A novel selective 11b-hydroxysteroid dehydrogenase type 1 inhibitor prevents human adipogenesis.

Glucocorticoid excess increases fat mass, preferentially within omental depots; yet circulating cortisol concentrations are normal in most patients with metabolic syndrome (MS). At a pre-receptor level, 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) activates cortisol from cortisone locally within adipose tissue, and inhibition of 11b-HSD1 in liver and adipose tissue has been proposed as a novel therapy to treat MS by reducing hepatic glucose output and adiposity. Using a transformed human subcutaneous preadipocyte cell line (Chub-S7) and human primary preadipocytes, we have defined the role of glucocorticoids and 11b-HSD1 in regulating adipose tissue differentiation. Human cells were differentiated with 1.0 mM cortisol (F), or cortisone (E) with or without 100 nM of a highly selective 11b-HSD1 inhibitor PF-877423. 11b-HSD1 mRNA expression increased across adipocyte differentiation (P!0.001, nZ4), which was paralleled by an increase in 11b-HSD1 oxo-reductase activity (from nil on day 0 to 5.9G1.9 pmol/mg per h on day 16,P!0.01, nZ7). Cortisone enhanced adipocyte differentiation; fatty acid-binding protein 4 expression increased 312-fold (P!0.001) and glycerol-3-phosphate dehydrogenase 47-fold (P!0.001) versus controls. This was abolished by co-incubation with PF-877423. In addition, cellular lipid content decreased significantly. These findings were confirmed in the primary cultures of human subcutaneous preadipocytes. The increase in 11b-HSD1 mRNA expression and activity is essential for the induction of human adipogenesis. Blocking adipogenesis with a novel and specific 11b-HSD1 inhibitor may represent a novel approach to treat obesity in patients with MS

Coverage Based Testing for Service Level Agreements

Service level agreements (SLAs) are typically used to specify rules regarding the consumption of services that are agreed between the providers of the service-based applications (SBAs) and their consumers. An SLA includes a list of terms that contain the guarantees that must be fulfilled during the provisioning and consumption of the services. Since the violation of such guarantees may lead to the application of potential penalties, it is important to assure that the SBA behaves as expected. In this paper, we propose a proactive approach to test SLA-aware SBAs by means of identifying test requirements, which represent situations that are relevant to be tested. To address this issue, we define a four-valued logic that allows evaluating both the individual guarantee terms and their logical relationships. Grounded in this logic, we devise a test criterion based on the modified condition decision coverage (MCDC) in order to obtain a cost-effective set of test requirements from the structure of the SLA. Furthermore by analyzing the syntax and semantics of the agreement, we define specific rules to avoid non-feasible test requirements. The whole approach has been automated and applied over an eHealth case study

Bibliografía usada en la formación matemática del profesorado de infantil

Para realizar el estudio se escogió una muestra de 13 universidades españolas en las que se imparte la titulación y cuyas guías docentes son accesibles desde sus páginas webs. Se descargaron todas las guías docentes y se pasó la información a una base de datos ad hoc. Se realizó un proceso de estandarización de los nombres y de las referencias porque para cada asignatura utilizan formatos distintos incluso en la misma universidad. Se obtuvieron 493 referencias, que se presentan como bibliografía básica, específica, recomendada o complementaria. Posteriormente se hicieron conteos de frecuencias de cada autor, referencia y año para determinar la antigüedad de las mismas

Identifying Test Requirements by Analyzing SLA Guarantee Terms

Service Level Agreements (SLAs) are used to specify the negotiated conditions between the provider and the consumer of services. In this paper we present a stepwise method to identify and categorize a set of test requirements that represent the potential situations that can be exercised regarding the specification of each isolated guarantee term of an SLA. This identification is addressed by means of devising a set of coverage levels that allow grading the thoroughness of the tests. The utilization of these test requirements would focus on twofold objectives: (1) the generation of a test suite that allows exercising the situations described in the test requirements and (2) the support for the derivation of a monitoring plan that checks the compliance of these requirements at runtime. The approach is illustrated over an eHealth case study

Possible regulation of CFTR-chloride channels by membrane-bound phosphatases in pancreatic duct cells

AbstractWe have studied CFTR-Cl− channels in non-CF CAPAN-1 and in CFTR-transfected CFPAC-PLJ-CFTR-6 epithelial cells from human pancreas. Theophylline and IBMX induced the opening of cell-attached CFTR-Cl− channels. Theophylline, IBMX and the alkaline phosphatase (AP) inhibitor levamisole enhanced the activity of excised channels and reduced by 70–75% the apical membrane-associated APs activity. Okadaic acid had no effect on APs and channel activities. A polyclonal anti-alkaline phosphatase antibody (which detected apical APs) reduced APs activity and activated quiescent excised chloride channels. These results suggest that CFTR channels may be regulated by membrane-bound phosphatases

Is profitable to play in Spanish Soccer First Division?

El artículo presenta la primera fase de un estudio del fútbol español, cuyo objetivo es averiguar si es rentable jugar en Primera División de fútbol (1ª) para cualquier equipo profesional y si todos los clubes de 2ªA deberían aspirar al ascenso. Se comparan resultados en la población seleccionada y en dos grupos de la misma: equipos que se han mantenido en 1ª y equipos ascensor. Se examinan mediante análisis exploratorio de datos resultados económicos y deportivos, se identifican factores que influyen en su variación y se clasifican los clubes según dichos factores. También se determina la influencia de ascensos y descensos en los resultados. Se deduce que los equipos ascensor obtienen peores resultados aun jugando en la misma liga. Además, a su estabilidad económico financiera le afecta más el ascenso y descenso continuo que el mantenerse en una categoría concreta. Finalmente, que la “gestión del miedo” no siempre conduce a una mejor clasificación y añade tensión financiera. Se concluye que no a todos los clubes les conviene militar en 1ª división de fútbol, que ésta debe reestructurarse y se debe reforzar la 2ªAThe paper presents the first phase of a Spanish football study. The aim is to determine if it is profitable to play in 1ª D league for any professional team and if all clubs in 2ª A division should aspire to climb. Various results are compared in the selected population and also in two groups identified: equipment that have remained in 1ªD and “elevator teams”. The economics and sports results are examined by exploratory data analysis. We identify factors that are influence in change and the teams are classified according to these factors. Finally the influence of promotion and relegation in these results is determined. It follows that the "Fear Management" doesn’t always lead to better classification and adds financial stress, “elevator equipment” that perform worse even playing in the same league and its economic and financial stability will most affect the rise and decline that continued the stay in a particular category. We conclude: not all clubs suit them military in 1ª, it would be to restructure and strengthen the 2ª

Interference alignment testbeds

Interference alignment has triggered high impact research in wireless communications since it was proposed nearly 10 years ago. However, the vast majority of research is centered on the theory of interference alignment and is hardly feasible in view of the existing state-of-the-art wireless technologies. Although several research groups have assessed the feasibility of interference alignment via testbed measurements in realistic environments, the experimental evaluation of interference alignment is still in its infancy since most of the experiments were limited to simpler scenarios and configurations. This article summarizes the practical limitations of experimentally evaluating interference alignment, provides an overview of the available interference alignment testbed implementations, including the costs, and highlights the imperatives for succeeding interference alignment testbed implementations. Finally, the article explores future research directions on the applications of interference alignment in the next generation wireless systems.Jacobo Fanjul's research has been supported by the Ministerio de Economía y Competitividad (MINECO) of Spain, under grants TEC2013-47141-C4-R (RACHEL project) and FPI grant BES-2014-069786. José A. García-Naya's research has been funded by the Xunta de Galicia (ED431C 2016–045, ED341D R2016/012, E0431 G/01), the Agencia Estatal de Investigación of Spain (TEC2013-47141-C4-1-R, TEC2015-69648-REOC, TEC2016-75067-C4-1-R), and ERDF funds of the EU (AEI/FEDER, UE). Hamed Farhadi's research has been funded by the Swedish Research Council (VR) under grant 2015–00500

Nutrient and herbivore alterations cause uncoupled changes in producer diversity, biomass and ecosystem function, but not in overall multifunctionality

Altered nutrient cycles and consumer populations are among the top anthropogenic influences on ecosystems. However, studies on the simultaneous impacts of human-driven environmental alterations on ecosystem functions, and the overall change in system multifunctionality are scarce. We used estuarine tidal flats to study the effects of changes in herbivore density and nutrient availability on benthic microalgae (diversity, abundance and biomass) and ecosystem functions (N2-fixation, denitrification, extracellular polymeric substances -EPS- as a proxy for sediment cohesiveness, sediment water content as a proxy of water retention capacity and sediment organic matter). We found consistent strong impacts of modified herbivory and weak effects of increased nutrient availability on the abundance, biomass and diversity of benthic microalgae. However, the effects on specific ecosystem functions were disparate. Some functions were independently affected by nutrient addition (N2-fixation), modified herbivory (sediment organic matter and water content), or their interaction (denitrification), while others were not affected (EPS). Overall system multifunction remained invariant despite changes in specific functions. This study reveals that anthropogenic pressures can induce decoupled effects between community structure and specific ecosystem functions. Our results highlight the need to address several ecosystem functions simultaneously for better ecosystem characterization and management.Instituto de Limnología "Dr. Raul A. Ringuelet