CONTRASTING EFFECTS OF AN MDM2 FUNCTIONAL POLYMORPHISM ON TUMOR PHENOTYPES

Cancer predisposition by the cooperation of genetic variants, such as single nucleotide polymorphisms (SNPs), may be of much greater significance to public health than previously appreciated. Functional polymorphisms are genetic variants that alter gene function. Meta-analyses associate many functional polymorphisms with cancer risk. The MDM2 SNP309G allele is a cancer-associated functional polymorphism positioned in the MDM2 P2 promoter that enhances transcription factor SP1 binding, resulting in elevated levels of MDM2 concomitant with decreased p53 tumor-suppressor activity. Mdm2SNP309G/G mice are more prone to spontaneous tumor formation than Mdm2SNP309T/T mice, providing direct evidence for the impact of this SNP on tumor development. We examined the impact of SNP309 on cancer risk in response to environmental factors by treating SNP309 mice with ionizing radiation, UVB, or Benzo(a)pyrene. The results show that SNP309G cooperates with ionizing radiation to exacerbate tumor development. Contrastingly, ultraviolet B light or Benzo(a)pyrene exposure of skin indicates that SNP309G allele protects against squamous cell carcinoma susceptibility. These contradicting differences led us to interrogate the mechanism by which Mdm2 SNP309 regulates tumor susceptibility in a tissue-specific manner. The assessment of potential transcriptional regulators in ENCODE ChIP-seq database identified transcriptional repressor E2F6 as a possible negative regulator of MDM2 expression. Our data show that E2F6 protein is expressed at higher levels in skin keratinocytes of SNP309 mice as compared to lymphatic tissues. Furthermore, E2F6 binds and suppresses Mdm2 expression in cells harboring the SNP309G allele but not the SNP309T allele. Thus, the Mdm2 SNP309G allele exhibits tissue-specific regulation and differentially impacts cancer risk

Aspect-Oriented Techniques for Web Services: a Model-Driven Approach

Web Service technologies offer a successful way for interoperability among applications, but in order to tackle the entire web service life cycle, it is necessary to face how to model systems based on service functionality and also how to add extra-functional properties to modelled services. In this regard, we propose first of all a versatile and simple UML profile based on the Service Component Architecture specification for modelling services, in order to provide a model environment in which to add extra-functional properties. Secondly, a new UML profile is proposed to model and reuse the said extra-functional properties in service models. The implemented models based on these profiles will be independent from a final implementation language or platform, thus it is necessary to specify a particular type of model to convert the independent one into in a subsequent step. In order to meet this requirement an object, an aspect and a policy based models are proposed as the intermediate step between the independent model and the final code. We acknowledge that there are tools available which convert Java models into web services\u27 Java code, and it is not our aim to build a tool to fulfil this requirement. Regarding extra-functional properties, aspect-oriented techniques allow them to be easily modularized and reused; in this respect, properties are implemented as aspects in a totally transparent way and avoid the need to modify service code in an intrusive manner on adding extra-functional properties, improving our system maintenance. Furthermore, this way traceability between the model and the code is perfectly maintained in both directions. This work has been developed thanks to the support of CICYT under contract TIN2005-09405-C02-02

Towards UML Modelling Extra-Functional Properties in Web Services and their Clients

Web Services provide our systems with a platform independent and loosely coupled implementation environment, being time to face how the named systems can be modelled. Service Component Architecture (SCA) allows us to define services independently of the final implementation technology; however, it does not integrate the remaining development stages. Model Driven Architecture provides a method to face all stages in development from the platform independent model to final code, although it is not specific to service technologies. Regarding web service extra-functional properties, WS-Policy establishes how to describe them in a loosely coupled manner; however the loosely coupled environment is not always maintained when modelling or implementing these properties, which can be solved by using aspect-oriented techniques. In this paper, we propose to use a model driven approach for extra-functional properties in SCA service based models, where generated code will consist of the policy description and an aspect-oriented implementation

Interculturalidad, saberes campesinos y educación.

La observación in situ y el análisis de las formas de producción y de reproducción del conocimiento nos han permitido mostrar la existencia de un sistema campesino de conocimientos productivos y tecnológicos, cuyas maneras de acumulación y ruta técnica difieren de las del sistema tecnoproductivo moderno. Sin embargo, la existencia de un paradigma tecnoproductivo campesino y uno moderno, no implica el aislamiento o la autarquía del primero, por el contrario, en las elecciones técnicas cotidianas del campesino se produce un acoplamiento entre los saberes técnicos modernos y los tradicionales. La investigación indica que en los contenidos técnicos enseñados en las escuelas agropecuarias, predomina un modelo productivo orientado hacia la mediana y gran empresa agropecuaria. Este modelo educativo subordina los saberes que tradicionalmente han permitido la resolución de problemas en las producciones locales. Sin embargo, en los diferentes tipos de prácticas escolares y ante la urgencia de dar respuestas en los procesos productivos reales, se pierde la predominancia del modelo tecnológico dominante y se recupera la experiencia de los productores locales

Las visitas pastorales de los obispos Ramón Torrijos Gómez y Félix Soto Mancera al Seminario Metropolitano San Atón de Badajoz según consta en su archivo

La visita pastoral fue uno de los instrumentos utilizados por la Iglesia para incidir en los fines reformistas surgidos de Trento. Los obispos estaban obligados a realizarla en sus diócesis, aunque era frecuente que se realizasen por los respectivos vicarios. En el presente artículo estudiamos las visitas que los obispos Ramón Torrijos Gómez y Félix Soto Mancera realizaron al Seminario Metropolitano de San Atón de Badajoz, a principios del siglo XX, y que han quedado reflejadas en la documentación conservada en el archivo de la entidad como una prueba testimonial de la importancia que los prelados concedían a este centro formativo de referencia en la provincia de Badajoz.The pastoral visit was one of the instruments used by the church to influence the purposes of Trent reforms were. The bishops were obliged to perform it in their dioceses, but were frequently made by the respective vicars. In the current article, we study visits bishops Ramón Gómez Torrijos and Felix Soto Mancera performed at the Metropolitan Seminary of San Aton of Badajoz in the early twentieth century and are reflected in the documentation in the file of the institution.peerReviewe

Análisis de la estructura temporal de la Archivística Eclesiástica

El presente tiene como finalidad la confección de las bases que conforman la Archivística eclesiástica. Para ello estableceremos periodos de cierta homogeneidad histórica, además tendremos en cuenta las etapas que constituyen la historia de la Archivística general y hablaremos así de cuatro grandes momentos: la archivística como instrumento inductivo y funcional, la archivística como doctrina patrimonial y jurídico-administrativa, la archivística como desarrollo historiográfico y la archivística en la sociedad del conocimiento. De todo ello, inferimos que dichos espacios de inteligibilidad son básicos para la comprensión de la historia de la archivística eclesiástica.The main objective of this article is to build up baselines for a History of Ecclesiasctic Archival. For this purpose, we will establish periods of certain historical homogeneity, moreover We will bear in mind the stages of the general Archival history and we will speak about four big moments: Archival science as an inductive and functional instrument, Archival science as patrimonial and legal-administrative field, Archival science as a historiographic development, and Archival science in knowledge society. In consequence, we infer as a main result that understanding spaces are basic for comprehension of archival science cultural history, a ground-breaking concept

Adapting Web Services for Multiple Devices: a Model-Driven, Aspect-Oriented Approach

Mobile devices have become an essential element in our daily lives, even for connecting to the Internet. Web Services have become extremely important when offering services through the Internet. However, current Web Services are very inflexible as regards their invocation from different types of device, especially if we consider the need for them to be adaptable when being invoked from a mobile device. In this paper, we will propose several alternatives for the creation of flexible web services which can be invoked from different types of device, and compare the different proposed approaches. Aspect -Oriented Programming and Model-Driven Development have been used in all proposals to reduce the impact of service adaption, not only for the service developer, but also to maintain the correct code structure. This work has been developed thanks to the support of MEC (contract TIN2008-02985)