STATISTICAL METHODS FOR RARE AND COMMON VARIANT ASSOCIATION STUDIES

Complex human diseases are a major challenge for biological research. The goal of my research is to develop effective methods for biostatistics in order to create more opportunities for the prevention and cure of human diseases. This dissertation proposes statistical technologies that have the ability of being adapted to sequencing data in family-based designs, and that account for joint effects as well as gene-gene and gene-environment interactions in the GWA studies. The framework includes statistical methods for rare and common variant association studies. Although next-generation DNA sequencing technologies have made rare variant association studies feasible, the development of powerful statistical methods for rare variant association studies is still underway. Chapter 2 demonstrates two adaptive weighting methods for rare variant association studies based on family data for quantitative traits. The results show that both proposed methods are robust to population stratification, robust to the direction and magnitude of the effects of causal variants, and more powerful than the methods using weights suggested by Madsen and Browning [2009]. In Chapter 3, I extended the previously proposed test for Testing the effect of an Optimally Weighted combination of variants (TOW) [Sha et al., 2012] for unrelated individuals to TOW &ndash F, TOW for Family &ndash based design. Simulation results show that TOW &ndash F can control for population stratification in wide range of population structures including spatially structured populations, is robust to the directions of effect of causal variants, and is relatively robust to percentage of neutral variants. In GWA studies, this dissertation consists of a two &ndash locus joint effect analysis and a two-stage approach accounting for gene &ndash gene and gene &ndash environment interaction. Chapter 4 proposes a novel two &ndash stage approach, which is promising to identify joint effects, especially for monotonic models. The proposed approach outperforms a single &ndash marker method and a regular two &ndash stage analysis based on the two &ndash locus genotypic test. In Chapter 5, I proposed a gene &ndash based two &ndash stage approach to identify gene &ndash gene and gene &ndash environment interactions in GWA studies which can include rare variants. The two &ndash stage approach is applied to the GAW 17 dataset to identify the interaction between KDR gene and smoking status.

Age modeling of young non-varved lake sediments: methods and limits. Examples from two lakes in Central Chile

High-resolution and highly precise age models for recent lake sediments (last 100–150 years) are essential for quantitative paleoclimate research. These are particularly important for sedimentological and geochemical proxies, where transfer functions cannot be established and calibration must be based upon the relation of sedimentary records to instrumental data. High-precision dating for the calibration period is most critical as it determines directly the quality of the calibration statistics. Here, as an example, we compare radionuclide age models obtained on two high-elevation glacial lakes in the Central Chilean Andes (Laguna Negra: 33°38′S/70°08′W, 2,680 m a.s.l. and Laguna El Ocho: 34°02′S/70°19′W, 3,250 m a.s.l.). We show the different numerical models that produce accurate age-depth chronologies based on 210Pb profiles, and we explain how to obtain reduced age-error bars at the bottom part of the profiles, i.e., typically around the end of the 19th century. In order to constrain the age models, we propose a method with five steps: (i) sampling at irregularly-spaced intervals for 226Ra, 210Pb and 137Cs depending on the stratigraphy and microfacies, (ii) a systematic comparison of numerical models for the calculation of 210Pb-based age models: constant flux constant sedimentation (CFCS), constant initial concentration (CIC), constant rate of supply (CRS) and sediment isotope tomography (SIT), (iii) numerical constraining of the CRS and SIT models with the 137Cs chronomarker of AD 1964 and, (iv) step-wise cross-validation with independent diagnostic environmental stratigraphic markers of known age (e.g., volcanic ash layer, historical flood and earthquakes). In both examples, we also use airborne pollutants such as spheroidal carbonaceous particles (reflecting the history of fossil fuel emissions), excess atmospheric Cu deposition (reflecting the production history of a large local Cu mine), and turbidites related to historical earthquakes. Our results show that the SIT model constrained with the 137Cs AD 1964 peak performs best over the entire chronological profile (last 100–150 years) and yields the smallest standard deviations for the sediment ages. Such precision is critical for the calibration statistics, and ultimately, for the quality of the quantitative paleoclimate reconstruction. The systematic comparison of CRS and SIT models also helps to validate the robustness of the chronologies in different sections of the profile. Although surprisingly poorly known and under-explored in paleolimnological research, the SIT model has a great potential in paleoclimatological reconstructions based on lake sediments

Combining Monte Carlo methods with coherent wave optics for the simulation of phase-sensitive X-ray imaging

Phase-sensitive X-ray imaging shows a high sensitivity towards electron density variations, making it well suited for imaging of soft tissue matter. However, there are still open questions about the details of the image formation process. Here, a framework for numerical simulations of phase-sensitive X-ray imaging is presented, which takes both particle- and wave-like properties of X-rays into consideration. A split approach is presented where we combine a Monte Carlo method (MC) based sample part with a wave optics simulation based propagation part, leading to a framework that takes both particle- and wave-like properties into account. The framework can be adapted to different phase-sensitive imaging methods and has been validated through comparisons with experiments for grating interferometry and propagation-based imaging. The validation of the framework shows that the combination of wave optics and MC has been successfully implemented and yields good agreement between measurements and simulations. This demonstrates that the physical processes relevant for developing a deeper understanding of scattering in the context of phase-sensitive imaging are modelled in a sufficiently accurate manner. The framework can be used for the simulation of phase-sensitive X-ray imaging, for instance for the simulation of grating interferometry or propagation-based imaging.

The Utilization of Classical Spin Monte Carlo Methods to Simulate the Magnetic Behavior of Extended Three-Dimensional Cubic Networks Incorporating M(II) Ions with an S = 5/2 Ground State Spin

The numerical simulations of the magnetic properties of extended three-dimensional networks containing M(II) ions with an S = 5/2 ground-state spin have been carried out within the framework of the isotropic Heisenberg model. Analytical expressions fitting the numerical simulations for the primitive cubic, diamond, together with (10−3) cubic networks have all been derived. With these empirical formulas in hands, we can now extract the interaction between the magnetic ions from the experimental data for these networks. In the case of the primitive cubic network, these expressions are directly compared with those from the high-temperature expansions of the partition function. A fit of the experimental data for three complexes, namely [(N(CH3)4][Mn(N3)] 1, [Mn(CN4)]n 2, and [FeII(bipy)3][MnII2(ox)3] 3, has been carried out. The best fits were those obtained using the following parameters, J = −3.5 cm-1, g = 2.01 (1); J = −8.3 cm-1, g = 1.95 (2); and J = −2.0 cm-1, g = 1.95 (3).

Fully Adaptive Newton--Galerkin Methods for Semilinear Elliptic Partial Differential Equations

In this paper we develop an adaptive procedure for the numerical solution of general, semilinear elliptic problems with possible singular perturbations. Our approach combines both prediction-type adaptive Newton methods and a linear adaptive finite element discretization (based on a robust a posteriori error analysis), thereby leading to a fully adaptive Newton–Galerkin scheme. Numerical experiments underline the robustness and reliability of the proposed approach for various examples

Computational Comparison of Continuous and Discontinuous Galerkin Time-Stepping Methods for Nonlinear Initial Value Problems

This article centers on the computational performance of the continuous and discontinuous Galerkin time stepping schemes for general first-order initial value problems in R n , with continuous nonlinearities. We briefly review a recent existence result for discrete solutions from [6], and provide a numerical comparison of the two time discretization methods.

Comparison of multiple comparison methods for identifying differential gene expression in simulated and real papillary thyroid cancer microarray data

The difficulty of detecting differential gene expression in microarray data has existed for many years. Several correction procedures try to avoid the family-wise error rate in multiple comparison process, including the Bonferroni and Sidak single-step p-value adjustments, Holm's step-down correction method, and Benjamini and Hochberg's false discovery rate (FDR) correction procedure. Each multiple comparison technique has its advantages and weaknesses. We studied each multiple comparison method through numerical studies (simulations) and applied the methods to the real exploratory DNA microarray data, which detect of molecular signatures in papillary thyroid cancer (PTC) patients. According to our results of simulation studies, Benjamini and Hochberg step-up FDR controlling procedure is the best process among these multiple comparison methods and we discovered 1277 potential biomarkers among 54675 probe sets after applying the Benjamini and Hochberg's method to PTC microarray data.^

A robust numerical framework for the analysis of material failure of fibre reinforced soft tissue

In this work, robustness and stability of continuum damage models applied to material failure in soft tissues are addressed. In the implicit damage models equipped with softening, the presence of negative eigenvalues in the tangent elemental matrix degrades the condition number of the global matrix, leading to a reduction of the computational performance of the numerical model. Two strategies have been adapted from literature to improve the aforementioned computational performance degradation: the IMPL-EX integration scheme [Oliver,2006], which renders the elemental matrix contribution definite positive, and arclength-type continuation methods [Carrera,1994], which allow to capture the unstable softening branch in brittle ruptures. The IMPL-EX integration scheme has as a major drawback the need to use small time steps to keep numerical error below an acceptable value. A convergence study, limiting the maximum allowed increment of internal variables in the damage model, is presented. Finally, numerical simulation of failure problems with fibre reinforced materials illustrates the performance of the adopted methodology.

Categorical Missing Data Imputation Using Fuzzy Neural Networks with Numerical and Categorical Inputs

There are many situations where input feature vectors are incomplete and methods to tackle the problem have been studied for a long time. A commonly used procedure is to replace each missing value with an imputation. This paper presents a method to perform categorical missing data imputation from numerical and categorical variables. The imputations are based on Simpson’s fuzzy min-max neural networks where the input variables for learning and classification are just numerical. The proposed method extends the input to categorical variables by introducing new fuzzy sets, a new operation and a new architecture. The procedure is tested and compared with others using opinion poll data.

Numerical Error Prediction and its applications in CFD using tau-estimation

Nowadays, Computational Fluid Dynamics (CFD) solvers are widely used within the industry to model fluid flow phenomenons. Several fluid flow model equations have been employed in the last decades to simulate and predict forces acting, for example, on different aircraft configurations. Computational time and accuracy are strongly dependent on the fluid flow model equation and the spatial dimension of the problem considered. While simple models based on perfect flows, like panel methods or potential flow models can be very fast to solve, they usually suffer from a poor accuracy in order to simulate real flows (transonic, viscous). On the other hand, more complex models such as the full Navier- Stokes equations provide high fidelity predictions but at a much higher computational cost. Thus, a good compromise between accuracy and computational time has to be fixed for engineering applications. A discretisation technique widely used within the industry is the so-called Finite Volume approach on unstructured meshes. This technique spatially discretises the flow motion equations onto a set of elements which form a mesh, a discrete representation of the continuous domain. Using this approach, for a given flow model equation, the accuracy and computational time mainly depend on the distribution of nodes forming the mesh. Therefore, a good compromise between accuracy and computational time might be obtained by carefully defining the mesh. However, defining an optimal mesh for complex flows and geometries requires a very high level expertize in fluid mechanics and numerical analysis, and in most cases a simple guess of regions of the computational domain which might affect the most the accuracy is impossible. Thus, it is desirable to have an automatized remeshing tool, which is more flexible with unstructured meshes than its structured counterpart. However, adaptive methods currently in use still have an opened question: how to efficiently drive the adaptation ? Pioneering sensors based on flow features generally suffer from a lack of reliability, so in the last decade more effort has been made in developing numerical error-based sensors, like for instance the adjoint-based adaptation sensors. While very efficient at adapting meshes for a given functional output, the latter method is very expensive as it requires to solve a dual set of equations and computes the sensor on an embedded mesh. Therefore, it would be desirable to develop a more affordable numerical error estimation method. The current work aims at estimating the truncation error, which arises when discretising a partial differential equation. These are the higher order terms neglected in the construction of the numerical scheme. The truncation error provides very useful information as it is strongly related to the flow model equation and its discretisation. On one hand, it is a very reliable measure of the quality of the mesh, therefore very useful in order to drive a mesh adaptation procedure. On the other hand, it is strongly linked to the flow model equation, so that a careful estimation actually gives information on how well a given equation is solved, which may be useful in the context of _ -extrapolation or zonal modelling. The following work is organized as follows: Chap. 1 contains a short review of mesh adaptation techniques as well as numerical error prediction. In the first section, Sec. 1.1, the basic refinement strategies are reviewed and the main contribution to structured and unstructured mesh adaptation are presented. Sec. 1.2 introduces the definitions of errors encountered when solving Computational Fluid Dynamics problems and reviews the most common approaches to predict them. Chap. 2 is devoted to the mathematical formulation of truncation error estimation in the context of finite volume methodology, as well as a complete verification procedure. Several features are studied, such as the influence of grid non-uniformities, non-linearity, boundary conditions and non-converged numerical solutions. This verification part has been submitted and accepted for publication in the Journal of Computational Physics. Chap. 3 presents a mesh adaptation algorithm based on truncation error estimates and compares the results to a feature-based and an adjoint-based sensor (in collaboration with Jorge Ponsín, INTA). Two- and three-dimensional cases relevant for validation in the aeronautical industry are considered. This part has been submitted and accepted in the AIAA Journal. An extension to Reynolds Averaged Navier- Stokes equations is also included, where _ -estimation-based mesh adaptation and _ -extrapolation are applied to viscous wing profiles. The latter has been submitted in the Proceedings of the Institution of Mechanical Engineers, Part G: Journal of Aerospace Engineering. Keywords: mesh adaptation, numerical error prediction, finite volume Hoy en día, la Dinámica de Fluidos Computacional (CFD) es ampliamente utilizada dentro de la industria para obtener información sobre fenómenos fluidos. La Dinámica de Fluidos Computacional considera distintas modelizaciones de las ecuaciones fluidas (Potencial, Euler, Navier-Stokes, etc) para simular y predecir las fuerzas que actúan, por ejemplo, sobre una configuración de aeronave. El tiempo de cálculo y la precisión en la solución depende en gran medida de los modelos utilizados, así como de la dimensión espacial del problema considerado. Mientras que modelos simples basados en flujos perfectos, como modelos de flujos potenciales, se pueden resolver rápidamente, por lo general aducen de una baja precisión a la hora de simular flujos reales (viscosos, transónicos, etc). Por otro lado, modelos más complejos tales como el conjunto de ecuaciones de Navier-Stokes proporcionan predicciones de alta fidelidad, a expensas de un coste computacional mucho más elevado. Por lo tanto, en términos de aplicaciones de ingeniería se debe fijar un buen compromiso entre precisión y tiempo de cálculo. Una técnica de discretización ampliamente utilizada en la industria es el método de los Volúmenes Finitos en mallas no estructuradas. Esta técnica discretiza espacialmente las ecuaciones del movimiento del flujo sobre un conjunto de elementos que forman una malla, una representación discreta del dominio continuo. Utilizando este enfoque, para una ecuación de flujo dado, la precisión y el tiempo computacional dependen principalmente de la distribución de los nodos que forman la malla. Por consiguiente, un buen compromiso entre precisión y tiempo de cálculo se podría obtener definiendo cuidadosamente la malla, concentrando sus elementos en aquellas zonas donde sea estrictamente necesario. Sin embargo, la definición de una malla óptima para corrientes y geometrías complejas requiere un nivel muy alto de experiencia en la mecánica de fluidos y el análisis numérico, así como un conocimiento previo de la solución. Aspecto que en la mayoría de los casos no está disponible. Por tanto, es deseable tener una herramienta que permita adaptar los elementos de malla de forma automática, acorde a la solución fluida (remallado). Esta herramienta es generalmente más flexible en mallas no estructuradas que con su homóloga estructurada. No obstante, los métodos de adaptación actualmente en uso todavía dejan una pregunta abierta: cómo conducir de manera eficiente la adaptación. Sensores pioneros basados en las características del flujo en general, adolecen de una falta de fiabilidad, por lo que en la última década se han realizado grandes esfuerzos en el desarrollo numérico de sensores basados en el error, como por ejemplo los sensores basados en el adjunto. A pesar de ser muy eficientes en la adaptación de mallas para un determinado funcional, este último método resulta muy costoso, pues requiere resolver un doble conjunto de ecuaciones: la solución y su adjunta. Por tanto, es deseable desarrollar un método numérico de estimación de error más asequible. El presente trabajo tiene como objetivo estimar el error local de truncación, que aparece cuando se discretiza una ecuación en derivadas parciales. Estos son los términos de orden superior olvidados en la construcción del esquema numérico. El error de truncación proporciona una información muy útil sobre la solución: es una medida muy fiable de la calidad de la malla, obteniendo información que permite llevar a cabo un procedimiento de adaptación de malla. Está fuertemente relacionado al modelo matemático fluido, de modo que una estimación precisa garantiza la idoneidad de dicho modelo en un campo fluido, lo que puede ser útil en el contexto de modelado zonal. Por último, permite mejorar la precisión de la solución resolviendo un nuevo sistema donde el error local actúa como término fuente (_ -extrapolación). El presenta trabajo se organiza de la siguiente manera: Cap. 1 contiene una breve reseña de las técnicas de adaptación de malla, así como de los métodos de predicción de los errores numéricos. En la primera sección, Sec. 1.1, se examinan las estrategias básicas de refinamiento y se presenta la principal contribución a la adaptación de malla estructurada y no estructurada. Sec 1.2 introduce las definiciones de los errores encontrados en la resolución de problemas de Dinámica Computacional de Fluidos y se examinan los enfoques más comunes para predecirlos. Cap. 2 está dedicado a la formulación matemática de la estimación del error de truncación en el contexto de la metodología de Volúmenes Finitos, así como a un procedimiento de verificación completo. Se estudian varias características que influyen en su estimación: la influencia de la falta de uniformidad de la malla, el efecto de las no linealidades del modelo matemático, diferentes condiciones de contorno y soluciones numéricas no convergidas. Esta parte de verificación ha sido presentada y aceptada para su publicación en el Journal of Computational Physics. Cap. 3 presenta un algoritmo de adaptación de malla basado en la estimación del error de truncación y compara los resultados con sensores de featured-based y adjointbased (en colaboración con Jorge Ponsín del INTA). Se consideran casos en dos y tres dimensiones, relevantes para la validación en la industria aeronáutica. Este trabajo ha sido presentado y aceptado en el AIAA Journal. También se incluye una extensión de estos métodos a las ecuaciones RANS (Reynolds Average Navier- Stokes), en donde adaptación de malla basada en _ y _ -extrapolación son aplicados a perfiles con viscosidad de alas. Este último trabajo se ha presentado en los Actas de la Institución de Ingenieros Mecánicos, Parte G: Journal of Aerospace Engineering. Palabras clave: adaptación de malla, predicción del error numérico, volúmenes finitos

A comparison among different spectrum compatible earthquake simulation methods

The need for the simulation of spectrum compatible earthquake time histories has existed since earthquake engineering for complicated structures began. More than the safety of the main structure, the analysis of the equipment (piping, racks, etc.) can only be assessed on the basis of the time history of the floor in which they are contained. This paper presents several methods for calculating simulated spectrum compatible earthquakes as well as a comparison between them. As a result of this comparison, the use of the phase content in real earthquakes as proposed by Ohsaki appears as an effective alternative to the classical methods. With this method, it is possible to establish an approach without the arbitrary modulation commonly used in other methods. Different procedures are described as is the influence of the different parameters which appear in the analysis. Several numerical examples are also presented, and the effectiveness of Ohsaki's method is confirmed.

Elastoplastic consolidation at finite strain. Part 2: finite element implementation and numerical examples

A mathematical model for finite strain elastoplastic consolidation of fully saturated soil media is implemented into a finite element program. The algorithmic treatment of finite strain elastoplasticity for the solid phase is based on multiplicative decomposition and is coupled with the algorithm for fluid flow via the Kirchhoff pore water pressure. A two-field mixed finite element formulation is employed in which the nodal solid displacements and the nodal pore water pressures are coupled via the linear momentum and mass balance equations. The constitutive model for the solid phase is represented by modified Cam—Clay theory formulated in the Kirchhoff principal stress space, and return mapping is carried out in the strain space defined by the invariants of the elastic logarithmic principal stretches. The constitutive model for fluid flow is represented by a generalized Darcy's law formulated with respect to the current configuration. The finite element model is fully amenable to exact linearization. Numerical examples with and without finite deformation effects are presented to demonstrate the impact of geometric nonlinearity on the predicted responses. The paper concludes with an assessment of the performance of the finite element consolidation model with respect to accuracy and numerical stability.

Column Generation Algorithms for Nonlinear Optimization II: Numerical Investigations

García et al. present a class of column generation (CG) algorithms for nonlinear programs. Its main motivation from a theoretical viewpoint is that under some circumstances, finite convergence can be achieved, in much the same way as for the classic simplicial decomposition method; the main practical motivation is that within the class there are certain nonlinear column generation problems that can accelerate the convergence of a solution approach which generates a sequence of feasible points. This algorithm can, for example, accelerate simplicial decomposition schemes by making the subproblems nonlinear. This paper complements the theoretical study on the asymptotic and finite convergence of these methods given in [1] with an experimental study focused on their computational efficiency. Three types of numerical experiments are conducted. The first group of test problems has been designed to study the parameters involved in these methods. The second group has been designed to investigate the role and the computation of the prolongation of the generated columns to the relative boundary. The last one has been designed to carry out a more complete investigation of the difference in computational efficiency between linear and nonlinear column generation approaches. In order to carry out this investigation, we consider two types of test problems: the first one is the nonlinear, capacitated single-commodity network flow problem of which several large-scale instances with varied degrees of nonlinearity and total capacity are constructed and investigated, and the second one is a combined traffic assignment model

Experimental and numerical analysis of reinforced concrete elements subjected to blast loading

El hormigón es uno de los materiales de construcción más empleados en la actualidad debido a sus buenas prestaciones mecánicas, moldeabilidad y economía de obtención, entre otras ventajas. Es bien sabido que tiene una buena resistencia a compresión y una baja resistencia a tracción, por lo que se arma con barras de acero para formar el hormigón armado, material que se ha convertido por méritos propios en la solución constructiva más importante de nuestra época. A pesar de ser un material profusamente utilizado, hay aspectos del comportamiento del hormigón que todavía no son completamente conocidos, como es el caso de su respuesta ante los efectos de una explosión. Este es un campo de especial relevancia, debido a que los eventos, tanto intencionados como accidentales, en los que una estructura se ve sometida a una explosión son, por desgracia, relativamente frecuentes. La solicitación de una estructura ante una explosión se produce por el impacto sobre la misma de la onda de presión generada en la detonación. La aplicación de esta carga sobre la estructura es muy rápida y de muy corta duración. Este tipo de acciones se denominan cargas impulsivas, y pueden ser hasta cuatro órdenes de magnitud más rápidas que las cargas dinámicas impuestas por un terremoto. En consecuencia, no es de extrañar que sus efectos sobre las estructuras y sus materiales sean muy distintos que las que producen las cargas habitualmente consideradas en ingeniería. En la presente tesis doctoral se profundiza en el conocimiento del comportamiento material del hormigón sometido a explosiones. Para ello, es crucial contar con resultados experimentales de estructuras de hormigón sometidas a explosiones. Este tipo de resultados es difícil de encontrar en la literatura científica, ya que estos ensayos han sido tradicionalmente llevados a cabo en el ámbito militar y los resultados obtenidos no son de dominio público. Por otra parte, en las campañas experimentales con explosiones llevadas a cabo por instituciones civiles el elevado coste de acceso a explosivos y a campos de prueba adecuados no permite la realización de ensayos con un elevado número de muestras. Por este motivo, la dispersión experimental no es habitualmente controlada. Sin embargo, en elementos de hormigón armado sometidos a explosiones, la dispersión experimental es muy acusada, en primer lugar, por la propia heterogeneidad del hormigón, y en segundo, por la dificultad inherente a la realización de ensayos con explosiones, por motivos tales como dificultades en las condiciones de contorno, variabilidad del explosivo, o incluso cambios en las condiciones atmosféricas. Para paliar estos inconvenientes, en esta tesis doctoral se ha diseñado un novedoso dispositivo que permite ensayar hasta cuatro losas de hormigón bajo la misma detonación, lo que además de proporcionar un número de muestras estadísticamente representativo, supone un importante ahorro de costes. Con este dispositivo se han ensayado 28 losas de hormigón, tanto armadas como en masa, de dos dosificaciones distintas. Pero además de contar con datos experimentales, también es importante disponer de herramientas de cálculo para el análisis y diseño de estructuras sometidas a explosiones. Aunque existen diversos métodos analíticos, hoy por hoy las técnicas de simulación numérica suponen la alternativa más avanzada y versátil para el cálculo de elementos estructurales sometidos a cargas impulsivas. Sin embargo, para obtener resultados fiables es crucial contar con modelos constitutivos de material que tengan en cuenta los parámetros que gobiernan el comportamiento para el caso de carga en estudio. En este sentido, cabe destacar que la mayoría de los modelos constitutivos desarrollados para el hormigón a altas velocidades de deformación proceden del ámbito balístico, donde dominan las grandes tensiones de compresión en el entorno local de la zona afectada por el impacto. En el caso de los elementos de hormigón sometidos a explosiones, las tensiones de compresión son mucho más moderadas, siendo las tensiones de tracción generalmente las causantes de la rotura del material. En esta tesis doctoral se analiza la validez de algunos de los modelos disponibles, confirmando que los parámetros que gobiernan el fallo de las losas de hormigón armado ante explosiones son la resistencia a tracción y su ablandamiento tras rotura. En base a los resultados anteriores se ha desarrollado un modelo constitutivo para el hormigón ante altas velocidades de deformación, que sólo tiene en cuenta la rotura por tracción. Este modelo parte del de fisura cohesiva embebida con discontinuidad fuerte, desarrollado por Planas y Sancho, que ha demostrado su capacidad en la predicción de la rotura a tracción de elementos de hormigón en masa. El modelo ha sido modificado para su implementación en el programa comercial de integración explícita LS-DYNA, utilizando elementos finitos hexaédricos e incorporando la dependencia de la velocidad de deformación para permitir su utilización en el ámbito dinámico. El modelo es estrictamente local y no requiere de remallado ni conocer previamente la trayectoria de la fisura. Este modelo constitutivo ha sido utilizado para simular dos campañas experimentales, probando la hipótesis de que el fallo de elementos de hormigón ante explosiones está gobernado por el comportamiento a tracción, siendo de especial relevancia el ablandamiento del hormigón. Concrete is nowadays one of the most widely used building materials because of its good mechanical properties, moldability and production economy, among other advantages. As it is known, it has high compressive and low tensile strengths and for this reason it is reinforced with steel bars to form reinforced concrete, a material that has become the most important constructive solution of our time. Despite being such a widely used material, there are some aspects of concrete performance that are not yet fully understood, as it is the case of its response to the effects of an explosion. This is a topic of particular relevance because the events, both intentional and accidental, in which a structure is subjected to an explosion are, unfortunately, relatively common. The loading of a structure due to an explosive event occurs due to the impact of the pressure shock wave generated in the detonation. The application of this load on the structure is very fast and of very short duration. Such actions are called impulsive loads, and can be up to four orders of magnitude faster than the dynamic loads imposed by an earthquake. Consequently, it is not surprising that their effects on structures and materials are very different than those that cause the loads usually considered in engineering. This thesis broadens the knowledge about the material behavior of concrete subjected to explosions. To that end, it is crucial to have experimental results of concrete structures subjected to explosions. These types of results are difficult to find in the scientific literature, as these tests have traditionally been carried out by armies of different countries and the results obtained are classified. Moreover, in experimental campaigns with explosives conducted by civil institutions the high cost of accessing explosives and the lack of proper test fields does not allow for the testing of a large number of samples. For this reason, the experimental scatter is usually not controlled. However, in reinforced concrete elements subjected to explosions the experimental dispersion is very pronounced. First, due to the heterogeneity of concrete, and secondly, because of the difficulty inherent to testing with explosions, for reasons such as difficulties in the boundary conditions, variability of the explosive, or even atmospheric changes. To overcome these drawbacks, in this thesis we have designed a novel device that allows for testing up to four concrete slabs under the same detonation, which apart from providing a statistically representative number of samples, represents a significant saving in costs. A number of 28 slabs were tested using this device. The slabs were both reinforced and plain concrete, and two different concrete mixes were used. Besides having experimental data, it is also important to have computational tools for the analysis and design of structures subjected to explosions. Despite the existence of several analytical methods, numerical simulation techniques nowadays represent the most advanced and versatile alternative for the assessment of structural elements subjected to impulsive loading. However, to obtain reliable results it is crucial to have material constitutive models that take into account the parameters that govern the behavior for the load case under study. In this regard it is noteworthy that most of the developed constitutive models for concrete at high strain rates arise from the ballistic field, dominated by large compressive stresses in the local environment of the area affected by the impact. In the case of concrete elements subjected to an explosion, the compressive stresses are much more moderate, while tensile stresses usually cause material failure. This thesis discusses the validity of some of the available models, confirming that the parameters governing the failure of reinforced concrete slabs subjected to blast are the tensile strength and softening behaviour after failure. Based on these results we have developed a constitutive model for concrete at high strain rates, which only takes into account the ultimate tensile strength. This model is based on the embedded Cohesive Crack Model with Strong Discontinuity Approach developed by Planas and Sancho, which has proved its ability in predicting the tensile fracture of plain concrete elements. The model has been modified for its implementation in the commercial explicit integration program LS-DYNA, using hexahedral finite elements and incorporating the dependence of the strain rate, to allow for its use in dynamic domain. The model is strictly local and does not require remeshing nor prior knowledge of the crack path. This constitutive model has been used to simulate two experimental campaigns, confirming the hypothesis that the failure of concrete elements subjected to explosions is governed by their tensile response, being of particular relevance the softening behavior of concrete.

An efficient nonlinear transformation for the numerical computation of the singular integrals appearing in the 2-D Boundary Element Method

We discuss several methods, based on coordinate transformations, for the evaluation of singular and quasisingular integrals in the direct Boundary Element Method. An intrinsec error of some of these methods is detected. Two new transformations are suggested which improve on those currently available.