Enzyme kinetics, structural analysis and molecular modeling studies on a series of Schistosoma mansoni PNP inhibitors

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the development of novel drugs against schistosomiasis, a neglected tropical disease that affects about 200 million people worldwide. In the present work, enzyme kinetic studies were carried out in order to determine the potency and mechanism of inhibition of a series of SmPNP inhibitors. In addition to the biochemical investigations, crystallographic and molecular modeling studies revealed important molecular features for binding affinity towards the target enzyme, leading to the development of structure-activity relationships (SAR).

Late Quaternary drainage dynamics in northern Brazil based on the study of a large paleochannel from southwestern Marajó Island

Marajó Island shows an abundance of paleochannels easily mapped in its eastern portion, where vegetation consists mostly of savannas. SRTM data make possible to recognize paleochannels also in western Marajó, even considering the dense forest cover. A well preserved paleodrainage network from the adjacency of the town of Breves (southwestern Marajó Island) was investigated in this work combining remote sensing and sedimentological studies. The palimpsest drainage system consists of a large meander connected to narrower tributaries. Sedimentological studies revealed mostly sharp-based, fining upward sands for the channelized features, and interbedded muds and sands for floodplain areas. The sedimentary structures and facies successions are in perfect agreement with deposition in channelized and floodplain environments, as suggested by remote sensing mapping. The present study shows that this paleodrainage was abandoned during Late Pleistocene, slightly earlier than the Holocene paleochannel systems from the east part of the island. Integration of previous studies with the data available herein supports a tectonic origin, related to the opening of the Pará River along fault lineaments. This would explain the disappearance of large, north to northeastward migrating channel systems in southwestern Marajó Island, which were replaced by the much narrower, south to southeastward flowing modern channels.

Modelagem matemática do controle de brucelose bovina por vacinação

As fêmeas bovinas, por sua importância na transmissão e na manutenção da brucelose, constituíram o alvo dos inquéritos do Programa Nacional de Controle e Erradicação da Brucelose e da Tuberculose Animal. Com base em informações obtidas em unidades federativas onde foram realizados inquéritos sorológicos e observadas prevalências de animais acima de 2%, elaborou-se um modelo para simular a dinâmica da brucelose em rebanhos bovinos formados exclusivamente por fêmeas, analisando o efeito de estratégias de vacinação. Para baixa cobertura vacinal, da ordem de 30%, o tempo para reduzir a prevalência a 2%, valor adotado como referência, pode ser longo, aproximando-se do dobro do tempo necessário para uma cobertura mais alta, de 90%. De acordo com o modelo, o tempo para reduzir a prevalência a 1% ou 2%, que permitam passar à fase de erradicação, pode chegar a uma década. Recomenda-se a intensificação do esforço para a vacinação de fêmeas, procurando atingir alta cobertura vacinal.

Body Mass Index, Cigarette Smoking, and Alcohol Consumption and Cancers of the Oral Cavity, Pharynx, and Larynx: Modeling Odds Ratios in Pooled Case-Control Data

study-specific results, their findings should be interpreted with caution

Unconstrained Finite Element for Geometrical Nonlinear Dynamics of Shells

This paper presents a positional FEM formulation to deal with geometrical nonlinear dynamics of shells. The main objective is to develop a new FEM methodology based on the minimum potential energy theorem written regarding nodal positions and generalized unconstrained vectors not displacements and rotations. These characteristics are the novelty of the present work and avoid the use of large rotation approximations. A nondimensional auxiliary coordinate system is created, and the change of configuration function is written following two independent mappings from which the strain energy function is derived. This methodology is called positional and, as far as the authors' knowledge goes, is a new procedure to approximated geometrical nonlinear structures. In this paper a proof for the linear and angular momentum conservation property of the Newmark beta algorithm is provided for total Lagrangian description. The proposed shell element is locking free for elastic stress-strain relations due to the presence of linear strain variation along the shell thickness. The curved, high-order element together with an implicit procedure to solve nonlinear equations guarantees precision in calculations. The momentum conserving, the locking free behavior, and the frame invariance of the adopted mapping are numerically confirmed by examples. Copyright (C) 2009 H. B. Coda and R. R. Paccola.

UNIQUENESS AND NONUNIQUENESS RESULTS FOR A CERTAIN CLASS OF ALMOST PERIODIC DISTRIBUTIONS

We consider distributions u is an element of S'(R) of the form u(t) = Sigma(n is an element of N) a(n)e(i lambda nt), where (a(n))(n is an element of N) subset of C and Lambda = (lambda n)(n is an element of N) subset of R have the following properties: (a(n))(n is an element of N) is an element of s', that is, there is a q is an element of N such that (n(-q) a(n))(n is an element of N) is an element of l(1); for the real sequence., there are n(0) is an element of N, C > 0, and alpha > 0 such that n >= n(0) double right arrow vertical bar lambda(n)vertical bar >= Cn(alpha). Let I(epsilon) subset of R be an interval of length epsilon. We prove that for given Lambda, (1) if Lambda = O(n(alpha)) with alpha < 1, then there exists epsilon > 0 such that u vertical bar I(epsilon) = 0 double right arrow u 0; (2) if Lambda = O(n) is uniformly discrete, then there exists epsilon > 0 such that u vertical bar I(epsilon) = 0 double right arrow u 0; (3) if alpha > 1 and. is uniformly discrete, then for all epsilon > 0, u vertical bar I(epsilon) = 0 double right arrow u = 0. Since distributions of the above mentioned form are very common in engineering, as in the case of the modeling of ocean waves, signal processing, and vibrations of beams, plates, and shells, those uniqueness and nonuniqueness results have important consequences for identification problems in the applied sciences. We show an identification method and close this article with a simple example to show that the recovery of geometrical imperfections in a cylindrical shell is possible from a measurement of its dynamics.

Dynamical models for computer viruses propagation

Nowadays, digital computer systems and networks are the main engineering tools, being used in planning, design, operation, and control of all sizes of building, transportation, machinery, business, and life maintaining devices. Consequently, computer viruses became one of the most important sources of uncertainty, contributing to decrease the reliability of vital activities. A lot of antivirus programs have been developed, but they are limited to detecting and removing infections, based on previous knowledge of the virus code. In spite of having good adaptation capability, these programs work just as vaccines against diseases and are not able to prevent new infections based on the network state. Here, a trial on modeling computer viruses propagation dynamics relates it to other notable events occurring in the network permitting to establish preventive policies in the network management. Data from three different viruses are collected in the Internet and two different identification techniques, autoregressive and Fourier analyses, are applied showing that it is possible to forecast the dynamics of a new virus propagation by using the data collected from other viruses that formerly infected the network. Copyright (c) 2008 J. R. C. Piqueira and F. B. Cesar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The role of disulfide bridges in the 3-D structures of the antimicrobial peptides gomesin and protegrin-1: a molecular dynamics study

Some antimicrobial peptides have a broad spectrum of action against many different kinds of microorganisms. Gomesin and protegrin-1 are examples of such antimicrobial peptides, and they were studied by molecular dynamics in this research. Both have a beta-hairpin conformation stabilized by two disulfide bridges and are active against Gram-positive and Gram-negative bacteria, as well as fungi. In this study, the role of the disulfide bridge in the maintenance of the tertiary peptide structure of protegrin-1 and gomesin is analyzed by the structural characteristics of these peptides and two of their respective variants, gomy4 and proty4, in which the four cysteines are replaced by four tyrosine residues. The absence of disulfide bridges in gomy4 and proty4 is compensated by overall reinforcement of the original hydrogen bonds and extra attractive interactions between the aromatic rings of the tyrosine residues. The net effects on the variants with respect to the corresponding natural peptides are: i) maintenance of the original beta-hairpin conformation, with great structural similarities between the mutant and the corresponding natural peptide; ii) combination of positive F and. Ramachandran angles within the hairpin head region with a qualitative change to a combination of positive (F) and negative (.) angles, and iii) significant increase in structural flexibility. Experimental facts about the antimicrobial activity of the gomesin and protegrin-1 variants have also been established here, in the hope that the detailed data provided in the present study may be useful for understanding the mechanism of action of these peptides.

Study of the antimicrobial peptide indolicidin and a mutant in micelle medium by molecular dynamics simulation

The antimicrobial peptide indolicidin (IND) and the mutant CP10A in hydrated micelles were studied using molecular dynamics simulations in order to observe whether the molecular dynamics and experimental data could be sufficiently correlated and a detailed description of the interaction of the antimicrobial peptides with a model of the membrane provided by a hydrated micelle system could be obtained. In agreement with the experiments, the simulations showed that the peptides are located near the surface of the micelles. Peptide insertions agree with available experimental data, showing deeper insertion of the mutant compared with the peptide IND. Major insertion into the hydrophobic core of the micelle by all tryptophan and mutated residues of CP10A in relation to IND was observed. The charged residues of the terminus regions of both peptides present similar behavior, indicating that the major differences in the interactions with the micelles of the peptides IND and CP10A occur in the case of the hydrophobic residues.

Pulse train fluorescence technique for measuring triplet state dynamics

We report on a method to study the dynamics of triplet formation based on the fluorescence signal produced by a pulse train. Basically, the pulse train acts as sequential pump-probe pulses that precisely map the excited-state dynamics in the long time scale. This allows characterizing those processes that affect the population evolution of the first excited singlet state, whose decay gives rise to the fluorescence. The technique was proven to be valuable to measure parameters of triplet formation in organic molecules. Additionally, this single beam technique has the advantages of simplicity, low noise and background-free signal detection. (C) 2011 Optical Society of America

Brazilian territorial dynamics and the inversion of the ""frontier thesis"" in the southern new world

It is a generally acknowledged fact that the dynamics of frontier advance deeply influenced the broad experience of American post colonial societies. The colonization, which started most from the east boundaries of the continent, appropriated and gradually transformed the American territories from east to west. The advance, initially represented by the arrival of the European settlers, went on to become an important trace of that society which did not come to know any physical limits of a restricted territory. However, despite the common identity granted by these territorial dynamics, the later developments and consequences seem to have shaped differently the Northern representatives from their Southern counterparts. In addition, the interpretation of these facts bore in each of these regions different meanings and traits.

Modeling the risk of malaria for travelers to areas with stable malaria transmission

Background: Malaria is an important threat to travelers visiting endemic regions. The risk of acquiring malaria is complex and a number of factors including transmission intensity, duration of exposure, season of the year and use of chemoprophylaxis have to be taken into account estimating risk. Materials and methods: A mathematical model was developed to estimate the risk of non-immune individual acquiring falciparum malaria when traveling to the Amazon region of Brazil. The risk of malaria infection to travelers was calculated as a function of duration of exposure and season of arrival. Results: The results suggest significant variation of risk for non-immune travelers depending on arrival season, duration of the visit and transmission intensity. The calculated risk for visitors staying longer than 4 months during peak transmission was 0.5% per visit. Conclusions: Risk estimates based on mathematical modeling based on accurate data can be a valuable tool in assessing risk/benefits and cost/benefits when deciding on the value of interventions for travelers to malaria endemic regions.

Notes on Population Dynamics of Amblyomma Ticks (Acari: Ixodidae) in Brazil

Previous population dynamics data, generated for Amblyomma parvum Aragao and Aniblyomma cajennense (Fabricius) in Argentina and southeastern Brazil, have indicated that these ticks complete I generation per year, with larvae predominating in autumn, nymphs in winter, and mostly adults during spring and summer. The present study reports population dynamics data for free-living Amblyomma spp. ticks in northern Brazil (Amazon forest, latitude 10 degrees S, 63 degrees W), and for Amblyomma spp. ticks collected oil birds in Southeastern Brazil (latitude 23 degrees S, 45 degrees W). In northern Brazil, adult ticks predominated from mid-spring to mid-autumn, larvae predominated in early winter, and nymphs from mid-winter to mid-spring. Seven Amblyomma spp. were identified, although A. cajannense predominated in I of the 2 sites sampled. In southeastern Brazil, larval infestations on birds peaked in autumn, followed by a nymphal infestation peak in late winter. At least 32% and 75% of these larvae and nymphs, respectively, were identified as Amblyomma longirostre (Koch). Similar to previous work, the present study showed that Amblyomma spp. larvae and nymphs predominated during autumn-winter months, and mostly adults during spring-summer months, a pattern compatible with 1 genration/yr, even at latitude 10 degrees S in northern Brazil.

The structure and dynamics of Abell 1942

Aims. We present a dynamical analysis of the galaxy cluster Abell 1942 based on a set of 128 velocities obtained at the European Southern Observatory. Methods. Data on individual galaxies are presented and the accuracy of the determined velocities as some properties of the cluster are discussed. We have also made use of publicly available Chandra X-ray data. Results. We obtained an improved mean redshift value z = 0.22513 +/- 0.0008 and velocity dispersion sigma = 908(139)(+147) km s(-1). Our analysis indicates that inside a radius of similar to 1.5 h(70)(-1) Mpc (similar to 7 arcmin) the cluster is well relaxed, without any remarkable features and the X-ray emission traces the galaxy distribution fairly well. Two possible optical substructures are seen at similar to 5 arcmin from the centre in the northwest and the southwest directions, but are not confirmed by the velocity field. These clumps are, however, kinematically bound to the main structure of Abell 1942. X-ray spectroscopic analysis of Chandra data resulted in a temperature kT = 5.5+/-0.5 keV and metal abundance Z = 0.33 +/- 0.15 Z(circle dot). The velocity dispersion corresponding to this temperature using the T(X-sigma) scaling relation is in good agreement with the measured galaxy velocities. Our photometric redshift analysis suggests that the weak lensing signal observed to the south of the cluster and previously attributed to a ""dark clump"" is produced by background sources, possibly distributed as a filamentary structure.

Dynamics and constraints of the massive graviton dark matter flat cosmologies

We discuss the dynamics of the Universe within the framework of the massive graviton cold dark matter scenario (MGCDM) in which gravitons are geometrically treated as massive particles. In this modified gravity theory, the main effect of the gravitons is to alter the density evolution of the cold dark matter component in such a way that the Universe evolves to an accelerating expanding regime, as presently observed. Tight constraints on the main cosmological parameters of the MGCDM model are derived by performing a joint likelihood analysis involving the recent supernovae type Ia data, the cosmic microwave background shift parameter, and the baryonic acoustic oscillations as traced by the Sloan Digital Sky Survey red luminous galaxies. The linear evolution of small density fluctuations is also analyzed in detail. It is found that the growth factor of the MGCDM model is slightly different (similar to 1-4%) from the one provided by the conventional flat Lambda CDM cosmology. The growth rate of clustering predicted by MGCDM and Lambda CDM models are confronted to the observations and the corresponding best fit values of the growth index (gamma) are also determined. By using the expectations of realistic future x-ray and Sunyaev-Zeldovich cluster surveys we derive the dark matter halo mass function and the corresponding redshift distribution of cluster-size halos for the MGCDM model. Finally, we also show that the Hubble flow differences between the MGCDM and the Lambda CDM models provide a halo redshift distribution departing significantly from the those predicted by other dark energy models. These results suggest that the MGCDM model can observationally be distinguished from Lambda CDM and also from a large number of dark energy models recently proposed in the literature.