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Project Summary Crystallization followed by subsequent structure determination is a major step in understanding the structure function relationship of macromolecules Understanding macromolecule structure has become a key part in the development of new pharmaceuticals and is a major area of NIH research Crystallization however is also the rate limiting step despite technological efforts to a ...

Abstract During Phase Iwe will test the feasibility of developing a magnetographic camera technology as a new tool in neuroscience to facilitate the detailed analysis of electrical currents in diverse neuronal circuitsInstead of photographic imagesthe camera will produce single shot images of the magnetic fields from in vivo samples of interestsuch as a patch of the grey matter in the cerebral cor ...

DESCRIPTION provided by applicant There is an unmet need to inhibit the key cancer promoting transcription factor MYC MYC both cMYC and MYCN acts downstream of many cell receptor complexes and signal transduction pathways to activate genes that drive cancer cell growth and proliferation To date small molecule inhibitors of MYC have been elusive An innovative approach would be to indirectl ...

PARP inhibitors PARPi are particularly efficacious in tumors deficient in the BRCA tumor suppressor genes but of limited activity in BRCA competent tumors There is an unmet medical need to develop targeted therapeutic agents which will augment PARPi activity for BRCA wild type cancers and to increase chemo radiosensitivity in these malignancies BRCA proteins are essential components ...

Project SummaryAbstract Tumor imaging quantification is critical for diagnosisstagingand treatment evaluationand multi detector CTMDCTis the clinical imaging modality commonly used for patients diagnosed with hepatic malignancy because of its relatively low cost and wide availabilityConventional tumor quantification using either linear or volumetric measurement has demonstrated significant limitat ...

DESCRIPTION provided by applicant There is a significant need for novel HIV therapies given the emergence of viruses resistant to existing drug regimens The Rev RRE protein RNA interaction in HIV plays an essential role in the transport of viral mRNA from the nucleus to the cytoplasm where it can be translated or packaged Previously we identified the thienopyridine scaffold that inhibited HIV ...

Project SummaryNuclear magnetic resonanceNMRis amongst the most powerful analytical techniques ever inventedas recognized byNobel Prizes for methods development aloneNonethelessNMR is notoriously plagued by poor sensitivity and spatial resolutionState of the art NMR spectrometers typically feature detection thresholds ofnanograms forL sample volumesThis places NMR sensitivity many orders of magnit ...

ABSTRACT Acute kidney injuryAKIis a syndrome characterized by rapid loss of the kidneyandapos s excretory functionAKI is the leading cause of nephrology consultation and results inmillion hospital admissions a yearThe socioeconomic impact of AKI is significantresulting in $billion cost to the health care systemDespite the high rate of incidence of AKIno therapy currently existsother than supportiv ...

DESCRIPTION provided by applicant Insulin resistance IR also known as metabolic syndrome is tied to obesity and is associated with numerous modern health problems including the growing problems of type diabetes and cardiovascular disease The growing health economic and social burdens of these conditions calls for the need to develop drug treatments for IR We know from multiple lines of ...

DESCRIPTION provided by applicant African American men experience health disparities across a number of preventable chronic diseases including cardiovascular disease strokes obesity and diabetes Physical activity PA is a modifiable risk factor for these conditions The few PA promotion studies that have included African American men have resulted in successful short term behavior change ...