Tag: artificial intelligence

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For a New Generation of Antibiotics, Scientists are Bringing Extinct Molecules Back to Life – and Discovering the Hidden Genetics of Immunity Along the Way

by Devorah Fischler

Marrying artificial intelligence with advanced experimental methods, the Machine Biology Group has mined the ancient past for future medical breakthroughs, bringing extinct molecules back to life. (Image credit: Ella Marushchenko)

“We need to think big in antibiotics research,” says Cesar de la Fuente. “Over one million people die every year from drug-resistant infections, and this is predicted to reach 10 million by 2050. There hasn’t been a truly new class of antibiotics in decades, and there are so few of us tackling this issue that we need to be thinking about more than just new drugs. We need new frameworks.”

De la Fuente is Presidential Assistant Professor in the Department of Bioengineering and the Department of Chemical and Biomolecular Engineering at the University of Pennsylvania School of Engineering and Applied Science. He holds additional primary appointments in Psychiatry and Microbiology in the Perelman School of Medicine.

De la Fuente’s lab, the Machine Biology Group, creates these new frameworks using potent partnerships in engineering and the health sciences, drawing on the “power of machines to accelerate discoveries in biology and medicine.”

Marrying artificial intelligence with advanced experimental methods, the group has mined the ancient past for future medical breakthroughs. In a recent study published in Cell Host and Microbe, the team has launched the field of “molecular de-extinction.”

Our genomes – our genetic material – and the genomes of our ancient ancestors, express proteins with natural antimicrobial properties. “Molecular de-extinction” hypothesizes that these molecules could be prime candidates for safe new drugs. Naturally produced and selected through evolution, these molecules offer promising advantages over molecular discovery using AI alone.

In this paper, the team explored the proteomic expressions of two extinct organisms –Neanderthals and Denisovans, archaic precursors to the human species – and found dozens of small protein sequences with antibiotic qualities. Their lab then worked to synthesize these molecules, bringing these long-since-vanished chemistries back to life.

“The computer gives us a sequence of amino acids,” says de la Fuente. “These are the building blocks of a peptide, a small protein. Then we can make these molecules using a method called ‘solid-phase chemical synthesis.’ We translate the recipe of amino acids into an actual molecule and then build it.”

The team next applied these molecules to pathogens in a dish and in mice to test the veracity and efficacy of their computational predictions.

“The ones that worked, worked quite well,” continues de la Fuente. “In two cases, the peptides were comparable – if not better – than the standard of care. The ones that didn’t work helped us learn what needed to be improved in our AI tools. We think this research opens the door to new ways of thinking about antibiotics and drug discovery, and this first step will allow scientists to explore it with increasing creativity and precision.”

Read the full story in Penn Engineering Today.

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AI-guided Brain Stimulation Aids Memory in Traumatic Brain Injury

by Erica Moser

Illustration of a human brain
Image: iStock/Ogzu Arslan

Traumatic brain injury (TBI) has disabled 1 to 2% of the population, and one of their most common disabilities is problems with short-term memory. Electrical stimulation has emerged as a viable tool to improve brain function in people with other neurological disorders.

Now, a new study in the journal Brain Stimulation shows that targeted electrical stimulation in patients with traumatic brain injury led to an average 19% boost in recalling words.

Led by University of Pennsylvania psychology professor Michael Jacob Kahana, a team of neuroscientists studied TBI patients with implanted electrodes, analyzed neural data as patients studied words, and used a machine learning algorithm to predict momentary memory lapses. Other lead authors included Wesleyan University psychology professor Youssef Ezzyat and Penn research scientist Paul Wanda.

“The last decade has seen tremendous advances in the use of brain stimulation as a therapy for several neurological and psychiatric disorders including epilepsy, Parkinson’s disease, and depression,” Kahana says. “Memory loss, however, represents a huge burden on society. We lack effective therapies for the 27 million Americans suffering.”

Read the full story in Penn Today.

Michael Kahana is the Edmund J. and Louise W. Kahn Term Professor of Psychology at the University of Pennsylvania. He is a member of the Penn Bioengineering Graduate Group.

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Artificial Intelligence is Leveling Up the Fight Against Infectious Diseases

by Devorah Fischler

Image credit: NIAID

Artificial intelligence is a new addition to the infectious disease researcher’s toolbox. Yet in merely half a decade, AI has accelerated progress on some of the most urgent issues in medical science and public health. Researchers in this field blend knowledge of life sciences with skill in computation, chemistry and design, satisfying decades-long appeals for interdisciplinary tactics to treat these disorders and stop their spread.

Diseases are “infectious” when they are caused by organisms, including parasites, viruses, bacteria and fungi. People and animals can contract infectious diseases from their environments or food, or through interactions with one another. Some, but not all, are contagious.

Infectious diseases are an intractable global challenge, posing problems that continue to grow in severity even as science has offered a steady pace of solutions. The world continues to become more interconnected, bringing people into new kinds and levels of relation, and the climate crisis is throwing environmental and ecological networks out of balance. Diseases that were once treatable by drugs have become resistant, and new drug discovery is more costly than ever. Uneven resource distribution means that certain parts of the world are perennial hotspots for diseases that others never fear.

Cesar de la Fuente brings an expert eye to how AI has transformed infectious disease research in a recently published piece in Science with co-authors Felix Wong and James J. Collins from MIT.

Presidential Assistant Professor in the Department of Bioengineering and the Department of Chemical and Biomolecular Engineering at the University of Pennsylvania School of Engineering and Applied Science, with additional primary appointments in Psychiatry and Microbiology within the Perelman School of Medicine, de la Fuente brings a multifaceted perspective to his survey of the field.

In the paper, de la Fuente and co-authors assess the progress, limitations and promise of research in AI and infectious diseases in three major areas of inquiry: anti-infective drug discovery, infection biology, and diagnostics for infectious diseases.

Read more in Penn Engineering Today.

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Cesar de la Fuente On the “Next Frontier” of Antibiotics

César de la Fuente
César de la Fuente

In a recent CNN feature, César de la Fuente, Presidential Assistant Professor in Bioengineering, Psychiatry, Microbiology, and in Chemical and Biomolecular Engineering commented on a study about a new type of antibiotic that was discovered with artificial intelligence:

“I think AI, as we’ve seen, can be applied successfully in many domains, and I think drug discovery is sort of the next frontier.”

The de la Fuente lab uses machine learning and biology to help prevent, detect, and treat infectious diseases, and is pioneering the research and discovery of new antibiotics.

Read “A new antibiotic, discovered with artificial intelligence, may defeat a dangerous superbug” in CNN Health.

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Penn Bioengineering Graduate Ella Atsavapranee Wins 2023 Fulbright Grant

Ella Atsavapranee (BE 2023)

Twenty-nine University of Pennsylvania students, recent graduates, and alumni have been offered Fulbright U.S. Student Program grants for the 2023-24 academic year, including eight seniors who graduated May 15.

They will conduct research, pursue graduate degrees, or teach English in Belgium, Brazil, Colombia, Denmark, Ecuador, Estonia, France, Germany, Guatemala, India, Israel, Latvia, Mexico, Nepal, New Zealand, the West Bank-Palestine territories, South Korea, Spain, Switzerland, Taiwan, and Thailand.

The Fulbright Program is the United States government’s flagship international educational exchange program, awarding grants to fund as long as 12 months of international experience.

Most of the Penn recipients applied for the Fulbright with support from the Center for Undergraduate Research and Fellowships.

Among the Penn Fulbright grant recipients for 2023-24 is Ella Atsavapranee, from Cabin John, Maryland, who graduated in May with a bachelor’s degree in bioengineering from the School of Engineering and Applied Science and a minor in chemistry from the College. She was offered a Fulbright to conduct research at the École Polytechnique Fédérale de Lausanne in Switzerland.

At Penn, Atsavapranee worked with Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor in Bioengineering, engineering lipid nanoparticles to deliver proteases that inhibit cancer cell proliferation. She has also worked with Shan Wang, Leland T. Edwards Professor in the School of Engineering and Professor of Electrical Engineering at Stanford University, using bioinformatics to discover blood biomarkers for cancer detection. To achieve more equitable health care, she worked with Lisa Shieh, Clinical Professor in Medicine at the Stanford School of Medicine,  to evaluate an AI model that predicts risk of hospital readmission and study how room placement affects patient experience.

Outside of research, Atsavapranee spread awareness of ethical issues in health care and technology as editor-in-chief of the Penn Bioethics Journal and a teaching assistant for Engineering Ethics (EAS 2030). She was also a Research Peer Advisor for the Penn Center for Undergraduate Research & Fellowships (CURF), a student ambassador for the Office of Admissions, and a volunteer for Service Link, Puentes de Salud, and the Hospital of the University of Pennsylvania. She plans to pursue a career as a physician-scientist to develop and translate technologies that are more affordable and accessible to underserved populations.

Read the full list of Penn Fulbright grant recipients for 2023-24 in Penn Today.

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More Cancers May be Treated with Drugs than Previously Believed

by Alex Gardner

3D illustration of cancer cells
nucleus and membrane of pathogen micro organisms in blue background

Up to 50 percent of cancer-signaling proteins once believed to be immune to drug treatments due to a lack of targetable protein regions may actually be treatable, according to a new study from the Perelman School of Medicine at the University of Pennsylvania. The findings, published this month in Nature Communications, suggest there may be new opportunities to treat cancer with new or existing drugs.

Researchers, clinicians, and pharmacologists looking to identify new ways to treat medical conditions—from cancer to autoimmune diseases—often focus on protein pockets, areas within protein structures to which certain proteins or molecules can bind. While some pockets are easily identifiable within a protein structure, others are not. Those hidden pockets, referred to as cryptic pockets, can provide new opportunities for drugs to bind to. The more pockets scientists and clinicians have to target with drugs, the more opportunities they have to control disease.

The research team identified new pockets using a Penn-designed neural network, called PocketMiner, which is artificial intelligence that predicts where cryptic pockets are likely to form from a single protein structure and learns from itself. Using PocketMiner—which was trained on simulations run on the world’s largest super computer—researchers simulated single protein structures and successfully predicted the locations of cryptic pockets in 35 cancer-related protein structures in thousands of areas of the body. These once-hidden targets, now identified, open up new approaches for potentially treating existing cancer.

What’s more, while successfully predicting the cryptic pockets, the method scientists used in this study was much faster than previous simulation or machine-learning methods. The network allows researchers to nearly instantaneously decide if a protein is likely to have cryptic pockets before investing in more expensive simulations or experiments to pursue a predicted pocket further.

“More than half of human proteins are considered undruggable due to an apparent lack of binding proteins in the snapshots we have,” said Gregory R. Bowman, PhD, a professor of Biochemistry and  Biophysics and Bioengineering at Penn and the lead author of the study. “This PocketMiner research and other research like it not only predict druggable pockets in critical protein structures related to cancer but suggest most human proteins likely have druggable pockets, too. It’s a finding that offers hope to those with currently untreatable diseases.”

Read the full story in Penn Medicine News.

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Through the Lens: A Digital Depiction of Dyslexia

by Nathi Magubane

Artist-in-residence and visiting scholar Rebecca Kamen has blended AI and art to produce animated illustrations representing how a dyslexic brain interprets information.

A collage of artwork depicts a series of abstract visualizations of networks.
A work that Penn artist-in-residence Rebecca Kamen produced for the show, “Dyslexic Dictionary” at Arion Press in San Francisco. Here, she reinterprets Ph.D. candidate Dale Zhou’s network visualization. (Image: Cat Fennell)

Communicating thoughts with words is considered a uniquely human evolutionary adaptation known as language processing. Fundamentally, it is an information exchange, a lot like data transfer between devices, but one riddled with discrete layers of complexity, as the ways in which our brains interpret and express ideas differ from person to person.

Learning challenges such as dyslexia are underpinned by these differences in language processing and can be characterized by difficulty learning and decoding information from written text.

Artist-in-residence in Penn’s Department of Physics and Astronomy Rebecca Kamen has explored her personal relationship with dyslexia and information exchange to produce works that reflect elements of both her creative process and understanding of language. Kamen unveiled her latest exhibit at Arion Press Gallery in San Francisco, where nine artists with dyslexia were invited to produce imaginative interpretations of learning and experiencing language.

The artists were presented with several prompts in varying formats, including books, words, poems, quotes, articles, and even a single letter, and tasked with creating a dyslexic dictionary: an exploration of the ways in which their dyslexia empowered them to engage in information exchange in unique ways.

Undiagnosed dyslexia

“[For the exhibit], each artist selected a word representing the way they learn, and mine was ‘lens,’” explains Kamen. “It’s a word that captures how being dyslexic provides me with a unique perspective for viewing and interacting with the world.”

From an early age, Kamen enjoyed learning about the natural sciences and was excited about the process of discovery. She struggled, however, with reading at school, which initially presented an obstacle to achieving her dreams of becoming a teacher. “I had a difficult time getting into college,” says Kamen. “When I graduated high school, the word ‘dyslexia’ didn’t really exist, so I assumed everyone struggled with reading.”

Kamen was diagnosed with dyslexia well into her tenure as a professor. “Most dyslexic people face challenges that may go unnoticed by others,” she says, “but they usually find creative ways to overcome them.”

This perspective on seeing and experiencing the world through the lens of dyslexia not only informed Kamen’s latest work for the exhibition “Dyslexic Dictionary,” but also showcased her background in merging art and science. For decades, Kamen’s work has investigated the intersection of the two, creating distinct ways of exploring new relationships and similarities.

“Artists and scientists are curious creatures always looking for patterns,” explains Kamen. “And that’s because patterns communicate larger insights about the world around us.”

Creativity and curiosity

This idea of curiosity and the patterns its neural representations could generate motivated “Reveal: The Art of Reimagining Scientific Discovery,” Kamen’s previous exhibit, which was inspired by the work of Penn professor Dani Bassett, assistant professor David Lydon-Staley and American University associate professor Perry Zurn on the psychological and historical-philosophical basis of curiosity.

The researchers studied different information-seeking approaches by monitoring how participants explore Wikipedia pages and categorically related these to two ideas rooted in philosophical understandings of learning: a “busybody,” who typically jumps between diverse ideas and collects loosely connected information; and a more purpose-driven “hunter,” who systematically ties in closely related concepts to fill their knowledge gaps.

They used these classifications to inform their computational model, the knowledge network. This uses text and context to determine the degree of relatedness between the Wikipedia pages and their content—represented by dots connected with lines of varying thickness to illustrate the strength of association.

In an adaption of the knowledge network, Kamen was classified as a dancer, an archetype elaborated on in an accompanying review paper by Dale Zhou, a Ph.D. candidate in Bassett’s Complex Systems Lab, who had also collaborated with Kamen on “Reveal.”

“The dancer can be described as an individual that breaks away from the traditional pathways of investigation,” says Zhou. “Someone who takes leaps of creative imagination and in the process, produces new concepts and radically remodels knowledge networks.”

Read the full story in Penn Today.

Rebecca Kamen is a visiting scholar and artist-in-residence in the Department of Physics & Astronomy in Penn’s School of Arts & Sciences.

Dale Zhou is a Ph.D. candidate in Penn’s Neuroscience Graduate Group.

Dani Smith Bassett is J. Peter Skirkanich Professor in Bioengineering with secondary appointments in the Departments of Physics & Astronomy, Electrical & Systems Engineering, Neurology, and Psychiatry.

David Lydon-Staley is an Assistant Professor in the Annenberg School for Communications and Bioengineering and is an alumnus of the Bassett Lab.

 

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ASSET Center Inaugural Seed Grants Will Fund Trustworthy AI Research in Healthcare

by Devorah Fischler

Illustration credit: Melissa Pappas

Penn Engineering’s newly established ASSET Center aims to make AI-enabled systems more “safe, explainable and trustworthy” by studying the fundamentals of the artificial neural networks that organize and interpret data to solve problems.

ASSET’s first funding collaboration is with Penn’s Perelman School of Medicine (PSOM) and the Penn Institute for Biomedical Informatics (IBI). Together, they have launched a series of seed grants that will fund research at the intersection of AI and healthcare.

Teams featuring faculty members from Penn Engineering, Penn Medicine and the Wharton School applied for these grants, to be funded annually at $100,000. A committee consisting of faculty from both Penn Engineering and PSOM evaluated 18 applications and  judged the proposals based on clinical relevance, AI foundations and potential for impact.

Artificial intelligence and machine learning promise to revolutionize nearly every field, sifting through massive amounts of data to find insights that humans would miss, making faster and more accurate decisions and predictions as a result.

Applying those insights to healthcare could yield life-saving benefits. For example, AI-enabled systems could analyze medical imaging for hard-to-spot tumors, collate multiple streams of disparate patient information for faster diagnoses or more accurately predict the course of disease.

Given the stakes, however, understanding exactly how these technologies arrive at their conclusions is critical. Doctors, nurses and other healthcare providers won’t use such technologies if they don’t trust that their internal logic is sound.

“We are developing techniques that will allow AI-based decision systems to provide both quantifiable guarantees and explanations of their predictions,” says Rajeev Alur, Zisman Family Professor in Computer and Information Science and Director of the ASSET Center. “Transparency and accuracy are key.”

“Development of explainable and trustworthy AI is critical for adoption in the practice of medicine,” adds Marylyn Ritchie, Professor of Genetics and Director of the Penn Institute for Biomedical Informatics. “We are thrilled about this partnership between ASSET and IBI to fund these innovative and exciting projects.”

 Seven projects were selected in the inaugural class, including projects from Dani S. Bassett, J. Peter Skirkanich Professor in the Departments of Bioengineering, Electrical and Systems Engineering, Physics & Astronomy, Neurology, and Psychiatry, and several members of the Penn Bioengineering Graduate Group: Despina Kontos, Matthew J. Wilson Professor of Research Radiology II, Department of Radiology, Penn Medicine and Lyle Ungar, Professor, Department of Computer and Information Science, Penn Engineering; Spyridon Bakas, Assistant Professor, Departments of Pathology and Laboratory Medicine and Radiology, Penn Medicine; and Walter R. Witschey, Associate Professor, Department of Radiology, Penn Medicine.

Optimizing clinical monitoring for delivery room resuscitation using novel interpretable AI

Elizabeth Foglia, Associate Professor, Department of Pediatrics, Penn Medicine and the Children’s Hospital of Philadelphia

Dani S. Bassett, J. Peter Skirkanich Professor, Departments of Bioengineering and Electrical and Systems Engineering, Penn Engineering

 This project will apply a novel interpretable machine learning approach, known as the Distributed Information Bottleneck, to solve pressing problems in identifying and displaying critical information during time-sensitive clinical encounters. This project will develop a framework for the optimal integration of information from multiple physiologic measures that are continuously monitored during delivery room resuscitation. The team’s immediate goal is to detect and display key target respiratory parameters during delivery room resuscitation to prevent acute and chronic lung injury for preterm infants. Because this approach is generalizable to any setting in which complex relations between information-rich variables are predictive of health outcomes, the project will lay the groundwork for future applications to other clinical scenarios.

Read the full list of projects and abstracts in Penn Engineering Today.

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Konrad Kording Appointed Co-Director the CIFAR Learning in Machines & Brains Program

Konrad Kording, PhD (Photo by Eric Sucar)

Konrad Kording, Nathan Francis Mossell University Professor in Bioengineering, Neuroscience, and Computer and Information Sciences, was appointed the Co-Director of the CIFAR Program in Learning in Machines & Brains. The appointment will start April 1, 2022.

CIFAR is a global research organization that convenes extraordinary minds to address the most important questions facing science and humanity. CIFAR was founded in 1982 and now includes over 400 interdisciplinary fellows and scholars, representing over 130 institutions and 22 countries. CIFAR supports research at all levels of development in areas ranging from Artificial Intelligence and child and brain development, to astrophysics and quantum computing. The program in Learning in Machines & Brains brings together international scientists to examine “how artificial neural networks could be inspired by the human brain, and developing the powerful technique of deep learning.” Scientists, industry experts, and policymakers in the program are working to understand the computational and mathematical principles behind learning, whether in brains or in machines, in order to understand human intelligence and improve the engineering of machine learning. As Co-Director, Kording will oversee the collective intellectual development of the LMB program which includes over 30 Fellows, Advisors, and Global Scholars. The program is also co-directed by Yoshua Benigo, the Canada CIFAR AI Chair and Professor in Computer Science and Operations Research at Université de Montréal.

Kording, a Penn Integrates Knowledge (PIK) Professor, was previously named an associate fellow of CIFAR in 2017. Kording’s groundbreaking interdisciplinary research uses data science to advance a broad range of topics that include understanding brain function, improving personalized medicine, collaborating with clinicians to diagnose diseases based on mobile phone data and even understanding the careers of professors. Across many areas of biomedical research, his group analyzes large datasets to test new models and thus get closer to an understanding of complex problems in bioengineering, neuroscience and beyond.

Visit Kording’s lab website and CIFAR profile page to learn more about his work in neuroscience, data science, and deep learning.

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Investing in Penn’s Data Science Ecosystem

by Erica K. Brockmeier

As part of a major University-wide investment in science, engineering, and medicine, the Innovation in Data Engineering and Science Initiative aims to help Penn become a leader in developing data-driven approaches that can transform scientific discovery, engineering research, and technological innovation.

From smartphones and fitness trackers to social media posts and COVID-19 cases, the past few years have seen an explosion in the amount and types of data that are generated daily. To help make sense of these large, complex datasets, the field of data science has grown, providing methodologies, tools, and perspectives across a wide range of academic disciplines.

But the challenges that lie ahead for data scientists and engineers, from developing algorithms that don’t exacerbate biases to ensuring privacy protections, are equally complex and, in some instances, require entirely new ways of thinking.

As part of its $750 million investment in science, engineering, and medicine, the University has committed to supporting the future needs of this field. To this end, the Innovation in Data Engineering and Science (IDEAS) initiative will help Penn become a leader in developing data-driven approaches that can transform scientific discovery, engineering research, and technological innovation.

“The IDEAS initiative is game-changing for our University,” says President Amy Gutmann. “This new investment allows us to boost our interdisciplinary efforts across campus, recruit phenomenal additional team members, and generate an even more sound foundation for discovery, experimentation, and design. This initiative is a clear statement that Penn is committed to taking data science head-on.”

Building on a foundation of existing expertise

Led by the School of Engineering and Applied Science, the IDEAS initiative builds upon the steadily gathering momentum of its data-centric research. The Warren Center for Network and Data Sciences has been a major catalyst for this type of work, generating foundational research on ethical algorithms and data privacy, as well as collaborations that have drawn in faculty from the Wharton School, Law School, Perelman School of Medicine, and beyond. In addition, Wharton’s Department of Statistics and Data Science is an active partner in research and teaching initiatives that apply statistical modeling across a wide variety of fields.

“One of the unique things about data science and data engineering is that it’s a very horizontal technology, one that is going to be impacting every department on campus,” says George Pappas, Electrical and Systems Engineering Department chair. “When you have a horizontal technology in a competitive area, we have to figure out specific areas where Penn can become a worldwide leader.”

To do this, IDEAS aims to recruit new faculty across three research areas: artificial intelligence (AI) to transform scientific discovery, trustworthy AI for autonomous systems, and understanding connections between the human brain and AI.

Penn already has a strong foundation in using AI for scientific discovery thanks in part to investments in basic research facilities such as the Singh Center for Nanotechnology and the Laboratory for Research on the Structure of Matter. Additionally, there are centers focused on connecting researchers from different fields to address complex scientific questions, including the Center for Soft and Living Matter, Center for Engineering Mechanobiology, and Penn Institute for Computational Science.

Developing “trustworthy” algorithms, ones that work reliably outside of situations in which they are trained, is another key component of the IDEAS initiative. Ongoing research at the Penn Research in Embedded Computing and Integrated Systems Engineering (PRECISE) Center, the General Robotics, Automation, Sensing & Perception (GRASP) Lab, and DARPA-funded projects on the safety of AI-based aircraft control provide a starting point for furthering Penn’s research portfolio on safe, explainable, and trustworthy autonomous systems.

In the area of neuroscience and how the human brain is similar to AI and machine learning approaches, research from PIK Professor Konrad Kording and Dani Bassett’s Complex Systems lab exemplifies the types of cross-disciplinary efforts that are essential for addressing complex questions. By recruiting additional faculty in this area, IDEAS will help Penn make strides in bio-inspired computing and in future life-changing discoveries that could address cognitive disorders and nervous system diseases.

Read the full story in Penn Today.