Heteronuclear recoupling methods in solid-state NMR

This thesis is focused on the development of heteronuclear correlation methods in solid-state NMR spectroscopy, where the spatial dependence of the dipolar coupling is exploited to obtain structural and dynamical information in solids. Quantitative results on dipolar coupling constants are extracted by means of spinning sideband analysis in the indirect dimension of the two-dimensional experiments. The principles of sideband analysis were established and are currently widely used in the group of Prof. Spiess for the special case of homonuclear 1H double-quantum spectroscopy. The generalization of these principles to the heteronuclear case is presented, with special emphasis on naturally abundant 13C-1H systems. For proton spectroscopy in the solid state, line-narrowing is of particular importance, and is here achieved by very-fast sample rotation at the magic angle (MAS), with frequencies up to 35 kHz. Therefore, the heteronuclear dipolar couplings are suppressed and have to be recoupled in order to achieve an efficient excitation of the observed multiple-quantum modes. Heteronuclear recoupling is most straightforwardly accomplished by performing the known REDOR experiment, where pi-pulses are applied every half rotor period. This experiment was modified by the insertion of an additional spectroscopic dimension, such that heteronuclear multiple-quantum experiments can be carried out, which, as shown experimentally and theoretically, closely resemble homonuclear double-quantum experiments. Variants are presented which are well-suited for the recording of high-resolution 13C-1H shift correlation and spinning-sideband spectra, by means of which spatial proximities and quantitative dipolar coupling constants, respectively, of heteronuclear spin pairs can be determined. Spectral editing of 13C spectra is shown to be feasible with these techniques. Moreover, order phenomena and dynamics in columnar mesophases with 13C in natural abundance were investigated. Two further modifications of the REDOR concept allow the correlation of 13C with quadrupolar nuclei, such as 2H. The spectroscopic handling of these nuclei is challenging in that they cover large frequency ranges, and with the new experiments it is shown how the excitation problem can be tackled or circumvented altogether, respectively. As an example, one of the techniques is used for the identification of a yet unknown motional process of the H-bonded protons in the crystalline parts of poly(vinyl alcohol).

Optisch detektierte Magnetresonanz an NV-Zentren in Diamant

Die rasante Entwicklung der Computerindustrie durch die stetige Verkleinerung der Transistoren führt immer schneller zum Erreichen der Grenze der Si-Technologie, ab der die Tunnelprozesse in den Transistoren ihre weitere Verkleinerung und Erhöhung ihrer Dichte in den Prozessoren nicht mehr zulassen. Die Zukunft der Computertechnologie liegt in der Verarbeitung der Quanteninformation. Für die Entwicklung von Quantencomputern ist die Detektion und gezielte Manipulation einzelner Spins in Festkörpern von größter Bedeutung. Die Standardmethoden der Spindetektion, wie ESR, erlauben jedoch nur die Detektion von Spinensembles. Die Idee, die das Auslesen von einzelnen Spins ermöglich sollte, besteht darin, die Manipulation getrennt von der Detektion auszuführen.rn Bei dem NV−-Zentrum handelt es sich um eine spezielle Gitterfehlstelle im Diamant, die sich als einen atomaren, optisch auslesbaren Magnetfeldsensor benutzen lässt. Durch die Messung seiner Fluoreszenz sollte es möglich sein die Manipulation anderer, optisch nicht detektierbaren, “Dunkelspins“ in unmittelbarer Nähe des NV-Zentrums mittels der Spin-Spin-Kopplung zu detektieren. Das vorgeschlagene Modell des Quantencomputers basiert auf dem in SWCNT eingeschlossenen N@C60.Die Peapods, wie die Einheiten aus den in Kohlenstoffnanoröhre gepackten Fullerenen mit eingefangenem Stickstoff genannt werden, sollen die Grundlage für die Recheneinheiten eines wahren skalierbaren Quantencomputers bilden. Die in ihnen mit dem Stickstoff-Elektronenspin durchgeführten Rechnungen sollen mit den oberflächennahen NV-Zentren (von Diamantplatten), über denen sie positioniert sein sollen, optisch ausgelesen werden.rnrnDie vorliegende Arbeit hatte das primäre Ziel, die Kopplung der oberflächennahen NV-Einzelzentren an die optisch nicht detektierbaren Spins der Radikal-Moleküle auf der Diamantoberfläche mittels der ODMR-Kopplungsexperimente optisch zu detektieren und damit entscheidende Schritte auf dem Wege der Realisierung eines Quantenregisters zu tun.rn Es wurde ein sich im Entwicklungsstadium befindende ODMR-Setup wieder aufgebaut und seine bisherige Funktionsweise wurde an kommerziellen NV-Zentrum-reichen Nanodiamanten verifiziert. Im nächsten Schritt wurde die Effektivität und Weise der Messung an die Detektion und Manipulation der oberflächennah (< 7 nm Tiefe) implantieren NV-Einzelzenten in Diamantplatten angepasst.Ein sehr großer Teil der Arbeit, der hier nur bedingt beschrieben werden kann, bestand aus derrnAnpassung der existierenden Steuersoftware an die Problematik der praktischen Messung. Anschließend wurde die korrekte Funktion aller implementierten Pulssequenzen und anderer Software-Verbesserungen durch die Messung an oberflächennah implantierten NV-Einzelzentren verifiziert. Auch wurde der Messplatz um die zur Messung der Doppelresonanz notwendigen Komponenten wie einen steuerbaren Elektromagneten und RF-Signalquelle erweitert. Unter der Berücksichtigung der thermischen Stabilität von N@C60 wurde für zukünftige Experimente auch ein optischer Kryostat geplant, gebaut, in das Setup integriert und charakterisiert.rn Die Spin-Spin-Kopplungsexperimente wurden mit dem sauerstoffstabilen Galvinoxyl-Radikalals einem Modell-System für Kopplung durchgeführt. Dabei wurde über die Kopplung mit einem NVZentrum das RF-Spektrum des gekoppelten Radikal-Spins beobachtet. Auch konnte von dem gekoppelten Spin eine Rabi-Nutation aufgenommen werden.rn Es wurden auch weitere Aspekte der Peapod Messung und Oberflächenimplantation betrachtet.Es wurde untersucht, ob sich die NV-Detektion durch die SWCNTs, Peapods oder Fullerene stören lässt. Es zeigte sich, dass die Komponenten des geplanten Quantencomputers, bis auf die C60-Cluster, für eine ODMR-Messanordnung nicht detektierbar sind und die NV-Messung nicht stören werden. Es wurde auch betrachtet, welche Arten von kommerziellen Diamantplatten für die Oberflächenimplantation geeignet sind, für die Kopplungsmessungen geeignete Dichte der implantierten NV-Zentren abgeschätzt und eine Implantation mit abgeschätzter Dichte betrachtet.

Cadherin-11 up-regulation in overactive bladder suburothelial myofibroblasts

PURPOSE: We investigated whether the adherens junction proteins cadherin-11 and beta-catenin can be immunohistochemically visualized in the human bladder using commercially available antibodies and, if so, whether there are differences between patients with overactive bladder and refractory detrusor overactivity, and controls without lower urinary tract symptoms. MATERIALS AND METHODS: In a prospective, nonrandomized single center study 32 patients with overactive bladder and refractory detrusor overactivity, and 8 controls without lower urinary tract symptoms underwent cystoscopic bladder biopsy. Quantitative immunohistochemistry was performed. The primary outcome was cadherin-11 and beta-catenin expression in the human bladder using commercially available antibodies. The secondary outcome was differences in cadherin-11 and beta-catenin in patients with overactive bladder and refractory detrusor overactivity, and controls. RESULTS: Double labeling experiments showed co-localization of cadherin-11 and connexin 43 in the suburothelium. There was also strong co-localization of cadherin-11 and beta-catenin in the suburothelium and detrusor. Significant 2-fold up-regulation of cadherin-11 was found in the suburothelium of patients with overactive bladder compared with that in controls (p = 0.018), whereas beta-catenin was similar in the groups (p = 0.6). In the detrusor cadherin-11 and beta-catenin expression was comparable in patients with overactive bladder and controls (each p = 0.5). No difference was observed in cadherin-11 and beta-catenin in patients with overactive bladder with idiopathic vs neurogenic detrusor overactivity in the suburothelium and the detrusor (p >0.3 and >0.2, respectively). CONCLUSIONS: Using commercially available antibodies cadherin-11 and beta-catenin expression in human bladder suburothelial myofibroblasts and detrusor smooth muscle cells was noted. Cadherin-11 up-regulation in suburothelial myofibroblasts in patients with overactive bladder may be significant in overactive bladder pathogenesis.

Colocalization of a large heterodimeric proteoglycan with basement membrane proteins in cultured cells.

A novel large heterodimeric dermatan sulfate proteoglycan with core proteins of 460 and 300 kDa, respectively, had been described as a secretory product of human fetal skin fibroblasts (Breuer et al., J. Biol. Chem. 266, 13224-13232 (1991)). Pulse-chase experiments showed a preferential association of the proteoglycan with the cell membrane. Immunogold labeling indicated its localization in fibrils on the cell surface as well as in fibrillar extensions from the cell body. Immunofluorescence studies yielded a fibrillar and punctate staining pattern which was also seen in cultured human and porcine endothelial cells. Dot-like structures were observed in transformed human keratinocytes. Various immunocytochemical double-labeling experiments indicated a remarkable colocalization of the proteoglycan with fibronectin, laminin, perlecan, and type IV collagen whereas only occasionally a colocalization with chondroitin-6-sulfate was found. No evidence for an enrichment of the proteoglycan in vinculin-containing structures was obtained. These results suggest that the proteoglycan is a widely distributed macromolecule which can associate with basement membrane components. Preliminary findings in rat cornea supported this conclusion.

Resonancias de los paradigmas científicos en las arquitecturas de la Escuela de Madrid

Los años cincuenta y sesenta son los años de la incorporación definitiva de la arquitectura española al panorama internacional. Entre los arquitectos que protagonizan ese salto sin retorno, se encuentra el grupo de aquellos que unos años más tarde serán denominados por Juan Daniel Fullaondo como Escuela de Madrid. Carlos Flores, en su libro Arquitectura Española Contemporánea 1880-1950, se refiere a esos arquitectos como aquellos que se aplicaban a la difícil tarea de restablecer en España un tipo de arquitectura que conectaba con las teorías, soluciones y lenguajes establecidos por Europa durante las primeras décadas del siglo XX. Sigfried Giedion plantea en Espacio, Tiempo y Arquitectura el origen de una nueva tradición, surgida a partir de la revolución óptica de principios de siglo. Con tradición se refiere a una nueva cultura, que abarca la interrelación de las diferentes actividades del hombre: la similitud de los métodos que se usan en la arquitectura, la construcción, la pintura, el urbanismo o la ciencia. Esa novedad, fundamentada en su independencia y desvinculación con el periodo anterior, se inscribe dentro del esquema evolutivo que Thomas Kuhn plantea en su texto La Estructura de la Revoluciones Científicas, conforme a periodos no acumulativos. Kuhn habla del surgimiento de anomalías en cada periodo, origen de las crisis de pensamiento cuya explicación precisará un necesario cambio paradigmático. En la ciencia, en el campo de la óptica Thomas Young demuestra a principios del siglo XIX la naturaleza ondulatoria de la luz con su experimento de doble rendija; en el electromagnetismo se produce el salto conceptual que supone la postulación de la existencia del campo eléctrico por parte de Michael Faraday, y en termodinámica la consideración apuntada por Planck de que la radiación de la energía de produce de forma discreta, a través de cuantos. En las artes plásticas, paralelamente, Gleizes y Metzinger, en su recopilación de logros cubistas recogida en Sobre el Cubismo, hablan de la evolución sufrida durante el siglo XIX por la pintura: desde el idealismo de principios de siglo, para pasando por el realismo y la representación impresionista de la realidad, concluir prescindiendo de la perspectiva clásica. También la matemática, una vez desarrolladas por Gauss o Lobachevsky y Bolyai geometrías coherentes que incumplen el quinto postulado de Euclides, terminará dando validez a través de Riemann a los espacios ambiente en los que habitan dichas geometrías, desvinculando la relación directa entre espacio geométrico –el espacio ambiente al que da lugar un tipo de geometría- y el espacio físico. Capi Corrales refleja en su libro Contando el Espacio, cómo hasta la teoría de la relatividad y el cubismo, las geometrías no euclídeas no se hicieron notorias también fuera del campo de las matemáticas. El origen de la nueva tradición con la que Giedion se refiere a la nueva cultura de la modernidad coincide con los saltos paradigmáticos que suponen la teoría de la relatividad en las ciencias y el cubismo en las artes plásticas. Ambas se prolongan durante las primeras décadas hasta la teoría cuántica y la abstracción absoluta, barreras que los dos principales precursores de la relatividad y el cubismo, Einstein y Picasso, nunca llegan a franquear. En ese sentido Giedion habla también, además del origen, de su desarrollo, e incorpora las aportaciones periféricas en la arquitectura de Brasil, Japón o Finlandia, incluyendo por tanto la revisión orgánica propugnada por Zevi como parte de esa nueva tradición, quedando abierta a la incorporación tardía de nuevas aportaciones al desarrollo de esa cultura de la modernidad. Eliminado el concepto de la estética trascendental de Kant del tiempo como una referencia absoluta, y asumido el valor constante de la velocidad de la luz, para la teoría de la relatividad no existe una simultaneidad auténtica. Queda así fijada la velocidad de la luz como uno de los límites del universo, y la equivalencia entre masa y energía. En el cubismo la simultaneidad espacial viene motivada por la eliminación del punto de vista preferente, cuyo resultado es la multiplicidad descriptiva de la realidad, que se visualiza en la descomposición en planos, tanto del objeto como del espacio, y la consecuente continuidad entre fondo y figura que en arquitectura se refleja en la continuidad entre edificio y territorio. Sin la consideración de un punto de vista absoluto, no existe una forma auténtica. El cubismo, y su posterior desarrollo por las vanguardias plásticas, hacen uso de la geometría como mecanismo de recomposición de la figura y el espacio, adoptando mecanismos de penetración, superposición y transparencia. Gyorgy Kepes indica en El Lenguaje de la Visión que la descomposición cubista del objeto implica la sucesiva autonomía de los planos, hasta convertirse en elementos constituyentes. Algo que refleja las axonometrías arquitectónicas de Van Doesburg y que culmina con los espacios propuestos por Mies van der Rohe en sus primeros proyectos europeos. Estos mecanismos, encuentran eco en los primeros planteamientos de Javier Carvajal: en la ampliación del Panteón de españoles del cementerio de Campo Verano, un recinto virtual reconstruido mentalmente a partir del uso de tres únicos planos; o en el Pabellón de Nueva York, que organiza su planta baja desde el recorrido, introduciendo el parámetro temporal como una dimensión más. Al uso diferenciado del plano como elemento constituyente, Carvajal incorpora su plegado y su disposición conformando envolventes como mecanismo de cualificación espacial y formal, potenciando la prolongación entre arquitectura y territorio. Una continuidad que quedará culminada en las dos viviendas unifamiliares construidas en Somosaguas. La descomposición volumétrica conduce a unos niveles de abstracción que hace precisa la incorporación de elementos de la memoria -fuentes, patios, celosías…- a modo de red de señales, como las que Picasso y Braque introducen en sus cuadros para permitir su interpretación. Braque insiste en el interés por el espacio que rodea a los objetos. Una búsqueda de la tactilidad del espacio contraria a la perspectiva que aleja el objeto del observador, y que en los jardines de las viviendas de Somosaguas parece emanar de su propia materialidad. Un espacio táctil alejado del espacio geométrico y que Braque identifica con el espacio representativo en el que Poincaré, en La Ciencia y la Hipótesis, ubica nuestras sensaciones. Desdibujar los límites del objeto prolonga el espacio indefinidamente. Con el paso en el arte griego del mito al logos, se abre paso a la matemática como herramienta de comprensión de la naturaleza hasta el siglo XIX. Leon Lederman, en Simetría y la Belleza del Universo, apunta a que una de las mayores contribuciones de la teoría de Einstein es hacer cambiar el modo de pensar la naturaleza, orientándolo hacia la búsqueda de los principios de simetría que subyacen bajo las leyes físicas. Considerando que la simetría es la invariancia de un objeto o un sistema frente a una transformación y que las leyes físicas son las mismas en cualquier punto del espacio, el espacio de nuestro universo posee una simetría traslacional continua. En la ocupación del espacio de las primeras propuestas de Corrales y Molezún aparecen estructuras subyacentes que responden a enlosetados: paralelogramos sometidos a transformaciones continuas, que la naturaleza identifica tridimensionalmente con los grupos cristalográficos. Las plantas del museo de Arte Contemporáneo de la Castellana, la residencia de Miraflores, el pabellón de Bruselas o la torre Peugeot pertenecen a este grupo. La arquitectura como proceso de ocupación continua del territorio y de su trasposición al plano de cubierta, se materializa en líneas estructurales coincidentes con la estructura matemática de sus simetrías de traslación cuya posibilidad de prolongación infinita queda potenciada por el uso de la envolvente transparente. Junto a esta transparencia literal, inherente al material, Colin Rowe y Robert Slutzky nos alertan sobre otra transparencia inherente a la estructura: la transparencia fenomenal, ilustrada por los cuadros de Juan Gris, y cuya intuición aparece reflejada en la casa Huarte en Puerta de Hierro de Madrid. Corrales y Molezún insisten en una lectura de su volumetría alejada de la frontalidad, en la que los contornos de sus cubiertas inclinadas y las visuales tangenciales sugeridas por la organización de sus recorridos introducen una estructura diagonal que se superpone al entendimiento ortogonal de su planta, dibujando una intrincada red de líneas quebradas que permiten al espacio fluctuar entre las secuencia volumétrica propuesta. Los datos relativos al contenido energético de la luz y el concepto de átomo parten de la consideración de la emisión de energía en cuantos realizada por Planck, y concluyen con una circunstancia paradójica: la doble naturaleza de la luz -demostrada por la explicación de Einstein del efecto fotoeléctrico- y la doble naturaleza de la materia -asumida por Bohr y demostrada por el efecto Compton-. Schrödinger y Heisenberg formularán finalmente la ecuación universal del movimiento que rige en las ondas de materia, y cuya representación matemática es lo que se conoce como función de onda. El objeto es así identificado con su función de onda. Su ondulatoriedad expresará la probabilidad de encontrarse en un lugar determinado. Gyorgy Kepes subraya la necesidad de simplificar el lenguaje para pasar de la objetividad que aún permanece en la pintura cubista a la abstracción total del espacio. Y es así como los artistas plásticos reducen los objetos a simples formas geométricas, haciendo aflorar a la vez, las fuerzas plásticas que los tensionan o equilibran, en un proceso que acaba por eliminar cualquier atisbo de materia. Robert Rosenblum en La Pintura Moderna y la Tradición del Romanticismo Nórdico habla de cómo ese rechazo de la materia en favor de un vacío casi impalpable, campos luminosos de color denso que difunden un sereno resplandor y parecen engendrar las energías elementales de la luz natural, está directamente vinculado a la relación con la naturaleza que establece el romanticismo nórdico. La expresión de la energía de la naturaleza concentrada en un vacío que ya había sido motivo de reflexión para Michael Faraday en su postulación del concepto de campo eléctrico. Sáenz de Oíza incide en la expresión de la condición material de la energía en su propuesta junto a José Luis Romany para la capilla en el Camino de Santiago. La evocación de diferentes fuerzas electromagnéticas, las únicas junto a las gravitatorias susceptibles de ser experimentadas por el hombre, aparecerán visualizadas también en el carácter emergente de algunas de sus obras: el Santuario de Aránzazu o Torres Blancas; pero también en la naturaleza fluyente de sus contornos, la dispersión perimetral de los espacios -el umbral como centro del universoo la configuración del límite como respuesta a las tensiones germinales de la naturaleza. Miguel Fisac, a la vuelta de su viaje a los países nórdicos, aborda una simplificación lingüística orientada hacia la adecuación funcional de los espacios. En el Instituto de Daimiel, el Instituto de formación del profesorado o los complejos para los Padres Dominicos en Valladolid o Alcobendas, organiza progresivamente la arquitectura en diferentes volúmenes funcionales, incidiendo de un modo paralelo en la manifestación de los vínculos que se establecen entre dichos volúmenes como una visualización de las fuerzas que los tensionan y equilibran. En ellos la prolongación de la realidad física más allá de los límites de la envolvente ya es algo más que una simple intuición. Un proceso en el que el tratamiento de la luz como un material de construcción más, tendrá un especial protagonismo. En la iglesia de la Coronación, la iluminación del muro curvo escenifica la condición ondulatoria de la luz, manifestándose como si de un patrón de interferencia se tratara. Frente a la disolución de lo material, el espacio se manifiesta aquí como un medio denso, alejado de la tradicional noción de vacío. Una doble naturaleza, onda y partícula, que será intuido también por Fisac en la materia a través de su uso comprometido del hormigón como único material de construcción. Richard Feynmann nos alerta de la ocupación del espacio por multitud de fuerzas electromagnéticas que, al igual que la luz, precisan de receptores específicos para captar su presencia. Sus célebres diagramas suponen además la visualización definitiva de los procesos subatómicos. Al igual que la abstracción absoluta en las artes plásticas, esas representaciones diagramáticas no son asimilables a imágenes obtenidas de nuestra experiencia. Una intuición plasmada en el uso del diagrama, que irán adquiriendo progresivamente los dibujos de Alejandro de la Sota. La sección del gimnasio Maravillas recoge los trazos de sus principales elementos constructivos: estructura, cerramientos, compartimentaciones…, pero también, y con la misma intensidad, los de las fuerzas que generan su espacio, considerando así su condición de elementos constituyentes. El vacío, nos deja claro Sota, es el lugar donde habitan dichas tensiones. La posterior simplificación de las formas acompañadas de la obsesión por su aligeramiento, la casi desaparición de la envolvente, incide en aquella idea con la que Paul Klee define la actividad del artista en su Teoría del Arte Moderno, y en la que se transmite el distanciamiento hacia lo aparente: No se trata de reproducir lo visible, se trata de volver visible. Así, en Bankunión y Aviaco, como en tantos otros proyectos, frente al objetivo de la forma, Sota plantea el límite como la acotación de un ámbito de actuación. Su propia representación aséptica y diagramática transmite la renuncia a una especificidad espacial. Gilles Deleuze expresa ese posicionamiento en Pintura, el Concepto de Diagrama: el diagrama como la posibilidad de cuadros infinitos, o la posibilidad infinita de cuadros. Aparece así una concepción probabilística del espacio en la que frente a la renuncia por la forma, la tendencia al aligeramiento, y lo difuso de su definición – ideas claras, definición borrosa, en palabras de Llinás referidas al modo de operar de Sota-, la insistente atención a algunos elementos como escaleras, protecciones o miradores parece trasmitir la idea de que la arquitectura queda condensada en aquellos acontecimientos que delatan su condición dinámica, transitoria. Primando la relación frente al objeto, el vínculo frente a lo tangible. English summary. The fifties and sixties were the years of the final incorporation of Spanish architecture to the international scene. Among the architects who star that no return leap, is the group of those who a few years later will be named by Juan Daniel Fullaondo as Escuela de Madrid. Carlos Flores, in his book Arquitectura Española Contemporánea 1880-1950, refers to those architects as those that applied to the difficult task of restoring in Spain an architecture that connected with theories, solutions and established languages in Europe during the first decades of the twentieth century. Sigfried Giedion proposes in Space, Time and Architecture, the origin of a new tradition, arising from the optical revolution at the beginning of the century. With tradition he refers to a new culture, covering the interplay of different human activities: the similarity of the methods used in architecture, building, painting, urban planning or science. This new feature, based on its independence and detachment from the previous period, is part of the evolutionary scheme that Thomas Kuhn proposes in his text The Structure of Scientific Revolutions, according to non-accumulative periods. Kuhn talks about the emergence of anomalies in each period, origin of thought crisis whose explanation will require a paradigm shift needed. In science, in the field of optical Thomas Young demonstrates at the early nineteenth century the wave nature of light with its double-slit experiment , in electromagnetism the postulation of the existence of the electric field by Michael Faraday involves a conceptual leap, and in thermodynamic, the consideration pointed by Planck about quantum energy radiation. In the arts, in a parallel process, Gleizes and Metzinger , in his collection of cubism achievements on their book Du Cubisme, speak of evolution occurring during the nineteenth century by the painting: from the idealism of beginning of the century, going for realism and impressionist representation of reality, and finishing regardless of the classical perspective . Mathematics also, once developed by Gauss and Lobachevsky and Bolyai consistent geometries that violate Euclid's fifth postulate , will end validating Riemann’s ambient spaces in which these geometries inhabit, decoupling the direct relationship between geometric space -the space environment that results in a type of geometry- , and physical space. Capi Corrales reflectes in his book Contando el Espacio, that non-Euclidean geometries were not noticeable outside the field of mathematics until the theory of relativity and cubism. The origin of the new tradition that Giedion relates to the new culture of modernity coincides with paradigmatic leaps pointed by the theory of relativity in science and Cubism in the visual arts. Both are extended during the first decades until quantum theory and absolute abstraction, barriers that the two main precursors of relativity and cubism, Einstein and Picasso never overcome. In that sense Giedion speaks about the origin, but also the development, and incorporates peripheral inputs from Brazil, Japan and Finland architecture, thus including organic revision advocated by Zevi as part of this new tradition, being open to the late addition of new contributions to the development of that culture of modernity. Removed the concept of Kant's transcendental aesthetics, of time as an absolute reference, and assumed the constant value of the speed of light, theory of relativity says there is no authentic concurrency. It is thus fixed the speed of light as one of the limits of the universe, and the equivalence of mass and energy. In cubism, spatial simultaneity results from the elimination of preferential points of view, resulting in the multiplicity descriptive of reality, which is displayed in decomposition levels, both the object and the space, and the resulting continuity between figure and background that architecture is reflected in the continuity between building and land. Without the consideration of an absolute point of view, there isn’t an authentic shape. Cubism, and its subsequent development by the vanguard arts, make use of geometry as a means of rebuilding the figure and space, taking penetration mechanisms, overlapping and transparency. Gyorgy Kepes suggest in Languaje of Vision, that cubist decomposition of the object involves successive planes autonomy, to become constituent elements. Something that reflects the Van Doesburg’s architectural axonometrics and culminates with the spaces proposed by Mies van der Rohe in his first European projects. These mechanisms are reflected in the first approaches by Javier Carvajal: the extension of Spanish Pantheon in Campo Verano Cemetery, virtual enclosure mentally reconstructed from 24 the use of only three planes, or in the Spanish Pavilion of New York, which organizes its ground floor from the tour, introducing the time parameter as an additional dimension. Carvajal adds to the differential use of the plane as a constituent, Carvajal incorporates its folding and forming enclosures available as a mechanism for spatial and formal qualification, promoting the extension between architecture and territory. A continuity that will be completed in the two houses built in Somosaguas. Volumetric decomposition, as the fragmentation achieved in the last cubist experiences, needs the incorporation of elements of memory - fountains, patios, shutters...- as a network of signals, such as those introduced by Picasso and Braque in their paintings to allow their interpretation. Braque insists in his interest in the space surrounding the objects. A search of the tactility of space contrary to the perspective, which moves the observer away from the object, and that in the gardens of Somosaguas seems to emanate from its own materiality. A tactile space away from the geometric space and Braque identified with the representative space in which Poincaré in La Science et l´hypothèse, located our feelings. To blur those boundaries of the object extends the space indefinitely. With the passage in Greek art from myth to logos, it opens up to mathematics as a tool for understanding the nature until the nineteenth century. Leon Lederman, in Symmetry and beautiful Universe, suggests that one of the greatest contributions of Einstein's theory is to change the mindset of nature, namely the search for symmetry principles that underlie physical laws. Considering that symmetry is the invariance of an object or system from a transformation and that physical laws are the same at any point in space, the space of our universe has a continuous translational symmetry. In the space occupation of the first proposals by Corrales and Molezún underlying structures appear that match enlosetados: parallelograms under continuous transformations, which nature identifies tridimensionally with the crystallographic groups. Plants in the Contemporary Art Museum in La Castellana, the residence in Miraflores, the Brussels pavilion or the Peugeot tower belong to this group. The architecture as a process of continuous occupation of the territory and of its transposition to the deck, embodied in structural lines coincide with the mathematical structure of the translational symmetry and infinite extension whose possibility is enhanced by the use of the transparent cover. Alongside this literal transparency inherent to the material, Colin Rowe and Robert Slutzky alert us another transparency inherent in the structure: phenomenal transparency, illustrated by the Juan Gris’ works, and whose intuition is reflected in the Huarte’s house in Puerta de Hierro in Madrid. Corrales and Molezún insist on a reading of its volume away from the frontal, in which the outline of their inclined roofs and tangential visual suggested by the organization of his circulations introduce a diagonal structure which overlaps the orthogonal understanding of its plant, drawing an intricate web of broken lines that allow the space fluctuate between the volumetric sequence proposal. Information concerning to the energy mean of light and the concept of atom start from the consideration by Plank about the energy emission, and conclude with a paradoxical situation: the dual nature of light - demonstrated by the explanation of Einstein's photoelectric effect-, and the dual nature of matter -assumed by Bohr and demonstrated by the Compton effect-. Finally, Schrödinger and Heisenberg will formulate the universal movement equation governing in undulatory matter, whose mathematical representation is what is known as a wave function. The object is thus identified with its wave function. Its undulatory expression speaks about the probability of being found in a certain place. Gyorgy Kepes emphasizess the need to simplify the language to move from the objectivity that still remains in the cubist painting to the total abstraction of the space. And this is how artists reduced the objects to simple geometric shapes, making emerge at a time, the plastic forces that tense or balance them, in a process that eventually eliminate any trace of matter. Robert Rosenblum in Modern Painting and the Northern Romantic Tradition. Friedrich to Rothko talks about how this rejection of matter in an almost impalpable vacuum: dense color light fields that broadcast a serene glow and seem to generate the elemental energies of natural light is directly linked to the relationship with nature that sets the northern romanticism. An expression of the power of nature concentrated in a vacuum which had been reason for thought by Michael Faraday in his application of the concept of electric field. Saenz de Oíza touches upon the material expression of the energy in its proposal with Jose Luis Romany to the chapel on the Camino de Santiago. The presence of electromagnetic forces, the only ones with the gravitational one capable of being experienced by the man will also visualize in the emerging nature of some of his works: the sanctuary of Aránzazu or Torres Blancas, but also in the flowing nature of its contours, and the inclusion of interest in the realization of space fluctuating boundary: the threshold as the center of the universe. Miguel Fisac, back from his trip to the Northern Countries, starts on a linguistic simplification oriented to the functional adequacy of spaces. In the Daimiel Institute, in the Institute to Teacher Formation or in the complex to the Dominican Fathers in Valladolid or Alcobendas, progressively organized into different functional volumes architecture, focusing in a parallel way in the manifestation of the links established between these volumes as a visualization of the forces that tense and balance them. The prolongation of the physical reality beyond the limits of the envelope is already something more than a simple intuition. A process in which the treatment of light as a construction material, have a special role. In the Coronation church, curved wall lighting dramatizes the undulatory condition of the light, manifesting as if an interference pattern is involved. Versus the dissolution of the material, the space is expressed here as a dense atmosphere, away from the traditional notion of the vacuum. A dual nature, wave and particle, which is also sensed by Fisac in his committed use of concrete as a unique construction material. Richard Feynman alerts us to the occupation of space by many electromagnetic forces, which like the light, require specific receptors to capture their presence. His famous diagrams also involve the final visualization of atomic processes. As absolute abstraction in the visual arts, these representations are not assimilated to images obtained from our experience. A diagrammatic nature, abstracted from figuration, which will obtein the pictures of Alejandro de la Sota. The section of Maravillas gym collects traces of its main building blocks: structure, enclosures... but also, and with the same intensity, of the forces that generate their space as constituent elements. Sota makes it clear: the vacuum is where inhabit these tensions. The subsequent simplification of forms, accompanied by the obsession with his lightening, the near disappearance of the envelope, touches upon that idea which Paul Klee defines the activity of the artist in his Modern Art Theory, the spacing out to the apparent: it is not to reproduce the visible, it is to turn visible. Thus, in Bankunión and Aviaco, as in many other projects, against the shape, raises the limit as the dimension of a scope. His own aseptic and diagrammatic representation transmits waiver to a spatial specificity that Gilles Deleuze clearly expressed in Painting. The Concept Diagram: The diagram as the possibility of infinite pictures, or infinite possibility of the picture. Thus appears the probabilistic concept of space in which, opposite to the diffuse of its definition -clear ideas, diffuse definition, as Llinas said- the insistent attention to some elements like stairs, guards or lookouts seems to concentrate the architecture in its dynamic condition, transitional. The relationship opposite the object, the link opposite the tangible.

Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes

The possible molecular basis for the previously described antagonistic interactions between adenosine A1 receptors (A1R) and dopamine D1 receptors (D1R) in the brain have been studied in mouse fibroblast Ltk− cells cotransfected with human A1R and D1R cDNAs or with human A1R and dopamine D2 receptor (long-form) (D2R) cDNAs and in cortical neurons in culture. A1R and D1R, but not A1R and D2R, were found to coimmunoprecipitate in cotransfected fibroblasts. This selective A1R/D1R heteromerization disappeared after pretreatment with the D1R agonist, but not after combined pretreatment with D1R and A1R agonists. A high degree of A1R and D1R colocalization, demonstrated in double immunofluorescence experiments with confocal laser microscopy, was found in both cotransfected fibroblast cells and cortical neurons in culture. On the other hand, a low degree of A1R and D2R colocalization was observed in cotransfected fibroblasts. Pretreatment with the A1R agonist caused coclustering (coaggregation) of A1R and D1R, which was blocked by combined pretreatment with the D1R and A1R agonists in both fibroblast cells and in cortical neurons in culture. Combined pretreatment with D1R and A1R agonists, but not with either one alone, substantially reduced the D1R agonist-induced accumulation of cAMP. The A1R/D1R heteromerization may be one molecular basis for the demonstrated antagonistic modulation of A1R of D1R receptor signaling in the brain. The persistence of A1R/D1R heteromerization seems to be essential for the blockade of A1R agonist-induced A1R/D1R coclustering and for the desensitization of the D1R agonist-induced cAMP accumulation seen on combined pretreatment with D1R and A1R agonists, which indicates a potential role of A1R/D1R heteromers also in desensitization mechanisms and receptor trafficking.

Heteromeric association creates a P2Y-like adenosine receptor

Adenosine and its endogenous precursor ATP are main components of the purinergic system that modulates cellular and tissue functions via specific adenosine and ATP receptors (P1 and P2 receptors), respectively. Although adenosine inhibits excitability and ATP functions as an excitatory transmitter in the central nervous system, little is known about the ability of P1 and P2 receptors to form new functional structures such as a heteromer to control the complex purinergic cascade. Here we have shown that Gi/o protein-coupled A1 adenosine receptor (A1R) and Gq protein-coupled P2Y1 receptor (P2Y1R) coimmunoprecipitate in cotransfected HEK293T cells, suggesting the oligomeric association between distinct G protein-coupled P1 and P2 receptors. A1R and P2Y2 receptor, but not A1R and dopamine D2 receptor, also were found to coimmunoprecipitate in cotransfected cells. A1R agonist and antagonist binding to cell membranes were reduced by coexpression of A1R and P2Y1R, whereas a potent P2Y1R agonist adenosine 5′-O-(2-thiotriphosphate) (ADPβS) revealed a significant potency to A1R binding only in the cotransfected cell membranes. Moreover, the A1R/P2Y1R coexpressed cells showed an ADPβS-dependent reduction of forskolin-evoked cAMP accumulation that was sensitive to pertussis toxin and A1R antagonist, indicating that ADPβS binds A1R and inhibits adenylyl cyclase activity via Gi/o proteins. Also, a high degree of A1R and P2Y1R colocalization was demonstrated in cotransfected cells by double immunofluorescence experiments with confocal laser microscopy. These results suggest that oligomeric association of A1R with P2Y1R generates A1R with P2Y1R-like agonistic pharmacology and provides a molecular mechanism for an increased diversity of purine signaling.

Assembly of RecA-like recombinases: Distinct roles for mediator proteins in mitosis and meiosis

Members of the RecA family of recombinases from bacteriophage T4, Escherichia coli, yeast, and higher eukaryotes function in recombination as higher-order oligomers assembled on tracts of single-strand DNA (ssDNA). Biochemical studies have shown that assembly of recombinase involves accessory factors. These studies have identified a class of proteins, called recombination mediator proteins, that act by promoting assembly of recombinase on ssDNA tracts that are bound by ssDNA-binding protein (ssb). In the absence of mediators, ssb inhibits recombination reactions by competing with recombinase for DNA-binding sites. Here we briefly review mediated recombinase assembly and present results of new in vivo experiments. Immuno-double-staining experiments in Saccharomyces cerevisiae suggest that Rad51, the eukaryotic recombinase, can assemble at or near sites containing ssb (replication protein A, RPA) during the response to DNA damage, consistent with a need for mediator activity. Correspondingly, mediator gene mutants display defects in Rad51 assembly after DNA damage and during meiosis, although the requirements for assembly are distinct in the two cases. In meiosis, both Rad52 and Rad55/57 are required, whereas either Rad52 or Rad55/57 is sufficient to promote assembly of Rad51 in irradiated mitotic cells. Rad52 promotes normal amounts of Rad51 assembly in the absence of Rad55 at 30°C but not 20°C, accounting for the cold sensitivity of rad55 null mutants. Finally, we show that assembly of Rad51 is induced by radiation during S phase but not during G1, consistent with the role of Rad51 in repairing the spontaneous damage that occurs during DNA replication.

Close association of the alpha subunits of Gq and G11 G proteins with actin filaments in WRK1 cells: relation to G protein-mediated phospholipase C activation.

A selective polyclonal antibody directed toward the C-terminal decapeptide common to the alpha subunits of Gq and G11 G proteins (G alpha q/G alpha 11) was prepared and used to investigate the subcellular distribution fo these proteins in WRK1 cells, a rat mammary tumor cell line. In immunoblots, the antibody recognized purified G alpha q and G alpha 11 proteins and labeled only two bands corresponding to these alpha subunits. Functional studies indicated that this antibody inhibited vasopressin- and guanosine 5'-[alpha-thio]triphosphate-sensitive phospholipase C activities. Immunofluorescence experiments done with this antibody revealed a filamentous labeling corresponding to intracytoplasmic and perimembranous actin-like filament structures. Colocalization of G alpha q/G alpha 11 and F-actin filaments (F-actin) was demonstrated by double-labeling experiments with anti-G alpha q/G alpha 11 and anti-actin antibodies. Immunoblot analysis of membrane, cytoskeletal, and F-actin-rich fractions confirmed the close association of G alpha q/G alpha 11 with actin. Large amounts of G alpha q/G alpha 11 were recovered in the desmin- and tubulin-free F-actin-rich fraction obtained by a double depolymerization-repolymerization cycle. Disorganization of F-actin filaments with cytochalasin D preserved G alpha q/G alpha 11 and F-actin colocalization but partially inhibited vasopressin- and fluoroaluminate-sensitive phospholipase C activity, suggesting that actin-associated G alpha q/G alpha 11 proteins play a role in signal transduction.

Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages

Cerebral malaria (CM) is associated with high mortality and morbidity as a certain percentage of survivors suffers from persistent neurological sequelae. The mechanisms leading to death and functional impairments are yet not fully understood. This study investigated biochemical and morphological markers of apoptosis in the brains of mice infected with Plasmodium berghei ANKA. Cleaved caspase-3 was detected in the brains of animals with clinical signs of CM and immunoreactivity directly correlated with the clinical severity of the disease. Caudal parts of the brain showed more intense immunoreactivity for cleaved caspase-3. Double-labelling experiments revealed processing of caspase-3 primarily in neurons and oligodendrocytes. These cells also exhibited apoptotic-like morphological profiles in ultrastructural analysis. Further, cleavage of caspase-3 was found in endothelial cells. In contrast to neurons and oligodendrocytes, apoptosis of endothelial cells already occurred in early stages of the disease. Our results are the first to demonstrate processing of caspase-3 in different central nervous system cells of animals with CM. Apoptosis of endothelial cells may represent a critical issue for the development of the disease in the mouse model. Neurological signs and symptoms might be attributable, at least in part, to apoptotic degeneration of neurons and glia in advanced stages of murine CM.

Manual of advanced optics, by C. Riborg Mann.

Limit of resolution.--The double slit.--The Fresnel mirrors.--The Fresnel bi-prism.--The Michelson interferometer.--The visibility curves.--The prism spectrometer.--Total reflection.--The diffraction grating.--The concave grating.--Polarized light.--Rotation of the plane of polarization.--Elliptically polarized light.--The reflection of polarized light from homogeneous transparent substances.--Metallic reflection.--The spectrophotometer.--The development of optical theory.--The trend of modern optics.--Appendix.

Type 1 nitrergic (ND1) cells of the rabbit retina: Comparison with other axon-bearing amacrine cells

NADPH diaphorase (NADPHd) histochemistry labels two types of nitrergic amacrine cells in the rabbit retina. Both the large ND1 cells and the small ND2 cells stratify in the middle of the inner plexiform layer, and their overlapping processes produce a dense plexus, which makes it difficult to trace the morphology of single cells. The complete morphology of the ND1 amacrine cells has been revealed by injecting Neurobiotin into large round somata in the inner nuclear layer, which resulted in the labelling of amacrine cells whose proximal morphology and stratification matched those of the ND1 cells stained by NADPHd histochemistry. The Neurobiotin-injected ND1 cells showed strong homologous tracer coupling to surrounding ND1 cells, and double-labelling experiments confirmed that these coupled cells showed NADPHd reactivity. The ND1 amacrine cells branch in stratum 3 of the inner plexiform layer, where they produce a sparsely branched dendritic tree of 400-600 mum diameter in ventral peripheral retina. In addition, each cell gives rise to several fine beaded processes, which arise either from a side branch of the dendritic tree or from the tapering of a distal dendrite. These axon-like processes branch successively within the vicinity of the dendritic field before extending, with little or no further branching, for 3-5 mm from the soma in ventral peripheral retina. Consequently, these cells may span one-third of the visual field of each eye, and their spatial extent appears to be greater than that of most other types of axon-bearing amacrine cells injected with Neurobiotin in this study. The morphology and tracer-coupling pattern of the ND1 cells are compared with those of confirmed type 1 catecholaminergic cells, a presumptive type 2 catecholaminergic cell, the type 1 polyaxonal. cells, the long-range amacrine cells, a novel type of axon-bearing cell that also branches in stratum 3, and a type of displaced amacrine cell that may correspond to the type 2 polyaxonal cell. (C) 2004 Wiley-Liss, Inc.

Correlation of non-uniform protein expression with variation in transmitter release probability

The strength of synaptic transmission is highly variable between different synapses. The present study examined some factors that may contribute to this variation in the strength of neurotransmission in sympathetic varicosities of the mouse vas deferens. Transmitter release was measured using a focal macropatch electrode placed over pairs of visualised varicosities. By regulating the calcium concentration of the solutions inside the recording electrode and in the bath independently of each other, transmitter release was restricted to one or two surface varicosities at each recording site. Using this technique, transmitter release probability was shown to be highly variable, even between adjacent varicosities on single axon branches. Very little variation was observed in the calcium influx following single impulse nerve stimulation between adjacent Oregon Green BAPTA-1 loaded varicosities. However, the staining intensities of three vesicular proteins, SV2, synaptophysin, and synaptotagmin 1, showed considerable variation between adjacent varicosities on single axon branches. This variation in staining intensity may be partly explained by variation in the density of synaptic vesicles. However, double staining experiments using two vesicular antigens showed some varicosities staining for one vesicular antigen, but not for the second, suggesting that the expression of these release machinery proteins is regulated locally within the varicosities. The results of the present study strengthen suggestions that synaptic strength is at least in part, regulated by variation in the expression of vesicular proteins. (C) 2004 Wiley-Liss, Inc.

Visualization of enantiomers using natural abundant 13C-filtered single and double quantum selective refocusing experiments: Application to small chiral molecules

The routine use of proton NMR for the visualization of enantiomers, aligned in the chiral liquid crystal solvent poly-γ-benzyl-l-glutamate (PBLG), is restricted due to severe loss of resolution arising from large number of pair wise interaction of nuclear spins. In the present study, we have designed two experimental techniques for their visualization utilizing the natural abundance 13C edited selective refocusing of single quantum (CH-SERF) and double quantum (CH-DQSERF) coherences. The methods achieve chiral discrimination and aid in the simultaneous determination of homonuclear couplings between active and passive spins and heteronuclear couplings between the excited protons and the participating 13C spin. The CH-SERF also overcomes the problem of overlap of central transitions of the methyl selective refocusing (SERF) experiment resulting in better chiral discrimination. Theoretical description of the evolution of magnetization in both the sequences has been discussed using polarization operator formalism.

Swam Intelligent Based Inverse Model for Laboratory Double Reservoir Diffusion Experiments

Theoretical approaches are of fundamental importance to predict the potential impact of waste disposal facilities on ground water contamination. Appropriate design parameters are, in general, estimated by fitting the theoretical models to a field monitoring or laboratory experimental data. Double-reservoir diffusion (Transient Through-Diffusion) experiments are generally conducted in the laboratory to estimate the mass transport parameters of the proposed barrier material. These design parameters are estimated by manual parameter adjusting techniques (also called eye-fitting) like Pollute. In this work an automated inverse model is developed to estimate the mass transport parameters from transient through-diffusion experimental data. The proposed inverse model uses particle swarm optimization (PSO) algorithm which is based on the social behaviour of animals for finding their food sources. Finite difference numerical solution of the transient through-diffusion mathematical model is integrated with the PSO algorithm to solve the inverse problem of parameter estimation.The working principle of the new solver is demonstrated by estimating mass transport parameters from the published transient through-diffusion experimental data. The estimated values are compared with the values obtained by existing procedure. The present technique is robust and efficient. The mass transport parameters are obtained with a very good precision in less time