The effects of the Cl channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), 1,9-dideoxyforskolin (DDF), dipyridamole, and niflumic acid and of the polyunsaturated fatty acids arachidonic, linolenic, and linoleic acids on regulatory volume decrease (RVD) and associated 125I and [3H]taurine fluxes in cultured rat cerebellar granule neurons were examined. Dose-response curves of NPPB, DDF, and dipyridamole showed 20-100% inhibition of RVD and osmolyte fluxes. Niflumic acid was less potent, requiring 150-600 microM to show effects of this magnitude. The polyunsaturated fatty acids (5-20 microM) inhibited 80-90% RVD and osmolyte fluxes, with arachidonic acid exhibiting the most potent effect. The volume-associated taurine efflux was somewhat higher in younger neurons, but the pharmacological sensitivity was essentially the same in immature and mature cells. The effects of all tested drugs on 125I and [3H]taurine fluxes were remarkably similar, indicating a close pharmacological sensitivity of the transport mechanism for the two osmolytes. This is in line with the suggestion of a common pathway for the volume-associated release of Cl and amino acids functioning as osmolytes.
El riesgo de crédito es una de las principales preocupaciones de los organismos de supervisión y regulación financiera, así como de las instituciones bancarias. Así, se propone un modelo de puntuación crediticia basado en una regresión logística, para analizar la probabilidad de incumplimiento por segmentos de una cartera de clientes de tarjeta de crédito de una institución mexicana. Los resultados muestran que el modelo propuesto tiene un alto nivel de predictibilidad y de estabilidad, tanto fuera como dentro del periodo de modelado, la comprobación de monotonicidad, también asegura que el modelo tenga un alto nivel de precisión. La originalidad subyace en que existen escasos estudios sobre modelos de puntuación crediticia para México, el resultado del modelo tiene alto nivel de precisión y arroja como resultado una tabla de puntuación de fácil interpretación para el personal bancario. Se concluye que el modelo es confiable y con alto nivel de ajuste.
Small peptide aldehydes (SPAs) with protease inhibitory activity are natural products typically synthesized by nonribosomal peptide synthetases (NRPS). SPAs are widely used in biotechnology, as therapeutic agents, they are physiologically relevant and regulate development of the natural hosts. During genome evolutionary analysis of Streptomyces lividans 66 we identified an NRPS-like biosynthetic gene cluster (BGC) that lacked a condensation (C) domain but included a tRNA-Utilizing Enzyme (tRUE) belonging to the leucyl/phenylalanyl (L/F) transferase family. This system was predicted to direct the synthesis of a novel SPA with protease inhibitory activity, called livipeptin. Following genome mining and phylogenomic analyses we confirmed the presence of tRUEs within diverse Streptomyces genomes, including fusions with a C-minus NRPS-like protein. We further demonstrate functional cooperation between these enzymes and provide the biosynthetic rules for the synthesis of livipeptin, expanding the known universe of acetyl-leu/phe-arginal SPAs. The L/F-transferase C-minus NRPS productive interaction was shown to be tRNA-dependent after semisynthetic assays in the presence of RNAse, which contrasts with leupeptin, an acetyl-leu-arginal SPA that we show to be produced by Streptomyces roseous ATCC 31245 via a tRUE-minus BGC with multiple complete NRPSs. Thus, livipeptin and leupeptin are the result of convergent evolution, which has driven the appearance of unprecedented biosynthetic logics directing the synthesis of protease inhibitors thought to be at the core of Streptomyces colony biology. Our results pave the way for understanding this Streptomyces trait, as well as for the discovery of novel natural products following evolutionary genome mining approaches.
The determination of distances is highly constrained to a small number of Gamma-Ray Bursts (GRBs) because it requires observations at different wavelengths. Some empirical functions to estimate redshifts have been identified using populations of GRBs with reported redshifts. For example, the Amati correlation relates E peak of the spectrum when modeled with a Band function and the total energy emitted E iso in a time integrated analysis. A multiple-component scenario has been proposed in order to explain GRBs spectra, and in this context when a fine-time spectral analysis is performed a correlation between the non-thermal component's peak energy and the luminosity (E peak,i − L i) appears. This correlation is also used to infer distances to GRBs. In this work we present a sample of bright GRBs and apply these empirical correlations to constrain the pseudo-redshift of the selected burst sample. Our results for GRB080916C, GRB090926A and GRB150214A with reported redshift are totally consistent. Another three bursts with lower luminosities were selected. For these bursts, the pseudo-redshift range obtained with the two correlations are not totally in agreement.
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