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September 30, 2010

Research Notes

Sustainable LCA criteria to be updated

Melissa Bilec, a faculty member in civil and environmental engineering in the Swanson School of Engineering, has received a $2 million emerging frontiers in research and innovation grant in science in energy and environmental design from the National Science Foundation to lead a group of Pitt and Carnegie Mellon University researchers in evaluating and expanding the scope of life-cycle assessments, or LCAs.

When used in construction, LCAs analyze a building’s environmental impact throughout its existence, from the production of its basic components and raw materials to its eventual demolition and disposal.

The current LCA model has not developed in step with sustainable engineering research, Bilec explained, meaning that important considerations are not factored into a building’s construction. Notably absent is a method for quantifying a structure’s potential effect on the people who use it every day, she said. For instance, LCAs currently consider the emissions produced when carpeting is manufactured, but not the gases slowly released by the carpeting and its adhesives over time.

Bilec said: “For our study, we first want to make sure sustainable buildings perform as they should. If they do not, we need to modify the design. Our second goal concerns the human aspect. We spend 90 percent of our time inside, and we know very little about the real quality of indoor air. The interaction between people and the indoor environment needs to be considered if we want to understand overall sustainability.”

To improve the LCA model, the researchers will first identify its weakest components — those that need to be more thorough, considerations that are overlooked and cumbersome aspects of the model — through electronic surveys distributed to people and trade groups in the architecture, construction and engineering fields, as well as an evaluation of current case studies on sustainable building.

The team then will develop criteria that engineers and architects can use to determine the long-term sustainability of a building and its components. In addition, the group plans to integrate the revised LCA template into a digital interface. This simulator would predict the possible environmental footprint of various construction decisions. Bilec said the group then would test the interface on structures in Pittsburgh.

The final prospective step in the project is to incorporate the new LCA into the building information modeling process, real-time software widely used to design and construct buildings.

Co-investigators from Pitt include Alex Jones of electrical and computer engineering, Amy Landis of civil and environmental engineering and Laura Schaefer of mechanical engineering and materials science.

Cardiolipin linked to pneumonia severity

A structural molecule and the cellular pump that regulates its levels influence the severity of pneumonia and could provide new ways of treating the lung infection, according to scientists at Pitt and the University of Iowa. Their findings are available online in Nature Medicine.

Despite decades of research, there has been little new information on which biological mechanisms make bacterial pneumonia get worse, said senior author Rama K. Mallampalli, a faculty member in the School of Medicine’s Acute Lung Injury Center of Excellence and pulmonary division chief at the VA Pittsburgh Healthcare System.

“Our study reveals some of the molecular steps that can lead to lung injury after infection and shows us new avenues for pneumonia therapy that don’t have to target bacteria, as antibiotics do,” he said.

The researchers found that lung fluid from humans and mice with pneumonia contains abnormally high levels of cardiolipin, a structural molecule that typically is found in the membranes of energy-making mitochondria. A carrier protein called Atp8b1 transports the molecule from the lung fluid into the cell, acting as a pump that regulates cardiolipin levels.

Infection leads to the death of cells, and that releases cellular components, including cardiolipin, into the surrounding fluid, Mallampalli explained. The carrier protein can become overwhelmed, allowing cardiolipin levels to climb. The excess cardiolipin disrupts the function of surfactant, a lubricant that is necessary for the proper expansion and contraction of the lungs during breathing, which can lead to more tissue damage.

When cardiolipin was administered to mice, their lung function became impaired and their lung tissue became damaged akin to what is seen with pneumonia. Similarly, mice with a mutation in the carrier protein gene were more likely to have severe pneumonia.

“This research was inspired by the knowledge that some people have a mutation in this protein, a condition called Byler’s disease, and they are more likely to get pneumonia,” Mallampalli noted.

In other experiments, mice with the gene mutation and pneumonia were treated with an engineered protein fragment that attached to the cardiolipin binding site, preventing the molecule from interacting with surfactant and ultimately reducing lung injury and improving survival.

“A similar strategy might work in people and could be a very useful option at a time when we have bacterial strains that are resistant to multiple antibiotics,” said Mark Gladwin, chief of the Division of Pulmonary, Allergy and Critical Care Medicine.

Mallampalli and his colleagues now are working on ways to deliver proteins into the lung that tightly bind cardiolipin, with the goal of translating this approach for testing in pneumonia patients.

The study team includes Bill B. Chen and Bryan J. McVerry of the Acute Lung Injury Center of Excellence.

The research was funded by the U.S. Department of Veterans Affairs and the National Institutes of Health.

Valve implants aid emphysema patients

Tiny one-way valves that block portions of emphysema-ravaged lungs improved lung function, exercise tolerance and symptoms at the cost of a modest increase in adverse events, according to a multicenter international study led by School of Medicine researchers. The findings are available in the Sept. 23 issue of the New England Journal of Medicine.

The valves are designed to allow emptying but not re-inflation of overinflated portions of the lung, making them shrink and allowing the healthier portions of the lung to function more normally. The valves are about the size of a pencil eraser and are inserted using a bronchoscope. They are being tested as a minimally invasive substitute for lung-reduction surgery, which involves removing selected areas of hyperinflated lungs.

The Endobronchial Valve for Emphysema Palliation Trial (VENT) compared the safety and efficacy of endobronchial valves (EBV) to medical treatment in patients with severe emphysema, explained principal investigator Frank C. Sciurba, a faculty member in medicine and director of the Emphysema/COPD Research Center in the Division of Pulmonary, Allergy and Critical Care Medicine.

“This study confirmed that a minimally invasive alternative to lung reduction surgery can result in significant improvements in well-selected patients. Lessons learned in this study will allow us to better select patients who are most likely to benefit from the procedure.”

Of 321 participants enrolled in the study, 220 were randomized to receive EBV. Standard tests of lung function showed measurable improvements among participants who received the valves. At 12 months, there was no difference in survival rates, but valve patients reported feeling better. Adverse events included pneumonia, respiratory failure, coughing up blood and air leaking from the treated lung, and were mild relative to the possible complications of lung surgery.

While the valves currently are available clinically only in Europe, more clinical trials in the United States are anticipated. The next trials will utilize lessons learned in the VENT study, which revealed that patients with the most heterogeneous emphysema (differences in severity between lobes of the lung) and who had complete fissures between lobes (preventing the non-blocked lung from filling the blocked lung back up with air) have much better results.

Sciurba is supported by the National Institutes of Health. The study was supported by Emphasys Medical and Pulmonx.

Nursing faculty receive funding

The School of Nursing recently announced research funding awarded to the following faculty members:

• Michael Beach of the Department of Acute and Tertiary Care was awarded $60,000 from the Robert Wood Johnson Foundation new careers in nursing scholarship program. The initiative aims to expand the pipeline of students in accelerated baccalaureate nursing programs.

• Catherine M. Bender of the Department of Health and Community Systems received a $1.1 million grant from the National Institute of Nursing Research for training nurse scientists to lead independent research programs in cancer survivorship.

• Mary Beth Happ of the Department of Acute and Tertiary Care received a $50,000 grant from the Greenwall Foundation’s Kornfeld program on bioethics and patient care. Her research involves nonspeaking patients in the intensive care unit and explores the ethical implications of their participation in treatment decisions.

• Elizabeth A. Schlenk of the Department of Health and Community Systems received a $2 million grant from the National Institutes of Health for research on promoting physical activity in older adults with co-morbidities.

UPB student support service funds renewed

The U.S. Department of Education has awarded $238,491 to Pitt-Bradford for student support services through Aug. 31, 2011. The award is expected to continue for a total of five years, totaling $1.1 million.

The program provides academic help and other services to low-income, first-generation or disabled college students. Staff work with participants to design an individualized academic plan for each student.

The grant will be used to provide services to 160 students per year. Those services include financial aid information, graduate and professional school counseling, personal coaching, self-paced computer tutorials, study-skills workshops and others. In 2008-09, 55 percent of Pitt-Bradford students met the eligibility requirements for the program.

To date, 67 UPB students served by the program have earned their first bachelor’s degree, 14 have earned an associate degree and 12 have entered graduate school or returned to receive teaching certificates.

Better preschools benefit low-income kids later

A longitudinal study led by psychology faculty member Elizabeth Votruba-Drzal reveals that children from low-income families placed in high-quality preschool programs have fewer behavioral problems in middle childhood, and that such settings were especially important for boys and black children.

The study, conducted by researchers at Pitt, Boston College, Universidad de los Andes, Loyola University Chicago and Northwestern University, was published in the September/October issue of the journal Child Development.

The researchers looked at approximately 350 children from low-income families in Boston, Chicago and San Antonio when they were preschoolers, ages 2-4, and again when they reached middle childhood, ages 7-11.

The youngsters were part of the Three-City Study, a long-term look at the well-being of low-income families following welfare reform in 1996. The children in the study used the child care options available in their communities.

An examination of the data revealed that children who attended more responsive, stimulating and well-structured settings during preschool had fewer behavioral problems — such as aggression and rule breaking — in middle childhood. Boys and black children especially seemed to be responsive to stimulating and responsive care outside the home.

“This study adds to a growing body of evidence suggesting the need for policy and programmatic efforts to increase low-income families’ access to high-quality early care and education,” said Votruba-Drzal.

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Office of the Assistant Secretary of Planning, the Administration on Developmental Disabilities, the Administration for Children and Families, the Social Security Administration and the National Institute of Mental Health.

Anti-HIV drug film being developed

With the support of an $11.8 million, five-year federal grant, Pitt researchers and their collaborators are developing a quick-dissolving vaginal film containing a powerful drug that reduces the risk of HIV infection, and they plan to begin testing it locally within a year.

A small film, like those used to deliver breath fresheners, could have several advantages over vaginal microbicide gels that currently are being tested overseas, said Sharon Hillier, faculty member in obstetrics, gynecology and reproductive sciences at the School of Medicine, senior investigator at Magee-Womens Research Institute (MWRI) and co-principal investigator of the new project, which is funded by the National Institute of Allergy and Infectious Diseases.

“Multiple films could be packaged in discrete cartridges without the need for refrigeration, making them portable and easier to store and distribute, and therefore probably cheaper than a gel,” she noted. “And, because they aren’t likely to be as messy as a gel, women might be willing to use them routinely, perhaps on a daily basis.”

Led by co-principal investigator Lisa Cencia Rohan, School of Pharmacy faculty member and MWRI associate investigator, the researchers first will develop a film version of the anti-retroviral drug tenofovir and establish the necessary processes to make it on a large scale for human use.

Tenofovir in its pill form is used as an HIV treatment, and South African researchers recently showed that a gel formulation of the drug cut the risk of HIV infection by more than half among women who were most conscientious about applying it before and after intercourse; the gel reduced the infection risk by 39 percent among women who were less vigilant.

The film would provide an alternative dosage form that preclinical testing suggests could release the drug faster and more efficiently than the gel version.

“An effective microbicide strategy should include different forms of the product,” Rohan said. “Women will have preferences, and having options to meet those needs will lead to greater use and therefore better protection from infection.”

The researchers also will develop and test a second film containing another anti-HIV agent that has yet to be determined.

Pitt project collaborators include Bernard J. Moncla and Charlene Dezzutti, both of obstetrics, gynecology and reproductive sciences and MWRI. Also involved are researchers from the University of Washington, the New York State Institute for Basic Research, Johns Hopkins and the Eastern Virginia Medical School.

Fat stem cells OK to rebuild breasts

Fat-derived stem cells can be used to aid reconstruction of breast tissue after mastectomy as long as there is no evidence of active cancer, according to researchers at the School of Medicine. Their findings are available in Tissue Engineering Part A.

For some time plastic surgeons have moved fat from one part of the body into the breasts for reconstruction, but with some complications and a varying success rate, explained surgery faculty member and senior author Vera S. Donnenberg. More recently, they have considered adding stem cells derived from adipose, or fat, tissue (ADSC) or the bone marrow to the transferred fat with the aim of supporting graft integration by enhancing new blood vessel formation.

“But it has not been clear whether these stem cells are safe for breast cancer patients because they could send growth signals that promote tumor reactivation or provide new blood vessels for the tumor,” Donnenberg said. “Our research suggests that this risk is real if the patient still has active tumor cells, but is safe when the cells are inactive or resting.”

For the study, the researchers collected adipose tissue that would have been discarded during “tummy tuck” procedures performed by study co-author J. Peter Rubin of the Department of Surgery, whose team has several federally funded projects underway to develop fat grafting and stem cell therapies for reconstruction of a variety of tissues.

The  researchers  isolated  ADSC from normal fat and mixed them with human breast cancer cells obtained directly from patients. After two weeks in culture they found that ADSC greatly encouraged the growth of tumor cells. In a follow-up experiment, the researchers injected small numbers of highly purified active or resting tumor cells under the skin of mice either with ADSC or with previously irradiated tumor cells. The combination of active tumor cells and ADSC led to dramatic tumor growth, while injections of resting tumor cells were not affected by co-injection of either ADSC or irradiated tumor cells.

“There is already some clinical evidence that breast reconstruction with transplanted fat is safe,” Donnenberg said.  “Our findings lead us to conclude that augmentation of fat grafts with additional ADSC should be postponed until there is no evidence of active cancer. Our data in the mouse suggest that dormant cancer cells are not sensitive to the growth signals sent by the ADSC.”

Co-authors included Ludovic Zimmerlin and Albert D. Donnenberg of medicine; Per Basse, immunology, and Rodney J. Landreneau, surgery.

The study was funded by grants from the U.S. Department of Defense, the National Institutes of Health, the Hillman Foundation, the University of Pittsburgh Cancer Institute, the Glimmer of Hope Foundation and the Commonwealth of Pennsylvania through the McGowan Institute for Regenerative Medicine.

NSF awards grants to info science

The National Science Foundation (NSF) recently awarded five grants to School of Information Sciences (iSchool) faculty.

• Geoffrey Bowker, with co-principal investigator Dean Ronald L. Larsen, secured a grant for $90,684 to support a workshop on “Emerging Configurations of the Virtual and the Real” this fall. Funded by NSF’s Office of Cyberinfrastructure, the event will bring together experts from various fields to address the impact of advances in information and communications technologies (as well as the resulting human disengagement with the natural world) on research and education in the information sciences. The intent is to outline the intellectual frontiers of research across the iSchools, and to create synergies for future research efforts.

• Peter Brusilovsky is the recipient of two EAGER (Early Concept Grants for Exploratory Research) awards. The first grant for $99,999, for which Jung Sun Oh will serve as co-PI, will support a project exploring personalization and social networking for short-term communities. Using academic research conferences as a test bed, Brusilovsky will explore new methods to leverage information about user interests (available from multiple external resources) and develop techniques to facilitate use of existing social technologies.

Brusilovsky’s second EAGER grant, for $155,882, will look at how to model and visualize latent communities — people who form communities based on their similar interests. This work will consider how to elicit latent communities from various kinds of data about individuals available on the modern social web and deliver the results in a manner suitable for interactive exploration through interactive visualizations. This will be one of the first attempts to use a variety of social web data and approaches for community modeling.

• Daqing He received a $49,983 grant from NSF’s Division of Information & Intelligent Systems to explore the emerging phenomenon of public academic information resources on the social web. The project aims to develop an assessment and association identification framework for online academic information to facilitate researchers in accessing, organizing, utilizing and exchanging all types of academic information.

• Cory Knobel and Geoffrey Bowker were awarded a grant from NSF’s Office of Cyberinfrastructure to study “Evaluating Best Practices in Collaborative Cyber-Science and Engineering.”

The project, funded at $198,506, will result in a socio-technically informed set of outcome-based best practices and evaluation criteria for large-scale cyber-science efforts. The goal is to create a framework to transform cyber-enabled grand challenge communities, improve the ability to identify and assess categories of project impact across levels of scale and guide the future development of appropriate cyberinfrastructure tools.

Anti-radiation grant renewed

Researchers at the University of Pittsburgh Cancer Institute and the School of Medicine have been awarded $13.9 million over five years by the National Institute of Allergy and Infectious Diseases (NIAID) to continue developing small molecule radiation protectors and mitigators that can be easily accessed and administered in the event of a large-scale radiological or nuclear emergency.

In 2005, NIAID’s Center for Countermeasures Against Radiation program granted $10 million over five years to Joel Greenberger, chair of the Department of Radiation Oncology, and his team of researchers in the University’s Center for Medical Countermeasures Against Radiation.

“With our previous funding, we dedicated our time to exploring the mitochondria — the energy generator of all cells — and developing drugs that could counteract damage caused by radiation exposure,” said Greenberger. “We proved that targeting small molecules to the mitochondria was a successful approach. With our current funding, we hope to accomplish a variety of goals, including gene identification for targeted therapies, finding a new approach to the development of radiation mitigators and developing strategies to deliver the drugs quickly and intelligently to block mitochondria ‘wrong-doings’ that could lead to massive cell death after a nuclear event.”

Previous funding supported research examining several potent mitigators of radiation damage, including new classes of chemicals and known natural compounds. Greenberger’s team, in conjunction with a team of chemists led by Peter Wipf, Distinguished Professor of Chemistry, aided in the development of JP4-039, a drug that assists the mitochondria in combating irradiation-induced cell death.

In addition, research from Greenberger’s lab showed resveratrol, the natural antioxidant commonly found in red wine and many plants, when altered by a process called acetylation protected mouse cells from radiation.

Other co-principal investigators on the study were Valerian Kagan, Detcho Stoyanovsky and Oleskandr Kapralov of environmental and occupational health; John Lazo, pharmacology and chemical biology; Hulya Bayir, critical care medicine; Song Li and Xiang Gao, pharmaceutical science; Paul Floreancig and Alexander Star of chemistry, and Hong Wang and Michael Epperly of radiation oncology.


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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