658 resultados para Suppressible Hyper-aldosteronism


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Los hipergrafos dirigidos se han empleado en problemas relacionados con lógica proposicional, bases de datos relacionales, linguística computacional y aprendizaje automático. Los hipergrafos dirigidos han sido también utilizados como alternativa a los grafos (bipartitos) dirigidos para facilitar el estudio de las interacciones entre componentes de sistemas complejos que no pueden ser fácilmente modelados usando exclusivamente relaciones binarias. En este contexto, este tipo de representación es conocida como hiper-redes. Un hipergrafo dirigido es una generalización de un grafo dirigido especialmente adecuado para la representación de relaciones de muchos a muchos. Mientras que una arista en un grafo dirigido define una relación entre dos de sus nodos, una hiperarista en un hipergrafo dirigido define una relación entre dos conjuntos de sus nodos. La conexión fuerte es una relación de equivalencia que divide el conjunto de nodos de un hipergrafo dirigido en particiones y cada partición define una clase de equivalencia conocida como componente fuertemente conexo. El estudio de los componentes fuertemente conexos de un hipergrafo dirigido puede ayudar a conseguir una mejor comprensión de la estructura de este tipo de hipergrafos cuando su tamaño es considerable. En el caso de grafo dirigidos, existen algoritmos muy eficientes para el cálculo de los componentes fuertemente conexos en grafos de gran tamaño. Gracias a estos algoritmos, se ha podido averiguar que la estructura de la WWW tiene forma de “pajarita”, donde más del 70% del los nodos están distribuidos en tres grandes conjuntos y uno de ellos es un componente fuertemente conexo. Este tipo de estructura ha sido también observada en redes complejas en otras áreas como la biología. Estudios de naturaleza similar no han podido ser realizados en hipergrafos dirigidos porque no existe algoritmos capaces de calcular los componentes fuertemente conexos de este tipo de hipergrafos. En esta tesis doctoral, hemos investigado como calcular los componentes fuertemente conexos de un hipergrafo dirigido. En concreto, hemos desarrollado dos algoritmos para este problema y hemos determinado que son correctos y cuál es su complejidad computacional. Ambos algoritmos han sido evaluados empíricamente para comparar sus tiempos de ejecución. Para la evaluación, hemos producido una selección de hipergrafos dirigidos generados de forma aleatoria inspirados en modelos muy conocidos de grafos aleatorios como Erdos-Renyi, Newman-Watts-Strogatz and Barabasi-Albert. Varias optimizaciones para ambos algoritmos han sido implementadas y analizadas en la tesis. En concreto, colapsar los componentes fuertemente conexos del grafo dirigido que se puede construir eliminando ciertas hiperaristas complejas del hipergrafo dirigido original, mejora notablemente los tiempos de ejecucion de los algoritmos para varios de los hipergrafos utilizados en la evaluación. Aparte de los ejemplos de aplicación mencionados anteriormente, los hipergrafos dirigidos han sido también empleados en el área de representación de conocimiento. En concreto, este tipo de hipergrafos se han usado para el cálculo de módulos de ontologías. Una ontología puede ser definida como un conjunto de axiomas que especifican formalmente un conjunto de símbolos y sus relaciones, mientras que un modulo puede ser entendido como un subconjunto de axiomas de la ontología que recoge todo el conocimiento que almacena la ontología sobre un conjunto especifico de símbolos y sus relaciones. En la tesis nos hemos centrado solamente en módulos que han sido calculados usando la técnica de localidad sintáctica. Debido a que las ontologías pueden ser muy grandes, el cálculo de módulos puede facilitar las tareas de re-utilización y mantenimiento de dichas ontologías. Sin embargo, analizar todos los posibles módulos de una ontología es, en general, muy costoso porque el numero de módulos crece de forma exponencial con respecto al número de símbolos y de axiomas de la ontología. Afortunadamente, los axiomas de una ontología pueden ser divididos en particiones conocidas como átomos. Cada átomo representa un conjunto máximo de axiomas que siempre aparecen juntos en un modulo. La decomposición atómica de una ontología es definida como un grafo dirigido de tal forma que cada nodo del grafo corresponde con un átomo y cada arista define una dependencia entre una pareja de átomos. En esta tesis introducimos el concepto de“axiom dependency hypergraph” que generaliza el concepto de descomposición atómica de una ontología. Un modulo en una ontología correspondería con un componente conexo en este tipo de hipergrafos y un átomo de una ontología con un componente fuertemente conexo. Hemos adaptado la implementación de nuestros algoritmos para que funcionen también con axiom dependency hypergraphs y poder de esa forma calcular los átomos de una ontología. Para demostrar la viabilidad de esta idea, hemos incorporado nuestros algoritmos en una aplicación que hemos desarrollado para la extracción de módulos y la descomposición atómica de ontologías. A la aplicación la hemos llamado HyS y hemos estudiado sus tiempos de ejecución usando una selección de ontologías muy conocidas del área biomédica, la mayoría disponibles en el portal de Internet NCBO. Los resultados de la evaluación muestran que los tiempos de ejecución de HyS son mucho mejores que las aplicaciones más rápidas conocidas. ABSTRACT Directed hypergraphs are an intuitive modelling formalism that have been used in problems related to propositional logic, relational databases, computational linguistic and machine learning. Directed hypergraphs are also presented as an alternative to directed (bipartite) graphs to facilitate the study of the interactions between components of complex systems that cannot naturally be modelled as binary relations. In this context, they are known as hyper-networks. A directed hypergraph is a generalization of a directed graph suitable for representing many-to-many relationships. While an edge in a directed graph defines a relation between two nodes of the graph, a hyperedge in a directed hypergraph defines a relation between two sets of nodes. Strong-connectivity is an equivalence relation that induces a partition of the set of nodes of a directed hypergraph into strongly-connected components. These components can be collapsed into single nodes. As result, the size of the original hypergraph can significantly be reduced if the strongly-connected components have many nodes. This approach might contribute to better understand how the nodes of a hypergraph are connected, in particular when the hypergraphs are large. In the case of directed graphs, there are efficient algorithms that can be used to compute the strongly-connected components of large graphs. For instance, it has been shown that the macroscopic structure of the World Wide Web can be represented as a “bow-tie” diagram where more than 70% of the nodes are distributed into three large sets and one of these sets is a large strongly-connected component. This particular structure has been also observed in complex networks in other fields such as, e.g., biology. Similar studies cannot be conducted in a directed hypergraph because there does not exist any algorithm for computing the strongly-connected components of the hypergraph. In this thesis, we investigate ways to compute the strongly-connected components of directed hypergraphs. We present two new algorithms and we show their correctness and computational complexity. One of these algorithms is inspired by Tarjan’s algorithm for directed graphs. The second algorithm follows a simple approach to compute the stronglyconnected components. This approach is based on the fact that two nodes of a graph that are strongly-connected can also reach the same nodes. In other words, the connected component of each node is the same. Both algorithms are empirically evaluated to compare their performances. To this end, we have produced a selection of random directed hypergraphs inspired by existent and well-known random graphs models like Erd˝os-Renyi and Newman-Watts-Strogatz. Besides the application examples that we mentioned earlier, directed hypergraphs have also been employed in the field of knowledge representation. In particular, they have been used to compute the modules of an ontology. An ontology is defined as a collection of axioms that provides a formal specification of a set of terms and their relationships; and a module is a subset of an ontology that completely captures the meaning of certain terms as defined in the ontology. In particular, we focus on the modules computed using the notion of syntactic locality. As ontologies can be very large, the computation of modules facilitates the reuse and maintenance of these ontologies. Analysing all modules of an ontology, however, is in general not feasible as the number of modules grows exponentially in the number of terms and axioms of the ontology. Nevertheless, the modules can succinctly be represented using the Atomic Decomposition of an ontology. Using this representation, an ontology can be partitioned into atoms, which are maximal sets of axioms that co-occur in every module. The Atomic Decomposition is then defined as a directed graph such that each node correspond to an atom and each edge represents a dependency relation between two atoms. In this thesis, we introduce the notion of an axiom dependency hypergraph which is a generalization of the atomic decomposition of an ontology. A module in the ontology corresponds to a connected component in the hypergraph, and the atoms of the ontology to the strongly-connected components. We apply our algorithms for directed hypergraphs to axiom dependency hypergraphs and in this manner, we compute the atoms of an ontology. To demonstrate the viability of this approach, we have implemented the algorithms in the application HyS which computes the modules of ontologies and calculate their atomic decomposition. In the thesis, we provide an experimental evaluation of HyS with a selection of large and prominent biomedical ontologies, most of which are available in the NCBO Bioportal. HyS outperforms state-of-the-art implementations in the tasks of extracting modules and computing the atomic decomposition of these ontologies.

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Existe en el panorama edificado un patrimonio construido que se reconoce como Centro Comercial. Un conjunto entendido, en sentido genérico, como familia arquitectónica que tiene características propias y específicas que la identifican. El objeto de la presente tesis doctoral consiste en argumentar que este conjunto constituye un nuevo tipo en el panorama de las tipologías arquitectónicas. Un tipo con entidad propia, que se conecta a una forma diferente de entender la idea de modelo. Un concepto que va más allá de la consideración tradicional del término. Modelo virtual. Este tipo, que surge de una estructura teórica que hemos denominado teoría tipológica, se constituye en una herramienta más para el estudio y el desarrollo proyectual de los espacios arquitectónicos, tanto del propio Centro Comercial como del conjunto de la disciplina arquitectónica, como referencia legítima. El presente trabajo de tesis se inicia con un bloque introductorio denominado Método. Definimos en él una metodología que hemos llamado emocional. Trata de la oportunidad de la tesis. Del porqué de un título que recoge la palabra ignorada. Del interés que suscita el asunto en el contexto del momento presente. Oportunidad e interés en base a una vida profesional dedicada al mundo del Centro Comercial y a la importancia del patrimonio elegido como objeto de estudio. También ha sido un aliciente detectar como las planificaciones del territorio y de los ámbitos de las relaciones colectivas no han sido capaces de integrar un resultado satisfactorio. Quizás por no considerar la complejidad de sus muchas facetas. En consecuencia, el texto busca la esencia del Centro Comercial como soporte para la crítica de su impacto en los nuevos escenarios de relación que la sociedad y el entorno físico imponen. Ámbitos donde los mecanismos históricos del asociacionismo tradicional han dado paso a otros, como el Centro Comercial, de exaltación del individualismo, pero demandados por una sociedad que se identifica con ellos. Espacios que, con Galbraith, existen por de la perversidad intrínseca del binomio consumo-producción que inducen la perplejidad. Ésta pasa a formar parte de la esencia del nuevo espacio comercial, como quedó de manifiesto en el Congreso de Minnesota de 1997, sobre el Centro Comercial. Una sociedad que ha girado hacia el logro material en términos de culto, ocasionando creciente valor significante del consumo. Razón última de la humanidad al decir de Rem Koolhaas. Culto que desemboca en la urgencia de alcanzar niveles de estatus y de identificación con el grupo. Dos parámetros que marcan la relación con el otro. Relación de comparación que excita la necesidad de posesión de objetos que llevaban a recrear en el consumidor la ilusión de ser especiales, de no pasar desapercibidos. El producto de consumo, el objeto, se eleva a la consideración de valor social. En el Centro Comercial se venden valores. Marketing de valores. El deseo del individuo, no la necesidad, queda involucrado en el proceso. La oportunidad y el interés de este estudio surgen además para aclarar el significado de un espacio que sirve al consumidor y a su entorno. Un significado que alcanza sentido, entre otros, por la aparición de un nuevo contexto tras la Segunda Guerra Mundial. Suburbanización, automóvil, nivel de vida, un nuevo papel de la mujer. La Era del Consumo. Una era que genera la paradoja de un individuo con autodeterminación y autosuficiencia crecientes, en un mundo cada vez más condicionado y controlado por dinámicas de ofertas mediatizadas e ilimitadas. La arquitectura en este contexto ha de juzgarse por su relación con un hombre contemporáneo que camina hacia una progresiva excepcionalidad. Cerramos la presentación justificando el término ignorada que aparece en el Título de la Tesis. Subrayamos la escasa existencia de estudios estructurados que relacionen Centro Comercial y arquitectura. Realidad que se constata partiendo del libro de Pevsner, Historia de las Tipologías Arquitectónicas, de 1976. Analizamos también la aceptación que el Centro Comercial, valorado en algunos ámbitos como arquitectura populista. Primer Capítulo, los antecedentes. Se propone un recorrido histórico por la arquitectura comercial de todos los tiempos. El Documento busca concretar las características de la arquitectura comercial a lo largo de la historia para determinar relaciones entre ella y el Centro Comercial. Estas correspondencias van a permitir contestar la pregunta retórica que nos hacemos al inicio del Capítulo: ¿Es la arquitectura del Centro Comercial una arquitectura subsidiaria, o tiene personalidad propia independiente de la del mundo comercial? Con Zevi40, queremos dejar constancia que la relación arquitectura-historia es imprescindible en la tarea proyectual. Un análisis novedoso solo es posible desde la búsqueda de unas raíces auténticas. Así mismo, con Guy de Maupassant, estamos convencidos que “La arquitectura, a través de los siglos, ha tenido el privilegio de dar un símbolo a cada una de las épocas, de resumir con un pequeñísimo número de monumentos típicos, el modo de pensar, de soñar de una raza y de una civilización”. Este recorrido se inicia interpretando la arquitectura comercial minoica. Llegaremos, paso a paso, hasta el siglo XX, los grandes itinerarios comerciales y el Centro Comercial. Se descubren una serie de invariantes que permiten comparar y extraer conclusiones. Resulta novedoso constatar que el Centro Comercial nace para dar respuesta al hombre contemporáneo en su afán consumista. También lo es la rápida implantación y evolución del Centro Comercial en un corto periodo de sesenta años frente al ritmo sosegado de otras soluciones comerciales. Novedad es ver como el comercio y sus arquitecturas nacen abiertos, bajo tenderetes y el Centro Comercial se presenta cerrado. Así mismo, las referencias sacras constituyen un elemento de novedad para la reflexión, en un contexto materialista. Y tantas otras. En Minos, la óptica comercial ofrece otra visión de su legendaria cultura. ¿Palacio o plataforma logística?, gestión centralizada del intercambio, ¿vida pública y vida privada? Así, hasta llegar al siglo XIX. Sus las galerías y sus pasajes acristalados concebidos en primera instancia como medida de recomposición urbana. Espacio entendido desde lo público-privado, desde lo interior-exterior, desde el dentro-afuera, desde lo cerrado-abierto. Con los nuevos mercados de abastos, representan una revolución en el ámbito de la funcionalidad, de la máquina, de la gestión moderna y de las relaciones del ciudadano con la ciudad apoyado en base al intercambio de bienes de consumo. El Centro Comercial es heredero de esta transformación. El Gran Almacén, por otra parte, es el reflejo de otra gran revolución. La que va ligada a la producción y comercialización en masa, las comunicaciones, el precio fijo y el aumento del nivel de vida. El Centro Comercial reinterpreta estas situaciones insertándolas en un nuevo modelo de gestión. En el siglo XX, maestro en técnicas de venta, aparece el hipermercado. El Híper, con su carga de pedagogía, se incorpora al esquema orgánico del Centro Comercial. La tienda en si misma constituye la pieza base de dicho puzle orgánico. Es en esta época cuando la tienda empieza su despegue autónomo como arquitectura, aportando su experiencia. Tras ello, llegamos a las grandes rutas comerciales, que proponemos como metáfora del shopping. Cerramos el capítulo concluyendo con Eugenio Ferrer que “si establecemos una relación entre el espacio y el capitalismo, entonces podemos inferir que los espacios del consumo de masas (ECM) son configuraciones nuevas respecto al pasado (...), pero el sistema que lo introduce no lo es del todo”. Segundo Capítulo. Búsqueda de claves que permitan el reconocimiento del Centro Comercial. Llegados a este punto y con la perspectiva del tiempo cabe preguntarnos, ¿qué entendemos pues por Centro Comercial? ¿Cómo lo percibimos? Abordamos ahora el problema de la percepción del Centro Comercial y su significado. Además de constituirse en símbolo, referencia siempre presente, la eficacia del Shopping es una de las principales causas de su poder de atracción. El Centro Comercial resulta de la síntesis de la revolución del consumo y de la revolución de la gestión. Espacio eficaz del entretenimiento como destino. El usuario resuelve su vida cotidiana dentro de un hábitat que considera propio y que se entiende como el lugar hiperbólico de la transacción comercial. Espacio de la abundancia para el disfrute. Una arquitectura involucrada en esta eficacia. Su sentido del lugar no es otro que el Shopping, que se desenvuelve de forma análoga en todas partes. El hogar del consumidor. Las nuevas catedrales. Las catedrales del consumo. Destino místico. Lugar de peregrinación para el consumidor fervoroso. Espacio sagrado que integra al usuario en la cultura dominante. Cultura del consumo. Templos, donde el tiempo ha perdido su sentido. Paraíso. Un espacio donde la altura, la luz natural, la dimensión general refuerzan el carácter sacro de un espacio para una nueva religión laica. Un espacio seguro, protegido que nos acerca a ideas como la de útero materno, con su carga de calidez y de significación erótica aplicado al encuentro compra-comprador y, ligado a ello, la literatura especializada habla del Centro Comercial como nave espacial hiperesterilizada o de agujero negro que absorbe la energía cultural. Más allá, la simulación, donde se percibe un simulacro de ciudad. Simulacro coherente con todo lo que el Shopping desencadena a su alrededor. El lugar de los sueños, de la fantasía. Aquí los productos se han metamorfoseado en fetiches, en significados. Televisión tridimensional, donde el usuario actúa guiado por una pulsión similar al zapping. Espacio lúdico de la fascinación por comprar o de imaginar que se compra. Espacio de simulaciones que llevan a la ensoñación. Un nuevo lugar que sustituye al espacio cotidiano, con el señuelo de la protección, en un contexto imaginariamente público. Espacio de la hiperrealidad donde no se distingue la realidad de la fantasía, donde tras episodios de confusión y desconcierto, se borran las fronteras con lo imaginario. Espacio mágico, escenario del gran espectáculo del consumo, controlado milimétricamente, al modo de la visita a un gran monumento, que ha de sobrevivir a los tiempos para dar testimonio de nuestro momento. Un icono, un símbolo que transmite un mensaje, que solo el consumidor es capaz de interpretar. Una agitada mezcla, sin precedentes, de percepciones que hablan de perplejidad y asombro ante el fenómeno del Centro Comercial, su espacio y las reacciones del hombre contemporáneo. ¿Cuáles serían las claves que nos permitirían reconocer la calidad esencial de un Centro Comercial, en esta concurrencia de perplejidades? Primero, la función de servicio. Un espacio donde ocurren muchas más cosas que lo obvio, que la compra. Un edificio que se involucra con el entorno de la mano de lo inesperado, la sorpresa y las expectativas. Esta vocación de servicio conecta Centro Comercial y naturaleza arquitectónica. Función que sugiere percepciones ligadas a la experiencia de compra. Organismo que vive y late al unísono con su visitante, colocándose al servicio de sus necesidades, de su afán de consumo, del que vive. Segundo, la comunidad servida. El Centro comercial sirve a una sociedad concreta. La sociedad consumista. Una nueva sociedad que se identifica con el edificio desarrollando un sentido de comunidad al nivel de sus deseos. Esta comunidad que se configura a su alrededor, constituye el activo más poderoso para el éxito de su realidad cotidiana y de su futuro. Tercero, un compromiso de carácter holístico. La economía de la experiencia aplicada al afán consumista de una sociedad identificada con su Centro, da lugar a una experiencia holística planificada. Diseño emocional. Colaboración para el éxito de un conjunto de establecimientos comerciales que participan en la aventura espacio-comercial del Centro Comercial. Ellos son los inductores primarios del consumo. Pero esta colaboración tiene su culminación en la amplificación del mensaje, como un inmenso altavoz, que proviene de la unidad configurada por todos ellos. El reflejo de esta amplificación de mensajes, desde la poderosa unidad constituida, es el aumento de la rentabilidad, fin último de la operación. Cuarto, la forma a través de una identificación de carácter gestáltico. Desde la lectura gestáltica que hacemos de la unidad holística, se advierte una poderosa capacidad de comunicación del sistema con su contexto. Centro y entorno se tornan entonces cómplices que complementan sus realidades. El Centro Comercial, arquitectura estructurada como sistema se percibe –ha de percibirse- como forma unitaria que procede de una mirada de raíz gestáltica que continuamente la recompone desde una óptica espacial y física, ligada a la experiencia individual. Esta unidad formal, más allá de la forma real, se constituye en esencia de de su arquitectura. Quinto, el Centro Comercial como sistema. Un sistema soportado por la Teoría General de Sistemas. La consideración del Centro Comercial como sistema es consecuencia de su estructura holística. El todo no se comporta como la suma de las partes y estas no lo hacen como lo harían en solitario. De aquí surge la necesidad de diálogo permanente entre la comercialización –proceso de incorporación de partes- y su traducción al mundo del diseño –proceso de articular arquitectónicamente las partes. Como sistema así configurado, el Centro Comercial se inserta en el paradigma contemporáneo, lo que genera realidades duales que no son excluyentes y reacciones de perplejidad e incertidumbre que el sistema corrige con su capacidad de autorregulación. Aparece también el espectador cuántico, el visitante, el consumidor, que interactúa con el sistema. Desde las herramientas que nos aporta la idea de sistema complejo, afrontamos el Mix Comercial -en definitiva la eficaz localización de las piezas en orden a sus relaciones y al organismo resultante- y su incidencia en la arquitectura que estamos concibiendo. Una arquitectura impredecible por lo mutable, que se erige en reto de la operación y del diseñador. Diseño que, de la mano del concepto de sistema se convierte en herramienta a mayor gloria de la operación global. El debate del estilismo no será más que el resultado del análisis en busca del éxito de esta operación. Sexto, una arquitectura de la negociación. Negociación como mecanismo proyectual y como resultado. La solución de proyecto nunca resulta evidente en el Centro Comercial como consecuencia de lo imprevisible del propio proceso de configuración. Su concreción solo puede ser fruto del compromiso de todos los agentes por conseguir el objetivo de la operación. Esto se consigue desde el equilibrio de intereses. Comerciales y de diseño. Un compromiso con la negociación y una negociación íntimamente ligada a la coordinación. Séptimo, el espacio y el tiempo. El debate espacio-tiempo condiciona y estructura la percepción del Centro Comercial. Introducimos conceptos como cronotopo –el instante y el lugar donde ocurre algo- y paradoja –incoherencia de la relación causa efecto- que sitúan el vínculo entre el tiempo y el espacio del Centro Comercial en un contexto de Shopping. En el discurrir paralelo del tiempo histórico –el tiempo de fuera- y del tiempo interior, el de dentro del Centro Comercial –tiempo presente o intemporalidad-, se produce el triunfo social del Centro Comercial que se traduce en haber sabido resolver en el espacio y en el tiempo las paradojas postmodernas del hombre contemporáneo. Octavo, de lo global. Globalidad que no es ajena a lo local. Una arquitectura que insertada en la dinámica de una economía de ámbito mundial, refleja las contradicciones que ella impone, fundamentalmente en los procesos de inclusión y exclusión, afectando de manera decisiva al debate de lo local, que el Centro Comercial debe incorporar como herramienta ineludible de reconocimiento. Terminamos el capítulo segundo manifestando como estas ocho claves, asumidas en su conjunto, confirman que el Centro Comercial puede aparecer como un todo conceptual cohesionado, pasando a formar parte de una familia arquitectónica coherente, cuya estructura funcional somos capaces de establecer. El Capítulo Tercero presenta con detalle la figura del arquitecto Víctor Gruen, creador reconocido del moderno Centro Comercial. Presentamos su trayectoria profesional observando como las diferentes claves analizadas en capítulos anteriores van apareciendo de manera natural a lo largo de ella "Victor Gruen may well have been the most influential architect of the twentieth century." Malcolm Gladwell. The Terrazo Jungle. Fifty Years Ago, The Mall Was Born. America Never Would Be The Same. 2004. In The New Yorker. Hombre complejo, conflictivo. Las paradojas a lo largo de su carrera fueron notables. Sin embargo siempre apareció como un hombre recto. Garret Eckbo, reconocido paisajista y colaborador de Gruen en el Centro Comercial peatonal del Centro urbano de Fresno, California, se asombraba de que alguien como Gruen hubiese sido capaz de combinar cortesía y humanidad en la carrera de ratas (sic) en la que se convirtió el universo de la comercialización americana y mantener la integridad542. Philip Johnson, en 1962, ponderando las muchas habilidades de Gruen manifestó que no estaba seguro si alguno de ellos, arquitectos artistas, hubiera sido capaz de hacer lo que Gruen hizo. A más, sobre Gruen, manifestó lo siguiente: "... El va más allá de la creación de un bello edificio. En jugar con la gente y sugerir lo que tienen que hacer, es un maestro. Y obtiene buenos resultados como hace la escultura. El suyo es un arte cívico, un sentido cívico.... Él es capaz de sentarse y poner cosas juntas. No es pomposo ni vano. Yo no me reuniría con él para hablar del diseño (de edificios). Víctor siente que cuando se habla de diseño se está ignorando todo el contexto... Su arquitectura es poderosamente limpia, no vuela la fantasía. Pero cuando te haces con su complejidad, ves que has descubierto algo más allá del diseño.... No puedes decir que haya alguien como él. La arquitectura tiene la suerte de tenerle como arquitecto..." Philip Johnson. Article in Fortune Review. 1962. El Documento de tesis cierra la visión de Gruen realizando un recorrido por los diferentes capítulos de su libro esencial, Shopping Towns Usa: The Planning of Shopping Centers. Solo su índice resulta un monumento al proceso de gestación del Centro Comercial. El libro, aquí simplemente mostrado en su estructura básica como un silencioso testigo, es la referencia canónica los Centros Comerciales contemporáneos, desde su aparición. . El Cuarto Capítulo del Documento de tesis es una recapitulación del trabajo anterior, en el que se sintetizan los conceptos de función y estilo relacionados con el Centro Comercial, se define en qué consiste cada uno de ellos y como, a partir de ahí, podemos afirmar que nos encontramos ante un tipo arquitectónico nuevo en el panorama de la disciplina arquitectónica. Terminamos el Capítulo integrando el Centro Comercial con un cuerpo teórico de referencias que se remiten a un tipo arquitectónico concreto y particular, acogiendo su singularidad como fenómeno arquitectónico autónomo. Como Conclusión de la tesis, resultado de todo lo anterior es decir, como consecuencia de la integración de un torrente de percepciones e intuiciones en un cuerpo teórico de referencias, deducidas de la existencia de unas claves que estructuran y penetran la esencia del singular modelo estudiado, haciéndolo detectable y seductor, resultan las características de un tipo arquitectónico con entidad propia que ordena, orienta y supedita la realidad y la existencia de esta nueva arquitectura. Una arquitectura nunca antes definida como tal, en el panorama tipológico de la disciplina. Teoría tipológica para una nueva arquitectura, que hemos ido proponiendo a lo largo del trabajo y que es coherente con los diferentes parámetros que se han analizado. Un conjunto edificado que, desde el estudio de sus claves esenciales y de sus invariantes perceptibles, aparece ahora más cercano, más familiar. Tanto que es posible destilar desde este conocimiento cercano e íntimo, una síntesis útil como referencia proyectual y como referencia para las grandes cuestiones que preocupan al discurrir del debate arquitectónico y sus ideas. El debate de la disciplina. El objeto de esta tesis, que consistía en establecer que el conjunto edificado que conocemos como Centro Comercial se constituye en un nuevo tipo en el panorama de las tipologías arquitectónicas, entendido el Centro Comercial en sentido genérico como familia arquitectónica con características propias y específicas que la hacen autónoma y reconocible, queda a nuestro juicio argumentado y justificado. ABSTRACT Within the frame of the built heritage there is a construction that is recognized as Shopping Center. An ensemble understood as an architectural family with its own specific recognizable characteristics. This thesis aims to explain that this building complex constitutes a new type in the panorama of architectural typology. This typology, with its singular identity, is connected to a way of understanding the idea of the model beyond an orthodox conception of the term understood as virtual model. This typology comes from a theoretical structure that we called typological theory, and it serves as yet another tool to reference the study and development design of the architectural spaces. In this first section, the Method, we emotionally explore the opportunities of this thesis. Why this typology has been ignored and the interest this work has in the present moment. An opportunity and an interest explained from an experience of a life dedicated to the world of Shopping Centers. The text then introduces the need for a rigorous knowledge of the Shopping Center’s essence in order to understand its impact in the frame of a new society and a new physical environment. A frame time where the historical mechanisms of association of civic community have given way to other gathering spaces like the Shopping Center, which encourages individualism, but is demanded by a society that relates to them. Spaces that, according to Galbraith, are a result of the intrinsic perversity of the unstoppable movement of the wheel of consumption-production. A society that has turned to worship of material achievement. Worship that provokes the appearance of an increasing value of consumption, according to Koolhaas, the only goal of humanity. Worship that ends in the need to reach certain status levels in the plane of a permanent comparison where the need of possession excites the consumer and gives them the illusion of being special. The product of consumption rises up to consideration of social values, entering a dynamic of marketing values, not only objects, but the desire of the individual remains. The study appears also to clarify the meaning of a space that serves the consumer and its context. A meaning that makes sense with the appearance of the suburbanization, the massive utilization of the car, the increase of living standards and the new role of women in the society after the Second World War, giving rise to the Age of Consumption. A world now determined and controlled by media and unlimited offers, where it’s necessary to place them in the context of the ordinary. An architecture that has to be judged precisely for its relation with this specific contemporary man. This section ends justifying the term ignored that appears in the Title of the Thesis, considering it in relation with the lack of studies structured about the Shopping Center and its architecture, drawing from Pevsner's work, A history of building types, 1976. Finally, the Shopping Center is analyzed with the most critical of thoughts, which considers it as populist architecture. The First Chapter, Precedents, proposes an historical tour of the commercial architecture throughout history. The Document looks to place on record the characteristics of the commercial architecture to set the connection between them and the Mall itself. These correspondences are going to allow us to answer the rhetorical question: is it the architecture of the Shopping Center a subsidiary architecture, or does it have its own personality independent from that of the commercial world? The reason of this historical search, citing Bruno Zevi, is that it is indispensable to establish the relationship between architecture and history, understating that an analysis is only possible when researching for their roots. Moreover, according to Guy de Maupassant, we are sure that architecture has had the privilege, across the centuries, of symbolizing as it were each age(…), through the harmony of lines and the charm of ornamentation all the grace and grandeur of an epoch. This historical reading, inseparable from a consistent design action, begins interpreting the commercial architecture of the Minoan to the 20th Century. Though this analysis of the big commercial itineraries and the study of the Shopping Center itself. A reading where we have found a series of constants that make it possible to draw conclusions from this comparison. The Mall appears to give response to the needs of a consumerist society. Comparing to the calm pace of the evolution of other commercial solutions, it is relevant its fast implantation and evolution in a short period of sixty years. Though via different solutions, the commercial spaces are considered taking into account the public-private relation, the interior-exterior, the inside-out, the closed-opened. Through that, the 19th century galleries and the food markets represent a revolution in functionality, in the machine, the modern management and the relations of the citizen within the city. All of this, the Mall inheritor feels. Likewise, the Department Store is the reflection of another great revolution. Production and commercialization en-mass, communications, the fixed price and increase of the living standard. The Mall reinterprets these situations inserting them in a new model of management. Already in the 20th century Mall and mass technologies of sale, the hypermarket is enthusiastically incorporated into the configuration of this organic scheme, constituting the base of one of the models, the French, that will be highly developed in the European continent. The shop itself constitutes, on the other hand, the key piece that completes the puzzle of the Mall and is in this epoch when it starts taking off as architecture, has an autonomous character. After all this, finally, we come to the big commercial routes, which we propose as metaphor of the shopping. Citing Eugenio Ferrer we can conclude that “If we establish a relation between the space and the capitalism, then we can infer that the spaces of the consumption of masses (ECM) are new configurations with regard to the past (...), but the system that introduces it it is not completely” Now we arrive at this point and with the perspective of time it is necessary to ask us, what do we understand about the Shopping Center? How do we perceive it? The second Chapter approaches the problem of the perception of the Mall and from this it is possible to detect and to identify key drivers that orientate the architectural comprehension of the space. The efficiency of the Shopping Center is its main power of attraction. A world that has ensued from the synthesis of the revolution of consumption and management. An effective cavern-like place of entertainment where the user, the consumer, the postmodern man solves his daily life inside a considered habitat. The hyperbolic place of commercial transaction. An abundance of space, that makes us perceive it as destination of entertainment. An architecture has evolved this efficiency, where the sense of place is at one with the sense of the Shopping. The home of the consumer. The new cathedrals. The cathedral of consumption. The place of peregrination for the fervent consumer. A sacred space that integrates the user in the dominant culture. A temple, where time itself has stopped existing. In this paroxysm, an expression of the Garden of Eden or Paradise itself. A space where the height, the natural daylight and the spatial dimension reinforce the sacred character of a new lay religion. Another common perception is that of a protected area, which leads to metaphors and considerations that suggest the idea of maternal womb, with its weight of erotic meaning, referring to the encounter of the shopper making a purchase. The literature also tells us about its perception as a sterile space capsule, a black hole that absorbs all cultural energy. Likewise, a world simulation where a mock city is perceived at first instance. Consistent with all that shopping triggers inside. A city, a space conceived as a place of dreams, fantasy, where the products have been metamorphosed into fetishes. Entertaining a television, three-dimensional television, where the user acts guided by a drive similar to zapping. A play area where the latest fascination is in the act of buying. Space simulations that unite and transcend creating atmospheres that lead to reverie. A new space replacing the daily space with the lure of safe space in a public context. A hyper-reality space with reality and fantasy, where borders are erased with imaginary episodes of confusion and bewilderment, without distinction. The charm and fascination of a space that reads like magic. The magic of a space which is defined as stage extravaganza, the large theatre, the consumer surveys in the fine control mode in which you visit a national monument. The shopping center has to survive the times to be a testimony of our time. An icon, a symbol that conveys a message, the message reads ‘consumer’. In short, a Shopping Center is a mix of unprecedented insights that speak of a widespread phenomenon of bewilderment. Its space and the reactions of contemporary man unfold in it like a fish in water. What are the key aspects which allow us to recognize the essential quality of a shopping center in this concurrence of perplexities? First, we want to record a service function of space much deeper than the immediately obvious, i.e. a purchase occurs. A building that appears to be involved with the environment and its people from the hand of the unexpected circumstances; surprise and attention. And that, in turn, also involves the visitor beyond the purchase. This dedication to service closely links the mall with its architectural nature. It is not the function of a lifeless machine. It is a feature that suggests unsuspected perceptions linked to the purchase, which speaks of an organism that lives and breathes in unison with the visitor. Second, in addition to the vocation of service-oriented desire for consumption, the Mall environment serves a particular society - The consumer society. A new society which relates to building a sense of community developed to the level of their desires. This community also constitutes the most powerful asset to the success of the daily life of the Shopping Center. Third, we emphasize that the so called economy of the experience is combined with the consumer zeal of a company that is identified by the Shopping Center. It connects to form a holistic and planned experience. This experience takes shape in the entity that ensues from the premeditated association and synergy, in the sense of a collaboration for success. A set of concrete commercial and independent establishments, take part in the spatial and commercial adventure that is the Mall and they are the instigators of the consumption. This holistic behavior finds culmination in the amplification of a claim that becomes unitary, like an immense force that leads to an increased profitability to all the levels. Consummation is a reference of one human being overturned in an architecture assimilated into a legitimate, emotional design with stability. A holistic quality is born of the essence of the building - and by virtue of the Conditions of Alexander, Christopher Alexander, determines the system condition of the Shopping Center. Fourth, we propose to establish what character the Mall will form when joined with the concept of its typology. This is going to allow the architectural work to be formed. As a result of the holistic structure that we see, the Mall is perceived as a system whose parts have their own function, justifying their existence in the ecosystem. Across a gestalt there is a powerful capacity of communication between the system and its context. We visualize on the one that stands out our building, turning both, Center and environment, in accomplices of a few special relations who complement each other in his realities. This relationship within a complex and diverse environment gives the Mall a range of unique spatial perceptions, the result of disparate experiences, which because of its root origin of gestalt, are integrated into a unified and coordinated manner fully intelligible and organized. This is the final formal essence of the Shopping Center. We can conclude here that the Mall as architecture is a structured system and should be perceived as a unit both from a physical and spatial perspective as this is the essence of its architecture. Fifth, the Mall as a system. A system which is being supported by a broad theoretical corpus, the General Systems Theory, which offers sufficient methodology to descend into consideration and give an enlightened conclusion on the overall understanding of the Mall. Consideration of the Mall as a system is a result of its holistic structure. The whole does not behave like any of the parties and they do not behave the way they used to before belonging to the whole, because they inhibit many of their qualities to their advantage. It arises the need for an ongoing dialogue between marketing processes and its translation into the physical world, the design. The system generates multiple perceptions to be integrated into a body which is to be understood as unitary. As a system, the Mall is inserted into the contemporary paradigm, creating dual realities that are not exclusive and are reactions of uncertainty that the system be properly designed at all levels, faced with their ability to self-regulate. Likewise, considering the visitor, the customer, like the quantum spectator who interacts with the system permanently. Moreover, a complex system confronts us with the Commercial mix, the effective location of parts in order to relate to the body and its importance in the architecture we are conceiving. Unpredictable architecture, which stands as the challenge of the operation and the designer. Design that becomes the tool of the system to create success for the overall operation. The discussion of the styling is merely the result of analysis that also seeks the success of the system, i.e. the styling should send the right message for the environment to ensure its survival. Sixth, the idea of negotiation as an architecture project, a mechanism inherent to the status of the proposed system. The project solution is never evident at the Shopping Center because of the unpredictability of the process itself. It can only be the fruit of the commitment of all stakeholders to achieve the objective of the operation. This is achieved from the balance of interests, of commercial and design. A commitment to negotiation and a negotiation linked to coordination. The pursuit of stability is key, as instability is always present and constantly requires strategies to build the object you are configuring. Seventh, proposes space-time itself as a circumstance that determines and structures the perception of the Mall in a singular way. We introduce concepts as chronotope and paradox to help us place the relationship between time and space within the Mall in the context of shopping. A consequence of the parallel flow of historical time - the time outside - and the time inside the Mall, the big shopping center formula is precisely that of having the feeling of timelessness in the space. The social triumph of the mall is the ability to resolve in space and in time all postmodern paradoxes and, beyond that, of contemporary man, condensing into a small space and time an enormous amount of cultural symbols, often contradictory, but they attract the practice of consumerism. Eighth, global level. Globalization which doesn’t ignore the local level. Architecture that is inserted into the dynamics of a global economy, reflects the contradictions that it imposes, mainly in the processes of inclusion and exclusion. Inclusion and exclusion affect the debate of the local level, which the Mall must incorporate as an unavoidable tool of recognition. The eight fundamental principles, when applied as a whole, confirm that the built heritage, which corresponds to the general Mall idea, can be presented as a cohesive conceptual whole. This becomes part of a coherent architectural family, whose functional structures are able to be established. The Third chapter presents in a detailed way the figure of the architect Victor Gruen, recognized as the creator of the modern Mall. Studying his professional experience, it is shown how the different keys analyzed in previous chapters are appearing in a natural way. "Victor Gruen may well have been the most influential architect of the twentieth century." Malcolm Gladwell. The Terrazo Jungle. Fifty Years Ago, The Mall Was Born. America Never Would Be The Same. 2004. In The New Yorker. He was a complex, troubled man and the paradoxes along his career were notable. Nevertheless, always he appeared as a straight man. Garret Eckbo, the recognized landscape painter and collaborator of Gruen was astonished how Gruen had been capable of combining comity and humanity in this career of rates, into that the American commercialization turned, Johnson, in 1962, weighting many Gruen's skills demonstrated that he was not sure if anyone of them, architects artists, had been capable of doing what Gruen did. He goes beyond just the creation of a beautiful building. In playing on people and suggesting what they ought to do, he is a master. (…) his architecture is clean - hardly architecture, no flights of fancy. But when you get hold of its complexity, you've got something beyond the design... You can't say there's someone like him. Architecture is lucky to have him as an architect." Philip Johnson. Article in Fortune Review. 1962. The Document of the thesis closes with Gruen's vision of realizing a tour through the different chapters of his essential book, Shopping towns USA: The Planning of Shopping Centers. It’s mere index turns out to be a monument to the process of the gestation of the Mall. The book, simply acted in its basic structure as a silent witness, as the canonical reference for the contemporary Malls. The Fourth Chapter of the Document of the thesis is a recapitulation of the previous work, which synthesizes the concepts of function and style related to the Shopping Center, and clearly defines how they are defined so we can conclude that we have found an architectural new type in the panorama of the architectural discipline. Therefore, the Conclusion of the thesis integrates this development in a theoretical body of references that relate to an architectural specific and particular type, which receives the singularity of the Shopping Center as an architectural independent phenomenon as it has tried to demonstrate from the beginning of the work. To conclude, as a result of the integrative process and the development of the theoretical body of references, the essential characteristics of the order and concept of the architectural typology form the existence of a new architecture; architecture never before defined as such, in the theoretical typology of the discipline. A theoretical typology for a new architecture is proposed throughout the discussed research and forms a conclusion of the different parameters that have been analysed. As a building complex, from the study of the essential characteristics and of the perceptible constants, the typology is more clearly defined and thus, becomes a useful tool and precedent for the consideration of the discipline. The thesis then justifies how the building complex known as Shopping Center constitutes a new type of architectural typology.

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We have recently shown that VEGF functions as a survival factor for newly formed vessels during developmental neovascularization, but is not required for maintenance of mature vessels. Reasoning that expanding tumors contain a significant fraction of newly formed and remodeling vessels, we examined whether abrupt withdrawal of VEGF will result in regression of preformed tumor vessels. Using a tetracycline-regulated VEGF expression system in xenografted C6 glioma cells, we showed that shutting off VEGF production leads to detachment of endothelial cells from the walls of preformed vessels and their subsequent death by apoptosis. Vascular collapse then leads to hemorrhages and extensive tumor necrosis. These results suggest that enforced withdrawal of vascular survival factors can be applied to target preformed tumor vasculature in established tumors. The system was also used to examine phenotypes resulting from over-expression of VEGF. When expression of the transfected VEGF cDNA was continuously “on,” tumors became hyper-vascularized with abnormally large vessels, presumably arising from excessive fusions. Tumors were significantly less necrotic, suggesting that necrosis in these tumors is the result of insufficient angiogenesis.

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In cycling cells, the retinoblastoma protein (pRb) is un- and/or hypo-phosphorylated in early G1 and becomes hyper-phosphorylated in late G1. The role of hypo-phosphorylation and identity of the relevant kinase(s) remains unknown. We show here that hypo-phosphorylated pRb associates with E2F in vivo and is therefore active. Increasing the intracellular concentration of the Cdk4/6 specific inhibitor p15INK4b by transforming growth factor β treatment of keratinocytes results in G1 arrest and loss of hypo-phosphorylated pRb with an increase in unphosphorylated pRb. Conversely, p15INK4b-independent transforming growth factor β-mediated G1 arrest of hepatocellular carcinoma cells results in loss of Cdk2 kinase activity with continued Cdk6 kinase activity and pRb remains only hypo-phosphorylated. Introduction of the Cdk4/6 inhibitor p16INK4a protein into cells by fusion to a protein transduction domain also prevents pRb hypo-phosphorylation with an increase in unphosphorylated pRb. We conclude that cyclin D:Cdk4/6 complexes hypo-phosphorylate pRb in early G1 allowing continued E2F binding.

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Homologous recombination contributes both to the generation of allelic diversity and to the preservation of genetic information. In plants, a lack of suitable experimental material has prevented studies of the regulatory and enzymatic aspects of recombination in somatic and meiotic cells. We have isolated nine Arabidopsis thaliana mutants hypersensitive to x-ray irradiation (xrs) and examined their recombination properties. For the three xrs loci described here, single recessive mutations were found to confer simultaneous hypersensitivities to the DNA-damaging chemicals mitomycin C (MMCs) and/or methyl methanesulfonate (MMSs) and alterations in homologous recombination. Mutant xrs9 (Xrays, MMSs) is reduced in both somatic and meiotic recombination and resembles yeast mutants of the rad52 epistatic group. xrs11 (Xrays, MMCs) is deficient in the x-ray-mediated stimulation of homologous recombination in somatic cells in a manner suggesting a specific signaling defect. xrs4 (Xrays, MMSs, MMCs) has a significant deficiency in somatic recombination, but this is accompanied by meiotic hyper-recombination. A corresponding phenotype has not been reported in other systems and thus this indicates a novel, plant-specific regulatory circuit linking mitotic and meiotic recombination.

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B cell development and humoral immune responses are controlled by signaling thresholds established through the B lymphocyte antigen receptor (BCR) complex. BCR signaling thresholds are differentially regulated by the CD22 and CD19 cell surface receptors in vivo. B cells from CD22-deficient mice exhibit characteristics of chronic stimulation and are hyper-responsive to BCR crosslinking with augmented intracellular Ca2+ responses. By contrast, B cells from CD19-deficient mice are hypo-responsive to transmembrane signals. To identify signaling molecules involved in the positive and negative regulation of signaling thresholds, the signal transduction pathways activated after BCR crosslinking were examined in CD22- and CD19-deficient B cells. These comparisons revealed that tyrosine phosphorylation of Vav protein was uniquely augmented after BCR or CD19 crosslinking in CD22-deficient B cells, yet was modest and transient after BCR crosslinking in CD19-deficient B cells. Ligation of CD19 and CD22 in vivo is likely to positively and negatively regulate BCR signaling, respectively, because CD19 crosslinking was more efficient than BCR crosslinking at inducing Vav phosphorylation. However, simultaneous crosslinking of CD19 with the BCR resulted in a substantial decrease in Vav phosphorylation when CD22 was expressed. Thus, the differential regulation of Vav tyrosine phosphorylation by CD19 and CD22 may provide a molecular mechanism for adjusting BCR signaling thresholds.

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Mitogen-activated protein (MAP) kinases are pivotal components of eukaryotic signaling cascades. Phosphorylation of tyrosine and threonine residues activates MAP kinases, but either dual-specificity or monospecificity phosphatases can inactivate them. The Candida albicans CPP1 gene, a structural member of the VH1 family of dual- specificity phosphatases, was previously cloned by its ability to block the pheromone response MAP kinase cascade in Saccharomyces cerevisiae. Cpp1p inactivated mammalian MAP kinases in vitro and acted as a tyrosine-specific enzyme. In C. albicans a MAP kinase cascade can trigger the transition from the budding yeast form to a more invasive filamentous form. Disruption of the CPP1 gene in C. albicans derepressed the yeast to hyphal transition at ambient temperatures, on solid surfaces. A hyphal growth rate defect under physiological conditions in vitro was also observed and could explain a reduction in virulence associated with reduced fungal burden in the kidneys seen in a systemic mouse model. A hyper-hyphal pathway may thus have some detrimental effects on C. albicans cells. Disruption of the MAP kinase homologue CEK1 suppressed the morphological effects of the CPP1 disruption in C. albicans. The results presented here demonstrate the biological importance of a tyrosine phosphatase in cell-fate decisions and virulence in C. albicans.

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Hypertension is a common trait of multifactorial determination imparting an increased risk of myocardial infarction, stroke, and end-stage renal disease. The primary determinants of hypertension, as well as the factors which determine specific morbid sequelae, remain unknown in the vast majority of subjects. Knowledge that a large fraction of the interindividual variation in this trait is genetically determined motivates the application of genetic approaches to the identification of these primary determinants. Success in this effort will afford insights into pathophysiology, permit preclinical identification of subjects with specific inherited susceptibility, and provide opportunities to tailor therapy to specific underlying abnormalities. To date, mutations in three genes have been implicated in the pathogenesis of human hypertension: mutations resulting in ectopic expression of aldosterone synthase enzymatic activity cause a mendelian form of hypertension known as glucocorticoid-remediable aldosteronism; mutations in the beta subunit of the amiloride-sensitive epithelial sodium channel cause constitutive activation of this channel and the mendelian form of hypertension known as Liddle syndrome; finally, common variants at the angiotensinogen locus have been implicated in the pathogenesis of essential hypertension in Caucasian subjects, although the nature of the functional variants and their mechanism of action remain uncertain. These early findings demonstrate the feasibility and utility of the application of genetic analysis to dissection of this trait.

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The repair of DNA double-strand breaks in Saccharomyces cerevisiae requires genes of the RAD52 epistasis group, of which RAD55 and RAD57 are members. Here, we show that the x-ray sensitivity of rad55 and rad57 mutant strains is suppressible by overexpression of RAD51 or RAD52. Virtually complete suppression is provided by the simultaneous overexpression of RAD51 and RAD52. This suppression occurs at 23 degrees C, where these mutants are more sensitive to x-rays, as well as at 30 degrees C and 36 degrees C. In addition, a recombination defect of rad55 and rad57 mutants is similarly suppressed. Direct in vivo interactions between the Rad51 and Rad55 proteins, and between Rad55 and Rad57, have also been identified by using the two-hybrid system. These results indicate that these four proteins constitute part of a complex, a "recombinosome," to effect the recombinational repair of double-strand breaks.

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A matéria orgânica do solo (MOS) representa um importante reservatório de carbono (C) nos ecossistemas terrestres. O conteúdo de C estocado no solo pode ser liberado para a atmosfera na forma de CO2, com a decomposição da MOS, ou pode ser aumentado com a entrada de resíduos e retenção da MOS. Nesse sentido, é importante entender os mecanismos de estabilidade e retenção da MOS para predizer como os solos respondem a mudanças, quer sejam elas induzidas por alterações climáticas ou por práticas de manejo. Dentro dos Latossolos, classe que ocupa cerca de 32 % do território brasileiro, há aqueles que possuem horizonte A húmico hiper espesso e, portanto, com maior estoque de C. Aspectos sobre a origem, formação e preservação do horizonte A húmico destes solos em suas ocorrências em diferentes biomas ainda não foram completamente elucidados e estão estritamente ligados à fonte, dinâmica e mecanismos de preservação e distribuição da MOS no solo. O objetivo deste trabalho é entender a gênese da MO dos Latossolos húmicos que ocorrem no Bioma Cerrado, por meio da caracterização molecular pela técnica da pirólise acoplada à cromatografia gasosa e espectroscopia de massas (pirólise - CG/EM). Para isso, foram coletadas amostras dos horizontes A em dois perfis de Latossolos com horizonte A húmico (LH1, LH2) e um perfil de Latossolo com horizonte A moderado (solo de referência; LNH) situados em superfície de aplanamento adjacente à Serra do Espinhaço, no município de Grão Mogol - MG, sob clima tropical semi-úmido e vegetação de cerrado sensu strictu. Por meio da descrição morfológica dos solos em diferentes níveis de observação (campo, lupa e microscópio) procurou-se entender melhor os mecanismos de espessamento do horizonte A e a distribuição de partículas de carvão ao longo do perfil. As amostras dos horizontes foram submetidas ao fracionamento físico e extração da MOS, gerando as seguintes frações: fração leve livre (FLL); fração leve oclusa (FLO), fração extraível com NaOH (EXT) e resíduo (RES). A morfologia dos perfis evidencia a intensa e longa atividade biológica (fauna e raízes) a que esses solos foram e estão submetidos. Isso explica a abundância de microagregados e a consequente macropososidade elevada, assim como a ampla distribuição de fragmentos de carvão em todo o horizonte A, e parte do B, com dimensões milimétricas a submilimétricas, sugerindo a fragmentação destes ao longo do tempo. Foi evidenciado o maior conteúdo de carvões nos dois LHs em comparação ao LNH. A distribuição da MOS nas frações estudadas foi a mesma para os três perfis estudados: RES>EXT>FLL>FLO, que mostra a importância da fração RES para estes solos. Produtos da carbonização (Black carbon; BC: hidrocarbonetos poliaromáticos) foram mais abundantes na fração RES e FLO, no entanto, a maior diferença qualitativa entre a MOS de LHs e LNH diz respeito à abundância de BC na fração RES, que é maior em LHs do que LNH; confirmando a maior quantidade de carvões em LHs verificada na morfologia. Um índice de degradação do BC foi estabelecido com base em análise fatorial com os todas as frações estudadas e produtos poliaromáticos. Este índice, aplicado às frações EXT e RES, mostrou que a degradação do BC aumenta com a profundidade/idade, e não houve diferenças significativas entre os perfis estudados. Portanto, LHs provavelmente tem maior entrada de carvões, o que deve estar ligado a um histórico de maior incidência de incêndios ou maior abundância local de espécies arbóreas.

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The rise and growth of large Jewish law firms in New York City during the second half of the twentieth century was nothing short of an astounding success story. As late as 1950, there was not a single large Jewish law firm in town. By the mid-1960s, six of the largest twenty law firms were Jewish, and by 1980, four of the largest ten prestigious law firms were Jewish firms. Moreover, the accomplishment of the Jewish firms is especially striking because, while the traditional large White Anglo-Saxon Protestant law firms grew at a fast rate during this period, the Jewish firms grew twice as fast, and they did so in spite of experiencing explicit discrimination. What happened? This book chapter is a revised, updated study of the rise and growth of large New York City Jewish law firms. It is based on the public record, with respect to both the law firms themselves and trends in the legal profession generally, and on over twenty in-depth interviews with lawyers who either founded and practiced at these successful Jewish firms, attempted and failed to establish such firms, or were in a position to join these firms but decided instead to join WASP firms. According to the informants interviewed in this chapter, while Jewish law firms benefited from general decline in anti-Semitism and increased demand for corporate legal services, a unique combination of factors explains the incredible rise of the Jewish firms. First, white-shoe ethos caused large WASP firms to stay out of undignified practice areas and effectively created pockets of Jewish practice areas, where the Jewish firms encountered little competition for their services. Second, hiring and promotion discriminatory practices by the large WASP firms helped create a large pool of talented Jewish lawyers from which the Jewish firms could easily recruit. Finally, the Jewish firms benefited from a flip side of bias phenomenon, that is, they benefited from the positive consequences of stereotyping. Paradoxically, the very success of the Jewish firms is reflected in their demise by the early twenty-first century: because systematic large law firm ethno-religious discrimination against Jewish lawyers has become a thing of the past, the very reason for the existence of Jewish law firms has been nullified. As other minority groups, however, continue to struggle for equality within the senior ranks of Big Law, can the experience of the Jewish firms serve as a “separate-but-equal” blueprint for overcoming contemporary forms of discrimination for women, racial, and other minority attorneys? Perhaps not. As this chapter establishes, the success of large Jewish law firms was the result of unique conditions and circumstances between 1945 and 1980, which are unlikely to be replicated. For example, large law firms have become hyper-competitive and are not likely to allow any newcomers the benefit of protected pockets of practice. While smaller “separate-but-equal” specialized firms, for instance, ones exclusively hiring lawyer-mothers occasionally appear, the rise of large “separate-but-equal” firms is improbable.

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Numerical modelling methodologies are important by their application to engineering and scientific problems, because there are processes where analytical mathematical expressions cannot be obtained to model them. When the only available information is a set of experimental values for the variables that determine the state of the system, the modelling problem is equivalent to determining the hyper-surface that best fits the data. This paper presents a methodology based on the Galerkin formulation of the finite elements method to obtain representations of relationships that are defined a priori, between a set of variables: y = z(x1, x2,...., xd). These representations are generated from the values of the variables in the experimental data. The approximation, piecewise, is an element of a Sobolev space and has derivatives defined in a general sense into this space. The using of this approach results in the need of inverting a linear system with a structure that allows a fast solver algorithm. The algorithm can be used in a variety of fields, being a multidisciplinary tool. The validity of the methodology is studied considering two real applications: a problem in hydrodynamics and a problem of engineering related to fluids, heat and transport in an energy generation plant. Also a test of the predictive capacity of the methodology is performed using a cross-validation method.

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Este artículo estudia la redefinición del lenguaje periodístico ante la influencia de tres tendencias de la comunicación digital: el Search Engine Optimization (SEO), la inmediatez de las redes sociales y la fragmentación de contenidos mediante enlaces. Para ello, se compara el punto de vista de los editores web de los ocho medios españoles con mayor audiencia con las iniciativas implantadas en sus redacciones y las aportaciones teóricas sobre la escritura ciberperiodística. Este análisis revela la importancia que los medios digitales otorgan a la creación de contenidos adaptados a la web, pero también sus carencias en la adopción de acciones concretas para favorecer su desarrollo.

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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

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La sclérodermie (SSc) est une maladie rare affectant les personnes génétiquement prédisposées d’une réponse immunitaire défectueuse. Malgré les derniers avancements et développements dans le domaine, l’étiologie et la pathogénèse de la maladie demeurent peu comprises. Par ailleurs, il y a un ralentissement dans la compréhension de cette maladie à cause du manque de modèle animal représentatif de la SSc humaine. Malgré plusieurs lacunes, les souris traitées avec la bléomycine ou portant des modifications génétiques (TSK-1) sont très utilisées dans les études précliniques de la SSc mais elles ne présentent pas toutes les caractéristiques de cette maladie. Pour contribuer à la recherche sur la SSc, la stagiaire postdoctorale Dre Heena Mehta a développé dans le laboratoire du Dre Sarfati en collaboration avec le Dr Senécal, un modèle de souris expérimental induit par l’immunisation de cellules dendritiques (DCs) chargées de peptides de la protéine topoisomérase I (TOPOIA et TOPOIB). Dans le but de caractériser ce modèle murin et d’établir un profil immunitaire, j’ai concentré mes analyses principalement sur les caractéristiques de la SSc telles que la fibrose, l’inflammation, l’hyper-γ-globulinémie polyclonale, la vasculopathie ainsi que de l’expression de cytokines. Brièvement, l’immunisation de souris avec les DCs chargées avec la topoisomérase I (TOPOI) a induit l’inflammation pulmonaire et cutanée, en plus de la fibrose sous forme diffuse (dcSSc). Les souris présentaient également des symptômes de la vasculopathie ainsi que des taux élevés d’anticorps polyclonaux. Les résultats démontraient que les peptides TOPOIA étaient efficaces dans l’induction de la fibrose et de la réponse inflammatoire alors que les peptides TOPOIB étaient surtout impliqués dans la fibrose cutanée. En plus de nos résultats, les observations préliminaires sur le profil de cytokines tissulaires suggéraient que ce modèle pourrait remplacer ou complémenter les autres modèles animaux de SSc.