University Of Delaware

NIH Research Projects · FY 2025 · 2025-06

PROJECT SUMMARY The biggest translational hurdle to advancing inhaled therapeutic and vaccine systems is predicting how they will work in the lung. Predictions are challenged by the complex variability of airway structure and motion, the tremendous surface area, and the highly coupled physical phenomena of orally inhaled and nasal drug products (OINDPs). Given the high degree of complexity, there remain no preclinical tools capable of measuring spatial deposition of an entire OINDP dose under simulated breathing conditions. Without knowing where aerosols deposit in each individual, predictions of how well the therapeutic will work once there are severely insufficient. This dearth of realistic in vitro models leads to a complete lack of high throughput screening approaches to new inhalation therapies and creates significant challenges to establishing efficacy, toxicity, and/or bioequivalence (BE) of OINDPs. Given this major bottleneck, pulmonary drug delivery remains a low pipeline priority, despite the overwhelming potential to directly treat a plethora of respiratory diseases. To address this, our lab has created a multiscale dynamic preclinical tool to spatial measure deposition as a function of patient-specific breathing, anatomy, and disease state. Coined the “total inhalable deposition in an actuated lung” (TIDAL) model, this platform leverages advances in additive manufacturing to recreate spatial aerosol collection efficiencies across the five lung lobes. Our overall goal in this project is to realize the potential of the TIDAL tool as an effective measure of inhaled deposition to address outstanding issues in inhalation therapeutics. In Aim 1, we will validate healthy an adult TIDAL prototype with clinical dosimetry benchmarks for aerosols of different average aerodynamic diameters and breathing profiles and identify an optimal upper airway. In Aim 2, we will develop advanced features of the TIDAL model to capture interpatient variability, including aspects of airway disease and altered ventilation. In Aim 3, we will upgrade the TIDAL model to include representative humidity and mucosal mimicry to effectively evaluate DPI products. Progressing in parallel, these aims will yield 1) a novel, integrated preclinical tool to measure spatial deposition and improve predictions of inhalation efficacy (and/or toxicity), 2) broad correlations between regional deposition, BE, and existing in vitro measures, and 3) a platform technology that can support therapeutic development for a wide range of respiratory patients and disease pathologies. The integrated multiscale features of TIDAL within a single physical mode of the entire lung volume will enable the first experimental quantification of how patient geometry, disease, breath maneuver, and aerosol size combine to dictate lung response, leading to a transformative step-change in inhalation therapeutic approaches. The project will catalyze new OINDP model creations and transform opportunities in inhalation medicine.

NIH Research Projects · FY 2025 · 2025-06

Abstract: Advances in natural language processing can build on prior breakthroughs in image processing to offer clinicians new AI tools in the fight against prostate cancer, the second leading cause of cancer death. Current AI for interpreting multi­parametric MRI (mp­MRI) scans, the primary imaging modality in PCa, achieves high performance through training on visual encodings of human expertise (e.g. lesion annotations). Such models fail at translation to patient care because they do not derive and communicate their results through the standardized format accepted by clinicians, PI­RADS. The expertise encoded in PI­RADS reports offers a major resource for training AI to achieve clinical acceptance. The proposed research is needed to overcome two major gaps in knowledge necessary to develop advanced AI systems that can learn from both visual (annotations) and text (PI­RADS) exemplars. (1) Data availability: Public PCa data repositories provide mp­MRI scans and annotations but omit accompanying PI­RADS reports. (2) AI modeling: Existing AI approaches focus on image processing and lack the capacity to integrate complex radiologist expertise expressed through language. This study will test the hypothesis that PI­RADS reports can be made machine­readable and combined with visual data so that AI can be trained to interpret MRIs according to the reasoning processes of radiologists. Memorial Sloan Kettering (MSK) radiologists and University of Delaware (UD) researchers will collaborate to achieve the following aims. Aim 1): The MSK team will curate a comprehensive dataset by annotating 300 public and 50 MSK MRI scans with corresponding PI­RADS reports. The UD team will leverage GPT­4 to automatically extract radiologists’ reasoning processes, i.e., radiologist rationale, from each report. Aim 2): The UD team will develop a Prostate Vision­ Language Model (ProstateVLM), building on supportive pilot data to leverage medical foundation models and successfully integrate both images (MRIs and annotations) and text (rationales) in a uniform embedding space. ProstateVLM will be trained on the comprehensive dataset to accurately segment the prostate gland, anatomical zones, and lesions on MRI scans and align its segmentation with radiologist expertise. Aim 3): The UD team will evaluate whether inclusion of radiologist rationales from PI­RADS as training data improves MRI segmentation vs. training on images alone, measured by Dice Score, mAP, etc. The MSK team will evaluate whether ProstateVLM’s interpretations of MRIs align with those of radiologists, measured by a questionnaire scoring metrics for accuracy and completeness. To support future research, the curated dataset and ProstateVLM will be shared through the Cancer Imaging Archive (TCIA).

NSF Awards · FY 2025 · 2025-05

Tao Li of University of Delaware is supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry to develop new computational methods for modeling molecular polaritons—hybrid states arising from the interaction between molecules and confined light inside optical cavities. These hybrid states have shown promise for controlling chemical reactions and energy transfer in unconventional ways. However, current theoretical models fail to capture the complexity of real-world experiments, which involve millions of molecules interacting with a complicated photonic environment. To bridge this gap, this project will develop innovative simulation tools by integrating molecular dynamics, first-principles electronic structure methods, and computational electrodynamics. These tools will enable more accurate modeling of polariton chemistry in realistic experimental conditions, ultimately deepening our understanding of how strong light-matter interactions influence molecular processes. In addition to scientific advancements, the team will make their computational tools openly available to the general public. Dr. Li’s research will focus on developing three theoretical frameworks for modeling collective strong coupling in molecular ensembles. First, the team will implement the mesoscale molecular dynamics simulation approach to describe vibrational strong coupling in Fabry–Pérot cavities by explicitly accounting for multimode photonic environments. Second, this project will develop a first-principles simulation approach to study electronic excited-state dynamics under both vibrational and electronic strong couplings, thus enabling a unified description of nonadiabatic processes under strong coupling. In addition, a semiclassical computational electrodynamics approach will be developed which treats the bulk molecular ensemble as a dielectric medium while explicitly simulating the quantum dynamics of impurity molecules. By combining these approaches, the aim is to advance the theoretical modeling of polariton chemistry and provide powerful computational tools for understanding strong light-matter interactions at experimentally relevant scales. Beyond the polariton study, the developed computational tools can also advance research in fields such as plasmonic catalysis and plasmon-enhanced spectroscopy. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-04

NON-TECHNICAL DESCRIPTION: Thin films of metal oxides such as ferrous oxide and titania have long been studied for their various unique physical properties, such as magnetism and superconductivity. It is only in the past few years, however, that research in oxides comprised of metallic elements lower in the periodic table has gained prominence. Oxides composed of these metals exhibit unusual properties when they conduct electricity making them strong candidates for use in quantum computation technologies. This project focuses on the synthesis of oxide thin films comprised of elements in the fourth and fifth rows of the periodic table. Researchers are studying the unusual behavior derived from materials comprised of two different elements made with atomically sharp interfaces using a technique called molecular beam epitaxy. By alternating layers of each material in a sandwich structure to produce repeating interfaces, the research focuses on making a material that exhibits the properties of the interface many times over. Through two outreach programs, exposure to science in rural and underserved areas of Alabama is broadened to groups that are not introduced to science in their daily lives. The investigator teaches annual seminars in Alabama prisons through the Alabama Prison Arts and Education Project about the applications of physics and materials science to new technologies, offering non-traditional students scientific enrichment and education during their rehabilitation that is not otherwise available. The researchers also lead the annual Gameday Physics outreach event to perform science demonstrations and introduce physics research to a broad and diverse audience at highly-attended football games on the Auburn University campus. TECHNICAL DETAILS: Complex oxides comprised of 4d and 5d transition metals exhibit significantly higher spin-orbit coupling than those comprised of 3d elements. These materials have been predicted to exhibit high temperature superconductivity and other emergent topological phenomena when formed in epitaxial thin film heterostructures and superlattices. These properties make 4d and 5d materials promising for use as materials to enable topological quantum computation. In this project, systematic studies of synthesis of several candidate 4d and 5d complex oxides via hybrid molecular beam epitaxy are performed. Using this novel approach, a metal-organic precursor replaces the traditional elemental source for the transition metal, enabling easier synthesis and producing higher quality materials. Exploration of emergent interfacial phenomena includes high-temperature superconductivity, ferroelectricity, and topological electronic states. By synthesizing superlattice films comprised of repeating interfaces, the research focuses on the development of materials that exhibit interfacial phenomena in a bulk film. This project provides educational experiences for undergraduate students to learn about materials characterization through machine learning analysis of diffraction and spectroscopy data. Computational codes to analyze such data are shared for the research community to advance real-time analysis of film synthesis. Graduate student researchers gain experience in materials synthesis and characterization in the lab and at user facilities around the world. Such experiences help prepare students for careers in materials research in the integrated circuit and electronic device industry. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-04

The project will employ a turbulence-resolving simulation framework with realistic bathymetry and density stratification to investigate the impact of Langmuir turbulence on the regional estuarine circulation. The investigators will develop a three-dimensional time-dependent, nonhydrostatic simulation framework with realistic bathymetry. They will analyze high-resolution satellite imagery and observations from a recent field campaign to identify wind conditions favorable for Langmuir turbulence generation in estuaries. The project will fundamentally advance understanding of the physics of estuarine transport processes and the dynamics of Langmuir turbulence. The research will address the following hypotheses: Langmuir turbulence is a predominant process for wind directions with long fetches and relatively weak tidal currents; For favorable conditions, Langmuir turbulence greatly enhances vertical mixing processes thereby substantially altering the estuarine circulation; and surface convergence regions in the presence of Langmuir turbulence compete with those due to the lateral estuarine flow thereby controlling the aggregation and trapping of buoyant material. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-04

Ankle braces are prescribed to make walking easier for people with disrupted ankle function. These braces can help some people, but many brace users still have difficulty walking. One reason braces may not provide benefit is that the ankle is complex, but most braces act like a simple spring. Another reason is that current methods for brace customization are based on trial and error as there is not a good model for how to change the brace’s properties to best meet each person’s needs. Ankle braces with tailored properties that better mimic normal ankle function may make it easier to walk for people with ankle injuries. The purpose of this study is to develop an ankle brace model with more complex properties based on typical ankle function. The project will evaluate how changing different model properties in the brace impacts how healthy and post-stroke people walk. Results from this study are expected to advance our understanding of how to design and prescribe personalized ankle braces and other assistive devices. This collaborative project between the University of Colorado at Boulder and the University of Delaware will investigate the potential benefits of passive ankle-foot orthoses (AFOs) with customized and biomimetic stiffness profiles. The project's goals will be achieved by first using AFO benchtop testing data to develop a control scheme for an AFO emulator that can effectively mimic both dual-stiffness and single-stiffness passive AFOs in both plantarflexion and dorsiflexion. Then, human-in-the-loop optimization (HILO) will be performed over a range of input control parameters for both dual-stiffness and single-stiffness profiles to determine how these optimized profiles affect walking function in (a) healthy individuals as a proof of concept and (b) individuals post-stroke. Walking speed will be used as the primary optimized outcome metric, with metabolic cost as a secondary metric. User-preferred parameters will also be determined and compared with the optimal parameters determined from HILO for each population. The fundamental knowledge gained from this study will provide critical understanding necessary to positively transform the way passive AFOs and other novel assistive devices are designed and customized. Such advancements will improve the quality of life of persons with disabilities by enhancing mobility. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

This project provides funding for the Research Vessel Hugh R. Sharp to conduct oceanographic research missions supported by the National Science Foundation. The oceanographic research vessels of the Academic Research Fleet (ARF), operated by the academic institutions within the University-National Oceanographic Laboratory System (UNOLS) framework are multi-use facilities used to expand knowledge of the ocean environment. The surface work of these ships is complemented by human-occupied, remotely operated, and autonomous undersea vehicles and sensors that provide vital tools to understand the oceans and their resources. These seagoing research and educational facilities enable scientists and students to study natural phenomena and train future scientists while on board state-of-the-art oceanographic research vessels utilizing high-quality instrumentation. The ship operators will also conduct learning activities for students and the general public including hands-on demonstrations of marine science research guided by faculty, students, and ship crew members. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

With the support of the Chemical Catalysis program in the Division of Chemistry, Carsten Milsmann of West Virginia University will study transition metal catalysts based earth-abundant metals, specifically iron and cobalt. The construction of complex organic molecules is an important target in the development of novel pharmaceuticals, functional materials, and consumer products. The elaboration of building blocks such as olefins, aromatics, and saturated hydrocarbons into more complex structures can be achieved by chemical reactions involving carbene fragments, which typically require metal catalysts to proceed efficiently. The best catalyst systems available currently rely heavily on rare and precious metals, which increases the cost of the resulting products and presents sustainability challenges due to limited resource availability. This research aims to develop design principles for earth-abundant metal complexes that can replace precious metals in carbene transfer catalysis. The development of iron- and cobalt-catalyzed processes in particular has the potential to improve fine chemical production in the United States. Dr. Milsmann and his students will actively participate in community outreach involving the development and presentation of chemistry demonstrations at the K-12 level, and will develop new hands-on experiments for middle and high school students. With the support of the Chemical Catalysis program in the Division of Chemistry,Carsten Milsmann of West Virginia University will study the electronic structures of four-coordinate iron- and cobalt-carbene complexes and their resulting reactivities as competent intermediates in carbene transfer catalysis. Of particular interest are complexes with square-planar or cis-divacant octahedral geometries that possess open coordination sites adjacent to the carbenoid ligand. The first aim of these studies is to establish how changes in the molecular structure and coordination geometry influence the electronic structures of the resulting complexes and their reactive metal carbenoid fragments. The second aim seeks to connect differences in electronic structure to changes in reactivity by studying catalytically competent, isolable iron- and cobalt-carbene complexes. A key hypothesis of the proposed research is that open coordination sites in square-planar carbene complexes will allow unprecedented control over the regioselectivity of carbene transfer using directing groups on the substrates. Finally, the third aim is to investigate the potential of four-coordinate iron carbenes to engage in [2+2] cycloaddition chemistry, which is a key step toward iron catalyst-mediated olefin metathesis. The proposed complexes possess coordinatively unsaturated metal centers, potentially opening up new opportunities for the control of reactivity compared to previously reported iron-carbene complexes. These studies will directly probe recent computational predictions that have identified iron-carbene complexes with pincer-type ligands as promising candidates for olefin metathesis catalysis. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

Microbes inhabit nearly every environment on Earth, acting as key components of ecosystems, drivers of biogeochemical cycles and significantly impacting human health. The ability to thrive in diverse environments is in part due to microbes’ ability to convert diverse energy sources into cellular energy, often via multiple branched electron transport chains. Cytochromes c (cyt c) are a key component of most electron transport chains and much effort has been devoted to understanding the diverse roles of individual cyt c isoforms. Over one hundred different cyt c have been identified, yet all are made in the same way, a process called cyt c biogenesis. Despite the large number and diversity in function of cyt c, only three pathways exist to make it: System I (prokaryotes), System II (prokaryotes), and System III (eukaryotes). Understanding how these three pathways function is a fundamental biological question that is still not well understood. This project will obtain a detailed, mechanistic understanding of the bacterial System II cyt c biogenesis pathway through structure-function analysis. The team integrates undergraduate researchers into the project via direct participation in the research objectives. Additional educational opportunities from this project include classroom experiences to expand undergraduate knowledge, both of research and of STEM careers. These activities will increase STEM identity as a way to improve retention in STEM, leading to a more multitalented STEM workforce. Cyt c biogenesis requires the covalent attachment of heme to a conserved motif on cyt c. This project focuses on the bacterial System II cyt c biogenesis pathway composed of two proteins, CcsB/A, proposed to be a bi-functional enzyme for transmembrane heme transport and attachment to cyt c. Comparison of System II proteins across bacteria has determined that CcsB/A’s have low sequence identity, can be encoded with different genetic arrangements and exhibit variability in protein size and predicted structure. Therefore, a comparative study of System II pathways will be undertaken to 1) determine if holocytochrome c synthase function is conserved despite protein variability and 2) elucidate the System II/cytochrome c interaction domain to determine specificity of heme attachment. Additionally, the distribution of bacterial cyt c pathways, System I and II, across bacteria will be determined bioinformatically to define the evolution of these pathways. These in-depth structure-function studies will provide a mechanistic understanding of System II, provide tools that can be expanded for the study of the other cytochrome c biogenesis pathways and lay the foundation for future studies to probe the regulation and impact of cyt c biogenesis in the context of bacterial metabolism and bioenergetics. This project is jointly funded by the Cellular Dynamics and Function program, the Division of Molecular and Cellular Bioscience, and the Established Program to Stimulate Competitive Research (EPSCoR). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

This collaborative project is led by the University Delaware. The project's vision is to create an inclusive, open, collaborative research ecosystem where faculty and students are supported and encouraged to expand their interests. A highly skilled workforce will be expanded and retained, and research innovation and interconnectedness will be increased across all state priority sectors. The project has potential to foster new collaborations across institutions in Delaware. Additionally, through its focus on strengthening the state's research infrastructure, the project has potential to strengthen the state's data and intellectual property infrastructure, improve communication and access to STEM programming, and support entrepreneurial training. By addressing these needs, this project has potential to boost cutting-edge research carried out by interdisciplinary teams, resulting in substantial gains in Delaware's knowledge-based economy. This collaborative project is led by the University Delaware in partnership with the Delaware EPSCoR State Committee, Delaware State University, Delaware Technical Community College, Goldey-Beacom College and Wilmington University. The project goals are to form lasting networks that facilitate access to expertise, specialized equipment and resources, and support for meaningful experiential-entrepreneurial learning opportunities. To achieve this, the project will invest in three specialized cores, along with an Administrative Core. The project will support a Research Support Core to provide high-quality research translation, strengthen data infrastructure, connectivity, and networking capabilities through strategic investments in cyber, human, and physical infrastructure. The STEM Pathways K-16 Core aims to strengthen and broaden participation in Delaware's STEM pipeline and related pathways. The Workforce Development Core will focus on strengthening skills and broadening participation in STEM through investments in team building, research collaboration, and connectivity to meet the needs of employers in the state's priority areas. In addition, an Administrative Core will support overall cohesion, facilitate research and infrastructure collaborations, communicate opportunities and enhance and sustain jurisdiction-wide research administration. These investments will make Delaware an ideal testbed to implement E-CORE's mission to promote sustainable improvements in the research infrastructure and R&D capacity and competitiveness. This project is supported by the EPSCoR Research Infrastructure Improvement Program: EPSCoR Collaborations for Optimizing Research Ecosystems (E-CORE). E-CORE supports jurisdictions in strengthening their jurisdiction-wide research ecosystems through fostering interconnected networks, building research infrastructure, and growing research capacity and competitiveness aligned with jurisdictional priorities. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

One of the largest pools of actively cycling carbon is the organic carbon dissolved in deep-ocean seawater. However, the sources and sinks of organic matter associated with this pool of carbon are not well-understood. This project will investigate organic carbon cycling processes that occur as seawater flows through oceanic crust at low temperatures. A large volume of seawater flows through cool ocean crust as it ages, but these sites are not well-studied. Unlike hydrothermal vent fluids, low temperature seeps are difficult to identify because the temperature and chemistry of bottom seawater and cool crustal fluids are more similar. This makes it difficult to find these sites at the seafloor, leaving them largely unexplored. This study will measure the concentration and composition of dissolved organic matter in fluids from two newly discovered sites where low-temperature fluids discharge from seamounts. In addition, the research will provide new tools for organic matter characterization. As a result, this project will illuminate a part of the oceanic carbon cycle that has often been overlooked. This project also aims to inspire an interest in chemistry and biology among K-12 students by bringing the deep ocean to them. Teachers will develop classroom materials that introduce students to the charismatic octopus families that are attracted to sites of natural fluid discharge, and the fluid chemistry that shapes their behavior, during professional development workshops. The project will also engage students from primarily undergraduate institutions in deep-ocean research. Undergraduate and graduate students at the University of Delaware will also be involved in the project. The scientific objectives of this 5-year project are to: (1) expand the view of cool, aging crust from one study site (North Pond IODP (International Ocean Discovery Program) Site) to three by following the lead of brooding octopus mothers which have recently been found clustered around sites of moderately warm natural discharge from the Dorado and Davidson Seamounts; (2) broaden the analytical window for dissolved organic matter characterization to better identify signatures of microbial activity; and (3) refine the present global estimate of organic carbon loss from the deep ocean by crustal processes. In addition, societal benefits of the project include educational and learning activities for students from the K-12 to the graduate level that are well-integrated with the research. The project will provide training for one graduate student and more than 10 undergraduate students, half of which will come from primarily undergraduate institutions. This project also includes workshops for 30 STEM teachers over 3 years emphasizing hands-on activities that will bring environmental chemistry lessons aligned with Next Generation Science Standards into K-12 classrooms in the State of Delaware. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

This doctoral dissertation project examines the extent to which flooding can result in increased disease risks for human populations, particularly when parasitic diseases are transmitted via organisms that live in bodies of water near human communities. This multifaceted project examines the ways that the distributions of parasites and their hosts align with the geographical distribution of extreme hydrological events. Concurrently, the researchers examine heterogeneity in human communities that may be associated with the risk of parasitic infections during floods. By combining these data sources, the researchers advance a general conceptual model for the transmission of parasitic infections. Key findings are shared with local community partners, and the project contributes to the education and training of an early-career scientist. This project considers human variability to parasitic infections in response to both environmental factors, especially hydrological events, and variation in human populations. Adopting a biogeographical approach, the researchers examine the distribution of vector species over time while concurrently leveraging machine learning methods to identify the considerations that underlie vulnerability. As a complement to the quantitative modeling, the researchers employ focus groups to substantiate the mechanisms that underlie disease transmission and potential remedies. The project contributes to scholarship in geography, water resource engineering, and public health. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2025-03

PROJECT SUMMARY Candidate: Dr. Hast received his bachelor's degree in mechanical engineering with a focus on thermodynamics and a Ph.D. in mechanical engineering with a focus on computational biomechanics. His long-term goal is to become an independent researcher focused on improving patient outcomes following fragility fractures. This proposal uses an interdisciplinary research framework using a small animal model to identify mechanisms that govern fracture healing in healthy and diseased bone. The objective of this proposal is to have Dr. Hast acquire the training necessary in small animal models, cellular assays, and molecular laboratory techniques to fully define the mechanisms that govern callus formation and bone remodeling in the milieu of osteoporosis. This will equip him with the tools necessary to become a thought leader in the field of fragility fracture repair. Mentoring Committee and Training Plan: Dr. Mauck will serve as primary mentor and provide structured mentoring in tissue engineering, laboratory techniques, and provide career development training. Drs. Boerckel and Qin will serve as co-mentors and provide hands-on training in small animal surgeries, histology, immunohistochemistry, and molecular profiling. Dr. Hast will also have advisory committees (technical: Drs. Liu, Ahn, Mehta, Manogharan; career: Drs. Soslowsky, Arbogast, Elliott) to guide his development. Dr. Hast will participate regularly in faculty meetings, seminars, workshops, and coursework to make him a complete and independent researcher. He will present his research at national conferences and in peer-reviewed journals. Environment: The University of Pennsylvania is home to the McKay Orthopaedic Research Laboratory and Penn Center for Musculoskeletal Disorders (PCMD), a 22,00 ft2 research space that is well-equipped for the proposed training and research plan. The PCMD and hosts several NIH supported core services focused on musculoskeletal research, which include histology, biomechanics, and imaging. Both the PCMD and Penn host weekly/monthly seminars in cellular and molecular biology, medical imaging, bioengineering, and professional development. Research: This proposed work will challenge the current clinical paradigms that use metal implants to heal fractures. The central hypothesis is that properly timed gradual (gradient-based) increases in loading will lead to improved repair of simulated fractures. To test this novel hypothesis, a rat model will be used in 2 aims. Aim 1 will establish the effects of gradual introduction of mechanotransduction on fracture repair in healthy bone. Aim 2 will determine what changes in mechanotransduction are required to improve fracture repair in compromised bone. Testing these aims will generate critical preliminary data for a follow-up R01 that includes a larger animal model, along with pharmacological interventions that may accelerate and improve repair. Institutional Commitment to Candidate: Dr. Hast is an Assistant Research Professor and has been provided start-up funds, laboratory space, and research personnel needed to perform the proposed work.

NSF Awards · FY 2025 · 2025-03

NONTECHNICAL SUMMARY This award supports theoretical research and educational activities aimed at understanding quantum magnetic materials. Today's information technologies utilize the electron charge as the primary carrier of information. However, the electron also carries a tiny angular momentum called spin that enables spintronics, which is the spin-based counterpart of familiar electronics. Two key phenomena in contemporary spintronics research are the spin-transfer torque, where flowing electrons interact with local magnetization in a material, and spin pumping, where a varying local magnetization generates a spin current. Spin-transfer torque underlies a host of novel technologies, such as magnetic random access memories that are already commercially available, and neuromorphic circuits for hardware-based artificial intelligence. Even though spintronic phenomena are fundamentally quantum in nature, the standard microscopic understanding of both spin torque and spin pumping is essentially a quantum-classical hybrid: Flowing electrons are treated quantum-mechanically while localized spins are treated as classical objects. This heretofore necessary simplification results in a number of unsolved puzzles when one tries to explain certain spintronic experiments. These puzzles can be traced to quantum effects where quantum entanglement stands out. Entanglement is one of the most remarkable features of the quantum world whereby in a system of just two entangled quantum particles (e.g., two electron spins) what happens to one of them instantaneously determines what happens to the other one, even if they are arbitrarily far away from each other. The overarching goal of this project is to open new avenues for spintronics by bringing entanglement effects into the realm of spin-torque and spin-pumping phenomena. In turn, and in addition to resolving existing puzzles, this will make it possible to design novel protocols for probing quantum magnetic materials via the extensive toolbox of experimental techniques developed for spintronics over the past three decades. In addition to the development of theoretical methods and open-source software for modeling spin transport in quantum materials, the project will also include advanced training for graduate students, preparing them for a productive participation in the nation's quantum workforce. The project will also provide opportunities for high-school students from Delaware and neighboring states to work on magnetism research projects and prepare them for competitions in math, science, and technology. TECHNICAL SUMMARY The dynamics of localized spins within magnets in contemporary spintronics, driven out of equilibrium by injecting current or by applying external fields, relies on the celebrated Landau-Lifshitz-Gilbert (LLG) equation that considers their local magnetization as a classical vector. The applicability of the LLG equation demands that the underlying quantum state of localized spins must remain unentangled. However, several experiments in spintronics involving particular antiferromagnetic layers cannot be explained by LLG dynamics. This suggests the presence of mixed entangled quantum states of many spins within nonequilibrium antiferromagnets, despite their interaction with the inevitable dissipative environment. The project will develop theories to explain experimental puzzles in antiferromagnetic spintronics, as well as in current-driven atomic and molecular spins on surfaces as a smaller version of quantum spin systems that can serve as testbed for new method development. These predictions can then be exploited to design experiments where spin torque and spin pumping are used to probe exotic magnetic quantum matter. Such matter notably includes quantum spin liquids, characterized by long-range entanglement and fractionalized excitations, whose confirmation and control is highly sought as a resource for topological quantum computing. The theory developed in this project will also guide experiments toward direct quantification of entanglement of antiferromagnets or quantum spin liquids, but via table-top experiments suitable for two-dimensional and/or nonequilibrium materials where neutron scattering becomes inapplicable. These activities will require construction of new theoretical methods to study the fundamental problem of quantum transport of spin and charge in strongly interacting boundary-driven systems that are coupled to different baths at their edges. In addition to the development of theoretical methods and open-source software for modeling spin transport in quantum materials, the project will also include advanced training for graduate students, preparing them for a productive participation in the nation's quantum workforce. The project will also provide opportunities for high-school students from Delaware and neighboring states to work on magnetism research projects and prepare them for competitions in math, science, and technology. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

Autonomous driving is the much-anticipated transformative technology to revolutionize conventional human driving toward full automation, high safety, and versatile intelligence. In pilot commercialization efforts (e.g., Waymo), autonomous vehicles rely on onboard sensors, hardware, and AI-based software to perceive, understand, and react to complex surrounding environments. Existing autonomous vehicles are manufactured under tightly coupled hardware and software, with limited future upgradability throughout their life cycles. This project’s novelty is to advance existing autonomous driving by integrating the available information from proximate vehicles and roadside infrastructures to seamlessly incorporate into the autonomous driving software, substantially improving driving performance and safety. The project's broader significance is empowering existing vehicles with ever-evolving autonomous driving capability and continual upgradability. Furthermore, the project involves cyber workforce training activities and industry collaboration. This project aims to democratize autonomous driving technologies to every connected vehicle via designing a new connected autonomous driving as a service (CADaaS) paradigm. The fundamental idea is to enable adaptive vehicle-edge collaboration to obtain the latest autonomous driving stacks, including perception, prediction, and planning. First, new network threading techniques are designed to achieve user-initialized resource reservation and user-grained performance assurance in the wireless network. Second, new deadline-aware inference frameworks are designed to assure the percentile constraint of inference latency under multiple deep neural networks (DNN) concurrency in the edge server. Third, CADaaS is deployed and evaluated under real-world at-scale network and computing scenarios, including the University of Nebraska-Lincoln Husker-Net and the University of Delaware D-STAR. This project is transformative in defining, reshaping, and catalyzing the on-the-horizon connected autonomous driving technology, software-defined vehicles, and vehicle computing paradigm. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

There are two common versions of carbon in carbon dioxide, carbon-13 and carbon-12. The ratio of carbon-13 to carbon-12 (13C/12C) in petroleum is very different from that ratio in seawater. One of the most sensitive ways we have of finding petroleum-based carbon in the ocean is by looking for changes in 13C/12C of carbon dioxide dissolved in seawater. Unfortunately, this is seldom done because 13C/12C measurements are expensive and not regularly done at sea. In this project, the 13C/12C ratio of ocean carbon dioxide will be measured in the Pacific and Indian Oceans using a new instrument that is much less expensive to run and can run many more samples than previous methods. The new measurements will be compared to old ones in order to estimate how much man-made carbon dioxide has entered the ocean. In coming decades changes in ocean behavior should be detectable by comparison with the data collected in this project. PIs have developed a seagoing dissolved inorganic carbon (DIC) extraction system coupled with a laser spectrometer that can be deployed at sea. The combination can provide unprecedented coverage and state-of-the-art precision and accuracy for 13C/12C of DIC. The project centers on instrument deployment, with personnel, on 3 cruise legs along a meridional line in the Pacific Ocean and on one meridional cruise in the Indian Ocean. The data will be compared with prior datasets using established statistical techniques to quantify decadal changes in 13C, providing a powerful window into upper ocean turnover and anthropogenic CO2 uptake rates. The project supports a graduate student over the four-year duration of the project and a postdoctoral scholar for 2.5 years. Both will participate and be trained in collection and analysis of the 13C datasets. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

This Faculty Early Career Development (CAREER) award will support research that intends to advance fundamental understanding of how cells and tissue communicate information about their mechanical environment. Changes in the mechanics of tissues can occur locally in disease, such as stiffening of the tissue after myocardial infarction or wounds in other tissues. Importantly, the impact of local stiffening can spread after injury causing fibrosis, which can interfere with normal function. There is a gap in knowledge surrounding the mechanisms of this mechanobiological spread in space and time and closing this gap can inform new strategies to treat disease. This research project intends to develop new platforms based on magnetic materials that can be locally stiffened in time with precise control over location to mimic different biological events. This project will use experiments to explore how far, how fast, and through what channels this local stiffening is spread through surrounding cells. The research objectives of this project are coupled with educational objectives that seek to stimulate knowledge and interest in STEM. This will be accomplished through the development of captivating board games that teach mechanobiology principles and involvement of the local community through an afterschool science program. The overarching goal of this research is to understand how mechanobiological signaling is transduced via communication between cells away from a region of local stiffness change and matrix-cell signaling. The project intends to develop material platforms with the ability to change their local stiffness dynamically via the application of a magnetic field. Experiments locally manipulating the stiffness and measuring the mechanoresponses away from the local area will be performed with varying size, strength, duration, and rate of stiffening to measure the distance and speed signaling travels. The mechanobiological pathway governing how matrix-cell signaling influences cell-cell signaling over space and time will be interrogated via controlled inhibition experiments to reveal fundamental mechanisms. Experiments will be performed with both 2D and 3D models to consider the role of increased tissue complexity in this signaling pathway. If successful, this project will introduce a new class of tools that can provide unique insight into spatiotemporal mechanobiology and significantly advance our understanding of dynamic biological processes including wound healing or myocardial infarction. This project is jointly funded by Biomechanics and Mechanobiology (BMMB) Program in the Division of Civil, Mechanical, and Manufacturing Innovation (CMMI) and the Established Program to Stimulate Competitive Research (EPSCoR). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-01

The University of Delaware's College of Earth, Ocean and Environment (CEOE) in Lewes, DE will host a Research Experience for Undergraduates (REU) Site program. The program will bring ten undergraduates to UD’s Lewes campus each summer for three years to conduct independent ocean science research with the guidance of a research mentor. The main focus of the program is to train students in the process of doing science including such skills as formulation of research questions, research methods and design, and problem solving. Interns will also participate in professional development workshops on topics ranging from science ethics, to science communication, to grad school funding. They will join several field trips including a half-day aboard the R/V Daiber, a marsh walk, and a daylong trip to Cape May to join the Rutgers REU program to learn about aquaculture practices and careers. At the end of the summer, interns will be encouraged to apply to the CEOE graduate program and considered for a graduate fellowship. This program will provide a total of thirty undergraduates with extensive research experience and career training. The site has state of the art research facilities, excellent mentors and access to the local coastal environment. Potential research topics include a wide breadth of ocean science ranging from microbial ecology, to paleoceanography, to comparative physiology and behavior of marine animals to biogeochemistry and physical oceanography, in addition to other topics. Professional development opportunities for interns will complement research training and will address career options, paying for graduate school, and more. The program will continue collaborations with Delaware Technical Community College and Delaware State University. This project is jointly funded by the Division of Ocean Sciences and the Established Program to Stimulate Competitive Research (EPSCoR). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-01

The shift from fossil fuels to biomass (e.g., crops) for renewable energy and valuable chemicals has broad support from both government agencies and the scientific community. However, current biomass conversion techniques, which depend on thermocatalysis, are energy-intensive due to the need for high temperatures and pressures. Conversion using electricity (electrocatalysis) is a more sustainable approach but requires better understanding of the mechanisms involve as well as stable catalyst. This NSF EPSCoR Research Fellows project combines catalysts development expertise from the University of Delaware with electrocatalysis experts at the Renewable & Sustainable Energy Institute at the University of Colorado to advance the fundamental understanding of biomass conversion. With the use of specialized techniques, the effect of the catalyst shape and size, as well as the chemical environment (electrolyte) can be interrogated in real time as the reactions are happening. This level of insight will help design more efficient and stable catalysts not only for biomass conversion but also for conversion of CO2 and hydrogen production. This fellowship will support an early-career PI in establishing and sustaining a multidisciplinary research program. It will also provide educational opportunities and hands-on experience to undergraduate and graduate students in the areas of renewable energy and sustainability. This Research Infrastructure Improvement EPSCoR Research Fellows project would provide a fellowship to an Assistant Professor and training for a graduate student at the University of Delaware. Electrocatalysis has been identified as green, viable method for the up-conversion of biomass compounds. However, there are still challenges that need to be addressed with regards to catalyst efficiency, selectivity, stability, as well as knowledge gaps on the conversion mechanisms. The overall objective of the proposed research is to develop efficient, selective, and stable catalysts for electro-conversion of furanic compounds via understanding of structure-activity-mechanism relationships. The central hypothesis is that the activity and selectivity can be modulated by the size/shape of nanocrystals-based electrodes and spectator ions in the electrolyte. The hypothesis will be validated in collaboration with researchers at the Renewable & Sustainable Energy Institute at the University of Colorado. Through this collaboration, mechanistic insights will be gained employing the specialized techniques of in situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) and differential electrochemical mass spectrometry (DEMS). The results from this work are poised to bridge knowledge gaps in the field of electrocatalytic biomass conversion, provide insight into the interplay between the electrode-electrolyte interface, and advance the development of effective catalysts. In addition to the innovative research, this fellowship will allow the early-career PI to gain access to and training on ATR-SEIRAS and DEMS which will be transformative for the PI’s research program and the institution. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-01

PROJECT SUMMARY/ABSTRACT A recent emphasis in stroke rehabilitation research focuses on capturing how an individual’s paretic arm capacity (what one can do when prompted in the clinic) compares to an individual’s daily performance (what one does spontaneously in the real-world). Historically, motor capacity and performance after stroke have been considered congruent. However, recent work has demonstrated that motor capacity and performance are not equal at various time points of stroke rehabilitation. In fact, we often see improvements in capacity with stroke rehabilitation, but fail to observe comparable improvements in real-world performance. Learned non-use is the phenomenon describing the incongruence between capacity and performance, which can have detrimental effects on full recovery. For example, an individual may show improved outcomes on an in-clinic upper extremity assessment (i.e., Fugl Meyer) thereby able to be discharged from outpatient rehabilitation services, but rarely use their arm in daily life despite their increased ability. Decreased real-world usage can lead to a cycle of disuse, which can plateau or negatively affect recovery. Previous animal studies have used a limb deafferentation model that eliminates sensory information to study learned non-use. This deafferentation model eliminates proprioception, the sense of body position and movement in space, but does not affect motor function. This work showed that animals significantly decreased spontaneous use of the arm when proprioception was eliminated regardless of continued motor capacity. Despite an established connection in animal models, there is a critical gap to understand the connection between proprioception and learned non-use in individuals with stroke. The overall objective of this proposal is to evaluate the relationship between proprioceptive impairment and learned non-use– which accounts for both paretic arm capacity and performance. Our central hypothesis is that proprioceptive impairments of the upper limb will have a negative effect on paretic arm capacity, performance, and, subsequently, learned non-use. In Aim 1, we will identify the contributions of proprioception on paretic arm capacity, using both clinical and laboratory measures. In Aim 2, we will understand the moderating effects of proprioception on learned non-use, using a self-report clinical measure and activity monitors to capture real- world paretic arm performance. We anticipate that stroke participants with proprioceptive deficits will have lower capacity to utilize the paretic arm. Additionally, we anticipate that proprioception is a moderator of learned non- use, accounting for the innate relationship between capacity and performance. Completion of this proposal will provide greater knowledge about proprioception as a potential mechanism underlying learned non-use after stroke. Without this knowledge, typical interventions used for learned non-use may not be effective because they address only the behavioral consequences of a potentially underlying sensory deficit. The overall impact of this proposed research lies in understanding how proprioceptive deficits contribute to paretic arm activity– consisting of both in-clinic capacity and real-world performance.

NSF Awards · FY 2025 · 2025-01

This project provides funding for the Research Vessel Hugh Sharp to conduct oceanographic research missions supported by the National Science Foundation. The oceanographic research vessels of the Academic Research Fleet (ARF), operated by the academic institutions within the University-National Oceanographic Laboratory System (UNOLS) framework are multi-use facilities used to expand knowledge of the ocean environment. The surface work of these ships is complemented by human-occupied, remotely operated, and autonomous undersea vehicles and sensors that provide vital tools to understand the oceans and their resources. These seagoing research and educational facilities enable scientists and students to study natural phenomena and train future scientists while on board state-of-the-art oceanographic research vessels utilizing high-quality instrumentation. The ship operators will also conduct learning activities for students and the general public including hands-on demonstrations of marine science research guided by faculty, students and ship crew members. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-01

Phytoplankton help regulate climate and provide many important ecosystem services. This project will investigate changes to phytoplankton community composition using space satellite data. Hyperspectral images from space satellites will provide a large-scale view of coasts and estuaries. Phytoplankton absorb and scatter light in distinct ways, which hyperspectral images can capture. Analysis of these images by using artificial intelligence with hyperspectral remote sensing, will reveal many details about the composition of the phytoplankton community. The project will develop an open, large-scale database of phytoplankton observations. The first foundation models for plankton community structure will be built. New software toolkits in artificial intelligence will be developed and shared with the research community. The findings will be integrated into instructional materials. Undergraduate and graduate students, particularly those from under-represented groups, will be engaged in the research. This project will explore the basic mechanisms and impacts of climatic factors on phytoplankton community composition in order to gain a better understanding of food web structure, higher trophic level production, and biological shifts at regional-to-global levels. This project will address longstanding challenges for ocean color remote sensing applications, through characterizing phytoplankton communities in coastal waters by developing artificial intelligence methods to handle hyperspectral remote sensing data. This project will be organized around three main goals. First, address scarcity of in situ data for estuarine-coastal phytoplankton community compositions by constructing a large-scale database for phytoplankton observations, enabling global data sharing and contribution. Second, build a large foundation model tailored to phytoplankton community composition and artificial intelligence-based methods for predicting change in the phytoplankton community. New software tools for hyperspectral imagery using artificial intelligence will be developed and shared with the plankton and coastal oceanographic research community. Third, use artificial intelligence to address spatial-spectral-temporal variations in phytoplankton community composition. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-01

Lens developmental defects result in cataract. Thus, it is critical to define the proteins and the mechanisms that mediate regulatory control in lens development. Toward this goal, we developed a bioinformatics resource iSyTE (integrated Systems Tool for Eye gene discovery) and predicted that the small Maf transcription factors (TFs) Mafg and Mafk are significantly expressed in the lens and are necessary for its development and transparency. Because Mafg and Mafk can bind the cis-regulatory sites bound by the human cataract-linked gene c-Maf, and because their binding is influenced by other co-regulator partners like Nrf2, the investigation of these unexamined small Mafs in the lens is critical for understanding the role of Maf-family TFs in cataract. In support of iSyTE’s prediction, we find Mafg-/-:Mafk-/- double knockout (Mafg/kDKO) mice show embryonic-onset lens developmental defects, exhibiting abnormalities in lens epithelium and fiber cells. Moreover, our data shows that when one of the wild-type Mafk alleles is retained in a homozygous Mafg KO background, as in Mafg-/-:Mafk+/- compound KO (Mafg/kCPKO), this rescues the embryonic lens defects but results in adult cataract. We also find mice null for the small Maf coregulator TF, Nrf2, exhibit cataract. These data indicate a role for Mafg, Mafk and Nrf2 in lens transcriptional control. In support of this, bulk RNA-seq on Mafg/kDKO lenses identifies a cohort of differentially expressed transcripts, among which are genes relevant to lens cell biology, and whose deficiency causes human cataract, as well as novel candidates that can advance our knowledge on the mechanisms in lens development. Further, microarray profiling of Mafg/kCPKO lenses prior to cataract also identifies misexpression of genes relevant to lens biology. Thus, Mafg/kDKO and Mafg/kCPKO mice, along with Nrf2cKO, present novel models to examine small Maf-based control mechanisms in the lens and their impact on c-Maf’s function. Thus, this proposal addresses the hypothesis that Mafg, Mafk and their co-regulators mediate key lens transcriptional control that also impacts c-Maf function in the lens. This will be tested as follows. (Aim 1) Characterize Mafg/kDKO, Mafg/kCPKO and Nrf2cKO mice to define the etiology of the lens cellular defects and cataract. (Aim 2) Gain insights into the molecular underpinnings of the lens defects by performing multiomics single nuclei (sn)RNA-seq to identify cell-specific transcriptome alterations in Mafg/kDKO, Mafg/kCPKO, c-MafKO and Nrf2cKO lenses. Additionally, perform snATAC- seq to identify lens cell-specific chromatin accessibility changes. (Aim 3) Elucidate the direct genomic targets of for Mafg, Mafk, c-Maf and Nrf2 in the lens by chromatin immunoprecipitation followed by sequencing (ChIP-seq) on wild-type mouse lenses. Further, investigate high-priority Mafg and Mafk lens targets by reporter assays. Finally, analyze these Mafg, Mafk, c-Maf and Nrf2 regulatory data within the larger context of the existing lens regulatory data to derive Maf downstream gene regulatory networks (GRNs) in the lens. The impact of this innovative proposal is: it will characterize small Maf-transcriptional control in the lens, uncover its functional connectivity with Nrf2 and the human cataract-linked TF, c-Maf, and define lens pathology at cellular resolution.

NSF Awards · FY 2024 · 2024-12

The objective of this EArly-concept Grant for Exploratory Research (EAGER) project is to support research on developing an open source, AI-enabled synthetic population inventory. Such an inventory facilitates disaster impact studies by eliminating the need for complex data generation and downstream simulation tasks to generate behavior insights. A comprehensive and accurate synthetic population dataset that integrates people, the built environment, and behavior plays a critical role in disaster impact assessment. The resulting inventory serves as a crucial data source for training and testing resilience tools as well as informing disaster policies. The advancements in knowledge, models, and algorithms from this project lay the groundwork for leveraging generative AI and multi-domain data fusion to generate synthetic data. This research project puts forward a novel, untested paradigm for synthetic population generation. A new generative AI framework is introduced to learn intricate patterns in microdata to produce diverse and realistic synthetic populations. Explicit household and building relationships are also revealed through machine learning applied to language-embedded household and building features. The project deepens understanding of post-disaster household adaptation through comprehensive surveys and data fusion with large language models. This paradigm has the potential to transform how synthetic populations are used in various fields, making disaster planning and policy development more effective and accessible. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-11

PROJECT SUMMARY Cardiovascular disease (CVD) morbidity has increased by up to 30% in midlife women in the last 20 years. Increased CVD risk in midlife women is at least partially explained by declines in estradiol (E2) that occur across the menopausal transition and accelerate vascular aging. Although vascular dysfunction has been noted in early perimenopausal women, our novel preliminary data show that reductions in endothelium-dependent dilation are evident in some premenopausal midlife women, strongly suggesting that the development of endothelial dysfunction in midlife precedes the menopausal transition and thus cannot be solely explained by the loss of E2. Emerging factors that may help explain accelerated vascular aging in midlife women include greater emotional responsivity to daily stressors and greater sleep irregularity. While both common features of menopause, these dynamic constructs can vary across the menopausal transition and are independently related to disruptions in vascular homeostasis. As such, amplified emotional responsivity to daily stressors and greater sleep variability may represent novel, modifiable, biobehavioral mechanisms to help explain the inter-individual variability in the degree of vascular endothelial dysfunction in premenopausal midlife women. The objective of this proposal is to test the central hypothesis that (a) greater negative affective responsivity to daily stressors and (b) greater sleep variability will each be related to more severe declines in endothelial function in premenopausal midlife women and that these associations will be magnified during E2 suppression (simulated menopause) compared to during natural cycling. To test this, 30 pre- menopausal middle-aged women (45-55 years) will complete two ‘measurement bursts’ (randomized, crossover): one while naturally cycling and one during simulated menopause using an ovarian hormone suppression intervention [daily subcutaneous injections of a gonadotropin-releasing hormone antagonist (GnRHant; Ganirelix acetate)]. On days 1-10 of each burst, we will assess multiple dynamic aspects of daily stress processes (mobile app-based daily diary approach) and sleep health (wrist accelerometry). On days 0 and 11 (i.e., pre and post), we will use orthogonal laboratory-based techniques to examine the mechanistic regulation of microvascular endothelial function (intradermal microdialysis coupled with laser Doppler flowmetry), an approach that allows for a detailed characterization of vascular endothelial function. This multipronged, multidimensional framework will allow for a comprehensive examination of behavioral and physiological factors in the context of aging and changes in reproductive hormones to better understand subclinical CVD risk in midlife women—a priority of the Trans-NIH Strategic Plan for Women’s Health Research. The anticipated outcomes will provide proof of concept that emotional responsivity to daily stressors and sleep health are potentially potent, modifiable mechanisms contributing to inter-individual heterogeneity in vascular dysfunction in midlife women. As such, this line of inquiry is uniquely poised to inform subsequent, larger and fully powered trials to test the effects of behavioral (i.e., stress reduction, improved sleep) and/or pharmacological (i.e., hormone intervention) strategies to preserve vascular health during menopause, thereby mitigating CVD risk.