In silico network topology-based prediction of gene essentiality

The identification of genes essential for survival is important for the understanding of the minimal requirements for cellular life and for drug design. As experimental studies with the purpose of building a catalog of essential genes for a given organism are time-consuming and laborious, a computational approach which could predict gene essentiality with high accuracy would be of great value. We present here a novel computational approach, called NTPGE (Network Topology-based Prediction of Gene Essentiality), that relies on the network topology features of a gene to estimate its essentiality. The first step of NTPGE is to construct the integrated molecular network for a given organism comprising protein physical, metabolic and transcriptional regulation interactions. The second step consists in training a decision-tree-based machine-learning algorithm on known essential and non-essential genes of the organism of interest, considering as learning attributes the network topology information for each of these genes. Finally, the decision-tree classifier generated is applied to the set of genes of this organism to estimate essentiality for each gene. We applied the NTPGE approach for discovering the essential genes in Escherichia coli and then assessed its performance. (C) 2007 Elsevier B.V. All rights reserved.

Towards the prediction of essential genes by integration of network topology, cellular localization and biological process information

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

Prediction of Oncogenic Interactions and Cancer-Related Signaling Networks Based on Network Topology

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

Computational analysis and physico-chemical characterization of an inclusion compound between praziquantel and methyl-beta-cyclodextrin for use as an alternative in the treatment of schistosomiasis

Schistosomiasis is still an endemic disease in many regions, with 250 million people infected with Schistosoma and about 500,000 deaths per year. Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment, however it is classified as Class II in the Biopharmaceutics Classification System, as its low solubility hinders its performance in biological systems. The use of cyclodextrins is a useful tool to increase the solubility and bioavailability of drugs. The aim of this work was to prepare an inclusion compound of PZQ and methyl-beta-cyclodextrin (MeCD), perform its physico-chemical characterization, and explore its in vitro cytotoxicity. SEM showed a change of the morphological characteristics of PZQ:MeCD crystals, and IR data supported this finding, with changes after interaction with MeCD including effects on the C-H of the aromatic ring, observed at 758 cm(-1). Differential scanning calorimetry measurements revealed that complexation occurred in a 1:1 molar ratio, as evidenced by the lack of a PZQ transition temperature after inclusion into the MeCD cavity. In solution, the PZQ UV spectrum profile in the presence of MeCD was comparable to the PZQ spectrum in a hydrophobic solvent. Phase solubility diagrams showed that there was a 5.5-fold increase in PZQ solubility, and were indicative of a type A(L) isotherm, that was used to determine an association constant (K(a)) of 140.8 M(-1). No cytotoxicity of the PZQ:MeCD inclusion compound was observed in tests using 3T3 cells. The results suggest that the association of PZQ with MeCD could be a good alternative for the treatment of schistosomiasis.

A computational tool to assist the analysis of the transformer behavior related to lightning

This paper proposes the application of computational intelligence techniques to assist complex problems concerning lightning in transformers. In order to estimate the currents related to lightning in a transformer, a neural tool is presented. ATP has generated the training vectors. The input variables used in Artificial Neural Networks (ANN) were the wave front time, the wave tail time, the voltage variation rate and the output variable is the maximum current in the secondary of the transformer. These parameters can define the behavior and severity of lightning. Based on these concepts and from the results obtained, it can be verified that the overvoltages at the secondary of transformer are also affected by the discharge waveform in a similar way to the primary side. By using the tool developed, the high voltage process in the distribution transformers can be mapped and estimated with more precision aiding the transformer project process, minimizing empirics and evaluation errors, and contributing to minimize the failure rate of transformers. (C) 2011 Elsevier Ltd. All rights reserved.

Vacuum effects on massive spinor fields: S-1 x R-3 topology

The aim of this work was to investigate the role played by an external field on the Casimir energy density for massive fermions under S-1 x R-3 topology. Both twisted- and untwisted-spin connections are considered and the calculation in a closed form is performed using an alternative approach based on the combination of the analytic regularization method and the Euler-Maclaurin summation formula. It is shown that no mass scale appears in the final result and, therefore, Casimir effect arises only from the boundary conditions and vacuum fluctuations induced by the coupling with the external field.

Low voltage four-quadrant current multiplier: An improved topology for n-well CMOS process

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Algoritmos evolutivos dedicados à reconfiguração de redes radiais de distribuição sob demandas fixas e variáveis: estudo dos operadores genéticos e parâmetros de controle

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

Low voltage four-quadrant current multiplier: an improved topology for n-well CMOS process

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Monte Carlo thermodynamic and structural properties of the TIP4P water model: dependence on the computational conditions

Classical Monte Carlo simulations were carried out on the NPT ensemble at 25°C and 1 atm, aiming to investigate the ability of the TIP4P water model [Jorgensen, Chandrasekhar, Madura, Impey and Klein; J. Chem. Phys., 79 (1983) 926] to reproduce the newest structural picture of liquid water. The results were compared with recent neutron diffraction data [Soper; Bruni and Ricci; J. Chem. Phys., 106 (1997) 247]. The influence of the computational conditions on the thermodynamic and structural results obtained with this model was also analyzed. The findings were compared with the original ones from Jorgensen et al [above-cited reference plus Mol. Phys., 56 (1985) 1381]. It is notice that the thermodynamic results are dependent on the boundary conditions used, whereas the usual radial distribution functions g(O/O(r)) and g(O/H(r)) do not depend on them.

Strand Analysis, a free online program for the computational identification of the best RNA interference (RNAi) targets based on Gibbs free energy

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

The size of excavators within a polymorphic termite species governs tunnel topology

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

Structure of the posthepatic septum and its influence on visceral topology in the tegu lizard, Tupinambis merianae (Teiidae : Reptilia)

The posthepatic septum (PHS) divides the body cavity of Tupinambis merianae into two parts: the cranial one containing the lungs and liver and the caudal one containing the remaining viscera. The PHS is composed of layers of collagenous fibers and bundles of smooth muscle, neither of which show systematic orientation, as well as isolated blood vessels, lymphatic vessels, and nerves. Striated muscle of the abdominal wall does not invade the PHS. The contractions of the smooth muscles may stabilize the pleurohepatic cavity under conditions of elevated aerobic needs rather than supporting breathing on a breath-by-breath basis. Surgical removal of the PHS changes the anatomical arrangement of the viscera significantly, with stomach and intestine invading the former pleurohepatic cavity and reducing the space for the lungs, Thus, the PHS is essential to maintain the visceral topography in Tupitionibis. J. Morphol. 258:151-157, 2003. (C) 2003 Wiley-Liss. Inc.

Crotacetin, a novel snake venom C-type lectin homolog of convulxin, exhibits an unpredictable antimicrobial activity

Snake venom (sv) C-type lectins encompass a group of hemorrhagic toxins that are capable of interfering with blood stasis. A very well-studied svC-type lectin is the heterodimeric toxin, convulxin (CVX), from the venom of South American rattlesnake Crotalus durissus terrificus. CVX is able to activate platelets and induce their aggregation by acting via p62/GPVI collagen receptor. By using polymerase chain reaction homology screening, we have cloned several cDNA precursors of CVX subunit homologs. One of them, named crotacetin (CTC) beta-subunit, predicts a polypeptide with a topology very similar to the tridimensional conformations of other subunits of CVX-like snake toxins, as determined by computational analysis. Using gel permeation and reverse-phase high-performance liquid chromatography, CTC was purified from C. durissus venoms. CTC can be isolated from the venom of several C. durissus subspecies, but its quantitative predominance is in the venom of C. durissus cascavella. Functional analysis indicates that CTC induces platelet aggregation, and, importantly, exhibits an antimicrobial activity against Gram-positive and -negative bacteria, comparable with CVX.