Nanoinformatics: a new area of research in nanomedicine

Over a decade ago, nanotechnologists began research on applications of nanomaterials for medicine. This research has revealed a wide range of different challenges, as well as many opportunities. Some of these challenges are strongly related to informatics issues, dealing, for instance, with the management and integration of heterogeneous information, defining nomenclatures, taxonomies and classifications for various types of nanomaterials, and research on new modeling and simulation techniques for nanoparticles. Nanoinformatics has recently emerged in the USA and Europe to address these issues. In this paper, we present a review of nanoinformatics, describing its origins, the problems it addresses, areas of interest, and examples of current research initiatives and informatics resources. We suggest that nanoinformatics could accelerate research and development in nanomedicine, as has occurred in the past in other fields. For instance, biomedical informatics served as a fundamental catalyst for the Human Genome Project, and other genomic and ?omics projects, as well as the translational efforts that link resulting molecular-level research to clinical problems and findings.

Dominance intensity measure within fuzzy weight oriented MAUT: an application

We introduce a dominance intensity measuring method to derive a ranking of alternatives to deal with incomplete information in multi-criteria decision-making problems on the basis of multi-attribute utility theory (MAUT) and fuzzy sets theory. We consider the situation where there is imprecision concerning decision-makers’ preferences, and imprecise weights are represented by trapezoidal fuzzy weights.The proposed method is based on the dominance values between pairs of alternatives. These values can be computed by linear programming, as an additive multi-attribute utility model is used to rate the alternatives. Dominance values are then transformed into dominance intensity measures, used to rank the alternatives under consideration. Distances between fuzzy numbers based on the generalization of the left and right fuzzy numbers are utilized to account for fuzzy weights. An example concerning the selection of intervention strategies to restore an aquatic ecosystem contaminated by radionuclides illustrates the approach. Monte Carlo simulation techniques have been used to show that the proposed method performs well for different imprecision levels in terms of a hit ratio and a rank-order correlation measure.

A new dominance intensity method to deal with ordinal information about a DM's preferences within MAVT

Dominance measuring methods are a new approach to deal with complex decision-making problems with imprecise information. These methods are based on the computation of pairwise dominance values and exploit the information in the dominance matrix in dirent ways to derive measures of dominance intensity and rank the alternatives under consideration. In this paper we propose a new dominance measuring method to deal with ordinal information about decision-maker preferences in both weights and component utilities. It takes advantage of the centroid of the polytope delimited by ordinal information and builds triangular fuzzy numbers whose distances to the crisp value 0 constitute the basis for the de?nition of a dominance intensity measure. Monte Carlo simulation techniques have been used to compare the performance of this method with other existing approaches.

Microstructure-based numerical modeling of the mechanical behavior of Mg alloys

Dentro de los materiales estructurales, el magnesio y sus aleaciones están siendo el foco de una de profunda investigación. Esta investigación está dirigida a comprender la relación existente entre la microestructura de las aleaciones de Mg y su comportamiento mecánico. El objetivo es optimizar las aleaciones actuales de magnesio a partir de su microestructura y diseñar nuevas aleaciones. Sin embargo, el efecto de los factores microestructurales (como la forma, el tamaño, la orientación de los precipitados y la morfología de los granos) en el comportamiento mecánico de estas aleaciones está todavía por descubrir. Para conocer mejor de la relación entre la microestructura y el comportamiento mecánico, es necesaria la combinación de técnicas avanzadas de caracterización experimental como de simulación numérica, a diferentes longitudes de escala. En lo que respecta a las técnicas de simulación numérica, la homogeneización policristalina es una herramienta muy útil para predecir la respuesta macroscópica a partir de la microestructura de un policristal (caracterizada por el tamaño, la forma y la distribución de orientaciones de los granos) y el comportamiento del monocristal. La descripción de la microestructura se lleva a cabo mediante modernas técnicas de caracterización (difracción de rayos X, difracción de electrones retrodispersados, así como con microscopia óptica y electrónica). Sin embargo, el comportamiento del cristal sigue siendo difícil de medir, especialmente en aleaciones de Mg, donde es muy complicado conocer el valor de los parámetros que controlan el comportamiento mecánico de los diferentes modos de deslizamiento y maclado. En la presente tesis se ha desarrollado una estrategia de homogeneización computacional para predecir el comportamiento de aleaciones de magnesio. El comportamiento de los policristales ha sido obtenido mediante la simulación por elementos finitos de un volumen representativo (RVE) de la microestructura, considerando la distribución real de formas y orientaciones de los granos. El comportamiento del cristal se ha simulado mediante un modelo de plasticidad cristalina que tiene en cuenta los diferentes mecanismos físicos de deformación, como el deslizamiento y el maclado. Finalmente, la obtención de los parámetros que controlan el comportamiento del cristal (tensiones críticas resueltas (CRSS) así como las tasas de endurecimiento para todos los modos de maclado y deslizamiento) se ha resuelto mediante la implementación de una metodología de optimización inversa, una de las principales aportaciones originales de este trabajo. La metodología inversa pretende, por medio del algoritmo de optimización de Levenberg-Marquardt, obtener el conjunto de parámetros que definen el comportamiento del monocristal y que mejor ajustan a un conjunto de ensayos macroscópicos independientes. Además de la implementación de la técnica, se han estudiado tanto la objetividad del metodología como la unicidad de la solución en función de la información experimental. La estrategia de optimización inversa se usó inicialmente para obtener el comportamiento cristalino de la aleación AZ31 de Mg, obtenida por laminado. Esta aleación tiene una marcada textura basal y una gran anisotropía plástica. El comportamiento de cada grano incluyó cuatro mecanismos de deformación diferentes: deslizamiento en los planos basal, prismático, piramidal hc+ai, junto con el maclado en tracción. La validez de los parámetros resultantes se validó mediante la capacidad del modelo policristalino para predecir ensayos macroscópicos independientes en diferentes direcciones. En segundo lugar se estudió mediante la misma estrategia, la influencia del contenido de Neodimio (Nd) en las propiedades de una aleación de Mg-Mn-Nd, obtenida por extrusión. Se encontró que la adición de Nd produce una progresiva isotropización del comportamiento macroscópico. El modelo mostró que este incremento de la isotropía macroscópica era debido tanto a la aleatoriedad de la textura inicial como al incremento de la isotropía del comportamiento del cristal, con valores similares de las CRSSs de los diferentes modos de deformación. Finalmente, el modelo se empleó para analizar el efecto de la temperatura en el comportamiento del cristal de la aleación de Mg-Mn-Nd. La introducción en el modelo de los efectos non-Schmid sobre el modo de deslizamiento piramidal hc+ai permitió capturar el comportamiento mecánico a temperaturas superiores a 150_C. Esta es la primera vez, de acuerdo con el conocimiento del autor, que los efectos non-Schmid han sido observados en una aleación de Magnesio. The study of Magnesium and its alloys is a hot research topic in structural materials. In particular, special attention is being paid in understanding the relationship between microstructure and mechanical behavior in order to optimize the current alloy microstructures and guide the design of new alloys. However, the particular effect of several microstructural factors (precipitate shape, size and orientation, grain morphology distribution, etc.) in the mechanical performance of a Mg alloy is still under study. The combination of advanced characterization techniques and modeling at several length scales is necessary to improve the understanding of the relation microstructure and mechanical behavior. Respect to the simulation techniques, polycrystalline homogenization is a very useful tool to predict the macroscopic response from polycrystalline microstructure (grain size, shape and orientation distributions) and crystal behavior. The microstructure description is fully covered with modern characterization techniques (X-ray diffraction, EBSD, optical and electronic microscopy). However, the mechanical behaviour of single crystals is not well-known, especially in Mg alloys where the correct parameterization of the mechanical behavior of the different slip/twin modes is a very difficult task. A computational homogenization framework for predicting the behavior of Magnesium alloys has been developed in this thesis. The polycrystalline behavior was obtained by means of the finite element simulation of a representative volume element (RVE) of the microstructure including the actual grain shape and orientation distributions. The crystal behavior for the grains was accounted for a crystal plasticity model which took into account the physical deformation mechanisms, e.g. slip and twinning. Finally, the problem of the parametrization of the crystal behavior (critical resolved shear stresses (CRSS) and strain hardening rates of all the slip and twinning modes) was obtained by the development of an inverse optimization methodology, one of the main original contributions of this thesis. The inverse methodology aims at finding, by means of the Levenberg-Marquardt optimization algorithm, the set of parameters defining crystal behavior that best fit a set of independent macroscopic tests. The objectivity of the method and the uniqueness of solution as function of the input information has been numerically studied. The inverse optimization strategy was first used to obtain the crystal behavior of a rolled polycrystalline AZ31 Mg alloy that showed a marked basal texture and a strong plastic anisotropy. Four different deformation mechanisms: basal, prismatic and pyramidal hc+ai slip, together with tensile twinning were included to characterize the single crystal behavior. The validity of the resulting parameters was proved by the ability of the polycrystalline model to predict independent macroscopic tests on different directions. Secondly, the influence of Neodymium (Nd) content on an extruded polycrystalline Mg-Mn-Nd alloy was studied using the same homogenization and optimization framework. The effect of Nd addition was a progressive isotropization of the macroscopic behavior. The model showed that this increase in the macroscopic isotropy was due to a randomization of the initial texture and also to an increase of the crystal behavior isotropy (similar values of the CRSSs of the different modes). Finally, the model was used to analyze the effect of temperature on the crystal behaviour of a Mg-Mn-Nd alloy. The introduction in the model of non-Schmid effects on the pyramidal hc+ai slip allowed to capture the inverse strength differential that appeared, between the tension and compression, above 150_C. This is the first time, to the author's knowledge, that non-Schmid effects have been reported for Mg alloys.

Analysis of Combined Bending and Punching Tests of Reinforced Concrete Slabs within IMPACT III Project

The paper reports on a collaborative effort between the Swiss Federal Nuclear Safety Inspectorate (ENSI) and their consultants Principia and Stangenberg. As part of the IMPACT III project, reduced scale impact tests of reinforced concrete structures were carried out. The simulation of test X3 is presented here and the numerical results are compared with those obtained in the test, carried out in August 2013. The general object is to improve the safety of nuclear facilities and, more specifically, to demonstrate the capabilities of current simulation techniques to reproduce the behaviour of a reinforced concrete structure impacted by a soft missile. The missile is a steel tube with a mass of 50 kg and travelling at 140 m/s. The target is a 250 mm thick, 2,1 m by 2,1 m reinforced concrete wall, held in a stiff supporting frame. The reinforcement includes both longitudinal and transverse rebars. Calculations were carried out before and after the test with Abaqus (Principia) and SOFiSTiK (Stangenberg). In the Abaqus simulation the concrete is modelled using solid elements and a damaged plasticity formulation, the rebars with embedded beam elements, and the missile with shell elements. In SOFiSTiK the target is modelled with non-linear, layered shell elements for the reinforcement on both sides; non-linear shear deformations of shell/plate elements are approximately included. The results generally indicate a good agreement between calculations and measurements.

Análisis, desarrollo y optimización de un sistema para el diseño de redes topográficas valorando el modelo digital del terreno

El presente trabajo tiene como objetivo general el análisis de las técnicas de diseño y optimización de redes topográficas, observadas mediante topografía convencional (no satelital) el desarrollo e implementación de un sistema informático capaz de ayudar a la definición de la geometría más fiable y precisa, en función de la orografía del terreno donde se tenga que ubicar. En primer lugar se realizará un estudio de la metodología del ajuste mediante mínimos cuadrados y la propagación de varianzas, para posteriormente analizar su dependencia de la geometría que adopte la red. Será imprescindible determinar la independencia de la matriz de redundancia (R) de las observaciones y su total dependencia de la geometría, así como la influencia de su diagonal principal (rii), números de redundancia, para garantizar la máxima fiabilidad interna de la misma. También se analizará el comportamiento de los números de redundancia (rii) en el diseño de una red topográfica, la variación de dichos valores en función de la geometría, analizando su independencia respecto de las observaciones así como los diferentes niveles de diseño en función de los parámetros y datos conocidos. Ha de señalarse que la optimización de la red, con arreglo a los criterios expuestos, está sujeta a los condicionantes que impone la necesidad de que los vértices sean accesibles, y además sean visibles entre sí, aquellos relacionados por observaciones, situaciones que dependen esencialmente del relieve del terreno y de los obstáculos naturales o artificiales que puedan existir. Esto implica la necesidad de incluir en el análisis y en el diseño, cuando menos de un modelo digital del terreno (MDT), aunque lo más útil sería la inclusión en el estudio del modelo digital de superficie (MDS), pero esta opción no siempre será posible. Aunque el tratamiento del diseño esté basado en un sistema bidimensional se estudiará la posibilidad de incorporar un modelo digital de superficie (MDS); esto permitirá a la hora de diseñar el emplazamiento de los vértices de la red la viabilidad de las observaciones en función de la orografía y los elementos, tanto naturales como artificiales, que sobre ella estén ubicados. Este sistema proporcionaría, en un principio, un diseño óptimo de una red constreñida, atendiendo a la fiabilidad interna y a la precisión final de sus vértices, teniendo en cuenta la orografía, lo que equivaldría a resolver un planteamiento de diseño en dos dimensiones y media1; siempre y cuando se dispusiera de un modelo digital de superficie o del terreno. Dado que la disponibilidad de obtener de manera libre el MDS de las zonas de interés del proyecto, hoy en día es costoso2, se planteará la posibilidad de conjuntar, para el estudio del diseño de la red, de un modelo digital del terreno. Las actividades a desarrollar en el trabajo de esta tesis se describen en esta memoria y se enmarcan dentro de la investigación para la que se plantean los siguientes objetivos globales: 1. Establecer un modelo matemático del proceso de observación de una red topográfica, atendiendo a todos los factores que intervienen en el mismo y a su influencia sobre las estimaciones de las incógnitas que se obtienen como resultado del ajuste de las observaciones. 2. Desarrollar un sistema que permita optimizar una red topográfica en sus resultados, aplicando técnicas de diseño y simulación sobre el modelo anterior. 3. Presentar una formulación explícita y rigurosa de los parámetros que valoran la fiabilidad de una red topográfica y de sus relaciones con el diseño de la misma. El logro de este objetivo se basa, además de en la búsqueda y revisión de las fuentes, en una intensa labor de unificación de notaciones y de construcción de pasos intermedios en los desarrollos matemáticos. 4. Elaborar una visión conjunta de la influencia del diseño de una red, en los seis siguientes factores (precisiones a posteriori, fiabilidad de las observaciones, naturaleza y viabilidad de las mismas, instrumental y metodología de estacionamiento) como criterios de optimización, con la finalidad de enmarcar el tema concreto que aquí se aborda. 5. Elaborar y programar los algoritmos necesarios para poder desarrollar una aplicación que sea capaz de contemplar las variables planteadas en el apartado anterior en el problema del diseño y simulación de redes topográficas, contemplando el modelo digital de superficie. Podrían considerarse como objetivos secundarios, los siguientes apartados: Desarrollar los algoritmos necesarios para interrelacionar el modelo digital del terreno con los propios del diseño. Implementar en la aplicación informática la posibilidad de variación, por parte del usuario, de los criterios de cobertura de los parámetros (distribución normal o t de Student), así como los grados de fiabilidad de los mismos ABSTRACT The overall purpose of this work is the analysis of the techniques of design and optimization for geodetic networks, measured with conventional survey methods (not satellite), the development and implementation of a computational system capable to help on the definition of the most liable and accurate geometry, depending on the land orography where the network has to be located. First of all, a study of the methodology by least squares adjustment and propagation of variances will be held; then, subsequently, analyze its dependency of the geometry that the network will take. It will be essential to determine the independency of redundancy matrix (R) from the observations and its absolute dependency from the network geometry, as well as the influence of the diagonal terms of the R matrix (rii), redundancy numbers, in order to ensure maximum re liability of the network. It will also be analyzed first the behavior of redundancy numbers (rii) in surveying network design, then the variation of these values depending on the geometry with the analysis of its independency from the observations, and finally the different design levels depending on parameters and known data. It should be stated that network optimization, according to exposed criteria, is subject to the accessibility of the network points. In addition, common visibility among network points, which of them are connected with observations, has to be considered. All these situations depends essentially on the terrain relief and the natural or artificial obstacles that should exist. Therefore, it is necessary to include, at least, a digital terrain model (DTM), and better a digital surface model (DSM), not always available. Although design treatment is based on a bidimensional system, the possibility of incorporating a digital surface model (DSM) will be studied; this will allow evaluating the observations feasibility based on the terrain and the elements, both natural and artificial, which are located on it, when selecting network point locations. This system would provide, at first, an optimal design of a constrained network, considering both the internal reliability and the accuracy of its points (including the relief). This approach would amount to solving a “two and a half dimensional”3 design, if a digital surface model is available. As the availability of free DSM4 of the areas of interest of the project today is expensive, the possibility of combining a digital terrain model will arise. The activities to be developed on this PhD thesis are described in this document and are part of the research for which the following overall objectives are posed: 1. To establish a mathematical model for the process of observation of a survey network, considering all the factors involved and its influence on the estimates of the unknowns that are obtained as a result of the observations adjustment. 2. To develop a system to optimize a survey network results, applying design and simulation techniques on the previous model. 3. To present an explicit and rigorous formulation of parameters which assess the reliability of a survey network and its relations with the design. The achievement of this objective is based, besides on the search and review of sources, in an intense work of unification of notation and construction of intermediate steps in the mathematical developments. 4. To develop an overview of the influence on the network design of six major factors (posterior accuracy, observations reliability, viability of observations, instruments and station methodology) as optimization criteria, in order to define the subject approached on this document. 5. To elaborate and program the algorithms needed to develop an application software capable of considering the variables proposed in the previous section, on the problem of design and simulation of surveying networks, considering the digital surface model. It could be considered as secondary objectives, the following paragraphs: To develop the necessary algorithms to interrelate the digital terrain model with the design ones. To implement in the software application the possibility of variation of the coverage criteria parameters (normal distribution or Student t test) and therefore its degree of reliability.

Atomistic modeling of Ge damage accumulation, amorphization and solid phase epitaxial regrowth

En los últimos años, el Ge ha ganado de nuevo atención con la finalidad de ser integrado en el seno de las existentes tecnologías de microelectrónica. Aunque no se le considera como un canddato capaz de reemplazar completamente al Si en el futuro próximo, probalemente servirá como un excelente complemento para aumentar las propiedades eléctricas en dispositivos futuros, especialmente debido a su alta movilidad de portadores. Esta integración requiere de un avance significativo del estado del arte en los procesos de fabricado. Técnicas de simulación, como los algoritmos de Monte Carlo cinético (KMC), proporcionan un ambiente atractivo para llevar a cabo investigación y desarrollo en este campo, especialmente en términos de costes en tiempo y financiación. En este estudio se han usado, por primera vez, técnicas de KMC con el fin entender el procesado “front-end” de Ge en su fabricación, específicamente la acumulación de dañado y amorfización producidas por implantación iónica y el crecimiento epitaxial en fase sólida (SPER) de las capas amorfizadas. Primero, simulaciones de aproximación de clisiones binarias (BCA) son usadas para calcular el dañado causado por cada ión. La evolución de este dañado en el tiempo se simula usando KMC sin red, o de objetos (OKMC) en el que sólamente se consideran los defectos. El SPER se simula a través de una aproximación KMC de red (LKMC), siendo capaz de seguir la evolución de los átomos de la red que forman la intercara amorfo/cristalina. Con el modelo de amorfización desarrollado a lo largo de este trabajo, implementado en un simulador multi-material, se pueden simular todos estos procesos. Ha sido posible entender la acumulación de dañado, desde la generación de defectos puntuales hasta la formación completa de capas amorfas. Esta acumulación ocurre en tres regímenes bien diferenciados, empezando con un ritmo lento de formación de regiones de dañado, seguido por una rápida relajación local de ciertas áreas en la fase amorfa donde ambas fases, amorfa y cristalina, coexisten, para terminar en la amorfización completa de capas extensas, donde satura el ritmo de acumulación. Dicha transición ocurre cuando la concentración de dañado supera cierto valor límite, el cual es independiente de las condiciones de implantación. Cuando se implantan los iones a temperaturas relativamente altas, el recocido dinámico cura el dañado previamente introducido y se establece una competición entre la generación de dañado y su disolución. Estos efectos se vuelven especialmente importantes para iones ligeros, como el B, el cual crea dañado más diluido, pequeño y distribuido de manera diferente que el causado por la implantación de iones más pesados, como el Ge. Esta descripción reproduce satisfactoriamente la cantidad de dañado y la extensión de las capas amorfas causadas por implantación iónica reportadas en la bibliografía. La velocidad de recristalización de la muestra previamente amorfizada depende fuertemente de la orientación del sustrato. El modelo LKMC presentado ha sido capaz de explicar estas diferencias entre orientaciones a través de un simple modelo, dominado por una única energía de activación y diferentes prefactores en las frecuencias de SPER dependiendo de las configuraciones de vecinos de los átomos que recristalizan. La formación de maclas aparece como una consecuencia de esta descripción, y es predominante en sustratos crecidos en la orientación (111)Ge. Este modelo es capaz de reproducir resultados experimentales para diferentes orientaciones, temperaturas y tiempos de evolución de la intercara amorfo/cristalina reportados por diferentes autores. Las parametrizaciones preliminares realizadas de los tensores de activación de tensiones son también capaces de proveer una buena correlación entre las simulaciones y los resultados experimentales de velocidad de SPER a diferentes temperaturas bajo una presión hidrostática aplicada. Los estudios presentados en esta tesis han ayudado a alcanzar un mejor entendimiento de los mecanismos de producción de dañado, su evolución, amorfización y SPER para Ge, además de servir como una útil herramienta para continuar el trabajo en este campo. In the recent years, Ge has regained attention to be integrated into existing microelectronic technologies. Even though it is not thought to be a feasible full replacement to Si in the near future, it will likely serve as an excellent complement to enhance electrical properties in future devices, specially due to its high carrier mobilities. This integration requires a significant upgrade of the state-of-the-art of regular manufacturing processes. Simulation techniques, such as kinetic Monte Carlo (KMC) algorithms, provide an appealing environment to research and innovation in the field, specially in terms of time and funding costs. In the present study, KMC techniques are used, for the first time, to understand Ge front-end processing, specifically damage accumulation and amorphization produced by ion implantation and Solid Phase Epitaxial Regrowth (SPER) of the amorphized layers. First, Binary Collision Approximation (BCA) simulations are used to calculate the damage caused by every ion. The evolution of this damage over time is simulated using non-lattice, or Object, KMC (OKMC) in which only defects are considered. SPER is simulated through a Lattice KMC (LKMC) approach, being able to follow the evolution of the lattice atoms forming the amorphous/crystalline interface. With the amorphization model developed in this work, implemented into a multi-material process simulator, all these processes can be simulated. It has been possible to understand damage accumulation, from point defect generation up to full amorphous layers formation. This accumulation occurs in three differentiated regimes, starting at a slow formation rate of the damage regions, followed by a fast local relaxation of areas into the amorphous phase where both crystalline and amorphous phases coexist, ending in full amorphization of extended layers, where the accumulation rate saturates. This transition occurs when the damage concentration overcomes a certain threshold value, which is independent of the implantation conditions. When implanting ions at relatively high temperatures, dynamic annealing takes place, healing the previously induced damage and establishing a competition between damage generation and its dissolution. These effects become specially important for light ions, as B, for which the created damage is more diluted, smaller and differently distributed than that caused by implanting heavier ions, as Ge. This description successfully reproduces damage quantity and extension of amorphous layers caused by means of ion implantation reported in the literature. Recrystallization velocity of the previously amorphized sample strongly depends on the substrate orientation. The presented LKMC model has been able to explain these differences between orientations through a simple model, dominated by one only activation energy and different prefactors for the SPER rates depending on the neighboring configuration of the recrystallizing atoms. Twin defects formation appears as a consequence of this description, and are predominant for (111)Ge oriented grown substrates. This model is able to reproduce experimental results for different orientations, temperatures and times of evolution of the amorphous/crystalline interface reported by different authors. Preliminary parameterizations for the activation strain tensors are able to also provide a good match between simulations and reported experimental results for SPER velocities at different temperatures under the appliance of hydrostatic pressure. The studies presented in this thesis have helped to achieve a greater understanding of damage generation, evolution, amorphization and SPER mechanisms in Ge, and also provide a useful tool to continue research in this field.

Solvent dependence of dynamic transitions in protein solutions

A transition as a function of increasing temperature from harmonic to anharmonic dynamics has been observed in globular proteins by using spectroscopic, scattering, and computer simulation techniques. We present here results of a dynamic neutron scattering analysis of the solvent dependence of the picosecond-time scale dynamic transition behavior of solutions of a simple single-subunit enzyme, xylanase. The protein is examined in powder form, in D2O, and in four two-component perdeuterated single-phase cryosolvents in which it is active and stable. The scattering profiles of the mixed solvent systems in the absence of protein are also determined. The general features of the dynamic transition behavior of the protein solutions follow those of the solvents. The dynamic transition in all of the mixed cryosolvent–protein systems is much more gradual than in pure D2O, consistent with a distribution of energy barriers. The differences between the dynamic behaviors of the various cryosolvent protein solutions themselves are remarkably small. The results are consistent with a picture in which the picosecond-time scale atomic dynamics respond strongly to melting of pure water solvent but are relatively invariant in cryosolvents of differing compositions and melting points.

Análise do aproveitamento múltiplo do reservatório de Barra Bonita - SP, através da aplicação de técnica de programação linear associada a modelo de rede de fluxo

O objeto deste trabalho é a análise do aproveitamento múltiplo do reservatório de Barra Bonita, localizado na confluência entre os rios Piracicaba e Tietê, no estado de São Paulo e pertencente ao chamado sistema Tietê-Paraná. Será realizada a otimização da operação do reservatório, através de programação linear, com o objetivo de aumentar a geração de energia elétrica, através da maximização da vazão turbinada. Em seguida, a partir dos resultados da otimização da geração de energia, serão utilizadas técnicas de simulação computacional, para se obter índices de desempenho conhecidos como confiabilidade, resiliência e vulnerabilidade, além de outros fornecidos pelo próprio modelo de simulação a ser utilizado. Estes índices auxiliam a avaliação da freqüência, magnitude e duração dos possíveis conflitos existentes. Serão analisados os possíveis conflitos entre a navegação, o armazenamento no reservatório, a geração de energia e a ocorrência de enchentes na cidade de Barra Bonita, localizada a jusante da barragem.

A multi-scaled approach for simulating chemical reaction systems

In this paper we give an overview of some very recent work, as well as presenting a new approach, on the stochastic simulation of multi-scaled systems involving chemical reactions. In many biological systems (such as genetic regulation and cellular dynamics) there is a mix between small numbers of key regulatory proteins, and medium and large numbers of molecules. In addition, it is important to be able to follow the trajectories of individual molecules by taking proper account of the randomness inherent in such a system. We describe different types of simulation techniques (including the stochastic simulation algorithm, Poisson Runge–Kutta methods and the balanced Euler method) for treating simulations in the three different reaction regimes: slow, medium and fast. We then review some recent techniques on the treatment of coupled slow and fast reactions for stochastic chemical kinetics and present a new approach which couples the three regimes mentioned above. We then apply this approach to a biologically inspired problem involving the expression and activity of LacZ and LacY proteins in E. coli, and conclude with a discussion on the significance of this work.

Molecular dynamics simulations of the hydrophobin SC3 at a hydrophobic/hydrophilic interface

Hydrophobins are small (similar to 100 aa) proteins that have an important role in the growth and development of mycelial fungi. They are surface active and, after secretion by the fungi, self-assemble into amphipathic membranes at hydrophobic/hydrophilic interfaces, reversing the hydrophobicity of the surface. In this study, molecular dynamics simulation techniques have been used to model the process by which a specific class I hydrophobin, SC3, binds to a range of hydrophobic/ hydrophilic interfaces. The structure of SC3 used in this investigation was modeled based on the crystal structure of the class II hydrophobin HFBII using the assumption that the disulfide pairings of the eight conserved cysteine residues are maintained. The proposed model for SC3 in aqueous solution is compact and globular containing primarily P-strand and coil structures. The behavior of this model of SC3 was investigated at an air/water, an oil/water, and a hydrophobic solid/water interface. It was found that SC3 preferentially binds to the interfaces via the loop region between the third and fourth cysteine residues and that binding is associated with an increase in a-helix formation in qualitative agreement with experiment. Based on a combination of the available experiment data and the current simulation studies, we propose a possible model for SC3 self-assembly on a hydrophobic solid/water interface.

Evaluating the impact of design decisions on the financial performance of manufacturing companies

Product design decisions can have a significant impact on the financial and operation performance of manufacturing companies. Therefore good analysis of the financial impact of design decisions is required if the profitability of the business is to be maximised. The product design process can be viewed as a chain of decisions which links decisions about the concept to decisions about the detail. The idea of decision chains can be extended to include the design and operation of the 'downstream' business processes which manufacture and support the product. These chains of decisions are not independent but are interrelated in a complex manner. To deal with the interdependencies requires a modelling approach which represents all the chains of decisions, to a level of detail not normally considered in the analysis of product design. The operational, control and financial elements of a manufacturing business constitute a dynamic system. These elements interact with each other and with external elements (i.e. customers and suppliers). Analysing the chain of decisions for such an environment requires the application of simulation techniques, not just to any one area of interest, but to the whole business i.e. an enterprise simulation. To investigate the capability and viability of enterprise simulation an experimental 'Whole Business Simulation' system has been developed. This system combines specialist simulation elements and standard operational applications software packages, to create a model that incorporates all the key elements of a manufacturing business, including its customers and suppliers. By means of a series of experiments, the performance of this system was compared with a range of existing analysis tools (i.e. DFX, capacity calculation, shop floor simulator, and business planner driven by a shop floor simulator).

Modelling human performance within manufacturing systems design:from a theoretical towards a practical framework

Computer-based simulation is frequently used to evaluate the capabilities of proposed manufacturing system designs. Unfortunately, the real systems are often found to perform quite differently from simulation predictions and one possible reason for this is an over-simplistic representation of workers' behaviour within current simulation techniques. The accuracy of design predictions could be improved through a modelling tool that integrates with computer-based simulation and incorporates the factors and relationships that determine workers' performance. This paper explores the viability of developing a similar tool based on our previously published theoretical modelling framework. It focuses on evolving this purely theoretical framework towards a practical modelling tool that can actually be used to expand the capabilities of current simulation techniques. Based on an industrial study, the paper investigates how the theoretical framework works in practice, analyses strengths and weaknesses in its formulation, and proposes developments that can contribute towards enabling human performance modelling in a practical way.

Monte Carlo and molecular dynamics simulations of methane in potassium montmorillonite clay hydrates at elevated pressures and temperatures

The structure and dynamics of methane in hydrated potassium montmorillonite clay have been studied under conditions encountered in sedimentary basin and compared to those of hydrated sodium montmorillonite clay using computer simulation techniques. The simulated systems contain two molecular layers of water and followed gradients of 150 barkm-1 and 30 Kkm-1 up to a maximum burial depth of 6 km. Methane particle is coordinated to about 19 oxygen atoms, with 6 of these coming from the clay surface oxygen. Potassium ions tend to move away from the center towards the clay surface, in contrast to the behavior observed with the hydrated sodium form. The clay surface affinity for methane was found to be higher in the hydrated K-form. Methane diffusion in the two-layer hydrated K-montmorillonite increases from 0.39×10-9 m2s-1 at 280 K to 3.27×10-9 m2s-1 at 460 K compared to 0.36×10-9 m2s-1 at 280 K to 4.26×10-9 m2s-1 at 460 K in Na-montmorillonite hydrate. The distributions of the potassium ions were found to vary in the hydrates when compared to those of sodium form. Water molecules were also found to be very mobile in the potassium clay hydrates compared to sodium clay hydrates. © 2004 Elsevier Inc. All All rights reserved.

Modelagem numérica de uma estrutura de contenção de estacas espaçadas atirantadas em areia

Retaining walls design involves factors such as plastification, loading and unloading, pre-stressing, excessive displacements and earth and water thrust. Furthermore, the interaction between the retained soil and the structure is rather complex and hard to predict. Despite the advances in numerical simulation techniques and monitoring of forces and displacements with field instrumentation, design projects are still based on classical methods, whose simplifying assumptions may overestimate structural elements of the retaining wall. This dissertation involves a three-dimensional numerical study on the behavior of a retaining wall using the finite element method (FEM). The retaining wall structure is a contiguous bored pile wall with tie-back anchors. The numerical results were compared to data obtained from field instrumentation. The influence of the position of one or two layers of anchors and the effects of the construction of a slab bounded at the top of the retaining wall was evaluated. Furthermore, this study aimed at investigating the phenomenon of arching in the soil behind the wall. Arching was evaluated by analyzing the effects of pile spacing on horizontal stresses and displacements. Parametric analysis with one layers of anchors showed that the smallest horizontal displacements of the structure were achieved for between 0.3 and 0.5 times the excavation depth. Parametric analyses with two anchor layers showed that the smallest horizontal displacements were achieve for anchors positioned in depths of 0.4H and 0.7H. The construction of a slab at the top of the retaining wall decreased the horizontal displacements by 0.14% times the excavation depth as compared to analyses without the slab. With regard to the arching , analyzes showed an optimal range of spacing between the faces of the piles between 0.4 and 0.6 times the diameter of the pile