(Table S1) Age determination of ODP Site 202-1240

Interannual-decadal variability in the equatorial Pacific El Niño-Southern Oscillation (ENSO) induces climate changes at global scale, but its potential influence during past global climate change is not yet well constrained. New high-resolution eastern equatorial Pacific proxy records of thermocline conditions present new evidence of strong orbital control in ENSO-like variability over the last 275,000 years. Recurrent intervals of saltier thermocline waters are associated with the dominance of La Niña-like conditions during glacial terminations, coinciding with periods of low precession and high obliquity. The parallel dominance of d13C-depleted waters supports the advection of Antarctic origin waters toward the tropical thermocline. This "oceanic tunneling" is proposed to have reinforced orbitally induced changes in ENSO-like variability, composing a complex high- and low-latitude feedback during glacial terminations.

Reliability analysis based on non-dimensional parameters

A reliability analysis method is proposed that starts with the identification of all variables involved. These are divided in three groups: (a) variables fixed by codes, as loads and strength project values, and their corresponding partial safety coefficients, (b) geometric variables defining the dimension of the main elements involved, (c) the cost variables, including the possible damages caused by failure, (d) the random variables as loads, strength, etc., and (e)the variables defining the statistical model, as the family of distribution and its corresponding parameters. Once the variables are known, the II-theorem is used to obtain a minimum equivalent set of non-dimensional variables, which is used to define the limit states. This allows a reduction in the number of variables involved and a better understanding of their coupling effects. Two minimum cost criteria are used for selecting the project dimensions. One is based on a bounded-probability of failure, and the other on a total cost, including the damages of the possible failure. Finally, the method is illustrated by means of an application.

Biblia. A.T. Poliglota

Copia digital: Biblioteca valenciana, 2010

Losa ortótropa circular

Se presenta aquí un análisis elástico de la losa curva, apoyada en dos bordes radiales y con condiciones de sustentación muy generales en sus bordes curvos, y que pueden englobarse en la condición de existencia de vigas. La construcción moderna de autopistas con puentes que deben adaptarse a las necesidades de su trazado ha traido la aparición de puentes irregulares en planta y alzado, que exigen para su cálculo métodos numéricos.Este tipo estructural se caracteriza por su planta circular, y su análisis, en general, no puede ser asimilado al puente rectangular cuyo estudio analítico es más conocido.

Juan Bautista Lázaro y la restauración monumental: su intervención en la Catedral de León (1892-1909)

La catedral de León, debido al estado de ruina que presentaba a mediados del siglo XIX, se vio sometida a partir de entonces a una serie de intervenciones de conservación, restauración y reconstrucción que la transforma-ron significativamente. A pesar de encontrarnos con gran cantidad de documentación escrita sobre este monumento y de existir varios estudios sobre los arquitectos restauradores que intervinieron en este a finales del siglo XIX, resulta sorprendente que todavía existan períodos de este lapso de tiempo en el que su análisis y profundización haya sido menor. Este es el caso del período de Juan Bautista Lázaro como arquitecto director de las obras de la catedral leonesa, existiendo únicamente sobre toda su obra un estudio general que fue realizado por el director de este trabajo de investigación, por lo que nos llevó a considerar que era oportuno profundizar sobre la figura y obra de uno de los arquitectos más importante de la restauración en España de este período, no solo por su obra en sí, sino también por sus pos-turas significativas respecto a la intervención en el patrimonio arquitectónico: su respeto por los añadidos históricos, su preferencia por no aislar los monumentos, sus interés por los sistemas constructivos y su deseo de recuperar los oficios tradicionales que estaban completamente perdidos en la España decimonónica. El objetivo principal de la tesis es, por tanto, el análisis descriptivo y arquitectónico de los proyectos e intervenciones que Lázaro desarrolló y ejecutó para la catedral de Santa María de Regla de León, para deducir los principios e ideas que guiaron su quehacer en este templo, y poder, tras estudiar sus diversas publicaciones escritas y los proyectos e intervenciones de restauración acometidas en otros edificios de carácter monumental, llegar a establecer sus criterios de intervención en el patrimonio histórico y artístico. De acuerdo con esto, la tesis se estructura en tres partes: una primera parte en la que se contempla el pensamiento arquitectónico de Lázaro en su intervención en el patrimonio histórico; una segunda, en la que se abordan directamente los proyectos e intervenciones de Lázaro en la pulchra leonina, previa aproximación del citado arquitecto al proceso de restauración que se acometía en dicho templo; y una tercera, en la que se realiza el estudio de las principales intervenciones de restauración que ejecutó en otros edificios del patrimonio arquitectónico español. El presente trabajo de investigación se ha servido de la documentación escrita, gráfica, planimétrica y fotográfica que sobre los temas tratados existe desperdigada en diversos archivos dependientes de distintos organismos oficiales civiles y eclesiásticos. Además, el hecho de haber podido acceder a los trabajos de conservación y restauración que en estos momentos se están llevando a cabo en las zonas en las que intervino Lázaro (vidrieras, rejas, puertas, fábricas, cubiertas, etc.), y el poder intercambiar opiniones y criterios con la persona que actualmente es responsable de las obras de la catedral de León, ha facilitado y complementado el desarrollo de la presente tesis al haber podido contrastar y tomar datos directamente en el monumento objeto de estudio. También se ha llevado a cabo la consulta de las distintas revistas de arquitectura publicadas en aquellos años y de los múltiples libros que versaban sobre los edificios objeto de este trabajo o que guardaban relación con ellos. Asimismo hemos logrado conocer el testimonio de algunos de los herederos de Lázaro y de varios de los descendientes de los operarios que trabajaron bajo sus órdenes. Como conclusiones generales, la tesis define por primera vez los criterios generales que guiaron su quehacer profesional en el patrimonio. Además, en este trabajo se analizan pormenorizadamente los proyectos y actuaciones de Lázaro en la catedral de León, abordándose también en profundidad el trabajo del mencionado arquitecto en el ámbito de la restauración arquitectónica. Para lograr este objetivo, esta tesis no se ha limitado únicamente a analizar la información existente en los proyectos y en los in-formes de supervisión de los mismos, como tradicionalmente se había hecho, sino que también se ha tratado de verificar si los datos contenidos en los diferentes documentos de un mismo proyecto y en los borradores de los mismos tenían relación y coherencia entre sí. Además, se ha procurado realizar el análisis comparativo de la realidad construida con el contenido de los proyectos, liquidaciones y documentos de la fase de ejecución de las obras. Este análisis comparativo no había sido realizado hasta la fecha, siendo este, por tanto, una de las aportaciones del trabajo. Por último, la tesis abre tres vías de investigación futuras (que ya se han tratado y avanzado en parte, pero que escapan a los límites de este trabajo). Estas se refieren al estudio de la evolución de la representación gráfica de los planos de la catedral leonesa catalogados en este trabajo, de la actividad pública de Lázaro y su preocupación por la defensa del patrimonio como diputado en las Cortes, arquitecto municipal de Ávila y arquitecto diocesano de Ávila y Toledo, y de cómo sus actuaciones de restauración en el patrimonio arquitectónico influyeron en los proyectos de obra nueva que construyó. ABSTRACT Due to the state of ruin in mid-nineteenth century, the Cathedral of Santa Maria de Regla of León was subjected to a series of interventions on conservation, restoration and reconstruction that transformed it significantly. There have been several studies on the architects who took part in the restoration during the mentioned century and despite abundant documentation and research on this monument, it is surprising to note the lack of deep analysis in some of the periods. In particular, the interventions accomplished by Juan Bautista Lázaro, as chief architect of the works of the Cathedral of León, have not been documented and analysed in adequate depth, despite the outstanding recognition of his work nationally and internationally. Furthermore, up to date, only the director of this research had conducted a general research of all his architectural work. For these reasons, we felt it was appropriate to elaborate on the life and work of one of the most important architects of the restoration in Spain during that period, not only for his work itself, but also for his significant contribution to the debate on architectural interventions on heritage. He is notable for his respect to historical additions, his preference for not isolating the monuments, his interest in building systems and his continuous desire to re-cover the traditional crafts that were completely lost in the nineteenth century in Spain. The main aim of this thesis is therefore the descriptive and architectural analysis of Lázaro’s projects and interventions developed and executed for the Cathedral of León. The thesis identifies the principles and ideas that guided his work in this temple and establish the criteria for intervention in the historical and artistic heritage architecture he applied after studying its various print publications, projects and restoration works undertaken in other buildings. Accordingly, the thesis is structured in three parts: the first part where it deals Lázaro’s architectural thinking in his interventions on heritage constructions; the second one, in which analyses the projects and interventions carried out by Lazaro in the “pulchra leonina”, but this analysis is preceded by the description of Lázaro’s relationship with the Cathedral of León before taking charge of its restoration in 1892; and the third and final section, in which the study of major restoration interventions implemented by Lázaro in other buildings of Spanish architectural heritage is made. This research has used available documentation (in written or graphic form, plans or photographs) scattered in a diverse range of archives de-pendent on various civil and ecclesiastical institutions. Moreover, we could access the conservation and restoration works, currently being carried out in areas where Lázaro intervened (stained glass windows, forged iron en-closures, gates, doors, masonry, covers, etc.). It has been possible to ex-change views and opinions with the person currently in charge of the referred restoration works which has facilitated and complemented the development of this thesis. It further, it has allowed contrasting and obtaining data directly from the monument under study. Consultation of various architectural journals published in those years has also been taken into account, as well as a diversity of books and articles which concerned the buildings assessed in this work, or related to them. Also, although not with the results expected, it has been obtained the testimony of some of Lázaro’s descendants as well as descendants of the workers who operated under him. As a general conclusion, the thesis defines the general criteria that guided his professional work in the heritage for the first time. Furthermore, Juan Bautista Lázaro’s projects and interventions in the Cathedral of León are analysed in detail. Also, it has been studying in detail the Lazaro’s work in the architectural heritage. To achieve this goal, the thesis has studied not only the information from the official projects and technical reports of them, but also it has been tried to verify if the information contained in the different documents of the same project and in the drafts were related and consistent with each other. In addition, it has been attempted to per-form a comparative analysis of the execution of Lázaro’s projects and the entire projected content. This comparative study had not been done to date and this will be, therefore, one of the main contributions of this re-search. Finally, this thesis opens up three lines of investigation (that have already been discussed and partially advanced, but which fall beyond the scope of this research). These refer to the study of the evolution of the graphical representation of the plans of Leon Cathedral catalogued in this thesis, public activity of Lazaro and his concern for the defence of heritage as deputy in Parliament, municipal architect of Avila, and as diocesan architect Ávila and Toledo, and even more how its restoration actions in architectural heritage influenced his projects of new construction.

E.D.A.R. Boadilla del Monte

El objeto del presente proyecto es definir y valorar las obras e instalaciones necesarias para la nueva estación depuradora de aguas residuales del municipio de Boadilla del Monte. Se trata de un municipio con fuerte expansión urbanística y, por tanto, con un importante crecimiento poblacional, lo que justifica la necesidad de construcción de una nueva estación de depuración para las aguas residuales. El proyecto tratará las alternativas de las instalaciones necesarias, valorándolas y llegando a la elección óptima para tratar las aguas residuales del conjunto del municipio, de tal manera que alcancen objetivos de calidad de las aguas necesarios. En el presente documento se analizarán con detalle todos los parámetros necesarios para la definición de la E.D.A.R.

A MULHER ALÉM DO BEM E DO MAL: Malévola e a representação cinematográfica do feminino integrado

Estudo sobre as construções simbólicas e identitárias da mulher presentes na narrativa e na estrutura das personagens femininas do filme Malévola (2014) – produção dos estúdios Disney (EUA). A narrativa é inspirada no conto de fadas “A Bela Adormecida do Bosque” e distingue-se pela perspectiva feminina, modificando as possibilidades de interpretação, além de possibilitar a quebra do paradigma dicotômico relacionado ao Bem e ao Mal. A pesquisa tem por objetivo estudar a evolução das construções imaginárias da mulher no cinema e traçar paralelos entre as características arquetípicas das personagens de Malévola em relação à identidade da mulher na contemporaneidade. Para tal, será tomado como referencial teórico os estudos do imaginário social, com as obras de Gilbert Durand, Edgar Morin e, em especial, Michel Maffesoli; conceitos da psicanálise a partir dos trabalhos de C.G. Jung, Erich Neumann, Marie-Louise Von Franz e Clarissa Pinkola Estés; as teorias de Stuart Hall, Laura Mulvey e Gilles Lipovetsky relacionadas aos estudos culturais com ênfase em gênero; e também o ecofeminismo através dos trabalhos de autoras como Vandana Shiva e Maria Mies. Nosso referencial teórico-metodológico é a Hermenêutica de Profundidade (HP) visando à interpretação da estrutura simbólica de nosso objeto. Resultam desta pesquisa a verificação de um processo de saturação de padrões identitários e simbólicos provindos da modernidade e a evolução de novas dinâmicas nas narrativas presentes nas mídias e na comunicação

Effectiveness of initiating extrafine-particle versus fine-particle inhaled corticosteroids as asthma therapy in the Netherlands

Acknowledgements Gokul Gopalan (a Senior Global Medical Director [Respiratory], at Teva Pharmaceuticals, Frazer, PA, US, at the time of this study), assisted with study design. Funding Funds to acquire the dataset from the Pharmo Institute for Drug Outcomes Research (Utrecht, the Netherlands) were provided by RiRL. The study received institutional support from Teva Pharmaceuticals Europe B.V. Gokul Gopalan, a Senior Global Medical Director (Respiratory), at Teva Pharmaceuticals, Frazer, PA, US, at the time of this study, assisted with study design, but neither Teva Pharmaceuticals Europe B.V. nor Teva Pharmaceuticals, Frazer, PA, US, contributed, either in part or in whole, to the collection, analysis, or interpretation of study data, manuscript writing, or the decision to submit the manuscript for publication. Erratum The original version of this article unfortunately contained errors that have since been corrected. The word “pharmo” has been fully capitalised to “PHARMO” throughout the article. The reference to Table 2 in the first and second sentence under the Outcomes heading has been replaced with Fig. 3. Under the Abbreviations heading ‘extrafine-particle’ was repeated, this has been corrected to ‘EF-HFA-BDP [Qvar®]: extrafine-particle hydrofluoroalkane beclomethasone dipropionate’. The competing interests of Nicolas Roche and Theresa Guibert have been amended. Academic affiliations for Dirkje S. Postma (2), Richard J. Martin (3), Ron M.C. Herrings (4), Jetty Overbeek (4), and Nicolas Roche (7) have been corrected. Figure 3 in the online and pdf version did not match, this been amended

Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes

Analysis of perforin-deficient mice has identified the cytolytic pathway and perforin as the preeminent effector molecule in T cell-mediated control of virus infections. In this paper, we show that mice lacking both granzyme A (gzmA) and granzyme B (gzmB), which are, beside perforin, key constituents of cytolytic vesicles, are as incapable as are perforin-deficient mice of controlling primary infections by the natural mouse pathogen ectromelia, a poxvirus. Death of gzmA×gzmB double knockout mice occurred in a dose-dependent manner, despite the expression of functionally active perforin and the absence of an intrinsic defect to generate splenic cytolytic T cells. These results establish that both gzmA and gzmB are indispensable effector molecules acting in concert with perforin in granule exocytosis-mediated host defense against natural viral pathogens.

Emergence of a highly pathogenic simian/human immunodeficiency virus in a rhesus macaque treated with anti-CD8 mAb during a primary infection with a nonpathogenic virus

Although simian/human immunodeficiency virus (SHIV) strain DH12 replicates to high titers and causes immunodeficiency in pig-tailed macaques, virus loads measured in SHIVDH12-infected rhesus monkeys are consistently 100-fold lower and none of 22 inoculated animals have developed disease. We previously reported that the administration of anti-human CD8 mAb to rhesus macaques at the time of primary SHIVDH12 infection resulted in marked elevations of virus loads. One of the treated animals experienced rapid and profound depletions of circulating CD4+ T lymphocytes. Although the CD4+ T cell number partially recovered, this monkey subsequently suffered significant weight loss and was euthanized. A tissue culture virus stock derived from this animal, designated SHIVDH12R, induced marked and rapid CD4+ cell loss after i.v. inoculation of rhesus monkeys. Retrospective analyses of clinical specimens, collected during the emergence of SHIVDH12R indicated: (i) the input cloned SHIV remained the predominant virus during the first 5–7 months of infection; (ii) variants bearing only a few of the SHIVDH12R consensus changes first appeared 7 months after the administration of anti-CD8 mAb; (iii) high titers of neutralizing antibody directed against the input SHIV were detected by week 10 and persisted throughout the infection; and (iv) no neutralizing antibody against SHIVDH12R ever developed.

Transgenic tobacco plants with reduced capability to detoxify reactive oxygen intermediates are hyperresponsive to pathogen infection

Reactive oxygen intermediates (ROI) play a critical role in the defense of plants against invading pathogens. Produced during the “oxidative burst,” they are thought to activate programmed cell death (PCD) and induce antimicrobial defenses such as pathogenesis-related proteins. It was shown recently that during the interaction of plants with pathogens, the expression of ROI-detoxifying enzymes such as ascorbate peroxidase (APX) and catalase (CAT) is suppressed. It was suggested that this suppression, occurring upon pathogen recognition and coinciding with an enhanced rate of ROI production, plays a key role in elevating cellular ROI levels, thereby potentiating the induction of PCD and other defenses. To examine the relationship between the suppression of antioxidative mechanisms and the induction of PCD and other defenses during pathogen attack, we studied the interaction between transgenic antisense tobacco plants with reduced APX or CAT and a bacterial pathogen that triggers the hypersensitive response. Transgenic plants with reduced capability to detoxify ROI (i.e., antisense APX or CAT) were found to be hyperresponsive to pathogen attack. They activated PCD in response to low amounts of pathogens that did not trigger the activation of PCD in control plants. Our findings support the hypothesis that suppression of ROI-scavenging enzymes during the hypersensitive response plays an important role in enhancing pathogen-induced PCD.

Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): Characterization of connective tissue growth factor as a member of the IGFBP superfamily

The insulin-like growth factor (IGF) binding proteins (IGFBPs) modulate the actions of the insulin-like growth factors in endocrine, paracrine, and autocrine settings. Additionally, some IGFBPs appear to exhibit biological effects that are IGF independent. The six high-affinity IGFBPs that have been characterized to date exhibit 40–60% amino acid sequence identity overall, with the most conserved sequences in their NH2 and COOH termini. We have recently demonstrated that the product of the mac25/IGFBP-7 gene, which shows significant conservation in the NH2 terminus, including an “IGFBP motif” (GCGCCXXC), exhibits low-affinity IGF binding. The closely related mammalian genes connective tissue growth factor (CTGF) gene, nov, and cyr61 encode secreted proteins that also contain the conserved sequences and IGFBP motifs in their NH2 termini. To ascertain if these genes, along with mac25/IGFBP-7, encode a family of low-affinity IGFBPs, we assessed the IGF binding characteristics of recombinant human CTGF (rhCTGF). The ability of baculovirus-synthesized rhCTGF to bind IGFs was demonstrated by Western ligand blotting, affinity cross-linking, and competitive affinity binding assays using 125I-labeled IGF-I or IGF-II and unlabeled IGFs. CTGF, like mac25/IGFBP-7, specifically binds IGFs, although with relatively low affinity. On the basis of these data, we propose that CTGF represents another member of the IGFBP family (IGFBP-8) and that the CTGF gene, mac25/IGFBP-7, nov, and cyr61 are members of a family of low-affinity IGFBP genes. These genes, along with those encoding the high-affinity IGFBPs 1–6, together constitute an IGFBP superfamily whose products function in IGF-dependent or IGF-independent modes to regulate normal and neoplastic cell growth.