Multimodal integration of functional and structural brain connectivity. An application to the characterization of Mild Cognitive Impairment

La investigación para el conocimiento del cerebro es una ciencia joven, su inicio se remonta a Santiago Ramón y Cajal en 1888. Desde esta fecha a nuestro tiempo la neurociencia ha avanzado mucho en el desarrollo de técnicas que permiten su estudio. Desde la neurociencia cognitiva hoy se explican muchos modelos que nos permiten acercar a nuestro entendimiento a capacidades cognitivas complejas. Aun así hablamos de una ciencia casi en pañales que tiene un lago recorrido por delante. Una de las claves del éxito en los estudios de la función cerebral ha sido convertirse en una disciplina que combina conocimientos de diversas áreas: de la física, de las matemáticas, de la estadística y de la psicología. Esta es la razón por la que a lo largo de este trabajo se entremezclan conceptos de diferentes campos con el objetivo de avanzar en el conocimiento de un tema tan complejo como el que nos ocupa: el entendimiento de la mente humana. Concretamente, esta tesis ha estado dirigida a la integración multimodal de la magnetoencefalografía (MEG) y la resonancia magnética ponderada en difusión (dMRI). Estas técnicas son sensibles, respectivamente, a los campos magnéticos emitidos por las corrientes neuronales, y a la microestructura de la materia blanca cerebral. A lo largo de este trabajo hemos visto que la combinación de estas técnicas permiten descubrir sinergias estructurofuncionales en el procesamiento de la información en el cerebro sano y en el curso de patologías neurológicas. Más específicamente en este trabajo se ha estudiado la relación entre la conectividad funcional y estructural y en cómo fusionarlas. Para ello, se ha cuantificado la conectividad funcional mediante el estudio de la sincronización de fase o la correlación de amplitudes entre series temporales, de esta forma se ha conseguido un índice que mide la similitud entre grupos neuronales o regiones cerebrales. Adicionalmente, la cuantificación de la conectividad estructural a partir de imágenes de resonancia magnética ponderadas en difusión, ha permitido hallar índices de la integridad de materia blanca o de la fuerza de las conexiones estructurales entre regiones. Estas medidas fueron combinadas en los capítulos 3, 4 y 5 de este trabajo siguiendo tres aproximaciones que iban desde el nivel más bajo al más alto de integración. Finalmente se utilizó la información fusionada de MEG y dMRI para la caracterización de grupos de sujetos con deterioro cognitivo leve, la detección de esta patología resulta relevante en la identificación precoz de la enfermedad de Alzheimer. Esta tesis está dividida en seis capítulos. En el capítulos 1 se establece un contexto para la introducción de la connectómica dentro de los campos de la neuroimagen y la neurociencia. Posteriormente en este capítulo se describen los objetivos de la tesis, y los objetivos específicos de cada una de las publicaciones científicas que resultaron de este trabajo. En el capítulo 2 se describen los métodos para cada técnica que fue empleada: conectividad estructural, conectividad funcional en resting state, redes cerebrales complejas y teoría de grafos y finalmente se describe la condición de deterioro cognitivo leve y el estado actual en la búsqueda de nuevos biomarcadores diagnósticos. En los capítulos 3, 4 y 5 se han incluido los artículos científicos que fueron producidos a lo largo de esta tesis. Estos han sido incluidos en el formato de la revista en que fueron publicados, estando divididos en introducción, materiales y métodos, resultados y discusión. Todos los métodos que fueron empleados en los artículos están descritos en el capítulo 2 de la tesis. Finalmente, en el capítulo 6 se concluyen los resultados generales de la tesis y se discuten de forma específica los resultados de cada artículo. ABSTRACT In this thesis I apply concepts from mathematics, physics and statistics to the neurosciences. This field benefits from the collaborative work of multidisciplinary teams where physicians, psychologists, engineers and other specialists fight for a common well: the understanding of the brain. Research on this field is still in its early years, being its birth attributed to the neuronal theory of Santiago Ramo´n y Cajal in 1888. In more than one hundred years only a very little percentage of the brain functioning has been discovered, and still much more needs to be explored. Isolated techniques aim at unraveling the system that supports our cognition, nevertheless in order to provide solid evidence in such a field multimodal techniques have arisen, with them we will be able to improve current knowledge about human cognition. Here we focus on the multimodal integration of magnetoencephalography (MEG) and diffusion weighted magnetic resonance imaging. These techniques are sensitive to the magnetic fields emitted by the neuronal currents and to the white matter microstructure, respectively. The combination of such techniques could bring up evidences about structural-functional synergies in the brain information processing and which part of this synergy fails in specific neurological pathologies. In particular, we are interested in the relationship between functional and structural connectivity, and how two integrate this information. We quantify the functional connectivity by studying the phase synchronization or the amplitude correlation between time series obtained by MEG, and so we get an index indicating similarity between neuronal entities, i.e. brain regions. In addition we quantify structural connectivity by performing diffusion tensor estimation from the diffusion weighted images, thus obtaining an indicator of the integrity of the white matter or, if preferred, the strength of the structural connections between regions. These quantifications are then combined following three different approaches, from the lowest to the highest level of integration, in chapters 3, 4 and 5. We finally apply the fused information to the characterization or prediction of mild cognitive impairment, a clinical entity which is considered as an early step in the continuum pathological process of dementia. The dissertation is divided in six chapters. In chapter 1 I introduce connectomics within the fields of neuroimaging and neuroscience. Later in this chapter we describe the objectives of this thesis, and the specific objectives of each of the scientific publications that were produced as result of this work. In chapter 2 I describe the methods for each of the techniques that were employed, namely structural connectivity, resting state functional connectivity, complex brain networks and graph theory, and finally, I describe the clinical condition of mild cognitive impairment and the current state of the art in the search for early biomarkers. In chapters 3, 4 and 5 I have included the scientific publications that were generated along this work. They have been included in in their original format and they contain introduction, materials and methods, results and discussion. All methods that were employed in these papers have been described in chapter 2. Finally, in chapter 6 I summarize all the results from this thesis, both locally for each of the scientific publications and globally for the whole work.

Improving Crop Models: Incorporating New Processes, New Approaches, and Better Calibrations

Early ancestors of crop simulation models (De Wit, 1965; Monteith, 1965; Duncan et al., 1967) were born before primitive personal computers were available (e.g. Apple II released in 1977, IBM PC released in 1981). Paleo-computer programs were run in mainframes with the support of punch cards. As computers became more available and powerful, crop models evolved into sophisticated tools summarizing our understanding of how crops operate. This evolution was triggered by the need to answer new scientific questions and improve the accuracy of model simulations, especially under limiting conditions.

Paisaje de energías: conocimiento estético en el enfoque ambiental del proyecto

Desde hace ya varias décadas la praxis de la ecología ha venido reconociendo la necesidad de estudiar los múltiples sistemas de interacción del ser humano, como especie viva, y su entorno. Entidades espaciales como el paisaje geográfico son empleadas para delimitar sistemas territoriales operados por la sociedad, precisando campos concretos de su acción física, biológica y cultural. La ecología aborda así el conocimiento científico del territorio como asentamiento humano, rastrea sus patrones espaciales y analiza su compleja estructura funcional. En ese contexto, la transferencia de herramientas e instrumentos desde la ecología al ámbito proyectivo posee ya un bagaje de más de cinco décadas. Cada vez con más frecuencia el proyecto emplea parámetros, inventarios, fórmulas, indicadores y tecnologías que tratan de dar una respuesta ambientalmente adecuada a los condicionantes de contorno, por ejemplo aprovechando las condiciones climáticas en la optimización energética o proponiendo programas de usos del suelo que eviten perturbaciones en ecosistemas de interés. Con todo, en el momento presente surgen voces que, ante el dominio indiscutible de los enfoques netamente deterministas, tratan de recordar que los principios del pensamiento ecológico van más allá del mero control cuantitativo de los procesos biofísicos. Recuerdan que la etología demostró a principios del XX que el ser humano, como ser consciente, inviste una relación de intimidad con su entorno que supera tales perspectivas: a través de la correspondencia entre percepción y significación, entre lo físico y lo psíquico, entre interioridad y exterioridad, las personas abrazan la plenitud de aquello que les rodea en un acto de profunda conciliación afectiva. De tal ligadura de intimidad depende, sí o sí, y en toda su profundidad, la aceptación humana del entorno construido. A través de la noción de ambiente [Umwelt] se demuestra que la relación del hombre con su entorno es inseparable, bidireccional y coordinada y, por lo tanto, desde una posición coherente, la experiencia del espacio puede ser examinada a partir de la reciprocidad que constituyen, en continuidad, la persona y el lugar. De esta forma, la tesis dirige su objetivo principal a explorar y considerar, desde el proyecto, el significado y la influencia de la experiencia ambiental del espacio construido en la vida humana. Es más que probable que buena parte de los problemas de desafección del hombre con los paisajes transformados de su contemporaneidad tenga que ver con que tanto las intensidades de la experiencia y percepción humana, como la potestad interpretativa de sus productos culturales, incluyendo la arquitectura, han sido fuertemente reducidas. Ante este problema, la investigación toma como hipótesis la oportunidad que ofrece el pensamiento ecológico de reformular la experiencia estética como un acto de conocimiento, como un evento donde se da el encuentro físico y se construyen significados, donde se sancionan valores sociales y se mira hacia el futuro. Se ha de señalar que la presente tesis doctoral arranca en el Laboratorio de Paisaje del Grupo de Investigación Paisaje Cultural de la Universidad Politécnica de Madrid dirigido por Concha Lapayese y Darío Gazapo, y por tanto hace suyos para el estado del arte los principales conceptos e ideas bajo los que el trabajo teórico y práctico del grupo se viene orientando desde hace años: la consideración del paisaje como acontecimiento; la oscilación de la interpretación entre un paisaje específico y un paisaje genérico en un mundo globalizado; el reconocimiento de la experiencia estética del paisaje como una toma de conciencia social; y en definitiva, la reivindicación de la interioridad en el proyecto contemporáneo. La investigación profundiza en una línea de oportunidad que se abre al promover lo que se ha llamado un conocimiento por lo sentido como estrategia ambiental que permite contrarrestar mitos profundamente arraigados en las estructuras sociales. El primer paso en ese recorrido sería explorar ecológicamente el aporte de la experiencia estética; esto es, su consideración como forma de conocimiento específico. Resultaría pertinente impulsar la idea de la inmersión en el paisaje como fenómeno experiencial, sensual y corporal, y enfrentar, desde ahí, el problema de la aceptación social de lo nuevo y lo trasformado de acuerdo con el momento actual. La exploración sobre la afectividad en el ambiente no es, en cualquier caso, un asunto nuevo. Sin pretensiones de historiografía, dos momentos del siglo XX concentran el interés de la investigación. La primera se corresponde fundamentalmente con la segunda década del siglo, en relación a una serie de influencias que desde los avances científicos determinaron singulares aventuras del arte más experimental. La segunda se posiciona en el entorno de 1970, época en la que es conocido el interés que despertaron las cuestiones ambientales. En ambos casos se han estudiado aportaciones que desvelan conceptos determinantes en la definición de la experiencia estética como un evento de adquisición de conocimiento por lo sentido. Es conveniente adelantar el rol de centralidad que para la investigación tiene el concepto de energía, tal como el propio título subraya. La energía como realidad material y sensible es el sustrato que permite navegar por el principio de unidad epistemológica que subyace al pensamiento ecológico. Sus continuas referencias simbólicas, físicas y metafóricas entre los artistas estudiados no son un mero recurso iconográfico: mantienen inherente el principio de continuidad ambiental en el cual el ser humano y la inmensidad del cosmos navegan indisociables. Un discurso unificado y consistente sobre los aportes de la experiencia estética enfocada como forma de conocimiento por lo sentido hila la lectura histórica, conceptual y práctica de toda la investigación. Con ello se alcanza a hilvanar un diagrama conceptual, modelo de análisis proyectivo, que recoge ideas científicas, filosóficas y proyectivas. De alguna manera, el diagrama trata de dibujar, desde los principios del pensamiento ecológico, la correlación de continuidad que, vacilante, tensa, sutil y frágil se desplaza incesante e irresuelta entre interioridad y exterioridad. ABSTRACT Over the last few decades ecological practice has come to acknowledge a need for studying the multiple systems of interaction between the human being - inasmuch as it is a living species - and its environment. Spatial entities such as the geographic notion of landscape have been used to delimitate the territorial systems operated by society and to describe in detail specific fields of its physical, biological and cultural action. Ecology has thus managed to address the scientific knowledge of the territory as a human settlement, tracking its spatial patterns and analysing its complex functional structure. In this context, the transfer of tools and instruments from the field of ecology to that of design has a tradition already going back more than fifty years. Increasingly more often, design makes use of parameters, inventories, formulas, indicators and technologies to give an environmentally sound response to contour conditions: for instance, taking advantage of the local climate for the optimisation of energy consumption or proposing land uses that avoid disturbing valuable ecosystems. Yet in the present day some voices have arisen that, against the uncontested domination of purely positivistic approaches, are trying to draw attention to the fact that the principles of ecological thought go beyond mere quantitative control of biophysical processes. They point out that, in the early 20th century, ethology proved that the human being, as a conscious entity, invests itself into a relationship of intimacy with its environment that surpasses such perspectives: through the correspondences between perception and signification, between physical and psychological or between inside and outside, people embrace the entirety of their surroundings in an action of deep affective conciliation. It is on this link of intimacy that - fully and unquestionably - human acceptance of the built environment depends. Through the notion of environment [Umwelt] it can be proven that the relationship between the human being and its environment is inseparable, bidirectional and coordinated; and that, therefore, from a coherent position the experience of space can be examined through the reciprocity constituted continuously by person and place. Thus, the main goal in this thesis is to explore and acknowledge, from the standpoint of design, the meaning and influence of the environmental experience in human life. It is extremely likely that many of the issues with mankind’s alienation from the transformed landscapes of the present day arise from the fact that both the intensity of human perception and experience and the interpretive capacity of its cultural products –including architecture - have been greatly reduced. Facing this issue, research has taken as hypothesis the opportunity offered by ecological thought of reformulating aesthetic experience as an act of knowledge – as an event where physical encounter takes place and meanings are constructed; where social values are sanctioned and the path towards the future is drawn. This notwithstanding, the present thesis began in the Landscape Laboratory of the Technical University of Madrid Cultural Landscape Research Group (GIPC-UPM), led by Concha Lapayese and Darío Gazapo; and has therefore appropriated for its state of the art the main concepts and ideas that have been orienting the practical and theoretical work of the latter: the understanding of landscape as an event, the oscillation of interpretation between a specific and a generic landscape within a globalised world; the acknowledgement of the aesthetic experience of landscape as a way of acquiring social awareness; and, all in all, a vindication of interiority in contemporary design. An exploration has been made of the line of opportunity that is opened when promoting what has been termed knowledge through the senses as an environmental strategy allowing to counter myths deeply rooted in social structures. The first step in this path would be an ecological exploration of the contribution of the aesthetic experience; that is, its consideration as a type of specific knowledge. It would be pertinent to further the idea of immersion into the landscape as an experiential, sensual and corporeal phenomenon and, from that point, to face the issue of social acceptance of what is new and transformed according to the values of the present day. The exploration of affectivity in the environment is not, at any rate, a new topic. Without aspiring to make a history of it, we can mark two points in the 20th century that have concentrated the interest of this research. The first coincides with the second decade of the century and relates to a number of influences that, arising from scientific progress, determined the singular adventures of the more experimental tendencies in art. The second is centred around 1970: a period in which the interest drawn by environmental matters is well known. In both cases, contributions have been studied that reveal crucial concepts in defining the aesthetic experience as an event for the acquisition of knowledge through the senses. It is necessary to highlight the role of centrality that the concept of energy has throughout this research, as is evident even in its title. Energy as a material, sensitive reality is the substrate making it possible to navigate through the principle of epistemological unity underlying ecological thought. The continuous symbolic, physical and metaphorical references to it among the artists studied here are not a mere iconographic source: they remind of the inherency of the principle of environmental continuity within which the human being and the immensity of cosmos travel indissociably. A unified, consistent discourse on the contributions of the aesthetic experience addressed as knowledge through the senses weaves together the historic, conceptual and practical reading of the whole research. With it, a conceptual diagram is constructed – a model of design analysis – gathering together scientific, philosophical and design ideas. Somehow, the diagram tries to draw from the principles of ecological thought the correlation of continuity that, vacillating, tense, subtle and fragile, shifts incessantly and unresolved between interiority and exteriority.

Mining Abstractions in Scientific Workows

Los flujos de trabajo científicos han sido adoptados durante la última década para representar los métodos computacionales utilizados en experimentos in silico, así como para dar soporte a sus publicaciones asociadas. Dichos flujos de trabajo han demostrado ser útiles para compartir y reproducir experimentos científicos, permitiendo a investigadores visualizar, depurar y ahorrar tiempo a la hora de re-ejecutar un trabajo realizado con anterioridad. Sin embargo, los flujos de trabajo científicos pueden ser en ocasiones difíciles de entender y reutilizar. Esto es debido a impedimentos como el gran número de flujos de trabajo existentes en repositorios, su heterogeneidad o la falta generalizada de documentación y ejemplos de uso. Además, dado que normalmente es posible implementar un mismo método utilizando algoritmos o técnicas distintas, flujos de trabajo aparentemente distintos pueden estar relacionados a un determinado nivel de abstracción, basándose, por ejemplo, en su funcionalidad común. Esta tesis se centra en la reutilización de flujos de trabajo y su abstracción mediante la exploración de relaciones entre los flujos de trabajo de un repositorio y la extracción de abstracciones que podrían ayudar a la hora de reutilizar otros flujos de trabajo existentes. Para ello, se propone un modelo simple de representación de flujos de trabajo y sus ejecuciones, se analizan las abstracciones típicas que se pueden encontrar en los repositorios de flujos de trabajo, se exploran las prácticas habituales de los usuarios a la hora de reutilizar flujos de trabajo existentes y se describe un método para descubrir abstracciones útiles para usuarios, basadas en técnicas existentes de teoría de grafos. Los resultados obtenidos exponen las abstracciones y prácticas comunes de usuarios en términos de reutilización de flujos de trabajo, y muestran cómo las abstracciones que se extraen automáticamente tienen potencial para ser reutilizadas por usuarios que buscan diseñar nuevos flujos de trabajo. Abstract Scientific workflows have been adopted in the last decade to represent the computational methods used in in silico scientific experiments and their associated research products. Scientific workflows have demonstrated to be useful for sharing and reproducing scientific experiments, allowing scientists to visualize, debug and save time when re-executing previous work. However, scientific workflows may be difficult to understand and reuse. The large amount of available workflows in repositories, together with their heterogeneity and lack of documentation and usage examples may become an obstacle for a scientist aiming to reuse the work from other scientists. Furthermore, given that it is often possible to implement a method using different algorithms or techniques, seemingly disparate workflows may be related at a higher level of abstraction, based on their common functionality. In this thesis we address the issue of reusability and abstraction by exploring how workflows relate to one another in a workflow repository, mining abstractions that may be helpful for workflow reuse. In order to do so, we propose a simple model for representing and relating workflows and their executions, we analyze the typical common abstractions that can be found in workflow repositories, we explore the current practices of users regarding workflow reuse and we describe a method for discovering useful abstractions for workflows based on existing graph mining techniques. Our results expose the common abstractions and practices of users in terms of workflow reuse, and show how our proposed abstractions have potential to become useful for users designing new workflows.

Conservation of Computational Scientific Execution Environments for Workflow-based Experiments Using Ontologies

La reproducibilidad de estudios y resultados científicos es una meta a tener en cuenta por cualquier científico a la hora de publicar el producto de una investigación. El auge de la ciencia computacional, como una forma de llevar a cabo estudios empíricos haciendo uso de modelos matemáticos y simulaciones, ha derivado en una serie de nuevos retos con respecto a la reproducibilidad de dichos experimentos. La adopción de los flujos de trabajo como método para especificar el procedimiento científico de estos experimentos, así como las iniciativas orientadas a la conservación de los datos experimentales desarrolladas en las últimas décadas, han solucionado parcialmente este problema. Sin embargo, para afrontarlo de forma completa, la conservación y reproducibilidad del equipamiento computacional asociado a los flujos de trabajo científicos deben ser tenidas en cuenta. La amplia gama de recursos hardware y software necesarios para ejecutar un flujo de trabajo científico hace que sea necesario aportar una descripción completa detallando que recursos son necesarios y como estos deben de ser configurados. En esta tesis abordamos la reproducibilidad de los entornos de ejecución para flujos de trabajo científicos, mediante su documentación usando un modelo formal que puede ser usado para obtener un entorno equivalente. Para ello, se ha propuesto un conjunto de modelos para representar y relacionar los conceptos relevantes de dichos entornos, así como un conjunto de herramientas que hacen uso de dichos módulos para generar una descripción de la infraestructura, y un algoritmo capaz de generar una nueva especificación de entorno de ejecución a partir de dicha descripción, la cual puede ser usada para recrearlo usando técnicas de virtualización. Estas contribuciones han sido aplicadas a un conjunto representativo de experimentos científicos pertenecientes a diferentes dominios de la ciencia, exponiendo cada uno de ellos diferentes requisitos hardware y software. Los resultados obtenidos muestran la viabilidad de propuesta desarrollada, reproduciendo de forma satisfactoria los experimentos estudiados en diferentes entornos de virtualización. ABSTRACT Reproducibility of scientific studies and results is a goal that every scientist must pursuit when announcing research outcomes. The rise of computational science, as a way of conducting empirical studies by using mathematical models and simulations, have opened a new range of challenges in this context. The adoption of workflows as a way of detailing the scientific procedure of these experiments, along with the experimental data conservation initiatives that have been undertaken during last decades, have partially eased this problem. However, in order to fully address it, the conservation and reproducibility of the computational equipment related to them must be also considered. The wide range of software and hardware resources required to execute a scientific workflow implies that a comprehensive description detailing what those resources are and how they are arranged is necessary. In this thesis we address the issue of reproducibility of execution environments for scientific workflows, by documenting them in a formalized way, which can be later used to obtain and equivalent one. In order to do so, we propose a set of semantic models for representing and relating the relevant information of those environments, as well as a set of tools that uses these models for generating a description of the infrastructure, and an algorithmic process that consumes these descriptions for deriving a new execution environment specification, which can be enacted into a new equivalent one using virtualization solutions. We apply these three contributions to a set of representative scientific experiments, belonging to different scientific domains, and exposing different software and hardware requirements. The obtained results prove the feasibility of the proposed approach, by successfully reproducing the target experiments under different virtualization environments.

Networked Utopia : the Architecture and Urbanism of the Bata Shoe Company Satellite Cities = Utopia en red : arquitectura y urbanismo en las ciudades satélite de la Bata Shoe Company, 1930 al presente

From its humble beginnings as a small workshop established by Tomáš Baťa in 1874, the Bata Shoe Company became a gigantic concern in the 1920s, built on the principles of scientific management and welfare capitalism. The growth of the company engulfed Zlín (in today’s Czech Republic), its hometown, and transformed it into a modern industrial garden city satisfying the needs of both a growing industrial population, and those of the company itself. As a reaction to the aftermath of the crisis of 1929, the enterprise began a strategy of decentralization and international expansion characterized by the design and construction of a series of modern industrial towns that replicated the model of Zlín around the globe. This study is an exhaustive survey of these cities, their rationale, design, and their postindustrial conditions; it is a comparative work that has used field trips, photography, interviews, and archival material to explain the logics behind Bata’s project, to document the design and implementation of the model to multiple contexts and geographies, and to evaluate of the urban legacy of this undertaking. Finally, the research explores the question of what can the design disciplines, and other parties involved, learn from a full synthesis on the history and urbanism of the Bata satellite cities with regard to the re-imagination and sustainability of contemporary industry-sponsored interventions in developing geographies. RESUMEN Con origen en un humilde y pequeño taller fundado en 1874 por Tomáš Baťa, la Bata Shoe Company creció hasta convertirse en una gigantesca empresa en los anos 20, fundada en principios de control científico de la producción y capitalismo de bienestar. El crecimiento de la compañía se extendió por Zlín (en la actual República Checa), su pueblo de nacimiento, y la transformó en una moderna ciudad jardín industrial capaz de satisfacer las necesidades tanto de una población en alza como de la propia empresa. Como reacción a la crisis de 1929, Bata inició una estrategia de descentralización y expansión internacional caracterizada por el proyecto y construcción de modernas ciudades industriales que replicaron el modelo de Zlín por el mundo. Esta tesis es un estudio exhaustivo de estas ciudades: las razones detrás del proyecto, su diseño, y su condición post-industrial; es un estudio comparativo que se ha servido de trabajo de campo, documentación fotográfica, entrevistas y materiales de archivo para explicar la lógica detrás del proyecto de Bata, documentar el diseño e implementación de tal modelo en múltiples contextos y geografías, y valorar el legado urbano de esta empresa. Finalmente, la investigación evalúa qué podrían aprender las disciplinas del diseño y otras partes implicadas de una síntesis completa de la historia y el urbanismo de las ciudades satélite de Bata, en lo relativo a la reinvención y sostenibilidad de proyectos contemporáneos de la industria en geografías en desarrollo.

Estudo das potencialidades do trabalho prático de orientação investigativa no 1º ciclo do ensino básico

Este estudo insere-se num relatório de estágio, referente ao grau de Mestre em Educação Pré-Escolar e Ensino do 1.º Ciclo do Ensino Básico, e baseia-se numa problemática assente na análise das potencialidades do trabalho prático de orientação investigativa (TPOI). Tratase de uma pesquisa na prática profissional desenvolvida em contexto de estágio, em duas escolas do 1.º CEB do Concelho de Santarém, que teve ainda como objetivo compreender as dificuldades que se colocam durante a planificação e implementação de atividades POI. Para o efeito, utilizaram-se diferentes instrumentos de recolha de dados: observação, entrevistas e documentos escritos. Ao longo do processo de planificação/implementação/reflexão foram identificadas as principais dificuldades sentidas pela futura educadora/professora nomeadamente a preparação dos guiões e do material, a gestão da turma e as dificuldades dos alunos. Os resultados demonstraram inúmeras potencialidades do TPOI na promoção de aprendizagens ao nível dos conteúdos científicos abordados, dos processos científicos e do trabalho de grupo. Contudo, os resultados permitiram também constatar que um grau de abertura elevado das atividades nem sempre apresenta o efeito desejável nas aprendizagens dos alunos, verificando-se que as características dos alunos e uma maior familiarização com este tipo de atividade é condição essencial para promover a autonomia.

The effect of flow speed and food size on the capture efficiency and feeding behaviour of the cold-water coral Lophelia pertusa

Acknowledgements The authors acknowledge L. Wicks and B. de Francisco for helping in coral sampling and coral care in the aquaria facilities at SAMS. Thanks to C. Campbell and the CCAP for kind support and help. Scientific party and crew on board the RVs Calanus and Seol Mara, as well as on board the RRS James Cook during the Changing Oceans cruise (JC_073) are greatly acknowledged. Thanks to colleagues at SAMS for their support during our stay at SAMS. We are in debt with A. Olariaga for his help modifying the cylindrical experimental chambers used in the experiments, and C.C. Suckling for assistance with the flume experiment. Many thanks go to G. Kazadinis for preparing the POM used in the feeding experiments. We also thank two anonymous reviewers and the editor for their constructive comments, which contribute to improve the manuscript. This work has been supported by the European Commission through two ASSEMBLE projects (grant agreement no. 227799) conducted in 2010 and 2011 at SAMS, as well as by the UK Ocean Acidification Research Programme's Benthic Consortium project (awards NE/H01747X/1 and NE/H017305/1) funded by NERC. [SS]

Neuroimaging of cerebral activations and deactivations associated with hypercapnia and hunger for air

There are defined medullary, mesencephalic, hypothalamic, and thalamic functions in regulation of respiration, but knowledge of cortical control and the elements subserving the consciousness of breathlessness and air hunger is limited. In nine young adults, air hunger was produced acutely by CO2 inhalation. Comparisons were made with inhalation of a N2/O2 gas mixture with the same apparatus, and also with paced breathing, and with eyes closed rest. A network of activations in pons, midbrain (mesencephalic tegmentum, parabrachial nucleus, and periaqueductal gray), hypothalamus, limbic and paralimbic areas (amygdala and periamygdalar region) cingulate, parahippocampal and fusiform gyrus, and anterior insula were seen along with caudate nuclei and pulvinar activations. Strong deactivations were seen in dorsal cingulate, posterior cingulate, and prefrontal cortex. The striking response of limbic and paralimbic regions points to these structures having a singular role in the affective sequelae entrained by disturbance of basic respiratory control whereby a process of which we are normally unaware becomes a salient element of consciousness. These activations and deactivations include phylogenetically ancient areas of allocortex and transitional cortex that together with the amygdalar/periamygdalar region may subserve functions of emotional representation and regulation of breathing.

RECODE: a database of frameshifting, bypassing and codon redefinition utilized for gene expression

The RECODE database is a compilation of ‘programmed’ translational recoding events taken from the scientific literature and personal communications. The database deals with programmed ribosomal frameshifting, codon redefinition and translational bypass occurring in a variety of organisms. The entries for each event include the sequences of the corresponding genes, their encoded proteins for both the normal and alternate decoding, the types of the recoding events involved, trans-factors and cis-elements that influence recoding. The database is freely available at http://recode.genetics.utah.edu/.

Arabidopsis Sec21p and Sec23p Homologs. Probable Coat Proteins of Plant COP-Coated Vesicles1

Intracellular protein transport between the endoplasmic reticulum (ER) and the Golgi apparatus and within the Golgi apparatus is facilitated by COP (coat protein)-coated vesicles. Their existence in plant cells has not yet been demonstrated, although the GTP-binding proteins required for coat formation have been identified. We have generated antisera against glutathione-S-transferase-fusion proteins prepared with cDNAs encoding the Arabidopsis Sec21p and Sec23p homologs (AtSec21p and AtSec23p, respectively). The former is a constituent of the COPI vesicle coatomer, and the latter is part of the Sec23/24p dimeric complex of the COPII vesicle coat. Cauliflower (Brassica oleracea) inflorescence homogenates were probed with these antibodies and demonstrated the presence of AtSec21p and AtSec23p antigens in both the cytosol and membrane fractions of the cell. The membrane-associated forms of both antigens can be solubilized by treatments typical for extrinsic proteins. The amounts of the cytosolic antigens relative to the membrane-bound forms increase after cold treatment, and the two antigens belong to different protein complexes with molecular sizes comparable to the corresponding nonplant coat proteins. Sucrose-density-gradient centrifugation of microsomal cell membranes from cauliflower suggests that, although AtSec23p seems to be preferentially associated with ER membranes, AtSec21p appears to be bound to both the ER and the Golgi membranes. This could be in agreement with the notion that COPII vesicles are formed at the ER, whereas COPI vesicles can be made by both Golgi and ER membranes. Both AtSec21p and AtSec23p antigens were detected on membranes equilibrating at sucrose densities equivalent to those typical for in vitro-induced COP vesicles from animal and yeast systems. Therefore, a further purification of the putative plant COP vesicles was undertaken.

Quantitative ER ↔ Golgi Transport Kinetics and Protein Separation upon Golgi Exit Revealed by Vesicular Integral Membrane Protein 36 Dynamics in Live CellsV⃞

To quantitatively investigate the trafficking of the transmembrane lectin VIP36 and its relation to cargo-containing transport carriers (TCs), we analyzed a C-terminal fluorescent-protein (FP) fusion, VIP36-SP-FP. When expressed at moderate levels, VIP36-SP-FP localized to the endoplasmic reticulum, Golgi apparatus, and intermediate transport structures, and colocalized with epitope-tagged VIP36. Temperature shift and pharmacological experiments indicated VIP36-SP-FP recycled in the early secretory pathway, exhibiting trafficking representative of a class of transmembrane cargo receptors, including the closely related lectin ERGIC53. VIP36-SP-FP trafficking structures comprised tubules and globular elements, which translocated in a saltatory manner. Simultaneous visualization of anterograde secretory cargo and VIP36-SP-FP indicated that the globular structures were pre-Golgi carriers, and that VIP36-SP-FP segregated from cargo within the Golgi and was not included in post-Golgi TCs. Organelle-specific bleach experiments directly measured the exchange of VIP36-SP-FP between the Golgi and endoplasmic reticulum (ER). Fitting a two-compartment model to the recovery data predicted first order rate constants of 1.22 ± 0.44%/min for ER → Golgi, and 7.68 ± 1.94%/min for Golgi → ER transport, revealing a half-time of 113 ± 70 min for leaving the ER and 1.67 ± 0.45 min for leaving the Golgi, and accounting for the measured steady-state distribution of VIP36-SP-FP (13% Golgi/87% ER). Perturbing transport with AlF4− treatment altered VIP36-SP-GFP distribution and changed the rate constants. The parameters of the model suggest that relatively small differences in the first order rate constants, perhaps manifested in subtle differences in the tendency to enter distinct TCs, result in large differences in the steady-state localization of secretory components.

Think globally, translate locally: What mitotic spindles and neuronal synapses have in common

Early metazoan development is programmed by maternal mRNAs inherited by the egg at the time of fertilization. These mRNAs are not translated en masse at any one time or at any one place, but instead their expression is regulated both temporally and spatially. Recent evidence has shown that one maternal mRNA, cyclin B1, is concentrated on mitotic spindles in the early Xenopus embryo, where its translation is controlled by CPEB (cytoplasmic polyadenylation element binding protein), a sequence-specific RNA binding protein. Disruption of the spindle-associated translation of this mRNA results in a morphologically abnormal mitotic apparatus and inhibited cell division. Mammalian neurons, particularly in the synapto-dendritic compartment, also contain localized mRNAs such as that encoding α-CaMKII. Here, synaptic activation drives local translation, an event that is involved in synaptic plasticity and possibly long-term memory storage. Synaptic translation of α-CaMKII mRNA also appears to be controlled by CPEB, which is enriched in the postsynaptic density. Therefore, CPEB-controlled local translation may influence such seemingly disparate processes as the cell cycle and synaptic plasticity.

Simultaneous optical and X-ray observations of flares and rotational modulation on the RS CVn binary HR 1099 (V711 Tau) from the MUSICOS 1998 campaign

We present simultaneous and continuous observations of the Hα, Hβ, He I D_3, Na I D_1,D_2 doublet and the Ca II H&K lines for the RS CVn system HR 1099. The spectroscopic observations were obtained during the MUSICOS 1998 campaign involving several observatories and instruments, both echelle and long-slit spectrographs. During this campaign, HR 1099 was observed almost continuously for more than 8 orbits of 2^d.8. Two large optical flares were observed, both showing an increase in the emission of Hα, Ca II H K, Hβ and He I D_3 and a strong filling-in of the Na I D_1, D_2 doublet. Contemporary photometric observations were carried out with the robotic telescopes APT-80 of Catania and Phoenix-25 of Fairborn Observatories. Maps of the distribution of the spotted regions on the photosphere of the binary components were derived using the Maximum Entropy and Tikhonov photometric regularization criteria. Rotational modulation was observed in Hα and He I D_3 in anti-correlation with the photometric light curves. Both flares occurred at the same binary phase (0.85), suggesting that these events took place in the same active region. Simultaneous X-ray observations, performed by ASM on board RXTE, show several flare-like events, some of which correlate well with the observed optical flares. Rotational modulation in the X-ray light curve has been detected with minimum flux when the less active G5 V star was in front. A possible periodicity in the X-ray flare-like events was also found.

Sea lions, sacrifice, and ritual : The symbolism of Moche Island imagery

The Mochica, or Moche (c. 100-800 AD) culture, flourished along the northern Peruvian coast. The Moche did not have a formal written language; as such, contemporary scholars base their analysis on Moche iconography and archaeological burial remains. Especially renown for their ceramic artistry, Moche vessels exhibit a wide range of subject matter, including animal and enigmatic figural representations that evoke terrestrial, marine and possibly, spiritual realms. While research has focused on political organization and the interrelationship between sacrifice and warfare, many marine themes have not been fully explored in the discourse. An exploration of sea lion imagery and sacrifice themes suggests that the marine mammals were ritually hunted. A careful iconographic analysis of island scenes demonstrates ritual and gender affiliations held by the Moche about sea lions. In a multi-disciplinary approach, scientific, archaeological and ethnographic resources substantiate this claim.