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COVID-19 DPA3 "DEVELOPMENT OF LARGE FORGING CAPABILITIES IN SUPPORT OF NAVY PROGRAM"

PHASE II RANDOMIZED CONTROLLED TRIAL OF BENFOTIAMINE IN EARLY ALZHEIMER'S DISEASE - WE PROPOSE A SEAMLESS PHASE 2A-2B TRIAL INVESTIGATING BENFOTIAMINE, A PRODRUG OF THIAMINE, AS A FIRST-IN- CLASS SMALL MOLECULE TREATMENT FOR EARLY ALZHEIMER'S DISEASE (AD). WE CALL THIS PROPOSED TRIAL `BENFOTIAMINE IN EARLY ALZHEIMER'S DISEASE (BEAD)”. BRAIN TISSUE THIAMINE DEFICIENCY CAUSES MEMORY DEFICITS THAT ARE REVERSIBLE WITH THIAMINE TREATMENT IN PRECLINICAL AD MODELS AND IN HUMAN CONDITIONS INCLUDING WERNICKE KORSAKOFF SYNDROME. IN ANIMAL MODELS OF MILD IMPAIRMENT OF OXIDATIVE METABOLISM (I.E., THIAMINE DEFICIENCY), NEURONAL LOSS IS ACCOMPANIED BY CHANGES IN NEUROFILAMENT LIGHT (NFL), BY INCREASED NEUROINFLAMMATION (GLIAL FIBRILLARY ACID PROTEIN GFAP), BY ELEVATION OF ADVANCED GLYCATION END PRODUCTS (AGE) AND BY INCREASED PLAQUE AND BY TANGLE PATHOLOGY, ALL OF WHICH OCCUR IN AD. BENFOTIAMINE DRAMATICALLY RAISES BLOOD AND BRAIN TISSUE THIAMINE IN THESE MODELS, CONFERRING BEHAVIORAL BENEFIT AND REDUCED PLAQUE AND TANGLE FORMATION. WE PREVIOUSLY CONDUCTED AN EARLY PHASE 2 PILOT SINGLE-SITE 12-MONTH DOUBLE BLIND PLACEBO CONTROLLED RCT OF 600 MG OF BENFOTIAMINE IN 71 PERSONS WITH EARLY AD. BENFOTIAMINE WAS WELL TOLERATED, HAD ENCOURAGING PHARMACOKINETIC (PK) AND PHARMACODYNAMIC (PD) RESPONSES AND SHOWED BENEFITS ON THE CLINICAL DEMENTIA RATING (CDR), THE ADAS-COG, AND MARKERS OF BRAIN METABOLISM. THERE IS NEW EVIDENCE IN MICE THAT A 1200 MG OF BENFOTIAMINE FURTHER INCREASES THIAMINE LEVELS WITH GREATER COGNITIVE BENEFITS. THUS, WE ARE PROPOSING AN 18-MONTH PHASE 2A/2B RANDOMIZED PLACEBO CONTROLLED RCT OF BENFOTIAMINE TESTING 600 MG/DAY AND 1200 MG/DAY IN 400 PARTICIPANTS EARLY AD, INCLUDING MILD COGNITIVE IMPAIRMENT (MCI) AND MILD DEMENTIA WITH PLASMA EVIDENCE OF AMYLOID POSITIVITY. OUR OVERARCHING HYPOTHESIS IS THAT SIGNIFICANT BENEFITS IN COGNITION AND GLOBAL FUNCTION WILL OCCUR WITH DOSES OF BENFOTIAMINE THAT ARE SAFE, WELL TOLERATED, AND ACHIEVE SUFFICIENT TARGET ENGAGEMENT. IF THIS PHASE 2 TRIAL IS SUCCESSFUL WE HAVE A CONSOLIDATED SEAMLESS PHASE 3 DEVELOPMENT PLAN TO EXPEDITE BENFOTIAMINE REACHING PATIENTS. WE WILL TEST OUR OVERARCHING HYPOTHESIS THROUGH THE FOLLOWING AIMS:(1) TO EFFICIENTLY DETERMINE THE HIGHEST SAFE AND WELL-TOLERATED DOSE OF BENFOTIAMINE IN PHASE 2A (600 MG OR 1200 MG) THAT CAN BE ADVANCED TO LONG TERM CLINICAL ENDPOINTS AT 72 WEEKS; (2) TO EVALUATE THE EFFICACY OF BENFOTIAMINE IN PHASE 2B, TO BENEFIT (A) GLOBAL FUNCTION MEASURED WITH THE CDR SUM OF BOXES (CDR-SB) AND (B) COGNITION MEASURED WITH ADAS-COG13 DURING A TREATMENT PERIOD OF 72 WEEKS IN EARLY AD; (3) TO EVALUATE THE PK (SERUM THIAMINE AND IT'S ESTERS) AND PD EFFECTS (THIAMINE PYROPHOSPHATE ACTIVATION OF TRANSKETOLASE AND ADVANCED GLYCATION END-PRODUCTS (AGES)) OF BENFOTIAMINE, AND THEIR RELATION TO THE PRIMARY OUTCOMES; (4) TO EVALUATE THE DOWNSTREAM BIOLOGICAL EFFECTS OF TREATMENT WITH BENFOTIAMINE IN EARLY AD ON MEASURES OF NEURODEGENERATION (CORTICAL THICKNESS ON MRI, PLASMA NEUROFILAMENT LIGHT AND TOTAL TAU), NEUROINFLAMMATION (GLIAL FIBRILLARY ACID PROTEIN) AND AD PATHOPHYSIOLOGY INCLUDING P-TAU 231, AND ASS 42/40 RATIO.

MITOCHONDRIAL DYSFUNCTION IN NEUROGEGENERATION OF AGING

A MOLECULAR FRAMEWORK FOR UNDERSTANDING DCIS

THE EFFECT OF PEPTIDE THERAPY AND ALLERGEN PROVOCATION ON FEL D1-SPECIFIC T CELLS

ONE YEAR DAY-AND-NIGHT HOME CLOSED LOOP IN YOUNG PEOPLE WITH TYPE 1 DIABETES

NEURAL PREDICTORS OF HAND THERAPY EFFICACY IN CHILDREN WITH CEREBRAL PALSY

UNDERSTANDING TUMOR DORMANCY AS A MEANS OF SECONDARY PREVENTION

PLASTICITY IN THE AGING OLFACTORY SYSTEM

SYNAPSE ELIMINATION IN THE CENTRAL NERVOUS SYSTEM

USING MULTI-MODAL DATA INTEGRATION ACROSS BREAST CANCER MOLECULAR SUBTYPES TO DEVELOP PREDICTORS OF TREATMENT RESPONSE, EARLY RELAPSE, AND SURVIVAL AND TO EXPLORE EARLY SIGNALS OF LATER METASTATIC RECURRENCE

THE NOMENCLATURE OF HUMAN AND VERTEBRATE GENES

MECHANISTIC LINKS BETWEEN THE BENEFITS OF PHARMACOLOGICALLY HIGH THIAMINE (VITAMIN B1) IN ALZHEIMER'S DISEASE TO ADVANCED GLYCATION ENDPRODUCTS (AGE) - EXPERIMENTAL DATA LINKING THIAMINE (VITAMIN B1) DEFICIENCY TO ALZHEIMER’S DISEASE (AD) INSPIRED OUR CLINICAL TRIAL, WHICH GENERATED PRELIMINARY EVIDENCE THAT PHARMACOLOGICAL THIAMINE PRODUCED BY THE DRUG BENFOTIAMINE PROVIDES CLINICAL BENEFIT. WE HYPOTHESIZE THAT PHARMACOLOGICAL THIAMINE IS PROTECTIVE BY DIMINISHING THE FORMATION OF ADVANCED GLYCATION ENDPRODUCTS (AGE). AGE ARE PROTEINS AND LIPIDS THAT BECOME GLYCATED AND HARMFUL FOLLOWING EXPOSURE TO REDUCING SUGARS. AGE CAUSE IRREVERSIBLE DAMAGE TO BIOLOGICAL MACROMOLECULES BY ALTERING THEIR STRUCTURAL AND FUNCTIONAL INTEGRITY. ABUNDANT EVIDENCE LINKS AGE TO AD. IN AD ANIMAL MODELS, THIAMINE DEFICIENCY INCREASES AGE AND EXACERBATES PLAQUES AND TANGLE FORMATION, WHILE INCREASED THIAMINE DIMINISHES AGE AND PATHOLOGY. IN OUR PILOT CLINICAL TRIAL, PHARMACOLOGICAL THIAMINE LEVELS DIMINISHED GLOBAL PLASMA AGE LEVELS AND IMPROVED SYMPTOMS IN PATIENTS WITH AD. INTERESTINGLY, IN AD PATIENTS, THE EFFECTS OF HIGH THIAMINE ARE DIMINISHED IN PATIENTS CARRYING THE APOE4 GENOTYPE, THE MOST SIGNIFICANT GENETIC RISK FACTOR FOR SPORADIC AD. WE POSTULATE THAT THIS IS BECAUSE APOE4 INCREASES UNIQUE AGE AT EARLIER STAGES. OPTIMIZING THIS THERAPEUTIC APPROACH REQUIRES A BETTER UNDERSTANDING OF THE MECHANISM UNDERLYING THE ACTION OF BENFOTIAMINE. ALL PREVIOUS RELATED AD AND THIAMINE STUDIES HAVE UTILIZED AGE ANTIBODY SURVEYS. THIS DATA IS LIMITED TO A SMALL RANGE OF AGE AND PROVIDES NO DATA ON THE PROTEINS AND SPECIFIC SITES MODIFIED WITH GLYCATION. WE WILL PROVIDE THIS CRITICAL DATA BY USING MULTIPLE STATE-OF-THE-ART MASS SPECTROMETRIC MEASURES OF AGE. GLOBAL GLYCAPROTEOMICS WILL IDENTIFY GLYCATED PROTEINS AND SPECIFIC SITES OF AGE MODIFICATIONS AND AGE- OMICS WILL IDENTIFY A BROAD RANGE OF CROSSLINKING AND NON-CROSSLINKING AGE. A SECOND MAJOR GAP IS THE LACK OF OUR UNDERSTANDING ON HOW APOE4 MODIFIES THE RESPONSE TO THIAMINE. NOVEL APOE3 AND APOE4 HUMANIZED APP MOUSE MODELS WILL ALLOW US TO TEST THESE INTERACTIONS. WE WILL TEST OUR HYPOTHESES: (1) IN AD AUTOPSY BRAINS AT DIFFERENT STAGES OF THE DISEASE, AGE MODIFICATIONS ARE CRITICAL TO THE PATHOPHYSIOLOGY OF AD IN AN APOE-DEPENDENT MANNER. (2) IN MOUSE MODELS OF AD, THIAMINE DEFICIENCY DRIVES AD-LIKE PATHOLOGY AND MEMORY LOSS BY CAUSING SPECIFIC BRAIN AND BLOOD AGE MODIFICATIONS WHICH ARE MODIFIED BY APOE GENOTYPE. (3) IN MOUSE MODELS, BENFOTIAMINE IS BENEFICIAL BY DIMINISHING SPECIFIC AGE AND THE TREATMENT MUST BE INITIATED AT AN EARLIER STAGE OF DISEASE IN APOE4 MICE. THESE STUDIES WILL DRAMATICALLY IMPROVE OUR UNDERSTANDING OF THE ROLE OF AGE IN AD AND ITS LINK TO A TREATMENT OF PHARMACOLOGICAL THIAMINE LEVELS. DEFINING THE INTERACTION OF AGE AND THIAMINE IN THE ETIOLOGY AND PROGRESSION OF AD WILL ENABLE THE DEVELOPMENT OF SPECIFIC AGE SIGNATURES FOR TARGETS OF ENGAGEMENT FOR THERAPEUTIC TRIALS AND AS AD DIAGNOSTIC AND PROGNOSTIC BIOMARKERS. THESE STUDIES WILL DEFINE THE DIFFERENTIAL EFFECTIVENESS OF THIAMINE BY APOE GENOTYPE AND DEFINE THE MOST EFFECTIVE THERAPEUTIC APPROACH FOR APOE3 AND CONSISTENTLY HARD TO TREAT APOE4 CARRIERS. WE THEREFORE EXPECT THIS STUDY WILL HAVE A HIGH IMPACT ON TRANSLATIONAL AD MEDICINE.

THE ROLE OF CD36 IN ISCHEMIC INFLAMMATION AND INJURY

CORTICOSPINAL NEURON DYSFUNCTION AND DEGENERATION IN ALS: TESTING THE ROLE OF CORTICOMOTOR CONNECTIVITY IN MOTOR NEURON DISEASE - ABSTRACT (SUMMARY): IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS (ALS) AND THE RELATED MOTOR NEURON DISEASE (MND) PRIMARY LATERAL SCLEROSIS (PLS), DEFICITS IN MOTOR CONTROL OCCUR AS A CONSEQUENCE OF THE DEGENERATION OF CORTICOSPINAL NEURONS (CSNS). ALS IS MORE COMMON THAN PLS, AND GENETICALLY MORE COMPLEX, WITH FAMILIAL FORMS ASSOCIATED WITH CAUSAL MUTATIONS IN OVER 30 ALS-RELATED GENES. IN THESE ALS MICE, HOWEVER, DYSFUNCTION AND DEGENERATION OF CSNS HAVE NOT BEEN CAREFULLY EXAMINED, AND DATA IMPLICATING CORTICOSPINAL (CS) CIRCUITS IN THESE MODEL SYSTEMS OF ALS IS SURPRISINGLY LIMITED. ONE REASON FOR THIS MAY BE THE VERY DIFFERENT PATTERN OF CONNECTIVITY BETWEEN CSNS AND SPINAL MNS IN HUMANS VS. MICE. IN HUMANS, CS AXONS LOCATED IN THE VENTRAL AND LATERAL FUNICULI FORM DIRECT CONNECTIONS WITH BOTH MNS (CORTICO-MOTONEURONAL (CM) CONNECTIONS) AND INTERNEURONS. IN CONTRAST, CS AXONS IN MICE ARE LOCATED MAINLY IN THE DORSAL FUNICULUS AND ONLY FORM INDIRECT CONNECTIONS WITH MNS THROUGH PRE-MOTOR INTERNEURONS. THEREFORE, WE WILL USE PLEXINA1 MUTANT MICE WHICH HAVE CM CONNECTIONS TOGETHER WITH ALS MOUSE MODELS TO ANALYZE CS CIRCUITS. OUR CENTRAL HYPOTHESIS IS THAT PROGRESSIVE DEFECTS IN CS CIRCUITRY IN ALS MICE WILL BE EXACERBATED BY THE ESTABLISHMENT OF CM CONNECTIONS. IN AIM 1, WE WILL DETERMINE FORMATION OF CS CIRCUITS IN ALS MOUSE MODELS WITH CM CONNECTIONS. IN AIM 2, WE WILL DETERMINE FUNCTION OF CS CIRCUITS IN ALS MOUSE MODELS WITH CM CONNECTIONS. IN AIM 3, WE WILL EXAMINE SKILLED MOVEMENTS IN ALS MOUSE MODELS WITH CM CONNECTIONS. THESE STUDIES WILL PROVIDE A MODEL SYSTEM TO STUDY MECHANISMS OF CS DEGENERATION IN ALS/PLS, AND TO TEST NOVEL THERAPEUTICS TARGETING UPPER MOTOR NEURON DYSFUNCTION IN THESE DISORDERS.

TRANSCRANIAL DIRECT CURRENT STIMULATION AND ROBOTIC TRAINING IN CHRONIC STROKE

ENGAGING NEURON-INTRINSIC SIGNALING FOR AXON GROWTH AFTER SPINAL CORD INJURY

GRADING VISUAL IMPAIRMENT IN CHILDREN WITH BRAIN INJURY

POWER PROJECTION AND SUBVERSION VIA MALIGN INFLUENCE CAMPAIGNS ON SOCIAL MEDIA: COMPARING EFFECTS OF COGNITIVE BIASES AND CULTURAL VALUES ON INFORMATI

HIGHER EDUCATION EMERGENCY RELIEF FUND-INSTITUTIONAL PORTION

DISSECTING SPINAL INTERNEURON CIRCUITS TO CONTROL SKILLED MOVEMENTS

ROLE OF AP-2BETA IN ANTERIOR SEGMENT DEVELOPMENT

EXTENDING INTERMINE TO YEAST RAT AND ZEBRAFISH MODEL ORGANISM DATABASES

MODULATION OF CORTICAL NETWORKS, A NEW APPROACH TO SPINAL CORD INJURY REHABILITATION

IMMUNE-MEDIATED MECHANISMS UNDERLYING CONDITIONING-INDUCED STROKE RECOVERY

HOST RESPONSES TO MYCOBACTERIUM INFECTION IN ZEBRAFISH

HOST-RESPONSES TO MYCOBACTERIUM INFECTION IN ZEBRAFISH

VASCULAR CONTROL IN DIABETIC RETINOPATHY

PRECLINICAL STUDIES ON POLYUNSATURATED FATTY ACID-TAXOID CONJUGATE FOR IND FILING

AN INVESTIGATION OF RADIAL GLIA AS THE SOURCE OF EPENDYMOMA STEM CELLS

INTEGRATING MEASUREMENTS OF IMMUNE ESCAPE AND IN VITRO REPLICATION WITH COMPUTATIONAL MODELS TO UNDERSTAND AND PREDICT THE ANTIGENIC EVOLUTION OF SEASONAL A/H3N2 INFLUENZA VIRUSES - PROJECT SUMMARY SEASONAL INFLUENZA VIRUS VACCINES HAVE TO BE REFORMULATED MOST YEARS PRIMARILY DUE TO IMMUNE ESCAPE CAUSED BY MUTATIONS IN THE SURFACE HEMAGGLUTININ (HA) PROTEIN. THE GENETIC VARIATION IN HA ONLY OCCASIONALLY CAUSES CHANGE IN ANTIGENIC PHENOTYPE AND CONSEQUENT IMMUNE ESCAPE. FOR EXTENDED PERIODS OF TIME STRAINS WITH GENETIC DIFFERENCES REMAIN IN A SINGLE ANTIGENIC CLUSTER. IN 2013 WE (KOEL ET AL.)1 FOUND THAT THE AMINO ACID SUBSTITUTIONS RESPONSIBLE FOR ANTIGENIC CLUSTER TRANSITIONS IN HUMAN A/H3N2 VIRUSES OCCURRED AT ONLY SEVEN KEY POSITIONS ON THE PERIPHERY OF THE HA RECEPTOR BINDING SITE (RBS), AND THAT SEVEN OUT OF TEN A/H3N2 CLUSTER TRANSITIONS WERE CAUSED BY JUST SINGLE AMINO ACID SUBSTITUTIONS. FURTHERMORE, MAJOR ANTIGENIC CHANGE IN OTHER (SUB)TYPES OF HUMAN INFLUENZA, AS WELL AS INFLUENZA VIRUSES IN OTHER SPECIES, IS ALSO PRIMARILY DUE TO SINGLE AMINO ACID SUBSTITUTIONS AT THE SAME SEVEN KEY HA SITES, AND NEARBY, ON THE PERIPHERY OF THE HA RBS. THIS DISCOVERY RAISES AN IMMEDIATE, AND NOT PREVIOUSLY OBVIOUS QUESTION: IF JUST ONE AMINO ACID CHANGE IS TYPICALLY REQUIRED TO ESCAPE IMMUNITY, WHY IS THE ANTIGENIC EVOLUTION OF INFLUENZA VIRUSES SO SLOW? HUMAN SEASONAL INFLUENZA A/H3N2 VIRUSES REMAIN IN AN ANTIGENIC CLUSTER FOR AN AVERAGE OF 3.1 YEARS, AND OCCASIONALLY AS LONG AS EIGHT YEARS. THIS IS ESPECIALLY PERPLEXING GIVEN THAT, AS AN RNA VIRUS, INFLUENZA VIRUSES HAVE A FAST RATE OF MOLECULAR EVOLUTION. A POSSIBLE EXPLANATION FOR THE DELAY IN FIXATION OF CLUSTER TRANSITION SUBSTITUTIONS IS THAT ANTIGENIC CHANGE INCURS A FITNESS COST. THE PROXIMITY OF ESCAPE MUTATIONS TO THE RBS OFFERS A MECHANISM FOR THIS COST: THE VIRUS NEEDS TO CHANGE CLOSE TO THE RBS AS ANTIBODIES TARGETING THE RBS NEED TO BE ESCAPED, BUT CHANGE IN THIS AREA ALSO AFFECTS RECEPTOR-BINDING FUNCTION. SUBSTITUTIONS WHICH ADVANCE A STRAIN ANTIGENICALLY MAY ONLY BE COMPETITIVE WHEN SUFFICIENT POPULATION IMMUNITY HAS BUILT TO CONTEMPORARY CIRCULATING VARIANTS, SUCH THAT THE GAIN IN FITNESS FROM ESCAPING IMMUNITY (THE “EXTRINSIC” FITNESS GAIN) OUTWEIGHS THE POTENTIAL FITNESS LOSS ASSOCIATED WITH THE CONCOMITANT DISTORTION OF THE RECEPTOR BINDING SITE (THE “INTRINSIC” FITNESS LOSS). WE REFER TO THIS AS THE “FITNESS EXCHANGE” HYPOTHESIS. TO UNDERSTAND THE EVOLUTIONARY DYNAMICS OF INFLUENZA REQUIRES UNDERSTANDING WHAT PACES ANTIGENIC CHANGE. IN THIS PROPOSAL WE SET OUT TO TEST THE FITNESS EXCHANGE HYPOTHESIS, TO GAIN UNDERSTANDING OF THE VARIATION AND IMPACT OF VIRAL INTRINSIC FITNESS, AND TO DETERMINE THE RELATIVE IMPORTANCE OF INTRINSIC FITNESS AND STOCHASTIC EFFECTS IN NOVEL MUTATIONS BECOMING FIXED IN VIRAL POPULATIONS, AND TO INTEGRATE EMPIRICAL MEASUREMENTS OF THESE EFFECTS INTO A PROBABILISTIC FRAMEWORK FOR PREDICTING THE ANTIGENIC EVOLUTION OF SEASONAL INFLUENZA VIRUSES.

WASTE DISPOSAL GRANTS - REGULAR

CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND- IHES (CFDA: 84:425E)

B-RAF DRIVES REGENERATIVE AXON GROWTH IN THE OPTIC NERVE IN VIVO

RETINAL NEURAL PROCESSING DURING RETINAL DEGENERATIVE DISEASES

DATA COORDINATING CENTRE FOR ATTRACT TRIAL

OPTICAL DISSECTION OF INTRACORTICAL CIRCUITS SUPPORTING MOTOR RECOVERY AFTER SPINAL CORD INJURY

TRANSCRIPTIONAL REGULATION OVER NEUROGENESIS OF CORTICAL OUTPUT NEURON SEGMENTAL IDENTITY AND DIVERSITY - SUBCEREBRAL PROJECTION NEURONS (SCPN) RESIDE IN THE NEOCORTEX, AND EXTEND AXONS TO SUBCEREBRAL TARGETS IN THE BRAINSTEM AND SPINAL CORD. CORTICOSPINAL NEURONS (CSN), A SUBCLASS OF SCPN, PROJECT TO THE SPINAL CORD AND THEIR AXONS FORM THE CORTICOSPINAL TRACT (CST), A CRITICAL CIRCUIT FOR VOLUNTARY MOTOR CONTROL. IN ADDITION, PROJECTIONS FROM THE NEOCORTEX TO BRAINSTEM TARGETS FUNCTION IN PARALLEL WITH CSN TO EXERT MOTOR CONTROL. DEGENERATION OF THESE PROJECTION NEURONS IN AMYOTROPHIC LATERAL SCLEROSIS (ALS), ALONG WITH DEGENERATION OF SPINAL MOTOR NEURONS, CAUSES SPASTICITY AND PARALYSIS. IN HUMANS, DAMAGE TO THE CST AFTER SPINAL CORD INJURY IS A PRINCIPAL CAUSE OF LOSS OF VOLUNTARY MOTOR CONTROL. FURTHER, INTEGRITY OF CORTICOSPINAL CONNECTIVITY IS CENTRALLY LINKED TO RECOVERY FROM STROKE AND CEREBRAL PALSY. THERE HAVE BEEN MULTIPLE INVESTIGATIONS DETAILING THE ROLE OF CORTICO-BRAINSTEM VS. CORTICOSPINAL PROJECTIONS IN BOTH MOTOR CONTROL, AS WELL AS THEIR DISTINCT CONTRIBUTIONS TO FUNCTIONAL RECOVERY IN THESE DISTINCT CAUSES OF PARALYSIS. HOWEVER, IT REMAINS UNCLEAR WHEN AND HOW THESE DISTINCT PROJECTIONS ARE ESTABLISHED DURING DEVELOPMENT. UNDERSTANDING THE MOLECULAR BASIS OF THIS SPECIFICATION AND DIFFERENTIATION DURING DEVELOPMENT THEREFORE HOLDS SIGNIFICANT PROMISE IN ESTABLISHING APPROACHES THAT ARE TAILORED TO ENHANCING PLASTICITY OF THESE RELATED, YET DISTINCT CIRCUITS. A NECESSARY FIRST STEP TOWARD THIS ULTIMATE GOAL IS TO IDENTIFY THE MOLECULAR MECHANISMS DIRECTING SCPN AXONS TO BRAINSTEM (CORTICO-BRAINSTEM NEURONS) VERSUS SPINAL CORD (CSN). ONGOING WORK IN OUR LAB HAS IDENTIFIED THAT SUCH PROJECTIONS ARE INITIALLY SPECIFIED DURING THE PROCESS OF AXON EXTENSION DURING DEVELOPMENT. WE HAVE IDENTIFIED THAT CORTICO-BRAINSTEM AND CORTICOSPINAL NEURONS EXPRESS DISTINCT GENES AND CAN BE MOLECULARLY DISTINGUISHED IN MICE BY BIRTH. FURTHER OUR DATA SUGGEST THAT THE TRANSCRIPTIONAL REGULATOR SATB2 ACTS, IN PART, TO SPECIFY CORTICO-BRAINSTEM NEURONS. THIS PROPOSAL INVESTIGATES THE HYPOTHESIS THAT TRANSCRIPTIONAL REGULATION CONTROLS THE DEVELOPMENT OF CORTICO-BRAINSTEM VS. CORTICOSPINAL PROJECTIONS BY LATE EMBRYONIC DEVELOPMENT IN MICE. BUILDING ON THIS FOUNDATION, WE WILL FIRST IDENTIFY THE TIME POINT IN DEVELOPMENT WHEN THESE PROJECTIONS ARE SPECIFIED USING KNOCK-IN CRE REPORTER MICE (AIM 1). THIS WILL BE TESTED USING INTRACEREBRAL INJECTIONS OF AAV-REPORTERS AT DISTINCT DEVELOPMENTAL TIMES IN UTERO WITH ADULT ANALYSIS OF AXONAL PROJECTIONS. IN AIM 2, WE WILL INVESTIGATE THE TRANSCRIPTIONAL TARGETS OF SATB2 IN SCPN AT LATER DEVELOPMENTAL TIMES BY PROFILING ALL SCPN IN SATB2 WT AND CONDITIONAL KO MICE, AS WELL AS BY SATB2 OVEREXPRESSION, AT SINGLE CELL RESOLUTION. FINALLY, IN AIM 3 USING SUBPOPULATION-SPECIFIC TRANSGENIC CRE LINES, WE WILL INVESTIGATE SCPN AXON TARGETING IN BOTH SATB2 LOSS- AND GAIN-OF-FUNCTION. IN ADDITION, WE WILL INVESTIGATE WHETHER MISEXPRESSION OF SATB2 TARGET GENES CAN ALTER SCPN TARGETING TO THE BRAINSTEM VS. SPINAL TARGETS. TOGETHER, OUR WORK WILL DISCERN IN-DEPTH, THE MECHANISMS OF WHEN AND HOW TRANSCRIPTIONAL REGULATION CONTROLS SCPN SEGMENTAL “IDENTITY” THEREBY PROVIDING A MECHANISTIC FRAMEWORK FOR SUBSEQUENT IDENTIFICATION OF MOLECULES CONTROLLING SEGMENTALLY APPROPRIATE SCPN CONNECTIVITY WITH SUBCEREBRAL TARGETS.

PUBLIC HOUSING CAPITAL FUND

ROLE OF CD36 IN FUNCTIONAL RECOVERY IN CHRONIC STROKE

THE ROLE OF NEURONAL HYPEREXCITABILITY AND PROTEOSTASIS IN ALZHEIMER'S DISEASE - KEY PRODROMAL EVENTS IN ALZHEIMER’S DISEASE (AD) REVOLVE ON ALTERED ELECTRICAL SIGNALS AND BUILDUP OF GARBAGE PROTEINS IN VULNERABLE AREAS BEFORE SIGNS OF AD (LOCUS COERULEUS, LC)) AND AS DISEASE PROGRESSES TO BRAIN REGIONS THAT GOVERN MEMORY (HIPPOCAMPUS, HPC) AS DISEASE SEVERITY INCREASES. THIS STUDY BRIDGES THE POTENTIAL LIFESPAN OF DISEASE PROGRESSION USING A MOUSE MODEL OF AD PATHOLOGY TO EXAMINE HOW MODIFICATIONS IN BRAIN ACTIVITY CAN LEAD TO DISEASE. THE LC, WHILE NOT TRADITIONALLY ASSOCIATED WITH AD, IS THE SITE OF SOME OF THE EARLIEST PATHOLOGY IN AD, AS EARLY AS PEOPLE IN THEIR 20S. IT IS ALSO AN AREA REGULATING FLIGHT OR FIGHT RESPONSE AND AROUSAL. IN AD, THE HYPEREXCITATION OR UNREGULATED AROUSAL (HYPERAROUSAL) MAY BE A KEY EVENT IN MOVING THE DISEASE FROM AREAS LIKE THE LC, OR ANOTHER AREA WITH EARLY PATHOLOGY, THE ENTORHINAL CORTEX (EC) TO THE HIPPOCAMPUS OR OTHER CORTICAL REGIONS THAT ARE MORE COMMONLY ASSOCIATED WITH ALZHEIMER’S. IN AD, THE ACCUMULATION OF AGGREGATED PROTEINS DUE TO ALTERED CELLULAR PROCESSES, SPECIFICALLY, THE REGULATION OF PROTEIN LIFE CYCLE (PROTEOSTASIS) AND DYSFUNCTION OF AUTOPHAGIC-LYSOSOMAL AND UBIQUITIN-PROTEASOMAL SYSTEMS IS A KEY FEATURE OF NEUROPATHOLOGY. THESE PROCESSES ARE RESPONSIBLE FOR CLEARING THE GARBAGE IN CELLS AND DECLINES WITH AGE AND IS ACCELERATED IN DISEASE. WHILE WE KNOW LOSS OF PROTEOSTASIS CAN IMPAIR CELLULAR FUNCTION, HOW IT CAN IMPEDE NEURONAL ACTIVITY HAS NOT BEEN WELL ADVANCED. IN THIS APPLICATION, WE PROPOSE THAT A PRIMARY EVENT EARLY ON IS THE ALTERATION OF NEURAL NETWORKS IN THE LC (AND EC), LEADS TO THE PATHOLOGICAL HALLMARKS OF AD INCLUDING HIPPOCAMPAL PATHOLOGY. DEMONSTRATING HYPERACTIVATION AND PROTEOSTASIS DEFICITS IN THE LC AS INSTIGATORS OF HIPPOCAMPAL PATHOLOGY, PARTICULARLY, SELECTIVE NEURONAL LOSS PROVIDES MECHANISTIC INSIGHT AS TO WHY THESE ARE KEY NEURAL NETWORK CHANGES IN DISEASE. TO MODEL ALZHEIMER’S PATHOLOGY, WE FOCUS ON THE LC AND HPC TO IDENTIFY HOW THESE REGIONS ARE DISRUPTED WHEN PROTEOSTASIS SLOWS DOWN AND HOW HYPEREXCITATION IMPACTS THESE FUNCTIONS. WE WILL TRACK EARLY ELECTROPHYSIOLOGICAL CHANGES IN THE LC AND HPC WHEN PROTEINS LIKE BETA-AMYLOID (A) AND TAU START ACCUMULATING AND ASSESS HYPERAROUSAL/EXCITATION USING ELECTROPHYSIOLOGICAL MEASUREMENTS. OVER TIME, HYPEREXCITATION REDUCES CLEARANCE OF ABERRANT PROTEINS RESULTING IN A POSITIVE FEEDBACK LOOP OF PROTEOSTASIS LOSS AND HYPERAROUSAL, AND CASCADE TO HIPPOCAMPUS AND MEMORY LOSS. WE IDENTIFY THE TYPE OF NEURONS THAT ARE MOST VULNERABLE TO HYPEREXCITATION/AROUSAL-PROTEOSTASIS CHANGES IN THIS NETWORK, DESTABILIZING EXCITATORY-INHIBITORY HOMEOSTASIS. FINALLY, WE TEST IF DAMPENING HYPEREXCITATION OR PROTEOSTASIS RESTORATION IMPROVES COGNITIVE FUNCTION AND REVERSES PATHOLOGICAL CHANGES IN OUR MODEL. OUR GOAL IS TO USE OBSERVATIONS FROM ALL THE PARADIGMS TO IDENTIFY IF THESE BIOLOGICAL CHANGES AND PATHOLOGICAL SPREAD OF DISEASE CAN BE ANALYZED USING COMPUTATIONAL TOOLS TO PREDICT THE PATTERNS AND EVENTS LEADING TO AD AND TO TEST IF WE CAN USE AS A DISEASE RISK SCORE.

2/2 CATHETER-DIRECTED THERAPY FOR CHRONIC DVT (C-TRACT TRIAL)-DCC

USING TRANSCRIPTION FACTORS TO ENHANCE TRANSPLANTED CELL SURVIVAL FOR SCI REPAIR

TARGETING STROKE-INDUCED BRAIN SWELLING IN OBESE SUBJECTS: ROLE OF VEGF

USING MULTI-MODAL DATA INTEGRATION ACROSS BREAST CANCER MOLECULAR SUBTYPES TO DEVELOP PREDICTORS OF TREATMENT RESPONSE, EARLY RELAPSE, AND SURVIVAL AND TO EXPLORE EARLY SIGNALS OF LATER METASTATIC RECURRENCE

IMPACT OF SENSORY IMPAIRMENTS ON MOVEMENT IN CHILDREN WITH CEREBRAL PALSY

IMPACT OF BDNF SNP ON STROKE-INDUCED PLASTICITY AND MOTOR FUNCTION

ALLELIC CHOICE IN RETT SYNDROME

HDAC6: A TARGET FOR REGENERATION FOLLOWING INJURY IN THE NERVOUS SYSTEM

A NOVEL COMBINATORIAL APPROACH TO RESTORE MOTOR FUNCTION AFTER SPINAL CORD INJURY

MOTOR CORTEX ELECTRICAL STIMULATION TO AUGMENT SPONTANEOUS RECOVERY AFTER CHRONIC SUBCORTICAL STROKE

BENFOTIAMINE IN ALZHEIMER'S DISEASE: A PILOT STUDY

ROLE OF MATRIX METALLOPROTEINASES IN SUBCAPSULAR CATARACT FORMATION

BRAIN AND BEHAVIOR IN INDIVIDUALS WITH INTERSEX CONDITIONS

24/7 CLOSED-LOOP IN OLDER SUBJECTS WITH TYPE 1 DIABETES

THE ROLE OF THE INTESTINAL MICROBIOME IN ANXIETY AND DEPRESSION

MOLECULAR REGULATION OVER THE DECLINE IN LONG-DISTANCE CORTICOSPINAL AXON REGENERATIVE ABILITY DURING DEVELOPMENT - CORTICOSPINAL NEURONS (CSN) RESIDE IN THE NEOCORTEX, AND EXTEND AXONS TO SPECIFIC SEGMENTAL TARGETS IN THE SPINAL CORD FORMING THE CORTICOSPINAL TRACT (CST). CSN CRITICALLY CONTROL VOLUNTARY MOVEMENT AND ARE CENTRALLY INVOLVED IN RECOVERY FROM PARALYSIS ORIGINATING FROM MULTIPLE CAUSES, E.G., STROKE, SPINAL CORD INJURY (SCI), CEREBRAL PALSY, ETC.. CSN DEGENERATION IN AMYOTROPHIC LATERAL SCLEROSIS (ALS), ALONG WITH DEGENERATION OF SPINAL MOTOR NEURONS, CAUSES SPASTICITY AND PARALYSIS. RECOVERY IN ALL THESE DISTINCT CAUSES OF PARALYSIS WOULD ULTIMATELY REQUIRE LONG-DISTANCE CST REGENERATION, WHICH REMAINS AN UNATTAINED GOAL IN REGENERATIVE NEUROSCIENCE. PREVIOUS WORK USING NEONATAL LESIONS HAS ESTABLISHED CST REGENERATIVE ABILITY DECLINES FROM DEVELOPMENT INTO ADULTHOOD. WHEN THE CST IS DAMAGED IN EARLY LIFE, THERE IS GREATER PLASTICITY AND REGENERATION AS COMPARED TO SIMILAR LESIONS IN THE ADULT. HOWEVER, DESPITE THIS WORK, WE STILL DO NOT KNOW WHEN LONG-DISTANCE REGENERATIVE ABILITY IS LOST DURING DEVELOPMENT. THIS IS BECAUSE A KEY LIMITATION OF THESE ESTABLISHED NEONATAL LESION MODELS IS THAT THEY MASSIVELY DISRUPT THE SPINAL ENVIRONMENT AND THEREBY INTERFERE WITH THE NORMAL PROCESS OF LONG- DISTANCE CSN AXON EXTENSION DURING DEVELOPMENT. THIS LIMITS THE ABILITY OF THESE LESION PARADIGMS TO ASSESS THE ABILITY OF THE CNS TO SUPPORT LONG-DISTANCE REGENERATION. WE RECENTLY ESTABLISHED A NOVEL MICROSURGICAL APPROACH TO AXOTOMIZE THE CST DURING DEVELOPMENT, WHILE LEAVING THE SPINAL ENVIRONMENT RELATIVELY INTACT. WE IDENTIFIED THAT LONG-DISTANCE CST REGENERATIVE ABILITY IS LOST AT DIFFERENT TIMES AT DISTINCT SPINAL LEVELS– AT POSTNATAL DAY 4 (P4) THE CST CAN FULLY REGENERATE WHEN LESIONED AT THORACIC T11, BUT FAILS TO DO SO WHEN LESIONED AT CERVICAL C2. OUR RESULTS INDICATE THAT THE LOSS OF LONG-DISTANCE CST REGENERATIVE ABILITY CLOSELY PARALLELS THE DEVELOPMENTAL TIMELINE OF NORMAL CST GROWTH INTO THE SPINAL CORD, WHICH SUGGESTS THAT THE NORMAL PROCESS OF DIFFERENTIATION, BOTH IN CSN AND IN THE SPINAL CORD, RESULTS IN THE LOSS OF LONG-DISTANCE REGENERATIVE ABILITY. THIS PROPOSAL INVESTIGATES THE HYPOTHESIS THAT INHIBITION OF DIFFERENTIATION TO PROLONG THE IMMATURE DEVELOPMENTAL STATE WILL EXTEND THE TIME WINDOW WHEN LONG-DISTANCE REGENERATION IS POSSIBLE. SPECIFICALLY, WE WILL MANIPULATE THE FUNCTION OF RE1 SILENCING TRANSCRIPTION FACTOR (REST), A GLOBAL REPRESSOR OF NEURAL DIFFERENTIATION, TO TEST THIS HYPOTHESIS. BUILDING ON THIS FOUNDATION, WE WILL FIRST MANIPULATE REST FUNCTION (BOTH GAIN- AND LOSS-OF FUNCTION) AT DISTINCT SPINAL LEVELS TO INVESTIGATE WHETHER THIS AFFECTS THE ABILITY OF THESE SPINAL SEGMENTS TO SUPPORT LONG-DISTANCE CST REGENERATION (AIM1). WE WILL MANIPULATE REST FUNCTION IN CSN TO SIMILARLY INVESTIGATE LONG-DISTANCE CST REGENERATION (AIM 2). FINALLY, WE WILL USE SINGLE CELL PROFILING TO INVESTIGATE POTENTIALLY DISTINCT MOLECULAR EFFECTS OF MICROLESIONS AT DISTINCT SPINAL LEVELS ON DISTINCT CSN SUBSETS DEPENDING ON THEIR DEVELOPMENTAL STATE (AIM 3). TOGETHER, OUR WORK WILL DISCERN NOVEL MOLECULAR MECHANISMS OF HOW LONG-DISTANCE CST REGENERATION IS REGULATED DURING DEVELOPMENT, THEREBY PROVIDING A MECHANISTIC FRAMEWORK FOR SUBSEQUENT IDENTIFICATION OF MOLECULES THAT CAN BE USED TO EFFECT LONG-DISTANCE CST REGENERATION IN THE ADULT CNS.

THE ROLE OF CORTICOSPINAL NEURONS IN THE RECOVERY OF DEXTEROUS FORELIMB FUNCTION AFTER SPINAL CORD INJURY - PROJECT SUMMARY: THE ADVERSE EFFECTS OF SPINAL CORD INJURY (SCI) ON CORTICOSPINAL FUNCTION ARE NOT RESTRICTED TO THE DAMAGED SPINAL CORD, BUT ALSO DISRUPT MOTOR REPRESENTATIONS WITHIN THE CORTEX. SCI RESULTS IN ALTERED CORTICAL MAPS THAT REPRESENT MOTOR OUTPUT, WITH REPRESENTATIONS ABOVE THE LEVEL OF INJURY EXPANDING INTO AFFECTED CORTICAL AREAS. REHABILITATION IS NECESSARY FOR BOTH THE RECOVERY OF CORTICOSPINAL-DEPENDENT FORELIMB FUNCTION AND THE COMMENSURATE REORGANIZATION OF DISRUPTED CORTICAL MOTOR MAPS. BOTH THE UNDERLYING CIRCUIT MECHANISMS THAT SUPPORT CORTICAL REORGANIZATION AFTER SCI AS WELL AS THE NECESSITY FOR THE REORGANIZED CIRCUITRY TO SUPPORT FUNCTIONAL RECOVERY, REMAIN UNKNOWN. FOR INJURED CORTICOSPINAL NEURONS TO CONTRIBUTE TO FUNCTIONAL RECOVERY, THEY MUST BE INTEGRATED INTO CORTICAL MOTOR NETWORKS. THE LONG-TERM GOAL IS TO DEVELOP THERAPEUTIC INTERVENTIONS FOR SUPPORTING FUNCTIONAL RECOVERY AFTER SCL THE OVERALL OBIECTIVE FOR THIS PROPOSAL IS TO DETERMINE HOW SPECIFIC REHABILITATION AFTER SCI PROMOTES REMODELING OF CORTICOSPINAL CIRCUITS AND THE CONTRIBUTION OF INJURED CORTICOSPINAL NEURONS TO MOTOR RECOVERY. THE CENTRAL HYPOTHESIS IS THAT CORTICOSPINAL-DEPENDENT REHABILITATION AFTER SCI DIRECTS THE STRUCTURAL REMODELING OF INJURED CORTICOSPINAL NEURONS RESULTING IN THEIR INCORPORATION INTO FUNCTIONAL MOTOR ENSEMBLES. THE RATIONALE FOR THE PROPOSED RESEARCH IS THAT DETERMINING THE PROPERTIES OF REHABILITATIVE TRAINING THAT PROMOTE SUCCESSFUL CORTICOSPINAL CIRCUIT INCORPORATION INTO CORTICAL MOTOR NETWORKS AFTER SCI WILL BE CRUCIAL FOR DEVELOPING EFFECTIVE REHABILITATIVE STRATEGIES. THE FOLLOWING THREE SPECIFIC AIMS ARE PROPOSED: 1) IDENTIFY THE NATURE OF STRUCTURAL AND CONNECTIVITY CHANGES THAT OCCUR IN INJURED CORTICOSPINAL NEURONS DURING REHABILITATION-MEDIATED RECOVERY FROM SCI; 2) IDENTIFY THE CHANGES IN THE FUNCTIONAL CONNECTIVITY OF INJURED CORTICOSPINAL NEURONS DURING REHABILITATION-MEDIATED RECOVERY FROM SCI; AND 3) IDENTIFY THE CONTRIBUTION OF INJURED CORTICOSPINAL NEURONS TO MOTOR RECOVERY AFTER SCL FOR THE FIRST AIM, THE APPROACH WILL BE TO IMAGE STRUCTURAL CHANGES OF INJURED CORTICOSPINAL DENDRITIC ARBORS IN RESPONSE TO REHABILITATION. IN THE SECOND AIM, THE APPROACHES WILL BE TO USE 2-PHOTON IMAGING TO RECORD THE ACTIVITY OF INJURED CORTICOSPINAL NEURONS DURING REHABILITATION AND TO USE RETROGRADE TRANSSYNAPTIC TRACING TO IDENTIFY PRESYNAPTIC INPUTS. IN THE THIRD AIM, THE APPROACH WILL BE TO OPTOGENETICALLY CONTROL INJURED CORTICOSPINAL NEURONS IN AWAKE, BEHAVING MICE TO DETERMINE THEIR CONTRIBUTION TO RECOVERY. THE PROPOSED STUDIES ARE INNOVATIVE IN THAT THEY SHIFT THE FOCUS OF SPINAL CORD REHABILITATION ONTO THE CIRCUIT MECHANISMS OF CORTICAL NETWORK PLASTICITY. THE PROPOSED STUDIES ARE SIGNIFICANT BECAUSE THEY WILL ELUCIDATE THE MECHANISMS BY WHICH CIRCUIT REMODELING INFLUENCES RECOVERY AND WILL INFORM COMBINATORIAL STRATEGIES THAT TARGET CORTICAL PLASTICITY TO FULLY REALIZE THE EFFECTS OF AXONAL SPROUTING AND REGENERATION. THE EXPECTATION IS THAT COMPLETION OF THE PROPOSED RESEARCH WILL DETERMINE THE ROLE FOR INJURED CORTICOSPINAL NEURONS IN THE RECOVERY OF FUNCTIONAL MOTOR NETWORKS AFTER SCI_ THESE FINDINGS WILL ESTABLISH A FOUNDATION TO GUIDE THE DEVELOPMENT OF THERAPEUTIC STRATEGIES TARGETING MOVEMENT RECOVERY AFTER CNS INJURY.

HYPOXIA RESPONSE IN THE STROMA DURING TUMORIGENESIS

PURCHASE OF MOBILE CRANES 182-TON CAPACITY CRAWLER, 55-TON MOBILE CRANE, 30-TON ROUGH TERRAIN CRANE

MECHANISMS OF VASCULAR MIMICRY IMPACTING TUMOR PROGRESSION AND RESPONSE TO THERAPY IN BREAST CANCER

LARGE-SCALE SYSTEMATIC PRIORITIZATION OF PLASMODIUM VIVAX BLOOD STAGE VACCINE ANTIGENS

SIGNETS SIGNAL AND INFORMATION GATHERING FOR NETWORKED SURVEILLANCE

MYELOID VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION & ITS ROLE IN TUMORIGENESIS

NIH DIRECTOR'S PIONEER AWARD: ANTIGENIC CARTOGRAPHY

PUBLIC HOUSING CAPITAL FUND

A RANDOMIZED TRIAL OF INFLUENZA VACCINATION OF HUTTERITE CHILDREN

THE STRUCTURAL BASIS OF NUCLEIC ACID RECOGNITION BY TOLL-LIKE RECEPTORS

PUBLIC HOUSING CAPITAL FUND

ECOLOGY AND EVOLUTION OF AVIAN INFLUENZA

PURPOSE: THE PUBLIC HOUSING CAPITAL FUND PROGRAM (CFP) WAS CREATED BY AN AMENDMENT TO THE 1937 ACT BY THE QUALITY HOUSING AND WORK RESPONSIBILITY ACT (QHWRA) IN 1998 (ADDING SECTION 9(D) TO THE 1937 ACT MERGING PREVIOUS MODERNIZATION AND DEVELOPMENT PROGRAMS). THE CFP PROVIDES FINANCIAL ASSISTANCE IN THE FORM OF GRANTS TO APPROXIMATELY 2,770 PUBLIC HOUSING AGENCIES (PHAS), SERVING NEARLY ONE MILLION UNITS, IN ALL 50 STATES AND TERRITORIES, TO CARRY OUT CAPITAL AND MANAGEMENT ACTIVITIES INCLUDING THOSE LISTED IN SECTION 9(D)(1) OF THE UNITED STATES HOUSING ACT OF 1937 (1937 ACT). THE MAIN PURPOSE OF THE CFP FORMULA GRANT IS TO FUND PUBLIC HOUSING MODERNIZATION, DEVELOPMENT, MANAGEMENT IMPROVEMENTS, AND THE OTHER ELIGIBLE ACTIVITIES DESCRIBED IN 24 CFR PART 905. ADDITIONAL INFORMATION ON THE PUBLIC HOUSING CAPITAL FUND IS LOCATED ON THE OFFICE OF CAPITAL IMPROVEMENTS WEBSITE: OFFICE OF CAPITAL IMPROVEMENTS | HUD.GOV / U.S. DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HUD) ADDITIONAL INFORMATION ON PUBLIC HOUSING FUNDING CAN BE FOUND BY ACCESSING THE WEBSITE BELOW AND REVIEWING THE PUBLIC HOUSING DASHBOARD LINKED UNDER THE “DATA DASHBOARD AND ANALYTICS”. PUBLIC HOUSING | HUD.GOV / U.S. DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HUD); ACTIVITIES TO BE PERFORMED: THE PHAS RECEIVE FEDERAL FUNDS FROM THE U.S. DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HUD) TO ADMINISTER THE PUBLIC HOUSING FUND. PUBLIC HOUSING CAPITAL FUNDS MAY ONLY BE USED FOR ACTIVITIES THAT ARE DESCRIBED AS ELIGIBLE ACTIVITIES IN 24 CFR 905.200 AND ARE EITHER SPECIFIED IN AN APPROVED 5-YEAR ACTION PLAN OR APPROVED BY HUD FOR EMERGENCY WORK OR WORK NEEDED BECAUSE OF A NON-PRESIDENTIALLY DECLARED NATURAL DISASTER. PUBLIC HOUSING DEVELOPMENT, MODERNIZATION, AND FINANCING ARE THE MAJOR ACTIVITIES TO BE PERFORMED. DEVELOPMENT IS ACTIVITIES AND RELATED COSTS THAT ADD TO (OR SIGNIFICANTLY RECONFIGURE) PUBLIC HOUSING UNITS IN A PHA’S INVENTORY, INCLUDING CONSTRUCTION AND ACQUISITION OF ADDITIONAL PUBLIC HOUSING UNITS, WITH OR WITHOUT REHABILITATION, AND ANY-AND-ALL UNDERTAKINGS NECESSARY FOR PLANNING, DESIGN, FINANCING, LAND ACQUISITION, DEMOLITION, CONSTRUCTION, OR EQUIPMENT OF PUBLIC HOUSING UNITS, AND RELATED BUILDINGS, FACILITIES, AND/OR APPURTENANCES (I.E., NON-DWELLING FACILITIES/SPACES). DEVELOPMENT ALSO INCLUDES ANY MIXED-FINANCE MODERNIZATION, ALL RELEVANT MODERNIZATION USES (OTHER THAN MANAGEMENT IMPROVEMENTS), FINANCING USES, AND DEVELOPMENT OF NON-DWELLING SPACE WHERE SUCH SPACE IS NEEDED TO ADMINISTER, AND IS OF DIRECT BENEFIT TO A PUBLIC HOUSING PROJECT (I.E. HOUSING DEVELOPED, ACQUIRED, OR ASSISTED BY A PHA UNDER THE 1937 ACT, AND THE IMPROVEMENT OF ANY SUCH HOUSING), INCLUDING THE RESIDENTS. FINANCING DEBT AND FINANCING COSTS (E.G., ORIGINATION FEES, INTEREST) INCURRED BY A PHA FOR DEVELOPMENT OR MODERNIZATION OF PUBLIC HOUSING PROJECTS, INCLUDING MIXED-FINANCE DEVELOPMENT, THE CAPITAL FUND FINANCING PROGRAM (CFFP), AND ANY OTHER USE AUTHORIZED UNDER SECTION 30 OF THE 1937 ACT. MODERNIZATION INCLUDES ALL ELIGIBLE ACTIVITIES EXCEPT FOR DEVELOPMENT AND FINANCING. PHYSICAL WORK IS A MAJOR ACTIVITY AND IS WORK THAT IS DONE ON THE PHYSICAL STRUCTURES, SITE, AND GROUNDS OF A PUBLIC HOUSING PROPERTY OR STRUCTURE. MAJOR PHYSICAL ACTIVITIES INCLUDE DEMOLITION, RECONFIGURATION, EMERGENCY ACTIVITIES, ENERGY EFFICIENCY, NON-ROUTINE MAINTENANCE, PLANNED CODE COMPLIANCE, AND VACANCY REDUCTION. THE MEASURABLE OUTCOME OF THIS GRANT IS THAT HUD WILL BE ABLE TO TRACK THE AMOUNT OF DOLLARS SPENT ON IMPROVEMENTS TO THE STRUCTURES, UNITS, COMMON AREAS, UTILITIES, AND OTHER ELIGIBLE ACTIVITIES. ; EXPECTED OUTCOMES: THE EXPECTED OUTCOMES FOR PUBLIC HOUSING CAPITAL FUNDS OF APPROXIMATELY $3.2 BILLION WILL BE PUT INTO THE DEVELOPMENT, MODERNIZATION, AND FINANCING OF NEARLY 1 MILLION PUBLIC HOUSING UNITS ACROSS ALL 50 STATES AND TERRITORIES. THE PUBLIC HOUSING UNITS ARE UPDATED TO BE DECENT, SAFE, SANITARY AND TO COMPLY WITH FEDERAL HOUSING STANDARDS. PHAS CAN ALSO USE A PORTION OF THE CAPITAL FUNDING FOR MANAGEMENT IMPROVEMENTS OR OPERATING ACTIVITIES INCLUDING SAFETY AND SECURITY COSTS.; INTENDED BENEFICIARIES: THE INTENDED BENEFICIARIES FOR PUBLIC HOUSING CAPITAL FUNDS ARE THE LOW-INCOME PUBLIC HOUSING RESIDENTS.; SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS.

PORT SECURITY GRANT PROGRAM

PUBLIC HOUSING CAPITAL FUND

PURPOSE: THE PUBLIC HOUSING CAPITAL FUND PROGRAM (CFP) WAS CREATED BY AN AMENDMENT TO THE 1937 ACT BY THE QUALITY HOUSING AND WORK RESPONSIBILITY ACT (QHWRA) IN 1998 (ADDING SECTION 9(D) TO THE 1937 ACT MERGING PREVIOUS MODERNIZATION AND DEVELOPMENT PROGRAMS). THE CFP PROVIDES FINANCIAL ASSISTANCE IN THE FORM OF GRANTS TO APPROXIMATELY 2,770 PUBLIC HOUSING AGENCIES (PHAS), SERVING NEARLY ONE MILLION UNITS, IN ALL 50 STATES AND TERRITORIES, TO CARRY OUT CAPITAL AND MANAGEMENT ACTIVITIES INCLUDING THOSE LISTED IN SECTION 9(D)(1) OF THE UNITED STATES HOUSING ACT OF 1937 (1937 ACT). THE MAIN PURPOSE OF THE CFP FORMULA GRANT IS TO FUND PUBLIC HOUSING MODERNIZATION, DEVELOPMENT, MANAGEMENT IMPROVEMENTS, AND THE OTHER ELIGIBLE ACTIVITIES DESCRIBED IN 24 CFR PART 905. ADDITIONAL INFORMATION ON THE PUBLIC HOUSING CAPITAL FUND IS LOCATED ON THE OFFICE OF CAPITAL IMPROVEMENTS WEBSITE: OFFICE OF CAPITAL IMPROVEMENTS | HUD.GOV / U.S. DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HUD) ADDITIONAL INFORMATION ON PUBLIC HOUSING FUNDING CAN BE FOUND BY ACCESSING THE WEBSITE BELOW AND REVIEWING THE PUBLIC HOUSING DASHBOARD LINKED UNDER THE “DATA DASHBOARD AND ANALYTICS”. PUBLIC HOUSING | HUD.GOV / U.S. DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HUD); ACTIVITIES TO BE PERFORMED: THE PHAS RECEIVE FEDERAL FUNDS FROM THE U.S. DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HUD) TO ADMINISTER THE PUBLIC HOUSING FUND. PUBLIC HOUSING CAPITAL FUNDS MAY ONLY BE USED FOR ACTIVITIES THAT ARE DESCRIBED AS ELIGIBLE ACTIVITIES IN 24 CFR 905.200 AND ARE EITHER SPECIFIED IN AN APPROVED 5-YEAR ACTION PLAN OR APPROVED BY HUD FOR EMERGENCY WORK OR WORK NEEDED BECAUSE OF A NON-PRESIDENTIALLY DECLARED NATURAL DISASTER. PUBLIC HOUSING DEVELOPMENT, MODERNIZATION, AND FINANCING ARE THE MAJOR ACTIVITIES TO BE PERFORMED. DEVELOPMENT IS ACTIVITIES AND RELATED COSTS THAT ADD TO (OR SIGNIFICANTLY RECONFIGURE) PUBLIC HOUSING UNITS IN A PHA’S INVENTORY, INCLUDING CONSTRUCTION AND ACQUISITION OF ADDITIONAL PUBLIC HOUSING UNITS, WITH OR WITHOUT REHABILITATION, AND ANY-AND-ALL UNDERTAKINGS NECESSARY FOR PLANNING, DESIGN, FINANCING, LAND ACQUISITION, DEMOLITION, CONSTRUCTION, OR EQUIPMENT OF PUBLIC HOUSING UNITS, AND RELATED BUILDINGS, FACILITIES, AND/OR APPURTENANCES (I.E., NON-DWELLING FACILITIES/SPACES). DEVELOPMENT ALSO INCLUDES ANY MIXED-FINANCE MODERNIZATION, ALL RELEVANT MODERNIZATION USES (OTHER THAN MANAGEMENT IMPROVEMENTS), FINANCING USES, AND DEVELOPMENT OF NON-DWELLING SPACE WHERE SUCH SPACE IS NEEDED TO ADMINISTER, AND IS OF DIRECT BENEFIT TO A PUBLIC HOUSING PROJECT (I.E. HOUSING DEVELOPED, ACQUIRED, OR ASSISTED BY A PHA UNDER THE 1937 ACT, AND THE IMPROVEMENT OF ANY SUCH HOUSING), INCLUDING THE RESIDENTS. FINANCING DEBT AND FINANCING COSTS (E.G., ORIGINATION FEES, INTEREST) INCURRED BY A PHA FOR DEVELOPMENT OR MODERNIZATION OF PUBLIC HOUSING PROJECTS, INCLUDING MIXED-FINANCE DEVELOPMENT, THE CAPITAL FUND FINANCING PROGRAM (CFFP), AND ANY OTHER USE AUTHORIZED UNDER SECTION 30 OF THE 1937 ACT. MODERNIZATION INCLUDES ALL ELIGIBLE ACTIVITIES EXCEPT FOR DEVELOPMENT AND FINANCING. PHYSICAL WORK IS A MAJOR ACTIVITY AND IS WORK THAT IS DONE ON THE PHYSICAL STRUCTURES, SITE, AND GROUNDS OF A PUBLIC HOUSING PROPERTY OR STRUCTURE. MAJOR PHYSICAL ACTIVITIES INCLUDE DEMOLITION, RECONFIGURATION, EMERGENCY ACTIVITIES, ENERGY EFFICIENCY, NON-ROUTINE MAINTENANCE, PLANNED CODE COMPLIANCE, AND VACANCY REDUCTION. THE MEASURABLE OUTCOME OF THIS GRANT IS THAT HUD WILL BE ABLE TO TRACK THE AMOUNT OF DOLLARS SPENT ON IMPROVEMENTS TO THE STRUCTURES, UNITS, COMMON AREAS, UTILITIES, AND OTHER ELIGIBLE ACTIVITIES. ; EXPECTED OUTCOMES: THE EXPECTED OUTCOMES FOR PUBLIC HOUSING CAPITAL FUNDS OF APPROXIMATELY $3.2 BILLION WILL BE PUT INTO THE DEVELOPMENT, MODERNIZATION, AND FINANCING OF NEARLY 1 MILLION PUBLIC HOUSING UNITS ACROSS ALL 50 STATES AND TERRITORIES. THE PUBLIC HOUSING UNITS ARE UPDATED TO BE DECENT, SAFE, SANITARY AND TO COMPLY WITH FEDERAL HOUSING STANDARDS. PHAS CAN ALSO USE A PORTION OF THE CAPITAL FUNDING FOR MANAGEMENT IMPROVEMENTS OR OPERATING ACTIVITIES INCLUDING SAFETY AND SECURITY COSTS.; INTENDED BENEFICIARIES: THE INTENDED BENEFICIARIES FOR PUBLIC HOUSING CAPITAL FUNDS ARE THE LOW-INCOME PUBLIC HOUSING RESIDENTS.; SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS.

PURPOSE: THE PUBLIC HOUSING CAPITAL FUND PROGRAM (CFP) WAS CREATED BY AN AMENDMENT TO THE 1937 ACT BY THE QUALITY HOUSING AND WORK RESPONSIBILITY ACT (QHWRA) IN 1998 (ADDING SECTION 9(D) TO THE 1937 ACT MERGING PREVIOUS MODERNIZATION AND DEVELOPMENT PROGRAMS). THE CFP PROVIDES FINANCIAL ASSISTANCE IN THE FORM OF GRANTS TO APPROXIMATELY 2,770 PUBLIC HOUSING AGENCIES (PHAS), SERVING NEARLY ONE MILLION UNITS, IN ALL 50 STATES AND TERRITORIES, TO CARRY OUT CAPITAL AND MANAGEMENT ACTIVITIES INCLUDING THOSE LISTED IN SECTION 9(D)(1) OF THE UNITED STATES HOUSING ACT OF 1937 (1937 ACT). THE MAIN PURPOSE OF THE CFP FORMULA GRANT IS TO FUND PUBLIC HOUSING MODERNIZATION, DEVELOPMENT, MANAGEMENT IMPROVEMENTS, AND THE OTHER ELIGIBLE ACTIVITIES DESCRIBED IN 24 CFR PART 905. ADDITIONAL INFORMATION ON THE PUBLIC HOUSING CAPITAL FUND IS LOCATED ON THE OFFICE OF CAPITAL IMPROVEMENTS WEBSITE: OFFICE OF CAPITAL IMPROVEMENTS | HUD.GOV / U.S. DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HUD) ADDITIONAL INFORMATION ON PUBLIC HOUSING FUNDING CAN BE FOUND BY ACCESSING THE WEBSITE BELOW AND REVIEWING THE PUBLIC HOUSING DASHBOARD LINKED UNDER THE “DATA DASHBOARD AND ANALYTICS”. PUBLIC HOUSING | HUD.GOV / U.S. DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HUD); ACTIVITIES TO BE PERFORMED: THE PHAS RECEIVE FEDERAL FUNDS FROM THE U.S. DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT (HUD) TO ADMINISTER THE PUBLIC HOUSING FUND. PUBLIC HOUSING CAPITAL FUNDS MAY ONLY BE USED FOR ACTIVITIES THAT ARE DESCRIBED AS ELIGIBLE ACTIVITIES IN 24 CFR 905.200 AND ARE EITHER SPECIFIED IN AN APPROVED 5-YEAR ACTION PLAN OR APPROVED BY HUD FOR EMERGENCY WORK OR WORK NEEDED BECAUSE OF A NON-PRESIDENTIALLY DECLARED NATURAL DISASTER. PUBLIC HOUSING DEVELOPMENT, MODERNIZATION, AND FINANCING ARE THE MAJOR ACTIVITIES TO BE PERFORMED. DEVELOPMENT IS ACTIVITIES AND RELATED COSTS THAT ADD TO (OR SIGNIFICANTLY RECONFIGURE) PUBLIC HOUSING UNITS IN A PHA’S INVENTORY, INCLUDING CONSTRUCTION AND ACQUISITION OF ADDITIONAL PUBLIC HOUSING UNITS, WITH OR WITHOUT REHABILITATION, AND ANY-AND-ALL UNDERTAKINGS NECESSARY FOR PLANNING, DESIGN, FINANCING, LAND ACQUISITION, DEMOLITION, CONSTRUCTION, OR EQUIPMENT OF PUBLIC HOUSING UNITS, AND RELATED BUILDINGS, FACILITIES, AND/OR APPURTENANCES (I.E., NON-DWELLING FACILITIES/SPACES). DEVELOPMENT ALSO INCLUDES ANY MIXED-FINANCE MODERNIZATION, ALL RELEVANT MODERNIZATION USES (OTHER THAN MANAGEMENT IMPROVEMENTS), FINANCING USES, AND DEVELOPMENT OF NON-DWELLING SPACE WHERE SUCH SPACE IS NEEDED TO ADMINISTER, AND IS OF DIRECT BENEFIT TO A PUBLIC HOUSING PROJECT (I.E. HOUSING DEVELOPED, ACQUIRED, OR ASSISTED BY A PHA UNDER THE 1937 ACT, AND THE IMPROVEMENT OF ANY SUCH HOUSING), INCLUDING THE RESIDENTS. FINANCING DEBT AND FINANCING COSTS (E.G., ORIGINATION FEES, INTEREST) INCURRED BY A PHA FOR DEVELOPMENT OR MODERNIZATION OF PUBLIC HOUSING PROJECTS, INCLUDING MIXED-FINANCE DEVELOPMENT, THE CAPITAL FUND FINANCING PROGRAM (CFFP), AND ANY OTHER USE AUTHORIZED UNDER SECTION 30 OF THE 1937 ACT. MODERNIZATION INCLUDES ALL ELIGIBLE ACTIVITIES EXCEPT FOR DEVELOPMENT AND FINANCING. PHYSICAL WORK IS A MAJOR ACTIVITY AND IS WORK THAT IS DONE ON THE PHYSICAL STRUCTURES, SITE, AND GROUNDS OF A PUBLIC HOUSING PROPERTY OR STRUCTURE. MAJOR PHYSICAL ACTIVITIES INCLUDE DEMOLITION, RECONFIGURATION, EMERGENCY ACTIVITIES, ENERGY EFFICIENCY, NON-ROUTINE MAINTENANCE, PLANNED CODE COMPLIANCE, AND VACANCY REDUCTION. THE MEASURABLE OUTCOME OF THIS GRANT IS THAT HUD WILL BE ABLE TO TRACK THE AMOUNT OF DOLLARS SPENT ON IMPROVEMENTS TO THE STRUCTURES, UNITS, COMMON AREAS, UTILITIES, AND OTHER ELIGIBLE ACTIVITIES. ; EXPECTED OUTCOMES: THE EXPECTED OUTCOMES FOR PUBLIC HOUSING CAPITAL FUNDS OF APPROXIMATELY $3.2 BILLION WILL BE PUT INTO THE DEVELOPMENT, MODERNIZATION, AND FINANCING OF NEARLY 1 MILLION PUBLIC HOUSING UNITS ACROSS ALL 50 STATES AND TERRITORIES. THE PUBLIC HOUSING UNITS ARE UPDATED TO BE DECENT, SAFE, SANITARY AND TO COMPLY WITH FEDERAL HOUSING STANDARDS. PHAS CAN ALSO USE A PORTION OF THE CAPITAL FUNDING FOR MANAGEMENT IMPROVEMENTS OR OPERATING ACTIVITIES INCLUDING SAFETY AND SECURITY COSTS.; INTENDED BENEFICIARIES: THE INTENDED BENEFICIARIES FOR PUBLIC HOUSING CAPITAL FUNDS ARE THE LOW-INCOME PUBLIC HOUSING RESIDENTS.; SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS.

THE ROLE OF ANDROGEN DEPRIVATION THERAPY IN DEPRESSION IN PATIENTS WITH PROSTATE CANCER: A LONGITUDINAL STUDY (RADICAL)

INJURY AND ADAPTATION IN THE DEVELOPING RAT CORTICOSPINAL AND RUBROSPINAL TRACTS

MICROBIOME BASED BIOMARKERS OF WOUND HEALING - ABSTRACT DIABETIC FOOT ULCERS (DFU) IMPACT OVER 2 MILLION AMERICANS ANNUALLY, RESULT IN OVER 130,000 AMPUTATIONS EACH YEAR, AND ARE ASSOCIATED WITH HIGH MORTALITY RATES. TO DATE, THERE HAS BEEN NO SINGLE INFECTIOUS AGENT OF DFU IDENTIFIED AS A GOOD MARKER OF HEALING OUTCOME. THIS IS LIKELY BECAUSE DFUS ARE HOST TO A DIVERSE COMMUNITY OF MICROBES (I.E., THE WOUND MICROBIOME). WOUND MICROBIOMES ANALYZED AT THE COMMUNITY-LEVEL ARE PROMISING PREDICTORS OF WOUND HEALING OUTCOMES. WE HAVE SHOWN THAT WOUNDS PERSISTING BEYOND 12 WEEKS EXHIBIT HIGH AND PERSISTENT PROPORTIONS OF MIXED-POPULATION, ANAEROBIC BACTERIA WITHIN THEIR MICROBIOMES. ADDITIONALLY, WE FOUND A SIGNIFICANT INCREASE OF ANAEROBIC TRANSCRIPTIONAL ACTIVITY IN PERSISTENT AND AMPUTATED WOUNDS, EVEN FROM SPECIES IDENTIFIED AS BEING IN LOW ABUNDANCE BY TRADITIONAL 16S RRNA BASED GENE SEQUENCING. THIS SUGGESTS MICROBIAL TRANSCRIPTION, AND SPECIFICALLY FROM ANAEROBIC BACTERIA, ARE PROMISING BIOMARKERS OF WOUND HEALING IN DIABETIC PATIENTS. THE PROPOSED PROJECT WILL IDENTIFY MICROBIAL BIOMARKERS THAT CAN BE USED AS PROGNOSTIC AND MONITORING TOOLS FOR DFU WOUND HEALING. WE HYPOTHESIZE USING RNA INSTEAD OF DNA WILL PROVIDE A BETTER SNAPSHOT OF THE WOUND ENVIRONMENT AND MORE SENSITIVE BIOMARKERS: SPECIFICALLY, THE PROPORTION AND TRANSCRIPTIONAL ACTIVITY OF ANAEROBES WITHIN THE WOUND MICROBIOME CAN BE USED AS PREDICTORS OF WOUND HEALING OUTCOMES. USING RNASEQ TO MEASURE THE METATRANSCRIPTOME OF THE DFU MICROBIOME, WE WILL LEVERAGE ADVANCES IN MACHINE LEARNING APPROACHES TO DEMONSTRATE THE CAPACITY OF THE ANAEROBIC COMPONENT OF THE WOUND MICROBIOME TO SERVE AS A BIOMARKER FOR WOUND HEALING. WE HAVE VIGOROUSLY EVALUATED THE OPTIMAL SAMPLE COLLECTION TECHNIQUES AND METHODS OF DETECTION, DETERMINING A SIMPLE SWAB OF THE ULCER BED IS SUFFICIENT TO CHARACTERIZE THE METATRANSCRIPTOME AND WILL FACILITATE CLINICAL IMPLEMENTATION. WE WILL DEVELOP A MULTIPLEXED RT-QPCR ASSAY FOR THE PANEL OF CANDIDATE BIOMARKER GENES WE IDENTIFY AND VALIDATE THE ASSAY SENSITIVITY, SPECIFICITY, ACCURACY AND PRECISION. WE WILL WORK CLOSELY WITH THE DIABETIC FOOT CONSORTIUM STEERING COMMITTEE AND DATA COORDINATING CENTER TO TEST AND VALIDATE OUR BIOMARKERS IN A MULTI-SITE TRIAL WITH THE DFC. OUR GOAL IS TO DEVELOP A MULTIPLEXED BIOMARKER ASSAY INTEGRATING THE COMPLEX INTERACTIONS OCCURRING WITHIN THE DFU MICROBIOME AND TISSUE MICROENVIRONMENT. IT WILL USE A SIMPLE SWAB OF THE ULCER BED, RELY ON OBJECTIVE MEASUREMENTS, AND IS DESIGNED TO PREDICT HEALING TRAJECTORIES AT AN EARLY TIME IN THE CLINICAL COURSE.

FAMILIES CREATED BY ASSISTED REPRODUCTION: PARENTING AND CHILD DEVELOPMENT

THIS GRANT IS A CONTINUATION OF N00014-14-1-0787 GUT MICROBES: POSITIVE EFFECTS ON NEGATIVE RESPONSES TO ENVIRONMENTAL STRESSORS

TAS::57 3600::TAS "NEURAL BASIS OF TARGET TRACKING IN INSECTS: IMPACT OF BODY SIZE AND FLIGHT STRATEGY"

DECODING HOW DISTINCT MECHANISMS OF GENOMIC INSTABILITY FOUND IN TNBC PATIENTS PROGRAM THE TISSUE MICROENVIRONMENT AND THERAPY RESPONSE AT METASTATIC SITES

UNDERSTANDING THE ROLE OF HYPOXIA IN VASCULOGENIC MIMICRY, RESPONSE TO THERAPY, AND METASTASIS

WASTE DISPOSAL GRANTS - REGULAR

PUBLIC HOUSING CAPITAL FUND

AN OPTOGENETIC TOOLKIT FOR THE INTERROGATION AND CONTROL OF SINGLE CELLS

PERFORM FUNDING SYS

EVALUATION AND COMPILATION OF NUCLEAR STRUCTURE AND DECAY DATA FOR THE US NUCLEAR DATA PROGRAM

USER-FRIENDLY OPEN-SOURCE PIPELINE FOR ANATOMICALLY PRECISE ANALYSIS OF SINGLE-TRIAL M/EEG - PROJECT SUMMARY MAGNETO- AND ELECTROENCEPHALOGRAPHY (M/EEG) MEASURE HUMAN BRAIN ACTIVITY NON-INVASIVELY, USING SENSORS PLACED ON OR ABOVE THE HEAD, WITH MILLISECOND ACCURACY, AND HAVE LONG BEEN USED TO STUDY NEURAL AND COGNITIVE PROCESSES. THIS PROJECT IS TO DEVELOP A USER-FRIENDLY, OPEN-SOURCE ANALYSIS PIPELINE TO MAKE RECENT INNOVATIONS IN ANALYSIS TECHNIQUES AVAILABLE TO A BROAD AUDIENCE. FIRST, M/EEG HAS TRADITIONALLY BEEN ANALYZED PRIMARILY AS EVENT-RELATED ACTIVITY (AN EXPERIMENT IS CONCEPTUALIZED AS A SERIES OF TRIALS, EACH CONSTITUTING A UNIQUE EVENT; FOR EXAMPLE, THE RESPONSE TO A SYLLABLE DA). SUCH EXPERIMENTS TYPICALLY REQUIRE MANY REPETITIONS OF IDENTICAL TRIALS TO SEPARATE SIGNAL FROM NOISE IN THE M/EEG RESPONSE. MORE RECENT TECHNIQUES ALLOW CONCEPTUALIZING EXPERIMENTAL TIME AS CONTINUOUS, WITH DIFFERENT ASPECTS OF STIMULI THAT ARE DISTRIBUTED IN TIME EVOKING DIFFERENT OVERLAPPING BRAIN RESPONSES (FOR EXAMPLE, THE AUDITORY CORTEX RESPONSE CONTINUOUSLY “TRACKS” THE ACOUSTIC ENVELOPE OF SPEECH, OR THE VISUAL CORTEX TRACKS THE AMOUNT OF VISUAL MOTION IN A MOVIE, ETC.). IN THIS TIME-CONTINUOUS ANALYSIS, NO REPEATED TRIALS ARE NECESSARY, AND THE SIGNAL IS INSTEAD ESTIMATED USING DETAILED MODELS OF THE STIMULI. SECOND, WHILE BRAIN ACTIVITY IS MEASURED OUTSIDE OF THE HEAD, IT HAS LONG BEEN POSSIBLE TO ESTIMATE ANATOMICALLY LOCALIZED SOURCES OF THIS ACTIVITY IN THE BRAIN, AND RECENT ADVANCES HAVE GREATLY IMPROVED THIS SOURCE ESTIMATION. THESE TWO ADVANCES (SINGLE-TRIAL CONTINUOUS ANALYSIS AND IMPROVED SOURCE LOCALIZATION) HAVE ONLY RECENTLY BEEN COMBINED SUCCESSFULLY, AND NO OFF-THE-SHELF SOFTWARE PACKAGE ALLOWS RESEARCHERS TO READILY APPLY THIS METHOD TO EXISTING OR NEW DATASETS. THIS PROJECT WILL DEVELOP SUCH A SOFTWARE TOOL WITH AN EASY-TO-USE PIPELINE FOR GROUP LEVEL ANALYSIS. THE TECHNIQUE THAT THIS TOOL WILL MAKE AVAILABLE IS ESSENTIAL FOR ANALYZING DATA FROM EXPERIMENTAL DESIGNS WITH NATURALISTIC STIMULI (FOR EXAMPLE, PARTICIPANTS WATCHING A MOVIE OR LISTENING TO AN AUDIOBOOK). SUCH EXPERIMENTS OFFER ENHANCED VALIDITY, AND ARE RICH AND VERSATILE: RESEARCHERS CAN TEST MANY DIFFERENT HYPOTHESES ABOUT WHAT NEURAL PROCESSES ARE EVOKED BY THE STIMULI. HOWEVER, THE TRADITIONAL AVERAGING TECHNIQUES THAT ARE WIDELY AVAILABLE ARE NOT REMOTELY SUITABLE. THE SOFTWARE TOOL DEVELOPED HERE IS IDEALLY SUITED FOR ANALYZING SUCH DATASETS. IT WILL BE MADE WIDELY ACCESSIBLE AND USER-FRIENDLY, TO LOWER THE THRESHOLD FOR NON-NEUROSCIENTISTS TO TEST HYPOTHESES ABOUT NEURAL REPRESENTATIONS. FOR EXAMPLE, EXISTING DATASETS OF AUDIOBOOK LISTENING COULD BE USED BY PSYCHOLOGISTS, COMPUTER SCIENTISTS AND LINGUISTS TO TEST HYPOTHESES ABOUT NEURAL REPRESENTATIONS OF SPEECH.

EARLY STAGE DEVELOPMENT OF A SELECTIVE KAPPA OPIOID RECEPTOR (KOR) ANTAGONIST TO TREAT ALCOHOL USE DISORDER

HOME TESTING OF 24/7 CLOSED-LOOP CONTROL IN CHILDREN AND ADOLESCENTS WITH TYPE 1

DESIGN OF TAILORED MATERIALS: FROM PRINCIPLE COMPONENT ALLOYS TO METAMATERIALS

TENSOR NETWORKS AND HOLOGRAPHIC SPACETIME

PUBLIC HOUSING CAPITAL FUND

AXONAL TRANSPORT AND LOCAL TRANSLATION IN NEUROPATHIC PAIN

MITAGS SAFETY & FIRE TRAINING FOR COMMERCIAL FISHING FLEET

WAVE-ICE INTERACTION AND THE MARGINAL ICE ZONE

NEW SPACES FOR DENOTATIONAL SEMANTICS

PERFORM FUNDING SYS

PUBLIC HOUSING CAPITAL FUND

CROSS-TALK BETWEEN SARMOPTOSIS AND FERROPTOSIS IN HEMORRHAGIC STROKE - PROJECT SUMMARY/ABSTRACT BRAIN BLEEDING IN THE PARENCHYMA, ALSO KNOWN AS INTRACEREBRAL HEMORRHAGE (ICH), REPRESENTS 10 TO 30 PERCENT OF STROKES IN DISTINCT COUNTRIES AROUND THE WORLD. DESPITE ITS LOWER INCIDENCE THAN ISCHEMIC STROKE, ICH CARRIES HIGHER RATES OF MORTALITY AND MORBIDITY. WORSE OUTCOMES IN HUMANS WITH ICH HAVE BEEN CORRELATED WITH DAMAGE TO AXONS IN AREAS OF THE BRAIN LIKE THE THALAMUS OR THE STRIATUM WHERE BLEEDING FROM SMALL, PENETRATING ARTERIES (OFTEN AFFECTED BY LONGSTANDING HYPERTENSION) TENDS TO OCCUR. RED BLOOD CELLS ACCUMULATE IN ICH AND LYSE AND RELEASE TOXINS. THESE INCLUDE HEMOGLOBIN (HGB) AND ITS BREAKDOWN PRODUCT HEMIN . ADDITIONAL UNDERSTANDING OF HOW HGB/HEMIN LEADS AXONS TO DEGENERATE IN ICH IS A STRATEGY TO FULLY ASSESS AND OVERCOME DISABILITY FROM THIS CONDITION. EXCITINGLY, A MOLECULAR PATH FOR PROGRAMMED AXONAL DESTRUCTION HAS BEEN DEFINED INVOLVING THE PROTEIN, STERILE ALPHA AND TOLL/INTERLEUKIN RECEPTOR-1 (TIR) MOTIF CONTAINING 1 (SARM1). SARM1'S DEGENERATIVE ACTIVITIES IN THE AXON EMERGE FROM ITS NADASE (NAD+ DEGRADING) ACTIVITY IN THE TIR DOMAIN. THIS DOMAIN'S IMPORTANCE IS HIGHLIGHTED BY ITS CONSERVATION FROM PLANTS TO HUMANS. IN PRELIMINARY STUDIES, WE FOUND THAT GERMLINE DELETION OF FULL LENGTH SARM1 PREVENTS AXONAL DAMAGE IN THE STRIATUM FOLLOWING ICH. SINCE PREVIOUS STUDIES FROM OUR LAB HAVE SHOWN THAT HEMIN INDUCES FERROPTOSIS, AN IRON-DEPENDENT, CASPASE-INDEPENDENT FORM OF PROGRAMMED NECROSIS, FOLLOWING EXPERIMENTAL ICH, WE ARE SEEKING TO UNDERSTAND THE CROSS TALK BETWEEN FERROPTOSIS AND SARM1-MEDIATED AXONAL DESTRUCTION (SARMOPTOSIS). OF NOTE, WE FOUND THAT CORTICAL NEURONS CULTURED FROM THE SARM1 KNOCKOUT MICE ARE PARTIALLY RESISTANT TO FERROPTOTIC STIMULI (HEMIN AND ERASTIN). MOREOVER, AGENTS SUCH AS P7C3 THAT AUGMENT THE CELL'S ABILITY TO MAKE NAD+ PROTECT AGAINST FERROPTOSIS; CONVERSELY, FK866, WHICH IMPEDES THE SAME NAD+ SYNTHESIZING PATHWAY MAKES FERROPTOSIS WORSE. FROM THESE PRELIMINARY STUDIES WE PROPOSE THREE AIMS DESIGNED TO UNDERSTAND THE INTERPLAY BETWEEN FERROPTOSIS AND SARMOPTOSIS IN ICH. IN THE FIRST AIM, WE WILL LEVERAGE MICE THAT POSSESS A GERMLINE, HOMOZYGOUS, SINGLE AMINO ACID MUTATION (E642A) IN THE NADASE DOMAIN OF SARM1. LIKE THE SARM1-/- MICE, THE NEURONS OF THESE MICE ARE RESISTANT TO AXOTOMY IN VITRO AND IN VIVO. THEY WILL BE USED TO PROBE WHETHER THE NADASE ACTIVITY IS CRITICAL FOR FERROPTOSIS IN VITRO AND ICH IN VIVO. IN THE SECOND AIM, WE WILL ADDRESS THE HYPOTHESIS THAT HEMIN-INDUCES AXONAL DEGENERATION VIA LOCAL FERROPTOTIC PATHWAYS THAT TRIGGER SARM1 ACTIVATION. WE WILL USE SENSORY NEURONS CULTURED IN CAMPENOT CHAMBERS TO ISOLATE CELL BODIES FROM AXONS AND QUERY THEIR POSSIBLY DISTINCT RESPONSES TO LETHAL CONCENTRATIONS OF HEMIN. WE WILL ALSO PROBE THE ROLE OF FERROPTOSIS AND SARMOPTOSIS IN THE DESTRUCTION OF CORTICOSPINAL TRACT AXONS IN VIVO. IN THE LAST AIM, WE WILL SEEK TO UNDERSTAND WHETHER INTERVENTIONS THAT TARGET FERROPTOSIS BY ACTING IN THE NUCLEUS (CELL BODY) CAN BE COMBINED WITH SARM1 DELETION (THAT ACTS PRIMARILY IN AXONS) IN MICE TO REDUCE DAMAGE AND IMPROVE BEHAVIORAL RECOVERY OVER EACH AGENT TESTED ALONE. AT THE CULMINATION OF THESE STUDIES, NEW MECHANISTIC INFORMATION WILL EMERGE REGARDING AXONAL AND CELL BODY LOSS FOLLOWING ICH WITH CLEAR THERAPEUTIC IMPLICATIONS.

GUT MICROBES: POSITIVE EFFECTS ON NEGATIVE RESPONSES TO ENVIRONMENTAL STRESSORS

PUBLIC HOUSING CAPITAL FUND

PUBLIC AND INDIAN HOUSING

NEURAL MECHANISMS UNDERLYING LINGUISTIC CONTEXT USE FOR SPEECH PROCESSING IN AGING - PROJECT SUMMARY/ABSTRACT A FREQUENT COMPLAINT IN OLDER ADULTS IS DIFFICULTY WITH SPEECH COMPREHENSION, ESPECIALLY IN THE PRESENCE OF BACKGROUND NOISE, SUCH AS WHEN AT A BUSY RESTAURANT. A COMMON STRATEGY THAT LISTENERS USE IN SUCH SITUATIONS IS TO USE THE LINGUISTIC CONTEXT TO FILL IN GAPS IN COMPREHENSION. OLDER ADULTS TEND TO DO WELL WITH THIS, AT LEAST IN LABORATORY SITUATIONS: GIVEN A MEANINGFUL LINGUISTIC CONTEXT, THEIR WORD RECOGNITION IS MUCH MORE LIKE YOUNG ADULTS’ THAN WHEN SPEECH IS MEANINGLESS. AN OPEN QUESTION IS WHAT COGNITIVE MECHANISMS UNDERLY THIS ABILITY. BASED ON RESEARCH IN YOUNG ADULTS, IT IS WIDELY BELIEVED THAT PREDICTION PLAYS A CENTRAL ROLE IN LANGUAGE PROCESSING – LISTENERS COULD PREDICT UPCOMING WORDS FROM A MEANINGFUL CONTEXT, AND THUS COMPENSATE FOR NOISY INPUT. YET, A LINE OF RESEARCH USING AN ELECTROENCEPHALOGRAPHY (EEG) SIGNATURE OF PREDICTIVE LANGUAGE PROCESSING, THE N400, SUGGESTS THAT PREDICTIVE PROCESSING IS IMPAIRED IN OLDER ADULTS. THIS RAISES THE QUESTION OF HOW, THEN, OLDER ADULTS CAN SUCCESSFULLY USE CONTEXT TO FACILITATE SPEECH RECOGNITION. THIS PROPOSAL USES CUTTING-EDGE NEUROIMAGING TECHNIQUES TO EXAMINE A WIDER RANGE OF PREDICTIVE SPEECH PROCESSING THAN PREVIOUS WORK, AS WELL AS NON- PREDICTIVE COMPENSATORY MECHANISMS, IN YOUNGER AND OLDER ADULTS. TO MAXIMIZE RELEVANCE TO OLDER ADULTS’ REAL- WORLD EXPERIENCE, BRAIN RESPONSES ARE MEASURED WHILE LISTENING TO CONTINUOUS NARRATIVE SPEECH, IN QUIET AND IN MULTI-TALKER BABBLE BACKGROUND NOISE, APPROXIMATING CONDITIONS IN A BUSY RESTAURANT. EEG IS USED TO MODEL THE TEMPORAL DYNAMICS OF PREDICTIVE LANGUAGE PROCESSING AT MULTIPLE LEVELS (ACOUSTIC-PHONETIC, SUBLEXICAL, LEXICAL, SENTENTIAL). THIS WILL TEST SEVERAL HYPOTHESIS THAT OLDER ADULTS USE PREDICTIONS DURING SPEECH PROCESSING, BUT AT DIFFERENT LEVELS THAN YOUNG ADULTS. FUNCTIONAL MAGNETIC RESONANCE IMAGING (FMRI) IS USED TO CHARACTERIZE LANGUAGE NETWORKS RELATED TO SPEECH PROCESSING IN QUIET AND IN NOISE. WHEREAS PREVIOUS RESEARCH HAS MOSTLY RELIED ON SMALL SAMPLE SIZES, OBSCURING INDIVIDUAL DIFFERENCES, THIS WORK WILL BE BASED ON A LARGE DATASET, ADEQUATELY POWERED FOR INDIVIDUAL DIFFERENCE ANALYSIS, AND WILL COLLECT A RANGE OF INDIVIDUAL VARIABLES THAT MAY BE RELATED TO SPEECH COMPREHENSION, SUCH AS HEARING ABILITY, WORKING MEMORY SPAN AND INHIBITORY FUNCTIONING. THIS WORK WILL RELATE INDIVIDUAL DIFFERENCES IN PREDICTION AT MULTIPLE LEVELS OF THE PROCESSING HIERARCHY TO LANGUAGE, COGNITIVE, AND FUNCTIONAL OUTCOMES. TOGETHER, THIS WORK AIMS TO UNCOVER WHICH COGNITIVE STRATEGIES (PREDICTIVE OR NON-PREDICTIVE), NEURAL REPRESENTATIONS AND NETWORK ARE RELATED TO SUCCESSFUL SPEECH COMPREHENSION IN OLDER ADULTS. BY RELATING NEURAL MEASURES TO COMPREHENSION, IT WILL DISTINGUISH BETWEEN SUCCESSFUL COMPENSATION AND MALADAPTIVE CHANGES IN BRAIN ACTIVATION. THE DATASET WILL BE SHARED PUBLICLY, PROVIDING A UNIQUE TESTBED FOR FUTURE RESEARCHERS INTERESTED IN SPEECH AND AGING.

PUBLIC AND INDIAN HOUSING

PUBLIC AND INDIAN HOUSING

PUBLIC AND INDIAN HOUSING

CAPITAL AND MANAGEMENT ACTIVITIES (FORMULA)

PUBLIC AND INDIAN HOUSING

ENHANCEMENT OF MECHANICAL PROPERTIES OF CARBON NANOTUBE FIBRES THROUGH THE IDENTIFICATION AND ELIMINATION OF

PUBLIC AND INDIAN HOUSING

AUTOMATED ASSESSMENT OF VISUOMOTOR FUNCTION IN CHILDREN WITH BRAIN INJURY

PUBLIC AND INDIAN HOUSING

PUBLIC AND INDIAN HOUSING

PUBLIC AND INDIAN HOUSING

PUBLIC AND INDIAN HOUSING

RESTORATIVE NEUROIMMUNOLOGY IN EXPERIMENTAL MODELS OF MULTIPLE SCLEROSIS VIA DIRECTLY INDUCED NEURAL STEM CELL TRANSPLANTATION (MS_INSC)

ADVANCED, MULTI-FUNCTION, INVERTED CONFOCAL MICROSCOPE FOR BNI STRUCTURAL AND FUNCTIONAL IMAGING CORE

UNDERSTANDING AND IMPROVING HIGH PERFORMANCE CARBON NANOTUBE FIBER

PUBLIC AND INDIAN HOUSING

PUBLIC CHARTER SCHOOLS

EQUILIBRIUM AND NON-EQUILIBRIUM CONDENSATION PHENOMENA IN A TUNEABLE HOMOGENEOUS BOSE GAS

STRUCTURAL MECHANISMS FOR THE INHIBITION OF THROMBOSIS

NON-INVASIVE STIMULATION FOR IMPROVING MOTOR FUNCTION IN SPINAL CORD INJURY

EFFICIENT FILTERING, TRACKING AND FUSION ALGORITHMS FOR LEGACY AND EMERGING RADAR SYSTEMS

PERFORM FUNDING SYS

PUBLIC AND INDIAN HOUSING

PERFORM FUNDING SYS

ADVANCED MATERIALS FOR SAFE AND EFFECTIVE STIMULATION OF THE RAT CERVICAL SPINAL CORD

TWO 30-TON MOBILE CRANES, TWO FORKLIFTS

PURPOSE: THE PUBLIC HOUSING OPERATING FUND (PH OPFUND) PROVIDES OPERATING SUBSIDIES TO HOUSING AUTHORITIES (HAS) TO ASSIST IN FUNDING THE OPERATING AND MAINTENANCE EXPENSES OF THEIR DWELLINGS, IN ACCORDANCE WITH SECTION 9 OF THE U.S. HOUSING ACT OF 1937, AS AMENDED. THE SUBSIDIES ARE REQUIRED TO HELP MAINTAIN SERVICES AND PROVIDE MINIMUM OPERATING RESERVES. THE PH OPFUND IS A $5 BILLION DOLLAR PROGRAM PROVIDING FUNDING TO APPROXIMATELY 6,000 HAS SERVING 1,590,321 PUBLIC HOUSING RESIDENTS IN 902,436 HOUSEHOLDS (44% ARE ELDERLY AND 35% OF RESIDENTS HAVE CHILDREN). INFORMATION ON THE CURRENT OPERATING FUND GRANT PROCESSING CAN BE FOUND AT HTTPS://WWW.HUD.GOV/PROGRAM_OFFICES/PUBLIC_INDIAN_HOUSING/PROGRAMS/PH/AM/FUNDING.; ACTIVITIES TO BE PERFORMED: OPERATING FUNDS ARE USED TO FUND DAY-TO-DAY OPERATIONAL EXPENSES ASSOCIATED WITH PUBLIC HOUSING AS WELL AS THE ADMINISTRATIVE AND PROGRAM IMPLEMENTATION EXPENSES THAT PUBLIC HOUSING AGENCIES (PHAS) ARE REQUIRED TO UNDERTAKE UNDER THE 1937 HOUSING ACT AND PROGRAM REGULATIONS. SUCH ACTIVITIES INCLUDE MANAGEMENT AND OPERATIONS, ROUTINE AND PREVENTATIVE MAINTENANCE, ANTI-CRIME, ANTI-DRUG AND SECURITY ACTIVITIES, OPERATING COSTS FOR PRIVATELY OWNED PUBLIC HOUSING UNITS WITHIN MIXED-FINANCE PROJECTS, ENERGY COSTS, RESIDENT SUPPORTIVE SERVICES, INSURANCE, DEBT SERVICE AND COSTS ASSOCIATED WITH ADMINISTRATION AND PROGRAM IMPLEMENTATION. TURNKEY III PROJECTS ARE FUNDED FOR UNITS UNDER THE FINAL LEASE PURCHASE AGREEMENT FOR CLOSING OUT THE PROGRAM. TO SUPPORT THESE ACTIVITIES, THERE IS CONTINUED MODERNIZATION OF THE INFORMATION TECHNOLOGY PLATFORMS. PHAS HAVE ACCESS TO WEB-BASED PLATFORMS THAT UTILIZE REAL-TIME DATA TO PROVIDE INSIGHT INTO THEIR PORTFOLIOS. PHAS CAN OBTAIN METRICS ON THEIR FUNDING LEVELS, OCCUPANCY RATES, AND THE NUMBER OF FAMILIES SERVED THROUGH RENTAL ASSISTANCE.; EXPECTED OUTCOMES: AS A RESULT OF THE ACTIVITIES PERFORMED, THIS PROGRAM IS EXPECTED TO ASSIST IN FUNDING THE OPERATING AND MAINTENANCE EXPENSES. THIS MAY INCLUDE INCREASED OCCUPANCY IN PUBLIC HOUSING, DECREASED ENERGY COSTS THROUGH REGULAR MAINTENANCE AND ENERGY PERFORMANCE CONTRACTING AND LEVERAGE FEDERAL RESOURCES. IN ADDITION TO ADDRESSING THE DEPARTMENT’S STRATEGIC GOALS OF: • ADDRESSING THE NEED FOR QUALITY AFFORDABLE RENTAL HOMES BY MAINTAINING OR IMPROVING UPON THE 96% OCCUPANCY RATE OF HABITABLE UNITS; • PROMOTING HOUSING AS A PLATFORM TO IMPROVE QUALITY OF LIFE THROUGH SUPPORTIVE SERVICES, CRIME PREVENTION EFFORTS AND RESIDENT ENGAGEMENT ACTIVITIES; AND • HELPING TO BUILD INCLUSIVE COMMUNITIES FREE FROM DISCRIMINATION BY FACILITATING THE IMPLEMENTATION OF AFFIRMATIVELY FURTHERING FAIR HOUSING MEASURES.; INTENDED BENEFICIARIES: THE OPERATING FUND PROVIDES FOR THE OPERATION AND MAINTENANCE OF LOW-INCOME HOUSING PROJECTS TO PHAS/PROJECTS. IT WAS CREATED TO ASSIST HOUSING AUTHORITIES IN PROVIDING DECENT AND SAFE RENTAL HOUSING FOR ELIGIBLE LOW-INCOME FAMILIES OR INDIVIDUALS, THE ELDERLY, AND PERSONS WITH DISABILITIES. A HA DETERMINES ELIGIBILITY BASED ON 1) ANNUAL GROSS INCOME; 2) A PERSON ON WHO IS ELDERLY, A PERSON WITH A DISABILITY, OR AS A FAMILY; AND 3) U.S. CITIZENSHIP OR ELIGIBLE IMMIGRATION STATUS.; SUBRECIPIENT ACTIVITIES: THE SUBRECIPIENT ACTIVITIES ARE UNKNOWN AT THE TIME OF AWARD.

ELUCIDATING AND TARGETING CLONAL LINEAGES INFLUENCING RESISTANCE TO THERAPY IN DISTINCT MUTATIONAL SUBTYPES OF HIGH-GRADE OVARIAN SEROUS CARCINOMA

ROLE OF SPARC IN WOUND HEALING AFTER SPINAL CORD INJURY - PROJECT SUMMARY: SPINAL CORD INJURY (SCI) TRIGGERS A CELLULAR AND EXTRACELLULAR MATRIX (ECM) REMODELING RESPONSE TO CLOSE THE WOUND. THIS RESPONSE IS DRIVEN LARGELY BY ASTROCYTES FORMING A PROTECTIVE BORDER AROUND INFILTRATING CELLS. THIS PROCESS IS INCOMPLETE IN MOST MAMMALS, FAILING TO RESTORE GROWTH PROMOTING SUBSTRATES, AND LEADING TO EXCESSIVE FIBROSIS. FIBROSIS AFTER SCI IS CHARACTERIZED BY THE SECRETION AND DEPOSITION OF ECM COMPONENTS (EG. COLLAGEN) AND THE ESTABLISHMENT OF A CHRONIC SCAR, IN WHICH CONNECTIVE TISSUE REPLACES NORMAL PARENCHYMA. CONSERVED ROLES FOR NON-NEURAL WOUND HEALING MECHANISMS HAVE BEEN IDENTIFIED IN THE ASTROCYTE RESPONSE TO SCI, BUT THE MOLECULAR CUES THAT DRIVE FIBROSIS AFTER SCI ARE NOT FULLY CHARACTERIZED AND REPRESENT A CRITICAL GAP IMPEDING THE DEVELOPMENT OF STRATEGIES TO IMPROVE SPINAL CORD WOUND HEALING. THE LONG-TERM GOAL IS TO DEVELOP THERAPIES THAT PROMOTE WOUND CLOSURE AND LIMIT FIBROTIC PROCESSES THAT LEAD TO PERSISTENT SCARRING. SPARC (SECRETED PROTEIN ACIDIC AND CYSTEINE RICH) IS A CENTRAL MODULATOR OF BOTH WOUND HEALING AND FIBROSIS. THERE IS A ROBUST AND PERSISTENT INCREASE IN SPARC PROTEIN EXPRESSION IN BORDER-ASSOCIATED ASTROCYTES AFTER SCI AND CONSTITUTIVE KNOCKOUT OF SPARC IMPAIRS WOUND HEALING AND IMPACTS BOTH CELLULAR AND EXTRACELLULAR REMODELING. THE OVERALL OBJECTIVE OF THIS PROPOSAL IS TO DETERMINE THE ROLE OF ASTROCYTIC SPARC SIGNALING IN THE STRUCTURAL AND FUNCTIONAL RESPONSES TO SCI. THE CENTRAL HYPOTHESIS IS THAT ASTROCYTIC SPARC HAS AN ACUTE, EARLY, PRO-WOUND HEALING ROLE AND A SUB-ACUTE, LATE, PRO-FIBROTIC ROLE FOLLOWING SCI. THE FOLLOWING TWO SPECIFIC AIMS ARE PROPOSED: 1) CHARACTERIZE THE TEMPORAL ROLES OF ASTROCYTIC SPARC IN WOUND REMODELING FOLLOWING SCI; 2) DETERMINE THE EFFECT OF ACUTE AND SUB-ACUTE SPARC DELETION IN ASTROCYTES ON FUNCTIONAL RECOVERY AFTER SCI. THE APPROACH IN AIM 1 WILL BE TO TARGET ACUTE AND SUB-ACUTE SPARC EXPRESSION IN ASTROCYTES USING TEMPORAL CONTROL IN A CONDITIONAL KNOCKOUT MOUSE MODEL TO EVALUATE CELLULAR RESPONSES AND ECM COMPOSITION FOLLOWING CONTUSIVE SCI. IN AIM 2, THE APPROACH WILL BE TO ASSESS SENSORY AND MOTOR RECOVERY IN CONTROL AND ASTROCYTE-SPECIFIC CONDITIONAL KNOCKOUT MICE WITH ACUTE OR SUB-ACUTE SPARC DELETION FOLLOWING CONTUSIVE SCI. THE PROPOSED RESEARCH IS INNOVATIVE IN THAT IT CENTERS ON DEFINING THE TEMPORAL AND CELL-TYPE SPECIFICITY FOR A KEY DRIVER OF EPITHELIAL WOUND HEALING AND FIBROSIS IN THE CONTEXT OF SCI, CONNECTING THE FIELDS OF NON-NEURAL AND NEURAL WOUND HEALING. THE PROPOSED STUDIES ARE SIGNIFICANT AS AN UNDERSTANDING OF CONSERVED ROLES FOR NON- NEURAL WOUND HEALING PATHWAYS AFTER SCI, MAY LEAD TO THE DEVELOPMENT OF NEW THERAPEUTIC APPROACHES TO ALTER SCI PROGRESSION, ENHANCE REMODELING, AND LIMIT PATHOLOGICAL SCARRING. THE EXPECTATION IS THAT COMPLETION OF THE PROPOSED STUDIES WILL DETERMINE THE ROLE OF ASTROCYTE-DERIVED SPARC IN WOUND HEALING AND FIBROSIS AFTER SCI. THE IDENTIFICATION OF NEW REGULATORS OF WOUND HEALING AND FIBROSIS WILL ALLOW FOR THE SUBSEQUENT DEVELOPMENT OF THERAPIES TO INCREASE REPAIR BY REDUCING THE GROWTH-RESTRICTIVE ENVIRONMENT AFTER SCI.

USING NATURAL MOUSE MOVEMENT TO ESTABLISH A DEVELOPMENTAL "BIOMARKER" FOR CORTICOSPINAL DAMAGE - THE CORTICOSPINAL TRACT (CST) IS A CRITICAL CIRCUIT UNDERLYING SKILLED VOLUNTARY MOVEMENTS. DAMAGE TO THIS CIRCUIT DURING DEVELOPMENT CAN CAUSE PERMANENT, LONG-TERM MOVEMENT DISABILITY IN HUMANS. RECOGNIZING AND TREATING SUCH DEVELOPMENTAL CST DAMAGE IS CHALLENGING, LARGELY BECAUSE IMMEDIATELY AFTER THE LESION, THERE ARE LIMITED OR ALMOST NO FUNCTIONAL DEFICITS. HOWEVER, EARLY RECOGNITION AND INTERVENTION WITH THE APPROPRIATE TREATMENT MEASURES IS KEY TO REDUCING LONG-TERM DISABILITY. THE USE OF PRECLINICAL MOUSE MODELS, WHICH HAVE OTHERWISE PROVEN TO BE HIGHLY USEFUL IN FUNCTIONAL INVESTIGATIONS OF NERVOUS SYSTEM DEVELOPMENT, HAS BEEN LIMITED IN THIS REGARD. SINCE THE CST IS KNOWN TO CONTROL SKILLED MOVEMENTS, ESTABLISHED BEHAVIORAL TESTS IN MICE THAT INVESTIGATE CST FUNCTION REQUIRE TRAINING MICE IN SKILLED TASKS. THIS PRECLUDES THEIR APPLICATION IN NEONATAL MICE. FURTHER, MOUSE MODELS USED TO INVESTIGATE DEVELOPMENTAL CST DAMAGE, E.G. NEONATAL HYPOXIA OR SPINAL INJURIES, DO NOT ONLY DAMAGE THE CST; RATHER THEY DISRUPT MULTIPLE NEURAL PATHWAYS. IT THEREFORE REMAINS COMPLETELY UNKNOWN WHETHER THE CST CONTRIBUTES ONLY TO SKILLED MOVEMENTS IN ADULT MICE, OR WHETHER IT ALSO CONTRIBUTES TO THE DEVELOPMENT OF NATURAL, INNATE MOTOR ABILITY DURING DEVELOPMENT, BEGINNING IN NEONATAL MICE. THIS LATTER POSSIBILITY WOULD SUGGEST THAT THERE ARE EARLY, ALBEIT SUBTLE, BEHAVIORAL CORRELATES OF DEVELOPMENTAL CST INJURY IN MICE. WE RECENTLY DEVELOPED A NEW MICROSURGICAL APPROACH TO SPECIFICALLY DISRUPT THE DEVELOPING CST IN NEONATAL MICE. IN ADDITION, WE HAVE ALSO ESTABLISHED THE USE OF MOTION SEQUENCING (MOSEQ), A NEW MACHINE LEARNING AND ARTIFICIAL INTELLIGENCE PLATFORM, TO LONGITUDINALLY INVESTIGATE THE DEVELOPMENT OF NATURAL MOVEMENTS IN NEONATAL MICE. OUR PRELIMINARY RESULTS USING MOSEQ SUGGEST THAT DEVELOPMENTAL DAMAGE TO THE CST RESULTS IN SPECIFIC CHANGES TO MOVEMENT STRUCTURES IN MICE, AS EARLY AS P12; THESE EXTEND INTO MATURITY AT P35. FURTHER, ANALYSIS OF THESE P35 MICE USING CONVENTIONAL METRICS OF LOCOMOTION SUCH AS THE CATWALK, DID NOT IDENTIFY ANY DEFICITS, HIGHLIGHTING THE SENSITIVITY OF MOSEQ IN IDENTIFYING CHANGES IN MOUSE MOVEMENTS. THIS PROPOSAL INVESTIGATES THE HYPOTHESIS THAT THE CST CONTROLS DEVELOPMENT OF NATURAL MOUSE MOVEMENTS, AND NOT ONLY SKILLED MOVEMENTS AT MATURITY. WE WILL USE MOSEQ TO ANALYZE FEZF2 KNOCK OUT (FEZF2 KO) MICE IN WHICH THE CST IS NEVER ESTABLISHED DURING DEVELOPMENT (AIM1), AS WELL AS MICE THAT UNDERGO MICROSURGICAL LESIONS TO DISRUPT SPINAL CONNECTIVITY OF THE CST AT DISTINCT DEVELOPMENTAL TIMES (AIM2). TOGETHER, OUR WORK WILL IDENTIFY NOVEL FUNCTIONAL READOUTS OF DEVELOPMENTAL DAMAGE TO THE CST USING NATURAL MOUSE MOVEMENTS. THIS NEW UNBIASED QUANTITATIVE APPROACH TOWARD INVESTIGATING THE EARLIEST BEHAVIORAL SIGNS OF CORTICOSPINAL DYSFUNCTION IN MICE WHICH WILL HAVE EVENTUAL APPLICATION IN INVESTIGATIONS OF DESCENDING CIRCUITS OF MOTOR CONTROL, AS WELL AS MULTIPLE PRECLINICAL MODELS OF DEVELOPMENTAL DAMAGE SUCH AS NEONATAL HYPOXIA OR SPINAL INJURIES.

LOSS OF A COHORT OF AXONAL MRNAS AS A RESULT OF REDUCED SMN LEVELS.

CAPITAL FUND PROGRAM

CAPITAL FUND PROGRAM

THE MECHANISM OF LOW DOSE RADIATION RISK ASSOCIATED WITH DIAGNOSTIC X-RAYS AND GAMMA-RAYS

CAPITAL FUND PROGRAM

TRANSCRANIAL DIRECT CURRENT STIMULATION AND MOTOR TRAINING IN CHRONIC STROKE

TAS::57 3600::TAS NEUROMOD

ELECTRON AND ION MICROSCOPY AND NANOFABRICATION OF METAMATERIALS SUPERLATTICES FOR IR APPLICATIONS

THE MECHANICS OF PENETRATION OF POLYETHYLENE BASED COMPOSITES

NICKEL BONDED TIC COMPOSITES FOR DYNAMIC BLAST MITIGATION APPLICATIONS

TAS::57 3600::TAS 'METALIZATION OF CNT FIBRES' DATED 31 MAY 2017

NICOP - DYNAMIC PERFORMANCE OF 3D ASSEMBLED COMPOSITE STRUCTURES

REAP RENEWABLE ENERGY SYSTEM (RES) GRANT UNRESTRICTED AMOUNT

NICOP - THERMAL PERFORMANCE OF CARBON NANOTUBES IN THE FORM OF CABLES AND WOVEN FABRICS

DISSECTING OVARIAN CANCER TUMOR-IMMUNE MICROENVIRONMENTS THROUGH 3D IN SITU MOLECULAR PROFILING

PUBLIC HOUSING CAPITAL FUND

TO FOSTER EFFICIENCY COMPETITIVE OPERATIONS AND QUALITY SHIP CONSTRUCTION REPAIR AND RECONFIGURATION IN SMALL SHIPYARDS ACROSS THE UNITED STATES IN ADDITION TO FOSTERING EMPLOYEE SKILLS AND ENHANCED PRODUCTIVITY RELATED TO SHIPBUILDING SHIP REPAIR AND ASSOCIATED INDUSTRIES THIS GRANT IS FOR THE PURCHASE AND INSTALLATION AN PROCUREMENT AND INTEGRATION OF TRAINING EQUIPMENT AND TECHNOLOGIES DELIVERABLES ARE ANPROCUREMENT AND INTEGRATION OF TRAINING EQUIPMENT AND TECHNOLOGIES - ELECTRO HYDROSTATIC TEST PUMPS MILLER XMT 400 WELDING MACHINES MILLER ALUMAFEED 350 MILLER CST 282 208-575V TWECO PWI ULTRILITE TELESCOPING GANTRY CRANE TEXAS METAL WORKS MODPRO WELDING BOOTHS SCOTCHMAN 65 TON IRONWORKER SCOTCHMAN HYDRAULIC PRESS PRESSPRO 110W BALEIGH RBD-500 PIPE BENDER RIDGID PIPE THREADING MACHINE - 3RY43|535 JET HBS1220DC SEMI-AUTOMATIC DUAL COLUMN BANDSAW RIDGID ADJUSTABLE PIPE STAND WITH 2 ADJUSTABLE ROLLERS RIDGID PORTABLE CHAIN VISE WILTON 28814 MODEL 8100M MECHANICS PRO VISE HEAVY DUTY GRAVITY ROLLER CONVEYORS PALLET RACKS WHICH WILL INCREASE EFFICIENCY IN WITHIN THE SHIPYARD INTENDED BENEFICIARY IS MASTER BOAT BUILDERS THERE ARE NO SUBRECIPIENT ACTIVITIES

REAP RENEWABLE ENERGY SYSTEM (RES) GRANT UNRESTRICTED AMOUNT

DEVELOPING MULTI-PHASE SINGLE WALL CNT FIBERS

PUBLIC HOUSING CAPITAL FUND

NEW APPROACHES TO MODELLING THERMO-CHEMO-MECHANICAL COUPLINGS IN HOT CORROSION

IMPROVING OUTCOMES IN PHARMACOTHERAPHY OF SOCIAL PHOBIA

SEC. 9007 REAP-RENEW ENERGY SYS GRANTS (MAN)

CAPITAL FUND PROGRAM

WASTE DISPOSAL GRANTS - REGULAR

CAPITAL FUND PROGRAM

PUBLIC HOUSING CAPITAL FUND

THE MECHANICS OF THE DYNAMIC RESPONSE OF CELLULAR CORE SANDWICH STRUCTURES

THE ROLE OF THE INTESTINAL MICROBIOME IN ANXIETY AND DEPRESSION

DESIGNING NOVEL STRATEGIES TO TARGET TUMOR-PROMOTING FUNCTIONS OF PANCREATIC CANCER FIBROBLAST SUBTYPES

ELUCIDATING AND TARGETING CLONAL LINEAGES INFLUENCING RESISTANCE TO THERAPY IN DISTINCT MUTATIONAL SUBTYPES OF HIGH-GRADE OVARIAN SEROUS CARCINOMA

PURPOSE: THE PUBLIC HOUSING OPERATING FUND (PH OPFUND) PROVIDES OPERATING SUBSIDIES TO HOUSING AUTHORITIES (HAS) TO ASSIST IN FUNDING THE OPERATING AND MAINTENANCE EXPENSES OF THEIR DWELLINGS, IN ACCORDANCE WITH SECTION 9 OF THE U.S. HOUSING ACT OF 1937, AS AMENDED. THE SUBSIDIES ARE REQUIRED TO HELP MAINTAIN SERVICES AND PROVIDE MINIMUM OPERATING RESERVES. THE PH OPFUND IS A $5 BILLION DOLLAR PROGRAM PROVIDING FUNDING TO APPROXIMATELY 6,000 HAS SERVING 1,590,321 PUBLIC HOUSING RESIDENTS IN 902,436 HOUSEHOLDS (44% ARE ELDERLY AND 35% OF RESIDENTS HAVE CHILDREN). INFORMATION ON THE CURRENT OPERATING FUND GRANT PROCESSING CAN BE FOUND AT HTTPS://WWW.HUD.GOV/PROGRAM_OFFICES/PUBLIC_INDIAN_HOUSING/PROGRAMS/PH/AM/FUNDING.; ACTIVITIES TO BE PERFORMED: OPERATING FUNDS ARE USED TO FUND DAY-TO-DAY OPERATIONAL EXPENSES ASSOCIATED WITH PUBLIC HOUSING AS WELL AS THE ADMINISTRATIVE AND PROGRAM IMPLEMENTATION EXPENSES THAT PUBLIC HOUSING AGENCIES (PHAS) ARE REQUIRED TO UNDERTAKE UNDER THE 1937 HOUSING ACT AND PROGRAM REGULATIONS. SUCH ACTIVITIES INCLUDE MANAGEMENT AND OPERATIONS, ROUTINE AND PREVENTATIVE MAINTENANCE, ANTI-CRIME, ANTI-DRUG AND SECURITY ACTIVITIES, OPERATING COSTS FOR PRIVATELY OWNED PUBLIC HOUSING UNITS WITHIN MIXED-FINANCE PROJECTS, ENERGY COSTS, RESIDENT SUPPORTIVE SERVICES, INSURANCE, DEBT SERVICE AND COSTS ASSOCIATED WITH ADMINISTRATION AND PROGRAM IMPLEMENTATION. TURNKEY III PROJECTS ARE FUNDED FOR UNITS UNDER THE FINAL LEASE PURCHASE AGREEMENT FOR CLOSING OUT THE PROGRAM. TO SUPPORT THESE ACTIVITIES, THERE IS CONTINUED MODERNIZATION OF THE INFORMATION TECHNOLOGY PLATFORMS. PHAS HAVE ACCESS TO WEB-BASED PLATFORMS THAT UTILIZE REAL-TIME DATA TO PROVIDE INSIGHT INTO THEIR PORTFOLIOS. PHAS CAN OBTAIN METRICS ON THEIR FUNDING LEVELS, OCCUPANCY RATES, AND THE NUMBER OF FAMILIES SERVED THROUGH RENTAL ASSISTANCE.; EXPECTED OUTCOMES: AS A RESULT OF THE ACTIVITIES PERFORMED, THIS PROGRAM IS EXPECTED TO ASSIST IN FUNDING THE OPERATING AND MAINTENANCE EXPENSES. THIS MAY INCLUDE INCREASED OCCUPANCY IN PUBLIC HOUSING, DECREASED ENERGY COSTS THROUGH REGULAR MAINTENANCE AND ENERGY PERFORMANCE CONTRACTING AND LEVERAGE FEDERAL RESOURCES. IN ADDITION TO ADDRESSING THE DEPARTMENT’S STRATEGIC GOALS OF: • ADDRESSING THE NEED FOR QUALITY AFFORDABLE RENTAL HOMES BY MAINTAINING OR IMPROVING UPON THE 96% OCCUPANCY RATE OF HABITABLE UNITS; • PROMOTING HOUSING AS A PLATFORM TO IMPROVE QUALITY OF LIFE THROUGH SUPPORTIVE SERVICES, CRIME PREVENTION EFFORTS AND RESIDENT ENGAGEMENT ACTIVITIES; AND • HELPING TO BUILD INCLUSIVE COMMUNITIES FREE FROM DISCRIMINATION BY FACILITATING THE IMPLEMENTATION OF AFFIRMATIVELY FURTHERING FAIR HOUSING MEASURES.; INTENDED BENEFICIARIES: THE OPERATING FUND PROVIDES FOR THE OPERATION AND MAINTENANCE OF LOW-INCOME HOUSING PROJECTS TO PHAS/PROJECTS. IT WAS CREATED TO ASSIST HOUSING AUTHORITIES IN PROVIDING DECENT AND SAFE RENTAL HOUSING FOR ELIGIBLE LOW-INCOME FAMILIES OR INDIVIDUALS, THE ELDERLY, AND PERSONS WITH DISABILITIES. A HA DETERMINES ELIGIBILITY BASED ON 1) ANNUAL GROSS INCOME; 2) A PERSON ON WHO IS ELDERLY, A PERSON WITH A DISABILITY, OR AS A FAMILY; AND 3) U.S. CITIZENSHIP OR ELIGIBLE IMMIGRATION STATUS.; SUBRECIPIENT ACTIVITIES: THE SUBRECIPIENT ACTIVITIES ARE UNKNOWN AT THE TIME OF AWARD.

CAPITAL FUND PROGRAM

THE PURPOSE OF THIS GRANT IS TO FUND RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY DARPA MECHANICALLY INTERLOCKED MATERIALS MIMS PROGRAM. THIS EFFORT SHALL BE CARRIED OUT GENERALLY AS SET FORTH IN EXHIBIT B, RESEARCH DESCRIPTION DOCUMENT, DATED SEPTEMBER 5, 2023, AND IN THE RECIPIENTS PROPOSAL TITLED, NOVEL SYNTHETIC SYSTEMS FOR SCALABLE POLY N CATENANES AND MECHANICALLY INTERLOCKED MATERIALS, DATED APRIL 17, 2022, AND REVISED COST PROPOSAL DATED OCTOBER 4, 2023, COPIES OF WHICH ARE IN THE POSSESSION OF BOTH PARTIES.

PURPOSE: THE VOLUNTEER INCOME TAX ASSISTANCE (VITA) GRANT WAS ESTABLISHED AS A MATCHING GRANT PROGRAM TO PROVIDE FUNDING FOR ORGANIZATIONS WHO SUPPORT COMMUNITY VOLUNTEER INCOME TAX ASSISTANCE. ACTIVITIES TO BE PERFORMED: THE VITA GRANT PROGRAM PROVIDES FINANCIAL SUPPORT TO ORGANIZATIONS WHO 1) EXTEND SERVICES TO UNDERSERVED POPULATIONS IN HARDEST TO REACH AREAS BOTH URBAN AND NON-URBAN; 2) INCREASE THE CAPACITY TO FILE RETURNS ELECTRONICALLY; 3) HEIGHTEN QUALITY CONTROL; 4) ENHANCE TRAINING OF VOLUNTEERS; AND 5) SIGNIFICANTLY IMPROVE THE ACCURACY RATE OF RETURNS PREPARED AT VITA SITES. END GOAL/EXPECTED OUTCOMES: VITA GRANT RECIPIENTS ARE EXPECTED TO 1) FOLLOW EXISTING GUIDANCE GOVERNING VITA SITE OPERATIONS; 2) ENSURE AT LEAST 90% OF RETURNS PREPARED ARE FOR INDIVIDUALS WHOSE INCOME IS EQUAL TO OR LESS THAN THE MAXIMUM EARNED INCOME TAX CREDIT (EITC) THRESHOLDS; 2) FILE ALL ELIGIBLE RETURNS ELECTRONICALLY; 3) ACHIEVE 100% OF THEIR RETURN PRODUCTION GOALS; 4) BECOME MORE EFFICIENT WITH GRANT FUNDS; AND 5) SHOW INCREMENTAL INCREASES IN RETURN PREPARATION EACH YEAR. INTENDED BENEFICIARIES: TAXPAYERS WHO ARE LOW TO MODERATE INCOME INDIVIDUALS, PERSONS WITH DISABILITIES, THOSE FOR WHOM ENGLISH IS A SECOND LANGUAGE, NATIVE AMERICANS, INDIVIDUALS LIVING IN RURAL AREAS, MEMBERS OF THE ARMED FORCES AND THEIR FAMILIES, AND THE ELDERLY. SUBRECIPIENT ACTIVITIES: SUBRECIPIENTS MAY BE UTILIZED BY GRANT RECIPIENTS TO HELP DELIVER KEY ELEMENTS OF THE PROGRAM AND MUST ADHERE TO GRANT PROGRAM GUIDELINES. BROADBAND: SPECIFIC ACTIVITIES RELATING TO BROADBAND USAGE ARE NOT KNOWN AT THE TIME OF AWARD.

ATTENTIVE STATE SPACE MODELING OF DYNAMICAL SYSTEMS

PURPOSE: THE VOLUNTEER INCOME TAX ASSISTANCE (VITA) GRANT WAS ESTABLISHED AS A MATCHING GRANT PROGRAM TO PROVIDE FUNDING FOR ORGANIZATIONS WHO SUPPORT COMMUNITY VOLUNTEER INCOME TAX ASSISTANCE. ACTIVITIES TO BE PERFORMED: THE VITA GRANT PROGRAM PROVIDES FINANCIAL SUPPORT TO ORGANIZATIONS WHO 1) EXTEND SERVICES TO UNDERSERVED POPULATIONS IN HARDEST TO REACH AREAS BOTH URBAN AND NON-URBAN; 2) INCREASE THE CAPACITY TO FILE RETURNS ELECTRONICALLY; 3) HEIGHTEN QUALITY CONTROL; 4) ENHANCE TRAINING OF VOLUNTEERS; AND 5) SIGNIFICANTLY IMPROVE THE ACCURACY RATE OF RETURNS PREPARED AT VITA SITES. END GOAL/EXPECTED OUTCOMES: VITA GRANT RECIPIENTS ARE EXPECTED TO 1) FOLLOW EXISTING GUIDANCE GOVERNING VITA SITE OPERATIONS; 2) ENSURE AT LEAST 90% OF RETURNS PREPARED ARE FOR INDIVIDUALS WHOSE INCOME IS EQUAL TO OR LESS THAN THE MAXIMUM EARNED INCOME TAX CREDIT (EITC) THRESHOLDS; 2) FILE ALL ELIGIBLE RETURNS ELECTRONICALLY; 3) ACHIEVE 100% OF THEIR RETURN PRODUCTION GOALS; 4) BECOME MORE EFFICIENT WITH GRANT FUNDS; AND 5) SHOW INCREMENTAL INCREASES IN RETURN PREPARATION EACH YEAR. INTENDED BENEFICIARIES: TAXPAYERS WHO ARE LOW TO MODERATE INCOME INDIVIDUALS, PERSONS WITH DISABILITIES, THOSE FOR WHOM ENGLISH IS A SECOND LANGUAGE, NATIVE AMERICANS, INDIVIDUALS LIVING IN RURAL AREAS, MEMBERS OF THE ARMED FORCES AND THEIR FAMILIES, AND THE ELDERLY. SUBRECIPIENT ACTIVITIES: SUBRECIPIENTS MAY BE UTILIZED BY GRANT RECIPIENTS TO HELP DELIVER KEY ELEMENTS OF THE PROGRAM AND MUST ADHERE TO GRANT PROGRAM GUIDELINES. BROADBAND: SPECIFIC ACTIVITIES RELATING TO BROADBAND USAGE ARE NOT KNOWN AT THE TIME OF AWARD.

PURPOSE: THE VOLUNTEER INCOME TAX ASSISTANCE (VITA) GRANT WAS ESTABLISHED AS A MATCHING GRANT PROGRAM TO PROVIDE FUNDING FOR ORGANIZATIONS WHO SUPPORT COMMUNITY VOLUNTEER INCOME TAX ASSISTANCE. ACTIVITIES TO BE PERFORMED: THE VITA GRANT PROGRAM PROVIDES FINANCIAL SUPPORT TO ORGANIZATIONS WHO 1) EXTEND SERVICES TO UNDERSERVED POPULATIONS IN HARDEST TO REACH AREAS BOTH URBAN AND NON-URBAN; 2) INCREASE THE CAPACITY TO FILE RETURNS ELECTRONICALLY; 3) HEIGHTEN QUALITY CONTROL; 4) ENHANCE TRAINING OF VOLUNTEERS; AND 5) SIGNIFICANTLY IMPROVE THE ACCURACY RATE OF RETURNS PREPARED AT VITA SITES. END GOAL/EXPECTED OUTCOMES: VITA GRANT RECIPIENTS ARE EXPECTED TO 1) FOLLOW EXISTING GUIDANCE GOVERNING VITA SITE OPERATIONS; 2) ENSURE AT LEAST 90% OF RETURNS PREPARED ARE FOR INDIVIDUALS WHOSE INCOME IS EQUAL TO OR LESS THAN THE MAXIMUM EARNED INCOME TAX CREDIT (EITC) THRESHOLDS; 2) FILE ALL ELIGIBLE RETURNS ELECTRONICALLY; 3) ACHIEVE 100% OF THEIR RETURN PRODUCTION GOALS; 4) BECOME MORE EFFICIENT WITH GRANT FUNDS; AND 5) SHOW INCREMENTAL INCREASES IN RETURN PREPARATION EACH YEAR. INTENDED BENEFICIARIES: TAXPAYERS WHO ARE LOW TO MODERATE INCOME INDIVIDUALS, PERSONS WITH DISABILITIES, THOSE FOR WHOM ENGLISH IS A SECOND LANGUAGE, NATIVE AMERICANS, INDIVIDUALS LIVING IN RURAL AREAS, MEMBERS OF THE ARMED FORCES AND THEIR FAMILIES, AND THE ELDERLY. SUBRECIPIENT ACTIVITIES: SUBRECIPIENTS MAY BE UTILIZED BY GRANT RECIPIENTS TO HELP DELIVER KEY ELEMENTS OF THE PROGRAM AND MUST ADHERE TO GRANT PROGRAM GUIDELINES. BROADBAND: SPECIFIC ACTIVITIES RELATING TO BROADBAND USAGE ARE NOT KNOWN AT THE TIME OF AWARD.

NOVEL MYOFUNCTIONAL NIPPLE TO PREVENT OBSTRUCTIVE SLEEP APNEA IN INFANTS - PROJECT SUMMARY: THERE IS A CLEAR UNMET NEED TO PROVIDE A NON-INVASIVE AND NON-BURDENSOME FIRST LINE TREATMENT AND PREVENTIVE MEASURE FOR OBSTRUCTIVE SLEEP APNEA (OSA) IN INFANTS. ALTHOUGH OSA IN INFANTS TYPICALLY GOES UNDIAGNOSED, IT IS ESTIMATED THAT 1%-4% OF INFANTS SUFFER FROM OSA AFFECTING AS MANY AS 5.6 MILLION INFANTS WORLDWIDE EACH YEAR. OSA IN INFANT POPULATIONS CAN HAVE DETRIMENTAL IMPACTS ON LONG-TERM HEALTH, INCLUDING AN INCREASED RISK FOR OBESITY, DEVELOPMENTAL DELAYS, HYPERACTIVITY, INCREASED BLOOD PRESSURE, A GENERAL “FAILURE TO THRIVE,” AND EVEN ORGAN DAMAGE. LESS SEVERE FORMS OF SLEEP DISORDERED BREATHING (SDB) SUCH AS SNORING, WHICH IS PREVALENT IN 10% OF INFANTS, CAN BE ASSOCIATED WITH BEHAVIORAL ISSUES AND DIMINISHED COGNITIVE SKILLS WHICH CAN OVERALL DECREASE THE QUALITY OF LIFE OF THE INFANT. A FIRST LINE TREATMENT IN CHILDREN IS ADENOTONSILLECTOMY (A&T), A SURGICAL PROCEDURE THAT REMOVES TONSILS AND ADENOIDS. ALTHOUGH A&T CAN BE EFFECTIVE, IT IS AN INVASIVE PROCEDURE THAT, DUE TO RISK OF COMPLICATIONS, IS RARELY CONDUCTED ON INFANTS BELOW THE AGE OF ONE. CONTINUOUS POSITIVE AIR PRESSURE (CPAP) THERAPY, THE OTHER PROMINENT TREATMENT FOR OSA, OFTEN CAUSES ADDITIONAL ISSUES FOR INFANTS WHO ALREADY HAVE RESPIRATORY ISSUES, SUCH AS INCREASED VIRAL LOAD. MYOFUNCTIONAL THERAPY CONSISTING OF OROPHARYNGEAL EXERCISES IS A PROMISING NEW POTENTIAL FIRST LINE & NON-INVASIVE TREATMENT OF OSA FOR ADULTS AND CHILDREN. STUDIES HAVE SHOWN MYOFUNCTIONAL THERAPY TO DECREASE APNEA HYPOPNEA INDEX (AHI) BY 14.3 EVENTS/HOUR IN ADULTS, 3.0 EVENTS/HOUR (60% REDUCTION) IN CHILDREN, AND REDUCES RESIDUAL OSA IN CHILDREN AFTER A&T. HOWEVER, IT IS DIFFICULT FOR INFANTS TO LEARN AND PRACTICE BENEFICIAL MYOFUNCTIONAL EXERCISES. THERE IS CURRENTLY NO LOW RISK, LOW BURDEN DEVICE THAT CAN BE USED TO TREAT OSA IN INFANTS. MANY FAMILIES FEED THEIR CHILDREN WITH A BOTTLE STARTING IN THE FIRST SIX MONTHS OF THE CHILD’S LIFE, AND BABY BOTTLE USE DURING INFANCY CAN BE ASSOCIATED WITH AN INCREASED RISK FOR OSA WHEN COMPARED TO BREASTFEEDING: BREASTFEEDING BABIES EXERCISES OROPHARYNGEAL MUSCLES LIKE MYOFUNCTIONAL THERAPY DOES. HOWEVER, THERE ARE CURRENTLY NO BABY BOTTLES THAT INCORPORATE OROPHARYNGEAL EXERCISES INTO THE DAILY DRINKING AND FEEDING OF INFANTS. THERE IS A HUGE OPPORTUNITY TO DELIVER OROPHARYNGEAL EXERCISES TO IMPROVE OSA IN A BABY BOTTLE FORMAT. TO ADDRESS THE LACK OF LOW RISK AND LOW BURDEN SOLUTIONS FOR INFANT OSA, WE WILL DEVELOP AN INNOVATIVE MYOFUNCTIONAL THERAPY BABY BOTTLE NIPPLE AND THAT CAN BE EASILY ADMINISTERED TO INFANTS WITH OSA. THE SCIENTIFIC PREMISE OF THIS PROJECT IS THAT A NOVEL THERAPEUTIC MYO-NIPPLE THAT MIMICS BREASTFEEDING FORCES WILL BOTH REDUCE THE PREVALENCE OF INFANT OSA AND PREVENT THE LONG-TERM DEVELOPMENT OF OSA BY STIMULATING PROPER CRANIOFACIAL GROWTH AND OROFACIAL MUSCLE DEVELOPMENT. PARENTS AND CLINICIANS WILL BE INTERVIEWED TO UNDERSTAND THE REQUIREMENTS FOR SUCCESSFUL MARKET ENTRY OF THE BABY BOTTLE MYO- NIPPLE. THIS WILL BE FOLLOWED BY THE DEVELOPMENT OF A FUNCTIONAL MYO-NIPPLE PROTOTYPE THAT MEETS THE REQUIREMENTS FROM CLINICIANS AND PARENTS AND INCORPORATES DEFINED BREAST-LIKE OROPHARYNGEAL EXERCISES. THIS PROJECT SEEKS TO IMPROVE THE QUALITY OF LIFE FOR FUTURE GENERATIONS OF WOULD-BE OSA SUFFERERS AND PRIMARY SNORERS.

ATOMIC SCALE RESOLUTION IMAGING AND SPECTROSCOPY OF 2-D AND 2-D/3D MATERIALS FOR FUNCTIONAL APPLICATIONS

HORMONAL INFLUENCES ON NEURAL/BEHAVIORAL DEVELOPMENT

DOMESTIC WATER GRANTS - REGULAR

ALLOY DESIGN TO RESIST ENVIRONMENTAL ATTACK

ADAPTIVE HYBRID SIMULATIONS OF SOLVATED REACTIONS

PURPOSE: TO PROMOTE ECONOMIC REVITALIZATION AND COMMUNITY DEVELOPMENT THROUGH TECHNICAL ASSISTANCE AWARDS TO BUILD THE CAPACITY OF COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS (CDFIS) AND EMERGING CDFIS. PLANNED ACTIVITIES TECHNICAL ASSISTANCE MUST BE USED FOR THE FOLLOWING ELIGIBLE ACTIVITIES SUBJECT TO THE APPLICABLE PROVISIONS OF THE UNIFORM REQUIREMENTS COMPENSATION PERSONAL SERVICES, COMPENSATION FRINGE BENEFITS, PROFESSIONAL SERVICE COSTS, TRAVEL COSTS, TRAINING AND EDUCATION COSTS, EQUIPMENT, SUPPLIES, AND INCORPORATION COSTS (SPONSORING ENTITIES ONLY). END GOALS: THE GOAL OF THE TECHNICAL ASSISTANCE IS TO BUILD CERTIFIED AND EMERGING CDFI’S ORGANIZATIONAL CAPACITY TO SERVE ELIGIBLE MARKETS AND/OR THEIR TARGET MARKETS, IN ORDER TO SERVE LOW INCOME PEOPLE, AND COMMUNITIES ACROSS THE NATION THAT LACK ADEQUATE ACCESS TO AFFORDABLE FINANCIAL PRODUCTS AND FINANCIAL SERVICES. BENEFICIARIES: PROFIT ORGANIZATION, PRIVATE NONPROFIT INSTITUTION/ORGANIZATION, OTHER PRIVATE INSTITUTION/ORGANIZATION INVESTMENT AREAS AND TARGETED POPULATIONS, AS DEFINED IN 12 C.F.R. 1805. SUBRECIPIENTS: THERE ARE NO SUBRECIPIENTS FOR THIS PROGRAM. BROADBAND: NOT APPLICABLE. REASON/PURPOSE OF MODIFICATION: NOT APPLICABLE.

R&D, SCIENCE AND ENGINEERING, IN THE AREA OF METALLURGY AND MATERIALS

TAS::57 3600::TAS "EQUILIBRIUM AND NON-EQUILIBRIUM CONDENSATION PHENOMENA IN TUNEABLE 3D AND 2D BOSE GASES."

WAURIKA LAKE INTAKE IMPROVEMENT PROJECT

CAROL M. WHITE PHYSICAL EDUCATION PROGRAM

ROLE OF TRANSCRIPTION FACTOR ACTIVATING PROTEIN-2 BETA (AP-2?) IN CORNEAL EPITHELIAL CELL FATE DETERMINATION AND STRATIFICATION - CORNEAL SURFACE PATHOLOGIES SUCH AS CORNEAL CONJUNCTIVALIZATION ARISE MAINLY FROM THE LOSS OF LIMBAL EPITHELIAL STEM CELLS (LESCS) AND CAN LEAD TO CORNEAL NEOVASCULARIZATION, OPACITY AND ULTIMATELY, BLINDNESS. ALTHOUGH THE ROLE OF NEURAL CREST CELLS (NCC)-DERIVED PERIOCULAR MESENCHYME (POM) HAS BEEN ESTABLISHED IN DEVELOPMENT OF THE CORNEAL STROMA, ITS ROLE IN DEVELOPMENT OF THE CORNEAL LIMBUS AND CORNEAL EPITHELIUM HAS YET TO BE DETERMINED. IT HAS BEEN SHOWN THAT TRANSCRIPTION FACTORS INCLUDING ACTIVATING PROTEIN-2 BETA (AP-2SS) PLAY KEY ROLES IN THE DEVELOPMENT AND DIFFERENTIATION OF THE POM. HOWEVER, THE ROLE OF AP-2SS IN POM-MEDIATED CORNEAL EPITHELIAL DEVELOPMENT REMAINS LARGELY UNKNOWN, AS AP-2SS NULL MICE DIE SOON AFTER BIRTH. TO ADDRESS THIS, WE HAVE SPECIFICALLY DELETED AP-2SS IN THE NCC OF MICE, USING THE WNT1CRE-RECOMBINASE SYSTEM (AP-2SS NCC KO). TWO MAJOR DEFECTS OBSERVED IN THESE MICE WERE CORNEAL THINNING AND VASCULARIZATION AND CONTRIBUTING TO THIS PHENOTYPE WERE AN ABSENCE OF THE CORNEAL ENDOTHELIUM AND IMPAIRMENT IN CORNEAL EPITHELIAL STRATIFICATION. OUR SCRNA-SEQ ANALYSES ALONG WITH RNASCOPE AND IMMUNOHISTOCHEMISTRY REVEALED AN ABSENCE OF KERATIN-12 (K12), A CORNEAL EPITHELIAL MARKER, AND EXPANSION OF KERATIN-15 (K15) AND K13, CONJUNCTIVAL EPITHELIAL SPECIFIC MARKERS, INTO THE CORNEAL EPITHELIUM OF THE MUTANT WHEN COMPARED TO CONTROLS. FURTHER INVESTIGATIONS REVEALED AN ABSENCE OF ABCB5, A LESC MARKER, FROM THE LIMBAL REGION OF THE MUTANTS INDICATING A CONJUNCTIVAL-LIKE PHENOTYPE DUE TO THE ABSENCE OF AP-2SS IN THE NCC. IN ADDITION, BONE MORPHOGENETIC PROTEIN (BMP) 4, A KEY PLAYER IN CORNEAL MESENCHYMAL-TO-EPITHELIAL SIGNALING KNOWN TO BE MODULATED BY WNT/SS-CATENIN DURING CORNEAL EPITHELIAL STRATIFICATION, WAS ABSENT IN THE EPITHELIUM OF THE MUTANTS FURTHER SUGGESTING A CRUCIAL ROLE OF AP-2SS IN REGULATING CORNEAL EPITHELIAL CELL FATE AND STRATIFICATION. THUS, OUR OVERARCHING HYPOTHESIS IS THAT EXPRESSION OF AP-2SS IN THE POM IS CRITICAL FOR CORNEAL EPITHELIAL CELL FATE DETERMINATION AND STRATIFICATION THROUGH MODULATION OF THE WNT/SS-CATENIN SIGNALING PATHWAY. IN THE CURRENT PROPOSAL WE AIM TO DETERMINE: 1) THE DEVELOPMENTAL TIMING AND FATE OF LESC IN THE AP-2SS NCC KO MUTANTS AND 2) WHETHER WNT/SS-CATENIN/BMP4 –SIGNALING AXIS-IS DISRUPTED IN THE MUTANT AND CONTRIBUTES TO THE OCULAR SURFACE DEFECTS. OVERALL, THESE STUDIES WILL CONTRIBUTE TO OUR UNDERSTANDING OF THE GENE REGULATORY NETWORK (GRN) CONTROLLING CORNEAL EPITHELIAL CELL FATE DETERMINATION AND STRATIFICATION, AND THE PATHOGENESIS OF DISEASES MARKED BY CORNEAL THINNING, NEOVASCULARIZATION AND OPACIFICATION.

MOUNTAIN PARK MASTER CONSERVANCY DISTRICT IN SOUTHWEST OKLAHOMA SEEKS TO ESTABLISH AN EMERGENCY DROUGHT SUPPLY THROUGH THE DEVELOPMENT OF A SERIES OF WELLS IMMEDIATELY DOWNSTREAM FROM RECLAMATIONS TOM STEED RESERVOIR. THESE WELLS WILL PROVIDE SUPPLEMENTAL WATER TO THE CITIES OF ALTUS, FREDERICK, SNYDER, AND OTHERS AND PROVIDE SUPPLEMENTAL WATER TO ALTUS AIR FORCE BASE.THE DISTRICT PLANS THE INSTALLATION OF TWO WELLS TO AUGMENT THE WATER SUPPLY FROM TOM STEED RESERVOIR. THIS GROUNDWATER WILL TARGET 170-195 GALLONS PER MINUTE. THIS PROJECT WILL BRING THE FIRST GROUND WATER TO THIS REGION AND IN RETURN INCREASE DROUGHT RESILIENCY IN SW OKLAHOMA. THE PROPOSED PROJECT WILL SERVE TO AUGMENT THE CURRENT SUPPLY AS RECOMMENDED IN THE SOUTHWEST OKLAHOMA WATER SUPPLY ACTION PLAN.

NOVEL MYOFUNCTIONAL THERAPY WATER BOTTLE TO REDUCE OBSTRUCTIVE SLEEP APNEA AND SNORING - PROJECT SUMMARY: THERE IS A CLEAR UNMET NEED TO PROVIDE ALTERNATIVE, FIRST-LINE SOLUTIONS FOR BOTH OBSTRUCTIVE SLEEP APNEA (OSA) AND PRIMARY SNORING. MOST PEOPLE SUFFERING FROM OSA ARE CURRENTLY NOT RECEIVING TREATMENT WITH ESTIMATES OF 80% UNDIAGNOSED (23 MILLION AMERICANS) AND 40% NON-ADHERENCE TO THE GOLD STANDARD TREATMENT, CONTINUOUS POSITIVE AIR PRESSURE AMONG DIAGNOSED PATIENTS. THIS HAS SERIOUS IMPLICATIONS FOR OVERALL HEALTH RESULTING IN INCREASED DAYTIME SLEEPINESS AND COMORBIDITIES OF HYPERTENSION, HEART DISEASE, DIABETES, AND DEPRESSION. THE UNDIAGNOSED POPULATION ALONE CONTRIBUTES TO AN ESTIMATED COST BURDEN OF $30 BILLION FROM COMORBIDITIES AND MENTAL HEALTH, $26.2 BILLION FROM MOTOR VEHICLE ACCIDENTS, $6.5 BILLION FROM WORKPLACE ACCIDENTS, AND $86.9 BILLION FROM LOST PRODUCTIVITY, WITH A TOTAL COST BURDEN TO THE US OF $149.6 BILLION PER YEAR [1]. ALTHOUGH MOST PEOPLE ARE UNDIAGNOSED, INDICATORS SUCH AS SNORING CAN BE FOUND IN UP TO 94% OF OSA PATIENTS [2] AND HABITUAL SNORERS (SNORING = 3 NIGHTS/WEEK) WITH BED PARTNERS OFTEN SEEK TREATMENT FOR THEIR SNORING. LOW RISK, LOW BURDEN, AND AFFORDABLE SOLUTIONS THAT CAN BE EASILY ADMINISTERED TO OSA PATIENTS AND PRIMARY SNORERS OPEN NEW TREATMENT PARADIGMS TO REDUCE THE RISK OF OSA AND SNORING. OROPHARYNGEAL EXERCISES ARE A PROMISING THERAPY FOR MOTIVATED PATIENTS AND HAVE SHOWN, ON AVERAGE, TO REDUCE APNEA HYPOPNEA INDEX (AHI) BY 14.3 POINTS AND SNORING BY MORE THAN 50% [3,4]. DESPITE THEIR EFFICACY, A MAJOR OBSTACLE TO PATIENT ADOPTION AND ADHERENCE EXISTS THAT DEMANDS DELIVERY OF THERAPY IN LESS BURDENSOME WAYS. IN THIS SBIR PHASE I PROJECT, REMASTERED SLEEP WILL CHARACTERIZE, DEVELOP, AND CLINICALLY TEST A SIMPLIFIED MYOFUNCTIONAL THERAPY NOZZLE AND REUSABLE WATER BOTTLE TO IMPROVE ADOPTION AND ADHERENCE OF OROPHARYNGEAL EXERCISES. THE SIMPLIFIED EXERCISE REGIMEN AND CONNECTION OF THE THERAPY WITH THE BIOLOGICALLY DRIVEN ACTION OF DRINKING WATER GREATLY REDUCES DAILY THERAPY BURDEN, WHICH WILL LEAD TO IMPROVED PATIENT ADHERENCE AND ADOPTION. THE SPECIFIC AIMS ARE: AIM 1: CHARACTERIZE, DEVELOP, AND TEST PRE-PRODUCTION DEVICES. KEY THERAPY DESIGN FEATURES OF THE MYOFUNCTIONAL THERAPY NOZZLE WILL BE CHARACTERIZED. THE DEVICE WILL BE DEVELOPED AND TESTED TO WELL-DEFINED SPECIFICATIONS. THE PREPRODUCTION MODELS WILL USE PRODUCTION GRADE SILICONE MATERIALS TO MEET PRE-ESTABLISHED DESIGN AND SAFETY REQUIREMENTS. AIM 2: CONDUCT FEASIBILITY STUDY IN HUMAN SUBJECTS. A RANDOMIZED, NON-SIGNIFICANT RISK DEVICE STUDY WILL BE CONDUCTED TO ASSESS ADHERENCE AND QUALITY OF LIFE AFTER TWO MONTHS USE OF THE MT NOZZLE WATER BOTTLE VS. CONTROL FOR MILD TO MODERATE OSA PATIENTS. SECONDARY OUTCOME MEASURES WILL COMPARE CHANGES IN MYOFUNCTIONAL ASSESSMENT, AHI, OXYGEN SATURATION (SPO2), AND SNORING INTENSITY/PERCENTAGE. PHASE I WILL DE-RISK THE THERAPY AND DEVICE AND PROVIDE INPUT FOR A FUTURE PHASE II PROPOSAL THAT WILL FOCUS ON FURTHER OPTIMIZATION OF THE THERAPY AND CONDUCTING A LARGER MORE INCLUSIVE CLINICAL STUDY WITH EMPHASIS ON EFFICACY OF THE DEVICE IN TREATMENT OF SNORING AND MILD-MODERATE OSA. THIS PROPOSED WORK HAS THE POTENTIAL TO CREATE A NEW THERAPY PLATFORM FOR PATIENTS TO EASILY IMPROVE THEIR OSA AND SNORING.

TAS::57 3600::TAS 'SUPERSONIC CORNER FLOWS'

ADAPTABLE MECHANICAL METAMATERIALS WITH TAILORABLE TOUGHNESS AND ENERGY ABSORPTION

PROPOSAL FOR A DETERMINISTIC SOLID-STATE QUANTUM MEMORY

NICOP - NANOSTRUCTURED METAMATERIALS FOR HIGH-TC SUPERCONDUCTIVITY

TRADITIONAL; 18 MONTHS, FOREIGN ** FAADC MIGRATION NOTE - ACTION TYPE:"1" TO "A", ASSISTANCE TYPE:"4" TO "04", RECORD TYPE:"2", BUSINESS FUNDS INDICATOR:"NON", INDIVIDUAL RECIPIENT INDICATOR:"NO", RESEARCH AND DEVELOPMENT FUNDS INDICATOR:"YES", COMPETED OPPORTUNITY:"1" TO "C", NUMBER OF PROPOSALS OR APPLICATIONS:"1", AWARDING SUB-TIER AGENCY CODE "5700" DERIVED FROM AWARDING OFFICE CODE "FA9550", FUNDING SUB-TIER AGENCY CODE "5700" DERIVED FROM FUNDING OFFICE CODE "F3BB00", PPOP COUNTRY CODE:"GBR", PPOP FOREIGN LOCATION DESCRIPTION SET TO PPOP COUNTRY NAME "UNITED KINGDOM", SMALL BUSINESS INDICATOR:"O", SAM EXCEPTION:"X" **

AN ADVANCED, HIGH-THROUGHPUT IMAGING SYSTEM FOR THE BNI STRUCTURAL AND FUNCTIONAL IMAGING CORE - THIS APPLICATION IS A REQUEST FOR FUNDS TO ACQUIRE A ZEISS AXIOSCAN 7 SLIDE SCANNER FOR THE STRUCTURAL AND FUNCTIONAL IMAGING CORE AT THE BURKE NEUROLOGICAL INSTITUTE. THE INSTITUTE, DEDICATED TO FINDING CURES FOR CHRONIC NEUROLOGICAL DISABILITIES, REQUIRES AN AUTOMATED IMAGE ACQUISITION SYSTEM TO ADVANCE THEIR NIH-FUNDED RESEARCH. THE MANDATE OF THE IMAGING CORE FACILITY IS TO PROVIDE ACCESS TO A RANGE OF LIGHT MICROSCOPY SYSTEMS AND PROVIDE TECHNICAL ASSISTANCE WITH IMAGE ACQUISITION, PROCESSING, AND ANALYSIS TO ALL RESEARCH GROUPS WITHIN BNI. WHILE THE INSTITUTE HAS INVESTED IN HIGH-RESOLUTION CONFOCAL AND MULTIPHOTON MICROSCOPY SYSTEMS, IT LACKS MODERN EPIFLUORESCENCE AND BRIGHTFIELD IMAGING SYSTEMS. EXISTING MICROSCOPY SOLUTIONS ARE AGING AND LACK CRITICAL FEATURES FOUND IN THE PROPOSED AXIOSCAN 7 SYSTEM. THIS SCARCITY OF RESOURCES POSES A SIGNIFICANT BOTTLENECK FOR THE DIVERSE NIH-FUNDED RESEARCH PROGRAMS AT THE INSTITUTE. THE AXIOSCAN 7 SLIDE SCANNER, WITH ITS AUTOMATED FULL SLIDE WORKFLOW, UNLIMITED Z-STACK ACQUISITION PARAMETERS, AND ADVANCED DECONVOLUTION ALGORITHMS, OFFERS AN OPTIMAL COMBINATION OF FEATURES FOR LARGE AREA TISSUE SCANNING AND STITCHING. THE PROPOSED SYSTEM WILL GREATLY EXPEDITE RESEARCH PROGRESS BY REDUCING ACTIVE USER TIME DURING IMAGE ACQUISITION. FURTHERMORE, THE SURROUNDING AREA LACKS OTHER AUTOMATED, HIGH-THROUGHPUT MICROSCOPY RESOURCES ACCESSIBLE TO BNI INVESTIGATORS, MAKING THE AXIOSCAN 7 AN INDISPENSABLE ASSET. ITS IMPLEMENTATION WILL NOT ONLY BENEFIT CURRENTLY NIH-FUNDED RESEARCH PROGRAMS BUT ALSO CATALYZE THE PROGRESS OF STUDIES THAT ARE YET TO REACH THE MATURITY REQUIRED FOR NIH FUNDING. THE PROPOSED RESEARCH PROJECTS UNDERSCORE THE SHARED NEED FOR AN ADVANCED SLIDE SCANNING SYSTEM. IN CONCLUSION, THE EXTENSIVE CAPABILITIES AND EFFICIENT WORKFLOW OF THE AXIOSCAN 7 WILL EXERT A SUSTAINED, POWERFUL INFLUENCE ON THE CONDUCT OF NIH-FUNDED RESEARCH PROGRAMS AT THE BURKE NEUROLOGICAL INSTITUTE AND SUPPORT BREAKTHROUGHS IN THE UNDERSTANDING AND TREATMENT OF CHRONIC NEUROLOGICAL DISABILITIES.

INTRACORTICAL MYELIN AS A NOVEL NEURAL MARKER OF ALCOHOL USE DISORDER

MULTI-SCALE METHODS FOR DESIGN OF CREEP RESISTANT ALLOYS

BIO-INSPIRATION FOR EFFICIENT MOBILE SENSOR NETWORKS

DISSECTING MOTOR CORTEX MODULATION OF NOCICEPTION DURING CHRONIC PAIN - PROJECT SUMMARY (SEE INSTRUCTIONS): THE HEAVY BURDEN OF CHRONIC PAIN AND THE OPIOID EPIDEMIC HAS PROMPTED AN URGENT, WORLDWIDE SEARCH FOR ALTERNATIVE, NON-ADDICTIVE METHODS OF ANALGESIA. ONE PROMISING ALTERNATIVE IS NON-INVASIVE ELECTRICAL OR MAGNETIC STIMULATION OF THE MOTOR CORTEX (MC). WHILE MC STIMULATION (MCS) HAS REPEATEDLY BEEN FOUND TO REDUCE CHRONIC PAIN IN HUMAN SUBJECTS AND DECREASE NOCICEPTIVE BEHAVIORS IN RODENT MODELS, MAJOR QUESTIONS REMAIN ABOUT ITS MECHANISM OF ACTION AND HOW TO IMPROVE MCS EFFICACY. EVIDENCE SUGGESTS THAT MCS ANTINOCICEPTIVE EFFICACY INCREASES WHEN THE STIMULATION TARGETS THE REGION IN MOTOR CORTEX THAT CORRESPONDS TO THE BODY PART FROM WHICH PAIN ORIGINATES (SOMATOTOPICALLY MATCHING MCS) AND THAT MCS ANALGESIA REQUIRES ENDOGENOUS OPIOID ACTIVITY. HERE, I PROPOSE TO USE A RODENT MODEL OF TRIGEMINAL NEUROPATHIC PAIN TO ELUCIDATE THE UNDERLYING MECHANISM OF MCS ANTINOCICEPTION AND TO DEFINE KEY MCS FEATURES THAT PAIN CLINICIANS CAN USE TO IMPROVE MCS EFFICACY. TO CHARACTERIZE THE MCS MECHANISM, I WILL 1) QUANTIFY THE EFFICACY OF SOMATOTOPICALLY MATCHED MCS (SSMCS), 2) DETERMINE WHAT OPIOID RECEPTOR SUBTYPES ARE REQUIRED FOR MCS ANTINOCICEPTION, AND 3) IDENTIFY HOW ENDOGENOUS OPIOIDS MODULATE AN OPIOID-SENSITIVE MC DESCENDING CIRCUIT TO THE DESCENDING PAIN CONTROL PATHWAYS DURING SSMCS. TO DETERMINE THE EFFICACY OF MCS BETWEEN MATCHED AND OFF-TARGET MCS IN TWO DIFFERENT NERVE CONSTRICTION MODELS, I WILL USE CLASSIC BEHAVIORAL PARADIGMS ALONG WITH CUTTING-EDGE MACHINE LEARNING ALGORITHMS TO ANALYZE MOUSE BEHAVIORAL RESPONSES. I WILL THEN USE COMPLEMENTARY PHARMACOLOGICAL AND GENETIC MOUSE LINES TO DETERMINE HOW SSMCS IS IMPACTED BY DISTINCT OPIOID RECEPTOR TYPES. TO INTERROGATE THE COMBINED IMPACT OF MC SOMATOTOPY AND ENDOGENOUS OPIOID SIGNALING IN MCS ANALGESIA, I WILL FOCUS ON THE DESCENDING PROJECTION FROM MC TO DESCENDING PAIN CONTROL REGIONS, ROSTRAL VENTROMEDIAL MEDULLA (RVM) AND SPINAL TRIGEMINAL NUCLEUS CAUDALIS (SPVC). I WILL DETERMINE THE POSITIONS OF OPIOID RECEPTOR TYPES AND ENDOGENOUS OPIOID PEPTIDES ALONG THIS CIRCUIT AND THEN ASSESS THE IMPACT OF SSMCS WITH AND WITHOUT OPIOID SIGNALING ON NEURAL ACTIVITY IN MC, RVM, AND SPVC USING CUTTING-EDGE HIGH-DENSITY ELECTROPHYSIOLOGICAL TECHNIQUES. ALTOGETHER, THIS PROJECT WILL DETERMINE HOW MCS MODULATES NOCICEPTION THROUGH ENDOGENOUS OPIOID SIGNALING IN SOMATOTOPICALLY ALIGNED CIRCUITS. THE RESULTS WILL PROVIDE THE FIRST REPORT OF NEURAL ACTIVITY DURING AND AFTER SSMCS AT BOTH THE TARGET AND IN AN MC OUTPUT.

THE MECHANICAL CONTROL OF THE EMBRYONIC DEVELOPMENT OF THE CENTRAL NERVOUS SYSTEM

RESIDENT OPPORTUNITY AND SUPPORTIVE SERVICES - SERVICE COORDINATORS

PERFORM FUNDING SYS