Use of self-organizing maps and molecular descriptors to predict the cytotoxic activity of sesquiterpene lactones

Some sesquiterpene lactones (SLs) are the active compounds of a great number of traditionally medicinal plants from the Asteraceae family and possess considerable cytotoxic activity. Several studies in vitro have shown the inhibitory activity against cells derived from human carcinoma of the nasopharynx (KB). Chemical studies showed that the cytotoxic activity is due to the reaction of alpha,beta-unsaturated carbonyl structures of the SLs with thiols, such as cysteine. These studies support the view that SLs inhibit tumour growth by selective alkylation of growth-regulatory biological macromolecules, such as key enzymes, which control cell division, thereby inhibiting a variety of cellular functions, which directs the cells into apoptosis. In this study we investigated a set of 55 different sesquiterpene lactones, represented by 5 skeletons (22 germacranolides, 6 elemanolides, 2 eudesmanolides, 16 guaianolides and nor-derivatives and 9 pseudoguaianolides), in respect to their cytotoxic properties. The experimental results and 3D molecular descriptors were submitted to Kohonen self-organizing map (SOM) to classify (training set) and predict (test set) the cytotoxic activity. From the obtained results, it was concluded that only the geometrical descriptors showed satisfactory values. The Kohonen map obtained after training set using 25 geometrical descriptors shows a very significant match, mainly among the inactive compounds (similar to 84%). Analyzing both groups, the percentage seen is high (83%). The test set shows the highest match, where 89% of the substances had their cytotoxic activity correctly predicted. From these results, important properties for the inhibition potency are discussed for the whole dataset and for subsets of the different structural skeletons. (C) 2008 Elsevier Masson SAS. All rights reserved.

Three-Dimensional Stress Distribution in the Human Periodontal Ligament in Masticatory, Parafunctional, and Trauma Loads: Finite Element Analysis

Background: The presence of the periodontal ligament (PDL) makes it possible to absorb and distribute loads produced during masticatory function and other tooth contacts into the alveolar process via the alveolar bone proper. However, several factors affect the integrity of periodontal structures causing the destruction of the connective matrix and cells, the loss of fibrous attachment, and the resorption of alveolar bone. Methods: The purpose of this study was to evaluate the stress distribution by finite element analysis in a PDL in three-dimensional models of the upper central incisor under three different load conditions: 100 N occlusal loading at 45 degrees (model 1: masticatory load); 500 N at the incisal edge at 45 degrees (model 2: parafunctional habit); and 800 N at the buccal surface at 90 degrees (model 3: trauma case). The models were built from computed tomography scans. Results: The stress distribution was quite different among the models. The most significant values (harmful) of tensile and compressive stresses were observed in models 2 and 3, with similarly distinct patterns of stress distributions along the PDL. Tensile stresses were observed along the internal and external aspects of the PDL, mostly at the cervical and middle thirds. Conclusions: The stress generation in these models may affect the integrity of periodontal structures. A better understanding of the biomechanical behavior of the PDL under physiologic and traumatic loading conditions might enhance the understanding of the biologic reaction of the PDL in health and disease. J Periodontol 2009;80:1859-1867.

A hybrid-mixed finite element formulation for the geometrically exact analysis of three-dimensional framed structures

This paper addresses the development of a hybrid-mixed finite element formulation for the quasi-static geometrically exact analysis of three-dimensional framed structures with linear elastic behavior. The formulation is based on a modified principle of stationary total complementary energy, involving, as independent variables, the generalized vectors of stress-resultants and displacements and, in addition, a set of Lagrange multipliers defined on the element boundaries. The finite element discretization scheme adopted within the framework of the proposed formulation leads to numerical solutions that strongly satisfy the equilibrium differential equations in the elements, as well as the equilibrium boundary conditions. This formulation consists, therefore, in a true equilibrium formulation for large displacements and rotations in space. Furthermore, this formulation is objective, as it ensures invariance of the strain measures under superposed rigid body rotations, and is not affected by the so-called shear-locking phenomenon. Also, the proposed formulation produces numerical solutions which are independent of the path of deformation. To validate and assess the accuracy of the proposed formulation, some benchmark problems are analyzed and their solutions compared with those obtained using the standard two-node displacement/ rotation-based formulation.

Some (3+1)-dimensional vortex solutions of the CP(N) model

We present a class of solutions of the CP(N) model in (3 + 1) dimensions. We suggest that they represent vortexlike configurations. We also discuss some of their properties. We show that some configurations of vortices have a divergent energy per unit length while for the others such an energy has a minimum for a very special orientation of vortices. We also discuss the Noether charge densities of these vortices.

Aerodynamic study of three-dimensional larynx models using finite element methods

The airflow velocities and pressures are calculated from a three-dimensional model of the human larynx by using the finite element method. The laryngeal airflow is assumed to be incompressible, isothermal, steady, and created by fixed pressure drops. The influence of different laryngeal profiles (convergent, parallel, and divergent), glottal area, and dimensions of false vocal folds in the airflow are investigated. The results indicate that vertical and horizontal phase differences in the laryngeal tissue movements are influenced by the nonlinear pressure distribution across the glottal channel, and the glottal entrance shape influences the air pressure distribution inside the glottis. Additionally, the false vocal folds increase the glottal duct pressure drop by creating a new constricted channel in the larynx, and alter the airflow vortexes formed after the true vocal folds. (C) 2007 Elsevier Ltd. All rights reserved.

Inverse analysis FOR two-dimensional structures using the boundary element method

Inverse analysis is currently an important subject of study in several fields of science and engineering. The identification of physical and geometric parameters using experimental measurements is required in many applications. In this work a boundary element formulation to identify boundary and interface values as well as material properties is proposed. In particular the proposed formulation is dedicated to identifying material parameters when a cohesive crack model is assumed for 2D problems. A computer code is developed and implemented using the BEM multi-region technique and regularisation methods to perform the inverse analysis. Several examples are shown to demonstrate the efficiency of the proposed model. (C) 2010 Elsevier Ltd. All rights reserved,

Analyzing static three-dimensional elastic domains with a new infinite boundary element formulation

A new two-dimensionally mapped infinite boundary element (IBE) is presented. The formulation is based on a triangular boundary element (BE) with linear shape functions instead of the quadrilateral IBEs usually found in the literature. The infinite solids analyzed are assumed to be three-dimensional, linear-elastic and isotropic, and Kelvin fundamental solutions are employed. One advantage of the proposed formulation over quadratic or higher order elements is that no additional degrees of freedom are added to the original BE mesh by the presence of the IBEs. Thus, the IBEs allow the mesh to be reduced without compromising the accuracy of the result. Two examples are presented, in which the numerical results show good agreement with authors using quadrilateral IBEs and analytical solutions. (C) 2010 Elsevier Ltd. All rights reserved.

GENERALIZED FINITE ELEMENT METHOD FOR NONLINEAR THREE-DIMENSIONAL ANALYSIS OF SOLIDS

The Generalized Finite Element Method (GFEM) is employed in this paper for the numerical analysis of three-dimensional solids tinder nonlinear behavior. A brief summary of the GFEM as well as a description of the formulation of the hexahedral element based oil the proposed enrichment strategy are initially presented. Next, in order to introduce the nonlinear analysis of solids, two constitutive models are briefly reviewed: Lemaitre`s model, in which damage and plasticity are coupled, and Mazars`s damage model suitable for concrete tinder increased loading. Both models are employed in the framework of a nonlocal approach to ensure solution objectivity. In the numerical analyses carried out, a selective enrichment of approximation at regions of concern in the domain (mainly those with high strain and damage gradients) is exploited. Such a possibility makes the three-dimensional analysis less expensive and practicable since re-meshing resources, characteristic of h-adaptivity, can be minimized. Moreover, a combination of three-dimensional analysis and the selective enrichment presents a valuable good tool for a better description of both damage and plastic strain scatterings.

Shell curvature as an initial deformation: A geometrically exact finite element approach

An alternative approach for the analysis of arbitrarily curved shells is developed in this paper based on the idea of initial deformations. By `alternative` we mean that neither differential geometry nor the concept of degeneration is invoked here to describe the shell surface. We begin with a flat reference configuration for the shell mid-surface, after which the initial (curved) geometry is mapped as a stress-free deformation from the plane position. The actual motion of the shell takes place only after this initial mapping. In contrast to classical works in the literature, this strategy enables the use of only orthogonal frames within the theory and therefore objects such as Christoffel symbols, the second fundamental form or three-dimensional degenerated solids do not enter the formulation. Furthermore, the issue of physical components of tensors does not appear. Another important aspect (but not exclusive of our scheme) is the possibility to describe exactly the initial geometry. The model is kinematically exact, encompasses finite strains in a totally consistent manner and is here discretized under the light of the finite element method (although implementation via mesh-free techniques is also possible). Assessment is made by means of several numerical simulations. Copyright (C) 2009 John Wiley & Sons, Ltd.

3`3-Ditrifluoromethyldiphenyl diselenide: A new organoselenium compound with interesting antigenotoxic and antimutagenic activities

The trace element selenium (Se), once known only for its potential toxicity, is now a well-established essential micronutrient for mammals. The organoselenium compound diphenyl diselenide (DPDS) has shown interesting antioxidant and neuroprotective activities. On the other hand, this compound has also presented pro-oxidant and mutagenic effects. The compound 3`3-ditrifluoromethyldiphenyl diselenide (DFDD), a structural analog of diphenyl diselenide, has proven antipsychotic activity in mice. Nevertheless, as opposed to DPDS, little is known on the biological and toxicological properties of DFDD. In the present study, we report the genotoxic effects of the organoselenium compound DFDD on Salmonella typhimurium, Saccharomyces cerevisiae and Chinese hamster lung fibroblasts (V79 cells). DFDD protective effects against hydrogen peroxide (H(2)O(2))-induced DNA damage in vitro are demonstrated. DFDD did not cause mutagenic effects on S. typhimurium or S. cerevisiae strains; however, it induced DNA damage in V79 cells at doses higher than 25 mu M, as detected by comet assay. DFDD protected S. typhimurium and S. cerevisiae against H(2)O(2)-induced mutagenicity, and, at doses lower than 12.5 mu M, prevented H(2)O(2)-induced genotoxicity in V79 cells. The in vitro assays demonstrated that DFDD mimics catalase activity better than DPDS, but neither presents Superoxide dismutase action. The products of the reactions of DFDD or DPDS with H(2)O(2) were different. as determined by electrospray mass spectrometry analysis (ESI-MS). These results suggest that DFDD is not mutagenic for bacteria or yeast; however, it may induce weak genotoxic effects on mammalian cells. In addition, DFDD has a protective effect against H(2)O(2)-induced damage probably by mimicking catalase activity, and the distinct products of the reaction DFDD with H(2)O(2) probably have a fundamental role in the protective effects of DFDD. (C) 2009 Elsevier B.V. All rights reserved.

Two distinct regions in 2q24.2-q24.3 associated with idiopathic epilepsy

P>Approximately 50% of all carriers of 2q21-q31 deletions present epileptic seizures. The band 2q24 constitutes the smallest commonly deleted segment in these patients, and contains the voltage-gated sodium channel genes SCN1A and SCN2A, associated with Dravet syndrome and benign familial neonatal-infantile seizures, respectively. A further putative locus involving epilepsy in the region was previously identified through disruption of the SLC4A10 gene by translocation. In the course of performing high-resolution DNA copy number analyses on syndromic mentally impaired individuals, we encountered three patients with overlapping deletions in chromosome region 2q24. Two of these patients exhibited epileptic seizures in addition to mental deficiency. The deletion in one of the epileptic patients did not include the SCN cluster, demonstrating that a less severe form of epilepsy maps to an adjacent genomic region. This second region comprises about 3 Mb and contains the candidate gene SLC4A10, providing further support for the potential role of this gene in epilepsy.

Finite Element Analysis of Shear Versus Torsion Adhesive Strength Tests for Dental Resin Composites

Stress distributions in torsion and wire-loop shear tests were compared using three-dimensional (3-D) linear-elastic finite element method, in an attempt to predict the ideal conditions for testing adhesive strength of dental resin composites to dentin. The torsion test presented lower variability in stress concentration at the adhesive interface with changes in the proportion adhesive thickness/resin composite diameter, as well as lower variability with changes in the resin composite elastic modulus. Moreover, the torsion test eliminated variability from changes in loading distance, and reduced the cohesive fracture tendency in the dentin. The torsion test seems to be more appropriate than wire-loop shear test for testing the resin composite-tooth interface strength. (c) Koninklijke Brill NV, Leiden, 2009

Foliations and polynomial diffeomorphisms of R(3)

Let Y = (f, g, h): R(3) -> R(3) be a C(2) map and let Spec(Y) denote the set of eigenvalues of the derivative DY(p), when p varies in R(3). We begin proving that if, for some epsilon > 0, Spec(Y) boolean AND (-epsilon, epsilon) = empty set, then the foliation F(k), with k is an element of {f, g, h}, made up by the level surfaces {k = constant}, consists just of planes. As a consequence, we prove a bijectivity result related to the three-dimensional case of Jelonek`s Jacobian Conjecture for polynomial maps of R(n).

Numerical solution of the PTT constitutive equation for unsteady three-dimensional free surface flows

This work deals with the development of a numerical technique for simulating three-dimensional viscoelastic free surface flows using the PTT (Phan-Thien-Tanner) nonlinear constitutive equation. In particular, we are interested in flows possessing moving free surfaces. The equations describing the numerical technique are solved by the finite difference method on a staggered grid. The fluid is modelled by a Marker-and-Cell type method and an accurate representation of the fluid surface is employed. The full free surface stress conditions are considered. The PTT equation is solved by a high order method, which requires the calculation of the extra-stress tensor on the mesh contours. To validate the numerical technique developed in this work flow predictions for fully developed pipe flow are compared with an analytic solution from the literature. Then, results of complex free surface flows using the FIT equation such as the transient extrudate swell problem and a jet flowing onto a rigid plate are presented. An investigation of the effects of the parameters epsilon and xi on the extrudate swell and jet buckling problems is reported. (C) 2010 Elsevier B.V. All rights reserved.

U-Pb-Hf-trace element systematics and geochronology of zircon from a granulite-facies metamorphosed mafic-ultramafic layered complex in Central Brazil

Zircon recrystallization is a common process during high-grade metamorphism and promotes partial or complete resetting of the original isotopic and chemical characteristics of the mineral and thus complicates U-Pb geochronological interpretation. In Central Brazil, this complexity may be illustrated by three composite mafic-ultramafic intrusions metamorphosed under amphibolite-to-granulite conditions. Their ages of emplacement and metamorphic ages have been a matter of controversy for the last thirty years. The Serra da Malacacheta and Barro Alto complexes make up the southernmost of these layered bodies and four samples from distinct rock types were investigated in order to verify the consequences of metamorphic alteration of zircon for U-Pb dating. Cathodoluminescent imaging reveals internal features which are typical of concomitant dissolution-reprecipitation processes, such as convolute zoning and inward-moving recrystallization fronts, even in samples in which partially preserved igneous textures are observed. Due to this extensive alteration, LA-ICPMS U-Pb isotopic analysis yielded inconclusive data. However, in situ Hf isotopic and trace-element analyses help to clarify the real meaning of the geochronological data. Low Lu/Hf (<0.004) and homogeneous (176)Hf/(177)Hf(t) values imply that the zircon populations within individual samples have crystallized in a single episode, despite the observed variations in age values. Trace element signatures of zircon grains from garnet-bearing samples reveal that they were unreactive to the development of the peak metamorphism mineral assemblage and, thus, the main chemical feature in such grains is attributed to a coupled dissolution-reprecipitation process. However, in the Cafelandia amphibolite an additional alteration process is identified, probably related to the influx of late-stage fluids. Combined isotopic and geochemical investigation on zircon grains allowed the distinction of two magmatic events. The first corresponds to the crystallization of the Serra da Malacacheta Complex and characterizes a juvenile magmatism at similar to 1.3 Ga. The younger episode, recognized in the Barro Alto Complex, is dated at ca. 800 Ma and is represented by mafic and ultramafic rocks showing intense contamination with continental crust, implying that the emplacement took place, most likely, in a continental back-arc setting. Altered zircon domains as well as titanite grains date the metamorphic event at ca. 760-750 Ma. (C) 2011 Elsevier B.V. All rights reserved.