A comparison between PML, infinite elements and an iterative BEM as mesh truncation methods for HP self-adaptive procedures in electromagnetics

Finite element hp-adaptivity is a technology that allows for very accurate numerical solutions. When applied to open region problems such as radar cross section prediction or antenna analysis, a mesh truncation method needs to be used. This paper compares the following mesh truncation methods in the context of hp-adaptive methods: Infinite Elements, Perfectly Matched Layers and an iterative boundary element based methodology. These methods have been selected because they are exact at the continuous level (a desirable feature required by the extreme accuracy delivered by the hp-adaptive strategy) and they are easy to integrate with the logic of hp-adaptivity. The comparison is mainly based on the number of degrees of freedom needed for each method to achieve a given level of accuracy. Computational times are also included. Two-dimensional examples are used, but the conclusions directly extrapolated to the three dimensional case.

Numerical modelling of double diffusion driven reactive flow transport in deformable fluid-saturated porous media with particular consideration of temperature-dependent chemical reaction rates

Numerical methods ave used to solve double diffusion driven reactive flow transport problems in deformable fluid-saturated porous media. in particular, thp temperature dependent reaction rate in the non-equilibrium chemical reactions is considered. A general numerical solution method, which is a combination of the finite difference method in FLAG and the finite element method in FIDAP, to solve the fully coupled problem involving material deformation, pore-fluid flow, heat transfer and species transport/chemical reactions in deformable fluid-saturated porous media has been developed The coupled problem is divided into two subproblems which are solved interactively until the convergence requirement is met. Owing to the approximate nature of the numerical method, if is essential to justify the numerical solutions through some kind of theoretical analysis. This has been highlighted in this paper The related numerical results, which are justified by the theoretical analysis, have demonstrated that the proposed solution method is useful for and applicable to a wide range of fully coupled problems in the field of science and engineering.

Effects of hot intrusions on pore-fluid flow and heat transfer in fluid-saturated rocks

We use the finite element method to solve coupled problems between pore-fluid flow and heat transfer in fluid-saturated porous rocks. In particular, we investigate the effects of both the hot pluton intrusion and topographically driven horizontal flow on the distributions of the pore-flow velocity and temperature in large-scale hydrothermal systems. Since general mineralization patterns are strongly dependent on distributions of both the pore-fluid velocity and temperature fields, the modern mineralization theory has been used to predict the general mineralization patterns in several realistic hydrothermal systems. The related numerical results have demonstrated that: (1) The existence of a hot intrusion can cause an increase in the maximum value of the pore-fluid velocity in the hydrothermal system. (2) The permeability of an intruded pluton is one of the sensitive parameters to control the pore-fluid flow, heat transfer and ore body formation in hydrothermal systems. (3) The maximum value of the pore-fluid velocity increases when the bottom temperature of the hydrothermal system is increased. (4) The topographically driven flow has significant effects on the pore-fluid flow, temperature distribution and precipitation pattern of minerals in hydrothermal systems. (5) The size of the computational domain may have some effects on the pore-fluid flow and heat transfer, indicating that the size of a hydrothermal system may affect the pore-fluid flow and heat transfer within the system. (C) 2003 Elsevier Science B.V. All rights reserved.

Critical Velocity obtained using Simplified Models of the Railway Track: Viability and Applicability

Increased demands on the capacity of the railway network gave rise to new issues related to the dynamic response of railway tracks subjected to moving vehicles. Thus, it becomes important to evaluate the applicability of traditionally used simplified models which have a closed form solution. Regarding simplified models, transversal vibrations of a beam on a visco-elastic foundation subjected to a moving load are considered. Governing equations are obtained by Hamilton’s principle. Shear distortion, rotary inertia and effect of axial force are accounted for. The load is introduced as a time varying force moving at a constant velocity. Transversal vibrations induced by the load are solved by the normal-mode analysis. Reflected waves at the extremities of the full beam are avoided by introduction of semi-infinite elements. Firstly, the critical velocity obtained from this model is compared with results of an undamped Euler- Bernoulli formulation with zero axial force. Secondly, a finite element model in ABAQUS is examined. The new contribution lies in the introduction of semi- infinite elements and in the first step to a systematic comparison, which have not been published so fa

Combining a Similar Coefficient Identification Algorithm with the Boundary Element Method

The boundary element method (BEM) has been applied successfully to many engineering problems during the last decades. Compared with domain type methods like the finite element method (FEM) or the finite difference method (FDM) the BEM can handle problems where the medium extends to infinity much easier than domain type methods as there is no need to develop special boundary conditions (quiet or absorbing boundaries) or infinite elements at the boundaries introduced to limit the domain studied. The determination of the dynamic stiffness of arbitrarily shaped footings is just one of these fields where the BEM has been the method of choice, especially in the 1980s. With the continuous development of computer technology and the available hardware equipment the size of the problems under study grew and, as the flop count for solving the resulting linear system of equations grows with the third power of the number of equations, there was a need for the development of iterative methods with better performance. In [1] the GMRES algorithm was presented which is now widely used for implementations of the collocation BEM. While the FEM results in sparsely populated coefficient matrices, the BEM leads, in general, to fully or densely populated ones, depending on the number of subregions, posing a serious memory problem even for todays computers. If the geometry of the problem permits the surface of the domain to be meshed with equally shaped elements a lot of the resulting coefficients will be calculated and stored repeatedly. The present paper shows how these unnecessary operations can be avoided reducing the calculation time as well as the storage requirement. To this end a similar coefficient identification algorithm (SCIA), has been developed and implemented in a program written in Fortran 90. The vertical dynamic stiffness of a single pile in layered soil has been chosen to test the performance of the implementation. The results obtained with the 3-d model may be compared with those obtained with an axisymmetric formulation which are considered to be the reference values as the mesh quality is much better. The entire 3D model comprises more than 35000 dofs being a soil region with 21168 dofs the biggest single region. Note that the memory necessary to store all coefficients of this single region is about 6.8 GB, an amount which is usually not available with personal computers. In the problem under study the interface zone between the two adjacent soil regions as well as the surface of the top layer may be meshed with equally sized elements. In this case the application of the SCIA leads to an important reduction in memory requirements. The maximum memory used during the calculation has been reduced to 1.2 GB. The application of the SCIA thus permits problems to be solved on personal computers which otherwise would require much more powerful hardware.

Influencia de la temperatura en la deflexión de firmes flexibles

En esta investigación se ha estudiado el efecto de la variación de la temperatura en la deflexión de firmes flexibles. En primer lugar se han recopilado los criterios existentes de ajuste de la deflexión por efecto de la temperatura. Posteriormente, se ha llevado a cabo un estudio empírico mediante la auscultación de las deflexiones en cinco tramos de carretera con firme flexible y con diferentes espesores de mezclas bituminosas (entre 10 y 30 cm). Las medidas se han efectuado en dos campañas (verano e invierno), tratando de abarcar un amplio rango de temperaturas. En cada campaña, se han llevado a cabo distintas auscultaciones a diferentes temperaturas. Las medidas de cada campaña se han realizado el mismo día. Se han obtenido los coeficientes empíricos de ajuste por temperatura para cada tramo analizado. Además, se ha realizado un estudio teórico mediante la elaboración de diferentes modelos (multicapa elástico lineal, multicapa visco-elástico lineal y elementos finitos) que reproducen la respuesta estructural de los firmes flexibles auscultados. La caracterización mecánica de las mezclas bituminosas se ha realizado mediante ensayos de módulo complejo en laboratorio, a diferentes temperaturas y frecuencias, sobre testigos extraídos en las carreteras estudiadas. Se han calculado los coeficientes teóricos de ajuste por temperatura para cada modelo elaborado y tramo analizado. Finalmente, se ha realizado un estudio comparativo entre los distintos coeficientes de ajuste (existentes, empíricos y teóricos), que ha puesto de manifiesto que, en todos los casos analizados, los coeficientes obtenidos en el modelo de elementos finitos son los que más se aproximan a los coeficientes empíricos (valor de referencia para los tramos analizados). El modelo desarrollado de elementos finitos permite reproducir el comportamiento visco-elástico de las mezclas bituminosas y el carácter dinámico de las cargas aplicadas. Se han utilizado elementos tipo tetraedro isoparamétrico lineal (C3D8R) para el firme y la parte superior del cimiento, mientras que para la parte inferior se han empleado elementos infinitos (CIN3D8). In this research the effect produced by the temperature change on flexible pavements deflection is analysed. First, the existing criteria of deflection adjustment by temperature were collected. Additionally, an empirical analysis was carried out, consisting on deflection tests in five flexible-pavement road sections with different asphalt mix thickness (from 10 to 30 cm). The measures were taken in two seasons (summer and winter) in an effort to register a wide range of temperatures. Different surveys were carried out at different temperatures in each season. The tests of each season were done at the same day. The empirical temperature adjustment factors for every analysed section were obtained. A theoretical study was carried out by developing different models (linear elastic multilayer, linear visco-elastic multilayer and finite elements) that reproduce the structural response of the tested flexible pavements. The mechanical characterization of the asphalt mixes was achieved through laboratory complex-modulus tests at different temperatures and frequencies, using pavement cores from the surveyed roads. The theoretical temperature adjustment factors for each model developed and each section analysed were calculated. Finally, a comparative study among the different adjustment factors (existing, empirical and theoretical) was carried out. It has shown that, in all analysed cases, the factors obtained with the finite elements model are the closest to the empirical factors (reference value for the analysed sections). The finite elements model developed makes it possible to reproduce the visco-elastic behavior of the asphalt mixes and the dynamic nature of the applied loads. Linear isoparametric tetrahedral elements (C3D8R) have been used for the pavement and the subgrade, while infinite elements (CIN3D8) have been used for the foundations.

Some examples of the simultaneous use of closed-form and numerical solutions in shell structural analysis

The computational advantages of the use of different approaches -numerical and analytical ones- to the analysis of different parts of the same shell structure are discussed. Examples of large size problems that can be reduced to those more suitable to be handled by a personal related axisyrometric finite elements, local unaxisymmetric shells, geometric quasi-regular shells, infinite elements and homogenization techniques are described

The elements of the true arithmetic of infinites : In which all the propositions in the arithmetic of infinites invented by Dr. Wallis, relative to the summation of infinite series : and, also, the principles of the doctrine of fluxions are demonstrated to be false : and the nature of infinitesimals is unfolded /

Mode of access: Internet.

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.

A transient three-dimensional heat transfer model of the human body

The objective of this work is to develop an improved model of the human thermal system. The features included are important to solve real problems: 3D heat conduction, the use of elliptical cylinders to adequately approximate body geometry, the careful representation of tissues and important organs, and the flexibility of the computational implementation. Focus is on the passive system, which is composed by 15 cylindrical elements and it includes heat transfer between large arteries and veins. The results of thermal neutrality and transient simulations are in excellent agreement with experimental data, indicating that the model represents adequately the behavior of the human thermal system. (C) 2009 Elsevier Ltd. All rights reserved.

Mouse interleukin-2 receptor alpha gene expression. Delimitation of cis-acting regulatory elements in transgenic mice and by mapping of DNase-I hypersensitive sites.

The alpha chain of the interleukin-2 receptor (IL-2R alpha) is a key regulator of lymphocyte proliferation. To analyze the mechanisms controlling its expression in normal cells, we used the 5'-flanking region (base pairs -2539/+93) of the mouse gene to drive chloramphenicol acetyltransferase expression in four transgenic mouse lines. Constitutive transgene activity was restricted to lymphoid organs. In mature T lymphocytes, transgene and endogenous IL-2R alpha gene expression was stimulated by concanavalin A and up-regulated by IL-2 with very similar kinetics. In thymic T cell precursors, IL-1 and IL-2 cooperatively induced transgene and IL-2R alpha gene expression. These results show that regulation of the endogenous IL-2R alpha gene occurs mainly at the transcriptional level. They demonstrate that cis-acting elements in the 5'-flanking region present in the transgene confer correct tissue specificity and inducible expression in mature T cells and their precursors in response to antigen, IL-1, and IL-2. In a complementary approach, we screened the 5' end of the endogenous IL-2R alpha gene for DNase-I hypersensitive sites. We found three lymphocyte specific DNase-I hypersensitive sites. Two, at -0.05 and -5.3 kilobase pairs, are present in resting T cells. A third site appears at -1.35 kilobase pairs in activated T cells. It co-localizes with IL-2-responsive elements identified by transient transfection experiments.

Pancreatic-specific expression of the glucose transporter type 2 gene: identification of cis-elements and islet-specific trans-acting factors.

A defect in glucose sensing of the pancreatic beta-cells has been observed in several animal models of type II diabetes and has been correlated with a reduced gene expression of the glucose transporter type 2 (Glut2). In a transgenic mouse model, expression of Glut2 antisense RNA in pancreatic beta-cells has recently been shown to be associated with an impaired glucose-induced insulin secretion and the development of diabetes. To identify factors that may be involved in the specific decrease of Glut2 in the beta-cells of the diabetic animal, an attempt was made to localize the cis-elements and trans-acting factors involved in the control of Glut2 expression in the endocrine pancreas. It was demonstrated by transient transfection studies that only 338 base pairs (bp) of the murine Glut2 proximal promoter are needed for reporter gene expression in pancreatic islet-derived cell lines, whereas no activity was detected in nonpancreatic cells. Three cis-elements, GTI, GTII, and GTIII, have been identified by DNAse I footprinting and gel retardation experiments within these 338 bp. GTI and GTIII bind distinct but ubiquitously expressed trans-acting factors. On the other hand, nuclear proteins specifically expressed in pancreatic cell lines interact with GTII, and their relative abundance correlates with endogenous Glut2 expression. These GTII-binding factors correspond to nuclear proteins of 180 and 90 kilodaltons as defined by Southwestern analysis. The 180-kilodalton factor is present in pancreatic beta-cell lines but not in an alpha-cell line. Mutation of the GTI or GTIII cis-elements decreases transcriptional activity directed by the 338-bp promoter, whereas mutation of GTII increases gene transcription. Thus negative and positive regulatory sequences are identified within the proximal 338 bp of the GLUT2 promoter and may participate in the islet-specific expression of the gene by binding beta-cell specific trans-acting factors.

Use of human MAR elements to improve retroviral vector production.

Retroviral vectors have many favorable properties for gene therapies, but their use remains limited by safety concerns and/or by relatively lower titers for some of the safer self-inactivating (SIN) derivatives. In this study, we evaluated whether increased production of SIN retroviral vectors can be achieved from the use of matrix attachment region (MAR) epigenetic regulators. Two MAR elements of human origin were found to increase and to stabilize the expression of the green fluorescent protein transgene in stably transfected HEK-293 packaging cells. Introduction of one of these MAR elements in retroviral vector-producing plasmids yielded higher expression of the viral vector RNA. Consistently, viral titers obtained from transient transfection of MAR-containing plasmids were increased up to sixfold as compared with the parental construct, when evaluated in different packaging cell systems and transfection conditions. Thus, use of MAR elements opens new perspectives for the efficient generation of gene therapy vectors.

Identification of a potent MAR element from the mouse genome and assessment of its activity in stable and transient transfections.

Matrix attachment regions are DNA sequences found throughout eukaryotic genomes that are believed to define boundaries interfacing heterochromatin and euchromatin domains, thereby acting as epigenetic regulators. When included in expression vectors, MARs can improve and sustain transgene expression, and a search for more potent novel elements is therefore actively pursued to further improve recombinant protein production. Here we describe the isolation of new MARs from the mouse genome using a modified in silico analysis. One of these MARs was found to be a powerful activator of transgene expression in stable transfections. Interestingly, this MAR also increased GFP and/or immunoglobulin expression from some but not all expression vectors in transient transfections. This effect was attributed to the presence or absence of elements on the vector backbone, providing an explanation for earlier discrepancies as to the ability of this class of elements to affect transgene expression under such conditions.

Roles of transient guidepost neurons in corpus callosum formation and guidance

RESUMENeurones transitoires jouant un rôle de cibles intermédiaires dans le guidage des axones du corps calleuxLe guidage axonal est une étape clé permettant aux neurones d'établir des connexions synaptiques et de s'intégrer dans un réseau neural fonctionnel de manière spécifique. Des cellules-cibles intermédiaires appelées « guidepost » aident les axones à parcourir de longues distances dans le cerveau en leur fournissant des informations directionnelles tout au long de leur trajet. Il a été démontré que des sous-populations de cellules gliales au niveau de la ligne médiane guident les axones du corps calleux (CC) d'un hémisphère vers l'autre. Bien qu'il fût observé que le CC en développement contenait aussi des neurones, leur rôle était resté jusqu'alors inconnu.La publication de nos résultats a montré que pendant le développement embryonnaire, le CC contient des glies mais aussi un nombre considérable de neurones glutamatergiques et GABAergiques, nécessaires à la formation du corps calleux (Niquille et al., PLoS Biology, 2009). Dans ce travail, j'ai utilisé des techniques de morphologie et d'imagerie confocale 3D pour définir le cadre neuro-anatomique de notre modèle. De plus, à l'aide de transplantations sur tranches in vitro, de co-explants, d'expression de siRNA dans des cultures de neurones primaires et d'analyse in vivo sur des souris knock-out, nous avons démontré que les neurones du CC guident les axones callosaux en partie grâce à l'action attractive du facteur de guidage Sema3C sur son récepteur Npn- 1.Récemment, nous avons étudié l'origine, les aspects dynamiques de ces processus, ainsi que les mécanismes moléculaires impliqués dans la mise en place de ce faisceau axonal (Niquille et al., soumis). Tout d'abord, nous avons précisé l'origine et l'identité des neurones guidepost GABAergiques du CC par une étude approfondie de traçage génétique in vivo. J'ai identifié, dans le CC, deux populations distinctes de neurones GABAergiques venant des éminences ganglionnaires médiane (MGE) et caudale (CGE). J'ai ensuite étudié plus en détail les interactions dynamiques entre neurones et axones du corps calleux par microscopie confocale en temps réel. Puis nous avons défini le rôle de chaque sous-population neuronale dans le guidage des axones callosaux et de manière intéressante les neurones GABAergic dérivés de la MGE comme ceux de la CGE se sont révélés avoir une action attractive pour les axones callosaux dans des expériences de transplantation. Enfin, nous avons clarifié la base moléculaire de ces mécanismes de guidage par FACS sorting associé à un large criblage génétique de molécules d'intérêt par une technique très sensible de RT-PCR et ensuite ces résultats ont été validés par hybridation in situ.Nous avons également étudié si les neurones guidepost du CC étaient impliqués dans son agénésie (absence de CC), présente dans nombreux syndromes congénitaux chez 1 humain. Le gène homéotique Aristaless (Arx) contrôle la migration des neurones GABAergiques et sa mutation conduit à de nombreuses pathologies humaines, notamment la lissencéphalie liée à IX avec organes génitaux anormaux (XLAG) et agénésie du CC. Fait intéressant, nous avons constaté qu'ARX est exprimé dans toutes les populations GABAergiques guidepost du CC et que les embryons mutant pour Arx présentent une perte drastique de ces neurones accompagnée de défauts de navigation des axones (Niquille et al., en préparation). En outre, nous avons découvert que les souris déficientes pour le facteur de transcription ciliogenic RFX3 souffrent d'une agénésie du CC associé avec des défauts de mise en place de la ligne médiane et une désorganisation secondaire des neurones glutamatergiques guidepost (Benadiba et al., submitted). Ceci suggère fortement l'implication potentielle des deux types de neurones guidepost dans l'agénésie du CC chez l'humain.Ainsi, mon travail de thèse révèle de nouvelles fonctions pour ces neurones transitoires dans le guidage axonal et apporte de nouvelles perspectives sur les rôles respectifs des cellules neuronales et gliales dans ce processus.ABSTRACTRole of transient guidepost neurons in corpus callosum development and guidanceAxonal guidance is a key step that allows neurons to build specific synaptic connections and to specifically integrate in a functional neural network. Intermediate targets or guidepost cells act as critical elements that help to guide axons through long distance in the brain and provide information all along their travel. Subpopulations of midline glial cells have been shown to guide corpus callosum (CC) axons to the contralateral cerebral hemisphere. While neuronal cells are also present in the developing corpus callosum, their role still remains elusive.Our published results unravelled that, during embryonic development, the CC is populated in addition to astroglia by numerous glutamatergic and GABAergic guidepost neurons that are essential for the correct midline crossing of callosal axons (Niquille et al., PLoS Biology, 2009). In this work, I have combined morphological and 3D confocal imaging techniques to define the neuro- anatomical frame of our system. Moreover, with the use of in vitro transplantations in slices, co- explant experiments, siRNA manipulations on primary neuronal culture and in vivo analysis of knock-out mice we have been able to demonstrate that CC neurons direct callosal axon outgrowth, in part through the attractive action of Sema3C on its Npn-1 receptor.Recently, we have studied the origin, the dynamic aspects of these processes as well as the molecular mechanisms involved in the establishment of this axonal tract (Niquille et al., submitted). First, we have clarified the origin and the identity of the CC GABAergic guidepost neurons using extensive in vivo cell fate-mapping experiments. We identified two distinct GABAergic neuronal subpopulations, originating from the medial (MGE) and caudal (CGE) ganglionic eminences. I then studied in more details the dynamic interactions between CC neurons and callosal axons by confocal time-lapse video microscopy and I have also further characterized the role of each guidepost neuronal subpopulation in callosal guidance. Interestingly, MGE- and CGE-derived GABAergic neurons are both attractive for callosal axons in transplantation experiments. Finally, we have dissected the molecular basis of these guidance mechanisms by using FACS sorting combined with an extensive genetic screen for molecules of interest by a sensitive RT-PCR technique, as well as, in situ hybridization.I have also investigated whether CC guidepost neurons are involved in agenesis of the CC which occurs in numerous human congenital syndromes. Aristaless-related homeobox gene (Arx) regulates GABAergic neuron migration and its mutation leads to numerous human pathologies including X-linked lissencephaly with abnormal genitalia (XLAG) and severe CC agenesis. Interestingly, I found that ARX is expressed in all the guidepost GABAergic neuronal populations of the CC and that Arx-/- embryos exhibit a drastic loss of CC GABAergic interneurons accompanied by callosal axon navigation defects (Niquille et al, in preparation). In addition, we discovered that mice deficient for the ciliogenic transcription factor RFX3 suffer from CC agenesis associated with early midline patterning defects and a secondary disorganisation of guidepost glutamatergic neurons (Benadiba et al., submitted). This strongly points out the potential implication of both types of guidepost neurons in human CC agenesis.Taken together, my thesis work reveals novel functions for transient neurons in axonal guidance and brings new perspectives on the respective roles of neuronal and glial cells in these processes.