TY - JOUR A1 - Schilbach, Karin A1 - Alkhaled, Mohammed A1 - Welker, Christian A1 - Eckert, Franziska A1 - Blank, Gregor A1 - Ziegler, Hendrik A1 - Sterk, Marco A1 - Müller, Friederike A1 - Sonntag, Katja A1 - Wieder, Thomas A1 - Braumüller, Heidi A1 - Schmitt, Julia A1 - Eyrich, Matthias A1 - Schleicher, Sabine A1 - Seitz, Christian A1 - Erbacher, Annika A1 - Pichler, Bernd J. A1 - Müller, Hartmut A1 - Tighe, Robert A1 - Lim, Annick A1 - Gillies, Stephen D. A1 - Strittmatter, Wolfgang A1 - Röcken, Martin A1 - Handgretinger, Rupert T1 - Cancer-targeted IL-12 controls human rhabdomyosarcoma by senescence induction and myogenic differentiation JF - OncoImmunology N2 - Stimulating the immune system to attack cancer is a promising approach, even for the control of advanced cancers. Several cytokines that promote interferon-γ-dominated immune responses show antitumor activity, with interleukin 12 (IL-12) being of major importance. Here, we used an antibody-IL-12 fusion protein (NHS-IL12) that binds histones of necrotic cells to treat human sarcoma in humanized mice. Following sarcoma engraftment, NHS-IL12 therapy was combined with either engineered IL-7 (FcIL-7) or IL-2 (IL-2MAB602) for continuous cytokine bioavailability. NHS-IL12 strongly induced innate and adaptive antitumor immunity when combined with IL-7 or IL-2. NHS-IL12 therapy significantly improved survival of sarcoma-bearing mice and caused long-term remissions when combined with IL-2. NHS-IL12 induced pronounced cancer cell senescence, as documented by strong expression of senescence-associated p16\(^{INK4a}\) and nuclear translocation of p-HP1γ, and permanent arrest of cancer cell proliferation. In addition, this cancer immunotherapy initiated the induction of myogenic differentiation, further promoting the hypothesis that efficient antitumor immunity includes mechanisms different from cytotoxicity for efficient cancer control in vivo. KW - TH17 cells KW - cancer-targeted IL-12 KW - differentiation KW - humanized mice KW - immunocytokine KW - immunotherapy KW - M1/M2 macrophages KW - rhabdomyosarcoma KW - TH1-induced senescence KW - tumor-infiltrating lymphocytes Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154579 VL - 4 IS - 7 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 - INPR A1 - Müller, Stefan A1 - Draeger, Simon A1 - Ma, Kiaonan A1 - Hensen, Matthias A1 - Kenneweg, Tristan A1 - Pfeiffer, Walter A1 - Brixner, Tobias T1 - Fluorescence-Detected Two-Quantum and One-Quantum-Two-Quantum 2D Electronic Spectroscopy T2 - Journal of Physical Chemistry Letters N2 - We demonstrate two-quantum (2Q) coherent two-dimensional (2D)electronic spectroscopy using a shot-to-shot-modulated pulse shaper and fluorescence detection. Broadband collinear excitation is realized with the supercontinuum output of an argon-filled hollow-core fiber, enabling us to excite multiple transitions simultaneously in the visible range. The 2Q contribution is extracted via a three-pulse sequence with 16-fold phase cycling and simulated employing cresyl violet as a model system. Furthermore, we report the first experimental realization of one-quantum−two-quantum (1Q-2Q) 2D spectroscopy, offering less congested spectra as compared with the 2Q implementation. We avoid scattering artifacts and nonresonant solvent contributions by using fluorescence as the observable. This allows us to extract quantitative information about doubly excited states that agree with literature expectations. The high sensitivity and background-free nature of fluorescence detection allow for a general applicability of this method to many other systems. KW - Zweidimensionale Spektroskopie KW - elektronisch angeregte Zustände KW - Doppelquantenkohärenz KW - Fluoreszenz KW - Optische Spektroskopie KW - Molekülzustand Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173468 UR - https://pubs.acs.org/doi/10.1021/acs.jpclett.8b00541 ER - TY - CHAP A1 - Schwaneck, Stefan A1 - Glos, Michael A1 - Bofinger, Peter A1 - Straubhaar, Thomas A1 - Haase, Axel A1 - Pinkwart, Andreas A1 - Kunze, Mario A1 - Österle, Irene A1 - Seubert, Marc A1 - Nowak, Matthias A1 - Rosen, Holga A1 - Steinle, Andreas A1 - Schorr, Leander A1 - Fichtner, Caroline A1 - Fischl, Bernd A1 - Wittrock, Max A1 - Günther, Niclas A1 - Roth, Isabelle A1 - Verburg, Erik A1 - Sextl, Gerhard A1 - Heitmüller, Lars A1 - Müller, Norman A1 - Frashek, André A1 - Stetter, Ulrich T1 - Innovationen – Performancetreiber und nachhaltiger Wirtschaftsmotor in Deutschland? Festschrift zum 5. Würzburger Wirtschaftssymposium N2 - 5. Würzburger Wirtschaftssymposium, 20.11.2008 Deutsche Erfindungen verändern die Welt - heute wie vor 500 Jahren. Von Buchdruck, über Dieselmotor, Glühbirne bis hin zu Airbag, Aspirin, Dübel, Fernseher und mp3-Format. Alleine dieser bescheidene Überblick des Phänomens “Made in Germany” lässt den Betrachter die Bedeutung und das Potenzial von Innovationen am Standort Deutschland schnell erkennen. Experten aus Wirtschaft, Politik und Gesellschaft setzten sich am 20.11.2008 unter der Leitfrage: “Innovationen – Performancetreiber und nachhaltiger Wirtschaftsmotor in Deutschland?” mit der Bedeutung von Innovationen für den Standort Deutschland auseinander. Die Festschrift rundet - neben Interviews mit und Gastbeiträgen von Referenten der Veranstaltung - das 5. Würzburger Wirtschaftssymposium mit Stellungnahmen und Beiträgen renommierter Experten ab. Zu Wort kommen dabei Jungunternehmer ebenso wie Wissenschaftler der Universität Würzburg und Vertreter externer Organisationen. KW - Innovationsforschung KW - Innovationsmanagement KW - Innovationspotenzial KW - Sozialinnovation KW - Produktinnovation KW - Technische Innovation KW - Würzburg KW - Wirtschaft KW - Partner für Innovation KW - Entrepreneurship KW - Universität KW - economics KW - innovation KW - entrepreneurship Y1 - 2008 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-53559 SN - 978-3-923959-58-7 ER - TY - THES A1 - Müller, Matthias T1 - Dreidimensionale Konfigurationen von NMR Phased-Array Spulen mit vielen Einzelelementen T1 - Three-dimensional configurations of NMR phased-arrays with many coil elements N2 - In der vorliegenden Arbeit wurden alternative Phased-Array Konfigurationen untersucht, die eine gleichmäßige rÄaumliche Verteilung der Spulensensitivitäten für eine 2D parallel beschleunigte NMR-Bildgebung zur Verfügung stellen sowie eine höhere lokale Dichte probenrauschdominierter Einzelspulen als konventionelle Arraygeometrien ermöglichen. Hierzu wurde zunächst eine neuartige 16-Kanal Doppel-Spiral Arraygeometrie einem Birdcage-ähnlichen Spulenarray mit zwei Ringen aus je acht Spulenelementen gegenübergestellt, welches gewöhnlich in der klinischen Routine für NMR-Untersuchungen am menschlichen Kopf eingesetzt wird. Unter Verwendung analytischer Biot-Savart Berechnungen in der Entwicklungsumgebung Matlab konnten die jeweiligen Kodiereigenschaften sowie das mit den unterschiedlichen Arraykonfigurationen erzielbare intrinsische Signal-Rausch-Verhältnis ermittelt und verglichen werden. Zudem wurde auf gleiche Weise der Einfluss geometrischer Variationen im Aufbau des Doppel-Spiral Volumenarrays auf die intrinsische Isolation zwischen dem inneren, um +pi verdrehten und dem Äußeren, um -pi verdrehten Einfach-Spiral Spulenarray untersucht und Phased-Array Designs mit 32 unabhÄangigen Empfangselementen evaluiert. Im Rahmen einer experimentellen Evaluierung des Doppel-Spiral Arraykonzepts wurden zuerst einzelne Spulenelemente der unterschiedlichen 16-Kanal Volumenarrays verglichen, bevor eine Doppel-Spiral Phased-Array Prototypenspule aufgebaut wurde. Mit dieser konnten sowohl die vorausgesetzte intrinsische Entkopplung der zwei Einzel-Spiral Spulenarrays als auch die in alle drei Raumrichtungen homogene Verteilung der einzelnen Spulensensitivitäten anhand von Experimenten im NMR-System nachgewiesen werden. So war trotz der relativ geringen Anzahl von sechs unabhängigen Einzelkanälen eine um den Faktor 4 beschleunigte NMR-Untersuchung des menschlichen Kopfes mittels einer 3D MP-RAGE-Bildgebungssequenz möglich. Diese hohe Beschleunigung konnte für jede beliebige Orientierung der Kodierrichtungen in gleichermaßen guter Bildqualität erzielt werden und erwies sich somit als unabhängig von der gewünschten Positionierung des dreidimensionalen Untersuchungsvolumens. Das auf diese Weise bestätigte Konzept einer Doppel-Spiral Arraygeometrie stellt allerdings nicht nur eine gleichmäßige Sensitivitätsvariation entlang aller Raumrichtungen zur Verfügung, sondern ermöglicht auch eine höhere Dichte probenrauschdominierter Einzelspulen. In einem zweiten Ansatz wurde das Konzept räumlich kompakter Quadratur-Arrayelemente untersucht, die aus einer geeigneten geometrischen Kombination zweier Einzelspulen entstehen. Die Evaluierung der Leistungsfähigkeit einer derartigen Arrayelementkonfiguration erfolgte in diesem Fall durch den Vergleich einer aus vier Quadratur-Arrayelementen aufgebauten 8-Kanal Phased-Array Spule mit einem konventionellen 4-Kanal Spulenarray, welches sich aus vier waagrechten, in Reihen angeordneten Einzelspulen zusammensetzt. Die Kodiereigenschaften der jeweiligen Phased-Array Spulen sowie das zur Verfügung stehende intrinsische SNR wurden erneut mit Hilfe von Biot-Savart Simulationen in Matlab ermittelt. Diese zeigten, dass durch eine solche neuartige Elementkonfiguration eine Steigerung des erzielbaren Signal-Rausch-Verhältnisses von nahezu 30% erreicht werden kann. Zudem konnte eine deutliche Verbesserung der Kodiereigenschaften in Folge einer, bei gleicher Ausdehnung der Arraystruktur, verdoppelten Anzahl an Einzelspulen beobachtet werden. Eine experimentelle Untersuchung erfolgte anhand einer einfachen aus vier Quadratur-Arrayelementen aufgebauten 8-Kanal Phased-Array Spule. Mit dieser wurden im Kernspintomographen NMR-Untersuchungen an Phantomen durchgeführt, die den SNR-Gewinn sowie die signifikante Verbesserung der Kodiereigenschaften durch die Verwendung von Quadratur-Elementen in guter Übereinstimmung mit den Simulationsergebnissen bestätigen konnten. Eine derartige Steigerung der Leistungsfähigkeit eines gewöhnlichen, flachen Spulenarrays durch das Hinzufügen senkrechter, intrinsisch entkoppelter Spulenelemente zeigt sich auch in den Resultaten coronal und sagittal orientierter NMR-Bildgebungsuntersuchungen der Wirbelsäule eines gesunden Probanden. Hierbei sind selbst bei Beschleunigungen von einem Faktor 4 keine Artefakte aufgrund einer schlecht konditionierten parallelen Bildrekonstruktion zu beobachten. N2 - In the presented work, alternative phased-array configurations were investigated. They provide smooth spatial distributions of surface coil sensitivities for 2D accelerated parallel NMR imaging as well as over a higher spatial density of sample-noise dominated coil elements than conventional array geometries. To this end, a novel 16-channel double-spiral array design was compared to a birdcage-like array of two rings with 8 elements each, which is commonly used for NMR studies on the human head in clinical routine. The encoding capabilities and the achievable intrinsic signal-to-noise ratio of the different array structures were determined and compared utilizing Biot-Savart calculations in the development environment Matlab. In addition, geometrical variations in the double-spiral array design were investigated regarding their influence on the intrinsic isolation between the inner +pi twisted and the outer -pi twisted single-spiral array coil. Furthermore, phased-array setups with 32 independent receive elements were evaluated. Within the scope of an experimental evaluation of the double-spiral array coil concept single coil elements of different 16-channel volume array setups were compared, before a double-spiral phased-array prototype coil was constructed. With this prototype the essential intrinsic isolation between both single-spiral coil arrays could be verified as well as the coil sensitivity variations could be demonstrated to be smoothly distributed in all three spatial directions by experiments within the NMR system. Thus a factor 4 accelerated NMR imaging of the human head using a 3D MP-RAGE imaging sequence became possible despite the rather small amount of six independent receive channels. This high acceleration could be achieved for any arbitrary orientation of encoding directions with likewise good image quality and hence proved independent of the desired positioning of the three-dimensional imaging volume. The by this means confirmed concept of a double-spiral array geometry provides not only a smooth sensitivity distribution along all spatial directions but also allows a higher local density of sample-noise dominated single coil elements. In a second approach, the concept of spatial more compacted quadrature array elements was introduced, which are formed by an appropriate geometrical combination of two single surface coil elements. The performance of such an array element configuration was evaluated by a comparison of an 8-channel phased-array coil built out of four quadrature array elements with a conventional 4-channel coil array, which consists of four horizontal coil elements in a row. The encoding capabilities of the individual phased-arrays as well as the available intrinsic SNR were again determined by Biot-Savart simulations in Matlab. They showed that with such a novel element configuration an increased SNR of 30 % can be attained. Moreover, a significant improvement of encoding performance became also apparent in consequence of the doubled number of single coil elements while keeping the basic size of the phased-array structure the same. For experimental evaluation a straightforward 8-channel phased-array coil constructed out of four quadrature array elements was used. So NMR experiments were performed in the NMR system, with which the gain in SNR and the considerable improvement of encoding abilities due to the quadrature elements could be confirmed in close correlation to the simulations. The performance of a common planar coil array, which is similarly enhanced through adding perpendicular, intrinsically decoupled coil elements, is also shown by coronal and sagittal NMR imaging results of the spine of a healthy volunteer. In this case, no image artifacts are recognizable due to ill-conditioned parallel imaging reconstructions even for acceleration of a factor of four. KW - NMR-Bildgebung KW - MR KW - Phased KW - Array KW - Spulen KW - MR KW - phased KW - array KW - coil Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-52399 ER - TY - JOUR A1 - Merget, Benjamin A1 - Koetschan, Christian A1 - Hackl, Thomas A1 - Förster, Frank A1 - Dandekar, Thomas A1 - Müller, Tobias A1 - Schultz, Jörg A1 - Wolf, Matthias T1 - The ITS2 Database JF - Journal of Visual Expression N2 - The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable ITS2 sequence, it confined this marker to low-level phylogenetics only. However, the combination of the ITS2 sequence and its highly conserved secondary structure improves the phylogenetic resolution1 and allows phylogenetic inference at multiple taxonomic ranks, including species delimitation. The ITS2 Database presents an exhaustive dataset of internal transcribed spacer 2 sequences from NCBI GenBank accurately reannotated. Following an annotation by profile Hidden Markov Models (HMMs), the secondary structure of each sequence is predicted. First, it is tested whether a minimum energy based fold (direct fold) results in a correct, four helix conformation. If this is not the case, the structure is predicted by homology modeling. In homology modeling, an already known secondary structure is transferred to another ITS2 sequence, whose secondary structure was not able to fold correctly in a direct fold. The ITS2 Database is not only a database for storage and retrieval of ITS2 sequence-structures. It also provides several tools to process your own ITS2 sequences, including annotation, structural prediction, motif detection and BLAST search on the combined sequence-structure information. Moreover, it integrates trimmed versions of 4SALE and ProfDistS for multiple sequence-structure alignment calculation and Neighbor Joining tree reconstruction. Together they form a coherent analysis pipeline from an initial set of sequences to a phylogeny based on sequence and secondary structure. In a nutshell, this workbench simplifies first phylogenetic analyses to only a few mouse-clicks, while additionally providing tools and data for comprehensive large-scale analyses. KW - homology modeling KW - molecular systematics KW - internal transcribed spacer 2 KW - alignment KW - genetics KW - secondary structure KW - ribosomal RNA KW - phylogenetic tree KW - phylogeny Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124600 VL - 61 IS - e3806 ER - TY - JOUR A1 - Förster, Frank A1 - Beisser, Daniela A1 - Grohme, Markus A. A1 - Liang, Chunguang A1 - Mali, Brahim A1 - Siegl, Alexander Matthias A1 - Engelmann, Julia C. A1 - Shkumatov, Alexander V. A1 - Schokraie, Elham A1 - Müller, Tobias A1 - Schnölzer, Martina A1 - Schill, Ralph O. A1 - Frohme, Marcus A1 - Dandekar, Thomas T1 - Transcriptome analysis in tardigrade species reveals specific molecular pathways for stress adaptations JF - Bioinformatics and biology insights N2 - Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade \(Milnesium\) \(tardigradum\) were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from \(Hypsibius\) \(dujardini\), revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for \(M.\) \(tardigradum\) are different from typical motifs known from higher animals. \(M.\) \(tardigradum\) and \(H.\) \(dujardini\) protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of \(M.\) \(tardigradum\). These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and \(M.\) \(tardigradum\) in particular so highly stress resistant. KW - RNA KW - expressed sequence tag KW - cluster KW - protein familiy KW - adaption KW - tardigrada KW - transcriptome Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123089 N1 - This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited. VL - 6 ER - TY - JOUR A1 - Walter, Maggie C. A1 - Reilich, Peter A1 - Thiele, Simone A1 - Schessl, Joachim A1 - Schreiber, Herbert A1 - Reiners, Karlheinz A1 - Kress, Wolfram A1 - Müller-Reible, Clemens A1 - Vorgerd, Matthias A1 - Urban, Peter A1 - Schrank, Bertold A1 - Deschauer, Marcus A1 - Schlotter-Weigel, Beate A1 - Kohnen, Ralf A1 - Lochmüller, Hans T1 - Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial JF - Orphanet Journal of Rare Diseases N2 - Background: Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). Methods: We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial. After one year of natural course without intervention, 25 patients with genetically defined dysferlinopathy were randomized to receive deflazacort and placebo for six months each (1 mg/kg/day in month one, 1 mg/kg every 2nd day during months two to six) in one of two treatment sequences. Results: During one year of natural course, muscle strength declined about 2% as measured by CIDD (Clinical Investigation of Duchenne Dystrophy) score, and 76 Newton as measured by hand-held dynamometry. Deflazacort did not improve muscle strength. In contrast, there is a trend of worsening muscle strength under deflazacort treatment, which recovers after discontinuation of the study drug. During deflazacort treatment, patients showed a broad spectrum of steroid side effects. Conclusion: Deflazacort is not an effective therapy for dysferlinopathies, and off-label use is not warranted. This is an important finding, since steroid treatment should not be administered in patients with dysferlinopathy, who may be often misdiagnosed as polymyositis. KW - Deflazacort KW - muscle strength KW - gridle muscular-dystrophy KW - Duchenne dystrphy KW - Miyoshi myopathy KW - mutation KW - prednisone KW - gene KW - 2B KW - children KW - design KW - steroids KW - therapy KW - dysferlinopathy KW - Limb girdle muscular dystrophy (LGMD) Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125663 SN - 1750-1172 VL - 8 IS - 26 ER - TY - RPRT A1 - Müller-Brandeck-Bocquet, Gisela A1 - Gieg, Philipp A1 - Lowinger, Timo A1 - Gsänger, Matthias A1 - Becker, Michael A1 - Kundu, Amitabh A1 - Valerian, Rodrigues A1 - S, Shaji A1 - Schömbucher-Kusterer, Elisabeth A1 - Biswas, Aparajita ED - Müller-Brandeck-Bocquet, Gisela ED - Gieg, Philipp ED - Lowinger, Timo T1 - Exploring Emerging India - Eight Essays T1 - Exploring Emerging India - Acht Essays N2 - India's economic rise since the 1990s has been followed by a more prominent global role for the country. Despite economic setbacks in recent years and huge domestic challenges like poverty, caste issues, and gender inequality, India today is almost universally characterised as an “emerging power”. At the same time, the country continues to show an enormous diversity. Thus, exploring emerging India can surely not be confined to economic analysis only. Instead, it is vital to take current developments in domestic and international politics, society, culture, religion, and political thinking into consideration as well. Following an interdisciplinary approach, contributions from Political Science, International Relations, Indology, Political Theory, and Economics are fundamental in order to grasp the country's diversity. This collection assembles eight essays which, individually, serve as working papers reflecting the authors' various research focuses, while collectively composing a multifaceted and multidis-ciplinary picture of emerging India. It thereby reflects the approach the University of Würz-burg’s Centre for Modern India and the Institute for Political Science and Sociology’s India Forum are committed to: bringing together different academic disciplines in order to generate nuanced insights into India’s manifold diversity. N2 - Indiens wirtschaftlicher Aufstieg seit Beginn der 1990er Jahre geht mit einer immer promi-nenteren globalen Rolle des Landes einher. Trotz ökonomischer Rückschläge und gewaltiger innerer Herausforderungen wie Armut, Kastenwesen und Geschlechterungleichheit wird Indi-en heute einhellig als „Emerging Power“ charakterisiert. Gleichzeitig ist das Land weiterhin von enormer Vielfalt geprägt. „Exploring Emerging India“ – dieses Unterfangen kann daher nicht auf wirtschaftliche Aspekte beschränkt bleiben. Unverzichtbar ist vielmehr, auch aktuelle Entwicklungen in Gesellschaft, Kultur, Religion, politischem Denken und nationaler wie internationaler Politik in den Blick zu nehmen. Um die indische Vielfalt zu erfassen, ist daher ein interdisziplinäres Zusammenspiel von Beiträgen aus Politikwissenschaft, Internationalen Beziehungen, Indologie, Politischer Theorie und Wirtschaftswissenschaft essentiell. Dieser Band versammelt acht Essays, die zum einen als Arbeitspapiere die Forschungsschwerpunkte ihrer jeweiligen Autoren widerspiegeln, zum anderen aber in ihrer Gesamtheit ein facettenrei-ches und multidisziplinäres Bild des aufstrebenden Landes zeichnen. Der Band folgt damit dem Ansatz, dem sich das Zentrum Modernes Indien der Universität Würzburg und das Indi-en-Forum des Instituts für Politikwissenschaft und Soziologie verschrieben haben: dem Zu-sammenführen verschiedener akademischer Disziplinen, um differenzierte Einblicke in Indiens reichhaltige Vielfalt zu gewinnen. T3 - Würzburger Arbeitspapiere zur Politikwissenschaft und Soziologie (WAPS) - 7 KW - Indien / Government KW - Indien / Parliament / House of the People KW - BRICS-Staaten KW - Internationale Politik KW - Säkularismus KW - Narendra Modi KW - Emerging Power KW - Political Science KW - Diversity KW - Indian Economy Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119973 ER - TY - JOUR A1 - Biju, Joseph A1 - Schwarz, Roland A1 - Linke, Burkhard A1 - Blom, Jochen A1 - Becker, Anke A1 - Claus, Heike A1 - Goesmann, Alexander A1 - Frosch, Matthias A1 - Müller, Tobias A1 - Vogel, Ulrich A1 - Schoen, Christoph T1 - Virulence Evolution of the Human Pathogen Neisseria meningitidis by Recombination in the Core and Accessory Genome JF - PLoS One N2 - Background Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH) and multilocus sequence typing (MLST) of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences. Principal Findings We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA) island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins. Conclusions Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence. KW - population genetics KW - DNA recombination KW - meningococcal disease KW - recombinant proteins KW - genomic databases KW - comparative genomics KW - neisseria meningitidis KW - homologous recombination Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137960 VL - 6 IS - 4 ER - TY - JOUR A1 - Steinmann, Diana A1 - Paelecke-Habermann, Yvonne A1 - Geinitz, Hans A1 - Aschoff, Raimund A1 - Bayerl, Anja A1 - Bölling, Tobias A1 - Bosch, Elisabeth A1 - Bruns, Frank A1 - Eichenseder-Seiss, Ute A1 - Gerstein, Johanna A1 - Gharbi, Nadine A1 - Hagg, Juliane A1 - Hipp, Matthias A1 - Kleff, Irmgard A1 - Müller, Axel A1 - Schäfer, Christof A1 - Schleicher, Ursula A1 - Sehlen, Susanne A1 - Theodorou, Marilena A1 - Wypior, Hans-Joachim A1 - Zehentmayr, Franz A1 - van Oorschot, Birgitt A1 - Vordermark, Dirk T1 - Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases JF - BMC Cancer N2 - Background: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. Methods: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. Results: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. Conclusions: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information. KW - breast cancer KW - brain tumours KW - survival KW - validation KW - symptoms KW - EORTC-QLQ-C15-PAL KW - EORTC-BN20 KW - whole-brain radiotherapy KW - partitioning analysis RPA KW - cancer patients KW - lung cancer KW - prognostic index KW - radiation oncology KW - clinical trials Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135254 VL - 12 IS - 283 ER - TY - JOUR A1 - Semmler, Anna-Lena A1 - Sacconi, Sabrina A1 - Bach, J. Elisa A1 - Liebe, Claus A1 - Bürmann, Jan A1 - Kley, Rudolf A. A1 - Ferbert, Andreas A1 - Anderheiden, Roland A1 - Van den Bergh, Peter A1 - Martin, Jean-Jacques A1 - De Jonghe, Peter A1 - Neuen-Jacob, Eva A1 - Müller, Oliver A1 - Deschauer, Marcus A1 - Bergmann, Markus A1 - Schröder, J. Michael A1 - Vorgerd, Matthias A1 - Schulz, Jörg B. A1 - Weis, Joachim A1 - Kress, Wolfram A1 - Claeys, Kristl G. T1 - Unusual multisystemic involvement and a novel BAG3 mutation revealed by NGS screening in a large cohort of myofibrillar myopathies JF - Orphanet Journal of Rare Diseases N2 - Background: Myofibrillar myopathies (MFM) are a group of phenotypically and genetically heterogeneous neuromuscular disorders, which are characterized by protein aggregations in muscle fibres and can be associated with multisystemic involvement. Methods: We screened a large cohort of 38 index patients with MFM for mutations in the nine thus far known causative genes using Sanger and next generation sequencing (NGS). We studied the clinical and histopathological characteristics in 38 index patients and five additional relatives (n = 43) and particularly focused on the associated multisystemic symptoms. Results: We identified 14 heterozygous mutations (diagnostic yield of 37%), among them the novel p. Pro209Gln mutation in the BAG3 gene, which was associated with onset in adulthood, a mild phenotype and an axonal sensorimotor polyneuropathy, in the absence of giant axons at the nerve biopsy. We revealed several novel clinical phenotypes and unusual multisystemic presentations with previously described mutations: hearing impairment with a FLNC mutation, dysphonia with a mutation in DES and the first patient with a FLNC mutation presenting respiratory insufficiency as the initial symptom. Moreover, we described for the first time respiratory insufficiency occurring in a patient with the p. Gly154Ser mutation in CRYAB. Interestingly, we detected a polyneuropathy in 28% of the MFM patients, including a BAG3 and a MYOT case, and hearing impairment in 13%, including one patient with a FLNC mutation and two with mutations in the DES gene. In four index patients with a mutation in one of the MFM genes, typical histological findings were only identified at the ultrastructural level (29%). Conclusions: We conclude that extraskeletal symptoms frequently occur in MFM, particularly cardiac and respiratory involvement, polyneuropathy and/or deafness. BAG3 mutations should be considered even in cases with a mild phenotype or an adult onset. We identified a genetic defect in one of the known genes in less than half of the MFM patients, indicating that more causative genes are still to be found. Next generation sequencing techniques should be helpful in achieving this aim. KW - polyneuropathy KW - MFM KW - next generation sequencing KW - bcl-2 associated athanogene protein 3 KW - protein aggregation KW - hearing impairment KW - early respiratory-failure KW - myopathy KW - muscular-dystrophy KW - skeletal myopathy Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115623 SN - 1750-1172 N1 - Additional files are available here: http://www.ojrd.com/content/9/1/121/additional VL - 9 IS - 121 ER - TY - JOUR A1 - Morris, E. Kathryn A1 - Caruso, Tancredi A1 - Buscot, Francois A1 - Fischer, Markus A1 - Hancock, Christine A1 - Maier, Tanja S. A1 - Meiners, Torsten A1 - Müller, Caroline A1 - Obermaier, Elisabeth A1 - Prati, Daniel A1 - Socher, Stephanie A. A1 - Sonnemann, Ilja A1 - Wäschke, Nicola A1 - Wubet, Tesfaye A1 - Wurst, Susanne A1 - Rillig, Matthias C. T1 - Choosing and using diversity indices: insights for ecological applications from the German Biodiversity Exploratories JF - Ecology and Evolution N2 - Biodiversity, a multidimensional property of natural systems, is difficult to quantify partly because of the multitude of indices proposed for this purpose. Indices aim to describe general properties of communities that allow us to compare different regions, taxa, and trophic levels. Therefore, they are of fundamental importance for environmental monitoring and conservation, although there is no consensus about which indices are more appropriate and informative. We tested several common diversity indices in a range of simple to complex statistical analyses in order to determine whether some were better suited for certain analyses than others. We used data collected around the focal plant Plantago lanceolata on 60 temperate grassland plots embedded in an agricultural landscape to explore relationships between the common diversity indices of species richness (S), Shannon's diversity (H'), Simpson's diversity (D-1), Simpson's dominance (D-2), Simpson's evenness (E), and Berger-Parker dominance (BP). We calculated each of these indices for herbaceous plants, arbuscular mycorrhizal fungi, aboveground arthropods, belowground insect larvae, and P.lanceolata molecular and chemical diversity. Including these trait-based measures of diversity allowed us to test whether or not they behaved similarly to the better studied species diversity. We used path analysis to determine whether compound indices detected more relationships between diversities of different organisms and traits than more basic indices. In the path models, more paths were significant when using H', even though all models except that with E were equally reliable. This demonstrates that while common diversity indices may appear interchangeable in simple analyses, when considering complex interactions, the choice of index can profoundly alter the interpretation of results. Data mining in order to identify the index producing the most significant results should be avoided, but simultaneously considering analyses using multiple indices can provide greater insight into the interactions in a system. KW - molecular diversity KW - plant diversity KW - plantago lanceolata KW - shannon index KW - simpson's index KW - arbuscular mycorrhizal fungi KW - Hill's powers KW - chemical diversity KW - Berger-Parker KW - arthropods Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115462 SN - 2045-7758 VL - 4 IS - 18 ER - TY - JOUR A1 - Koetschan, Christian A1 - Kittelmann, Sandra A1 - Lu, Jingli A1 - Al-Halbouni, Djamila A1 - Jarvis, Graeme N. A1 - Müller, Tobias A1 - Wolf, Matthias A1 - Janssen, Peter H. T1 - Internal Transcribed Spacer 1 Secondary Structure Analysis Reveals a Common Core throughout the Anaerobic Fungi (Neocallimastigomycota) JF - PLOS ONE N2 - The internal transcribed spacer (ITS) is a popular barcode marker for fungi and in particular the ITS1 has been widely used for the anaerobic fungi (phylum Neocallimastigomycota). A good number of validated reference sequences of isolates as well as a large number of environmental sequences are available in public databases. Its highly variable nature predisposes the ITS1 for low level phylogenetics; however, it complicates the establishment of reproducible alignments and the reconstruction of stable phylogenetic trees at higher taxonomic levels (genus and above). Here, we overcame these problems by proposing a common core secondary structure of the ITS1 of the anaerobic fungi employing a Hidden Markov Model-based ITS1 sequence annotation and a helix-wise folding approach. We integrated the additional structural information into phylogenetic analyses and present for the first time an automated sequence-structure-based taxonomy of the ITS1 of the anaerobic fungi. The methodology developed is transferable to the ITS1 of other fungal groups, and the robust taxonomy will facilitate and improve high-throughput anaerobic fungal community structure analysis of samples from various environments. KW - profile distances KW - ITS2 KW - phylogenetic trees KW - RNA sequence KW - reconstruction KW - diversity KW - populations KW - tool KW - systematics KW - herbivores Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117058 VL - 9 IS - 3 ER - TY - JOUR A1 - Peter, Stefanie A1 - Bultinck, Jennyfer A1 - Myant, Kevin A1 - Jaenicke, Laura A. A1 - Walz, Susanne A1 - Müller, Judith A1 - Gmachl, Michael A1 - Treu, Matthias A1 - Boehmelt, Guido A1 - Ade, Casten P. A1 - Schmitz, Werner A1 - Wiegering, Armin A1 - Otto, Christoph A1 - Popov, Nikita A1 - Sansom, Owen A1 - Kraut, Norbert A1 - Eilers, Martin T1 - H Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase JF - EMBO Molecular Medicine N2 - Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARF-BP1, MULE) associates with both MYC and the MYC-associated protein MIZ1. We show here that HUWE1 is required for growth of colorectal cancer cells in culture and in orthotopic xenograft models. Using high-throughput screening, we identify small molecule inhibitors of HUWE1, which inhibit MYC-dependent transactivation in colorectal cancer cells, but not in stem and normal colon epithelial cells. Inhibition of HUWE1 stabilizes MIZ1. MIZ1 globally accumulates on MYC target genes and contributes to repression of MYC-activated target genes upon HUWE1 inhibition. Our data show that transcriptional activation by MYC in colon cancer cells requires the continuous degradation of MIZ1 and identify a novel principle that allows for inhibition of MYC function in tumor cells. KW - colorectal cancer KW - HUWE1 KW - MIZ1 KW - MYC KW - ubiquitination KW - cancer KW - digestive system KW - pharmacology KW - drug discovery Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118132 SN - 1757-4684 VL - 6 IS - 12 ER - TY - JOUR A1 - Wolf, Matthias A1 - Chen, Shilin A1 - Song, Jingyuan A1 - Ankenbrand, Markus A1 - Müller, Tobias T1 - Compensatory Base Changes in ITS2 Secondary Structures Correlate with the Biological Species Concept Despite Intragenomic Variability in ITS2 Sequences – A Proof of Concept JF - PLoS ONE N2 - Compensatory base changes (CBCs) in internal transcribed spacer 2 (ITS2) rDNA secondary structures correlate with Ernst Mayr’s biological species concept. This hypothesis also referred to as the CBC species concept recently was subjected to large-scale testing, indicating two distinct probabilities. (1) If there is a CBC then there are two different species with a probability of ~0.93. (2) If there is no CBC then there is the same species with a probability of ~0.76. In ITS2 research, however, the main problem is the multicopy nature of ITS2 sequences. Most recently, 454 pyrosequencing data have been used to characterize more than 5000 intragenomic variations of ITS2 regions from 178 plant species, demonstrating that mutation of ITS2 is frequent, with a mean of 35 variants per species, respectively per individual organism. In this study, using those 454 data, the CBC criterion is reconsidered in the light of intragenomic variability, a proof of concept, a necessary criterion, expecting no intragenomic CBCs in variant ITS2 copies. In accordance with the CBC species concept, we could demonstrate that the probability that there is no intragenomic CBC is ~0.99. KW - citrus KW - concerted evolution KW - DNA sequences KW - Genome evolution KW - Phylogenetics KW - plant evolution KW - sequence alignment KW - sequence databases Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96450 ER - TY - JOUR A1 - Sweeney, Reinhart A. A1 - Seubert, Benedikt A1 - Stark, Silke A1 - Homann, Vanessa A1 - Müller, Gerd A1 - Flentje, Michael A1 - Guckenbeger, Matthias T1 - Accuracy and inter-observer variability of 3D versus 4D cone-beam CT based image-guidance in SBRT for lung tumors N2 - Background: To analyze the accuracy and inter-observer variability of image-guidance (IG) using 3D or 4D cone-beam CT (CBCT) technology in stereotactic body radiotherapy (SBRT) for lung tumors. Materials and methods: Twenty-one consecutive patients treated with image-guided SBRT for primary and secondary lung tumors were basis for this study. A respiration correlated 4D-CT and planning contours served as reference for all IG techniques. Three IG techniques were performed independently by three radiation oncologists (ROs) and three radiotherapy technicians (RTTs). Image-guidance using respiration correlated 4D-CBCT (IG-4D) with automatic registration of the planning 4D-CT and the verification 4D-CBCT was considered gold-standard. Results were compared with two IG techniques using 3D-CBCT: 1) manual registration of the planning internal target volume (ITV) contour and the motion blurred tumor in the 3D-CBCT (IG-ITV); 2) automatic registration of the planning reference CT image and the verification 3D-CBCT (IG-3D). Image quality of 3D-CBCT and 4D-CBCT images was scored on a scale of 1–3, with 1 being best and 3 being worst quality for visual verification of the IGRT results. Results: Image quality was scored significantly worse for 3D-CBCT compared to 4D-CBCT: the worst score of 3 was given in 19 % and 7.1 % observations, respectively. Significant differences in target localization were observed between 4D-CBCT and 3D-CBCT based IG: compared to the reference of IG-4D, tumor positions differed by 1.9 mm± 0.9 mm (3D vector) on average using IG-ITV and by 3.6 mm± 3.2 mm using IG-3D; results of IG-ITV were significantly closer to the reference IG-4D compared to IG-3D. Differences between the 4D-CBCT and 3D-CBCT techniques increased significantly with larger motion amplitude of the tumor; analogously, differences increased with worse 3D-CBCT image quality scores. Inter-observer variability was largest in SI direction and was significantly larger in IG using 3D-CBCT compared to 4D-CBCT: 0.6 mm versus 1.5 mm (one standard deviation). Inter-observer variability was not different between the three ROs compared to the three RTTs. Conclusions: Respiration correlated 4D-CBCT improves the accuracy of image-guidance by more precise target localization in the presence of breathing induced target motion and by reduced inter-observer variability. KW - Medizin KW - Lung cancer KW - Image-guidance KW - Cone-beam CT KW - Inter-observer variability KW - Respiration correlated imaging Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75698 ER - TY - THES A1 - Müller, Matthias T1 - Vergleich von in-vitro-Ergebnissen im Mikrokerntest und den klinischen Beobachtungen nach Bestrahlung T1 - Comparison of in-vitro-results in micronucleus-assay and clinical observations after radiotherapy N2 - Hintergrund: Mikrokerne sind Chromosomenfragmente, die nicht in den Hauptkern integriert wurden und im Zytoplasma von proliferierenden Zellen nach ionisierender Strahlung oder Behandlung mit mutagensierenden Substanzen zu finden sind. In vielen Fällen konnte gezeigt werden, dass die Mikrokernfrequenz als Indikator für den strahleninduzierten Schaden dienen kann. Humane Lymphozyten und Fibroblasten von Patientinnen mit Brustkrebs nach Brusterhaltender Therapie wurden bestrahlt, im Mikrokerntest ausgewertet und die Ergebnisse mit den klinischen Akutreaktionen verglichen. Methode: Beide Zelltypen der 24 Patientinnen mit dem selben Bestrahlungsproceder (50 Gy + 10 Gy Boost) und ohne Chemotherapie wurden untersucht. Die Normalgewebsreaktionen wurden unter Verwendung der RTOG-Kriterien bestimmt. Die Zellen wurden in vitro mit 0-, 1-, 2-Gy-Einmaldosis-Bestrahlung (Lymphozyten) bzw. 0-, 2-, 4-Gy-Einmaldosis-Bestrahlung behandelt, über 72 h kultiviert, auf Objektträgern fixiert und bei 400 - 1000facher Vergrößerung (Fluoreszenzmikroskop) ausgewertet. Die Zellteilung der Lymphozyten wurde mittels Cytochalasin B (Cyt B) inhibiert. Ergebnisse: Es konnte keine signifikante Korrelation der in-vitro-Strahlenempfindlichkeit und den Normalgewebsreaktionen beobachtet werden. Des weiteren wurde kein Zusammenhang zwischen der Strahlenempfindlichkeit der lymphozyten und den Fibroblasten, die vom selben Spender gewonnen wurden, beobachtet. Zusammenfassung: Die Daten unterstützen nicht den Nutzen des Mikrokern-Testes in der Vorhersage von Normalgewebsreaktionen auf die Strahlentherapie bei Malignompatienten. N2 - Comparison of in-vitro-results in micronucleus-assay (MN-assay) and clinical observations after radiotherapy Background: Micronuclei are chromosome fragments which are not integrated into the main nucleus and expressed in cytoplasm of proliferating cells after ionizing radiation or treatment with mutagenic agents. In many cases it has been shown that the micronucleus frequence can be a indicator of cellular radiation induced damage. Human lymphocytes and fibroblasts of patients with breast cancer after breast conserving therapy were irradiated, tested in MN-assay and the results were compared with clinical acute reactions. Methods: Both celltypes of 24 patients with the same irradiation procedure (50 Gy + 10 Gy boost) and without chemotherapy were observed. The acute reactions of normal tissue were determined by using the RTOG scale. The cells were treated in vitro with 0-, 1- and 2-Gy-single-dose-irradiation (lymphocytes) or with 0-, 2-and 4-Gy-single-dose-irradiation (fibroblasts) respectively, cultured about 72 h, fixed on slides and scored at 400 - 1000x magnification (flourescence microscope). The cellular division of lymphocytes was inhibited by using Cytochalasin B (Cyt B). Results: No significant correlation of in-vitro-radiosensivity and normal tissue reactions were observed. In addition, no relationship was observed between the radiosensitivity of lymphocytes and fibroblasts derived from the same donors. Conclusion: The data does not support the usefulness of the MN-assay in predicting normal-tissue response to radiotherapy of cancer patients. KW - Mikrokerntest KW - Strahlentherapie KW - Brustkrebs KW - Lymphozyten KW - Fibroblasten KW - micronucleus-assay KW - radiotherapy KW - breastcancer KW - lymphocytes KW - fibroblasts Y1 - 2004 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-10212 ER - TY - JOUR A1 - Karimi, Sohail M. A1 - Freund, Matthias A1 - Wager, Brittney M. A1 - Knoblauch, Michael A1 - Fromm, Jörg A1 - M. Mueller, Heike A1 - Ache, Peter A1 - Krischke, Markus A1 - Mueller, Martin J. A1 - Müller, Tobias A1 - Dittrich, Marcus A1 - Geilfus, Christoph-Martin A1 - Alfaran, Ahmed H. A1 - Hedrich, Rainer A1 - Deeken, Rosalia T1 - Under salt stress guard cells rewire ion transport and abscisic acid signaling JF - New Phytologist N2 - Soil salinity is an increasingly global problem which hampers plant growth and crop yield. Plant productivity depends on optimal water-use efficiency and photosynthetic capacity balanced by stomatal conductance. Whether and how stomatal behavior contributes to salt sensitivity or tolerance is currently unknown. This work identifies guard cell-specific signaling networks exerted by a salt-sensitive and salt-tolerant plant under ionic and osmotic stress conditions accompanied by increasing NaCl loads. We challenged soil-grown Arabidopsis thaliana and Thellungiella salsuginea plants with short- and long-term salinity stress and monitored genome-wide gene expression and signals of guard cells that determine their function. Arabidopsis plants suffered from both salt regimes and showed reduced stomatal conductance while Thellungiella displayed no obvious stress symptoms. The salt-dependent gene expression changes of guard cells supported the ability of the halophyte to maintain high potassium to sodium ratios and to attenuate the abscisic acid (ABA) signaling pathway which the glycophyte kept activated despite fading ABA concentrations. Our study shows that salinity stress and even the different tolerances are manifested on a single cell level. Halophytic guard cells are less sensitive than glycophytic guard cells, providing opportunities to manipulate stomatal behavior and improve plant productivity. KW - soil KW - stomata KW - abscisic acid (ABA) KW - glycophyte Arabidopsis KW - guard cell KW - halophyte Thellungiella/Eutrema KW - ion transport KW - salt stress Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259635 VL - 231 IS - 3 ER - TY - JOUR A1 - Temme, Fabian A1 - Adam, Jan A1 - Ahnen, Max L. A1 - Baack, Dominik A1 - Balbo, Matteo A1 - Bergmann, Matthias A1 - Biland, Adrian A1 - Blank, Michael A1 - Bretz, Thomas A1 - Brügge, Kai A. A1 - Buss, Jens A1 - Dmytriiev, Anton A1 - Dorner, Daniela A1 - Einecke, Sabrina A1 - Hempfling, Christina A1 - Hildebrand, Dorothee A1 - Hughes, Gareth A1 - Linhoff, Lena A1 - Mannheim, Karl A1 - Müller, Sebastian A1 - Neise, Dominik A1 - Neronov, Andrii A1 - Nöthe, Max A1 - Paravac, Aleksander A1 - Pauss, Felicitas A1 - Rhode, Wolfgang A1 - Shukla, Amit A1 - Thaele, Julia A1 - Walter, Roland T1 - Long-Term monitoring of bright blazars in the multi-GeV to TeV range with FACT JF - Galaxies N2 - Blazars like Markarian 421 or Markarian 501 are active galactic nuclei (AGN), with their jets orientated towards the observer. They are among the brightest objects in the very high energy (VHE) gamma ray regime (>100 GeV). Their emitted gamma-ray fluxes are extremely variable, with changing activity levels on timescales between minutes, months, and even years. Several questions are part of the current research, such as the question of the emission regions or the engine of the AGN and the particle acceleration. A dedicated longterm monitoring program is necessary to investigate the properties of blazars in detail. A densely sampled and unbiased light curve allows for observation of both high and low states of the sources, and the combination with multi-wavelength observation could contribute to the answer of several questions mentioned above. FACT (First G-APD Cherenkov Telescope) is the first operational telescope using silicon photomultiplier (SiPM, also known as Geigermode—Avalanche Photo Diode, G-APD) as photon detectors. SiPM have a very homogenous and stable longterm performance, and allow operation even during full moon without any filter, leading to a maximal duty cycle for an Imaging Air Cherenkov Telescope (IACT). Hence, FACT is an ideal device for such a longterm monitoring of bright blazars. A small set of sources (e.g., Markarian 421, Markarian 501, 1ES 1959+650, and 1ES 2344+51.4) is currently being monitored. In this contribution, the FACT telescope and the concept of longterm monitoring of bright blazars will be introduced. The results of the monitoring program will be shown, and the advantages of densely sampled and unbiased light curves will be discussed. KW - Imaging Air Cherenkov Telescope KW - First G-APD Cherenkov Telescope KW - very high energy gamma rays KW - long-term monitoring KW - silicon photo multiplier Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198088 SN - 2075-4434 VL - 5 IS - 1 PB - MDPI ER -