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We describe the structure-guided optimization of the molecular fragments 2-amino-3-benzyloxypyridine 1 (IC50 1.3 mM) and 3-(2-(4-pyridyl)ethyl)indole 2 (IC50 35 μM) identified using X-ray crystallographic screening of p38α MAP kinase. Using two separate case studies, the article focuses on the key compounds synthesized, the structure−activity relationships and the binding mode observations made during this optimization process, resulting in two potent lead series that demonstrate significant increases in activity. We describe the process of compound elaboration either through the growing out from fragments into adjacent pockets or through the conjoining of overlapping fragments and demonstrate that we have exploited the mobile conserved activation loop, consisting in part of Asp168-Phe169-Gly170 (DFG), to generate significant improvements in potency and kinase selectivity.

Processing the vast amount of information required to provide quality nursing and health care today is an immense task. The Surgeon General of the Navy recently updated the Department's "Vision for the Future." He challenged Navy medicine to become a leader in technology integration. Shifting toward a managed-care environment makes it imperative for health care organizations and their personnel to integrate data, information, and systems at all levels. Implementation of a coordinator to assist nursing users with this technology is proving essential. This essay describes how one nursing directorate at a Naval hospital implemented a full-time staff member as Nursing Informatics Coordinator to serve in this role. Receiving and using data and information in the practice of nursing is vital to the profession. Specific factors identifying the reasons for development of this role, impact achieved, opportunities encountered, and the future of the position are addressed.

The effects of the hypothalamic 28 aminoacid peptide prosomatostatin (Pro-SS) on arginine-induced growth hormone (GH) and prolactin (PRL) release and blood glucose levels in man are compared with those obtained after an equimolar dose of somatostatin (SS). In comparison with SS, Pro-SS caused greater and more prolonged inhibition of GH release, a more marked reduction of the PRL response to arginine, and greater enhancement of the hyperglycaemic action of arginine. The greater potency and prolonged action of Pro-SS make it an interesting tool to study hormonal control mechanisms in a variety of physiological and pathological conditions.