Effect of Enamel Matrix Derivative Liquid on Osteoblast and Periodontal Ligament Cell Proliferation and Differentiation.

BACKGROUND Enamel matrix derivatives (EMDs) have been used clinically for more than a decade for the regeneration of periodontal tissues. The aim of the present study is to analyze the effect on cell growth of EMDs in a gel carrier in comparison to EMDs in a liquid carrier. EMDs in a liquid carrier have been shown to adsorb better to bone graft materials. METHODS Primary human osteoblasts and periodontal ligament (PDL) cells were exposed to EMDs in both gel and liquid carriers and compared for their ability to induce cell proliferation and differentiation. Alizarin red staining and real-time polymerase chain reaction for expression of genes encoding collagen 1, osteocalcin, and runt-related transcription factor 2, as well as bone morphogenetic protein 2 (BMP2), transforming growth factor (TGF)-β1, and interleukin (IL)-1β, were assessed. RESULTS EMDs in both carriers significantly increased cell proliferation of both osteoblasts and PDL cells in a similar manner. Both formulations also significantly upregulated the expression of genes encoding BMP2 and TGF-β1 as well as decreased the expression of IL-1β. EMDs in the liquid carrier further retained similar differentiation potential of both osteoblasts and PDL cells by demonstrating increased collagen and osteocalcin gene expression and significantly higher alizarin red staining. CONCLUSIONS The results from the present study indicate that the new formulation of EMDs in a liquid carrier is equally as potent as EMDs in a gel carrier in inducing osteoblast and PDL activity. Future study combining EMDs in a liquid carrier with bone grafting materials is required to further evaluate its potential for combination therapies.

Development of combined micro -preparation, separation, and mass spectrometry methods and application in the microdialysis study of neuropeptide metabolism

Two sets of mass spectrometry-based methods were developed specifically for the in vivo study of extracellular neuropeptide biochemistry. First, an integrated micro-concentration/desalting/matrix-addition device was constructed for matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) to achieve attomole sensitivity for microdialysis samples. Second, capillary electrophoresis (CE) was incorporated into the above micro-liquid chromatography (LC) and MALDI MS system to provide two-dimensional separation and identification (i.e. electrophoretic mobility and molecular mass) for the analysis of complex mixtures. The latter technique includes two parts of instrumentation: (1) the coupling of a preconcentration LC column to the inlet of a CE capillary, and (2) the utilization of a matrix-precoated membrane target for continuous CE effluent deposition and for automatic MALDI MS analysis (imaging) of the CE track.^ Initial in vivo data reveals a carboxypeptidase A (CPA) activity in rat brain involved in extracellular neurotensin metabolism. Benzylsuccinic acid, a CPA inhibitor, inhibited neurotensin metabolite NT1-12 formation by 70%, while inhibitors of other major extracellular peptide metabolizing enzymes increased NT1-12 formation. CPA activity has not been observed in previous in vitro experiments. Next, the validity of the methodology was demonstrated in the detection and structural elucidation of an endogenous neuropeptide, (L)VV-hemorphin-7, in rat brain upon ATP stimulation. Finally, the combined micro-LC/CE/MALDI MS was used in the in vivo metabolic study of peptide E, a mu-selective opioid peptide with 25 amino acid residues. Profiles of 88 metabolites were obtained, their identity being determined by their mass-to-charge ratio and electrophoretic mobility. The results indicate that there are several primary cleavage sites in vivo for peptide E in the release of its enkephalin-containing fragments. ^

On the Extension of the Analytic Nodal Diffusion Solver ANDES to Sodium Fast Reactors

Within the framework of the Collaborative Project for a European Sodium Fast Reactor, the reactor physics group at UPM is working on the extension of its in-house multi-scale advanced deterministic code COBAYA3 to Sodium Fast Reactors (SFR). COBAYA3 is a 3D multigroup neutron kinetics diffusion code that can be used either as a pin-by-pin code or as a stand-alone nodal code by using the analytic nodal diffusion solver ANDES. It is coupled with thermalhydraulics codes such as COBRA-TF and FLICA, allowing transient analysis of LWR at both fine-mesh and coarse-mesh scales. In order to enable also 3D pin-by-pin and nodal coupled NK-TH simulations of SFR, different developments are in progress. This paper presents the first steps towards the application of COBAYA3 to this type of reactors. ANDES solver, already extended to triangular-Z geometry, has been applied to fast reactor steady-state calculations. The required cross section libraries were generated with ERANOS code for several configurations. The limitations encountered in the application of the Analytic Coarse Mesh Finite Difference (ACMFD) method –implemented inside ANDES– to fast reactors are presented and the sensitivity of the method when using a high number of energy groups is studied. ANDES performance is assessed by comparison with the results provided by ERANOS, using a mini-core model in 33 energy groups. Furthermore, a benchmark from the NEA for a small 3D FBR in hexagonal-Z geometry and 4 energy groups is also employed to verify the behavior of the code with few energy groups.

Coupling time-stepping numerical methods and standard aerodynamics codes for instability analysis of flows in complex geometries

The development of a global instability analysis code coupling a time-stepping approach, as applied to the solution of BiGlobal and TriGlobal instability analysis 1, 2 and finite-volume-based spatial discretization, as used in standard aerodynamics codes is presented. The key advantage of the time-stepping method over matrix-formulation approaches is that the former provides a solution to the computer-storage issues associated with the latter methodology. To-date both approaches are successfully in use to analyze instability in complex geometries, although their relative advantages have never been quantified. The ultimate goal of the present work is to address this issue in the context of spatial discretization schemes typically used in industry. The time-stepping approach of Chiba 3 has been implemented in conjunction with two direct numerical simulation algorithms, one based on the typically-used in this context high-order method and another based on low-order methods representative of those in common use in industry. The two codes have been validated with solutions of the BiGlobal EVP and it has been showed that small errors in the base flow do not have affect significantly the results. As a result, a three-dimensional compressible unsteady second-order code for global linear stability has been successfully developed based on finite-volume spatial discretization and time-stepping method with the ability to study complex geometries by means of unstructured and hybrid meshes

Efficient methodologies for system matrix modelling in iterative image reconstruction for rotating high-resolution PET

A fully 3D iterative image reconstruction algorithm has been developed for high-resolution PET cameras composed of pixelated scintillator crystal arrays and rotating planar detectors, based on the ordered subsets approach. The associated system matrix is precalculated with Monte Carlo methods that incorporate physical effects not included in analytical models, such as positron range effects and interaction of the incident gammas with the scintillator material. Custom Monte Carlo methodologies have been developed and optimized for modelling of system matrices for fast iterative image reconstruction adapted to specific scanner geometries, without redundant calculations. According to the methodology proposed here, only one-eighth of the voxels within two central transaxial slices need to be modelled in detail. The rest of the system matrix elements can be obtained with the aid of axial symmetries and redundancies, as well as in-plane symmetries within transaxial slices. Sparse matrix techniques for the non-zero system matrix elements are employed, allowing for fast execution of the image reconstruction process. This 3D image reconstruction scheme has been compared in terms of image quality to a 2D fast implementation of the OSEM algorithm combined with Fourier rebinning approaches. This work confirms the superiority of fully 3D OSEM in terms of spatial resolution, contrast recovery and noise reduction as compared to conventional 2D approaches based on rebinning schemes. At the same time it demonstrates that fully 3D methodologies can be efficiently applied to the image reconstruction problem for high-resolution rotational PET cameras by applying accurate pre-calculated system models and taking advantage of the system's symmetries.

Order 10 4 speedup in global linear instability analysis using matrix formation

A unified solution framework is presented for one-, two- or three-dimensional complex non-symmetric eigenvalue problems, respectively governing linear modal instability of incompressible fluid flows in rectangular domains having two, one or no homogeneous spatial directions. The solution algorithm is based on subspace iteration in which the spatial discretization matrix is formed, stored and inverted serially. Results delivered by spectral collocation based on the Chebyshev-Gauss-Lobatto (CGL) points and a suite of high-order finite-difference methods comprising the previously employed for this type of work Dispersion-Relation-Preserving (DRP) and Padé finite-difference schemes, as well as the Summationby- parts (SBP) and the new high-order finite-difference scheme of order q (FD-q) have been compared from the point of view of accuracy and efficiency in standard validation cases of temporal local and BiGlobal linear instability. The FD-q method has been found to significantly outperform all other finite difference schemes in solving classic linear local, BiGlobal, and TriGlobal eigenvalue problems, as regards both memory and CPU time requirements. Results shown in the present study disprove the paradigm that spectral methods are superior to finite difference methods in terms of computational cost, at equal accuracy, FD-q spatial discretization delivering a speedup of ð (10 4). Consequently, accurate solutions of the three-dimensional (TriGlobal) eigenvalue problems may be solved on typical desktop computers with modest computational effort.

A Recommendation Framework Based on the Analytic Network Process and its Application in the Semantic Technology Domain

When users face a certain problem needing a product, service, or action to solve it, selecting the best alternative among them can be a dicult task due to the uncertainty of their quality. This is especially the case in the domains where users do not have an expertise, like for example in Software Engineering. Multiple criteria decision making (MCDM) methods are methods that help making better decisions when facing the complex problem of selecting the best solution among a group of alternatives that can be compared according to different conflicting criteria. In MCDM problems, alternatives represent concrete products, services or actions that will help in achieving a goal, while criteria represent the characteristics of these alternatives that are important for making a decision.

Numerical methods for option pricing.

This thesis aims to introduce some fundamental concepts underlying option valuation theory including implementation of computational tools. In many cases analytical solution for option pricing does not exist, thus the following numerical methods are used: binomial trees, Monte Carlo simulations and finite difference methods. First, an algorithm based on Hull and Wilmott is written for every method. Then these algorithms are improved in different ways. For the binomial tree both speed and memory usage is significantly improved by using only one vector instead of a whole price storing matrix. Computational time in Monte Carlo simulations is reduced by implementing a parallel algorithm (in C) which is capable of improving speed by a factor which equals the number of processors used. Furthermore, MatLab code for Monte Carlo was made faster by vectorizing simulation process. Finally, obtained option values are compared to those obtained with popular finite difference methods, and it is discussed which of the algorithms is more appropriate for which purpose.

On the Use of Matrix-Free Shift-Invert Strategies For Global Flow Instability Analysis

A novel time-stepping shift-invert algorithm for linear stability analysis of laminar flows in complex geometries is presented. This method, based on a Krylov subspace iteration, enables the solution of complex non-symmetric eigenvalue problems in a matrix-free framework. Validations and comparisons to the classical exponential method have been performed in three different cases: (i) stenotic flow, (ii) backward-facing step and (iii) lid-driven swirling flow. Results show that this new approach speeds up the required Krylov subspace iterations and has the capability of converging to specific parts of the global spectrum. It is shown that, although the exponential method remains the method of choice if leading eigenvalues are sought, the performance of the present method could be dramatically improved with the use of a preconditioner. In addition, as opposed to other methods, this strategy can be directly applied to any time-stepper, regardless of the temporal or spatial discretization of the latter.

Modelo para la integración del trazado de infraestructuras lineales en el paisaje y el medio ambiente basado en SIG

El análisis de las diferentes alternativas en la planificación y diseño de corredores y trazados de carreteras debe basarse en la correcta definición de variables territoriales que sirvan como criterios para la toma de decisión y esto requiere un análisis ambiental preliminar de esas variables de calidad. En España, los estudios de viabilidad de nuevas carreteras y autovías están asociados a una fase del proceso de decisión que se corresponde con el denominado Estudio Informativo, el cual establece condicionantes físicos, ambientales, de uso del suelo y culturales que deben ser considerados en las primeras fases de la definición del trazado de un corredor de carretera. Así, la metodología más frecuente es establecer diferentes niveles de capacidad de acogida del territorio en el área de estudio con el fin de resumir las variables territoriales en mapas temáticos y facilitar el proceso de trazado de las alternativas de corredores de carretera. El paisaje es un factor limitante a tener en cuenta en la planificación y diseño de carreteras y, por tanto, deben buscarse trazados más sostenibles en relación con criterios estéticos y ecológicos del mismo. Pero este factor no es frecuentemente analizado en los Estudios Informativos e incluso, si es considerado, los estudios específicos de la calidad del paisaje (estético y ecológico) y de las formas del terreno no incorporan las recomendaciones de las guías de trazado para evitar o reducir los impactos en el paisaje. Además, los mapas de paisaje que se generan en este tipo de estudios no se corresponden con la escala de desarrollo del Estudio Informativo (1:5.000). Otro déficit común en planificación de corredores y trazados de carreteras es que no se tiene en cuenta la conectividad del paisaje durante el proceso de diseño de la carretera para prevenir la afección a los corredores de fauna existentes en el paisaje. Este déficit puede originar un posterior efecto barrera en los movimientos dispersivos de la fauna y la fragmentación de sus hábitats debido a la ocupación parcial o total de las teselas de hábitats con importancia biológica para la fauna (o hábitats focales) y a la interrupción de los corredores de fauna que concentran esos movimientos dispersivos de la fauna entre teselas. El objetivo principal de esta tesis es mejorar el estudio del paisaje para prevenir su afección durante el proceso de trazado de carreteras, facilitar la conservación de los corredores de fauna (o pasillos verdes) y la localización de medidas preventivas y correctoras en términos de selección y cuantificación de factores de idoneidad a fin de reducir los impactos visuales y ecológicos en el paisaje a escala local. Concretamente, la incorporación de valores cuantitativos y bien justificados en el proceso de decisión permite incrementar la transparencia en el proceso de diseño de corredores y trazados de carreteras. Con este fin, se han planteado cuatro preguntas específicas en esta investigación (1) ¿Cómo se seleccionan y evalúan los factores territoriales limitantes para localizar una nueva carretera por los profesionales españoles de planificación del territorio en relación con el paisaje? (2) ¿Cómo pueden ser definidos los corredores de fauna a partir de factores del paisaje que influyen en los movimientos dispersivos de la fauna? (3) ¿Cómo pueden delimitarse y evaluarse los corredores de fauna incluyendo el comportamiento parcialmente errático en los movimientos dispersivos de la fauna y el efecto barrera de los elementos antrópicos a una escala local? (4) ¿Qué y cómo las recomendaciones de diseño de carreteras relacionadas con el paisaje y las formas del terreno pueden ser incluidas en un modelo de Sistemas de Información Geográfica (SIG) para ayudar a los ingenieros civiles durante el proceso de diseño de un trazado de carreteras bajo el punto de vista de la sostenibilidad?. Esta tesis doctoral propone nuevas metodologías que mejoran el análisis visual y ecológico del paisaje utilizando indicadores y modelos SIG para obtener alternativas de trazado que produzcan un menor impacto en el paisaje. Estas metodologías fueron probadas en un paisaje heterogéneo con una alta tasa de densidad de corzo (Capreolus capreolus L.), uno de los grandes mamíferos más atropellados en la red de carreteras españolas, y donde está planificada la construcción de una nueva autovía que atravesará la mitad del área de distribución del corzo. Inicialmente, se han analizado las variables utilizadas en 22 estudios de proyectos de planificación de corredores de carreteras promovidos por el Ministerio de Fomento entre 2006 y 2008. Estas variables se agruparon según condicionantes físicos, ambientales, de usos del suelo y culturales con el fin de comparar los valores asignados de capacidad de acogida del territorio a cada variable en los diferentes estudios revisados. Posteriormente, y como etapa previa de un análisis de conectividad, se construyó un mapa de resistencia de los movimientos dispersivos del corzo en base a la literatura y al juicio de expertos. Usando esta investigación como base, se le asignó un valor de resistencia a cada factor seleccionado para construir la matriz de resistencia, ponderándolo y combinándolo con el resto de factores usando el proceso analítico jerárquico y los operadores de lógica difusa como métodos de análisis multicriterio. Posteriormente, se diseñó una metodología SIG para delimitar claramente la extensión física de los corredores de fauna de acuerdo a un valor umbral de ancho geométrico mínimo, así como la existencia de múltiples potenciales conexiones entre cada par de teselas de hábitats presentes en el paisaje estudiado. Finalmente, se realizó un procesado de datos Light Detection and Ranging (LiDAR) y un modelo SIG para calcular la calidad del paisaje (estético y ecológico), las formas del terreno que presentan características similares para trazar una carretera y la acumulación de vistas de potenciales conductores y observadores de los alrededores de la nueva vía. Las principales contribuciones de esta investigación al conocimiento científico existente en el campo de la evaluación del impacto ambiental en relación al diseño de corredores y trazados de carreteras son cuatro. Primero, el análisis realizado de 22 Estudios Informativos de planificación de carreteras reveló que los métodos aplicados por los profesionales para la evaluación de la capacidad de acogida del territorio no fue suficientemente estandarizada, ya que había una falta de uniformidad en el uso de fuentes cartográficas y en las metodologías de evaluación de la capacidad de acogida del territorio, especialmente en el análisis de la calidad del paisaje estético y ecológico. Segundo, el análisis realizado en esta tesis destaca la importancia de los métodos multicriterio para estructurar, combinar y validar factores que limitan los movimientos dispersivos de la fauna en el análisis de conectividad. Tercero, los modelos SIG desarrollados Generador de alternativas de corredores o Generator of Alternative Corridors (GAC) y Eliminador de Corredores Estrechos o Narrow Corridor Eraser (NCE) pueden ser aplicados sistemáticamente y sobre una base científica en análisis de conectividad como una mejora de las herramientas existentes para la comprensión el paisaje como una red compuesta por nodos y enlaces interconectados. Así, ejecutando los modelos GAC y NCE de forma iterativa, pueden obtenerse corredores alternativos con similar probabilidad de ser utilizados por la fauna y sin que éstos presenten cuellos de botella. Cuarto, el caso de estudio llevado a cabo de prediseño de corredores y trazado de una nueva autovía ha sido novedoso incluyendo una clasificación semisupervisada de las formas del terreno, filtrando una nube de puntos LiDAR e incluyendo la nueva geometría 3D de la carretera en el Modelo Digital de Superficie (MDS). El uso combinado del procesamiento de datos LiDAR y de índices y clasificaciones geomorfológicas puede ayudar a los responsables encargados en la toma de decisiones a evaluar qué alternativas de trazado causan el menor impacto en el paisaje, proporciona una visión global de los juicios de valor más aplicados y, en conclusión, define qué medidas de integración paisajística correctoras deben aplicarse y dónde. ABSTRACT The assessment of different alternatives in road-corridor planning and layout design must be based on a number of well-defined territorial variables that serve as decision-making criteria, and this requires a high-quality preliminary environmental analysis of those quality variables. In Spain, feasibility studies for new roads and motorways are associated to a phase of the decision procedure which corresponds with the one known as the Informative Study, which establishes the physical, environmental, land-use and cultural constraints to be considered in the early stages of defining road corridor layouts. The most common methodology is to establish different levels of Territorial Carrying Capacity (TCC) in the study area in order to summarize the territorial variables on thematic maps and facilitate the tracing process of road-corridor layout alternatives. Landscape is a constraint factor that must be considered in road planning and design, and the most sustainable layouts should be sought based on aesthetic and ecological criteria. However this factor is not often analyzed in Informative Studies and even if it is, baseline studies on landscape quality (aesthetic and ecological) and landforms do not usually include the recommendations of road tracing guides designed to avoid or reduce impacts on the landscape. The resolution of the landscape maps produced in this type of studies does not comply with the recommended road design scale (1:5,000) in the regulations for the Informative Study procedure. Another common shortcoming in road planning is that landscape ecological connectivity is not considered during road design in order to avoid affecting wildlife corridors in the landscape. In the prior road planning stage, this issue could lead to a major barrier effect for fauna dispersal movements and to the fragmentation of their habitat due to the partial or total occupation of habitat patches of biological importance for the fauna (or focal habitats), and the interruption of wildlife corridors that concentrate fauna dispersal movements between patches. The main goal of this dissertation is to improve the study of the landscape and prevent negative effects during the road tracing process, and facilitate the preservation of wildlife corridors (or green ways) and the location of preventive and corrective measures by selecting and quantifying suitability factors to reduce visual and ecological landscape impacts at a local scale. Specifically the incorporation of quantitative and well-supported values in the decision-making process provides increased transparency in the road corridors and layouts design process. Four specific questions were raised in this research: (1) How are territorial constraints selected and evaluated in terms of landscape by Spanish land-planning practitioners before locating a new road? (2) How can wildlife corridors be defined based on the landscape factors influencing the dispersal movements of fauna? (3) How can wildlife corridors be delimited and assessed to include the partially erratic movements of fauna and the barrier effect of the anthropic elements at a local scale? (4) How recommendations of road design related to landscape and landforms can be included in a Geographic Information System (GIS) model to aid civil engineers during the road layout design process and support sustainable development? This doctoral thesis proposes new methodologies that improve the assessment of the visual and ecological landscape character using indicators and GIS models to obtain road layout alternatives with a lower impact on the landscape. These methodologies were tested on a case study of a heterogeneous landscape with a high density of roe deer (Capreolus capreolus L.) –one of the large mammals most commonly hit by vehicles on the Spanish road network– and where a new motorway is planned to pass through the middle of their distribution area. We explored the variables used in 22 road-corridor planning projects sponsored by the Ministry of Public Works between 2006 and 2008. These variables were grouped into physical, environmental, land-use and cultural constraints for the purpose of comparing the TCC values assigned to each variable in the various studies reviewed. As a prior stage in a connectivity analysis, a map of resistance to roe deer dispersal movements was created based on the literature and experts judgment. Using this research as a base, each factor selected to build the matrix was assigned a resistance value and weighted and combined with the rest of the factors using the analytic hierarchy process (AHP) and fuzzy logic operators as multicriteria assessment (MCA) methods. A GIS methodology was designed to clearly delimit the physical area of wildlife corridors according to a geometric threshold width value, and the multiple potential connections between each pair of habitat patches in the landscape. A Digital Surface Model Light Detection and Ranging (LiDAR) dataset processing and a GIS model was performed to determine landscape quality (aesthetic and ecological) and landforms with similar characteristics for the road layout, and the cumulative viewshed of potential drivers and observers in the area surrounding the new motorway. The main contributions of this research to current scientific knowledge in the field of environmental impact assessment for road corridors and layouts design are four. First, the analysis of 22 Informative Studies on road planning revealed that the methods applied by practitioners for assessing the TCC were not sufficiently standardized due to the lack of uniformity in the cartographic information sources and the TCC valuation methodologies, especially in the analysis of the aesthetic and ecological quality of the landscape. Second, the analysis in this dissertation highlights the importance of multicriteria methods to structure, combine and validate factors that constrain wildlife dispersal movements in the connectivity analysis. Third, the “Generator of Alternative Corridors (GAC)” and “Narrow Corridor Eraser (NCE)” GIS models developed can be applied systematically and on a scientific basis in connectivity analyses to improve existing tools and understand landscape as a network composed of interconnected nodes and links. Thus, alternative corridors with similar probability of use by fauna and without bottlenecks can be obtained by iteratively running GAC and NCE models. Fourth, our case study of new motorway corridors and layouts design innovatively included semi-supervised classification of landforms, filtering of LiDAR point clouds and new 3D road geometry on the Digital Surface Model (DSM). The combined used of LiDAR data processing and geomorphological indices and classifications can help decision-makers assess which road layouts produce lower impacts on the landscape, provide an overall insight into the most commonly applied value judgments, and in conclusion, define which corrective measures should be applied in terms of landscaping, and where.

Dominance measuring methods within MAVT/MAUT with imprecise information concerning decision-makers'preferences

Dominance measuring methods are an approach for dealing with complex decision-making problems with imprecise information within multi-attribute value/utility theory. These methods are based on the computation of pairwise dominance values and exploit the information in the dominance matrix in different ways to derive measures of dominance intensity and rank the alternatives under consideration. In this paper we review dominance measuring methods proposed in the literature for dealing with imprecise information (intervals, ordinal information or fuzzy numbers) about decision-makers? preferences and their performance in comparison with other existing approaches, like SMAA and SMAA-II or Sarabando and Dias? method.

New methods for the synthesis of radiation patterns of coupled antenna arrays = Nuevos métodos de síntesis de diagramas de radiación de agrupaciones de antenas acopladas

El principal objetivo de esta tesis es el desarrollo de métodos de síntesis de diagramas de radiación de agrupaciones de antenas, en donde se realiza una caracterización electromagnética rigurosa de los elementos radiantes y de los acoplos mutuos existentes. Esta caracterización no se realiza habitualmente en la gran mayoría de métodos de síntesis encontrados en la literatura, debido fundamentalmente a dos razones. Por un lado, se considera que el diagrama de radiación de un array de antenas se puede aproximar con el factor de array que únicamente tiene en cuenta la posición de los elementos y las excitaciones aplicadas a los mismos. Sin embargo, como se mostrará en esta tesis, en múltiples ocasiones un riguroso análisis de los elementos radiantes y del acoplo mutuo entre ellos es importante ya que los resultados obtenidos pueden ser notablemente diferentes. Por otro lado, no es sencillo combinar un método de análisis electromagnético con un proceso de síntesis de diagramas de radiación. Los métodos de análisis de agrupaciones de antenas suelen ser costosos computacionalmente, ya que son estructuras grandes en términos de longitudes de onda. Generalmente, un diseño de un problema electromagnético suele comprender varios análisis de la estructura, dependiendo de las variaciones de las características, lo que hace este proceso muy costoso. Dos métodos se utilizan en esta tesis para el análisis de los arrays acoplados. Ambos están basados en el método de los elementos finitos, la descomposición de dominio y el análisis modal para analizar la estructura radiante y han sido desarrollados en el grupo de investigación donde se engloba esta tesis. El primero de ellos es una técnica de análisis de arrays finitos basado en la aproximación de array infinito. Su uso es indicado para arrays planos de grandes dimensiones con elementos equiespaciados. El segundo caracteriza el array y el acoplo mutuo entre elementos a partir de una expansión en modos esféricos del campo radiado por cada uno de los elementos. Este método calcula los acoplos entre los diferentes elementos del array usando las propiedades de traslación y rotación de los modos esféricos. Es capaz de analizar agrupaciones de elementos distribuidos de forma arbitraria. Ambas técnicas utilizan una formulación matricial que caracteriza de forma rigurosa el campo radiado por el array. Esto las hace muy apropiadas para su posterior uso en una herramienta de diseño, como los métodos de síntesis desarrollados en esta tesis. Los resultados obtenidos por estas técnicas de síntesis, que incluyen métodos rigurosos de análisis, son consecuentemente más precisos. La síntesis de arrays consiste en modificar uno o varios parámetros de las agrupaciones de antenas buscando unas determinadas especificaciones de las características de radiación. Los parámetros utilizados como variables de optimización pueden ser varios. Los más utilizados son las excitaciones aplicadas a los elementos, pero también es posible modificar otros parámetros de diseño como son las posiciones de los elementos o las rotaciones de estos. Los objetivos de las síntesis pueden ser dirigir el haz o haces en una determinada dirección o conformar el haz con formas arbitrarias. Además, es posible minimizar el nivel de los lóbulos secundarios o del rizado en las regiones deseadas, imponer nulos que evitan posibles interferencias o reducir el nivel de la componente contrapolar. El método para el análisis de arrays finitos basado en la aproximación de array infinito considera un array finito como un array infinito con un número finito de elementos excitados. Los elementos no excitados están físicamente presentes y pueden presentar tres diferentes terminaciones, corto-circuito, circuito abierto y adaptados. Cada una de estas terminaciones simulará mejor el entorno real en el que el array se encuentre. Este método de análisis se integra en la tesis con dos métodos diferentes de síntesis de diagramas de radiación. En el primero de ellos se presenta un método basado en programación lineal en donde es posible dirigir el haz o haces, en la dirección deseada, además de ejercer un control sobre los lóbulos secundarios o imponer nulos. Este método es muy eficiente y obtiene soluciones óptimas. El mismo método de análisis es también aplicado a un método de conformación de haz, en donde un problema originalmente no convexo (y de difícil solución) es transformado en un problema convexo imponiendo restricciones de simetría, resolviendo de este modo eficientemente un problema complejo. Con este método es posible diseñar diagramas de radiación con haces de forma arbitraria, ejerciendo un control en el rizado del lóbulo principal, así como en el nivel de los lóbulos secundarios. El método de análisis de arrays basado en la expansión en modos esféricos se integra en la tesis con tres técnicas de síntesis de diagramas de radiación. Se propone inicialmente una síntesis de conformación del haz basado en el método de la recuperación de fase resuelta de forma iterativa mediante métodos convexos, en donde relajando las restricciones del problema original se consiguen unas soluciones cercanas a las óptimas de manera eficiente. Dos métodos de síntesis se han propuesto, donde las variables de optimización son las posiciones y las rotaciones de los elementos respectivamente. Se define una función de coste basada en la intensidad de radiación, la cual es minimizada de forma iterativa con el método del gradiente. Ambos métodos reducen el nivel de los lóbulos secundarios minimizando una función de coste. El gradiente de la función de coste es obtenido en términos de la variable de optimización en cada método. Esta función de coste está formada por la expresión rigurosa de la intensidad de radiación y por una función de peso definida por el usuario para imponer prioridades sobre las diferentes regiones de radiación, si así se desea. Por último, se presenta un método en el cual, mediante técnicas de programación entera, se buscan las fases discretas que generan un diagrama de radiación lo más cercano posible al deseado. Con este método se obtienen diseños que minimizan el coste de fabricación. En cada uno de las diferentes técnicas propuestas en la tesis, se presentan resultados con elementos reales que muestran las capacidades y posibilidades que los métodos ofrecen. Se comparan los resultados con otros métodos disponibles en la literatura. Se muestra la importancia de tener en cuenta los diagramas de los elementos reales y los acoplos mutuos en el proceso de síntesis y se comparan los resultados obtenidos con herramientas de software comerciales. ABSTRACT The main objective of this thesis is the development of optimization methods for the radiation pattern synthesis of array antennas in which a rigorous electromagnetic characterization of the radiators and the mutual coupling between them is performed. The electromagnetic characterization is usually overlooked in most of the available synthesis methods in the literature, this is mainly due to two reasons. On the one hand, it is argued that the radiation pattern of an array is mainly influenced by the array factor and that the mutual coupling plays a minor role. As it is shown in this thesis, the mutual coupling and the rigorous characterization of the array antenna influences significantly in the array performance and its computation leads to differences in the results obtained. On the other hand, it is difficult to introduce an analysis procedure into a synthesis technique. The analysis of array antennas is generally expensive computationally as the structure to analyze is large in terms of wavelengths. A synthesis method requires to carry out a large number of analysis, this makes the synthesis problem very expensive computationally or intractable in some cases. Two methods have been used in this thesis for the analysis of coupled antenna arrays, both of them have been developed in the research group in which this thesis is involved. They are based on the finite element method (FEM), the domain decomposition and the modal analysis. The first one obtains a finite array characterization with the results obtained from the infinite array approach. It is specially indicated for the analysis of large arrays with equispaced elements. The second one characterizes the array elements and the mutual coupling between them with a spherical wave expansion of the radiated field by each element. The mutual coupling is computed using the properties of translation and rotation of spherical waves. This method is able to analyze arrays with elements placed on an arbitrary distribution. Both techniques provide a matrix formulation that makes them very suitable for being integrated in synthesis techniques, the results obtained from these synthesis methods will be very accurate. The array synthesis stands for the modification of one or several array parameters looking for some desired specifications of the radiation pattern. The array parameters used as optimization variables are usually the excitation weights applied to the array elements, but some other array characteristics can be used as well, such as the array elements positions or rotations. The desired specifications may be to steer the beam towards any specific direction or to generate shaped beams with arbitrary geometry. Further characteristics can be handled as well, such as minimize the side lobe level in some other radiating regions, to minimize the ripple of the shaped beam, to take control over the cross-polar component or to impose nulls on the radiation pattern to avoid possible interferences from specific directions. The analysis method based on the infinite array approach considers an infinite array with a finite number of excited elements. The infinite non-excited elements are physically present and may have three different terminations, short-circuit, open circuit and match terminated. Each of this terminations is a better simulation for the real environment of the array. This method is used in this thesis for the development of two synthesis methods. In the first one, a multi-objective radiation pattern synthesis is presented, in which it is possible to steer the beam or beams in desired directions, minimizing the side lobe level and with the possibility of imposing nulls in the radiation pattern. This method is very efficient and obtains optimal solutions as it is based on convex programming. The same analysis method is used in a shaped beam technique in which an originally non-convex problem is transformed into a convex one applying symmetry restrictions, thus solving a complex problem in an efficient way. This method allows the synthesis of shaped beam radiation patterns controlling the ripple in the mainlobe and the side lobe level. The analysis method based on the spherical wave expansion is applied for different synthesis techniques of the radiation pattern of coupled arrays. A shaped beam synthesis is presented, in which a convex formulation is proposed based on the phase retrieval method. In this technique, an originally non-convex problem is solved using a relaxation and solving a convex problems iteratively. Two methods are proposed based on the gradient method. A cost function is defined involving the radiation intensity of the coupled array and a weighting function that provides more degrees of freedom to the designer. The gradient of the cost function is computed with respect to the positions in one of them and the rotations of the elements in the second one. The elements are moved or rotated iteratively following the results of the gradient. A highly non-convex problem is solved very efficiently, obtaining very good results that are dependent on the starting point. Finally, an optimization method is presented where discrete digital phases are synthesized providing a radiation pattern as close as possible to the desired one. The problem is solved using linear integer programming procedures obtaining array designs that greatly reduce the fabrication costs. Results are provided for every method showing the capabilities that the above mentioned methods offer. The results obtained are compared with available methods in the literature. The importance of introducing a rigorous analysis into the synthesis method is emphasized and the results obtained are compared with a commercial software, showing good agreement.

A technique for detecting matrix proteins in the crystalline spicule of the sea urchin embryo.

The presence of proteins associated with the CaCO3-containing biocrystals found in a wide variety of marine organisms is well established. In these organisms, including the primitive skeleton (spicule) of the sea urchin embryo, the structural and functional role of these proteins either in the biomineralization process or in control of the structural features of the biocrystals is unclear. Recently, one of the matrix proteins of the sea urchin spicule, SM 30, has been shown to contain a carbohydrate chain (the 1223 epitope) that has been implicated in the process whereby Ca2+ is deposited as CaCo3. Because an understanding of the localization of this protein, as well as other proteins found within the spicule, is central to understanding their function, we undertook to develop methods to localize spicule matrix proteins in intact spicules, using immunogold techniques and scanning electron microscopy. Gold particles indicative of this matrix glycoprotein could not be detected on the surface of spicules that had been isolated from embryo homogenates and treated with alkaline hypochlorite to remove any associated membranous material. However, when isolated spicules were etched for 2 min with dilute acetic acid (10 mM) to expose more internal regions of the crystal, SM 30 and perhaps other proteins bearing the 1223 carbohydrate epitope were detected in the calcite matrix. These results, indicating that these two antigens are widely distributed in the spicule, suggest that this technique should be applicable to any matrix protein for which antibodies are available.

Determination of absorption curves, dissolution profiles and establishment of in vitro-in vivo correlation by in silico methods using GastroPlusTM and DDDPlusTM

The use of computer programs to predict drug absorption in humans and to simulate dissolution profiles has become a valuable tool in the pharmaceutical area. The objective of this study was to use in silico methods through software GastroPlusTM and DDDPlusTM to simulate drug absorption curves and dissolution profiles, and to establish in vitro-in vivo correlations (IVIVCs). The work presented herein is divided into five chapters and includes the drugs ketoprofen, pyrimethamine, metronidazole, fluconazole, carvedilol and doxazosin. In Chapter 1, simulated plasma curves for ketoprofen matrix tablets are presented and IVIVC was established. The use of simulated intrinsic dissolution tests for pyrimethamine and metronidazole as a tool for biopharmaceutics classification is detailed in Chapter 2. In Chapter 3, simulation of plasma curves for fluconazole capsules with different dissolution profiles is demonstrated as a tool for biowaiver. IVIVC studies were also conducted for carvedilol immediate-release tablets from dissolution profiles in Chapter 4. Chapter 5 covers the application of simulated dissolution tests for development of doxazosin extended-release formulations. Simulation of plasma curves and IVIVC using the software GastroPlusTM as well as intrinsic dissolution tests and dissolution profiles using the software DDDPlusTM proved to be a tool of wide application in predicting biopharmaceutical characteristics of drugs and formulations, allowing the reduction of time and costs of experimental laboratory work.

A Meta-Analytic Review of Mindfulness-Based Interventions on Symptom Reduction: A Critique and Guide for Future Investigation.

Over the past decade, mindfulness practices have been used with increasing frequency as therapeutic components within cognitive behavioral treatment regimens. As is standard practice, prescriptive uses of mindfulness intervention are incorporated to improve end-state functioning by ameliorating problematic symptoms and conditions. Common change-targets include the control of cognitive and emotional content for purposes of enhancing psychological self-regulation and physical well-being. The term mindfulness applies to a heterogeneous range of practices, methods, and techniques. While there is no singular agreed upon definition for mindfulness, as a process concept, the term connotes an immediate, non-thetic access to events, wherein each occasioning event is experienced in toto within the broader contextual event-field, and distinct from intervening conceptual themes being noticed. Training in mindfulness practices may be conducted using individual, group, or small class formats. The current paper provides a meta-analytic review of 44 treatment outcome studies (extracted 1982 through 2006), which examines the clinical utility of mindfulness as the primary therapeutic approach. Results indicated that average effect sizes for mindfulness based interventions fell within the medium range for construct category variables examined (d = .56). These findings suggest that mindfulness training is a cost-effective treatment for a wide array of contemporary psychological problems and diagnoses, in addition to fostering positive psychology attributes such as quality and satisfaction with life. A critique of the research and recommendations for future research, including a need to examine the role of mindfulness as a tool for cultivating increased psychological acceptance and life satisfaction, is presented.