Microstructural and mechanical characterization of tungsten based materials for fusion reactors

El wolframio (W) y sus aleaciones se consideran los mejores candidatos para la construcción del divertor en la nueva generación de reactores de fusión nuclear. Este componente va a recibir las cargas térmicas más elevadas durante el funcionamiento del reactor ya que estará en contacto directo con el plasma. En los últimos años, después de un profundo análisis y siguiendo una estrategia de reducción de costes, la Organización de ITER tomó la decisión de construir el divertor integramente de wolframio desde el principio. Por ello, el wolframio no sólo actuará como material en contacto con el plasma (PFM), sino que también tendría aplicaciones estructurales. El wolframio, debido a sus excelentes propiedades termo-físicas, cumple todos los requerimientos para ser utilizado como PFM, sin embargo, su inherente fragilidad pone en peligro su uso estructural. Por tanto, uno de los principales objetivos de esta tesis es encontrar una aleación de wolframio con menor fragilidad. Durante éste trabajo, se realizó la caracterización microstructural y mecánica de diferentes materiales basados en wolframio. Sin embargo, ésta tarea es un reto debido a la pequeña cantidad de material suministrado, su reducido tamaño de grano y fragilidad. Por ello, para una correcta medida de todas las propiedades físicas y mecánicas se utilizaron diversas técnicas experimentales. Algunas de ellas se emplean habitualmente como la nanoindentación o los ensayos de flexión en tres puntos (TPB). Sin embargo, otras fueron especificamente desarrolladas e implementadas durante el desarrollo de esta tesis como es el caso de la medida real de la tenacidad de fractura en los materiales masivos, o de las medidas in situ de la tenacidad de fractura en las láminas delgadas de wolframio. Diversas composiciones de aleaciones de wolframio masivas (W-1% Y2O3, W-2% V-0.5% Y2O3, W-4% V-0.5% Y2O3, W-2% Ti-1% La2O3 y W-4% Ti-1% La2O3) se han estudiado y comparado con un wolframio puro producido en las mismas condiciones. Estas aleaciones, producidas por ruta pulvimetalúrgica de aleado mecánico (MA) y compactación isostática en caliente (HIP), fueron microstructural y mecánicamente caracterizadas desde 77 hasta 1473 K en aire y en alto vacío. Entre otras propiedades físicas y mecánicas se midieron la dureza, el módulo elástico, la resistencia a flexión y la tenacidad de fractura para todas las aleaciones. Finalmente se analizaron las superficies de fractura después de los ensayos de TPB para relacionar los micromecanismos de fallo con el comportamiento macroscópico a rotura. Los resultados obtenidos mostraron un comportamiento mecánico frágil en casi todo el intervalo de temperaturas y para casi todas las aleaciones sin mejoría de la temperatura de transición dúctil-frágil (DBTT). Con el fin de encontrar un material base wolframio con una DBTT más baja se realizó también un estudio, aún preliminar, de láminas delgadas de wolframio puro y wolframio dopado con 0.005wt.% potasio (K). Éstas láminas fueron fabricadas industrialmente mediante sinterizado y laminación en caliente y en frío y se sometieron posteriormente a un tratamiento térmico de recocido desde 1073 hasta 2673 K. Se ha analizado la evolución de su microestructura y las propiedades mecánicas al aumentar la temperatura de recocido. Los resultados mostraron la estabilización de los granos de wolframio con el incremento de la temperatura de recocido en las láminas delgadas de wolframio dopado con potasio. Sin embargo, es necesario realizar estudios adicionales para entender mejor la microstructura y algunas propiedades mecánicas de estos materiales, como la tenacidad de fractura. Tungsten (W) and tungsten-based alloys are considered to be the best candidate materials for fabricating the divertor in the next-generation nuclear fusion reactors. This component will experience the highest thermal loads during the operation of a reactor since it directly faces the plasma. In recent years, after thorough analysis that followed a strategy of cost reduction, the ITER Organization decided to built a full-tunsgten divertor before the first nuclear campaigns. Therefore, tungsten will be used not only as a plasma-facing material (PFM) but also in structural applications. Tungsten, due to its the excellent thermo-physical properties fulfils the requirements of a PFM, however, its use in structural applications is compromised due to its inherent brittleness. One of the objectives of this phD thesis is therefore, to find a material with improved brittleness behaviour. The microstructural and mechanical characterisation of different tunsgten-based materials was performed. However, this is a challenging task because of the reduced laboratory-scale size of the specimens provided, their _ne microstructure and their brittleness. Consequently, many techniques are required to ensure an accurate measurement of all the mechanical and physical properties. Some of the applied methods have been widely used such as nanoindentation or three-point bending (TPB) tests. However, other methods were specifically developed and implemented during this work such as the measurement of the real fracture toughness of bulk-tunsgten alloys or the in situ fracture toughness measurements of very thin tungsten foils. Bulk-tunsgten materials with different compositions (W-1% Y2O3, W-2% V- 0.5% Y2O3, W-4% V-0.5% Y2O3, W-2% Ti-1% La2O3 and W-4% Ti-1% La2O3) were studied and compared with pure tungsten processed under the same conditions. These alloys, produced by a powder metallurgical route of mechanical alloying (MA) and hot isostatic pressing (HIP), were microstructural and mechanically characterised from 77 to 1473 K in air and under high vacuum conditions. Hardness, elastic modulus, flexural strength and fracture toughness for all of the alloys were measured in addition to other physical and mechanical properties. Finally, the fracture surfaces after the TPB tests were analysed to correlate the micromechanisms of failure with the macroscopic behaviour. The results reveal brittle mechanical behaviour in almost the entire temperature range for the alloys and micromechanisms of failure with no improvement in the ductile-brittle transition temperature (DBTT). To continue the search of a tungsten material with lowered DBTT, a preliminary study of pure tunsgten and 0.005 wt.% potassium (K)-doped tungsten foils was also performed. These foils were industrially produced by sintering and hot and cold rolling. After that, they were annealed from 1073 to 2673 K to analyse the evolution of the microstructural and mechanical properties with increasing annealing temperature. The results revealed the stabilisation of the tungsten grains with increasing annealing temperature in the potassium-doped tungsten foil. However, additional studies need to be performed to gain a better understanding of the microstructure and mechanical properties of these materials such as fracture toughness.

Application of PZT and FBG impedance sensors for structural health monitoring of reinforced concrete beams strengthened with FRP composite materials

Esta Tesis tiene como objetivo principal el desarrollo de métodos de identificación del daño que sean robustos y fiables, enfocados a sistemas estructurales experimentales, fundamentalmente a las estructuras de hormigón armado reforzadas externamente con bandas fibras de polímeros reforzados (FRP). El modo de fallo de este tipo de sistema estructural es crítico, pues generalmente es debido a un despegue repentino y frágil de la banda del refuerzo FRP originado en grietas intermedias causadas por la flexión. La detección de este despegue en su fase inicial es fundamental para prevenir fallos futuros, que pueden ser catastróficos. Inicialmente, se lleva a cabo una revisión del método de la Impedancia Electro-Mecánica (EMI), de cara a exponer sus capacidades para la detección de daño. Una vez la tecnología apropiada es seleccionada, lo que incluye un analizador de impedancias así como novedosos sensores PZT para monitorización inteligente, se ha diseñado un procedimiento automático basado en los registros de impedancias de distintas estructuras de laboratorio. Basándonos en el hecho de que las mediciones de impedancias son posibles gracias a una colocación adecuada de una red de sensores PZT, la estimación de la presencia de daño se realiza analizando los resultados de distintos indicadores de daño obtenidos de la literatura. Para que este proceso sea automático y que no sean necesarios conocimientos previos sobre el método EMI para realizar un experimento, se ha diseñado e implementado un Interfaz Gráfico de Usuario, transformando la medición de impedancias en un proceso fácil e intuitivo. Se evalúa entonces el daño a través de los correspondientes índices de daño, intentando estimar no sólo su severidad, sino también su localización aproximada. El desarrollo de estos experimentos en cualquier estructura genera grandes cantidades de datos que han de ser procesados, y algunas veces los índices de daño no son suficientes para una evaluación completa de la integridad de una estructura. En la mayoría de los casos se pueden encontrar patrones de daño en los datos, pero no se tiene información a priori del estado de la estructura. En este punto, se ha hecho una importante investigación en técnicas de reconocimiento de patrones particularmente en aprendizaje no supervisado, encontrando aplicaciones interesantes en el campo de la medicina. De ahí surge una idea creativa e innovadora: detectar y seguir la evolución del daño en distintas estructuras como si se tratase de un cáncer propagándose por el cuerpo humano. En ese sentido, las lecturas de impedancias se emplean como información intrínseca de la salud de la propia estructura, de forma que se pueden aplicar las mismas técnicas que las empleadas en la investigación del cáncer. En este caso, se ha aplicado un algoritmo de clasificación jerárquica dado que ilustra además la clasificación de los datos de forma gráfica, incluyendo información cualitativa y cuantitativa sobre el daño. Se ha investigado la efectividad de este procedimiento a través de tres estructuras de laboratorio, como son una viga de aluminio, una unión atornillada de aluminio y un bloque de hormigón reforzado con FRP. La primera ayuda a mostrar la efectividad del método en sencillos escenarios de daño simple y múltiple, de forma que las conclusiones extraídas se aplican sobre los otros dos, diseñados para simular condiciones de despegue en distintas estructuras. Demostrada la efectividad del método de clasificación jerárquica de lecturas de impedancias, se aplica el procedimiento sobre las estructuras de hormigón armado reforzadas con bandas de FRP objeto de esta tesis, detectando y clasificando cada estado de daño. Finalmente, y como alternativa al anterior procedimiento, se propone un método para la monitorización continua de la interfase FRP-Hormigón, a través de una red de sensores FBG permanentemente instalados en dicha interfase. De esta forma, se obtienen medidas de deformación de la interfase en condiciones de carga continua, para ser implementadas en un modelo de optimización multiobjetivo, cuya solución se haya por medio de una expansión multiobjetivo del método Particle Swarm Optimization (PSO). La fiabilidad de este último método de detección se investiga a través de sendos ejemplos tanto numéricos como experimentales. ABSTRACT This thesis aims to develop robust and reliable damage identification methods focused on experimental structural systems, in particular Reinforced Concrete (RC) structures externally strengthened with Fiber Reinforced Polymers (FRP) strips. The failure mode of this type of structural system is critical, since it is usually due to sudden and brittle debonding of the FRP reinforcement originating from intermediate flexural cracks. Detection of the debonding in its initial stage is essential thus to prevent future failure, which might be catastrophic. Initially, a revision of the Electro-Mechanical Impedance (EMI) method is carried out, in order to expose its capabilities for local damage detection. Once the appropriate technology is selected, which includes impedance analyzer as well as novel PZT sensors for smart monitoring, an automated procedure has been design based on the impedance signatures of several lab-scale structures. On the basis that capturing impedance measurements is possible thanks to an adequately deployed PZT sensor network, the estimation of damage presence is done by analyzing the results of different damage indices obtained from the literature. In order to make this process automatic so that it is not necessary a priori knowledge of the EMI method to carry out an experimental test, a Graphical User Interface has been designed, turning the impedance measurements into an easy and intuitive procedure. Damage is then assessed through the analysis of the corresponding damage indices, trying to estimate not only the damage severity, but also its approximate location. The development of these tests on any kind of structure generates large amounts of data to be processed, and sometimes the information provided by damage indices is not enough to achieve a complete analysis of the structural health condition. In most of the cases, some damage patterns can be found in the data, but none a priori knowledge of the health condition is given for any structure. At this point, an important research on pattern recognition techniques has been carried out, particularly on unsupervised learning techniques, finding interesting applications in the medicine field. From this investigation, a creative and innovative idea arose: to detect and track the evolution of damage in different structures, as if it were a cancer propagating through a human body. In that sense, the impedance signatures are used to give intrinsic information of the health condition of the structure, so that the same clustering algorithms applied in the cancer research can be applied to the problem addressed in this dissertation. Hierarchical clustering is then applied since it also provides a graphical display of the clustered data, including quantitative and qualitative information about damage. The performance of this approach is firstly investigated using three lab-scale structures, such as a simple aluminium beam, a bolt-jointed aluminium beam and an FRP-strengthened concrete specimen. The first one shows the performance of the method on simple single and multiple damage scenarios, so that the first conclusions can be extracted and applied to the other two experimental tests, which are designed to simulate a debonding condition on different structures. Once the performance of the impedance-based hierarchical clustering method is proven to be successful, it is then applied to the structural system studied in this dissertation, the RC structures externally strengthened with FRP strips, where the debonding failure in the interface between the FRP and the concrete is successfully detected and classified, proving thus the feasibility of this method. Finally, as an alternative to the previous approach, a continuous monitoring procedure of the FRP-Concrete interface is proposed, based on an FBGsensors Network permanently deployed within that interface. In this way, strain measurements can be obtained under controlled loading conditions, and then they are used in order to implement a multi-objective model updating method solved by a multi-objective expansion of the Particle Swarm Optimization (PSO) method. The feasibility of this last proposal is investigated and successfully proven on both numerical and experimental RC beams strengthened with FRP.

Papel de la interleuquina 23 en la diferenciación hacia Th17

The incidence of inflammatory and autoimmune diseases has increased among developed countries in the past 30 years, creating a demand for the development of effective and economic therapies for these diseases. Interleukin 23 (IL-23) is a pro-inflammatory cytokine whose increased production has been shown to play a key role in the establishment and maintenance of inflammatory and autoimmune diseases in different murine models such as inflammatory bowel disease, psoriasis and experimental autoimmune encephalomyelitis. More importantly, increased levels of IL-23 have been found in biopsies from patients with Crohn’s disease and ulcerative colitis, and psoriasis. The pathological consequences of excessive IL-23 signalling have been linked to its ability to promote the production of interleukin 17 (IL-17), particularly in the subpopulation of CD4 T cells Th17. However, the precise molecular mechanisms by which IL-23 sustains the Th17 response and induces pathogenic effector functions in these cells remain largely unknown. The global objective of the experiments carried out in this work was to determine the effect of IL-23 on the proliferation, survival and IL-17 and interferon gamma (IFN-ɣ) production in Th17 cells. These experiments have shown that IL-23 does not promote proliferation or survival of in vitro generated Th17 cells, and that there is no difference in the production of IL -17 in the absence or presence of IL -23. The IL-23 receptor, like other cytokine receptors, lacks intrinsic enzymatic activity. Instead, IL-23 receptor associates with members of the Janus tyrosine kinase family (Jaks). Cytokine binding to a Jak-associated receptor triggers the activation of the Signal Transducers and Activators of Transcription (STAT) family of transcription factors. Previous work indicated that the IL-23 receptor complex is associated with the tyrosine kinases Jak2 and Tyk2 that promote STAT3 phosphorylation. Subsequent studies showed that IL23 activation of STAT3 induces the expression of the transcription factor RORγt, which is crucial for IL-17 production. This work has explored the IL-23 signalling cascade, determining the optimal conditions for STAT3 activation and demonstrating the activation of other transcription factors such as STAT4, STAT5 and STAT1 that contribute to IL-23-mediated signalling pathways.

Estudio teórico-experimental para la mejora de la resistencia estructural de autocares basado en el diseño de uniones y asientos

La presente tesis analiza la mejora de la resistencia estructural ante vuelco de autocares enfocando dos vías de actuación: análisis y propuestas de requisitos reglamentarios a nivel europeo y la generación de herramientas que ayuden al diseño y a la verificación de estos requisitos. Los requisitos reglamentarios de resistencia estructural a vuelco contemplan la superestructura de los vehículos pero no para los asientos y sistemas de retención. La influencia de los pasajeros retenidos es superior a la incluida en reglamentación (Reg. 66.01) debiendo considerarse unida al vehículo un porcentaje de la masa de los pasajeros del 91% para cinturón de tres puntos y del 52% para cinturón subabdominal frente al 50% reglamentario para todos los casos. Se ha determinado la cinemática y dinámica del vuelco normativo en sus diferentes fases, formulando las energías en las fases iniciales (hasta el impacto contra el suelo) y determinando la fase final de deformación a través del análisis secuencial de ensayos de módulos reales. Se han determinado los esfuerzos para los asientos que se dividen en dos fases diferenciadas temporalmente: una primera debida a la deformación estructural y una segunda debida al esfuerzo del pasajero retenido que se produce en sentido opuesto (con una deceleración del pasajero en torno a 3.3 g). Se ha caracterizado a través de ensayos cuasi.estáticos el comportamiento de perfiles a flexión y de las uniones estructurales de las principales zonas del vehículo (piso, ventana y techo) verificándose la validez del comportamiento plástico teórico Kecman.García para perfiles de hasta 4 mm de espesor y caracterizando la resistencia y rigidez en la zona elástica de las uniones en función del tipo de refuerzo, materiales y perfiles (análisis de más de 180 probetas). Se ha definido un método de ensayo cuasi.estático para asientos ante esfuerzos de vuelco, ensayándose 19 butacas y determinándose que son resistentes (salvo las uniones a vehículo con pinzas), que son capaces de absorber hasta más de un 17% de la energía absorbida, aunque algunos necesitan optimización para llegar a contribuir en el mecanismo de deformación estructural. Se han generado modelos simplificados para introducir en los modelos barra.rótula plástica: un modelo combinado unión+rótula plástica (que incluye la zona de rigidez determinada en función del tipo de unión) para la superestructura y un modelo simplificado de muelles no.lineales para los asientos. Igualmente se ha generado la metodología de diseño a través de ensayos virtuales con modelos de detalle de elementos finitos tanto de las uniones como de los asientos. Se ha propuesto una metodología de diseño basada en obtener el “mecanismo óptimo de deformación estructural” (elevando la zona de deformación lateral a nivel de ventana y en pilar o en costilla en techo). Para ello se abren dos vías: diseño de la superestructura (selección de perfiles y generación de uniones resistentes) o combinación con asientos (que en lugar de solo resistir las cargas pueden llegar a modificar el mecanismo de deformación). Se ha propuesto una metodología de verificación alternativa al vuelco de vehículo completo que contempla el cálculo cuasi.estático con modelos simplificados barra.rótula plástica más el ensayo de una sección representativa con asientos y utillajes antropomórficos retenidos que permite validar el diseño de las uniones, determinar el porcentaje de energía que debe absorberse por deformación estructural (factor C) y verificar el propio asiento como sistema de retención. ABSTRACT This research analyzes the improvement of the structural strength of buses and coaches under rollover from two perspectives: regulatory requirements at European level and generation of tools that will help to the design and to the verification of requirements. European Regulations about rollover structural strength includes requirements for the superstructure of the vehicles but not about seats, anchorages and restraint systems. The influence of the retained passengers is higher than the one included currently in the Regulations (Reg. 66.01), being needed to consider a 91% of the passenger mass as rigidly joint to the vehicle (for 3 points’ belt, a 52% for 2 points’ belt) instead of the 50% included in the Regulation. Kinematic and dynamic of the normative rollover has been determined from testing of different sections, formulating the energies of the first phases (up to the first impact with the ground) and determining the last deformation phase through sequential analysis of movements and deformations. The efforts due to rollover over the seats have been established, being divided in two different temporal phases: a first one due to the structural deformation of the vehicle and a second one due to the effort of the restrained passenger being this second one in opposite sense (with a passenger deceleration around 3.3 g). From quasi.static testing, the behavior of the structural tubes under flexural loads, including the principal joints in the vehicle (floor, window and roof), the validity of the theoretical plastic behavior according Kecman.García theories have been verified up to 4 mm of thickness. Strength of the joints as well as the stiffness of the elastic zone has been determined in function of main parameters: type of reinforcement, materials and section of the tubes (more than 180 test specimens). It has been defined a quasi.static testing methodology to characterize the seats and restrain system behavior under rollover, testing 19 double seats and concluding that they are resistant (excepting clamping joints), that they can absorb more than a 17 of the absorbed energy, and that some of them need optimization to contribute in the structural deformation mechanism. It has been generated simplified MEF models, to analyze in a beam.plastic hinge model: a combined model joint+plastic hinge (including the stiffness depending on the type of joint) for the superstructure and a simplified model with non.lineal springs to represent the seats. It has been detailed methodologies for detailed design of joints and seats from virtual testing (MEF models). A design methodology based in the “optimized structural deformation mechanism” (increasing the height of deformation of the lateral up to window level) is proposed. Two possibilities are analyzed: design of the superstructure based on the selection of profiles and design of strength joints (were seats only resist the efforts and contribute in the energy absorption) or combination structure.seats, were seats contributes in the deformation mechanism. An alternative methodology to the rollover of a vehicle that includes the quasi.static calculation with simplified models “beam.joint+plastic hinge” plus the testing of a representative section of the vehicle including seats and anthropomorphic ballast restrained by the safety belts is presented. The test of the section allows validate the design of the joints, determine the percentage of energy to be absorbed by structural deformation (factor C) and verify the seat as a retention system.

Desarrollo de conglomerantes basados en hipótesis constructivas de pirámides egipcias del Reino Antiguo

En la presente tesis doctoral se revisan las principales hipótesis que intentan aclarar los procesos constructivos llevados a cabo para edificar las pirámides egipcias de las Dinastías III y IV, organizándose dichas teorías desde el punto de vista de los posibles materiales constituyentes. La investigación se ha centrado en la hipótesis heterodoxa que propone, como medio para ejecutar estas construcciones, la manufactura completa de la pirámide con piedra caliza conglomerada. Con este fin, se profundiza en artículos que tienen por objeto el análisis de muestras de material de estos monumentos, de piedras calizas naturales y de piedras calizas geopoliméricas, con objeto de determinar si la hipótesis constructiva mencionada es viable. Tomando como referencia la hipótesis constructiva estudiada, se adicionan morteros de cal aérea con carbonato de sodio (natrón) y metacaolín, analizando posteriormente las nuevas características de estos conglomerantes. El cementante descrito en la teoría constructiva se enmarca dentro de la química y tecnología de los polímeros sintéticos inorgánicos activados alcalinamente, también denominados geopolímeros. Se desarrolla una primera mezcla basada en los datos extraídos de la investigación precedente. Posteriormente, se realizan varios grupos de mezclas, en las que se parte de unas proporciones iniciales correspondientes al geopolímero teórico de la hipótesis constructiva. Sobre dichas proporciones se realizan incrementos en la cantidad de cal, y los productos obtenidos son ensayados, tomando datos de: dureza Shore C, velocidad de ultrasonidos, densidades, resistencia a compresión y a flexión, difracción de rayos X, análisis térmicos y microscopía electrónica de barrido. Los resultados derivados de introducir las adiciones, en las proporciones estudiadas, mejoran notablemente algunas características de los morteros de cal convencionales. ABSTRACT In the present PhD thesis the main hypotheses about the construction processes to build the Egyptian pyramids of Dynasties III and IV are reviewed. These theories are addressed from the point of view of their possible constituent materials. The research focuses on the heterodox hypothesis that proposes, as a means to perform these constructions, the complete manufacturing of the pyramid with limestone conglomerate. In this regard, a state of the art is set on the analysis of samples of material of these monuments, natural limestone and limestone geopolymeric, to determine if the constructive hypothesis is viable. Using this constructive hypothesis as a reference, aerial lime mortars are added with sodium carbonate (natron) and metakaolin, and the new characteristics of these resulting binders are then analyzed. The cementing described in the constructive theory belongs to the chemistry and the technology of synthetic inorganic alkali-activated polymers, also called geopolymer. Based on data obtained from previous research, a first mix is prepared. Subsequently, several groups of mixes are made, starting from theoretical initial ratios corresponding to the geopolymer that was presumably used in the constructive hypothesis. Increments in the amount of lime are made upon such proportion, and the resulting products are tested for data collection about: Shore C hardness, ultrasound velocity, densities, compressive and flexural strength, X-ray diffraction, thermal analysis and scanning electron microscopy. The results allow to conclude that, if in the studied proportions, additions improve significantly some of the characteristics of conventional lime mortars.

Estimación de la resistencia de estructuras de hormigón armado reforzadas a cortante mediante FRP

El empleo de refuerzos de FRP en vigas de hormigón armado es cada vez más frecuente por sus numerosas ventajas frente a otros métodos más tradicionales. Durante los últimos años, la técnica FRP-NSM, consistente en introducir barras de FRP sobre el recubrimiento de una viga de hormigón, se ha posicionado como uno de los mejores métodos de refuerzo y rehabilitación de estructuras de hormigón armado, tanto por su facilidad de montaje y mantenimiento, como por su rendimiento para aumentar la capacidad resistente de dichas estructuras. Si bien el refuerzo a flexión ha sido ampliamente desarrollado y estudiado hasta la fecha, no sucede lo mismo con el refuerzo a cortante, debido principalmente a su gran complejidad. Sin embargo, se debería dedicar más estudio a este tipo de refuerzo si se pretenden conservar los criterios de diseño en estructuras de hormigón armado, los cuales están basados en evitar el fallo a cortante por sus consecuencias catastróficas Esta ausencia de información y de normativa es la que justifica esta tesis doctoral. En este pro-yecto se van a desarrollar dos metodologías alternativas, que permiten estimar la capacidad resistente de vigas de hormigón armado, reforzadas a cortante mediante la técnica FRP-NSM. El primer método aplicado consiste en la implementación de una red neuronal artificial capaz de predecir adecuadamente la resistencia a cortante de vigas reforzadas con este método a partir de experimentos anteriores. Asimismo, a partir de la red se han llevado a cabo algunos estudios a fin de comprender mejor la influencia real de algunos parámetros de la viga y del refuerzo sobre la resistencia a cortante con el propósito de lograr diseños más seguros de este tipo de refuerzo. Una configuración óptima de la red requiere discriminar adecuadamente de entre los numerosos parámetros (geométricos y de material) que pueden influir en el compor-tamiento resistente de la viga, para lo cual se han llevado a cabo diversos estudios y pruebas. Mediante el segundo método, se desarrolla una ecuación de proyecto que permite, de forma sencilla, estimar la capacidad de vigas reforzadas a cortante con FRP-NSM, la cual podría ser propuesta para las principales guías de diseño. Para alcanzar este objetivo, se plantea un pro-blema de optimización multiobjetivo a partir de resultados de ensayos experimentales llevados a cabo sobre vigas de hormigón armado con y sin refuerzo de FRP. El problema multiobjetivo se resuelve mediante algoritmos genéticos, en concreto el algoritmo NSGA-II, por ser más apropiado para problemas con varias funciones objetivo que los métodos de optimización clásicos. Mediante una comparativa de las predicciones realizadas con ambos métodos y de los resulta-dos de ensayos experimentales se podrán establecer las ventajas e inconvenientes derivadas de la aplicación de cada una de las dos metodologías. Asimismo, se llevará a cabo un análisis paramétrico con ambos enfoques a fin de intentar determinar la sensibilidad de aquellos pa-rámetros más sensibles a este tipo de refuerzo. Finalmente, se realizará un análisis estadístico de la fiabilidad de las ecuaciones de diseño deri-vadas de la optimización multiobjetivo. Con dicho análisis se puede estimar la capacidad resis-tente de una viga reforzada a cortante con FRP-NSM dentro de un margen de seguridad espe-cificado a priori. ABSTRACT The use of externally bonded (EB) fibre-reinforced polymer (FRP) composites has gained acceptance during the last two decades in the construction engineering community, particularly in the rehabilitation of reinforced concrete (RC) structures. Currently, to increase the shear resistance of RC beams, FRP sheets are externally bonded (EB-FRP) and applied on the external side surface of the beams to be strengthened with different configurations. Of more recent application, the near-surface mounted FRP bar (NSM-FRP) method is another technique successfully used to increase the shear resistance of RC beams. In the NSM method, FRP rods are embedded into grooves intentionally prepared in the concrete cover of the side faces of RC beams. While flexural strengthening has been widely developed and studied so far, the same doesn´t occur to shearing strength mainly due to its great complexity. Nevertheless, if design criteria are to be preserved more research should be done to this sort of strength, which are based on avoiding shear failure and its catastrophic consequences. However, in spite of this, accurately calculating the shear capacity of FRP shear strengthened RC beams remains a complex challenge that has not yet been fully resolved due to the numerous variables involved in the procedure. The objective of this Thesis is to develop methodologies to evaluate the capacity of FRP shear strengthened RC beams by dealing with the problem from a different point of view to the numerical modeling approach by using artificial intelligence techniques. With this purpose two different approaches have been developed: one concerned with the use of artificial neural networks and the other based on the implementation of an optimization approach developed jointly with the use of artificial neural networks (ANNs) and solved with genetic algorithms (GAs). With these approaches some of the difficulties concerned regarding the numerical modeling can be overcome. As an alternative tool to conventional numerical techniques, neural networks do not provide closed form solutions for modeling problems but do, however, offer a complex and accurate solution based on a representative set of historical examples of the relationship. Furthermore, they can adapt solutions over time to include new data. On the other hand, as a second proposal, an optimization approach has also been developed to implement simple yet accurate shear design equations for this kind of strengthening. This approach is developed in a multi-objective framework by considering experimental results of RC beams with and without NSM-FRP. Furthermore, the results obtained with the previous scheme based on ANNs are also used as a filter to choose the parameters to include in the design equations. Genetic algorithms are used to solve the optimization problem since they are especially suitable for solving multi-objective problems when compared to standard optimization methods. The key features of the two proposed procedures are outlined and their performance in predicting the capacity of NSM-FRP shear strengthened RC beams is evaluated by comparison with results from experimental tests and with predictions obtained using a simplified numerical model. A sensitivity study of the predictions of both models for the input parameters is also carried out.

Manufacturing of self-passivating tungsten based alloys by different powder metallurgical routes

Self-passivating tungsten based alloys will provide a major safety advantage compared to pure tungsten when used as first wall armor of future fusion reactors, due to the formation of a protective oxide layer which prevents the formation of volatile and radioactive WO3 in case of a loss of coolant accident with simultaneous air ingress. Bulk WCr10Ti2 alloys were manufactured by two different powder metallurgical routes: (1) mechanical alloying (MA) followed by hot isostatic pressing (HIP) of metallic capsules, and (2) MA, compaction, pressureless sintering in H2 and subsequent HIPing without encapsulation. Both routes resulted in fully dense materials with homogeneous microstructure and grain sizes of 300 nm and 1 μm, respectively. The content of impurities remained unchanged after HIP, but it increased after sintering due to binder residue. It was not possible to produce large samples by route (2) due to difficulties in the uniaxial compaction stage. Flexural strength and fracture toughness measured on samples produced by route (1) revealed a ductile-to-brittle-transition temperature (DBTT) of about 950 °C. The strength increased from room temperature to 800 °C, decreasing significantly in the plastic region. An increase of fracture toughness is observed around the DBTT.

The effects of tantalum addition on the microtexture and mechanical behaviour of tungsten for ITER applications

Tungsten (W) and its alloys are very promising materials for producing plasma-facing components (PFCs) in the fusion power reactors of the near future, even as a structural part in them. However, whereas the properties of pure tungsten are suitable for a PFC, its structural applications are still limited due to its low toughness, ductile to brittle transition temperature and recrystallization behaviour. Therefore, many efforts have been made to improve its performance by alloying tungsten with other elements. Hence, in this investigation, the thermo-mechanical performance of two new tungsten-tantalum materials has been evaluated. Materials with We5wt.%Ta and We15wt.%Ta were processed by mechanical alloying (MA) and later consolidation by hot isostatic pressing (HIP), with distinct settings for each composition. Thus, it was possible to determine the relationship between the microstructure and the addition of Ta with the macroscopic mechanical properties. These were measured by means of hardness, flexural strength and fracture toughness, in the temperature range of 300e1473 K. The microstructure and the fracture surfaces features of the tested materials were analysed by Field Emission Scanning Electron Microscopy (FESEM).

An antagonistic vascular endothelial growth factor (VEGF) variant inhibits VEGF-stimulated receptor autophosphorylation and proliferation of human endothelial cells

Vascular endothelial growth factor (VEGF) is a potent mitogen with a unique specificity for endothelial cells and a key mediator of aberrant endothelial cell proliferation and vascular permeability in a variety of human pathological situations, such as tumor angiogenesis, diabetic retinopathy, rheumatoid arthritis, or psoriasis. VEGF is a symmetric homodimeric molecule with two receptor binding interfaces lying on each pole of the molecule. Herein we report on the construction and recombinant expression of an asymmetric heterodimeric VEGF variant with an intact receptor binding interface at one pole and a mutant receptor binding interface at the second pole of the dimer. This VEGF variant binds to VEGF receptors but fails to induce receptor activation. In competition experiments, the heterodimeric VEGF variant antagonizes VEGF-stimulated receptor autophosphorylation and proliferation of endothelial cells. A 15-fold excess of the heterodimer was sufficient to inhibit VEGF-stimulated endothelial cell proliferation by 50%, and a 100-fold excess resulted in an almost complete inhibition. By using a rational approach that is based on the structure of VEGF, we have shown the feasibility to construct a VEGF variant that acts as an VEGF antagonist.

A 12R-lipoxygenase in human skin: Mechanistic evidence, molecular cloning, and expression

A recognized feature of psoriasis and other proliferative dermatoses is accumulation in the skin of the unusual arachidonic acid metabolite, 12R-hydroxyeicosatetraenoic acid (12R-HETE). This hydroxy fatty acid is opposite in chirality to the product of the well-known 12S-lipoxygenase and heretofore in mammals is known only as a product of cytochrome P450s. Here we provide mechanistic evidence for a lipoxygenase route to 12R-HETE in human psoriatic tissue and describe a 12R-lipoxygenase that can account for the biosynthesis. Initially we demonstrated retention of the C-12 deuterium of octadeuterated arachidonic acid in its conversion to 12R-HETE in incubations of psoriatic scales, indicating the end product is not formed by isomerization from 12S-H(P)ETE via the 12-keto derivative. Secondly, analysis of product formed from [10R-3H] and [10S-3H]-labeled arachidonic acids revealed that 12R-HETE synthesis is associated with stereospecific removal of the pro-R hydrogen from the 10-carbon of arachidonate. This result is compatible with 12R-lipoxygenase-catalyzed formation of 12R-HETE and not with a P450-catalyzed route to 12R-HETE in psoriatic scales. We cloned a lipoxygenase from human keratinocytes; the cDNA and deduced amino acid sequences share ≤50% identity to other human lipoxygenases. This enzyme, when expressed in Hela cells, oxygenates arachidonic acid to 12-HPETE, >98% 12R in configuration. The 12R-lipoxygenase cDNA is detectable by PCR in psoriatic scales and as a 2.5-kilobase mRNA by Northern analysis of keratinocytes. Identification of this enzyme extends the known distribution of R-lipoxygenases to humans and presents an additional target for potential therapeutic interventions in psoriasis.

Cleavage planes in frog eggs are altered by strong magnetic fields

Early cleavages of Xenopus embryos were oriented in strong, static magnetic fields. Third-cleavage planes, normally horizontal, were seen to orient to a vertical plane parallel with a vertical magnetic field. Second cleavages, normally vertical, could also be oriented by applying a horizontal magnetic field. We argue that these changes in cleavage-furrow geometries result from changes in the orientation of the mitotic apparatus. We hypothesize that the magnetic field acts directly on the microtubules of the mitotic apparatus. Considerations of the length of the astral microtubules, their diamagnetic anisotropy, and flexural rigidity predict the required field strength for an effect that agrees with the data. This observation provides a clear example of a static magnetic-field effect on a fundamental cellular process, cell division.

Identification and characterization of a retinoid-induced class II tumor suppressor/growth regulatory gene

Retinoids, synthetic and natural analogs of retinoic acid, exhibit potent growth inhibitory and cell differentiation activities that account for their beneficial effects in treating hyperproliferative diseases such as psoriasis, actinic keratosis, and certain neoplasias. Tazarotene is a synthetic retinoid that is used in the clinic for the treatment of psoriasis. To better understand the mechanism of retinoid action in the treatment of hyperproliferative diseases, we used a long-range differential display–PCR to isolate retinoid-responsive genes from primary human keratinocytes. We have identified a cDNA, tazarotene-induced gene 3 (TIG3; Retinoic Acid Receptor Responder 3) showing significant homology to the class II tumor suppressor gene, H-rev 107. Tazarotene treatment increases TIG3 expression in primary human keratinocytes and in vivo in psoriatic lesions. Increased TIG3 expression is correlated with decreased proliferation. TIG3 is expressed in a number of tissues, and expression is reduced in cancer cell lines and some primary tumors. In breast cancer cell lines, retinoid-dependent TIG3 induction is observed in lines that are growth suppressed by retinoids but not in nonresponsive lines. Transient over-expression of TIG3 in T47D or Chinese hamster ovary cells inhibits colony expansion. Finally, studies in 293 cells expressing TIG3 linked to an inducible promoter demonstrated decreased proliferation with increased TIG3 levels. These studies suggest that TIG3 may be a growth regulator that mediates some of the growth suppressive effects of retinoids.

Signature p53 mutation at DNA cross-linking sites in 8-methoxypsoralen and ultraviolet A (PUVA)-induced murine skin cancers.

A combination of psoralen and ultraviolet A radiation (PUVA) is widely used in the treatment of psoriasis. However, PUVA treatment increases the risk of developing skin cancer in psoriasis patients and induces skin cancer in mice. Since the DNA damage induced by PUVA is quite different from that induced by UV, we investigated whether PUVA-induced mouse skin cancers display carcinogen-specific mutations in the p53 tumor suppressor gene. The results indicated that 10 of 13 (77%) PUVA-induced skin tumors contained missense mutations predominantly at exons 6 and 7. In contrast, tumor-adjacent, PUVA-exposed skin from tumor-bearing animals did not exhibit p53 mutation in exons 4-8. Interestingly, about 40% of all mutations in PUVA-induced skin tumors occurred at 5'-TA sites, and an equal number of mutations occurred at one base flanking 5'TA or 5'-TAT sites. Since PUVA induces DNA cross-links exclusively at these sites and since UV "signature" mutations were rarely detected in PUVA-induced skin cancers, we can conclude that PUVA acts as a carcinogen by inducing unique PUVA signature mutations in p53. This finding may have implications for identifying the etiology of skin cancer in psoriasis patients who have undergone PUVA therapy.

A polygenic mouse model of psoriasiform skin disease in CD18-deficient mice.

Previously, a hypomorphic mutation in CD18 was generated by gene targeting, with homozygous mice displaying increased circulating neutrophil counts, defects in the response to chemically induced peritonitis, and delays in transplantation rejection. When this mutation was backcrossed onto the PL/J inbred strain, virtually all homozygous mice developed a chronic inflammatory skin disease with a mean age of onset of 11 weeks after birth. The disease was characterized by erythema, hair loss, and the development of scales and crusts. The histopathology revealed hyperplasia of the epidermis, subcorneal microabscesses, orthohyperkeratosis, parakeratosis, and lymphocyte exocytosis, which are features in common with human psoriasis and other hyperproliferative inflammatory skin disorders. Repetitive cultures failed to demonstrate bacterial or fungal organisms potentially involved in the pathogenesis of this disease, and the dermatitis resolved rapidly after subcutaneous administration of dexamethasone. Homozygous mutant mice on a (PL/J x C57BL/6J)F1 background did not develop the disease and backcross experiments suggest that a small number of genes (perhaps as few as one), in addition to CD18, determine susceptibility to the disorder. This phenotype provides a model for inflammatory skin disorders, may have general relevance to polygenic human inflammatory diseases, and should help to identify genes that interact with the beta2 integrins in inflammatory processes.

Estudo de propriedades de resinas compostas bulk fill

Diante da evolução da composição das resinas compostas e do lançamento de compósitos do tipo bulk fill, faz-se necessário o estudo do desempenho dessa nova classe de materiais. Para isso, o presente estudo teve como objetivo avaliar propriedades como grau de conversão (GC) , dureza Knoop (KHN), resistência à flexão (RF) e tenacidade à fratura (KIC) de sete compósitos bulk fill (EverX Posterior, EXP; Filtek Bulk Fill Flow, FBFF; Fill-Up!, FU; SonicFill, SF; Surefil SDR, SDR; Tetric EvoCeram Bulk Fill, TECBF; Venus Bulk Fill, VBF) e um compósito nanohíbrido convencional (Charisma Diamond, CD). De forma complementar, foi realizado tratamento térmico a 170 °C por 10 minutos para melhor compreensão do comportamento desses materiais quanto ao potencial de conversão e à indução de tensões na interface carga/matriz. A avaliação do GC (n=3) foi realizada através de espectroscopia FTIR, a leitura da dureza Knoop foi realizada nas superfícies do topo e da base (n=3), e os ensaios de RF de três pontos (n=10) e KIC (n=10) em máquina de ensaios universais. Os resultados obtidos foram submetidos à analise de variância (complementados pelo teste de Tukey) ou teste Kruskal-Wallis, com nível de significância de 5%. A análise do GC (%) revelou diferença entre os materiais testados, sendo que todas as resinas bulk fill apresentaram valores maiores que a resina convencional: SF (75,7) > VBF (66,7) = EXP (66,4) = SDR (62,8), sendo esta também semelhante a FU (60,0); FU, TECBF (56,6), FBFF (56,6) e CD (54,5) apresentaram conversão semelhante. Os valores de KHN variaram de acordo com o material e com a superfície: apenas SF apresentou KHN semelhante (na superfície do topo) a CD, entretanto não foi possível realizar a leitura da superfície da base deste último material; SF, TECBF e FBFF apresentaram valores de KHN diferentes nas superfícies topo e base; EXP, FU, SDR e VBF mantiveram os valores de dureza do topo semelhantes à superfície da base. Para a RF (MPa), os resultados variaram de acordo com o material: EXP (122,54) = SF (101,09) = CD (99,15), sendo estes dois últimos semelhantes a FU (83,86) e TECBF (82,71), os quais não diferiram da resina SDR (65,18); esta última também mostrou comportamento semelhante a FBFF (60,85) e VBF (59,90). Quanto ao KIC (MPa.mm0,5), EXP (3,35) apresentou o maior valor, semelhante a SF (2,42), que por sua vez também foi igual ao compósito convencional CD (2,01); CD apresentou KIC semelhante a SDR (1,74); SDR = VBF (1,59) = TECBF (1,57); TECBF, FU (1,54) e FBFF (1,37) apresentaram valores semelhantes. Na dependência do material, o tratamento térmico aumentou os valores dos parâmetros estudados, apontando limitações da reação de polimerização dos compósitos estudados. Com base nos resultados obtidos, podese concluir que: resinas bulk fill apresentam elevado GC, superior à resina convencional estudada; a nova classe de materiais restauradores é capaz de polimerizar em profundidade e alguns materiais apresentam KHN semelhantes no topo e na base de espécimes de 4 mm de profundidade; RF e KIC variaram de acordo com o material, e o compósito EXP apresentou os maiores valores para ambos os testes.