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172,184 grants matching “inflammation”
Framingham Project/Levy
$2,785,722Daniel Levy · National Heart, Lung, And Blood Institute · ZIA · FY2014 · HL
Antecedents of Suicidal Behavior Related Neurobiology
$2,783,896Joseph J Mann · New York State Psychiatric Institute Dba Research Foundation For Mental Hygiene, Inc · P50 · FY2018 · MH
Cytokine signaling, immunoregulation and autoimmune disease
$2,782,678John O'Shea · National Institute Of Arthritis And Musculoskeletal And Skin Diseases · ZIA · FY2021 · AR
Molecular profiling and immunomodulatory interventions
$2,780,168Abraham Na Shaked · University Of Pennsylvania · U01 · FY2007 · AI
PACTTE-Partnership for Anemia: Clinical and Translational Trials in the Elderly
$2,779,958Harvey Jay Cohen · Duke University · U01 · FY2012 · AG
Expression, Structure/function And Regulation Of Phosphodiesterase 3 Isoforms
$2,779,790Vincent Manganiello · Heart, Lung, And Blood Institute · Z01 · FY2007 · HL
The Vascular Fibroblast: An Understudied Culprit In Postoperative Venous Stenosis
$2,777,206Laisel Martinez · University Of Miami School Of Medicine · R01 · FY2025 · DK
Inter-alpha Inhibitors in Hypoxic-Ischemic Brain Injury
$2,776,920Yow-Pin Lim · Prothera Biologics, Llc · R44 · FY2023 · NS
Selective actin remodeling of sensory neurons for acute pain management
$2,776,138Paul Blum · Neurocarrus, Inc. · R44 · FY2023 · NS
Aging-related hematopoietic stem cell intrinsic and microenvironmental signals in AML transformation
$2,775,137Stavroula Kousteni · Columbia University Health Sciences · P01 · FY2024 · CA
Protection of Ischemic Myocardium
$2,774,979Roberto Bolli · University Of Louisville · P01 · FY2017 · HL
Pathogenic Mechanisms in Spondyloarthritis
$2,774,828Robert Colbert · National Institute Of Arthritis And Musculoskeletal And Skin Diseases · ZIA · FY2019 · AR
DEFINITION PHASE ONLY. EVIDENCE HAS ACCUMULATED FROM ANIMAL STUDIES THAT THE CENTRAL NERVOUS SYSTEM UNDERGOES DELETERIOUS CHANGES AFTER EXPOSURE TO CHARGED PARTICLE RADIATION SUCH AS PROTONS AND HIGH ATOMIC NUMBER ATOMIC NUCLEI THAT ARE FOUND IN SPACE AS GALACTIC COSMIC RAYS AND SOLAR PARTICLE EVENTS. OBSERVED CHANGES INCLUDE INFLAMMATION OXIDATIVE STRESS LOSS OF NEURON (DENDRITE) BRANCHES AND CONNECTIONS (SYNAPSES) ALTERED SIGNALING MOLECULES ALTERED ELECTRICAL PROPERTIES LOSS OF BLOOD VESSELS AND IMPAIRED BEHAVIORAL PERFORMANCE. IF HUMANS RESPOND TO CHARGED PARTICLES IN THE SAME WAY AS ANIMALS THEN IT IS POSSIBLE THAT DELETERIOUS CHANGES MAY BE SUFFICIENT TO CAUSE COGNITIVE AND OTHER BEHAVIORAL IMPAIRMENTS THAT COULD COMPROMISE SPACEFLIGHT MISSIONS AND ASTRONAUT HEALTH. THE CURRENT EVIDENCE IS BASED PRIMARILY ON SHORT EXPOSURES TO SINGLE RADIATION TYPES. HOWEVER SPACE RADIATION IS A COMPLEX MIXTURE OF THESE PARTICLES AND EXPOSURES ACCUMULATE GRADUALLY OVER THE COURSE OF MISSIONS. IT IS WELL ESTABLISHED IN RADIATION BIOLOGY THAT REDUCTION OF THE DOSE RATE CAN HAVE A PROFOUND EFFECT ON THE OUTCOME. THEREFORE TO BETTER SIMULATE THE SPACE ENVIRONMENT WE PROPOSE TO EXPOSE ADULT MICE TO EITHER 0.5 GY PROTONS OR 0.25 AND 0.5 GY MIXTURES OF HELIUM OXYGEN AND SILICON PARTICLES IN 2:1:1 RATIOS AS THEY ARE FOUND IN SPACE. THEN WE WILL DELIVER THE EXPOSURES OVER LONG TIME PERIODS (UP TO 6 WEEKS) IN MULTIPLE SHORT EXPOSURES (FRACTIONS) COMPATIBLE WITH PARTICLE ACCELERATOR OPERATIONS. THESE RESULTS WOULD BE COMPARED TO RESULTS FROM ACUTE EXPOSURES TO ESTABLISH THE DOSE RATE EFFECTIVENESS FACTORS (DREFS) WHICH ARE NEEDED FOR RISK ESTIMATION FOR ASTRONAUT HEALTH. WE PREDICT THAT THE HIGH NUMBERS (FLUENCE) OF PROTONS WILL RESULT IN MULTIPLE TRAVERSALS OF CELLS WITHIN SHORT TIMES THAT MAY ELICIT INTERACTING BIOLOGICAL RESPONSES WHEREAS THE LOWER FLUENCE OF HIGHER CHARGED IONS WILL RESULT IN RARE INDEPENDENT EVENTS. DREFS>1 ARE PREDICTED FOR PROTONS AND DREFS ~1 ARE PREDICTED FOR HIGH Z PARTICLES. WE WILL ALSO COMPARE THE "PROTRACTED" EXPOSURES OF CHARGED PARTICLE MIXTURES TO GAMMA RAYS TO DETERMINE WHETHER THEY HAVE EQUIVALENT DOSE EFFECTS OR ARE MORE EFFECTIVE. THE RELATIVE BIOLOGICAL EFFECTIVENESS FACTOR (RBES) WILL BE DERIVED. THESE RBES ARE UTILIZED IN PREDICTING DENSELY IONIZING RADIATION EFFECTS IN HUMANS FOR WHOM ONLY GAMMA RAY AND X-RAY DATA ARE AVAILABLE WITH THE ASSUMPTION THAT THE RATIOS OBTAINED IN ANIMAL MODELS ARE REALISTIC SURROGATES FOR HUMANS. WE WILL TEST BOTH MALE AND FEMALE ANIMALS AS THEIR RESPONSES ARE NOT IDENTICAL AND THE ASTRONAUT POPULATION IS OF MIXED GENDER. FOR EACH OF THE EXPOSURE REGIMENS WE WILL CONDUCT A BATTERY OF BEHAVIOR TESTS MEASURE ELECTROPHYSIOLOGICAL PROPERTIES IN TISSUE SLICES AND QUANTIFY CHANGES IN THE STRUCTURE AND COMPOSITION OF THE TISSUE USING STATE OF THE ART BIOCHEMICAL HISTOCHEMICAL AND MICROSCOPY METHODS. THIS WILL ALLOW US TO IDENTIFY THE UNDERLYING PHYSIOLOGICAL CHANGES MOST SENSITIVE TO DOSE RATE AND RADIATION QUALITY AND HOW THEY COMBINE TO PRODUCE BEHAVIORS THAT ARE ADAPTIVE OR MALADAPTIVE. TOGETHER THE DATA GENERATED BY THE PROJECT WILL ENHANCE NASAS ABILITY TO TRANSLATE ANIMAL ASSESSMENTS OF CNS STRUCTURE AND FUNCTION TO HUMANS AND TO UPDATE RISK ESTIMATES BASED ON SINGLE RADIATION SPECIES HIGH DOSE RATE IRRADIATION PROTOCOLS TO HIGHER FIDELITY SPACE-LIKE EXPOSURES OF CHARGED PARTICLE MIXTURES DELIVERED AT DOSE RATES APPROACHING THOSE OBSERVED IN SPACE.
$2,773,956Loma Linda University · · FY2020 · National Aeronautics and Space Administration
Pathogenesis, and Outcome of Autoinflammatory Diseases, NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still's-like Diseases, and other Undifferentiated Autoinflammatory Diseases
$2,773,603Raphaela Goldbach-Mansky · National Institute Of Allergy And Infectious Diseases · ZIA · FY2020 · AI
MIND Diet Intervention to Prevent Alzheimer's Disease
$2,773,089Martha C. Morris · Rush University Medical Center · R01 · FY2016 · AG
Pharmacogenomics of Arrhythmia Therapy
$2,772,165Dan M Roden · Vanderbilt University · U01 · FY2009 · HL
Clinical trial of omalizumab for allergen sensitized and exposed individuals with COPD
$2,771,146Nirupama Putcha · Johns Hopkins University · U01 · FY2025 · AI
UC Davis CounterACT Center of Excellence: Developing Therapeutic Strategies for Mitigating the Chronic Neurological Consequences of Acute Organophosphate Intoxication
$2,770,046Pamela J Lein · University Of California At Davis · U54 · FY2024 · NS
Systems Immunogenetics of Biodefense and Emerging Pathogens in the Collaborative Cross
$2,769,729Ralph S Baric · Univ Of North Carolina Chapel Hill · U19 · FY2019 · AI
Clarifying the Optimal Application of SLT Therapy (COAST) Trial
$2,769,231Stephen R Wisniewski · University Of Pittsburgh At Pittsburgh · UG1 · FY2023 · EY
Molecular Analysis Of Leukocyte Activation By Chemoattractants
$2,765,551Philip Murphy · National Institute Of Allergy And Infectious Diseases · ZIA · FY2010 · AI
Pediatric Eye Disease Investigator Group Coordinating Center
$2,763,504Raymond Kraker · Jaeb Center For Health Research, Inc. · U10 · FY2014 · EY
UC Davis CounterACT Center of Excellence: Developing Therapeutic Strategies for Mitigating the Chronic Neurological Consequences of Acute Organophosphate Intoxication
$2,762,691Pamela J Lein · University Of California At Davis · U54 · FY2025 · NS
Development Of New Approaches To Vaccines Against TBEV and West Nile Virus
$2,761,944Alexander Pletnev · Niaid Extramural Activities · Z01 · FY2007 · AI
Systemic Autoimmunity
$2,759,908Mariana Kaplan · National Institute Of Arthritis And Musculoskeletal And Skin Diseases · ZIA · FY2016 · AR