Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2(nd) generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

Cartas enviadas por José Antonio Arana Martija a Justo Garate entre 1985 y 1993

9 cartas (mecanografiadas) ; 207x300mm. Ubicación: Caja 1 - Carpeta 36

Carta enviada por José Ignacio de Arana a Justo Garate en 1940

1 carta (manuscrita) ; 270x180mm. Ubicación: Caja 1 - Carpeta 37

Carta enviada por José de Ariztimuño a Justo Garate en 1933

1 carta (mecanografiada) ; 215x135mm. Ubicación: Caja 1 - Carpeta 51

Carta enviada por José de Arriga a Justo Garate en 1947

1 carta (mecanografiada) ; 340x165mm. Ubicación: Caja 1 - Carpeta 61

Cartas enviadas por José de Arteche a Justo Garate entre 1952 y 1960

10 cartas (mecanografiadas y manuscritas) ; entre 210x230mm y 230x170mm. Ubicación: Caja 1 - Carpeta 66

Cartas enviadas por José de Arteche a Justo Garate entre 1961 y 1971

10 cartas (mecanografiadas y manuscritas) ; entre 210x230mm y 155x215mm. Ubicación: Caja 1 - Carpeta 66

Cartas enviadas por José Angel Ascunde a Justo Garate entre 1991 y 1994

9 cartas y 1 tarjeta de visita (mecanografiadas y manuscritas) ; 210x295mm. Ubicación: Caja 1 - Carpeta 70

História e costumes

Inclui uma ilustração assinada por Simão de Vasconcellos (José de Anchieta), e outras anônimas: Largo do Passo no tempo do Conde de Resende, Leilão de escravos, O filósofo do Cáes (figura mitológica), retrato de Manuel de araújo Porto Alegre, de Dom Pedro II (criança) e outra com as princesas irmãs, e do Visconde de São Leopoldo

Mateda-2.0: Estimation of Distribution Algorithms in MATLAB

This paper describes Mateda-2.0, a MATLAB package for estimation of distribution algorithms (EDAs). This package can be used to solve single and multi-objective discrete and continuous optimization problems using EDAs based on undirected and directed probabilistic graphical models. The implementation contains several methods commonly employed by EDAs. It is also conceived as an open package to allow users to incorporate different combinations of selection, learning, sampling, and local search procedures. Additionally, it includes methods to extract, process and visualize the structures learned by the probabilistic models. This way, it can unveil previously unknown information about the optimization problem domain. Mateda-2.0 also incorporates a module for creating and validating function models based on the probabilistic models learned by EDAs.

Prioritization of candidate cancer genes-an aid to oncogenomic studies

The development of techniques for oncogenomic analyses such as array comparative genomic hybridization, messenger RNA expression arrays and mutational screens have come to the fore in modern cancer research. Studies utilizing these techniques are able to highlight panels of genes that are altered in cancer. However, these candidate cancer genes must then be scrutinized to reveal whether they contribute to oncogenesis or are coincidental and non-causative. We present a computational method for the prioritization of candidate (i) proto-oncogenes and (ii) tumour suppressor genes from oncogenomic experiments. We constructed computational classifiers using different combinations of sequence and functional data including sequence conservation, protein domains and interactions, and regulatory data. We found that these classifiers are able to distinguish between known cancer genes and other human genes. Furthermore, the classifiers also discriminate candidate cancer genes from a recent mutational screen from other human genes. We provide a web-based facility through which cancer biologists may access our results and we propose computational cancer gene classification as a useful method of prioritizing candidate cancer genes identified in oncogenomic studies.

Phosphorylation of the carboxy-terminal domain of histone H1: effects on secondary structure and DNA condensation

Linker histone H1 plays an important role in chromatin folding. Phosphorylation by cyclin-dependent kinases is the main post-translational modification of histone H1. We studied the effects of phosphorylation on the secondary structure of the DNA-bound H1 carboxy-terminal domain (CTD), which contains most of the phosphorylation sites of the molecule. The effects of phosphorylation on the secondary structure of the DNA-bound CTD were site-specific and depended on the number of phosphate groups. Full phosphorylation significantly increased the proportion of -structure and decreased that of -helix. Partial phosphorylation increased the amount of undefined structure and decreased that of -helix without a significant increase in -structure. Phosphorylation had a moderate effect on the affinity of the CTD for the DNA, which was proportional to the number of phosphate groups. Partial phosphorylation drastically reduced the aggregation of DNA fragments by the CTD, but full phosphorylation restored to a large extent the aggregation capacity of the unphosphorylated domain. These results support the involvement of H1 hyperphosphorylation in metaphase chromatin condensation and of H1 partial phosphorylation in interphase chromatin relaxation. More generally, our results suggest that the effects of phosphorylation are mediated by specific structural changes and are not simply a consequence of the net charge.

Cartas enviadas por José Atin a Justo Garate entre 1982 y 1986

5 cartas y 1 tarjeta de visita (mecanografiadas y manuscritas) ; entre 215x275mm y 172x222mm. Ubicación: Caja 1 - Carpeta 74

Cartas enviadas por José Miguel de Azaola a Justo Garate entre 1968 y 1977

3 cartas, 1 Tarjeta de Navidad y 1 Tarjeta de Visita (mecanografiadas y manuscritas) ; entre 215x275mm y 160x108mm. Ubicación: Caja 1 - Carpeta 80