The strategic impact of META-NET on the regional, national and international level

This article provides an overview of the dissemination work carried out in META-NET from 2010 until early 2014; we describe its impact on the regional, national and international level, mainly with regard to politics and the situation of funding for LT topics. This paper documents the initiative’s work throughout Europe in order to boost progress and innovation in our field.Postprint (published version

Estimating uncertainty of alcohol-attributable fractions for infectious and chronic diseases

Background: Alcohol is a major risk factor for burden of disease and injuries globally. This paper presents a systematic method to compute the 95% confidence intervals of alcohol-attributable fractions (AAFs) with exposure and risk relations stemming from different sources.Methods: The computation was based on previous work done on modelling drinking prevalence using the gamma distribution and the inherent properties of this distribution. The Monte Carlo approach was applied to derive the variance for each AAF by generating random sets of all the parameters. A large number of random samples were thus created for each AAF to estimate variances. The derivation of the distributions of the different parameters is presented as well as sensitivity analyses which give an estimation of the number of samples required to determine the variance with predetermined precision, and to determine which parameter had the most impact on the variance of the AAFs.Results: The analysis of the five Asian regions showed that 150 000 samples gave a sufficiently accurate estimation of the 95% confidence intervals for each disease. The relative risk functions accounted for most of the variance in the majority of cases.Conclusions: Within reasonable computation time, the method yielded very accurate values for variances of AAFs

Low Mach Number Modeling of Type Ia Supernovae

We introduce a low Mach number equation set for the large-scale numerical simulation of carbon-oxygen white dwarfs experiencing a thermonuclear deflagration. Since most of the interesting physics in a Type Ia supernova transpires at Mach numbers from 0.01 to 0.1, such an approach enables both a considerable increase in accuracy and savings in computer time compared with frequently used compressible codes. Our equation set is derived from the fully compressible equations using low Mach number asymptotics, but without any restriction on the size of perturbations in density or temperature. Comparisons with simulations that use the fully compressible equations validate the low Mach number model in regimes where both are applicable. Comparisons to simulations based on the more traditional anelastic approximation also demonstrate the agreement of these models in the regime for which the anelastic approximation is valid. For low Mach number flows with potentially finite amplitude variations in density and temperature, the low Mach number model overcomes the limitations of each of the more traditional models and can serve as the basis for an accurate and efficient simulation tool.Comment: Accepted for publication in the Astrophysical Journal 31 pages, 5 figures (some figures degraded in quality to conserve space

Systematics of heavy-ion fusion hindrance at extreme sub-barrier energies

The recent discovery of hindrance in heavy-ion induced fusion reactions at extreme sub-barrier energies represents a challenge for theoretical models. Previously, it has been shown that in medium-heavy systems, the onset of fusion hindrance depends strongly on the "stiffness" of the nuclei in the entrance channel. In this work, we explore its dependence on the total mass and the $Q$-value of the fusing systems and find that the fusion hindrance depends in a systematic way on the entrance channel properties over a wide range of systems.Comment: Submitted to Phys. Rev. Lett., 5 pages, 3 figure

Quantification of p38/synaptophysin in highly purified adrenal medullary chromaffin vesicles

p38/synaptophysin is a membrane protein present in clear (synaptic) vesicles of neurons and endocrine ceHs [1-4]. From the amino acid sequence deduced from cDNAs encoding p38/synaptophysin, a model with several membrane spanning polypeptide segments and a carboxy-terminal protein domain exposed to the cytoplasmic surface has been constructed [5-7]. The function of p38/synaptophysin is not known. It has been suggested to form a transmembrane channel for ions, or to interact with cytoplasmic factors via its cytoplasmic domain [7]. Since synaptophysin binds Ca2 +, it may also play a role in the release of neurotransmitters stored in clear (synaptic) vesicles [3]. Recently it has been reported [8] that p38/synaptophysin also occurs in hormone containing large dense core vesicles. This would imply that p38/synaptophysin could fulfill similar functions as described above in chromaffin and other secretory ceHs containing large dense core vesicles. In dear (synaptic) vesicles p38/synaptophysin constitutes 7.51Jfo of the vesicle membrane proteins [I]. The amount of p38/synaptophysin in large dense core vesides is not known. Here we report on the quantification of p38/synaptophysin in highly purified chromaffin secretory veside

Linear approaches to intramolecular Förster Resonance Energy Transfer probe measurements for quantitative modeling

Numerous unimolecular, genetically-encoded Forster Resonance Energy Transfer (FRET) probes for monitoring biochemical activities in live cells have been developed over the past decade. As these probes allow for collection of high frequency, spatially resolved data on signaling events in live cells and tissues, they are an attractive technology for obtaining data to develop quantitative, mathematical models of spatiotemporal signaling dynamics. However, to be useful for such purposes the observed FRET from such probes should be related to a biological quantity of interest through a defined mathematical relationship, which is straightforward when this relationship is linear, and can be difficult otherwise. First, we show that only in rare circumstances is the observed FRET linearly proportional to a biochemical activity. Therefore in most cases FRET measurements should only be compared either to explicitly modeled probes or to concentrations of products of the biochemical activity, but not to activities themselves. Importantly, we find that FRET measured by standard intensity-based, ratiometric methods is inherently non-linear with respect to the fraction of probes undergoing FRET. Alternatively, we find that quantifying FRET either via (1) fluorescence lifetime imaging (FLIM) or (2) ratiometric methods where the donor emission intensity is divided by the directly-excited acceptor emission intensity (denoted R<sub>alt</sub>) is linear with respect to the fraction of probes undergoing FRET. This linearity property allows one to calculate the fraction of active probes based on the FRET measurement. Thus, our results suggest that either FLIM or ratiometric methods based on R<sub>alt</sub> are the preferred techniques for obtaining quantitative data from FRET probe experiments for mathematical modeling purpose