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Recent FDA approvals of ipilimumabnivolumaband pembrolizumabwhich target checkpoint receptors cytotoxic T lymphocyte associated antigenCTLAand programmed deathPDhave ushered in a new era of cancer immunotherapy in metastatic melanomaDespite unprecedented overall survival benefits with combination therapythe incidence of complete responses are onlyimmune related adverse eventsirAEsare increasedand ...

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 ...

Project Summary Metabolic reprogramming plays a critical role in carcinogenesisin part due its ability to promote immune suppressive properties within tumorsHoweverit is unclear whether inhibition of fatty acid metabolism in tumors affects their immunogenicityHerewe show for the first time that inhibition of stearoyl CoA desaturaseSCDthe rate limiting enzyme involved in fatty acid synthesis conver ...

PROJECT SUMMARY Developing an Automated Yeast Dissection System for Aging ResearchAging is the single greatest risk factor for diseases that are principal causes of mortalityThe objectives of aging research are to discover key genes and pathways related to aging that may eventually contribute to retardation of aging and a delay in the onset of age associated diseasesThe budding yeast Saccharomyces ...

We will develop a lab-on-chip optical absorption spectrometer spanning 3-15micron molecular fingerprint region, in a single epitaxially grown heterostructure that monolithically integrates thermally tuned distributed feedback quantum cascade laser (QCL) and quantum cascade detector (QCD) arrays with slotted photonic crystal waveguides (SPCWs) in a mid-infrared InGaAs passive photonic waveguide. In ...

A multichannel GPS system, with associated Controlled Radiation Pattern Antenna Array (CRPA) design, will provide continuous position and attitude determination. This system supports L1/L2 and SAASM or M-Code modes under both GPS jamming, and spoofing attack, to maintain navigation and attitude in contested environments. The system uses direction finding to determine angle of arrival (AOA for the ...

Different regions of the human GI tract exhibit different chemical environments and different digestion metabolites. As a result, these regions support different microorganisms, with gradients in metabolic products along the length of the GI tract. Single-point measurements of microbiome metabolites (e.g. in feces) are insufficient to provide detailed information of physiological status because th ...

Americas current electronic warfare (EW) capabilities are insufficient for the modern and future battlefield. To safeguard against radio-controlled threats and disrupt enemy communications, our current EW systems blindly jam broad swaths of the electromagnetic spectrum (EMS). This approach interferes with Blue Force data and voice communications, requires large power sources and generates distinct ...

The primary objective of this Phase II proposal is to construct and validate the portable SpectralMD DeepView imaging technology designed previously in Phase I. This device allows surgeons to quickly and objectively assess tissue viability in burn surgery prior to skin grafting. DeepView uses machine learning and multispectral imaging to generate quantitative prognostic images with easily interpre ...

Explosions and high-velocity impacts can create strain rates on the order of 105 to 107 s-1.To simulate these events, first-principles codes require material models that are valid at these loading rates.Currently, the amount of test data, material models and material constants for this strain rate range is extremely limited, and an innovative and cost-effective laboratory test procedure is needed. ...