Miami University

MIAMI UNIVERSITY HIGHER EDUCATION EMERGENCY RELIEF FUND - INSTITUTIONAL PORTION

MIAMI UNIVERSITY CARES ACT FUNDING CERTIFICATION AND AGREEMENT

EPR SPECTROSCOPIC STUDIES OF MEMBRANE PROTEINS

TRIAGE MECHANISMS FOR DIRECTING PROTEIN REFOLDING AND DEGRADATION

MIAMI UNIVERSITY MENTAL HEALTH SERVICE PROFESSIONAL WORKFORCE DEVELOPMENT PROJECT

THE ROLE OF FGF RECEPTORS IN LENS DEVELOPMENT

GRANT

DISSIPATIVE ASSEMBLY OF CARBOXYLIC ACID ANHYDRIDES FOR NONEQUILIBRIUM SYSTEMS CHEMISTRY

ANALYSIS OF A NOVEL SENSORY MECHANISM IN ROOT PHOTOTROPISM

SUSTAINED REGULATION OF HYPOTHALAMUS-PITUITARY-OVARY HORMONES WITH TISSUE-ENGINEERED OVARIAN CONSTRUCTS AS A TREATMENT FOR OSTEOPOROSIS IN FEMALES - SUSTAINED REGULATION OF HYPOTHALAMUS-PITUITARY-OVARY HORMONES WITH TISSUE- ENGINEERED OVARIAN CONSTRUCTS AS A TREATMENT FOR OSTEOPOROSIS IN FEMALES PROJECT SUMMARY/ABSTRACT FEMALES ARE DISPROPORTIONATELY AFFECTED BY OSTEOPOROSIS AND OSTEOPOROTIC FRACTURE. IN THE U.S., APPROXIMATELY 40 MILLION WOMEN HAVE OR ARE AT RISK OF DEVELOPING OSTEOPOROSIS AND THE MAJORITY (~ 60%) OF THE 2 MILLION OSTEOPOROTIC BONE FRACTURES (DIRECT COSTS > $20 BILLION PER YEAR) OCCUR IN WOMEN. WOMEN HAVE A 1-IN-2 LIFETIME CHANCE OF HAVING AN OSTEOPOROTIC FRACTURE AND A 4-FOLD HIGHER RATE OF OSTEOPOROSIS THAN MEN. A KEY UNDERLYING CAUSE IS OVARIAN FAILURE DUE TO MENOPAUSE OR OTHER CONDITIONS THAT LEAD TO LOSS OF OVARIAN HORMONES WITH CONCOMITANT DISRUPTION OF THE HYPOTHALAMUS-OVARY-PITUITARY (HPO) AXIS. UNTIL 2002, TRADITIONAL PHARMACOLOGICAL HORMONE THERAPY (PHT) WAS WIDELY USED DUE TO ITS PERCEIVED ABILITY TO REDUCE RISK OF OSTEOPOROSIS AND, IMPORTANTLY, OSTEOPOROTIC FRACTURE. THE WOMEN’S HEALTH INITIATIVE (WHI) VERIFIED THIS LONG-HELD BELIEF, DEMONSTRATING THAT PHT REDUCED INCIDENCE OF OSTEOPOROTIC FRACTURE. HOWEVER, THE WHI ALSO INDICATED THAT THE RISKS OF HORMONE THERAPY, SUCH AS CARDIOVASCULAR DISEASE AND CERTAIN TYPES OF CANCER, OUTWEIGHED THE BENEFITS OF REDUCED LEVELS OF OSTEOPOROSIS. FOLLOW-ON STUDIES INDICATE THAT RISKS MAY BE HIGHER IN WOMEN OLDER THAN 60 YEARS OF AGE AND/OR MORE THAN 10 YEARS POST-MENOPAUSE, SUGGESTING THAT HORMONE THERAPY MAY STILL BE EFFECTIVE IF GIVEN AT LOWER, SAFER DOSES AND VIA SUITABLE DELIVERY PLATFORMS. WE PROPOSE BIOMIMETIC, OVARIAN CELL CONSTRUCTS AS A TISSUE ENGINEERING APPROACH TO HORMONE DELIVERY (CELLULAR HORMONE THERAPY; CHT) IN THE TREATMENT OF OSTEOPOROSIS. THE HYPOTHESIS GUIDING THIS RESEARCH IS THAT CHT CAN ACHIEVE BETTER BONE HEALTH AND SAFETY OUTCOMES THAN PHARMACOLOGICAL AGENTS, SUCH AS PHT OR THE BISPHOSPHONATES, IN OVARIAN FAILURE BECAUSE IT MIMICS NATIVE OVARIAN STRUCTURE AND FUNCTION. OUR CHT APPROACH USES A SPATIAL ARRANGEMENT OF TWO KEY OVARIAN CELL TYPES (GRANULOSA AND THECA CELLS) THAT MIMICS NATIVE OVARIAN FOLLICLE STRUCTURE WHILE AVOIDING PITFALLS OF WHOLE OVARIAN TISSUE ENCAPSULATION SUCH AS OOCYTE (EGG) EXPULSION AND LOSS OF FUNCTION WITH TIME. OUR SYSTEM HAS ACHIEVED SUSTAINED AND PHYSIOLOGICALLY- RELEVANT LEVELS OF OVARIAN HORMONE SECRETION. WE HAVE DEMONSTRATED THAT THE ENCAPSULATED OVARIAN CELLS PARTICIPATE IN THE HPO AXIS, AS EVIDENCED BY REGULATION OF FOLLICLE STIMULATING HORMONE (FSH) AND LUTEINIZING HORMONE (LH) LEVELS FROM THE ANTERIOR PITUITARY. THERE ARE FUNDAMENTAL DIFFERENCES BETWEEN OUR CHT CONSTRUCTS AND THE NATIVE OVARY (E.G., LACK OF OOCYTES IN OUR CONSTRUCTS) BUT OVARIAN, PITUITARY, AND POSSIBLY HYPOTHALAMIC HORMONES ARE REGULATED IN A MANNER SIMILAR TO A PRE-OVARIAN FAILURE STATE. THESE CELL-BASED CONSTRUCTS ALSO RELEASE OTHER HORMONES NATURALLY SECRETED BY NATIVE OVARIES BUT NOT PRESENT IN PHT. MORE IMPORTANTLY, CHT ACHIEVED BENEFICIAL BONE OUTCOMES IN A MANNER THAT WAS SAFER THAN PHT. THE LONG-TERM GOAL OF THIS RESEARCH IS TO DEVELOP A CELL-BASED THERAPY THAT CAN BE USED IN HUMANS FOR THE PREVENTION OF OSTEOPOROSIS ASSOCIATED WITH LOSS OF OVARIAN FUNCTION IN WOMEN. IN OUR PRELIMINARY STUDIES, WE HAVE ASSESSED CHT BY USING ISOGENEIC CELLS IN A RAT MODEL. HOWEVER, TO ACHIEVE CLINICAL TRANSLATION IT IS NECESSARY TO (1) UNDERSTAND HOW THE CHT DOSE AND TIMING OF IMPLANTATION AFFECTS SAFETY AND BONE HEALTH, (2) IDENTIFY SUITABLE HUMAN, ALLOGENEIC, AND/OR XENOGENEIC CELL SOURCES FOR CHT AND (3) UNDERSTAND HOW CHT ACHIEVES ITS EFFECTS AT BOTH A CELLULAR AND SYSTEMIC LEVEL. WE WILL ALSO DETERMINE THE MAXIMUM DURATION OF TIME THAT CHT CAN SECRETE OVARIAN HORMONES AND REGULATE OTHER HORMONES OF THE HPO AXIS. THE PROPOSED EXPERIMENTS WILL BE CONDUCTED PRIMARILY IN A RAT SURGICAL MODEL OF OVARIAN FAILURE TO INDUCE OSTEOPOROSIS (OVARIECTOMY; OVX). HOWEVER, AS A FIRST STEP TOWARDS CLINICAL TRANSLATION WE ALSO PROPOSE THE USE OF A LARGER, RABBIT MODEL OF OVARIAN FAILURE AND OSTEOPOROSIS (OVX WITH GLUCOCORTICOID DELIVERY). CHT WILL BE DIRECTLY COMPARED TO PHT AND TO ALENDRONATE, A BISPHOSPHONATE DRUG WIDELY PRESCRIBED TO TREAT OSTEOPOROSIS. WE WILL ALSO COMPARE CHT (AND CONTROLS) TO UNTREATED OVX ANIMALS AND TO RATS THAT HAVE NOT RECEIVED AN OVX (HEALTHY, AGE-MATCHED RATS). WE WILL PROPOSE THREE EXPERIMENTAL AIMS: AIM 1. DETERMINE EFFECT OF ISOGENEIC CHT DOSE AND IMPLANT TIMING ON HPO HORMONE LEVELS, SAFETY AND BONE HEALTH IN RAT OVX MODEL. AIM 2. ASSESS HPO HORMONE LEVELS, IMMUNE RESPONSE, SAFETY AND BONE HEALTH IN TWO OVARIAN FAILURE MODELS OF OSTEOPOROSIS WITH ISOGENEIC, ALLOGENEIC OR HUMAN CHT TREATMENT. AIM 3. DETERMINE DIFFERENTIAL GENE EXPRESSION (DGE) PROFILES FOR ISOGENEIC, ALLOGENEIC, AND HUMAN CHT TO IDENTIFY KEY FUNCTIONAL PATHWAYS AND ANY TIME-DEPENDENT CHANGES IN VITRO AND IN A RAT OVX MODEL. COMPLETION OF THESE STUDIES WILL DEMONSTRATE THE SAFETY AND EFFICACY OF THESE TISSUE-ENGINEERED CONSTRUCTS AS A POTENTIAL TREATMENT FOR OSTEOPOROSIS AND PROVIDE INFORMATION ON THEIR MECHANISMS OF ACTION.

DESIGN RESEARCH ON THE TEACHING AND LEARNING OF CONCEPTUAL UNDERSTANDING IN HIGH SCHOOL CHEMISTRY THOUGH THE USE OF DYNAMIC VISUALIZATIONS OF PHYSICAL AND CHEMICAL CHANGES

SAVING SPECIES: SOCIALLY-NETWORKED EXHIBITS FOR SCIENCE INQUIRY AND PUBLIC ACTION

THE ROLE OF INJURY SIGNALS IN RPE REPROGRAMMING

PREPARING ENGLISH LEARNER EDUCATIONAL ALLIES (¡PELEA! FIGHT!)

ELUCIDATING THE MECHANISTIC DETAILS OF THE GRP94 MOLECULAR CHAPERONE THROUGH AN INTEGRATED COMPUTATIONAL AND EXPERIMENTAL APPROACH - PROJECT SUMMARY/ABSTRACT CHAPERONE PROTEINS ARE CRITICAL FOR CELL SURVIVAL AND PROVIDE PATHWAYS FOR CORRECT PROTEIN FOLDING WITHIN THE CELL. OUR RESEARCH FOCUSES ON ATP-DEPENDENT CHAPERONES IN THE ENDOPLASMIC RETICULUM, SPECIFICALLY GRP94. GRP94 BELONGS TO THE HIGHLY CONSERVED HSP90 SUPERFAMILY, AND LIKE ITS CYTOSOLIC AND MITOCHONDRIAL PARALOGS, IT FOLDS AND ACTIVATES SPECIFIC CLIENT PROTEINS. GRP94 IS OF FUNDAMENTAL INTEREST BECAUSE IT HAS LIMITED MECHANISTIC INFORMATION COMPARED TO OTHER PARALOGS. GRP94 IS ALSO UNIQUE BECAUSE IT HAS SEVERAL OBSERVED STRUCTURAL AND FUNCTIONAL DIFFERENCES FROM PARALOGS THAT MAKE IT A PROMISING DRUG TARGET. DESPITE THE IMPORTANCE OF GRP94 CHAPERONING IN PROTEIN HOMEOSTASIS, THE FUNDAMENTAL DETAILS OF ITS CHAPERONE CYCLE ARE NOT WELL CHARACTERIZED. GRP94 IS OF PRACTICAL INTEREST SINCE ABERRANT PROTEIN FOLDING IN THE ENDOPLASMIC RETICULUM RESULTS IN MEDICAL ISSUES SUCH AS TYPE 2 DIABETES, CANCER, HEPATITIS B & C, AND NEURODEGENERATIVE AND CARDIOVASCULAR DISEASES. UNDERSTANDING GRP94’S STRUCTURE AND FUNCTION WILL PROVIDE A FOUNDATION FOR UNDERSTANDING HOW DISEASES CAUSED BY MISFOLDED ER PROTEINS CAN BE TREATED AND PREVENTED. THIS FUNDAMENTAL KNOWLEDGE OF GRP94 MECHANISMS CAN AID IN RATIONAL DRUG DESIGN. CURRENT STRATEGIES INVOLVE ATP-COMPETITIVE INHIBITORS THAT TARGET ALL HSP90 PARALOGS AND INHIBIT BOTH PRODUCTIVE AND UNPRODUCTIVE CHAPERONE ACTIVITY, WHICH RESULTS IN TOXICITY. NOVEL THERAPEUTIC STRATEGIES INCLUDE INHIBITING CHAPERONING OF TOXIC PROTEINS WHILE RETAINING CHAPERONING OF NON-TOXIC PROTEINS AND TARGETING SPECIFIC HSP90 PARALOGS; HOWEVER, MECHANISTIC INFORMATION IS REQUIRED TO MOVE THE FIELD IN THIS DIRECTION. THEREFORE, THE STUDIES OF THIS CHAPERONE MECHANISM WILL BE OF IMMENSE PRACTICAL AND ECONOMICAL VALUE IN THE DEVELOPMENT OF DISEASE THERAPIES. UNDERSTANDING THE CONFORMATIONAL CHANGES INVOLVED IN THE CHAPERONE CYCLE IS FUNDAMENTALLY IMPORTANT FOR IDENTIFYING POINTS OF INTERVENTION. UNDERSTANDING HOW CLIENT PROTEINS AND OTHER CHAPERONES STRUCTURALLY AND FUNCTIONALLY INTERACT IS FUNDAMENTALLY IMPORTANT FOR DESIGNING COMPETITIVE MODULATORS OF GRP94. MY LAB WILL DEVELOP NOVEL TECHNIQUES FOR FUNCTIONAL AND STRUCTURAL STUDIES OF GRP94. WE WILL TIGHTLY COUPLE EXPERIMENTAL AND COMPUTATIONAL STUDIES, WHICH IS A POWERFUL COMBINATION OF TOOLS THAT WILL ENABLE US TO ELUCIDATE MOLECULAR DETAILS THAT WOULDN’T BE POSSIBLE TO OBTAIN WITH EITHER METHOD INDIVIDUALLY. USING THIS APPROACH, WE WILL ANSWER THE FOLLOWING PERTINENT BIOLOGICAL QUESTIONS: (1) WHAT ARE THE PREFERRED CONFORMATIONAL STATES OF GRP94 AND WHICH CONFORMATIONS CO-EXIST IN EQUILIBRIUM? (2) HOW DO CELLULAR CONDITIONS AND INTERACTORS INFLUENCE GRP94’S CONFORMATIONAL SAMPLING? (3) WHAT TYPE OF CHAPERONE ACTIVITY DOES GRP94 DEMONSTRATE AND WHAT ARE THE REQUIREMENTS? (4) WHERE DO CLIENT PROTEINS INTERACT ON GRP94? (5) ARE ATP HYDROLYSIS EVENTS IN THE GRP94 DIMER SYMMETRIC OR ASYMMETRIC? THE SUCCESSFUL COMPLETION OF THESE STUDIES IS EXPECTED TO HAVE AN IMPORTANT IMPACT IN DECONVOLUTING THE GRP94 CHAPERONE MECHANISM, THE STRUCTURAL CHANGES INVOLVED, AND THE DETAILS OF SUBSTRATE PROTEIN INTERACTIONS AND PROCESSING. THIS INFORMATION WILL FACILITATE IN FINDING NEW AND NOVEL POINTS OF INTERVENTION TO AMELIORATE DISEASE.

EXPLOITING CANCER METABOLISM AND DRUG EFFLUX WITH BYSTANDER-ASSISTED IMMUNOTHERAPY

SUPPORTING STUDENT SUCCESS AND HIGHER DEGREE ATTAINMENT IN ENGINEERING: A SCHOLARSHIP-BASED, COMPREHENSIVE STRATEGY FOR TALENTED LOW-INCOME STUDENTS

A ROADMAP TO UNCOVER RPE PLASTICITY - ABSTRACT DEGENERATIVE RETINAL DISEASES REPRESENT AN ENORMOUS PUBLIC HEALTH BURDEN AND DEMAND INNOVATIVE STRATEGIES TO REPLACE RETINAL NEURONS. IDEAL SOLUTIONS WILL OVERCOME INNATE BARRIERS ASSOCIATED WITH TERMINAL DIFFERENTIATION TO ENDOGENOUSLY REGENERATE RETINAL NEURONS. RETINAL PIGMENT EPITHELIUM (RPE) CELLS HOLD PROMISE FOR THIS APPLICATION, AS THESE CELLS CAN REPROGRAM TO PRODUCE NEURAL RETINA IN EMBRYONIC AMNIOTES. FOR REASONS THAT ARE NOT WELL UNDERSTOOD, RPE CELLS LOSE NEURAL COMPETENCE DURING EARLY AMNIOTIC DEVELOPMENT. THE PRESENT STUDY PROPOSES TO COMPREHENSIVELY MAP THE GENE REGULATORY LANDSCAPE OF RPE AT PLASTIC STAGES OF DEVELOPMENT AND TO PROBE THE MOLECULAR BARRIERS TO REPROGRAMMING THAT EMERGE AS THESE CELLS DIFFERENTIATE. RPE CELLS OF THE CHICKEN ARE PLASTIC AT EMBRYONIC DAY 4 (E4) AND CAN BE REPROGRAMMED TO NEURAL RETINA FOLLOWING RETINECTOMY AND TREATMENT WITH FGF2. HOWEVER, BY EMBRYONIC DAY 5 (E5), RPE CELL FATE BECOMES RESTRICTED AND REPROGRAMMING CAPACITY IS ABROGATED. PREVIOUS STUDIES HAVE DEMONSTRATED THAT E4 RPE CELLS REPROGRAM THROUGH THE ACTIVATION OF NEURAL RETINA TRANSCRIPTION FACTORS, SUCH AS VSX2, SIX6, AND PAX6, AND THE SIMULTANEOUS REPRESSION OF RPE DIFFERENTIATION PROGRAMS. CONCOMITANTLY, AN EPIGENETIC REPROGRAMMING EVENT RESETS DNA METHYLATION AND POISES CHROMATIN INTO A MORE ACTIVE CONFIGURATION TO FACILITATE THE ENSUING CHANGE IN CELL IDENTITY. HOWEVER, IT IS NOT UNDERSTOOD HOW TRANSCRIPTION FACTOR NETWORKS INTERACT WITH A DYNAMIC CHROMATIN LANDSCAPE TO DETERMINE RPE NEURAL COMPETENCE. OUR PRELIMINARY EVIDENCE SUGGESTS THAT PRO-NEURAL GENES REMAIN COMPARABLY INDUCIBLE IN THE E5 RPE, BUT THAT AN INCIPIENT RPE DIFFERENTIATION PROGRAM SERVES AS AN INHERENT BARRIER TO NEURAL IDENTITY AT THIS STAGE. THIS DIFFERENTIATION PROGRAM IS LED BY THE RPE TRANSCRIPTION FACTORS MITF AND OTX2, AND DISTINCT ACCESSIBILITY FOOTPRINTS FROM THESE FACTORS ARE OBSERVABLE IN THE CHROMATIN LANDSCAPE. THE CURRENT PROPOSAL WILL BUILD ON THESE FINDINGS BY MAPPING GENOME-WIDE EPIGENETIC PATTERNS ASSOCIATED WITH RPE COMPETENCE RESTRICTION, INCLUDING DNA AND HISTONE MODIFICATIONS THAT HAVE BEEN PREVIOUSLY DEMONSTRATED TO FACILITATE RPE REPROGRAMMING (AIM 1). ADDITIONALLY, RPE DIFFERENTIATION AND REPROGRAMMING WILL BE PROFILED AT A SINGLE CELL RESOLUTION, ENABLING THE PRECISE IDENTIFICATION OF TRANSCRIPTOMIC FEATURES THAT DELINEATE PLASTIC AND FATE RESTRICTED RPE (AIM 2). IN PARALLEL, THE DNA BINDING ACTIVITY OF KEY EFFECTOR TRANSCRIPTION FACTORS, SUCH AS MITF AND OTX2, WILL BE PROFILED ACROSS THE RPE AT DIFFERENT STAGES OF DIFFERENTIATION OR REPROGRAMMING. THESE FACTORS, AS WELL AS KEY TRANSCRIPTIONAL TARGETS, WILL BE PERTURBED USING CRISPR-CAS9 WITH THE INTENTION OF RECOVERING RPE NEURAL COMPETENCE AT MORE ADVANCED STAGES OF DIFFERENTIATION (AIM 3). TOGETHER, THESE FINDINGS WILL PROVIDE AN EXPANSIVE VIEW OF CHROMATIN STATES ASSOCIATED WITH RPE COMPETENCE RESTRICTION, WHILE SIMULTANEOUSLY PROBING THE CHROMATIN – TRANSCRIPTION FACTOR INTERACTIONS THAT DRIVE THE OBSERVED PHENOTYPES. THESE RESULTS WILL PROVIDE IMPERATIVE INSIGHTS TOWARD UNDERSTANDING RPE DIFFERENTIATION AND THE POTENTIALITY OF THIS CELL TYPE FOR USE IN NEURON REPLACEMENT STRATEGIES.

EDUCATION RESEARCH PROGRAM

GRAM-NEGATIVE BACTERIAL WOUND INFECTIONS

ENGLISH LANGUAGE ACQUISITION: NATIONAL PROFESSIONAL DEVELOPMENT PROGRAM

TAS::89 0227::TAS RECOVERY;NEW-EARLY CAREER:RECOVERY ACT- THYLAKOID ASSEMBLY AND FOLDED PROTEIN TRANSPORT BY THE TAT PATHWAY; PI - CAROLE DABNEY-SMIT

COLLABORATIVE RESEARCH: FURTHER DEVELOPMENT AND TESTING OF THE TARGET INQUIRY MODEL FOR MIDDLE AND HIGH SCHOOL SCIENCE TEACHER PROFESSIONAL DEVELOPME

KERATIN HYDROGEL MATRIX FOR TUNABLE GROWTH FACTOR DELIVERY IN BONE REGENERATION

MIAMI UNIVERSITY REGIONAL CAMPUSES STUDENT SUPPORT SERVICES PROGRAM 2020-2025

MIAMI UNIVERSITY REGIONAL CAMPUSES UPWARD BOUND PROGRAM

EPR AND SOLID-STATE NMR STUDIES OF INTEGRAL MEMBRANE PROTEINS

CHEMISTRY EDUCATION RESEARCH DOCTORAL SCHOLARS PROGRAM

EPR STRUCTURAL STUDIES OF KCNE1/KCNQ1

MEASURING CHEMISTRY STUDENTS' UNDERSTANDINGS OF MULTIPLE EXTERNAL REPRESENTATIONS THROUGH CLUSTER ANALYSIS

A MIXED-METHODS STUDY OF MIDDLE-AGED AND OLDER ADULTS: LIFELONG LEARNING, SKILL PROFICIENCIES, AND EMPLOYMENT IN THE U.S. AND SELECTED OECD COUNTRIES

MIAMI UNIVERSITY REGIONAL CAMPUSES UPWARD BOUND PROGRAM

STUDY OF IRON ACQUISITION IN ACINETOBACTER BAUMANNII

UPON SOLVING THE SECRETS FOR LENS TRANSDIFFERENTIATION - ABSTRACT URODELE NEWTS ARE THE UNRIVALED CHAMPIONS OF VERTEBRATE TISSUE REGENERATION. A GREATER UNDERSTANDING OF THE PROCESSES WHICH ENABLE THEIR REGENERATIVE CAPABILITIES COULD INSPIRE NOVEL THERAPEUTIC APPROACHES TO COMBATING BLINDING AILMENTS. AFTER INJURY, THE SPANISH RIBBED NEWT PLEURODELES WALTL CAN REGENERATE ITS LENS THROUGH THE TRANSDIFFERENTIATION OF IRIS PIGMENT EPITHELIUM CELLS (IPECS) INTO LENS PROGENITOR CELLS. INTERESTINGLY, THIS REGENERATIVE COMPETENCE IS RESTRICTED TO IPECS WITHIN THE DORSAL COMPARTMENT OF THE IRIS. VENTRAL IPECS ARE NOMINALLY REGENERATION-INCOMPETENT, DESPITE BEING MORPHOLOGICALLY INDISTINGUISHABLE FROM THEIR DORSAL COUNTERPARTS. PAST EFFORTS TO IDENTIFY MOLECULAR DISTINCTIONS BETWEEN DORSAL AND VENTRAL IPECS HAVE BEEN UNABLE TO PINPOINT THE PRECISE DETERMINING FACTORS FOR REGENERATION COMPETENCE. THESE LIMITATIONS WERE IN PART OWING TO THE LARGE GENOMES OF AMPHIBIANS, WHICH HAVE PRECLUDED THE ROBUST DELINEATION OF GENE STRUCTURES. MORE RECENTLY, OUR GROUP HAS BEGUN TO ADDRESS THESE LIMITATIONS IN PLEURODELES WALTL, WHICH NOW HAS AN AVAILABLE REFERENCE GENOME. OUR PRELIMINARY OBSERVATIONS SUGGEST THAT THE MOLECULAR FOUNDATIONS OF IPEC REGENERATIVE COMPETENCE ARE DETERMINED BY A HIGHLY CONSERVED SIGNALING AXIS RELATING TO VERTEBRATE EYE DEVELOPMENT, INCLUDING BMP AND EPHRIN SIGNALING CUES. UPON SURGICAL REMOVAL OF THE LENS, WE DEMONSTRATE THAT THE NEWT IRIS UNDERGOES DISTINCT SHIFTS IN THE LOCALIZATION OF BMP SIGNALING EFFECTORS, SERVING AS A MOLECULAR “SWITCH” FOR REGENERATION COMPETENCE. SUBSEQUENTLY, THE LOCAL ENVIRONMENT OF THE DORSAL IRIS IS TRANSFORMED INTO A PRO-REGENERATIVE NICHE, WHEREAS THE VENTRAL IRIS IS CHARACTERIZED BY AN ACUTE INJURY-RESPONSE PROGRAM. FURTHERMORE, WE DEMONSTRATE THAT PHARMACOLOGIC PERTURBATION OF BMP OR EPHRIN SIGNALING IS SUFFICIENT TO CONFER REGENERATIVE COMPETENCE TO VENTRAL IPECS. THESE RESULTS COLLECTIVELY LEAD US TO HYPOTHESIZE THAT NEWT LENS REGENERATION IS DIRECTED BY A UNIQUE GENE REGULATORY PARADIGM THAT EVOLVED DOWNSTREAM OF THE CONSERVED BMP AND EPHRIN SIGNALING AXES. TO INVESTIGATE THIS CONJECTURE, WE PROPOSE TO COMPREHENSIVELY INTERROGATE THE ROLE OF THESE SIGNALING AXES IN DIRECTING DORSAL AND VENTRAL IPEC INJURY RESPONSES. GENE REGULATORY MECHANISMS, INCLUDING CHROMATIN ACCESSIBILITY PROFILING, WILL BE PERFORMED ON DORSAL AND VENTRAL IRISES AT LANDMARK TIME POINTS DURING LENS REGENERATION (AIM 1). MOREOVER, WE WILL CONSTRUCT A SPATIOTEMPORAL ATLAS OF CELL TYPES ASSOCIATED WITH THE REGENERATIVE DORSAL IRIS AND NON-REGENERATIVE VENTRAL IRIS BY LEVERAGING CUTTING-EDGE TECHNIQUES, INCLUDING SINGLE- NUCLEUS RNA SEQUENCING AND SPATIAL TRANSCRIPTOMICS (AIM 2). FINALLY, WE WILL SYSTEMATICALLY PERTURB THE BMP AND EPHRIN PATHWAYS DURING LENS REGENERATION BY USING IN VIVO SCREENS FOR DRUGGABLE NODES WITHIN THESE SIGNALING CASCADES AS WELL AS TRANSGENIC NEWT LINES (AIM 3). COLLECTIVELY, THESE FINDINGS WILL GREATLY EXPAND OUR KNOWLEDGE OF THE CELLULAR AND MOLECULAR DETERMINANTS FOR REGENERATION COMPETENCE. WE ARE HOPEFUL THAT THE PROPOSED EXPERIMENTATION HAS THE POTENTIAL TO UNCOVER NOVEL ROUTES FOR THE INDUCTION OF TISSUE REGENERATION AS A METHOD TO COMBAT EYE DISEASES.

NEW AWARD TO MIAMI UNIVERSITY FOR ITS PROJECT ENTITLED A BIOMIMETIC APPROACH TO NEW ADSORPTIVE CARBONACEOUS HYDROGEN STORAGE MATERIALS

SIGNALING PATHWAYS DURING CHICK RETINA REGENERATION

STUDENT SUPPORT SERVICES PROGRAM

A COMMUNITY-BASED AND CULTURALLY RESPONSIVE APPROACH TO STEM TEACHER PREPARATION, INDUCTION AND RETENTION

ON DETERMINANTS OF LENS REGENERATION

CAREER:WHY ARE SPECIES WHERE THEY ARE? IDENTIFYING THE INTERPLAY OF THE EVOLUTIONARY, ENVIRONMENTAL, AND BIOTIC MECHANISMS DRIVING NICHE DIVERSIFICATION IN OEDIPODINAE GRASSHOPPERS -THIS AWARD IS FUNDED IN WHOLE OR IN PART UNDER THE AMERICAN RESCUE PLAN ACT OF 2021 (PUBLIC LAW 117-2). THE GEOGRAPHIC RANGE OF A SPECIES IS ONE OF ITS MOST IMPORTANT CHARACTERISTICS. SUCH A RANGE IS PRIMARILY DETERMINED BY THE ECOLOGICAL NICHE OF THE SPECIES, WHICH REPRESENTS THE ENVIRONMENTAL CONDITIONS (SUCH AS TEMPERATURE, PRECIPITATION, OR VEGETATION) THAT ARE SUITABLE FOR THE SPECIES AND ALLOW IT TO SURVIVE AND REPRODUCE. FOR EXAMPLE, THE ECOLOGICAL NICHE OF THE INDIAN TIGER IS REPRESENTED BY HIGH TEMPERATURE, HIGH PRECIPITATION, AND DENSE VEGETATION. SOMETIMES, SIMILAR SPECIES HAVE VERY DIFFERENT ECOLOGICAL NICHES. THE ECOLOGICAL NICHE OF THE SNOW LEOPARD IS VERY DIFFERENT FROM THAT OF THE TIGER, EVEN THOUGH THE TWO SPECIES ARE CLOSELY RELATED. WHEN ECOLOGICAL NICHES DIFFER BETWEEN TWO RELATED SPECIES, IT CAN BE SAID THAT THESE ECOLOGICAL NICHES HAVE DIVERGED. BUT HOW MUCH AND IN WHAT WAYS DO ECOLOGICAL NICHES DIVERGE BETWEEN TWO SIMILAR SPECIES? HERE, THE RESEARCHER WILL EXPLORE NICHE DIVERGENCE AMONG MORE THAN 150 SPECIES OF GRASSHOPPERS FROM THROUGHOUT NORTH AMERICA. THE KNOWLEDGE AND TOOLS GAINED FROM THIS PROJECT WILL BE APPLICABLE TO A BROAD VARIETY OF QUESTIONS RELATED TO IMPORTANT TOPICS, SUCH AS SPECIES DIVERSITY (WHY ARE THERE SO MANY SPECIES IN THE TROPICS?), SPECIES CONSERVATION (HOW MUCH CHANGE IN ENVIRONMENTAL CONDITIONS CAN A SPECIES ENDURE?), OR HUMAN HEALTH (CAN A TROPICAL DISEASE SPREAD TO AREAS WITH MODERATE CLIMATES?). THE PROJECT WILL PROVIDE RESEARCH AND EDUCATIONAL OPPORTUNITIES IN STATE-OF-THE-ART METHODS IN ECOLOGY AND EVOLUTION AT THE HIGH SCHOOL, UNDERGRADUATE, GRADUATE, AND POSTDOCTORAL LEVELS. DESPITE THE IMPORTANCE OF UNDERSTANDING NICHE DIVERGENCE IN THE FIELDS OF ECOLOGY AND EVOLUTION, QUANTITATIVE AND QUALITATIVE CHARACTERISTICS OF NICHE DIVERGENCE AND THE MECHANISMS THAT DRIVE THEIR EVOLUTION HAVE NOT BEEN EXPLORED IN A COMPREHENSIVE WAY. THIS RESEARCH WILL ADDRESS KNOWLEDGE GAPS VIA A NEW THEORETICAL AND ANALYTICAL FRAMEWORK TO CLASSIFY AND QUANTIFY ECOLOGICAL NICHE DIVERGENCE BETWEEN TAXA. THIS NEW CLASSIFICATION SYSTEM 1) PROMISES TO ENHANCE UNDERSTANDING OF DIFFERENT TYPES OF NICHE DIVERGENCE; 2) CAN BE APPLIED TO ANY ECOSYSTEM OR GROUP OF ORGANISMS; AND 3) CAN BE USED TO ADDRESS A BROAD VARIETY OF ECOLOGICAL AND EVOLUTIONARY QUESTIONS. THE FRAMEWORK WILL BE USED TO EXPLORE THE EVOLUTIONARY, ENVIRONMENTAL, AND BIOTIC FACTORS DRIVING NICHE DIVERGENCE IN GRASSHOPPERS IN THE SUBFAMILY OEDIPODINAE, AS A MODEL SYSTEM. SPECIFIC EDUCATIONAL GOALS INCLUDE ADVANCING BIOINFORMATICS LITERACY NECESSARY FOR SUCCESS IN STEM FIELDS, PROVIDING APPLIED SKILLS TO WORK WITH A VARIETY OF BIG DATA, AND TRAINING STUDENTS IN INTERDISCIPLINARY, INTEGRATIVE APPROACHES FOR UNDERSTANDING PATTERNS OF BIODIVERSITY AND ADVANCING CONSERVATION. 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.

URM: ACHIEVING SUCESS IN SCIENCE THROUGH UNDERGRADUATE RESEARCH EXPERIENCES (ASSURE)

FIGHTING WITH FOOD: BATTLING CHEMICAL TOXICITY WITH GOOD NUTRITION

FUND FOR THE IMPROVEMENT OF EDUCATION - PRESIDENTIAL/CONGRESSIONAL ACADEMIES FOR TEACHING OF AMERICAN HISTORY AND CIVICS

DETERMINING THE MECHANISM OF INHIBITION OF METALLO-B-LACTAMASE INHIBITORS

GLIDING MOTILITY AND CYTADHERENCE IN MYCOPLASMA PENETRANS

A BIOPSYCHOSOCIAL MODEL OF EMOTION PROCESSES DETERMINING THE ROLE OF OVERCONTROLL

MRI: ACQUISITION OF A PULSED ELECTRON PARAMAGNETIC RESONANCE (EPR) SPECTROMETER

TEXT MESSAGE SUPPORT TO PREVENT SMOKING RELAPSE IN COMMUNITY TREATMENT SETTINGS

CENTRAL ACTION OF BRAIN-DERIVED NEUROTROPHIC FACTOR IN MALE AND FEMALE RATS

EXPANDQISE: TRACK 1: A DEEP-DIVE INTO THE MATERIALS SCIENCE OF ALPHA-TA GROWTH ON OXIDES FOR SUPERCONDUCTING RESONATOR DEVELOPMENT -NON-TECHNICAL ABSTRACT: QUANTUM COMPUTERS CAN POTENTIALLY MAKE REVOLUTIONARY CHANGES IN HOW COMPUTERS FUNCTION AND HOW COMPUTING ALGORITHMS ARE DESIGNED. TRADITIONAL COMPUTERS UTILIZE A ?BIT? TO COMPUTE AND PROCESS INFORMATION, CREATING A COMPUTER SPEED BOTTLENECK. QUANTUM COMPUTERS OPERATE ON A DIFFERENT KIND OF A BIT, A QUANTUM BIT, THE ?QUBIT,? WHICH CAN BE ENORMOUSLY FASTER IN COMPUTATION TIMES. SUPERCONDUCTING QUBITS ARE ONE OF THE LEADING CANDIDATES TO CREATE QUANTUM COMPUTERS WITH THE POTENTIAL TO SURPASS MODERN SUPERCOMPUTERS IN SOLVING SPECIFIC PROBLEMS. A POPULAR WAY TO CREATE A QUBIT IS TO PATTERN A QUBIT CIRCUIT ON A LOW-LOSS INSULATOR/ METAL STRUCTURE MADE OF JOSEPHSON JUNCTIONS, COPLANAR CAPACITORS, INDUCTORS, AND RESONATOR WAVEGUIDES. HOWEVER, CREATING THESE CIRCUITS FOR QUBITS INTRODUCES DISORDER INTO THE INSULATOR/METAL STRUCTURE, CAUSING ERRORS AND LOSS OF QUANTUM INFORMATION. THE RESEARCH TEAM IMPLEMENTS A HOLISTIC DEEP-DIVE OF MATERIAL SCIENCE ON THE INSULATOR/METAL STRUCTURE TO UNCOVER THE SOURCES OF THIS DISORDER TO IMPROVE THE QUALITY OF THE QUBIT CIRCUITS. THE RESEARCH TEAM SIMULTANEOUSLY IMPLEMENTS A NEW QUANTUM CURRICULUM AND A NEW QUANTUM INFORMATION SCIENCE MICRO-CREDENTIAL UTILIZING EVIDENCE-BASED TEACHING METHODS TO REACH OPTIMAL LEARNING OBJECTIVES, IMPACT THE QUANTUM EDUCATION FIELD WITH NEW TEACHING MODULES AND CLASSES, AND INCREASE PARTICIPATION IN THE QUANTUM WORKFORCE. TO THIS END, THE RESEARCH TEAM CONCURRENTLY PERFORMS PHYSICS EDUCATION RESEARCH WITHIN NEW QUANTUM SCIENCE COURSES AND MICRO-CREDENTIAL BY APPLYING EVIDENCE-BASED ACTIVE ENGAGEMENT AND BENCHMARKING LEARNING OUTCOMES VERSUS INTENDED LEARNING GOALS. THIS PROJECT IS CONDUCTED ACROSS THE COLLABORATING UNIVERSITIES AND MEASURES THE SUCCESS OF ADAPTING AN EARLY UNDERGRADUATE-LEVEL QUANTUM INFORMATION SCIENCE COURSE AND INCORPORATING ACTIVE ENGAGEMENT STRATEGIES. VITAL IMPROVEMENTS IN QUANTUM EDUCATION AND WORKFORCE DEVELOPMENT ARE MADE BY BROADENING EVIDENCE-BASED INSTRUCTION IN THE QUANTUM INFORMATION SCIENCE CURRICULUM. TECHNICAL ABSTRACT: THIS RESEARCH AIMS TO ALLEVIATE SOME OF THE MYSTERY IN TWO-LEVEL SYSTEM DISSIPATION SOURCES FOR ALPHA-TA SUPERCONDUCTING RESONATOR SYSTEMS BY PERFORMING A HOLISTIC CHARACTERIZATION OF THE DISSIPATION SOURCES AND WHERE THESE DISSIPATION SOURCES ARE INTRODUCED IN THE GROWTH AND FABRICATION PROCESS. TO THIS END, THE RESEARCH TEAM CONDUCTS A COMPREHENSIVE INVESTIGATION OF ALPHA-TA GROWN ON SEVERAL LOW-DISSIPATION INSULATING OXIDE SUBSTRATES. THE RESEARCH TEAM IDENTIFIES CRITICAL DEFECTS INTRODUCED DURING GROWTH AND SUBSEQUENTIAL DEVICE PROCESSING TO REMEDY DEFECT BOTTLENECKS THAT ADVERSELY AFFECT THE QUALITY FACTOR OF SUPERCONDUCTING RESONATOR CIRCUITS. THE TEAM SYSTEMATICALLY CORRELATES THE QUALITY FACTOR TO SPECIFIC THIN FILM SYNTHESIS PROCEDURES, MICROFABRICATION PROCEDURES, BULK MATERIAL, AND INTERFACE DEFECT TYPES IDENTIFIED IN STRUCTURAL AND CONDUCTIVE ELECTRON AND SCAN PROBE MICROSCOPY CHARACTERIZATIONS. THIS HOLISTIC MATERIALS SCIENCE DEEP-DIVE IDENTIFIES SYSTEMATIC RELATIONSHIPS BETWEEN STRUCTURE AND DISSIPATION AND POSSIBLY ESTABLISHES A ROOM-TEMPERATURE PROXY FOR LOW-TEMPERATURE SUPERCONDUCTING DEVICE PERFORMANCE. AT THE SAME TIME, THIS RESEARCH SEEKS TO INVESTIGATE THE FIDELITY OF IMPLEMENTING QUANTUM INFORMATION EDUCATION TOOLS AND FRAMEWORKS DEVELOPED TO BE ACCESSIBLE AT THE HIGH SCHOOL AND EARLY UNDERGRADUATE LEVELS. THE PROJECT WILL CONTRIBUTE TO QUANTUM EDUCATION AND WORKFORCE DEVELOPMENT THROUGH EVIDENCE-BASED INSTRUCTIONAL STRATEGIES SUCH AS IMPLEMENTING INTERACTIVE QUANTUM LEARNING TUTORIALS AND CLICKER QUESTION SEQUENCES. THIS PROJECT IS JOINTLY FUNDED BY THE OFFICE OF MULTIDISCIPLINARY ACTIVITIES (MPS/OMA), AND THE TECHNOLOGY FRONTIERS PROGRAM (TIP/TF). 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.

EXPANDQISE: TRACK 1: BRIGHT, HIGHLY POLARIZATION-SQUEEZED LIGHT BEAM FOR QUANTUM METROLOGY -NON-TECHNICAL ABSTRACT: SQUEEZED LIGHT REFERS TO QUANTUM STATES OF LIGHT IN WHICH THE NOISE FLUCTUATIONS IN CERTAIN QUADRATURE COMPONENTS OF THE ELECTRIC FIELD AMPLITUDE, OR THE POLARIZATION, ARE SQUEEZED BELOW THE SHOT-NOISE LIMIT. THIS ENABLES BETTER SIGNAL-TO-NOISE IN OPTICAL MEASUREMENTS THAN POSSIBLE WITH PERFECTLY COHERENT LIGHT EMANATING FROM THE QUIETEST LASERS. CURRENTLY, THERE IS GREAT INTEREST IN EXPLOITING THIS QUANTUM ADVANTAGE FOR PRECISION MEASUREMENT. OPTICAL MAGNETOMETERS ARE PARADIGMATIC EXAMPLES OF HIGH-PERFORMANCE MAGNETIC FIELD SENSORS THAT RELY ON THE QUANTUM ADVANTAGE AFFORDED BY POLARIZATION-SQUEEZED LIGHT. IN THIS PROJECT, A NEW DEVICE, ESSENTIALLY A MODIFIED MAGNETOMETER, IS BUILT TO GENERATE A POLARIZATION-SQUEEZED LIGHT BEAM WITH AN UNPRECEDENTEDLY HIGH DEGREE OF SQUEEZING. THE EMERGING BEAM IS ESPECIALLY SUITED FOR TRANSFORMATIVELY ADVANCING THE FIELD OF QUANTUM-ENHANCED OPTICAL MAGNETOMETRY. THE POLARIZATION-SQUEEZED BEAM MAY ALSO ENABLE SIGNIFICANT ADVANCEMENT IN MANY OTHER DIVERSE FIELDS, RANGING FROM GRAVITATIONAL-WAVE DETECTION TO QUANTUM-LIMITED CONTROL OF MECHANICAL MOTION, WHERE SQUEEZED LIGHT AFFORDS QUANTUM ADVANTAGE. A CLOSE COLLABORATION BETWEEN MIAMI UNIVERSITY, OHIO AND THE UNIVERSITY OF WISCONSIN, MADISON, LEVERAGES EXISTING EXPERTISE IN OPTICAL MAGNETOMETRY AT WISCONSIN TO SYNERGISTICALLY ENGAGE MASTERS? (MS) STUDENTS AND UNDERGRADUATES AT MIAMI AND ALSO STUDENTS AT HIGH SCHOOLS NEAR MIAMI IN INTENSIVE RESEARCH AND EDUCATION AT THE FOREFRONT OF QUANTUM METROLOGY. CONCURRENTLY, THE PROJECT DIVERSIFIES AND EXPANDS STUDENT AND FACULTY ENGAGEMENT AT MIAMI IN QUANTUM INFORMATION SCIENCE AND ENGINEERING (QISE) BY A) DEVELOPING TWO NEW QISE-CENTERED PHYSICS COURSES, ONE AT THE FRESHMAN LEVEL, THE OTHER AT THE SENIOR / FIRST-YEAR MS LEVEL, AND B) INCORPORATING KEY QISE CONCEPTS INTO MULTIPLE EXISTING PHYSICS COURSES AT ALL LEVELS THAT IMPACT SEVERAL HUNDRED SCIENCE, TECHNOLOGY, ENGINEERING, AND MATH (STEM) MAJORS PER YEAR. TECHNICAL ABSTRACT: THE GOAL OF THIS PROJECT IS TO CREATE A ROBUST AND EFFICIENT SOURCE OF POLARIZATION-SQUEEZED LIGHT TO SIGNIFICANTLY ENHANCE THE PERFORMANCE OF TWO WIDELY-USED STATE-OF-THE-ART OPTICAL MAGNETOMETERS, NAMELY, SPIN-EXCHANGE-RELAXATION-FREE (SERF) MAGNETOMETERS, WHICH ARE CURRENTLY THE MOST SENSITIVE MAGNETIC SENSORS AT EXTREMELY LOW MAGNETIC FIELDS (BELOW ONE PICOTESLA), AND BELL-BLOOM MAGNETOMETERS, WHICH OPERATE AT EARTH-SCALE MAGNETIC FIELDS. THE MIAMI-WISCONSIN TEAM?S METHOD TO CREATE HIGHLY POLARIZATION-SQUEEZED LIGHT RELIES ON EXPLOITING THE PHYSICS OF OFF-RESONANT FARADAY ROTATION IN DENSE ATOMIC VAPOR. THE KEY TO THIS METHOD IS THAT THE QUANTUM POLARIZATION FLUCTUATIONS IN THE LIGHT ARE MAPPED INTO EFFECTIVE MAGNETIC FIELD FLUCTUATIONS VIA THE AC STARK EFFECT, WHICH CAUSES THE ATOMIC SPINS TO ALTER THE SPIN-DEPENDENT INDEX OF REFRACTION IN SUCH A WAY AS TO CANCEL THE ORIGINAL QUANTUM POLARIZATION FLUCTUATIONS. THIS YIELDS HIGHLY POLARIZATION-SQUEEZED LIGHT IN A NARROW FREQUENCY BAND FROM NEAR-DC TO ABOUT A KHZ, WHERE SERF MAGNETOMETERS OPERATE. NEXT, THE LARMOR FREQUENCY RESPONSE OF THE ATOMS IS ENGINEERED TO PRODUCE SQUEEZING CENTERED AT A DESIRED RADIO FREQUENCY, WHICH HAS VITAL IMPORT FOR BELL-BLOOM MAGNETOMETERS. THE POLARIZATION SQUEEZING PROCESS IS MODELED, AND NEW THEORETICAL APPROACHES TO SQUEEZING IN OPTICAL MAGNETOMETRY ARE DEVELOPED. 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.

DEVELOPMENT OF BEAM-OFFSET OPTICAL COHERENCE TOMOGRAPHY - PROJECT SUMMARY FOR CELLULAR IMAGING IN DEEP TISSUE, ADAPTIVE OPTICS OCT (AO-OCT) HAS BEEN INTENSIVELY DEVELOPED BY RESHAPING THE WAVEFRONT OF THE ILLUMINATION BEAM TO FOCUS THE BEAM TO DIFFRACTION-LIMITED POINT SPREAD FUNCTION (PSF) IN A TARGETED REGION. DUE TO ITS COMPLEXITY, COST, AND SIZE, WAVEFRONT SENSOR-BASED AO-OCT IS CHALLENGING TO BE TRANSLATED INTO CLINICS. LESS COMPLICATED SENSORLESS AO-OCT(SAO-OCT) OPTIMIZES THE PSF USING IMAGE METRICS, BUT CANNOT ENSURE GLOBAL OPTIMIZATION AND IS SUSCEPTIBLE TO MOTION ARTIFACTS BECAUSE IMAGE METRICS MUST BE STRONG AND STEADY DURING THE OPTIMIZING ITERATION. A TRAINED ARTIFICIAL NEURON NETWORK (ANNS) CAN OPTIMIZE THE WAVEFRONT IMMEDIATELY, MUCH MORE EFFICIENTLY THAN THE CONVENTIONAL OPTIMIZATION THROUGH MULTIPLE ITERATIONS. HOWEVER, TRAINING ANNS WITH THE IMAGE METRIC LIMITS THE GENERALITY OF THE ANN. WE BELIEVE THAT THE BEST METRIC FOR SAO-OCT SHOULD BE EITHER THE PSF OR ITS FREQUENCY DOMAIN EQUIVALENT, MODULATED TRANSFER FUNCTION (MTF), AS THEY ARE THE GOALS FOR OPTIMIZATION AND ARE INDEPENDENT OF THE IMAGED SUBJECTS AND SYSTEM OPTICS. HOWEVER, THE TECHNOLOGY OF ACCESSING PSF/MTF IN A SCATTERING MEDIUM WITH OCT HAS NOT BEEN PROPOSED.OCT IMAGES ORIGINATE FROM BACKSCATTERED PHOTONS DUE TO REFRACTIVE INDEX VARIATION IN TISSUE. NEW CONTRAST, TISSUE PROPERTY-RELATED OPTICAL ATTENUATION COEFFICIENT (OAC), HAS BEEN EXTENSIVELY INVESTIGATED TO IMPROVE THE DIAGNOSTIC CAPABILITY OF OCT. HOWEVER, DERIVING OAC IS MAINLY BASED ON THE SINGLE-SCATTERING MODEL, WHICH IGNORES MSPS, AS CONVENTIONAL OCT CANNOT DISTINGUISH LSPS AND MSPS. IN ADDITION, THE SINGLE-SCATTERING MODEL RELIES ON AT LEAST THREE INTERDEPENDENT PARAMETERS. PRIOR KNOWLEDGE IS NEEDED TO ENSURE DERIVING OAC SUCCESSFULLY, BUT OBTAINING IT IN A CLINICAL SETTING IS NOT PRACTICAL. THESE LIMITATIONS HAVE PROHIBITED OAC MEASURING FROM BEING TRANSLATED INTO CLINICS. HERE, WE PROPOSE RECONSTRUCTING BACKSCATTERED PHOTON DISTRIBUTION(BPD) IN A SCATTERING MEDIUM WITH BEAM-OFFSET OCT (BO-OCT) TO RESOLVE THE ABOVE CHALLENGES. IN CONVENTIONAL OCT, THE ILLUMINATION AND DETECTION BEAMS SHARE THE SAME OPTICAL PATHS. IN BO-OCT, THE DETECTION BEAM ACQUIRES IMAGES AT OFFSET POSITIONS FROM THE ILLUMINATION BEAM. THE BPD CAN THEN BE RECONSTRUCTED WITH THE OFFSET IMAGES. OUR THEORETICAL PREDICTION AND PRELIMINARY DATA SHOW THAT THE DISTRIBUTION OF LSPS IS EQUIVALENT TO THE DEPTH-RESOLVED MTF, SUGGESTING SAO-OCT CAN BE IMPLEMENTED USING THE MTF AS THE METRIC. WITH THE BPD, WE ALSO SHOW IT IS FEASIBLE TO SEPARATE LSPS AND MSPS, ALLOWING FOR ACCURATELY RETRIEVING OAC BY USING JUST THE LSPS TO FIT THE SINGLE-SCATTERING MODEL. REAL-TIME ACCESSING FOCAL DEPTH AND RAYLEIGH RANGE THROUGH THE BPD ALLOW INCORPORATING THE VARIATION OF THESE PARAMETERS INTO MODELING, SUGGESTING A NEW METHOD IMMUNE FROM MOTION ARTIFACTS.

RULES AND CONSTRAINTS SHAPING THE EVOLUTION OF GENE REGULATORY NETWORKS -NEW BODY STRUCTURES ALLOW ORGANISMS TO EXPLORE NEW WAYS OF SURVIVING AND ADAPT TO DIFFERENT ENVIRONMENTS. UNDERSTANDING HOW SUCH STRUCTURES ARISE AT THE MOLECULAR LEVEL HAS LONG BEEN A CENTRAL GOAL IN BIOLOGY. RATHER THAN INVENTING NEW GENES TO BUILD NEW BODY FEATURES, EVOLUTION OFTEN WORKS BY REUSING EXISTING ONES, CHANGING WHEN AND WHERE GENES ARE TURNED ON AND HOW THEY INTERACT WITH EACH OTHER. THESE CHANGES IN HOW GENES INTERACT, KNOWN AS GENE REGULATORY NETWORKS, ARE NOW THOUGHT TO BE A PRIMARY DRIVER OF THE EMERGENCE OF NEW BODY FEATURES. HOWEVER, IT REMAINS UNCLEAR WHETHER THE EVOLUTION OF GENE REGULATORY NETWORKS FOLLOWS ANY PREDICTABLE TRENDS, UNDERLYING RULES, OR INHERENT LIMITATIONS. USING THE HIGHLY MODIFIED WINGS OF BEETLES AS A MODEL SYSTEM, THIS PROJECT SEEKS TO UNCOVER THE PRINCIPLES THAT GOVERN HOW GENE NETWORKS CHANGE OVER EVOLUTIONARY TIME TO GENERATE NEW STRUCTURES. BEYOND ITS SCIENTIFIC SIGNIFICANCE, THIS PROJECT ADVANCES THE BROADER NATIONAL INTEREST IN SEVERAL WAYS. THE PROJECT INTEGRATES RESEARCH AND EDUCATION BY SUPPORTING A STUDENT-DRIVEN GENE ANNOTATION INITIATIVE CONDUCTED IN THE TEACHING LABORATORY, IN WHICH UNDERGRADUATE STUDENTS PERFORM ORIGINAL GENETIC EXPERIMENTS AND CONTRIBUTE THEIR FINDINGS TO A PUBLICLY ACCESSIBLE DATABASE, GAINING REAL-WORLD RESEARCH EXPERIENCE. THE PROJECT ALSO ESTABLISHES SEVERAL SCIENCE OUTREACH INITIATIVES DESIGNED TO ENGAGE AND RECRUIT INDIVIDUALS WITH DISABILITIES INTO SCIENTIFIC CAREERS. FURTHERMORE, INSIGHTS INTO THE PRINCIPLES GOVERNING GENE NETWORK EVOLUTION DERIVED FROM THIS PROJECT HAVE RELEVANCE TO BIOTECHNOLOGY APPLICATIONS AND BIOINSPIRED ENGINEERING, INCLUDING THE RATIONAL DESIGN OF SYNTHETIC GENE CIRCUITS AND THE DEVELOPMENT OF ADAPTIVE BIOLOGICAL SYSTEMS, WITH POTENTIAL APPLICATIONS IN MEDICAL DIAGNOSTICS, BIOLOGICALLY FACILITATED ENVIRONMENTAL IMPROVEMENT, AND OPTIMIZED BIOPRODUCTION. MORPHOLOGICAL INNOVATION OFTEN ARISES FROM NOVEL USES OF EVOLUTIONARILY CONSERVED GENES, I.E., MODIFICATIONS IN GENE REGULATORY NETWORKS (GRNS). GRN MODIFICATIONS ARE OFTEN DRIVEN BY CHANGES IN ENHANCERS, WHICH CONTROL GENE EXPRESSION AND ENABLE NEW REGULATORY CONNECTIONS, BUT WHETHER THEIR EVOLUTION FOLLOWS PREDICTABLE RULES OR CONSTRAINTS REMAINS UNCLEAR. THE ELYTRON, A HIGHLY MODIFIED FOREWING UNIQUE TO BEETLES, IS A KEY MORPHOLOGICAL INNOVATION THAT SHIELDS THE BODY FROM ENVIRONMENTAL STRESSES. THIS PROJECT UTILIZES THE ELYTRON OF TRIBOLIUM CASTANEUM, A BEETLE WITH WELL-ESTABLISHED GENETIC AND GENOMIC TOOLS, TO EXPLORE PREVIOUSLY UNDEREXAMINED ASPECTS OF GRN EVOLUTION. SPECIFIC AIM 1 WILL EXPLORE HOW THE WING GENE NETWORK (WGN) IN BEETLES HAS CO-OPTED NUMEROUS EFFECTOR GENES TO PRODUCE THE PROTECTIVE SURFACE OF THE ELYTRON THROUGH GENOMIC AND ENHANCER ANALYSES, EXAMINING BOTH THE EXTENT OF CO-OPTION AND WHETHER IT IS DRIVEN BY INDIVIDUAL GENE RECRUITMENT OR COORDINATED BY AN UPSTREAM REGULATORY GENE. SPECIFIC AIMS 2 AND 3 WILL INVESTIGATE HOW THE WGN MANAGES ITS PLEIOTROPIC NATURE AND ACCOMMODATES THE CHANGES REQUIRED FOR ELYTRON DEVELOPMENT WHILE PRESERVING THE ANCESTRAL FLIGHT WING MORPHOLOGY OF THE HINDWING. SEVERAL HYPOTHESES REGARDING HOW THE FUNCTIONAL PROPERTIES OF TRANSCRIPTION FACTORS, ACTING AS ACTIVATORS OR REPRESSORS, INFLUENCE THE NETWORK EVOLUTION WILL BE TESTED THROUGH ENHANCER ANALYSIS AND NOVEL RNA INTERFERENCE (RNAI)-BASED GENETIC INTERACTION ASSAYS. THROUGH THESE AIMS, THIS PROJECT EXPLORES THE UNDERLYING PRINCIPLES AND INHERENT CONSTRAINTS GUIDING WGN EVOLUTION, PROVIDING NEW INSIGHTS INTO HOW COMPLEX GENE NETWORKS EVOLVE TO PRODUCE NOVEL MORPHOLOGICAL TRAITS WHILE OFTEN RETAINING THEIR ESSENTIAL ANCESTRAL FUNCTIONS. 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.

LTREB: RESPONSE OF A RESERVOIR ECOSYSTEM TO CHANGING SUBSIDIES OF NUTRIENTS AND DETRITUS

MIAMI UNIVERSITY: CCAMPIS SUBSIDIES FOR LOW-INCOME STUDENT-PARENTS ON THREE CAMPUSES

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

NANOSCALE ELECTROCHEMICAL MAPPING OF THE NUCLEATION AND GROWTH OF CORROSION

MRI: ACQUISITION OF A MULTI-COLLECTOR ICP-MS WITH LASER ABLATION FOR GEOCHEMICAL AND GEOCHRONOLOGICAL APPLICATIONS

REVITALIZATION OF THE ARECIBO INCOHERENT SCATTER RADAR DATA: CONTEMPORARY ANALYSES, DATABASE EXPANSION, AND MULTI-VARIABLE STUDIES OF TRAVELING IONOSPHERE DISTURBANCES -THE PROJECT SUPPORTS EFFORTS TO OBTAIN THE MOST ACCURATE IONOSPHERIC MEASUREMENTS AND USE THEM TO STUDY TRAVELING IONOSPHERE DISTURBANCES. THE FIRST OBJECTIVE OF THE PROPOSAL IS TO ANALYZE AND ARCHIVE ALL THE AVAILABLE CODED-LONG-PULSE (CLP) DATA COLLECTED BY THE ARECIBO INCOHERENT SCATTER RADAR (ISR). THE GEOPHYSICAL PARAMETERS DERIVED FROM THE CLP DATA WILL INCLUDE ION AND ELECTRON TEMPERATURES (TI, TE), VECTOR ION VELOCITY (VI), ELECTRON DENSITY (NE), AND ION COMPOSITION FROM 130 TO 650 KM. WITH ADVANCES IN COMPUTING POWER, THE RESEARCH TEAM HAS DEVELOPED AN EXHAUSTIVE FITTING METHOD USING THE ION-LINE SPECTRA TO OBTAIN TI, TE, VI, NE, AND MOLECULAR ION FRACTIONS SIMULTANEOUSLY WITH THE BEST ACCURACY YET. THE NEW METHOD WILL BE EXTENDED TO THE UPPER F-REGION TO OBTAIN HE+ AND H+ FRACTIONS AND MORE ACCURATE TI AND TE. COMBINING THE ION-LINE AND PLASMA-LINE DATA ALLOWS THE MEASUREMENT OF THE ANTENNA NEAR-FIELD GAIN FOR THE FIRST TIME SINCE 1992, WHICH MAKES IT POSSIBLE TO MEASURE NE ACCURATELY BELOW ~200 KM AND OBTAIN HIGH-RESOLUTION TE/TI. USING MODERN AI TECHNIQUES, THE TEAM EXPECTS TO INCREASE THE EFFICIENCY OF CLP NE MEASUREMENT BY 10-FOLD. THE PROJECT WILL REVITALIZE THE ARECIBO DATABASE IN TERMS OF NOT ONLY IMPROVED ACCURACY AND RESOLUTION BUT ALSO ADDITIONAL DATA TYPES NOT AVAILABLE PREVIOUSLY. OWING TO ARECIBO?S UNSURPASSED SIGNAL-TO-NOISE RATIO AND THE OPTIMIZED FITTING METHOD USED, THE NEWLY ARCHIVED DATA IS EXPECTED TO SET THE GOLD STANDARD FOR ISR-DERIVED PARAMETERS AT ARECIBO OR ELSEWHERE. THE SECOND OBJECTIVE FOCUSES ON MULTI-VARIABLE STUDIES OF TRAVELING IONOSPHERE DISTURBANCE (TID) USING THE NEWLY ANALYZED DATA. THE TEAM WILL DELINEATE THE RELATIONSHIPS BETWEEN TID?S MANIFESTATIONS IN TI, TE, VI AND NE. THE STUDY WILL PROVIDE DETAILED VERTICAL AND HORIZONTAL CHARACTERISTICS OF TID. THE AVAILABILITY OF HIGH-QUALITY DATA WILL IMPROVE OUR UNDERSTANDING OF SPACE WEATHER PHENOMENA AND CLIMATOLOGY. THE PROPOSED STUDY ON TID, A UBIQUITOUS PHENOMENON AT ARECIBO, WILL SHOWCASE ARECIBO?S CAPABILITY AND HIGHLIGHT THE COUPLING PROCESSES BETWEEN THE DIFFERENT STATE VARIABLES OVER A LARGE ALTITUDE RANGE. THE PROJECT WILL HELP TRAIN YOUNG SCIENTISTS AND STUDENTS IN RADAR SIGNAL PROCESSING AND AERONOMY. 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.

COLLABORATIVE PROJECT: REGULATION OF SUSTAINED CYCLIC ELECTRON FLOW (CEF) IN THE PHOTOPSYCHROPHILE CHLAMYDOMONAS SP. UWO241

MECHANISMS OF RAPID AND WINTER COLD-HARDENING IN INSECTS

DONOR-ACCEPTOR EXTENDED PORPHYRINS AS LIGHT HARVESTER FOR SOLAR ENERGY CONVERSION

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

HCC: MEDIUM: COLLABORATIVE RESEARCH: LOW COST PORTABLE MULTI-USER IMMERSIVE VIRTUAL ENVIRONMENT SYSTEMS FOR EDUCATION AND TRAINING IN WORLDS OF

CAREER:PROTIST NUTRITIONAL STRATEGIES IN PERMANENTLY STRATIFIED ANTARCTIC LAKES

ADENOVIRUS ACTIVATION OF CELLULAR DNA DAMAGE RESPONSES

TAS:: 57 3600::TAS SATELLITE SIGNAL PARAMETER ESTIMATION ALGORITHMS FOR HIGH-ACCURACY APPLICATIONS

AN INTEGRATED PROJECT ON ARECIBO INCOHERENT SCATTER RADAR DATA PROCESSING, ARCHIVING AND INVESTIGATION OF IONOSPHERE DYNAMICS, ENERGETICS AND COMPOSITION

EARLY LIFE ANTECEDENTS PREDICTING ADULT DAILY AFFECTIVE REACTIVITY TO STRESS -WHEN PEOPLE EXPERIENCE STRESS, THEIR POSITIVE EMOTIONS (E.G., JOY, EXCITEMENT, CONTENTMENT) OFTEN DECREASE, AND THEIR NEGATIVE EMOTIONS (E.G., ANXIETY, FRUSTRATION, AND ANGER) TEND TO INCREASE. HOWEVER, PEOPLE VARY IN HOW MUCH THEIR EMOTIONS CHANGE WITH STRESS. THIS IS CALLED DAILY AFFECTIVE REACTIVITY TO STRESS. HAVING GREATER AFFECTIVE REACTIVITY IS ASSOCIATED WITH POOR OUTCOMES INCLUDING WORSE WELL-BEING, HIGHER RISKS OF MENTAL AND PHYSICAL HEALTH PROBLEMS, AND DYING EARLIER. THIS PROJECT INVESTIGATES WHETHER AND HOW EXPERIENCES DURING CHILDHOOD, SUCH AS EXPERIENCING MALTREATMENT AND STRESS OR RECEIVING HIGH QUALITY PARENTING, PREDICT DAILY AFFECTIVE REACTIVITY TO STRESS IN ADULTHOOD. THIS PROJECT ALSO INVESTIGATES HOW THE USE OF COPING STRATEGIES IN ADULTHOOD, SUCH AS SEEKING SUPPORT, EXERCISING, OR USING DRUGS OR ALCOHOL, MIGHT CHANGE OR EXPLAIN THE LINKS BETWEEN CHILDHOOD EXPERIENCES AND DAILY AFFECTIVE REACTIVITY TO STRESS IN ADULTHOOD. THE RESEARCH INFORMS THE DESIGN OF EFFECTIVE INTERVENTIONS FOR HELPING PEOPLE RESPOND CONSTRUCTIVELY TO DAILY STRESS. THIS PROJECT BUILDS ON THE MINNESOTA LONGITUDINAL STUDY OF RISK AND ADAPTATION, A LONGITUDINAL STUDY THAT HAS FOLLOWED A SAMPLE OF PEOPLE BORN INTO POVERTY FOR OVER 50 YEARS. NOW, WITH PARTICIPANTS AT AGE 50, THIS PROJECT HAS THEM COMPLETE 14 DAILY SURVEYS REFLECTING ON THE STRESSFUL EVENTS THAT OCCUR EACH DAY AND HOW THEY RESPOND IN TERMS OF POSITIVE AND NEGATIVE AFFECT, SUPPORT SEEKING, SUBSTANCE USE, AND EXERCISE. THESE DATA ARE USED TO TEST WHETHER EARLY EXPERIENCES PREDICT DAILY AFFECTIVE REACTIVITY TO STRESS BY LOOKING AT MEASURES OF MALTREATMENT, LIFE STRESS, AND MATERNAL SENSITIVITY THAT WERE COLLECTED DURING THE PARTICIPANTS? INFANCY AND CHILDHOOD. TWO COMPETING THEORETICAL MODELS OF HOW EARLY EXPERIENCES SHAPE ADULT STRESS REACTIVITY ARE TESTED. THE STRESS SENSITIZATION MODEL PROPOSES THAT ADVERSE EARLY EXPERIENCES LEAD TO GREATER REACTIVITY TO STRESSORS IN ADULTHOOD, WITH POSITIVE EARLY EXPERIENCES HAVING PROTECTIVE EFFECTS. THE STRESS INOCULATION MODEL PROPOSES THAT INDIVIDUALS WITH VERY HIGH OR VERY LOW EARLY ADVERSITY WILL BE MORE REACTIVE TO STRESS IN ADULTHOOD, AND INDIVIDUALS WHO EXPERIENCE MODERATE EARLY ADVERSITY WILL BE LESS REACTIVE TO STRESS. DETAILED ANALYSES OF MODERATION AND MEDIATION EFFECTS DETERMINE WHETHER TENDENCIES TO ENGAGE IN SUPPORT SEEKING, EXERCISE, AND SUBSTANCE USE IN RESPONSE TO STRESS CHANGE OR EXPLAIN LINKS BETWEEN EARLY EXPERIENCES AND DAILY AFFECTIVE REACTIVITY TO STRESS. RESULTS ARE SHARED WITH INTERVENTION AND POLICY ORGANIZATIONS TO ENCOURAGE APPLICATION. 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.

INVESTIGATION OF MAGNETIC ANISOTROPY AND SPIN WAVE MODES IN TRANSITION METAL

SEX CHROMOSOME CONTRIBUTIONS TO ALCOHOL DRINKING BEHAVIORS - PROJECT SUMMARY MEN AND WOMEN HAVE DIFFERING VULNERABILITIES TO ALCOHOL. FOR EXAMPLE, MEN DEVELOP ALCOHOL USE DISORDER AT HIGHER RATES BUT RESEARCH SHOWS THAT WOMEN MAY ESCALATE THEIR DRINKING FASTER AND BE MORE MOTIVATED TO RESUME USE FOLLOWING ABSTINENCE. PRECLINICAL RESEARCH IN ANIMALS CONSISTENTLY DEMONSTRATES HIGHER RATES OF CONSUMPTION IN FEMALES AND THAT GONADAL SEX, CHROMOSOMAL SEX, AND ALCOHOL EXPOSURE INTERACT TO INFLUENCE LEVELS OF ALCOHOL INTAKE. IN REGARDS TO CHROMOSOMAL SEX AND ALCOHOL DRINKING BEHAVIORS, A SUBSET OF GENES OF INTEREST ON THE X CHROMOSOME ARE OF POTENTIAL INTEREST BECAUSE OF THEIR ABILITY TO ESCAPE TRANSCRIPTIONAL REPRESSION IN BRAIN TISSUES. THE CENTRAL HYPOTHESIS DRIVING THE PROPOSED STUDIES IS THAT X CHROMOSOME DOSAGE INFLUENCES ALCOHOL CONSUMPTION THROUGH OVEREXPRESSION OF THESE GENES, BUT THAT THESE EFFECTS MAY DEPEND ON GONADAL STATUS OR ALCOHOL EXPOSURE HISTORY. OUR EXPERIMENTS WILL TEST THIS HYPOTHESIS THROUGH COMPLETION OF THREE PRIMARY AIMS. WE WILL 1) DEMONSTRATE THAT ALCOHOL CONSUMPTION IS REDUCED IN MICE WITH TWO (I.E., XX) VS. ONE (I.E., XY OR XO) COPIES OF THE X CHROMOSOME, 2) DETERMINE WHETHER A HISTORY OF ALCOHOL EXPOSURE ALTERS EXPRESSION OF GENES THAT ESCAPE X CHROMOSOME INACTIVATION IN THE BRAIN AND WHETHER THESE EFFECTS DEPEND ON GONADAL STATUS, AND 3) IDENTIFY THE CANDIDATE GENE GPRASP1 AS A REGULATOR OF ALCOHOL DRINKING BEHAVIORS VIA ITS ACTIONS ON DOPAMINE RECEPTORS. THESE AIMS WILL BE ACHIEVED THROUGH THE USE OF TWO-BOTTLE CHOICE ALCOHOL DRINKING TASKS, SURGICAL GONADECTOMY, QUANTIFICATION OF GENE EXPRESSION WITH RT-PCR, SITE-SPECIFIC GENE KNOCKDOWN, AND PHARMACOLOGICAL ANTAGONISM. COLLECTIVELY, COMPLETION OF THESE AIMS WILL DEMONSTRATE A ROLE FOR THE X CHROMOSOME IN ALCOHOL CONSUMPTION AND DETERMINE WHICH X CHROMOSOME GENES THAT ESCAPE INACTIVATION IN THE BRAIN ARE REGULATED BY ALCOHOL EXPOSURE. FURTHER, WE WILL IDENTIFY GPCR REGULATION THROUGH GPRASP1 AS A MEDIATOR OF SEX DIFFERENCES IN ALCOHOL DRINKING BEHAVIORS. THESE STUDIES WILL BE THE FIRST MECHANISTIC DEMONSTRATION OF HOW SEX CHROMOSOME COMPLEMENT INFLUENCES VULNERABILITY TO ALCOHOL. ADDITIONALLY, THE PROPOSED WORK AND FUTURE RELATED STUDIES HAVE A HIGH LIKELIHOOD OF REVEALING MULTIPLE TARGETS WITH POTENTIAL THERAPEUTIC EFFICACY FOR PROBLEMATIC DRINKING BEHAVIORS IN PEOPLE OF ALL SEXES AND GENDERS.

LTREB RENEWAL: RESPONSE OF A RESERVOIR ECOSYSTEM TO CHANGING SUBSIDIES OF NUTRIENTS AND DETRITUS -THIS RESEARCH EXAMINES HOW LONG-TERM CHANGES IN AGRICULTURE AFFECT STREAMS AND LAKES, USING AN OHIO LANDSCAPE AS A MODEL SYSTEM. IN ACTON LAKE, THE AMOUNT OF ALGAE IS CONTROLLED MOSTLY BY CONCENTRATIONS OF SUSPENDED SEDIMENTS (SS) IN THE WATER (BECAUSE SS BLOCK LIGHT THAT ALGAE NEED), NUTRIENTS ENTERING FROM STREAMS, AND THE ABUNDANCE OF BOTTOM-FEEDING FISH (THESE FISH CONSUME SEDIMENTS AND EXCRETE NUTRIENTS INTO THE WATER). IN THE 1990S, THE USE OF CONSERVATION TILLAGE (REDUCED-TILLAGE AND NO-TILLAGE FARMING) INCREASED GREATLY ON FARMLAND. THIS REDUCED SOIL EROSION, AND STRONGLY AFFECTED NUTRIENTS AND SEDIMENTS IN STREAMS THAT ENTER ACTON LAKE. ALSO, THE ABUNDANCE OF BOTTOM-FEEDING FISH IN THE LAKE INCREASED. THIS PROJECT EXPLORES LONG-TERM CHANGES IN LAKE ALGAE, RELATED TO CHANGES AGRICULTURE AND THE ABUNDANCE OF SEDIMENT-FEEDING FISH. THE RESEARCH IS IMPORTANT BECAUSE SIMILAR AGRICULTURAL CHANGES ARE OCCURRING THROUGHOUT THE US, BUT LITTLE IS KNOWN ABOUT LONG-TERM EFFECTS ON STREAMS AND LAKES. THUS, THIS RESEARCH WILL HELP INFORM MANAGEMENT OF AGRICULTURE AND WATER QUALITY. THE PROJECT INCLUDES A SIGNIFICANT STUDENT TRAINING COMPONENT, AS WELL AS PUBLIC OUTREACH. THIS PROJECT EXPLORES TEMPORAL DYNAMICS IN ECOSYSTEM SUBSIDIES AND THEIR CONSEQUENCES. AFTER CONSERVATION TILLAGE INCREASED IN THE 1990S, TILLAGE WAS STABLE FOR 10-15 YEARS, BUT THEN DECREASED IN RECENT YEARS. BIOMASS OF DETRITIVOROUS FISH (GIZZARD SHAD), AND THEREFORE THEIR NUTRIENT EXCRETION, INCREASED OVER ROUGHLY THE FIRST 12 YEARS, THEN WAS STABLE UNTIL AN INCREASE IN RECENT YEARS. OVER THE FIRST DECADE, CONCENTRATIONS OF PHOSPHORUS (P) AND SS IN STREAMS DECLINED. LAKE PHYTOPLANKTON BIOMASS INCREASED GREATLY, DUE TO REDUCED LIGHT LIMITATION (BECAUSE OF DECREASED SS IN THE LAKE) AND INCREASED EXCRETION BY FISH. HOWEVER, OVER THE NEXT 10-15 YEARS, STREAM CONCENTRATIONS OF DISSOLVED P INCREASED, STREAM NITRATE AND SS DECREASED, AND LAKE PHYTOPLANKTON BIOMASS HAS BEEN RELATIVELY STABLE. DURING THIS PERIOD, PHYTOPLANKTON HAVE BECOME INCREASINGLY N-LIMITED AND LESS P-LIMITED. THE SHIFT IN NUTRIENT LIMITATION COINCIDES WITH DECREASING N:P IN STREAMS, AND INCREASED EXCRETION BY FISH, WHOSE FECAL CONTENT HAS A LOW N:P. THE PROJECT EXPLORES SEVERAL PREDICTIONS: 1) IN STREAMS, DISSOLVED P WILL CONTINUE TO INCREASE WHILE NITRATE DECLINES; 2) GIZZARD SHAD EXCRETION RATES WILL REMAIN HIGH; 3) PHYTOPLANKTON WILL BECOME MORE N-LIMITED AND LESS P-LIMITED; AND 4) PHYTOPLANKTON BIOMASS WILL BE STABLE, OR WILL DECLINE AS N BECOMES MORE LIMITING. THE PROJECT WILL PROVIDE MENTORING FOR SEVERAL UNDERGRADUATE AND GRADUATE STUDENTS WHO WILL CONDUCT RESEARCH PROJECTS, TARGETING STUDENTS FROM UNDERREPRESENTED GROUPS, AND WILL IMPLEMENT SEVERAL OUTREACH ACTIVITIES FOR THE GENERAL PUBLIC AND FARMERS. 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.

ELECTRONICS AND COMPUTING SERVICE SCHOLARS

REU SITE: SUMMER UNDERGRADUATE RESEARCH IN CHEMISTRY AND BIOCHEMISTRY AT MIAMI UNIVERSITY -THIS RESEARCH EXPERIENCES FOR UNDERGRADUATES (REU) SITE AWARD TO MIAMI UNIVERSITY, LOCATED IN OXFORD, OH, SUPPORTS THE TRAINING OF 10 STUDENTS FOR 10 WEEKS DURING THE SUMMERS OF 2024-2027. IN THIS PROGRAM, FUNDED BY THE DIVISION OF CHEMISTRY, PARTICIPANTS WILL PARTICIPATE IN WIDE-RANGING, INDEPENDENT AND COLLABORATIVE RESEARCH EXPERIENCES IN CHEMISTRY TO DEVELOP AND REFINE STUDENTS? EXPERIMENTAL SKILLS AND ENHANCE THEIR ABILITY TO WORK AS PART OF A RESEARCH TEAM. THE COMBINATION OF INTENSE RESEARCH, PROFESSIONAL DEVELOPMENT, AND COHORT BUILDING WILL PROVIDE THE NEXT GENERATION OF SCIENTISTS WITH A WELL-ROUNDED EXPERIENCE AND STRONG ENCOURAGEMENT TO CONTINUE IN ONE OF MANY AREAS OF SCIENCE AS A CAREER. THE PROJECT FOCUSES ON STUDENTS UNDERREPRESENTED IN CHEMISTRY AND/OR THOSE WHO DO NOT HAVE OPPORTUNITIES FOR RESEARCH AT THEIR HOME INSTITUTION. STUDENTS WILL CHOOSE FROM RESEARCH PROJECTS IN ANALYTICAL, BIOLOGICAL, INORGANIC, ORGANIC, AND PHYSICAL CHEMISTRY, WITH MOST PROJECTS BEING INTERDISCIPLINARY, SUCH AS BIOANALYTICAL, BIO-INORGANIC, BIOPHYSICAL, AND NANOTECHNOLOGY. STUDENTS WILL ALSO PARTICIPATE IN SESSIONS THAT WILL COVER A NUMBER OF TOPICS ASSOCIATED WITH PROFESSIONAL DEVELOPMENT INCLUDING THE DEVELOPMENT OF RESEARCH PROPOSALS, SCIENTIFIC PRESENTATIONS, ETHICS IN SCIENCE, CAREERS IN CHEMISTRY AND BIOCHEMISTRY INCLUDING SCIENCE POLICY, AND ACTIVITIES TO EXPOSE STUDENTS TO VARIOUS JOB OPPORTUNITIES AND TO BUILD A STRONG COHORT. MANY UNDERGRADUATE CHEMISTRY AND BIOCHEMISTRY STUDENTS OFTEN LACK EXPOSURE TO SCIENTIFIC RESEARCH CAREER OPPORTUNITIES OR OPPORTUNITIES TO APPLY CRITICAL THINKING SKILLS TO OPEN-ENDED RESEARCH. THIS PROJECT WILL PROVIDE THOSE OPPORTUNITIES. THE BROADER IMPACTS OF MIAMI UNIVERSITY'S CHEMISTRY AND BIOCHEMISTRY REU PROGRAM IS TO PROMOTE RESEARCH IN CHEMISTRY AND BIOCHEMISTRY AS A CAREER, ESPECIALLY FOR STUDENTS UNDERREPRESENTED IN THE PHYSICAL SCIENCES. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

MRI: ACQUISITION OF A HIGH RESOLUTION ANALYTICAL TRANSMISSION ELECTRON MICROSCOPE FOR THE MIAMI UNIVERSITY ELECTRON MICROSCOPE FACILITY

CAN OPTICAL SPECTROSCOPY PREDICT EARLY TREATMENT RESPONSE IN SOLID TUMORS

ACCESSIBLE ROUTING USING SMART CROWD-SENSED SURFACE CLASSIFICATION FOR WHEELCHAIR USERS - PEOPLE WITH AMBULATORY DISABILITIES ARE REQUIRED TO MAKE NUMEROUS CHOICES EACH DAY TO REMAIN INDEPENDENT IN THE COMMUNITY AND TO MAXIMIZE THEIR PARTICIPATION. HOWEVER, THE INFORMATION NEEDED FOR DECISION-MAKING RELATED TO BEST ROUTING AND NAVIGATION IS OFTEN ELUSIVE AND TOO GENERIC. THE MYPATH PROJECT PROPOSES TO DEVELOP A SOFTWARE SYSTEM THAT WILL RUN ON ANY SMARTPHONE TO A) COLLECT THE VIBRATION GENERATED BY DIFFERENT PATH ACROSS THE BUILT ENVIRONMENT, B) CLASSIFY PATH ACCESSIBILITY AND C) CREATE PERSONALIZED POINT-TO-POINT ROUTES WITH STEP-BY-STEP NAVIGATION INFORMATION.POPULATION AND GOAL: THE GOAL OF THIS PROJECT IS TO ENABLE PEOPLE WITH AMBULATORY DISABILITIES TO SUCCESSFULLY PARTICIPATE IN THE COMMUNITY BY FACILITATING EQUAL ACCESS TO ALL PUBLIC AREAS, SUCH AS PUBLIC BUILDINGS, PARKS, ROADS AND SIDEWALKS, AND EVEN BEACHES. THREE OBJECTIVES:1.DEVELOP A SMART APP PROTOTYPE FOR DATA COLLECTION & CLASSIFICATION OF OUTDOOR PATH ACCESSIBILITY; 2.DEVELOP A PERSONALIZED ACCESSIBLE ROUTING AND NAVIGATION FUNCTION FOR THE APP PROTOTYPE USING THE PATH ACCESSIBILITY DATA; AND 3.COMPLETE PRELIMINARY VALIDATION OF THE APP FOR FUNCTIONALITY, USABILITY, AND PSYCHOMETRICS. OUTCOMES: 1.WHEELCHAIR USERS WILL BE BETTER EQUIPPED TO FACE THE CHALLENGES OF NAVIGATING THE UNFAMILIAR SURROUNDINGS WHILE USING THE MYPATH APP, 2.THE CROWDSOURCED DATA COLLECTED THROUGH THE MYPATH APP, AVAILABLE THROUGH OPENSTREETMAP (OSM) FOR THE CITY PLANNERS AND DESIGNERS, ENGINEERS, AND OTHER STAKEHOLDERS, 3.THE TECHNIQUE OF PATH LABELLING WILL BECOME ACCEPTED METHOD OF IDENTIFYING ACCESSIBLE AND INACCESSIBLE FEATURES. PRODUCTS:1.THE MYPATH APP FOR ACCESSIBLE ROUTING AND NAVIGATION2.WHEELCHAIR USER TRAINING OF THE MYPATH APP, 3.MARKETING AND OUTREACH MATERIALS4. LIVE OUTCOMES DATABASE IN THE FORM OF OSM.

CAREER: DYNAMIC POLYMER MATERIALS WITH ADVANCED POLYMER ARCHITECTURE AND CARBON NANOTUBE REINFORCEMENTS

CONTROL OF LIPID METABOLISM AND MUSCLE HYPERTROPHY BY PPARS IN GRAY CATBIRD ANNUAL LIFE CYCLE

CAREER: THE DE NOVO DISCOVERY OF TRANSPOSABLE ELEMENTS FOR THE STUDY OF NEUTRAL SUBSTITUTION RATE VARIATION IN PLANT GENOMES

INVESTIGATING MEMBRANE PROTEINS WITH MAGNETIC RESONANCE SPECTROSCOPY -WITH THE SUPPORT OF THE CHEMISTRY OF LIFE PROCESSES PROGRAM, PROFESSOR GARY A. LORIGAN FROM THE MIAMI UNIVERSITY IS STUDYING TWO MEMBRANE PROTEINS, NAMELY PINHOLIN AND GP28, WHICH ARE INVOLVED IN CELL LYSIS/CELL DEATH. MEMBRANE PROTEINS MAKE UP APPROXIMATELY ONE-THIRD OF ALL KNOWN PROTEINS AND ARE RESPONSIBLE FOR MANY IMPORTANT PROPERTIES AND FUNCTIONS OF BIOLOGICAL SYSTEMS. DESPITE THEIR ABUNDANCE AND IMPORTANCE, THERE IS VERY LITTLE INFORMATION ABOUT MEMBRANE-ASSOCIATED MOLECULES. THIS PROJECT WILL APPLY ELECTRON PARAMAGNETIC RESONANCE (EPR) SPECTROSCOPIC TECHNIQUES TO GATHER INFORMATION ABOUT THE STRUCTURAL AND DYNAMIC PROPERTIES OF THE MEMBRANE PROTEINS PINHOLIN AND GP28. IN THE IMPLEMENTATION OF THIS PROJECT, GRADUATE STUDENTS AND UNDERGRADUATE STUDENT WILL ACQUIRE KNOWLEDGE AND EXPERIENCE IN THE PREPARATION OF MEMBRANE PROTEIN SAMPLES AND IN STATE-OF-THE-ART EPR SPECTROSCOPIC TECHNIQUES. UNDERGRADUATE STUDENTS WILL OBTAIN VALUABLE EXPERIENCE IN BIOPHYSICAL CHEMISTRY AND GRADUATE STUDENTS PARTICIPATION IN DUOS, A STEM (SCIENCE, TECHNOLOGY, ENGINEERING AND MATHEMATICS) PROJECT AT MIAMI UNIVERSITY, IS AN OPPORTUNITY FOR THEM TO BECOME OUTSTANDING MENTORS. PINHOLIN IS A BIOLOGICALLY SIGNIFICANT MEMBRANE-BOUND HOLIN PROTEIN THAT IS DIRECTLY INVOLVED IN CELL DEATH THROUGH LYSIS OF THE INNER MEMBRANE IN E. COLI. THE OTHER PRINICIPAL TARGET OF THESE STUDIES IS GP28, A NEW TYPE OF PROTEIN THAT DISRUPTS THE OUTER MEMBRANE (OM) IN PHAGE PHIKT. CURRENTLY, THERE IS VERY LIMITED STRUCTURAL INFORMATION ON BOTH PINHOLIN AND GP28. THE SECONDARY AND TERTIARY STRUCTURE OF MUTATED PINHOLIN EMBEDDED IN A LIPID BILAYER WILL BE ELUCIDATED BY MEASURING DISTANCES BETWEEN STRATEGICALLY PLACED NITROXIDE SPIN LABELS USING EPR SPECTROSCOPY. STATE-OF-THE-ART EPR TECHNIQUES SUCH AS DOUBLE ELECTRON ELECTRON RESONANCE (DEER) WILL BE APPLIED TO STUDY THE STRUCTURE, TOPOLOGY, OLIGOMERIZATION STATE, AND DYNAMIC PROPERTIES OF THE MEMBRANE-BOUND PROTEINS PINHOLIN AND GP28. DIFFERENT CONFORMATIONAL FORMS WILL BE INVESTIGATED. THE EPR DATA WILL BE USED IN THE DEVELOPMENT OF A STRUCTURAL MODEL TO HELP ELUCIDATE THE MECHANISM OF HOLE FORMATION. 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.

EFFECTS OF APOLIPOPROTEIN A4 ON LIPID METABOLISM VIA SYMPATHETIC REGULATION - OBESITY INCREASES THE RISKS AND PROGRESSION OF HYPERTRIGLYCERIDEMIA, METABOLIC DYSFUNCTION- ASSOCIATED STEATOTIC LIVER DISEASE (MASLD), AND CARDIOVASCULAR DISEASES. PREVIOUS STUDIES DEMONSTRATE THAT A SINGLE INJECTION OF APOLIPOPROTEIN A4 (APOA4) ELEVATES SYMPATHETIC NEURAL ACTIVITY AND FATTY ACID Β-OXIDATION IN ADIPOSE TISSUES; AND CONSISTENT INFUSION OF APOA4 IN OBESE MICE FED A HIGH-FAT DIET LOWERS FAT MASS, REDUCES HYPERTRIGLYCERIDEMIA, ELEVATES BROWN ADIPOSE TISSUE THERMOGENESIS, AND ATTENUATES STEATOSIS AND ENHANCES SYMPATHETIC NEURAL ACTIVITY IN THE LIVER. THIS PROJECT HYPOTHESIZES THAT APOA4 REDUCES HYPERTRIGLYCERIDEMIA BY REGULATING LIPID METABOLISM THROUGH SYMPATHETIC STIMULATION IN ADIPOSE TISSUES (SPECIFIC AIM 1) AND SYMPATHETIC ACTION IN THE LIVER (SPECIFIC AIM 2). THE ROLE OF SYMPATHETIC ACTION VIA THE NEUROTRANSMITTER NOREPINEPHRINE AND ADRENERGIC RECEPTOR-MEDIATED PATHWAYS WILL BE INVESTIGATED, AND THEIR NECESSITY IN APOA4-MEDIATED LIPID METABOLISM WILL BE TESTED. A STRENGTH OF THIS PROJECT IS THE INTERDISCIPLINARY COLLABORATION BETWEEN INVESTIGATORS WITH ESTABLISHED SUCCESSFUL COLLABORATION AND PUBLICATIONS. THE PROJECT WILL PROVIDE PHYSIOLOGICAL, MOLECULAR, AND NEUROCHEMICAL MECHANISMS UNDERLYING HOW APOA4 DIFFERENTIALLY REGULATES METABOLISM THROUGH SYMPATHETIC ACTIVATION IN VARIOUS TYPES OF ADIPOSE TISSUES AND THE LIVER IN MALE AND FEMALE OBESE MICE. FINDINGS WOULD PROVIDE IMPETUS TO DEVELOP UNIQUE, NOVEL, TARGETED THERAPEUTIC APPLICATIONS AGAINST HYPERTRIGLYCERIDEMIA AND MASLD. IMPORTANTLY, THIS PROJECT WILL EXPOSE UNDERGRADUATES AND GRADUATE STUDENTS TO MERITORIOUS RESEARCH, PROVIDE STUDENTS WITH HANDS-ON BIOMEDICAL RESEARCH EXPERIENCE, AND STRENGTHEN RESEARCH ENVIRONMENT AT R15 ELIGIBLE INSTITUTIONS.

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

PROBING SUBSTRATE/INHIBITOR BINDING TO METALLOENZYMES USING EPR

LOBES OR GILLS, EXPLORING THE ORIGIN OF INSECT WINGS

CAREER: RATIONALE CAPTURE FOR HIGH-ASSURANCE SYSTEMS

POLYMER-LIPID PARTICLES INVESTIGATED BY MAGNETIC RESONANCE SPECTROSCOPY - PROJECT SUMMARY/ABSTRACT MEMBRANE PROTEINS REPRESENT APPROXIMATELY 30% OF ALL KNOWN PROTEINS BUT ONLY APPROXIMATELY 1% OF ALL SOLVED PROTEIN STRUCTURES. DESPITE RECENT ADVANCES IN METHODS FOR MEMBRANE PROTEIN STRUCTURAL BIOLOGY, KNOWLEDGE ABOUT THIS IMPORTANT CLASS OF PROTEINS LAGS BEHIND THEIR SOLUBLE COUNTERPARTS. MEMBRANE PROTEINS ARE CRITICAL TO NUMEROUS ASPECTS OF HEALTH, RANGING FROM REGULATION CELLULAR FUNCTION AND TRANSPORT INTO AND OUT OF THE CELL, THROUGH TO VIRAL INFECTIONS WHICH USE MEMBRANE PROTEINS AS PART OF THE INFECTION CYCLE. UNDERSTANDING THE STRUCTURE OF MEMBRANE PROTEINS CAN BE CRITICAL TO DISRUPTING SUCH VIRAL INFECTIONS, AND CAN ALSO LEAD TO THE DEVELOPMENT OF EFFECTIVE ANTIVIRAL THERAPIES. IN ALMOST 90% OF NEWLY DEVELOPED AND APPROVED THERAPEUTICS, PROTEIN STRUCTURAL INFORMATION WAS USED TO GUIDE THE DEVELOPMENT OF THE THERAPEUTIC MOLECULES. DUE TO THE LIMITED AND INCOMPLETE STRUCTURAL INFORMATION ON MEMBRANE BOUND PROTEINS, THE DEVELOPMENT OF THERAPEUTICS AND TREATMENTS THAT TARGET MEMBRANE BOUND PROTEINS IS LIMITED. A SIGNIFICANT CONTRIBUTION TO THE CHALLENGES IN ELUCIDATING MEMBRANE PROTEIN STRUCTURES IS THE LACK OF ROBUST AND APPROPRIATE LIPID MEMBRANE MIMETICS. EXISTING MEMBRANE MIMETICS INTRODUCE NOTABLE CHALLENGES THAT LIMIT MEMBRANE PROTEIN STRUCTURAL DETERMINATION. THESE CHALLENGES RANGE FROM HIGHLY CURVED MICELLES WHICH MAY NOT REPRESENT THE ESSENTIALLY FLAT LIPID BILAYER, LACK OF COMPATIBILITY WITH MANY LIPIDS FOR BICELLES, LARGE SIZES OF VESICLES WHICH INTRODUCES ANISOTROPY, COST AND POTENTIAL BACKGROUND SIGNAL FROM MEMBRANE SCAFFOLD PROTEINS, AND LACK OF CONTROL OVER POLYMER STRUCTURE AND THE PRESENCE OF AROMATIC GROUPS ON SEVERAL EXISTING NANODISC FORMING POLYMERS. THIS HIGHLIGHTS AN URGENT NEED TO DEVELOP LIPID MEMBRANE MIMETICS WHICH BOTH PROVIDE A GOOD APPROXIMATION TO THE NATIVE LIPID BILAYER IN TERMS OF BOTH STRUCTURE AND CURVATURE, WHILE ALSO FACILITATING STRUCTURAL ANALYSIS OF THE MEMBRANE PROTEIN EMBEDDED IN THE MIMETIC. YET POLYMER STRUCTURE-FUNCTION RELATIONSHIPS ARE NOT WELL ESTABLISHED FOR POLYMERS THAT INTERACT WITH LIPIDS AND MEMBRANE PROTEINS. THIS PROJECT WILL USE MODERN CONTROLLED POLYMER CHEMISTRY TOOLS, TO CREATE A NEW CLASS OF POLYMERS THAT WILL SELF-ASSEMBLE WITH LIPIDS. THESE SELF ASSEMBLED POLYMER-LIPID SYSTEMS WILL FORM WELL DEFINED DISCS ON THE ORDER OF 10S OF NANOMETERS, GIVING LIPID MEMBRANE MIMETICS SUITABLE FOR THE ANALYSIS OF MANY MEMBRANE PROTEINS. THE ADVANCED POLYMER CHEMISTRY TECHNIQUES WILL ENABLE FINE TUNING OF POLYMER’S LENGTH, CHARGES, AND HYDROPHOBICITY. POLYMERS WILL ALSO BE MODIFIED WITH SPIN-LABELS FOR ELECTRON PARAMAGNETIC RESONANCE SPECTROSCOPY, A MAGNETIC RESONANCE METHOD. THE MAGNETIC RESONANCE SPECTROSCOPIC METHODS WILL BE USED ON POLYMERS, LIPIDS AND MEMBRANE PROTEINS MODIFIED WITH APPROPRIATE SPIN LABELS, PROVIDING INSIGHTS INTO THE LOCAL DYNAMICS AND PROXIMITIES OF THE SELF ASSEMBLED POLYMER-LIPID AND POLYMER-LIPID-MEMBRANE PROTEIN COMPLEXES. THE INFORMATION REGARDING THE STRUCTURE AND DYNAMICS OF THE SELF-ASSEMBLED COMPLEXES ACROSS THE DIVERSE RANGE OF POLYMER FUNCTIONALITY AND STRUCTURES USED WILL GIVE IMPORTANT INSIGHTS INTO HOW POLYMER STRUCTURE IMPACTS ITS INTERACTIONS AND ASSEMBLY WITH BIOLOGICAL MOLECULES. THESE INSIGHTS CAN BE USED TO GUIDE THE DESIGN OF POLYMERS FOR ROBUST LIPID MEMBRANE MIMETICS. TRAINING AND MENTORING OF UNDERGRADUATE STUDENTS AS WELL AS A GRADUATE ASSISTANT WILL BE A CORE FEATURE OF THE PROPOSED PROJECT. A DIVERSE TEAM OF STUDENTS WILL WORK ON ALL ASPECTS OF THE PROJECT, GAINING SKILLS FROM THE FUNDAMENTAL POLYMER CHEMISTRY, MAGNETIC RESONANCE SPECTROSCOPY TO MEMBRANE PROTEIN BIOPHYSICS. UNDERGRADUATE STUDENTS WILL BE INTEGRATED FULLY INTO THE PROJECTS, ALONG WITH THE GRADUATE STUDENT, GAINING SKILLS IN THIS FIELD AT THE INTERFACE OF MATERIALS SCIENCE AND BIOPHYSICS. BEYOND CORE SCIENTIFIC TRAINING, STUDENTS WILL GAIN WRITTEN AND ORAL COM

LTREB RENEWAL: RESPONSE OF A RESERVOIR ECOSYSTEM TO DECLINING SUBSIDIES OF NUTRIENTS AND DETRITUS

CAREER: IMPLEMENTING INQUIRY-BASED APPROACHES IN GEOSCIENCE EDUCATION AND RESEARCH

COLLABORATIVE RESEARCH: EXPLORING THE GENERALITY OF LIGHT NUTRIENT AND PREDATOR CONSTRAINTS ON FOOD CHAIN EFFICIENCY

A NEW HUMANITIES HUB AT MIAMI UNIVERSITY [MIAMI UNIVERSITY SEEKS A $1 MILLION NEH CHALLENGE GRANT TO CREATE A STATE-OF-THE-ART HUMANITIES CENTER IN A NEW CAMPUS HUMANITIES HUB. THE CROWN JEWEL IN A $62 MILLION RENOVATION OF BACHELOR HALL, THE NEW CENTER WILL REFLECT MIAMI UNIVERSITY'S LONG-STANDING COMMITMENT TO THE LIBERAL ARTS AND WILL PROVIDE MUCH-NEEDED SPACE FOR A CENTER THAT IS ALREADY AN ESSENTIAL SOURCE OF INTELLECTUAL INQUIRY AND ENGAGEMENT. THE RENOVATED BACHELOR HALL WILL BE A NEW HOME FOR MIAMI'S NOW FAR-FLUNG HUMANITIES DEPARTMENTS. IT WILL ANCHOR A NEW HUMANITIES AND HONORS CORRIDOR AT THE CENTER OF MIAMI'S MAIN CAMPUS. AN NEH CHALLENGE GRANT WILL SUPPORT THE ENCLOSURE OF A NOW UNUSED COURTYARD TO CREATE NEW SEMINAR ROOMS, HUMANITIES CENTER STAFF OFFICES, AND A LARGE EVENT SPACE. WHEN COMPLETE IN 2026, THE NEW CENTER WILL ENJOY PRIDE OF PLACE IN THE DYNAMIC ATRIUM AT THE HEART OF THE BUILDING, GIVING THE HUMANITIES A PROMINENT PHYSICAL PRESENCE IN A HEAVILY TRAFFICKED CAMPUS LOCATION WITH EASY PUBLIC ACCESS.]

CC* CAMPUS COMPUTE: INTERDISCIPLINARY GPU-ENABLED COMPUTE -THE TALON GRAPHICS PROCESSING UNIT (GPU) CLUSTER REPRESENTS A MAJOR LEAP FORWARD IN GPU-ACCELERATED COMPUTING AT MIAMI UNIVERSITY. WORKFORCE DEVELOPMENT AND EDUCATION EFFORTS UTILIZING THE TALON GPU CLUSTER ARE STRENGTHENING ARTIFICIAL INTELLIGENCE LITERACY AND INCORPORATING ARTIFICIAL INTELLIGENCE INTO THE HIGHER EDUCATION LANDSCAPE IN A MANNER CONSISTENT WITH BEST EDUCATIONAL PRACTICES. THESE EFFORTS ARE TRAINING AN ENGAGED COMMUNITY PREPARED TO MEET THE NEEDS OF THE U.S. ECONOMY IN MACHINE LEARNING AND ARTIFICIAL INTELLIGENCE. THE PROJECT IS LEVERAGING TALON GPU CLUSTER CAPABILITIES BY PROVIDING ACCESS THROUGH THE OPEN SCIENCE GRID, ENABLING 20% OF CLUSTER UPTIME FOR RESEARCH FROM THE BROADER COMMUNITY. THE TALON GPU CLUSTER IS A DEDICATED HIGH-PERFORMANCE COMPUTING CLUSTER COMPRISING MULTIPLE NODES, EACH WITH MULTIPLE STATE-OF-THE-ART GPUS. RESOURCE-INTENSIVE GPU-ACCELERATED COMPUTING EFFORTS ARE FACILITATED BY ONBOARD MEMORY FOR EACH GPU AND HIGH-CAPACITY ON-NODE DISK SPACE. PARALLEL COMPUTING JOB PERFORMANCE IS ENHANCED BY FAST INTERCONNECTS. RESEARCH ENABLED BY THE TALON GPU CLUSTER SPANS ALL ACADEMIC DIVISIONS AT MIAMI UNIVERSITY AND INCLUDES THE DEVELOPMENT OF SOPHISTICATED SIMULATIONS OF ATOMIC NUCLEI, THE DEVELOPMENT AND USE OF AI CHATBOTS FOR COMPLEX TECHNICAL HANDBOOKS, IN SILICO SCREENING OF ENZYME INHIBITOR CANDIDATES VIA MACHINE LEARNING, AND THE DEVELOPMENT OF MACHINE LEARNING ALGORITHMS FOR AUTOMATED ANALYSIS OF IMAGE-BASED MANUFACTURING QUALITY CONTROL. THE INTERDISCIPLINARY AND COLLABORATIVE EFFORTS OF MIAMI UNIVERSITY RESEARCHERS AND EDUCATORS ARE INCORPORATING THE SOCIETAL AND PEDAGOGICAL IMPACT OF ARTIFICIAL INTELLIGENCE INTO COURSES AND FURTHER CONNECT THE RESEARCH TO EDUCATION EFFORTS CENTERED ON ETHICAL ISSUES AROUND ARTIFICIAL INTELLIGENCE. 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.

RESEARCH EXPERIENCES FOR UNDERGRADUATES SITE: ECOLOGY IN HUMAN-DOMINATED LANSCAPES

LTREB: RESPONSE OF A RESERVOIR ECOSYSTEM TO DECLINING SUBSIDIES OF NUTRIENTS AND DETRITUS

CAREER: DYNAMIC REGULATION OF PROTEIN QUALITY CONTROL

ORTHO-PHENYLENE OLIGOMERS AND GRAPHENE NANORIBBONS

GSE/RES: STAYING IN STEM: EXAMINING COMMUNAL GOAL CONGRUITY PROCESSES IN THE RETENTION OF WOMEN

THYLAKOID ASSEMBLY AND FOLDED PROTEIN TRANSPORT BY THE CHLOROPLAST TWIN ARGININE TRANSLOCATION (CPTAT) PATHWAY

SHORT- AND LONG-RANGE STRUCTURAL COMPLEXITY FROM ORTHO-ARYLENE FOLDAMERS -WITH THE SUPPORT OF THE MACROMOLECULAR, SUPRAMOLECULAR AND NANOCHEMISTRY PROGRAM IN THE DIVISION OF CHEMISTRY, PROFESSOR C. SCOTT HARTLEY OF MIAMI UNIVERSITY WILL INVESTIGATE METHODS BY WHICH THE FOLDING OF NON-BIOLOGICAL MOLECULES CAN BE CONTROLLED. BIOCHEMICAL SYSTEMS MAKE USE OF MOLECULES THAT ARE BOTH LARGE AND STRUCTURALLY COMPLEX. THIS COMBINATION IS NECESSARY FOR THE REMARKABLE SOPHISTICATION, AND THUS FUNCTION, OF BIOCHEMICAL SYSTEMS. CONSTRUCTING COMPARABLE NON-BIOLOGICAL MOLECULES IS CURRENTLY BEYOND THE CAPABILITIES OF SYNTHETIC CHEMISTRY. NATURE?S STRATEGY FOR GENERATING STRUCTURAL COMPLEXITY IS BY FOLDING A LONG CHAIN MOLECULE INTO A SPECIFIC SHAPE. THIS RESEARCH PROJECT AIMS TO INCREASE OUR UNDERSTANDING OF THE FACTORS THAT GOVERN THE FOLDING OF LONG CHAIN MOLECULES. THE ABILITY TO CONTROL MOLECULAR FOLDING INTO COMPLEX 3D STRUCTURES IS IMPORTANT FOR ADVANCED APPLICATIONS IN MOLECULAR RECOGNITION AND CATALYSIS. THE WORK WILL INVOLVE GRADUATE STUDENTS AND UNDERGRADUATES, WHO WILL BE TRAINED IN SYNTHETIC AND PHYSICAL ORGANIC CHEMISTRY. ADDITIONAL BROADER IMPACTS INCLUDE THE DEVELOPMENT OF A NEW TEACHING LABORATORY ACTIVITY ON ATTRACTIVE INTERACTIONS RELEVANT TO MOLECULAR FOLDING AND WORK WITH A PROGRAM FROM A CONSORTIUM OF OHIO UNIVERSITIES SUPPORTING STUDENTS FROM UNDERREPRESENTED BACKGROUNDS. THIS PROJECT AIMS TO STUDY THE FOLDING OF A CLASS OF NON-BIOLOGICAL MOLECULES CALLED ?FOLDAMERS? AND TO DEVELOP TWO STRATEGIES FOR CONTROLLING THEIR FOLDING INTO 3D STRUCTURES. MORE SPECIFICALLY, THIS PROJECT WILL FOCUS ON STUDYING ORTHO-ARYLENE FOLDAMERS. ORTHO-PHENYLENES ARE A SIMPLE CLASS OF AROMATIC FOLDAMERS THAT EXHIBIT TWO VERY USEFUL PROPERTIES: THEIR FOLDED STRUCTURES CAN BE DETERMINED IN SOLUTION WITH GREAT PRECISION USING NUCLEAR MAGNETIC RESONANCE (NMR) SPECTROSCOPY AND COMPUTATIONAL CHEMISTRY, AND THEIR FOLDING PROPENSITIES ARE WEAK ENOUGH TO BE EASILY PERTURBED. THESE PROPERTIES MAKE THEM WELL SUITED TO PROGRESSING FROM SECONDARY TO TERTIARY STRUCTURE, A CURRENT CHALLENGE FOR FOLDAMERS RESEARCH. IN THE FIRST STRATEGY, THE FOLDING OF CHAINS THAT MIX ATTRACTIVE AND REPULSIVE INTERACTIONS WITHIN A SINGLE MOLECULE WILL BE STUDIED. BY PROGRAMMING FOLDING THROUGH THE INCORPORATION OF PYRAZINE-2,3-DIYL UNITS INTO THE SEQUENCE, COMPLEX STRUCTURES WILL BE OBTAINED THAT ARE TO BE USED TO CONSTRUCT THE COIL SEGMENTS NECESSARY FOR TERTIARY STRUCTURE. IN THE SECOND STRATEGY, CAGE STRUCTURES INCORPORATING MULTIPLE O-PHENYLENE UNITS WILL BE INVESTIGATED AS SIMPLE EXAMPLES OF TERTIARY STRUCTURE. EMPHASIS WILL BE PLACED ON UNDERSTANDING HOW THE FOLDING OF THE O-PHENYLENES RESPONDS TO CAGE GEOMETRY AND THE INCLUSION OF GUEST MOLECULES. THIS RESEARCH HAS THE POTENTIAL TO PROVIDE ACCESS TO AND UNDERSTANDING OF FUNDAMENTALLY NEW MOLECULAR FOLDER SYSTEMS TO BUILD COMPLEX NON-BIOLOGICAL STRUCTURES WITH GREAT POTENTIAL FOR BINDING SMALL MOLECULE ANALYTES AND THE POTENTIAL FOR PROVIDING A NEW MOLECULAR SCAFFOLD FOR CATALYSIS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

ECA/A/E/USS ACADEMIC EXCHANGE PROGRAMS: STUDY OF THE US PROGRAMS PROJECT: GLOBAL

DEVELOPMENT OF A NOVEL HUMAN MATERIALS HYPERSPECTRAL REMOTE SENSING TOOL FOR FORENSIC INVESTIGATIONS AND OPERATIONS FOR U.S. LAW ENFORCEMENT

ABI INNOVATION: ANALYSIS OF OPERON EVOLUTION USING AN EVEN DRIVEN APPROACH

CONFIGURAL FACE PROCESSING AND PREJUDICE REGULATION

REU SITE: ECOLOGY IN HUMAN-DOMINATED LANDSCAPES -THIS REU SITE AWARD TO MIAMI UNIVERSITY, LOCATED IN OXFORD, OH, WILL SUPPORT THE TRAINING OF 12 STUDENTS FOR 10 WEEKS DURING THE SUMMERS OF 2022- 2024. IT IS ANTICIPATED THAT A TOTAL OF 36 STUDENTS, PRIMARILY FROM SCHOOLS WITH LIMITED RESEARCH OPPORTUNITIES OR FROM AN UNDER-REPRESENTED GROUP, WILL BE TRAINED IN THE PROGRAM. STUDENTS WILL LEARN HOW RESEARCH IN ECOLOGY, EVOLUTION, AND ENVIRONMENTAL SCIENCE IS CONDUCTED IN LANDSCAPES ALTERED BY HUMAN ACTIVITY, AND MANY WILL PRESENT THE RESULTS OF THEIR WORK AT SCIENTIFIC CONFERENCES AND PUBLISH RESULTS IN PEER-REVIEWED SCIENTIFIC JOURNALS. STUDENTS WILL BE EQUIPPED TO GENERATE CREATIVE AND INTEGRATIVE APPROACHES TOWARD UNDERSTANDING GLOBAL ENVIRONMENTAL ISSUES, WHILE ALSO ENGAGING IN SERVICE THAT ENHANCES ENVIRONMENTAL QUALITY IN THEIR LOCAL COMMUNITIES. ASSESSMENT OF THE PROGRAM WILL BE DONE THROUGH THE USE OF ONLINE SURVEYS. STUDENTS, A SIGNIFICANT PROPORTION OF WHOM WILL PURSUE GRADUATE TRAINING IN ECOLOGY AND ENVIRONMENTAL SCIENCE OR WILL ENTER THE ENVIRONMENTAL SCIENCE WORKFORCE, WILL BE TRACKED AFTER THE PROGRAM TO DETERMINE THEIR CAREER PATHS. THIS PROGRAM WILL CREATE COLLABORATIVE CLUSTERS OF STUDENT-MENTOR PAIRS ADDRESSING ENVIRONMENTALLY RELEVANT RESEARCH QUESTIONS RELATED TO URBAN-TO-RURAL GRADIENTS, POPULATION CONNECTIVITY, AND ECOSYSTEM SERVICES. STUDENTS WILL BE EMPOWERED TO CONDUCT THEIR OWN RESEARCH PROJECTS, TO INTEGRATE THEIR RESEARCH WITH THE WORK OF OTHERS, AND TO CONSIDER THE LARGER IMPLICATIONS OF HUMAN DOMINATION OF LANDSCAPES AND THE ROLE OF SCIENCE IN SOLVING ENVIRONMENTAL PROBLEMS. ENRICHMENT ACTIVITIES WILL FOCUS ON PROFESSIONAL DEVELOPMENT; ENVIRONMENTAL ETHICS AND RESPONSIBLE CONDUCT OF RESEARCH; SERVICE TO THE COMMUNITY, AND INTERACTIONS WITH DIVERSE SCIENTISTS FROM OTHER INSTITUTIONS. STUDENT APPLICATIONS ARE ACCEPTED FROM DECEMBER-MARCH AND A DIVERSE COHORT OF PARTICIPANTS WILL BE SELECTED BASED ON THEIR ACADEMIC RECORD AND INTERESTS IN ECOLOGY, EVOLUTION, AND ENVIRONMENTAL SCIENCE PROCESS. EXAMPLE RESEARCH PROJECTS CAN BE VIEWED AT THE PROGRAM WEBSITE. MORE INFORMATION ABOUT THE PROGRAM IS AVAILABLE BY VISITING HTTP://WWW.MIAMIOH.EDU/ECOREU, OR BY CONTACTING THE PI (DR. DAVID J. BERG AT BERGDJ@MIAMIOH.EDU) OR THE CO-PI (DR. MICHELLE D. BOONE AT BOONEMD@MIAMIOH.EDU). 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.

HEALTHRICH: HEALTH RISKS, INFORMATION, AND CHOICES, PHASE II

DYNAMIC CONTROL AND SELF-ASSEMBLY OF ORTHO-PHENYLENE FOLDAMERS

NSF CAREER: ENAMINE-METAL LEWIS ACID BIFUNCTIONAL CATALYSTS FOR ASYMMETRIC ORGANIC TRANSFORMATIONS

FOXE3 IN CREATING LENS CHROMATIN ARCHITECTURE AND TRANSCRIPTIONAL IDENTITY - THE OCULAR LENS SERVES AS AN EXCELLENT MODEL FOR STUDYING CELL FATE DETERMINATION, AS IT CONSISTS OF TWO DISTINCT CELL TYPES DERIVED FROM THE SURFACE ECTODERM: LENS EPITHELIAL AND FIBER CELLS. LENS DEVELOPMENT REQUIRES SUPPRESSION OF PRO-NEUROGENIC PATHWAYS, DISTINGUISHING IT FROM OTHER ANTERIOR PLACODES, SUCH AS THE OLFACTORY PLACODE, WHICH GIVES RISE TO NEURONS. MUTATIONS IN KEY TRANSCRIPTION FACTORS (TFS), INCLUDING AP-2Α, FOXE3, AND PAX6, LEAD TO OVERLAPPING DEVELOPMENTAL DEFECTS SUCH AS APHAKIA, INCOMPLETE LENS SEPARATION, AND FIBER CELL ABNORMALITIES, SUGGESTING SHARED TRANSCRIPTIONAL TARGETS AND REGULATORY MECHANISMS. HOWEVER, A MAJOR GAP REMAINS IN UNDERSTANDING HOW FOXE3 FUNCTIONS AS A TRANSCRIPTIONAL REGULATOR AND HOW ITS ACTIVITY INFLUENCES CHROMATIN ARCHITECTURE TO SUPPRESS PRO-NEUROGENIC GENE EXPRESSION DURING LENS FORMATION. PRELIMINARY STUDIES USING CUT&RUN IDENTIFIED A DE NOVO FOXE3-BINDING MOTIF, WITH STRONG SIMILARITY TO FOXD3, AND REVEALED THAT FOXE3 IS REQUIRED TO REPRESS NEUROGENIC GENE EXPRESSION IN EARLY LENS CELLS. ADDITIONALLY, RNA-SEQ ANALYSES OF FOXE3 MUTANT LENSES DEMONSTRATED SIGNIFICANT DIFFERENTIAL GENE EXPRESSION LINKED TO PRO-NEUROGENIC PATHWAYS. THIS LED TO THE HYPOTHESIS THAT FOXE3 FUNCTIONS AS BOTH A TRANSCRIPTIONAL ACTIVATOR AND REPRESSOR, COORDINATING CHROMATIN REMODELING TO ESTABLISH AND MAINTAIN LENS CELL IDENTITY. TO TEST THIS, STATE-OF-THE-ART CHROMATIN AND TRANSCRIPTOMIC TECHNOLOGIES, INCLUDING SINGLE- NUCLEUS MULTIOMICS (ATAC-SEQ + RNA-SEQ), CUT&RUN, AND FUNCTIONAL ASSAYS IN CHICK EMBRYOS, TO DISSECT FOXE3’S MOLECULAR MECHANISMS WILL BE CONDUCTED. AIM 1 WILL IDENTIFY FOXE3 TRANSCRIPTIONAL TARGETS AND DETERMINE HOW CHROMATIN ACCESSIBILITY (DARS) AND FOXE3-BOUND ENHANCERS AND PROMOTERS ARE ALTERED IN FOXE3 MUTANT LENSES. THIS WILL BE ACCOMPLISHED THROUGH THE INTEGRATION OF SINGLE-NUCLEUS MULTIOMICS AND CUT&RUN DATA TO MAP THE FOXE3-DEPENDENT REGULATORY LANDSCAPE. AIM 2 WILL DETERMINE THE FUNCTIONAL ROLE OF FOXE3 IN CELL FATE DECISIONS BY (1) GAIN AND LOSS OF FUNCTION ASSAYS IN CHICK LENS CELLS, (2) TESTING ITS ABILITY TO SUPPRESS NEUROGENESIS IN THE DEVELOPING CHICK RETINA, AND (3) IDENTIFYING FOXE3-INTERACTING PROTEINS VIA IMMUNOPRECIPITATION AND MASS SPECTROMETRY. THE COMPLETION OF THESE AIMS WILL PROVIDE MECHANISTIC INSIGHTS INTO FOXE3’S ROLE IN LENS DEVELOPMENT, ESTABLISH A FOXE3 DNA-BINDING MOTIF, AND IDENTIFY TARGETS OF FOXE3 REGULATION. THESE STUDIES AIM TO REVEAL HOW FOXE3 MUTATIONS CONTRIBUTE TO CONGENITAL EYE DISORDERS SUCH AS APHAKIA, CATARACTS, MICROPHTHALMIA, COLOBOMA, AND PETERS ANOMALY. BY ELUCIDATING THE CHROMATIN REGULATORY MECHANISMS UNDERLYING LENS CELL IDENTITY, THIS WORK HAS THE POTENTIAL TO INFORM THERAPEUTIC STRATEGIES FOR HUMAN EYE DISEASES LINKED TO TRANSCRIPTIONAL DYSREGULATION.

STRATEGIES TO ACCOMMODATE READING IN APHASIA: USING ASSISTIVE TECHNOLOGY TO SUPPORT READING BY PEOPLE WITH APHASIA

REU SITE: ECOLOGY IN HUMAN-DOMINATED LANDSCAPES -THIS REU SITE AWARD TO MIAMI UNIVERSITY, LOCATED IN OXFORD, OH, WILL SUPPORT THE TRAINING OF 10 STUDENTS FOR 10 WEEKS DURING THE SUMMERS OF 2025?2027. IT IS ANTICIPATED THAT A TOTAL OF 30 STUDENTS WILL PARTICIPATE, PRIMARILY FROM SCHOOLS WITH LIMITED RESEARCH OPPORTUNITIES. STUDENTS WILL BE EQUIPPED TO GENERATE CREATIVE AND INTEGRATIVE APPROACHES TOWARD UNDERSTANDING GLOBAL ENVIRONMENTAL ISSUES THROUGH DATA-DRIVEN INDIVIDUAL RESEARCH PROJECTS. THEY WILL EXPLORE THE WAYS IN WHICH HUMAN POPULATIONS SHAPE THE LAND OVER TIME AND THE WAYS IN WHICH HUMANS SOLVE ENVIRONMENTAL PROBLEMS SUCH AS POLLUTION, LOSS OF BIODIVERSITY, AND SOIL DEGRADATION. STUDENTS WILL LEARN HOW RESEARCH IN ECOLOGY, EVOLUTION, AND ENVIRONMENTAL SCIENCE IS CONDUCTED, AND MANY WILL PRESENT THE RESULTS OF THEIR WORK AT SCIENTIFIC CONFERENCES AND PUBLISH RESULTS IN PEER-REVIEWED SCIENTIFIC JOURNALS. A SIGNIFICANT PROPORTION OF THE STUDENTS WILL PURSUE GRADUATE TRAINING AND/OR HAVE CAREERS IN ECOLOGY AND ENVIRONMENTAL SCIENCE, THUS STRENGTHENING THE SCIENTIFIC WORKFORCE. MORE INFORMATION ABOUT THE PROGRAM IS AVAILABLE BY VISITING HTTPS://SITES.MIAMIOH.EDU/ECOLOGYREU/. STUDENTS SHOULD APPLY TO THIS REU SITE USING NSF ETAP (EDUCATION AND TRAINING APPLICATION: HTTPS://ETAP.NSF.GOV). THIS PROGRAM CREATES COLLABORATIVE CLUSTERS OF STUDENT-MENTOR PAIRS ADDRESSING ENVIRONMENTALLY RELEVANT RESEARCH QUESTIONS RELATED TO COUPLED HUMAN-NATURAL SYSTEMS, SPATIAL PATTERN & CONNECTIVITY, AND SPECIES INTERACTIONS. STUDENTS WILL CONDUCT INDIVIDUAL RESEARCH PROJECTS THAT INTEGRATE INTO A LARGER ECOLOGICAL THEME AND WILL CONSIDER THE IMPLICATIONS OF HUMAN SHAPING OF LANDSCAPES AND THE ROLE OF SCIENCE IN THE CREATION OF SOLUTIONS TO ENVIRONMENTAL CHALLENGES. FACULTY MENTORS WILL BE DRAWN FROM MIAMI?S DEPARTMENTS OF BIOLOGY, GEOGRAPHY, GEOLOGY & ENVIRONMENTAL EARTH SCIENCES, AND MICROBIOLOGY. ENRICHMENT ACTIVITIES WILL FOCUS ON PROFESSIONAL DEVELOPMENT AND RESPONSIBLE CONDUCT OF RESEARCH; AND INTERACTIONS WITH SCIENTISTS FROM OTHER INSTITUTIONS. PARTICIPANTS WILL BE TRACKED AFTER THE PROGRAM TO DETERMINE THEIR CAREER PATHS. EXAMPLE RESEARCH PROJECTS CAN BE VIEWED AT THE PROGRAM WEBSITE. IN ADDITION TO TRAINING IN SCIENTIFIC RESEARCH, REU STUDENTS WILL BUILD ON THEIR KNOWLEDGE OF ENVIRONMENTAL ETHICS AND HOW IT CAN ALTER THE LAND AND ITS INHABITANTS. SUCH PERSPECTIVES ARE CRITICAL FOR DEVELOPING CREATIVE, INTEGRATIVE, AND WISE APPROACHES IN SCIENCE, MANAGEMENT, AND POLICY. THROUGH RESEARCH, SITE VISITS, READINGS, AND DISCUSSIONS, OUR PARTICIPANTS WILL BE PREPARED TO TACKLE EMERGING GLOBAL CHALLENGES. 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.

CPATH-2: COLLABORATIVE RESEARCH: INCORPORATING COMMUNICATION OUTCOMES INTO THE COMPUTER SCIENCE CURRICULUM

MOLECULAR MECHANISMS CONTRIBUTING EVOLUTIONARY MORPHOLOGICAL DIVERSITY

CAS: RESPONSIVE MACROMOLECULES BY WAVELENGTH CONTROLLED VINYL KETONE PHOTOPOLYMERIZATION AND PHOTODEGRADATION -WITH THE SUPPORT OF THE MACROMOLECULAR, SUPRAMOLECULAR AND NANOCHEMISTRY PROGRAM IN THE DIVISION OF CHEMISTRY, DOMINIK KONKOLEWICZ OF MIAMI UNIVERSITY IS EMPLOYING RADICAL PHOTOPOLYMERIZATION TO PREPARE WELL-DEFINED AND PHOTODEGRADABLE POLYMERS MADE OF VINYL KETONES. POLYVINYL KETONES ARE A CLASS OF POLYMERS THAT ARE WIDELY USED NOT ONLY AS COMPONENTS FOR PACKAGING MATERIALS AND AGRICULTURAL FILMS, BUT ALSO AS FUNCTIONAL PLASTICS IN APPLICATIONS SUCH AS IMAGING, MICROFABRICATION AND SENSORS. AN INTERESTING FEATURE OF THESE POLYMERS IS THAT THEY CAN BE DEGRADED TO THEIR LOW-MOLECULAR WEIGHT FRAGMENT UPON EXPOSURE TO UV IRRADIATION, MAKING THEM IDEALLY SUITABLE FOR RECYCLING. THIS RESEARCH WILL FOCUS ON INVESTIGATING CHEMICAL MECHANISMS OF RADICAL PHOTOPOLYMERIZATION AND PHOTODEGRADATION OF A DIVERSE RANGE OF VINYL KETONES. THE GAINED MECHANISTIC INSIGHTS WILL THEN BE USED TO DEVELOP PHOTO-GATED PLASTICS THAT ARE PREPARED UNDER VISIBLE LIGHT AND DEGRADE UNDER ULTRAVIOLET IRRADIATION. BROADER IMPACTS FROM THE PROJECT WILL INVOLVE THE DEVELOPMENT AND IMPLEMENTATION OF OUTREACH ACTIVITIES THAT ENGAGE MIDDLE AND HIGH SCHOOL STUDENTS. THROUGH THE POLYMER CHEMISTRY AND POLYMER MATERIALS SCIENCE AND ENGINEERING DIVISIONS OF THE AMERICAN CHEMICAL SOCIETY, THE PROJECT WILL ENGAGE MEMBERS OF THE POLYMER CHEMISTRY COMMUNITY BY DEVELOPING EDUCATIONAL RESOURCES THROUGH THE MACROMOLECULAR ALLIANCE FOR COMMUNITY RESOURCES AND OUTREACH (MACRO), AS WELL AS WEBINARS. THE PROJECT WILL ALSO PROVIDE TRAINING AND MENTORING OF GRADUATE AND UNDERGRADUATE STUDENTS OF DIVERSE BACKGROUNDS. UNDERGRADUATE STUDENTS FROM UNDERSERVED GROUPS WILL BE RECRUITED AND MENTORED THROUGH ENGAGEMENT WITH THE LOUIS STOKES ALLIANCE FOR MINORITY PARTICIPATION (LSAMP), WITH A SPECIFIC FOCUS ON PREPARING LSAMP STUDENTS FOR RESEARCH THROUGH FIRST YEAR RESEARCH EXPERIENCE PROJECT. VINYL KETONES ARE UNIQUE PHOTOACTIVE MONOMERS LEADING TO POLYMERS THAT HAVE DISTINCT PHOTO-RESPONSIVE PROPERTIES. HOWEVER, THE FULL POTENTIAL AND BROAD USE OF VINYL KETONES HAS BEEN HINDERED IN PART DUE TO INCOMPLETE UNDERSTANDING OF MONOMER REACTIVITY AND UNDERLYING POLYMERIZATION MECHANISMS. THIS RESEARCH WILL STUDY THE MECHANISM OF RADICAL GENERATION IN VINYL KETONE PHOTOPOLYMERIZATION AND PHOTODEGRADATION. THE DEVELOPED METHODOLOGY COULD OFFER UNIQUE OPPORTUNITIES FOR VINYL KETONES IN REVERSIBLE ADDITION?FRAGMENTATION CHAIN TRANSFER (RAFT) POLYMERIZATION TO ENABLE ACCESS TO DIVERSE FUNCTIONAL GROUPS. DETAILED MECHANISTIC STUDIES WILL ALSO BE PERFORMED TO ADDRESS CHALLENGES IN ATOM TRANSFER RADICAL POLYMERIZATION (ATRP) OF VINYL KETONES AND FURTHER UNDERSTAND PATHWAYS TOWARD EFFICIENT POLYMERIZATION OF THESE COMPLEX MONOMERS. FURTHERMORE, USING THESE MECHANISTIC INSIGHTS INTO THE POLYMERIZATION OF VINYL KETONES, PHOTOCHEMICAL POLYMERIZATION INDUCED SELF-ASSEMBLY (PHOTOPISA) AND PHOTOCHEMICAL DEGRADATION INDUCED MODIFICATIONS OF SELF-ASSEMBLY (PHOTODIMSA) WILL BE PERFORMED TO PROMOTE AND MODULATE THE SELF-ASSEMBLY OF POLYMERS. THE DIMSA APPROACH COULD IMPACT THE POLYMER SELF-ASSEMBLY BROADLY, AS WELL AS TARGETED DELIVERY IN STIMULUS RESPONSIVE POLYMERS. IF THESE STUDIES ARE SUCCESSFUL, NEW ADDITIVE MANUFACTURING AND 3D PRINTING TECHNOLOGIES COULD RESULT, ENABLED BY ORTHOGONAL LIGHT RESPONSIVENESS, WITH ONE WAVELENGTH OF LIGHT SYNTHESIZING ADVANCED POLYMERIC STRUCTURES, AND THE OTHER WAVELENGTH ADDING COMPLEXITY BY POST-POLYMERIZATION DEGRADATION ON SELECTED REGIONS. 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.

INVESTIGATING MEMBRANE PROTEINS WITH MAGNETIC RESONANCE SPECTROSCOPY

THETA MODULATION OF HIPPOCAMPAL ENSEMBLES ACROSS SUBREGIONS

TAS::57 3600::TAS "(YIP 10) CROSS-CONJUGATED NANOARCHITECTURES"

INVESTIGATING MEMBRANE PROTEINS WITH MAGNETIC RESONANCE SPECTROSCOPY

INVESTIGATION OF ER ALPHA EXPRESSION ON MALE BEHAVIOR UNDER FIELD CONDITIONS

IGE: INTERDISCIPLINARY STEM GRADUATE STUDENT LEARNING COMMUNITIES

ESTROGENIC PROTECTION AGAINST COLORECTAL CANCER DEVELOPMENT IN OBESITY - PROJECT SUMMARY SPORADIC COLORECTAL CANCER (CRC), A SUBTYPE OF CRC WITHOUT FAMILY HISTORY BUT ATTRIBUTED TO THE PRESENCE OF VARIOUS RISK FACTORS, IS THE MAJORITY (~75%) OF NEW CRC CASES IN THE US. OBESITY AND RELATED CHRONIC LOW-GRADE INFLAMMATION ARE SIGNIFICANT RISK FACTORS FOR SPORADIC CRC. ALTHOUGH OBESITY PREVALENCE IS HIGHER IN WOMEN THAN IN MEN, PREMENOPAUSAL WOMEN HAVE LOWER INCIDENCES OF CRC THAN AGE-MATCHED MEN. EPIDEMIOLOGY STUDIES HAVE ALSO INDICATED THAT POSTMENOPAUSAL WOMEN INCREASE THEIR RISKS FOR CRC, BUT WOMEN WITH ESTROGEN REPLACEMENT THERAPIES HAVE A SUBSTANTIALLY LOWER INCIDENCE IN CRC. THESE OBSERVATIONS SUGGEST PROINFLAMMATORY ADIPOKINES AND CYTOKINES ASSOCIATED WITH OBESITY AS ONCOGENIC FACTORS, WHEREAS ESTROGEN AS A PROTECTING FACTOR IN CRC DEVELOPMENT. HOWEVER, HOW ESTROGEN SUPPRESSES ADIPOKINE- AND CYTOKINE-INDUCED CRC PATHOGENESIS IS UNCLEAR. THIS KNOWLEDGE GAP IS MAINLY BECAUSE ADIPOKINES/CYTOKINES AND ESTROGEN HAVE BEEN STUDIED AS INDEPENDENT FACTORS IN SEPARATE STUDIES, BUT THEIR INTERACTION HAS NOT BEEN EXPLORED IN CRC. ADDITIONALLY, ALTHOUGH CANCER CELLS HAVE IMPAIRED MITOCHONDRIAL METABOLIC FUNCTION AND ELEVATED ANAEROBIC GLYCOLYSIS (KNOWN AS THE WARBURG EFFECT), MOST RESEARCH ATTENTION HAS BEEN FOCUSED ON STUDYING THE UNDERLYING CELLULAR AND MOLECULAR MECHANISMS, WITHOUT INVESTIGATING THE METABOLIC EVENTS INVOLVED. FURTHER, A SUITABLE OBESITY-ASSOCIATED CRC ANIMAL MODEL IS NEEDED TO RESEMBLE THE EARLY HISTOPATHOLOGIC FEATURES LEADING TO SPORADIC CRC IN HUMANS. IN THIS PROPOSAL, INTERACTION BETWEEN ESTROGEN AND ADIPOKINE LEPTIN OR CYTOKINE IL-6 WILL BE STUDIED IN IN VITRO CELL AND IN VIVO MOUSE MODELS TO UNDERSTAND HOW ESTROGEN PROTECTS AGAINST CRC DEVELOPMENT IN OBESITY SETTING, VIA OPPOSING THE ONCOGENIC ACTIONS OF LEPTIN AND IL-6 AT CELLULAR, MOLECULAR, METABOLIC, AND FUNCTIONAL LEVELS. ADDITIONALLY, ESTROGEN RECEPTOR SS (ERSS) SELECTIVE AGONIST AND SMALL INTERFERING RNA TRANSFECTION TO ERSS THAT SPECIFICALLY REDUCES ERSS EXPRESSION WILL BE USED TO EXPLORE ESTROGENIC MECHANISM. FURTHERMORE, CELL LINES ORIGINALLY OBTAINED FROM PRIMARY TUMORS OF MALE AND FEMALE PATIENTS AND MALE AND FEMALE MICE WITH OBESITY-PROMOTED COLORECTAL TUMORIGENESIS WILL BE INCLUDED, CONSIDERING SEX AS A BIOLOGICAL VARIABLE. FINDINGS OF THIS STUDY IS INVALUABLE FOR IDENTIFYING SEX-SPECIFIC BIOLOGICAL TARGETS FOR INTERVENTION TO PREVENT AND TREAT OBESITY-PROMOTED CRC THAT WOULD BE DIFFERENT BETWEEN MEN AND WOMEN. IMPORTANTLY, THIS PROJECT PROVIDES PLENTIFUL OPPORTUNITIES TO EXPOSE UNDERGRADUATE STUDENTS TO A BROAD RANGE OF MODERN TECHNIQUES SUCH AS QUANTITATIVE REAL-TIME PCR, FLOW CYTOMETRY AND MASS SPECTROMETRY, AND HAVE HANDS-ON PARTICIPATION IN HIGH-QUALITY RESEARCH USING BOTH IN VITRO AND IN VIVO MODELS. THESE ACTIVITIES WILL STRENGTHEN RESEARCH ENVIRONMENT IN CANCER AND METABOLIC RESEARCH AT MIAMI UNIVERSITY, AND FACILITATE COLLABORATIVE RESEARCH OPPORTUNITIES INVOLVING STUDENTS OF DIFFERENT MAJORS FROM DIFFERENT COLLEGES AT MIAMI UNIVERSITY OHIO.

REGULATION OF TYPE-I INTERFERON BY SLAMF9

OLIGODENDROCYTE LINEAGE CELL PLASTICITY IN THE SPINAL CORD FOLLOWING PERIPHERAL INJURY

ATTENTION REGULATION STRATEGIES USED BY DEAF AND HEARING PARENTS OF AUTISTIC CHILDREN - PROJECT SUMMARY DIFFICULTIES WITH SOCIAL COMMUNICATION ARE AMONG THE CORE IMPAIRMENTS OF AUTISM SPECTRUM DISORDERS (ASD) AND POSE SIGNIFICANT CHALLENGES FOR THE ONE IN 44 AMERICAN CHILDREN DIAGNOSED WITH ASD. EARLY DISRUPTIONS IN SOCIAL INTERACTION, ESPECIALLY THE ESTABLISHMENT OF EPISODES OF JOINT ATTENTION BETWEEN CHILDREN AND THEIR PARENTS, ARE BELIEVED TO BE AT THE ROOT OF THE LANGUAGE IMPAIRMENT THAT IS OFTEN COMORBID WITH ASD. DEAF PARENTS HAVE SIGNIFICANT ADVANTAGES OVER HEARING PARENTS IN THEIR ABILITY TO OBTAIN, MAINTAIN, AND DIRECT THE VISUAL ATTENTION OF THEIR CHILDREN. YET THE BEHAVIOR OF DEAF PARENTS OF CHILDREN WITH ASD – HEARING OR DEAF – HAS NEVER BEFORE BEEN STUDIED. THIS PROJECT AIMS TO COMPARE THE ATTENTION-REGULATING STRATEGIES OF DEAF AND HEARING CAREGIVERS OF CHILDREN WITH ASD. FIRST, WE AIM TO STUDY DYADIC INTERACTION BETWEEN DEAF AND HEARING CAREGIVERS AND THEIR CHILDREN WITH ASD IN ORDER TO DETERMINE IF DEAF CAREGIVERS DIFFER FROM HEARING CAREGIVERS IN THE MODALITIES AND STRATEGIES EMPLOYED TO OBTAIN AND MAINTAIN THEIR CHILDREN’S VISUAL ATTENTION. SECOND, WE SEEK TO DETERMINE IF SPECIFIC ATTENTION-REGULATING STRATEGIES RESULT IN MORE AND LONGER EPISODES OF JOINT ATTENTION, SETTING THE STAGE FOR A MORE FAVORABLE ENVIRONMENT FOR LANGUAGE DEVELOPMENT. OVERALL, THE PROJECT AIMS TO LEVERAGE THE BENEFITS OF DEAF ADAPTIVENESS IN THE VISUAL MODALITY OVER THE SOCIAL- COGNITIVE CHALLENGES OF ASD. THE RESULTS WILL ADVANCE OUR UNDERSTANDING OF THE IMPACT THAT PARENT BEHAVIOR HAS ON LANGUAGE AND COGNITIVE DEVELOPMENT, AND WILL INFORM THE DEVELOPMENT OF TRAINING INTERVENTIONS FOR PARENTS OF CHILDREN WITH ASD.

ORTHO-PHENYLENES IN COMPLEX FOLDAMER ARCHITECTURES

IMPROVING SOCIAL COMMUNICATION ASSESSMENT FOR ADOLESCENTS AT RISK FOR COMMUNICATION DISORDERS - PROJECT SUMMARY/ABSTRACT SOCIAL COMMUNICATION DEFICITS ARE COMMON IN ADOLESCENTS WITH HIGH-PREVALENCE DEVELOPMENTAL DISABILITIES (BARIBEAU ET AL, 2015; SKUSE ET AL, 2009; STOREBO ET AL, 2012), AND CONTRIBUTE TO POOR ADULT OUTCOMES (NCWD, 2015). SOCIAL COMMUNICATION INVOLVES ADAPTING LANGUAGE TO A CONTEXT (ROSE-KRASNOR, 1997). INTERVENTION CAN IMPROVE SOCIAL COMMUNICATION SKILLS, BUT TO BE EFFECTIVE, INTERVENTIONS MUST BE TAILORED TO THE ADOLESCENT’S CURRENT LEVEL OF ABILITY FOR RELEVANT CONTEXTS (CAI & RICHDALE, 2016; MCCALL, 2015). TO PLAN EFFECTIVE SOCIAL COMMUNICATION INTERVENTIONS, RESEARCHERS RELY ON CRITERION-REFERENCED ASSESSMENTS. CRITERION-REFERENCED LANGUAGE ASSESSMENTS COMPARE EXAMINEE PERFORMANCE TO A PERFORMANCE STANDARD, SUCH AS THE DEVELOPMENTAL TIMETABLE FOR MASTERING GRAMMATICAL INFLECTIONS. THE TIMETABLE FOR ADOLESCENT SOCIAL COMMUNICATION DEVELOPMENT IS NOT WELL UNDERSTOOD, LEADING CURRENT SOCIAL COMMUNICATION ASSESSMENTS TO INTERPRET PERFORMANCE BY ANOTHER STANDARD, SUCH AS EXPERT JUDGMENTS OF APPROPRIATE OR INAPPROPRIATE RESPONSES. OTHERS HAVE DETERMINED PERFORMANCE LEVEL BY USING RASCH OR IRT ANALYSES TO EMPIRICALLY DETERMINE ITEM DIFFICULTY. NO CURRENT ADOLESCENT SOCIAL COMMUNICATION ASSESSMENTS DETERMINE PERFORMANCE LEVELS BY COMPARING EXAMINEE PERFORMANCE TO LEVELS OF AN INTERPRETIVE FRAMEWORK THAT HAS BEEN VALIDATED BY EMPIRICALLY-DETERMINED ITEM DIFFICULTY. CURRENT ASSESSMENTS ARE NOT DESIGNED TO IDENTIFY ADOLESCENTS’ LEVEL OF SOCIAL COMMUNICATION ABILITY FOR THE TRANSITION TO POST-SCHOOL CONTEXTS SUCH AS EMPLOYMENT OR INDEPENDENT LIVING. EVIDENCE ON HOW MUCH CONTEXT AFFECTS MEASURES OF SOCIAL COMMUNICATION IS LIMITED. TO ADDRESS THESE GAPS IN SOCIAL COMMUNICATION ASSESSMENTS, THE TRANSITION PRAGMATICS INTERVIEW (TPI; POLL & PETRU, 2018) HAS BEEN DEVELOPED. THE GOAL OF THIS PROJECT IS TO TEST THE DESIGN OF THE TPI AS COMPARING THE EXAMINEE’S ABILITY LEVEL TO AN EMPIRICALLY-VALIDATED INTERPRETIVE FRAMEWORK. ITEMS OF THE TPI WILL BE DESIGNED TO VARY IN DIFFICULTY BASED ON THE LEVELS OF THE INTERPRETIVE FRAMEWORK, THE SITUATIONAL-DISCOURSE-SEMANTICS MODEL. BASED ON A FIELD TEST OF THIS REFINED TPI ITEM SET, ITEM DIFFICULTY WILL BE EVALUATED USING RASCH ANALYSES. LEVELS OF THE INTERPRETIVE FRAMEWORK WILL BE EVALUATED AS PREDICTORS OF ITEM DIFFICULTY. TO EVALUATE HOW CONTEXT AFFECTS SOCIAL COMMUNICATION, FIELD TEST PARTICIPANTS WILL BE EVALUATED WITH FOUR SUBSCALES OF THE TPI, EACH FOCUSED ON A POST-SCHOOL CONTEXT. RASCH ANALYSES WILL USED TO DETERMINE PARTICIPANT ABILITIES FOR EACH POST-SCHOOL CONTEXT ON AN EQUIVALENT SCALE. FINALLY, THE CONTEXT-FOCUSED SUB-SCALES OF THE TPI WILL EACH BE EVALUATED TO DETERMINE THEIR DIMENSIONALITY. TAKEN TOGETHER, THESE WILL BE MAJOR STEPS IN THE DEVELOPMENT OF A PSYCHOMETRICALLY-SOUND MEASURE OF ADOLESCENT SOCIAL COMMUNICATION TAILORED TO TRANSITION INTERVENTION PLANNING.

A STAND-ALONE SIMULATION PLATFORM FOR DESIGNING TISSUE ENGINEERING SCAFFOLDS TO SERVE AS BONE GRAFT SUBSTITUTES - PROJECT SUMMARY THE HIGH-VALUE MARKET FOR BONE GRAFT MATERIALS IS A MAJOR STIMULUS FOR DEVELOPING INNOVATIVE AND MORE EFFECTIVE PRODUCTS. THIS STUDY CAN PROVIDE AN ATTRACTIVE ALTERNATIVE TO THE COMMERCIALLY-AVAILABLE BONE GRAFT SUBSTITUTES. WE WILL DEVELOP A SIMULATION PLATFORM FOR DESIGNING TISSUE ENGINEERING SCAFFOLDS TO SERVE AS BONE GRAFT SUBSTITUTES. THE APPLICATION BUILDER™ FUNCTIONALITY IN COMSOL® SOFTWARE WILL BE USED TO DEVELOP A STAND-ALONE USER-FRIENDLY DESIGN TOOL FREELY ACCESSIBLE TO STUDENTS, EDUCATORS, AND RESEARCHERS ACROSS THE UNITED STATES. NO COMSOL® LICENSE WILL BE REQUIRED, AND THE APPLICATION (APP) WILL BE AVAILABLE FOR WINDOWS®, MACOS®, AND LINUX®. THIS WILL ENABLE NON-DOMAIN SPECIALISTS (E.G., SCIENTISTS WITH LIMITED EXPERTISE IN MODELING) TO DESIGN 3D SCAFFOLDS WITH OPTIMAL COMPOSITION AND PROPERTIES. WE HAVE SHOWN THAT 3D-SCAFFOLDS CAN BE OPTIMIZED USING COMSOL® TO ATTAIN THE BIOMECHANICAL REQUIREMENTS AND POROSITY CONSTRAINTS FOR BONE TISSUE ENGINEERING (BIOFABRICATION, 2017). THE STUDY OUTLINED IN THIS PROPOSAL WILL FURTHER OPTIMIZE THE SCAFFOLD ARCHITECTURE AND COMPOSITION BY COMBINING NUMERICAL OPTIMIZATION VIA COMSOL® (A FINITE-ELEMENT MODELING SOFTWARE), I-OPTIMAL DESIGN OF EXPERIMENTS (DOE) VIA JMP® (A STATISTICAL DESIGN SOFTWARE), WHILE ELIMINATING THE EXTRUDATE SWELL TO GENERATE DESIGN-DRIVEN ARCHITECTURES AND ENHANCE REPRODUCIBILITY. THE JMP® FUNCTIONALITY WILL BE INCORPORATED INTO THE APP AS A USER-DEFINED MODEL. WE WILL DESIGN 3D-PLOTTED COMPOSITES MADE OF SLOW-DEGRADING AND FAST- DEGRADING ZONES AND OPTIMIZE THE DESIGN USING COMSOL® AND JMP®. THE SLOW-DEGRADING COMPONENT OF THE HYBRID SCAFFOLDS WILL BE COMPOSED OF POLY(L-LACTIC ACID) (PLLA) AND NANO-HYDROXYAPATITE (NHA), WHEREAS THE FAST- DEGRADING COMPONENT WILL BE MADE OF POLY(LACTIC-CO-GLYCOLIC ACID)(PLGA), COLLAGEN (COL), AND NHA. MICROPORES WILL BE GENERATED WITHIN THE FAST-DEGRADING COMPONENT UPON THE EXTRACTION OF POLYETHYLENE GLYCOL (PEG) POROGEN. THE SLOW-DEGRADING COMPONENT WILL ALLOW MAINTAINING SUFFICIENT MECHANICAL PROPERTIES TO SUPPORT TISSUE GROWTH AFTER THE EROSION OF THE FAST-DEGRADING COMPONENT. WE ANTICIPATE THAT THE FAST-DEGRADING ZONES WILL ALSO OVERCOME THE TRANSPORT LIMITATIONS ONCE IMPLANTED IN VIVO (FUTURE STUDIES). A KEY REQUIREMENT FOR BIOENGINEERED BONE GRAFT SUBSTITUTES IS THE ABILITY TO PROVIDE THE CAPACITY FOR REMODELING AND RAPID RESTORATION OF THE BIOMECHANICAL FUNCTION. OUR SPECIFIC AIMS ARE: (AIM 1) DESIGN NON-HYBRID AND HYBRID SCAFFOLDS WITH A MODULUS WITHIN THE RANGE OF BONE (COMSOL®), (AIM 2) EVALUATE THE IN VITRO CELLULAR ACTIVITY AND OPTIMIZE THE SCAFFOLD COMPOSITION (JMP®), AND (AIM 3) EVALUATE THE OPTIMIZED SCAFFOLD INSIDE A BIOREACTOR AND DEVELOP/VALIDATE THE COMSOL® APP. WE WILL VALIDATE THE PROPOSED SIMULATION APP USING OUR HYBRID 3D SCAFFOLDS. IN AIM 3, FOUR ADDITIONAL MATERIALS WILL ALSO BE TESTED FOR THE VALIDATION OF THE APP. THE OUTCOMES WILL BE COMPARED WITH THE 3D SCAFFOLD DESIGNS REPORTED IN THE SCIENTIFIC LITERATURE. WE WILL SHOWCASE THE SOFTWARE VIA LINKEDIN, WEBINARS, CONFERENCES, AND OHIO LIFE SCIENCES NETWORK. THE SOFTWARE COULD ALSO BE USED FOR CARTILAGE TISSUE ENGINEERING. ADAPTING THE SOFTWARE TO OSTEOCHONDRAL AND VASCULAR TISSUES ENGINEERING WILL BE CONSIDERED IN OUR NEXT STUDIES.

GENETIC AND EPIGENETIC EFFECTS OF TRANSPOSABLE ELEMENTS ON MEIOTIC RECOMBINATION

DECISION MAKING UNDER STRESS

CAUSES AND CONSEQUENCES OF VIRULENCE FACTOR ATTENUATION IN MYCOPLASMA PNEUMONIAE BIOFILMS - HOW THE HUMAN PATHOGEN MYCOPLASMA PNEUMONIAE ATTENUATES VIRULENCE FACTOR PRODUCTION DURING GROWTH AS BIOFILM TOWERS, AND HOW THIS ATTENUATION FAVORS CHRONIC RESPIRATORY DISEASE, INCLUDING BOTH PNEUMONIA AND ASTHMA, ARE UNKNOWN. OUR LONG-TERM GOAL IS TO UNDERSTAND THE PROCESSES THAT ARE ESSENTIAL FOR ESTABLISHING AND MAINTAINING M. PNEUMONIAE INFECTION. THE OVERALL OBJECTIVE OF THIS APPLICATION IS TO UNDERSTAND HOW M. PNEU- MONIAE BIOFILM TOWERS CHRONICALLY INFECT RESPIRATORY EPITHELIAL HOST CELLS AT AN AIR-LIQUID INTERFACE (ALI). OUR CENTRAL HYPOTHESIS IS THAT THE REDUCTION IN VIRULENCE FACTOR PRODUCTION BY M. PNEUMONIAE BACTERIA IN BIOFILM TOWERS IS SIGNALED BY DECREASED O2 LEVELS AND RESULTS IN MINIMIZATION OF BOTH DEFENSIVE RESPONSES AND DAMAGE TO THE EPITHELIUM. THE RATIONALE UNDERLYING THESE EXPERIMENTS IS THAT ONCE THE EXTENT TO WHICH DAMAGE IS LIMITED BY CHANGES TO M. PNEUMONIAE DURING BIOFILM TOWER GROWTH AND MAINTENANCE IS UNDERSTOOD, APPROACHES THAT COUNTER THE SCHEME OF LIMITING HOST RESPONSES COULD BE DEVELOPED AS THERAPEUTIC AGENTS TO REDUCE MORBIDITY ASSOCIATED WITH CHRONIC M. PNEUMONIAE INFECTION. WE PLAN TO TEST OUR CENTRAL HYPOTHESIS BY PURSUING THE FOLLOW- ING TWO SPECIFIC AIMS: 1) CHARACTERIZE THE DEVELOPMENT AND IMPACT OF M. PNEUMONIAE BIOFILMS IN A RESPIRATORY EPITHELIAL AIR-LIQUID INTERFACE TISSUE CULTURE MODEL; AND 2) DETERMINE THE ROLE OF O2 IN REGULATING M. PNEUMONIAE GENE EXPRESSION AND STEADY-STATE LEVELS OF VIRULENCE-ASSOCIATED PROTEINS IN VITRO. FOR THE FIRST AIM, WE WILL CHAR- ACTERIZE THE IMPACT OF M. PNEUMONIAE BIOFILM TOWERS ON AIRWAY EPITHELIA IN AN ALI TISSUE CULTURE MODEL USING MICROSCOPY, TRANSCRIPTOMICS OF THE HOST CELLS, AND MEASUREMENTS OF EPITHELIAL BARRIER FUNCTION LIKE TRANSEPITHELIAL ELECTRICAL RESISTANCE, CILIATION, AND LOCALIZATION OF THE ZO-1 TIGHT JUNCTION PROTEIN, COMPARING THESE EFFECTS TO THOSE PRODUCED BY CARDS TOXIN AND H2O2, TOXIC MOLECULES WHOSE PRODUCTION IS ATTENUATED IN M. PNEUMONIAE DURING BIOFILM TOWER GROWTH. FOR THE SECOND AIM, PROMPTED BY PRELIMINARY DATA ABOUT THE DECREASED ACTIVITY OF THE H2O2-PRODUCING ENZYME GLYCEROL 3-PHOSPHATE OXIDASE IN M. PNEUMONIAE GROWN IN LOW O2, WE WILL INVESTIGATE THE BACTERIAL RESPONSE TO GROWTH IN 10% O2 AT THE LEVELS OF TRANSCRIPTION A GLOBAL LEVEL, AND, FOR SELECT VIRULENCE- ASSOCIATED PROTEINS, STEADY-STATE ABUNDANCE. THE PROPOSED RESEARCH IS INNOVATIVE, IN OUR OPINION, BECAUSE IT REPRESENTS A SUBSTANTIVE DEPARTURE FROM THE STATUS QUO BY FOCUSING ON HOW M. PNEUMONIAE BOTH RESPONDS TO AND IMPACTS ITS ENVIRONMENT WITHIN A BIOFILM CONTEXT, USING BIOFILM TOWER GROWTH IN AN ALI AIRWAY EPITHELIAL MODEL AND STUDYING GENE REGULATION IN A BIOFILM ENVIRONMENT. THIS CONTRIBUTION WILL BE SIGNIFICANT BECAUSE IT IS EXPECTED TO DIRECT FUTURE RESEARCH EFFORTS TOWARD DEVELOPMENT OF THERAPEUTIC INTERVENTION STRATEGIES TARGETING M. PNEU- MONIAE BIOFILMS. ADDITIONALLY, THE WORK IN THIS AREA PROPOSAL WILL PROVIDE TRAINING IN FUNDAMENTAL MICROBIO- LOGICAL, TRANSCRIPTOMIC, AND TISSUE CULTURE TECHNIQUES FOR 4-5 UNDERGRADUATE AND A GRADUATE STUDENT WITH CAREER INTERESTS IN PARTICULAR AREAS OF BIOMEDICAL RESEARCH, WITH A SIGNIFICANT EFFORT TO INCLUDE UNDERREPRESENTED MINOR- ITIES.

BIOPHYSICAL STUDIES OF TWIN ARGININE TRANSPORT COMPONENT MEMBRANE INSERTION

INVESTIGATING MEMBRANE PROTEINS WITH MAGNETIC RESONANCE SPECTROSCOPY

ANALYSIS OF AN NHE INHIBITOR SIGNALING PATHWAY THAT REGULATES SPERM MOTILITY.

EXPRESSION CONTROL IN DROSOPHILA SPLICING ASSEMBLY FACTOR RNP-4F

LIPID OVERLOAD AND SKELETAL MUSCLE ENERGETICS.

METABONOMICS STUDIES OF HUMAN DISEASES

TIME-DEPENDENT STRUCTURAL STUDIES ON DINUCLEAR METAL ION CONTAINING ENZYMES

INTERACTIVE ROLES OF CARDIORESPIRATORY FITNESS AND ADIPOSITY ON RECOVERY OF IMPAIRED GLUCOSE AND VASCULAR CONTROL AFTER PHYSICAL INACTIVITY - PROJECT SUMMARY THE FAR-REACHING NEGATIVE HEALTH EFFECTS OF THE REDUCED PHYSICAL ACTIVITY (RPA) EPIDEMIC ARE OFTEN OVERLOOKED BY THE GENERAL POPULATION AND HEALTH PROFESSIONALS. SHORT-TERM RPA INDUCES CARDIOMETABOLIC DYSFUNCTION, INCLUDING IMPAIRED GLUCOSE CONTROL AND VASCULAR FUNCTION, THAT MAY PRECEDE DISEASE DEVELOPMENT. THE IMPACT OF EXISTING HEALTH STATUS ON RPA-INDUCED CARDIOMETABOLIC DYSFUNCTION AND RECOVERY OF IMPAIRED GLUCOSE CONTROL FOLLOWING RPA IS UNEXPLORED. THUS, OUR OBJECTIVES ARE 1) TO INVESTIGATE THE EFFECT OF EXISTING HEALTH STATUS (CARDIORESPIRATORY FITNESS AND ADIPOSITY) ON THE RECOVERY OF IMPAIRED GLUCOSE CONTROL FOLLOWING A PERIOD OF RPA AND 2) TO DETERMINE THE ROLE OF VASCULAR FUNCTION AS A MECHANISM OF IMPAIRED GLUCOSE CONTROL. OUR FINAL OBJECTIVE IS TO 3) EXPOSE UNDERGRADUATE STUDENTS TO MERITORIOUS BIOMEDICAL CLINICAL RESEARCH METHODS. WE HAVE PILOTED THE CLINICAL RESEARCH METHODS AND ANALYSIS WITH UNDERGRADUATE RESEARCHER ASSOCIATES AND ARE WELL-PREPARED TO COMPLETE THIS PROPOSAL. OUR PRELIMINARY DATA SHOW THAT LOW CARDIORESPIRATORY FITNESS AND/OR HIGH ADIPOSITY IMPAIR THE RECOVERY OF GLUCOSE CONTROL FOLLOWING SHORT-TERM RPA. THUS, WE AIM TO EXAMINE THE INTERACTIVE ROLE OF HEALTH STATUS (CARDIORESPIRATORY FITNESS AND ADIPOSITY) ON THE ABILITY TO RECOVER IMPAIRED GLUCOSE CONTROL FOLLOWING SHORT-TERM RPA. WE ALSO SEEK TO EXAMINE CHANGES IN VASCULAR FUNCTION AS A MECHANISM OF RECOVERY OF IMPAIRED GLUCOSE CONTROL FOLLOWING A RETURN TO NORMAL PA. WE WILL RECRUIT MEN AND WOMEN WITH DIVERGENT HEALTH STATUS (CARDIORESPIRATORY FITNESS AND ADIPOSITY) TO EXAMINE GLUCOSE CONTROL AND VASCULAR FUNCTION DURING 7-D OF NORMAL PA, 7-D OF RPA, AND 7-D OF RESUMPTION OF NORMAL RA. CONTINUOUS GLUCOSE MONITORING AND ORAL GLUCOSE TOLERANCE TESTS WILL BE PERFORMED TO ASSESS GLUCOSE CONTROL. INCREASES IN VASCULAR SHEAR STRESS INDUCED BY PASSIVE LEG MOVEMENT AND CENTRAL ARTERIAL STIFFNESS WILL BE MEASURED TO ASSESS VASCULAR FUNCTION.

DECADES OF CONFLICT COLONIALISM GROWING POPULATION AND GLOBAL AGRICULTURE COMMERCIALIZATION HAVE RESULTED IN LAND-COVER/LAND-USE CHANGE (LCLUC) ON MULTIPLES SPATIAL SCALES THROUGHOUT SOUTHEAST ASIA. THESE CHANGES HAVE HAD A PROFOUND IMPACT ON THE ETHNIC MINORITIES PARTICULARLY IN SOUTHERN VIETNAM. VIETNAM HAS EXPERIENCED SIGNIFICANT POLITICAL ECONOMIC AND ENVIRONMENTAL CHANGE SINCE THE 1950S AND THE END OF COLONIALISM AND FRENCH INDOCHINA. ALL LCLUC IN VIETNAM MUST CONSIDER THE IMPACTS OF THE VIETNAM WAR AND SUBSEQUENT REGIONAL AND INTERNAL CONFLICTS THE ESTABLISHMENT OF THE ONE PARTY GOVERNMENT UNDER THE COMMUNIST PARTY OF VIETNAM RECENT MARKET AND TRADE LIBERALIZATION AND A COMPLEX RELIGIOUS AND SOCIOCULTURAL TAPESTRY. THIS PROJECT FOCUSES ON THE NG TH P AND AN GIANG PROVINCES OF THE MEKONG DELTA REGION WHICH ARE HOME TO SOME OF VIETNAM'S LARGEST ETHNIC MINORITIES INCLUDING KHMERS AND CHAM PEOPLE. THEY ARE ALSO HOME TO A UNIQUELY VIETNAMESE FORM OF BUDDHISM H A HO WHICH FIGURES IMPORTANTLY IN THE MODERN HISTORY AND LANDSCAPE OF THE REGION. H A HO EMPHASIZES THE CONNECTION OF AN INDIVIDUAL TO THE LAND IN A RELATIONSHIP THAT IS INTIMATELY ETHICAL SPIRITUAL AND NATIONAL. THE ADVENT OF THE SATELLITE ERA ENABLES STUDIES OF THE PHYSICAL CHANGES ON THE ENVIRONMENT BUT TO FULLY UNDERSTAND THE TRAJECTORY OF LANDSCAPE CHANGE IT IS NECESSARY TO INCORPORATE THE SOCIAL AND RELIGIOUS FACTORS ENDEMIC TO THE REGION. WE PROPOSE TO MAP THE CHANGES AND MODEL THE FUTURE TRAJECTORY OF LCLUC BY INCORPORATING A SOCIOCULTURAL FRAMEWORK IN A SPATIAL MODELING ENVIRONMENT FOR THE MEKONG DELTA REGION OF SOUTHERN VIETNAM WITH HUMANISTIC AND SOCIOLOGICAL STUDIES COMBINED WITH VERY HIGH RESOLUTION LCLUC IN THE NG TH P AND AN GIANG PROVINCES. THIS PROJECT WILL MAP ALL AGRICULTURAL FOREST AND URBAN LCLUC AROUND THE TR M CHIM NATIONAL PARK IN NG TH P PROVINCE AGRICULTURAL AREAS IN BOTH PROVINCES AND THE TWO CITIES OF CAO L NH NG TH P PROVINCE AND LONG XUY N AN GIANG PROVINCE USING LANDSAT AND VERY HIGH RESOLUTION (VHR) DIGITAL GLOBE DATA FROM NASA COMMERCIAL ARCHIVE DATA FOR YEARS 1985 TO 2018. IN YEAR 3 THE VHR LCLUC MAPPING WILL EXTEND TO THE ENTIRE MEKONG DELTA REGION. THIS PROJECT WILL UTILIZE DECISION TREE ALGORITHMS WITHIN A DATA SCIENCE APPROACH TO MINE THE LANDSAT ARCHIVE AND WORLDVIEW-1 -2 AND -3 DATA ON THE LARGE COMPUTING CAPACITY OF THE ADVANCED DATA ANALYTICS PLATFORM (ADAPT) AT NASA GSFC S NCCS (HTTP:// WWW.NCCS.NASA.GOV/SERVICES/ADAPT). USING A MIXED METHODS APPROACH OF HISTORICAL DOCUMENTATION IN-COUNTRY INTERVIEWS QUALITATIVE METHOD OF CULTURAL VIGNETTES AND QUANTITATIVE METHODS OF SOCIOECONOMIC DEVELOPMENT PATHWAYS WE WILL EXTRACT HISTORICAL CURRENT AND FUTURE LAND COVER/LAND USE CHANGE TRAJECTORIES AND THEORIES OF CHANGE. HISTORICAL DOCUMENTS WILL BE RETRIEVED IN-COUNTRY AND FROM THE U.S. LIBRARY OF CONGRESS. IN ADDITION TO SOCIOECONOMIC DATA THIS PROJECT WILL FOCUS ON THE IMPACT OF CONFLICT RELIGION AND POLITICAL CHANGES ON LCLUC. THESE SOCIOCULTURAL AND SOCIOECONOMIC VARIABLES ARE IMPORTANT GIVEN THE COMPLEX RELIGIOUS ETHNIC AND ECONOMIC TAPESTRY OF THE REGION. THESE THEORIES OF CHANGE WILL BE USED TO CREATE SCENARIOS OF FUTURE LCLUC MAPPED TO BOOLEAN GRIDS (SWETNAM ET AL. 2010) AND TESTED AGAINST A MARKOV CHAIN APPROACH. GIS MODELS OF FUTURE LCLUC WILL COMBINE THE REMOTE SENSING-DERIVED PRODUCTS WITH THE SPATIALLY EXPLICIT THEORIES OF CHANGE AND OTHER SUITABILITY VARIABLES WITHIN GEOSTATISTICAL WEIGHTED MODELS AND TESTED AGAINST THE LARGE REGION. WORKING WITH OUR IN-COUNTRY COLLABORATOR OPEN SOURCE WEB VISUALIZATION AND ATLAS.TI KML LINKED FILE WILL BE CREATED TO DISPLAY HISTORICAL CURRENT AND PREDICTED SPATIALLY-EXPLICIT 10-30 M RESOLUTION LCLUC OF THESE TWO PROVINCES. ALL DATA PRODUCTS CREATED IN THE PROJECT WILL BE SHARED IN COLLABORATION WITH THE NASA SERVIR-MEKONG PROJECT LED BY COLLABORATOR POTAPOV.

MODULATION OF NETWORK FEEDBACK SHIFTS THE LOCUS OF RHYTHM GENERATION - CENTRAL PATTERN GENERATOR (CPG) NETWORKS CONTROL IMPORTANT RHYTHMIC BEHAVIORS SUCH AS CHEWING, BREATHING, AND LOCOMOTION. CPGS MUST CONTINUOUSLY ADAPT TO PHYSIOLOGICAL AND ENVIRONMENTAL CHALLENGES, CONVEYED VIA SENSORY PATHWAYS, TO MAINTAIN HEALTHY FUNCTION. DYSFUNCTION OF CPGS OR THEIR INPUTS DUE TO NEUROLOGICAL DISORDERS OR STROKE-INDUCED DAMAGE ALTERS CPG FUNCTION AND ADAPTABILITY, WHICH DECREASES HEALTH AND QUALITY OF LIFE. ONE WAY IN WHICH CPG NETWORKS ADAPT IS THROUGH CHANGES IN THE SPATIAL DISTRIBUTION OF THEIR ACTIVE COMPONENTS, SUCH AS MAMMALIAN RESPIRATORY CPG ACTIVITY VARYING ALONG A BRAINSTEM COLUMN. HOWEVER, LITTLE IS KNOWN ABOUT THE CELLULAR-LEVEL MECHANISMS BY WHICH SENSORY PATHWAYS TRIGGER CHANGES IN THE SPATIAL DISTRIBUTION OF CPGS, AND HOW SUCH CHANGES MAY ALTER THE MECHANISMS OF RHYTHM GENERATION. SENSORY PATHWAYS INFLUENCE CPGS DIRECTLY OR BY ACTIVATING PROJECTION NEURON INPUTS TO CPGS. PROJECTION NEURON ACTIVITY, WHICH IS FURTHER REGULATED BY SYNAPTIC FEEDBACK FROM THEIR TARGET CPGS, DETERMINES CPG OUTPUT. CPG FEEDBACK STRENGTH IS FLEXIBLE, AND FEEDBACK CAN LINK DIFFERENT NERVOUS SYSTEM REGIONS. THUS, THE CENTRAL HYPOTHESIS OF THIS PROPOSAL IS THAT SENSORY MODULATION OF CPG FEEDBACK CAN ALTER RHYTHM GENERATION LOCUS AND MECHANISM. SMALL INVERTEBRATE NEURAL NETWORKS HAVE ENABLED MUCH INSIGHT INTO NETWORK PLASTICITY DUE TO HAVING FEWER NEURONS WITH WELL-DESCRIBED CONNECTIVITY, AND COMPLETE CPGS THAT CAN BE MAINTAINED IN VITRO. IN THIS PROPOSAL, AN IN VITRO STOMATOGASTRIC NERVOUS SYSTEM (STNS) PREPARATION FROM THE CRAB (CANCER BOREALIS) WILL PROVIDE EXCEPTIONAL ACCESS TO IDENTIFIED SENSORY, CHEWING CPG, FEEDBACK, AND PROJECTION NEURONS. SENSORY ACTIVATION OF DISTINCT CHEWING RHYTHMS, PHOTOINACTIVATION OF IDENTIFIED NEURONS AND NEURONAL COMPARTMENTS, HYBRID COMPUTATIONAL-BIOLOGICAL NETWORKS, AND INDEPENDENT MANIPULATION OF LOCAL AND DISTANT SYNAPTIC ACTIONS OF A FEEDBACK NEURON WILL BE USED TO IDENTIFY CELLULAR AND SYNAPTIC MECHANISMS CONTROLLING RHYTHM GENERATION LOCUS IN DIFFERENT MODULATORY STATES. IT IS EXPECTED THAT A NOVEL MECHANISM FOR ALTERING CPG SPATIAL DISTRIBUTION WILL BE IDENTIFIED, NAMELY MODULATION OF CPG FEEDBACK STRENGTH AND INCORPORATION OF THIS FEEDBACK INTO RHYTHM GENERATION. IT IS FURTHER PREDICTED THAT ALTERING RHYTHM GENERATION LOCUS IN THIS MANNER IS A NOVEL MECHANISM FOR REGULATING THE ACCESS OF SENSORY PATHWAYS TO A MOTOR SYSTEM. AN INCREASED CELLULAR-LEVEL UNDERSTANDING OF THE DYNAMICS OF RHYTHM GENERATION LOCUS IS IMPORTANT FOR FUTURE INVESTIGATION INTO HOW DAMAGE OR DYSFUNCTION MAY CHANGE CPG ADAPTABILITY. IDENTIFYING NOVEL PRINCIPLES IN A SMALL WELL-DEFINED SYSTEM WILL GUIDE STUDIES OF INTERACTIONS BETWEEN SENSORY AND CPG FEEDBACK PATHWAYS THAT REGULATE CPG SPATIAL DISTRIBUTION IN LARGER NERVOUS SYSTEMS DURING BOTH FUNCTIONAL AND DYSFUNCTIONAL STATES. FURTHER, THIS PROPOSAL WILL PROVIDE RESEARCH AND NETWORKING OPPORTUNITIES FOR STUDENTS, INCLUDING EXPERIENCE IN CUTTING-EDGE ELECTROPHYSIOLOGICAL TECHNIQUES, QUANTITATIVE DATA ANALYSIS SKILLS, AND ORAL AND WRITTEN SCIENTIFIC COMMUNICATION SKILLS, HELPING TO FILL A LARGE, UNMET DEMAND FOR NEUROSCIENCE RESEARCH OPPORTUNITIES AT MIAMI UNIVERSITY.

COLLABORATIVE PROPOSAL: ROLES FOR DEHYDRATION AND PHOTOPERIODISM IN PREPARING AN ANTARCTIC INSECT FOR THE POLAR NIGHT

TEACH CINCINNATI: CINCINNATI-BASED SUPPORT

RUI: INVESTIGATION OF GENES AND COMPLEX SOCIAL BEHAVIOR UNDER ECOLOGICALLY RELEVANT CONDITIONS

MIAMI UNIVERSITY HUMANITIES CENTER NEH CHALLENGE GRANT APPLICATION

FCRL1 IN B CELL DIFFERENTIATION - PROJECT SUMMARY B LYMPHOCYTES ARE RESPONSIBLE FOR MAKING ANTIBODIES IN RESPONSE TO ANTIGENS FROM VACCINATION AND INFECTION. ADAPTIVE IMMUNITY INVOLVES ACTIVATING AND EXPANDING B CELLS THAT CAN RECOGNIZE THOSE ANTIGENS, PRODUCE NEUTRALIZING AND OPSONIZING ANTIBODIES, AND PROVIDE IMMUNOLOGICAL MEMORY. THE PROCESS BY WHICH THIS OCCURS INVOLVES A COMPLEX INTERPLAY OF SIGNALS INSIDE AND OUTSIDE THE CELL TO INSTRUCT B CELLS WHEN TO EXPAND, MODIFY THEIR ANTIGEN RECEPTOR, AND DIFFERENTIATE INTO MEMORY CELLS OR ANTIBODY-SECRETING PLASMA CELLS. MUCH OF THIS DIFFERENTIATION PROCESS OCCURS IN A SPECIALIZED LYMPHOID STRUCTURE CALLED THE GERMINAL CENTER. OUR STUDY SEEKS TO UNDERSTAND HOW B CELLS NAVIGATE THE GROWTH AND DIFFERENTIATION PROCESS TO OPTIMIZE ANTIBODY RESPONSES. WE ARE STUDYING A CELL SURFACE PROTEIN, FCRL1, FOUND ON ALL SUBSETS OF PERIPHERAL B CELLS. WHEN THE B CELL RECEPTOR (BCR) IS ENGAGED BY ANTIGEN, FCRL1 ENHANCES INTRACELLULAR CALCIUM SIGNALS WHILE SUPPRESSING THE ACTIVATION OF ERK1/2. MICE DEFICIENT IN FCRL1 HAVE IMPAIRED ANTIBODY RESPONSES AND FEWER GERMINAL CENTER B CELLS AFTER IMMUNIZATION. WE HYPOTHESIZE THAT FCRL1 IS CONTROLLING B CELL SIGNALS TO MAXIMIZE CLONAL EXPANSION PRIOR TO DIFFERENTIATION. USING A MODEL ANTIGEN SYSTEM AND FCRL1-/- MICE, THIS STUDY WILL TRACK THE KINETICS OF B CELL ACTIVATION AND DIFFERENTIATION THROUGHOUT THE GERMINAL CENTER RESPONSE TO THE PRODUCTION OF MEMORY AND PLASMA CELLS. IT WILL EXAMINE HOW FCRL1-MEDIATED ERK INHIBITION ALTERS B CELL DIFFERENTIATION, AND IT WILL BEGIN TO UNCOVER THE SIGNALING PATHWAY(S) USED BY FCRL1 TO DOWN-MODULATE BCR-INDUCED ERK1/2 ACTIVATION USING GENE-TARGETED AND TRANSGENIC B CELL LINES. THIS STUDY WILL IMPROVE OUR UNDERSTANDING OF SIGNALS THAT PROVIDE OPTIMAL ANTIBODY RESPONSES TO INFECTION WITH THE LONG-TERM AIM OF IMPROVING THE EFFICACY AND DURABILITY OF VACCINES AND IMMUNOTHERAPIES.

MECHANISMS OF CARDIOMYOCYTE-EXTRACELLULAR MATRIX INTERACTIONS IN CARDIOGENESIS - SUMMARY PROPER HEART DEVELOPMENT IS ESSENTIAL FOR EFFICIENT HEART FUNCTION THROUGHOUT LIFE. CONGENITAL HEART DEFECTS (CHDS) ARE THE MOST COMMON CONGENITAL MALFORMATIONS, OCCURRING IN UP TO 1% OF LIVE BIRTHS AND 10% OF STILL BIRTHS. CHDS CAN ALSO LEAD TO INCREASED RISK OF CARDIOVASCULAR DISEASES IN ADULTS. DURING VERTEBRATE HEART DEVELOPMENT, CARDIOMYOCYTE PROGENITORS ARE SURROUNDED BY A RICH EXTRACELLULAR MATRIX (ECM). MUTATIONS IN SEVERAL ECM PROTEINS IN HUMANS CAN LEAD TO CHDS. HOWEVER, THE MECHANISMS UNDERLYING CHDS ASSOCIATED WITH MUTATIONS THAT AFFECT THE ECM REMAIN POORLY UNDERSTOOD. SIGNALS FROM THE ECM ARE DETECTED BY INTEGRIN RECEPTORS ON TARGET CELLS. OUR PRELIMINARY ANALYSIS OF ZEBRAFISH CARRYING LOSS-OF-FUNCTION MUTATIONS IN BOTH THE INTEGRIN ALPHA5 AND INTEGRIN ALPHA4 GENES INDICATE THAT THESE INTEGRINS ARE REITERATIVELY REQUIRED TO PROMOTE PROPER CARDIAC MORPHOGENESIS AND VENTRICLE SIZE. THE OVERALL GOAL OF THIS PROPOSAL IS TO ELUCIDATE MECHANISMS BY WHICH CARDIOMYOCYTES INTERPRET AND INTEGRATE SIGNALS FROM THE ECM TO EXECUTE PROPER CARDIOMYOCYTE MIGRATION AND HEART GROWTH. THE SPECIFIC AIMS OF THIS PROPOSAL ARE: AIM 1 - DETERMINE MECHANISMS BY WHICH INTEGRIN SIGNALING MEDIATES PROPER CARDIOMYOCYTE MIGRATION. THIS AIM WILL USE HISTOLOGICAL TECHNIQUES AND CONFOCAL TIME LAPSE MICROSCOPY OF LIVE EMBRYOS TO TEST THE HYPOTHESIS THAT INTEGRIN SIGNALING PROMOTES DIRECTED CARDIOMYOCYTE MIGRATION BY ESTABLISHING AN ORGANIZED, POLARIZED EPITHELIUM; AIM 2 - DETERMINE THE ROLE OF INTEGRINS IN VENTRICLE DEVELOPMENT. THIS AIM COMBINES CARDIOMYOCYTE NUMBER QUANTIFICATION AND TEMPORAL DIFFERENTIATION ASSAYS TO TEST THE HYPOTHESIS THAT INTEGRINS DRIVE HEART GROWTH BY PROMOTING ADDITION OF LATER- DIFFERENTIATING SECOND HEART FIELD (SHF) CARDIOMYOCYTES TO THE VENTRICLE AND OUTFLOW TRACT; AIM 3 - DETERMINE THE TISSUE-SPECIFIC AND TEMPORAL REQUIREMENTS FOR INTEGRINS IN PROMOTING CARDIOMYOCYTE MIGRATION AND SHF ADDITION. THIS AIM USES NOVEL TRANSGENIC LINES TO SPATIALLY AND TEMPORALLY REGULATE INTEGRIN EXPRESSION TO TEST THE HYPOTHESIS THAT INTEGRIN SIGNALING ACTS SPECIFICALLY IN THE CARDIOMYOCYTES, FIRST TO PROMOTE CARDIOMYOCYTE MIGRATION, AND LATER TO PROMOTE SECOND HEART FIELD ADDITION. BY ILLUMINATING HOW DIFFERENT CARDIOMYOCYTE POPULATIONS INTEGRATE AND INTERPRET SIGNALS FROM THE SURROUNDING ECM, OUR RESULTS MAY PROVIDE INSIGHT INTO THE ETIOLOGY OF CHDS IN HUMANS, AND CAN BE APPLIED TO NOVEL TISSUE ENGINEERING THERAPIES AIMED AT RESTORING EFFICIENT HEART FUNCTION.

INFLUENCE OF EARLY LIFE PHYSICAL INACTIVITY DURING A KEY PERIOD OF POSTNATAL DEVELOPMENT ON ADULT MUSCLE QUALITY – FROM MATRIX TO MORTALITY - PROJECT SUMMARY THE PHYSICAL INACTIVITY (PIA) EPIDEMIC HAS FAR-REACHING NEGATIVE HEALTH IMPACTS ON ADULTS, BUT EVEN MORE SO ON CHILDREN, WHO ARE FACING MORE PIA THAN EVER IN DIVERSE FORMS. ALTHOUGH THE DETRIMENTAL IMPACTS OF PIA ON POSTNATAL MUSCLE ARE PRONOUNCED, AND THE NEGATIVE IMPACTS ON BONE ARE WELL ESTABLISHED ACROSS THE LIFECYCLE, THE IMPACT OF EARLY-LIFE PIA ON MUSCLE AND METABOLIC HEALTH IN ADULTHOOD IS NOT FULLY REALIZED. THUS, OUR OBJECTIVES ARE 1) TO INVESTIGATE THE EFFECT OF THE LEVEL OF EARLY-LIFE PHYSICAL INACTIVITY IN MICE ON THE MUSCLE QUALITY AND FUNCTION PHENOTYPE IN ADULTHOOD, 2) TO DETERMINE THE ROOT OF MUSCLE QUALITY LOSSES BY EXAMINING THE REGULATORY ASPECTS OF THE EXTRACELLULAR MATRIX (ECM) IN ADULTHOOD, 3) TO INVESTIGATE THE EFFECT OF THE LEVEL OF EARLY-LIFE PHYSICAL INACTIVITY ON FRAILTY DEVELOPMENT AND SURVIVAL AND 4) TO EXPOSE UNDERGRADUATE STUDENTS TO MERITORIOUS BIOMEDICAL RESEARCH METHODS. WE HAVE PILOTED EARLY-LIFE PIA EXPERIMENTS, PHYSICAL PERFORMANCE TESTS, IMMUNOFLUORESCENCE METHODS, AND DATA ANALYSIS WITH UNDERGRADUATE RESEARCHERS AND ARE PREPARED TO COMPLETE THIS PROPOSAL. WE HAVE PRELIMINARY DATA INDICATING THAT BRIEF (2WK) EARLY LIFE PIA IN MICE PRODUCES WEAKER MUSCLES, REDUCED MUSCLE QUALITY, INCREASED ECM, AND DECREASED MUSCLE MACROPHAGES 5 MONTHS LATER AS ADULTS. THIS EQUATES TO ABOUT HALF A YEAR OF PIA DURING THE FIRST FEW YEARS OF LIFE AND EARLY ADULTHOOD IS ABOUT 25-30Y OF AGE FOR A HUMAN. OUR PRELIMINARY DATA SUGGEST A CONCERNING TRAJECTORY POTENTIALLY CHARACTERIZED BY ATTENUATED MUSCLE QUALITY AND FUNCTION -- ALL OF WHICH ARE ASSOCIATED WITH PREMATURE AGING AND THE POSSIBILITY OF RAPID DEVELOPMENT OF FRAILTY AND REDUCED LIFESPAN. THUS, WE AIM TO CHARACTERIZE HOW THE LEVEL OF EARLY LIFE PIA, ROUGHLY EQUIVALENT TO ~6 MONTHS HUMAN CHILD, WILL CONTRIBUTE TO MUSCLE QUALITY (ECM CHANGES) AND PHYSICAL FUNCTION LOSSES RESULTING FROM BRIEF (2 WEEKS) EARLY LIFE PIA DURING A KEY PERIOD OF DEVELOPMENT IN EARLY ADULTHOOD (6 MO). THE EARLY LIFE PIA WILL BE CONDUCTED WITH THREE LEVELS OF INTENSITY WITH MUSCLE DISUSE, REDUCED ACTIVITY, AND SEDENTARY CAGE ACTIVITY COMPARED TO ACTIVE CONTROL WITH RUNNING WHEEL ACCESS. WE WILL EXAMINE SKELETAL MUSCLE ECM COLLAGEN CONTENT AND STRUCTURE, MUSCLE MACROPHAGES, AND ECM REGULATION IN ADULT MALE AND FEMALE MICE EXPOSED TO BRIEF EARLY-LIFE PIA. LASTLY, WE WILL USE PHYSICAL PERFORMANCE TESTING THROUGHOUT AGING TO EXAMINE THE EFFECT OF THE DEVELOPMENT OF FRAILTY AND SURVIVAL CURVES IN MICE EXPOSED TO BRIEF EARLY-LIFE PIA

COLLABORATIVE RESEARCH: MULTI-MUTUALIST EFFECTS ON POPULATIONS, COMMUNITIES, AND ECOSYSTEMS ACROSS ECOLOGICAL GRADIENTS

INFLUENCE OF AEROBIC TRAINING AND WEIGHT LOSS ON SKELETAL MUSCLE INFLAMMATORY MARKERS AND MUSCLE PROTEIN BALANCE IN OLDER ADULTS

PREDICTION ERROR IN CONTEXTUAL FEAR MEMORY RECONSOLIDATION

MISSING LINKS PROBLEMS AND PARTICIPATION IN COLLECTIVE DECISIONS

INFLAMMATION IS A DRIVER OF NEWT LENS REGENERATION - NEWTS ARE ONE OF THE CLOSEST LIVING RELATIVES TO MAMMALS THAT RETAIN FULL REGENERATIVE CAPABILITIES THROUGHOUT THEIR ENTIRE LIFETIME. EGUCHI ET AL., DEMONSTRATED THAT THE LENS OF THE NEWT COULD BE REPEATEDLY REMOVED 18 TIMES OVER THE COURSE OF 16 YEARS AND THE LAST LENS REGENERATED AS PERFECTLY AS THE FIRST. THIS ABILITY IN NEWTS IS REMARKABLE CONSIDERING THAT HUMANS HAVE A HIGH RISK OF DEVELOPING POSTERIOR CAPSULE OPACIFICATION AFTER A SINGLE CATARACT SURGERY. AS A RESULT, WE THOUGHT FOR DECADES THAT NEWTS WERE IMPERVIOUS TO FIBROTIC DISEASE. HOWEVER, OUR PRELIMINARY DATA DEMONSTRATES MACROPHAGE DEPLETION NOT ONLY PREVENTED LENS REGENERATION BUT IT ALSO INDUCED A FIBROTIC-LIKE RESPONSE AFTER A SINGLE INJURY IN THE NEWT EYE. WE ALSO FOUND THAT TREATMENT WITH THE ANTI-INFLAMMATORY DRUG DEXAMETHASONE PREVENTED LENS REGENERATION BUT FAILED TO INDUCE A FIBROTIC RESPONSE TO INJURY. THIS HIGHLIGHTS A TRULY UNIQUE ROLE OF THE NEWT MACROPHAGE IN PREVENTING FIBROTIC DISEASE. IT ALSO SUGGESTS THAT WHILE INFLAMMATION AND MACROPHAGES ARE NECESSARY FOR REGENERATION IN THE NEWT, THEY HAVE UNIQUE FUNCTIONS. BASED ON OUR PRELIMINARY DATA AND WORK DONE IN ZEBRAFISH, OUR HYPOTHESIS IS THAT INFLAMMATION IS REQUIRED TO TRIGGER IRIS PIGMENTED EPITHELIAL (IPE) CELL REPROGRAMMING AND THAT MACROPHAGES PLACE LIMITS ON THE INFLAMMATORY POTENTIAL OF THE INJURY SITE. THEREBY THE ABSENCE OF MACROPHAGES WOULD BE ASSOCIATED WITH A FIBROTIC RESPONSE TO INJURY RESULTING FROM UNCONTROLLED INFLAMMATION TRIGGERING THE RECRUITMENT AND DIFFERENTIATION OF MYOFIBROBLASTS AND ABERRANT EXTRACELLULAR MATRIX DEPOSITION. TO TEST THESE HYPOTHESES, WE WILL CHARACTERIZE THE MAGNITUDE AND DURATION OF THE INFLAMMATORY RESPONSE IN THE NEWT EYE, THE IMPACT OF DEXAMETHASONE AND MACROPHAGE DEPLETION ON IPE CELL APOPTOSIS, PROLIFERATION, AND MARKERS OF IPE CELL REPROGRAMMING. WE WILL ALSO CHARACTERIZE MACROPHAGE POLARIZATION STATES AND THEIR TRANSITION FROM M1 TO M2 PHENOTYPES DURING THE INFLAMMATORY RESPONSE. FINALLY, THE TYPE OF FIBROTIC INJURY INDUCED BY MACROPHAGE DEPLETION WILL BE FURTHER CHARACTERIZED AS WELL AS POSSIBLE MECHANISMS LEADING TO ITS FORMATION. RECENT WORK IN MICE AND HUMANS HAS DEMONSTRATED AN INHERENT PLASTICITY IN MACROPHAGE FUNCTION SINCE THEY ARE HIGHLY PROGRAMMABLE THROUGH MANIPULATION OF THEIR LOCAL MICROENVIRONMENT. OUR LONG TERM GOAL IS TO CHARACTERIZE FACTORS IN THE NEWT MICROENVIRONMENT THAT INSTRUCT AN ANTI-FIBROTIC RESPONSE FROM NEWT MACROPHAGES THAT COULD BE CAPABLE OF ELICITING SIMILAR FUNCTIONS IN HUMAN MACROPHAGES AS A TREATMENT OR PREVENTION STRATEGY FOR FIBROTIC DISEASES.

REGULATION OF THE LENS TRANSCRIPTOME AND CHROMATIN ARCHITECTURE BY FOXE3 - REVELATION OF NOVEL MOLECULAR MECHANISMS THAT REGULATE TRANSCRIPTIONAL NETWORKS CONTROLLING CELLULAR DIFFERENTIATION PROVIDES ESSENTIAL INFORMATION RELEVANT BOTH TO UNDERSTANDING ORGANOGENESIS AND FOR REPROGRAMMING CELLS FOR REGENERATIVE THERAPIES. THE OCULAR LENS PROVIDES A SIMPLE, SELF-CONTAINED TISSUE WITH CHARACTERISTIC PATTERNS OF DIFFERENTIATION-SPECIFIC GENE EXPRESSION TO MODEL HOW TRANSCRIPTION FACTORS REGULATE CHROMATIN LANDSCAPES TO DIRECT SPECIFIC TRANSCRIPTIONAL NETWORKS THROUGH COOPERATIVE INTERACTIONS WITH ENHANCERS, PROMOTERS, AND OTHER REGULATORY PROTEIN COMPLEXES. THE FORKHEAD TRANSCRIPTION FACTOR, FOXE3, IS AN ABUNDANT TRANSCRIPTION FACTOR EXPRESSED IN THE EARLY LENS FORMING ECTODERM, AND MAINTAINED IN THE LENS EPITHELIUM, DOWNSTREAM OF PAX6 EXPRESSION. IN FACT, MUTATIONS IN FOXE3 MIRROR MANY OF THE OCULAR PHENOTYPES (PETERS ANOMALY, CATARACTS, REDUCED EPITHELIA PROLIFERATION AND FIBER CELL DIFFERENTIATION) RESULTING FROM DEFICIENCIES IN PAX6 OR AP-2, THE TWO OTHER ABUNDANTLY EXPRESSED TRANSCRIPTION FACTORS IN LENS EPITHELIUM. HOWEVER, LITTLE INFORMATION EXISTS CONCERNING HOW FOXE3 REGULATES LENS DEVELOPMENT. AN RNA-SEQ ANALYSIS IN LENSES FROM A NEWLY CREATED FOXE3 ALLELE IDENTIFIED NUMEROUS DIFFERENTIALLY REGULATED GENES. THESE INCLUDED DOWNREGULATION OF MANY CLASSICAL LENS IDENTITY GENES (INCLUDING BFSP1, BFSP2, DNASE2B AND MULTIPLE CRYSTALLINS) AND UPREGULATION OF MANY GENES ASSOCIATED WITH NEURAL AND OR RETINA DIFFERENTIATION (INCLUDING NR2E1, OTX2, ASCL1, TBX3, RAX, VSX2, LHX2 AND SIX6). THIS SURPRISING SHIFT IN GENE EXPRESSION IN FOXE3 DEFICIENT LENSES, COUPLED WITH THE STRUCTURAL SIMILARITY OF FOXE3 TO SEVERAL PIONEER TRANSCRIPTION FACTORS THAT CAN ACT AS KEY DRIVERS OF CELLULAR DIFFERENTIATION AND REPROGRAMMING, LED TO THE HYPOTHESIS THAT TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION IN LENS MEDIATED BY FOXE3 IS DETERMINED BY ITS DYNAMIC INTERACTIONS WITH CHROMATIN RESULTING IN ITS PRESENCE IN BOTH OPEN AND CLOSED CHROMATIN THROUGH CLUSTER OF ADJACENT CIS-REGULATORY SITES AND TRANS- ACTING DNA-BINDING TRANSCRIPTION FACTORS IN THE PROMOTERS AND ENHANCERS. TWO SPECIFIC AIMS WILL TEST THIS HYPOTHESIS. 1) TO DETERMINE HOW THE LOSS OF FOXE3 FUNCTION AFFECTS CHROMATIN LANDSCAPE AND GENE CONTROL IN THE LENS, COMBINATIONS OF ATAC-SEQ, SCRNA-SEQ AND BULK RNA-SEQ WILL BE EMPLOYED ON FOXE3 NULL LENSES. 2) TO DETERMINE THE CIS-REGULATORY GRAMMAR OF FOXE3-BOUND PROMOTERS AND ENHANCERS IN LENS, FOXE3 BINDING SITES IN LENS CHROMATIN WILL BE DISCOVERED USING CUT&RUN FOLLOWED BY BIOINFORMATIC ANALYSIS TO IDENTIFY THE CONSENSUS FOXE3 BINDING MOTIF AND ADJACENT TRANSCRIPTION FACTOR BINDING MOTIFS. THIS INFORMATION WILL BE INTEGRATED TO DISCOVER DIRECT FOXE3 TRANSCRIPTIONAL TARGETS, WHICH WILL BE VALIDATED BY RT-QPCR AND LUCIFERASE ASSAYS. THE FUNDAMENTAL INFORMATION GAINED BY THESE APPROACHES WILL FUEL BROADER AND SYSTEMATIC ANALYSIS OF MOLECULAR MECHANISMS OF GENE CONTROL BY FOX TRANSCRIPTION FACTORS FOCUSED ON THEIR IMPACT ON CHROMATIN STRUCTURAL DYNAMICS FOR TISSUE DIFFERENTIATION AND CELLULAR REPROGRAMMING.

NEW START GRANT

RESEARCH EXPERIENCES FOR UNDERGRADUATES SITE: ECOLOGY IN HUMAN-DOMINATED LANDSCAPES

UTILIZING THE CHICKEN EMBRYO TO DECODE THE TRANSCRIPTIONAL REGULATION OF FOXE3 - THE DISCOVERY OF PRECISELY HOW TRANSCRIPTION FACTORS (TFS) FUNCTION TO REGULATE TRANSCRIPTIONAL PROGRAMS DURING DEVELOPMENT IS OF FUNDAMENTAL IMPORTANCE FOR UNDERSTANDING CELLULAR IDENTITY AND ORGANOGENESIS. THE STEREOTYPICAL ARCHITECTURE, ANATOMICAL SIMPLICITY AND WEALTH OF PREVIOUS DEVELOPMENTAL INFORMATION MAKES THE LENS A PARTICULARLY ATTRACTIVE TISSUE IN WHICH TO TEASE OUT THESE DISCOVERIES. THE ADVENT OF GENOME-WIDE SEQUENCING STRATEGIES TO IDENTIFY THE EPIGENETIC STATE OF CHROMATIN WITHIN SPECIFIC CELL TYPES HAS MADE IT POSSIBLE TO IDENTIFY CIS-REGULATORY ELEMENTS (CRES) THAT CONTROL GENE EXPRESSION WITHIN THESE CELLS. USING THESE STRATEGIES, CRES THAT PUTATIVELY REGULATE THE LENS TF GENE, FOXE3 HAVE BEEN DISCOVERED IN THE MOUSE GENOME. THE EXPRESSION OF FOXE3 IS LARGELY RESTRICTED TO THE LENS AND HOMOZYGOUS LOSS OF FUNCTION MUTATIONS RESULT IN APHAKIA AND/OR MICROPHTHALMIA IN ALL VERTEBRATE SPECIES WHERE THESE MUTATIONS HAVE BEEN IDENTIFIED, INCLUDING HUMANS. AS SUCH, FOXE3 REPRESENTS AN ATTRACTIVE TARGET TO ELUCIDATE HOW TFS UTILIZE CIS-REGULATORY ELEMENTS TO ACHIEVE TISSUE-SPECIFIC GENE EXPRESSION. FURTHERMORE, WHILE STUDIES IN MICE HAVE IDENTIFIED FOXE3 CRES THAT CONTAIN SPECIFIC TF MOTIFS AND BIND TO SPECIFIC TFS, TO DATE THE RELATIVE IMPORTANCE OF ANY OF THESE IDENTIFIED MOTIFS IN REGULATING FOXE3 EXPRESSION IN VIVO IS LACKING. THE CURRENT PROPOSAL SEEKS TO EXPLOIT THE DEVELOPMENTAL ADVANTAGES OF THE CHICK LENS TO DECODE THE CIS-REGULATORY GRAMMAR THAT DICTATES FOXE3 EXPRESSION IN BOTH THE CHICK AND MOUSE LENS. BUILDING ON RECENT INFORMATION THAT UNCOVERED GENOME WIDE CHROMATIN ACCESSIBILITY AND THE EPIGENETIC ACTIVE ENHANCER MODIFICATION (H3K27AC) FOUR PUTATIVE FOXE3 CRES HAVE BEEN IDENTIFIED IN THE CHICK GENOME. THIS PROPOSAL WILL ANNOTATE THE MOUSE AND CHICK FOXE3 CRES FOR THE PRESENCE OF KNOWN TF BINDING MOTIFS. THE PROPOSAL SEEKS TO EMPLOY RECOMBINANT RETROVIRAL VECTORS TO FUNCTIONALLY TEST THE REQUIREMENTS OF THESE CRES TO DRIVE REPORTER GENE EXPRESSION IN THE CHICK LENS. THE PROPOSAL WILL UTILIZE RETROVIRAL REPORTER CONSTRUCTS TO DETERMINE IF SPECIFIC TF MOTIFS, DISCOVERED WITHIN ESSENTIAL FOXE3 CRES, ARE ESSENTIAL TO DRIVE LENS-SPECIFIC EXPRESSION. IN ADDITION, A LENS-SPECIFIC CRISPR BASED GENOME EDITING STRATEGY WILL BE DEVELOPED IN THE CHICK LENS TO SCREEN CANDIDATE TFS FOR THEIR REQUIREMENT TO DRIVE THE NORMAL EXPRESSION PATTERN OF THE ENDOGENOUS FOXE3 GENE IN DEVELOPING CHICK LENSES. THE CENTRAL HYPOTHESIS TESTED IN THIS PROPOSAL IS THAT REGIONS OF NON-CODING OPEN CHROMATIN NEAR THE FOXE3 GENE IN BOTH MICE AND CHICKENS COMPRISE PROMOTER AND/OR ENHANCER ELEMENTS THAT INTERACT WITH TFS SUFFICIENT TO SPECIFICALLY DRIVE GENE EXPRESSION TO THE DEVELOPING CHICK LENS. THE SUCCESS OF THIS PROPOSAL WILL NOT ONLY DIRECTLY TEST THE ROLE OF SPECIFIC CRES AND TFS FOR THEIR ROLE IN REGULATING FOXE3 EXPRESSION IN VIVO BUT IT ALSO PROMISES TO ENHANCE THE UTILITY OF THE CHICK LENS FOR SCREENING GENE AND ENHANCER FUNCTION BY DEVELOPING CRISPR-BASED GENOME EDITING STRATEGIES.

INVESTIGATING THE ROLE OF NKX6-1 IN SECONDARY LENS FIBER CELL DIFFERENTIATION

DETERMINING THE ROLE OF DNA METHYLATION IN THE TISSUE-SPECIFIC EXPRESSION OF THE NA,K-ATPASE-NA/H EXCHANGER PH REGULATORY SYSTEM GENES. - ABSTRACT: EPIGENETIC MECHANISMS ARE CRITICAL FOR THE REGULATION OF TISSUE-SPECIFIC GENE EXPRESSION AND THEREFORE THE DEVELOPMENT AND FUNCTION OF ALL TISSUES INCLUDING THE MALE GERM LINE. DNA METHYLATION, AN IMPORTANT EPIGENETIC MECHANISM, HAS BEEN IMPLICATED IN THE REGULATION OF EXPRESSION OF SEVERAL TESTIS/SPERM-SPECIFIC GENES. FURTHERMORE, ABNORMAL DNA METHYLATION IN SPERM HAS BEEN ASSOCIATED WITH INFERTILITY IN MALES. HOWEVER, LITTLE PROGRESS HAS BEEN MADE IN DETERMINING A CAUSAL RELATIONSHIP AND FUNCTIONAL SIGNIFICANCE OF METHYLATION OF INDIVIDUAL CPG DINUCLEOTIDES AND RESULTING GENE ACTIVITY, LIMITING THE FIELD OF EPIGENETICS. IN THE STUDIES PROPOSED HERE, WE WILL EXAMINE THE ROLE THAT DNA METHYLATION/DEMETHYLATION PLAYS IN REGULATING THE TISSUE-SPECIFIC GENE EXPRESSION OF A GROUP OF FUNCTIONALLY RELATED NA+-TRANSPORTING MEMBRANE PROTEINS, THE NA,K-ATPASE AND NA/H EXCHANGERS (NHES), THAT ARE IMPORTANT IN SPERM PHYSIOLOGY AND MALE FERTILITY. THE NA,K-ATPASE ESTABLISHES THE NA+ GRADIENT ACROSS THE PLASMA MEMBRANE THAT PROVIDES THE ENERGY FOR THE NHES TO EXPORT H+ FROM THE CELL AND REGULATE INTRACELLULAR PH. ONE NA,K-ATPASE ALPHA SUBUNIT (ALPHA4) AND THREE NHES (NHA1/NHEDC1, NHA2/NHEDC2, AND NHE10) PLAY IMPORTANT ROLES IN SPERM AS LOSS OF THESE TRANSPORTERS RESULTS IN INFERTILE MALE MICE. THE NA,K-ATPASE ALPHA4 ISOFORM AND THREE NHES (NHA1/NHEDC1, NHE10, AND NHE11) ARE EXPRESSED ONLY IN THE TESTIS/SPERM SUGGESTING THAT THESE TRANSPORTERS COMPRISE A TESTIS/SPERM-SPECIFIC NA,K-ATPASE/NHE FUNCTIONAL NETWORK TO REGULATE INTRACELLULAR PH AND SPERM FUNCTION. USING BIOINFORMATICS, REPORTER GENE ASSAYS, AND TARGETED METHYLATION/DEMETHYLATION, WE WILL EXPLORE THE ROLE THAT METHYLATION PLAYS IN THE EXPRESSION OF THE TESTIS/SPERM-SPECIFIC NA,K-ATPASE/NHE FUNCTIONAL NETWORK GENES AND WILL IDENTIFY THE SPECIFIC CPGS IN EACH GENE WHICH MEDIATE TISSUE-SPECIFIC EXPRESSION. BOTH ABNORMAL DNA METHYLATION OF IMPRINTED AND NON-IMPRINTED GENES AND REDUCED EXPRESSION OF THE NA,K-ATPASE ALPHA4 SUBUNIT AND NHE10 HAVE BEEN FOUND TO BE ASSOCIATED WITH INFERTILE HUMAN MALES. THEREFORE, BEYOND PROVIDING FUNDAMENTAL INFORMATION ABOUT DNA METHYLATION-DEPENDENT GENE EXPRESSION, UNDERSTANDING THE DNA METHYLATION-DEPENDENT REGULATION OF THE EXPRESSION OF THE TESTIS/SPERM-SPECIFIC NA,K-ATPASE/NHE FUNCTIONAL NETWORK GENES COULD IMPACT OUR UNDERSTANDING OF HUMAN REPRODUCTIVE BIOLOGY AND AFFECT ITS TREATMENT IN THE FUTURE - IDENTIFICATION OF THE SPECIFIC ELEMENTS THAT REGULATE EXPRESSION OF THESE GENES, WILL PROVIDE THE EPIGENETIC ROADMAP TO ALLOW FOR THE TARGETED UPREGULATION OF THESE GENES IN MALES WHO ARE INFERTILE DUE TO LOSS OF THEIR EXPRESSION.

COLLABORATIVE RESEARCH: WINTER SURVIVAL MECHANISMS AND ADAPTIVE GENETIC VARIATION IN AN ANTARCTIC INSECT

INVESTIGATING MEMBRANE PROTEINS WITH MAGNETIC RESONANCE SPECTROSCOPY

REAP UNDERUTILIZED TECHNOLOGY 24/31

INTEGRATED PARAMAGNETIC RESONANCE OF HIGH-SPIN CO(II) SYSTEMS

RETINAL PIGMENTED EPITHELIUM REPROGRAMMING AND RETINA REGENERATION

IN VIVO IMAGING OF NEWT LENS REGENERATION: NOVEL MOLECULAR, CELLULAR AND FUNCTIONAL INSIGHTS

O-PHENYLENES: CONTROLLED FOLDING AND DIRECTED OXIDATIVE PLANARIZATION

EPIGENETIC REGULATION OF LENS FIBER CELL DIFFERENTIATION: THE ROLE OF DNA METHYLA

HIERARCHICAL COMPOSITE CONSTRUCTS AS TISSUE ENGINEERING SCAFFOLDS

EARMARKS

CHILD CARE ACCESS MEANS PARENTS IN SCHOOL PROGRAM

RUI: PATTERNS OF BIODIVERSITY OF BENTHIC INVERTEBRATES IN CHIHUAHUAN DESERT SPRINGS

ANALYSIS OF SUBCORTICAL NETWORKS THAT PROMOTE AVERSION-RESISTANT ALCOHOL DRINKING

CHOLINERGIC INTERNEURON REGULATION OF OPIOID-RELATED BEHAVIORS - PROJECT SUMMARY OPIOID USE DISORDER (OUD) IS A DEBILITATING AND LIFE-LONG ADDICTIVE DISEASE WITH SIGNIFICANT PUBLIC HEALTH COSTS. OUD IS CHARACTERIZED BY VARIOUS SYMPTOMS, INCLUDING A COMPULSIVE NEED TO USE, LOSS OF CONTROL OVER USE, AND A NEGATIVE EMOTIONAL STATE INDUCED BY WITHDRAWAL. MU-OPIOID RECEPTORS (MORS) IN THE VENTRAL TEGMENTAL AREA (VTA) ARE KNOWN TO CONTRIBUTE TO BOTH THE REWARDING EFFECTS OF OPIOID USE AND THE AVERSIVE SIGNS AND SYMPTOMS OF OPIOID WITHDRAWAL. HOWEVER, THERE IS GROWING EVIDENCE THAT ADDITIONAL POPULATIONS OF MOR, WHICH IS BROADLY EXPRESSED THROUGHOUT EMOTIONAL AND MOTIVATIONAL BRAIN CIRCUITS, CRITICALLY CONTRIBUTE TO OPIOID-RELATED BEHAVIORS. STRIATAL CHOLINERGIC INTERNEURONS (CINS) REGULATE DOPAMINE RELEASE AND RESPONDING FOR REWARDS. GIVEN THESE IMPORTANT FUNCTIONS OF CINS, AND BECAUSE THIS NEURONAL SUBPOPULATION EXPRESSES MOR, WE HYPOTHESIZE THAT MOR STIMULATION ALTERS CIN ACTIVITY AND STRIATAL DOPAMINE RELEASE TO PROMOTE OPIOID REWARD, CONSUMPTION, AND WITHDRAWAL-INDUCED AVERSION. OUR EXPERIMENTS WILL TEST THIS HYPOTHESIS THROUGH COMPLETION OF TWO PRIMARY SPECIFIC AIMS. WE WILL DETERMINE 1) WHETHER MORS ON CHOLINERGIC INTERNEURONS PARTICIPATE IN OPIOID REWARD AND WITHDRAWAL AND 2) WHETHER CIN MORS REGULATE DOPAMINE RELEASE DURING OPIOID REWARD AND WITHDRAWAL. OPIOID REWARD WILL BE TESTED USING A CONDITIONED PLACE PREFERENCE (CPP) TASK AND WITHDRAWAL USING CONDITIONED PLACE AVERSION (CPA). OPIOID CONSUMPTION WILL BE ASSESSED WITH A LIMITED ACCESS, TWO-BOTTLE CHOICE FENTANYL DRINKING TASK DEVELOPED IN OUR LAB. COLLECTIVELY, COMPLETION OF THESE AIMS WILL DEMONSTRATE THAT MORS ON NAC CINS CONTRIBUTE TO OPIOID REWARD, CONSUMPTION, AND WITHDRAWAL THROUGH MODULATION OF DA RELEASE. FURTHERMORE, WE WILL TRAIN UNDERGRADUATE STUDENTS IN A BROAD ARRAY OF MODERN BEHAVIORAL NEUROSCIENCE TECHNIQUES, SUCH AS CHEMOGENETICS, FLUORESCENT IN SITU HYBRIDIZATION, AND FLUOROPHOTOMETRY. THESE ACTIVITIES WILL EXPAND ACCESS TO MEANINGFUL RESEARCH OPPORTUNITIES TO A DIVERSE SET OF TALENTED UNDERGRADUATE STUDENTS INTERESTED IN NEUROSCIENCE AND OTHER BIOMEDICAL RESEARCH FIELDS AT MIAMI UNIVERSITY.

PHYSIOLOGICAL MECHANISMS IN ANURAN ADAPTATION TO EXTREME COLD

COLLABORATIVE RESEARCH: AMMONIA OXIDIZERS AND THEIR HETEROTROPHIC FRIENDS

CBM: A NOVEL INTERVENTION FOR ALCOHOL DEPENDENCE AND SOCIAL ANXIETY

PRELIMINARY INVESTIGATION OF A SOCIAL COGNITIVE INTERVENTION IN EARLY COURSES

VELOCITY-SORTING AND STOCHASTIC RESONANCES IN COLD ATOM OPTICAL LATTICES PATH TOWARD EFFICIENT NANO-DEVICES

A WEB TUTOR TO HELP WOMEN DECIDE ABOUT TESTING FOR GENETIC BREAST CANCER RISK

CHS: SMALL: REALISTIC NAVIGATION IN THE THIRD DIMENSION USING LOW COST, PORTABLE, WEARABLE IMMERSIVE ENVIRONMENT SYSTEMS

SEX-SPECIFIC EFFECTS OF INFANT TRAUMA ON ADULT ALCOHOL DRINKING: ROLE OF AMYGDALA INTERCALATED NEURONS - PROJECT SUMMARY CHILDHOOD TRAUMA CONFERS VULNERABILITY TO COMORBID PTSD/AUD, PARTICULARLY IN FEMALE PATIENTS. BECAUSE THE NEURAL SUBSTRATES MEDIATING VULNERABILITY TO PTSD AND AUD MAY BE SIMILAR, ELUCIDATING THESE COMMON MECHANISMS MAY PROVIDE THE FOUNDATION FOR NOVEL TREATMENT OPTIONS FOR BOTH. INFANT TRAUMA IS A POWERFUL, CONSTRUCT-VALID MODEL OF PTSD AND AUD. TRAUMA-EXPOSED ANIMALS SHOW POTENTIATED FEAR LEARNING, RESISTANCE TO EXTINCTION, AND INCREASED ALCOHOL DRINKING AS ADULTS AND THERE IS AN ENHANCED VULNERABILITY TO THESE EFFECTS IN FEMALES. THIS PROPOSAL EXPLORES THE NOVEL HYPOTHESIS THAT INFANT TRAUMA PRODUCES ENDURING UPREGULATION IN MOR EXPRESSION IN AMYGDALA INTERCALATED NEURONS, ULTIMATELY DISINHIBITING NEURONS OF THE CENTRAL AMYGDALA. OUR EXPERIMENTS WILL TEST THIS HYPOTHESIS THROUGH COMPLETION OF THREE PRIMARY SPECIFIC AIMS. IN MALE AND FEMALE MICE, WE WILL 1) DETERMINE WHETHER MOR MRNA EXPRESSION IS INCREASED IN AMYGDALA INTERCALATED NEURONS FOLLOWING INFANT TRAUMA 2) IDENTIFY NOVEL MOLECULAR TARGETS IN THE ITC THAT ARE REGULATED BY STRESS AND ALCOHOL, AND 3) DEMONSTRATE A CAUSAL ROLE FOR INTERCALATED CELLS MORS IN MEDIATING THE EFFECTS OF INFANT TRAUMA ON ALCOHOL DRINKING. INFANT TRAUMA WILL BE MODELED BY DELIVERING 15 FOOTSHOCKS ON POSTNATAL DAY 17. ALCOHOL DRINKING WILL BE ASSESSED IN A TWO-BOTTLE CHOICE, DRINKING IN THE DARK PARADIGM. COLLECTIVELY, COMPLETION OF THESE AIMS WILL PROVIDE SUPPORT FOR A MECHANISM BY WHICH EARLY LIFE ADVERSITY MAY INCREASE SENSITIVITY TO STRESSORS AND INCREASE DRINKING IN ADULTHOOD. OUR WORK WILL ALSO FURTHER VALIDATE A MODEL OF TRAUMATIC STRESS AND SEX- DEPENDENT EFFECTS ON ALCOHOL DRINKING.

COLLABORATIVE RESEARCH: BIOAVAILABILITY OF MINERAL-ASSOCIATED MOLYBDENUM AS A COFACTOR OF NIF NITROGENASE FOR N2 FIXATION

NEUROMODULATORY CONTROL OF SWITCHING BETWEEN SINGLE AND DUAL OSCILLATORY NETWORK STATES

ACINETOBACTER BAUMANNII GENE REGULATION IN RESPONSE TO ILLUMINATION

DOES PROXIMITY OF HYDRAULIC FRACTURING AND WASTEWATER DISPOSAL TO BASEMENT INCREASE THE LIKELIHOOD OF INDUCED SEISMICITY IN THE CENTRAL AND EASTERN U

REU SITE: PHYSICS AT MIAMI UNIVERSITY

GLIAL REMODELING IN DROSOPHILA: PROLIFERATION, MEMBRANE OUTGROWTH AND NERVE ENSHE

FSML: A REGIONAL HUB FOR THE EON'S AT LACAWAC SANCTUARY

COLLABORATIVE RESEARCH: ORIGIN AND EVOLUTION OF INTRAPLATE MAGMATISM AT THE REVILLAGIGEDO ARCHIPELAGO, MEXICO

COLLABORATIVE RESEARCH: VOLCANISM ON THE EDGE - BASALTIC VOLCANISM FROM SOURCE TO SURFACE ACROSS THE COLORADO PLATEAU/BASIN & RANGE TRANSITION IN SW UTAH -THE AMERICAN SOUTHWEST IS HOME TO NEARLY FORTY BASALTIC VOLCANIC FIELDS THAT COLLECTIVELY CONTAIN MORE THAN 2,000 QUATERNARY VOLCANOES, INCLUDING MANY THAT HAVE ERUPTED RELATIVELY RECENTLY (PAST 50,000 YEARS). MOST OF THESE VOLCANOES ARE CONSIDERED TO BE ?MONOGENETIC? (I.E., THEY ERUPT ONLY ONCE), AND THEY GENERALLY PRODUCE RELATIVELY SMALL VOLUME ERUPTIONS (<1 KM3). NEVERTHELESS, IT HAS RECENTLY BECOME CLEAR THAT SUCH ERUPTIONS CAN POSE SIGNIFICANT HAZARDS DUE TO THEIR WIDE VARIETY OF ERUPTIVE STYLES, INCLUDING EXPLOSIVE BEHAVIOR, AND THE FACT THAT THE LOCATION OF ANY FUTURE ERUPTION IS UNKNOWN. IN THE SOUTHWEST US, NEITHER THE CAUSE OF THIS VOLCANISM NOR THE FREQUENCY OF RECENT ERUPTIONS IS WELL UNDERSTOOD. THIS PROJECT WILL FOCUS ON VOLCANISM IN SW UTAH, IN THE TRANSITION BETWEEN THE COLORADO PLATEAU AND THE BASIN AND RANGE PROVINCES, AN AREA THAT IS PARTICULARLY ENIGMATIC WITH REGARD TO THE CAUSES OF VOLCANISM, AND POORLY CONSTRAINED WITH REGARD TO THE NATURE AND FREQUENCY OF RECENT VOLCANIC ACTIVITY. BY INTEGRATING DETAILED FIELD OBSERVATIONS AND MAPPING, RADIOMETRIC DATING, PHYSICAL VOLCANOLOGY, AND GEOCHEMICAL ANALYSES, THIS PROJECT WILL PROVIDE KEY CONSTRAINTS ON THE SOURCES, PROCESSES, AND TIMESCALES OF MAGMA ASCENT AND STORAGE LEADING TO ERUPTION, AND THE LINK TO ERUPTIVE STYLE AND HAZARDS. IN ADDITION TO PROVIDING INFORMATION ABOUT HAZARDS TO THE PUBLIC, THIS WORK INCLUDES MENTORING AND TRAINING OF TWO PHD STUDENTS AND SEVERAL UNDERGRADUATE RESEARCHERS IN FIELD, ANALYTICAL AND IMAGING TECHNIQUES. PIS WILL ALSO ENGAGE IN A VARIETY OF OUTREACH ACTIVITIES RELATED TO THE PROJECT, INCLUDING RESEARCH-BASED EDUCATIONAL ACTIVITIES FOR K-12 STUDENTS AND TEACHERS, PUBLIC TALKS, AND A SUMMER COURSE FOR MIDDLE AND HIGH SCHOOL STUDENTS. THE SOUTHWEST US CONTAINS AT LEAST 2229 QUATERNARY VOLCANOES, MOST OF WHICH ARE MONOGENETIC. SIGNIFICANT QUESTIONS SURROUND THE CAUSES AND SOURCES OF THE VOLCANISM, THE AGES AND ERUPTIVE RECURRENCE INTERVALS, AND THE RANGE OF ? AND CONTROLS ON ? ERUPTIVE STYLES. UNDERSTANDING THE PROCESSES THAT GOVERN MONOGENETIC VOLCANISM IN THE SOUTHWEST US, AND THE TIME SCALES OVER WHICH THESE PROCESSES OPERATE, IS CRITICAL FOR HAZARD AND RISK ASSESSMENT. IN ADDITION, THE MAFIC NATURE OF MANY OF THESE MONOGENETIC VOLCANIC FIELDS MAKES THEM IDEAL AS PROBES OF THE MANTLE SOURCES THAT THEY TAP, AND SPATIAL-TEMPORAL-COMPOSITIONAL VARIATIONS CAN THUS PROVIDE A UNIQUE RECORD OF THE COMPLEX TECTONIC HISTORY IN THIS AREA. WE PROPOSE AN INTEGRATED PHYSICAL VOLCANOLOGY AND PETROLOGY/GEOCHEMISTRY STUDY OF QUATERNARY VOLCANISM IN THE SW UTAH VOLCANIC FIELD, SPANNING THE TRANSITION FROM THE BASIN AND RANGE TO THE COLORADO PLATEAU, TO ELUCIDATE LINKS BETWEEN TECTONICS, MAGMA SOURCES, AND ERUPTIVE STYLES AND HAZARDS. PRIMARY OBJECTIVES INCLUDE: 1) ESTABLISHING AGE RANGES AND SYSTEMATIC AGE PROGRESSIONS, IF EXTANT; 2) EVALUATING THE RANGE OF ERUPTIVE STYLES AND ASSOCIATED HAZARDS; 3) DETERMINING POTENTIAL RELATIONSHIPS OF ERUPTIVE ACTIVITY TO LOCAL TECTONIC FEATURES; 4) CONSTRAINING THE NATURE (LITHOSPHERIC VS. ASTHENOSPHERIC), LOCATION (DEPTH), AND SPATIAL HETEROGENEITY OF THE MANTLE SOURCES TAPPED IN THE ERUPTIONS; 5) ASSESSING THE RELATIVE IMPORTANCE OF MANTLE VERSUS CRUSTAL CONTROL ON MAGMA COMPOSITION AND ERUPTIVE STYLE, AND THE INFLUENCE OF MAGMATIC WATER CONTENT; AND 6) CONSTRAINING TIMESCALES AND THE IMPORTANCE OF MAGMA STORAGE SYSTEMS IN ASCENT FROM SOURCE TO SURFACE. OUR INTEGRATED APPROACH WILL INVOLVE DETAILED FIELD MAPPING, 40AR/39AR DATING, TEXTURAL ANALYSIS OF ERUPTIVE PRODUCTS, AND ELEMENTAL AND ISOTOPIC ANALYSES AT BOTH THE WHOLE-ROCK AND MINERAL SCALES. 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.

CAPACITY BUILDING FOR THE NATIONAL BREATH OF LIFE NATIVE AMERICAN PHILOLOGY MODEL

TSC1 REGULATION OF PURKINJE NEURON FIRING AND CEREBELLAR FUNCTION - AUTISM SPECTRUM DISORDER (ASD) IS A PREVALENT NEURODEVELOPMENTAL DISORDER THAT AFFECTS AN ESTIMATED 1 IN 59 INDIVIDUALS. ASD DIAGNOSES INVOLVE A RANGE AND OFTEN HETEROGENOUS ASSORTMENT OF SYMPTOMS, WHICH INCLUDE IMPAIRED SOCIAL INTERACTIONS, MOTOR COORDINATION, COMMUNICATION ABILITY, AND VOCALIZATIONS, AS WELL AS EXAGGERATED REPETITIVE MOVEMENTS. OUR UNDERSTANDING, HOWEVER, OF THE MOLECULAR, CELLULAR, AND NEURAL CIRCUIT DYSFUNCTION THAT DRIVES ASD-LINKED BEHAVIORS REMAINS UNCLEAR. ANOTHER NEURODEVELOPMENTAL DISORDER, TUBEROUS SCLEROSIS, IS CAUSED BY LOSS OF FUNCTION MUTATIONS IN TUBEROUS SCLEROSIS 1 OR 2 (TSC1, TSC2). INTERESTINGLY, >50% OF INDIVIDUALS WITH TSC ARE ALSO DIAGNOSED WITH ASD, MAKING TSC MUTATIONS ONE OF THE MOST PREVALENT MONOGENETIC CAUSES OF ASD. IN MICE, THE SELECTIVE DELETION OF ONE OR TWO TSC1 ALLELES SELECTIVELY IN CEREBELLAR PURKINJE NEURONS (PCP2:TSC1+/-, PCP2:TSC1-/-) RESULTS IN MULTIPLE AUTISTIC-LIKE BEHAVIORS. WITH THIS ANIMAL MODEL, WE CAN CONNECT THE DYSFUNCTION OF A SINGLE NEURONAL CELL TYPE, PURKINJE NEURONS IN THE CEREBELLUM, WITH AUTISTIC-LIKE BEHAVIORS. INITIAL STUDIES USING PCP2:TSC1 MICE REVEALED THAT PURKINJE NEURONS LACKING TSC1 EXPRESSION FIRE AT LOWER RATES THAN WILD TYPE PURKINJE NEURONS. IN THE FOLLOWING AIMS, WE WILL EXTEND THESE STUDIES BY (1) DEFINING THE MOLECULAR AND BIOPHYSICAL CHANGES THAT CAUSE REDUCED FIRING RATES IN PCP2:TSC1+/- AND PCP2:TSC1-/- PURKINJE NEURONS, AND (2) DETERMINE HOW THE REDUCED FIRING RATES OF PCP2:TSC1+/- AND PCP2:TSC1-/- PURKINJE NEURONS AFFECT THE IN VIVO ACTIVITY OF DEEP CEREBELLAR NUCLEI NEURONS, WHICH, IN THE CONTEXT OF CEREBELLAR CIRCUITS, ARE THE DOWNSTREAM TARGETS OF PURKINJE NEURONS. THESE EXPERIMENTAL AIMS WILL INVOLVE TRAINING AND COLLABORATIVE RESEARCH EFFORTS BY GRADUATE AND UNDERGRADUATE STUDENTS AT MIAMI UNIVERSITY.

SUMSRI

YOUTH AID OHIO: MENTAL HEALTH TRAININGS, RESOURCES, REFERRALS

RUI: METHANOGENESIS FROM QUATERNARY AMINES

A STUDY ON THE VERTICAL CIRCULATION AND STRUCTURE OF METALLIC IONS IN THE MID-LATITUDE IONOSPHERE

REU SITE: RESEARCH EXPERIENCE FOR UNDERGRADUATES IN CHEMISTRY AND BIOCHEMISTRY AT MIAMI UNIVERSITY

GSE/RES: THE MISSING PIECE OF THE STEM PUZZLE: THE ROLE OF COMMUNION IN WOMEN'S STEM CAREER DECISIONS

GP-EXTRA: ADVANCING UNDERGRADUATE GEOSCIENCE THROUGH INTEGRATED TRAINING EXPERIENCES (AUGITE)

FUNCTIONAL CONSEQUENCES OF MODULATION OF CPG FEEDBACK TO DESCENDING PROJECTION NEURONS

INSPIRATORY MUSCLE STRENGTH TRAINING IN PATIENTS WITH UPPER AIRWAY OBSTRUCTION

COLLABORATIVE RESEARCH: BIOCATALYTIC ALCOHOLYSIS OF PET IN NONAQUEOUS SOLVENTS FOR POLYMER RECYCLING -WITH THE ACCUMULATION OF PLASTICS IN THE ENVIRONMENT BEING ONE OF THE MOST PRESSING SOCIETAL CHALLENGES TODAY, THE DEVELOPMENT OF METHODS TO IMPROVE PLASTICS RECYCLING IS CRUCIAL. A MAJOR CHALLENGE TO PLASTICS RECYCLING IS DEVELOPING PROCESSES THAT ARE COST EFFECTIVE AND YIELD POLYMERS WITH PROPERTIES THAT ARE IDENTICAL TO OR BETTER THAN THOSE OF THE ORIGINAL PLASTIC. WHILE THE USE OF BIOLOGICAL CATALYSTS FOR POLYMER RECYCLING AND UPCYCLING HAS GENERATED SIGNIFICANT INTEREST, RESEARCH HAS BEEN RESTRICTED TO REACTIONS THAT TAKE PLACE IN WATER. DUE TO THE LIMITATIONS OF WATER AS A MEDIUM FOR SUCH REACTIONS, NEW APPROACHES THAT IMPROVE THE EFFICIENCY AND CONVERSION OF PLASTIC WASTE USING BIOLOGICALLY BASED METHODS ARE NEEDED. THE OVERALL AIM OF THIS WORK IS TO EXPLORE THE USE OF NATURAL ENZYMES TO DECONSTRUCT COMMON SINGLE-USE PLASTICS SUCH AS POLYETHYLENE TEREPHTHALATE (PET ? COMMONLY USED IN CLOTHING FIBERS AND LIQUID/FOOD CONTAINERS) IN THE ABSENCE OF BULK WATER. THIS WORK WILL SPECIFICALLY LEVERAGE THE DRAMATICALLY IMPROVED PROPERTIES OF ENZYMES IN ?DRY? ENVIRONMENTS, INCLUDING THE ABILITY TO CATALYZE A RANGE OF REACTIONS THAT ARE NOT POSSIBLE IN AQUEOUS MEDIA. THIS RESEARCH WILL INVESTIGATE ENZYMES THAT POTENTIALLY CAN DEGRADE PET IN NEW WAYS THAT FACILITATE THE REPOLYMERIZATION OF THE REACTION PRODUCTS, WHICH IS CRITICAL FOR RECYCLING. THIS EFFORT WILL LEAD TO A DETAILED UNDERSTANDING OF THE REACTION PARAMETERS THAT IMPACT ENZYME EFFICIENCY IN CONVERTING PET WASTE INTO USEFUL, RECYCLED PLASTICS BUILDING BLOCKS. THIS RESEARCH WILL BROADEN PARTICIPATION IN STEM RESEARCH BY ENGAGING A DIVERSE GROUP OF UNDERGRADUATE AND HIGH SCHOOL STUDENTS IN THIS RESEARCH PROGRAM. PARTICIPANTS WILL BE RECRUITED THROUGH A VARIETY OF PROGRAMS, INCLUDING THE SUMMER MULTICULTURAL ACCESS TO RESEARCH TRAINING (SMART) AND STEM ROUTES PROGRAMS AT CU BOULDER AND MIAMI UNIVERSITY. MOREOVER, MEANINGFUL TEACHING MODULES WILL BE DEVELOPED THAT CAN BE INCORPORATED INTO K-12 CURRICULA ON THE BIODEGRADATION OF MATERIALS AND BIOCATALYSIS. THE OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP A NOVEL BIOCATALYTIC PROCESS FOR THE DECONSTRUCTION OF POLYETHYLENE TEREPHTHALATE (PET) PLASTICS BASED ON THE ALCOHOLYSIS OF ESTER BONDS IN THE POLYMER BACKBONE BY LIPASE. OF SPECIFIC INTEREST IS CORRELATING THE KINETICS OF PET ALCOHOLYSIS WITH THE THERMODYNAMICS OF THE DEPOLYMERIZATION REACTION AS WELL AS THE SOLVENT PROPERTIES, WHICH ENABLE THE RATE OF ALCOHOLYSIS TO BE FINE-TUNED. A MAJOR ADVANTAGE OF THIS APPROACH OVER THE HYDROLYSIS OF PET IS THAT THE USE OF NONAQUEOUS MEDIA MAY PROMOTE SWELLING OF THE POLYMER, THEREBY INCREASING PLASTICITY OF THE POLYMER CHAINS. THIS IN TURN WILL INCREASE THE ACCESSIBILITY OF THE ESTER LINKAGES IN THE POLYMER BACKBONE AND THUS MAY SIGNIFICANTLY ENHANCE THE RATE OF BIOCATALYTIC CONVERSION. ADDITIONALLY, THE USE OF NONAQUEOUS SOLVENTS OVER WATER INCREASES THE EASE OF SEPARATION OF THE REACTION PRODUCTS AND CAN ENHANCE THE THERMOSTABILITY OF THE ENZYMES. THESE ADVANTAGES POTENTIALLY WILL ELIMINATE THE NEED FOR THE HIGH REACTION TEMPERATURES AS WELL AS ENERGY INTENSIVE PRETREATMENT STEPS, SUCH AS MELT EXTRUSION AND MICROGRINDING, USED IN CURRENT PET RECYCLING APPROACHES. THIS WORK WILL SPECIFICALLY TEST THE HYPOTHESIS THAT ESTERASES CAN CATALYZE THE ALCOHOLYSIS OF PET IN NONAQUEOUS MEDIA, AND THAT THE RATE OF ALCOHOLYSIS CAN BE CONTROLLED BY VARYING THE THERMODYNAMIC EQUILIBRIUM WATER ACTIVITY OF THE REACTION AS WELL AS THE SOLVENT PROPERTIES AND CHOICE OF ALCOHOL AS THE NUCLEOPHILE. THESE STUDIES WILL USE LIPASE, INCLUDING CUTINASE, AS A MODEL ESTERASE SINCE IT IS ALREADY WELL ESTABLISHED THAT LIPASES CAN CATALYZE ALCOHOLYSIS REACTIONS IN ANHYDROUS MEDIA AND BIND TO PET. ADDITIONALLY, TO CORRELATE THE KINETICS OF PET ALCOHOLYSIS WITH THE THERMODYNAMICS OF THE REACTION, WATER ACTIVITY WILL BE CONTROLLED USING SALT HYDRATES. FINALLY, AS PART OF THIS EFFORT, RATIONAL STRATEGIES WILL BE DEVELOPED TO REDUCE DIFFUSIONAL LIMITATIONS OF LIPASE IN NONAQUEOUS SOLVENTS, INCLUDING ION PAIRING WITH SURFACTANTS. WHILE THIS EFFORT WILL FOCUS ON PET RECYCLING, THE PROPOSED APPROACH MAY BE APPLICABLE IN RECYCLING OF OTHER SYNTHETIC POLYESTERS. MOREOVER, THE FUNDAMENTAL UNDERSTANDING OF DEPOLYMERIZATION REACTION MECHANISMS DEVELOPED BY THIS THIS RESEARCH PROGRAM ALSO MAY LEAD TO NEW WAYS TO CHEMICALLY MODIFY POLYESTERS TO IMPROVE THEIR UTILITY AND RECYCLABILITY. 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.