Harbor Incorporated

CSHL CANCER CENTER SUPPORT GRANT

COLD SPRING HARBOR LABORATORY CANCER RESEARCH CENTER

A COMPREHENSIVE CENTER FOR MOUSE BRAIN CELL ATLAS

HEALTH CENTER CLUSTER

HEALTH CENTER CLUSTER

DESCRIPTION:THE PURPOSE OF THIS AWARD IS TO PROVIDE FUNDING UNDER THE INFLATION REDUCTION ACT TO OXNARD HARBOR DISTRICT PORT OF HUENEME. SPECIFICALLY, THE RECIPIENT WILL IMPROVE AIR QUALITY AND REDUCE POLLUTION AT THE PORT OF HUENEME AND IN THE SURROUNDING AREA THROUGH THE DEPLOYMENT OF ZERO-EMISSION EQUIPMENT AND INFRASTRUCTURE AT THE PORT. THIS ASSISTANCE AGREEMENT PROVIDES FULL FEDERAL FUNDING IN THE AMOUNT OF $41,076,293.00. PRE-AWARD COSTS APPROVED BACK TO DECEMBER 1, 2024. SEE TERMS AND CONDITIONS. ACTIVITIES:THE ACTIVITIES INCLUDE THE PURCHASE AND DEPLOYMENT OF ELECTRIC CARGO HANDLING EQUIPMENT AND ZERO-EMISSION DRAYAGE TRUCKS, AS WELL AS RELATED ELECTRIC CHARGING INFRASTRUCTURE AND BATTERY ENERGY STORAGE SYSTEMS.SUBRECIPIENT:THE SUBAWARDS WILL ALLOCATE FUNDS TO SSA PACIFIC TO DEPLOY 5 YARD TRACTORSPIECES OF ELECTRIC CARGO HANDLING EQUIPMENT, 2 HEAVY FORKLIFTS, AND 1 SMALL FORKLIFT, AND, TO PORTS AMERICA TO DEPLOY 30 YARD TRACTORS, 1 REACHSTACKER, 2 HEAVY FORKLIFTS, AND 2 SMALL FORKLIFTS. OUTCOMES:THE ANTICIPATED DELIVERABLES INCLUDE THE ESTIMATED PURCHASE AND DEPLOYMENT OF 35 BATTERY ELECTRIC YARD TRACTORS, 4 BATTERY ELECTRIC HEAVY LIFTS, AND 1 BATTERY ELECTRIC REACHSTACKER; DEPLOYMENT OF 44 ELECTRIC CHARGING UNITS AND BATTERY ENERGY STORAGE SYSTEMS; AND ESTABLISHING AN INCENTIVE PROGRAM TO ACCELERATE THE TRANSITION TO ZERO-EMISSION DRAYAGE TRUCKS. OTHER DELIVERABLES INCLUDE COMMUNITY TRAINING ON AIR QUALITY AND ZERO-EMISSION EQUIPMENT AND CONDUCTING LOCAL JOB FAIRS AND INTERNSHIP PROGRAMS. THE EXPECTED OUTCOMES INCLUDE REDUCED NOX, PM2.5, AND CO2 EMISSIONS; REDUCED RELIANCE ON DIESEL FUEL; IMPROVED AIR QUALITY AND ASSOCIATED HEALTH BENEFITS; INCREASED RESILIENCY AGAINST POWER OUTAGES; IMPROVED UNDERSTANDING OF AIR QUALITY ISSUES AND ZERO EMISSIONS IN THE LOCAL COMMUNITY; AND INCREASED ACCESS TO HIGH-QUALITY JOB OPPORTUNITIES FOR NEAR-PORT COMMUNITIES. THE INTENDED BENEFICIARIES INCLUDE THE PORT OF HUENEME (GRANTEE), SSA PACIFIC (PARTNER), PORTS AMERICA (PARTNER) SOUTHERN CALIFORNIA EDISON (PARTNER), AND VENTURA COUNTY AIR POLLUTION CONTROL DISTRICT(PARTNER), WHO WILL DEPLOY AND UTILIZE THE ZERO-EMISSION EQUIPMENT AND CHARGING INFRASTRUCTURE. OTHER BENEFICIARIES INCLUDE VENTURA COUNTY COMMUNITY COLLEGE DISTRICT (PARTNER), OXNARD UNIFIED HIGH SCHOOL DISTRICT (PARTNER), AND RIO SCHOOL DISTRICT (PARTNER), WHO WILL IMPLEMENT COMMUNITY ENGAGEMENT EFFORTS. INDIRECT BENEFICIARIES INCLUDE NEAR-PORT COMMUNITIES WHICH WILL EXPERIENCE IMPROVED AMBIENT AIR QUALITY.

PORT SECURITY GRANT PROGRAM

AWARD PURPOSE THE PROJECT WILL FUND IMPROVEMENTS TO TERMINAL 4 AT THE PORT OF GRAYS HARBOR. ACTIVITIES TO BE PERFORMED THE PROJECT INCLUDES THE CONSTRUCTION OF APPROXIMATELY 40000 FEET OF ADDITIONAL RAIL TO ACCOMMODATE UNIT TRAINS AND RAILCAR STORAGE THE REPURPOSING OF A 50 ACRE BROWNFIELD SITE INTO A BREAKBULK CARGO HANDLING AND LAYDOWN AREA ACCESS AND ROADWAY IMPROVEMENTS REPLACEMENT OF MARINE TERMINAL FENDERING SYSTEMS AND RELATED SITE IMPROVEMENTS. DELIVERABLES EXPECTED OUTCOMES THE PROJECT WILL IMPROVE CARGO FLOW INTO AND THROUGH THE INTERNATIONAL SHIPPING COMPLEX. INTENDED BENEFICIARY PORT OF GRAYS HARBOR. SUBRECIPIENT ACTIVITIES NA.

THE NEW BEDFORD HARBOR DEVELOPMENT COMMISSION (NBHDC) WILL SUPPORT EPA IN THE DESIGN AND CONSTRUCTION OF A CONFINED AQUATIC DISPOSAL (CAD) CELL IN NE

FY 2011 PORT SECURITY GRANT PROGRAM

AWARD PURPOSE THE PROJECT WILL FUND TWO REACH STACKERS. THE REACH STACKERS WILL BE USED AS THE PRIMARY EQUIPMENT FOR CARGO MOVEMENTS ASSOCIATED WITH THE PORT OF BEAUMONT CONTAINER ON BARGE SERVICE OPERATING BETWEEN THE PORTS OF BEAUMONT AND HOUSTON. ACTIVITIES TO BE PERFORMED THE PROJECT FUNDS THE PROCUREMENT OF TWO BUY AMERICA-COMPLIANT REACH STACKERS THAT WILL BE USED AS THE PRIMARY EQUIPMENT FOR CARGO MOVEMENTS ASSOCIATED WITH THE PORT OF BEAUMONT CONTAINER ON BARGE SERVICE COBS FROM THE PORT OF BEAUMONT TO PORT HOUSTON. REACH STACKER 1 WILL BE USED TO LOAD CONTAINERS TO BARGE FROM THE PORT OF BEAUMONTS BARGE DOCK. THIS PIECE OF EQUIPMENT REQUIRES A NEGATIVE REACH TO EXTEND FROM LAND INTO THE BARGE WHICH WILL BE BELOW GRADE. THE EQUIPMENT IS NOT FULLY AUTOMATED. REACH STACKER 2 WILL BE USED IN THE CONTAINER MARSHALLING YARD FOR THE LOADING AND UNLOADING OF CONTAINERS TO TRUCK AND OR RAIL. THIS EQUIPMENT WILL OPERATE AT-GRADE AND WILL NOT REQUIRE A NEGATIVE REACH. THE EQUIPMENT IS NOT FULLY AUTOMATED. DELIVERABLES EXPECTED OUTCOMES FROM SCHEDULE G OF THE GRANT AGREEMENT PAGE 10 QUANTITY OF FREIGHT BEING MOVED TEUS METRIC TONS OR CUBIC BOARD METER CBM - PROVIDE THE UNIT OF MEASURE OF FREIGHT MOVED BY THE SERVICE. QUARTERLY. CARGO LIFTS - PROVIDE THE NUMBER OF CARGO LIFTS PERFORMED IN THE PROJECT STUDY AREA. QUARTERLY. HIGHWAY VEHICLE MILES TRAVELED VMT - COMMERCIAL VEHICLE MILES TRAVELED VMT IS CALCULATED BY OBTAINING THE ROAD MILES TRAVELED ON THE DESIGNATED MARINE HIGHWAY ROUTE. QUARTERLY. FUEL SAVINGS GREENHOUSE GAS EMISSIONS - CALCULATE THE AMOUNT OF FUEL IN GALLONS SAVED. QUARTERLY. CO2 EMISSIONS REDUCED GREENHOUSE GAS EMISSIONS. PROVIDE THE AMOUNT OF CO2 THE SERVICE WILL REDUCE. QUARTERLY. MAINTENANCE SAVINGS PER MILE GREENHOUSE GAS EMISSIONS. PROVIDE THE CONGESTION SAVINGS BY THE SERVICE. QUARTERLY. CONGESTION MITIGATION SAVINGS PER MILE. PROVIDE THE MAINTENANCE SAVINGS. QUARTERLY. INTENDED BENEFICIARY PORT OF BEAUMONT NAVIGATION DISTRICT OF JEFFERSON CO. SUBRECIPIENT ACTIVITIES NONE.

GENERAL CLINICAL RESEARCH CENTER

HEALTH CENTER CLUSTER

APPLICATION PURPOSE: THE PURPOSE OF THIS AWARD IS TO PROVIDE FUNDING FOR THE CONSTRUCTION OF A NEW OPERATIONS CENTER DURING THE PERIOD OF 01/01/2025-3/30/2028 WITH A PROPANE FUELING STATION AND VEHICLE REPLACEMENT.; ACTIVITIES PERFORMED: FUNDS WILL BE USED TO COVER ALL ELIGIBLE CONSTRUCTION ACTIVITIES SUCH AS SITEWORK FOUNDATION ROUGH FRAMING EXTERIOR CONSTRUCTION MECHANICAL ELECTRICAL PLUMBING FIBER AND FIXTURES. PROCURING PROPANE VEHICLES AND A FUELING STATION.; EXPECTED OUTCOMES: EXPANDED HOURS CLEAN AIR REDUCED CONGESTION AND IMPROVE EFFICIENCY.; INTENDED BENEFICIARIES: RIDERS EMPLOYEES AND COMMUNITIES THE AGENCY SERVICES WILL RECEIVE THE BENEFIT OF THIS AWARD.; SUBRECIPIENT ACTIVITIES: NONE

FY 2023 DISASTER GRANT-WATER ONLY

AWARD PURPOSE THE PROJECT CONSISTS OF TWO ELEMENTS 1 EXPANDED INTERMODAL RAIL CAPACITY AND 2 CARGO GATE OPTIMIZATION. THE RAIL CAPACITY COMPONENT WILL CONSTRUCT TWO NEW RAIL TRACKS APPROXIMATELY 3200 FEET LONG WITH ACCESS RAIL ACQUIRE THREE NEW ELECTRIC RUBBER TIRED GANTRY CRANES RECONSTRUCTS APRON AREAS ON ALL SIDES OF THE TRACK INSTALLS LED LIGHTS AND RECONSTRUCTS THE STORMWATER DRAINAGE SYSTEM TO ADDRESS SEA LEVEL RISE. THE CARGO GATE OPTIMIZATION PROJECT WILL INCLUDE ROADWAY REALIGNMENTS TO AND FROM CARGO GATES REHABILITATION OF THE STORMWATER MANAGEMENT SYSTEM TO ADDRESS SEA LEVEL RISE CARGO GATE CANOPIES STAGING AREAS FOR TRUCKS DIRECT ACCESS TO RAIL YARD GATES RELOCATION OF CARGO GATE SUPPORT AND TERMINAL OFFICES AND TECHNOLOGY INCLUDING RFID READERS OCR OPTICAL CHARACTER RECOGNITION WIM SCALES REMOTE INSPECTION EQUIPMENT GATE MANAGEMENT SYSTEM. ACTIVITIES TO BE PERFORMED THIS PROJECT WILL FUND THREE COMPONENTS AT PORTMIAMI DESIGN CRITERIA PACKAGE EXPANDED INTERMODAL RAIL CAPACITY AND CARGO GATE OPTIMIZATION. COMPONENT 1 INITIAL DESIGN CRITERIA PACKAGE THE DESIGN CRITERIA DOCUMENTS FOR THE EXPANDED INTERMODAL RAIL CAPACITY PROJECT CONSISTS OF THE FOLLOWING SUBMITTALS PRELIMINARY PROGRAM AND REFINED CONCEPTUAL DESIGN AND ROUGH ORDER OF MAGNITUDE CONSTRUCTION COST ESTIMATES. DESIGN CRITERIA PACKAGE WITH DETAILED PARAMETERS AND NARRATIVES INCLUDING TRACK CONCEPTUAL LAYOUT AND FOOTPRINT SUSTAINABLE DESIGN REQUIREMENTS UTILITIES GANTRY CRANE HURRICANE TIE DOWNS TRUCK TURNING ANALYSIS ETC FOR A DESIGN BUILD CONTRACTOR TO SUCCESSFULLY BUILD THE PROJECT. TECHNICAL SPECIFICATIONS FOR THE ELECTRIC RAIL GANTRY CRANES TO ALIGN WITH THE EXPANDED INTERMODAL RAIL DESIGN. COMPONENT 2 DESIGN BUILD EXPANDED INTERMODAL RAIL CAPACITY. CONSTRUCTION OF THE ACCESS RAIL TRACK TWO NEW TRACKS APPROXIMATELY 3200 FEET LONG EACH AND INSTALLATION OF A RAILROAD SWITCH TO THE TRACKS WITHIN THE INTERMODAL RAIL YARD. REMOVAL AND REPLACEMENT OF EXISTING PAVEMENT. RECONSTRUCTION OF APRON AREA INCLUDING FILLING AND GRADING TO CREATE A STABLE BASE FOR THE TRAIN TRACKS AND APRON. RECONSTRUCTION OF STORMWATER DRAINAGE STRUCTURES AND PLACEMENT OF ASPHALT PAVING IN THE APRON AREA. INSTALLATION OF ADDITIONAL LED LIGHTS AS REQUIRED FOR SECURITY PURPOSES. ADDITIONAL CARGO HANDLING EQUIPMENT INCLUDING THREE 3 BUY AMERICA COMPLIANT NEW ELECTRIC RUBBER TIRED GANTRY CRANES E RTG TO BE ACQUIRED BY PORTMIAMI TO LOAD AND UNLOAD THE CONTAINERS FROM THE TRAINS. COMPONENT 3 DESIGN BUILD CARGO GATE OPTIMIZATION THE OPTIMIZATION OF THE CARGO GATES WILL RELOCATE AND MODERNIZE THE CARGO GATE SYSTEM FOR ONE OF PORTMIAMIS PRIMARY CONTAINER TERMINALS AND INCLUDES THE FOLLOWING ELEMENTS ROADWAY REALIGNMENTS TO AND FROM CARGO GATES. THIS INCLUDES THE IMPROVEMENTS SUCH AS PAVING FENCING AND STRIPING ON THE ROAD LEADING TO AND FROM THE RELOCATED GATES. REHABILITATION OF THE STORMWATER MANAGEMENT SYSTEM TO ADDRESS SEA LEVEL RISE HIGH TIDES STORM EVENTS AND TO MINIMIZE FLOODING. NEW CARGO GATE CANOPIES AS REQUIRED ALONG BOTH THE INBOUND AND OUTBOUND SECURITY GATES. NEW STAGING AREAS FOR TRUCKS IN THE PROBLEM RESOLUTION AREA. DIRECT ACCESS TO INTERMODAL RAIL YARD SECURITY GATES. RELOCATION OF CARGO GATE SUPPORT AND TERMINAL OFFICES TO ACCOMMODATE THE NEW CARGO GATE SYSTEM. GATE MODERNIZATION TO INCLUDE RFID READERS OCR WIM SCALES REMOTE INSPECTION EQUIPMENT AND INNOVATIVE TECHNOLOGY FOR THE GATE MANAGEMENT SYSTEM. DELIVERABLES EXPECTED OUTCOMES PERFORMANCE MEASURE TABLE FROM SCHEDULE G PAGE 10 OF THE GRANT AGREEMENT GROSS TONS OR TEUS ECONOMIC COMPETITIVENESS THE MOVEMENT OF GROSS TONNAGE OR TWENTY FOOT EQUIVALENT UNIT TEU OF FREIGHT IN THE AREA DEFINED BY THE PROJECT STUDY AREA SECONDARY VARIABLE TYPE OF INTERMODAL TRANSPORT RAIL OR TRUCK QUARTERLY. AVERAGE DAILY TRUCK TRAFFIC ADTT ECONOMIC COMPETITIVENESSADTT MEASURES THE TOTAL VOLUME OF CARGO AT THE PORT FOR THE INTERMODAL RAIL YARD AND THE CARGO YARD AND DIVIDES BY THE NUMBER OF DAYS PER QUARTER. QUARTERLY. INTENDED BENEFICIARY MIAMI DADE COUNTY. SUBRECIPIENT ACTIVITIES NONE.

AWARD PURPOSE THROUGH THIS PROJECT THE NEW BEDFORD HARBOR DEVELOPMENT COMMISSION WILL DESIGN AND BUILD A NORTH SOUTH BULKHEAD AT THE NORTH TERMINAL IN NEW BEDFORDS UPPER HARBOR. THE NEW BULKHEAD WILL BE BACKFILLED WITH GEOTECHNICALLY SUITABLE CLEAN SEDIMENT AS OBTAINED THROUGH THE CONSTRUCTION OF A CONFINED AQUATIC DISPOSAL CAD CELL SUPPORTING NAVIGATIONAL HARBOR DREDGING. THE PROJECT INCLUDES ONE MAJOR PROCUREMENT FOR A CONTRACTOR THAT WILL A BUILD THE NORTH TERMINAL BULKHEAD, B BACKFILL THE BULKHEAD WITH CLEAN MATERIAL, AND C PURCHASE AMERICAN-MADE STEEL TO BUILD THEBULKHEAD. ACTIVITIES TO BE PERFORMED THE NORTH TERMINAL EXTENSION PROJECT CONSISTS OF CREATING A NEW BULKHEAD AND TERMINAL, BACKFILLING THE BULKHEAD WITH GEOTECHNICALLY SUITABLE MATERIAL SOURCED FROM A NEW CONFINED AQUATIC DISPOSAL CAD CELL, THE CAD CELL CONSTRUCTION AND PHASE V DREDGING. NORTH TERMINAL BULKHEAD THIS PROJECT INCLUDES DESIGN AND CONSTRUCTION OF AN ESTIMATED ADDITIONAL 975 LINEAR FEET OF BULKHEAD, COMPRISED OF CELLULAR COFFERDAMS. THE BULKHEAD WILL EXTEND FROM THE EXISTING ENVIRONMENTAL PROTECTION AGENCY BUILDING SITE AND CONTINUE NORTH TO ADJOIN AN EXISTING BULKHEAD THAT IS LOCATED NORTH OF THE AREA. COMPONENT 2 BACKFILL AND TERMINAL BACKFILL THE NEWLY CONSTRUCTED BULKHEAD WILL BE BACKFILLED WITH APPROXIMATELY 200 000 CUBIC YARDS OF CLEAN SUITABLE MATERIAL SOURCED FROM THE CAD CELL AND AN ESTIMATED 75000 CUBIC YARDS OF IMPORTED STRUCTURAL FILL WILL BE USED FOR THE CELLULAR COFFERDAMS TERMINAL APPROXIMATELY 350,000 SQUARE FEET OF UPLAND TERMINAL SPACE WILL BE CREATED THROUGH THE AREA BACKFILLED LANDWARD OF THE BULKHEAD. THE TERMINAL AREA WILL BE FILLED WITH A FINISH LAYER OF DENSE GRADED AGGREGATE. COMPONENT 3 CAD CELL CONSTRUCTION AND PHASE V DREDGING CAD CELL CONSTRUCTION THE PROJECT CONSISTS OF CREATING A CAD CELL WITHIN THE HARBOR THAT WILL HAVE THECAPACITY TO HOLD APPROXIMATELY 450 000 TO 500 000 CUBIC YARDS OVER AN AREA OF 620 000 SQUARE FEET. THE DESIGN FOR THE CAD CELL HAS BEEN PREVIOUSLY COMPLETED. THE FIRST LAYER OF APPROXIMATELY 30000 CUBIC YARDS OF DREDGED MATERIAL WILL BE DISPOSED IN AN EXISTING CAD CELL LOCATED IN THE HARBOR THE SUBSEQUENT LAYER OF APPROXIMATELY 300 000 TO 320 000 CUBIC YARDS WILL BE DISPOSED AT AN OFFSHORE DISPOSAL SITE AND THE FINAL LAYER OF APPROXIMATELY 200 000 CUBIC YARDS WILL BE USED AS BACKFILL FOR THE NORTH TERMINAL BULKHEAD. PHASE V DREDGING THE PROJECT CONSISTS OF DREDGING APPROXIMATELY 70000 CUBIC YARDS OF CONTAMINATED MATERIAL LOCATED IN FRONT OF THE NORTH TERMINAL AND APPROXIMATELY 380000 TO 430000 CUBIC YARDS OF CONTAMINATED SEDIMENT FROM THE HARBOR. THESE MATERIALS WILL BE PLACED INTO THE CAD CELL. DELIVERABLES EXPECTED OUTCOMES SEE FROM PAGES 21 AND 22, ATTACHMENT D OF THE GRANT AGREEMENT: INTENDED BENEFICIARY CITY OF NEW BEDFORD SUBRECIPIENT ACTIVITIES NONE

RECONSTRUCTION OF THE CHALMETTE SHIP

PORT OF HUENEME INTERMODAL INFRASTRUCTIURE PROJECT

HEERF EMERGENCY FUNDINGFUNDING TO SUPPORT EMERGENCY EXPENSES RELATED TO COVID-19 PANDEMIC

COMPREHENSIVE CHARACTERIZATION AND CLASSIFICATION OF THE HUMAN TRANSCRIPTOME

COLLABORATORY FOR ATLASING CELL TYPE ANATOMY IN THE FEMALE AND MALE MOUSE BRAIN

INITIATION OF DNA REPLICATION AT CELL ORIGINS IN YEAST

IPGA: GRAMENE - EXPLORING FUNCTION THROUGH COMPARATIVE GENOMICS AND NETWORK ANALYSIS

PROTEIN TYROSINE DEPHOSPHORYLATION & SIGNAL TRANSDUCTION

HEALTH CENTER CLUSTER

COMPETITIVE COOPERATIVE AGREEMENT: U.S. INDUSTRY OPPORTUNITIES FOR ADVANCED NUCLEAR TECHNOLOGY DEVELOPMENT FOA #DE-FOA-0001817

LANDSCAPE OF TRANSCRIPTION IN HUMAN AND MOUSE

SYSTEMS IMMUNOLOBIOLOGY OF ANTIBIOTIC-PERSISTENT MRSA INFECTION

AWARD PURPOSE THE PROJECT FUNDS THE EXPANSION OF THE PORT OF MORGAN CITYS DOCK BY ADDING APPROXIMATELY 1 6 ACRES OF CONCRETE LAYDOWN AREA AND BUILDING AN ADDITIONAL 8880 SQUARE FOOT WHARF RELIEVING PLATFORM STRUCTURE TO SUPPORT A 440 BY 40 WHARF EXTENSION. THE PROJECT COMPLEMENTS PHASE 3A THAT WAS FUNDED BY THE PORT AND THE STATE OF LOUISIANA AND COMPLETES ALL PHASES OF THE PORTS WESTERN DOCK EXPANSION PROJECT. ACTIVITIES TO BE PERFORMED THE PROJECT INCLUDES TWO COMPONENTS COMPONENT 1 CONSTRUCT AN APPROXIMATELY 8880 SQUARE FOOT WHARF RELIEVING PLATFORM STRUCTURE TO SUPPORT AN APPROXIMATELY 440 BY 40 WHARF EXTENSION. THE PROPOSED WHARF EXTENSION WILL BE SUPPORTED BY PRECAST CONCRETE PILES AND PRECAST CONCRETE CAPSILLS. THE WHARF DECK WILL BE CONSTRUCTED WITH STEEL REBARRE INFORCED CAST IN PLACE STRUCTURAL CONCRETE. COMPONENT 2 CONSTRUCT APPROXIMATELY 1 6 ACRES OF CONCRETE PAVED CARGO LAYDOWN AREA AND ASSOCIATED SITE INFRASTRUCTURE SUCH AS SUBSURFACE GRAVITY DRAINAGE AND UTILITIES. THE EXISTING GROUND BELOW THE LAYDOWN AREA WILL REQUIRE SOIL IMPROVEMENTS CONSISTING OF A DEEP SOIL MIXING PROGRAM BELOW THE ENTIRE LAYDOWN AREA FOOTPRINT. SUBSURFACE GRAVITY DRAINAGE IS TO BE INSTALLED JUST NORTH OF THE PROPOSED BULKHEAD TO DRAIN THE PAVED AREAS AS WELL AS BETWEEN THE EXISTING FEDERAL FLOOD PROTECTION AND EDGE OF THE LAYDOWN AREA. THE GRAVITY DRAINAGE SYSTEM WILL CONSIST OF PRECAST CONCRETE DRAINPIPE AND PRECAST CONCRETE CATCH BASINS. PUMP STATION OUTFALL PIPES WILL BE EXTENDED THROUGH THE PROPOSED BULKHEAD TO DISCHARGE INTO BAYOU BOEUF. UTILITIES. DELIVERABLES EXPECTED OUTCOMES PERFORMANCE MEASURE TABLE FROM SCHEDULE G PAGE 03 OF THE GRANT AGREEMENT MEASURE VESSEL CALLS. CATEGORY AND DESCRIPTION VESSEL TYPE AND OR FREIGHT CAPACITY OF THE VESSELS CALLING TO THE AREA DEFINED IN THE PROJECT STUDY AREA. MEASUREMENT FREQUENCY QUARTERLY. MEASURE GROSS TONS. CATEGORY AND DESCRIPTION THE MOVEMENT OF GROSS TONNAGE OF FREIGHT, IN THE AREA DEFINED BY THE PROJECT STUDY AREA. SECONDARY VARIABLES TYPES OF FREIGHT TYPES OF INTERMODAL TRANSPORT. MEASUREMENT FREQUENCY QUARTERLY. INTENDED BENEFICIARY MORGAN CITY HARBOR AND TERMINAL DISTRICT. SUBRECIPIENT ACTIVITIES NONE.

BTI INFRASTRUCTURE EXPANSION PROJECT

THIS PROJECT PLANS TO CONSTRUCT A RUN-OF-THE-RIVER HYDROELECTRIC FACILITY WITH A DIVERSION STRUCTURE, PIPELINE, POWERHOUSE, AND ELECTRIC TRANSMISSION LINE IN OLD HARBOR, ALASKA. IT IS ANTICIPATED THAT THE PROJECT WILL BE CAPABLE OF GENERATING ABOUT 3,470 MWH OF ENERGY ANNUALLY AND OFFSET DIESEL FUEL USE AT THE LOCAL POWER PLANT BY 95%, ENABLING A YEAR-ROUND RELIABLE ENERGY SOURCE. OLD HARBOR IS A REMOTE ALUTIIQ TRIBAL VILLAGE ON KODIAK ISLAND, ALASKA, APPROXIMATELY 50 AIR MILES FROM THE NEAREST SOCIAL SERVICES IN THE CITY OF KODIAK. THERE ARE NEARLY 200 RESIDENTS IN OLD HARBOR AND 83% ARE NATIVE ALASKANS WHO RELY ON A SUBSISTENCE DIET, COLLECTING BERRIES, FISH, AND GAME MEAT FOR FOOD. ACCORDING TO THE DENALI COMMISSION, 88% OF RESIDENTS LIVE BELOW THE FEDERAL POVERTY LINE, WITH A MEDIAN HOUSEHOLD INCOME OF $13,181, AND EXPERIENCE DISPROPORTIONALLY HIGHER COST ENERGY BILLS. AS PART OF ITS COMMUNITY BENEFITS PLAN, THE ALUTIIQ TRIBE AND PROJECT PARTNERS WILL WORK TO ENSURE STABLE SOURCES OF CLEAN WATER AND ENERGY WHILE REDUCING THE NEGATIVE HEALTH IMPACTS OF USING DIESEL FUEL. THE TRIBE INTENDS TO SELL HYDROPOWER GENERATED THROUGH THE PROJECT TO LOCAL UTILITIES FOR 80% OF THE AVOIDED COST OF A GALLON OF DIESEL FUEL. THE PROJECT WILL ENSURE ENERGY SECURITY AND WILL PROVIDE BENEFITS TO EACH HOUSEHOLD. THE OLD HARBOR HYDROELECTRIC PROJECT SEEKS TO DEMONSTRATE A TRIBAL OWNERSHIP BUSINESS MODEL THAT MAY BE REPLICABLE IN 209 SIMILAR RURAL VILLAGES WITHIN THE REGION.

CONSTRUCTION - CHRONIC DISEASE CLINICAL RESEARCH CENTER

HEALTH CENTER PROGRAM

STRUCTURE AND FUNCTION OF NMDA RECEPTORS

WASTE DISPOSAL GRANTS - REGULAR

AWARD PURPOSE THIS PROJECT INCLUDES STUDIES SITE DESIGN AND ENGINEERING SITE INVESTIGATIONS AND PERMITING ACTIVITIES FOR A HEAVY LIFT MARINE TERMINAL FACILITY AT THE REDWOOD MARINE TERMINAL RMT TO SUPPORT OFFSHORE WIND FARM DEVELOPMENT. THE PROJECT ALSO INCLUDES CREATION OF A BAYWIDE MASTER PLAN PROJECT MANAGEMENT AND GRANT ADMINISTRATION. ACTIVITIES TO BE PERFORMED THE OBJECTIVES OF THE RMT HEAVY LIFT WIND TERMINAL ELEMENTS OF THE PROJECT ARE TO COMPLETE ALL REMAINING REQUIRED SPECIAL STUDIES AND DATA COLLECTION EFFORTS ADVANCE THE ALREADY IN PROGRESS DESIGN ENGINEERING FROM 10 PERCENT TO GREATER THAN 30 PERCENT COMPLETE CALIFORNIA ENVIRONMENTAL QUALITY ACT CEQA AND NATIONAL ENVIRONMENTAL POLICY ACT NEPA DOCUMENTATION AND PERMITTING AND COMPLETE FINAL DESIGN FOR THE SITES ACCESS ROADS AND REQUIRED HABITAT MITIGATION. THE PURPOSE OF THE BAYWIDE MASTER PLAN ELEMENT OF THE PROJECT IS TO LOOK BEYOND THE RMT SITE IDENTIFY OTHER POTENTIAL OFFSHORE WIND ENERGY RELATED PROJECTS WITHIN HUMBOLDT BAY AND DETERMINE OTHER WEST COAST AND REGIONAL NEEDS THAT HUMBOLDT BAY CAN SATISFY.

HEERF EMERGENCY FUNDING FUNDING TO SUPPORT STUDENT EMERGENCY EXPENSES RELATED TO COVID-19 PANDEMIC

SPATIAL ORGANIZATION OF GENE EXPRESSOIN

AWARD PURPOSE THE PROJECT WILL REBUILD THE EXISTING DOCK STRUCTURE TO BETTER WITHSTAND OPERATIONAL AND WEATHER HAZARDS WIDEN THE DOCKS TO ALLOW A GREATER NUMBER OF TRUCKS THROUGH AND INSTALL HOISTS TO LOAD/UNLOAD CARGO MORE EFFICIENTLY. ACTIVITIES TO BE PERFORMED COMPONENT 1 GRANT ADMINISTRATION MEETINGS WITH USDOT AND OTHER FEDERAL STATE AND LOCAL AGENCIES AND COMMUNITY STAKEHOLDERS TO ENSURE PROJECT PROCESS MEETS ALL APPLICABLE FEDERAL REQUIREMENTS. HOLD PUBLIC INVOLVEMENT MEETINGS WHICH WILL CONTINUE THROUGHOUT THE PROJECT. PREPARE FINAL CONSTRUCTION BID PACKAGES. RELEASE AND ADVERTISE THE CONSTRUCTION BID PACKAGE. PROJECT AND BID CONSTRUCTION AVAILABILITY. REVIEW BID RESPONSES FOR INCLUSION OF ALL REQUIRED SUBMISSION DOCUMENTS AND REQUIREMENTS. REVIEW BID RESPONSES TO ENSURE THEY COMPLY WITH APPLICABLE FEDERAL REQUIREMENTS. REVIEW PAST PERFORMANCE OF BID RESPONDERS AND MEET WITH RESPONDERS TO ANSWER TECHNICAL QUESTIONS BID ITEMS ETC. HOLD PUBLIC MEETING AND FACILITATE THE AWARD OF CONTRACTS. FINALIZE AND SIGN ALL PROJECT PARTNERSHIP AND IMPLEMENTATION AGREEMENTS. ADMINISTRATION OF THE PROJECT DURING THE CONSTRUCTION PHASE AND CLOSEOUT. COMPONENT 2 ENGINEERING DESIGN AND PERMITTING COMPLETE FINAL TECHNICAL AND ENGINEERING DESIGN OF THE PROJECT. FINALIZE PROJECT COSTS. SECURE ALL STATE AND LOCAL APPROVALS AND CONSTRUCTION PERMITS. COMPLETE ALL REQUIREMENTS FOR FEDERAL NEPA REVIEW. COMPONENT 3 CONSTRUCTION PHASE CONSTRUCT A NEW APPROXIMATELY 13760 SQ FT CONCRETE DECKED DOCK THAT WILL WITHSTAND 50 YEAR TSUNAMI EVENT TIDAL SURGES AND OTHER NATURAL HAZARDS. ENSURE ALL MATERIALS MEET DOMESTIC PREFERENCE REQUIREMENTS. INSTALL ELECTRICAL SEWER WATER AND MECHANICAL INFRASTRUCTURE TO SERVE BUSINESSES ON THE DOCK. INSTALL 12 NEW AND REFURBISHED HOISTS TO IMPROVE MOVEMENT OF GOODS IN THE PORT. DELIVERABLES EXPECTED OUTCOMES FROM PAGE 12 OF THE GRANT AGREEMENT SCHEDULE G MEASURE VESSEL CALLS. CATEGORY AND DESCRIPTION MEASUREMENT FREQUENCY QUARTERLY. MEASURE CARGO DWELL TIME. CATEGORY AND DESCRIPTION ECONOMIC COMPETITIVENESS AND OPPORTUNITY THE NUMBER OF VESSELS CALLING TO THE AREA DEFINED IN THE PROJECT STUDY AREA. MUST BE REPORTED IN TOTAL AND DISAGGREGATED BY ANY OF THE FOLLOWING WHERE APPLICABLE VESSEL TYPE EG CONTAINER BULK RO RO LNG FREIGHT CAPACITY VESSEL LENGTH OR OTHER. MEASUREMENT FREQUENCY QUARTERLY. MEASURE CLOSURE FROM NATURAL HAZARDS. CATEGORY AND DESCRIPTION ECONOMIC COMPETITIVENESS AND OPPORTUNITY MOBILITY AND COMMUNITY CONNECTIVITY AVERAGE CARGO DWELL TIME HOURS PER TON OR TEU. DWELL TIME IS DEFINED AS THE TIME BETWEEN CARGO ARRIVAL AND DEPARTURE BY VESSEL TRUC OR RAIL. MEASUREMENT FREQUENCY QUARTERLY. INTENDED BENEFICIARY CRESCENT CITY HARBOR DISTRICT. SUBRECIPIENT ACTIVITIES NONE.

BIOCHEMISTRY OF PRE-MRNA SPLICING

WASTE DISPOSAL GRANTS - REGULAR

AWARD PURPOSE THE PROJECT INCLUDES THE CONSTRUCTION OF A NEW SEAWALL THE REPAIR AND RENOVATION OF A SEAFOOD PACKING AND TRUCK LOADING AREA THE REPLACEMENT OF CARGO HANDLING EQUIPMENT THAT IS CURRENTLY ATOP THE EXISTING SEAWALL AND THE INSTALLATION OF ELECTRICAL INFRASTRUCTURE TO POWER THE COLD STORAGE TRAILERS USED TO MOVE SEAFOOD PRODUCTS TO MARKET. ACTIVITIES TO BE PERFORMED THIS PROJECT WILL FUND CONSTRUCTION OF A NEW SEAWALL TO PROTECT CITIZENS DOCK ROAD REPAIR AND RENOVATE THE SEAFOOD PACKING AND TRUCKING AREA DAMAGED BY SEAWATER INFLOW AND REPLACE THE AGED CARGO HANDLING EQUIPMENT ATOP THE SEAWALL TO IMPROVE THE SAFETY EFFICIENCY AND RELIABILITY OF LOADING AND UNLOADING OF GOODS AT THE PORT AND IMPROVE PORT RESILIENCE. THE PROJECT CONSISTS OF THREE COMPONENTS COMPONENT 1 GRANT ADMINISTRATION MEETINGS WITH USDOT AND OTHER FEDERAL STATE AND LOCAL AGENCIES AND COMMUNITY STAKEHOLDERS TO ENSURE PROJECT PROCESS MEETS ALL APPLICABLE FEDERAL REQUIREMENTS AND MEETS ALL FEDERAL TRANSPORTATION REQUIREMENTS. HOLD PUBLIC INVOLVEMENT MEETINGS THROUGHOUT THE PROJECT. PREPARE FINAL CONSTRUCTION BID PACKAGES. RELEASE THE CONSTRUCTION BID PACKAGE AND ADVERTISE. PROJECT AND BID CONSTRUCTION AVAILABILITY. RECEIVE BID RESPONSES. REVIEW BID RESPONSES FOR INCLUSION OF ALL REQUIRED SUBMISSION DOCUMENTS AND REQUIREMENTS. REVIEW BID RESPONSES TO ENSURE THEY COMPLY WITH APPLICABLE FEDERAL REQUIREMENTS. REVIEW PAST PERFORMANCE OF BID RESPONDERS AND MEET WITH RESPONDERS TO ANSWER TECHNICAL QUESTIONS BID ITEMS ETC. HOLD PUBLIC MEETING AND AWARD BIDS. FINALIZE AND SIGN ALL PROJECT PARTNERSHIP AND IMPLEMENTATION AGREEMENTS. ADMINISTER THE PROJECT DURING THE CONSTRUCTION PHASE AND CLOSEOUT. COMPONENT 2 ENGINEERING DESIGN AND PERMITTING COMPLETE FINAL TECHNICAL AND ENGINEERING DESIGN OF THE PROJECT. FINALIZE PROJECT COSTS. SECURE ALL STATE AND LOCAL APPROVALS AND CONSTRUCTION PERMITS. COMPLETE ALL REQUIREMENTS FOR FEDERAL NEPA REVIEW. COMPONENT 3 SEAWALL CONSTRUCTION AND SEAFOOD PACKING AREA RENOVATION. RECONSTRUCTION AND ELEVATION OF THE SEAWALL WITH A STRUCTURE THAT WILL WITHSTAND 50 YEAR TSUNAMI EVENT TIDAL SURGES AND OTHER CLIMATE RELATED NATURAL HAZARDS TO INCLUDE THE FOLLOWING ELEMENTS DEMOLITION OF THE EXISTING SEAWALL. DEMOLITION OF THE EXISTING RUSTED HOIST THAT IS ATOP THE CURRENT SEAWALL. REMOVE THE ASPHALT CEMENT PARKING LAYER OF THE LAND BEHIND THE SEAWALL. REFILL THE AREA BY REPLACING THE DIRT ROCKSAND FILL THAT HAVE WASHED OUT. APPLY NEW ASPHALT TO THAT AREA AND SEAL THE ASPHALT. FURNISH AND INSTALL BOLLARDS FENDERS AND RELATED UTILITIES. REPAIR RENOVATE SEAFOOD PACKING TRUCKING AREA TO INCLUDE THE FOLLOWING ELEMENTS. REDESIGN THE TRUCK PARKING AND SEAFOOD PACKING AREA TO INCREASE THE NUMBER OF TRUCKS THE AREA CAN HOLD. INSTALL ELECTRICAL INFRASTRUCTURE TO POWER THE COLD STORAGE TRAILERS. INSTALL TWO NEW HOISTS TO IMPROVE MOVEMENT OF GOODS IN THE PORT. DELIVERABLES EXPECTED OUTCOMES PERFORMANCE MEASURES FROM THE GRANT AGREEMENT PAGE 11 SCHEDULE G MEASURE VESSEL CALLS.CATEGORY AND DESCRIPTION ECONOMIC COMPETITIVENESS AND OPPORTUNITYTHE NUMBER OF VESSELS CALLING TO THE AREA DEFINED IN THE PROJECT STUDY AREA. MUST BE REPORTED IN TOTAL AND DISAGGREGATED BY ANY OF THE FOLLOWING WHERE APPLICABLE VESSEL TYPEG CONTAINER BULK RO RO LNG FREIGHT CAPACITY VESSEL LENGTH OR OTHER.MEASUREMENT FREQUENCY QUARTERLY. MEASURE CARGO DWELL TIME.CATEGORY AND DESCRIPTION ECONOMIC COMPETITIVENESS AND OPPORTUNITY AVERAGE CARGO DWELL TIME HOURS PER TON OR TEU. DWELL TIME IS DEFINED AS THE TIME BETWEEN CARGO ARRIVAL AND DEPARTURE BY VESSEL TRUCK OR RAIL. MEASUREMENT FREQUENCY QUARTERLY.MEASURE CLOSURE FROM NATURAL HAZARDS. CATEGORY AND DESCRIPTION STATE OF GOOD REPAIR TOTAL HOURS OF FACILITY CLOSURE PER YEAR. A CLOSURE IS DEFINED AS WHEN A NATURAL HAZARD PREVENTS A FACILITY FROM CONTINUING DAILY OPERATIONS OR SERVICE. MEASUREMENT FREQUENCY QUARTERLY. INTENDED BENEFICIARY CRESCENT CITY HARBOR DISTRIC. SUBRECIPIENT ACTIVITIES NONE.

THE PROJECT AIMS TO ENHANCE RAIL INFRASTRUCTURE AT PORT BIENVILLE INDUSTRIAL PARK IN HANCOCK COUNTY, MISSISSIPPI, THROUGH THE CONSTRUCTION OF AN EIGHT-TRACK CLASSIFICATION YARD AND A 3,500-LINEAR-FOOT INTERMODAL SWITCH LEAD. IT WILL IMPROVE RAILCAR STORAGE CAPACITY, STREAMLINE RAIL OPERATIONS, AND SUPPORT REGIONAL ECONOMIC GROWTH. KEY ACTIVITIES INCLUDE PRELIMINARY ENGINEERING (TO PREPARE DESIGNS, COST ESTIMATES, AND SCHEDULES FOR FRA APPROVAL), ENVIRONMENTAL REVIEW (TO COMPLETE NEPA COMPLIANCE AND RELATED DOCUMENTATION), FINAL DESIGN (TO DEVELOP DETAILED DESIGNS AND SECURE PERMITS FOR CONSTRUCTION), AND CONSTRUCTION (TO BUILD INFRASTRUCTURE WITH A CAPACITY FOR 235 RAILCARS, INCLUDING MITIGATION MEASURES). BENEFICIARIES INCLUDE LOCAL INDUSTRIES, RAIL OPERATORS, AND COMMUNITIES RELYING ON ENHANCED LOGISTICS NETWORKS FOR GROWTH AND OPPORTUNITY.

COMPUTATIONAL AND FUNCTIONAL APPROACHES TO VALIDATING CANCER GENOME TARGETS

CENTER FOR MALE REPRODUCTIVE EPIGENOMICS

VA IS PROVIDING PER DIEM FUNDING TO ASSIST WITH THE OPERATIONAL COSTS ASSOCIATED WITH TRANSITIONAL HOUSING BEDS FOR HOMELESS VETERANS.

SYSTEMS EPIGENOMICS OF PERSISTENT BLOODSTREAM INFECTION - PROJECT ABSTRACT PERSISTENT BLOODSTREAM INFECTIONS ARE LIFE-THREATENING INFECTIOUS DISEASE EMERGENCIES POSING SIGNIFICANT CHALLENGES TO EFFECTIVE TREATMENT. SUCH INFECTIONS OCCUR WHEN A PATHOGEN IS SUSCEPTIBLE TO AN ANTI-INFECTIVE AGENT IN VITRO BUT IS NOT CLEARED FROM THE BLOODSTREAM IN VIVO WHEN THAT ANTI-INFECTIVE AGENT IS USED APPROPRIATELY. AS A RESULT, ANTI-INFECTIVE USAGE INCREASES, ACCELERATING ALARMING INCREASES IN ANTI-INFECTIVE RESISTANCE. THIS VICIOUS CYCLE OF PERSISTENCE DRIVING ANTI- INFECTIVE ESCALATION DRIVING RESISTANCE IS AN NIH HIGH–PRIORITY CONCERN. BLOODSTREAM INFECTIONS CAUSED BY STAPHYLOCOCCUS AUREUS (SA) OR CANDIDA ALBICANS (CA) ARE INCREASINGLY COMMON. OF URGENT CONCERN, UP TO 35% OF PATIENTS WITH METHICILLIN-RESISTANT SA (MRSA) PERSISTENT BACTEREMIA SUCCUMB EVEN ON GOLD-STANDARD THERAPY. LIKEWISE, IN PATIENTS WITH HEMATOGENOUSLY DISSEMINATED CANDIDIASIS (HDC), MORTALITY IS 39% OVERALL AND 47% IN THOSE IN THE INTENSIVE CARE UNIT, DESPITE APPROPRIATE TREATMENT. A DISEASE MYSTERY IS CENTRAL TO SUCH INFECTIONS: THE CAUSATIVE PATHOGEN IS SUSCEPTIBLE TO ANTIMICROBIALS IN LABORATORY TESTING—BUT NOT IN THE HUMAN BEING. IMPORTANTLY, PERSISTENCE REFLECTS A UNIQUE TYPE OF TREATMENT-REFRACTORY INFECTIONS DISTINCT FROM CLASSICAL ANTIBIOTIC RESISTANCE. RATHER, PERSISTENT MRSA OR CA ARE ELUSIVE: THEY ADAPT TO HOST IMMUNE RESPONSES AND ANTIBIOTIC STRESSES UNIQUELY IN VIVO AND THEN REVERT QUICKLY IN VITRO. PRESENTLY, THERE ARE FEW THERAPEUTIC OPTIONS FOR PERSISTENT MRSA OR CA BLOODSTREAM INFECTIONS. HENCE, THERE IS A CRITICAL, UNMET NEED TO UNDERSTAND THE UNIQUE INTERACTIONS OF THE HUMAN, PATHOGEN AND THERAPEUTIC FACTORS DRIVING PERSISTENCE OUTCOMES. BASED ON OUR EXTENSIVE PRELIMINARY DATA, WE BELIEVE THAT PERSISTENT INFECTIONS CAUSED BY MRSA AND CA RESULT FROM A THREE-WAY INTERACTION OF THE PATHOGEN, HOST IMMUNE RESPONSE AND ANTIMICROBIAL AGENT IN VIVO. WE HYPOTHESIZE THAT PERSISTENT ISOLATES: 1) HAVE SPECIFIC EPIGENOMES TO ENABLE PERSISTENCE; 2) SUBVERT INNATE IMMUNE PROGRAMMING AND MEMORY FOR IMMUNE EVASION; 3) EVOKE NON-PROTECTIVE OR MALADAPTIVE IMMUNE RESPONSES; AND 4) EXPLOIT CONTEXTUAL IMMUNITY AS PERSISTENCE RESERVOIRS. WE FURTHER POSIT THAT CONVENTIONAL APPROACHES TO STUDY THIS CLINICALLY URGENT PHENOMENON ARE INSUFFICIENT TO UNDERSTAND IT. WE HAVE DEVELOPED THREE INDEPENDENT BUT SYNERGISTIC RESEARCH PROJECTS TO OVERCOME THESE LIMITATIONS. EACH PROJECT BRINGS PROVEN STRENGTHS AND INNOVATIVE APPROACHES TO BEAR ON SPECIFIC AIMS THAT SYNERGIZE VIA A SYSTEMS-BASED APPROACH SUPPORTED BY OUTSTANDING TECHNOLOGY, BIOINFORMATICS AND COMPUTATIONAL CORES. HERE, WE WILL USE STATE-OF-THE-ART TECHNOLOGIES TO COMPREHENSIVELY ANALYZE THE GENETICS AND EPIGENETICS OF PATHOGENS AND THE HOST IMMUNE SYSTEM IN CONTEXT OF ANTIMICROBIAL THERAPY IN LABORATORY STUDIES AND EXPERIMENTAL MODELS OF INFECTION. IN TURN, THESE DATA WILL BE ANALYZED USING POWERFUL BIOINFORMATICS AND COMPUTATIONAL METHODS TO DETECT HIDDEN PATTERNS WITHIN LARGE COMPLEX DATASETS. BY UNDERSTANDING THESE FACTORS AND THEIR INTERACTIONS, NEW APPROACHES TO IDENTIFY AND TREAT HIGH RISK PATIENTS CAN BE DEVELOPED AND APPLIED TO IMPROVE AND SAVE LIVES. THESE GOALS ARE IDEALLY ALIGNED WITH PRIORITIES OF THE NATIONAL INSTITUTES OF HEALTH AND CENTERS FOR DISEASE CONTROL & PREVENTION.

GRAMENE: A PLATFORM FOR COMPARATIVE PLANT GENOMICS

IRON UPTAKE AND MUCORMYCOSIS PATHOGENESIS

THE BASAL GANGLIA HABENULA CIRCUITRY IN REWARD PROCESSING

THE CENTRAL AMYGDALA CIRCUITS IN FEAR LEARNING AND FEAR EXPRESSION

PURPOSE: TO PROVIDE GRANTS TO COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS (CDFIS) FOR THE FOLLOWING PURPOSES 1) TO EXPAND LENDING, GRANT MAKING AND INVESTMENT ACTIVITIES IN LOW OR MODERATE INCOME COMMUNITIES AND TO BORROWERS THAT HAVE HISTORICALLY EXPERIENCED SIGNIFICANT UNMET CAPITAL AND FINANCIAL SERVICES NEEDS AND WERE DISPROPORTIONATELY IMPACTED BY THE COVID 19 PANDEMIC; AND 2) TO ENABLE CDFIS TO BUILD ORGANIZATIONAL CAPACITY AND ACQUIRE TECHNOLOGY, STAFF, AND OTHER TOOLS NECESSARY TO ACCOMPLISH THE ACTIVITIES UNDER A CDFI ERP AWARD. PLANNED ACTIVITIES: ELIGIBLE ACTIVITIES INCLUDE FINANCIAL PRODUCTS, FINANCIAL SERVICES, DEVELOPMENT SERVICES, GRANTS, LOAN LOSS RESERVES AND CAPITAL RESERVES THAT MAY BE USED TO MITIGATE THE IMPACT OF THE COVID 19 PANDEMIC ON UNEMPLOYMENT, CHILDCARE, HEALTHCARE, MENTAL HEALTHCARE, AFFORDABLE HOUSING, AFFORDABLE HOUSING FINANCE, SMALL BUSINESS, SMALL FARMS, BROADBAND INTERNET, AND FOOD SUFFICIENCY. IN ADDITION, TO SUPPORT CDFIS IN BUILDING THEIR CAPACITY TO RESPOND TO THE ECONOMIC IMPACT OF COVID 19, CDFI ERP AWARDS MAY BE USED FOR COMPENSATION PERSONAL SERVICES; COMPENSATION FRINGE BENEFITS; PROFESSIONAL SERVICE COSTS; TRAVEL COSTS; TRAINING AND EDUCATION COSTS; EQUIPMENT; SUPPLIES. END GOALS: EXPANDED FINANCING FOR LOW TO MODERATE INCOME COMMUNITIES AND INDIVIDUALS THAT HAVE HISTORICALLY EXPERIENCED SIGNIFICANT UNMET CAPITAL AND FINANCIAL SERVICES NEEDS AND WERE DISPROPORTIONATELY IMPACTED BY THE COVID 19 PANDEMIC INCLUDING SPECIFIC DESIGNATED COVID IMPACTED CDFI ERP ELIGIBLE GEOGRAPHIES AS AREAS THAT MAY BENEFIT FROM CDFI ERP ASSISTANCE. BENEFICIARIES: CERTIFIED CDFIS WHICH MAY BE FOR PROFIT ORGANIZATION, PRIVATE NONPROFIT INSTITUTION/ORGANIZATION, AND OTHER PRIVATE INSTITUTION/ORGANIZATION, AS DEFINED IN 12 C.F.R. 1805, AND LOW AND MODERATE INCOME INDIVIDUALS AND FAMILIES. SUBRECIPIENTS: THERE ARE NO SUBRECIPIENTS FOR THIS PROGRAM. BROADBAND: SPECIFIC ACTIVITIES RELATING TO BROADBAND USAGE ARE NOT KNOWN AT THE TIME OF AWARD. REASON/PURPOSE OF MODIFICATION: NOT APPLICABLE.

MAIZECODE - AN INITIAL ANALYSIS OF FUNCTIONAL ELEMENTS IN THE MAIZE GENOME

HISPANIC-SERVING INSTITUTIONS PROGRAM (STEM)

AMERICAN RESCUE PLAN ACT FUNDING FOR HEALTH CENTERS

FY 2023 DISASTER GRANT-WATER ONLY

PURPOSE: THE GREEN AND RESILIENT RETROFIT PROGRAM (GRRP) WAS ESTABLISHED BY SECTION 30002 OF THE INFLATION REDUCTION ACT OF 2022, (PUBLIC LAW 117-169) (THE “IRA”), TITLED “IMPROVING ENERGY EFFICIENCY OR WATER EFFICIENCY OR CLIMATE RESILIENCE OF AFFORDABLE HOUSING.” GRRP OFFERS LOANS AND GRANTS FOR HUD-ASSISTED MULTIFAMILY PROPERTIES TO IMPROVE ENERGY OR WATER EFFICIENCY, ENHANCE INDOOR AIR QUALITY OR SUSTAINABILITY, IMPLEMENT THE USE OF ZERO-EMISSION ELECTRICITY GENERATION, LOW-EMISSION BUILDING MATERIALS OR PROCESSES, ENERGY STORAGE, OR BUILDING ELECTRIFICATION STRATEGIES, OR ADDRESS CLIMATE RESILIENCE. ANNOUNCED GRRP AWARDS CAN BE FOUND AT WITHIN THE HYPERLINKED AWARDS ANNOUNCEMENT FOR EACH COHORT AT HTTPS://WWW.HUD.GOV/GRRP (E.G. WAVE 1 UNDER ELEMENTS AWARD ANNOUNCEMENT).; ACTIVITIES TO BE PERFORMED: GRRP FUNDS ARE USED TO FINANCE REHABILITATION PROJECTS THAT IMPROVE ENERGY OR WATER EFFICIENCY; ENHANCE INDOOR AIR QUALITY OR SUSTAINABILITY; IMPLEMENT THE USE OF ZERO-EMISSION ELECTRICITY GENERATION, LOW-EMISSION BUILDING MATERIALS OR PROCESSES, ENERGY STORAGE, OR BUILDING ELECTRIFICATION STRATEGIES; OR IMPROVE THE CLIMATE RESILIENCE OF ELIGIBLE HUD-ASSISTED MULTIFAMILY PROPERTIES. THESE AFFORDABLE HOUSING REHABILITATION PROJECTS MAY ENTAIL MOUNTING A ROOFTOP SOLAR SYSTEM TO GENERATE RENEWAL ENERGY, CONVERTING FROM GAS-POWERED HVAC SYSTEMS TO ELECTRIC HEAT PUMPS TO REDUCE CARBON EMISSIONS, AND/OR INSTALLING WIND- AND IMPACT-RESISTANT WINDOWS AND DOORS TO MAKE THEM RESILIENT TO SEVERE CLIMATE CONDITIONS –AMONG MANY OTHER ELIGIBLE MEASURES AND PROPERTY IMPROVEMENTS AIMED AT IMPROVING UTILITY EFFICIENCY, CLIMATE RESILIENCE, AND REDUCING CARBON EMISSIONS. THE PROGRAM SEEKS TO AMPLIFY RECENT TECHNOLOGICAL ADVANCEMENTS IN ENERGY AND WATER EFFICIENCY AND TO BRING A NEW FOCUS ON PREPARING FOR CLIMATE HAZARDS BY REDUCING RESIDENTS’ AND PROPERTIES’ EXPOSURE TO HAZARDS AND BY PROTECTING LIFE, LIVABILITY, AND PROPERTY WHEN DISASTER STRIKES. ALL GRRP INVESTMENTS WILL BE MADE IN AFFORDABLE HOUSING COMMUNITIES SERVING LOW-INCOME FAMILIES AND WILL REQUIRE AT LEAST FIVE YEARS OF EXTENDED AFFORDABILITY, AND A MINIMUM OF 15 YEARS OF AFFORDABILITY. HUD OFFERS GRRP FUNDING THROUGH THREE AWARD COHORTS DESIGNED TO MEET THE NEEDS OF PROPERTIES IN DIFFERENT SITUATIONS: ELEMENTS, LEADING EDGE, AND COMPREHENSIVE. APPROXIMATELY $140,000,000 WAS MADE AVAILABLE TO THE ELEMENTS COHORT, WHICH PROVIDES MODEST FUNDING TO OWNERS TO ADD PROVEN AND MEANINGFUL GREEN AND RESILIENT MEASURES TO THE CONSTRUCTION SCOPES OF IN-PROGRESS RECAPITALIZATION TRANSACTIONS. APPROXIMATELY $400,000,000 WAS MADE AVAILABLE TO THE LEADING EDGE COHORT, WHICH PROVIDES FUNDING FOR RETROFIT ACTIVITIES TO ACHIEVE AMBITIOUS OUTCOMES, INCLUDING GREEN BUILDING CERTIFICATION, NET ZERO, RENEWABLE ENERGY GENERATION, USE OF BUILDING MATERIALS WITH LOWER EMBODIED CARBON, AND CLIMATE RESILIENCE INVESTMENTS. APPROXIMATELY $1,470,000,000 WAS MADE AVAILABLE TO THE COMPREHENSIVE COHORT, WHICH PROVIDES FUNDING TO INITIATE RECAPITALIZATION INVESTMENTS DESIGNED FROM INCEPTION AROUND BOTH PROVEN AND INNOVATIVE GREEN AND RESILIENT MEASURES FOR PROPERTIES WITH A HIGH NEED FOR INVESTMENTS. UNDER ALL THREE AWARD COHORTS, OWNERS RECEIVE FUNDING IN THE FORM OF GRANTS OR LOANS. THROUGH 2024, GRRP WILL HAVE AWARDED ROUGHLY 250 PROPERTIES PRESERVING APPROXIMATELY 30,000 HOMES, THE MAJORITY OF WHICH ARE AFFORDABLE TO VERY LOW-INCOME HOUSEHOLDS, SENIORS, AND PERSONS WITH DISABILITIES.; EXPECTED OUTCOMES: THE PROGRAM WILL INCREASE ENERGY AND WATER EFFICIENCY, CREATE RENEWABLE ENERGY GENERATION, AND MAKE RESILIENCE IMPROVEMENTS TO PROTECT RESIDENTS AND AFFORDABLE HOUSING FROM NATURAL HAZARDS. TO MEASURE THIS, THE GRRP INVESTMENTS IMPLEMENTED ARE EXPECTED TO REDUCE GREENHOUSE GAS EMISSIONS BY 50% CUMULATIVELY ACROSS THESE PROPERTIES AND TO REDUCE MODELED ENERGY CONSUMPTION BY AT LEAST 25% AT EACH OF THESE PROPERTIES. SUCCESS OF THE GRRP GOALS WILL BE MEASURED USING EPA PORTFOLIO MANAGER’S UTILITY BENCHMARKING SYSTEM. INDIVIDUAL AWARDS WILL ENCOURAGE THE DEEPEST ENERGY SAVINGS AND EMISSIONS REDUCTIONS POSSIBLE BY FUNDING THE MOST IMPACTFUL IMPROVEMENTS IDENTIFIED THROUGH COMPREHENSIVE ASSESSMENTS OF THE BUILDINGS OR THROUGH ACHIEVING A TOP LEVEL, HIGH PERFORMANCE GREEN BUILDING CERTIFICATION. FURTHER, GRRP-FUNDED PROPERTY IMPROVEMENTS WILL ENHANCE RESIDENTS’ QUALITY OF LIFE AND PROVIDE HEALTHIER AND SAFER LIVING ENVIRONMENTS BY IMPROVING INDOOR AIR QUALITY, MAINTAINING COMFORTABLE LIVING TEMPERATURES, AND PREPARING BUILDINGS TO KEEP RESIDENTS SAFE THROUGH EXTREME WEATHER EVENTS AND NATURAL DISASTERS. RESILIENCE IMPROVEMENTS WILL BE CAPTURED BY A RESILIENCE ASSESSMENT THAT WILL BE REQUIRED FOR ALL GRRP PARTICIPANTS. RESILIENCE ASSESSMENT DATA MAY BE REPORTED FROM TIME TO TIME, BUT THERE ARE NO SPECIFIC PROGRAM GOALS FOR RESILIENCE. ; INTENDED BENEFICIARIES: THE PROGRAM AIMS TO BENEFIT RESIDENTS AND OWNERS OF HUD-ASSISTED MULTIFAMILY PROPERTIES AND THE COMMUNITIES AT-LARGE THEY RESIDE IN. THIS INCLUDES PROPERTIES ASSISTED BY SECTION 8 PROJECT-BASED RENTAL ASSISTANCE, SECTION 202 SUPPORTIVE HOUSING FOR LOW-INCOME ELDERLY, SECTION 811 SUPPORTIVE HOUSING FOR LOW-INCOME PERSONS WITH DISABILITIES PROGRAMS, AND SECTION 236 INTEREST REDUCTION PAYMENTS (IRP).; SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS.

CROSS-KINGDOM VACCINE TARGETING HEALTHCARE-ASSOCIATED PRIORITY PATHOGENS

UNKNOWN TITLE

TRPGR: MAIZE CELL GENOMICS: RESOURCES FOR VISUALIZING PROMOTER ACTIVITY AND PROTEIN DYNAMICS USING FLUORESCENT PROTEIN LINES

THE AGREEMENT ASSISTS BENTON HARBOR, MICHIGAN TO DEVELOP AND IMPLEMENT IMPROVEMENT INVESTMENTS THROUGH PROJECTS THAT WILL REDUCE LEAD EXPOSURE IN DRINKING WATER BY REPLACING HUNDREDS OF LEAD SERVICE LINES IN BENTON HARBOR, MICHIGAN.

BET BROMODOMAIN INHIBITION AS TARGETED THERAPY IN ACUTE MYELOID LEUKEMIA

SHORT AND LONG TERM OUTCOMES OF DOXYCYCLINE VERSUS TMP-SMX FOR SSTI TREATMENT

PROBING THE FUNCTION OF LONG NON-CODING RNAS IN DIFFERENTIATION

A HIGH-THROUGHPUT SEQUENCING AND IMAGING APPROACH TO UNDERSTAND THE FUNCTIONAL BASIS OF OLFACTION

A 3D MULTIMODAL MICRON-SCALE HUMAN BRAIN ATLAS BRIDGING SINGLE CELL DATA, NEUROPATHOLOGY AND NEURORADIOLOGY - DIGITIZED REFERENCE BRAINS, ALSO REFERRED TO AS COMMON COORDINATE FRAMEWORKS (CCFS), TOGETHER WITH SUPERPOSED ATLAS ANNOTATIONS, ARE OF CENTRAL IMPORTANCE TO NEUROSCIENCE. THEY BEAR THE SAME RELATION TO NEUROSCIENCE AS DO REFERENCE GENOMES AND GENOME ANNOTATIONS TO CELLULAR AND MOLECULAR BIOLOGY. STRIKINGLY, HOWEVER, SUCH REFERENCE BRAINS FOR HUMANS LAG FAR BEHIND THE CORRESPONDING CCFS FOR NON-HUMAN MODEL ORGANISMS SUCH AS THE LABORATORY MOUSE. EXISTING DATA SETS EITHER HAVE SECTIONS SPACED RELATIVELY FAR APART OR LACK IN-PLANE RESOLUTION DOWN TO THE MICRON SCALE. CRUCIALLY, EXISTING DATA SETS ARE NOT WELL CONNECTED TO THE MAJOR AREAS IN MEDICINE THAT DEAL WITH THE HUMAN BRAIN, NAMELY NEURORADIOLOGY AND NEUROPATHOLOGY. WE WILL MEET THIS NEED BY CREATING AN UNPRECEDENTED MICRON-SCALE, 3D ATLAS THAT COMBINES MULTIPLE MRI MODALITIES AS WELL AS CONTINUOUS SERIAL SECTION HISTOLOGY. IN PARTICULAR, THE REFERENCE ATLAS WILL CONSIST OF NISSL, MYELIN AND H&E STAINS, WITH 20 MICRON CONTIGUOUS SERIAL SECTIONS, AND APPROXIMATELY ~8000 SECTIONS/BRAIN. WE WILL DO SO USING THE TAPE-TRANSFER METHOD, WHICH PRESERVES TISSUE GEOMETRY EVEN IN THE PRESENCE OF DISCONNECTED PIECES TO THE BRAIN BEING SECTIONED, AND PERMITS 3D REASSEMBLY OF THE SECTIONS INTO A 3D VOLUME. WE WILL UTILIZE DIFFEOMORPHIC MAPPING METHODS TO CO-REGISTER THE MRI AND HISTOLOGICAL DATA, AND WILL CREATE A HUMAN BRAIN CCF IN WHICH SINGLE-CELL TRANSCRIPTOMIC AND EPIGENOMIC DATA CAN BE PINNED IN ORDER TO CREATE A HUMAN BRAIN CELL ATLAS. WE WILL USE MACHINE LEARNING APPROACHES TO SEGMENT CELLS AND PROCESSES IN THESE IMAGES AND TO ALGORITHMICALLY DETECT CYTOARCHITECTONIC BOUNDARIES; SUCH MACHINE LEARNING METHODS WILL ALSO BE USED TO PREDICT HISTOLOGY AND CYTOARCHITECTURE FROM MRI DATA, WITH OUR COLLECTED DATA AS A TRAINING SET. WE WILL MAKE OUR DATA FREELY AVAILABLE TO SCIENTISTS AS WELL AS MEDICAL PROFESSIONALS THROUGH AN ONLINE DATA PORTAL WITH A MULTI-RESOLUTION VIEWER FOR ZOOMING AND PANNING THROUGH TERAPIXEL IMAGE DATA, AND ALSO DEPOSIT THE DATA IN A SHARED DATA REPOSITORY TO MAKE IT EASILY ACCESSIBLE TO OTHER RESEARCHERS. WE WILL CONNECT OUR DATA TO A UNIQUE ON-LINE NEUROPATHOLOGY RESOURCE CONTAINING OVER A PETABYTE OF NEUROPATHOLOGICAL IMAGES, INCLUDING H&E STAINED SECTIONS FROM THE CORONAL PLANE. WE EXPECT THAT THE REFERENCE BRAIN DATA WE PRODUCE WILL BECOME THE DE- FACTO STANDARD FOR A HIGH-RESOLUTION REFERENCE ATLAS FOR THE HUMAN BRAIN.

MAKING HYPOMORPHIC TUMOR SUPRESSORS IN VIVO USING RNAI

COMPUTATIONAL AND GENOMIC RESOURCES TO SUPPORT PLANT GENOME FUNCTION - TO GENERATE RESOURCES AND ACCELERATE OUR UNDERSTANDING OF GENOME FUNCTION.

BIOCHEMISTRY OF PRE-MRNA SPLICING

UNKNOWN TITLE

THE PORT OF HUENEME'S MARINE TERMINALS HANDLE AUTOMOBILES, CONTAINERIZED CARGO (PRIMARILY FRUIT), BREAK BULK FRUIT AND GENERAL CARGO (INCLUDING PROJECT CARGO, MILITARY CARGO AND LIQUID FERTILIZER). THIS PROJECT WILL PROVIDE LONG-TERM INFRASTRUCTURE ENHANCEMENTS THAT MAXIMIZE FACILITY UTILIZATION. IT WILL ALSO MODERNIZE THE WHARF AND PIER STRUCTURE TO MITIGATE MODERATE SEISMIC EPISODES AND CLIMACTIC RESILIENCY. THE PROJECT IS A COLLABORATION BETWEEN PRIVATE AND PUBLIC SECTOR PARTNERS TO STRATEGICALLY DEVELOP MARINE TERMINAL INFRASTRUCTURE THAT DIVERSIFIES FREIGHT MODAL CHOICES, ACCOMMODATES CUSTOMER DEMAND FOR INCREASED CARGO CAPACITY AND FOSTERS AN ENVIRONMENT THAT FULLY UTILIZES EXISTING ASSETS WITHIN THE MARINE TERMINAL COMPLEX. THE PORT'S THREE LARGEST FRESH PRODUCE CUSTOMERS HAVE ALL EXPRESSED INTEREST IN UTILIZING THE ADDITIONAL BERTH THAT THE PROJECT WOULD CREATE. THE APPLICANT ESTIMATES THE PROJECT WILL CREATE 113 JOBS AND RETAIN 417 JOBS.

RYAN WHITE PART C OUTPATIENT EIS PROGRAM

CAPITAL DEVELOPMENT

TRUE NORTH- FORGING PATHWAYS TO HEALTHY RELATIONSHIPS & ECONOMIC STABILITY

CARES ACT INSTITUTIONAL FUNDING FOR GHC

EPIGENETIC REGULATION OF SEX DIFFERENCES IN THE BRAIN

RESEARCH-PGR: DISSECTING THE DYNAMIC EVOLUTION OF PARALOGS IN SHAPING TRAIT VARIATION ACROSS THE SOLANUM PAN-GENOME -THE GROWING POPULATION AND CLIMATE EXTREMES ARE THREATENING FOOD SECURITY. AGRICULTURE IS LARGELY BASED ON A FEW MAJOR CROPS, AND REVOLUTIONARY TECHNOLOGIES IN GENOME SEQUENCING AND CRISPR GENOME ENGINEERING ARE ACCELERATING THEIR IMPROVEMENT. THESE TECHNOLOGIES CAN ALSO IMPROVE ?ORPHAN? CROPS, WHICH ARE NOT WIDELY CULTIVATED OR STUDIED BUT HAVE THE POTENTIAL TO INCREASE THE DIVERSITY AND RESILIENCE OF FOOD PRODUCTION. ORPHAN CROPS ARE RELATED TO MAJOR CROPS, ALLOWING TRANSLATION OF KNOWLEDGE BETWEEN THEM. HOWEVER, ORPHAN CROPS LACK RESEARCH TOOLS, AND AN EVEN GREATER CHALLENGE IS DETERMINING WHETHER SPECIFIC GENETIC MUTATIONS THAT BENEFITTED MAJOR CROPS CAN BE ENGINEERED TO IMPROVE TRAITS SIMILARLY IN ORPHAN CROPS. THIS IS BECAUSE GENE SEQUENCE AND FUNCTION CHANGE AS SPECIES EVOLVE, ESPECIALLY AMONG GENES THAT BECOME DUPLICATED, WHICH IS COMMON IN PLANTS. THIS PROJECT WILL TAKE ADVANTAGE OF THE NIGHTSHADE FAMILY ? A SOURCE OF MANY MAJOR AND ORPHAN CROPS, SUCH AS EGGPLANT, PEPINO, AND TOMATO ? TO STUDY HOW DUPLICATED GENES EVOLVE AND AFFECT AGRICULTURAL TRAITS IN RELATED SPECIES. COMBINING GENOME SEQUENCING AND CRISPR WILL REVEAL SEQUENCE DIVERSITY AMONG THOUSANDS OF DUPLICATED GENES AND ENABLE IMPROVED PREDICTABILITY IN ENGINEERING GENES AND TRAITS ACROSS SPECIES. THIS PROJECT WILL TRAIN YOUNG SCIENTISTS WITH A FOCUS ON DIVERSITY AND INCLUSION, AS WELL AS PROMOTE PUBLIC UNDERSTANDING OF GENOME ENGINEERING IN PLANT BIOLOGY THROUGH A COMMUNITY SCIENCE PROGRAM ON ORPHAN CROPS. FINALLY, NEW CURRICULA AND RESEARCH OPPORTUNITIES FOR UNDERGRADUATE STUDENTS AT A SMALL LIBERAL ARTS COLLEGE WILL BROADEN PARTICIPATION AND TRAINING OF UNDERREPRESENTED GROUPS IN THE PLANT SCIENCES. THIS PROJECT WILL EXPLOIT ADVANCES IN LARGE-SCALE REFERENCE GENOME SEQUENCING, GENE CO-EXPRESSION ANALYSES, AND CRISPR GENOME EDITING TO DISSECT HOW PARALOG DIVERSIFICATION IMPACTS SPECIES-SPECIFIC PHENOTYPES IN A GENUS OF BOTH FUNDAMENTAL AND APPLIED IMPORTANCE. FIFTY SOLANUM SPECIES, INCLUDING 16 ORPHAN CROPS, WILL BE SEQUENCED TO ESTABLISH A SOLANUM PAN-GENOME WITH TELOMERE-TO-TELOMERE REFERENCE ASSEMBLIES, PROVIDING A FOUNDATION FOR GENUS-WIDE COMPARATIVE GENOMICS AND FUNCTIONAL GENETICS. COMPUTATIONAL APPROACHES BASED ON GENOMICS DATA WILL BE DEVELOPED FOR PRECISE ASSEMBLY AND COMPARISON OF COMPLEX GENOMES, AND IDENTIFICATION AND CLASSIFICATION OF PARALOGS AND THEIR RELATIONSHIPS BASED ON THEIR VARIANTS AND EXPRESSION PATTERNS. SIMULTANEOUSLY, TRANSFORMATION PROTOCOLS AND GENOME EDITING WILL BE DEVELOPED AND DEPLOYED FOR AN ARRAY OF SOLANUM TO TEST HOW PARALOGS IMPACT GENOTYPE-TO-PHENOTYPE RELATIONSHIPS WITHIN AND BETWEEN SPECIES. BY FOCUSING ON MAJOR DOMESTICATION GENE FAMILIES AND THE ADAPTATION AND PRODUCTIVITY TRAITS THEY CONTROL, THIS SYNERGISTIC WORK WILL PROVIDE BOTH A NEW UNDERSTANDING OF PARALOG DIVERSIFICATION IN EVOLUTION AND A MORE ROBUST TRANSLATION OF AGRICULTURALLY RELEVANT GENOTYPE-TO-PHENOTYPE RELATIONSHIPS TO ORPHAN CROPS. BEYOND A VALUABLE COMMUNITY RESOURCE OF SOLANUM REFERENCE GENOMES, EXPRESSION DATA, AND CRISPR LINES FOR PLANT RESEARCHERS AND BREEDERS, THIS MULTIDISCIPLINARY PROJECT WILL RESULT IN NEW TOOLS, RESOURCES, AND PRINCIPLES THAT WILL ENABLE THE STUDY AND ENGINEERING OF OTHER TAXA AND TRAITS OF SIGNIFICANCE TO BOTH PLANT BIOLOGY AND CROP IMPROVEMENT. 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.

UNKNOWN TITLE

CSHL MOLECULAR TARGET DISCOVERY AND DEVELOPMENT CENTER

RESEARCH PGR: STRUCTURAL VARIANT LANDSCAPES IN TOMATO GENOMES AND THEIR ROLE IN NATURAL VARIATION, DOMESTICATION AND CROP IMPROVEMENT

EVOLUTIONARY HUMAN GENOMICS: DEMOGRAPHY, NATURAL SELECTION, AND TRANSCRIPTIONAL REGULATION

DOCK7 SIGNALING IN NEURONAL DEVELOPMENT

RESEARCH-PGR: DISSECTING THE GENOMIC ARCHITECTURE OF FUNCTIONAL REDUNDANCY TO MODULATE MERISTEM HOMEOSTASIS AND CROP YIELDS

CAPITAL DEVELOPMENT

RNAI, HISTONE MODIFICATION AND THE DDB1/CPSF-LIKE COMPLEX RIK1

DOMESTIC WATER GRANTS - REGULAR

DOMESTIC WATER GRANTS - REGULAR

UNDERSTANDING THE LOGIC OF THE BRAIN-WIDE OLFACTORY BULB PROJECTOME

TARGETING THE TUMOR MICROENVIRONMENT TO TERMINATE DRUG RESISTANT BREAST CANCER

BIOLOGICAL DESIGN OF LEMNACEAE AGUATIC PLANTS FOR BIODIESEL PRODUCTION

IND-ENABLEMENT OF KINOCIDIN GAMMA-RP-1 FOR MDR GRAM-NEGATIVE INFECTIONS

THE MISSING CIRCUIT: THE FIRST BRAINWIDE CONNECTIVITY MAP FOR MOUSE

IMPROVE EXISTING AIRPORT

HARBOR COMMUNITY MENTAL HEALTH CENTERS GRANT PROGRAM - HARBOR'S COMMUNITY MENTAL HEALTH CENTERS (CMHC) GRANT PROGRAM WILL PROVIDE CONTINUED DELIVERY OF, AND ACCESS TO, OUR COMPREHENSIVE MENTAL HEALTH AND SUBSTANCE USE DISORDER SERVICES, EFFECTIVE CRISIS INTERVENTION AND STABILIZATION, CARE COORDINATION, INCREASED UTILIZATION OF EVIDENCE-BASED PRACTICES, IMPROVEMENT OF BEHAVIORAL HEALTH OUTCOMES, AND SUPPORT TO ESSENTIAL CARE STAFF. THIS PROGRAM WILL ALLOW HARBOR TO STRENGTHEN INFRASTRUCTURE FOR TELEHEALTH SERVICES, EXPAND ACCESS TO TRAUMA-INFORMED SERVICES, PROVIDE RESOURCES FOR THE MENTAL HEALTH NEEDS OF OTHER CMHC STAFF, ENHANCE TRAINING IN HEALTH EQUITY, EXPAND CRISIS RESPONSE CAPABILITIES IN LUCAS COUNTY, AND ENHANCE OUTREACH WITH LOCAL SCHOOLS AND HOMELESS SHELTERS THROUGH EMBEDDED CLINICIANS. OUR POPULATION OF FOCUS WILL BE LUCAS COUNTY RESIDENTS DIAGNOSED WITH A SERIOUS MENTAL ILLNESS (SMI) OR SUBSTANCE USE DISORDER (SUD); YOUTH WITH SERIOUS EMOTIONAL DISTURBANCE (SED); INDIVIDUALS WITH CO-OCCURRING DISORDERS (COD); AND INDIVIDUALS NEEDING CRISIS INTERVENTION SERVICES. WE WILL SERVE 650 INDIVIDUALS IN THE FIRST YEAR AND 850 IN YEAR TWO FOR A TOTAL OF 1,500 UNDUPLICATED INDIVIDUALS SERVED, AND WILL ADDITIONALLY TARGET ESSENTIAL WORKERS AND SCHOOL PERSONNEL THROUGH TRAININGS, WORKSHOPS, AND EAP SERVICES. PROJECT GOALS INCLUDE: (1) IMPROVING ACCESS TO CARE WITH THE DAYS BETWEEN REQUEST FOR ROUTINE CARE AND INITIAL ASSESSMENT DECREASING TO 7 DAYS, INCREASING USE OF THE MYSTRENGTH WELLNESS APP. AND NUMBER OF EMERGENCY DEPARTMENT VISITS REDUCED BY 5% PER VALUE BASED CONTRACT (VBC) DATA; (2) IMPROVED CLIENT LEVEL OF FUNCTIONING WITH 75% OF ENROLLED CLIENTS DEMONSTRATING IMPROVEMENT ON STANDARDIZED ASSESSMENT TOOLS FROM ADMISSION TO MOST RECENT, 90% OF ENROLLED CLIENTS RECEIVING CARE THAT INCORPORATES USE OF EVIDENCE BASED PRACTICE (EBP), AND 80% OF ELIGIBLE CLINICIANS BEING TRAINED IN AT LEAST 2 EBPS; (3) ENHANCED OUTREACH EFFORTS TO EFFECTIVELY ENGAGE UNDERSERVED AND AT-RICK POPULATIONS WITH CLINICIANS EMBEDDED AT DESIGNATED TOLEDO PUBLIC SCHOOLS AND THE HOMELESS SHELTER AND COORDINATION OF AT LEAST 6 HEALTH EQUITY EVENTS; AND (4) ESSENTIAL WORKERS HAVING ACCESS TO EAP SERVICES AND SUPPORTS WITH 100 ESSENTIAL WORKERS ENGAGING IN SERVICES, 24 EAP TRAININGS PROVIDED TO ESSENTIAL WORKERS, AND 85% OF TRAINING PARTICIPANTS INDICATING THESE WORKSHOPS MET THEIR STATED OBJECTIVES. THIS PROJECT WILL FOCUS ON ESTABLISHING A PSYCHIATRIC URGENT CARE CENTER WITH ACCESS TO EVALUATIONS FROM MD/NP AND CRISIS STABILIZATION UNIT TO MEET THE IDENTIFIED NEED IN OUR COUNTY FOR AN IMPROVED CONTINUUM OF CRISIS SERVICES AS WELL AS ENGAGING EFFECTIVELY WITH OUR DIVERSE COMMUNITY, INCLUDING THOSE POPULATIONS WHO MAY BE UNDERSERVED, BY LISTENING AND UNDERSTANDING DIFFERENT PERSPECTIVES ON ACCESS TO CARE AND SERVICES AND INVOLVING OTHER COMMUNITY ORGANIZATIONS IN THE EVOLUTION OF THE COMMUNITY NETWORK. HARBOR HAS A VAST CONTINUUM OF SERVICES AND HISTORY OF 100+ YEARS IN DELIVERING HIGH-QUALITY SERVICES, EXPERTISE IN DEVELOPING AND EXPANDING COMPLEX PROGRAMS, EXPERIENCE DEVELOPING AND MANAGING DATA COLLECTION AND REPORTING REQUIREMENTS, AND ONGOING COLLABORATIONS WITH A MULTITUDE OF COMMUNITY AGENCIES WHICH POSITIONS OUR AGENCY TO ACHIEVE THE GOALS OF THIS GRANT.

WASTE DISPOSAL GRANTS - REGULAR

HISPANIC-SERVING INSTITUTIONS PROGRAM (STEM)

STRUCTURE AND FUNCTION OF HETERO-MULTIMERIC LIGAND-GATED ION CHANNELS

CSHL-JAX PATIENT-DERIVED MODELS OF PANCREATIC CANCER AS SYSTEMS FOR INVESTIGATING TUMOR HETEROGENEITY

COLD SPRING HARBOR LABORATORY CANCER WORKSHOPS

AWARD PURPOSE THIS PROJECT WILL CONSTRUCT A NEW RAIL STORAGE YARD TO SUPPORT THE EXISTING OPERATIONS AT THE PORT FACILITY. THE PROJECT WOULD ADD APPROXIMATELY 130 ADDITIONAL STORAGE SPACES CONSTRUCT TWO SETS OF STORAGE TRACKS AND A NEW RAIL SIDING. THESE ADDITIONAL SPACES ARE EXPECTED TO INCREASE THE RECIPIENTS STORAGE CAPACITY BY 25 PERCENT SO THAT IT CAN SAFELY MANAGE THE CURRENT STORAGE OPERATIONS AND MEET THE CURRENT REPRESSED STORAGE DEMAND. ACTIVITIES TO BE PERFORMED THE PROJECT WILL ADD 130 ADDITIONAL STORAGE SPACES BY CONSTRUCTING TWO SETS OF STORAGE TRACKS AND A RAIL SIDING. THIS PROJECT IS MADE UP OF THE FOLLOWING TWO COMPONENTS. COMPONENT 1 DESIGN AND PROJECT ADMINISTRATION OF PORT BIENVILLE RAIL STORAGE YARD COMPLETION OF PRELIMINARY STUDIES AND SURVEYS TOPOGRAPHIC SURVEY GEOTECHNICAL INVESTIGATION JURISDICTIONAL DETERMINATION WETLANDS DELINEATION CULTURAL RESOURCES SURVEY THREATENED AND ENDANGERED SPECIES SURVEY HAZARDS AND TOXICS SURVEY PRELIMINARY DESIGN 30 PERCENT OTHER ENVIRONMENTAL TASKS USACE 404 PERMIT AND ENVIRONMENTAL ASSESSMENT OPINION OF PROBABLE CONSTRUCTION COSTS AND FINAL DESIGN 60 PERCENT 90 PERCENT 100 PERCENT. PREPARATION OF CONSTRUCTION DRAWINGS CONTRACT DOCUMENT AND TECHNICAL SPECIFICATIONS TO BE USED FOR PROCUREMENT. ASSISTANCE WITH PROCUREMENT AND CONTRACT AWARD FOR COMPONENT 2 CONSTRUCTION OF RAIL STORAGE YARD. ENGINEER TO PROVIDE CONSTRUCTION ADMINISTRATION AND RESIDENT PROJECT REPRESENTATION THROUGHOUT CONSTRUCTION OF THE PROJECT FINAL INSPECTION ACTIVITIES ASSIST WITH CONTRACTORS COMPLETION OF PUNCH LIST ITEMS AND ASSIST WITH CLOSEOUT AT THE CONCLUSION OF CONSTRUCTION. COMPONENT 2 CONSTRUCTION OF RAIL STORAGE YARD. INSTALLATION OF APPROXIMATELY 13800 LINEAR FEET OF ADDITIONAL TRACK NINE TURNOUTS ROUGHLY 8263 STEEL OR TIMBER TIES AND APPROXIMATELY 12168 TONS OF BALLAST. DELIVERABLES WITHIN ECONOMIC COMPETITIVENESS. FREIGHT MOVEMENTS NUMBER OF TEU RAILCAR TRUCK MOVEMENTS OVER PROJECT STUDY AREA CARGO STORAGE TOTAL CARGO STORAGE FOR PROJECT STUDY AREA INTENDED BENEFICIARY HANCOCK COUNTY PORT AND HARBOR COMMISSION SUBRECIPIENTS NONE.

GREEN AND RESILIENT RETROFIT PROGRAM

RYAN WHITE PART C OUTPATIENT EIS PROGRAM

A UNIFIED QUANTITATIVE MODELING STRATEGY FOR MULTIPLEX ASSAYS OF VARIANT EFFECT - PROJECT SUMMARY / ABSTRACT A CENTRAL GOAL OF GENOMICS IS TO UNDERSTAND THE RELATIONSHIP BETWEEN GENOTYPE AND PHENOTYPE. IN RECENT YEARS, THE ABILITY TO QUANTITATIVELY STUDY GENOTYPE-PHENOTYPE MAPS HAS BEEN REVOLUTIONIZED BY THE DEVELOPMENT OF MULTIPLEX ASSAYS OF VARIANT EFFECT (MAVES), WHICH MEASURE MOLECULAR PHENOTYPES FOR THOUSANDS TO MILLIONS OF GENOTYPIC VARIANTS IN PARALLEL. MAVE IS AN UMBRELLA TERM THAT INCLUDES MASSIVELY PARALLEL REPORTER ASSAYS FOR STUDIES OF DNA OR RNA REGULATORY SEQUENCES, AS WELL AS DEEP MUTATIONAL SCANNING ASSAYS OF PROTEINS OR STRUCTURAL RNAS. THE RAPID ADOPTION OF MAVE TECHNIQUES ACROSS MULTIPLE GENOMIC DISCIPLINES HAS CREATED AN ACUTE NEED FOR COMPUTATIONAL METHODS THAT CAN ROBUSTLY AND REPRODUCIBLY INFER QUANTITATIVE GENOTYPE- PHENOTYPE (G-P) MAPS FROM THE LARGE DATASETS THAT MAVES PRODUCE. HERE WE PROPOSE A UNIFIED CONCEPTUAL AND COMPUTATIONAL FRAMEWORK FOR QUANTITATIVELY MODELING G-P MAPS FROM MAVE DATA. THIS PROPOSAL IS MOTIVATED BY OUR REALIZATION THAT ACCOUNTING FOR THE NOISE AND NONLINEARITIES THAT ARE OMNIPRESENT IN MAVE EXPERIMENTS REQUIRES EXPLICIT MODELING OF BOTH THE MAVE MEASUREMENT PROCESS AND THE G-P MAP OF INTEREST. THIS JOINT INFERENCE STRATEGY IS MORE COMPUTATIONALLY DEMANDING THAN MOST MAVE ANALYSIS METHODS, BUT IT IS FEASIBLE USING MODERN DEEP LEARNING FRAMEWORKS. OUR EXTENSIVE PRELIMINARY DATA SHOW THAT THIS MODELING STRATEGY IS ABLE TO RECOVER HIGH-PRECISION G-P MAPS EVEN IN THE PRESENCE OF MAJOR CONFOUNDING EFFECTS, AND THUS HAS THE POTENTIAL TO BENEFIT MAVE STUDIES IN MULTIPLE AREAS OF GENOMICS. AIM 1 WILL DEVELOP METHODS FOR MODELING THE MEASUREMENT PROCESSES THAT ARISE IN DIVERSE MAVE EXPERIMENTAL DESIGNS. AIM 2 WILL DEVELOP GENERAL METHODS FOR MODELING GENETIC INTERACTIONS WITHIN G-P MAPS, AND WILL USE THESE METHODS IN CONJUNCTION WITH NEW EXPERIMENTS TO ELUCIDATE THE MOLECULAR MECHANISM OF A RECENTLY APPROVED DRUG THAT TARGETS ALTERNATIVE MRNA SPLICING. AIM 3 WILL DEVELOP METHODS FOR INFERRING G-P MAPS THAT REFLECT BIOPHYSICAL MODELS OF GENE REGULATION, INCLUDING BOTH THERMODYNAMIC (I.E., QUASI-EQUILIBRIUM) AND KINETIC (I.E., NON-EQUILIBRIUM STEADY-STATE) MODELS. THESE METHODS WILL THEN BE USED, IN CONJUNCTION WITH NEW MAVE EXPERIMENTS, TO DEVELOP A BIOPHYSICAL MODEL FOR HOW A PLEIOTROPIC TRANSCRIPTION FACTOR REGULATES GENE EXPRESSION THROUGHOUT THE ESCHERICHIA COLI GENOME. AIM 4 WILL STUDY AND DEVELOP METHODS FOR TREATING GAUGE FREEDOMS AND SLOPPY MODES IN THE ABOVE CLASSES OF MODELS, THEREBY FACILITATING THE COMPARISON, INTERPRETATION, AND EXPLORATION OF INFERRED G-P MAPS. ALL OF THE COMPUTATIONAL TECHNIQUES WE DEVELOP WILL BE INCORPORATED INTO A ROBUST AND EASY- TO-USE PYTHON PACKAGE CALLED MAVE-NN. WE WILL BENCHMARK MAVE-NN ON A DIVERSE ARRAY OF MAVE DATASETS, INCLUDING PUBLISHED DATASETS AND DATA GENERATED AS PART OF THIS PROJECT. IN ALL, THIS WORK WILL FILL A MAJOR NEED IN THE ANALYSIS OF MAVE EXPERIMENTS, YIELDING A ROBUST, FLEXIBLE, AND SCALABLE COMPUTATIONAL PLATFORM THAT WILL HELP ACCELERATE THE USE OF MAVES FOR UNDERSTANDING THE EFFECTS OF HUMAN GENETIC VARIATION AT THE GENOMIC SCALE.

RESEARCH-PGR/NSF-BSF: IDENTIFICATION AND FUNCTIONAL DISSECTION OF SHARED CIS-REGULATORY ELEMENTS CONTROLLING QUANTITATIVE TRAIT VARIATION ACROSS ANGIOSPERMS

THE SSVF PROGRAM'S PURPOSE IS TO PROVIDE SUPPORTIVE SERVICES GRANTS TO PRIVATE NON-PROFIT ORGANIZATIONS AND CONSUMER COOPERATIVES, WHO WILL COORDINATE OR PROVIDE SUPPORTIVE SERVICES TO VERY LOW-INCOME VETERAN FAMILIES WHO ARE RESIDING IN PERMANENT HOUSING, ARE HOMELESS AND SCHEDULED TO BECOME RESIDENTS OF PERMANENT HOUSING WITHIN A SPECIFIED TIME PERIOD; OR AFTER EXITING PERMANENT HOUSING WITHIN A SPECIFIED TIME PERIOD, ARE SEEKING OTHER HOUSING THAT IS RESPONSIVE TO SUCH VERY LOW-INCOME VETERAN FAMILY'S NEEDS AND PREFERENCES. GRANTEES WILL USE SUPPORTIVE SERVICES GRANT FUNDS TO PROVIDE SUPPORTIVE SERVICE. ALL GRANTEES ARE REQUIRED TO PROVIDE OUTREACH SERVICES, CASE MANAGEMENT SERVICES, ASSISTANCE IN OBTAINING VA BENEFITS AND ASSISTANCE IN OBTAINING AND COORDINATING OTHER PUBLIC BENEFITS. IN ADDITION TO THE REQUIRED SERVICES, GRANTEES MAY ALSO PROVIDE TEMPORARY FINANCIAL ASSISTANCE PAID DIRECTLY TO A THIRD PARTY ON BEHALF OF A PARTICIPANT FOR CHILD CARE, EMERGENCY HOUSING ASSISTANCE, TRANSPORTATION, RENTAL ASSISTANCE, UTILITY-FEE PAYMENT ASSISTANCE, SECURITY DEPOSITS, UTILITY DEPOSITS, MOVING COSTS, AND GENERAL HOUSING STABILITY ASSISTANCE (WHICH INCLUDES EMERGENCY SUPPLIES), IN ACCORDANCE WITH 38 CFR PART 62. ADDITIONAL OPTIONAL SUPPORTIVE SERVICES MAY INCLUDE LEGAL ASSISTANCE AND FINANCIAL MANAGEMENT SERVICES. GRANTEES WILL USE SUPPORTIVE SERVICES GRANT FUNDS TO PROVIDE SUPPORTIVE SERVICE. ALL GRANTEES ARE REQUIRED TO PROVIDE OUTREACH SERVICES, CASE MANAGEMENT SERVICES, ASSISTANCE IN OBTAINING VA BENEFITS AND ASSISTANCE IN OBTAINING AND COORDINATING OTHER PUBLIC BENEFITS. IN ADDITION TO THE REQUIRED SERVICES, GRANTEES MAY ALSO PROVIDE TEMPORARY FINANCIAL ASSISTANCE PAID DIRECTLY TO A THIRD PARTY ON BEHALF OF A PARTICIPANT FOR CHILD CARE, EMERGENCY HOUSING ASSISTANCE, TRANSPORTATION, RENTAL ASSISTANCE, UTILITY-FEE PAYMENT ASSISTANCE, SECURITY DEPOSITS, UTILITY DEPOSITS, MOVING COSTS, AND GENERAL HOUSING STABILITY ASSISTANCE (WHICH INCLUDES EMERGENCY SUPPLIES), IN ACCORDANCE WITH 38 CFR PART 62. ADDITIONAL OPTIONAL SUPPORTIVE SERVICES MAY INCLUDE LEGAL ASSISTANCE AND FINANCIAL MANAGEMENT SERVICES.

OSCILLATORY GENE EXPRESSION AND THE MAINTENANCE OF TEMPORAL PATTERNING

HARBOR-CCBHC PLANNING, DEVELOPMENT, AND IMPLEMENTATION GRANT - HARBOR'S CERTIFIED COMMUNITY BEHAVIORAL HEALTH CLINIC (CCBHC) GRANT PROGRAM WILL PROVIDE CONTINUED DELIVERY OF OUR COMPREHENSIVE MENTAL HEALTH AND SUBSTANCE USE SERVICES, DEVELOPMENT OF A DEDICATED CARE COORDINATION TEAM, INCREASED USE OF EVIDENCE-BASED PRACTICES, AND EXPANDED ACCESS TO 24/7 PSYCHIATRIC URGENT CARE SERVICES. THIS PROGRAM WILL ALLOW HARBOR TO BRING EXTENSIVE CARE COORDINATION ACROSS PROVIDERS, COMPLEX DATA TRACKING, EXPANDED USE OF RELEVANT EVIDENCE-BASED PRACTICES, AND POPULATION HEALTH MANAGEMENT TO LUCAS COUNTY. OUR POPULATION OF FOCUS WILL BE ADULTS AND YOUTH IN LUCAS COUNTY WITH MEDICAID COVERAGE AND THOSE WHO ARE UNINSURED OR UNDERINSURED AND HAVE BEEN DIAGNOSED WITH A SERIOUS MENTAL ILLNESS (SMI) OR SUBSTANCE USE DISORDER (SUD), CHILDREN AND ADOLESCENTS WITH SERIOUS EMOTIONAL DISTURBANCE (SED), AND INDIVIDUALS WITH CO-OCCURRING DISORDERS. WE WILL SERVE 200 INDIVIDUALS IN THE FIRST YEAR AND A TOTAL OF 1,300 UNDUPLICATED INDIVIDUALS ACROSS THE ENTIRE FOUR-YEAR GRANT. PROJECT GOALS INCLUDE: (1) IMPROVING ACCESS TO CARE AND CARE COORDINATION SERVICE WITH 10 FORMAL COORDINATION AGREEMENTS WITH LOCAL AGENCIES BEING IN PLACE AND RECOVERY PLAN TOOLS BEING AVAILABLE IN THE EHR; (2) IMPROVED CLIENT BEHAVIORAL HEALTH OUTCOMES WITH 70% OF ENROLLED CLIENTS DEMONSTRATING IMPROVEMENT ON STANDARDIZED ASSESSMENT TOOLS FROM ADMISSION TO MOST RECENT AND 90% OF CCBHC CLIENTS RECEIVING CARE THAT INCORPORATES USE OF AN EVIDENCE-BASED PRACTICE; (3) IMPROVED ACCESS TO IMMEDIATE CRISIS CARE WITH PSYCHIATRIC URGENT CARE STAFFING EXPANDING TO 24/7 COVERAGE, 95% OF URGENT CARE CLIENTS HAVING A COMPLETED, AND 60% OF URGENT CARE CLIENTS ENGAGING IN REFERRAL FOR MENTAL HEALTH SERVICES; AND (4) IMPROVE OVERALL HEALTH AND REDUCE MORTALITY FOR CCBHC CLIENTS WITH 80% RECEIVING BMI SCREENING. THIS PROJECT WILL FOCUS ON ESTABLISHING FORMAL COLLABORATIONS WITH HOSPITALS, EMERGENCY DEPARTMENTS, OTHER HEALTHCARE PROVIDERS, COURTS, SCHOOLS, AND SOCIAL SERVICE AGENCIES TO PROMOTE THE LEVEL OF INTEGRATED CARE THAT IS ASSOCIATED WITH IMPROVED OUTCOMES FOR INDIVIDUALS SERVED. TOWARDS THIS GOAL, STAFF WILL ASSIST DCOS AND OTHER COLLABORATING AGENCIES IN DEVELOPING A COMPREHENSIVE SYSTEM TO RECORD AND REPORT DATA. ADDITIONALLY, TO ADDRESS CLINICAL STAFFING SHORTAGES IN BEHAVIORAL HEALTH CURRENTLY EXPERIENCED IN THE COMMUNITY AND BUILD CAPACITY FOR LONG TERM SUSTAINABILITY THE PROJECT TEAM WILL INCLUDE STAFF TO EXPAND TRAINING IN EVIDENCE-BASED PRACTICES AND COORDINATION OF STUDENT AND INTERNSHIP PLACEMENTS. THE CCBHC PROGRAM WILL ORGANIZE AN ADVISORY WORKGROUP COMPRISED OF CLIENTS AND FAMILY MEMBERS THAT WILL MEET REGULARLY TO REVIEW PROGRAM IMPLEMENTATION AND EFFECTIVENESS AND PROVIDE FEEDBACK TO HARBOR LEADERSHIP AND MEMBERS OF THE GOVERNING BOARD. POST SAMHSA GRANT AND SUCCESSFUL IMPLEMENTATION IN LUCAS COUNTY, THIS TEAM PLANS TO IMPROVE AND EXPAND ITS UTILIZATION OF CCBHC PROGRAM COMPONENTS TO OTHER OHIO COMMUNITIES SERVED BY HARBOR.

ECONOMIC DEVELOPMENT INITIATIVE, COMMUNITY PROJECT FUNDING, AND MISCELLANEOUS GRANTS

AWARD PURPOSE TO PROVIDE "PRE-RELEASE" AND "POST-RELEASE" TO SUPPORT EMPLOYMENT, TRAINING, SKILL DEVELOPMENT, AND SUCCESSFUL REENTRY INTO THE COMMUNITY. ACTIVITIES PERFORMED THE PROJECT WILL PROVIDE INMATES WITH A COMPREHENSIVE EMPLOYMENT, TRAINING, AND REENTRY EXPERIENCE. INMATES WILL WORK WITH AN EMPLOYMENT SPECIALIST ASSIGNED ACCORDING TO THE COUNTY THEY WILL BE REENTERING, ON PRERELEASE SERVICES AND GOALS. DELIVERABLES OUTCOME DATA WILL BE GATHERED AND REPORTED OUT MONTHLY TO THE TEAM AND QUARTERLY TO FUNDING SOURCE. INTENDED BENEFICIARY INMATES AT CCNO, LOCAL COMMUNITIES AND BUSINESSES. SUBRECIPIENT ACTIVITIES N/A

2/2-RARE BIPOLAR LOCI IDENTIFICATION THROUGH SYNAPTOME SEQUENCING.

RESEARCH-PGR: LIVING FOSSILS: APPLYING ADVANCES IN SINGLE MOLECULE SEQUENCING TO DECODE LARGE AND COMPLEX GENOMES OF ANCIENT PLANT LINEAGES

FIBROBLAST HETEROGENEITY IN PANCREATIC CANCER - ABSTRACT PANCREATIC DUCTAL ADENOCARCINOMA (PDA) IS CHARACTERIZED BY AN EXTENSIVE DESMOPLASTIC STROMA THAT REPRESENTS A MAJOR CHALLENGE FOR ITS EFFECTIVE TREATMENT AND IMPROVED SURVIVAL OF PATIENTS. WE SEEK TO DEFINE THE COMPOSITION AND ROLES OF CANCER-ASSOCIATED FIBROBLASTS (CAFS), THE MOST ABUNDANT CELL POPULATION IN THE PDA STROMA, AS A POTENTIAL AVENUE FOR THE DEVELOPMENT OF NEW THERAPEUTIC STRATEGIES. ALTHOUGH CAFS HAVE BEEN HISTORICALLY CONSIDERED TUMOR-PROMOTING COMPONENTS, THEIR ABLATION IN PRE-CLINICAL AND CLINICAL STUDIES HAVE LED TO MIXED OUTCOMES, INDICATING THE POORLY UNDERSTOOD COMPLEXITY OF CAFS. TO INVESTIGATE CAF BIOLOGY, WE PREVIOUSLY ESTABLISHED A PANCREATIC TUMOR ORGANOID/FIBROBLAST CO-CULTURE MODEL. IN ADDITION, WE PERFORMED SINGLE CELL RNA- SEQUENCING (SCRNA-SEQ) OF MURINE AND HUMAN PDA SPECIMENS TO CHARACTERIZE CAF COMPOSITION AT SINGLE-CELL RESOLUTION. THESE ANALYSES HAVE REVEALED THAT FIBROBLASTS ARE HETEROGENEOUS AND COMPRISED OF AT LEAST THREE DISTINCT SUBTYPES WITH UNIQUE TRANSCRIPTIONAL AND FUNCTIONAL FEATURES. MORE SO, THIS HETEROGENEITY EMPHASIZES THE NEED TO DESIGN THERAPIES THAT SELECTIVELY TARGET THE TUMOR-PROMOTING CAF POPULATIONS. ALTHOUGH OUR WORK HAS STARTED TO REVEAL THE COMPLEX HETEROGENEITY OF FIBROBLASTS IN PRIMARY OR METASTATIC PDA TISSUES, ITERATIVE DEVELOPMENTS IN SCRNA-SEQ AND ANALYSIS METHODS HAVE REVEALED FOUR ADDITIONAL CAF SUBTYPES IN PRIMARY AND METASTATIC PDA. TO COMPREHENSIVELY DEFINE THE CAF REPERTOIRE IN PRIMARY AND METASTATIC PDA, WE WILL SYSTEMATICALLY DIFFERENTIATE CAF SUBTYPES AND THEIR REGULATORY ELEMENTS USING SCRNA-SEQ, SCATAC-SEQ, MACHINE-LEARNING COMPUTATIONAL METHODS, AND IN SITU TISSUE ANALYTIC METHODS THAT DETECT RNA AND PROTEIN SPECIES, SUCH AS IMAGING MASS CYTOMETRY (AIM 1). WE HYPOTHESIZE THAT A DEEPER UNDERSTANDING OF THE DYNAMIC CAF STATES THAT OCCURS IN PRIMARY AND METASTATIC PDA WILL GUIDE THE SELECTION OF SPECIFIC THERAPEUTIC REGIMENS. TO COMPLEMENT THIS ANALYSIS, WE WILL IDENTIFY NEW CAF SUBTYPES AND STUDY THEIR DYNAMICS IN A NOVEL MURINE MODEL WITH A REVERSIBLE MUTANT KRAS ALLELE (AIM 2). FURTHERMORE, WE WILL STUDY CAF-ACTIVATING PATHWAYS BY INVESTIGATING SEVERAL GENES IMPLICATED IN STROMAL ACTIVATION THAT WERE REVEALED USING OUR RECENTLY DEVELOPED INTRADUCTAL TRANSPLANTATION MODEL OF PDA (AIM 2). THESE NEW MEDIATORS APPEAR TO HAVE ROLES IN PDA PROGRESSION, IMMUNOSUPPRESSION, AND STROMAL ACTIVATION, AND MAY REPRESENT NEW PDA THERAPEUTIC TARGETS. FINALLY, WE HAVE DEMONSTRATED DIFFERENT IMMUNOMODULATORY FUNCTIONS OF DISTINCT CAF SUBTYPES. WE WILL TEST COMBINATORIAL STRATEGIES TO TARGET DISTINCT CAF SUBTYPES IN THE PDA MICROENVIRONMENT, AND STUDY THE EFFECT OF THESE STRATEGIES ON TUMOR PROGRESSION IN A MURINE PDA MODEL (AIM 3). IN ADDITION, WE WILL ASSESS THE ROLE OF MACROPHAGE-CAF CROSSTALK IN PROMOTING AND MAINTAINING CAF IDENTIFY. OVERALL, THIS PROJECT WILL CLARIFY THE DIVERSITY OF PDA CAFS AND THE ROLE OF CANCER CELLS IN REGULATING CAF SUBTYPES. OUR RESULTS WILL PROVIDE NEW AVENUES FOR CAF-TARGETING THAT WE INTEND TO TRANSLATE TOWARDS IMPROVED THERAPIES FOR PATIENTS AFFLICTED BY THIS LETHAL DISEASE.

TOWARDS QUANTITATIVE CELL TYPE-BASED MAPPING OF THE WHOLE MOUSE BRAIN

DISSEMINATION OF MAPSEQ AND BARSEQ FOR HIGH-THROUGHPUT BRAIN MAPPING - THE GOAL OF THIS PROJECT IS TO DISSEMINATE MAPSEQ AND BARSEQ TO THE BROADER NEUROSCIENCE COMMUNITY. THESE ARE NOVEL METHODS DEVELOPED IN MY LABORATORY BASED ON HIGH-THROUGHPUT DNA SEQUENCING FOR DETERMINING NEURONAL CIRCUITRY. NEURONS TRANSMIT INFORMATION TO DISTANT BRAIN REGIONS VIA LONG-RANGE AXONAL PROJECTIONS. IN SOME CASES, FUNCTIONALLY DISTINCT POPULATIONS OF NEURONS ARE INTERMINGLED WITHIN A SMALL REGION. DISRUPTIONS OF CONNECTIVITY MAY UNDERLIE MANY NEUROPSYCHIATRIC DISORDERS INCLUDING AUTISM AND SCHIZOPHRENIA. AT PRESENT, NEUROANATOMICAL TECHNIQUES—PARTICULARLY THOSE WITH SINGLE NEURON RESOLUTION—ARE EXPENSIVE AND LABOR INTENSIVE. MAPSEQ AND BARSEQ CONVERT NEUROANATOMY INTO A PROBLEM OF DNA SEQUENCING, AND THEREBY ALLOW US TO EXPLOIT THE TREMENDOUS BREAKTHROUGHS IN NEXT- GENERATION SEQUENCING THROUGHPUT. THE DISSEMINATION OF THESE HIGH-THROUGHPUT METHODS FOR DETERMINING NEURONAL PROJECTIONS WILL HAVE IMPORTANT IMPLICATIONS FOR UNDERSTANDING NORMAL NEURONAL CIRCUITRY, AND HOW THIS CIRCUITRY IS DISRUPTED IN ANIMAL MODELS OF NEUROPSYCHIATRIC DISORDERS LIKE AUTISM AND SCHIZOPHRENIA.

GENETIC TARGETING OF CORTICAL PYRAMIDAL NEURON SUBTYPES

OP EARLY INTERVENTION SVCS W/RESPECT TO HIV DISEASE

CELL-BASED GENOMIC ANALYSIS OF MOLECULAR PATHOLOGY IN MOUSE MODELS OF RETT SYNDRO

ARREST DETERIORATION OF FORD ISLAND AVIATION CONTROL TOWER

RECEPTOR PTPS, CELL CONTRACT AND SIGNAL TRANSDUCTION

THE ROLE OF CRYPTOCHROMES IN ENVIRONMENTAL REGULATION OF GROWTH

PORT OF GRAYS HARBOR ,PORT INDUSTRIAL RD UPGRADE FROM:EAST TERMINAL WAY TO:30TH ST, HOQUIAM LEN: 1.080MI

CARES ACT: HIGHER EDUCATION EMERGENCY RELIEF FUND FOR GRAYS HARBOR COLLEGE

IMPROVE EXISTING AIRPORT

COMPUTATIONAL AND CIRCUIT MECHANISMS FOR INFORMATION TRANSMISSION IN THE BRAIN

HEALTH CENTER PROGRAM

THIS EDA ECONOMIC ADJUSTMENT ASSISTANCE TO COAL COMMUNITIES AWARD WILL HELP THE CITY OF HARBOR BEACH CONSTRUCT A HIGHER CAPACITY WATERMAIN TO SERVE THE REGIONAL WATER SYSTEM AND LARGE INDUSTRIAL USERS. FOLLOWING THE CLOSURE AND DEMOLITION OF A COAL-FIRED POWER PLANT LOCATED IN THE HEART OF HARBOR BEACH, LOCAL LEADERS RECOGNIZED THE NEED FOR SITE REDEVELOPMENT AND SUPPORTING INFRASTRUCTURE INCLUDING THE EXPANDED WATERMAIN. THE EDA-FUNDED 6,000 FEET OF 24? WATERMAIN WILL IMPROVE UPON THE DECAYING 16? WATERMAIN THAT WILL BE REMOVED AS PART OF THE PROJECT. THE EXPECTED REDEVELOPMENT OF THE COAL POWER PLANT SITE AND INCREASED WATER CAPACITY THROUGHOUT THE CITY IS EXPECTED TO CREATE AND RETAIN 285 JOBS.

WWD ALASKAN VILLAGES GRANTS - DOMESTIC WATER

DESCRIPTION:THIS AGREEMENT PROVIDES FUNDING TO THE CITY OF TWO HARBORS, MN TO IMPLEMENT ITS PROJECT TO CONVERT THE EXISTING FACILITY TO AN EXTENDED AERATION ACTIVATED SLUDGE SYSTEM AS DIRECTED IN THE 2022 CONSOLIDATED APPROPRIATIONS ACT OR AS IDENTIFIED IN AN APPROVED TECHNICAL CORRECTION IF ONE HAS BEEN APPROVED FOR THIS PROJECT.ACTIVITIES:THE ACTIVITIES TO BE PERFORMED ARE TO UTILIZE THE FUNCTIONAL PORTIONS OF THE EXISTING FACILITY, INCLUDING THE EQUALIZATION TANK, PRETREATMENT FACILITY, EQUALIZATION CHLORINE CONTACT TANK, AND TERTIARY FILTERS. THE PRETREATMENT BUILDING WILL INCLUDE THE FOLLOWING REHABILITATIONS/REPLACEMENTS: ROOFING, HVAC SYSTEM, RAW WATER PUMPS, GRIT CLASSIFIER. THE PROJECT CONSTRUCTION WILL INCLUDE EXTENDED AERATION ACTIVATED SLUDGE AERATION BASIN (VOLUME OF 1.2 MILLION GALLONS); TWO FINAL CLARIFIERS 75 FEET IN DIAMETER PROVIDING REDUNDANT CAPACITY OF 4.0 MGD, PROVIDING TREATMENT FOR THE MAX FLOW OF 2.6 MGD AND BACKWASH RETURN FLOW OF 1.4 MGD; FILTER FEED PUMPS UPSIDE TO HANDLE BACKWASH WASTE FLOW OF 1.4 MGD; AERATED BIOSOLIDS HOLDING TANK WITH 365 DAYS OF STORAGE, CONSTRUCTED WITH A VOLUME OF 2.6 MG. THE PROJECT IS DESIGNED TO ACCOMMODATE THE FOLLOWING VALUES: 1,948 LBS/DAY CARBONACEOUS BIOCHEMICAL OXYGEN DEMAND (CBOD) LOADING; MINIMUM 0.500 MILLION GALLONS PER DAY (MGD) FLOW; 1,180 LBS/DAY TOTAL SUSPENDED SOLIDS (TSS) LOADING. A DRIVEWAY TO THE ADDITIONAL FACILITIES WILL BE CONSTRUCTED. A CONCRETE WALL WILL BE CONSTRUCTED AROUND THE WWTF FACILITY. EROSION PROTECTION AND TURF RESTORATION WILL BE A PART OF CONSTRUCTION.SUBRECIPIENT:NO SUBAWARDS ARE INCLUDED IN THIS ASSISTANCE AGREEMENT.OUTCOMES:THE ANTICIPATED DELIVERABLE IS A MORE RELIABLE WASTEWATER TREATMENT FACILITY WITH PROPER DESIGN CONDITIONS WHICH WILL: * REDUCE THE POSSIBILITY OF A PLANT BYPASS * IMPROVES THE WATER TREATMENT PROCESS FOR EFFLUENT ENTERING LAKE SUPERIOR * REDUCE IMPACT ON RECEIVING WATERS * TREAT AND SAFEGUARD THE LOCAL COMMUNITY AGAINST CONTAMINANTS THIS IS EXPECTED TO LEAD TO: * SAFETY FOR THOSE USING LAKE SUPERIOR FOR RECREATIONAL PURPOSES * LONGEVITY FOR CONTINUED PUBLIC USE AS WELL AS HABITAT AND BIODIVERSITY IMPROVEMENTS * MEET EFFLUENT LIMITS TO PROTECT RECEIVING STREAMS * IMPROVED AWARENESS AND UNDERSTANDING OF THE PROJECT PURPOSE AND TIMELINE, THE ABILITY TO PROVIDE COMMENTS TO INFLUENCE DESIGN AND DIRECTIONS THE INTENDED BENEFICIARIES ARE THE LOCAL COMMUNITY, PUBLIC, AND BUSINESSES IN THE CITY OF TWO HARBORS.

GENE DISCOVERY IN THE CEREALS

CSHL WATSON SCHOOL OF BIOLOGICAL SCIENCES

COMPUTATIONAL ANALYSIS OF COMPLEX GENETIC INTERACTIONS

VA IS PROVIDING PER DIEM FUNDING TO ASSIST WITH THE OPERATIONAL COSTS ASSOCIATED WITH TRANSITIONAL HOUSING BEDS FOR HOMELESS VETERANS.

MOLECULAR AND CELLULAR MECHANISMS GOVERNING INTERNEURON DEVELOPMENT AND CONNECTIVITY

PURPOSE: EXPAND APRON. THIS GRANT IS FUNDED BY THE AMERICAN RESCUE PLAN ACT OF 2021 TO INCREASE THE FEDERAL SHARE TO 100 PERCENT FOR THE AIRPORT IMPROVEMENT PROGRAM (AIP). ACTIVITIES TO BE PERFORMED/EXPECTED OUTCOMES: THIS PROJECT EXPANDS THE EXISTING NORTH APRON AN ADDITIONAL 15,530 SQUARE YARDS TO ACCOMMODATE INCREASED USE OF THE GENERAL AVIATION FACILITIES. THIS IS THE FINAL PHASE OF THE PROJECT, WHICH CONSISTS OF CONSTRUCTION OF 7,000 SQUARE YARDS OF PAVEMENT. INTENDED BENEFICIARY: THIS GRANT WILL PROVIDE FEDERAL FUNDING FOR AIRPORTS ASSOCIATED WITH BAY ST. LOUIS, MISSISSIPPI.

HIGH-THROUGHPUT APPROACHES TO LOCAL AND LONG-RANGE SYNAPTIC CONNECTIVITY

AWARD PURPOSE THE PROJECT INCLUDES THE PROCUREMENT, DELIVERY, AND ASSEMBLY OF CARGO TRANSLOADING EQUIPMENT TO INCLUDE A MINIMAL 200 TON CAPACITY CRANE AND A MINIMAL 25 TON CAPACITY FORKLIFT AND RELATED CARGO HANDLING ATTACHMENTS. PROCURING MODERN AND EFFICIENT CARGO TRANSLOADING EQUIPMENT WILL PROVIDE THE PORT WITH THE CAPACITY TO BRING IN ADDITIONAL TENANTS TO UNLOAD CARGO SAFELY AND EFFICIENTLY. ACTIVITIES TO BE PERFORMED THE PROJECT INCLUDES THE FOLLOWING THREE COMPONENTS COMPONENT 1 PROCUREMENT DELIVERY AND ASSEMBLY OF A MINIMAL 200 TON CRANE. COMPONENT 2 PROCUREMENT DELIVERY AND ASSEMBLY OF A MINIMAL 25 TON FORKLIFT. COMPONENT 3 PROCUREMENT DELIVERY AND ASSEMBLY OF RELATED CARGO HANDLING ATTACHMENTS. DELIVERABLES EXPECTED OUTCOMES FROM PAGE 9 SCHEDULE G OF THE GRANT AGREEMENT MEASURE FREIGHT MOVEMENTS. CATEGORY AND DESCRIPTION ECONOMIC COMPETITIVENESS CALCULATE THE AMOUNT OF UNITIZED FREIGHT BY TONNAGE/VOLUME THAT WILL BE TRANSPORTED ON THE MARINE HIGHWAY SERVICE ON THE DESIGNATED MARINE HIGHWAY ROUTE TEUS METRIC TONS OR CUBIC BOARD METER CBM MOVEMENTS. QUARTERLY. MEASURE HIGHWAY VEHICLE MILES TRAVELED VMT AVOIDED. CATEGORY AND DESCRIPTION ECONOMIC COMPETITIVENESS CALCULATE THE VMT BY OBTAINING THE ALTERNATIVE ROAD MILES AVOIDED BY USING THE DESIGNATED MARINE HIGHWAY ROUTE. MEASUREMENT FREQUENCY. MEASURE QUARTERLY. FREQUENCY CATEGORY AND DESCRIPTION CARGO LIFTS MEASUREMENT ECONOMIC COMPETITIVENESS CALCULATE THE COUNT OF UNITIZED FREIGHT LIFTS USING CARGO HANDLING EQUIPMENT IN THE PROJECT STUDY AREA. FREQUENCY QUARTERLY. INTENDED BENEFICIARY MORGAN CITY HARBOR AND TERMINAL DISTRICT. SUBRECIPIENT ACTIVITIES NONE.

TRANSCRIPTIONAL NETWORKS GOVERNING A. FUMIGATUS VIRULENCE - ABSTRACT INVASIVE INFECTIONS DUE TO ASPERGILLUS FUMIGATUS ARE INCREASING AND ARE STILL ASSOCIATED WITH UNACCEPTABLY HIGH MORTALITY, EVEN WITH NEW THERAPIES. OUR UNDERSTANDING OF A. FUMIGATUS INFECTION BIOLOGY IS LIMITED. AMONG 10,180 PREDICTED GENES IN THE A. FUMIGATUS GENOME, OVER 95% ARE UNCHARACTERIZED, AND FEWER THAN 100 GENES HAVE DEMONSTRATED ROLES IN VIRULENCE. IT IS CRITICAL TO IDENTIFY GENES THAT GOVERN VIRULENCE AND THE PATHWAYS IN WHICH THEY ACT BECAUSE THEY CAN POINT TO HIGH PRIORITY TARGETS FOR THERAPEUTIC AND DIAGNOSTIC DEVELOPMENT. WE HAVE IDENTIFIED A TRANSCRIPTIONAL REGULATOR IN A. FUMIGATUS, WRPA, THAT SHARES LIMITED HOMOLOGY WITH CANDIDA ALBICANS WOR1 AND HISTOPLASMA CAPSULATUM RYP1. OUR PRELIMINARY DATA INDICATE THAT WRPA GOVERNS THE CAPACITY OF A. FUMIGATUS TO WITHSTAND MACROPHAGE KILLING, GROW UNDER HYPOXIC CONDITIONS, AND INVADE AND DAMAGE PULMONARY CELLS IN VITRO. WRPA DELETION MUTANTS HAVE HIGHLY ATTENUATED VIRULENCE IN THE MOUSE MODEL OF INVASIVE ASPERGILLOSIS. USING RNA-SEQ, WE FOUND THAT WRPA GOVERNS THE EXPRESSION OF ~15% OF GENES IN THE A. FUMIGATUS GENOME, INCLUDING MULTIPLE TRANSCRIPTION FACTOR GENES. OUR PREMISE IS THAT THE WRPA IS A MASTER REGULATOR THAT GOVERNS HOST CELL INTERACTIONS AND VIRULENCE. IN SUPPORT OF THIS PREMISE, OUR INITIAL INVESTIGATIONS OF THE WRPA REGULON HAVE ALREADY REVEALED NOVEL PATHOGENICITY-RELATED FUNCTIONS OF THREE WRPA-DEPENDENT TRANSCRIPTION FACTORS, SRBB, FCR1, AND NDT80. OUR GOAL IS TO CHARACTERIZE THE WRPA REGULON IN A. FUMIGATUS AND TO IDENTIFY DOWNSTREAM EFFECTOR GENES WHOSE PRODUCTS MEDIATE PATHOGENICITY BY: 1) IDENTIFYING THE TRANSCRIPTION FACTORS THAT ARE DIRECTLY REGULATED BY WRPA AND DETERMINING THEIR ROLES IN PATHOGENICITY; 2) ANALYZING SELECTED WRPA- DEPENDENT TRANSCRIPTION FACTORS AND IDENTIFYING THEIR DOWNSTREAM TARGET GENES; AND 3) DETERMINING THE FUNCTION OF EFFECTOR GENES CONTROLLED BY THE WRPA REGULON AND INVESTIGATING THEIR ROLES IN VIRULENCE. THE RESULTS OF THE EXPERIMENTS DESCRIBED IN THIS PROPOSAL WILL ENABLE US TO CHARACTERIZE A KEY TRANSCRIPTIONAL REGULATOR THAT GOVERNS A. FUMIGATUS PATHOGENICITY AND THEN USE THIS INFORMATION TO IDENTIFY DOWNSTREAM EFFECTOR GENES, THE PRODUCTS OF WHICH MEDIATE HOST CELL INTERACTIONS AND VIRULENCE. THE RESULTS OF THIS WORK WILL NOT ONLY PROVIDE FOUNDATIONAL UNDERSTANDING OF A. FUMIGATUS VIRULENCE MECHANISMS, BUT ALSO HOLD PROMISE TO IDENTIFY NEW DIAGNOSTIC, THERAPEUTIC, AND VACCINE TARGETS.

TAS::89 0321::TAS LONG ISLAND BIOFUELS ALLIANCE

RNAI AS A ROUTINE ROUTE TOWARD BREAST CANCER THERAPY

TYPE I IFN SIGNALING DURING LUNG DEVELOPMENT IN DOWN SYNDROME - PROJECT SUMMARY/ABSTRACT DOWN SYNDROME (DS), ALSO REFERRED TO AS TRISOMY 21, IS THE MOST COMMON HUMAN CHROMOSOMAL ANOMALY, AFFECTING 1 IN 700 LIVE BIRTHS. ALTHOUGH DS CAN AFFECT MANY ORGAN SYSTEMS, LUNG AND HEART DISEASE ARE THE LEADING CAUSES OF MORBIDITY AND MORTALITY. SEVERAL CONGENITAL LUNG ANOMALIES ARE REPORTED IN INDIVIDUALS WITH DS INCLUDING AIRWAY BRANCHING DEFECTS, WITH A 25% DECREASE IN THE NUMBER OF BRANCHES AND REDUCED UPPER AIRWAY MUSCLE TONE WITH DYSPHAGIA AND/OR BRONCHOMALACIA. THESE COMPLICATIONS REMAIN CONSTANT INTO ADULTHOOD, AS OPPOSED TO BECOMING EXACERBATED, AND ARE HENCE LIKELY DUE TO DEVELOPMENTAL INSUFFICIENCY. WHILE ABNORMAL PULMONARY STRUCTURE AND FUNCTION IN PEDIATRIC AND ADULT DS SUBJECTS HAS BEEN DESCRIBED, THERE IS LIMITED DATA DEFINING THE ONTOGENY OF THESE ABNORMALITIES. WE POSTULATED THAT SOME DEVELOPMENTAL DIFFERENCES COULD INITIATE PRENATALLY. PRELIMINARY DATA DEVELOPED FOR THIS APPLICATION SHOWS THAT DS FETAL LUNGS, STARTING AS EARLY AS 16 WEEKS GESTATION, PRESENT WITH PRONOUNCED DILATATION OF TERMINAL AIRWAYS/ACINAR TUBULES, DILATED LYMPHATICS AND MUSCULARIZED ARTERIES. IN ADDITION, WE FIND INCREASED LUNG EXPRESSION OF TYPE I IFN SIGNALING TARGET GENES SUCH AS MX1 AND IFI27 IN DS COMPARED TO NON-DS FETAL LUNGS. IFN SIGNALING PLAYS A CRITICAL ROLE IN CELL DIFFERENTIATION, PROLIFERATION, APOPTOSIS, AND ECM PRODUCTION, IMPORTANT EVENTS FOR LUNG DEVELOPMENT. FINALLY, OUR PRELIMINARY DATA SHOW THAT DS LUNGS EXHIBIT ALTERED EXPRESSION OF ECM AFFILIATED PROTEINS, REGULATORS, AND SECRETED FACTORS (FN1, COL6, ETC.). THEREFORE, WE HYPOTHESIZE THAT LUNG DEFECTS IN DS CAN INITIATE DURING FETAL DEVELOPMENT, AND THAT IFN-DEPENDENT CHANGES IN CELL PROLIFERATION, DIFFERENTIATION AND ECM PRODUCTION CONTRIBUTE TO THESE DEFECTS. TO TEST THIS HYPOTHESIS, WE WILL 1) TEST THE HYPOTHESIS THAT MORPHOLOGICAL, CELLULAR AND MOLECULAR ABNORMALITIES ARE INITIATED DURING THE LATE PSEUDOGLANDULAR/EARLY CANALICULAR STAGES OF FETAL DEVELOPMENT IN DS LUNGS USING HISTOPATHOLOGICAL ANALYSES AND SINGLE CELL SEQUENCING, 2) TEST THE HYPOTHESIS THAT EXCESSIVE TYPE I IFN SIGNALING DISRUPTS CELL DIFFERENTIATION AND AIRWAY BRANCHING DURING FETAL LUNG DEVELOPMENT IN DS, AND 3) TEST THE HYPOTHESIS THAT EXCESSIVE IFN SIGNALING DISRUPTS ECM PRODUCTION DURING FETAL LUNG DEVELOPMENT IN DS. FOR AIMS 2 AND 3, WE WILL USE OUR PUBLISHED FETAL LUNG EXPLANTS CULTURE MODEL AS WELL AS EPITHELIAL ORGANOID CULTURES ALONE OR CO-CULTURED WITH MESENCHYMAL CELLS TO TEST THE EFFECT OF GAIN AND LOSS OF FUNCTION OF TYPE I IFN SIGNALING ON CELL DIFFERENTIATION AND ECM PRODUCTION. THESE STUDIES HAVE THE PROMISE TO IMPROVE OUR UNDERSTANDING OF THE KEY MOLECULAR AND CELLULAR DIFFERENCES, AND THE MECHANISMS CONTROLLING BRANCHING DEFECTS IN DS DEVELOPING LUNGS. THE INNOVATIVE ASPECTS OF THIS WORK ARE LIKELY TO HAVE GREAT OVERALL IMPACT AND FACILITATE THE TRANSLATIONAL POTENTIAL FOR THERAPIES FOR DS INDIVIDUALS, AS WELL AS OTHER LUNG CONGENITAL DEFECTS DEMONSTRATING HYPOPLASTIC LUNGS.

THE ROLE OF CHD5 IN CHROMATIN-MEDIATED REGULATION OF NEURAL STEM CELLS AND GLIOMA

CHARACTERIZING SUB-CELLULAR COMPARTMENTS IN MAIZE USING FLUORESCENT PROTEIN TAGGED LINES

DOMESTIC WATER GRANTS - REGULAR

PURPOSE: EXPAND APRON. THIS GRANT IS FUNDED BY THE CORONAVIRUS AID, RELIEF, AND ECONOMIC SECURITY ACT TO INCREASE THE FEDERAL SHARE TO 100 PERCENT FOR THE AIRPORT IMPROVEMENT PROGRAM (AIP). ACTIVITIES TO BE PERFORMED/EXPECTED OUTCOMES: THIS PROJECT EXPANDS THE EXISTING NORTH APRON TO 40,850 SQUARE YARDS TO ACCOMMODATE INCREASED USE OF THE GENERAL AVIATION FACILITIES. THIS GRANT FUNDS THE FIRST PHASE, WHICH CONSISTS OF THE CONSTRUCTION OF 8,350 SQUARE YARDS OF PAVEMENT. INTENDED BENEFICIARY: THIS GRANT WILL PROVIDE FEDERAL FUNDING FOR AIRPORTS ASSOCIATED WITH BAY ST. LOUIS, MISSISSIPPI.

MECHANISMS AND TREATMENT OF PTEN MUTANT PROSTATE TUMORIGENESIS

ELECTROPHYSIOLOGICAL ANALYSIS OF OLFACTORY REPRESENTATIONS IN DROSOPHILA

STAPHYLOCOCCAL ADAPTATIONS TO PLATELET MICROBICIDAL PROTEIN

VA IS PROVIDING PER DIEM FUNDING TO ASSIST WITH THE OPERATIONAL COSTS ASSOCIATED WITH TRANSITIONAL HOUSING BEDS FOR HOMELESS VETERANS.

VA IS PROVIDING PER DIEM FUNDING TO ASSIST WITH THE OPERATIONAL COSTS ASSOCIATED WITH TRANSITIONAL HOUSING BEDS FOR HOMELESS VETERANS.

ECONOMIC DEVELOPMENT INITIATIVE, COMMUNITY PROJECT FUNDING, AND MISCELLANEOUS GRANTS

AWARD PURPOSE THE PROJECT WILL MODERNIZE THE FACILITYS CARGO HANDLING INFRASTRUCTURE BY PAVING APPROXIMATELY SEVEN ACRES OF THE UNDERUTILIZED ROCK SURFACED AREA AS WELL AS PROVIDE CONNECTIVITY TO ADJACENT STORAGE TRANSIT SHEDS AND RAILROADS TO ACCOMMODATE MULTIMODAL TRANSLOADING OPTIONS FOR CARGO. THE NEW FACILITY WILL IMPROVE DRAINAGE AND BE CONSTRUCTED FOR MULTIPURPOSE USE TO ALLOW THE SITE TO BE UTILIZED FOR VARIOUS IMPORTED AND EXPORTED CARGO TYPES. ACTIVITIES TO BE PERFORMED THE PROJECT WILL BE COMPLETED AS TWO COMPONENTS CARGO YARD IMPROVEMENTS PAVE APPROXIMATELY SEVEN ACRES OF CARGO STORAGE YARD WITH RELATED DRAINAGE IMPROVEMENTS. RAIL EXTENSION: CONSTRUCT APPROXIMATELY 200 LINEAR FEET OF AT GRADE RAIL EXTENSION. DELIVERABLES EXPECTED OUTCOMES ON PAGE 10 OF THE GRANT AGREEMENT SCHEDULE G. MEASURE CARGO VOLUME TOTAL TONS CARGO MOVED PER YEAR TEUS AND OR SHORT TONS. CATEGORY AND DESCRIPTION ECONOMIC COMPETITIVENESS AND OPPORTUNITY CARGO VOLUME MEASURES THE MOVEMENT OF FREIGHT THROUGH THE PROJECT STUDY AREA. REPORT THE TOTAL CARGO VOLUME AND THE VOLUME DISAGGREGATED BY TYPE OF FREIGHT I E CONTAINERS IN TEU AND BULK IN TONS OR TYPE OF INTERMODAL TRANSPORT TRUCK OR RAIL. MEASURE VESSEL CALLS TOTAL VESSEL CALLS PER YEAR. CATEGORY AND DESCRIPTION ECONOMIC COMPETITIVENESS AND OPPORTUNITY MEASURES THE NUMBER OF VESSELS CALLING TO THE PROJECT STUDY AREA. MUST BE REPORTED IN TOTAL AND DISAGGREGATED BY ANY OF THE FOLLOWING WHERE APPLICABLE: VESSEL TYPE E G CONTAINER BULK RO RO LNG FREIGHT CAPACITY VESSEL LENGTH, OR OTHER. MEASUREMENT FREQUENCY QUARTERLY. INTENDED BENEFICIARY LAKE CHARLES HARBOR AND TERMINAL DISTRICT. SUBRECIPIENT ACTIVITIES NONE.

EPIGENETIC DYNAMICS OF DEVELOPING GERM CELLS AND EARLY EMBRYOS

CORONARY ARTERY CALCIUM, AORTIC CALCIFICATION AND DENSITY IN MESA

ULTRA-EARLY SURGERY FOR ACUTE SPINAL CORD INJURY: A PROSPECTIVE TRIAL OF TIMING OF SURGICAL DECOMPRESSION

C. ALBICANS INVASION AND PROLIFERATION DURING ORAL INFECTION

PORT SECURITY GRANT PROGRAM (ARRA)

NRF2 REGULATION OF DUCTAL PANCREATIC CANCER ETIOLOGY AND TREATMENT RESPONSE

THE MOLECULAR BASIS OF PREGNANCY-ASSOCIATED PROTECTION FROM BREAST CANCER

TARGETING ABERRANT ENHANCER LANDSCAPES IN PANCREATIC CANCER

NEURODEVELOPMENTAL DISORDER-ASSOCIATED RHO REGULATORS IN NEOCORTICAL DEVELOPMENT

COMBINATION WATER & WASTE DISPOSAL GRANTS - REGULAR

DEVELOPMENT OF PAN-GENOMIC & COMPUTATIONAL RESOURCES FOR AGRICULTURE

NEUROIMMUNOLOGICAL INSIGHTS INTO BRAIN DEVELOPMENT AND DYSFUNCTION: AN INTEGRATIVE APPROACH FOCUSED ON MICROGLIAL DYNAMICS - PROJECT SUMMARY: NEURODEVELOPMENTAL DISORDERS SUCH AS AUTISM AND INTELLECTUAL DISABILITY AFFECT 14% OF AMERICAN CHILDREN AND OVER 50 MILLION PEOPLE WORLD-WIDE. PHARMACOLOGICAL THERAPIES FOR TREATING THESE DISORDERS ARE VIRTUALLY NON- EXISTENT IN LARGE PART DUE TO OUR LIMITED UNDERSTANDING OF THE NEURAL CIRCUIT WIRING DEFICITS THAT UNDERLIE THEIR DIVERSE AND NUANCED SYMPTOMS. WHILE IT HAS BEEN WELL-ESTABLISHED THAT NEURODEVELOPMENTAL DISORDERS EMERGE THROUGH A COMPLEX INTERPLAY OF GENETICS (NATURE) AND ENVIRONMENTAL FACTORS (NURTURE), THE MAJORITY OF RESEARCH INTO THESE CONDITIONS HAS FOCUSED ON SPECIFIC GENETIC MUTATIONS UNDERLYING RARE SUBSETS OF DISORDERS, LEAVING THE ENVIRONMENTAL FACTORS THAT AFFECT A MUCH WIDER ARRAY OF THESE CONDITIONS POORLY UNDERSTOOD. TO ALLEVIATE THE SUFFERING OF AS MANY INDIVIDUALS AS POSSIBLE, WE WILL ADDRESS THIS MAJOR GAP IN KNOWLEDGE BY DEFINING THE ENVIRONMENTAL FACTORS THAT EXACERBATE NEURODEVELOPMENTAL DYSFUNCTION. OUR APPROACH IS BASED UPON MOUNTING CLINICAL AND EXPERIMENTAL EVIDENCE THAT IMPAIRMENTS IN INTERACTIONS BETWEEN THE IMMUNE SYSTEM AND THE BRAIN DRIVE NEUROPATHOLOGY, AN UNEXPECTED FINDING GIVEN THAT THE IMMUNE AND NERVOUS SYSTEMS WERE CLASSICALLY CONSIDERED TO BE DISTINCT BIOLOGICAL DOMAINS. THE CENTRAL HYPOTHESIS UNDERLYING THE PROPOSED WORK IS THAT A SPECIALIZED CLASS OF BRAIN-RESIDENT IMMUNE CELLS CALLED MICROGLIA PLAY A CRITICAL ROLE IN COORDINATING A LATE STAGE OF CIRCUIT DEVELOPMENT THAT IS THOUGHT TO GO AWRY IN NEUROPATHOLOGICAL STATES: THE SENSORY EXPERIENCE-DEPENDENT REFINEMENT OF DEVELOPING SYNAPSES. IF SO, THE DISRUPTION OF MICROGLIAL FUNCTION IN EXPERIENCE-DEPENDENT REFINEMENT MAY BE A CORE FEATURE OF NEURODEVELOPMENTAL DISORDERS RENDERING MICROGLIA A PROMISING TARGET FOR TREATMENT, PARTICULARLY BECAUSE EXPERIENCE-DEPENDENT REFINEMENT REPRESENTS A STATE OF HEIGHTENED PLASTICITY WHEN THE BRAIN MAY BE PARTICULARLY RECEPTIVE TO THERAPEUTIC INTERVENTION. HARNESSING THE UNIQUE ADVANTAGES OF THE VISUAL CIRCUITRY OF THE MOUSE AS A MODEL SYSTEM, WE WILL MERGE TWO-PHOTON IMAGING OF MICROGLIA AND SYNAPSES IN THE BRAINS OF LIVE, AWAKE MICE WITH SINGLE-CELL GENOMICS AND CRISPR-BASED SCREENS TO DEFINE THE ROLES OF MICROGLIA IN EXPERIENCE-DEPENDENT REFINEMENT. IN PARALLEL, WE WILL UTILIZE THE MATERNAL IMMUNE ACTIVATION MOUSE MODEL TO IDENTIFY SPECIFIC MECHANISMS OF REFINEMENT THAT ARE LIKELY TO BE DISRUPTED IN NEURODEVELOPMENTAL DISORDERS. GIVEN THAT MALES ARE AT LEAST THREE TIMES MORE LIKELY TO HAVE AUTISM THAN FEMALES, OUR WORK WILL ALSO ASSESS HOW THESE MICROGLIAL PROCESSES DIFFER DEPENDING UPON SEX. IN THE COURSE OF THIS WORK, WE WILL DEVELOP MUCH-NEEDED VIRAL TOOLS FOR STUDYING MICROGLIA IN THE BRAIN. OUR OVERARCHING GOAL IS TO LAY THE FOUNDATION FOR THE DEVELOPMENT OF NEW PHARMACOLOGICAL STRATEGIES FOR TREATING NEURODEVELOPMENTAL DISORDERS BY RESTORING HEALTHY MICROGLIAL FUNCTION DURING POSTNATAL BRAIN DEVELOPMENT. IN ADDITION TO THE HIGH-RISK/HIGH-REWARD NATURE OF THE PROPOSAL, THIS PROJECT IS PARTICULARLY WELL-SUITED FOR THE NIH DIRECTOR’S NEW INNOVATOR AWARD BASED UPON CONCEPTUAL NOVELTY, PROMISE TO ACHIEVE KEY TECHNOLOGICAL ADVANCES, AND POTENTIAL TO ALLEVIATE A MAJOR HEALTHCARE BURDEN AFFECTING THE UNITED STATES AND THE WORLD.

SYNPLA: A SCALEABLE METHOD FOR MONITORING CIRCUIT-SPECIFIC LEARNING-INDUCED CHANGES IN SYNAPTIC STRENGTH

GENES AND NETWORKS REGULATING SHOOT MATURATION AND FLOWER PRODUCTION IN TOMATO AND RELATED NIGHTSHADES

IDENTIFICATION AND CHARACTERIZATION OF GENOMIC FEATURES AFFECTING SURVIVAL DURATION IN CANCER

TRANSPOSONS, RNA INTERFERENCE AND HETEROCHROMATIN

PURPOSE: RECONSTRUCT TAXILANE; RECONSTRUCT APRON. ACTIVITIES TO BE PERFORMED/EXPECTED OUTCOMES: THIS PROJECT RECONSTRUCTS 2,100 FEET OF THE EXISTING TAXILANE PAVEMENT THAT HAS REACHED THE END OF ITS USEFUL LIFE. THIS PROJECT RECONSTRUCTS 8,785 SQUARE YARDS OF THE EXISTING GENERAL AVIATION APRON PAVEMENT THAT HAS REACHED THE END OF ITS USEFUL LIFE. THIS GRANT FUNDS PHASE 2, WHICH CONSISTS OF CONSTRUCTION. INTENDED BENEFICIARY: THIS GRANT WILL PROVIDE FEDERAL FUNDING FOR AIRPORTS ASSOCIATED WITH HOQUIAM, WASHINGTON.

STRENGTHENING INSTITUTIONS - HISPANIC SERVING INSTITUTIONS

DEEP SEQUENCING OF AUTISM CANDIDATE GENES IN 2000 FAMILIES FROM THE SIMONS SIMPLE

SOCIAL ODOR MODULATION OF AUDITORY CORTEX VIA THE BASAL AMYGDALA - PROJECT SUMMARY OLFACTION IS UNIQUE AMONG THE SENSES FOR ITS DIRECT AND INTIMATE CONNECTIONS TO THE LIMBIC SYSTEM. THIS MAY EXPLAIN THE WIDESPREAD SUBJECTIVE EXPERIENCE THAT ODORS CAN TRIGGER POWERFUL AFFECTIVE RESPONSES, ESPECIALLY ODORS FROM SOCIAL PARTNERS. THIS IS A FUNDAMENTAL MODE OF SOCIAL COMMUNICATION IN MANY SPECIES, INCLUDING HUMANS, YET THE NEURAL CIRCUITS THAT LINK ODOR-EVOKED EMOTIONAL STATES TO CHANGES IN PERCEPTION AND SOCIAL INTERACTION REMAIN UNCLEAR. OUR GOAL IS TO DETERMINE HOW ODOR CUES FROM OFFSPRING INFLUENCE NEURAL AND BEHAVIORAL RESPONSES TO INFANT VOCALIZATIONS IN MICE. WE WILL USE A ROBUST AND ESSENTIAL MATERNAL BEHAVIOR (PUP RETRIEVAL) THAT REQUIRES BOTH OLFACTION AND AUDITION TO ASK: IF AND UNDER WHAT CONDITIONS DOES RETRIEVAL ENGAGE DIRECT CROSS TALK BETWEEN THE TWO MODALITIES? AND, WHAT IS THE FUNCTIONAL SIGNIFICANCE OF THIS CROSS TALK? ONE IMPORTANT ASPECT OF MATERNAL CARE IN MICE IS THE NEED TO RETRIEVE THEIR PUPS WHEN THEY ARE AWAY FROM THE NEST AND EMITTING ULTRASONIC DISTRESS VOCALIZATIONS (USVS). FIRST TIME MOTHERS AND NULLIPAROUS FEMALES (‘SURROGATES’) HOUSED WITH A DAM AND HER LITTER RAPIDLY LEARN TO RECOGNIZE THESE CALLS AND RETURN THE YOUNG TO THE NEST. THERE ARE CONTEMPORANEOUS CHANGES IN NEURAL RESPONSES TO USVS IN THE AUDITORY CORTEX. DIRECT INTERACTION WITH PUPS IS HIGHLY REWARDING, SUGGESTING THAT SENSORY EXPERIENCE WITH OFFSPRING MAY BE A CRUCIAL TRIGGER FOR NEURAL AND BEHAVIORAL PLASTICITY. ACCORDINGLY, BOTH THE SMELL OF PUPS AND THE SOUND OF THEIR VOCALIZATIONS ARE REQUIRED FOR PERFORMANCE OF PUP RETRIEVAL. INDEED, PREVIOUS WORK SHOWED THAT PUP ODOR MODULATES NEURONAL RESPONSES TO USVS IN THE AUDITORY CORTEX OF MATERNALLY-EXPERIENCED FEMALES. OUR PRELIMINARY DATA SUGGEST THAT PUP ODOR MAY INFLUENCE RESPONSES TO USVS VIA A PATHWAY TO THE AUDITORY CORTEX (AC) FROM THE BASAL AMYGDALA (BA), A PART OF THE BRAIN THAT HAS BEEN LINKED TO MATERNAL BEHAVIOR, AND TO MOTIVATED BEHAVIOR BROADLY. THE FACT THAT THE PROJECTION TO THE AC ARISES FROM THE BA, A STRUCTURE CRITICAL FOR MOTIVATED BEHAVIOR, RAISES THE POSSIBILITY THAT THE ODOR SIGNAL CONVEYED TO THE AC ENCODES AFFECTIVE STATE INFORMATION SUCH AS SALIENCE OR REWARD. WE HYPOTHESIZE THAT THE BA IS A CONDUIT FOR PUP ODORS TO TRIGGER AFFECTIVE STATES THAT DYNAMICALLY MODULATE THE NEURAL REPRESENTATION AND SALIENCE OF USVS. HERE, WE PROPOSE TO TEST THIS HYPOTHESIS BY COMBINING A NOVEL STRUCTURED RETRIEVAL TASK, SPATIOTEMPORALLY CONTROLLED EXPOSURE TO PUP ODOR, AND NEURONAL RECORDINGS IN FREELY BEHAVING MICE. WE WILL IDENTIFY THE TEMPORAL STRUCTURE AND BEHAVIORAL DETERMINANTS OF BAACN ACTIVITY DURING RETRIEVAL (AIM 1). WE WILL DETERMINE THE RELATIONSHIP BETWEEN BAACN FIRING AND AUDITORY ACTIVITY (AIM 2). FINALLY, WE WILL TEST THE NECESSITY OF BAACN ACTIVITY DURING DISTINCT BEHAVIORAL COMPONENTS OF PUP RETRIEVAL (AIM 3).

ENDOTHELIAL INVASION BY YEAST-PHASE CANDIDA

2/2-TREATMENT OF SUICIDAL AND SELF-INJURIOUS ADOLESCENTS WITH EMOTIONAL DYSREGULA

HIGH THROUGHPUT MAPPING OF NEURONAL CIRCUITRY USING DNA SEQUENCING

THE SYNAPTIC CIRCUITRY OF THE LATERAL HABENULA AND BEHAVIORAL DEPRESSION

METASTASIS OF PTEN MUTANT PROSTATE CANCER - WITH AN ESTIMATED 190,000 NEW DIAGNOSES IN 2020, PROSTATE CANCER (PC) IS THE SECOND MOST FREQUENT TUMOR DIAGNOSED IN MEN AND THE SECOND LEADING CAUSE OF MALE CANCER DEATHS IN AMERICA. APPROXIMATELY ONE IN THREE MEN OVER THE AGE OF 50 SHOWS HISTOLOGICAL EVIDENCE OF THIS TUMOR, HOWEVER ONLY ONE IN TEN WILL BE DIAGNOSED WITH CLINICALLY SIGNICANT PC. THERAPEUTIC OPTIONS FOR LOCALIZED PC ARE EFFECTIVE, HOWEVER, METASTATIC PC IS A YET INCURABLE DISEASE BECAUSE STANDARD OF CARE ANTI-ANDROGEN THERAPY INVARIABLY RESULTS IN INCURABLE DISEASE RELAPSE. PTEN-TP53 LOSS IS A MOST SIGNICANT EVENT OF HUMAN LETHAL METASTATIC PC AS SUMMARIZED BY THE PCF/SU2C INTERNATIONAL PROSTATE CANCER DREAM TEAM (ARMENIA ET AL., 2018) AND CONRMED BY TWO DECADES OF FUNCTIONAL PC MODELING IN MOUSE. THE CENTRAL GOAL OF THIS PROJECT IS TO UNDERSTAND WHAT CAUSES PTEN-MUTANT INDOLENT PROSTATE CANCER (PC) TO METASTASIZE TO DIFFERENT PARTS OF THE BODY AND KILL THE PATIENT. WHILE THE PCF/SU2C REPORT SIGNICANT ASSOCIATION OF PTEN LOSS WITH LOSS OF TP53, THE DENITION OF FURTHER GENES THAT ARE SIGNICANTLY CO-MUTATED WITH PTEN HAS REMAINED A PROBLEM. IMPORTANTLY, SUCH GENES COULD POINT TO PATHWAYS AND PRINCIPLES THAT DRIVE METASTASIS AND/ OR THERAPY RESISTANCE. WE AIM TO SOLVE THIS PROBLEM BY COMBINING SINGLE CELL ANALYSIS OF PATIENT METASTATIC RAPID AUTOPSY SAMPLES WITH FUNCTIONAL GENETICS AND 3D WHOLE ORGAN IMAGING OF LETHAL METASTASIS IN MOUSE. WE USE A HIGHLY EXIBLE GENETICALLY ENGINEERED MOUSE (GEM) MODEL OF LETHAL, ENDOGENOUS METASTATIC PROSTATE CANCER, TERMED RAPIDCAP. SPONTANEOUS PROGRESSION TO LETHAL METASTASIS IS SEEN IN ~70% OF PTEN/TRP53-MUTANT RAPIDCAP, SUGGESTING A CRITICAL STOCHASTIC PIONEER EVENT THAT SWITCHES A PTEN/ TRP53 NULL TUMOR CELL FROM INDOLENCE TO METASTATIC ESCAPE, SIMILAR TO A CRITICAL PIONEERING EVENT THAT CAUSES RELAPSE AFTER CASTRATION THERAPY. HOWEVER, CLASSICAL APPROACHES CAN ONLY CAPTURE AND REVEAL THE TIME AND PHYSICAL NATURE OF THESE PIONEERING EVENTS WHEN ALREADY THOUSANDS OR MILLIONS OF CELLS ARE INVOLVED. IN AIM 1, WE REVEAL, ISOLATE, AND ANALYZE SINGLE PIONEER CELLS IN SPACE AND TIME. WE COMBINE RAPIDCAP WITH SERIAL TWO PHOTON TOMOGRAPHY (STPT), WHICH ALLOWS US TO IMAGE WHOLE ORGANS AT SINGLE CELL RESOLUTION AND CONSTRUCT A 3D MAP OF THE TIME COURSE OF ESCAPE FROM INDOLENCE AND OF METASTATIC RELAPSE AFTER THERAPY. THIS GUIDES OUR ISOLATION OF CELL TYPES THAT THEN SERVE AS VALIDATED PROXIES FOR PIONEER CELLS OF ESCAPE OR RELAPSE. THROUGH AIM 2, WE SOLVE THE PTEN CO-MUTATION IMPASSE AND DENE GENES CO-DELETED WITH PTEN THROUGH SINGLE CELL WHOLE GENOME ANALYSIS OF HUMAN RAPID AUTOPSY SAMPLES. WE PRIORITIZE CANDIDATES BASED ON COMPREHENSIVE FUNCTIONAL MOLECULAR PROBING OF ALREADY ISOLATED PIONEER CELLS IN VITRO. THROUGH AIM 3, WE DEVELOP TWO NEW MODELING PLATFORMS FOR MORE EXIBLE VALIDATION OF CANDIDATE GENES AND PRINCIPLES BEHIND ESCAPE FROM INDOLENCE AND RELAPSE FROM CASTRATION THERAPY.

INTEGRATED RECOVERY SUPPORT SERVICES (RSS) MAT+ CARE MODEL - NEW HAMPSHIRE HAS BEEN AMONG THE TOP 10 STATES FOR DRUG MORTALITY DEATHS FOR FIVE YEARS, AND IS STILL IN THE PROCESS OF BUILDING AN EFFECTIVE INFRASTRUCTURE TO MANAGE THE PRESCRIPTION DRUG AND OPIOID EPIDEMIC. HARBOR HOMES, INC. D/B/A HARBOR CARE, AN INTEGRATED HEALTH AND HOUSING ORGANIZATION LOCATED IN NASHUA, NH, HAS PLAYED A LEADERSHIP ROLE IN THIS STATEWIDE RESPONSE AND SPECIALIZES IN TREATING ADULTS EXPERIENCING HOMELESSNESS AND AT-RISK PATIENTS WITH COMPLEX NEEDS. WITH SUPPORT FROM SAMHSA, HARBOR CARE WILL EXPAND AND ENHANCE SOUTHERN NH’S MAT TREATMENT AND RECOVERY CAPACITY BY BUILDING AND TESTING AN “INTEGRATED RECOVERY SUPPORT SERVICES (RSS) MAT+ CARE MODEL” TAILORED FOR ADULTS EXPERIENCING HOMELESSNESS. THIS INNOVATIVE MAT+ MODEL INTEGRATES COMMUNITY RECOVERY SUPPORT WORKERS (CRSWS) INTO THE CARE TEAM, INCORPORATING THE VITAL PEER RECOVERY SUPPORT FUNCTION WITHIN THE STANDARD NURSE CARE MANAGER-BASED OFFICE BASED OPIOID TREATMENT (OBOT) MODEL. HARBOR CARE WILL TREAT 600 HOMELESS/AT-RISK ADULTS WITH OUD OVER A 5-YEAR PERIOD AND REDUCE ADDICTION SEVERITY BY AN AVERAGE OF 50%, AND IMPROVE RECOVERY OUTCOMES FOR ADULTS WITH OUD BY 40% AT 6 MONTHS. AS PART OF THIS MODEL, WORKING WITH MAT PROVIDERS AND LICENSED BEHAVIORAL HEALTH CLINICIANS, NCMS AND CRSWS WILL ROLL OUT AND TEST A SET OF EVIDENCE-BASED PRACTICES (EBPS) OVER TIME AND ACCORDING TO THEIR SCOPE OF PRACTICE. THESE INCLUDE A COMPREHENSIVE TRAUMA-INFORMED APPROACH (WHICH COMBINES SEEKING SAFETY, EMDR, AND CBT), MOTIVATIONAL INTERVIEWING AND MOTIVATIONAL ENHANCEMENT THERAPY, THE MATRIX MODEL, CONTINGENCY MANAGEMENT, AND THE COMMUNITY REINFORCEMENT APPROACH, INTEGRATED DUAL DIAGNOSIS TREATMENT, AND SUPPORTED EMPLOYMENT. EVALUATION SUPPORT FROM MDRC WILL ENABLE HARBOR CARE TO BUILD AN EVIDENCE BASE FOR THE MAT+ EBPS AND DETERMINE WHICH COMBINATION OF EBPS BEST SUPPORT THE TARGET POPULATION IN TREATMENT AND LONG-TERM RECOVERY. IN YEARS 4 AND 5, HARBOR CARE WILL OFFER TRAINING AND TECHNICAL ASSISTANCE TO EXPAND THE INTEGRATED RSS MAT+ CARE MODEL TO AT LEAST THREE ADDITIONAL PROVIDER ORGANIZATIONS IN NH, REDUCING ILLICIT DRUG USE AND PRESCRIPTION DRUG MISUSE AND SUPPORTING ADULTS IN RECOVERY.

PROJECT TITLE WEARABLE MULTIPLEX BIOSENSORS TO MONITOR EXACERBATION RISK IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

EMPOWERING NEXTGEN ADVANCED BIOMEDICAL LEADERSHIP (ENABL)

DISRUPTED AUDITORY CORTICAL PLASTICITY AND BEHAVIOR IN A MODEL OF RETT SYNDROME

OP EARLY INTERVENTION SVCS W/RESPECT TO HIV DISEASE

THE HARBORVIEW MEDICAL CENTER MEDICATION ASSISTED TREATMENT-PRESCRIPTION DRUG AND OPIOID ADDICTION (SHORT TITLE: MAT PDOA) - PROJECT ABSTRACT SUMMARY PROJECT NAME: THE HARBORVIEW MEDICAL CENTER MEDICATION ASSISTED TREATMENT-PRESCRIPTION DRUG AND OPIOID ADDICTION PROJECT (HMC MAT-PDOA) PROJECT SUMMARY: THE HMC MAT-PDOA WILL EXPAND ACCESS TO INTEGRATED MEDICATION ASSISTED TREATMENT (MAT) FOR INDIVIDUALS WITH OPIOID USE DISORDER (OUD). BUILDING ON OUR SUCCESSFUL EXPERIENCE WITH A PROVEN MODEL OF PROVIDING MAT IN AN URBAN SAFETY NET MEDICAL SETTING, WE WILL EXPAND CAPACITY TO TREAT MORE PATIENTS AND ENHANCE SERVICES FOR PATIENTS WITH OUD PRESENTING FOR CARE IN THE HMC EMERGENCY DEPARTMENT (ED) AND HMC INPATIENT SERVICES. HMC-MAT-PDOA IS A COLLABORATIVE EFFORT BETWEEN HARBORVIEW MEDICAL CENTER AND WASHINGTON STATE TO ADDRESS THE RISING RATES OF OPIOID-RELATED PROBLEMS IN WASHINGTON STATE, INCLUDING OVERDOSE DEATHS AND ADDICTION TREATMENT ADMISSIONS. THE POPULATIONS TO BE SERVED ARE ADULTS WITH OUD IN KING COUNTY, WASHINGTON WHO ARE INITIATED ONTO MAT DURING AN INPATIENT HOSPITAL OR ED ADMISSION. STRATEGIES AND INTERVENTIONS INCLUDE THREE EVIDENCE-BASED PRACTICES (EBPS): 1) MAT WITH BUPRENORPHINE/NALOXONE, EXTENDED-RELEASE NALTREXONE, OR INJECTABLE BUPRENORPHINE, 2) THE MASSACHUSETTS NURSE CARE MANAGER MODEL FOR PROVIDING MAT IN MEDICAL SETTINGS, AND 3) PEER SUPPORT SERVICES. TO ADDRESS THE SPECIFIC NEEDS OF THE TARGET POPULATION, PEER NAVIGATION SERVICES AND INPATIENT ADDICTION MEDICINE PHYSICIAN CONSULTATIONS WILL BE USED TO ASSESS HOSPITALIZED PATIENTS FOR MAT, CHOOSE THE APPROPRIATE MEDICATION, INITIATE MAT, AND CONNECT PATIENTS WITH TRANSITIONAL AND PRIMARY CARE. PROJECT GOALS ARE TO: 1) INCREASE MAT CAPACITY USING A PROVEN MODEL FOR PROVIDING INTEGRATED SERVICES IN MEDICAL SETTINGS; 2) DEVELOP ENHANCED SERVICES FOR HOSPITALIZED AND ED PATIENTS WITH OUD AND HIGH RATES OF STIMULANT (PRIMARILY METHAMPHETAMINE) USE AND HOMELESSNESS; AND 3) ADVANCE DATA 2000 TRAINING FOR ELIGIBLE MEDICAL PROVIDERS SERVING MARGINALIZED PATIENTS IN MEDICAL SETTINGS. OBJECTIVES INCLUDE, BUT ARE NOT LIMITED TO: 1) SERVE 900 UNDUPLICATED PATIENTS OVER A FIVE-YEAR PERIOD (180 PATIENTS IN EACH YEAR), 2) ASSURE ACCESS TO COMPREHENSIVE SERVICES IN A CULTURALLY COMPETENT, PATIENT-CENTERED CARE MANNER, 3) REDUCE ADVERSE OUD-RELATED OUTCOMES AND SUBSTANCE USE FROM BASELINE TO 6-MONTH FOLLOW-UP, 4) MAXIMIZE RETENTION IN MAT, 5) REDUCE DISPARITIES IN MAT ACCESS, 6) INCREASE THE NUMBER OF HIGH-COST HOSPITALIZED PATIENTS WHO ARE ENGAGED IN MAT THROUGH INPATIENT PHYSICIAN CONSULTATIONS, 7) INCREASE THE USE OF PEER NAVIGATION SUPPORT FOR HIGH NEED PATIENTS, 8) REDUCE THE LIKELIHOOD OF MEDICATION DIVERSION, 8) INCREASE ACCESS TO HIV/HCV SCREENING AND TREATMENT, AND TOBACCO CESSATION SERVICES, 9) INCREASE REFERRALS FROM LOCAL JAILS/PRISONS, 10) SEEK SUSTAINABLE PROGRAM FINANCING, AND 11) TRAIN CLINICAL STAFF IN THE USE OF EBPS, INCLUDING DATA WAIVER TRAINING. THIS PROJECT WILL BE DONE IN COLLABORATION WITH THE WASHINGTON STATE RESEARCH AND DATA ANALYSIS, WHICH WILL PROVIDE TECHNICAL SUPPORT, ONGOING EVALUATION, AND POLICY SUPPORT.

DETECTION OF GENETIC AND EPIGENETIC CHANGES IN PRIMARY BREAST AND OVARIAN CANCER GENOMES UTILIZING GENOMIC MICROARRAYS

ORAL COMMENSAL FUNGI AND STRUCTURAL IMMUNITY - PROJECT SUMMARY WHILE THE FUNGUS CANDIDA ALBICANS HAS LARGELY BEEN STUDIED AS A PATHOGEN, ITS PRIMARY LIFESTYLE IS AS A COMMENSAL ON MUCOSAL SURFACES, INCLUDING THE ORAL CAVITY. MICROORGANISMS THAT OCCUPY MUCOSAL SURFACES ARE CRITICAL FOR APPROPRIATELY TUNING IMMUNE RESPONSES TO ENSURE EFFICIENT RESPONSES TO INVADING PATHOGENS WHILE LIMITING RESPONSES DIRECTED TOWARDS HOST TISSUES. IN THIS CONTEXT, COMMENSAL FUNGI PLAY IMPORTANT ROLES IN HOST IMMUNITY AND INFLAMMATION. FOR INSTANCE, C. ALBICANS COLONIZATION INDUCES CROSS-REACTIVE T CELLS AND INNATE MEMORY IN IMMUNE CELLS, A MECHANISM TERMED TRAINED IMMUNITY. ACCUMULATING EVIDENCE FROM OUR GROUP AND OTHERS HAVE CONVINCINGLY DEMONSTRATED THAT ORAL COMMENSAL COLONIZATION WITH C. ALBICANS INDUCES SPECIFIC IMMUNE RESPONSES, THEREFORE CONTRIBUTING TO MUCOSAL IMMUNE SYSTEM PLASTICITY. HOWEVER, THE FUNDAMENTAL IMMUNOLOGICAL CONSEQUENCES OF ORAL C. ALBICANS COLONIZATION ARE STILL NOT WELL UNDERSTOOD. HOST TISSUES MAINTAIN TRACES OR MEMORY AFTER MICROORGANISM ENCOUNTER THAT EXTEND BEYOND ADAPTIVE RESPONSES OF T AND B CELLS. THESE CHANGES INCLUDE PROFOUND STRUCTURAL REMODELING AND EPIGENETIC ALTERATIONS. ‘STRUCTURAL IMMUNITY’, THE IMMUNE RESPONSE WITHIN A TISSUE FRAMEWORK CREATED BY STRUCTURAL CELLS, SUCH AS ENDOTHELIAL AND EPITHELIAL CELLS, IS ESSENTIAL FOR MAINTAINING TOLERANCE AND THE DEVELOPMENT OF APPROPRIATE PROTECTIVE AND CONTROLLED IMMUNE RESPONSES. IN PROBING FOR STRUCTURAL PROCESSES THAT MAINTAIN EFFECTIVE MUCOSAL IMMUNITY IN THE ORAL CAVITY, WE IDENTIFIED TWO MECHANISMS WHICH ARE TUNED DURING ORAL COMMENSAL C. ALBICANS COLONIZATION, ORAL EPITHELIAL PROLIFERATION AND ANGIOGENESIS. OUR CENTRAL HYPOTHESIS IS THAT COMMENSAL C. ALBICANS EXPOSURE IN THE ORAL CAVITY ESTABLISHES MUCOSAL ‘STRUCTURAL IMMUNITY’ BY INDUCING ORAL EPITHELIAL TRAINED IMMUNITY, EPITHELIAL REMODELING, AND ANGIOGENESIS. THESE TISSUE REMODELING AND INNATE PRIMING EVENTS SERVE TO MAINTAIN EFFECTIVE MUCOSAL IMMUNITY, THUS PREVENTING ORAL FUNGAL OUTGROWTH OF THIS IMPORTANT COMMENSAL ORGANISM. THIS PROPOSAL WILL EVALUATE THE MOLECULAR MECHANISMS BY WHICH ORAL COMMENSAL C. ALBICANS INDUCE EPITHELIAL PROLIFERATION (AIM 1), AND ANGIOGENESIS (AIM1 AND 2). IN AIM1 WE WILL DELINEATE THE ROLE OF IL-22 IN MEDIATING ORAL STRUCTURAL IMMUNITY IN RESPONSE TO COMMENSAL C. ALBICANS COLONIZATION. IN AIM 2 WE WILL DETERMINE THE ROLE OF VEGF AS A MEDIATOR OF TRAINED AND STRUCTURAL IMMUNITY IN THE ORAL CAVITY.

MECHANISMS CONTROLLING EARLY HUMAN LUNG DEVELOPMENT

DYNAMIC REGULATION OF THE EPIGENOME DURING HEMATOPOIETIC DIFFERNTIATION

TRANSCRIPTIONAL REGULATION OF A. FUMIGATUS VIRULENCE

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - CONSTRUCTION - THE PROPOSED PROJECT AT SUMMIT PACIFIC MEDICAL CENTER AIMS TO EXPAND AND ENHANCE THE FACILITY TO MEET THE INCREASING HEALTHCARE DEMANDS OF OUR COMMUNITY. THE CURRENT 31,700 SQUARE FOOT FACILITY IS INADEQUATE TO ACCOMMODATE THE GROWING NEED FOR ACUTE AND EMERGENCY MEDICAL SERVICES. TO ADDRESS THESE NEEDS, THE PROJECT WILL INVOLVE SIGNIFICANT STRUCTURAL EXPANSIONS, RENOVATIONS, AND INFRASTRUCTURE IMPROVEMENTS, INCLUDING THE ADDITION OF A NEW ACUTE CARE UNIT, AN EXPANDED EMERGENCY DEPARTMENT, A NEW MRI SUITE, AND A RELOCATED HELIPAD TO IMPROVE PATIENT TRANSPORT EFFICIENCY. ADDITIONALLY, THE PROJECT WILL INCREASE PARKING CAPACITY AND CONSTRUCT A NEW FACILITY ENGINEERING BUILDING TO SUPPORT OPERATIONS. THESE ENHANCEMENTS WILL BENEFIT THE RESIDENTS OF ELMA AND NEIGHBORING TOWNS BY PROVIDING INCREASED HEALTHCARE SERVICES TO A DIVERSE POPULATION. THIS INCLUDES RESIDENTS, SURROUNDING COMMUNITIES, AND VULNERABLE GROUPS SUCH AS THE ELDERLY AND UNDERSERVED INDIVIDUALS. BY EXPANDING AND MODERNIZING THE MEDICAL CENTER, SUMMIT PACIFIC AIMS TO DELIVER ACCESSIBLE, HIGH-QUALITY MEDICAL CARE TO BETTER MEET THE NEEDS OF ITS GROWING PATIENT POPULATION. THE FUNDING WILL SPECIFICALLY BE UTILIZED FOR PHASE 2 OF THE CONSTRUCTION PROJECT INCLUDING CARPENTRY, FRAMING/DRYWALL, LANDSCAPING, FIRE SPRINKLER, ELECTRICAL, MECHANICAL, PLUMBING, MED-GAS, CIVIL, PAVING, EXTERIOR GLAZING, AND SIDING.

COLLABORATIVE RESEARCH: ARECIBO C3 - CENTER FOR CULTURALLY RELEVANT AND INCLUSIVE SCIENCE EDUCATION, COMPUTATIONAL SKILLS, AND COMMUNITY ENGAGEMENT -THIS AWARD ESTABLISHES A SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) EDUCATION AND RESEARCH CENTER AT THE FEDERALLY OWNED SITE IN ARECIBO, PUERTO RICO AND LOCATION OF THE ARECIBO OBSERVATORY. ARECIBO CENTER FOR CULTURALLY RELEVANT AND INCLUSIVE SCIENCE EDUCATION, COMPUTATIONAL SKILLS, AND COMMUNITY ENGAGEMENT (ARECIBO C3) WILL INTEGRATE SCIENCE (CIENCIA), COMPUTATION (COMPUTACI?N), AND COMMUNITY (COMUNIDAD)?GEOGRAPHICAL, DISCIPLINARY, AND CULTURAL?WITH THE OVERALL GOAL OF PROMOTING CULTURALLY-RELEVANT AND INCLUSIVE TEACHING WITH SCIENCE EDUCATION RESEARCH, OUTREACH, AND WORKFORCE DEVELOPMENT. ARECIBO C3 IS A COLLABORATION OF: COLD SPRING HARBOR LABORATORY, UNIVERSITY OF PUERTO RICO AT R?O PIEDRAS, UNIVERSITY OF MARYLAND BALTIMORE COUNTY, AND UNIVERSIDAD DEL SAGRADO CORAZ?N. ARECIBO C3 (A.K.A. THE CENTER) IS PURPOSE-BUILT TO ADVANCE STEM-EQUITY AND PROMOTE FULL PARTICIPATION IN THE BENEFITS OF STEM. THE SCHOLARLY COMMUNITY OF STEM EDUCATION RESEARCHERS WILL BENEFIT FROM THE OUTPUTS OF THE CENTER?S EDUCATION RESEARCH PROGRAMS. STEM STUDENTS, PROFESSIONAL EDUCATORS, AND THE PUBLIC WILL BENEFIT FROM THE CENTER?S SKILL BUILDING AND WORKFORCE DEVELOPMENT ACTIVITIES. ARECIBO C3 WILL SERVE AS A COLLABORATIVE HUB FOR STEM DISCOVERY AND EXPLORATION BY BUILDING UPON EXISTING PROGRAMS AND OPPORTUNITIES ESTABLISHED AT THE ARECIBO SITE BY PREVIOUS NSF PROGRAMS, WHILE ALSO CREATING NEW STEM EDUCATION, RESEARCH, AND OUTREACH PROGRAMS AND INITIATIVES. THE GOALS FOR THE CENTER ARE TO (1) PROMOTE STEM EDUCATION, LEARNING, AND TEACHING; (2) SUPPORT FUNDAMENTAL AND APPLIED STEM AND STEM EDUCATION RESEARCH; (3) BROADEN PARTICIPATION IN STEM; AND (4) BUILD AND STRENGTHEN COLLABORATIONS AND PARTNERSHIPS. THE PROPOSED SUITE OF EXPERIENCES AND RESEARCH WILL BE INNOVATIVE AND DIVERSE. RESEARCH ON STEM EDUCATION AND LEARNING WILL EXAMINE THE IMPACT OF MULTISENSORY TEACHING STRATEGIES IN SECONDARY AND POST-SECONDARY EDUCATION, AS WELL AS APPROACHES FOR ADULT LEARNING IN INFORMAL CONTEXTS, ULTIMATELY CONTRIBUTING TO INCREASING PARTICIPATION OF ALL PEOPLE ?WITH AND WITHOUT DISABILITIES? IN STEM. A COMPLEMENTARY PRIORITY WILL BE INVESTIGATING HOW CULTURALLY SUSTAINING PEDAGOGY SUPPORTS STUDENT STEM IDENTITY DEVELOPMENT. INTRODUCTORY RESEARCH EXPERIENCES FOR ALL WILL BE OFFERED THROUGH DNA BARCODE PUERTO RICO, AN EXPERIENCE USING DNA TO STUDY THE BIODIVERSITY OF THE ISLAND. MODELED ON COLD SPRING HARBOR LABORATORY DNA LEARNING CENTER BARCODING PROGRAMS, COLLABORATIONS WITH HIGH SCHOOLS AND SCIENCE CENTERS ACROSS PUERTO RICO WILL BE SERVED BY NEW ARECIBO C3 MOLECULAR AND COMPUTER LABORATORY SPACES AND EQUIPMENT LOANS. VISITOR GROUPS WILL ALSO ACCESS DNA LEARNING CENTER FIELD TRIPS AND SUMMER COURSES. VISITORS WILL ALSO EXPERIENCE A MULTISENSORY COURSE AND EXHIBITION FEATURING SENSORY EXPERIENCES OF DATA, SUCH AS THE MERGING OF BLACK HOLES OR BEHAVIOR OF BIOLUMINESCENT ORGANISMS. TEACHERS AND FACULTY WORKING WITH EXPERTS IN SCIENTIFIC AND EDUCATION RESEARCH WILL BE MENTORED TO CREATE, IMPLEMENT, AND ASSESS CURRICULA OF COURSE-BASED CONVERGENT RESEARCH EXPERIENCES FOR HIGH SCHOOL AND UNDERGRADUATES. ARECIBO C3 WILL CREATE WORKFORCE DEVELOPMENT OPPORTUNITIES FOCUSING ON DATA SCIENCE, COMPUTATION, AND BIOTECHNOLOGY. COMPUTATIONAL TRAINING WILL ALSO REACH INTO COMMUNITIES EMPOWERING WOMEN AND GIRLS IN PUBLIC HOUSING WITH DATA SCIENCE SKILLS AND CAREER OPPORTUNITIES. BIOTECHNOLOGY TRAINING AND CREDENTIALS WILL TIE TO LOCAL INDUSTRIES AND JOBS. ARECIBO C3 WILL FEATURE A MEETINGS PROGRAM THAT CONVENES RESEARCHERS, EDUCATORS, POLICY MAKERS, INDUSTRY PARTNERS, AND OTHER STAKEHOLDERS FOR THINK TANK STYLE CONFERENCES ON PRESSING STEM TOPICS. ADDITIONALLY, THE CENTER WILL PILOT A FELLOWSHIP PROGRAM IN WHICH PARTICIPANTS ARE TRAINED AND CERTIFIED IN SCIENTIFIC COMMUNITY MANAGEMENT. ARECIBO C3 FELLOWS WILL THEN SERVE AS AMBASSADORS USING RECENTLY ACQUIRED COLLABORATIVE STRATEGIES TO INVOLVE, ORGANIZE, TRAIN, SUPPORT THEIR PEERS IN COMMUNITY SCIENCE EXPERIENCES, AND BUILD COMMUNITIES OF PRACTICE. ULTIMATELY, ARECIBO C3 WILL FOSTER EQUITY-ENABLING STEM RESEARCH AND EDUCATION, ENRICH PUERTO RICO?S VIBRANT STEM COMMUNITIES, AND SERVE AS A CATALYST FOR INCLUSIVE STEM EDUCATION GLOBALLY. ARECIBO C3 IS JOINTLY FUNDED BY THE FOLLOWING PROGRAMS AT NSF: ADVANCING INFORMAL STEM LEARNING (AISL), THE ESTABLISHED PROGRAM TO STIMULATE COMPETITIVE RESEARCH (EPSCOR), DISCOVERY RESEARCH PREK-12 (DRK-12), INNOVATIVE TECHNOLOGY EXPERIENCES FOR STUDENTS AND TEACHERS (ITEST), HISPANIC-SERVING INSTITUTIONS (HSI), AND THE LOUIS STOKES ALLIANCES FOR MINORITY PARTICIPATION (LSAMP) PROGRAMS. 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.

SYNAPSE ENGULFMENT BY OLIGODENDROCYTE PRECURSOR CELLS: A NEW MECHANISM OF CIRCUIT REFINEMENT IN THE DEVELOPING BRAIN - PROJECT SUMMARY THE ESTABLISHMENT OF SYNAPTIC CONNECTIVITY DURING BRAIN DEVELOPMENT INVOLVES THE INITIAL FORMATION OF AN OVERABUNDANCE OF SYNAPSES FOLLOWED BY A REFINEMENT PROCESS IN WHICH SOME OF THESE SYNAPSES ARE MAINTAINED WHILE OTHERS ARE ELIMINATED. THE PRECISE ELIMINATION OF EXCESS SYNAPSES IS DRIVEN BY SENSORY EXPERIENCE DURING CRITICAL PERIODS OF EARLY POSTNATAL LIFE. IMPAIRMENTS IN SENSORY-DEPENDENT SYNAPSE ELIMINATION CONTRIBUTE TO NEURODEVELOPMENTAL DISORDERS SUCH AS AUTISM, UNDERSCORING THE IMPORTANCE OF THIS PROCESS FOR THE PROPER DEVELOPMENT AND FUNCTION OF NEURAL CIRCUITS. HOWEVER, ALTHOUGH NEURODEVELOPMENTAL DISORDERS ARE GROWING IN PREVALENCE AT AN ALARMING RATE, THERAPEUTIC STRATEGIES FOR TREATING THEM ARE SCARCE IN PART DUE TO A LACK OF INSIGHT INTO THE FACTORS THAT CONTROL SYNAPSE ELIMINATION IN THE HEALTHY BRAIN. A KEY GOAL OF THIS PROPOSAL IS TO UNCOVER NOVEL CELLULAR AND MOLECULAR MECHANISMS UNDERLYING THE ELIMINATION OF SYNAPSES DOWNSTREAM OF EXPERIENCE, THEREBY LAYING THE GROUNDWORK FOR NEW THERAPEUTIC APPROACHES TO TREAT DISORDERS OF POSTNATAL BRAIN DEVELOPMENT. WORK IN THE VISUAL SYSTEM OF THE MOUSE HAS REVEALED THAT NON-NEURONAL BRAIN CELLS, PREDOMINANTLY MICROGLIA AND ASTROCYTES, COORDINATE SYNAPSE ELIMINATION BEFORE THE ONSET OF VISUAL EXPERIENCE BY PHAGOCYTOSING EXCESS SYNAPSES. HOWEVER, DATA SUGGEST THAT THESE CELLS MAY NOT BE MAJOR REGULATORS OF SYNAPSE ELIMINATION DURING LATE PHASES OF DEVELOPMENT THAT ARE COORDINATED BY VISUAL EXPERIENCE. ON THE CONTRARY, WE RECENTLY DISCOVERED A KEY ROLE FOR A LESS WELL UNDERSTOOD CLASS OF GLIA, OLIGODENDROCYTE PRECURSOR CELLS (OPCS), IN ELIMINATING SYNAPSES IN RESPONSE TO EXPERIENCE THROUGH SYNAPTIC PHAGOCYTOSIS. THIS RESULT IS CONSISTENT WITH WIDE-SPREAD SPECULATION THAT OPCS, WHILE PREDOMINANTLY APPRECIATED FOR THEIR DIFFERENTIATION INTO MATURE OLIGODENDROCYTES, PLAY KEY ROLES IN THE BRAIN BEYOND MYELINATION. IN LINE WITH THIS POSSIBILITY, OUR DATA SUGGEST THAT OPCS ARE ESSENTIAL FOR SHAPING FUNCTIONAL NEURAL CIRCUITS DURING THE MATURATION OF THE BRAIN. IN THIS APPLICATION, WE PROPOSE A MULTI-DISCIPLINARY STRATEGY TO TEST THE HYPOTHESIS THAT THE ENGULFMENT OF SYNAPSES BY OPCS IS A CORE MECHANISM UNDERLYING THE SENSORY-DEPENDENT ELIMINATION OF FUNCTIONAL SYNAPSES IN THE DEVELOPING BRAIN. IN AIM 1, WE WILL EMPLOY VIRAL AND TRANSGENIC TOOLS TO CHARACTERIZE THE SPATIO-TEMPORAL DYNAMICS AND ACTIVITY-DEPENDENT BASIS OF SYNAPTIC ENGULFMENT BY OPCS USING IN VIVO TWO-PHOTON MICROSCOPY. IN AIM 2, WE WILL APPLY PHYSIOLOGICAL AND BEHAVIORAL ASSAYS TO DETERMINE THE CONSEQUENCES OF SYNAPTIC ENGULFMENT BY OPCS ON BRAIN FUNCTION IN THE INTACT ANIMAL. IN AIM 3, WE WILL MERGE UNBIASED TRANSCRIPTOMIC AND CRISPR- BASED SCREENING TECHNIQUES WITH A CANDIDATE-BASED APPROACH FOCUSED ON THE PHAGOCYTIC RECEPTOR LRP1 TO REVEAL MOLECULAR PATHWAYS UNDERLYING THE ENGULFMENT OF SYNAPSES BY OPCS. ALTOGETHER, WE EXPECT THESE STUDIES TO ESTABLISH SYNAPSE ENGULFMENT BY OPCS AS A NEW MECHANISM LINKING EXPERIENCE TO NEURAL CIRCUIT DEVELOPMENT, AND TO LAY THE FOUNDATION FOR FUTURE STUDIES GEARED TOWARD MODIFYING OPC FUNCTION AS A POTENTIAL THERAPEUTIC STRATEGY FOR TREATING NEURODEVELOPMENTAL DISORDERS.

MECHANISMS AND CIRCUMVENTION OF DAPTOMYCIN RESISTANCE IN STREPTOCOCCUS MITIS

CELL ADHESION MOLECULES IN AUTISM: A WHOLE-BRAIN STUDY OF GENETIC MOUSE MODELS

RHO REGULATOR-MEDIATED SIGNALING IN INTERNEURON DEVELOPMENT

COMMUNITY PROJECT GRANTS CONGRESSIONALLY DELEGATED

IMPROVE EXISTING AIRPORT

BIOPHYSICAL MODELING OF CIS-REGULATORY COMPLEXES IN TRANSCRIPTION AND SPLICING USING MASSIVELY PARALLEL REPORTER ASSAYS

QUANTITATIVE ANALYSIS OF THE BIOLOGICAL FORCES AND THEIR CONTEXT IN TISSUE PATTERNING

EMOTIONAL MODULATION OF NEURAL AND BEHAVIORAL RESPONSES TO SOCIAL CUES BY LOCUS COERULEUS

NOVEL ALGORITHM DEVELOPMENT, USER SUPPORT AND MAINTENANCE FOR STAR