Conformational analysis of a potent SSTR3-selective somatostatin analogue by NMR in water solution

The three-dimensional structure of a potent SSTR3-selective analogue of somatostatin, cyclo(3-14)H-Cys(3)-Phe(6)-Tyr(7)-D-Agl(8)(N(beta) Me, 2-naphthoyl)-Lys(9)-Thr(10)-Phe(11)-Cys(14)-OH (des-AA(1, 2, 4, 5, 12, 13)[Tyr(7), D-Agl(8)(N(beta) Me, 2-naphthoyl)]-SRIF) (peptide 1) has been determined by (1)H NMR in water and molecular dynamics (MD) simulations. The peptide exists in two conformational isomers differing mainly by the cis/trans isomerization of the side chain in residue 8. The structure of 1 is compared with the consensus structural motifs of other somatostatin analogues that bind predominantly to SSTR1, SSTR2/SSTR5 and SSTR4 receptors, and to the 3D structure of a non-selective SRIF analogue, cyclo(3-14)H-Cys(3)-Phe(6)-Tyr(7)-D-2Nal(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)-OH (des-AA(1, 2, 4, 5, 12, 13)[Tyr(7), D-2Nal(8)]-SRIF) (peptide 2). The structural determinant factors that could explain selectivity of peptide 1 for SSTR3 receptors are discussed.

Structural conservations and diversities of dsRNA viruses: Structural studies of the cytoplasmic polyhedrosis virus by electron cryomicroscopy and 3D reconstruction

The Reoviridae virus family is a group of economically and pathologically important viruses that have either single-, double-, or triple-shelled protein layers enclosing a segmented double stranded RNA genome. Each virus particle in this family has its own viral RNA dependent RNA polymerase and the enzymatic activities necessary for the mature RNA synthesis. Based on the structure of the inner most cores of the viruses, the Reoviridae viruses can be divided into two major groups. One group of viruses has a smooth surfaced inner core, surrounded by complete outer shells of one or two protein layers. The other group has an inner core decorated with turrets on the five-fold vertices, and could either completely lack or have incomplete outer protein layers. The structural difference is one of the determinant factors for their biological differences during the infection. ^ Cytoplasmic polyhedrosis virus (CPV) is a single-shelled, turreted virus and the structurally simplest member in Reoviridae. It causes specific chronic infections in the insect gut epithelial cells. Due to its wide range of insect hosts, CPV has been engineered as a potential insecticide for use in fruit and vegetable farming. Its unique structural simplicity, unparalleled capsid stability and ease of purification make CPV an ideal model system for studying the structural basis of dsRNA virus assembly at the highest possible resolution by electron cryomicroscopy (cryoEM) and three-dimensional (3D) reconstruction. ^ In this thesis work, I determined the first 3D structure of CPV capsids using 100 kV cryoEM. At an effective resolution of 17 Å, the full capsid reveals a 600-Å diameter, T = 1 icosahedral shell decorated with A and B spikes at the 5-fold vertices. The internal space of the empty CPV is unoccupied except for 12 mushroom-shaped densities that are attributed to the transcriptional enzyme complexes. The inside of the full capsid is packed with icosahedrally-ordered viral genomic RNA. The interactions of viral RNA with the transcriptional enzyme complexes and other capsid proteins suggest a mechanism for RNA transcription and subsequent release. ^ Second, the interactions between the turret proteins (TPs) and the major capsid shell protein (CSPs) have been identified through 3D structural comparisons of the intact CPV capsids with the spikeless CPV capsids, which were generated by chemical treatments. The differential effects of these chemical treatment experiments also indicated that CPV has a significantly stronger structural integrity than other dsRNA viruses, such as the orthoreovirus subcores, which are normally enclosed within outer protein shells. ^ Finally, we have reconstructed the intact CPV to an unprecendented 8 Å resolution from several thousand of 400kV cryoEM images. The 8 Å structure reveals interactions among the 120 molecules of each of the capsid shell protein (CSP), the large protrusion protein (LPP), and 60 molecules of the turret protein (TP). A total of 1980 α-helices and 720 β-sheets have been identified in these capsid proteins. The CSP structure is largely conserved, with the majority of the secondary structures homologous to those observed in the x-ray structures of corresponding proteins of other reoviruses, such as orthoreovirus and bluetongue virus. The three domains of TP are well positioned to play multifunctional roles during viral transcription. The completely non-equivalent interactions between LPP and CSP and those between the anchoring domain of TP and CSP account for the unparalleled stability of this structurally simplest member of the Reoviridae. ^

Calidad de vida : apertura y perspectiva filosófica

Este trabajo está orientado como apertura a la reflexión sobre un tema con implicancias en el campo de las Ciencias de la Salud, en general, y en el de la Odontología, específicamente. El concepto calidad de vida se refiere a la relación entre las capacidades a nivel biológico, psicológico y social que se alcanzan en el individuo. Nuestro aporte sigue los lineamientos de la concepción integral del ser humano, en donde la salud hace referencia a la dinámica vital contextualizada en una cultura, una época, un sistema de creencias y valores y condicionantes socio-económicos Desde la filosofía presentamos un enfoque reflexivo sobre las bases conceptuales de “calidad de vida", con la finalidad de favorecer el vínculo interdisciplinario entre la Odontología y las Ciencias Humanas.

La luz natural como generadora del espacio arquitectónico de la catedral gótica

La historia de la construcción de las catedrales góticas es la historia de la búsqueda de la luz. Esta afirmación casi metafísica, recoge una realidad asumida por todos los historiadores tanto de la arquitectura antigua como del resto de las artes. La luz en el gótico ha sido descrita bajo múltiples matices como son su carácter simbólico, cromático e incluso místico, sin embargo no existe, en el estudio del conocimiento de la luz gótica, ninguna referencia a la misma como realidad física cuantificable, cualificable y por tanto, clasificable. La presente tesis doctoral aborda el concepto de la iluminación gótica desde una perspectiva nueva. Demuestra, con un método analítico inédito, que la iluminación gótica es cuantificable y cualificable. Para ello analiza en profundidad la iluminación de una selección de 6 edificios muestra, las catedrales de Gerona, Toledo, Sevilla y León, la basílica de Santa María del Mar y la capilla de la Sainte Chapelle de París, mediante una toma de datos “in situ” de iluminación y su comparación con los datos lumínicos obtenidos por un programa de soleamiento de la simulación en tres dimensiones de los distintos proyectos originales góticos. El análisis exhaustivo de las muestras y su introducción en el método analítico descrito, permite determinar, en primer lugar, unas cualidades inéditas que identifican la luz de los espacios góticos según unos parámetros nuevos como son la intensidad, expresividad, recorrido, distorsión y color. También describe cuales son los factores determinantes, de nuevo inéditos, que modulan cada una de las cualidades y en que proporción lo hacen cada uno de ellos. Una vez establecidas las cualidades y los factores que las definen, la tesis doctoral establece los rangos en los que se mueven las distintas cualidades y que conformarán la definitiva clasificación según “tipos de cualidad lumínica”. Adicionalmente, la tesis propone un procedimiento abreviado de acercamiento a la realidad de la iluminación gótica a través de unas fórmulas matemáticas que relacionan los factores geométricos detectados y descritos en la tesis con el resultado luminoso del espacio en lo que concierne a las dos cualidades más importantes de las reflejadas, la intensidad y la expresividad. Gracias a este método y su procedimiento abreviado, la clasificación se hace extensible al resto de catedrales góticas del panorama español y europeo y abre el camino a nuevas clasificaciones de edificios históricos de distintas épocas, iniciando un apasionante camino por recorrer en la recuperación de “la luz original”. Esta clasificación y sus cualidades podrán a su vez, ser utilizadas como herramientas de conocimiento de un factor determinante a la hora de describir cualquier espacio gótico y su aportación pretende ser un nuevo condicionante a tener en cuenta en el futuro, ayudando a entender y respetar, en las posibles intervenciones a realizar sobre el patrimonio arquitectónico, aquello que fue en su inicio motor principal del proyecto arquitectónico y que hoy día no se valora suficientemente tan solo por falta de conocimiento: su luz. The history of the construction of the Gothic cathedrals is the history of the search for light. This almost etaphysical statement reflects a reality accepted by all historians both of ancient architecture and other arts. Light in the Gothic period has been described under multiple approaches such as its symbolic, chromatic and even mystical character. However, in the study of the Gothic light, no references exist to it as a physical quantifiable and qualifiable reality and therefore, classifiable. This dissertation deals with the concept of Gothic light from a new perspective. With a new analytical method, it shows that Gothic lighting is quantifiable and can be classified regarding quality. To this end, a selection of 6 buildings light samples are analyzed; the cathedrals of Gerona, Toledo, Seville and León, the basilica of Santa María of the Sea and the Sainte Chapelle in Paris. "In situ" lighting data is collected and it is compared with lighting data obtained by a program of sunlight of the 3D simulation of various Gothic original projects. The comprehensive analysis of the samples and the data introduced in the analytical method described, allows determining, first, important qualities that identify the light of Gothic spaces according to new parameters such as intensity, expressiveness, trajectory, distortion and color. It also describes the determinant factors, which modulate each of the qualities and in what proportion they do it. Once the qualities and factors that define them have been established, in this doctoral dissertation the ranges regarding different qualities are set, which will make up the final classification according to "types of light quality". In addition, this work proposes an abbreviated procedure approach to the reality of the Gothic lighting through some mathematical formulae, relating the geometric factors identified and described in the study with the bright result of space regarding the two most important qualities of the light,intensity and expressiveness. Thanks to this method and to the abbreviated procedure, the classification can be applied to other Spanish and European Gothic cathedrals and opens up the way to new classifications of historic buildings from different eras, starting an exciting road ahead in the recovery of the "original light". This classification and its qualities may in turn be used as tools to know a determinant factor when describing any Gothic space. Its contribution is intended to be a new conditioning factor to keep in mind in the future, helping to understand and respect, in possible interventions on the architectural heritage, what was the main engine to start the architectural project and which today is not valued enough due to the lack knowledge: the light.

Thermal, stress, and traps effects in AlGaN/GaN HEMTs

GaN y AlN son materiales semiconductores piezoeléctricos del grupo III-V. La heterounión AlGaN/GaN presenta una elevada carga de polarización tanto piezoeléctrica como espontánea en la intercara, lo que genera en su cercanía un 2DEG de grandes concentración y movilidad. Este 2DEG produce una muy alta potencia de salida, que a su vez genera una elevada temperatura de red. Las tensiones de puerta y drenador provocan un stress piezoeléctrico inverso, que puede afectar a la carga de polarización piezoeléctrica y así influir la densidad 2DEG y las características de salida. Por tanto, la física del dispositivo es relevante para todos sus aspectos eléctricos, térmicos y mecánicos. En esta tesis se utiliza el software comercial COMSOL, basado en el método de elementos finitos (FEM), para simular el comportamiento integral electro-térmico, electro-mecánico y electro-térmico-mecánico de los HEMTs de GaN. Las partes de acoplamiento incluyen el modelo de deriva y difusión para el transporte electrónico, la conducción térmica y el efecto piezoeléctrico. Mediante simulaciones y algunas caracterizaciones experimentales de los dispositivos, hemos analizado los efectos térmicos, de deformación y de trampas. Se ha estudiado el impacto de la geometría del dispositivo en su auto-calentamiento mediante simulaciones electro-térmicas y algunas caracterizaciones eléctricas. Entre los resultados más sobresalientes, encontramos que para la misma potencia de salida la distancia entre los contactos de puerta y drenador influye en generación de calor en el canal, y así en su temperatura. El diamante posee une elevada conductividad térmica. Integrando el diamante en el dispositivo se puede dispersar el calor producido y así reducir el auto-calentamiento, al respecto de lo cual se han realizado diversas simulaciones electro-térmicas. Si la integración del diamante es en la parte superior del transistor, los factores determinantes para la capacidad disipadora son el espesor de la capa de diamante, su conductividad térmica y su distancia a la fuente de calor. Este procedimiento de disipación superior también puede reducir el impacto de la barrera térmica de intercara entre la capa adaptadora (buffer) y el substrato. La muy reducida conductividad eléctrica del diamante permite que pueda contactar directamente el metal de puerta (muy cercano a la fuente de calor), lo que resulta muy conveniente para reducir el auto-calentamiento del dispositivo con polarización pulsada. Por otra parte se simuló el dispositivo con diamante depositado en surcos atacados sobre el sustrato como caminos de disipación de calor (disipador posterior). Aquí aparece una competencia de factores que influyen en la capacidad de disipación, a saber, el surco atacado contribuye a aumentar la temperatura del dispositivo debido al pequeño tamaño del disipador, mientras que el diamante disminuiría esa temperatura gracias a su elevada conductividad térmica. Por tanto, se precisan capas de diamante relativamente gruesas para reducer ele efecto de auto-calentamiento. Se comparó la simulación de la deformación local en el borde de la puerta del lado cercano al drenador con estructuras de puerta estándar y con field plate, que podrían ser muy relevantes respecto a fallos mecánicos del dispositivo. Otras simulaciones se enfocaron al efecto de la deformación intrínseca de la capa de diamante en el comportamiento eléctrico del dispositivo. Se han comparado los resultados de las simulaciones de la deformación y las características eléctricas de salida con datos experimentales obtenidos por espectroscopía micro-Raman y medidas eléctricas, respectivamente. Los resultados muestran el stress intrínseco en la capa producido por la distribución no uniforme del 2DEG en el canal y la región de acceso. Además de aumentar la potencia de salida del dispositivo, la deformación intrínseca en la capa de diamante podría mejorar la fiabilidad del dispositivo modulando la deformación local en el borde de la puerta del lado del drenador. Finalmente, también se han simulado en este trabajo los efectos de trampas localizados en la superficie, el buffer y la barrera. Las medidas pulsadas muestran que tanto las puertas largas como las grandes separaciones entre los contactos de puerta y drenador aumentan el cociente entre la corriente pulsada frente a la corriente continua (lag ratio), es decir, disminuir el colapse de corriente (current collapse). Este efecto ha sido explicado mediante las simulaciones de los efectos de trampa de superficie. Por su parte, las referidas a trampas en el buffer se enfocaron en los efectos de atrapamiento dinámico, y su impacto en el auto-calentamiento del dispositivo. Se presenta también un modelo que describe el atrapamiento y liberación de trampas en la barrera: mientras que el atrapamiento se debe a un túnel directo del electrón desde el metal de puerta, el desatrapamiento consiste en la emisión del electrón en la banda de conducción mediante túnel asistido por fonones. El modelo también simula la corriente de puerta, debida a la emisión electrónica dependiente de la temperatura y el campo eléctrico. Además, también se ilustra la corriente de drenador dependiente de la temperatura y el campo eléctrico. ABSTRACT GaN and AlN are group III-V piezoelectric semiconductor materials. The AlGaN/GaN heterojunction presents large piezoelectric and spontaneous polarization charge at the interface, leading to high 2DEG density close to the interface. A high power output would be obtained due to the high 2DEG density and mobility, which leads to elevated lattice temperature. The gate and drain biases induce converse piezoelectric stress that can influence the piezoelectric polarization charge and further influence the 2DEG density and output characteristics. Therefore, the device physics is relevant to all the electrical, thermal, and mechanical aspects. In this dissertation, by using the commercial finite-element-method (FEM) software COMSOL, we achieved the GaN HEMTs simulation with electro-thermal, electro-mechanical, and electro-thermo-mechanical full coupling. The coupling parts include the drift-diffusion model for the electron transport, the thermal conduction, and the piezoelectric effect. By simulations and some experimental characterizations, we have studied the device thermal, stress, and traps effects described in the following. The device geometry impact on the self-heating was studied by electro-thermal simulations and electrical characterizations. Among the obtained interesting results, we found that, for same power output, the distance between the gate and drain contact can influence distribution of the heat generation in the channel and thus influence the channel temperature. Diamond possesses high thermal conductivity. Integrated diamond with the device can spread the generated heat and thus potentially reduce the device self-heating effect. Electro-thermal simulations on this topic were performed. For the diamond integration on top of the device (top-side heat spreading), the determinant factors for the heat spreading ability are the diamond thickness, its thermal conductivity, and its distance to the heat source. The top-side heat spreading can also reduce the impact of thermal boundary resistance between the buffer and the substrate on the device thermal behavior. The very low electrical conductivity of diamond allows that it can directly contact the gate metal (which is very close to the heat source), being quite convenient to reduce the self-heating for the device under pulsed bias. Also, the diamond coated in vias etched in the substrate as heat spreading path (back-side heat spreading) was simulated. A competing mechanism influences the heat spreading ability, i.e., the etched vias would increase the device temperature due to the reduced heat sink while the coated diamond would decrease the device temperature due to its higher thermal conductivity. Therefore, relative thick coated diamond is needed in order to reduce the self-heating effect. The simulated local stress at the gate edge of the drain side for the device with standard and field plate gate structure were compared, which would be relevant to the device mechanical failure. Other stress simulations focused on the intrinsic stress in the diamond capping layer impact on the device electrical behaviors. The simulated stress and electrical output characteristics were compared to experimental data obtained by micro-Raman spectroscopy and electrical characterization, respectively. Results showed that the intrinsic stress in the capping layer caused the non-uniform distribution of 2DEG in the channel and the access region. Besides the enhancement of the device power output, intrinsic stress in the capping layer can potentially improve the device reliability by modulating the local stress at the gate edge of the drain side. Finally, the surface, buffer, and barrier traps effects were simulated in this work. Pulsed measurements showed that long gates and distances between gate and drain contact can increase the gate lag ratio (decrease the current collapse). This was explained by simulations on the surface traps effect. The simulations on buffer traps effects focused on illustrating the dynamic trapping/detrapping in the buffer and the self-heating impact on the device transient drain current. A model was presented to describe the trapping and detrapping in the barrier. The trapping was the electron direct tunneling from the gate metal while the detrapping was the electron emission into the conduction band described by phonon-assisted tunneling. The reverse gate current was simulated based on this model, whose mechanism can be attributed to the temperature and electric field dependent electron emission in the barrier. Furthermore, the mechanism of the device bias via the self-heating and electric field impact on the electron emission and the transient drain current were also illustrated.

Análisis de la durabilidad de la cubierta plana invertida, a través del estudio de las interacciones e incompatibilidades entre las membranas sintéticas y el poliestireno extrusionado

La cubierta plana invertida se forma, cuando sobre una membrana impermeable se coloca un aislamiento térmico. Estos materiales pueden separarse con capas auxiliares que impiden el contacto directo entre ellos. Muchos de los materiales que forman esta solución constructiva pueden ser polímeros, como lo son algunas membranas impermeables, las capas auxiliares separadoras o el poliestireno extrusionado (XPS). La mayoría de los polímeros son incompatibles entre sí, por lo que en esta tesis se plantea como hipótesis la posibilidad de que se produzcan interacciones e incompatibilidades entre algunos de estos materiales. Por ello se hace una búsqueda bibliográfica y documental de otras investigaciones que pudieran estar relacionadas con el tema, y se estudian y analizan normas y documentación facilitada por fabricantes. Sin embargo, tras consultar toda la bibliografía y documentación que se referencia en esta tesis doctoral, no fue encontrado ningún trabajo de investigación sobre la influencia de la interacción entre los materiales que componen las cubiertas planas invertidas, y de cómo afecta esta a la durabilidad de las mismas. El propósito de esta tesis es el análisis de la durabilidad de la cubierta plana invertida, desde el punto de vista de las interacciones e incompatibilidades que pueden producirse entre los materiales formantes de esta solución constructiva. Además de este objetivo general, se estudian alternativas que puedan prolongar el ciclo de vida de la cubierta plana invertida. Para ello, se desarrolla un plan experimental con el fin de analizar dichas incompatibilidades, y estudiar los factores que las condicionan. Algunos de los resultados obtenidos, muestran que determinadas láminas impermeables utilizadas normalmente para la construcción de cubiertas planas, pueden interactuar con el XPS y sufrir deterioro. El contacto con el mismo, la incorrecta separación, la presión y el calor, son factores determinantes para que se produzca deterioro. Se puede señalar como una de las conclusiones de esta investigación, que la protección térmica que proporciona el XPS a la cubierta plana invertida, puede no ser suficiente (dependiendo del espesor del mismo, y de la ubicación de la cubierta fundamentalmente), para reducir la cantidad de calor que alcanza la línea de contacto entre los materiales, y por tanto paliar las interacciones que se producen. Además, aunque los geotextiles utilizados como capas auxiliares separadoras, en los gramajes por metro cuadrado, recomendados por algunas de las normas reguladoras de este tipo de cubiertas minoran las interacciones, estas siguen produciéndose. ABSTRACT The inverted flat roof is formed from a waterproofing membrane on which the thermal insulation is placed. These materials may be separated with auxiliary layers, which prevent the direct contact between them. Many of the materials forming this constructive solution can be polymers, such as some waterproofing membranes, the auxiliary separating layers, or the extruded polystyrene board (XPS). Most polymers are incompatible, so this thesis hypothesized that interactions and incompatibilities between some of these materials might be possible. Therefore, a literature search, and other documentation that could be related to the topic, are studied and analyzed, as well as, standards and documentation provided by manufacturers. However, after consulting all literature and documents referenced in this dissertation, it was not found any research about the influence of interaction between the materials forming the inverted flat roof, and how this affects to the durability of them. The purpose of this thesis is the analysis of the durability of the inverted flat roof, from the point of view of interactions and incompatibilities may occur between the materials setting up this constructive solution. Along with this general objective, alternatives that can prolong the life cycle of the inverted roof are studied. To get this, an experimental plan is developed, in order to analyze these incompatibilities, and study the factors conditioning them. Some of the results show, that certain normally used waterproofing laminas for building flat roofs, may interact with XPS producing lamina deterioration. Contact, incorrect separation, pressure and heat, are determinant factors for degradation. It can be pointed out, as one of the conclusions of this research, that the thermal protection provided by XPS to the inverted flat roof, cannot be enough (depending on the XPS thickness, and the location of the flat mainly) to reduce the amount of heat that reaches the contact line between materials, and thus to cut down interactions. Furthermore, although geotextiles used as auxiliary separating layers, within the weights per square meter recommended by some of the regulating rules of this type of roofs reduce interactions, these still occur.

Habitar al borde del agua : villas del siglo XX

Las casas del siglo XX construidas al borde del mar –escenario único y origen de su expresión- siguen la topografía del suelo que habitan en su descenso al agua, y organizan espacios que obtienen miradas al horizonte marino. El horizonte nos confronta a lo desconocido. La vista del mar incita al deseo de recorrerlo, al deseo de viajar. Con origen en el otium romano, la presencia del agua define un modo de vida apacible –epicúreo- que los viajeros de la arquitectura -que nos acompañan en la tesis- traducen en sus refugios más íntimos. Experimentan con los cambios en los conceptos y en las técnicas, que se trasladan fácilmente a la arquitectura de la casa al borde del agua desde los inicios del Movimiento Moderno. Sus espacios del habitar frente al mar nos permiten descubrir estrategias comunes en sus respuestas más modernas. El arquitecto ante el proyecto frente al mar llega a la ubicación elegida, mira hacia el horizonte, y desplazándose ladera arriba se coloca en un punto estratégico que elige; después, delante de su tablero, recorre el camino inverso, coloca el lugar y sobre él dibuja los elementos que configurarán los espacios de la casa buscando esa mirada al mar. Las situaciones y ubicaciones posibles son infinitas; se definen algunas consonancias espaciales comunes en los suelos que se ocupan debidas a la presencia del mar que asociamos entre sí. De la comparación entre todas las casas -emblemas del XX-, surgen múltiples variantes de la mirada y de espacios al abierto, y modos de fabricar entornos con criterios comunes para dominar la visión del mar. Interiores que se abren al panorama, espacios cuyas ventanas buscan su mirada en la extensión del horizonte, rescisiones y aperturas. Reconocemos condicionantes en el territorio a los que las villas responden, categorías arquitectónicas que dan respuesta frente al mar en la búsqueda del moderno, la topografía, la mirada y el espacio al abierto. Las casas comparten la idea del dominio del paisaje desde el punto más alto, y en algunos suelos se invierte la tipología por la topografía, confirmando así un criterio común basado en la lectura del suelo como consecuencia de la búsqueda del espacio de la mirada. Los espacios al abierto se significan en todas ellas, son espacios al -aire libre- abiertos, unos envueltos, otros porticados, puertas del horizonte que se abren al exterior, en el techo de la casa, otros cubiertos y abiertos, espacios entre interior y exterior, en plataformas con bancales o patios envolventes, recintos o habitaciones abiertas. Descubrimos un logro del XX en los espacios positivos o negativos que traducen o juegan con el entorno, que ocupan o sustraen de los contornos construidos y que obtienen espacios intermedios en la búsqueda de la relación con el mar. Las herramientas que se utilizan son los dibujos de los autores, de las casas visitadas, el elenco de viajeros y sus viajes, el conocimiento desde el estudio de los proyectos. A través de la comparación por aproximaciones parciales, los dibujos nos definen la mirada al mar, el modo de ocupación y la forma de relación con el paisaje. La arquitectura del habitar frente al mar en el XX, hecha para y por arquitectos, topografía el suelo y construye la mirada, fabricando espacios al abierto en la relación entre la casa y el entorno marítimo. ABSTRACT Houses of the 20th century built by the sea – a unique setting which gives rise to their expression – follow the topography of the land they occupy in its descent towards the sea, and they organize spaces which give views of the maritime horizon. The horizon brings us face to face with the unknown. The sea view provokes a desire to cross it, to travel. The presence of the sea defines a peaceful, epicurean way of life, with origins in the Roman otium, which architectural travellers – who accompany us through the thesis – translate into their most intimate retreats. They experiment with changes in concepts and techniques, which are easily transferred to the architecture of the seaside house since the beginnings of the Modern Movement. Their living spaces allow us to discover common strategies in the most modern responses. The architect with a seaside project arrives at the site, looks towards the horizon, then walks uphill and chooses a strategic point; then with his drawing board he retraces his steps, he sets the position and then draws in the elements that make up the house that seeks a sea view. The number of potential situations and locations is infinite; certain common spatial accordances are defined in land which is occupied due to the presence of the sea. Comparison of all the houses – 20th century emblems – throws up multiple variations of view and open spaces, and ways of creating settings with common criteria so as to command the vision of the sea. Interiors which open up to the panorama, spaces whose windows seek their view in the expanse of the horizon, openings and closures. We recognise determinant factors in the territory to which the villas respond, architectural categories which give a seaside solution to the search for the modern, the topography, the view, and the open space. The houses share the idea of dominating the landscape from the highest point, and in some areas typology and topography are inverted, thus confirming a common criteria based on the reading of the ground as a conse quence of the search for the view space. Open spaces stand out in all the villas – spaces open to the outdoor air - some are wrapped, some arcaded, doors to the horizon which open up to the exterior, on the roof of the house. There are open and covered spaces, spaces between the exterior and interior, on platforms with banks and surrounding patios, enclosures and open rooms. We discover an achievement of the 20th century in the positive and negative spaces which translate and play with the setting, which occupy or are extracted from built contours and which obtain intermediate spaces in the search for the relationship with the sea. The tools used are the author’s drawings of the houses visited, the cast of travelling companions and their travels, the knowledge gained from study of the projects. Through comparison by means of partial approaches, the drawings define the view of the sea, the occupation mode and the way of relating to the landscape. Architecture for living by the sea in the 20th century, carried out both by and for the architects, shapes the land and constructs the view, creating open spaces in the relationship between the house and the sea surroundings.

Stochastic choice analysis of tourism destinations

The analysis of tourist destination choice, defined by intra-country administrative units and by product types “coastal/inland and village/city”, permits the characterisation of tourist flow behaviour, which is fundamental for public planning and business management. In this study, we analyse the determinant factors of tourist destination choice, proposing various research hypotheses relative to the impact of destination attributes and the personal characteristics of tourists. The methodology applied estimates Nested and Random Coefficients Multinomial Logit Models, which allow control over possible correlations among different destinations. The empirical application is realised in Spain on a sample of 3,781 individuals and allows us to conclude that prices, distance to the destination and personal motivations are determinants in destination choice.

Analysing three basic decisions of tourists: going away, going abroad and going on tour

This study analyses determinant factors in the taking of three basic decisions on the part of holidaymakers: going on holiday, foreign holidays and multi-destination holidays. We propose various research hypotheses relating to the impact on these decisions of various personal characteristics. The methodology used estimates various Binomial Logit models. The empirical application carried out in Spain on a sample of 3,781 individuals allows us to conclude that personal characteristics related to the chosen destination, personal restrictions and socio-demographic and psychographic characteristics are determinants of these decisions.

Evaluación de las comunicaciones de un congreso de marketing y su posterior publicación

Tradicionalmente, la literatura ha evidenciado debilidades en el sistema de revisión por pares en el ámbito de los artículos publicados en revistas. Hasta la fecha apenas se ha dedicado atención a estas debilidades en el campo de los congresos. Este trabajo examina los factores determinantes de las evaluaciones por pares que reciben las comunicaciones de los congresos a partir de las características de sus autores y del propio manuscrito. Asimismo, analiza la relación existente entre el grado de aceptación/rechazo de las comunicaciones y la calidad de las publicaciones posteriores que se derivan de las mismas. Los resultados obtenidos en un congreso de marketing evidencian que la orientación cuantitativa, las referencias bibliográficas y las notas a pie de página influyen en la evaluación por pares de las comunicaciones. Además, se detecta que aquellas comunicaciones que son aceptadas para su presentación en el congreso, posteriormente resultan publicadas en revistas de mayor calidad.

A função respiratória dos doentes adultos com fibrose quística, em repouso e no esforço

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

Knowledge acquisition in international strategic alliances among Malaysian manufacturing firms

This thesis examines the process of knowledge acquisition by Malaysian manufacturing firms through their involvement in international strategic alliances. The strategic alliances can be with or without equity involvement. Firms involved with a foreign partner with equity involvement are joint venture firms while non-equity involvement are firms that engaged in contractual agreements. Using empirical evidence from 65 international alliances gathered through a survey conducted in high-technology manufacturing sectors, several factors that influence the process of knowledge acquisition are examined. The factors are: learning capacity, experience, goals, active involvement and accessibility to the foreign knowledge. Censored regression analysis and ordered probit analysis are used to analyse the effects of these factors on knowledge acquisition and its determinant parts, and the effects of knowledge acquisition and its determinants on the performance of the alliances. A second questionnaire gathered evidence relating to the factors, which encouraged tacit knowledge transfer between the foreign and Malaysian partners in international alliances. The key findings of the study are: knowledge acquisition in international strategic alliances is influenced by five determining factors; learning capacity, experience, articulated goals, active involvement and accessibility; new technology knowledge, product development knowledge and manufacturing process knowledge are influenced differently by the determining factors; knowledge acquisition and its determinant factors have a significant impact on the firm’s performance; cultural differences tend to moderate the effect on the firm’s performance; acquiring tacit knowledge is not only influenced by the five determinant factors but also by other factors, such as dependency, accessibility, trust, manufacturing control, learning methods and organisational systems; Malaysian firms involved in joint ventures tend to acquire more knowledge than those involved in contractual agreements, but joint ventures also exhibit higher degrees of dependency than contractual agreements; and the presence of R&D activity in the Malaysian partner encourages knowledge acquisition, but the amount of R&D expenditure has no effect on knowledge acquisition.

Tangibilidade, classe de ativos e estrutura de capital das empresas listadas na BM&FBOVESPA

This study aims to investigate the influence of the asset class and the breakdown of tangibility as determinant factors of the capital structure of companies listed on the BM & FBOVESPA in the period of 2008-2012. Two current assets classes were composed and once they were grouped by liquidity, they were also analyzed by the financial institutions for credit granting: current resources (Cash, Bank and Financial Applications) and operations with duplicates (Stocks and Receivables). The breakdown of the tangible assets was made based on its main components provided as warrantees for loans like Machinery & Equipment and Land & Buildings. For an analysis extension, three metrics for leverage (accounting, financial and market) were applied and the sample was divided into economic sectors, adopted by BM&FBOVESPA. The data model in dynamic panel estimated by a systemic GMM of two levels was used in this study due its strength to problems of endogenous relationship as well as the omitted variables bias. The found results suggest that current resources are determinants of the capital structure possibly because they re characterized as proxies for financial solvency, being its relationship with debt positive. The sectorial analysis confirmed the results for current resources. The tangibility of assets has inverse proportional relationship with the leverage. As it is disintegrated in its main components, the significant and negative influence of machinery & equipment was more marked in the Industrial Goods sector. This result shows that, on average, the most specific assets from operating activities of a company compete for a less use of third party resources. As complementary results, it was observed that the leverage has persistence, which is linked with the static trade-off theory. Specifically for financial leverage, it was observed that the persistence is relevant when it is controlled for the lagged current assets classes variables. The proxy variable for growth opportunities, measured by the Market -to -Book, has the sign of its contradictory coefficient. The company size has a positive relationship with debt, in favor of static trade-off theory. Profitability is the most consistent variable in all the performed estimations, showing strong negative and significant relationship with leverage, as the pecking order theory predicts

Tangibilidade, classe de ativos e estrutura de capital das empresas listadas na BM&FBOVESPA

This study aims to investigate the influence of the asset class and the breakdown of tangibility as determinant factors of the capital structure of companies listed on the BM & FBOVESPA in the period of 2008-2012. Two current assets classes were composed and once they were grouped by liquidity, they were also analyzed by the financial institutions for credit granting: current resources (Cash, Bank and Financial Applications) and operations with duplicates (Stocks and Receivables). The breakdown of the tangible assets was made based on its main components provided as warrantees for loans like Machinery & Equipment and Land & Buildings. For an analysis extension, three metrics for leverage (accounting, financial and market) were applied and the sample was divided into economic sectors, adopted by BM&FBOVESPA. The data model in dynamic panel estimated by a systemic GMM of two levels was used in this study due its strength to problems of endogenous relationship as well as the omitted variables bias. The found results suggest that current resources are determinants of the capital structure possibly because they re characterized as proxies for financial solvency, being its relationship with debt positive. The sectorial analysis confirmed the results for current resources. The tangibility of assets has inverse proportional relationship with the leverage. As it is disintegrated in its main components, the significant and negative influence of machinery & equipment was more marked in the Industrial Goods sector. This result shows that, on average, the most specific assets from operating activities of a company compete for a less use of third party resources. As complementary results, it was observed that the leverage has persistence, which is linked with the static trade-off theory. Specifically for financial leverage, it was observed that the persistence is relevant when it is controlled for the lagged current assets classes variables. The proxy variable for growth opportunities, measured by the Market -to -Book, has the sign of its contradictory coefficient. The company size has a positive relationship with debt, in favor of static trade-off theory. Profitability is the most consistent variable in all the performed estimations, showing strong negative and significant relationship with leverage, as the pecking order theory predicts