An Economic Derivation on Trade Coefficients under the Framework of Multi-regional I-O Analysis

The gravity model, entropy model, potential type model and others like these have been adopted to formulate interregional trade coefficients under the framework of Multi-Regional I-O (MRIO) analysis. Since most of these models are based upon analogies in physics or on statistical principles, they do not provide a theoretical explanation from the view of a firm's or individual's rational and deterministic decision making. In this paper, according to the deterministic choice theory, not only is an alternative formulation of the trade coefficients presented, but also a discussion of an appropriate definition for purchasing prices indices. Since this formulation is consistent with the MRIO system, it can be employed as a useful model-building tool in multi-regional models such as the spatial CGE model.

Pushover analysis for the seismic response prediction of cable-stayed bridges under multi-directional excitation

Cable-stayed bridges represent nowadays key points in transport networks and their seismic behavior needs to be fully understood, even beyond the elastic range of materials. Both nonlinear dynamic (NL-RHA) and static (pushover) procedures are currently available to face this challenge, each with intrinsic advantages and disadvantages, and their applicability in the study of the nonlinear seismic behavior of cable-stayed bridges is discussed here. The seismic response of a large number of finite element models with different span lengths, tower shapes and class of foundation soil is obtained with different procedures and compared. Several features of the original Modal Pushover Analysis (MPA) are modified in light of cable-stayed bridge characteristics, furthermore, an extension of MPA and a new coupled pushover analysis (CNSP) are suggested to estimate the complex inelastic response of such outstanding structures subjected to multi-axial strong ground motions.

The use of direct boundary element method for gaining insight into complex seismic site response

The boundary element method is specially well suited for the analysis of the seismic response of valleys of complicated topography and stratigraphy. In this paper the method’s capabilities are illustrated using as an example an irregularity stratified (test site) sedimentary basin that has been modelled using 2D discretization and the Direct Boundary Element Method (DBEM). Site models displaying different levels of complexity are used in practice. The multi-layered model’s seismic response shows generally good agreement with observed data amplification levels, fundamental frequencies and the high spatial variability. Still important features such as the location of high frequencies peaks are missing. Even 2D simplified models reveal important characteristics of the wave field that 1D modelling does not show up.

Analysis and optimized design of a distributed multi-stage EMC filter for an interleaved three-phase PWM-rectifier system for aircraft applications

Different possible input filter configurations for a modular three-phase PWM rectifier system consisting of three interleaved converter cells are studied. The system is designed for an aircraft application where MIL-STD-461E conducted EMI standards have to be met and system weight is a critical design issue. The importance of a LISN model on the simulated noise levels and the effect of interleaving and power unbalance between the different converter modules is discussed. The effect of the number of filter stages and the degree of distribution of the filter stages among the individual converter modules on the weight and losses of the input filter is studied and optimal filter structures are proposed.

A fuzzy MCDA framework for safety assessment in the remediation of a uranium mill tailings site in Ukraine

The Pridneprovsky Chemical Plant was one of the largest uranium processing enterprises in the former USSR, producing a huge amount of uranium residues. The Zapadnoe tailings site contains most of these residues. We propose a theoretical framework based on multicriteria decision analysis and fuzzy logic to analyze different remediation alternatives for the Zapadnoe tailings, which simultaneously accounts for potentially conflicting economic, social and environmental objectives. We build an objective hierarchy that includes all the relevant aspects. Fuzzy rather than precise values are proposed for use to evaluate remediation alternatives against the different criteria and to quantify preferences, such as the weights representing the relative importance of criteria identified in the objective hierarchy. Finally, we suggest that remediation alternatives should be evaluated by means of a fuzzy additive multi-attribute utility function and ranked on the basis of the respective trapezoidal fuzzy number representing their overall utility.

Bayesian scene analysis for multi-camera 3D tracking and camera positioning

Los sistemas de seguimiento mono-cámara han demostrado su notable capacidad para el análisis de trajectorias de objectos móviles y para monitorización de escenas de interés; sin embargo, tanto su robustez como sus posibilidades en cuanto a comprensión semántica de la escena están fuertemente limitadas por su naturaleza local y monocular, lo que los hace insuficientes para aplicaciones realistas de videovigilancia. El objetivo de esta tesis es la extensión de las posibilidades de los sistemas de seguimiento de objetos móviles para lograr un mayor grado de robustez y comprensión de la escena. La extensión propuesta se divide en dos direcciones separadas. La primera puede considerarse local, ya que está orientada a la mejora y enriquecimiento de las posiciones estimadas para los objetos móviles observados directamente por las cámaras del sistema; dicha extensión se logra mediante el desarrollo de un sistema multi-cámara de seguimiento 3D, capaz de proporcionar consistentemente las posiciones 3D de múltiples objetos a partir de las observaciones capturadas por un conjunto de sensores calibrados y con campos de visión solapados. La segunda extensión puede considerarse global, dado que su objetivo consiste en proporcionar un contexto global para relacionar las observaciones locales realizadas por una cámara con una escena de mucho mayor tamaño; para ello se propone un sistema automático de localización de cámaras basado en las trayectorias observadas de varios objetos móviles y en un mapa esquemático de la escena global monitorizada. Ambas líneas de investigación se tratan utilizando, como marco común, técnicas de estimación bayesiana: esta elección está justificada por la versatilidad y flexibilidad proporcionada por dicho marco estadístico, que permite la combinación natural de múltiples fuentes de información sobre los parámetros a estimar, así como un tratamiento riguroso de la incertidumbre asociada a las mismas mediante la inclusión de modelos de observación específicamente diseñados. Además, el marco seleccionado abre grandes posibilidades operacionales, puesto que permite la creación de diferentes métodos numéricos adaptados a las necesidades y características específicas de distintos problemas tratados. El sistema de seguimiento 3D con múltiples cámaras propuesto está específicamente diseñado para permitir descripciones esquemáticas de las medidas realizadas individualmente por cada una de las cámaras del sistema: esta elección de diseño, por tanto, no asume ningún algoritmo específico de detección o seguimiento 2D en ninguno de los sensores de la red, y hace que el sistema propuesto sea aplicable a redes reales de vigilancia con capacidades limitadas tanto en términos de procesamiento como de transmision. La combinación robusta de las observaciones capturadas individualmente por las cámaras, ruidosas, incompletas y probablemente contaminadas por falsas detecciones, se basa en un metodo de asociación bayesiana basado en geometría y color: los resultados de dicha asociación permiten el seguimiento 3D de los objetos de la escena mediante el uso de un filtro de partículas. El sistema de fusión de observaciones propuesto tiene, como principales características, una gran precisión en términos de localización 3D de objetos, y una destacable capacidad de recuperación tras eventuales errores debidos a un número insuficiente de datos de entrada. El sistema automático de localización de cámaras se basa en la observación de múltiples objetos móviles y un mapa esquemático de las áreas transitables del entorno monitorizado para inferir la posición absoluta de dicho sensor. Para este propósito, se propone un novedoso marco bayesiano que combina modelos dinámicos inducidos por el mapa en los objetos móviles presentes en la escena con las trayectorias observadas por la cámara, lo que representa un enfoque nunca utilizado en la literatura existente. El sistema de localización se divide en dos sub-tareas diferenciadas, debido a que cada una de estas tareas requiere del diseño de algoritmos específicos de muestreo para explotar en profundidad las características del marco desarrollado: por un lado, análisis de la ambigüedad del caso específicamente tratado y estimación aproximada de la localización de la cámara, y por otro, refinado de la localización de la cámara. El sistema completo, diseñado y probado para el caso específico de localización de cámaras en entornos de tráfico urbano, podría tener aplicación también en otros entornos y sensores de diferentes modalidades tras ciertas adaptaciones. ABSTRACT Mono-camera tracking systems have proved their capabilities for moving object trajectory analysis and scene monitoring, but their robustness and semantic possibilities are strongly limited by their local and monocular nature and are often insufficient for realistic surveillance applications. This thesis is aimed at extending the possibilities of moving object tracking systems to a higher level of scene understanding. The proposed extension comprises two separate directions. The first one is local, since is aimed at enriching the inferred positions of the moving objects within the area of the monitored scene directly covered by the cameras of the system; this task is achieved through the development of a multi-camera system for robust 3D tracking, able to provide 3D tracking information of multiple simultaneous moving objects from the observations reported by a set of calibrated cameras with semi-overlapping fields of view. The second extension is global, as is aimed at providing local observations performed within the field of view of one camera with a global context relating them to a much larger scene; to this end, an automatic camera positioning system relying only on observed object trajectories and a scene map is designed. The two lines of research in this thesis are addressed using Bayesian estimation as a general unifying framework. Its suitability for these two applications is justified by the flexibility and versatility of that stochastic framework, which allows the combination of multiple sources of information about the parameters to estimate in a natural and elegant way, addressing at the same time the uncertainty associated to those sources through the inclusion of models designed to this end. In addition, it opens multiple possibilities for the creation of different numerical methods for achieving satisfactory and efficient practical solutions to each addressed application. The proposed multi-camera 3D tracking method is specifically designed to work on schematic descriptions of the observations performed by each camera of the system: this choice allows the use of unspecific off-the-shelf 2D detection and/or tracking subsystems running independently at each sensor, and makes the proposal suitable for real surveillance networks with moderate computational and transmission capabilities. The robust combination of such noisy, incomplete and possibly unreliable schematic descriptors relies on a Bayesian association method, based on geometry and color, whose results allow the tracking of the targets in the scene with a particle filter. The main features exhibited by the proposal are, first, a remarkable accuracy in terms of target 3D positioning, and second, a great recovery ability after tracking losses due to insufficient input data. The proposed system for visual-based camera self-positioning uses the observations of moving objects and a schematic map of the passable areas of the environment to infer the absolute sensor position. To this end, a new Bayesian framework combining trajectory observations and map-induced dynamic models for moving objects is designed, which represents an approach to camera positioning never addressed before in the literature. This task is divided into two different sub-tasks, setting ambiguity analysis and approximate position estimation, on the one hand, and position refining, on the other, since they require the design of specific sampling algorithms to correctly exploit the discriminative features of the developed framework. This system, designed for camera positioning and demonstrated in urban traffic environments, can also be applied to different environments and sensors of other modalities after certain required adaptations.

Bayesian scene analysis for multi-camera 3D tracking and camera positioning

Los sistemas de seguimiento mono-cámara han demostrado su notable capacidad para el análisis de trajectorias de objectos móviles y para monitorización de escenas de interés; sin embargo, tanto su robustez como sus posibilidades en cuanto a comprensión semántica de la escena están fuertemente limitadas por su naturaleza local y monocular, lo que los hace insuficientes para aplicaciones realistas de videovigilancia. El objetivo de esta tesis es la extensión de las posibilidades de los sistemas de seguimiento de objetos móviles para lograr un mayor grado de robustez y comprensión de la escena. La extensión propuesta se divide en dos direcciones separadas. La primera puede considerarse local, ya que está orientada a la mejora y enriquecimiento de las posiciones estimadas para los objetos móviles observados directamente por las cámaras del sistema; dicha extensión se logra mediante el desarrollo de un sistema multi-cámara de seguimiento 3D, capaz de proporcionar consistentemente las posiciones 3D de múltiples objetos a partir de las observaciones capturadas por un conjunto de sensores calibrados y con campos de visión solapados. La segunda extensión puede considerarse global, dado que su objetivo consiste en proporcionar un contexto global para relacionar las observaciones locales realizadas por una cámara con una escena de mucho mayor tamaño; para ello se propone un sistema automático de localización de cámaras basado en las trayectorias observadas de varios objetos móviles y en un mapa esquemático de la escena global monitorizada. Ambas líneas de investigación se tratan utilizando, como marco común, técnicas de estimación bayesiana: esta elección está justificada por la versatilidad y flexibilidad proporcionada por dicho marco estadístico, que permite la combinación natural de múltiples fuentes de información sobre los parámetros a estimar, así como un tratamiento riguroso de la incertidumbre asociada a las mismas mediante la inclusión de modelos de observación específicamente diseñados. Además, el marco seleccionado abre grandes posibilidades operacionales, puesto que permite la creación de diferentes métodos numéricos adaptados a las necesidades y características específicas de distintos problemas tratados. El sistema de seguimiento 3D con múltiples cámaras propuesto está específicamente diseñado para permitir descripciones esquemáticas de las medidas realizadas individualmente por cada una de las cámaras del sistema: esta elección de diseño, por tanto, no asume ningún algoritmo específico de detección o seguimiento 2D en ninguno de los sensores de la red, y hace que el sistema propuesto sea aplicable a redes reales de vigilancia con capacidades limitadas tanto en términos de procesamiento como de transmision. La combinación robusta de las observaciones capturadas individualmente por las cámaras, ruidosas, incompletas y probablemente contaminadas por falsas detecciones, se basa en un metodo de asociación bayesiana basado en geometría y color: los resultados de dicha asociación permiten el seguimiento 3D de los objetos de la escena mediante el uso de un filtro de partículas. El sistema de fusión de observaciones propuesto tiene, como principales características, una gran precisión en términos de localización 3D de objetos, y una destacable capacidad de recuperación tras eventuales errores debidos a un número insuficiente de datos de entrada. El sistema automático de localización de cámaras se basa en la observación de múltiples objetos móviles y un mapa esquemático de las áreas transitables del entorno monitorizado para inferir la posición absoluta de dicho sensor. Para este propósito, se propone un novedoso marco bayesiano que combina modelos dinámicos inducidos por el mapa en los objetos móviles presentes en la escena con las trayectorias observadas por la cámara, lo que representa un enfoque nunca utilizado en la literatura existente. El sistema de localización se divide en dos sub-tareas diferenciadas, debido a que cada una de estas tareas requiere del diseño de algoritmos específicos de muestreo para explotar en profundidad las características del marco desarrollado: por un lado, análisis de la ambigüedad del caso específicamente tratado y estimación aproximada de la localización de la cámara, y por otro, refinado de la localización de la cámara. El sistema completo, diseñado y probado para el caso específico de localización de cámaras en entornos de tráfico urbano, podría tener aplicación también en otros entornos y sensores de diferentes modalidades tras ciertas adaptaciones. ABSTRACT Mono-camera tracking systems have proved their capabilities for moving object trajectory analysis and scene monitoring, but their robustness and semantic possibilities are strongly limited by their local and monocular nature and are often insufficient for realistic surveillance applications. This thesis is aimed at extending the possibilities of moving object tracking systems to a higher level of scene understanding. The proposed extension comprises two separate directions. The first one is local, since is aimed at enriching the inferred positions of the moving objects within the area of the monitored scene directly covered by the cameras of the system; this task is achieved through the development of a multi-camera system for robust 3D tracking, able to provide 3D tracking information of multiple simultaneous moving objects from the observations reported by a set of calibrated cameras with semi-overlapping fields of view. The second extension is global, as is aimed at providing local observations performed within the field of view of one camera with a global context relating them to a much larger scene; to this end, an automatic camera positioning system relying only on observed object trajectories and a scene map is designed. The two lines of research in this thesis are addressed using Bayesian estimation as a general unifying framework. Its suitability for these two applications is justified by the flexibility and versatility of that stochastic framework, which allows the combination of multiple sources of information about the parameters to estimate in a natural and elegant way, addressing at the same time the uncertainty associated to those sources through the inclusion of models designed to this end. In addition, it opens multiple possibilities for the creation of different numerical methods for achieving satisfactory and efficient practical solutions to each addressed application. The proposed multi-camera 3D tracking method is specifically designed to work on schematic descriptions of the observations performed by each camera of the system: this choice allows the use of unspecific off-the-shelf 2D detection and/or tracking subsystems running independently at each sensor, and makes the proposal suitable for real surveillance networks with moderate computational and transmission capabilities. The robust combination of such noisy, incomplete and possibly unreliable schematic descriptors relies on a Bayesian association method, based on geometry and color, whose results allow the tracking of the targets in the scene with a particle filter. The main features exhibited by the proposal are, first, a remarkable accuracy in terms of target 3D positioning, and second, a great recovery ability after tracking losses due to insufficient input data. The proposed system for visual-based camera self-positioning uses the observations of moving objects and a schematic map of the passable areas of the environment to infer the absolute sensor position. To this end, a new Bayesian framework combining trajectory observations and map-induced dynamic models for moving objects is designed, which represents an approach to camera positioning never addressed before in the literature. This task is divided into two different sub-tasks, setting ambiguity analysis and approximate position estimation, on the one hand, and position refining, on the other, since they require the design of specific sampling algorithms to correctly exploit the discriminative features of the developed framework. This system, designed for camera positioning and demonstrated in urban traffic environments, can also be applied to different environments and sensors of other modalities after certain required adaptations.

Methods for the analysis of multi-scale cell dynamics from fluorescence microscopy images

La embriogénesis es el proceso mediante el cual una célula se convierte en un ser un vivo. A lo largo de diferentes etapas de desarrollo, la población de células va proliferando a la vez que el embrión va tomando forma y se configura. Esto es posible gracias a la acción de varios procesos genéticos, bioquímicos y mecánicos que interaccionan y se regulan entre ellos formando un sistema complejo que se organiza a diferentes escalas espaciales y temporales. Este proceso ocurre de manera robusta y reproducible, pero también con cierta variabilidad que permite la diversidad de individuos de una misma especie. La aparición de la microscopía de fluorescencia, posible gracias a proteínas fluorescentes que pueden ser adheridas a las cadenas de expresión de las células, y los avances en la física óptica de los microscopios han permitido observar este proceso de embriogénesis in-vivo y generar secuencias de imágenes tridimensionales de alta resolución espacio-temporal. Estas imágenes permiten el estudio de los procesos de desarrollo embrionario con técnicas de análisis de imagen y de datos, reconstruyendo dichos procesos para crear la representación de un embrión digital. Una de las más actuales problemáticas en este campo es entender los procesos mecánicos, de manera aislada y en interacción con otros factores como la expresión genética, para que el embrión se desarrolle. Debido a la complejidad de estos procesos, estos problemas se afrontan mediante diferentes técnicas y escalas específicas donde, a través de experimentos, pueden hacerse y confrontarse hipótesis, obteniendo conclusiones sobre el funcionamiento de los mecanismos estudiados. Esta tesis doctoral se ha enfocado sobre esta problemática intentando mejorar las metodologías del estado del arte y con un objetivo específico: estudiar patrones de deformación que emergen del movimiento organizado de las células durante diferentes estados del desarrollo del embrión, de manera global o en tejidos concretos. Estudios se han centrado en la mecánica en relación con procesos de señalización o interacciones a nivel celular o de tejido. En este trabajo, se propone un esquema para generalizar el estudio del movimiento y las interacciones mecánicas que se desprenden del mismo a diferentes escalas espaciales y temporales. Esto permitiría no sólo estudios locales, si no estudios sistemáticos de las escalas de interacción mecánica dentro de un embrión. Por tanto, el esquema propuesto obvia las causas de generación de movimiento (fuerzas) y se centra en la cuantificación de la cinemática (deformación y esfuerzos) a partir de imágenes de forma no invasiva. Hoy en día las dificultades experimentales y metodológicas y la complejidad de los sistemas biológicos impiden una descripción mecánica completa de manera sistemática. Sin embargo, patrones de deformación muestran el resultado de diferentes factores mecánicos en interacción con otros elementos dando lugar a una organización mecánica, necesaria para el desarrollo, que puede ser cuantificado a partir de la metodología propuesta en esta tesis. La metodología asume un medio continuo descrito de forma Lagrangiana (en función de las trayectorias de puntos materiales que se mueven en el sistema en lugar de puntos espaciales) de la dinámica del movimiento, estimado a partir de las imágenes mediante métodos de seguimiento de células o de técnicas de registro de imagen. Gracias a este esquema es posible describir la deformación instantánea y acumulada respecto a un estado inicial para cualquier dominio del embrión. La aplicación de esta metodología a imágenes 3D + t del pez zebra sirvió para desvelar estructuras mecánicas que tienden a estabilizarse a lo largo del tiempo en dicho embrión, y que se organizan a una escala semejante al del mapa de diferenciación celular y con indicios de correlación con patrones de expresión genética. También se aplicó la metodología al estudio del tejido amnioserosa de la Drosophila (mosca de la fruta) durante el cierre dorsal, obteniendo indicios de un acoplamiento entre escalas subcelulares, celulares y supracelulares, que genera patrones complejos en respuesta a la fuerza generada por los esqueletos de acto-myosina. En definitiva, esta tesis doctoral propone una estrategia novedosa de análisis de la dinámica celular multi-escala que permite cuantificar patrones de manera inmediata y que además ofrece una representación que reconstruye la evolución de los procesos como los ven las células, en lugar de como son observados desde el microscopio. Esta metodología por tanto permite nuevas formas de análisis y comparación de embriones y tejidos durante la embriogénesis a partir de imágenes in-vivo. ABSTRACT The embryogenesis is the process from which a single cell turns into a living organism. Through several stages of development, the cell population proliferates at the same time the embryo shapes and the organs develop gaining their functionality. This is possible through genetic, biochemical and mechanical factors that are involved in a complex interaction of processes organized in different levels and in different spatio-temporal scales. The embryogenesis, through this complexity, develops in a robust and reproducible way, but allowing variability that makes possible the diversity of living specimens. The advances in physics of microscopes and the appearance of fluorescent proteins that can be attached to expression chains, reporting about structural and functional elements of the cell, have enabled for the in-vivo observation of embryogenesis. The imaging process results in sequences of high spatio-temporal resolution 3D+time data of the embryogenesis as a digital representation of the embryos that can be further analyzed, provided new image processing and data analysis techniques are developed. One of the most relevant and challenging lines of research in the field is the quantification of the mechanical factors and processes involved in the shaping process of the embryo and their interactions with other embryogenesis factors such as genetics. Due to the complexity of the processes, studies have focused on specific problems and scales controlled in the experiments, posing and testing hypothesis to gain new biological insight. However, methodologies are often difficult to be exported to study other biological phenomena or specimens. This PhD Thesis is framed within this paradigm of research and tries to propose a systematic methodology to quantify the emergent deformation patterns from the motion estimated in in-vivo images of embryogenesis. Thanks to this strategy it would be possible to quantify not only local mechanisms, but to discover and characterize the scales of mechanical organization within the embryo. The framework focuses on the quantification of the motion kinematics (deformation and strains), neglecting the causes of the motion (forces), from images in a non-invasive way. Experimental and methodological challenges hamper the quantification of exerted forces and the mechanical properties of tissues. However, a descriptive framework of deformation patterns provides valuable insight about the organization and scales of the mechanical interactions, along the embryo development. Such a characterization would help to improve mechanical models and progressively understand the complexity of embryogenesis. This framework relies on a Lagrangian representation of the cell dynamics system based on the trajectories of points moving along the deformation. This approach of analysis enables the reconstruction of the mechanical patterning as experienced by the cells and tissues. Thus, we can build temporal profiles of deformation along stages of development, comprising both the instantaneous events and the cumulative deformation history. The application of this framework to 3D + time data of zebrafish embryogenesis allowed us to discover mechanical profiles that stabilized through time forming structures that organize in a scale comparable to the map of cell differentiation (fate map), and also suggesting correlation with genetic patterns. The framework was also applied to the analysis of the amnioserosa tissue in the drosophila’s dorsal closure, revealing that the oscillatory contraction triggered by the acto-myosin network organized complexly coupling different scales: local force generation foci, cellular morphology control mechanisms and tissue geometrical constraints. In summary, this PhD Thesis proposes a theoretical framework for the analysis of multi-scale cell dynamics that enables to quantify automatically mechanical patterns and also offers a new representation of the embryo dynamics as experienced by cells instead of how the microscope captures instantaneously the processes. Therefore, this framework enables for new strategies of quantitative analysis and comparison between embryos and tissues during embryogenesis from in-vivo images.

State space models for multi-setup operational modal analysis

Operational Modal Analysis consists on estimate the modal parameters of a structure (natural frequencies, damping ratios and modal vectors) from output-only vibration measurements. The modal vectors can be only estimated where a sensor is placed, so when the number of available sensors is lower than the number of tested points, it is usual to perform several tests changing the position of the sensors from one test to the following (multiple setups of sensors): some sensors stay at the same position from setup to setup, and the other sensors change the position until all the tested points are covered. The permanent sensors are then used to merge the mode shape estimated at each setup (or partial modal vectors) into global modal vectors. Traditionally, the partial modal vectors are estimated independently setup by setup, and the global modal vectors are obtained in a postprocess phase. In this work we present two state space models that can be used to process all the recorded setups at the same time, and we also present how these models can be estimated using the maximum likelihood method. The result is that the global mode shape of each mode is obtained automatically, and subsequently, a single value for the natural frequency and damping ratio of the mode is computed. Finally, both models are compared using real measured data.

Effect of type of fiber, site of fermentation, and method of analysis on digestibility of soluble and insoluble fiber in rabbits

The effect of type of fiber, site of fermetation, method for quantifying insoluble and soluble dietary fiber, and their correction for intestinal mucin on fiber digestibility were examined in rabbits. Three diets differing in soluble fiber were formulated (8.5% soluble fiber, on DM basis, in the low soluble fiber [LSF] diet; 10.2% in the medium soluble fiber [MSF] diet; and 14.5% in the high soluble fiber [HSF] diet). They were obtained by replacing half of the dehydrated alfalfa in the MSF diet with a mixture of beet and apple pulp (HSF diet) or with a mix of oat hulls and soybean protein (LSF diet). Thirty rabbits with ileal T-cannulas were used to determine ileal and fecal digestibility. Cecal digestibility was determined by difference between fecal and ileal digestibility. Insoluble fiber was measured as NDF, insoluble dietary fiber (IDF), and in vitro insoluble fiber, whereas soluble fiber was calculated as the difference between total dietary fiber (TDF) and NDF (TDF_NDF), IDF (TDF-IDF), and in vitro insoluble fiber (TDF-in vitro insoluble fiber). The intestinal mucin content was used to correct the TDF and soluble fiber digestibility. Ileal and fecal concentration of mucin increased from the LSF to the HSF diet group (P < 0.01). Once corrected for intestinal mucin, ileal and fecal digestibility of TDF and soluble fiber increased whereas cecal digestibility decreased (P < 0.01). Ileal digestibility of TDF increased from the LSF to the HSF diet group (12.0 vs. 28.1%; P < 0.01), with no difference in the cecum (26.4%), resulting in a higher fecal digestibility from the LSF to the HSF diet group (P < 0.01). Ileal digestibility of insoluble fiber increased from the LSF to the HSF diet group (11.3 vs. 21.0%; P < 0.01), with no difference in the cecum (13.9%) and no effect of fiber method, resulting in a higher fecal digestibility for rabbits fed the HSF diet compared with the MSF and LSF diets groups (P < 0.01).Fecal digestibility of NDF was higher compared with IDF or in vitro insoluble fiber (P < 0.01). Ileal soluble fiber digestibility was higher for the HSF than for the LSF diet group (43.6 vs. 14.5%; P < 0.01) and fiber method did not affect it. Cecal soluble fiber digestibility decreased from the LSF to the HSF diet group (72.1 vs. 49.2%; P < 0.05). The lowest cecal and fecal soluble fiber digestibility was measured using TDF-NDF (P < 0.01). In conclusion, a correction for intestinal mucin is necessary for ileal TDF and soluble fiber digestibility whereas the selection of the fiber method has a minor relevance. The inclusion of sugar beet and apple pulp increased the amount of TDF fermented in the small intestine.

Automated wordlength optimization framework for multi-source statistical interval-based analysis of nonlinear systems with control-flow structures

El uso de aritmética de punto fijo es una opción de diseño muy extendida en sistemas con fuertes restricciones de área, consumo o rendimiento. Para producir implementaciones donde los costes se minimicen sin impactar negativamente en la precisión de los resultados debemos llevar a cabo una asignación cuidadosa de anchuras de palabra. Encontrar la combinación óptima de anchuras de palabra en coma fija para un sistema dado es un problema combinatorio NP-hard al que los diseñadores dedican entre el 25 y el 50 % del ciclo de diseño. Las plataformas hardware reconfigurables, como son las FPGAs, también se benefician de las ventajas que ofrece la aritmética de coma fija, ya que éstas compensan las frecuencias de reloj más bajas y el uso más ineficiente del hardware que hacen estas plataformas respecto a los ASICs. A medida que las FPGAs se popularizan para su uso en computación científica los diseños aumentan de tamaño y complejidad hasta llegar al punto en que no pueden ser manejados eficientemente por las técnicas actuales de modelado de señal y ruido de cuantificación y de optimización de anchura de palabra. En esta Tesis Doctoral exploramos distintos aspectos del problema de la cuantificación y presentamos nuevas metodologías para cada uno de ellos: Las técnicas basadas en extensiones de intervalos han permitido obtener modelos de propagación de señal y ruido de cuantificación muy precisos en sistemas con operaciones no lineales. Nosotros llevamos esta aproximación un paso más allá introduciendo elementos de Multi-Element Generalized Polynomial Chaos (ME-gPC) y combinándolos con una técnica moderna basada en Modified Affine Arithmetic (MAA) estadístico para así modelar sistemas que contienen estructuras de control de flujo. Nuestra metodología genera los distintos caminos de ejecución automáticamente, determina las regiones del dominio de entrada que ejercitarán cada uno de ellos y extrae los momentos estadísticos del sistema a partir de dichas soluciones parciales. Utilizamos esta técnica para estimar tanto el rango dinámico como el ruido de redondeo en sistemas con las ya mencionadas estructuras de control de flujo y mostramos la precisión de nuestra aproximación, que en determinados casos de uso con operadores no lineales llega a tener tan solo una desviación del 0.04% con respecto a los valores de referencia obtenidos mediante simulación. Un inconveniente conocido de las técnicas basadas en extensiones de intervalos es la explosión combinacional de términos a medida que el tamaño de los sistemas a estudiar crece, lo cual conlleva problemas de escalabilidad. Para afrontar este problema presen tamos una técnica de inyección de ruidos agrupados que hace grupos con las señales del sistema, introduce las fuentes de ruido para cada uno de los grupos por separado y finalmente combina los resultados de cada uno de ellos. De esta forma, el número de fuentes de ruido queda controlado en cada momento y, debido a ello, la explosión combinatoria se minimiza. También presentamos un algoritmo de particionado multi-vía destinado a minimizar la desviación de los resultados a causa de la pérdida de correlación entre términos de ruido con el objetivo de mantener los resultados tan precisos como sea posible. La presente Tesis Doctoral también aborda el desarrollo de metodologías de optimización de anchura de palabra basadas en simulaciones de Monte-Cario que se ejecuten en tiempos razonables. Para ello presentamos dos nuevas técnicas que exploran la reducción del tiempo de ejecución desde distintos ángulos: En primer lugar, el método interpolativo aplica un interpolador sencillo pero preciso para estimar la sensibilidad de cada señal, y que es usado después durante la etapa de optimización. En segundo lugar, el método incremental gira en torno al hecho de que, aunque es estrictamente necesario mantener un intervalo de confianza dado para los resultados finales de nuestra búsqueda, podemos emplear niveles de confianza más relajados, lo cual deriva en un menor número de pruebas por simulación, en las etapas iniciales de la búsqueda, cuando todavía estamos lejos de las soluciones optimizadas. Mediante estas dos aproximaciones demostramos que podemos acelerar el tiempo de ejecución de los algoritmos clásicos de búsqueda voraz en factores de hasta x240 para problemas de tamaño pequeño/mediano. Finalmente, este libro presenta HOPLITE, una infraestructura de cuantificación automatizada, flexible y modular que incluye la implementación de las técnicas anteriores y se proporciona de forma pública. Su objetivo es ofrecer a desabolladores e investigadores un entorno común para prototipar y verificar nuevas metodologías de cuantificación de forma sencilla. Describimos el flujo de trabajo, justificamos las decisiones de diseño tomadas, explicamos su API pública y hacemos una demostración paso a paso de su funcionamiento. Además mostramos, a través de un ejemplo sencillo, la forma en que conectar nuevas extensiones a la herramienta con las interfaces ya existentes para poder así expandir y mejorar las capacidades de HOPLITE. ABSTRACT Using fixed-point arithmetic is one of the most common design choices for systems where area, power or throughput are heavily constrained. In order to produce implementations where the cost is minimized without negatively impacting the accuracy of the results, a careful assignment of word-lengths is required. The problem of finding the optimal combination of fixed-point word-lengths for a given system is a combinatorial NP-hard problem to which developers devote between 25 and 50% of the design-cycle time. Reconfigurable hardware platforms such as FPGAs also benefit of the advantages of fixed-point arithmetic, as it compensates for the slower clock frequencies and less efficient area utilization of the hardware platform with respect to ASICs. As FPGAs become commonly used for scientific computation, designs constantly grow larger and more complex, up to the point where they cannot be handled efficiently by current signal and quantization noise modelling and word-length optimization methodologies. In this Ph.D. Thesis we explore different aspects of the quantization problem and we present new methodologies for each of them: The techniques based on extensions of intervals have allowed to obtain accurate models of the signal and quantization noise propagation in systems with non-linear operations. We take this approach a step further by introducing elements of MultiElement Generalized Polynomial Chaos (ME-gPC) and combining them with an stateof- the-art Statistical Modified Affine Arithmetic (MAA) based methodology in order to model systems that contain control-flow structures. Our methodology produces the different execution paths automatically, determines the regions of the input domain that will exercise them, and extracts the system statistical moments from the partial results. We use this technique to estimate both the dynamic range and the round-off noise in systems with the aforementioned control-flow structures. We show the good accuracy of our approach, which in some case studies with non-linear operators shows a 0.04 % deviation respect to the simulation-based reference values. A known drawback of the techniques based on extensions of intervals is the combinatorial explosion of terms as the size of the targeted systems grows, which leads to scalability problems. To address this issue we present a clustered noise injection technique that groups the signals in the system, introduces the noise terms in each group independently and then combines the results at the end. In this way, the number of noise sources in the system at a given time is controlled and, because of this, the combinato rial explosion is minimized. We also present a multi-way partitioning algorithm aimed at minimizing the deviation of the results due to the loss of correlation between noise terms, in order to keep the results as accurate as possible. This Ph.D. Thesis also covers the development of methodologies for word-length optimization based on Monte-Carlo simulations in reasonable times. We do so by presenting two novel techniques that explore the reduction of the execution times approaching the problem in two different ways: First, the interpolative method applies a simple but precise interpolator to estimate the sensitivity of each signal, which is later used to guide the optimization effort. Second, the incremental method revolves on the fact that, although we strictly need to guarantee a certain confidence level in the simulations for the final results of the optimization process, we can do it with more relaxed levels, which in turn implies using a considerably smaller amount of samples, in the initial stages of the process, when we are still far from the optimized solution. Through these two approaches we demonstrate that the execution time of classical greedy techniques can be accelerated by factors of up to ×240 for small/medium sized problems. Finally, this book introduces HOPLITE, an automated, flexible and modular framework for quantization that includes the implementation of the previous techniques and is provided for public access. The aim is to offer a common ground for developers and researches for prototyping and verifying new techniques for system modelling and word-length optimization easily. We describe its work flow, justifying the taken design decisions, explain its public API and we do a step-by-step demonstration of its execution. We also show, through an example, the way new extensions to the flow should be connected to the existing interfaces in order to expand and improve the capabilities of HOPLITE.

Temperature and precipitation effects on wheat yield across a European transect: a crop model ensemble analysis using impact response surfaces

This study explored the utility of the impact response surface (IRS) approach for investigating model ensemble crop yield responses under a large range of changes in climate. IRSs of spring and winter wheat Triticum aestivum yields were constructed from a 26-member ensemble of process-based crop simulation models for sites in Finland, Germany and Spain across a latitudinal transect. The sensitivity of modelled yield to systematic increments of changes in temperature (-2 to +9°C) and precipitation (-50 to +50%) was tested by modifying values of baseline (1981 to 2010) daily weather, with CO2 concentration fixed at 360 ppm. The IRS approach offers an effective method of portraying model behaviour under changing climate as well as advantages for analysing, comparing and presenting results from multi-model ensemble simulations. Though individual model behaviour occasionally departed markedly from the average, ensemble median responses across sites and crop varieties indicated that yields decline with higher temperatures and decreased precipitation and increase with higher precipitation. Across the uncertainty ranges defined for the IRSs, yields were more sensitive to temperature than precipitation changes at the Finnish site while sensitivities were mixed at the German and Spanish sites. Precipitation effects diminished under higher temperature changes. While the bivariate and multi-model characteristics of the analysis impose some limits to interpretation, the IRS approach nonetheless provides additional insights into sensitivities to inter-model and inter-annual variability. Taken together, these sensitivities may help to pinpoint processes such as heat stress, vernalisation or drought effects requiring refinement in future model development.

Analysis of human cytochrome P450 3A4 cooperativity: Construction and characterization of a site-directed mutant that displays hyperbolic steroid hydroxylation kinetics

Cytochrome P450 3A4 is generally considered to be the most important human drug-metabolizing enzyme and is known to catalyze the oxidation of a number of substrates in a cooperative manner. An allosteric mechanism is usually invoked to explain the cooperativity. Based on a structure–activity study from another laboratory using various effector–substrate combinations and on our own studies using site-directed mutagenesis and computer modeling of P450 3A4, the most likely location of effector binding is in the active site along with the substrate. Our study was designed to test this hypothesis by replacing residues Leu-211 and Asp-214 with the larger Phe and Glu, respectively. These residues were predicted to constitute a portion of the effector binding site, and the substitutions were designed to mimic the action of the effector by reducing the size of the active site. The L211F/D214E double mutant displayed an increased rate of testosterone and progesterone 6β-hydroxylation at low substrate concentrations and a decreased level of heterotropic stimulation elicited by α-naphthoflavone. Kinetic analyses of the double mutant revealed the absence of homotropic cooperativity with either steroid substrate. At low substrate concentrations the steroid 6β-hydroxylase activity of the wild-type enzyme was stimulated by a second steroid, whereas L211F/D214E displayed simple substrate inhibition. To analyze L211F/D214E at a more mechanistic level, spectral binding studies were carried out. Testosterone binding by the wild-type enzyme displayed homotropic cooperativity, whereas substrate binding by L211F/D214E displayed hyperbolic behavior.