The information bottleneck method for genome-wide association studies

In population studies, most current methods focus on identifying one outcome-related SNP at a time by testing for differences of genotype frequencies between disease and healthy groups or among different population groups. However, testing a great number of SNPs simultaneously has a problem of multiple testing and will give false-positive results. Although, this problem can be effectively dealt with through several approaches such as Bonferroni correction, permutation testing and false discovery rates, patterns of the joint effects by several genes, each with weak effect, might not be able to be determined. With the availability of high-throughput genotyping technology, searching for multiple scattered SNPs over the whole genome and modeling their joint effect on the target variable has become possible. Exhaustive search of all SNP subsets is computationally infeasible for millions of SNPs in a genome-wide study. Several effective feature selection methods combined with classification functions have been proposed to search for an optimal SNP subset among big data sets where the number of feature SNPs far exceeds the number of observations. ^ In this study, we take two steps to achieve the goal. First we selected 1000 SNPs through an effective filter method and then we performed a feature selection wrapped around a classifier to identify an optimal SNP subset for predicting disease. And also we developed a novel classification method-sequential information bottleneck method wrapped inside different search algorithms to identify an optimal subset of SNPs for classifying the outcome variable. This new method was compared with the classical linear discriminant analysis in terms of classification performance. Finally, we performed chi-square test to look at the relationship between each SNP and disease from another point of view. ^ In general, our results show that filtering features using harmononic mean of sensitivity and specificity(HMSS) through linear discriminant analysis (LDA) is better than using LDA training accuracy or mutual information in our study. Our results also demonstrate that exhaustive search of a small subset with one SNP, two SNPs or 3 SNP subset based on best 100 composite 2-SNPs can find an optimal subset and further inclusion of more SNPs through heuristic algorithm doesn't always increase the performance of SNP subsets. Although sequential forward floating selection can be applied to prevent from the nesting effect of forward selection, it does not always out-perform the latter due to overfitting from observing more complex subset states. ^ Our results also indicate that HMSS as a criterion to evaluate the classification ability of a function can be used in imbalanced data without modifying the original dataset as against classification accuracy. Our four studies suggest that Sequential Information Bottleneck(sIB), a new unsupervised technique, can be adopted to predict the outcome and its ability to detect the target status is superior to the traditional LDA in the study. ^ From our results we can see that the best test probability-HMSS for predicting CVD, stroke,CAD and psoriasis through sIB is 0.59406, 0.641815, 0.645315 and 0.678658, respectively. In terms of group prediction accuracy, the highest test accuracy of sIB for diagnosing a normal status among controls can reach 0.708999, 0.863216, 0.639918 and 0.850275 respectively in the four studies if the test accuracy among cases is required to be not less than 0.4. On the other hand, the highest test accuracy of sIB for diagnosing a disease among cases can reach 0.748644, 0.789916, 0.705701 and 0.749436 respectively in the four studies if the test accuracy among controls is required to be at least 0.4. ^ A further genome-wide association study through Chi square test shows that there are no significant SNPs detected at the cut-off level 9.09451E-08 in the Framingham heart study of CVD. Study results in WTCCC can only detect two significant SNPs that are associated with CAD. In the genome-wide study of psoriasis most of top 20 SNP markers with impressive classification accuracy are also significantly associated with the disease through chi-square test at the cut-off value 1.11E-07. ^ Although our classification methods can achieve high accuracy in the study, complete descriptions of those classification results(95% confidence interval or statistical test of differences) require more cost-effective methods or efficient computing system, both of which can't be accomplished currently in our genome-wide study. We should also note that the purpose of this study is to identify subsets of SNPs with high prediction ability and those SNPs with good discriminant power are not necessary to be causal markers for the disease.^

Characterization of fecal contamination targeting 16S rRNA bacteroides molecular markers in the Santa Cruz River, Arizona

Understanding the origins, transport and fate of contamination is essential to effective management of water resources and public health. Individuals and organizations with management responsibilities need to understand the risks to ecosystems and to humans from contact with contamination. Managers also need to understand how key contaminants vary over time and space in order to design and prioritize mitigation strategies. Tumacacori National Historic Park (NHP) is responsible for management of its water resources for the benefit of the park and for the health of its visitors. The existence of microbial contaminants in the park poses risks that must be considered in park planning and operations. The water quality laboratory at the Maricopa Agricultural Center (in collaboration with stakeholder groups and individuals located in the ADEQ-targeted watersheds) identified biological changes in surface water quality in impaired reaches rivers to determine the sources of Escherichia coli (E. coli); bacteria utilizing innovative water quality microbial/bacterial source tracking methods. The end goal was to support targeted watershed groups and ADEQ towards E. coli reductions. In the field monitoring was conducted by the selected targeted watershed groups in conjunction with The University of Arizona Maricopa Agricultural Center Water Quality Laboratory. This consisted of collecting samples for Bacteroides testing from multiple locations on select impaired reaches, to determine contamination resulting from cattle, human recreation, and other contributions. Such testing was performed in conjunction with high flow and base flow conditions in order to accurately portray water quality conditions and variations. Microbial monitoring was conducted by The University of Arizona Water Quality Laboratory at the Maricopa Agricultural Center using genetic typing to differentiate among two categories of Bacteroides: human and all (total). Testing used microbial detection methodologies and molecular source tracking techniques.^

The identification and regulation of a novel interaction occurring between $\beta$-catenin and the actin -bundling protein fascin

Catenins were first characterized as linking the cytoplasmic domains of cadherin cell-cell adhesion molecules to the cortical actin cytoskeleton. In addition to their essential role in modulating cadherin adhesion, catenins have more recently been indicated to participate in cell and developmental signaling pathways. $\beta$-catenin, for example, associates directly with receptor tyrosine kinases and transcription factors such as LEF-1/TCF, and tranduces developmental signals within the Wnt pathway. $\beta$-catenin also appear to a role in regulating cell proliferation via its interaction with the tumor supressor protein APC. I have employed the yeast two-hybrid method to reveal that fascin, a bundler of actin filaments, binds to $\beta$-catenin's central Armadillo-repeat domain. The $\beta$-catenin-fascin interaction exists in cell lines as well as in animal brain tissues as revealed by immunoprecipitation analysis, and substantiated in vitro with purified proteins. Fascin additionally binds to plakoglobin, which contains a more divergent Armadillo-repeat domain. Fascin and E-cadherin utilize a similar binding-site within $\beta$-catenin, such that they form mutually exclusive complexes with $\beta$-catenin. Fascin and $\beta$-catenin co-localize at cell-cell borders and dynamic cell leading edges of epithelial and endothelial cells. Total immunoprecipitable b-catein has several isoforms, only the hyperphosphorylated isoform 1 associated with fascin. An increased $\beta$-catenin-fascin interaction was observed in HGF stimulated cells, and in Xenopus embryos injected with src kinase RNAs. The increased $\beta$-catenin association with fascin is correlated with increased levels of $\beta$-catenin phosphorylation. $\beta$-catenin, but not fascin, can be readily phosphorylated on tyrosine in vivo following src injection of embryos, or in vitro following v-src addition to purified protein components. These observations suggest a role of $\beta$-catenin phosphorylation in regulating its interaction with fascin, and src kinase may be an important regulator of the $\beta$-catenin-fascin association in vivo. The $\beta$-catenin-fascin interaction represents a novel catenin complex, that may conceivably regulate actin cytoskeletal structures, cell adhesion, and cellular motility, perhaps in a coordinate manner with its functions in cadherin and APC complexes. ^

Handmade Task Tracking Applied to Cognitive Rehabilitation

This article presents research focused on tracking manual tasks that are applied in cognitive rehabilitation so as to analyze the movements of patients who suffer from Apraxia and Action Disorganization Syndrome (AADS). This kind of patients find executing Activities of Daily Living (ADL) too difficult due to the loss of memory and capacity to carry out sequential tasks or the impossibility of associating different objects with their functions. This contribution is developed from the work of Universidad Polit��cnica de Madrid and Technical University of Munich in collaboration with The University of Birmingham. The KinectTM for Windows�� device is used for this purpose. The data collected is compared to an ultrasonic motion capture system. The results indicate a moderate to strong correlation between signals. They also verify that KinectTM is very suitable and inexpensive. Moreover, it turns out to be a motion-capture system quite easy to implement for kinematics analysis in ADL.

Algoritmos para mineria de datos con redes de neuronas

Este trabajo propone una serie de algoritmos con el objetivo de extraer informaci��n de conjuntos de datos con redes de neuronas. Se estudian dichos algoritmos con redes de neuronas Enhenced Neural Networks (ENN), debido a que esta arquitectura tiene algunas ventajas cuando se aproximan funciones mediante redes neuronales. En la red ENN los pesos de la matriz principal vari��n con cada patr��n, por lo que se comete un error menor en la aproximaci��n. Las redes de neuronas ENN re��nen la informaci��n en los pesos de su red auxiliar, se propone un m��todo para obtener informaci��n de la red a trav��s de dichos pesos en formas de reglas y asignando un factor de certeza de dichas reglas. La red ENN obtiene un error cuadr��tico medio menor que el error te��rico de una aproximaci��n matem��tica por ejemplo mediante polinomios de Taylor. Se muestra como una red ENN, entrenada a partir un conjunto de patrones obtenido de una funci��n de variables reales, sus pesos asociados tienen unas relaciones similares a las que se veri_can con las variables independientes con dicha funci��n de variables reales. Las redes de neuronas ENN aproximan polinomios, se extrae conocimiento de un conjunto de datos de forma similar a la regresi��n estad��stica, resolviendo de forma m��s adecuada el problema de multicolionalidad en caso de existir. Las relaciones a partir de los pesos asociados de la matriz de la red auxiliar se obtienen similares a los coeficientes de una regresi��n para el mismo conjunto num��rico. Una red ENN entrenada a partir de un conjunto de datos de una funci��n boolena extrae el conocimiento a partir de los pesos asociados, y la influencia de las variables de la regla l��gica de la funci��n booleana, queda reejada en esos pesos asociados a la red auxiliar de la red ENN. Se plantea una red de base radial (RBF) para la clasificaci��n y predicci��n en problemas forestales y agr��colas, obteniendo mejores resultados que con el modelo de regresi��n y otros m��todos. Los resultados con una red RBF mejoran al m��todo de regresi��n si existe colinealidad entre los datos que se dispone y no son muy numerosos. Tambi��n se detecta que variables tienen m��s importancia en virtud de la variable pron��stico. Obteniendo el error cuadr��tico medio con redes RBF menor que con otros m��todos, en particular que con el modelo de regresi��n. Abstract A series of algorithms is proposed in this study aiming at the goal of producing information about data groups with a neural network. These algorithms are studied with Enheced Neural Networks (ENN), owing to the fact that this structure shows sever advantages when the functions are approximated by neural networks. Main matrix weights in th ENN vary on each pattern; so, a smaller error is produced when approximating. The neural network ENN joins the weight information contained in their auxiliary network. Thus, a method to obtain information on the network through those weights is proposed by means of rules adding a certainty factor. The net ENN obtains a mean squared error smaller than the theorical one emerging from a mathematical aproximation such as, for example, by means of Taylor's polynomials. This study also shows how in a neural network ENN trained from a set of patterns obtained through a function of real variables, its associated weights have relationships similar to those ones tested by means of the independent variables connected with such functions of real variables. The neural network ENN approximates polynomials through it information about a set of data may be obtained in a similar way than through statistical regression, solving in this way possible problems of multicollinearity in a more suitable way. Relationships emerging from the associated weights in the auxiliary network matrix obtained are similar to the coeficients corresponding to a regression for the same numerical set. A net ENN trained from a boolean function data set obtains its information from its associated weights. The inuence of the variables of the boolean function logical rule are reected on those weights associated to the net auxiliar of the ENN. A radial basis neural networks (RBF) for the classification and prediction of forest and agricultural problems is proposed. This scheme obtains better results than the ones obtained by means of regression and other methods. The outputs with a net RBF better the regression method if the collineality with the available data and their amount is not very large. Detection of which variables are more important basing on the forecast variable can also be achieved, obtaining a mean squared error smaller that the ones obtained through other methods, in special the one produced by the regression pattern.

Implementaci��n de una arquitectura de componentes para un sistema de apoyo a la toma de decisiones en Atenci��n Primaria

Este Proyecto Fin de Grado tiene como objetivo fundamental el perfeccionamiento y puesta en explotaci��n de un sistema de ayuda a la decisi��n que eval��a el desarrollo del lenguaje en ni��os de 0 a 6 a��os de edad. Este sistema est�� formado fundamentalmente por una aplicaci��n dise��ada y construida mediante una arquitectura de componentes de software modular y reutilizable. La aplicaci��n ser�� usada por los pediatras para realizar evaluaciones del desarrollo del lenguaje infantil y adem��s por los neuropediatras, logopedas y miembros de equipos de Atenci��n Temprana para consultar las evaluaciones y validar las decisiones propuestas por el sistema. El sistema es accesible v��a web y almacena toda la informaci��n que maneja en una base de datos. Asimismo, el sistema se apoya en un modelo conceptual u ontolog��a desarrollado previamente para inferir las decisiones adecuadas para las evaluaciones del lenguaje. El sistema incorpora las funciones de gesti��n de los usuarios del mismo. ABSTRACT This Grade End Project has as fundamental objective the improvement and deployment of a decision support system for evaluating children language development from 0 to 6 years of age. This system is mainly formed by an application designed and built using a modular and reusable software component architecture. The application will be used by pediatricians for evaluating children��s speech development and also by neuro-pediatricians, speech therapists and early childhood intervention team members, for consulting previous evaluations and for validating system��s proposed decision. The system is web based and stores its information in a database. Likewise, the system is supported by a conceptual model or ontology previously developed to infer the appropriate decision for language evaluation. The system also includes user management functions.

Clustering basado en redes bayesianas con predictoras continuas: aplicaciones en neurociencia

Desentra��ar el funcionamiento del cerebro es uno de los principales desaf��os a los que se enfrenta la ciencia actual. Un ��rea de estudio que ha despertado muchas expectativas e inter��s es el an��lisis de la estructura cortical desde el punto de vista morfol��gico, de manera que se cree una simulaci��n del cerebro a nivel molecular. Con ello se espera poder profundizar en el estudio de numerosas enfermedades neurol��gicas y patol��gicas. Con el desarrollo de este proyecto se persigue el estudio del soma y de las espinas desde el punto de vista de la neuromorfolog��a te��rica. Es com��n en el estado del arte que en el an��lisis de las caracter��sticas morfol��gicas de una neurona en tres dimensiones el soma sea ignorado o, en el mejor de los casos, que sea sustituido por una simple esfera. De hecho, el concepto de soma resulta abstracto porque no se dispone de una dfinici��n estricta y robusta que especifique exactamente donde finaliza y comienzan las dendritas. En este proyecto se alcanza por primera vez una definici��n matem��tica de soma para determinar qu�� es el soma. Con el fin de simular somas se ahonda en los atributos utilizados en el estado del arte. Estas propiedades, de ��ndole gen��rica, no especifican una morfolog��a ��nica. Es por ello que se propone un m��todo que agrupe propiedades locales y globales de la morfolog��a. En disposici��n de las caracter��sticas se procede con la categorizaci��n del cuerpo celular en distintas clases a partir de un nuevo subtipo de red bayesiana din��mica adaptada al espacio. Con ello se discute la existencia de distintas clases de somas y se descubren las diferencias entre los somas piramidales de distintas capas del cerebro. A partir del modelo matem��tico se simulan por primera vez somas virtuales. Algunas morfolog��as de espinas han sido atribuidas a ciertos comportamientos cognitivos. Por ello resulta de inter��s dictaminar las clases existentes y relacionarlas con funciones de la actividad cerebral. La clasificaci��n m��s extendida (Peters y Kaiserman-Abramof, 1970) presenta una definici��n ambigua y subjetiva dependiente de la interpretaci��n de cada individuo y por tanto discutible. Este estudio se sustenta en un conjunto de descriptores extra��dos mediante una t��cnica de an��lisis topol��gico local para representaciones 3D. Sobre estos datos se trata de alcanzar el conjunto de clases m��s adecuado en el que agrupar las espinas as�� como de describir cada grupo mediante reglas un��vocas. A partir de los resultados, se discute la existencia de un continuo de espinas y las propiedades que caracterizan a cada subtipo de espina. ---ABSTRACT---Unravel how the brain works is one of the main challenges faced by current science. A field of study which has aroused great expectations and interest is the analysis of the cortical structure from a morphological point of view, so that a molecular level simulation of the brain is achieved. This is expected to deepen the study of many neurological and pathological diseases. This project seeks the study of the soma and spines from the theoretical neuromorphology point of view. In the state of the art it is common that when it comes to analyze the morphological characteristics of a three dimension neuron the soma is ignored or, in the best case, it is replaced by a simple sphere. In fact, the concept of soma is abstract because there is not a robust and strict definition on exactly where it ends and dendrites begin. In this project a mathematical definition is reached for the first time to determine what a soma is. With the aim to simulate somas the atributes applied in the state of the art are studied. These properties, generic in nature, do not specify a unique morphology. It is why it was proposed a method to group local and global morphology properties. In arrangement of the characteristics it was proceed with the categorization of the celular body into diferent classes by using a new subtype of dynamic Bayesian network adapted to space. From the result the existance of different classes of somas and diferences among pyramidal somas from distinct brain layers are discovered. From the mathematical model virtual somas were simulated for the first time. Some morphologies of spines have been attributed to certain cognitive behaviours. For this reason it is interesting to rule the existent classes and to relate them with their functions in the brain activity. The most extended classification (Peters y Kaiserman-Abramof, 1970) presents an ambiguous and subjective definition that relies on the interpretation of each individual and consequently it is arguable. This study was based on the set of descriptors extracted from a local topological analysis technique for 3D representations. On these data it was tried to reach the most suitable set of classes to group the spines as well as to describe each cluster by unambiguous rules. From these results, the existance of a continuum of spines and the properties that characterize each spine subtype were discussed .

Towards workflow ecosystems through standard representations

Workflows are increasingly used to manage and share scientific computations and methods. Workflow tools can be used to design, validate, execute and visualize scientific workflows and their execution results. Other tools manage workflow libraries or mine their contents. There has been a lot of recent work on workflow system integration as well as common workflow interlinguas, but the interoperability among workflow systems remains a challenge. Ideally, these tools would form a workflow ecosystem such that it should be possible to create a workflow with a tool, execute it with another, visualize it with another, and use yet another tool to mine a repository of such workflows or their executions. In this paper, we describe our approach to create a workflow ecosystem through the use of standard models for provenance (OPM and W3C PROV) and extensions (P-PLAN and OPMW) to represent workflows. The ecosystem integrates different workflow tools with diverse functions (workflow generation, execution, browsing, mining, and visualization) created by a variety of research groups. This is, to our knowledge, the first time that such a variety of workflow systems and functions are integrated.

Color uniformity in spotligths - visual perception and system design

La iluminaci��n con diodos emisores de luz (LED) est�� reemplazando cada vez en mayor medida a las fuentes de luz tradicionales. La iluminaci��n LED ofrece ventajas en eficiencia, consumo de energ��a, dise��o, tama��o y calidad de la luz. Durante m��s de 50 a��os, los investigadores han estado trabajando en mejoras LED. Su principal relevancia para la iluminaci��n est�� aumentando r��pidamente. Esta tesis se centra en un campo de aplicaci��n importante, como son los focos. Se utilizan para enfocar la luz en ��reas definidas, en objetos sobresalientes en condiciones profesionales. Esta iluminaci��n de alto rendimiento requiere una calidad de luz definida, que incluya temperaturas ajustables de color correlacionadas (CCT), de alto ��ndice de reproducci��n crom��tica (CRI), altas eficiencias, y colores vivos y brillantes. En el paquete LED varios chips de diferentes colores (rojo, azul, f��sforo convertido) se combinan para cumplir con la distribuci��n de energ��a espectral con alto CRI. Para colimar la luz en los puntos concretos deseados con un ��ngulo de emisi��n determinado, se utilizan blancos sintonizables y diversos colores de luz y ��pticas secundarias. La combinaci��n de una fuente LED de varios colores con elementos ��pticos puede causar falta de homogeneidad crom��tica en la distribuci��n espacial y angular de la luz, que debe resolverse en el dise��o ��ptico. Sin embargo, no hay necesidad de uniformidad perfecta en el punto de luz debido al umbral en la percepci��n visual del ojo humano. Por lo tanto, se requiere una descripci��n matem��tica del nivel de uniformidad del color con respecto a la percepci��n visual. Esta tesis est�� organizada en siete cap��tulos. Despu��s de un cap��tulo inicial que presenta la motivaci��n que ha guiado la investigaci��n de esta tesis, en el cap��tulo 2 se presentan los fundamentos cient��ficos de la uniformidad del color en luces concentradas, como son: el espacio de color aplicado CIELAB, la percepci��n visual del color, los fundamentos de dise��o de focos respecto a los motores de luz y ��pticas no formadoras de im��genes, y los ��ltimos avances en la evaluaci��n de la uniformidad del color en el campo de los focos. El cap��tulo 3 desarrolla diferentes m��todos para la descripci��n matem��tica de la distribuci��n espacial del color en un ��rea definida, como son la diferencia de color m��xima, la desviaci��n media del color, el gradiente de la distribuci��n espacial de color, as�� como la suavidad radial y axial. Cada funci��n se refiere a los diferentes factores que influyen en la visi��n, los cuales necesitan un tratamiento distinto que el de los datos que se tendr��n en cuenta, adem��s de funciones de ponderaci��n que pre- y post-procesan los datos simulados o medidos para la reducci��n del ruido, la luminancia de corte, la aplicaci��n de la ponderaci��n de luminancia, la funci��n de sensibilidad de contraste, y la funci��n de distribuci��n acumulativa. En el cap��tulo 4, se obtiene la funci��n de m��rito Usl para la estimaci��n de la uniformidad del color percibida en focos. Se bas�� en los resultados de dos conjuntos de experimentos con factor humano realizados para evaluar la percepci��n visual de los sujetos de los patrones de focos t��picos. El primer experimento con factor humano dio lugar al orden de importancia percibida de los focos. El orden de rango percibido se utiliz�� para correlacionar las descripciones matem��ticas de las funciones b��sicas y la funci��n ponderada sobre la distribuci��n espacial del color, que condujo a la funci��n Usl. El segundo experimento con factor humano prob�� la percepci��n de los focos bajo condiciones ambientales diversas, con el objetivo de proporcionar una escala absoluta para Usl, para poder as�� sustituir la opini��n subjetiva personal de los individuos por una funci��n de m��rito estandarizada. La validaci��n de la funci��n Usl se presenta en relaci��n con el alcance de la aplicaci��n y condiciones, as�� como las limitaciones y restricciones que se realizan en el cap��tulo 5. Se compararon los datos medidos y simulados de varios sistemas ��pticos. Se discuten los campos de aplicaci��n , as�� como validaciones y restricciones de la funci��n. El cap��tulo 6 presenta el dise��o del sistema de focos y su optimizaci��n. Una evaluaci��n muestra el an��lisis de sistemas basados en el reflector y la lente TIR. Los sistemas ��pticos simulados se comparan en la uniformidad del color Usl, sensibilidad a las sombras coloreadas, eficiencia e intensidad luminosa m��xima. Se ha comprobado que no hay un sistema ��nico que obtenga los mejores resultados en todas las categor��as, y que una excelente uniformidad de color se pudo alcanzar por la conjunci��n de dos sistemas diferentes. Finalmente, el cap��tulo 7 presenta el resumen de esta tesis y la perspectiva para investigar otros aspectos. ABSTRACT Illumination with light-emitting diodes (LED) is more and more replacing traditional light sources. They provide advantages in efficiency, energy consumption, design, size and light quality. For more than 50 years, researchers have been working on LED improvements. Their main relevance for illumination is rapidly increasing. This thesis is focused on one important field of application which are spotlights. They are used to focus light on defined areas, outstanding objects in professional conditions. This high performance illumination required a defined light quality including tunable correlated color temperatures (CCT), high color rendering index (CRI), high efficiencies and bright, vivid colors. Several differently colored chips (red, blue, phosphor converted) in the LED package are combined to meet spectral power distribution with high CRI, tunable white and several light colors and secondary optics are used to collimate the light into the desired narrow spots with defined angle of emission. The combination of multi-color LED source and optical elements may cause chromatic inhomogeneities in spatial and angular light distribution which needs to solved at the optical design. However, there is no need for perfect uniformity in the spot light due to threshold in visual perception of human eye. Therefore, a mathematical description of color uniformity level with regard to visual perception is required. This thesis is organized seven seven chapters. After an initial one presenting the motivation that has guided the research of this thesis, Chapter 2 introduces the scientific basics of color uniformity in spot lights including: the applied color space CIELAB, the visual color perception, the spotlight design fundamentals with regards to light engines and nonimaging optics, and the state of the art for the evaluation of color uniformity in the far field of spotlights. Chapter 3 develops different methods for mathematical description of spatial color distribution in a defined area, which are the maximum color difference, the average color deviation, the gradient of spatial color distribution as well as the radial and axial smoothness. Each function refers to different visual influencing factors, and they need different handling of data be taken into account, along with weighting functions which pre- and post-process the simulated or measured data for noise reduction, luminance cutoff, the implementation of luminance weighting, contrast sensitivity function, and cumulative distribution function. In chapter 4, the merit function Usl for the estimation of the perceived color uniformity in spotlights is derived. It was based on the results of two sets of human factor experiments performed to evaluate the visual perception of typical spotlight patterns by subjects. The first human factor experiment resulted in the perceived rank order of the spotlights. The perceived rank order was used to correlate the mathematical descriptions of basic functions and weighted function concerning the spatial color distribution, which lead to the Usl function. The second human factor experiment tested the perception of spotlights under varied environmental conditions, with to objective to provide an absolute scale for Usl, so the subjective personal opinion of individuals could be replaced by a standardized merit function. The validation of the Usl function is presented concerning the application range and conditions as well as limitations and restrictions in carried out in chapter 5. Measured and simulated data of various optical several systems were compared. Fields of applications are discussed as well as validations and restrictions of the function. Chapter 6 presents spotlight system design and their optimization. An evaluation shows the analysis of reflector-based and TIR lens systems. The simulated optical systems are compared in color uniformity Usl , sensitivity to colored shadows, efficiency, and peak luminous intensity. It has been found that no single system which performed best in all categories, and that excellent color uniformity could be reached by two different system assemblies. Finally, chapter 7 summarizes the conclusions of the present thesis and an outlook for further investigation topics.

Participaci��n Directa y Aprendizaje de los Trabajadores en Mejoras Tecnol��gicas a Empresas Bajo Gesti��n Colectiva. Aplicaci��n en Industrias Metal��rgicas de Venezuela y Argentina

La industria metal��rgica estatal venezolana ha vivido, desde sus inicios, procesos c��clicos de cambios y ajustes tecnol��gicos. Estos procesos no han sido objeto de sistematizaci��n que asegure el aprendizaje y apropiaci��n del conocimiento. Este hecho, a��n hoy, ha obstaculizado los procesos de apropiaci��n y mejora de las tecnolog��as asociadas al sector. A partir del acompa��amiento a iniciativas de participaci��n de grupos de inter��s surgidos del seno de los trabajadores, se plante�� esta investigaci��n que tuvo como prop��sito la determinaci��n de condiciones y relaciones para su participaci��n directa en los procesos de mejora de las tecnolog��as existentes y el fortalecimiento del aprendizaje asociado. Se consideraron dos ��mbitos Latinoamericanos donde hay manifestaci��n de gesti��n colectiva y participaci��n: Venezuela y Argentina. En el caso venezolano, el abordaje se realiz�� bajo la Investigaci��n Acci��n Participativa (IAP), desarrollando la ���investigaci��n pr��xima���, como estrategia de acompa��amiento, mediante ���talleres de formaci��n-investigaci��n��� y la sistematizaci��n de experiencias considerando la perspectiva y necesidades de los actores. En el caso argentino, el abordaje se realiz�� mediante visitas, entrevistas, reuniones y encuentros. Los talleres realizados en Venezuela, en un contexto de di��logo de saberes, facilitaron el surgimiento de herramientas pr��cticas para la sistematizaci��n de su propia experiencia (���Preguntas generadoras���, ���Mi historia con la tecnolog��a���, ���Bit��cora de aprendizaje���). El intercambio con los pares argentinos ha generado una red que plantea la posibilidad de construcci��n y nucleaci��n conjunta de saberes y experiencia, tanto para los trabajadores como para los investigadores. Los casos estudiados referidos a las empresas recuperadas por los trabajadores (ERTs) argentinos evidencian un proceso de participaci��n marcada por su autonom��a en la gesti��n de la empresa, dadas las circunstancias que los llev�� a asumirla para conservar sus puestos de trabajo. De estos casos emergieron categor��as asociadas con elementos de gesti��n de un proceso t��cnico���tecnol��gico, como la participaci��n en la planificaci��n, concepci��n o dise��o de la mejora. La participaci��n en general est�� asociada al hecho asambleario, vinculado a las pr��cticas de toma de decisiones autogestionarias como expresi��n de una alta participaci��n. La Asamblea, como m��xima instancia de participaci��n, y el Consejo de Administraci��n son las formas de participaci��n prevalecientes. En cuanto al aprendizaje, los trabajadores de las ERTs argentinas aportaron categor��as de gran significaci��n a los procesos de socializaci��n del conocimiento: conocimiento colectivo y cooperaci��n del conocimiento, rescate de los saberes y formaci��n de trabajadores que tomen el relevo. Las categor��as surgidas de las ERTs argentinas, los referentes te��ricos y el inter��s de los trabajadores venezolanos fueron la base para la valoraci��n tanto de su grado de participaci��n en las mejoras a procesos tecnol��gicos emprendidas, como del aprendizaje asociado. ��sta valoraci��n se realiz�� bajo una aproximaci��n borrosa dado el car��cter ambiguo de estas categor��as que fueron trabajadas como conjuntos que se relacionan, m��s que como variables. Se encontr�� que la participaci��n, se configura como un sub-conjunto del aprendizaje para contribuir a su fortalecimiento. Las condiciones y relaciones para fortalecer la participaci��n en los asuntos tecnol��gicos surgieron a partir de la sistematizaci��n y s��ntesis de ambas experiencias (Venezuela y Argentina) conjugando una estructura que contempla la formaci��n para la nucleaci��n de colectivos de saberes (proyectos de mejora o innovaciones), las redes por afinidad, la sistematizaci��n de su propia experiencia t��cnica y los enlaces institucionales. Estos resultados dan cuenta de la integraci��n de los intereses de las partes (trabajadores, investigadores, instituciones), mediante las estrategias de encuentro, de sistematizaci��n de los propios m��todos y de conformaci��n de los ���colectivos de saberes���, la red de IAP en la industria (IAP Industrial) considerando la ���deriva de la investigaci��n���, bajo discursos pr��ctico���te��ricos propios, como posibilidad de posicionamiento de su participaci��n en los asuntos tecnol��gicos de sus respectivas organizaciones, abriendo una oportunidad de ampliaci��n de la experiencia en otros ��mbitos y sectores. ABSTRACT Venezuelan's state owned steel industry has experienced since its earliest years, cycles of change and technological adjustments. These processes have not been systematized to ensure learning and knowledge in those organizations. This fact, even today, has hindered the processes of appropriation and improving the technologies associated with the sector. In order to support initiatives involving metalworker interest groups, this research was aimed at determining conditions and relations for their direct participation in process improvements to existing technologies and strengthening the associated learning. Two Latin American countries, Venezuela and Argentina, were considered on the base of their collective management and participation experiences. The Venezuelan approach was carried out under the Participatory Action Research (PAR) strategy, through the ���proximal research��� as support strategy, by means of ���workshops���research��� and systematization of experiences considering the perspective and needs of actors. Workshops were carried out in metallurgical enterprises from steel and aluminum at Guayana, Venezuela and its affiliates in the Central region. Those industries have been promoted collective management. The Argentine approach was carried out through visits, interviews, meetings and gatherings. The workshops held in Venezuela, in a dialogue of knowledge context, facilitated the emergence of tools for the systematization of their own experience (���generating questions���, ���My history with technology���, ���Learning Log���). The relation with Argentine peers has generated a network that creates opportunities of knowledge and experience construction and its nucleation for both, workers and researchers. The cases studied relating to Argentine workers��� recuperated enterprises show a participatory process marked by autonomy in the management of the factory, given the circumstances that led them to take it in order to maintain their jobs. From these cases emerged categories associated with management aspects about technical-technology process, such as participation in planning, design or implementation of the improvement. Participation, in general, is associated with assemblies, joined to the practices of self-management decision-making as an expression of a high participation. The Cooperative General Assembly, as the highest instance of participation, and the Board of Directors are the prevalent forms of participation. In relation to learning, Argentine workers��� recuperated enterprises provided categories of great significance to the process of socialization of knowledge: collective knowledge and knowledge cooperation, recovery of knowledge and training workers for replacement. Based on categories arising from the Argentine experience, theoretical framework and the interest of the Venezuelan workers the assessment of both, their degree of participation on technical improvements and the associated technological learning were made considering a fuzzy approach, given the ambiguous nature of these categories that were worked as sets rather than variables. It was found that participation is configured as a subset of learning to contribute to its strengthening. The conditions and relations to strengthen participation in technology issues emerged from the systematization and synthesis of both experiences (Venezuela and Argentina) combining a structure which provides training for the nucleation of collectives of knowledge (improvement projects or innovations), affinity networks, systematization of their own expertise and institutional links. These results show the integration of the interests of stakeholders (workers, researchers, institutions) through strategies like meetings, systematization of their own methods, forming ���collectives of technological knowledge��� and a participative action research network in this industry (Industrial PAR) considering the ���research drift���, under their own practical-theoretical discourses positioned as a possibility of their participation in technological activities in their respective organizations, opening an opportunity for scaling to other areas and sectors.

Metodolog��a para la optimizaci��n y an��lisis de la respuesta de medios e infraestructuras en el sistema aeroportuario en operaciones invernales mediante modelos basados en algor��tmos gen��ticos

En este estudio, englobado dentro del campo de la investigaci��n operacional en aeropuertos, se considera el problema de la optimizaci��n de la secuencia de descontaminaci��n de nieve de los tramos que componen el ��rea de maniobras de un aeropuerto, denominado RM-AM. Este problema se enfrenta a la optimizaci��n de recursos limitados para retirar la nieve de las calles de rodadura y pistas, dej��ndolas en un estado aceptable para la operaci��n de aeronaves. El campo de vuelos se divide en subconjuntos de tramos significativos para la operaci��n y se establecen tiempos objetivo de apertura al tr��fico de aeronaves. Se desarrollan varios algoritmos matem��ticos en los que se proponen distintas funciones objetivo, como son la hora de finalizaci��n del proceso, la suma de las horas de finalizaci��n de cada tramo, o el retraso entre la hora estimada y la hora de finalizaci��n. Durante este proceso, se van introduciendo restricciones operativas relativas al cumplimiento de objetivos operativos parciales aplicados a las zonas de especial inter��s, o relativas a la operaci��n de los equipos de descontaminaci��n. El problema se resuelve mediante optimizaci��n basada en programaci��n lineal. Los resultados de las pruebas computacionales se hacen sobre cinco modelos de ��rea de maniobras en los que va creciendo la complejidad y el tama��o. Se comparan las prestaciones de los distintos algoritmos. Una vez definido el modelo matem��tico para la optiamizaci��n, se propone una metodolog��a estructurada para abordar dicho problema para cualquier ��rea de manobras. Se define una estrategia en la operaci��n. Se acomete el ��rea de maniobras por zonas, con la condici��n de que los subconjuntos de tramos significativos queden englobados dentro de una sola de estas zonas. El problema se resuelve mediante un proceso iterativo de optimizaci��n aplicado sucesivamente a las zonas que componen el ��rea de maniobras durante cada iteraci��n. Se analiza la repercusi��n de los resultados en los procesos DMAN, AMAN y TP, para la integraci��n de los resultados en el c��lculo de TSAT y EBIT. El m��todo se particulariza para el caso del ��rea de maniobras del Aeropuerto Adolfo Su��rez Madrid Barajas. ABSTRACT This study, which lies within the field of operations research in airports, considers the optimisation of the sequence for clearing snow from stretches of the manoeuvring area of an airport, known as RM-AM. This issue involves the optimisation of limited resources to remove snow from taxiways and runways thereby leaving them in an acceptable condition for operating aircraft. The airfield is divided into subsets of significant stretches for the purpose of operations and target times are established during which these are open to aircraft traffic. The study contains several mathematical models each with different functions, such as the end time of the process, the sum of the end times of each stretch, and gap between the estimated and the real end times. During this process, we introduce different operating restrictions on partial fulfilment of the operational targets as applied to zones of special interest, or relating to the operation of the snow-clearing machines. The problem is solved by optimisation based on linear programming. Computational tests are carried out on five distinct models of the manoeuvring area, which cover increasingly complex situations and larger areas. The different algorithms are then compared to one other. Having defined the mathematical model for the optimisation, we then set out a structured methodology to deal with any type of manoeuvring area. In other words, we define an operational strategy. The airfield is divided into subsets of significant stretches for the purpose of operations and target times are set at which these are to be open to aircraft traffic. The manoeuvring area is also divided into zones, with the condition that the subsets of significant stretches lie within just one of these zones. The problem is solved by an iterative optimisation process based on linear programming applied successively to the zones that make up the manoeuvring area during each iteration. The impact of the results on DMAN, AMAN and TP processes is analysed for their integration into the calculation of TSAT and EBIT. The method is particularized for the case of the manoeuvring area of Adolfo Suarez Madrid - Barajas Airport.

La cuesti��n de la vivienda social en Brasil: una propuesta de implantaci��n urbana y de producci��n en serie de unidades residenciales unifamiliares para el nordeste brasile��o

La simple lectura de peri��dicos en la prensa o en Internet, o lo ver o o��r de los noticieros en las emisoras de radio o televisi��n, fornecen subsidios ya suficientes para la percepci��n de la amplitud de la cuesti��n de la vivienda social en todo el mundo. Esto trabajo, que ahora se presenta, es el resultado de una investigaci��n cient��fica desarrollada de modo a subsidiar una Tesis de Doctorado a ser presentada en la Universidad Polit��cnica de Madrid. En la investigaci��n cient��fica, se pretendi�� sistematizar lecturas y datos sobre la cuesti��n habitar en todo el mundo, y sobre todo en Brasil, donde se tuvo como foco principal, las poblaciones inseridas en las fajas de renta inferiores a ���300 mensuales, ubicadas en nordeste de Brasil. Bas��ndose en todo eso trabajo de investigaci��n cient��fica, que tanto se preocup�� con los aspectos ergon��micos, sociales, conceptuales, proy��ctales, ambientales, arquitect��nicos y urban��sticos, como tambi��n con los estad��sticos, tecnol��gicos, infraestructurales, econ��micos y comerciales, se propugn�� una metodolog��a para la implantaci��n urbana de asentamientos planeados de viviendas sociales y la producci��n en serie de unidades residenciales unifamiliares. La cuesti��n urbana fue la primera preocupaci��n del cient��fico, tanto en lo que se refiere al planeamiento estrat��gico de ciudades, como los temas que envuelven la espontaneidad, intencionalidad, territorialidad y centralidades de las ocupaciones humanas en la modernidad y postmodernidad. Proyectos de edificios y de conjuntos de viviendas, as�� como planes urbanos, fueron utilizados como estudios de casos de modo a basar los an��lisis presentados en esa tesis. La definici��n de dise��os para la vivienda social, tuvo como premisas, la mejor adecuaci��n posible a las caracter��sticas bioclim��ticas de los diversos sitios elegidos y atender a las necesidades presentadas por los futuros usuarios de los objetos arquitect��nicos construidos. Los partidos arquitect��nicos adoptados intentaron ser coherentes con los valores antropol��gicos y culturales de las poblaciones atendidas con los bienes producidos, y se ajustaren a las capacidades de comprometimiento financiero de las diversas comunidades atendidas con las edificaciones. Pretendi�� a��n, esa tesis de doctorado, hacer una correlaci��n entre las pol��ticas oficiales apuntadas para la vivienda social existentes en Brasil y las encontradas en los pa��ses desarrollados; as�� como los antecedentes hist��ricos de las singulares problem��ticas habitacionales, que tuvieron como cumbre la producci��n de estrategias gerenciales propias. Se aprovecho, tambi��n, mucho de la experiencia norteamericana y europea de industrializaci��n, para ser empleada en la producci��n en serie de unidades habitacionales en nordeste de Brasil, de modo a que esa tecnolog��a de construcci��n tanto pueda ser operada por un sistema fabril formal, cuanto por procesos de autogesti��n y autoconstrucci��n, actualmente adoptados en amplia escala en Brasil. ABSTRACT The simple reading of nowadays newspapers or the facts presented at Internet, or that can been seen on television or heard on a radio, gives the audience enough arguments to support the right perception of the magnitude of housing problem around the world. This paper is the result of a scientific investigation developed to support a Doctoral Thesis, which will be presented in the Universidad Polit��cnica de Madrid. This research aimed at presenting a methodology for serial production of housing designed for planned areas and their integration to urban space. Information that refers to housing problem around the world, including Brazil, was systematized. We selected as target people that live in the Northeast Region of the country and perceive less than ���300 per month as a salary. We analyzed data regarding ergonomic, social, conceptual, environmental and architectural aspects, as well as project and urban information; and also considering statistical, technological, infrastructural, economical and commercial issues. Urban request was the first aspect analyzed. City strategic plan and themes involving aspects such as spontaneity, intentionality, territory and centrality of human occupations in modern and postmodern time were deeply considered. This thesis is also referenced on well known building projects and cities planning. The most adequate constructions considering local weather and poor people architectural necessities programs were pointed out before defining the projects��� sketches. The coherence between plans and anthropologic-cultural values, and also the perfect match to future owners��� financial capacities were also objectives of this work. This study also intended to compare Brazilian���s policies to the ones found in developed countries; and discusses historical facts involved with housing problem, which resulted with management strategies and policies. Some aspects of North American and European industrial experiences were applied to develop serial production of Northeast Brazilian housing. The technology obtained with this methodology intends to be applied in industrial production and also in self-management or self-production procedures, largely used in Brazil.

Evolutionary analyses of hedgehog and Hoxd-10 genes in fish species closely related to the zebrafish

The study of development has relied primarily on the isolation of mutations in genes with specific functions in development and on the comparison of their expression patterns in normal and mutant phenotypes. Comparative evolutionary analyses can complement these approaches. Phylogenetic analyses of Sonic hedgehog (Shh) and Hoxd-10 genes from 18 cyprinid fish species closely related to the zebrafish provide novel insights into the functional constraints acting on Shh. Our results confirm and extend those gained from expression and crystalline structure analyses of this gene. Unexpectedly, exon 1 of Shh is found to be almost invariant even in third codon positions among these morphologically divergent species suggesting that this exon encodes for a functionally important domain of the hedgehog protein. This is surprising because the main functional domain of Shh had been thought to be that encoded by exon 2. Comparisons of Shh and Hoxd-10 gene sequences and of resulting gene trees document higher evolutionary constraints on the former than on the latter. This might be indicative of more general evolutionary patterns in networks of developmental regulatory genes interacting in a hierarchical fashion. The presence of four members of the hedgehog gene family in cyprinid fishes was documented and their homologies to known hedgehog genes in other vertebrates were established.

A complex ligase ribozyme evolved in vitro from a group I ribozyme domain

Like most proteins, complex RNA molecules often are modular objects made up of distinct structural and functional domains. The component domains of a protein can associate in alternative combinations to form molecules with different functions. These observations raise the possibility that complex RNAs also can be assembled from preexisting structural and functional domains. To test this hypothesis, an in vitro evolution procedure was used to isolate a previously undescribed class of complex ligase ribozymes, starting from a pool of 1016 different RNA molecules that contained a constant region derived from a large structural domain that occurs within self-splicing group I ribozymes. Attached to this constant region were three hypervariable regions, totaling 85 nucleotides, that gave rise to the catalytic motif within the evolved catalysts. The ligase ribozymes catalyze formation of a 3���,5���-phosphodiester linkage between adjacent template-bound oligonucleotides, one bearing a 3��� hydroxyl and the other a 5��� triphosphate. Ligation occurs in the context of a Watson���Crick duplex, with a catalytic rate of 0.26 min���1 under optimal conditions. The constant region is essential for catalytic activity and appears to retain the tertiary structure of the group I ribozyme. This work demonstrates that complex RNA molecules, like their protein counterparts, can share common structural domains while exhibiting distinct catalytic functions.

Identification and characterization of a human protein kinase related to budding yeast���Cdc7p

The Cdc7p protein kinase is essential for the G1/S transition and initiation of DNA replication during the cell division cycle in Saccharomyces cerevisiae. Cdc7p appears to be an evolutionarily conserved protein, since a homolog Hsk1 has been isolated from Schizosaccharomyces pombe. Here, we report the isolation of a human cDNA, HsCdc7, whose product is closely related in sequence to Cdc7p and Hsk1. The HsCdc7 cDNA encodes a protein of 574 amino acids with predicted size of 64 kDa. HsCdc7 contains the conserved subdomains common to all protein-serine/threonine kinases and three ���kinase inserts��� that are characteristic of Cdc7p and Hsk1. Immune complexes of HsCdc7 from cell lysates were able to phosphorylate histone H1 in vitro. Indirect immunofluorescence staining demonstrated that HsCdc7 protein was predominantly localized in the nucleus. Although the expression levels of HsCdc7 appeared to be constant throughout the cell cycle, the protein kinase activity of HsCdc7 increased during S phase of the cell cycle at approximately the same time as that of Cdk2. These results, together with the functions of Cdc7p in yeast, suggest that HsCdc7 may phosphorylate critical substrate(s) that regulate the G1/S phase transition and/or DNA replication in mammalian cells.