TEX86H proxy and BIT index of sediment core GeoB9528-3 and reconstructed temperature data from NW Africa surface sediments

Changes in the strength of Atlantic meridional overturning circulation (AMOC) are known to have profound impacts on global climate. Coupled modelling studies have suggested that, on annual to multi-decadal time scales, a slowdown of AMOC causes a deepening of the thermocline in the tropical Atlantic. However, this process has been poorly constrained by sedimentary geochemical records. Here, we reconstruct surface (UK'37 Index) and thermocline (TEX86H) water temperatures from the Guinea Plateau Margin (Eastern tropical Atlantic) over the last two glacial-interglacial cycles (~ 192 kyr). These paleotemperature records show that periods of reduced AMOC, as indicated by the d13 C benthic foraminiferal record from the same core, coincide with a reduction in the near-surface vertical temperature gradient, demonstrating for the first time that AMOC-induced tropical Atlantic thermocline adjustment exists on longer, millennial time scales. Modelling results support the interpretation of the geochemical records and show that thermocline adjustment is particularly pronounced in the eastern tropical Atlantic. Thus, variations in AMOC strength appear to be an important driver of the thermocline structure in the tropical Atlantic from annual to multi-millennial time scales.

Caste, land, and migration : a preliminary analysis of a village survey in an underdeveloped state in India

This paper explores migration from Bihar, one of the most underdeveloped states in India, by paying particular attention to social class (caste) and landholdings. After describing details of individual migrants, we present our preliminary findings on the determinants of migration, based on our field survey of 200 households in four villages in 2011. In terms of social class, Muslims are more likely to migrate, but Scheduled Castes do not show a high propensity to migrate as is stated in some of the existing literature where the underclass is said to be more mobile. In terms of landholdings, the probability that someone will migrate is high among the landless and smaller landholders but it decreases as the size of the landholding increases. However, as the size of the landholding increases still further, a reverse effect of landholding on decisions regarding migration moves in, with the decline in probability becoming less and less. This result confirms a non-linear relationship between landholdings and the decision to migrate. Some further research questions are raised in the paper.

Statistical Calculation of the Main Reliability Functions of GaAs Concentrator III-V Solar Cells

This paper presents some of the results of a method to determine the main reliability functions of concentrator solar cells. High concentrator GaAs single junction solar cells have been tested in an Accelerated Life Test. The method can be directly applied to multi-junction solar cells. The main conclusions of this test carried out show that these solar cells are robust devices with a very low probability of failure caused by degradation during their operation life (more than 30 years). The evaluation of the probability operation function (i.e. the reliability function R(t)) is obtained for two nominal operation conditions of these cells, namely simulated concentration ratios of 700 and 1050 suns. Preliminary determination of the Mean Time to Failure indicates a value much higher than the intended operation life time of the concentrator cells.

Experimental results on multicarrier MIMO HF communications

Achieving reliable communication over HF channels is known to be challenging due to the particularly hostile propagation medium. To address this problem, diversity techniques were shown to be promising. In this paper, we demonstrate through experimental results the benefits of different diversity strategies when applied to multi-input-multi-output (MIMO) multicarrier systems. The performance gains of polarisation, space and frequency diversities are quantified using different measurement campaigns

Heterologous Expression of a Plant Small Heat-Shock Protein Enhances Escherichia Coli Viability under Heat And Cold Stress Ref.: 1

A small heat-shock protein (sHSP) that shows molecular chaperone activity in vitro was recently purified from mature chestnut (Castanea sativa) cotyledons. This protein, renamed here as CsHSP17.5, belongs to cytosolic class I, as revealed by cDNA sequencing and immunoelectron microscopy. Recombinant CsHSP17.5 was overexpressed in Escherichia coli to study its possible function under stress conditions. Upon transfer from 37°C to 50°C, a temperature known to cause cell autolysis, those cells that accumulated CsHSP17.5 showed improved viability compared with control cultures. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of cell lysates suggested that such a protective effect in vivo is due to the ability of recombinant sHSP to maintain soluble cytosolic proteins in their native conformation, with little substrate specificity. To test the recent hypothesis that sHSPs may be involved in protection against cold stress, we also studied the viability of recombinant cells at 4°C. Unlike the major heat-induced chaperone, GroEL/ES, the chestnut sHSP significantly enhanced cell survivability at this temperature. CsHSP17.5 thus represents an example of a HSP capable of protecting cells against both thermal extremes. Consistent with these findings, high-level induction of homologous transcripts was observed in vegetative tissues of chestnut plantlets exposed to either type of thermal stress but not salt stress

Análisis de los factores determinantes de la repetición del proceso de compra en el comercio electrónico entre empresas y consumidores finales. Aplicación al mercado español

Las Tecnologías de la Información y la Comunicación en general e Internet en particular han supuesto una revolución en nuestra forma de comunicarnos, relacionarnos, producir, comprar y vender acortando tiempo y distancias entre proveedores y consumidores. A la paulatina penetración del ordenador, los teléfonos inteligentes y la banda ancha fija y/o móvil ha seguido un mayor uso de estas tecnologías entre ciudadanos y empresas. El comercio electrónico empresa–consumidor (B2C) alcanzó en 2010 en España un volumen de 9.114 millones de euros, con un incremento del 17,4% respecto al dato registrado en 2009. Este crecimiento se ha producido por distintos hechos: un incremento en el porcentaje de internautas hasta el 65,1% en 2010 de los cuales han adquirido productos o servicios a través de la Red un 43,1% –1,6 puntos porcentuales más respecto a 2010–. Por otra parte, el gasto medio por comprador ha ascendido a 831€ en 2010, lo que supone un incremento del 10,9% respecto al año anterior. Si segmentamos a los compradores según por su experiencia anterior de compra podemos encontrar dos categorías: el comprador novel –que adquirió por primera vez productos o servicios en 2010– y el comprador constante –aquel que había adquirido productos o servicios en 2010 y al menos una vez en años anteriores–. El 85,8% de los compradores se pueden considerar como compradores constantes: habían comprado en la Red en 2010, pero también lo habían hecho anteriormente. El comprador novel tiene un perfil sociodemográfico de persona joven de entre 15–24 años, con estudios secundarios, de clase social media y media–baja, estudiante no universitario, residente en poblaciones pequeñas y sigue utilizando fórmulas de pago como el contra–reembolso (23,9%). Su gasto medio anual ascendió en 2010 a 449€. El comprador constante, o comprador que ya había comprado en Internet anteriormente, tiene un perfil demográfico distinto: estudios superiores, clase alta, trabajador y residente en grandes ciudades, con un comportamiento maduro en la compra electrónica dada su mayor experiencia –utiliza con mayor intensidad canales exclusivos en Internet que no disponen de tienda presencial–. Su gasto medio duplica al observado en compradores noveles (con una media de 930€ anuales). Por tanto, los compradores constantes suponen una mayoría de los compradores con un gasto medio que dobla al comprador que ha adoptado el medio recientemente. Por consiguiente es de interés estudiar los factores que predicen que un internauta vuelva a adquirir un producto o servicio en la Red. La respuesta a esta pregunta no se ha revelado sencilla. En España, la mayoría de productos y servicios aún se adquieren de manera presencial, con una baja incidencia de las ventas a distancia como la teletienda, la venta por catálogo o la venta a través de Internet. Para dar respuesta a las preguntas planteadas se ha investigado desde distintos puntos de vista: se comenzará con un estudio descriptivo desde el punto de vista de la demanda que trata de caracterizar la situación del comercio electrónico B2C en España, poniendo el foco en las diferencias entre los compradores constantes y los nuevos compradores. Posteriormente, la investigación de modelos de adopción y continuidad en el uso de las tecnologías y de los factores que inciden en dicha continuidad –con especial interés en el comercio electrónico B2C–, permiten afrontar el problema desde la perspectiva de las ecuaciones estructurales pudiendo también extraer conclusiones de tipo práctico. Este trabajo sigue una estructura clásica de investigación científica: en el capítulo 1 se introduce el tema de investigación, continuando con una descripción del estado de situación del comercio electrónico B2C en España utilizando fuentes oficiales (capítulo 2). Posteriormente se desarrolla el marco teórico y el estado del arte de modelos de adopción y de utilización de las tecnologías (capítulo 3) y de los factores principales que inciden en la adopción y continuidad en el uso de las tecnologías (capítulo 4). El capítulo 5 desarrolla las hipótesis de la investigación y plantea los modelos teóricos. Las técnicas estadísticas a utilizar se describen en el capítulo 6, donde también se analizan los resultados empíricos sobre los modelos desarrollados en el capítulo 5. El capítulo 7 expone las principales conclusiones de la investigación, sus limitaciones y propone nuevas líneas de investigación. La primera parte corresponde al capítulo 1, que introduce la investigación justificándola desde un punto de vista teórico y práctico. También se realiza una breve introducción a la teoría del comportamiento del consumidor desde una perspectiva clásica. Se presentan los principales modelos de adopción y se introducen los modelos de continuidad de utilización que se estudiarán más detalladamente en el capítulo 3. En este capítulo se desarrollan los objetivos principales y los objetivos secundarios, se propone el mapa mental de la investigación y se planifican en un cronograma los principales hitos del trabajo. La segunda parte corresponde a los capítulos dos, tres y cuatro. En el capítulo 2 se describe el comercio electrónico B2C en España utilizando fuentes secundarias. Se aborda un diagnóstico del sector de comercio electrónico y su estado de madurez en España. Posteriormente, se analizan las diferencias entre los compradores constantes, principal interés de este trabajo, frente a los compradores noveles, destacando las diferencias de perfiles y usos. Para los dos segmentos se estudian aspectos como el lugar de acceso a la compra, la frecuencia de compra, los medios de pago utilizados o las actitudes hacia la compra. El capítulo 3 comienza desarrollando los principales conceptos sobre la teoría del comportamiento del consumidor, para continuar estudiando los principales modelos de adopción de tecnología existentes, analizando con especial atención su aplicación en comercio electrónico. Posteriormente se analizan los modelos de continuidad en el uso de tecnologías (Teoría de la Confirmación de Expectativas; Teoría de la Justicia), con especial atención de nuevo a su aplicación en el comercio electrónico. Una vez estudiados los principales modelos de adopción y continuidad en el uso de tecnologías, el capítulo 4 analiza los principales factores que se utilizan en los modelos: calidad, valor, factores basados en la confirmación de expectativas –satisfacción, utilidad percibida– y factores específicos en situaciones especiales –por ejemplo, tras una queja– como pueden ser la justicia, las emociones o la confianza. La tercera parte –que corresponde al capítulo 5– desarrolla el diseño de la investigación y la selección muestral de los modelos. En la primera parte del capítulo se enuncian las hipótesis –que van desde lo general a lo particular, utilizando los factores específicos analizados en el capítulo 4– para su posterior estudio y validación en el capítulo 6 utilizando las técnicas estadísticas apropiadas. A partir de las hipótesis, y de los modelos y factores estudiados en los capítulos 3 y 4, se definen y vertebran dos modelos teóricos originales que den respuesta a los retos de investigación planteados en el capítulo 1. En la segunda parte del capítulo se diseña el trabajo empírico de investigación definiendo los siguientes aspectos: alcance geográfico–temporal, tipología de la investigación, carácter y ambiente de la investigación, fuentes primarias y secundarias utilizadas, técnicas de recolección de datos, instrumentos de medida utilizados y características de la muestra utilizada. Los resultados del trabajo de investigación constituyen la cuarta parte de la investigación y se desarrollan en el capítulo 6, que comienza analizando las técnicas estadísticas basadas en Modelos de Ecuaciones Estructurales. Se plantean dos alternativas, modelos confirmatorios correspondientes a Métodos Basados en Covarianzas (MBC) y modelos predictivos. De forma razonada se eligen las técnicas predictivas dada la naturaleza exploratoria de la investigación planteada. La segunda parte del capítulo 6 desarrolla el análisis de los resultados de los modelos de medida y modelos estructurales construidos con indicadores formativos y reflectivos y definidos en el capítulo 4. Para ello se validan, sucesivamente, los modelos de medida y los modelos estructurales teniendo en cuenta los valores umbrales de los parámetros estadísticos necesarios para la validación. La quinta parte corresponde al capítulo 7, que desarrolla las conclusiones basándose en los resultados del capítulo 6, analizando los resultados desde el punto de vista de las aportaciones teóricas y prácticas, obteniendo conclusiones para la gestión de las empresas. A continuación, se describen las limitaciones de la investigación y se proponen nuevas líneas de estudio sobre distintos temas que han ido surgiendo a lo largo del trabajo. Finalmente, la bibliografía recoge todas las referencias utilizadas a lo largo de este trabajo. Palabras clave: comprador constante, modelos de continuidad de uso, continuidad en el uso de tecnologías, comercio electrónico, B2C, adopción de tecnologías, modelos de adopción tecnológica, TAM, TPB, IDT, UTAUT, ECT, intención de continuidad, satisfacción, confianza percibida, justicia, emociones, confirmación de expectativas, calidad, valor, PLS. ABSTRACT Information and Communication Technologies in general, but more specifically those related to the Internet in particular, have changed the way in which we communicate, relate to one another, produce, and buy and sell products, reducing the time and shortening the distance between suppliers and consumers. The steady breakthrough of computers, Smartphones and landline and/or wireless broadband has been greatly reflected in its large scale use by both individuals and businesses. Business–to–consumer (B2C) e–commerce reached a volume of 9,114 million Euros in Spain in 2010, representing a 17.4% increase with respect to the figure in 2009. This growth is due in part to two different facts: an increase in the percentage of web users to 65.1% en 2010, 43.1% of whom have acquired products or services through the Internet– which constitutes 1.6 percentage points higher than 2010. On the other hand, the average spending by individual buyers rose to 831€ en 2010, constituting a 10.9% increase with respect to the previous year. If we select buyers according to whether or not they have previously made some type of purchase, we can divide them into two categories: the novice buyer–who first made online purchases in 2010– and the experienced buyer: who also made purchases in 2010, but had done so previously as well. The socio–demographic profile of the novice buyer is that of a young person between 15–24 years of age, with secondary studies, middle to lower–middle class, and a non–university educated student who resides in smaller towns and continues to use payment methods such as cash on delivery (23.9%). In 2010, their average purchase grew to 449€. The more experienced buyer, or someone who has previously made purchases online, has a different demographic profile: highly educated, upper class, resident and worker in larger cities, who exercises a mature behavior when making online purchases due to their experience– this type of buyer frequently uses exclusive channels on the Internet that don’t have an actual store. His or her average purchase doubles that of the novice buyer (with an average purchase of 930€ annually.) That said, the experienced buyers constitute the majority of buyers with an average purchase that doubles that of novice buyers. It is therefore of interest to study the factors that help to predict whether or not a web user will buy another product or use another service on the Internet. The answer to this question has proven not to be so simple. In Spain, the majority of goods and services are still bought in person, with a low amount of purchases being made through means such as the Home Shopping Network, through catalogues or Internet sales. To answer the questions that have been posed here, an investigation has been conducted which takes into consideration various viewpoints: it will begin with a descriptive study from the perspective of the supply and demand that characterizes the B2C e–commerce situation in Spain, focusing on the differences between experienced buyers and novice buyers. Subsequently, there will be an investigation concerning the technology acceptance and continuity of use of models as well as the factors that have an effect on their continuity of use –with a special focus on B2C electronic commerce–, which allows for a theoretic approach to the problem from the perspective of the structural equations being able to reach practical conclusions. This investigation follows the classic structure for a scientific investigation: the subject of the investigation is introduced (Chapter 1), then the state of the B2C e–commerce in Spain is described citing official sources of information (Chapter 2), the theoretical framework and state of the art of technology acceptance and continuity models are developed further (Chapter 3) and the main factors that affect their acceptance and continuity (Chapter 4). Chapter 5 explains the hypothesis behind the investigation and poses the theoretical models that will be confirmed or rejected partially or completely. In Chapter 6, the technical statistics that will be used are described briefly as well as an analysis of the empirical results of the models put forth in Chapter 5. Chapter 7 explains the main conclusions of the investigation, its limitations and proposes new projects. First part of the project, chapter 1, introduces the investigation, justifying it from a theoretical and practical point of view. It is also a brief introduction to the theory of consumer behavior from a standard perspective. Technology acceptance models are presented and then continuity and repurchase models are introduced, which are studied more in depth in Chapter 3. In this chapter, both the main and the secondary objectives are developed through a mind map and a timetable which highlights the milestones of the project. The second part of the project corresponds to Chapters Two, Three and Four. Chapter 2 describes the B2C e–commerce in Spain from the perspective of its demand, citing secondary official sources. A diagnosis concerning the e–commerce sector and the status of its maturity in Spain is taken on, as well as the barriers and alternative methods of e–commerce. Subsequently, the differences between experienced buyers, which are of particular interest to this project, and novice buyers are analyzed, highlighting the differences between their profiles and their main transactions. In order to study both groups, aspects such as the place of purchase, frequency with which online purchases are made, payment methods used and the attitudes of the purchasers concerning making online purchases are taken into consideration. Chapter 3 begins by developing the main concepts concerning consumer behavior theory in order to continue the study of the main existing acceptance models (among others, TPB, TAM, IDT, UTAUT and other models derived from them) – paying special attention to their application in e–commerce–. Subsequently, the models of technology reuse are analyzed (CDT, ECT; Theory of Justice), focusing again specifically on their application in e–commerce. Once the main technology acceptance and reuse models have been studied, Chapter 4 analyzes the main factors that are used in these models: quality, value, factors based on the contradiction of expectations/failure to meet expectations– satisfaction, perceived usefulness– and specific factors pertaining to special situations– for example, after receiving a complaint justice, emotions or confidence. The third part– which appears in Chapter 5– develops the plan for the investigation and the sample selection for the models that have been designed. In the first section of the Chapter, the hypothesis is presented– beginning with general ideas and then becoming more specific, using the detailed factors that were analyzed in Chapter 4– for its later study and validation in Chapter 6– as well as the corresponding statistical factors. Based on the hypothesis and the models and factors that were studied in Chapters 3 and 4, two original theoretical models are defined and organized in order to answer the questions posed in Chapter 1. In the second part of the Chapter, the empirical investigation is designed, defining the following aspects: geographic–temporal scope, type of investigation, nature and setting of the investigation, primary and secondary sources used, data gathering methods, instruments according to the extent of their use and characteristics of the sample used. The results of the project constitute the fourth part of the investigation and are developed in Chapter 6, which begins analyzing the statistical techniques that are based on the Models of Structural Equations. Two alternatives are put forth: confirmatory models which correspond to Methods Based on Covariance (MBC) and predictive models– Methods Based on Components–. In a well–reasoned manner, the predictive techniques are chosen given the explorative nature of the investigation. The second part of Chapter 6 explains the results of the analysis of the measurement models and structural models built by the formative and reflective indicators defined in Chapter 4. In order to do so, the measurement models and the structural models are validated one by one, while keeping in mind the threshold values of the necessary statistic parameters for their validation. The fifth part corresponds to Chapter 7 which explains the conclusions of the study, basing them on the results found in Chapter 6 and analyzing them from the perspective of the theoretical and practical contributions, and consequently obtaining conclusions for business management. The limitations of the investigation are then described and new research lines about various topics that came up during the project are proposed. Lastly, all of the references that were used during the project are listed in a final bibliography. Key Words: constant buyer, repurchase models, continuity of use of technology, e–commerce, B2C, technology acceptance, technology acceptance models, TAM, TPB, IDT, UTAUT, ECT, intention of repurchase, satisfaction, perceived trust/confidence, justice, feelings, the contradiction of expectations, quality, value, PLS.

Termination and cost analysis: Complexity and precision issues

The research in this thesis is related to static cost and termination analysis. Cost analysis aims at estimating the amount of resources that a given program consumes during the execution, and termination analysis aims at proving that the execution of a given program will eventually terminate. These analyses are strongly related, indeed cost analysis techniques heavily rely on techniques developed for termination analysis. Precision, scalability, and applicability are essential in static analysis in general. Precision is related to the quality of the inferred results, scalability to the size of programs that can be analyzed, and applicability to the class of programs that can be handled by the analysis (independently from precision and scalability issues). This thesis addresses these aspects in the context of cost and termination analysis, from both practical and theoretical perspectives. For cost analysis, we concentrate on the problem of solving cost relations (a form of recurrence relations) into closed-form upper and lower bounds, which is the heart of most modern cost analyzers, and also where most of the precision and applicability limitations can be found. We develop tools, and their underlying theoretical foundations, for solving cost relations that overcome the limitations of existing approaches, and demonstrate superiority in both precision and applicability. A unique feature of our techniques is the ability to smoothly handle both lower and upper bounds, by reversing the corresponding notions in the underlying theory. For termination analysis, we study the hardness of the problem of deciding termination for a speci�c form of simple loops that arise in the context of cost analysis. This study gives a better understanding of the (theoretical) limits of scalability and applicability for both termination and cost analysis.

Experimental results on multicarrier SIMO HF communications

Achieving reliable communication over HF channels is known to be challenging due to the particularly hostile propagation medium. To address this problem, diversity techniques were shown to be promising. In this paper, we demonstrate through experimental results the benefits of different diversity strategies when applied to multi-input-multi-output (MIMO) multicarrier systems. The performance gains of polarisation, space and frequency diversities are quantified using different measurement campaigns.

An algorithm for graphical computer results in shells

A Finite Element technique to interpolate general data (function values and its derivatives) has been developped. The technique can be considered as a generalized solution of the classical polynomial interpolation, because the condition for the interpolating function to be a polynomial is replaced by a minimizing condition of a given “smoothing” functional. In this way it is possible to find interpolating functions with a given level of continuity according to the class of finite elements used. Examples have been presented in order to assess the accuracy and efficiency of the procedure.

Metodología de análisis estadístico de roturas en redes de distribución de agua

La presente Tesis plantea una metodología de análisis estadístico de roturas de tubería en redes de distribución de agua, que analiza la relación entre las roturas y la presión de agua y que propone la implantación de una gestión de presiones que reduzca el número de roturas que se producen en dichas redes. Las redes de distribución de agua se deterioran y una de sus graves consecuencias es la aparición de roturas frecuentes en sus tuberías. Las roturas llevan asociados elevados costes sociales, económicos y medioambientales y es por ello por lo que las compañías gestoras del agua tratan de reducirlas en la medida de lo posible. Las redes de distribución de agua se pueden dividir en zonas o sectores que facilitan su control y que pueden ser independientes o aislarse mediante válvulas, como ocurre en las redes de países más desarrollados, o pueden estar intercomunicados hidráulicamente. La implantación de una gestión de presiones suele llevarse a cabo a través de las válvulas reductoras de presión (VPR), que se instalan en las cabeceras de estos sectores y que controlan la presión aguas abajo de la misma, aunque varíe su caudal de entrada. Los métodos más conocidos de la gestión de presiones son la reducción de presiones, que es el control más habitual, el mantenimiento de la presión, la prevención y/o alivio de los aumentos repentinos de presión y el establecimiento de un control por alturas. A partir del año 2005 se empezó a reconocer el efecto de la gestión de presiones sobre la disminución de las roturas. En esta Tesis, se sugiere una gestión de presiones que controle los rangos de los indicadores de la presión de cabecera que más influyan en la probabilidad de roturas de tubería. Así, la presión del agua se caracteriza a través de indicadores obtenidos de la presión registrada en la cabecera de los sectores, debido a que se asume que esta presión es representativa de la presión de operación de todas las tuberías porque las pérdidas de carga son relativamente bajas y las diferencias topográficas se tienen en cuenta en el diseño de los sectores. Y los indicadores de presión, que se pueden definir como el estadístico calculado a partir de las series de la presión de cabecera sobre una ventana de tiempo, pueden proveer la información necesaria para ayudar a la toma de decisiones a los gestores del agua con el fin de reducir las roturas de tubería en las redes de distribución de agua. La primera parte de la metodología que se propone en esta Tesis trata de encontrar los indicadores de presión que influyen más en la probabilidad de roturas de tuberías. Para conocer si un indicador es influyente en la probabilidad de las roturas se comparan las estimaciones de las funciones de distribución acumulada (FDAs) de los indicadores de presiones, considerando dos situaciones: cuando se condicionan a la ocurrencia de una rotura (suceso raro) y cuando se calculan en la situación normal de operación (normal operación). Por lo general, las compañías gestoras cuentan con registros de roturas de los años más recientes y al encontrarse las tuberías enterradas se complica el acceso a la información. Por ello, se propone el uso de funciones de probabilidad que permiten reducir la incertidumbre asociada a los datos registrados. De esta forma, se determinan las funciones de distribución acumuladas (FDAs) de los valores del indicador de la serie de presión (situación normal de operación) y las FDAs de los valores del indicador en el momento de ocurrencia de las roturas (condicionado a las roturas). Si las funciones de distribución provienen de la misma población, no se puede deducir que el indicador claramente influya en la probabilidad de roturas. Sin embargo, si se prueba estadísticamente que las funciones proceden de la misma población, se puede concluir que existe una relación entre el indicador analizado y la ocurrencia de las roturas. Debido a que el número de valores del indicador de la FDA condicionada a las roturas es mucho menor que el número de valores del indicador de la FDA incondicional a las roturas, se generan series aleatorias a partir de los valores de los indicadores con el mismo número de valores que roturas registradas hay. De esta forma, se comparan las FDAs de series aleatorias del indicador con la FDA condicionada a las roturas del mismo indicador y se deduce si el indicador es influyente en la probabilidad de las roturas. Los indicadores de presión pueden depender de unos parámetros. A través de un análisis de sensibilidad y aplicando un test estadístico robusto se determina la situación en la que estos parámetros dan lugar a que el indicador sea más influyente en la probabilidad de las roturas. Al mismo tiempo, los indicadores se pueden calcular en función de dos parámetros de cálculo que se denominan el tiempo de anticipación y el ancho de ventana. El tiempo de anticipación es el tiempo (en horas) entre el final del periodo de computación del indicador de presión y la rotura, y el ancho de ventana es el número de valores de presión que se requieren para calcular el indicador de presión y que es múltiplo de 24 horas debido al comportamiento cíclico diario de la presión. Un análisis de sensibilidad de los parámetros de cálculo explica cuándo los indicadores de presión influyen más en la probabilidad de roturas. En la segunda parte de la metodología se presenta un modelo de diagnóstico bayesiano. Este tipo de modelo forma parte de los modelos estadísticos de prevención de roturas, parten de los datos registrados para establecer patrones de fallo y utilizan el teorema de Bayes para determinar la probabilidad de fallo cuando se condiciona la red a unas determinadas características. Así, a través del teorema de Bayes se comparan la FDA genérica del indicador con la FDA condicionada a las roturas y se determina cuándo la probabilidad de roturas aumenta para ciertos rangos del indicador que se ha inferido como influyente en las roturas. Se determina un ratio de probabilidad (RP) que cuando es superior a la unidad permite distinguir cuándo la probabilidad de roturas incrementa para determinados intervalos del indicador. La primera parte de la metodología se aplica a la red de distribución de la Comunidad de Madrid (España) y a la red de distribución de Ciudad de Panamá (Panamá). Tras el filtrado de datos se deduce que se puede aplicar la metodología en 15 sectores en la Comunidad de Madrid y en dos sectores, llamados corregimientos, en Ciudad de Panamá. Los resultados demuestran que en las dos redes los indicadores más influyentes en la probabilidad de las roturas son el rango de la presión, que supone la diferencia entre la presión máxima y la presión mínima, y la variabilidad de la presión, que considera la propiedad estadística de la desviación típica. Se trata, por tanto, de indicadores que hacen referencia a la dispersión de los datos, a la persistencia de la variación de la presión y que se puede asimilar en resistencia de materiales a la fatiga. La segunda parte de la metodología se ha aplicado a los indicadores influyentes en la probabilidad de las roturas de la Comunidad de Madrid y se ha deducido que la probabilidad de roturas aumenta para valores extremos del indicador del rango de la presión y del indicador de la variabilidad de la presión. Finalmente, se recomienda una gestión de presiones que limite los intervalos de los indicadores influyentes en la probabilidad de roturas que incrementen dicha probabilidad. La metodología propuesta puede aplicarse a otras redes de distribución y puede ayudar a las compañías gestoras a reducir el número de fallos en el sistema a través de la gestión de presiones. This Thesis presents a methodology for the statistical analysis of pipe breaks in water distribution networks. The methodology studies the relationship between pipe breaks and water pressure, and proposes a pressure management procedure to reduce the number of breaks that occur in such networks. One of the manifestations of the deterioration of water supply systems is frequent pipe breaks. System failures are one of the major challenges faced by water utilities, due to their associated social, economic and environmental costs. For all these reasons, water utilities aim at reducing the problem of break occurrence to as great an extent as possible. Water distribution networks can be divided into areas or sectors, which facilitates the control of the network. These areas may be independent or isolated by valves, as it usually happens in developing countries. Alternatively, they can be hydraulically interconnected. The implementation of pressure management strategies is usually carried out through pressure-reducing valves (PRV). These valves are installed at the head of the sectors and, although the inflow may vary significantly, they control the downstream pressure. The most popular methods of pressure management consist of pressure reduction, which is the common form of control, pressure sustaining, prevention and/or alleviation of pressure surges or large variations in pressure, and level/altitude control. From 2005 onwards, the effects of pressure management on burst frequencies have become more widely recognized in the technical literature. This thesis suggests a pressure management that controls the pressure indicator ranges most influential on the probability of pipe breaks. Operating pressure in a sector is characterized by means of a pressure indicator at the head of the DMA, as head losses are relatively small and topographical differences were accounted for at the design stage. The pressure indicator, which may be defined as the calculated statistic from the time series of pressure head over a specific time window, may provide necessary information to help water utilities to make decisions to reduce pipe breaks in water distribution networks. The first part of the methodology presented in this Thesis provides the pressure indicators which have the greatest impact on the probability of pipe breaks to be determined. In order to know whether a pressure indicator influences the probability of pipe breaks, the proposed methodology compares estimates of cumulative distribution functions (CDFs) of a pressure indicator through consideration of two situations: when they are conditioned to the occurrence of a pipe break (a rare event), and when they are not (a normal operation). Water utilities usually have a history of failures limited to recent periods of time, and it is difficult to have access to precise information in an underground network. Therefore, the use of distribution functions to address such imprecision of recorded data is proposed. Cumulative distribution functions (CDFs) derived from the time series of pressure indicators (normal operation) and CDFs of indicator values at times coincident with a reported pipe break (conditioned to breaks) are compared. If all estimated CDFs are drawn from the same population, there is no reason to infer that the studied indicator clearly influences the probability of the rare event. However, when it is statistically proven that the estimated CDFs do not come from the same population, the analysed indicator may have an influence on the occurrence of pipe breaks. Due to the fact that the number of indicator values used to estimate the CDF conditioned to breaks is much lower in comparison with the number of indicator values to estimate the CDF of the unconditional pressure series, and that the obtained results depend on the size of the compared samples, CDFs from random sets of the same size sampled from the unconditional indicator values are estimated. Therefore, the comparison between the estimated CDFs of random sets of the indicator and the estimated CDF conditioned to breaks allows knowledge of if the indicator is influential on the probability of pipe breaks. Pressure indicators depend on various parameters. Sensitivity analysis and a robust statistical test allow determining the indicator for which these parameters result most influential on the probability of pipe breaks. At the same time, indicators can be calculated according to two model parameters, named as the anticipation time and the window width. The anticipation time refers to the time (hours) between the end of the period for the computation of the pressure indicator and the break. The window width is the number of instantaneous pressure values required to calculate the pressure indicator and is multiple of 24 hours, as water pressure has a cyclical behaviour which lasts one day. A sensitivity analysis of the model parameters explains when the pressure indicator is more influential on the probability of pipe breaks. The second part of the methodology presents a Bayesian diagnostic model. This kind of model belongs to the class of statistical predictive models, which are based on historical data, represent break behavior and patterns in water mains, and use the Bayes’ theorem to condition the probability of failure to specific system characteristics. The Bayes’ theorem allows comparing the break-conditioned FDA and the unconditional FDA of the indicators and determining when the probability of pipe breaks increases for certain pressure indicator ranges. A defined probability ratio provides a measure to establish whether the probability of breaks increases for certain ranges of the pressure indicator. The first part of the methodology is applied to the water distribution network of Madrid (Spain) and to the water distribution network of Panama City (Panama). The data filtering method suggests that the methodology can be applied to 15 sectors in Madrid and to two areas in Panama City. The results show that, in both systems, the most influential indicators on the probability of pipe breaks are the pressure range, which is the difference between the maximum pressure and the minimum pressure, and pressure variability, referred to the statistical property of the standard deviation. Therefore, they represent the dispersion of the data, the persistence of the variation in pressure and may be related to the fatigue in material resistance. The second part of the methodology has been applied to the influential indicators on the probability of pipe breaks in the water distribution network of Madrid. The main conclusion is that the probability of pipe breaks increases for the extreme values of the pressure range indicator and of the pressure variability indicator. Finally, a pressure management which limits the ranges of the pressure indicators influential on the probability of pipe breaks that increase such probability is recommended. The methodology presented here is general, may be applied to other water distribution networks, and could help water utilities reduce the number of system failures through pressure management.

Interval-based ranking in noisy evolutionary multiobjective optimization

As one of the most competitive approaches to multi-objective optimization, evolutionary algorithms have been shown to obtain very good results for many realworld multi-objective problems. One of the issues that can affect the performance of these algorithms is the uncertainty in the quality of the solutions which is usually represented with the noise in the objective values. Therefore, handling noisy objectives in evolutionary multi-objective optimization algorithms becomes very important and is gaining more attention in recent years. In this paper we present ?-degree Pareto dominance relation for ordering the solutions in multi-objective optimization when the values of the objective functions are given as intervals. Based on this dominance relation, we propose an adaptation of the non-dominated sorting algorithm for ranking the solutions. This ranking method is then used in a standardmulti-objective evolutionary algorithm and a recently proposed novel multi-objective estimation of distribution algorithm based on joint variable-objective probabilistic modeling, and applied to a set of multi-objective problems with different levels of independent noise. The experimental results show that the use of the proposed method for solution ranking allows to approximate Pareto sets which are considerably better than those obtained when using the dominance probability-based ranking method, which is one of the main methods for noise handling in multi-objective optimization.

Purification of ribonucleotide reductase subunits Y1, Y2, Y3, and Y4 from yeast: Y4 plays a key role in diiron cluster assembly

Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides. Class I RNRs are composed of two types of subunits: RNR1 contains the active site for reduction and the binding sites for the nucleotide allosteric effectors. RNR2 contains the diiron-tyrosyl radical (Y⋅) cofactor essential for the reduction process. Studies in yeast have recently identified four RNR subunits: Y1 and Y3, Y2 and Y4. These proteins have been expressed in Saccharomyces cerevisiae and in Escherichia coli and purified to ≈90% homogeneity. The specific activity of Y1 isolated from yeast and E. coli is 0.03 μmol⋅min−1⋅mg−1 and of (His)6-Y2 [(His)6-Y2-K387N] from yeast is 0.037 μmol⋅min−1⋅mg−1 (0.125 μmol⋅min−1⋅mg−1). Y2, Y3, and Y4 isolated from E. coli have no measurable activity. Efforts to generate Y⋅ in Y2 or Y4 using Fe2+, O2, and reductant have been unsuccessful. However, preliminary studies show that incubation of Y4 and Fe2+ with inactive E. coli Y2 followed by addition of O2 generates Y2 with a specific activity of 0.069 μmol⋅min−1⋅mg−1 and a Y⋅. A similar experiment with (His)6-Y2-K387N, Y4, O2, and Fe2+ results in an increase in its specific activity to 0.30 μmol⋅min−1⋅mg−1. Studies with antibodies to Y4 and Y2 reveal that they can form a complex in vivo. Y4 appears to play an important role in diiron-Y⋅ assembly of Y2.

A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase

Editing of RNA changes the read-out of information from DNA by altering the nucleotide sequence of a transcript. One type of RNA editing found in all metazoans uses double-stranded RNA (dsRNA) as a substrate and results in the deamination of adenosine to give inosine, which is translated as guanosine. Editing thus allows variant proteins to be produced from a single pre-mRNA. A mechanism by which dsRNA substrates form is through pairing of intronic and exonic sequences before the removal of noncoding sequences by splicing. Here we report that the RNA editing enzyme, human dsRNA adenosine deaminase (DRADA1, or ADAR1) contains a domain (Zα) that binds specifically to the left-handed Z-DNA conformation with high affinity (KD = 4 nM). As formation of Z-DNA in vivo occurs 5′ to, or behind, a moving RNA polymerase during transcription, recognition of Z-DNA by DRADA1 provides a plausible mechanism by which DRADA1 can be targeted to a nascent RNA so that editing occurs before splicing. Analysis of sequences related to Zα has allowed identification of motifs common to this class of nucleic acid binding domain.

Quantitative high performance liquid chromatography/tandem mass spectrometric analysis of the four classes of F2-isoprostanes in human urine

Isoprostanes (iPs) are free radical catalyzed prostaglandin isomers. Analysis of individual isomers of PGF2α—F2-iPs—in urine has reflected lipid peroxidation in humans. However, up to 64 F2-iPs may be formed, and it is unknown whether coordinate generation, disposition, and excretion of F2-iPs occurs in humans. To address this issue, we developed methods to measure individual members of the four structural classes of F2-iPs, using liquid chromatography/tandem mass spectrometry (LC/MS/MS), in which sample preparation is minimized. Authentic standards of F2-iPs of classes III, IV, V, and VI were used to identify class-specific ions for multiple reaction monitoring. Using iPF2α-VI as a model compound, we demonstrated the reproducibility of the assay in human urine. Urinary levels of all F2-iPs measured were elevated in patients with familial hypercholesterolemia. However, only three of eight F2-iPs were elevated in patients with congestive heart failure, compared with controls. Paired analyses by GC/MS and LC/MS/MS of iPF2α-VI in hypercholesterolemia and of 8,12-iso-iPF2α-VI in congestive heart failure were highly correlated. This approach will permit high throughput analysis of multiple iPs in human disease.

Ligation of intestinal epithelial CD1d induces bioactive IL-10: Critical role of the cytoplasmic tail in autocrine signaling

The intestinal epithelium is anatomically positioned to serve as the critical interface between the lumen and the mucosal immune system. In addition to MHC class I and II antigens, intestinal epithelia constitutively express the nonclassical MHC molecule CD1d, a transmembrane molecule with a short cytoplasmic tail expressed as a β2-microglobulin-associated 48-kDa glycoprotein and novel β2-microglobulin-independent 37-kDa nonglycosylated protein on intestinal epithelia. At present, it is not known whether extracellular ligands can signal intestinal epithelial CD1d. To define signaling of CD1d cytoplasmic tail, retrovirus-mediated gene transfer was used to generate stable cell lines expressing wild-type CD1d or a chimeric molecule (extracellular CD1d and cytoplasmic CD1a), and surface CD1d was triggered by antibody crosslinking. Although wild-type CD1d was readily activated (tyrosine phosphorylation), no demonstrable signal was evident in cell lines expressing the chimeric molecule. Subsequent studies revealed that anti-CD1d crosslinking specifically induces epithelial IL-10 mRNA and protein and is blocked by the tyrosine kinase inhibitor genistein. Further studies addressing epithelial-derived IL-10 revealed that anti-CD1d crosslinking attenuates IFN-γ signaling and that such attenuation is reversed by addition of functionally inhibitory IL-10 antibodies. These results define signaling through surface CD1d, and, importantly, they demonstrate that this pathway may serve to dampen epithelial proinflammatory signals.