Optimal Strategies for Second Guessers

A model is given for a class of contests in which the participants try to guess (or estimate) unknown quantities, and the objective of each player is to come closer to the unknown quantities than an adversary. A general optimality result is proved that gives the best guessing rules for the second guesser. These rules are first calculated exactly in a certain hierarchical linear model, and then simpler approximate rules are given

Enhanced C/EBPβ function promotes hypertrophic versus hyperplastic fat tissue growth and prevents steatosis in response to high-fat diet feeding

Chronic obesity is correlated with severe metabolic and cardiovascular diseases as well as with an increased risk for developing cancers. Obesity is usually characterized by fat accumulation in enlarged-hypertrophic – adipocytes that are a source of inflammatory mediators, which promote the development and progression of metabolic disorders. Yet, in certain healthy obese individuals, fat is stored in metabolically more favorable hyperplastic fat tissue that contains an increased number of smaller adipocytes that are less inflamed. In a previous study we demonstrated that loss of the inhibitory protein-isoform C/EBPβ-LIP and the resulting augmented function of the transactivating isoform C/EBPβ-LAP promotes fat metabolism under normal feeding conditions and expands health-and lifespan in mice. Here we show that in mice on a high-fat diet, LIP-deficiency results in adipocyte hyperplasia associated with reduced inflammation and metabolic improvements. Furthermore, fat storage in subcutaneous depots is significantly enhanced specifically in LIP-deficient male mice. Our data identify C/EBPβ as a regulator of adipocyte fate in response to increased fat intake, which has major implications for metabolic health and aging

A multidisciplinary engineering summer school in an industrial setting

Most university-level engineering studies produce technically skilled engineers. However, typically students face several difficulties whenworking in multidisciplinary teams when they initiate their industrial careers. In a globalised world, it becomes increasingly important that engineers are capable of collaborating across disciplinary boundaries and exhibit soft competencies, like communication, interpersonal and social skills, time planning, creativity, initiative, and reflection. To prepare a group of engineering and industrial design students to acquire those capabilities, an international summer school that combined industrial design with different kinds of engineering disciplineswas organised on the site of Bang&Olufsen (B&O) in Denmark. This multidisciplinary engineering summer school was attended by students from six European university-level teaching institutions and was supervised by teachers from those institutions and industrial experts from B&O. The main aim of the summer school was to allow students to work in teams, composed of students from different knowledge disciplines and with different cultural backgrounds, with the purpose of developing innovative concepts and products, within a strong industrial perspective.B&OERASMU

The enzymatic activity of the VEGFR2-receptor for the biosynthesis of dinucleoside polyphosphates

The group of dinucleoside polyphosphates encompasses a large number of molecules consisting of two nucleosides which are connected by a phosphate chain of variable length. While the receptors activated by dinucleoside polyphosphates as well as their degradation have been studied in detail, its biosynthesis has not been elucidated so far. Since endothelial cells released the dinucleoside polyphosphate uridine adenosine tetraphosphate (Up4A), we tested cytosolic proteins of human endothelial cells obtained from dermal vessels elicited for enzymatic activity. When incubated with ADP and UDP, these cells showed increasing concentrations of Up4A. The underlying enzyme was isolated by chromatography and the mass spectrometric analysis revealed that the enzymatic activity was caused by the vascular endothelial growth factor receptor 2 (VEGFR2). Since VEGFR2 but neither VEGFR1 nor VEGFR3 were capable to synthesise dinucleoside polyphosphates, Tyr-1175 of VEGFR2 is most likely essential for the enzymatic activity of interest. Further, VEGFR2-containing cells like HepG2, THP-1 and RAW264.7 were capable of synthesising dinucleoside polyphosphates. VEGFR2-transfected HEK 293T/17 but not native HEK 293T/17 cells synthesised dinucleoside polyphosphates in vivo too. The simultaneous biosynthesis of dinucleoside polyphosphates could amplify the response to VEGF, since dinucleoside polyphosphates induce cellular growth via P2Y purinergic receptors. Thus the biosynthesis of dinucleoside polyphosphates by VEGFR2 may enhance the proliferative response to VEGF. Given that VEGFR2 is primarily expressed in endothelial cells, the biosynthesis of dinucleoside polyphosphates is mainly located in the vascular system. Since the vasculature is also the main site of action of dinucleoside polyphosphates, activating vascular purinoceptors, blood vessels appear as an autocrine system with respect to dinucleoside polyphosphates. We conclude that VEGFR2 receptor is capable of synthesising dinucleoside polyphosphates. These mediators may modulate the effects of VEGFR2 due to their proliferative effects

Effect of amlodipine on cardiovascular events in hypertensive haemodialysis patients

Background. Hypertensive haemodialysis patients may be at a high risk for cardiovascular events. This study was undertaken to ascertain whether the calcium channel blocker amlodipine reduces mortality and cardiovascular events in these high-risk patients

Targeting of the Plzf gene in the rat by transcription activator-like effector nuclease results in caudal regression syndrome in spontaneously hypertensive rats

Recently, it has been found that spontaneous mutation Lx (polydactyly-luxate syndrome) in the rat is determined by deletion of a conserved intronic sequence of the Plzf (Promyelocytic leukemia zinc finger protein) gene. In addition, Plzf is a prominent candidate gene for quantitative trait loci (QTLs) associated with cardiac hypertrophy and fibrosis in the spontaneously hypertensive rat (SHR). In the current study, we tested the effects of Plzf gene targeting in the SHR using TALENs (transcription activator-like effector nucleases). SHR ova were microinjected with constructs pTAL438/439 coding for a sequence-specific endonuclease that binds to target sequence in the first coding exon of the Plzf gene. Out of 43 animals born after microinjection, we detected a single male founder. Sequence analysis revealed a deletion of G that resulted in frame shift mutation starting in codon 31 and causing a premature stop codon at position of amino acid 58. The Plzftm1Ipcv allele is semi-lethal since approximately 95% of newborn homozygous animals died perinatally. All homozygous animals exhibited manifestations of a caudal regression syndrome including tail anomalies and serious size reduction and deformities of long bones, and oligo- or polydactyly on the hindlimbs. The heterozygous animals only exhibited the tail anomalies. Impaired development of the urinary tract was also revealed: one homozygous and one heterozygous rat exhibited a vesico-ureteric reflux with enormous dilatation of ureters and renal pelvis. In the homozygote, this was combined with a hypoplastic kidney. These results provide evidence for the important role of Plzf gene during development of the caudal part of a body-column vertebrae, hindlimbs and urinary system in the rat