Leitfaden für Beratungsgespräche im Forschungsdatenmanagement

Das Dokument beschreibt Erfahrungen, die im Rahmen von Beratungsgesprächen mit Forschergruppen an der TU Dresden zum Thema Forschungsdatenmanagement (FDM) gemacht worden sind. Im Zentrum der Beratungsleistung steht dabei zunächst die Erfassung des FDM-Ist-Zustands einer Forschergruppe. Dazu wird gemeinsam ein Datenflussdiagramm erstellt, das die folgende Frage beantwortet: Welche Daten werden wie, von wem und zu welchem Zweck erhoben? Auf Basis dieses Datenflussdiagramms werden anschließend in einem mehrstufigen Beratungs- und Implementierungsprozess Lösungen für den FDM-Soll-Zustand angeboten

Deltoid muscular flap transfer for the treatment of irreparable rotator cuff tears

The purpose of this study was to evaluate the outcome of deltoid muscle flap transfer for the treatment of irreparable rotator cuff tears. In a retrospective study 20 consecutive patients were evaluated. The index procedure took place between 2000 and 2003. Fifteen patients were male, mean age was 62 years. Inclusion criterion was a rotator cuff defect Bateman grade IV. Exclusion criteria were smaller defects, shoulder instability and fractures of the injured shoulder. An open reconstruction with acromioplasty and a pedicled delta flap was performed. Follow up period was mean 42 months. Follow-up included clinical examination, Magnetic Resonance Imaging (MRI) and the Constant and Simple (CS) shoulder tests. According to the Constant shoulder test the results were good in 13 patients, fair in 5 and unsatisfactory in 2. The pre-operative Constant Score improved from mean 25.7 points (±5.3) to 72.3 (±7.8) at follow-up. The mean values for the subcategories of CS increased significantly from 3.9 to 14.4 points for pain and from 4.2 to 15.9 points for activities daily routine (p<0.05). The change in range of motion and strength were not significant (p>0.05). Results of the Simple Shoulder Test showed a significant increase of the mean values from pre-operative 4.3 to 14.7 points post-operatively. MRI showed a subacromial covering of the defect in all cases, all flaps where intact on MRI but always the flap showed marked fatty degeneration. In conclusion, the delta flap is a simple method for the repair of large defects of the rotator cuff leading to satisfying medium results

Differential Interactions of the Catalytic Subunits of Adenylyl Cyclase with Forskolin Analogs

The diterpene forskolin (FS) binds to, and activates, mammalian membranous adenylyl cyclase (AC) isoforms I–VIII. Diterpenes without C1-OH group do not activate ACs. The C1-OH group forms a hydrogen bond with the backbone oxygen of Val506 of the C1 catalytic subunit of AC (isoform V numbering). To better understand the mechanism of AC activation we examined the interactions of FS and eight FS analogs with purified catalytic AC subunits C1 (AC V) and C2 (AC II) by fluorescence spectroscopy, using 2′,3′-O-(N-methylanthraniloyl)-guanosine 5′-triphosphate (MANT-GTP) as fluorescent reporter probe, and by enzymatic activity. FS analogs induced C1/C2 assembly as assessed by fluorescence resonance energy transfer from Trp1020 of C2 to MANT-GTP and by increased direct MANT-GTP fluorescence in the order of efficacy FS ~ 7-deacetyl-FS ~ 6-acetyl-7-deacetyl-FS ~ 9-deoxy-FS > 7-deacetyl-7-(N-methylpiperazino-γ-butyryloxy)-FS > 1-deoxy-FS ~ 1,9-dideoxy-FS ~ 7-deacetyl-1-deoxy-FS ~ 7-deacetyl-1,9-dideoxy-FS. In contrast, FS analogs activated catalysis in the order of efficacy FS > 7-deacety-FS ~ 6-acetyl-7-deacetyl-FS ~ 9-deoxy-FS > 7-deacetyl-7-(N-methylpiperazino-γ-butyryloxy)-FS ≫ 1-deoxy-FS, 1,9-dideoxy-FS, 7-deacetyl-1-deoxy-FS and 7-deacetyl-1,9-dideoxy-FS (all ineffective). 1-Deoxy-FS analogs inhibited FS-stimulated catalysis by an apparently non-competitive mechanism. Our data suggest a two-step mechanism of AC activation by diterpenes. In the first step, diterpenes, regardless of their substitution pattern, promote C1/C2 assembly. In the second and yet poorly understood step, diterpenes that form a hydrogen bond between C1-OH and Val506 promote a conformational switch that results in activation of catalysis. The apparent non-competitive interaction of FS with 1-deoxy-FS analogs is explained by impaired ligand exchange due to strong hydrophobic interactions with C1/C2

Synthesis and characterization of tantalum(V) boronate clusters : multifunctional Lewis acid cages for binding guests

Open and shut cases: Tantalum(V) boronate clusters [(Cp*Ta)3(μ2‐η2‐RBO2)3(μ2‐O)2(μ2‐OH)(μ3‐OH)] (Cp*=η5‐C5Me5; 1: R=Ph, 2: R=iBu) with Lewis acidic cavities were prepared. Whereas the cavity of 2 is blocked by the iBu groups, that of 1 is open and can bind Lewis basic guests such as ketones (see picture) by interaction with one boronate and one μ3‐OH ligand

Differential Inhibition of Various Adenylyl Cyclase Isoforms and Soluble Guanylyl Cyclase by 2\u27,3\u27-O-(2,4,6-Trinitrophenyl)-Substituted Nucleoside 5\u27-Triphosphates

Adenylyl cyclases (ACs) catalyze the conversion of ATP into the second messenger cAMP and play a key role in signal transduction. In a recent study (Mol Pharmacol 70: 878-886, 2006), we reported that 2\u27,3\u27-O-(2,4,6-trinitrophenyl)-substituted nucleoside 5\u27-triphosphates (TNP-NTPs) are potent inhibitors (K(i) values in the 10 nM range) of the purified catalytic subunits VC1 and IIC2 of membranous AC (mAC). The crystal structure of VC1: IIC2 in complex with TNP-ATP revealed that the nucleotide binds to the catalytic site with the TNP-group projecting into a hydrophobic pocket. The aims of this study were to analyze the interaction of TNP-nucleotides with VC1: IIC2 by fluorescence spectroscopy and to analyze inhibition of mAC isoforms, soluble AC (sAC), soluble guanylyl cyclase (sGC), and G-proteins by TNP-nucleotides. Interaction of VC1: IIC2 with TNP-NDPs and TNP-NTPs resulted in large fluorescence increases that were differentially reduced by a water-soluble forskolin analog. TNP-ATP turned out to be the most potent inhibitor for ACV (K(i), 3.7 nM) and sGC (K(i), 7.3 nM). TNP-UTP was identified as the most potent inhibitor for ACI (K(i), 7.1 nM) and ACII (K(i), 24 nM). TNP-NTPs inhibited sAC and GTP hydrolysis by G(s)- and G(i)-proteins only with low potencies. Molecular modeling revealed that TNP-GTP and TNP-ATP interact very similarly, but not identically, with VC1: IIC2. Collectively, our data show that TNP-nucleotides are useful fluorescent probes to monitor conformational changes in VC1: IIC2 and that TNP-NTPs are a promising starting point to develop isoform-selective AC and sGC inhibitors. TNP-ATP is the most potent sGC inhibitor known so far

Impact of Monetary Uncertainty and Economic Uncertainty on Money Demand in Africa

This dissertation investigates the role that economic uncertainties and monetary uncertainties play in the money demand function for 21 African countries. The Auto-regressive Distributive Lag (ARDL) and F-test approach are employed using quarterly time series data covering the period from 1971I-2012IV. In particular, this paper aims to demonstrate both short and long-run relationships between the dependent variables, Real Money Aggregate (M2), and the independent variables that include real income (Y), inflation rate nominal effective exchange rate (NEX), output uncertainty (VY), and monetary uncertainty (VM). We apply GARCH methodology to approximate the uncertainty measures. The empirical results show that except for Egypt, monetary VM and VY have significant short-run as well as long-run effects on money demand in all the countries, with some variables carrying negative or positive coefficient. We find that the coefficients of Y in all the countries is positive while that of and NEX are negative, implying depreciation of domestic currency decreases demand for money. The results also indicate that CUSUM and CUSUMSQ test are stable, thus M2 is stable in all the countries except Egyp

Sepsis related mortality of extremely low gestational age newborns after the introduction of colonization screening for multi-drug resistant organisms

Background: In 2013 German infection surveillance guidelines recommended weekly colonization screening for multidrug-resistant (MDRO) or highly epidemic organisms for neonatal intensive care units (NICUs) and extended hygiene measures based on screening results. It remains a matter of debate whether screening is worth the effort. We therefore aimed to evaluate sepsis related outcomes before and after the guideline update. Methods: The German Neonatal Network (GNN) is a prospective cohort study including data from extremely preterm infants between 22 + 0 and 28 + 6 gestational weeks born in 62 German level III NICUs. Results: Infants treated after guideline update (n = 8.903) had a lower mortality (12.5% vs. 13.8%, p = 0.036), reduced rates for clinical sepsis (31.4 vs. 42.8%, p < 0.001) and culture-proven sepsis (14.4% vs. 16.5%, p = 0.003) as compared to infants treated before update (n = 3.920). In a multivariate logistic regression analysis, nine pathogens of cultureproven sepsis were associated with sepsis-related death, e.g. Pseudomonas aeruginosa [OR 59 (19–180), p < 0.001)]. However, the guideline update had no significant effect on pathogen-specific case fatality, total sepsis-related mortality and culture-proven sepsis rates with MDRO. While the exposure of GNN infants to cefotaxime declined over time (31.1 vs. 40.1%, p < 0.001), the treatment rate with meropenem was increased (31.6 vs. 26.3%, p < 0.001). Conclusions: The introduction of weekly screening and extended hygiene measures is associated with reduced sepsis rates, but has no effects on sepsis-related mortality and sepsis with screening-relevant pathogens. The high exposure rate to meropenem should be a target of antibiotic stewardship programs

HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology

We present HepatoNet1, a manually curated large-scale metabolic network of the human hepatocyte that encompasses >2500 reactions in six intracellular and two extracellular compartments.Using constraint-based modeling techniques, the network has been validated to replicate numerous metabolic functions of hepatocytes corresponding to a reference set of diverse physiological liver functions.Taking the detoxification of ammonia and the formation of bile acids as examples, we show how these liver-specific metabolic objectives can be achieved by the variable interplay of various metabolic pathways under varying conditions of nutrients and oxygen availability

Dimer formation and conformational flexibility ensure cytoplasmic stability and nuclear accumulation of Elk-1

The ETS (E26) protein Elk-1 serves as a paradigm for mitogen-responsive transcription factors. It is multiply phosphorylated by mitogen-activated protein kinases (MAPKs), which it recruits into pre-initiation complexes on target gene promoters. However, events preparatory to Elk-1 phosphorylation are less well understood. Here, we identify two novel, functional elements in Elk-1 that determine its stability and nuclear accumulation. One element corresponds to a dimerization interface in the ETS domain and the second is a cryptic degron adjacent to the serum response factor (SRF)-interaction domain that marks dimerization-defective Elk-1 for rapid degradation by the ubiquitin–proteasome system. Dimerization appears to be crucial for Elk-1 stability only in the cytoplasm, as latent Elk-1 accumulates in the nucleus and interacts dynamically with DNA as a monomer. These findings define a novel role for the ETS domain of Elk-1 and demonstrate that nuclear accumulation of Elk-1 involves conformational flexibility prior to its phosphorylation by MAPKs