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Juvenile hormones (JHs) play a major role in controlling development and reproduction in insects and other arthropods. Synthetic JH-mimicking compounds such as methoprene are employed as potent insecticides against significant agricultural, household and disease vector pests. However, a receptor mediating effects of JH and its insecticidal mimics has long(More)
We show that 85% of variation in total organic carbon can be explained by mineral surface area in a black shale deposit from two locations in the late Cretaceous Western Interior Seaway, United States. This relation suggests that, as in modern marine sediments, adsorption of carbon compounds onto clay mineral surfaces played a fundamental role in the burial(More)
Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the(More)
Compound-specific analyses of the 34 S/ 32 S isotope ratios of individual organosulfur compounds in Upper Jurassic oil and condensate samples from the Smackover Fm. reveal differences of up to $50& between compounds. There is a clear distinction between oils altered by thermochemical sulfate reduction (TSR) versus those that are not. Oils that did(More)
Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to(More)
In T cells, the Tec kinases IL-2-inducible T cell kinase (ITK) and resting lymphocyte kinase (RLK) are activated by TCR stimulation and are required for optimal downstream signaling. Studies of CD4(+) T cells from Itk(-/-) and Itk(-/-)Rlk(-/-) mice have indicated differential roles of ITK and RLK in Th1, Th2, and Th17 differentiation and cytokine(More)
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