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March 7, 2013

Research Notes

1st high-speed quantum computer comes closer

A physics and astronomy faculty member has discovered a new method that better preserves the units necessary to power lightning-fast electronics, known as quantum bits or qubits. Hole spins, rather than electron spins, can keep quantum bits in the same physical state up to 10 times longer than before, according to Sergey Frolov of the Dietrich School of Arts and Sciences, who worked with researchers at Delft University of Technology in the Netherlands.

Said Frolov: “Previously, our group and others have used electron spins, but the problem was that they interacted with spins of nuclei, and therefore it was difficult to preserve the alignment and control of electron spins.”

Whereas normal computing bits hold mathematical values of zero or one, qubits live in a hazy superposition of both states. It is this quality, said Frolov, that allows them to perform multiple calculations at once, offering exponential speed over classical computers. However, maintaining the qubit’s state long enough to perform computation remains a longstanding challenge for physicists.

“To create a viable quantum computer, the demonstration of long-lived quantum bits, or qubits, is necessary,” he said. “With our work, we have gotten one step closer.”

The holes within hole spins literally are the empty spaces left when electrons are taken out. Using extremely thin filaments called InSb (indium antimonide) nanowires, the researchers created a transistor-like device that could transform the electrons into holes. They then precisely placed one hole in a nanoscale box called “a quantum dot” and controlled the spin of that hole using electric fields. This approach — featuring nanoscale size and a higher density of devices on an electronic chip — is far more advantageous than magnetic control, which has been typically employed until now, said Frolov.

“Our research shows that holes, or empty spaces, can make better spin qubits than electrons for future quantum computers.

“Spins are the smallest magnets in our universe,” he added. “Our vision for a quantum computer is to connect thousands of spins, and now we know how to control a single spin. In the future, we’d like to scale up this concept to include multiple qubits.”

Coauthors of the paper included faculty from Eindhoven University of Technology in the Netherlands.

Appearing in the Feb. 17 Nature Nanotechnology online, the study was supported by the Dutch Organization for Fundamental Research on Matter, the Netherlands Organization for Scientific Research and the European Research Council.

Transportation tops local concerns

Although Pittsburgh is at or near the top of numerous quality-of-life rankings, transportation remains a key concern for the region until a stable funding solution is found, according to a report released Feb. 24 by PittsburghTODAY, a regional indicators program in the University Center for Social and Urban Research (UCSUR).

Pittsburgh Today & Tomorrow 2013 draws a comprehensive profile of how Pittsburgh is faring compared with 14 other benchmark regions nationwide in 11 key quality-of-life categories: the arts, demographics, the economy, education, the environment, government, health, housing, public safety, sustainability and transportation. The other benchmark regions are Baltimore, Boston, Charlotte, Cincinnati, Cleveland, Denver, Detroit, Indianapolis, Kansas City, Milwaukee, Minneapolis-St. Paul, Philadelphia, Richmond and St. Louis.

While most of the news is positive, there are several areas of concern for the region in addition to transportation, according to the report: the environment, government, health and building sustainable communities.

Said Douglas Heuck, director of PittsburghTODAY: “We get behind the numbers through interviews with regional leaders in a broad range of sectors who weigh in on the key challenges and opportunities facing Pittsburgh.”

The report’s key conclusions include:

• Arts: Groups and organizations are finding ways to flourish despite challenging economic times. The seven-county Pittsburgh Metropolitan Statistical Area (MSA) is home to 486 arts and cultural organizations.

• Demographics: The region is getting decidedly younger. The population  of  20-34  year  olds grew by 7 percent over the past five years and is expected to grow another 8 percent by 2020.

• Economy: Pittsburgh is one of the most affordable places to live for moderate-income families. It’s also one of only three U.S. cities that have recovered from the recession that began in 2007.

• Education: The region remains among the nation’s leaders in terms of the percentage of the population that has a high school degree, its equivalent, or better. Graduation rates have improved or stayed the same in 70 percent of schools in the area.

• Environment: The air is the cleanest it has been since the Industrial Revolution, but a chronic sewage overflow problem continues to plague the region’s streams and rivers.

• Government: The region currently has an overabundance of governments, making consolidation a popular topic. People residing in the seven-county Pittsburgh MSA are ruled by more than 900 distinct government entities.

• Health: Despite the region’s broad health care network, it has higher-than-average rates of diabetes, obesity and deaths from cardiac arrest. Pittsburgh also ranks poorly in health-related behaviors, with comparatively low levels of physical activity and high rates of smoking.

• Housing: The area remains in the midst of a solid housing recovery, and the appreciation of home values in the region is the envy of most of the benchmark regions. Third-quarter home prices appreciated 5.8 percent from 2007 to 2012.

• Public Safety: Few regions can boast lower crime rates than Pittsburgh, as burglaries and thefts have declined steadily since 2006.

• Sustainability: Social equity is key to sustainable communities, and Pittsburgh has work to do. Sharp racial disparities in quality-of-life measures ranging from household income to health insurance exist throughout the region.

• Transportation: Funding for transportation has been a significant problem for the Pittsburgh region in the past several years. Despite Gov. Tom Corbett’s recent transportation funding proposal, the fate of public transit in Allegheny County remains unclear. The steep cuts in transit service the Port Authority avoided at the last minute in 2012 remain a possibility until a stable funding solution is found. Data show the cuts could add an extra 11 minutes to the average daily commute. Additionally, a national report on structurally deficient bridges identified 1,133 in the region.

The report and additional information are available at www.pittsburghtoday.org/special_reports.html in the special reports section. Print copies may be requested by contacting Emily Craig at edc20@pitt.edu.

2 Pitt faculty awarded NSF CAREER grants

Two faculty members have won CAREER grants from the National Science Foundation (NSF). The CAREER program supports junior faculty doing groundbreaking research and demonstrating a great understanding of their fields.

Yiran Chen, electrical and computer engineering faculty member in the Swanson School of  Engineering, has been awarded a five-year, $450,000 CAREER grant.

Chen’s research attempts to leverage the unique properties of a memristor device — an emerging nano device that can remember electrical currents in a fashion similar to the way the human brain processes memory — to understand the synaptic behavior in electrical neural networks. The proposed neuromorphic computing circuit would act like a human brain that runs with high-power efficiency and could be manufactured at an ultralow cost.

Emily Elliott, faculty member in environmental isotope geochemistry, has been awarded a five-year, $550,000 CAREER grant.

Elliott, conducting research in the Dietrich School of Arts and Sciences’ Department of Geology and Planetary Sciences, intends to prove that poor constraints on nitrogen releases in urban environments have influenced quite heavily the nutrient sources of urban ecosystems, such as streams and riverine systems. She plans to compare the reactive nitrogen deposition, fluxes and speciation between urban and rural environments; examine the mechanisms that retain nitrogen in urban ecosystems, and determine how the ecosystem responds to the addition of atmospheric nitrate.

Elliott’s research also is aided by the Carnegie Museum of Natural History and Carnegie Science Center.

Covering Medicare D gap would improve mental health outcomes while saving $$$

Medicare Part D generic drug coverage saves money compared to no coverage for those with bipolar disorder and schizophrenia, while also improving health outcomes, according to researchers from the School of Medicine, Graduate School of Public Health and Western Psychiatric Institute and Clinic. They note that policymakers and insurers should consider generic-only coverage, rather than no-gap coverage, both to conserve health-care resources and improve health.

Medicare Part D offers prescription-drug coverage for Medicare beneficiaries. Since the program’s inception in 2006, many enrollees have benefited from improved drug coverage and increased medication use. However, a major concern is the large coverage gap in the standard Part D design, which asks beneficiaries to pay 100 percent of medication costs out-of-pocket. About one-third of all Medicare beneficiaries enter this coverage gap each year and, once there, they often reduce medication use, which may lead to increases in hospitalization and medical spending.

Said Kenneth J. Smith, faculty member in medicine and clinical and translational science and lead author of the study: “This coverage gap is an even larger concern for Medicare beneficiaries with severe mental disorders such as bipolar and schizophrenia.”

Mental health patients are much more likely to enter the gap: 62 percent of Medicare beneficiaries with bipolar disorder and 56 percent of those with schizophrenia entered the gap in 2007. If they discontinue psychotropic medications, they may relapse to more severe episodes and require psychiatric hospitalization. They also experience high rates of comorbid chronic physical conditions such as heart disease and diabetes, which can be exacerbated by untreated mental illness and increase morbidity, medical spending and mortality.

The standard Part D benefit in 2007 included four phases: an initial $265 deductible; a period in which beneficiaries paid 25 percent of drug costs between $265 and $2,400; a coverage gap in which they paid 100 percent of costs between $2,401 and $3,850, at which point they reached their total out-of-pocket spending catastrophic limit, and a catastrophic coverage period during which they paid 5 percent of costs.

Although the standard Part D benefit includes these four phases, some companies offering Part D drug plans modified the design and offered either “actuarially equivalent” or enhanced plans. In 2007, for example, 72 percent of stand-alone Part D plans had the standard coverage gap, 27 percent offered coverage for generic drugs used in the gap and fewer than 1 percent offered coverage for both brand-name and generic drugs.

Of the more than 180,000 patients with bipolar disorder and schizophrenia who were evaluated, 14.6 percent had no gap coverage, and 7.1 percent had generic coverage. The remainder had low-income subsidies with more generous coverage and, therefore, were not strictly comparable to the other two groups. When comparing the no-gap coverage and generic-gap coverage groups, patients with generic coverage had better health outcomes and reduced total medical costs.

The study, published online in February in the American Journal of Managed Care, was done by Smith and Pitt colleagues Seo Hyon Baik, Charles F. Reynolds III, Bruce L. Rollman and Yuting Zhang.

It was supported by the National Institute of Mental Health, the Agency for Healthcare Research and Quality and Pitt’s Central Research Development Fund.

Engineering prof receives NIH grant to study cerebral aneurysms

Anne Robertson has been awarded a $423,852 grant from the National Institutes of Health (NIH) to study the link between hemodynamics and wall structure in cerebral aneurysms. She is a faculty member in the Department of Mechanical Engineering and Materials Science in the Swanson School of Engineering.

Cerebral aneurysms are pathological enlargements of the walls of cerebral arteries and estimated to exist in 5-8 percent of the adult population. Their spontaneous rupture is responsible for 80 percent of subarachnoid hemorrhagic strokes, a devastating disease with high mortality and disability rates.

Robertson’s multidisciplinary team, including Simon Watkins of Pitt’s Center for Biological Imaging and researchers from George Mason University and Allegheny General Hospital, will use an integrated, multiscale approach to determine the link between aneurysm blood flow, wall structure and wall strength. The long-term objectives are to establish new pharmacological treatment methods for cerebral aneurysms and improve clinical treatments that function by altering flow in the aneurysm dome.

Parallel gene evolution may signal parallel functions

Nathan Clark, faculty member in computational and systems biology in the School of Medicine, led a study that found that genes with roles in the same biological pathways change their rate of evolution in parallel, a finding that could be used to discover their functions.

Humans have nearly 21,000 genes that make as many proteins, but the functions of most of those genes have not been determined fully. Knowing what a particular gene does could help unravel the workings of the body, foster understanding of disease processes and identify targets for new drugs.

Said Clark: “We took a close look at the way genes evolved between species and we found an interesting signature. Genes that perform biological functions together have similar evolutionary histories in that the rates at which they change parallel each other. This could allow us to identify partner genes that we might never have suspected to work together in biochemical pathways.”

The researchers studied the evolving genomes of 18 yeast species and 22 mammalian species, looking particularly at genes that are involved in meiosis, a cell division process, and in DNA repair. They found parallel changes, such as acceleration or deceleration, in evolutionary rates among not only genes encoding proteins that physically interact with each other but also among those that had no direct contact but still participated in meiosis or DNA repair pathways.

All genes mutate over time, which can be beneficial, harmful or meaningless. Some yeast species evolved a different method of reproduction and meiosis stopped as it was no longer essential for survival, Clark said. Through subsequent generations, the rate of change in the genes involved in making meiosis proteins accelerated, leading to deterioration of the unnecessary DNA sequences.

“A key question is: How important is that gene at that time?” he said. “If a species encounters a new challenge in its environment, the genes associated with it might have to evolve through subsequent generations in order to adapt that important pathway and ensure species survival.”

By tracking those complementary rate changes, it could be possible to identify which genes participate in the same important pathways, providing clues to their function.

“In the future, a researcher studying a particular disease process might be able to plug in a couple of known genes in a database of evolutionary rate changes to find others that have a parallel history,” Clark said. “That could provide new insight into the workings of the biological pathway of interest.”

Clark collaborated with researchers from Cornell.

Results of the research, supported by NIH, appeared in the February issue of Genetics.

Biomarkers may predict, aid acute kidney injury post-surgery

An international, multicenter study led by John Kellum, critical care faculty member in the School of Medicine, found biomarkers that can tell a physician if a patient is at risk for acute kidney injury. AKI often affects those in intensive care and can occur after serious infections, surgery or taking certain medications. The results provide insight into the potentially deadly condition that affects up to 7 percent of all hospitalized patients.

Existing methods of determining kidney function, such as measuring serum creatinine and urine output, may not indicate changes for several days, allowing time for significant kidney damage to occur. Biomarkers, which are naturally occurring proteins or other molecules in the blood, urine or other body fluids or tissues, may help physicians more accurately determine the risk of AKI in critically ill patients so that early treatment can minimize progression and save lives.

Said Kellum: “If unchecked, AKI can lead to loss of kidney function, often resulting in lower quality of life or even death.”

AKI risk is difficult to determine because the condition typically is caused by something outside of the kidney, including sepsis, nephrotoxins and oxygen deprivation. The study aimed to identify early markers in order to detect AKI when interventions could provide benefit. Researchers collected blood and urine samples from more than 1,000 critically ill patients. The biomarkers, known as TIMP-2 and IGFB7, signal that the kidneys are stressed and not functioning properly but still may recover. They are indicators of cell damage, a key component in the onset of AKI.

The study was published in Critical Care; coauthors were researchers from 35 medical centers worldwide.

The research was sponsored by Astute Medical.

Transplantation for kids with liver tumor on increase

Liver transplantation for hepatoblastoma, the most common liver malignancy in children, is on the rise because more tumors are being detected earlier, thus improving outcomes for patients, according to research led by Rakesh Sindhi, faculty member in the Department of Surgery, Division of Transplantation.

Sindhi and his colleagues observed outcomes in 35 children with hepatoblastoma who received transplants over three decades at Children’s Hospital, where he is co-director of pediatric transplantation at the Hillman Center for Pediatric Transplantation. This is the largest published single-center report in the United States.

Nearly twice as many patients received liver transplants for the malignancy at Children’s Hospital in the most recent decade as compared to the previous two decades. This observation led the group to ask whether the incidence of this malignancy and of liver transplantation for hepatoblastoma has increased in the United States, thereby posing additional challenges in allocating the scarce resource of pediatric livers available, and whether increased use of liver transplantation has improved post-transplantation outcomes for children diagnosed with this form of cancer.

To evaluate national trends, the researchers reviewed data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) registry representing 9.451 percent of the U.S. population from 1975 to 2007; the United Network for Organ Sharing (UNOS) from 1988 to 2010; and Children’s Hospital from 1987 to 2011.

The group found that estimated hepatoblastoma cases in the United States increased four-fold between 1975 and 2007; liver transplantation for hepatoblastoma during the last two decades increased 20-fold between 1988 and 2010, with 153 liver transplants occurring in the last five years. Hepatoblastoma was responsible for 2.8-7.5 percent of all liver transplants annually, surpassing other inoperable liver malignancies as the cause of liver transplantation.

Said Sindhi: “For several years, it has been recognized that many children with hepatoblastoma were born early. Advances in the care of premature babies, and their increased survival as a result, is an important reason for the increased incidence of this tumor.”

Estimates suggest that more than six in 10 children with hepatoblastoma can be cured with surgical removal of the mass after chemotherapy. Liver transplantation is appropriate if the tumor is confined to the liver, but cannot be removed safely because of its location or the involvement of many parts of the liver. Three of four children treated with transplantation can be cured.

Recurrences usually occur within the first two years after transplantation in one-sixth of children undergoing liver transplantation. Recurrences are more common if the liver tumor spread to other organs before transplantation, or if the tumor was less responsive to chemotherapy.

Remarkably, if the tumor outside the liver is removed completely with either chemotherapy or surgery before transplantation, half of such children still can be cured with liver transplantation. In this regard, hepatoblastoma tumors are very different from the liver cancer that can develop in adult and older age groups.

The researchers also found that hepatoblastoma tumors with “anaplastic” or highly aggressive tumor cells were less likely to recur after liver transplantation than what has been reported previously after surgical resection.

Results were published in the February issue of Surgery.

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

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