Farnesyl diphosphate synthase, the target for nitrogen-containing bisphosphonate drugs, is a peroxisomal enzyme in the model system Dictyostelium discoideum

NBP (nitrogen-containing bisphosphonate) drugs protect against excessive osteoclast-mediated bone resorption. After binding to bone mineral, they are taken up selectively by the osteoclasts and inhibit the essential enzyme FDPS (farnesyl diphosphate synthase). NBPs inhibit also growth of amoebae of Dictyostelium discoideum in which their target is again FDPS. A fusion protein between FDPS and GFP (green fluorescent protein) was found, in D. discoideum, to localize to peroxisomes and to confer resistance to the NBP alendronate. GFP was also directed to peroxisomes by a fragment of FDPS comprising amino acids 1–22. This contains a sequence of nine amino acids that closely resembles the nonapeptide PTS2 (peroxisomal targeting signal type 2): there is only a single amino acid mismatch between the two sequences. Mutation analysis confirmed that the atypical PTS2 directs FDPS into peroxisomes. Furthermore, expression of the D. discoideum FDPS–GFP fusion protein in strains of Saccharomyces cerevisiae defective in peroxisomal protein import demonstrated that import of FDPS into peroxisomes was blocked in a strain lacking the PTS2-dependent import pathway. The peroxisomal location of FDPS in D. discoideum indicates that NBPs have to cross the peroxisomal membrane before they can bind to their target

Statistical Communication Theory

Contains reports on five research projects

Statistical Communication Theory

Contains research objectives and reports on three research projects

Humanitarian aid as an integral part of the European Union's external action: the challenge of reconciling coherence and independence

The article focuses on the European Union's (EU) humanitarian aid policy. It addresses the challenge for the EU to deliver independent humanitarian aid while simultaneously seeking to establish more coherence between its external policies. The article examines how the EU tries to reconcile these potentially conflicting policy goals, both de jure and in practice. Empirically, it explores the interaction between EU humanitarian aid and development cooperation, the Common Foreign and Security Policy, and trade policy. While the independence of the humanitarian aid delivery is, for the most part, not being undermined, it remains difficult to establish positive synergies with other external policies because of institutional hurdles and legal constraints, as well as political obstacles and operational incompatibilities

Cost-benefit analysis for commissioning decisions in GEO600

Gravitational wave interferometers are complex instruments, requiring years of commissioning to achieve the required sensitivities for the detection of gravitational waves, of order 10^-21 in dimensionless detector strain, in the tens of Hz to several kHz frequency band. Investigations carried out by the GEO600 detector characterisation group have shown that detector characterisation techniques are useful when planning for commissioning work. At the time of writing, GEO600 is the only large scale laser interferometer currently in operation running with a high duty factor, 70%, limited chiefly by the time spent commissioning the detector. The number of observable gravitational wave sources scales as the product of the volume of space to which the detector is sensitive and the observation time, so the goal of commissioning is to improve the detector sensitivity with the least possible detector down time. We demonstrate a method for increasing the number of sources observable by such a detector, by assessing the severity of non-astrophysical noise contaminations to efficiently guide commissioning. This method will be particularly useful in the early stages and during the initial science runs of the aLIGO and adVirgo detectors, as they are brought up to design performance.Comment: 17 pages, 17 figures, 2 table

The neural basis of authenticity recognition in laughter and crying

Deciding whether others’ emotions are genuine is essential for successful communication and social relationships. While previous fMRI studies suggested that differentiation between authentic and acted emotional expressions involves higher-order brain areas, the time course of authenticity discrimination is still unknown. To address this gap, we tested the impact of authenticity discrimination on event-related potentials (ERPs) related to emotion, motivational salience, and higher-order cognitive processing (N100, P200 and late positive complex, the LPC), using vocalised non-verbal expressions of sadness (crying) and happiness (laughter) in a 32-participant, within-subject study. Using a repeated measures 2-factor (authenticity, emotion) ANOVA, we show that N100’s amplitude was larger in response to authentic than acted vocalisations, particularly in cries, while P200’s was larger in response to acted vocalisations, particularly in laughs. We suggest these results point to two different mechanisms: (1) a larger N100 in response to authentic vocalisations is consistent with its link to emotional content and arousal (putatively larger amplitude for genuine emotional expressions); (2) a larger P200 in response to acted ones is in line with evidence relating it to motivational salience (putatively larger for ambiguous emotional expressions). Complementarily, a significant main effect of emotion was found on P200 and LPC amplitudes, in that the two were larger for laughs than cries, regardless of authenticity. Overall, we provide the first electroencephalographic examination of authenticity discrimination and propose that authenticity processing of others’ vocalisations is initiated early, along that of their emotional content or category, attesting for its evolutionary relevance for trust and bond formation.info:eu-repo/semantics/publishedVersio

Statistical Communication Theory

Contains reports on nine research projects

GEO 600 and the GEO-HF upgrade program: successes and challenges

The German-British laser-interferometric gravitational wave detector GEO 600 is in its 14th year of operation since its first lock in 2001. After GEO 600 participated in science runs with other first-generation detectors, a program known as GEO-HF began in 2009. The goal was to improve the detector sensitivity at high frequencies, around 1 kHz and above, with technologically advanced yet minimally invasive upgrades. Simultaneously, the detector would record science quality data in between commissioning activities. As of early 2014, all of the planned upgrades have been carried out and sensitivity improvements of up to a factor of four at the high-frequency end of the observation band have been achieved. Besides science data collection, an experimental program is ongoing with the goal to further improve the sensitivity and evaluate future detector technologies. We summarize the results of the GEO-HF program to date and discuss its successes and challenges

Pade approximants for functions with branch points - strong asymptotics of Nuttall-Stahl polynomials

Let f be a germ of an analytic function at infinity that can be analytically continued along any path in the complex plane deprived of a finite set of points, f \in\mathcal{A}(\bar{\C} \setminus A), \sharp A <\infty. J. Nuttall has put forward the important relation between the maximal domain of f where the function has a single-valued branch and the domain of convergence of the diagonal Pade approximants for f. The Pade approximants, which are rational functions and thus single-valued, approximate a holomorphic branch of f in the domain of their convergence. At the same time most of their poles tend to the boundary of the domain of convergence and the support of their limiting distribution models the system of cuts that makes the function f single-valued. Nuttall has conjectured (and proved for many important special cases) that this system of cuts has minimal logarithmic capacity among all other systems converting the function f to a single-valued branch. Thus the domain of convergence corresponds to the maximal (in the sense of minimal boundary) domain of single-valued holomorphy for the analytic function f \in\mathcal{A}(\bar{\C} \setminus A). The complete proof of Nuttall's conjecture (even in a more general setting where the set A has logarithmic capacity zero) was obtained by H. Stahl. In this work, we derive strong asymptotics for the denominators of the diagonal Pade approximants for this problem in a rather general setting. We assume that A is a finite set of branch points of f which have the algebraic character and which are placed in a generic position. The last restriction means that we exclude from our consideration some degenerated "constellations" of the branch points.Comment: 47 pages, 8 figure

Statistical Communication Theory

Contains forward and reports on nine research projects