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UNLABELLED The accuracy of current signal peptide predictors is outstanding. The most successful predictors are based on neural networks and hidden Markov models, reaching a sensitivity of 99% and an accuracy of 95%. Here, we demonstrate that the popular BLASTP alignment tool can be tuned for signal peptide prediction reaching the same high level of(More)
SUMMARY The performance of sequence database search methods is usually judged by receiver operating characteristic (ROC) analysis. The proper interpretation of the results obtained and a fair comparison across different methods critically depends on the properties of the data set used for such an analysis; in particular, each query must have the same number(More)
This analysis was conducted to determine whether the hepatitis C virus (HCV) viral kinetics (VK) model can predict viral load (VL) decreases for nonnucleoside polymerase inhibitors (NNPolIs) and protease inhibitors (PIs) after 3-day monotherapy studies of patients infected with genotype 1 chronic HCV. This analysis includes data for 8 NNPolIs and 14 PIs,(More)
The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity(More)
Gene expression was evaluated in the myocardium of male Wistar rats after a single subcutaneous administration of 0.5 mg of isoproterenol, a beta-adrenergic agonist that causes acute tachycardia with subsequent myocardial necrosis. Histology of the heart, clinical chemistry, and hematology were evaluated at 9 time points (0.5 hours to 14 days(More)
Multiprotein complexes govern virtually all cellular processes. Their 3D structures provide important clues to their biological roles, especially through structural correlations among protein molecules and complexes. The detection of such correlations generally requires comprehensive searches in databases of known protein structures by means of appropriate(More)
Model Driven Architecture (MDA) is a technology that has been in the process of evolution for many years. We looked at this technology last year in a panel that raised the roof. Today, more vendors are now producing products that support MDA. And we still hear about the success stories that indicate that this technology is the "real deal". But, with the(More)
R411 is a dual antagonist of α4β1–α4β7 integrins that targets the inflammatory process in respiratory airways. It has shown good efficacy in animal disease models [1] and is currently under development for the treatment of chronic asthma. Following oral administration, R411 is rapidly and completely biotransformed into its active metabolite, RO0270608,(More)
From a series of N-acyl 4-(3-pyridonyl)phenylalanine derivatives of 4, the trifluoromethyl derivative 28 was identified as a potent, dual acting alpha4 integrin antagonist with activity in primate models of allergic asthma. Investigation of a series of prodrug esters led to the discovery of the morpholinopropyl derivative 48 that demonstrated good(More)