Wcu

NATIONAL CHILD WELFARE CAPACITY BUILDING CENTER FOR TRIBES

NATIONAL CHILD WELFARE CAPACITY BUILDING CENTER FOR TRIBES (CBCT)

HIGHER EDUCATION EMERGENCY RELIEF FUND UNDER CARES ACT - INSTITUTION PORTION

EMERGENCY FINANCIAL AID TO STUDENTS UNDER CARES ACT

OHIO HOSPITAL ASSOCIATION COVID-19 PREPAREDNESS AND RESPONSE ACTIVITIES

LEARNING TRAJECTORIES AS A COMPLETE EARLY MATHEMATICS INTERVENTION: ACHIEVING EFFICACIES OF ECONOMIES AT SCALE

MARRIAGE EDUCATION AND RISK REDUCTION FOR ARMY FAMILIES

PRENATAL HOSPITAL-BASED HEALTHY RELATIONSHIP EDUCATION

REDUCING FETAL EXPOSURE TO MATERNAL DEPRESSION TO IMPROVE INFANT RISK MECHANISMS

CLOSE RELATIONSHIPS AND ADJUSTMENT IN ADOLESCENCE AND EMERGING ADULTHOOD

RELATIONSHIP EDUCATION FOR PREGNANT AND PARENTING TEENS AND YOUNG ADULTS

THE OPERATION OF THE CORRECTIONS TECHNOLOGY CENTER OF EXCELLENCE

REDUCING MATERNAL PRENATAL DEPRESSION TO IMPROVE CHILD CARDIOVASCULAR HEALTH - PROJECT SUMMARY/ABSTRACT IT IS CRITICAL TO UNDERSTAND RISK AND PROTECTIVE FACTORS FOR HEALTH TO OPTIMIZE DEVELOPMENTAL OUTCOMES AND INFORM PREVENTION OF POOR HEALTH BEHAVIORS ACROSS THE LIFESPAN. RESEARCH USING LONGITUDINAL DESIGNS, MULTIPLE LEVELS OF ANALYSIS, AND EXPERIMENTAL CLINICAL TRIALS ARE NEEDED. CARDIOVASCULAR DISEASE (CVD) IS THE LEADING CAUSE OF DEATH WORLDWIDE. THE ORIGINS OF ADULT CVD BEGIN PRENATALLY: HIGH PRENATAL MATERNAL DEPRESSIVE SYMPTOMS ROBUSTLY PREDICT OFFSPRING CVD RISK. HOWEVER, KNOWLEDGE ON RISK AND PROTECTIVE FACTORS FOR CVD FOR OFFSPRING OF MOTHERS WITH HIGH DEPRESSIVE SYMPTOMS HAS BEEN CORRELATIONAL. THERE IS A LACK OF EXPERIMENTAL WORK USING A RANDOMIZED CONTROLLED TRIAL (RCT) DESIGN TO UNDERSTAND POTENTIAL MECHANISMS THAT CONTRIBUTE TO CHILDREN'S CVD RISK FOLLOWING EXPOSURE TO HIGH MATERNAL PRENATAL DEPRESSIVE SYMPTOMS ACROSS MULTIPLE LEVELS (E.G., MATERNAL AND CHILD BEHAVIORS, PHYSIOLOGY) OVER TIME. ALTHOUGH EFFICACIOUS INTERVENTIONS TO DIMINISH DEPRESSIVE SYMPTOMS AMONG PREGNANT WOMEN EXIST, RESEARCH HAS NOT INVESTIGATED WHETHER REDUCING PRENATAL MATERNAL DEPRESSIVE SYMPTOMS CAN REDUCE OFFSPRING CARDIOVASCULAR RISK. THE CURRENT STUDY PROPOSES TO LEVERAGE A RCT OF AN EFFECTIVE PSYCHOSOCIAL INTERVENTION FOR PRENATAL MATERNAL DEPRESSION TO TEST WHETHER REDUCING PRENATAL MATERNAL DEPRESSIVE SYMPTOMS IMPROVES OFFSPRING CARDIOVASCULAR HEALTH AT AGES 3-4 YEARS. WE HYPOTHESIZE THAT THE PRENATAL INTERVENTION OPERATES BY REDUCING BOTH PRENATAL AND POSTNATAL DEPRESSIVE SYMPTOMS TO IMPROVE CHILD OUTCOMES. THIS STUDY WILL IDENTIFY INTERVENTION TARGETS FOR OFFSPRING OF MOTHERS WITH HIGH PRENATAL DEPRESSIVE SYMPTOMS TO REDUCE CARDIOVASCULAR RISK. THESE GOALS WILL BE ACCOMPLISHED BY BUILDING ON A RCT (R01MH109662) OF AN ESTABLISHED PSYCHOSOCIAL INTERVENTION THAT EFFECTIVELY REDUCES MATERNAL PRENATAL DEPRESSIVE SYMPTOMS. WE PROPOSE TO LEVERAGE THIS UNIQUE OPPORTUNITY TO FOLLOW UP MOTHERS AND CHILDREN WHO PARTICIPATED IN THIS RCT TO TEST WHETHER THIS INTERVENTION IMPROVES OFFSPRING CARDIOVASCULAR HEALTH. THIS PROJECT INCREASES RIGOR OF THE EXISTING CORRELATIONAL RESEARCH BY USING AN EXPERIMENTAL RCT DESIGN. THE FOLLOWING 3 AIMS WILL BE ADDRESSED. AIM 1: TO TEST WHETHER REDUCING PRENATAL MATERNAL DEPRESSIVE SYMPTOMS IMPROVES THE QUALITY OF FOOD THE MOTHER FEEDS HER CHILD, MATERNAL FEEDING BEHAVIORS, AND MODELING OF EATING BEHAVIORS AT 3 YEARS. AIM 2: TO TEST WHETHER REDUCING PRENATAL MATERNAL DEPRESSIVE SYMPTOMS IMPROVES CHILD DIET, EATING BEHAVIORS, SLEEP, AND PHYSICAL ACTIVITY AT 3 YEARS. AIM 3: TO TEST WHETHER REDUCING PRENATAL MATERNAL DEPRESSIVE SYMPTOMS REDUCES CHILD CVD RISK AT 3 AND 4 YEARS, INCLUDING BMI, WAIST CIRCUMFERENCE, BODY FAT, BLOOD PRESSURE, AND ARTERIAL STIFFNESS. THIS PROJECT WILL PROVIDE THE STRONGEST EVIDENCE TO DATE FOR A MECHANISTIC MODEL OF PRENATAL MATERNAL DEPRESSIVE SYMPTOMS' INFLUENCE ON CHILD CARDIOVASCULAR HEALTH. IMPORTANTLY, THE PROJECT WILL ALSO PROVIDE EVIDENCE FOR WHETHER EFFECTIVE PSYCHOSOCIAL INTERVENTIONS TO REDUCE PRENATAL MATERNAL DEPRESSIVE SYMPTOMS SHOULD BE USED TO REDUCE THE BURDEN OF CVD IN THE NEXT GENERATION.

EDUCATION RESEARCH PROGRAM

IDENTIFYING DETERMINANTS OF HIV-1 RESPONSIBLE FOR THE NANOSCALE DISTRIBUTION AND DYNAMICS OF VIRUS ASSEMBLY

EVALUATING THE EFFICACY OF AN INDERDISCIPLINARY PRESCHOOL CURRICULUM (EPIC)

GROUP-BASED PREVENTION OF POSTPARTUM DEPRESSION: IN-PERSON VS. VIRTUAL DELIVERY - PROJECT SUMMARY DEPRESSION IS ONE OF THE MOST COMMON PERINATAL COMPLICATIONS, WITH 1 IN 7 MOTHERS QUALIFYING FOR A DIAGNOSIS OF POSTPARTUM DEPRESSION (PPD) AND EVEN HIGHER RATES FOR THOSE WHO IDENTIFY AS HISPANIC/LATINE, BLACK OR AFRICAN AMERICAN, AMERICAN INDIAN, OR ALASKA NATIVE, OR BY MULTIPLE RACES OR ETHNICITIES. THIS PROJECT ADDRESSES THIS MAJOR GAP IN SERVICES TO PREVENT PPD, PARTICULARLY AMONG SOCIOECONOMICALLY DISADVANTAGED AND MINORITIZED GROUPS. IT TESTS THE BENEFIT OF A VIRTUAL PERINATAL PREVENTIVE INTERVENTION IN ENGLISH AND SPANISH TO INCREASE ACCESS, SCALABILITY AND ADDRESS THE MENTAL HEALTH NEEDS OF UNDERSERVED POPULATIONS. THIS PROJECT WILL TEST THE VIRTUAL VERISON AGAINST THE IN-PERSON VERSION OF A SERVICE-READY EFFICACIOUS PREVENTIVE INTERVENTION IN A RANDOMIZED CONTROLLED TRIAL (RCT). CONSISTENT WITH THE THIRD PRIORITY FROM RFA-MH-21-240, THIS EFFECTIVENESS TRIAL WILL PROVIDE A TEST OF A PREVENTIVE INTERVENTION WITH A STRONG EVIDENCE BASE THAT IS SCALABLE AND CAN BE DELIVERED WITH FIDELITY BY SERVICE PROVIDERS IN SETTINGS WHERE OBSTETRIC CARE IS RECEIVED. IN THIS PROJECT, PREGNANT WOMEN WILL BE RANDOMIZED TO RECEIVE AN EVIDENCE-BASED GROUP PREVENTION PROGRAM (REACH OUT, STAY STRONG, ESSENTIALS FOR NEW MOMS; ROSE) DESIGNED FOR PERINATAL POPULATIONS EITHER A) IN PERSON, DELIVERED AT THE HOSPITAL WHERE THEY ARE RECEIVING PRENATAL CARE OR B) VIRTUALLY, DELIVERED BY THE SAME STAFF VIA VIDEO CONFERENCING, BOTH OFFERED IN ENGLISH AND SPANISH. THIS PROJECT WILL TEST THE FOLLOWING AIMS: 1: TEST EFFECTIVENESS OF A VIRTUAL GROUP PREVENTIVE INTERVENTION PROGRAM ON REDUCING POSTPARTUM DEPRESSION COMPARED TO IN-PERSON DELIVERY. 2: IDENTIFY MECHANISMS OF CHANGE FOR THE INTERVENTION AND CHARACTERISTICS THAT PREDICT WHO RECEIVES THE GREATEST BENEFIT. 3: PROVIDE IMPLEMENTATION RECOMMENDATIONS FOR TRANSPORTING AND SUSTAINING PROGRAMS IN OTHER WOMEN’S HEALTHCARE SETTINGS. THE DISCOVERIES GENERATED BY THIS PROJECT WILL ESTABLISH A PREVENTIVE INTERVENTION MODEL THAT CAN BE IMPLEMENTED AT SCALE IN DIVERSE HEALTHCARE AND COMMUNITY SETTINGS AS A LOW-COST, HIGH REACH MEANS OF PREVENTING POSTPARTUM DEPRESSION.

IREECH

SUPPORTING STUDENTS MENTAL HEALTH NEEDS IN HIGH-NEED RURAL SCHOOLS: SCHOOL PSYCHOLOGY INCLUSIVE, RURAL, AND INNOVATIVE TRAINING (SPIRIT)

PRENATAL PATHWAYS FOR POVERTY?S INFLUENCE ON THE BRAINS OF TWO GENERATIONS

MAKING THE BUILDING BLOCKS OF EARLY MATH SCALABLE, ACCESSIBLE, AND VIABLE FOR ALL YOUNG CHILDREN AND THEIR TEACHERS -THIS PROJECT WILL BUILD AN INTERACTIVE AND INTEGRATED CURRICULAR AND PROFESSIONAL DEVELOPMENT TECHNOLOGICAL SYSTEM: THE BUILDING BLOCKS TOOLSET. THE BBTOOLSET IS DESIGNED TO BENEFIT ALL EARLY CHILDHOOD EDUCATORS AND THEIR STUDENTS. YOUNG CHILDREN WILL LEARN FROM ENGAGING, EFFECTIVE DIGITAL EDUCATIONAL GAMES AND FACE-TO-FACE ACTIVITIES. TEACHERS WILL RECEIVE JUST-IN-TIME PROFESSIONAL DEVELOPMENT RELATED TO THEIR STUDENTS' DEVELOPMENT AND GUIDANCE ON CURRICULAR CHOICES AND CULTURALLY SENSITIVE PEDAGOGICAL STRATEGIES. THE APP BUILDS ON THE RESEARCH TEAMS' PRIOR WORK ON THE MATHEMATICAL LEARNING TRAJECTORIES OF YOUNG CHILDREN. LEARNING TRAJECTORIES ARE GROUNDED IN RESEARCH ON CHILDREN'S COGNITION AND CONTAIN THREE INTERRELATED COMPONENTS: A LEARNING GOAL, A DEVELOPMENTAL PROGRESSION OF LEVELS OF THINKING, AND INSTRUCTIONAL ACTIVITIES THAT CORRELATE TO EACH LEVEL. RESEARCH-BASED CURRICULAR RESOURCES AND PROFESSIONAL DEVELOPMENT ARE NOT ALWAYS AVAILABLE TO UNDERSERVED COMMUNITIES, AND THE PANDEMIC HAS ONLY EXACERBATED INEQUITIES BASED ON INCOME AND RACE. THUS, ALL PHASES OF RESEARCH AND DEVELOPMENT OF THE BBTOOLSET WILL BE CONDUCTED COLLABORATIVELY WITH DIVERSE COMMUNITIES. THE PROJECT TEAM WILL ENSURE EQUITABLE MATERIALS AND ACCESS IN THREE WAYS. FIRST, THE RESOURCES EMBEDDED IN THE LEARNING TRAJECTORIES ACTIVITIES WILL INCLUDE EXTENSIVE GUIDES AND JUST-IN-TIME TIPS TO PROMOTE CULTURALLY RESPONSIVE ENACTMENT OF DIGITAL AND FACE-TO-FACE ACTIVITIES. SECOND, TEACHING APPROACHES AND STRATEGIES WILL BE INCLUDED THAT ARE KNOWN TO PROMOTE ENGAGEMENT, LEARNING, AND IDENTIFICATION FOR SPECIFIC MARGINALIZED POPULATIONS, INCLUDING SUPPORT FOR MULTILINGUAL LEARNERS. THIRD, ALL COMPONENTS ARE DESIGNED TO BE ACCESSIBLE USING UNIVERSAL DESIGN FOR LEARNING AND INCORPORATING ADAPTATIONS FOR CHILDREN WITH DISABILITIES. THE RESEARCH TEAM WILL USE THE CURRICULUM RESEARCH FRAMEWORK FROM PRIOR WORK FOR THE DEVELOPMENT AND BOTH FORMATIVE AND SUMMATIVE EVALUATION OF THE BBTOOLSET, PAYING PARTICULAR ATTENTION TO HOW MUCH ITS USE INCREASES ENGAGEMENT AND LEARNING FOR CHILDREN AND TEACHERS. THE WORK WILL ALSO ENSURE THAT ALL CHILDREN, PRIMARILY FROM UNDERSERVED POPULATIONS, BENEFIT FULLY. IN FORMATIVE PHASES, THE RESEARCH AND DEVELOPMENT WILL INCLUDE FOCUS GROUPS, SURVEYS, AND SYSTEM DATA INVOLVING TEACHERS AND CHILDREN. ANALYSES OF DETAILED DATA FROM THOUSANDS OF PARTICIPANTS WILL GUIDE THE ONGOING REFINEMENT OF THE BBTOOLSET SYSTEM AND THE FORMATIVE ASSESSMENT COMPONENTS OF LEARNING TRAJECTORIES. THE DEVELOPMENTAL PROGRESSIONS WILL BE ASSESSED AND REFINED, AS WILL THE INSTRUCTIONAL ACTIVITIES (INCLUDING DIGITAL EDUCATIONAL GAMES). IN SUMMATIVE PHASES, THE PROJECT WILL UTILIZE AN EXPERIMENTAL RESEARCH DESIGN WITHIN CLASSROOMS AND ACROSS THE ENTIRE PROJECT POPULATIONS. DATA WILL BE ANALYZED WITH HIERARCHICAL LINEAR MODELING TO EVALUATE THE EFFICACY AND EFFECTIVENESS OF THE INTERVENTION. THE PROJECT WILL PROVIDE TEACHERS WITH A VALIDATED RESOURCE THAT DOES NOT REQUIRE SUBSTANTIAL INITIAL OR ADDITIONAL WORK. THE EMPIRICAL WORK ALSO WILL VALIDATE FORMATIVE ASSESSMENT AS A POWERFUL ELEMENT OF THE INSTRUCTIONAL PROCESS AND PROVIDE RESEARCHERS WITH EXTENSIVE DATA AND A TOOL THEY COULD USE TO COLLECT NEW DATA. THUS, THE PROJECT WILL CONTRIBUTE TO ADVANCING KNOWLEDGE IN COGNITION, CURRICULUM, AND THE SCALE-UP OF EDUCATIONAL INNOVATIONS THROUGH TECHNOLOGY. THE DISCOVERY RESEARCH PREK-12 PROGRAM (DRK-12) SEEKS TO SIGNIFICANTLY ENHANCE THE LEARNING AND TEACHING OF SCIENCE, TECHNOLOGY, ENGINEERING AND MATHEMATICS (STEM) BY PREK-12 STUDENTS AND TEACHERS, THROUGH RESEARCH AND DEVELOPMENT OF INNOVATIVE RESOURCES, MODELS AND TOOLS. PROJECTS IN THE DRK-12 PROGRAM BUILD ON FUNDAMENTAL RESEARCH IN STEM EDUCATION AND PRIOR RESEARCH AND DEVELOPMENT EFFORTS THAT PROVIDE THEORETICAL AND EMPIRICAL JUSTIFICATION FOR PROPOSED PROJECTS. 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.

GRADUATE PSYCHOLOGY EDUCATION PROGRAMS

PRECLINICAL ELECTRON PARAMAGNETIC RESONANCE TUMOR IMAGER

PRECLINICAL ELECTRON PARAMAGNETIC RESONANCE TUMOR IMAGER - SUMMARY REVOLUTIONARY METHODS OF ACQUIRING ELECTRON PARAMAGNETIC RESONANCE (EPR) SPECTRA OF FREE RADICALS CREATE A PARADIGM SHIFT IN APPLICATION OF EPR TO UNDERSTANDING THE ROLE OF RADICALS IN CANCER AND IN OTHER DISEASES. HITHERTO IMPOSSIBLE STUDIES ARE NOW FEASIBLE. MOLECULAR OXYGEN, PH, LOCAL VISCOSITY, DISTRIBUTION OF PROBES, AND GENERAL REDOX STATUS OF TISSUES ARE CRUCIAL PARAMETERS TO UNDERSTAND TUMORS, DETERMINE TARGETS FOR RADIATION AND CHEMOTHERAPY, AND TO MONITOR RESPONSE TO TREATMENTS. LUNG DAMAGE, STROKE, MYOCARDIAL INFARCTION, BRAIN INJURY, WOUND HEALING, AND OTHER TRAUMA, AND PERIPHERAL VASCULAR LIMITATIONS MAY SIMILARLY BENEFIT FROM EPR IMAGING OF REDOX STATUS. THESE PHYSIOLOGIC PARAMETERS CAN BE MEASURED USING NITROXIDE RADICALS, WHICH ARE OPTIMALLY DETECTED WITH RAPID SCAN EPR. PULSED EPR MEASUREMENT OF LOCAL OXYGEN CONCENTRATION WITH TRITYL RADICALS CAN GUIDE RADIATION TREATMENT OF TUMORS IN MICE. THE PROPOSED SYSTEM WILL INCLUDE BOTH OF THESE POWERFUL TECHNIQUES. EXPERIENCED COLLABORATORS WILL TEST THE IMAGER IN APPLICATIONS TO REDOX EQUILIBRIA IN MOUSE TUMORS, REACTIVE OXYGEN SPECIES RELATED TO CANCER IN MICE, AND ACUTE LUNG INJURY. SPACE IS AT A PREMIUM IN MEDICAL FACILITIES, AND IN INDUSTRY FLOOR SPACE FOR A NEW MODALITY IS EXPENSIVE. LOOKING TOWARD EXPANDED USE IN THE PHARMACEUTICAL INDUSTRY THE 1 GHZ IMAGER WILL BE COMPACT AND TRANSPORTABLE. SMALLER, FASTER, MORE VERSATILE IMAGING WILL ENHANCE APPLICATIONS OF OXIMETRIC IMAGING TO TUMOR THERAPY AND TO THE OTHER PATHOLOGIES LISTED ABOVE. THE PROTOTYPE WITH TECHNOLOGY FOR BOTH RAPID SCAN SPECTROSCOPY AND OXIMETRIC IMAGING WILL OPEN NEW VISTAS FOR QUANTIFYING MORE PHYSIOLOGIC PARAMETERS THAN OXIMETRY ALONE. THE INTEGRATED SOFTWARE SYSTEM WILL ENABLE USE BY TECHNICIANS WITHOUT ADVANCED TRAINING IN THE UNDERLYING SPECTROSCOPY. THE INDUSTRIAL PARTNER, BRUKER BIOSPIN, AND UNIVERSITY OF DENVER’S ENGINEERS WILL DESIGN A NEW GENERATION OF 1 GHZ CROSS-LOOP AND SURFACE COIL RESONATORS, A SMALL MAGNET AND SCAN COILS. BRUKER CONTRIBUTES SUPPLEMENTAL (OPTIONAL) SUPPORT BEYOND THE GRANT BUDGET WITH ENGINEERING TEAM COMMITMENTS TO WORK ON COMMERCIALIZING OUR RAPID SCAN EPR METHOD AND COMPONENTS. BRUKER BRINGS TO THE TEAM ESSENTIAL EXPERIENCE AND KNOW-HOW OF COMMERCIAL STANDARDS, MANUFACTURABILITY, LONG-TERM SUPPORT, AND CUSTOMER NEEDS. LACK OF THE PROPOSED CAPABILITY HAS STYMIED THE EXPANSION OF EPR CAPABILITIES INTO MORE GENERAL BIOMEDICAL RESEARCH USE. THE INNOVATION IS THE CREATION OF A PROTOTYPE THAT OUR TEAM’S INDUSTRIAL COMPONENT CAN REFINE INTO A MARKETABLE PRODUCT WITH POWERFUL EPR CAPABILITY FOR END USERS.

SEXUAL MINORITY COUPLES' HEALTH DURING THE TRANSITION TO MARRIAGE - PROJECT SUMMARY SEXUAL AND GENDER MINORITY (I.E., LESBIAN, GAY, BISEXUAL, QUEER OR OTHER NON-HETEROSEXUAL OR NON-CIS GENDER) ADULTS ARE A POPULATION THAT EXPERIENCES SIGNIFICANT MENTAL AND PHYSICAL HEALTH DISPARITIES. THIS PROJECT ADDRESSES SEXUAL AND GENDER MINORITY HEALTH THROUGH A FOCUS ON THE ROMANTIC RELATIONSHIP CONTEXT OF HEALTH, SPECIFICALLY AT THE POINT OF MARRIAGE. LEGALIZED MARRIAGE IS ONLY NEWLY AVAILABLE TO SEXUAL MINORITY COUPLES IN THE UNITED STATES AS OF 2015, BUT DECADES OF RESEARCH HAVE DEMONSTRATED THAT MARRIAGE HAS HEALTH BENEFITS FOR HETEROSEXUAL COUPLES. SEXUAL AND GENDER MINORITY STRESS IS A PRIMARY DRIVER OF HEALTH DISPARITIES FOR THIS POPULATION AND MARRIAGE MAY BUFFER OR EXACERBATE MINORITY STRESS EXPERIENCES FOR COUPLES. THIS LONGITUDINAL STUDY WILL EXAMINE THE INTERSECTION OF SEXUAL MINORITY STRESS AND MARRIAGE. IT WILL MEASURE HEALTH AT MULTIPLE LEVELS OF ANALYSIS AMONG RECENTLY-MARRIED SEXUAL MINORITY COUPLES, INCLUSIVE OF GENDER IDENTITY, ACROSS THE FIRST TWO YEARS OF MARRIAGE THROUGH THE FOLLOWING AIMS. 1) THROUGH REPEATED QUANTITATIVE SURVEYS WITH SEXUAL MINORITY COUPLES (N=250 COUPLES) OVER THE FIRST TWO YEARS OF MARRIAGE, WE WILL EXAMINE CHANGES IN MINORITY STRESS, RELATIONSHIP PROCESSES, AND PHYSICAL AND MENTAL HEALTH, AS WELL AS RELATIONSHIP MEDIATORS AND MODERATORS OF THE WELL-ESTABLISHED LINK BETWEEN MINORITY STRESS AND HEALTH. 2) THROUGH LONGITUDINAL QUALITATIVE INTERVIEWS (N=24-30 COUPLES ENROLLED FROM AIM 1), WE WILL EXPLORE THE EVOLVING MEANING OF MARRIAGE OVER THE NEWLYWED PERIOD, AS WELL AS PERCEPTIONS OF HOW MARRIAGE SHAPES MINORITY STRESS. 3) USING A SUB-SET OF COUPLES (N=100), WE WILL REPEATEDLY MEASURE PHYSIOLOGICAL MARKERS OF STRESS (CORTISOL, ALPHA AMYLASE) AND ASSOCIATIONS WITH RELATIONSHIP INTERACTIONS AND MINORITY STRESS IN COUPLES’ DAILY LIVES. THIS STUDY WILL MEASURE BOTH SELF- REPORTED HEALTH AND BIOLOGICAL MEDIATORS OF HEALTH AT AN IMPORTANT TRANSITION IN SEXUAL MINORITY COUPLES’ LIVES. THE PROPOSED R01 IS RESPONSIVE TO PAR-21-281 ON DYADIC PROCESSES AND BIOPSYCHOSOCIAL HEALTH, NIH’S TRANS-NIH STRATEGIC PLAN FOR SEXUAL AND GENDER MINORITY HEALTH RESEARCH (NOT-MD-19-001), AND NIMHD’S SCIENTIFIC VISION. OUR PILOT DATA SUGGEST THAT: 1) SEXUAL MINORITY INDIVIDUALS FACE UNIQUE CHALLENGES TO HEALTHY RELATIONSHIP FORMATION, 2) THEY APPEAR TO VIEW MARRIAGE AS A LIFE CHOICE IN A FUNDAMENTALLY UNIQUE WAY, AND 3) MARRIAGE IS A POTENTIALLY CRITICAL CONTEXT FOR UNDERSTANDING SEXUAL MINORITY COUPLES’ MENTAL AND PHYSICAL HEALTH. THE DISCOVERIES GENERATED BY THIS PROJECT WILL MAKE IMPORTANT CONTRIBUTIONS TO AN UNEXPLORED AND CRITICAL LIFE AND RELATIONSHIP TRANSITION: MARRIAGE, WHICH IS UNIQUELY SHAPED BY THE SOCIAL CONTEXT OF SEXUAL ORIENTATION AND HAS CLEAR IMPLICATIONS FOR THE HEALTH OF SEXUAL MINORITY COUPLES.

RAPID SCAN BIOMEDICAL EPR SPECTROSCOPY AND IMAGING

CHILD WELFARE TRAINING

LONG TERM EFFECTS OF PREMARTIAL INTERVENTION

NUCLEIC ACIDS ROLES IN PROTEIN FOLDING AND AGGREGATION - PROJECT SUMMARY THIS PROJECT IS TO INVESTIGATE HOW NUCLEIC ACIDS ARE INVOLVED IN PROTEIN AGGREGATION AND FOLDING. PROTEIN MISFOLDING AND AGGREGATION LEAD TO MANY DEBILITATING DISEASES INCLUDING ALZHEIMER’S DISEASE. WE RECENTLY FOUND THAT NUCLEIC ACIDS CAN HAVE STRONG CHAPERONE ACTIVITY TO PREVENT PROTEIN AGGREGATION AND AID PROTEIN FOLDING. GIVEN THEIR PREPONDERANCE IN THE CELL AND STRONG EFFECTS ON PROTEIN FOLDING AND AGGREGATION, IT IS HIGHLY LIKELY THAT NUCLEIC ACIDS ARE IMPORTANT PLAYERS IN PROTEIN HOMEOSTASIS. THE WORK DESCRIBED IN THIS PROPOSAL LAYS OUT STUDIES TO PROVIDE OUR FIRST UNDERSTANDING OF THE BASIC PRINCIPLES BY WHICH NUCLEIC ACIDS MODULATE PROTEIN FOLDING AND AGGREGATION, AND THUS PROTEIN HOMEOSTASIS. OUR CURRENT INVESTIGATIONS ARE DIRECTED AT ADDRESSING TWO CRITICAL ASPECTS: 1) UNDERSTANDING THE ROLES OF CHAPERONE NUCLEIC ACIDS IN THE CELL, AND 2) UNDERSTANDING THE MOLECULAR MECHANISM OF CHAPERONE NUCLEIC ACIDS. THESE STUDIES UTILIZE AN INTERDISCIPLINARY APPROACH COMBINING MOLECULAR BIOLOGY, BIOCHEMISTRY, BIOPHYSICS, AND BACTERIAL GENETICS. OUR PRELIMINARY DATA INDICATES THAT BOTH THE ACTIVITIES OF NUCLEIC ACIDS TO PREVENT AND PROMOTE OLIGOMERIZATION ARE HIGHLY SEQUENCE DEPENDENT, AND ARE ESPECIALLY ENCODED FOR BY QUADRUPLEX STRUCTURES. THESE RESULTS HELP EXPLAIN THE BIOPHYSICAL CAUSES OF SEVERAL NEURODEGENERATIVE DISEASES. THIS INSIGHT ALSO GIVES US THE OPPORTUNITY TO CONTROL AND STUDY PROTEIN AGGREGATION USING SPECIFIC NUCLEIC ACID SEQUENCES AND STRUCTURES. OUR PRELIMINARY DATA ALSO INDICATES THAT QUADRUPLEX-CONTAINING CHAPERONE SEQUENCES ARE ALSO EFFECTIVE AT IMPROVING THE FOLDING ENVIRONMENT IN E. COLI. WE ARE CURRENTLY EXPANDING THESE STUDIES TO KNOWN QUADRUPLEX STRUCTURES WITH CHAPERONE-LIKE EFFECTS IN THE CELL, AND INVESTIGATING THE STRUCTURAL BASIS OF CHAPERONE ACTIVITY. TOGETHER, THESE STUDIES WILL LAY THE FOUNDATION FOR A NEW UNDERSTANDING OF PROTEIN HOMEOSTASIS AND HOW IT RELATES TO NUCLEIC ACID BIOLOGY. THIS INFORMATION WILL BE CRITICAL IN THE FUTURE TO HELP COMBAT MYRIAD PROTEIN MISFOLDING AND AGGREGATION DISEASES.

CENTER FOR EQUITY AND RESILIENCE IN TRAUMA-RESPONSIVE ORGANIZATIONS - HEALTH DISPARITIES AND SYSTEMIC INEQUITIES CAUSE CHILD TRAUMATIC STRESS TO HAVE A DISPROPORTIONATE IMPACT ON MARGINALIZED COMMUNITIES. ADDRESSING THESE DISPARITIES REQUIRES A DIVERSE, SKILLED, WELL-SUPPORTED, AND RESILIENT WORKFORCE. THE PROPOSED PROJECT, TITLED THE "CENTER FOR EQUITY AND RESILIENCE IN TRAUMA-RESPONSIVE ORGANIZATIONS," WILL CREATE A TREATMENT AND SERVICE ADAPTATION CENTER TO DEVELOP AND IMPLEMENT A COMPREHENSIVE APPROACH TO ADDRESSING THESE ISSUES. SECONDARY TRAUMATIC STRESS IS A MAJOR CONTRIBUTOR TO TURNOVER IN THE HELPING PROFESSIONS, AND IT IMPEDES THE ABILITY OF PROVIDERS TO RESPOND EFFECTIVELY TO THE CHILDREN AND FAMILIES THEY SERVE. A LACK OF DIVERSITY IN THE WORKFORCE CONTRIBUTES TO MENTAL HEALTH DISPARITIES, LACK OF TREATMENT ENGAGEMENT, AND ATTRITION AMONG BLACK, INDIGENOUS, AND PEOPLE OF COLOR. SUPPORTING A DIVERSE WORKFORCE AND PREVENTING AND ADDRESSING SECONDARY TRAUMATIC STRESS ARE UPSTREAM APPROACHES THAT CAN REACH MULTITUDES OF CHILDREN AND FAMILIES BY IMPROVING THE WORKFORCE’S ABILITY TO PROVIDE GOOD CARE. THE CENTER WILL BE A PARTNERSHIP BETWEEN THE UNIVERSITY OF DENVER BUTLER INSTITUTE FOR FAMILIES, AND THE UNIVERSITY OF COLORADO KEMPE CENTER FOR THE PREVENTION AND TREATMENT OF CHILD ABUSE AND NEGLECT. BUTLER AND KEMPE HAVE DEVELOPED AN APPROACH WITH PROMISING INITIAL EVALUATION. WITH THE SUPPORT OF THIS FUNDING OPPORTUNITY, THE CENTER WILL EXPAND, EVALUATE, REFINE, AND DISSEMINATE THIS APPROACH TO BUILD A DIVERSE, SKILLED, WELL-SUPPORTED, AND RESILIENT WORKFORCE AMONG ACROSS CHILD-, YOUTH-, AND FAMILY-SERVING SYSTEMS IN COLORADO AND NATIONWIDE. THE CENTRAL ACTIVITIES FOR THE PROJECT INCLUDE THE DEVELOPMENT, IMPLEMENTATION, AND DISSEMINATION OF THE COMPREHENSIVE APPROACH WHICH WILL STRENGTHEN THE RESILIENCE AND WELL-BEING OF THE WORKFORCE (GOAL #1) AND SUPPORT A DIVERSE WORKFORCE BY ADVANCING EQUITY AND ADDRESSING RACE-BASED TRAUMATIC STRESS IN THE WORKPLACE (GOAL #2). THESE EFFORTS WILL BE COMPLEMENTED BY IMPROVING THE KNOWLEDGE AND SKILLS OF THE WORKFORCE TO CARE FOR CHILDREN AND FAMILIES IMPACTED BY TRAUMA WITH A LENS OF EQUITY (GOAL #3). ADDITIONALLY, THE PROJECT WILL DEVELOP MATERIALS ADDRESSING THE ABOVE OUTCOMES FOR NATIONAL DISSEMINATION IN PARTNERSHIP WITH THE NCTSN (GOAL #4). THE COMPREHENSIVE APPROACH WILL BE EVALUATED USING EQUITABLE EVALUATION PRINCIPLES AND REFINED TO ENSURE EFFECTIVENESS. MEASURABLE OBJECTIVES INCLUDE THE FOLLOWING: 1) AT LEAST 500 PEOPLE COMPLETE THE 16-HOUR STRENGTHENING RESILIENCE TO PREVENT AND ADDRESS STS TRAINING SERIES AND 80% OF THOSE WILL SHOW DECREASES IN RATES OF BURNOUT AND STS; 2) AT LEAST 200 SUPERVISORS IN THE BEHAVIORAL HEALTH, EDUCATION, AND CHILD-, YOUTH-, AND FAMILY-SERVING SYSTEMS COMPLETE TRAUMA-INFORMED SUPERVISION TRAINING; 3) 100 SUPERVISORS AND ADMINISTRATORS AND 200 STAFF COMPLETE THE FROM HISTORICAL TRAUMA TO MODERN OPPRESSION: UNDERSTANDING RACISM, RACE-BASED TRAUMATIC STRESS, AND CULTURAL HEALING MODULE; 4) 20 AGENCIES PARTICIPATE IN A ZOOM-FACILITATED COMMUNITY OF PRACTICE AND COACHING AND 80% OF THOSE AGENCIES WILL SHOW IMPROVEMENTS IN WORKPLACE EQUITY AND INCREASES IN STAFF INTENT TO STAY, PARTICULARLY AMONG BIPOC STAFF; 5) MATERIALS FOR ALL 4 STRENGTHENING RESILIENCE MODULES AND THE HISTORICAL TRAUMA TRAINING ARE TRANSCREATED AND PILOTED WITH NATIVE SPANISH SPEAKERS; AND 6) TWO ASYNCHRONOUS WEB-BASED TRAININGS (ONE IN SPANISH) ARE DEVELOPED.

USING RULE SPACE AND POSET-BASED ADAPTIVE TESTING METHODOLOGIES TO IDENTIFY ABILITY PATTERNS IN EARLY MATHEMATICS AND CREATE A COMPREHENSIVE MATHEMAT

OPERATION OF THE NLECTC - ROCKY MOUNTAIN FY09 AND SUPPORT OF WEAPONS AND PROTECTIVE SYSTEMS CENTER OF EXCELLENCE

A MICROSOCIAL VIDEO-COACHING INTERVENTION FOR TOXICALLY STRESSED EHS FAMILIES

INTEGRATED, INTELLIGENT AND INTERACTIVE TECHNOLOGIES BUILDING YOUNG CHILDREN’S MATH ALONG LEARNING TRAJECTORIES

EARLY CHILDHOOD EDUCATION IN THE CONTEXT OF MATHEMATICS, SCIENCE, AND LITERACY

CO RELEASING ORGANIC POLYMERS FOR BIOMEDICAL APPLICATIONS - PROJECT SUMMARY/ABSTRACT OVER THE LAST SEVERAL DECADES IT HAS BECOME APPARENT THAT CARBON MONOXIDE (CO) GAS IS AN IMPORTANT SMALL MOLECULE THAT GREATLY IMPACTS HUMAN HEALTH. INDEED, CO IS CREATED ENDOGENOUSLY IN SMALL CONCENTRATIONS AND HAS BEEN SHOWN TO BE AN ESSENTIAL SIGNALING MOLECULE IN THE HUMAN NEURONAL SYSTEM. MOREOVER, CO GAS HAS BEEN REVEALED TO BE A VALUABLE THERAPEUTIC, SPECIFICALLY, IT CAN AMELIORATE ACUTE AND CHRONIC INFLAMMATION, CAN REDUCE REJECTION OF ORGAN TRANSPLANTS, AND CAN TREAT CARDIOVASCULAR DISEASES. HOWEVER, THE DIRECT STUDY OR USE OF CO IN BIOLOGICAL SYSTEMS IS INHERENTLY COMPLEX BECAUSE IT IS A GAS, HAS LIMITED SOLUBILITY IN WATER, AND IS TOXIC AT HIGH CONCENTRATIONS. AS SUCH, MANY OF THE MECHANISMS AND PATHWAYS BY WHICH CO OPERATES IN THE HUMAN BODY REMAIN ELUSIVE. IN RESPONSE TO THESE COMPLICATIONS, CO RELEASING MOLECULES (CORMS) HAVE EMERGED AS A CLASS OF MATERIALS THAT CAN RELEASE CO IN RESPONSE TO AN EXTERNAL STIMULUS. AS TRANSITION METALS READILY LIGATE TO AND RELEASE CO UNDER VARIOUS CONDITIONS, THESE MATERIALS WERE THE FIRST CLASS OF CORMS DEVELOPED AND REMAIN THE MOST POPULAR AND FREQUENTLY UTILIZED TO DATE. UNFORTUNATELY, CORMS BASED ON TRANSITION METAL CARBONYL COMPLEXES ARE CYTOTOXIC, FORM POORLY DEFINED PRODUCTS FOLLOWING RELEASE OF CO, AND CANNOT BE DIRECTLY POLYMERIZED TO FORM MACROMOLECULAR TARGETED THERAPEUTICS. RESEARCH IN THE WORRELL LABORATORY IS INSPIRED BY THE SHORTCOMINGS IN CURRENT CORM TECHNOLOGY, AND WE ARE ACTIVELY ENGAGED IN CREATING STABLE, MODULAR, AND EFFICIENT ORGANIC CO RELEASING MOLECULES. OUR WORK HAS BEEN CONCENTRATED ON ANALOGS OF DIPHENYLCYCLOPROPENONE (DPCP), A UNIQUELY STABLE AND BIO-ORTHOGONAL MOLECULE THAT FEATURES A HIGHLY STRAINED 3 MEMBERED RING. PREVIOUS WORK IN A SMALL MOLECULE SETTING HAS SHOWN THAT DPCP IS UNRIVALED IN ITS ABILITY TO CLEANLY AND EFFICIENTLY PRODUCE CO GAS. PROOF-OF-CONCEPT DEMONSTRATIONS HAVE SHOWN THAT ANALOGS OF DPCP CAN BE EFFECTIVELY SYNTHESIZED, CAN BE DIRECTLY POLYMERIZED, AND CAN RELEASE CO GAS BY PHOTOLYSIS, HOWEVER, FOR APPLICATION AS A CORM, THIS MUST BE DEMONSTRATED IN A BIOLOGICAL SYSTEM. FUTURE WORK OVER THE FIVE-YEAR COURSE OF THIS PROGRAM WILL CONCENTRATE ON THE DEVELOPMENT OF METHODS FOR THE CONTROLLED POLYMERIZATION OF DPCP TO CREATE TAILORED MACROMOLECULAR MATERIALS THAT ARE SOLUBLE, TARGETED, NON-TOXIC, AND BIOCOMPATIBLE. WE WILL FURTHER CONCENTRATE ON IMPROVING THE RATE AND EFFICACY OF CO RELEASE BY LEVERAGING THE UNIQUE PHOTOPHYSICS OF DPCPS WHILE CREATING WELL-DEFINED PHOTOPRODUCTS. ULTIMATELY, THE MOST IMPACTFUL EXTENSION OF THIS WORK WILL BE RELATED TO ITS DEVELOPMENT IN STUDYING AND TREATING GASTROINTESTINAL INFLAMMATION AS PART OF A LONG-TERM COLLABORATION WITH THE COLGAN/ONYIAH GROUP AT THE UNIVERSITY OF COLORADO MEDICAL SCHOOL. ALTHOUGH THERE ARE SIGNIFICANT CHALLENGES ASSOCIATED WITH THIS PROGRAM, ITS SCIENTIFIC IMPACTS WILL BE FAR-REACHING. IF SUCCESSFUL, ORGANIC CORMS WILL SUPERSEDE THOSE BASED ON TRANSITION METAL COMPLEXES, STIMULATING THE DEVELOPMENT OF NEW TARGETED THERAPEUTICS BASED ON THE PRODUCTION OF CO GAS.

A LOWER EXTREMITY NEUROMUSCULOSKELETAL HUMAN SIMULATOR: ADDRESSING MULTISCALE CHALLENGES

NATIONAL CENTER FOR EDUCATION RESEARCH

BEHAVIORAL HEALTH WORKFORCE EDUCATION AND TRAINING PROGRAM- AMERICAN RESCUE PLAN

TAKING DEVELOPMENT (IM)BALANCE SERIOUSLY: USING NEW APPROACHES TO MEASURE AND MODEL STATE FRAGILITY

NORADRENERGIC DYSFUNCTION IN DOWN SYNDROME

POLARIZED PROTEIN TRAFFICKING AND ANGIOGENESIS - SUMMARY BLOOD VESSELS CARRY OXYGEN AND NUTRIENTS AND ARE VITAL TO ORGANISMIC VIABILITY AND CONTINUED HOMEOSTASIS. ANGIOGENESIS, OR THE FORMATION OF NEW BLOOD VESSELS FROM PRE-EXISTING ONES, IS THE PREDOMINANT DEVELOPMENTAL PROCESS BY WHICH BLOOD VESSEL NETWORK DENSITY IS REGULATED. DURING ANGIOGENIC DEVELOPMENT, ENDOTHELIAL CELLS CREATE A HOLLOW CAVITY CALLED A LUMEN, PROVIDING A CONTINUOUS CONDUIT FOR BLOOD TO REACH DISTANT TISSUES. THE MECHANISMS UNDERPINNING THE MORPHODYNAMIC CHANGES IN ENDOTHELIAL ARCHITECTURE AND SIGNALING LEADING TO VASCULAR LUMEN FORMATION, OR TUBULOGENESIS, ARE INCOMPLETELY UNDERSTOOD. IN THIS PROPOSAL WE WILL INVESTIGATE A PROTEIN CALLED SYNAPTOTAGMIN-LIKE PROTEIN 2 (SYTL2) THAT WE BELIEVE IS RESPONSIBLE FOR DENING THE LUMINAL SURFACE BY DIRECTING PROTEIN TRANSPORT TO THE APICAL MEMBRANE DURING BLOOD VESSEL DEVELOPMENT. OUR PRELIMINARY DATA SUGGESTS THAT SYTL2 DENES THE APICAL MEMBRANE AND TETHERS RAB GTPASE PROTEINS FOR DELIVERY OF VESICULAR CARGO, SUCH AS PODOCALYXIN. IN AIM 1, WE WILL CHARACTERIZE THE ROLE OF SYTL2A DURING VASCULAR LUMEN FORMATION IN DEVELOPING ZEBRASH EMBRYOS USING A COMBINATION OF LIVE-IMAGING AND CRISPR-BASED MUTANT GENERATION. IN AIM 2, WE WILL COMPREHENSIVELY DEMONSTRATE THAT SYLT2 WORKS IN COMBINATION WITH THE GTPASE RAB35 TO DELIVER PODOCALYXIN TO THE APICAL PLASMA MEMBRANE DURING LUMENOGENESIS IN VITRO. IN AIM 3, WE WILL FURTHER CHARACTERIZED HOW SYTL2A INTERACTS WITH RAB35 TO DELIVER PODOCALYXIN USING GENERATION OF NEW ZEBRASH REPORTER LINES AND COMPOUND MUTANTS IN VIVO. HOW BLOOD VESSEL LUMEN FORMATION IS REGULATED IS STILL A MAJOR QUESTION IN THE ELD, THIS PROPOSAL WILL PROVIDE NOVEL INSIGHT INTO CRITICAL MECHANISMS ORCHESTRATING THIS PROCESS.

PHYSIOLOGICAL PLASTICITY AND THE MECHANISMS OF ADAPTATION TO HYPOXIA: EXPLOITING NATURAL VARIATION IN WILD DEER MICE - PROJECT SUMMARY THE MAINTENANCE OF O2 HOMEOSTASIS IS A CRITICAL COMPONENT OF HUMAN HEALTH. ITS DISRUPTION, FOR EXAMPLE, CONTRIBUTES TO THE PATHOPHYSIOLOGY OF MANY DEVASTATING DISEASES, INCLUDING HEART, LUNG, AND CEREBROVASCULAR DISEASE. IN ADDITION, PERVASIVE REDUCTIONS IN ENVIRONMENTAL O2 AVAILABILITY AT HIGH ALTITUDES POSE A SERIOUS THREAT TO THE GROWING NUMBER OF PEOPLE WORLDWIDE THAT LIVE ABOVE 2500 METERS. FOR EXAMPLE, LONG-TERM EXPOSURE TO HIGH ALTITUDE HYPOXIA CAN LEAD TO CHRONIC CONDITIONS SUCH AS CHRONIC MOUNTAIN SICKNESS, AS WELL AS NEGATIVE PREGNANCY OUTCOMES, HEART FAILURE OR EVEN DEATH. THIS IS BECAUSE UNDER CONDITIONS OF CHRONIC ENVIRONMENTAL HYPOXIA, SEVERAL PHYSIOLOGICAL RESPONSES AIMED AT MAINTAINING HOMEOSTASIS UNDER ACUTE HYPOXIC CONDITIONS CAN LEAD TO MALADAPTIVE REMODELING OF THE PULMONARY VASCULATURE AND INCREASES IN BLOOD VISCOSITY THAT CAN OVERBURDEN THE HEART. IN THE VELOTTA LAB, WE STUDY WILD, HIGH-ALTITUDE DEER MICE (PEROMYSCUS MANICULATUS) AS A MODEL TO UNDERSTAND THE INTEGRATED EVOLUTIONARY MECHANISMS THAT ALLOW ANIMALS TO OVERCOME THESE CHALLENGES. DEER MICE ARE A WELL-SUITED MODEL: THEY ARE BROADLY DISTRIBUTED ACROSS > 4000 METERS OF ELEVATION IN NORTH AMERICA, ARE EASILY CAPTURED IN THE WILD AND MANIPULATED IN THE LAB, ARE RICH IN PHYSIOLOGICAL AND GENOMIC RESOURCES, AND MOST IMPORTANTLY, HAVE ADAPTED OVER EVOLUTIONARY TIME TO THE EXTREME CONDITIONS OF HIGH ALTITUDE. OVER THE NEXT FIVE YEARS, MY LAB WILL DISSECT THE GENETIC AND MOLECULAR MECHANISMS BY WHICH NATURAL SELECTION HAS RESHAPED DEER MOUSE PHYSIOLOGY AT HIGH ALTITUDE. WE WILL USE QUANTITATIVE GENETICS TO IDENTIFY, FOR THE FIRST TIME, THE LOCI THAT UNDERLIE ADAPTIVE VARIATION IN PHYSIOLOGICAL RESPONSE TO HYPOXIA, COUPLED WITH DETAILED RNA- SEQUENCING AND NETWORK-BASED TRANSCRIPTOMIC APPROACHES TO IDENTIFY THE REGULATORY PATHWAYS THAT UNDERLIE SUCH RESPONSES. COMBINING THESE APPROACHES ALLOWS US TO PINPOINT THE GENETIC ARCHITECTURE OF EVOLVED PHYSIOLOGICAL CHANGE AT HIGH ALTITUDE. FINALLY, WE WILL USE OUR UNDERSTANDING OF UNDERLYING GENETIC ARCHITECTURE TO DIRECTLY TEST FOR THE FORM, DIRECTION, AND STRENGTH OF NATURAL SELECTION ON PHYSIOLOGICAL TRAITS DURING ADAPTATION TO THESE EXTREME CONDITIONS. THE LARGE-SCALE AND AMBITIOUS SERIES OF EXPERIMENTS OUTLINED IN THIS PROPOSAL WILL YIELD NEW INSIGHTS INTO HIGH-ALTITUDE BIOLOGY AND MEDICINE AND MAY LEAD TO NOVEL THERAPEUTIC TARGETS FOR DISEASES IN WHICH THE DISRUPTION OF O2 HOMEOSTASIS IS CENTRAL TO THEIR PATHOLOGY.

CNH-L: THE POTENTIAL FOR AQUACULTURE IN LAKE VICTORIA AND IMPLICATIONS FOR WILD FISHERIES AND FISH COMMODITY MARKETS

ORGANOMETALLIC SENSORS FOR CELLULAR SMALL MOLECULE DETECTION - 7. PROJECT SUMMARY/ABSTRACT THE ADAPTATION OF ABIOTIC TRANSITION METAL CATALYSTS FOR APPLICATIONS IN BIOLOGICAL SYSTEMS HAS UNDERGONE REMARKABLE GROWTH IN RECENT YEARS WITH EXAMPLES RANGING FROM ARTIFICIAL METALLOENZYMES TO MOLECULAR PROBES FOR DETECTION OF CHALLENGING ANALYTES SUCH AS CARBON MONOXIDE. THE PI HAS A STANDING INTEREST IN DISCOVERY, DEVELOPMENT, AND UNDERSTANDING OF STRATEGIES FOR DETECTING CHALLENGING BIOLOGICALLY RELEVANT MOLECULES VIA THE UNIQUE REACTIVITY OF TRANSITION METALS. MOST RECENTLY, THE MICHEL GROUP REPORTED BODIPY ETHYLENE PROBES (BEPS) AS THE FIRST PROFLUORESCENT ACTIVITY BASED SENSORS (ABS) FOR THE DETECTION OF ETHYLENE IN BIOLOGICAL SYSTEMS. THESE ABS ADAPTED WELL-KNOWN RUTHENIUM OLEFIN METATHESIS CATALYST, WHICH ARE KNOWN TO READILY REACT WITH ETHYLENE. WHILE ETHYLENE HAS LONG BEEN KNOWN AS AN IMPORTANT PLANT HORMONE IT HAS ALSO BEEN DEMONSTRATED TO BE PRODUCED IN MAMMALS AS A RESULT OF OXIDATIVE STRESS THAT IS HALLMARK TO NUMEROUS DISEASES. IN PARTICULAR ETHYLENE ARISES FROM THE RADICAL FRAGMENTATION OF LIPID PEROXIDES AND/OR INTERMEDIATES IN THEIR FORMATION. THE FORMATION OF LIPID PEROXIDES IS A RESULT OF REACTIVE OXYGEN SPECIES, WHICH ARE IMPLICATED AS PLAYING STRESS OR SIGNALING ROLES IN NUMEROUS DISEASES INCLUDING CANCER, CARDIOVASCULAR DISEASE, AND NEURODEGENERATIVE DISEASES AMONGST OTHERS. WHILE THERE ARE SOME SOPHISTICATED SPECTROSCOPIC METHODS FOR SENSITIVELY MEASURING THE BIOMARKER ETHYLENE IN EXHALED BREATH, THESE APPROACHES ARE NECESSARILY LIMITED IN SPATIAL RESOLUTION AND COMPLEXITY OF SAMPLE. SINCE REPORTING OUR INITIAL ABS APPROACH, OUR GROUP HAS CONDUCTED SYSTEMATIC LIGAND MODULATION STUDIES TO IMPROVE PROBE RESPONSE TIME AND SENSITIVITY. THROUGH THIS WORK THE LIMIT-OF-DETECTION WAS IMPROVED NEARLY TWO ORDERS OF MAGNITUDE. DESPITE THESE ADVANCEMENTS, IMPORTANT QUESTIONS REMAIN FOR BROAD APPLICATIONS IN THE DETECTION OF ENDOGENOUS ETHYLENE RELATED TO MODIFICATIONS THAT FURTHER IMPROVE SENSITIVITY WHILE RETAINING ROBUST STABILITY IN BIOLOGICAL SYSTEMS. THE NEXT STAGE OF DEVELOPING THIS TECHNOLOGY WILL BUILD ON MECHANISTIC INSIGHT AND RECENT ADVANCEMENTS IN CATALYTIC OLEFIN METATHESIS. THIS WILL BE ACCOMPLISHED THROUGH AN INTERDISCIPLINARY APPROACH OF SYNTHESIS, ANALYTICAL AND PHOTOPHYSICAL CHARACTERIZATION, AND SUBCELLULAR LOCALIZATION STUDIES. IT IS ANTICIPATED THAT THE PROPOSED RESEARCH WILL RESULT IN HIGHLY SENSITIVE ETHYLENE ABS LOCALIZED TO SUBCELLULAR LOCATIONS WHERE ETHYLENE IS EXPECTED TO BE FOUND IN THE HIGHEST CONCENTRATIONS. FURTHER WE EXPECT TO EXPLORE NOVEL STRATEGIES FOR ETHYLENE DETECTION BEYOND THE DOSIMETRIC RESPONSES GENERALLY EMPLOYED FOR ETHYLENE AND OTHER SMALL MOLECULE ANALYTES. AS HAS BEEN THE CASE OVER THE PAST 10-15 YEARS, WE ENVISION THAT THERE WILL BE CONTINUED GROWTH OF TRANSITION METAL CATALYSTS OPERATING IN CELLULAR ENVIRONMENTS TO PERFORM CRITICAL FUNCTIONS THAT WOULD OTHERWISE NOT BE POSSIBLE. THE RESEARCH AND CONCEPTS OF THE PROPOSED PROGRAM WILL CONTINUE TO SIGNIFICANTLY CONTRIBUTE TO THIS FIELD. 1

FUNCTIONAL MORPHOLOGY OF TASTE BUDS

COLLABORATIVE RESEARCH: ROL: THE EVOLUTION AND MAINTENANCE OF VARIABLE SPECIES BOUNDARIES

MRI COLLABORATIVE: DEVELOPMENT OF AN INTELLIGENT, AUTONOMOUS, UNMANNED, MOBILE SENSOR

ELUCIDATING THE BIOSYNTHESIS OF MYCOFACTOCIN, AN UNKNOWN MOLECULE ESSENTIAL FOR M. TUBERCULOSIS

REGULATIONS OF ORGANELLAR ZN2+ HOMEOSTASIS AND DYNAMICS BY TRPML1 IN NEURONS

DISES: INDIGENOUS FOREST MANAGEMENT IN A NON-STATIONARY CLIMATE -FORESTS HAVE PROVIDED SHELTER, SUSTAIN, AND PROVIDE ECOSYSTEM GOODS AND SERVICES, INCLUDING CARBON SEQUESTRATION, NOURISHMENT, AND WATER RESOURCES FOR HUMAN SOCIETIES FOR MILLENNIA. FORESTS REFLECT A COMPLEX MIX OF HUMAN MANAGEMENT, EXTRACTION, AND CONSERVATION INTERACTIONS, AND THEY FACE A MYRIAD OF THREATS FROM BOTH ECONOMIC FORCES AND GLOBAL ENVIRONMENTAL CHANGE. THIS AWARD WILL EXPLORE HOW FORESTS HAVE BEEN MANAGED AND SUSTAINED OVER MILLENNIA THROUGH EXPLORING THE HUMAN KNOWLEDGE OF THESE INTERACTIONS. THIS AWARD WILL EXPLORE THE FOREST?S DYNAMICS USING: FORMAL TECHNICAL OR ?WESTERN? SCIENTIFIC AND INDIGENOUS KNOWLEDGE (DEFINED HERE BY LOCAL ANCESTRAL KNOWLEDGE HELD BY INDIGENOUS COMMUNITIES) APPROACHES AND UNDERSTANDING. THIS STUDY WILL RIGOROUSLY ASSESS FOREST DISTURBANCE HISTORY AND MODEL FOREST CLIMATE SENSITIVITY IN NEOTROPICAL CONIFER FORESTS USING WESTERN METHODS FROM TREE-RING STUDIES AND UNDERSTANDING HOW CLIMATIC RISKS ARE PERCEIVED BY INDIGENOUS FOREST MANAGERS, THE FOREST MANAGEMENT SYSTEMS IN PLACE LED BY INDIGENOUS COMMUNITIES, TO UNDERSTAND HOW INDIGENOUS KNOWLEDGE IS APPLIED TO FOREST MANAGEMENT IN THESE COMMUNITIES AND HOW THIS KNOWLEDGE ACQUISITION AND TRANSMISSION COULD BE MODIFIED BY SOCIAL CHANGES INCLUDING MIGRATION, AND HOW THIS RELATES TO THE EXISTING BODY OF INDIGENOUS KNOWLEDGE. THE PROJECT INCLUDES A RANGE OF BROADER IMPACTS RELATED TO EDUCATION, TRAINING, AND CO-PRODUCTION OF KNOWLEDGE FOCUSED ON BUILDING LOCAL CAPACITY AND GENERATING INFORMATION THAT CAN BE APPLIED TO STUDY THE RANGE OF VARIABILITY IN THE COUPLED SOCIO-ENVIRONMENTAL SYSTEM OF FORESTS CONSERVED BY INDIGENOUS COMMUNITIES. FOREST ECOSYSTEMS ARE A CRITICAL COMPONENT OF THE BIOSPHERE AND PLAY AN IMPORTANT ROLE IN COUPLING THE ATMOSPHERE TO THE LAND SURFACE AND CARBON CYCLE. THESE ENVIRONMENTS ALSO SHELTER, SUSTAIN, AND PROVIDE ECOSYSTEM GOODS AND SERVICES, INCLUDING CARBON SEQUESTRATION AND WATER RESOURCES, FOR HUMAN SOCIETIES AT SCALES FROM LOCAL TO GLOBAL. FORESTS ARE FULLY INTEGRATED SOCIO-ENVIRONMENTAL SYSTEMS THAT REFLECT RECIPROCAL INTERACTIONS, EXCHANGES, AND FEEDBACKS BETWEEN BIOSPHERE, ATMOSPHERE, AND HUMAN SOCIETY. TERRESTRIAL PROTECTED AREAS AND ECOLOGICALLY INTACT LANDSCAPES ARE CONSERVED AND MANAGED BY INDIGENOUS PEOPLES, BUT IMMINENT CLIMATE DISRUPTION AND CHANGES IN FOREST DISTURBANCE REGIMES THREATEN THE STATE OF ECOSYSTEMS AND THE HUMAN LIVELIHOODS THAT BOTH DEPEND ON AND AFFECT THEM. INDIGENOUS KNOWLEDGE REFLECTS HOLISTIC ACCUMULATED UNDERSTANDING OF THE SYSTEM BY INDIGENOUS COMMUNITIES; HOWEVER, MIGRATION AND OTHER SOCIAL AND CULTURAL CHANGES HAVE ALTERED THE MODES OF TRANSMISSION OF ENVIRONMENTAL KNOWLEDGE IN THESE COMMUNITIES. HOW DOES MODERN INDIGENOUS KNOWLEDGE INTEGRATE CENTURIES OF SOCIO-ENVIRONMENTAL INTERACTIONS AND EXPERIENCES AND HOW WILL THAT KNOWLEDGE SYSTEM CHANGE IN THE FACE OF SOCIAL AND ENVIRONMENTAL SYSTEMS THAT WILL IMMINENTLY SHIFT BEYOND THE VARIABILITY OF THE LAST SEVERAL CENTURIES? THIS RESEARCH APPROACH COMBINES A LONG-TERM UNDERSTANDING OF PAST, PRESENT, AND FUTURE FOREST HISTORY AND DISTURBANCE FROM DENDROCHRONOLOGY, NOVEL INSIGHTS INTO INDIGENOUS MANAGEMENT AND CONSERVATION PRACTICES THROUGH TIME, AN UNDERSTANDING OF TRADITIONAL ENVIRONMENTAL KNOWLEDGE DYNAMICS, SCALE, AND CHANGE, AND FORECASTS OF FUTURE SOCIO-ECOLOGICAL CHANGE. THIS PROJECT SEEKS TO UNDERSTAND HOW INDIGENOUS KNOWLEDGE OF FOREST DYNAMICS REFLECT CENTURIES OF ECOSYSTEM VARIABILITY AND HOW NON-STATIONARITY IN BOTH THE HUMAN AND ECOLOGICAL COMPONENTS OF THIS COUPLED SYSTEM WILL AFFECT MANAGEMENT, CONSERVATION, AND PRESERVATION OF THIS SOCIO-ECOLOGICAL SYSTEM. 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.

NATIONAL CENTER FOR EDUCATION RESEARCH

CHILDREN EXPOSED TO INTIMATE PARTNER VIOLENCE: MENTAL HEALTH CORRELATES OF CONCOM

THE ROLE OF COHABITATION IN MARRIAGE AND UNION FORMATION

FORMATION OF THE REGULATED SECRETORY PATHWAY: A VIEW FROM THE CYTOSOL

DYNAMICS OF EPITHELIAL POLARITY PROTEINS AND THE CONTROL OF TISSUE ARCHITECTURE

EQUIPMENT: MRI: TRACK 1 ACQUISITION OF A 600 MHZ NMR WITH CRYOPROBE FOR THE GREATER ROCKY MOUNTAIN REGION -AN AWARD IS MADE TO THE UNIVERSITY OF DENVER TO ACQUIRE A STATE-OF-THE-ART 600 MHZ NUCLEAR MAGNETIC RESONANCE (NMR) SPECTROMETER WITH A CRYOPROBE AND A COOLED SAMPLECASE. THIS INSTRUMENT WILL SUPPORT RESEARCHERS AT THE UNIVERSITY OF DENVER AND ACROSS THE GREATER ROCKY MOUNTAIN REGION, ENABLING NEW RESEARCH RANGING FROM UNDERSTANDING BIOMOLECULAR INTERACTIONS TO CHARACTERIZING FUNCTIONAL TOOLS IN COMPLEX BIOLOGICAL SYSTEMS. THIS PROJECT WILL SUPPORT MODERNIZATION OF CURRICULAR ACTIVITIES IN UNDERGRADUATE (ORGANIC LAB SEQUENCE, INSTRUMENTAL ANALYSIS, AND FRONTIERS IN CHEMISTRY) AND GRADUATE COURSES (ORGANIC SPECTROSCOPY AND BIOPHYSICAL METHODS), GREATLY INCREASING THE NUMBER OF STUDENTS EXPOSED MODERN 2D AND MULTINUCLEAR NMR EXPERIMENTS. HIGH-SCHOOL, UNDERGRADUATE, GRADUATE, AND POSTDOCTORAL RESEARCHERS WILL BENEFIT FROM TRAINING ON STATE-OF-THE-ART EQUIPMENT. THIS INCLUDES STUDENTS IN THE SHINE@DU PROGRAM, WHICH PROVIDES PAID 8-WEEK SUMMER INTERNSHIPS TO LOCAL JUNIOR AND SENIOR HIGH-SCHOOL STUDENTS LARGELY FROM GROUPS UNDERREPRESENTED IN THE SCIENCES. THIS PROJECT WILL BENEFIT THE CITIZEN SCIENCE FOLDIT GAME, WHICH WILL CONTINUE TO IMPROVE VIA VALIDATION OF SOLVED STRUCTURES. RESPONSIBLE STEWARDSHIP AND CONSERVATION OF FINITE HELIUM RESOURCES WILL CONTINUE THROUGH HELIUM RECOVERY AND RECYCLING AT THE UNIVERSITY OF DENVER. THE NEW INSTRUMENT WILL ENABLE BIOMOLECULAR AND CHEMICAL RESEARCH OWING TO INCREASED SENSITIVITY, RESOLUTION, TRANSCEIVER CAPABILITY, AND ACCESS THAT IS NOT CURRENTLY POSSIBLE AT THE UNIVERSITY OF DENVER AND IS SEVERELY LIMITED IN THE REGION. THIS NMR WILL ENABLE BIOMOLECULAR RESEARCHERS TO (1) UNDERSTAND HOW NUCLEIC ACIDS INTERACT WITH PROTEINS TO INHIBIT AGGREGATION, (2) INVESTIGATE THE MECHANISM OF HOW SYNTHETIC PROTEIN MIMICS MODULATE ABERRANT PROTEIN-PROTEIN INTERACTIONS, AND (3) DISCOVER AND CHARACTERIZE NOVEL METALLOPHORES. CHEMICAL BIOLOGY AND CHEMICAL RESEARCHERS WILL USE THE NEW NMR SPECTROMETER TO: (1) ELUCIDATE THE STRUCTURES OF COMPLEX POLYHETEROCYCLES, (2) CHARACTERIZE AND INVESTIGATE ORGANOMETALLIC COMPLEXES AS TOOLS FOR PROBING BIOLOGICAL SYSTEMS, AND (3) IDENTIFY AND ANALYZE END-GROUPS OF FUNCTIONAL LINEAR POLYMERS. A NUMBER OF REGIONAL USERS, INCLUDING RESEARCHERS AT PRIMARILY UNDERGRADUATE INSTITUTIONS AND AREA START-UP COMPANIES, WILL HAVE REMOTE AND IN-PERSON ACCESS TO THE NEW NMR. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

HIGH-FAT DIETS AND MEMORY LOSS WITH AGING

SYNTHETIC PROTEIN MIMETICS AS POTENTIAL THERAPEUTICS FOR LEWY BODY DEMENTIA - CURRENTLY, MORE THAN 55 MILLION PEOPLE HAVE DEMENTIA WORLDWIDE AND LEWY BODY DEMENTIA (LBD) MAKES UP TO 30% OF ALL DEMENTIA CASES. THERE ARE NO THERAPIES TO CURE OR SLOW DOWN/STOP THE PROGRESSION OF LBD, MAKING IT A PRESSING NEED TO DEVELOP THERAPEUTICS FOR LBD. THE MAIN CAUSAL AGENT IN LBD IS THE AGGREGATION OF ALPHALPHA-SYNUCLEIN (ΑS) PROTEIN, A NEURONAL PROTEIN THAT IS EXPRESSED IN NEURONS. THE PATHOLOGICAL EVENTS IN LBD INCLUDE ΑS AGGREGATION AND THE SPREAD OF PATHOGENIC ΑS AGGREGATION VIA PRION-LIKE SPREAD THAT IMPAIRS NEURON FUNCTIONS, WHICH LEADS TO LBD PHENOTYPES (COGNITIVE AND MOTOR DEFICITS). THEREFORE, MODULATION OF AGGREGATION AND THE PRION-LIKE SPREAD OF ΑS COULD BE CONSIDERED A PROMISING THERAPEUTIC INTERVENTION FOR LBD. OUR LAB HAS SYNTHESIZED A LARGE LIBRARY OF OLIGOPYRIDYLAMIDES (OPS) BASED SYNTHETIC PROTEIN MIMETICS WITH A LARGE CHEMICAL DIVERSITY. THE OPS MIMIC THE TOPOGRAPHY AND SIDE CHAINS OF PROTEINS, SUCH AS THOSE PRESENT AT PROTEIN AGGREGATION SURFACES. WE HAVE IDENTIFIED POTENT OPS THAT CAN POTENTLY INHIBIT ΑS AGGREGATION AND LB FORMATION IN CELLULAR, NEURONAL, AND C. ELEGANS MODELS. THE OP SPECIFICALLY INTERACTS WITH PATHOLOGICAL ΑS OLIGOMERS WITHOUT DISPLAYING ANY AFFINITY TO PHYSIOLOGICAL ΑS MONOMERS. THE OP EFFICIENTLY CROSSES THE BLOOD BRAIN BARRIER AND INHIBITS LB FORMATION OF LBS IN A MOUSE MODEL WITHOUT DISPLAYING APPARENT TOXICITY. OUR PROPOSED WORK IS DIVIDED INTO TWO PARTS (1) OPTIMIZATION AND TESTING OF THE PHARMACEUTICAL PROPERTIES OF THE OPS, (2) TESTING OF OPS TO RESCUE LBD PHENOTYPES IN A MOUSE MODEL. THE OPS WILL BE TESTED FOR THEIR ADMET PROPERTIES IN HUMAN IN VITRO MODELS. ADDITIONALLY, BASED ON THE CHEMICAL STRUCTURES OF OPS, WE WILL DESIGN AND SYNTHESIZE OPS TO TEST AND OPTIMIZE THE ADMET PROPERTIES IN HUMAN IN VITRO MODEL SYSTEMS. IN TANDEM, THE ANTAGONIST ACTIVITY OF THE OPS WILL BE TESTED AGAINST ΑS AGGREGATION IN VARIOUS MODELS. THIS STUDY WILL ALLOW THE OPTIMIZATION OF THE PHARMACEUTICAL PROPERTIES OF OPS WITHOUT SACRIFICING THEIR ANTAGONIST ACTIVITY AGAINST PATHOLOGICAL LBS. SUBSEQUENTLY, THE OP WILL BE TESTED FOR THEIR ABILITY TO INHIBIT THE LBS IN A MOUSE MODEL. ALSO, THEY WILL BE TESTED TO RESCUE THE LBD PHENOTYPES IN A MOUSE MODEL, INCLUDING THE COGNITIVE AND MOTOR IMPAIRMENTS. THE OPS WILL ALSO BE TESTED FOR THEIR INHERENT TOXICITY IN THE MOUSE MODEL VIA METABOLIC PROFILING, WHERE THE TOXICITY OF THE POTENTIAL METABOLITES OF OPS WILL BE CHARACTERIZED. OVERALL, OUR STUDY WILL IDENTIFY POTENT LEAD THERAPEUTICS FOR LBD WITH OPTIMAL PHARMACEUTICAL AND EFFICACY TO RESCUE LBD PHENOTYPES IN THE MOUSE MODEL. IN THE NEAR FUTURE, WE EXPECT THAT THE OPS WILL BE READY TO BE TESTED FOR PHARMACOLOGY, PHARMACOKINETICS, AND TOXICOLOGY ASSESSMENTS IN THE ANIMAL MODELS TO FURTHER ADVANCE THEM IN THE CLINICAL TRIALS FOR LBD.

PRENATAL SLEEP AND PATHWAYS TO OFFSPRING CARDIOMETABOLIC RISK - PROJECT SUMMARY CARDIOVASCULAR DISEASE (CVD) IS THE LEADING CAUSE OF DEATH IN THE US, WITH SIGNIFICANT DISPARITIES BY SOCIOECONOMIC STATUS AND RACE/ETHNICITY. THE DEVELOPMENTAL ORIGINS OF CVD BEGIN EARLY IN LIFE AND EVEN BEFORE BIRTH. DESPITE THE KNOWN IMPORTANCE OF EARLY LIFE FOR CVD RISK, THE PROCESSES AND PATHWAYS BY WHICH EARLY LIFE EXPERIENCES SHAPE CVD RISK REMAIN POORLY UNDERSTOOD. THIS PROPOSAL TESTS THE HYPOTHESIS THAT PRENATAL SLEEP, WHICH IS HIGHLY INTEGRATED WITH CIRCADIAN RHYTHMS AND INFLUENCES NUMEROUS PHYSIOLOGICAL SYSTEMS DURING PREGNANCY, IS AN UNDERSTUDIED PATHWAY TO POOR CHILD CARDIOVASCULAR HEALTH. EXISTING EVIDENCE RELYING PRIMARILY ON SUBJECTIVE SLEEP ASSESSMENTS DEMONSTRATES A CORRELATION BETWEEN PRENATAL SLEEP AND OFFSPRING CVD RISK. HOWEVER, CRITICAL GAPS IN THE LITERATURE THAT IMPEDE PROGRESS INCLUDE: 1) LACK OF INVESTIGATION OF PHYSIOLOGICAL PATHWAYS BY WHICH PRENATAL MATERNAL SLEEP IMPACTS OFFSPRING CVD RISK, 2) ABSENCE OF RIGOROUS AND OBJECTIVE MEASUREMENTS OF PRENATAL SLEEP (E.G., ACTIGRAPHY) LONGITUDINALLY ACROSS PREGNANCY IN THE CONTEXT OF OTHER MEASURES OF MATERNAL HEALTH, AND 3) LACK OF DENSE LONGITUDINAL FOLLOW-UP OF INFANT GROWTH AND DEVELOPMENT. THIS PROPOSAL INVESTIGATES THREE KEY PATHWAYS THAT ARE BOTH KNOWN TO BE IMPACTED BY PRENATAL SLEEP AND LINKED TO CVD RISK WILL BE EXAMINED: MATERNAL BIOLOGICAL PROCESSES (STRESS-MEDIATING AND INFLAMMATORY PATHWAYS), CHILD BIOLOGICAL PROCESSES (INFANT GROWTH TRAJECTORIES, ADIPOSITY) AND CHILD BEHAVIOR (SLEEP, NEGATIVE EMOTIONALITY, SELF- REGULATION). TO INVESTIGATE THESE PATHWAYS, THREE AIMS WILL BE TESTED. AIM 1 TESTS THE HYPOTHESIS THAT PRENATAL MATERNAL SLEEP TRAJECTORIES PREDICT PRENATAL MATERNAL BIOLOGICAL PATHWAYS THAT MAY INFLUENCE OFFSPRING CVD RISK, INCLUDING INCREASED CIRCULATING INFLAMMATORY BIOMARKERS AND ALTERED DIURNAL SALIVARY CORTISOL DURING EACH TRIMESTER OF PREGNANCY. AIM 2 TESTS THE HYPOTHESIS THAT PRENATAL MATERNAL SLEEP TRAJECTORIES PREDICT OFFSPRING BIOLOGICAL PATHWAYS TO CVD RISK, INCLUDING ACCELERATED OFFSPRING GROWTH TRAJECTORIES AND GREATER BODY FAT PERCENTAGE THROUGH 6 MONTHS POSTNATAL. AIM 3 TESTS THE HYPOTHESIS THAT PRENATAL MATERNAL SLEEP TRAJECTORIES PREDICT OFFSPRING BEHAVIORAL CONTRIBUTORS TO CVD RISK, INCLUDING INFANT SLEEP, NEGATIVE EMOTIONALITY, AND SELF-REGULATION. AIMS WILL BE EVALUATED IN A SAMPLE OF 300 PRIMARILY LOW-INCOME AND RACIALLY- AND ETHNICALLY DIVERSE ENGLISH- AND SPANISH- SPEAKING PREGNANT INDIVIDUALS FROM DENVER HEALTH HOSPITAL AUTHORITY, A COMMUNITY SAFETY-NET HOSPITAL THAT SERVES THE LARGEST PROPORTION OF UNINSURED AND MEDICAID PATIENTS IN THE DENVER AREA.

MRI DEVELOPMENT: ENABLING RESEARCH IN NATURAL COMMUNICATION WITH VIRTUAL TUTORS, THERAPISTS, AND ROBOTIC COMPANIONS

MODELING CONFORMATIONAL ENSEMBLES OF THE DISORDERED PROTEINS

I/UCRC: NOVEL HIGH VOLTAGE/TEMPERATURE MATERIALS AND STRUCTURES

DECREASING REPEAT PREGNANCY AMONG PREGNANT AND PARENTING TEENS

COLLABORATIVE RESEARCH: THE CAUSES AND CONSEQUENCES OF ADAPTIVE RADIATION IN ANIMAL COMMUNICATION, FROM INDIVIDUALS TO COMMUNITIES -UNDERSTANDING HOW NEW, NOVEL TRAITS ARISE AND PERSIST IS CHALLENGING BECAUSE OBSERVING THIS PROCESS IN REAL TIME IS RARE?IT REQUIRES BEING IN THE RIGHT PLACE AT THE RIGHT TIME. YET, RAPID TRAIT CHANGE IS ONE MECHANISM BY WHICH ORGANISMS COULD RESPOND TO ONGOING ENVIRONMENTAL CHALLENGES, AND THE ORIGINS OF NOVELTY ARE CRITICAL TO OUR UNDERSTANDING OF HOW BIOLOGICAL VARIETY ARISES. THIS PROJECT CAPITALIZES ON THE RECENT EMERGENCE OF SEVERAL NEW, NOVEL CRICKET MATING SONGS IN THE PACIFIC FIELD CRICKET. THESE CRICKETS WERE RECENTLY INTRODUCED TO HAWAII WHERE THE DULCET MATING SONGS PRODUCED BY MALES ALSO ATTRACT AN INTRODUCED, LETHAL EAVESDROPPING FLY. OVER ALMOST 20 YEARS, THE PIS HAVE DIRECTLY OBSERVED THE DEVELOPMENT OF SEVERAL NEW, QUIET SONG TYPES THAT ALLOW COVERT COMMUNICATION, ATTRACTING FEMALE MATES BUT NOT THE EAVESDROPPING FLIES. USING A COMBINATION OF FIELD AND LAB EXPERIMENTS, THE RESEARCHERS AIM TO WATCH TRAIT AND BEHAVIORAL CHANGE PROCEED IN REAL TIME TO LEARN HOW NOVELTY ARISES IN ANIMAL COMMUNICATION, AND TO EXPLORE THE CONSEQUENCES FOR THE COMMUNITY OF INTERACTING ORGANISMS. MOREOVER, THE PROJECT WILL IMPACT THE PUBLIC UNDERSTANDING OF SCIENCE THROUGH 1) COLLABORATIVE K-16 MENTORSHIP PROGRAMS IN HAWAII, 2) PODCAST EPISODES THAT SHARE THE RESEARCH GLOBALLY, AND 3) THE PRODUCTION OF FOOD ITEMS INSPIRED BY THIS RESEARCH, DESIGNED AND PRODUCED BY RESEARCH PARTICIPANTS, AND SHARED WITH THE COMMUNITY TO CATALYZE CONVERSATIONS ABOUT ANIMAL COMMUNICATION. EVOLUTIONARY NOVELTY IS READILY DETECTABLE AT MACROEVOLUTIONARY SCALES, BUT THE MICROEVOLUTIONARY PROCESSES THAT RESULT IN NOVELTY REMAIN RELATIVELY UNKNOWN AND EXTREMELY CHALLENGING TO STUDY. THIS PROJECT CAPITALIZES ON AN UNPRECEDENTED OPPORTUNITY ? THE ONGOING RAPID DEVELOPMENT OF NEW SIGNALS IN THE INCIPIENT PHASES OF RADIATION ? TO STUDY HOW A PHENOTYPE THAT HAS BEEN STABLE FOR MILLENNIA DIVERGES FROM THE ANCESTRAL TO GENERATE A PLETHORA OF NEW SIGNAL TYPES. IN DOING SO, THE PIS WILL ADDRESS FUNDAMENTAL AND OUTSTANDING QUESTIONS ABOUT THE ORIGINS OF EVOLUTIONARY NOVELTY, WHICH IS CRITICAL TO BIOLOGICAL VARIETY. THIS INTEGRATIVE PROJECT ADDRESSES FOUR AIMS USING A COMBINATION OF LONGITUDINAL FIELD STUDIES, CONTROLLED EXPERIMENTS CONDUCTED IN THE LAB AND IN FIELD-BASED MESOCOSMS, AND DEVELOPMENT OF NEW THEORY. THE INVESTIGATORS WILL 1) CHARACTERIZE SIGNAL VARIETY, MECHANISTIC UNDERPINNINGS, AND EVOLUTIONARY DYNAMICS DURING AN ONGOING NATURAL RADIATION, 2) INVESTIGATE THE UNDERAPPRECIATED HYPOTHESIS THAT RELAXED RECEIVER PREFERENCES FACILITATE THE EVOLUTION OF NOVEL ANIMAL SIGNALS, 3) EXAMINE THE IMPACTS OF SIGNAL EVOLUTION FOR HOST-PARASITE DYNAMICS IN A MULTI-HOST ASSEMBLAGE AND TEST HOW ALTERNATIVE HOST SPECIES RECIPROCALLY IMPACT SIGNAL EVOLUTION, AND 4) DEVELOP THEORY TO EXAMINE THE CAUSES AND CONSEQUENCES OF NOVEL SIGNAL EVOLUTION THAT ARE TESTED IN LATER RESEARCH AIMS. THE INVESTIGATORS WILL INTERROGATE AN ONGOING MATING SIGNAL RADIATION AT THE INDIVIDUAL, POPULATION, AND COMMUNITY LEVELS TO UNDERSTAND HOW NOVEL TRAITS ARISE, SPREAD, FAIL, SUCCEED, AND IMPACT OTHERS. THE DYNAMIC AND CHARISMATIC INSECT STUDY SYSTEM PROVIDES OUTSTANDING OPPORTUNITIES TO ENGAGE BROADLY WITH NON-EXPERT AUDIENCES. THIS AWARD IS FUNDED JOINTLY BY THE DIVISION OF INTEGRATIVE ORGANISMAL SYSTEMS ? BEHAVIORAL SYSTEMS CLUSTER AND THE DIVISION OF EVOLUTIONARY BIOLOGY ? EVOLUTIONARY PROCESSES CLUSTER. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

UNKNOWN TITLE

USING MARRIAGE EDUCATION TO FOSTER INVESTMENT IN FATHERHOOD: A LONG-TERM COMPARISON OF INDIVIDUAL VS. COUPLES LEVEL INTE

REGULATION OF MITOCHONDRIAL OXIDATIVE STRESS BY BCL-2 FAMILY PROTEINS

LINKING TAU FILAMENT STRUCTURE TO PHENOTYPIC DIVERSITY IN HUMAN TAUOPATHIES

CAREER: INTEGRATING CONTEMPORARY EVOLUTION OF ANIMAL COMMUNICATION IN THE FIELD WITH SCIENCE COMMUNICATION IN OUR COMMUNITIES

VOLUMETRIC ANALYSIS OF EPITHELIAL MORPHOGENESIS WITH HIGH SPATIOTEMPORAL RESOLUTION - PROJECT SUMMARY HOW EPITHELIAL SHEETS REMODEL THEMSELVES TO ADOPT NEW TISSUE CONFORMATIONS THROUGH CHANGES IN NEIGHBOR RELATIONSHIPS AND CELL SHAPE DYNAMICS HAS BEEN A KEY QUESTION IN DEVELOPMENT AND DISEASE. INTERESTINGLY, MANY OF THE PIONEERING STUDIES PERFORMED IN MODEL SYSTEMS HAVE LARGELY BEEN CONFINED TO 2D ANALYSIS, AND HAVE OFTEN BEEN CHALLENGED TO IMAGE CELL BEHAVIORS THAT OCCUR IN BASAL REGIONS THAT LIE DEEPER INTO THE TISSUE. THE INTERCALATION MOVEMENTS THAT OCCUR DURING TISSUE ELONGATION IN THE DROSOPHILA GASTRULA HAVE BEEN A CLASSIC SYSTEM FOR UNDERSTANDING EPITHELIAL REMODELING, AND HAVE BEEN FUNDAMENTAL TO INFORMING THE DEVELOPMENTAL PARADIGMS THAT DESCRIBE HOW CELLS CAN CHANGE POSITION IN AN ADHERENT EPITHELIUM. NEARLY ALL OF THE STUDIES IN THIS SYSTEM HAVE BEEN CONFINED TO 2D ANALYSIS OF APICAL EVENTS IN THE EARLY FLY EMBRYO, AND NO STUDIES TO DATE HAVE SYSTEMATICALLY ANALYZED THE FULL 3D BEHAVIORS THAT DRIVE EPITHELIAL REMODELING AND TISSUE EXTENSION IN THE DROSOPHILA EMBRYONIC EPITHELIUM. THUS, ONE OF THE BIGGEST REMAINING QUESTIONS IN THE FIELD IS HOW THE VOLUMETRIC NATURE OF EPITHELIAL CELLS AFFECTS FORCE PROPAGATION AND REMODELING OF THE CELL SURFACE ALONG THE ENTIRE APICAL-BASAL AXIS. FUNDAMENTAL QUESTIONS ON WHERE FORCES ORIGINATE FROM AS WELL AS HOW FAR AND FAST FORCES PROPAGATE ACROSS DIFFERENT APICAL-BASAL LAYERS HAVE REMAINED UNANSWERED. IN OUR PRELIMINARY ANALYSIS, WE HAVE BEEN SUCCESSFUL IN COMPLETING THE FIRST FULL 4D SEGMENTATION OF THE INTERCALATING DROSOPHILA EPITHELIUM THROUGH THE USE OF LATTICE LIGHT SHEET MICROSCOPY (LLSM). WE FIND THAT INTERCALATION CAN BE INITIATED AT ANY POSITION WE HAVE SURVEYED ALONG THE APICAL-BASAL AXIS. THIS IS STRIKING AS PREVIOUS STUDIES HAVE LARGELY IMPLICATED APICAL FORCE GENERATION, AND A SINGLE STUDY HAS SUGGESTED THAT CONTRACTILE FORCES CAN ALSO ORIGINATE FROM THE BASAL SURFACE OF THE EPITHELIUM. IN THE PROPOSED PROJECT, WE ARE DEVELOPING THE TOOLS TO PERFORM THE FIRST COMPREHENSIVE, QUANTITATIVE 3D ANALYSIS OF CELL INTERCALATION IN THE EARLY DROSOPHILA EMBRYO. WE WILL THEN DETERMINE THE MOLECULAR MECHANISMS DRIVING 3D FORCE GENERATION, AND WHETHER DIFFERENT MECHANICAL REGIMES EXIST ACROSS THE APICAL-BASAL AXIS. PRELIMINARY DATA SUGGESTS HIGHLY NOVEL DYNAMIC MYOSIN II AND F-ACTIN POPULATIONS THAT SHOW RAPID AXIAL PROPAGATION IN LATERAL AND BASAL REGIONS. THE 3D DISTRIBUTIONS OF THESE POPULATIONS ARE BEING MAPPED AND THE RELEVANT ACTIN NUCLEATING AND MYOSIN REGULATORY NETWORKS WILL BE DETERMINED. THESE RESULTS WILL PROVIDE THE FIRST COMPREHENSIVE UNDERSTANDING OF THE CORTICAL AND CONTRACTILE NETWORKS THAT DETERMINE THE MECHANICAL ENVIRONMENT OF A GASTRULATING EPITHELIUM. WE WILL ALSO USE 3D DATA SETS IN WILD-TYPE AND FUNCTIONALLY COMPROMISED BACKGROUNDS TO EXAMINE HOW EPITHELIAL FORCES PROPAGATE ALONG APICAL-BASAL AND PLANAR DIMENSIONS USING TOPOLOGICAL MAPPING METRICS. WE WILL DETERMINE HOW FAR, AND AT WHAT VELOCITIES, CONTRACTILE FORCES SPREAD IN AN INTACT, DEVELOPING EPITHELIUM. THESE RESULTS WILL GIVE FUNDAMENTAL ANSWERS INTO HOW THE VISCOUS CYTOPLASM AND ELASTIC CELL CORTEX RESPOND TO FORCE-DRIVEN DISPLACEMENTS, AND HOW THESE DISPLACEMENTS SPREAD WITHIN INDIVIDUAL CELLS AND ACROSS TISSUES TO DRIVE NEW TISSUE TOPOLOGIES.

CONTROL OF CELL RATCHETING ENGAGEMENT DURING EPITHELIAL MORPHOGENESIS - PROJECT SUMMARY FORCE GENERATION IN EPITHELIAL TISSUES IS OFTEN PULSATILE, WITH ACTOMYOSIN NETWORKS GENERATING HIGH-TENSION CONTRACTILE FORCES AT THE CELL CORTEX BEFORE CYCLICALLY DISASSEMBLING. THIS PULSED NATURE OF CYTOSKELETAL FORCES IMPLIES THAT THERE MUST BE CELLULAR PROCESSES TO EXTRACT UNIDIRECTIONAL CHANGES THAT DRIVE PROCESSIVE TRANSFORMATIONS IN CELL SHAPE. IN PREVIOUS WORK (JEWETT ET AL., 2017; MIAO ET AL., 2019), WE FOUND THAT CYTOSKELETAL FORCE GENERATION IS COORDINATED WITH ENDOCYTIC REMODELING OF THE PLASMA MEMBRANE THROUGH SBF- RAB35 TUBULAR COMPARTMENTAL FUNCTION TO STABILIZE CONTRACTED CELL SURFACES AND PERMIT THE SHRINKING OF CELL APICES (APICAL CONSTRICTION) OR CELL INTERFACES (CELL INTERCALATION). HOWEVER, HOW THIS MEMBRANOUS CELLULAR RATCHET BECOMES ENGAGED AT PARTICULAR CELL SURFACES REMAINS UNCLEAR. IN THE PROPOSED STUDIES, WE WILL EXAMINE THE INFORMATIONAL SIGNALS THAT ENGAGE RATCHETING AND DIRECT SBF/RAB35 COMPARTMENTAL BEHAVIORS TO CONTRACTING INTERFACES OR CELL APICES, AND IDENTIFY THE FUNDAMENTAL CHANGES IN OSCILLATORY DURATIONS, AMPLITUDES, FREQUENCIES, AND/OR DIRECTIONALITY THAT LEAD TO CONTRACTILE PROCESSIVITY. OUR PRELIMINARY DATA INDICATES THE PIP3 IS A CRITICAL DETERMINANT FOR RATCHETING ENGAGEMENT – THROUGH OUR PROPOSED WORK WE WILL PERFORM THE FIRST CHARACTERIZATION OF PHOSPHATIDYLINOSITOL PHOSPHATES (PIPS) IN PROVIDING LIPID-BASED MEMBRANE CUES FOR MORPHOGENESIS AND GASTRULATION/RATCHETING DYNAMICS IN THE EARLY DROSOPHILA EMBRYO. IN THE FIRST AIM, WE WILL ALSO ANALYZE HOW THE PLASMA MEMBRANE ULTRASTRUCTURE IS REMODELED BY RATCHETING PROCESSES AND DETERMINE IF PIP LEVELS ARE DEVELOPMENTALLY PATTERNED TO DRIVE APICAL CONSTRICTION DURING MESODERM INGRESSION. OUR PROJECT THEN MOVES TO A SYSTEMATIC IDENTIFICATION OF SBF AND RAB35 PROTEIN PARTNERS IN DIRECTING RATCHETING ENGAGEMENT, AND EXAMINES THE CELL SIGNALING PATHWAYS THAT DIRECT A “SWITCHING” BEHAVIOR OF CONTRACTILE FORCE GENERATION FROM THE APICAL SURFACE TO CELL INTERFACES. OUR DATA INDICATES THAT, IN THE ABSENCE OF JAK/STAT SIGNALING, THE SBF-RAB35 RATCHET BECOMES ENGAGED ON ALL APICAL SURFACES IN THE EMBRYO, RESULTING IN GLOBAL APICAL FLATTENING AND CONSTRICTION. FURTHER, OUR STUDIES WILL DEFINE IF A LARGER UPD-JAK-STAT-PI3K-PIP3-SBF- RAB35 PATHWAY OR IF TWO INDEPENDENT PATHWAYS (PIP3 AND JAK/STAT) HAVE BEEN COORDINATED TO REGULATE RATCHETING ENGAGEMENT. WE ALSO APPLY A NEW COMPUTATIONAL PHASE-BASED OSCULATING CIRCLE APPROACH TO DETECT ACTIVE PERIODS OF CONTRACTION AND EXPANSION DISPLACEMENTS. FINALLY, WE ARE DEVELOPING A NEW MITO-TAG ECTOPIC RELOCALIZATION ASSAY AS A MEASURE OF “SUFFICIENCY” OF RECRUITING FACTORS IN VIVO, AND EXAMINE IF THE AKT/MTOR PATHWAY REGULATES CELL RATCHETING, POTENTIALLY DEMONSTRATING A NEW, HIGHLY NOVEL FUNCTION OF AKT/MTOR IN CONTROLLING EPITHELIAL CELL TOPOLOGIES. THUS, THE PLANNED PROJECT HAS THE POTENTIAL TO ELUCIDATE A LARGE, REGULATORY HIERARCHY OF THE MECHANISMS THAT GUIDE ENGAGEMENT OF CELL RATCHETING IN EPITHELIAL TISSUES.

SLIDING VERTEX BEHAVIORS DURING EPITHELIAL MORPHOGENESIS AND TISSUE ELONGATION

P-BODY AND MIRNA-MEDIATED REGULATION OF NEUROPLASTICITY

ADAPTATION: DU MERISTEM - MOBILIZING EQUITY TO RAISE INCLUSIVITY IN STEM

TOPOLOGICALLY UNIQUE SCAFFOLDS IN PHOTOASSISTED DIVERSITY ORIENTED SYNTHESIS (PDO

MICROBIOTA METALLOPHORES: PROBING INTERACTIONS AND NUTRIENT DYNAMICS OF THE HUMAN GUT - PROJECT SUMMARY/ABSTRACT A HEALTHY HUMAN MICROBIOME IS INTRINSICALLY LINKED TO VITAL PHYSIOLOGICAL ASPECTS SUCH AS DEVELOPMENT, IMMUNE FUNCTION, AND NUTRITION. THE COMPOSITION AND FUNCTION OF THE HUMAN MICROBIOTA IS SIGNIFICANTLY INFLUENCED BY ACCESS TO KEY METAL MICRONUTRIENTS INCLUDING IRON, COPPER, ZINC, AND COBALT. ALTHOUGH MECHANISMS OF COMPETITION FOR METALS HAVE BEEN STUDIED IN METAL-LIMITED ENVIRONMENTAL SYSTEMS, HOW THE HUMAN MICROBIOTA ACQUIRES METALS AND RESPONDS TO CHANGES IN HOST METAL HOMEOSTASIS REMAINS UNDER INVESTIGATED, EVEN AS MICROORGANISMS MUST COMPETE WITH ONE ANOTHER FOR LIMITED RESOURCES AT METAL-LIMITED BODY SITES. PRODUCTION OF METALLOPHORES, SMALL- MOLECULE NATURAL PRODUCTS THAT BIND METALS WITH HIGH AFFINITY AND SELECTIVITY, CAN ENABLE COLONIZATION OF METAL- LIMITED ENVIRONMENTS; FOR EXAMPLE, WE RECENTLY SHOWED THAT ESCHERICHIA COLI NISSLE 1917 PERSISTS IN THE ZINC- LIMITED INFLAMED GUT BY PRODUCING ZINC-BINDING YERSINIABACTIN. METALLOPHORE-PRODUCTION CAN ALSO BENEFIT OTHER, NON-PRODUCER ORGANISMS IN MICROBIAL SYSTEMS, AS METALLOPHORES CAN BE SHARED GOODS IN COMPLEX MICROBIAL COMMUNITIES. RECENT EXAMPLES HAVE REVEALED THAT BACTEROIDES THETAIOTAOMICRON, A HUMAN COMMENSAL BACTERIUM, USES SIDEROPHORES PRODUCED BY OTHER BACTERIA FOR IRON ACQUISITION DURING IRON-LIMITATION. HOWEVER, DESPITE SIGNIFICANT NUMBERS OF METALLOPHORE BIOSYNTHETIC GENE CLUSTERS (BGCS) PRESENT IN METAGENOMICS SEQUENCING DATA FROM HUMAN-DERIVED MICROBIOTA SAMPLES, ELUCIDATION OF THE CHEMICAL STRUCTURES AND PROPERTIES OF THESE MICROBIAL MOLECULES REMAIN LIMITED BY VARIOUS ANALYTICAL, CHEMICAL, AND BIOLOGICAL CHALLENGES. THIS LACK OF RELIABLE METHODS PRECLUDES OUR UNDERSTANDING OF FUNCTIONAL ROLES OF THESE MOLECULES. THEREFORE, THE GOAL OF THIS PROPOSAL IS TO ELUCIDATE THE STRUCTURE AND FUNCTIONS OF MICROBIALLY-DERIVED METALLOPHORES AS MODULATING MICROBE-MICROBE AND COMMUNITY INTERACTIONS WITHIN HUMAN MICROBIOMES. TO ACCOMPLISH THIS, OUR LABORATORY WILL INVESTIGATE SEVERAL CRITICAL QUESTIONS, BROADLY THESE ARE: 1) WHAT METALLOPHORES ARE PRODUCED BY THE HUMAN MICROBIOTA AND HOW ARE THEY BIOSYNTHESIZED? 2) WHAT ARE THEIR METAL PREFERENCES AND SPECIFICITIES? 3) HOW DO THESE MOLECULES MODULATE MICROBIAL INTERACTIONS? 4) WHAT ARE THE EFFECTS OF ALTERED MICROBIAL INTERACTIONS? WITH THESE QUESTIONS IN MIND, WE DEVELOP DISCOVERY-BASED APPROACHES TO FIND UNCHARACTERIZED MICROBIAL METALLOPHORES, PURSUE CHEMICAL STRUCTURE ELUCIDATION AND CHARACTERIZATION OF BIOSYNTHESIS, AND INVESTIGATE GROWTH AND METAL ACQUISITION OF WILD-TYPE AND GENETIC DELETION MUTANTS (LACKING METALLOPHORE-PRODUCTION ABILITY) TO UNDERSTAND FUNCTIONAL ROLES OF THESE MOLECULES IN MONOCULTURE, CO-CULTURE, AND IN COMPLEX MICROBIAL MODEL SYSTEMS. ELUCIDATING THE METAL-UPTAKE MOLECULES AND MECHANISMS USED BY THE MICROBIOTA TO WITHSTAND ALTERED METAL HOMEOSTASIS MAY ALLOW FOR THE DEVELOPMENT OF MICROBIOME-BASED THERAPEUTICS, IDENTIFICATION OF MICROBIOME-DERIVED BIOMARKERS, AND AN IMPROVED UNDERSTANDING OF METAL IMBALANCES. THIS RESEARCH WILL PROVIDE FUNDAMENTAL INSIGHT HOW MEMBERS OF THE MICROBIOTA INTERACT THROUGH METAL COMPETITION, A KEY MECHANISM BY WHICH BOTH OPPORTUNISTIC INFECTIONS AND PROBIOTIC ORGANISMS ARE ESTABLISHED AND PERSIST WITHIN THE MICROBIOME.

OPIOID WORKFORCE EXPANSION PROGRAM- PROFESSIONAL

CAREER: THE GENES AND GENE NETWORKS UNDERLYING FERTILIZATION BARRIERS IN A HYBRID ZONE -REPRODUCTION REQUIRES COMPLEX INTERACTIONS BETWEEN MALES AND FEMALES AND, EVEN AFTER MATING, GAMETES, REPRODUCTIVE TRACTS AND THEIR SECRETIONS COORDINATE FOR SUCCESSFUL FERTILIZATION. DESPITE THEIR FUNDAMENTAL ROLE IN REPRODUCTION, POSTMATING TRAITS ARE OFTEN DRAMATICALLY DIFFERENT BETWEEN CLOSELY RELATED SPECIES AND CAN PREVENT SPECIES FROM SUCCESSFULLY INTERBREEDING. THIS SUGGESTS THAT POSTMATING TRAITS MAY PLAY A SPECIAL ROLE IN THE EVOLUTION OF NEW SPECIES AND THE DIVERSITY OF LIFE ON EARTH. THIS PROJECT WILL IDENTIFY THE UNDERLYING GENES AND GENE INTERACTIONS THAT CONTRIBUTE TO POSTMATING TRAIT DIFFERENCES BETWEEN TWO CLOSELY RELATED SPECIES. THE RESEARCH WILL PROVIDE GREATER UNDERSTANDING OF CRITICAL REPRODUCTIVE TRAITS AND THE EVOLUTION OF GENE NETWORKS. THE PROJECT WILL PROVIDE QUANTITATIVE TRAINING FOR UNDERGRADUATE STEM MAJORS AT THE UNIVERSITY OF DENVER. STUDENTS WILL GAIN CLASSROOM EXPERIENCE ANALYZING BIOLOGICAL DATA, IMPROVING THEIR PROBLEM-SOLVING SKILLS, BASIC PROGRAMMING, AND INTERROGATION OF BIOLOGICAL COMPLEXITY, WHICH WILL BETTER PREPARE STUDENTS FOR INCREASINGLY DATA-DRIVEN CAREERS IN STEM. THESE EDUCATIONAL RESOURCES AND TOOLS WILL BE DISSEMINATED WIDELY, CONTRIBUTING TO IMPROVED QUANTITATIVE BIOLOGY CURRICULUM. SOME OF THE MOST INTRICATE INTERGENOMIC INTERACTIONS OCCUR AFTER MATING, WHEN GAMETES, REPRODUCTIVE TRACT TISSUES, AND THEIR SECRETIONS BATTLE AND COORDINATE FOR FERTILIZATION. THESE POSTMATING TRAITS AND THEIR UNDERLYING GENES ARE SOME OF THE MOST RAPIDLY EVOLVING IN THE GENOME. THE RAPID DIVERGENCE IN POSTMATING TRAITS SUGGESTS THAT THEY MAY PLAY AN IMPORTANT ROLE IN SPECIATION, BUT AN OUTSTANDING QUESTION IS WHETHER THE EVOLUTION OF POSTMATING PREZYGOTIC BARRIERS DIFFERS FROM OTHER TYPES OF REPRODUCTIVE BARRIERS. THE PROJECT WILL INVESTIGATE THE EVOLUTION OF POSTMATING BARRIERS BETWEEN TWO SPECIES BY PAIRING IN-DEPTH CHARACTERIZATION OF GENE REGULATORY NETWORK DIVERGENCE WITH GENE EXPRESSION MAPPING OF POSTMATING BARRIER TRAITS. THESE ANALYSES WILL BE COMPARED TO VARIATION FOUND IN A NATURAL HYBRID ZONE TO EVALUATE THE EFFECTS OF SELECTION ON RECOMBINANT GENE REGULATORY NETWORKS. THE PROJECT WILL LEAD TO A BETTER UNDERSTANDING OF THE EVOLUTION OF GENE EXPRESSION AND PROVIDE INSIGHT INTO THE EVOLUTION AND DIVERSITY OF POSTMATING TRAITS. STUDENTS WILL ANALYZE DATA GENERATED THROUGH THIS PROJECT IN THE CLASSROOM, PROVIDING EXPERIENTIAL-LEARNING AND BUILDING STUDENTS' QUANTITATIVE TRAINING. THE DATA-FOCUSED CURRICULUM WILL TEACH STUDENTS TO UNDERSTAND GENETIC COMPLEXITY, SO THEY BETTER UNDERSTAND HUMAN DIFFERENCES AND APPLICATIONS OF BIOLOGICAL DATA, MAKING THEM BETTER PREPARED FOR INCREASINGLY DATA-DRIVEN CAREERS IN STEM AND TO INTERPRET DATA IN A SOCIETAL CONTEXT. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

A MULTI-SCALE FINITE ELEMENT MUSCULOSKELETAL MODELING FRAMEWORK APPLIED TO CURREN

POST-DOCTORAL PREP FELLOWSHIP AWARD FOR UNIVERSITY OF DENVER.

INFRARED MEASURMENTS OF ATMOSPHERIC CONSTITUENTS IN SUPPORT OF SATELI TTE MEASUREMENTS OF THE EARTH'

THE LINGUISTIC PHENOTYPE IN FAMILIAL DYSLEXIA

LIBRARIANS FOR THE 21ST CENTURY

MRI: DEVELOPMENT OF AN INNOVATIVE EPR SPECTROMETER

INNOVATION AND IMPROVEMENT PROJECT

FOSTERING RELATIONSHIPS TO ELEVATE LOW-INCOME LEARNERS IN COMPUTER SCIENCE -THIS PROJECT WILL CONTRIBUTE TO THE NATIONAL NEED FOR WELL-EDUCATED COMPUTER SCIENTISTS BY SUPPORTING THE RETENTION AND GRADUATION OF HIGH-ACHIEVING STUDENTS WITH DEMONSTRATED FINANCIAL NEED AT THE UNIVERSITY OF DENVER, A PRIVATE INSTITUTION COMMITTED TO THE PUBLIC GOOD. OVER ITS SIX-YEAR DURATION, THIS TRACK 1 PROJECT WILL PROVIDE SCHOLARSHIPS TO 19 UNIQUE FULL-TIME STUDENTS PURSUING BACHELOR?S DEGREES IN COMPUTER SCIENCE, A HIGH-DEMAND STEM FIELD. THIS PROJECT WILL OFFER FIRST-YEAR STUDENTS FOUR YEARS OF SCHOLARSHIP SUPPORT, DESIGNED TO ADDRESS THEIR FINANCIAL NEED AND SUPPORT THEIR ACADEMIC SUCCESS. THE PROJECT WILL IMPLEMENT A VARIETY OF HIGH-IMPACT ACTIVITIES, INCLUDING COHORT-BASED COURSES IN CALCULUS AND COMPUTER SCIENCE, PROFESSIONAL DEVELOPMENT MODULES, AND PEER AND FACULTY MENTORSHIP. SCHOLARS WILL ALSO PARTICIPATE IN A DEDICATED EARLY-START PROGRAM TO FOSTER DEVELOPMENT OF SOCIAL BONDS AND MAY ENGAGE IN PAID SUMMER RESEARCH EXPERIENCES AS THEY PROGRESS IN THEIR STUDIES. THIS INITIATIVE SEEKS TO BROADEN PARTICIPATION IN THE COMPUTING WORKFORCE BY ENSURING THAT LOW-INCOME STUDENTS COMPLETE THEIR DEGREES AND SUCCESSFULLY TRANSITION INTO THE TECHNOLOGY INDUSTRY OR GRADUATE PROGRAMS. THE PROJECT WILL INCLUDE A COMPREHENSIVE EVALUATION PLAN TO ASSESS THE RELATIVE EFFECTIVENESS OF FINANCIAL SUPPORT, ACADEMIC PROGRAMMING, AND SOCIAL CONNECTIONS. THE GOAL IS TO IDENTIFY THE MOST EFFECTIVE METHODS FOR SUPPORTING STUDENT RETENTION, PERSISTENCE, AND CAREER SUCCESS IN THE FIELD OF COMPUTER SCIENCE. THE OVERALL GOAL OF THIS PROJECT IS TO INCREASE STEM DEGREE COMPLETION OF HIGH-ACHIEVING LOW-INCOME UNDERGRADUATES WITH DEMONSTRATED FINANCIAL NEED. TO ACHIEVE THIS, THE PROJECT WILL ADDRESS FINANCIAL, ACADEMIC, AND SOCIAL BARRIERS THAT HINDER STUDENT SUCCESS. PROVIDING SCHOLARSHIPS TO ADDRESS UNMET FINANCIAL NEEDS WILL ENSURE THAT FINANCIAL CONSTRAINTS DO NOT IMPEDE ACADEMIC PROGRESS. STUDENTS WILL PARTICIPATE IN AN EARLY-START PROGRAM, COHORT-BASED COURSES WITH FACULTY MENTORS, AND PEER MENTORING THAT ALL FOSTER A STRONG SENSE OF BELONGING AND COMMUNITY, WHICH ARE CRITICAL FACTORS FOR PERSISTENCE AND SUCCESS IN STEM. THE PROJECT WILL ALSO OFFER PROFESSIONAL DEVELOPMENT OPPORTUNITIES, SUCH AS PAID SUMMER RESEARCH INTERNSHIPS AND CAREER PREPARATION WORKSHOPS, TO HELP STUDENTS GAIN PRACTICAL EXPERIENCE AND CAREER READINESS. THE RESEARCH WILL EXPLORE THE EFFECTIVENESS OF THE COMBINED INTERVENTIONS OF FINANCIAL AID, ACADEMIC PROGRAMMING, AND MENTORSHIP, IN IMPROVING RETENTION, ACADEMIC PERFORMANCE, AND GRADUATION RATES. IT WILL ALSO EXAMINE HOW THESE STRATEGIES CONTRIBUTE TO STUDENTS' LONG-TERM SUCCESS IN STEM FIELDS. EVALUATION WILL BE BASED UPON QUANTITATIVE DATA, SUCH AS GRADUATION RATES AND GPA, AS WELL AS QUALITATIVE FEEDBACK FROM PARTICIPANTS. RESULTS WILL BE DISSEMINATED THROUGH ACADEMIC PUBLICATIONS, CONFERENCES, AND A PROJECT WEBSITE TO INFORM BEST PRACTICES FOR SUPPORTING LOW-INCOME STUDENTS IN STEM. THIS PROJECT IS FUNDED BY NSF'S SCHOLARSHIPS IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS PROGRAM, WHICH SEEKS TO INCREASE THE NUMBER OF 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 STUDENTS WITH FINANCIAL NEED. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

IN SITU MEASUREMENTS OF AEROSOL SIZE DISTRUBUTIONS/SATELLITE VALIDATION AND THE RESPONSE AND EFFECTS OF ATMOSPHERIC AEROSOLS ON GLOBAL CHANGE: WE PRO

BEHAVIORAL HEALTH WORKFORCE EDUCATION AND TRAINING (BHWET) PROGRAM

BEHAVIORAL HEALTH WORKFORCE EDUCATION AND TRAINING (BHWET) PROGRAM

COLLABORATIVE RESEARCH: EDGE FGT: CELL TYPE-SPECIFIC TOOLS FOR THE STUDY OF GENE FUNCTION IN SPONGES. -SPONGES ARE AQUATIC INVERTEBRATES WITH MANY IMPORTANT CHARACTERISTICS. STUDYING THESE ANIMALS PROVIDES INSIGHT INTO THE EVOLUTION OF COMPLEXITY, SPECIALIZED CELL TYPES, AND INTERACTIONS WITH MICROBES. SPONGES ALSO PRODUCE MANY NATURAL COMPOUNDS RELEVANT TO THE PHARMACEUTICAL AND BIOTECHNOLOGY SECTORS. YET DESPITE THEIR SIGNIFICANCE ACROSS THESE MANY SCIENTIFIC AREAS, RESEARCH PROGRESS HAS BEEN LIMITED BY THE LACK OF TOOLS TO MANIPULATE SPONGE GENES AND CELLS. THIS PROJECT BUILDS ON A RECENT TECHNICAL ADVANCE THAT ENABLES EFFICIENT DELIVERY AND EXPRESSION OF GENETIC MATERIAL IN SPONGES. THIS PROJECT WILL (1) DEVELOP A COMPREHENSIVE LIBRARY OF MOLECULAR TOOLS FOR VISUALIZING AND CONTROLLING GENE ACTIVITY IN SPECIFIC SPONGE CELLS, (2) ESTABLISH STANDARDIZED, REPRODUCIBLE PROTOCOLS FOR GENOME EDITING, AND (3) PROVIDE DIRECT TRAINING OPPORTUNITIES TO SPEED THE ADOPTION OF THESE METHODS BY RESEARCHERS. ALL METHODS AND TOOLS WILL BE MADE OPENLY AVAILABLE TO ACCELERATE COMMUNITY-WIDE UPTAKE. BY TRANSFORMING SPONGES INTO A SYSTEM WHERE GENES CAN BE READILY STUDIED, THIS PROJECT WILL EMPOWER NEW LINES OF INVESTIGATION ACROSS DEVELOPMENTAL BIOLOGY, IMMUNOLOGY, CELL EVOLUTION, AND NATURAL PRODUCT DISCOVERY. AT THE CORE OF THIS EFFORT IS THE DEVELOPMENT OF CELL TYPE-SPECIFIC GENETIC TOOLS FOR THE FRESHWATER SPONGE SPONGILLA LACUSTRIS, A WIDELY USED LABORATORY MODEL IN SPONGE BIOLOGY. BUILDING ON A PUBLISHED SINGLE-CELL ATLAS AND A HIGH-EFFICIENCY ELECTROPORATION METHOD, THE RESEARCH TEAM WILL (1) OPTIMIZE TRANSFECTION CONDITIONS USING A FACTORIAL DESIGN AND QUANTITATIVE REPORTER ASSAYS, (2) CREATE A MODULAR PLASMID TOOLKIT FEATURING CELL TYPE-SPECIFIC PROMOTERS, CODON-OPTIMIZED FLUORESCENT PROTEINS, AND SUBCELLULAR TARGETING SIGNALS, AND (3) IMPLEMENT CRISPR/CAS9 GENOME EDITING TO GENERATE STABLE TRANSGENIC LINES. THESE TOOLS WILL ENABLE RESEARCHERS TO DIRECTLY TEST GENE FUNCTION IN VIVO AND INVESTIGATE CELLULAR MECHANISMS THAT HAVE BEEN INACCESSIBLE IN SPONGES UNTIL NOW. THE PROJECT WILL ALSO SERVE AS A MODEL FOR EXTENDING GENETIC TECHNOLOGIES TO OTHER EXPERIMENTALLY CHALLENGING BUT SCIENTIFICALLY IMPORTANT ORGANISMS. THIS RESEARCH WILL DEVELOP NEW BIOTECHNOLOGY THAT WILL BE MADE AVAILABLE TO THE SCIENTIFIC COMMUNITY. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

MRI DEVELOPMENT: HETEROGENEOUS, AUTONOMIC WIRELESS CONTROL NETWORKS FOR SCALABLE CYBER-PHYSICAL SYSTEMS

LIBRARIANS FOR THE 21ST CENTURY

INNOVATIVE AI SYSTEMS FOR NURTURING AND ASSESSING CREATIVITY IN K-12 LEARNING ENVIRONMENTS -CREATIVE THINKING IS FUNDAMENTAL TO SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) SUCCESS, YET CURRENT METHODS FOR ASSESSING AND NURTURING STUDENT CREATIVITY ARE COSTLY, TIME-INTENSIVE, AND OFTEN INACCESSIBLE TO UNDER-RESOURCED SCHOOLS. THIS PROJECT ADDRESSES THIS CRITICAL NATIONAL NEED BY DEVELOPING ARTIFICIAL INTELLIGENCE-POWERED TOOLS TO MAKE CREATIVITY ASSESSMENT AND MENTORING BOTH SCALABLE AND BROADLY ACCESSIBLE IN K-12 EDUCATION. THE RESEARCH TEAM WILL CREATE AND EVALUATE TWO INTERCONNECTED SYSTEMS THAT EVALUATE STUDENT CREATIVE OUTPUT AND PROVIDE REAL-TIME GUIDANCE DURING PROBLEM-SOLVING ACTIVITIES. BY MAKING THESE TOOLS FREELY AVAILABLE ON THE WEB, THE PROJECT WILL ENABLE EDUCATORS NATIONWIDE TO SYSTEMATICALLY MONITOR AND ENHANCE STUDENT CREATIVITY. AS ARTIFICIAL INTELLIGENCE INCREASINGLY BECOMES PART OF PROFESSIONAL CREATIVE WORK, THE PRODUCTS FROM THIS WORK WILL ALSO PREPARE STUDENTS FOR A TRANSFORMED FUTURE WHERE HUMAN-MACHINE COLLABORATION IN CREATIVE TASKS WILL BE COMMONPLACE. THE PROJECT WILL DEVELOP TWO CORE ARTIFICIAL INTELLIGENCE SYSTEMS. THE FIRST, OCSAI PRIME, REPRESENTS A TASK-AGNOSTIC CREATIVITY ASSESSMENT MODEL THAT USES SUPERVISED FINE-TUNING TO EVALUATE BOTH ORIGINALITY AND APPROPRIATENESS ACROSS DIVERSE CREATIVE CHALLENGES, MOVING BEYOND CURRENT TOOLS THAT ARE LIMITED TO SPECIFIC TASKS. THE SECOND, CREATIVITY COMPANION, EMPLOYS REINFORCEMENT LEARNING WITH HUMAN FEEDBACK TO CREATE AN INTERACTIVE FACILITATION TOOL THAT GUIDES STUDENTS THROUGH CREATIVE IDEATION IN REAL-TIME. THE COMPANION WILL BE TRAINED USING REWARD MODELING BASED ON OCSAI PRIME'S ASSESSMENTS COMBINED WITH HUMAN FEEDBACK TO OPTIMIZE ITS ABILITY TO ENHANCE STUDENT CREATIVE THINKING. BOTH SYSTEMS WILL UNDERGO RIGOROUS EVALUATION THROUGH A RANDOMIZED CONTROLLED TRIAL DESIGN IN MIDDLE SCHOOL CLASSROOMS ACROSS THREE GEOGRAPHICALLY DIVERSE DISTRICTS, COMPARING STUDENT CREATIVITY OUTCOMES, ENGAGEMENT, AND LEARNING PERSISTENCE BETWEEN ARTIFICIAL INTELLIGENCE-ASSISTED AND CONTROL GROUPS. THE RESEARCH WILL INCLUDE COMPREHENSIVE DEMOGRAPHIC ANALYSIS TO ENSURE BROAD BENEFITS WHILE CONTRIBUTING NEW KNOWLEDGE ABOUT COMPUTATIONAL CREATIVITY ASSESSMENT, HUMAN-ARTIFICIAL INTELLIGENCE CO-CREATIVITY, AND EDUCATIONAL TECHNOLOGY INTEGRATION IN STEM LEARNING ENVIRONMENTS. THIS PROJECT IS FUNDED BY THE RESEARCH ON INNOVATIVE TECHNOLOGIES FOR ENHANCED LEARNING (RITEL) PROGRAM THAT SUPPORTS EARLY-STAGE EXPLORATORY RESEARCH IN EMERGING TECHNOLOGIES FOR TEACHING AND LEARNING. 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.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

THE EVOLUTION OF CELL-CELL ADHESION AND THE ASSEMBLY OF EPITHELIAL TISSUES WERE INTIMATELY COUPLED TO THE EVOLUTION OF COMPLEX MULTICELLULARITY. EPITHELIA HAVE ESSENTIAL ROLES FROM ACTING AS AN ENVIRONMENTAL BARRIER AND PARTITIONING ORGANISMS INTO DISCRETE COMPARTMENTS TO COORDINATING MORPHOGENESIS DURING DEVELOPMENT. WE PROPOSE TO EXPLORE THE EARLY EVOLUTION OF EPITHELIA - STRUCTURES THAT WE PREDICT WOULD BE ADVANTAGEOUS IN COMPLEX LIFE FORMS ANYWHERE TO UNDERSTAND INNOVATIONS IN THE ANIMAL STEM-LINEAGE THAT CONTRIBUTED TO THE EVOLUTION OF ANIMAL BODY PLANS. DEFINING FEATURES OF EPITHELIA ARE THE ADHESION MODULES THAT TETHER CELLS TO EACH OTHER ENABLE FOLDING AND BENDING OF SHEETS AND TUBES OF CELLS DEFINE APICAL/BASAL POLARITY AND SPECIFY GENE EXPRESSION. OUR FOCUS IS ON THE CADHERIN/CATENIN MODULE (CCM) WHICH FORMS THE MOLECULAR FOUNDATION OF ADHERENS JUNCTIONS IN ALL STUDIED BILATERIAN TISSUES AND IS HYPOTHESIZED TO HAVE EVOLVED IN CONCERT WITH ANIMAL MULTICELLULARITY. FORMATION OF THESE JUNCTIONS APPEARS TO BE THE EARLIEST EVENT IN EPITHELIAL MORPHOGENESIS AND IT SERVES AS A SPATIAL LANDMARK FOR FORMATION OF OTHER TYPES OF CELL-CELL JUNCTIONS. EXPERIMENTAL DISRUPTION OF THE CCM PERTURBS EPITHELIAL DEVELOPMENT INTEGRITY AND POLARITY. OUR OBJECTIVE IS TO EXAMINE HOW AN ANCIENT ACTINMYOSIN SCAFFOLD COMMON TO ALL EUKARYOTES WAS RECRUITED BY THE MORE RECENTLY EVOLVED CCM TO COORDINATE CELL INTERACTIONS NECESSARY FOR MULTICELLULARITY AND TISSUE DIVERSITY. IMPORTANTLY THIS MULTI-FUNCTIONAL MODULE IS PRESENT IN ALL ANIMAL LINEAGES AND POTENTIALLY SATISFIES ALL REQUIREMENTS FOR MULTICELLULAR ADHESION AND MORPHOGENESIS - CADHERINS ENABLE ADHESION BETWEEN CELLS AND CATENINS BIND TO THE ACTIN SCAFFOLD TO ORGANIZE MULTICELLULAR ARCHITECTURE AND CAN SIGNAL TO THE NUCLEUS TO CHANGE GENE EXPRESSION. WE HAVE A DETAILED MECHANISTIC UNDERSTANDING OF THE COMPONENT PARTS AND FUNCTION OF THIS ADHESION MODULE IN BILATERIAN ANIMALS BUT THE EARLY EVOLUTION OF THIS MODULE IS FAR LESS CLEAR. OUR APPROACH IS TO EXAMINE THE FUNCTION OF CCM PROTEINS IN KEY NON-BILATERIAN ANIMAL LINEAGES INCLUDING CNIDARIANS CTENOPHORES AND SPONGES. LITTLE IS KNOWN ABOUT HOW THEY FUNCTION IN THESE ORGANISMS NOR HOW THEY EVOLVED TO TAKE ON NOVEL ROLES TO ENABLE MULTICELLULAR COMPLEXITY. WHAT IS THE MINIMAL SET OF ADHESION PROTEINS NECESSARY FOR THE COORDINATION OF CELL-CELL ADHESION AND LINKAGE TO THE ACTIN CYTOSKELETON AND ARE BASIC FUNCTIONS OF THIS SET SHARED BY ALL ANIMALS? THE CCM IS A LIKELY CANDIDATE AND WE WILL TEST THIS HYPOTHESIS BY OBSERVING CCM PROTEINS IN CELLS AND TISSUES OF NON-BILATERIAN METAZOANS DURING MORPHOGENESIS BY EXAMINING PHYSICAL INTERACTIONS BETWEEN THESE PUTATIVE EPITHELIAL PROTEINS WITH COMPARATIVE BIOCHEMISTRY AND USING FUNCTIONAL GENETICS TO DELETE AND REPLACE GENES PUTATIVELY INVOLVED IN TISSUE MORPHOGENESIS AND CELL-CELL ADHESION. OTHER POTENTIAL CADHERIN-RELATED PROTEINS SIGNALING AND ACTIN-BINDING PROTEINS WILL BE IDENTIFIED USING BIOINFORMATIC DISSECTION OF GENOMES. RESULTS WILL BE INTEGRATED WITH KNOWN PROPERTIES OF THE CADHERIN-CATENIN ADHESION MODULE IN BILATERIANS. OUR EXPERIMENTAL APPROACH IS UNUSUALLY COMPREHENSIVE AND INTERDISCIPLINARY FOR BROAD COMPARATIVE STUDIES AND INVOLVES A DIVERSE TEAM TO TACKLE THIS PROBLEM THAT COMPRISES EVOLUTIONARY-DEVELOPMENTAL BIOLOGISTS (LOWE/MARTINDALE) AN EVOLUTIONARY-CELL BIOLOGIST (NICHOLS) AND A BIOCHEMIST/STRUCTURAL BIOLOGIST (WEIS). THE CAPACITY TO DEVELOP ROBUST TISSUES THAT PROVIDE A PHYSICAL AND CHEMICAL BARRIER TO THE OUTSIDE ENVIRONMENT AND FACILITATE TISSUE SPECIALIZATION IS A BASIC CHARACTERISTIC OF COMPLEX LIFE. THE WORK OUTLINED IN THIS PROPOSAL ADDRESSES FUNDAMENTAL QUESTIONS ABOUT THE ASSEMBLY OF A KEY CELLULAR INNOVATION EARLY IN ANIMAL EVOLUTION EPITHELIA ARE AT THE CORE OF HYPOTHESES OF THE EVOLUTION OF MULTICELLULARITY AND ANIMAL BODY-PLAN COMPLEXITY AND THEREFORE CENTRAL TO THE NASA EXOBIOLOGY MISSION OF UNDERSTANDING ADVANCED LIFE.

SYNTHETIC PROTEIN MIMETICS-BASED SPECIFIC TARGETING AND DEGRADATION OF TDP-43 AGGREGATION ASSOCIATED WITH ALS

INVESTIGATING THE NEURAL SYSTEMS THAT SUPPORT THE BENEFICIAL EFFECTS OF POSITIVE EMOTION ON STRESS REGULATION

CAREER: ELUCIDATING THE CHEMISTRY OF BIOLOGICAL LANTHANIDE CHELATORS FOR RARE EARTH ELEMENT SEPARATION -THE CHEMISTRY OF LIFE PROCESSES PROGRAM IN THE CHEMISTRY DIVISION IS FUNDING DR. ALLEGRA ARON FROM THE UNIVERSITY OF DENVER TO IDENTIFY AND CHARACTERIZE SMALL MOLECULES PRODUCED BY BACTERIA FOUND IN SOIL AND ON PLANTS THAT BIND TO LANTHANIDE (LN) METALS. LN METALS, SUCH AS LANTHANUM AND NEODYMIUM, ARE RARE EARTH ELEMENTS (REES) THAT ARE RAW MATERIALS FOR THE PRODUCTION OF CRITICAL TECHNOLOGICAL AND NATIONAL SECURITY COMPONENTS (SUCH AS COMPUTERS, CELLPHONES AND RADAR/SONAR SYSTEMS). THE OBJECTIVE OF THIS PROJECT IS TO DEFINE THE STRUCTURAL AND LN BINDING PROPERTIES OF THESE BACTERIAL MOLECULES, WITH THE LONG-TERM GOAL OF DEVELOPING BIOLOGY-BASED METHODS FOR THE SEPARATION, ISOLATION AND RECOVERY OF REES. THE EDUCATIONAL PLAN WILL EDUCATE THE NEXT GENERATION OF SCIENTISTS BY PROVIDING MERIT-BASED PAID LABORATORY INTERNSHIPS TO DENVER PUBLIC HIGH SCHOOL STUDENTS IN PARTICIPATING CHEMISTRY LABS AND ACROSS THE COLLEGE OF NATURAL SCIENCES. IN ADDITION, GRADUATE STUDENTS AND RESEARCHERS WILL BE PREPARED FOR INTERDISCIPLINARY RESEARCH THROUGH WEEKLY VIRTUAL OFFICE HOURS AND IN-PERSON SUMMER SCHOOL WORKSHOPS HOSTED BY A COLLABORATIVE VIRTUAL METABOLOMICS LABORATORY. THE OVERALL OBJECTIVE OF THIS PROPOSAL IS TO UNDERSTAND THE ORIGINS OF METAL- AND UPTAKE-SELECTIVITY THROUGH THE ISOLATION AND CHARACTERIZATION OF LN-CHELATORS WITH VARIED STRUCTURES ISOLATED FROM ONE-CARBON METABOLIZING METHYLOTROPHIC BACTERIA. RESULTS FROM PRELIMINARY GENOME MINING SUGGEST SIGNIFICANT STRUCTURAL VARIATION EXISTS ACROSS BIOLOGICAL LN-CHELATORS, SUCH THAT SPECIFICITY MAY EXIST IN BOTH METAL-BINDING AND IN MOLECULAR RECOGNITION. LIQUID CHROMATOGRAPHY-BASED MASS SPECTROMETRY ALONG WITH COMPUTATIONAL WORKFLOWS, STATISTICAL PIPELINES, AND METAL-INFUSION EXPERIMENTS WILL BE USED TO DISCOVER NOVEL CHELATORS FROM FIVE ORGANISMS IN THE METHYLOBACTERIA AND METHYLORUBRUM FAMILIES OF BACTERIA. THE CHEMICAL STRUCTURES AND SELECTIVITY IN BINDING BETWEEN LN AND IRON (A MORE UBIQUITOUS COMPETITOR METAL) OF PUTATIVE CHELATORS WILL BE CHARACTERIZED THROUGH VARIOUS SPECTROSCOPY METHODS RANGING FROM UV-VISIBLE TO MAGNETIC RESONANCE SPECTROSCOPIES. FINALLY, THE BIOLOGICAL ROLES OF THESE CHELATORS IN THE ACCUMULATION OF LN VERSUS IRON WILL BE DETERMINED USING A HOST OF MOLECULAR BIOLOGY TECHNIQUES, ALONG WITH ASSESSMENT OF METAL UPTAKE. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

IDBR: RAPID SCAN ELECTRON PARAMAGNETIC RESONANCE SPECTROMETER

IN SITU MEASURMENTS OF AEROSOL SIZE DISTRUBUTIONS & COLLECTION OF PARTICLES FOR ANALYTICAL ELECT

TESTING CORTISOL DYSREGULATION AS A MEDIATOR BETWEEN EARLY STRESS AND ADOLESCENT CARDIOVASCULAR HEALTH

CAREER: THE EFFECTS OF PROCESS FACILITATION ON EMOTION REGULATION

COLLABORATIVE RESEARCH: WHAT MAKES A GENERALIST HERBIVORE? THE INTERPLAY BETWEEN TOP-DOWN AND BOTTOM-UP FORCES ON HERBIVORE DIET BREADTH

ENGAGES AMERICORPS MEMBERS IN FULL AND PART-TIME SERVICE TO MEET COMMUNITY NEEDS IN EDUCATION, THE ENVIRONMENT, HEALTH, VETERANS, AND OTHER AREAS

INVESTIGATING THE CHAPERONE ACTIVITY OF NUCLEIC ACIDS

BUILDING A SCIENCE OF EDUCATION: LESSONS LEARNED FROM THE USE OF MODELS FOR RESEARCH AND DEVELOPMENT OF EDUCATIONAL INTERVENTIONS -IMPROVING EDUCATION REQUIRES THE DEVELOPMENT OF SCIENTIFICALLY GROUNDED PROGRAMS, PRACTICES, AND POLICIES. OVER THE PAST SEVERAL DECADES, RESEARCHERS AND EDUCATORS HAVE EMPLOYED A RANGE OF RESEARCH-AND-DEVELOPMENT FRAMEWORKS TO SUPPORT THIS GOAL. ALTHOUGH THESE FRAMEWORKS ARE DESIGNED TO GUIDE THE TRANSLATION OF RESEARCH INTO EFFECTIVE EDUCATIONAL PRACTICE, THEIR IMPLEMENTATION AND IMPACT HAVE VARIED CONSIDERABLY. THIS PROJECT EXAMINES THE STRENGTHS AND LIMITATIONS OF ONE WIDELY USED FRAMEWORK THAT HAS INFORMED THE DEVELOPMENT OF CURRICULA, INTERVENTIONS, PROFESSIONAL LEARNING, AND POLICY. BY ANALYZING HOW THE FRAMEWORK HAS BEEN APPLIED AND THE OUTCOMES ASSOCIATED WITH ITS USE, THE PROJECT WILL IDENTIFY COMMON CHALLENGES, MISINTERPRETATIONS, AND OPPORTUNITIES FOR CONSTRUCTIVE ALTERATION. THE FINDINGS ARE INTENDED TO INFORM FUTURE FRAMEWORK DESIGN, SUPPORTING MORE EFFICIENT, SCIENTIFICALLY VALID, AND SCALABLE EDUCATIONAL SOLUTIONS FOR THE FULL RANGE OF THE NATION'S LEARNERS AND EDUCATORS. THE PROJECT WILL CONDUCT A SYSTEMATIC, REVIEW OF AN EXISTING FRAMEWORK THAT HAS SERVED AS THE FOUNDATION FOR NUMEROUS EDUCATIONAL INITIATIVES OVER THE PAST 25 YEARS. USING A COMBINATION OF LITERATURE SYNTHESIS, INTERVIEWS, AND STRUCTURED STAKEHOLDER ENGAGEMENT, THE RESEARCH TEAM WILL IDENTIFY HOW THE FRAMEWORK HAS BEEN UNDERSTOOD, IMPLEMENTED, AND MODIFIED IN PRACTICE. PARTICULAR ATTENTION WILL BE GIVEN TO HOW THE FRAMEWORK SUPPORTS, OR FAILS TO SUPPORT, THE REALIZATION OF THEORY AND RESEARCH INTO PRACTICAL OUTCOMES. THE STUDY WILL INCLUDE OUTREACH TO CURRICULUM DEVELOPERS, RESEARCHERS, AND PROFESSIONAL LEARNING PROVIDERS TO GATHER INSIGHTS INTO THEIR USE OF FRAMEWORKS, INCLUDING BARRIERS AND ENABLERS TO EFFECTIVE APPLICATION. FINDINGS WILL BE USED TO REFINE THEORETICAL MODELS OF RESEARCH-TO-PRACTICE TRANSLATION AND CONTRIBUTE TO THE DEVELOPMENT OF IMPROVED FRAMEWORKS FOR DESIGNING, IMPLEMENTING, AND EVALUATING EDUCATIONAL INTERVENTIONS. THIS WORK WILL ADVANCE UNDERSTANDING OF HOW TO INTEGRATE RESEARCH ON COGNITION, LEARNING, TEACHING, AND CURRICULUM INTO PRACTICAL TOOLS THAT IMPROVE EDUCATION AT SCALE. THIS PROJECT IS JOINTLY FUNDED BY THE TRANSLATION AND DIFFUSION (TD) PROGRAM THAT SUPPORTS RESEARCH THAT ADVANCES THE SCIENCE OF TRANSLATION AND DIFFUSION BETWEEN RESEARCH AND PRACTICE IN STEM EDUCATION, AND THE DIRECTORATE FOR TECHNOLOGY, INNOVATION, AND PARTNERSHIPS (TIP), WHICH ADVANCES USE-INSPIRED AND TRANSLATIONAL RESEARCH IN ALL FIELDS OF SCIENCE AND ENGINEERING. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

RNAS THAT RESIST DEGRADATION IN THE CELL AND THE MANIPULATION OF RNA STABILITY IN LIVING ORGANISMS

CENTROSOMES AND CYTOSKELETAL MECHANISMS OF BLOOD VESSEL DYSFUNCTION

DEPLOYMENT-FOCUSED DEVELOPMENT OF DEPRESSION TREATMENT FOR VICTIMIZED YOUTH

TARGETING QUADRUPLEX BINDING IN ALS

RACIAL BIASES IN PAIN TREATMENT: TESTS OF PAIN-CARE RECOMMENDATIONS, TREATMENT BIASES, AND RACE PERCEPTION MECHANISMS - PROJECT SUMMARY/ABSTRACT E. PAIGE LLOYD, PHD IS A SOCIAL PSYCHOLOGIST WHOSE ULTIMATE CAREER GOAL IS TO USE HER EXPERTISE IN INTERGROUP RELATIONS TO INVESTIGATE THE SOCIAL PSYCHOLOGICAL UNDERPINNINGS OF HEALTH DISPARITIES AND CREATE INTERVENTIONS THAT REDUCE TREATMENT DISPARITIES AND PROMOTE EQUITABLE CARE. THE RESEARCH SHE PROPOSES TITLED, “RACIAL BIASES IN PAIN TREATMENT: TESTS OF PAIN-CARE RECOMMENDATIONS, TREATMENT BIASES, AND THE MALLEABILITY OF RACE PERCEPTION PROCESSES” ADDRESSES GAPS IN THE LITERATURE, OFFERS PRACTICAL INSIGHTS, AND PROVIDES A PLATFORM FOR DEVELOPMENT. RESEARCH: PAIN IS A PREVALENT AND CONSEQUENTIAL HEALTH CONCERN. HOWEVER, PAIN CARE IS NOT EQUALLY DISTRIBUTED; FOR EXAMPLE, WHITE AMERICANS RECEIVE MORE AGGRESSIVE AND GUIDELINE-DIRECTED PAIN CARE THAN BLACK AMERICANS. ALTHOUGH THERE IS CONSISTENT EVIDENCE OF PAIN CARE DISPARITIES, THERE IS NO WORK INTEGRATING MODELS OF RACE PERCEPTION OR EXPERIMENTALLY EXAMINING THE CONTRIBUTION OF THESE PROCESSES TO PAIN CARE DECISIONS. THE OVERALL OBJECTIVE OF THIS RESEARCH IS TO IDENTIFY AND ATTENUATE PROBLEMATIC RACE-PERCEPTION PROCESSES CONTRIBUTING TO RACIAL BIASES IN PAIN TREATMENT. TO TEST THIS OBJECTIVE, DR. LLOYD WILL PURSUE THE FOLLOWING SPECIFIC AIMS: AIM #1: TO INVESTIGATE THE PRESENCE AND PATTERN OF CLINICIAN BIASES IN PAIN CARE FOR WHITE, BLACK, AND MULTIRACIAL BLACK/WHITE HYPOTHETICAL PATIENTS, AIM #2: TO EXAMINE THE EXTENT TO WHICH PERSON PERCEPTION PROCESSES ARE ASSOCIATED WITH TREATMENT RECOMMENDATIONS FOR HYPOTHETICAL BLACK, WHITE, AND BLACK/WHITE PATIENTS, AIM #3: TO EMPIRICALLY TEST A NOVEL INTERVENTION DESIGNED TO ATTENUATE RACE PERCEPTION BIASES. THREE COMPLEMENTARY STUDIES EMPLOYING VIGNETTE, STANDARDIZED PATIENT, AND INTERVENTION DESIGNS WILL 1) EXAMINE PAIN CARE BIASES ACROSS BLACK, WHITE, AND BLACK/WHITE MULTIRACIAL HYPOTHETICAL PATIENTS, 2) THE RACE PERCEPTION MECHANISMS THAT INFORM TREATMENT RECOMMENDATIONS, AND 3) POTENTIAL SOLUTIONS TO BIASES IN RACE PERCEPTION. TRAINING: THE PROPOSED CAREER DEVELOPMENT PLAN WILL BUILD UPON DR. LLOYD’S PREVIOUS TRAINING WITH THREE TRAINING GOALS: 1) EXPAND MEASUREMENT AND STATISTICAL EXPERTISE TO ENCOMPASS ASSESSMENT OF RACE CATEGORIZATION AND NONVERBAL BIASES, 2) GAIN EXPERTISE IN THE ETHICS, THEORY, AND METHODOLOGIES OF HEALTH SERVICES RESEARCH RELEVANT TO DISPARITIES 3) LEARN ABOUT DEVELOPING AND IMPLEMENTING TRANSLATIONAL INTERVENTIONS. DR. LLOYD AND HER MENTORSHIP TEAM PROPOSE SPECIFIC TRAINING ACTIVITIES, DIDACTIC AND EXPERIENTIAL, THAT WILL ENABLE HER TO GAIN THE SKILLS NECESSARY TO COMPLETE THE PROPOSED RESEARCH AND DEVELOP AS AN INDEPENDENT SCIENTIST. THIS TRAINING WILL BE SUPPORTED BY AN EXPERIENCED AND SUCCESSFUL MULTIDISCIPLINARY TEAM. DR. LLOYD’S INSTITUTION AND DEPARTMENT, THE UNIVERSITY OF DENVER AND THE DEPARTMENT OF PSYCHOLOGY, ARE COMMITTED TO HER SUCCESS AND HAVE PROVIDED EXTENSIVE RESOURCES TO PROMOTE HER PRODUCTIVITY AND TRAINING. THIS AWARD WILL PROVIDE DR. LLOYD WITH THE TRAINING AND PILOT DATA REQUIRED TO SEEK R01 FUNDING, BECOME A NATIONALLY-RECOGNIZED INDEPENDENT INVESTIGATOR, AND MAKE SCIENTIFIC CONTRIBUTIONS THAT PROMOTE EQUITABLE CARE.

CAREER: DEVELOPMENT OF CATALYTIC, SULFUR-FREE CHAIN TRANSFER AGENTS TO IMPROVE MECHANICAL AND MATERIAL PERFORMANCE OF CROSSLINKED PHOTOPOLYMERS -WITH FUNDING FROM THE CHEMICAL CATALYSIS (CAT) AND MACROMOLECULAR, SUPRAMOLECULAR, AND NANOCHEMISTRY (MSN) PROGRAMS OF THE DIVISION OF CHEMISTRY (CHE), AND THE POLYMER PROGRAM OF DIVISION OF MATERIALS RESEARCH (DMR), BRADY WORRELL OF THE UNIVERSITY OF DENVER WILL DEVELOP A CATALYTIC, SULFUR-FREE CHAIN TRANSFER AGENT (CTA) FOR EFFICIENTLY CREATING PHOTOPOLYMERS. AN IMPORTANT SUBSET OF PLASTICS IS PHOTOPOLYMER, OR CROSSLINKED MATERIALS CREATED WITH LIGHT. PHOTOPOLYMERS MAKE UP THE POLYMER COMPONENT OF MATERIALS COMMONLY USED IN 3D PRINTING, DENTISTRY, AND BIOMATERIALS, HOWEVER, ONLY A LIMITED WINDOW OF MECHANICAL PROPERTIES CAN EASILY BE ACCESSED FROM AVAILABLE CHEMICAL FEEDSTOCKS. IN THE WORK PROPOSED HERE, DR. WORRELL AND HIS TEAM WILL CREATE CATALYSTS THAT HAVE THE POTENTIAL TO SIGNIFICANTLY ALTER THE MECHANICAL PROPERTIES OF PHOTOPOLYMERS WHILE KEEPING >99% OF THE CHEMICAL COMPOSITION THE SAME. DR. WORRELL WILL ALSO ESTABLISH AND RUN THE SUMMER HIGH SCHOOL INTERNSHIPS: NEW EXPERIMENTALISTS AT UNIVERSITY OF DENVER (SHINE @ DU) PROGRAM, WHICH AIMS TO OFFER LOCAL, UNDER-REPRESENTED HIGH SCHOOL STUDENTS REAL-WORLD RESEARCH EXPERIENCES HOSTED IN THE DEPARTMENT OF CHEMISTRY & BIOCHEMISTRY. AN UNDERGRADUATE LED ONLINE JOURNAL DETAILING SCALABLE, SIMPLE, AND INEXPENSIVE PREPARATIONS OF ORGANIC POLYMERS IS TO BE ESTABLISHED AS PART OF THIS CAREER AWARD EFFORT. THE MATERIALS GENERATED BY PHOTOPOLYMERIZATION ARE INHERENTLY HIGHLY CROSSLINKED AND SUFFER FROM SIGNIFICANT SHRINKAGE STRESS, ARE OFTEN BRITTLE, AND HAVE A LIMITED RANGE OF MATERIAL PROPERTIES. VARIOUS CLASSES OF CHAIN TRANSFER AGENTS (CTAS) HAVE BEEN INVESTIGATED AND DEVELOPED TO REDUCE THE CROSSLINKING DENSITY OF PHOTOPOLYMERS. ALTHOUGH CTAS ARE SUCCESSFUL IN MANIPULATING THE MECHANICAL PROPERTIES OF PHOTOPOLYMERS, THEY ARE REQUIRED IN HIGH LOADINGS (UP TO 20 WT% OF TOTAL FORMULATION) AND FREQUENTLY CONTAIN SULFUR WHICH IS MALODOROUS AND CAN CREATE UNSTABLE FORMULATIONS. DR. WORRELL AND HIS RESEARCH TEAM ARE DEVELOPING A CATALYTIC, SULFUR-FREE CTA THAT CAN BE ADDED IN PPM QUANTITIES TO EXISTING COMMERCIAL MONOMER FEEDSTOCKS TO CREATE PHOTOPOLYMERS SIMILAR TO THOSE PREPARED USING TRADITIONAL CTAS, BUT AT 10,000X LOWER LOADINGS. SEVERAL ANALOGS OF THE MACROCYCLIC COBALT(II) CATALYST WILL BE EXPLORED TO IMPROVE RESIN SOLUBILITY AND VARIOUS LIGANDS WILL BE SCREENED IN A HIGH-THROUGHPUT FASHION IN THE SEARCH FOR POTENT CATALYST:LIGAND COMBINATIONS. THESE CATALYTIC CTAS WILL BE TESTED IN COMMERCIAL 3D PRINTING RESINS AND LIQUID CRYSTAL ELASTOMERS TO NARROW AND REDUCE THE GLASS TRANSITION TEMPERATURE, REDUCE STORAGE MODULUS, AND ALTER OTHER PERTINENT MECHANICAL PROPERTIES. 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.

NATIONAL CENTER FOR EDUCATION RESEARCH

GENERATION OF CELL-BASED AND ANIMAL-BASED IMAGING SYSTEMS FOR MONITORING SYNAPTIC

MATERIALS RESEARCH OF HIGH RESOLUTION GAMMA RAY DETECTORS FOR NONPROLIFERATION APPLICATIONS

NEUROMUSCULAR NEUTRAL ZONES IN HUMANS: A NEW METHOD TO ASSESS SPINAL STABILITY

PHOSPHOLIPASE D REGULATION OF EXOSOME SECRETION -WITH THE SUPPORT OF THE CHEMISTRY OF LIFE PROCESSES PROGRAM IN THE DIVISION OF CHEMISTRY, MICHELLE KNOWLES OF THE UNIVERSITY OF DENVER IS STUDYING HOW CELLS CONTROL THEIR COMMUNICATION WITH ONE ANOTHER. ONE WAY THAT CELLS COMMUNICATE IS THROUGH THE SECRETION OF NANOSCOPIC PACKETS CALLED ?EXOSOMES.? EXOSOMES ARE LIPID-COATED CONTAINERS THAT CARRY MOLECULES AND TRAVEL THROUGH THE BODY, WHERE THEY ARE TAKEN UP BY OTHER CELLS. EXOSOMES CAN ALTER THE FUNCTION OF OTHER CELLS, FOR BETTER OR WORSE. THE FACTORS THAT CONTROL HOW CELLS MAKE EXOSOMES AND THEIR RELEASE ARE NOT FULLY UNDERSTOOD. THE RESEARCH SUPPORTED BY THIS AWARD WILL FOCUS ON THE LIPID-MODIFYING PROTEIN, PHOSPHOLIPASE D (PLD), AN ENZYME, AND ON PHOSPHATIDIC ACID (PA), WHICH IS A LIPID WHOSE PRODUCTION IS CATALYZED BY PLD. PA CAN ALTER THE SHAPES OF MEMBRANES AND ACTS AS A SIGNALING MOLECULE. THE ROLE OF PLD AND PA IN THE FORMATION OF EXOSOMES AND THEIR RELEASE WILL BE INVESTIGATED. BEYOND GENERATING NEW KNOWLEDGE ABOUT EXOSOMES, THE PROJECT WILL CREATE OPPORTUNITIES FOR GRADUATE AND UNDERGRADUATE STUDENTS TO LEARN HOW TO USE STATE OF THE ART TECHNOLOGY TO ADDRESS PROBLEMS AT THE FOREFRONT OF CELL COMMUNICATION. DRS. KNOWLES AND DINAH LOERKE (UNIVERSITY OF DENVER) WILL DEVELOP A PEER MENTORING PROGRAM FOR GRADUATE STUDENTS. THE RESULTS OF SCIENTIFIC AND BROADER IMPACT ACTIVITIES WILL BE PRESENTED AT CONFERENCES AND PUBLISHED TO ALLOW OTHERS TO BUILD UPON THE FOUNDATIONAL KNOWLEDGE OBTAINED ABOUT CELLULAR REGULATION AND STUDENT MENTORSHIP. PHOSPHOLIPASE D AND PHOSPHOLIPASE A (PLD AND PA) COULD BE INVOLVED IN THE FORMATION OF EXOSOMES AND/OR IN THE RELEASE PROCESS ITSELF. BOTH STEPS REQUIRE HIGHLY CURVED MEMBRANES. IN THIS RESEARCH PROJECT, THE PRESENCE OF PLD AND THE FORMATION OF PA WILL BE MAPPED IN SPACE AND TIME DURING EXOSOME SECRETION. QUANTITATIVE FLUORESCENCE MICROSCOPY APPROACHES WILL BE USED IN CONJUNCTION WITH STANDARD BIOCHEMICAL METHODS TO ASSESS THE NUMBER OF EXOSOMES AND THE FREQUENCY WITH WHICH THEY ARE RELEASED FROM CELLS. THE FORMATION, TRAFFICKING AND FUSION STAGES OF THE EXOSOME LIFECYCLE WILL BE ASSESSED IN LIVE CELLS. THE ACTIVITY AND PRESENCE OF PLD WILL BE ALTERED TO DETERMINE WHEN AND WHERE PLD AND PHOSPHATIDIC ACID ARE REQUIRED. THIS PROJECT HAS THE POTENTIAL FOR FAR-REACHING SCIENTIFIC IMPACT; SPECIFICALLY, BY DEMONSTRATING THE USE OF BIOPHYSICAL TOOLS/CHEMICAL BIOLOGY TO HELP TO ELUCIDATE IMPORTANT MECHANISMS OF CELLULAR COMMUNICATION. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

THE AWARD APPROVES FUNDING FOR THE FY2022 NATIONAL SERVICE AND CIVIC ENGAGEMENT RESEARCH FUNDING OPPORTUNITY DESCRIBED IN THE APPROVED PROGRAM NARRATIVE AND BUDGET.THE 2022 REQUIRED MATCH IS 0%. THIS AWARD ALSO FORWARD FUNDS $105,818 FOR THE 2023-24 PROGRAM YEAR.

NEW START CA FOR UNIVERSITY OF DENVER.

LIBRARIANS FOR THE 21ST CENTURY

COMPLEXITY-BUILDING APPROACHES IN PHOTOASSISTED SYNTHESIS OF HETEROCYCLES -WITH THE SUPPORT OF THE CHEMICAL SYNTHESIS PROGRAM IN THE DIVISION OF CHEMISTRY, PROFESSOR ANDREI KUTATELADZE OF UNIVERSITY OF DENVER IS STUDYING THE DEVELOPMENT OF NEW MOLECULAR COMPLEXITY-BUILDING METHODS FOR THE SYNTHESIS OF ORGANIC COMPOUNDS THAT POSSESS POTENTIALLY USEFUL PROPERTIES. THE MAJOR THRUST OF THIS RESEARCH IS BASED ON PHOTOASSISTED APPROACHES, I.E. USING LIGHT AS A READILY AVAILABLE ENERGY SOURCE, ALLOWING FOR RAPID ACCESS TO COMPLEX MOLECULAR ARCHITECTURES. BESIDES THE FUNDAMENTAL IMPORTANCE OF LEARNING ABOUT THE INTERACTIONS OF LIGHT AND MATTER IN THE CONTEXT OF SYNTHETIC CHEMISTRY, THE TARGETED COMPLEX HETEROCYCLES, I.E. MOLECULES THAT CONTAIN NITROGEN, SULFUR, OR OXYGEN ATOMS AS A PART OF A RING, ARE INTENTIONALLY DESIGNED TO RESEMBLE ALKALOIDS, AN IMPORTANT CLASS OF NATURAL PRODUCTS THAT MAY POSSESS USEFUL THERAPEUTIC PROPERTIES. IMPORTANTLY, THIS AWARD WILL ALSO SUPPORT RESEARCH EXPERIENCES FOR UNDERGRADUATE AND GRADUATE STUDENTS, INCLUDING THOSE FROM HISTORICALLY UNDERREPRESENTED GROUPS IN SCIENCE, THEREBY WORKING TOWARD INCLUSIVE EXCELLENCE IN THE FIELD OF ORGANIC CHEMISTRY. THIS RESEARCH AIMS TO FURTHER EXPAND THE SYNTHETIC PHOTOCHEMISTRY TOOLBOX, SPECIFICALLY TO FURTHER DEVELOP EXCITED STATE INTRAMOLECULAR PROTON TRANSFER (ESIPT)-BASED PHOTOASSISTED SYNTHETIC REACTION CASCADES. FOR EXAMPLE, THE KUTATELADZE GROUP IS TARGETING HYDROGEN ATOM TRANSFER (HAT) IN TRIPLET STATES, DESIGNED TO ACHIEVE LARGE STEP-NORMALIZED COMPLEXITY INCREASES IN THE SYNTHESIS OF COMPLEX HETEROCYCLIC MOLECULAR ARCHITECTURES. THIS WORK WILL ALSO INCLUDE A VERTICAL GROWTH IN COMPLEXITY THROUGH POST-PHOTOCHEMICAL TRANSFORMATIONS. REACTION MECHANISMS AND THE STEREOCHEMISTRY OF THESE ESIPT-TRIGGERED CASCADES WILL BE INVESTIGATED TO BETTER UNDERSTAND HOW THESE TRANSFORMATIONS ACHIEVE THEIR STEREO- AND REGIOCHEMICAL OUTCOMES. THE EXPERIMENTAL WORK WILL BE AUGMENTED BY COMPUTATIONS THAT HAVE BEEN DESIGNED TO FACILITATE SOLUTION STRUCTURE ELUCIDATION OF THE COMPLEX HETEROCYCLIC PRODUCTS BY NUCLEAR MAGNETIC RESONANCE (NMR) SPECTROSCOPY. THE NEWLY INTEGRATED MACHINE LEARNING-AUGMENTED DENSITY FUNCTIONAL THEORY (DFT) METHOD FOR FAST AND ACCURATE CALCULATIONS OF THE NMR PARAMETERS WILL BE EXPANDED TO EXPLICITLY ACCOUNT FOR THE EFFECT OF SOLVENTS ON THE PREDICTED SPECTRA. THIS SUB-THEME OF THE PROPOSED RESEARCH IS CRITICAL FOR THE SUCCESS OF THIS PROJECT BECAUSE OF THE STRUCTURAL COMPLEXITY OF THE TARGET MOLECULES. MOREOVER, FURTHER DEVELOPMENT OF THIS METHOD WILL LIKELY HAVE BROADER IMPLICATIONS FOR THE STRUCTURE ELUCIDATION OF COMPLEX ORGANIC MOLECULES, IN GENERAL. 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.

DEVELOPMENTAL VALIDATION OF A HIGH-SPECIFICITY MULTIPLEX ASSAY FOR HUMAN BODY FLUID IDENTIFICATION

COLLABORATIVE RESEARCH: BROADENING PERSPECTIVES ON INNATE IMMUNITY VIA THE RESPONSE OF DIVERSE EUKARYOTES TO A VERSATILE BACTERIAL PATHOGEN -THE INNATE IMMUNE SYSTEM IS THE FIRST LINE OF DEFENSE AGAINST PATHOGENS, ALLOWING CELLS TO RECOGNIZE WHEN THEY ARE INFECTED AND MOUNT RESPONSES. BECAUSE THESE IMMUNE RESPONSES CAN ALSO BE DANGEROUS TO THE CELL, IT IS CRITICAL FOR ORGANISMS TO DISTINGUISH BETWEEN PATHOGEN INFECTION AND COMMONPLACE BACTERIAL EXPOSURE (E.G. TO THE ENVIRONMENTAL MICROBES AROUND US OR TO OUR OWN MICROBIOMES). THIS DISTINCTION IS PARTICULARLY CHALLENGING FOR ORGANISMS THAT EAT BACTERIA, AS THEY CONSTANTLY INHABIT MICROBE-RICH ENVIRONMENTS AND BRING MICROBES INTO THEIR OWN BODIES. THIS PROJECT BRINGS TOGETHER A CROSS-DISCIPLINARY TEAM OF SCIENTISTS TO INVESTIGATE INNATE IMMUNE RESPONSES IN THREE DIFFERENT ORGANISMS THAT EAT BACTERIA: 1) SPONGES, ONE OF THE EARLIEST BRANCHES ON THE ANIMAL TREE OF LIFE; 2) CHOANOFLAGELLATES, THE CLOSEST LIVING RELATIVES OF ANIMALS; AND 3) AMOEBAE, A MORE DISTANT RELATIVE. BECAUSE THESE ORGANISMS SPAN THE EVOLUTIONARY TRANSITION BETWEEN MULTICELLULAR ANIMALS AND THEIR UNICELLULAR COUSINS, SIMILARITIES AMONG THESE ORGANISMS CAN ILLUMINATE THE ORIGINS OF ANIMAL INNATE IMMUNE SYSTEMS, AS WELL AS REVEAL NOVEL STRATEGIES FOR ANTIBACTERIAL DEFENSE. OUTREACH COMPONENTS OF THIS PROJECT INCLUDE A FOUR-WEEK, SUMMER, PRE-COLLEGE PROGRAM FOR STUDENTS FROM URBAN, PUBLIC, PITTSBURGH HIGH SCHOOLS. STUDENTS WILL CONDUCT HANDS-ON EXPERIMENTS INVESTIGATING SPONGE IMMUNE RESPONSES TO BACTERIA, WHICH THEY WILL PRESENT AT THEIR SCHOOLS AND TO THE PUBLIC AT THE CARNEGIE SCIENCE CENTER. THIS PROJECT WILL TEST THE HYPOTHESIS THAT ORGANISMS WITH HIGH-LEVELS OF MICROBIAL EXPOSURE MAY DISPROPORTIONATELY RELY ON ?EFFECTOR-TRIGGERED IMMUNITY? (ETI) TO MONITOR FOR PATHOGEN ACTIVITY. THE PROPOSED APPROACH IS TO USE THE VERSATILE PATHOGEN LEGIONELLA PNEUMOPHILA TO ELICIT ETI IN THREE SPECIES SELECTED FOR THEIR PHYLOGENETIC POSITION AND LIFESTYLE - AN AMOEBA, A CHOANOFLAGELLATE, AND A SPONGE. L. PNEUMOPHILA IS A PATHOGEN THAT CAN INFECT DIVERSE PROTISTS AND HUMANS BY INJECTING BACTERIAL EFFECTOR PROTEINS INTO HOST CELLS. THIS PATHOGEN THEREFORE ENABLES THE USE OF THE SAME BACTERIAL STRAINS AND SPECIES FOR PARALLEL INVESTIGATIONS OF HOST IMMUNE RESPONSES ACROSS DIVERGED HOST SPECIES. WE HAVE RECENTLY ESTABLISHED A L. PNEUMOPHILA INFECTION MODEL FOR SPONGES. HERE, WE WILL CHARACTERIZE THE INFECTION MODALITIES, IMMUNE CELL TYPES, AND CELLULAR PATHWAYS INVOLVED IN THESE INFECTIONS. WE WILL ALSO ATTEMPT TO EXTEND THIS INFECTION MODEL TO CHOANOFLAGELLATES (IN ADDITION TO THE WELL-ESTABLISHED AMOEBA MODEL) AND USE PARALLEL, UNBIASED APPROACHES TO ASSESS IF THESE ORGANISMS ELICIT ETI IN RESPONSE TO L. PNEUMOPHILA?S GLOBAL TRANSLATION INHIBITION IN HOST 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

THE EVOLUTION OF LEARNING STRATEGIES AS INDICATORS OF INTERVENTION EFFICACY

CAREER: ELECTRONS, PHONONS, AND MAGNONS IN NANOSTRUCTURES AND NOVEL MATERIALS

BEYOND REWARD: APPROACH & AVOIDANCE MOTIVATION GENERATE FUNCTIONAL CONTEXTS FOR COGNITIVE CONTROL & ADAPTIVE MEMORY

COLLABORATIVE RESEARCH: SPIN CURRENTS AND SPIN-ORBIT TORQUES IN SINGLE LAYER MAGNETIC SYSTEMS

IMPACT OF VICTIM OFFENDER DIALOGUE ON VICTIMS OF SERIOUS CRIMES: A LONGITUDINAL COHORT-CONTROL STUDY

CAREER: UNLOCKING "FORBIDDEN" OPTICAL TRANSITIONS IN NANOSTRUCTURES USING LIGHT WITH ORBITAL ANGULAR MOMENTUM

CAREER: NOVEL SPINTRONICS DEVICES BASED ON SYMMETRY-BROKEN SYSTEMS

CAREER: HOW DO THERMOPHILIC PROTEINS WITHSTAND HIGH TEMPERATURE?

CAREER: BIOSENSOR DEVELOPMENT FOR PROBING NANOSCALE TOPOLOGY IN NEUROTRANSMISSION

MRI: ACQUISITION OF A BIPLANE FLUOROSCOPY SYSTEM FOR DYNAMIC IMAGING OF IN-VIVO HUMAN MOTION

CO-EVOLUTION OF THE OPIOID/ORPHANIN GENE FAMILY AND COGNATE RECEPTOR GENE FAMILIES

CPS: TTP OPTION: SYNERGY: COLLABORATIVE RESEARCH: DEPENDABLE MULTI-ROBOT COOPERATIVE TASKING IN UNCERTAIN AND DYNAMIC ENVIRONMENTS

SMALL GROUP READING INTERVENTION TO SUPPORT CHILDREN WITH PERVASIVE LEARNING AND ATTENTION NEEDS (RISC-PLAN) IN THE UPPER ELEMENTARY GRADES

LIBRARIANS FOR THE 21ST CENTURY

BLOWS TO THE HEAD AND STRANGULATION ARE DREADFULLY COMMON AMONG WOMEN VICTIMIZED BY INTIMATE PARTNERS, ACCORDING TO DOZENS OF RESEARCH STUDIES. UNFORTUNATELY, RESEARCH ON THE IMPACT OF BRAIN INJURY (BI) SERVICES ON DOMESTIC VIOLENCE (DV) VICTIMS IN THE CRIMINAL JUSTICE SYSTEM (CJS) IS WOEFULLY LACKING, LEAVING JURISDICTIONS WITH LITTLE EMPIRICAL EVIDENCE TO GUIDE POLICY AND PRACTICE. AT A TIME WHEN PRACTICE REGARDING IPV AND BI SCREENING IS RAPIDLY DEVELOPING, A GOAL IS TO USE RESEARCH TO INFORM ACTIONS TAKEN AFTER THE SCREENING THAT PROMOTE JUSTICE AND ENHANCE CRIMINAL JUSTICE OUTCOMES FOR DV VICTIMS WITH BIS. WITH CRIMINAL JUSTICE AND COMMUNITY-BASED PARTNERS, THIS STUDY WILL CARRY OUT A RANDOMIZED CONTROL TRIAL (RCT) TO TEST THE IMPACT OF A COMMUNITY-COORDINATED RESPONSE (CCR) TO BRAIN INJURY SERVICES OUTREACH. THE CATCHMENT AREA HAS A WELL-ESTABLISHED CCR THROUGH WHICH VICTIMS IN DV CASES HAVE ACCESS TO SYSTEM- AND COMMUNITY-BASED VICTIM ADVOCACY. BOTH ADMINISTRATIVE DATA (N=800 CASES) AND VICTIM INTERVIEWS (N=250) WILL BE USED TO ASSESS IMPACTS, INCLUDING CRIMINAL CASE OUTCOMES AS WELL AS VICTIM ENGAGEMENT, WELLBEING, AND REVICTIMIZATION (BASELINE, 3 AND 6 MONTHS). THE STUDY WILL ALSO IDENTIFY FOR WHOM AND UNDER WHAT CONDITIONS OUTREACH FOR BI SERVICES HAS THE MOST SIGNIFICANT IMPACT. THE RESULTING DATASET WILL TEST FOUR STUDY HYPOTHESES AND ADDRESS CRITICAL QUESTIONS ABOUT THE EFFECTIVENESS OF INTEGRATING BI SERVICES INTO CCRS ON CRIMINAL JUSTICE CASE OUTCOMES, VICTIM ENGAGEMENT, WELLBEING, AND REVICTIMIZATION. THE CURRENT STUDY IS DESIGNED TO INFORM NATIONAL POLICY AND PRACTICE TO PROMOTE JUSTICE FOR VICTIMS OF CRIME AND ENHANCE CRIMINAL JUSTICE RESPONSES TO DV FOR VICTIMS WITH BRAIN INJURIES. FINDINGS WILL BE DISSEMINATED WIDELY TO RESEARCHERS, PRACTITIONERS, POLICYMAKERS, AND SURVIVORS USING VARIOUS MEANS (VIRTUAL AND IN-PERSON MODES). DELIVERABLES INCLUDE SCHOLARLY PRODUCTS (INCLUDING PUBLISHED, PEER-REVIEWED ACADEMIC JOURNAL ARTICLES AND CONFERENCE PRESENTATIONS), A FINAL RESEARCH REPORT AND STUDY DATA THAT WILL BE ARCHIVED AT NACJD, AS WELL AS SOCIAL MEDIA POSTS, WEBINARS, AND OTHER WEB-BASED RESOURCES (E.G., BLOG POSTS, TED TALKS), AND SURVIVOR-FOCUSED MATERIALS. CA/NCF

CAREER: THE INCLUSIVE GLOBAL LEADERSHIP INITIATIVE

GOALI: MODELING OF NEXT GENERATION METAL-FREE FRICTIONLESS MATERIALS FOR THE PREVENTION OF THERMAL-MECHANICAL INSTABILITIES

ENABLING MAGNETISM CONTROL BY THE ELECTRICAL TRIGGERING OF METAL-INSULATOR TRANSITION

FINANCIAL ASSISTANCE FOR COUNTERING VIOLENT EXTREMISM

HELPING GUARDIANS NAVIGATE YOUTH SUICIDE RISK: DEVELOPMENT AND PILOTING OF A BRIEF DIGITAL INTERVENTION - PROJECT SUMMARY YOUTH SUICIDE IS A SIGNIFICANT GLOBAL PUBLIC HEALTH CONCERN, WITH EVIDENCE SUGGESTING A STAGGERING INCREASE OVER THE PAST DECADE, PARTICULARLY AMONG PRE- AND EARLY ADOLESCENTS. CONCURRENTLY, THE WIDESPREAD FREQUENT USE OF SOCIAL MEDIA HAS RESHAPED THE LIVES OF YOUTH AND CREATED SUBSTANTIAL OPPORTUNITY TO HARNESS THEIR DIGITAL FOOTPRINTS TO ENHANCE SUICIDE RISK DETECTION ON A POPULATION-WIDE SCALE. SUBSCRIPTION-BASED DIGITAL MONITORING APPS HAVE EMERGED WITH THE GOAL OF HARNESSING ADVANCEMENTS IN ARTIFICIAL INTELLIGENCE TO IDENTIFY SUICIDE- RELATED CONTENT SHARED OR ACCESSED, AND TO PROMPTLY ALERT PARENTS TO THEIR CHILD’S POTENTIAL SITBS. THESE DIGITAL SUICIDE RISK ALERTS HAVE THE POTENTIAL TO MITIGATE CHILD SITBS BY AUGMENTING THE IDENTIFICATION OF AT-RISK YOUTH, THEREBY FACILITATING PREVENTION EFFORTS. HOWEVER, ALERTING PARENTS TO POTENTIAL SUICIDE RISK WITHOUT EQUIPPING THEM WITH THE SKILLS NECESSARY TO RESPOND EFFECTIVELY COULD INADVERTENTLY EXACERBATE YOUTH RISK. THIS R34 APPLICATION PROPOSES TO DEVELOP AND TEST A DIGITAL SINGLE SESSION INTERVENTION (SSI) FOR PARENTS OF PRE- AND EARLY ADOLESCENTS TARGETING PARENTAL EMOTION REGULATION, VALIDATION, AND SUICIDE-SPECIFIC MONITORING. THIS INTERVENTION SEEKS TO SUPPORT PARENTS IN RESPONDING EFFECTIVELY TO DIGITAL MONITORING APP-GENERATED SUICIDE RISK ALERTS, THEREBY DECREASING CHILD SITB RISK. THIS PROJECT AIMS TO FIRST DEVELOP AND ITERATIVELY REFINE AN SSI PAIRED WITH A JUST-IN-TIME DIGITAL INTERVENTION (JIT) TRIGGERED BY THE RECEIPT OF SUICIDE RISK ALERTS RECEIVED THROUGH A DIGITAL MONITORING APP. IN PHASE 1, WE WILL ENGAGE N=20 PARENTS WHO USE THE DIGITAL MONITORING APP TO CO-CREATE AND REFINE THE SSI AND SSI+JIT INTERVENTION PROTOTYPES. IN PHASE 2, WE WILL CONDUCT AN OPEN TRIAL WITH N=15 PARENTS OF YOUTH (AGES 10-15) SCREENED AS AT-RISK TO INFORM FEASIBILITY, ACCEPTABILITY, AND FINAL INTERVENTION MODIFICATIONS. IN PHASE 3, WE WILL CONDUCT A PILOT RCT AMONG N=99 PARENTS OF YOUTH (AGES 10-15) SCREENED AS AT-RISK TO TEST THE PRELIMINARY EFFECTIVENESS OF THE SSI AND SSI+JIT INTERVENTIONS AS COMPARED TO ENHANCED USUAL CARE (EUC) ON HYPOTHESIZED PARENT-FOCUSED TARGETS. WE WILL ASSESS INTERVENTION TARGETS AND OUTCOMES VIA SELF-REPORT SURVEYS FROM PARENT-CHILD DYADS AT 1-, 3-, AND 6-MONTH FOLLOW-UP. WE HYPOTHESIZE THAT PARENTS IN THE SSI+JIT WILL EVIDENCE THE GREATEST USE OF TARGETED SKILLS, FOLLOWED BY PARENTS IN THE SSI-ONLY AND THEN EUC GROUPS. WE ALSO HYPOTHESIZE THAT CHILDREN OF PARENTS IN THE SSI+JIT AND SSI-ONLY WILL REPORT LESS SI AT FOLLOW-UP COMPARED TO CHILDREN OF PARENTS IN THE EUC CONDITION. FINDINGS FROM THIS R34 PROPOSAL WILL INFORM THE FEASIBILITY, ACCEPTABILITY, AND INITIAL EFFICACY OF A SSI DESIGNED TO REDUCE CHILD SITB RISK THROUGH EARLY PARENTAL INTERVENTION. THIS WORK HAS IMPORTANT IMPLICATIONS FOR THE USE OF BRIEF DIGITAL INTERVENTIONS TO PREVENT SUICIDE AMONG AT-RISK YOUTH THAT MAY BE SCALED AND ADAPTED FOR A BROAD RANGE OF SETTINGS (E.G., EMERGENCY DEPARTMENTS, PEDIATRICIAN’S OFFICES, SCHOOLS) SERVING PARENTS AND CHILDREN.

COMPLEXITY-BUILDING APPROACHES IN PHOTOASSISTED SYNTHESIS OF HETEROCYCLES

PROGRESS TOWARDS UNDERSTANDING NEUROTRANSMISSION: TEMPORAL MAPPING OF PHOSPHOLIPASE D ACTIVITY IN EXOCYTOSIS

CAREER: MULTIPLEXING BIOMEDICAL SENSOR SYSTEMS FOR AUTOMATED DIAGNOSIS BY MACHINE LEARNING -THE DIAGNOSIS OF HUMAN HEALTH CONDITIONS HAS ALWAYS BEEN CHALLENGING DUE TO THE COMPLEXITY OF HUMAN PHYSIOLOGY. THEREFORE, MULTIPLE TESTS TO IDENTIFY MULTIPLE BIOMARKERS ARE OFTEN REQUIRED FOR DIAGNOSIS AND PROGNOSIS OF DISEASES. THIS PROCESS TAKES TIME AND RESOURCES, INCLUDING WELL-TRAINED HEALTH PROVIDERS, LABORATORY TECHNICIANS TO RUN THE TESTS, AND CLINICIANS TO INTERPRET THE RESULTS. TO ADDRESS THIS CONCERN, THIS PROJECT WILL INVESTIGATE MULTIPLEXED BIOMEDICAL SENSORS THAT ARE CAPABLE OF ULTRASENSITIVE DETECTION OF MULTIPLE BIOMARKERS SIMULTANEOUSLY SO THAT HEALTH CONCERNS COULD BE IDENTIFIED IN THEIR EARLY STAGES. THE PROJECT WILL ALSO INVESTIGATE AUTOMATED DATA ANALYTICS AND DIAGNOSIS SYSTEMS BY UTILIZING MACHINE LEARNING ALGORITHMS FOR AN ACCURATE AND UNBIASED INTERPRETATION OF THE TEST RESULTS. FINALLY, THIS PROJECT INTEGRATES RESEARCH WITH EDUCATIONAL AND OUTREACH INITIATIVES DESIGNED TO EXCITE K-12 STUDENTS ABOUT STEM OPPORTUNITIES AND TRAIN UNDERGRADUATE AND GRADUATE STUDENTS IN THE AREA OF BIOSENSORS, MACHINE LEARNING, AND NANOTECHNOLOGY FOR BIOMEDICAL STEWARDSHIP. THIS CAREER PROJECT IS TO DEVELOP INTEGRATIVE BIOMEDICAL SENSORS FOR AUTOMATED DIAGNOSIS BY SYNERGISTIC INTEGRATION OF NEW SENSING PLATFORMS FOR BIOMARKER DETECTION, AS WELL AS MACHINE LEARNING ALGORITHMS FOR ACCURATE AND UNBIASED INTERPRETATION OF THE RESULTS. FOUR MAIN AIMS WILL BE PURSUED: (1) STUDY AND FABRICATE PLEXCIMONIC STRUCTURES, WHERE PLEXCIMONS ARE PLASMON-EXCITON-PLASMON HYBRID SYSTEMS EXHIBITING NEW ENERGY STATES THAT ARE SUITABLE FOR MULTIPLEXED SENSING, (2) DEVELOP A MULTIPLEXED SENSING SYSTEM BY EXPLORING PLEXCIMONIC STRUCTURES WITH MULTIPLE BIOMARKERS, (3) DEVELOP ALGORITHMS THAT CORRELATE THE SENSOR RESULTS FOR MULTIPLE BIOMARKERS, AND (4) CREATE AN ADVANCED UNDERSTANDING OF LIGHT-MATTER INTERACTIONS IN PLEXCIMONIC STRUCTURES AND MACHINE LEARNING IN MEDICAL APPLICATIONS. THIS APPROACH OFFERS ADVANTAGES OVER THE CONVENTIONAL METHODS SUCH AS PLASMONIC SENSORS AND ELISA THAT DO NOT PROVIDE SENSITIVITY AND MULTIPLEXING SIMULTANEOUSLY. THE TECHNOLOGY WILL ALSO ADVANCE POINT-OF-CARE SYSTEMS THROUGH AUTOMATED DIAGNOSIS. THE EDUCATIONAL COMPONENT OF THIS CAREER PLAN AIMS TO DEVELOP AN EDUCATION PROGRAM FOR LIGHT-MATTER INTERACTIONS FOR NANO-ENGINEERED STRUCTURES. THIS EFFORT WILL ENERGIZE STUDENT LEARNING BY USING NANOSTRUCTURES IN LABORATORIES, DEMONSTRATE A MULTIDISCIPLINARY PERSPECTIVE OF BIOMEDICAL SENSORS, AND STIMULATE STUDENTS' COLLABORATIVE LEARNING THROUGH BIOSENSOR PROJECTS. THIS ACTIVITY WILL ENHANCE RECRUITMENT AND RETENTION OF UNDERREPRESENTED GROUPS IN STEM FIELDS AND WILL MOTIVATE STUDENTS TOWARDS LIFELONG LEARNING AND CAREERS RELATED TO BIOMEDICAL DISCIPLINES, COMPUTER SCIENCE, AND ENGINEERING IN GENERAL. 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.

HEAT, CHARGE, AND SPIN: THERMAL SPINTRONICS IN FERROMAGNETIC FILMS AND NANOSTRUCTURES

THE ALCOHOL AND OTHER DRUGS EDUCATION PROGRAM (ADEP) FOR SOCIAL WORK FACULTY

SHB: LARGE: COLLABORATIVE RESEARCH: COMPANIONBOTS FOR PROACTIVE THERAPEUTIC DIALOG ON DEPRESSION

THE IMPACT OF A FORENSIC COLLABORATIVE FOR OLDER ADULTS ON CRIMINAL JUSTICE AND VICTIM OUTCOMES: A RANDOMIZED-CONTROL, LONGITUDINAL DESIGN

TOWARDS AN INTEGRATIVE MODEL OF CELL ADHESION AND SELF-RECOGNITION IN SPONGE (PORIFERA) TISSUES

COLLABORATIVE RESEARCH: ORCC: INTEGRATING LEAF METABOLOMICS AND TREE DEMOGRAPHIC MODELS TO UNDERSTAND CLIMATE CHANGE IMPACTS ON FORESTS IN THE ROCKIES AND SMOKIES -THE HEALTH OF U.S. FORESTS IS OF PARAMOUNT IMPORTANCE FOR ECONOMIC SECURITY, BUT RAPID ENVIRONMENTAL CHANGE IS PLACING UNPRECEDENTED STRESSES ON TREES THAT MAY LEAD TO CATASTROPHIC FOREST LOSS. FORECASTING THESE CHANGES IS A PRIORITY FOR MANAGEMENT, BUT SCIENTISTS AND MANAGERS ALIKE REQUIRE NEW TOOLS FOR UNDERSTANDING HOW NEAR-TERM STRESSES INFLUENCE TREE SURVIVAL, A PROCESS OFTEN DELAYED BY MONTHS OR YEARS. IN THIS INTERDISCIPLINARY PROJECT, ECOLOGISTS, BIOCHEMISTS, AND MODELERS ARE APPLYING A NEW LABORATORY TECHNOLOGY RELATED TO CHEMICAL FINGERPRINTING TO UNDERSTAND HOW IMMEDIATE CHANGES IN LEAF CHEMISTRY MAY DETERMINE WHETHER A TREE LIVES OR DIES IN RESPONSE TO DROUGHT. THIS APPROACH IS NOVEL BECAUSE IT ?PEEKS INSIDE? A LEAF TO MEASURE HOW IT HANDLES STRESS IN REAL-TIME, BUT PERFORMED IN NATURAL FOREST SETTINGS TO TAKE ADVANTAGE OF LONG-TERM DATASETS OF TREE GROWTH AND SURVIVAL IN TWO ICONIC U.S. NATIONAL PARKS. IN THIS WAY, THIS PROJECT IS DEVELOPING EARLY-WARNING MARKERS OF TREE MORTALITY RISK, WITH THE ULTIMATE GOAL OF PROVIDING ACCURATE FORECASTS OF FOREST HEALTH UNDER CHANGING ENVIRONMENTAL CONDITIONS. RESEARCHERS ARE TESTING NEW HYPOTHESES THAT PROVIDE A MECHANISTIC FRAMEWORK FOR LINKING STRESS-RELATED METABOLOMICS TO WHOLE-PLANT PHYSIOLOGY AND FOREST DEMOGRAPHY. THE MAIN HYPOTHESIS IS THAT ENERGETIC CONSTRAINTS INDUCED BY LIGHT COMPETITION SIGNIFICANTLY ALTER THE LEAF METABOLOME COMPOSITION OF DROUGHT-STRESSED SAPLINGS TOWARD THOSE COMPOUNDS THAT MAXIMIZE THE EFFICACY OF ANTIOXIDANT AND OSMOREGULANT ACTIVITY AT A RELATIVELY LOW COST OF BIOSYNTHESIS. SUCH CONSTRAINTS POTENTIALLY DECOUPLE GROWTH-SURVIVAL AND GROWTH-FECUNDITY RELATIONSHIPS IN FOREST DEMOGRAPHY. RESEARCHERS WILL FIRST COUPLE MEASUREMENTS OF LEAF PHYSIOLOGY AND METABOLOME COMPOSITION IN CONTROLLED DROUGHT-RESPONSE EXPERIMENTS OF EIGHT DIFFERENT TREE SPECIES TO THAT OF THE SAME SPECIES ALONG MOISTURE GRADIENTS IN GREAT SMOKY MOUNTAIN AND ROCKY MOUNTAIN NATIONAL PARKS. FOREST SIMULATION MODELS WILL INCORPORATE EFFECTS OF DROUGHT AND LIGHT ON TREE RECRUITMENT, GROWTH, AND SURVIVAL, AND INTEGRATE DEMOGRAPHIC OUTCOMES CONVEYED BY METABOLOMICS PROFILING. A TRANSFORMATIVE ASPECT OF THIS ACTIVITY IS THE IDENTIFICATION OF ?STASIS? POPULATIONS THAT ARE DEMOGRAPHICALLY STABLE BUT EXPERIENCING SIGNIFICANT DROUGHT STRESS. SUCH POPULATIONS INDICATE DISEQUILIBRIAL DYNAMICS IN SPECIES DISTRIBUTION MODELS, AND PROVIDE CRITICAL INFORMATION FOR FORECASTING FUTURE FOREST COMPOSITION. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

TRANSACTIONAL FAMILY PROCESSES SUPPORTING FATHER INVOLVEMENT AND CHILD SOCIO-EMOTIONAL WELLBEING

EMERGENT GAZE PERCEPTION IN AUTISM SPECTRUM DISORDER

QUANTUM STIMULATED RAMAN SPECTROSCOPY AND SENSING -THE GOAL OF THIS PROPOSAL IS TO DEMONSTRATE A NEW SENSING TECHNIQUE CALLED ?QUANTUM STIMULATED RAMAN SPECTROSCOPY? (QSRS) THAT IS EXTREMELY SENSITIVE TO VIBRATIONAL RESONANCES IN MATERIALS, PROVIDING A UNIQUE ?FINGERPRINT? THAT CAN DISTINGUISH MATERIALS. THE KEY INNOVATION BEHIND QSRS IS THE USE OF ENTANGLED PHOTONS (SINGLE LIGHT PARTICLES) AS THE PROBING SOURCE; CALCULATIONS SUGGEST THAT THE CORRELATIONS FROM ENTANGLEMENT MAKES QSRS MORE THAN A TRILLION TIMES MORE SENSITIVE THAN CLASSICAL MEASUREMENTS. IN ADDITION TO THIS UNPRECEDENTED ENHANCEMENT, QSRS MEASUREMENTS ARE SENSITIVE TO QUANTUM EXCITATIONS, LIKE A SINGLE VIBRATIONAL MODE OR EXCITED ELECTRON. IN THE PROPOSED WORK, THE TEAM WILL BUILD THE FIRST QSRS SETUP, TEST AND OPTIMIZE IT WITH A VARIETY OF MATERIALS, AND THEN USE QSRS TO EXCITE, MEASURE, AND SENSE SINGLE VIBRATIONS AND ELECTRONS. THIS NEW QUANTUM SENSITIVITY ENABLES NON-DESTRUCTIVE COMPOSITIONAL SENSING THAT HAS POTENTIAL TO BE APPLIED IN EXCITING WAYS, INCLUDING BIOLOGICAL IMAGING FOR CANCER SCREENING, CHEMICAL AND WEAPONS DETECTION, AND COMPUTER CHIP VALIDATION AND TESTING. QSRS IS INSPIRED BY THE ORDERS-OF-MAGNITUDE CROSS-SECTION ADVANTAGE ACHIEVED FROM ENTANGLED PHOTON CORRELATIONS IN ENTANGLED TWO PHOTON ABSORPTION; BUT RATHER THAN ADDING TWO ENTANGLED PHOTONS TO EXCITE A HIGHER-ENERGY LEVEL, IN QSRS THE EXCITATION PHOTONS MIX SUCH THAT THE DIFFERENCE IN THEIR ENERGIES IS MUCH SMALLER. THIS PROVIDES DIRECT ACCESS TO TERAHERTZ ENERGY RESONANCES. THZ SPECTROSCOPY WILL BE PERFORMED BY SWEEPING THE ENERGY DIFFERENCE BETWEEN THE EXCITATION PHOTONS BY SELECTING THE DESIRED ENERGIES OF THE TWO ENTANGLED PHOTONS GENERATED BY SPONTANEOUS PARAMETRIC DOWNCONVERSION. THZ SENSING AND HERALDED SINGLE THZ CARRIER GENERATION CAN BE PERFORMED BY SETTING THE ENERGY DIFFERENCE BETWEEN THE PHOTONS IN THE ENTANGLED PAIR TO A PARTICULAR RESONANCE AND LOOKING FOR THE UNIQUE PHOTON CORRELATION SIGNAL OF THE QSRS PROCESS. AFTER CHARACTERIZING THE SIGNAL ENHANCEMENT FROM ENTANGLEMENT AND OPTIMIZING THE QSRS MEASUREMENT TECHNIQUE, THE TEAM WILL IMPLEMENT PERTURBATIVE (FEW-PHOTON) THZ SPECTROSCOPY AND SENSING OF A VARIETY OF QUANTUM (SINGLE CARRIER) SYSTEMS TO ADDRESS CURRENT RESEARCH QUESTIONS, INCLUDING MEASUREMENTS OF THE FOLLOWING: PHONON DENSITY OF STATES IN QUANTUM MATERIALS, PHONON POPULATIONS DURING A METAL-INSULATOR TRANSITION, BAND SPLITTING IN HIGHLY CORRELATED ELECTRON STATES IN 2D MATERIAL HETEROSTRUCTURES, PLASMONIC ENHANCEMENT OF QSRS NEAR NANOSTRUCTURES, HERALDED SINGLE MAGNON GENERATION, AND LIPID SENSING IN TISSUE. THESE DIVERSE MEASUREMENTS WILL ESTABLISH QSRS AS A FLEXIBLE TOOL FOR SENSITIVE AND NON-DESTRUCTIVE SENSING THAT CAN BE USED FOR DIVERSE APPLICATIONS SUCH AS QUANTUM INFORMATION TECHNOLOGY, CANCER DIAGNOSTICS, NON-DESTRUCTIVE TESTING IN THE SEMICONDUCTOR INDUSTRY, AND CHEMICAL SENSING. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

MECHANISMS OF MEMBRANE RATCHETING DURING CELL INTERCALATION

THE BIOMECHANICS OF INTERCALATION IN GERM-BAND ELONGATION

MECHANISMS UNDERLYING READING AVOIDANCE IN CHILDREN WITH READING DIFFICULTIES. - PROJECT SUMMARY THIS AREA GRANT WILL EXPLORE INFORMATION PROCESSING (IP) MECHANISMS UNDERLYING READING AVOIDANCE IN YOUTH WITH A SPECIFIC LEARNING DISORDER IN READING (RD). FOR CHILDREN WITH RD, WEAKNESSES IN A SPECIFIC ACADEMIC SKILL (WORD DECODING) CAN IMPACT MANY DOMAINS OVER TIME, INCLUDING EDUCATIONAL AND OCCUPATIONAL ATTAINMENT AND MENTAL HEALTH. A MAJOR CONTRIBUTING FACTOR TO THESE IMPAIRMENTS IS REDUCED READING PRACTICE WHICH LIMITS EDUCATIONAL ACCESS CAUSING A CASCADE OF NEGATIVE OUTCOMES. INTERRUPTING THIS CASCADE REQUIRES INTERVENTIONS THAT ADDRESS THE FACT THAT MANY CHILDREN WITH RD AVOID READING EVEN AFTER THEY HAVE ACQUIRED THE NECESSARY DECODING SKILLS FROM EFFECTIVE READING INTERVENTIONS. THIS GRANT AIMS TO IDENTIFY MECHANISMS UNDERLYING READING AVOIDANCE IN CHILDREN WITH RD. AVOIDANCE AND ITS UNDERLYING MECHANISMS HAVE BEEN WELL-CHARACTERIZED IN MENTAL HEALTH, PARTICULARLY IN ANXIETY. IN THESE MODELS, THREE INFORMATION-PROCESSING (IP) BIASES TO THREAT DRIVE AVOIDANCE AND SUBSEQUENT ANXIETY: ATTENTION BIAS, ASSOCIATIVE LEARNING, AND AUTOMATIC ACTION TENDENCIES. THESE IP BIASES COULD BE RELATED TO READING AVOIDANCE AND SUBSEQUENT READING ANXIETY: READING-RELATED STIMULI MAY EVOKE INITIAL HYPERVIGILANCE FOLLOWED BY DISENGAGEMENT (ATTENTION BIAS, AIM 1A), LEARNED FEARFUL RESPONSES (ASSOCIATIVE LEARNING, AIM 1B), AND DISTANCING ACTIONS (AUTOMATIC ACTION TENDENCIES, AIM 1C) IN YOUTH WITH RD. WHILE THESE RELATIONSHIPS ARE CONFIRMED FOR ANXIETY, THEY HAVE YET TO BE TESTED IN RD (AIM 2). IN THIS PROPOSAL, WE AIM TO TEST WHETHER CHILDREN WITH RD EXHIBIT READING-RELATED IP BIASES THAT CONTRIBUTE TO READING AVOIDANCE AND READING ANXIETY. WE WILL RECRUIT CHILDREN AGES 10-12 WITH RD (N=60) AND WITHOUT RD (N=60). PARTICIPANTS WILL COMPLETE EXPERIMENTAL TASKS ASSESSING IP BIASES (ATTENTION BIAS, ASSOCIATIVE LEARNING, AUTOMATIC ACTION TENDENCIES), SELF- AND PARENT-REPORT MEASURES OF READING AVOIDANCE AND READING ANXIETY, AND STANDARDIZED READING ASSESSMENTS. IF SUCCESSFUL, THIS WORK COULD REPRESENT A SIGNIFICANT STEP FORWARD IN UNDERSTANDING MECHANISMS UNDERLYING READING AVOIDANCE, AND INFORM INTERVENTIONS TO TARGET IP BIASES THAT COULD AUGMENT AND IMPROVE LONG-TERM EFFECTS OF EXISTING READING INTERVENTIONS. THIS PROJECT HAS HIGH AND IMMEDIATE TRANSLATIONAL POTENTIAL, AND ALIGNS CLOSELY WITH NICHD’S CHILD DEVELOPMENT AND BEHAVIOR BRANCH’S RESEARCH PRIORITY: “USE OF NEUROCOGNITIVE RISK/PROTECTIVE FACTORS TO INFORM TARGETED TREATMENT STRATEGIES”. THE RESEARCH TEAM EXEMPLIFIES AN INTERDISCIPLINARY COLLABORATIVE APPROACH THAT BRIDGES ACROSS THE LEARNING DISABILITIES AND CHILD MENTAL HEALTH FIELDS WHICH HAVE TRADITIONALLY REMAINED QUITE SEPARATE. CENTRAL TO AREA GOALS, UNDERGRADUATE STUDENTS WILL BE INTEGRAL MEMBERS OF THE RESEARCH TEAM, RECEIVING INTENSIVE TRAINING IN CLINICAL RESEARCH AND COLLABORATIVE TEAM SCIENCE SKILLS.

EXTENDED AROMATIC POLYHETEROCYCLES VIA SCAFFOLD-GUIDED PHOTOINDUCED CASCADES

EXPLORING ROLES FOR FMR/P-BODIES IN PRESYNAPTIC DEVELOPMENT

LONG-DISTANCE SPIN TRANSPORT IN DISORDERED INSULATORS AND LOW-DAMPING METALS

INFLAMMATORY TRAJECTORIES ACROSS PREGNANCY: INVESTIGATING NOVEL MARKERS OF RISK FOR POSTPARTUM DEPRESSION - PROJECT SUMMARY POSTPARTUM DEPRESSION (PPD) IS THE MOST COMMON FORM OF PSYCHIATRIC ILLNESS OCCURRING AFTER CHILDBIRTH, AFFECTING NEARLY 18% OF WOMEN GLOBALLY AND CONTRIBUTING TO SUFFERING AND IMPAIRED FUNCTIONING IN BOTH MOTHERS AND THEIR CHILDREN. TO ELUCIDATE FACTORS THAT CONTRIBUTE TO PPD RISK, THE CURRENT PROJECT SEEKS TO TEST THE ROLE OF INFLAMMATORY MARKERS ACROSS PREGNANCY IN THE PREDICTION OF POSTPARTUM DEPRESSIVE SYMPTOMS. SPECIFICALLY, REFLECTING RECENT THEORETICAL WORK ON THE COMPLEX AND SHIFTING ROLE OF THE IMMUNE SYSTEM DURING PREGNANCY, THE CURRENT PROJECT WILL UTILIZE A PROSPECTIVE LONGITUDINAL DESIGN OF 165 PREGNANT WOMEN TO EXAMINE DYNAMIC TRAJECTORIES OF INFLAMMATORY MARKERS ACROSS PREGNANCY IN THE PREDICTION OF PPD SYMPTOMS AND DIAGNOSIS AT ONE- AND TWO- MONTHS POSTPARTUM. THROUGH REPEATED ASSESSMENTS ACROSS THE PRENATAL AND POSTPARTUM PERIODS, BY CONSIDERING POTENTIALLY CURVILINEAR TRAJECTORIES OF INFLAMMATORY MARKERS INSTEAD OF SINGLE ASSESSMENTS, AND BY EXAMINING A RANGE OF IMMUNOLOGICAL MARKERS SIMULTANEOUSLY, WE WILL OVERCOME PAST ROADBLOCKS TO PROGRESS AND MORE CLOSELY MIRROR THE ALTERNATING IMMUNOLOGICAL PRIORITIES OF PREGNANCY. LEVERAGING STORED PLASMA SAMPLES COLLECTED PRIOR TO THE COVID-19 PANDEMIC AS PART OF A PARENT R01 STUDY OF DEPRESSIVE SYMPTOMS DURING PREGNANCY (MH109662), THIS WORK WILL CHARACTERIZE TRAJECTORIES OF KEY DEPRESSION-RELEVANT INFLAMMATORY MARKERS ACROSS EACH TRIMESTER OF PREGNANCY IN WOMEN WITH AND WITHOUT ELEVATED PRENATAL DEPRESSIVE SYMPTOMS (AIM 1) AND EXAMINE WHETHER INFLAMMATORY TRAJECTORIES PROSPECTIVELY PREDICT DEPRESSIVE SYMPTOMS AND PPD DIAGNOSIS AT ONE- AND TWO-MONTHS POSTPARTUM (AIM 2). AS WELL, IT WILL PROBE THE PREDICTIVE SPECIFICITY OF DEPRESSION-RELEVANT INFLAMMATORY MARKERS (VERSUS SHIFTS IN TH1 AND TH2 CYTOKINES OR INFLAMMATORY MARKERS IMPLICATED IN OTHER PSYCHIATRIC DISORDERS) AND WILL EXPLORE WHETHER INFLAMMATORY PROFILES IN PREGNANCY DIFFERENTIALLY RELATE TO CERTAIN PPD SYMPTOMS (AIM 3). THROUGH THIS METHODOLOGICALLY RIGOROUS APPROACH, WE WILL BE POISED TO CONDUCT STRONG TESTS OF DIRECTIONAL ASSOCIATIONS BETWEEN PRENATAL INFLAMMATION AND POSTPARTUM DEPRESSIVE SYMPTOMS AND TO IDENTIFY INFLAMMATORY PARAMETERS THAT MAY SERVE AS RISK BIOMARKERS. IN DOING SO, INSIGHTS FROM THIS PROJECT WILL BE CRITICAL FOR ADVANCING FUTURE HYPOTHESES TO ELUCIDATE THE PRECISE NEUROBIOLOGICAL CASCADES THAT ACCOUNT FOR LINKS BETWEEN INFLAMMATION AND POSTPARTUM DEPRESSIVE SYMPTOMS, WITH THE ULTIMATE GOAL TO IDENTIFY NOVEL FACTORS TO TARGET IN THE PREVENTION OR TREATMENT OF POSTPARTUM DEPRESSION.

GOALS, OBJECTIVES, RESEARCH QUESTIONS: YOUTH GUN VIOLENCE IS A PRESSING CRIMINAL JUSTICE PROBLEM IN THE UNITED STATES. ALTHOUGH YOUTH DIVERSION PROGRAMS SHOW PROMISE IN REDUCING YOUTH FIREARM RECIDIVISM, GUN-RELATED OFFENSES ARE OFTEN NOT ELIGIBLE FOR PARTICIPATION IN YOUTH DIVERSION PROGRAMS. TO ADDRESS THIS GAP, THIS PROJECT RESPONDS TO PRIORITY 1A OF THE NIJ FY24 FIELD-INITIATED ACTION RESEARCH PARTNERSHIPS TO IDENTIFY ACTIONABLE, DATA-DRIVEN, AND EVIDENCE-BASED DECISION-MAKING TO GUIDE THE ONGOING DEVELOPMENT OF THE DENVER HANDGUN INTERVENTION PROGRAM (HIP). HIP IS A SPECIALIZED COURT FOR YOUTH CHARGED WITH GUN-RELATED OFFENSES AND THEIR FAMILIES, DEVELOPED AND LAUNCHED IN 2021 IN DENVER (COLORADO). THE PROJECT HAS TWO GOALS. GOAL 1: ADVANCE EQUITY AND REMOVE BARRIERS TO ACCESSING SERVICES AND OPPORTUNITIES THROUGH DENVERS HIP. THEREFORE, WE WILL: OBJECTIVE 1.1: EMPLOY AN ACTION RESEARCH EVALUATION APPROACH TO ASSESS RESPONSE TO CHANGES AND PROGRAM IMPACT; OBJECTIVE 1.2: APPLY A DATA-DRIVEN, PROBLEM-SOLVING APPROACH TO CHALLENGES PRIORITIZED BY THE HIP MULTIDISCIPLINARY TEAM (MDT)OBJECTIVE 1.3: IMPLEMENT PROGRAM CHANGES; OBJECTIVE 1.4: IDENTIFY ACTIONABLE AND MEASURABLE RESPONSES TO PROGRAM CHANGES. GOAL 2: PROVIDE A NATIONAL MODEL FOR IMPROVING JUVENILE JUSTICE OUTCOMES THROUGH COLLABORATION AND ONGOING EVALUATION. THEREFORE, WE WILL: OBJECTIVE 2.1: DEVELOP A SUSTAINABLE APPROACH TO ONGOING DATA COLLECTION AND USE AS WELL AS PRACTITIONER-RESEARCHER PARTNERSHIP; OBJECTIVE 2.2: DISSEMINATE ACTIONABLE, DATA-DRIVEN RECOMMENDATIONS FOR PRACTITIONER-RESEARCH PARTNERSHIPS AND JUVENILE JUSTICE COLLABORATIONS. THE PROJECT ADDRESSES THREE RESEARCH QUESTIONS: 1) IS A SPECIALIZED COURT FOR YOUTH CHARGED WITH GUN-RELATED OFFENSES LINKED WITH POSITIVE JUVENILE JUSTICE AND RELATED OUTCOMES? 2) WHAT PROGRAM COMPONENTS ARE LINKED WITH ACHIEVING PROGRAM GOALS? 3) HOW CAN AN MDT ADOPT DATA-DRIVEN, PROBLEM-SOLVING APPROACHES TO SUSTAIN EFFECTIVE PRACTICES AND ONGOING IMPROVEMENT IN SAFETY AND JUSTICE OUTCOMES FOR YOUTH AND THEIR FAMILIES FOLLOWING HANDGUN OFFENSES? RESEARCH DESIGN AND METHODS: PROJECT ACTIVITIES WILL BE CARRIED OUT THROUGH A RESEARCHER-PRACTITIONER COLLABORATION. DRAWING ON A PROGRAM LOGIC MODEL AS WELL AS PROJECT GOALS, OBJECTIVES, AND RESEARCH QUESTIONS, THE OVERALL APPROACH EMPHASIZES THREE KEY DESIGN ELEMENTS: 1) USE OF MULTIPLE DATA SOURCES OVER TIME; 2) ACTION RESEARCH; 3) MEANINGFUL ENGAGEMENT OF YOUTH AND PARENTS/GUARDIANS FROM HISTORICALLY UNDERSERVED AND MARGINALIZED COMMUNITIES. WORK PRODUCTS AND DISSEMINATION PLAN: THIS PROJECT IS DESIGNED TO INFORM NATIONAL POLICY AND PRACTICE, AND WILL RESULT IN MULTIPLE PRODUCTS FOR PRACTITIONERS, POLICYMAKERS, AND PUBLIC AUDIENCES AND RESEARCHERS. PRODUCTS DESCRIBING STUDY FINDINGS AND ACTIONABLE RECOMMENDATIONS WILL BE DISSEMINATED USING STRATEGIES THAT BUILD ON OUR TEAMS SUCCESS SHARING RESEARCH WITH POLICY AND PRACTICE GROUPS.CA/NCF

MODELING AND CONTROL OF A NEXTGEN CIRCULATION CONTROL BASED UNMANNED AERIAL VEHICLES

MECHANISMS OF DELTA-LIKE 4 ENDOCYTOSIS AND NOTCH ACTIVATION DURING BLOOD VESSEL DEVELOPMENT - SUMMARY ENDOTHELIAL CELLS (ECS) ARE THE CELL TYPE RESPONSIBLE FOR THE BULK OF EMBRYONIC BLOOD VESSEL FORMATION, EVENTUALLY LEADING TO AN ESTIMATED 100,000 MILES OF VASCULATURE BY ADULTHOOD. DURING DEVELOPMENT, NEW BLOOD VESSELS EMERGE FROM PRE-EXISTING VASCULATURE, A PROCESS TERMED ANGIOGENESIS. NOTCH SIGNALING IS FUNDAMENTAL TO ANGIOGENESIS AND ADULT BLOOD VESSEL HOMEOSTASIS. IN THE ABSENCE OF NOTCH, BLOOD VESSELS DEMONSTRATE A CHRONIC SPROUTING PHENOTYPE MARKED BY UNCHECKED PROLIFERATION AND OVERGROWTH; THIS EVIDENCE AND OTHERS OVERWHELMINGLY SHOW NOTCH IS REQUIRED FOR BLOOD VESSEL MATURATION AND STABILITY. WHEN LIGAND-BOUND, THE NOTCH INTRACELLULAR DOMAIN IS CLEAVED AND TRANSLOCATES TO THE NUCLEUS, ACTING AS A TRANSCRIPTION FACTOR. DELTA-LIKE LIGAND 4 (DLL4) IS A POTENT NOTCH LIGAND THAT BINDS TO THE EXTRACELLULAR DOMAIN OF NOTCH. TO ELICIT NOTCH ACTIVATION THE ECTODOMAIN OF NOTCH REQUIRES A PULLING FORCE BY DLL4 TO EXPOSE A S2 CLEAVAGE SITE. ONCE EXPOSED, THE NOTCH EXTRACELLULAR DOMAIN IS CLEAVED, ALLOWING FOR RELEASE OF THE NOTCH INTRACELLULAR DOMAIN (NICD) STIMULATING SIGNALING ACTIVATION. VERY LITTLE IS KNOWN ABOUT THE POST-TRANSCRIPTIONAL REGULATION OF DLL4, AND EVEN LESS IS UNDERSTOOD ABOUT THE MECHANISMS BY WHICH DLL4 EXERTS A SUSTAINED PULLING FORCE TO ACTIVATE NOTCH-MEDIATED LATERAL INHIBITION. OUR PRELIMINARY DATA DESCRIBES, FOR THE FIRST TIME, HOW DLL4 ENDOCYTOSIS AND ANCHORING TO THE ACTIN CYTOSKELETON GENERATES THE MECHANICAL FORCE REQUIRED TO EXPOSE THE S2 SITE OF NOTCH. SPECIFICALLY, THIS PROPOSAL WILL FOCUS ON TWO LARGELY UNCHARACTERIZED PROTEINS WE BELIEVE ARE CENTRAL TO FORCE- GENERATING DLL4 ENDOCYTOSIS, EPS15 HOMOLOGY DOMAIN BINDING PROTEIN 1 (EHBP1) AND EH DOMAIN CONTAINING PROTEIN 2 (EHD2). OUR BROAD HYPOTHESIS IS THAT EHBP1 ANCHORS EHD2 TO F-ACTIN FILAMENTS, AIDING IN THE TRANSENDOCYTOSIS OF DLL4 BOUND TO NOTCH. IN AIM1 WE WILL DETAIL HOW BOTH EHBP1 AND EHD2 WORK IN COMBINATION TO FACILITATE DLL4 ENDOCYTOSIS, AND IN DOING SO, MEDIATE NOTCH SIGNALING. IN AIM2, WE WILL COMPREHENSIVELY DEMONSTRATE THAT EHBP1 AND EDH2 WORKS IN COMBINATION TO REGULATE DLL4 ENDOCYTOSIS AND DOWNSTREAM NOTCH ACTIVITY DURING ZEBRAFISH BLOOD VESSEL MORPHOGENESIS USING LIVE-IMAGING AND CRISPR- BASED MUTANT GENERATION. OVERALL, THIS PROPOSAL WILL ANSWER SEVERAL CRITICALLY IMPORTANT QUESTIONS PERTAINING TO BLOOD VESSEL DEVELOPMENT AS WELL AS PROVIDE A POWERFUL TRAINING OPPORTUNITY FOR UNDERGRADUATE SCHOLARS.

COLLABORATIVE RESEARCH: THE STRUCTURE OF ARTHROPOD FOOD WEBS: CONSEQUENCES OF NUTRIENT-LOADING SCENARIOS FOR PRODUCTIVITY TROPHIC COMPOSITION AND FO

CANNABIS USE DURING PREGNANCY, MATERNAL BRAIN, AND MOTHER-INFANT RELATIONSHIPS

OUR STORIES, OUR MEDICINE ARCHIVES: A CULTURE CENTERED DIABETES AND CARDIOVASCULAR DISEASE HEALTH INFORMATION INTERFACE FOR URBAN AMERICAN INDIAN AND ALASKA NATIVE AND INDIGENOUS COMMUNITIES - PROJECT SUMMARY/ABSTRACT AMERICAN INDIANS AND ALASKA NATIVES (AIAN) AND INDIGENOUS POPULATIONS EXPERIENCE DISPROPORTIONATELY HIGH RATES OF DIABETES AND CARDIOVASCULAR DISEASE (CVD) AND LACK ACCESS TO RELIABLE HEALTH CARE AND HEALTH INFORMATION. TRAUMATIC STRESSORS SUCH AS RACIAL DISCRIMINATION AND DISRUPTIONS TO SOCIAL AND CULTURAL HEALTH TRADITIONS ARE LIKELY TO BE CONNECTED TO POOR HEALTH OUTCOMES INCLUDING CHRONIC PREVENTABLE HEALTH ISSUES SUCH AS DIABETES AND CVD. FOR AIAN POPULATIONS, THIS LINK IS ESPECIALLY RELEVANT. CENTURIES OF TRAUMATIC EVENTS HAVE CONTRIBUTED TO DEVASTATING HEALTH OUTCOMES IN AIAN COMMUNITIES. OVER THE LAST SEVERAL DECADES, THE ROLE OF CULTURAL HEALING PRACTICES HAS BEEN RECOGNIZED AS AN IMPORTANT APPROACH TO TREATING ACUTE AS WELL AS CHRONIC HEALTH CONDITIONS. HOWEVER, URBAN AIANS, APPROXIMATELY 70% OF THE NATIONAL AIAN POPULATION, OFTEN LACK EITHER CULTURAL OR MEDICAL RESOURCES. ACCESS TO ONLINE HEALTH INFORMATION, HOWEVER, CAN POSITIVELY IMPACT CONSUMER HEALTHCARE BOTH DIRECTLY AND INDIRECTLY AND OFFERS AN OPPORTUNITY FOR URBAN AIANS. THE OUR STORIES, OUR MEDICINE ARCHIVE (OSOMA) SEEKS TO LEVERAGE WEB-BASED ACCESS TO HEALTH INFORMATION BY PROVIDING TRADITIONAL INDIGENOUS HEALTH KNOWLEDGE INFORMATION ALONG WITH WIDELY AVAILABLE EVIDENCE-BASED AND EMERGENT PRACTICES FOR DIABETES AND CVD SPECIFIC TO AIAN COMMUNITIES. THE OSOMA PROJECT PRESENTS A NOVEL APPROACH TO ADDRESSING HEALTH DISPARITIES IN URBAN AIAN COMMUNITIES THROUGH LOCATING DIABETES AND CARDIOVASCULAR DISEASE INFORMATION WITHIN AN INTERACTIVE COMMUNITY-BASED PARTICIPATORY DIGITAL ARCHIVE THAT IS CREATED BY AND FOR URBAN AIANS. WE PROPOSE 4 SPECIFIC AIMS: AIM 1: FORM AND CONVENE A CAB OF HEALTH SCIENCES LIBRARIANS, PHYSICIANS, AIAN HEALTH EXPERTS, AND COMMUNITY MEMBERS TO ENSURE A CULTURALLY RESPONSIVE APPROACH TO THE ARCHIVE AND INTERFACE DESIGN AND RESEARCH PROCESS. AIM 2: CONDUCT CONTENT ANALYSES ACROSS AND WITHIN 50 ORAL HISTORY INTERVIEWS AND CORRESPONDING ARCHIVAL MATERIALS TO CREATE CULTURALLY RELEVANT HEALTH INFORMATION MODULES RELATED TO DIABETES AND CVD PREVENTION. AIM 3: DESIGN, DEVELOP AND LAUNCH A COMMUNITY-BASED PARTICIPATORY DIGITAL ARCHIVE AND HEALTH INFORMATION INTERFACE CENTERING ON TRADITIONAL INDIGENOUS HEALTH KNOWLEDGE ABOUT DIABETES AND CVD WITH AND FOR URBAN AIAN INDIVIDUALS. AIM 4: EVALUATE THE ACCESSIBILITY OF HEALTH INFORMATION CONTENT, USABILITY OF THE HEALTH INFORMATION MODULES AND INTERFACE, AND NARRATIVE ENGAGEMENT WITH THE ARCHIVAL AND HEALTH INFORMATION MATERIALS. ONCE THE INTERFACE IS LAUNCHED WE WILL ASSESS THE ACCESSIBILITY OF CONTENT, INTERFACE USABILITY, AND THE EXTENT TO WHICH 100 URBAN AIAN PARTICIPANTS ENGAGE WITH NARRATIVE CONTENT (E.G. STORIES EXCERPTED FROM ORAL HISTORIES).

LINKS AMONG ADOLESCENT EXECUTIVE FUNCTION, EFFORTFUL CONTROL AND PSYCHOPATHOLOGY

BIOLOGICAL CORRELATES OF ALZHEIMER IN DOWN SYNDROME.

POLYAMINES IN DOWN SYNDROME-ALZHEIMER'S DISEASE

UNDERSTANDING THE MECHANOBIOLOGICAL MECHANISMS OF SOFT TISSUE DEFECTS AND RUPTURE - PROJECT SUMMARY SOFT TISSUE DEFECTS ARE A PREVALENT CLINICAL CHALLENGE IN HUMAN HEALTH. THEY MAY ARISE FROM GENETIC PREDISPOSITIONS, TRAUMA, OR ROUTINE SURGICAL PROCEDURES. WHEN THESE DEFECTS FAIL TO HEAL, THEY COMPROMISE TISSUE INTEGRITY, IMPAIR ORGAN FUNCTION AND CAN PROGRESS TO CHRONIC ILLNESS OR RUPTURE. SUCH RUPTURE EVENTS ARE OFTEN CATASTROPHIC AND REMAIN A MAJOR SOURCE OF MORBIDITY AND MORTALITY WORLDWIDE. WHILE MANY GENETIC, MOLECULAR, AND CELLULAR FACTORS RENDER THE TISSUE SUSCEPTIBLE TO DAMAGE, IT IS THE SUBSEQUENT CHANGES IN THE MACROSCOPIC MECHANICS AND THE INTERPLAY BETWEEN STRESS AND STRENGTH THAT ULTIMATELY DICTATE WHETHER THE DEFECT HEALS OR RUPTURES. YET, THE MECHANOBIOLOGICAL MECHANISMS DRIVING RUPTURE ARE NOT FULLY UNDERSTOOD, IN PART BECAUSE CURRENT METHODS FOR STUDYING RUPTURE AVERAGE PROPERTIES OVER THE ENTIRE SPECIMEN AND FAIL TO CAPTURE THE INHERENTLY LOCAL NATURE OF TISSUE DEGENERATION, FAILURE, AND RUPTURE. THIS PROGRAM ADDRESSES THIS GAP BY ADVANCING AN INNOVATIVE MULTIMODAL FRAMEWORK FOR LOCAL MECHANOBIOLOGICAL ASSESSMENT OF SOFT TISSUE DEFECTS. USING PANORAMIC DIGITAL IMAGE CORRELATION, OPTICAL COHERENCE TOMOGRAPHY, HISTOLOGY, MULTIPHOTON IMAGING, AND TRANSCRIPTOMICS, WE WILL GENERATE HIGH-RESOLUTION, SPATIALLY ALIGNED DATASETS TO UNCOVER LOCAL STRUCTURE–FUNCTION RELATIONSHIPS AT AND AROUND DEFECTS. UTILIZING THE MOUSE CAROTID ARTERY, TRACHEA, AND STOMACH AS REPRESENTATIVE SOFT TISSUE SYSTEMS, WE WILL INVESTIGATE HOW DEFECT LOCATION, GEOMETRY, AND COMPOSITION INFLUENCE RUPTURE THRESHOLDS AND HEALING DYNAMICS. IN THE FIRST EXPERIMENTAL PROJECT WE WILL STUDY EX VIVO-GENERATED DEFECTS TO TEST HOW DEFECT SIZE, LOCATION, AND COMPOSITION ALTER LOCAL MECHANICAL PROPERTIES AND RUPTURE POTENTIAL. IN THE SECOND EXPERIMENTAL PROJECT, WE WILL USE IN VIVO MODELS TO EXAMINE HOW BIOLOGICALLY GENERATED DEFECTS REMODEL UNDER PHYSIOLOGICAL CONDITIONS, INCORPORATING ANALYSES OF EXTRACELLULAR MATRIX REORGANIZATION, INFLAMMATION, AND TRANSCRIPTIONAL SIGNATURES. FINALLY, THE RESULTING DATA WILL INFORM A COMPUTATIONAL PROGRAM TO MODEL DEFECT INITIATION, REMODELING, AND FAILURE. BY INTEGRATING GRADUAL DEFECT GROWTH THROUGH PHASE-FIELD FINITE ELEMENT ANALYSIS WITH RUPTURE EVENTS CAPTURED BY SMOOTHED PARTICLE HYDRODYNAMICS, THESE MODELS WILL ALLOW DIRECT PREDICTION OF RUPTURE BEHAVIOR FROM EXPERIMENTAL DATA. TOGETHER, THIS INTEGRATED APPROACH WILL PROVIDE THE FIRST FRAMEWORK TO IDENTIFY KEY MECHANOBIOLOGICAL FACTORS THAT COMPROMISE STRENGTH AND EXPLAIN WHY SOME DEFECTS RUPTURE WHILE OTHERS HEAL. ALTOGETHER, BY APPLYING A FRAMEWORK FOR LOCAL MECHANOBIOLOGICAL ASSESSMENT TO THE COMPLEX PROBLEM OF SOFT TISSUE DEFECTS, OUR WORK WILL YIELD CRITICAL INSIGHTS INTO SPATIOTEMPORAL RUPTURE PREDICTION AND MANAGEMENT OF DEFECTS, ULTIMATELY GUIDING STRATEGIES FOR SURGICAL DECISION-MAKING, DEVICE DESIGN, AND REGENERATIVE THERAPIES.

DEFINING THE BUILDING BLOCKS OF MULTICELLULARITY: ADHESION, RECOGNITION, AND IMMUNITY - THE EVOLUTION OF MULTICELLULARITY WAS A PIVOTAL TRANSITION THAT LAID THE FOUNDATION FOR CELL BIOLOGY, DEVELOPMENT, PHYSIOLOGY, AND IMMUNITY IN ANIMALS. BUILDING ON OUR PREVIOUS WORK IN CELL-CELL ADHESION AND SELF/NONSELF RECOGNITION AS UNIFYING ELEMENTS OF MULTICELLULAR DEVELOPMENT, IN THE NEXT FIVE YEARS WE WILL EXAMINE THE EVOLUTIONARY FOUNDATIONS OF ANTIBACTERIAL IMMUNITY. OUR WORK CENTERS ON SPONGES, INVERTEBRATE ANIMALS WITH UNIQUE RELEVANCE FOR IDENTIFYING BOTH ANCIENTLY CONSERVED AND NOVEL IMMUNE PARADIGMS FOR REGULATING INTERACTIONS WITH BACTERIA. LIKE ALL ANIMALS, SPONGES MUST DEFEND AGAINST OPPORTUNISTIC PATHOGENS, BUT LIKE PROTISTS THEY FEED BY DIRECT PHAGOCYTOSIS OF BACTERIA. ALSO, LIVING IN AQUATIC HABITATS THEY ARE CONSTANTLY BATHED IN ENVIRONMENTAL BACTERIA FROM WHICH THEY CULTIVATE COMPLEX COMMUNITIES OF BENEFICIAL SYMBIONTS WITHIN THEIR TISSUES. WITH GENOMIC RESOURCES, A CELL ATLAS, AND TRANSGENIC TOOLS IN-HAND, WE ARE UNIQUELY POSITIONED TO PROBE SPONGE IMMUNE PATHWAYS IN UNPRECEDENTED DEPTH. OUR PRELIMINARY FINDINGS HAVE ALREADY REVEALED A NOVEL FAMILY OF GLYCAN-BINDING PATTERN RECOGNITION RECEPTORS (PRRS) THAT HAVE NEVER BEFORE BEEN STUDIED. CHARACTERIZING THEIR BIOCHEMICAL AND FUNCTIONAL PROPERTIES WILL PROVIDE CRITICAL NEW INSIGHTS INTO BACTERIAL RECOGNITION AND RESPONSE. FURTHERMORE, THE GLYCAN-BINDING REGION OF THESE PRRS IS COMPOSED OF THREE-SIDED BETA-HELICES THAT HOLD TREMENDOUS PROMISE AS NOVEL DIAGNOSTIC AND THERAPEUTIC TOOLS. WE HAVE ALSO ESTABLISHED THAT THE VERSATILE INTRACELLULAR PATHOGEN LEGIONELLA PNEUMOPHILA CAN BE USED TO INFECT SPONGES AND THEREBY MODEL AN AUTHENTIC IMMUNE RESPONSE. AS L. PNEUMOPHILA INFECTION HAS BEEN EXTENSIVELY STUDIED IN HUMAN MACROPHAGES AND AMOEBAE, THERE EXISTS A RICH FRAMEWORK FOR COMPARING INFECTION DYNAMICS ACROSS NEARLY 1.8 BILLION YEARS OF EVOLUTIONARY HISTORY, SPANNING THE DIVIDE BETWEEN UNICELLULARITY AND MULTICELLULARITY. OUR RESEARCH SEEKS TO DEFINE FOUNDATIONAL PRINCIPLES OF IMMUNITY, BRIDGING EVOLUTIONARY BIOLOGY AND BIOMEDICAL SCIENCE TO ADDRESS CRITICAL CHALLENGES IN HEALTH AND DISEASE.

ULTRASENSITIVE PHOTOAMPLIFED FLUORESCENCE DETECTION OF LIGAND BINDING ON A CHIP

MOLECULAR MECHANISMS OF LYSOSOME REMODELING IN RESPONSE TO CELLULAR STRESS - PROJECT SUMMARY THE LYSOSOME IS A CENTRAL CATABOLIC STATION THAT BREAKS DOWN AND RECYCLES MATERIALS FROM MULTIPLE PATHWAYS. LYSOSOME DYSFUNCTION WILL CAUSE LYSOSOMAL STORAGE DISEASES. IN ADDITION, LYSOSOME DYSREGULATION IS ALSO WIDELY RELATED TO MANY OTHER HUMAN DISEASES, SUCH AS NEURODEGENERATIVE DISORDERS, CARDIOVASCULAR DISEASES, OSTEOPOROSIS, AND CANCERS. TO FUNCTION PROPERLY, THE COMPOSITION OF LYSOSOME MEMBRANE MUST BE PRECISELY REGULATED IN RESPONSE TO ENVIRONMENTAL CUES. DYSREGULATION IN LYSOSOME MEMBRANE COMPOSITION LEADS TO LYSOSOME DYSFUNCTION AND THE DEVELOPMENT OF LYSOSOME-RELATED DISEASES. DESPITE EXTENSIVE RESEARCH INTO MANY OTHER ASPECTS OF LYSOSOME BIOLOGY, HOW LYSOSOME ADJUSTS ITS OWN COMPOSITION IN RESPONSE TO ENVIRONMENTAL CUES REMAINS POORLY UNDERSTOOD. SURPRISINGLY, WE FOUND THAT MANY LYSOSOME MEMBRANE PROTEINS ARE DEGRADED UNDER STARVATION. THIS SUGGESTS THAT, RATHER THAN SIMPLY GLOBAL BIOGENESIS, THE LYSOSOME MEMBRANE UNDERGOES DRAMATIC REMODELING, CHALLENGING THE LONG-HELD VIEW OF HOW LYSOSOMAL COMPOSITION IS REGULATED. HOWEVER, THE CELLULAR MACHINERY AND MOLECULAR MECHANISMS GOVERNING THESE PROCESSES ARE STILL LARGELY UNKNOWN, POSITIONING THIS PROPOSED RESEARCH AT THE FOREFRONT OF THE FIELD. IN THIS PROPOSAL, WE WILL USE BUDDING YEAST AS A MODEL SYSTEM TO ADDRESS THIS EMERGING QUESTION THROUGH TWO MAJOR DIRECTIONS:1. CHARACTERIZATION OF VACUOLE MEMBRANE PROTEIN (VMP) DEGRADATION PATHWAYS. 2. VACUOLE REMODELING THROUGH TRANSCRIPTIONAL REGULATION. COLLECTIVELY, THE RESULTS OF OUR STUDIES WILL ADVANCE THE FIELD BY UNCOVERING THE NEW MACHINERY AND MECHANISMS INVOLVED IN BOTH THE DEGRADATION AND PRODUCTION ASPECTS OF LYSOSOMAL REMODELING. FURTHERMORE, THIS PROPOSED RESEARCH WILL BE A CRITICAL FIRST STEP IN UNDERSTANDING THE ROLE OF LYSOSOMAL REMODELING IN LYSOSOMAL FUNCTION AND LYSOSOME-RELATED DISEASES. IT WILL ALSO LAY THE FOUNDATION FOR DEVELOPING NEW THERAPEUTIC TREATMENTS THAT TARGET LYSOSOMAL FUNCTION BY CONTROLLING ITS COMPOSITION.

POST-TRANSCRIPTIONAL REGULATION OF TISSUE REGENERATION BY RNP-GRANULES - PROJECT SUMMARY P-BODIES ARE RIBONUCLEOPROTEIN GRANULES THAT FORM MEMBRANELESS COMPARTMENTS THROUGH LIQUID-LIQUID PHASE SEPARATION AND REGULATE GENE EXPRESSION BY DIRECTING MRNAS FOR DEGRADATION, TRANSLATION, OR STORAGE. IN HUMANS, P-BODIES ARE ESTIMATED TO INFLUENCE ONE-THIRD OF GENES IN THE GENOME. RECENT RESEARCH HIGHLIGHTS THEIR INVOLVEMENT IN STEM CELLS, WHERE THEY REGULATE CELL CYCLING AND CELL FATE DECISIONS. DESPITE THESE ADVANCES, LITTLE IS KNOWN ABOUT HOW P-BODIES FUNCTION IN CONNECTIVE TISSUE OR DURING TISSUE REGENERATION. OUR RECENT WORK USING IN VIVO PROXIMITY LABELING IN ZEBRAFISH IDENTIFIED DDX61, A PROTEIN CENTRAL TO P-BODY FORMATION, AS CRITICAL DURING REGENERATION. DDX61 FORMS CONDENSATES REMINISCENT OF P-BODIES, AND ITS LOSS IS ASSOCIATED WITH REDUCED CELL PROLIFERATION AND IMPAIRED TISSUE REGENERATION. INTERESTINGLY, THESE REGENERATIVE P-BODIES FORM IN RESPONSE TO INJURY AND DISSIPATE ONCE REGENERATION IS COMPLETE, SUGGESTING THEY ARE DYNAMICALLY REGULATED. THESE FINDINGS PROVIDE A STRONG FOUNDATION TO EXPLORE THE MECHANISMS OF P-BODY FORMATION AND THEIR FUNCTIONAL SIGNIFICANCE IN REGENERATION. IN MY NEWLY ESTABLISHED LABORATORY, WE AIM TO ADDRESS THE MECHANISMS UNDERLYING P-BODY FORMATION AND FUNCTION IN THE CONTEXT OF TISSUE REGENERATION. SPECIFICALLY, WE WILL DETERMINE THE COMPOSITION OF REGENERATIVE P-BODIES USING INNOVATIVE TOOLS, INCLUDING IN VIVO PROXIMITY LABELING AND SUPER-RESOLUTION MICROSCOPY. TO ESTABLISH CAUSALITY, WE WILL BIOENGINEER ARTIFICIAL P-BODIES AND TEST THEIR ABILITY TO REGULATE MRNA FATE IN ZEBRAFISH. THIS WILL BE ONE OF THE FIRST COMPREHENSIVE STUDIES ON THE POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION BY P-BODIES IN CONNECTIVE TISSUE AND DURING TISSUE REGENERATION. BY UNCOVERING HOW REGENERATIVE P-BODIES REGULATE CELL DIVISION AND DIFFERENTIATION, THIS RESEARCH WILL ADVANCE OUR UNDERSTANDING OF POST-TRANSCRIPTIONAL REGULATION AND PROVIDE A FOUNDATION FOR DEVELOPING NOVEL THERAPEUTIC STRATEGIES FOR TISSUE REGENERATION, AGING, AND CANCER.

POVERTY, CHRONIC STRESS AND NEURAL REGULATION OF MATERNAL MOOD AND PARENTING

THREAT INTERPRETATION BIAS AS COGNITIVE MARKER AND TREATMENT TARGET IN PEDIATRIC ANXIETY

ELUCIDATING AN INHIBITORY ROLE OF MAP2 IN TAU FIBRILLIZATION

THE CALORIMETRIC ELECTRON TELESCOPE (CALET) IS A AN EXPERIMENT TO STUDY COSMIC RAY ELECTRONS, GAMMA-RAYS AND NUCLEONS IN THE ENERGY RANGE UP TO 10 TE

ESTABLISHING AN ASSAY FOR DETECTING SINGLE TAU FIBRILS

RANDOMIZED CLINICAL TRIAL_ REDUCE SUBSTANCE USE_VICTIMIZATION IN HOMELESS YOUTH

REU SITE: SUMMER ENGINEERING RESEARCH EXPERIENCES IN POWER AND ENERGY SYSTEMS FOR SMART CITIES -THIS NSF PROJECT AIMS TO ENGAGE UNDERGRADUATE STUDENTS IN TRANSFORMATIVE RESEARCH EXPERIENCES FOCUSED ON SMART CITIES, WITH AN EMPHASIS ON SMART POWER AND ENERGY SYSTEMS. THE PROGRAM ADDRESSES NATIONAL PRIORITIES IN ENERGY SECURITY, INFRASTRUCTURE RESILIENCE, AND WORKFORCE DEVELOPMENT BY PREPARING STUDENTS TO TACKLE THE COMPLEX CHALLENGES THAT ARISE AT THE INTERSECTION OF ENERGY, ECONOMY, AND TECHNOLOGY IN URBAN SETTINGS. THIS WILL BE ACHIEVED THROUGH HANDS-ON RESEARCH, INTERDISCIPLINARY MENTORSHIP, AND EXPOSURE TO REAL-WORLD APPLICATIONS VIA SITE VISITS TO UTILITIES, INDUSTRIES, AND NATIONAL LABORATORIES. THE INTELLECTUAL MERITS OF THE PROJECT INCLUDE ADVANCING STUDENT RESEARCH IN ARTIFICIAL INTELLIGENCE FOR ENERGY SYSTEMS, DATA ANALYTICS AND QUANTUM COMPUTING, ENERGY STORAGE, AND ELECTRIC GRID RESILIENCY, WHILE FOSTERING CROSS-DISCIPLINARY THINKING IN URBAN INFRASTRUCTURE. THE BROADER IMPACTS OF THE PROJECT INCLUDE CONTRIBUTING TO THE PROGRESS OF SCIENCE AND THE NATIONAL WELFARE BY DEVELOPING A NEW GENERATION OF RESEARCHERS TRAINED IN AREAS ESSENTIAL TO FUTURE ENERGY SYSTEMS. IT EXPANDS ACCESS TO HIGH-QUALITY STEM RESEARCH EXPERIENCES FOR UNDERGRADUATE STUDENTS ACROSS THE UNITED STATES. BY FOSTERING BROAD PARTICIPATION, THE PROGRAM CONTRIBUTES TO BUILDING A SKILLED AND URGENTLY NEEDED ENERGY WORKFORCE THAT REFLECTS THE FULL TALENT OF THE AMERICAN POPULATION. THE TECHNICAL GOALS OF THE PROJECT FOCUS ON EQUIPPING STUDENTS TO ADDRESS CURRENT AND EMERGING CHALLENGES IN ELECTRIC POWER SYSTEMS CRITICAL TO THE DEVELOPMENT OF SMART CITIES. PARTICIPANTS WILL ENGAGE IN SEVERAL INTEGRATED RESEARCH AREAS: MULTI-ENERGY SYSTEMS INTEGRATION, DATA-DRIVEN DECISION-MAKING USING ARTIFICIAL INTELLIGENCE, QUANTUM COMPUTING FOR ENERGY OPTIMIZATION, TRANSPORTATION ELECTRIFICATION, ELECTRIC GRID RESILIENCY AND CYBERSECURITY, ENERGY ECONOMICS, AND MODERN MICROGRID DESIGN. THESE TOPICS ARE STRATEGICALLY SELECTED TO CONFRONT URGENT ISSUES RELATED TO THE RELIABILITY, RESILIENCE, AND SECURITY OF ENERGY GENERATION, TRANSMISSION, AND DISTRIBUTION. THE PROGRAM WILL EMPLOY A COMBINATION OF SIMULATION, OPTIMIZATION, AND DATA ANALYTICS METHODS TO EXPLORE SOLUTIONS. THROUGH THIS PROJECT, STUDENTS WILL GAIN FOUNDATIONAL RESEARCH EXPERIENCE, CONTRIBUTE TO INNOVATIVE ENERGY SOLUTIONS, AND BE ENCOURAGED TO PURSUE GRADUATE STUDIES AND CAREERS IN STEM FIELDS THAT SUPPORT U.S. ENERGY INDEPENDENCE AND NATIONAL PROSPERITY. 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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

GOALI: DISTRIBUTED CONTROL, OPTIMIZATION AND STATE ESTIMATION OF NETWORKED MICROGRIDS WITH ENHANCED STABILITY

DEFINING THE THREE-DIMENSIONAL ORGANIZATION AND DYNAMICS OF HIV-1 ENVELOPE USING SUPERRESOLUTION MICROSCOPY

REU SITE: SUMMER ENGINEERING RESEARCH EXPERIENCES IN POWER AND ENERGY SYSTEMS FOR SMART CITIES

COLLABORATIVE RESEARCH: PREDICTING NOVEL INTERACTIONS BETWEEN PARASITIC BOTFLIES AND HIGH-ELEVATION DEER MICE UNDER CLIMATE CHANGE -ENVIRONMENTS AROUND THE GLOBE ARE RAPIDLY CHANGING, EXPOSING SPECIES TO NEW ENVIRONMENTAL CHALLENGES. TO UNDERSTAND THE EFFECTS THAT SHIFTING CLIMATES HAVE ON ORGANISMS, SCIENTISTS MUST INVESTIGATE HOW INDIVIDUALS RESPOND TO NEW ENVIRONMENTAL CHALLENGES, AND HOW THOSE RESPONSES ALTER SPECIES? DISTRIBUTIONS AND THEIR EVOLUTION. HIGH-ELEVATION, MONTANE ECOSYSTEMS (~2,500 METERS ABOVE SEA LEVEL) ARE ESPECIALLY VULNERABLE TO CLIMATE CHANGE, AND NUMEROUS HIGH-ELEVATION SPECIES HAVE EXPERIENCED CHANGES IN THEIR DISTRIBUTIONS OR HAVE GONE EXTINCT ALTOGETHER. THIS PROJECT WILL TEST WHETHER A FLESH MACROPARASITE, CUTEREBRA BOTFLIES, WILL EXPAND INTO HIGHER ELEVATIONS WITH A WARMING CLIMATE, AND WHETHER THIS EXPANSION WILL NEGATIVELY IMPACT HIGH-ELEVATION POPULATIONS OF ONE OF ITS HOSTS, THE NORTH AMERICAN DEER MOUSE (PEROMYSCUS MANICULATUS) THAT CURRENTLY DO NOT ENCOUNTER BOTFLIES. DATA FROM THIS PROJECT WILL BE USED TO DEVELOP NEW CURRICULA FOR MIDDLE SCHOOL STUDENTS FOCUSED ON ANALYZING AND INTERPRETING REAL DATA, AS WELL AS A SERIES OF YOUTUBE VIDEOS AIMED TO INCREASE UNDERSTANDING OF THE EFFECTS OF CLIMATE CHANGE ON BIODIVERSITY. THE VULNERABILITY OF HIGH-ELEVATION SPECIES MAY RESULT FROM THEIR GENERALLY NARROW RANGES AND THE UNRELENTINGLY STRONG ABIOTIC SELECTION PRESSURES INHERENT TO THESE ENVIRONMENTS, WHICH REDUCES A POPULATION?S GENETIC AND PHENOTYPIC VARIATION. AT ELEVATIONS NEAR SEA-LEVEL, INFECTIONS WITH BOTFLY LARVAE HAVE PRONOUNCED INFLUENCES ON DEER MOUSE PHYSIOLOGY, BUT NOT ON PERFORMANCE OR SURVIVAL. AT MODERATE ELEVATIONS HOWEVER (~2,000 METERS ABOVE SEA LEVEL), HOWEVER, BOTFLY INFECTIONS SEVERELY LIMIT PHYSIOLOGICAL FUNCTION, OVER-WINTER SURVIVAL AND THE ABILITY OF MICE TO PERFORM ECOLOGICALLY RELEVANT TASKS. THIS PROJECT WILL COMBINE FIELD PHYSIOLOGY ALONG A STEEP ELEVATIONAL GRADIENT (~SEA LEVEL TO >4,000 M ASL) WITH DEMOGRAPHIC MODELING, EXPERIMENTAL MANIPULATIONS, AND GENOME RE-SEQUENCING TO DETERMINE THE CONSEQUENCES OF ONGOING AND NOVEL INTERACTIONS BETWEEN BOTFLIES AND THEIR DEER MOUSE HOSTS ACROSS THEIR BROAD ELEVATIONAL RANGE. THE DATA WILL BE USED PREDICT FUTURE DEMOGRAPHIC CONSEQUENCES OF BOTFLY INFECTION ON DEER MOUSE POPULATIONS UNDER CLIMATE CHANGE. THE PROJECT WILL PROVIDE AN UNPRECEDENTED EXPLORATION OF HOST-PARASITE DYNAMICS IN THE FACE OF NOVEL INTERACTIONS AS A RESULT OF CLIMATE CHANGE. 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.

COLLABORATIVE RESEARCH: TRACING THE SPECTROPOLARIMETRIC HISTORY OF CIRCUMSTELLAR STRUCTURES FROM HIGH-MASS STARS THROUGH SUPERNOVAE

REGULATION OF GLUCAGON SECRETION BY MELANOCORTIN RECEPTOR-4

B CELL IMMUNITY IN EXPERIMENTALLY INDUCED ARTHRITIS

SOLAR COLLABORATIVE: PHOTONIC ENHANCEMENT OF ORGANIC PHOTOVOLTAICS TO ENABLE HIGHER EFFICIENCIES AND NOVEL MECHANISMS

MODULAR PHOTOASSISTED DIVERSITY-ORIENTED SYNTHESIS

AIR POLLUTION EXPOSURE AND EMERGING DEPRESSION RISK: TESTING THE ROLE OF PERIPHERAL INFLAMMATORY CYTOKINES DURING ADOLESCENCE - PROJECT SUMMARY DEPRESSION IS A PREVALENT, RECURRENT, AND FREQUENTLY CHRONIC DISORDER THAT AFFECTS APPROXIMATELY 21% OF INDIVIDUALS IN THEIR LIFETIME AND IS ASSOCIATED WITH SIGNIFICANT IMPAIRMENT AND CONSIDERABLE PUBLIC HEALTH BURDEN. TO ELUCIDATE FACTORS THAT CONTRIBUTE TO THE ONSET AND DEVELOPMENT OF DEPRESSIVE SYMPTOMS, THE CURRENT PROJECT SEEKS TO TEST THE ROLE OF ALTERATIONS IN PERIPHERAL CYTOKINES AS A BIOLOGICAL MEDIATOR OF ASSOCIATIONS BETWEEN AIR POLLUTION EXPOSURE AND DEPRESSIVE SYMPTOMS IN ADOLESCENTS. SPECIFICALLY, THE CURRENT PROJECT WILL UTILIZE A PROSPECTIVE LONGITUDINAL STUDY OF 120 ADOLESCENTS TO EXAMINE ASSOCIATIONS BETWEEN AIR POLLUTION EXPOSURE AND SUBSEQUENT TRAJECTORIES OF DEPRESSIVE SYMPTOMS AND IMMUNE MARKERS. THROUGH THE DIRECT ASSESSMENT OF THEORIZED BIOLOGICAL MEDIATORS, USE OF REPEATED ASSESSMENTS, AND CREATION OF SOPHISTICATED AIR POLLUTION EXPOSURE ESTIMATES, WE WILL OVERCOME PAST ROADBLOCKS TO PROGRESS AND RIGOROUSLY TEST A PUTATIVE MEDIATOR OF RISK. LEVERAGING STORED BLOOD SAMPLES COLLECTED AS PART OF AN ONGOING PARENT STUDY OF SOCIAL CONTRIBUTORS TO DEPRESSION DURING ADOLESCENCE, THIS WORK WILL CHARACTERIZE AIR POLLUTION EXPOSURE FOR STUDY PARTICIPANTS ACROSS MULTIPLE TIMESCALES (AIM 1), WHICH WILL THEN BE UTILIZED TO DETERMINE DOSE-RESPONSE ASSOCIATIONS BETWEEN AIR POLLUTION AND TRAJECTORIES OF DEPRESSIVE SYMPTOMS ACROSS A 6-MONTH PERIOD (AIM 2). LASTLY, IT WILL PROBE PERIPHERAL IMMUNE MARKERS AS PUTATIVE MEDIATIONS BETWEEN AIR POLLUTION AND DEPRESSIVE SYMPTOMS, TESTING COMPETING MODELS OF CYTOKINES (E.G., PROINFLAMMATORY, TH-1, AND TH-2) TO DETERMINE THE SPECIFICITY OF THE IMMUNE MARKERS IN RELATION TO RISK. THROUGH THIS METHODOLOGICALLY RIGOROUS APPROACH, WE WILL BE POISED TO CONDUCT STRONG TESTS OF DIRECTIONAL ASSOCIATIONS BETWEEN AIR POLLUTION EXPOSURE AND DEPRESSIVE SYMPTOMS AND TO IDENTIFY IMMUNOLOGICAL PARAMETERS THAT MAY MEDIATE RISK. IN DOING SO, INSIGHTS FROM THIS PROJECT WILL CRITICALLY INFORM FUTURE HYPOTHESES TO ELUCIDATE BIOLOGICAL AND PSYCHOLOGICAL CASCADES THAT CONTRIBUTE TO THE ADVERSE EFFECTS OF AIR POLLUTION EXPOSURE ON MENTAL HEALTH TO IDENTIFY NOVEL TARGETS FOR INTERVENTION EFFORTS AND ULTIMATELY REDUCE THE SIGNIFICANT BURDENS ASSOCIATED WITH DEPRESSION.

MECHANISMS OF BASEMENT MEMBRANE REGULATION DURING ANGIOGENESIS

EXCITED STATE INTRAMOLECULAR PROTON TRANSFER-BASED PHOTOASSISTED METHODOLOGIES TO ACCESS COMPLEX MOLECULAR ARCHITECTURES

COLLABORATIVE RESEARCH: SUPERINVADERS: TESTING A GENERAL HYPOTHESIS OF FOREST INVASIONS BY WOODY SPECIES ACROSS THE AMERICAS -INVASIVE PLANT SPECIES ARE A FORM OF BIOLOGICAL POLLUTION THAT COST BILLIONS OF DOLLARS EACH YEAR IN LOST CROP AND TIMBER PRODUCTION, AND THEY ARE ONE OF THE PRINCIPAL THREATS TO NATIVE BIODIVERSITY. EFFECTIVE MANAGEMENT OF INVASIVE SPECIES REQUIRES THAT SCIENTISTS UNDERSTAND HOW THEY COMPETE SUCCESSFULLY WITH NATIVE SPECIES. ONE OF THE LEAST UNDERSTOOD BEHAVIORS OF INVASIVE PLANTS IS THAT A SINGLE INVASIVE SPECIES CAN DOMINATE IN MANY DIFFERENT TYPES OF ENVIRONMENTS. IN PARTICULAR, SCIENTISTS HAVE IDENTIFIED A GROUP OF ?SUPERINVADERS? THAT, COUNTER TO WHAT IS EXPECTED FOR NATIVE SPECIES, CAN GROW VERY FAST IN SUNLIGHT BUT ALSO TOLERATE HEAVY SHADE IN THE FOREST UNDERSTORY. ALTHOUGH THERE IS GOOD EVIDENCE THAT THIS BEHAVIOR DRIVES THEIR INCREASING ABUNDANCE IN BOTH TEMPERATE AND TROPICAL FORESTS, SCIENTISTS DON?T UNDERSTAND HOW THIS OCCURS: WHY SHOULD INVASIVE SPECIES PLAY BY DIFFERENT RULES THAN NATIVE SPECIES IN THE SAME ENVIRONMENT? ONE HYPOTHESIS IS THAT INVASIVE SPECIES HAVE FEWER PESTS THAN NATIVE SPECIES, AND THIS ADVANTAGE ALLOWS THEM TO PERSIST IN STRESSFUL ENVIRONMENTS. IN THIS PROJECT, ECOLOGISTS WILL EXPERIMENTALLY TEST THIS IDEA IN MANY DIFFERENT TYPES OF FORESTS TO DETERMINE HOW THIS ?SUPERINVADER? BEHAVIOR EMERGES. MOREOVER, BY LINKING HOW PLANTS SIMULTANEOUSLY RESPOND TO PESTS AND ENVIRONMENTAL STRESS, SCIENTISTS WILL BETTER UNDERSTAND HOW SPECIES COEXIST TO FOSTER NATIVE BIODIVERSITY. THE PROJECT WILL TRAIN TWO US DOCTORAL STUDENTS, ONE POSTDOCTORAL SCHOLAR AND NUMEROUS UNDERGRADUATE STUDENTS. THE PROJECT WILL FOSTER INTERNATIONAL COLLABORATION, RESEARCH PARTNERSHIPS AND KNOWLEDGE TRANSFER ACROSS THE AMERICAS. THIS WILL BENEFIT US SCIENTISTS, DOCTORAL STUDENT TRAINEES AND POSTDOCTORAL SCHOLAR. A NEW RESEARCH EXPERIENCE FOR UNDERGRADUATES PROGRAM AT THE UNIVERSITY OF SOUTH CAROLINA AND A SUMMER WORKSHOP IN PUERTO RICO WILL CONTRIBUTE TO BROADENING PARTICIPATION BY UNDERGRADUATE STUDENTS FROM GROUPS UNDER-REPRESENTED IN SCIENCE AND TECHNOLOGY. THE POSTDOCTORAL SCHOLAR WILL LEAD AN EFFORT TO CREATE A FOREST SUPERINVADER NETWORK THAT WILL INCREASE THE SCOPE OF THIS PROJECT TO THE GLOBAL LEVEL TO FACILITATE INTERNATIONAL KNOWLEDGE TRANSFER AND MORE EFFECTIVE FOREST AND LAND MANAGEMENT WORLDWIDE THROUGH BETTER UNDERSTANDING OF PLANT INVASION MECHANISMS. THE PROJECT INVOLVES TWO COMPONENTS. IN THE FIRST, RESEARCH TEAMS WILL MONITOR THE GROWTH AND SURVIVAL OF NATIVE AND INVASIVE TREE SAPLINGS ACROSS LIGHTS GRADIENTS IN 10 LOCATIONS ACROSS THE AMERICAS, INCLUDING TEMPERATE FORESTS IN CONNECTICUT AND SOUTH CAROLINA, TROPICAL FORESTS IN MEXICO, COSTA RICA, AND THE CARIBBEAN, AND SUBTROPICAL FORESTS IN SOUTHERN BRAZIL. USING FIELD MEASUREMENTS OF METABOLIC ACTIVITY OF DIFFERENT TISSUES ABOVE- AND BELOWGROUND, RESEARCHERS WILL TEST THE HYPOTHESIS THAT LOWER ENERGY COSTS IN INVADERS, AS A RESULT OF FEWER PESTS, ALLOWS THESE INVADERS TO CIRCUMVENT FUNCTIONAL TRADEOFFS TYPICALLY ASSOCIATED WITH FAST GROWTH AND SHADE TOLERANCE. IN A SECOND COMPONENT CONDUCTED IN FIVE LOCATIONS, RESEARCHERS WILL EXPERIMENTALLY REMOVE INSECTS AND FUNGAL PATHOGENS FROM NATIVE AND INVASIVE SAPLINGS TO TEST WHETHER SHADE TOLERANCE IS DRIVEN BY PEST LOADS. IN BOTH COMPONENTS, RESEARCHERS WILL BUILD AND TEST INTEGRATIVE MODELS OF PLANT BEHAVIOR THAT CONSIDER THE ENERGETIC COSTS OF SEEMINGLY DISPARATE BEHAVIORS (E.G., RESOURCE CAPTURE VERSUS DEFENSE) TO FURTHER SCIENTIFIC UNDERSTANDING OF CRITICAL LINKAGES BETWEEN PLANT FUNCTIONAL ECOLOGY AND POPULATION DYNAMICS. 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.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

IDENTIFYING DETERMINANTS OF HIV-1 RESPONSIBLE FOR THE NANOSCALE DISTRIBUTION AND DYNAMICS OF VIRUS ASSEMBLY - PROJECT SUMMARY. HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) ASSEMBLY MECHANISMS, NAMELY THE ACQUISITION OF THE ENVELOPE GLYCOPROTEIN (ENV) INTO THE ASSEMBLING VIRAL LATTICE, REMAINS INADEQUATELY UNDERSTOOD. THE CONTINUED INNOVATION OF TOOLS TO INTERROGATE THESE MOLECULAR AND NANOSCALE ASSEMBLY PROCESSES IS BEGINNING TO DISCLOSE SOME OF THE BASIC PRINCIPLES. THIS PROPOSAL AIMS TO BUILD UPON THESE INNOVATIONS AND QUANTIFY THE REQUIREMENTS FOR ENV ASSEMBLY BY INTERROGATING VIRAL AND HOST FACTOR DETERMINANTS REGULATING INTRACELLULAR TRAFFICKING, SURFACE DISPLAY, VIRUS INCORPORATION, AND CELL-TO-CELL SPREAD. TO ACCOMPLISH THESE AIMS, WE WILL ADAPT CURRENT SUPERRESOLUTION AND SINGLE-MOLECULE TRACKING APPROACHES DEVELOPED BY OUR LABORATORY TO UNDERSTAND THE THREE-DIMENSIONAL STRUCTURAL ORGANIZATION AND SPATIOTEMPORAL DYNAMICS OF ENV THROUGHOUT ASSEMBLY STAGES AND CELL-TO-CELL SPREAD. NEXT, WE WILL DISSECT THE LONG ENV CYTOPLASMIC TAIL TO UNDERSTAND WHICH RESIDUES/REGIONS DRIVE ENV INCORPORATION. FINALLY, WE PROPOSE TO UTILIZE GENETIC KNOCK-OUT TO UNDERSTAND THE ROLE OF IDENTIFIED HOST TRAFFICKING FACTORS IN REGULATING THE SURFACE LEVELS OF ENV. OUR PRELIMINARY DATA SUPPORTS THE FEASIBILITY OF OUR APPROACH BY DEMONSTRATING OUR ABILITY TO EXTRACT QUANTITATIVE INFORMATION REGARDING THE NANOSCALE ORGANIZATION AND SINGLE-MOLECULE DYNAMICS OF ENV IN THREE-DIMENSIONS. THESE COLLECTIVE APPROACHES WILL SHED NEW LIGHT ON HIV-1 ASSEMBLY AND CELL-TO-CELL VIRUS TRANSFER, INFORMING NEW MODELS AND APPROACHES AIMED AT TARGETING THESE PROCESSES THERAPEUTICALLY.

QUANTIFYING FLUCTUATIONS TO BUILDPREDICTIVE MODELS AND GUIDE DESIGN OF GENE NETWORKS

PHOTOLABILE REPORTERS OF MOLECULAR RECOGNITION: CAGING, TAGGING AND PHOTOAMPLIFICATION