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

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

Research in Mathematics Education through Spanish scholarly publications

Se presenta un estudio bibliométrico y de análisis de las redes de colaboración en los artículos de investigación en Educación Matemática publicados en una muestra de revistas españolas en el período 1999-2008. Para ello se han analizado los 774 artículos publicados en un conjunto de ocho revistas españolas representativas verificándose el cumplimiento de las leyes o patrones propios de la Cienciometría y comprobándose un bajo grado de colaboración científica entre los investigadores del área y también entre las institucionesWe present a bibliometric study of research articles on mathematics education, as well as an analysis of networks of collaboration in the same, based on a sample of Spanish journals published during the period 1999-2008. For this purpose we analyzed 774 articles published in the eight most representative Spanish journals in the fi eld. The results show compliance with scientometric laws and patterns, as well as verifying the low level of scientifi c collaboration among researchers in the area, as well as among institution

The weighted independent domination problem: ILP model and algorithmic approaches

This work deals with the so-called weighted independent domination problem, which is an N P -hard combinatorial optimization problem in graphs. In contrast to previous theoretical work from the liter- ature, this paper considers the problem from an algorithmic perspective. The first contribution consists in the development of an integer linear programming model and a heuristic that makes use of this model. Sec- ond, two greedy heuristics are proposed. Finally, the last contribution is a population-based iterated greedy algorithm that takes profit from the better one of the two developed greedy heuristics. The results of the compared algorithmic approaches show that small problem instances based on random graphs are best solved by an efficient integer linear programming solver such as CPLEX. Larger problem instances are best tackled by the population-based iterated greedy algorithm. The experimental evaluation considers random graphs of different sizes, densities, and ways of generating the node and edge weights

The Weighted Independent Domination Problem: ILP Model and Algorithmic Approaches

This work deals with the so-called weighted independent domination problem, which is an $NP$-hard combinatorial optimization problem in graphs. In contrast to previous work, this paper considers the problem from a non-theoretical perspective. The first contribution consists in the development of three integer linear programming models. Second, two greedy heuristics are proposed. Finally, the last contribution is a population-based iterated greedy metaheuristic which is applied in two different ways: (1) the metaheuristic is applied directly to each problem instance, and (2) the metaheuristic is applied at each iteration of a higher-level framework---known as construct, merge, solve \& adapt---to sub-instances of the tackled problem instances. The results of the considered algorithmic approaches show that integer linear programming approaches can only compete with the developed metaheuristics in the context of graphs with up to 100 nodes. When larger graphs are concerned, the application of the populated-based iterated greedy algorithm within the higher-level framework works generally best. The experimental evaluation considers graphs of different types, sizes, densities, and ways of generating the node and edge weights