Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial.

BACKGROUND A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa. METHODS For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system. After laboratory confirmation of a new case, clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to immediate vaccination or delayed (21 days later) vaccination with rVSV-ZEBOV (one dose of 2 × 10(7) plaque-forming units, administered intramuscularly in the deltoid muscle). Adults (age ≥18 years) who were not pregnant or breastfeeding were eligible for vaccination. Block randomisation was used, with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 vs >20 individuals). The study is open label and masking of participants and field teams to the time of vaccination is not possible, but Ebola response teams and laboratory workers were unaware of allocation to immediate or delayed vaccination. Taking into account the incubation period of the virus of about 10 days, the prespecified primary outcome was laboratory-confirmed Ebola virus disease with onset of symptoms at least 10 days after randomisation. The primary analysis was per protocol and compared the incidence of Ebola virus disease in eligible and vaccinated individuals in immediate vaccination clusters with the incidence in eligible individuals in delayed vaccination clusters. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. FINDINGS Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV. In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7-100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination. At the cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI -7·1 to 94·2; p=0·1791), and 76·3% (95% CI -15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing. INTERPRETATION The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy. FUNDING WHO, with support from the Wellcome Trust (UK); Médecins Sans Frontières; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre, and Department of Foreign Affairs, Trade and Development.

The contributions of the hippocampal formation, perirhinal cortex and areas TH/TF to object, spatial and contextual recognition memory in primates

Adult monkeys (Macaca mulatta) with lesions of the hippocampal formation, perirhinal cortex, areas TH/TF, as well as controls were tested on tasks of object, spatial and contextual recognition memory. ^ Using a visual paired-comparison (VPC) task, all experimental groups showed a lack of object recognition relative to controls, although this impairment emerged at 10 sec with perirhinal lesions, 30 sec with areas TH/TF lesions and 60 sec with hippocampal lesions. In contrast, only perirhinal lesions impaired performance on delayed nonmatching-to-sample (DNMS), another task of object recognition memory. All groups were tested on DNMS with distraction (dDNMS) to examine whether the use of active cognitive strategies during the delay period could enable good performance on DNMS in spite of impaired recognition memory (revealed by the VPC task). Distractors affected performance of animals with perirhinal lesions at the 10-sec delay (the only delay in which their DNMS performance was above chance). They did not affect performance of animals with areas TH/TF lesions. Hippocampectomized animals were impaired at the 600-sec delay (the only delay at which prevention of active strategies would likely affect their behavior). ^ While lesions of areas TH/TF impaired spatial location memory and object-in-place memory, hippocampal lesions impaired only object-in-place memory. The pattern of results for perirhinal cortex lesions on the different task conditions indicated that this cortical area is not critical for spatial memory. ^ Finally, all three lesions impaired contextual recognition memory processes. The pattern of impairment appeared to result from the formation of only a global representation of the object and background, and suggests that all three areas are recruited for associating information across sources. ^ These results support the view that (1) the perirhinal cortex maintains storage of information about object and the context in which it is learned for a brief period of time, (2) areas TH/TF maintain information about spatial location and form associations between objects and their spatial relationship (a process that likely requires additional time) and (3) the hippocampal formation mediates associations between objects, their spatial relationship and the general context in which these associations are formed (an integrative function that requires additional time). ^

Los primeros sobrevivientes de la Shoa en Argentina : su imagen y memoria en la sociedad general y judía: 1945-50 (Primera Parte)

En la primera parte de esta indagación histórica se explora la imagen de los sobrevivientes en la sociedad general, con el trasfondo de la política inmigratoria argentina del peronismo entre 1946-50 que discriminaba a los refugiados judíos; después se indaga el lugar de la ayuda a esos sobrevivientes dentro de las prioridades de la comunidad judía organizada. Finalmente, se aborda un aspecto aún no investigado: el esfuerzo solitario de sus familiares residentes en Argentina para procurar, de organizaciones locales comunitarias e internacionales judías, el ingreso y socorro a los sobrevivientes que fueron localizados en los campos de personas desplazadas (DPs) y en otros lugares de Europa. Además se explora el impacto y memoria de la Shoa en los esfuerzos de reconstitución comunitaria a nivel institucional y educativa de la Kheila de Buenos Aires, realizados durante los primeros años de posguerra cuando la ayuda a los sobrevivientes que empezaban a arribar a Argentina quedó librada a la solitaria solidaridad de sus familiares locales y de asociaciones de coterráneos. Dada su extensión, aquí se publica la primera parte de este trabajo, el cual será completado en el número siguiente

Construcción de repositorios institucionales open source con Software Greenstone

Se aborda la construcción de repositorios institucionales open source con Software Greenstone. Se realiza un recorrido teórico y otro modélico desarrollando en él una aplicación práctica. El primer recorrido, que constituye el marco teórico, comprende una descripción, de: la filosofía open access (acceso abierto) y open source (código abierto) para la creación de repositorios institucionales. También abarca en líneas generales las temáticas relacionadas al protocolo OAI, el marco legal en lo que hace a la propiedad intelectual, las licencias y una aproximación a los metadatos. En el mismo recorrido se abordan aspectos teóricos de los repositorios institucionales: acepciones, beneficios, tipos, componentes intervinientes, herramientas open source para la creación de repositorios, descripción de las herramientas y finalmente, la descripción ampliada del Software Greenstone; elegido para el desarrollo modélico del repositorio institucional colocado en un demostrativo digital. El segundo recorrido, correspondiente al desarrollo modélico, incluye por un lado el modelo en sí del repositorio con el Software Greenstone; detallándose aquí uno a uno los componentes que lo conforman. Es el insumo teórico-práctico para el diseño -paso a paso- del repositorio institucional. Por otro lado, se incluye el resultado de la modelización, es decir el repositorio creado, el cual es exportado en entorno web a un soporte digital para su visibilización. El diseño del repositorio, paso a paso, constituye el núcleo sustantivo de aportes de este trabajo de tesina

Construcción de repositorios institucionales open source con Software Greenstone

Se aborda la construcción de repositorios institucionales open source con Software Greenstone. Se realiza un recorrido teórico y otro modélico desarrollando en él una aplicación práctica. El primer recorrido, que constituye el marco teórico, comprende una descripción, de: la filosofía open access (acceso abierto) y open source (código abierto) para la creación de repositorios institucionales. También abarca en líneas generales las temáticas relacionadas al protocolo OAI, el marco legal en lo que hace a la propiedad intelectual, las licencias y una aproximación a los metadatos. En el mismo recorrido se abordan aspectos teóricos de los repositorios institucionales: acepciones, beneficios, tipos, componentes intervinientes, herramientas open source para la creación de repositorios, descripción de las herramientas y finalmente, la descripción ampliada del Software Greenstone; elegido para el desarrollo modélico del repositorio institucional colocado en un demostrativo digital. El segundo recorrido, correspondiente al desarrollo modélico, incluye por un lado el modelo en sí del repositorio con el Software Greenstone; detallándose aquí uno a uno los componentes que lo conforman. Es el insumo teórico-práctico para el diseño -paso a paso- del repositorio institucional. Por otro lado, se incluye el resultado de la modelización, es decir el repositorio creado, el cual es exportado en entorno web a un soporte digital para su visibilización. El diseño del repositorio, paso a paso, constituye el núcleo sustantivo de aportes de este trabajo de tesina

Table 3: Comparison of freshwater species in Ob and Yenisei during the 1997 cruise

Phytoplankton biomass distribution (chlorophyll a, chl. a) and species composition (cell numbers) were investigated during three expeditions to the Kara Sea with "Akademik Boris Petrov" (BP) in 1997, 1999, and 2000. The distribution of biomass in the estuaries of Ob and Yenisei showed a similar range in 1997 (0.2 to 3.2 µg/l) and 2000 (0.4 to 3.5 ug/l); higher chl. a concentrations during these two years were found in Yenisei than in Ob. In 1999, phytoplankton biomass in the Ob and Ob Estuary was much higher than in 1997 and 2000, with maximum values above 10.0 ug chl. a/l. In 1999, biomass in Yenisei was lower (1.5 to ~5 ug/l) than in Ob but slightly higher than in 1997 and in 2000. During the expedition in 2000, the research area extended farther to the north, here, lowest phytoplankton biomass during all three years was found. Typical summer values for integrated chl.a biomass (surface to bottom) ranged between 6 and 20 mg m**-2. Strong differences existed in species composition in both rivers, the estuaries, and the open Kara Sea. In general, three or four different populations could be distinguished in surface waters: (1) freshwater diatoms together with bluegreen algae in both rivers, (2) centric and small pennate diatoms mainly brackish species in the estuaries, (3) north of 74°N, brackish/marine species dominated, i.e. in 1999 Thalassiosira cfpunctigera and Chaetoceros spp prevailed in the phytoplankton bloom in Ob. (4) At the northernmost, almost marine stations, a region with a more heterogeneous composition of unicellular plankton was encountered. We assume, we found different seasonal signals of phytoplankton development during 1997/2000 and 1999, respectively. However, the yearly fluctuation of freshwater runoff of both rivers seems to have the strongest influence on the timing and duration of phytoplankton blooms, species compositions and biomass standing stocks during summer.

Growth increments of the recent brachiopod Magellania venosa mechanically marked in Paso Comau and Comau Fjord, Chile, 2011/2012

Magellania venosa, the largest recent brachiopod, occurs in clusters and banks in population densities of up to 416 ind/m**2 in Comau Fjord, Northern Chilean fjord region. Below 15 m, it co-occurs with the mytilid Aulacomya atra and it dominates the benthic community below 20 m. To determine the question of why M. venosa is a successful competitor, the in situ growth rate of the brachiopod was studied and its overall growth performance compared with that of other brachiopods and mussels. The growth in length was measured between February 2011 and March 2012 after mechanical tagging and calcein staining. Settlement and juvenile growth were determined from recruitment tiles installed in 2009 and from subsequent photocensus. Growth of M. venosa is best described by the general von Bertalanffy growth function, with a maximum shell length (Linf) of 71.53 mm and a Brody growth constant (K) of 0.336/year. The overall growth performance (OGP index = 5.1) is the highest recorded for a rynchonelliform brachiopod and in the range of that for Mytilus chilensis (4.8-5.27), but lower than that of A. atra (5.74). The maximal individual production (PInd) is 0.29 g AFDM/ind/year at 42 mm shell length and annual production ranges from 1.28 to 89.25 g AFDM/year/m**2 (1-57% of that of A. atra in the respective fjords). The high shell growth rate of M. venosa, together with its high overall growth performance may explain the locally high population density of this brachiopod in Comau Fjord. However, the production per biomass of the population (P/B-ratio) is low (0.535) and M. venosa may play only a minor role in the food chain. Settling dynamics indicates that M. venosa is a pioneer species with low juvenile mortality. The coexistence of the brachiopod and bivalve suggests that brachiopod survival is affected by neither the presence of potential brachiopod predators nor that of space competitors (i.e. mytilids).

Porewater and solid-phase phosphorus geochemistry in surface sediments of sediment core GeoB9510-3, GeoB9518-4 and GeoB9519-6

Despite intensive research on the different domains of the marine phosphorus (P) cycle during the last decades, frequently discussed open questions still exist especially on controlling factors for the benthic behaviour of P and its general distribution in sediment-pore water systems. Steady state or the internal balance of all relevant physical and (bio)geochemical processes are amongst the key issues. In this study we present and discuss an extended data set from surface sediments recovered from three locations on the NW African continental slope. Pore water data and results from sequential sediment extractions give clear evidence to the well-known close relationship between the benthic cycles of P and iron. Accordingly, most of the dissolved phosphate must have been released by microbially catalyzed reductive dissolution of iron (oxhydr)oxides. However, rates of release and association of P and iron, respectively, are not directly represented in profiles of element specific sediment compositions. Results from steady-state based transport-reaction modelling suggest that particle mixing due to active bioturbation, or rather a physical net downward transport of P associated to iron (oxyhydr)oxides, is an essential process for the balance of the inspected benthic cycles. This study emphasizes the importance of balancing analytical data for a comprehensive understanding of all processes involved in biogeochemical cycles.

Topological invariance and spatial scaling of surface roughness in two highly eroded zones of Mexico: a comparative study

The Fractal Image Informatics toolbox (Oleschko et al., 2008 a; Torres-Argüelles et al., 2010) was applied to extract, classify and model the topological structure and dynamics of surface roughness in two highly eroded catchments of Mexico. Both areas are affected by gully erosion (Sidorchuk, 2005) and characterized by avalanche-like matter transport. Five contrasting morphological patterns were distinguished across the slope of the bare eroded surface of Faeozem (Queretaro State) while only one (apparently independent on the slope) roughness pattern was documented for Andosol (Michoacan State). We called these patterns ?the roughness clusters? and compared them in terms of metrizability, continuity, compactness, topological connectedness (global and local) and invariance, separability, and degree of ramification (Weyl, 1937). All mentioned topological measurands were correlated with the variance, skewness and kurtosis of the gray-level distribution of digital images. The morphology0 spatial dynamics of roughness clusters was measured and mapped with high precision in terms of fractal descriptors. The Hurst exponent was especially suitable to distinguish between the structure of ?turtle shell? and ?ramification? patterns (sediment producing zone A of the slope); as well as ?honeycomb? (sediment transport zone B) and ?dinosaur steps? and ?corals? (sediment deposition zone C) roughness clusters. Some other structural attributes of studied patterns were also statistically different and correlated with the variance, skewness and kurtosis of gray distribution of multiscale digital images. The scale invariance of classified roughness patterns was documented inside the range of five image resolutions. We conjectured that the geometrization of erosion patterns in terms of roughness clustering might benefit the most semi-quantitative models developed for erosion and sediment yield assessments (de Vente and Poesen, 2005).

The role of a firm's absorptive capacity and the technology transfer process in clusters: How effective are technology centres in low-tech clusters?

This paper analyses how the internal resources of small- and medium-sized enterprises determine access (learning processes) to technology centres (TCs) or industrial research institutes (innovation infrastructure) in traditional low-tech clusters. These interactions basically represent traded (market-based) transactions, which constitute important sources of knowledge in clusters. The paper addresses the role of TCs in low-tech clusters, and uses semi-structured interviews with 80 firms in a manufacturing cluster. The results point out that producer–user interactions are the most frequent; thus, the higher the sector knowledge-intensive base, the more likely the utilization of the available research infrastructure becomes. Conversely, the sectors with less knowledge-intensive structures, i.e. less absorptive capacity (AC), present weak linkages to TCs, as they frequently prefer to interact with suppliers, who act as transceivers of knowledge. Therefore, not all the firms in a cluster can fully exploit the available research infrastructure, and their AC moderates this engagement. In addition, the existence of TCs is not sufficient since the active role of a firm's search strategies to undertake interactions and conduct openness to available sources of knowledge is also needed. The study has implications for policymakers and academia.

A proposal for a Business Framework targeted at emerging business services and applications

Un Service Business Framework consiste en una serie de componentes interrelacionados que permiten la gestión de servicios de negocio a través de su ciclo de vida, desde su creación, descubrimiento y comparación, hasta su monetización (incluyendo un posible reparto de beneficios). De esta manera, el denominado FIWARE Business Framework trata de permitir a los usuarios de la plataforma FIWARE mejorar sus productos con funcionalidades de búsqueda, describrimiento, comparación, monetización y reparto de beneficios. Para lograr este objetivo, el Business Framework de FIWARE proporciona la especificación abierta y las APIs de una serie de components (denominados \Generic Enablers" en terminología FIWARE), junto con una implementación de referencia de las mismas pueden ser facilmente integradas en los sitemas existentes para conseguir aplicaciones con valor a~nadido. Al comienzo de este trabajo de fin de master, el Business Framework de FIWARE no era lo suficientemente maduro como para cubrir los requisitos de sus usuarios, ya que ofrecía modelos demasiado generales y dejaba algunas funcionalidades clave para ser implementadas por los usuarios. Para solucionar estos problemas, el principal objectivo desarrollado en el contexto de este trabajo de fin de master ha consistido en mejorar y evolucionar el Business Framework de FIWARE para dar respuesta a las demandas de sus usuarios. Para alcanzar el pricipal objetivo propuesto, el Business Framework de FIWARE ha sido evaluado usando la información proporcionada por los usuarios de la plataforma, principalmente PyMEs y start-ups que usan este framework en sus soluciones, con el objetivo de obtener una lista de requisitos y de dise~nar a partir de éstos un roadmap de evolución a 6 meses. Después, los diferentes problemas identificados se han tratado uno por uno dando en cada caso una solución capaz de cubrir los requisitos de los usuarios. Finalmente, se han evaluado los resultados obtenidos en el proyecto integrando el Business Framework desarrollado con un sistema existente para la gestión de datos de consusmo energético, construyendo lo que se ha denominado Mercado de Datos de Consumo Energético. Esto además ha permitido demostrar la utilidad del framework propuesto para evolucionar una plataforma de datos abiertos bien conocida como es CKAN a un verdadero mercado de datos.---ABSTRACT---Service Business Frameworks consist on a number of interrelated components that support the management of business services across their whole lifecycle, from their creation, publication, discovery and comparison, to their monetization (possibly including revenue settlement and sharing). In this regard, the FIWARE Business Framework aims at allowing FIWARE users to enhance their solutions with search, discovery, comparison, monetization and revenue settlement and sharing features. To achieve this objective, the FIWARE Business Framework provides the open specification and APIs of a comprehensive set of components (called Generic Enablers in FIWARE terminology), along with a reference implementation of these APIs,, that can be easily integrated with existing systems in order to create value added applications. At the beginning of the current Master's Thesis, the FIWARE Business Framework was not mature enough to cover the requirements of the its users, since it provided too general models and leaved some key functionality to be implemented by those users. To deal with these issues, the main objective carried out in the context of this Master's Thesis have been enhancing and evolving the FIWARE Business Framework to accomplish with the demands of its users. For achieving the main objective of this Master's Thesis, the FWARE Business Framework has been evaluated using the feedback provided by FIWARE users, mainly SMEs and start-ups, actually using the framework in their solutions, in order to determine a list of requirements and to design a roadmap for the evolution and improvement of the existing framework in the next 6 months. Then, the diferent issues detected have been tackle one by one enhancing them, and trying to give a solution able to cover users requirements. Finally, the results of the project have been evaluated by integrating the evolved FIWARE Business Framework with an existing system in charge of the management of energy consumption data, building what has been called the Energy Consumption Data Market. This has also allowed demonstrating the usefulness of the proposed business framework to evolve CKAN, a renowned open data platform, into an actual, fully- edged data market.

Accessing and managing open medical resources in Africa over the Internet

Recent commentaries have proposed the advantages of using open exchange of data and informatics resources for improving health-related policies and patient care in Africa. Yet, in many African regions, both private medical and public health information systems are still unaffordable. Open exchange over the social Web 2.0 could encourage more altruistic support of medical initiatives. We have carried out some experiments to demonstrate the feasibility of using this approach to disseminate open data and informatics resources in Africa. After the experiments we developed the AFRICA BUILD Portal, the first Social Network for African biomedical researchers. Through the AFRICA BUILD Portal users can access in a transparent way to several resources. Currently, over 600 researchers are using distributed and open resources through this platform committed to low connections.

Dinámicas de ocupación urbana del Anillo Verde metropolitano, desde sus orígenes en el Plan General del Área Metropolitana de Madrid de 1963 hasta el Plan General de Ordenación Urbana de 1997

El Anillo Verde metropolitano, definido por el Plan General de Ordenación Urbana del Área Metropolitana de Madrid en 1963 siguiendo los modelos planteados por la cultura urbanística internacional, como armadura de la estructura urbana del AMM, espacio protagonista dentro del sistema de espacios libres, lugar de uso público destinado al recreo y contacto con la naturaleza de la población madrileña, se convierte en realidad en una reserva de suelo que va entrando en juego motivado por las alianzas entre el poder institucional y la clase social dominante actuando al margen del planeamiento, poniendo en evidencia la escasez de recursos legales y culturales disponibles para la salvaguarda de los intereses comunes y, donde los condicionantes geográficos y naturales del territorio madrileño han influido decisivamente en la especialización funcional y espacial del Área Metropolitana de Madrid. Así pues considerando esta idea como HIPÓTESIS, el objetivo de la TESIS sería demostrarla, para lo cual se hace necesario primero, acotar espacial y temporalmente el objeto de estudio, es decir, del Anillo Verde metropolitano1, segundo, contextualizar histórica y disciplinarmente los presupuestos teóricos que conformaban la idea del Anillo Verde, tercero, reconocer, localizar y documentar las piezas que han ido materializando la ocupación urbana del Anillo Verde, clasificándolas según parámetros temporales, funcionales, urbanísticos y, formales, lo que permite analizar la geografía, uso, instrumentación y forma de su transformación a escala general metropolitana y, cuarto, profundizar a modo de comprobación a escala municipal y urbana en dos escenarios representativos del conjunto metropolitano: el municipio de Pozuelo de Alarcón y el distrito de Hortaleza-Barajas. El contenido del documento se divide en tres bloques, el bloque I, se centra en las bases teóricas, el bloque II sitúa el hilo argumental de la tesis a escala metropolitana y el bloque III comprueba el fenómeno a escala municipal y urbana. De esta forma, se comienza por la comprensión del significado del concepto del Anillo Verde, que va más allá de la dimensión instrumental asignada de límite y contención urbana frente al crecimiento de la ciudad industrial de principios del siglo XX, basada en la descentralización de la ciudad tradicional, para adquirir un significado más complejo, como gran espacio de reserva y salvaguarda de valores naturales y culturales que se expresaban en su territorio y que permitirían alcanzar el equilibrio entre la ciudad y sus habitantes, es decir, entre el hombre y el espacio que habita. Se hace un recorrido por las principales corrientes urbanísticas que se van nutriendo de distintas disciplinas (economía, sociología, geografía, biología, ecología) para plantear teorías que permitieran materializar un nuevo orden urbano según principios de equidad social, económica y ambiental, en una secuencia donde Europa y Estados Unidos realizaban un constante intercambio -el movimiento de la Ciudad Jardín o el Regionalismo, que dieron paso a propuestas como el Greater London o el Gran Berlín, donde la figura del Anillo Verde tenía un papel protagonista, y del que también participaría nuestro país y la ciudad de Madrid, con modelos regionales como el Plan Besteiro y urbanos como el Plan Bidagor, antecedentes directos del Plan General de Ordenación Urbana del Área Metropolitana de Madrid de 1963 que pone en marcha la ordenación del crecimiento metropolitano de Madrid. El hilo argumental de la tesis se organiza en una doble aproximación: un acercamiento a escala metropolitana a partir del reconocimiento del modelo de ciudad definido en los distintos planes generales que acompañaron el desarrollo metropolitano (municipio de Madrid y de los siete términos municipales que rodeaban a este y que tenían suelo destinado a Anillo Verde), haciendo referencia además a las relaciones con el planeamiento regional, concretando en una escala de aproximación municipal que avanza hasta la interpretación urbana detallada. El primer acercamiento tiene lugar en el bloque II y se organiza en tres capítulos. El capítulo 4 se dedica al punto obligado de partida de la geografía local, describiendo las características biofísicas de los terrenos que formaban parte del Anillo Verde, que han marcado históricamente la forma de aprovechamiento del territorio, desde las extensiones de bosques mediterráneos al norte y al oeste continuación del Monte del Pardo, a los distintos tipos de cultivo que se adaptaban al sustrato geológico y la forma del terreno (de las suaves ondulaciones de sedimentos arcósicos al norte a las extensas plataformas arenosas y yesíferas del sur), además de las zonas de huertos aprovechando las depresiones y los cursos de agua (arroyo del Monte Carmelo, arroyo de Valdebebas, arroyo del Quinto, arroyo del Santo, arroyo Butarque, arroyo Meaques y arroyo Pozuelo). Una vez reconocida la realidad física, el capítulo 5, avanza en la descripción de los distintos modelos de ciudad propuestos desde el planeamiento urbanístico, en sus distintas escalas, la regional y la municipal, como respuesta a la coyuntura social, económica y política que ha caracterizado el proceso de ocupación del Anillo Verde al compás de la construcción del AMM. Se han reunido las propuestas de planeamiento municipal de los distintos municipios que disponían de terreno calificado como Anillo Verde: Madrid, Coslada, Getafe, Leganés, Alcorcón, Boadilla del Monte y Pozuelo de Alarcón. Además se han incorporado las distintas propuestas de ordenación territorial que han servido de referencia al planeamiento municipal, en todas sus versiones, desde las sectoriales, de mayor éxito y apoyo institucional, a los distintos intentos de ordenación integral, de mayor complejidad pero de menor calado, precisamente por la dificultad de consenso entre la ordenación física y el desarrollo económico, entre los intereses privados y el beneficio público. El primer horizonte, comienza con la formulación del Plan General de Ordenación Urbana del Área Metropolitana de Madrid de 1963, su desarrollo y la puesta en marcha de los primeros planes municipales en la década de los años setenta, donde se comprueba la necesidad de un marco regional que “ordene” el territorio de forma integral y sirva de referencia a las actuaciones sectoriales que habían marcado el primer desarrollo metropolitano. El segundo, se sitúa dos décadas más tarde con la aprobación del Plan General de Ordenación Urbana de Madrid de 1985 y el conjunto de planes municipales de los términos limítrofes, que siguen su filosofía de austeridad en cuanto a crecimiento territorial. El tercero se inicia en 1997 con la siguiente generación de planes de corte neoliberal que imponen un modelo territorial basado en las grandes operaciones metropolitanas de centralidad, infraestructuras y equipamiento, que consumen de forma indiscriminada la totalidad del territorio madrileño. Será en el último capítulo del segundo bloque (capítulo 6) donde se represente gráficamente a escala metropolitana y se analicen las 229 piezas que han ido colmatando el espacio destinado a Anillo Verde, según los parámetros de estudio, en base a las cuales se plantean las primeras conclusiones generales de la tesis, poniendo de manifiesto que las alianzas entre los agentes soberanos en la construcción de la ciudad y su entorno han trasgredido sucesivamente las determinaciones del Planeamiento en su definición de modelo de ciudad y territorio, acusando la carencia de recursos instrumentales y jurídicos que alentaron el proceso de su desmantelamiento, y revelando la influencia de los condicionantes geográficos y naturales en la especialización funcional y segregación social en el conjunto del Área Metropolitana de Madrid. Se remata el discurso metropolitano con una batería de conclusiones que interpretan el fenómeno de ocupación del anillo de verdor metropolitano confirmando las hipótesis iniciales, reconociendo los valores medioambientales y culturales trasgredidos, sus diversos actores, las numerosas operaciones urbanísticas desarrolladas con distintos usos y envergadura, así como los instrumentos de planeamiento utilizados, en base a las cuales se materializa la construcción del AMM según un modelo extendido (spread), dibujando una mancha de aceite (o grase-spots según Geddes) que precisamente había querido evitarse desde el planeamiento urbanístico con la definición de un Anillo Verde, espacio inmune a la edificación, que se aleja de su papel estructurante (equilibrador entre la ciudad y sus habitantes) para convertirse en armadura de la estructura comunicativa, que una vez consolidada se convierte en la mejor aliada de la máquina inmobiliaria. El último paso, se desarrolla en el bloque III que se divide en los capítulo 7,8 y 9 y supone la comprobación de lo descrito en el conjunto de escala metropolitana, en dos aspectos fundamentales, la falta de consideración por los valores culturales y medioambientales que han modelado el territorio, imprimiéndole un carácter singular y específico y, la estructura del dominio del suelo, donde se reconoce de forma precisa el grupo social y los agentes encargados en cada momento de comercializar los suelos del anillo, que bajo el paraguas de la urgencia social y el engañoso beneficio popular, obtienen importantes beneficios económicos. Con esa intención, se da un salto hacia la escala municipal y urbana, seleccionando dos escenarios de estudio, el municipio de Pozuelo de Alarcón, que representa la materialización del crecimiento suburbano de la élite madrileña ocupando las zonas de mayor valor ecológico del anillo, y el distrito de Hortaleza-Barajas que ofrece su territorio a las grandes operaciones metropolitanas, apoyándose en el eje de actividad marcado por la conexión Madrid-Barcelona y el sistema aeroportuario de escala global, ambos situados al norte de la línea de borde entre la Sierra y la Mancha, ocupando por tanto los lugares más valiosos de la geografía madrileña (estructura funcional anticipada por Bidagor en 1946 en su modelo de ciudad adaptada al territorio madrileño) Una vez descrito este proceso trasgresor de límites, de normas, de conductas, y desde una perspectiva del fenómeno suficientemente documentada, en el capítulo 10, se realiza una reflexión sobre la incidencia real de la propuesta urbanística del Anillo Verde en la construcción del AMM, de la misma forma que se sugieren nuevos roles al planeamiento en un formato intencionado de largo recorrido en oposición a lo inmediato y circunstancial, que permita hacer una nueva lectura de los presupuestos teóricos que conformaban la idea del Anillo Verde, espacio articulador (medioambiental, social y cultural) del territorio madrileño. ABSTRACT The Metropolitan Greenbelt was defined by the 1963 Master Plan for the Madrid Metropolitan Area (MMA), following established international models of urban development, as the structural framework of the MMA, the principal open space within its network of open spaces and a public area of recreation and contact with nature for the residents of Madrid. In reality, however, it ha become a reserve of land in which various alliances between the institutional authorities and the dominant social class have been operating on the margin of the original plan, exposing a scarcity of legal and cultural resources for the safeguarding of common interests, and in which the geographical and natural characteristics of the territory itself have come to play an influential role in the functional specialization and spatial segregation of the MMA. With that idea as its HYPOTHESIS, the aim of this THESIS is to demonstrate its reality. The first step in this is to delineate, temporally and spatially, the object of study; i.e. the Metropolitan Greenbelt2. The second is to contextualize historically and disciplinarily those theoretical ideas which conform to the greenbelt concept. The third is to acknowledge, locate and document the elements which have characterized the urban occupation of the Greenbelt and classify these according to the parameters of time, function, urban development and form, which in turn would enable the geography, use, instrumentation and form of its transformation to be analysed on a general metropolitan scale. The fourth step, as a method of verification, is an in-depth analysis of two representative settings within the metropolitan network: the municipality of Pozuelo de Alarcón and the Hortaleza-Barajas district. The content of the document is divided into three parts. Part I focuses on the study’s theoretical foundations, Part II establishes a line of argument at the metropolitan level and Part III examines the phenomenon from a municipal and urban perspective. The thesis, then, begins with a study of the greenbelt concept itself and its meaning, which is far more complex than the accepted instrumental dimension of limiting and containing urbanization in response to the growth of the industrial city of the early 20th century, and which is based on a decentralization of the traditional city. This wider purpose is the setting aside of a large reserved space to safeguard the natural and cultural values of the region and thereby achieve a balance between the city and its residents; that is to say, between man and the space he inhabits. The principal currents of thought in urban planning will then be examined. These have drawn upon a variety of disciplines (economics, sociology, geography, biology, ecology) to develop theories for establishing a new urban order according to the principles of social, economic and environmental equity, and have involved a constant interchange between Europe and the United States. Thus, the City Garden and Regionalist movements would clear the way for proposals such as Greater London and Great Berlin, Chicago and Washington, in which the greenbelt would play a fundamental role. The participation of our own country and the city of Madrid is also discussed, through regional models such as the Besteiro Plan and urban ones like the Bidagor Plan, direct forerunners of 1963’s General Organizational Plan for the Madrid Metropolitan Area, which would set into motion the organization of Madrid’s metropolitan growth. The line of argument followed in this thesis is two-fold: first, an examination of metropolitan development in keeping with the city model as defined in the various General Plans for the development of both the municipality of Madrid and the seven surrounding municipalities which have land designated for its Greenbelt; and second, an examination of this growth in relation to Regional Planning measures, is detailed on a smaller scale (municipal and district), where the conditioning factors affecting the land property structure and the network of biophysical units may be analysed in depth. The first of these is dealt with in Part II and organized into three chapters (4, 5 and 6). Chapter 4 is dedicated to the obligatory starting point of the geographical setting itself. The biophysical characteristics of the territories set aside for the Greenbelt, and which historically have played a role in the area’s exploitation, are described here. These range from expanses of Mediterranean woodland to the north and west of Monte del Pardo to the various types of farmland that have been adapted to the geological substratum and the contours of the terrain (gentle undulations of arkosic sediment in the north, and wide sandy and gypsiferous tableland in the south), as well as orchards planted in low valleys and along watercourses (the creeks of Monte Carmelo, Valdebebas, Quinto, Santo, Butarque, Meaques and Pozuelo). Once this physical reality ha been detailed, in Chapter 5 will examine the various city models proposed by urban planners, both regionally and municipally, in response to the confluence of social, economic and political interests that have characterized the process of occupation in the Greenbelt area during the construction of the MMA. Municipal planning proposals will be collected and examined for the various municipalities which have land designated for the Greenbelt: Madrid, Coslada, Getafe, Leganés, Alcorcón, Boadilla del Monte and Pozuelo de Alarcón. Furthermore, the various territorial organization proposals which have served as references for municipal planning will also be addressed here, in all of their versions –from the sectorial, which have met with more success and institutional approval, to the many attempts at integration, which have been more complex but less influential, precisely for the difficulty of reconciling physical organization with economic development, and private interest with public benefit. The first period in this process was the development of the General Plan of 1963, followed by the first municipal development plans of the 1970s, in which the need for a regional framework that “organized” the territory in an integral fashion was defined. This would serve as a reference for the sectorial actions that marked the metropolitan area’s initial development. The second came two decades later with the approval of the General Plan of 1985, and the network of municipal plans for the surrounding communities, which followed the same philosophy of austerity with regard to territorial growth. The third would begin to take form in 1997, as a new generation of neo-liberal development plans imposed a territorial model based on centralized large-scale metropolitan operations of infrastructure and equipment, which would indiscriminately consume the totality of Madrid’s land. At the end of the Part II, in Chapter 6, the metropolitan area will be represented graphically and the 229 pieces that have been gradually encroaching upon land designated for the Greenbelt will be analysed. This analysis will be carried out according to the parameters defined for the study, and the first general conclusions of the thesis will be based on its findings. It will show how alliances between the various governing authorities in the construction of the city and its environment have successively violated established plans with regard to the definitions of city and territory, how shortages of instrumental and judicial resources have accentuated the dismantling process, and how natural and geographical factors have influenced functional specialization and social segregation in the Madrid Metropolitan Area. The final step, detailed in Part III, will address two fundamental aspects of what has just been described: the lack of consideration for the cultural and environmental values which have shaped this territory and imprinted upon it a specific and unique character; and the structure of land domination, with a precise identification of the social group and agents responsible at each stage of the Greenbelt’s commercialization, who, under an umbrella of social urgency and deceptive public benefit, have used it to obtain substantial financial rewards. For this purpose, a closer look is taken at two specific areas: the municipality of Pozuelo de Alarcón, representative of the suburban growth of an elite population which has occupied the Greenbelt areas of the greatest ecological value; and the Hortaleza-Barajas district, which has offered its territory to large metropolitan business interests, based on activities centred on the connection between Madrid and Barcelona and the system of international air travel. Both of these settings are located to the north of the line which divides the Sierra from La Mancha, and thus occupy the most valuable land in the Madrid region (a functional structure anticipated by Bidagor in 1946, with his city model adapted to the territory of Madrid). Finally, an attempt will be made to interpret the phenomenon of metropolitan Greenbelt occupation, confirming initial hypotheses, specifying the environmental and cultural values that have been violated, and identifying the various players involved, as well as numerous urbanization operations of varying sizes and interests, and the instruments of planning they have used. It will be seen from this that the construction of the MMA has in fact followed a “spread” model, a “grease spot” (as Geddes calls it) which, from the outset of the planning process and according to the definition of a greenbelt as a construction-free zone, was precisely to be avoided. This structural role (to provide a balance between a city and its residents) has thus been abandoned and the Greenbelt converted instead into a communicative framework which, once consolidated, has become the greatest ally of the real estate machine. After this process of violating limits, norms and established behaviour has been described and solidly documented, a reflection will be made on the real influence of the Greenbelt proposal in the construction of the MMA. At the same time, new roles will be suggested for future planning, roles which are deliberate and long term, in opposition to the immediate and circumstantial. This will enable a new interpretation of the theoretical principles behind the greenbelt concept, a space designed to connect the territory of Madrid environmentally, socially and culturally.

Linking genome and proteome by mass spectrometry: Large-scale identification of yeast proteins from two dimensional gels

The function of many of the uncharacterized open reading frames discovered by genomic sequencing can be determined at the level of expressed gene products, the proteome. However, identifying the cognate gene from minute amounts of protein has been one of the major problems in molecular biology. Using yeast as an example, we demonstrate here that mass spectrometric protein identification is a general solution to this problem given a completely sequenced genome. As a first screen, our strategy uses automated laser desorption ionization mass spectrometry of the peptide mixtures produced by in-gel tryptic digestion of a protein. Up to 90% of proteins are identified by searching sequence data bases by lists of peptide masses obtained with high accuracy. The remaining proteins are identified by partially sequencing several peptides of the unseparated mixture by nanoelectrospray tandem mass spectrometry followed by data base searching with multiple peptide sequence tags. In blind trials, the method led to unambiguous identification in all cases. In the largest individual protein identification project to date, a total of 150 gel spots—many of them at subpicomole amounts—were successfully analyzed, greatly enlarging a yeast two-dimensional gel data base. More than 32 proteins were novel and matched to previously uncharacterized open reading frames in the yeast genome. This study establishes that mass spectrometry provides the required throughput, the certainty of identification, and the general applicability to serve as the method of choice to connect genome and proteome.

Ferredoxin and ferredoxin–heme maquettes

A 16-amino acid residue peptide derived from a consensus motif of natural ferredoxins incorporates a tetranuclear iron sulfur cluster under physiological conditions. Successful assembly of the [4Fe–4S]2+/1+ cluster within a monomeric peptide was demonstrated using size exclusion chromatography, UV-visible, visible CD, and cryogenic EPR spectroscopies. The robustness of [4Fe–4S]2+/1+ formation was tested using peptides with either the ligating cysteine exchanged for alanine or with the intervening amino acids replaced by glycine. The small size of the peptide allows for modular incorporation into more complex protein structures. In one larger structure, we describe a tetra-α-helix bundle that self-assembles both iron–sulfur clusters and hemes, thereby demonstrating feasibility for the general synthesis of maquettes containing multiple, juxtaposed redox cofactors. This is a motif common to the catalytic sites of native oxidoreductases.