Mac Incorporated

AMERICA MAKES PARTNERSHIP (AMP) THE NATIONAL ADDITIVE MANUFACTURING INNOVATION INSTITUTE

THIS IS AN FFY2021 SECTION 5307 ARP FUNDING APPLICATION (WASHINGTON DC AREA UZA) IN THE AMOUNT OF $136695827 REPRESENTING 100% FEDERAL SHARE OF THE TOTAL ELIGIBLE AMOUNT. THIS GRANT UTILIZES ARP FUNDING TO PREVENT PREPARE FOR AND RESPOND TO CORONAVIRUS. THE APPLICATION SCOPE OF WORK INCLUDES OPERATING ASSISTANCE FOR THE POTOMAC AND RAPPAHANNOCK TRANSPORTATION COMMISSION (PRTC) VIRGINIA RAILWAY EXPRESS (VRE) AND FREDERICKSBURG REGIONAL (FRED) TRANSIT . VRE AND FRED TRANSIT ARE SUB-RECIPIENTS TO PRTC. THE SPLIT LETTER DATED JUNE 1 2021 IS ATTACHED IN TRAMS. PURPOSE: THE PURPOSE OF THIS AWARD IS TO PROVIDE OPERATING ASSISTANCE TO PRTC AND PRTCS SUBRECIPIENTS VRE AND FRED TRANSIT TO ASSIST IN RECOVERING FROM COVID-19. ACTIVITIES TO BE PERFORMED: FUNDS WILL BE USED TO COVER EXPENSES FOR BUS AND COMMUTER RAIL SERVICE PARTICULARLY SUCH EXPENSES THAT WOULD HAVE NORMALLY BEEN PAID BY PASSENGER REVENUE INCLUDING OPERATOR AND STAFF SALARIES AND FRINGES FUEL AND OTHER ONGOING OPERATING AND MAINTENANCE EXPENSES.EXPECTED OUTCOMES: FUNDING WILL PERMIT PRTC VRE AND FRED TRANSIT TO CONTINUE TO PROVIDE OPERATIONS THAT WOULD OTHERWISE HAVE TO BE CUT DUE TO LACK OF FUNDING.INTENDED BENEFICIARIES: PRTC VRE FRED TRANSIT AND THE RIDERS THAT RELY ON ITS SERVICE WILL BENEFIT FROM CONTINUED SERVICES PERMITTING WORKERS TO GET TO WORK AND RIDERS TO GET TO ESSENTIAL SERVICES.SUBRECIPIENT ACTIVITIES: VRE AND FRED TRANSIT PRTCS SUBRECIPIENT WILL RECEIVE ARP FUNDS FOR OPERATING ASSISTANCE.THE RECIPIENT AGREES THAT IF IT RECEIVES FEDERAL FUNDING FROM THE FEDERAL EMERGENCY MANAGEMENT AGENCY (FEMA) OR THROUGH A PASS-THROUGH ENTITY THROUGH THE ROBERT T. STAFFORD DISASTER RELIEF AND EMERGENCY ASSISTANCE ACT A DIFFERENT FEDERAL AGENCY OR INSURANCE PROCEEDS FOR ANY PORTION OF A PROJECT ACTIVITY APPROVED FOR FTA FUNDING UNDER THIS GRANT AGREEMENT IT WILL PROVIDE WRITTEN NOTIFICATION TO FTA AND REIMBURSE FTA FOR ANY FEDERAL SHARE THAT DUPLICATES FUNDING PROVIDED BY FEMA ANOTHER FEDERAL AGENCY OR AN INSURANCE COMPANY.PER ARP ACT REQUIREMENTS THE PROJECTS IN THIS APPLICATION ARE NOT REQUIRED TO BE PROGRAMMED IN THE LONG-RANGE TRANSPORTATION PLAN STATEWIDE TRANSPORTATION PLAN OR STATEWIDE TRANSPORTATION IMPROVEMENT PROGRAM.PRTC CERTIFIES THAT THE EXPENDITURE FOR SECURITY PROJECTS IS NOT NECESSARY PURSUANT TO 49 U.S.C. 5307(C)(1)(J)).

PROMOTING THE QUALITY OF MEDICINES PLUS (PQM+) PROGRAM

PROMOTING QUALITY OF MEDICINES PROGRAM TO ASSIST IN EFFICACY AND SAFETY OF MEDICINES IN USAID AREAS OF INTEREST

TAS::89 0328::TAS RECOVERY ACT - SMART GRID INVESTMENT GRANT PROGRAM

PRTC VRE FRED SECTION 5307 CARES ACT OPERATING AND CAPITAL PROJECTS

TAS::89 0328::TAS RECOVERY - INSTALL 280,000 SMART METERS EQUIPPED WITH THE NETWORK INTERFACE; INSTITUTE DYNAMIC PRICING PROGRAMS, AND DEPLOY DISTRIB

THIS IS AN FFY 2021 SECTION 5307 CRRSAA APPLICATION IN THE AMOUNT OF $80723700 REPRESENTING 100% FEDERAL SHARE OF THE TOTAL ELIGIBLE AMOUNT. THIS APPLICATION UTILIZES CRRSAA FUNDING TO PREVENT PREPARE FOR AND RESPOND TO CORONAVIRUS. THE APPLICATION SCOPE OF WORK INCLUDES OPERATING ASSISTANCE FOR THE POTOMAC AND RAPPAHANNOCK TRANSPORTATION COMMISSION (PRTC) VIRGINIA RAILWAY EXPRESS (VRE) AND FREDERICKSBURG REGIONAL TRANSIT (FRED). VRE AND FRED TRANSIT ARE SUB-RECIPIENTS TO PRTC. THIS APPLICATION INCLUDES OVERLAPPING PERIODS OF PERFORMANCE FOR ARP GRANT AWARD VA-2022-030-00 FOR EXPENSES THAT WOULD HAVE NORMALLY BEEN PAID BY PASSENGER REVENUE INCLUDING OPERATOR AND STAFF SALARIES AND FRINGES FUEL AND OTHER ONGOING OPERATING AND MAINTENANCE EXPENSES.THE SPLIT LETTER DATED MARCH 20 2021 IS ATTACHED IN TRAMS.THE RECIPIENT AGREES THAT IF IT RECEIVES FEDERAL FUNDING FROM THE FEDERAL EMERGENCY MANAGEMENT AGENCY (FEMA) OR THROUGH A PASS-THROUGH ENTITY THROUGH THE ROBERT T. STAFFORD DISASTER RELIEF AND EMERGENCY ASSISTANCE ACT A DIFFERENT FEDERAL AGENCY OR INSURANCE PROCEEDS FOR ANY PORTION OF A PROJECT ACTIVITY APPROVED FOR FTA FUNDING UNDER THIS GRANT AGREEMENT IT WILL PROVIDE WRITTEN NOTIFICATION TO FTA AND REIMBURSE FTA FOR ANY FEDERAL SHARE THAT DUPLICATES FUNDING PROVIDED BY FEMA ANOTHER FEDERAL AGENCY OR AN INSURANCE COMPANY. THE RECIPIENT CERTIFIES THAT IT AND ITS SUBRECIPIENTS AND CONTRACTORS THAT ARE PROVIDERS OF PUBLIC TRANSPORTATION HAVE NOT FURLOUGHED ANY EMPLOYEES SINCE MARCH 27 2020 (THE ENACTMENT DATE OF THE CARES ACT).PER CRRSSA ACT REQUIREMENTS THE PROJECTS IN THIS APPLICATION ARE NOT REQUIRED TO BE PROGRAMMED IN THE LONG-RANGE TRANSPORTATION PLAN STATEWIDE TRANSPORTATION PLAN OR STATEWIDE TRANSPORTATION IMPROVEMENT PROGRAM.PURPOSE: THE PURPOSE OF THIS AWARD IS TO PROVIDE OPERATING ASSISTANCE TO PRTC VRE AND FRED TRANSIT TO ASSIST IN RECOVERING FROM COVID-19. ACTIVITIES TO BE PERFORMED: FUNDS WILL BE USED TO COVER EXPENSES FOR BUS AND COMMUTER RAIL SERVICE PARTICULARLY SUCH EXPENSES THAT WOULD HAVE NORMALLY BEEN PAID BY PASSENGER REVENUE INCLUDING OPERATOR AND STAFF SALARIES AND FRINGES FUEL AND OTHER ONGOING OPERATING AND MAINTENANCE EXPENSES.EXPECTED OUTCOMES: FUNDING WILL PERMIT PRTC VRE AND FRED TRANSIT TO CONTINUE TO PROVIDE OPERATIONS THAT WOULD OTHERWISE HAVE TO BE CUT DUE TO LACK OF FUNDING.INTENDED BENEFICIARIES: PRTC VRE FRED TRANSIT AND THE RIDERS THAT RELY ON ITS SERVICE WILL BENEFIT FROMCONTINUED SERVICES PERMITTING WORKERS TO GET TO WORK AND RIDERS TO GET TO ESSENTIAL SERVICES.SUBRECIPIENT ACTIVITIES: VRE AND FRED TRANSIT PRTCS SUBRECIPIENTS WILL RECEIVE CRRSAA FUNDS FOR OPERATING ASSISTANCE.

THE PURPOSE OF THIS COOPERATIVE AGREEMENT IS TO FUND RESEARCH TO THE RECIPIENT IN THE AMOUNT OF 1,927,669 ON CONTRACT HR0011-16-2-0029.

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STATEMENT OF WORK ENTITLED 'NATIONAL ADDITIVE MANUFACTURING INNOVATION INSTITUTE (NAMII)' DATED 20 JUL 12

FFY17-FFY18 SECTIONS 5337 AND 5307 RAIL PROJECTS

PA-22 FYPD & PA-20 T&TA/CDA

THE NATIONAL ADDITIVE MANUFACTURING INNOVATION INSTITUTE

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GRANT WITH INOVIO PHARMACEUTICALS, INC. FOR PROPOSAL ENTITLED, "IMMEDIATE AND PERSISTENT PROTECTION AGAINST EBOLA ZAIRE"

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BUS AND RAIL STATE OF GOOD REPAIR PROJECTS FY13-FY15

CARES ACT - INSTITUTIONAL PORTION OF HIGHER EDUCATION EMERGENCY RELIEF FUND

APPLICATION PURPOSE: THIS AWARD WILL FUND STATION IMPROVEMENTS AT VRES ALEXANDRIA AND FRANCONIA-SPRINGFIELD STATIONS AND THE EXPANSION OF THE VRE CROSSROADS MAINTENANCE AND STORAGE FACILITY TO ACCOMMODATE RAILCARS LOCOMOTIVES AND SPARE EQUIPMENT.; ACTIVITIES PERFORMED: ACTIVITIES INCLUDE REPLACING AN AT-GRADE PEDESTRIAN TRACK CROSSING WITH ELEVATORS TO CONNECT THE TWO PLATFORMS; DESIGN AND CONSTRUCTION OF AN EXTENSION TO THE EXISTING WEST VRE PLATFORM AT FRANCONIA-SPRINGFIELD AND VRE CROSSROADS YARD EXPANSION.; EXPECTED OUTCOMES: PROJECTS WILL SIGNIFICANTLY IMPROVE PASSENGER SAFETY AND ACCESSIBILITY AND OPERATIONAL EFFICIENCY.; INTENDED BENEFICIARIES: VRE AND VRE RAIL PASSENGERS.; SUBRECIPIENT ACTIVITIES: ACTIVITIES IN THIS AWARD ARE FOR VRE AS A SUB-RECIPIENT TO PRTC.

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TANZANIA PEOPLES DEFENSE FORCES HIV/AIDS WORKPLACE PROGRAM

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SUPERCONDUCTING LOGICALLY-ENCODED EXTENSIBLE QUBIT (SLEEQ)

THE POTOMAC AND RAPPAHANNOCK TRANSPORTATION COMMISSION (PRTC) IS APPLYING A TOTAL OF $8852610 IN SECTION 5337 STATE OF GOOD REPAIR AND $1557690 OF SECTION 5307 URBANIZED AREA FUNDS TOWARDS VARIOUS RAIL PROJECTS INCLUDING DEBT-SERVICE ON RAILCARS AND FACILITY STATE OF GOOD REPAIR.FUNDS BEING USED IN THIS APPLICATION ARE AS FOLLOW:5337 FFY18: RAIL $69039795337 FFY19: RAIL $19486315307 FFY17: RAIL $1557690THE NON-FEDERAL SHARE WILL BE PROVIDED BY THE COMMONWEALTH OF VIRGINIA AND THE LOCAL JURISDICTIONS. THE REMAINING FFY19 5337 FUNDS OF $20622679 WILL BE APPLIED FOR AT A LATER DATE AS WELL AS THE REMAINING FFY17 5307 FUNDS OF $5703337. PRTC IS A DIRECT RECIPIENT. THIS APPLICATION FOR SECTION 5337 AND 5307 FUNDS IS CONSISTENT WITH THE DESIGNATED RECIPIENT SPLIT LETTERS OF 7/17/17 5/22/2018 AND 4/23/2019 ATTACHED TO THIS APPLICATION. BY EXECUTING THIS GRANT WE CERTIFY THAT PROJECTS FUNDED WITH SECTION 5337 IN THIS GRANT ARE ALIGNED WITH THE SEPTEMBER 2018 TAM PLAN AND ARE IDENTIFIED IN ITS INVESTMENT PRIORITIZATION SECTION.PURPOSE OF AWARD THIS AWARD WILL PROVIDE FOR THE ONGOING DEBT SERVICE FOR RAILCARS AND HELP MAINTAIN FACILITY ASSETS.ACTIVITIES TO BE PERFORMED ACTIVITIES INCLUDE MAINTENANCE AND/OR UPGRADE PROJECTS THROUGHOUT THE VRE SYSTEM TO MAINTAIN THE STATIONS PLATFORMS PARKING GARAGES AND LOTS IN A STATE OF GOOD REPAIR AND TO PERFORM ONGOING DEBT SERVICE FOR RAILCARS.EXPECTED OUTCOMES MAINTAINING FACILITY ASSETS WILL PROVIDE FOR A SAFE AND RELIABLE COMMUTER EXPERIENCE. REPLACING THE OLDEST RAILCARS WILL PROVIDE A MORE RELIABLE AND SAFE COMMUTING TRIP FOR THE VRE RIDERSSUBRECIPIENT ACTIVITIES: ACTIVITIES IN THIS AWARD ARE FOR VRE AS A SUB-RECIPIENT TO PRTC.

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APPLICATION PURPOSE: THIS AWARD WILL FUND THE PURCHASE OF 3 VRE PROPERTY INTERESTS.; ACTIVITIES PERFORMED: ACTIVITIES INCLUDE THE PURCHASE OF 3 PROPERTY INTERESTS: TITLE TO THE SEMINARY YARD IN ALEXANDRIA VA; TITLE TO THE BROAD RUN CORRIDOR IN MANASSAS VA; AND A PERMANENT EASEMENT FOR THE EXISTING VRE MANASSAS LINE STATION PLATFORMS.; EXPECTED OUTCOMES: ACQUISITION OF THE PROPERTY INTERESTS WILL HELP ADVANCE THE GOAL OF ADDITIONAL COMMUTER RAIL SERVICE AND PROVIDE A FOUNDATION FOR IMPROVEMENTS IN CAPACITY RELIABILITY AND FLEXIBILITY TO SUPPORT FUTURE GROWTH.; INTENDED BENEFICIARIES: VRE AND VRE RAIL SERVICE PASSENGERS; SUBRECIPIENT ACTIVITIES: ALL ACTIVITIES IN THIS AWARD WILL BE CONDUCTED BY VRE.

APPLICATION PURPOSE: THIS AWARD WILL HELP TO FUND VRE TRACKS STATIONS AND STORAGE YARD ACCESS FEES AND ALEXANDRIA STATION IMPROVEMENTS.; ACTIVITIES PERFORMED: ACTIVITIES INCLUDE MAINTENANCE RE TRACKS STATIONS AND STORAGE YARD ACCESS FEES AND ALEXANDRIA STATION IMPROVEMENT VRE TRACKS STATIONS AND STORAGE YARD ACCESS FEES AND ALEXANDRIA STATION IMPROVEMENTS; EXPECTED OUTCOMES: MAINTAINING FACILITY ASSETS WILL PROVIDE FOR A SAFE AND RELIABLE COMMUTER EXPERIENCE.; INTENDED BENEFICIARIES: VRE RAIL SERVICE PASSENGERS.; SUBRECIPIENT ACTIVITIES: ACTIVITIES IN THIS AWARD ARE FOR VRE AS A SUB-RECIPIENT TO PRTC.

APPLICATION PURPOSE: THIS AWARD WILL HELP TO MAINTAIN FACILITY ASSETS AND TO PURCHASE TWENTY-ONE (21) EXPANSION RAILCARS.; ACTIVITIES PERFORMED: ACTIVITIES INCLUDE MAINTENANCE AND/OR UPGRADE PROJECTS THROUGHOUT THE VRE SYSTEM TO MAINTAIN THE STATIONS PLATFORMS PARKING GARAGES AND LOTS IN A STATE OF GOOD REPAIR AND TO PURCHASE EXPANSION RAILCARS.; EXPECTED OUTCOMES: MAINTAINING FACILITY ASSETS WILL PROVIDE FOR A SAFE AND RELIABLE COMMUTER EXPERIENCE. PURCHASING NEW RAILCARS WILL PROVIDE A MORE RELIABLE AND SAFE COMMUTING TRIP FOR THE VRE RIDERS; INTENDED BENEFICIARIES: VRE RAIL SERVICE PASSENGERS.; SUBRECIPIENT ACTIVITIES: ACTIVITIES IN THIS AWARD ARE FOR VRE AS A SUB-RECIPIENT TO PRTC.

SEVERELY DISTRESSED PUBLIC HSN

GROSSMONT COLLEGE CARES ACT INSTITUTIONAL SUPPORT

APPLICATION PURPOSE: THE PURPOSE OF THIS GRANT IS TO FUND DEBT-SERVICE ON RAILCARS POSITIVE TRAIN CONTROL CONSTRUCTION OF CROSSROADS YARD HEAVY MAINTENANCE FACILITY AND HIM BUS PREVENTIVE MAINTENANCE.; ACTIVITIES PERFORMED: ACTIVITIES INCLUDE IMPLEMENTATION OF POSITIVE TRAIN CONTROL CONSTRUCTION OF CROSSROADS MAINTENANCE FACILITY AND BUS MAINTENANCE.; EXPECTED OUTCOMES: MAINTAINING FACILITY ASSETS WILL PROVIDE FOR A SAFE AND RELIABLE COMMUTER EXPERIENCE.; INTENDED BENEFICIARIES: VRE RAIL SERVICE PASSENGERS AND PRTC BUS PASSENGERS.; SUBRECIPIENT ACTIVITIES: ACTIVITIES IN THIS AWARD ARE FOR VRE AS A SUB-RECIPIENT TO PRTC.

APPLICATION PURPOSE: THIS AWARD WILL FUND STATION IMPROVEMENTS AT VRES LENFANT AND CRYSTAL CITY STATIONS.; ACTIVITIES PERFORMED: ACTIVITIES INCLUDE PLANNING DESIGN PERMITTING AND CONSTRUCTION FOR AN EXPANDED VRE LENFANT STATION ALONG WITH AN ADDITIONAL MAINLINE TRACK AND AN EXPANDED AND RELOCATED STATION AND PLATFORM FOR THE VRE CRYSTAL CITY STATION.; EXPECTED OUTCOMES: THE EXPANDED STATIONS WILL SUPPORT SIMULTANEOUS BOARDING OF TWO FULL-LENGTH TRAINS AND WILL IMPROVE STATION ACCESS AND CUSTOMER CONVENIENCE WHILE ALSO IMPROVING SERVICE RELIABILITY.; INTENDED BENEFICIARIES: VRE AND VRE RAIL SERVICE PASSENGERS; SUBRECIPIENT ACTIVITIES: ALL ACTIVITIES IN THIS AWARD WILL BE CONDUCTED BY VRE.

HIGHER EDUCATION EMERGENCY FINANCIAL AID GRANTS TO STUDENTS UNDER THE CARES ACT

PHASE II CLINICAL TRAILS OF NNZ-2566

APPLICATION PURPOSE: THIS PURPOSE OF THIS GRANT IS FOR PREVENTIVE MAINTENANCE TO OFF-SET THE KEOLIS TRANSIT SERVICES CONTRACT FOR MAINTAINING BUSES OWNED BY PRTC AND IN PRTCS FACILITY. ADDITIONALLY THE PURPOSE OF THE BUS REPLACEMENT IS TO REPLACE 40-FT BUSES THAT HAVE MET THEIR USEFUL LIFE. FINALLY THE PURPOSE OF THE BUS SHELTER PROGRAM IS TO REPLACE EXISTING BUS SHELTERS THAT HAVE MET THEIR USEFUL LIFE.; ACTIVITIES PERFORMED: FUNDS FOR PREVENTIVE MAINTENANCE WILL BE USED TO MAINTAIN BUSES AND OTHER FLEET VEHICLES AS WELL AS THE MAINTENANCE BAYS AND THE BUS STORAGE YARD WHICH INCLUDES A BUS WASH AND FUELING BAYS. THE PURPOSE FOR THE BUS ACQUISITION/REPLACEMENT IS TO PURCHASE FOUR (4) 40 FOOT BUSES TO REPLACE BUSES THAT HAVE MET THEIR USEFUL LIFE.; EXPECTED OUTCOMES: MAINTAINING THE FLEET REPLACING EXISTING SHELTERS AND PURCHASING REPLACEMENT BUSES WILL PROVIDE FOR A MORE RELIABLE BUS SERVICE.; INTENDED BENEFICIARIES: CITIZENS OF PRINCE WILLIAM COUNTY AND THE CITIES OF MANASSAS AND MANASSAS PARK.; SUBRECIPIENT ACTIVITIES: N/A

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THE LHSPLA ACTIVITY IS ENVISIONED AS A FIVE-YEAR ACTIVITY. THIS ACTIVITY WILL CONTRIBUTE TO THE POOL OF COMMODITIES NEEDED FOR PATIENTS UNDERGOING HIV ANTIRETROVIRAL THERAPY (ART). THE ITEMS TO BE PROCURED UNDER THE LHSPLA ACTIVITY WILL COMPLEMENT THOSE PROCURED THROUGH TWO USAID/WASHINGTON GLOBAL HEALTH BUREAU SUPPLY CHAIN PROCUREMENT MECHANISMS, THE GLOBAL HEALTH COMMODITY SUPPLY CHAIN-PROCUREMENT AND SUPPLY MANAGEMENT (GHSC-PSM) PROJECT AND THE GLOBAL HEALTH COMMODITY SUPPLY CHAIN-RAPID TEST KITS (GHSC-RTK) PROJECT. ANNEX ONE FOR COMPLETE LIST OF USAID SUPPLY CHAIN IMPLEMENTING PARTNERS)

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SURFACE-CODE MULTI-QUBIT FUNCTIONALITY WITH SUPERCONDUCTING QUBITS

FLOOD MITIGATION ASSISTANCE

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GROSSMONT COLLEGE CARES ACT SUPPORT TO STUDENTS

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FY13 & 14 CAPITAL PROJECTS

FY11/12 RAIL TRACK LEASES FLEX FUND

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FY11 & FY 12 CAPITAL PROJECTS RAIL/

INFLATION REDUCTION ACT (IRA): END-TO-END, MULTI-MODAL, HIGH RESOLUTION METHANE INVENTORY QUANTIFICATION (E2E-METHANE-IQ) THE OBJECTIVE OF THIS SCOPE IS TO DEVELOP AN END-TO-END, MULTI-MODAL, HIGH RESOLUTION METHANE INVENTORY QUANTIFICATION (E2E-METHANE-IQ) TECHNOLOGY, WHICH WILL BE (I) FULLY VALIDATED THROUGH MULTIPLE MEASUREMENT CAMPAIGNS IN ALL MAJOR BASINS IN THE WESTERN UNITED STATES (INCLUDING UINTA, FOUR CORNERS, SAN JOAQUIN, GREEN RIVER, MONTANA, BIG HORN, ETC.), (II) AGNOSTIC TO THE INDIVIDUAL SENSING TECHNOLOGIES, (III) FULLY SCALABLE AND OPERATIONALLY FROM EQUIPMENT TO REGIONAL LEVEL AND FROM MINUTES TO MONTHS, AND (IV) READILY EXTENSIBLE TO ACCOMMODATE SPECIFIC NEEDS IN CERTAIN REGIONS OR APPLICATIONS.

FY09-11 RAIL & BUS PROJ (FLEX FUNDS

RAIL FLEXED FUNDS PROJECT FY18

CRITICAL PATH MANUFACTURING SECTOR RESEARCH INITIATIVE (U01)

PA-22 FYPD

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MVRTA CARES ACT OPERATING EXPENSES

TITLE III LIGHT WEIGHT AMMUNITION AND ARMOR PROGRAM

HEALTH CENTER CLUSTER

FY11/12 FIXED GUIDEWAY PROJECT-VRE/

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APPLICATION PURPOSE: THIS AWARD WILL HELP TO FUND VARIOUS RAIL PROJECTS INCLUDING DEBT-SERVICE ON RAIL CARS YARD AND STATION SECURITY CAMERAS AND ROLLING STOCK ASSET MANAGEMENT.; ACTIVITIES PERFORMED: ACTIVITIES INCLUDE PURCHASE AND INSTALLATION OF YARD AND STATION SECURITY CAMERAS AND MAINTAINING OF RAIL CARS.; EXPECTED OUTCOMES: MAINTAINING SECURITY OF VRE FACILITIES AND STATIONS AND WILL PROVIDE FOR A SAFE AND RELIABLE COMMUTER EXPERIENCE.; INTENDED BENEFICIARIES: VRE RAIL SERVICE PASSENGERS.; SUBRECIPIENT ACTIVITIES: ACTIVITIES IN THIS AWARD ARE FOR VRE AS A SUB-RECIPIENT TO PRTC.

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PRODUCTION OF TARGETED NULL MUTATIONS FOR 10,000 GENES IN C57BL/6 ES CELLS

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FFY14 - FFY16 SECTION 5307 BUS AND RAIL PROJECTS

APPLICATION PURPOSE: THIS AWARD WILL FUND VARIOUS VRE STATION MAINTENANCE AND/OR UPGRADE PROJECTS THROUGHOUT THE SYSTEM TO MAINTAIN THE STATIONS PLATFORMS PARKING GARAGES LOTS AND INFORMATION TECHNOLOGY SYSTEMS IN A STATE OF GOOD REPAIR.; ACTIVITIES PERFORMED: ACTIVITIES INCLUDE UNINTERRUPTIBLE POWER SUPPLY (UPS) REPLACEMENTS AT VRE HEADQUARTERS AND ALL VRE STATIONS; VARIABLE MESSAGE SIGN (VMS) REPLACEMENT; NEW COMMUNICATIONS CABINETS AT STATIONS; UPGRADES TO STATION INFORMATION DISPLAYS; NETWORK SECURITY AND RELIABILITY UPGRADES; ACCESS CONTROL SYSTEM UPGRADES; AND CONTINUED MAINTENANCE AND/OR UPGRADES THROUGHOUT THE VRE SYSTEM TO MAINTAIN THE STATIONS PLATFORMS PARKING GARAGES AND LOTS IN A STATE OF GOOD REPAIR.; EXPECTED OUTCOMES: MAINTAINING FACILITY ASSETS AND INFORMATION TECHNOLOGY SYSTEMS WILL PROVIDE FOR A SAFE AND RELIABLE COMMUTER EXPERIENCE FOR VRE PASSENGERS WHILE IMPROVING OPERATIONAL EFFICIENCY. ; INTENDED BENEFICIARIES: VRE RAIL SERVICE PASSENGERS; SUBRECIPIENT ACTIVITIES: ALL ACTIVITIES IN THIS AWARD WILL BE CONDUCTED BY VRE.

HEALTH CENTER CLUSTER

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FY12 RAIL/BUS PROJECTS (FLEX FUNDS)

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CUYAMACA COLLEGE CARES ACT INSTITUTIONAL SUPPORT

PA-22, PA-20

PAD FOR LOCAL PARTNERS PROGRAM

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF LHP588 IN SUBJECTS WITH P. GINGIVALIS-POSITIVE ALZHEIMER'S DISEASE - SUMMARY/ABSTRACT A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF LHP588 IN SUBJECTS WITH P. GINGIVALIS-POSITIVE ALZHEIMER'S DISEASE GIVEN THE INCREASING INCIDENCE OF AD WORLDWIDE, THERE IS AN URGENT UNMET NEED FOR PRECISION MEDICINE APPROACHES THAT COULD PREVENT OR DELAY COGNITIVE DECLINE EXPERIENCED BY ALZHEIMER’S DISEASE (AD) PATIENTS. MOUNTING EVIDENCE SUGGESTS THAT LIFE EXPOSURE TO BRAIN-PENETRANT PATHOGENS COULD CONTRIBUTE TO THE ETIOLOGY OF AD. ONE MICROBIAL AGENT RECENTLY ASSOCIATED WITH AD IS PORPHYROMONAS GINGIVALIS (PG). PG IS BEST KNOWN FOR ITS ROLE IN CHRONIC PERIODONTITIS , BUT EPIDEMIOLOGIC AND OTHER STUDIES ALSO STRONGLY IMPLY ITS CONTRIBUTION TO COGNITIVE DECLINE. CRITICALLY, PG VIRULENCE FACTORS, PROTEASES CALLED GINGIPAINS HAVE BEEN IDENTIFIED IN POST-MORTEM AD BRAINS, AT RATES SIGNIFICANTLY HIGHER THAN AGE-MATCHED CONTROLS. GINGIPAIN LOADS HAVE SHOWN A POSITIVE CORRELATION WITH AD SEVERITY, BRAIN TAU LEVELS, AND UBIQUITIN PATHOLOGY. OUR TEAM PREVIOUSLY DEVELOPED A SMALL-MOLECULE, BRAIN-PENETRANT, ORALLY BIOAVAILABLE, FIRST-GENERATION, COVALENT GINGIPAIN INHIBITOR CALLED COR388 (ATUZAGINSTAT), WHICH MITIGATED MANY AD- ASSOCIATED NEUROPATHOLOGICAL FEATURES IN PRECLINICAL IN VITRO AND ANIMAL STUDIES. AFTER OBTAINING U.S. FOOD & DRUG ADMINISTRATION (FDA) PERMISSION, WE CONDUCTED A LARGE, PHASE-II/III, PLACEBO-CONTROLLED, RANDOMIZED CLINICAL TRIAL OF ATUZAGINSTAT ADMINISTERED TO MILD-TO-MODERATE DEMENTIA SUBJECTS (MMSE RANGING 12-24) FOR 48 WEEKS. TARGET ENGAGEMENT WAS VERIFIED ALONG WITH DOSE-DEPENDENT REDUCTION OF SYSTEMIC PG INFECTION. THE PRESPECIFIED SUBGROUP ANALYSIS MOST RELEVANT TO THE MECHANISM OF ACTION INDICATED DOSE-DEPENDENT EFFICACY IN PATIENTS WITH PG-POSITIVE (PG+) SALIVA (N=242), WITH A REDUCTION OF THE AD ASSESSMENT SCALE-COGNITIVE SUBSCALE 11 (ADAS-COG11) SCORES BY 57% COMPARED TO BASELINE (P=0.02). HOWEVER, BECAUSE OF HEPATIC SAFETY CONCERNS, DEVELOPMENT OF ATUZAGINSTAT WAS DISCONTINUED. WE, AT LIGHTHOUSE PHARMACEUTICALS, HAVE NOW DEVELOPED A SECOND-GENERATION, ORALLY BIOAVAILABLE GINGIPAIN INHIBITOR CALLED LHP588. RIGOROUS IN VITRO AND ANIMAL STUDIES HAVE DEMONSTRATED IMPROVED TARGET ENGAGEMENT AND REDUCED TOXICITY OF LHP588 COMPARED TO ATUZAGINSTAT. IN A PHASE I STUDY COMBINING A SINGLE-ASCENDING-DOSE AND A 10-DAY MULTIPLE-ASCENDING-DOSE, LHP588 WAS WELL TOLERATED AND THERE WAS NO EVIDENCE OF HEPATIC TOXICITIES AT ANY DOSE. USING OUR EXPERIENCE WITH ATUZAGINSTAT AND THE DEVELOPMENT OF LHP588, WE FORMULATED THE HYPOTHESIS THAT LHP588 CAN PROVIDE INCREASED TARGET ENGAGEMENT WITH REDUCED SAFETY RISKS TO SLOW DOWN COGNITIVE DECLINE IN PATIENTS SUFFERING FROM PG-POSITIVE (PG+) MILD-TO-MODERATE AD. TO TEST OUR HYPOTHESIS, WE WILL DEPLOY A RIGOROUSLY DESIGNED PHASE II, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED, 3-ARM, PARALLEL GROUP CLINICAL TRIAL TERMED SPRING (STOPPING PROGRESSION OF PORPHYROMONAS GINGIVALIS-ASSOCIATED AD). THOROUGH SCREENING WILL SELECT AD SUBJECTS WITH PG+ SALIVA AND PLASMA P-TAU-217 LEVELS ABOVE 0.42 PG/ML, WHICH IS ASSOCIATED WITH AMYLOID PLAQUE POSITIVITY ACROSS RACIAL AND ETHNIC GROUPS. ENROLLED STUDY PARTICIPANTS (N=300; MINIMUM OF 30% OF DIVERSE SUBJECTS) WILL BE RANDOMIZED 1:1:1 TO 25 OR 50 MG LHP588 TAKEN ORALLY ONCE-A-DAY, OR MATCHING PLACEBO, FOR 48 WEEKS. IMPORTANTLY, THE FDA PROVIDED A “STUDY MAY PROCEED” LETTER AFTER REVIEW OF OUR INVESTIGATIONAL NEW DRUG (IND) APPLICATION. IN AIM 1, WE WILL ASSESS SAFETY AND TOLERABILITY IN AD SUBJECTS ADMINISTERED LHP588. IN AIM 2, WE WILL TEST FOR TARGET ENGAGEMENT BY MEASURING PG DNA LEVELS IN SALIVA AND ANTI-PG IGG LEVELS IN SERUM. IN AIM 3, WE WILL DETERMINE DRUG EFFICACY VS. PLACEBO USING CLINICAL ASSESSMENTS OF DEMENTIA, I.E., COGNITION (ADAS- COG11, WHICH IS THE PRIMARY EFFICACY MEASURE), OTHER CLINICAL MEASURES, BIOMARKERS, INCLUDING BRAIN ATROPHY ESTIMATED BY VMRI, AND PLASMA LEVELS OF P-TAU-217. SUCCESS OF OUR SPRING TRIAL WILL WARRANT CARRYING OUT AT LEAST ONE LARGER CONFIRMATORY PHASE III STUDY FOR FUTURE

PURPOSE: EXTEND RUNWAY. ACTIVITIES TO BE PERFORMED/EXPECTED OUTCOMES: THIS PROJECT EXTENDS RUNWAY 5/23 TO 7,100 FEET TO MEET FEDERAL AVIATION ADMINISTRATION STANDARDS. THIS GRANT FUNDS THE FOURTH PHASE, WHICH CONSISTS OF SITE PREPARATION. INTENDED BENEFICIARY: THIS GRANT WILL PROVIDE FEDERAL FUNDING FOR AIRPORTS ASSOCIATED WITH MACON, GEORGIA.

FY13/14 RAIL & BUS PROJ (FLEX FUNDS)

GLOBAL AUTONOMOUS LANGUAGE EXPLOITATION (GALA)

APPLICATION PURPOSE: THIS IS A MERRIMACK VALLEY TRANSIT (MEVA) REQUEST FOR $11439427 IN 5307 FUNDS APPORTIONED TO THE BOSTON-MA-NH-RI UZA. $5079697 IN FY24 FUNDS ($1434897 IN 5307 URBAN FORMULA FUNDS AND $3644800 IN CMAQ 5307 FLEX FUNDS). PLUS $6359730 IN 5307 URBAN FORMULA CARRYOVER FUNDS ($5925251 IN FY23 FUNDS AND $434479 IN FY21 FUNDS). THESE FUNDS ARE FOR A PROGRAM OF CAPITAL PROJECTS NEEDED TO KEEP MEVA VEHICLES EQUIPMENT AND FACILITIES IN A STATE OF GOOD REPAIR AND OPTIMALLY SERVE THE CULTURALLY AND LINGUISTICALLY RICH MERRIMACK VALLEY COMMUNITIES WE OPERATE IN. THIS GRANT INCLUDES $2856398 OF MATCHING FUNDS FROM MASSDOT. THE FOLLOWING PROJECTS WILL BE FUNDED UNDER THIS APPLICATION:; ACTIVITIES PERFORMED: (1) ACQUISITION OF FOUR (4) REPLACEMENT 29-FT BUSES: $1916832 IN CMAQ FUNDS TRANSFERRED TO FTA ($2396040 TOTAL) (2) ACQUISITION OF TEN (10) REPLACEMENT 35-FT BUSES: $6531996 IN FTA FUNDS ($8164995 TOTAL). $1727968 OF THESE FUNDS ARE CMAQ FUNDS FLEXED TO FTA TO COVER THE INCREMENTAL COSTS OF HYBRID ENGINES FOR SIX (6) OF THESE BUSES.(3) ACQUISITION OF EIGHT (8) SUVS TO BE USED IN PARATRANSIT REVENUE SERVICE: $332000 IN FTA FUNDS ($415000 TOTAL). BUDGET INCLUDES ELECTRONICS NEEDED FOR SERVICE LIKE SECURITY CAMERAS RADIOS AND MANIFEST TABLETS.(4) ACQUISITION OF ONE (1) REPLACEMENT SUPERVISORY VEHICLE: $42928 IN FTA FUNDS ($53660 TOTAL). (5) IMPROVEMENTS TO MCGOVERN INTERMODAL TRANSPORTATION CENTER IN LAWRENCE MA TO FACILITATE UTILIZING THE INTERMODAL CENTER AS THE CENTRAL BUS HUB FOR LAWRENCE: $1500000 IN FTA FUNDS ($1875000 TOTAL).(6) MISCELLANEOUS SUPPORT EQUIPMENT AND FACILITY REPAIR: $509192 IN FTA FUNDS ($636490 TOTAL) (7) UPGRADE TO THE ACCESS CONTROL SYSTEM INCLUDING THE ADDITION OF NEW DOORS FOR ALL MEVA FACILITIES. $172000 IN FTA FUNDS ($215000 TOTAL).(7) PHASE 1 FEASIBILITY STUDY AND PRELIMINARY DESIGN FOR THE EXPANSION OF MEVAS MAINTENANCE FACILITY: $434479 IN FTA FUNDS ($543099 TOTAL). NOTE: THIS PROJECT UTILIZED PRE-BIL AUTHORIZATION FUNDING SO IS UNDER A SEPARATE PROJECT AND SCOPE.; EXPECTED OUTCOMES: THIS PROGRAM OF CAPITAL AND PLANNING PROJECTS WILL ENABLE MEVA TO CONTINUE PROVIDING A RELIABLE RESPONSIVE AND SAFE SERVICE TO THE PUBLIC THAT WILL HELP KEEP EXISTING RIDERS AND ATTRACT NEW RIDERS BY KEEPING OUR VEHICLES EQUIPMENT AND FACILITIES IN A STATE OF GOOD REPAIR AND OPTIMIZING SERVICE IN ORDER TO FULLY RESPECT OUR RIDERS TIME AND PROVIDE THE COMMUNITIES WE SERVE WITH THE LEVEL OF TRANSIT SERVICE THEY NEED AND DESERVE.; INTENDED BENEFICIARIES: CONSISTENT WITH MEVAS MISSION TO PUT OUR CUSTOMERS FIRST THE PRIMARY BENEFICIARIES WILL BE TRANSIT RIDERS ACROSS THE MERRIMACK VALLEY. OUR SERVICE AREA DEPENDS ON QUALITY TRANSIT FOR CRITICALLY NEEDED ESSENTIAL TRAVEL TO WORK MEDICAL APPOINTMENTS EDUCATION TRAINING AND EVERYDAY LIFE. THE LARGEST CITY IN OUR SERVICE DISTRICT LAWRENCE IS 83% LATINO ACCORDING TO THE MOST RECENT CENSUS DATA AND HAS THE LOWEST PER CAPITA INCOME OF ANY MUNICIPALITY IN THE COMMONWEALTH OF MASSACHUSETTS. MEVAS SERVICE AREA WHICH ENCOMPASSES THE THREE GATEWAY CITIES OF LAWRENCE METHUEN AND HAVERHILL AS WELL AS AMESBURY AND NEWBURYPORT AND THE TOWNS OF ANDOVER NORTH ANDOVER BOXFORD GEORGETOWN GROVELAND MERRIMAC WEST NEWBURY SALISBURY NEWBURY ROWLEY AND NORTH READING HAS A POPULATION OF OVER 300000.; SUBRECIPIENT ACTIVITIES: NONE

HEALTH CENTER CLUSTER

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PURPOSE: THIS IS A MERRIMACK VALLEY REGIONAL TRANSIT AUTHORITY (MVRTA) REQUEST FOR $10946038 IN CARRYOVER 5307 URBAN FORMULA FUNDS ($2304896 IN FY19 FUNDS $5293024 IN FY20 FUNDS AND $3348118 IN FY21 FUNDS) APPORTIONED TO THE BOSTON-MA-NH-RI UZA. THIS GRANT INCLUDES $3571722 OF MATCHING FUNDS FROM THE STATE AND $20000 FROM THE MERRIMACK VALLEY PLANNING COMMISSION.ACTIVITIES TO BE PERFORMED:OPERATING ASSISTANCE: $644945 IN FTA FUNDS ($1289890 TOTAL) PREVENTIVE MAINTENANCE: $2889070 IN FTA FUNDS ($3611338 TOTAL) ADA OPERATING ASSISTANCE: $1441305 IN FTA FUNDS ($1808632 TOTAL) SHORT RANGE TRANSIT PLANNING: $80000 IN FTA FUNDS ($100000 TOTAL) REPLACEMENT OF NINE (9) 35-FT BUSES: $3269223 IN FTA FUNDS ($4458030 TOTAL)SUPERVISORY VEHICLE REPLACEMENT: $39095 IN FTA FUNDS ($48970 TOTAL) REPAIR/EQUIPMENT FOR ADMINISTRATIVE AND MAINTENANCE FACILITY: $545600 IN FTA FUNDS ($682000 TOTAL) RIVERBANK STABILIZATION CONSTRUCTION: $2036800 IN FTA FUNDS ($2546000 TOTAL) EXPECTED OUTCOMES: THIS PROGRAM OF OPERATING CAPITAL AND PLANNING PROJECTS WILL ENABLE THE MVRTA TO CONTINUE PROVIDING A RELIABLE RESPONSIVE AND SAFE SERVICE TO THE PUBLIC THAT WILL HELP KEEP EXISTING RIDERS AND ATTRACT NEW RIDERS.INTENDED BENEFICIARIES: RIDERS IN MVRTAS SERVICE AREA WHICH ENCOMPASSES THE CITIES OF LAWRENCE METHUEN HAVERHILL AMESBURY AND NEWBURYPORT AND THE TOWNS OF ANDOVER NORTH ANDOVER BOXFORD GEORGETOWN GROVELAND MERRIMAC WEST NEWBURY SALISBURY NEWBURY ROWLEY AND NORTH READING WITH AN APPROXIMATE POPULATION OF 300000. SUBRECIPIENT ACTIVITIES: NONE.MVRTA ALONG WITH ALL OTHER DESIGNATED RECIPIENTS IN THE BOSTON-MA-NH-RI UZA EXECUTED A SPLIT LETTER FOR FY19 FY20 FY21 5307 URBAN FORMULA FUNDS ON 6/6/19 3/5/20 2/22/21 RESPECTIVELY (ATTACHED). ALL ACTIVITIES IN THIS APPLICATION ARE PROGRAMMED IN THE FY22 ELEMENT OF THE MA STIP WHICH WAS APPROVED BY FTA ON 8/2/21. PLANNING ACTIVITIES ARE PROGRAMMED IN THE FY2022 UPWP APPROVED BY THE MVMPO ON 6/28/21. MVRTA SIGNED THE FY22 CERTIFICATIONS ASSURANCES IN TRAMS ON 2/4/22. MVRTA DUNS #090159711 HAS BEEN ENTERED INTO TRAMS. MVRTA IS CURRENT WITH ALL CIVIL RIGHTS SUBMISSIONS.

FY09-12 RAIL & BUS PROJ (FLEX FUNDS

ALLIANCE FOR DIGITAL AND FINANCIAL SERVICES

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IBM TJ WATSON RESEARCH CENTER: BASE AWARD 1566-1504: ENLITENED PROJECT TITLE: MULTIWAVELENGTH OPTICAL TRANSCEIVERS INTEGRATED ON NODE (MOTION)

PHASE III STUDY OF A NICOTINE VACCINE FOR SMOKING CESSATION

MONOCLONAL IMMUNOPROTECTANTS FOR SELECT AGENTS TOXINS (MAB-SAT)

THE POTOMAC AND RAPPAHANNOCK TRANSPORTATION COMMISSION (PRTC) IS APPLYING FFY2018 SECTION 5339 BUS AND BUS FACILITIES FUNDS APPORTIONED TO THE WASHINGTON DC-MARYLAND-VIRGINIA URBANIZED AREA IN THE AMOUNT OF $1679901 FOR ACQUISITION OF REPLACEMENT BUSES.PRTC IS ALSO APPLYING FFY19 OF SECTION 5337 STATE OF GOOD REPAIR HIM BUS FUNDS APPORTIONED TO THE WASHINGTON DC-MARYLAND-VIRGINIA URBANIZED AREA IN THE AMOUNTS OF $600093 FOR PREVENTIVE MAINTENANCE FOR MOTOR BUS VEHICLES AND RELATED FACILITIES.FURTHER PRTC IS APPLYING FFY2017 SECTION 5307 FUNDS APPORTIONED TO THE WASHINGTON DC-MARYLAND-VIRGINIA URBANIZED AREA IN THE AMOUNT OF $5160283 (THE REMAINDER OF THE FFY17 5307 FUNDS OF $543054 WILL BE APPLIED FOR AT A LATER DATE) FOR PREVENTIVE MAINTENANCE AND THE PURCHASE AND INSTALLATION OF SECURITY EQUIPMENT. NON-FEDERAL SHARE OF THE SECTION 5307 SECURITY PROJECT IS BEING PROVIDED BY SOFT MATCH FROM THE VANPOOL PROGRAM CAPITAL COST OF THE VEHICLE ACQUISITIONS AS OUTLINED IN THE SOFT MATCH FROM VANPOOL WORKSHEET ATTACHED TO THIS GRANT UNDER APPLICATION DOCUMENTS.THE NON-FEDERAL SHARE OF THE SECTION 5307 5337 AND 5339 FUNDS WILL BE PROVIDED BY THE COMMONWEALTH OF VIRGINIA AND THE LOCAL JURISDICTIONS. PRTC IS A DIRECT RECIPIENT. THIS APPLICATION FOR SECTION 5339 5337 AND 5307 FEDERAL ASSISTANCE IS CONSISTENT WITH THE DESIGNATED RECIPIENT SPLIT LETTERS OF 7/17/17 AND 5/22/2018 AND 4/23/2019 ATTACHED TO THIS APPLICATION.

NEIGHBORHOOD STABILIZATION PRG

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TRADE ADJUSTMENT ASSISTANCE COMMUNITY COLLEGE AND CAREER TRAINING

HEALTH CENTER CLUSTER

THE PLAY TO LEARN ACTIVITY GOAL IS TO INCREASE THE NUMBER OF CHILDREN IN DJIBOUTI BENEFITING FROM HIGH-QUALITY, EQUITABLE, SAFE, AND INCLUSIVE ECE SERVICES. THE ACTIVITY’S OBJECTIVE IS TO IMPROVE ACCESS, QUALITY, CAPACITY & EFFECTIVENESS OF SAFE AND INCLUSIVE ECE SERVICES.

FY13/14 RAIL TRACK LEASES FLEX FUND

BUS AND RAIL FLEXED FUNDS PROJECTS FY17

CUYAMACA COLLEGE CARES ACT SUPPORT TO STUDENTS

FY10 CAPITAL PROJECTS RAIL

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THIS COOPERATIVE AGREEMENT SHALL BE PERFORMED IAW THE STATEMENT OF WORK (SOW) ENTITLED , "REAL-TIME ASSESSMENT & AUGMENTATION OF COGNITIVE CAPABILITIES IN EXTREME ENVIRONMENTS"

NALMEFENE IMPLANT FOR THE LONG-TERM TREATMENT OF OPIOID USE DISORDER

CAPITAL FUND RECOVERY ACT (COMPETITIVE)

THE PURPOSE OF THIS MODIFICATION IS TO PROVIED INCREMENTAL FUNDING IN THE AMOUNT OF $150,000.00 UNDER A MAARD FROM THE PHILIPPINES.

FY14/15 RAIL TRACK LEASES FLEX FUND

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CHITIMACHA 190 CTGP CR 1

PUBLIC HOUSING CAPITAL FUND

SQUADBOT V2: HIGH PERFORMANCE HUMANOID FOR URBAN EXPLORATION

CLINICAL DEVELOPMENT OF A NOROVIRUS GASTROENTERITIS VACCINE

SCALING THE NATIONAL DIABETES PREVENTION PROGRAM IN UNDERSERVED AREAS - 2017

APPLICATION PURPOSE: THE PURPOSE OF THIS GRANT IS TO FUND FOR ACQUISITION OF REPLACEMENT BUSES PREVENTIVE MAINTENANCE FOR MOTOR BUS VEHICLES AND FOR INSTALLATION OF SURVEILLANCE AND SECURITY EQUIPMENT. ; ACTIVITIES PERFORMED: ACTIVITIES INCLUDE PURCHASE OF REPLACEMENT BUSES MAINTENANCE FOR MOTOR BUS VEHICLES AND INSTALLATION OF SURVEILLANCE AND SECURITY EQUIPMENT.; EXPECTED OUTCOMES: MAINTAINING SECURITY OF PRTC FACILITIES AND STATIONS AND WILL PROVIDE FOR A SAFE AND RELIABLE COMMUTER EXPERIENCE.; INTENDED BENEFICIARIES: PRTC AND PRTC BUS PASSENGERS.; SUBRECIPIENT ACTIVITIES: NO SUBRECIPIENT ACTIVITIES.

FY14/15 RAIL TRACK LEASES FLEX FUND

APPLICATION PURPOSE: THE PURPOSE OF THIS GRANT IS FOR PREVENTIVE MAINTENANCE TO OFF-SET THE KEOLIS TRANSIT SERVICES CONTRACT FOR MAINTAINING BUSES OWNED BY PRTC AND IN PRTCS FACILITY. ADDITIONALLY THE PURPOSE OF THE BUS REPLACEMENT IS TO REPLACE THREE (3) 40-FT BUSES THAT HAVE MET THEIR USEFUL LIFE.; ACTIVITIES PERFORMED: FUNDS FOR PREVENTIVE MAINTENANCE WILL BE USED TO MAINTAIN BUSES AND OTHER FLEET VEHICLES AS WELL AS THE MAINTENANCE BAYS AND THE BUS STORAGE YARD WHICH INCLUDES A BUS WASH AND FUELING BAYS. THE PURPOSE FOR THE BUS ACQUISITION/REPLACEMENT IS TO PURCHASE THREE (3) 40 FOOT BUSES TO REPLACE BUSES THAT HAVE MET THEIR USEFUL LIFE.; EXPECTED OUTCOMES: MAINTAINING THE FLEET REPLACING EXISTING SHELTERS AND PURCHASING REPLACEMENT BUSES WILL PROVIDE FOR A MORE RELIABLE BUS SERVICE.; INTENDED BENEFICIARIES: CITIZENS OF PRINCE WILLIAM COUNTY AND THE CITIES OF MANASSAS AND MANASSAS PARK.; SUBRECIPIENT ACTIVITIES: N/A

A PHASE 2 CLINICAL TRIAL OF SRX246 IN FRAGILE X SYNDROME (FXS)

INSTITUTIONAL PORTION OF CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND

THROUGHPUT OPTIMIZED POEM SYSTEM (TOPS)

HIV/AIDS CARE AND PREVENTION

A SIX-MONTH, RCT OF PROBUPHINE SAFETY AND EFFICACY IN OPIOID ADDICTION

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NEW CLASS OF PBP INHIBITORS TO ADDRESS PBP2-MEDIATED RESISTANCE IN NEISSERIA GONORRHOEAE

QUANTUM VALIDATION AND VERIFICATION METHODS FOR SUPERCONDUCTING QUBITS

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COMMUNICATION WITH A LEARNING COLLABORATIVE PROBLEM SOLVING AGENT

EFFICACY, SAFETY, AND PHARMACOKINETIC STUDY OF BICX104 NALTREXONE SUBCUTANEOUS IMPLANT ALONE AND IN COMBINATION WITH BUPROPION FOR THE TREATMENT OF METHAMPHETAMINE USE DISORDER (MUD). - WE ARE PROPOSING BICX104, A SUBCUTANEOUS, LONG-DURATION NALTREXONE IMPLANTABLE PELLET, ALONE OR IN CONJUNCTION WITH BUPROPION FOR THE TREATMENT OF METHAMPHETAMINE USE DISORDER (MUD). CLINICAL STUDIES HAVE SUPPORTED THE POTENTIAL USE OF NALTREXONE ALONE IN THE TREATMENT OF MUD, AS WELL AS NALTREXONE IN COMBINATION WITH BUPROPION TO SIGNIFICANTLY ATTENUATE METHAMPHETAMINE (METH) USE. METH USE IS CURRENTLY OCCURRING IN LARGE NUMBERS WITH AN ESTIMATED 2 MILLION PEOPLE PER YEAR IN THE U.S. AND A 43% INCREASE IN USAGE FROM 2015-2019. EFFICACY STUDIES SHOW THAT COMPLIANCE TO NTX THERAPY IS SUPERIOR TO PLACEBO FOR MAINTAINING ABSTINENCE TO SUBSTANCE ABUSE, WITH SOME EVIDENCE THAT MONTHLY INJECTIONS ARE SUPERIOR TO ORAL DOSES. HOWEVER, NONCOMPLIANCE SEVERELY LIMITS NTX'S CLINICAL EFFICACY. THE INSERTION OF A SUSTAINED-RELEASE NTX DEPOT PELLET FORMULATION SUCH AS BICX104 CAN BOTH ENSURE COMPLIANCE AND PROVIDE THERAPEUTIC BLOOD LEVELS OVER LONG TIME PERIODS. THERE ARE NO APPROVED MEDICATIONS FOR MUD, LEAVING PATIENTS, CARE GIVERS, AND SOCIETY AT RISK TO THE EPIDEMIC OF METH ABUSE AND ASSOCIATED MORBIDITY AND DEATH. THE PROPOSAL INVESTIGATES BICX104 ALONE AND BICX104/BUP IN COMPARISON WITH A DOUBLE PLACEBO GROUP (IMPLANT AND TABLET) TO DEMONSTRATE SAFETY, PHARMACOKINETICS (PK), AND EFFICACY IN MUD. THERE IS AN FDA-APPROVED IND IN PLACE AND A COMPLETED PHASE 1 STUDY OF BICX104 AS OF MARCH 22, 2023 TO ENABLE THE TRIALS DESCRIBED IN THIS PROPOSAL. DR. MALLON HAS ASSEMBLED AN OUTSTANDING CLINICAL RESEARCH TEAM PAIRED WITH OUTSTANDING FACILITIES THAT HAS A TRACK RECORD OF SUCCESS IN THIS PROGRAM. AIM 1: DETERMINE THE CLINICAL SAFETY PROFILE OF BICX104 IN METHAMPHETAMINE USE DISORDER PATIENTS IN PHASE 1B EXPLORATORY STUDIES. EVALUATE THE SAFETY OF BICX104 IN THE PATIENT POPULATION AND THE ACHIEVEMENT OF CLINICALLY RELEVANT NTX PLASMA CONCENTRATIONS. DELIVERABLES: ACHIEVE MINIMUM EFFECTIVE CONCENTRATION (MEC) OF >1 NG/ML NTX PLASMA CONCENTRATIONS FOR AT LEAST 10 WEEKS IN ALL TREATMENT GROUPS. DEMONSTRATE THAT AT LEAST ONE OF THE TREATMENT ARMS IS SUFFICIENTLY WELL TOLERATED TO ENABLE PHASE 2 CLINICAL TRIAL. AIM 2: ESTABLISH COMPARATIVE EFFICACY OF BICX104 AND BUPROPION, ALONE AND IN COMBINATION IN DECREASING CLINICAL MARKERS OF METHAMPHETAMINE ABUSE IN METHAMPHETAMINE USE DISORDER PATIENTS. THIS PHASE 2 TRIAL TESTS EFFICACY IN A SUFFICIENTLY POWERED POPULATION OF MUD PATIENTS. SUCCESS IN THIS PHASE 2 WILL INFORM THE DESIGN OF A DEFINITIVE PHASE 3 TRIAL OF EFFICACY THAT WILL ENABLE DRUG APPROVAL. DELIVERABLE: SAFETY AND TOLERABILITY OF AT LEAST ONE TREATMENT ARM. CLINICALLY MEANINGFUL EFFICACY OF AT LEAST ONE TREATMENT COMPARED TO PLACEBO. MILESTONE: PROGRESSION TO PHASE 3 EFFICACY TRIAL TO ENABLE FDA APPROVAL.

DEVELOPMENT OF AN INTRANASAL, LONG DURATION OPIOID ANTAGONIST TO TREAT OPIOID OVERDOSE

ESTABLISHING A GRAM-NEGATIVE PERMEATION RULE SET LEVERAGING A UNIQUE SMALL MOLECULE LIBRARY

ARRA-AMESBURY ITC & HAVERHILL ADM.

WHITEWATER CREEK WATERSHED PROJECT WITH MACON COUNTY BOARD OFCOMMISSIONERS, GEORGIA- INFRASTRUCTURE INVESTMENT AND JOBS ACT (IIJA)

BEAVER CREEK WATERSHED PROJECT WITH MACON COUNTY BOARD OF COMMISSIONERS,GEORGIA-INFRASTRUCTURE INVESTMENT AND JOBS ACT (IIJA)

FY07 FIXED GUIDEWAY PROJECTS-VRE/PRTC

NON-ELECTRIC DISPOSABLE IV INFUSION PUMP

NANO-COMPOSITE MULTILAYER COATINGS FOR AIRCRAFT

NALMEFENE IMPLANT FOR THE LONG-TERM TREATMENT OF OPIOID USE DISORDER - PROJECT SUMMARY: NALMEFENE IMPLANT FOR THE LONG-TERM TREATMENT OF OPIOID USE DISORDER THE U.S. CURRENTLY FACES A MAJOR CRISIS FROM THE INCREASING NUMBER OF DEATHS DUE TO OPIOID OVERDOSE AMONG AMERICANS AFFLICTED WITH THE CHRONIC MEDICAL CONDITION CALLED OPIOID USE DISORDER (OUD). HARM FROM OPIOID MISUSE AND ADDICTION ALSO COMES AT A HUGE ECONOMIC COST. PHARMACOTHERAPY FOR OUD WITH AN OPIOID AGONIST, OR FOLLOWING DETOXIFICATION WITH AN OPIOID ANTAGONIST, IS SAFE AND EFFECTIVE, AND CAN REDUCE OR ELIMINATE WITHDRAWAL SYMPTOMS, BLUNT OR BLOCK THE EFFECTS OF ILLICIT OPIOIDS, AND REDUCE OR ELIMINATE CRAVINGS. HOWEVER, AN OUD SUBJECT IN REMISSION HAS A HIGH CHANCE OF RELAPSE TO OPIOID USE; WHICH CAN OCCUR AT ANY TIME - FROM A FEW DAYS TO MONTHS FOLLOWING DETOXIFICATION. PROPHYLACTIC TREATMENT WITH OPIOID ANTAGONISTS CAN BLOCK THE EFFECT OF OPIOID USE AND CAN BE AN EFFECTIVE TREATMENT FOR PREVENTING OUD RELAPSE FOLLOWING DETOXIFICATION AND POTENTIAL OVERDOSE DEATH; HOWEVER, LOW PATIENT COMPLIANCE TO FREQUENT DOSING NECESSARY TO MAINTAIN BRAIN OPIOID RECEPTOR BLOCKADE HAS PREVENTED WIDESPREAD ADOPTION. THERE IS AN URGENT UNMET NEED FOR A CHRONIC TREATMENT PARADIGM CAPABLE OF PROVIDING ENHANCED COMPLIANCE FOR 6-MONTHS OR LONGER TO PREVENT OUD RELAPSE AND RENARCOTIZATION IN DETOXIFIED SUBJECTS. TITAN'S PROPRIETARY SUBDERMAL IMPLANTS CAN PROVIDE LONG-TERM, NON- FLUCTUATING THERAPEUTIC LEVELS OF DRUG CONTINUOUSLY FOLLOWING A SINGLE OFFICE-BASED INSERTION PROCEDURE. THE NON- BIODEGRADABLE SOLID MATRIX IMPLANT FORMULATION VIRTUALLY ELIMINATES THE RISK OF ACCIDENTAL DRUG DUMPING AND ASSOCIATED SERIOUS TOXICITY, AND ITS SUBDERMAL LOCATION ASSURES PATIENT COMPLIANCE FOR THE 6-MONTH TREATMENT DURATION. NALMEFENE HYDROCHLORIDE (NALMEFENE) IS AN OPIOID RECEPTOR ANTAGONIST APPROVED FOR THE MANAGEMENT AND REVERSAL OF OPIOID OVERDOSE, INCLUDING RESPIRATORY DEPRESSION. ITS ADVANTAGE OVER OTHER OPIOID ANTAGONISTS INCLUDES HIGHER POTENCY, LONGER HALF-LIFE, AND NO LIVER TOXICITY. PROTOTYPE NALMEFENE IMPLANTS INSERTED SUBDERMALLY IN RATS DELIVERED NALMEFENE CONTINUOUSLY FOR MONTHS WITHOUT ANY OBSERVABLE SAFETY CONCERNS. THE DATA SUGGESTS THAT ONE-THREE IMPLANTS COULD POTENTIALLY DELIVER SUFFICIENT DRUG TO PROVIDE UP TO 90% BLOCKAGE OF HUMAN BRAIN OPIOID RECEPTORS. SINCE NALMEFENE IS AN FDA APPROVED DRUG, AND BECAUSE TITAN'S IMPLANT TECHNOLOGY HAS BEEN VALIDATED IN AN APPROVED AND MARKETED PRODUCT FOR THE MAINTENANCE TREATMENT OF OUD, THE POTENTIAL REGULATORY RISK FOR DEVELOPING THIS PRODUCT IS RELATIVELY LOW. DEVELOPMENT COULD BE COST-EFFECTIVE AND THE PROBABILITY IS HIGH FOR SUCCESSFUL COMMERCIALIZATION OF THIS PRODUCT FOR THE PREVENTION OF RELAPSE TO OPIOID DEPENDENCE, FOLLOWING OPIOID DETOXIFICATION. THE OBJECTIVE IS TO DEVELOP A 6-MONTH IMPLANTABLE DEVICE THAT DELIVERS NALMEFENE AROUND THE CLOCK AT A STEADY RATE TO PREVENT RELAPSE TO OPIOID DEPENDENCE FOLLOWING OPIOID DETOXIFICATION. THE GOALS ARE TO MANUFACTURE NALMEFENE IMPLANTS, COMPLETE NONCLINICAL SAFETY AND PHARMACOLOGY STUDIES, AND CONDUCT CLINICAL STUDIES IN OUD SUBJECTS TO SUPPORT A NEW DRUG APPLICATION. THIS NOVEL PRODUCT COULD POTENTIALLY IMPROVE EFFECTIVENESS OF THE TREATMENT, ENHANCE COMPLIANCE, LOWER INDIVIDUAL AND SOCIETAL COSTS, AND SIGNIFICANTLY CONTRIBUTE TOWARDS ALLEVIATING THE DEADLY CONSEQUENCES OF THIS EPIDEMIC.

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FY10 FIXED GUIDEWAY PROJECT-VRE

ADJUVANT ENHANCED ANTIVIRAL IMMUNITY

FISCAL YEAR 5307 2020 OPERATING AND CAPITAL GRANT-LOW-NO

IMPROVE EXISTING AIRPORT

APPLICATION PURPOSE: THE PURPOSE OF THIS AWARD IS TO PROVIDE 1 YEAR OF OPERATING AND CAPITAL ASSISTANCE FOR THE MACATAWA AREA EXPRESS TRANSPORTATION AUTHORITY (MAX) TO ASSIST IT IN ITS 11 FIXED ROUTE AND COMPLIMENTARY PARATRANSIT TRANSIT OPERATIONS FACILITY UPGRADES AND IMPROVEMENTS ACQUISITION OF 1 OR MORE REVENUE VEHICLES ACQUISITION OF 1 OR MORE ADMINISTRATIVE VEHICLE COMPUTERS HARDWARE/SOFTWARE SUPPORT EQUIPMENT MISCELLANEOUS SUPPORT EQUIPMENT OFFICE EQUIPMENT AND MAINTENANCE EQUIPMENT.; ACTIVITIES PERFORMED: FUNDS WILL BE USED TO COVER ALL ELIGIBLE OPERATING EXPENSES SUCH AS DRIVER SALARIES FUEL ADMINISTRATIVE EXPENSES MAINTENANCE AND OTHER ELIGIBLE EXPENSES. FUNDS WILL INCLUDE THE ACQUISITION OF REVENUE VEHICLES ADMINISTRATIVE VEHICLE DESIGN AND RENOVATIONS OF FACILITIES PURCHASES OF OTHER NEEDED CAPITAL ASSETS.; EXPECTED OUTCOMES: FUNDING WILL ALLOW MAX TO CONTINUE TO PROVIDE OPERATIONS INCREASE AND IMPROVE THE RELIABILITY OF THE TRANSIT SERVICES UPGRADE FACILITIES THAT WILL ALLOW MAX TO PROVIDE BETTER SAFETY AND WORKING CONDITIONS FOR OUR EMPLOYEES RIDERS AND COMMUNITY.; INTENDED BENEFICIARIES: MACATAWA AREA COORDINATING COUNCIL MAX TRANSIT AND THE RIDERS THAT RELY ON ITS SERVICE WILL BENEFIT FROM CONTINUED SERVICES PERMITTING WORKERS AND OTHER RIDERS TO GET TO WORK AND OTHER DESTINATIONS. MAX EMPLOYEES WILL ALSO BENEFIT FROM SAFER AND MORE MODERN WORKING CONDITIONS.; SUBRECIPIENT ACTIVITIES: NONE

OPTIMIZATION OF THE PHARMACIST'S ROLE TO PREVENT AND CONTROL EMERGING AND RE-EMERGING INFECTIOUS DISEASE THREATS

DEVELOPMENT OF AN ANTI-P-SELECTIN ANTIBODY FOR THE TREATMENT OF SICKLE CELL DISEA

APPLICATION PURPOSE: THE PURPOSE OF THIS AWARD IS TO PROVIDE FUNDING FOR TRANSPORTATION DEMAND MANAGEMENT (TDM) PROJECTS AND THE PURCHASE OF EIGHT (8) BUS REPLACEMENTS.; ACTIVITIES PERFORMED: FUNDS WILL BE USED FOR BEST WORKPLACE PROGRAM MOBILE TICKETING MARKETING REVISING MAPS AND SCHEDULE BROCHURES ADVERTISING CAMPAIGNS AND WEBSITE SUPPORT. FUNDS WILL ALSO BE USED TO PURCHASE EIGHT (8) REPLACEMENT 45-FOOT COMMUTER BUSES MANUFACTURED IN 2008.; EXPECTED OUTCOMES: IMPROVED COMMUNICATIONS AND OUTREACH TO THE TRAVELING PUBLIC VIA ADVERTISING CAMPAIGNS WEBSITE MANAGEMENT AND UPDATED BROCHURES. MAINTAIN RELIABLE TRANSIT SERVICE AND PROVIDE MOBILITY THROUGHOUT THE PRTC SERVICE AREA.; INTENDED BENEFICIARIES: CITIZENS OF PRINCE WILLIAM COUNTY THE CITIES OF MANASSAS AND MANASSAS PARK AND THE TRAVELING PUBLIC IN THE PRTC SERVICE AREA.; SUBRECIPIENT ACTIVITIES: N/A

NOVEL CYCLIC BORONATE PENICILLIN BINDING PROTEIN INHIBITORS TO ELIMINATE THE THREAT POSED BY ?-LACTAMASES AND ENABLE A FUTURE TREATMENT OPTION FOR CARBAPENEM-RESISTANT ENTEROBACTERALES INFECTIONS - PROJECT SUMMARY CARBAPENEM-RESISTANCE IN ENTEROBACTERALES HAS STEADILY INCREASED OVER THE PAST DECADE, LEADING TO MULTIDRUG AND PAN-DRUG RESISTANCE (MDR/PDR), FURTHER EMPHASIZING THE NEED FOR NEW INNOVATIVE THERAPIES. CARBAPENEM- RESISTANT ENTEROBACTERALES (CRE) IS A SERIOUS GLOBAL HEALTH PROBLEM CLASSIFIED BY THE US CENTERS FOR DISEASE CONTROL AND PREVENTION AS AN “URGENT THREAT” AND BY THE WORLD HEALTH ORGANIZATION AS A “PRIORITY 1 CRITICAL THREAT”. THE SS-LACTAMS HAVE LONG BEEN THE FRONT LINE THERAPEUTIC OPTION FOR SUCH INFECTIONS, BUT EFFICACY OF THESE AGENTS, INCLUDING LAST RESORT CARBAPENEMS, IS THREATENED BY RECENT EXPANSION OF SS-LACTAMASES, PARTICULARLY SUBTYPES (E.G., NDM) SPREADING RAPIDLY AMONG ENTEROBACTERALES THAT ARE UNAFFECTED BY CLINICALLY-AVAILABLE SS-LACTAM/SS- LACTAMASE INHIBITOR COMBINATIONS. TO ADDRESS THE MEDICAL NEED, VENATORX HAS IDENTIFIED A NOVEL SERIES OF HIGHLY SELECTIVE CYCLIC BORONATES THAT BIND TO AND DISRUPT PENICILLIN-BINDING PROTEIN (PBP) TRANSPEPTIDASE (TPASE) FUNCTION WHILE AVOIDING THE ACTION OF ALL CURRENT AND FUTURE SS-LACTAMASES. THIS APPROACH CREATES THE FIRST PROSPECT AND “RARE” NEW CLASS GRAM NEGATIVE AGENT TO TREAT INFECTIONS CAUSED BY ANY SS-LACTAMASE-PRODUCING CRE PATHOGEN. SIGNIFICANT STRIDES IN MICROBIOLOGICAL ACTIVITY HAVE ALREADY BEEN ACHIEVED WITHIN THE SERIES BY THE LEAD COMPOUND VNRX-6736, WITH AN MIC90 OF 32 ΜG/ML RELATIVE TO 128 ΜG/ML FOR MEROPENEM-VABORBACTAM AND =1,024 ΜG/ML FOR CEFTAZIDIME-AVIBACTAM IN A RECENT CHALLENGE SET OF 100 CRE ISOLATES. NOT ONLY DOES VNRX- 6736 OUTPERFORM THESE CLINICAL COMPARATORS FROM AN MIC90 PERSPECTIVE, BUT DOES SO WITH A NARROW RANGE OF MIC OWING TO SS-LACTAMASE AVOIDANCE, A FEATURE THAT WILL ULTIMATELY BENEFIT SETTING OF BREAKPOINTS. THE SERIES IS RAPIDLY BACTERICIDAL, EXHIBITS A LOW SPONTANEOUS MUTATIONAL FREQUENCY (FREQUENCY OF RESISTANCE AT 4X MIC OF <2.7 X 10-11 IN E. COLI ATCC 25922) AND HAS FAVORABLE ADME AND PK PROPERTIES. PROOF OF CONCEPT EFFICACY HAS BEEN ACHIEVED BY VNRX-6736 IN THE MURINE THIGH MODEL OF CARBAPENEM-RESISTANT E. COLI INFECTION AND PHARMACOKINETICS MODELING SUGGESTS THAT 30-45% TIME ABOVE MIC IS REQUIRED TO ACHIEVE EFFICACY. OPTIMIZATION EFFORTS PROPOSED HEREIN ARE TARGETING AN 8-FOLD IMPROVEMENT IN ANTIBACTERIAL ACTIVITY DRIVEN BY RATIONAL STRUCTURE-GUIDED DESIGN TO IMPROVE PBP BINDING INTERACTION KINETICS TO ENABLE AN MIC90 = 4 ΜG/ML. SUCH AN OPTIMIZED CYCLIC BORONATE PBPI COULD BE A 1ST NEW CLASS ANTIBIOTIC ADDRESSING RESISTANCE TO SS-LACTAMS FOR THE TREATMENT OF INFECTIONS CAUSED BY CRE AND A LONG TERM THERAPEUTIC SOLUTION TO RESISTANCE DEVELOPMENT IN ENTEROBACTERALES.

THIS GRANT WILL RESTORE HABITAT IN PARTRIDGE CREEK COMMONS, MCBRIDE DRAIN, AND THE CLINTON RIVER SPILLWAY WITHIN THE CLINTON RIVER AREA OF CONCERN. C

MERRIMACK COLLEGE HIGHER EDUCATION EMERGENCY RELIEF FUND

NEW ASSISTANCE CA IN THE AMOUNT OF $1 270 000. THE TEC FOR THIS AGREEMENT IS $10 000 000.

STRENGTH THE GOP'S CAPACITY AND RESOURCES TO RESPOND TO THE COVID-19.

DEVELOPING TEIXOBACTIN FOR RESPIRATORY INFECTIONS - ABSTRACT: THE MAJOR GOAL OF THIS PROPOSAL IS TO INVESTIGATE THE POTENTIAL FOR TEIXOBACTIN, OUR NEWLY DISCOVERED ANTIBIOTIC, TO TREAT RESPIRATORY INFECTIONS. AS REPORTED IN 2019 BY THE CDC, PNEUMONIA CAUSED BY DRUG RESISTANT STREPTOCOCCUS PNEUMONIAE, AS WELL AS METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA), ARE CONSIDERED SERIOUS THREATS. IN ADDITION, RESPIRATORY BACTERIAL CO-INFECTIONS WITH COVID-19 HAVE RECENTLY BEEN RECOGNIZED AS A SIGNIFICANT PROBLEM. HAEMOPHILUS INFLUENZAE AND MORAXELLA CATARRHALIS ARE TWO OTHER RESPIRATORY PATHOGENS PARTICULARLY PROBLEMATIC IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ARE COMMON CAUSES OF COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA (CABP). THE MOST REMARKABLE, AND UNEXPECTED PROPERTY OF TEIXOBACTIN IS THE LACK OF ANY DETECTABLE RESISTANCE TO THIS COMPOUND. TEIXOBACTIN HITS TWO RELATED TARGETS—LIPID II, PRECURSOR OF PEPTIDOGLYCAN AND LIPID III, PRECURSOR OF WALL TEICHOIC ACID. THESE HIGHLY CONSERVED TARGETS ARE NOT MUTABLE—THEY ARE NOT PROTEINS AND ARE NOT DIRECTLY CODED BY DNA. SINCE OUR DISCOVERY OF TEIXOBACTIN, WE AND OTHERS HAVE FAILED TO GENERATE RESISTANT MUTANTS IN ANY SPECIES INCLUDING S. AUREUS, MYCOBACTERIUM TUBERCULOSIS OR BACILLUS ANTHRACIS. TEIXOBACTIN IS HIGHLY EFFICACIOUS IN ANIMAL MODELS OF THIGH, LUNG AND BLOOD INFECTIONS. ANIMAL INFECTION MODELS PREDICT THAT THE HUMAN DOSE OF TEIXOBACTIN FOR ACUTE SKIN AND SKIN STRUCTURE INFECTIONS (ABSSSI) WILL BE VERY LOW (=1 MG/KG/DAY), WHICH IS ADVANTAGEOUS, AS A LOW DOSE MAY MINIMIZE SIDE EFFECTS AND REDUCE MANUFACTURING COSTS. TEIXOBACTIN IS IN PRECLINICAL DEVELOPMENT AS AN INTRAVENOUS (IV) DRUG FOR TREATING SKIN INFECTIONS CAUSED BY PATHOGENS SUCH AS MRSA. A PRE-INVESTIGATIONAL NEW DRUG (IND) MEETING WITH FDA WAS HELD IN DECEMBER 2018 WHEREBY THE FDA GENERALLY AGREED WITH OUR DEVELOPMENT PLAN. AN IND SUBMISSION FOR ABSSSI IS PLANNED FOR 2022. IN THIS PROJECT, AIM 1 WILL PRODUCE ENOUGH TEIXOBACTIN FOR ALL THE PROPOSED STUDIES. AIM 2 WILL CONDUCT EFFICACY AND PK/PD STUDIES IN ANIMAL MODELS OF PNEUMONIA. AIM 3 WILL TEST IN VITRO SUSCEPTIBILITY, BACTERICIDAL ACTIVITY, POST ANTIBIOTIC EFFECT (PAE) AND RESISTANCE IN RECENT CLINICAL ISOLATES FROM RESPIRATORY INFECTIONS. AIM 4 WILL PREPARE AND SUBMIT AN IND APPLICATION FOR INTRAVENOUS TREATMENT OF A RESPIRATORY INFECTION. AIM 5 WILL EXPLORE ALTERNATIVE ROUTES OF TXB ADMINISTRATION (INHALATION AND INTRAMUSCULAR DELIVERY), WHICH WOULD BE PARTICULARLY USEFUL FOR OUTPATIENT TREATMENT OF RESPIRATORY AND OTHER INFECTIONS. WITH SUCCESSFUL COMPLETION OF THESE PROJECTS, WE WILL HAVE DEMONSTRATED THE PROMISE OF TEIXOBACTIN FOR TREATING DRUG RESISTANT RESPIRATORY INFECTIONS AND EXPLORED MORE CONVENIENT ROUTES OF TXB ADMINISTRATION.

APPLICATION PURPOSE: THIS IS A MERRIMACK VALLEY TRANSIT (MEVA) REQUEST FOR $6149420 IN CARRYOVER 5307 URBAN FORMULA FUNDS ($2778807 IN FY21 FUNDS AND $3370613 IN FY22 FUNDS) APPORTIONED TO THE BOSTON-MA-NH-RI UZA FOR A PROGRAM OF CAPITAL AND PLANNING PROJECTS NEEDED TO KEEP MEVA VEHICLES EQUIPMENT AND FACILITIES IN A STATE OF GOOD REPAIR AND OPTIMALLY SERVE THE CULTURALLY AND LINGUISTICALLY RICH MERRIMACK VALLEY COMMUNITIES WE OPERATE IN. THIS GRANT INCLUDES $1869570 OF MATCHING FUNDS FROM THE STATE INCLUDING $281772 OVERMATCH FOR ONE PROJECT AND $20000 FROM THE MERRIMACK VALLEY PLANNING COMMISSION.; ACTIVITIES PERFORMED: (1) ACQUISITION OF EIGHT (8) REPLACEMENT 35-FT BUSES: $3507520 IN FTA FUNDS ($4384400 TOTAL)(2) ENGINEERING AND ACQUISITION OF FOUR (4) STATE OF THE ART LOW FLOOR REPLACEMENT CUTAWAY VANS: $469620 IN FTA FUNDS ($939240 TOTAL)(3) SUPERVISORY VEHICLE REPLACEMENT: $40256 IN FTA FUNDS ($50326 TOTAL) (4) MISCELLANIES SUPPORT EQUIPMENT AND FACILITY REPAIR: $1360000 IN FTA FUNDS ($1700000 TOTAL) (5) IMPROVEMENTS TO MCGOVERN INTERMODAL TRANSPORTATION CENTER IN LAWRENCE MA: $640000 IN FTA FUNDS ($800000 TOTAL) (6) SHORT RANGE TRANSIT PLANNING GIS ROUTE MAPPING SERVICE AND OPERATIONS PLANNING AND BUS STOP SITING: $132000 IN FTA FUNDS ($165000 TOTAL); EXPECTED OUTCOMES: THIS PROGRAM OF CAPITAL AND PLANNING PROJECTS WILL ENABLE MEVA TO CONTINUE PROVIDING A RELIABLE RESPONSIVE AND SAFE SERVICE TO THE PUBLIC THAT WILL HELP KEEP EXISTING RIDERS AND ATTRACT NEW RIDERS BY KEEPING OUR VEHICLES EQUIPMENT AND FACILITIES IN A STATE OF GOOD REPAIR AND OPTIMIZING SERVICE IN ORDER TO FULLY RESPECT OUR RIDERS TIME AND PROVIDE THE COMMUNITIES WE SERVE WITH THE LEVEL OF TRANSIT SERVICE THEY NEED AND DESERVE.; INTENDED BENEFICIARIES: CONSISTENT WITH MEVAS MISSION TO PUT OUR CUSTOMERS FIRST THE PRIMARY BENEFICIARIES WILL BE TRANSIT RIDERS ACROSS THE MERRIMACK VALLEY. OUR SERVICE AREA DEPENDS ON QUALITY TRANSIT FOR CRITICALLY NEEDED ESSENTIAL TRAVEL TO WORK MEDICAL APPOINTMENTS EDUCATION TRAINING AND EVERYDAY LIFE. THE LARGEST CITY IN OUR SERVICE DISTRICT LAWRENCE IS 83% LATINO ACCORDING TO THE MOST RECENT CENSUS DATA AND HAS THE LOWEST PER CAPITA INCOME OF ANY MUNICIPALITY IN THE COMMONWEALTH OF MASSACHUSETTS. MEVAS SERVICE AREA WHICH ENCOMPASSES THE THE THREE GATEWAY CITIES OF LAWRENCE METHUEN AND HAVERHILL AS WELL AS AMESBURY AND NEWBURYPORT AND THE TOWNS OF ANDOVER NORTH ANDOVER BOXFORD GEORGETOWN GROVELAND MERRIMAC WEST NEWBURY SALISBURY NEWBURY ROWLEY AND NORTH READING HAS A POPULATION OF OVER 300000.; SUBRECIPIENT ACTIVITIES: NONE

INTERETHNIC INTEGRATION IN EDUCATION PROJECT (IIEP)

INTELLIGENT SYSTEMS

DEVELOPMENT OF ROR LIGANDS FOR TREATMENT OF CIRCADIAN RHYTHM DISORDERS

HOME INVESTMENT PARTNERSHIPS PROGRAM

BROAD-SPECTRUM, ORALLY BIOAVAILABLE BETA-LACTAMASE INHIBITORS FOR BIODEFENSE

A NOVEL AND HIGHLY SELECTIVE OREXIN 1 RECEPTOR ANTAGONIST FOR THE TREATMENT OF PATIENTS WITH OPIOID USE DISORDER. - PROJECT SUMMARY OPIOID USE DISORDER (OUD) IS A PUBLIC HEALTH CRISIS. CURRENT TREATMENTS SHOW LIMITED EFFICACY AND FAIL TO PREVENT RELAPSE TO DRUG USE DURING ATTEMPTED ABSTINENCE AND DRUG-OVERDOSE ARE ALL TOO FREQUENT. IN COLLABORATION WITH EOLAS THERAPEUTICS AND THE NIH BLUEPRINT NEUROTHERAPEUTICS NETWORK, ASTRAZENECA HAS DEVELOPED A POTENT AND SELECTIVE OX1 RECEPTOR ANTAGONIST (AZD4041/BPN-19302) WITH FAVORABLE DRUG-LIKE PHYSIOCHEMICAL PROPERTIES. SELECTIVE OX1 RECEPTOR ANTAGONISM BY AZD4041 REDUCES THE ADDICTION-RELEVANT BEHAVIORS IN RODENTS AND PRIMATES RELEVANT TO THOSE COMMONLY FOUND IN OPIOID USE DISORDER PATIENTS. SPECIFICALLY, AZD4041 REDUCED THE MOTIVATION TO CONSUME OPIOIDS (OR NICOTINE) AND ATTENUATED RELAPSE-LIKE DRUG SEEKING BEHAVIORS IN LABORATORY ANIMALS WHILE AVOIDING OX2 RECEPTOR-ASSOCIATED EFFECTS THAT COULD LIMIT ITS POTENTIAL AS A NOVEL TREATMENT FOR OUD (E.G., SLEEP-PROMOTING EFFECTS). AZD4041 DID NOT HAVE ANY NON-SPECIFIC BEHAVIORAL EFFECTS IN RODENTS OR PRIMATES. AZD4041 SHOWS FAVORABLE DRUG-LIKE SAFETY AND PHARMACOKINETIC (PK) PROFILES IN RATS AND DOGS. BASED ON THESE FINDINGS, WE INITIATED A PHASE 1 SINGLE ASCENDING DOSE SAFETY STUDY IN HEALTHY VOLUNTEERS (HV) (IND144437). TO DATE IN THIS TRIAL, AZD4041 HAS SHOWN A FAVORABLE PK AND SAFETY PROFILE IN HUMAN VOLUNTEERS AT EXPOSURES THAT ENCOMPASS THOSE PREDICTED TO HAVE EFFICACY IN OUD PATIENTS. IN THIS PROPOSAL, DURING THE UG3 PHASE, WE WILL CONDUCT THE MULTIPLE ASCENDING DOSE AND RESPIRATORY SAFETY ASSESSMENTS REQUIRED TO TEST THE COMPOUND IN OUD PATIENTS. CONTINGENT UPON THE SUCCESSFUL COMPLETION OF THE UG3 MILESTONES, WHICH INCLUDE FAVORABLE SAFETY, PK AND RESPIRATORY DEPRESSION PROFILES, WE WILL ADVANCE TO THE UH3 PHASE, DURING WHICH A PROOF OF CONCEPT EFFICACY STUDY WILL BE CONDUCTED IN PATIENTS SUFFERING FROM OUD. SUCCESSFUL COMPLETION OF THE UH3 PHASE WILL DELIVER A SELECTIVE OX1 RECEPTOR ANTAGONIST THAT IS READY TO ADVANCE TO LARGE-SCALE PHASE 2 AND 3 PIVOTAL EFFICACY STUDIES, BASED UPON WHICH ASTRAZENECA WILL MAKE THIS PROMISING AND HIGHLY BENEFICIAL THERAPEUTIC WIDELY AVAILABLE TO OUD PATIENTS.

DEVELOPMENT OF A SPLICE-SWITCHING ANTISENSE OLIGONUCLEOTIDE FOR THE TREATMENT OF SPINAL MUSCULAR ATROPHY

CONTRACT REDUCTION (CR) TO EVALUATE THE NEEDS AND CAPABILITIES OF THE SOUTHEAST MICHIGAN REGION (COUNTIES OF MACOMB, WAYNE, OAKLAND, LIVINGSTON, AND

PLANNING PM ADA

AN ANTIBODY IMMUNOPROTECTANT FOR CATEGORY B TOXINS

HISPANIC-SERVING INSTITUTIONS PROGRAM (STEM)

THIS IS A MERRIMACK VALLEY REGIONAL TRANSIT AUTHORITY (MVRTA) REQUEST FOR $5825882 IN AMERICAN RESCUE PLAN ACT (ARPA) FUNDS APPORTIONED TO THE BOSTON-MA-NH-RI UZA FOR OPERATING ASSISTANCE IN SUPPORT OF MVRTAS RECOVERY FROM THE IMPACTS THE COVID-10 PANDEMIC. PER THE PROVISIONS OF ARPA THE GRANT REQUESTS 100% FEDERAL SHARE AND ACTIVITIES INCLUDED IN THIS APPLICATION ARE NOT REQUIRED TO BE PROGRAMMED IN THE LONG-RANGE TRANSPORTATION PLAN OR STATEWIDE TRANSPORTATION IMPROVEMENT PROGRAM. MVRTA ALONG WITH ALL OTHER DESIGNATED RECIPIENTS IN THE BOSTON-MA-NH-RI UZA EXECUTED A SPLIT LETTER FOR ARPA FUNDING ON 5/25/21 (ATTACHED). THE GRANT WILL FUND OPERATING ASSISTANCE INCLUDING PREVENTIVE MAINTENANCE CORONAVIRUS HEALTH AND SAFETY PROTOCOLS AND PROMOTIONAL AND OUTREACH ACTIVITY IN SUPPORT OF REGAINING RIDERSHIP LOST DURING THE COVID-19 PANDEMIC. IN ACCORDANCE WITH FTA CIRCULAR 9030.1E PREVENTATIVE MAINTENANCE ACTIVITIES ARE CONSIDERED OPERATING COSTS. ACTIVITIES IN THIS GRANT BEGAN ON JANUARY 20 2020 AND WILL CONTINUE UNTIL THE PERIOD OF PERFORMANCE END DATE. MVRTA AGREES THAT IF IT RECEIVES FEDERAL FUNDING FROM THE FEDERAL EMERGENCY MANAGEMENT AGENCY (FEMA) OR THROUGH A PASS-THROUGH ENTITY THROUGH THE ROBERT T. STAFFORD DISASTER RELIEF AND EMERGENCY ASSISTANCE ACT A DIFFERENT FEDERAL AGENCY OR INSURANCE PROCEEDS FOR ANY PORTION OF A PROJECT ACTIVITY APPROVED FOR FTA FUNDING UNDER THIS GRANT AGREEMENT IT WILL PROVIDE WRITTEN NOTIFICATION TO FTA AND REIMBURSE FTA FOR ANY FEDERAL SHARE THAT DUPLICATES FUNDING PROVIDED BY FEMA ANOTHER FEDERAL AGENCY OR AN INSURANCE COMPANY.MVRTA SIGNED THE FY21 CERTIFICATIONS ASSURANCES IN TRAMS ON 1/19/21. AS THE FY22 CERTIFICATIONS ASSURANCES HAVE NOT YET BEEN PUBLISHED BY FTA THE FY21 CERTIFICATIONS ASSURANCES REMAIN IN EFFECT. MVRTA DUNS #090159711 HAS BEEN ENTERED INTO TRAMS. MVRTA IS CURRENT WITH ALL CIVIL RIGHTS SUBMISSIONS.

NRI-LARGE: TOWARD HUMANOID AVATAR ROBOTS FOR CO-EXPLORATION OF HAZARDOUS ENVIRONMENTS. WHILE SIGNIFICANT PROGRESS HAS BEEN MADE IN ROBOTICS, NO SYSTE

PURPOSE: REHABILITATE RUNWAY. THIS GRANT INCLUDES FUNDING 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 REHABILITATES 5,048 FEET OF RUNWAY 5/23 TO MAINTAIN THE STRUCTURAL INTEGRITY OF THE PAVEMENT AND TO MINIMIZE FOREIGN OBJECT DEBRIS. THIS GRANT FUNDS THE FIFTH PHASE OF CONSTRUCTION, WHICH CONSISTS OF BUILDING AN EMBANKMENT TO RAISE THE EXTENDED RUNWAY SAFETY AREA. INTENDED BENEFICIARY: THIS GRANT WILL PROVIDE FEDERAL FUNDING FOR AIRPORTS ASSOCIATED WITH WILEY FORD, MARYLAND.

HEAD START AND EARLY HEAD START

TOLERABILITY OF SRX246 IN HUNTINGTON'S DISEASE PATIENTS

SUFENTANILNANO TAB STUDY

YOUTH ETHNIC INTEGRATION ACTIVITY

CONSOLIDATED TRIBAL GOVERNMENT PROGRAM

DEVELOPMENT OF A SAFER AND MORE EFFECTIVE IBOGAINE ANALOG FOR THE TREATMENT OF OPIOID USE DISORDER - SUMMARY OPIOID USE DISORDER (OUD) CONTRIBUTES TO DISABILITY, LOSS OF WORK, AND OVER 100,000 OVERDOSE DEATHS PER YEAR IN THE U.S., EMPHASIZING THE CRITICAL NEED FOR NOVEL MEDICATIONS FOR OUD TREATMENT. IBOGAINE, A PSYCHOACTIVE ALKALOID FROM THE TABERNANTHE IBOGA SHRUB, HAS SHOWN PROMISE IN INTERRUPTING OPIOID DEPENDENCE, REDUCING WITHDRAWAL SYMPTOMS, AND INCREASING ABSTINENCE RATES, EVEN AFTER A SINGLE TREATMENT. HOWEVER, IBOGAINE'S CARDIOTOXICITY AND NEUROTOXICITY POSE SIGNIFICANT BARRIERS TO ITS DEVELOPMENT AS A DRUG. TO LEVERAGE IBOGAINE’S POTENTIAL AS AN OUD THERAPEUTIC AND ADDRESS THE RISKS TO PATIENT SAFETY, WE HAVE DEVELOPED A NEW CLASS OF SYNTHETIC IBOGA ALKALOIDS, NAMED “OXA-IBOGA”. THESE COMPOUNDS SHOW NO PRO-ARRHYTHMIC POTENTIAL, NO NEUROTOXIC EFFECTS, AND ENHANCED EFFICACY IN OUD-RELEVANT PRECLINICAL BEHAVIORAL ASSAYS COMPARED TO IBOGAINE. WE PROPOSE TO ADVANCE ONE OF THESE COMPOUNDS, GM-3009, INTO CLINICAL STUDIES BY ADVANCING GMP-MANUFACTURING AND FORMULATION OF GM-3009, COMPLETING IND-ENABLING TOXICITY STUDIES, AND DETERMINING THE EXPECTED THERAPEUTIC EXPOSURES OF GM-3009 AND TARGET ENGAGEMENT VIA TRANSLATIONAL BIOMARKERS. THESE STUDIES WILL COMPLETE THE UG3 PORTION OF THIS GRANT. IF SUCCESSFUL, THE PROPOSAL WILL ADVANCE TO THE UH3 PORTION, WHICH WILL CONDUCT FIRST-IN-HUMAN TRIALS, INCLUDING SAFETY AND TOLERABILITY STUDIES IN HEALTHY VOLUNTEERS (A SINGLE ASCENDING DOSE STUDY, SAD) AND A SAFETY STUDY WITH EXPLORATORY MEASURES OF EFFICACY IN OUD PATIENTS UNDERGOING OPIOID WITHDRAWAL. THE ENDPOINT OF THE ENTIRE PROJECT IS GENERATION OF CLINICAL SAFETY AND PRELIMINARY EFFICACY DATA TO SUPPORT SUBSEQUENT PHASE 2 EFFICACY STUDIES IN OUD. THE DEVELOPMENT OF GM-3009 BUILDS ON DECADES OF RESEARCH ON IBOGAINE AND HAS THE POTENTIAL TO DELIVER AN INNOVATIVE OUD THERAPY WITH RAPID AND LONG-TERM MITIGATION OF ACUTE AND PROTRACTED WITHDRAWAL SYMPTOMS AND CRAVINGS, WHICH LEAD TO NON-MEDICAL OPIOID USE.

AN IMMUNOPROTECTANT FOR ARGENTINE HEMORRHAGIC FEVER

IMPROVE EXISTING AIRPORT

MULTIDIMENSIONAL MODELING OF STRESS RESILIENCE FOR ROBUST SPACE FORCE GUARDIAN PERFORMANCE

IMPROVE EXISTING AIRPORT

A NOVEL AND HIGHLY SELECTIVE OREXIN 1 RECEPTOR ANTAGONIST FOR THE TREATMENT OF PATIENTS WITH OPIOID USE DISORDER. - PROJECT SUMMARY OPIOID USE DISORDER (OUD) IS A PUBLIC HEALTH CRISIS. CURRENT TREATMENTS SHOW LIMITED EFFICACY AND FAIL TO PREVENT RELAPSE TO DRUG USE DURING ATTEMPTED ABSTINENCE AND DRUG-OVERDOSE ARE ALL TOO FREQUENT. IN COLLABORATION WITH EOLAS THERAPEUTICS AND THE NIH BLUEPRINT NEUROTHERAPEUTICS NETWORK, ASTRAZENECA HAS DEVELOPED A POTENT AND SELECTIVE OX1 RECEPTOR ANTAGONIST (AZD4041/BPN-19302) WITH FAVORABLE DRUG-LIKE PHYSIOCHEMICAL PROPERTIES. SELECTIVE OX1 RECEPTOR ANTAGONISM BY AZD4041 REDUCES THE ADDICTION-RELEVANT BEHAVIORS IN RODENTS AND PRIMATES RELEVANT TO THOSE COMMONLY FOUND IN OPIOID USE DISORDER PATIENTS. SPECIFICALLY, AZD4041 REDUCED THE MOTIVATION TO CONSUME OPIOIDS (OR NICOTINE) AND ATTENUATED RELAPSE-LIKE DRUG SEEKING BEHAVIORS IN LABORATORY ANIMALS WHILE AVOIDING OX2 RECEPTOR-ASSOCIATED EFFECTS THAT COULD LIMIT ITS POTENTIAL AS A NOVEL TREATMENT FOR OUD (E.G., SLEEP-PROMOTING EFFECTS). AZD4041 DID NOT HAVE ANY NON-SPECIFIC BEHAVIORAL EFFECTS IN RODENTS OR PRIMATES. AZD4041 SHOWS FAVORABLE DRUG-LIKE SAFETY AND PHARMACOKINETIC (PK) PROFILES IN RATS AND DOGS. BASED ON THESE FINDINGS, WE INITIATED A PHASE 1 SINGLE ASCENDING DOSE SAFETY STUDY IN HEALTHY VOLUNTEERS (HV) (IND144437). TO DATE IN THIS TRIAL, AZD4041 HAS SHOWN A FAVORABLE PK AND SAFETY PROFILE IN HUMAN VOLUNTEERS AT EXPOSURES THAT ENCOMPASS THOSE PREDICTED TO HAVE EFFICACY IN OUD PATIENTS. IN THIS PROPOSAL, DURING THE UG3 PHASE, WE WILL CONDUCT THE MULTIPLE ASCENDING DOSE AND RESPIRATORY SAFETY ASSESSMENTS REQUIRED TO TEST THE COMPOUND IN OUD PATIENTS. CONTINGENT UPON THE SUCCESSFUL COMPLETION OF THE UG3 MILESTONES, WHICH INCLUDE FAVORABLE SAFETY, PK AND RESPIRATORY DEPRESSION PROFILES, WE WILL ADVANCE TO THE UH3 PHASE, DURING WHICH A PROOF OF CONCEPT EFFICACY STUDY WILL BE CONDUCTED IN PATIENTS SUFFERING FROM OUD. SUCCESSFUL COMPLETION OF THE UH3 PHASE WILL DELIVER A SELECTIVE OX1 RECEPTOR ANTAGONIST THAT IS READY TO ADVANCE TO LARGE-SCALE PHASE 2 AND 3 PIVOTAL EFFICACY STUDIES, BASED UPON WHICH ASTRAZENECA WILL MAKE THIS PROMISING AND HIGHLY BENEFICIAL THERAPEUTIC WIDELY AVAILABLE TO OUD PATIENTS.

DEVELOPMENT OF TP-317 FOR THE INDUCTION AND MAINTENANCE OF REMISSION IN ULCERATIVE COLITIS PATIENTS

APPLICATION PURPOSE: THE PURPOSE OF THIS AWARD IS TO PROVIDE OPERATIONAL FUNDING FOR MEVA TO SUPPORT FIXED ROUTE/COMPLEMENTARY ADA TRANSIT SERVICES AS WELL AS PREVENTATIVE MAINTENANCE ACTIVITIES.; ACTIVITIES PERFORMED: ACTIVITIES TO BE PERFORMED: OPERATING ASSISTANCE: $739365 IN FTA FUNDS ($1478730 TOTAL) PREVENTIVE MAINTENANCE: $2984400 IN FTA FUNDS ($3730500 TOTAL)ADA OPERATING ASSISTANCE: $1488880 IN FTA FUNDS ($1861100 TOTAL); EXPECTED OUTCOMES: THIS PROGRAM OF VARIOUS OPERATING ACTIVITIES WILL ENABLE THE MEVA TO CONTINUE PROVIDING A RELIABLE RESPONSIVE AND SAFE SERVICE TO THE PUBLIC THAT WILL HELP KEEP EXISTING RIDERS AND ATTRACT NEW RIDERS.; INTENDED BENEFICIARIES: RIDERS IN MEVAS SERVICE AREA WHICH ENCOMPASSES THE CITIES OF LAWRENCE METHUEN HAVERHILL AMESBURY AND NEWBURYPORT AND THE TOWNS OF ANDOVER NORTH ANDOVER BOXFORD GEORGETOWN GROVELAND MERRIMAC WEST NEWBURY SALISBURY NEWBURY ROWLEY AND NORTH READING WITH AN APPROXIMATE POPULATION OF 300000.; SUBRECIPIENT ACTIVITIES: N/A

DEVELOPMENT OF TNX-1300 (DOUBLE MUTANT COCAINE ESTERASE) FOR THE TREATMENT OF LIFE-THREATENING COCAINE INTOXICATION - PROJECT SUMMARY/ABSTRACT IN THE UNITED STATES, RECREATIONAL COCAINE USE CONTINUES TO REPRESENT A SIGNIFICANT PUBLIC HEALTH CONCERN. IN 2018, AN ESTIMATED 5.5 MILLION PEOPLE RECREATIONALLY SELF-ADMINISTERED COCAINE BY INSUFFLATION, INHALATION, OR INJECTION. MANY OF THESE INDIVIDUALS ARE AT RISK OF SUCCUMBING TO ACUTE COCAINE INTOXICATION, A CONDITION IN WHICH LIFE-THREATENING CARDIOVASCULAR AND NEUROLOGICAL SYMPTOMS ARE EXPERIENCED. THE CURRENT STANDARD OF CARE CONSISTS PRIMARILY OF SUPPORTIVE ACUTE CARE DIRECTED AT THE SPECIFIC SYMPTOMS EXPRESSED BY INDIVIDUAL PATIENTS. DESPITE THE SIGNIFICANT UNMET MEDICAL NEED, NO PHARMACOTHERAPIES ARE APPROVED FOR TREATING COCAINE TOXICITY IN THE ACUTE CARE SETTING. THE DEVELOPMENT OF A TREATMENT THAT ADDRESSES THE ROOT CAUSE OF COCAINE INTOXICATION (I.E., CIRCULATING COCAINE AND ITS ACTIVE METABOLITES), WOULD ALLOW CLINICIANS TO PROVIDE A POTENTIALLY FASTER AND SAFER INTERVENTION IN THE ACUTE CARE SETTING. FURTHERMORE, BY DIRECTLY REMOVING THE TOXIC OFFENDING AGENT FROM THE SYSTEMIC CIRCULATION, SUCH A TREATMENT COULD MORE EFFECTIVELY AND COMPREHENSIVELY ADDRESS THE MULTIPLE MEDICAL RISKS AND SEQUELAE OF COCAINE INTOXICATION. TO FULFILL THIS UNMET NEED, TONIX IS DEVELOPING TNX-1300, A MUTANT RECOMBINANT BACTERIAL COCAINE ESTERASE (COCE) THAT HAS BEEN SHOWN IN A PILOT PHASE 2 CLINICAL LABORATORY STUDY TO METABOLIZE AND REDUCE BY ~90% SYSTEMIC COCAINE LEVELS WITHIN 2 MINUTES OF A SINGLE INTRAVENOUS ADMINISTRATION. IN THIS U01 APPLICATION, TONIX PROPOSES TO ADVANCE THE TNX-1300 DEVELOPMENT PROGRAM VIA THE FOLLOWING SPECIFIC AIMS: 1. CONDUCT A PHASE 2 PROOF-OF-CONCEPT RANDOMIZED TRIAL OF PATIENTS PRESENTING TO EMERGENCY DEPARTMENT SITES IN A STATE OF COCAINE INTOXICATION; 2. OPTIMIZE CMC PRODUCTION OF A GMP DRUG PRODUCT BATCH FOR USE IN PHASE 2 AND 3 TRIALS, INCLUDING A LYOPHILIZATION CYCLE; 3. FACILITATE COMPLETION OF REGULATORY MILESTONES, IN PARTICULAR THE PREPARATION AND EXECUTION OF AN END OF PHASE 2 MEETING WITH FDA; AND 4. A COMMERCIALIZATION PROGRAM WITH KEY OPINION LEADER DEVELOPMENT, TARGET PRODUCT PROFILE TESTING, AND MARKET RESEARCH WITH PHYSICIANS, PAYERS AND PATIENTS, TO INFORM THE DESIGN OF A FUTURE PHASE 3 THAT WILL BE FULLY DEVELOPED AND DESIGNED IN YEAR 3 OF THIS PROGRAM. SUCCESSFULLY ACHIEVING THE MILESTONES OUTLINED IN THIS PROPOSAL WOULD SUBSTANTIALLY ADVANCE THIS NOVEL TREATMENT APPROACH TO THE STAGE OF PHASE 3 PIVOTAL TESTING REQUISITE FOR THE NEW DRUG APPLICATION AND MARKETING APPROVAL.

CLINICAL DEVELOPMENT A THERAPEUTIC AGENT FOR COPD

COOPERATIVE AGREEMENT WITH CIRD TO PROMOTE CITIZEN ADVOCACY OVERSIGHT AND SUPPORT TO PROMOTE TRANSPARENCY AND ANTI-CORRUPTIONS REFORMS.

DEVELOPMENT OF AN ALDH2-TARGETING RNAI THERAPEUTIC FOR ALCOHOL USE DISORDERS

ROUTES TOWARDS INTEGRATION IN PERU

ACCELERATION OF THE DEVELOPMENT AND USE OF INNOVATIVE, CROSS CUTTING ADDITIVE MANUFACTURING MEASUREMENT SCIENCE TECHNOLOGIES IN THE UNITED STATES

SUPPORTIVE HOUSING FOR THE ELDERLY

HBI-002 TO PREVENT VASO-OCCLUSIVE CRISES IN SICKLE CELL DISEASE

RECOVERY ACT GREEN JOBS

BIASED AGONISM IN GPCR DRUG DISCOVERY: APPLICATION TO SOMATOSTATIN AGONISTS

IND-ENABLING PRECLINICAL DEVELOPMENT OF A SUSTAINED-RELEASE PRITELIVIR INTRAVAGINAL RING FOR THE TREATMENT AND PROPHYLAXIS OF GENITAL HERPES IN WOMEN

INDIAN HOUSING BLOCK GRANTS

APPLICATION PURPOSE: THE PURPOSE OF THIS AWARD IS TO PROVIDE OPERATIONAL FUNDING FOR MEVA TO SUPPORT FIXED ROUTE BUS COMPLEMENTARY ADA TRANSIT SERVICES AS WELL AS PREVENTATIVE MAINTENANCE ACTIVITIES.; ACTIVITIES PERFORMED: ACTIVITIES TO BE PERFORMED: OPERATING ASSISTANCE: $755100 IN FTA FUNDS ($1510200 TOTAL) PREVENTIVE MAINTENANCE: $2400000 IN FTA FUNDS ($3000000 TOTAL)ADA OPERATING ASSISTANCE: $1657600 IN FTA FUNDS ($2072000 TOTAL); EXPECTED OUTCOMES: THIS PROGRAM OF VARIOUS OPERATING ACTIVITIES WILL ENABLE THE MEVA TO CONTINUE PROVIDING A RELIABLE RESPONSIVE AND SAFE SERVICE TO THE PUBLIC THAT WILL HELP KEEP EXISTING RIDERS AND ATTRACT NEW RIDERS.; INTENDED BENEFICIARIES: RIDERS IN MEVAAS SERVICE AREA WHICH ENCOMPASSES THE CITIES OF LAWRENCE METHUEN HAVERHILL AMESBURY AND NEWBURYPORT AND THE TOWNS OF ANDOVER NORTH ANDOVER BOXFORD GEORGETOWN GROVELAND MERRIMAC WEST NEWBURY SALISBURY NEWBURY ROWLEY AND NORTH READING WITH AN APPROXIMATE POPULATION OF 300000.; SUBRECIPIENT ACTIVITIES: N/A

CAPITAL AND MANAGEMENT ACTIVITIES (FORMULA)

CRAFT - CHARACTERIZING REALISTIC ARCHITECTURES FOR FAULT-TOLERANCE

ACCOMACK-NORTHAMPTON PLANNING DISTRICT COMMISSION, VA; EASTERN SHORE OF VIRGINIA RAIL TRAIL UNDER THE REBUILDING AMERICAN INFRASTRUCTURE WITH SUSTAINABILITY AND EQUITY PROGRAM.

FFY18 FLEX FUNDS FOR BUS PROJECTS

PURCHASE NEW BUSES & AUTOMATED FARE