood viral infection, when inflammatory responses are strong. Cells infected with chicken pox virus, for example, look very much like tumor cells because they, too, overproduce cyclin B1. The virus actually packages the host protein, which ultimately gets shown to the immune system as a marker of infected cells that must be destroyed.

“Because cyclin B1 is a ‘self’ protein, there have been concerns that boosting the immune response against it would produce autoimmunity and create new problems,” Finn said. “But now that we know that perhaps 20 to 30 percent of people already recognize it as abnormal when made in excess, we can be more confident about the safety of a vaccine strategy to immunize high-risk groups against it.”

She is working with collaborators to open, by the end of the year, a clinical trial of a cyclin B1 treatment vaccine in lung cancer patients, and she plans to assess it in the future as a prevention strategy in patients with pre-malignant lung lesions.

Natural immunity to other tumor-specific proteins has been found before, Finn noted. Her team developed a vaccine to boost response against MUC1, a protein that is produced abnormally in colon cancer and in precancerous polyps. The MUC1 colon cancer prevention vaccine is being tested in a clinical trial led by colleagues at UPMC.

“In previous work, we found that women who developed an immune response to MUC1, typically after pelvic surgery, mumps or mastitis, have a much lower risk for ovarian cancer,” Finn said. “Cyclin B1 and MUC1 are part of a big family of self-proteins that become over-produced during cancer development, so they have great potential as targets in prevention vaccines.”

Other Pitt authors of the paper were Laura Vella and Min Yu of the Department of Immunology.

The research was funded by the National Cancer Institute and the Dana Foundation.


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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