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Project Summary Abstract Multiple MyelomaMMis the second most common form of blood cancer and remains an incurable and deadly diseaseProteasome inhibitorPItherapy is a cornerstone in the treatment of MMbut resistance to this class of agent is an emerging challenge in the clinicNew therapeutic approaches that specifically target resistance are needed to maximize responses and ultimately produce cur ...

The goal of this workis to establish a radiation-aware capability in a commercial EDA design flow that will enable first-pass success in radiation resiliency for DoD ASIC designs in much the same way that existing EDA design suites ensure first pass functionality and performance success of complex ASICs destined for commercial applications.Such an integrated capability does not presently exist.The ...

Autism spectrum disorderASDis a neurodevelopmental disorder characterized by significant deficits in reciprocal social interactionsimpaired communication and restrictedrepetitive behaviorswith a prevalence ofinchildren in the USEarly intervention programs have been shown to be effective for improving IQlanguageand social skills for toddlers as young asmonths of ageDiagnosis of ASD is currently bas ...

PROJECT SUMMARY: COVID-19 is significantly more lethal in the elderly1 with the greatest risk in those cared for in long-term care facilities (LTCs) where mortality rates range from 19% to 72% worldwide. Monitoring COVID-19 infections in LTCs remains a particular challenging. The existing and a continued expected shortage of sufficient molecular COVID-19 testing coupled to false negative rates as ...

PROJECT SUMMARYAminoglycosides are one of the cheapest and well known antibiotics in clinical use for overyearsbut one of the major limitations in their use is their ototoxicityWe are developing fast and low cost methods to develop aminoglycosides with antiribosomal activities and reduced toxicityIn this projectwe will identify novel aminoglycoside antibacterialsthat show reduced ototoxicityComple ...

Project Summary While nucleic acid therapeutics have shown promise in rodent and nonhuman primate models of CNS diseasesall double blind clinical trials to date have failedOne likely explanation for this failure is poor therapeutic distribution in targeted brain regionsFor examplepost mortem studies of patients with Parkinsonandapos s Disease receiving intraparenchymal injections of AAV NTN demons ...

PROJECT SUMMARY Enzyme by DesignIncEbDis developing a safer version of L asparaginase that can be used routinely in the treatment of adult ALL patients whose hypersensitivity to todayandapos s bacterial L asparaginases deprives them from this efficacious therapyEbDandapos s L asparaginase is novel due to its mammalianguinea pigorigin and its lack of L glutaminase co activityThe need for better the ...

PROJECT SUMMARYfluorouracilFUhas been the first choice chemotherapy drug for colorectal cancerCRCfor many yearshoweverits clinical utility remains hindered by hematopoietic and gastrointestinal toxicities resulting from its non selectivitySide effects include fatigueloss of appetiteand diarrhea among othersall of which can lead to reduced quality of lifeThe economic burden associated with chemothe ...

Project Summary Abstract Kidney stonesKSare highly prevalentexcruciatingand associated with long term complications of chronic kidney diseaseCKDand end stage renal diseaseESRDThey account forM ER visits and andgt $B of medical costs annually and have a striking recurrence rate ofinyears and up toinyearsreflecting the inadequacies of current interventionsof KS are composed of calcium oxalate and sm ...

PROJECT SUMMARY There is a clear unmet need for effective treatments for acute myeloid leukemiaAMLAn exciting new mechanism for targeting cancer cells involves the activation of the extrinsic apoptotic pathway by administering the soluble domain of TNF related apoptosis inducing ligandTRAILcalled dulanerminMuch hope has been placed on this drug since TRAIL has been shown to bind to death receptors ...