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Understanding the biological activity profile of the snake venom components is fundamental for improving the treatment of snakebite envenomings and may also contribute for the development of new potential therapeutic agents. In this work, we tested the effects of BthTX-I, a Lys49 PLA2 homologue from the Bothrops jararacussu snake venom. While this toxin induces conspicuous myonecrosis by a catalytically independent mechanism, a series of in vitro studies support the hypothesis that BthTX-I might also exert a neuromuscular blocking activity due to its ability to alter the integrity of muscle cell membranes. To gain insight into the mechanisms of this inhibitory neuromuscular effect, for the first time, the influence of BthTX-I on nerve-evoked ACh release was directly quantified by radiochemical and real-time video-microscopy methods. Our results show that the neuromuscular blockade produced by in vitro exposure to BthTX-I (1 μM) results from the summation of both pre- and postsynaptic effects. Modifications affecting the presynaptic apparatus were revealed by the significant reduction of nerve-evoked [3H]-ACh release; real-time measurements of transmitter exocytosis using the FM4-64 fluorescent dye fully supported radiochemical data. The postsynaptic effect of BthTX-I was characterized by typical histological alterations in the architecture of skeletal muscle fibers, increase in the outflow of the intracellular lactate dehydrogenase enzyme and progressive depolarization of the muscle resting membrane potential. In conclusion, these findings suggest that the neuromuscular blockade produced by BthTX-I results from transient depolarization of skeletal muscle fibers, consequent to its general membrane-destabilizing effect, and subsequent decrease of evoked ACh release from motor nerve terminals. © 2012 Elsevier Ltd.

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Following the thermodynamic formulation of a multifractal measure that was shown to enable the detection of large fluctuations at an early stage, here we propose a new index which permits us to distinguish events like financial crises in real time. We calculate the partition function from which we can obtain thermodynamic quantities analogous to the free energy and specific heat. The index is defined as the normalized energy variation and it can be used to study the behavior of stochastic time series, such as financial market daily data. Famous financial market crashes-Black Thursday (1929), Black Monday (1987) and the subprime crisis (2008)-are identified with clear and robust results. The method is also applied to the market fluctuations of 2011. From these results it appears as if the apparent crisis of 2011 is of a different nature to the other three. We also show that the analysis has forecasting capabilities. © 2012 Elsevier B.V. All rights reserved.

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An algorithm for real-time and onboard orbit determination applying the Extended Kalman Filter (EKF) method is developed. Aiming at a very simple and still fairly accurate orbit determination, an analysis is performed to ascertain an adequacy of modeling complexity versus accuracy. The minimum set of to-be-estimated states to reach the level of accuracy of tens of meters is found to have at least the position, velocity, and user clock offset components. The dynamical model is assessed through several tests, covering force model, numerical integration scheme and step size, and simplified variational equations. The measurement model includes only relevant effects to the order of meters. The EKF method is chosen to be the simplest real-time estimation algorithm with adequate tuning of its parameters. In the developed procedure, the obtained position and velocity errors along a day vary from 15 to 20 m and from 0.014 to 0.018 m/s, respectively, with standard deviation from 6 to 10 m and from 0.006 to 0.008 m/s, respectively, with the SA either on or off. The results, as well as analysis of the final adopted models used, are presented in this work. © 2013 Ana Paula Marins Chiaradia et al.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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This study presents a new recombinant protein that acts as a powerful antiviral (rAVLO—recombinant Antiviral protein of Lonomia obliqua). It was able to reduce the replication by 106 fold for herpes virus and by 104 fold for rubella virus. RT-PCR of viral RNA rAVLO treated infected cells also showed similar rate of inhibition in replication. The analysis of this protein by bioinformatics suggests that this protein is globular, secreted with a signal peptide and has the ability to bind to MHC class I. It was found that there are several protein binding sites with various HLA and a prevalence of α-helices in the N-terminal region (overall classified as a α/β protein type). BLAST similarity sequence search for corresponding cDNA did not reveal a similar sequence in Genbank, suggesting that it is from a novel protein family. In this study we have observed that this recombinant protein and hemolymph has a potent antiviral action. This protein was produced in a baculovirus/Sf-9 system. Therefore, these analyses suggest that this novel polypeptide is a candidate as a broad spectrum antiviral.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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