The function of math5 and myocilin in mammalian eye development and disease

Complex molecular events underlie vertebrate eye development and disease. The eye is composed of two major tissue types: the anterior and posterior segments. During development, the retinal progenitor cells differentiate into six neuronal and one non-neuronal cell types. These cell types later organize into the distinct laminar structure of the mature retina which occupies the posterior segment. In the developed anterior segment, both the ciliary body and trabecular meshwork regulate intraocular pressure created by the aqueous humor. The disruption in intraocular pressure can lead to a blinding condition called glaucoma. To characterize molecular mechanisms governing retinal development and glaucoma, two separate mouse knockout lines carrying mutations in math5 and myocilin were subjected to a series of in vivo analyses. ^ Math5 is a murine homologue of Drosophila atonal , a bHLH proneural gene essential for the formation of photoreceptor cells. The expression of math5 coincides with the onset of retinal ganglion cell differentiation. The targeted deletion of mouse math5 revealed that a null mutation inhibits the formation of a majority of the retinal ganglion cells. The mutation also interferes with the normal development of other retinal cell types such as amacrine, bipolar and photoreceptor cells. These results suggest that math5 is a proneural gene responsible for differentiation of retinal ganglion cells and may also have a role in normal development of other neuronal cell types within the retina. ^ Myocilin has two unique protein coding regions bearing homology to non-muscle myosin of Dictyostelium discoideum and to olfactomedin, an extracellular matrix molecule first described in the olfactory epithelium of the bullfrog. Recently, autosomal dominant forms of myocilin mutations have been found in individuals with primary open-angle glaucoma. The genetic linkage to glaucoma suggests a role of myocilin in normal intraocular pressure and ocular function. However, the analysis of mice heterozygous and homozygous for a targeted null mutation in myocilin indicates that it is dispensable for normal intraocular pressure or ocular function. Additionally, the lack of a discernable phenotype in both heterozygous and null mice suggests that haploinsufficiency is not a critical mechanism for MYOC-associated glaucoma in humans. Instead, disease-causing mutations likely act by gain of function. ^ In summary, these studies provide novel insights into the embryonic development of the vertebrate retina, and also begin to uncover the molecular mechanisms responsible for the pathogenesis of glaucoma. ^

Integration of cooperation for development in Survey Engineering curricula at the European Higher Education Area (EHEA) framework

Survey Engineering curricula involves the integration of many formal disciplines at a high level of proficiency. The Escuela de Ingenieros en Topografía, Cartografía y Geodesia at Universidad Politécnica de Madrid (Survey Engineering) has developed an intense and deep teaching on so-called Applied Land Sciences and Technologies or Land Engineering. However, new approaches are encouraged by the European Higher Education Area (EHEA). This fact requires a review of traditional teaching and methods. Furthermore, the new globalization and international approach gives new ways to this discipline to teach and learn about how to bridge gap between cultures and regions. This work is based in two main needs. On one hand, it is based on integration of basic knowledge and disciplines involved in typical Survey Engineering within Land Management. On the other, there is an urgent need to consider territory on a social and ethical basis, as far as a part of the society, culture, idiosyncrasy or economy. The integration of appropriate knowledge of the Land Management is typically dominated by civil engineers and urban planners. It would be very possible to integrate Survey Engineering and Cooperation for Development in the framework of Land Management disciplines. Cooperation for Development is a concept that has changed since beginning of its use until now. Development projects leave an impact on society in response to their beneficiaries and are directed towards self-sustainability. Furthermore, it is the true bridge to reduce gap between societies when differences are immeasurable. The concept of development has also been changing and nowadays it is not a purely economic concept. Education, science and technology are increasingly taking a larger role in what is meant by development. Moreover, it is commonly accepted that Universities should transfer knowledge to society, and the transfer of knowledge should be open to countries most in need for developing. If the importance of the country development is given by education, science and technology, knowledge transfer would be one of the most clear of ways of Cooperation for Development. Therefore, university cooperation is one of the most powerful tools to achieve it, placing universities as agents of development. In Spain, the role of universities as agents of development and cooperation has been largely strengthened. All about this work deals to how to implement both Cooperation for Development and Land Management within Survey Engineering at the EHEA framework.

Interactive Atlas of habitability. Urban data management for the improvement of habitability and coexistence

In this paper we approximate to the understanding of the hybrid city as a context of changes, produced in the perception and in the modes of inhabiting and coexisting in cities through new technologies of information and communication.

The role of the urban support in the regeneration of vulnerable neighbourhoods

The processes of social and urban segregation have got worse during the last decades. Several studies have deepened into the analysis of the causes and consequences of these processes and have tried to define solutions that beyond eradicating some specific problems, were aimed at the consolidation of sustainable urban environments. This paper presents an approach to the problem of urban inequality based on the concept of urban vulnerability as something that goes beyond the social and economic problems. In exclusion processes it is very important to consider the urban context and the physical and structural conditions not only in each neighborhood but also in the city as a whole. The paper seeks to pose a reflection on the urban support, which is understood in all its complexity and thought to be a key to ensure access and the right to the city of the citizens most in need.

Urban sprawl and city compactness. A proposal for regional sustainability indicators. Case study of the towns of Alcorcon and Majadahonda (Comunidad de Madrid, Spain)

The main contribution of this research paper is to display a range of figures and values which could help urban planners to quantify the urban phenomenon of sprawl. In this way, after a rigorous analysis and comparison between a scattered urban fabric (Majadahonda) and a compact urban fabric (Alcorcón), several possible indexes are established and characterized in order to verify the main hypothesis: in what extent land consumption and exploitation of energy resources are higher in a scattered urban fabric than in a compact one.

Vacíos urbanos en la ciudad de Zaragoza (1975-2010). Oportunidades para la estructuración y continuidad urbana

La expansión de las ciudades hacia la periferia en las últimas décadas ha generado una serie de tejidos en colisión, donde los intersticios y los espacios residuales muestran la realidad de una ciudad dispersa. A esta serie de espacios intermedios los denominaremos “vacíos urbanos” y determinaremos una serie de factores que hagan posible su identificación Los vacíos urbanos son el objeto de la Tesis. El concepto “vacío urbano” adquiere un determinado significado para la investigación y se acota formulando una serie de parámetros para su definición. Definiremos los “vacíos urbanos” como espacios que han aparecido en el extrarradio de las ciudades, fruto de una expansión sin precedentes de las áreas urbanas. Han surgido como lugares residuales condicionados por elementos naturales o por infraestructuras, ligados a una temporalidad incierta, no inmersos en la dinámicas urbanas o habiendo perdido su funcionalidad. El objetivo de esta investigación es localizar y clasificar los vacíos existentes en la ciudad partiendo de la hipótesis de que es posible establecer una metodología para su reconocimiento y comprobación de los parámetros que los definen. La investigación centra su estudio en la ciudad de Zaragoza, como un ejemplo paradigmático, confirmando que la nueva fenomenología territorial, no sólo se manifiesta en dicha ciudad y en las áreas en concreto donde se ha estudiado, sino que más bien se trata de observarla como una serie de modelos tipológicos que respondan a un proceso de análisis. La propuesta metodológica de loa tesis pasa por reconocerlos, mostrarlos y darles una visibilidad que permita su clasificación, el desarrollo de un estudio de Áreas de la ciudad donde se localizan y un análisis de cada tipología de vacío urbano. Como instrumento metodológico se ha elaborado una detallada cartografía a diferentes escalas. La realización de los planos ha sido el medio de análisis que ha permitido localizar e interpretar los vacíos, complementado con unas escogidas fotografías de estos entornos. La metodología se convierte en un modo de descubrir y analizar los vacíos, el proceso conlleva la comprobación y la clasificación en una tipología. Según se han ido analizando nuevas áreas, se confirma como un hecho repetitivo exitoso y se observa que es aplicable a otras áreas urbanas de similares características, donde se den las condiciones principales de cada tipo. En general, deberán ser espacios localizados en la periferia de núcleos urbanos donde aparezcan fenómenos ligados a una expansión discontinua. Parece probable que el futuro de la ciudad se tenga que resolver en las próximas décadas sobre su actual extensión; bajo este supuesto, es trascendente la función que los vacíos puedan desempeñar en el futuro desarrollo urbano. Toda posibilidad de intervención precisará de una necesaria reinterpretación, puestas las miras en su potencial como elementos capaces de generar una rehabilitación urbana. A su vez se hace conveniente plantear una reflexión sobre estos espacios cargados de una dimensión social y cultural, como lugares capaces de articular y dotar de identidad al medio urbano. Los vacíos deberían protagonizar un papel relevante en la estructuración urbana, abriendo posibilidades para el tramado de la ciudad desde nuevas perspectivas. Una apuesta para que estos espacios libres pasen de ser el objetivo de procesos urbanizadores tradicionales, a ser considerados como oportunos elementos vertebradores de los entornos periurbanos, colaborando en el objetivo de una ciudad contemporánea sostenible. ABSTRACT In the last decades the city periphary expansion has provoked a series of matters to collide, where interstices and waste lands show the reality of a divided city. We shall determine a number of factors allowing us to treat these “in between” spaces, also called "urban voids" as identifiable elements. We will consider them the subject of the thesis and establish them as a "concept", delimiting the meaning of the research specifically acquired, defining, and formulating a set of parameters. "Urban voids" are defined as spaces that have appeared on the outskirts of cities, the result of an unprecedented expansion of urban areas. They have emerged as waste lands, conditioned by natural elements or infrastructure, related to uncertain temporality, not immersed in the urban dynamics, or having lost their functionality. It seems likely that in the upcoming decades, the future of the city will have to resolve its current way of expanding . It is under this assumption that urban voids, as intermediate spaces, will play an important role in future urban developments. Any possible intervention will require a necessary reinterpretation, closely watching their potential as elements capable of generating an urban rehabilitation. At the same time, we wish to reflect on these spaces, in many cases loaded with a social and cultural dimension, as places able to articulate and give identity to the urban environment. Based on the hypothesis that it is possible to establish a methodology for recognition and verification, the purpose of this research is to locate and classify the existing urban voids in the city. The research focuses its study on the city of Saragossa which can be seen as a paradigmatic example. The objective is to confirm that this new territorial phenomenology, not only manifests itself in Saragossa and specific areas under study, but also, can be observed as a series of typological models that respond to a review process. The methodological proposal will recognize, demonstrate, and exhibit these urban voids, in a light that will allow us to classify them, examine the different areas where they can be found, and develop a tipology analysis of each type of urban void found. The technical tool used in this research is a detailed mapping at different scales. A realization of plans, as a mean of analysis, supplemented with a few selected pictures of these environments, will facilitate the location and interpretation of these voids. This scholarly approach to discover and analyze urban voids will involve checking and classifying them in a typology. It has been confirmed as a successful constant regulator while exploring new areas. It will be apply to other urban areas with similar characteristics, that is, spaces located on the periphery of urban areas where expansion is linked to the appearence of discontinuous phenomena. The urban voids play a fundamental role within the urban structure, providing the city a weaving scheme with opportunities of fresh perspectives. The challenge for these free spaces is to move from being the consequence of traditional urban development processes, to being considered opportune backbone elements of peri-urban environments, and to finally contribute to the objectives of a sustainable contemporary city.

Los programas de regularización urbana en Brasil y su adecuación a los nuevos paradigmas urbanos tras el "Estatuto da Cidade": un estudio de casos en la ciudad de Porto Alegre, Rio Grande do Sul

En América Latina, y en Brasil en particular, las ocupaciones informales de la tierra urbana se tornaran un fenómeno generalizado en todas las ciudades, hecho que evidencio una serie de problemas urbanos y de ineficiencia en el proveimiento de los derechos básicos de los ciudadanos, principalmente el derecho a la morada digna, con eso, trajo la necesidad de priorización de política publicas curativas, como los programas de regularización urbana, cuyo objetivo es la inserción de las ocupaciones informales en la ciudad formal, con todos los impactos que eso genera: urbanísticos, legales, sociales y económicos. La ley federal intitulado Estatuto da Cidade (EC), reglamentada en 2001, es entendida como un avanzo jurídico por justamente intentar contrabalancear ese contexto, trayendo una serie de principios e instrumentos que buscan garantizar la función social de la propiedad y de la ciudad. Esa nueva lógica, en la teoría, tiene que ser la base de todas las políticas urbanas del país. Con eso, esa tesis tiene como objetivo evaluar si, realmente, los programas de regularización urbana desarrollados en Brasil cumplen con los dictámenes de dicha legislación. Para eso, fue elegido la metodología del estudio de caso, que fue desarrollado en la ciudad de Porto Alegre, capital del Rio Grande do Sul. Primero fue analizado el Estatuto da Cidade, para la definición de los principios de evaluación, luego, fue propuesto un sistema de evaluación, que fue aplicado en los dos casos estudiados: un anterior a la promulgación del EC, el Condominio dos Anjos, que serbio como parámetro referencial, y otro desarrollado tras la promulgación de dicha legislación, el Programa Integrado Entrada da Cidade (PIEC). Tras los análisis, se puede concluir que la legislación federal efectivamente no ha tenido el reflejo necesario, como conclusiones principales se puede citar: que la legislación municipal de Porto Alegre desde la década 90 ya tenía avances considerables, incluso algunos sirvieron de ejemplo en la elaboración del EC, luego, eso puede explicar el bajo impacto percibido; y que el principal fiscalizador y delineador de la política urbana es el financiador del programa, luego, muchas estrategias y dibujos proyectuales dependen de la línea de dicha financiación. ABSTRACT In Latin America, and Brazil in particular, informal urban land occupations pervasive be turned into all cities, a fact evidenced a series of urban problems and inefficiency to provide the basic rights of citizens, mainly the right to a decent housing, with that, brought the need for prioritization of public policy, such as urban regularization programs, aimed at the inclusion of informal occupations in the formal city, with all the impacts that generates: urban, legal, social and economic. Federal law entitled Estatuto da Cidade (EC), regulated in 2001, is understood as a legal advanced for just try to counterbalance this context, bringing a number of principles and instruments that seek to guarantee the social function of property and the city. This new logic, in theory, has to be the basis of all urban policies of the country. With that, this thesis aims to assess whether urban regularization programs developed in Brazil, actually, comply with the dictates of that legislation. For that, it was elected the methodology of the case study, which was developed in the city of Porto Alegre, capital of Rio Grande do Sul, Brazil. It was first analyzed the EC, for defining the principles for evaluation, then, was proposed an evaluation system, which was applied in two case studies: one before the promulgation of the EC, the Condominio dos Anjos, which used as a reference parameter, and another developed following the enactment of this legislation, the Program Integrate Entrada da Cidade (PIEC). After the analysis, it can be concluded that the federal legislation has not actually had the reflection necessary, main conclusions can be cited: the municipal legislation in Porto Alegre, since the early 90s, had considerable progress, including some served as an example in developing the EC, then, that may explain the low perceived impact; the principal auditor and eyeliner urban policy is the founder of the program, of course, many strategies and project drawings depend on the line of financing.

De la desintegración Espacial a la Conformación regional en la Sabana de Bogotá. Una Propuesta para el desarrollo de la Ciudad Región en el siglo XXI

El presente trabajo de investigación aborda el tema del desarrollo regional en torno a una gran metrópoli como Bogotá y la Sabana de Bogotá. El crecimiento, expansión y relación con los municipios vecinos. Su entorno territorial; es un tema de discusión que cada día adquiere más fuerza desde hace varias décadas. Bogotá y la Sabana de Bogotá, se consideran en la actualidad como un caso representativo del caótico modelo de expansión urbana y crecimiento demográfico, enfrentado al desarrollo urbano como paradigma de la desigualdad de la ciudad latinoamericana. Son muchos los procesos y conflictos de naturaleza Regional y metropolitana que atraviesa la capital colombiana. Sin embargo esta investigación abordada el tema desde la necesidad de gobernanza y coordinación para el desarrollo territorial consensuado y equilibrado de la Región. La sabana de Bogotá está conformada por ciudades dormitorio, ciudades industriales, turísticas, agropecuarias, etc., es atravesada por el Río Bogotá, y en su centro la gran metrópoli, Bogotá D.C. centro de trabajo muy importante a nivel nacional, su área de influencia más próxima llega hasta: Caqueza, Zipaquira, Facatativa, Soacha, Fusagasuga y Girardot. Principales polos de desarrollo en la sabana y el departamento. Cundinamarca está compuesto por 15 provincias y Bogotá. Conformando un sistema de redes urbanas con necesidades comunes y demanda servicios públicos, de transporte, aseo, movilidad, salud, educación, espacio público y calidad ambiental. La metodología de esta investigación consiste en el análisis de la región a partir de la articulación de planes de ordenamiento territorial en un área de estudio propuesta. Mediante entrevistas con profesionales, expertos, funcionarios y empleados públicos y teniendo en cuenta las posibilidades legales en Colombia para el desarrollo territorial regional, establecer la situación real en materia de desarrollo para el departamento de Cundinamarca, evidenciando las necesidades del territorio y su desarrollo de una forma más compleja, valorando las sinergias y necesidades sociales, ambientales y económicas propias del crecimiento urbano, para proponer una serie de directrices que estructuren un desarrollo regional equilibrado en Bogotá y Cundinamarca. El análisis de los modelos del caso contribuye a fortalecer iniciativas para el desarrollo Regional de la Sabana de Bogotá como territorio sostenible: ambiental, económico y socialmente. En un sistema de redes que interconecte a Bogotá, con Cundinamarca, Colombia y el resto del mundo. Cundinamarca como región debe fijar estrategias y articular políticas en función de un modelo de desarrollo urbano regional para el departamento y la Sabana de Bogotá. Directrices departamentales básicas y fundamentales para el desarrollo territorial equilibrado que promueva ciudades sostenibles, compactas y con Calidad de vida para todos sus habitantes. ABSTRACT: This research addresses the issue of regional development around a big metropolis like Bogotá and Sabana de Bogota. The growth, expansion and relations with neighboring municipalities. Your local environment; It is an issue that becomes stronger every day for decades. Bogotá and Sabana de Bogotá, are considered today as a representative case of the chaotic model of urban expansion and population growth, urban development faced as a paradigm of inequality in Latin American city. Many processes and conflicts of Regional and metropolitan nature that crosses the Colombian capital. However this research addressed the issue from the need for governance and coordination for consensual and balanced territorial development of the region. The savannah of Bogota consists of bedroom communities, industrial cities, tourism, agriculture, etc., is crossed by the Bogota River, and at its center the great metropolis, Bogota DC center very important work at the national level, the area closest influence reaches: Caqueza, Zipaquira, Facatativa, Soacha, Fusagasuga and Girardot. Main centers of development in the savannah and the department. Cundinamarca is composed of 15 provinces and Bogota. Forming a system of urban networks with common needs and demand utilities, transportation, grooming, mobility, health, education, public space and environmental quality. The methodology of this research is the analysis of the region from the joint land use plans in the proposed study area. Through interviews with professionals, experts, public officials and employees and taking into account the legal possibilities in Colombia for regional territorial development, establish the real situation in development for the department of Cundinamarca, showing the region's needs and development of a more complex form, assessing synergies and own social, environmental and economic needs of urban growth, to propose a set of guidelines to structure a balanced regional development in Bogota and Cundinamarca. The analysis of case models helps to strengthen initiatives for regional development of the Sabana de Bogota and sustainable region: environmentally, economically and socially. In a network system that interconnects to Bogotá with Cundinamarca, Colombia and elsewhere. Cundinamarca region should set as joint strategies and policies based on a model of regional urban development for the department and the Sabana de Bogota. Basic and fundamental to balanced territorial development that fosters sustainable, compact and quality of life for all its inhabitants cities departmental guidelines.

Mies van der Rohe's Illinois Institute of Technology: Analysis and History of a Compositive Development = El IIT de Mies van der Rohe: análisis e historia de un proceso compositivo

The Illinois Institute of Technology (iit) campus, Chicago, by architect Ludwig Mies van der Rohe, is often considered as a transitional work, usually acknowledged as significant for the reorientation of his professional career after he emigrated to the United States. Moreover, its favorable recognition today is somehow indicative of its relevance as a model for urban intervention in the contemporary American city and for contemporary city planning in general, not to mention the profound impact that it had on the cityscape of Chicago. However, today we know it was rather the result of a close collaboration between he and Ludwig Hilberseimer —later on, to be completed with Alfred Caldwell— who merged their personal ideas and expertise in the design for the first time. In addition to this, when one tries to locate the design within its own historical context and evaluate the sources of its approach to it, some contradictions arise. The major impact of the images produced by Mies to promote its realization —widely disseminated in most contemporary architectural periodicals— probably outshined the particular circumstances in which the design was conceived. In fact, it would never be materialized as originally presented, but it was, instead, continuously reworked according to land availability in the site —a circumstance often ignored by subsequent architectural critic, that enthusiastically praised the design even before it was fully completed. One of the main consequences of looking at iit from such a standpoint is that, when historically contextualized, one can appreciate that, due to the urban scale of its implementation process, the design had to face a complex reality very different to that initially planned by the architect, often far from his actual possibilities of intervention. Such approach is in contradiction with the common description of the design as a ‘tabula rasa’ that allegedly would have been formulated on the basis of a full denial of its context. On the contrary, the ever-changing circumstances of the design motivated a necessary re-interpretation of the relation between its executed fragments, in order to keep the original identity of the whole in an ever-changing context. This situation implied a continuous transformation of the design by means of a steady re-composition of its elements: as the number of completed buildings increased in its successive stages, their relation to their site-specific context changed, in a very particular process that these lines try to delineate. Requiring decades to be erected, neither of its authors would ever see the design finished as planned, partially because of the difficulties in acquiring the extension of land that it required. Considering the study of this process as able to provide a valuable gateway to understand the urban discourse that the architects entailed, the aim of these lines is to analyze the problems that the iit campus design had to face. As a starting point, a relationship between practice and theory in the activity of the authors implied in iit campus design has been assumed. Far from being interrupted during World War ii, strong historical evidence can be found to infer that both were developed in parallel. Consequently, the historical sequence of the preserved testimonies has been put into context, as well as their transformation while Mies remained in charge for the campus Master Plan. Notably, when seen from this perspective, some ideas already expressed during his previous European practice were still present during the design process. Particularly, Mies's particular understanding of certain architectural concepts — such as those of ‘order’ and ‘structure’—can be traced paralleling the theories about urban planning from his collaborators, a fact that possibly facilitated the campus successful development. The study of the way these ideas were actually redeveloped and modified in the American urban context, added to the specific process of the implementation of iit campus design, sheds a new light for a critical interpretation of the reasons that made it possible, and of the actual responsibility of Mies's collaborators in its overall development and final completion. RESUMEN El campus del Illinois Institute of Technology (iit) de Chicago, obra del arquitecto Ludwig Mies van der Rohe, es a menudo considerado como una obra de transición que, por lo general, ha venido siendo reconocida como relevante para la reorientación de su carrera profesional posterior a su exilio en los Estados Unidos. El reconocimiento del que goza el proyecto es indicativo, de algún modo, de su importancia como modelo para la intervención urbana en la ciudad norteamericana contemporánea y el planeamiento de la ciudad contemporánea en general, sin olvidar el profundo impacto que ha tenido sobre el paisaje urbano de Chicago. Sin embargo, hoy sabemos que el resultado se benefició de su estrecha colaboración con Ludwig Hilberseimer y se completaría más tarde con la de Alfred Caldwell, quienes unieron sus ideas y experiencia profesional en el proyecto por primera vez. Asimismo, cuando se intenta ubicar el proyecto dentro de su propio contexto histórico y evaluar los criterios de su manera de abordarlo, surgen algunas contradicciones. El considerable impacto de las imágenes producidas por Mies para impulsar su ejecución —ampliamente difundidas en la mayoría de publicaciones de arquitectura de la época— probablemente eclipsó las particulares circunstancias en las que el proyecto fue concebido. De hecho, nunca llegó a materializarse tal y como fue inicialmente presentado. Por contra, fue reelaborado de manera continua, de acuerdo a la disponibilidad de suelo en el emplazamiento; una circunstancia a menudo ignorada por la crítica posterior, que elogió con entusiasmo el proyecto antes siquiera de que fuese terminado. Una de las principales consecuencias de contemplar el iit desde semejante punto de vista es que, una vez contextualizada históricamente su puesta en obra, se puede apreciar que el arquitecto tuvo que enfrentarse a una compleja realidad urbana muy diferente a la inicialmente prevista —probablemente debido a la escala del proyecto— a menudo lejos de sus posibilidades reales de intervención. Este enfoque contradice la descripción habitual del proyecto como una ‘tabula rasa’, que supuestamente se habría formulado sobre la base de una negación completa de su contexto. Por el contrario, las circunstancias cambiantes del proyecto obligaron una necesaria reinterpretación de la relación entre sus frag mentos ejecutados, con el fin de mantener la identidad original del conjunto en un contexto en constante cambio. Esta situación implicó una continua transformación del proyecto por medio de una permanente re-composición de sus elementos: según se incrementaba el número de edificios construidos en las etapas sucesivas de desarrollo del conjunto, variaba su relación con el contexto específico en que se emplazaban, en un proceso muy particular que estas líneas tratan de perfilar. Al necesitar décadas para ser levantado, ninguno de sus autores vería el conjunto terminado según lo planificado, en parte debido a las dificultades para la adquisición de la extensión de suelo que demandaba. Asumiendo que el estudio de este proceso es capaz de proporcionar una valiosa puerta de entrada para elucidar el discurso urbano asumido por los Mies, el objetivo de estas líneas es analizar los problemas a los que el proyecto del campus del iit tuvo que enfrentarse. Como punto de partida, se ha supuesto una relación entre la práctica y la teoría en la actividad de los autores implicados en el proyecto del campus del iit. Lejos de interrumpirse durante la Segunda Guerra Mundial, existen evidencias históricas sólidas para deducir que ambas vertientes se desarrollaron en paralelo. En consecuencia, se ha contextualizado la secuencia histórica de los testimonios conservados, así como su transformación durante el periodo en que Mies estuvo a cargo del Plan General del campus. Significativamente, al ser contempladas bajo esta perspectiva, algunas ideas ya expresadas durante su práctica europea anterior resultan aún presentes durante la redacción del proyecto. En concreto, se puede trazar un paralelismo entre la comprensión particular de Mies de ciertos conceptos arquitectónicos —como los de ‘orden’ y ‘estructura’— y las teorías sobre el urbanismo de sus colaboradores, hecho que posiblemente facilitó el exitoso desarrollo del proyecto. El estudio de la manera en que estas ideas fueron reelaboradas y modificadas en el contexto urbano estadounidense, sumado al proceso específico de su aplicación en el proyecto del campus del iit, arroja una nueva luz para una interpretación crítica tanto de las razones que lo hicieron posible, como del papel real que los colaboradores de Mies tuvieron en su desarrollo y ejecución final.

Loss of function of the tuberous sclerosis 2 tumor suppressor gene results in embryonic lethality characterized by disrupted neuroepithelial growth and development

Germline defects in the tuberous sclerosis 2 (TSC2) tumor suppressor gene predispose humans and rats to benign and malignant lesions in a variety of tissues. The brain is among the most profoundly affected organs in tuberous sclerosis (TSC) patients and is the site of development of the cortical tubers for which the hereditary syndrome is named. A spontaneous germline inactivation of the Tsc2 locus has been described in an animal model, the Eker rat. We report that the homozygous state of this mutation (Tsc2Ek/Ek) was lethal in mid-gestation (the equivalent of mouse E9.5–E13.5), when Tsc2 mRNA was highly expressed in embryonic neuroepithelium. During this period homozygous mutant Eker embryos lacking functional Tsc2 gene product, tuberin, displayed dysraphia and papillary overgrowth of the neuroepithelium, indicating that loss of tuberin disrupted the normal development of this tissue. Interestingly, there was significant intraspecies variability in the penetrance of cranial abnormalities in mutant embryos: the Long–Evans strain Tsc2Ek/Ek embryos displayed these defects whereas the Fisher 344 homozygous mutant embryos had normal-appearing neuroepithelium. Taken together, our data indicate that the Tsc2 gene participates in normal brain development and suggest the inactivation of this gene may have similar functional consequences in both mature and embryonic brain.

Cloning of a Tobacco Apoplasmic Invertase Inhibitor1 : Proof of Function of the Recombinant Protein and Expression Analysis during Plant Development

Higher plants express several isoforms of vacuolar and cell wall invertases (CWI), some of which are inactivated by inhibitory proteins at certain stages of plant development. We have purified an apoplasmic inhibitor (INH) of tobacco (Nicotiana tabacum) CWI to homogeneity. Based on sequences from tryptic fragments, we have isolated a full-length INH-encoding cDNA clone (Nt-inh1) via a reverse transcriptase-polymerase chain reaction. Southern-blot analysis revealed that INH is encoded by a single- or low-copy gene. Comparison with expressed sequence tag clones from Arabidopsis thaliana and Citrus unshiu indicated the presence of Nt-inh1-related proteins in other plants. The recombinant Nt-inh1-encoded protein inhibits CWI from tobacco and Chenopodium rubrum suspension-cultured cells and vacuolar invertase from tomato (Lycopersicon esculentum) fruit, whereas yeast invertase is not affected. However, only in the homologous system is the inhibition modulated by the concentration of Suc as previously shown for INH isolated from tobacco cells. Highly specific binding of INH to CWI could be shown by affinity chromatography of a total cell wall protein fraction on immobilized recombinant Nt-inh1 protein. RNA-blot analysis of relative transcript ratios for Nt-inh1 and CWI in different parts of adult tobacco plants revealed that the expression of both proteins is not always coordinate.

Function of the pre-T-cell receptor alpha chain in T-cell development and allelic exclusion at the T-cell receptor beta locus.

The pre-T-cell receptor, composed of the T-cell receptor (TCR) beta chain (TCRbeta), pre-Talpha (pTalpha) chain, and CD3 molecules, has been postulated to be a transducer of signals during the early stages of T-cell development. To examine the function of the transmembrane pTalpha chain during tbymocyte development, we generated pTalpha-/- embryonic stem cells and assayed their ability to differentiate into lymphoid cells in vivo after injection into recombination-activating gene (RAG)-2-deficient blastocysts. Thymocytes representing all stages of T-cell differentiation were detected in the thymus of pTalpha-/- chimeric mice, indicating that thymocyte development can occur without pTalpha. However, greatly reduced thymocyte numbers and substantially increased percentages of both CD4-CD8- thymocytes and TCRgammadelta+ thymocytes suggest that pTalpha plays a critical role in thymocyte expansion. To investigate the role of the pTalpha chain in allelic exclusion at the TCRbeta locus, a functionally rearranged TCRbeta minigene was introduced into pTalpha-/- and pTalpha+/- embryonic stem cells, which were subsequently assayed by RAG-2-deficient blastocyst complementation. In the absence of pTalpha, expression of the transgenic TCRbeta inhibited rearrangement of the endogenous TCRbeta locus to an extent similar to that seen in normal TCRbeta transgenic mice, suggesting that pTalpha may not be required for signaling allelic exclusion at the TCRbeta locus.

Normal development and function of natural killer cells in CD3 epsilon delta 5/delta 5 mutant mice.

The CD3 epsilon polypeptide contributes to the cell surface display as well as to the signal transduction properties of the T-cell antigen receptor complex. Intriguingly, the distribution of CD3 epsilon is not restricted to T cells, since activated mouse, human, and avian natural killer (NK) cells do express intracytoplasmic CD3 epsilon polypeptides. CD3 epsilon is also present in the cytoplasm of fetal thymic T/NK bipotential progenitor cells, suggesting that it constitutes a component of the NK differentiation program. We report here that the genetic disruption of CD3 epsilon exon 5 alters neither NK cell development nor in vitro and in vivo NK functions, although it profoundly blocked T-cell development. These results support the notion that CD3 epsilon is dispensable for mouse NK cell ontogeny and function and further suggest that the common NK/T-cell progenitor cell utilizes CD3 epsilon as a mandatory component only when differentiating toward the T-cell lineage.