915 resultados para General - statistics and numerical data
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An experimental and numerical study of ballistic impacts on steel plates at various temperatures (700ºC, 400ºC and room temperature) has been carried out. The motivation for this work is the blade‐off event that may occur inside a jet engine turbine. However, as a first attempt to understand this complex loading process, a somewhat simpler approach is carried out in the present work. The material used in this study is the FV535 martensitic stainless steel, which is one of the most commonly used materials for turbine casings. Based on material test data, a Modified Johnson‐Cook (MJC) model was calibrated for numerical simulations using the LS‐DYNA explicit finite element code (see Figure 1). To check the mesh size sensitivity, 2D axisymmetric finite element models with three different mesh sizes and configurations were used for the various temperatures. Two fixed meshes with 64 and 128 elements over the 2mm thick plate and one mesh with 32 elements over the thickness with adaptive remeshing were used in the simulations. The formation of adiabatic shear bands in the perforation process has been found critical in order to achieve good results. Adiabatic shear bands are formed by the temperature rise due to the accumulation of plastic strain during impact (see Figure 2). The influence of the thermal softening in the plastic model has hence been analyzed for the room temperature impact tests, where the temperature gradient is highest
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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.
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This paper present an environmental contingency forecasting tool based on Neural Networks (NN). Forecasting tool analyzes every hour and daily Sulphur Dioxide (SO2) concentrations and Meteorological data time series. Pollutant concentrations and meteorological variables are self-organized applying a Self-organizing Map (SOM) NN in different classes. Classes are used in training phase of a General Regression Neural Network (GRNN) classifier to provide an air quality forecast. In this case a time series set obtained from Environmental Monitoring Network (EMN) of the city of Salamanca, Guanajuato, México is used. Results verify the potential of this method versus other statistical classification methods and also variables correlation is solved.
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Crystallization and grain growth technique of thin film silicon are among the most promising methods for improving efficiency and lowering cost of solar cells. A major advantage of laser crystallization and annealing over conventional heating methods is its ability to limit rapid heating and cooling to thin surface layers. Laser energy is used to heat the amorphous silicon thin film, melting it and changing the microstructure to polycrystalline silicon (poly-Si) as it cools. Depending on the laser density, the vaporization temperature can be reached at the center of the irradiated area. In these cases ablation effects are expected and the annealing process becomes ineffective. The heating process in the a-Si thin film is governed by the general heat transfer equation. The two dimensional non-linear heat transfer equation with a moving heat source is solve numerically using the finite element method (FEM), particularly COMSOL Multiphysics. The numerical model help to establish the density and the process speed range needed to assure the melting and crystallization without damage or ablation of the silicon surface. The samples of a-Si obtained by physical vapour deposition were irradiated with a cw-green laser source (Millennia Prime from Newport-Spectra) that delivers up to 15 W of average power. The morphology of the irradiated area was characterized by confocal laser scanning microscopy (Leica DCM3D) and Scanning Electron Microscopy (SEM Hitachi 3000N). The structural properties were studied by micro-Raman spectroscopy (Renishaw, inVia Raman microscope).
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A numerical and experimental study of ballistic impacts at various temperatures on precipitation hardened Inconel 718 nickel-base superalloy plates has been performed. A coupled elastoplastic-damage constitutive model with Lode angle dependent failure criterion has been implemented in LS-DYNA non-linear finite element code to model the mechanical behaviour of such an alloy. The ballistic impact tests have been carried out at three temperatures: room temperature (25 °C), 400 °C and 700 °C. The numerical study showed that the mesh size is crucial to predict correctly the shear bands detected in the tested plates. Moreover, the mesh size convergence has been achieved for element sizes on the same order that the shear bands. The residual velocity as well as the ballistic limit prediction has been considered excellent for high temperature ballistic tests. Nevertheless, the model has been less accurate for the numerical simulations performed at room temperature, being though in reasonable agreement with the experimental data. Additionally, the influence that the Lode angle had on quasi-static failure patterns such as cup-cone and slanted failure has been studied numerically. The study has revealed that the combined action of weakened constitutive equations and Lode angle dependent failure criterion has been necessary to predict the previously-mentioned failure patterns
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The stabilizing effect of grouping rotor blades in pairs has been assessed both, numerically and experimentally. The bending and torsion modes of a low aspect ratio high speed turbine cascade tested in the non-rotating test facility at EPFL (Ecole Polytechnique Fédérale de Lausanne) have been chosen as the case study. The controlled vibration of 20 blades in travelling wave form was performed by means of an electromagnetic excitation system, enabling the adjustement of the vibration amplitude and inter blade phase at a given frequency. Unsteady pressure transducers located along the blade mid-section were used to obtain the modulus and phase of the unsteady pressure caused by the airfoil motion. The stabilizing effect of the torsion mode was clearly observed both in the experiments and the simulations, however the effect of grouping the blades in pairs in the minimum damping at the tested frequency was marginal in the bending mode. A numerical tool was validated using the available experimental data and then used to extend the results at lower and more relevant reduced frequencies. It is shown that the stabilizing effect exists for the bending and torsion modes in the frequency range typical of low-pressure turbines. It is concluded that the stabilizing effect of this configuration is due to the shielding effect of the pressure side of the airfoil that defines the passage of the pair on the suction side of the same passage, since the relative motion between both is null. This effect is observed both in the experiments and simulations.
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Los tipos de datos concurrentes son implementaciones concurrentes de las abstracciones de datos clásicas, con la diferencia de que han sido específicamente diseñados para aprovechar el gran paralelismo disponible en las modernas arquitecturas multiprocesador y multinúcleo. La correcta manipulación de los tipos de datos concurrentes resulta esencial para demostrar la completa corrección de los sistemas de software que los utilizan. Una de las mayores dificultades a la hora de diseñar y verificar tipos de datos concurrentes surge de la necesidad de tener que razonar acerca de un número arbitrario de procesos que invocan estos tipos de datos de manera concurrente. Esto requiere considerar sistemas parametrizados. En este trabajo estudiamos la verificación formal de propiedades temporales de sistemas concurrentes parametrizados, poniendo especial énfasis en programas que manipulan estructuras de datos concurrentes. La principal dificultad a la hora de razonar acerca de sistemas concurrentes parametrizados proviene de la interacción entre el gran nivel de concurrencia que éstos poseen y la necesidad de razonar al mismo tiempo acerca de la memoria dinámica. La verificación de sistemas parametrizados resulta en sí un problema desafiante debido a que requiere razonar acerca de estructuras de datos complejas que son accedidas y modificadas por un numero ilimitado de procesos que manipulan de manera simultánea el contenido de la memoria dinámica empleando métodos de sincronización poco estructurados. En este trabajo, presentamos un marco formal basado en métodos deductivos capaz de ocuparse de la verificación de propiedades de safety y liveness de sistemas concurrentes parametrizados que manejan estructuras de datos complejas. Nuestro marco formal incluye reglas de prueba y técnicas especialmente adaptadas para sistemas parametrizados, las cuales trabajan en colaboración con procedimientos de decisión especialmente diseñados para analizar complejas estructuras de datos concurrentes. Un aspecto novedoso de nuestro marco formal es que efectúa una clara diferenciación entre el análisis del flujo de control del programa y el análisis de los datos que se manejan. El flujo de control del programa se analiza utilizando reglas de prueba y técnicas de verificación deductivas especialmente diseñadas para lidiar con sistemas parametrizados. Comenzando a partir de un programa concurrente y la especificación de una propiedad temporal, nuestras técnicas deductivas son capaces de generar un conjunto finito de condiciones de verificación cuya validez implican la satisfacción de dicha especificación temporal por parte de cualquier sistema, sin importar el número de procesos que formen parte del sistema. Las condiciones de verificación generadas se corresponden con los datos manipulados. Estudiamos el diseño de procedimientos de decisión especializados capaces de lidiar con estas condiciones de verificación de manera completamente automática. Investigamos teorías decidibles capaces de describir propiedades de tipos de datos complejos que manipulan punteros, tales como implementaciones imperativas de pilas, colas, listas y skiplists. Para cada una de estas teorías presentamos un procedimiento de decisión y una implementación práctica construida sobre SMT solvers. Estos procedimientos de decisión son finalmente utilizados para verificar de manera automática las condiciones de verificación generadas por nuestras técnicas de verificación parametrizada. Para concluir, demostramos como utilizando nuestro marco formal es posible probar no solo propiedades de safety sino además de liveness en algunas versiones de protocolos de exclusión mutua y programas que manipulan estructuras de datos concurrentes. El enfoque que presentamos en este trabajo resulta ser muy general y puede ser aplicado para verificar un amplio rango de tipos de datos concurrentes similares. Abstract Concurrent data types are concurrent implementations of classical data abstractions, specifically designed to exploit the great deal of parallelism available in modern multiprocessor and multi-core architectures. The correct manipulation of concurrent data types is essential for the overall correctness of the software system built using them. A major difficulty in designing and verifying concurrent data types arises by the need to reason about any number of threads invoking the data type simultaneously, which requires considering parametrized systems. In this work we study the formal verification of temporal properties of parametrized concurrent systems, with a special focus on programs that manipulate concurrent data structures. The main difficulty to reason about concurrent parametrized systems comes from the combination of their inherently high concurrency and the manipulation of dynamic memory. This parametrized verification problem is very challenging, because it requires to reason about complex concurrent data structures being accessed and modified by threads which simultaneously manipulate the heap using unstructured synchronization methods. In this work, we present a formal framework based on deductive methods which is capable of dealing with the verification of safety and liveness properties of concurrent parametrized systems that manipulate complex data structures. Our framework includes special proof rules and techniques adapted for parametrized systems which work in collaboration with specialized decision procedures for complex data structures. A novel aspect of our framework is that it cleanly differentiates the analysis of the program control flow from the analysis of the data being manipulated. The program control flow is analyzed using deductive proof rules and verification techniques specifically designed for coping with parametrized systems. Starting from a concurrent program and a temporal specification, our techniques generate a finite collection of verification conditions whose validity entails the satisfaction of the temporal specification by any client system, in spite of the number of threads. The verification conditions correspond to the data manipulation. We study the design of specialized decision procedures to deal with these verification conditions fully automatically. We investigate decidable theories capable of describing rich properties of complex pointer based data types such as stacks, queues, lists and skiplists. For each of these theories we present a decision procedure, and its practical implementation on top of existing SMT solvers. These decision procedures are ultimately used for automatically verifying the verification conditions generated by our specialized parametrized verification techniques. Finally, we show how using our framework it is possible to prove not only safety but also liveness properties of concurrent versions of some mutual exclusion protocols and programs that manipulate concurrent data structures. The approach we present in this work is very general, and can be applied to verify a wide range of similar concurrent data types.
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This paper presents an overview of depth averaged modelling of fast catastrophic landslides where coupling of solid skeleton and pore fluid (air and water) is important. The first goal is to show how Biot-Zienkiewicz models can be applied to develop depth integrated, coupled models. The second objective of the paper is to consider a link which can be established between rheological and constitutive models. Perzyna´s viscoplasticity can be considered a general framework within which rheological models such as Bingham and cohesive frictional fluids can be derived. Among the several alternative numerical models, we will focus here on SPH which has not been widely applied by engineers to model landslide propagation. We propose an improvement, based on combining Finite Difference meshes associated to SPH nodes to describe pore pressure evolution inside the landslide mass. We devote a Section to analyze the performance of the models, considering three sets of tests and examples which allows to assess the model performance and limitations: (i) Problems having an analytical solution, (ii) Small scale laboratory tests, and (iii) Real cases for which we have had access to reliable information
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This paper gives three related results: (i) a new, simple, fast, monotonically converging algorithm for deriving the L1-median of a data cloud in ℝd, a problem that can be traced to Fermat and has fascinated applied mathematicians for over three centuries; (ii) a new general definition for depth functions, as functions of multivariate medians, so that different definitions of medians will, correspondingly, give rise to different dept functions; and (iii) a simple closed-form formula of the L1-depth function for a given data cloud in ℝd.
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This report sheds light on the fundamental questions and underlying tensions between current policy objectives, compliance strategies and global trends in online personal data processing, assessing the existing and future framework in terms of effective regulation and public policy. Based on the discussions among the members of the CEPS Digital Forum and independent research carried out by the rapporteurs, policy conclusions are derived with the aim of making EU data protection policy more fit for purpose in today’s online technological context. This report constructively engages with the EU data protection framework, but does not provide a textual analysis of the EU data protection reform proposal as such.
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Among many other problems, the migration, humanitarian and policy crises in the European Union in 2015 and early 2016 have highlighted a pressing need for reliable, timely and comparable statistical data on migration, asylum and arrivals at national borders. In this fast-moving policy field, data production and the timeliness of dissemination have seen some improvements but the sources of data remain largely unchanged at national level. In this paper the author examines the reasons for some of the problems with the data for policy and for public discussion, and makes a set of recommendations that call for a complete and updated inventory of data sources and for an evaluation of the quality of data used for policy-making.
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Il presente elaborato è incentrato sulla modellizzazione del plasma di bordo nei dispositivi per la produzione di energia da fusione nucleare noti come tokamak. La tecnologia che nel corso di tutta la seconda metà del XX secolo fino ad oggi è stata sviluppata a questo fine deve necessariamente scontrarsi con alcuni limiti. Nei tokamak il confinamento del plasma è di tipo magnetico e vincola le particelle a muoversi di moto elicoidale all'interno del vessel, tuttavia il confinamento non risulta perfetto e parte dell'energia si scarica sulle pareti della camera, rischiando pertanto di fondere i materiali. Alcune strategie possono essere messe in atto per limitare questo problema, per esempio agendo sulla geometria del tokamak, oppure sulla fisica, inducendo nel plasma una data concentrazione di impurezze che ionizzino irraggiando parte dell'energia di plasma. Proprio tale meccanismo di perdita è stato simulato in un modello monodimensionale di plasma monofluido di bordo. I risultati del codice numerico relativo al modello dimostrano che per concentrazioni di impurezze crescenti è possibile diminuire in modo significativo flusso di calore e temperatura al divertore. Per di più risulta possibile controllare la posizione del fronte di irraggiamento per mezzo di parametri di controllo del plasma quali la pressione. Si osserva inoltre l'insorgere del cosiddetto fenomeno di biforcazione alle basse temperature di divertore, fenomeno in cui il plasma si comporta in modo instabile a causa di fenomeni fisici tipici delle basse energie ("detachment") e a seguito del quale può improvvisamente spegnersi (disruzione). Infine lo stesso modello è stato migliorato inserendo l'ipotesi di plasma bifluido. Anche per gli ioni viene osservato il fenomeno di biforcazione. I risultati numerici evidenziano le dinamiche dello scambio energetico fra le specie gettando le basi di una progettazione efficiente della chimica del plasma finalizzata al raffreddamento del divertore.
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The present understanding of the initiation of boudinage and folding structures is based on viscosity contrasts and stress exponents, considering an intrinsically unstable state of the layer. The criterion of localization is believed to be prescribed by geometry-material interactions, which are often encountered in natural structures. An alternative localization phenomenon has been established for ductile materials, in which instability emerges for critical material parameters and loading rates from homogeneous conditions. In this thesis, conditions are sought under which this type of instability prevails and whether localization in geological materials necessarily requires a trigger by geometric imperfections. The relevance of critical deformation conditions, material parameters and the spatial configuration of instabilities are discussed in a geological context. In order to analyze boudinage geometries, a numerical eigenmode analysis is introduced. This method allows determining natural frequencies and wavelengths of a structure and inducing perturbations on these frequencies. In the subsequent coupled thermo-mechanical simulations, using a grain size evolution and end-member flow laws, localization emerges when material softening through grain size sensitive viscous creep sets in. Pinch-and-swell structures evolve along slip lines through a positive feedback between the matrix response and material bifurcations inside the layer, independent from the mesh-discretization length scale. Since boudinage and folding are considered to express the same general instability, both structures should arise independently of the sign of the loading conditions and for identical material parameters. To this end, the link between material to energy instabilities is approached by means of bifurcation analyses of the field equations and finite element simulations of the coupled system of equations. Boudinage and folding structures develop at the same critical energy threshold, where dissipative work by temperature-sensitive creep overcomes the diffusive capacity of the layer. This finding provides basis for a unified theory for strain localization in layered ductile materials. The numerical simulations are compared to natural pinch-and-swell microstructures, tracing the adaption of grain sizes, textures and creep mechanisms in calcite veins. The switch from dislocation to diffusion creep relates to strain-rate weakening, which is induced by dissipated heat from grain size reduction, and marks the onset of continuous necking. The time-dependent sequence uncovers multiple steady states at different time intervals. Microstructurally and mechanically stable conditions are finally expressed in the pinch-and-swell end members. The major outcome of this study is that boudinage and folding can be described as the same coupled energy-mechanical bifurcation, or as one critical energy attractor. This finding allows the derivation of critical deformation conditions and fundamental material parameters directly from localized structures in the field.
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A vast amount of data shows that angiogenesis has a pivotal role in tumor growth, progression, invasiveness and metastasis. This is a complex process involving essential signaling pathways such as vascular endothelial growth factor (VEGF) and Notch in vasculature, as well as additional players such as bone marrow-derived endothelial progenitor cells. Primary tumor cells, stromal cells and cancer stem cells strongly influence vessel growth in tumors. Better understanding of the role of the different pathways and the crosstalk between different cells during tumor angiogenesis are crucial factors for developing more effective anticancer therapies. Targeting angiogenic factors from the VEGF family has become an effective strategy to inhibit tumor growth and so far the most successful results are seen in metastatic colorectal cancer (CRC), renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLL). Despite the initial enthusiasm, the angiogenesis inhibitors showed only moderate survival benefit as monotherapy, along with a high cost and many side effects. Obviously, other important pathways may affect the angiogenic switch, among them Notch signaling pathway attracted a large interest because its ubiquitous role in carcinogenesis and angiogenesis. Herein we present the basics for VEGF and Notch signaling pathways and current advances of targeting them in antiangiogenic, antitumor therapy.
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Item 142-C