TY - JOUR A1 - Blättner, Sebastian A1 - Das, Sudip A1 - Paprotka, Kerstin A1 - Eilers, Ursula A1 - Krischke, Markus A1 - Kretschmer, Dorothee A1 - Remmele, Christian W. A1 - Dittrich, Marcus A1 - Müller, Tobias A1 - Schuelein-Voelk, Christina A1 - Hertlein, Tobias A1 - Mueller, Martin J. A1 - Huettel, Bruno A1 - Reinhardt, Richard A1 - Ohlsen, Knut A1 - Rudel, Thomas A1 - Fraunholz, Martin J. T1 - Staphylococcus aureus Exploits a Non-ribosomal Cyclic Dipeptide to Modulate Survival within Epithelial Cells and Phagocytes JF - PLoS Pathogens N2 - Community-acquired (CA) Staphylococcus aureus cause various diseases even in healthy individuals. Enhanced virulence of CA-strains is partly attributed to increased production of toxins such as phenol-soluble modulins (PSM). The pathogen is internalized efficiently by mammalian host cells and intracellular S. aureus has recently been shown to contribute to disease. Upon internalization, cytotoxic S. aureus strains can disrupt phagosomal membranes and kill host cells in a PSM-dependent manner. However, PSM are not sufficient for these processes. Here we screened for factors required for intracellular S. aureus virulence. We infected escape reporter host cells with strains from an established transposon mutant library and detected phagosomal escape rates using automated microscopy. We thereby, among other factors, identified a non-ribosomal peptide synthetase (NRPS) to be required for efficient phagosomal escape and intracellular survival of S. aureus as well as induction of host cell death. By genetic complementation as well as supplementation with the synthetic NRPS product, the cyclic dipeptide phevalin, wild-type phenotypes were restored. We further demonstrate that the NRPS is contributing to virulence in a mouse pneumonia model. Together, our data illustrate a hitherto unrecognized function of the S. aureus NRPS and its dipeptide product during S. aureus infection. KW - cell death KW - cytotoxicity KW - Staphylococcus aureus KW - host cells KW - neutrophils KW - macrophages KW - transposable elements KW - epithelial cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180380 VL - 12 IS - 9 ER - TY - JOUR A1 - Zahnert, Thomas A1 - Löwenheim, Hubert A1 - Beutner, Dirk A1 - Hagen, Rudolf A1 - Ernst, Arneborg A1 - Pau, Hans-Wilhelm A1 - Zehlicke, Thorsten A1 - Kühne, Hilke A1 - Friese, Natascha A1 - Tropitzsch, Anke A1 - Lüers, Jan-Christoffer A1 - Mlynski, Robert A1 - Todt, Ingo A1 - Hüttenbrink, Karl-Bernd T1 - Multicenter Clinical Trial of Vibroplasty Couplers to Treat Mixed/Conductive Hearing Loss: First Results JF - Audiology and Neurotology N2 - Objective: To evaluate the safety and effectiveness of round window (RW), oval window (OW), CliP and Bell couplers for use with an active middle ear implant. Methods: This is a multicenter, long-term, prospective trial with consecutive enrollment, involving 6 university hospitals in Germany. Bone conduction, air conduction, implant-aided warble-tone thresholds and Freiburger monosyllable word recognition scores were compared with unaided preimplantation results in 28 moderate-to-profound hearing-impaired patients after 12 months of follow-up. All patients had previously undergone failed reconstruction surgeries (up to 5 or more). In a subset of patients, additional speech tests at 12 months postoperatively were used to compare the aided with the unaided condition after implantation with the processor switched off. An established quality-of-life questionnaire for hearing aids was used to determine patient satisfaction. Results: Postoperative bone conduction remained stable. Mean functional gain for all couplers was 37 dB HL (RW = 42 dB, OW = 35 dB, Bell = 38 dB, CliP = 27 dB). The mean postoperative Freiburger monosyllable score was 71% at 65 dB SPL. The postimplantation mean SRT50 (speech reception in quiet for 50% understanding of words in sentences) improved on average by 23 dB over unaided testing and signal-to-noise ratios also improved in all patients. The International Outcome Inventory for Hearing Aids (IOI-HA)quality-of-life questionnaire was scored very positively by all patients. Conclusion: A significant improvement was seen with all couplers, and patients were satisfied with the device at 12 months postoperatively. These results demonstrate that an active implant is an advantage in achieving good hearing benefit in patients with prior failed reconstruction surgery. KW - conductive hearing loss KW - mixed hearing loss KW - vibroplasty KW - couplers KW - middle ear implant Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199129 SN - 1420-3030 SN - 1421-9700 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 21 IS - 4 ER - TY - JOUR A1 - Schmid, Michael A1 - Steinlein, Claus A1 - Winking, Heinz T1 - Multicolor Spectral Analyses of Mitotic and Meiotic Mouse Chromosomes Involved in Multiple Robertsonian Translocations. I. The CD/Cremona Hybrid Strain JF - Cytogenetic and Genome Research N2 - Multicolor spectral analysis (spectral karyotyping) was applied to mitotic and male diakinetic chromosomes of hybrid mice carrying a unique system of 18 autosomal Robertsonian translocation chromosomes with alternating arm homologies. Only the autosomes 19 and the XY sex chromosomes are excluded from these Robertsonian translocations. The translocations, previously identified by conventional banding analyses, could be verified by spectral karyotyping. Besides the Robertsonian translocations, no other interchromosomal rearrangements were detected. In diakineses of male meiosis, the 18 metacentric Robertsonian translocation chromosomes form a very large meiotic ‘superring'. The predictable, specific order of the chromosomes along this ‘superring' was completely confirmed by multicolor spectral analysis. In the majority of diakineses analyzed, the free autosomal bivalent 19 and the XY sex bivalent form a conspicuous complex which tightly associates with the 12;14 Robertsonian translocation chromosome in the ‘superring'. KW - meiotic ‘superring’ KW - mouse KW - Robertsonian translocation chromosomes KW - spectral karyotyping Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199013 SN - 1424-8581 SN - 1424-859X N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 147 IS - 4 ER - TY - JOUR A1 - Schmid, Michael A1 - Steinlein, Claus T1 - Chromosome Banding in Amphibia. XXXIII. Demonstration of 5-Methylcytosine-Rich Heterochromatin in Anura JF - Cytogenetic and Genome Research N2 - An experimental approach using monoclonal anti-5-methylcytosine (5-MeC) antibodies and indirect immunofluorescence was elaborated for detecting 5-MeC-rich chromosome regions in anuran chromosomes. This technique was applied to mitotic metaphases of 6 neotropical frog species belonging to 6 genera and 4 families. The hypermethylation patterns were compared with a variety of banding patterns obtained by conventional banding techniques. The hypermethylated DNA sequences are species-specific and located exclusively in constitutive heterochromatin. They are found in centromeric, pericentromeric, telomeric, and interstitial positions of the chromosomes and adjacent to nucleolus organizer regions. 5-MeC-rich DNA sequences can be embedded both in AT- and GC-rich repetitive DNA. The experimental parameters that have major influence on the reproducibility and quality of the anti-5-MeC antibody labeling are discussed. KW - Anura KW - heterochromatin KW - hypermethylated DNA KW - immunofluorescence KW - 5-Methylcytosine Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199022 SN - 1424-8581 SN - 1424-859X N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 148 IS - 1 ER - TY - JOUR A1 - Dengler, Julius A1 - Maldaner, Nicolai A1 - Gläsker, Sven A1 - Endres, Matthias A1 - Wagner, Martin A1 - Malzahn, Uwe A1 - Heuschmann, Peter U. A1 - Vajkoczy, Peter T1 - Outcome of Surgical or Endovascular Treatment of Giant Intracranial Aneurysms, with Emphasis on Age, Aneurysm Location, and Unruptured Aneuryms - A Systematic Review and Meta-Analysis JF - Cerebrovascular Diseases N2 - Background: Designing treatment strategies for unruptured giant intracranial aneurysms (GIA) is difficult as evidence of large clinical trials is lacking. We examined the outcome following surgical or endovascular GIA treatment focusing on patient age, GIA location and unruptured GIA. Methods: Medline and Embase were searched for studies reporting on GIA treatment outcome published after January 2000. We calculated the proportion of good outcome (PGO) for all included GIA and for unruptured GIA by meta-analysis using a random effects model. Results: We included 54 studies containing 64 study populations with 1,269 GIA at a median follow-up time (FU-T) of 26.4 months (95% CI 10.8-42.0). PGO was 80.9% (77.4-84.4) in the analysis of all GIA compared to 81.2% (75.3-86.1) in the separate analysis of unruptured GIA. For each year added to patient age, PGO decreased by 0.8%, both for all GIA and unruptured GIA. For all GIA, surgical treatment resulted in a PGO of 80.3% (95% CI 76.0-84.6) compared to 84.2% (78.5-89.8, p = 0.27) after endovascular treatment. In unruptured GIA, PGO was 79.7% (95% CI 71.5-87.8) after surgical treatment and 84.9% (79.1-90.7, p = 0.54) after endovascular treatment. PGO was lower in high quality studies and in studies presenting aggregate instead of individual patient data. In unruptured GIA, the OR for good treatment outcome was 5.2 (95% CI 2.0-13.0) at the internal carotid artery compared to 0.1 (0.1-0.3, p < 0.1) in the posterior circulation. Patient sex, FU-T and prevalence of ruptured GIA were not associated with PGO. Conclusions: We found that the chances of good outcome after surgical or endovascular GIA treatment mainly depend on patient age and aneurysm location rather than on the type of treatment conducted. Our analysis may inform future research on GIA. KW - surgical aneurysm treatment KW - giant intracranial aneurysm KW - endovascular treatment Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196792 SN - 1015-9770 SN - 1421-9786 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 41 IS - 3-4 ER - TY - JOUR A1 - Almanzar, Giovanni A1 - Klein, Matthias A1 - Schmalzing, Marc A1 - Hilligardt, Deborah A1 - El Hajj, Nady A1 - Kneitz, Hermann A1 - Wild, Vanessa A1 - Rosenwald, Andreas A1 - Benoit, Sandrine A1 - Hamm, Henning A1 - Tony, Hans-Peter A1 - Haaf, Thomas A1 - Goebeler, Matthias A1 - Prelog, Martina T1 - Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis JF - International Archives of Allergy and Immunology N2 - Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity. Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype. KW - methylation KW - systemic sclerosis KW - suppression KW - Tregs KW - Th17 Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196577 SN - 1018-2438 SN - 1423-0097 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 171 IS - 2 ER - TY - JOUR A1 - Schmid, Michael A1 - Steinlein, Claus T1 - Chromosome Banding in Amphibia. XXXIV. Intrachromosomal Telomeric DNA Sequences in Anura JF - Cytogenetic and Genome Research N2 - The mitotic chromosomes of 4 anuran species were examined by various classical banding techniques and by fluorescence in situ hybridization using a (TTAGGG)\(_n\) repeat. Large intrachromosomal telomeric sequences (ITSs) were demonstrated in differing numbers and chromosome locations. A detailed comparison of the present results with numerous published and unpublished data allowed a consistent classification of the various categories of large ITSs present in the genomes of anurans and other vertebrates. The classification takes into consideration the total numbers of large ITSs in the karyotypes, their chromosomal locations and their specific distribution patterns. A new category of large ITSs was recognized to exist in anuran species. It consists of large clusters of ITSs located in euchromatic chromosome segments, which is in clear contrast to the large ITSs in heterochromatic chromosome regions known in vertebrates. The origin of the different categories of large ITSs in heterochromatic and euchromatic chromosome regions, their mode of distribution in the karyotypes and evolutionary fixation in the genomes, as well as their cytological detection are discussed. KW - heterochromatin KW - intrachromosomal telomeric sequences KW - Anura KW - euchromatin KW - evolutionary fixation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196693 SN - 1424-8581 SN - 1424-859X N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 148 IS - 2-3 ER - TY - JOUR A1 - Schmid, Michael A1 - Steinlein, Claus A1 - Lomb, Christian A1 - Sperling, Karl A1 - Neitzel, Heidemarie T1 - 5-Methylcytosine-Rich Heterochromatin in the Indian Muntjac JF - Cytogenetic and Genome Research N2 - Two 5-methylcytosine (5-MeC)-rich heterochromatic regions were demonstrated in metaphase chromosomes of the Indian muntjac by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. The metaphases were obtained from diploid and triploid cell lines. A major region is located in the ‘neck' of the 3;X fusion chromosome and can be detected after denaturation of the chromosomal DNA with UV-light irradiation for 1 h. It is located exactly at the border of the X chromosome and the translocated autosome 3. A minor region is found in the centromeric region of the free autosome 3 after denaturing the chromosomal DNA for 3 h or longer. The structure and possible function of the major hypermethylated region as barrier against spreading of the X-inactivation process into the autosome 3 is discussed. KW - heterochromatin KW - immunofluorescence KW - Indian muntjac KW - 5-Methylcytosine Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196701 SN - 1424-8581 SN - 1424-859X N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 147 IS - 4 ER - TY - JOUR A1 - Schmid, Michael A1 - Steinlein, Claus A1 - Yano, Cassia F. A1 - Cioffi, Marcelo B. T1 - Hypermethylated Chromosome Regions in Nine Fish Species with Heteromorphic Sex Chromosomes JF - Cytogenetic and Genome Research N2 - Sites and amounts of 5-methylcytosine (5-MeC)-rich chromosome regions were detected in the karyotypes of 9 Brazilian species of Characiformes fishes by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. These species, belonging to the genera Leporinus, Triportheus and Hoplias, are characterized by highly differentiated and heteromorphic ZW and XY sex chromosomes. In all species, the hypermethylated regions are confined to constitutive heterochromatin. The number and chromosome locations of hypermethylated heterochromatic regions in the karyotypes are constant and species-specific. Generally, heterochromatic regions that are darkly stained by the C-banding technique are distinctly hypermethylated, but several of the brightly fluorescing hypermethylated regions merely exhibit moderate or faint C-banding. The ZW and XY sex chromosomes of all 9 analyzed species also show species-specific heterochromatin hypermethylation patterns. The analysis of 5-MeC-rich chromosome regions contributes valuable data for comparative cytogenetics of closely related species and highlights the dynamic process of differentiation operating in the repetitive DNA fraction of sex chromosomes. KW - heterochromatin KW - heteromorphic sex chromosomes KW - hypermethylation KW - immunofluorescence KW - 5-Methylcytosine KW - fish Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196710 SN - 1424-8581 SN - 1424-859X N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 147 IS - 2-3 ER - TY - JOUR A1 - Vaiopoulos, Aristeidis G. A1 - Kanakis, Meletios A. A1 - Kapsimali, Violetta A1 - Vaiopoulos, Georgios A1 - Kaklamanis, Phedon G. A1 - Zouboulis, Christos C. T1 - Juvenile Adamantiades-Behçet disease JF - Dermatology N2 - Adamantiades-Behçet disease (ABD) is a chronic, multisystemic, recurrent, inflammatory vascular disorder of unknown etiology. Patients with symptoms initially appearing at the age of 16 or less are considered as cases of juvenile-onset ABD (JABD). JABD is relatively rare compared to ABD of adults, and only case reports and case studies have been published regarding this subtype of the disease. Epidemiology, clinical features, diagnosis and treatment of JABD are discussed in this review. KW - Aphthae KW - Childhood KW - Epidemiological study KW - Genitoanal region KW - Adamantiades-Behçet disease KW - Behçet’s disease KW - Uveitis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196616 SN - 1018-8665 SN - 1421-9832 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 232 IS - 2 SP - 129 EP - 136 ER - TY - JOUR A1 - Pfeilschifter, Rene T1 - Jill Harries, Imperial Rome AD 284 to 363. The New Empire. (The Edinburgh History of Ancient Rome.) Edinburgh, Edinburgh University Press 2011 JF - Historische Zeitschrift N2 - Rezension zu Jill Harries, Imperial Rome AD 284 to 363. The New Empire. (The Edinburgh History of Ancient Rome.) Edinburgh, Edinburgh University Press 2011 KW - Imperial Rome KW - The New Empire Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195497 SN - 2196-680X SN - 0018-2613 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 303 IS - 3 ER - TY - JOUR A1 - Aurast, Anna A1 - Gradl, Tobias A1 - Pernes, Stefan A1 - Pielström, Steffen T1 - Big Data und Smart Data in den Geisteswissenschaften JF - Bibliothek Forschung und Praxis N2 - Kein Abstract verfügbar. KW - Textanalyse KW - unstrukturierte Daten KW - Natural Language Processing KW - Text analysis KW - unstructured data KW - natural language processing Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195237 SN - 1865-7648 SN - 0341-4183 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 40 IS - 2 ER - TY - JOUR A1 - Laubenthal, Klaus T1 - Strafvollzug JF - Zeitschrift für die gesamte Strafrechtswissenschaft N2 - Kein Abstract verfügbar. KW - Strafvollzug Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195349 SN - 1612-703X SN - 0084-5310 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 127 IS - 4 ER - TY - JOUR A1 - Schmidt, Rainer F. T1 - „Revanche pour Sedan“ – Frankreich und der Schlieffenplan. Militärische und bündnispolitische Vorbereitung des Ersten Weltkriegs JF - Historische Zeitschrift N2 - In der mehr als einhundertjährigen Debatte über die Gründe und die Verantwortung für den Ausbruch des Ersten Weltkrieges blieb ein wesentlicher Faktor bislang unberücksichtigt: die französische Detailkenntnis des Schlieffenplans. Der Beitrag entwickelt die These, dass dieses Wissen um das seit 1913 alternativlose militärische Vorgehen des Deutschen Reiches sowie die sich hieraus ergebenden Handlungszwänge für Berlin zum Kompassbuch der Außen- und Militärpolitik Frankreichs vor dem Kriegsbeginn wurde. Als Ministerpräsident und als Staatspräsident verfolgte Poincaré eine Kriegsvorbereitungs- und Erpressungspolitik gegenüber Berlin. Sie sollte nicht nur die Sicherheit Frankreichs vor Deutschland verbürgen. Ihr Ziel und ihre Perspektive waren vielmehr die einer Revanche für 1870/71, um, analog zu Bismarcks Vorgehen in der „Hohenzollernkrise“, die Berliner Reichsleitung in eine Situation zu manövrieren, in der sich diese zur Flucht nach vorne in die Kriegsauslösung entschloss. Deshalb wurde die Entente Cordiale mit England zu einem de facto-Militärbündnis ausgebaut; deshalb agierte Poincaré als Geburtshelfer der Unterhandlungen für eine Marinekonvention zwischen London und Petersburg; und deshalb gab er der Pariser Balkanpolitik eine neue Ausrichtung, indem er die seit 1893/94 bestehende Beistandsautomatik gegenüber Rußland grundlegend modifizierte. Jetzt wurden die russischen Expansionsziele auf dem Balkan als handlungsleitendes Motiv der Pariser Politik adoptiert; jetzt wurde Petersburg angespornt, gegen Wien offensiv aufzutreten; jetzt bekamen die russischen Entscheidungsträger, anders als noch in der „bosnischen Annexionskrise“, die Versicherung uneingeschränkten französischen Beistands auf dem Balkan; und jetzt wurde mit Petersburg ein mit Anleihen unterfüttertes Kompensationsgeschäft abgeschlossen, das sich sowohl diplomatisch wie vor allem militärisch gegen Deutschland richtete und die Prämissen des Schlieffenplans zunehmend aushebelte. All diese Vorkehrungen dienten dazu, die Unzulänglichkeiten der eigenen militärstrategischen Aufstellung gemäß „Plan XVII“ auszubalancieren, die offene belgische Flanke abzudichten, die eminenten Bedenken der eigenen Generalität zu zerstreuen und Frankreich in einem Krieg an der Seite Russlands und Englands eine Siegchance zu verschaffen. Vor allem aber erfüllten sie den Zweck, Deutschland herauszufordern und unter enormen Handlungsdruck zu setzen. Die von Poincaré angeheizten Einkreisungsphobien in der deutschen Führungsspitze ebneten somit Berlin den Weg in die hochriskante und nicht beherrschbare Konfrontations- und Risikopolitik der „Julikrise“. Poincarés Kalkül erfüllt den Tatbestand einer indirekten Kriegsentfesselung. KW - Connectivity KW - World War I KW - Kriegspolitik KW - Kriegsvorbereitung KW - Entente Cordiale Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195379 SN - 2196-680X SN - 0018-2613 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 303 IS - 2 ER - TY - JOUR A1 - Essler, Holger T1 - Phylenzahl und Phylenzyklus in Hermupolis und Oxyrhynchos JF - Archiv für Papyrusforschung und verwandte Gebiete N2 - While the tribal cycles in Oxyrhynchos are fairly well attested from AD 206 until 271, no system has been proposed for other periods or other metropoleis. On the basis of recently published texts a first attempt is made to reconstruct the tribal cycles in Oxyrhynchus and Hermopolis for the later part of the 4th century. KW - Hermopolis KW - Oxyrhynchos KW - tribes KW - liturgy KW - administration Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195465 SN - 1867-1551 SN - 0066-6459 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 62 IS - 1 ER - TY - CHAP A1 - Appel, Alexandra T1 - Multi-Channel-Einzelhandel und Embeddedness - das Beispiel Migros Sanal Market in der Türkei T2 - Online-Handel ist Wandel N2 - No abstract available. KW - Multi-Channel-Einzelhandel KW - Embeddedness KW - Migros Sanal Market KW - Türkei Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-182662 ER - TY - JOUR A1 - Verma, Pramod Kumar A1 - Steinbacher, Andreas A1 - Schmiedel, Alexander A1 - Nuernberger, Patrick A1 - Brixner, Tobias T1 - Excited-state intramolecular proton transfer of 2-acetylindan-1,3-dione studied by ultrafast absorption and fluorescence spectroscopy JF - Structural Dynamics N2 - We employ transient absorption from the deep-UV to the visible region and fluorescence upconversion to investigate the photoinduced excited-state intramolecular proton-transfer dynamics in a biologically relevant drug molecule, 2-acetylindan-1,3-dione. The molecule is a ß-diketone which in the electronic ground state exists as exocyclic enol with an intramolecular H-bond. Upon electronic excitation at 300 nm, the first excited state of the exocyclic enol is initially populated, followed by ultrafast proton transfer (≈160 fs) to form the vibrationally hot endocyclic enol. Subsequently, solvent-induced vibrational relaxation takes place (≈10 ps) followed by decay (≈390 ps) to the corresponding ground state. KW - time resolved spectroscopy KW - ground states KW - fluorescence spectra KW - absorption spectra KW - ultraviolet light KW - hydrogen bonding KW - excited states KW - reaction mechanisms KW - fluorescence KW - solvents Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181301 VL - 3 ER - TY - CHAP A1 - Ott, Christine T1 - Zur Ver- und Entschränkung von Schulbucharbeit und Schulbuchzulassung. Theoretische Grundlegung und historische Skizze. T2 - Schulbücher auf dem Prüfstand N2 - Kein Abstract verfügbar. KW - Schulbucharbeit KW - Schulbuchzulassung Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203986 UR - https://www.klinkhardt.de/verlagsprogramm/2132.html PB - Verlag Julius Klinkhardt ER - TY - JOUR A1 - Münst, Bernhard A1 - Thier, Marc Christian A1 - Winnemöller, Dirk A1 - Helfen, Martina A1 - Thummer, Rajkumar P. A1 - Edenhofer, Frank T1 - Nanog induces suppression of senescence through downregulation of p27\(^{KIP1}\) expression JF - Journal of Cell Science N2 - A comprehensive analysis of the molecular network of cellular factors establishing and maintaining pluripotency as well as self renewal of pluripotent stem cells is key for further progress in understanding basic stem cell biology. Nanog is necessary for the natural induction of pluripotency in early mammalian development but dispensable for both its maintenance and its artificial induction. To gain further insight into the molecular activity of Nanog, we analyzed the outcomes of Nanog gain-of-function in various cell models employing a recently developed biologically active recombinant cell-permeant protein, Nanog-TAT. We found that Nanog enhances the proliferation of both NIH 3T3 and primary fibroblast cells. Nanog transduction into primary fibroblasts results in suppression of senescence-associated beta-galactosidase activity. Investigation of cell cycle factors revealed that transient activation of Nanog correlates with consistent downregulation of the cell cycle inhibitor p27\(^{KIP1}\) (also known as CDKN1B). By performing chromatin immunoprecipitation analysis, we confirmed bona fide Nanog-binding sites upstream of the p27\(^{KIP1}\) gene, establishing a direct link between physical occupancy and functional regulation. Our data demonstrates that Nanog enhances proliferation of fibroblasts through transcriptional regulation of cell cycle inhibitor p27 gene. KW - Embryonic stem cell KW - Protein transduction KW - Pluripotency KW - Senescence KW - Cell reprogramming KW - p27(KIP1) Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190761 VL - 129 IS - 5 ER - TY - JOUR A1 - Ehnert, Ina A1 - Parsa, Sepideh A1 - Roper, Ian A1 - Wagner, Marcus A1 - Muller-Camen, Michael T1 - Reporting on sustainability and HRM: a comparative study of sustainability reporting practices by the world's largest companies JF - International Journal of Human Resource Management N2 - As a response to the growing public awareness on the importance of organisational contributions to sustainable development, there is an increased incentive for corporations to report on their sustainability activities. In parallel with this has been the development of Sustainable HRM' which embraces a growing body of practitioner and academic literature connecting the notions of corporate sustainability to HRM. The aim of this article is to analyse corporate sustainability reporting amongst the world's largest companies and to assess the HRM aspects of sustainability within these reports in comparison to environmental aspects of sustainable management and whether organisational attributes - principally country-of-origin - influences the reporting of such practices. A focus in this article is the extent to which the reporting of various aspects of sustainability may reflect dominant models of corporate governance in the country in which a company is headquartered. The findings suggest, first and against expectations, that the overall disclosure on HRM-related performance is not lower than that on environmental performance. Second, companies report more on their internal workforce compared to their external workforce. Finally, international differences, in particular those between companies headquartered in liberal market economies and coordinated market economies, are not as apparent as expected. KW - Human Resource Management KW - comparative HRM KW - global reporting initiative KW - sustainability reporting KW - Sustainable HRM Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191141 VL - 27 IS - 1 ER - TY - JOUR A1 - Daryaee, Fereidoon A1 - Chang, Andrew A1 - Schiebel, Johannes A1 - Lu, Yang A1 - Zhang, Zhuo A1 - Kapilashrami, Kanishk A1 - Walker, Stephen G. A1 - Kisker, Caroline A1 - Sotriffer, Christoph A. A1 - Fisher, Stewart L. A1 - Tonge, Peter J. T1 - Correlating drug-target kinetics and in vivo pharmacodynamics: long residence time inhibitors of the FabI enoyl-ACP reductase JF - Chemical Science N2 - Drug-target kinetics enable time-dependent changes in target engagement to be quantified as a function of drug concentration. When coupled to drug pharmacokinetics (PK), drug-target kinetics can thus be used to predict in vivo pharmacodynamics (PD). Previously we described a mechanistic PK/PD model that successfully predicted the antibacterial activity of an LpxC inhibitor in a model of Pseudomonas aeruginosa infection. In the present work we demonstrate that the same approach can be used to predict the in vivo activity of an enoyl-ACP reductase (FabI) inhibitor in a model of methicillin-resistant Staphylococcus aureus (MRSA) infection. This is significant because the LpxC inhibitors are cidal, whereas the FabI inhibitors are static. In addition P. aeruginosa is a Gram-negative organism whereas MRSA is Gram-positive. Thus this study supports the general applicability of our modeling approach across antibacterial space. KW - Staphylococcus aureus KW - antibacterial activity KW - LpxC inhibitors KW - enoyl-ACP reductase inhibitors Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191218 VL - 7 IS - 9 ER - TY - JOUR A1 - El Hajj, Nady A1 - Dittrich, Marcus A1 - Böck, Julia A1 - Kraus, Theo F. J. A1 - Nanda, Indrajit A1 - Müller, Tobias A1 - Seidmann, Larissa A1 - Tralau, Tim A1 - Galetzka, Danuta A1 - Schneider, Eberhard A1 - Haaf, Thomas T1 - Epigenetic dysregulation in the developing Down syndrome cortex JF - Epigenetics N2 - Using Illumina 450K arrays, 1.85% of all analyzed CpG sites were significantly hypermethylated and 0.31% hypomethylated in fetal Down syndrome (DS) cortex throughout the genome. The methylation changes on chromosome 21 appeared to be balanced between hypo- and hyper-methylation, whereas, consistent with prior reports, all other chromosomes showed 3-11times more hyper- than hypo-methylated sites. Reduced NRSF/REST expression due to upregulation of DYRK1A (on chromosome 21q22.13) and methylation of REST binding sites during early developmental stages may contribute to this genome-wide excess of hypermethylated sites. Upregulation of DNMT3L (on chromosome 21q22.4) could lead to de novo methylation in neuroprogenitors, which then persists in the fetal DS brain where DNMT3A and DNMT3B become downregulated. The vast majority of differentially methylated promoters and genes was hypermethylated in DS and located outside chromosome 21, including the protocadherin gamma (PCDHG) cluster on chromosome 5q31, which is crucial for neural circuit formation in the developing brain. Bisulfite pyrosequencing and targeted RNA sequencing showed that several genes of PCDHG subfamilies A and B are hypermethylated and transcriptionally downregulated in fetal DS cortex. Decreased PCDHG expression is expected to reduce dendrite arborization and growth in cortical neurons. Since constitutive hypermethylation of PCDHG and other genes affects multiple tissues, including blood, it may provide useful biomarkers for DS brain development and pharmacologic targets for therapeutic interventions. KW - trisomy 21 KW - DNA methylation KW - Down syndrome KW - fetal brain development KW - frontal cortex KW - protocadherin gamma cluster Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191239 VL - 11 IS - 8 ER - TY - JOUR A1 - Bratengeier, Klaus A1 - Holubyev, Kostyantyn T1 - Anisotropy of dose contributions-an instrument to upgrade real time IMRT and VMAT adaptation? JF - Medical Physics N2 - Purpose: To suggest a definition of dose deposition anisotropy for the purpose of ad hoc adaptation of intensity modulated arc therapy (IMRT) and volumetric arc therapy (VMAT), particularly in the vicinity of important organs at risk (OAR), also for large deformations. Methods: Beam's-eye-view (BEV) based fluence warping is a standard adaptation method with disadvantages for strongly varying OAR shapes. 2-Step-adaptation overcomes these difficulties by a deeper analysis of the 3D properties of adaptation processes, but requires separate arcs for every OAR to spare, which makes it impractical for cases with multiple OARs. The authors aim to extend the 2-Step method to arbitrary intensity modulated plan by analyzing the anisotropy of dose contributions. Anisotropy was defined as a second term of Fourier transformation of gantry angle dependent dose contributions. For a cylindrical planning target volume (PTV) surrounding an OAR of varying diameter, the anisotropy and the dose-normalized anisotropy were analyzed for several scenarios of optimized fluence distributions. 2-Step adaptation to decreasing and increasing OAR diameter was performed, and compared to a usual fluence based adaptation method. For two clinical cases, prostate and neck, the VMAT was generated and the behavior of anisotropy was qualitatively explored for deformed organs at risk. # Results: Dose contribution anisotropy in the PTV peaks around nearby OARs. The thickness of the "anisotropy wall" around OAR increases for increasing OAR radius, as also does the width of 2-Step dose saturating fluence peak adjacent to the OAR K. Bratengeier et al., "A comparison between 2-Step IMRT and conventional IMRT planning," Radiother. Oncol. 84, 298-306 (2007)]. Different optimized beam fluence profiles resulted in comparable radial dependence of normalized anisotropy. As predicted, even for patient cases, anisotropy was inflated even more than increasing diameters of OAR. Conclusions: For cylindrically symmetric cases, the dose distribution anisotropy defined in the present work implicitly contains adaptation-relevant information about 3D relationships between PTV and OAR and degree of OAR sparing. For more complex realistic cases, it shows the predicted behavior qualitatively. The authors claim to have found a first component for advancing a 2-Step adaptation to a universal adaptation algorithm based on the BEV projection of the dose anisotropy. Further planning studies to explore the potential of anisotropy for adaptation algorithms using phantoms and clinical cases of differing complexity will follow. KW - modulated arc therapy KW - 2-step IMRT KW - radiation-therapy KW - online adaption KW - prostate-cancer KW - plans KW - IMAT KW - tracking KW - radiotherapy KW - adaption KW - IMRT KW - VMAT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186833 VL - 43 IS - 11 ER - TY - JOUR A1 - Dotterweich, Julia A1 - Schlegelmilch, Katrin A1 - Keller, Alexander A1 - Geyer, Beate A1 - Schneider, Doris A1 - Zeck, Sabine A1 - Tower, Robert J. J. A1 - Ebert, Regina A1 - Jakob, Franz A1 - Schütze, Norbert T1 - Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells-implications for myeloma bone disease JF - Bone N2 - Physical interaction of skeletal precursors with multiple myeloma cells has been shown to suppress their osteogenic potential while favoring their tumor-promoting features. Although several transcriptome analyses of myeloma patient-derived mesenchymal stem cells have displayed differences compared to their healthy counterparts, these analyses insufficiently reflect the signatures mediated by tumor cell contact, vary due to different methodologies, and lack results in lineage-committed precursors. To determine tumor cell contact-mediated changes on skeletal precursors, we performed transcriptome analyses of mesenchymal stem cells and osteogenic precursor cells cultured in contact with the myeloma cell line INA-6. Comparative analyses confirmed dysregulation of genes which code for known disease-relevant factors and additionally revealed upregulation of genes that are associated with plasma cell homing, adhesion, osteoclastogenesis, and angiogenesis. Osteoclast-derived coupling factors, a dysregulated adipogenic potential, and an imbalance in favor of anti-anabolic factors may play a role in the hampered osteoblast differentiation potential of mesenchymal stem cells. Angiopoietin-Like 4 (ANGPTL4) was selected from a list of differentially expressed genes as a myeloma cell contact-dependent target in skeletal precursor cells which warranted further functional analyses. Adhesion assays with full-length ANGPTL4-coated plates revealed a potential role of this protein in INA6 cell attachment. This study expands knowledge of the myeloma cell contact-induced signature in the stromal compartment of myelomatous bones and thus offers potential targets that may allow detection and treatment of myeloma bone disease at an early stage. KW - marrow stromal cells KW - Endothelial growth-factor KW - precedes multiple-myeloma KW - monoclonial gammopathy KW - in-vitro KW - mesenchymal stem-cells KW - undetermined significance KW - angiogenic cytokines KW - peripheral-blood KW - gene-expression KW - Multiple myeloma KW - Bone disease KW - Angiopoietin-like 4 KW - Gene expression profiling KW - Mesenchymal stem cells KW - Osteogenic precursor cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186688 VL - 93 ER - TY - JOUR A1 - Scharaw, Sandra A1 - Iskar, Murat A1 - Ori, Alessandro A1 - Boncompain, Gaelle A1 - Laketa, Vibor A1 - Poser, Ina A1 - Lundberg, Emma A1 - Perez, Franck A1 - Beck, Martin A1 - Bork, Peer A1 - Pepperkok, Rainer T1 - The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR JF - Journal of Cell Biology N2 - Stimulation of cells with epidermal growth factor (EGF) induces internalization and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway. For continuous cell functioning, EGFR plasma membrane levels are maintained by transporting newly synthesized EGFRs to the cell surface. The regulation of this process is largely unknown. In this study, we find that EGF stimulation specifically increases the transport efficiency of newly synthesized EGFRs from the endoplasmic reticulum to the plasma membrane. This coincides with an up-regulation of the inner coat protein complex II (COP II) components SEC23B, SEC24B, and SEC24D, which we show to be specifically required for EGFR transport. Up-regulation of these COP II components requires the transcriptional regulator RNF11, which localizes to early endosomes and appears additionally in the cell nucleus upon continuous EGF stimulation. Collectively, our work identifies a new regulatory mechanism that integrates the degradation and transport of EGFR in order to maintain its physiological levels at the plasma membrane. KW - Epidermal growth-factor KW - finger protein 11 KW - receptor tyrosine kinases KW - early secretory pathway KW - breast-cancer KW - brefeldin-a KW - E3 ligase KW - trafficking KW - export KW - endoplasmic-reticulum Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186731 VL - 215 IS - 4 ER - TY - JOUR A1 - Dekant, Wolfgang A1 - Bridges, James T1 - Assessment of reproductive and developmental effects of DINP, DnHP and DCHP using quantitative weight of evidence JF - Regulatory Toxicology and Pharmacology N2 - Quantitative weight of evidence (QWoE) methodology utilizes detailed scoring sheets to assess the quality/reliability of each publication on toxicity of a chemical and gives numerical scores for quality and observed toxicity. This QWoE-methodology was applied to the reproductive toxicity data on diisononylphthalate (DINP), di-n-hexylphthalate (DnHP), and dicyclohexylphthalate (DCHP) to determine if the scientific evidence for adverse effects meets the requirements for classification as reproductive toxicants. The scores for DINP were compared to those when applying the methodology DCHP and DnHP that have harmonized classifications. Based on the quality/reliability scores, application of the QWoE shows that the three databases are of similar quality; but effect scores differ widely. Application of QWoE to DINP studies resulted in an overall score well below the benchmark required to trigger classification. For DCHP, the QWoE also results in low scores. The high scores from the application of the QWoE methodology to the toxicological data for DnHP represent clear evidence for adverse effects and justify a classification of DnHP as category 1B for both development and fertility. The conclusions on classification based on the QWoE are well supported using a narrative assessment of consistency and biological plausibility. KW - n-hexyl phthalate KW - male rats KW - dicyclohexyl phthalate KW - Diisononyl phthalate KW - in-vivo KW - 2-Generation reproduction KW - testosterone production KW - sexual development KW - risk-assesment KW - fetal testis KW - weight of evidence KW - classification and labeling KW - reproductive and developmental toxicity KW - quantitative assessments Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186750 VL - 81 ER - TY - JOUR A1 - Münch, Miriam A1 - Hsin, Chih-Hsuan A1 - Ferber, Elena A1 - Berger, Susanne A1 - Müller, Martin J. T1 - Reactive electrophilic oxylipins trigger a heat stress-like response through HSFA1 transcription factors JF - Journal of Experimental Botany N2 - Electrophilic oxylipins trigger a heat-shock-like response in the absence of heat through the canonical heat-shock transcription factor A1, thereby helping to cope with stresses associated with protein damage.Abiotic and biotic stresses are often characterized by an induction of reactive electrophile species (RES) such as the jasmonate 12-oxo-phytodienoic acid (OPDA) or the structurally related phytoprostanes. Previously, RES oxylipins have been shown massively to induce heat-shock-response (HSR) genes including HSP101 chaperones. Moreover, jasmonates have been reported to play a role in basal thermotolerance. We show that representative HSR marker genes are strongly induced by RES oxylipins through the four master regulator transcription factors HSFA1a, b, d, and e essential for short-term adaptation to heat stress in Arabidopsis. When compared with Arabidopsis seedlings treated at the optimal acclimation temperature of 37 A degrees C, the exogenous application of RES oxylipins at 20 A degrees C induced a much weaker induction of HSP101 at both the gene and protein expression levels which, however, was not sufficient to confer short-term acquired thermotolerance. Moreover, jasmonate-deficient mutant lines displayed a wild-type-like HSR and were not compromised in acquiring thermotolerance. Hence, the OPDA- and RES oxylipin-induced HSR is not sufficient to protect seedlings from severe heat stress but may help plants to cope better with stresses associated with protein unfolding by inducing a battery of chaperones in the absence of heat. KW - arabidopsis-thaliana KW - shock response KW - gene-expression KW - model KW - acquired thermotolerance KW - 12-oxo-phytodienoic acid KW - thermotolerance KW - plants KW - detoxification KW - acquisition KW - activation KW - heat stress KW - jasmonates KW - phytoprostanes KW - reactive electrophilic species KW - unfolded protein response Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186766 VL - 67 IS - 21 ER - TY - JOUR A1 - Joensuu, Johanna A1 - Altimir, Nuria A1 - Hakola, Hannele A1 - Rostás, Michael A1 - Raivonen, Maarit A1 - Vestenius, Mika A1 - Aaltonen, Hermanni A1 - Riederer, Markus A1 - Bäck, Jaana T1 - Role of needle surface waxes in dynamic exchange of mono- and sesquiterpenes JF - Atmospheric Chemistry and Physics N2 - Biogenic volatile organic compounds (BVOCs) produced by plants have a major role in atmospheric chemistry. The different physicochemical properties of BVOCs affect their transport within and out of the plant as well as their reactions along the way. Some of these compounds may accumulate in or on the waxy surface layer of conifer needles and participate in chemical reactions on or near the foliage surface. The aim of this work was to determine whether terpenes, a key category of BVOCs produced by trees, can be found on the epicuticles of Scots pine (Pinus sylvestris L.) and, if so, how they compare with the terpenes found in shoot emissions of the same tree. We measured shoot-level emissions of pine seedlings at a remote outdoor location in central Finland and subsequently analysed the needle surface waxes for the same compounds. Both emissions and wax extracts were clearly dominated by monoterpenes, but the proportion of sesquiterpenes was higher in the wax extracts. There were also differences in the terpene spectra of the emissions and the wax extracts. The results, therefore, support the existence of BVOC associated to the epicuticular waxes. We briefly discuss the different pathways for terpenes to reach the needle surfaces and the implications for air chemistry. KW - needle surface waxes KW - biogenic volatile organic compounds KW - Pinus sylvestris L. KW - atmospheric chemistry Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171324 VL - 16 IS - 12 ER - TY - JOUR A1 - Lorenz, Sonja A1 - Bhattacharyya, Moitrayee A1 - Feiler, Christian A1 - Rape, Michael A1 - Kuriyan, John T1 - Crystal Structure of a Ube2S-Ubiquitin Conjugate JF - PLoS ONE N2 - Protein ubiquitination occurs through the sequential formation and reorganization of specific protein-protein interfaces. Ubiquitin-conjugating (E2) enzymes, such as Ube2S, catalyze the formation of an isopeptide linkage between the C-terminus of a “donor” ubiquitin and a primary amino group of an “acceptor” ubiquitin molecule. This reaction involves an intermediate, in which the C-terminus of the donor ubiquitin is thioester-bound to the active site cysteine of the E2 and a functionally important interface is formed between the two proteins. A docked model of a Ube2S-donor ubiquitin complex was generated previously, based on chemical shift mapping by NMR, and predicted contacts were validated in functional studies. We now present the crystal structure of a covalent Ube2S-ubiquitin complex. The structure contains an interface between Ube2S and ubiquitin in trans that resembles the earlier model in general terms, but differs in detail. The crystallographic interface is more hydrophobic than the earlier model and is stable in molecular dynamics (MD) simulations. Remarkably, the docked Ube2S-donor complex converges readily to the configuration seen in the crystal structure in 3 out of 8 MD trajectories. Since the crystallographic interface is fully consistent with mutational effects, this indicates that the structure provides an energetically favorable representation of the functionally critical Ube2S-donor interface. KW - crystal structure KW - protein ubiquitination KW - Ubiquitin-conjugating (E2) enzymes KW - Ube2S Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167265 VL - 11 IS - 2 ER - TY - JOUR A1 - Bahník, Štěpán A1 - Strack, Fritz T1 - Overlap of accessible information undermines the anchoring effect JF - Judgment and Decision Making N2 - According to the Selective Accessibility Model of anchoring, the comparison question in the standard anchoring paradigm activates information that is congruent with an anchor. As a consequence, this information will be more likely to become the basis for the absolute judgment which will therefore be assimilated toward the anchor. However, if the activated information overlaps with information that is elicited by the absolute judgment itself, the preceding comparative judgment should not exert an incremental effect and should fail to result in an anchoring effect. The present studies find this result when the comparative judgment refers to a general category and the absolute judgment refers to a subset of the general category that was activated by the anchor value. For example, participants comparing the average annual temperature in New York City to a high 102 °F judged the average winter, but not summer temperature to be higher than participants making no comparison. On the other hand, participants comparing the annual temperature to a low –4 °F judged the average summer, but not winter temperature to be lower than control participants. This pattern of results was shown also in another content domain. It is consistent with the Selective Accessibility Model but difficult to reconcile with other main explanations of the anchoring effect. KW - anchoring KW - judgment KW - heuristics and biases KW - selective accessibility Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169287 VL - 11 IS - 1 ER - TY - JOUR A1 - Bekes, Inga A1 - Friedl, Thomas W. P. A1 - Köhler, Tanja A1 - Möbus, Volker A1 - Janni, Wolfgang A1 - Wöckel, Achim A1 - Wulff, Christine T1 - Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer? JF - Molecular Cancer N2 - Background Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types. Methods Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition. Results VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5. Conclusions Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition. KW - ovarian cancer KW - vascular permeability KW - ascites KW - VEGF KW - claudin 5 KW - VE-cadherin Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169298 VL - 15 IS - 13 ER - TY - JOUR A1 - Tomasek, Stefan A1 - Ott, Christine T1 - Nils Mohl und Hartmann von Aue. Zur intertextuellen Verweisstruktur in Stadtrandritter und ihrem didaktischen Potential für den Deutschunterricht. JF - Literatur im Unterricht – Texte der Gegenwartsliteratur für die Schule N2 - Kein Abstract verfügbar. KW - Nils Mohl KW - Hartmann von Aue KW - Stadtrandritter KW - Deutschunterricht Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-210590 UR - http://www.wvttrier.de/top/beschreibungen/ID1562.html ER - TY - CHAP A1 - Ott, Christine T1 - 40 Jahre Geschlechterforschung zu Rechen- und Mathematikbüchern. Forschungsparadigmen und Methodik im Wandel T2 - Mathematik und Gender: Frauen in der Mathematikgeschichte – Mädchen und Mathematikunterricht heute N2 - Kein Abstract verfügbar. KW - Mathematikbücher KW - Schulbuch KW - Geschlechterforschung KW - Forschungsparadigma Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-210629 UR - https://verlagfranzbecker.de/ PB - Franzbecker ER - TY - INPR A1 - Ott, Christine T1 - Geschlechterstereotypen auf der Spur. Ein Plädoyer für mehr Linguistik in der Bildungsforschung T2 - Bildung und Differenz. Historische Analysen zu einem aktuellen Problem N2 - Kein Abstract verfügbar. KW - Geschlechterforschung KW - Stereotype KW - Schulbuch Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-210503 ER - TY - JOUR A1 - Huang, Guozheng A1 - Schramm, Simon A1 - Heilmann, Jörg A1 - Biedermann, David A1 - Kren, Vladimír A1 - Decker, Michael T1 - Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins JF - Beilstein Journal of Organic Chemistry N2 - Various Mitsunobu conditions were investigated for a series of flavonolignans (silybin A, silybin B, isosilybin A, and silychristin A) to achieve either selective esterification in position C-23 or dehydration in a one-pot reaction yielding the biologically important enantiomers of hydnocarpin D, hydnocarpin and isohydnocarpin, respectively. This represents the only one-pot semi-synthetic method to access these flavonolignans in high yields. KW - Mitsunobu KW - dehydration KW - flavonoid KW - hydnocarpin KW - silybin Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160986 VL - 12 ER - TY - JOUR A1 - Zinner, C. A1 - Krueger, M. A1 - Reed, J. L. A1 - Kohl-Bareis, M. A1 - Holmberg, H. C. A1 - Sperlich, B. T1 - Exposure to a combination of heat and hyperoxia during cycling at submaximal intensity does not alter thermoregulatory responses JF - Biology of Sport N2 - In this study, we tested the hypothesis that breathing hyperoxic air (F\(_{in}\)O\(_2\) = 0.40) while exercising in a hot environment exerts negative effects on the total tissue level of haemoglobin concentration (tHb); core (T\(_{core}\)) and skin (T\(_{skin}\)) temperatures; muscle activity; heart rate; blood concentration of lactate; pH; partial pressure of oxygen (P\(_a\)O\(_2\)) and carbon dioxide; arterial oxygen saturation (S\(_a\)O\(_2\)); and perceptual responses. Ten well-trained male athletes cycled at submaximal intensity at 21°C or 33°C in randomized order: first for 20 min while breathing normal air (FinO\(_2\) = 0.21) and then 10 min with F\(_{in}\)O\(_2\) = 0.40 (HOX). At both temperatures, S\(_a\)O\(_2\) and P\(_a\)O\(_2\), but not tHb, were increased by HOX. Tskin and perception of exertion and thermal discomfort were higher at 33°C than 21°C (p < 0.01), but independent of F\(_{in}\)O\(_2\). T\(_{core}\) and muscle activity were the same under all conditions (p > 0.07). Blood lactate and heart rate were higher at 33°C than 21°C. In conclusion, during 30 min of submaximal cycling at 21°C or 33°C, T\(_{core}\), T\(_{skin}\) and T\(_{body}\), tHb, muscle activity and ratings of perceived exertion and thermal discomfort were the same under normoxic and hyperoxic conditions. Accordingly, breathing hyperoxic air (F\(_{in}\)O\(_2\) = 0.40) did not affect thermoregulation under these conditions. KW - heat stress KW - hyperthermia KW - skin blood flow KW - thermoregulation KW - vasoconstriction Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160993 VL - 33 IS - 1 ER - TY - JOUR A1 - Joukhadar, R. A1 - Wöckel, A. A1 - Herr, D. A1 - Paulus, V. A1 - Radosa, J. A1 - Hamza, A. A1 - Solomayer, E. A1 - Baum, S. T1 - Challenges of Longevity: Safety of Vaginal and Laparoscopic Urogynecological Procedures in Septuagenarians and Older Patients JF - BioMed Research International N2 - Introduction. Pelvic organ prolapse (POP) and urinary incontinence (UI) have increasing prevalence in the elderly population. The aim of this study was to compare the comorbidities of these procedures between <70 y/o and ≥70 y/o patients. Materials and Methods. In our retrospective study over a period of 2.5 years, 407 patients had received an urogynecological procedure. All patients with POP were treated by reconstructive surgery. Complications were reported using the standardized classification of Clavien-Dindo (CD). The study can be assigned to stage 2b Exploration IDEAL (Idea, Development, Exploration, Assessment, Long-term study)-system of surgical innovation. Results. Operation time, blood loss, and intraoperative complications have not been more frequent in the elderly, whereas hospital stay was significantly longer in ≥70 y/o patients. Regarding postoperative complications, we noticed that ≥70 y/o patients had an almost threefold risk to develop mild early postoperative complications compared to younger patients (OR: 2.86; 95% CI: 1.76–4.66). On the contrary, major complications were not more frequent. No case of life-threatening complication or the need for blood transfusion was reported. Conclusion. After urogynecological procedures, septuagenarians and older patients are more likely to develop mild postoperative complications but not more intraoperative or severe postoperative complications compared to younger patients. KW - gynecologic surgical procedures/methods KW - postoperative complications/epidemiology KW - vagina/surgery KW - pelvic organ prolapse/surgery KW - middle Aged KW - laparoscopy/methods KW - uterine prolapse/surgery KW - urinary incontinence/surgery KW - surgical Mesh KW - retrospective Studies KW - age factors KW - aged KW - aged 80 and over KW - female KW - reconstructive surgical procedures/methods Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161005 VL - 2016 IS - Article ID 5184595 ER - TY - JOUR A1 - Isaias, Ioannis U. A1 - Trujillo, Paula A1 - Summers, Paul A1 - Marotta, Giorgio A1 - Mainardi, Luca A1 - Pezzoli, Gianni A1 - Zecca, Luigi A1 - Costa, Antonella T1 - Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease JF - Frontiers in Aging Neuroscience N2 - Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the substantia nigra. Our main objective was to determine the correspondence between changes in the substantia nigra, evident in neuromelanin and iron sensitive magnetic resonance imaging (MRI), and dopaminergic striatal innervation loss in patients with PD. Eighteen patients and 18 healthy control subjects were included in the study. Using neuromelanin-MRI, we measured the volume of the substantia nigra and the contrast-to-noise-ratio between substantia nigra and a background region. The apparent transverse relaxation rate and magnetic susceptibility of the substantia nigra were calculated from dual-echo MRI. Striatal dopaminergic innervation was measured as density of dopamine transporter (DAT) by means of single-photon emission computed tomography and [123I] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane. Patients showed a reduced volume of the substantia nigra and contrast-to-noise-ratio and both positively correlated with the corresponding striatal DAT density. The apparent transverse relaxation rate and magnetic susceptibility values of the substantia nigra did not differ between patients and healthy controls. The best predictor of DAT reduction was the volume of the substantia nigra. Clinical and imaging correlations were also investigated for the locus coeruleus. Our results suggest that neuromelanin-MRI can be used for quantifying substantia nigra pathology in PD where it closely correlates with dopaminergic striatal innervation loss. Longitudinal studies should further explore the role of Neuromelanin-MRI as an imaging biomarker of PD, especially for subjects at risk of developing the disease. KW - MRI KW - neuromelanin KW - dopamine KW - Parkinson's disease KW - FP-CIT SPECT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164046 VL - 8 IS - 196 ER - TY - THES A1 - Lorenzin, Francesca T1 - Regulation of transcription by MYC - DNA binding and target genes T1 - Transkriptionelle Regulation durch MYC - DNA-Bindung und Zielgene N2 - MYC is a transcription factor, whose expression is elevated or deregulated in many human cancers (up to 70%) and is often associated with aggressive and poorly differentiated tumors. Although MYC is extensively studied, discrepancies have emerged about how this transcription factor works. In primary lymphocytes, MYC promotes transcriptional amplification of virtually all genes with an open promoter, whereas in tumor cells MYC regulates specific sets of genes that have significant prognostic value. Furthermore, the set of target genes that distinguish MYC’s physiological function from the pathological/oncogenic one, whether it exists or not, has not been fully understood yet. In this study, it could be shown that MYC protein levels within a cell and promoter affinity (determined by E-box presence or interaction with other proteins) of target genes toward MYC are important factors that influence MYC activity. At low levels, MYC can amplify a certain transcriptional program, which includes high affinity binding sites, whereas at high levels MYC leads to the specific up- and down regulation of genes with low affinity. Moreover, the promoter affinity characterizes different sets of target genes which can be distinguished in the physiological or oncogenic MYC signatures. MYC-mediated repression requires higher MYC levels than activation and formation of a complex with MIZ1 is necessary for inhibiting expression of a subset of MYC target genes. N2 - MYC ist ein Transkriptionsfaktor, dessen Expression in vielen humanen Tumoren (bis zu 70 %) erhöht oder dereguliert ist. Die Tumore, in denen viel MYC hergestellt wird, zeichnen sich durch einen geringen Differenzierungsgrad aus und verhalten sich sehr aggressiv. Obwohl das biologische Verhalten des MYC Proteins intensiv untersucht wurde, sind unterschiedliche Modelle, wie dieser Transkriptionsfaktor funktioniert, entwickelt worden. In primären Lymphozyten verstärkt MYC die Expression fast aller Gene mit offener Chromatinstruktur, während MYC in Tumorzellen spezifische Gengruppten reguliert, deren Expression mit der Prognose von Patienten korreliert. Es ist also unklar, ob sich die Zielgene der physiologischen Funktion von Myc von den oncogenen/pathophysiologischen Zielgenen unterscheidet und um welche Gene es sich bei letzteren handelt. In dieser Arbeit konnte gezeigt werden, dass Expressionsniveau von MYC und unterschiedliche Promotoraffinitäten zu MYC (charakterisiert durch den Ebox-Gehalt und Interaktionen zu anderen Proteinen) wichtig für die Aktivität des MYC Proteins sind. So kann Myc bei niedrigen Konzentrationen ein bestimmtes transkriptionelles Programm amplifizieren, das sich aus hochaffinen Promotoren zusammensetzt. Bei hohen Konzentrationen hingegen führt MYC zur transkriptionellen Aktivierung und Repression bestimmter Zielgengruppen, die sich durch niedrige Affinität zu MYC auszeichnen. Somit ist die Promotoraffinität ein Parameter, der physiologische von oncogenen MYC Signaturen trennen kann. Darüberhinaus konnte gezeigt werden, dass MYC-vermittelte Repression höhere MYC Mengen benötigt, als MYC-vermittelte Transaktivierung und die Komplexbildung mit MIZ1 für die Repression einer Gruppe an MYC Zielgenen nötig ist. KW - MYC KW - Transcription Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150766 ER - TY - THES A1 - Brockmann, Nicolas T1 - Kompositschichten aus dealuminiertem Zeolith Y und Hybridpolymeren auf Basis von Bis(triethoxysilyl)ethan T1 - Composite coatings made from zeolite Y and hybrid polymers based on bis(triethoxysilyl)ethane N2 - Die vorliegende Arbeit beschäftigt sich mit Kompositschichten aus Zeolithen und Hybridpolymeren, die mittels des Sol-Gel-Prozesses aus Alkyltrialkoxysilanen hergestellt werden. Am Beispiel von dealuminiertem Zeolith Y und Solen aus Bis(triethoxysilyl)ethan wurde untersucht, wie sich die Zugänglichkeit der Zeolithporen in Kompositschichten erhalten lässt. Zur Analyse der Porenzugänglichkeit kamen Gasadsorptionsmessungen zum Einsatz. Zur weiteren Charakterisierung wurden elektronenmikroskopische Aufnahmen und ausführliche spektroskopische Untersuchungen der erhaltenen Hybridpolymer-Sole durchgeführt. Die Ermittlung der mechanischen Eigenschaften erfolgte über die Messung der Wischfestigkeit. Die im Rahmen diverser Experimente erhaltenen Kompositschichten wiesen eine hohe Zeolithporenerreichbarkeit auf, sofern der Zeolithanteil mindestens 70 Volumenprozent betrug, und das jeweilige Sol einen hohen Hydrolyse- und Kondensationsgrad aufwies. Im Zusammenhang mit den genannten Studien wurden Hybridpolymere verglichen, die bei unterschiedlichen pH-Bedingungen mit verschiedenen Mengen an Wasser zur Hydrolysereaktion hergestellt wurden, oder bei denen neben Bis(triethoxysilyl)ethan Methacryloxypropyltrimethoxysilan als zweites Monomer eingesetzt wurde. Letztendlich konnten mit einfachen Mitteln Kompositschichten hergestellt werden, die auf flexible Oberflächen aufgebracht werden konnten und beim Biegen nicht vom Substrat abplatzten. Ferner waren sie wischfest und zeigten bei passender Zusammensetzung eine nahezu vollständige Zeolithporenerreichbarkeit (Zeolithanteil: ≥ 70 Vol.-%; Monomer: Bis(triethoxysilyl)ethan; Hydrolyse- und Polykondensationsreaktion: pH-Wert ≤ 2, Überschuss an Wasser). Ihr Anwendungspotential als Adsorbensschicht für die Aufnahme organischer Schadstoffe wurde beispielhaft anhand der reversiblen Adsorption von Formaldehyd demonstriert. N2 - The presented study describes composite coatings containing zeolites and hybrid polymers synthesized from alkyltrialkoxysilanes. Dealuminated zeolite Y and sols of bis(triethoxysilyl)ethane have been chosen as representatives to study which parameters affect the zeolite pore accessibility. To determine the amount of open pores, we conducted gas sorption experiments. Additionally, electron microscopy and intensive spectroscopic studies were used for further characterization. Wipe resistance has been measured to determine the mechanical properties. We studied hybrid polymers which were synthesized via sol-gel routes at different pH values, under addition of various amounts of water for the hydrolysis reaction or in the presence of methacryloxypropyltrimethoxysilane as a second monomer, besides bis(triethoxysilyl)ethane as main monomer component. Finally, the composite coatings offered high zeolite pore accessibility if the zeolite content was at least 70 vol.% and if the particular hybrid sol offered a high degree of hydrolysis and polycondensation as well as a low content of organic components. Composite coatings have been prepared by a simple manufacturing process and could be applied on flexible polymer films without cracking if the substrate was bent. In addition, the coatings were smudge-proof and offered nearly complete zeolite pore accessibility based on proper selection of the composition (zeolite content: ≥ 70 vol.%; monomer: bis(triethoxysilyl)ethane; hydrolysis and polycondensation reaction: pH value ≤ 2, excess amount of water). By observation of reversible formaldehyde adsorption, composite coatings' potential use as adsorptive agent for volatile organic compounds was successfully demonstrated. KW - Zeolith KW - Adsorptionsisotherme KW - Sol-Gel-Verfahren KW - Beschichtung KW - Ormocer KW - Kompositschicht KW - Hybridpolymer KW - Bis(triethoxysilyl)ethan KW - Alkyltrialkoxysilan Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150817 ER - TY - THES A1 - Wolfsteiner, Ulrike T1 - Kombination von arteriovenöser extrakorporaler Lungenassistenz und Hochfrequenzoszillation im Großtier-ARDS-Modell: Einfluss auf den Gasaustausch T1 - Combination of arteriovenous extracorporeal lung assist and high-frequency oscillatory ventilation in an animal-model of ARDS: influence on gas exchange N2 - Hintergrund: Durch den Einsatz der Hochfrequenzoszillationsbeatmung (HFOV) kann das applizierte Tidalvolumen minimiert und dadurch das Risiko für alveolären Scherstress reduziert werden, allerdings resultieren höhere Oszillationsfrequenzen in einer insuffizienten CO2-Elimination mit Entstehung einer Hyperkapnie und respiratorischen Azidose. In dieser experimentellen Studie wurde die Auswirkung verschiedener Oszillationsfrequenzen bei der HFOV auf die CO2-Elimination mit und ohne die Hinzunahme einer arteriovenösen extrakorporalen Lungenassistenz (avECLA) im Großtier-ARDS-Modell untersucht. Unsere Hypothese: die Verwendung hoher Oszillationsfrequenzen und damit die Minimierung des Tidalvolumens erfordert die Kombination einer HFOV mit einer avECLA, um Normokapnie zu erhalten oder wiederherzustellen. Methodik: Hierzu wurden acht gesunde Pietrain-Schweine (56,5 ± 4,4 kg) narkotisiert und intubiert und anschließend mittels pulmonaler Lavage ein schweres iatrogenes ARDS herbeigeführt. Nach einstündiger Stabilisierungsphase (PaO2 durchgehend < 80 mmHg) erfolgte ein Recruitment-Manöver und die Einstellung des mittleren Atemwegsdrucks auf 3 cmH2O über dem zuvor bestimmten unteren Inflektionspunkt. Anschließend wurden die Tiere der HFOV zugeführt, randomisiert und mit entweder auf- oder absteigenden Oszillationsfrequenzen jeweils 30 Minuten mit und ohne Hinzunahme der avECLA beatmet. Ergebnisse: Ab Oszillationsfrequenzen von 9 Hz entwickelten die Versuchstiere ohne die Hinzunahme einer avECLA zügig eine Hyperkapnie, welcher nur durch die Hinzunahme der avECLA entgegengewirkt werden konnte. Durch das Recruitment-Manöver und die Einstellung des mittleren Atemwegsdrucks auf 3 cmH2O über dem unteren Inflektionspunkt konnte die Oxygenierung dauerhaft signifikant verbessert werden (p<0.05). Die Ergebnisse der beiden Gruppen (auf- vs. absteigende Oszillationsfrequenzen) unterschieden sich dabei nicht voneinander. Zusammenfassung: Bei der Hochfrequenzoszillationsbeatmung (HFOV) konnte Normokapnie bei Oszillationsfrequenzen von 9 – 15 Hz nur durch die Kombination mit einer arteriovenösen extrakorporalen Lungenassistenz (avECLA) aufrecht erhalten werden. Zusätzlich konnte nach dem Recruitment-Manöver und der Einstellung des mittleren Atemwegsdrucks auf 3 cmH2O über dem unteren Inflektionspunkt auch noch bei sehr hohen Oszillationsfrequenzen eine dauerhafte, signifikante Verbesserung der Oxygenierung verzeichnet werden. Somit demaskiert die avECLA das lungenprotektive Potential der HFOV: die Minimierung der applizierten Tidalvolumina begrenzt nicht nur eine alveoläre Überblähung und damit Volutraumata, die Applikation höherer mittlerer Atemwegsdrücke ermöglicht darüber hinaus ein pulmonales Recruitment und schützt die Lunge damit vor Atelekttraumata. N2 - Background: During high-frequency oscillatory ventilation (HFOV) the applied tidal volume can be minimized and thereby reduce the risk of alveolar shear stress, however, higher oscillatory frequencies result in insufficient CO2-elimination with development of hypercapnia and respiratory acidosis. In this experimental study, the effect of different oscillatory frequencies in HFOV in regards to CO2-elimination with or without the combination with an arteriovenous extracorporeal lung assist (av-ECLA) was investigated in an animal-model of ARDS. Our hypothesis: the use of high oscillation frequencies and therefore the minimization of tidal volume requires the combination of HFOV with av-ECLA to maintain or reestablish normocapnia. Methods: Therefore eight healthy pigs (56.5 ± 4.4 kg) were anesthetized and intubated, followed by a pulmonary lavage to induce a severe iatrogenic ARDS. After a stabilisation period of 60 minutes (PaO2 continuously < 80 mmHg) a recruitment maneuver was performed and mean airway pressure was adjusted 3 cmH2O above the previously determined lower inflection point. The animals were then transferred to HFOV, randomized and ventilated with either ascending or descending oscillatory frequencies for 30 minutes alternating with and without av-ECLA. Results: At oscillatory frequencies of 9 Hz and above without av-ECLA, the animals rapidly developed a hypercapnia, which could only be counteracted by combining HFOV with av-ECLA. Due to the recruitment maneuver and the adjustment of the mean airway pressure to 3 cmH2O above the lower inflection point, the oxygenation could be significantly improved throughout the trial (p<0.05). The results of both groups (ascending vs. descending oscillatory frequencies) did not differ from each other. Conclusion: During high-frequency oscillatory ventilation (HFOV) with oscillatory frequencies of 9 - 15 Hz, normocapnia could only be maintained by the combination with an arteriovenous extracorporeal lung assist (av-ECLA). In addition, after recruitment maneuver and the adjustment of the mean airway pressure to 3 cmH2O above the lower inflection point, a permanent and significant improvement in the oxygenation could be observed, even at very high oscillation frequencies. Therefore, the av-ECLA unmasks the lung-protective potential of HFOV: the minimization of the applied tidal volume not only limits an alveolar over-inflation and therefore volutrauma; the application of higher mean airway pressures also enables pulmonary recruitment and therefore protects the lung from atelecttrauma. KW - ARDS KW - av-ECLA KW - Hochfrequenz-Oszillations-Ventilation KW - ARDS Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150828 ER - TY - CHAP A1 - Schmitz, Barbara T1 - Space, Borders and Boundaries in the Letter of Aristeas T2 - Borders : Terminologies, Ideologies, and Performances N2 - No abstract available. KW - Aristeas KW - Ad Philocratem KW - Aristeas-Brief KW - Letter of Aristeas KW - Aristeas, Epistolographus : Ad Philocratem Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151285 UR - https://www.mohr.de/en/book/borders-terminologies-ideologies-and-performances-9783161543760 SN - 978-3-16-154375-3 PB - Mohr Siebeck CY - Tübingen ER - TY - JOUR A1 - Schmitz, Barbara T1 - Tradition und (Er)Neuerung. Die Rede von Gott in jüdisch-hellenistischer Literatur JF - Theologische Literaturzeitung N2 - God as King is one of the metaphors that have been handed down in the biblical literature for centuries. In the Hellen­istic period talk about God as king again undergoes a change that is the conse-quence of the Hellenistic kingdom as it evolved in its specific form after the death of Alexander. The conceptual implications of the Hellenistic kingdom for talk about God is shown by reference to the epithets: the king as ἐπιφανής (»Epiphanes«), as σωτήρ (»Savior«), as εὐεργέτης (»benefactor«) and as κτίστης (»Founder«). How those epithets have affected talk of God as king is demonstrated by reference to the original Greek writings of the LXX and connected with the question of God as παντοκράτωρ (»pantocrator«). KW - Gott KW - Hellenistisch-jüdische Literatur Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151292 UR - http://www.thlz.com/artikel/18775/ VL - 141 IS - 7/8 ER - TY - JOUR A1 - Tiede, Jennifer A1 - Grafe, Silke T1 - Media Pedagogy in German and US Teacher Education JF - Communicar N2 - Varios estudios de investigación y de práctica llegan a la conclusión de que la pedagogía de los medios debe integrarse en la formación de profesores para que estos futuros docentes puedan utilizar los medios de comunicación en sus clases con eficacia y éxito. Sin embargo, estos resultados no se reflejan en los programas universitarios vigentes, de manera que en algunas instituciones los profesores en formación pueden llegar al término de sus estudios sin haber abordado cuestiones de educación en medios. Para comprender, evaluar y más adelante mejorar la situación actual de la formación del profesorado en el ámbito de la pedagogía de los medios se necesitan extensas investigaciones. Teniendo en cuenta esta situación, el siguiente artículo presenta un resumen del «statu quo» de las competencias en pedagogía de los medios de los futuros profesores, centrándose en los ejemplos de Alemania y EEUU. Para crear una base presentamos diferentes modelos de competencias pedagógicas mediáticas de ambos países e intentaremos responder a la pregunta si estas competencias son promovidas por los programas de formación del profesorado. Después, se describirán el método y resultados seleccionados de un estudio que midió las competencias en pedagogía de los medios de estudiantes de ambos países, estudio basado en un modelo generalizador de competencias pedagógicas mediáticas que conectan la investigación alemana e internacional en este campo. La perspectiva internacional comparada ayuda a extender perspectivas y comprender diferencias y similitudes. Los datos de este estudio sirven para identificar diferentes formas de integrar la pedagogía de los medios de comunicación en la formación del profesorado. Además, se pueden sacar conclusiones sobre las consecuencias que implican estos procesos para profesores en formación y sus competencias mediáticas. N2 - Various research works and practitioners conclude that media pedagogy should be integrated in teacher education in order to enable future teachers to use media for their lessons effectively and successfully. However, this realization is not necessarily reflected in actual university curricula, as preservice teachers at some places can still finish their studies without ever dealing with media pedagogical issues. To understand, assess and eventually improve the status of media pedagogical teacher education, comprehensive research is required. Against this background, the following article seeks to present a theory-based and empirical overview of the status quo of preservice teachers’ pedagogical media competencies focusing Germany and the USA exemplarily. To form a basis, different models of pedagogical media competencies from both countries will be introduced and the extent to which these competencies have become part of teacher education programs and related studies will be summarised. Afterwards, method and selected results of a study will be described where the skills in question were measured with students from both countries, based on a comprehensive model of pedagogical media competencies that connects German and international research in this field. The international comparative perspective will help broaden the viewpoint and understand differences, but also similarities. These data serve to identify different ways of integrating media pedagogy into teacher training and draw conclusions on the consequences these processes entail for preservice teachers and their pedagogical media competencies. T2 - Pedagogía mediática en la formación de profesores de Alemania y EEUU KW - enseñanzapor por competencias KW - currículum KW - análisis transnacional KW - investigación de currículo universitario KW - currículo de la educación en medios KW - alfabetización mediática KW - educación en medios KW - pedagogía KW - formación de profesorado KW - investigación KW - media literacy KW - media education KW - pedagogy KW - preservice teacher education KW - competency based teaching KW - curricula KW - research KW - crossnational analysis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162600 VL - XXIV IS - 49 ER - TY - JOUR A1 - Kaluza, Benjamin F. A1 - Wallace, Helen A1 - Heard, Tim A. A1 - Klein, Aelxandra-Maria A1 - Leonhardt, Sara D. T1 - Urban gardens promote bee foraging over natural habitats and plantations JF - Ecology and Evolution N2 - Increasing human land use for agriculture and housing leads to the loss of natural habitat and to widespread declines in wild bees. Bee foraging dynamics and fitness depend on the availability of resources in the surrounding landscape, but how precisely landscape related resource differences affect bee foraging patterns remains unclear. To investigate how landscape and its interaction with season and weather drive foraging and resource intake in social bees, we experimentally compared foraging activity, the allocation of foragers to different resources (pollen, nectar, and resin) and overall resource intake in the Australian stingless bee Tetragonula carbonaria (Apidae, Meliponini). Bee colonies were monitored in different seasons over two years. We compared foraging patterns and resource intake between the bees' natural habitat (forests) and two landscapes differently altered by humans (suburban gardens and agricultural macadamia plantations). We found foraging activity as well as pollen and nectar forager numbers to be highest in suburban gardens, intermediate in forests and low in plantations. Foraging patterns further differed between seasons, but seasonal variations strongly differed between landscapes. Sugar and pollen intake was low in plantations, but contrary with our predictions, it was even higher in gardens than in forests. In contrast, resin intake was similar across landscapes. Consequently, differences in resource availability between natural and altered landscapes strongly affect foraging patterns and thus resource intake in social bees. While agricultural monocultures largely reduce foraging success, suburban gardens can increase resource intake well above rates found in natural habitats of bees, indicating that human activities can both decrease and increase the availability of resources in a landscape and thus reduce or enhance bee fitness. KW - urbanization KW - anthropogenic activities KW - climate factors KW - meliponines KW - resource availability Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162713 VL - 6 IS - 5 ER - TY - JOUR A1 - Seydelmann, Nora A1 - Liu, Dan A1 - Krämer, Johannes A1 - Drechsler, Christiane A1 - Hu, Kai A1 - Nordbeck, Peter A1 - Schneider, Andreas A1 - Störk, Stefan A1 - Bijnens, Bart A1 - Ertl, Georg A1 - Wanner, Christoph A1 - Weidemann, Frank T1 - High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease JF - Journal of the American Heart Association N2 - Background High‐sensitivity troponin (hs‐TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs‐TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow‐up study to assess longitudinal hs‐TNT changes relative to fibrosis and cardiomyopathy progression. Methods and Results For the prospective analysis, hs‐TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry‐associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs‐TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs‐TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56–302.59]; P=0.002); patients with elevated baseline hs‐TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1–3.3] %; follow‐up, 3.2 [2.3–4.9] %; P<0.001) and slightly elevated hs‐TNT (baseline, 44.7 [30.1–65.3] ng/L; follow‐up, 49.1 [27.6–69.5] ng/L; P=0.116) during follow‐up. Left ventricular wall thickness and EF of patients with elevated hs‐TNT were decreased during follow‐up, indicating potential cardiomyopathy progression. Conclusions hs‐TNT is an accurate, easily accessible clinical blood biomarker for detecting replacement fibrosis in patients with Fabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs‐TNT could be helpful for staging and follow‐up of Fabry patients. KW - biomarker KW - cardiomyopathy KW - fabry disease KW - myocardial fibrosis KW - troponin T Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165682 VL - 5 IS - e002839 ER - TY - JOUR A1 - Albers, Gregory W. A1 - Bernstein, Richard A. A1 - Brachmann, Johannes A1 - Camm, John A1 - Easton, J. Donald A1 - Fromm, Peter A1 - Goto, Shinya A1 - Granger, Christopher B. A1 - Hohnloser, Stefan H. A1 - Hylek, Elaine A1 - Jaffer, Amir K. A1 - Krieger, Derk W. A1 - Passman, Rod A1 - Pines, Jesse M. A1 - Reed, Shelby D. A1 - Rothwell, Peter M. A1 - Kowey, Peter R. T1 - Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report JF - Journal of the American Heart Association N2 - No abstract available. KW - anticoagulants KW - atrial fibrillation KW - diagnosis KW - electrocardiography KW - insertable cardiac monitor KW - stroke prevention Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165709 VL - 5 IS - e00294 ER - TY - JOUR A1 - Wawra, Stephan A1 - Fesel, Philipp A1 - Widmer, Heidi A1 - Timm, Malte A1 - Seibel, Jürgen A1 - Leson, Lisa A1 - Kesseler, Leona A1 - Nostadt, Robin A1 - Hilbert, Magdalena A1 - Langen, Gregor A1 - Zuccaro, Alga T1 - The fungal-specific beta-glucan-binding lectin FGB1 alters cell-wall composition and suppresses glucan-triggered immunity in plants JF - Nature Communications N2 - β-glucans are well-known modulators of the immune system in mammals but little is known about β-glucan triggered immunity in planta. Here we show by isothermal titration calorimetry, circular dichroism spectroscopy and nuclear magnetic resonance spectroscopy that the FGB1 gene from the root endophyte Piriformospora indica encodes for a secreted fungal-specific β-glucan-binding lectin with dual function. This lectin has the potential to both alter fungal cell wall composition and properties, and to efficiently suppress β-glucan-triggered immunity in different plant hosts, such as Arabidopsis, barley and Nicotiana benthamiana. Our results hint at the existence of fungal effectors that deregulate innate sensing of β-glucan in plants. KW - Effectors in plant pathology KW - Fungal host response KW - Lectins Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165945 VL - 7 ER - TY - JOUR A1 - Knorr, Johannes A1 - Sokkar, Pandian A1 - Schott, Sebastian A1 - Costa, Paolo A1 - Thiel, Walter A1 - Sander, Wolfram A1 - Sanchez-Garcia, Elsa A1 - Nuernberger, Patrick T1 - Competitive solvent-molecule interactions govern primary processes of diphenylcarbene in solvent mixtures JF - Nature Communications N2 - Photochemical reactions in solution often proceed via competing reaction pathways comprising intermediates that capture a solvent molecule. A disclosure of the underlying reaction mechanisms is challenging due to the rapid nature of these processes and the intricate identification of how many solvent molecules are involved. Here combining broadband femtosecond transient absorption and quantum mechanics/molecular mechanics simulations, we show for one of the most reactive species, diphenylcarbene, that the decision-maker is not the nearest solvent molecule but its neighbour. The hydrogen bonding dynamics determine which reaction channels are accessible in binary solvent mixtures at room temperature. In-depth analysis of the amount of nascent intermediates corroborates the importance of a hydrogen-bonded complex with a protic solvent molecule, in striking analogy to complexes found at cryogenic temperatures. Our results show that adjacent solvent molecules take the role of key abettors rather than bystanders for the fate of the reactive intermediate. KW - Reaction kinetics and dynamics KW - Photochemistry Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165954 VL - 7 ER - TY - JOUR A1 - Mitchell, Jonathan S. A1 - Li, Ni A1 - Weinhold, Niels A1 - Försti, Asta A1 - Ali, Mina A1 - van Duin, Mark A1 - Thorleifsson, Gudmar A1 - Johnson, David C. A1 - Chen, Bowang A1 - Halvarsson, Britt-Marie A1 - Gudbjartsson, Daniel F. A1 - Kuiper, Rowan A1 - Stephens, Owen W. A1 - Bertsch, Uta A1 - Broderick, Peter A1 - Campo, Chiara A1 - Einsele, Hermann A1 - Gregory, Walter A. A1 - Gullberg, Urban A1 - Henrion, Marc A1 - Hillengass, Jens A1 - Hoffmann, Per A1 - Jackson, Graham H. A1 - Johnsson, Ellinor A1 - Jöud, Magnus A1 - Kristinsson, Sigurdur Y. A1 - Lenhoff, Stig A1 - Lenive, Oleg A1 - Mellqvist, Ulf-Henrik A1 - Migliorini, Gabriele A1 - Nahi, Hareth A1 - Nelander, Sven A1 - Nickel, Jolanta A1 - Nöthen, Markus M. A1 - Rafnar, Thorunn A1 - Ross, Fiona M. A1 - da Silva Filho, Miguel Inacio A1 - Swaminathan, Bhairavi A1 - Thomsen, Hauke A1 - Turesson, Ingemar A1 - Vangsted, Annette A1 - Vogel, Ulla A1 - Waage, Anders A1 - Walker, Brian A. A1 - Wihlborg, Anna-Karin A1 - Broyl, Annemiek A1 - Davies, Faith E. A1 - Thorsteinsdottir, Unnur A1 - Langer, Christian A1 - Hansson, Markus A1 - Kaiser, Martin A1 - Sonneveld, Pieter A1 - Stefansson, Kari A1 - Morgan, Gareth J. A1 - Goldschmidt, Hartmut A1 - Hemminki, Kari A1 - Nilsson, Björn A1 - Houlston, Richard S. T1 - Genome-wide association study identifies multiple susceptibility loci for multiple myeloma JF - Nature Communications N2 - Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10−8), 6q21 (rs9372120, P=9.09 × 10−15), 7q36.1 (rs7781265, P=9.71 × 10−9), 8q24.21 (rs1948915, P=4.20 × 10−11), 9p21.3 (rs2811710, P=1.72 × 10−13), 10p12.1 (rs2790457, P=1.77 × 10−8), 16q23.1 (rs7193541, P=5.00 × 10−12) and 20q13.13 (rs6066835, P=1.36 × 10−13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development. KW - Cancer genetics KW - Genome-wide association studies KW - Myeloma Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165983 VL - 7 ER -