Approximate Relational Reasoning for Probabilistic Programs

La seguridad verificada es una metodología para demostrar propiedades de seguridad de los sistemas informáticos que se destaca por las altas garantías de corrección que provee. Los sistemas informáticos se modelan como programas probabilísticos y para probar que verifican una determinada propiedad de seguridad se utilizan técnicas rigurosas basadas en modelos matemáticos de los programas. En particular, la seguridad verificada promueve el uso de demostradores de teoremas interactivos o automáticos para construir demostraciones completamente formales cuya corrección es certificada mecánicamente (por ordenador). La seguridad verificada demostró ser una técnica muy efectiva para razonar sobre diversas nociones de seguridad en el área de criptografía. Sin embargo, no ha podido cubrir un importante conjunto de nociones de seguridad “aproximada”. La característica distintiva de estas nociones de seguridad es que se expresan como una condición de “similitud” entre las distribuciones de salida de dos programas probabilísticos y esta similitud se cuantifica usando alguna noción de distancia entre distribuciones de probabilidad. Este conjunto incluye destacadas nociones de seguridad de diversas áreas como la minería de datos privados, el análisis de flujo de información y la criptografía. Ejemplos representativos de estas nociones de seguridad son la indiferenciabilidad, que permite reemplazar un componente idealizado de un sistema por una implementación concreta (sin alterar significativamente sus propiedades de seguridad), o la privacidad diferencial, una noción de privacidad que ha recibido mucha atención en los últimos años y tiene como objetivo evitar la publicación datos confidenciales en la minería de datos. La falta de técnicas rigurosas que permitan verificar formalmente este tipo de propiedades constituye un notable problema abierto que tiene que ser abordado. En esta tesis introducimos varias lógicas de programa quantitativas para razonar sobre esta clase de propiedades de seguridad. Nuestra principal contribución teórica es una versión quantitativa de una lógica de Hoare relacional para programas probabilísticos. Las pruebas de correción de estas lógicas son completamente formalizadas en el asistente de pruebas Coq. Desarrollamos, además, una herramienta para razonar sobre propiedades de programas a través de estas lógicas extendiendo CertiCrypt, un framework para verificar pruebas de criptografía en Coq. Confirmamos la efectividad y aplicabilidad de nuestra metodología construyendo pruebas certificadas por ordendor de varios sistemas cuyo análisis estaba fuera del alcance de la seguridad verificada. Esto incluye, entre otros, una meta-construcción para diseñar funciones de hash “seguras” sobre curvas elípticas y algoritmos diferencialmente privados para varios problemas de optimización combinatoria de la literatura reciente. ABSTRACT The verified security methodology is an emerging approach to build high assurance proofs about security properties of computer systems. Computer systems are modeled as probabilistic programs and one relies on rigorous program semantics techniques to prove that they comply with a given security goal. In particular, it advocates the use of interactive theorem provers or automated provers to build fully formal machine-checked versions of these security proofs. The verified security methodology has proved successful in modeling and reasoning about several standard security notions in the area of cryptography. However, it has fallen short of covering an important class of approximate, quantitative security notions. The distinguishing characteristic of this class of security notions is that they are stated as a “similarity” condition between the output distributions of two probabilistic programs, and this similarity is quantified using some notion of distance between probability distributions. This class comprises prominent security notions from multiple areas such as private data analysis, information flow analysis and cryptography. These include, for instance, indifferentiability, which enables securely replacing an idealized component of system with a concrete implementation, and differential privacy, a notion of privacy-preserving data mining that has received a great deal of attention in the last few years. The lack of rigorous techniques for verifying these properties is thus an important problem that needs to be addressed. In this dissertation we introduce several quantitative program logics to reason about this class of security notions. Our main theoretical contribution is, in particular, a quantitative variant of a full-fledged relational Hoare logic for probabilistic programs. The soundness of these logics is fully formalized in the Coq proof-assistant and tool support is also available through an extension of CertiCrypt, a framework to verify cryptographic proofs in Coq. We validate the applicability of our approach by building fully machine-checked proofs for several systems that were out of the reach of the verified security methodology. These comprise, among others, a construction to build “safe” hash functions into elliptic curves and differentially private algorithms for several combinatorial optimization problems from the recent literature.

Comparison of linear and non-linear 2D+T registration methods for DE-MRI cardiac perfusion studies

A series of motion compensation algorithms is run on the challenge data including methods that optimize only a linear transformation, or a non-linear transformation, or both – first a linear and then a non-linear transformation. Methods that optimize a linear transformation run an initial segmentation of the area of interest around the left myocardium by means of an independent component analysis (ICA) (ICA-*). Methods that optimize non-linear transformations may run directly on the full images, or after linear registration. Non-linear motion compensation approaches applied include one method that only registers pairs of images in temporal succession (SERIAL), one method that registers all image to one common reference (AllToOne), one method that was designed to exploit quasi-periodicity in free breathing acquired image data and was adapted to also be usable to image data acquired with initial breath-hold (QUASI-P), a method that uses ICA to identify the motion and eliminate it (ICA-SP), and a method that relies on the estimation of a pseudo ground truth (PG) to guide the motion compensation.

Negative density dependence and environmental heterogeneity effects on tree ferns across succession in a tropical montane forest.

Although tree ferns are an important component of temperate and tropical forests, very little is known about their ecology. Their peculiar biology (e.g., dispersal by spores and two-phase life cycle) makes it difficult to extrapolate current knowledge on the ecology of other tree species to tree ferns. In this paper, we studied the effects of negative density dependence (NDD) and environmental heterogeneity on populations of two abundant tree fern species, Cyathea caracasana and Alsophila engelii, and how these effects change across a successional gradient. Species patterns harbor information on processes such as competition that can be easily revealed using point pattern analysis techniques. However, its detection may be difficult due to the confounded effects of habitat heterogeneity. Here, we mapped three forest plots along a successional gradient in the montane forests of Southern Ecuador. We employed homogeneous and inhomogeneous K and pair correlation functions to quantify the change in the spatial pattern of different size classes and a case-control design to study associations between juvenile and adult tree ferns. Using spatial estimates of the biomass of four functional tree types (short- and long-lived pioneer, shade- and partial shade-tolerant) as covariates, we fitted heterogeneous Poisson models to the point pattern of juvenile and adult tree ferns and explored the existence of habitat dependencies on these patterns. Our study revealed NDD effects for C. caracasana and strong environmental filtering underlying the pattern of A. engelii. We found that adult and juvenile populations of both species responded differently to habitat heterogeneity and in most cases this heterogeneity was associated with the spatial distribution of biomass of the four functional tree types. These findings show the effectiveness of factoring out environmental heterogeneity to avoid confounding factors when studying NDD and demonstrate the usefulness of covariate maps derived from mapped communities.

Persuasive system design methods to deliver a cardio-rehabilitation program of post mi outpatients

Las enfermedades no transmisibles provocan cada ano 38 millones de fallecimientos en el mundo. Entre ellas, tan solo cuatro enfermedades son responsables del 82% de estas muertes: las enfermedades cardiovasculares, las enfermedades crónicas respiratorias, la diabetes, y el cáncer. Se prevé que estas cifras aumenten en los próximos anos, ya que las tendencias indican que en el año 2030 las muertes por esta causa ascenderán a 53 millones de personas. La Organización Mundial de la Salud (OMS) considera importante buscar soluciones para afrontar esta situación y ha solicitado a los gobiernos del mundo la implementación de intervenciones para mejorar los hábitos de vida de las personas y reducir así el riesgo de desarrollo de enfermedades no trasmisibles. Cada año se producen 32 millones de infartos de miocardio y derrames celebrales, de los cuales 12.5 son mortales. En el mundo entre el 40% y 75% de la víctimas de un infarto de miocardio mueren antes de su ingreso en el hospital. En los casos que sobreviven, la adopción de un estilo de vida saludable puede evitar infartos sucesivo, y supone un ahorro potencial de 6 billones de euros al año. La rehabilitación cardiaca es un programa individualizado que aplica un método multidisciplinar para ayudar al paciente a recuperar su condición física, a gestionar la enfermedad cardiovascular y sus comorbilidades, a adoptar hábitos de vida saludables, y a promover su salud mental. La rehabilitación cardiaca requiere la total involucración y motivación del paciente, solo de esta manera se podrán promover hábitos saludables y mejorar la gestión y prevención de su enfermedad. Aunque la participación en los programas de rehabilitación cardiaca es baja, hoy en día existen programas de rehabilitación cardiaca que el paciente puede realizar en su casa. Estos suponen una solución prometedora para aumentar la participación. La rehabilitación cardiaca se considera una intervención integral donde los modelos de psicología de la salud son aplicados para promover un cambio en el estilo de vida de las personas así como para ayudarles a afrontar su propia enfermedad. Existen métodos para implementar cambios de hábitos y de aptitud, y también se considera muy relevante promover no solo el bienestar físico sino también el mental. Existen tecnologías que promueven los cambios de comportamientos en los seres humanos. En concreto, las tecnologías persuasivas y los sistemas de apoyo al cambio de comportamientos modelan las características, las estrategias y los métodos de diseño para promover cambios usando la tecnología. Pero estos modelos tienen algunas limitaciones: todavía no se ha definido que rol tienen las emociones en el cambio de comportamientos y como traducir los métodos de la psicología de la salud en la tecnología. Esta tesis se centra en tres elementos que tienen un rol clave en los cambios de hábitos y actitud: el estado físico, el estado mental, y la tecnología. -Estado de salud: un estado de salud critico puede modificar la actitud del ser humano respecto al cambio. A la vez un buen estado de salud hace que la necesidad del cambio sea menos percibida. -Estado emocional: la actitud tiene un componente afectivo. Los estados emocionales negativos pueden reducir la habilidad de una persona para adoptar nuevos comportamientos. La salud mental es la situación ideal donde los individuos tienen predisposición a los cambios. La tecnología puede ayudar a las personas a adoptar nuevos hábitos, así como a mantener una salud física y mental. Este trabajo de investigación se centra en el diseño de tecnologías para la mejora del estado físico y emocional de las personas. Se ha propuesto un marco de diseño llamado “Well.Be.Sign”. El marco se basa en tres aspectos: El marco teórico: representa los elementos que se tienen que definir para diseñar tecnologías para promover el bienestar de las personas. -El diagrama de influencia: presenta las fuerzas de ‘persuasión’ en el contexto de la salud. El rol de las tecnologías persuasivas ha sido contextualizado en una dimensión donde otros elementos influencian el usuario.  El proceso de diseño: describe el proceso de diseño utilizando una metodología iterativa e incremental que aplica una combinación de métodos de diseño existentes (Diseño Orientado a Objetivos, Diseño de Sistemas Persuasivos) así como elementos originales de este trabajo de investigación. Los métodos se han aplicados para diseñar un sistema que ofrezca un programa de tele-rehabilitación cardiaca. Inicialmente se ha diseñado un prototipo de acuerdo con las necesidades del usuario. En segundo lugar, el prototipo se ha extendido especificando la intervención requerida para al programa de rehabilitación cardiaca. Finalmente el sistema se ha desarrollado y validado en un ensayo clínico con grupo control, donde se observaron las variaciones del estado cardiovascular, el nivel de conocimiento acerca de la enfermedad, la percepción de la enfermedad, la persistencia de hábitos saludables, y la aceptabilidad del sistema. Los resultados muestran que el grupo de intervención tiene una superior capacidad cardiovascular, mejor conocimiento acerca de la enfermedad, y más percepción de control de la enfermedad. Asimismo, en algunos casos se ha registrado persistencia de los hábitos de ejercicios 6 meses después del uso del sistema. Otros dos estudios se han presentado para demonstrar la relevancia del estado emocional del usuario en el diseño de aplicaciones para la promoción del bienestar.  En personas con una grave enfermedad crónica como la insuficiencia cardiaca, donde se ha presentado las conexiones entre estado de salud y estado emocional. En el estudio se ensena la relaciones que tienen los síntomas y las emociones negativas y como un estado negativo emocional puede empeorar la condición física del paciente. -Personas con trastornos del humor: el estudio muestra como las emociones pueden tener un impacto en la percepción de la tecnología por parte del usuario. ABSTRACT Noncommunicable diseases (NCDs) cause the death of 38 million people every year. Four major NCDs are responsible for 82% of these deaths: cardio vascular disease, chronic respiratory disease, diabetes and cancer. These pandemic numbers are projected to raise to 53 million deaths in 2030, and for this reason the assembly of the World Health Organization (WHO) considers communicable diseases as an urgent need to be addressed. It is also a trend to advocate the adoption of mobile technology to deliver health services and to promote healthy behaviours among citizens, but adopting healthS promoting lifestyle is still a difficult task facing human tendencies. Within this context, there is a promising opportunity: persuasive technologies. These technologies are intentionally designed to change a person’s attitudes or behaviours; when applied in this context, than can be used to change health-related attitudes, beliefs, and behaviours. Each year there are 32 million heart attacks and strokes globally, of which about 12.5 million are fatal. Worldwide between 40 and 75% of all heart-attack victims die before reaching hospital. Avoiding a second heart attack by improving adherence to lifestyle and medication regimens has a cost saving potential of around €6 billion per year. In most of the cases the cardiovascular event has been provoked by unhealthy lifestyle. Furthermore, after an MI event the patient's decision to adopt or not healthier behaviour will influence the progress of the disease. Cardio-rehabilitation is an individualized program that follows a multidisciplinary approach to support the user to recover from the Myocardial Infarction, manage the Cardio Vascular Disease and the comorbidities, adopt healthy habits, and cope with any emotional distress. Cardio- rehabilitation requires patient participation and willingness to perform behavioral modifications and change the attitude toward the management and prevention of the disease. Participation in the Cardio Rehabilitation program is not high; the home-based rehabilitation program is a promising solution to increase participation. Nowadays cardio rehabilitation is considered a comprehensive intervention in which models of health psychology are applied to promote the behaviour change of the individuals. Relevant methods that have been successfully applied to foster healthy habits include the Health Belief Model and the Trans Theoretical Model. Studies also demonstrate the importance to promote not only the physical but also the mental well being of the individuals. The idea of also promoting behaviour change using technologies has been defined by the literature as persuasive technologies or behaviour change support systems, in which the features, the strategies and the design method have been modelled to foster the behaviour change using technology. Limitations have been found in this model: there is still research to be done on the role of the emotions and how psychological health intervention can be translated into computer methods. This research focuses on three elements that could foster behaviour change in individuals: the physical and emotional status of the person, and the technology. Every component can influence the user's attitude and behaviour in the following ways: ' Physical status: bad physical status could change human attitude toward the necessity to adopt health behaviours; at the same time, good health status reduces the need to adopt healthy habits. ' Emotional status: the attitude has an affective component, negative emotional state can reduce the ability of a person to adopt new behaviours, and mental well being is the ideal situation in which individuals have a predisposition to adopt healthy behaviours. ' Technology: it can help users to adopt new behaviours and can also be support to promote physical and emotional status. Following this approach the idea driven in this research is that technology that is designed to improve the physical status and the emotional status of the individual could better foster behaviour change. According to this principle, the Well.Be.Sign framework has been proposed. The framework is based on three views: ' The theoretical framework: it represents the patterns that have to be defined to design the technologies to promote well being. ' The influence diagram: it shows the persuasive forces in the context of health care. The role of the persuasive technologies is contextualized in a wider universe where other factors and persuasive forces influence a patient. ' The design process: it shows the process of design using an iterative, incremental methodology that applies a combination of existing methodologies (Goal Directed Design and Persuasive System Design) and others that are original to this research. The methods have been applied to design a system to deliver cardio rehabilitation at home: first a prototype has been defined according to the user’s needs, then it has been extended with the specific intervention required for the cardio–rehabilitation, finally the system has been developed and validated in a controlled clinical study in which the cardiovascular fitness, the level of knowledge, the perception of the illness, the persistence of healthy habits and the system acceptance (only the intervention group) were measured. The results show that the intervention group increased cardiovascular capacity, knowledge, feeling of control of illness and perceived benefits of exercise at the end of the study. After six months of the study, a followSup of the exercise habits was performed. Some individuals of the intervention group continued to be engaged in the running exercise sessions promoted in the designed system. Two other cases have been presented to demonstrate the foundations of the Well.Be.Sign’s approach to promote both physical and emotional status: ' People affected by Heart Failure, in which a bidirectional connection between health status and emotions has been discussed with patients. Two correlations were demonstrated: the relationship between symptoms and negative emotional response, and that negative emotional status is correlated with worsening of chronic conditions. ' People with mood disorders: the study shows that emotions could also impact how the user perceives the technology.

Lo permanente en lo efímero: Pabellones de Exposiciones Universales, hitos de la arquitectura de la segunda posguerra

Los Pabellones de las Exposiciones Universales suelen considerarse dentro de las arquitecturas efímeras, pero habría que puntualizar que toda construcción tiene su tiempo y su periodo de extinción pudiendo ser éstos indefinidos, lo permanente en lo efímero. Muchas de las obras míticas del siglo XX existieron sólo durante unos meses, en escenarios efímeros, modificando el curso de la arquitectura con unas pocas imágenes, lo que llevaría a cuestionar si las circunstancias por las que no han sobrevivido o lo han hecho en circunstancias poco comunes, no se deben tanto a una condición efímera sino a su carácter experimental. Determinadas Exposiciones Universales fueron plataforma para que los pabellones, hitos con los que se ha construido una parte significativa de la Historia de la Arquitectura contemporánea, pasaran a convertirse en mitos, por su distancia en el tiempo, porque ya no existen y porque a veces de ellos sólo nos queda una anticuada y limitada imaginería. Las diversas Historias de la Arquitectura ponen de manifiesto la importancia de algunos pabellones y el papel que ejercieron, ejercen y ejercerán algunos de los construidos para determinadas Exposiciones Universales, pues son el testimonio de que se mantienen vivos, permaneciendo en el tiempo, desempeñando cada uno una función, bien de base para nuevos avances tecnológicos o constructivos, bien para experimentar nuevas formas de habitar, bien para educar, bien para encumbrar a sus autores hasta entonces apenas conocidos. Tanto los que se han mantenido en pie, como los que han sido trasladados y reconstruidos en un nuevo emplazamiento, o incluso los que siguieron su destino fatal y se convirtieron en arquitecturas ausentes, pero que por lo que supusieron de innovación y experimentación, todos han permanecido vivos en la arquitectura de hoy en día. Esta tesis estudia el conjunto de factores que contribuyeron a conferirles esa condición de hito, qué tipo de publicaciones hablan de ellos, en qué términos se tratan y en qué medida los relacionan con la producción de la época y/o de su autor, qué aspectos destacan, cuáles son los valores icónicos que se han ido estableciendo con el paso del tiempo…Qué es lo que permanece. Por otra parte, también aborda en qué medida su condición de construcción efímera, y gracias a su inherente necesidad de desaparecer físicamente, favoreciendo su ausencia en el recuerdo, lo que los ha dotado de representatividad. Esto podría resultar hoy en día algo contradictorio, dado el gran valor concedido a la imagen en la sociedad actual hasta el punto de convertirse en un componente esencial de la representatividad: la imagen sustituye al recuerdo pareciendo que lo que carezca de manifestación física en realidad no existiera, hasta llegar a hacerle perder toda capacidad de representación. Sin embargo, y considerando la imagen como elemento esencial de lo icónico, la reconstrucción de los pabellones una vez concluidas las exposiciones, en muchos casos no ha hecho más que potenciar su valor como arquitecturas efímeras, ya que desposeídos de su carácter temporal, los pabellones de las exposiciones pierden su razón de ser. El Pabellón de España de Corrales y Molezún para la EXPO Bruselas’58 es un claro ejemplo de ello, como se mostrará en el desarrollo de la tesis. En la tesis se exponen los distintos casos de los pabellones elegidos, rastreando, fundamentalmente en las publicaciones periódicas, el papel que en cada uno de ellos ejerció su destino final que, a pesar de no ser el objetivo o fin de la presente tesis, sí podría haber contribuido en algunos casos a dotarle de esa categoría de hito en la historia de la arquitectura. Se trata en definitiva de rastrear las vicisitudes que los han conducido a su condición de referentes arquitectónicos, de hitos de la Historia de la Arquitectura. El estudio se centra en Pabellones de las Exposiciones Universales de Bruselas’58, Montreal’67 y Osaka’70 por dos motivos fundamentales: el primero, su catalogación por el Bureau International des Expositions (BIE) como Exposiciones Universales de 1ª categoría; y el segundo, el período en el que se celebraron, período comprendido entre los años 1945 a 1970, años de profundos y determinantes cambios en la arquitectura y en los que tiene lugar el desarrollo y posterior revisión de la modernidad tras la 2ª Guerra Mundial. Se analiza la trayectoria bibliográfica de los pabellones más nombrados de estas tres Exposiciones Universales que son: de Bruselas ’58, el Pabellón de la República Federal de Alemania, de Egon Eiermann y Sep Ruf; el Pabellón Philips de Le Corbusier, y el Pabellón de España, de José Antonio Corrales y Ramón Molezún; de Montreal ’67, el Pabellón de la República Federal de Alemania, de Frei Otto, y el Pabellón de Estados Unidos, de Richard Buckminster Fuller; y de Osaka ’70, el Theme Pavilion, de Kenzo Tange, el Takara Beautilion, de Kisho Kurokawa, y el Pabellón del Grupo Fuji, de Yutaka Murata. Mediante el análisis se detecta que, ya en las revistas coetáneas a las exposiciones, estos pabellones se señalaban como edificios importantes para la historia de la arquitectura futura. Hecho que se constata con la aparición de los mismos en las historias, incluso en las más recientes, lo que demuestra su condición de hitos en la Historia de la Arquitectura ya consolidada. ABSTRACT Pavilions of the Universal Exhibitions are often considered as ephemeral architecture. However it is worth mentioning that every construction has its time and its extinction period and both of them could be indefinite/infinite, the permanent in the ephemeral. Many of the iconic works of the twentieth century lasted only for a few months, in ephemeral scenarios, changing the course of architecture but not with many images. This leads to question whether their survival under special circumstances or their extinction is mainly due to their experimental nature, and not so much to their ephemeral condition. Pavilions are at the basis of a significant part of the history of contemporary architecture. Specific Universal Exhibitions served as platforms for these landmarks to become myths, be it because of their endurance, or because they no longer exist, or even because in some cases we only have a limited and outdated imagery of them. The different Histories of Architecture highlight the importance of some pavilions and the influence they have had, have and will have some of those that were built for particular Universal Exhibitions. They are a live testimony, lasting over time, playing a specific role as basis for new technological or constructive breakthroughs; to experience new ways of living; or to educate or to raise the profile of their authors hitherto little known. Thanks to their experimental or innovative approach, some pavilions enduring overtime or that have been moved and rebuilt in a new location, or even those that followed their fate and became absent architectures, are still alive in today’s architecture. This thesis analyses the set of elements that contributed to confer the status of landmark to pavilions: what kind of publications speak of them; how they are referred to and the extent to which they are linked to their contemporary production time and / or to their author; what are elements that make them stand out; what are the iconic values that have been established as time goes by and what are those that are still valid…What is it that remains. It also assesses to what extend the condition of pavilion constructions is ephemeral. And finally, what confers them representativeness, giving their inherent need to physically disappear, favoring their absence in the memory. Today this may result somewhat contradictory as the high value of images in contemporary society has made them an essential component of representativeness. They replace remembrances to the point that it seems that what lacks physical manifestation doesn’t exist anymore, and therefore loses representation capacity. However, and considering images as an essential element of what is iconic, in most cases the reconstruction of pavilions upon completion of the exhibitions has leveraged their value as ephemeral architectures; although once deprived of their temporary character, they would lose their reason to exist. The Pavilion of Spain Corrales and Molezún for the Brusels'58 EXPO is a clear example of this, as described in the development of this document. This thesis explores the case of specific pavilions and assesses the role each one had in their final destination, by mainly tracking them in regular publications. Even though the latter is not the objective or the purpose of this thesis, the final destination of these pavilions may have contributed in some cases to grant them their landmark status in the history of architecture. Actually, this thesis is about tracking the events that have led to grant these pavilions their condition as architectural references, as landmark in the history of architecture. The study focuses on pavilions of the Universal Exhibition Brussels'58, Montreal'67 and Osaka'70 for two main reasons: first, their classification by the Bureau International des Expositions (BIE) and Universal Exhibitions 1st category; and second, the period in which they were held, from 1945 to 1970, a time of profound and decisive changes in the architecture and in the development and subsequent revision of modernity after the II World. It analyzes the bibliographic path of the most cited pavilions in the three Universal Exhibitions: in Brussels '58, the pavilion of the RFA by Egon Eiermann and Sep Rup, the pavilion of Philips by Le Corbusier and the Spain pavilion from José Antonio Corrales and Ramón Molezún; in Montreal '67 the pavilion of RFA by Frei Otto and the United States pavilion by Richard Buckminster Fuller; and in Osaka '70, the Theme Pavilion by Kenzo Tange, the Takara Beautilion by Kisho Kurokawa and the Fuji Group pavilion by Yutaka Murata. Through the analysis it is noticeable that in the contemporary publications to the exhibitions, these pavilions were already signaled out as relevant buildings to the future architecture history. The fact that they became part of the history themselves, even in the most recent times, is a prove of their condition as milestones of the consolidated History of Architecture.

La geometría del agua : mecanismos arquitectónicos de manipulación espacial

Este trabajo de investigación trata las relaciones del agua con la arquitectura. El agua es un elemento con capacidad arquitectónica para generar atmósferas, por lo que el enfoque del estudio será el empleo de esta como un importante componente que participa en el proyecto arquitectónico. Esta vinculación entre agua y arquitectura es un tema atemporal, aunque hoy en día parece haber sido olvidado. La tesis busca dar respuesta a una serie de preguntas planteadas ¿por qué el agua sigue acompañado a la arquitectura en nuestros días? ¿se conoce lo que esta puede aportar? ¿existe un medio por el que se pueda conocer cómo se realiza esta vinculación con la arquitectura? Se plantea como hipótesis la existencia de unos mecanismos arquitectónicos que regulan la manipulación espacial mediante el agua. La detección y el estudio de estos mecanismos permitirá responder a las preguntas planteadas y analizar en profundidad la capacidad del agua para modificar la arquitectura. El enfoque de la investigación se hace desde un punto de vista crítico y científico, evitando una visión romántica. La utilización del agua como elemento arquitectónico durante siglos y por diferentes culturas induce a la reflexión y al estudio en busca de unos parámetros comunes. La tesis se estructura en cuatro capítulos que analizan momentos en los que el agua se emplea como un elemento arquitectónico fundamental. Se han localizado diversos lugares y momentos históricos, tanto antiguos como contemporáneos, lo que permitirá contemplar el empleo del agua desde diferentes perspectivas, identificar y seguir una línea de continuidad o de evolución en la asociación entre el agua y la arquitectura. En cada uno de los capítulos se analizarán unos casos de estudio y los correspondientes mecanismos empleados en la manipulación del agua. Para ello se ha realizado una selección de proyectos en los que el agua es determinante en la generación de los espacios. Durante el proceso de investigación se ha considerado la geometría como una herramienta clave para comprender el funcionamiento de los mecanismos del agua. En un capítulo introductorio se analiza la geometría del movimiento del agua. El objetivo de esta investigación es estudiar los mecanismos arquitectónicos de manipulación espacial realizados mediante el agua. Las conclusiones se establecen a partir de la identificación de esos mecanismos, su definición y clasificación. Finalmente se realiza un mapa de proyectos vinculados al agua mediante las conclusiones obtenidas. ABSTRACT This research deals with the relations of water with architecture. Water is an architectural element with capacity to generate atmospheres, so the study will focus on the using of this as an important component involved in the architectural project. The link between water and architecture is a timeless theme, although it seems to have been forgotten nowadays. The thesis seeks to answer several questions, why the water is still linked to architecture today? It is possible to know what it can bring? Is there any mean by which can be know how to make this link with architecture? As a hypothesis is considered the existence of certain architectural mechanisms that regulate spatial manipulation by water. The detection and study of these mechanisms will allow answer these questions and analyze in depth the ability of water to modify the architecture. The research is done from a critical and scientific focus, avoiding a romantic view. The use of water as an architectural element for centuries and by different cultures induces thought-provoking and study seeking for common parameters. The thesis is divided into four chapters that analyze certain periods of time when water is used as a basic architectural element. Places and historical moments where found and located from both ancient and contemporary, allowing to contemplate the use of water from different perspectives, identify and follow a line of continuity or evolution in the association between water and architecture. In each chapter some study cases are analyzed with their corresponding mechanisms used in handling the water. Therefore it has been done a selection of projects where water is esential for the space generation. During the research process, geometry has been considered as a tool key to understand the functioning of the water mechanisms. In an introductory chapter the geometry of water movement is analyzed. The objective of this research is to study the architectural mechanisms for spatial manipulation, made possible by the water. The conclusions are set from the identification of these mechanisms, their definition and classification. Finally a map of projects linked with water is made with the achieved conclusions.

A promoção dos bons hábitos alimentares nos alunos do 1.º e do 2.º ciclo do ensino básico

Relatório de estágio apresentado para a obtenção do grau de mestre em Ensino do 1º e do 2º ciclo do ensino básico

A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage

Checkpoints maintain the order and fidelity of the eukaryotic cell cycle, and defects in checkpoints contribute to genetic instability and cancer. Much of our current understanding of checkpoints comes from genetic studies conducted in yeast. In the fission yeast Schizosaccharomyces pombe (Sp), SpRad3 is an essential component of both the DNA damage and DNA replication checkpoints. The SpChk1 and SpCds1 protein kinases function downstream of SpRad3. SpChk1 is an effector of the DNA damage checkpoint and, in the absence of SpCds1, serves an essential function in the DNA replication checkpoint. SpCds1 functions in the DNA replication checkpoint and in the S phase DNA damage checkpoint. Human homologs of both SpRad3 and SpChk1 but not SpCds1 have been identified. Here we report the identification of a human cDNA encoding a protein (designated HuCds1) that shares sequence, structural, and functional similarity to SpCds1. HuCds1 was modified by phosphorylation and activated in response to ionizing radiation. It was also modified in response to hydroxyurea treatment. Functional ATM protein was required for HuCds1 modification after ionizing radiation but not after hydroxyurea treatment. Like its fission yeast counterpart, human Cds1 phosphorylated Cdc25C to promote the binding of 14-3-3 proteins. These findings suggest that the checkpoint function of HuCds1 is conserved in yeast and mammals.

Brefeldin A-inhibited guanine nucleotide-exchange activity of Sec7 domain from yeast Sec7 with yeast and mammalian ADP ribosylation factors

The Saccharomyces cerevisiae Sec7 protein (ySec7p), which is an important component of the yeast secretory pathway, contains a sequence of ≈200 amino acids referred to as a Sec7 domain. Similar Sec7 domain sequences have been recognized in several guanine nucleotide-exchange proteins (GEPs) for ADP ribosylation factors (ARFs). ARFs are ≈20-kDa GTPases that regulate intracellular vesicular membrane trafficking and activate phospholipase D. GEPs activate ARFs by catalyzing the replacement of bound GDP with GTP. We, therefore, undertook to determine whether a Sec7 domain itself could catalyze nucleotide exchange on ARF and found that it exhibited brefeldin A (BFA)-inhibitable ARF GEP activity. BFA is known to inhibit ARF GEP activity in Golgi membranes, thereby causing reversible apparent dissolution of the Golgi complex in many cells. The His6-tagged Sec7 domain from ySec7p (rySec7d) synthesized in Escherichia coli enhanced binding of guanosine 5′-[γ-[35S]thio]triphosphate by recombinant yeast ARF1 (ryARF1) and ryARF2 but not by ryARF3. The effects of rySec7d on ryARF2 were inhibited by BFA in a concentration-dependent manner but not by inactive analogues of BFA (B-17, B-27, and B-36). rySec7d also promoted BFA-sensitive guanosine 5′-[γ-thio]triphosphate binding by nonmyristoylated recombinant human ARF1 (rhARF1), rhARF5, and rhARF6, although the effect on rhARF6 was very small. These results are consistent with the conclusion that the yeast Sec7 domain itself contains the elements necessary for ARF GEP activity and its inhibition by BFA.

A single-headed dimer of Escherichia coli ribosomal protein L7/L12 supports protein synthesis

During protein synthesis, the two elongation factors Tu and G alternately bind to the 50S ribosomal subunit at a site of which the protein L7/L12 is an essential component. L7/L12 is present in each 50S subunit in four copies organized as two dimers. Each dimer consists of distinct domains: a single N-terminal (“tail”) domain that is responsible for both dimerization and binding to the ribosome via interaction with the protein L10 and two independent globular C-terminal domains (“heads”) that are required for binding of elongation factors to ribosomes. The two heads are connected by flexible hinge sequences to the N-terminal domain. Important questions concerning the mechanism by which L7/L12 interacts with elongation factors are posed by us in response to the presence of two dimers, two heads per dimer, and their dynamic, mobile properties. In an attempt to answer these questions, we constructed a single-headed dimer of L7/L12 by using recombinant DNA techniques and chemical cross-linking. This chimeric molecule was added to inactive core particles lacking wild-type L7/L12 and shown to restore activity to a level approaching that of wild-type two-headed L7/L12.

Molecular coevolution within a Drosophila clock gene

The period (per) gene in Drosophila melanogaster provides an integral component of biological rhythmicity and encodes a protein that includes a repetitive threonine-glycine (Thr-Gly) tract. Similar repeats are found in the frq and wc2 clock genes of Neurospora crassa and in the mammalian per homologues, but their circadian functions are unknown. In Drosophilids, the length of the Thr-Gly repeat varies widely between species, and sequence comparisons have suggested that the repeat length coevolves with the immediately flanking amino acids. A functional test of the coevolution hypothesis was performed by generating several hybrid per transgenes between Drosophila pseudoobscura and D. melanogaster, whose repetitive regions differ in length by about 150 amino acids. The positions of the chimeric junctions were slightly altered in each transgene. Transformants carrying per constructs in which the repeat of one species was juxtaposed next to the flanking region of the other were almost arrhythmic or showed a striking temperature sensitivity of the circadian period. In contrast, transgenes in which the repeat and flanking regions were conspecific gave wild-type levels of circadian rescue. These results support the coevolutionary interpretation of the interspecific sequence changes in this region of the PER molecule and reveal a functional dimension to this process related to the clock’s temperature compensation.

Resistance gene N-mediated de novo synthesis and activation of a tobacco mitogen-activated protein kinase by tobacco mosaic virus infection

Salicylic acid-induced protein kinase (SIPK) and wounding-induced protein kinase (WIPK), two distinct members of the mitogen-activated protein (MAP) kinase family, are activated in tobacco resisting infection by tobacco mosaic virus (TMV). WIPK activation by TMV depends on the disease-resistance gene N because infection of susceptible tobacco not carrying the N gene failed to activate WIPK. Activation of WIPK required not only posttranslational phosphorylation but also a preceding rise in its mRNA and de novo synthesis of WIPK protein. The induction by TMV of WIPK mRNA and protein also occurred systemically. Its activation at the mRNA, protein, and enzyme levels was independent of salicylic acid. The regulation of WIPK at multiple levels by an N gene-mediated signal(s) suggests that this MAP kinase may be an important component upstream of salicylic acid in the signal-transduction pathway(s) leading to local and systemic resistance to TMV.

Dissociation of cytokine-induced phosphorylation of Bad and activation of PKB/akt: Involvement of MEK upstream of Bad phosphorylation

The phosphatidylinositol 3-kinase (PI3K)-signaling pathway has emerged as an important component of cytokine-mediated survival of hemopoietic cells. Recently, the protein kinase PKB/akt (referred to here as PKB) has been identified as a downstream target of PI3K necessary for survival. PKB has also been implicated in the phosphorylation of Bad, potentially linking the survival effects of cytokines with the Bcl-2 family. We have shown that granulocyte/macrophage colony-stimulating factor (GM-CSF) maintains survival in the absence of PI3K activity, and we now show that when PKB activation is also completely blocked, GM-CSF is still able to stimulate phosphorylation of Bad. Interleukin 3 (IL-3), on the other hand, requires PI3K for survival, and blocking PI3K partially inhibited Bad phosphorylation. IL-4, unique among the cytokines in that it lacks the ability to activate the p21ras–mitogen-activated protein kinase (MAPK) cascade, was found to activate PKB and promote cell survival, but it did not stimulate Bad phosphorylation. Finally, although our data suggest that the MAPK pathway is not required for inhibition of apoptosis, we provide evidence that phosphorylation of Bad may be occurring via a MAPK/ERK kinase (MEK)-dependent pathway. Together, these results demonstrate that although PI3K may contribute to phosphorylation of Bad in some instances, there is at least one other PI3K-independent pathway involved, possibly via activation of MEK. Our data also suggest that although phosphorylation of Bad may be one means by which cytokines can inhibit apoptosis, it may be neither sufficient nor necessary for the survival effect.

Epithelial antibiotic induced in states of disease

Epithelial defensins provide an active defense against the external microbial environment. We investigated the distribution and expression of this class of antimicrobial peptides in normal cattle and in animals in varying states of disease. β-defensin mRNA was found to be widely expressed in numerous exposed epithelia but was found at higher levels in tissues that are constantly exposed to and colonized by microorganisms. We observed induction in ileal mucosa during chronic infection with Mycobacterium paratuberculosis and in bronchial epithelium after acute infection with Pasteurella haemolytica. It has been proposed that expression of antimicrobial peptides is an integral component of the inflammatory response. The results reported here support this hypothesis and suggest that epithelial defensins provide a rapidly mobilized local defense against infectious organisms.

Dictyostelium myosin II null mutant can still cap Con A receptors

Cross-linked antigens on the surface of a motile cell cap at the trailing end of the cell. In Dictyostelium discoideum, myosin II null mutants have previously been reported to be unable to cap Con A receptors, although they are able to locomote. This finding implicated myosin II as an essential component of the capping mechanism, although not of the machinery for locomotion. Here we show that myosin II null mutants do cap Con A receptors, albeit less efficiently than does wild type. This shows that cap formation is not absolutely dependent on myosin II and that a close mechanistic relationship between capping, particle movement, and cell migration may still exist.