Church Of Jesus Christ Inc

ALPACA: ADVANCED CRYOGENIC L-BAND PHASED ARRAY CAMERA FOR THE ARECIBO RADIO TELESCOPE

MULTIPLEXED, NON-AMPLIFIED, NUCLEIC ACID-BASED IDENTIFICATION OF MULTIDRUG RESISTANT PATHOGENS USING AN INTEGRATED OPTOFLUIDIC PLATFORM

PHYSIOLOGICAL ROLE OF PHOSDUCINS IN THE RETINA

NEW AWARD: TESTING AND MODEL -BASED OPTIMIZATION OF COAL-FIRED PRIMARY HEATER DESIGN FOR INDIRECT SUPERCRITICAL CO2 POWER CYCLES

STRUCTURE AND FUNCTION OF PATHOGENESIS-ASSOCIATED BACTERIAL STRUCTURES BY ELECTRON CRYOTOMOGRAPHY

BRIDGING DIVIDES: A NATIONAL CIVIL DISCOURSE INITIATIVE FOR HIGHER EDUCATION

EPIDEMIOLOGY OF ALZHEIMERS DISEASE RESILIENCE AND RISK PEDIGREES

BIOCHEMICAL CONSEQUENCES OF REGIOSPECIFIC METABOLIC BIAS IN THE BRAIN

ALZHEIMER'S DISEASE IN NATIVE HAWAIIANS AND PACIFIC ISLANDERS: SAMPLE ACQUISITION AND WHOLE GENOME SEQUENCING - PROJECT SUMMARY ALZHEIMER’S DISEASE (AD) IS AMONG THE MOST SIGNIFICANT PUBLIC HEALTH AND MEDICAL CHALLENGES OF OUR DAY. APPROXIMATELY 7 MILLION AMERICANS ARE LIVING WITH AD, AND WITHOUT EFFECTIVE INTERVENTIONS, THE NUMBER WILL DOUBLE IN THE NEXT 25 YEARS. HOMOGENOUS DATASETS LIMIT THE CLINICAL UTILITY OF DISCOVERIES, POSSIBLY LEADING TO RACE-BASED DISPARITIES IN THERAPEUTICS AND DIAGNOSTIC TOOLS. ALMOST ALL AD RESEARCH DATA WERE DERIVED FROM MAJORITY-WHITE POPULATIONS IN HIGH-INCOME COUNTRIES. NATIVE HAWAIIANS AND PACIFIC ISLANDERS (NHPIS) HAVE EXCEPTIONALLY HIGH RISK. YET, DESPITE BEING THE SECOND FASTEST-GROWING RACIAL MINORITY GROUP, NHPIS ARE THE LEAST REPRESENTED RACIAL MINORITY GROUP IN LARGE REPOSITORIES/DATASETS. THE ADSP WAS INITIATED, IN PART, TO SOLVE THE GENETIC ARCHITECTURE OF AD. WHILE LIMITED DATA EXIST, AVAILABLE EVIDENCE SUGGESTS THAT THE GENETIC ARCHITECTURE OF AD IN NHPIS IS UNIQUE. FOR EXAMPLE, THE APOE SNPS ARE NOT CORRELATED WITH AD IN CHAMORROS OR POLYNESIANS. WE PLAN TO DO THE FOLLOWING. AIM 1. RECRUIT AND COLLECT DATA FROM 5,000 NHPIS. WE WILL RECRUIT 1,000 NHPIS ANNUALLY THROUGH OUR NETWORK OF CONNECTIONS, INCLUDING COMMUNITY AND RELIGIOUS LEADERS, SOCIAL MEDIA, RADIO, TV, PERSONAL CONNECTIONS, AND WORD OF MOUTH. EACH PARTICIPANT WILL COMPLETE THOROUGH HEALTH, MEDICAL, SOCIAL DETERMINANTS OF HEALTH, DIET, PHYSICAL ACTIVITY, AND DEMOGRAPHICS SURVEYS; A NEUROPHYSICAL EXAM; PROVIDE A BLOOD SAMPLE; AND AD TESTING. WE WILL COLLECT WHOLE GENOME SEQUENCES, SNP ARRAY DATA, AND STANDARD LABORATORY ASSAYS FOR EACH PARTICIPANT. AIM 2. PARTICIPANT DIAGNOSIS. EACH PARTICIPANT WILL BE DIAGNOSED USING THE NACC BATTERY AND ADJUDICATED FOLLOWING THE PROTOCOLS ESTABLISHED BY ACAD WITH MINOR ADAPTATIONS TO MAKE THE ASSESSMENTS CULTURALLY APPROPRIATE FOR NHPIS. AIM 3. GENETIC ANALYSES. WE WILL DESCRIBE NHPI GENETICS (E.G., ESTIMATE SNP FREQUENCIES IN NHPIS), ANALYZE NHPI POPULATION STRUCTURE, AND CONDUCT THE FIRST AD GWAS IN NHPIS.

COMPUTATIONAL AND EXPERIMENTAL INVESTIGATION OF CRYOGENIC GRAIN BOUNDARY MOTION FOR ENHANCED MECHANICAL PROPERTIES

CYBERCORPS SCHOLARSHIP FOR SERVICE: BUILDING RESEARCH-MINDED CYBER LEADERS -THIS PROJECT WILL ESTABLISH A NEW CYBERCORPS? SCHOLARSHIP FOR SERVICE (SFS) PROGRAM AT BRIGHAM YOUNG UNIVERSITY (BYU). OVER THE NEXT FIVE YEARS, THIS PROJECT WILL SUPPORT 23 UNDERGRADUATE AND GRADUATE STUDENTS STUDYING CYBERSECURITY. THESE FUTURE CYBER LEADERS WILL ENTER THE GOVERNMENT WORKFORCE WITH A STRONG GROUNDING IN CYBERSECURITY'S TECHNICAL AND HUMAN DIMENSIONS. SFS UNDERGRADUATE AND GRADUATE STUDENTS WILL HAVE OPPORTUNITIES TO PARTICIPATE IN FACULTY-MENTORED RESEARCH, BYU?S SECURITY OPERATIONS CENTER (SOC), A NEW CYBERCLINIC, CYBERSECURITY AND NETWORKING CLUBS, COMPETITIONS, CAREER FAIRS, GOVERNMENT INTERNSHIPS, AND OUTREACH EFFORTS. IN ADDITION, THIS PROJECT WILL ENABLE STRATEGIC ENHANCEMENTS AT BYU DESIGNED TO INCREASE THE CYBERSECURITY STUDENT DIVERSITY PROFILE, BUILD A STRONG COMMUNITY AMONG SFS STUDENTS, AND PROMOTE STUDENT RESEARCH. THIS WILL, IN TURN, PROVIDE THE GOVERNMENT WITH AN INCREASINGLY DIVERSE SET OF CAPABLE, WELL-CONNECTED GRADUATES READY TO SOLVE THE CYBERSECURITY CHALLENGES OF TODAY AND THE FUTURE. THE BYU SFS PROGRAM IS DESIGNED TO MOTIVATE STUDENTS TO BECOME ETHICAL CYBER LEADERS IN GOVERNMENT, RAISE THE VISIBILITY OF CYBERSECURITY PROGRAMS AND OPPORTUNITIES AT BYU, AND FURTHER DEVELOP PARTNERSHIPS WITH GOVERNMENT AGENCIES. THE PROJECT WILL SUPPORT AN SFS STUDENT RESEARCH SYMPOSIUM, A GOVERNMENT CYBERSECURITY CAREER EVENT TIED TO BYU?S STEM FAIR, AND NEW DIVERSITY OUTREACH EFFORTS THAT WILL BETTER INTEGRATE EFFORTS ACROSS CAMPUS (E.G., BYU ENGINEERING BE TOGETHER, WOMEN IN CYBERSECURITY CLUB, CS BELONGING, WOMEN IN COMPUTER SCIENCE, BYU MULTICULTURAL STUDENT SERVICES) AND THE COMMUNITY TO RECRUIT MORE WOMEN, MINORITIES, AND FIRST-GENERATION STUDENTS INTO THE FIELD. A NEW CYBERSECURITY SFS SEMINAR WILL HELP BUILD A COMMUNITY AMONG SFS STUDENTS AND FACULTY AND BRING IN EXPERTS FROM OTHER UNIVERSITIES AND GOVERNMENT AGENCIES. STUDENTS PARTICIPATING IN RESEARCH WILL WORK WITH FACULTY STUDYING HIGH-PRIORITY AREAS, INCLUDING AI AND CYBERSECURITY, HUMAN ASPECTS OF CYBERSECURITY, EMBEDDED SYSTEMS SECURITY, NETWORK SECURITY, AND CYBERSECURITY EDUCATION. GRADUATE SFS STUDENTS WILL COMPLETE A RIGOROUS THESIS CENTERED AROUND A CYBERSECURITY TOPIC, HELPING PREPARE THEM FOR CUTTING-EDGE RESEARCH WITHIN GOVERNMENT INSTITUTIONS. THIS PROJECT IS SUPPORTED BY THE CYBERCORPS? SCHOLARSHIP FOR SERVICE (SFS) PROGRAM, WHICH FUNDS PROPOSALS ESTABLISHING OR CONTINUING SCHOLARSHIP PROGRAMS IN CYBERSECURITY AND ALIGNS WITH THE U.S. NATIONAL CYBER STRATEGY TO DEVELOP A SUPERIOR CYBERSECURITY WORKFORCE. FOLLOWING GRADUATION, SCHOLARSHIP RECIPIENTS ARE REQUIRED TO WORK IN CYBERSECURITY FOR A FEDERAL, STATE, LOCAL, OR TRIBAL GOVERNMENT ORGANIZATION FOR THE SAME DURATION AS THEIR SCHOLARSHIP SUPPORT. 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.

I/UCRC: CENTER FOR UNMANNED AIRCRAFT SYSTEMS, PHASE II SITE

NICOTINE AND ALCOHOL CO-DEPENDENCE

IRON BASED COUPLING MEDIA (IBCM) FOR MRI-GUIDED TRANSCRANIAL ULTRASOUND SURGERIES - PROJECT SUMMARY/ABSTRACT FATAL OR IMPAIRING NEUROLOGICAL DISEASES, INCLUDING MOVEMENT DISORDERS, BRAIN CANCERS, PSYCHOLOGICAL DISORDERS, EPILEPSIES, MALFORMATIONS, AND MEMORY DISORDERS, IMPOSE HEAVY BURDENS ON BOTH INDIVIDUALS AND SOCIETY AT LARGE. TRANSCRANIAL MAGNETIC RESONANCE GUIDED FOCUSED ULTRASOUND SURGERY (TMRGFUS) IS AN EXTREMELY PROMISING, MINIMALLY INVASIVE TREATMENT MODALITY FOR NEUROLOGICAL DISEASES WHEREBY SOUND WAVES ARE FOCUSED TO A SPECIFIC REGION OF THE BRAIN. BECAUSE IT IS NONINVASIVE, THE EFFICACY OF TMRGFUS PROCEDURE HEAVILY RELIES ON THE ACCURACY AND INFORMATION CONTENT OF THE GUIDANCE TECHNOLOGY. THIS STUDY PROPOSES TO IMPROVE THE TREATMENT EFFICACY OF NEARLY ALL TMRGFUS SURGERIES BY ELIMINATING A UBIQUITOUS IMPEDIMENT TO ACCURATE AND INFORMATION-RICH GUIDANCE MRI: THE ACOUSTIC COUPLING MEDIUM. INTERACTIONS BETWEEN THE COUPLING MEDIA AND GUIDANCE IMAGING IMPEDE TMRGFUS EFFICACY AND TRANSLATION. FOR EXAMPLE, WHILE FDA-APPROVED TMRGFUS TREATMENTS FOR ESSENTIAL TREMOR AND PARKINSON’S DISEASE CAN RELY ON REAL-TIME PATIENT FEEDBACK TO COMPENSATE FOR ERRORS IN GUIDANCE MR IMAGING, OTHER TMRGFUS INDICATIONS CANNOT ACCESS PATIENT FEEDBACK BECAUSE EITHER THE PATIENT IS UNCONSCIOUS, OR THE CONSEQUENCES OF TREATMENT ERRORS APPEAR ONLY DAYS LATER. IN THESE CASES, GUIDANCE IMAGING ERRORS IMPOSED BY THE COUPLING BATH CANNOT BE COMPENSATED AND DEGRADE TREATMENT EFFICACY TO MEET THIS NEED, OUR STUDY PROPOSES A DILUTE, IRON-BASED COUPLING MEDIA (IBCM) THAT WILL ELIMINATE COUPLING- MEDIA-INDUCED ERRORS IN MRI GUIDANCE IMAGING WHILE MAINTAINING THE COUPLING AND COOLING FUNCTIONALITY CRITICAL TO ACOUSTIC TRANSMISSION. THE SPECIFIC AIMS OF THE STUDY ARE AS FOLLOWS. AIM 1: DEVELOP NOVEL SURFACE–MODIFIED IRON OXIDE NANOPARTICLES FOR AN IBCM. DILUTE, AQUEOUS, SURFACE- MODIFIED IRON OXIDE NANOPARTICLES CAN ACCELERATE MRI SIGNAL DECAY SUCH THAT, DURING IMAGE ACQUISITION, A COUPLING MEDIUM WILL CONTRIBUTE NEGLIGIBLE EFFECTS TO GUIDANCE IMAGING. HOWEVER, AQUEOUS NANOPARTICLES ALSO AGGLOMERATE AND SEED TREATMENT-IMPEDING CAVITATION NUCLEATION IN THE PREFOCAL ACOUSTIC FIELD. THIS AIM WILL DEVELOP NOVEL SURFACE-MODIFIED PARTICLES THAT, UPON SUSPENSION, ACCELERATE MRI SIGNAL DECAY WITHOUT PROMOTING PREFOCAL NUCLEATION. AIM 2: INVESTIGATE THE EFFECTS OF IBCM SUSPENSION FLUID PROPERTIES ON CAVITATION NUCLEATION. FLUID PROPERTIES PLAY A CRITICAL ROLE IN PARTICLE SUSPENSION, ACOUSTIC COUPLING, SUBJECT COOLING, AND CAVITATION NUCLEATION. THIS AIM WILL INVESTIGATE CAVITATION NUCLEATION WITHIN THE IBCM AND HOW SUSPENSION FLUID PROPERTIES, SUCH AS PH, TEMPERATURE, GAS CONTENT, AND FLOW STATE, CAN MODIFY OR SUPPRESS THE NUCLEATION PROCESS WHILE MAINTAINING SUSPENSION, COUPLING, AND COOLING CAPABILITIES. AIM 3: ENHANCE MRI GUIDANCE FOR TMRGFUS THROUGH THE USE OF AN IBCM. THIS AIM WILL QUANTIFY THE VALUE OF THE IBCM DESIGNED IN AIMS 1 AND 2 FOR TMRGFUS BY MEASURING IMAGE QUALITY METRICS DERIVED FROM GUIDANCE MRI SCANS OF HUMAN SUBJECTS. THIS AIM WILL ALSO DEVELOP NOVEL MRI GUIDANCE TECHNIQUES THAT WERE PREVIOUSLY RENDERED IMPOSSIBLE DUE TO SEVERE IMAGE CORRUPTIONS IMPOSED BY THE ACOUSTIC COUPLING MEDIUM. THE RESULTING IBCM WILL IMPROVE IMAGE QUALITY FOR NEARLY ALL GUIDANCE TECHNIQUES EMPLOYED DURING, OR UNDERGOING DEVELOPMENT FOR, TMRGFUS, BY RENDERING THE ACOUSTIC COUPLING MEDIUM INVISIBLE TO THE MRI SCANNER WITHOUT SACRIFICING NECESSARY ACOUSTIC COUPLING AND COOLING FUNCTIONALITY.

ENHANCED SENSITIVITY AND QUANTITATIVE PRECISION FOR SINGLE CELL PROTEOMICS - SINGLE CELL PROTEOMICS (SCP) IS RAPIDLY EMERGING AND CAN QUANTIFY > 1000 PROTEINS PER CELL. SIGNIFICANT ADVANCES IN INSTRUMENTATION AND SAMPLE PREPARATION ARE MAKING SCP MORE BROADLY ACCESSIBLE. YET TECHNICAL ADVANCES IN DATA ACQUISITION HAVE NOT BEEN PAIRED WITH ADVANCES TO COMPUTATIONAL TOOLS. ALGORITHMS FOR PROTEOMICS WERE DESIGNED AND OPTIMIZED ON DATA FROM BULK PROTEOMICS, AND ARE ILL-SUITED FOR SCP DATA. OUR PRELIMINARY RESEARCH SHOWS THAT DATA FROM SCP LACK MANY FEATURES THAT ARE CRITICAL FOR CURRENT PROTEOMICS ALGORITHMS. WE WILL DRAMATICALLY IMPROVE ACCURACY AND COVERAGE OF THE SINGLE CELL PROTEOME THROUGH CREATION OF THE FIRST-EVER DEDICATED SCP SEARCH SOFTWARE. THIS WILL BE COUPLED WITH AN INITIATIVE TO IMPROVE SCP PEPTIDE AND PROTEIN QUANTIFICATION. THESE ALGORITHMIC IMPROVEMENTS WILL BE INFORMED FROM A LARGE CORPUS OF SCP DATA, GATHERED AND CENTRALIZED INTO THE FIRST SCP DATA ARCHIVE.

ASSESSING THE INFLUENCE OF SPACE LAUNCH AND LANDING NOISE ON SPECIES OF CONCERN AT VANDENBERG SPACE FORCE BASE.

ADVANCED SAMPLE PREPARATION, SEPARATION AND MULTIPLEXED ANALYSIS FOR IN-DEPTH PROTEOME PROFILING OF >1000 SINGLE CELLS PER DAY - PROJECT SUMMARY/ABSTRACT CANCER TISSUES EXHIBIT A HIGH DEGREE OF PHENOTYPIC HETEROGENEITY AND PLASTICITY AND CONTAIN NUMEROUS SUBPOPULATIONS OF CELLS IN VARIOUS STATES. QUANTIFYING THIS HETEROGENEITY AT THE SINGLE-CELL LEVEL AND WITH MOLECULAR DEPTH ACROSS LARGE NUMBERS OF CELLS PROVIDES INFORMATION THAT CANNOT BE OBTAINED AT THE BULK SCALE AND WILL ULTIMATELY LEAD TO IMPROVED DIAGNOSTICS AND MORE EFFECTIVE TREATMENTS. WHILE SINGLE-CELL NUCLEIC ACID SEQUENCING APPROACHES ARE HAVING A SIGNIFICANT IMPACT ON CANCER RESEARCH, PROTEINS MEDIATE THE BULK OF CELLULAR FUNCTION AND ARE THE TARGETS OF MOST THERAPEUTICS. THERE IS THUS AN URGENT NEED TO DEVELOP NEW TECHNOLOGIES FOR LARGE- SCALE DIRECT PROTEOME PROFILING AT THE SINGLE-CELL LEVEL. TO FILL THIS GAP, MASS SPECTROMETRY (MS)-BASED PROFILING OF PROTEIN EXPRESSION IN SINGLE CELLS HAS RECENTLY BEEN DEMONSTRATED THROUGH THE IMPLEMENTATION OF MORE EFFICIENT SAMPLE PROCESSING WORKFLOWS, NOVEL EXPERIMENTAL DESIGNS AND IMPROVED INSTRUMENT SENSITIVITY. LABEL-FREE MS- BASED PROTEOMICS CAN NOW QUANTIFY >2,000 PROTEIN GROUPS PER CELL ACROSS >4 ORDERS OF MAGNITUDE OF DYNAMIC RANGE, BUT EFFORTS TO PROFILE MORE THAN A FEW DOZEN CELLS PER DAY HAVE RESULTED IN SIGNIFICANTLY REDUCED PROTEOME COVERAGE. THIS LOW THROUGHPUT IS INSUFFICIENT FOR THE LARGE-SCALE STATISTICALLY POWERED STUDIES REQUIRED TO CHARACTERIZE HETEROGENEITY IN CANCER CELL POPULATIONS. TO INCREASE MEASUREMENT THROUGHPUT, MULTIPLEXED WORKFLOWS BASED ON ISOBARIC TANDEM MASS TAGS (TMTS) ENABLE UP TO 18 SINGLE CELLS TO BE MEASURED IN AN LC- MS ANALYSIS, BUT THESE HAVE STILL BEEN LIMITED TO ~100 CELLS/DAY AND, AS GENERALLY IMPLEMENTED, SUFFER FROM A LARGE PROPORTION OF MISSING VALUES AND OTHER ISSUES AFFECTING QUANTITATIVE PERFORMANCE. OUR OVERALL OBJECTIVE IS TO DEVELOP A PLATFORM THAT COMBINES SIMPLIFIED PIPETTE-FREE HIGH-THROUGHPUT SAMPLE PREPARATION WITH RAPID, MULTICOLUMN LIQUID CHROMATOGRAPHY SEPARATIONS AND ‘GREEDY’ DATA-DEPENDENT ACQUISITION TO PROFILE >2000 PROTEINS PER CELL WITH A MEASUREMENT THROUGHPUT OF >1000 SINGLE CELLS PER DAY. WE HYPOTHESIZE THAT THE ADVANCED SAMPLE PREPARATION AND SEPARATION, COMBINED WITH A FAR MORE EFFICIENT MS ACQUISITION WORKFLOW, WILL ACHIEVE IN-DEPTH SCP WITH A 10× THROUGHPUT GAIN, THUS PROVIDING A CAPABILITY FOR DIRECT, IN-DEPTH AND LARGE-SCALE PROTEIN QUANTIFICATION THAT IS ANALOGOUS TO SINGLE-CELL RNA-SEQ. STUDIES IN AIM 1 WILL FOCUS ON DEVELOPING MASSIVELY PARALLEL CENTRIFUGAL NANOLITER DISPENSING TO PREPARE >10,000 SINGLE-CELLS PER DAY AT A TOTAL REAGENT AND CONSUMABLES COST OF <$0.40/CELL. IN AIM 2, WE WILL DEVELOP RAPID, ROBUST AND HIGH-PEAK-CAPACITY 20-MIN NANOLC SEPARATIONS WITH 100% DUTY CYCLE. IN AIM 3, WE WILL DEVELOP A NOVEL ‘GREEDY’ DATA ACQUISITION STRATEGY IN WHICH ONLY PROTEOTYPIC PEPTIDES ARE SELECTED FOR FRAGMENTATION, AND WITH CUSTOM AUTOMATIC GAIN CONTROL SETTINGS AND FRAGMENTATION ENERGY FOR EACH PEPTIDE, PROVIDING AN UNPRECEDENTED COMBINATION OF SENSITIVITY AND THROUGHPUT. WITH THIS NEXT-GENERATION PLATFORM, WE WILL PROFILE >10,000 CELLS TO STUDY ACQUIRED RESISTANCE TO AUTOPHAGY INHIBITORS IN THE CONTEXT OF AUTOPHAGY-DEPENDENT TRIPLE NEGATIVE BREAST CANCER, THUS ESTABLISHING AN INNOVATIVE PLATFORM FOR ADVANCING BIOMEDICAL RESEARCH AND INDIVIDUALIZING THERAPY.

FULLY AUTOMATED AND ULTRA-HIGH-THROUGHPUT PLATFORM FOR IN-DEPTH SINGLE-CELL PROTEOMICS

DEVELOPING THE PEDAGOGICAL SKILLS AND SCIENCE EXPERTISE OF TEACHERS IN UNDERSERVED RURAL SETTINGS

AREA A: IN-DEPTH PROTEOME MAPPING OF THE TUMOR MICROENVIRONMENT WITH SINGLE-CELL RESOLUTION

BULKY DEHYDROAMINO ACIDS AS CONSTRAINING AND STABILIZING COMPONENTS OF PEPTIDES

COLLABORATIVE RESEARCH: DESIGNING A TEACHER LEARNING SEQUENCE FOR BUILDING ON MATHEMATICAL OPPORTUNITIES IN STUDENT THINKING -MATHEMATICAL OPPORTUNITIES IN STUDENT THINKING (MOSTS) ARE HIGH-LEVERAGE INSTANCES OF STUDENT MATHEMATICAL THINKING THAT EMERGE IN WHOLE-CLASS DISCUSSIONS. THE CHALLENGE FOR TEACHERS IS TO BUILD ON THESE OPPORTUNITIES TO HELP THE WHOLE CLASS UNDERSTAND THE MATHEMATICS UNDERLYING THESE STUDENT CONTRIBUTIONS. TO HELP TEACHERS LEARN HOW TO BUILD ON MOSTS, THERE IS A NEED FOR PROFESSIONAL DEVELOPMENT RESOURCES AND TOOLS THAT FACILITATORS CAN USE. THERE IS ALSO A NEED FOR RESEARCH ABOUT HOW TEACHERS USE WHAT THEY LEARN IN PROFESSIONAL DEVELOPMENT IN THEIR TEACHING. THIS PROJECT IS DEVELOPING A TEACHER LEARNING SEQUENCE THAT WILL SUPPORT TEACHERS IN LEARNING TO PRODUCTIVELY USE STUDENT THINKING THAT SURFACES IN-THE-MOMENT DURING THEIR INSTRUCTION?THAT IS, IN LEARNING TO BUILD ON MOSTS. THIS PROJECT BUILDS ON PRIOR WORK THAT DEVELOPED A FRAMEWORK FOR RECOGNIZING MOSTS AND CONCEPTUALIZED THE BUILDING PRACTICE TEACHERS USE TO EFFECTIVELY CAPITALIZE ON MOSTS. THE OVERARCHING RESEARCH QUESTION FOR THE PROJECT IS: TO WHAT EXTENT DOES THE PROFESSIONAL LEARNING SEQUENCE HELP TEACHERS UNDERSTAND AND ENACT THE TEACHING PRACTICE OF BUILDING? AS PART OF THIS INVESTIGATION, THE PROJECT ALSO CONSIDERS FACTORS THAT MIGHT MITIGATE TEACHERS? LEARNING, SUCH AS TEACHER ATTRIBUTES (KNOWLEDGE, PRACTICES, OR EXPERIENCES) AND CONTEXTUAL FACTORS. THE STUDY USES A DESIGN RESEARCH FRAMEWORK TO DOCUMENT HOW TEACHERS TAKE UP ASPECTS OF BUILDING ON MOSTS FROM THE PROFESSIONAL DEVELOPMENT, THE PROCESS OF TEACHERS? LEARNING, AND CHANGES IN THEIR CLASSROOM PRACTICE. THE STUDY RELIES ON DATA FROM THE PROFESSIONAL DEVELOPMENT ACTIVITIES, TEACHER SURVEYS AND INTERVIEWS, AND CLASSROOM DATA. THE PROJECT SITES INCLUDE SECONDARY SCHOOLS IN URBAN AND RURAL SETTINGS. THE DISCOVERY RESEARCH PREK-12 PROGRAM (DRK-12) IS AN APPLIED RESEARCH PROGRAM THAT SEEKS TO SIGNIFICANTLY ENHANCE THE LEARNING AND TEACHING OF SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) BY PREK-12 STUDENTS AND TEACHERS. PROJECTS IN THE DRK-12 PROGRAM BUILD ON FUNDAMENTAL RESEARCH IN STEM EDUCATION AND PRIOR RESEARCH AND DEVELOPMENT EFFORTS THAT PROVIDE THEORETICAL AND EMPIRICAL JUSTIFICATION FOR FUNDED PROJECTS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

MOLECULAR MECHANISMS OF YEAST PAS KINASE REGULATION AND FUNCTION.

NEUROIMMUNE MECHANISMS OF ALCOHOL REWARD - PROJECT SUMMARY/ABSTRACT THE PREVAILING DOGMA IN THE ALCOHOL FIELD IS THAT THE REWARDING PROPERTIES OF ETHANOL (ETOH) RESULT FROM ENHANCEMENT OF VENTRAL TEGMENTAL AREA (VTA) DOPAMINE (DA) NEURAL ACTIVITY AND ACCOMPANYING DA RELEASE IN THE MESOLIMBIC REWARD SYSTEM. IN PRELIMINARY STUDIES, WE WILL DEMONSTRATE THAT SOME OF ETOH’S EFFECTS ON MIDBRAIN NEURONS AND NAC DA RELEASE ARE MEDIATED BY PERIPHERAL SUBSTRATES INCLUDING DA D2-SUBTYPE 2 RECEPTOR (D2R) EXPRESSING MONOCYTE-DERIVED MACROPHAGES (MDMS). THESE FINDINGS SUGGEST A NEUROIMMUNE INTERACTION FOR ACUTE ETOH USE AND CHALLENGE THE DOGMA THAT ETOH HAS EXCLUSIVELY CENTRAL EFFECTS ON DA NEURONAL ACTIVITY, RELEASE, AND REWARD. OUR PROPOSED STUDIES CONSTITUTE A FOCUSED INVESTIGATION INTO THE ROLE OF NEUROIMMUNE INTERACTIONS IN ETOH EFFECTS ON VTA NEURONS, DA TRANSMISSION, AND ETOH REWARD AND CONSUMPTION. THE CORE THESIS IS THAT ACUTE ETOH ENHANCEMENT OF MESOLIMBIC DA TRANSMISSION AND ETOH REWARD IS MEDIATED BY ETOH ENHANCEMENT OF BLOOD DA, SUBSEQUENT ACTIVATION OF D2R-EXPRESSING MDMS, AND SUBSEQUENT CYTOKINE MODULATION OF VTA NEURONS, THAT ARE RESPONSIBLE FOR CHRONIC ADAPTATIONS IN VTA GABA NEURONS AND DA RELEASE. PRIOR AND PRELIMINARY EVIDENCE SUPPORTING OUR HYPOTHESIS INCLUDE: 1) PERIPHERAL DA INCREASES THE ACTIVITY OF DA NEURONS AND NAC DA RELEASE, REDUCES LOCOMOTOR ACTIVITY, AND PROMOTES REWARD VIA PERIPHERAL D2RS; 2) ETOH ENHANCES BLOOD DA, INHIBITS VTA GABA NEURONS, ENHANCES BRAIN DA, AND REDUCES INTOXICATION VIA PERIPHERAL D2RS; 3) ETOH INDUCES MICROGLIA ACTIVATION AND ENHANCES D2 RECEPTOR EXPRESSION ON MONOCYTES, NEURONS, AND MICROGLIA; 4) DEPLETION OF MDMS REDUCES ETOH EFFECTS ON VTA GABA NEURONS AND DA RELEASE; 5) SELECT CYTOKINES ENHANCE VTA NEURON EXCITABILITY AND DA RELEASE; 6) LAST, WE SHOW PRELIMINARY EVIDENCE OF DA AND ATP CO-RELEASE FROM DA TERMINALS, AND MOTILITY EFFECTS OF ETOH ON MICROGLIA, WHICH INDICATE FURTHER STUDY FOR POTENTIAL NAC ETOH IMMUNE INTERACTIONS IN VIVO. THESE DATA WILL PROVIDE NEW, FUNDAMENTAL KNOWLEDGE ON THE NEUROBIOLOGY OF ETOH REWARD AND DEPENDENCE AND THE ROLE OF PERIPHERAL SUBSTRATES THAT MAY HELP IMPROVE DRUG DEVELOPMENT EFFORTS. TO TEST THE HYPOTHESES, WE PROPOSE TWO SPECIFIC AIMS: 1) DEFINE THE ROLE OF PERIPHERAL NEUROIMMUNE INTERACTIONS IN ETOH EFFECTS ON VTA GABA NEURONS AND NAC DA RELEASE, AND RELATED BEHAVIORS; 2) DESCRIBE EFFECTS OF ETOH ON NAC DA TERMINALS AND MICROGLIA, CO-RELEASE OF DA AND ATP. WE WILL USE WILD-TYPE AND TRANSGENIC MOUSE MODELS (GAD67-GFP KNOCK-IN; VGAT-CHR2, VGAT-CRE/GAD67-GFP; AND MAFIA MICE) AND MDM DEPLETION TO STUDY NEUROCHEMICAL AND ELECTROCHEMICAL RECORDINGS OF DA RELEASE. CYTOMETRY TECHNIQUES WILL BE USED TO DETERMINE CYTOKINE FACTORS INVOLVED IN MESOLIMBIC ALTERATIONS. MULTIPHOTON MICROSCOPY APPROACHES TO STUDY MICROGLIA CHEMOTAXIS IN THE CONTEXT OF DA AND ATP AS MEASURED BY FAST SCAN CYCLIC VOLTAMMETRY. MULTIPHOTON MICROSCOPY WILL BE USED IN VIVO THROUGH ENDOSCOPIC RELAY GRADIENT INDEX LENSES TO STUDY GFP LABELED SATELLITE MICROGLIA SURVEILLANCE WHILE MEASURED DOPAMINE RELEASE USING A RED SHIFTED OPTICAL SENSOR FOR DETECTING DA RELEASE, WHICH WILL BE PERFORMED ON MICE UNDERGOING CHRONIC INTERMITTENT ETOH (CIE) INDUCTION, THUS DESCRIBING NEUROIMMUNE ACTIVITY FROM FIRST EXPOSURE TO ETOH, THROUGH TO DEPENDENCE. SCIENTIFIC RIGOR IS HIGH CONSIDERING THE USE OF CONVENTIONAL BEHAVIORAL, PHARMACOLOGICAL, ELECTROCHEMICAL, MICROSCOPY AND MOLECULAR TOOLS.

HIGH DENSITY 3D PRINTED MICROFLUIDICS WITH OPEN SOURCE RESINS FOR BIOMEDICAL APPLICATIONS

WEARABLE NANOCOMPOSITE SENSOR SYSTEM FOR DIAGNOSING MECHANICAL SOURCES OF LOW BACK PAIN AND GUIDING REHABILITATION - PROJECT SUMMARY BACK PAIN HAS GAINED THE DISTINCTION OF BEING THE MOST DISABLING CONDITION IN THE WORLD [1-3], AFFECTING 80-90% OF THE US POPULATION AT SOME POINT IN THEIR LIFETIME, WITH 29% OF THE US POPULATION HAVING EXPERIENCED LOWER BACK PAIN WITHIN THE LAST 3 MONTHS. BACK AND NECK PAIN ARE THE LEADING CAUSE OF MISSED WORK DAYS AND RANK SECOND ONLY TO THE COMMON COLD AS A REASON FOR A VISIT TO THE DOCTOR, ACCOUNTING FOR APPROXIMATELY 30% OF GENERAL PRACTITIONER VISITS. OF PARTICULAR CONCERN IS CHRONIC LOW BACK PAIN (CLBP), WHICH IS RECURRENT AND OFTEN NON-RESPONSIVE TO CONSERVATIVE TREATMENTS. IT HAS LONG BEEN RECOGNIZED THAT SPINAL PATHOLOGY CHANGES THE WAY THAT WE MOVE. BIOMECHANISTS, PHYSICAL THERAPISTS, AND SURGEONS EACH UTILIZE A VARIETY OF TOOLS AND TECHNIQUES TO ASSESS AND INTERPRET QUALITATIVE MOVEMENT CHANGES AS A WINDOW TO UNDERSTANDING POTENTIAL MECHANICAL AND NEUROLOGICAL SOURCES OF LOW BACK PAIN AND AS A CRITICAL ELEMENT IN THEIR TREATMENT PARADIGM. HOWEVER, OBJECTIVELY CHARACTERIZING AND COMMUNICATING THIS INFORMATION IS CURRENTLY IMPOSSIBLE, SINCE CLINICALLY FEASIBLE (E.G., COST-EFFECTIVE, OBJECTIVE, AND ACCURATE) TOOLS AND QUANTITATIVE BENCHMARKS DO NOT EXIST. THIS PROPOSAL ADDRESSES THE CHALLENGE TO IMPROVE CLBP OUTCOMES THROUGH THE USE OF UNIQUE, INEXPENSIVE, SCREEN-PRINTABLE, ELASTOMER-BASED NANO-COMPOSITE PIEZORESPONSIVE SENSORS WHICH WILL BE INTEGRATED INTO A SPINAL NANOSENSOR ENVIRONMENT (SPINE SENSE SYSTEM) TO MEASURE LUMBAR KINEMATICS AND PROVIDE AN OBJECTIVE, QUANTITATIVE PLATFORM FOR DIAGNOSIS, MONITORING, AND FOLLOW-UP ASSESSMENT OF CLBP.

MASS SPECTROMETRY-BASED BIOCHEMICAL ANALYSIS OF SINGLE CELLS BEYOND THE GLOBAL PROTEOME - PROJECT SUMMARY/ABSTRACT BIOLOGICAL TISSUES EXHIBIT A HIGH DEGREE OF PHENOTYPIC HETEROGENEITY AND PLASTICITY, COMPRISING MANY DIFFERENT SUBPOPULATIONS OF CELLS IN VARIOUS STATES. QUANTIFYING THIS HETEROGENEITY AT THE SINGLE-CELL LEVEL AND WITH MOLECULAR DEPTH ACROSS LARGE NUMBERS OF CELLS AND MULTIPLE CLASSES OF MOLECULES PROVIDES INFORMATION THAT CANNOT BE OBTAINED AT THE BULK SCALE AND WILL ULTIMATELY LEAD TO IMPROVED DIAGNOSTICS AND MORE EFFECTIVE TREATMENTS. WHILE SINGLE-CELL NUCLEIC ACID SEQUENCING APPROACHES ARE HAVING A SIGNIFICANT IMPACT ON BIOMEDICAL RESEARCH, PROTEINS, LIPIDS AND METABOLITES MEDIATE THE BULK OF CELLULAR FUNCTION AND MEASUREMENT OF THEIR EXPRESSION PROVIDES MORE DIRECT INSIGHT INTO CELLULAR PHENOTYPE. THERE IS THUS AN URGENT NEED TO DEVELOP NEW TECHNOLOGIES FOR LARGE-SCALE DIRECT PROTEOME, LIPIDOME AND METABOLOME PROFILING AT THE SINGLE-CELL LEVEL. TO FILL THIS GAP, MASS SPECTROMETRY (MS)-BASED PROFILING OF PROTEIN EXPRESSION IN SINGLE CELLS HAS RECENTLY BEEN DEMONSTRATED THROUGH THE IMPLEMENTATION OF MORE EFFICIENT SAMPLE PROCESSING WORKFLOWS, NOVEL EXPERIMENTAL DESIGNS AND IMPROVED INSTRUMENT SENSITIVITY. LABEL-FREE MS-BASED PROTEOMICS CAN NOW QUANTIFY >3,000 PROTEIN GROUPS PER CELL ACROSS >4 ORDERS OF MAGNITUDE OF DYNAMIC RANGE. HERE WE PROPOSE TO APPLY MASS SPECTROMETRY TO STUDY BIOMOLECULAR EXPRESSION AT THE SINGLE-CELL LEVEL BEYOND THE GLOBAL PROTEOME. WE WILL DEVELOP GLOBAL AND TARGETED APPROACHES TO PROFILE POSTTRANSLATIONAL MODIFICATIONS IN SINGLE CELLS, BEGINNING WITH PHOSPHORYLATION. WE WILL ALSO EXTEND NANOFLOW LIQUID CHROMATOGRAPHY-MS CAPABILITIES FOR IN-DEPTH SINGLE-CELL LIPID PROFILING. ULTIMATELY, WE WILL DEVELOP NOVEL MEANS OF GENERATING COMPLEX LC GRADIENTS THAT UTILIZE MORE THAN TWO MOBILE PHASES TO EFFICIENTLY PROFILE MULTIPLE CLASSES OF BIOMOLECULES (E.G., PROTEOME AND LIPIDOME) FROM THE SAME SINGLE CELL. THESE RESEARCH DIRECTIONS WILL, IN COMBINATION WITH MATURE NUCLEIC ACID SEQUENCING STRATEGIES, PROVIDE AN UNPRECEDENTED VIEW OF CELLULAR REGULATION FROM GENOTYPE TO PHENOTYPE AT THE SINGLE-CELL LEVEL.

PHASE I IUCRC BRIGHAM YOUNG UNIVERSITY: CENTER FOR SPACE, HIGH-PERFORMANCE, AND RESILIENT COMPUTING (SHREC)

ADVANCING THE NASA GEOGLOWS TOOLBOX FOR REGIONAL WATER RESOURCES MANAGEMENT AND DECISION SUPPORT

INTBIO: COLLABORATIVE RESEARCH: SILK PROTEIN INNOVATION AND NOVELTY (SPIN) : INTEGRATING ACROSS DISCIPLINES TO DECIPHER SILK FIBER EVOLUTION -SILK IS ONE OF NATURE?S STRONGEST AND LIGHTEST BIOMATERIALS. IT IS USED BY HUNDREDS OF THOUSANDS OF SPECIES FOR AN ARRAY OF APPLICATIONS. YET, OUTSIDE OF A FEW SPECIES, LITTLE IS KNOWN ABOUT THE GENOMIC BASIS AND MATERIAL PROPERTIES OF NATURAL SILKS. THIS PROJECT TAKES AN INTEGRATIVE APPROACH TO EXAMINE THE MOLECULAR, DEVELOPMENTAL, AND FUNCTIONAL BASIS OF SILK ACROSS A DIVERSITY OF USES. AN INTEGRATIVE TEAM OF NATURAL HISTORIANS, MOLECULAR BIOLOGISTS, DEVELOPMENTAL BIOLOGISTS, AND BIOENGINEERS ARE COMBINING THEIR EXPERTISE TO GAIN INSIGHT INTO HOW NATURE SHAPES SILK FIBER FUNCTION. THIS RESEARCH IS FOUNDATIONAL TO ENGINEERING NEW MATERIALS THAT CAN APPLIED TO MANY PRODUCTS, FROM SURGICAL ADHESIVES TO SUSTAINABLE CLOTHING. AS PART OF THIS PROJECT, MULTIPLE POSTDOCTORAL RESEARCHERS AND GRADUATE STUDENTS GAIN INTERDISCIPLINARY TRAINING IN GENOMICS, GENE EDITING, AND ENGINEERING. FURTHERMORE, THIS PROJECT CREATES A TRAVELING MUSEUM EXHIBIT TO EDUCATE THE PUBLIC ABOUT THE NATURAL PROPERTIES OF SILK. SILK HAS BEEN SHAPED AND RE-ADAPTED FOR AN EXTRAORDINARY DIVERSITY OF USES ACROSS MULTIPLE DISTANTLY RELATED ARTHROPOD GROUPS AND HUNDREDS OF MILLIONS OF YEARS OF EVOLUTION. TO DATE, SILK RESEARCH IN INSECTS HAS FOCUSED LARGELY ON FIBERS FROM THE DOMESTICATED SILKWORM MOTH, BOMBYX MORI. THIS PROJECT USES A COMPARATIVE, MULTI-TIERED APPROACH TO STUDY SILKS OF THE MOST DOMINANT CLADE OF SILK-PRODUCING INSECTS, THE CADDISFLIES AND MOTHS. THE COMBINATION OF GENOMICS, PROTEOMICS, FUNCTIONAL GENETICS, AND BIOPHYSICAL MEASUREMENTS WILL ILLUMINATE HOW SILKS ADHERE TO UNDERWATER SUBSTRATES, HOW THEY CONSOLIDATE INTO AN INSOLUBLE FIBER, AND HELP UNDERSTAND THE MOLECULAR BASIS OF THEIR MECHANICAL PROPERTIES. EVOLUTIONARY CORRELATIONS ARE WOVEN BETWEEN GENOTYPES AND PHENOTYPES AND DIRECT TESTS OF CAUSALITY ARE CONDUCTED IN STRATEGICALLY CHOSEN FOCAL SPECIES THAT ARE AMENABLE TO GENETIC MODIFICATION. OVERALL, THIS PROJECT ADDRESSES THE OVERARCHING QUESTION, ?HOW DOES NATURE SHAPE SILK FIBER FUNCTION?? WITH A NEW FRAMEWORK FOR A FUNDAMENTAL BIOLOGICAL SUPERSTRUCTURE THAT HAS UNTAPPED POTENTIAL FOR THE PRODUCTION OF NEW POLYMER-BASED BIOMATERIALS. 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.

2018-2022 CENTER FOR INTERNATIONAL BUSINESS EDUCATION GRANT

DEVELOPMENT OF ENABLING TECHNOLOGIES FOR A PRESSURIZED DRY FEED OXY-COAL REACTOR

CENTERS FOR INTERNATIONAL BUSINESS EDUCATION

3D-PRINTED INTEGRATED MICROFLUIDIC DEVICES FOR PRETERM BIRTH BIOMARKER ANALYSIS

THE CAUSES OF GEOGRAPHIC VARIATION IN DROSOPHILA MELANOGASTER MICROBIOTA COMPOSITION

HELPING PRODUCERS IMPROVE WILDLIFE HABITAT WITH INNOVATIVE SED COATING TECHNOLOGIES

MRI: DEVELOPMENT OF A LOCAL AIR TRAFFIC INFORMATION SYSTEM (LATIS) FOR UAS COLLISION AVOIDANCE RESEARCH

EXPANDING THE CAPABILITIES AND USAGE OF THE TELSAM PROTEIN CRYSTALLIZATION CHAPERONE - THERE IS A CRITICAL NEED FOR NEW PROTEIN CRYSTALLIZATION METHODS THAT ARE MORE SUCCESSFUL AND REQUIRE LESS LABOR, TIME, AND RESOURCES. LACK OF STRAIGHTFORWARD METHODS TO SUCCESSFULLY CRYSTALLIZE ANY PROTEIN OF INTEREST SIGNIFI- CANTLY HINDERS STUDY OF MOLECULAR DISEASE MECHANISMS AND THE DEVELOPMENT OF EFFECTIVE TREATMENTS. THIS LACK OF EFFECTIVE TREATMENTS FOR MANY DISEASES FORCES THEM TO BE ADDRESSED INSTEAD WITH COSTLY SYMPTOM MANAGEMENT PROGRAMS. OVER THE PAST FOUR YEARS, WE HAVE INVESTIGATED TELSAM, A NOVEL POLYMER-FORMING PROTEIN CRYSTALLIZA- TION CHAPERONE. TELSAM CARRIER PROTEINS CAN BE GENETICALLY FUSED TO DISEASE PROTEINS, DRUG TARGETS, AND BIOEN- GINEERED PROTEINS. IN LOW PH CRYSTALLIZATION CONDITIONS, TELSAM-TARGET PROTEIN FUSIONS POLYMERIZE, AND THE RE- SULTING POLYMERS ZIPPER UP TO FORM CRYSTALS SUITABLE FOR X-RAY DIFFRACTION AND ATOMIC RESOLUTION STRUCTURE DETERMI- NATION. TELSAM FUSION READILY FORMS CRYSTALS OF 90% OF PROTEINS OF INTEREST (A STARK IMPROVEMENT OVER THE 30% CRYSTALLIZATION RATE OF TRADITIONAL METHODS) AND ROUTINELY AT PROTEIN CONCENTRATIONS OF 1 MG/ML (PROMISING TO ENABLE THE STRUCTURE DETERMINATION OF PROTEINS THAT CAN ONLY BE PRODUCED IN MINUTE QUANTITIES). TELSAM FUSION CRYSTAL- LOGRAPHY THUS HAS THE POTENTIAL TO REVOLUTIONIZE THE SMALL MOLECULE AND BIOLOGIC THERAPEUTIC INDUSTRIES BY ACCEL- ERATING STRUCTURE DETERMINATION STEPS, CURRENTLY A BOTTLENECK. FOR TELSAM TO REALIZE THIS POTENTIAL, ACADEMIC AND INDUSTRIAL STRUCTURE BIOLOGISTS NEED 1) EXPERIMENTALLY VALIDATED GUIDING PRINCIPLES FOR THE USE OF TELSAM, 2) A SUFFICIENT NUMBER OF SUCCESSFUL USE CASES TO DEMONSTRATE GENERAL EFFICACY, AND 3) DEMONSTRATION OF THE APPLICA- TIONS AND LIMITS OF TELSAM FUSION CRYSTALLIZATION. THUS FAR WE HAVE RIGOROUSLY INVESTIGATED THE GUIDING PRINCIPLES FOR TELSAM’S USE AND BEGUN TO DEMONSTRATE ITS USEFULNESS WITH PROTEINS RELEVANT IN HUMAN DISEASE. OUR GOALS FOR THE NEXT FIVE YEARS ARE TO RIGOROUSLY ADDRESS THE ABOVE THREE NEEDS AND BROADLY DISSEMINATE OUR FINDINGS TO THE STRUCTURAL BIOLOGY COMMUNITY. THE OVERALL VISION OF OUR RESEARCH PROGRAM IS FOCUSED ON PUSHING THE LIMITS OF PROTEIN ENGINEERING AND STRUCTURE DETERMINATION FIELDS WHILE AT THE SAME TIME DEVELOPING UNDERGRADUATE AND GRADUATE STUDENTS, INCLUDING THOSE FROM UNDERREPRESENTED BACKGROUNDS, INTO EXCELLENT BIOCHEMISTS. WE DO THIS BY PUTTING THEM AT THE FRONT LINES OF GROUNDBREAKING RESEARCH. BOTH UNDERGRADUATE AND GRADUATE STUDENTS IN OUR GROUP PARTICIPATE IN ALL PARTS OF SCIENTIFIC INQUIRY, INCLUDING REAGENT PREPARATION, EXPERIMENT DESIGN AND EXECUTION, DATA COLLECTION AND ANALYSIS, AND MANUSCRIPT PREPARATION AND PRESENTATION AT NATIONAL AND INTERNATIONAL MEETINGS. THE PROPOSED RESEARCH IS SIGNIFICANT BECAUSE IT WILL ACCELERATE THE SUCCESSFUL STRUCTURE DETERMINATION OF A GREATER NUMBER AND VARIETY OF BIOTECHNOLOGY AND DISEASE-RELEVANT PROTEINS, DRUGS, AND BIOLOGICS, ULTIMATELY LEADING TO NEW BIOTECHNOLOGY TOOLS, MORE EFFECTIVE DISEASE TREATMENTS, AND REDUCED HEALTHCARE COSTS.

MRI: ACQUISITION OF THE LANGUAGELENS FOR LARGE-SCALE LANGUAGE MODELING -MACHINE LEARNING IS REVOLUTIONIZING MANY PARTS OF SOCIETY, BUT TRAINING THE VERY BEST MODELS REQUIRES TREMENDOUS COMPUTING RESOURCES THAT ARE OFTEN OUT OF REACH FOR ACADEMIC GROUPS. THIS PROJECT THEREFORE ACQUIRES A SPECIAL-PURPOSE INSTRUMENT, NAMED THE LANGUAGELENS, THAT IS DESIGNED TO PROCESS VAST AMOUNTS OF NATURAL LANGUAGE TEXT. THE LANGUAGELENS WILL SUPPORT RESEARCH IN NATURAL LANGUAGE PROCESSING, DEEP LEARNING, COMPUTATIONAL LINGUISTICS, CRISIS INFORMATICS, CONVERSATIONAL AI, NEURAL MACHINE TRANSLATION, AND LEGAL CORPUS LINGUISTICS, AND WILL ENABLE ACADEMIC RESEARCH TO ADVANCE BOTH THE MACHINE LEARNING NEEDED TO TRAIN LARGE MODELS, AS WELL AS SOCIETIALLY RELEVANT APPLICATIONS OF THOSE MODELS. THE LANGUAGELENS IS A HIGH-PERFORMANCE GPU CLUSTER THAT BALANCES COMPUTE, STORAGE AND INTERNODE COMMUNICATION TO SUPPORT A VARIETY OF DEMANDING NLP-BASED WORKLOADS. THE LANGUAGELENS WILL BE FOCUSED ON SOLVING RESEARCH PROJECTS THAT HAVE THE POTENTIAL FOR TRANSFORMATIONAL, INTERDISCIPLINARY IMPACT ACROSS A WIDE VARIETY OF FIELDS. A KEY AREA OF FOCUS FOR THE INSTRUMENT IS THE ABILITY TO TRAIN NEW LARGE-SCALE LANGUAGE MODELS AND TO EXAMINE THEIR INNER WORKINGS IN REAL-TIME. LANGUAGE MODELS WILL BE TRAINED WITH SPECIFIC DOWNSTREAM APPLICATIONS IN MIND, ON NOVEL CORPORA AS WELL AS WITH NOVEL NEURO-SYMBOLIC ARCHITECTURES, TO HELP DERIVE INSIGHT FROM THE RESULTING WEIGHTS. THE LANGUAGELENS WILL PRIORITIZE SUPPORT FOR RESEARCH THAT ADDRESSES PRESSING SOCIETAL PROBLEMS. IT WILL ALSO PROVIDE AUTHENTIC WORKFORCE TRAINING AND EDUCATIONAL EXPERIENCES FOR STUDENTS: AS THE RESOURCE GAP BETWEEN INDUSTRY AND ACADEMIA GROWS, IT IS INCREASINGLY DIFFICULT TO GIVE THEM OPPORTUNITIES TO PURSUE HIGH-IMPACT RESEARCH THAT INVOLVES HUGE MODELS AND DATASETS. FINALLY, AS MANY COMPANIES REFUSE TO RELEASE THE PRETRAINED WEIGHTS OF THEIR MODELS, A CENTRAL GOAL IS TO MAKE TRAINED WEIGHTS FREELY AVAILABLE TO EVERYONE, SUBJECT TO ETHICAL CONSIDERATIONS, TO DRIVE NATIONAL IMPACT FOR BOTH INDUSTRY AND ACADEMIA. PROJECT RESOURCES SUCH AS CODE, PUBLICATIONS, DATASETS AND PRETRAINED MODELS WILL BE AVAILABLE THROUGH THE LANGUAGELENS WEBSITE AT HTTPS://LL.CS.BYU.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.

THRIVING IN A DIGITAL WORLD: EXAMINING TRAJECTORIES OF HEALTHY AND PROBLEMATIC MEDIA USE IN EARLY CHILDHOOD

COLLABORATIVE RESEARCH: QUANTIFYING CURRICULAR REASONING AS A CRITICAL PRACTICE IN TEACHING MATHEMATICS -TEACHERS OF MATHEMATICS ENGAGE IN CURRICULAR REASONING AS THEY DESIGN AND INTERACT WITH THEIR STUDENTS, CHOOSE CURRICULAR MATERIALS, AND IMPLEMENT CURRICULUM STANDARDS IN THE SERVICE OF HIGH-QUALITY INSTRUCTION. CURRENTLY, THERE IS NO SHARED MEASURE OF CURRICULAR REASONING OF MIDDLE SCHOOL TEACHER CLASSROOM DECISION MAKING IN MATHEMATICS. IN THIS RESEARCH PROJECT, THE TEAM DEVELOPS AND VALIDATES TWO MEASURES OF MIDDLE SCHOOL TEACHERS? CURRICULAR REASONING IN MATHEMATICS AS PRACTICED. THE FIRST MEASURE LOOKS AT CURRICULUM REASONING FROM THE PERSPECTIVE OF THE TEACHER, THE SECOND MEASURE ATTENDS TO THE PERSPECTIVES OF THE MATHEMATICS EDUCATION RESEARCH COMMUNITY. THE RESEARCH EXAMINES TEACHER SELF-ASSESSMENT COMPARED AND ALIGNED WITH THOSE OF PROFESSIONAL OBSERVERS (E.G., COACHES, SCHOOL LEADERS, AND RESEARCHERS) TO ESTABLISH THE VALIDITY OF THE TEACHER SELF-REPORT MEASURE. THE RESEARCH ESTABLISHES BENCHMARK SCORES OF TEACHERS CURRICULAR REASONING IN MIDDLE SCHOOL MATHEMATICS, SUPPORTING INCREASED INTERPRETABILITY AND UTILITY OF THE CURRICULAR REASONING SCORE TO IMPROVE CLASSROOM PRACTICE. THE RESEARCHERS CAREFULLY EXAMINE FOUR RESEARCH QUESTIONS: [1] TO WHAT EXTENT DOES VALIDITY EVIDENCE SUPPORT USE OF THE CURRICULAR REASONING SELF-ASSESSMENT SURVEY SUITE FOR MIDDLE SCHOOL MATHEMATICS TEACHERS TO MEASURE THEIR OWN CURRICULAR REASONING? [2] TO WHAT EXTENT DOES VALIDITY EVIDENCE SUPPORT USE OF THE CURRICULAR REASONING OBSERVATION ASSESSMENT TO MEASURE MIDDLE SCHOOL MATHEMATICS TEACHERS? CURRICULAR REASONING? [3] IS THERE A SIGNIFICANT RELATIONSHIP BETWEEN MIDDLE SCHOOL MATHEMATICS TEACHERS? CURRICULAR REASONING WHEN MEASURED BY THE NEW CURRICULAR REASONING TOOLS? [4] WHAT BENCHMARKS DEFINE DIFFERENT CURRICULAR REASONING LEVELS ON EACH OF THE TWO MEASURES? THE RESEARCH TEAM GATHERS VALIDITY DATA BASED ON SHARED STANDARDS HELD BY THE AMERICAN PSYCHOLOGICAL ASSOCIATION, THE NATIONAL COUNCIL ON MEASUREMENT IN EDUCATION, AND THE AMERICAN EDUCATIONAL RESEARCH ASSOCIATION. THE RESEARCH ADVANCES OUR UNDERSTANDING OF TEACHER CURRICULAR REASONING THROUGH THE DEVELOPMENT OF THE TWO MEASURES. THE WORK BRIDGES RESEARCH AND PRACTICE AS THE RESEARCHERS USE SELF-REPORT AND OBSERVATIONAL EVIDENCE TO SUPPORT AND IMPROVE TEACHERS? PRACTICE OF CURRICULAR REASONING. THE TEAM USES RASCH PSYCHOMETRIC TOOLS FOR STANDARD SETTING TO IMPROVE THE USABILITY OF THE MEASURES FOR CLASSROOM USAGE. THE DISCOVERY RESEARCH PREK-12 PROGRAM (DRK-12) SEEKS TO SIGNIFICANTLY ENHANCE THE LEARNING AND TEACHING OF SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) BY PREK-12 STUDENTS AND TEACHERS, THROUGH RESEARCH AND DEVELOPMENT OF INNOVATIVE RESOURCES, MODELS, AND TOOLS. PROJECTS IN THE DRK-12 PROGRAM BUILD ON FUNDAMENTAL RESEARCH IN STEM EDUCATION AND PRIOR RESEARCH AND DEVELOPMENT EFFORTS THAT PROVIDE THEORETICAL AND EMPIRICAL JUSTIFICATION FOR PROPOSED PROJECTS.? THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

3D TEMPERATURE CONTROL TO STUDY BIOLOGICAL PROCESSES

MECHANISMS OF CHAPERONE-MEDIATED FOLDING OF BETA-PROPELLER PROTEINS ESSENTIAL FOR VISION. - PROJECT SUMMARY THE CYTOSOLIC CHAPERONIN CCT IS A LARGE PROTEIN COMPLEX THAT PLAYS AN INDISPENSABLE ROLE IN MAINTAINING THE CELLULAR PROTEOME BY ASSISTING IN THE FOLDING OF NUMEROUS PROTEINS WITH COMPLEX TERTIARY STRUCTURES AND UNFAVORABLE FOLDING TRAJECTORIES. PROPER CCT FUNCTION IS VITAL TO HUMAN VISION AS EVIDENCED BY THE FACT THAT INACTIVATING MUTATIONS IN CCT CAUSE LEBER CONGENITAL AMAUROSIS (LCA). CCT CONTRIBUTES TO THE VISUAL PROCESS BY FOLDING THE CYTOSKELETAL PROTEINS ACTIN AND TUBULIN AS WELL AS OTHER PROTEINS WITH B-PROPELLER FOLDS THAT HAVE ESSENTIAL FUNCTIONS IN VISON. THESE INCLUDE THE G PROTEIN B1 (GB1) SUBUNIT OF THE VISUAL G PROTEIN TRANSDUCIN, THE G PROTEIN B5 (GB5) SUBUNIT OF THE REGULATOR OF G PROTEIN SIGNALING 9 (RGS9) DIMER, AND THE BBS2 AND BBS7 SUBUNITS OF THE BARDET-BIEDL SYNDROME (BBS) CILIARY TRANSPORT COMPLEX, THE BBSOME. DESPITE THE IMPORTANCE OF CCT IN MAINTAINING THE PROTEOME, WE KNOW VERY LITTLE AT THE MOLECULAR LEVEL ABOUT HOW CCT ASSISTS IN THE FOLDING OF THESE B-PROPELLER PROTEINS AND HOW MUTATIONS DISRUPT FOLDING AND CAUSE DISEASE. TO ADDRESS THIS GAP IN KNOWLEDGE, WE PROPOSE TO DETERMINE THE STRUCTURES OF HUMAN GB1 AND GB5 AND THEIR DISEASE-CAUSING MUTANTS. STRUCTURES OF GB5 BOUND TO CCT AND ITS CO-CHAPERONE PHLP1 SHOW PROGRESSIVE STEP-BY-STEP FORMATION OF THE GB5 B-PROPELLER THAT REVEALS ITS FOLDING TRAJECTORY. UNRAVELING HOW CCT INFLUENCES THE FOLDING TRAJECTORY OF A B-PROPELLER PROTEIN REPRESENTS A BREAKTHROUGH IN UNDERSTANDING CHAPERONE-MEDIATED PROTEIN FOLDING. MOREOVER, APPLYING THESE SAME TECHNIQUES TO MISFOLDING AND DISEASE-CAUSING MUTANTS OF GB1 AND GB5 WILL SHOW HOW THE MUTATIONS DISRUPT THEIR FOLDING TRAJECTORIES. FINALLY, WE PROPOSE TO EMPLOY OUR BIOCHEMICAL AND HIGH RESOLUTION CRYO-EM EXPERTISE TO UNDERSTANDING BIOGENESIS OF THE BBSOME COMPLEX. A KEY STEP IN BBSOME ASSEMBLY IS THE FORMATION OF THE BBS2-BBS7 DIMER, WHICH REQUIRES BOTH CCT AND THREE CHAPERONIN- LIKE (CL-BBS) PROTEINS BBS6, BBS10 AND BBS12 TO COME TOGETHER. DESPITE THE 18 YEARS SINCE CL-BBS PROTEIN DISCOVERY AND THE PREDOMINANT ROLE THEIR MUTATIONS PLAY IN CAUSING BBS, THE MOLECULAR MECHANISM BY WHICH THE CL-BBS PROTEINS AND CCT ASSIST IN BBS2 AND BBS7 FOLDING AND BBS2-BBS7 DIMER FORMATION IS UNKNOWN. THE PROPOSED STUDIES WILL FILL THIS GAP IN KNOWLEDGE AND WILL DEEPEN UNDERSTANDING OF THE MOLECULAR DEFECTS CAUSED BY MUTATIONS IN GB SUBUNITS, BBS7 AND CL-BBS PROTEINS. THE STRUCTURAL WORK WILL ESTABLISH A FOUNDATION FOR TARGETED, STRUCTURE-BASED DRUG DESIGN TO CREATE NEW THERAPIES FOR THE RETINOPATHIES, NEUROPATHIES AND CILIOPATHIES CAUSED BY THESE MUTATIONS.

VENTRAL TEGMENTAL AREA GABA NEURONS: PLASTICITY & OPIATE RECEPTORS AT INHIBITORY INPUTS

TRACKING INTERGRANULAR STRAIN DYNAMICS WITH NEAR-ATOMIC SCALE COHERENT X-RAY IMAGING AT NEXT GENERATION LIGHT SOURCES

FISCAL YEAR 2024 CONSOLIDATED INNOVATIVE NUCLEAR RESEARCH. UNIVERSITY NAME: BRIGHAM YOUNG UNIVERSITY

DEVELOPING A CRISPR-BASED FORWARD-GENETIC SCREENING METHOD IN EMBRYONIC ZEBRAFISH

RUI: COLLABORATIVE RESEARCH: NETWORK CLUSTER: DUST IN THE CRITICAL ZONE FROM THE GREAT BASIN TO THE ROCKY MOUNTAINS

RAGE TARGETING ATTENUATES SMOKE-INDUCED INFLAMMATION

2022-2026 CENTER FOR INTERNATIONAL BUSINESS EDUCATION GRANT