University Of Iowa

NIH Research Projects · FY 2024 · 2024-09

Project Summary More than 20% of oral squamous cell carcinoma (OSCC) patients present with bone invasion and require maxillary/mandibular continuity restoration after tumor excision. Postoperative adjuvant radiotherapy or chemoradiotherapy is also needed for advanced OSCC tumors. However, despite standard-of-care treatments, the 5-year survival rate for advanced-stage OSCC is less than 50%. Notably, adverse effects of radiotherapy can impair bone formation and delay graft osseointegration after reconstructive surgery. Patients receiving adjuvant radiotherapy have an approximately 20% long-term failure rate because of nonunion of bone grafts, hardware infection, and ultimately flap malunion and loss. Thus, a safer and more effective therapeutic with strong osteoinduction and anti-OSCC capacities are needed to improve reconstructive surgery outcomes of OSCC treatments. MicroRNAs (miRs) are small non-coding RNAs that play crucial roles in craniofacial bone metabolism and OSCC initiation and progression via epigenetically regulating cellular biological processes. miRs have emerged as a potential tool to improve OSCC treatment and reconstructive bone regeneration. Our previously funded studies have demonstrated that miR-200c targets many proinflammatory cytokines and osteoclastogenic mediators and effectively attenuates inflammation and bone resorption. Local application of plasmid DNA (pDNA) encoding miR-200c also significantly promotes osteogenic differentiation of hBMSC and bone regeneration by activating Wnt and BMP activities. pDNA miR-200c incorporated into 3D-printed scaffolds or delivered by CaCO3-based nanoparticles effectively enhance bone regeneration at calvarial and maxillary defects. In addition, our preliminary studies have identified that radiation in OSCC patients and rat mandibles suppress miR-218 expression, a miRNA similar to miR-200c that potently suppresses OSCC and osteoclastogenesis and promotes bone regeneration. Therefore, we hypothesize that pDNA encoding miR- 200c and miR-218 delivered by CaCO3 will promote bone regeneration and bone graft integration in irradiated mandibular bone defects by improving osteogenesis and mitigating inflammation and osteoclastogenesis. We propose to determine the functions of miR-200c in promoting mandibular bone regeneration under radiation and preventing bone graft resorption (Aim 1) and the additional/synergistic function of miR-218 in miR-200c- mediated bone regeneration (Aim 2). We will also elucidate the molecular mechanism(s) and cellular effects underlying anti-OSCC radiation and osteoinductive miRNAs (Aim 3). After accomplishing the project, we expect to lay the groundwork for developing a novel miRNA-based therapeutic that will enhance osteoinduction and suppress bone resorption for advanced OSCC patients.

NIH Research Projects · FY 2024 · 2024-09

Project Summary Given the importance of oncogenic epidermal growth factor receptor (EGFR) signaling for tumor cell proliferation in head and neck squamous cell carcinoma (HNSCC), we believe that EGFR inhibition remains worthy as a strategy to be included in radiotherapy (RT) protocols for HNSCC and that further investigation of mechanisms responsible for poor response to EGFRIs is warranted. Based on our preliminary data, we propose that increased interleukin-1 (IL-1) signaling may lead to sustained interleukin-8 (IL-8) signaling and NADPH oxidase 2 (NOX2)-derived superoxide (O2.-) production which is associated with pro-survival signaling and an immunosuppressive tumor microenvironment leading to poor response to EGFRIs. As a result, targeting the IL-1 signaling pathway may enhance HNSCC tumor response to EGFRIs combined with RT. The overall hypothesis of this grant application is that NOX2 redox activity and IL-8 signaling contribute to poor long-term anti-tumor response to EGFRIs via increased IL-1 signaling in RT-treated HNSCC tumors. Aim 1 will determine if IL-1-mediated NOX2 redox activity is involved in poor HNSCC tumor response to RT+EGFRIs; Aim 2 will determine if IL-1-mediated IL-8 signaling is involved in poor HNSCC tumor response to RT+EGFRIs; and Aim 3 will determine if inhibition of IL-1 signaling would enhance HNSCC tumor response to RT+EGFRIs. Overall, we expect that this application will highlight novel redox mechanisms associated with poor response to EGFRIs and possibly lead to promising new therapeutic approaches for RT-treated HNSCC patients.

NSF Awards · FY 2024 · 2024-09

Many agricultural, farming, and industrial processes release excess nitrate into the environment, making it the most pervasive groundwater pollutant in the world. This poses a serious threat to human and ecosystem health. Capturing and converting low nitrate concentrations from groundwater and surface waters is exceptionally challenging. To address this pressing need for nitrate management across food and water systems, this project will bring together experts from various complementary disciplines to develop an integrated nitrate capture and conversion device that is efficient, low-cost, and powered by renewable resources. The device will use light energy to concentrate nitrate from waste streams (photocapacitive concentration) and electrically-driven chemical reactions (electrocatalytic conversion) to produce nitrogen and valuable chemicals such as ammonia. This approach will provide insights into the chemical, physical, and catalytic processes involved in nitrate concentration and conversion, as well as the socioeconomic factors that limit the adoption of nitrogen management technologies. The project outcomes will advance the design of sustainable resource recovery systems to manage the nitrogen cycle and may reduce the cost of nitrate treatment. Further, this research will empower resource-limited communities and industrial point source treatment operators to better address their nitrate water treatment needs. Graduate and undergraduate students at the University of Michigan, the University of Iowa, and the University of Texas at Austin will receive interdisciplinary technical training. The planned outreach activities will also provide opportunities to broaden the participation of underserved groups in STEM. This project aims to develop an integrated photocapacitive concentration and electrocatalytic conversion technology for nitrate treatment. The project includes four research thrusts focused on developing and understanding this nitrate treatment technology. The first thrust advances the discovery and design of selective photocapacitive systems to capture and concentrate nitrate. In the second thrust, the team will develop and test electrocatalysts made from inexpensive and earth-abundant elements that are durable and thermodynamically and kinetically compatible for nitrate capture and conversion to ammonia or nitrogen. The third thrust involves physics-based modeling and testing of the transport processes needed to optimize the photocapacitive capture and electrocatalytic conversion system. The fourth thrust assesses process sustainability using technoeconomic and life cycle analyses to promote technology adoption by impacted communities. By integrating photocapacitive and electrocatalytic tools, this project will create a technology platform that sustainably captures and transforms nitrate, a regulated human health risk, into useful products. This convergent research advances knowledge by simultaneously considering nitrate concentration and conversion, unlike existing studies that separate these steps. The project’s outreach activities include (1) creating an exchange program for interdisciplinary summer undergraduate research experiences to prepare students from underrepresented groups for graduate research; (2) engaging water treatment professionals and communities in Iowa and Texas who are working to address nitrate pollution; and (3) integrating best practices from NSF Research Traineeship programs focused on innovations at the nexus of food-energy-water systems. 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 · 2024-09

PROJECT SUMMARY Several lifestyle and genetic major risk factors for age-related macular degeneration (AMD) are generally associated with increases in extracellular matrix (ECM) stiffness. In other tissue systems, changes in ECM stiffness are known to elicit pathological epithelial-to-mesenchymal transition (EMT), in which once- mature cells de-specialize and transform to a proliferative, migratory, and fibrotic phenotype. EMT of retinal pigmented epithelial (RPE) and choroidal endothelial cells (ChECs) is acknowledged as a hallmark of AMD, but the relationships between AMD risk factors and EMT remain unknown. To better understand and treat AMD, there is a critical need to determine how RPE and ChECs respond to changes in ECM stiffness. In this application, the overall objective is to determine how matrix biomechanics impact RPE and ChEC fate using in vitro and ex vivo models of tissue stiffening. The central hypothesis is that matrix stiffening plays a role in chorioretinal EMT by activation of mechanical transduction signaling pathways. The rationale for the proposed research is that detailed understanding of the role tissue stiffening plays in AMD progression is likely to provide a solid foundation upon which to base the development of preclinical interventions targeting druggable signaling pathways for treatment of early AMD. Two specific aims will be used to test the central hypothesis. Aim 1: determine how matrix stiffening impacts RPE and ChEC EMT in vitro. Human induced pluripotent stem cells (iPSCs), including some from donors with high-risk ARMS2/HTRA1 polymorphisms, will be differentiated to RPE and ChECs and seeded on hydrogels that match the stiffness of the RPE/choroid tissue complex. Step changes in matrix stiffness that correspond to moderate and advanced aging will be instigated using in situ photocrosslinking. Migration, proliferation, loss of RPE and ChEC markers, gain of mesenchymal markers, activation of mechanical transduction pathways will be characterized. Aim 2: demonstrate that matrix stiffening leads to chorioretinal tissue EMT ex vivo. Porcine RPE/choroid tissue will be used to create an ex vivo model of tissue stiffening via photocrosslinking and subsequent tissue culture with or without exogenous HTRA1. Human donor RPE/choroid tissue (AMD and age-matched controls) will also be evaluated. For all tissue types, spatial stiffness maps will be created using atomic force microscopy, with simultaneous imaging of EMT protein localization. The proposed research is innovative because it uses new approaches to in situ matrix stiffening, focuses on matrix stiffness as a possible contributor to AMD pathophysiology, and explores the interplay between genetic risk factors and EMT. The primary expected outcome of the proposed research is a detailed understanding of the intersections between matrix stiffness, genetic risk, and EMT of RPE/choroid in the context of AMD. This contribution will be significant because it is likely to set the stage for identifying new or combinatorial therapeutic strategies for AMD that could address subretinal fibrosis and inflammation, or otherwise enable AMD progression to be slowed, stalled, or reversed.

NIH Research Projects · FY 2025 · 2024-09

PROJECT SUMMARY (See instructions): Preterm birth affects 1 in 10 infants born in the United States, resulting in significant morbidity and economic cost. Children who are born very preterm (VPT; gestational age<32 weeks) have increased risk for impaired neurodevelopment. VPT infants experience increased physiologic stress while their caregivers experience increased psychological distress-both are associated with impaired neurodevelopment. Epigenetic modifications are proposed as a possible mechanism linking physiologic stress and neurodevelopment in VPT infants. The main objective of the proposed research is to identify the mechanisms by which neonatal physiologic stress induces epigenetic modifications that contribute to impaired neurodevelopment, as well as how caregiver distress moderates the relationship between longitudinal neonatal physiologic stress and neurodevelopmental outcomes. Specifically, the proposed research aims to (1) create and validate novel indices of neonatal physiologic stress in VPT infants; (2) identify the effects of neonatal physiologic stress on epigenetic modifications and later neurodevelopment in VPT infants; and (3) determine the effects of caregiver distress on neurodevelopment in VPT infants. This aligns with the NICHD Strategic Plan 2020 scientific priority-to reduce the incidence of neurodevelopmental disorders by improving the understanding of their origins in the developmental process and identifying potential targets and optimal timing for intervention. During the K99 phase, the Pl's molecular genetic expertise was further developed by adding training in epigenetic analyses via intensive workshops and laboratory experiences, and the Pl's quantitative expertise was expanded to include complex longitudinal analyses. Additionally, the Pl has gained exposure and knowledge of neonatal physiology via the neonatal hemodynamics program at the University of Iowa, led by Drs. McNamara and Rios. Finally, the Pl has developed professional development skills that will be critical for success as a tenure track assistant professor and independent clinical scientist. The academic environment at the University of Iowa is well-suited for the proposed research. Faculty members with expertise in advanced quantitative methods, epigenetics, and neonatal physiology are willing to continue to provide expert mentorship to the Pl as a junior faculty member. The Division of Neonatology conducts numerous research studies on preterm birth each year and has the infrastructure, including an outstanding team of clinical research nurses and a high-risk infant follow-up clinic, to support the proposed research. The Iowa Institute of Human Genetics provides researchers with a state-of-the-art, high-throughput genetic analysis facility and supports research focused on human genetics Numerous institutional organizations provide a variety of opportunities to develop the skills necessary for success as an independent clinical scientist.

NIH Research Projects · FY 2024 · 2024-09

Project Summary Over 60% of cancer patients undergo radiation therapy during their disease process, which frequently leads to injury to surrounding healthy tissue and results in complications such as oral mucositis and proctitis. This normal tissue injury can cause severe morbidity and treatment discontinuation, resulting in potentially inferior tumor control. Attempts to reduce these side effects include systemic radioprotectants, tissue spacing technolo- gies, and radiation techniques, yet these methods are fraught with limitations like selectivity, severe hypotension, issues with spacer placement, and infection. As a result, there is a pressing need for innovative methods for effective radiation protection. To address this need, we propose to develop clinically deliverable RNA strategies for radiation protection, which facilitates the cell-specific targeted delivery of nucleic acids, enables sustained expression of extremophilic proteins for enhanced radioprotective capabilities, and ensures the therapy can be effectively and safely admin- istered into tissues. Our work aims to lay the groundwork for the use of nucleic acid-based therapies for radiation protection. By leveraging the protective qualities of extremophile proteins and developing new delivery methods, we aspire to reduce the impact of radiation-induced injuries, thereby enhancing patient outcomes and quality of life.

NIH Research Projects · FY 2025 · 2024-09

Abstract Overview: This research study will leverage established datasets from nationwide longitudinal lung studies to characterize multi-volume mechanical changes affecting airway and chest wall pathophysiology in chronic obstructive pulmonary disease (COPD) in the presence of emphysema, small airway disease, low bone density, and sarcopenia. Emphysema, air trapping, airway counts and geometry, and multi-volume determined metrics of functional small airway disease (fSAD) have been well investigated. However, changes in airway and chest wall deformation between two lung volumes in COPD and their interactions in the presence of different comorbidities have not been explored. This study will characterize unique subtypes of COPD-related abnormalities in airway and chest wall deformation between inspiratory and expiratory lung volumes, identify their associations in COPD and comorbidities, and assess their impacts on disease progression and clinical outcomes. Methods: Inspiratory and expiratory chest CT scans will be used to define metrics of transverse (Δair-T) and longitudinal (Δair-L) airway deformation and caudocranial (Δwall-CC) and mediolateral (Δwall-ML) chest wall deformation between two lung volumes. Data of healthy never-smokers in the Multi-Ethnic Study of Atherosclerosis Lung (MESALung) will be used to build normative models of different deformation metrics. Genetic Epidemiology of COPD (COPDGene) study data will be used to characterize different subtypes of abnormalities in multi- volume airway and chest wall deformation in COPD. This project will achieve three aims. Aim 1 develops normative models of airway and chest wall deformation metrics, computes participant- and metric-specific standardized scores of deviations from expected values and identifies unique subtypes of lung volume associated airway and chest wall deformation in COPD. Aim 2 characterizes the associations of airway and chest wall subtypes in COPD with demographics, disease severity, radiographic markers, physical activity, smoking status and history, low bone density, and sarcopenia. Aim 3 investigates the associations of 5-year lung function change and clinical outcome metrics with different airway and chest wall subtypes. Novelty: (i) Characterization of novel subtypes of abnormalities in multi-volume airway and chest wall deformation in COPD and assessment of their clinical relevance. (ii) Automation of multi-volume CT-based airway and chest wall deformation metrics. (iii) Normative models of airway and chest wall deformation metrics. Strengths: Established longitudinal data repositories, multi-disciplinary expertise of the research team, and strong preliminary data. Deliverables and Significance: (i) CT-based characterization of new airway and chest wall deformation subtypes will facilitate understanding mechanical changes affecting airway and chest wall pathophysiology and their associations with COPD comorbidities and assessment of their impacts on disease progression and clinical outcomes. (ii) Automation of CT- based metrics of multi-volume airway and chest wall deformation will enable translation of the study findings to large research and clinical collections of chest CT scans. (iii) Normative models will offer references to characterize mechanical changes affecting airway and chest wall pathophysiology in various thoracic diseases.

NSF Awards · FY 2024 · 2024-09

An award is made to the University of Iowa to acquire a Nikon CSU W1 SoRa super-resolution spinning disc confocal microscope (SoRa), to enable long term and high-resolution live imaging to answer critical biological questions. The SoRa will be housed in the department of Biology Carver Center for Imaging (CCI). A diverse group of ~100 graduate and undergraduate student researchers will be potential users. Among these will be students from traditionally underrepresented minorities in science, participating in programs led by faculty in our department. The SoRa will provide valuable practical experience for these young scientists and allow them to perform experiments previously not possible. The SoRa will also be incorporated into the curriculum of advanced teaching labs that train over 160 students each year. In one of these labs, students will acquire industry-related skills by collaborating with a non-profit antibody distributing bank, contributing to building a contemporary workforce. The SoRa will be the focus of an annual virtual tour for ~30 undergraduate students from small colleges, broadening the impact outside the University of Iowa. As SoRa is not available anywhere else in the region, it will enhance collaborative partnerships across eastern Iowa. As part of the CCI, SoRa will serve all research users, including nine major and five minor faculty user groups. The topics these groups study are representative of the wide array of biological questions supported by NSF from the fields of evolution, development, cell biology, neurobiology, and genetics, and use diverse model organisms (yeasts, nematodes, flies, snails and mice). The SoRa will provide answers to important biological questions at the forefront of basic life sciences exploration. Thus, the SoRa will be transformative to user groups performing basic biology research at the University of Iowa, yielding 3D super-resolution live imaging data that was not accessible to labs previously. 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 · 2024-09

PROJECT SUMMARY ABSTRACT Age-related hearing loss (ARHL) results from the cumulative effects of aging on the auditory system. There is growing evidence linking ARHL with cognitive impairment and increased risk of Alzheimer’s disease and related dementias. In fact, the 2017 Lancet Commission for Dementia Prevention, Intervention and Care found that hearing loss is associated with the highest relative risk of dementia (RR 1.9) among 9 potentially modifiable risk factors. It is hypothesized that poor peripheral encoding of sound due to ARHL contributes to cognitive impairment by increasing cortical resources to auditory decoding from memory and other cognitive domains. Research shows an association between the severity of hearing loss and disability in activities of daily living, including shopping, preparing meals and household chores. Older adults with ARHL become socially isolated as communication problems increase, resulting in emotional and cognitive difficulties. The goal of this study is to understand the effect of cochlear implants and hearing aids using real-world data documenting daily performance in study subjects’ natural environments as a predictor of cognitive impairment, or progression from mild cognitive impairment to dementia in people with ARHL. Six groups of individuals, 65+ years of age, will be studied: 1) cochlear implant (Implant) users with normal cognition; 2) Implant candidates who naturalistically retained hearing aids (HA retainers) with normal cognition; 3) Implant users with mild cognitive impairment (MCI); 4) HA retainers with MCI; 5) normal hearing/normal cognition; and 6) normal hearing with MCI. Data from a smartphone ecological momentary assessment (EMA) system is this study’s primary outcome measure, including patient-reported outcomes collected in real-time across multiple domains: 1) listening environment; 2) hearing-related function; 3) hearing loss-related mental health; and 4) cognitive function. Aim 1. Compare the cross-sectional association of Implants or HAs on real-world EMA outcomes in ARHL with normal cognition. Hypothesis: Implants will be associated with better EMA outcomes (auditory function, cognitive performance, social interaction, psychosocial wellbeing) as compared to HA retainers. Aim 2. Compare the longitudinal effects of the use of Implants or HAs in AHRL with and without cognitive impairment on cognitive function, using real-world EMA outcomes and a neuropsychological battery. Hypothesis: Implants will be associated with better cognitive performance and less cognitive decline than HA retainers as measured by both EMA cognitive items and by neuropsychological testing in those with baseline ARHL-related MCI. Aim 3. Deploy study data in our visual analytics platform for precision medicine, clinical decision-support, and data-sharing of hearing/cognitive outcomes by 1) identifying predictor variables, 2) developing individualized predictive models for Implants/HAs, and 3) enabling large scale data-sharing of these models for all clinical and research stakeholders.

NSF Awards · FY 2024 · 2024-09

With support from the Chemical Structure and Dynamics (CSD) program in the Division of Chemistry, Professor Claudio Margulis of the University of Iowa and Professor Andrew Nieuwkoop of Rutgers University are investigating the structure and dynamics of ionic liquids (ILs) and more specifically what they call their “liquid inside a liquid” behavior using a variety of experimental and computational techniques. A challenging aspect of the work is that it deals with an “in-between” dynamical regime in which ILs are too viscous for sophisticated liquid-state NMR techniques but too soft for solid state NMR; this challenge extends also to the computational realm as highly viscous ILs, such as those close to their glass transition, are difficult to simulate. The PIs will use a combination of advanced NMR techniques, scattering, and computer simulations, to jointly investigate intra- and inter-ionic dynamics in an atom-selective manner for a set of selected ILs. Collaboration with Prof. Sharon Lall-Ramnarine from Queensborough Community College and her students as well as other scientists will continue to broaden the reach of the work. Professors Margulis and Nieuwkoop will probe whether the charge network present in all ILs and the apolar domain present for some ILs, each slow down at a different rate; in other words, if the charge network (the matrix) “rigidifies” first and only at lower temperature do the secondary motions of the apolar domain slow down. The study of specific ILs across a range of temperatures could also shed light on structural population changes in the condensed phase. Their discoveries could impact our understanding of fundamental phenomena such as how ions move on time scales relevant to transport phenomena; they could also shed light on recently discovered, but not yet understood, liquid-liquid phase transitions in ILs. Finally, Professors Margulis and Nieuwkoop will continue to engage students from community college, graduate students, and postdocs as well as colleagues at symposia and conferences where vibrant scientific exchanges on ILs will take place. 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 2024 · 2024-09

Autonomous vehicles offer profound societal benefits, promising increased productivity and enhanced quality of life by reducing traffic congestion and improving transportation accessibility. Ensuring the safety of autonomous vehicles is paramount, given their operation on public roads and interaction with human beings. The project aims to develop MELIOREM, an automated tool designed to enhance the safety of autonomous vehicles. By utilizing our nation's high-performance computing infrastructure, MELIOREM will conduct rigorous testing to identify and address potential safety issues before they impact public roads. This initiative ensures that autonomous vehicles are dependable and safe for all road users. Using advanced search techniques, MELIOREM will simulate various driving scenarios to assess how well these vehicles perform under different conditions, leveraging extensive computational power for complex calculations and analysis. By bolstering the safety of self-driving technology, this project not only advances transportation safety but also provides a valuable resource to academia and industry, contributing to the broader professional community. It also creates educational opportunities by training students from diverse backgrounds in higher education. Autonomous vehicles (AVs) promise vast societal benefits of increasing productivity and improving quality of life, from reducing traffic congestion to improving access to transportation. Ensuring AV safety is critical to success in the marketplace, and an essential aspect of AV development to ensure safety is testing. Existing techniques incorporate computerized simulation-based iterations, where the AV under evaluation is stress tested by perturbing traffic parameters and AV internal states to generate safety cases for analysis, identify AV vulnerabilities, and mitigate safety hazards. This process largely involves using high-performance computing (HPC) infrastructure given the enormous amount of computation resources demanded by the simulations. However, current approaches often face state space explosions due to the large search spaces in both internal program executions and external environment parameters when searching for safety cases, making existing tools far from being comprehensive and efficient in HPC. Furthermore, due to the complicated structure of AV software stack, error resilience is not yet well understood, making diagnosis and protection extremely time consuming. This project will develop an efficient and comprehensive testing infrastructure, MELIOREM, for characterizing, assessing, and identifying vulnerabilities in AV software systems in evolving traffic situations. The core purpose of this work is practicality, enabling domain scientists to generate safety cases for characterizing and understanding AV safety, and AV developers to identify AV safety vulnerabilities using existing HPC infrastructure. This project will develop a series of algorithms to optimize test coverage, emulation efficiencies, and identify representative safety cases for an AV under test. This work will resolve these AV development issues with respect to their practical analysis by applying MELIOREM in intelligent cyber-systems in transportation and crash analysis research domains. This project is jointly funded by the OAC Cyberinfrastructure for Sustained Scientific Innovation (CSSI) program and the Division of Information and Intelligent Systems (IIS). 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 2024 · 2024-09

The broader impact of this I-Corps project is based on the development of an innovative and cost-effective mechanical ventilator designed to address critical respiratory needs in low-resource settings. Acute respiratory distress affects about 3 million people annually, with mortality rates reaching 90% in under-resourced areas. This technology aims to save lives, benefiting patients with lung infections and those undergoing some invasive surgeries. With a 71% survival rate among ventilated patients, this solution could substantially elevate survival rates. Additionally, the cost-effectiveness of this solution could provide financial relief to healthcare systems, enabling reallocation of funds to other pressing health issues and fostering a more efficient healthcare system. This project contributes to global health equity, enhancing the quality of care in underserved communities through high-quality, low-cost, practical engineering solutions. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. The solution is based on the development of an innovative and cost-effective mechanical ventilator designed for low-resource communities. The technology focuses on a streamlined mechanical ventilation system that provides continuous respiratory support for patients with acute respiratory distress. The device's reliability, durability, and ease of use, even by non-specialized healthcare workers, are essential functionalities. By excluding unnecessary high-end components, the device remains effective while significantly reducing costs. Technical results from extensive prototype testing demonstrated the ventilator’s ability to deliver consistent and adjustable ventilation to both neonates and adults. Performance evaluations in simulated environments confirmed its efficiency and reliability, showcasing its potential to maintain critical respiratory functions without continuous manual operation. The merit of this project lies in bridging the health resource gap with practical engineering solutions tailored to low-resource constraints. 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 2024 · 2024-09

PROJECT SUMMARY/ABSTRACT The University of Iowa Flow Cytometry Facility was established in 1979 and currently serves 128 principal investigators spanning 31 departments across four colleges. This group continuously receives NIH support for their work on diverse biomedical research projects that advance our understanding of biological processes that are essential for human health and identify novel methods to detect and treat a wide variety of diseases. Recent advances in flow cytometry, microscopy, and single-cell sequencing have increasingly enabled researchers to identify specific cell populations. Consequently, our investigators require cutting-edge instrumentation that can accommodate a wide range of experimental conditions to address new research questions that arise due to these expanding technologies. Currently, our Facility operates six heavily used benchtop flow cytometers. However, the Facility lacks an imaging cytometer, which harnesses the high throughput, statistically robust data acquisition of a flow cytometer with the imaging and morphological capabilities of microscopy. In the absence of this, investigators must run samples on a flow cytometer to generate quantitative data and use the rest of their sample, or a duplicate of their sample, to generate qualitative images on a microscope. This workflow is incompatible with rare cell populations, limits the rigor and reproducibility of experiments due to different labeling schemes, and is costly and time consuming. The nearest publicly accessible imaging cytometer is over 200 miles away. This lack of accessibility to an imaging cytometer has a significant adverse impact on the ability of our investigators to obtain detailed images and corresponding robust statistical data to assess a wide range of biological questions. Thus, there is an urgent need to acquire an imaging cytometer in the Flow Cytometry Facility at the University of Iowa so investigators can expand their capacity to understand cell morphology, identify subcellular localization, assess protein- protein interactions, and distinguish specific cell staining from background in rare cell populations in a quantitative manner, which will enable them to advance their research in new directions. This proposal requests funds for a Cytek Amnis ImageStreamX MkII imaging cytometer to provide NIH-funded investigators and other researchers at the University of Iowa with access to an instrument that can generate both qualitative and quantitative data, thus reducing the time needed for data acquisition, sample degradation, and sample-to-sample variation in the case where different samples are run using flow cytometry vs microscopy. This will allow for continued support and enhancement of research projects carried out at the University of Iowa and in the state of Iowa, many of which are part of clinical trials or crucial pre-clinical or basic science studies, and will ensure the Facility continues to meet its overall goal of providing state-of-the-art instrumentation that supports biomedical research to improve our understanding of human health and disease.

NSF Awards · FY 2024 · 2024-09

Time is a fundamental resource in organizations, shaping how work is performed and influencing the overall efficiency and productivity of the organization. However, effective time management remains a significant challenge, particularly in contemporary workplaces featuring rapidity and flexibility. Ineffective time management in organizations is problematic, as it not only hinders project completion and impedes productivity but also leads to poor workload management and increases employee stress and burnout. This project investigates how leaders and followers can collaborate to initiate and coordinate their time management efforts within organizations. The research aims to enhance workplace practices related to time management and develop a workforce skilled in managing time effectively. By doing so, this project seeks to foster a more productive work environment and improve the overall well-being of the workforce. In this project, the research team focuses on the concept of temporal management, defined as the strategic use of time by individuals to affect work patterns, schedules, and productivity within an organization. Through three mixed-methods projects, this research aims to contribute significantly to understanding how leaders and followers collaboratively optimize time in organizational settings. The first project (Project 1) elucidates the conceptual nature and dimensionality of temporal management in leader-follower dyads. The second project (Project 2) advances and tests a formal theory of the dynamic occurrence and influence of leader and follower temporal management. The third project (Project 3) investigates the dyad-centric patterns of leader and follower temporal management and their impacts in the context of contemporary workplaces. 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 2024 · 2024-09

With the support of the Chemical Catalysis Program in the Division of Chemistry, Professor Christopher Pigge of the University of Iowa is developing new transition metal catalysts (catalysts are chemical additives that help a reaction occur or proceed more rapidly) for use in organic synthesis. Broadly applicable and highly active catalysts are essential tools in chemistry for the efficient construction of small molecules, including molecules that are used in pharmaceuticals, materials and polymers, and a host of other applications. The reactivity and scope of metal catalysts is often influenced by supporting ligands; this project is developing enhanced and tunable catalysts by incorporating novel and readily available ligands into catalytically relevant metal complexes. In addition to the wide-ranging impact of the new catalysts, the broader impacts of this work are allowing students at the undergraduate and graduate level to be involved in state-of-the-art training in organic and organometallic chemistry, Over the course of this training, the students are developing expertise in catalyst design and evaluation. Outreach efforts to middle and high school students are further broadening participation in STEM-related activities. Carbon-donor (C-donor) ligands show promise as key components of highly active yet stable transition metal catalysts, but the chemistry of C-donor metal complexes is underdeveloped. This project is investigating the catalytic activity of metal complexes that feature novel C-donor ligands prepared from N-alkylpyridinium salts. These molecular frameworks are readily accessible and are easily modified to accommodate monodentate and polydentate ligand scaffolds, including chiral non-racemic ligands for use in asymmetric catalysis. The electron-donating properties of the ligands are systematically tuned through the incorporation of different activating groups along the pyridine periphery, allowing access to ylide-type, yldiide-type, and carbone-type C-donor groups from a common molecular core. Organometallic complexes prepared from catalytically active metal centers (such as Pd, Rh, and Au) are easily obtained and are being developed for use in important synthetic transformations that engage an array of common organic functional groups. 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 2024 · 2024-08

Project Summary/Abstract This is a request to upgrade our current Siemens SOMATOM Force research energy integrating CT scanner to a newly released photon-counting CT scanner (Siemens NAEOTOM Alpha). While we have made great progress in the use of quantitative CT imaging to sub-phenotype lung disease there are limitations which this new scanner design will eliminate. Beam hardening is a scanning artifact which makes the lung appear less dense than it actually is. Because the new scanner directly counts every photon passing through the body and bins them into energy ranges, by reconstructing the lungs with a narrower photon range (selected for the kV range which best maximizes tissue contrast) will essentiall eliminate this error. Additionally, because the detection of photons is a digital process, the noise associated with analogue to digital conversion of light signals is eliminated, significantly reducing electronic noise. The spatial resolution is considerably higher and there is a choice of keeping similar dose as previous protocols (which have already been reduced nearly 10 fold) while taking advantage of the improved spatial resolution, or significanlty reducing the dose further and keep the same resolution. Because the photons are captured along with their energy characteristics, the photon count at each location can be binned into energy ranges, allowing for the seperation of multiple materials such as krypton and gadolinium for the simultaneous assessment of ventilation and perfusion. Additional contrast agents are under development to also, simultaneously, tag inflammation. Because of the improved contrast resolution, we will be able to further reduce the amount of contrast agent used by as much as 40%. We propose 9 major projects, all associated with either multi-center studies seeking new phenotypes of lung disease (COPD, Asthma, IPF, PASC (long COVID) etc. , or local investigations into lung pathologies. The scanner promises to improve the ability to assess airway wall thickness further into the lung periphery and to make possible the identification and seperation of arteries and veins.with similar abilities to extend to the lung periphery. Through deep learning and transfer learning, we propose that these improvement will help advance utility of existing scanner images as well. Because we are the radiology Center, the scanner not only allows us to take advantage of the advanced methodology locally, but we will be able to continue to disseminate newer protocols, keeping the lung community at imaging state-of-the-art. There are already 7 such scanners delivered to cinical centers within the US and this is expected to rapidly expand. Thus, the opportunity for research translation.

NIH Research Projects · FY 2025 · 2024-08

SUMMARY An estimated 30-70% of obstructive sleep apnea (OSA) patients are intolerant to first-line continuous positive airway pressure (CPAP) therapy for a variety of reasons. A variety of alternatives to CPAP exist, including the 2014 FDA approved hypoglossal nerve stimulation (HNS) therapy. The current clinical practice to screen OSA patients for HNS surgery is to perform a drug induced sleep endoscopy (DISE) procedure to assess airway collapse. However, DISE is challenged by several limitations including potential alteration of natural airway collapse due to the inserted endoscope, the lack of imaging surrounding soft-tissue, the lack of simultaneously imaging the full 3D extent of the upper airway, and the purely qualitative interpretation of airway collapse. Despite these challenges, it is mainly used because there is no better alternative. In this proposal, we propose to address this gap by systematically developing a novel 3D dynamic MRI (3D-DMRI) scheme capable of quantitating airway collapse during sleep. We propose a novel scheme that synergistically combine (a) parallel imaging via dedicated airway coils, (b) motion robust 3D stack of spiral encoding, (c) learning based spatio- temporal regularization, and (e) quantitative analysis to extract imaging phenotypes to characterize 3D airway collapse. In Aim 1, we will develop the scheme and systematically validate it on a cohort of OSA patients being screened for HNS therapy. In Aim 2, we will develop a deep transfer learning based segmentation scheme to extract 3D-DMRI based phenotypes that characterize spatio-temporal patterns of airway collapse. In Aim 3, we will assess the clinical utility of our scheme to characterize the pattern of airway shaping and collapse both in the awake and sleep state, and will evaluate it against existing DISE clinical protocol. In aim 4, we will determine if the 3D-DMRI derived imaging-based biomarkers are predictive of clinical outcomes of HNS therapy. This study will leverage the principal investigator’s expertise in rapid upper-airway MRI, along with collaborators’ interdisciplinary expertise in otorhinolaryngology, clinical sleep medicine, image analysis. Successful completion of this study will showcase the feasibility of MRI-based “virtual endoscopy” and immediately lead to several clinical trials for OSA. Specifically, we anticipate having demonstrated 3D-DMRI to be an effective alternative to DISE for determining the eligibility of patients with OSA for HNS, and show preliminary evidence if these biomarkers are predictive for HNS treatment success.

NSF Awards · FY 2024 · 2024-08

Understanding how aquatic plant canopies interact with flowing water is crucial for many aspects of environmental science, including river habitat restoration, flood management, and sustainable energy solutions. This project focuses on studying the forces that influence the movement and stability of these underwater and emergent canopies. By examining flexible and rigid plant structures in river environments, the researchers aim to uncover the complex interactions between water flow and plant life. The findings will enhance our ability to predict and manage water flow in natural and engineered environments, leading to more effective conservation strategies and improved designs for renewable energy systems. The project also promotes community engagement and education, with efforts to involve students from under-represented communities in STEM through university programs and public outreach activities, including interactive exhibits and public lectures. The research involves a combination of experiments and numerical simulations to investigate how different types of plant canopies affect water flow and drag forces. Experiments will measure the overall resistance of plant canopies and analyze the flow patterns around them. Advanced flow and object-tracking techniques will be used to capture detailed data on canopy movements and water currents. Numerical simulations will complement these experiments by better understanding local drag forces and drag distribution within canopies. Artificial neural networks will be developed to predict the drag of canopies in various configurations. This project will generate comprehensive datasets to train machine learning models, ultimately leading to a generalized formulation for predicting canopy drag in different environments. The results will be shared through publications, presentations, and a publicly accessible digital repository, contributing to the broader scientific knowledge and practical applications in the field. 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 2024 · 2024-08

WIth support from the Chemical Structure, Dynamics, and Mechanisms-A (CSDM-A) program of the Chemistry Division and the Established Program to Stimulate Competitive Research (EPSCoR), Pere Miró and his research group at the University of South Dakota are using advanced computational approaches to understand the nucleation and growth of functionalized polyoxovanadate-alkoxide clusters, as well as the ability of these clusters to catalyze the reactions of small molecules. The development of molecular catalysts that have the ability to accelerate complex chemical reactions involving many electrons remains a major challenge due to changes that often affect the durability and behavior of such species under harsh reaction conditions. Therefore, understanding and controlling the properties of these catalytic compounds is of fundamental importance, and relies on the ability to manipulate the evolution of transient species in solution. The polyoxovanadate-alkoxide clusters under study here will provide a useful platform better understand fundamental aspects of the synthesis, reactivity, and durability of metal oxide catalysts, in general, as well as the catalytic activation of small molecules. This work will contribute to the long-term goal of the Miró research group to use modern computational methodologies to discover new roadmaps for the nucleation of molecular mimics of catalytic metal-oxide materials. The project includes an educational outreach program involving hands-on workshops at neighboring tribal colleges, the engagement of tribal undergraduate students in science, technology, engineering, and mathematics (STEM) research, and leading National Chemistry Week activities for students at K-12 schools. Pere Miró and his research team will use high-level quantum chemical calculations and neural network algorithms to examine the nucleation mechanism of first-row functionalized polyoxovanadate-alkoxide clusters--up to the formation of hexameric species--as well as to better understand the impact of dynamic experimental conditions on the structure-redox relationships and multi-electron reactivity of the clusters. Specifically, a combination of density functional theory calculations benchmarked against domain-based local pair natural orbital coupled cluster and second-order complete active space methodologies are being used to characterize nucleation intermediates and derive neural network potentials to streamline the exploration of the nucleation space. This research seeks to enrich the understanding of structure-function relationships that control nucleation and electrocatalytic properties. The scientific broader impacts of this work include transforming the way the organometallic chemistry community views function-oriented synthesis of these species using computational methodologies and to guide the discovery of new functionalities. The project also will provide advanced training opportunities for graduate and undergraduate students, including directed training opportunities for students from groups that are underrepresented in the physical sciences. 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 2024 · 2024-08

The National Science Foundation (NSF) Graduate Research Fellowship Program (GRFP) is a highly competitive, federal fellowship program. GRFP helps ensure the vitality and diversity of the scientific and engineering workforce of the United States. The program recognizes and supports outstanding graduate students who are pursuing research-based master's and doctoral degrees in science, technology, engineering, and mathematics (STEM) and in STEM education. The GRFP provides three years of financial support for the graduate education of individuals who have demonstrated their potential for significant research achievements in STEM and STEM education. This award supports the NSF Graduate Fellows pursuing graduate education at this GRFP 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 · 2024-08

Although there has been considerable interest in using remote monitoring in diseases like Parkinson’s disease, Alzheimer’s disease, and other Alzheimer’s disease-related dementias, there has been essentially no change in clinical care. Yet, remote monitoring could radically reduce barriers to care, especially in rural areas – 80% of rural areas medically underserved. The long-term goal is to use remote monitoring to improve the lives of people with neurodegenerative causes of dementia. The overall objectives of this application are to identify the value of wearable devices, automated fine-motor and speech assessments in detecting and measuring cognitive and non-cognitive symptoms of Parkinson’s disease. The central hypothesis is that low-cost wearable devices combined with computer vision and speech analysis can provide useful, holistic assessment of Parkinson’s disease. The rationale for this project is that remote monitoring can increase the effectiveness of expert care, alleviating barriers of access and distance in underserved, rural communities. The hypothesis will be tested with two specific aims: 1) Identify the value of low-cost, holistic assessment for predicting Parkinson’s disease diagnosis and cognitive impairment and 2) Identify the value of low-cost, holistic assessment for predicting one-year cognitive, motor progression in Parkinson’s disease. In the first aim, people with possible Parkinson’s disease will be provided an activity tracker and conduct home-based motor and speech assessments with the goal of building a classifier to predict the ultimate diagnosis (Parkinson’s disease versus not Parkinson’s disease) and cognitive status at baseline (normal cognitive, mild cognitive impairment, dementia). The second aim will build a cohort of people recently diagnosed with Parkinson’s disease and conduct a 4-week assessment using an activity tracking watch and home-based motor and speech assessments. The objective will be to improve prediction of cognitive and motor symptoms at 1 year. The proposed research is innovative because it focuses on using data collection using low-cost, commercially available devices to construct a holistic measure of both the motor and cognitive manifestations of Parkinson’s disease. The proposed research is significant because it is expected to provide a low-cost framework useful for non-expert providers to screen for and evaluate Parkinson’s disease and to provide a more accurate prognosis for people newly diagnosed. As a career development grant, this proposal is ideal: it builds on the applicant’s past skills in health economics by adding knowledge of neuroscience, neurodegenerative diseases and dementia, human subjects, and clinical research – all relatively novel areas for the applicant. The applicant will accomplish these career development goals through both conducting the proposed research and didactic instruction in clinical trials, neuroscience, and neuropathology. The applicant’s division and institution are dedicated to providing the needed support and resources for success and both have outstanding track records for transforming ESIs into successful, independent, NIH-funded researchers.

NIH Research Projects · FY 2025 · 2024-08

Project Abstract Maternal viral infections during pregnancy may result in catastrophic outcomes for her health as well as for her developing fetus. Recent emerging virus epidemics and pandemics such as those with Ebola Virus (EBOV), Zika Virus (ZIKV) and SARS-CoV-2 have highlighted the impact of viral infection on pregnancy outcomes. Yet a dearth of data exists pertaining to viral infection and pathogenesis in the placenta and the role of the placenta in viral transmission to the fetus. In pregnancy, EBOV infection of pregnant mother results in ~100% fatality for her fetus or neonate with ~60% maternal mortality. Placental immunostaining from EVD outbreaks in Africa demonstrate viral antigen in placental tissues as well as viral RNA in neonates or fetuses of infected mothers. This suggests vertical transmission of virus from mother to fetus. However, rigorous experimental evaluation of maternal transmission and placental infection has not been performed. The tropism of EBOV for placental cells, mechanisms of cellular entry and route of infection from mother to fetus are currently unknown. The long- term goal of this proposal is to understand the biology of EBOV in pregnancy through understanding a) the tropism of EBOV within placental tissues that may lead to the transplacental transmission of virus from mom to baby as well as b) cell surface receptors utilized by EBOV within placental tissues. Aim1 will seek to define the tropism of EBOV in the placenta in early and late pregnancy. For these tropism studies, we will use a model virus, recombinant vesicular stomatitis virus expressing EBOV glycoprotein (rVSV/EBOV GP), to examine viral tropism in placental and fetal tissues. Using this model, we will explore the role of maternal and placental macrophages as well as placental trophoblasts driving tropism. In Aim 2, we will investigate the role of phosphatidylserine (PS) receptors in the placental infection and transmission of virus from placenta to the fetus. In Aim 3, collaborative efforts by Dr. Andrea Marzi at Rocky Mountain Laboratories will utilize mouse- adapted EBOV (maEBOV) in WT C57BL/6 mouse timed-pregnancies to evaluate virus load and tropism at later gestational times. Further, maEBOV-infected placental and fetal tissues will be evaluated for targeted innate immune responses. The data garnered from these targeted and rigorous experiments will establish the first pregnancy model of EBOV, allowing us to mechanistically explore EBOV tropism required for the virus to traffic from dams to fetuses. These studies will provide fundamental information on EBOV biology that will aid in the discovery or development of therapeutic interventions for EBOV infection during pregnancy.

NIH Research Projects · FY 2025 · 2024-08

PROJECT SUMMARY Duchenne Muscular Dystrophy (DMD) is the most common muscular dystrophy seen in children, which affects both muscle and bone. To date, the mechanisms that contribute to the poor skeletal health in DMD are not fully understood and no targeted therapies exist to slow or halt the progression of osteoporosis and related fractures. We have identified a novel bone-regulating myokine, FGF-21, which is typically not expressed in skeletal muscle under physiological conditions, is dramatically increased in dystrophic skeletal muscles in DMD mouse models. However, the mechanisms which drive FGF21 expression in dystrophic muscle and the pathological role of FGF21 on bone metabolism in DMD are not clear, representing a significant gap in knowledge. The purpose of this proposal is to identify the cellular source of elevated FGF21, determine the molecular mechanism(s) that drive FGF21 expression, and to characterize the pathological effects of muscle-derived FGF21 on bone in DMD. The cellular and molecular mechanisms of upregulated FGF21 expression will be determined in skeletal muscle of dystrophic mouse models. The pathological role of muscle-derived FGF21 on skeletal muscle, bone and whole-body metabolism will be determined by skeletal muscle conditional FGF21 knock out animals and in in vitro cell models. Completion of these studies will not only provide understanding of the pathogenesis of DMD skeletal abnormalities but also elucidate a novel muscle/bone crosstalk signaling pathway mediated via myokine FGF21. The proposed studies will provide the groundwork for developing potential therapies targeting FGF21 signaling to manage poor bone health in DMD patients.

NIH Research Projects · FY 2025 · 2024-08

ABSTRACT The oral cavity is a complex environment where a diverse array of organisms coexists in dynamic interplay with the human immune system. While bacteria, archaea, and fungi have traditionally been the focus of research on the human microbiome, recent studies have highlighted the significant role of viruses in shaping the oral microenvironment. These submicroscopic agents, collectively known as the virome, include eukaryotic viruses, prokaryotic (phages) viruses, and co-infective (virophages) viruses are crucial to maintaining health and may play a role in the development and persistence of diseases. In ocean and soil communities, viruses have been found to influence biogeochemical processes and control microbial populations through infection and lysis. Similarly, in the human oral cavity, viruses may have a substantial impact on oral health. Although research efforts focused on the oral virome are relatively new, recent technological advancements have made it possible to explore this area more comprehensively. High-Throughput Sequencing and sophisticated viral discovery tools have enabled researchers to delve deeper into the significance of viral communities. While there have been a few recent studies of the virome in the oral cavity providing preliminary evidence of its importance, there exists a large untapped resource in the form of hundreds of published metagenomic and metatranscriptomic studies of the oral cavity in varying states of health and disease that have only been used to study the traditional microbiome. Here we propose to mine this resource using innovative algorithmic approaches and multi-omic analysis tools to pursue a comprehensive examination of the oral virome and its interactions with the microbiome. By shedding light on the role of viruses in maintaining oral health and contributing to disease, this research will illuminate a neglected member of the oral microenvironment and potentially have far-reaching implications in the search for alternatives to antibiotics, such as phage therapies. Understanding the intricate dynamics of the oral microenvironment will inspire new approaches to promote oral health and prevent/manage oral diseases more effectively.

NSF Awards · FY 2024 · 2024-08

The 38th Annual Gibbs Conference on Biothermodynamics will be held at the Touch of Nature Outdoor Education Center in Carbondale, Illinois on September 28-October 1, 2024. The Gibbs Conference brings together researchers with similar interests in understanding how changes in structure and energetics manifest in biological function. This conference provides a unique opportunity for scientific exchange and collegial interactions among researchers, while fostering the professional growth of early career trainees and promoting an equitable, accessible, and inclusive biothermodynamics community. The 2024 conference will bring together scientists from across the country as invited speakers and create numerous opportunities for trainees and early-career scientists to connect with peers and mentors. Biological thermodynamics aims to understand the energetics of chemical processes that lead to biological function. Modern biothermodynamics has evolved new ideas with the use of technological advancements to probe the basic tenets of allostery. More broadly, biothermodynamics now includes structural biology to help link the gap between structure, energetics, and function. To move the field forward, there is a need to bring together various disciplines. The field is now at the intersection of computational methodologies, detailed kinetic investigations, structural biology, molecular biology, high- throughput approaches, and classical thermodynamics. Combining these diverse disciplines will lead to new developments in all areas of biology. Developments in modern biothermodynamics will continue to lead to the development of new approaches and methodologies to study protein-protein and protein-ligand interactions, enzymes, and their cellular pathways. This meeting is supported by the Molecular Biophysics Cluster of the Division of Molecular and Cellular Biosciences. 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.