Grid warehousing of molecular dynamics protein unfolding data

With the increasing awareness of protein folding disorders, the explosion of genomic information, and the need for efficient ways to predict protein structure, protein folding and unfolding has become a central issue in molecular sciences research. Molecular dynamics computer simulations are increasingly employed to understand the folding and unfolding of proteins. Running protein unfolding simulations is computationally expensive and finding ways to enhance performance is a grid issue on its own. However, more and more groups run such simulations and generate a myriad of data, which raises new challenges in managing and analyzing these data. Because the vast range of proteins researchers want to study and simulate, the computational effort needed to generate data, the large data volumes involved, and the different types of analyses scientists need to perform, it is desirable to provide a public repository allowing researchers to pool and share protein unfolding data. This paper describes efforts to provide a grid-enabled data warehouse for protein unfolding data. We outline the challenge and present first results in the design and implementation of the data warehouse

Structural characterization of the minimal segment of TDP-43 competent for aggregation

TDP-43 is a nuclear protein whose abnormal aggregates are implicated in ALS and FTLD. Recently, an Asn/Gln rich C-terminal segment of TDP-43 has been shown to produce aggregation in vitro and reproduce most of the protein's pathological hallmarks in cells, but little is known about this segment's structure. Here, CD and 2D heteronuclear NMR spectroscopies provide evidence that peptides corresponding to the wild type and mutated sequences of this segment adopt chiefly disordered conformations that, in the case of the wild type sequence, spontaneously forms a β-sheet rich oligomer. Moreover, MD simulation provides evidence for a structure consisting of two β-strands and a well-defined, yet non-canonical structural element. Furthermore, MD simulations of four pathological mutations (Q343R, N345K, G348V and N352S) occurring in this segment predict that all of them could affect this region's structure. In particular, the Q343R variant tends to stabilize disordered conformers, N345K permits the formation of longer, more stable β-strands, and G348V tends to shorten and destabilize them. Finally, N352S acts to alter the β-stand register and when S352 is phosphorylated, it induces partial unfolding. Our results provide a better understanding of TDP-43 aggregation process and will be useful to design effectors capable to modulate its progression. © 2014 Elsevier Inc. All rights reserved.Peer Reviewe

Privatizar ou não? Eis a questão: um estudo empírico sobre a rentabilidade das empresas de economia mista e empresas privadas listadas na Bovespa no período de 1995 a 2007

O objetivo deste trabalho foi verificar se a rentabilidade das empresas de economia mista é diferente da rentabilidade das empresas privadas, levando-se em consideração o tamanho das empresas e o custo da dívida. Foram analisadas as empresas listadas na Bovespa, compreendendo o período de 1995 a 2007. Os dados foram coletados no software Economática. Assim, procurou-se responder à seguinte questão: as empresas brasileiras de economia mista têm desempenho similar ao das empresas privadas? Para o teste da hipótese empregou-se regressão com dados em painel utilizado como proxy: para a rentabilidade, o Lair (lucro antes do imposto de renda); para o tamanho, o log de ativo; e, para o custo de captação de recursos, o custo da dívida (Kd). No que se refere à diferenciação de rentabilidade entre empresas de economia mista e empresas de economia privada, os resultados encontrados corroboram os achados de estudos anteriores. Observou-se neste estudo que tanto o tamanho quanto o custo da dívida estão relacionados à rentabilidade das empresas, mas o fato de a empresa brasileira ser de economia mista ou privada não interfere em sua rentabilidade