Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise do efeito higrotérmico no comportamento em fadiga de compósitos de PPS/fibras de carbono

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

The semisynthetic landscape of aphidicolin: inspiration towards leishmanicidal compounds

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

Structural bioinformatics study of PNP from Schistosoma mansoni

The parasite Schistosoma mansoni lacks the de novo pathway for purine biosynthesis and depends on salvage pathways for its purine requirements. Schistosomiasis is endemic in 76 countries and territories and amongst the parasitic diseases ranks second after malaria in terms of social and economic impact and public health importance. The PNP is an attractive target for drug design and it has been submitted to extensive structure-based design. The atomic coordinates of the complex of human PNP with inosine were used as template for starting the modeling of PNP from S. mansoni complexed with inosine. Here we describe the model for the complex SmPNP-inosine and correlate the structure with differences in the affinity for inosine presented by human and S. mansoni PNPs. (C) 2004 Elsevier B.V. All rights reserved.

Interfacial surface charge and free accessibility to the PLA(2)-active site-like region are essential requirements for the activity of Lys49 PLA(2) homologues

Lys49 phospholipase A(2) homologues are highly myotoxic and cause extensive tissue damage but do not display hydrolytic activity towards natural phospholipids. The binding of heparin, heparin derivatives and polyanionic compounds such as suramin result in partial inhibition (up to 60%) of the myotoxic effects due to a change in the overall charge of the interfacial surface. In vivo experiments demonstrate that polyethylene glycol inhibits more than 90% of the myotoxic effects without exhibiting secondary toxic effects. The crystal structure of bothropstoxin-I complexed with polyethylene glycol reveals that this inhibition is due to steric hindrance of the access to the PLA(2)-active site-like region. These two inhibitory pathways indicate the roles of the overall surface charge and free accessibility to the PLA2-active site-like region in the functioning of Lys49 phospholipases A(2) homologues. Molecular dynamics simulations, small angle X-ray scattering and structural analysis indicate that the oligomeric states both in solution and in the crystalline states of Lys49 phospholipases A2 are principally mediated by hydrophobic contacts formed between the interfacial surfaces. These results provide the framework for the potential application of both clinically approved drugs for the treatment of Viperidae snakebites. (c) 2006 Elsevier Ltd. All rights reserved.

Identification of structural parameters for active vibration control

The study of algorithms for active vibration control in flexible structures became an area of enormous interest for some researchers due to the innumerable requirements for better performance in mechanical systems, as for instance, aircrafts and aerospace structures. Intelligent systems, constituted for a base structure with sensors and actuators connected, are capable to guarantee the demanded conditions, through the application of diverse types of controllers. For the project of active controllers it is necessary, in general, to know a mathematical model that enable the representation in the space of states, preferential in modal coordinates to permit the truncation of the system and reduction in the order of the controllers. For practical applications of engineering, some mathematical models based in discrete-time systems cannot represent the physical problem, therefore, techniques of identification of system parameters must be used. The techniques of identification of parameters determine the unknown values through the manipulation of the input (disturbance) and output (response) signals of the system. Recently, some methods have been proposed to solve identification problems although, none of them can be considered as being universally appropriate to all the situations. This paper is addressed to an application of linear quadratic regulator controller in a structure where the damping, stiffness and mass matrices were identified through Chebyshev's polynomial functions.

Complete genome sequence and structural characterization of a novel iflavirus isolated from Opsiphanes invirae (Lepidoptera: Nymphalidae)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)