TY - JOUR A1 - Liu, Dan A1 - Hu, Kai A1 - Nordbeck, Peter A1 - Ertl, Georg A1 - Störk, Stefan A1 - Weidemann, Frank T1 - Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy JF - European Journal of Medical Research N2 - Despite substantial advances in the imaging techniques and pathophysiological understanding over the last decades, identification of the underlying causes of left ventricular hypertrophy by means of echocardiographic examination remains a challenge in current clinical practice. The longitudinal strain bull’s eye plot derived from 2D speckle tracking imaging offers an intuitive visual overview of the global and regional left ventricular myocardial function in a single diagram. The bull’s eye mapping is clinically feasible and the plot patterns could provide clues to the etiology of cardiomyopathies. The present review summarizes the longitudinal strain, bull’s eye plot features in patients with various cardiomyopathies and concentric left ventricular hypertrophy and the bull’s eye plot features might serve as one of the cardiac workup steps on evaluating patients with left ventricular hypertrophy. KW - speckle tracking imaging KW - bull’s eye plot KW - cardiomyopathy KW - left ventricular hypertrophy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146373 VL - 21 IS - 21 ER - TY - JOUR A1 - Westermaier, Thomas A1 - Linsenmann, Thomas A1 - Homola, György A. A1 - Loehr, Mario A1 - Stetter, Christian A1 - Willner, Nadine A1 - Ernestus, Ralf-Ingo A1 - Soymosi, Laszlo A1 - Vince, Giles H. T1 - 3D rotational fluoroscopy for intraoperative clip control in patients with intracranial aneurysms – assessment of feasibility and image quality JF - BMC Medical Imaging N2 - Background Mobile 3D fluoroscopes have become increasingly available in neurosurgical operating rooms. In this series, the image quality and value of intraoperative 3D fluoroscopy with intravenous contrast agent for the evaluation of aneurysm occlusion and vessel patency after clip placement was assessed in patients who underwent surgery for intracranial aneurysms. Materials and methods Twelve patients were included in this retrospective analysis. Prior to surgery, a 360° rotational fluoroscopy scan was performed without contrast agent followed by another scan with 50 ml of intravenous iodine contrast agent. The image files of both scans were transferred to an Apple PowerMac® workstation, subtracted and reconstructed using OsiriX® free software. The procedure was repeated after clip placement. Both image sets were compared for assessment of aneurysm occlusion and vessel patency. Results Image acquisition and contrast administration caused no adverse effects. Image quality was sufficient to follow the patency of the vessels distal to the clip. Metal artifacts reduce the assessability of the immediate vicinity of the clip. Precise image subtraction and post-processing can reduce metal artifacts and make the clip-site assessable and depict larger neck-remnants. Conclusion This technique quickly supplies images at adequate quality to evaluate distal vessel patency after aneurysm clipping. Significant aneurysm remnants may be depicted as well. As it does not require visual control of all vessels that are supposed to be evaluated intraoperatively, this technique may be complementary to other intraoperative tools like indocyanine green videoangiography and micro-Doppler, especially for the assessment of larger aneurysms. At the momentary state of this technology, it cannot replace postoperative conventional angiography. However, 3D fluoroscopy and image post-processing are young technologies. Further technical developments are likely to result in improved image quality. KW - aneurysm surgery KW - clip control KW - angiography KW - 3D fluoroscopy KW - image quality KW - intraoperative KW - vessel patency KW - contrast KW - post-processing Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146381 VL - 16 IS - 30 ER - TY - JOUR A1 - Wolf, Karen A1 - Braun, Attila A1 - Haining, Elizabeth J. A1 - Tseng, Yu-Lun A1 - Kraft, Peter A1 - Schuhmann, Michael K. A1 - Gotru, Sanjeev K. A1 - Chen, Wenchun A1 - Hermanns, Heike M. A1 - Stoll, Guido A1 - Lesch, Klaus-Peter A1 - Nieswandt, Bernhard T1 - Partially Defective Store Operated Calcium Entry and Hem(ITAM) Signaling in Platelets of Serotonin Transporter Deficient Mice JF - PLoS One N2 - Background Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A). Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation. Objective To identify the molecular composite of the 5-HT uptake system in platelets and elucidate the role of platelet released 5-HT in thrombosis and ischemic stroke. Methods: 5-HT transporter knockout mice (5Htt\(^{-/-}\)) were analyzed in different in vitro and in vivo assays and in a model of ischemic stroke. Results In 5Htt\(^{-/-}\) platelets, 5-HT uptake from the blood was completely abolished and agonist-induced Ca2+ influx through store operated Ca\(^{2+}\) entry (SOCE), integrin activation, degranulation and aggregation responses to glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) were reduced. These observed in vitro defects in 5Htt\(^{-/-}\) platelets could be normalized by the addition of exogenous 5-HT. Moreover, reduced 5-HT levels in the plasma, an increased bleeding time and the formation of unstable thrombi were observed ex vivo under flow and in vivo in the abdominal aorta and carotid artery of 5Htt\(^{-/-}\) mice. Surprisingly, in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke 5Htt\(^{-/-}\) mice showed nearly normal infarct volume and the neurological outcome was comparable to control mice. Conclusion Although secreted platelet 5-HT does not appear to play a crucial role in the development of reperfusion injury after stroke, it is essential to amplify the second phase of platelet activation through SOCE and plays an important role in thrombus stabilization. KW - platelets KW - serotonin KW - integrins KW - blood flow KW - collagens KW - platelet activation KW - platelet aggregation KW - ischemic stroke Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146399 VL - 11 IS - 1 ER - TY - JOUR A1 - Zhu, Min A1 - Shabala, Lana A1 - Cuin, Tracey A A1 - Huang, Xin A1 - Zhou, Meixue A1 - Munns, Rana A1 - Shabala, Sergey T1 - Nax loci affect SOS1-like Na\(^{+}\)/H\(^{+}\) exchanger expression and activity in wheat JF - Journal of Experimental Botany N2 - Salinity stress tolerance in durum wheat is strongly associated with a plant’s ability to control Na\(^{+}\) delivery to the shoot. Two loci, termed Nax1 and Nax2, were recently identified as being critical for this process and the sodium transporters HKT1;4 and HKT1;5 were identified as the respective candidate genes. These transporters retrieve Na\(^{+}\) from the xylem, thus limiting the rates of Na\(^{+}\) transport from the root to the shoot. In this work, we show that the Nax loci also affect activity and expression levels of the SOS1-like Na\(^{+}\)/H\(^{+}\) exchanger in both root cortical and stelar tissues. Net Na\(^{+}\) efflux measured in isolated steles from salt-treated plants, using the non-invasive ion flux measuring MIFE technique, decreased in the sequence: Tamaroi (parental line)>Nax1=Nax2>Nax1:Nax2 lines. This efflux was sensitive to amiloride (a known inhibitor of the Na\(^{+}\)/H\(^{+}\) exchanger) and was mirrored by net H\(^{+}\) flux changes. TdSOS1 relative transcript levels were 6–10-fold lower in Nax lines compared with Tamaroi. Thus, it appears that Nax loci confer two highly complementary mechanisms, both of which contribute towards reducing the xylem Na\(^{+}\) content. One enhances the retrieval of Na\(^{+}\) back into the root stele via HKT1;4 or HKT1;5, whilst the other reduces the rate of Na\(^{+}\) loading into the xylem via SOS1. It is suggested that such duality plays an important adaptive role with greater versatility for responding to a changing environment and controlling Na\(^{+}\) delivery to the shoot. KW - HKT transporter KW - potassium KW - salinity stress KW - sequestration KW - sodium KW - xylem loading Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150236 VL - 67 IS - 3 ER - TY - JOUR A1 - Neuderth, Silke A1 - Schwarz, Betje A1 - Gerlich, Christian A1 - Schuler, Michael A1 - Markus, Miriam A1 - Bethge, Matthias T1 - Work-related medical rehabilitation in patients with musculoskeletal disorders: the protocol of a propensity score matched effectiveness study (EVA-WMR, DRKS00009780) JF - BMC Public Health N2 - Background Musculoskeletal disorders are one of the most important causes of work disability. Various rehabilitation services and return-to-work programs have been developed in order to reduce sickness absence and increase sustainable return-to-work. As the effects of conventional medical rehabilitation programs on sickness absence duration were shown to be slight, work-related medical rehabilitation programs have been developed and tested. While such studies proved the efficacy of work-related medical rehabilitation compared with conventional medical rehabilitation in well-conducted randomized controlled trials, its effectiveness under real-life conditions has yet to be proved. Methods/Design The cohort study will be performed under real-life conditions with two parallel groups. Participants will receive either a conventional or a work-related medical rehabilitation program. Propensity score matching will be used to identify controls that are comparable to treated work-related medical rehabilitation patients. Over a period of three months, about 18,000 insured patients with permission to undergo a musculoskeletal rehabilitation program will be contacted. Of these, 15,000 will receive a conventional and 3,000 a work-related medical rehabilitation. We expect a participation rate of 40 % at baseline. Patients will be aged 18 to 65 years and have chronic musculoskeletal disorders, usually back pain. The control group will receive a conventional medical rehabilitation program without any explicit focus on work, work ability and return to work in diagnostics and therapy. The intervention group will receive a work-related medical rehabilitation program that in addition to common rehabilitation treatments contains 11 to 25 h of work-related treatment modules. Follow-up data will be assessed three and ten months after patients’ discharge from the rehabilitation center. Additionally, department characteristics will be assessed and administrative data records used. The primary outcomes are sick leave duration, stable return to work and subjective work ability. Secondary outcomes cover several dimensions of health, functioning and coping strategies. Discussion This study will determine the relative effectiveness of a complex, newly implemented work-related rehabilitation strategy for patients with musculoskeletal disorders. KW - propensity score matching KW - work-related medical rehabilitation KW - effectiveness KW - work ability KW - return to work Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150015 VL - 16 IS - 804 ER - TY - JOUR A1 - Borkert, Franziska T1 - BibScout – der mobile Auskunftsdienst an der UB Würzburg JF - BuB. Forum Bibliothek und Information N2 - Seit dem Wintersemester 2014/15 setzt die Universitätsbibliothek (UB) Würzburg in der Zentralbibliothek sogenannte BibScouts ein. Das sind studentische Hilfskräfte, die die Nutzerinnen und Nutzer der Bibliothek – hauptsächlich Studierende – beim Kopieren, Drucken, Scannen und beim Auffinden von Büchern unterstützen. Die BibScouts haben keinen festen Standort, sondern helfen direkt vor Ort, an den Kopierern, Computern, Scan-Stationen und in den Lesesälen. Erkennbar sind sie an blauen Westen mit dem Logo der UB Würzburg sowie dem Hinweis »Fragen? Ich helfe weiter!« auf dem Rücken. Die BibScouts, die nur während der Vorlesungszeit eingesetzt werden, entlasten durch ihre Anwesenheit das bibliothekarische Personal an der Informationstheke. KW - mobiler Auskunftsdienst KW - peer-to-peer Auskunftsdienst KW - roving reference KW - roaming reference KW - Auskunftsdienst KW - Universitätsbibliothek Würzburg Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148145 UR - http://b-u-b.de/archiv/ VL - 68 IS - 12 ER - TY - JOUR A1 - Schindele, Andreas A1 - Borzì, Alfio T1 - Proximal Methods for Elliptic Optimal Control Problems with Sparsity Cost Functional JF - Applied Mathematics N2 - First-order proximal methods that solve linear and bilinear elliptic optimal control problems with a sparsity cost functional are discussed. In particular, fast convergence of these methods is proved. For benchmarking purposes, inexact proximal schemes are compared to an inexact semismooth Newton method. Results of numerical experiments are presented to demonstrate the computational effectiveness of proximal schemes applied to infinite-dimensional elliptic optimal control problems and to validate the theoretical estimates. KW - semismooth Newton method KW - optimal control KW - elliptic PDE KW - nonsmooth optimization KW - proximal method Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145850 VL - 7 IS - 9 ER - TY - JOUR A1 - Dietl, Sebastian A1 - Schwinn, Stefanie A1 - Dietl, Susanne A1 - Riedl, Simone A1 - Deinlein, Frank A1 - Rutkowski, Stefan A1 - von Bueren, Andre O. A1 - Krauss, Jürgen A1 - Schweitzer, Tilmann A1 - Vince, Giles H. A1 - Picard, Daniel A1 - Eyrich, Matthias A1 - Rosenwald, Andreas A1 - Ramaswamy, Vijay A1 - Taylor, Michael D. A1 - Remke, Marc A1 - Monoranu, Camelia M. A1 - Beilhack, Andreas A1 - Schlegel, Paul G. A1 - Wölfl, Matthias T1 - MB3W1 is an orthotopic xenograft model for anaplastic medulloblastoma displaying cancer stem cell- and Group 3-properties JF - BMC Cancer N2 - Background Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup. Methods We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma. Results Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture. Conclusions This model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma. KW - cancer stem cells KW - anaplastic medulloblastoma KW - group 3 KW - orthotopic xenograft KW - animal model KW - brain tumor KW - children Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145877 VL - 16 IS - 115 ER - TY - JOUR A1 - Peck, Barrie A1 - Schug, Zachary T. A1 - Zhang, Qifeng A1 - Dankworth, Beatrice A1 - Jones, Dylan T. A1 - Smethurst, Elizabeth A1 - Patel, Rachana A1 - Mason, Susan A1 - Jian, Ming A1 - Saunders, Rebecca A1 - Howell, Michael A1 - Mitter, Richard A1 - Spencer-Dene, Bradley A1 - Stamp, Gordon A1 - McGarry, Lynn A1 - James, Daniel A1 - Shanks, Emma A1 - Aboagye, Eric O. A1 - Critchlow, Susan E. A1 - Leung, Hing Y. A1 - Harris, Adrian L. A1 - Wakelam, Michael J. O. A1 - Gottlieb, Eyal A1 - Schulze, Almut T1 - Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments JF - Cancer & Metabolism N2 - Background Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets. Results Using functional genomics, we identified stearoyl-CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty acids, as essential in breast and prostate cancer cells. SCD inhibition altered cellular lipid composition and impeded cell viability in the absence of exogenous lipids. SCD inhibition also altered cardiolipin composition, leading to the release of cytochrome C and induction of apoptosis. Furthermore, SCD was required for the generation of poly-unsaturated lipids in cancer cells grown in spheroid cultures, which resemble those found in tumour tissue. We also found that SCD mRNA and protein expression is elevated in human breast cancers and predicts poor survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts efficiently blocked tumour growth and significantly increased animal survival. Conclusions Our data implicate lipid desaturation as an essential process for cancer cell survival and suggest that targeting SCD could efficiently limit tumour expansion, especially under the metabolically compromised conditions of the tumour microenvironment. KW - SCD KW - lipidomics KW - prostate cancer KW - breast cancer KW - lipid desaturation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145905 VL - 4 IS - 6 ER - TY - JOUR A1 - Schuberth, Florian A1 - Henseler, Jörg A1 - Dijkstra, Theo K. T1 - Partial least squares path modeling using ordinal categorical indicators JF - Quality & Quantity N2 - This article introduces a new consistent variance-based estimator called ordinal consistent partial least squares (OrdPLSc). OrdPLSc completes the family of variance-based estimators consisting of PLS, PLSc, and OrdPLS and permits to estimate structural equation models of composites and common factors if some or all indicators are measured on an ordinal categorical scale. A Monte Carlo simulation (N =500) with different population models shows that OrdPLSc provides almost unbiased estimates. If all constructs are modeled as common factors, OrdPLSc yields estimates close to those of its covariance-based counterpart, WLSMV, but is less efficient. If some constructs are modeled as composites, OrdPLSc is virtually without competition. KW - polychoric correlation KW - composites KW - common factors KW - ordinal categorical indicators KW - consistent partial least squares KW - structural equation models Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144016 ER - TY - JOUR A1 - Walter, T. A1 - Collenburg, L. A1 - Japtok, L. A1 - Kleuser, B. A1 - Schneider-Schaulies, S. A1 - Müller, N. A1 - Becam, J. A1 - Schubert-Unkmeir, A. A1 - Kong, J. N. A1 - Bieberich, E. A1 - Seibel, J. T1 - Incorporation and visualization of azido-functionalized N-oleoyl serinol in Jurkat cells, mouse brain astrocytes, 3T3 fibroblasts and human brain microvascular endothelial cells JF - Chemical Communications N2 - The synthesis and biological evaluation of azido-N-oleoyl serinol is reported. It mimicks biofunctional lipid ceramides and has shown to be capable of click reactions for cell membrane imaging in Jurkat and human brain microvascular endothelial cells. KW - Ceramide KW - Apoptosis KW - Golgi KW - N-oleoyl serinol KW - Jurkat cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191263 VL - 52 IS - 55 ER - TY - JOUR A1 - Flegler, Andreas A1 - Schneider, Michael A1 - Prieschl, Johannes A1 - Stevens, Ralph A1 - Vinnay, Thomas A1 - Mandel, Karl T1 - Continuous flow synthesis and cleaning of nano layered double hydroxides and the potential of the route to adjust round or platelet nanoparticle morphology JF - RSC Advances N2 - Here, we report a continuous flow synthesis of nano LDH, comprising a continuous precipitation process using static mixers and followed by an immediate cleaning process via a semi-continuous centrifuge to obtain the final product in one-go. Via this synthesis setup, it is possible to independently vary the concentrations of the reactants during precipitation and at the same time ensure constant reaction conditions and an immediate "quenching" of the precipitate due to "on the flow"-washing. We found that this paves the way to adjust the synthesis parameters in a way that the final morphology of the nano-LDH particles can be controlled to be either round or platelet-like. KW - MgAl LDH KW - nano LDH KW - static mixer KW - synthesis process Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191305 VL - 6 IS - 62 ER - TY - JOUR A1 - Emmert, M. A1 - Witzel, P. A1 - Heinrich, D. T1 - Challenges in tissue engineering - towards cell control inside artificial scaffolds JF - Soft Matter N2 - Control of living cells is vital for the survival of organisms. Each cell inside an organism is exposed to diverse external mechano-chemical cues, all coordinated in a spatio-temporal pattern triggering individual cell functions. This complex interplay between external chemical cues and mechanical 3D environments is translated into intracellular signaling loops. Here, we describe how external mechano-chemical cues control cell functions, especially cell migration, and influence intracellular information transport. In particular, this work focuses on the quantitative analysis of (1) intracellular vesicle transport to understand intracellular state changes in response to external cues, (2) cellular sensing of external chemotactic cues, and (3) the cells' ability to migrate in 3D structured environments, artificially fabricated to mimic the 3D environment of tissue in the human body. KW - chemotaxis KW - intracellular transport KW - cytoskeleton dynamics KW - adhesion KW - diffusion Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191341 VL - 12 IS - 19 ER - TY - JOUR A1 - Kirchner, Felix A1 - Dittrich, Marco A1 - Beckenbauer, Phillip A1 - Nöth, Maximilian T1 - OCR bei Inkunabeln – Offizinspezifischer Ansatz der Universitätsbibliothek Würzburg T1 - OCR processing of incunabula: printshop-specific approach of the University Library of Würzburg JF - ABI Technik N2 - Im Rahmen des BMBF-geförderten Projekts KALLIMACHOS an der Universität Würzburg soll unter anderem die Textgrundlage für digitale Editionen per OCR gewonnen werden. Das Bearbeitungskorpus besteht aus deutschen, französischen und lateinischen Inkunabeln. Dieser Artikel zeigt, wie man mit bereits heute existierenden Methoden und Programmen den Problemen bei der OCR von Inkunabeln entgegentreten kann. Hierzu wurde an der Universitätsbibliothek Würzburg ein Verfahren erprobt, mit dem auf ausgewählten Werken einer Druckerwerkstatt bereits Zeichengenauigkeiten von bis zu 95 Prozent und Wortgenauigkeiten von bis zu 73 Prozent erzielt werden. KW - OCR KW - Tesseract KW - Inkunabel KW - OCR KW - Tesseract KW - Incunabula Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194002 SN - 2191-4664 SN - 0720-6763 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 36 IS - 3 ER - TY - JOUR A1 - Schmidt, Hans-Günter T1 - Kallimachos: Digital Humanities als Auftrag der Universitätsbibliothek Würzburg T1 - Kallimachos: Digital humanities as a university library’s task in Würzburg JF - ABI Technik N2 - KALLIMACHOS baut an der Universitätsbibliothek Würzburg ein Digital-Humanitites-Zentrum mit den Arbeitsschwerpunkten OCR, digitale Edition, Textmining und quantitative Analyse auf. Das Zentrum bietet eine technische und soziale Infrastruktur, die Geisteswissenschaftler bei der Beantwortung von Forschungsfragen unterstützt und innovative Werkzeuge, Methoden, prototypische Arbeitsabläufe und Dienste entwickelt. In sechs Beispielprojekten aus Papyrologie, Geschichte, Philologie, Philosophie und Pädagogik werden die Neuentwicklungen erprobt, die Fruchtbarkeit der neuen Verfahren vermittelt und Bausteine für ein künftiges Forschungsdatenmanagement geschaffen. Das BMBF unterstützt den Aufbau des Zentrums bis Ende 2017 im Rahmen der Förderlinie „eHumanities“. N2 - Kallimachos is to set up the Würzburg Center for Digital Humanities. The new center with its special focus on OCR, digital edition, natural language processing, and text analytics will provide a technical and social infrastructure to support research in the humanities by offering a wide portfolio of digital services and by developing innovative tools, workflows, and digital methodologies for the entire process chain of text-oriented research. Six model projects from disciplines as diverse as papyrology, history, German, English, French, Latin and Ancient Greek philology, philosophy, and education illustrate the capability and usefulness of the project’s assets. Kallimachos is recipient of a grant from Germany’s Federal Ministry of Education and Research (line of funding “eHumanities”, 2014–2017). KW - Digitalisierung KW - Forschungsinfrastruktur KW - Digital Humanities KW - Digitization KW - Research Infrastructure KW - Digital Humanities Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194011 SN - 2191-4664 SN - 0720-6763 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 36 IS - 3 ER - TY - JOUR A1 - Preuß, Tamina T1 - Das Klageerzwingungsverfahren: Ein Überblick über prüfungsrelevante Fragen JF - JURA - Juristische Ausbildung N2 - Kein Abstract verfügbar KW - Strafrecht Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194040 SN - 1612-7021 SN - 0170-1452 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 2016 IS - 38 ER - TY - JOUR A1 - Beck, Lukas T1 - Zur Funktionsweise der Prokura als handelsrechtliche Vollmacht JF - JURA - Juristische Ausbildung N2 - Kein Abstract verfügbar. KW - Prokura Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195109 SN - 1612-7021 SN - 0170-1452 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 38 IS - 9 PB - De Gruyter ER - TY - JOUR A1 - Schmahl, Stefanie A1 - Jung, Florian T1 - Die Unionsbürgerschaft: Ein komplexes Rechtsinstitut mit weitreichenden Folgen JF - JURA - Juristische Ausbildung N2 - Kein Abstract verfügbar. KW - Unionsbürgerschaft Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195119 SN - 1612-7021 SN - 0170-1452 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 2016 IS - 11 ER - TY - JOUR A1 - Fröhlich, Andrea T1 - Discussion Report: Formation of Companies JF - European Company and Financial Law Review N2 - No abstract available. KW - discussion report Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194468 SN - 1613-2556 SN - 1613-2548 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 - 13 IS - 2 ER - TY - JOUR A1 - Schmidt, Lena T1 - Discussions Report: Reorganization of Companies JF - European Company and Financial Law Review N2 - No abstract available. KW - discussion report Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194479 SN - 1613-2556 SN - 1613-2548 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 - 13 IS - 2 ER - TY - JOUR A1 - Teichmann, Christoph T1 - Corporate Restructuring under the EMCA JF - European Company and Financial Law Review N2 - No abstract available. KW - corporate restructuring Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194488 SN - 1613-2556 SN - 1613-2548 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 - 13 IS - 2 SP - 277 EP - 300 ER - TY - JOUR A1 - Clauss, Kersten A1 - Yan, Huimin A1 - Kuenzer, Claudia T1 - Mapping Paddy Rice in China in 2002, 2005, 2010 and 2014 with MODIS Time Series JF - Remote Sensing N2 - Rice is an important food crop and a large producer of green-house relevant methane. Accurate and timely maps of paddy fields are most important in the context of food security and greenhouse gas emission modelling. During their life-cycle, rice plants undergo a phenological development that influences their interaction with waves in the visible light and infrared spectrum. Rice growth has a distinctive signature in time series of remotely-sensed data. We used time series of MODIS (Moderate Resolution Imaging Spectroradiometer) products MOD13Q1 and MYD13Q1 and a one-class support vector machine to detect these signatures and classify paddy rice areas in continental China. Based on these classifications, we present a novel product for continental China that shows rice areas for the years 2002, 2005, 2010 and 2014 at 250-m resolution. Our classification has an overall accuracy of 0.90 and a kappa coefficient of 0.77 compared to our own reference dataset for 2014 and correlates highly with rice area statistics from China’s Statistical Yearbooks (R2 of 0.92 for 2010, 0.92 for 2005 and 0.90 for 2002). Moderate resolution time series analysis allows accurate and timely mapping of rice paddies over large areas with diverse cropping schemes. KW - agriculture KW - rice KW - China KW - MODIS KW - time series KW - SVM KW - OCSVM KW - change detection Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180557 VL - 8 IS - 5 ER - TY - JOUR A1 - Tomasek, Stefan T1 - Frauen- und Männerrollen in mittelhochdeutscher Kreuzzugslyrik JF - Das Mittelalter N2 - This article focuses on the effects that crusade motives woven into Middle High German courtly lovesongs have on gender binarism in these text. The analysis draws on two examples from the first period of Middle High German crusade poetry: Friedrich von Hausen, ‘Si darf mich des zîhen niet’ and Albrecht von Johansdorf, ‘Guote liute, holt die gâbe’. I examine whether the relation between lady and male speaker is altered by the crusader’s divine service and whether this affects the gender binarism in the songs. The article concludes with a discussion of the repercussions gender binarism has on the concepts of crusading in the two texts. KW - German crusade poetry KW - Friedrich von Hausen KW - Albrecht von Johansdorf KW - deutsche Kreuzzugslyrik KW - Friedrich von Hausen KW - Albrecht von Johansdorf Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193356 SN - 2196-6869 SN - 0949-0345 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 21 IS - 1 ER - TY - JOUR A1 - Wächtler, Maria A1 - Kübel, Joachim A1 - Barthelmes, Kevin A1 - Winter, Andreas A1 - Schmiedel, Alexander A1 - Pascher, Torbjörn A1 - Lambert, Christoph A1 - Schubert, Ulrich S. A1 - Dietzek, Benjamin T1 - Energy transfer and formation of long-lived \(^3\)MLCT states in multimetallic complexes with extended highly conjugated bis-terpyridyl ligands JF - Physical Chemistry Chemical Physics N2 - Multimetallic complexes with extended and highly conjugated bis-2,2':6',2''-terpyridyl bridging ligands, which present building blocks for coordination polymers, are investigated with respect to their ability to act as light-harvesting antennae. The investigated species combine Ru(II)- with Os(II)- and Fe(II)-terpyridyl chromophores, the latter acting as energy sinks. Due to the extended conjugated system the ligands are able to prolong the lifetime of the \(^3\)MLCT states compared to unsubstituted terpyridyl species by delocalization and energetic stabilization of the \(^3\)MLCT states. This concept is applied for the first time to Fe(II) terpyridyl species and results in an exceptionally long lifetime of 23 ps for the Fe(II) \(^3\)MLCT state. While partial energy (>80%) transfer is observed between the Ru(II) and Fe(II) centers with a time-constant of 15 ps, excitation energy is transferred completely from the Ru(II) to the Os(II) center within the first 200 fs after excitation. KW - polypyridyl complexes KW - bis-terpyridyl ligands KW - multimetallic complexes KW - metal-to-ligand charge transfer (MLCT) KW - RU-(II) complexes KW - Ru(II)–Fe(II)–Ru(II) complex Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191041 VL - 18 IS - 4 ER - TY - JOUR A1 - Grimm, Jonathan B. A1 - Klein, Teresa A1 - Kopek, Benjamin G. A1 - Shtengel, Gleb A1 - Hess, Harald F. A1 - Sauer, Markus A1 - Lavis, Luke D. T1 - Synthesis of a far-red photoactivatable silicon-containing rhodamine for super-resolution microscopy JF - Angewandte Chemie International Edition N2 - The rhodamine system is a flexible framework for building small‐molecule fluorescent probes. Changing N‐substitution patterns and replacing the xanthene oxygen with a dimethylsilicon moiety can shift the absorption and fluorescence emission maxima of rhodamine dyes to longer wavelengths. Acylation of the rhodamine nitrogen atoms forces the molecule to adopt a nonfluorescent lactone form, providing a convenient method to make fluorogenic compounds. Herein, we take advantage of all of these structural manipulations and describe a novel photoactivatable fluorophore based on a Si‐containing analogue of Q‐rhodamine. This probe is the first example of a “caged” Si‐rhodamine, exhibits higher photon counts compared to established localization microscopy dyes, and is sufficiently red‐shifted to allow multicolor imaging. The dye is a useful label for super‐resolution imaging and constitutes a new scaffold for far‐red fluorogenic molecules. KW - fluorophore KW - microscopy KW - photoactivation KW - Si-rhodamine KW - super-resolution imaging Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191069 VL - 55 IS - 5 ER - TY - JOUR A1 - Kar, Haridas A1 - Gehrig, Dominik W. A1 - Allampally, Naveen Kumar A1 - Fernández, Gustavo A1 - Laquai, Frédéric A1 - Ghosh, Suhrit T1 - Cooperative supramolecular polymerization of an amine-substituted naphthalene-diimide and its impact on excited state photophysical properties JF - Chemical Science N2 - A donor-acceptor-donor (D-A-D) type naphthalene-diimide (NDI-H) chromophore exhibits highly cooperative J-aggregation leading to nanotubular self-assembly and gelation in n-decane, as demonstrated by UV/Vis, FT-IR, photoluminescence and microscopy studies. Analysis of temperature-dependent UV/Vis spectra using the nucleation-elongation model and FT-IR data reveals the molecular origin of the cooperative nature of the self-assembly. The supramolecular polymerization is initiated by H-bonding up to a degree of polymerization similar to 20-25, which in a subsequent elongation step promotes J-aggregation in orthogonal direction leading to possibly a sheet-like structure that eventually produces nanotubes. Time-resolved fluorescence and absorption measurements demonstrate that such a tubular assembly enables very effective delocalization of excited states resulting in a remarkably prolonged excited state lifetime. KW - nanotube KW - supramolecular polymerization KW - NDI-H KW - UV/Vis spectroscopy KW - FT-IR spectroscopy KW - transient absorption KW - nucleation-elongation model Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191459 VL - 7 IS - 2 ER - TY - JOUR A1 - Zhu, Min A1 - Shabala, Lana A1 - Cuin, Tracey A. A1 - Huang, Xin A1 - Zhou, Meixue A1 - Munns, Rana A1 - Shabala, Sergey T1 - Nax loci affect SOS1-like Na\(^+\)/H\(^+\) exchanger expression and activity in wheat JF - Journal of Experimental Botany N2 - Salinity stress tolerance in durum wheat is strongly associated with a plant's ability to control Na\(^+\) delivery to the shoot. Two loci, termed Nax1 and Nax2, were recently identified as being critical for this process and the sodium transporters HKT1;4 and HKT1; 5 were identified as the respective candidate genes. These transporters retrieve Na\(^+\) from the xylem, thus limiting the rates of Na\(^+\) transport from the root to the shoot. In this work, we show that the Nax loci also affect activity and expression levels of the SOS1-like Na\(^+\)/H\(^+\) exchanger in both root cortical and stelar tissues. Net Na\(^+\) efflux measured in isolated steles from salt-treated plants, using the non-invasive ion flux measuring MIFE technique, decreased in the sequence: Tamaroi (parental line)>Nax1=Nax2>Nax1:Nax2 lines. This efflux was sensitive to amiloride (a known inhibitor of the Na\(^+\)/H\(^+\) exchanger) and was mirrored by net H\(^+\) flux changes. TdSOS1 relative transcript levels were 6-10-fold lower in Nax lines compared with Tamaroi. Thus, it appears that Nax loci confer two highly complementary mechanisms, both of which contribute towards reducing the xylem Na\(^+\) content. One enhances the retrieval of Na\(^+\) back into the root stele via HKT1;4 or HKT1;5, whilst the other reduces the rate of Na\(^+\) loading into the xylem via SOS1. It is suggested that such duality plays an important adaptive role with greater versatility for responding to a changing environment and controlling Na\(^+\) delivery to the shoot. KW - HKT transporter KW - potassium KW - salinity stress KW - sequestration KW - sodium KW - xylem loading Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190908 VL - 67 IS - 3 ER - TY - JOUR A1 - Adrián-Martínez, S. A1 - Ageron, M. A1 - Aharonian, F. A1 - Aiello, S. A1 - Albert, A. A1 - Ameli, F. A1 - Annasontzis, E. A1 - Andre, M. A1 - Androulakis, G. A1 - Anghinolfi, M. A1 - Anton, G. A1 - Ardid, M. A1 - Avgitas, T. A1 - Barbarino, G. A1 - Baret, B. A1 - Barrios-Martí, J. A1 - Belhorma, B. A1 - Belias, A. A1 - Berbee, A. A1 - van den Berg, A. A1 - Bertin, V. A1 - Beurthey, S. A1 - van Beeveren, V. A1 - Beverini, N. A1 - Biagi, S. A1 - Biagioni, A. A1 - Billault, M. A1 - Bondì, M. A1 - Bormuth, R. A1 - Bouhadef, B. A1 - Bourlis, G. A1 - Bourret, S. A1 - Boutonnet, C. A1 - Bouwhuis, M. A1 - Bozza, C. A1 - Bruijn, R. A1 - Brunner, J. A1 - Buis, E. A1 - Busto, J. A1 - Cacopardo, G. A1 - Caillat, L. A1 - Calmai, M. A1 - Calvo, D. A1 - Capone, A. A1 - Caramete, L. A1 - Cecchini, S. A1 - Celli, S. A1 - Champion, C. A1 - Cherkaoui El Moursli, R. A1 - Cherubini, S. A1 - Chiarusi, T. A1 - Circella, M. A1 - Classen, L. A1 - Cocimano, R. A1 - Coelho, J. A. B. A1 - Coleiro, A. A1 - Colonges, S. A1 - Coniglione, R. A1 - Cordelli, M. A1 - Cosquer, A. A1 - Coyle, P. A1 - Creusot, A. A1 - Cuttone, G. A1 - D'Amico, A. A1 - De Bonis, G. A1 - De Rosa, G. A1 - De Sio, C. A1 - Di Capua, F. A1 - Di Palma, I. A1 - Díaz García, A. F. A1 - Distefano, C. A1 - Donzaud, C. A1 - Dornic, D. A1 - Dorosti-Hasankiadeh, Q. A1 - Drakopoulou, E. A1 - Drouhin, D. A1 - Drury, L. A1 - Durocher, M. A1 - Eberl, T. A1 - Eichie, S. A1 - van Eijk, D. A1 - El Bojaddaini, I. A1 - El Khayati, N. A1 - Elsaesser, D. A1 - Enzenhöfer, A. A1 - Fassi, F. A1 - Favali, P. A1 - Fermani, P. A1 - Ferrara, G. A1 - Filippidis, C. A1 - Frascadore, G. A1 - Fusco, L. A. A1 - Gal, T. A1 - Galatà, S. A1 - Garufi, F. A1 - Gay, P. A1 - Gebyehu, M. A1 - Giordano, V. A1 - Gizani, N. A1 - Gracia, R. A1 - Graf, K. A1 - Grégoire, T. A1 - Grella, G. A1 - Habel, R. A1 - Hallmann, S. A1 - van Haren, H. A1 - Harissopulos, S. A1 - Heid, T. A1 - Heijboer, A. A1 - Heine, E. A1 - Henry, S. A1 - Hernández-Rey, J. J. A1 - Hevinga, M. A1 - Hofestädt, J. A1 - Hugon, C. M. F. A1 - Illuminati, G. A1 - James, C. W. A1 - Jansweijer, P. A1 - Jongen, M. A1 - de Jong, M. A1 - Kadler, M. A1 - Kalekin, O. A1 - Kappes, A. A1 - Katz, U. F. A1 - Keller, P. A1 - Kieft, G. A1 - Kießling, D. A1 - Koffeman, E. N. A1 - Kooijman, P. A1 - Kouchner, A. A1 - Kulikovskiy, V. A1 - Lahmann, R. A1 - Lamare, P. A1 - Leisos, A. A1 - Leonora, E. A1 - Lindsey Clark, M. A1 - Liolios, A. A1 - Llorenz Alvarez, C. D. A1 - Lo Presti, D. A1 - Löhner, H. A1 - Lonardo, A. A1 - Lotze, M. A1 - Loucatos, S. A1 - Maccioni, E. A1 - Mannheim, K. A1 - Margiotta, A. A1 - Marinelli, A. A1 - Mariş, O. A1 - Markou, C. A1 - Martínez-Mora, J. A. A1 - Martini, A. A1 - Mele, R. A1 - Melis, K. W. A1 - Michael, T. A1 - Migliozzi, P. A1 - Migneco, E. A1 - Mijakowski, P. A1 - Miraglia, A. A1 - Mollo, C. M. A1 - Mongelli, M. A1 - Morganti, M. A1 - Moussa, A. A1 - Musico, P. A1 - Musumeci, M. A1 - Navas, S. A1 - Nicoleau, C. A. A1 - Olcina, I. A1 - Olivetto, C. A1 - Orlando, A. A1 - Papaikonomou, A. A1 - Papaleo, R. A1 - Păvălaş, G. E. A1 - Peek, H. A1 - Pellegrino, C. A1 - Perrina, C. A1 - Pfutzner, M. A1 - Piattelli, P. A1 - Pikounis, K. A1 - Poma, G. E. A1 - Popa, V. A1 - Pradier, T. A1 - Pratolongo, F. A1 - Pühlhofer, G. A1 - Pulvirenti, S. A1 - Quinn, L. A1 - Racca, C. A1 - Raffaelli, F. A1 - Randazzo, N. A1 - Rapidis, P. A1 - Razis, P. A1 - Real, D. A1 - Resvanis, L. A1 - Reubelt, J. A1 - Riccobene, G. A1 - Rossi, C. A1 - Rovelli, A. A1 - Saldaña, M. A1 - Salvadori, I. A1 - Samtleben, D. F. E. A1 - Sánchez García, A. A1 - Sánchez Losa, A. A1 - Sanguineti, M. A1 - Santangelo, A. A1 - Santonocito, D. A1 - Sapienza, P. A1 - Schimmel, F. A1 - Schmelling, J. A1 - Sciacca, V. A1 - Sedita, M. A1 - Seitz, T. A1 - Sgura, I. A1 - Simeone, F. A1 - Siotis, I. A1 - Sipala, V. A1 - Spisso, B. A1 - Spurio, M. A1 - Stavropoulos, G. A1 - Steijger, J. A1 - Stellacci, S. M. A1 - Stransky, D. A1 - Taiuti, M. A1 - Tayalati, Y. A1 - Tézier, D. A1 - Theraube, S. A1 - Thompson, L. A1 - Timmer, P. A1 - Tönnis, C. A1 - Trasatti, L. A1 - Trovato, A. A1 - Tsirigotis, A. A1 - Tzamarias, S. A1 - Tzamariudaki, E. A1 - Vallage, B. A1 - Van Elewyk, V. A1 - Vermeulen, J. A1 - Vicini, P. A1 - Viola, S. A1 - Vivolo, D. A1 - Volkert, M. A1 - Voulgaris, G. A1 - Wiggers, L. A1 - Wilms, J. A1 - de Wolf, E. A1 - Zachariadou, K. A1 - Zornoza, J. D. A1 - Zúñiga, J. T1 - Letter of intent for KM3NeT 2.0 JF - Journal of Physics G-Nuclear and Particle Physics N2 - The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and KW - neutrino astronomy KW - eutrino physics KW - deep sea neutrino telescope KW - neutrino mass hierarchy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188050 VL - 43 IS - 8 ER - TY - JOUR A1 - Dinnes, Jacqueline A1 - Bancos, Irina A1 - di Ruffano, Lavinia Ferrante A1 - Chortis, Vasileios A1 - Davenport, Clare A1 - Bayliss, Susan A1 - Sahdev, Anju A1 - Guest, Peter A1 - Fassnacht, Martin A1 - Deeks, Jonathan J A1 - Arlt, Wiebke T1 - Imaging for the diagnosis of malignancy in incidentally discovered adrenal masses: a systematic review and meta-analysis JF - European Journal of Endocrinology N2 - Objective: Adrenal masses are incidentally discovered in 5% of CT scans. In 2013/2014, 81 million CT examinations were undertaken in the USA and 5 million in the UK. However, uncertainty remains around the optimal imaging approach for diagnosing malignancy. We aimed to review the evidence on the accuracy of imaging tests for differentiating malignant from benign adrenal masses. Design: A systematic review and meta-analysis was conducted. Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index, and ZETOC (January 1990 to August 2015). We included studies evaluating the accuracy of CT, MRI, or F-18-fluoro-deoxyglucose (FDG)-PET compared with an adequate histological or imaging-based follow-up reference standard. Results: We identified 37 studies suitable for inclusion, after screening 5469 references and 525 full-text articles. Studies evaluated the accuracy of CT (n = 16), MRI (n = 15), and FDG-PET (n = 9) and were generally small and at high or unclear risk of bias. Only 19 studies were eligible for meta-analysis. Limited data suggest that CT density >10 HU has high sensitivity for detection of adrenal malignancy in participants with no prior indication for adrenal imaging, that is, masses with <= 10 HU are unlikely to be malignant. All other estimates of test performance are based on too small numbers. Conclusions: Despite their widespread use in routine assessment, there is insufficient evidence for the diagnostic value of individual imaging tests in distinguishing benign from malignant adrenal masses. Future research is urgently needed and should include prospective test validation studies for imaging and novel diagnostic approaches alongside detailed health economics analysis. KW - Positron-emission-tomography KW - Cell lung canger KW - Adrenocortial carcinomas KW - Disease prevalence KW - Spin echo KW - Contrast-enhanced CT KW - Test accuracy KW - Methodological quality KW - F-18-FDG PET/CT KW - MR Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188086 VL - 175 IS - 2 ER - TY - JOUR A1 - Floss, Doreen M. A1 - Klöcker, Tobias A1 - Schröder, Jutta A1 - Lamertz, Larissa A1 - Mrotzek, Simone A1 - Strobl, Birgit A1 - Hermanns, Heike A1 - Scheller, Jürgen T1 - Defining the functional binding sites of interleukin 12 receptor beta 1 and interleukin 23 receptor to Janus kinases JF - Molecular Biology of the Cell N2 - The interleukin (IL)-12-type cytokines IL-12 and IL-23 are involved in T-helper (Th) 1 and Th17 immunity, respectively. They share the IL-12 receptor beta 1 (IL-12R beta 1) as one component of their receptor signaling complexes, with IL-12R beta 2 as second receptor for IL-12 and IL-23R for IL-23 signal transduction. Stimulation with IL-12 and IL-23 results in activation of receptor-associated Janus kinases (Jak) and phosphorylation of STAT proteins in target cells. The Janus kinase tyrosine kinase (Tyk) 2 associates with IL-12R beta 1, whereas Jak2 binds to IL-23R and also to IL-12R beta 2. Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within the intracellular domain of the receptor chains. Here we define the Box1 and Box2 motifs in IL-12R beta 1 and an unusual Jak2-binding site in IL-23R by the use of deletion and site-directed mutagenesis. Our data show that nonfunctional box motifs abolish IL-12- and IL-23-induced STAT3 phosphorylation and cytokine-dependent proliferation of Ba/F3 cells. Coimmunoprecipitation of Tyk2 by IL-12R beta 1 and Jak2 by IL-23R supported these findings. In addition, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 signaling, whereas Tyk2 seems to be dispensable. KW - Tyrosine phosphorylation KW - Cytokine receptors KW - Intracellular domain KW - IL-12 family KW - Responses KW - Signal transduction KW - T-cells KW - STAT3 activation KW - Jak kinases KW - Inflammation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188104 VL - 27 IS - 14 ER - TY - JOUR A1 - Nitsche, Wolfgang H. A1 - Kim, Na Young A1 - Roumpos, Georgios A1 - Schneider, Christian A1 - Höfling, Sven A1 - Forchel, Alfred A1 - Yamamoto, Yoshihisa T1 - Spatial correlation of two-dimensional bosonic multimode condensates JF - Physical Review A N2 - The Berezinskii-Kosterlitz-Thouless (BKT) theorem predicts that two-dimensional bosonic condensates exhibit quasi-long-range order which is characterized by a slow decay of the spatial coherence. However previous measurements on exciton-polariton condensates revealed that their spatial coherence can decay faster than allowed under the BKT theory, and different theoretical explanations have already been proposed. Through theoretical and experimental study of exciton-polariton condensates, we show that the fast decay of the coherence can be explained through the simultaneous presence of multiple modes in the condensate. KW - Exciton-polariton condensate KW - Long-range order KW - Microcavity KW - Vortices KW - Systems Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188897 VL - 93 IS - 5 ER - TY - JOUR A1 - Adrián-Martínez, S. A1 - Albert, A. A1 - André, M. A1 - Anton, G. A1 - Ardid, M. A1 - Aubert, J.-J. A1 - Avgitas, T. A1 - Baret, B. A1 - Barrios-Martí, J. A1 - Basa, S. A1 - Bertin, V. A1 - Biagi, S. A1 - Bormuth, R. A1 - Bou-Cabo, M. A1 - Bouwhuis, M.C. A1 - Bruijn, R. A1 - Brunner, J. A1 - Busto, J. A1 - Capone, A. A1 - Caramete, L. A1 - Carr, J. A1 - Celli, S. A1 - Chiarusi, T. A1 - Circella, M. A1 - Coleiro, A. A1 - Coniglione, R. A1 - Costantini, H. A1 - Coyle, P. A1 - Creusot, A. A1 - Deschamps, A. A1 - De Bonis, G. A1 - Distefano, C. A1 - Donzaud, C. A1 - Dornic, D. A1 - Drouhin, D. A1 - Eberl, T. A1 - El Bojaddaini, I. A1 - Elsässer, D. A1 - Enzenhöfer, A. A1 - Fehn, K. A1 - Felis, I. A1 - Fusco, L.A. A1 - Galatà, S. A1 - Gay, P. A1 - Geißelsöder, S. A1 - Geyer, K. A1 - Giordano, V. A1 - Gleixner, A. A1 - Glotin, H. A1 - Gracia-Ruiz, R. A1 - Graf, K. A1 - Hallmann, S. A1 - van Haren, H. A1 - Heijboer, A.J. A1 - Hello, Y. A1 - Hernández-Rey, J.-J. A1 - Hößl, J. A1 - Hofestädt, J. A1 - Hugon, C. A1 - Illuminati, G. A1 - James, C.W. A1 - de Jong, M. A1 - Kadler, M. A1 - Kalekin, O. A1 - Katz, U. A1 - Kießling, D. A1 - Kouchner, A. A1 - Kreter, M. A1 - Kreykenbohm, I. A1 - Kulikovskiy, V. A1 - Lachaud, C. A1 - Lahmann, R. A1 - Lefèvre, D. A1 - Leonora, E. A1 - Loucatos, S. A1 - Marcelin, M. A1 - Margiotta, A. A1 - Marinelli, A. A1 - Martínez-Mora, J.A. A1 - Mathieu, A. A1 - Michael, T. A1 - Migliozzi, P. A1 - Moussa, A. A1 - Mueller, C. A1 - Nezri, E. A1 - Păvălaș, G.E. A1 - Pellegrino, C. A1 - Perrina, C. A1 - Piattelli, P. A1 - Popa, V. A1 - Pradier, T. A1 - Racca, C. A1 - Riccobene, G. A1 - Roensch, K. A1 - Saldaña, M. A1 - Samtleben, D.F.E. A1 - Sanguineti, M. A1 - Sapienza, P. A1 - Schnabel, J. A1 - Schüssler, F. A1 - Seitz, T. A1 - Sieger, C. A1 - Spurio, M. A1 - Stolarczyk, Th. A1 - Sánchez-Losa, A. A1 - Taiuti, M. A1 - Trovato, A. A1 - Tselengidou, M. A1 - Turpin, D. A1 - Tönnis, C. A1 - Vallage, B. A1 - Vallée, C. A1 - Van Elewyck, V. A1 - Vivolo, D. A1 - Wagner, S. A1 - Wilms, J. A1 - Zornoza, J.D. A1 - Zúñiga, J. T1 - A search for Secluded Dark Matter in the Sun with the ANTARES neutrino telescope JF - Journal of Cosmology and Astroparticle Physics N2 - A search for Secluded Dark Matter annihilation in the Sun using 2007-2012 data of the ANTARES neutrino telescope is presented. Three different cases are considered: a) detection of dimuons that result from the decay of the mediator, or neutrino detection from: b) mediator that decays into a dimuon and, in turn, into neutrinos, and c) mediator that decays directly into neutrinos. As no significant excess over background is observed, constraints are derived on the dark matter mass and the lifetime of the mediator. KW - dark matter experiments KW - neutrino detectors KW - dark matter detectors KW - neutrino astronomy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189035 VL - 2016 IS - 5 ER - TY - JOUR A1 - Boll, Sabine A1 - Bartholomaeus, Marie A1 - Peter, Ulrike A1 - Lupke, Ulrike A1 - Gamer, Matthias T1 - Attentional mechanisms of social perception are biased in social phobia JF - Journal of Anxiety Disorders N2 - Previous studies of social phobia have reported an increased vigilance to social threat cues but also an avoidance of socially relevant stimuli such as eye gaze. The primary aim of this study was to examine attentional mechanisms relevant for perceiving social cues by means of abnormalities in scanning of facial features in patients with social phobia. In two novel experimental paradigms, patients with social phobia and healthy controls matched on age, gender and education were compared regarding their gazing behavior towards facial cues. The first experiment was an emotion classification paradigm which allowed for differentiating reflexive attentional shifts from sustained attention towards diagnostically relevant facial features. In the second experiment, attentional orienting by gaze direction was assessed in a gaze-cueing paradigm in which non-predictive gaze cues shifted attention towards or away from subsequently presented targets. We found that patients as compared to controls reflexively oriented their attention more frequently towards the eyes of emotional faces in the emotion classification paradigm. This initial hypervigilance for the eye region was observed at very early attentional stages when faces were presented for 150 ms, and persisted when facial stimuli were shown for 3 s. Moreover, a delayed attentional orienting into the direction of eye gaze was observed in individuals with social phobia suggesting a differential time course of eye gaze processing in patients and controls. Our findings suggest that basic mechanisms of early attentional exploration of social cues are biased in social phobia and might contribute to the development and maintenance of the disorder. KW - Social anxiety KW - Eye gaze KW - Vigilance KW - Amygdala KW - Emotional expression KW - Gaze perception Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189046 VL - 40 ER - TY - JOUR A1 - Wheeler, Nicole E. A1 - Barquist, Lars A1 - Kingsley, Robert A. A1 - Gardner, Paul P. T1 - A profile-based method for identifying functional divergence of orthologous genes in bacterial genomes JF - Bioinformatics N2 - Motivation: Next generation sequencing technologies have provided us with a wealth of information on genetic variation, but predi cting the functional significance of this variation is a difficult task. While many comparative genomics studies have focused on gene flux and large scale changes, relatively little attention has been paid to quantifying the effects of single nucleotide polymorphisms and indels on protein function, particularly in bacterial genomics. Results: We present a hidden Markov model based approach we call delta-bitscore (DBS) for identifying orthologous proteins that have diverged at the amino acid sequence level in a way that is likely to impact biological function. We benchmark this approach with several widely used datasets and apply it to a proof-of-concept study of orthologous proteomes in an investigation of host adaptation in Salmonella enterica. We highlight the value of the method in identifying functional divergence of genes, and suggest that this tool may be a better approach than the commonly used dN/dS metric for identifying functionally significant genetic changes occurring in recently diverged organisms. KW - Host adaptation KW - Salmonella-enteritidis KW - Sequence identity KW - Rapid evolution KW - Variants KW - Cystic-fibriosis KW - Strains KW - Pathogenicity KW - Typhimurium KW - Yersinia Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186502 VL - 32 IS - 23 ER - TY - JOUR A1 - Plauth, Annabell A1 - Geikowski, Anne A1 - Cichon, Susanne A1 - Wowro, Sylvia J. A1 - Liedgens, Linda A1 - Rousseau, Morten A1 - Weidner, Christopher A1 - Fuhr, Luise A1 - Kliem, Magdalena A1 - Jenkins, Gail A1 - Lotito, Silvina A1 - Wainwright, Linda J. A1 - Sauer, Sascha T1 - Hormetic shifting of redox environment by pro-oxidative resveratrol protects cells against stress JF - Free Radical Biology and Medicine N2 - Resveratrol has gained tremendous interest owing to multiple reported health-beneficial effects. However, the underlying key mechanism of action of this natural product remained largely controversial. Here, we demonstrate that under physiologically relevant conditions major biological effects of resveratrol can be attributed to its generation of oxidation products such as reactive oxygen species (ROS). At low nontoxic concentrations (in general < 50 mu M), treatment with resveratrol increased viability in a set of representative cell models, whereas application of quenchers of ROS completely truncated these beneficial effects. Notably, resveratrol treatment led to mild, Nrf2-specific gene expression reprogramming. For example, in primary epidermal keratinocytes derived from human skin this coordinated process resulted in a 1.3-fold increase of endogenously generated glutathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61 mV mmol GSH per g protein. After induction of oxidative stress by using 0.78% (v/v) ethanol, endogenous generation of ROS was consequently reduced by 24% in resveratrol pre-treated cells. In contrast to the common perception that resveratrol acts mainly as a chemical antioxidant or as a target protein-specific ligand, we propose that the cellular response to resveratrol treatment is essentially based on oxidative triggering. In physiological microenvironments this molecular training can lead to hormetic shifting of cellular defense towards a more reductive state to improve physiological resilience to oxidative stress. KW - Trans-reservatrol KW - Hydrogen-peroxide KW - In-vitro KW - Hormesis KW - Ethanol KW - Oxygen KW - Nrf2 KW - Glutathione KW - Metabolism KW - Polyphenols KW - ROS KW - Oxidative stress KW - Redox environment KW - Skin KW - Epidermis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187186 VL - 99 ER - TY - JOUR A1 - Sterkenburg, Anthe S. A1 - Hoffmann, Anika A1 - Reichel, Julia A1 - Lohle, Kristin A1 - Eveslage, Maria A1 - Warmuth-Metz, Monika A1 - Müller, Hermann L. T1 - Nuchal skinfold thickness: A novel parameter for assessment of body composition in childhood craniopharyngioma JF - Journal of Clinical Endocrinology & Metabolism N2 - Context: Hypothalamic obesity, cardiovascular disease (CVD), and relapse/progression have a major impact on prognosis in childhood-onset craniopharyngioma (CP). We analyzed nuchal skinfold thickness (NST) on magnetic resonance imaging performed for follow-up monitoring as a novel parameter for body composition (BC) and CVD in CP. Objective: The objective of the study was to identify the association of NST with body mass index (BMI), waist to height ratio (WHtR), functional capacity, and blood pressure (BP) in CP and controls. Design: This was a cross-sectional and longitudinal prospective study in CP patients. Setting: The study was conducted at HIT-Endo, KRANIOPHARYNGEOM 2000/2007. Patients: Participants included 94 CP patients and 75 controls. Interventions: There were no interventions. Main Outcome Measures: Association of NST with BC and BP in 43 CP and 43 controls was measured. Results: NST correlated with BMI SD score (SDS; r = 0.78; P = .001; n = 169) and WHtR (r = 0.85; P = .001; n = 86) in the total cohort and CP patients (NST-BMI SDS: r = 0.77, P = .001, n = 94); NST-WHtR: r = 0.835, P = .001, n = 43) and controls (NST-BMI SDS: r = 0.792, P = .001, n = 75; NST-WHtR: r = 0.671, P = .001, n = 43). In CP, systolic BP correlated with NST (r = 0.575, P = .001), BMI SDS (r = 0.434, P = .004), and WHtR (r = 0.386, P = .011). Similar results were observed for diastolic BP in CP. In multivariate analyses, NST had a predictive value for hypertension in postpubertal CP and controls (odds ratio 6.98, 95% confidence interval 1.65, 29.5], P = .008). During a longitudinal follow-up, changes in NST correlated with changes in BMI SDS (P = .001) and WHtR (P = .01) but not with changes in BP and functional capacity. Conclusions: Because monitoring of magnetic resonance imaging and BC is essential for follow-up in CP, NST could serve as a novel and clinically relevant parameter for longitudinal assessment of BC and CVD risk in CP. KW - to-height ratio KW - subcutaneous adipose-tissue KW - disease risk-factors KW - long-term survivors KW - guality-of-life KW - mass index KW - neck circumference KW - onset craniopharyngioma KW - german multicenter KW - visceral adiposity Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186562 VL - 101 IS - 12 ER - TY - JOUR A1 - Perkovic, Vlado A1 - Agarwal, Rajiv A1 - Fioretto, Paola A1 - Hemmelgarn, Brenda R. A1 - Levin, Adeera A1 - Thomas, Merlin C. A1 - Wanner, Christoph A1 - Kasiske, Bertram L. A1 - Wheeler, David C. A1 - Groop, Per-Henrik T1 - Management of patients with diabetes and CKD: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) controversies conference JF - Kidney International N2 - The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development. This conference was convened to assess our current state of knowledge regarding optimal glycemic control, current antidiabetic agents and their safety, and new therapies being developed to improve kidney function and cardiovascular outcomes for this vulnerable population. KW - stage renal-disease KW - converting enzyme-inhibition KW - dietary sodium restriction KW - intensive glucose control KW - albumin excretion rate KW - blood pressure KW - cardiovascular outcomes KW - randomized trial KW - glycemic control KW - receptor KW - antidiabetic agents KW - cardiovascular disease KW - chronic kidney disease KW - diabetes KW - renoprotection KW - antagonist Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186599 VL - 90 IS - 6 ER - TY - JOUR A1 - Hassouna, I. A1 - Ott, C. A1 - Wüstefeld, L. A1 - Offen, N. A1 - Neher, R. A. A1 - Mitkovski, M. A1 - Winkler, D. A1 - Sperling, S. A1 - Fries, L. A1 - Goebbels, S. A1 - Vreja, I. C. A1 - Hagemeyer, N. A1 - Dittrich, M. A1 - Rossetti, M. F. A1 - Kröhnert, K. A1 - Hannke, K. A1 - Boretius, S. A1 - Zeug, A. A1 - Höschen, C. A1 - Dandekar, T. A1 - Dere, E. A1 - Neher, E. A1 - Rizzoli, S. O. A1 - Nave, K.-A. A1 - Sirén, A.-L. A1 - Ehrenreich, H. T1 - Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus JF - Molecular Psychiatry N2 - Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of similar to 20%. Under constant cognitive challenge, neuron numbers remained elevated until >6 months of age. Surprisingly, this increase occurred in absence of altered cell proliferation or apoptosis. After feeding a \(^{15}\)N-leucine diet, we used nanoscopic secondary ion mass spectrometry, and found that in EPO-treated mice, an equivalent number of neurons was defined by elevated \(^{15}\)N-leucine incorporation. In EPO-treated NG2-Cre-ERT2 mice, we confirmed enhanced differentiation of preexisting oligodendrocyte precursors in the absence of elevated DNA synthesis. A corresponding analysis of the neuronal lineage awaits the identification of suitable neuronal markers. In cultured neurospheres, EPO reduced Sox9 and stimulated miR124, associated with advanced neuronal differentiation. We are discussing a resulting working model in which EPO drives the differentiation of non-dividing precursors in both (NG2+) oligodendroglial and neuronal lineages. As endogenous EPO expression is induced by brain injury, such a mechanism of adult neurogenesis may be relevant for central nervous system regeneration. KW - neural stem-cells KW - recombinat-human-erythropoietin KW - cognitive functions KW - pyramidal neurons KW - nervous-sytem KW - brain-injury KW - mouse-brain KW - progenitors KW - mice KW - memory Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186669 VL - 21 IS - 12 ER - TY - JOUR A1 - Schneider, Eberhard A1 - Dittrich, Marcus A1 - Böck, Julia A1 - Nanda, Indrajit A1 - Müller, Tobias A1 - Seidmann, Larissa A1 - Tralau, Tim A1 - Galetzka, Danuta A1 - El Hajj, Nady A1 - Haaf, Thomas T1 - CpG sites with continuously increasing or decreasing methylation from early to late human fetal brain development JF - Gene N2 - Normal human brain development is dependent on highly dynamic epigenetic processes for spatial and temporal gene regulation. Recent work identified wide-spread changes in DNA methylation during fetal brain development. We profiled CpG methylation in frontal cortex of 27 fetuses from gestational weeks 12-42, using Illumina 450K methylation arrays. Sites showing genome-wide significant correlation with gestational age were compared to a publicly available data set from gestational weeks 3-26. Altogether, we identified 2016 matching developmentally regulated differentially methylated positions (m-dDMPs): 1767 m-dDMPs were hypermethylated and 1149 hypomethylated during fetal development. M-dDMPs are underrepresented in CpG islands and gene promoters, and enriched in gene bodies. They appear to cluster in certain chromosome regions. M-dDMPs are significantly enriched in autism-associated genes and CpGs. Our results promote the idea that reduced methylation dynamics during fetal brain development may predispose to autism. In addition, m-dDMPs are enriched in genes with human-specific brain expression patterns and/or histone modifications. Collectively, we defined a subset of dDMPs exhibiting constant methylation changes from early to late pregnancy. The same epigenetic mechanisms involving methylation changes in cis-regulatory regions may have been adopted for human brain evolution and ontogeny. KW - Autism spectrum disorders KW - DNA methylation KW - Genome KW - Autism KW - Frontal cortex KW - Human prefrontal cortex KW - Gene-expression KW - Schizophrenia KW - Patterns KW - Transcription KW - Epigenetics KW - Environment KW - Fetal brain development KW - DNA methylation dynamics KW - Methylome Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186936 VL - 592 IS - 1 ER - TY - JOUR A1 - Laiho, K. A1 - Pressl, B. A1 - Schlager, A. A1 - Suchomel, H. A1 - Kamp, M. A1 - Höfling, S. A1 - Schneider, C. A1 - Weihs, G. T1 - Uncovering dispersion properties in semiconductor waveguides to study photon-pair generation JF - Nanotechnology N2 - We investigate the dispersion properties of ridge Bragg-reflection waveguides to deduce their phasematching characteristics. These are crucial for exploiting them as sources of parametric down-conversion (PDC). In order to estimate the phasematching bandwidth we first determine the group refractive indices of the interacting modes via Fabry-Perot experiments in two distant wavelength regions. Second, by measuring the spectra of the emitted PDC photons, we gain access to their group index dispersion. Our results offer a simple approach for determining the PDC process parameters in the spectral domain, and provide important feedback for designing such sources, especially in the broadband case. KW - Parametric down-conversion KW - Entanglement KW - CHIP KW - PUMP KW - Bragg-reflection waveguide KW - Information KW - phasematching KW - group refractive index Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187025 VL - 27 IS - 43 ER - TY - JOUR A1 - Regn, Michael A1 - Laggerbauer, Bernhard A1 - Jentzsch, Claudia A1 - Ramanujam, Deepak A1 - Ahles, Andrea A1 - Sichler, Sonja A1 - Calzada-Wack, Julia A1 - Koenen, Rory R. A1 - Braun, Attila A1 - Nieswandt, Bernhard A1 - Engelhardt, Stefan T1 - Peptidase inhibitor 16 is a membrane-tethered regulator of chemerin processing in the myocardium JF - Journal of Molecular and Cellular Cardiology N2 - A key response of the myocardium to stress is the secretion of factors with paracrine or endocrine function. Intriguing in this respect is peptidase inhibitor 16 (PI16), a member of the CAP family of proteins which we found to be highly upregulated in cardiac disease. Up to this point, the mechanism of action and physiological function of PI16 remained elusive. Here, we show that PI16 is predominantly expressed by cardiac fibroblasts, which expose PI16 to the interstitium via a glycophosphatidylinositol (-GPI) membrane anchor. Based on a reported genetic association of PI16 and plasma levels of the chemokine chemerin, we investigated whether PI16 regulates post-translational processing of its precursor pro-chemerin. PI16-deficient mice were engineered and found to generate higher levels of processed chemerin than wildtype mice. Purified recombinant PI16 efficiently inhibited cathepsin K, a chemerin-activating protease, in vitro. Moreover, we show that conditioned medium from PI16-overexpressing cells impaired the activation of pro-chemerin. Together, our data indicate that PI16 suppresses chemerin activation in the myocardium and suggest that this circuit may be part of the cardiac stress response. KW - Cells KW - Activation KW - Purification KW - Protein KW - Peptidase inhibitor 16 (PI16) KW - Identification KW - Inflammation KW - Adipokine KW - Metabolism KW - Heart KW - Mice KW - Chemerin KW - RARRES2 KW - TIG2 KW - Protease inhibition KW - Chemerin processing Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187039 VL - 99 ER - TY - JOUR A1 - Chopra, Martin A1 - Biehl, Marlene A1 - Steinfatt, Tim A1 - Brandl, Andreas A1 - Kums, Juliane A1 - Amich, Jorge A1 - Vaeth, Martin A1 - Kuen, Janina A1 - Holtappels, Rafaela A1 - Podlech, Jürgen A1 - Mottok, Anja A1 - Kraus, Sabrina A1 - Jordán-Garotte, Ana-Laura A1 - Bäuerlein, Carina A. A1 - Brede, Christian A1 - Ribechini, Eliana A1 - Fick, Andrea A1 - Seher, Axel A1 - Polz, Johannes A1 - Ottmueller, Katja J. A1 - Baker, Jeannette A1 - Nishikii, Hidekazu A1 - Ritz, Miriam A1 - Mattenheimer, Katharina A1 - Schwinn, Stefanie A1 - Winter, Thorsten A1 - Schäfer, Viktoria A1 - Krappmann, Sven A1 - Einsele, Hermann A1 - Müller, Thomas D. A1 - Reddehase, Matthias J. A1 - Lutz, Manfred B. A1 - Männel, Daniela N. A1 - Berberich-Siebelt, Friederike A1 - Wajant, Harald A1 - Beilhack, Andreas T1 - Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion JF - Journal of Experimental Medicine N2 - Donor CD4\(^+\)Foxp3\(^+\) regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology. Expanding radiation-resistant host T reg cells in recipient mice using a mouse TNFR2-selective agonist before allo-HCT significantly prolonged survival and reduced GvHD severity in a TNFR2-and T reg cell-dependent manner. The beneficial effects of transplanted T cells against leukemia cells and infectious pathogens remained unaffected. A corresponding human TNFR2-specific agonist expanded human T reg cells in vitro. These observations indicate the potential of our strategy to protect allo-HCT patients from acute GvHD by expanding T reg cells via selective TNFR2 activation in vivo. KW - Tumor-necrosis-factor KW - Regulatory-cells KW - Bone marrow transplantantation KW - Graft-versus-leukemia KW - Rheumatoid arthritis KW - Autoimmune diseases KW - Factor receptor KW - Alpha therapy KW - Expression KW - Suppression Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187640 VL - 213 IS - 9 ER - TY - JOUR A1 - Schmitt, Dominique A1 - Funk, Natalia A1 - Blum, Robert A1 - Asan, Esther A1 - Andersen, Lill A1 - Rülicke, Thomas A1 - Sendtner, Michael A1 - Buchner, Erich T1 - Initial characterization of a Syap1 knock-out mouse and distribution of Syap1 in mouse brain and cultured motoneurons JF - Histochemistry and Cell Biology N2 - Synapse-associated protein 1 (Syap1/BSTA) is the mammalian homologue of Sap47 (synapse-associated protein of 47 kDa) in Drosophila. Sap47 null mutant larvae show reduced short-term synaptic plasticity and a defect in associative behavioral plasticity. In cultured adipocytes, Syap1 functions as part of a complex that phosphorylates protein kinase B alpha/Akt1 (Akt1) at Ser\(^{473}\) and promotes differentiation. The role of Syap1 in the vertebrate nervous system is unknown. Here, we generated a Syap1 knock-out mouse and show that lack of Syap1 is compatible with viability and fertility. Adult knock-out mice show no overt defects in brain morphology. In wild-type brain, Syap1 is found widely distributed in synaptic neuropil, notably in regions rich in glutamatergic synapses, but also in perinuclear structures associated with the Golgi apparatus of specific groups of neuronal cell bodies. In cultured motoneurons, Syap1 is located in axons and growth cones and is enriched in a perinuclear region partially overlapping with Golgi markers. We studied in detail the influence of Syap1 knockdown and knockout on structure and development of these cells. Importantly, Syap1 knockout does not affect motoneuron survival or axon growth. Unexpectedly, neither knockdown nor knockout of Syap1 in cultured motoneurons is associated with reduced Ser\(^{473}\) or Thr\(^{308}\) phosphorylation of Akt. Our findings demonstrate a widespread expression of Syap1 in the mouse central nervous system with regionally specific distribution patterns as illustrated in particular for olfactory bulb, hippocampus, and cerebellum. KW - Protein kinase B KW - Spinal Muscular-arthropy KW - Rictor-mTOR complex KW - Neurotrophic factors KW - Plasma-membrane KW - Axon growth KW - SAP47 gene KW - Phosphorylation KW - Drosophilia KW - Cells KW - BSTA KW - Viability KW - Brain KW - Syap1 localization KW - Glutamatergic synapses KW - PKB/Akt phosphorylation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187258 VL - 146 IS - 4 ER - TY - JOUR A1 - Markert, Sebastian Matthias A1 - Britz, Sebastian A1 - Proppert, Sven A1 - Lang, Marietta A1 - Witvliet, Daniel A1 - Mulcahy, Ben A1 - Sauer, Markus A1 - Zhen, Mei A1 - Bessereau, Jean-Louis A1 - Stigloher, Christian T1 - Filling the gap: adding super-resolution to array tomography for correlated ultrastructural and molecular identification of electrical synapses at the C. elegans connectome JF - Neurophotonics N2 - Correlating molecular labeling at the ultrastructural level with high confidence remains challenging. Array tomography (AT) allows for a combination of fluorescence and electron microscopy (EM) to visualize subcellular protein localization on serial EM sections. Here, we describe an application for AT that combines near-native tissue preservation via high-pressure freezing and freeze substitution with super-resolution light microscopy and high-resolution scanning electron microscopy (SEM) analysis on the same section. We established protocols that combine SEM with structured illumination microscopy (SIM) and direct stochastic optical reconstruction microscopy (dSTORM). We devised a method for easy, precise, and unbiased correlation of EM images and super-resolution imaging data using endogenous cellular landmarks and freely available image processing software. We demonstrate that these methods allow us to identify and label gap junctions in Caenorhabditis elegans with precision and confidence, and imaging of even smaller structures is feasible. With the emergence of connectomics, these methods will allow us to fill in the gap-acquiring the correlated ultrastructural and molecular identity of electrical synapses. KW - caenorhabditis elegans KW - localization micoscopy KW - fluorescent-probes KW - junction proteins KW - resolution limit KW - direct stochasticoptical reconstruction microscopy KW - structured illumination microscopy KW - correlative light and electron microscopy KW - gap junction KW - neural circuits KW - nervous-system KW - image data KW - reconstruction KW - innexins KW - super-resolution microscopy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187292 VL - 3 IS - 4 ER - TY - JOUR A1 - Groeber, Florian A1 - Schober, Lena A1 - Schmid, Freia F. A1 - Traube, Andrea A1 - Kolbus-Hernandez, Silvia A1 - Daton, Karolina A1 - Hoffmann, Sebastian A1 - Petersohn, Dirk A1 - Schaefer-Korting, Monika A1 - Walles, Heike A1 - Mewes, Karsten R. T1 - Catch-up validation study of an in vitro skin irritation test method based on an open source reconstructed epidermis (phase II) JF - Toxicology in Vitro N2 - To replace the Draize skin irritation assay (OECD guideline 404) several test methods based on reconstructed human epidermis (RHE) have been developed and were adopted in the OECD test guideline 439. However, all validated test methods in the guideline are linked to RHE provided by only three companies. Thus,the availability of these test models is dependent on the commercial interest of the producer. To overcome this limitation and thus to increase the accessibility of in vitro skin irritation testing, an open source reconstructed epidermis (OS-REp) was introduced. To demonstrate the capacity of the OS-REp in regulatory risk assessment, a catch-up-validation study was performed. The participating laboratories used in-house generated OS-REp to assess the set of 20 reference substances according to the performance standards amending the OECD test guideline 439. Testing was performed under blinded conditions. The within-laboratory reproducibility of 87% and the inter-laboratory reproducibility of 85% prove a high reliability of irritancy testing using the OS-REp protocol. In addition, the prediction capacity was with an accuracy of 80% comparable to previous published RHE based test protocols. Taken together the results indicate that the OS-REp test method can be used as a standalone alternative skin irritation test replacing the OECD test guideline 404. KW - Model KW - Chemicals KW - Assay KW - Episkin KW - Vivo KW - RHE KW - In vitro skin irritation testing KW - Open source reconstructed epidermis KW - Validation KW - Alternative test methods Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187311 VL - 36 ER - TY - JOUR A1 - Chumak, Tetyana A1 - Rüttiger, Lukas A1 - Lee, Sze Chim A1 - Campanelli, Dario A1 - Zuccotti, Annalisa A1 - Singer, Wibke A1 - Popelář, Jiří A1 - Gutsche, Katja A1 - Geisler, Hyun-Soon A1 - Schraven, Sebastian Philipp A1 - Jaumann, Mirko A1 - Panford-Walsh, Rama A1 - Hu, Jing A1 - Schimmang, Thomas A1 - Zimmermann, Ulrike A1 - Syka, Josef A1 - Knipper, Marlies T1 - BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury JF - Molecular Neurobiology N2 - For all sensory organs, the establishment of spatial and temporal cortical resolution is assumed to be initiated by the first sensory experience and a BDNF-dependent increase in intracortical inhibition. To address the potential of cortical BDNF for sound processing, we used mice with a conditional deletion of BDNF in which Cre expression was under the control of the Pax2 or TrkC promoter. BDNF deletion profiles between these mice differ in the organ of Corti (BDNF \(^{Pax2}\) -KO) versus the auditory cortex and hippocampus (BDNF \(^{TrkC}\) -KO). We demonstrate that BDNF \(^{Pax2}\) -KO but not BDNF \(^{TrkC}\) -KO mice exhibit reduced sound-evoked suprathreshold ABR waves at the level of the auditory nerve (wave I) and inferior colliculus (IC) (wave IV), indicating that BDNF in lower brain regions but not in the auditory cortex improves sound sensitivity during hearing onset. Extracellular recording of IC neurons of BDNF \(^{Pax2}\) mutant mice revealed that the reduced sensitivity of auditory fibers in these mice went hand in hand with elevated thresholds, reduced dynamic range, prolonged latency, and increased inhibitory strength in IC neurons. Reduced parvalbumin-positive contacts were found in the ascending auditory circuit, including the auditory cortex and hippocampus of BDNF \(^{Pax2}\) -KO, but not of BDNF \(^{TrkC}\) -KO mice. Also, BDNF \(^{Pax2}\) -WT but not BDNF \(^{Pax2}\) -KO mice did lose basal inhibitory strength in IC neurons after acoustic trauma. These findings suggest that BDNF in the lower parts of the auditory system drives auditory fidelity along the entire ascending pathway up to the cortex by increasing inhibitory strength in behaviorally relevant frequency regions. Fidelity and inhibitory strength can be lost following auditory nerve injury leading to diminished sensory outcome and increased central noise. KW - Inner hair cell KW - Neurotropathic Factor KW - Hearing-loss KW - Alzheimers-disease KW - low-threshold fibers KW - cochlear nucleus neurons KW - Frequency-response areas KW - Inferior colliculus KW - Environmental enrichment KW - Synaptic plasticity KW - Cortical plasticity KW - BDNF KW - Central hyperactivity KW - High-spontaneous rate KW - Homeostatic plasticity KW - Sound detection threshold Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187341 VL - 53 IS - 8 ER - TY - JOUR A1 - Wieser, Matthias J. A1 - Reicherts, Philipp A1 - Juravle, Georgiana A1 - von Leupoldt, Andreas T1 - Attention mechanisms during predictable and unpredictable threat - a steady-state visual evoked potential approach JF - NeuroImage N2 - Fear is elicited by imminent threat and leads to phasic fear responses with selective attention, whereas anxiety is characterized by a sustained state of heightened vigilance due to uncertain danger. In the present study, we investigated attention mechanisms in fear and anxiety by adapting the NPU-threat test to measure steady-state visual evoked potentials (ssVEPs). We investigated ssVEPs across no aversive events (N), predictable aversive events (P), and unpredictable aversive events (U), signaled by four-object arrays (30 s). In addition, central cues were presented during all conditions but predictably signaled imminent threat only during the P condition. Importantly, cues and context events were flickered at different frequencies (15 Hz vs. 20 Hz) in order to disentangle respective electrocortical responses. The onset of the context elicited larger electrocortical responses for U compared to P context. Conversely, P cues elicited larger electrocortical responses compared to N cues. Interestingly, during the presence of the P cue, visuocortical processing of the concurrent context was also enhanced. The results support the notion of enhanced initial hypervigilance to unpredictable compared to predictable threat contexts, while predictable cues show electrocortical enhancement of the cues themselves but additionally a boost of context processing. KW - Event-related potential KW - Contextual fear KW - Conditioning evidence KW - Sustained attention KW - Selective attention KW - Aversive events KW - Time-course KW - Virtual-reality KW - Anxiety KW - Humans Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187365 VL - 139 ER - TY - JOUR A1 - Szczerba, Wojciech A1 - Zukrowski, Jan A1 - Przybylski, Marek A1 - Sikora, Marcin A1 - Safonova, Olga A1 - Shmeliov, Aleksey A1 - Nicolosi, Valeria A1 - Schneider, Michael A1 - Granath, Tim A1 - Oppmann, Maximilian A1 - Straßer, Marion A1 - Mandel, Karl T1 - Pushing up the magnetisation values for iron oxide nanoparticles via zinc doping: X-ray studies on the particle's sub-nano structure of different synthesis routes JF - Physical Chemistry Chemical Physics N2 - The maximum magnetisation (saturation magnetisation) obtainable for iron oxide nanoparticles can be increased by doping the nanocrystals with non-magnetic elements such as zinc. Herein, we closely study how only slightly different synthesis approaches towards such doped nanoparticles strongly influence the resulting sub-nano/atomic structure. We compare two co-precipitation approaches, where we only vary the base (NaOH versus NH\(_3\)), and a thermal decomposition route. These methods are the most commonly applied ones for synthesising doped iron oxide nanoparticles. The measurable magnetisation change upon zinc doping is about the same for all systems. However, the sub-nano structure, which we studied with Mossbauer and X-ray absorption near edge spectroscopy, differs tremendously. We found evidence that a much more complex picture has to be drawn regarding what happens upon Zn doping compared to what textbooks tell us about the mechanism. Our work demonstrates that it is crucial to study the obtained structures very precisely when "playing'' with the atomic order in iron oxide nanocrystals. KW - Ferrite KW - FE Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187390 VL - 18 IS - 36 ER - TY - JOUR A1 - Dreiner, Herbi K. A1 - Krauss, Manuel E. A1 - O'Leary, Ben A1 - Opferkuch, Toby A1 - Staub, Florian T1 - Validity of the CMSSM interpretation of the diphoton excess JF - Physical Review D N2 - It has been proposed that the observed diphoton excess at 750 GeV could be explained within the constrained minimal supersymmetric standard model via resonantly produced stop bound states. We reanalyze this scenario critically and extend previous work to include the constraints from the stability of the electroweak vacuum and from the decays of the stoponium into a pair of Higgs bosons. It is shown that the interesting regions of parameter space with a light stop and Higgs of the desired mass are ruled out by these constraints. This conclusion is not affected by the presence of the bound states because the binding energy is usually very small in the regions of parameter space which can explain the Higgs mass. Thus, this also leads to strong constraints on the diphoton production cross section which is in general too small. KW - Minimal supersymmetric model KW - 2-loop level KW - Bound-states KW - Higgs-boson KW - MSSM KW - Mass KW - Spheno KW - Sarah KW - Spectrum KW - Breaking Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187429 VL - 94 IS - 5 ER - TY - JOUR A1 - Hopp, Sarah A1 - Albert-Weissenberger, Christiane A1 - Mencl, Stine A1 - Bieber, Michael A1 - Schuhmann, Michael K. A1 - Stetter, Christian A1 - Nieswandt, Bernhard A1 - Schmidt, Peter M. A1 - Monoranu, Camelia-Maria A1 - Alafuzoff, Irina A1 - Marklund, Niklas A1 - Nolte, Marc W. A1 - Sirén, Anna-Leena A1 - Kleinschnitz, Christoph T1 - Targeting coagulation factor XII as a novel therapeutic option in brain trauma JF - Annals of Neurology N2 - Objective: Traumatic brain injury is a major global public health problem for which specific therapeutic interventions are lacking. There is, therefore, a pressing need to identify innovative pathomechanism-based effective therapies for this condition. Thrombus formation in the cerebral microcirculation has been proposed to contribute to secondary brain damage by causing pericontusional ischemia, but previous studies have failed to harness this finding for therapeutic use. The aim of this study was to obtain preclinical evidence supporting the hypothesis that targeting factor XII prevents thrombus formation and has a beneficial effect on outcome after traumatic brain injury. Methods: We investigated the impact of genetic deficiency of factor XII and acute inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused infestin-4 (rHA-Infestin-4) on trauma-induced microvascular thrombus formation and the subsequent outcome in 2 mouse models of traumatic brain injury. Results: Our study showed that both genetic deficiency of factor XII and an inhibition of activated factor XII in mice minimize trauma-induced microvascular thrombus formation and improve outcome, as reflected by better motor function, reduced brain lesion volume, and diminished neurodegeneration. Administration of human factor XII in factor XII-deficient mice fully restored injury-induced microvascular thrombus formation and brain damage. Interpretation: The robust protective effect of rHA-Infestin-4 points to a novel treatment option that can decrease ischemic injury after traumatic brain injury without increasing bleeding tendencies. KW - Molecular-weight heparin KW - Thrombus formation KW - Cerebral-ischemia KW - in-vivo KW - Intravascular coagulation KW - Hemodynamic depression KW - Head-injury KW - Rats KW - Model KW - Mice Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188800 VL - 79 IS - 6 ER -