Role of Bruton's tyrosine kinase in B cells and malignancies

Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-

Inefficiency in the German Mechanical Engineering Sector

This paper aims to examine the relative efficiency of German engineering firms using a sample of roughly 23,000 observations between 1995 and 2004. As these firms had been successful in the examination period in terms of output- and export-growth, it is expected that a majority of firms is operating quite efficiently and that the density of efficiency scores is skewed to the left. Moreover, as the German engineering industry is dominated by medium sized firms, the question arises whether these firms are the most efficient ones. Finally an increasing efficiency gap between size classes over time is important since that would be a signal for a structural problem within the industry. The analysis - using recently developed DEA methods like bootstrapping or outlier detection - contradicts the two first expectations. The firms proved to operate quite inefficiently with an overall mean of 0.69, and efficiency differs significantly with firm size whereas medium sized firms being on average the least efficient ones. When looking at changes in efficiency over time, we find a decreasing efficiency gap between size classes

Short term exendin-4 treatment reduces markers of metabolic disorders in female offspring of obese rat dams

© 2015 Elsevier Ltd. Objectives: Maternal obesity imposes significant health risks in the offspring including diabetes and dyslipidemia. We previously showed that the hypoglycaemic agent exendin-4 (Ex-4) administered from weaning can reverse the maternal impact of 'transmitted disorders' in such offspring. However daily injection for six-weeks was required and the beneficial effect may lapse upon drug withdrawal. This study aimed to investigate whether short term Ex-4 treatment during suckling period in a rodent model can reverse transmitted metabolic disorders due to maternal obesity. Methods: Maternal obesity was induced in female Sprague Dawley rats by high-fat diet feeding for 6 weeks, throughout gestation and lactation. Female offspring were treated with Ex-4 (5. μg/kg/day) between postnatal day (P) 4 and 14. Female offspring were harvested at weaning (P20). Lipid and glucose metabolic markers were measured in the liver and fat. Appetite regulators were measured in the plasma and hypothalamus. Results: Maternal obesity significantly increased body weight, fat mass, and liver weight in the offspring. There was an associated inhibition of peroxisomal proliferator activated receptor gamma coactivator 1α (PGC1α), increased fatty acid synthase (FASN) expression in the liver, and reduced adipocyte triglyceride lipase (ATGL) expression. It also increased the plasma gut hormone ghrelin and reduced glucagon-like peptide-1. Ex-4 treatment partially reversed the maternal impact on adiposity and impaired lipid metabolism in the offspring, with increased liver PGC1α and inhibition of FASN mRNA expression. Ex-4 treatment also increased the expression of a novel fat depletion gene a2-zinc-glycoprotein 1 in the fat tissue. Conclusion: Short term Ex-4 treatment during the suckling period significantly improved the metabolic profile in the offspring from the obese mothers at weaning. Long-term studies are needed to follow such offspring to adulthood to examine the sustained effects of Ex-4 in preventing the development of metabolic disease

Friction stir welding/processing of metals and alloys: A comprehensive review on microstructural evolution

The unique combination of very large strains, high temperatures and high strain rates inherent to friction stir welding (FSW) and friction stir processing (FSP) and their dependency on the processing parameters provides an opportunity to tailor the microstructure, and hence the performance of welds and surfaces to an extent not possible with fusion processe

Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle cell cultures with EPO failed to induce AKT phosphorylation and had no effect on glucose uptake or glycogen synthesis. We found that the EPO receptor gene was expressed in myotubes, but was undetectable in soleus. Together, our results indicate that EPO treatment improves glucose tolerance but does not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism.Corinne Caillaud, Mie Mechta, Heidi Ainge, Andreas N Madsen, Patricia Ruell, Emilie Mas, Catherine Bisbal, Jacques Mercier, Stephen Twigg, Trevor A Mori, David Simar and Romain Barrè

Measuring the efficiency of Serbian insurance companies

The transition period, and the still ongoing economic crisis, amplify the volatility in the domestic insurance market and forces the management of insurance companies to continuously monitor changes in the market, i.e. to identify risks and opportunities, and therefore to undertake certain activities. The focus of the business of insurance companies is based on satisfying the needs of existing and potential clients. Respecting the current situation in the insurance market in anticipation of future events, the management of insurance companies must create and implement the optimal strategy in line with the company’s capabilities. For this purpose it is necessary to measure the efficiency of the business, which is the subject of this paper where the Data Envelopment Analysis (DEA) method is applied to the case of insurance companies operating in Serbia

Performance measurement with multiple interrelated variables and threshold target levels:evidence from retail firms in the US

In this study, we developed a DEA-based performance measurement methodology that is consistent with performance assessment frameworks such as the Balanced Scorecard. The methodology developed in this paper takes into account the direct or inverse relationships that may exist among the dimensions of performance to construct appropriate production frontiers. The production frontiers we obtained are deemed appropriate as they consist solely of firms with desirable levels for all dimensions of performance. These levels should be at least equal to the critical values set by decision makers. The properties and advantages of our methodology against competing methodologies are presented through an application to a real-world case study from retail firms operating in the US. A comparative analysis between the new methodology and existing methodologies explains the failure of the existing approaches to define appropriate production frontiers when directly or inversely related dimensions of performance are present and to express the interrelationships between the dimensions of performance

Challenges during the transition from child and adolescent mental health services to adult mental health services

The transition from child and adolescent to adult mental health services for young people with mental health problems is of international concern. Despite the high prevalence of mental disorders during adolescence and their tendency to continue during adulthood, the majority of young people do not experience continuity of care. The aim of this review paper is to unravel the complexity of transitional mental healthcare to clinicians, policy makers and mental health service managers, and to address challenges to a smooth transition process at all levels