Computations and Modeling

Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder brought on by physical and/or psychological trauma. How its symptoms, including anxiety, depression and cognitive disturbances arise remains incompletely understood and unpredictable. Treatments and outcomes could potentially be improved if doctors could better predict who would develop PTSD. Now, researchers using magnetic resonance imaging (MRI) have found potential brain biomarkers of PTSD in people with traumatic brain injury (TBI).

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Researchers at the University of Pittsburgh School of Medicine have combined synthetic biology with a machine-learning algorithm to create human liver organoids with blood- and bile-handling systems. When implanted into mice with failing livers, the lab-grown replacement livers extended life.

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The first full-size 3D bioprinted human heart model using the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) technique has been created by Carnegie Mellon University’s (CMU’s) Adam Feinberg, PhD, and his team. The model, created from MRI data using a specially built 3D printer, realistically mimics the elasticity of cardiac tissue and sutures. This milestone represents the culmination of two years of research, holding both immediate promise for surgeons and clinicians, as well as long-term implications for the future of bioengineered organ research.

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When a person contracts COVID-19, or any other respiratory virus, the immune system springs into action. Body aches and fever are two signs the body is trying to slow the infection and fight off the virus.  The problem is that sometimes, the body doesn’t know when to stop.

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Approximately 85% of late-stage clinical trials of candidate drugs fail because of drug safety problems or ineffectiveness, despite promising preclinical test results. To help improve the design and implementation of clinical trials, the National Institutes of Health has awarded 10 grants to support researchers’ efforts in using tiny, bioengineered models of human tissues and organ systems to study diseases and test drugs. One major goal of the funded projects is to develop ways to better predict which patients are most likely to benefit from an investigational therapy prior to initiating clinical trials.  McGowan Institute for Regenerative Medicine affiliated faculty member Alejandro Soto-Gutierrez, MD, PhD, Associate Professor in the Department of Pathology at the University of Pittsburgh and an affiliated faculty member of the Children’s Hospital of Pittsburgh of UPMC and the Thomas E. Starzl Transplantation Institute, is a co-principal investigator on one of the 10 recently funded projects.

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A bunched-up bundle of a protein-based biologic is practically useless. Unfortunately, protein aggregation creates a common problem in the bioprocessing of many therapeutics. Addressing this issue will probably depend on analyzing the problem in new ways, which could trigger changes in various parts of the process.

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A study from the University of Pittsburgh School of Medicine and Cedars-Sinai addresses a mystery first raised in March: Why do some people with COVID-19 develop severe inflammation? The research shows how the molecular structure and sequence of the SARS-CoV-2 spike protein—part of the virus that causes COVID-19—could be behind the inflammatory syndrome cropping up in infected patients.

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McGowan Institute for Regenerative Medicine affiliated faculty member Michel Modo, PhD, Professor in the Department of Radiology at the University of Pittsburgh with secondary appointments in the Department of Bioengineering and the Center for Neural Basis of Cognition, and colleagues recently published a paper, titled “Mesoscale diffusion magnetic resonance imaging of the ex vivo human hippocampus,” in Human Brain Mapping where the authors anticipate that ex vivo mesoscale imaging will yield novel insights into human hippocampal connectivity. The paper was also the featured cover of the journal.  The abstract of the paper reads:

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Researchers from Sechenov University and University of Pittsburgh discovered that the resistance of innate immune cells, macrophages, to ferroptosis – a type of programmed cell death – depends on the type of their activation. It turned out that cells helping tissues to recover from inflammation were more vulnerable. The researchers identified the mechanisms underlying the cells’ resistance and explained how this research would help regulate inflammation in a paper published in Nature Chemical Biology.  McGowan Institute for Regenerative Medicine affiliated faculty members Valerian Kagan, PhD, DSc, Professor and Vice-Chairman in the Department of Environmental and Occupational Health as well as a Professor in the Department of Pharmacology and Chemical Biology, the Department of Radiation Oncology, and the Department of Chemistry at the University of Pittsburgh, and Ivet Bahar, PhD, Distinguished Professor, the John K. Vries Chair, and the Founding Chair in the Department of Computational & Systems Biology at the University of Pittsburgh’s School of Medicine, are co-authors on the study.

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In the Mechanics of Morphogenesis Lab, team members carry out interdisciplinary research at the interface of physics, engineering, mathematics, and developmental biology.  What you cannot follow in real time in the body, these researchers follow with sophisticated micromechanical test devices and imaging systems.  Once this data is gathered, they then create elaborate computer modeling simulations which can be easily and frequently changed to produce knowledge out of the reach of mathematical analysis or natural experimentation alone.

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McGowan Institute for Regenerative Medicine affiliated faculty member Thomas Rando, MD, PhD, is the co-founder and chair of the board of directors of Fountain Therapeutics.  At Fountain Therapeutics, the research team has combined the expertise of leaders in aging research and computation to build a pipeline of therapeutics aimed at reversing cellular aging. The company’s mission is to decouple aging from disease and significantly extend human health span.

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When a person contracts a respiratory viral infection like COVID-19 or influenza, the immune system responds in a myriad of ways to eliminate the virus. Respiratory viral infections are so dangerous, however, because excessive immune responses may cause extreme lung inflammation. However, new modeling research may help doctors better predict and treat patients who are most at risk to that extreme response.

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Led by Shandong Wu, PhD, associate professor in the Department of Radiology at Pitt, and supported by McGowan Institute for Regenerative Medicine David Vorp, PhD, associate dean for research and John A. Swanson Professor of Bioengineering, the “Pittsburgh Center for Artificial Intelligence Innovation in Medical Imaging” project won a University of Pittsburgh Scaling Grant.  The Scaling Grant provide $400,000 over two years to support detailed project planning, gathering proof-of-concept results, and reduction of technical risk for teams pursuing an identified large extramural funding opportunity. The Scaling Grants are part of the University’s Pitt Momentum Funds, which offer funding across multiple stages of large, ambitious projects.

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The twisting and bending capabilities of the human muscle system enable a varied and dynamic range of motion, from walking and running to reaching and grasping. Replicating something as seemingly simple as waving a hand in a robot, however, requires a complex series of motors, pumps, actuators and algorithms. Researchers at the University of Pittsburgh and Harvard University have recently designed a polymer known as a liquid crystal elastomer (LCE) that can be “programmed” to both twist and bend in the presence of light.

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The paper published by Steven Abramowitch, Associate Professor of Bioengineering at the University of Pittsburgh, and McGowan Institute for Regenerative Medicine affiliated faculty member Pamela Moalli, MD, PhD, Associate Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Urogynecology & Pelvic Reconstructive Surgery, Magee-Womens Hospital of UPMC, University of Pittsburgh, was recently recognized by the editors of the Journal of Biomechanical ok work. The article details complications associated with mechanical loads on synthetic mesh used in pelvic organ prolapse and will be listed as an Editors’ Choice paper in JBME’s Annual Special Issue February 2020.

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Advances in biomimicry – creating biological responses within non-biological substances – will enable synthetic materials to behave in ways that were typically only found in Nature. Light provides an especially effective tool for triggering life-like, dynamic responses within a range of materials. The problem, however, is that the applied light is typically dispersed throughout the sample and thus, it is difficult to localize the bio-inspired behavior to the desired, specific portions of the material.

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The internet of things (IoT) widely spans from the smart speakers and Wi-Fi-connected home appliances to manufacturing machines that use connected sensors to time tasks on an assembly line, warehouses that rely on automation to manage inventory, and surgeons who can perform extremely precise surgeries with robots. But for these applications, timing is everything: a lagging connection could have disastrous consequences.

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Break any bone in the human body and the body can repair the tissue and fix the damage. Yet tooth enamel — the strongest tissue in the human body — cannot repair itself. Still, our teeth last a lifetime.

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Mantle cell lymphoma is an aggressive subtype of non-Hodgkin’s lymphoma that claims the lives of tens of thousands of people every year. Mantle cell lymphoma is considered incurable, even though new treatments have yielded promising results.

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Study: A bioengineering group from the University of Pittsburgh Swanson School of Engineering is bringing the worlds of computational modeling and experimentation closer together by developing a methodology to help analyze the wealth of imaging data provided by advancements in imaging tools and automated microscopes.

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The University of Pittsburgh School of Medicine and Carnegie Mellon University each have been awarded four-year contracts totaling more than $7.2 million from the U.S. Department of Defense to create an autonomous trauma care system that fits in a backpack and can treat and stabilize soldiers injured in remote locations.

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Collaboration and competition are basic instincts among biological species, from the simplest single-celled organisms to reptiles, fish and primates, as well as humans. This dynamic behavior – the result of millions of years of evolution – is difficult to replicate in synthetic systems. However, chemical engineers at the University of Pittsburgh Swanson School of Engineering have recreated these responses in an environment of microscopic particles, sheets, and catalysts, effectively mimicking responses of feeding, fighting, and fleeing.

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McGowan Institute for Regenerative Medicine affiliated faculty member Anna Balazs, PhD, has been at the Swanson School of Engineering since 1987 and is now a Distinguished Professor in chemical and petroleum engineering.  As reported by Amerigo Allegretto for Pittwire, Dr. Balazs is working to transform the future through her research of soft robotics, which could have revolutionary applications across a variety of fields — from surgery in hospitals to rehabilitating patients to providing safer industrial manufacturing conditions.

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The “magic carpet” featured in tales from “One Thousand and One Nights” to Disney’s “Aladdin” captures the imagination not only because it can fly, but because it can also wave, flap, and alter its shape to serve its riders. With that inspiration, and the assistance of catalytic chemical reactions in solutions, a team from the University of Pittsburgh’s Swanson School of Engineering has designed a two-dimensional, shape-changing sheet that moves autonomously in a reactant-filled fluid.

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The University of Pittsburgh research team of

• Piervincenzo Rizzo, PhD, associate professor of civil and environmental engineering,
• Samuel Dickerson, PhD, assistant professor of electrical and computer engineering, and
• McGowan Institute for Regenerative Medicine affiliated faculty member Ian Conner, MD, PhD, assistant professor of ophthalmology and bioengineering,

recently received funding via a $360,000 grant from the National Science Foundation.  Dr. Rizzo and his team are currently measuring the internal pressure of objects, such as a piece of steel girder and a tennis ball, with the end goal of calculating corrosive deterioration in pipelines in the natural gas, hazardous liquid and liquefied natural gas plant industries.  Other applications being researched for this technology include, most notably, for measuring and monitoring eye pressure in glaucoma patients.

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McGowan Institute for Regenerative Medicine affiliated faculty member Shilpa Sant, PhD, Assistant Professor of Pharmaceutical Sciences, has received a 7-year R37 MERIT Award from the National Cancer Institute (NCI), NIH, for her project entitled, “Three-dimensional organoid models to study breast cancer progression.” This grant is funded by the NCI under the Cancer Tissue Engineering Collaborative (TEC) Research Program that aims to support the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. The total funding for the first 5 years is $2.7 million.

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Buprenorphine (BUP) is approved for the treatment of opioid addiction. The current dosing regimen of BUP in pregnant women is based on recommendations designed for non-pregnant adults, but physiological changes during pregnancy may alter BUP exposure and efficacy.

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Embedding a decision support tool in the hospital electronic health record increases detection of acute kidney injury, reducing its severity, and improving survival, according to new research from the University of Pittsburgh and UPMC.

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The National Institutes of Health (NIH) has awarded a $1.2 million grant to a multi-institutional project led by the University of Pittsburgh to engineer a 3-dimensional joint-on-a-chip called the “microJoint,” to replicate a human joint on a small scale. The microJoint will be used to study and test drugs for the treatment of arthritic joint diseases. McGowan Institute for Regenerative Medicine associate director Rocky Tuan, PhD, is the principal investigator of the award.

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Molecular chelating agents are used in many areas ranging from laundry detergents to paper pulp processing to precious metal refining. However, some chelating agents, especially the most effective ones, do not degrade in nature and may pollute the environment. With support from the National Science Foundation (NSF), researchers at the University of Pittsburgh Swanson School of Engineering are developing machine learning procedures to discover new chelating agents that are both effective and degradable.

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“When there are one or two bacteria, they behave in a certain way,” said McGowan Institute for Regenerative Medicine affiliated faculty member Anna Balazs, PhD, Distinguished Professor of Chemical Engineering and the John A. Swanson Chair of Engineering at the University of Pittsburgh’s Swanson School of Engineering. “But suddenly, when there is a critical threshold of bacteria, the bacteria can sense this increase in population and they dramatically change their behavior.”

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McGowan Institute for Regenerative Medicine affiliated faculty members at the University of Pittsburgh have been awarded grants from the National Science Foundation (NSF) and the National Institutes of Health (NIH) to study diverse aspects of how the brain works.

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From the smallest cell to humans, most organisms can sense their local population density and change behavior in crowded environments. For bacteria and social insects, this behavior is referred to as “quorum sensing.” Researchers at the University of Pittsburgh’s Swanson School of Engineering have utilized computational modeling to mimic such quorum sensing behavior in synthetic materials, which could lead to devices with the ability for self-recognition and self-regulation.

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The National Science Foundation recently awarded a 3-year, $300K grant entitled, “SusChEM: machine learning blueprints for greener chelants.”  McGowan Institute for Regenerative Medicine affiliated faculty member Eric Beckman, PhD, Bevier Professor of Engineering in the Chemical Engineering Department at the University of Pittsburgh and a Co-Director of the Mascaro Center for Sustainable Innovation, is the project co-principal investigator along with principal investigator John Keith, PhD, R.K. Mellon Faculty Fellow in Energy, Department of Chemical Engineering.  The award begins August 1, 2017, and extends through July 31, 2020.

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McGowan Institute for Regenerative Medicine Director William Wagner, PhD, Professor of Surgery, Bioengineering and Chemical Engineering at the University of Pittsburgh, Chairman of the Tissue Engineering and Regenerative Medicine International Society (TERMIS) – Americas, Deputy Director of the NSF Engineering Research Center on Revolutionizing Metallic Biomaterials, and Chief Scientific Officer of the Armed Forces Institute of Regenerative Medicine, was a member of the keynote panel of the recently held RAPID + TCT, North America’s preeminent event for discovery, innovation, and networking in 3D manufacturing.

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The U.S. Department of Defense recently announced the awarding of their 2017 large, multi-university grants in their MURI program.  One of the 23 awards will go to a team of researchers led by McGowan Institute for Regenerative Medicine affiliated faculty member Anna Balazs, PhD, Distinguished Professor of Chemical Engineering and the Robert v. d. Luft Professor, Department of Chemical & Petroleum Engineering, University of Pittsburgh.  Dr. Balazs will serve as the PI on the project entitled “Adaptive Self‐Assembled Systems:  Exploiting Multifunctionality for Bottom‐up Large Scale Engineering” with the team spanning the University of Pittsburgh, Harvard, Northwestern, and the University of Illinois.  The award is for 5 years at $1.5 million per year.

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Capitalizing on previous studies in self-powered chemo-mechanical movement, researchers at the University of Pittsburgh’s Swanson School of Engineering and Penn State University’s Department of Chemistry have developed a novel method of transporting particles that utilizes chemical reactions to drive fluid flow within microfluidic devices. Their research, “Harnessing catalytic pumps for directional delivery of microparticles in microchambers,” was published recently in the journal, Nature Communications.

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The work of McGowan Institute for Regenerative Medicine affiliated faculty members Ruben Zamora, PhD, Research Associate Professor at the University of Pittsburgh in the Department of Surgery, and Yoram Vodovotz, PhD, Professor in the Department of Surgery with secondary appointments in the Department of Computational & Systems Biology, the Department of Bioengineering, the Department of Immunology, the Department of Communication Science and Disorders (of the School of Health and Rehabilitation Science), and the Clinical and Translational Science Institute, and also the Director of the Center for Inflammation and Regenerative Modeling at the McGowan Institute, is featured in the November 2016 issue of the publication, Molecular Medicine.

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For as long as scientists have been listening in on the activity of the brain, they have been trying to understand the source of its noisy, apparently random, activity. In the past 20 years, “balanced network theory” has emerged to explain this apparent randomness through a balance of excitation and inhibition in recurrently coupled networks of neurons. A team of scientists has extended the balanced model to provide deep and testable predictions linking brain circuits to brain activity.

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Visual hallucinations … everyone has heard of them, and many people have experienced the sensation of “seeing” something that isn’t there. But studying the phenomenon of hallucinations is difficult: they are irregular, transitory, and highly personal—only the person experiencing the hallucination knows what he or she is seeing, and representations of what’s being seen are limited to verbal descriptions or drawings.

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