PURDUE UNIVERSITY

GRANT PROGRAM

GRANT PROGRAM

NEW START COOPERATIVE AGREEMENT TITLED: ENERGETICS MATERIALS BASIC RESEARCH CENTER

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** BLUE FOOD (SEAFOOD) CAN PROVIDE MORE NUTRITIONAL BENEFITS AND BE PRODUCED MORE SUSTAINABLY THAN LAND-BASED FOODS; HOWEVER, APPROXIMATELY 90% OF SEAFOOD CONSUMED IN THE US COMES FROM ABROAD, RESULTING IN $17B TRADE DEFICIT. AQUAPONICS INTENSIVELY PRODUCES A DIVERSE ARRAY OF NUTRITIOUS BLUE FOODS AND SPECIALTY CROPS, BUT THIS EMERGING FOOD PRODUCTION SYSTEM FACES INTERTWINED TECHNICAL, ECONOMIC, AND ENVIRONMENTAL CHALLENGES THAT ARE THE MAIN BARRIERS TO ITS WIDE ADOPTION. THE OVERARCHING HYPOTHESES OF THIS PURDUE UNIVERSITY-LED PROJECT ARE: 1) INTEGRATING AQUAPONICS WITH MICROALGAE CULTIVATION, ANAEROBIC DIGESTION AND BIOREFINING CAN FULLY UTILIZE NUTRIENTS AND PRODUCE ENERGY AND HIGH-VALUE BIOPRODUCTS; AND, 2) INTEGRATING RESEARCH WITH EXTENSION AND EDUCATION WILL INCREASE ADOPTION OF AQUAPONICS AND CONSUMER WILLINGNESS TO PURCHASE BLUE FOODS. SPECIFIC PROJECT OBJECTIVES INCLUDE: 1) IDENTIFYING BARRIERS AND OPPORTUNITIES FOR BLUE FOOD AND AQUAPONICS; 2) BUILDING A NOVEL, INTEGRATED, AQUAPONICS FOOD PRODUCTION SYSTEM; 3) DEVELOPING MULTI-DIMENSIONAL SUSTAINABILITY METRICS FOR SYSTEM ASSESSMENT AND MANAGEMENT; 4) SUPPORT AQUAPONICS AND BLUE FOOD INDUSTRY AND MARKET DEVELOPMENT; AND, 5) CREATING BLUE FOOD-RELATED EDUCATION MATERIALS. THIS PROJECT IS EXPECTED TO BUILD A ZERO-WASTE, GRID-INDEPENDENT, AND ECONOMICALLY VIABLE FOOD PRODUCTION SYSTEM, AND GENERATE AN EVIDENCE-BASED VISION AND FRAMEWORK FOR FACILITATING THE ADOPTION OF AQUAPONICS. THIS NOVEL INTEGRATED AQUAPONICS SYSTEM CAN INCREASE LOCAL AND REGIONAL PRODUCTION OF ADEQUATE, NUTRITIOUS, AND AFFORDABLE BLUE FOODS WITH A MINIMAL ENVIRONMENTAL FOOTPRINT, ULTIMATELY DIVERSIFYING US AGRICULTURAL SYSTEMS AND DIETARY PATTERNS.

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** FORESTS PROVIDE MANY BENEFITS, SUCH AS TIMBER AND FIBER PRODUCTION AND CARBON SEQUESTRATION, BUT THEIR LONG-TERM SUSTAINABILITY IS INCREASINGLY THREATENED BY VARIOUS CHANGES SUCH AS INSECT OUTBREAKS, EXTREME WEATHER, EVOLVING MARKETS AND LAND-USE CHANGES. MORE DETAILED AND ACCURATE INFORMATION IS NEEDED TO ALLOW LANDOWNERS, MANAGERS AND POLICYMAKERS TO MAKE ECONOMICAL AND DATA-DRIVEN DECISIONS THAT WILL AFFECT THE DELIVERY, SUSTAINABILITY AND RESILIENCE OF FOREST RESOURCES. THE GOAL OF THE PROMOTING ECONOMIC RESILIENCE AND SUSTAINABILITY OF THE EASTERN U.S. FORESTS (PERSEUS) PROJECT IS TO PROVIDE SOUND SCIENCE, OUTREACH AND EDUCATIONAL OPPORTUNITIES THAT LAY THE FOUNDATION FOR A MAJOR FUNDAMENTAL CHANGE IN FORESTRY. MORE SPECIFICALLY, PERSEUS AIMS TO (1) CREATE A SET OF DIGITAL TOOLS AND WALL-TO-WALL FOREST MAPPING PRODUCTS THAT WILL PROVIDE DETAILED AND NEAR REAL-TIME MEASUREMENTS, (2) BUILD AND APPLY A FRAMEWORK TO VISUALLY REPRESENT CURRENT AND FUTURE FOREST TRENDS, (3) ENGAGE WITH STAKEHOLDERS TO DEVELOP DATA-DRIVEN MANAGEMENT PRACTICES, AND (4) ESTABLISH EDUCATIONAL AND TRAINING PROGRAMS THAT SUPPORT STUDENTS AND PROFESSIONALS IN UNDERSTANDING AND MAKING USE OF DIGITAL TECHNOLOGIES. PERSEUS WILL PROVIDE A FOUNDATION FOR REDEFINING FOREST INVENTORY IN THE UNITED STATES WHILE ALSO PROVIDING THE MUCH-NEEDED ABILITY TO PREDICT FUTURE FOREST CONDITIONS. WORKING WITH STAKEHOLDERS, PERSEUS WILL PROVIDE (1) USER-FRIENDLY TOOLS AND PROGRAMS TO BETTER MEASURE AND MONITOR FORESTS LIKE NEVER BEFORE, (2) SUSTAINABLE FOREST MANAGEMENT PRACTICES, AND (3) A PLATFORM TO OPTIMIZE REGIONAL EFFORTS IN BUILDING ENVIRONMENTALLY AND ECONOMICALLY SUSTAINABLE FORESTS, ESPECIALLY ON PRIVATE LANDS IN THE RURAL UNITED STATES. MOREOVER, THE PROJECT WILL TRAIN COHORTS OF STUDENTS AND PROFESSIONALS TO BUILD A DIGITALLY COMPETENT WORKFORCE. SUCCESSFUL COMPLETION OF THE PROJECT WILL INCREASE PHYSICAL GOODS SUCH AS FOOD, WATER, FUEL AND TIMBER PROVIDED BY FOREST ECOSYSTEMS, AND IMPROVE OPERATIONAL EFFICIENCY IN FORESTS ACROSS THE EASTERN UNITED STATES. IN PARTICULAR, MEASUREMENT TOOLS DEVELOPED BY PERSEUS WILL MODERNIZE AND INFORM FOREST MANAGEMENT BY CREATING DIGITAL INVENTORY TOOLS THAT EMPOWER STAKEHOLDERS TO BETTER UNDERSTAND THE POTENTIAL IMPACTS OF THEIR DECISIONS ON A LOCAL AND REGIONAL SCALE. THE RESULTING FRAMEWORK WILL PROVIDE A DIGITAL BRIDGE, ENABLING LANDOWNERS AND STAKEHOLDERS WITH PRACTICAL TACTICS AND FOREST SIMULATION TO INFORM DECISION- AND POLICY-MAKING. COMPLEMENTING THIS, THE DIGITAL FORESTRY EDUCATIONAL PROGRAMS DEVELOPED BY PERSEUS WILL GENERATE A WORKFORCE CAPABLE OF CARRYING AND OPTIMIZING THESE TOOLS INTO THE FUTURE.

EXTENSION DELIVERS PRACTICAL RESEARCH-BASED INFORMATION VIA EDUCATION THAT TRANSFORMS LIVES/LIVELIHOODS OF INDIVIDUALS AND COMMUNITIES. WE AIM TO BE THE EDUCATION PARTNER FOR LIFE-LONG LEARNING. PROGRAMS BENEFIT YOUTH, ADULT VOLUNTEERS, FAMILIES, FARMERS/RANCHERS, LANDOWNERS, BUSINESSES/ORGANIZATIONS, GOVERNMENT OFFICIALS, AND COMMUNITIES. WE CULTIVATE ENGAGEMENT FOR ALL INDIVIDUALS TO FULLY PARTICIPATE, CONTRIBUTE AND THRIVE. WE PROMOTE ENTREPRENEURSHIP BY STRENGTHENING PRACTICES, PRODUCTS, MARKETS AND ENGAGING COLLABORATIONS. 1-CLIMATE CHANGE, NATURAL RESOURCES, SUSTAINABLE ENERGY ACTIVITIES A) DEVELOP ADAPTATION/MITIGATION FOR EXTREME WEATHER; B) DETERMINE CROP VARIETIES, CLIMATE-SMART PRACTICES AND ANIMAL SYSTEMS TO CONSERVE NATURAL RESOURCES AND REDUCE GREENHOUSE GAS; C) INCREASE BIOENERGY/BIOFUELS RESEARCH AND ADOPTION, AND CONSERVATION PRACTICES FOR NATURAL RESOURCES. WE SUPPORT 3 JOINT AGRONOMIST POSITIONS TO HELP FARMERS ADOPT CONSERVATION APPLICATIONS AND SUSTAINABLE AG. CONSERVATION THROUGH COMMUNITY LEADERSHIP TRAINS LEADERS, GOVERNMENT OFFICIALS, NGO REPRESENTATIVES AND RESIDENTS FOR NATURAL RESOURCE CONSERVATION DECISION-MAKING. 2-WORKFORCE DEVELOPMENT ACTIVITIES A) SUPPORT WORKERS TO OBTAIN AG JOB CERTIFICATIONS; B) DEVELOP STEM SKILLS AND AG TECHNOLOGIES; C) TRAIN BEGINNING FARMERS/RANCHERS FOR OPERATION VIABILITY AND TO RAISE STEM CAREER INTERESTS. WE JOIN RESOURCES, EXPERTISE AND NETWORKING TO STRENGTHEN WORKFORCE EDUCATION, TECHNOLOGY ADOPTION AND MANUFACTURING RESEARCH. WORK READY TRAINS YOUTH HOW TO GET JOBS AND BUILD MARKETABLE SKILLS. 3-POSITIVE YOUTH DEVELOPMENT <(>&<)> 4-H ACTIVITIES A) BUILD POSITIVE LIFE AND SOCIAL-EMOTIONAL SKILLS; B) TRAIN NEW STEM SKILLS; C) DEVELOP SKILLS/ATTITUDES/BEHAVIORS FOR YOUTH TO THRIVE AS POSITIVE, CONTRIBUTING COMMUNITY MEMBERS. SPARK AND 4-H CLUB PROGRAMS ARE OPPORTUNITIES FOR NEW AUDIENCES AND COMMUNITIES. 4-BIG DATA, INTERNET OF THINGS, BROADBAND ACCESS, DIGITAL LITERACY, INCLUSION <(>&<)> INNOVATION ACTIVITIES A) DEVELOP DIGITAL AG DATA SCIENCE TOOLS FOR EFFICIENT OPERATIONS; B) ADVANCE AG TECHNOLOGIES-UAVS, MODELING, SENSORS, ROBOTICS, AUTOMATION, AUTONOMOUS; C) ENSURE DIGITAL PARITY/INCLUSION/EQUITY OF FAMILIES, FARMS, RURAL HOUSEHOLDS, BUSINESSES, COMMUNITIES. DIGITAL READY BUSINESS ADVANCES SMALL BUSINESS CAPACITY AND STRENGTHENS BROADBAND APPLICATION. 5-HUMAN, FAMILY <(>&<)> COMMUNITY HEALTH ACTIVITIES A) SUPPORT FARMERS DEALING WITH STRESS, ENCOURAGE ADOPTION OF QUALITY-OF-LIFE PRACTICES; B) HELP BUILD RESILIENT, INCLUSIVE, AND SUSTAINABLE COMMUNITIES, ENHANCE FOOD ACCESS AND ACTIVE LIVING; C) ENSURE POLICIES/SYSTEMS/ENVIRONMENTS FOR QUALITY OF LIFE. WE OFFER TRAINING FOR MENTAL HEALTH PROVIDERS, SUICIDE PREVENTION CALL CENTERS, AND WOMEN IN AG. CREATING HEALTHY COMMUNITIES FOR DECISION-MAKERS AND LOCAL LEADERS OF PARK BOARDS OR PLANNING COMMISSIONS INVOLVES PUBLIC DELIBERATION TO DESIGN PLANS FOR SUSTAINABLE IMPROVEMENTS. 6-FOOD PRODUCTION, SECURITY <(>&<)> SAFETY ACTIVITIES A) ADDRESS INVASIVE SPECIES AND INTEGRATED PEST/WEED/DISEASE MANAGEMENT; B) SUPPORT AG MANAGEMENT, MULTIDISCIPLINARY FARM DECISION-MAKING, SUSTAINABLE PRE- AND POST-HARVEST PRACTICES, AND EFFICIENT ON- AND OFF-FARM PRODUCTION; C) STRENGTHEN WHOLE VALUE CHAIN, MARKETS. RESEARCH AND EXTENSION ON TAR SPOT IN CORN IDENTIFY, MONITOR AND CONTAIN THE DISEASE. WE TEACH VEGETABLE PRODUCTION FOOD SAFETY PRACTICES TO COMBAT SALMONELLA OUTBREAKS. PROGRAMS ADDRESS RISK ASSESSMENTS, COMMODITY MARKETING, LAND LEASES, MARKETING, AND SUCCESSION PLANS. 7-URBAN AG <(>&<)> URBAN EXTENSION ACTIVITIES A) BUILD SKILLS FOR CROP/PRODUCE/ANIMAL PRODUCTION AND URBAN SITE PREPARATION; B) STRENGTHEN COMMUNITIES WITH URBAN GARDENS AND FARMERS MARKETS; C) ENCOURAGE POLICIES/SYSTEMS/ENVIRONMENTS FOR COLLECTIVE IMPACT. GRASS TO GARDEN TEACHES RESIDENTS, VOLUNTEERS, NON-PROFITS, LOCAL OFFICIALS, AND GARDENERS TO START COMMUNITY-BASED GARDENS TO IMPROVE LOCAL FOOD ACCESS. THERE ARE NO KNOWN SUBRECIPIENT ACTIVITIES.

EXTENSION DELIVERS PRACTICAL RESEARCH-BASED INFORMATION VIA EDUCATION THAT TRANSFORMS LIVES/LIVELIHOODS OF INDIVIDUALS <(>&<)> COMMUNITIES. WE AIM TO BE THE EDUCATION PARTNER FOR LIFE-LONG LEARNING. PROGRAMS BENEFIT YOUTH, ADULT VOLUNTEERS, FAMILIES, FARMERS/RANCHERS, LANDOWNERS, BUSINESSES/ORGANIZATIONS, GOVERNMENT OFFICIALS <(>&<)> COMMUNITIES. WE PROMOTE ENTREPRENEURSHIP BY STRENGTHENING PRACTICES, PRODUCTS, MARKETS <(>&<)> ENGAGING COLLABORATIONS. 1-NATURAL RESOURCES ACTIVITIES A) DEVELOP ADAPTATION <(>&<)> MITIGATION STRATEGIES FOR WEATHER VARIABILITY <(>&<)> EXTREME EVENTS; B) CONSERVE SOIL <(>&<)> WATER THROUGH IMPROVED PRACTICES <(>&<)> SYSTEMS; C) MANAGE INVASIVE SPECIES <(>&<)> SUPPORT POLLINATOR HEALTH; D) DEVELOP <(>&<)> ADOPT SUSTAINABLE AGRICULTURAL PRACTICES, RESILIENT CROPS <(>&<)> SEQUESTERING CARBON THROUGH AGRICULTURE; E) RESEARCH ENERGY SOURCES, ENERGY-EFFICIENT PROCESSES, PRODUCTS <(>&<)> AGRICULTURAL MACHINES. CONSERVATION THROUGH COMMUNITY LEADERSHIP TRAINS LEADERS, GOVERNMENT OFFICIALS, NGO REPRESENTATIVES <(>&<)> RESIDENTS FOR NATURAL RESOURCE CONSERVATION DECISION-MAKING. 2-WORKFORCE DEVELOPMENT ACTIVITIES A) SUPPORT WORKERS IN OBTAINING CER TIFICATIONS, LICENSES, <(>&<)> CONTINUING EDUCATION; B) PREPARE YOUTH <(>&<)> ADULTS WITH JOB READINESS <(>&<)> TECHNICAL SKILLS; C) STRENGTHEN STEM EDUCATION FOR AGRICULTURAL <(>&<)> ENVIRONMENTAL CAREERS; D) TRAIN BEGINNING FARMERS <(>&<)> RANCHERS FOR VIABLE OP ERATIONS; E) EXPAND OPPORTUNITIES FOR CAREER PREPARATION <(>&<)> LIFELONG LEARNING. WORK READY TRAINS YOUTH HOW TO GET JOBS <(>&<)> BUILD MARKETABLE SKILLS. 3-POSITIVE YOUTH DEVELOPMENT <(>&<)> 4-H OPPORTUNITIES ACTIVITIES A) BUILD POSITIVE LIFE <(>&<)> SOCIAL-EMOTIONAL SKILLS; B) DEVELOP STEM, LEADERSHIP, CIVIC ENGAGEMENT <(>&<)> HEALTHY LIFESTYLE SKILLS; C) PREPARE YOUTH FOR COLLEGE <(>&<)> CAREER READINESS; D) PROVIDE OPPORTUNITIES THROUGH 4-H CLUBS, SPARK CLUBS, CAMPS, <(>&<)> VOLUNTEER TRAINING. SPARK <(>&<)> 4-H CLUB PROGRAMS ARE OPPORTUNITIES FOR NEW AUDIENCES <(>&<)> COMMUNITIES. 4-AGRICULTURAL <(>&<)> DIGITAL TECHNOLOGY <(>&<)> INNOVATION ACTIVITIES A) DEVELOP DIGITAL AGRICULTURE TOOLS, MODELS, <(>&<)> DECISION-SUPPORT SYSTEMS; B) EXPAND TECHNOLOGIES INCLUDING UAVS, SENSORS, ROBOTICS, AUTOMATION <(>&<)> AI; C) INCREASE BROADBAND ACCESS <(>&<)> DIGITAL LITERACY FOR FARMS, FAMILIES <(>&<)> BUSINESSES; D) SUPPORT DIGITAL READINESS FOR RURAL HOUSEHOLDS <(>&<)> SMALL BUSINESSES. DIGITAL READY BUSINESS ADVANCES SMALL BUSINESS CAPACITY <(>&<)> STRENGTHENS BROADBAND APPLICATION. 5-HUMAN, FAMILY, <(>&<)> COMMUNITY HEALTH ACTIVITIES A) SUPPORT MENTAL <(>&<)> PHYSICAL HEALTH THROUGH STRESS MANAGEMENT, NUTRITION <(>&<)> ACTIVE LIVING; B) ADDRESS HEALTH CHALLENGES SUCH AS OBESITY, OPIOID ADDICTION <(>&<)> DEPRESSION; C) STRENGTHEN FINANCIAL RESOURCE MANAGEMENT, LEADERSHIP <(>&<)> PUBLIC DECISION-MAKING; D) ENHANCE COMMUNITY VITALITY THROUGH COALITIONS <(>&<)> PROGRAMS THAT IMPROVE QUALITY OF LIFE. WE OFFER TRAININGS TO MENTAL HEALTH PROVIDERS, SUICIDE PREVENTION CALL CENTERS <(>&<)> FOOD HANDLERS. 6-FOOD PRODUCTION, SECURITY <(>&<)> SAFETY ACTIVITIES A) ADVANCE SUSTAINABLE PLANT <(>&<)> ANIMAL PRODUCTION SYSTEMS; B) IMPROVE NUTRIENT, SOIL <(>&<)> WATER MANAGEMENT; C) ADDRESS INVASIVE SPECIES <(>&<)> SUPPORT INTEGRATED PEST, WEED <(>&<)> DISEASE MANAGEMENT; D) STRENGTHEN FOOD SAFETY PRACTICES THROUGH DETECTION, HANDLING, TRACEABILITY <(>&<)> MONITORING; E) BUILD VALUE CHAINS <(>&<)> MARKETS THAT CONNECT FARMS TO CONSUMERS. CREATING HEALTHY COMMUNITIES FOR DECISION-MAKERS <(>&<)> LOCAL LEADERS OF PARK BOARDS OR PLANNING COMMISSIONS INVOLVES PUBLIC DELIBERATION TO DESIGN PLANS FOR SUSTAINABLE IMPROVEMENTS. 7- GARDENING, SPECIALTY CROPS <(>&<)> SMALL-SCALE FARMING ACTIVITIES A) EXPAND SKILLS FOR GARDENING, SPECIALTY CROPS <(>&<)> SMALL-SCALE FARMING INCLUDING AQUAPONICS, HYDROPONICS <(>&<)> CONTROLLED ENVIRONMENTS; B) STRENGTHEN LOCAL FOOD ACCESS <(>&<)> COMMUNITY VITALITY THROUGH GARDENING <(>&<)> MARKETS; C) PROMOTE REGENERATIVE <(>&<)> DIVERSIFIED FARMING SYSTEMS; D) ENCOURAGE COMMUNITY IMPACT THROUGH PROGRAMS THAT SUPPORT LOCAL FOOD SYSTEMS. GRASS TO GARDEN TEACHES RESIDENTS, VOLUNTEERS, NON-PROFITS, LOCAL OFFICIALS <(>&<)> GARDENERS TO START COMMUNITY-BASED GARDENS TO IMPROVE LOCAL FOOD ACCESS.

QUANTUM PHOTONIC INTEGRATED DESIGN CENTER (QUPIDC)

DEVELOPMENT AND DEMONSTRATION OF AN INDUSTRIAL HYDROGEN-FIRED STEEL REHEATING FURNACE

THIS PROJECT PROPOSES A NATIONWIDE COLLABORATION BETWEEN INDUSTRY AND ACADEMIA TO PIONEER AN INDUSTRIAL-SCALE DEMONSTRATION OF ALTERNATIVE INJECTANT REFINING AND ELECTRO-MAGNETIC STIRRING (EMS) ELECTRIC ARC FURNACE (EAF) OPERATION IN THE U.S. AND CREATE A LANDMARK EXAMPLE FOR RELEVANT INDUSTRIAL PRACTICES WORLD-WIDE USING STATE-OF-THE-ART CFD MODELS, (LIFE-CYCLE ASSESSMENT) LCA & (TECHNO-ECONOMIC ASSESSMENT) TEA, LABORATORY TESTING, AND INDUSTRIAL DEMONSTRATION. THE PROPOSED RESEARCH REFLECTS A JOINT EXPLORATORY R&D EFFORT BETWEEN ACADEMIA AND INDUSTRY TO ENABLE COMPLETE DECARBONIZATION OF THE EAF PROCESS. WHEN COMPLETED, THE PROJECT WILL DEMONSTRATE THE FEASIBILITY OF REPLACING FOSSIL-CARBON USE IN THE EAF WITH ALTERNATIVE INJECTANTS TO REDUCE SCOPE ONE CO2 EMISSIONS WHILE MAINTAINING EXISTING QUALITY AND PRODUCTIVITY STANDARDS.

PURPOSE: THE LONG-TERM GOAL OF THIS PROJECT IS TO PROVIDE THE OUTREACH EXPERTISE NECESSARY TO TRANSFER GLNPO SPONSORED RESEARCH AND MONITORING DATA AND LEGACY PROGRAMS TO CLIENTS THAT CAN APPLY THIS KNOWLEDGE TO ENHANCE DECISION MAKING FOR IMPROVED GREAT LAKES ECOSYSTEMS AND WATER QUALITY. ACTIVITIES TO BE PERFORMED: THE OBJECTIVES OF THIS PROJECT WILL CONTINUE THE ONGOING FORMAL PARTNERSHIP BETWEEN U.S. EPA AND IISGCP IN THREE MAJOR AREAS: 1. COASTAL REMEDIATION AND REVITALIZATION: IISGCP WILL CONTINUE TO HELP GLNPO ENGAGE COMMUNITIES THROUGHOUT THE GREAT LAKES LEGACY ACT (GLLA) CLEANUP PROCESS AND WILL WORK TO FACILITATE REVITALIZATION. 2. GREAT LAKES SCIENCE AND MONITORING: IISGCP WILL CONTINUE WORKING WITH GLNPO TO MAXIMIZE THE IMPACT OF MONITORING DATA THROUGH APPLICATIONS SUCH AS GREATLAKESMONITORING.ORG, APPLIED RESEARCH TO EXPAND THE BREADTH OF GLNPO MONITORING AND COORDINATION OF THE COORDINATED SCIENCE AND MONITORING INITIATIVE (CSMI). 3. GREAT LAKES LITERACY: CGLL WAS

FIREFLY: A CYBER-PHYSICAL FRAMEWORK FOR SCALABLE CPS MODELING AND SIMULATION

PURDUE'S COLLEGE OF AGRICULTURE'S 2021-2026 STRATEGIC PLAN OUTLINES THE VISION AND MISSION: TO EMBODY THE IDEAL OF A CONTEMPORARY LAND-GRANT MISSION TO PREPARE TOMORROW'S LEADERS FOR MEETING SOCIETY'S NEEDS, AND TO ACHIEVE WORLDWIDE LEADERSHIP IN GROWING A SUSTAINABLE FUTURE BY ADDRESSING CHALLENGES IN FOOD, LIFE AND NATURAL RESOURCE SCIENCES, WORKING ACROSS DISCIPLINES. HATCH FUNDING FROM THE USDA NATIONAL INSTITUTE FOR FOOD AND AGRICULTURE (NIFA) ENABLES PURDUE'S COLLEGE OF AGRICULTURE (COA) TO ACCOMPLISH ITS STRATEGIC PLAN THROUGH A BROAD PORTFOLIO OF RESEARCH ACROSS THREE UNITS ON THE WEST LAFAYETTE CAMPUS. PURDUE FACULTY IN THE COA, COLLEGE OF VETERINARY MEDICINE, AND SELECTED DEPARTMENTS IN THE COLLEGE OF HEALTH AND HUMAN SCIENCES WHO HAVE RESEARCH APPOINTMENTS FUNDED AT 20% OR MORE BY FORMULA FUNDS ARE REQUIRED TO SUBMIT A FIVE-YEAR PLAN OF RESEARCH. THESE HATCH PROJECTS INCLUDE BOTH FIELD- AND LABORATORY-BASED RESEARCH (FUNDAMENTAL AND APPLIED) THAT DIRECTLY CONNECT WITH CRITICAL ISSUES CREATED TO INCORPORATE COA INITIATIVES, AND TO ALIGN WITH PRIORITIES OF NIFA, RESEARCH, EDUCATION <(>&<)> ECONOMIC GOALS OF USDA, AGRICULTURE <(>&<)> FOOD RESEARCH INITIATIVE, FOUNDATION FOR FOOD <(>&<)> AGRICULTURE RESEARCH, AND EXTENSION COMMITTEE ON ORGANIZATION <(>&<)> POLICY. CRITICAL ISSUES ARE CLIMATE CHANGE, NATURAL RESOURCES AND THE ENVIRONMENT, AND SUSTAINABLE ENERGY; WORKFORCE DEVELOPMENT; POSITIVE YOUTH DEVELOPMENT AND 4-H OPPORTUNITIES; BIG DATA, INTERNET OF THINGS, BROADBAND ACCESS, DIGITAL LITERACY, INCLUSION, AND INNOVATION; HUMAN, FAMILY, AND COMMUNITY HEALTH; FOOD PRODUCTION, SECURITY, AND SAFETY; AND URBAN AGRICULTURE AND URBAN EXTENSION. THE PORTFOLIO OF PROJECTS INCLUDES ECONOMIC RESEARCH, PLANT AND ANIMAL GENETIC AND BREEDING, SUSTAINABLE AGRICULTURAL PRACTICES INCLUDING COVER CROPS AND OTHER MANAGEMENT PRACTICES TO REDUCE FARM INPUTS WHILE INCREASING PRODUCTIVITY, MOLECULAR BIOCHEMICAL APPROACHES TO UNDERSTAND PLANT TRAITS AND HUMAN NUTRITION, SOCIAL SCIENCE OF RURAL AND MIGRANT COMMUNITIES, AND TECHNOLOGICAL ADVANCES TO QUICKLY DETECT THE PRESENCE OF PATHOGENS IN PRODUCE, TO NAME A FEW. PURDUE'S AGRICULTURAL CENTERS (PACS) AND AGRONOMY CENTER FOR RESEARCH AND EDUCATION (ACRE) ARE VALUABLE RESOURCES FOR AGRICULTURAL RESEARCHERS FROM VARIOUS DISCIPLINES THE PACS ARE LOCATED STRATEGICALLY ACROSS INDIANA, THESE CENTERS OFFER DIVERSE LAND AND SOIL TYPES, AND MICROCLIMATES, ALLOWING SCIENTISTS TO CONDUCT RESEARCH IN REAL-WORLD CONDITIONS. ACRE IS LOCATED NEAR THE MAIN CAMPUS. BOTH THE PACS AND ACRE OFFER UNIQUE ADVANTAGES TO SCIENTISTS WITH LARGE PLOT RESEARCH FOR FIELD-SCALE TRIALS THAT USE PRECISION EQUIPMENT TO COLLECT AND ANALYZE DATA, AND OFFER SMALL PLOT RESEARCH FOR MORE COMPLEX RESEARCH PROTOCOLS. FURTHER, PACS HAVE PLOTS DESIGNED FOR ANIMAL/LIVESTOCK RESEARCH, ADOPTION OF ORGANIC FARMING PRACTICES, AND WOODLANDS AND PONDS. THE BREADTH OF HATCH PROJECTS LEADS TO A RANGE OF DELIVERABLES AND OUTPUTS INCLUDING: DEVELOPMENT OF NEW KNOWLEDGE AND TECHNOLOGIES, ENHANCED MANAGEMENT SYSTEMS, AND BEST PRACTICES AND TECHNOLOGY ADOPTION RELATED TO CLIMATE MITIGATION, FOOD SAFETY, FOOD SUSTAINABILITY, BIOFUELS SYSTEMS, ECONOMIC POLICY, HEALTHY EATING HABITS, CONSERVATION OF NATURAL RESOURCES, ETC. STAKEHOLDERS THAT DIRECTLY BENEFIT FROM PURDUE'S HATCH FUNDING ARE COMMODITY GROUPS (E.G., INDIANA SOYBEAN ALLIANCE AND INDIANA CORN GROWERS ASSOCIATION); FARMERS OF SMALL AND LARGE-SCALE AGRICULTURE, AND MILITARY VETERANS AND UNDERSERVED FARMERS; COMMUNITY RESIDENTS; AGENCIES/ORGANIZATIONS; INDUSTRY (SEED COMPANIES, ANIMAL FEED COMPANIES, HERBICIDE AND PESTICIDE COMPANIES); AND THE AGRICULTURAL RESEARCH COMMUNITY.

PURDUE'S COLLEGE OF AGRICULTURE'S 2021-2026 STRATEGIC PLAN OUTLINES THE VISION AND MISSION: TO EMBODY THE IDEAL OF A CONTEMPORARY LAND-GRANT MISSION TO PREPARE TOMORROW'S LEADERS FOR MEETING SOCIETY'S NEEDS, AND TO ACHIEVE WORLDWIDE LEADERSHIP IN GROWING A SUSTAINABLE FUTURE BY ADDRESSING CHALLENGES IN FOOD, LIFE AND NATURAL RESOURCE SCIENCES, WORKING ACROSS DISCIPLINES. HATCH FUNDING FROM THE USDA NATIONAL INSTITUTE FOR FOOD AND AGRICULTURE (NIFA) ENABLES PURDUE'S COLLEGE OF AGRICULTURE (COA) TO ACCOMPLISH ITS STRATEGIC PLAN THROUGH A BROAD PORTFOLIO OF RESEARCH ACROSS THREE UNITS ON THE WEST LAFAYETTE CAMPUS. PURDUE FACULTY IN THE COA, COLLEGE OF VETERINARY MEDICINE, AND SELECTED DEPARTMENTS IN THE COLLEGE OF HEALTH AND HUMAN SCIENCES WHO HAVE RESEARCH APPOINTMENTS FUNDED AT 20% OR MORE BY FORMULA FUNDS ARE REQUIRED TO SUBMIT A FIVE-YEAR PLAN OF RESEARCH. THESE HATCH PROJECTS INCLUDE BOTH FIELD- AND LABORATORY-BASED RESEARCH (FUNDAMENTAL AND APPLIED) THAT DIRECTLY CONNECT WITH CRITICAL ISSUES CREATED TO INCORPORATE COA INITIATIVES, AND TO ALIGN WITH PRIORITIES OF NIFA, RESEARCH, EDUCATION <(>&<)> ECONOMIC GOALS OF USDA, AGRICULTURE <(>&<)> FOOD RESEARCH INITIATIVE, FOUNDATION FOR FOOD <(>&<)> AGRICULTURE RESEARCH, AND EXTENSION COMMITTEE ON ORGANIZATION <(>&<)> POLICY. CRITICAL ISSUES ARE CLIMATE CHANGE, NATURAL RESOURCES AND THE ENVIRONMENT, AND SUSTAINABLE ENERGY; WORKFORCE DEVELOPMENT; POSITIVE YOUTH DEVELOPMENT AND 4-H OPPORTUNITIES; BIG DATA, INTERNET OF THINGS, BROADBAND ACCESS, DIGITAL LITERACY, INCLUSION, AND INNOVATION; HUMAN, FAMILY, AND COMMUNITY HEALTH; FOOD PRODUCTION, SECURITY, AND SAFETY; AND URBAN AGRICULTURE AND URBAN EXTENSION. THE PORTFOLIO OF PROJECTS INCLUDES ECONOMIC RESEARCH, PLANT AND ANIMAL GENETIC AND BREEDING, SUSTAINABLE AGRICULTURAL PRACTICES INCLUDING COVER CROPS AND OTHER MANAGEMENT PRACTICES TO REDUCE FARM INPUTS WHILE INCREASING PRODUCTIVITY, MOLECULAR BIOCHEMICAL APPROACHES TO UNDERSTAND PLANT TRAITS AND HUMAN NUTRITION, SOCIAL SCIENCE OF RURAL AND MIGRANT COMMUNITIES, AND TECHNOLOGICAL ADVANCES TO QUICKLY DETECT THE PRESENCE OF PATHOGENS IN PRODUCE, TO NAME A FEW. PURDUE'S AGRICULTURAL CENTERS (PACS) AND AGRONOMY CENTER FOR RESEARCH AND EDUCATION (ACRE) ARE VALUABLE RESOURCES FOR AGRICULTURAL RESEARCHERS FROM VARIOUS DISCIPLINES THE PACS ARE LOCATED STRATEGICALLY ACROSS INDIANA, THESE CENTERS OFFER DIVERSE LAND AND SOIL TYPES, AND MICROCLIMATES, ALLOWING SCIENTISTS TO CONDUCT RESEARCH IN REAL-WORLD CONDITIONS. ACRE IS LOCATED NEAR THE MAIN CAMPUS. BOTH THE PACS AND ACRE OFFER UNIQUE ADVANTAGES TO SCIENTISTS WITH LARGE PLOT RESEARCH FOR FIELD-SCALE TRIALS THAT USE PRECISION EQUIPMENT TO COLLECT AND ANALYZE DATA, AND OFFER SMALL PLOT RESEARCH FOR MORE COMPLEX RESEARCH PROTOCOLS. FURTHER, PACS HAVE PLOTS DESIGNED FOR ANIMAL/LIVESTOCK RESEARCH, ADOPTION OF ORGANIC FARMING PRACTICES, AND WOODLANDS AND PONDS. THE BREADTH OF HATCH PROJECTS LEADS TO A RANGE OF DELIVERABLES AND OUTPUTS INCLUDING: DEVELOPMENT OF NEW KNOWLEDGE AND TECHNOLOGIES, ENHANCED MANAGEMENT SYSTEMS, AND BEST PRACTICES AND TECHNOLOGY ADOPTION RELATED TO CLIMATE MITIGATION, FOOD SAFETY, FOOD SUSTAINABILITY, BIOFUELS SYSTEMS, ECONOMIC POLICY, HEALTHY EATING HABITS, CONSERVATION OF NATURAL RESOURCES, ETC. STAKEHOLDERS THAT DIRECTLY BENEFIT FROM PURDUE'S HATCH FUNDING ARE COMMODITY GROUPS (E.G., INDIANA SOYBEAN ALLIANCE AND INDIANA CORN GROWERS ASSOCIATION); FARMERS OF SMALL AND LARGE-SCALE AGRICULTURE, AND MILITARY VETERANS AND UNDERSERVED FARMERS; COMMUNITY RESIDENTS; AGENCIES/ORGANIZATIONS; INDUSTRY (SEED COMPANIES, ANIMAL FEED COMPANIES, HERBICIDE AND PESTICIDE COMPANIES); AND THE AGRICULTURAL RESEARCH COMMUNITY.

THE PURDUE UNIVERSITY COLLEGE OF AGRICULTURE'S 2021-2026 STRATEGIC PLAN OUTLINES A VISION AND MISSION THAT EMBODIES A CONTEMPORARY LAND-GRANT APPROACH BY PREPARING TOMORROW'S LEADERS TO MEET SOCIETY'S NEEDS. WE STRIVE TO LEAD GLOBALLY BY CULTIVATING INNOVATION AND SOLUTIONS THAT WILL SHAPE AMERICA'S FUTURE IN THE VITAL AREAS OF FOOD, LIFE, AND NATURAL RESOURCE SCIENCES. EFFORTS ARE ALREADY UNDERWAY TO DEVELOP THE NEXT ITERATION OF THE STRATEGIC PLAN, BUILDING ON THESE GUIDING PRINCIPLES AND ACCOMPLISHMENTS. HATCH FUNDING FROM THE USDA NATIONAL INSTITUTE FOR FOOD AND AGRICULTURE (NIFA) ENABLES PURDUE'S COLLEGE OF AGRICULTURE (COA) TO ACCOMPLISH ITS STRATEGIC PLAN THROUGH A BROAD PORTFOLIO OF RESEARCH ACROSS THREE UNITS ON THE WEST LAFAYETTE CAMPUS. SUPPORT FROM HATCH FUNDING, PROVIDED BY THE USDA NATIONAL INSTITUTE FOR FOOD AND AGRICULTURE (NIFA), PLAYS A VITAL ROLE IN ENABLING THE COLLEGE OF AGRICULTURE TO FULFILL ITS STRATEGIC OBJECTIVES. THIS FUNDING SUPPORTS A DIVERSE PORTFOLIO OF RESEARCH CONDUCTED ACROSS THREE ACADEMIC UNITS ON PURDUE'S WEST LAFAYETTE CAMPUS. FACULTY MEMBERS IN THE COLLEGE OF AGRICULTURE, THE COLLEGE OF VETERINARY MEDICINE, AND SELECTED DEPARTMENTS WITHIN THE COLLEGE OF HEALTH AND HUMAN SCIENCES-WHO RECEIVE 20% OR MORE OF THEIR RESEARCH FUNDING THROUGH FORMULA FUNDS-ARE REQUIRED TO SUBMIT A FIVE-YEAR RESEARCH PLAN ALIGNED WITH THE STRATEGIC PRIORITIES. THESE HATCH PROJECTS, WHICH ARE THEN REVIEWED, INCLUDE BOTH FIELD- AND LABORATORY-BASED RESEARCH (APPLIED AND FUNDAMENTAL) THAT DIRECTLY CONNECT WITH CRITICAL ISSUES CREATED TO INCORPORATE COA INITIATIVES, AND TO ALIGN WITH PRIORITIES OF NIFA, RESEARCH, EDUCATION <(>&<)> ECONOMIC GOALS OF USDA, AGRICULTURE <(>&<)> FOOD RESEARCH INITIATIVE, FOUNDATION FOR FOOD <(>&<)> AGRICULTURE RESEARCH, AND EXTENSION COMMITTEE ON ORGANIZATION <(>&<)> POLICY. CRITICAL ISSUES ARE NATURAL RESOURCES; WORKFORCE DEVELOPMENT; POSITIVE YOUTH DEVELOPMENT AND 4-H OPPORTUNITIES; AGRICULTURAL AND DIGITAL TECHNOLOGY AND INNOVATIONS; HUMAN, FAMILY, AND COMMUNITY HEALTH; PROFITABLE FARM OPERATIONS, FOOD PRODUCTION, AGRO-SECURITY, SPECIALTY CROPS, AND SMALL-SCALE FARMING. THE PORTFOLIO OF PROJECTS INCLUDES ECONOMIC RESEARCH, PLANT AND ANIMAL GENETIC IMPROVEMENT AND BREEDING, MANAGEMENT PRACTICES TO OPTIMIZE FARMING AND PRODUCTIVITY, MOLECULAR BIOCHEMICAL APPROACHES TO UNDERSTAND AND MANAGE PLANT TRAITS AND IMPROVE HUMAN NUTRITION, SOCIAL SCIENCE OF RURAL COMMUNITIES, AND TECHNOLOGICAL ADVANCES TO QUICKLY DETECT THE PRESENCE OF PATHOGENS, TO NAME JUST A FEW. PURDUE'S AGRICULTURAL CENTERS (PACS) AND AGRONOMY CENTER FOR RESEARCH AND EDUCATION (ACRE) ARE V ALUABLE RESOURCES FOR AGRICULTURAL RESEARCHERS FROM VARIOUS DISCIPLINES. LOCATED STRATEGICALLY ACROSS INDIANA, THE PACS OFFER VARYING LAND AND SOIL TYPES AND MICROCLIMATES, ALLOWING SCIENTISTS TO CONDUCT RESEARCH IN REAL-WORLD CONDITIONS. ACRE IS LOCATED NEAR THE MAIN CAMPUS. BOTH THE PACS AND ACRE OFFER UNIQUE ADVANTAGES TO SCIENTISTS: THE PACS PROVIDE LARGE PLOT RESEARCH FOR FIELD-SCALE TRIALS USING PRECISION EQUIPMENT TO COLLECT AND ANALYZE DATA, WHILE ACRE OFFERS SMALL PLOT RESEARCH FOR MORE COMPLEX PROTOCOLS. FURTHER, THE PACS HAVE PLOTS DESIGNED FOR ANIMAL/LIVESTOCK RESEARCH, ADOPTION OF ORGANIC FARMING PRACTICES, AND WOODLANDS AND PONDS. THE BREADTH OF HATCH PROJECTS LEADS TO A RANGE OF DELIVERABLES AND OUTPUTS, INCLUDING THE DEVELOPMENT OF NEW KNOWLEDGE AND TECHNOLOGIES, ENHANCED MANAGEMENT SYSTEMS, AND BEST PRACTICES AND TECHNOLOGY ADOPTION. THESE EFFORTS AIM TO INCREASE AGRICULTURAL PRODUCTION AND PROFITABILITY, IMPROVE FOOD SAFETY, INFLUENCE ECONOMIC POLICY, PROMOTE HEALTHY EATING HABITS, AND CONSERVE NATURAL RESOURCES. STAKEHOLDERS THAT DIRECTLY BENEFIT FROM PURDUE'S HATCH FUNDING ARE COMMODITY GROUPS; FARMERS OF SMALL AND LARGE-SCALE AGRICULTURE, AND VETERANS; COMMUNITY RESIDENTS; AGENCIES/ORGANIZATIONS; INDUSTRY (SEED COMPANIES, ANIMAL FEED COMPANIES, HERBICIDE AND PESTICIDE COMPANIES); AND THE RESEARCH COMMUNITY.

OMNIBUS ABSTRACT THE GREAT LAKES REGION FACES MANY CHALLENGESCLIMATE CHANGE IS UPON US, AS WELL AS A HOST OF OTHER CONCERNS, SUCH AS AQUATIC INVASIVE SPECIES, WATERS CONTAMINATED WITH MICROPLASTICS AND OTHER EMERGING SUBSTANCES, AND LOSS OF NATURAL HABITAT LEADING TO MORE FLOODING. ILLINOIS-INDIANA SEA GRANT (IISG), WITH ITS UNIQUE MANDATE TO BRING THE LATEST SCIENCE TO THOSE WHO CAN BEST USE THE INFORMATION, SERVES A CRITICAL ROLE IN EMPOWERING PEOPLE TO SOLVE PROBLEMS IN SUSTAINABLE WAYS. ONE OF 34 SEA GRANT PROGRAMS, IISG IS FOCUSED ON THE SOUTHERN LAKE MICHIGAN REGION104 MILES OF HEAVILY URBANIZED AND INDUSTRIALIZED SHORELINE IN ILLINOIS AND INDIANA. IN THIS OMNIBUS, IISG GOALS ARE TO IMPROVE ENVIRONMENTAL LITERACY, FOSTER A DIVERSE, SKILLED, AND ENVIRONMENTALLY LITERATE WORKFORCE, PROTECT COASTAL AND GREAT LAKES HABITATS AND ECOSYSTEMS THROUGH SCIENCE, TOOLS AND SERVICES, SUPPORT THE AQUACULTURE INDUSTRY AND RECREATIONAL FISHING COMMUNITIES, AND HELP COMMUNITIES PLAN FOR SUSTAINABLE WATER RESOURCES AND TO BE READY FOR HAZARDS DUE TO WEATHER, CLIMATE, AND OTHER THREATS. TO ACCOMPLISH ITS GOALS, IISG FUNDS AND ENGAGES IN RESEARCH TO INFORM RESOURCE MANAGEMENT, POLICY, COMMUNITY DECISION MAKING, AND PERSONAL CHOICE. IN THIS OMNIBUS, WE ARE SUPPORTING SUBRECIPIENTS THAT WILL SEEK TO BETTER UNDERSTAND GREAT LAKES CONTAMINANTS AND POLLUTION MITIGATION EFFORTS, THE ROLE OF GROUNDWATER IN LOCAL WATER SUPPLIES, AND HOW TO STABILIZE LAKE MICHIGAN SHORELINES. OVER THE COURSE OF THE OMNIBUS PERIOD, IISG WILL ALSO CONTINUE TO SUPPORT THE ANNUAL COMPETITIVE GRADUATE STUDENT SCHOLARS PROGRAM AS WELL AS OTHER COMPETITIVE RESEARCH PROJECTS. IISG ALSO CONDUCTS OUTREACH AND EDUCATION TO HELP BRING INFORMATION TO THOSE WHO CAN USE ITWE BRING DATA TO DECISION MAKERS WHETHER THATS COMMUNITIES, RESIDENTS, OR OTHER RELEVANT AUDIENCES. TO BE AS EFFECTIVE AS POSSIBLE, WE ENGAGE IN NEEDS ASSESSMENTS AND COLLABORATE WITH A VARIETY OF PARTNERS, BRINGING EVERYONE TO THE TABLE FOR INPUT, INCLUDING THOSE WHO ARE OFTEN LEFT OUT, AND SHARING OF RESOURCES AND CONNECTIONS. IISG TRAINS AND EDUCATES THOSE WHO CAN REACH MORE AUDIENCES, INCLUDING EXTENSION EDUCATORS, MASTER GARDENERS, LOCAL OFFICIALS, TEACHERS, AND NATURAL RESOURCE PROFESSIONALS, TO NAME A FEW. WE DEVELOP AND DISTRIBUTE TOOLS AND OTHER TECHNICAL, OUTREACH, AND EDUCATION PRODUCTS, HOLD WORKSHOPS AND MEETINGS, AND CONNECT WITH TARGET AUDIENCE MEMBERS ONE-ON-ONE. THE OUTCOMES OF IISGS WORK CAN BROADLY BE SUMMED UP THAT MORE PEOPLEESPECIALLY STRATEGICALLY RELEVANT GROUPSARE ABLE TO MAKE INFORMED CHOICES ABOUT SUSTAINABLE USE AND MANAGEMENT OF WATER RESOURCES. IN THIS OMNIBUS, OUR EFFORTS WILL HELP FOSTER RESILIENT COMMUNITIES THAT ENGAGE IN CLIMATE CHANGE ADAPTATION, IMPROVED STORMWATER MANAGEMENT, SHORELINE PROTECTION, AND SUSTAINABLE USE OF NATURAL RESOURCES. NOT JUST FISHERS, BUT EVERYONE IN THE TWO STATES WILL BENEFIT FROM OUR WORK TO PROMOTE THE HEALTH OF AQUATIC ECOSYSTEMS AS WE LEARN MORE ABOUT CONTAMINANTS, INVASIVE SPECIES, AND OTHER WATER QUALITY AND FOOD WEB THREATS, AND WE KEEP NATURAL RESOURCE MANAGERS INFORMED ON WAYS TO ADDRESS THESE ISSUES. IISGS SUPPORT OF THE AQUACULTURE INDUSTRY IN THE TWO STATES HELPS PROMOTE HEALTHY EATING AS IT BOOSTS LOCAL BUSINESSES. AND FINALLY, OUR WORK WITH K-12 TEACHERS AND STUDENTS, AS WELL AS WITH A RANGE OF COLLEGE STUDENTS, LEADS THEM TO KNOWLEDGE, EXPERIENCE, AND OPPORTUNITY. THEY DIRECTLY ENGAGE IN SCIENCE, LEARN MORE ABOUT CRITICAL LAKE MICHIGAN ISSUES, CONNECT TO POTENTIAL ROLE MODELS, AND GAIN CAREER ENHANCING EXPERIENCES. IN OTHER WORDS, WE HELP FOSTER THE NEXT GENERATION OF SCIENTISTS.

PURDUE UNIVERSITY - GEAR UP STATE GRANT - INDIANA

(CFIRE) CHARACTERIZING HIGHWAYS & AUTOMATED NAVIGATION IN CISLUNAR ENVIRONMENT (CHANCE)

EXECUTE A BALANCED SCIENCE PROGRAM BASED ON DISCIPLINE-SPECIFIC GUIDANCE FROM THE NATIONAL ACADEMIES OF SCIENCES ENGINEERING AND MEDICINE ADMINISTRATION PRIORITIES AND DIRECTION FROM CONGRESS. PARTICIPATE AS A KEY PARTNER AND ENABLER IN THE AGENCY S EXPLORATION INITIATIVE FOCUSING ON SCIENTIFIC RESEARCH OF ON AND FROM THE MOON LUNAR ORBIT MARS AND BEYOND. ADVANCE DISCOVERY IN EMERGING FIELDS BY IDENTIFYING AND EXPLOITING CROSS-DISCIPLINARY OPPORTUNITIES BETWEEN TRADITIONAL SCIENCE DISCIPLINES DEVELOP A DIRECTORATE-WIDE TARGET-USER FOCUSED APPROACH TO APPLIED PROGRAMS INCLUDING EARTH SCIENCE APPLICATIONS SPACE WEATHER PLANETARY DEFENSE AND SPACE SITUATIONAL AWARENESS.

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) -THE NATIONAL SCIENCE FOUNDATION (NSF) GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) IS A HIGHLY COMPETITIVE, FEDERAL FELLOWSHIP PROGRAM. GRFP HELPS ENSURE THE VITALITY AND DIVERSITY OF THE SCIENTIFIC AND ENGINEERING WORKFORCE OF THE UNITED STATES. THE PROGRAM RECOGNIZES AND SUPPORTS OUTSTANDING GRADUATE STUDENTS WHO ARE PURSUING RESEARCH-BASED MASTER'S AND DOCTORAL DEGREES IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) AND IN STEM EDUCATION. THE GRFP PROVIDES THREE YEARS OF FINANCIAL SUPPORT FOR THE GRADUATE EDUCATION OF INDIVIDUALS WHO HAVE DEMONSTRATED THEIR POTENTIAL FOR SIGNIFICANT RESEARCH ACHIEVEMENTS IN STEM AND STEM EDUCATION. THIS AWARD SUPPORTS THE NSF GRADUATE FELLOWS PURSUING GRADUATE EDUCATION AT THIS GRFP INSTITUTION. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

HIGH THROUGHPUT INFRASTRUCTURE FOR REACTION SCREENING AND BIOASSAYS - HIGH THROUGHPUT INFRASTRUCTURE FOR REACTION SCREENING AND BIOASSAYS MASS SPECTROMETRY (MS) IS A POWERFUL AND WIDELY APPLICABLE ANALYTICAL METHOD FOR QUALITATIVE AND QUANTITATIVE ANALYSIS OF COMPOUNDS OF ALL TYPES AND SIZES. DESORPTION ELECTROSPRAY IONIZATION (DESI) IS AN AMBIENT IONIZATION METHOD IN WHICH SAMPLES ARE ANALYZED IN THE OPEN AIR BY IMPACT OF PRIMARY DROPLETS. GIVEN THE ABILITY TO POSITION AN ARRAY OF SAMPLES RELATIVE TO THE MASS SPECTROMETER, DESI-MS BECOMES A HIGH THROUGHPUT (HT) CHEMICAL ANALYSIS METHOD. THE POWER OF MS AS AN ANALYTICAL TECHNIQUE IS WELL KNOWN BUT IT IS LESS COMMONLY REALIZED THAT MS CAN ALSO SERVE AS A PREPARATIVE METHOD, E.G. IT CAN BE USED TO DEPOSIT MASS-SELECTED IONS ON SURFACES TO CREATE NEW MATERIALS IN VACUO. OF SIGNIFICANT INTEREST TO ORGANIC SYNTHESIS, A UNIQUE FEATURE OF DESI IS THAT, UPON IMPACT, THE SPRAY OF SOLVENT USED TO ANALYZE A REACTION MIXTURE GENERATES SECONDARY MICRODROPLETS IN WHICH REACTIONS MAY BE ACCELERATED EN ROUTE TO THE MASS SPECTROMETER. IT IS THIS REMARKABLE FEATURE THAT MAKES DESI- MS A POWERFUL SYNTHETIC METHOD COMBINED WITH A BUILT-IN ANALYTICAL CAPABILITY. WITH SUPPORT OF DARPA, WE BUILT A HIGH THROUGHPUT SYSTEM AT PURDUE CAPABLE OF AUTOMATED REACTION SCREENING AT A RATE GREATER THAN 1 REACTION MIXTURE PER SECOND. WE NOW PROPOSE AN INTRAMURAL - EXTRAMURAL COLLABORATION BETWEEN PURDUE AND THE NCATS ASPIRE LABORATORY. THE UG3 COMPONENT OF THE COLLABORATION WILL FOCUS ON DESIGNING, FABRICATING, AND TESTING AN IMPROVED HIGH THROUGHPUT SYSTEM FOR REACTION SCREENING BASED ON DESI-MS. THE SYSTEM WILL REPLICATE THE CAPABILITIES OF THE EXISTING PURDUE SYSTEM AND ALSO INCLUDE NEW CAPABILITIES FOR SMALL-SCALE SYNTHESIS COMBINED WITH HIGH THROUGHPUT BIOASSAYS. IN THE UH3 PHASE OF THE PROPOSED STUDY, THE SYSTEM WILL BE TRANSFERRED TO NCATS AND USED IN COLLABORATION WITH THE INTRAMURAL GROUP. AS AN INITIAL DEMONSTRATION OF THE NEW HIGH THROUGHPUT PLATFORM CAPABILITIES, WE WILL PURSUE THE DISCOVERY OF NOVEL THERAPEUTICS FOR ADVANCED-STAGE PROSTATE CANCER, FOR WHICH CURRENT CHEMOTHERAPEUTIC AGENTS SHOW LIMITED EFFECTIVENESS. SPECIFICALLY, THIS EFFORT WILL ENTAIL LARGE-SCALE SCREENING AND SYNTHESIS OF POTENTIAL CHOLESTEROL SULFOTRANSFERASE (SULT2B1B, A CURRENTLY UNDRUGGED BIOLOGICAL TARGET) INHIBITORY COMPOUNDS, TOGETHER WITH LATE-STAGE FUNCTIONALIZATION OF BIOACTIVE SCAFFOLDS TO GENERATE A DIVERSE RANGE OF ANALOGS. THROUGH THIS EFFORT, THE SYSTEM WILL BE ESTABLISHED AS AN ALL-IN-ONE NEXT-GENERATION DRUG DISCOVERY PLATFORM, WITH INTEGRATED SCREENING, SYNTHESIS, AND BIOLOGICAL ASSAY CAPABILITIES. DURING THE LATTER STAGES OF THE UH3 PHASE, THE VERSATILITY OF THE SYSTEM WILL BE TESTED IN SEVERAL OTHER BIOLOGICAL APPLICATIONS, INCLUDING DIRECTED EVOLUTION AND FUNCTIONALIZATION OF ACETYLCHOLINESTERASE REACTIVATORS. SUCCESSFUL COMPLETION OF THESE TASKS WILL DEMONSTRATE THE NEWLY CONSTRUCTED HIGH THROUGHPUT DESI-MS PLATFORM TO BE AN EFFICIENT METHOD FOR THE DISCOVERY AND EXPANSION OF CHEMICAL SPACE TOWARDS CURRENTLY UNDRUGGED BIOLOGICAL TARGETS.

MODELING FUNCTIONAL GENOMICS OF SUSCEPTIBILITY TO THE PERSISTENT EFFECTS OF ENVIRONMENTAL TOXINS IN AN ELDERLY RURAL INDIANA NEURODEGENERATIVE COHORT - ALZHEIMER'S DISEASE (AD), AD-RELATED DEMENTIAS (ADRD) AND OTHER NEURODEGENERATIVE DISEASES SUCH AS PARKINSON’S DISEASE (PD) EXHIBIT PATHOGENIC GENE-ENVIRONMENT INTERACTIONS (GXE) WITH SYNERGISTIC EFFECTS OF EXPOSURE TO AN ENVIRONMENTAL CHEMICAL/PATHOGEN AND GENOTYPE. RECENT PROGRESS IN NEXT- GENERATION SEQUENCING HAS EXPEDITED THE DISCOVERY OF GENETIC RISK FACTORS ASSOCIATED WITH ALZHEIMER'S DISEASE, AD-RELATED DEMENTIAS AND PARKINSON’S DISEASE. YET, IDENTIFIED GENETIC FACTORS ONLY ACCOUNT FOR A FRACTION OF PATIENTS, AND NOT ALL PATIENTS WITH THE IDENTIFIED GENETIC RISKS DEVELOP DISEASE. THIS IS EXASPERATED FOR AD/ADRD/PD AS IT IS CONVOLUTED WITH MANY COVARIATES OVER A PERSON’S LIFETIME. TO ELUCIDATE THE CONTRIBUTION OF GXE TO DISEASE WE PROPOSE AN APPROACH BASED ON THE PRINCIPLES OF LATENT-PERSISTENT EFFECTS OF ENVIRONMENTAL NEUROTOXICANTS; AND THE DEVELOPMENTAL ORIGINS OF ADULT DISEASE HYPOTHESIS. WE SEEK TO TEST THE HYPOTHESIS THAT PERSISTENT NEUROTOXICITY IS DUE TO EXPOSURES ALTERING SELF-PERPETUATING HOMEOSTATIC PROCESSES THAT GIVE THE RESILIENCY AND PERPETUITY TO THE ADVERSE TOXICOLOGICAL PROCESSES BY EITHER GENETIC AND/OR EPIGENETIC MEANS. SPECIFICALLY, WE WILL COLLECT SAMPLES FROM SAME-SEX SIBLINGS IN NORTHERN INDIANA THAT PHENOTYPICALLY DIFFER IN AD/ADRD/PD RELEVANT COGNITIVE AND MOTOR DYSFUNCTION PHENOTYPES; REPROGRAM BLOOD CELLS INTO HUMAN INDUCED PLURIPOTENT STEM CELLS (HIPSCS); DIFFERENTIATE THEM INTO CORTICAL AND MIDBRAIN LINEAGES; AND CHARACTERIZE THEIR VULNERABILITY TO INDUCTION OF A PERSISTENT NEUROTOXIC STATE CAUSED BY NEURODEVELOPMENTAL EXPOSURES TO ENVIRONMENTAL HAZARD/TOXICANTS RELEVANT TO THIS REGION AND HISTORY. WE EXPECT TO IDENTIFY A PERSISTENT NEUROTOXIC STATE WITH A CONSERVED RESPONSE SHARED ACROSS INDIVIDUALS AT THE LEVEL OF THE GENETIC/EPIGENETIC PATHWAYS EVOKED. 'AGE-RELATED SIGNALING' NETWORKS HAVE BEEN DEFINED AS CENTRAL PATHWAYS REGULATING HEALTHY LIFESPAN AND AGING AND ARE THUS EXPECTED AS A SHARED NETWORK FEATURE CONFERRED BY GXE RISKS. OUR INNOVATIVE APPROACH WILL LEVERAGE SINGLE-CELL GENOMICS APPROACHES AND PATHWAY ANALYSIS TO IDENTIFY MECHANISMS ACTIVATED BY SUBJECT-SPECIFIC GXE TO CAUSE A PERSISTENT NEUROTOXIC STATE WITH ONLY A SMALL SUBJECT SIZE AND LOW FDR. THE FOLLOWING AIMS WILL TEST OUR HYPOTHESIS AND VALIDATE THE SHARED SIGNALING NETWORKS: AIM 1: IDENTIFY SUBJECT BY TOXICANT INTERACTIONS CONTRIBUTING TO PERSISTENT NEUROTOXICITY USING HUMAN CELLS DERIVED FROM PAIRED ALZHEIMER'S DISEASE, AD-RELATED DEMENTIAS AND PARKINSON’S DISEASE AND HEALTHY COHORT WITH COMPARABLE EXPOSURE HISTORIES; AIM 2: IDENTIFY GENETIC PATHWAYS ASSOCIATED WITH ESTABLISHING A PERSISTENT NEUROTOXIC STATE VIA SINGLE-CELL GENOMICS AND BIOINFORMATIC COMPARISONS TO POPULATION LEVEL DATA; AND AIM 3: VALIDATE THE GENETIC PATHWAYS OF GXE INDUCTION OF PERSISTENT NEUROTOXICITY WITH IN VIVO AND IN VITRO MODELS. THIS WORK SEEKS TO UNDERSTAND HOW PAST ENVIRONMENTAL EXPOSURES INFLUENCE AD/ADRD/PD DISEASE RISK AND INCIDENCE BY UTILIZING AN INTERDISCIPLINARY ACADEMIC- COMMUNITY PARTNERSHIP TO STUDY ELDERLY SUBJECTS AT RISK FOR AD/ADRD/PD. THE FINDINGS MAY ALSO IDENTIFY TARGETS OF THE GXE INTERACTIONS THAT CONTRIBUTE TO THE INCREASED RISK OF ALZHEIMER'S DISEASE, AD-RELATED DEMENTIAS AND PARKINSON’S DISEASE OVER OUR LIFETIME.

OPTNET: OPTIMIZATION WITH P-BIT NETWORKS

FRAMEWORKS: STREAMCI: AN AI-READY STREAMING DATA PLATFORM FOR A WIDE RANGE OF SCIENTIFIC APPLICATIONS -THIS PROJECT CREATES STREAMCI, AN OPEN-SOURCE STREAMING DATA PLATFORM DESIGNED TO HELP RESEARCHERS AND USERS ACROSS INDUSTRIES TO MORE EFFECTIVELY HARNESS MASSIVE SENSOR DATA STREAMS USING MODERN DATA ANALYSIS METHODS SUCH AS ARTIFICIAL INTELLIGENCE (AI) AND MACHINE LEARNING (ML). STREAMCI SIMPLIFIES THE COLLECTION, MANAGEMENT, AND ANALYSIS OF SENSOR DATA STREAMS IN A USER-FRIENDLY, CLOUD-BASED SYSTEM ACCESSIBLE TO THE BROAD RESEARCH COMMUNITY. BY LOWERING TECHNICAL BARRIERS AND MAKING DATA AI-READY, STREAMCI EMPOWERS DOMAIN EXPERTS TO BUILD INTELLIGENT AND RESPONSIVE APPLICATIONS THAT DRIVE FASTER DISCOVERIES AND MORE EFFECTIVE SOLUTIONS. THE PLATFORM ALSO SERVES AS AN OPEN EDUCATIONAL RESOURCE, TRAINING THE NEXT GENERATION OF DATA- AND AI-SAVVY RESEARCHERS TO CREATE DATA-DRIVEN SOLUTIONS FOR CRITICAL SOCIETAL NEEDS. STREAMCI IS DESIGNED TO STREAMLINE THE ENTIRE WORKFLOW FOR SENSOR DATA STREAMS, FROM CAPTURING RAW SENSOR DATA TO PROCESSING IT AT VARIOUS LEVELS OF FIDELITY, ANONYMIZATION, AND TRANSFORMATION; AND TO APPLY SUITABLE ML METHODS ACROSS DIFFERENT MODALITIES AND ENABLE FINDABLE, ACCESSIBLE, INTEROPERABLE, AND REUSABLE (FAIR) DATA SHARING FOR RESEARCH REPRODUCIBILITY AND CROSS-DOMAIN SCIENCE. THE CORE INNOVATIONS OF THE PROJECT INCLUDE HIGH-LEVEL DATA ABSTRACTIONS THAT ALLOW RESEARCHERS TO COMBINE DATA STREAMS ACROSS SOURCES; AI-READINESS THROUGH NOVEL TOOLS FOR DATA PREPARATION AND CANONICAL AND CUSTOMIZED DATA PIPELINES; LOW-CODE APPLICATION DEVELOPMENT AND INTEGRATION OF POWERFUL TOOLS; AND SCALABLE, SEAMLESS SERVICE DEPLOYMENT AND DELIVERY. STREAMCI IS USED ACROSS A WIDE RANGE OF DOMAINS, INCLUDING ENERGY, MANUFACTURING, TRANSPORTATION, AGRICULTURE, ECOLOGY, AUDIOLOGY, AND EDUCATION, DEMONSTRATING ITS BROAD APPLICABILITY AND VERSATILITY. STREAMCI IS DEPLOYED AS AN OPEN-SOURCE, CLOUD-BASED SOFTWARE-AS-A-SERVICE. ITS OPEN-SOURCE RELEASE ALLOWS RESEARCHERS TO SET UP AND OPERATE STREAMCI ON THEIR LOCAL COMPUTERS. 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 RESEARCH: RESEARCH INFRASTRUCTURE: CFS (TRACK III) COSMOGENIC NUCLIDES IN EARTH SCIENCE RESEARCH: ALLIED FACILITIES FOR SAMPLE PREPARATION, ANALYSIS, AND TRAINING -ACCELERATOR MASS SPECTROMETRY (AMS) IS A TECHNIQUE USED TO MEASURE EXCEEDINGLY RARE MATERIALS PRODUCED AS COSMIC RAYS INTERACT WITH ROCKS, SOIL, AND EARTH?S ATMOSPHERE. USING THESE DATA, SCIENTISTS CAN DETERMINE THE TIMING OF EVENTS THAT HAVE THE POTENTIAL TO IMPACT HUMAN ENDEAVORS. SOME CATASTROPHIC CHANGES, LIKE FLOODS OR EARTHQUAKES, OCCUR OVER SHORT TIME-SCALES, WHILE OTHERS, LANDSCAPE EROSION AND THE GROWTH AND DEMISE OF ICE SHEETS, OCCUR OVER LONGER TIME-SCALES, THOUSANDS TO MILLIONS OF YEARS. THESE CHANGES DIRECTLY IMPACT THE WELFARE OF HUMAN POPULATIONS WORLD-WIDE. THIS AWARD RENEWS FUNDING FOR THE PURDUE RARE ISOTOPE MEASUREMENT LABORATORY (PRIME LAB) AND THE UNIVERSITY OF VERMONT (UVM) COMMUNITY COSMOGENIC FACILITY. THESE TWO FACILITIES WILL COLLABORATE TO PRODUCE A NATIONAL, MULTI-USER FACILITY DEDICATED TO THE MEASUREMENT OF COSMOGENIC RADIONUCLIDES USING ACCELERATOR MASS SPECTROMETRY. DOING SO ALLOWS THE COMBINED FACILITY TO TRAIN STUDENTS AND RESEARCHERS FROM DOZENS OF UNIVERSITIES WITHIN THE US THAT DO NOT HAVE THESE CAPABILITIES OR THE FUNDS TO CREATE THEM. AT THE UNIVERSITY OF VERMONT, STUDENTS LEARN HOW TO PERFORM THE PHYSICAL AND CHEMICAL PREPARATION OF SAMPLES AND THEN PARTICIPATE IN THE MEASUREMENT OF THEIR SAMPLES ON THE PRIME LAB AMS. THE INTERACTION BETWEEN STUDENTS, FACULTY, AND PROFESSIONAL STAFF AT PRIME LAB AND UNIVERSITY OF VERMONT FACILITATES INTERACTION WITH GEOLOGISTS, CHEMISTS, AND PHYSICISTS, PROVIDING A UNIQUE OPPORTUNITY TO EXPAND THE EDUCATIONAL OPPORTUNITY BEYOND THE FOCUS OF SPECIFIC RESEARCH PROJECTS. AN ESSENTIAL COMPONENT OF THIS AWARD IS OUTREACH TO UNDERREPRESENTED COMMUNITIES, WHICH WILL PROVIDE STUDENTS HANDS-ON OPPORTUNITIES TO PARTICIPATE IN GEOLOGIC FIELD WORK, LABORATORY INSTRUCTION, AND EXPOSURE TO NUCLEAR PHYSICS MEASUREMENT TECHNIQUES. THE COLLABORATIVE FACILITY GOALS ARE TO PROVIDE ALLIED SAMPLE PREPARATION, CHEMICAL EXTRACTION, AND AMS MEASUREMENTS OF COSMOGENIC AND OTHER LONG-LIVED RADIONUCLIDES TO THE GEOSCIENCE COMMUNITY. THE FIRST GOAL OF THIS PROPOSAL IS THE CONTINUANCE OF THIS SAMPLE PREPARATION AND MEASUREMENT CAPABILITY FOR THE NSF AND GEOSCIENCE COMMUNITY. PRIME LAB HAS PROVIDED AMS MEASUREMENTS FOR THE GEOSCIENCE COMMUNITY SINCE THE EARLY 1990?S. PRIME LAB PROVIDES MEASUREMENTS OF 10BE, 14C, 26AL, 36CL, AND 129I IN TERRESTRIAL GEOLOGIC SAMPLES. PRIME LAB ROUTINELY MEASURES THOUSANDS OF UNKNOWNS ANNUALLY FOR RESEARCHERS, INCLUDING THOSE IN THE NSF COMMUNITY, BUT THE LABORATORY CAN NEITHER KEEP PACE WITH DEMAND AND ADEQUATELY TRAIN ENOUGH ?NEXT-GENERATION? COSMOGENIC NUCLIDES RESEARCHERS. ACCORDINGLY, A SIGNIFICANT GOAL OF THIS AWARD IS THE ESTABLISHMENT OF ADDITIONAL SAMPLE PREPARATION FACILITIES FOR THE GEOSCIENCE COMMUNITY. THE COMBINATION OF THE AMS MEASUREMENT CAPABILITIES AT PRIME LAB WITH THE SAMPLE PREPARATION FACILITIES AT UVM HAS VALUE BEYOND JUST THE COMBINATION OF TWO FACILITIES. COMBINING THE GROUPS ENABLES US TO EXPLORE TECHNIQUES THAT ALLOW THE FACILITY TO STREAMLINE SOME OF THE PROCESSES, IDENTIFY POTENTIAL PROBLEMS IN THE APPLICATION OF COSMOGENIC NUCLIDES, ALLOW FOR UNIQUE OPPORTUNITIES TO TRAIN THE NEXT GENERATION OF COSMOGENIC NUCLIDE RESEARCHERS, AND DEVELOP NEXT-GENERATION MEASUREMENT TECHNIQUES AND APPLICATIONS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

COLLABORATIVE RESEARCH: SCIPE: CYBERINFRASTRUCTURE PROFESSIONALS INNOVATING AND BROADENING THE ADOPTION OF ADVANCED TECHNOLOGIES (CI PIVOT) -SCIENCE AND ENGINEERING RESEARCH AND EDUCATION HAVE DYNAMIC AND GROWING NEEDS ENCOMPASSING NEW TECHNOLOGY REQUIREMENTS FROM PHYSICS-BASED SIMULATION TO ARTIFICIAL INTELLIGENCE AND USING COMPUTING THROUGH WORKFLOWS SPANNING LOCAL COMPUTING RESOURCES TO THE PUBLIC CLOUD. THE NUMBER OF CYBERINFRASTRUCTURE (CI) PROFESSIONALS CRITICAL TO SUPPORT THESE ACTIVITIES WITHIN THE RESEARCH ENTERPRISE AT HIGHER EDUCATION INSTITUTIONS IS TOO FEW AND, FREQUENTLY, NOT WELL-INTEGRATED INTO REGIONAL AND NATIONAL EFFORTS THAT WOULD SERVE AS SOURCES OF INNOVATION. THIS PROJECT, CI PIVOT, WILL ADDRESS THESE WORKFORCE ISSUES BY CREATING SEVERAL TEAMS OF CI PROFESSIONALS TRAINED WITH TAILORED, BEST-OF-BREED EDUCATIONAL MATERIALS WHO WILL CONTRIBUTE, COLLABORATE, AND CO-CREATE AS PART OF LOCAL, REGIONAL, AND NATIONAL RESEARCH PARTNERSHIPS. THESE PARTNERSHIPS WILL PROMOTE THE PROGRESS OF SCIENCE AND RESULT IN SIGNIFICANT ADVANCES IN THE FIELDS OF GEOSCIENCE, ENGINEERING, AND SOCIAL BEHAVIORAL AND ECONOMIC SCIENCES. CI PIVOT WILL FURTHER CONTRIBUTE TO THE NATIONAL INTEREST OF DEVELOPING A GLOBALLY-COMPETITIVE, DIVERSE WORKFORCE AND BROADENING PARTICIPATION THROUGH INNOVATIVE PROJECT ACTIVITIES. THE TEAM'S GOALS INCLUDE: 1) ENABLING CROSS-INSTITUTIONAL PARTNERSHIPS, SUSTAINABILITY, AND PROMOTION OF CIPS AS VALUABLE AND VALUED RESEARCH PARTNERS; 2) SUPPORTING AND ADVANCING NATIONAL RESEARCH PROJECTS; 3) BUILDING A SCALABLE WORKFORCE DEVELOPMENT IN GEOSCIENCE, ENGINEERING, AND SOCIAL BEHAVIORAL AND ECONOMIC SCIENCES FOR THE ADVANCEMENT OF TRUSTWORTHY COMPUTATIONAL SCIENCE; AND 4) LOWERING THE BARRIER TO ENTRY FOR BUILDING INSTITUTIONAL RESEARCH (SUPPORT) CAPACITY FOR INSTITUTIONS BEYOND OUR OWN. TO ACTUALIZE THESE GOALS, CI PIVOT WILL EMPLOY PROGRAMMATIC ACTIVITIES PRIORITIZING INCLUSIVENESS AND BROADENING REPRESENTATION. THESE ACTIVITIES CONSIST OF LISTENING TOURS (STAKEHOLDER INTERVIEWS AND REQUIREMENTS GATHERING), CO-ENVISIONING RETREATS (TEAM SELF-SELECTED GOAL AND BEST PRACTICE SETTING), FUTURE-CREATING WORKSHOPS (METHOD TO STRATEGICALLY EVOLVE THE PROGRAM FOR STAKEHOLDERS AND FUTURE CI PROFESSIONALS), AND COMPUTATIONAL CARPENTRIES (WORKSHOPS PROMOTING COMPUTATIONAL SKILLS DEVELOPMENT). THE CI PIVOT PROGRAM WILL TRAIN CI PROFESSIONALS IN VARIOUS AREAS, INCLUDING TOOLS TO MANAGE WORKFLOWS USING ADVANCED CYBERINFRASTRUCTURE, PARALLEL, AND ACCELERATED CODE DEVELOPMENT, WORKFLOW PERFORMANCE ANALYSIS AND OPTIMIZATION, ADVANCED CYBERSECURITY, MACHINE AND DEEP LEARNING TECHNIQUES, AND CLOUD WORKFLOW ORCHESTRATION. THROUGH PRODUCTIVE COLLABORATIONS AND PARTNERSHIPS, CI PIVOT WILL ADVANCE SCIENCE WITH TECHNICAL PUBLICATIONS RELEVANT TO GEOSCIENCE, ENGINEERING, OR SOCIAL BEHAVIORAL AND ECONOMIC 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 PLANNED FOR THIS AWARD.

PURPOSE: THE NATIONAL SEA GRANT COLLEGE PROGRAM WAS ESTABLISHED BY THE U.S. CONGRESS IN 1966 (AMENDED IN 2008, PUBLIC LAW 110-394) TO BE A HIGHLY LEVERAGED FEDERAL AND STATE PARTNERSHIP TO HARNESS THE INTELLECTUAL CAPACITY OF THE NATION'S UNIVERSITIES AND RESEARCH INSTITUTIONS TO SOLVE PROBLEMS AND GENERATE OPPORTUNITIES IN COASTAL COMMUNITIES. FOR OVER 50 YEARS, THE NATIONAL SEA GRANT COLLEGE PROGRAM HAS SUPPORTED COASTAL AND GREAT LAKES COMMUNITIES THROUGH RESEARCH, EXTENSION AND EDUCATION. SEA GRANT'S MISSION IS TO ENHANCE THE PRACTICAL USE AND CONSERVATION OF COASTAL, MARINE AND GREAT LAKES RESOURCES IN ORDER TO CREATE A SUSTAINABLE ECONOMY AND ENVIRONMENT. THIS GRANT IS THE VEHICLE THROUGH WHICH ILLINOIS-INDIANA SEA GRANT LAYS OUT ITS PLAN TO IMPLEMENT THE GOALS LAID OUT IN IN THEIR FY2018-23 STRATEGIC PLAN, WHICH CAN BE FOUND AT: HTTPS://IISEAGRANT.ORG/WP-CONTENT/UPLOADS/2020/11/IISG-STRATEGIC-PLAN-2018-23B.PDF IN ADDITION TO REQUIRED GRANT PROGRESS REPORTING, THE RECIPIENT WI

LIQUIFIED NATURAL GAS FOR AVIATION PROPULSION

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** DEMAND FOR ORGANIC TOMATOES CONTINUES TO GROW, YET FARMERS STRUGGLE TO KEEP UP DUE TO FOLIAR DISEASES THAT CAN MOVE QUICKLY THROUGH FARM FIELDS AND DECIMATE ENTIRE CROPS. THE TOMATO ORGANIC MANAGEMENT AND IMPROVEMENT PROJECT (TOMI) HAS SPENT THE PAST 10 YEARS WORKING WITH ORGANIC FARMERS TO OVERCOME THIS CHALLENGE THROUGH BREEDING AND INVESTIGATING HOW TO PROMOTE BENEFICIAL PLANT-SOIL-MICROBIAL RELATIONSHIPS. NOW WE PROPOSE TO BUILD ON THE KNOWLEDGE AND RESOURCES WE HAVE DEVELOPED AND CREATE PRACTICAL TOOLS ORGANIC FARMERS CAN USE TO PREVENT FOLIAR DISEASE OUTBREAKS AND DELIVER TOMATOES WITH END-USE QUALITY TRAITS DEMANDED BY CONSUMERS IN LOCAL MARKETPLACES. SPECIFICALLY, WE WILL: 1) IDENTIFY CRITICAL FACTORS NEEDED TO PROMOTE THE EFFICACY OF BIOCONTROL AGENTS AND ADAPT DISEASE FORECASTING MODELS TO ACCOUNT FOR THESE PRACTICES; 2) USE NEW MOLECULAR MARKERS DEVELOPED IN OUR BREEDING PROGRAM FOR PROMOTING PLANT ASSOCIATIONS WITH MICROBES THAT HAVE BIOCONTROL CAPABILITIES AND DISEASE RESISTANCE TRAITS, ESTABLISH REGIONAL PARTICIPATORY BREEDING PROGRAMS TO SELECT NEW GERMPLASM FROM THESE POOLS, AND DEVELOP A NEW DECISION-SUPPORT TOOL THAT WILL HELP FARMERS SELECT VARIETIES BEST-ADAPTED TO THEIR FARMS; 3) CREATE NEW SUPPORT NETWORKS THAT WILL HELP ORGANIC FARMERS, EXTENSION EDUCATORS, RESEARCHERS, STUDENTS AND LOCAL FOOD SYSTEM ACTORS (IE. CHEFS) CONNECT, OVERCOME PRODUCTION CHALLENGES THROUGH PARTICIPATORY RESEARCH, AND FOSTER NEW MARKETING RELATIONSHIPS; AND 4) DELIVER NOVEL AND INCLUSIVE EDUCATIONAL PROGRAMS THAT SUPPORT THESE EFFORTS. THESE PROGRAMS WILL BE DISSEMINATED BROADLY THROUGH OUR WEBSITE HOSTED BY EORGANIC, IN WEBINARS, ON-FARM WORKSHOPS, PRINT-BASED MATERIALS, VARIETY SHOWCASES AND TOMATOFESTS. RESULTS WILL BE APPLICABLE TO OTHER CROPS.

FRAMEWORKS: CYBERINFRASTRUCTURE FOR URBAN TREE RESILIENCE AND ENVIRONMENTAL EQUITY (UTREE) -WITH 89% OF THE U.S. POPULATION AND 68% OF THE WORLD POPULATION PROJECTED TO LIVE IN CITIES BY 2050, RISING URBANIZATION WILL WORSEN ALREADY SIGNIFICANT ENVIRONMENTAL CHALLENGES SUCH AS EXCESSIVE HEAT, POOR AIR QUALITY, AND RAINWATER RUNOFF. WITH URBAN TREES RECOGNIZED FOR THEIR POTENTIAL TO AMELIORATE THESE ISSUES, MANY LARGE CITIES ARE ALLOCATING RESOURCES FOR OBTAINING THE ACCURATE UP-TO-DATE TREE INVENTORIES NECESSARY FOR MANAGING URBAN FORESTS. HOWEVER, CITIES CURRENTLY COLLECT DATA THROUGH LABOR-INTENSIVE, ONE-TIME MANUAL SURVEYS OF PUBLIC TREES OR VIA COARSE LOW ACCURACY CANOPY COVER ESTIMATION. IN ADDITION, THESE METHODS LACK ACCESS TO THE SIGNIFICANT PORTION OF TREES ON PRIVATE PROPERTY. AS A RESULT, URBAN RESEARCH AND MANAGEMENT COMMUNITIES LACK CRITICAL INFORMATION ABOUT TREE DENSITY, TREE SPECIES, LOCATIONS OF TREES ACROSS DIFFERENT LAND TYPES, AND CHANGES OF TREE COUNTS OVER TIME AND EVENTS. THIS PROJECT WILL ADDRESS TIME-CRITICAL GAPS OF DATA COMPLETENESS, ACCURACY, AND EQUITY AND OF TOOL AVAILABILITY WITH THE DEVELOPMENT OF THE FIRST-EVER CLOUD-BASED CYBERINFRASTRUCTURE (CI) SUPPORTING NATIONAL (AND POTENTIALLY WORLDWIDE) URBAN TREE INVENTORY ESTIMATION THAT IN TURN WILL IMPROVE MULTIDISCIPLINARY URBAN RESEARCH, ENGINEERING, AND PLANNING TO YIELD SAFER AND MORE LIVABLE CITIES INTO THE FUTURE. MOREOVER, SUSTAINING THE CI WILL NEED GRADUALLY LESS COMPUTATION AS THE SYSTEM BENEFITS FROM TRAINED GENERATIVE MODELING AND TRANSFER LEARNING. IN ADDITION TO BROAD DISSEMINATION TO SCIENCE AND ENGINEERING COMMUNITIES AND TO URBAN STAKEHOLDERS AND PRACTITIONERS, THE EFFORT WILL TARGET RECRUITMENT OF UNDERREPRESENTED MINORITIES THROUGH CAMPUS PROGRAMS IN ORDER TO BROADEN PARTICIPATION OF DIVERSE GRADUATE STUDENTS IN ECOLOGICAL AND COMPUTER SCIENCE-RELATED DISCIPLINES. RESEARCHERS ARMED WITH THE INCREASED COMPUTATIONAL POWER AND ADVANCEMENT OF RECENT NOVEL URBAN CANOPY PARAMETERIZATION MODELS, URBAN ECOLOGICAL MODELS AND URBAN SOCIAL SCIENCE LINKAGES ARE NOW PROVIDING DRAMATICALLY IMPROVED ABILITIES TO PERFORM COMPREHENSIVE PREDICTIONS. HOWEVER, THE LACK OF HIGH-RESOLUTION TREE DATA INTEGRATED WITH SUCH POWERFUL SIMULATION TOOLS, PARTICULARLY IN UNDER-RESOURCED COMMUNITIES, REMAINS A SIGNIFICANT BARRIER TO TRANSFORMATIVE IMPACTS OF URBAN CANOPY ESTIMATIONS AND PREDICTIONS.?THIS CI WILL USE A SPATIO-TEMPORAL GENERATIVE ARTIFICIAL INTELLIGENCE APPROACH CAPABLE OF DETERMINING HIGHLY ACCURATE LOCATIONS AND SPECIES OF URBAN TREES IN CITIES. FURTHER, THE TEAM WILL ADDRESS NON-TRIVIAL CHALLENGES IN DATA MANAGEMENT AND CI INTEROPERABILITY TO ENABLE RESEARCH WORKFLOWS THAT SEAMLESSLY INTEGRATE BIG REMOTE SENSING DATA, DESKTOP SIMULATION TOOLS, HPC-OPTIMIZED SIMULATION MODELS, AND WEB-BASED INTERACTIVE DASHBOARDS TO PROVIDE A SET OF DIVERSE TOOLS CAPABLE OF PERFORMING MITIGATION SIMULATIONS AND VISUALIZATIONS. BUILDING ON TEAM MEMBERS' PRIOR EXPERIENCE AND A PRIOR NSF ELEMENTS PROJECT, CURRENT TOOLS WILL BE EXTENDED TO AUTOMATICALLY LINK URBAN TREE-RELATED DATA TO THE COMMUNITY?S URBAN PARAMETERIZATION MODELS. THE PROJECT WILL IMPACT A BROAD COMMUNITY REPRESENTED BY COMMITTED PARTNERS OF WRF/NCAR, NATIONAL DOE URBAN INTEGRATED FIELD LABS, WUDAPT, NSF LTERS, NSF ACCELNET: GLASSNET, I-TREE, CRTI, KIB/KAB, AND ARBNET. THE UTREE CI WILL BE EXTENSIBLE, PORTABLE, AND SCALABLE TO SERVE A LARGE AND MULTI-DISCIPLINARY COMMUNITY OF 60,000 RESEARCHERS AND 500,000 URBAN PRACTITIONERS AND AT THE OUTSET WILL IMPACT AN INITIAL 3.6M URBAN CITIZENS AND 9M TREES (CHICAGO AND INDIANAPOLIS). NEXT-GENERATION URBAN COMPUTATIONAL AND ECOLOGICAL RESEARCHERS AND MANAGERS WILL GAIN CRITICAL EXPOSURE TO DATA SCIENCE CONCEPTS IN URBAN TREE RESEARCH AND COMPUTATIONAL DATA ANALYTICS AND VISUALIZATION. NEARLY ONE-THIRD OF THE EARTH'S LAND SURFACE IS COVERED BY FORESTS, WHICH HOST THE MAJORITY OF TERRESTRIAL BIODIVERSITY. ACCURATE MAPPING AND MONITORING OF FORESTS ACROSS LARGE REGIONS AND OVER TIME IS CRITICAL FOR MITIGATING CLIMATE AND NATURAL HAZARDS, MANAGING NATURAL RESOURCES AND PROTECTION OF VITAL ECOSYSTEMS. WHILE TRADITIONAL GROUND-BASED MEASUREMENTS OF PLANT SPECIES AND SIZE PROVIDE THE MOST ACCURATE DATA ON FOREST STRUCTURE AND ABOVE GROUND BIOMASS, THESE METHODS BECOME IMPRACTICAL WHEN COVERING LARGE AREAS WITH HIGH-FREQUENCY REPEAT CYCLES. AIRBORNE AND SPACE-BASED REMOTE SENSING TECHNIQUES PROVIDE A TIMELY AND COST-EFFECTIVE WAY TO ASSESS FOREST STRUCTURE AND BIOMASS ON REGIONAL TO GLOBAL SCALES. SATELLITE MISSIONS FROM NASA AND ESA HAVE SENSORS THAT GATHER DATA WITH SIGNIFICANTLY MORE FREQUENT REPEAT CYCLES COMPARED TO IN SITU MEASUREMENTS OR AERIAL SURVEYS. WHILE THESE SATELLITE MISSIONS OFFER GLOBAL COVERAGE, SOME PROVIDE ONLY SPARSE DATA ON FOREST STRUCTURE AND NEED TO BE COMBINED WITH OTHER DATA SOURCES FOR PRODUCING COMPREHENSIVE AND ACCURATE WALL-TO-WALL MAPS. THERE IS A LACK OF EFFICIENT FRAMEWORKS THAT UTILIZE MULTI-SOURCE REMOTE SENSING DATA TO PRODUCE WALL-TO-WALL FOREST STRUCTURE OR ABOVE GROUND BIOMASS AT TEMPORAL AND SPATIAL SCALES NECESSARY FOR EFFECTIVE FOREST MANAGEMENT OR USE IN HAZARD MITIGATION AND MONITORING APPLICATIONS. WITHOUT SIGNIFICANT IMPROVEMENTS TO EXISTING METHODOLOGIES AND LOOKING BEYOND TRADITIONAL DATA SOURCES, EFFICIENT AND ACCURATE MONITORING OF FOREST STRUCTURE AND ABOVE GROUND BIOMASS WILL REMAIN LIMITED. OPENFOREST4D WILL ALLOW A WIDE RANGE OF USERS TO GENERATE ON-DEMAND AND UP-TO-DATE RESEARCH-GRADE FOREST STRUCTURE AND ABOVE GROUND BIOMASS ESTIMATES ACROSS A RANGE OF TIMESCALES. THIS WILL BE ACHIEVED BY APPLYING NOVEL STATISTICAL MODELS AND ARTIFICIAL INTELLIGENCE METHODOLOGIES ON A FUSION OF MULTI-SOURCE REMOTE SENSING DATA FROM GROUND, AIRBORNE AND SPACEBORNE PLATFORMS. PROVIDING THESE CYBERINFRASTRUCTURE SERVICES THROUGH EASILY ACCESSIBLE INTERACTIVE WEB-BASED INTERFACES, ALONG WITH EDUCATIONAL RESOURCES FOCUSED ON THE UNDERLYING DOMAIN SCIENCE, WILL FACILITATE TRANSFORMATIVE RESEARCH IN FOREST SCIENCES AND ECOLOGY AND ENCOURAGE BROAD COMMUNITY PARTICIPATION. OPENFOREST4D'S WEB-BASED EDUCATIONAL RESOURCES, PUBLISHED CURRICULUM MATERIALS, AND LIVE WEBINARS WILL HELP DEVELOP A DIVERSE, GLOBALLY COMPETITIVE STEM WORKFORCE. THIS AWARD BY THE OFFICE OF ADVANCED CYBERINFRASTRUCTURE IS JOINTLY SUPPORTED BY NSF'S NATIONAL DISCOVERY CLOUD FOR CLIMATE INITIATIVE. 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.

ESTROGENIC REGULATION OF SYSTEMIC VOCAL FOLD DEHYDRATION - PROJECT SUMMARY A CENTRAL ROLE OF ESTROGEN IS REGULATING HYDRATION BALANCE IN THE BODY. DECREASES IN BODY (SYSTEMIC) HYDRATION, CAUSE SYSTEMIC VOCAL FOLD DEHYDRATION. SYSTEMIC VOCAL FOLD DEHYDRATION ALTERS THE BIOLOGY OF THE TISSUE. NEVERTHELESS, THE IMPORTANCE OF ESTROGENS IN REGULATING THESE BIOLOGICAL CHANGES OF SYSTEMIC VOCAL FOLD DEHYDRATION REMAIN UNKNOWN. WE ADDRESS THIS IMPORTANT CLINICAL AND THEORETICAL ISSUE BY INVESTIGATING THE TRANSCRIPTOME, PROTEOME, TISSUE MORPHOLOGY, AND ULTRASONIC VOCALIZATION OUTCOMES IN A STUDY DESIGN THAT CAREFULLY MANIPULATES HORMONAL STATE AND HYDRATION STATE. WE WILL ALSO EXAMINE THE EFFECTS OF ESTROGEN ON THE VASCULAR GEOMETRY AND BLOOD FLOW TO THE LARYNX FOLLOWING THE INTERACTION OF SYSTEMIC DEHYDRATION WITH ALTERED HORMONAL STATES. WE USE THE RAT ANIMAL MODEL FOR THESE STUDIES SINCE THIS MODEL ALLOWS FOR ROBUST AND RIGOROUS CONTROL OF HYDRATION AND HORMONAL LEVELS. BECAUSE ESTROGEN IS IMPORTANT IRRESPECTIVE OF BIOLOGICAL SEX, BOTH MALE AND FEMALE RATS WILL BE INCLUDED. TO EXAMINE THE EFFECTS OF HORMONAL LOSS AND REPLACEMENT, WE WILL MEASURE OUTCOMES WHEN REPRODUCTIVE ORGANS HAVE BEEN SURGICALLY REMOVED (OVARIECTOMIZED AND ORCHIECTOMIZED RATS) AND WHEN ESTROGEN REPLACEMENT WITH ESTRADIOL IS DELIVERED. SYSTEMIC DEHYDRATION WILL BE INDUCED BY A TRANSLATIONAL PARADIGM OF WATER RESTRICTION FOR 5 DAYS. ANIMALS WITH FREE ACCESS TO WATER WILL SERVE AS CONTROLS FOR DEHYDRATION. ACROSS 16 ANIMAL GROUPS, OUR FIRST GOAL IS TO QUANTIFY THE EFFECTS OF HORMONAL LOSS ON THE MOLECULAR AND HISTOLOGIC SIGNATURES OF VOCAL FOLD DEHYDRATION AND THE INFLUENCE OF ESTRADIOL REPLACEMENT ON THESE SIGNATURES. BECAUSE HORMONE RECEPTORS ARE DIFFERENTIALLY LOCATED ACROSS VOCAL FOLD MUCOSA AND MUSCLE, AND THESE TISSUE LAYERS HAVE DISTINCT CELLULAR ORGANIZATION AND BIOMECHANICAL PROPERTIES, THE VOCAL FOLD MUCOSA AND MUSCLE ARE EXAMINED SEPARATELY. OUR SECOND GOAL IS TO INVESTIGATE THE INTERACTION OF HORMONAL STATUS AND DEHYDRATION ON ULTRASONIC VOCALIZATIONS. OUR THIRD GOAL IS TO EXAMINE THE INFLUENCE OF HORMONAL STATUS AND DEHYDRATION ON VASCULAR GEOMETRY, BLOOD FLOW, AND THE PHYSIOLOGIC CONSEQUENCES OF THESE CHANGES. BY COMBINING MOLECULAR, HISTOLOGICAL, AND FUNCTIONAL STUDIES, AND MECHANISTIC INVESTIGATIONS OF HEMODYNAMIC MODIFICATIONS, THIS COMPREHENSIVE PROPOSAL SEEKS TO SHED FUNDAMENTAL INSIGHT INTO THE EFFECTS OF ESTROGENS ON VOCAL FOLD DEHYDRATION BIOLOGY. THESE DATA ARE NEEDED TO DRIVE CLINICAL RECOMMENDATIONS PERTAINING TO VOCAL FOLD PHYSIOLOGY UNDER CONDITIONS OF ALTERED HYDRATION AND HORMONAL STATES.

ELUCIDATION OF ASSEMBLY AND BUDDING MECHANISMS OF SARS-COV-2 - PROJECT SUMMARY SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) IS A NOVEL CORONAVIRUS RESPONSIBLE FOR THE ONGOING HUMAN PANDEMIC (COVID-19) THAT HAS BEEN CLASSED AS A PUBLIC HEALTH EMERGENCY OF INTERNATIONAL CONCERN BY THE WORLD HEALTH ORGANIZATION (WHO). THERE IS AN URGENT DEMAND FOR SARS-COV-2 RESEARCH TO FACILITATE THE DEVELOPMENT OF THERAPEUTICS, UNDERSTAND VIRAL REPLICATION AND PATHOGENESIS, AND DETERMINE HOW THE VIRUS SPREADS FROM CELL-TO-CELL AS WELL AS PATIENT TO PATIENT. CORONAVIRUSES SUCH AS SARS AND MERS ARE AMONG THE MOST DANGEROUS PATHOGENS ON EARTH, WITH HIGH FATALITY RATES AND LACK OF VIABLE THERAPEUTICS OR VACCINES. THEY ARE CLASSIFIED AS CATEGORY C PATHOGENS BY THE NIH DUE TO THEIR EASE OF PRODUCTION AND DISSEMINATION WITH THE POTENTIAL OF HIGH MORBIDITY AND MORTALITY. DETAILED MECHANISTIC STUDIES ON THE DYNAMICS OF SARS-COV-2 REPLICATION AND VIRAL SHEDDING (I.E., BUDDING) MAY INFORM IDENTIFICATION OF NEW DRUG TARGETS IN THE VIRAL LIFE CYCLE AND ENRICH OUR UNDERSTANDING OF HOW THIS ZOONOTIC PATHOGEN UTILIZES HOST CELL LIPIDS TO BUILD THE VIRAL LIPID ENVELOPE. THE STAHELIN AND VOTH LABORATORIES, BUILDING ON COLLABORATIONS WITH EACH OTHER AND SPECIFIC EXPERTISE IN BIOCHEMISTRY, BIOPHYSICS AND COMPUTATIONAL STUDIES OF VIRUS ASSEMBLY, WILL USE EXPERIMENTAL IN VITRO AND CELLULAR STUDIES INTEGRATED WITH COMPUTATIONAL ANALYSIS TO INVESTIGATE THE CENTRAL HYPOTHESIS IN THIS GRANT: THAT SELECTIVE LIPID-PROTEIN INTERACTIONS DRIVE THE ASSEMBLY AND BUDDING OF THE M (MEMBRANE) AND N (NUCLEOPROTEIN) OF SARS- COV-2. IN TWO SPECIFIC AIMS, WE WILL (I) DETERMINE THE CELLULAR AND BIOPHYSICAL MECHANISMS BY WHICH SARS-COV- 2 M FORM VIRUS PARTICLES IN SILICO, IN VITRO AND IN HUMAN CELLS AND (II) DETERMINE HOW N LIPID BINDING DRIVES LOCALIZATION THAT CONTRIBUTES TO FORMATION OF NEW VIRAL PARTICLES. THESE STUDIES WILL BE INTEGRATED WITH STRUCTURAL BIOLOGY OF M (BROWHAN LABORATORY) AND N (OLLMANN SAPHIRE LABORATORY) AND ALSO BE VALIDATED WITH AUTHENTIC SARS-COV-2 IN A BSL-3 FACILITY IN COLLABORATION WITH THE KUHN LABORATORY. THESE QUESTIONS WILL BE STUDIED IN A TIGHTLY INTEGRATED APPROACH USING STRUCTURAL AND IN VITRO QUANTITATIVE TECHNIQUES TO ASSESS LIPID-PROTEIN AND PROTEIN-PROTEIN INTERACTIONS AND CELLULAR ASSAYS TO TEASE APART THE MOLECULAR UNDERPINNINGS OF VIRAL PROTEIN INTERACTIONS NECESSARY FOR VIRAL BUDDING AND INFECTION. COMPUTATIONALLY, WE WILL USE COARSE-GRAINED (CG) MOLECULAR DYNAMICS (MD) SIMULATIONS TO CHARACTERIZE THE ASSEMBLY PROCESS ON THE MEMBRANE AND TO IDENTIFY A SET OF MODELS FOR FURTHER REFINEMENT THROUGH ALL-ATOM (AA) MD SIMULATIONS. THIS INNOVATIVE AND INTEGRATED APPROACH WILL NOT ONLY PROVIDE CAREFUL VALIDATION OF THE RESULTS, BUT ALSO PROVIDE DETAILED STRUCTURAL INSIGHTS INTO THE LIPID-PROTEIN AND PROTEIN-PROTEIN INTERACTIONS GOVERNING THE ASSEMBLY AND BUDDING OF SARS-COV-2. THE PROTEIN INTERFACES OF M AND N IDENTIFIED IN THESE STUDIES, WHICH WILL BE KEY FOR VIRUS ASSEMBLY AND SPREAD, WILL INFORM FUTURE DRUG TARGETING AGAINST SARS-COV-2 AND OTHER CORONAVIRUSES.

DEVELOPMENT OF NOVEL ANTI-NEISSERIA GONORRHOEAE THERAPEUTIC AGENTS - PROJECT ABSTRACT: GONORRHEA IS A SEXUALLY TRANSMITTED DISEASE CAUSED BY THE BACTERIAL PATHOGEN NEISSERIA GONORRHOEAE THAT COLONIZES UROGENITAL, ANAL, AND NASOPHARYNGEAL TISSUES. LOCALLY IN THE UNITED STATES THE CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC) REPORTED A 67% INCREASE OF GONORRHEA CASES BETWEEN 2013 – 2017 WITH >550,000 CASES IN 2017 ALONE. N. GONORRHOEAE WREAKS HAVOC ON WORLD HEALTH CARE SYSTEMS CAUSING PELVIC INFLAMMATORY DISEASE, INFERTILITY AND ECTOPIC PREGNANCIES. THE BACTERIA CAN ALSO BE TRANSMITTED FROM MOTHER TO CHILD DURING BIRTH AND LEAD TO BLINDNESS. IF LEFT UNTREATED N. GONORRHOEAE CAN CAUSE GONOCOCCEMIA RESULTING IN SKIN INFECTION, ARTHRITIS OR ENDOCARDITIS. PATHOGENIC GONORRHEA STRAINS ARE INCREASINGLY RESISTANT TO COMMON FRONT-LINE ANTIBIOTICS. THE WHO SURVEILLANCE PROGRAM REPORTS RESISTANCE TO MOST AVAILABLE ANTIBIOTICS. RAMPANT RESISTANCE HAS CAUSED THE CDC AND THE WORLD HEALTH ORGANIZATION EACH TO CLASSIFY N. GONORRHOEAE AS A SUPERBUG AND A FUTURE WITH AN UNTREATABLE GONOCOCCAL INFECTION IS A REAL POSSIBILITY. THUS, THERE IS SIGNIFICANT UNMET NEED TO IDENTIFY NOVEL TARGETS AND MOLECULES WITH THERAPEUTIC POTENTIAL. STUDIES PROPOSED IN THIS APPLICATION BUILD UPON DISCOVERIES THAT FDA- APPROVED CARBONIC ANHYDRASE INHIBITORS (CAIS), SUCH AS ACETAZOLAMIDE AND ETHOXZOLAMIDE, DISPLAY POTENT ANTIMICROBIAL ACTIVITY, IN AN APPLICABLE CLINICAL RANGE, AGAINST N. GONORRHOEAE. CAIS, AND ANALOGS WE HAVE DESIGNED, ALSO HAVE NO ANTIMICROBIAL EFFECT ON COMMENSAL BACTERIA REDUCING THE POTENTIAL FOR PROBLEMATIC DYSBIOSIS CAUSED BY ANTIBIOTIC TREATMENT. WE HAVE SHOWN THAT THE MOLECULES EXHIBIT THEIR ANTIBIOTIC EFFECT BY INHIBITING THE CARBONIC ANHYDRASE FROM N. GONORRHOEAE AND HAVE VALIDATED N. GONORRHOEAE CARBONIC ANHYDRASE (NGCA) AS A VIABLE ANTI-GONOCOCCAL THERAPEUTIC TARGET. OUR TEAM HAS IMPROVED THE POTENCY OF THE CAI-BASED INHIBITORS FROM 4 ΜG/ML TO 0.5 ΜG/ML. THIS PROPOSAL WILL CONTINUE LEAD OPTIMIZATION OF CAI-BASED ANALOGS USING STRUCTURE-BASED DESIGN WHILE INCORPORATING MODIFICATIONS TO IMPROVE PERMEABILITY INTO THE GRAM-NEGATIVE CELL. MOLECULES WILL BE ASSESSED IN IN VITRO ANTIMICROBIAL ASSAYS AND PRIORITIZED ANALOGS WILL PROGRESS TO IN VITRO PHARMACOKINETIC (PK) AND PHARMACOLOGIC PROFILING. FINALLY, TOP PERFORMING ANALOGS WILL BE ASSESSED FOR IN VIVO EFFICACY IN VARIOUS GONORRHEA MOUSE MODELS AS WELL EVALUATED THE IN SAFETY AND PHARMACOKINETIC ASSAY TO SUPPORT FUTURE LEAD SELECTION AND INVESTIGATIONAL NEW DRUG ENABLING STUDIES.

FMRG: ECO: CYBER ENABLED TRANSFORMATION TO CIRCULAR SUPPLY CHAINS FOR SUSTAINABLE PHARMACEUTICAL MANUFACTURING NETWORKS -CURRENT PHARMACEUTICAL MANUFACTURING SYSTEMS FOLLOW THE LINEAR MODEL OF ?TAKE, MAKE, AND DISPOSE?. THIS MODEL IS NEITHER ECONOMICALLY NOR ENVIRONMENTALLY SUSTAINABLE. TO ENABLE FUTURE MANUFACTURING TO TRANSITION TO A CIRCULAR ECONOMY, MAKING MORE EFFICIENT USE OF MATERIALS THROUGH RECYCLING AND REPURPOSING, THERE IS A GROWING EMPHASIS ON MOVING TOWARDS CIRCULAR SUPPLY CHAINS (CSCS). MANY INDUSTRIES HAVE BEGUN TO CONVERT FROM CENTRALIZED BATCH MANUFACTURING TO AUTOMATION-DRIVEN CONTINUOUS MANUFACTURING THAT IS BASED ON ACTUAL, RATHER THAN PREDICTED, LEVELS OF DEMAND. YET, WHILE THIS REDUCES WASTE AT THE SINGLE-PLANT SCALE, IT IS NOT SUFFICIENT FOR THE CREATION OF A COMPLETE ZERO WASTE CSC INTEGRATED INDUSTRIAL ECOSYSTEM. MODELS DO NOT EXIST THAT CONNECT SINGLE-SCALE PLANTS TO THE LARGER NETWORK, MAKING IT IMPOSSIBLE TO ACCOUNT FOR FEEDBACK INTERACTIONS BETWEEN SINGLE-SCALE PROCESS INNOVATIONS AND EXISTING PROCESSES ACROSS THE MANUFACTURING NETWORK TO OPTIMIZE RESOURCE UTILIZATION. THE GOAL OF THIS PROJECT IS TO ENABLE THE DESIGN OF ZERO WASTE FUTURE PHARMACEUTICAL MANUFACTURING NETWORKS AT A MACROSCALE USING AN INTEGRATIVE, MULTIDISCIPLINARY APPROACH FOCUSED ON NOVEL PROCESS CHEMISTRY AND SEPARATION METHODS, MACROSCALE MODELING OF MANUFACTURING NETWORKS TO INTEGRATE NEW PROCESSES AT SCALE, AND PRICING OPTIMIZATION FOR COLLABORATIVE DECISION MAKING THROUGH DEDICATED CYBERINFRASTRUCTURE DEVELOPMENT. THE CYBERINFRASTRUCTURE DEVELOPED WILL AID IN UNDERSTANDING THE FEEDBACK LOOPS BETWEEN PLANT-SCALE AUTOMATED MANUFACTURING AND MACROSCALE MANUFACTURING NETWORKS IN MAKING OPTIMAL DECISIONS FOR ADOPTION OF RECYCLING PROCESSES AT SCALE AND REDESIGN OF MATERIAL FLOWS TOWARDS CSCS. TARGETED KEY CONTRIBUTIONS OF THE PROJECT ARE: 1) CREATING NOVEL MODULAR RECYCLING PROCESSES FOR WASTE MEDICINES TO ENABLE CSCS AND DIGITAL TWIN MODELS FOR THE FACILITIES, 2) AUTOMATING THE INTEGRATION OF NOVEL PROCESSES IN AN EXISTING NETWORK BY ADVANCING ALGORITHMS FOR MULTI- SCALE INTEGRATION AND ADVANCING CYBERINFRASTRUCTURE, AND 3) CREATING A DUAL PRICING MECHANISM AND ECONOMETRIC MODEL TO TRANSITION THE WHOLE SYSTEM TO A CSC BY FACILITATING WASTE EXCHANGE AND USE OF RECYCLED ACTIVE INGREDIENTS. THESE ADVANCEMENTS WILL PROVIDE A FRAMEWORK TO DRIVE INNOVATIONS IN MANUFACTURING PROCESSES AT THE SINGLE SCALE IN CONVERGENCE WITH MACROSCALE MANUFACTURING NETWORKS TO CREATE A ZERO-WASTE FUTURE MANUFACTURING SYSTEM. THE APPROACH OF INTEGRATING MODULAR MANUFACTURING PROCESSES AT THE RIGHT SCALE IN THE OVERALL NETWORK FOR ZERO WASTE PHARMACEUTICAL MANUFACTURING WILL BE GENERALIZABLE TO OTHER FUTURE MANUFACTURING NETWORKS. GRADUATE EDUCATION IN ENGINEERING WILL BE ENHANCED TO INCLUDE CONVERGENCE THINKING BY DEVELOPING A ?COMPUTATIONAL LAB? TO TRAIN INTERDISCIPLINARY STUDENTS IN PROCESS DESIGN THROUGH MACROSCALE NETWORK INTERACTIONS FOR ECONOMIC AND ENVIRONMENTAL SUSTAINABILITY. UNDERGRADUATES AND MINORITY STUDENTS WILL BE ENGAGED IN RESEARCH THROUGH PURDUE'S SURF PROGRAM AND EXISTING PURDUE PARTNERSHIPS WITH HBCUS AND PURDUE?S WOMEN IN ENGINEERING PROGRAM. FOR FUTURE WORKFORCE DEVELOPMENT IN PHARMACEUTICAL MANUFACTURING, THE PROJECT TEAM WILL PARTNER WITH PURDUE?S EXISTING BIOTECHNOLOGY INNOVATION AND REGULATORY SCIENCE PROGRAM AND OFFICE OF PROFESSIONAL PRACTICE TO TRANSLATE THE RESEARCH OUTCOMES INTO INDUSTRIAL PRACTICE TRAINING THROUGH WORKSHOPS FOR INDUSTRIAL STAKEHOLDERS, STUDENT INTERNSHIPS, AND PARTNERSHIPS WITH IVY TECH COMMUNITY COLLEGE. INTEGRATION THROUGH A WEB-BASED HUB OF CITIZEN DATA FOR USE IN DRIVING NETWORK DECISIONS WILL FACILITATE PARTICIPATION OF CITIZENS IN SUSTAINABLE FUTURE MANUFACTURING. THIS FUTURE MANUFACTURING AWARD IS SUPPORTED BY THE FOLLOWING NSF DIVISIONS/DIRECTORATES: CBET/ENG, CMMI/ENG, CHE/MPS, AND SBE. 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.

FMRG: ECO: CIRCULAR MANUFACTURING OF SUSTAINABLE BIOPLASTICS FROM HEMP-DERIVED BUILDING BLOCKS -DEVELOPING A MANUFACTURING-READY BIOPOLYMER WITH EXCEPTIONAL PROPERTIES AND MULTIPLE ROUTES TO RECYCLING AND DEGRADATION COULD ACCELERATE THE DISPLACEMENT OF LEGACY POLYMERS BASED ON PETROCHEMICALS, ULTIMATELY REDUCING GREENHOUSE GAS EMISSIONS AND LIMITING THE PROLIFERATION OF MICROPLASTICS THAT ARE DANGEROUS TO HUMANS AND THE ENVIRONMENT. THIS PROJECT WILL INVESTIGATE MATERIALS PARTIALLY DERIVED FROM HEMP FOR APPLICATIONS IN ELECTRONICS MANUFACTURING AND MEDICAL DEVICES. THE GENERAL AVAILABILITY THE SOURCE MATERIAL, HEMP, BENEFITS MANUFACTURERS BY SHORTENING SUPPLY CHAINS AND REDUCING SUPPLY CHAIN VULNERABILITIES AND BENEFITS SOCIETY BY REDUCING THE GENERATION, TRANSPORTATION, AND DISPOSAL OF TOXIC MATERIALS. CONTRASTING WITH OTHER BIOPOLYMERS THAT ARE GENERATED THROUGH THE FERMENTATION OF FOOD SOURCES (E.G. CORN), HEMP PROVIDES A FEEDSTOCK THAT DOES NOT COMPETE WITH FOOD. THE WORKFORCE DEVELOPMENT PLAN INCLUDES ENGAGEMENT STRATEGIES TO GUIDE STUDENTS STARTING FROM MIDDLE SCHOOL TO SECURING THEIR FIRST JOB IN MANUFACTURING. MIDDLE SCHOOL AND HIGH SCHOOL OUTREACH IS DESIGNED TO PROVIDE INSPIRATION AND POSITIVE, HANDS-ON EXPERIENCES TO ENTICE STUDENTS TOWARD STEM AND MANUFACTURING. THE ADDITIVE MANUFACTURING EXPERIENCE (AMX) PROGRAM PROVIDES OPPORTUNITIES FOR HIGH SCHOOL STUDENTS TO LEARN HANDS-ON MANUFACTURING SKILLS FROM INDUSTRY PROFESSIONALS THAT CAN BE LEVERAGED IN FINDING A FIRST JOB. TRAINING THROUGH RESEARCH AND COURSEWORK WILL PREPARE UNDERGRAD AND GRAD STUDENTS FOR FUTURE CAREERS IN SUSTAINABLE MANUFACTURING. THIS PROJECT WILL INVESTIGATE TWO HEMP-DERIVED DIOL MONOMERS WITH DIFFERING PROPERTIES IN COMBINATION WITH SEVERAL DICARBOXYLIC ACIDS. THE VARIETY OF COMBINATIONS WILL RESULT IN BIO-BASED POLYESTERS WITH WIDELY TUNABLE PROPERTIES. THIS WORK WILL SYNTHESIZE SEVERAL POLYESTER VARIATIONS AND TO EXPAND THE FUNDAMENTAL KNOWLEDGE OF STRUCTURE-PROPERTY RELATIONSHIPS TO FURTHER IMPROVE PERFORMANCE METRICS. STRUCTURE-PROCESSING KNOWLEDGE WILL BE DERIVED FROM CHARACTERIZATIONS SUCH AS MELT VISCOSITY, CRYSTALLIZATION RATE, AND SOLUBILITY. PROCESSING PARAMETERS WILL BE DETERMINED FOR MANUFACTURING APPROACHES INCLUDING MELT PROCESSING, 3D PRINTING, AND SOLUTION PROCESSING FROM GREEN SOLVENTS. AS ELECTRONICS ARE A LIKELY MARKET ENTRY POINT, THE INVESTIGATORS WILL STUDY THE PROTECTIVE PROPERTIES OF THE POLYMERS FOR CORRODIBLE METALS AND THE FACTORS THAT AFFECT THE DISPERSION STATE AND RESULTING MECHANICAL PROPERTIES AND ELECTRICAL CONDUCTIVITY IN COMPOSITE INKS. THERMAL REPROCESSING AND DEPOLYMERIZATION RECYCLING WILL BE CHARACTERIZED TO ENABLE CIRCULARITY OF THE POLYMER, AND DEGRADATION STUDIES WILL DETERMINE SAFETY IN THE ENVIRONMENT. PRINTED ELECTRONICS FOR MEDICAL DEVICES AND ENVIRONMENTAL SENSORS WILL PROVIDE DEMONSTRATION DEVICE PLATFORMS THAT LEVERAGE THE UNIQUE PROPERTIES OF THESE MATERIALS TO ATTRACT INDUSTRY ADOPTION. THIS FUTURE MANUFACTURING AWARD WAS SUPPORTED BY THE TECHNOLOGY, INNOVATION AND PARTNERSHIPS DIRECTORATE AND THE DIVISION OF CHEMISTRY AND DIVISION OF MATERIALS RESEARCH IN THE MATHEMATICAL AND PHYSICAL SCIENCES DIRECTORATE. 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.

MECHANISMS OF GENE-ENVIRONMENT INTERACTION IN DEVELOPMENTAL LEAD EXPOSURE LEADING TO ALZHEIMER'S DISEASE PHENOTYPES - PROJECT SUMMARY DEVELOPMENTAL EXPOSURE TO HEAVY METALS, SUCH AS LEAD (PB), CAUSES SYSTEMATIC DAMAGE TO THE CENTRAL NERVOUS SYSTEM AND IMPAIRS MANY NEUROLOGICAL TARGETS. SOME OF THESE BIOLOGICAL PERTURBATIONS, SUCH AS ALTERED SYNAPTIC PLASTICITY AND ENDOSOME TRAFFICKING, ARE SHARED WITH ALZHEIMER'S DISEASE (AD). EPIGENETIC MECHANISMS, GIVEN POTENCY AND LATENCY IN GENE REGULATION, OFFER A PLAUSIBLE ROUTE TO RELAY IMPACTS FROM EARLY-LIFE ENVIRONMENTAL EXPOSURE EVENTS TO AD. THE EXACT MOLECULAR MECHANISM, HOWEVER, REMAINS ELUSIVE. THE GOAL OF THIS PROPOSAL IS TO DEFINE THE EPIGENETIC MECHANISM CONTRIBUTING TO ALTERED SYNAPTIC PLASTICITY ARISING FROM DEVELOPMENTAL PB EXPOSURE ADDRESSING THE CONTRIBUTIONS OF GENE-BY-ENVIRONMENT (GXE) INTERACTIONS IN ACCELERATING THE PROGRESSION OF AD. OUR PRELIMINARY STUDIES AND PRIOR LITERATURE SUGGEST PERSISTENT ALTERATIONS IN SYNAPTIC PLASTICITY, PRIMARILY ARISING FROM CHANGES IN GLUTAMATE RECEPTORS, INCLUDING NMDAR AND AMPAR. ALTERATIONS IN ENDOSOMAL TRAFFICKING ARE ALSO HEAVILY IMPLIED. WE FORMULATED OUR CENTRAL HYPOTHESIS THAT DEVELOPMENTAL PB EXPOSURE ALTERS THE TRANSCRIPTION OF GLUTAMATE RECEPTORS VIA EPIGENETIC REGULATION AFFECTING SYNAPTIC PLASTICITY WITH THE EFFECTS EXACERBATED WHEN COUPLED WITH THE AD GENETIC RISK FACTOR, SORL1. THIS GXE INTERACTION COMPROMISES ENDOSOMAL TRAFFICKING AND GLUTAMATE RECEPTOR RECYCLING, WHICH EVENTUALLY LEADS TO THE ONSET OF AN AD-LIKE PHENOTYPE MANIFESTED BY PROTEIN AGGREGATION MARKERS. WE ADOPTED A MULTIPLEX MODEL INCLUDING CORTICAL NEURONS DERIVED FROM HUMAN INDUCED PLURIPOTENT STEM CELLS (HIPSCS) AND A ZEBRAFISH ANIMAL MODEL WITH AND WITHOUT A KNOWN LATE-ONSET AD (LOAD) RISK FACTOR (SORL1). WE DESIGNED OUR EXPERIMENTS TO DISSECT CONTRIBUTIONS FROM ENVIRONMENTAL (E), GENETIC (G), AND GXE DRIVEN EVENTS IN ALTERING SYNAPTIC PLASTICITY AND THE MANIFESTATION OF AD- LIKE PHENOTYPES. WE WILL TEST OUR HYPOTHESIS IN THREE AIMS. AIM 1 WILL ELUCIDATE THE IMPACT OF DEVELOPMENTAL PB EXPOSURE AND SORL1 EFFECTS ON NEURON SUSCEPTIBILITY OF PROTEIN AGGREGATES. AIM 2 WILL REVEAL THE MOLECULAR ORIGIN CONFERRING DEVELOPMENTAL PB NEUROTOXICITY TO AN AD-LIKE PHENOTYPE. AIM 3 WILL DEFINE SUBCELLULAR ALTERATIONS IN THE POST-SYNAPSE ASSOCIATED WITH AN AD-LIKE PHENOTYPE. COLLECTIVELY, WE WILL CURATE TIME-DEPENDENT INFORMATION ABOUT MOLECULAR CHANGES IN THE TRANSCRIPTOME AND EPIGENOME, ALONG WITH ALTERATIONS IN ULTRASTRUCTURE OF POST-SYNAPTIC SPINE. WE WILL USE THE AGGREGATED INFORMATION TO INFER CAUSATIVE RELATIONS AMONG DIFFERENT EVENTS BY ASSUMING EARLY EVENTS ARE LIKELY TO DRIVE LATE ONES. WE EXPECT THAT GXE INTERACTIONS ARISING FROM DEVELOPMENTAL PB EXPOSURE AND SORL1 MUTATION TO INDUCE A PHENOTYPE CLOSELY RESEMBLING AD, FOLLOWED BY SORL1 MUTATION ONLY, PB EXPOSURE IN WILD TYPE, AND UNTREATED WILD TYPE. FURTHERMORE, WE WILL REVEAL NOVEL TARGETS MEDIATING THE LATENT EFFECTS OF DEVELOPMENTAL PB EXPOSURE ON NEURODEGENERATION RISKS VIA MINING OF OUR DATASET AND VERIFICATION OF THE EFFICACY OF UNDERLYING EPIGENETIC PROFILES OF GLUTAMATE RECEPTORS IN ACCELERATING AD ONSET AND PROGRESSION RISKS. THE KNOWLEDGE GENERATED WILL ENLIGHTEN THE MOLECULAR MECHANISM OF PB NEUROTOXCITY AND CONNECTIONS OF EARLY LIFE PB EXPOSURE TO AD PROGRESSION ADDRESSING GOALS OF PAR-22-048.

OPTIMIZING A PERSONALIZED HEALTH APPROACH FOR VIRTUALLY TREATING HIGH-RISK CAREGIVERS DURING COVID-19 AND BEYOND - PROJECT SUMMARY/ABSTRACT WITH THE SPREAD OF COVID-19, PUBLIC HEALTH PRECAUTIONS HAVE REQUIRED PHYSICAL DISTANCING AND A VARIETY OF SHELTER-IN-PLACE ORDERS, CAUSING RAPID AND SUBSTANTIAL SHIFTS IN ALL ASPECTS OF FAMILY AND COMMUNITY LIFE. DATA FROM COVID-19, SUPPORTED BY EVIDENCE FROM PAST NATIONAL EMERGENCIES, SUGGEST CAREGIVERS ARE AT CLEAR RISK FOR SECONDARY HEALTH EFFECTS BECAUSE OF THE CURRENT PANDEMIC. COVID-19 HAS BEEN DESCRIBED AS A “PERFECT VECTOR FOR A MENTAL HEALTH EPIDEMIC” DUE TO THE ACCUMULATED EFFECTS OF PANDEMIC-RELATED FEAR, SOCIAL ISOLATION, POST-TRAUMATIC STRESS, AND MENTAL HEALTH TREATMENT BARRIERS. THESE CHANGES TO DAILY LIFE HAVE BEEN ESPECIALLY CHALLENGING FOR FAMILIES OF CHILDREN WITH NEUROGENETIC CONDITIONS (NGC), WHO EXPERIENCE HIGH LEVELS OF BASELINE STRESS, ARE PARTICULARLY VULNERABLE TO REDUCTIONS IN TARGETED THERAPEUTIC SERVICES, AND RELY ON MEDICAL AND EDUCATIONAL SERVICES THAT HAVE BEEN DISRUPTED BY COVID-19 RELATED CLOSURES. SPECIFICALLY, CAREGIVERS THEMSELVES ARE VULNERABLE TO STRESS-RELATED MENTAL AND PHYSICAL HEALTH CHALLENGES BECAUSE OF THE PANDEMIC; THEY RARELY RECEIVE TREATMENT FOR THEIR OWN MENTAL HEALTH NEEDS, AND ANY TREATMENTS THEY DO RECEIVE ARE TYPICALLY DISCONNECTED FROM THEIR CHILD'S CARE PLAN AND ARE DELIVERED BY PRACTITIONERS WITH LITTLE-TO-NO EXPERTISE IN THE NEEDS OF NGC FAMILIES. THESE HEALTH CARE GAPS ARE AMPLIFIED AMONG BLACK AND OTHER MINORITY FAMILIES. THE PROPOSED STUDY WILL ADDRESS THE NEEDS OF CAREGIVERS OF CHILDREN WITH NGC BY EXAMINING THE FEASIBILITY, EFFICACY, AND IMPACT OF A NOVEL NETWORK FOR DELIVERING PERSONALIZED TRIAGE AND DIGITAL TREATMENT. SPECIFICALLY, WE PROPOSE TO SCALE UP AND INTEGRATE A SERIES OF BRIEF, EVIDENCE BASED DIGITAL HEALTH INTERVENTIONS TO SUPPORT CAREGIVER MENTAL HEALTH, PARENTING SELF-EFFICACY, AND STRESS. SUPERVISED GRADUATE STUDENT TRAINEES WILL IMPLEMENT RIGOROUS, COST-EFFECTIVE, EVIDENCE-BASED INTERVENTIONS VIA TELEHEALTH. A KEY INNOVATION OF THIS WORK IS THAT WE WILL DEVELOP A PERSONALIZED HEALTH ROUTING ALGORITHM THAT MATCHES PARTICIPANTS WITH RELEVANT TREATMENTS USING BOTH CLINICAL INPUTS AND ECOLOGICAL MOMENTARY ASSESSMENT (EMA) DATA, BRIEF QUESTIONNAIRES “PINGED” TO CAREGIVER PHONES VIA A SMARTPHONE APP. A SECOND INNOVATION IS THAT WE WILL TEST THE EFFICACY OF PEER-TO-PEER COACHING IN ENHANCING TREATMENT UPTAKE AND OUTCOMES. COACHING WILL BE DELIVERED BY FELLOW NGC CAREGIVERS USING AN EVIDENCE-BASED MOTIVATIONAL INTERVIEWING PROTOCOL. BY THE END OF THE AWARD PERIOD, WE WILL HAVE GENERATED A NOVEL, SCALABLE, AND COST-EFFECTIVE SOLUTION FOR RAPIDLY MEETING ACUTE NEEDS FOR NGC CAREGIVERS THROUGH PERSONALIZED, DIGITAL DELIVERY OF EVIDENCE-BASED TREATMENTS. THIS MODEL CAN BE RAPIDLY SCALED FOR OTHER HIGH-RISK POPULATIONS DURING COVID-19 (E.G. FIRST RESPONDERS, TEACHERS, FRONTLINE WORKERS) AND FUTURE PUBLIC HEALTH CRISES. GIVEN SUBSTANTIAL UNMET NEEDS EXISTED AMONG NGC FAMILIES EVEN PRIOR TO COVID- 19, THIS PROTOCOL HAS POTENTIAL TO FUNDAMENTALLY SHIFT THE STATUS-QUO FOR HOW TREATMENT IS SELECTED AND ACCESSED IN NGC CAREGIVERS AND OTHER UNDERSERVED GROUPS, INCLUDING BEYOND THE COVID-19 PANDEMIC.

TARGETING PDGFR-B PROMOTER VACANCY G-QUADRUPLEX TO SUPPRESS GENE EXPRESSION - PROJECT SUMMARY TARGETING PDGFR-Β PROMOTER VACANCY G-QUADRUPLEX TO SUPPRESS GENE EXPRESSION OVEREXPRESSION OF PLATELET-DERIVED GROWTH FACTOR RECEPTOR Β (PDGFR-Β) IS AN IMPORTANT FACTOR IN HUMAN CANCERS AND INFLAMMATORY DISEASES. THE PDGFR-Β SIGNALING PATHWAY IS A VALIDATED THERAPEUTIC TARGET FOR CANCER TREATMENT. PROTEIN KINASE INHIBITORS TARGETING PDGFR-Β HAVE BEEN EVALUATED IN CLINICAL TRIALS, HOWEVER, THEY LACK SPECIFICITY AND ARE INEFFECTIVE AGAINST PDGFR-Β MUTANTS. G-QUADRUPLEX IS A GLOBULAR DNA SECONDARY STRUCTURE AND A NEW CLASS OF MOLECULAR TARGETS FOR ANTICANCER DRUGS. THE HUMAN PDGFR-Β PROMOTER HAS A G-QUADRUPLEX- FORMING REGION THAT FUNCTIONS AS A TRANSCRIPTIONAL SILENCER AND IS TARGETABLE BY SMALL MOLECULES. THE PDGFR-Β PROMOTER G-QUADRUPLEXES DIFFER SIGNIFICANTLY FROM THE CANONICAL G-QUADRUPLEXES WITH THREE COMPLETE G-TETRADS, SUCH AS THOSE FORMED IN MYC AND VEGF PROMOTER SYSTEMS. IN CONTRAST, WE FOUND THAT THE G-QUADRUPLEX FORMED IN THE PDGFR-Β PROMOTER ADOPTS A UNIQUE BROKEN-STRAND STRUCTURE WHICH READILY FORMS A VACANCY G-QUADRUPLEX (VG4) WITH AN INCOMPLETE G-TETRAD THAT CAN BE FILLED-IN BY AN EXTERNAL GUANINE DERIVATIVE. FURTHERMORE, WE SHOWED THAT THE GUANINE-FILL-IN-VG4 CAN BE STABILIZED BY THE MEDICINAL NATURAL PRODUCT BERBERINE AND WE DETERMINED THEIR TERNARY COMPLEX STRUCTURE BY NMR. SIGNIFICANTLY, OUR STRUCTURE INDICATES THAT THE UNIQUE PDGFR- Β VG4 PRESENT A SPECIFIC RECOGNITION SITE FOR A BERBERINE-GUANINE CONJUGATE WITH A BERBERINE LINKED WITH A GUANINE MOIETY. THEREFORE, WE HYPOTHESIZE THAT THE UNIQUE VG4 FORMED IN THE PDGFR-Β PROMOTER CAN BE SELECTIVELY TARGETED BY BERBERINE-GUANINE CONJUGATES OVER CANONICAL G-QUADRUPLEXES TO SUPPRESS PDGFR-Β TRANSCRIPTION IN CANCER CELLS. EXCITINGLY, BASED ON OUR DETERMINED NMR STRUCTURE, WE HAVE SUCCESSFULLY SYNTHESIZED TWO BERBERINE-GUANINE CONJUGATES THAT BIND THE PDGFR-Β VG4 WITH HIGH-AFFINITY AND SPECIFICITY USING THE G-FILL-IN RECOGNITION MODE, AND CAN GET INTO CANCER CELLS AND LOWER PDGFR-Β LEVELS. THE SPECIFIC AIMS ARE: 1) STRUCTURAL CHARACTERIZATION OF BERBERINE-GUANINE CONJUGATES IN COMPLEX WITH THE PDGFR-Β PROMOTER VG4. 2) DESIGN AND SYNTHESIZE BERBERINE-GUANINE CONJUGATES USING STRUCTURE-BASED RATIONAL APPROACH THAT SPECIFICALLY RECOGNIZE THE UNIQUE PDGFR-Β PROMOTER VG4 FOR EFFECTIVE GENE SUPPRESSION. 3) DETERMINE THE EFFECTS OF BERBERINE-GUANINE CONJUGATES ON PDGFR-Β GENE EXPRESSION AND ACTIVITIES IN PDGFR-Β–DRIVEN CANCERS. THE EXPECTED OUTCOME OF THIS WORK IS A STRUCTURE-BASED RATIONAL DESIGN AND DEVELOPMENT OF NOVEL BERBERINE-GUANINE CONJUGATES THAT SPECIFICALLY RECOGNIZE THE UNIQUE PDGFR-Β PROMOTER VG4 AND SUPRESS PDGFR-Β GENE EXPRESSION. THE LONG- TERM GOAL OF THIS PROPOSAL IS TO DEVELOP LEAD COMPOUNDS OF BERBERINE-GUANINE CONJUGATES FOR FUTURE PRECLINICAL TESTING. THE RESULTS WILL HAVE AN IMPORTANT POSITIVE IMPACT BECAUSE THEY LAY THE GROUNDWORK TO DEVELOP NOVEL GUANINE CONJUGATES FOR SPECIFIC TARGETING OF THE PDGFR- SILENCER ELEMENT. FURTHER, THE TARGETING COMPOUNDS DEVELOPED CAN SERVE AS MOLECULAR PROBES TO INVESTIGATE PROTEIN INTERACTIONS OF THE UNIQUE PDGFR-Β PROMOTER VG4 AND PROVIDE MECHANISTIC UNDERSTANDING OF PDGFR-Β GENE TRANSCRIPTIONAL REGULATION.

HAVING OPPORTUNITIES PROMOTES EXCELLENCE: DEVELOPING SCHOLAR IDENTITIES AMONG UNDERSERVED YOUTH WITH GIFTS AND TALENTS

RATIONAL OPTIMIZATION OF COMBINATORIAL THERAPIES FOR THE TREATMENT OF RARE CYSTIC FIBROSIS VARIANTS - ABSTRACT CYSTIC FIBROSIS (CF) IS A LETHAL GENETIC DISEASE THAT CURRENTLY AFFECTS ~100,000 PEOPLE WORLDWIDE. CF IS CAUSED BY A SPECTRUM OF LOSS-OF-FUNCTION MUTATIONS THAT COMPROMISE THE BIOGENESIS AND/ OR FUNCTION OF THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) ION CHANNEL, MOST OF WHICH ENHANCE ITS MISFOLDING AND DEGRADATION. RECENT DRUG DISCOVERY EFFORTS HAVE YIELDED A SUITE OF APPROVED SMALL MOLECULE “CORRECTORS” THAT ENHANCE THE EXPRESSION OF MISFOLDED CFTR VARIANTS AND “POTENTIATORS” THAT RESTORE CONDUCTANCE TO CFTR VARIANTS WITH DEFECTIVE GATING. COMBINATIONS OF THESE MOLECULES HAVE RECENTLY REVOLUTIONIZED THE TREATMENT OF THE ~90% OF CF PATIENTS BEARING AT LEAST ONE COPY OF THE WELL-STUDIED F508 CFTR VARIANT, WHICH IS HIGHLY PENETRANT AMONG CAUCASIANS. HOWEVER, THE EFFICACY OF CURRENT COMBINATORIAL THERAPIES VARIES WIDELY AMONG THE ~10% OF PATIENTS BEARING DIVERSE COMBINATIONS OF RARE, UNCHARACTERIZED CF VARIANTS WITH DIVERGENT PHARMACOLOGICAL PROPERTIES (“THERATYPE”). EFFORTS TO EXPAND THE LABELS OF CURRENT THERAPEUTICS AND MAXIMIZE THE NUMBER OF TREATABLE CF GENOTYPES, IN PARTICULAR AMONGST NON-WHITE POPULATIONS, ARE CONSTRAINED BY THE LARGE NUMBER OF CF VARIANTS AND THE LIMITED THROUGHPUT OF CURRENT METHODS. IDENTIFYING RARE CF VARIANTS THAT RESPOND TO THERAPEUTIC COCKTAILS IS LIKELY TO BECOME EVEN MORE CHALLENGING AS NEW CORRECTORS AND/ OR POTENTIATORS GAIN APPROVAL. ADDRESSING THIS CHALLENGE REQUIRES NEW TECHNIQUES THAT ENABLE EFFICIENT BIOCHEMICAL AND/ OR PHARMACOLOGICAL PROFILING OF RARE CF VARIANTS. IN THE FOLLOWING, WE PROPOSE TO ADDRESS THIS CHALLENGE WITH A UNIQUE FUSION OF EMERGING GENETIC, BIOCHEMICAL, AND COMPUTATIONAL METHODS. WE SHOW HOW DEEP MUTATIONAL SCANNING (DMS) CAN BE USED TO COMPARE THE EFFECTS OF CORRECTORS ON THE EXPRESSION OF HUNDREDS OF VARIANTS IN PARALLEL. OUR PRELIMINARY FINDINGS PROVIDE AN UNPRECEDENTED GLIMPSE OF THE DIVERGENT THERATYPES OF CF VARIANTS WHILE IDENTIFYING NUMEROUS VARIANTS WITH UNIQUE BIOCHEMICAL AND/ OR PHARMACOLOGICAL PROPERTIES. WE FIRST PROPOSE TO EXPAND ON THESE INVESTIGATIONS IN ORDER TO MEASURE THE RESPONSE OF THE COMPLETE SET OF CFTR2 MISSENSE VARIANTS TO A PANEL OF STRUCTURALLY DIVERSE CORRECTOR MOLECULES. WE WILL THEN CHARACTERIZE THE INTERACTOMES OF VARIANTS WITH DISTINCT CORRECTOR RESPONSES TO IDENTIFY CFTR INTERACTIONS THAT ANTAGONIZE THE EFFECTS OF THESE SMALL MOLECULES. WE WILL THEN FUSE CRISPR/ CAS9 TECHNOLOGY WITH DMS TO DETERMINE HOW THESE INTERACTIONS IMPACT THE SPECTRUM OF CF VARIANT THERATYPES. USING STATE-OF-THE-ART STRUCTURAL MODELING APPROACHES, WE WILL THEN IDENTIFY STRUCTURAL DEFECTS IN THE CFTR PROTEIN THAT ARE ASSOCIATED WITH THE FORMATION OF ANTAGONISTIC INTERACTIONS AND DEVIATIONS IN CFTR VARIANT THERATYPE. WE WILL THEN UTILIZE MACHINE LEARNING TO CLASSIFY CF VARIANTS BASED ON THEIR OBSERVED PHARMACOLOGICAL PROPERTIES. FINALLY, WE WILL ASSESS THE EFFECTS OF APPROVED CORRECTORS ON THE FUNCTIONAL PROPERTIES OF PREVIOUSLY UNCHARACTERIZED VARIANTS USING INDUSTRY-STANDARD SHORT-CIRCUIT CURRENT ANALYSIS IN FISCHER RAT THYROID AND HUMAN AIRWAY EPITHELIAL CELLS. TOGETHER, THESE INVESTIGATIONS WILL HELP EXPAND THE LIST OF TREATABLE CF GENOTYPES AND PROVIDE NEW TOOLS TO OPTIMIZE THE TARGETING OF CF DRUGS.

THE PURPOSE OF THIS AWARD IS TO DEVELOP SURVEILLANCE TOOLS AND STRATEGIES FOR THE RAPID DETECTION AND CHARACTERIZATION OF NEW VARIANTS OF SARS-COV-2 TO SUPPORT AN EARLY WARNING SYSTEM TO PREVENT OR LIMIT FUTURE SARS COV-2 OUTBREAKS. THIS RESEARCH PROJECT AIMS TO DEVELOP A USER-FRIENDLY SURVEILLANCE TOOL THAT CAN DETECT SARS-COV-2 IN ANY ANIMAL SPECIES, BE USED IN THE FIELD, AND REPORT THE RESULTS IN A SIMPLE DASHBOARD. THE PROJECT TEAM PLANS TO COLLECT ORONASAL SAMPLES FROM 38 SPECIES OF ANIMALS, INCLUDING WILDLIFE (CAPTIVE AND FREE RANGE), FARMED ANIMALS, AND COMPANION ANIMALS, ACROSS THE UNITED STATES. THEY WILL THEN REFINE AND TEST A MOLECULAR METHOD FOR DETECTING AND SEQUENCING SARS-COV-2 IN THESE SAMPLES AND DEVELOP A DASHBOARD TO REPORT THE RESULTS. THE RESULTING TOOL WILL ALLOW FOR LOW-COST, RAPID, AND USER-FRIENDLY SURVEILLANCE OF ANIMALS IN THE FIELD, PROVIDING VALUABLE INFORMATION THAT MAY INFORM MANAGEMENT STRATEGIES IF/WHEN SARS-COV-2 INFECTION RATES BEGIN TO CLIMB, OR NEW (POTENTIALLY MORE VIRULENT) STRAINS EMERGE. THE RECIPIENT MUST MEET THE OBJECTIVES AND DELIVERABLES STATED IN THEIR WORK PLAN AND MUST COMPLETE QUARTERLY FINANCIAL AND PERFORMANCE REPORTS AND A FINAL ACCOMPLISHMENT REPORT. BY ENABLING BETTER TRACKING OF SARS-COV-2 IN ANIMALS, THE PROJECT AIMS TO HELP WILDLIFE VETERINARIANS/BIOLOGISTS, EPIDEMIOLOGISTS, AND ANIMAL AND PUBLIC HEALTH AGENCIES FROM A VARIETY OF ENVIRONMENTS (TRIBAL/STATE/FEDERAL LANDS, FARMS, HOMES) IN UNDERSTANDING THE TRANSMISSION OF THE VIRUS FROM ANIMALS TO OTHER ANIMALS AND HUMANS. THE TOOL'S ACCESSIBILITY IN RESOURCE-LIMITED SETTINGS WILL MAKE IT PARTICULARLY USEFUL FOR NATIVE AMERICAN AND ALASKA NATIVE TRIBES, DEPARTMENTS OF NATURAL RESOURCES, U.S. GEOLOGICAL SURVEY, AND ANIMAL HEALTH AGENCIES. NO SUBAWARDS ARE PLANNED.

LOW-TEMPERATURE ELECTROCATALYTIC MANUFACTURING OF ESSENTIAL CHEMICAL BUILDING BLOCKS

COLLABORATIVE RESEARCH: CPS: FRONTIER: CHORUS: RESILIENT DISTRIBUTED CPS THROUGH RATIONAL AND DYNAMIC DECISION-MAKING AMONG MULTIPLE STAKEHOLDERS -CYBER-PHYSICAL SYSTEMS (CPS) ARE TYPICALLY COMPOSED OF INTERCONNECTED HARDWARE AND SOFTWARE COMPONENTS, WHICH INDIVIDUALLY MAY NOT BE INHERENTLY HIGHLY RELIABLE OR SECURE. HOWEVER, SEVERAL CPS APPLICATIONS DEMAND A HIGH DEGREE OF SAFETY, SECURITY, AND RELIABILITY. THUS, THE FUNDAMENTAL PROBLEM IS CONSTRUCTING HIGHLY DEPENDABLE CPS APPLICATIONS FROM BUILDING BLOCKS THAT ARE, IN THEMSELVES, NOT INHERENTLY RELIABLE. THERE HAS BEEN ENORMOUS PROGRESS MADE IN UNDERSTANDING AND PATCHING VARIOUS CLASSES OF VULNERABILITIES IN LARGE-SCALE DISTRIBUTED CPS. HOWEVER, THESE EFFORTS AT DESIGNING AND OPERATING RESILIENT CPS HAVE OFTEN BEEN STYMIED BY THE LACK OF UNDERSTANDING OF THE IMPACT OF ANY PERTURBATION TO THE OVERALL SYSTEM, UNDER THE ECONOMIC AND POLICY CONSTRAINTS INVOLVED IN ANY REALISTIC REAL-WORLD CPS. WE DEFINE PERTURBATIONS AS FAILURES DUE TO: (1) UNINTENDED ERRORS IN HARDWARE/SOFTWARE, (2) SECURITY ATTACKS, (3) UNEXPECTED INTERACTIONS AMONG CYBER-PHYSICAL AND HUMAN ELEMENTS INCLUDING NATURAL DISASTERS, AND (4) INCOMPLETE COOPERATION AMONG STAKEHOLDERS. IN THIS PROJECT, WE ADDRESS THESE SHORTCOMINGS TO CHALLENGES TO CREATE RESILIENT, LARGE-SCALE CPS THROUGH OUR CHORUS FRONTIER AWARD. CHORUS WILL DEVELOP RIGOROUS, SCIENTIFIC MECHANISMS TO ENABLE CPS RESILIENCE AGAINST A LARGE UNIVERSE OF PERTURBATIONS. OUR APPLICATION DOMAIN IS CONNECTED AND AUTONOMOUS TRANSPORTATION SYSTEMS (CATS) AND THUS, THE BENEFITS OF CHORUS WILL BE DEMONSTRATED THROUGH IMPROVEMENTS IN SAFETY AND SECURITY IN THIS DOMAIN. WE WILL ACHIEVE GOALS OF CHORUS THROUGH THREE INTERACTING INTELLECTUALLY CHALLENGING THRUSTS IN THE PROJECT. THRUST 1 IS ON MODELING WHICH WILL CREATE EXECUTABLE SPECIFICATIONS OF CYBER, PHYSICAL, AND HUMAN ASSETS, THEIR INTERCONNECTIONS, AND THE ECONOMIC AND POLICY CONSTRAINTS. THE MODELS WILL CAPTURE VARIOUS STAKEHOLDERS IN THE SYSTEM AND THEIR DEGREE OF INFORMATION SHARING AND COOPERATION IN DEFENSE OF THE TARGET CPS. THRUST 2 IS CENTERED ON PROACTIVE PLANNING AND DEPLOYMENT. WE WILL DEVELOP RIGOROUS GAME-THEORETIC FORMULATIONS TO MODEL THE SPREAD OF PERTURBATIONS (NATURAL AND MAN-MADE), THEIR EFFECTS, AND THE APPROPRIATE RESOURCE ALLOCATIONS THAT CAN BE APPLIED FOR RESILIENCE AT THE PLANNING STAGE, I.E., PRIOR TO SYSTEM DEPLOYMENT. WE WILL ALSO CONSIDER WHICH DEFENSIVE INVESTMENTS ARE FEASIBLE UNDER A RATIONAL VERSUS A BOUNDED RATIONAL BEHAVIORAL MODEL OF THE STAKEHOLDERS. THRUST 3 FOCUSES ON RUNTIME DISTRIBUTED DETECTION AND RESPONSE. WE WILL DETERMINE, AT RUNTIME, THE SECURITY STATE OF THE SYSTEM, THROUGH NOVEL USES OF EXISTING SENSORS IN THE SYSTEM EVEN THOUGH THEY ARE IMPERFECT. THIS WILL THEN TRIGGER THE RESPONSE MECHANISMS, WHICH WILL BE PROVEN TO BE APPROXIMATELY OPTIMAL, THROUGH ANALYSIS AND EXPERIMENTATION. IN TERMS OF BROADER IMPACT, THE GREATEST IMPACT WILL BE THAT CPS OWNERS WILL GAIN A HIGHER DEGREE OF TRUST IN THE OPERATION OF THE CPS AND POLICY-MAKERS WILL UNDERSTAND WHAT LEVEL OF COOPERATION AMONG MULTIPLE STAKEHOLDERS IN A CPS TO INCENTIVIZE. WE WILL CREATE COMPELLING DEMONSTRATIONS OF CHORUS ON A CONNECTED VEHICLE TESTBED DISTRIBUTED BETWEEN OUR ACADEMIC INSTITUTIONS AND OUR INDUSTRIAL PARTNER GM. WE WILL ALSO ORGANIZE AN ANNUAL STUDENT SECURITY COMPETITION AND DEVELOP TWO MOOCS, BOTH HAVING FOUNDATIONAL MATERIAL ON RESILIENT CPS AND ONE FOCUSING MORE ON THE CATS APPLICATION DOMAIN. 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.

IDEAS LAB: USPRD: PROGRAMMABLE SMALL MOLECULE BIOSYNTHESIS -PROGRAMMABLE SMALL MOLECULE BIOSYNTHESIS THIS PROJECT AIMS TO DEVELOP NEW BIOPLASTICS WITH DIVERSE PROPERTIES. THE TEAM WILL COMPUTATIONALLY DESIGN COMPLEX ENZYMES WITHIN ENGINEERED BACTERIA TO PRODUCE NOVEL, STURDY BIOPLASTICS THAT CAN WITHSTAND HIGH TEMPERATURES AND BE EASILY RECYCLED INTO THEIR ORIGINAL COMPONENTS?OR BIODEGRADED AND COMPOSTED IF DISCARDED IN A LANDFILL. THESE ADVANCES WILL STRENGTHEN SUPPLY CHAIN RESILIENCE THROUGH THE BIOECONOMY AND OPEN NEW DIRECTIONS IN DOMESTIC MANUFACTURING. BEYOND SCIENTIFIC ADVANCEMENTS, THE INITIATIVE WILL INCLUDE OUTREACH TO UNDERGRADUATE STUDENTS TO TRAIN THE NEXT GENERATION OF BIOTECHNOLOGISTS, THE DEVELOPMENT OF NEW WORKSHOPS ON PROTEIN DESIGN AND ITS REAL-WORLD APPLICATIONS, AND WILL PROVIDE OPEN-SOURCE TOOLS FOR FUTURE INNOVATIONS IN BIOMANUFACTURING. THIS INTERDISCIPLINARY EFFORT SEEKS TO ENGINEER POLYKETIDE SYNTHASES (PKSS) TO PRODUCE MONOMERS FOR POLYHYDROXYALKANOATES (PHAS) WITH ENHANCED THERMAL STABILITY AND RECYCLABILITY. THE FOCUS IS ON CREATING HYBRID PKSS CAPABLE OF SYNTHESIZING GEM-DIMETHYLATED PHAS (GDPHAS) THROUGH ADVANCED COMPUTATIONAL PROTEIN DESIGN, ADDRESSING THE LONGSTANDING CHALLENGE OF SLOW TURNOVER RATES AND POOR DOMAIN INTERACTIONS IN ENGINEERED PKSS. RESEARCHERS WILL IDENTIFY AND RECOMBINE PKS DOMAINS TO ENABLE PROGRAMMABLE BIOSYNTHESIS OF 3-HYDROXYACIDS WITH TUNABLE PROPERTIES, LEVERAGING DEEP LEARNING-POWERED DESIGN TOOLS. THESE TOOLS WILL OPTIMIZE ENZYME FUNCTIONALITY, REPROGRAM ACTIVE SITES, AND ENHANCE TRANSIENT PROTEIN-PROTEIN INTERACTIONS WITHIN PKSS. EXPERIMENTAL DESIGN-BUILD-TEST-LEARN CYCLES WILL VALIDATE THE DESIGNS. ENGINEERED PKSS INTEGRATED WITH PHA SYNTHASES WILL ENABLE BACTERIAL PRODUCTION OF PHAS RESISTANT TO HIGH TEMPERATURES AND SUITABLE FOR DEPOLYMERIZATION, ALLOWING EITHER BIODEGRADATION OR RECYCLING. THE PROJECT WILL DEVELOP RETROSYNTHESIS WORKFLOWS FOR PKS PATHWAYS, COMPUTATIONAL TOOLS FOR PROTEIN DESIGN, AND METHODOLOGIES FOR HIGH-GC DNA SYNTHESIS. BY MAKING THESE INNOVATIONS BROADLY ACCESSIBLE, THE WORK WILL ADVANCE ENZYME ENGINEERING, SUPPORT STEM EDUCATION, AND FOSTER DOMESTIC BIOMANUFACTURING. 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.

IMPACT OF HYPOXIA ON LIPID METABOLISM IN OBESITY-DRIVEN BREAST CANCER PROGRESSION - PROJECT SUMMARY WHILE SIGNIFICANT EVIDENCE HAS DEMONSTRATED THAT OBESITY INCREASES THE RISK OF METASTASIS, THE MOLECULAR MECHANISMS BY WHICH OBESITY CONTRIBUTES TO THE METASTATIC PROGRESSION OF BREAST CANCER ARE UNCLEAR. FURTHERMORE, RECENT RESEARCH IN CANCER DEVELOPMENT AND PROGRESSION HAS HIGHLIGHTED THE ROLE OF HYPOXIA AND DYSREGULATED LIPID METABOLISM. RESEARCH FROM OUR TEAM AND OTHERS DEMONSTRATE THAT LIPID ACCUMULATION, WHICH IS ASSOCIATED WITH REDUCED PATIENT OUTCOMES, IS GREATER IN METASTASES COMPARED TO PRIMARY TUMORS. FURTHERMORE, HYPOXIA, WHICH IS INCREASED IN OBESITY IN THE PRIMARY TUMOR, LEADS TO SUSTAINED INCREASE IN THE EXPRESSION OF SPECIFIC GENES AFTER REOXYGENATION, A HYPOXIC MEMORY. OUR RESULTS DEMONSTRATE THAT HYPOXIC MEMORY RESULTS IN THE EXPRESSION OF FATTY ACID SYNTHASE (FASN), WHICH IS THE RATE-LIMITING STEP IN FATTY ACID SYNTHESIS, AND PYRUVATE CARBOXYLASE (PC), WHICH WE HAVE SHOWN PROVIDES OXIDATIVE STRESS PROTECTION. IN ADDITION, THE INFLAMMATORY CYTOKINE INTERLEUKIN-6 (IL-6), WHICH IS ELEVATED IN OBESITY, ENHANCES THE EXPRESSION OF CPT1A, THE RATE-LIMITING STEP IN FATTY ACID OXIDATION (FAO) TO SUPPLY ENERGY. OUR PRELIMINARY DATA SHOW THAT THE EXPRESSION OF THESE THREE PROTEINS AND THEIR FUNCTIONAL CONSEQUENCES OF INCREASED FATTY ACID SYNTHESIS AND FAO ARE ELEVATED IN METASTASES COMPARED TO PRIMARY TUMORS. THUS, OUR PRELIMINARY RESULTS SUGGEST THAT HYPOXIA MAY SET THE STAGE FOR DYSFUNCTIONAL LIPID METABOLISM, WHERE INCREASED LIPID SYNTHESIS AND UTILIZATION OCCUR CONCURRENTLY WITH A BALANCE TOWARDS LIPID ACCUMULATION. HOWEVER, THE IMPACT OF DYSFUNCTIONAL LIPID METABOLISM IN OBESITY-DRIVEN METASTASIS IS UNKNOWN DESPITE THE SUPPORTING EVIDENCE THAT HYPOXIA AND IL-6 ARE ENHANCED IN OBESITY. IN THE PROPOSED STUDIES, THE RESEARCH TEAM WILL UTILIZE MULTIPLE MOUSE MODELS OF OBESITY AND METASTATIC BREAST CANCER TO EVALUATE THE MECHANISTIC BASIS BY WHICH HYPOXIC MEMORY AND IL-6 INTERACT TO STIMULATE OBESITY-DRIVEN BREAST CANCER METASTASIS. THEY WILL TEST THE HYPOTHESIS THAT OBESITY-ASSOCIATED INCREASES IN HYPOXIC MEMORY AND PROINFLAMMATORY IL-6 SIGNALING WORK IN TANDEM TO INCREASE FA ACCUMULATION (FASN), FAO (CPT1), AND CELL SURVIVAL (PC) TO ENHANCE METASTASES. THESE HYPOTHESES WILL BE TESTED THROUGH THE COMPLETION OF THE FOLLOWING TWO AIMS: 1) DETERMINE THE IMPACT OF HYPOXIC MEMORY ON LIPID ACCUMULATION IN OBESITY-DRIVEN METASTASIS, AND 2) ESTABLISH THE INTERACTION OF HYPOXIC MEMORY WITH CHRONIC INFLAMMATION IN OBESITY-DRIVEN METASTASIS. THESE STUDIES WILL PROVIDE FOUNDATIONAL EVIDENCE FOR DEVELOPING TARGETED STRATEGIES TO MITIGATE OBESITY-DRIVEN METASTATIC BREAST CANCER.

COOLSCREW: HOLISTIC OPTIMIZATION OF A HIGH TEMPERATURE HEAT PUMP SYSTEM WITH INTERNALLY COOLED SCREW COMPRESSORS

FIRE-WUI: COMMUNITY RESILIENCE ASSESSMENT FRAMEWORK FOR WILDFIRES USING MULTI-RESOLUTION DIGITAL TWINS -WILDFIRES POSE A GROWING THREAT TO COMMUNITIES ACROSS THE US, PARTICULARLY IN AREAS WHERE HOMES AND NATURAL LANDSCAPES MEET, KNOWN AS THE WILDLAND-URBAN INTERFACE (WUI). EACH YEAR, MORE THAN 60,000 WILDFIRES OCCUR IN THE US, OFTEN RESULTING IN TRAGIC LOSS OF LIFE, DESTRUCTION OF HOMES, AND SEVERE ECONOMIC DISRUPTION. EFFECTIVE WILDFIRE RESPONSE AND PREVENTION EFFORTS ARE HINDERED BY A LACK OF DETAILED, UP-TO-DATE INFORMATION ABOUT VEGETATION AND BUILDINGS IN THESE HIGH-RISK AREAS. TO ADDRESS THESE CHALLENGES, THIS PROJECT WILL DEVELOP A FRAMEWORK THAT CREATES DETAILED, 3D DIGITAL REPRESENTATIONS, REFERRED TO HERE AS DIGITAL TWINS, OF BOTH NATURAL AND BUILT ENVIRONMENTS. THESE DIGITAL TWINS WILL PROVIDE ACCURATE, LOCATION-SPECIFIC INFORMATION NEEDED TO SIMULATE HOW FIRES SPREAD AND ENABLE THE DEVELOPMENT OF MORE EFFECTIVE MITIGATION STRATEGIES. THE INTELLECTUAL MERIT OF THIS PROJECT INCLUDES THE CREATION OF A GROUNDBREAKING FRAMEWORK FOR GENERATING SCALABLE, MULTI-RESOLUTION DIGITAL TWINS THAT COMBINE DATA FROM SATELLITES, DRONES, AND GROUND SENSORS. BY INTEGRATING AI AND ADVANCED MODELING TECHNIQUES, THE SYSTEM WILL ENHANCE THE UNDERSTANDING OF FIRE BEHAVIOR IN WUI ENVIRONMENTS AND SUPPORT MORE ACCURATE FIRE-SPREAD PREDICTIONS. THIS RESEARCH REPRESENTS A CONVERGENT AND INTERDISCIPLINARY APPROACH THAT COMBINES GEOSPATIAL SCIENCE, WILDFIRE MODELING, AND DATA ANALYTICS IN NOVEL WAYS STILL UNREALIZED AT THIS SCALE. THE BROADER IMPACTS OF THIS PROJECT ARE SIGNIFICANT. THE DIGITAL TWIN FRAMEWORK WILL HELP IMPROVE COMMUNITY RESILIENCE AND PREPAREDNESS AGAINST WILDFIRES BY PROVIDING FIRST RESPONDERS, PLANNERS, AND POLICYMAKERS WITH THE TOOLS TO MAKE FASTER, DATA-DRIVEN DECISIONS. THE SYSTEM IS DESIGNED TO SCALE NATIONWIDE AND CAN BE ADAPTED TO OTHER TYPES OF NATURAL DISASTERS. THE PROJECT WILL ALSO PREPARE THE NEXT GENERATION OF EXPERTS THROUGH INTERDISCIPLINARY EDUCATION AND TRAINING PROGRAMS, INCLUDING NEW COURSES, ONLINE LEARNING MODULES, MENTORSHIP, AND PROFESSIONAL TRAINING DEVELOPED IN COLLABORATION WITH INDUSTRY ORGANIZATIONS. THESE EFFORTS WILL ENSURE A MORE KNOWLEDGEABLE WORKFORCE READY TO CONFRONT THE COMPLEX CHALLENGES OF WILDFIRE MANAGEMENT. THE ?COMMUNITY RESILIENCE ASSESSMENT FRAMEWORK AGAINST WUI-FIRES USING MULTI-RESOLUTION DIGITAL TWINS ? (CRAFT)? PROJECT AIMS TO DEVELOP A SCALABLE, DYNAMIC DIGITAL TWIN FRAMEWORK TO SUPPORT WILDFIRE MODELING AND MITIGATION IN THE WUI. CRAFT WILL INTEGRATE HETEROGENEOUS GEOSPATIAL DATA FROM SATELLITE, AERIAL, AND GROUND-BASED PLATFORMS USING AI-BASED SUPER-RESOLUTION, GENERATIVE MODELING, AND QA/QC PROTOCOLS TO CREATE MULTI-RESOLUTION, CONTINUOUSLY UPDATED 3D MODELS. THESE DIGITAL TWINS WILL FEED INTO ENHANCED FIRE-SPREAD MODELS TO IMPROVE PREDICTION ACCURACY AND INVESTIGATE THE TRADE-OFF AMONG RESOLUTION, PERFORMANCE, AND COMPUTATIONAL COMPLEXITY. THE IMPROVED MODELS ARE THEN USED TO EVALUATE MITIGATION STRATEGIES. VALIDATION WILL OCCUR THROUGH TESTBEDS WITH DISTINCT CHARACTERISTICS IN THE U.S. EASTERN AND WESTERN WUI REGIONS. EDUCATIONAL COMPONENTS WILL SUPPORT WORKFORCE DEVELOPMENT IN GEOSPATIAL AND WILDFIRE 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 PLANNED FOR THIS AWARD.

ACCELERATING DISCOVERY AND DIAGNOSTICS OF PLASMA-WALL INTERACTIONS USING MACHINE LEARNING

UNDERREPRESENTED STUDENTS IN GIFTED & TALENTED EDUCATION: POSITIVE PSYCHOLOGY IDENTIFICATION & SERVICE

TOURETTE SYNDROME GENETICS AND NEUROIMAGING INTERNATIONAL COLLABORATIVE STUDY - TOURETTE SYNDROME (TS) IS CHARACTERIZED BY MULTIPLE, PERSISTENT MOTOR AND VOCAL TICS AND AFFECTS APPROXIMATELY 1% OF CHILDREN WORLDWIDE. THERE IS NO CURE FOR TS AND EFFORTS TO DEVELOP NOVEL TREATMENTS ARE HAMPERED BY OUR LIMITED UNDERSTANDING OF THE UNDERLYING NEUROBIOLOGY AND BRAIN STRUCTURAL AND FUNCTIONAL DEFICITS. ALTHOUGH TICS REPRESENT THE HALLMARK FEATURE OF TS, UP TO 90% OF PATIENTS PRESENT WITH ADDITIONAL NEUROPSYCHIATRIC DISORDERS, INCLUDING OBSESSIVE COMPULSIVE DISORDER (OCD UP TO 50% OF TS PATIENTS), ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD UP TO 54.3%), AUTISM SPECTRUM DISORDERS (ASD UP TO 20%), MAJOR DEPRESSIVE DISORDER (MDD UP TO 26%), AND ANXIETY DISORDERS (AXD UP TO 36%). THESE COMORBIDITIES CONTRIBUTE TO DECREASED QUALITY OF LIFE AND INTRODUCE ETIOLOGICAL AND PHENOTYPIC HETEROGENEITY THAT FURTHER HAMPERS EFFORTS TO ELUCIDATE THE TS NEUROBIOLOGY. HERE, WE ARE PROPOSING TO INVESTIGATE TS-RELATED BRAIN STRUCTURE AND FUNCTION AT A LARGE SCALE BUT ALSO TO IDENTIFY THOSE FACTORS THAT LEAD TO HIGH COMORBIDITY WITH OTHER DISORDERS. MOTIVATED BY INTERNATIONAL COLLABORATIVE STUDIES ON THE GENETICS AND NEUROIMAGING OF TS LED BY THE PI, WE BRING TOGETHER ALL MAJOR WORLDWIDE COLLABORATIVE EFFORTS ON NEUROIMAGING AND GENETICS FOR TS AND AIM TO INTEGRATE WITH EQUIVALENTLY LARGE AND ALREADY EXISTING STUDIES OF HIGHLY COMORBID OCD, ADHD, ASD, MDD, AND AXD. WE TAKE ADVANTAGE OF ACCESS TO DATA, RESOURCES AND STANDARDIZED PIPELINES FROM THE ENIGMA (ENHANCING NEUROIMAGING GENETICS THROUGH META- ANALYSIS) CONSORTIUM AND THE PSYCHIATRIC GENOMICS CONSORTIUM (PGC). FIRST, WE WILL ESTABLISH THE ENIGMA-TS WORKING GROUP, FOR WHICH PI PASCHOU HAS ALREADY LAID THE GROUNDWORK, WITH 17 SITES FROM NINE COUNTRIES HAVING AGREED TO CONTRIBUTE EXISTING NEUROIMAGING AND CLINICAL DATA FROM 1,930 CASES AND CONTROLS. WE WILL POOL TOGETHER T1 STRUCTURAL IMAGING DATA AS WELL AS RSFMRI AND DTI DATA. SECOND, WE WILL PURSUE THE LARGEST NEUROIMAGING STUDIES FOR TS TO DATE AIMING TO UNDERSTAND THE PATHOPHYSIOLOGY OF THE DISORDER. PURSUING CROSS-DISORDER ANALYSIS, WE WILL ALSO INTEGRATE OUR TS NEUROIMAGING DATA WITH EXISTING ENIGMA DATA FOR THE MOST FREQUENTLY COMORBID DISORDERS IN TS (OCD, ADHD, ASD, MDD, AND AXD). THIRD, WE WILL AIM TO UNCOVER BRAIN REGIONS THAT CORRELATE TO GENETIC BACKGROUND IN TS AND RELATED DISORDERS. TO DO THIS WE WILL ANALYZE TS GENOMEWIDE ASSOCIATION STUDIES (GWAS) BUT ALSO PURSUE CROSS-DISORDER GWAS FOR TS AND COMORBID DISORDERS. WE WILL LEVERAGE OUR FINDINGS FROM THE FIRST LARGE-SCALE CROSS-DISORDER GWAS META-ANALYSIS FOR TS, OCD, ADHD, ASD (LED BY THE PI), AS WELL AS ACCESS TO DATA FROM ENIGMA GWAS ON BRAIN STRUCTURE FROM MORE THAN 50,000 INDIVIDUALS AND THE UK BIOBANK ON ADDITIONAL 10,000 INDIVIDUALS. IMPORTANTLY, WE WILL ALSO LEVERAGE ACCESS TO POPULATION-BASED COHORTS (ABCD AND GENERATION R), WITH LONGITUDINAL BRAIN IMAGING, CLINICAL BUT ALSO GENETIC INFORMATION IN ORDER TO REPLICATE OUR FINDINGS TO DIVERSE POPULATIONS AND EXPLORE CORRELATIONS TO BEHAVIOURAL PROFILES MOVING BEYOND STRICT DIAGNOSTIC CATEGORIES. ULTIMATELY, OUR FINDINGS WILL HELP ELUCIDATE BRAIN STRUCTURE AND FUNCTION IN TS BUT ALSO DISENTANGLE RELATIONSHIPS WITH COMORBID OCD, ADHD, ASD, MDD, AND AXD.