Quantitative sequence analysis of FBN1 premature termination codons provides evidence for incomplete NMD in leukocytes.

We improved, evaluated, and used Sanger sequencing for quantification of single nucleotide polymorphism (SNP) variants in transcripts and gDNA samples. This improved assay resulted in highly reproducible relative allele frequencies (e.g., for a heterozygous gDNA 50.0+/-1.4%, and for a missense mutation-bearing transcript 46.9+/-3.7%) with a lower detection limit of 3-9%. It provided excellent accuracy and linear correlation between expected and observed relative allele frequencies. This sequencing assay, which can also be used for the quantification of copy number variations (CNVs), methylations, mosaicisms, and DNA pools, enabled us to analyze transcripts of the FBN1 gene in fibroblasts and blood samples of patients with suspected Marfan syndrome not only qualitatively but also quantitatively. We report a total of 18 novel and 19 known FBN1 sequence variants leading to a premature termination codon (PTC), 26 of which we analyzed by quantitative sequencing both at gDNA and cDNA levels. The relative amounts of PTC-containing FBN1 transcripts in fresh and PAXgene-stabilized blood samples were significantly higher (33.0+/-3.9% to 80.0+/-7.2%) than those detected in affected fibroblasts with inhibition of nonsense-mediated mRNA decay (NMD) (11.0+/-2.1% to 25.0+/-1.8%), whereas in fibroblasts without NMD inhibition no mutant alleles could be detected. These results provide evidence for incomplete NMD in leukocytes and have particular importance for RNA-based analyses not only in FBN1 but also in other genes.

Gestión de pedidos e incidencias

Aplicación web desarrollada en J2EE para la gestión de pedidos en incidencias de sedes remotas a la central.

Análisis empírico de la discriminación salarial por género y etnia en el Ecuador en el año 2008

La población femenina y la indígena del Ecuador han presentado continuamente desigualdades de ingresos respecto a la población masculina y a la no indígena, respectivamente. El presente trabajo reporta que una parte de las diferencias salariales a favor de los hombres y de la población no indígena es resultado de la discriminación salarial por razones de género y etnia. Este resultado se ha obtenido estimando ecuaciones mincerianas de ingresos corrigiendo el problema de se sgo de selección muestral y utilizando la metodología de descomposición de las brechas salariales de Oaxaca (1973) y Newmak (1988) también corregidas por el problema de sesgo de selección muestral.

Point Mutations in the Monocarboxylate Transporter SLC16A12 Lead to Juvenile and Age-Related Cataract

Purpose: Previously we reported on a premature termination mutation in SLC16A12 that leads to dominant juvenile cataract and renal glucosuria. To assess the mutation rate and genotype-phenotype correlations of SLC16A12 in juvenile or age-related forms of cataract, we performed a mutation screen in cataract patients. Methods: Clinical data of approximately 660 patients were collected, genomic DNA was isolated and analyzed. Exons 3 to 8 including flanking intron sequences of SLC16A12 were PCR amplified and DNA sequence was determined. Selected mutations were tested by cell culture assays, in silico analysis and RT-PCR. Results: We found sequence alterations at a rate of approximately 1/75 patients. None of them was found in 360 control alleles. Alterations affect splice site and regulatory region but most mutations caused an amino acid substitution. The majority of the coding region mutations maps to trans-membrane domains. One mutation located to the 5'UTR. It affects translational efficiency of SLC16A12. In addition, we identified a cataract-predisposing SNP in the non-coding region that causes allele-specific splicing of the 5'UTR region. Conclusions: Altered translational efficiency of the solute carrier SLC16A12 and its allele-specific splicing strongly support a model of challenged homeostasis to cause various forms of cataract. In addition, the pathogenic property of the here reported sequence alterations is supported by the lack of known sequence variations within the coding region of SLC16A12. Due to the relatively high mutation rate, we suggest to include SLC16A12 in diagnostic cataract screening. Generally, our data recommend the assessment of regulatory sequences for diagnostic purposes.

La Competitividad de las exportaciones de vino español y el mercado mundial 1960-2011

Este trabajo analiza la evolución y competitividad de las exportaciones españolas de vino en el mercado mundial desde la década de 1960. Con ello explora las respuestas de la industria vinícola durante la globalización del vino. Analiza el comportamiento evolutivo del sector por tipos de vinos y el peso relativo de las exportaciones en volumen, valor y precios unitarios en el mercado mundial. El estudio de la ventaja comparativa del comercio exterior se realiza a través del índice de Ventaja Competitiva Revelada (VCR) o Índice de Balassa. Demuestra que pese al fabuloso crecimiento de las exportaciones entre 1960 y 2011 la industria española sigue especializada en vinos de bajo coste y en exportaciones a granel. Aunque mejoró la calidad y crecieron las exportaciones de vinos embotellados con denominación de origen, la competitividad del sector muestra serias debilidades que la sitúan entre las más bajas de los países especializados.

Influencia del lenguaje y lugar de origen de un lector en la formación de conductas

El estudio examinó la posible influencia del lenguaje y lugar de origen de un lector en la comprensión de mensajes de comunicación en salud y en la formación de actitud e intención de conductas preventivas. Un instrumento de medición con escala de comprensión de lectura, actitud e intención fue suministrado a un grupo de puertorriqueños y dominicanos (N=40) residentes en San Juan, Puerto Rico. La escala de comprensión tenía dos textos en diversos niveles de dificultad (bastante fácil y medio) de acuerdo con la Fórmula de Legibilidad para el idioma español de Francisco Szigriszt Pazos. Los análisis estadísticos revelaron que no se encontró diferencia estadística significativa (p>.05) en las medias aritméticas de las respuestas correctas al comparar los dos niveles de dificultad entre los participantes. No hubo diferencia estadística significativa (p>.05) entre la muestra en el nivel de dificultad bastante fácil, no obstante en el nivel de dificultad medio hubo diferencia estadística significativa (p<.05). Los análisis de regresión reflejaron que la comprensión y actitud en conjunto no predicen de manera significativa el grado de intención para la adopción de una conducta preventiva de salud.

El lenguaje: herramienta de reconstrucción del pensamiento

La idea de que el lenguaje ha transformado la conciencia humana porque permite el desarrollo de nuevas formas de pensamiento y la adquisición de conocimientos, nos lleva a buscar una explicación teórica sobre las relaciones existentes entre el pensamiento, lenguaje y su posible relación en la determinación de acciones de un receptor. En este escrito sepresenta un análisis teórico sobre algunos conceptos que componen el lenguaje y su potencial injerencia en los procesos de comunicación social.

Genome-wide screen of genes required for caffeine tolerance in fission yeast

Background: An excess of caffeine is cytotoxic to all eukaryotic cell types. We aim to study how cells become tolerant to atoxic dose of this drug, and the relationship between caffeine and oxidative stress pathways.Methodology/Principal Findings: We searched for Schizosaccharomyces pombe mutants with inhibited growth on caffeinecontainingplates. We screened a collection of 2,700 haploid mutant cells, of which 98 were sensitive to caffeine. The genes mutated in these sensitive clones were involved in a number of cellular roles including the H2O2-induced Pap1 and Sty1 stress pathways, the integrity and calcineurin pathways, cell morphology and chromatin remodeling. We have investigated the role of the oxidative stress pathways in sensing and promoting survival to caffeine. The Pap1 and the Sty1 pathways are both required for normal tolerance to caffeine, but only the Sty1 pathway is activated by the drug. Cells lacking Pap1 aresensitive to caffeine due to the decreased expression of the efflux pump Hba2. Indeed, ?hba2 cells are sensitive to caffeine, and constitutive activation of the Pap1 pathway enhances resistance to caffeine in an Hba2-dependent manner. Conclusions/Significance: With our caffeine-sensitive, genome-wide screen of an S. pombe deletion collection, we havedemonstrated the importance of some oxidative stress pathway components on wild-type tolerance to the drug.

Collage, a Collaborative Learning Design Editor Based on Patterns

This paper introduces Collage, a high-level IMS-LD compliant authoring tool that is specialized for CSCL (Computer-Supported Collaborative Learning). Nowadays CSCL is a key trend in elearning since it highlights the importance of social interactions as an essential element of learning. CSCL is an interdisciplinary domain, which demands participatory design techniques that allow teachers to get directly involved in design activities. Developing CSCL designs using LD is a difficult task for teachers since LD is a complex technical specification and modelling collaborative characteristics can be tricky. Collage helps teachers in the process of creating their own potentially effective collaborative Learning Designs by reusing and customizing patterns, according to the requirements of a particular learning situation. These patterns, called Collaborative Learning Flow Patterns (CLFPs), represent best practices that are repetitively used by practitioners when structuring the flow of (collaborative) learning activities. An example of an LD that can be created using Collage is illustrated in the paper. Preliminary evaluation results show that teachers, with experience in CL but without LD knowledge, can successfully design real collaborative learning experiences using Collage.

A multicase study for the evaluation of a pattern-based visual design process for collaborative learning

Collage is a pattern-based visual design authoring tool for the creation of collaborative learning scripts computationally modelled with IMS Learning Design (LD). The pattern-based visual approach aims to provide teachers with design ideas that are based on broadly accepted practices. Besides, it seeks hiding the LD notation so that teachers can easily create their own designs. The use of visual representations supports both the understanding of the design ideas and the usability of the authoring tool. This paper presents a multicase study comprising three different cases that evaluate the approach from different perspectives. The first case includes workshops where teachers use Collage. A second case implies the design of a scenario proposed by a third-party using related approaches. The third case analyzes a situation where students follow a design created with Collage. The cross-case analysis provides a global understanding of the possibilities and limitations of the pattern-based visual design approach.

Free-and open source software for a course on network management: authoring and enactment of scripts based on collaborative learning strategies

This paper describes a Computer-Supported Collaborative Learning (CSCL) case study in engineering education carried out within the context of a network management course. The case study shows that the use of two computing tools developed by the authors and based on Free- and Open-Source Software (FOSS) provide significant educational benefits over traditional engineering pedagogical approaches in terms of both concepts and engineering competencies acquisition. First, the Collage authoring tool guides and supports the course teacher in the process of authoring computer-interpretable representations (using the IMS Learning Design standard notation) of effective collaborative pedagogical designs. Besides, the Gridcole system supports the enactment of that design by guiding the students throughout the prescribed sequence of learning activities. The paper introduces the goals and context of the case study, elaborates onhow Collage and Gridcole were employed, describes the applied evaluation methodology, anddiscusses the most significant findings derived from the case study.

Reusing IMS-LD formalized best practices in collaborative learning structuring

Designs of CSCL (Computer Supported Collaborative Learning)activities should be flexible, effective and customizable toparticular learning situations. On the other hand, structureddesigns aim to create favourable conditions for learning. Thus,this paper proposes the collection of representative and broadlyaccepted (best practices) structuring techniques in collaborative learning. With the aim of establishing a conceptual common ground among collaborative learning practitioners and softwaredevelopers, and reusing the expertise that best practicesrepresent, the paper also proposes the formulation of these techniques as patterns: the so-called CLFPs (CollaborativeLearning Flow Patterns). To formalize these patterns, we havechosen the educational modelling language IMS Learning Design (IMS-LD). IMS-LD has the capability to specify many of the collaborative characteristics of the CLFPs. Nevertheless, the language bears limited capability for describing the services that mediate interactions within a learning activity and the specification of temporal or rotated roles. This analysis isdiscussed in the paper, as well as our approaches towards thedevelopment of a system capable of integrating tools using IMSLDscripts and a CLFP-based Learning Design authoring tool.

Wii-immersion: aprovechando las capacidades del Wiimote para la mejora de la sensación de inmersión

En este proyecto se proponen dos utilidades para mejorar la sensación de inmersión en un entorno virtual. Ambas utilidades pretenden aportar una interacción más intuitiva. Para ello, las dos se basan en capturar el movimiento del usuario a través de distintos dispositivos. En la primera utilidad se obtiene la posición de la cabeza del usuario y se visualiza la escena en base a dicha posición. Esto se consigue usando un Wiimote a modo de cámara infra-roja en combinación con unas gafas con leds infra-rojos para determinar la posición de la cabeza. La segunda utilidad consiste en un control gestual con seis grados de libertad. El control gestual permite manipular un objeto real, es decir, trasladarlo y rotarlo y que dicha manipulación se refleje en un objeto virtual. Manipulando el objeto es posible interactuar con el entorno virtual visualizado mediante el GTI Framework. La manipulación del control gestual permite interactuar de una forma muy natural, similar a como se interactuaría en un entorno real. Como objeto real se ha empleado un Wiimote en combinación con el periférico Motion Plus y una esfera luminosa ubicada en su extremo. El Motion Plus permite obtener la orientación, y mediante una cámara PlayStation Eye se detecta la esfera, que determina la posición del Wiimote