Merrimack College

INSTITUTIONAL PORTION OF CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND

MERRIMACK COLLEGE HIGHER EDUCATION EMERGENCY RELIEF FUND

EVALUATION OF A DISTRICT-WIDE INITIATIVE TO IMPROVE SCHOOL MEAL CONSUMPTION AND PHYSICAL ACTIVITY LEVELS AMONG ELEMENTARY STUDENTS IN ANCHORAGE, ALASKA - PROJECT SUMMARY IMPROVING CHILDREN’S DIETS AND PHYSICAL ACTIVITY LEVELS ARE KEY STRATEGIES TO REDUCE THE RISK OF OBESITY. HOWEVER, MOST CHILDREN DO NOT MEET DIETARY OR PHYSICAL ACTIVITY RECOMMENDATIONS, AND CHILDREN WHO ARE FROM FAMILIES WITH SOCIOECONOMIC DISADVANTAGES AND/OR WHO ARE RACIAL/ETHNIC MINORITIES EXPERIENCE DISPROPORTIONATELY HIGHER RATES OF OBESITY, WITH ALASKA NATIVE/AMERICAN INDIAN CHILDREN EXPERIENCING THE HIGHEST RATES NATIONALLY. SCHOOLS CAN BE AN IDEAL LOCATION TO PROMOTE HEALTHIER HABITS AS CHILDREN SPEND A SUBSTANTIAL PORTION OF THEIR TIME IN SCHOOL AND OFTEN CONSUME UP TO HALF THEIR DAILY ENERGY INTAKE THERE. TWO PROMISING, COST-EFFECTIVE SCHOOL POLICIES ARE LONGER LUNCH PERIODS AND LONGER RECESS WITH INTEGRATED PA OPPORTUNITIES, BUT RIGOROUS EVIDENCE IS LACKING. IN THIS TIME-SENSITIVE PROPOSAL, WE PROPOSE TO EVALUATE A NATURAL EXPERIMENT IN ANCHORAGE, ALASKA OF THE IMPLEMENTATION OF A WELLNESS INITIATIVE IN ELEMENTARY SCHOOLS THAT INCLUDES 30 MINUTE LUNCH PERIODS AND 54 MINUTES OF PA DAILY (INCLUDING 30 MINUTES OF RECESS IN ADDITION TO CLASSROOM MOVEMENT ACTIVITIES). THE WELLNESS INITIATIVE WILL HAVE A STAGGERED ROLLOUT IN SCHOOLS OVER THE SPAN OF FOUR YEARS. OUR STUDY WILL COLLECT LONGITUDINAL DATA FROM 4,000 STUDENTS IN K-4TH GRADE TO ASSESS CHANGES IN SCHOOL MEAL CONSUMPTION USING PLATE WASTE METHODOLOGY (AIM 1). PHYSICAL ACTIVITY LEVELS WILL ALSO BE ASSESSED IN A SUBSAMPLE OF CHILDREN (N=2,000 STUDENTS IN GRADES K-4) USING ACCELEROMETER MEASUREMENTS (AIM 2). OUTCOMES WILL BE MEASURED AT BASELINE AND POST-IMPLEMENTATION THE FOLLOWING SCHOOL YEAR (COLLECTED DURING THE SAME MONTH AT EACH TIME POINT). ADDITIONALLY, BMI, SLEEP DURATION AND QUALITY, AND OTHER FACTORS RELATED TO ACADEMIC PERFORMANCE (I.E., CHANGES IN STUDENTS’ DISRUPTIVE CLASSROOM BEHAVIORS [MEASURED AT BASELINE AND ONE YEAR POST-IMPLEMENTATION], DISCIPLINARY REFERRALS TO THE PRINCIPAL, HUNGER-RELATED VISITS TO THE SCHOOL NURSE, AND STANDARDIZED TEST SCORES [BASELINE AND UP TO FOUR YEARS POST-IMPLEMENTATION]) WILL BE EVALUATED. IMPLEMENTATION FIDELITY WILL BE ASSESSED THROUGHOUT THE STUDY PERIOD VIA SITE VISITS, ENVIRONMENTAL SCANS, AND TEACHER SURVEYS. ANCHORAGE SCHOOL DISTRICT PLANS THE STAGGERED IMPLEMENTATION OF THE INITIATIVE TO BEGIN IN THE 2021-22 SCHOOL YEAR. THUS, TIME- SENSITIVE FUNDING IS CRITICAL TO ENSURE ADEQUATE TIME FOR BASELINE DATA COLLECTION. THE PROPOSAL’S SIGNIFICANCE LIES IN OUR ABILITY TO PROVIDE THE FIRST EMPIRICAL EVIDENCE OF THE DEGREE TO WHICH SCHOOL POLICIES FOR LONGER LUNCH PERIODS AND INTEGRATED PHYSICAL ACTIVITY OPPORTUNITIES INFLUENCE STUDENTS’ DIETARY INTAKES, PHYSICAL ACTIVITY LEVELS, WEIGHT STATUS, AND FACTORS RELATED TO ACADEMIC PERFORMANCE. THIS RIGOROUS, INNOVATIVE, AND TIME-SENSITIVE STUDY WILL CONTRIBUTE TO THE DEVELOPMENT OF A COMPREHENSIVE EVIDENCE BASE ON THE POTENTIAL EFFECTIVENESS OF SCHOOL NUTRITION AND PHYSICAL ACTIVITY POLICIES, WHICH CAN HELP TO ADDRESS HEALTH DISPARITIES IN CHILDREN, INCLUDING AMONG AN UNDERSERVED AND UNDERSTUDIED ALASKA NATIVE POPULATION. STUDY RESULTS WILL ALSO PROVIDE ESSENTIAL EVIDENCE TO INFORM LOCAL, STATE, AND FEDERAL POLICYMAKERS’ DECISIONS REGARDING SCHOOL NUTRITION AND PHYSICAL ACTIVITY POLICIES AS WELL AS HAVE THE STRONG POTENTIAL TO IMPACT CHILDREN’S HEALTH MORE BROADLY.

EVALUATION OF THE UPDATED FEDERAL NUTRITION STANDARDS FOR SCHOOL MEALS - PROJECT SUMMARY IN THE UNITED STATES (U.S.), APPROXIMATELY 1 IN 5 CHILDREN HAVE OBESITY, AND CHILDREN WHO ARE FROM FAMILIES WITH SOCIOECONOMIC DISADVANTAGES AND/OR WHO ARE RACIAL/ETHNIC MINORITIES EXPERIENCE DISPROPORTIONATELY HIGHER RATES OF OBESITY. WHILE HEALTHIER DIETARY PATTERNS ARE ASSOCIATED WITH THE PREVENTION AND/OR TREATMENT OF OBESITY, FEW CHILDREN MEET DIETARY RECOMMENDATIONS. THEREFORE, POLICIES THAT IMPROVE CHILDREN’S DIETARY INTAKES WHILE ADDRESSING DISPARITIES BY RACE/ETHNICITY AND SOCIOECONOMIC STATUS ARE CRITICAL. IN APRIL 2024, THE UNITED STATES DEPARTMENT OF AGRICULTURE (USDA) ANNOUNCED MAJOR UPDATES TO THE NUTRITIONAL STANDARDS FOR THE NATIONAL SCHOOL LUNCH PROGRAM AND SCHOOL BREAKFAST PROGRAM, WHICH FEED OVER 30 MILLION CHILDREN EACH SCHOOL DAY (WITH THE MAJORITY OF THESE CHILDREN COMING FROM LOW-INCOME HOUSEHOLDS AND RECEIVING FREE OR REDUCED-PRICED SCHOOL MEALS). THESE STANDARDS BETTER ALIGN SCHOOL MEALS WITH THE 2020-2025 DIETARY GUIDELINES FOR AMERICANS (DGAS). THEY INCLUDE, FOR THE FIRST TIME IN HISTORY, A LIMIT ON ADDED SUGARS IN SCHOOL MEALS, AS WELL AS STRONGER SODIUM LIMITS. EVALUATING THE IMPACT OF THESE UPDATED STANDARDS— INCLUDING SCHOOL MEAL COMPLIANCE, PRODUCT REFORMULATION, SCHOOL MEAL PARTICIPATION, STUDENT DIET QUALITY AND DIETARY DISPARITIES, AND CHILDREN’S BMI— CAN MAKE A SIGNIFICANT CONTRIBUTION TO THE FIELD AND INFORM FUTURE OPPORTUNITIES TO FURTHER STRENGTHEN SCHOOL MEAL NUTRITIONAL STANDARDS. THUS, IN THIS TIME-SENSITIVE PROPOSAL, WE PROPOSE TO EVALUATE THE IMPACT OF THESE UPDATED NUTRITIONAL STANDARDS. OUR STUDY WILL FIRST EXAMINE COMPLIANCE WITH THE NEW STANDARDS AND POTENTIAL PRODUCT REFORMULATION USING 3 MONTHS OF DETAILED MENU DATA (E.G., PRODUCTION RECORDS, RECIPES, AND NUTRITION LABELS) FROM 24 SCHOOLS ACROSS 4 STATES BEFORE AND AFTER IMPLEMENTATION OF THE UPDATED STANDARDS (AIM 1). NEXT, WE WILL EXAMINE THE IMPACT OF THE UPDATED STANDARDS ON SCHOOL MEAL PARTICIPATION RATES BY ANALYZING SCHOOL-LEVEL, STATE-WIDE SCHOOL MEAL PARTICIPATION DATA ANNUALLY FROM N=14 STATE CHILD NUTRITION PROGRAMS (AIM 2). THIRD, WE WILL EXAMINE THE IMPACT OF THE UPDATED STANDARDS ON STUDENTS’ DIETARY INTAKES BY COLLECTING PRE- AND POST-POLICY PLATE WASTE MEASUREMENTS FROM N=2,400 ELEMENTARY STUDENTS AT N= 24 SCHOOLS ACROSS 4 STATES FOR BREAKFAST AND LUNCH (AIM 3). LASTLY, AS AN EXPLORATORY AIM, WE WILL EXAMINE THE IMPACT OF THE UPDATED STANDARDS ON BMI USING DATA FROM A NATIONALLY REPRESENTATIVE SAMPLE OF SCHOOL-AGED CHILDREN. THE NEW STANDARDS BEGIN A PHASED IMPLEMENTATION STARTING JULY 1, 2025. WITHOUT FUNDING IN THIS ROUND, WE WILL MISS THE ONLY OPPORTUNITY TO COLLECT BASELINE DATA AND WE WILL BE UNABLE TO CONDUCT A RIGOROUS EVALUATION OF THIS NEW NATIONAL POLICY. THIS WILL BE THE FIRST STUDY TO PROVIDE EMPIRICAL EVIDENCE ON THE IMPACT OF A NATIONAL SCHOOL MEAL POLICY TO LIMIT ADDED SUGARS AND REDUCE SODIUM LEVELS TO ALIGN MORE CLOSELY WITH THE DGAS. OVERALL, THIS STUDY IS A UNIQUE OPPORTUNITY TO EVALUATE A POTENTIALLY HIGH-IMPACT NATIONAL POLICY TO IMPROVE SCHOOL MEALS FOR MILLIONS OF CHILDREN, AND MAY INFORM BEST PRACTICES WITH THE POLICY’S PHASED IMPLEMENTATION AS WELL AS FUTURE SCHOOL MEAL POLICIES AT THE LOCAL, STATE, AND NATIONAL LEVELS.

FINANCIAL, ACADEMIC, SOCIAL, AND MENTAL HEALTH SUPPORTS TO IMPROVE STEM UNDERGRADUATE STUDENT RETENTION AND GRADUATION

MITOCHONDRIAL AGING PROMOTES INFLAMMATION - ABSTRACT: MITOCHONDRIAL AGING PROMOTES INFLAMMATION AGING IS OFTEN ASSOCIATED WITH A PROGRESSIVE DECLINE IN HEALTH RESULTING IN A DECLINE IN THE QUALITY OF LIFE THAT LIMITS HEALTHSPAN, DEFINED AS NUMBER OF YEARS SPENT IN GOOD HEALTH. ONE CRITICAL GOAL OF AGING RESEARCH IS TO INCREASE “HEALTHSPAN”. THIS GOAL IS ESPECIALLY IMPORTANT BECAUSE ACCORDING TO CDC, THE NUMBER OF US ADULTS AGED >65 OR OLDER WILL MORE THAN DOUBLE TO APPROXIMATELY 71 MILLION BY THE YEAR 2030, AND PRESENT HEALTHSPAN DATA PROJECT AN UNTENABLE DRAIN ON OUR HEALTHCARE SYSTEM IN ADDITION TO THE OBVIOUS PERSONAL BURDEN. OF THE MANY CELLULAR PROCESSES THAT DECLINE WITH AGE, MITOCHONDRIAL DYSFUNCTION IS ESPECIALLY IMPORTANT BECAUSE NUMEROUS STUDIES SHOW A LINK BETWEEN FAILING MITOCHONDRIA AND THE DEVELOPMENT OF AGE-ASSOCIATED DISEASES. THIS PROPOSED PROJECT WILL EVALUATE AGE ASSOCIATED MITOCHONDRIAL TRANSLOCATION OF STAT3(MITOSTAT3) AS THE DRIVER OF AN ABERRANT ADDICTIVE DEPENDENCE OF AGING CD4+ T CELLS ON OXIDATIVE PHOSPHORYLATION(OXPHOS) AND IMPAIRED UPREGULATION OF THE AEROBIC GLYCOLYSIS TO PROMOTE INFLAMMATION. OUR DATA SHOWS THAT CD4+ T CELLS FROM LEAN NORMOGLYCEMIC OLDER ADULTS (AVG AGE 62 YRS) PRODUCE HIGHER AMOUNTS OF PROINFLAMMATORY TH17 CYTOKINES COMPARED TO CELLS FROM LEAN NORMOGLYCEMIC YOUNGER ADULTS (AVG AGE 32 YRS). WE EXPERIMENTALLY ESTABLISHED THAT THIS PROINFLAMMATORY PROFILE WAS SECONDARY TO AN ABERRANT MITOCHONDRIAL RESPIRATORY PROFILE, LOWER GLYCOLYSIS AND IMPAIRMENT IN AUTOPHAGY, THE CELLULAR RECYCLING PROCESS KNOWN TO DECLINE WITH AGE. WE OBSERVED THAT T CELLS FROM OLDER SUBJECTS HAD HIGHER MITOSTAT3, WHICH IS KNOWN TO DRIVE OXPHOS DEPENDENCE IN MANY CELL TYPES. WE ALSO OBSERVED THAT MITOCHONDRIAL TRANSLOCATION OF STAT3 OCCURRED IN AN AUTOPHAGY DEPENDENT MANNER. GENETIC INHIBITION OF AUTOPHAGY IN T CELLS FROM YOUNGER SUBJECTS, PROMOTED MITOCHONDRIAL TRANSLOCATION OF STAT3, RESULTING IN A BIOENERGETIC AND INFLAMMATORY PROFILE THAT MIMICKED THAT OF AGING T CELLS. HYPOTHESIS: PREVENTING AGING INDUCED MITOCHONDRIAL TRANSLOCATION OF STAT3 IMPROVES T CELL FUNCTION AND ALLEVIATES INFLAMMATION. WE WILL UTILIZE THE NEWLY DEVELOPED SMALL MOLECULE INHIBITORS OF MITOSTAT3 TO EITHER DIRECTLY INHIBIT MITOCHONDRIAL TRANSLOCATION OF STAT3 OR INDIRECTLY BY PROMOTING AUTOPHAGY AND THEREBY LIMIT MITOSTAT3. WE HYPOTHESIZE THAT THE METABOLIC REPROGRAMMING PROMOTED BY LIMITING MITOSTAT3, WOULD RESULT IN HIGHER GLYCOLYSIS AND LOWER OXPHOS DEPENDENCE, IMPROVED T CELLS FUNCTION AND WOULD ALLEVIATE INFLAMMATION. WE WILL ESTABLISH CAUSE AND EFFECT BY MANIPULATING MITOSTAT3 USING GENETIC AND PHARMACOLOGICAL GAIN-AND-LOSS OF FUNCTION APPROACHES. THIS MECHANISTIC WORK WILL MAP THE ROLE OF MITOSTAT3 IN THE REGULATION OF T CELL METABOLISM AND INFLAMMATION DURING AGING AND HAS THERAPEUTIC IMPLICATIONS TOWARDS THE GOAL OF IMPROVING HEALTH SPAN. .

THE INFLUENCE OF QUICK-SERVICE RESTAURANTS ON CHILDREN'S DIETS

CAREER: DISSECTING THE MOLECULAR REGULATION OF SEPTIN-MEDIATED PLANT INVASION BY THE BLAST FUNGUS MAGNAPORTHE ORYZAE -THIS AWARD IS FUNDED IN WHOLE OR IN PART UNDER THE AMERICAN RESCUE PLAN ACT OF 2021 (PUBLIC LAW 117- 2) THE FUNGUS MAGNAPORTHE ORYZAE CAUSES A HIGHLY DESTRUCTIVE DISEASE OF CULTIVATED RICE AND WHEAT, CALLED BLAST, WHICH POSES AN ONGOING THREAT TO FOOD SECURITY AROUND THE WORLD. IN THE FIELD, BLAST IS COMBATTED USING A LIMITED RANGE OF FUNGICIDES, AND THE EMERGENCE OF RESISTANCE TO THESE CHEMISTRIES IS A LOOMING THREAT. THUS, THERE IS AN URGENT NEED TO DEVELOP NEW STRATEGIES TO CONTROL BLAST, BUT THIS DEMANDS A MORE COMPLETE MECHANISTIC UNDERSTANDING OF M. ORYZAE INFECTION BIOLOGY. TO INFECT PLANTS, M. ORYZAE PRODUCES A SPECIALIZED PRESSURE-GENERATING INFECTION CELL, CALLED AN APPRESSORIUM, WHICH IT USES TO BREAK INSIDE OF LEAVES. THIS RESEARCH FOCUSES ON GAINING A BETTER UNDERSTANDING OF HOW THESE INFECTION CELLS ARE BUILT AND HOW THEY WORK, AND THEREFORE THE OUTCOMES MAY HELP TO SAFEGUARD GLOBAL FOOD SECURITY AND ENHANCE AGRICULTURAL PRODUCTIVITY. THE PROPOSED ACTIVITIES WILL PROVIDE IMPROVED TRAINING AND EDUCATION IN BIOIMAGING FOR THE STUDY OF PLANTS, MICROBES AND THEIR INTERACTIONS, AND WILL PROVIDE ENHANCED OPPORTUNITIES FOR LOW-INCOME, AND FIRST-GENERATION HIGH SCHOOL STUDENTS TO GAIN HANDS-ON RESEARCH EXPERIENCE IN CUTTING-EDGE FUNGAL CELL BIOLOGY, THEREIN PROMOTING THEIR PARTICIPATION IN HIGHER-EDUCATION AND SCIENCE. COMMUNICATION OF THESE RESEARCH OUTCOMES AT LOCAL EVENTS WILL PROVIDE ENHANCED OPPORTUNITIES FOR PUBLIC ENGAGEMENT, LEADING TO INCREASED SCIENTIFIC LITERACY AND AWARENESS AND GREATER TRUST IN SCIENCE AND SCIENTISTS. APPRESSORIUM-MEDIATED PLANT INVASION BY M. ORYZAE REQUIRES THE REGULATED ASSEMBLY OF A TOROIDAL RING STRUCTURE, COMPOSED OF A CLASS OF CYTOSKELETAL FILAMENT-FORMING GTP-BINDING PROTEINS CALLED SEPTINS, WITHIN ITS BASE. HOW THIS INFECTION-SPECIFIC SEPTIN RING FORMS IN THE RIGHT PLACE, AND AT THE RIGHT TIME, WITHIN THE DEVELOPING APPRESSORIUM TO ENABLE PLANT INVASION, REMAINS LARGELY MYSTERIOUS. INDEED, UNDERSTANDING HOW SEPTINS ARE ASSEMBLED AND DYNAMICALLY REMODELED INTO DIFFERENT FUNCTIONAL ARCHITECTURES IN DIVERSE CELL TYPES IS A CURRENT FRONTIER IN THE FIELD. CRITICALLY, IMPROVED MECHANISTIC UNDERSTANDING OF SEPTIN RING ASSEMBLY AND FUNCTION IN M. ORYZAE MAY INFORM THE DEVELOPMENT OF NEW FUNGICIDES TO CONTROL BLAST, AND OTHER FUNGAL CROP DISEASES, ESPECIALLY GIVEN THAT PLANTS DO NOT CONTAIN SEPTINS. THE GOALS OF THIS PROJECT ARE TO GAIN NEW INSIGHT INTO THE MOLECULAR MECHANISMS BY WHICH INCIPIENT SEPTIN DISC-LIKE STRUCTURES FORM IN THE BASE OF APPRESSORIA AND ARE REMODELED INTO RINGS, AND HOW THESE CORTICAL STRUCTURES ORGANIZE THE PENETRATION INTERFACE FOR PLANT INVASION. THIS PROJECT COMBINES THE USE OF TIME-RESOLVED PROXIMITY PROTEOMICS, LIVE CELL IMAGING, AND REVERSE GENETICS TO FUNCTIONALLY MAP THE SEPTIN-ORGANIZED APPRESSORIUM BASAL CORTEX AND PENETRATION INTERFACE AND EMPLOYS A NOVEL FLUORESCENCE MICROSCOPY-BASED GENOME-WIDE CHEMICAL MUTAGENESIS SCREEN TO IDENTIFY NOVEL REGULATORS OF SEPTIN RING ASSEMBLY. 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 ROLE OF NEUROTROPHINS IN CHRONIC PELVIC PAIN AND CENTRAL SENSITIZATION AMONG ADOLESCENTS AND WOMEN WITH ENDOMETRIOSIS - PROJECT SUMMARY/ABSTRACT ENDOMETRIOSIS IS A COMMON DISEASE AMONG REPRODUCTIVE-AGED ADOLESCENTS AND WOMEN AND CAN LEAD TO DEBILITATING PELVIC PAIN, INFERTILITY, REDUCED QUALITY OF LIFE AND SIGNIFICANT HEALTH CARE COSTS. WHILE SOME PATIENTS WITH ENDOMETRIOSIS WILL REMAIN ASYMPTOMATIC OR THEIR SYMPTOMS WILL BE MANAGED WITH EMPIRICAL TREATMENT, APPROXIMATELY 30% OF WOMEN UNDERGOING LAPAROSCOPIC SURGERY FOR ENDOMETRIOSIS WILL HAVE TREATMENT-RESISTANT CHRONIC PELVIC PAIN, MEANING THAT WHILE THEIR ENDOMETRIOTIC LESIONS HAVE BEEN EXCISED THEY WILL NOT EXPERIENCE PAIN REMEDIATION. ONE POTENTIAL FACTOR LEADING TO THE DEVELOPMENT OF CHRONIC PELVIC PAIN AMONG ENDOMETRIOSIS PATIENTS IS THROUGH CENTRAL SENSITIZATION RESULTING FROM CHANGES IN THE CENTRAL NERVOUS SYSTEM THAT AMPLIFY PAINFUL STIMULI. HOWEVER, VERY FEW STUDIES HAVE ASSESSED CENTRAL SENSITIZATION AMONG WOMEN WITH ENDOMETRIOSIS AND NONE HAVE ASSESSED IT AMONG ADOLESCENTS. AMONG ENDOMETRIOSIS PATIENTS, GREATER INNERVATION OF ENDOMETRIOTIC LESIONS IS ASSOCIATED WITH GREATER ENDOMETRIOSIS-RELATED PAIN AND THESE PAIN LEVELS MAY BE FURTHER AMPLIFIED BY THE PRO-INFLAMMATORY ENVIRONMENT WITHIN THE PERITONEAL CAVITY. AMONG OTHER CHRONIC PAIN CONDITIONS, TWO NERVE GROWTH FACTORS (NEUROTROPHINS) - SS-NERVE GROWTH FACTOR (SS-NGF) AND BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) ARE THOUGHT TO BE INVOLVED IN THE DEVELOPMENT OF CENTRAL SENSITIZATION. LIMITED RESEARCH HAS ASSESSED THE RELATIONSHIP BETWEEN NEUROTROPHINS WITHIN THE PERITONEAL CAVITY AND PAIN SYMPTOMS AMONG ENDOMETRIOSIS PATIENTS, AND NO STUDIES HAVE PROSPECTIVELY ASSESSED THE PERITONEAL FLUID LEVELS OF NEUROTROPHINS IN ADDITION TO INFLAMMATORY MARKERS AT SURGERY WITH POST-SURGERY PAIN SYMPTOMS. OUR PROPOSAL FILLS THIS SCIENTIFIC GAP BY INVESTIGATING WHETHER PERITONEAL FLUID LEVELS OF SS-NGF AND BDNF ARE (1) ASSOCIATED WITH CO-MORBID PAIN CONDITIONS (E.G. MIGRAINE, FIBROMYALGIA) AMONG ENDOMETRIOSIS PATIENTS, AND (2) DIFFERENTIATE BETWEEN ENDOMETRIOSIS PATIENTS WHO WILL EXPERIENCE PAIN REMEDIATION AFTER SURGERY AND THOSE WHO WILL NOT AND IF THIS ASSOCIATION IS MODIFIED BY THE INFLAMMATORY ENVIRONMENT IN THE PERITONEAL CAVITY. ADDITIONALLY, IN EXPLORATORY ANALYSES, WE WILL ASSESS THE ASSOCIATION BETWEEN NEUROTROPHIN LEVELS IN THE PERITONEAL CAVITY AND MEASURES OF UNDERLYING PAIN SENSITIVITY AS MARKERS OF CENTRAL SENSITIZATION – THE FIRST STUDY TO DATE TO LOOK AT THESE ASSOCIATIONS AMONG ENDOMETRIOSIS PATIENTS. COLLECTIVELY, THESE AIMS HAVE THE POTENTIAL TO ADVANCE OUR UNDERSTANDING OF CHRONIC PELVIC PAIN AND CENTRAL SENSITIZATION AMONG ADOLESCENTS AND WOMEN WITH ENDOMETRIOSIS – LAYING IMPORTANT FOUNDATIONAL WORK IN FURTHERING OUR EFFORTS TO PROVIDE SUCCESSFUL PERSONALIZED, PRECISION MEDICINE TO MAXIMIZE PAIN REMEDIATION. SUCCESS WILL REDUCE HEALTH CARE COSTS AND INCREASE LONG-TERM HEALTH AND QUALITY OF LIFE FOR ADOLESCENTS AND WOMEN WITH ENDOMETRIOSIS.

FOUNDATIONS FOR STEM SUCCESS

GAMERFIT: A DIGITAL INTERVENTION TO IMPROVE PHYSICAL ACTIVITY AND SLEEP BEHAVIORS IN YOUTH WITH PSYCHIATRIC DIAGNOSES - PROJECT SUMMARY EXERGAMING HAS BEEN SHOWN TO BE AN EFFECTIVE WAY TO INCREASE PHYSICAL ACTIVITY AMONG SEDENTARY YOUTH, INCLUDING THOSE WITH NEURODEVELOPMENTAL AND MENTAL HEALTH DISORDERS. HOWEVER, GAMING TECHNOLOGY IS CONSTANTLY CHANGING, ALONG WITH THE TYPES OF EXERGAMES AVAILABLE. GAMES THAT WERE PREVIOUSLY TESTED IN INTERVENTIONS ARE ROUTINELY DISCONTINUED, AND NEW TECHNOLOGY PLATFORMS AND GAMES ARE EMERGING; THIS EVOLVING LANDSCAPE OF EXERGAMING TECHNOLOGY CRITICALLY IMPACTS EVIDENCE-BASED INTERVENTIONS. UNDERSTANDING HOW COMPONENTS OF AN EXERGAME-BASED PHYSICAL ACTIVITY INTERVENTION AFFECT ENGAGEMENT AMONG YOUTH WITH PSYCHIATRIC DISORDERS MAY LEAD TO CHANGES IN HOW THESE INTERVENTIONS ARE INTEGRATED IN VARIOUS COMMUNITIES. UNFORTUNATELY, HOWEVER, LITTLE IS KNOWN ABOUT HOW TO ASSESS ACCESSIBILITY AND ACCEPTABILITY OF EXISTING AND EMERGING TECHNOLOGY BASED ON INTERSECTIONAL PARTICIPANT CHARACTERISTICS, ESPECIALLY AMONG POPULATIONS TYPICALLY UNDERREPRESENTED IN BEHAVIOR CHANGE STUDIES. THEREFORE, WE AIM TO EXPLORE THE IMPACT OF INTERSECTIONAL CHARACTERISTICS (DISABILITY, RACE/ETHNICITY, GENDER-IDENTITY) ON INTERVENTION ENGAGEMENT WITHIN THE ONGOING GAMERFIT EXERGAMING AND TELEHEALTH COACHING STUDY (PARENT R21 GRANT). THE GAMERFIT STUDY (PARENT R21) WILL RANDOMIZE 60 PARTICIPANTS WITH AT LEAST ONE PD, WITH 30 USING THE GAMERFIT APP WITH WEEKLY TELEHEALTH COACHING SESSIONS AND 30 USING A COMMERCIAL HEALTHY HABITS APP AS A COMPARATOR GROUP. THE GAMERFIT APP WILL PROVIDE ACCESS TO A MENU OF EXERGAMES, PROGRESSIVE PA AND SLEEP PLAN, INTEGRATED SELF-MONITORING, PRE- RECORDED VIDEOS ADDRESSING HEALTHY PA AND SLEEP HABITS, AND MOTIVATIONAL TEXT MESSAGES TO HELP USERS MEET PA AND SLEEP GUIDELINES OVER 12 WEEKS. THIS SUPPLEMENTAL STUDY PROPOSES TO EXPAND THE SCOPE OF THE PARENT GRANT WITH THE FOLLOWING SPECIFIC AIMS: SPECIFIC AIM 1: TO UNDERSTAND HOW PARTICIPANTS’ (N=30 INTERVENTION PARTICIPANTS) RACIAL/ETHNIC AND GENDER IDENTITY INTERSECT WITH PSYCHIATRIC DIAGNOSES TO AFFECT PARTICIPANT PERCEPTIONS OF PHYSICAL ACTIVITY BARRIERS AND BENEFITS, EXERGAMING AND OVERALL INTERVENTION ACCEPTABILITY, AND OVERALL INTERVENTION ENGAGEMENT. SPECIFIC AIM 2: TO EXPLORE HOW RACIAL/ETHNIC AND GENDER IDENTITY INTERSECT WITH PSYCHIATRIC DIAGNOSES TO AFFECT PARTICIPANT PERCEPTIONS OF HOW SPECIFIC EXERGAME COMPONENTS INFLUENCE THEIR ENGAGEMENT OUTCOMES (E.G., ENJOYMENT, ACCEPTABILITY, ACCESSIBILITY, MOTIVATION TO CONTINUE PLAY). THE COMPLETION OF THIS PROPOSED SUPPLEMENTAL PROJECT WILL BOTH YIELD FINDINGS TO IMPROVE THE EFFECTIVENESS AND REACH OF THE GAMERFIT INTERVENTION, AND ALSO ADVANCE DR. KENNEDY’S TRAINING AND CAREER GOALS TO BECOME AN EXPERT IN INTERSECTIONALITY, DISABILITY HEALTH, AND HEALTH BEHAVIOR INTERVENTION DESIGN AND IMPLEMENTATION.

RUI: THE TRANSLOCATION MECHANISM OF NANOMATERIALS IN PLANTS -NANOMATERIALS, MATERIALS MADE UP OF STRUCTURES RANGING FROM 1-100 NANOMETERS, ARE USED WORLDWIDE IN VARIOUS SECTORS INCLUDING MEDICINE, AGRICULTURE, AND INDUSTRY. THESE MATERIALS ARE HIGHLY REACTIVE IN THE ENVIRONMENT AND INTERACT WITH ELEMENTS AVAILABLE IN SOIL AND WATER, AFFECTING THEIR BIOAVAILABILITY FOR PLANTS AND MICROORGANISMS. THE SMALL SIZE OF METAL-BASED NANOMATERIALS RESULTS IN A HIGH RATE OF THEIR UPTAKE BY LIVING ORGANISMS INCLUDING PLANTS. THE IMPACT OF NANOMATERIALS ON LIVING ORGANISMS AND THEIR TOXICITY LEVEL DEPENDS ON VARIOUS FACTORS INCLUDING THEIR SIZE, CONCENTRATION, AND TYPE, AS WELL AS THE EXPOSED ORGANISM. STUDIES ON THE FATE OF NANOMATERIALS IN THE ENVIRONMENT HAVE REPORTED THE POTENTIAL OF PLANTS TO ACCUMULATE NANOMATERIALS. HOWEVER, THE EXACT MECHANISM OF NANOMATERIALS UPTAKE AND THEIR FATE IN PLANTS IS NOT WELL UNDERSTOOD. NANOMATERIALS ACCUMULATED IN PLANTS CAN ENTER THE HUMAN BODY THROUGH DIRECT CONSUMPTION OF PLANTS OR THROUGH THE FOOD CHAIN. THEREFORE, IT IS IMPORTANT TO UNDERSTAND HOW THEY INTERACT WITH PLANTS TO FURTHER PROTECT PUBLIC HEALTH AND IMPROVE SUSTAINABLE AGRICULTURAL PRACTICES. THIS RESEARCH PROJECT INVESTIGATES THE FATE OF THE COMMONLY USED METAL-BASED NANOMATERIAL, SILVER NANOPARTICLES, IN PLANTS AND THEIR INTERACTION WITH ESSENTIAL PLANT NUTRIENTS SUCH AS POTASSIUM, MAGNESIUM, AND ZINC. THIS WILL INVOLVE A SERIES OF MOLECULAR, PHYSIOLOGICAL, AND ANALYTICAL STUDIES TO UNDERSTAND THE FORM AND THE SITE OF ACCUMULATION OF SILVER NANOPARTICLES IN PLANTS, IN ADDITION TO THEIR IMPACT ON MEMBRANE TRANSPORTERS. THE PI WILL MENTOR UNDERGRADUATE AND MASTER?S STUDENTS DURING THE STUDY AND PROVIDE EDUCATIONAL AND RESEARCH OPPORTUNITIES FOR UNDERREPRESENTED MINORITIES IN STEM FIELDS INCLUDING WOMEN, FIRST-GENERATION COLLEGE STUDENTS, AND PEOPLE OF COLOR. TO IMPROVE PUBLIC AWARENESS ABOUT NANOMATERIALS AND THEIR FATE IN PLANTS, A THREE-DIMENSIONAL MODEL WILL BE CREATED BASED ON THE RESULTS OF THIS STUDY AND WILL BE DISPLAYED IN A LOCAL SCIENCE MUSEUM. NANOMATERIALS ARE USED WORLDWIDE IN VARIOUS SECTORS INCLUDING MEDICINE, AGRICULTURE, AND INDUSTRY. SILVER NANOPARTICLES ARE A COMMON FORM OF METAL-BASED NANOMATERIALS. THESE MATERIALS CAN BE OXIDIZED IN THE ENVIRONMENT AND BE TRANSFORMED INTO THE IONIC FORM, WHICH IS MORE INTERACTIVE AND TOXIC THAN THE PARTICULATE FORM. SILVER NANOPARTICLES, IN EITHER PARTICULATE OR IONIC FORM, IMPACT PLANT PHYSIOLOGY AND METABOLISM AT VARIOUS LEVELS INCLUDING THE MEMBRANE TRANSPORTERS AND ELECTRICAL POTENTIAL, WHICH SUBSEQUENTLY AFFECTS PLANT WATER ABSORPTION AND NUTRIENT TRANSLOCATION. SILVER NANOPARTICLES ARE NOT NEEDED FOR PLANT GROWTH AND THERE IS NOT A MEMBRANE TRANSPORTER SPECIFICALLY DESIGNATED FOR SILVER NANOPARTICLES TO ENTER CELLS. HOWEVER, SINCE PLANTS CAN TRANSLOCATE AND ACCUMULATE THESE NANOPARTICLES IN THEIR TISSUES, THERE MUST BE A TRANSPORTER THAT ALLOWS THESE MATERIALS TO PASS ACROSS THE MEMBRANE. PLASMA MEMBRANE AQUAPORIN AND POTASSIUM CHANNELS ARE AMONG THE POSSIBLE TRANSPORTERS FOR SILVER NANOPARTICLES. ONCE THESE NANOPARTICLES ARE TAKEN UP BY PLANTS, THEIR PRESENCE IN INTER- AND INTRA- CELLULAR SPACES CHANGES THE ELECTROCHEMICAL POTENTIAL OF CELLS. TO PROVIDE EQUILIBRIUM, THE EXPRESSION OF SEVERAL MEMBRANE TRANSPORTERS INCLUDING PROTON ATPASE, AND CATION AND ANION CHANNELS CAN BE IMPACTED. THIS IN TURN AFFECTS THE MOVEMENT OF ESSENTIAL NUTRIENTS AND WATER ACROSS THE MEMBRANE, TURGOR PRESSURE, AND CYTOSOLIC AND APOPLASTIC PH LEVEL. THESE SERIES OF EVENTS CAN IMPACT THE STRUCTURE OF XYLEM CELLS AND SUBSEQUENTLY BIOACCUMULATION AND TRANSLOCATION OF ESSENTIAL NUTRIENTS AND WATER IN PLANTS. DUE TO THE ROLE OF AQUAPORINS IN THE TRANSLOCATION OF WATER, MAINTAINING TURGOR PRESSURE, AND POTENTIALLY TRANSPORTING SILVER NANOPARTICLES ACROSS THE MEMBRANE, IN THIS STUDY TOMATO (LYCOPERSICON ESCULENTUM) AND MUTANT FOR AQUAPORIN PIP1 WILL BE EXPOSED TO SILVER NANOPARTICLES IN ORDER TO DETERMINE THE MECHANISM OF TRANSLOCATION OF THESE NANOPARTICLES IN PLANTS AND THEIR INTERACTION WITH PLANT ESSENTIAL NUTRIENTS. THIS PROJECT WILL INCLUDE A SERIES OF ANALYTICAL, MOLECULAR, AND MORPHOLOGICAL ANALYSES TO ACHIEVE THESE AIMS, INCLUDING THE CONCENTRATION, FORM, AND SITE OF SILVER NANOPARTICLES ACCUMULATION IN PLANTS, THE EFFECTS OF THEIR EXPOSURE ON MEMBRANE TRANSPORTERS, AND THE IMPACT OF THEIR EXPOSURE ON VASCULAR TISSUES. RESULTS WILL PROVIDE INFORMATION IN UNDERSTANDING THE FATE OF NANOMATERIALS IN PLANTS AND TO EFFICIENTLY USE PLANTS FOR PHYTOREMEDIATION APPROACHES. 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.

BEHAVIORAL AND NEURAL CORRELATES OF ADAPTIVE RISK-TAKING BEHAVIOR IN PRESCHOOL-AGED CHILDREN - PROJECT SUMMARY ALTHOUGH RISK-TAKING IS TRADITIONALLY ASSOCIATED WITH MALADAPTIVE OUTCOMES, ACCUMULATING EVIDENCE SUGGESTS THAT RISK-TAKING FACILITATES IMPLICIT LEARNING WHICH, CONSEQUENTLY, IMPROVES A VARIETY OF SOCIAL BEHAVIORS. DESPITE THESE FINDINGS, THE ADAPTIVE UTILITY OF RISK-TAKING BEHAVIORS DURING EARLY CHILDHOOD IS OFTEN OVERLOOKED, CAUSING MISSED OPPORTUNITIES TO IMPROVE CONCURRENT AND FUTURE DEVELOPMENTAL OUTCOMES. IT IS CRITICAL THAT THE ADAPTIVE ROLE OF RISK-TAKING IS CHARACTERIZED DURING THE PRESCHOOL YEARS, WHEN THE NEURAL CIRCUITRY THAT UNDERLIES BOTH RISK-TAKING BEHAVIOR AND SOCIAL DEVELOPMENT IS RAPIDLY DEVELOPING. THUS, THE SPECIFIC OBJECTIVE OF THIS PROPOSAL IS TO EXAMINE RELATIONS BETWEEN RISK-TAKING TENDENCIES AND ADAPTIVE PHENOTYPES IN PRESCHOOL-AGED CHILDREN (4 AND 5 YEARS OF AGE). THE CENTRAL HYPOTHESIS OF THIS PROPOSAL IS THAT BEHAVIORAL AND NEURAL MARKERS OF RISK-TAKING WILL RELATE TO IMPLICIT LEARNING AND ADAPTIVE SOCIAL BEHAVIORS IN PRESCHOOLERS. THE RATIONALE FOR THIS RESEARCH IS THAT THE IDENTIFICATION OF ADAPTIVE OUTCOMES ASSOCIATED WITH RISK-TAKING BEHAVIORS WILL INFORM CLINICAL INTERVENTIONS AND EDUCATIONAL PRACTICES THAT ENCOURAGE APPROPRIATE AND SYSTEMATIC RISK-TAKING TO BOLSTER LEARNING AND SOCIAL DEVELOPMENT IN YOUNG CHILDREN. THE CENTRAL HYPOTHESIS WILL BE TESTED THROUGH THREE SPECIFIC AIMS: 1) TO DEFINE ASSOCIATIONS BETWEEN RISK-TAKING AND IMPLICIT LEARNING (AIM 1), PRESCHOOL-AGED CHILDREN WILL COMPLETE A COMPUTERIZED RISK-TAKING TASK THAT RELIES ON IMPLICIT LEARNING. THE RATE OF RISK-TAKING BEHAVIOR AT THE BEGINNING OF THE TASK WILL BE COMPARED TO OVERALL TASK PERFORMANCE TO DETERMINE HOW EXPLORATORY RISK-TAKING AFFECTS LEARNING; 2) TO DELINEATE RELATIONS BETWEEN RISK-TAKING AND SOCIAL BEHAVIOR (AIM 2), OUTCOMES FROM THE RISK-TAKING TASK WILL BE CORRELATED WITH CAREGIVER- AND TEACHER-REPORT OF CHILDREN’S SOCIAL BEHAVIORS OBTAINED THROUGH GOLD-STANDARD ASSESSMENTS AS WELL AS A SECONDARY RISK-TAKING TASK DESIGNED TO DIRECTLY ASSESS CHILD ENGAGEMENT IN SOCIAL RISK; AND 3) TO IDENTIFY NEURAL MECHANISMS UNDERLYING RISK-TAKING TENDENCIES IN PRESCHOOL-AGED CHILDREN (EXPLORATORY AIM 3), A SEPARATE SAMPLE OF CHILDREN WILL COMPLETE THE RISK-TAKING TASK WHILE BRAIN ACTIVITY IS SIMULTANEOUSLY RECORDED VIA ELECTROENCEPHALOGRAPHY (EEG). OUTCOMES FROM THE EEG RECORDING (E.G., EVENT-RELATED POTENTIALS AND SPECTRAL POWER) WILL BE CORRELATED WITH PERFORMANCE ON THE RISK-TAKING MEASURES. THIS PROPOSAL IS INNOVATIVE BECAUSE IT IS EXPECTED TO PROVIDE STRONG SCIENTIFIC JUSTIFICATION FOR THE CONCEPTUALIZATION OF RISK-TAKING AS A DYNAMIC CONSTRUCT WITH ADAPTIVE OUTCOMES INCLUDING LEARNING AND SOCIAL BEHAVIORS. THIS HYPOTHESIS CONTRASTS THE TRADITIONAL DEFICIT APPROACH TO RISK-TAKING DURING EARLY CHILDHOOD WHEN RISK-TAKING IS PRESUMED DANGEROUS AND OFTEN DISCOURAGED. THIS WORK IS SIGNIFICANT BECAUSE EVIDENCE OF RISK-TAKING AS AN ADAPTIVE BEHAVIOR MAY REFORM CLINICAL AND EDUCATIONAL PRACTICES THAT DISCOURAGE RISK-TAKING BEHAVIORS. FURTHERMORE, THE USE OF EEG IS EXPECTED TO ELUCIDATE NEW, MECHANISTIC INSIGHTS INTO NEURAL CORRELATES OF RISK-TAKING IN PRESCHOOLERS AND, CONSEQUENTLY, INFORM CLINICAL TARGETS IN POPULATIONS THAT EXHIBIT MALADAPTIVE RISK-TAKING BEHAVIORS. THIS PROPOSAL ALSO OFFERS UNIQUE TRAINING OPPORTUNITIES TO UNDERGRADUATES AND WILL BUILD RESEARCH INFRASTRUCTURE AT THE PI’S HOME INSTITUTION.

RESET: REGULATION OF EMOTION, SLEEP EXTENSION, AND MTBI - PROJECT SUMMARY GIVEN THAT BOTH SLEEP DISRUPTION AND MILD TRAUMATIC BRAIN INJURY (MTB) CAN IMPACT EXECUTIVE CONTROL OF EMOTION REGULATION, IT IS POSSIBLE THAT IMPROVING SLEEP QUALITY MAY REDUCE THE EMOTION DYSREGULATION ASSOCIATED WITH MTBI; THEREFORE, SLEEP EXTENSION MAY BE AN ACCESSIBLE AND EFFECTIVE WAY TO IMPROVE SOME OF THE COMMON SYMPTOMS ASSOCIATED WITH MTBIS. AS THE PREVALENCE OF MTBI IS EXTREMELY HIGH, IT IS CRITICAL TO DETERMINE WAYS TO MITIGATE IMPAIRMENTS. REDUCING EMOTION DYSREGULATION COULD ALLEVIATE SYMPTOMS OF ANXIETY, DEPRESSION, AND OTHER MENTAL HEALTH CONCERNS IN INDIVIDUALS WITH MTBI. NAPPING HAS BEEN SHOWN TO IMPACT EMOTIONAL MEMORY CONSOLIDATION AND EMOTIONAL REACTIVITY, AND TO INCREASE FRUSTRATION TOLERANCE IN ADULTS. HOWEVER, NO RESEARCH HAS EXAMINED THE ROLE OF NAPPING IN EMOTION REGULATION OF MTBI INDIVIDUALS. TO ADDRESS THIS CRITICAL GAP, WE AIM TO EXAMINE THE PRELIMINARY EFFICACY OF A MID-DAY NAP TO IMPROVE EMOTION REGULATION IN INDIVIDUALS WHO HAVE RECENTLY SUSTAINED A MTBI, AND TO EXAMINE WHETHER A MID-DAY NAP ALTERS TOP-DOWN NEURAL CONTROL OF EMOTION REGULATION IN THIS POPULATION. TO DO THIS, INDIVIDUALS WHO HAVE HAD A MTBI WITHIN THE LAST MONTH WILL PARTICIPATE IN AN EMOTION REGULATION TASK AFTER BOTH A NAP AND A NO-NAP CONDITION, COUNTERBALANCED. WE WILL MEASURE BOTH BEHAVIORAL (EYE TRACKING) AND SELF-REPORT RESPONSES TO EMOTIONAL STIMULI (E.G., THEIR ABILITY TO REAPPRAISE AND REDUCE THEIR NEGATIVE EMOTIONAL RESPONSE WHEN ASKED TO DO SO), AS WELL AS TOP-DOWN CONTROL, AS MEASURED BY PUPIL DILATION THROUGH PUPILLOMETRY AND THE LATE POSITIVE POTENTIAL (LPP) THROUGH ERP. THE SIGNIFICANCE OF THIS WORK IS EXAMINING THE RELATIONSHIP BETWEEN EMOTION REGULATION, SLEEP IN THE FORM OF A NAP, AND MTBIS, AS WELL AS THE ABILITY TO ASSESS THE POSSIBLE THERAPEUTIC FUNCTION OF A DAYTIME NAP TO REDUCE EMOTION DYSREGULATION SYMPTOMS. THE INNOVATION LIES IN THE ABOVE SIGNIFICANCE AND AIMS TO ADDRESS THE CRITICAL GAP IN THE LITERATURE AND ITS ABILITY TO SHIFT THE CURRENT CLINICAL PRACTICE FOR MTBI, AS WELL AS THE COMBINED EXPERIMENTAL DESIGN (EYE TRACKING, POLYSOMNOGRAPHY) OF THE PROPOSAL. THE LONG-TERM GOAL OF THIS RESEARCH IS TO DETERMINE HOW SLEEP-BASED INTERVENTIONS MAY IMPROVE COGNITIVE AND EMOTIONAL OUTCOMES FOLLOWING MTBI, WHICH COULD BE A COST-EFFECTIVE AND ACCESSIBLE ADDITION TO A MTBI REHABILITATION PROGRAM.

SCIENTIFIC STUDIES FROM A NETWORK OF SUSTAINABLE, ROBOTIC OBSERVATORIES ACROSS THE ANTARCTIC ICE-SHELF: A NEW APPROACH TO POLAR RESEARCH

A CRISPR-BASED TOOLKIT FOR INVESTIGATING HAIR CELL TRANSCRIPTION FACTORS IN INNER EAR ORGANOIDS - PROJECT SUMMARY/ABSTRACT HAIR CELLS (HCS) ARE THE SPECIALIZED SENSORY CELLS OF THE INNER EAR THAT PLAY A CRUCIAL ROLE IN TRANSMITTING ENVIRONMENTAL INFORMATION, SUCH AS SOUND AND MOTION, TO THE BRAIN. IN ADULT MAMMALS, HCS CANNOT REGENERATE NATURALLY. THEREFORE, A LARGE EFFORT HAS BEEN MADE TO UNDERSTAND THE NORMAL DEVELOPMENT OF AUDITORY AND VESTIBULAR HCS, SO THAT EFFECTIVE REGENERATIVE THERAPIES CAN BE ESTABLISHED. TECHNOLOGICAL ADVANCEMENTS IN STUDYING TRANSCRIPTIONAL CONTROL HAVE PROVIDED VALUABLE INSIGHTS INTO THE ROLES OF DIFFERENT TRANSCRIPTION FACTORS (TFS) SUCH AS ATOH1, POU4F3, GFI1, INSM1, TBX2, AND IKZF2 IN THE DEVELOPMENT OF HCS. HOWEVER, THE APPLICATION OF CERTAIN TOOLS, SUCH AS CRISPR-MEDIATED GENE ACTIVATION AND INHIBITION, FOR STUDYING HC DEVELOPMENT HAS BEEN LIMITED BY THE COMPLICATED USE OF ANIMAL MODELS. RECENTLY, A HIGHLY SCALABLE PROTOCOL WAS DEVELOPED TO GUIDE MOUSE EMBRYONIC STEM CELLS (MESCS) TOWARDS INNER EAR SENSORY CELLS IN VITRO. OVER A SPAN OF 2-3 WEEKS, THESE INNER EAR ORGANOIDS PRODUCE SENSORY EPITHELIA-LIKE STRUCTURES COMPLETE WITH MECHANOSENSITIVE HCS AND UNDERLYING SUPPORTING CELLS. THE DEVELOPMENT OF THIS INNER EAR ORGANOID MODEL FACILITATES THE PROGRESS OF CELL-BASED ASSAYS FOR STUDYING HC-SPECIFIC DEVELOPMENT AND TESTING POTENTIAL TREATMENTS FOR SENSORY CELL LOSS. IN THIS PROPOSAL, I AIM TO UTILIZE THE INNER EAR ORGANOID MODEL TO INVESTIGATE THE TRANSCRIPTIONAL CONTROL OF HC DEVELOPMENT IN VITRO. TO ACHIEVE THIS, I PLAN TO: I. DEFINE THE TFS INVOLVED IN IN VITRO INNER EAR ORGANOID HC DEVELOPMENT COMPARED TO IN VIVO HC DEVELOPMENT. II. GENERATE A VERSATILE TOOLKIT OF MESC LINES DESIGNED FOR INDUCIBLE AND REVERSIBLE CRISPR-MEDIATED GENE ACTIVATION AND INHIBITION. III. UTILIZE THIS TOOLKIT TO SYSTEMATICALLY INVESTIGATE THE ROLES OF CANDIDATE TFS IN ORGANOID HCS THROUGH CRISPR-MEDIATED KNOCKDOWN AND ACTIVATION, FOLLOWED BY MULTI-OMIC ANALYSES. SUCCESSFUL COMPLETION OF THIS PROJECT WILL NOT ONLY UNCOVER ADDITIONAL TFS ESSENTIAL FOR HC DEVELOPMENT BUT WILL ALSO PROVIDE A VALUABLE RESOURCE FOR FELLOW INNER EAR RESEARCHERS SEEKING TO MANIPULATE THE EXPRESSION OF GENES OF INTEREST WITHIN INNER EAR ORGANOID CELL TYPES.

DEVELOPMENT OF RESEARCH TO INFORM THE DESIGN AND IMPROVEMENT OF MATHEMATICS EDUCATION FOR TEACHERS

COLLABORATIVE RESEARCH: SYNOPTIC GEOSPACE SYSTEMS ANALYSIS UTILIZING INSTRUMENTATION FROM SOUTH POLE AND MCMURDO STATIONS

ASSESSMENT OF 1D NONLINEAR SITE RESPONSE UNCERTAINTY AT A LARGE NUMBER OF VERTICAL SEISMOMETER ARRAYS

G18AP00016 MERRIMACK (EHP)

PROJECT TITLE: BASIN EFFECTS IN THE CENTRAL AND EASTERN UNITED STATES: COLLABORATIVE RESEARCH WITH TUFTS UNIVERSITY AND MERRIMACK COLLEGEPROJECT PERIOD: 87 1 2023 THROUGH 7 31 2024PLAIN LANGUAGE DESCRIPTION: THE PURPOSE OF THIS AWARD IS TO IMPROVE BASIN TERMS IN GROUND MOTION MODELS USING GEOSPATIAL, GEOLOGICAL, GEOMORPHIC, AND GEOTECHNICAL DATA TO CHARACTERIZE SEDIMENTARY BASINS IN THE CENTRAL AND EASTERN UNITED STATES.ACTIVITIES TO BE PERFORMED: GROUND MOTION DATA RECORDED IN THE CENTRAL AND EASTERN UNITED STATES SINCE 2011 WILL BE COMPILED AND PROCESSED TO ENHANCE THE EXISTING NGA-EAST (NEXT GENERATION ATTENUATION RELATIONSHIPS FOR CENTRAL EASTERN NORTH-AMERICA PROJECT) GROUND MOTION FLATFILE. GEOLOGIC, TOPOGRAPHIC, GEOMORPHIC, AND GEOTECHNICAL DATA TO CHARACTERIZE SEDIMENTARY BASINS AND SITES WILL BE COMPILED IN THE CENTRAL AND EASTERN UNITED STATES. USING MIXED-EFFECTS REGRESSION, WE WILL DETERMINE WHICH BASIN CHARACTERISTICS BEST REDUCE UNCERTAINTY IN EXISTING NGA-EAST GROUND MOTION MODELS.DELIVERABLES AND EXPECTED OUTCOMES: AN EXPANDED GROUND MOTION NGA-EAST FLATFILE WITH ENHANCED BASIN TERMS AND ADDITIONAL SITE METADATA WILL BE PRODUCED AS PART OF THE PROJECT. REGRESSION MODELS WILL BE DEVELOPED FOR ADJUSTMENT FACTORS FOR SITE EFFECTS IN DIFFERENT BASINS AND GEOLOGY GROUPS. A FINAL TECHNICAL REPORT, AN ABSTRACT AND PRESENTATION AT THE 2024 SEISMOLOGICAL SOCIETY OF AMERICA (SSA) ANNUAL MEETING, AND A PEER-REVIEWED JOURNAL PAPER WILL BE PRODUCED TO SUMMARIZE THE WORK AND PRESENT THE RESULTS OF THE BASIN TERM EVALUATION.INTENDED BENEFICIARIES: IMPROVED BASIN TERMS IN GROUND MOTION MODELS WILL REDUCE THE GROUND MOTION UNCERTAINTY IN PROBABILISTIC SEISMIC HAZARD ANALYSES, AND ULTIMATELY BENEFIT ALL THOSE WHO USE REGIONAL AND LOCAL SEISMIC HAZARD PRODUCTS INCLUDING ENGINEERS, PLANNERS, AND LOSS ESTIMATORS.SUBRECIPIENT ACTIVITIES: NIA

PROJECT TITLE: HVSR SITE TERMS FOR NONERGODIC GROUND MOTION MODELS: COLLABORATIVE RESEARCH WITH TUFTS UNIVERSITY AND MERRIMACK COLLEGEPROJECT PERIOD: 8 1 2023 THROUGH 7 31 2024PLAIN LANGUAGE DESCRIPTION: THE PURPOSE OF THIS AWARD IS TO IMPROVE SITE TERMS IN GROUND MOTION MODELS USING A COMBINATION OF FREQUENCY, SHAPE, AND AMPLITUDE STATISTICS DERIVED FROM THE HORIZONTAL-TO-VERTICAL SPECTRAL RATIO OF OBSERVED GROUND MOTION DATA.ACTIVITIES TO BE PERFORMED: GROUND MOTION DATA ASSOCIATED WITH THE NGA-SUB (NEXT-GENERATION ATTENUATION FOR SUBDUCTION ZONE REGIONS PROJECT) FLATFILE WILL BE COMPILED. SINGLE-STATION HORIZONTAL-TO-VERTICAL SPECTRAL RATIOS WILL BE CALCULATED FOR PRE-EVENT NOISE, WEAK EARTHQUAKE MOTIONS, AND STRONG EARTHQUAKE MOTIONS AT EACH STATION. A DATABASE OF HORIZONTAL TO VERTICAL SPECTRAL RATIO SHAPE PARAMETERS, INCLUDING NUMBER OF PEAKS, PEAK FREQUENCY, PEAK AMPLITUDE, PROMINENCE, HALF-POWER BANDWIDTH, AND INTEREVENT VARIABILITY OF SIGNIFICANT PEAKS WILL BE ASSEMBLED. USING LINEAR MIXED-EFFECTS REGRESSION AND EXISTING GROUND MOTION MODELS, SITE TERMS WILL BE CALCULATED AT EACH OF THE NGA-SUB STATIONS. THE RESULTS WILL BE USED TO DERIVE NEW SITE EFFECTS MODELS USING HORIZONTAL-TO-VERTICAL SPECTRAL RATIO PARAMETERS. THE NEW SITE-EFFECTS MODELS WILL BE EVALUATED AND COMPARED TO TERMS IN EXISTING MODELS FOR SITE EFFECTS.DELIVERABLES AND EXPECTED OUTCOMES: A DATABASE OF HORIZONTAL TO VERTICAL SPECTRAL RATIO SHAPE PARAMETERS, INCLUDING NUMBER OF PEAKS, PEAK FREQUENCY, PEAK AMPLITUDE, PROMINENCE, HALF-POWER BANDWIDTH, AND INTEREVENT VARIABILITY OF SIGNIFICANT PEAKS WILL BE ASSEMBLED. USING THE COMPILED DATABASE, NEW MODELS FOR SITE EFFECTS WILL BE DEVELOPED IN TERMS OF HORIZONTAL-TO-VERTICAL SPECTRAL RATIO PARAMETERS. A FINAL TECHNICAL REPORT, AN ABSTRACT AND PRESENTATION AT THE 2024 SEISMOLOGICAL SOCIETY OF AMERICA (SSA) ANNUAL MEETING, AND A PEER-REVIEWED JOURNAL PAPER WILL BE PRODUCED TO SUMMARIZE THE WORK AND PRESENT THE RESULTS OF THE SITE TERM EVALUATION.INTENDED BENEFICIARIES: IMPROVED SITE TERMS IN GROUND MOTION MODELS WILL REDUCE THE GROUND MOTION UNCERTAINTY IN PROBABILISTIC SEISMIC HAZARD ANALYSES, AND ULTIMATELY BENEFIT ALL THOSE WHO USE REGIONAL AND LOCAL SEISMIC HAZARD PRODUCTS INCLUDING ENGINEERS, PLANNERS, AND LOSS ESTIMATORS.SUBRECIPIENT ACTIVITIES: NIA

PROJECT TITLE: USING DID YOU FEEL IT? DATA TO MAP SPATIALLY VARIABLE SITE AMPLIFICATION IN GLACIATED TERRAIN, INCLUDING DATA FROM THE 2024 NEW JERSEY EARTHQUAKE: COLLABORATIVE RESEARCH WITH TUFTS UNIVERSITY AND MERRIMACK COLLEGEPROJECT PERIOD: 8 1 2025 THROUGH 7 31 2026AWARD PURPOSE: MACROSEISMIC INTENSITY RECORDINGS ARE AN UNDERUTILIZED SOURCE OF HIGH RESOLUTION, SITE-SPECIFIC DATA FOR SITE RESPONSE ASSESSMENT. INTENSITY PREDICTION EQUATIONS, WHICH PREDICT MODIFIED MERCALLI INTENSITY (MMI) FOR EARTHQUAKES, ARE AN IMPORTANT TOOL FOR REAL-TIME SEISMIC HAZARD ASSESSMENT AND INTERPRETATIONS OF SHAKING FROM HISTORIC AND RECENT EARTHQUAKES. THIS WORK WILL UTILIZE DID YOU FEEL IT? (DYFI) DATASETS IN THE CENTRAL AND EASTERN UNITED STATES (CEUS) TO VERIFY RECENTLY DEVELOPED SITE AND BASIN TERMS FOR THE REGION AND IMPROVE INTENSITY PREDICTION EQUATIONS. THE RECIPIENT WILL PAIR GEOSPATIAL DATA (WHICH PROVIDE BROAD SPATIAL COVERAGE OF SITE CHARACTERISTICS) WITH DYFI DATA (WHICH PROVIDE BROAD SPATIAL COVERAGE OF MACROSEISMIC INTENSITIES) TO DEVELOP SITE TERMS FOR INTENSITY PREDICTION EQUATIONS. FURTHER, WE HYPOTHESIZE THAT SPATIALLY RICH DYFI DATA CAN BE USED TO BETTER UNDERSTAND SITE AND BASIN EFFECTS DURING EARTHQUAKES, BECAUSE MACROSEISMIC INTENSITY DATA IS AVAILABLEAT SUCH A STRONGER SPATIAL RESOLUTION THAN TRADITIONAL GROUND-MOTION RECORDINGS.ACTIVITIES TO BE PERFORMED: FIRST, WE WILL COLLECT AND COMPILE ALL DYFI RESPONSES FROM 1999 TO 2024 IN THE PREVIOUSLY GLACIATED TERRAIN OF THE CEUS TO PRODUCE A MACROSEISMIC INTENSITY DATABASE. VARIABLES OF INTEREST INCLUDE THE REPORTED MODIFIED MERCALLI INTENSITY (MMI), HYPOCENTRAL DISTANCE, EPICENTRAL DISTANCE, NUMBER OF DYFI RESPONSES, POPULATION, EARTHQUAKE MAGNITUDE, EARTHQUAKE DATE, AS WELL AS SITE AND BASIN TERMS. SECOND, WE WILL USE THE ATKINSON ET AL. (2014) INTENSITY PREDICTION EQUATION TO PREDICT MMI FOR EACH 1 KM GRID SQUARE USING THE 2024 M 4.8 TEWKSBURY, NJ, EARTHQUAKE, AND COMPUTE RESIDUALS BETWEEN THE OBSERVED AND PREDICTED INTENSITIES. THESE EVENT-SPECIFIC RESIDUALS WILL BE EXAMINED TO SEARCH FOR HIGH-RESOLUTION SPATIAL TRENDS WITH THE PREVIOUSLY PROPOSED SITE TERMS. THE THIRD TASK WILL BE TO EXPAND THIS RESIDUAL ANALYSIS TO INCLUDE ALL DYFI DATA IN OUR MACROSEISMIC DATABASE, INCLUDING ANY REPORTS IN THE GLACIATED TERRAIN FROM 1999 TO 2024 IN THE GLACIATED TERRAIN. THE RECIPIENT WILL PERFORM LINEAR MIXED EFFECTS REGRESSION TO OBTAIN INTENSITY-BASED SITE-TO-SITE RESIDUAL TERMS.FINALLY, USING THE FULL MACROSEISMIC DATABASE AND CALCULATED RESIDUALS FROM THE RELEVANT EVENTS, THE RECIPIENT WILL USE RESIDUAL ANALYSIS TO EXAMINE HIGH-RESOLUTION, REPEATED, SITE-SPECIFIC EFFECTS. WE WILL COMPARE THESEINTENSITY-BASED SITE-TO-SITE RESIDUAL TERMS WITH OUR PROPOSED SPATIALLY CONTINUOUS SITE AND BASIN TERMSCREATED FROM SEDIMENT THICKNESS, WAVELET COEFFICIENT, AND SURFICIAL ROUGHNESS.DELIVERABLES AND EXPECTED OUTCOMES: THE DELIVERABLES OF THIS RESEARCH WILL BE: (A) A MACROSEISMIC DATABASE INCLUDING GEOSPATIAL AND GEOLOGY-BASED SITE TERMS, (B) RESIDUAL ANALYSIS FOR THE MACROSEISMIC DATABASE USING THE ATKINSON ET AL. (2014) INTENSITY PREDICTION EQUATION, AND (C) A NEW SITE TERM FOR USEIN INTENSITY PREDICTION EQUATIONS.INTENDED BENEFICIARIES: THIS PROJECT IS FOCUSED ON DID YOU FEEL IT? DATA IN CENTRAL AND EASTERN UNITED STATES, WITH A FOCUS ON PREVIOUSLY GLACIATED TERRAIN. THIS PROJECT WILL THEREFORE BENEFIT PUBLIC AGENCIES, STATE AGENCIES, FEDERAL AGENCIES, AND STAKEHOLDERS THAT ARE INTERESTED IN THE USGS GROUND MOTION PRODUCTS FOR THIS REGION. IN ADDITION, THIS PROJECT WILL IMPACT THE PROFESSIONAL DEVELOPMENT OF ONE GRADUATE STUDENT RESEARCHER AND ONE UNDERGRADUATE STUDENT RESEARCHER, AS WELL AS STUDENTS AT BOTH TUFTS UNIVERSITY AND MERRIMACK COLLEGE. WE ALSO INTEND TO WRITE AN ACCESSIBLE AND AVAILABLE ARTICLE OUTLINING OUR WORK WITH DYFI DATA TO ENCOURAGE PUBLIC EDUCATION AND ENGAGEMENT.SUBRECIPIENT ACTIVITIES: N A

PROJECT TITLE: GEOSPATIAL AND GEOLOGIC SITE TERMS FOR NONERGODIC GROUND MOTION MODELS FOR CALIFORNIA AND UTAH:COLLABORATIVE RESEARCH WITH TUFTS UNIVERSITY AND MERRIMACK COLLEGEPROJECT PERIOD: 8 1 2025 THROUGH 7 31 2026AWARD PURPOSE: EARTHQUAKE GROUND-MOTION MODELS (GMMS) ARE A CRITICAL COMPONENT OF SEISMIC HAZARD ASSESSMENT. IN ORDER TO ACHIEVE MORE ACCURATE MODELING OF SITE EFFECTS IN GMMS THAT ARE BOTH INFORMATIVE OF GEOLOGIC CONDITIONS AND SPATIALLY CONTINUOUS (I.E., ABLE TO BE MEASURED AT ANY LOCATION WITHIN THE MODELED AREA), WE PROPOSE A PARADIGM SHIFT FOR GROUND-MOTION MODELING. INSTEAD OF FOCUSING THE DEVELOPMENT OF GMM SITE TERMS ON SITE-SPECIFIC VELOCITY PROFILES THAT ARE NOT UNIVERSALLY AVAILABLE, THE RECIPIENT HYPOTHESIZE THAT INCORPORATING BROADLY-AVAILABLE GEOSPATIAL AND GEOLOGICAL DATA BEFORE SITE-SPECIFIC SEISMIC VELOCITIES WILL LEAD TO IMPROVEMENTS IN SITE-TO-SITE RESIDUALS IN GMMS. THE OBJECTIVE OF THIS STUDY IS TO DEVELOP A SPATIALLY-CONTINUOUS SITE EFFECTS MODEL FOR GMMS FOR CALIFORNIA AND UTAH THAT CAN BE UPDATED WITH SITE-SPECIFIC DATA, ALLOWING FOR IMPROVED AND INCLUSIVE RISK ESTIMATION. THE SPATIALLY CONTINUOUS DATA WILL BE DERIVED FROM DIGITAL ELEVATION MODELS AND SURFICIAL GEOLOGY MAPS FOR EACH STATE. THE FUNDAMENTAL PARAMETERS OF THE GMM SITE TERMS WILL INVOLVE GEOSPATIAL PARAMETERS AND REGIONAL GEOLOGY, AND OUR FRAMEWORK WILL ALLOW FOR THE GMM TO BE UPDATED WITH SITE-SPECIFIC GEOTECHNICAL DATA WHERE IT IS AVAILABLE.ACTIVITIES TO BE PERFORMED: THE ACTIVITIES TO BE PERFORMED INCLUDE: (1) DEVELOP A SPATIALLY-CONTINUOUS NONERGODIC SITE TERM FOR GMMS IN CALIFORNIA USING GEOSPATIAL VARIABLES AND STATE-LEVEL SURFICIAL GEOLOGY (2) DEVELOP A SPATIALLY-CONTINUOUS NONERGODIC SITE TERM FOR GMMS IN UTAH USING GEOSPATIAL VARIABLES AND STATE-LEVEL SURFICIAL GEOLOGY AND (3) COMPARE THE RESULTS OF THESE MODELS WITH OTHER PUBLISHED ERGODIC AND NONERGODIC GMMS IN TERMS OF SITE-TO-SITE VARIABILITY REDUCTION, AND PROVIDE RECOMMENDATIONS ON ADDING SITE-SPECIFIC GEOTECHNICAL SITE CHARACTERIZATION FOR FURTHER UNCERTAINTY REDUCTION.DELIVERABLES AND EXPECTED OUTCOMES: THE DELIVERABLES OF THIS RESEARCH WILL BE: (A) A GEOSPATIAL AND GEOLOGIC SITE TERMS DATASET FOR CALIFORNIA AND UTAH (B) MAP-BASED GEOSPATIAL AND GEOLOGY-BASED SITE TERMS FOR USE WITH AN ERGODIC BASE GMM FOR BOTH CALIFORNIA AND UTAH, AND (C) AN IMPLEMENTATION MODEL FOR USING ALL THREE LEVELS OF SITE TERMS (GEOSPATIAL, GEOLOGIC, AND GEOTECHNICAL) WITH EXISTING GROUND MOTION MODELS. THE SITE TERMS WILL BE PROVIDED IN GEOGRAPHIC INFORMATION SYSTEM (GIS) RASTER FORMAT FOR EASY ACCESS THROUGH AN ONLINE REPOSITORY.INTENDED BENEFICIARY(IES): THIS PROJECT IS FOCUSED ON CALIFORNIA AND UTAH. THE DEVELOPMENT OF GROUND MOTION MODELS USING BROADLY-AVAILABLE GEOSPATIAL AND GEOLOGICAL DATA WILL REDUCE THE UNCERTAINTY IN SEISMIC HAZARD ESTIMATIONS FOR EACH STATE. THIS PROJECT WILL THEREFORE BENEFIT PUBLIC AGENCIES, STATE AGENCIES, FEDERAL AGENCIES, AND STAKEHOLDERS THAT PERFORM SEISMIC DESIGN IN THESE REGIONS. MOREOVER, THE GROUND-MOTION MODELING FRAMEWORK THAT WE DEVELOP COULD BE APPLIED TO BROADER AREAS IN THE FUTURE. THE LONG-TERM GOAL OF THIS RESEARCH IS TO IMPROVE THE SITE TERM MODELS FOR USE IN NONERGODIC GMMS, WHICH WILL PROVIDE HIGHER RESOLUTION AND MORE ACCURATE ESTIMATES OF GROUND MOTIONS FOR SEISMIC HAZARD ASSESSMENT AND USE IN REAL TIME GROUND MOTION PRODUCTS. IN ADDITION, THIS PROJECT WILL IMPACT THE PROFESSIONAL DEVELOPMENT OF ONE GRADUATE STUDENT RESEARCHER AND ONE UNDERGRADUATE STUDENT RESEARCHER, AS WELL AS STUDENTS AT BOTH TUFTS UNIVERSITY AND MERRIMACK COLLEGE.SUBRECIPIENT ACTIVITIES: N A

COASTAL PLAIN AMPLIFICATION AND HAZARD MODEL FOR THE NATIONAL SEISMIC HAZARD MODEL: COLLABORATIVE RESEARCH WITH UNIVERSITY OF MEMPHIS, NCSU, & MERRIMACK COLLEGE, DATED 5/29/2021