Scale model research for room acoustics purposes

In the field of Room Acoustics it is common using scale models to study a room. Through this method it is possible to predict its behavior, which may be very useful to detect and correct any problem prior to build it, saving many resources. Nowadays this method has been relegated to a secondary position due to the peak of simulation software, which makes possible studying rooms in a cheap, flexible and simple way, as well as it is potentially less time consuming. Nevertheless, the scale model method is still under study, as it may give some additional information. This project intends to focus in pedagogic possibilities of the scale model method. This method offers the student the opportunity of study and grasp some of the most important phenomena in Room Acoustics, in a more intuitive way than just a software simulation. Furthermore most of the existing software in this field is aimed to the technician working in the lab, as efficiently as possible, not to the student trying to understand and learn something. Here, the facilities and resources of Syddansk Universitet regarding this matter will be studied and evaluated, as well as the procedure for the experiments, paying special attention not only to its reliability and accuracy, but also to its didactic possibilities. Besides, if possible, any improvement that could help to enhance any of the listed aspects will be suggested. En el ámbito de la Acústica Arquitectónica es común el uso de modelos a escala para estudiar un recinto determinado. Mediante esta técnica es posible por ejemplo predecir el comportamiento del recinto y detectar problemas antes de su construcción, con el consecuente ahorro de recursos. Actualmente el uso de modelos a escala está desplazado a un segundo plano por el uso de software simulación, debido a la sencillez y flexibilidad que puede aportar la simulación por ordenador, así como a la economía de tiempo y recursos que supone. Sin embargo sigue siendo objeto de estudio, dado que puede aportar información muy valiosa para el ingeniero. Este proyecto se centra en las posibilidades pedagógicas de dicho método. El uso de modelos a escala brinda la oportunidad a los estudiantes de estudiar y comprender algunos de los fenómenos más importantes en la Acústica Arquitectónica de una forma más directa e intuitiva que una simulación por ordenador. Se pretende estudiar y evaluar los medios al alcance de los estudiantes en la Syddansk Universitet, así como los métodos usados, atendiendo no sólo a su precisión y fiabilidad, si no a su potencial pedagógico. Así mismo, si es posible, se propondrán cambios que puedan suponer una mejora en cualquiera de estos aspectos. Así el proyecto se divide en varias secciones claramente diferenciadas. En el apartado Background and Theoretical Basis se introduce el tema del estudio y simulación de recintos acústicos. Se explica su importancia y utilidad, y se comenta la situación actual de estas técnicas, abordando diferentes métodos usados así como sus bases teóricas y principales ventajas e inconvenientes. Bajo el apartado de Project se analizan diferentes factores relacionados con el problema. Se estudian los recursos a disposición del alumno, desde el software y hardware implicados hasta el equipo de medida y otros recursos necesarios para la realización de las prácticas. Es en esta parte donde se centra la parte más importante del trabajo, consistente en la medición y comprobación de las características más relevantes del equipo implicado. Haciendo posible así confirmar su validez y precisión, tanto desde el punto de vista técnico como pedagógico, así como estableciendo los límites dentro de los que se puede considerar fiable el modelo. Al final de este apartado se aborda la influencia de la absorción del aire en altas frecuencias, y la variación en los coeficientes de absorción y dispersión de los materiales respecto de la frecuencia. Por último se realiza una verificación subjetiva del sistema completo, debido a que por limitaciones técnicas no ha sido posible evaluar el montaje en el rango equivalente a toda la banda audible, y que los métodos estudiados tienen como meta última asegurar una buena percepción por parte del oyente en el recinto dado. Dentro del apartado Conclusions se hace un breve resumen de las conclusiones extraídas anteriormente, y se valora el rendimiento y utilidad general del modelo, que a pesar de algunos problemas de precisión y repetibilidad lógicos debido a los medios usados, es válido para ilustrar los fenómenos físicos que se quieren enseñar al alumno. En la sección de Future Work se proponen diferentes vías de trabajo para futuros proyectos en la Syddansk Universitet que podrían ser útiles confirmar el trabajo realizado en este proyecto, mejorar la precisión y fiabilidad del montaje o enriquecer las posibilidades pedagógicas de las prácticas relacionadas. Por último se encuentra, tras el apartado de referencias, los anexos con tablas y gráficas relativas a las medidas realizadas en diferentes partes del trabajo. También se puede encontrar información y material relacionado con el proyecto en el CD adjunto.

Use of Feynman diagrams in large-scale neural networks with nonlinear behaviour

A new proposal to the study of large-scale neural networks is reported. It is based on the use of similar graphs to the Feynman diagrams. A first general theory is presented and some interpretations are given. A propagator, based on the Green's function of the neuron, is the basis of the method. Application to a simple case is reported.

Analysis of large-scale digital optical neural networks by Feynman diagrams

A new method to study large scale neural networks is presented in this paper. The basis is the use of Feynman- like diagrams. These diagrams allow the analysis of collective and cooperative phenomena with a similar methodology to the employed in the Many Body Problem. The proposed method is applied to a very simple structure composed by an string of neurons with interaction among them. It is shown that a new behavior appears at the end of the row. This behavior is different to the initial dynamics of a single cell. When a feedback is present, as in the case of the hippocampus, this situation becomes more complex with a whole set of new frequencies, different from the proper frequencies of the individual neurons. Application to an optical neural network is reported.

An interactive method of fuzzy probability elicitation in risk analysis

Expert knowledge is used to assign probabilities to events in many risk analysis models. However, experts sometimes find it hard to provide specific values for these probabilities, preferring to express vague or imprecise terms that are mapped using a previously defined fuzzy number scale. The rigidity of these scales generates bias in the probability elicitation process and does not allow experts to adequately express their probabilistic judgments. We present an interactive method for extracting a fuzzy number from experts that represents their probabilistic judgments for a given event, along with a quality measure of the probabilistic judgments, useful in a final information filtering and analysis sensitivity process.

Large scale multiphysics modeling of neurites

Situado en el límite entre Ingeniería, Informática y Biología, la mecánica computacional de las neuronas aparece como un nuevo campo interdisciplinar que potencialmente puede ser capaz de abordar problemas clínicos desde una perspectiva diferente. Este campo es multiescala por naturaleza, yendo desde la nanoescala (como, por ejemplo, los dímeros de tubulina) a la macroescala (como, por ejemplo, el tejido cerebral), y tiene como objetivo abordar problemas que son complejos, y algunas veces imposibles, de estudiar con medios experimentales. La modelización computacional ha sido ampliamente empleada en aplicaciones Neurocientíficas tan diversas como el crecimiento neuronal o la propagación de los potenciales de acción compuestos. Sin embargo, en la mayoría de los enfoques de modelización hechos hasta ahora, la interacción entre la célula y el medio/estímulo que la rodea ha sido muy poco explorada. A pesar de la tremenda importancia de esa relación en algunos desafíos médicos—como, por ejemplo, lesiones traumáticas en el cerebro, cáncer, la enfermedad del Alzheimer—un puente que relacione las propiedades electrofisiológicas-químicas y mecánicas desde la escala molecular al nivel celular todavía no existe. Con ese objetivo, esta investigación propone un marco computacional multiescala particularizado para dos escenarios respresentativos: el crecimiento del axón y el acomplamiento electrofisiológicomecánico de las neuritas. En el primer caso, se explora la relación entre los constituyentes moleculares del axón durante su crecimiento y sus propiedades mecánicas resultantes, mientras que en el último, un estímulo mecánico provoca deficiencias funcionales a nivel celular como consecuencia de sus alteraciones electrofisiológicas-químicas. La modelización computacional empleada en este trabajo es el método de las diferencias finitas, y es implementada en un nuevo programa llamado Neurite. Aunque el método de los elementos finitos es también explorado en parte de esta investigación, el método de las diferencias finitas tiene la flexibilidad y versatilidad necesaria para implementar mode los biológicos, así como la simplicidad matemática para extenderlos a simulaciones a gran escala con un coste computacional bajo. Centrándose primero en el efecto de las propiedades electrofisiológicas-químicas sobre las propiedades mecánicas, una versión adaptada de Neurite es desarrollada para simular la polimerización de los microtúbulos en el crecimiento del axón y proporcionar las propiedades mecánicas como función de la ocupación de los microtúbulos. Después de calibrar el modelo de crecimiento del axón frente a resultados experimentales disponibles en la literatura, las características mecánicas pueden ser evaluadas durante la simulación. Las propiedades mecánicas del axón muestran variaciones dramáticas en la punta de éste, donde el cono de crecimiento soporta las señales químicas y mecánicas. Bansándose en el conocimiento ganado con el modelo de diferencias finitas, y con el objetivo de ir de 1D a 3D, este esquema preliminar pero de una naturaleza innovadora allana el camino a futuros estudios con el método de los elementos finitos. Centrándose finalmente en el efecto de las propiedades mecánicas sobre las propiedades electrofisiológicas- químicas, Neurite es empleado para relacionar las cargas mecánicas macroscópicas con las deformaciones y velocidades de deformación a escala microscópica, y simular la propagación de la señal eléctrica en las neuritas bajo carga mecánica. Las simulaciones fueron calibradas con resultados experimentales publicados en la literatura, proporcionando, por tanto, un modelo capaz de predecir las alteraciones de las funciones electrofisiológicas neuronales bajo cargas externas dañinas, y uniendo lesiones mecánicas con las correspondientes deficiencias funcionales. Para abordar simulaciones a gran escala, aunque otras arquitecturas avanzadas basadas en muchos núcleos integrados (MICs) fueron consideradas, los solvers explícito e implícito se implementaron en unidades de procesamiento central (CPU) y unidades de procesamiento gráfico (GPUs). Estudios de escalabilidad fueron llevados acabo para ambas implementaciones mostrando resultados prometedores para casos de simulaciones extremadamente grandes con GPUs. Esta tesis abre la vía para futuros modelos mecánicos con el objetivo de unir las propiedades electrofisiológicas-químicas con las propiedades mecánicas. El objetivo general es mejorar el conocimiento de las comunidades médicas y de bioingeniería sobre la mecánica de las neuronas y las deficiencias funcionales que aparecen de los daños producidos por traumatismos mecánicos, como lesiones traumáticas en el cerebro, o enfermedades neurodegenerativas como la enfermedad del Alzheimer. ABSTRACT Sitting at the interface between Engineering, Computer Science and Biology, Computational Neuron Mechanics appears as a new interdisciplinary field potentially able to tackle clinical problems from a new perspective. This field is multiscale by nature, ranging from the nanoscale (e.g., tubulin dimers) to the macroscale (e.g., brain tissue), and aims at tackling problems that are complex, and sometime impossible, to study through experimental means. Computational modeling has been widely used in different Neuroscience applications as diverse as neuronal growth or compound action potential propagation. However, in the majority of the modeling approaches done in this field to date, the interactions between the cell and its surrounding media/stimulus have been rarely explored. Despite of the tremendous importance of such relationship in several medical challenges—e.g., traumatic brain injury (TBI), cancer, Alzheimer’s disease (AD)—a bridge between electrophysiological-chemical and mechanical properties of neurons from the molecular scale to the cell level is still lacking. To this end, this research proposes a multiscale computational framework particularized for two representative scenarios: axon growth and electrophysiological-mechanical coupling of neurites. In the former case, the relation between the molecular constituents of the axon during its growth and its resulting mechanical properties is explored, whereas in the latter, a mechanical stimulus provokes functional deficits at cell level as a consequence of its electrophysiological-chemical alterations. The computational modeling approach chosen in this work is the finite difference method (FDM), and was implemented in a new program called Neurite. Although the finite element method (FEM) is also explored as part of this research, the FDM provides the necessary flexibility and versatility to implement biological models, as well as the mathematical simplicity to extend them to large scale simulations with a low computational cost. Focusing first on the effect of electrophysiological-chemical properties on the mechanical proper ties, an adaptation of Neurite was developed to simulate microtubule polymerization in axonal growth and provide the axon mechanical properties as a function of microtubule occupancy. After calibrating the axon growth model against experimental results available in the literature, the mechanical characteristics can be tracked during the simulation. The axon mechanical properties show dramatic variations at the tip of the axon, where the growth cone supports the chemical and mechanical signaling. Based on the knowledge gained from the FDM scheme, and in order to go from 1D to 3D, this preliminary yet novel scheme paves the road for future studies with FEM. Focusing then on the effect of mechanical properties on the electrophysiological-chemical properties, Neurite was used to relate macroscopic mechanical loading to microscopic strains and strain rates, and simulate the electrical signal propagation along neurites under mechanical loading. The simulations were calibrated against experimental results published in the literature, thus providing a model able to predict the alteration of neuronal electrophysiological function under external damaging load, and linking mechanical injuries to subsequent acute functional deficits. To undertake large scale simulations, although other state-of-the-art architectures based on many integrated cores (MICs) were considered, the explicit and implicit solvers were implemented for central processing units (CPUs) and graphics processing units (GPUs). Scalability studies were done for both implementations showing promising results for extremely large scale simulations with GPUs. This thesis opens the avenue for future mechanical modeling approaches aimed at linking electrophysiological- chemical properties to mechanical properties. Its overarching goal is to enhance the bioengineering and medical communities knowledge on neuronal mechanics and functional deficits arising from damages produced by direct mechanical insults, such as TBI, or neurodegenerative evolving illness, such as AD.

A Special Perturbation Method in Orbital Dynamics

Bead models are used in dynamical simulation of tethers. These models discretize a cable using beads distributed along its length. The time evolution is obtained nu- merically. Typically the number of particles ranges between 5 and 50, depending on the required accuracy. Sometimes the simulation is extended over long periods (several years). The complex interactions between the cable and its spatial environment require to optimize the propagators —both in runtime and precisión that constitute the central core of the process. The special perturbation method treated on this article conjugates simpleness of computer implementation, speediness and precision, and is capable to propagate the orbit of whichever material particle. The paper describes the evolution of some orbital elements, which are constants in a non-perturbed problem, but which evolve in the time scale imposed by the perturbation. It can be used with any kind of orbit and it is free of sin- gularities related to small inclination and/or small eccentricity. The use of Euler parameters makes it robust.

Use of the energy-release rate in a 2 scale damage analysis of a bonded joint

Stress singularities appear at the extremities of an adhesive bond. They can produce a damage mechanism that we assimilate in this Note to a crack. The energy release rate permits to characterize its evolution. But a very refined mesh would be necessary for a real structure. Using an asymptotic method based on the small thickness of the bond a limit model with a different local behaviour is suggested. It leads to an approximation of the energy release rate

Determination of critical slip surfaces using mutative scale chaos optimization

Limit equilibrium is a common method used to analyze the stability of a slope, and minimization of the factor of safety or identification of critical slip surfaces is a classical geotechnical problem in the context of limit equilibrium methods for slope stability analyses. A mutative scale chaos optimization algorithm is employed in this study to locate the noncircular critical slip surface with Spencer’s method being employed to compute the factor of safety. Four examples from the literature—one homogeneous slope and three layered slopes—are employed to identify the efficiency and accuracy of this approach. Results indicate that the algorithm is flexible and that although it does not generally provide the minimum FS, it provides results that are close to the minimum, an improvement over other solutions proposed in the literature and with small relative errors with respect to other minimum factor of safety (FS) values reported in the literature.

Diseño y construcción de una mini-turbina eólica

Dado que es difícil imaginar en el futuro una sociedad moderna donde la energía no juegue un papel fundamental y puesto que numerosos estudios han demostrado que el ritmo actual de consumo de combustibles es insostenible y perjudicial para la vida del planeta, es fundamental concienciar a la humanidad de que un cambio de tendencia no solo es necesario sino que es imperativo. No se trata de erradicar por completo el uso de fuentes de carácter fósil, pues en muchos países es su principal o incluso su única forma de obtener energía, sino de avanzar hacia un equilibrio en la generación, para lo que será vital permitir el desarrollo de energías limpias, aumentar la eficiencia de la tecnología y reducir el consumo. En este contexto se ha decidido construir un rotor eólico de pequeñas dimensiones que servirá como herramienta de estudio para alumnos de ingeniería. Para diseñar la turbina se ha desarrollado un modelo de programación informática que, basado en conceptos aerodinámicos, permite calcular la geometría de las palas en función de unas condiciones iniciales, estimar la potencia del rotor y obtener sus curvas de funcionamiento. Uno de los principales problemas de la tecnología eólica es su alta variabilidad, por ello se ha implementado un sistema de regulación de velocidad; se trata de un mecanismo que actúa sobre la orientación de las palas y permite regular la potencia de un generador eléctrico acoplado al rotor. Los aerogeneradores actuales recurren a este tipo de sistemas para tratar de suavizar los desequilibrios de potencia que puedan producir las ráfagas de viento. Se ha recurrido a un software de diseño asistido por ordenador para dibujar tanto el rotor como el sistema de regulación de velocidad. La mayoría de las piezas del rotor se han fabricado con ayuda de una impresora 3D, otras, las metálicas, se han tallado en aluminio mediante un torno. Aunque el programa informático que realiza los cálculos aerodinámicos devuelve datos teóricos a cerca del comportamiento del rotor, se ha creído necesario probar el molino mediante ensayos de laboratorio a fin de obtener un resultado más realista.Abstract Given that it’s difficult to imagine any modern society in the future where energy does not play a crucial role, and as many studies have shown that the actual rate of fuel consumption is unsustainable and harmful to life on the planet, it is essential to raise mankind’s awareness that a change in the current trend is not only necessary, but is also imperative. It is not a question of completely eradicating the use of fossil fuels, as in many countries they are the main or even the only way of generating energy, but rather working towards a balance in generation. To do so it is vital to encourage the development of clean energies, increase technological efficiency and reduce consumption. In view of this we have decided to build a small scale wind turbine rotor which can be used as a study tool for engineering students. To design the turbine a software programme was developed based on aerodynamic concepts, which allows us to calculate the geometry of the blades depending on certain initial conditions, estimate the power of the turbine, and obtain performance curves. One of the main issues with wind technology is its high variability, and therefore we implemented a speed regulation system consisting of a mechanism that varies the orientation of the blades and thus allows us to regulate the power of an electric generator attached to the turbine. Current wind powered generators use this type of system to try to smooth out spikes in power that may be caused by gusts of wind. We have used CAD software to design both the turbine itself and the speed regulation system. Most of the turbine parts have been manufactured with the aid of a 3D printer, while the other metallic parts have been turned on made a lathe in aluminum. Although the software programme which calculates the aerodynamics provide us theoretical data about the operation of the rotor. We consider it necessary to test the wind turbine in a lab to obtain more accurate results.

Guidelines for the design of an environmental flow regime program at the regional scale: Application of the ELOHA framework in the Ebro River basin

La gestión de los recursos hídricos se convierte en un reto del presente y del futuro frente a un panorama de continuo incremento de la demanda de agua debido al crecimiento de la población, el crecimiento del desarrollo económico y los posibles efectos del calentamiento global. La política hidráulica desde los años 60 en España se ha centrado en la construcción de infraestructuras que han producido graves alteraciones en el régimen natural de los ríos. Estas alteraciones han provocado y acrecentado los impactos sobre los ecosistemas fluviales y ribereños. Desde los años 90, sin embargo, ha aumentado el interés de la sociedad para conservar estos ecosistemas. El concepto de caudales ambientales consiste en un régimen de caudales que simula las características principales del régimen natural. Los caudales ambientales están diseñados para conservar la estructura y funcionalidad de los ecosistemas asociados al régimen fluvial, bajo la hipótesis de que los elementos que conforman estos ecosistemas están profundamente adaptados al régimen natural de caudales, y que cualquier alteración del régimen natural puede provocar graves daños a todo el sistema. El método ELOHA (Ecological Limits of Hydrological Alteration) tiene como finalidad identificar las componentes del régimen natural de caudales que son clave para mantener el equilibrio de los ecosistemas asociados, y estimar los límites máximos de alteración de estas componentes para garantizar su buen estado. Esta tesis presenta la aplicación del método ELOHA en la cuenca del Ebro. La cuenca del Ebro está profundamente regulada e intervenida por el hombre, y sólo las cabeceras de los principales afluentes del Ebro gozan todavía de un régimen total o cuasi natural. La tesis se estructura en seis capítulos que desarrollan las diferentes partes del método. El primer capítulo explica cómo se originó el concepto “caudales ambientales” y en qué consiste el método ELOHA. El segundo capítulo describe el área de estudio. El tercer capítulo realiza una clasificación de los regímenes naturales de la cuenca (RNC) del Ebro, basada en series de datos de caudal mínimamente alterado y usando exclusivamente parámetros hidrológicos. Se identificaron seis tipos diferentes de régimen natural: pluvial mediterráneo, nivo-pluvial, pluvial mediterréaneo con una fuerte componente del caudal base, pluvial oceánico, pluvio-nival oceánico y Mediterráneo. En el cuarto capítulo se realiza una regionalización a toda la cuenca del Ebro de los seis RNC encontrados en la cueca. Mediante parámetros climáticos y fisiográficos se extrapola la información del tipo de RNC a puntos donde no existen datos de caudal inalterado. El patrón geográfico de los tipos de régimen fluvial obtenido con la regionalización resultó ser coincidente con el patrón obtenido a través de la clasificación hidrológica. El quinto capítulo presenta la validación biológica de los procesos de clasificación anteriores: clasificación hidrológica y regionalización. La validación biológica de los tipos de regímenes fluviales es imprescindible, puesto que los diferentes tipos de régimen fluvial van a servir de unidades de gestión para favorecer el mantenimiento de los ecosistemas fluviales. Se encontraron diferencias significativas entre comunidades biológicas en cinco de los seis tipos de RNC encontrados en la cuenca. Finalmente, en el sexto capítulo se estudian las relaciones hidro-ecológicas existentes en tres de los seis tipos de régimen fluvial encontrados en la cuenca del Ebro. Mediante la construcción de curvas hidro-ecológicas a lo largo de un gradiente de alteración hidrológica, se pueden sugerir los límites de alteración hidrológica (ELOHAs) para garantizar el buen estado ecológico en cada uno de los tipos fluviales estudiados. Se establecieron ELOHAs en tres de los seis tipos de RNC de la cuenca del Ebro Esta tesis, además, pone en evidencia la falta de datos biológicos asociados a registros de caudal. Para llevar a cabo la implantación de un régimen de caudales ambientales en la cuenca, la ubicación de los puntos de muestreo biológico cercanos a estaciones de aforo es imprescindible para poder extraer relaciones causa-efecto de la gestión hidrológica sobre los ecosistemas dependientes. ABSTRACT In view of a growing freshwater demand because of population raising, improvement of economies and the potential effects of climate change, water resources management has become a challenge for present and future societies. Water policies in Spain have been focused from the 60’s on constructing hydraulic infrastructures, in order to dampen flow variability and granting water availability along the year. Consequently, natural flow regimes have been deeply altered and so the depending habitats and its ecosystems. However, an increasing acknowledgment of societies for preserving healthy freshwater ecosystems started in the 90’s and agreed that to maintain healthy freshwater ecosystems, it was necessary to set environmental flow regimes based on the natural flow variability. The Natural Flow Regime paradigm (Richter et al. 1996, Poff et al. 1997) bases on the hypothesis that freshwater ecosystems are made up by elements adapted to natural flow conditions, and any change on these conditions can provoke deep impacts on the whole system. Environmental flow regime concept consists in designing a flow regime that emulates natural flow characteristics, so that ecosystem structure, functions and services are maintained. ELOHA framework (Ecological Limits of Hydrological Alteration) aims to identify key features of the natural flow regime (NFR) that are needed to maintain and preserve healthy freshwater and riparian ecosystems. Moreover, ELOHA framework aims to quantify thresholds of alteration of these flow features according to ecological impacts. This thesis describes the application of the ELOHA framework in the Ebro River Basin. The Ebro River basin is the second largest basin in Spain and it is highly regulated for human demands. Only the Ebro headwaters tributaries still have completely unimpaired flow regime. The thesis has six chapters and the process is described step by step. The first chapter makes an introduction to the origin of the environmental flow concept and the necessity to come up. The second chapter shows a description of the study area. The third chapter develops a classification of NFRs in the basin based on natural flow data and using exclusively hydrological parameters. Six NFRs were found in the basin: continental Mediterranean-pluvial, nivo-pluvial, continental Mediterranean pluvial (with groundwater-dominated flow pattern), pluvio-oceanic, pluvio-nival-oceanic and Mediterranean. The fourth chapter develops a regionalization of the six NFR types across the basin by using climatic and physiographic variables. The geographical pattern obtained from the regionalization process was consistent with the pattern obtained with the hydrologic classification. The fifth chapter performs a biological validation of both classifications, obtained from the hydrologic classification and the posterior extrapolation. When the aim of flow classification is managing water resources according to ecosystem requirements, a validation based on biological data is compulsory. We found significant differences in reference macroinvertebrate communities between five over the six NFR types identified in the Ebro River basin. Finally, in the sixth chapter we explored the existence of significant and explicative flow alteration-ecological response relationships (FA-E curves) within NFR types in the Ebro River basin. The aim of these curves is to find out thresholds of hydrological alteration (ELOHAs), in order to preserve healthy freshwater ecosystem. We set ELOHA values in three NFR types identified in the Ebro River basin. During the development of this thesis, an inadequate biological monitoring in the Ebro River basin was identified. The design and establishment of appropriate monitoring arrangements is a critical final step in the assessment and implementation of environmental flows. Cause-effect relationships between hydrology and macroinvertebrate community condition are the principal data that sustain FA-E curves. Therefore, both data sites must be closely located, so that the effects of external factors are minimized. The scarce hydro-biological pairs of data available in the basin prevented us to apply the ELOHA method at all NFR types.

A subgrid viscosity Lagrance-Galerkin method for convection-diffusion problems

We present and analyze a subgrid viscosity Lagrange-Galerk in method that combines the subgrid eddy viscosity method proposed in W. Layton, A connection between subgrid scale eddy viscosity and mixed methods. Appl. Math. Comp., 133: 14 7-157, 2002, and a conventional Lagrange-Galerkin method in the framework of P1⊕ cubic bubble finite elements. This results in an efficient and easy to implement stabilized method for convection dominated convection diffusion reaction problems. Numerical experiments support the numerical analysis results and show that the new method is more accurate than the conventional Lagrange-Galerkin one.

Brownian dynamics simulations of protein folding: Access to milliseconds time scale and beyond

Protein folding occurs on a time scale ranging from milliseconds to minutes for a majority of proteins. Computer simulation of protein folding, from a random configuration to the native structure, is nontrivial owing to the large disparity between the simulation and folding time scales. As an effort to overcome this limitation, simple models with idealized protein subdomains, e.g., the diffusion–collision model of Karplus and Weaver, have gained some popularity. We present here new results for the folding of a four-helix bundle within the framework of the diffusion–collision model. Even with such simplifying assumptions, a direct application of standard Brownian dynamics methods would consume 10,000 processor-years on current supercomputers. We circumvent this difficulty by invoking a special Brownian dynamics simulation. The method features the calculation of the mean passage time of an event from the flux overpopulation method and the sampling of events that lead to productive collisions even if their probability is extremely small (because of large free-energy barriers that separate them from the higher probability events). Using these developments, we demonstrate that a coarse-grained model of the four-helix bundle can be simulated in several days on current supercomputers. Furthermore, such simulations yield folding times that are in the range of time scales observed in experiments.

Multiple-complete-digest restriction fragment mapping: Generating sequence-ready maps for large-scale DNA sequencing

Multiple-complete-digest mapping is a DNA mapping technique based on complete-restriction-digest fingerprints of a set of clones that provides highly redundant coverage of the mapping target. The maps assembled from these fingerprints order both the clones and the restriction fragments. Maps are coordinated across three enzymes in the examples presented. Starting with yeast artificial chromosome contigs from the 7q31.3 and 7p14 regions of the human genome, we have produced cosmid-based maps spanning more than one million base pairs. Each yeast artificial chromosome is first subcloned into cosmids at a redundancy of ×15–30. Complete-digest fragments are electrophoresed on agarose gels, poststained, and imaged on a fluorescent scanner. Aberrant clones that are not representative of the underlying genome are rejected in the map construction process. Almost every restriction fragment is ordered, allowing selection of minimal tiling paths with clone-to-clone overlaps of only a few thousand base pairs. These maps demonstrate the practicality of applying the experimental and software-based steps in multiple-complete-digest mapping to a target of significant size and complexity. We present evidence that the maps are sufficiently accurate to validate both the clones selected for sequencing and the sequence assemblies obtained once these clones have been sequenced by a “shotgun” method.

Large-scale protein structure modeling of the Saccharomyces cerevisiae genome

The function of a protein generally is determined by its three-dimensional (3D) structure. Thus, it would be useful to know the 3D structure of the thousands of protein sequences that are emerging from the many genome projects. To this end, fold assignment, comparative protein structure modeling, and model evaluation were automated completely. As an illustration, the method was applied to the proteins in the Saccharomyces cerevisiae (baker’s yeast) genome. It resulted in all-atom 3D models for substantial segments of 1,071 (17%) of the yeast proteins, only 40 of which have had their 3D structure determined experimentally. Of the 1,071 modeled yeast proteins, 236 were related clearly to a protein of known structure for the first time; 41 of these previously have not been characterized at all.

Linking genome and proteome by mass spectrometry: Large-scale identification of yeast proteins from two dimensional gels

The function of many of the uncharacterized open reading frames discovered by genomic sequencing can be determined at the level of expressed gene products, the proteome. However, identifying the cognate gene from minute amounts of protein has been one of the major problems in molecular biology. Using yeast as an example, we demonstrate here that mass spectrometric protein identification is a general solution to this problem given a completely sequenced genome. As a first screen, our strategy uses automated laser desorption ionization mass spectrometry of the peptide mixtures produced by in-gel tryptic digestion of a protein. Up to 90% of proteins are identified by searching sequence data bases by lists of peptide masses obtained with high accuracy. The remaining proteins are identified by partially sequencing several peptides of the unseparated mixture by nanoelectrospray tandem mass spectrometry followed by data base searching with multiple peptide sequence tags. In blind trials, the method led to unambiguous identification in all cases. In the largest individual protein identification project to date, a total of 150 gel spots—many of them at subpicomole amounts—were successfully analyzed, greatly enlarging a yeast two-dimensional gel data base. More than 32 proteins were novel and matched to previously uncharacterized open reading frames in the yeast genome. This study establishes that mass spectrometry provides the required throughput, the certainty of identification, and the general applicability to serve as the method of choice to connect genome and proteome.