University Of Arizona

NSF Awards · FY 2024 · 2024-09

This award combines novel detections of gravity waves and particles with traditional astronomy observations to better understand the physics of merging black holes and neutron stars. This way of exploring the universe is powerful but presents challenges. Often the direction and origin of the merger is uncertain, and astronomers must search large areas of the sky to identify any explosions that may be related. Response time is also important, as any astronomical signal may only last for hours and may be confused with many unrelated sources in the night sky. To address this challenge, a team led by the University of Arizona and Northwestern University will develop a tool that uses data archives and real-time observations to help astronomers assess incoming candidate counterparts to gravity wave and neutrino events. This product will lower the barrier to enter this exciting field and bring together communities including high schools, smaller institutions and amateur astronomers. This award will fund scholarships for high school students to conduct related research. The team will build the Treasure TROVE (a Tool for Rapid Object Vetting and Examination), which will use the vast stores of information in astronomical archives and real-time searches for supernovae to help multi-messenger astronomers assess and prioritize incoming candidate counterparts to gravitational wave events and neutrinos. For each candidate transient counterpart to a gravitational wave or particle messenger, the Treasure TROVE will crossmatch it with galaxy catalogs, archival imaging, and other public archives to determine whether the distance, variability, and association with other types of transients is consistent with the messenger. This will allow for ~50% of candidates to be discarded without any further need of follow-up, and for the most promising candidates to be prioritized. This program will involve community engagement, providing workshops, tutorials, and public workspaces that will ensure the broadest possible community can use the Treasure TROVE and participate in multi-messenger astronomy. Multi-messenger event localizations can span 1-1000s square degrees on the sky, and follow-up electromagnetic observations can uncover tens to hundreds of transients within that region - only one of which can be related to the gravitational wave, neutrino, or high-energy particle alert. The Treasure TROVE tool will take basic information of recent transients and automatically place each object in context using historical light curves and host galaxy identification, along with cross-matching with image archives and multiple point source, variable, and quasar catalogs. The Treasure TROVE will simplify this task with an easy-to-use software and web interface, optimizing follow-up telescope resources and speeding discovery. 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

A major goal of modern astronomy is the detection of Earth-like exoplanets. To do this, it is necessary to block the light from the central star so that any planets are not lost in the glare. Blocking out this central bright star is a significant challenge that must be met in order to find and study faint Earth-like planets. This investigation will contribute toward this goal by developing a new type of coronagraph, a special device for blocking the starlight, for mid-infrared instruments. The investigators will demonstrate this new technology through a first-of-its-kind observation of a nearby star that could lead to the discovery of new exoplanets. This program will more broadly impact society through student research and education opportunities. In addition, the investigators will help to develop a diverse, globally competitive STEM workforce by hosting a workshop on the technique of coronagraphy, and promoting the full participation of women, disabled persons, and underrepresented minorities in STEM fields through teaching and inclusive educational programs. This project will result in the manufacture and commissioning of a new type of coronagraph for mid-infrared exoplanet imaging observations: the Quadruple Annular Groove Phase Mask (Q-AGPM). The Q-AGPM builds on the successful design of the classical AGPM. The quadruple-etched design in a single unit will enable the nulling power of the typical AGPM design to be combined with multiple beams and/or multiple beam positions to mitigate the mid-IR background through differential imaging. The investigators anticipate a Q-AGPM equipped 8m telescope to be two and a half times more sensitive–covering an estimated ~60% of the current gap between imaging warm sub-Neptunes and super-Earths around the closest stars. They will demonstrate this gain in sensitivity by conducting a test observation. In a one week campaign (approximately three to six nights, depending on weather), the team will demonstrate the sensitivity of a single-target long exposure, which could lead to the discovery of new exoplanets. This program will more broadly impact the community by creating student research opportunities and by hosting a workshop for advanced undergraduate and graduate students that will focus on the history, modern designs, and important scientific results of coronagraphy. 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 Satiation is an important aspect of interoception that translates gut signals, such as cholecystokinin (CCK), into eating suppression. Insatiable appetite is associated with developmental genetic diseases including Prader-Willi Syndrome (PWS) and Shafer-Young Syndrome (SYS). Paradoxically, individuals with PWS have higher levels of plasma CCK but consume more food, suggesting that the neural mechanism responsible for detecting satiation signals is impaired and cannot convert satiation information into eating suppression. However, how the neural circuit that regulates satiation is impaired in these diseases is still unknown. PWS and SYS share a common mutation in the Magel2 gene, suggesting that the mutation of this gene might impair the satiation circuit. Consistent with this, our preliminary results indicate that CCK fails to suppress food intake in Magel2-null mice. Our previous studies have identified a specific population of neurons in the central nucleus of the amygdala (CeA) marked by the expression of protein kinase C-delta, which plays a critical role in detecting CCK. Silencing these neurons prevents the eating suppression caused by CCK and activation of these neurons suppresses food intake. Here, we found that the response of CeA PKC-δ neurons to CCK is reduced in Magel2 null mice. Therefore, we hypothesize that the neural circuits involving CeA PKC-δ neurons are impaired after Magel2 mutation. In this proposal, we aim to determine how the CeA PKC-δ neurons are affected by the Magel2 mutation, using recently developed in vivo calcium imaging and electrophysiology approaches (Aim 1). Because the total number of CeA PKC-δ neurons is not affected by Magel2-mutation, we will also test the hypothesis that activation of CeA PKC- δ neurons suppresses appetite in Magel2-null mice (Aim 2). Successful completion of the proposed studies will help us understand how satiation and appetite are regulated in the brains of individuals with PWS and SYS. Additionally, it may suggest novel druggable targets in the brain to control insatiable appetite and obesity in these diseases, ultimately improving the quality of life.

NSF Awards · FY 2024 · 2024-09

All chemical elements are present dissolved in the ocean. Differences in their concentrations and in the relative amounts of their isotopes at various locations and depths are used to understand the workings of the ocean and the geochemical cycles of the planet as a whole. In this project, investigators from three institutions will conduct the first study of the marine chemistry of zirconium isotopes. Pilot data from the team have indicated differences in isotopic composition between seawater and sediments. The proposed work will build on these pilot data by characterizing the zirconium isotopic composition of a comprehensive array of seawater, particle, and sediment samples already collected from the Pacific Ocean. One aim of the work will be to test the idea of whether zirconium isotopes in sediments provide a record of past ocean conditions. The project will support one PhD student and provide research experience for one undergraduate student. The results of this research will be incorporated into class material taught by the PIs and reported in plain language summaries on their research websites and through university press releases. This work will support a diverse, interdisciplinary team of three early career faculty. The team will promote broadening participation in science through targeted educational outreach including the development of educational modules for high school students to spur interest in chemical oceanography and isotope geochemistry among students at an early career stage. Previous work on high field strength elements including zirconium (Zr) and hafnium (Hf) indicated that the ratio of dissolved Zr/Hf varies extensively and systematically with latitude and depth in the ocean. Pilot data obtained by this team on the stable Zr isotopic composition of marine authigenic sediments and seawater has revealed systematic fractionations, but further investigation of this proxy in seawater profiles and marine particulates that intersect major currents is crucial for: i) providing insight into the mechanisms responsible for the isotopic fractionations observed in the ocean; and ii) further developing their application as a potential tracer of paleo-oceanographic processes. The proposed work aims to build upon the pilot observations by characterizing the Zr isotopic composition of seawater, marine particulates, sediments, and leaches in an array of well-characterized samples collected during a previous cruise. This project will apply high-precision, novel non-traditional stable isotope techniques to marine samples to: (1) determine the stable Zr isotopic composition of various endmembers in the ocean (dissolved, particulate, authigenic sediments), (2) probe whether these isotopic compositions correlate with water mass age, (3) test whether the Zr isotopic composition of authigenic sediments faithfully record the water composition they originated from, and (4) test whether adsorption of dissolved Zr onto sinking particulates is the driver of the observed Zr isotopic fractionation in the ocean. 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 The goal of this K99/R00 application is to support and facilitate the transition of Dr. Robert Jackson’s mentored postdoctoral research project to an independent research program focused on spatiotemporal modeling of cancer-causing human papillomavirus (HPV) infection in human oral epithelia. HPVs are responsible for 5% of all cancers worldwide. HPV causes genital cancers, but also an increasing number of oral cancers, most often in the tonsils and caused by HPV16. In the United States, the rate of HPV-associated oral cancers has surpassed cervical cancers and is considered an epidemic. HPV16 can transform host oral epithelial cells and lead to oral cancer, most often arising in the tonsillar crypt, but its normal viral lifecycle is reliant on epithelial differentiation to yield a productive infection. To address the oral health burden caused by HPV16, Dr. Jackson proposes three specific aims to assess and characterize HPV16 transforming vs productive infections in oral epithelia. Dr. Jackson’s preliminary work, using three-dimensional oral epithelial culture and single-cell transcriptomics, demonstrates that tonsillar crypt and surface epithelial subtypes have unique differentiation phenotypes and host regulator activity. In the K99 mentored phase, Dr. Jackson will assess HPV16’s lifecycle in tonsil epithelial subtypes and test the hypothesis that a host transcription factor, Peroxisome Proliferator- Activated Receptor Alpha (PPARα), regulates viral productivity and tumorigenesis. In Specific Aim 1, he will quantify HPV16 lifecycle stages and tumourigenicity in tonsillar crypt and surface epithelia. In Specific Aim 2, he will modulate PPARα activity to determine if it controls viral productivity and tumorigenicity. In the R00 independent phase, in Specific Aim 3, Dr. Jackson will establish his independent research program and define the spatiotemporal viral-host transcriptome across oropharyngeal tissues. The proposed mentored research will be performed at the University of Arizona, an ideal research and training environment, and will be coupled with a career development plan including structured professional development and new techniques training. Dr. Jackson will be supported by his primary mentor, Dr. Koenraad Van Doorslaer, as well as an advisory committee that will ensure his successful transition to a tenure-track faculty position for the independent phase. Dr. Jackson’s proposed research aligns with the NIDCR’s strategic priority to integrate oral and general health, with an objective to advance prevention, early detection, and treatments for head and neck cancers using the tactic of characterizing HPV+ oropharyngeal cancers. Dr. Jackson’s research is relevant as it intersects with notices of special interest including single-cell level spatiotemporal mapping of oral tissue and incorporates computational approaches.

NIH Research Projects · FY 2024 · 2024-09

ABSTRACT Despite the widespread availability of low-cost, evidence-based preventative strategies like human milk feeding, feeding guidelines and medication stewardship, necrotizing enterocolitis (NEC) remains a chief cause of emergency surgery and death in premature infants and disproportionately affects Black and Hispanic infants. Under-resourced neonatal intensive care units (NICUs) struggle to support staff education, a culture that engages in quality improvement (QI), or access essential resources like donor human milk and adequate nursing care. The intersectionality of these factors in concert with social determinants of health may contribute to NEC disparities. NICU disparities are lessened with intense quality improvement, although equity-focused quality improvement is rare. In 2016, the U.S. Legislature signed the “Expanding Capacity for Health Outcomes (ECHO) Act” into law to spur “technology-enabled collaborative learning and capacity building models” and accelerate the impact of these models on preventing disease and improving public health outcomes among underserved groups. Our team has effectively implemented a neonatal Project ECHO (NeoECHO) which supports implementation of NEC preventing best practices and our team has shown its benefits to reach NICU clinicians in under-resourced settings. Using a stepped-wedge clinical trial design and engagement of patient- family advocate partners and a national neonatal practice group, we will provide active facilitation via tele- mentoring and working with local internal facilitators in 30 NICUs to examine the effects of a NeoECHO approach to reduce NEC rates and impacts on NEC disparities within and across units. Aims will: 1) Compare the effectiveness of NeoECHO to usual care on NICU-level outcomes for NEC and clinical care. 2) Describe the structural organizational contexts and unit-level differences in quality outcomes at baseline and examine their contribution to intervention effectiveness. 3) Evaluate NeoECHO implementation (including features of engagement, reach, number of recommended practices adopted and embedded in practice, retention of NICUs in the program, effect on clinician confidence, and cost). Using an implementation determinant framework known as the Health Equity Implementation Framework, we will qualitatively explore the barriers and facilitators to implementation of NeoECHO to allow for a more contextual understanding of implementation disparities. Our pragmatic, experimental design will expand the evidence base on both effectiveness and implementation of ECHO and contribute to the AHRQ mission by addressing modifiable risk factors to reduce disparities in the incidence of NEC; leveraging telehealth-delivered mentoring to facilitate adoption of EBP by removing accessibility barriers; and offering at-the-shoulder support for NICUs most in need. This application is responsive to the AHRQ Special Emphasis to Advance Health and Healthcare Equity (NOT-HS-23-013), informing the advancement of equitable neonatal healthcare quality using implementation science.

NIH Research Projects · FY 2025 · 2024-09

PROJECT SUMMARY Two-drug regimen (2-DR) containing potent second-generation integrase inhibitor (INI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) are currently available as oral formulation (dolutegravir-rilpivirine) and long-acting injectable nanosuspension (cabotegravir-rilpivirine) for HIV prophylaxis and therapy. Oral 2-DR tablet (Juluca; dolutegravir-rilpivirine) is equally effective but with significantly lower adverse effects compared to the three-drug regimen based on 2 NRTIs. However, dolutegravir (DTG) and rilpivirine (RPV) both have pH dependent solubility, low oral bioavailability and long-term use of INI can lead to metabolic diseases including diabetes. Given the need for lifelong administration of these drugs, strategies that can improve the oral bioavailability of DTG and RPV are highly desirable for optimal drug utilization and to achieve a reduction in therapeutic dose and dose-related side effects. While the intramuscular long-acting cabotegravir-RPV nanosuspension is highly effective in the long-term management of HIV infections, there is a strong need to develop a non-invasive, strategy that can allow for self-administration and long-term HIV therapy. The non- invasive transdermal route is yet to be explored for the delivery of 2-DR containing INI and NNRTI. Ionic liquids (ILs) are low-melting organic salts with a melting point < 100°C and pharmaceutically acceptable fatty cations and/or anions can be used to develop amphiphilic ILs with excellent drug solubilization capacity. Pharmaceutically acceptable cations and fatty anions can be assembled into amphiphilic ILs with excellent biocompatibility and drug solubilization capabilities. We hypothesize that carnitine, a generally regarded as safe (GRAS) cation and fatty anionic permeation enhancers with GRAS status can be assembled to develop amphiphilic ILs with excellent solubilization capacity for hydrophobic drugs such as DTG and RPV and that subsequent incorporation of these ILs into oral lipid-based formulations (LBFs) such as self-nanoemulsifying systems (SNES) and transdermal LBFs such as nanoemulsion-based gel will improve oral and transdermal delivery of DTG-RPV combination. Our preliminary data show that a co-processed mixture of DTG and RPV has very high solubility (RPV: ~ 166 mg/g and DTG: 334 mg/ml) in amphiphilic carnitine IL (carnitine salcaprozate) and carnitine salcaprozate containing DTG-RPV mixture showed significantly higher in vitro permeability through skin mimicking Strat-M membrane compared to DTG-RPV suspension. Aim 1 will focus on the development, characterization, and in vitro evaluation of nanoemulsion of carnitine ILs containing DTG-RPV combination suitable for oral and transdermal delivery. Aim 2 will focus on the pharmacokinetic evaluation of oral and transdermal lipid nanoformulations of carnitine IL containing DTG-RPV combination in healthy mice to establish the proof of concept. The successful completion of this proposal will lead to the development of pharmaceutically viable formulations containing INI based 2-DR to achieve effective long-term management of HIV infection in a non-invasive manner and this strategy can be expanded to other antiretroviral drug combinations.

NIH Research Projects · FY 2025 · 2024-09

Project Summary Globally, human papilloma virus (HPV) causes 5% of cancers and 30% of head and neck squamous cell carcinomas (HNSCC). While HPV is the most common sexually transmitted infection, most infections are cleared by the innate immune system. Only long-term infections, occurring when the virus evades the innate immune system, can become cancerous. HPV oncoproteins, specifically E6 and E7, may increase HPV persistence by disrupting innate immune pathways such as cGAS/STING. The cGAS/STING pathway senses cytosolic double stranded DNA (dsDNA) and initiates a type I interferon (IFN) response, which can promote immune clearance of the virus. Upon sensing dsDNA, cGAS combines ATP and GTP to generate cGAMP which activates STING, ultimately resulting in the production of type I IFNs. Given that IFN has antiviral and antitumor properties, HPV likely evolved to counteract this pathway. Indeed, there is evidence that HPV oncogenes evade and manipulate the cGAS/STING pathway. However, HPV may generate several different types of cytosolic DNA; it can induce genomic DNA damage, may be shuttling viral DNA into the cytosol, and has been correlated to increased mitochondrial DNA copy number. While these damage associated molecular patterns can activate the cGAS/STING/IFN pathway, this has not been demonstrated in the case of HPV infection. Despite uncertainty as to the source of cGAS/STING pathway activation in HPV(+) cells, pathway suppression is clearly important. Our preliminary data, working with full-length and recombinant HPV genomes in primary patient-derived keratinocytes, indicates that HPV infection reduces the activation of the cGAS/STING/IFN pathway when exposed to exogenous DNA. I demonstrate that HPV E6 expression promotes STING degradation. In parallel, I demonstrate that, despite interfering with pathway activation, HPV(+) tonsil cells have increased baseline cGAMP production compared to HPV(-) patient-matched tonsil cells, raising the question of what is activating cGAS in HPV(+) cells. I hypothesize that HPV causes genomic DNA damage leading to the production of cGAMP, and to circumvent this, E6 promotes STING degradation. To test this hypothesis, I will determine the mechanisms by which high-risk HPV E6 drives STING degradation as well as identifying the source of nucleic acids causing cGAS activation in HPV(+) cells. Aim 1 of this proposal will assess the rate of STING degradation, how it is impacted by HPV E6, and the contribution of two E3 ubiquitin ligases on STING degradation. Aim 2 will identify the source of cGAS-activating nucleic acids present in HPV(+) tonsil cells and HPV(+) head and neck cancer tumors as well as the contribution of mitochondrial and genomic DNA damage on cGAS activation. Completion of the proposed studies will provide greater understanding of how the HPV oncogene E6 impacts STING degradation. It will also identify the source of nucleic acids activating cGAS in HPV(+) tonsil cells. Additionally, this work will provide me with valuable tools and training to prepare me for a career in immunology, virology, and cancer research after graduate school.

NSF Awards · FY 2024 · 2024-09

Proteins drive much of the chemistry of life. They control many of the reactions that allow organisms to survive, and they are essential structural elements that determine life’s form. All proteins are long chains of subparts called Amino Acids of which there are 20 common types. Substitution of one amino acid for another may have either a small or a large effect on the form and function of a protein. Knowing the probability of substituting one amino acid can help determine the evolutionary history of a protein. This research will improve our estimates of the substitution probabilities between the common amino acid. This information will then improve software that is essential for reconstructing the tree of life. The project will train multiple students in statistics and data science. In addition, outreach activities will improve science literacy by promoting critical use and editing of online information sources. This research will improve the inference of amino acid substitution models by excluding likely alignment errors from training data. Analysis of taxon-specific differences in protein evolution should then be revealed by the removal of universal artifacts. Training of amino acid substitution models on data specific to different types of protein structural characteristics will also improve understanding of substitution probabilities by uncovering how different structural types of proteins evolve. The resulting structure-informed mixture and/or partition models can then be used to improve phylogenetic inference. The methods develop will allow for changes in amino acid frequency over time. These methods will be validated by comparison of predictions and experimental effects. 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 · 2024-08

PROJECT SUMMARY Hispanic women are up to 70% more likely to experience infertility (i.e., trying to conceive for ≥12 months without success), compared to non-Hispanic white women in the US (NHWW). Recent studies indicate that women with a history of infertility may be at greater risk of cancer, cardiometabolic diseases, and mortality later in life and that risk may vary among specific infertility diagnoses (e.g., endometriosis, tubal factor infertility, and polycystic ovary syndrome). Prior research has shown that the severity, incidence, and risk factor profiles for cancer, cardiometabolic diseases, and mortality differs between Hispanic women and NHWW. However, there has been a paucity of research on infertility and long-term health outcomes among Hispanic women, despite Hispanics being the largest minority group in the US with two-thirds having Mexican heritage. Our proposal will utilize the Mexican Teachers´ Cohort (MTC), a prospective cohort study of 115,306 women from 12 geographically diverse states in Mexico who were a median age of 44 (range 20-84) when the cohort began in 2006-2008. MTC has collected data for 18 years. The MTC will harnesses detailed data on reproductive health, including information on specific infertility diagnoses (e.g., PCOS, ovulatory, tubal, endometriosis, male factor), infertility treatments, and pregnancy history. The cohort has validated information on disease endpoints including breast cancer, ovarian cancer (recently funded by NCI), diabetes, and mortality through linked electronic health records and a national mortality registry through 2019. In the planned proposal, we will leverage our successful methodology to validate incident breast cancer, diabetes, and mortality cases (2019-2024), and identify and confirm endometrial cancer, ischemic heart disease and stroke cases (2006-2024). Specifically, our proposal will: Aim 1. Determine the risk of cancer for women with a history of infertility compared to parous women without infertility; Aim 2. Determine the risk of cardiometabolic diseases for women with a history of infertility compared to parous women without infertility; Aim 3. Determine the risk of premature mortality for women with a history of infertility compared to parous women without infertility. The chronic disease risk for Hispanic women with infertility is not known despite their high infertility disease burden and unique chronic disease profile. This gap in knowledge precludes them from benefitting from early screening and interventions which may ultimately reduce morbidity and mortality. This proposal, utilizing a large, well-characterized resource of women with Mexican heritage, is the first step towards filling a substantial gap in understanding risk of long-term health outcomes among Hispanic women, the largest minority group in the US.

NIH Research Projects · FY 2025 · 2024-08

Project Summary/Abstract: Adverse childhood experiences (ACEs) are strongly associated with cardiometabolic and mental health outcomes in adulthood. Mechanisms of this relationship are thought to be varied, including both behavioral and physiological pathways. Similarly, intergenerational trauma (IT), has also been linked to adverse cardiovascular health (CVH) and mental health outcomes through both behavioral and physiological pathways. Both ACEs and IT are prevalent in Hispanic populations, factors associated with IT (e.g., colonization, militarization, victimization) are especially prevalent at the US-Mexico border, and Hispanic populations are disproportionately impacted by other social determinants of health such as psychosocial stress and socioeconomic disadvantage and may be at higher risk for poor CVH outcomes. However, prevalence of ACEs/IT, factors associated with IT, and mechanisms linking ACEs/IT to CVH at the US-Mexico border remains understudied. Understanding these relationships would address a critical gap in the literature and potentially elucidate intervention strategies towards eventually reducing or eliminating CVH disparities at the US-Mexico border. The proposed study will investigate the role of ACEs/IT in relation to CVH and risk factors in a unique, understudied population using comprehensive, validated approaches. It is hypothesized that presence of ACEs and/or IT is associated with worse CVH, and that the relationship is impacted by social, behavioral, and physiologic risk factors. The study aims to determine the relationship between ACEs/IT and CVH components (Research Aim 1), establish the relationship between ACEs/IT and risk factors (acculturation, psychosocial stress, socioeconomics, and/or neurocognitive factors) (Research Aim 2), and evaluate the role of proposed risk factors in the relationship between ACEs/IT and CVH among Hispanic adults of Mexican descent living at the US-Mexico border. The proposed study will examine n=50 Hispanic adults of Mexican descent living at the US-Mexico border who are recruited for the sponsor’s Sleep and Cardiometabolic Health Disparities at the US/Mexico Border: The Nogales Cardiometabolic Health and Sleep (NoCHeS) study. The study will use validated questionnaires to measure ACEs and IT. CVH will be assessed utilizing the newly released Life’s Essential 8 (LE8) metric by the American Heart Association (AHA). All metric components will be measured using standard, objective, and self-report measures in a clinic visit and at home. Additionally, potential behavioral and physiologic mechanisms will be explored, including acculturation, psychosocial stress (stress and social support), socioeconomics, and neurocognitive factors (processing speed, executive function, working memory, inhibitory control). Findings will increase understanding of the relationship between ACEs, IT, CVH and risk factors in this population. Finally, this study will serve as a foundation for future translational research aimed at prevention and intervention strategies for potentially modifiable risk factors in CVH and will provide the applicant with necessary training to further pursue community-engaged, independent research focused on reducing health disparities and improving health through practical, data-driven solutions.

NSF Awards · FY 2024 · 2024-08

Since the invention of computer-aided tomography, numerous imaging modalities have been introduced and have demonstrated increasing value as diagnostic instruments in biology and medicine. These include Thermoacoustic and Photoacoustic Tomography (TAT and PAT), Magnetoacoustoelectric Tomography (MAET), and UltraSound Current Density Imaging (USCDI), which combine the high resolution of ultrasound with the sensitivity of electromagnetic waves to optical absorption and conductivity of the tissues, or to biological currents in the heart or in the brain. Sharp abnormalities in the latter physical parameters are good markers of breast cancer, thrombosis, ischemia, epilepsy and other medical conditions. These new techniques overcome limitations of classical tomography, and deliver otherwise unavailable, potentially life-saving diagnostic information — at a lesser cost and with less harm to a patient. The images in these modalities are obtained by complex mathematical procedures, rather than through direct acquisition. The underlying mathematics and the image reconstruction algorithms required by these methods are at very early stages of development. The investigator, in collaboration with domain scientists and medical engineers will work to resolve some of the central theoretical challenges and develop efficient numerical techniques for PAT, TAT, MAET and UCSDI. A graduate student will play a significant role in the project, gaining exposure to practical and theoretical skills lying at the junction of exact sciences, medicine, and biology. The results of this project will be disseminated through publications in high quality research journals, presentations at national and international conferences, and a series of lectures at various major venues. The algorithms and the experimental data will be made publicly available. The mathematics underlying and enabling such modalities as PAT, TAT, MAET and UCSDI scattering, contains a number of challenging open questions, important from both the theoretical and applied points of view. The investigator, with his graduate student and colleagues at several universities, aims to gain theoretical understanding and to develop efficient image reconstruction algorithms for these modalities. In particular, they plan to (1) derive range conditions for the wave operator arising in TAT and PAT, defined on a spherical domain with a reduced measurement interval, (2) develop fast algorithms enabling deep learning techniques in data-intensive inverse problems of TAT and PAT (3) and on deriving, justify and explore an accurate model of ultrasound current detection in acoustically perturbed medium. 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

This project will contribute to the national need for well-educated scientists, mathematicians, engineers, and technicians by supporting the retention and graduation of high-achieving, low-income students with demonstrated financial need at the University of Arizona (UArizona), a public, land-grant, Hispanic-Serving Institution (HSI). With multiple rural and urban campuses, UArizona serves Southwestern regions across the Arizona, California, and Mexican borders, where there is a significant need for engineers to meet agricultural, energy, semiconductor, and military industry demands. Yet, due to financial and sociocultural factors, a large proportion of individuals in these communities have limited access to high quality postsecondary education. Over its six-year duration, this project will provide scholarships to up to 50 undergraduate students who are pursuing bachelor’s degree in an engineering discipline at UArizona. Transfer students will receive up to three years of scholarship support, while those who are directly starting their four-year degree at UArizona will receive up to five years scholarships. In addition to receiving scholarships, students will develop and maintain a portfolio of their academic, cultural, and personal strengths and experiences. This individualized portfolio will serve as the primary resource to provide targeted support services including strengths-based academic advising, mentorship from engineering faculty, and internship and job placements in engineering positions. The overall goal of this project is to increase STEM degree completion of low-income, high-achieving undergraduates with demonstrated financial need. The primary objectives are (1) to improve persistence, retention, and graduation rates and placements in engineering among eligible students from rural and urban campuses using intentional asset-based practices, and (2) to investigate differences in assets, outcomes, engineering identities, and placements between students at a rural campus and those at an urban campus. The central tenet of this project is the process of discovering, mapping, and applying students’ assets for their professional development and success in engineering. A rigorously designed mixed methods study will generate knowledge on how students identify and activate their assets to succeed in engineering programs and ways in which asset-based practices influence outcomes and identities of engineering students attending at rural versus urban campuses. This project is thus a unique opportunity to increase our knowledge about supporting students in economically distressed communities, expand our understanding of asset-based practices, and develop new insights into implementing such practices at minority-serving institutions, particularly HSIs. Results from this project will be disseminated both regionally through the state-wide HSI consortium and nationally through professional venues dedicated to engineering education. This project is funded by NSF’s Scholarships in Science, Technology, Engineering, and Mathematics program under the ETSTE DCL, in partnership with Intel Corporation. The program seeks to increase the number of low-income academically talented students with demonstrated financial need who earn degrees in STEM fields. It also aims to improve the education of future STEM workers, and to generate knowledge about academic success, retention, transfer, graduation, and academic/career pathways of low-income students. 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

Leading edge bubbles on airfoils are mostly created by laminar separation followed by transition to turbulence that results in reattachment. They may be long, but they are usually shallow. They are associated with low Reynolds numbers and are generally avoided by trip strips or vortex generators. Leading Edge Vortices (LEVs) have to be considered differently as they contribute substantially to lift on delta wings and swept-back thin wings at high Reynolds numbers and at high operational incidence angles. The liftoff of LEVs and their path over the wing has a major effect on trim, thus limiting the operational incidence of airplanes. The goal of the proposed study is to understand the interior structure of a large LEVs that is not encumbered by complex wing design, and to create a theoretical model capable of explaining some recently made observations. It is believed that the LEV structure could be explained by separating the flow into components, one being normal and another tangential to the leading edge. Both represent mixing layers that are susceptible to Kelvin-Helmholtz instability, but they differ with the normal component being perhaps absolutely unstable while the spanwise one may only be convectively unstable. If this is proven experimentally, it will provide a tool for flow control consisting of a small source of periodic excitation located near the apex. Theoretical criteria could then follow and account for the unsteadiness and lack of stationarity. A single steady jet can deflect the LEV either upward or sideways and generate large differences in pitch that is either positive or negative (nose-up or down). It therefore provides a paradigm shift in the control of tailless aircraft configurations. A simple, flat plate cranked wing model with a sharp leading edge being beveled from the bottom surface would provide some fundamental information about this flow, but there is a lot to be understood to achieve the benefits. This configuration eliminated many secondary independent variables such as a leading-edge radius or outwash that muddied the results in the past, making the study less definitive. Since the amplification of the Kelvin-Helmholtz vortices is inviscid and the separation line is fixed by the sharp leading edge, the study is almost independent of Reynolds number and the wing does not require trip-strips. Periodic zero-mass-flux perturbations emanating from a point source will be introduced near the crank in addition to the steady jets that were already tested, and their growth along the span will be monitored because it should affect first the convective instability along the span. Measurements will include first phase locked time resolved 3D particle image velocimetry data that is complemented by the occasional use of hot-wires and flow visualization. Surface pressures with some time resolved pressure data should also be taken. These results could lead to theoretical approaches used to better understand and control turbulent mixing layers, jets, and wakes. 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 incidence of extreme heat events has increased in frequency and intensity in the last century as global temperatures have risen, driven by anthropogenic greenhouse gas forcing. When extreme heat occurs at the same time as drought, the impacts are exacerbated. These "hot drought" events have complex consequences for communities across North America, including altered water resource availability and fire regimes, as well as the magnitude of the uptake of carbon dioxide by forests. This project will compile new and previously collected temperature reconstruction data from tree cores from across North America into a "North American Temperature Atlas," which will allow for the analysis of relationship of heat and drought at a range of time and spatial scales. The goals of this project are to make new blue intensity measurements on previously collected tree cores from North America, compile existing blue intensity and maximum latewood density tree ring chronologies from North America, and combine the new and existing datasets together to create the “North American Temperature Atlas” (NATA), a gridded reconstruction of warm season surface air temperature. The NATA will be compared to a gridded North American drought atlas and a gridded North American seasonal precipitation atlas to determine the contribution of temperature to past droughts, evaluate the temperature-drought relationship, and place the modern occurrence of drought in the context of the last several centuries. The Broader Impacts are to create a web interface for public access to the NATA, support for graduate students at University of Tennessee, Knoxville, and University of Idaho, development of outreach to water and natural resource managers, creation of K-12 STEM activities for middle school students, tours of tree ring lab for K-12 students, mentoring high school and undergraduate students underrepresented in STEM on projects related to this work. 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

Project Summary/Abstract This application is in response to NOT-OD-23-166, PAR-21-358, and aligns with NIMHD's key areas of interest including family health and well-being for SGM adolescents. Family acceptance and support are critical factors that promote resilience and reduce mental health burden among sexual and gender minority (SGM) adolescents. The existing knowledge base on family relationships among SGM adolescents is limited in generalizability beyond predominately non-Latinx, White samples, and is often based on perspectives of one family member (either SGM adolescents or their parents). Yet, cultural strengths and stressors influence family relationships and resultant health of multiple family members. Framed by the SGM Health Disparities Research Framework and the Family Health Development Integrative Model, this study, through a multistage and multimethod design, seeks to understand intersectional family relationships and how they contribute to mental health among Latinx SGM adolescents and their parents. Culturally-informed qualities of family relationships are examined as direct contributors to family health and as potential targets for future intervention development to mitigate the harmful contributions of structural and social determinants of health for Latinx SGM adolescents and their parents. In Aim 1, Latinx SGM adolescents and academic and community experts who work with Latinx SGM adolescents and their families will help adapt, test, and validate the existing parent-report measure of acceptance for Latinx SGM adolescents in order to establish an adolescent-report version of this measure (the Parental Acceptance for Latinx SGM Adolescents [PALSA] measure). This measure will allow for dyadic, multireporter and culturally-responsive understandings of family relationships among Latinx SGM adolescents and their parents. Aim 2 examines how family relationships from multiple reporters within families converge/diverge and how they predict Latinx SGM adolescent and parent mental health. SGM adolescents and a primary parent (N = 249 dyads) will be purposively recruited to ensure representation of SGM identities (i.e., cisgender sexual minority; trans/nonbinary gender minority) in two established immigrant destinations (i.e., Arizona and Florida). Aim 3 of the proposal extends Aim 2 findings to understand how family relationships moderate the associations between structural and social determinants of health and key mental health outcomes. Aims 2 and 3 collectively will reveal unique strengths and barriers in Latinx families with SGM adolescents to inform targets to ameliorate SGM adolescent and parent mental health burden. The dyadic measures optimized in the study can be used to help facilitate resilience in Latinx families with SGM adolescents by community and clinical providers.

NIH Research Projects · FY 2025 · 2024-08

PROJECT SUMMARY The effective long-term management of HIV infection in pediatric patients faces a multitude of challenges such as lack of age-appropriate pediatric formulations, high pill burden, unavailability of oral liquid formulations, poor palatability of existing pediatric formulations, forgetfulness, and emerging independence in adolescents. These challenges and psychosocial, behavioral, and socioeconomic barriers and health disparities have led to poor adherence and only ~50% of children living with HIV are able to receive antiretroviral therapy. While the intramuscular long-acting cabotegravir-rilpivirine (RPV) nanosuspension is highly effective in the long-term management of HIV infections in adults and adolescents, there is a strong need to develop a non-invasive, room temperature stable formulation that can allow for self-administration, high adherence and long-term HIV therapy in children and adolescents affected with HIV. The non-invasive transdermal route is yet to be explored for the delivery of potent second-generation antiretroviral drugs. Our preliminary study showed that dolutegravir (DTG) has a great potential to be delivered as a transdermal formulation compared to cabotegravir whereas rilpivirine, due to its high crystallinity and low aqueous and lipid solubility was not amenable for transdermal delivery. Ionic liquids (ILs) are low-melting organic salts with a melting point < 100°C and pharmaceutically acceptable fatty anionic permeation enhancers can be used to develop amphiphilic ILs with excellent drug solubilization capacity, lipid solubility, and transdermal permeability. We hypothesize that rilpivirine (RPV) and generally regarded as safe (GRAS) fatty anionic permeation enhancers can be assembled to develop amphiphilic RPV ILs with excellent lipid solubility and solubilization capacity for DTG and that subsequent incorporation of RPV IL(s) and DTG into transdermal lipid-based formulations such as nanoemulsion-based gel will improve transdermal delivery of DTG-RPV combination. Our preliminary data show that a prototype nanoemulsion containing IL of RPV (RPV docusate) and DTG combination showed significantly higher in vitro permeability of RPV and DTG through skin mimicking Strat-M membrane compared to DTG-RPV suspension. Aim 1 will focus on the development, characterization, and in vitro evaluation of nanoemulsion-based gel formulations containing various RPV ILs and DTG combination suitable for transdermal delivery. Aim 2 will focus on the pharmacokinetic evaluation of transdermal nanoemulsion-based gel containing RPV IL and DTG combination in NSG mice to establish the proof of concept. Aim 3 will evaluate the in vivo antiretroviral efficacy of nanoemulsion-based gel containing RPV IL and DTG combination in a humanized mouse model of HIV infection. The successful completion of this proposal will lead to the development of pharmaceutically viable formulations containing combination antiretroviral drugs for effective long-term management of HIV infection in pediatric patients in a non-invasive manner and this strategy can be expanded to other antiretroviral drug combinations.

NIH Research Projects · FY 2024 · 2024-08

Abstract The role of glymphatic system for brain health has been established in recent studies. Specifically, the removal of brain waste from the brain parenchyma through the cerebrospinal fluid (CSF) circulation is the key mechanism for maintaining brain health, and compromise of glymphatic activity is associated with neuropathological conditions (e.g., Alzheimer’s disease, Parkinson’s disease, traumatic brain injury). It is of great interest to identify interventional approaches to enhance glymphatic activity, specifically the CSF circulation. The goal of this study is to modulate glymphatic activities through the use of oscillating electromagnetic field, at the slow wave frequency (typically observed in non-REM sleep and anesthetized states) that enhances CSF movement and brain waste clearance. The proposed animal study in pigs, if successfully completed, is expected to create a new glymphatic modulation paradigm (translatable to humans) with significant implications for brain health improvement and intervention of neurological disorders. In aim 1 of the study we plan to measure the global impact of slow wave entrainment on brain waste clearance. Sub-aim 1-1: We will use MRI-gradient-based neuromodulation (termed MRI-stim) to achieve slow- wave entrainment in propofol-anesthetized pigs, and then assess glymphatic activity improvement through analyzing brain waste clearance in CSF samples (Aβ1-42, Aβ1-40, total tau, and phosphorylated tau). Sub-aim 1-2: We will use TMS-based slow-wave entrainment to modulate glymphatic activity, and assess changes of brain waste clearance in CSF samples. Exploratory sub-aim: We will perform an exploratory study that compares brain waste levels (measured from CSF samples) before and after applying glymphatic modulation to pigs with pharmacologically induced elevation of amyloid beta level in the brains (specifically, with intravenously injected amyloid beta entering brains through pharmacologically compromised blood-brain barrier). EEG signals will be concurrently measured to confirm brain wave entrainment. In aim 2 we will measure the regional impact of slow wave entrainment on brain and glymphatic physiology. Sub-aim 2-1: we will use unified MRI-stim and imaging pulse sequences, that are capable of achieving slow-wave entrainment as well as acquiring multi-contrast MRI data, in pigs anesthetized with propofol. Multi-contrast MRI data (dynamic diffusion MRI; phase-contrast MRI and ferumoxytol-based T2*- weighted MRI) will be acquired at multiple time points before and after slow-wave entrainment, so that neuromodulation induced dynamic changes in glymphatic activity (reflecting influx and clearance of CSF and ISF) can be quantified. EEG and ECG data will be concurrently obtained throughout the neuromodulation- neuroimaging sessions. Sub-aim 2-2: we will use our MRI-compatible TMS-based slow-wave entrainment to enhance glymphatic activity in propofol-anesthetized pigs, and measure changes in glymphatic physiology with multi-contrast MRI.

NIH Research Projects · FY 2025 · 2024-08

Over half of adolescents with Down syndrome (DS) have difficulty being understood by others which negatively impacts their engagement in daily life activities that require communication (i.e., communicative participation). Restrictions in communicative participation are not trivial and lead to un- and underemployment and loneliness which, in turn, lead to poor mental and physical health outcomes. Despite the urgent need, interventions to improve speech production in adolescents with DS are rare. Thus, speech-language pathologists use treatments that are designed for adults, are not specific to the underlying impairment in DS, and do not consider the unique psychosocial issues faced by adolescents. The long-term goal of this line of research is to bring a precision medicine approach to the development of theoretically-driven, evidence-based, participation- focused interventions for adolescents with DS. As a first step, we will construct deep phenotypes of communicative participation for adolescents with DS. Current intervention approaches focus exclusively on the underlying impairment while ignoring both the adolescent’s perspective and the societal structures that contribute to their disability. A key innovation of this proposal is the shift away from treating communicative participation solely as an impairment-level issue and toward a model of communicative participation that encompasses a broader view of functioning. To do so, we will employ the conceptual framework detailed in Baylor (Co-I) and Darling-White (PI; 2020) that models communicative participation as a biopsychosocial construct comprised of the following elements: communication skills (e.g., the underlying impairment), personal perspectives (e.g., preferences, coping), and communication environment (e.g., physical, social). Each element contributes to restrictions in communicative participation and warrants full consideration in intervention design and implementation. A critical barrier to the development of participation-focused interventions for adolescents with DS is the lack of empirical information regarding these elements, leaving us with a limited ability to identify intervention targets, measure progress, and facilitate lasting change. The first specific aim of this proposal is to construct impairment-level speech production profiles for adolescents with DS. The second specific aim is to investigate how personal perspectives and communication environment alter communicative participation for adolescents with DS. The third specific aim is to develop a mechanistic model of communicative participation for adolescents with DS. The expected outcome of this proposal is the deep phenotyping of communicative participation for adolescents with DS. By applying a precision medicine approach within a biopsychosocial framework, this proposal will lay the foundation for the creation of intervention that centers the patient perspective, addresses the underlying impairment based on comprehensive speech production profiles, and engages societal structures that contribute to disability.

NSF Awards · FY 2024 · 2024-08

Subduction has pushed carbonate platforms, like those in the Tethyan ocean, into the Earth. This caused a lot of carbon to move from the surface to the interior. The fate of those carbonate platforms in the Earth’s upper mantle is key. It helps in understanding the amount of carbon returned to the Earth’s surface by volcanic outgassing. It also helps in understanding the carbon that has stayed in the Earth’s mantle. It is expected that carbonate in platforms will rise from the slab to the Earth's crust when it is subducted, as the researchers found in their previous study. This likely results in a large fraction of the carbon returning to the Earth’s surface and would impact the paleoclimate. This study will test if subducted carbon ends up in the atmosphere from volcanoes. It will analyze the geochemical fingerprints of subducted marbles and the volcanic products in the rocks of the Carpathian region. Lab experiments will model what happens to the carbon that is subducted into the Earth to understand how the marble's geochemical signatures may change. This will happen when they are subducted and mix with the rocks in the Earth's mantle. The researchers will search for the changed chemical fingerprint in the Carpathian volcanic rocks. This will show whether subducted marbles were at the source of the volcanoes. It will also show how carbon returned to the Earth's surface after subduction. The study aims to improve the understanding of the behavior of carbon and focuses on its movement between the surface and interior of the Earth due to plate tectonics through Earth’s history. The researchers will make a mini documentary which will cover carbon's journey from the Earth's surface to its interior and back. It will have sections on regional geology, will cover the usefulness of high pressure-temperature experiments, and how they are useful for solving key geological problems. The documentary will be shared on YouTube and will be promoted through social media and local organizations, such as high schools, the Tucson Gem and Mineral Society, and others. A major sink of the global carbon cycle is subduction into the mantle. Some of that carbon returns to the surface or the crust via magmatism, although the quantification of those budgets is difficult and so far, uncertain. Subduction margins and convergent tectonics sensu lato are major players in the overall budget of carbon circulation at geologic time scales. Carbonate can be present in the oceanic lithosphere as (1) veins and relatively small volume layers in the crust and lithospheric mantle but also (2) as larger carbonate platforms under certain subduction margins. Whereas the first scenario leads to sizable carbon recycling over time, subduction of large platforms have the potential to return an order of magnitude more carbonate material than in the first case. The metamorphic changes and possible melting reactions of minor carbonate masses into larger silicate sedimentary cover or basement have been investigated to a fair extent. However, little is known when large carbonate masses as platforms are being subducted, a scenario that may have been rather common in the geologic history during the evolution of the various branches of the Tethyan ocean. This study will provide new key constraints on the fate of carbonate as it subducts in the form of carbonate platforms using the Carpathian region in the Alpine Tethys as the study location. Impure marbles, arc volcanics, peridotite and pyroxenite xenoliths will be analyzed for major and trace elements as well as Sr, Nd, Pb and Ca isotopes. The goal is to (a) obtain a range of geochemical and isotopic compositions of subducted marbles, (b) identify geochemical fingerprints of a sedimentary carbonate component in the volcanics and lithospheric samples. Phase equilibria experiments will be performed to investigate the partial melting behavior of impure marbles under sub-arc conditions and assess the fate of reactive infiltration of these partial melts through the sub-arc lithosphere. The thermal conditions at which partial melting likely takes place upon subduction of carbonate platforms will be noted, and the melt and residue compositions (and mineralogy) will be compared with the natural data. The goal is to assess whether subduction of carbonate platforms and consequent diapirism (as predicted by the researcher's previous study) govern the evolution of the lithosphere and magmatism in the Carpathian region and if the products from this study can be used to place constraints on carbon budgets due to subduction-lithosphere interaction. A mini documentary on deep carbon cycling with sections focusing on regional geology and the usefulness of high pressure-temperature experiments in tackling first order geological problems will be developed. The documentary will be disseminated to the public through YouTube and publicized through social media and local organizations such as high schools, the Tucson Gem and Mineral Society and others. 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

This award provides support for the Arizona LaserChron Center (ALC), which is an NSF Community Facility that utilizes LA-ICPMS to determine U-Th-Pb ages, Hf isotope ratios, and trace element abundances from minerals that occur in sedimentary, igneous, and metamorphic rocks. Primary goals of the ALC are to (1) generate information of optimal precision, accuracy, and spatial resolution, (2) provide opportunities for researchers from around the world (and especially NSF-supported scientists) to use our instruments and expertise to address geologic problems, (3) drive the development of new analytical methods and applications, (4) build new cyberinfrastructure, and (5) use every aspect of facility operation as an opportunity to enhance expertise among geochronologists and users of geochronology. The ALC supports NSF-funded research in Earth Science, Planetary Science, Archaeology, Materials Science, Natural Hazards, and Geological Engineering. Information is provided to constrain the timing and rates of processes such as crustal genesis, mountain building, generation and distribution of sediments, formation of critical elements and hydrocarbon resources, evolutionary change, paleoclimate, natural disasters, and linkages between climate, tectonics, and human activities. ALC data are reported in ~100 peer-reviewed publications per year, with an additional ~50 publications per year which utilize our software to handle data from other laboratories. The ALC collaborates with ~380 researchers per year, including faculty members, research scientists, post-docs, graduate students, and undergraduate students. Most facility users come to the lab to generate the data needed for their projects and learn about data processing and interpretation. Research by early-career scientists are prioritized. 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

This doctoral research investigates how multicultural communities negotiate their identities following migration. Over the last thirty years, archaeologists have expanded the study of migration from a topic limited to identifying the movement of people, to one that explores the different forms of interaction between local and migrant populations over time. Archaeology is well-placed to assess change over time in the interactions of local and migrant populations at various group sizes. By studying material culture, archaeology can address the extent to which migrants remained distinct versus becoming integrated into the newly formed multicultural communities. This is of particular concern now, as national and transnational migration is a current topic of discourse worldwide. Although migration is often framed as a "problem" to be solved, the investigators emphasize that migration is not a problem but something that humans have always done and always needed to navigate. In particular, this work contributes to how people navigate identity in multicultural communities. Additionally, this work funds an undergraduate research assistant, helping them understand and experience the research process by doing archival and museum collections work. The project examines how corrugated ceramics, or hand-built vessels with exposed coils, were used as a form of identity negotiation after a large migration of late prehistoric people. These ceramics are examined to address the question of whether migrants and hosts remained distinct groups or alternatively formed more cohesive communities. The researchers use these vessels to identify communities of potters at past settlements by looking at the technological and stylistic characteristics of each vessel. When examined together, subtle characteristics of a vessel create a "signature" for a potter or potting community because people learned to make these vessels differently. The investigator looks at vessels and archives from six archaeological sites before and after the migration. These sites were excavated from the 1940s to 1990s. The data set created by this analysis examines how pots were made at different sites and even within the same site before and after the migrations. These analyses reveal connections between the ways people were taught to make vessels across the region and identify communities that make corrugated vessels similarly, informing the researchers about how potters who migrated into new areas integrated (or not) into their new community. The team will thus contribute knowledge regarding how social dynamics were navigated for comparison to other case studies around the globe. 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

This collaborative project aims to develop new distributionally robust quadratic optimization models and methodologies to seamlessly integrate highly uncertain renewable energy into power systems, thereby providing society with cleaner, more reliable, and cost-effective energy solutions. Distributionally robust optimization (DRO) has emerged as a leading framework for optimizing under uncertainty, which can ensure the satisfaction of specified requirements even under adverse distributions of random parameters. Despite its advantages, applying DRO to nonlinear optimization problems under uncertainty remains challenging due to their inherent complexity. Nonlinearity is prevalent across various critical real-world applications in the US economy, beyond just power systems. This collaborative project will bridge this pressing gap by formulating new DRO models tailored to the unique characteristics of power systems and developing computationally efficient approaches to solve DRO problems with quadratic constraints. The project aims to deliver practical solutions that benefit all stakeholders and end-user communities. Its broader impacts include: (i) integrating research and education at the University of Arizona (UArizona) and the University of Illinois Urbana-Champaign (UIUC) by involving undergraduate students in hands-on research, connecting results with practical applications to inspire STEM careers; (ii) enhancing graduate-level education at UArizona and UIUC with contemporary case studies; and (iii) facilitating technology transfer to other societally important industries in the US economy, such as finance and transportation, where effective management of high uncertainty is crucial. This project will utilize distributionally robust optimization to address two critical decision-making challenges in uncertain power systems: (1) alternating current optimal power flow, and (2) power-system generation planning and operations, both of which are inherently formulated as quadratically constrained quadratic programming (QCQP) problems. The research objectives and tasks include: (1) developing new conic reformulations for distributionally robust QCQP problems; (2) designing efficient algorithms that exploit the special structure of these conic reformulations; and (3) adapting and applying these solutions to effectively address key optimization challenges in uncertain, large-scale power systems. These advancements aim to significantly enhance the computational efficiency and practical applicability of DRO solutions in real-world operational settings. 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

Most insects carry bacteria that are inherited from their mothers and live within their cells. Some of symbiotic bacteria manipulate their insect hosts’ reproduction in ways that improves the reproduction of host insects carrying the bacteria. Some of these symbionts sabotage host sperm such that fertilized eggs laid by females without the bacterium die early in life (“cytoplasmic incompatibility,” or “CI”). Of the five bacteria known to cause CI, Wolbachia is best studied, yet Cardinium hertigii, the focus of this study, causes CI without the same genes Wolbachia uses. The overall goal of this proposal is to discover the molecular mechanism by which Cardinium causes CI. The project is expected to have important benefits: Cardinium targets animal cell division, a fundamental process that can be better understood when agents that interfere with it are studied. In addition, CI-causing bacteria may be used for pest or vector management. The CI-causing Wolbachia reduces host susceptibility to viruses of insects that carry it, and is currently being introduced to mosquito populations around the world to reduce vector-borne viral diseases. This project will also engage elementary, high school and undergraduate students from under-represented groups in scientific education and research through outreach programs and research opportunities at all three institutions. Furthermore, a Citizen Science project led by The University of Arizona and North Carolina State University will engage amateur entomologists in research through their support in collecting and rearing parasitic wasps of whiteflies to census for Cardinium. Maternally inherited bacterial symbionts of arthropods that manipulate host reproduction profoundly influence host biology and evolution. Symbionts causing CI sabotage host sperm such that fertilized eggs of uninfected females die in early embryogenesis. The independent evolution of CI in Wolbachia and Cardinium represents a remarkable case of convergent evolution of a complex trait. In recent NSF-supported work, we identified two putative Cardinium CI genes in a Cardinium strain that infects a parasitic wasp of whiteflies, Encarsia suzannae. In three objectives we aim to determine the mechanism of CI in Cardinium: 1. Dissect the mechanism of Cardinium cEper1 CI candidate genes using an integrated study of localization, discovery of interacting host and Cardinium proteins, and mutation analysis. 2. Express genes in Drosophila to verify the role of these candidates in CI. 3. Identify CI genes of cEina3 causing CI in E. partenopea and compare to cEper1. Cardinium produces a virtually identical CI phenotype to Wolbachia with different genes. Study of Cardinium CI genes in the non-model Encarsia as well as heterologous models yeast and Drosophila will increase our understanding of both Cardinium and Wolbachia, by showing us which processes are common and which are unique, and by shedding light on core host processes vulnerable to manipulation. Given the interest of the scientific and public health communities in symbiont-based pest or vector-management strategies, a deeper understanding of host-symbiont interactions in the comparatively understudied Cardinium may also lead to new contexts for applications, or for applications in which Wolbachia is not effective. 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

This project will provide unprecedented insight into how different types of motile cells are able to detect gradients of chemicals (chemoattractants) and migrate towards the source, which is how many microorganisms find food and what guides immune cells to sites of inflammation or infection during the immune response in mammals. This important cellular behavior is termed chemotaxis and is not understood. Through an unknown mechanism, highly motile cells such as the amoeba Dictyostelium discoideum and mammalian white blood cells can detect a chemoattractant gradient that is as small as a 2% difference between the front and back of the cells, but how cells achieve such gradient sensing is not known. Using Dictyostelium as an experimental model, this project will uncover an important aspect of the gradient sensing machinery and how it functions to control the migration of cells. In addition, the project will strongly emphasize providing multidisciplinary research training, laboratory experiences, and mentorship to diverse high school and undergraduate students in both California and Arizona. This will be achieved through partnerships with local schools as well as the development of an undergraduate colloquium course aimed at preparing and engaging students in scientific research early in their undergraduate career. In Dictyostelium, the cAMP chemoattractant receptor cAR1 couples with heterotrimeric Gα2βγ protein (G2) to drive chemotaxis in response to cAMP. Evidence suggests the presence of G2 signaling asymmetry during chemotaxis, but the role of cAR1 in creating this signaling asymmetry and promoting gradient sensing is unclear. The proposed work addresses this important question, with the hypothesis that distinct receptor phosphorylation events modulate gradient sensing and subsequent activation of the polarized Ras chemotactic pathway by spatiotemporally altering cAR1-G2 interaction and G2 activation dynamics in a cAMP concentration-dependent manner. This hypothesis will be tested in two Specific Aims. Aim 1 will determine the role of cAR1 in gradient sensing and the chemotactic response through a combination of site-directed mutagenesis, biochemical assays, and quantitative imaging of live cells migrating in precise gradients produced by microfluidic devices. The resulting data will form the basis for creating mathematical models of gradient sensing and its modulation by cAR1 phosphorylation to identify underlying mechanisms. Aim 2 will define the cAR1-G2 interaction dynamics and role in chemotaxis using Bioluminescence Resonance Energy Transfer (BRET) methods in live Dictyostelium cells coupled to mathematical modeling, which will allow integrating the data in a comprehensive chemotaxis model combining results of both Aim 1 and Aim 2. Together, these studies will reveal how the chemoattractant receptor functions and how it is regulated to promote gradient sensing and dictate the downstream polarized chemotactic pathways that control the directed migration of cells. 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.