Die Wirkungsanalyse staatlicher Förderprogramme durch den Einsatz von Matching- und Selektionsmodellen am Beispiel der Fertigungstechnik

Mit dem Ziel die technologische Wettbewerbsfähigkeit zu steigern, investieren die Staaten der OECD jährlich beträchtliche Summen in die Förderung von Forschungs- und Entwicklungsaktivitäten (FuE). Angesichts knapper öffentlicher Budgets ist der Effektivität und Effizienz dieser Förderung eine hohe Bedeutung beizumessen. Neuere Methoden der Wirkungsanalyse tragen dazu bei, begründete Zweifel, die mit dieser Förderung einhergehen, auszuräumen oder zu bekräftigen. Diese Studie widmet sich zwei neueren quantitativen Methoden zur Wirkungsanalyse am Beispiel des deutschen Förderprogramms "Fertigungstechnik". Den Ergebnissen der Selektions- und Matchingansätze zufolge investieren Unternehmen der Fertigungstechnik im Durchschnitt zwischen 67 und 75 Prozent mehr in FuE, wenn sie gefördert werden

Die Wirkungsanalyse staatlicher Förderprogramme durch den Einsatz von Matching- und Selektionsmodellen am Beispiel der Fertigungstechnik

Mit dem Ziel die technologische Wettbewerbsfähigkeit zu steigern, investieren die Staaten der OECD jährlich beträchtliche Summen in die Förderung von Forschungs- und Entwicklungsaktivitäten (FuE). Angesichts knapper öffentlicher Budgets ist der Effektivität und Effizienz dieser Förderung eine hohe Bedeutung beizumessen. Neuere Methoden der Wirkungsanalyse tragen dazu bei, begründete Zweifel, die mit dieser Förderung einhergehen, auszuräumen oder zu bekräftigen. Diese Studie widmet sich zwei neueren quantitativen Methoden zur Wirkungsanalyse am Beispiel des deutschen Förderprogramms ?Fertigungstechnik?. Den Ergebnissen der Selektions- und Matchingansätze zufolge investieren Unternehmen der Fertigungstechnik im Durchschnitt zwischen 67 und 75 Prozent mehr in FuE, wenn sie gefördert werden. --Innovation,Public R&D Subsidies,Policy Evaluation,Parametric and Semiparametric Models

Rapid Bursts of \u3ci\u3eAndrogen-Binding Protein (Abp)\u3c/i\u3e Gene Duplication Occurred Independently in Diverse Mammals

Background The draft mouse (Mus musculus) genome sequence revealed an unexpected proliferation of gene duplicates encoding a family of secretoglobin proteins including the androgen-binding protein (ABP) α, β and γ subunits. Further investigation of 14 α-like (Abpa) and 13 β- or γ-like (Abpbg) undisrupted gene sequences revealed a rich diversity of developmental stage-, sex- and tissue-specific expression. Despite these studies, our understanding of the evolution of this gene family remains incomplete. Questions arise from imperfections in the initial mouse genome assembly and a dearth of information about the gene family structure in other rodents and mammals. Results Here, we interrogate the latest \u27finished\u27 mouse (Mus musculus) genome sequence assembly to show that the Abp gene repertoire is, in fact, twice as large as reported previously, with 30 Abpa and 34 Abpbg genes and pseudogenes. All of these have arisen since the last common ancestor with rat (Rattus norvegicus). We then demonstrate, by sequencing homologs from species within the Mus genus, that this burst of gene duplication occurred very recently, within the past seven million years. Finally, we survey Abp orthologs in genomes from across the mammalian clade and show that bursts of Abp gene duplications are not specific to the murid rodents; they also occurred recently in the lagomorph (rabbit, Oryctolagus cuniculus) and ruminant (cattle, Bos taurus) lineages, although not in other mammalian taxa. Conclusion We conclude that Abp genes have undergone repeated bursts of gene duplication and adaptive sequence diversification driven by these genes\u27 participation in chemosensation and/or sexual identification

ADDA: a domain database with global coverage of the protein universe

We used the Automatic Domain Decomposition Algorithm (ADDA) to generate a database of protein domain families with complete coverage of all protein sequences. Sequences are split into domains and domains are grouped into protein domain families in a completely automated process. The current database contains domains for more than 1.5 million sequences in more than 40 000 domain families. In particular, there are 3828 novel domain families that do not overlap with the curated domain databases Pfam, SCOP and InterPro. The data are freely available for downloading and querying via a web interface (http://ekhidna.biocenter.helsinki.fi:9801/sqgraph/pairsdb)

Revisiting the Flowers-Ruderman instability of magnetic stars

In 1977, Flowers and Ruderman described a perturbation that destabilises a purely dipolar magnetic field in a fluid star. They considered the effect of cutting the star in half along a plane containing the symmetry axis and rotating each half by 90\degr in opposite directions, which would cause the energy of the magnetic field in the exterior of the star to be greatly reduced, just as it happens with a pair of aligned magnets. We formally solve for the energy of the external magnetic field and check that it decreases monotonously along the entire rotation. We also describe the instability using perturbation theory, and see that it happens due to the work done by the interaction of the magnetic field with surface currents. Finally, we consider the stabilising effect of adding a toroidal field by studying the potential energy perturbation when the rotation is not done along a sharp cut, but with a continuous displacement field that switches the direction of rotation across a region of small but finite width. Using these results, we estimate the relative strengths of the toroidal and poloidal field needed to make the star stable to this displacement and see that the energy of the toroidal field required for stabilisation is much smaller than the energy of the poloidal field. We also show that, contrary to a common argument, the Flowers-Ruderman instability cannot be applied many times in a row to reduce the external magnetic energy indefinitely.Comment: Uploaded complete version with corrections from the MNRAS refere

Rapid bursts of androgen-binding protein (Abp) gene duplication occurred independently in diverse mammals

<p>Abstract</p> <p>Background</p> <p>The draft mouse (<it>Mus musculus</it>) genome sequence revealed an unexpected proliferation of gene duplicates encoding a family of secretoglobin proteins including the androgen-binding protein (ABP) α, β and γ subunits. Further investigation of 14 α-like (<it>Abpa</it>) and 13 β- or γ-like (<it>Abpbg</it>) undisrupted gene sequences revealed a rich diversity of developmental stage-, sex- and tissue-specific expression. Despite these studies, our understanding of the evolution of this gene family remains incomplete. Questions arise from imperfections in the initial mouse genome assembly and a dearth of information about the gene family structure in other rodents and mammals.</p> <p>Results</p> <p>Here, we interrogate the latest 'finished' mouse (<it>Mus musculus</it>) genome sequence assembly to show that the <it>Abp </it>gene repertoire is, in fact, twice as large as reported previously, with 30 <it>Abpa </it>and 34 <it>Abpbg </it>genes and pseudogenes. All of these have arisen since the last common ancestor with rat (<it>Rattus norvegicus</it>). We then demonstrate, by sequencing homologs from species within the <it>Mus </it>genus, that this burst of gene duplication occurred very recently, within the past seven million years. Finally, we survey <it>Abp </it>orthologs in genomes from across the mammalian clade and show that bursts of <it>Abp </it>gene duplications are not specific to the murid rodents; they also occurred recently in the lagomorph (rabbit, <it>Oryctolagus cuniculus</it>) and ruminant (cattle, <it>Bos taurus</it>) lineages, although not in other mammalian taxa.</p> <p>Conclusion</p> <p>We conclude that <it>Abp </it>genes have undergone repeated bursts of gene duplication and adaptive sequence diversification driven by these genes' participation in chemosensation and/or sexual identification.</p

Microscale <i>In Vitro</i> Assays for the Investigation of Neutral Red Retention and Ethoxyresorufin-<i>O</i>-Deethylase of Biofuels and Fossil Fuels

<div><p>Only few information on the potential toxic effectiveness of biofuels are available. Due to increasing worldwide demand for energy and fuels during the past decades, biofuels are considered as a promising alternative for fossil fuels in the transport sector. Hence, more information on their hazard potentials are required to understand the toxicological impact of biofuels on the environment. In the German Cluster of Excellence “Tailor-made Fuels from Biomass” design processes for economical, sustainable and environmentally friendly biofuels are investigated. In an unique and interdisciplinary approach, ecotoxicological methods are applied to gain information on potential adverse environmental effects of biofuels at an early phase of their development. In the present study, three potential biofuels, ethyl levulinate, 2-methyltetrahydrofuran and 2-methylfuran were tested. Furthermore, we investigated a fossil gasoline fuel, a fossil diesel fuel and an established biodiesel. Two <i>in vitro</i> bioassays, one for assessing cytotoxicity and one for aryl hydrocarbon receptor agonism, so called dioxin-like activity, as measured by Ethoxyresorufin-<i>O</i>-Deethylase, were applied using the permanent fish liver cell line RTL-W1 (<i>Oncorhynchus mykiss</i>). The special properties of these fuel samples required modifications of the test design. Points that had to be addressed were high substance volatility, material compatibility and low solubility. For testing of gasoline, diesel and biodiesel, water accommodated fractions and a passive dosing approach were tested to address the high hydrophobicity and low solubility of these complex mixtures. Further work has to focus on an improvement of the chemical analyses of the fuel samples to allow a better comparison of any effects of fossil fuels and biofuels.</p></div

Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy

&lt;b&gt;Background:&lt;/b&gt; Androgen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2–3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objective:&lt;/b&gt; To undertake quantitative tumour transcriptome profiling prior to and following ADT to identify functionally important androgen-regulated pathways or genes that may be reactivated in CRPC.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Design, setting, and participants:&lt;/b&gt; RNA sequencing (RNA-seq) was performed on tumour-rich, targeted prostatic biopsies from seven patients with locally advanced or metastatic PCa before and approximately 22 wk after ADT initiation. Differentially regulated genes were identified in treatment pairs and further investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on cell lines and immunohistochemistry on a separate CRPC patient cohort. Functional assays were used to determine the effect of pathway modulation on cell phenotypes.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Outcome measurements and statistical analysis:&lt;/b&gt; We searched for gene expression changes affecting key cell signalling pathways that may be targeted as proof of principle in a CRPC in vitro cell line model.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results and limitations:&lt;/b&gt; We identified ADT-regulated signalling pathways, including the Wnt/β-catenin signalling pathway, and observed overexpression of β-catenin in a subset of CRPC by immunohistochemistry. We validated 6 of 12 (50%) pathway members by qRT-PCR on LNCaP/LNCaP-AI cell RNAs, of which 4 (67%) demonstrated expression changes consistent with RNA-seq data. We show that the tankyrase inhibitor XAV939 (which promotes β-catenin degradation) reduced androgen-independent LNCaP-AI cell line growth compared with androgen-responsive LNCaP cells via an accumulation of cell proportions in the G0/G1 phase and reduction in the S and G2/M phases. Our biopsy protocol did not account for tumour heterogeneity, and pathway inhibition was limited to pharmacologic approaches.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions:&lt;/b&gt; RNA-seq of paired PCa samples revealed ADT-regulated signalling pathways. Proof-of-principle inhibition of the Wnt/β-catenin signalling pathway specifically delays androgen-independent PCa cell cycle progression and proliferation and warrants further investigation as a potential target for therapy for CRPC.&lt;p&gt;&lt;/p&gt

Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations.

BACKGROUND: Early life exposure to adverse environments affects cardiovascular and metabolic systems in the offspring. These programmed effects are transmissible to a second generation through both male and female lines, suggesting germline transmission. We have previously shown that prenatal overexposure to the synthetic glucocorticoid dexamethasone (Dex) in rats reduces birth weight in the first generation (F1), a phenotype which is transmitted to a second generation (F2), particularly through the male line. We hypothesize that Dex exposure affects developing germ cells, resulting in transmissible alterations in DNA methylation, histone marks and/or small RNA in the male germline. RESULTS: We profile epigenetic marks in sperm from F1 Sprague Dawley rats expressing a germ cell-specific GFP transgene following Dex or vehicle treatment of the mothers, using methylated DNA immunoprecipitation sequencing, small RNA sequencing and chromatin immunoprecipitation sequencing for H3K4me3, H3K4me1, H3K27me3 and H3K9me3. Although effects on birth weight are transmitted to the F2 generation through the male line, no differences in DNA methylation, histone modifications or small RNA were detected between germ cells and sperm from Dex-exposed animals and controls. CONCLUSIONS: Although the phenotype is transmitted to a second generation, we are unable to detect specific changes in DNA methylation, common histone modifications or small RNA profiles in sperm. Dex exposure is associated with more variable 5mC levels, particularly at non-promoter loci. Although this could be one mechanism contributing to the observed phenotype, other germline epigenetic modifications or non-epigenetic mechanisms may be responsible for the transmission of programmed effects across generations in this model