University Times

Enzymes may create self-powered fluidic devices

Researchers at the Swanson School of Engineering, with collaborators at Penn State University’s chemistry department, have discovered a novel way of using the chemical reactions of certain enzymes to trigger self-powered mechanical movement.

The computational modeling developed by Anna C. Balazs, distinguished professor of chemical and petroleum engineering, with postdoctoral associate Henry Shum and their Penn State colleagues, revealed that simple enzymatic reactions can drive complex, time-dependent flows. Their research, “ Convective flow reversal in self-powered enzyme micropumps,” was published in Proceedings of the National Academy of Sciences.

Said Balazs: “Small-scale chemical synthesis and analysis commonly occur in fluid-filled chambers and require monitoring and intervention. Ideally, you would prefer that the process be as autonomous as possible.” The pumps used by the researchers provide precise control over flow rate without the aid of an external power source and are capable of turning on in response to specific chemicals in solution. The surface-bound enzymes can be used to combine sensing and fluidic pumping into a single self-powered microdevice.

The team examined the factors that cause variations in density in the enzymatic reactions and developed a mathematical model. The model pinpointed where the relative density and relative diffusivity of the reagents and products control the behavior, enabling the researchers to map a parameter range where the fluid could move in different directions at different times. Such a reaction causes a change in the density of the fluid, leading to a fluid flow. This creates a chemo-mechanical transduction — chemical energy creating mechanical action — in the way that the human body converts chemical energy from food into movement.

These experiments with urease enzyme at Penn State agreed with the Pitt simulations. Unlike other enzymes, which always pumped fluid in the same direction, urease generated an unexpected flow pattern, with the direction of flow changing over space and time.

Even more complex behavior could be built up using different enzymes placed at different locations to create a dynamic cascade of events. The resulting chemical reaction network is analogous to an electrical system in a computer. Since each enzyme will behave differently, a multistage chemical reaction could be “programmed” into an experiment, with each step generating flow as determined by the action of a specific enzyme.

“Much like Disney’s ‘The Sorcerer’s Apprentice,’ where you could snap your fingers and have mops and brooms clean your room for you, it’s a scientist’s wish to create systems which behave autonomously and controllably,” Balazs said. Such self-powered enzyme pumps could be used as self-regulated, stimuli-responsive, active delivery vehicles.

Testosterone benefits men over 65

The Graduate School of Public Health was among a dozen sites nationwide to participate in the first clinical trial showing that testosterone treatment for men aged 65 and older improves sexual function, walking ability and mood. Results of the Testosterone Trials (TTrials), led by the Perelman School of Medicine at the University of Pennsylvania and funded by the National Institutes of Health (NIH), were published in the New England Journal of Medicine.

Said Jane A. Cauley, faculty member in the Department of Epidemiology, co-author and chair of the TTrials recruitment committee and principal investigator at the study’s Pittsburgh site: “Previous testosterone trials in older men yielded equivocal and inconsistent results. We showed that testosterone improved men’s impression that their sexual function and walking ability had improved, suggesting that these effects are clinically important.”

The TTrials are a coordinated group of seven trials testing the effect of a testosterone gel compared with a placebo gel, and researchers have analyzed the results of the three primary trials — sexual function, physical function and vitality. They found that testosterone treatment increased the blood testosterone level in men 65 and older to levels comparable to mid-normal for young men. Testosterone also improved all aspects of sexual function, including sexual activity, sexual desire and the ability to get an erection. Testosterone treatment did not significantly improve distance walked in six minutes when only men enrolled in the physical function trial were considered, but did increase the distance walked when all men in the TTrials were considered. The treatment did not improve energy, but did improve mood and depressive symptoms.

The authors caution that decisions about testosterone treatment also will depend on the results of the other four trials — cognitive function, bone, cardiovascular and anemia — and the risks of testosterone treatment.

In 2003, the Institute of Medicine reported that there was insufficient evidence to support any beneficial effect of testosterone in such men. This report was the impetus for TTrials, which now are the largest trials to examine the efficacy of testosterone treatment in men 65 and older whose testosterone levels are low due seemingly to age alone. TTrials researchers screened 51,085 men to find 790 who qualified with a sufficiently low testosterone level and who met other criteria; 78 of the men were enrolled from the Pittsburgh area.

The men enrolled were randomized into two groups: one to apply the daily testosterone gel and the other a daily placebo gel, for one year. Efficacy then was evaluated at months three, six, nine and 12. Sexual function was assessed by questionnaires; physical function was measured by questionnaires and the distance walked in six minutes; vitality, mood and depressive symptoms also were evaluated using questionnaires.

Across the three trials, adverse events — including heart attack, stroke, other cardiovascular events and prostate conditions — were similar in men who received testosterone and those who received placebo. However, the number of men in the TTrials was too small to draw conclusions about the risk of testosterone treatment, which the researchers say would require a larger and longer trial.

The TTrials were conducted at 11 additional medical centers across the country: Albert Einstein College of Medicine; Baylor College of Medicine; Brigham and Women’s Hospital; Harbor-UCL Medical Center; University of Alabama-Birmingham; Northwestern University Feinberg School of Medicine; Puget Sound Health Care System; University of California-San Diego School of Medicine; University of Florida School of Medicine; University of Minnesota School of Medicine; and Yale School of Medicine.

The TTrials were supported by the NIH’s National Institute on Aging, National Heart, Lung and Blood Institute, the National Institute of Neurological Diseases and Stroke, the National Institute of Child Health and Human Development and AbbVie (formerly Solvay and Abbot Laboratories).

Modeling the impact of solar power

Nationwide, solar panels are contributing more and more power to the electrical grid. This can present a problem, putting the grid at risk when too much power enters the system, potentially overloading it or causing abnormal voltages. Electric utilities need better tools to monitor the impact of solar power, which is governed by many variables including cloud cover, wind speed, temperature and a large number of small producers contributing to the system.

Tom McDermott, electrical and computer engineering faculty member in the Swanson school, is part of a multipronged, federally funded $4 million effort to more quickly and accurately model the impact of solar power on the grid.

Said McDermott about Pitt’s contribution to the project: “We’re working on what’s really a big-data application. We want to simulate a whole year [on the grid] using random variables. We want to make the simulations run faster and remain accurate.”

Speed and accuracy are vital benchmarks. When a solar generator applies to connect to the grid, the utility typically has to respond within 30 days, and it’s important to understand the potential impact of a new contributor to the system.

If peak voltage simulations are off by even 1 percent, McDermott said, there can be very negative impacts on the system, degrading the utilities’ reliability and causing significant damage to equipment.

“We hope that by the end of the grant we will have created a tool that can be deployed in the commercial software space,” McDermott said. “It will allow utilities to simulate, plan and design for these changes in the grid.”

Other partners in the grant are Sandia National Laboratories, National Renewable Energy Laboratory, Georgia Institute of Technology, the Electric Power Research Institute and CYME.

Community  pharmacy data  project funded

Janice L. Pringle, pharmacy and therapeutics faculty member in the School of Pharmacy, has received support from UPMC Health Plan for the study “Implementing Screenings, Brief Intervention (SBI) Within Community Pharmacies.”

Pringle’s program and evaluation research unit (PERU) will train two Giant Eagle pharmacy clinical coordinators to employ SBI using motivational interviewing principles and implementation science principles and to evaluate data from the project.  They then will train approximately 25 community pharmacists in these interventions and techniques, with PERU’s assistance.

PERU will provide an organizational health assessment, including strengths and weaknesses, and determine what actions need to be taken to achieve UPMC Health Plan’s long-range vision.

This project will provide additional analysis of data from a previous study, which evaluated the effectiveness of a patient care approach involving screening and brief interventions upon medication adherence and downstream health care costs. Additional analysis will provide information concerning which patients responded best to the SBI intervention and what health care costs and events were most impacted by the patient health changes associated with SBI.

—Compiled by Marty Levine

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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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