How should novelty be valued in science?

<p>Box plot analysis of serum concentrations of sRAGE (A), esRAGE (B), S100A9 (C) and HMGB1 (D) in patients with CTEPH (n = 26) and controls (n = 33). Independent Student’s t-test was used to compare groups. <i>RAGE</i> receptor for advanced glycation endproducts, <i>sRAGE</i> soluble RAGE, <i>esRAGE</i> endogenous secretory RAGE, <i>S100A9</i> member of S100 family of Ca+ binding proteins, <i>HMGB1</i> high mobility group box1, <i>CTEPH</i> chronic thromboembolic pulmonary hypertension.</p

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Intergenerational continuity in attitudes toward reading and reading behavior

Students' reading preferences develop in social contexts, and parents shape such environments. Assuming a process of transmission across generations, we analyzed the role of mothers' attitudes toward reading and reading behavior. A sample of 380 ninth-grade students completed a questionnaire to assess their attitudes toward reading (with respect to utility and enjoyment) and to collect details about their extracurricular reading behavior. Mothers were interviewed and asked to provide comparable information about their own reading behavior and attitudes. Results showed substantial positive relations between mothers' and students' attitudes toward reading and reading behavior, although the effects were small in magnitude. Taken together, evenwhen children reach adolescence, socialization effects from parents can be found in the domain of reading

Dielektrischer Elastomeraktor und Verfahren zu seiner Herstellung

The invention relates to dielectric elastomer actuators (DEA) and a production method for such elastomer actuators. According to the invention, an elastically deformable dielectric polymer film (1) is enclosed on two opposite surfaces by two elastically deformable electrodes. The electrodes are formed from a polymer in which electrically conductive particles, particularly carbon nanotubes, are embedded in a proportion at which the percolation threshold is overcome. The electrodes are connected to the dielectric film by a material bond, whereby structuring having recesses (2) is formed on at least one of the surfaces of the dielectric film on which an electrode is formed

Evaluation of mechanical and laser surface pre-treatments on the strength of adhesive bonded steel joints for the automotive industry

Recent research efforts in the automotive industry have been focused on the integration of high-strength steels within lightweight vehicles by using improved joining techniques. The present work falls in this subject area and is focused on the analysis of adhesive bonded dual-phase steel/epoxy joints for the automotive industry. Two quasi-static loadcases were considered, i.e. single-lap and T-peel tests, and various surface preparation strategies were evaluated. In particular, the mating surfaces were pre-treated by using pulsed laser irradiation with a fiber laser (1064 nm) and comparisons were made with degreasing and sand blasting. Moreover, the effects of bondline thickness and adhesive type were also assessed. To this aim, two epoxy adhesives with fairly different mechanical behavior (i.e. strain hardening versus elasto-plastic) were deployed for joints fabrication. Finally, T-peel tests were also carried out after sample cycling under controlled high humidity and temperature (i.e. accelerated aging). The obtained results highlighted the beneficial effect of laser irradiation on the joints’ mechanical behavior under both static and hydrothermal loadings

A Person Centered Approach for Analyzing the Development of Students’ Subject-Interests in Language Arts, Mathematics, and English as a Foreign Language From Grade 4 to 11

Forschungsarbeiten zur Interessensentwicklung konnten vielfach zeigen, dass Schülerinnen und Schüler mit undifferenziert hohen schulfachbezogenen Interessen in die Schule eintreten, die mittleren Interessen im weiteren Schulverlauf jedoch stetig absinken. Neuere Studien verweisen auf einen stagnierenden Interessensabfall ab Jahrgangsstufe 7 und einen leichten Interessensanstieg etwa ab Jahrgangsstufe 11. Gemäß dem Modell der Interessensdifferenzierung (Todt & Schreiber, 1998) lässt sich der mittlere Interessensabfall auf einen Differenzierungsprozess zurückführen: Die Schülerinnen und Schüler fokussieren ihr Interesse nach Schuleintritt auf einige wenige Fächer, während die übrigen Fachinteressen sinken. Anhand der Fachinteressen Deutsch, Mathematik und Englisch zu Jahrgangsstufe 4 bis 11 wurde untersucht, inwieweit sich derartige Differenzierungsprozesse über eine latente Klassenanalyse mit längsschnittlichen Daten (LCA) nachzeichnen lassen. Die Analyse von N = 293 Schülerinnen und Schülern bestätigte zunächst den Befund einer mittleren, kurvenlinearen Interessensentwicklung. Die LCA ergab fünf latente Klassen. Die Mittelwertdifferenzen der Fachinteressen ließen nur für zwei der fünf latenten Klassen eine zunehmende Interessensdifferenzierung zu Jahrgangsstufe 11 vermuten.Numerous studies showed that students enter the school system with high and undifferentiated interests. However, academic interests on average decrease during the school course. Recent findings point to a stagnancy of this negative development in grade 7 and a slight increase in grade 11. According to the model of interest differentiation (Todt & Schreiber, 1998) students’ decreasing academic interests can be traced back to a process of differentiation: Students focus their interests on a limited number of subjects whereas their interests for the remaining subjects decrease. Using students’ self-reports on their subject-interests in language arts, mathematics and English as a foreign language at grade 4 to grade 11 we analyzed whether (a) latent class(es) (latent class analysis with longitudinal data, LCA) of a differentiating interest profile can be found. On average the analysis of N = 293 students showed decreasing interests up to grade 7 and slightly increasing interests in grade 11. The LCA indicated five latent classes. Two of them revealed a pattern of interest differentiation in grade 11

Enhancement of static strength and long term durability of steel/epoxy joints through a fiber laser surface pre-treatment

The aim of this work is to investigate the effectiveness of laser irradiation on steel substrates for adhesive bonding. The evolution of surface topography and wettability for various pulse fluencies was investigated. The most suitable processing conditions were then selected and adhesive bonded steel/epoxy single-lap and T-peel joints were prepared for static testing. Moreover, in order to assess joint strength against environmental attack, an additional batch of samples was subjected to hydrothermal cycling before testing. The obtained results were compared with baseline samples fabricated using degreasing and sand blasting surface pre-treatments. Post-failure SEM analyses of fracture surfaces were undertaken to survey the locus of failure within the joint bond-line. Results indicated that laser irradiation effectively enhances the overall mechanical behavior of the joint under shear and peel loading. In addition, it allows to retain joint strength after exposure to aggressive environmental conditions