Mechanistic aspects of mRNA targeting for nonsense-mediated mRNA decay in human cells

The nonsense-mediated mRNA decay (NMD) pathway is best known as a translation-coupled quality control system that recognizes and degrades aberrant mRNAs with ORF-truncating premature termination codons (PTCs), but a more general role of NMD in posttranscriptional regulation of gene expression is indicated by transcriptome-wide mRNA profilings that identified a plethora of physiological mRNAs as NMD substrates. We try to decipher the mechanism of mRNA targeting to the NMD pathway in human cells. Recruitment of the conserved RNA-binding helicase UPF1 to target mRNAs has been reported to occur through interaction with release factors at terminating ribosomes, but evidence for translation-independent interaction of UPF1 with the 3’ untranslated region (UTR) of mRNAs has also been reported. We have transcriptome-wide determined the UPF1 binding sites by individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP) in human cells, untreated or after inhibiting translation. We detected a strongly enriched association of UPF1 with 3’ UTRs in undisturbed, translationally active cells. After translation inhibition, a significant increase in UPF1 binding to coding sequence (CDS) was observed, indicating that UPF1 binds RNA before translation and gets displaced from the CDS by translating ribosomes. This suggests that the decision to trigger NMD occurs after association of UPF1 with mRNA, presumably through activation of RNA-bound UPF1 by aberrant translation termination. In a second recent study, we re-visited the reported restriction of NMD in mammals to the ‘pioneer round of translation’, i.e. to cap-binding complex (CBC)-bound mRNAs. The limitation of mammalian NMD to early rounds of translation would indicate a – from an evolutionary perspective – unexpected mechanistic difference to NMD in yeast and plants, where PTC-containing mRNAs seem to be available to NMD at each round of translation. In contrast to previous reports, our comparison of decay kinetics of two NMD reporter genes in mRNA fractions bound to either CBC or the eukaryotic initiation factor 4E (eIF4E) in human cells revealed that NMD destabilizes eIF4E-bound transcripts as efficiently as those associated with CBC. These results corroborate an emerging unified model for NMD substrate recognition, according to which NMD can ensue at every aberrant translation termination event.

The biomechanics of the hip joint using new diagnostic aspects in the field of hip joint dysplasia. Constructive criticism of hip dysplasia diagnosis and present marketable breeding methods with an outlook on future perspectives and possibilities. Part I

In absence of basic canine hip biomechanics, a specific, consequent three dimensional concept to evaluate the coxofemoral joint was developed for the dog. With the help of a new method to radiologically demonstrate the hip in a physiological standing position several new clinically relevant aspects could be further investigated. For example the breed specific anatomical differences in the hip, and dynamics and the background on "iatrogenic luxations" in HD diagnostics could be shown. The caudal luxation and the growth abnormalities of the hip and their consequences on the whole leg (antetorsion syndrome) as a consequence of inadequate breeding could be demonstrated.

Teamwork reduces physiological stress in junior surgeons

Objective: The quality of teamwork depends not only on communication skills but also on team familiarity and hierarchical structures. The aim of the present study is to evaluate the physiological impact of close teamwork between senior and junior surgeons performing elective open abdominal surgery for six months in stable teams. Methods: Physiological measurements of the main and junior surgeons were taken in a total of 40 procedures. Cumulative stress was assessed by the mea- surements of urine catecholamines (Adrenaline, Noradrenaline, Dopamine, Metanephrine, Normetanephrine). Heart rate variability was measured to assess temporal aspects of stress. The procedures were observed by a trained team of work psychologists. Direct observations of distractors, team inter- actions and communication were performed. Specific questionnaires were filled by members of the surgical team that include surgeons, nurses and anesthetists. Results: In junior surgeons, physiological stress is reduced over a period of close collaboration. Case-related communication is not stressful. However, tension within the surgical team is associated with increased levels of cat- echolamine in the urine of the senior surgeon. The difficulty of the oper- ation impacts on heart-rate variability of the junior but not of the senior surgeon. Conclusion: Junior surgeons may require months of teamwork within one stable team in order to reduce levels of physiological stress. Senior surgeons are more resistant to stressful clinical situations compared to junior surgeons but are vulnerable to tension within the surgical team.

The Gut Microbiome and Cirrhosis: Basic Aspects

In this chapter the basic aspects helping to understand the microbiome in terms of quantity, diversity, complexity, function, and interaction with the host are discussed. First the nomenclature, definitions of taxa, and measures of diversity as well as methods to unravel this kingdom are outlined. A brief summary on its physiological relevance for general health and the functions exerted specifically by the microbiome is presented. Differences in the composition of the microbiome along the gastrointestinal tract and across the gut wall and its interindividual variations, enterotypes, and stability are highlighted. The reader will be familiarized with all different modulators impacting on the microbiome, namely, intrinsic and extrinsic factors. Intrinsic factors include gastrointestinal secretions (gastric acid, bile, pancreatic juice, mucus), antimicrobial peptides, motility, enteric nervous system, and host genotype. Extrinsic factors are mainly dietary choices, hygiene, stress, alcohol consumption, exercise, and medications. The second part of the chapter focuses on quantitative and qualitative changes in microbiome in liver cirrhosis. The mechanisms contributing to dysbiosis, small intestinal bacterial overgrowth, and bacterial translocation are delineated underscoring their role for the liver-gut axis.

Physiological plasticity to water flow habitat in the damselfish, Acanthochromis polyacanthus: linking phenotype to performance

The relationships among animal form, function and performance are complex, and vary across environments. Therefore, it can be difficult to identify morphological and/or physiological traits responsible for enhancing performance in a given habitat. In fishes, differences in swimming performance across water flow gradients are related to morphological variation among and within species. However, physiological traits related to performance have been less well studied. We experimentally reared juvenile damselfish, Acanthochromis polyacanthus, under different water flow regimes to test 1) whether aspects of swimming physiology and morphology show plastic responses to water flow, 2) whether trait divergence correlates with swimming performance and 3) whether flow environment relates to performance differences observed in wild fish. We found that maximum metabolic rate, aerobic scope and blood haematocrit were higher in wave-reared fish compared to fish reared in low water flow. However, pectoral fin shape, which tends to correlate with sustained swimming performance, did not differ between rearing treatments or collection sites. Maximum metabolic rate was the best overall predictor of individual swimming performance; fin shape and fish total length were 3.3 and 3.7 times less likely than maximum metabolic rate to explain differences in critical swimming speed. Performance differences induced in fish reared in different flow environments were less pronounced than in wild fish but similar in direction. Our results suggest that exposure to water motion induces plastic physiological changes which enhance swimming performance in A. polyacanthus. Thus, functional relationships between fish morphology and performance across flow habitats should also consider differences in physiology.

Spatial and temporal aspects of synaptic plasticity

The notion that changes in synaptic efficacy underlie learning and memory processes is now widely accepted even if definitive proof of the synaptic plasticity and memory hypothesis is still lacking. When learning occurs, patterns of neural activity representing the occurrence of events cause changes in the strength of synaptic connections within the brain. Reactivation of these altered connections constitutes the experience of memory for these events and for other events with which they may be associated. These statements summarize a long-standing theory of memory formation that we refer to as the synaptic plasticity and memory hypothesis. Since activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation, and is both necessary and sufficient for the information storage, we can speculate that a methodological study of the synapse will help us understand the mechanism of learning. Random events underlie a wide range of biological processes as diverse as genetic drift and molecular diffusion, regulation of gene expression and neural network function. Additionally spatial variability may be important especially in systems with nonlinear behavior. Since synapse is a complex biological system we expect that stochasticity as well as spatial gradients of different enzymes may be significant for induction of plasticity. ^ In that study we address the question "how important spatial and temporal aspects of synaptic plasticity may be". We developed methods to justify our basic assumptions and examined the main sources of variability of calcium dynamics. Among them, a physiological method to estimate the number of postsynaptic receptors as well as a hybrid algorithm for simulating postsynaptic calcium dynamics. Additionally we studied how synaptic geometry may enhance any possible spatial gradient of calcium dynamics and how that spatial variability affect plasticity curves. Finally, we explored the potential of structural synaptic plasticity to provide a metaplasticity mechanism specific for the synapse. ^

Apuntes sobre militancia, política, ocio y sociabilidad a través de la experiencia de izquierda y antifascista en el interior de la provincia de Buenos Aires en la época de la restauración conservadora (1932-1943)

El presente artículo reflexiona acerca de las relaciones existentes entre las esferas de la sociabilidad y la política desde el análisis de situaciones en que ellas confluyeron o se interpusieron en la práctica y los discursos de los dirigentes, militantes y simpatizantes izquierdistas y antifascistas en el interior de la Provincia de Buenos Aires durante los gobiernos de orientación conservadora surgidos en los años '30 y principios de los '40. Con información extraída mayoritariamente de la prensa del interior bonaerense, una fuente en general poco consultada, el texto se propone una mirada que se pose en la complejidad de las relaciones entre militancia, ocio, sociabilidad y política, que no centre únicamente en los aspectos ideológicos, la motorización y existencia de la sociabilidad política. Así, la hipótesis central que ha manejado esta investigación, es que las prácticas de sociabilidad y movilización políticas pueden analizarse en mutua correspondencia, sin remitir su construcción a una recepción unilateral y únicamente constreñida al plano ideológico y sin que su deriva se calque desde la imitación aséptica de los diseños que privilegiadamente proponen los diferentes cenáculos de la dirigencia que pretenden -fracasando necesariamente- conducir de manera total y verticalmente los múltiples fenómenos de actuación política.

Vocational and occupational counsseling: a strategy of preventive intervention directed to Young men and women from the interior of the province of Buenos Aires

This work belongs to one of the activities that are carried out in the Vocational and Occupational Guidance Center (V.O.G.C.) of the Faculty of Humanities and Educational Sciences at the L.P.N.U. In the year 1994 the Vocational/Occupational Guidance Programme for Municipalities was created, destined for work with adolescents who are attending their last year at secondary schools in the interior of the Province of Buenos Aires . The Programme aims at fostering the development of spaces for reflection related to the educational/working projects of the adolescents who are close to entering university. The proposal is based on the methodology of work groups, in the journeys preoccupations are sheared, the worries and fears experienced by the students are shared with their hosts, possibilities are used as ground for construction, dealing both with aspects of their current situation and their future possibilities. From the analysis of the group productions collected throughout these years, we have developed a student's profile that - although it resembles the one obtained from local adolescents- adds new questions and points of view, thus increasing the complexity of the balance of forces related to the question of having to make a choice.

Apuntes sobre militancia, política, ocio y sociabilidad a través de la experiencia de izquierda y antifascista en el interior de la provincia de Buenos Aires en la época de la restauración conservadora (1932-1943)

El presente artículo reflexiona acerca de las relaciones existentes entre las esferas de la sociabilidad y la política desde el análisis de situaciones en que ellas confluyeron o se interpusieron en la práctica y los discursos de los dirigentes, militantes y simpatizantes izquierdistas y antifascistas en el interior de la Provincia de Buenos Aires durante los gobiernos de orientación conservadora surgidos en los años '30 y principios de los '40. Con información extraída mayoritariamente de la prensa del interior bonaerense, una fuente en general poco consultada, el texto se propone una mirada que se pose en la complejidad de las relaciones entre militancia, ocio, sociabilidad y política, que no centre únicamente en los aspectos ideológicos, la motorización y existencia de la sociabilidad política. Así, la hipótesis central que ha manejado esta investigación, es que las prácticas de sociabilidad y movilización políticas pueden analizarse en mutua correspondencia, sin remitir su construcción a una recepción unilateral y únicamente constreñida al plano ideológico y sin que su deriva se calque desde la imitación aséptica de los diseños que privilegiadamente proponen los diferentes cenáculos de la dirigencia que pretenden -fracasando necesariamente- conducir de manera total y verticalmente los múltiples fenómenos de actuación política.

Vocational and occupational counsseling: a strategy of preventive intervention directed to Young men and women from the interior of the province of Buenos Aires

This work belongs to one of the activities that are carried out in the Vocational and Occupational Guidance Center (V.O.G.C.) of the Faculty of Humanities and Educational Sciences at the L.P.N.U. In the year 1994 the Vocational/Occupational Guidance Programme for Municipalities was created, destined for work with adolescents who are attending their last year at secondary schools in the interior of the Province of Buenos Aires . The Programme aims at fostering the development of spaces for reflection related to the educational/working projects of the adolescents who are close to entering university. The proposal is based on the methodology of work groups, in the journeys preoccupations are sheared, the worries and fears experienced by the students are shared with their hosts, possibilities are used as ground for construction, dealing both with aspects of their current situation and their future possibilities. From the analysis of the group productions collected throughout these years, we have developed a student's profile that - although it resembles the one obtained from local adolescents- adds new questions and points of view, thus increasing the complexity of the balance of forces related to the question of having to make a choice.

Apuntes sobre militancia, política, ocio y sociabilidad a través de la experiencia de izquierda y antifascista en el interior de la provincia de Buenos Aires en la época de la restauración conservadora (1932-1943)

El presente artículo reflexiona acerca de las relaciones existentes entre las esferas de la sociabilidad y la política desde el análisis de situaciones en que ellas confluyeron o se interpusieron en la práctica y los discursos de los dirigentes, militantes y simpatizantes izquierdistas y antifascistas en el interior de la Provincia de Buenos Aires durante los gobiernos de orientación conservadora surgidos en los años '30 y principios de los '40. Con información extraída mayoritariamente de la prensa del interior bonaerense, una fuente en general poco consultada, el texto se propone una mirada que se pose en la complejidad de las relaciones entre militancia, ocio, sociabilidad y política, que no centre únicamente en los aspectos ideológicos, la motorización y existencia de la sociabilidad política. Así, la hipótesis central que ha manejado esta investigación, es que las prácticas de sociabilidad y movilización políticas pueden analizarse en mutua correspondencia, sin remitir su construcción a una recepción unilateral y únicamente constreñida al plano ideológico y sin que su deriva se calque desde la imitación aséptica de los diseños que privilegiadamente proponen los diferentes cenáculos de la dirigencia que pretenden -fracasando necesariamente- conducir de manera total y verticalmente los múltiples fenómenos de actuación política.

Vocational and occupational counsseling: a strategy of preventive intervention directed to Young men and women from the interior of the province of Buenos Aires

This work belongs to one of the activities that are carried out in the Vocational and Occupational Guidance Center (V.O.G.C.) of the Faculty of Humanities and Educational Sciences at the L.P.N.U. In the year 1994 the Vocational/Occupational Guidance Programme for Municipalities was created, destined for work with adolescents who are attending their last year at secondary schools in the interior of the Province of Buenos Aires . The Programme aims at fostering the development of spaces for reflection related to the educational/working projects of the adolescents who are close to entering university. The proposal is based on the methodology of work groups, in the journeys preoccupations are sheared, the worries and fears experienced by the students are shared with their hosts, possibilities are used as ground for construction, dealing both with aspects of their current situation and their future possibilities. From the analysis of the group productions collected throughout these years, we have developed a student's profile that - although it resembles the one obtained from local adolescents- adds new questions and points of view, thus increasing the complexity of the balance of forces related to the question of having to make a choice.

Optimización de la composición del hueco de fachada en materia de eficiencia energética. Propuesta de indicador como herramienta para el análisis integral del elemento acristalado = Energy performance optimization of window systems. Proposal of an indicator as a tool for an integrated analysis of glazing

La hipótesis de esta tesis es: "La optimización de la ventana considerando simultáneamente aspectos energéticos y aspectos relativos a la calidad ambiental interior (confort higrotérmico, lumínico y acústico) es compatible, siempre que se conozcan y consideren las sinergias existentes entre ellos desde las primeras fases de diseño". En la actualidad se desconocen las implicaciones de muchas de las decisiones tomadas en torno a la ventana; para que su eficiencia en relación a todos los aspectos mencionados pueda hacerse efectiva es necesaria una herramienta que aporte más información de la actualmente disponible en el proceso de diseño, permitiendo así la optimización integral, en función de las circunstancias específicas de cada proyecto. En la fase inicial de esta investigación se realiza un primer acercamiento al tema, a través del estado del arte de la ventana; analizando la normativa existente, los componentes, las prestaciones, los elementos experimentales y la investigación. Se observa que, en ocasiones, altos requisitos de eficiencia energética pueden suponer una disminución de las prestaciones del sistema en relación con la calidad ambiental interior, por lo que surge el interés por integrar al análisis energético aspectos relativos a la calidad ambiental interior, como son las prestaciones lumínicas y acústicas y la renovación de aire. En este punto se detecta la necesidad de realizar un estudio integral que incorpore los distintos aspectos y evaluar las sinergias que se dan entre las distintas prestaciones que cumple la ventana. Además, del análisis de las soluciones innovadoras y experimentales se observa la dificultad de determinar en qué medida dichas soluciones son eficientes, ya que son soluciones complejas, no caracterizadas y que no están incorporadas en las metodologías de cálculo o en las bases de datos de los programas de simulación. Por lo tanto, se plantea una segunda necesidad, generar una metodología experimental para llevar a cabo la caracterización y el análisis de la eficiencia de sistemas innovadores. Para abordar esta doble necesidad se plantea la optimización mediante una evaluación del elemento acristalado que integre la eficiencia energética y la calidad ambiental interior, combinando la investigación teórica y la investigación experimental. En el ámbito teórico, se realizan simulaciones, cálculos y recopilación de información de distintas tipologías de hueco, en relación con cada prestación de forma independiente (acústica, iluminación, ventilación). A pesar de haber partido con un enfoque integrador, resulta difícil esa integración detectándose una carencia de herramientas disponible. En el ámbito experimental se desarrolla una metodología para la evaluación del rendimiento y de aspectos ambientales de aplicación a elementos innovadores de difícil valoración mediante la metodología teórica. Esta evaluación consiste en el análisis comparativo experimental entre el elemento innovador y un elemento estándar; para llevar a cabo este análisis se han diseñado dos espacios iguales, que denominamos módulos de experimentación, en los que se han incorporado los dos sistemas; estos espacios se han monitorizado, obteniéndose datos de consumo, temperatura, iluminancia y humedad relativa. Se ha realizado una medición durante un periodo de nueve meses y se han analizado y comparado los resultados, obteniendo así el comportamiento real del sistema. Tras el análisis teórico y el experimental, y como consecuencia de esa necesidad de integrar el conocimiento existente se propone una herramienta de evaluación integral del elemento acristalado. El desarrollo de esta herramienta se realiza en base al procedimiento de diagnóstico de calidad ambiental interior (CAI) de acuerdo con la norma UNE 171330 “Calidad ambiental en interiores”, incorporando el factor de eficiencia energética. De la primera parte del proceso, la parte teórica y el estado del arte, se obtendrán los parámetros que son determinantes y los valores de referencia de dichos parámetros. En base a los parámetros relevantes obtenidos se da forma a la herramienta, que consiste en un indicador de producto para ventanas que integra todos los factores analizados y que se desarrolla según la Norma UNE 21929 “Sostenibilidad en construcción de edificios. Indicadores de sostenibilidad”. ABSTRACT The hypothesis of this thesis is: "The optimization of windows considering energy and indoor environmental quality issues simultaneously (hydrothermal comfort, lighting comfort, and acoustic comfort) is compatible, provided that the synergies between these issues are known and considered from the early stages of design ". The implications of many of the decisions made on this item are currently unclear. So that savings can be made, an effective tool is needed to provide more information during the design process than the currently available, thus enabling optimization of the system according to the specific circumstances of each project. The initial phase deals with the study from an energy efficiency point of view, performing a qualitative and quantitative analysis of commercial, innovative and experimental windows. It is observed that sometimes, high-energy efficiency requirements may mean a reduction in the system's performance in relation to user comfort and health, that's why there is an interest in performing an integrated analysis of indoor environment aspects and energy efficiency. At this point a need for a comprehensive study incorporating the different aspects is detected, to evaluate the synergies that exist between the various benefits that meet the window. Moreover, from the analysis of experimental and innovative windows, a difficulty in establishing to what extent these solutions are efficient is observed; therefore, there is a need to generate a methodology for performing the analysis of the efficiency of the systems. Therefore, a second need arises, to generate an experimental methodology to perform characterization and analysis of the efficiency of innovative systems. To address this dual need, the optimization of windows by an integrated evaluation arises, considering energy efficiency and indoor environmental quality, combining theoretical and experimental research. In the theoretical field, simulations and calculations are performed; also information about the different aspects of indoor environment (acoustics, lighting, ventilation) is gathered independently. Despite having started with an integrative approach, this integration is difficult detecting lack available tools. In the experimental field, a methodology for evaluating energy efficiency and indoor environment quality is developed, to be implemented in innovative elements which are difficult to evaluate using a theoretical methodology This evaluation is an experimental comparative analysis between an innovative element and a standard element. To carry out this analysis, two equal spaces, called experimental cells, have been designed. These cells have been monitored, obtaining consumption, temperature, luminance and relative humidity data. Measurement has been performed during nine months and results have been analyzed and compared, obtaining results of actual system behavior. To advance this optimization, windows have been studied from the point of view of energy performance and performance in relation to user comfort and health: thermal comfort, acoustic comfort, lighting comfort and air quality; proposing the development of a methodology for an integrated analysis including energy efficiency and indoor environment quality. After theoretical and experimental analysis and as a result of the need to integrate existing knowledge, a comprehensive evaluation procedure for windows is proposed. This evaluation procedure is developed according to the UNE 171330 "Indoor Environmental Quality", also incorporating energy efficiency and cost as factors to evaluate. From the first part of the research process, outstanding parameters are chosen and reference values of these parameters are set. Finally, based on the parameters obtained, an indicator is proposed as windows product indicator. The indicator integrates all factors analyzed and is developed according to ISO 21929-1:2011"Sustainability in building construction. Sustainability indicators. Part 1: Framework for the development of indicators and a core set of indicators for buildings".

Moment transfer and influence of transverse beams in interior waffle flat plate-column connections under lateral loading

This paper addresses two aspects of the behavior of interior reinforced concrete waffle flat plate?column connections under lateral loads: the share of the unbalanced moment between flexure and excentric shear, and the effect of the transverse beams. A non-linear finite element model (benchmark model) was developed and calibrated with the results of quasi-static cyclic tests conducted on a 3/5 scale specimen. First, from this numerical model, the portion cv of the unbalanced moment transferred by the excentricity of shear about the centroid of the critical sections defined by Eurocode 2 (EC-2) and by ACI 318-11 was calculated and compared with the share-out prescribed by these codes. It is found that while the critical section of EC-2 is consistent with the cv provided by this code, in the case of ACI 318-11, the value assigned to cv is far below (about 50% smaller) the actual one obtained with the numerical simulations. Second, from the benchmark model, seven additional models were developed by varying the depth D of the transverse beam over the thickness h of the plate. It was found that the ductility of the connection and the effective width of the plate can respectively be increased up to 50% and 10% by raising D/h to 2 and 1.5.

Convento dominico de Miguel Fisac en Madrid. El acento de los objetos

La tesis estudia el Convento de Los Dominicos en Madrid (1955-1958) que representa una de las obras más importantes del arquitecto Miguel Fisac (1913-2006). Supone el punto de partida de una etapa profesional donde comienza a cualificar los espacios y a abandonar la idea de la arquitectura como volumen. El proyecto se ubica en un lugar sin apenas referencias (sólo el aire, la luz y el agua) donde Fisac incorpora objetos entendidos a distintas escalas, que acentúan la correcta organización del programa propuesto. Objetos-edificios, objetos-techos de luz y objetos táctiles pertenecen a espacios singulares del conjunto conventual que se enlazan mediante un sistema de patios como estrategia de articulación. En este edificio se encuentran las claves y conceptos que Fisac aplica posteriormente en las obras de esta etapa que acaba de comenzar. Partiendo de la hipótesis de que lo cercano cualifica el espacio, se hace hincapié en los objetos que ponen en valor los lugares más significativos y en las relaciones espaciales que se plantean entre ellos. El objetivo es analizar los recursos espaciales utilizados por Fisac en este proyecto así como la relación con el lugar, la articulación de los espacios y la preocupación por el detalle. La tesis se estructura en tres capítulos: con-texto, pre-texto y texto. El primer capítulo describe el convento, comenzando con una introducción sobre la influencia de los viajes experimentales realizados por Fisac antes del desarrollo del proyecto. Es un estudio desde el punto de vista del autor y con documentación original. El segundo capítulo analiza la obra para identificar aquellos elementos que constituyen la naturaleza del proyecto y su organización espacial enfatizando el sistema de patios como elemento estructurante y una selección de los espacios singulares de la iglesia, el refectorio y las aulas que permiten tratar temás relacionados con la planta convergente en la iglesia, la doble escala en el refectorio y la iluminación en el caso de las aulas. Estos temás se explican con la elaboración de nuevos planos que apoyan el análisis. El tercer capítulo titulado el acento de los objetos, selecciona algunos de estos elementos a distintas escalas: torre, escalera, lucernario y fuente. Con el objetivo de profundizar en cada uno de ellos se utiliza la comparativa con otras referencias que plantean temás similares para entender los conceptos planteados por Fisac y su alcance. A través de la torre y la escalera del claustro, se tratan temás relacionados con la geometría y la trama estructural. Los techos de luz plantean conceptos de iluminación, acústica y continuidad interior y los pequeños objetos de piedra, madera y metal sirven para realizar un acercamiento a la materia y a la técnica a través del detalle, que Fisac aplica en casi todas sus obras. Con la superposición de estas visiones- la del historiador, la del arquitecto y la del crítico- se calibra el grado de elaboración de la obra y se sacan las conclusiones que representan los aspectos más importantes que acomete Fisac en este proyecto. ABSTRACT This thesis studies the Convent for the Dominican Order in Madrid (1955- 1958) which represents one of the most important buildings designed by the Spanish architect Miguel Fisac(1913-2006). This work will become the first step of a professional phase where he begins to qualify the spaces and abandons the idea of Architecture as a Volume. The building is located in a site without almost any reference (only the air, the light and the water). Here, Fisac incorporates different kinds of objects understood at different scales, which emphasizes the correct organisation of the program. Object-buildings, object- ceiling light and tactile-objects belong to singular room of the Conventual complex. These items connect to each other by a system of courtyards used as a strategy for the articulation of the spaces. In this building it is possible to find the keys and concepts that Fisac will apply in following his buildings of this same period that he just has started. Based on the hypothesis that the near things qualify the space, special emphasis is put on the objects that show the great value of the most significant places and the spatial relation that is created between them. The final objective is to analyse the spatial resources used by Fisac in this project, as well as the relation created with the site, the articulation of the spaces and the emphasis on the building details. The thesis is structured around three chapters: con-text, pre-text and text. The first one describes the Seminary, starting with an introduction about the influence of the research trips did by Fisac before the project was development. It is a study from the authors point of view using original documents. The next chapter analyses his work in order to identify those elements that constitute the nature of the project and its spatial organisation with special focus on the system of courtyards as element that structure everything, and a selection of the singular spaces in the church, the refectory and the classrooms that allows to treat issues related to the church´s convergent plan, the double scale of the refectory and the lighting of the classrooms. These issues are explained by new elaborated plans that support the analyse. The third chapter titled “the emphasis on the objects” selects some of these elements in different scales: tower, stairs, skylight, and fountain. In order study in depth these elements, they are compared to other references that pose similar issues in order to understand Fisac’s concepts and scope. Through the tower and the cloister stair, he addresses certain issues in relation to the geometry and structural grid. The skylights raise lighting, acoustic and indoor continuity concepts, and the small stone, wood and metal objects are used in order to carry out an approach to the material and technique through the detail that Fisac applies in almost all his work. With the overlapping of these visions - the historian, the architect and critic - the degree of elaboration is calibrated and conclusions are met to represent the most important aspects of Fisac’s project.