SUMO-SPECIFIC PROTEASE 1 CONTROLS LYMPHOID DEVELOPMENT THROUGH REGULATION OF SUMOYLATION/ACETYLATION SWITCH IN STAT5

SUMOylation has emerged as an important regulatory mechanism for protein function. SUMO-specific proteases (SENPs) are essential for removing SUMO from conjugated proteins in many different systems, but the physiological functions of SENPs are poorly understood. STAT5 (Signal Transducer and Activator of Transcription 5) plays a critical role in the development of lymphoid cells. However, it is not known whether STAT5 is regulated by the SUMOylation pathway. Here, we showed that SUMOylated STAT5 is accumulated in SENP1-/- lymphoid precursors. SENP1 deficiency results in severe defects in early T and B cell development, similar to that observed in mice harboring a complete inactivation of STAT5. Because STAT5 is SUMOylated and acetylated at the same lysine residue, SENP1 deficiency blocks STAT5 in the SUMOylation state, resulting in diminished STAT5 acetylation and phosphorylation, and defective lymphoid development. Thus, our results reveal a novel function of SENP1 in the regulation of early lymphoid development via an acetylation/SUMOylation switch in STAT5.

Phenotypic and genotypic analysis of mouse hepatitis virus (JHM) complementation group A temperature-sensitive mutants

Temperature sensitive (ts) mutant viruses have helped elucidate replication processes in many viral systems. Several panels of replication-defective ts mutants in which viral RNA synthesis is abolished at the nonpermissive temperature (RNA$\sp{-})$ have been isolated for Mouse Hepatitis Virus, MHV (Robb et al., 1979; Koolen et al., 1983; Martin et al., 1988; Schaad et al., 1990). However, no one had investigated genetic or phenotypic relationships between these different mutant panels. In order to determine how the panel of MHV-JHM RNA$\sp{-}$ ts mutants (Robb et al., 1979) were genetically related to other described MHV RNA$\sp{-}$ ts mutants, the MHV-JHM mutants were tested for complementation with representatives from two different sets of MHV-A59 ts mutants (Koolen et al., 1983; Schaad et al., 1990). The three ts mutant panels together were found to comprise eight genetically distinct complementation groups. Of these eight complementation groups, three complementation classes are unique to their particular mutant panel; genetically equivalent mutants were not observed within the other two mutant panels. Two complementation groups were common to all three mutant panels. The three remaining complementation groups overlapped two of the three mutant sets. Mutants MHV-JHM tsA204 and MHV-A59 ts261 were shown to be within one of these overlapping complementation groups. The phenotype of the MHV-JHM mutants within this complementation class has been previously characterized (Leibowitz et al., 1982; Leibowitz et al, 1990). When these mutants were grown at the permissive temperature, then shifted up to the nonpermissive temperature at the start of RNA synthesis, genome-length RNA and leader RNA fragments accumulated, but no subgenomic mRNA was synthesized. MHV-A59 ts261 produced leader RNA fragments identical to those observed with MHV-JHM tsA204. Thus, these two MHV RNA$\sp{-}$ ts mutants that were genetically equivalent by complementation testing were phenotypically similar as well. Recombination frequencies obtained from crosses of MHV-A59 ts261 with several of the gene 1 MHV-A59 mutants indicated that the causal mutation(s) of MHV-A59 ts261 was located near the overlapping junction of ORF1a and ORF1b, in the 3$\sp\prime$ end of ORF1a, or the 5$\sp\prime$ end of ORF1b. Sequence analysis of this junction and 1400 nucleotides into the 5$\sp\prime$ end of ORF1b of MHV-A59 ts261 revealed one nucleotide change from the wildtype MHV-A59. This substitution at nucleotide 13,598 (A to G) was a silent mutation in the ORF1a reading frame, but resulted in an amino acid change in ORF1b gene product (I to V). This amino acid change would be expressed only in the readthrough translation product produced upon successful ribosome frameshifting. A revertant of MHV-A59 ts261 (R2) also retained this guanidine residue, but had a second substitution at nucleotide 14,475 in ORF1b. This mutation results in the substitution of valine for an isoleucine.^ The data presented here suggest that the mutation in MHV-A59 ts261 (nucleotide 13,598) would be responsible for the MHV-JHM complementation group A phenotype. A second-site reversion at nucleotide 14,475 may correct this defect in the revertant. Sequencing of gene 1 immediately upstream of nucleotide 13,296 and downstream of nucleotide 15,010 must be conducted to test this hypothesis. ^

Intussusceptive microvascular growth: a common alternative to capillary sprouting.

Intussusceptive capillary growth represents a new principle for microvascular growth as described in the lungs of growing rats. According to this concept, the capillary network expands by the formation of slender transcapillary tissue pillars, which give rise to new vascular meshes. The process was first observed in Mercox casts of the lung microvasculature, which revealed the existence of multiple tiny holes with diameters around 1.5 microns. Consecutive transmission electron microscopic investigation of serial sections demonstrated that the holes corresponded to slender tissue pillars (Burri and Tarek, 1990). The corrosion cast technique thus appears to be an adequate screening method for intussusceptive growth. In the present investigation, Mercox casts of various vascular systems, namely, those of the eye, submandibular gland, heart, liver, stomach, small and large intestine, trachea, kidney, uterus and ovary were prepared from rats aged between 4 and 9 weeks in order to screen them for the existence of the typical tiny holes representing tissue pillars. In all organs investigated, these structures were observed in various locations to a variable degree. They were mainly encountered within dilated vascular segments or at triple or quadruple branching points of the circulation. Even in capillary networks with a three-dimensional arrangement could these pillars be detected. Intussusception thus appears to be a principle of growth appertaining to many vascular systems.

Systematic reviews published in higher impact clinical journals were of higher quality.

OBJECTIVES To compare the methodological quality of systematic reviews (SRs) published in high- and low-impact factor (IF) Core Clinical Journals. In addition, we aimed to record the implementation of aspects of reporting, including Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram, reasons for study exclusion, and use of recommendations for interventions such as Grading of Recommendations Assessment, Development and Evaluation (GRADE). STUDY DESIGN AND SETTING We searched PubMed for systematic reviews published in Core Clinical Journals between July 1 and December 31, 2012. We evaluated the methodological quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. RESULTS Over the 6-month period, 327 interventional systematic reviews were identified with a mean AMSTAR score of 63.3% (standard deviation, 17.1%), when converted to a percentage scale. We identified deficiencies in relation to a number of quality criteria including delineation of excluded studies and assessment of publication bias. We found that SRs published in higher impact journals were undertaken more rigorously with higher percentage AMSTAR scores (per IF unit: β = 0.68%; 95% confidence interval: 0.32, 1.04; P < 0.001), a discrepancy likely to be particularly relevant when differences in IF are large. CONCLUSION Methodological quality of SRs appears to be better in higher impact journals. The overall quality of SRs published in many Core Clinical Journals remains suboptimal.

High-Frequency in Situ Optical Measurements During a Storm Event: Assessing Relationships Between Dissolved Organic Matter, Sediment Concentrations, and Hydrologic Processes

Dissolved organic matter (DOM) dynamics during storm events has received considerable attention in forested watersheds, but the extent to which storms impart rapid changes in DOM concentration and composition in highly disturbed agricultural watersheds remains poorly understood. In this study, we used identical in situ optical sensors for DOM fluorescence (FDOM) with and without filtration to continuously evaluate surface water DOM dynamics in a 415 km(2) agricultural watershed over a 4 week period containing a short-duration rainfall event. Peak turbidity preceded peak discharge by 4 h and increased by over 2 orders of magnitude, while the peak filtered FDOM lagged behind peak turbidity by 15 h. FDOM values reported using the filtered in situ fluorometer increased nearly fourfold and were highly correlated with dissolved organic carbon (DOC) concentrations (r(2) = 0.97), providing a highly resolved proxy for DOC throughout the study period. Discrete optical properties including specific UV absorbance (SUVA(254)), spectral slope (S(290-350)), and fluorescence index (FI) were also strongly correlated with in situ FDOM and indicate a shift toward aromatic, high molecular weight DOM from terrestrially derived sources during the storm. The lag of the peak in FDOM behind peak discharge presumably reflects the draining of watershed soils from natural and agricultural landscapes. Field and experimental evidence showed that unfiltered FDOM measurements underestimated filtered FDOM concentrations by up to similar to 60% at particle concentrations typical of many riverine systems during hydrologic events. Together, laboratory and in situ data provide insights into the timing and magnitude of changes in DOM quantity and quality during storm events in an agricultural watershed, and indicate the need for sample filtration in systems with moderate to high suspended sediment loads.

An automatic documentation generator for (C)LP - Reference manual

Lpdoc is an automatic program documentation generator for (C)LP systems. Lpdoc generates a reference manual automatically from one or more source files for a logic program (including ISO-Prolog, Ciao, many CLP systems, ...). It is particularly useful for documenting library modules, for which it automatically generates a description of the module interface. However, lpdoc can also be used quite successfully to document full applications and to generate nicely formatted plain ascii "readme" files. A fundamental advantage of using lpdoc to document programs is that it is much easier to maintain a true correspondence between the program and its documentation, and to identify precisely to what version of the program a given printed manual corresponds. The quality of the documentation generated can be greatly enhanced by including within the program text: • assertions (types, modes, etc. ...) for the predicates in the program, and • machine-readable comments (in the "literate programming" style). The assertions and comments included in the source file need to be written using the Ciao system assertion language. A simple compatibility library is available to make traditional (constraint) logic programming systems ignore these assertions and comments allowing normal treatment of programs documented in this way. The documentation is currently generated in HTML or texinf o format. From the texinf o output, printed and on-line manuals in several formats (dvi, ps, info, etc.) can be easily generated automatically, using publicly available tools, lpdoc can also generate 'man' pages (Unix man page format) as well as brief descriptions in html or emacs info formats suitable for inclusion in an on-line index of applications. In particular, lpdoc can create and maintain fully automatically WWW and info sites containing on-line versions of the documents it produces. The lpdoc manual (and the Ciao system manuals) are generated by lpdoc. Lpdoc is distributed under the GNU general public license. Note: lpdoc is fully supported on Linux, Mac OS X, and other Un*x-like systems. Due to the use of several Un*x-related utilities, some documentation back-ends may require Cygwin under Win32. This documentation corresponds to version 3.0 (2011/7/7, 16:33:15 CEST).

Massively parallelizable list-mode reconstruction using a Monte Carlo-based elliptical Gaussian model

Purpose: A fully three-dimensional (3D) massively parallelizable list-mode ordered-subsets expectation-maximization (LM-OSEM) reconstruction algorithm has been developed for high-resolution PET cameras. System response probabilities are calculated online from a set of parameters derived from Monte Carlo simulations. The shape of a system response for a given line of response (LOR) has been shown to be asymmetrical around the LOR. This work has been focused on the development of efficient region-search techniques to sample the system response probabilities, which are suitable for asymmetric kernel models, including elliptical Gaussian models that allow for high accuracy and high parallelization efficiency. The novel region-search scheme using variable kernel models is applied in the proposed PET reconstruction algorithm. Methods: A novel region-search technique has been used to sample the probability density function in correspondence with a small dynamic subset of the field of view that constitutes the region of response (ROR). The ROR is identified around the LOR by searching for any voxel within a dynamically calculated contour. The contour condition is currently defined as a fixed threshold over the posterior probability, and arbitrary kernel models can be applied using a numerical approach. The processing of the LORs is distributed in batches among the available computing devices, then, individual LORs are processed within different processing units. In this way, both multicore and multiple many-core processing units can be efficiently exploited. Tests have been conducted with probability models that take into account the noncolinearity, positron range, and crystal penetration effects, that produced tubes of response with varying elliptical sections whose axes were a function of the crystal's thickness and angle of incidence of the given LOR. The algorithm treats the probability model as a 3D scalar field defined within a reference system aligned with the ideal LOR. Results: This new technique provides superior image quality in terms of signal-to-noise ratio as compared with the histogram-mode method based on precomputed system matrices available for a commercial small animal scanner. Reconstruction times can be kept low with the use of multicore, many-core architectures, including multiple graphic processing units. Conclusions: A highly parallelizable LM reconstruction method has been proposed based on Monte Carlo simulations and new parallelization techniques aimed at improving the reconstruction speed and the image signal-to-noise of a given OSEM algorithm. The method has been validated using simulated and real phantoms. A special advantage of the new method is the possibility of defining dynamically the cut-off threshold over the calculated probabilities thus allowing for a direct control on the trade-off between speed and quality during the reconstruction.

New concepts and techniques for the development of high-efficiency concentrating photovoltaic modules

El interés por los sistemas fotovoltaicos de concentración (CPV) ha resurgido en los últimos años amparado por el desarrollo de células multiunión de muy alta eficiencia basadas en semiconductores de los grupos III-V. Estas células han permitido obtener módulos de concentración con eficiencias que prácticamente duplican las del panel plano y que llegan al 35% en los módulos récord. Esta tesis está dedicada al diseño y la implementación experimental de nuevos conceptos que permitan obtener módulos CPV que no sólo alcancen una eficiencia alta en condiciones estándar sino que, además, sean lo suficientemente tolerantes a errores de montaje, seguimiento, temperatura y variaciones espectrales para que la energía que producen a lo largo del año sea máxima. Una de las primeras cuestiones que se abordan es el diseño de elementos ópticos secundarios para sistemas cuyo primario es una lente de Fresnel y que permiten, para una concentración fija, aumentar el ángulo de aceptancia y la tolerancia del sistema. Varios secundarios reflexivos y refractivos han sido diseñados y analizados mediante trazado de rayos. En particular, utilizando óptica anidólica y basándose en el diseño de una sola etapa conocido como ‘concentrador dieléctrico que funciona por reflexión total interna‘, se ha diseñado, fabricado y caracterizado un secundario con salida cuadrada que, usado junto con una lente de Fresnel, permite alcanzar simultáneamente una elevada eficiencia, concentración y aceptancia. Además, se ha propuesto y prototipado un método alternativo de fabricación para otro de los secundarios, denominado domo, consistente en el sobremoldeo de silicona sobre células solares. Una de las características que impregna todo el trabajo realizado en esta tesis es la aproximación holística en el diseño de módulos CPV, es decir, se ha prestado especial atención al diseño conjunto de la célula y la óptica para garantizar que el sistema total alcance la mayor eficiencia posible. En este sentido muchos sistemas ópticos desarrollados en esta tesis han sido diseñados, caracterizados y optimizados teniendo en cuenta que el ajuste de corriente entre las distintas subcélulas que comprenden la célula multiunión bajo el concentrador sea muy próximo a uno. La capa antirreflectante sobre la célula funciona, en cierto modo, como interfaz entre la óptica y la célula, por lo que se ha diseñado un método de optimización de capas antirreflectantes que considera no sólo el amplio rango de longitudes de onda para el que las células multiunión son sensibles sino también la distribución angular de intensidad sobre la célula creada por la óptica de concentración. Además, la cuestión de la falta de uniformidad también se ha abordado mediante la comparación de las distribuciones espectrales y espaciales de irradiancia que crean diferentes ópticas (simuladas mediante trazado de rayos y fotografiadas) y las pérdidas de eficiencia que experimentan las células iluminadas por dichas ópticas de concentración medidas experimentalmente. El efecto de la temperatura en la óptica de concentración también ha sido objeto de estudio de esta tesis. En particular, mediante simulaciones de elementos finitos se han dado los primeros pasos para el análisis de las deformaciones que sufren los dientes de las lentes de Fresnel híbridas (vidrio-silicona), así como el cambio de índice de refracción con la temperatura y la influencia de ambos efectos sobre el funcionamiento de los sistemas. Se ha implementado un modelo que tiene por objeto considerar las variaciones ambientales, principalmente temperatura y contenido espectral de la radiación directa, así como las sensibilidades térmica y espectral de los sistemas CPV, con el fin de maximizar la energía producida por un módulo de concentración a lo largo de un año en un emplazamiento determinado. Los capítulos 5 y 6 de este libro están dedicados al diseño, fabricación y caracterización de un nuevo concepto de módulo fotovoltaico denominado FluidReflex y basado en una única etapa reflexiva con dieléctrico fluido. En este nuevo concepto la presencia del fluido aporta algunas ventajas significativas como son: un aumento del producto concentración por aceptancia (CAP, en sus siglas en inglés) alcanzable al rodear la célula con un medio cuyo índice de refracción es mayor que uno, una mejora de la eficiencia óptica al disminuir las pérdidas por reflexión de Fresnel en varias interfaces, una mejora de la disipación térmica ya que el calor que se concentra junto a la célula se trasmite por convección natural y conducción en el fluido y un aislamiento eléctrico mejorado. Mediante la construcción y medida de varios prototipos de unidad elemental se ha demostrado que no existe ninguna razón fundamental que impida la implementación práctica del concepto teórico alcanzando una elevada eficiencia. Se ha realizado un análisis de fluidos candidatos probando la existencia de al menos dos de ellos que cumplen todos los requisitos (en particular el de estabilidad bajo condiciones de luz concentrada) para formar parte del sistema de concentración FluidReflex. Por ´ultimo, se han diseñado, fabricado y caracterizado varios prototipos preindustriales de módulos FluidReflex para lo cual ha sido necesario optimizar el proceso de fabricación de la óptica multicavidad a fin de mantener el buen comportamiento óptico obtenido en la fabricación de la unidad elemental. Los distintos prototipos han sido medidos, tanto en el laboratorio como bajo el sol real, analizando el ajuste de corriente de la célula iluminada por el concentrador FluidReflex bajo diferentes distribuciones espectrales de la radiación incidente así como el excelente comportamiento térmico del módulo. ABSTRACT A renewed interest in concentrating photovoltaic (CPV) systems has emerged in recent years encouraged by the development of high-efficiency multijunction solar cells based in IIIV semiconductors that have led to CPV module efficiencies which practically double that of flat panel PV and which reach 35% for record modules. This thesis is devoted to the design and experimental implementation of new concepts for obtaining CPV modules that not only achieve high efficiency under standard conditions but also have such a wide tolerance to assembly errors, tracking, temperature and spectral variations, that the energy generated by them throughout the year is maximized. One of the first addressed issues is the design of secondary optical elements whose primary optics is a Fresnel lens and which, for a fixed concentration, allow an increased acceptance angle and tolerance of the system. Several reflective and refractive secondaries have been designed and analyzed using ray tracing. In particular, using nonimaging optics and based on the single-stage design known as ‘dielectric totally internally reflecting concentrator’, a secondary with square output has been designed, fabricated and characterized. Used together with a Fresnel lens, the secondary can simultaneously achieve high efficiency, concentration and acceptance. Furthermore, an alternative method has been proposed and prototyped for the fabrication of the secondary named dome. The optics is manufactured by direct overmolding of silicone over the solar cells. One characteristic that permeates all the work done in this thesis is the holistic approach in the design of CPV modules, meaning that special attention has been paid to the joint design of the solar cell and the optics to ensure that the total system achieves the highest attainable efficiency. In this regard, many optical systems developed in the thesis have been designed, characterized and optimized considering that the current matching among the subcells within the multijunction solar cell beneath the optics must be close to one. Antireflective coating over the cell acts, somehow, as an interface between the optics and the cell. Consequently, a method has been designed to optimize antireflective coatings that takes into account not only the broad wavelength range that multijunction solar cells are sensitive to but also the angular intensity distribution created by the concentrating optics. In addition, the issue of non-uniformity has also been addressed by comparing the spectral and spatial distributions of irradiance created by different optics (simulated by ray tracing and photographed) and the efficiency losses experienced by cells illuminated by those concentrating optics experimentally determined. The effect of temperature on the concentrating optics has also been studied in this thesis. In particular, finite element simulations have been use to analyze the deformations experienced by the facets of hybrid (silicon-glass) Fresnel lenses, the change of refractive index with temperature and the influence of both effects on the system performance. A model has been implemented which take into consideration atmospheric variations, mainly temperature and spectral content of the direct normal irradiance, as well as thermal and spectral sensitivities of systems, with the aim of maximizing the energy harvested by a CPV module throughout the year in a particular location. Chapters 5 and 6 of this book are devoted to the design, fabrication, and characterization of a new concentrator concept named FluidReflex and based on a single-stage reflective optics with fluid dielectric. In this new concept, the presence of the fluid provides some significant advantages such as: an increased concentration acceptance angle product (CAP) achievable by surrounding the cell with a medium whose refractive index is greater than one, an improvement of the optical efficiency by reducing losses due to Fresnel reflection at several interfaces, an improvement in heat dissipation as the heat concentrated near the cell is transmitted by natural convection and conduction in the fluid, and an improved electrical insulation. By fabricating and characterizing several elementary-unit prototypes it was shown that there is no fundamental reason that prevents the practical implementation of this theoretical concept reaching high efficiency. Several fluid candidates were investigated proving the existence of at least to fluids that meet all the requirements (including the stability under concentrated light) to become part of the FluidReflex concentrator. Finally, several pre-industrial FluidReflex module prototypes have been designed and fabricated. An optimization process for the manufacturing of the multicavity optics was necessary to attain such an optics quality as the one achieved by the single unit. The module prototypes have been measured, both indoors and outdoors, analyzing the current matching of the solar cells beneath the concentrator for different spectral distribution of the incident irradiance. Additionally, the module showed an excellent thermal performance.

How can irrigated agriculture adapt to climate change? Insights from the Guadiana Basin in Spain

Climate change is already affecting many natural systems and human environments worldwide, like the semiarid Guadiana Basin in Spain. This paper illustrates a systematic analysis of climate change adaptation in the Guadiana irrigation farming region. The study applies a solution-oriented diagnostic framework structured along a series of sequential analytical steps. An initial stage integrates economic and hydrologic modeling to evaluate the effects of climate change on the agriculture and water sectors. Next, adaptation measures are identified and prioritized through a stakeholder-based multi-criteria analysis. Finally, a social network analysis identifies key actors and their relationships in climate change adaptation. The study shows that under a severe climate change scenario, water availability could be substantially decreased and drought occurrence will augment. In consequence, farmers will adapt their crops to a lesser amount of water and income gains will diminish, particularly for smallholder farms. Among the various adaptation measures considered, those related to private farming (new crop varieties and modern irrigation technologies) are ranked highest, whereas public-funded hard measures (reservoirs) are lowest and public soft measures (insurance) are ranked middle. In addition, stakeholders highlighted that the most relevant criteria for selecting adaptation plans are environmental protection, financial feasibility and employment creation. Nonetheless, the social network analysis evidenced the need to strengthen the links among the different stakeholder groups to facilitate the implementation of adaptation processes. In sum, the diagnostic framework applied in this research can be considered a valuable tool for guiding and supporting decision making in climate change adaptation and communicating scientific results.

Implementación de un entorno de mantenimiento centralizado para el diagnóstico y aislamiento de fallos en plataformas de sistemas modulares

En la actualidad gran parte de las industrias utilizan o desarrollan plataformas, las cuales integran un número cada vez más elevado de sistemas complejos. El mantenimiento centralizado permite optimizar el mantenimiento de estas plataformas, por medio de la integración de un sistema encargado de gestionar el mantenimiento de todos los sistemas de la plataforma. Este Trabajo Fin de Máster (TFM) desarrolla el concepto de mantenimiento centralizado para sistemas complejos, aplicable a plataformas formadas por sistemas modulares. Está basado en la creciente demanda de las diferentes industrias en las que se utilizan este tipo de plataformas, como por ejemplo la industria aeronáutica, del ferrocarril y del automóvil. Para ello este TFM analiza el Estado del Arte de los sistemas de mantenimiento centralizados en diferentes industrias, además desarrolla los diferentes tipos de arquitecturas de sistemas, las técnicas de mantenimiento aplicables, así como los sistemas y técnicas de mantenimiento basados en funciones de monitorización y auto diagnóstico denominadas Built-In-Test Equipment (BITE). Adicionalmente, este TFM incluye el desarrollo e implementación de un modelo de un Entorno de Mantenimiento Centralizado en LabVIEW. Este entorno está formado por el modelo de un Sistema Patrón, así como el modelo del Sistema de Mantenimiento Centralizado y la interfaces entre ellos. El modelo del Sistema de Mantenimiento Centralizado integra diferentes funciones para el diagnóstico y aislamiento de los fallos. Así mismo, incluye una función para el análisis estadístico de los datos de fallos almacenados por el propio sistema, con el objetivo de proporcionar capacidades de mantenimiento predictivo a los sistemas del entorno. Para la implementación del modelo del Entorno de Mantenimiento Centralizado se han utilizado recursos de comunicaciones vía TCP/IP, modelización y almacenamiento de datos en ficheros XML y generación automática de informes en HTML. ABSTRACT. Currently several industries are developing or are making use of multi system platforms. These platforms are composed by many complex systems. The centralized maintenance allows the maintenance optimization, integrating a maintenance management system. This system is in charge of managing the maintenance dialog with the different and multiple platforms. This Master Final Project (TFM) develops the centralized maintenance concept for platforms integrated by modular and complex systems. This TFM is based on the demand of the industry that uses or develops multi system platforms, as aeronautic, railway, and automotive industries. In this way, this TFM covers and analyzes several aspects of the centralized maintenance systems like the State of the Art, for several industries. Besides this work develops different systems architecture types, maintenance techniques, and techniques and systems based on Built-in-test Equipment functions. Additionally, this TFM includes a LabVIEW Centralized System Environment model. This model is composed by a Standard System, the Centralized Maintenance System and the corresponding interfaces. Several diagnostic and fault isolation functions are integrated on the Centralized Maintenance Systems, as well a statistic analysis function, that provides with predictive maintenance capacity, based on the failure data stored by the system. Among others, the following resources have been used for the Centralized System Environment model development: TCP/IP communications, XML file data modelization and storing, and also automatic HTML reports generation.

La unidad de lo dual : tradición y modernidad en la obra de Tadao Ando y Toyo Ito

La referencia a la tradición como una fuerza capaz de aportar unidad, al abarcar tanto la continuidad como los cambios en las expresiones al margen de la época o las técnicas empleadas, ha sido siempre un componente muy importante de las manifestaciones artísticas de Japón y es la sutil ligazón que las conecta desde el pasado hasta la actualidad. Se entiende aquí que tradición no equivale simplemente a preservación, sino que se trata de una transmisión con una vertiente dual, pues permite una constante evolución sin que se altere su esencia básica. Es de esta forma que la cultura japonesa de la era Edo (1600-1868), con su alto grado de innovación, riqueza y sofisticación, pero además como epílogo histórico previo a la Restauración Meiji de 1868, ha sido la referencia clave en lo relativo a esa mirada a la tradición nipona para el desarrollo de esta tesis. A partir de la segunda mitad del siglo XIX, todas estas características tan genuinas del período Edo quedaron en suspenso y, desde entonces, Japón ha seguido la vía de la modernización (que en muchos aspectos ha sido también la de la occidentalización). Los entrelazamientos de otras dualidades provocados en Japón por los ataques nucleares de 1945 condujeron a una inevitable fusión de aquel mundo físico con el mundo metafísico, de aquella terrible presencia con un tremendo sentimiento de ausencia y, en definitiva, de Oriente con Occidente. El consiguiente impacto sobre la cultura de la nación tuvo una especial repercusión en el ámbito arquitectónico. En este sentido, el pensamiento francés ha desempeñado un papel fundamental en el replanteamiento radical de muchos supuestos esenciales, de muchos conceptos y valores de la cultura occidental, incluyendo los procedentes de la Ilustración, en este mundo contemporáneo que es cada vez más complejo y plural. Éstos y otros hechos otorgan a la cultura japonesa tradicional una cualidad multidimensional (frente a la marcada bidimensionalidad que suele caracterizar a las culturas occidentales) que, tal y como esta tesis doctoral pretende poner de manifiesto, podría revelarse como una «síntesis de contradicciones» en la obra de los arquitectos japoneses Tadao Ando (Osaka, 1941-) y Toyo Ito (Keijo, actual Seúl, 1941-). En el pensamiento oriental una dualidad es entendida como la complementariedad entre dos polos, sólo en apariencia opuestos, que integra dos vertientes de un único concepto. Al igual que la idea de «parejas» budista, concebida según esta doctrina como una unidad entre dos extremos inevitablemente interrelacionados, el objetivo principal sería el de poner de manifiesto cómo la obra de ambos arquitectos trata de resolver los mismos conflictos partiendo de puntos de vista polarizados. ABSTRACT The reference to tradition as a force for unity, encompassing both continuity and changes in expressions regardless of the time or techniques used, has always been a very important component of the artistic manifestations of Japan and it is the subtle link that connects them from the past to the present. It is understood here that tradition does not mean simply preservation, but it is a transmission with a dual aspect, because it allows a constant evolution without altering its basic essence. It is thus that the Japanese culture of the Edo era (1600-1868), with its high degree of innovation, wealth and sophistication, but also as a historical epilogue prior to the Meiji Restoration of 1868 has been the key reference concerning that look to the Japanese tradition for the development of this thesis. From the second half of the 19th century, all these as genuine features of the Edo period remained at a standstill and, since then, Japan has followed the path of modernization (which has also been that of Westernization in many ways). The interlacements of other dualities caused in Japan by the 1945 nuclear attacks led to an inevitable fusion of the physical with the metaphysical world, of that terrible presence with a tremendous sense of absence and, eventually, of East with West. The resulting impact on the culture of the nation had a special repercussion on the architectural field. In this sense, the French thought has played a key role in the radical rethinking of many core assumptions, many concepts and values of Western thought, including those from the Age of Enlightenment, in this contemporary world that is increasingly complex and plural. These and other facts give the traditional Japanese culture a multidimensional quality (opposed to the marked two-dimensionality that usually characterizes Western cultures). As this thesis aims to highlight, this could prove to be a «synthesis of contradictions» in the work of Japanese architects Tadao Ando (Osaka, 1941-) and Toyo Ito (Keijo, current Seoul, 1941-). In the Eastern thought a duality is understood as the complementarity between two poles, only apparently opposite, which integrates two aspects of a single concept. Like the Buddhist notion of «couples» (conceived according to this doctrine as a unity between two inevitably interlinked extremes) the main objective would be to show how the work of both architects tries to resolve the same conflicts starting with polarized viewpoints.

Patterns of brain angiogenesis after vascular endothelial growth factor administration in vitro and in vivo

Vascular endothelial growth factor (VEGF) is a secreted endothelial cell mitogen that has been shown to induce vasculogenesis and angiogenesis in many organ systems and tumors. Considering the importance of VEGF to embryonic vascularization and survival, the effects of administered VEGF on developing or adult cerebrovasculature are unknown: can VEGF alter brain angiogenesis or mature cerebrovascular patterns? To examine these questions we exposed fetal, newborn, and adult rat cortical slice explants to graduated doses of recombinant VEGF. The effects of another known angiogenic factor, basic fibroblast growth factor (bFGF), were evaluated in a comparable manner. In addition, we infused VEGF via minipump into the adult cortex. Significant angiogenic effects were found in all VEGF experiments in a dose-responsive manner that were abolished by the addition of VEGF neutralizing antibody. Fetal and newborn explants had a highly complex network of branched vessels that immunoexpressed the flt-1 VEGF receptor, and flk-1 VEGF receptor expression was determined by reverse transcription–PCR. Adult explants had enlarged, dilated vessels that appeared to be an expansion of the existing network. All bFGF-treated explants had substantially fewer vascular profiles. VEGF infusions produced both a remarkable localized neovascularization and, unexpectedly, the expression of flt-1 on reactive astrocytes but not on endothelial cells. The preponderance of neovascularization in vitro and in vivo, however, lacked the blood–brain barrier (BBB) phenotype marker, GLUT-1, suggesting that in brain the angiogenic role of VEGF may differ from a potential BBB functional role, i.e., transport and permeability. VEGF may serve an important capacity in neovascularization or BBB alterations after brain injury.

Reduced fertility in mice deficient for the POU protein sperm-1

Members of the POU-homeodomain gene family encode transcriptional regulatory molecules that play important roles in terminal differentiation of many organ systems. Sperm-1 (Sprm-1) is a POU domain factor that is exclusively expressed in the differentiating male germ cell. We show here that the Sprm-1 protein is expressed in the haploid spermatid and that 129/Sv Sprm-1(−/−) mice are subfertile when compared with wild-type or heterozygous littermates yet exhibit normal testicular morphology and produce normal numbers of mobile spermatozoa. Our data suggest that the Sprm-1 protein plays a discrete regulatory function in the haploid spermatid, which is required for the optimal function, but not the terminal differentiation, of the male germ cell.

The Involvement of Hydrogen Peroxide in the Differentiation of Secondary Walls in Cotton Fibers1

H2O2 is a widespread molecule in many biological systems. It is created enzymatically in living cells during various oxidation reactions and by leakage of electrons from the electron transport chains. Depending on the concentration H2O2 can induce cell protective responses, programmed cell death, or necrosis. Here we provide evidence that H2O2 may function as a developmental signal in the differentiation of secondary walls in cotton (Gossypium hirsutum) fibers. Three lines of evidence support this conclusion: (a) the period of H2O2 generation coincided with the onset of secondary wall deposition, (b) inhibition of H2O2 production or scavenging the available H2O2 from the system prevented the wall differentiation process, and (c) exogenous addition of H2O2 prematurely promoted secondary wall formation in young fibers. Furthermore, we provide support for the concept that H2O2 generation could be mediated by the expression of the small GTPase Rac, the accumulation of which was shown previously to be strongly induced during the onset of secondary wall differentiation. In support of Rac's role in the activation of NADPH oxidase and the generation of reactive oxygen species, we transformed soybean (Glycine max) and Arabidopsis cells with mutated Rac genes. Transformation with a dominantly activated cotton Rac13 gene resulted in constitutively higher levels of H2O2, whereas transformation with the antisense and especially with dominant-negative Rac constructs decreased the levels of H2O2.

Historical overview: Searching for replication help in all of the rec places

For several decades, research into the mechanisms of genetic recombination proceeded without a complete understanding of its cellular function or its place in DNA metabolism. Many lines of research recently have coalesced to reveal a thorough integration of most aspects of DNA metabolism, including recombination. In bacteria, the primary function of homologous genetic recombination is the repair of stalled or collapsed replication forks. Recombinational DNA repair of replication forks is a surprisingly common process, even under normal growth conditions. The new results feature multiple pathways for repair and the involvement of many enzymatic systems. The long-recognized integration of replication and recombination in the DNA metabolism of bacteriophage T4 has moved into the spotlight with its clear mechanistic precedents. In eukaryotes, a similar integration of replication and recombination is seen in meiotic recombination as well as in the repair of replication forks and double-strand breaks generated by environmental abuse. Basic mechanisms for replication fork repair can now inform continued research into other aspects of recombination. This overview attempts to trace the history of the search for recombination function in bacteria and their bacteriophages, as well as some of the parallel paths taken in eukaryotic recombination research.