983 resultados para Legendre Polynomial Dipole Moment Generating Function


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Inhibition of local host immune reactions is one mechanism contributing to tumor progression. To determine if alterations in local immune functioning occur during colon carcinogenesis, a model mucosal immune response, type I hypersensitivity against the intestinal parasite Trichinella spiralis, was first characterized in normal mice and then examined during experimental colon carcinogenesis. Segments of sensitized colon mounted in Ussing chambers and challenged with T. spiralis-derived antigen resulted in a rise in short-circuit current ($\rm\Delta I\sb{sc}$) that was antigen-specific and inhibited by furosemide, implicating epithelial Cl$\sp-$ secretion as the ionic mechanism. The immune-regulated Cl$\sp-$ secretion by colonic epithelial cells required the presence of mast cells with surface IgE. Inhibition of potential anaphylactic mediators with various pharmacological agents in vitro implicated prostaglandins and leukotrienes as the principal mediators of the antigen-induced $\rm\Delta I\sb{sc}$, with 5-hydroxytryptamine also playing a role. Distal colon from immune mice fed an aspirin-containing diet (800 mg/kg powdered diet) ad libitum for 6 wk had a decreased response to antigen, confirming the major role of prostaglandins in generating the colonic I$\sb{\rm sc}$. To determine the effects of early stages of colon carcinogenesis on this mucosal immune response, mice were immunized with T. spiralis 1 day after or 8 wk prior to the first of 6 weekly injections of the procarcinogen 1,2-dimethylhydrazine (DMH). Responsiveness to antigenic challenge was suppressed in the distal colon 4-6 wk after the final injection of DMH. One injection of DMH was not sufficient to inhibit antigen responsiveness. The colonic epithelium remained sensitive to direct stimulation by exogenous Cl$\sp-$ secretagogues. Decreased antigen-induced $\rm\Delta I\sb{sc}$ in the distal colon was not due to systemic immune suppression by DMH, as the proximal colon and jejunum maintained responsiveness to antigen. Also, rejection of a secondary T. spiralis infection from the small intestine was not altered. Tumors eventually developed 25-30 wk after the final injection of DMH only in the distal portions of the colon. These results suggest that early stages of DMH-induced colon carcinogenesis manipulate the microenvironment such that mucosal immune function, as measured by immune-regulated Cl$\sp-$ secretion, is suppressed in the distal colon, but not in other regions of the gut. Future elucidation of the mechanisms by which this localized inhibition of immune-mediated ion transport occurs may provide possible clues to the microenvironmental changes necessary for tumor progression in the distal colon. ^

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We derive explicit lower and upper bounds for the probability generating functional of a stationary locally stable Gibbs point process, which can be applied to summary statistics such as the F function. For pairwise interaction processes we obtain further estimates for the G and K functions, the intensity, and higher-order correlation functions. The proof of the main result is based on Stein's method for Poisson point process approximation.

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The 3' cleavage generating non-polyadenylated animal histone mRNAs depends on the base pairing between U7 snRNA and a conserved histone pre-mRNA downstream element. This interaction is enhanced by a 100 kDa zinc finger protein (ZFP100) that forms a bridge between an RNA hairpin element upstream of the processing site and the U7 small nuclear ribonucleoprotein (snRNP). The N-terminus of Lsm11, a U7-specific Sm-like protein, was shown to be crucial for histone RNA processing and to bind ZFP100. By further analysing these two functions of Lsm11, we find that Lsm11 and ZFP100 can undergo two interactions, i.e. between the Lsm11 N-terminus and the zinc finger repeats of ZFP100, and between the N-terminus of ZFP100 and the Sm domain of Lsm11, respectively. Both interactions are not specific for the two proteins in vitro, but the second interaction is sufficient for a specific recognition of the U7 snRNP by ZFP100 in cell extracts. Furthermore, clustered point mutations in three phylogenetically conserved regions of the Lsm11 N-terminus impair or abolish histone RNA processing. As these mutations have no effect on the two interactions with ZFP100, these protein regions must play other roles in histone RNA processing, e.g. by contacting the pre-mRNA or additional processing factors.

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Human behavior appears to be regulated in part by noradrenergic transmission since antidepressant drugs modify the number and function of (beta)-adrenergic receptors in the central nervous system. Affective illness is also known to be associated with the endocrine system, particularly the hypothalamic-pituitary-adrenal axis. The aim of the present study was to determine whether hormones, in particular adrencorticotrophin (ACTH) and corticosterone, may influence behavior by regulating brain noradrenergic receptor function.^ Chronic treatment with ACTH accelerated the increase or decrease in rat brain (beta)-adrenergic receptor number induced by a lesion of the dorsal noradrenergic bundle or treatment with the antidepressant imipramine. Chronic administration of ACTH alone had no effect on (beta)-receptor number although it reduced norepinephrine stimulated cyclic AMP accumulation in brain slices. Treatment with imipramine also reduced the cyclic AMP response to norepinephrine but was accompanied by a decrease in (beta)-adrenergic receptor number. Both the imipramine and ACTH treatments reduced the affinity of (beta)-adrenergic receptors for norepinephrine, but only the antidepressant modified the potency of the neurotransmitter to stimulate second messenger production. Neither ACTH nor imipramine treatment altered Gpp(NH)p- or fluoride-stimulated adenylate cyclase, cyclic AMP, cyclic GMP, or cyclic GMP-stimulated cyclic AMP phosphodiesterase, or the activity of the guanine nucleotide binding protein (Gs). These findings suggested that post-receptor components of the cyclic nucleotide generating system are not influenced by the hormone or antidepressant. This conclusion was verified by the finding that neither treatment altered adenosine-stimulated cyclic AMP accumulation in brain tissue.^ A detailed examination of the (alpha)- and (beta)-adrenergic receptor components of norepinephrine-stimulated cyclic AMP production revealed that ACTH, but not imipramine, administration reduced the contribution of the (alpha)-receptor mediated response. Like ACTH treatment, corticosterone diminished the (alpha)-adrenergic component indicating that adrenal steroids probably mediate the neurochemical responses to ACTH administration. The data indicate that adrenal steroids and antidepressants decrease noradrenergic receptor function by selectively modifying the (alpha)- and (beta)-receptor components. The functional similarity in the action of the steroid and antidepressants suggests that adrenal hormones normally contribute to the maintenance of receptor systems which regulate affective behavior in man. ^

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Cardiovascular disease (CVD) is the leading cause of death in the United States. One manifestation of CVD known to increase mortality is an enlarged, or hypertrophic heart. Hypertrophic cardiomyocytes adapt to increased contractile demand at the genetic level with a re-emergence of the fetal gene program and a downregulation of fatty acid oxidation genes with concomitant increased reliance on glucose-based metabolism. To understand the transcriptional regulatory pathways that implement hypertrophic directives we analyzed the upstream promoter region of the muscle specific isoform of the nuclear-encoded mitochondrial gene, carnitine palmitoyltransferase-1β (CPT-1β) in cultured rat neonatal cardiac myocytes. This enzyme catalyzes the rate-limiting step of fatty acid entry into β-oxidation and is downregulated in cardiac hypertrophy and failure, making it an attractive model for the study of hypertrophic gene regulation and metabolic adaptations. We demonstrate that the muscle-enriched transcription factors GATA-4 and SRF synergistically activate CPT-1β; moreover, DNA binding to cognate sites and intact protein structure are required. This mechanism coordinates upregulation of energy generating processes with activation of the energy consuming contractile promoter for cardiac α-actin. We hypothesized that fatty acid or glucose responsive transcription factors may also regulate CPT-1β. Oleate weakly stimulates CPT-1β activity; in contrast, the glucose responsive Upstream Stimulatory Factors (USF) dramatically depresses the CPT-1β reporter. USF regulates CPT-1β through a novel physical interaction with the cofactor PGC-1 and abrogation of MEF2A/PGC-1 synergistic stimulation. In this way, USF can inversely regulate metabolic gene programs and may play a role in the shift of metabolic substrate preference seen in hypertrophy. Failing hearts have elevated expression of the nuclear hormone receptor COUP-TF. We report that COUP-TF significantly suppresses reporter transcription independent of DNA binding and specific interactions with GATA-4, Nkx2.5 or USF. In summary, CPT-1β transcriptional regulation integrates mitochondrial gene expression with two essential cardiac functions: contraction and metabolic substrate oxidation. ^

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A major goal of chemotherapy is to selectively kill cancer cells while minimizing toxicity to normal cells. Identifying biological differences between cancer and normal cells is essential in designing new strategies to improve therapeutic selectivity. Superoxide dismutases (SOD) are crucial antioxidant enzymes required for the elimination of superoxide (O2·− ), a free radical produced during normal cellular metabolism. Previous studies in our laboratory demonstrated that 2-methoxyestradiol (2-ME), an estradiol derivative, inhibits the function of SOD and selectively kills human leukemia cells without exhibiting significant cytotoxicity in normal lymphocytes. The present work was initiated to examine the biochemical basis for the selective anticancer activity of 2-ME. Investigations using two-parameter flow cytometric analyses and ROS scavengers established that O2·− is a primary and essential mediator of 2-ME-induced apoptosis in cancer cells. In addition, experiments using SOD overexpression vectors and SOD knockout cells found that SOD is a critical target of 2-ME. Importantly, the administration of 2-ME resulted in the selective accumulation of O 2·− and apoptosis in leukemia and ovarian cancer cells. The preferential activity of 2-ME was found to be due to increased intrinsic oxidative stress in these cancer cells versus their normal counterparts. This intrinsic oxidative stress was associated with the upregulation of the antioxidant enzymes SOD and catalase as a mechanism to cope with the increase in ROS. Furthermore, oxygen consumption experiments revealed that normal lymphocytes decrease their respiration rate in response to 2-ME-induced oxidative stress, while human leukemia cells seem to lack this regulatory mechanism. This leads to an uncontrolled production of O2·−, severe accumulation of ROS, and ultimately ROS-mediated apoptosis in leukemia cells treated with 2-ME. The biochemical differences between cancer and normal cells identified here provide a basis for the development of drug combination strategies using 2-ME with other ROS-generating agents to enhance anticancer activity. The effectiveness of such a combination strategy in killing cancer cells was demonstrated by the use of 2-ME with agents/modalities such as ionizing radiation and doxorubicin. Collectively, the data presented here strongly suggests that 2-ME may have important clinical implications for the selective killing of cancer cells. ^

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The complement system functions as a major effector for both the innate and adaptive immune response. Activation of the complement cascade by either the classical, alternative, or lectin pathway promotes the proteolysis of C3 and C5 thereby generating C3a and C5a. Referred to as anaphylatoxins, the C3a and C5a peptides mediate biological effects upon binding to their respective receptors; C3a binds to the C3a receptor (C3aR) while C5a binds to the C5a receptor (C5aR, CD88). Both C3a and C5a are known for their broad proinflammatory effects. Elevated levels of both peptides have been isolated from patients with a variety of inflammatory diseases such as COPD, asthma, RA, SLE, and sepsis. Recent studies suggest that C5a is a critical component in the acquired neutrophil dysfunction, coagulopathy, and progressive multi-organ dysfunction characteristic of sepsis. The primary hypothesis of this dissertation was that preventing C3a-C3aR and C5a-C5aR mediated pro-inflammatory effects would improve survival in endotoxic, bacteremic and septic shock. To test this hypothesis, the murine C3aR and C5aR genes were disrupted. Following disruption of both the C3aR and C5aR genes, no abnormalities were identified other than the absence of their respective mRNA and protein. In models of both endotoxic and bacteremic shock, C3aR deficient mice suffered increased mortality when compared to their wild type littermates. C3aR deficient mice also had elevated circulating IL-1β levels. Using a model of sepsis, C3aR deficient mice had a higher circulating concentration of IL-6 and decreased peritoneal inflammatory infiltration. While these results were unexpected, they support an emerging role for C3a in immunomodulation. In contrast, following endotoxic or bacteremic shock, C5aR deficient mice experienced increased survival, less hemoconcentration and less thrombocytopenia. It was later determined that C5a mediated histamine release significantly contributes to host morbidity and mortality in bacteremic shock. These studies provide evidence that C5a functions primarily as a proinflammatory molecule in models of endotoxic and bacteremic shock. In the same models, C3a-C3aR interactions suppress the inflammatory response and protect the host. Collectively, these results present in vivo evidence that C3a and C5a have divergent biological functions. ^

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En este trabajo examinaremos la función mediadora de los líderes políticos locales en la construcción de los cimientos de la identificación con el peronismo bonaerense. Éstos, sin ser colaboradores directos de Perón, desempeñaron un rol fundamental a la hora de generarle fuerza política y prestigio al peronismo en localidades "extracéntricas", alejadas de los centros de poder e insertas en contextos rurales. ¿Es posible denominarlos como la "tercera línea" de liderazgo peronista? Para responder esta incógnita, exploraremos desde una perspectiva microanalítica las trayectorias y creciente participación en la esfera política de algunas figuras que les permitieron, en mayor o menor grado, convertirse en referentes políticos locales y constituir bases sociales. Nos preguntamos cuál era el fundamento de legitimidad de su poder y cuál era el margen de autonomía con el que contaban respecto a las instancias de poder provincial y nacional.

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En este trabajo examinaremos la función mediadora de los líderes políticos locales en la construcción de los cimientos de la identificación con el peronismo bonaerense. Éstos, sin ser colaboradores directos de Perón, desempeñaron un rol fundamental a la hora de generarle fuerza política y prestigio al peronismo en localidades "extracéntricas", alejadas de los centros de poder e insertas en contextos rurales. ¿Es posible denominarlos como la "tercera línea" de liderazgo peronista? Para responder esta incógnita, exploraremos desde una perspectiva microanalítica las trayectorias y creciente participación en la esfera política de algunas figuras que les permitieron, en mayor o menor grado, convertirse en referentes políticos locales y constituir bases sociales. Nos preguntamos cuál era el fundamento de legitimidad de su poder y cuál era el margen de autonomía con el que contaban respecto a las instancias de poder provincial y nacional.

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En este trabajo examinaremos la función mediadora de los líderes políticos locales en la construcción de los cimientos de la identificación con el peronismo bonaerense. Éstos, sin ser colaboradores directos de Perón, desempeñaron un rol fundamental a la hora de generarle fuerza política y prestigio al peronismo en localidades "extracéntricas", alejadas de los centros de poder e insertas en contextos rurales. ¿Es posible denominarlos como la "tercera línea" de liderazgo peronista? Para responder esta incógnita, exploraremos desde una perspectiva microanalítica las trayectorias y creciente participación en la esfera política de algunas figuras que les permitieron, en mayor o menor grado, convertirse en referentes políticos locales y constituir bases sociales. Nos preguntamos cuál era el fundamento de legitimidad de su poder y cuál era el margen de autonomía con el que contaban respecto a las instancias de poder provincial y nacional.

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La Tesis decodifica una selección de veinte proyectos representativos de Sejima-SANAA, desde su primer proyecto construido, la Casa Platform I, 1987, hasta el Centro Rolex, 2010, año en que Sejima y Nishizawa –SANAA- reciben el Premio Pritzker. De los veinte proyectos once son de Sejima: Casa Platform I, Casa Platform II, Residencia de Mujeres, Casa N, Pachinco Parlor I, Villa en el Bosque, Comisaría en Chofu, Casa Y, Apartamentos en Gifu, Edificio de equipamientos en la Expo Tokio 96, Pachinko Parlor III; y nueve de SANAA: edificio Multimedia en Oogaki, estudio de viviendas metropolitanas,Park Café en Koga, De Kunstlinie en Almere, Museo de Kanazawa, Pabellón de Toledo, Escuela de Zollverein, Casa Flor y Centro Rolex. La decodificación lee la obra de Sejima-SANAA a la inversa para ‘reconstruir’, en un ejercicio de simulación ficticia, una versión verosímil y coherente de los que podrían haber sido sus procesos proyectuales; podrían, porque los verdaderos son imposibles de dilucidar. Los que se proponen se pretenden exclusivamente verosímiles y plausibles. Con ello se pretende contribuir al entendimiento y comprensión de la arquitectura de Sejima-SANAA y, tangencialmente y en menor medida, a la teoría sobre el ejercicio proyectual arquitectónico. La decodificación se centra en dos aspectos concretos: la forma arquitectónica y el papel proyectual de la estructura portante. Ambas decodificaciones se extienden inevitablemente a otros aspectos relacionados, como, por ejemplo, la naturaleza del espacio arquitectónico. El procedimiento de investigación partió de una descripción objetiva y pormenorizada de los significantes formales y estructurales de cada proyecto desde su propia configuración física y geométrica. Esa descripción ‘objetiva’, llevada al límite, permitió que afloraran estructuras conceptuales y lógicas subyacentes de cada proyecto. Unida a interpretación crítica, –mediante su relación y confrontación con otras arquitecturas y otros modos de hacer conocidos- permitió trazar la reconstitución ficticia que persigue la decodificación. Ese trabajo se materializó en veinte ensayos críticos y se acompañó de un conjunto de otros textos sobre temas sugeridos o reclamados por el proceso de investigación. El conjunto de todos esos textos constituye el material de trabajo de la tesis. A partir de ahí, con una visión de conjunto, la tesis identifica una trayectoria de estrategias formales y una trayectoria de estrategias proyectuales relacionadas con lo portante. Juntas conforman el grueso de la tesis que se expone en los cuatro capítulos centrales. Los precede un capítulo introductorio que expone el recorrido biográfico de K. Sejima y la trayectoria profesional de Sejima-SANAA; y los siguen de unos textos transversales sobre forma, lugar y espacio. La tesis termina con una síntesis de sus conclusiones. Las estrategias formales se exponen en tres capítulos. El primero, ‘Primeras estrategias formales’ agrupa proyectos de la primera etapa de Sejima. El segundo capítulo está dedicado enteramente al proyecto de los apartamentos en Gifu, 1994-98, que según esta tesis, supuso un importante punto de inflexión en la trayectoria de Sejima; tanto el tercer capítulo lleva por nombre ‘Estrategias formales después de Gifu’ y recoge los proyectos que le siguieron. Las ‘Primeras estrategias formales’, varias y balbucientes, se mueven en general en torno a dos modos o procedimientos de composición, bien conocidos: por partes y sistemático. Éste última inicia en la trayectoria de SANAA un aspecto que va a ser relevante de aquí en adelante: entender el proyecto como propuesta genérica en la que, más allá de su realidad específica y tangible, subyace una lógica, en cada proyecto la suya, extrapolable a otros lugares, otras dimensiones, incluso otros programas: cada proyecto podría dar lugar a otros proyectos de la misma familia. La composición sistemática incluye, entre otros, la Casa Platform II, basada en la definición de un elemento constructivo, y la formulación de unas leyes de repetición y de posibles modos de agrupación. Incluye también la Residencia de Mujeres Saishunkan Seiyaku- proyecto que lanzó a Sejima a la fama internacional-, que también sería un sistema, pero distinto: basado en la repetición regular de una serie de elementos a lo largo de una directriz generando un hipotético contenedor infinito del que el proyecto sería tan solo un fragmento. La estrategia formal del edificio de Gifu ahondaría en la voluntad genérica del proyecto, adoptando la lógica de un juego. El proyecto sería una partida del juego, pero no la única posible, podrían jugarse otras. Esta hipótesis del juego está verificada en ‘El Juego de Gifu’ que - tras formular el juego identificando sus elementos (tablero y fichas), reglas y procedimientos- juega una partida: la que habría dado lugar al edificio proyectado por Sejima. Gifu extiende el concepto de ‘repetir’ un elemento constructivo a la de repetir un patrón espacial, lo que conlleva: la desvinculación entre forma y función; y un nuevo concepto de flexibilidad, que deja de referirse al uso flexible del edificio construido para pertenecer al momento proyectual en que se asignan funciones específicas a los patrones espaciales. Esta tesis propone que esa asignación de funciones sería uno de los últimos eslabones del proceso proyectual, algo opuesto a la premisa moderna de “la forma sigue a la función”. Las estrategias formales ‘Después de Gifu’ tienen también lógicas de juego, pero cada estrategia responde a un juego distinto, como dejan entrever sus nombres: ‘Tableros de Juego’, que con distintos grados de madurez estaría presente en varios proyectos; ‘Elementos de Catálogo’ en el Museo de Kanazawa; ‘Forma apriorística’, en la Casa Flor y ‘Repetición de una situación topológica’, en el Centro Rolex. Todas esas estrategias, o juegos, mantienen aspectos comunes relativos a la forma arquitectónica, precisamente los aspectos Gifu: la repetición aplicada al patrón espacial, y lo que conlleva: desvinculación entre forma y función y la nueva acepción de flexibilidad. ‘Tableros de Juego’ consiste en configurar cada sistema de proyecto (estructura, cerramientos, particiones y mobiliario) eligiendo elementos ofrecidos por una geometría de base, en cada proyecto la suya, en general reticular: intersecciones, líneas, módulos. Cada sistema se configura, en principio, sin relación de subordinación con cualquiera de los demás; cuando esa subordinación es ineludible, el juego determina que el sistema portante no puede materializar el orden geométrico de base, lo que se traduce en que no ejerce el papel dominante. Por lo tanto, ‘Tableros de Juego’ transgrede la lógica de la planta libre moderna: la estructura ni refleja ni revela el orden de base y los sistemas no respetan las relaciones de subordinación jerárquica y encadenada que aquella determinaba. Esta estrategia de ‘Tableros de juego’ deriva en soluciones y proyectos formales muy distintos: los proyectos de Oogaki y Park Café, que presentarían ‘Tableros de Juego’ incipientes; De Kunstlinie en Almere y la Escuela de Zollverein, que presentarían una consolidación de esta estrategia; y el Pabellón de Vidrio de Toledo que resultaría de la subversión de la estrategia. Este último proyecto, además, lleva el concepto de repetición más allá del elemento constructivo y del patrón espacial (que en este caso tiene forma de burbuja) parar acabar afectando a la propia experiencia del espectador, que esté donde esté, siempre tiene la sensación de estar en el mismo sitio. Esta tesis denomina a ese espacio repetitivo como ‘espacio mantra’. La estrategia ‘Elementos de Catálogo’ se ilustra con el Museo de Kanazawa. Su lógica parte de la definición de una serie de elementos, muy pocos, y se basa en el ingente número de posibles combinaciones entre sí. Gifu habría anunciado el catalogo de elementos en la caracterización de sus patrones espaciales. La estrategia ‘Forma Apriorística’ se ilustra con la Casa Flor. La decisión sobre el tipo de forma -en este caso la de una ameba- estaría al principio del proceso proyectual, lo que no quiere decir que sea una forma arbitraria: la forma de la ameba lleva implícita la repetición de un patrón espacial (el seudópodo) y una apoteosis del concepto de repetición que, alcanzando la experiencia espacial, da lugar a un espacio repetitivo o mantra. El ‘Espacio Mantra’ es uno de los leitmotivs, que se emplean como argumento en la última estrategia formal que la Tesis decodifica: el Centro Rolex. Con respecto a la estructura portante, la tesis identifica y traza una trayectoria de cinco estrategias proyectuales: preeminencia, ocultación, disolución, desaparición y desvirtuación. --Ocultación, reduce el papel dominante de la estructura. Al principio es una ocultación literal, casi un tapado de los elementos estructurales, como en Gifu; luego se hace más sofisticada, como la ocultación por camuflaje o la paradójica ocultación por multiplicación de Park Café. --La disolución merma la condición dominante de la estructura que en lugar de configurarse como sistema unitario u homogéneo se fragmenta en varios subsistemas. --La desaparición se refiere a estructuras que desaparecen como sistemas propios y autónomos, a proyectos en los que la función portante es desempeñada por otros sistemas como el de las particiones. La desaparición culmina con la Casa Flor, cuyo perímetro ejerce la función portante y además es transparente, está desmaterializado: la estructura se ha hecho invisible, ha desaparecido. --La desvirtuación se refiere a estructuras que sí se presentan como sistemas propios y autónomos, pero dejan de tener un papel preeminente por cuanto no materializan el orden de base: esta estrategia es correlativa a la estrategia formal ‘Tableros de juego’. Las conclusiones de la tesis están en la propia organización de la tesis: la identificación de las estrategias. Aún así, y como epílogos, se exponen seis. Las dos primeras subrayan el hilo conductor del trabajo realizado, que radica en la cualidad genérica de las estrategias proyectuales en Sejima-SANAA. Las cuatro siguientes dilucidan hasta qué punto hay, en sus proyectos, rasgos o significantes formales y/o estructurales que sean a su vez señales características del panorama arquitectónico contemporáneo; y plantean la pregunta estrella: ¿hay algunos que, apuntando más lejos, supongan aportaciones originales? --Como aportaciones originales la tesis destaca: la identificación entre el ideal genérico y proyecto concreto; y la propuesta de un espacio nuevo, híbrido, una suerte de estadio intermedio entre el espacio subdividido y compartimentado de la tradición y el continuo moderno. --Como síntomas de contemporaneidad se destacan: respecto de la forma, la traslación de la especificidad formal de la parte al conjunto; y respecto de la estructura, la tendencia contemporánea a hacer estructuras cada vez más ligeras y livianas, que tienden a lo evanescente. Ésta última, la tendencia al evanescencia estructural, podría tener la condición de aportación original, no en vano la desaparición de la estructura lleva la evanescencia hacia sus últimas consecuencias, y en el caso de estructuras con presencia física, hace que dejen de ser el sistema ordenador orquestador del proceso proyectual. ABSTRACT The Thesis decodes a selection of twenty representative Sejima-SANAA projects, from the first one built, the Platform I House in 1987, to the Rolex Center in 2010, year in which Sejima and Nishizawa –SANAA- received the Pritzker Prize. Eleven projects are from Sejima: Platform I, Platform II, Saishunkan Seiyaku Women´s Dormitory, N- House, Pachinco Parlor I, Villa in the Forest, Policy Box at Chofu Station, Y-House, Gifu Kitigata Apartment, World City Expo ´96 Facilities Building, Pachinko Parlor III; and nine from SANAA: Multimedia Workshop in Ogaki, Metropolitan Housing Studies, Park Café in Koga, De Kunstlinie in Almere, Kanazawa Museum, Glass Pavilion at the Toledo Museum of Art, Zollverein School, Flower House and the Rolex Center. This decoding reads the Sejima-SANAA’s projects inversely aiming ‘to reconstruct', in a fictitious simulation exercise, a likely and coherent version of what her/their projectual processes ‘could’ have been; ‘could’, because the true ones are impossible to explain. The ones proposed here pretend only to be likely and reasonable. By so doing the Thesis tries to contribute to the understanding and comprehension of Sejima-SANAA architecture and, tangentially and to a lesser extent, to the theory of architectural projects exercise. Decoding centers in two specific aspects: architectural form, and projectual role of the load bearing structure. Both decodes inevitably extend to other related aspects such as, for example, the nature of space. The research procedure begun by carrying out an objective and detailed description of the formal and structural signifiers of each project; looking at them from their physical and geometric configuration. Taken to the limit, the ‘objective’ descriptions allowed the conceptual structures and underlying logics of each project to arise. Together with critical interpretations, which related and confronted them with other architectures and well-known projectual working ways, it became possible to outline and trace the intended fictitious reconstruction decodes. The descriptive analytical work materialized in twenty critical essays, and was accompanied by a set of other essays on subjects suggested or demanded by the research process. Together, all those texts were the material basis on which thesis work was built. Looking at the whole and taking it from there, the thesis identifies two related projectual trajectories: a trajectory of formal strategies and a trajectory of strategies having to do with structural systems and components. Both, together, constitute the bulk of the thesis, as presented in the four central chapters. Preceding them there is an introductory chapter outlining the biographical path of Kazuyo Sejima and the professional trajectory of Sejima-SANAA. And following them there is another one containing transversal texts on form, place and space. The thesis ends with a synthesis on conclusions. The formal strategies are displayed in three chapters. The first one, `Early formal strategies' groups the first phase projects by Sejima. The second one, ‘Formal strategies of Gifu’s paradigm’, is entirely dedicated to the Gifu apartments project, 1994-98, which according to this thesis meant an important inflexion point in Sejima’s trajectory; so much so that the third chapter is named `Formal strategies after Gifu' and gathers the selected projects that followed it. The ‘Early formal strategies', diverse and tentative, move in general around two well-known projectual composition methods ‘composition by parts’, and ‘systematic composition’. This last one –systematic composition- begins and leads in SANAA’s trajectory an aspect which will remain relevant from here on: the understanding of the project as if it were an specific instance of a generic proposal in which -below and beyond the project tangible reality- there lays a logic that could be applicable at other places, for other dimensions, even with other programs; from each project, other projects of the same family could rise. The set of projects using this systematic composition method include, among others, the ‘Platform II House, based on the definition of a constructive element and of rules having to do with its replicas and their possible groupings. It also includes the Saishunkan Seiyaku Women Residence -project that launched Sejima to international fame- that could also be seen as a system, but of a different kind: a system based on the regular repetition of a series of elements along a directive line, thus generating a hypothetical infinite container of which the project would be only a fragment. The formal strategy of the Gifu apartments building would push further towards the generic project concept, adopting the logic of a game. The project would be a bout, a round, one play…, but not the only possible one; others could be played. The thesis confirms this game hypothesis -after having formulated `The Game of Gifu' and identified its elements (board, chips, rules and procedures)- playing the one play from which the building as projected by Sejima would have raised. Gifu extends the concept of ‘repeating a constructive element’ to that of ‘repeating a space pattern element’, and to what it implies: the decoupling of form and function, leading to a new concept of flexibility that no longer refers to the flexible use of the constructed building but to the projectual moment at which the specific functions are assigned to the space patterns. This thesis proposes that this allocation of functions would be one of the last steps in projectual process, quite opposite from the modern premise: “form follows function”. The Formal strategies after Gifu do also have a game logic; but, as their names reveal, each strategy responds to a different game: ‘Game Boards’, present with different maturity levels in several projects; ‘Elements from a Catalogue’, in the Kanazawa Museum; ‘Aprioristic Form’, in the Flower House; and ‘Repetition of a topologic situation', in the Rolex Center. All of these strategies, or games, maintain common aspects having to do with architectural form; aspects that were already present, precisely, in Gifu: repetition of space pattern units, uncoupling of form and function, and a new meaning of flexibility. -`Game Boards’ consists on setting up a base geometry -each project his, generally reticular- and give form to each project system (structure, closings, partitions and furniture) by choosing elements -intersections, lines, modules- it offers. Each project system is formed, in principle, with no subordinated relation with any of the others; when subordination is unavoidable, the game rules determine that the load bearing structural system may not be the one to materialize the base geometric order, which means that it does not exert the dominant role. Therefore, ‘Game Boards' transgresses the Modern logic, because the structure neither reflects nor reveals the base order, and because the systems do not respect any of the hierarchic and chained subordination relations that the ‘free plan’ called for. ‘Game Boards' leads to quite different solutions and formal projects: the Oogaki and Park Coffee projects show incipient Game Boards; The Almere Kunstlinie and the Zollverein School present consolidations of this strategy; and the Toledo’s Glass Pavilion results from subverting the strategy. In addition, the Toledo project takes the repetition concept beyond that of using a constructive element and a space pattern element (in this case with a bubble form) to end up affecting the personal experience of the spectator, who, wherever he is, feels to always be in the same place. This thesis denominates that repetitive space as ‘Mantra space '. -‘Elements from a Catalogue’ is shown with the Kanazawa Museum. Its logic starts from the definition of a series of elements, very few, and it is based on the huge number of possible combinations among them. The ‘Elements from a Catalogue’ approach was announced in the Gifu project when characterizing its space pattern elements. -Aprioristic Form' is illustrated by the Flower House. The decision on the type of form -in this case the form of an amoeba- would be the beginning of the projectual process, but it does not mean it is arbitrary form: the amoeba form implies repeating a space pattern (pseudopodia) and an apotheosis of the repetition concept: embracing the space experience, it gives rise to a repetitive or mantra space. ‘Mantra Space’ is one of leitmotivs used as an argument in the last formal strategy Thesis decodes: the Rolex Center. With respect to the ‘Projectual strategies of the load bearing structure’, the thesis finds and traces a trajectory of five projectual strategies: ‘preeminence, concealment, dissolution, disappearance and desvirtuación’. --Preeminence is present in Sejima’s first works in which she resorts to structures which have a dominant preeminent role in the project in so far as they impersonate the greater scale and/or materialize the base geometric order. In later works that preeminence will be inverted, the projects aiming towards its opposite: lighter, slighter, smaller structures. -Concealment reduces the dominant role of the structure. At the outset concealment is literal, almost hiding the structural elements, as in Gifu; soon it will become more sophisticated, such as the concealment by camouflage or the paradoxical concealment by multiplication in the Koga Park Café. -Dissolution diminishes the dominant condition of the structure: instead of its’ being configured as unitary or homogenous system is fragmented in several subsystems. -Disappearance talks about structures that fade away as self referred and independent systems; projects in which the load bearing function is carried out by other systems such as the set of partitions. Disappearance reaches its zenith at the Flower House, whose perimeter functions structurally being, in addition, transparent, immaterial: its structure has become invisible, has disappeared. -Desvirtuación talks about structures that do appear like independent self-systems, but which that do not longer have a preeminent paper, inasmuch as they do not materialize the base order. This strategy correlates with the ‘Game Boards’ formal strategy. The thesis conclusions are show by the organization of the thesis itself: its identification of the different strategies. Even so, as epilogues, the thesis exposes six ‘Conclusions’. The first two emphasize the leading thread of the work done, rooted in the generic quality of the Sejima-SANAA projectual strategies. The following four expound to what extent their projects show features, or formal and/or structural signifiers, which also are or can be read as characteristic signals of the contemporary architectonic panorama, and raise the key question: aiming farther, may some of them be taken as original contributions? -As original contributions the conclusions highlight: the identification between the generic ideal and the concrete project; and the proposal of a new, hybrid space, kind of an intermediate stage between the traditional subdivided compartmented space and the continuous modern. -As symptoms of contemporaneousness: in relation to the form it highlights the transferring of the formal specificity from the part to the whole; and in relation to the structure, it underscore the contemporary tendency towards lighter and growingly slimmer structures, tending to the evanescent. This last one, the tendency towards structural evanescence, could have condition of being an original contribution, not in vain it carries the structural disappearance towards its last consequences; and in the case of structures with physical presence, it makes them to cease being the ordering system orchestrating the projectual process.

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Many computer vision and human-computer interaction applications developed in recent years need evaluating complex and continuous mathematical functions as an essential step toward proper operation. However, rigorous evaluation of this kind of functions often implies a very high computational cost, unacceptable in real-time applications. To alleviate this problem, functions are commonly approximated by simpler piecewise-polynomial representations. Following this idea, we propose a novel, efficient, and practical technique to evaluate complex and continuous functions using a nearly optimal design of two types of piecewise linear approximations in the case of a large budget of evaluation subintervals. To this end, we develop a thorough error analysis that yields asymptotically tight bounds to accurately quantify the approximation performance of both representations. It provides an improvement upon previous error estimates and allows the user to control the trade-off between the approximation error and the number of evaluation subintervals. To guarantee real-time operation, the method is suitable for, but not limited to, an efficient implementation in modern Graphics Processing Units (GPUs), where it outperforms previous alternative approaches by exploiting the fixed-function interpolation routines present in their texture units. The proposed technique is a perfect match for any application requiring the evaluation of continuous functions, we have measured in detail its quality and efficiency on several functions, and, in particular, the Gaussian function because it is extensively used in many areas of computer vision and cybernetics, and it is expensive to evaluate.

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Graphs of second harmonic generation coefficients and electro-optic coefficients (measured by ellipsometry, attenuated total reflection, and two-slit interference modulation) as a function of chromophore number density (chromophore loading) are experimentally observed to exhibit maxima for polymers containing chromophores characterized by large dipole moments and polarizabilities. Modified London theory is used to demonstrated that this behavior can be attributed to the competition of chromophore-applied electric field and chromophore–chromophore electrostatic interactions. The comparison of theoretical and experimental data explains why the promise of exceptional macroscopic second-order optical nonlinearity predicted for organic materials has not been realized and suggests routes for circumventing current limitations to large optical nonlinearity. The results also suggest extensions of measurement and theoretical methods to achieve an improved understanding of intermolecular interactions in condensed phase materials including materials prepared by sequential synthesis and block copolymer methods.

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Guanine nucleotide-binding proteins (G proteins) activate K+ conductances in cardiac atrial cells to slow heart rate and in neurons to decrease excitability. cDNAs encoding three isoforms of a G-protein-coupled, inwardly rectifying K+ channel (GIRK) have recently been cloned from cardiac (GIRK1/Kir 3.1) and brain cDNA libraries (GIRK2/Kir 3.2 and GIRK3/Kir 3.3). Here we report that GIRK2 but not GIRK3 can be activated by G protein subunits G beta 1 and G gamma 2 in Xenopus oocytes. Furthermore, when either GIRK3 or GIRK2 was coexpressed with GIRK1 and activated either by muscarinic receptors or by G beta gamma subunits, G-protein-mediated inward currents were increased by 5- to 40-fold. The single-channel conductance for GIRK1 plus GIRK2 coexpression was intermediate between those for GIRK1 alone and for GIRK2 alone, and voltage-jump kinetics for the coexpressed channels displayed new kinetic properties. On the other hand, coexpression of GIRK3 with GIRK2 suppressed the GIRK2 alone response. These studies suggest that formation of heteromultimers involving the several GIRKs is an important mechanism for generating diversity in expression level and function of neurotransmitter-coupled, inward rectifier K+ channels.

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Criado inicialmente com a função básica de proteção aos pés, o calçado tornou-se um objeto de desejo e um acessório essencial de moda. Entre 1950 a 2015, estima-se que a produção mundial passe de 2,5 bilhões de pares produzidos para 25 bilhões de pares por ano, crescimento bem maior do que a população mundial. O couro, principal matéria-prima para a confecção de calçados, caracteriza-se por gerar grandes quantidades de resíduos ao longo de toda a cadeia produtiva. Especificamente na indústria coureiro-calçadista, o problema concentra-se nos elevados volumes de resíduos gerados na atividade produtiva, podendo causar desperdícios e grandes volumes de resíduos a serem descartados, envolvendo, principalmente, questões financeiras e ambientais. Países como Alemanha e Estados Unidos possuem legislação específica sobre a gestão de resíduos desde os anos 1970. No Brasil, depois de mais de 20 anos de tramitação no Congresso Nacional, em 2010, foi instituída a Política Nacional de Resíduos Sólidos, que reúne princípios, objetivos, instrumentos, diretrizes e metas, que deverão ser adotados pelos governos nas esferas federal, estadual e municipal, bem como pelas empresas com vistas à gestão integrada e ao gerenciamento ambientalmente adequado dos resíduos sólidos. Dessa forma, o objetivo desta tese foi desenvolver um modelo de gestão de resíduos industriais para o setor calçadista de Franca-SP com vistas à Política Nacional de Resíduos Sólidos. O desenvolvimento do modelo teve como ponto de partida um estudo bibliográfico sobre o assunto e, na sequência, por intermédio de uma pesquisa aplicada, conseguiu-se, em um primeiro momento, analisar a situação atual para compreender o modelo de gestão de resíduos vigente e realizar uma pesquisa de diagnóstico dos resíduos industriais do setor. Tal pesquisa possibilitou verificar que atualmente, esses resíduos, são enviados em sua totalidade para aterros sanitários, possibilitou também sua quantificação e cálculos dos custos envolvidos para transporte e destinação. Na sequência, realizaram-se estudos sobre a viabilidade técnica e financeira para tratamento térmico desses resíduos e a busca de benchmark no setor. O estudo também proporcionou uma contribuição de caráter mais prático e/ou gerencial ao recomendar diretrizes para a elaboração de um plano de gestão integrada de resíduos industriais para o setor, e uma proposta de gestão compartilhada dos resíduos industriais entre a entidade de classe e as indústrias calçadistas, com vistas à eliminação de envio desses resíduos para aterros. Dessa forma, contribuiu também para a elaboração do Plano Municipal de Gestão Integrada de Resíduos Sólidos do município em questão. Nesse sentido, após as análises e desdobramentos das etapas anteriores, foi possível propor um modelo de gestão de resíduos industriais, bem como demonstrar sua viabilidade técnica e financeira. Tal modelo foi denominado \"Modelo de Equiparação de Custos com Eficiência Ambiental\".