@article{AbuHalimaHaeuslerBackesetal.2017,
  author    = {Abu-Halima, Masood and H{\"a}usler, Sebastian and Backes, Christina and Fehlmann, Tobias and Staib, Claudia and Nestel, Sigrun and Nazarenko, Irina and Meese, Eckart and Keller, Andreas},
  title     = {Micro-ribonucleic acids and extracellular vesicles repertoire in the spent culture media is altered in women undergoing \(In\) \(Vitro\) Fertilization},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-017-13683-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173632},
  year      = {2017},
  abstract  = {MicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene regulation. We analyzed the potential of miRNAs secreted from pre-implantation embryos into the embryonic culture media as biomarkers to predict successful pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the SCM. On average, we detected 163 miRNAs in SCM of samples with failed pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634 predicted an embryo transfer leading to a positive pregnancy with an accuracy of 71\% and a sensitivity of 85\%. Among the 621 miRNAs, 102 (16.4\%) showed a differential expression between positive and negative outcome of pregnancy with miR-29c-3p as the most significantly differentially expressed miRNA. The number of extracellular vehicles was lower in SCM with positive outcomes (3.8 × 10\(^9\)/mL EVs), as compared to a negative outcome (7.35 × 10\(^9\)/mL EVs) possibly explaining the reduced number of miRNAs in the SCM associated with failed pregnancies. The analysis of the miRNome in the SCM of couples undergoing fertility treatment lays the ground towards development of biomarkers to predict successful pregnancy and towards understanding the role of embryonic miRNAs found in the SCM.},
  language  = {en}
}
@article{AdrianMartinezAlbertAndreetal.2017,
  author    = {Adri{\´a}n-Mart{\´i}nez, S. and Albert, A. and Andr{\´e}, M. and Anghinolfi, M. and Anton, G. and Ardid, M. and Aubert, J.-J. and Baret, B. and Barrios-Marti, J. and Basa, S. and Bertin, V. and Biagi, S. and Bormuth, R. and Bouwhuis, M.C. and Bruijn, R. and Brunner, J. and Buto, J. and Capone, A. and Caramete, L. and Carr, J. and Chiarusi, T. and Circella, M. and Coniglione, R. and Costantini, H. and Coyle, P. and Creusot, A. and Dekeyser, I. and Deschamps, A. and De Bonis, G. and Distefano, C.},
  title     = {Stacked search for time shifted high energy neutrinos from gamma ray bursts with the ANTARES neutrino telescope},
  series = {European Physical Journal C},
  volume    = {77},
  journal   = {European Physical Journal C},
  number    = {1},
  doi       = {10.1140/epjc/s10052-016-4496-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181251},
  pages     = {10},
  year      = {2017},
  abstract  = {A search for high-energy neutrino emission correlated with gamma-ray bursts outside the electromagnetic prompt-emission time window is presented. Using a stacking approach of the time delays between reported gamma-ray burst alerts and spatially coincident muon-neutrino signatures, data from the Antares neutrino telescope recorded between 2007 and 2012 are analysed. One year of public data from the IceCube detector between 2008 and 2009 have been also investigated. The respective timing profiles are scanned for statistically significant accumulations within 40 days of the Gamma Ray Burst, as expected from Lorentz Invariance Violation effects and some astrophysical models. No significant excess over the expected accidental coincidence rate could be found in either of the two data sets. The average strength of the neutrino signal is found to be fainter than one detectable neutrino signal per hundred gamma-ray bursts in the Antares data at 90\% confidence level.},
  language  = {en}
}
@article{AeschlimannBrixnerCinchettietal.2017,
  author    = {Aeschlimann, Martin and Brixner, Tobias and Cinchetti, Mirko and Frisch, Benjamin and Hecht, Bert and Hensen, Matthias and Huber, Bernhard and Kramer, Christian and Krauss, Enno and Loeber, Thomas H. and Pfeiffer, Walter and Piecuch, Martin and Thielen, Philip},
  title     = {Cavity-assisted ultrafast long-range periodic energy transfer between plasmonic nanoantennas},
  series = {Light: Science \& Applications},
  volume    = {6},
  journal   = {Light: Science \& Applications},
  doi       = {10.1038/lsa.2017.111},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173265},
  year      = {2017},
  abstract  = {Radiationless energy transfer is at the core of diverse phenomena, such as light harvesting in photosynthesis\(^1\), energy-transfer-based microspectroscopies\(^2\), nanoscale quantum entanglement\(^3\) and photonic-mode hybridization\(^4\). Typically, the transfer is efficient only for separations that are much shorter than the diffraction limit. This hampers its application in optical communication and quantum information processing, which require spatially selective addressing. Here, we demonstrate highly efficient radiationless coherent energy transfer over a distance of twice the excitation wavelength by combining localized and delocalized\(^5\) plasmonic modes. Analogous to the Tavis-Cummings model, two whispering-gallery-mode antennas\(^6\) placed in the foci of an elliptical plasmonic cavity\(^7\) fabricated from single-crystal gold plates act as a pair of oscillators coupled to a common cavity mode. Time-resolved two-photon photoemission electron microscopy (TR 2P-PEEM) reveals an ultrafast long-range periodic energy transfer in accordance with the simulations. Our observations open perspectives for the optimization and tailoring of mesoscopic energy transfer and long-range quantum emitter coupling.},
  language  = {en}
}
@article{AhmedOjhaHirschetal.2017,
  author    = {Ahmed, Bilal and Ojha, Animesh K. and Hirsch, Florian and Fischer, Ingo and Patrice, Donfack and Materny, Arnulf},
  title     = {Tailoring of enhanced interfacial polarization in WO\(_3\) nanorods grown over reduced graphene oxide synthesized by a one-step hydrothermal method},
  series = {RSC Advances},
  volume    = {7},
  journal   = {RSC Advances},
  number    = {23},
  doi       = {10.1039/c7ra00730b},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181829},
  pages     = {13985-13996},
  year      = {2017},
  abstract  = {In the present report, well-defined WO3 nanorods (NRs) and a rGO-WO\(_3\) composite were successfully synthesized using a one-pot hydrothermal method. The crystal phase, structural morphology, shape, and size of the as-synthesized samples were studied using X-ray diffraction (XRD) and transmission electron microscopy (TEM) measurements. The optical properties of the synthesized samples were investigated by Raman, ultraviolet-visible (UV-Vis) and photoluminescence (PL) spectroscopy. Raman spectroscopy and TEM results validate the formation of WO\(_3\) (NRs) on the rGO sheet. The value of the dielectric constant (ε′) of WO3 NRs and rGO-WO\(_3\) composite is decreased with an increase in frequency. At low frequency (2.5 to 3.5 Hz), the value of ε′ for the rGO-WO3 composite is greater than that of pure WO\(_3\) NRs. This could be due to the fact that the induced charges follow the ac signal. However, at higher frequency (3.4 to 6.0), the value of ε′ for the rGO-WO\(_3\) composite is less compared to that of the pure WO3 NRs. The overall decrease in the value of ε′ could be due to the occurrence of a polarization process at the interface of the rGO sheet and WO3 NRs. Enhanced interfacial polarization in the rGO-WO\(_3\) composite is observed, which may be attributed to the presence of polar functional groups on the rGO sheet. These functional groups trap charge carriers at the interface, resulting in an enhancement of the interfacial polarization. The value of the dielectric modulus is also calculated to further confirm this enhancement. The values of the ac conductivity of the WO\(_3\) NRs and rGO-WO\(_3\) composite were calculated as a function of the frequency. The greater value of the ac conductivity in the rGO-WO\(_3\) composite compared to that of the WO\(_3\) NRs confirms the restoration of the sp:\(^{++}\) network during the in situ synthesis of the rGO-WO\(_3\) composite, which is well supported by the results obtained by Raman spectroscopy.},
  language  = {en}
}
@article{AichAkhundzadahKnuerretal.2017,
  author    = {Aich, Valentin and Akhundzadah, Noor Ahmad and Knuerr, Alec and Khoshbeen, Ahmad Jamshed and Hattermann, Fred and Paeth, Heiko and Scanlon, Andrew and Paton, Eva Nora},
  title     = {Climate change in Afghanistan deduced from reanalysis and coordinated regional climate downscaling experiment (CORDEX)—South Asia Simulations},
  series = {Climate},
  volume    = {5},
  journal   = {Climate},
  number    = {2},
  issn      = {2225-1154},
  doi       = {10.3390/cli5020038},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198024},
  pages     = {38},
  year      = {2017},
  abstract  = {Past and the projected future climate change in Afghanistan has been analyzed systematically and differentiated with respect to its different climate regions to gain some first quantitative insights into Afghanistan's vulnerability to ongoing and future climate changes. For this purpose, temperature, precipitation and five additional climate indices for extremes and agriculture assessments (heavy precipitation; spring precipitation; growing season length (GSL), the Heat Wave Magnitude Index (HWMI); and the Standardized Precipitation Evapotranspiration Index (SPEI)) from the reanalysis data were examined for their consistency to identify changes in the past (data since 1950). For future changes (up to the year 2100), the same parameters were extracted from an ensemble of 12 downscaled regional climate models (RCM) of the Coordinated Regional Climate Downscaling Experiment (CORDEX)-South Asia simulations for low and high emission scenarios (Representative Concentration Pathways 4.5 and 8.5). In the past, the climatic changes were mainly characterized by a mean temperature increase above global level of 1.8 °C from 1950 to 2010; uncertainty with regard to reanalyzed rainfall data limited a thorough analysis of past changes. Climate models projected the temperature trend to accelerate in the future, depending strongly on the global carbon emissions (2006-2050 Representative Concentration Pathways 4.5/8.5: 1.7/2.3 °C; 2006-2099: 2.7/6.4 °C, respectively). Despite the high uncertainty with regard to precipitation projections, it became apparent that the increasing evapotranspiration is likely to exacerbate Afghanistan's already existing water stress, including a very strong increase of frequency and magnitude of heat waves. Overall, the results show that in addition to the already extensive deficiency in adaptation to current climate conditions, the situation will be aggravated in the future, particularly in regard to water management and agriculture. Thus, the results of this study underline the importance of adequate adaptation to climate change in Afghanistan. This is even truer taking into account that GSL is projected to increase substantially by around 20 days on average until 2050, which might open the opportunity for extended agricultural husbandry or even additional harvests when water resources are properly managed.},
  language  = {en}
}
@phdthesis{AlHazza2017,
  author    = {Al-Hazza, Aseel},
  title     = {Zu Grad, Konfiguration und Verlauf der Schallempfindungsschwerh{\"o}rigkeit bei Kindern mit einer Connexin-26-Mutation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150966},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Verschiedene Forschungsergebnisse der letzten zehn Jahre ergaben, dass die weitaus h{\"a}ufigeren, nicht-syndromalen Schwerh{\"o}rigkeiten durch Mutation eines Gens (GJB2-Gen) entstehen, welches im Cortischen Organ des Innenohrs exprimiert wird. Das GJB2-Gen (Connexin-26-Gen), dessen Ver{\"a}nderung etwa 50 \% der F{\"a}lle von autosomal rezessiver Schwerh{\"o}rigkeit ausmacht, liegt im Chromosomenbereich 13q11-12. Aktuell identifiziert sind mehr als 70 weitere Loki, die in Verbindung mit nicht-syndromalen Formen von Schwerh{\"o}rigkeit stehen. Die Pr{\"a}valenz von NSHL betr{\"a}gt nach neusten Studien ca. 1,33 pro 1000 Neugeborenen. In W{\"u}rzburg wurden bis zum Jahr 2011 auf der Neugeborenenstation der Frauenklinik der Universit{\"a}tsklinik in einem bew{\"a}hrten zweistufigen Neugeborenen-H{\"o}rscreening ca. 12853 Babys untersucht. Ziel des Neugeborenen-H{\"o}rscreenings ist eine fr{\"u}hestm{\"o}gliche Erkennung von Schwerh{\"o}rigkeit bei Neugeborenen, damit durch die Behandlung eine ungehinderte Sprachentwicklung gew{\"a}hrleistet werden kann. In dieser Arbeit wurde der Zusammenhang zwischen der Mutation im Connexin-26-Gen und dem Grad, dem Verlauf und der Konfiguration der H{\"o}rminderung untersucht. Hierf{\"u}r wurden 59 Patienten im Alter von 1 bis 15 Jahren mit beidseitigen, nicht-syndromalen H{\"o}rst{\"o}rungen der Schallempfindung verschiedenen Grades rekrutiert. Mithilfe der molekulargenetischen Befunde konnten Ver{\"a}nderungen im Connexin-26-Gen diagnostiziert werden. Anschließend wurde versucht, unter Zuhilfenahme aller vorhandenen Befunde der individuellen Audiogramm- und BERA- oder ASSR-Befunde eine Genotyp-Ph{\"a}notyp-Korrelation abzuleiten.},
  subject      = {Connexin-26-Mutation},
  language  = {de}
}
@phdthesis{Ali2017,
  author    = {Ali, Qasim},
  title     = {Distributed Control of Cooperating Mini UAVs},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140686},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Mini Unmanned Aerial Vehicles (MUAVs) werden immer beliebtere Forschungsplattformen. Vor allem in den letzten Jahren ziehen sie aufgrund ihrer Erschwinglichkeit und ihrer Flexibilit{\"a}t, die es erlaubt sie in fast allen Lebensbereichen einzusetzen, betr{\"a}chtliche Aufmerksamkeit auf sich. MUAVs haben offensichtliche Vorteile gegen{\"u}ber bemannten Plattformen einschließlich ihrer viel geringeren Herstellungs- und Betriebskosten, Risikovermeidung f{\"u}r den menschlichen Piloten, der M{\"o}glichkeit sicher niedrig und langsam fliegen zu k{\"o}nnen, und Realisierung von Operationen, die {\"u}ber die inh{\"a}renten Grenzen des menschlichen K{\"o}rpers hinausgehen. Der Fortschritt in der Micro Electro-Mechanical System (MEMS) Technologie, Avionik und Miniaturisierung von Sensoren spielte auch eine bedeutende Rolle bei der Entwicklung der MUAVs. Diese Flugger{\"a}te reichen von einfachem Spielzeug aus dem Elektrofachhandel bis zu hoch entwickelten, kommerziellen Plattformen, die die Durchf{\"u}hrung neuer Aufgaben wie Offshore-Windkraftwerk Inspektionen, 3D-Modellierung von Geb{\"a}uden usw. erlauben. MUAVs sind auch umweltfreundlich, da sie weniger Luftverschmutzung und L{\"a}rm verursachen. Unbemannt ist daher un{\"u}bertroffen. Aktuelle Forschung konzentriert sich auf die M{\"o}glichkeit mehrere kosteng{\"u}nstige Flugger{\"a}te zusammen fliegen zu lassen, w{\"a}hrend die erforderliche relative r{\"a}umliche Trennungen beibehalten wird. Dies erm{\"o}glicht es effizient Aufgaben zu erf{\"u}llen im Vergleich zu einem einzigen sehr teuren Flugger{\"a}t. Durch die Redundanz entf{\"a}llt auch das Risiko des Scheiterns der Mission durch den Verlust eines einzigen Flugger{\"a}ts. Wertvolle Aufgaben, die kooperative Flugger{\"a}te ausf{\"u}hren k{\"o}nnen, sind beispielsweise gemeinsame Lasttransporte, Such- und Rettungsmissionen, mobile Kommunikationsrelais, Spr{\"u}hen von Pestiziden und Wetterbeobachtung. Obwohl die Realisierung von Fl{\"u}gen mit mehreren, gekoppelten UAVs komplex ist, rechtfertigen dennoch offensichtliche Vorteile diese m{\"u}hsame und aufw{\"a}ndige Entwicklungsarbeit. Verteilte Steuerung von kooperierenden Einheiten ist ein multidisziplin{\"a}res Thema, das es erfordert in diversifizierten Bereichen zu arbeiten. Dazu geh{\"o}ren MUAV Hardware und Software, Kommunikationstechniken f{\"u}r den notwendigen Informationsaustausch, Flugdynamik, Regelungstechnik, insbesondere f{\"u}r verteilte / kooperative Steuerungstechniken, Graphentheorie f{\"u}r Kommunikationstopologie Modellierung und Sensoren-Technologie wie Differential GPS (DGPS). F{\"u}r eine Flotte von Agenten, die in unmittelbarer N{\"a}he fliegen, ist eine genaue Positionsbestimmung zwingend n{\"o}tig um Kollisionen zu vermeiden und die Anforderungen f{\"u}r die meisten Missionen wie Georeferenzierung zu erf{\"u}llen. F{\"u}r solche Szenarien ist DGPS ein potenzieller Kandidat. Ein Teil der Forschung konzentriert sich daher auf die Entwicklung von DGPS Code. Eines der Module dieser Forschung war Hardware-Implementierung. Ein einfacher Test-Aufbau zur Realisierung von Basisfunktionalit{\"a}ten f{\"u}r Formationsflug von Quadrocoptern wurde am Lehrstuhl f{\"u}r Informationstechnik in der Luft- und Raumfahrt der Universit{\"a}t W{\"u}rzburg entwickelt. Diese Testumgebung kann nicht nur zur Pr{\"u}fung und Validierung von Algorithmen f{\"u}r Formationsflug in realer Umgebung genutzt werden, sondern dient auch zur Ausbildung von Studenten. Ein bereits vorhandener Pr{\"u}fstand f{\"u}r einzelne Quadrocopter wurde mit den notwendigen Kommunikation und verteilten Steuerung erweitert, um Algorithmen f{\"u}r Formationsfl{\"u}ge in drei Freiheitsgraden (Roll / Nick / Gier) zu testen. Diese Studie umfasst die Bereiche der Kommunikation, Steuerungstechnik und Embedded-System-Programmierung. Das Bluetooth-Protokoll wurde f{\"u}r die gegenseitige Kommunikation zwischen zwei Quadrocoptern verwendet. Eine einfache Technik der Proportional-Integral-Differential (PID) Steuerung in Kombination mit Kalman-Filter wurde genutzt. Die MATLAB Instrument Control Toolbox wurde f{\"u}r die Datenanzeige, die Analyse und das Plotten verwendet. Plots k{\"o}nnen in Echtzeit gezeichnet werden und empfangene Daten k{\"o}nnen auch in Form von Dateien zur sp{\"a}teren Verwendung und Analyse gespeichert werden. Das System wurde preisg{\"u}nstig, unter Ber{\"u}cksichtigung eines einfachen Aufbaus, entwickelt. Der vorgeschlagene Aufbau ist sehr flexibel und kann einfach an ver{\"a}nderte Anforderungen angepasst werden. Als verteiltes Steuerungsschema wurde ein zentralisierter, heterogener Formationsflug Positionsregler formuliert, der einen „explicit model following Linear Quadratic Regulator Proportional Integral (LQR PI)" Regler verwendet. Der Anf{\"u}hrer Quadrocopter ist ein stabiles Referenzmodell mit der gew{\"u}nschten Dynamik, deren Ausgang vollkommen von den beiden Wingmen Quadrocopter verfolgt wird. Der Anf{\"u}hrer selbst wird durch Pole Placement Steuerverfahren mit den gew{\"u}nschten Stabilit{\"a}tseigenschaften gesteuert, w{\"a}hrend die beiden Anh{\"a}nger durch robuste und adaptive LQR PI Steuerverfahren geregelt werden. F{\"u}r diese Studie wird ein Vollzustandsvektor der Quadrocopter betrachtet w{\"a}hrend nur die resultierende Leistung verfolgt wird. Die ausgew{\"a}hlte 3D Formationsgeometrie und die statische Stabilit{\"a}t bleibt unter einer Vielzahl von m{\"o}glichen St{\"o}rungen erhalten. Bei Kommunikationsverlust zwischen Anf{\"u}hrer und einem der Anh{\"a}nger, leitet der andere Anh{\"a}nger die Daten, die er vom Anf{\"u}hrer erhalten hat, an den betroffenen Anh{\"a}nger weiter. Die Stabilit{\"a}t des Regelsystems wurde unter Verwendung von Singul{\"a}rwerten analysiert. Der vorgeschlagene Ansatz f{\"u}r eng gekoppelten Formationsflug von MUAVs wurde mit Hilfe von umfangreichen Simulationen unter MATLAB® / Simulink® validiert und ergab viel versprechende Ergebnisse. Auch die Tracking-Leistung wurde f{\"u}r zeitlich ver{\"a}nderliche Befehle gezeigt. Die vorgeschlagene Architektur ist skalierbar und kann problemlos erweitert werden. Dieser Ansatz ist f{\"u}r die Szenarien geeignet, die eng gekoppelte Formationsflug ben{\"o}tigen, wie kooperatives Greifen oder gemeinsame Lasttransporte. Ein innovatives Framework f{\"u}r die Teamarbeit von zwei Quadrocopter Flotten wurde entwickelt. Als Beispielmission wurde ein Szenario gew{\"a}hlt, bei dem ein Feuer auf einer gr{\"o}ßeren Fl{\"a}che gel{\"o}scht werden muss. Jede Formation hat ihre angegebene Formationsgeometrie und eine zugewiesene Aufgabe. Die Lageregelung f{\"u}r die Quadrocopter in einer der Formationen wurde durch ein LQR PI-Regelschema, das auf „explicit model following" basiert, umgesetzt. Die Quadrocopter in anderen Formation werden durch ein LQR PI Servomechanismus Regelsystem gesteuert. Die beiden Steuersysteme werden in Bezug auf ihre Leistung und ihren Steuerungsaufwand verglichen. Beide Formationen werden durch entsprechende Bodenstationen durch virtuelle Anf{\"u}hrer kommandiert. Die Bodenstationen tauschen die befohlene H{\"o}heninformation aus, um gegenseitig eine sichere Trennung zwischen den Formationen zu gew{\"a}hrleisten. Die Quadrocopter k{\"o}nnen kommandierte Solltrajektorien folgen und {\"u}ber erw{\"u}nschten Punkten f{\"u}r eine vorgegebene Zeit schweben. Bei Kommunikationsverlust zwischen Bodenstation und einem der Quadcopter leitet der benachbarte Quadrocopter die Befehlsdaten, die er von der Bodenstation erhalten hat, an die betroffene Einheit weiter. Das vorgeschlagene Framework wurde durch umfangreiche Simulationen mit Hilfe von MATLAB® / Simulink® validiert und liefert sehr brauchbare Ergebnisse. Cluster-Rekonfiguration von Agenten wird in unserer Arbeit ebenfalls gezeigt. Dies erlaubt es die Formationsgeometrie w{\"a}hrend des Fluges auf eine beliebige neue Form umzuschalten. F{\"u}r die genannten Anwendungen sind Konsens Algorithmen nicht erw{\"u}nscht, da wir von den Quadrocopter Flotten fordern, dass sie dem von uns gew{\"a}hlten Weg folgen, und nicht ihren Weg selbst w{\"a}hlen. Eine Reihe der praktischen Probleme von Kommunikationsnetzen kann in geeigneter Weise durch Graphen dargestellt werden. Dies erleichtert die Problemformulierung und den Analyseprozess. Kommunikationstopologien f{\"u}r Netzwerke mit einer großen Anzahl von Einheiten, wie zum Beispiel Schw{\"a}rme von Luftfahrzeugen, k{\"o}nnen durch einen graphentheoretischen Ansatz untersucht werden. Um die Bildung solcher Probleme zu erleichtern, wird der Graph mit Hilfe der Laplace-Matrix dargestellt. Eigenwerte der Laplace-Matrix wurden in unserer Studie angemessene Ber{\"u}cksichtigung gegeben einen Einblick in die Graphen / Subgraphen Eigenschaften zu verleihen. Der gleiche wurden genutzt um die bekannte Euler Formel zu verallgemeinern und somit auf Graphen und Subgraphen anwendbar zu machen. Eine modifizierte Euler-Formel wird ebenfalls vorgestellt. Die Verwendung der Graphentheorie in verteilten / kooperativen Regelsystemen wird auch durch Simulationen gezeigt. Kooperative Kontrolschemas, die auf auf Konsens-Algorithmen beruhenden, wurden f{\"u}r die Lageregelung von Quadrocopter-Flotten, in denen kein expliziter Anf{\"u}hrer existiert, verwendet. Konsens-Algorithmen wurden in Kombination mit verschiedenen Steuersystemen verwendet, was zur Autonomie von Quadrocoptern beitr{\"a}gt. Die Steuersysteme, die f{\"u}r diesen Zweck verwendet werden, umfassen LQR PI-Regelung basierend auf „model following" und LQR PI Servo-Mechanismus. Die Regelungen wurden unter verschiedenen Kommunikationstopologien untersucht, darunter voll verbundene ungerichtete Graphen, gerichteten Graphen und Zyklus-Topologie. Der Informationsfluss unter den Agenten in einem Cluster wurde durch Laplace-Matrix modelliert. Die Auswirkungen von Eingangs Verzerrungen auf Konsens Werte wurden ebenfalls untersucht. Quadrocopter k{\"o}nnen durch gegenseitigen Konsens Flugbahnen verfolgen und die Zielpunkte erreichen. Die vorgeschlagenen Regelungssysteme wurden unter verschiedenen Kommunikationstopologien in Matlab / Simulink-Umgebung durch umfangreiche Simulationen validiert. Die Ergebnisse bescheinigen die Wirksamkeit der pr{\"a}sentierten Schemata mit dem zus{\"a}tzlichen Vorteil der Einfachheit der Umsetzung. Das vorgeschlagene Regelungssystem ist skalierbar f{\"u}r große Gruppen von MUAVs. F{\"u}r Formationsflug sind die Anforderungen an die Positionsgenauigkeit sehr hoch. GPS-Signale allein bieten keine ausreichend hohe Positionsgenauigkeit um die Anforderung zu erf{\"u}llen; eine Technik f{\"u}r die genauere Positionsbestimmung ist daher erforderlich, beispielsweise DGPS. Es existiert eine Anzahl von {\"o}ffentlichen Codes f{\"u}r die GPS-Positionsbestimmung und Baseline-Bestimmung im Offline-Modus. Es existiert jedoch keine Software f{\"u}r DGPS, die Korrekturfaktoren der Basisstationen nutzt, ohne auf Doppel Differenz Informationen zu vertrauen. Um dies zu erreichen, wurde eine Methodik in MATLAB-Umgebung f{\"u}r DGPS mit C/A Pseudoranges nur auf einzelne Frequenz L1 eingef{\"u}hrt es machbar f{\"u}r Empf{\"a}nger kosteng{\"u}nstig GPS zu nutzen. Unsere Basisstation wird an einem genau vermessen Referenzpunkt aufgestellt. Pseudoranges und geometrische Abst{\"a}nde werden an der Basisstation verglichen, um die Korrekturfaktoren zu berechnen. Diese Korrekturfaktoren, f{\"u}r aller g{\"u}ltigen Satelliten w{\"a}hrend einer Epoche, werden dann an einen Rover {\"u}bergeben. Das Rover ber{\"u}cksichtigt innerhalb der entsprechenden Epoche diese f{\"u}r seine eigene wahre Positionsbestimmung. Zur Validierung der vorgeschlagenen Algorithmen wird unsere Rover ebenfalls an einer vorbestimmten Stelle platziert. Der vorgeschlagene Code ist ein geeignetes und einfaches Werkzeug f{\"u}r die Nachbearbeitung von GPS-Rohdaten f{\"u}r eine genaue Positionsbestimmung eines Rover, z.B. eines UAV w{\"a}hrend der Post-Missionsanalyse.},
  subject      = {Micro Air Vehicle},
  language  = {en}
}
@article{AltieriSbieraDellaCasaetal.2017,
  author    = {Altieri, Barbara and Sbiera, Silviu and Della Casa, Silvia and Weigand, Isabel and Wild, Vanessa and Steinhauer, Sonja and Fadda, Guido and Kocot, Arkadius and Bekteshi, Michaela and Mambretti, Egle M. and Rosenwald, Andreas and Pontecorvi, Alfredo and Fassnacht, Martin and Ronchi, Cristina L.},
  title     = {Livin/BIRC7 expression as malignancy marker in adrenocortical tumors},
  series = {Oncotarget},
  volume    = {8},
  journal   = {Oncotarget},
  number    = {6},
  doi       = {10.18632/oncotarget.14067},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171887},
  pages     = {9323-9338},
  year      = {2017},
  abstract  = {Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R. The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression. Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform β more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability. In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.},
  language  = {en}
}
@article{AmorettiAreanArgurioetal.2017,
  author    = {Amoretti, Andrea and Are{\´a}n, Daniel and Argurio, Riccardo and Musso, Daniele and Zayas, Leopoldo A. Pando},
  title     = {A holographic perspective on phonons and pseudo-phonons},
  series = {Journal of High Energy Physics},
  volume    = {5},
  journal   = {Journal of High Energy Physics},
  number    = {51},
  doi       = {10.1007/JHEP05(2017)051},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170882},
  year      = {2017},
  abstract  = {We analyze the concomitant spontaneous breaking of translation and conformal symmetries by introducing in a CFT a complex scalar operator that acquires a spatially dependent expectation value. The model, inspired by the holographic Q-lattice, provides a privileged setup to study the emergence of phonons from a spontaneous translational symmetry breaking in a conformal field theory and offers valuable hints for the treatment of phonons in QFT at large. We first analyze the Ward identity structure by means of standard QFT techniques, considering both spontaneous and explicit symmetry breaking. Next, by implementing holographic renormalization, we show that the same set of Ward identities holds in the holographic Q-lattice. Eventually, relying on the holographic and QFT results, we study the correlators realizing the symmetry breaking pattern and how they encode information about the low-energy spectrum.},
  language  = {en}
}
@article{AmpattuHagmannLiangetal.2017,
  author    = {Ampattu, Biju Joseph and Hagmann, Laura and Liang, Chunguang and Dittrich, Marcus and Schl{\"u}ter, Andreas and Blom, Jochen and Krol, Elizaveta and Goesmann, Alexander and Becker, Anke and Dandekar, Thomas and M{\"u}ller, Tobias and Schoen, Christoph},
  title     = {Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence},
  series = {BMC Genomics},
  volume    = {18},
  journal   = {BMC Genomics},
  number    = {282},
  doi       = {10.1186/s12864-017-3616-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157534},
  year      = {2017},
  abstract  = {Background: Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence. Results: Despite indistinguishable ex vivo phenotypes, both strains differed in the expression of over 500 genes under infection mimicking conditions. These differences comprised in particular metabolic and information processing genes as well as genes known to be involved in host-damage such as the nitrite reductase and numerous LOS biosynthesis genes. A model based analysis of the transcriptomic differences in human blood suggested ensuing metabolic flux differences in energy, glutamine and cysteine metabolic pathways along with differences in the activation of the stringent response in both strains. In support of the computational findings, experimental analyses revealed differences in cysteine and glutamine auxotrophy in both strains as well as a strain and condition dependent essentiality of the (p)ppGpp synthetase gene relA and of a short non-coding AT-rich repeat element in its promoter region. Conclusions: Our data suggest that meningococcal virulence is linked to transcriptional buffering of cryptic genetic variation in metabolic genes including global stress responses. They further highlight the role of regulatory elements for bacterial virulence and the limitations of model strain approaches when studying such genetically diverse species as N. meningitidis.},
  language  = {en}
}
@article{ApostolidisGkarpousisKoch2017,
  author    = {Apostolidis -Gkarpousis, Alexandros and Koch, Christian},
  title     = {Convergences et divergences dans les articles «Langage» de Louis de Jaucourt et «Langue» de Nicolas Beauz{\´e}e. Une comparaison de deux articles de l'Encyclop{\´e}die de Diderot et D'Alembert},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {3},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2510-2613},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172843},
  pages     = {19-36},
  year      = {2017},
  abstract  = {The two articles of «Langage» and «Langue», published in 1765 in the 9th volume of the great French Encyclop{\´e}die by Diderot and D'Alembert, treat some essential philosophical questions on the human ability of communication with linguistic signs. Nevertheless, as the two authors Jaucourt and Beauz{\´e}e did not share completely identic points of view, the comparative lecture of both articles reveals a complementary perspective, particularly relating to the origin of language as a divine gift or humans' creation for communicative needs. A further aspect of divergence concerns the textual composition of the article « Langage » as a structured informative text, and the article « Langue » as a long and freely composed writing including personal remarks by the author. The following article deals with the potential of approaches to the Encyclop{\´e}die in modern linguistics, concretely demonstrated in the comparative analysis of these two articles.},
  language  = {fr}
}
@article{AppelSchulerVogeletal.2017,
  author    = {Appel, Patricia and Schuler, Michael and Vogel, Heiner and Oezelsel, Amina and Faller, Hermann},
  title     = {Short Questionnaire for Workplace Analysis (KFZA): factorial validation in physicians and nurses working in hospital settings},
  series = {Journal of Occupational Medicine and Toxicology},
  volume    = {12},
  journal   = {Journal of Occupational Medicine and Toxicology},
  number    = {11},
  doi       = {10.1186/s12995-017-0157-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157510},
  year      = {2017},
  abstract  = {Background: In recent years, there has been an increasing interest in psychosocial workplace risk assessments in Germany. One of the questionnaires commonly employed for this purpose is the Short Questionnaire for Workplace Analysis (KFZA). Originally, the KFZA was developed and validated for office workers. The aim of the present study was to examine the factorial validity of the KFZA when applied to hospital settings. Therefore, we examined the factorial structure of a questionnaire that contained all the original items plus an extension adding 11 questions specific to hospital workplaces and analyzed both, the original version and the extended version. Methods: We analyzed questionnaire data of a total of 1731 physicians and nurses obtained over a 10-year period. Listwise exclusion of data sets was applied to account for variations in questionnaire versions and yielded 1163 questionnaires (1095 for the extended version) remaining for factor analysis. To examine the factor structure, we conducted a principal component factor analysis. The number of factors was determined using the Kaiser criterion and scree-plot methods. Factor interpretation was based on orthogonal Varimax rotation as well as oblique rotation. Results: The Kaiser criterion revealed a 7-factor solution for the 26 items of the KFZA, accounting for 62.0\% of variance. The seven factors were named: "Social Relationships", "Job Control", "Opportunities for Participation and Professional Development", "Quantitative Work Demands", "Workplace Environment", "Variability" and "Qualitative Work Demands". The factor analysis of the 37 items of the extended version yielded a 9-factor solution. The two additional factors were named "Consequences of Strain" and "Emotional Demands". Cronbach's α ranged from 0.63 to 0.87 for these scales. Conclusions: Overall, the KFZA turned out to be applicable to hospital workers, and its content-related structure was replicated well with some limitations. However, instead of the 11 factors originally proposed for office workers, a 7-factor solution appeared to be more suitable when employed in hospitals. In particular, the items of the KFZA factor "Completeness of Task" might need adaptation for the use in hospitals. Our study contributes to the assessment of the validity of this popular instrument and should stimulate further psychometric testing.},
  language  = {en}
}
@article{AppeltMenzelCubukovaGuentheretal.2017,
  author    = {Appelt-Menzel, Antje and Cubukova, Alevtina and G{\"u}nther, Katharina and Edenhofer, Frank and Piontek, J{\"o}rg and Krause, Gerd and St{\"u}ber, Tanja and Walles, Heike and Neuhaus, Winfried and Metzger, Marco},
  title     = {Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells},
  series = {Stem Cell Reports},
  volume    = {8},
  journal   = {Stem Cell Reports},
  number    = {4},
  doi       = {10.1016/j.stemcr.2017.02.021},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170982},
  pages     = {894-906},
  year      = {2017},
  abstract  = {In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm\(^{2}\) and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies.},
  language  = {en}
}
@article{ArenasRoces2017,
  author    = {Arenas, Andr{\´e}s and Roces, Flavio},
  title     = {Avoidance of plants unsuitable for the symbiotic fungus in leaf-cutting ants: Learning can take place entirely at the colony dump},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0171388},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157559},
  pages     = {e0171388},
  year      = {2017},
  abstract  = {Plants initially accepted by foraging leaf-cutting ants are later avoided if they prove unsuitable for their symbiotic fungus. Plant avoidance is mediated by the waste produced in the fungus garden soon after the incorporation of the unsuitable leaves, as foragers can learn plant odors and cues from the damaged fungus that are both present in the recently produced waste particles. We asked whether avoidance learning of plants unsuitable for the symbiotic fungus can take place entirely at the colony dump. In order to investigate whether cues available in the waste chamber induce plant avoidance in na{\"i}ve subcolonies, we exchanged the waste produced by subcolonies fed either fungicide-treated privet leaves or untreated leaves and measured the acceptance of untreated privet leaves before and after the exchange of waste. Second, we evaluated whether foragers could perceive the avoidance cues directly at the dump by quantifying the visits of labeled foragers to the waste chamber. Finally, we asked whether foragers learn to specifically avoid untreated leaves of a plant after a confinement over 3 hours in the dump of subcolonies that were previously fed fungicide-treated leaves of that species. After the exchange of the waste chambers, workers from subcolonies that had access to waste from fungicide-treated privet leaves learned to avoid that plant. One-third of the labeled foragers visited the dump. Furthermore, na{\"i}ve foragers learned to avoid a specific, previously unsuitable plant if exposed solely to cues of the dump during confinement. We suggest that cues at the dump enable foragers to predict the unsuitable effects of plants even if they had never been experienced in the fungus garden.},
  language  = {en}
}
@article{ArmbrusterKriegWeissenbergeretal.2017,
  author    = {Armbruster, Nicole and Krieg, Jennifer and Weißenberger, Manuel and Scheller, Carsten and Steinert, Andre F.},
  title     = {Rescued Chondrogenesis of Mesenchymal Stem Cells under Interleukin 1 Challenge by Foamyviral Interleukin 1 Receptor Antagonist Gene Transfer},
  series = {Frontiers in Pharmacology},
  volume    = {8},
  journal   = {Frontiers in Pharmacology},
  number    = {255},
  doi       = {10.3389/fphar.2017.00255},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170919},
  year      = {2017},
  abstract  = {Background: Mesenchymal stem cells (MSCs) and their chondrogenic differentiation have been extensively investigated in vitro as MSCs provide an attractive source besides chondrocytes for cartilage repair therapies. Here we established prototype foamyviral vectors (FVV) that are derived from apathogenic parent viruses and are characterized by a broad host range and a favorable integration pattern into the cellular genome. As the inflammatory cytokine interleukin 1 beta (IL1β) is frequently present in diseased joints, the protective effects of FVV expressing the human interleukin 1 receptor antagonist protein (IL1RA) were studied in an established in vitro model (aggregate culture system) of chondrogenesis in the presence of IL1β. Materials and Methods: We generated different recombinant FVVs encoding enhanced green fluorescent protein (EGFP) or IL1RA and examined their transduction efficiencies and transgene expression profiles using different cell lines and human primary MSCs derived from bone marrow-aspirates. Transgene expression was evaluated by fluorescence microscopy (EGFP), flow cytometry (EGFP), and ELISA (IL1RA). For evaluation of the functionality of the IL1RA transgene to block the inhibitory effects of IL1β on chondrogenesis of primary MSCs and an immortalized MSC cell line (TERT4 cells), the cells were maintained following transduction as aggregate cultures in standard chondrogenic media in the presence or absence of IL1β. After 3 weeks of culture, pellets were harvested and analyzed by histology and immunohistochemistry for chondrogenic phenotypes. Results: The different FVV efficiently transduced cell lines as well as primary MSCs, thereby reaching high transgene expression levels in 6-well plates with levels of around 100 ng/ml IL1RA. MSC aggregate cultures which were maintained in chondrogenic media without IL1β supplementation revealed a chondrogenic phenotype by means of strong positive staining for collagen type II and matrix proteoglycan (Alcian blue). Addition of IL1β was inhibitory to chondrogenesis in untreated control pellets. In contrast, foamyviral mediated IL1RA expression rescued the chondrogenesis in pellets cultured in the presence of IL1β. Transduced MSC pellets reached thereby very high IL1RA transgene expression levels with a peak of 1087 ng/ml after day 7, followed by a decrease to 194 ng/ml after day 21, while IL1RA concentrations of controls were permanently below 200 pg/ml. Conclusion: Our results indicate that FVV are capable of efficient gene transfer to MSCs, while reaching IL1RA transgene expression levels, that were able to efficiently block the impacts of IL1β in vitro. FVV merit further investigation as a means to study the potential as a gene transfer tool for MSC based therapies for cartilage repair.},
  language  = {en}
}
@phdthesis{Arnaudov2017,
  author    = {Arnaudov, Theresa Irina},
  title     = {Anthocyane - Modulation oxidativen Stresses in vivo und in vitro},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152593},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Die menschliche Nahrung enth{\"a}lt antioxidative Stoffe, die den Menschen m{\"o}glicherweise vor oxidativem Stress und seinen Konsequenzen sch{\"u}tzen k{\"o}nnen. Im Fokus der vorliegenden Arbeit standen Anthocyane, die als vielversprechende antioxidative Pflanzenstoffe in unterschiedlichen Obst- und Gem{\"u}sesorten zu finden sind. Im ersten Teil der Arbeit wurden in einem HT-29-Zellkulturmodell die zwei wichtigsten Vertreter der Anthocyanidine, Delphinidin und Cyanidin, untersucht. Es galt zu pr{\"u}fen, ob beide Pflanzenstoffe in geringen Konzentrationen in humanen Zellen antioxidativ wirken und oxidativen Genomschaden verhindern k{\"o}nnen. Im Comet-Assay reduzierten sowohl Delphinidin (ab 3,2 µM) als auch Cyanidin (ab 1 µM) signifikant die durch 100 µM Wasserstoffperoxid induzierten DNA-Sch{\"a}den in den HT-29-Zellen. Im Comet-Assays mit FPG-Enzym wurde deutlich, dass eine Pr{\"a}inkubation mit Cyanidin wirksam die Oxidation der DNA-Basen verringert. Die Auswirkungen auf den Glutathionspiegel wurden mit Hilfe des Glutathion-Recycling-Assays nach Tietze untersucht. Die Pr{\"a}inkubation mit Cyanidin f{\"u}hrte hierbei zu keinen signifikanten Ver{\"a}nderungen. Um die Auswirkungen der Anthocyanidine auf die intrazellul{\"a}re ROS-Produktion zu beobachten, wurde der fluoreszierenden Farbstoffs DHE verwendet. Sowohl Delphinidin (10 und 15 µM) als auch Cyanidin (10 und 20 µM) senkten signifikant die durch 25 µM Antimycin A angeregte ROS-Produktion. Im zweiten Teil der Arbeit wurde ein anthocyanreicher roter Fruchtsaft in einer 10-w{\"o}chigen Interventionsstudie am Menschen getestet. Hieran nahmen sowohl 19 Fibromyalgiepatienten als auch 10 gesunde Probanden teil. Es sollte die Hypothese gepr{\"u}ft werden, dass die konzentrierte und andauernde Einnahme des Saftes messbar oxidative Stressparameter im Blut ver{\"a}ndert. Außerdem sollten m{\"o}gliche Unterschiede im oxidativen Stresslevel zwischen Patienten und gesunden Probanden aufgedeckt werden. Nach jeder Studienphase erfolgte eine Befragung nach klinischen Symptomen und die Abgabe einer Urin- und Blutprobe in der Schmerzambulanz der Uniklinik W{\"u}rzburg (2 Wochen Einwaschphase, 4 Wochen Fruchtsaftphase mit je 750 ml Saft t{\"a}glich, 4 Wochen Auswaschphase). Das ROS-Level wurde mit 2 Methoden in den mononukle{\"a}ren Blutzellen untersucht: In der photometrischen NBT-Messung konnten keine signifikanten Unterschiede zwischen den Gruppen oder Zeitpunkten beobachtet werden. Bei der durchflusszytometrischen Messung mit Hilfe des fluoreszierenden DCF-Farbstoffes lag das ROS-Level der Patientengruppe vor Fruchtsafteinnahme signifikant h{\"o}her als das der Kontrollgruppe. Zur Messung der antioxidativen Kapazit{\"a}t wurde die Eisen-Reduktionsf{\"a}higkeit (FRAP) im Plasma untersucht. In der Patientengruppe zeigte sich eine Steigerung der antioxidativen Kapazit{\"a}t nach Einnahme des Fruchtsaftes. Die Unterschiede zwischen den beiden Gruppen waren gering. Sowohl das Gesamtglutathion als auch die oxidierte und reduzierte Form wurden in den Erythrozyten der Probanden mit dem Glutathion-Recycling-Assay gemessen. Nach der Fruchtsafteinnahme stieg die Konzentration des Gesamtglutathions in der Patientengruppe an. Zusammenfassend konnte in dieser Arbeit gezeigt werden, dass Delphinidin und Cyanidin auch in geringen Konzentrationen (1µM - 20µM) einen antioxidativer Effekt in HT-29-Zellen haben und vor oxidativem DNA-Schaden sch{\"u}tzen k{\"o}nnen. Die Ergebnisse der Interventionsstudie unterschieden sich teilweise in den einzelnen Endpunkten. Es war nicht m{\"o}glich, den Fibromyalgiepatienten ein h{\"o}heres oxidatives Stresslevel nachzuweisen. Ein Grund f{\"u}r die geringeren Effekte des Fruchtsaftes k{\"o}nnte in der eher geringen Bioverf{\"u}gbarkeit der Anthocyane liegen. Außerdem k{\"o}nnte die Heterogenit{\"a}t der Fibromyalgieerkrankung genauso wie andere endogene oder exogene Faktoren wie etwa Alter oder Medikamenteneinnahme die teilweise großen interindividuellen Schwankungen der Messergebnisse hinsichtlich der oxidativen Stressparameter bedingen. Klinisch profitierten einige der Fibromyalgiepatienten von der Fruchtsafteinnahme insbesondere hinsichtlich der Reizdarmsymptomatik. Dieses Volksleiden k{\"o}nnte ein interessanter Ansatzpunkt f{\"u}r Folgeuntersuchungen mit einem anthocyanreichen Produkt sein.},
  subject      = {Oxidativer Stress},
  language  = {de}
}
@article{ArnholdtGilbertBlanketal.2017,
  author    = {Arnholdt, J{\"o}rg and Gilbert, Fabian and Blank, Marc and Papazoglou, Jannis and Rudert, Maximilian and N{\"o}th, Ulrich and Steinert, Andre F.},
  title     = {The Mayo conservative hip: complication analysis and management of the first 41 cases performed at a University level 1 department},
  series = {BMC Muskoskeletal Disorders},
  volume    = {18},
  journal   = {BMC Muskoskeletal Disorders},
  number    = {250},
  doi       = {10.1186/s12891-017-1613-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157812},
  year      = {2017},
  abstract  = {Background: To prevent bone loss in hip arthroplasty, several short stem systems have been developed, including the Mayo conservative hip system. While there is a plethora of data confirming inherent advantages of these systems, only little is known about potential complications, especially when surgeons start to use these systems. Methods: In this study, we present a retrospective analysis of the patients' outcome, complications and the complication management of the first 41 Mayo conservative hips performed in 37 patients. For this reason, functional scores, radiographic analyses, peri- and postoperative complications were assessed at an average follow-up of 35 months. Results: The overall HHS improved from 61.2 pre-operatively to 85.6 post-operatively. The German Extra Short Musculoskeletal Function Assessment Questionnaire (XSFMA-D) improved from 30.3 pre-operatively to 12.2 post-operatively. The most common complication was an intraoperative non-displaced fracture of the proximal femur observed in 5 cases (12.1\%). Diabetes, higher BMI and older ages were shown to be risk factors for these intra-operative periprosthetic fractures (p < 0.01). Radiographic analysis revealed a good offset reconstruction in all cases. Conclusion: In our series, a high complication rate with 12.1\% of non-displaced proximal femoral fractures was observed using the Mayo conservative hip. This may be attributed to the flat learning curve of the system or the inherent patient characteristics of the presented cohort."},
  language  = {en}
}
@unpublished{ArrowsmithBraunschweigStennett2017,
  author    = {Arrowsmith, Merle and Braunschweig, Holger and Stennett, Tom},
  title     = {Formation and Reactivity of Electron-Precise B-B Single and Multiple Bonds},
  series = {Angewandte Chemie, International Edition},
  volume    = {56},
  journal   = {Angewandte Chemie, International Edition},
  number    = {1},
  doi       = {10.1002/anie.201610072},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145631},
  pages     = {96-115},
  year      = {2017},
  abstract  = {Recent years have seen rapid advances in the chemistry of small molecules containing electron-precise boron-boron bonds. This review provides an overview of the latest methods for the controlled synthesis of B-B single and multiple bonds as well as the ever-expanding range of reactivity displayed by the latter.},
  language  = {en}
}
@unpublished{ArrowsmithBoehnkeBraunschweigetal.2017,
  author    = {Arrowsmith, Merle and B{\"o}hnke, Julian and Braunschweig, Holger and Celik, Mehmet Ali},
  title     = {Reactivity of a Dihydrodiborene with CO: Coordination, Insertion, Cleavage and Spontaneous Cyclic Alkyne Formation},
  series = {Angewandte Chemie, International Edition},
  journal   = {Angewandte Chemie, International Edition},
  doi       = {10.1002/anie.201707907},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153318},
  year      = {2017},
  abstract  = {Under a CO atmosphere the dihydrodiborene [(cAAC)HB=BH(cAAC)] underwent coordination of CO concomitant with reversible hydrogen migration from boron to the carbene carbon atom, as well as reversible CO insertion into the B=B bond. Heating of the CO-adduct resulted in two unusual cAAC ring-expansion products, one presenting a B=C bond to a six-membered 1,2-azaborinane-3-ylidene, the other an unprecedented nine-membered cyclic alkyne resulting from reductive cleavage of CO and spontaneous C≡C triple bond formation.},
  language  = {en}
}
@unpublished{ArrowsmithBoehnkeBraunschweigetal.2017,
  author    = {Arrowsmith, Merle and B{\"o}hnke, Julian and Braunschweig, Holger and Deißenberger, Andrea and Dewhurst, Rian and Ewing, William and H{\"o}rl, Christian and Mies, Jan and Muessig, Jonas},
  title     = {Simple Solution-Phase Syntheses of Tetrahalodiboranes(4) and their Labile Dimethylsulfide Adducts},
  series = {Chemical Communications},
  volume    = {53},
  journal   = {Chemical Communications},
  doi       = {10.1039/C7CC03148C},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149438},
  pages     = {8265-8267},
  year      = {2017},
  abstract  = {Convenient, solution-phase syntheses of tetrahalodiboranes(4) B\(_2\)F\(_4\), B\(_2\)Cl\(_4\) and B\(_2\)I\(_4\) are presented herein from common precursor B\(_2\)Br\(_4\). In addition, the dimethylsulfide adducts B\(_2\)Cl\(_4\)(SMe\(_2\))\(_2\) and B\(_2\)Br\(_4\)(SMe\(_2\))\(_2\) are conveniently prepared in one-step syntheses from the commercially-available starting material B\(_2\)(NMe\(_2\))\(_4\). The results provide simple access to the full range of tetrahalodiboranes(4) for the exploration of their untapped synthetic potential.},
  language  = {en}
}
@phdthesis{Aschenbrenner2017,
  author    = {Aschenbrenner, Doris},
  title     = {Human Robot Interaction Concepts for Human Supervisory Control and Telemaintenance Applications in an Industry 4.0 Environment},
  isbn      = {978-3-945459-18-8},
  doi       = {10.25972/OPUS-15052},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150520},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {While teleoperation of technical highly sophisticated systems has already been a wide field of research, especially for space and robotics applications, the automation industry has not yet benefited from its results. Besides the established fields of application, also production lines with industrial robots and the surrounding plant components are in need of being remotely accessible. This is especially critical for maintenance or if an unexpected problem cannot be solved by the local specialists. Special machine manufacturers, especially robotics companies, sell their technology worldwide. Some factories, for example in emerging economies, lack qualified personnel for repair and maintenance tasks. When a severe failure occurs, an expert of the manufacturer needs to fly there, which leads to long down times of the machine or even the whole production line. With the development of data networks, a huge part of those travels can be omitted, if appropriate teleoperation equipment is provided. This thesis describes the development of a telemaintenance system, which was established in an active production line for research purposes. The customer production site of Braun in Marktheidenfeld, a factory which belongs to Procter \& Gamble, consists of a six-axis cartesian industrial robot by KUKA Industries, a two-component injection molding system and an assembly unit. The plant produces plastic parts for electric toothbrushes. In the research projects "MainTelRob" and "Bayern.digital", during which this plant was utilised, the Zentrum f{\"u}r Telematik e.V. (ZfT) and its project partners develop novel technical approaches and procedures for modern telemaintenance. The term "telemaintenance" hereby refers to the integration of computer science and communication technologies into the maintenance strategy. It is particularly interesting for high-grade capital-intensive goods like industrial robots. Typical telemaintenance tasks are for example the analysis of a robot failure or difficult repair operations. The service department of KUKA Industries is responsible for the worldwide distributed customers who own more than one robot. Currently such tasks are offered via phone support and service staff which travels abroad. They want to expand their service activities on telemaintenance and struggle with the high demands of teleoperation especially regarding security infrastructure. In addition, the facility in Marktheidenfeld has to keep up with the high international standards of Procter \& Gamble and wants to minimize machine downtimes. Like 71.6 \% of all German companies, P\&G sees a huge potential for early information on their production system, but complains about the insufficient quality and the lack of currentness of data. The main research focus of this work lies on the human machine interface for all human tasks in a telemaintenance setup. This thesis provides own work in the use of a mobile device in context of maintenance, describes new tools on asynchronous remote analysis and puts all parts together in an integrated telemaintenance infrastructure. With the help of Augmented Reality, the user performance and satisfaction could be raised. A special regard is put upon the situation awareness of the remote expert realized by different camera viewpoints. In detail the work consists of: - Support of maintenance tasks with a mobile device - Development and evaluation of a context-aware inspection tool - Comparison of a new touch-based mobile robot programming device to the former teach pendant - Study on Augmented Reality support for repair tasks with a mobile device - Condition monitoring for a specific plant with industrial robot - Human computer interaction for remote analysis of a single plant cycle - A big data analysis tool for a multitude of cycles and similar plants - 3D process visualization for a specific plant cycle with additional virtual information - Network architecture in hardware, software and network infrastructure - Mobile device computer supported collaborative work for telemaintenance - Motor exchange telemaintenance example in running production environment - Augmented reality supported remote plant visualization for better situation awareness},
  subject      = {Fernwartung},
  language  = {en}
}
@article{AshrafYasrebiHertleinetal.2017,
  author    = {Ashraf, Kerolos and Yasrebi, Kaveh and Hertlein, Tobias and Ohlsen, Knut and Lalk, Michael and Hilgeroth, Andreas},
  title     = {Novel effective small-molecule antibacterials against \(Enterococcus\) strains},
  series = {Molecules},
  volume    = {22},
  journal   = {Molecules},
  number    = {12},
  doi       = {10.3390/molecules22122193},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172628},
  year      = {2017},
  abstract  = {\(Enterococcus\) species cause increasing numbers of infections in hospitals. They contribute to the increasing mortality rates, mostly in patients with comorbidities, who suffer from severe diseases. \(Enterococcus\) resistances against most antibiotics have been described, including novel antibiotics. Therefore, there is an ongoing demand for novel types of antibiotics that may overcome bacterial resistances. We discovered a novel class of antibiotics resulting from a simple one-pot reaction of indole and \(o\)-phthaldialdehyde. Differently substituted indolyl benzocarbazoles were yielded. Both the indole substitution and the positioning at the molecular scaffold influence the antibacterial activity towards the various strains of \(Enterococcus\) species with the highest relevance to nosocomial infections. Structure-activity relationships are discussed, and the first lead compounds were identified as also being effective in the case of a vancomycin resistance.},
  language  = {en}
}
@unpublished{AuerhammerArrowsmithBissingeretal.2017,
  author    = {Auerhammer, Dominic and Arrowsmith, Merle and Bissinger, Philipp and Braunschweig, Holger and Dellermann, Theresa and Kupfer, Thomas and Lenczyk, Carsten and Roy, Dipak and Sch{\"a}fer, Marius and Schneider, Christoph},
  title     = {Increasing the Reactivity of Diborenes: Derivatization of NHC- Supported Dithienyldiborenes with Electron-Donor Groups},
  series = {Chemistry, A European Journal},
  journal   = {Chemistry, A European Journal},
  doi       = {10.1002/chem.201704669},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155419},
  year      = {2017},
  abstract  = {A series of NHC-supported 1,2-dithienyldiborenes was synthesized from the corresponding (dihalo)thienylborane NHC precursors. NMR and UV-vis spectroscopic data, as well as X-ray crystallographic analyses, were used to assess the electronic and steric influences on the B=B double bond of various NHCs and electron-donating substituents on the thienyl ligands. Crystallographic data showed that the degree of coplanarity of the diborene core and thienyl groups is highly dependent on the sterics of the substituents. Furthermore, any increase in the electron- donating ability of the substituents resulted in the destabilization of the HOMO and greater instability of the resulting diborenes.},
  language  = {en}
}
@article{AuerhammerArrowsmithBraunschweigetal.2017,
  author    = {Auerhammer, Dominic and Arrowsmith, Merle and Braunschweig, Holger and Dewhurst, Rian D. and Jim{\´e}nez-Halla, J. Oscar C. and Kupfer, Thomas},
  title     = {Nucleophilic addition and substitution at coordinatively saturated boron by facile 1,2-hydrogen shuttling onto a carbene donor},
  series = {Chemical Science},
  volume    = {8},
  journal   = {Chemical Science},
  number    = {10},
  doi       = {10.1039/c7sc03193a},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170255},
  pages     = {7066-7071},
  year      = {2017},
  abstract  = {The reaction of [(cAAC\(^{Me}\))BH\(_{3}\)] (cAAC\(^{Me}\) = 1-(2,6-iPr\(_{2}\)C\(_{6}\)H\(_{3}\))-3,3,5,5-tetramethylpyrrolidin-2-ylidene) with a range of organolithium compounds led to the exclusive formation of the corresponding (dihydro)organoborates, Li\(^{+}\)[(cAAC\(^{Me}\)H)BH\(_{2}\)R]- (R = sp\(^{3}\)-, sp\(^{2}\)-, or sp-hybridised organic substituent), by migration of one boron-bound hydrogen atom to the adjacent carbene carbon of the cAAC ligand. A subsequent deprotonation/salt metathesis reaction with Me3SiCl or spontaneous LiH elimination yielded the neutral cAAC-supported mono(organo)boranes, [(cAAC\(^{Me}\)H)BH\(_{2}\)R]- (R]. Similarly the reaction of [cAAC\(^{Me}\))BH\(_{3}\)] with a neutral donor base L resulted in adduct formation by shuttling one boron-bound hydrogen to the cAAC ligand, to generate [(cAAC\(^{Me}\)H)BH\(_{2}\)L], either irreversibly (L = cAAC\(^{Me}\)) or reversibly (L = pyridine). Variable-temperature NMR data and DFT calculations on [(cAAC\(^{Me}\)H)BH\(_{2}\)(cAAC\(^{Me}\))] show that the hydrogen on the former carbene carbon atom exchanges rapidly with the boron-bound hydrides.},
  language  = {en}
}
@article{AwadOthmanStopper2017,
  author    = {Awad, Eman and Othman, Eman M. and Stopper, Helga},
  title     = {Effects of resveratrol, lovastatin and the mTOR-inhibitor RAD-001 on insulin-induced genomic damage in vitro},
  series = {Molecules},
  volume    = {22},
  journal   = {Molecules},
  number    = {12},
  doi       = {10.3390/molecules22122207},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159260},
  pages     = {2207},
  year      = {2017},
  abstract  = {Diabetes mellitus (DM) is one of the major current health problems due to lifestyle changes. Before diagnosis and in the early years of disease, insulin blood levels are elevated. However, insulin generates low levels of reactive oxygen species (ROS) which are integral to the regulation of a variety of intracellular signaling pathways, but excess levels of insulin may also lead to DNA oxidation and DNA damage. Three pharmaceutical compounds, resveratrol, lovastatin and the mTOR-inhibitor RAD-001, were investigated due to their known beneficial effects. They showed protective properties against genotoxic damage and significantly reduced ROS after in vitro treatment of cultured cells with insulin. Therefore, the selected pharmaceuticals may be attractive candidates to be considered for support of DM therapy.},
  language  = {en}
}
@phdthesis{Bach2017,
  author    = {Bach, Tobias},
  title     = {Electromechanical interactions in lithium-ion batteries: Aging effects and analytical use},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153325},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {In the first part of his work, the causes for the sudden degradation of useable capacity of lithium-ion cells have been studied by means of complementary methods such as computed tomography, Post-Mortem studies and electrochemical analyses. The results obtained point unanimously to heterogeneous aging as a key-factor for the sudden degradation of cell capacity, which in turn is triggered by differences in local compression. At high states of health, the capacity fade rate is moderate but some areas of the graphite electrode degrade faster than others. Still, the localized changes are hardly noticeable on cell level due to averaging effects. Lithium plating occurs first in unevenly compressed areas, creating patterns visible to the human eye. As lithium plating leads to rapid consumption of active lithium, a sudden drop in capacity is observed on cell level. Lithium plating appears to spread out from the initial areas over the whole graphite electrode, quickly consuming the remaining useful lithium and active graphite. It can be hypothesized that a self-amplifying circle of reciprocal acceleration of local lithium loss and material loss causes rapid local degradation. Battery cell designers can improve cycle life by homogeneous pressure distribution in the cell and using negative active materials that are resilient to elevated discharge potentials such as improved carbons or lithium titanate. Also, a sufficiently oversized negative electrode and suitable electrolyte additives can help to avoid lithium plating. When packs are designed, care must be taken not to exert local pressure on parts of cells and to avoid both very high and low states of charge. In the second part of this dissertation the resilience of cylindrical and pouchbag cells to shocks and different vibrations was investigated. Stresses inflicted by vibration and shock tests according to the widely recognized UN38.3 transport test were compared to a long-time test that exposed cells to a 186 days long ordeal of sine sweep vibrations with a profile based on real-world applications. All cells passed visual and electric inspection performed by TU M{\"u}nchen after the vibration tests. Only cylindrical cells subjected to long-term vibrations in axial direction showed an increase in impedance and a loss of capacity that could be recuperated in part. The detailed analyses presented in this thesis gave more details on the damages inflicted by vibrations and shocks and revealed drastic damages in some cases. In cylindrical cells, only movement in axial direction caused damage. Long term vibrations were found to be especially detrimental. No damage whatsoever could be detected for pouch cells, regardless of the test protocol and the direction of movement. The extreme resilience of pouchbag cells shows that the electrode stack of lithium-ion cells is resistant to vibrations, and that damages are caused by design imperfections that can be improved at low cost. The findings of this work, and the general state of research show that it is most crucial to control the lithiation and thus potential of the graphite electrode. In the last part of this work, a new, direct method for charge estimation based on changing transmission is presented. A correlation between transmission of short ultrasonic pulses and state of charge is found. This new technology allows direct measurement of the state of charge. The method is demonstrated for batteries with different positive active materials, showing its versatility. As the observed changes can be traced to the lithiation of graphite, it can be determined without a reference electrode. Already at this early stage of development, the found correlations allow estimation of state of charge. The present hysteresis in the signal height of the slow wave, which is unneglectable especially during discharging at higher currents, will be subject to further investigation. The observed effects can be explained by effects on different length scales. Biot's theory explains the second wave's slowness based on the active material particles size in the range of 0.01 mm and electrolyte-filled pores. Lithiation of graphite changes the porosity of the electrode and thereby the velocity and wavelength of the impulse. When the wavelength approaches the length scale of the layers, 0.1 mm, scattering effects dampen the transmitted signal. Finally, the wavelength of the pulse should be shorter than the transducers diameter to obtain a homogeneous wave front. To conclude, the new method allows the control of each individual cell in a pack independent from the electrical connections of the cells. As the method shows great promise, further studies regarding factors such as long-term behavior, temperature and current rates should be conducted. In this thesis hysteresis was observed and a deeper understanding of the reasons behind it may allow further improvements of measurement precision.},
  subject      = {Lithium-Ionen-Akkumulator},
  language  = {en}
}
@article{BailNotzRovitusoetal.2017,
  author    = {Bail, Kathrin and Notz, Quirin and Rovituso, Damiano M. and Schampel, Andrea and Wunsch, Marie and Koeniger, Tobias and Schropp, Verena and Bharti, Richa and Scholz, Claus-Juergen and Foerstner, Konrad U. and Kleinschnitz, Christoph and Kuerten, Stefanie},
  title     = {Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis.},
  series = {Journal of Neuroinflammation},
  volume    = {14},
  journal   = {Journal of Neuroinflammation},
  number    = {148},
  doi       = {10.1186/s12974-017-0924-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157869},
  year      = {2017},
  abstract  = {Background: MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS). Methods: MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P\(_{1}\) receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro. Results: FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220\(^{+}\) B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs. Conclusions: The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.},
  language  = {en}
}
@article{BalasubramanianOthmanKampiketal.2017,
  author    = {Balasubramanian, Srikkanth and Othman, Eman M. and Kampik, Daniel and Stopper, Helga and Hentschel, Ute and Ziebuhr, Wilma and Oelschlaeger, Tobias A. and Abdelmohsen, Usama R.},
  title     = {Marine sponge-derived Streptomyces sp SBT343 extract inhibits staphylococcal biofilm formation},
  series = {Frontiers in Microbiology},
  volume    = {8},
  journal   = {Frontiers in Microbiology},
  doi       = {10.3389/fmicb.2017.00236},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171844},
  year      = {2017},
  abstract  = {Staphylococcus epidermidis and Staphylococcus aureus are opportunistic pathogens that cause nosocomial and chronic biofilm-associated infections. Indwelling medical devices and contact lenses are ideal ecological niches for formation of staphylococcal biofilms. Bacteria within biofilms are known to display reduced susceptibilities to antimicrobials and are protected from the host immune system. High rates of acquired antibiotic resistances in staphylococci and other biofilm-forming bacteria further hamper treatment options and highlight the need for new anti-biofilm strategies. Here, we aimed to evaluate the potential of marine sponge-derived actinomycetes in inhibiting biofilm formation of several strains of S. epidermidis, S. aureus, and Pseudomonas aeruginosa. Results from in vitro biofilm-formation assays, as well as scanning electron and confocal microscopy, revealed that an organic extract derived from the marine sponge-associated bacterium Streptomyces sp. SBT343 significantly inhibited staphylococcal biofilm formation on polystyrene, glass and contact lens surfaces, without affecting bacterial growth. The extract also displayed similar antagonistic effects towards the biofilm formation of other S. epidermidis and S. aureus strains tested but had no inhibitory effects towards Pseudomonas biofilms. Interestingly the extract, at lower effective concentrations, did not exhibit cytotoxic effects on mouse fibroblast, macrophage and human corneal epithelial cell lines. Chemical analysis by High Resolution Fourier Transform Mass Spectrometry (HRMS) of the Streptomyces sp. SBT343 extract proportion revealed its chemical richness and complexity. Preliminary physico-chemical characterization of the extract highlighted the heat-stable and non-proteinaceous nature of the active component(s). The combined data suggest that the Streptomyces sp. SBT343 extract selectively inhibits staphylococcal biofilm formation without interfering with bacterial cell viability. Due to absence of cell toxicity, the extract might represent a good starting material to develop a future remedy to block staphylococcal biofilm formation on contact lenses and thereby to prevent intractable contact lens-mediated ocular infections.},
  language  = {en}
}
@article{BanksMillardBehnamianetal.2017,
  author    = {Banks, Sarah and Millard, Koreen and Behnamian, Amir and White, Lori and Ullmann, Tobias and Charbonneau, Francois and Chen, Zhaohua and Wang, Huili and Pasher, Jon and Duffe, Jason},
  title     = {Contributions of actual and simulated satellite SAR data for substrate type differentiation and shoreline mapping in the Canadian Arctic},
  series = {Remote Sensing},
  volume    = {9},
  journal   = {Remote Sensing},
  number    = {12},
  doi       = {10.3390/rs9121206},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172630},
  year      = {2017},
  abstract  = {Detailed information on the land cover types present and the horizontal position of the land-water interface is needed for sensitive coastal ecosystems throughout the Arctic, both to establish baselines against which the impacts of climate change can be assessed and to inform response operations in the event of environmental emergencies such as oil spills. Previous work has demonstrated potential for accurate classification via fusion of optical and SAR data, though what contribution either makes to model accuracy is not well established, nor is it clear what shorelines can be classified using optical or SAR data alone. In this research, we evaluate the relative value of quad pol RADARSAT-2 and Landsat 5 data for shoreline mapping by individually excluding both datasets from Random Forest models used to classify images acquired over Nunavut, Canada. In anticipation of the RADARSAT Constellation Mission (RCM), we also simulate and evaluate dual and compact polarimetric imagery for shoreline mapping. Results show that SAR data is needed for accurate discrimination of substrates as user's and producer's accuracies were 5-24\% higher for models constructed with quad pol RADARSAT-2 and DEM data than models constructed with Landsat 5 and DEM data. Models based on simulated RCM and DEM data achieved significantly lower overall accuracies (71-77\%) than models based on quad pol RADARSAT-2 and DEM data (80\%), with Wetland and Tundra being most adversely affected. When classified together with Landsat 5 and DEM data, however, model accuracy was less affected by the SAR data type, with multiple polarizations and modes achieving independent overall accuracies within a range acceptable for operational mapping, at 89-91\%. RCM is expected to contribute positively to ongoing efforts to monitor change and improve emergency preparedness throughout the Arctic.},
  language  = {en}
}
@phdthesis{Basali2017,
  author    = {Basali, Timo},
  title     = {Untersuchung der Nierensch{\"a}digung durch Aldosteron am Rattenmodell {\"u}ber die Quantifizierung von Sch{\"a}digungsmarkern mittels Real-Time PCR-Technik},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151311},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Die Breite der Wirkungen von Aldosteron auf Nierenzellen wurde lange Zeit untersch{\"a}tzt. Inzwischen zeigte sich ein nicht unerheblicher Anteil des Hyperaldosteronismus an arterieller Hypertonie und ebenso mehren sich die Hinweise auf damit assoziierter erh{\"o}hter Inzidenz f{\"u}r maligne Entartung von Nierengewebe. In dieser Arbeit wurde der Effekt von Hyperaldosteronismus auf Nierenzellen von Ratten in vivo untersucht. Mittels real time quantitative PCR wurden die relative Expressionsver{\"a}nderungen der mRNA von validierten Nierensch{\"a}digungsmarkern im Hyperaldosteronismusmodell kontrolliert beobachtet und statistisch ausgewertet. Anders als im analog durchgef{\"u}hrten Vorversuch mit DOCA an der Stelle von Aldosteron, ließ sich gr{\"o}ßtenteils kein {\"u}ber der nat{\"u}rlichen Streuung der Daten liegender, signifikanter Effekt der Nierensch{\"a}digung durch {\"u}berh{\"o}hte Aldosteronspiegel nachweisen. Hierf{\"u}r kommen vielf{\"a}ltige Gr{\"u}nde in Frage. Neben der technischen Variabilit{\"a}t, der Beschaffenheit der internen Kontrolle, potentiell vorhandenen Inhibitoren und der Qualit{\"a}t der mRNA, konnten eine Reihe von weiteren Gr{\"u}nden als Ursache f{\"u}r die Diskrepanz zu den Ergebnissen der mit DOCA behandelten Tiere ausgeschlossen werden. Neben der theoretischen M{\"o}glichkeit inter-methodischer Differenzen und sich daraus ergebender Variationen, sowie der noch weiter zu untersuchenden Rolle des Glukokortikoidrezeptors durch dessen variable gleichzeitige Aktivierung, ist die Interpretation im Sinne eines zu gering ausgepr{\"a}gten Sch{\"a}digungseffektes durch den Hyperaldosteronismus f{\"u}r den gew{\"a}hlten Stichprobenumfang naheliegend. Hiermit stimmt auch die Tatsache {\"u}berein, dass der Effekt der Behandlung mit Aldosteron im Vergleich zur Behandlung mit DOCA von vorne herein deutlich geringer ausfallend erwartet wurde.},
  subject      = {Aldosteron},
  language  = {de}
}
@phdthesis{Bauer2017,
  author    = {Bauer, Steffen},
  title     = {Kombinierte Versorgung osteoporotischer Kompressionsfrakturen mit dorsaler Instrumentierung und Ballonkyphoplastie des betroffenen Wirbelk{\"o}rpers - Vergleich von konventioneller offener und minimalinvasiver Operationstechnik},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153947},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {In dieser Studie wurden Daten zur minimalinvasiven dorsalen Versorgung instabiler Frakturen der thorakolumbalen Wirbels{\"a}ule in Kombination mit Kyphoplastie erhoben. Das Patientenkollektiv umfasst 64 Patienten, welche im Zeitraum von 6/2009 bis 5/2011 an 67 Frakturen versorgt wurden. Das Durchschnittsalter bei Operation betrug 71,3 ± 8,9 Jahre. Es wurden hierzu die mono- und bisegmentalen Grund-Deckplatten-Winkel pr{\"a}operativ, postoperativ sowie an drei Nachuntersuchungszeitpunkten (6w, 3-6m, >9m) bestimmt. Weiterhin wurden mittels der Visuellen-Analog-Skala die Beschwerden vor dem Unfall und unmittelbar vor der Operation retrospektiv erhoben. Das funktionelle Ergebnis wurde am dritten Nachuntersuchungszeitpunkt mittels der VAS-Pain und des VAS-Wirbels{\"a}ulenscores der Arbeitsgemeinschaft „Wirbels{\"a}ule" der DGU ermittelt. Außerdem wurde nach einer regelm{\"a}ßigen Schmerzmitteleinnahme zu den Zeitpunkten „vor dem Unfall", „direkt nach dem Unfall" und „zurzeit" gefragt. Es konnten in anderen Studien schon einige Vorteile der minimalinvasiven dorsalen Stabilisierung hinsichtlich eines geringeren Blutverlustes, eines geringeren Gewebetraumas mit weniger postoperativer Schmerzen, einer besseren postoperativen Muskelfunktion, eines besseren kosmetischen Ergebnisses, schnellerer Mobilisierung sowie geringeren operativen Komplikationen gezeigt werden. Bisher gibt es aber keine Langzeitdaten, welche die funktionellen Ergebnisse und die Wiederaufrichtung oder den Korrekturverlust einer minimalinvasiven dorsalen Instrumentierung mit zeitgleicher Kyphoplastie von traumatischen Frakturen der thorakalen und lumbalen Wirbels{\"a}ule beschreiben. Hierbei konnten zu einem offen operierten Vergleichskollektiv keine signifikanten Unterschiede bzgl. der Wiederaufrichtung (5.2 ± 5.2 Grad perkutan vs. 6.4 ± 3.3 Grad offen, GDW bisegmental ermittelt) und des Korrekturverlustes des Grund-Deckplatten-Winkels gefunden werden (5.2 ± 5.6 Grad perkutan vs. 6.1 ± 2.4 Grad offen bei 3. NU, GDW bisegmental ermittelt). Signifikante Unterschiede ergaben sich aber bei den funktionellen Ergebnissen (VAS-Wirbels{\"a}ulenscore der Arbeitsgemeinschaft „Wirbels{\"a}ule" der DGU) zugunsten des minimalinvasiv versorgten Kollektivs zum Zeitpunkt der dritten Nachuntersuchung.},
  subject      = {Wirbels{\"a}ulenverletzung},
  language  = {de}
}
@unpublished{BaumannWillaschekKertessSzlaninkaetal.2017,
  author    = {Baumann, Christoph and Willaschek, Christian and Kertess-Szlaninka, Tuende and Lang, Johanna and Buchhorn, Reiner},
  title     = {Implementing high energy liquid nutrition, omega-3 fatty acids and nutritional supplements for the treatment of anorexia nervosa},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150430},
  year      = {2017},
  abstract  = {Objective: To examine the effects of two different treatment approaches on the course of anorexia nervosa (AN) over time. Methods: The subjects were 27 hospitalized AN patients (mean age: 14.91 years; mean BMI: 14.58; mean height: 163.56) . In our retrospective analysis we compared weight gain in two groups. While one group was treated with a standard oral refeeding protocol (historical control) through January 2013 (N=16), the second group (highly standardized refeeding protocol) received a high energy liquid nutrition and nutritional supplements including omega-3 fatty acids (N=11). Results: On admission, the two groups were comparable in terms of height, weight, age and heart rate. At the end of our monitoring time frame of 25 days, weight gain was 121.4\% higher in the highly standardized refeeding protocol group than in the historical control group (66.5 ±52.4 vs 147.3 ±55.7 grams/day; t-Test p=0.004; CI95\%: 29.3-132.2). About 45\% of our patients stated they were vegetarians at admission. However, we could not identify a vegetarian diet as a statistically significant negative prognostic factor for weight gain. Discussion: The highly standardized refeeding protocol seems to be helpful in malnourished AN patients to improve weight gain without enhancing the risk of a refeeding syndrome. Because of an increasing energy turnover, caloric intake should be adjusted during refeeding.},
  subject      = {Anorexia nervosa},
  language  = {en}
}
@article{BaurBuentemeyerMegerleetal.2017,
  author    = {Baur, Johannes and B{\"u}ntemeyer, Tjark-Ole and Megerle, Felix and Deutschbein, Timo and Spitzweg, Christine and Quinkler, Marcus and Nawroth, Peter and Kroiss, Matthias and Germer, Christoph-Thomas and Fassnacht, Martin and Steger, Ulrich},
  title     = {Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study},
  series = {BMC Cancer},
  volume    = {17},
  journal   = {BMC Cancer},
  number    = {522},
  doi       = {10.1186/s12885-017-3506-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159409},
  year      = {2017},
  abstract  = {Background: Metastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15\%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC. Methods: A retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included. Results: Seventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8\%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival. Conclusions: Liver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome.},
  language  = {en}
}
@article{BaurMatheGesierichetal.2017,
  author    = {Baur, Johannes and Mathe, Katrin and Gesierich, Anja and Weyandt, Gerhard and Wiegering, Armin and Germer, Christoph-Thomas and Gasser, Martin and Pelz, J{\"o}rg O. W.},
  title     = {Morbidity and oncologic outcome after saphenous vein-sparing inguinal lymphadenectomy in melanoma patients},
  series = {World Journal of Surgical Oncology},
  volume    = {15},
  journal   = {World Journal of Surgical Oncology},
  number    = {99},
  doi       = {10.1186/s12957-017-1164-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157687},
  year      = {2017},
  abstract  = {Background: Inguinal lymph node dissection (LND) is a surgical procedure with a high morbidity rate. Variations in surgical procedure, such as sparing of the saphenous vein, have been proposed to reduce surgical morbidity. While sparing of the saphenous vein has shown promising results in earlier studies, data for this procedure in melanoma patients are rare. In this retrospective study, we report 10-year findings on the effects of saphenous vein-sparing LND on surgical morbidity and oncologic outcomes in melanoma patients. Methods: A retrospective analysis of melanoma patients receiving inguinal LND in our facility between 2003 and 2013 was performed. Patients were divided into two groups: the saphenous vein resection group and the vein sparing group. Surgical morbidity, including wound infection, lymphatic fistula, severe bleeding, neurological complications, and chronic lymphedema, as well as regional recurrence-free survival were investigated. Results: A total of 106 patients were included in this study; of these, the saphenous vein was spared in 41 patients (38.7\%). The rate of lymphatic fistula was 51.6 vs. 48.8\%, wound infection occurred in 31.3 vs. 24.4\%, and patients suffered from chronic lymphedema in 30.0 vs. 26.5\% in V. saphena magna resection vs. sparing group. Differences observed, however, were not significant. No difference in regional recurrence-free survival between the two study groups was detected. Conclusions: The results of our retrospective analysis could not confirm the promising results reported in earlier studies. Thus, sparing of the saphenous vein appears to be optional.},
  language  = {en}
}
@article{BecamWalterBurgertetal.2017,
  author    = {Becam, J{\´e}r{\^o}me and Walter, Tim and Burgert, Anne and Schlegel, Jan and Sauer, Markus and Seibel, J{\"u}rgen and Schubert-Unkmeir, Alexandra},
  title     = {Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-017-18071-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159367},
  pages     = {17627},
  year      = {2017},
  abstract  = {Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C\(_{6}\)-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω-azido-C\(_{6}\)-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω-azido-C\(_{6}\)-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae.},
  language  = {en}
}
@article{BeerJoschinskiSastreetal.2017,
  author    = {Beer, Katharina and Joschinski, Jens and Sastre, Alazne Arrazola and Krauss, Jochen and Helfrich-F{\"o}rster, Charlotte},
  title     = {A damping circadian clock drives weak oscillations in metabolism and locomotor activity of aphids (Acyrthosiphon pisum)},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  number    = {14906},
  doi       = {10.1038/s41598-017-15014-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170020},
  year      = {2017},
  abstract  = {Timing seasonal events, like reproduction or diapause, is crucial for the survival of many species. Global change causes phenologies worldwide to shift, which requires a mechanistic explanation of seasonal time measurement. Day length (photoperiod) is a reliable indicator of winter arrival, but it remains unclear how exactly species measure day length. A reference for time of day could be provided by a circadian clock, by an hourglass clock, or, as some newer models suggest, by a damped circadian clock. However, damping of clock outputs has so far been rarely observed. To study putative clock outputs of Acyrthosiphon pisum aphids, we raised individual nymphs on coloured artificial diet, and measured rhythms in metabolic activity in light-dark illumination cycles of 16:08 hours (LD) and constant conditions (DD). In addition, we kept individuals in a novel monitoring setup and measured locomotor activity. We found that A. pisum is day-active in LD, potentially with a bimodal distribution. In constant darkness rhythmicity of locomotor behaviour persisted in some individuals, but patterns were mostly complex with several predominant periods. Metabolic activity, on the other hand, damped quickly. A damped circadian clock, potentially driven by multiple oscillator populations, is the most likely explanation of our results.},
  language  = {en}
}
@phdthesis{Beinicke2017,
  author    = {Beinicke, Andrea},
  title     = {Career Construction Across the Life Span: Career Choice and Career Development},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117447},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {This dissertation contributes to deepen our understanding of constructs that play a key role in individuals' vocational career construction. In this regard, many previous studies have focused exclusively on a specific phase of an individual's career. Yet, modern societies require continuous investments in one's career to adapt to changing Environments throughout the life span. Consequently, this dissertation takes a broad approach to capture a wide spectrum of career construction processes. According to Super's (1990) developmental stage framework, individuals have to manage vocational developmental tasks corresponding to each of the developmental life stages in order to be career mature across the life span. As the two stages exploration and maintenance set the stage for individuals' future career pathways, they are especially important in individuals' vocational career construction. Therefore, both of them are addressed in this dissertation. By answering open research questions relevant to career choice in early career stages and to career development in later career stages, this dissertation contributes to the overarching goal of shedding more light on constructs relevant to individuals' vocational career construction processes across the life span. Beyond the results presented within each study's horizon, this dissertation aimed at offering practical guidance to career counselors, trainees, and training and development (T\&D) professionals. Career counselors and T\&D professionals are involved in guiding vocational career construction processes of individuals across the life span. Thus, on the one hand, this dissertation supports career counselors' work so that they can help deliberating individuals make optimal and effective career choices. On the other hand, this dissertation facilitates T\&D professionals' work so that they can effectively design and evaluate e-learning and classroom trainings in corporate educational settings. Identifying individuals' vocational interests combined with cognitive abilities through adequate test measures and maximizing success of learning and success of transfer through fostering evidence-based transfer support actions will help individuals adapt quickly to the changing nature of work environments in the 21st century and to continue to successfully construct careers across the life span.},
  subject      = {Karriere},
  language  = {en}
}
@article{BellingerAltenmuellerVolkmann2017,
  author    = {Bellinger, Daniel and Altenm{\"u}ller, Eckart and Volkmann, Jens},
  title     = {Perception of time in music in patients with Parkinson's disease - The processing of musical syntax compensates for rhythmic deficits},
  series = {Frontiers in Neuroscience},
  volume    = {11},
  journal   = {Frontiers in Neuroscience},
  doi       = {10.3389/fnins.2017.00068},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171805},
  year      = {2017},
  abstract  = {Objective: Perception of time as well as rhythm in musical structures rely on complex brain mechanisms and require an extended network of multiple neural sources. They are therefore sensitive to impairment. Several psychophysical studies have shown that patients with Parkinson's disease (PD) have deficits in perceiving time and rhythms due to a malfunction of the basal ganglia (BG) network. Method: In this study we investigated the time perception of PD patients during music perception by assessing their just noticeable difference (JND) in the time perception of a complex musical Gestalt. We applied a temporal discrimination task using a short melody with a clear beat-based rhythm. Among the subjects, 26 patients under L-Dopa administration and 21 age-matched controls had to detect an artificially delayed time interval in the range between 80 and 300 ms in the middle of the musical period. We analyzed the data by (a) calculating the detection threshold directly, (b) by extrapolating the JNDs, (c) relating it to musical expertise. Results: Patients differed from controls in the detection of time-intervals between 220 and 300 ms (*p = 0.0200, n = 47). Furthermore, this deficit depended on the severity of the disease (*p = 0.0452; n = 47). Surprisingly, PD patients did not show any deficit of their JND compared to healthy controls, although the results showed a trend (*p = 0.0565, n = 40). Furthermore, no significant difference of the JND was found according to the severity of the disease. Additionally, musically trained persons seemed to have lower thresholds in detecting deviations in time and syntactic structures of music (*p = 0.0343, n = 39). Conclusion: As an explanation of these results, we would like to propose the hypothesis of a time-syntax-congruency in music perception suggesting that processing of time and rhythm is a Gestalt process and that cortical areas involved in processing of musical syntax may compensate for impaired BG circuits that are responsible for time processing and rhythm perception. This mechanism may emerge more strongly as the deficits in time processing and rhythm perception progress. Furthermore, we presume that top-down-bottom-up-processes interfere additionally and interact in this context of compensation.},
  language  = {en}
}
@article{BenderRothJob2017,
  author    = {Bender, Oliver and Roth, Charlotte E. and Job, Hubert},
  title     = {Protected areas and population development in the alps},
  series = {eco.mont : Journal on Protected Mountain Areas Research and Management},
  volume    = {9},
  journal   = {eco.mont : Journal on Protected Mountain Areas Research and Management},
  number    = {Special issue},
  doi       = {10.1553/eco.mont-9-sis5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181901},
  year      = {2017},
  abstract  = {Nearly a quarter of the Alpine area is covered by a dense network of large protected areas (LPAs) of the four categories national park(NP), biosphere reserve (BR), nature park and world natural heritage site (WNHS). From the time of early industrialization, the Alpine area has undergone a mixed and increasingly polarized demographic development between the poles of immigration and emigration. This article investigates the possible mutual impact of population development and the existence of LPAs. The research design includes a quantitative survey of all Alpine LPAs in terms of their population development and the structure of immigration in the first decade of the 21st century. This will be linked with qualitative expert interviews in four selected NPs. The overall results allow an interpretation of the statistical correlations between type of LPA and migration.},
  language  = {en}
}
@article{BenhalevyGuptaDananetal.2017,
  author    = {Benhalevy, Daniel and Gupta, Sanjay K. and Danan, Charles H. and Ghosal, Suman and Sun, Hong-Wei and Kazemeier, Hinke G. and Paeschke, Katrin and Hafner, Markus and Juranek, Stefan A.},
  title     = {The Human CCHC-type Zinc Finger Nucleic Acid-Binding Protein Binds G-Rich Elements in Target mRNA Coding Sequences and Promotes Translation},
  series = {Cell Reports},
  volume    = {18},
  journal   = {Cell Reports},
  number    = {12},
  doi       = {10.1016/j.celrep.2017.02.080},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171122},
  pages     = {2979-2990},
  year      = {2017},
  abstract  = {The CCHC-type zinc finger nucleic acid-binding protein (CNBP/ZNF9) is conserved in eukaryotes and is essential for embryonic development in mammals. It has been implicated in transcriptional, as well as post-transcriptional, gene regulation; however, its nucleic acid ligands and molecular function remain elusive. Here, we use multiple systems-wide approaches to identify CNBP targets and function. We used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify 8,420 CNBP binding sites on 4,178 mRNAs. CNBP preferentially bound G-rich elements in the target mRNA coding sequences, most of which were previously found to form G-quadruplex and other stable structures in vitro. Functional analyses, including RNA sequencing, ribosome profiling, and quantitative mass spectrometry, revealed that CNBP binding did not influence target mRNA abundance but rather increased their translational efficiency. Considering that CNBP binding prevented G-quadruplex structure formation in vitro, we hypothesize that CNBP is supporting translation by resolving stable structures on mRNAs.},
  language  = {en}
}
@article{BeningHamoudaOezkuretal.2017,
  author    = {Bening, Constanze and Hamouda, Khaled and Oezkur, Mehmet and Schimmer, Christoph and Schade, Ina and Gorski, Armin and Aleksic, Ivan and Leyh, Rainer},
  title     = {Rapid deployment valve system shortens operative times for aortic valve replacement through right anterior minithoracotomy},
  series = {Journal of Cardiothoracic Surgery},
  volume    = {12},
  journal   = {Journal of Cardiothoracic Surgery},
  number    = {27},
  doi       = {10.1186/s13019-017-0598-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159439},
  year      = {2017},
  abstract  = {Background: There is growing evidence from the literature that right anterior minithoracotomy aortic valve replacement (RAT-AVR) improves clinical outcome. However, increased cross clamp time is the strongest argument for surgeons not performing RAT-AVR. Rapid deployment aortic valve systems have the potential to decrease cross-clamp time and ease this procedure. We assessed clinical outcome of rapid deployment and conventional valves through RAT. Methods: Sixty-eight patients (mean age 76 ± 6 years, 32\% females) underwent RAT-AVR between 9/2013 and 7/2015. According to the valve type implanted the patients were divided into two groups. In 43 patients (R-group; mean age 74.1 ± 6.6 years) a rapid deployment valve system (Edwards Intuity, Edwards Lifesciences Corp; Irvine, Calif) and in 25 patients (C-group; mean age 74.2 ± 6.6 years) a conventional stented biological aortic valve was implanted. Results: Aortic cross-clamp (42.1 ± 12 min vs. 68.3 ± 20.3 min; p < 0.001) and bypass time (80.4 ± 39.3 min vs. 106.6 ± 23.2 min; p = 0.001) were shorter in the rapid deployment group (R-group). We observed no differences in clinical outcome. Postoperative gradients (R-group: max gradient, 14.3 ± 8 mmHg vs. 15.5 ± 5 mmHg (C-group), mean gradient, 9.2 ± 1.7 mmHg (R-group) vs. 9.1 ± 2.3 mmHg (C-group) revealed no differences. However, larger prostheses were implanted in C-group (25 mm; IQR 23-27 mm vs. 23 mm; IQR 21-25; p = 0.009). Conclusions: Our data suggest that the rapid deployment aortic valve system reduced cross clamp and bypass time in patients undergoing RAT-AVR with similar hemodynamics as with larger size stented prosthesis. However, larger studies and long-term follow-up are mandatory to confirm our findings.},
  language  = {en}
}
@phdthesis{Benkert2017,
  author    = {Benkert, Andreas},
  title     = {Soft x-ray spectroscopic study of methanol and glycine peptides in different physical environments},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147111},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Ionenspezifische Effekte treten in einer Vielzahl von w{\"a}ssrigen L{\"o}sungen aus Elektrolyten und gr{\"o}ßeren Molek{\"u}len wie Peptiden auf. Die Ionen bewirken dabei {\"A}nderungen in Eigenschaften wie z.B. der Viskosit{\"a}t, den Aktivit{\"a}ten von Enzymen, der Stabilit{\"a}t von Proteinen und deren Ein- bzw. Aussalzverhalten. Typischerweise wird die ionenabh{\"a}ngige Auspr{\"a}gung derartiger Effekte mithilfe der Hofmeister-Serie beschrieben, die urspr{\"u}nglich Ionen nach ihrer F{\"a}higkeit ordnete, die L{\"o}slichkeit von H{\"u}hnereiweis in Wasser zu steigern oder zu unterdr{\"u}cken. Die empirische Abfolge der Ionen in der Hofmeister-Serie kann jedoch bis heute nicht zweifelsfrei erkl{\"a}rt werden. Trotz weitreichender Bem{\"u}hungen, ein molekulares Verst{\"a}ndnis dieses Ph{\"a}nomens zu schaffen, konnte bisher keine Einigung {\"u}ber die zugrundeliegenden Mechanismen und die genauere Bestimmung und Lokalisierung der Wechselwirkung erzielt werden. Die resonante inelastische Weichr{\"o}ntgenstreuung (RIXS) kombiniert die beiden Methoden der R{\"o}ntgenemissions- (XES) und R{\"o}ntgenabsorptionsspektroskopie (XAS). So k{\"o}nnen mit RIXS Informationen sowohl {\"u}ber die besetzten als auch die unbesetzten elektronischen Zust{\"a}nde gesammelt und zu einem umfassenden Bild der elektronischen Struktur des Systems verkn{\"u}pft werden, was diese Methode zu einem vielversprechenden Werkzeug macht, etwas mehr Licht auf die Thematik zu werfen. Die in dieser Arbeit pr{\"a}sentierten Ergebnisse zielen deshalb darauf ab, ein verbessertes Verst{\"a}ndnis der Wechselwirkungen zwischen Salzen und Peptiden in w{\"a}ssriger L{\"o}sung zu schaffen. Hierf{\"u}r wird systematisch der Einfluss verschiedenster physikalischer Umgebungen auf die elektronische Struktur von kleinen Molek{\"u}len (Methanol und von Glycin abgeleitete Peptide) mittels Weichr{\"o}ntgenspektroskopie, unterst{\"u}tzt durch Dichtefunktionaltheorie (DFT) Rechnungen, untersucht. In einem ersten Schritt werden isolierte Molek{\"u}le ohne jeglicheWechselwirkung zu ihrer unmittelbaren Umgebung anhand von Methanol in der Gasphase als Modelsystem untersucht. Hierbei wird insbesondere der lokale und elementspezifische Charakter von RIXS demonstriert und die lokale elektronische Struktur von Methanols Hydroxyl- und Methylgruppe untersucht. Mithilfe von DFT-Rechnungen werden die beobachteten Emissionslinien in den XES-Spektren der Emission bestimmter Molek{\"u}lorbitale zugeordnet und deren relative Emissionsintensit{\"a}ten erl{\"a}utert. F{\"u}r eine resonante Anregung der ersten Resonanz an der Sauerstoff-K-Absorptionskante werden starke Isotopeneffekte beobachtet, die durch dynamische Prozesse an der Hydroxylgruppe erkl{\"a}rt werden k{\"o}nnen. Dies dient als hervorragendes Beispiel f{\"u}r m{\"o}gliche Auswirkungen, die eine lokale {\"A}nderung in der Geometrie oder Symmetrie des Molek{\"u}ls auf dessen elektronische Struktur haben kann. Im weiteren Verlauf dieser Arbeit wird das untersuchte Probensystem um die Aminos{\"a}ure Glycin und deren kleinste Peptide Diglycin und Triglycin, vorerst in ihrer kristallinen Form als Festk{\"o}rper, erweitert. Mithilfe von RIXS-Karten der Stickstoff- und Sauerstoff-K-Absorptionskanten wird erneut, unterst{\"u}tzt durch DFT-Rechnungen, ein umfassendes Bild der elektronischen Struktur der Molek{\"u}le gezeichnet. {\"A}hnlich zum Fall von Methanol werden die Emissionsspektren an der Stickstoff-K-Kante stark von dynamischen Prozessen an der protonierten Aminogruppe der Molek{\"u}le beeinflusst. Zudem wird gezeigt, dass RIXS gezielt dazu verwendet werden kann, das Stickstoffatom in der Peptidbindung anzuregen und die elektronische Struktur in dessen lokaler Umgebung zu untersuchen. Desweiteren wird ein einfaches Baukastenprinzip f{\"u}r XES-Spektren dazu genutzt, die spektralen Anteile der Emission aus {\"U}berg{\"a}ngen an den beiden Stickstoffatomen in Diglycin zu isolieren. In w{\"a}ssriger L{\"o}sung kann eine leichte Ver{\"a}nderung der elektronischen Struktur der Molek{\"u}le durch die Wechselwirkung mit benachbarten Wassermolek{\"u}len, vermutlich an den geladenen funktionellen Gruppen, beobachtet werden. Die Auswirkungen auf die XES-Spektren sind jedoch eher gering. Deutlich gr{\"o}ßere Ver{\"a}nderungen werden beobachtet, wenn man den Protonierungszustand der Molek{\"u}le {\"u}ber den pH-Wert der L{\"o}sung manipuliert. Sowohl die Protonierung der Carboxylgruppe f{\"u}r kleine pH-Werte als auch die Deprotonierung der Aminogruppe in basischer L{\"o}sung f{\"u}hren zu starken Ver{\"a}nderungen in den RIXS-Karten. In einer umfangreichen Untersuchung der XES-Spektren von Glycin als Funktion des pH-Wertes wird gezeigt, dass sich die {\"A}nderungen jedoch nicht nur {\"o}rtlich begrenzt auf die Umgebung der manipulierten funktionellen Gruppe, sondern auch auf die elektronische Struktur in weiter entfernten Bereichen des Molek{\"u}ls auswirken. Als Beispiel f{\"u}r Systeme in denen Hofmeister-Effekte beobachtet werden, werden zu guter Letzt gemischte w{\"a}ssrige L{\"o}sungen aus Diglycin und verschiedenen Salzen untersucht. Um den Einfluss verschiedener Kationen auf die elektronische Struktur der Diglycin Molek{\"u}le zu erfassen wird eine Reihe unterschiedlicher Chloride verwendet, wohingegen eine Reihe von Kaliumsalzen f{\"u}r die Untersuchung verschiedener Anionen herangezogen wird. In beiden F{\"a}llen werden ionenspezifische Auswirkungen auf die XES-Spektren von Diglycin beobachtet, die qualitativ der Sortierung innerhalb der Hofmeister-Serie folgen. Die beobachteten {\"A}nderungen deuten dabei darauf hin, dass Kationen unterschiedlich stark mit dem Sauerstoff in der Peptidbindung und dessen unmittelbarer Umgebung wechselwirken, wohingegen Anionen eine gesteigerte Affinit{\"a}t zur Aminogruppe von Diglycin aufweisen.},
  subject      = {Methanol},
  language  = {en}
}
@phdthesis{Bergauer2017,
  author    = {Bergauer, Lisa},
  title     = {Die Bedeutung des neurotrophen Faktors Glial cell line-derived neurotrophic factor (GDNF) f{\"u}r die Integrit{\"a}t der intestinalen Epithelbarriere},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155259},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {In der vorliegenden Arbeit wurden die Effekte des neurotrophen Faktors GDNF auf die Struktur und Funktion der intestinalen Epithelbarriere untersucht. Zellkulturen mit Caco2 beziehungsweise HT29B6 dienten als Modellsysteme f{\"u}r die Epithelschicht der Darmschleimhaut. Transwellsassays und TER-Messungen mittels ECIS-Ger{\"a}t fungierten als zentrale Untersuchungsmethoden zur Evaluation der funktionellen Barriereeigenschaft der Zellmonolayer. Die morphologischen und quantitativen Ver{\"a}nderungen von Zelljunktionsproteinen wurden mittels indirekter Immunfluoreszenzf{\"a}rbungen beziehungsweise Western Blot-Untersuchungen dargestellt. Um Migration- und Proliferationsverhalten nach Verletzung des Zellmonolayers zu untersuchen, f{\"u}hrten wir in vitro-Scratch-Assays durch. Zun{\"a}chst wurde best{\"a}tigt, dass intestinale Epithelzellen die GDNF-Rezeptoren GFRα1, GFRα2 und RET exprimieren. Es zeigte sich sowohl in Immunf{\"a}rbungen gegen Junktionsproteine als auch in Permeabilit{\"a}tsmessungen, dass GDNF zu einer verst{\"a}rkten Differenzierung der intestinalen Epithelbarriere f{\"u}hrt. In Inhibitions- und Aktivierungsexperimenten mit verschiedenen Mediatoren wurde als zugrunde liegender Mechanismus die Inaktiverung der p38 MAPK durch GDNF identifiziert. Weiterhin zeigten Versuche mit epithelialen Wundheilungsassays, dass GDNF, {\"u}ber eine cAMP/PKA-abh{\"a}ngige Induktion der Proliferation, zu einer Verbesserung der Wundheilung f{\"u}hrt. In Immunf{\"a}rbungen und Western Blot-Analysen wurde beobachtet, dass auch intestinale Epithelzelllinien in der Lage sind GDNF zu synthetisieren. Zusammenfassend konnte in der vorliegenden Arbeit erstmals gezeigt werden, dass der neurotrophe Faktor GDNF direkt auf die Differenzierung und Proliferation von kultivierten Enterozyten Einfluss nehmen kann. Die Tatsache, dass intestinale Epithelzellen selbst GDNF synthetisieren und sezernieren k{\"o}nnen, weist auf einen neuen autokrinen- oder parakrinen Wirkmechanismus des neurotrophen Faktors hin.},
  subject      = {Epithel},
  language  = {de}
}
@article{BergfeldDasariWerneretal.2017,
  author    = {Bergfeld, Arne and Dasari, Prasad and Werner, Sandra and Hughes, Timothy R. and Song, Wen-Chao and Hortschansky, Peter and Brakhage, Axel A. and H{\"u}nig, Thomas and Zipfel, Peter F. and Beyersdorf, Niklas},
  title     = {Direct binding of the pH-regulated Protein 1 (Pra1) from Candida albicans inhibits cytokine secretion by mouse CD4\(^{+}\) T cells},
  series = {Frontiers in Microbiology},
  volume    = {8},
  journal   = {Frontiers in Microbiology},
  number    = {844},
  doi       = {10.3389/fmicb.2017.00844},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158274},
  year      = {2017},
  abstract  = {Opportunistic infections with the saprophytic yeast Candida albicans are a major cause of morbidity in immunocompromised patients. While the interaction of cells and molecules of innate immunity with C. albicans has been studied to great depth, comparatively little is known about the modulation of adaptive immunity by C. albicans. In particular, direct interaction of proteins secreted by C. albicans with CD4\(^{+}\) T cells has not been studied in detail. In a first screening approach, we identified the pH-regulated antigen 1 (Pra1) as a molecule capable of directly binding to mouse CD4\(^{+}\) T cells in vitro. Binding of Pra1 to the T cell surface was enhanced by extracellular Zn\(^{2+}\) ions which Pra1 is known to scavenge from the host in order to supply the fungus with Zn\(^{2+}\). In vitro stimulation assays using highly purified mouse CD4\(^{+}\) T cells showed that Pra1 increased proliferation of CD4\(^{+}\) T cells in the presence of plate-bound anti-CD3 monoclonal antibody. In contrast, secretion of effector cytokines such as IFNγ and TNF by CD4\(^{+}\) T cells upon anti-CD3/ anti-CD28 mAb as well as cognate antigen stimulation was reduced in the presence of Pra1. By secreting Pra1 C. albicans, thus, directly modulates and partially controls CD4\(^{+}\) T cell responses as shown in our in vitro assays.},
  language  = {en}
}
@phdthesis{Berlin2017,
  author    = {Berlin, Christopher},
  title     = {Die Untersuchung der kardialen Folgen einer ubiquit{\"a}ren Deletion von RKIP in M{\"a}usen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152882},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Die Herzinsuffizienz, eine der h{\"a}ufigsten chronischen Krankheiten in der westlichen Welt, ist als Folge einer Myokardsch{\"a}digung durch eine verschlechterte Pumpfunktion des Herzens charakterisiert, die der K{\"o}rper durch verschiedene Kompensationsmechanismen zur Kontraktilit{\"a}tssteigerung auszugleichen versucht. Wichtiger Mechanismus hierf{\"u}r ist die Kontraktilit{\"a}ts- und Frequenzsteigerung {\"u}ber ß-adrenerge Rezeptorsignale, welche bei langfristiger Stimulation allerdings zu einer Abnahme der Funktionalit{\"a}t und Minderexpression eben dieses Rezeptorsystems, sowie der gleichzeitigen Verschlechterung der Herzinsuffizienz f{\"u}hrt. Interessanterweise wird parallel zur verminderten Rezeptorexpression bei Herzinsuffizienzpatienten eine Zunahme der GRK-Aktivit{\"a}t beobachtet. Diese Kinase ist in der Lage, ß-adrenerge GPCR-Signale durch Phosphorylierung des membranst{\"a}ndigen Rezeptors herunterzuregulieren. Durch einen PKC-abh{\"a}ngigen switch von Raf1 zu GRK2 konnte mit RKIP ein kardialer, endogener Inhibitor der GRK2 identifiziert werden. Es wurde in vitro und in vivo in M{\"a}usen mit myokardialer {\"U}berexpression von RKIP gezeigt, dass RKIP f{\"a}hig ist, die kontraktile Funktion von Herzmuskelzellen zu verbessern, negative kardiale Langzeitfolgen wie eine Verschlechterung der Insuffizienz, Remodeling-Prozesse wie Zunahme der Fibrosierung und eine gesteigerte Apoptoserate, sowie kardiale Rhythmusst{\"o}rungen protektiv zu beeinflussen. Um die endogene Rolle von RKIP weiter zu er{\"o}rtern, wurde in dieser Arbeit der Knockout von RKIP unter basalen Bedingungen, als auch nach transverser Aortenkonstriktion (TAC) untersucht. Zur Untersuchung physiologischer Parameter wie der Verk{\"u}rzungsfraktion, oder dem linksventrikul{\"a}rem diastolischen Durchmesser wurden echokardiographische Verfahren herangezogen. In diesen Untersuchungen zeigte sich nach dreiw{\"o}chiger TAC eine Verschlechterung der Pumpfunktion, sowie eine verst{\"a}rkte Dilatation des linken Ventrikels in RKIP-/--M{\"a}usen. Gest{\"u}tzt wurden diese Ergebnisse durch einen erh{\"o}hten pulmonalen Blutr{\"u}ckstau in RKIP-/--M{\"a}usen nach chronischer Druckbelastung. Zudem wurde an isolierten Kardiomyozyten die Kinetik von Kalzium als f{\"u}r die Kontraktion verantwortlichen Botenstoff durch intrazellul{\"a}re Fluoreszenz-Echtzeit-Messungen, sowie die Kontraktion und Relaxation auf Zell- und Sarkomerebene durch ein optisches Kamerasystem untersucht. Hier zeigte sich ohne den Einfluss β-adrenerger Stimulantien {\"a}quivalent zum basalen Ph{\"a}notyp dieser Tiere in RKIP-/--Kardiomyozyten keine Ver{\"a}nderung der Kalzium-Kinetik, sowie der Kontraktion und Relaxation auf Zell- und Sarkomerebene. Des Weiteren wurden mittels realtime PCR die Expressionslevels von Insuffizienzmarkern wie BNP und ANP, sowie von Kollagen 3 bestimmt. Der Grad der Fibrosierung wurde zus{\"a}tzlich durch Quantifizierung der fibrosierten Areale in histologischen Querschnitten untersucht. Apoptotische Ver{\"a}nderungen wurden mittels TUNEL-Assay auf histologischer Ebene bestimmt. In all diesen Untersuchungen zeigte sich ein fortgeschrittenes kardiales Remodeling in RKIP-/--M{\"a}usen nach TAC im Vergleich zu Wildtyptieren. Hand in Hand mit dem Bild einer fortgeschrittenen Herzinsuffizienz in RKIP-/--M{\"a}usen nach TAC konnte zudem in diesen Tieren eine gesteigerte Mortalit{\"a}t nach chronischer Hochdruckbelastung festgestellt werden. In Kombination mit den protektiven Eigenschaften einer kardialen RKIP-{\"U}berexpression, sowie dem positiven Effekt einer retroviralen RKIP-Transfektion sprechen diese Ergebnisse f{\"u}r RKIP als einen interessanten k{\"o}rpereigenen Angriffspunkt f{\"u}r die kontraktilit{\"a}tssteigernde Therapie der Herzinsuffizienz, den es in weiteren klinischen Studien zu untersuchen gilt.�},
  subject      = {RKIP},
  language  = {de}
}
@article{Berneiser2017,
  author    = {Berneiser, Tobias},
  title     = {Lissabonner Navigationen. Literarische Nautik und heterotopischer Stadtdiskurs in Jos{\´e} Cardoso Pires' Lisboa - Livro de Bordo},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {3},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2510-2613},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172859},
  pages     = {39-64},
  year      = {2017},
  abstract  = {This article seeks to analyse urban representation in Jos{\´e} Cardoso Pires's Lisboa - Livro de Bordo (1997), a book dedicated to the author's home city Lisbon, by focusing on its prevailing nautical and maritime imagery. This imagery as well as its tendency to design Lisbon as a city-ship shall be examined with regard to spatial construction in the Livro de Bordo. Urban sailing as well as the recurrent representations of the Portuguese capital's spaces as heterotopias will be interpreted as approaches to subvert institutional and homogenic discourses on Lisbon.},
  language  = {de}
}
@phdthesis{Bersi2017,
  author    = {Bersi, Heidi},
  title     = {Etablierung eines 3D in vitro Blutgef{\"a}ß-/Gewebemodells zur Testung spezifischer Therapeutika zur Leuk{\"a}miebehandlung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152506},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {In Deutschland erkranken j{\"a}hrlich etwa 500.000 Menschen an Krebs, wovon circa 12.000 die Diagnose „Leuk{\"a}mie" gestellt bekommen [1]. Unter den Leuk{\"a}mien weist die akute myeloische Leuk{\"a}mie (AML) die ung{\"u}nstigste Prognose auf, sodass hier erheblicher Forschungsbedarf besteht. Zus{\"a}tzlich schnitten viele potentielle Therapeutika, die sich in bisherigen pr{\"a}klinischen Testsystemen als vielversprechend erwiesen haben, in klinischen Studien schlecht ab [8]. Ziel dieser Arbeit war daher die Etablierung eines 3D in vitro Blutgef{\"a}ß-/Gewebemodells als verbessertes pr{\"a}klinisches System zur Testung von Therapeutika, die zur erfolgreichen Behandlung von Leuk{\"a}mien beitragen sollen. Das 3D Blutgef{\"a}ßmodell bestand aus humanen prim{\"a}ren Endothelzellen, welche als Monolayer auf der Serosaseite einer dezellularisierten, porzinen, intestinalen Kollagenmatrix (SIS-Ser) wuchsen. Nach 14-t{\"a}giger Zellkultur wurden dem Versuchsansatz entsprechend nichtadh{\"a}rente THP-1 Zellen (AML-M5-Zelllinie) und Tipifarnib oder entsprechende Kontrolll{\"o}sungen beziehungsweise bimolekulare Antik{\"o}rperkonstrukte mit PBMCs als Effektorzellen hinzupipettiert. Nach 5-t{\"a}giger Inkubation mit Tipifarnib beziehungsweise 24-st{\"u}ndiger Behandlung mit Antik{\"o}rperkonstrukten wurde der therapiebedingte Anstieg der Apoptoserate in den malignen THP-1 Zellen mittels durchflusszytometrischer Analyse der Modell{\"u}berst{\"a}nde ermittelt. Zum Ausschluss verbliebener und durchflusszytometrisch zu analysierender Zellen wurde, stellvertretend f{\"u}r alle Suspensionszellen, eine Anti-CD13/DAB-F{\"a}rbung durchgef{\"u}hrt, welche negativ ausfiel. M{\"o}gliche Kollateralsch{\"a}den am Endothel wurden mittels histologischen F{\"a}rbemethoden an Gewebeparaffinschnitten untersucht. In der Durchflusszytometrie zeigte Tipifarnib sowohl im 2D als auch im 3D Modell {\"a}quivalente, dosisabh{\"a}ngige und antileuk{\"a}mische Auswirkungen auf die THP-1 Zellen. Bei Applikation der Antik{\"o}rperkonstrukte ließ lediglich die Kombination beider Hemibodies signifikante Effekte auf die THP-1 Zellen erkennen. Dabei zeigten sich bei konstanten Konzentrationen der Antik{\"o}rperkonstrukte im 3D Modell deutlich h{\"o}here Apoptoseraten (58\%) als im 2D Modell (38\%). Stellt man Vergleiche von Tipifarnib mit den T-Zell-rekrutierenden Antik{\"o}rperkonstrukten an, so ließen sich im 2D Modell {\"a}hnliche Apoptoseraten in den THP-1 Zellen erzielen (jeweils 38\% bei Anwendung von 500 nM Tipifarnib). In den 3D Modellen erzielten jedoch die niedriger konzentrierten Antik{\"o}rperkonstrukte bei k{\"u}rzerer Inkubationsdauer eine noch h{\"o}here spezifische Apoptoserate in den THP-1 Zellen (im Mittel 58\%) als 500 nM Tipifarnib (mittlere Apoptoserate 40\%). Bez{\"u}glich der Nebenwirkungen ließ sich im 3D Modell nach Applikation von Antik{\"o}rperkonstrukten kein wesentlicher Einfluss auf das Endothel erkennen, w{\"a}hrend Tipifarnib/DMSO als auch die mit DMSO versetzten Kontrolll{\"o}sungen zu einer dosisabh{\"a}nigen Destruktion des urspr{\"u}nglichen Endothelzellmonolayers f{\"u}hrten. Damit stellt die hier beschriebene, hoch spezifische, Hemibody-vermittelte Immuntherapie einen vielversprechenden Ansatz f{\"u}r zuk{\"u}nftige onkologische Therapien dar. Mithilfe des etablierten humanen 3D in vitro Modells konnte im Vergleich zur konventionellen Zellkultur eine nat{\"u}rlichere Mikroumgebung f{\"u}r Zellen geschaffen und die Auswirkungen der Testsubstanzen sowohl auf maligne Zellen, als auch auf die Gef{\"a}ßstrukturen untersucht werden.},
  subject      = {Tissue Engineering},
  language  = {de}
}
@article{BertiVosselGamer2017,
  author    = {Berti, Stefan and Vossel, Gerhard and Gamer, Matthias},
  title     = {The orienting response in healthy aging: Novelty P3 indicates no general decline but reduced efficacy for fast stimulation rates},
  series = {Frontiers in Psychology},
  volume    = {8},
  journal   = {Frontiers in Psychology},
  doi       = {10.3389/fpsyg.2017.01780},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173651},
  year      = {2017},
  abstract  = {Automatic orienting to unexpected changes in the environment is a pre-requisite for adaptive behavior. One prominent mechanism of automatic attentional control is the Orienting Response (OR). Despite the fundamental significance of the OR in everyday life, only little is known about how the OR is affected by healthy aging. We tested this question in two age groups (19-38 and 55-72 years) and measured skin-conductance responses (SCRs) and event-related brain potentials (ERPs) to novels (i.e., short environmental sounds presented only once in the experiment; 10\% of the trials) compared to standard sounds (600 Hz sinusoidal tones with 200 ms duration; 90\% of the trials). Novel and standard stimuli were presented in four conditions differing in the inter-stimulus interval (ISI) with a mean ISI of either 10, 3, 1, or 0.5 s (blocked presentation). In both age groups, pronounced SCRs were elicited by novels in the 10 s ISI condition, suggesting the elicitation of stable ORs. These effects were accompanied by pronounced N1 and frontal P3 amplitudes in the ERP, suggesting that automatic novelty processing and orientation of attention are effective in both age groups. Furthermore, the SCR and ERP effects declined with decreasing ISI length. In addition, differences between the two groups were observable with the fastest presentation rates (i.e., 1 and 0.5 s ISI length). The most prominent difference was a shift of the peak of the frontal positivity from around 300 to 200 ms in the 19-38 years group while in the 55-72 years group the amplitude of the frontal P3 decreased linearly with decreasing ISI length. Taken together, this pattern of results does not suggest a general decline in processing efficacy with healthy aging. At least with very rare changes (here, the novels in the 10 s ISI condition) the OR is as effective in healthy older adults as in younger adults. With faster presentation rates, however, the efficacy of the OR decreases. This seems to result in a switch from novelty to deviant processing in younger adults, but less so in the group of older adults.},
  language  = {en}
}
@article{BettsNagelSchatzschneideretal.2017,
  author    = {Betts, Jonathan and Nagel, Christopher and Schatzschneider, Ulrich and Poole, Robert and La Ragione, Robert M.},
  title     = {Antimicrobial activity of carbon monoxide-releasing molecule [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br versus multidrug-resistant isolates of Avian Pathogenic \(Escherichia\) \(coli\) and its synergy with colistin},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {10},
  doi       = {10.1371/journal.pone.0186359},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173687},
  year      = {2017},
  abstract  = {Antimicrobial resistance is a growing global concern in human and veterinary medicine, with an ever-increasing void in the arsenal of clinicians. Novel classes of compounds including carbon monoxoide-releasing molecules (CORMs), for example the light-activated metal complex [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br, could be used as alternatives/to supplement traditional antibacterials. Avian pathogenic \(Escherichia\) \(coli\) (APEC) represent a large reservoir of antibiotic resistance and can cause serious clinical disease in poultry, with potential as zoonotic pathogens, due to shared serotypes and virulence factors with human pathogenic \(E.\) \(coli\). The \(in\) \(vitro\) activity of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br against multidrug-resistant APECs was assessed via broth microtitre dilution assays and synergy testing with colistin performed using checkerboard and time-kill assays. \(In\) \(vivo\) antibacterial activity of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br alone and in combination with colistin was determined using the \(Galleria\) \(mellonella\) wax moth larvae model. Animals were monitored for life/death, melanisation and bacterial numbers enumerated from larval haemolymph. \(In\) \(vitro\) testing produced relatively high [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br minimum inhibitory concentrations (MICs) of 1024 mg/L. However, its activity was significantly increased with the addition of colistin, bringing MICs down to \(\geq\)32 mg/L. This synergy was confirmed in time-kill assays. \(In\) \(vivo\) assays showed that the combination of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br with colistin produced superior bacterial killing and significantly increased larval survival. In both \(in\) \(vitro\) and \(in\) \(vivo\) assays light activation was not required for antibacterial activity. This data supports further evaluation of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br as a potential agent for treatment of systemic infections in humans and animals, when used with permeabilising agents such as colistin.},
  language  = {en}
}
@phdthesis{Betz2017,
  author    = {Betz, Sabrina},
  title     = {Textsortenwandel in Theaterkritiken - untersucht an der Frankfurter Allgemeinen Zeitung und der S{\"u}ddeutschen Zeitung von 1950 bis 2010},
  isbn      = {978-3-945459-17-1},
  doi       = {10.25972/OPUS-14844},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148444},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Textsortenwandel in Theaterkritiken - untersucht an der Frankfurter Allgemeinen Zeitung und der S{\"u}ddeutschen Zeitung von 1950 bis 2010 Ziel der Dissertation mit dem Titel „Textsortenwandel in Theaterkritiken - untersucht an der Frankfurter Allgemeinen Zeitung und S{\"u}ddeutschen Zeitung von 1950 bis 2010" ist es, m{\"o}gliche Gemeinsamkeiten und Unterschiede in Texten der Textsorte Theaterkritik {\"u}ber einen Zeitraum von sechzig Jahren in Typographie und Sprache darzustellen. Eine eingehende Analyse aller auftretenden Ph{\"a}nomene in Lexik, Syntax, Text und Stil ist aufgrund der F{\"u}lle nicht m{\"o}glich, aber auch nicht beabsichtigt. Es wird jedoch der Versuch unternommen, ein m{\"o}glichst breites Spektrum aufzuzeigen. Aufgrund des geringen Vorkommens bestimmter Merkmale oder des idiolektalen Stils, der die Untersuchungsergebnisse u. U. verf{\"a}lscht, ist eine repr{\"a}sentative Aussage auch nicht immer m{\"o}glich. Ein Augenmerk bei der Analyse wird aufgrund der Einordnung der Theaterkritik als meinungs{\"a}ußernde Darstellungsform auf den pragmatischen Bereich sowie dessen Manifestationsformen gelegt. Einzelne journalistische Textsorten sind seit jeher ein {\"a}ußerst beliebter Gegenstand von empirischen, linguistischen Analysen. Einem großen Teil der bisher erforschten Textsorten liegt ein konventionalisiertes Muster zugrunde (z. B. Todesanzeigen oder Horoskope). Im Gegensatz zu extrem von Subjektivit{\"a}t gepr{\"a}gten Textsorten wie Kommentar oder Kritik ist die Analyse bei konventionalisierten Mustern naturgem{\"a}ß leichter zu bewerkstelligen. Da f{\"u}r die Theaterkritik fast ausschließlich journalistische, kommunikationswissenschaftliche oder theaterwissenschaftliche Literatur vorliegt, besteht linguistischer Analysebedarf. Nach der Korpusanalyse l{\"a}sst sich festhalten, dass das Gebiet der schwach konventionalisierten Textsorten in der Forschung nicht grundlos vernachl{\"a}ssigt wurde. Zwar kann eine Theaterkritik der Textsorte anhand verschiedener Kriterien zugeordnet werden, aber auch diese finden nicht durchg{\"a}ngig Verwendung. Der Rezipient kann aber auch dann entsprechende Artikel der Textsorte Theaterkritik zuordnen - wenn gewisse Kriterien nicht erf{\"u}llt sind. Deutliche Veränderungen ergeben sich in den Paratexten. W{\"a}hrend Informationen zunehmend in die Unterzeile wandern, erh{\"a}lt die Hauptzeile in Folge größtenteils persuasive Funktion (R{\"a}tsel-{\"U}berschrift). Anders als in den informierenden Textsorten, die meist eine Komprimierung des Artikelinhalts aufweisen, haben die Überschriften im Feuilleton die Aufgabe, den Leser auf den Artikel neugierig zu machen. In der Unterzeile setzt sich eine Doppelstruktur durch, die zu einem spezifischen Merkmal der Textsorte avanciert (Wertung, Anspielung, Wortspiel etc. [:] Informationsteil). Die Analyse der Lexik des Fließtextes besch{\"a}ftigt sich v. a. mit den Veränderungen innerhalb der Wortarten, der Wortbildungen, der lexikalischen Varianz, der Fremdlexik, der Phraseologismen und der Vergleiche beschäftigt. Alle genannten Bereiche stehen exemplarisch f{\"u}r die Sprache der Theaterkritik. Die durchschnittliche Satzlänge bleibt {\"u}ber die Jahre relativ konstant. Der Trend weg von hypotaktischen hin zu einfachen Sätzen setzt sich in der Theaterkritik nicht durch. Sowohl die einfachen als auch die verblosen Sätze nehmen ab, während die komplexen Sätze zunehmen. Die Intertextualität ist ein typisches Merkmal der Textsorte Theaterkritik. Entsprechende Elemente finden sich in allen Jahrgängen - mit steigender Tendenz. Ihre Verwendung stellt durchaus hohe Anforderungen an den Leser, gleichzeitig wird so aber unterhalten und ein Leseanreiz gesetzt. Die Wertung als zentrales Element der Theaterkritik ist mit den meisten Bereichen der Textsorte verwurzelt. Der Verständnisgrad der Wertungen hängt von der Bildung des Lesers ab. In der Kritik sind Informationen, interpretatorische und bildhafte Beschreibungen sowie Wertungen eng miteinander verbunden. Daher fällt es schwer, eine Trennung vorzunehmen. Was sich allerdings sagen lässt, ist, dass Wertung einen großen Teil des Textes ausmacht. Die jeweilige Gewichtung bleibt dem Autor {\"u}berlassen und richtet sich u. a. nach der jeweiligen Inszenierung und dem idiolektalen Stil des Kritikers. Der Ton hat sich insofern geändert, als dass umgangssprachliche Elemente immer größeren Eingang in die Textsorte finden. Bei der Theaterkritik kann man weniger vom Individualstil eines Autors im engeren Sinn sprechen als von einem Stil, der von der Thematik und der Kreativität sowie vom handwerklichen Können des jeweiligen Rezensenten abhängt. Der Stil hat großen Einfluss auf die einzelnen Texte und erschwert so z. T. deren Vergleichbarkeit. Abschließend lässt sich festhalten, dass den Autoren von Theaterkritiken sprachlich zwischen Bildungs- und Umgangssprache, Phraseologismen und Wortbildungen, Fremd- und Fachwortschatz, in Syntax und Textaufbau so gut wie keine Grenzen gesetzt sind. Und auch die Ausf{\"u}hrung des jeweiligen Themas ist sehr frei. Gemeinsam haben alle Texte eigentlich nur die Hauptpunkte Beschreibung, Bewertung und Information, deren Gewichtung allerdings von Text zu Text extrem schwanken kann.},
  subject      = {Frankfurter Allgemeine Zeitung},
  language  = {de}
}
@phdthesis{Bialas2017,
  author    = {Bialas, David},
  title     = {Exciton Coupling in Homo- and Heterostacks of Merocyanine and Perylene Bisimide Dyes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152418},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {In the present thesis it could be demonstrated that strong exciton coupling does not only occur between same type of chromophores but also between chromophores with different excited state energies. The coupling significantly influences the optical absorption properties of the heterostacks comprising merocyanine and perylene bisimide dyes, respectively, and is an indication for coherent energy transfer between the chromophores. In addition, bis(merocyanine)-C60 conjugates have been synthesized, which self-assemble in non-polar solvents resulting in well-defined supramolecular p/n-heterojunctions in solution. These model systems enabled femtosecond transient absorption studies on the photoinduced electron transfer process, which is a key step for the formation of charge carriers in organic solar cells.},
  subject      = {Exziton},
  language  = {de}
}
@article{BiedermannBraeuerDenneretal.2017,
  author    = {Biedermann, Benedikt and Br{\"a}uer, Stephan and Denner, Ansgar and Pellen, Mathieu and Schumann, Steffen and Thompson, Jennifer M.},
  title     = {Automation of NLO QCD and EW corrections with SHERPA and RECOLA},
  series = {European Physical Journal C},
  volume    = {77},
  journal   = {European Physical Journal C},
  number    = {492},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170615},
  year      = {2017},
  abstract  = {This publication presents the combination of the one-loop matrix-element generator Recola with the multipurpose Monte Carlo program Sherpa. Since both programs are highly automated, the resulting Sherpa +Recola framework allows for the computation of - in principle - any Standard Model process at both NLO QCD and EW accuracy. To illustrate this, three representative LHC processes have been computed at NLO QCD and EW: vector-boson production in association with jets, off-shell Z-boson pair production, and the production of a top-quark pair in association with a Higgs boson. In addition to fixed-order computations, when considering QCD corrections, all functionalities of Sherpa, i.e. particle decays, QCD parton showers, hadronisation, underlying events, etc. can be used in combination with Recola. This is demonstrated by the merging and matching of one-loop QCD matrix elements for Drell-Yan production in association with jets to the parton shower. The implementation is fully automatised, thus making it a perfect tool for both experimentalists and theorists who want to use state-of-the-art predictions at NLO accuracy.},
  language  = {en}
}
@article{BiedermannDennerDittmaieretal.2017,
  author    = {Biedermann, Benedikt and Denner, Ansgar and Dittmaier, Stefan and Hofer, Lars and J{\"a}ger, Barbara},
  title     = {Next-to-leading-order electroweak corrections to the production of four charged leptons at the LHC},
  series = {Journal of High Energy Physics},
  journal   = {Journal of High Energy Physics},
  number    = {1},
  doi       = {10.1007/JHEP01(2017)033},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171966},
  year      = {2017},
  abstract  = {We present a state-of-the-art calculation of the next-to leading-order electroweak corrections to ZZ production, including the leptonic decays of the Z bosons into μ\(^+\)μ\(^ -\)e\(^+\)e\(^-\) or μ\(^+\)μ\(^-\)μ\(^+\)μ\(^-\) final states. We use complete leading-order and next-to-leading-order matrix elements for four-lepton production, including contributions of virtual photons and all off-shell effects of Z bosons, where the finite Z-boson width is taken into account using the complex-mass scheme. The matrix elements are implemented into Monte Carlo programs allowing for the evaluation of arbitrary differential distributions. We present integrated and differential cross sections for the LHC at 13 TeV both for an inclusive setup where only lepton identification cuts are applied, and for a setup motivated by Higgs-boson analyses in the four-lepton decay channel. The electroweak corrections are divided into photonic and purely weak contributions. The former show the well-known pronounced tails near kinematical thresholds and resonances; the latter are generically at the level of ∼ -5\% and reach several -10\% in the high-energy tails of distributions. Comparing the results for μ\(^+\)μ\(^-\)e\(^+\)e\(^-\) and μ\(^+\)μ\(^-\)μ\(^+\)μ\(^-\) final states, we find significant differences mainly in distributions that are sensitive to the μ\(^+\)μ\(^-\) pairing in the μ\(^+\)μ\(^-\)μ\(^+\)μ\(^-\) final state. Differences between μ\(^+\)μ\(^-\)e\(^+\)e\(^-\) and μ\(^+\)μ\(^-\)μ\(^+\)μ\(^-\) channels due to interferences of equal-flavour leptons in the final state can reach up to 10\% in off-shell-sensitive regions. Contributions induced by incoming photons, i.e. photon-photon and quark-photon channels, are included, but turn out to be phenomenologically unimportant.},
  language  = {en}
}
@article{BiedermannDennerHofer2017,
  author    = {Biedermann, Benedikt and Denner, Ansgar and Hofer, Lars},
  title     = {Next-to-leading-order electroweak corrections to the production of three charged leptons plus missing energy at the LHC},
  series = {Journal of High Energy Physics},
  volume    = {10},
  journal   = {Journal of High Energy Physics},
  number    = {43},
  doi       = {10.1007/JHEP10(2017)043},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170219},
  year      = {2017},
  abstract  = {The production of a neutral and a charged vector boson with subsequent decays into three charged leptons and a neutrino is a very important process for precision tests of the Standard Model of elementary particles and in searches for anomalous triple-gauge-boson couplings. In this article, the first computation of next-to-leading-order electroweak corrections to the production of the four-lepton final states μ\(^{+}\)μ\(^{-}\)e\(^{+}\)ν\(_{e}\), μ\(^{+}\)μ\(^{-}\)e\(^{-}\)ν\(_{e}\), μ\(^{+}\)μ\(^{-}\)μ\(^{+}\)ν\(_{μ}\), and μ\(^{+}\)μ\(^{-}\)μ\(^{-}\)ν\(_{μ}\) at the Large Hadron Collider is presented. We use the complete matrix elements at leading and next-to-leading order, including all off-shell effects of intermediate massive vector bosons and virtual photons. The relative electroweak corrections to the fiducial cross sections from quark-induced partonic processes vary between -3\% and -6\%, depending significantly on the event selection. At the level of differential distributions, we observe large negative corrections of up to -30\% in the high-energy tails of distributions originating from electroweak Sudakov logarithms. Photon-induced contributions at next-to-leading order raise the leading-order fiducial cross section by +2\%. Interference effects in final states with equal-flavour leptons are at the permille level for the fiducial cross section, but can lead to sizeable effects in off-shell sensitive phase-space regions.},
  language  = {en}
}
@article{BiedermannDennerPellen2017,
  author    = {Biedermann, Benedikt and Denner, Ansgar and Pellen, Mathieu},
  title     = {Complete NLO corrections to W\(^{+}\)W\(^{+}\) scattering and its irreducible background at the LHC},
  series = {Journal of High Energy Physics},
  volume    = {10},
  journal   = {Journal of High Energy Physics},
  number    = {124},
  doi       = {10.1007/JHEP10(2017)124},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170157},
  year      = {2017},
  abstract  = {The process pp → μ\(^{+}\)ν\(_{μ}\)e\(^{+}\)ν\(_{e}\)jj receives several contributions of different orders in the strong and electroweak coupling constants. Using appropriate event selections, this process is dominated by vector-boson scattering (VBS) and has recently been measured at the LHC. It is thus of prime importance to estimate precisely each contribution. In this article we compute for the first time the full NLO QCD and electroweak corrections to VBS and its irreducible background processes with realistic experimental cuts. We do not rely on approximations but use complete amplitudes involving two different orders at tree level and three different orders at one-loop level. Since we take into account all interferences, at NLO level the corrections to the VBS process and to the QCD-induced irreducible background process contribute at the same orders. Hence the two processes cannot be unambiguously distinguished, and all contributions to the μ\(^{+}\)ν\(_{μ}\)e\(^{+}\)ν\(_{e}\)jj final state should be preferably measured together.},
  language  = {en}
}
@phdthesis{Bienenstein2017,
  author    = {Bienenstein, Evelyn Michaela Elise},
  title     = {Varizella-Zoster-Virus-spezifische Immunantwort unter Zytokinblockade bei Rheumatoider Arthritis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142552},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Hintergrund: Die rheumatoide Arthritis ist eine chronisch inflammatorische Autoimmunerkrankung die 0,5-1\% der Bev{\"o}lkerung betrifft und zu Arthritis und Gelenksdestruktion f{\"u}hrt. Eine wichtige Rolle bei dieser Autoimmunerkrankung nehmen die pro-inflammatorischen Zytokine wie IL-6, IFNγ, IL-1β und TNFα ein. Ihre Rolle in der Pathogenese der RA ist seit einigen Jahren das Hauptinteresse der Forschung in der Entwicklung neuer Behandlungsstrategien. Die daf{\"u}r entwickelten Biologika, auch biologische disease-modifying-anti-rheumatic-drugs (bDMARDs) genannt, greifen als monoklonale Antik{\"o}rper gezielt in diese Regelkreise ein und stellen eine neue Behandlungsoption bei Versagen der konventionellen DMARDs dar. Die Erforschung der Nebenwirkungen dieser neuen Therapieans{\"a}tze ist aktuell immer noch Inhalt zahlreicher Studien. Rationale: Die Frage, inwieweit diese Biologika zu geh{\"a}uften Reaktivierungen von Varizella-Zoster-Virus (VZV) in Form von Herpes Zoster f{\"u}hren, ist bisher aus Surveillance-Daten gezeigt worden. Die zellul{\"a}ren Mechanismen sind diesbez{\"u}glich allerdings noch unverstanden. Aus diesem Grund wurde der Einfluss von verschiedenen Biologikatherapien bei RA Patienten auf die intrazellul{\"a}re Zytokinproduktion von VZV-stimulierten CD4+ und CD8+ T-Zellen untersucht und die Zytokin-Hemmung in vitro simuliert. Methoden: Die vorliegende Arbeit untersuchte die intrazellul{\"a}re Zytokinproduktion von CD4+ und CD8+ T-Zellen von 10 gesunden und 43 an RA erkrankten Probanden in verschiedenen Therapiegruppen (Adalimumab, Tocilizumab, Rituximab und Methotrexat Monotherapie) im Rahmen einer Querschnittstudie. Die mittels Durchflusszytometrie ausgewerteten Zytokinproduktionen der verschiedenen T-Zell-Subpopulationen wurden unter viralem Stimulus (VZV) und in Kombination der verschiedenen Zytokinblockaden durchgef{\"u}hrt. Resultate: Die Ergebnisse zur Korrelation best{\"a}tigten die Annahme, dass es keine Korrelation zwischen der anti-VZV-IgG Konzentration und der Avidit{\"a}t gibt. Dies konnte sowohl f{\"u}r die RA Patienten der verschiedenen Therapiegruppen, als auch die gesunden Kontrollen gezeigt werden. Es zeigten sich zahlreiche signifikante Einfl{\"u}sse der Biologika auf die Zytokine, den gr{\"o}ßten Einfluss hatte Methotrexat auf die intrazellul{\"a}re Zytokinproduktion im Sinne einer Hemmung, insbesondere bei den aktivierten CD69+ T-Zellen und in den Memory, Effektor und TEMRA T-Zell-Subpopulationen. Bei den anderen Therapiegruppen fanden sich ebenfalls zahlreiche signifikant verminderte Zytokinproduktionen, jedoch meist eine zu den gesunden Kontrollpersonen vergleichbare intrazellul{\"a}re Zytokinproduktion, insbesondere von IFNγ, nach in vitro VZV Stimulation. Synergistische Effekte f{\"u}r die in vitro Blockade von einzelnen Zytokinen auf die intrazellul{\"a}ren Zytokin-Produktionen in CD4+ und CD8+ T-Zell-Subpopulationen konnten gezeigt werden. Diskussion: Zusammenfassend zeigt sich ein deutlicher Einfluss von Methotrexat und Biologika auf die intrazellul{\"a}re Zytokinproduktion in T-Zellen von RA Patienten, jedoch ein relativ gutes in vitro Ansprechen der intrazellul{\"a}ren Zytokinproduktion nach VZV Stimulation. Da in unserem Studiendesign jedoch intrazellul{\"a}re Zytokine gemessen wurden, kann derzeit keine definitive Aussage {\"u}ber ein m{\"o}glich erh{\"o}htes Risiko f{\"u}r VZV gemacht werden. Das virale Infektionsrisiko von Kombinationen von Zytokinblockaden ist Gegenstand weiterer Untersuchungen.},
  subject      = {Varizellen-Virus},
  language  = {de}
}
@article{BistiRogalevKarolaketal.2017,
  author    = {Bisti, F. and Rogalev, V. A. and Karolak, M. and Paul, S. and Gupta, A. and Schmitt, T. and G{\"u}ntherodt, G. and Eyert, V. and Sangiovanni, G. and Profeta, G. and Strocov, V. N.},
  title     = {Weakly-correlated nature of ferromagnetism in nonsymmorphic CrO\(_2\) revealed by bulk-sensitive soft-X-ray ARPES},
  series = {Physical Review X},
  volume    = {7},
  journal   = {Physical Review X},
  number    = {4},
  doi       = {10.1103/PhysRevX.7.041067},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172251},
  year      = {2017},
  abstract  = {Chromium dioxide CrO\(_2\) belongs to a class of materials called ferromagnetic half-metals, whose peculiar aspect is that they act as a metal in one spin orientation and as a semiconductor or insulator in the opposite one. Despite numerous experimental and theoretical studies motivated by technologically important applications of this material in spintronics, its fundamental properties such as momentumresolved electron dispersions and the Fermi surface have so far remained experimentally inaccessible because of metastability of its surface, which instantly reduces to amorphous Cr\(_2\)O\(_3\). In this work, we demonstrate that direct access to the native electronic structure of CrO\(_2\) can be achieved with soft-x-ray angle-resolved photoemission spectroscopy whose large probing depth penetrates through the Cr\(_2\)O\(_3\) layer. For the first time, the electronic dispersions and Fermi surface of CrO\(_2\) are measured, which are fundamental prerequisites to solve the long debate on the nature of electronic correlations in this material. Since density functional theory augmented by a relatively weak local Coulomb repulsion gives an exhaustive description of our spectroscopic data, we rule out strong-coupling theories of CrO\(_2\). Crucial for the correct interpretation of our experimental data in terms of the valence-band dispersions is the understanding of a nontrivial spectral response of CrO\(_2\) caused by interference effects in the photoemission process originating from the nonsymmorphic space group of the rutile crystal structure of CrO\(_2\).},
  language  = {en}
}
@phdthesis{Bittner2017,
  author    = {Bittner, Andreas},
  title     = {Innovative Materialkonzepte f{\"u}r elektrochemische Energiespeicher},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152300},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Im Rahmen der vorliegenden Arbeit wurde ein neuer Beschichtungstyp f{\"u}r die Elektrodenmaterialien von Lithium-Ionen-Akkumulatoren entwickelt und charakterisiert. Dieser besteht aus einem speziellen anorganisch-organischen Hybridpolymer, das sich bez{\"u}glich seiner Zusammensetzung und Funktion gegen{\"u}ber bestehenden Beschichtungsmaterialien abhebt. Das anorganisch-organische Netzwerk des Hybridpolymers konnte mittels Feststoff-NMR-Messungen vollst{\"a}ndig aufgekl{\"a}rt werden. Dabei zeigte sich ein stabiles anorganisches Ger{\"u}st aus hoch vernetzten Polysiloxan-Einheiten. Zus{\"a}tzliche organische Modifizierungen liegen als lange bewegliche Ketten mit funktionellen Polyethylenoxid-Einheiten vor oder sind in Form von Polyethern und Diolen vernetzt. Mit dieser speziellen Netzwerkstruktur ist es m{\"o}glich, Materialeigenschaften zu erzeugen, die {\"u}ber solche von rein anorganischen und rein organischen Beschichtungen hinausgehen. Zu den mit verschiedenen Methoden nachgewiesenen Eigenschaften z{\"a}hlen eine hohe ionische Leitf{\"a}higkeit von 10\(^{-4}\) S/cm, eine hohe Elastizit{\"a}t mit E = 63 kPa, eine hohe elektrochemische Stabilit{\"a}t bis 5,0 V vs. Li/Li\(^+\) und eine hohe thermische Stabilit{\"a}t. Eine weitere Besonderheit des neuen Beschichtungsmaterials ist die mehrstufige Vernetzung der anf{\"a}nglichen Prekursoren zu einem Hybridpolymer-Sol und dem abschließenden Hybridpolymer-Gel. Die im Beschichtungssol vorliegende Teilvernetzung der Vorstufen konnte detailliert mittels Fl{\"u}ssig-NMR-Messungen untersucht und beschrieben werden. Aus den Messungen ließ sich folgern, dass die organisch und anorganisch vernetzbaren Gruppen im Sol teilweise vernetzt vorliegen. Die sterisch erreichbaren Si-OR-Gruppen der so entstandenen Oligomere sind vorwiegend nicht hydrolysiert, wodurch deren anorganische Anbindung an die OH-Gruppen der Partikeloberfl{\"a}chen kinetisch bevorzugt ist. Damit lassen sich besonders homogene und vollst{\"a}ndig bedeckende Beschichtungen der Elektrodenmaterialien erzeugen. Dies konnte mit verschiedenen physikalischen und chemischen Methoden nachgewiesen werden: simulationsgest{\"u}tzte R{\"u}ckstreuanalysen mittels REM, hochaufgel{\"o}ste TEM-Aufnahmen sowie Elementanalysen durch EDX und XPS. Nach der Optimierung des nasschemischen Beschichtungsprozesses {\"u}ber Rotationsverdampfen ergaben sich f{\"u}r die verschiedenen Elektrodenmaterialien Li\(_4\)Ti\(_5\)O\(_{12}\), Li(Ni,Co,Mn)O\(_2\) und Li(Mn,Ni)\(_2\)O\(_4\) jeweils etwa 20 nm dicke Beschichtungen mit Hybridpolymer. Die Frage nach deren L{\"o}sungsmittelbest{\"a}ndigkeit konnte durch die Analyse von behandelten Proben mit TG, REM, XPS und ICP-OES aufgekl{\"a}rt werden. Dabei zeigte sich sowohl f{\"u}r die Behandlung mit NMP, dem klassischen L{\"o}sungsmittel bei der Elektrodenfertigung mit PVDF-Binder, als auch f{\"u}r die Behandlung mit dessen umweltschonenderem Ersatzstoff Aceton eine gute Best{\"a}ndigkeit der Beschichtung. Die Beschichtung l{\"o}ste sich in den L{\"o}sungsmitteln an, blieb allerdings als geschlossene nanoskalige Beschichtung erhalten. Lediglich gegen{\"u}ber dem L{\"o}sungsmittel H\(_2\)O, das in Kombination mit dem neuen Binder CMC eingesetzt wird, wurde eine mangelnde Schichtstabilit{\"a}t deutlich. Das daf{\"u}r verantwortliche Quellverhalten der Beschichtung konnte mittels D{\"u}nnschicht-Modellsystem und daran durchgef{\"u}hrten REM-, IR- und EPA-Untersuchungen aufgekl{\"a}rt werden. Die Optimierung des Hybridpolymer-Materials bez{\"u}glich einer besseren H\(_2\)O-Best{\"a}ndigkeit {\"u}bersteigt den Rahmen dieser Arbeit und liefert die Grundlage f{\"u}r weitere k{\"u}nftige Forschungsarbeiten. Aufgrund der vollst{\"a}ndigen Bedeckung der neuen Beschichtung, ihrer besonderen Eigenschaften und ihrer Best{\"a}ndigkeit bei der klassischen Elektrodenfertigung ist es m{\"o}glich, die Elektrodenmaterialien grundlegend hinsichtlich ihrer wichtigsten Eigenschaften zu verbessern. Hierf{\"u}r wurden sowohl {\"u}ber die NMP- als auch {\"u}ber die Aceton-Route Elektroden gefertigt und zu Halbzellen und Vollzellen verarbeitet. Die REM-Analyse der Elektroden zeigte, dass die Partikelbeschichtungen keinen negativen Einfluss auf die Homogenit{\"a}t und Morphologie der Elektroden aus{\"u}ben. Damit war es m{\"o}glich, jeweils einen direkten Vergleich von beschichteten und unbeschichteten Materialien hinsichtlich ihrer elektrochemischen Performance anzustellen. F{\"u}r die Kathodenmaterialien Li(Ni,Co,Mn)O\(_2\) und Li(Mn,Ni)\(_2\)O\(_4\) ergaben die Zyklenfestigkeits- und Impedanzmessungen klare Verbesserungen durch die Beschichtung. Verbunden mit einer Verbesserung der Energiedichte erh{\"o}hte sich bei beiden Materialien die Zyklenfestigkeit um mehr als 60 \%. Bei Li(Mn,Ni)\(_2\)O\(_4\) zeigt sich die Verbesserung in einer erh{\"o}hten Zellspannung durch das vergleichsweise hohe Redoxpotential des Materials von etwa 4,7 V vs. Li/Li\(^+\), w{\"a}hrend sich bei Li(Ni,Co,Mn)O\(_2\) die Hochvoltf{\"a}higkeit des Materials verbessert, was mit einer vergr{\"o}ßerten Speicherkapazit{\"a}t verbunden ist. Dabei ist herauszustellen, dass f{\"u}r keines der Materialien ein negativer Einfluss der d{\"u}nnen Beschichtung auf die Leistungsdichte festgestellt werden konnte. Der erwartete Mechanismus f{\"u}r die verbesserte Elektrodenfunktion durch das Hybridpolymer ist die Bildung einer physikalischen Schutzschicht in Form einer Li\(^+\)-leitf{\"a}higen Membran. Diese umgibt das Elektrodenmaterial vollst{\"a}ndig, erm{\"o}glicht die Ladungstr{\"a}gerinterkalation und sch{\"u}tzt die Elektrode gleichzeitig vor irreversiblen Reaktionen mit dem Elektrolyten. Damit verbunden ist eine verminderte Mn-Ausl{\"o}sung und eine verminderte Entwicklung von isolierenden Deckschichten aus Reaktionsprodukten wie LiF, Li\(_2\)O, Li\(_2\)CO\(_3\), was sich positiv auf die Alterung der Batteriezellen auswirkt. Die Funktion der Beschichtung wurde prim{\"a}r auf den Kathodenmaterialien demonstriert. Doch auch auf der Anodenseite wurde ihre Anwendungstauglichkeit aufgezeigt, was das große Potential der Beschichtung f{\"u}r eine breite Anwendung in Lithium-Ionen-Batterien verdeutlicht.},
  subject      = {Lithium-Ionen-Akkumulator},
  language  = {de}
}
@article{BobineauHesselbach2017,
  author    = {Bobineau, Julien and Hesselbach, Robert},
  title     = {Interview mit Prof. Dr. Elissa Pustka},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {3},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2510-2613},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172927},
  pages     = {7-17},
  year      = {2017},
  abstract  = {Interview mit Prof. Dr. Elissa Pustka},
  language  = {de}
}
@article{BocukWolffKrauseetal.2017,
  author    = {Bocuk, Derya and Wolff, Alexander and Krause, Petra and Salinas, Gabriela and Bleckmann, Annalen and Hackl, Christina and Beissbarth, Tim and Koenig, Sarah},
  title     = {The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model},
  series = {BMC Cancer},
  volume    = {17},
  journal   = {BMC Cancer},
  number    = {342},
  doi       = {10.1186/s12885-017-3342-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170853},
  year      = {2017},
  abstract  = {Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in men and women. Systemic disease with metastatic spread to distant sites such as the liver reduces the survival rate considerably. The aim of this study was to investigate the changes in gene expression that occur on invasion and expansion of CRC cells when forming metastases in the liver. Methods: The livers of syngeneic C57BL/6NCrl mice were inoculated with 1 million CRC cells (CMT-93) via the portal vein, leading to the stable formation of metastases within 4 weeks. RNA sequencing performed on the Illumina platform was employed to evaluate the expression profiles of more than 14,000 genes, utilizing the RNA of the cell line cells and liver metastases as well as from corresponding tumour-free liver. Results: A total of 3329 differentially expressed genes (DEGs) were identified when cultured CMT-93 cells propagated as metastases in the liver. Hierarchical clustering on heat maps demonstrated the clear changes in gene expression of CMT-93 cells on propagation in the liver. Gene ontology analysis determined inflammation, angiogenesis, and signal transduction as the top three relevant biological processes involved. Using a selection list, matrix metallopeptidases 2, 7, and 9, wnt inhibitory factor, and chemokine receptor 4 were the top five significantly dysregulated genes. Conclusion: Bioinformatics assists in elucidating the factors and processes involved in CRC liver metastasis. Our results support the notion of an invasion-metastasis cascade involving CRC cells forming metastases on successful invasion and expansion within the liver. Furthermore, we identified a gene expression signature correlating strongly with invasiveness and migration. Our findings may guide future research on novel therapeutic targets in the treatment of CRC liver metastasis.},
  language  = {en}
}
@article{Book2017,
  author    = {Book, Bettina},
  title     = {Komplements{\"a}tze im Spanischen},
  series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  volume    = {3},
  journal   = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik},
  issn      = {2510-2613},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172869},
  pages     = {67-80},
  year      = {2017},
  abstract  = {This paper discusses complementation strategies in Spanish, focusing on a specific construction most speakers are not aware of: the complementation clause preceded by the verb conocer. Not being a typical complement-taking verb, conocer surprises with a stable and persistent presence throughout the centuries, from Old Spanish to Modern Spanish. After giving an introduction into the field of complementation clauses and one of its main focus of study, grammatical mood, this study uses empirical data from the corpus programs CORDE, CREA and CORPES XXI to show the usage and prevalence of the construction in question. In doing so, this analysis gives a quantitative insight, exemplifying the results with several examples from all ages.},
  language  = {de}
}
@article{BornZinnerSperlich2017,
  author    = {Born, Dennis-Peter and Zinner, Christoph and Sperlich, Billy},
  title     = {The mucosal immune function is not compromised during a period of high-intensity interval training. Is it time to reconsider an old assumption?},
  series = {Frontiers in Physiology},
  volume    = {8},
  journal   = {Frontiers in Physiology},
  number    = {485},
  doi       = {10.3389/fphys.2017.00485},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158025},
  year      = {2017},
  abstract  = {Purpose: The aim of the study was to evaluate the mucosal immune function and circadian variation of salivary cortisol, Immunoglobin-A (sIgA) secretion rate and mood during a period of high-intensity interval training (HIIT) compared to long-slow distance training (LSD). Methods: Recreational male runners (n = 28) completed nine sessions of either HIIT or LSD within 3 weeks. The HIIT involved 4 × 4 min of running at 90-95\% of maximum heart rate interspersed with 3 min of active recovery while the LSD comprised of continuous running at 70-75\% of maximum heart rate for 60-80 min. The psycho-immunological stress-response was investigated with a full daily profile of salivary cortisol and immunoglobin-A (sIgA) secretion rate along with the mood state on a baseline day, the first and last day of training and at follow-up 4 days after the last day of training. Before and after the training period, each athlete's running performance and peak oxygen uptake (V·O\(_{2peak}\)) was determined with an incremental exercise test. Results: The HIIT resulted in a longer time-to-exhaustion (P = 0.02) and increased V·O\(_{2peak}\) compared to LSD (P = 0.01). The circadian variation of sIgA secretion rate showed highest values in the morning immediately after waking up followed by a decrease throughout the day in both groups (P < 0.05). With HIIT, the wake-up response of sIgA secretion rate was higher on the last day of training (P < 0.01) as well as the area under the curve (AUC\(_{G}\)) higher on the first and last day of training and follow-up compared to the LSD (P = 0.01). Also the AUC\(_{G}\) for the sIgA secretion rate correlated with the increase in V·O\(_{2peak}\) and running performance. The AUC\(_{G}\) for cortisol remained unaffected on the first and last day of training but increased on the follow-up day with both, HIIT and LSD (P < 0.01). Conclusion: The increased sIgA secretion rate with the HIIT indicates no compromised mucosal immune function compared to LSD and shows the functional adaptation of the mucosal immune system in response to the increased stress and training load of nine sessions of HIIT.},
  language  = {en}
}
@article{BornKunzSperlich2017,
  author    = {Born, Dennis-Peter and Kunz, Philipp and Sperlich, Billy},
  title     = {Reliability and validity of an agility-like incremental exercise test with multidirectional change-of-direction movements in response to a visual stimulus},
  series = {Physiological Reports},
  volume    = {5},
  journal   = {Physiological Reports},
  number    = {9},
  doi       = {10.14814/phy2.13275},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158265},
  pages     = {e13275},
  year      = {2017},
  abstract  = {The aim of the study was to evaluate the reliability and validity of cardiorespiratory and metabolic variables, that is, peak oxygen uptake (V'O\(_{2peak}\)) and heart rate (HR\(_{peak}\)), obtained from an agility-like incremental exercise test for team sport athletes. To investigate the test-retest reliability, 25 team sport athletes (age: 22 ± 3 years, body mass: 75 ± 7 kg, height: 182 ± 6 cm) performed an agility-like incremental exercise test on the SpeedCourt (SC) system incorporating multidirectional change-of-direction (COD) movements twice. For each step of the incremental SC test, the athletes covered a 40-m distance interspersed with a 10-sec rest period. Each 40 m distance was split into short sprints (2.25-6.36 m) separated by multidirectional COD movements (0°-180°), which were performed in response to an external visual stimulus. All performance and physiological data were validated with variables obtained from a ramp-like treadmill and Yo-Yo intermittent recovery level 2 test (Yo-Yo IR2). The incremental SC test revealed high test-retest reliability for the time to exhaustion (ICC = 0.85, typical error [TE] = 0.44, and CV\% = 3.88), V'O\(_{2peak}\), HR\(_{peak}\), ventilation, and breathing frequency (ICC = 0.84, 0.72, 0.89, 0.77, respectively). The time to exhaustion (r = 0.50, 0.74) of the incremental SC test as well as the peak values for V'O\(_{2}\) (r = 0.59, 0.52), HR (r = 0.75, 0.78), ventilation (r = 0.57, 0.57), and breathing frequency (r = 0.68, 0.68) were significantly correlated (P ≤ 0.01) with the ramp-like treadmill test and the Yo-Yo IR2, respectively. The incremental SC test represents a reliable and valid method to assess peak values for V'O\(_{2}\) and HR with respect to the specific demand of team sport match play by incorporating multidirectional COD movements, decision making, and cognitive components.},
  language  = {en}
}
@phdthesis{Borst2017,
  author    = {Borst, Andreas},
  title     = {Apoptosis \& senescence: cell fate determination in inhibitor-treated melanoma cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155085},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Neoplasms of the skin represent the most frequent tumors worldwide; fortunately, most of them are benign or semi-malignant and well treatable. However, the two most aggressive and deadly forms of malignant skin-neoplasms are melanoma and Merkel cell carcinoma (MCC), being responsible for more than 90\% of skin-cancer related deaths. The last decade has yielded enormous progress in melanoma therapy with the advent of targeted therapies, like BRAF or MEK inhibitors, and immune-stimulating therapies, using checkpoint antibodies targeting CTLA- 4, PD-1 or PD-L1. Very recent studies suggest that also MCC patients benefit from a treatment with checkpoint antibodies. Nevertheless, in an advanced metastatic stage, a cure for both of these aggressive malignancies is still hard to achieve: while only a subset of patients experience durable benefit from the immune-based therapies, the widely applicable targeted therapies struggle with development of resistances that inevitably occur in most patients, and finally lead to their death. The four articles included in this thesis addressed current questions concerning therapy and carcinogenesis of melanoma and MCC. Moreover, they are discussed in the light of the up-to-date research regarding targeted and immune-based therapies. In article I we demonstrated that besides apoptosis, MAPK pathway inhibition in BRAF-mutated melanoma cells also induces senescence, a permanent cell cycle arrest. These cells may provide a source for relapse, as even permanently arrested cancer cells can contribute to a pro-tumorigenic milieu. To identify molecular factors determining the differential response, we established M14 melanoma cell line derived single cell clones that either undergo cell death or arrest when treated with BRAF/MEK inhibitors. Using these single cell clones, we demonstrated in article IV that downregulation of the pro-apoptotic BH3-only protein BIK via epigenetic silencing is involved in apoptosis deficiency, which can be overcome by HDAC inhibitors. These observations provide a possible explanation for the lack of a complete and durable response to MAPK inhibitor treatment in melanoma patients, and suggest the application of HDAC inhibitors as a complimentary therapy to MAPK pathway inhibition. Concerning MCC, we scrutinized the interactions between the Merkel cell polyomavirus' (MCV) T antigens (TA) and the tumor suppressors p53 and Rb in article II and III, respectively. In article III, we demonstrated that the cell cycle master regulator Rb is the crucial target of MCV large T (LT), while it - in contrast to other polyomavirus LTs - exhibits much lower affinity to the related proteins p107 and p130. Knockdown of MCV LT led to proliferation arrest in MCC cells, which can be rescued by knockdown of Rb, but not by knockdown of p107 and p130. Contrary to Rb, restriction of p53 in MCC seems to be independent of the MCV TAs, as we demonstrated in article II. In conclusion, the presented thesis has revealed new molecular details, regarding the response of melanoma cells towards an important treatment modality and the mechanisms of viral carcinogenesis in MCC.},
  subject      = {Melanom},
  language  = {en}
}
@article{BousquetOnoratoBachertetal.2017,
  author    = {Bousquet, J. and Onorato, G. L. and Bachert, C. and Barbolini, M. and Bedbrook, A. and Bjermer, L. and Correia de Sousa, J. and Chavannes, N. H. and Cruz, A. A. and De Manuel Keenoy, E. and Devillier, P. and Fonseca, J. and Hun, S. and Kostka, T. and Hellings, P. W. and Illario, M. and Ivancevich, J. C. and Larenas-Linnemann, D. and Millot-Keurinck, J. and Ryan, D. and Samolinski, B. and Sheikh, A. and Yorgancioglu, A. and Agache, I. and Arnavielhe, S. and Bewick, M. and Annesi-Maesano, I. and Anto, J. M. and Bergmann, K. C. and Bindslev-Jensen, C. and Bosnic-Anticevich, S. and Bouchard, J. and Caimmi, D. P. and Camargos, P. and Canonica, G. W. and Cardona, V. and Carriazo, A. M. and Cingi, C. and Cogan, E. and Custovic, A. and Dahl, R. and Demoly, P. and De Vries, G. and Fokkens, W. J. and Fontaine, J. F. and Gemicioğlu, B. and Guldemond, N. and Gutter, Z. and Haahtela, T. and Hellqvist-Dahl, B. and Jares, E. and Joos, G. and Just, J. and Khaltaev, N. and Keil, T. and Klimek, L. and Kowalski, M. L. and Kull, I. and Kuna, P. and Kvedariene, V. and Laune, D. and Louis, R. and Magnan, A. and Malva, J. and Mathieu-Dupas, E. and Mel{\´e}n, E. and Menditto, E. and Morais-Almeida, M. and M{\"o}sges, R. and Mullol, J. and Murray, R. and Neffen, H. and O'Hehir, R. and Palkonen, S. and Papadopoulos, N. G. and Passalacqua, G. and P{\´e}pin, J. L. and Portejoie, F. and Price, D. and Pugin, B. and Raciborski, F. and Simons, F. E. R. and Sova, M. and Spranger, O. and Stellato, C. and Todo Bom, A. and Tomazic, P. V. and Triggiani, M. and Valero, A. and Valovirta, E. and VandenPlas, O. and Valiulis, A. and van Eerd, M. and Ventura, M. T. and Wickmann, M. and Young, I. and Zuberbier, T. and Zurkuhlen, A. and Senn, A.},
  title     = {CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: a SUNFRAIL report},
  series = {Clinical and Translational Allergy},
  volume    = {2017},
  journal   = {Clinical and Translational Allergy},
  number    = {7},
  doi       = {10.1186/s13601-017-0173-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173527},
  year      = {2017},
  abstract  = {A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75\% was observed for 14 items (50\%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.},
  language  = {en}
}
@article{BratengeierHerzogWegeneretal.2017,
  author    = {Bratengeier, Klaus and Herzog, Barbara and Wegener, Sonja and Holubyev, Kostyantyn},
  title     = {Finer leaf resolution and steeper beam edges using a virtual isocentre in concurrence to PTV-shaped collimators in standard distance - a planning study},
  series = {Radiation Oncology},
  volume    = {12},
  journal   = {Radiation Oncology},
  number    = {88},
  doi       = {10.1186/s13014-017-0826-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157543},
  year      = {2017},
  abstract  = {Purpose: Investigation of a reduced source to target distance to improve organ at risk sparing during stereotactic irradiation (STX). Methods: The authors present a planning study with perfectly target-volume adapted collimator compared with multi-leaf collimator (MLC) at reduced source to virtual isocentre distance (SVID) in contrast to normal source to isocentre distance (SID) for stereotactic applications. The role of MLC leaf width and 20-80\% penumbra was examined concerning the healthy tissue sparing. Several prescription schemes and target diameters are considered. Results: Paddick's gradient index (GI) as well as comparison of the mean doses to spherical shells at several distances to the target is evaluated. Both emphasize the same results: the healthy tissue sparing in the high dose area around the planning target volume (PTV) is improved at reduced SVID ≤ 70 cm. The effect can be attributed more to steeper penumbra than to finer leaf resolution. Comparing circular collimators at different SVID just as MLC-shaped collimators, always the GI was reduced. Even MLC-shaped collimator at SVID 70 cm had better healthy tissue sparing than an optimal shaped circular collimator at SID 100 cm. Regarding penumbra changes due to varying SVID, the results of the planning study are underlined by film dosimetry measurements with Agility™ MLC. Conclusion: Penumbra requires more attention in comparing studies, especially studies using different planning systems. Reduced SVID probably allows usage of conventional MLC for STX-like irradiations.},
  language  = {en}
}
@unpublished{BraunschweigBruecknerDeissenbergeretal.2017,
  author    = {Braunschweig, Holger and Br{\"u}ckner, Tobias and Deißenberger, Andrea and Dewhurst, Rian and Gackstatter, Annika and G{\"a}rtner, Annalena and Hofmann, Alexander and Kupfer, Thomas and Prieschl, Dominic and Thiess, Torsten and Wang, Sunewang Rixin},
  title     = {Reaction of Dihalodiboranes(4) with N-Heterocyclic Silylenes: Facile Construction of 1-Aryl-2-Silyl-1,2-Diboraindanes},
  series = {Chemistry, A European Journal},
  journal   = {Chemistry, A European Journal},
  doi       = {10.1002/chem.201702377},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153068},
  year      = {2017},
  abstract  = {Dihalodiboranes(4) react with an N-heterocyclic silylene (NHSi) to generate NHSi-adducts of 1-aryl-2-silyl-1,2-diboraindanes as confirmed by X-ray crystallography, featuring the functionalization of both B-X (X = halogen) bonds and a C-H bond under mild conditions. Coordination of a third NHSi to the proposed 1,1-diaryl- 2,2-disilyldiborane(4) intermediates, generated by a two-fold B-X insertion, may be crucial for the C-H borylation that leads to the final products. Notably, our results demonstrate the first C-H borylation with a strong B-F bond activated by silylene insertion.},
  language  = {en}
}
@phdthesis{Brendel2017,
  author    = {Brendel, Michael},
  title     = {Correlation between Interface Energetics of Molecular Semiconductors and Opto-Electronic Properties of Planar Organic Solar Cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155094},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {It was the scope of this work to gain a deeper understanding of the correlation between Interface energetics of molecular semiconductors in planar organic solar cells and the corresponding optoelectronic characteristics. For this aim, different approaches were followed. At first, a direct variation of donor/acceptor (D/A) interface energetics of bilayer cells was achieved by utilizing systematically modified donor compounds. This change could be correlated to the macroscopic device performance. At second, the impact of interface energetics was illustrated, employing a more extended device architecture. By introducing a thin interlayer between a planar D/A heterojunction, an energetic staircase was established. Exciton dissociation in such devices could be linked to the cascade energy level alignment of the photo-active materials. Finally, two different fullerene molecules C60 and C70 were employed in co-evaporated acceptor phases. The expected discrepancy in their electronic structure was related to the transport properties of the corresponding organic photovoltaic cells (OPVCs). The fullerenes are created simultaneously in common synthesis procedures. Next to the photo-physical relevance, the study was carried-out to judge on the necessity of separating the components from each other by purification which constitutes the cost-determining step in the total production costs.},
  subject      = {Organische Solarzelle},
  language  = {en}
}
@book{Brix2017,
  author    = {Brix, Kerstin},
  title     = {Die deutsche Sueton{\"u}bersetzung Jakob Vielfelds (1536). Transkript nach dem Digitalisat der Bayerischen Staatsbibliothek M{\"u}nchen (Res/2 A.lat.b. 705; VD16 S 10107)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152831},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  pages     = {197},
  year      = {2017},
  abstract  = {Der vorliegende Text ist das Transkript der ersten deutschen Gesamt{\"u}bersetzung von Suetons Kaiserviten, die 1536 bei dem Straßburger Drucker Jakob Cammerlander erschien und die in der Dissertation „Sueton in Straßburg. Die {\"U}bersetzung der Kaiserviten durch Jakob Vielfeld (1536)" (Spolia Berolinensia; Verlag Olms, Hildesheim 2017) umfassend untersucht worden ist. Das Transkript pr{\"a}sentiert diese {\"U}bersetzung, obwohl Digitalisate des Cammerlanderdruckes existieren. Dem liegt zugrunde, dass das Transkript im Zuge der erw{\"a}hnten Dissertation entstand, deren Zentrum der direkte und detaillierte Textvergleich bildet; der Nachvollzug dieses Textvergleichs sollte mithilfe des entsprechend aufbereiteten Transkripts erleichtert werden. Außerdem war es das Ziel, neben den Detailuntersuchungen auch den bisher wenig beachteten deutschen Sueton als ganzen st{\"a}rker zur Geltung zu bringen. Aber auch ohne die Konsultation der Studie kann das Transkript Grundlage f{\"u}r den bequemen Vergleich der {\"U}bersetzung mit dem lateinischen Text in der Referenzausgabe von Maximilian Ihm (editio maior, 1907) sein. Gegen{\"u}ber dem digitalisierten Druck sind die deutschen Kaiserviten besonders durch zwei Eingriffe f{\"u}r moderne Leser aufbereitet worden: Zum einen enth{\"a}lt der fr{\"u}hneuzeitliche Druck keine Abschnittsz{\"a}hlung, sodass es umst{\"a}ndlicher ist, fr{\"u}hneuhochdeutsche Textstellen den entsprechenden Passagen in der Ausgabe Ihms zuzuordnen, und so ist das Transkript durchg{\"a}ngig mit Abschnittsziffern ausgestattet, die sich an der lateinischen Edition orientieren. Zum anderen kommen bei der Wiedergabe der deutschen {\"U}bersetzung - auch dies in Analogie zu Ihms Ausgabe - konsequent moderne Interpunktionsregeln zum Einsatz, wodurch sich die gedanklichen Strukturen des Textes leichter {\"u}berblicken lassen und dieser insgesamt fl{\"u}ssiger zu lesen ist.},
  language  = {de}
}
@article{BrodehlBelkeGarnettetal.2017,
  author    = {Brodehl, Andreas and Belke, Darrell D. and Garnett, Lauren and Martens, Kristina and Abdelfatah, Nelly and Rodriguez, Marcela and Diao, Catherine and Chen, Yong-Xiang and Gordon, Paul M. K. and Nygren, Anders and Gerull, Brenda},
  title     = {Transgenic mice overexpressing desmocollin-2 (DSC2) develop cardiomyopathy associated with myocardial inflammation and fibrotic remodeling},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0174019},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171084},
  pages     = {e0174019},
  year      = {2017},
  abstract  = {Background Arrhythmogenic cardiomyopathy is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure, mainly as a result of mutations in cardiac desmosomal genes. Desmosomes are cell-cell junctions mediating adhesion of cardiomyocytes; however, the molecular and cellular mechanisms underlying the disease remain widely unknown. Desmocollin-2 is a desmosomal cadherin serving as an anchor molecule required to reconstitute homeostatic intercellular adhesion with desmoglein-2. Cardiac specific lack of desmoglein-2 leads to severe cardiomyopathy, whereas overexpression does not. In contrast, the corresponding data for desmocollin-2 are incomplete, in particular from the view of protein overexpression. Therefore, we developed a mouse model overexpressing desmocollin-2 to determine its potential contribution to cardiomyopathy and intercellular adhesion pathology. Methods and results We generated transgenic mice overexpressing DSC2 in cardiac myocytes. Transgenic mice developed a severe cardiac dysfunction over 5 to 13 weeks as indicated by 2D-echocardiography measurements. Corresponding histology and immunohistochemistry demonstrated fibrosis, necrosis and calcification which were mainly localized in patches near the epi- and endocardium of both ventricles. Expressions of endogenous desmosomal proteins were markedly reduced in fibrotic areas but appear to be unchanged in non-fibrotic areas. Furthermore, gene expression data indicate an early up-regulation of inflammatory and fibrotic remodeling pathways between 2 to 3.5 weeks of age. Conclusion Cardiac specific overexpression of desmocollin-2 induces necrosis, acute inflammation and patchy cardiac fibrotic remodeling leading to fulminant biventricular cardiomyopathy.},
  language  = {en}
}
@article{BrumbergKuestersAlMomanietal.2017,
  author    = {Brumberg, Joachim and K{\"u}sters, Sebastian and Al-Momani, Ehab and Marotta, Giorgio and Cosgrove, Kelly P. and van Dyck, Christopher H. and Herrmann, Ken and Homola, Gy{\"o}rgy A. and Pezzoli, Gianni and Buck, Andreas K. and Volkmann, Jens and Samnick, Samuel and Isaias, Ioannis U.},
  title     = {Cholinergic activity and levodopa-induced dyskinesia: a multitracer molecular imaging study},
  series = {Annals of Clinical and Translational Neurology},
  volume    = {4},
  journal   = {Annals of Clinical and Translational Neurology},
  number    = {9},
  doi       = {10.1002/acn3.438},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170406},
  pages     = {632-639},
  year      = {2017},
  abstract  = {Objective: To investigate the association between levodopa-induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease. Methods: This study included 13 Parkinson's disease patients with peak-of-dose levodopa-induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5-[\(^{123}\)I]iodo-3-[2(S)-2-azetidinylmethoxy]pyridine single-photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [\(^{123}\)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography, to measure dopamine reuptake transporter density and 2-[\(^{18}\)F]fluoro-2-deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed. Results: Density of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side. Interpretation: Our findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic-depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression.},
  language  = {en}
}
@phdthesis{Brunner2017,
  author    = {Brunner, Thomas},
  title     = {Nutzen eines implantierten Event Recorders zur Detektion von klinisch relevanten Rhythmusst{\"o}rungen bei Patienten mit fortgeschrittener Fabry - Kardiomyopathie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155528},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Der Morbus Fabry ist eine X-chromosomal rezessive, lysosomale Speicherkrankheit, die durch eine Mutation im α - Galactosidase A Gen verursacht wird. Dadurch werden unter anderem Bestandteile der Plasmamembran (Globotriaosylceramide) nicht mehr degradiert und sie akkumulieren intrazellul{\"a}r. Daraus resultiert, vom anf{\"a}nglichen Einzelzellsch{\"a}den, letzten Endes ein oftmals schwerer Organschaden mit Funktionsausf{\"a}llen. Die einzige kausale Therapie besteht in der Substituierung des betroffenen Enzyms. Der Morbus Fabry {\"a}ußert sich klinisch als eine Multisystemerkrankung mit haupts{\"a}chlich renaler, nervaler, sowie kardialer Beteiligung. Vor allem letztere ist maßgeblich f{\"u}r die verk{\"u}rzte Lebenserwartung verantwortlich. Die Patienten entwickeln mit Progression der Erkrankung h{\"a}ufig eine linksventrikul{\"a}re Hypertrophie, eine Herzinsuffizienz und durch die zunehmende Akkumulation der Globotriaosylceramide entsteht im Verlauf ein fibrotischer Umbau im Myokard. Dies ist m{\"o}glicherweise auch der Entstehungsort f{\"u}r maligne Rhythmusst{\"o}rungen. Wissenschaftlich erforscht ist, dass supraventikul{\"a}re sowie ventrikul{\"a}re Tachykardien bzw. Bradykardien bis hin zu Asystolie/Pausen bei diesen Patienten auftreten k{\"o}nnen. Ebenso weiß man, dass man mit Hilfe von so genannten Event Recordern, die kontinuierlich die elektrische Herzaktivit{\"a}t {\"u}berwachen und die Daten via Telemetrie an ein Zentrum senden, die Detektionsrate von Rhythmusst{\"o}rungen erh{\"o}hen kann. Aber ob solch ein Event Recorder auch bei Patienten mit fortgeschrittener Fabry - Kardiomyopathie einen Nutzen hat und sie bei diesen Patienten zur Detektion von malignen Rhythmusst{\"o}rungen beitragen ist bisher unklar und Thema dieser Studie. Insgesamt implantierte man 16 Patienten (12 M{\"a}nner / 4 Frauen), mit einem gesicherten Morbus Fabry, einen Event Recorder. Sie erhielten 7,4 ± 4,5 Jahren die Enzymersatztherapie, wurden {\"u}ber einen Zeitraum von 0,3 - 2 Jahren beobachtet und {\"u}bertrugen ihre Daten durchschnittlich 14 ± 11 mal pro Monat. Dabei konnten insgesamt 8547 klinisch relevante {\"U}bertragungen aufgezeichnet werden, die entsprechend der Studieneinteilung in Asystolie, Bradykardie, Vorhofflimmern, und ventrikul{\"a}re Tachykardie eingeteilt worden sind. Asystolie Episoden, mit elektrischen Pausen von 3,3 bis 4,4 Sekunden, wurden insgesamt 66-mal bei 4 Patienten mit dem Event Recorder aufgezeichnet. {\"U}ber 8000 Bradykardien konnten bei 6 M{\"a}nnern und 1 Frau dokumentiert werden, darunter ein AV-Block II° Typ Mobitz mit ei ner 2:1 {\"U}berleitung. Fast 370-mal konnte ein intermittierendes Vorhofflimmern bzw. Vorhofflattern, mit Flimmerzeiten von 10 Sekunden bis maximal 86400 Sekunden, dargestellt werden. Bei insgesamt 5 Patienten konnten 10 ventrikul{\"a}re Tachykardie - Episoden, mit einer maximalen Herzfrequenz 206 Schl{\"a}gen / min, durch den Event Recorder aufgezeichnet werden. So konnten selbst bei dieser kleinen Kohorte, mit dem Event Recorder, viele klinisch relevante Herzrhythmusst{\"o}rungen detektiert werden. Auf Grundlage dieser Daten sprach man im Verlauf bei den entsprechenden Patienten eine Empfehlung zur Therapie{\"a}nderungen aus um klinische Komplikationen zu verhindern. Dies f{\"u}hrte letzten Endes zu der Schlussfolgerung, dass der Einsatz von Event Recordern sicherlich ein sehr n{\"u}tzliches diagnostisches Instrument zur Detektion von malignen Rhythmusst{\"o}rungen bei Patienten mit einer fortgeschrittenen Fabry-Kardiomyopathie ist. Es sollte nun weiter gepr{\"u}ft werden, ob der Event Recorder bereits in fr{\"u}heren Stadien des Morbus Fabry zum Einsatz kommen sollte.},
  subject      = {Fabry Kardiomyopathie},
  language  = {de}
}
@phdthesis{Brueckner2017,
  author    = {Br{\"u}ckner, Charlotte},
  title     = {The Electronic Structure and Optoelectronic Processes at the Interfaces in Organic Solar Cells Composed of Small Organic Molecules - A Computational Analysis of Molecular, Intermolecular, and Aggregate Aspects},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141652},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Describing the light-to-energy conversion in OSCs requires a multiscale understanding of the involved optoelectronic processes, i.e., an understanding from the molecular, intermolecular, and aggregate perspective. This thesis presents such a multiscale description to provide insight into the processes in the vicinity of the organic::organic interface, which are crucial for the overall performance of OSCs. Light absorption, exciton diffusion, photoinduced charge transfer at the donor-acceptor interface, and charge separation are included. In order to establish structure-property relationships, a variety of different molecular p-type semiconductors are combined at the organic donor-acceptor heterojunction with fullerene C60, one of the most common acceptors in OSCs. Starting with a comprehensive analysis of the accuracy of diverse ab initio, DFT, and semiempiric methods for the properties of the individual molecules, the intermolecular, and aggregate/device stage are subsequently addressed. At all stages, both methodological concepts and physical aspects in OSCs are discussed to extend the microscopic understanding of the charge generation processes.},
  subject      = {Benchmark},
  language  = {en}
}
@phdthesis{Bruehlmann2017,
  author    = {Br{\"u}hlmann, David},
  title     = {Tailoring Recombinant Protein Quality by Rational Media Design},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147345},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Nowadays, more than half of the biotherapeutics are produced in mammalian cell lines as a result of correct protein folding and assembly as well as their faculty to bring about a variety of post-translational modifications. The widespread progression of biosimilars has moved the focus in mammalian cell-culture process development. Thereby, the modulation of quality attributes of recombinant therapeutic proteins has increasingly gained importance from early process development stages. Protein quality directly shapes the clinical efficacy and safety in vivo, and therefore, the control of the complex post-translational modifications, such as glycosylation (e.g. high mannose, fucosylation, galactosylation and sialylation), charge variants, aggregates and low-molecular-weight species formation, is pivotal for efficient receptor binding and for triggering the desired immune responses in patients. In the frame of biosimilar development, product quality modulation methods using the potential of the host cell line are particularly sought after to match the quality profile of the targeted reference medicinal product (RMP) as closely as possible. The environment the cell is dwelling in directly influences its metabolism and the resulting quality profile of the expressed protein. Thereby the cell culture medium plays a central role in upstream manufacturing. In this work, concentration adjustment of selected media components and supplementation with a variety of compounds was performed to alter various metabolic pathways, enzyme activities and in some cases the gene expression levels of Chinese Hamster Ovary (CHO) cells in culture. The supplementation of cell culture medium with the trisaccharide raffinose in fed-batch cultures entailed an increase of the abundance of high mannose glycans in two different CHO cell lines. Raffinose especially favored mannose 5 glycans. At the same time, it impaired cell culture performance, induced changes on the intracellular nucleotide levels and even varied the expression levels of glycosylation-related genes. Supplementation with a number of galactosyltransferase inhibiting compounds, in particular fluorinated galactose analogs (alpha- and beta-2F-peracetyl-galactose), consistently decreased the production of galactosylated monoclonal antibodies (mAb). By means of targeted addition during the culture rather than at the beginning, the inhibition was further increased, while limiting detrimental effects on both growth and productivity. High-throughput screening in 96-deepwell plates showed that spermine and L-ornithine also reduced the level of galactosylation. On the other hand, exploratory screening of a variety of potentially disulfide-bridge-reducing agents highlighted that the inherent low-molecular-species level of the proprietary platform cell culture process was likely due to favored reduction. This hypothesis was reinforced by the observation that supplementation of cysteine and N-acetylcysteine promoted fragmentation. Additionally, fragmentation decreased with higher protein expression. At that point, aiming to improve the efficiency in process development, a rational experimental design method was developed to identify and to define the optimal concentration range of quality modulating compounds by calling on a combination of high throughput fed-batch testing and multivariate data analysis. Seventeen medium supplements were tested in five parallel 96-deepwell plate experiments. The selection process of promising modulators for the follow-up experiment in shake tubes consisted in a three-step procedure, including principal component analysis, quantitative evaluation of their performance with respect to the specifications for biosimilarity and selection following a hierarchical order of decisions using a decision tree. The method resulted in a substantial improvement of the targeted glycosylation profile in only two experimental rounds. Subsequent development stages, namely validation and transfer to industrial-scale facilities require tight control of product quality. Accordingly, further mechanistic understanding of the underlying processes was acquired by non-targeted metabolomic profiling of a CHO cell line expressing a mAb cultured in four distinct process formats. Univariate analysis of intra- and extracellular metabolite and temporal glycosylation profiles provided insights in various pathways. The numerous of parameters were the main driver to carry out principal component analysis, and then, using the methodology of partial-least-square (PLS) projection on latent structures, a multivariate model was built to correlate the extracellular data with the distinct glycosylation profiles. The PLS observation model proved to be reliable and showed its great benefit for glycan pattern control in routine manufacturing, especially at large scale. Rather than relying on post-production interpretation of glycosylation results, glycosylation can be predicted in real-time based on the extracellular metabolite levels in the bioreactor. Finally, for the bioactivity assessment of the glycan differences between the biosimilar and the reference medicinal product (RMP), the health agencies may ask for in the drug registration process, extended ranges of glycan variants need to be generated so that the in vitro assays pick up the changes. The developed glycosylation modulator library enabled the generation of extreme glycosylation variants, including high mannose, afucosylated, galactosylated as well as sialic acid species of both a mAb and an antibody fusion molecule with three N-glycosylation sites. Moreover, to create increased variety, enzymatic glycoengineering was explored for galactosylation and sialylation. The glyco variants induced significant responses in the respective in vitro biological activity assays. The data of this work highlight the immense potential of cell culture medium optimization to adjust product quality. Medium and feed supplementation of a variety of compounds resulted in reproducible and important changes of the product quality profile of both mAbs and a fusion antibody. In addition to the intermediate modulation ranges that largely met the requirements for new-biological-entity and biosimilar development, medium supplementation even enabled quick and straightforward generation of extreme glycan variants suitable for biological activity testing.},
  subject      = {Zellkultur},
  language  = {en}
}
@article{BuffBrinkmannBruchmannetal.2017,
  author    = {Buff, Christine and Brinkmann, Leonie and Bruchmann, Maximilian and Becker, Michael P.I. and Tupak, Sara and Herrmann, Martin J. and Straube, Thomas},
  title     = {Activity alterations in the bed nucleus of the stria terminalis and amygdala during threat anticipation in generalized anxiety disorder},
  series = {Social Cognitive and Affective Neuroscience},
  volume    = {12},
  journal   = {Social Cognitive and Affective Neuroscience},
  number    = {11},
  doi       = {10.1093/scan/nsx103},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173298},
  pages     = {1766-1774},
  year      = {2017},
  abstract  = {Sustained anticipatory anxiety is central to Generalized Anxiety Disorder (GAD). During anticipatory anxiety, phasic threat responding appears to be mediated by the amygdala, while sustained threat responding seems related to the bed nucleus of the stria terminalis (BNST). Although sustained anticipatory anxiety in GAD patients was proposed to be associated with BNST activity alterations, firm evidence is lacking. We aimed to explore temporal characteristics of BNST and amygdala activity during threat anticipation in GAD patients. Nineteen GAD patients and nineteen healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during a temporally unpredictable threat anticipation paradigm. We defined phasic and a systematic variation of sustained response models for blood oxygen level-dependent responses during threat anticipation, to disentangle temporally dissociable involvement of the BNST and the amygdala. GAD patients relative to HC responded with increased phasic amygdala activity to onset of threat anticipation and with elevated sustained BNST activity that was delayed relative to the onset of threat anticipation. Both the amygdala and the BNST displayed altered responses during threat anticipation in GAD patients, albeit with different time courses. The results for the BNST activation hint towards its role in sustained threat responding, and contribute to a deeper understanding of pathological sustained anticipatory anxiety in GAD.},
  language  = {en}
}
@phdthesis{Burger2017,
  author    = {Burger, Valentin},
  title     = {Performance Evalution and Optimization of Content Delivery Networks},
  issn      = {1432-8801},
  doi       = {10.25972/OPUS-15276},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152769},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Content Delivery Networks (CDNs) are networks that distribute content in the Internet. CDNs are increasingly responsible for the largest share of traffic in the Internet. CDNs distribute popular content to caches in many geographical areas to save bandwidth by avoiding unnecessary multihop retransmission. By bringing the content geographically closer to the user, CDNs also reduce the latency of the services. Besides end users and content providers, which require high availability of high quality content, CDN providers and Internet Service Providers (ISPs) are interested in an efficient operation of CDNs. In order to ensure an efficient replication of the content, CDN providers have a network of (globally) distributed interconnected datacenters at different points of presence (PoPs). ISPs aim to provide reliable and high speed Internet access. They try to keep the load on the network low and to reduce cost for connectivity with other ISPs. The increasing number of mobile devices such as smart phones and tablets, high definition video content and high resolution displays result in a continuous growth in mobile traffic. This growth in mobile traffic is further accelerated by newly emerging services, such as mobile live streaming and broadcasting services. The steep increase in mobile traffic is expected to reach by 2018 roughly 60\% of total network traffic, the majority of which will be video. To handle the growth in mobile networks, the next generation of 5G mobile networks is designed to have higher access rates and an increased densification of the network infrastructure. With the explosion of access rates and number of base stations the backhaul of wireless networks will become congested. To reduce the load on the backhaul, the research community suggests installing local caches in gateway routers between the wireless network and the Internet, in base stations of different sizes, and in end-user devices. The local deployment of caches allows keeping the traffic within the ISPs network. The caches are organized in a hierarchy, where caches in the lowest tier are requested first. The request is forwarded to the next tier, if the requested object is not found. Appropriate evaluation methods are required to optimally dimension the caches dependent on the traffic characteristics and the available resources. Additionally methods are necessary that allow performance evaluation of backhaul bandwidth aggregation systems, which further reduce the load on the backhaul. This thesis analyses CDNs utilizing locally available resources and develops the following evaluations and optimization approaches: Characterization of CDNs and distribution of resources in the Internet, analysis and optimization of hierarchical caching systems with bandwidth constraints and performance evaluation of bandwidth aggregation systems.},
  subject      = {CDN-Netzwerk},
  language  = {en}
}
@phdthesis{Butzmann2017,
  author    = {Butzmann, Elias},
  title     = {Natur- und {\"O}kotourismus im Nationalpark Berchtesgaden : Eine segment- und produktspezifische Analyse unter Anwendung der Product-based Typology for Nature-based Tourism},
  publisher = {W{\"u}rzburg University Press},
  address   = {W{\"u}rzburg},
  isbn      = {978-3-95826-048-1 (print)},
  doi       = {10.25972/WUP-978-3-95826-049-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141430},
  school      = {Universit{\"a}t W{\"u}rzburg},
  pages     = {368},
  year      = {2017},
  abstract  = {Schutzgebiete und insbesondere Nationalparke haben nach den Richtlinien der IUCN ein Doppelmandat bzw. eine doppelte Funktion: Sie sollen zum einen R{\"a}ume f{\"u}r Natur- und Artenschutz und zum anderen f{\"u}r Erholung, Umweltbildung und Tourismus bieten und durch letztgenanntes zur St{\"a}rkung der Regional{\"o}konomie beitragen. Um diesen Spagat zu meistern, sollten sich Schutzgebiete bzw. deren Verwaltungen und kooperierende Destinationsmarketingorganisationen dar{\"u}ber im Klaren sein, welche Besuchersegmente bzw. Tourismusprodukte im Schutzgebiet anzutreffen sind, bzw. angeboten werden und welchen Einfluss diese auf die Erf{\"u}llung des Doppelmandates haben. Die deduktiv entworfene Product-based Typology for Nature-based Tourism von ARNEGGER et al. (2010) bietet hierf{\"u}r einen zweidimensionalen Analyserahmen, der die Angebots- und Nachfrageperspektive auf den Tourismus und dessen Produkte vereint und bisher noch nicht empirisch angewendet wurde, was das vorrangige Ziel dieser Studie ist. Hierf{\"u}r wurde von Theorien und empirischen Studien aus dem Kontext von Natur- und {\"O}kotourismus eine Operationalisierung der Typologie abgeleitet, die am Beispiel des Nationalparks Berchtesgaden eingesetzt wurde. Dabei wurden zwei Ans{\"a}tze verfolgt, eine angebotsseitige und eine nachfrageseitige Abgrenzung von Tourismusprodukten. Zur empirischen Erfassung von Tourismusprodukten wurde eine umfassende Besucherbefragung in der Sommersaison 2014 durchgef{\"u}hrt, bei der Informationen von rund 1.400 Besuchern des Nationalparks gesammelt werden konnten. Aus Sicht der Nachfrager wurden sechs Produkt-Cluster identifiziert, die sich bez{\"u}glich Reiseaktivit{\"a}ten und Motiven unterscheiden. Das mit der h{\"o}chsten Naturaffinit{\"a}t ist das Produkt-Cluster der „Naturbildungsurlauber" bzw. der „{\"O}kotouristen". Auf der anderen Seite des Spektrums stehen die „Passiven Erholungsurlauber" mit einer geringen Nationalparkaffinit{\"a}t. Des Weiteren wurden spezifische Tourismusprodukte aus der Angebotsperspektive, wie Exkursionen der Nationalparkverwaltung oder mehrt{\"a}gige gef{\"u}hrte Wanderungen von spezialisierten Nischenreiseveranstaltern, identifiziert. Nach der empirischen Abgrenzung der Produkte wurden diese dahingehend {\"u}berpr{\"u}ft, ob sie sich bez{\"u}glich {\"o}konomischer und {\"o}kologischer Indikatoren unterscheiden, um zu eruieren, inwieweit die Segmente aus Sicht einer nachhaltigen Regionalentwicklung bzw. aus Sicht des Doppelmandats zu beurteilen sind. Auch hier schneiden etwa die Naturbildungsurlauber relativ gut ab, da sie Muster von structured ecotourism aufweisen und sich durch eine hohe Naturaffinit{\"a}t, positive Einstellungen zu nachhaltigem Tourismus und relativ hohe Reiseausgaben auszeichnen. Bei drei Clustern zeigt sich ein gewisser trade-off: W{\"a}hrend die Bergsteiger aus {\"o}kologischer jedoch nicht aus {\"o}konomischer Perspektive interessant sind, ist dies bei den allgemeinen Vergn{\"u}gungs- und Naturerlebnisurlaubern und den passiven Erholungsurlaubern genau umgekehrt. Basierend auf den Ergebnissen werden m{\"o}gliche Adaptionen der Typologie diskutiert und darauf aufbauend ein Analyserahmen f{\"u}r eine „Typologie f{\"u}r Nachhaltige Park-Tourismus Produkte" erarbeitet. Zudem werden theoretische und erste praktische Implikationen f{\"u}r das Management von Schutzgebiets-Destinationen diskutiert, um unter Ber{\"u}cksichtigung der trade-offs das Produktportfolio weiterzuentwickeln, das eine Destination auf den Pfad des sogenannten enlightened mass tourism bringen kann.},
  subject      = {{\"O}kotourismus},
  language  = {de}
}
@phdthesis{Baer2017,
  author    = {B{\"a}r, Isabel},
  title     = {Einsatz biokompatibler Polymermembranen zur Therapie kongenitaler Bauchwanddefekte im Rattenmodell},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154161},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Kongenitale Bauchwanddefekte sind dramatische Fehlbildungen der vorderen Bauchwand. Zu den Defekten geh{\"o}ren neben der Nabelhernie und dem Blasenextrophie-Komplex im engeren Sinne die Gastroschisis und die Omphalozele. Die Therapie stellt die behandelnden Kinderchirurgen und Neonatologen vor eine große Herausforderung. Methode der Wahl ist der prim{\"a}r operative Bauchdeckenverschluss. Falls aufgrund der Gr{\"o}ße des abdominellen Defekts oder der viszeroabdominellen Diskrepanz ein prim{\"a}rer Verschluss nicht m{\"o}glich ist, wird eine Schusterplastik angelegt oder ein Patch implantiert. Bei den Implantaten unterscheidet man nicht-resorbierbare Materialien wie Polypropylen und Polytetrafluorethylene (GoreTex®) von resorbierbaren Patchs wie zum Beispiel humane Dura, porkine D{\"u}nndarmsubmukosa, oder azellularisiertes Rinderperikard (Lyoplant®). Die Anspr{\"u}che an ein solches Implantat sind hoch und das perfekte Material wurde bis heute noch nicht gefunden. Ideale Eigenschaften sind eine gute Handhabung und N{\"a}hbarkeit, Resorbierbarkeit, Anti-Adh{\"a}sivit{\"a}t zum Intestinum, Stabilit{\"a}t und Elastizit{\"a}t sowie die Transplantatakzeptanz. Ziel dieser Arbeit war die Etablierung bipolarer Polymermembranen zur sicheren und effektiven Therapie kongenitaler Bauchwanddfekten im Rattenmodell. Bei den Polymermembranen handelt es sich um zweischichtige Implantate, welche aus einem Film und einem aufgesponnen Vlies bestehen. Der Film besteht aus dem Resomer LR708, dem linearen PEG-PLA und dem Polyurethan CW1681. Der mittels Electrospinning auf den Film aufgebrachte Vlies ist aus reinem PLA. Die Implantate sind zwischen 20 und 67 µm dick. Als Vergleich diente das bereits im Klein- und Großtiermodell von Meyer et al. etablierte Kollagen-Mesh Lyoplant®. Als Versuchstiere des Experiments dienten n=34 m{\"a}nnliche Wistar Furth Ratten, denen intraoperativ ein 2 x 2 cm großer Bauchwanddefekt zugef{\"u}hrt wurde, der anschließend mit einem gleich großen Patch verschlossen wurde. N=25 Tiere erhielten eine bipolare Polymermebran, n=2 Tiere Lyoplant und n=7 Ratten dienten zur Kontrolle. Nach 21 Tagen fand ein erneuter Eingriff statt. Hierbei wurde das Implantat samt umliegendem Gewebe explantiert und histologisch ausgewertet. Neben der Gewichtszunahme wurden die Ratten auf die Bildung von Hernien und intraabdominellen Adh{\"a}sionen sowie auf histologische Ver{\"a}nderungen untersucht. Von n=34 Ratten verstarben n=9 aus unterschiedlichen Gr{\"u}nden. Alle explantierten Wistar Furth Ratten (n=25) zeigten im dreiw{\"o}chigen postoperativen Verlauf (Δt=3 Wochen) physiologische Gewichtskurven. Alle Ratten mit Polymer-Implantat entwickelten im dreiw{\"o}chigen Verlauf eine abdominelle Hernie sowie Adh{\"a}sionen. Eine Zellinfiltration und Gef{\"a}ßeinsprossung im Sinne einer Neovaskularisation konnte nicht nachgewiesen werden. Die histologische Auswertung ergab eine bindegewebige Ver{\"a}nderung im angren-zenden Gewebe, die zusammen mit der immunhistochemisch gesicherten hohen Anzahl an CD68 positiven Zellen (Makrophagen) einer Immunreaktion {\"u}ber den TH1-Pathway entspricht. Bei fehlender Integration in das Gewebe, kommt dies einer Implantatabstoßung gleich. In den Tieren mit Lyoplant® konnten wir die Ergebnisse von Meyer et al. best{\"a}tigen. Zusammenfassend ist zu sagen, dass die bipolaren Polymermembranen viele Eigenschaften eines idealen biokompatiblen Materials erf{\"u}llen, jedoch aufgrund der fehlenden mechanischen Stabilit{\"a}t nicht zur Therapie von kongenitalen Bauchwanddefekten geeignet sind. Lyoplant® hingegen erwies sich in Bezug auf fehlende Hernienbildung und Adh{\"a}sionen, Gef{\"a}ßeinsprossung und Trans-plantatakzeptanz im Vergleich zu den Polymeren als {\"a}ußerst gut geeignetes Material. Um das operative Ergebnis weiter zu perfektionieren, k{\"o}nnte die Besiedelung des Kollagen-Meshs mit Stammzellen experimentell getestet werden. Inwieweit Lyoplant® dann f{\"u}r die Therapie der kongenitalen Bauchwanddefekte geeignet ist, m{\"u}ssen weitere klinische Studien zeigen.},
  subject      = {Bauchwand},
  language  = {de}
}
@article{BoehmTorsinTintetal.2017,
  author    = {B{\"o}hm, Lena and Torsin, Sanda and Tint, Su Hlaing and Eckstein, Marie Therese and Ludwig, Tobias and P{\´e}rez, J. Christian},
  title     = {The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice},
  series = {PLoS Pathogens},
  volume    = {13},
  journal   = {PLoS Pathogens},
  number    = {10},
  doi       = {10.1371/journal.ppat.1006699},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159120},
  pages     = {e1006699},
  year      = {2017},
  abstract  = {Many microorganisms that cause systemic, life-threatening infections in humans reside as harmless commensals in our digestive tract. Yet little is known about the biology of these microbes in the gut. Here, we visualize the interface between the human commensal and pathogenic fungus Candida albicans and the intestine of mice, a surrogate host. Because the indigenous mouse microbiota restricts C. albicans settlement, we compared the patterns of colonization in the gut of germ free and antibiotic-treated conventionally raised mice. In contrast to the heterogeneous morphologies found in the latter, we establish that in germ free animals the fungus almost uniformly adopts the yeast cell form, a proxy of its commensal state. By screening a collection of C. albicans transcription regulator deletion mutants in gnotobiotic mice, we identify several genes previously unknown to contribute to in vivo fitness. We investigate three of these regulators—ZCF8, ZFU2 and TRY4—and show that indeed they favor the yeast form over other morphologies. Consistent with this finding, we demonstrate that genetically inducing non-yeast cell morphologies is detrimental to the fitness of C. albicans in the gut. Furthermore, the identified regulators promote adherence of the fungus to a surface covered with mucin and to mucus-producing intestinal epithelial cells. In agreement with this result, histology sections indicate that C. albicans dwells in the murine gut in close proximity to the mucus layer. Thus, our findings reveal a set of regulators that endows C. albicans with the ability to endure in the intestine through multiple mechanisms.},
  language  = {en}
}
@phdthesis{BuechsenschuetzGoebeler2017,
  author    = {B{\"u}chsensch{\"u}tz-G{\"o}beler, Annekathrin},
  title     = {Parodontitis und kardiovaskul{\"a}re Erkrankungen - Einfluss der Ver{\"a}nderung des subgingivalen Mikrobioms nach systematischer Parodontaltherapie auf Parameter der arteriellen Gef{\"a}ßsteifigkeit},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154415},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Es l{\"a}sst sich feststellen, dass in der vorliegenden Untersuchung eine nichtchirurgische systemische Parodontaltherapie mit und ohne adjuvante Antibiose die beobachteten Keimzahlen der parodontitisassoziierten Keime Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis und Tannerella forsythia signifikant reduzieren konnte. Es konnte jedoch kein direkter Zusammenhang zwischen der beobachteten Keimreduktion des subgingivalen Mikrobioms und der Ver{\"a}nderung der erfassten Parameter der arteriellen Gef{\"a}ßsteifigkeit festgestellt werden. Weitere Interventionsstudien mit h{\"o}heren Patientenzahlen und einer hierdurch m{\"o}glichen differenzierteren Subanalyse des Patientenguts bez{\"u}glich Risikofaktoren wie Tabakkonsum, Medikation oder Lebensalter, sowie der Unterscheidung zwischen aggressiver und chronischer Parodontitis sind erforderlich, um die m{\"o}gliche Existenz eines kausalen Zusammenhangs beider Erkrankungen definitiv abkl{\"a}ren zu k{\"o}nnen.},
  subject      = {Parodontitis},
  language  = {de}
}
@phdthesis{Buentemeyer2017,
  author    = {B{\"u}ntemeyer, Tjark-Ole},
  title     = {Wertigkeit der Leberresektion bei Metastasen des Nebennierenkarzinoms - Analyse anhand des Deutschen Nebennierenkarzinom-Registers},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155743},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Patienten mit einem hepatisch metastasierten Nebennierenkarzinom und ohne Hinweise auf extrahepatische Tumormanifestationen profitieren von einer Operation im Hinblick auf das Gesamt{\"u}berleben. Dies gilt sowohl f{\"u}r synchron- als auch f{\"u}r metachron metastasierte Patienten.},
  subject      = {Nebenniere},
  language  = {de}
}
@article{CaiElMerahbiLoeffleretal.2017,
  author    = {Cai, Kai and El-Merahbi, Rabih and Loeffler, Mona and Mayer, Alexander E. and Sumara, Grzegorz},
  title     = {Ndrg1 promotes adipocyte differentiation and sustains their function},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  number    = {7191},
  doi       = {10.1038/s41598-017-07497-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170565},
  year      = {2017},
  abstract  = {Adipocytes play a central role in maintaining metabolic homeostasis in the body. Differentiation of adipocyte precursor cells requires the transcriptional activity of peroxisome proliferator-activated receptor-γ (Pparγ) and CCAAT/enhancer binding proteins (C/Ebps). Transcriptional activity is regulated by signaling modules activated by a plethora of hormones and nutrients. Mechanistic target of rapamacin complexes (mTORC) 1 and 2 are central for the coordination of hormonal and nutritional inputs in cells and are essential for adipogenesis. Serum glucocorticoid kinase 1 (Sgk1)-dependent phosphorylation of N-Myc downstream-regulated gene 1 (Ndrg1) is a hallmark of mTORC2 activation in cells. Moreover, Pparγ activation promotes Ndrg1 expression. However, the impact of Ndrg1 on adipocyte differentiation and function has not yet been defined. Here, we show that Ndrg1 expression and its Sgk1-dependent phosphorylation are induced during adipogenesis. Consistently, we demonstrate that Ndrg1 promotes adipocyte differentiation and function by inducing Pparγ expression. Additionally, our results indicate that Ndrg1 is required for C/Ebpα phosphorylation. Moreover, we found that Ndrg1 phosphorylation by Sgk1 promotes adipocyte formation. Taken together, we show that induction of Ndrg1 expression by Pparγ and its phosphorylation by Sgk1 kinase are required for the acquisition of adipocyte characteristics by precursor cells.},
  language  = {en}
}
@phdthesis{Carinci2017,
  author    = {Carinci, Flavio},
  title     = {Quantitative Characterization of Lung Tissue Using Proton MRI},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151189},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {The focus of the work concerned the development of a series of MRI techniques that were specifically designed and optimized to obtain quantitative and spatially resolved information about characteristic parameters of the lung. Three image acquisition techniques were developed. Each of them allows to quantify a different parameter of relevant diagnostic interest for the lung, as further described below: 1) The blood volume fraction, which represents the amount of lung water in the intravascular compartment expressed as a fraction of the total lung water. This parameter is related to lung perfusion. 2) The magnetization relaxation time T\(_2\) und T� *\(_2\) , which represents the component of T\(_2\) associated with the diffusion of water molecules through the internal magnetic field gradients of the lung. Because the amplitude of these internal gradients is related to the alveolar size, T\(_2\) und T� *\(_2\) can be used to obtain information about the microstructure of the lung. 3) The broadening of the NMR spectral line of the lung. This parameter depends on lung inflation and on the concentration of oxygen in the alveoli. For this reason, the spectral line broadening can be regarded as a fingerprint for lung inflation; furthermore, in combination with oxygen enhancement, it provides a measure for lung ventilation.},
  subject      = {Kernspintomografie},
  language  = {en}
}
@article{CernaVelazcoFaberJonesPerezetal.2017,
  author    = {Cerna-Velazco, Nhell and Faber, Thomas and Jones-P{\´e}rez, Joel and Porod, Werner},
  title     = {Constraining sleptons at the LHC in a supersymmetric low-scale seesaw scenario},
  series = {European Physical Journal C},
  volume    = {77},
  journal   = {European Physical Journal C},
  doi       = {10.1140/epjc/s10052-017-5231-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173809},
  year      = {2017},
  abstract  = {We consider a scenario inspired by natural supersymmetry, where neutrino data is explained within a low-scale seesaw scenario. We extend the Minimal Supersymmetric Standard Model by adding light right-handed neutrinos and their superpartners, the R-sneutrinos, and consider the lightest neutralinos to be higgsino-like. We consider the possibilities of having either an R-sneutrino or a higgsino as lightest supersymmetric particle. Assuming that squarks and gauginos are heavy, we systematically evaluate the bounds on slepton masses due to existing LHC data.},
  language  = {en}
}
@article{ChenMishraGlaessetal.2017,
  author    = {Chen, Yi-chun and Mishra, Dushyant and Gl{\"a}ß, Sebastian and Gerber, Bertram},
  title     = {Behavioral Evidence for Enhanced Processing of the Minor Component of Binary Odor Mixtures in Larval Drosophila},
  series = {Frontiers in Psychology},
  volume    = {8},
  journal   = {Frontiers in Psychology},
  number    = {1923},
  doi       = {10.3389/fpsyg.2017.01923},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170011},
  year      = {2017},
  abstract  = {A fundamental problem in deciding between mutually exclusive options is that the decision needs to be categorical although the properties of the options often differ but in grade. We developed an experimental handle to study this aspect of behavior organization. Larval Drosophila were trained such that in one set of animals odor A was rewarded, but odor B was not (A+/B), whereas a second set of animals was trained reciprocally (A/B+). We then measured the preference of the larvae either for A, or for B, or for "morphed" mixtures of A and B, that is for mixtures differing in the ratio of the two components. As expected, the larvae showed higher preference when only the previously rewarded odor was presented than when only the previously unrewarded odor was presented. For mixtures of A and B that differed in the ratio of the two components, the major component dominated preference behavior—but it dominated less than expected from a linear relationship between mixture ratio and preference behavior. This suggests that a minor component can have an enhanced impact in a mixture, relative to such a linear expectation. The current paradigm may prove useful in understanding how nervous systems generate discrete outputs in the face of inputs that differ only gradually.},
  language  = {en}
}
@phdthesis{Cheng2017,
  author    = {Cheng, Cheng},
  title     = {Metabolomics and dereplication-based isolation of novel bioactive natural products from marine sponge-associated actinomycetes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136587},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Marine sponge-associated actinomycetes are considered as promising source for the discovery of novel biologically active compounds. Metabolomics coupled multivariate analysis can efficiently reduce the chemical redundancy of re-isolating known compounds at the very early stage of natural product discovery. This Ph.D. project aimed to isolate biologically active secondary metabolites from actinomycetes associated with different Mediterranean sponges with the assistance of metabolomics tools to implement a rapid dereplication and chemically distinct candidate targeting for further up-scaling compounds isolation. This study first focused on the recovery of actinomycetes from marine sponges by various cultivation efforts. Twelve different media and two separate pre-treatments of each bacterial extract were designed and applied to facilitate actinomycete diversity and richness. A total of 64 actinomycetes were isolated from 12 different marine sponge species. The isolates were affiliated to 23 genera representing 8 different suborders based on nearly full-length 16S rRNA gene sequencing. Four putatively novel species belonging to the genera Geodermatophilus, Microlunatus, Rhodococcus, and Actinomycetospora were identified based on a sequence similarity <98.5\% to validly described 16S rRNA gene sequences. 20\% of the isolated actinomycetes was shown to exhibit diverse biological properties, including antioxidant, anti-Bacillus sp., anti-Aspergillus sp., and antitrypanosomal activities. The metabolomics approaches combined with the bioassay results identified two candidate strains Streptomyces sp. SBT348 and Streptomyces sp. SBT345 for further up-scaling cultivation and compounds isolation. Four compounds were isolated from Streptomyces sp. SBT348. Three of these compounds including the new cyclic dipeptide petrocidin A were previously highlighted in the metabolomics analyses, corroborating the feasibility of metabolomics approaches in novel compounds discovery. These four compounds were also tested against two pathogen microorganisms since the same activities were shown in their crude extract in the preliminary bioassay screening, however none of them displayed the expected activities, which may ascribe to the insufficient amount obtained. Streptomyces sp. SBT345 yielded 5 secondary metabolites, three of which were identified as new natural products, namely strepthonium A, ageloline A and strepoxazine A. Strepthonium A inhibited the production of Shiga toxin produced by enterohemorrhagic Escherichia coli at a concentration of 80 μM, without interfering with the bacterial growth. Ageloline A exhibited antioxidant activity and inhibited the inclusion of Chlamydia trachomatis with an IC50 value of 9.54 ± 0.36 μM. Strepoxazine A displayed antiproliferative property towards human promyelocytic HL-60 cells with an IC50 value of 16 μg/ml. 11 These results highlighted marine sponges as a rich source for novel actinomycetes and further exhibited the significance of marine sponge-associated actinomycetes as promising producers of novel biologically active compounds. The chemometrics coupled metabolomics approach also demonstrated its feasibility and efficacy in natural product discovery.},
  subject      = {Actinomyces},
  language  = {en}
}
@article{ChengOthmanStopperetal.2017,
  author    = {Cheng, Cheng and Othman, Eman M. and Stopper, Helga and Edrada-Ebel, RuAngelie and Hentschel, Ute and Abdelmohsen, Usama Ramadan},
  title     = {Isolation of petrocidin A, a new cytotoxic cyclic dipeptide from the marine sponge-derived bacterium \(Streptomyces\) sp. SBT348},
  series = {Marine Drugs},
  volume    = {15},
  journal   = {Marine Drugs},
  number    = {12},
  doi       = {10.3390/md15120383},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172644},
  year      = {2017},
  abstract  = {A new cyclic dipeptide, petrocidin A (\(\textbf{1}\)), along with three known compounds—2,3-dihydroxybenzoic acid (\(\textbf{2}\)), 2,3-dihydroxybenzamide (\(\textbf{3}\)), and maltol (\(\textbf{4}\))—were isolated from the solid culture of \(Streptomyces\) sp. SBT348. The strain \(Streptomyces\) sp. SBT348 had been prioritized in a strain collection of 64 sponge-associated actinomycetes based on its distinct metabolomic profile using liquid chromatography/high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). The absolute configuration of all α-amino acids was determined by HPLC analysis after derivatization with Marfey's reagent and comparison with commercially available reference amino acids. Structure elucidation was pursued in the presented study by mass spectrometry and NMR spectral data. Petrocidin A (\(\textbf{1}\)) and 2,3-dihydroxybenzamide (\(\textbf{3}\)) exhibited significant cytotoxicity towards the human promyelocytic HL-60 and the human colon adenocarcinoma HT-29 cell lines. These results demonstrated the potential of sponge-associated actinomycetes for the discovery of novel and pharmacologically active natural products.},
  language  = {en}
}
@phdthesis{Cherpokova2017,
  author    = {Cherpokova, Deya},
  title     = {Studies on modulators of platelet (hem)ITAM signaling and platelet production in genetically modified mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120068},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Summary Platelet activation and aggregation at sites of vascular injury is critical to prevent excessive blood loss, but may also lead to life-threatening ischemic disease states, such as myocardial infarction and stroke. Glycoprotein (GP) VI and C type lectin-like receptor 2 (CLEC-2) are essential platelet activating receptors in hemostasis and thrombo-inflammatory disease which signal through a (hem)immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway. The adapter molecules Src-like adapter protein (SLAP) and SLAP2 are involved in the regulation of immune cell receptor surface expression and signaling, but their function in platelets is unknown. As revealed in this thesis, single deficiency of SLAP or SLAP2 in mice had only moderate effects on platelet function, while SLAP/SLAP2 double deficiency resulted in markedly increased signal transduction, integrin activation, granule release, aggregation, procoagulant activity and thrombin generation following (hem)ITAM-coupled, but not G protein-coupled receptor activation. Slap-/-/Slap2-/- mice displayed accelerated occlusive arterial thrombus formation and a dramatically worsened outcome after focal cerebral ischemia. These results establish SLAP and SLAP2 as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke. GPVI has emerged as a promising novel pharmacological target for treatment of thrombotic and inflammatory disease states, but the exact mechanisms of its immunodepletion in vivo are incompletely understood. It was hypothesized that SLAP and SLAP2 may be involved in the control of GPVI down-regulation because of their role in the internalization of immune cell receptors. As demonstrated in the second part of the thesis, SLAP and SLAP2 were dispensable for antibody-induced GPVI down-regulation, but anti-GPVI treatment resulted in prolonged strong thrombocytopenia in Slap-/-/Slap2-/- mice. The profound thrombocytopenia likely resulted from the powerful platelet activation which the anti-GPVI antibody induced in Slap-/-/Slap2-/- platelets, but importantly, not in wild-type platelets. These data indicate that the expression and activation state of key modulators of the GPVI signaling cascade may have important implications for the safety profile and efficacy of anti-GPVI agents. Small GTPases of the Rho family, such as RhoA and Cdc42, are critically involved in the regulation of cytoskeletal rearrangements during platelet activation, but little is known about the specific roles and functional redundancy of both proteins in platelet biogenesis. As shown in the final part of the thesis, combined deficiency of RhoA and Cdc42 led to marked alterations in megakaryocyte morphology and the generation of platelets of heterogeneous size and granule content. Despite severe hemostatic defects and profound thrombo¬cytopenia, circulating RhoA-/-/Cdc42-/- platelets were still capable of granule secretion and the formation of occlusive thrombi. These results implicate the existence of both distinct and overlapping roles of RhoA and Cdc42 in platelet production and function.},
  subject      = {Thrombozyt},
  language  = {en}
}
@article{ChiesaGreinerSchoenherretal.2017,
  author    = {Chiesa, Mauro and Greiner, Nicolas and Sch{\"o}nherr, Marek and Tramontano, Francesco},
  title     = {Electroweak corrections to diphoton plus jets},
  series = {Journal of High Energy Physics},
  journal   = {Journal of High Energy Physics},
  number    = {10},
  doi       = {10.1007/JHEP10(2017)181},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173512},
  year      = {2017},
  abstract  = {We calculate the next-to-leading order electroweak corrections to the production of a photon pair in association with zero, one and two jets at the LHC. We use GoSam and Sherpa to obtain the results in a fully automated way. For a typical set of fiducial cuts the electroweak corrections lead to a modification of the total cross section of up to 3\%, depending on the jet multiplicity. We find substantial contributions in differential distributions, leading to tens of per cent corrections for phase space regions within the reach of the LHC. Furthermore we investigate the importance of photon induced processes as well as subleading contributions. Photon induced processes are found to be negligible, subleading contributions can have a sizeable impact however they can be removed by appropriate phase space cuts.},
  language  = {en}
}
@phdthesis{Chikezie2017,
  author    = {Chikezie, Aloysius Cheta},
  title     = {THE VALUE OF WORK IN NIGERIA with Reference to Laborem Exercens},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147592},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Work is seen by many thinkers as the fundamental dimension of man`s existence on earth. Through work, he provides his basic necessities on earth and co-operate with God in the work of creation. He received this mandate to work from the very beginning of creation by God. In carrying out this mandate, man every human being reflects the very action of the creator of the Universe. God worked and intended that man who is created in His image and likeness continues the work of creation by working. Even though Man suffers and sweats through work and yet, in spite of all this toil-perhaps in a sense because of it - work is a good thing for man. It is not only good in the sense that it is useful or something to enjoy; it is also good as being something worthy, that is to say something that corresponds to man's dignity that expresses this dignity and increases it. This project examines man as a creature called to work and born into work. It is true that through work, man provides himself and his family with the basic necessities of life and everyday needs for the reason he charges wages for his sweat. Work goes beyond and should exceed the boundaries of the material benefit that comes out of it to the satisfaction and fulfilment for the very purpose we should work. The modern society has attached so much importance to money and material possession, the question then is how do we go along working in the spirit of improvement and renewal of the earth? The modern man understands work only as a means of making his daily bread. For this reason, he engages himself in an occupation that he has little or no interest in. He ends up quarrelling everyday with the people that he or she is supposed to serve through work. The result is low work output and waste of talents and the society loses an opportunity for improvement as every creature is supposed to contribute uniquely. A good example is Nigeria, Africa's most populous nation with a population estimate of about over 170,000,000 people and the sixth Oil producing Nation.},
  subject      = {Nigeria},
  language  = {en}
}
@phdthesis{Chouhan2017,
  author    = {Chouhan, Nitin Singh},
  title     = {Time-odor learning in \(Drosophila\) \(melanogaster\)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145675},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Endogenous clocks help animals to anticipate the daily environmental changes. These internal clocks rely on environmental cues, called Zeitgeber, for synchronization. The molecular clock consists of transcription-translation feedback loops and is located in about 150 neurons (Helfrich-F{\"o}rster and Homberg, 1993; Helfrich-F{\"o}rster, 2005). The core clock has the proteins Clock (CLK) and Cycle (CYC) that together act as a transcription activator for period (per) and timeless (tim) which then, via PER and TIM block their own transcription by inhibiting CLK/CYC activity (Darlington et al., 1998; Hardin, 2005; Dubruille and Emery, 2008). Light signals trigger the degradation of TIM through a blue-light sensing protein Cryptochrome (CRY) and thus, allows CLK/CYC to resume per and tim transcription (Emery et al., 1998; Stanewsky et al., 1998). Therefore, light acts as an important Zeitgeber for the clock entrainment. The mammalian clock consists of similarly intertwined feedback loops. Endogenous clocks facilitate appropriate alterations in a variety of behaviors according to the time of day. Also, these clocks can provide the phase information to the memory centers of the brain to form the time of day related associations (TOD). TOD memories promote appropriate usage of resources and concurrently better the survival success of an animal. For instance, animals can form time-place associations related to the availability of a biologically significant stimulus like food or mate. Such memories will help the animal to obtain resources at different locations at the appropriate time of day. The significance of these memories is supported by the fact that many organisms including bees, ants, rats and mice demonstrate time-place learning (Biebach et al. 1991; Mistlberger et al. 1997; Van der Zee et al. 2008; Wenger et al. 1991). Previous studies have shown that TOD related memories rely on an internal clock, but the identity of the clock and the underlying mechanism remain less well understood. The present study demonstrates that flies can also form TOD associated odor memories and further seeks to identify the appropriate mechanism. Hungry flies were trained in the morning to associate odor A with the sucrose reward and subsequently were exposed to odor B without reward. The same flies were exposed in the afternoon to odor B with and odor A without reward. Two cycles of the 65 reversal training on two subsequent days resulted in the significant retrieval of specific odor memories in the morning and afternoon tests. Therefore, flies were able to modulate their odor preference according to the time of day. In contrast, flies trained in a non-reversal manner were unable to form TOD related memories. The study also demonstrates that flies are only able to form time-odor memories when the two reciprocal training cycles occur at a minimum 6 h interval. This work also highlights the role of the internal state of flies in establishing timeodor memories. Prolonged starvation motivates flies to appropriate their search for the food. It increases the cost associated with a wrong choice in the T-maze test as it precludes the food discovery. Accordingly, an extended starvation promotes the TOD related changes in the odor preference in flies already with a single cycle of reversal training. Intriguingly, prolonged starvation is required for the time-odor memory acquisition but is dispensable during the memory retrieval. Endogenous oscillators promote time-odor associations in flies. Flies in constant darkness have functional rhythms and can form time-odor memories. In contrast, flies kept in constant light become arrhythmic and demonstrated no change in their odor preference through the day. Also, clock mutant flies per01 and clkAR, show compromised performance compared to CS flies when trained in the time-odor conditioning assay. These results suggest that flies need a per and clk dependent oscillator for establishing TOD related memories. Also, the clock governed rhythms are necessary for the timeodor memory acquisition but not for the retrieval. Pigment-Dispersing Factor (PDF) neuropeptide is a clock output factor (Park and Hall, 1998; Park et al., 2000; Helfrich-F{\"o}rster, 2009). pdf01 mutant flies are unable to form significant time-odor memories. PDF is released by 8 neurons per hemisphere in the fly brain. This cluster includes the small (s-LNvs) and large (l-LNvs) ventral lateral neurons. Restoring PDF in these 16 neurons in the pdf01 mutant background rescues the time-odor learning defect. The PDF neuropeptide activates a seven transmembrane G-protein coupled receptor (PDFR) which is broadly expressed in the fly brain (Hyun et al., 2005). The present study shows that the expression of PDFR in about 10 dorsal neurons (DN1p) is sufficient for robust time-odor associations in flies. 66 In conclusion, flies use distinct endogenous oscillators to acquire and retrieve time-odor memories. The first oscillator is light dependent and likely signals through the PDF neuropeptide to promote the usage of the time as an associative cue during appetitive conditioning. In contrast, the second clock is light independent and specifically signals the time information for the memory retrieval. The identity of this clock and the underlying mechanism are open to investigation.},
  subject      = {Taufliege},
  language  = {en}
}
@article{CollenburgBeyersdorfWieseetal.2017,
  author    = {Collenburg, Lena and Beyersdorf, Niklas and Wiese, Teresa and Arenz, Christoph and Saied, Essa M. and Becker-Flegler, Katrin Anne and Schneider-Schaulies, Sibylle and Avota, Elita},
  title     = {The activity of the neutral sphingomyelinase is important in T cell recruitment and directional migration},
  series = {Frontiers in Immunology},
  volume    = {8},
  journal   = {Frontiers in Immunology},
  number    = {1007},
  doi       = {10.3389/fimmu.2017.01007},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158944},
  year      = {2017},
  abstract  = {Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM) has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization. Because these are important parameters in directional T cell migration and motility in tissues, we analyzed the role of the NSM in these processes. Pharmacological inhibition of NSM interfered with early lymph node homing of T cells in vivo indicating that the enzyme impacts on endothelial adhesion, transendothelial migration, sensing of chemokine gradients or, at a cellular level, acquisition of a polarized phenotype. NSM inhibition reduced adhesion of T cells to TNF-α/IFN-γ activated, but not resting endothelial cells, most likely via inhibiting high-affinity LFA-1 clustering. NSM activity proved to be highly important in directional T cell motility in response to SDF1-α, indicating that their ability to sense and translate chemokine gradients might be NSM dependent. In fact, pharmacological or genetic NSM ablation interfered with T cell polarization both at an overall morphological level and redistribution of CXCR4 and pERM proteins on endothelial cells or fibronectin, as well as with F-actin polymerization in response to SDF1-α stimulation, indicating that efficient directional perception and signaling relay depend on NSM activity. Altogether, these data support a central role of the NSM in T cell recruitment and migration both under homeostatic and inflamed conditions by regulating polarized redistribution of receptors and their coupling to the cytoskeleton.},
  language  = {en}
}
@phdthesis{ContarAdolfi2017,
  author    = {Contar Adolfi, Mateus},
  title     = {Sex determination and meiosis in medaka: The role of retinoic acid},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136335},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Sex determination (SD) is a complex and diverse developmental process that leads to the decision whether the bipotential gonad anlage will become a testis or an ovary. This mechanism is regulated by gene cascades, networks and/or chromosomal systems, and can be influenced by fluctuations of extrinsic factors like temperature, exposure to hormones and pollution. Within vertebrates, the group of fish show the widest variety of sex determination mechanism. This whole diversity of processes and mechanisms converges to the formation of two different gametes, the eggs and the sperm, the first bigger and static, and the second smaller and motile. Meiosis is crucial for the formation of both types of gametes, and the timing of meiosis entry is one of the first recognizable differences between male and female in vertebrates. The germ cells go into meiosis first in female than in male, and in mammals, this event has been shown to be regulated by retinoic acid (RA). This small polar molecule induces in the germ cells the expression of the pre-meiotic marker Stra8 (stimulated by retinoic acid gene 8), which is necessary for meiosis initiation. Interestingly, genome analyzes have shown that the majority of fish (including medaka) lack the stra8 gene, adding a question mark to the role of RA in meiosis induction in this group. Since a role of RA in entry of meiosis and sexual development of fish is still far from being understood, I investigated in medaka (Oryzias latipes) a possible signaling function of RA during the SD period in embryos and in reproductively active gonads of adults. I generated a transgenic medaka line that reports responsiveness to RA in vivo. With this tool, I compared RA responsiveness with the expression of the main gene involved in the synthesis of RA. My results show that there is a de-correlation between the action of RA with its source. In adults, expression of the RA metabolizing enzymes show sexually dimorphic RA levels, with aldh1a2 levels being higher in testis, and cyp26a1 stronger in female gonad. In ovary, the responsiveness is restricted to the early meiotic oocytes. In testis, RA is acting directly in the pre-meiotic cells, but also in Sertoli and Leydig cells. Treatment experiments on testis organ culture showed that RA pathway activation leads to a decrease in meiosis markers expression levels. During the development, RA responsiveness in the germ cells was observed in both sexes much earlier than the first female meiosis entry. Treatments with RA-synthesis inhibitor show a decrease in meiosis markers expression levels only after the sex differentiation period in female. Expression analyzes of embryos treated with exogenous RA showed induction of dmrt1a at the gonad levels and an increase of amh levels. Both genes are not only involved in male formation, but also in the regulation of germ cell proliferation and differentiation. RA is important in meiosis induction and gametogenesis in adult medaka. However, there is no evidence for a similar role of RA in initiating the first meiosis in female germ cells at the SD stage. Moreover, contrary to common expectation, RA seems to induce sex related genes that are involved indirectly in meiosis inhibition. In this thesis, I showed for the first time that RA can be involved in both induction and inhibition of meiosis entry, depending on the sex and the developmental stage in a stra8-independent model organism.},
  subject      = {Japank{\"a}rpfling},
  language  = {en}
}
@article{CosteaCoelhoSunagawaetal.2017,
  author    = {Costea, Paul I. and Coelho, Louis Pedro and Sunagawa, Shinichi and Munch, Robin and Huerta-Cepas, Jaime and Forslund, Kristoffer and Hildebrand, Falk and Kushugulova, Almagul and Zeller, Georg and Bork, Peer},
  title     = {Subspecies in the global human gut microbiome},
  series = {Molecular Systems Biology},
  volume    = {13},
  journal   = {Molecular Systems Biology},
  number    = {12},
  doi       = {10.15252/msb.20177589},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172674},
  year      = {2017},
  abstract  = {Population genomics of prokaryotes has been studied in depth in only a small number of primarily pathogenic bacteria, as genome sequences of isolates of diverse origin are lacking for most species. Here, we conducted a large-scale survey of population structure in prevalent human gut microbial species, sampled from their natural environment, with a culture-independent metagenomic approach. We examined the variation landscape of 71 species in 2,144 human fecal metagenomes and found that in 44 of these, accounting for 72\% of the total assigned microbial abundance, single-nucleotide variation clearly indicates the existence of sub-populations (here termed subspecies). A single subspecies (per species) usually dominates within each host, as expected from ecological theory. At the global scale, geographic distributions of subspecies differ between phyla, with Firmicutes subspecies being significantly more geographically restricted. To investigate the functional significance of the delineated subspecies, we identified genes that consistently distinguish them in a manner that is independent of reference genomes. We further associated these subspecies-specific genes with properties of the microbial community and the host. For example, two of the three Eubacterium rectale subspecies consistently harbor an accessory pro-inflammatory flagellum operon that is associated with lower gut community diversity, higher host BMI, and higher blood fasting insulin levels. Using an additional 676 human oral samples, we further demonstrate the existence of niche specialized subspecies in the different parts of the oral cavity. Taken together, we provide evidence for subspecies in the majority of abundant gut prokaryotes, leading to a better functional and ecological understanding of the human gut microbiome in conjunction with its host.},
  language  = {en}
}
@article{DaineseSchneiderKraussetal.2017,
  author    = {Dainese, Matteo and Schneider, Gudrun and Krauss, Jochen and Steffan-Dewenter, Ingolf},
  title     = {Complementarity among natural enemies enhances pest suppression},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-017-08316-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158621},
  pages     = {8172},
  year      = {2017},
  abstract  = {Natural enemies have been shown to be effective agents for controlling insect pests in crops. However, it remains unclear how different natural enemy guilds contribute to the regulation of pests and how this might be modulated by landscape context. In a field exclusion experiment in oilseed rape (OSR), we found that parasitoids and ground-dwelling predators acted in a complementary way to suppress pollen beetles, suggesting that pest control by multiple enemies attacking a pest during different periods of its occurrence in the field improves biological control efficacy. The density of pollen beetle significantly decreased with an increased proportion of non-crop habitats in the landscape. Parasitism had a strong effect on pollen beetle numbers in landscapes with a low or intermediate proportion of non-crop habitats, but not in complex landscapes. Our results underline the importance of different natural enemy guilds to pest regulation in crops, and demonstrate how biological control can be strengthened by complementarity among natural enemies. The optimization of natural pest control by adoption of specific management practices at local and landscape scales, such as establishing non-crop areas, low-impact tillage, and temporal crop rotation, could significantly reduce dependence on pesticides and foster yield stability through ecological intensification in agriculture.},
  language  = {en}
}
@phdthesis{Danner2017,
  author    = {Danner, Nadja},
  title     = {Honey bee foraging in agricultural landscapes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139322},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {1. Today honey bee colonies face a wide range of challenges in modern agricultural landscapes which entails the need for a comprehensive investigation of honey bees in a landscape context and the assessment of environmental risks. Within this dissertation the pollen foraging of honey bee colonies is studied in different agricultural landscapes to gain insight into the use of pollen resources and the influence of landscape structure across the season. General suggestions for landscape management to support honey bees and other pollinators are derived. 2. Decoding of waggle dances and a subsequent spatial foraging analysis are used as methods in Chapters 4 and 5 to study honey bee colonies in agricultural landscapes. The recently developed metabarcoding of mixed pollen samples was applied for the first time in honey bee foraging ecology and allowed for a detailed analysis of pollen, that was trapped from honey bees in front hive entrances (Chapter 6). 3. Pollen identification through molecular sequencing and DNA barcoding has been proposed as an alternative approach to light microscopy, which still is a tedious and error-prone task. In this study we assessed mixed pollen probes through next-generation sequencing and developed a bioinformatic workflow to analyse these high-throughput data with a newly created reference database. To evaluate the feasibility, we compared results from classical identification based on light microscopy from the same samples with our sequencing results. Abundance estimations from sequencing data were significantly correlated with counted abundances through light microscopy. Next-generation sequencing thus presents a useful and efficient workflow to identify pollen at the genus and species level without requiring specialized palynological expert knowledge. 4. During maize flowering, four observation hives were placed in and rotated between 11 landscapes covering a gradient in maize acreage. A higher foraging frequency on maize fields compared to other landuse types showed that maize is an intensively used pollen resource for honey bee colonies. Mean foraging distances were significantly shorter for maize pollen than for other pollen origins, indicating that effort is put into collecting a diverse pollen diet. The percentage of maize pollen foragers did not increase with maize acreage in the landscape and was not reduced by grassland area as an alternative pollen resource. Our findings allow estimating the distance-related exposure risk of honey bee colonies to pollen from surrounding maize fields treated with systemic insecticides. 5. It is unknown how an increasing area of mass-flowering crops like oilseed rape (OSR) or a decrease of semi-natural habitats (SNH) change the temporal and spatial availability of pollen resources for honey bee colonies, and thus foraging distances and frequency in different habitat types. Sixteen observation hives were placed in and rotated between 16 agricultural landscapes with independent gradients of OSR and SNH area within 2 km to analyze foraging distances and frequencies. SNH and OSR reduced foraging distance at different spatial scales and depending on season, with possible benefits for the performance of honey bee colonies. Frequency of pollen foragers per habitat type was equally high for SNH, grassland and OSR fields, but lower for other crops and forest. In landscapes with a small proportion of SNH a significantly higher density of pollen foragers on SNH was observed, indicating the limitation of pollen resources in simple agricultural landscapes and the importance of SNH. 6. Quantity and diversity of collected pollen can influence the growth and health of honey bee colonies, but little is known about the influence of landscape structure on pollen diet. In a field experiment we rotated 16 honey bee colonies across 16 agricultural landscapes (see also Chapter 5), used traps to get samples of collected pollen and observed the intra-colonial dance communication to gain information about foraging distances. Neither the amount of collected pollen nor pollen diversity were related to landscape diversity. The revealed increase of foraging distances with decreasing landscape diversity suggests that honey bees compensate for a lower landscape diversity by increasing their pollen foraging range in order to maintain pollen amount and diversity. 7. Our results show the importance of diverse pollen resources for honey bee colonies in agricultural landscapes. Beside the risk of exposure to pesticides honey bees face the risk of nutritional deficiency with implications for their health. By modifying landscape composition and therefore availability of resources we are able to contribute to the wellbeing of honey bees. Agri-environmental schemes aiming to support pollinators should focus on possible spatial and temporal gaps in pollen availability and diversity in agricultural landscapes.},
  subject      = {Apis mellifera},
  language  = {en}
}
@article{DannerKellerHaerteletal.2017,
  author    = {Danner, Nadja and Keller, Alexander and H{\"a}rtel, Stephan and Steffan-Dewenter, Ingolf},
  title     = {Honey bee foraging ecology: Season but not landscape diversity shapes the amount and diversity of collected pollen},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0183716},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170424},
  pages     = {e0183716},
  year      = {2017},
  abstract  = {The availability of pollen in agricultural landscapes is essential for the successful growth and reproduction of honey bee colonies (Apis mellifera L.). The quantity and diversity of collected pollen can influence the growth and health of honey bee colonies, but little is known about the influence of landscape structure on pollen diet. In a field experiment, we rotated 16 honey bee colonies across 16 agricultural landscapes, used traps to collect samples of collected pollen and observed intra-colonial dance communication to gain information about foraging distances. DNA metabarcoding was applied to analyze mixed pollen samples. Neither the amount of collected pollen nor pollen diversity was related to landscape diversity. However, we found a strong seasonal variation in the amount and diversity of collected pollen in all sites independent of landscape diversity. The observed increase in foraging distances with decreasing landscape diversity suggests that honey bees compensated for lower landscape diversity by increasing their pollen foraging range in order to maintain pollen amount and diversity. Our results underscore the importance of a diverse pollen diet for honey bee colonies. Agri-environmental schemes aiming to support pollinators should focus on possible spatial and temporal gaps in pollen availability and diversity in agricultural landscapes.},
  language  = {en}
}
@article{DeaconWiedenmannBocquillonetal.2017,
  author    = {Deacon, R. S. and Wiedenmann, J. and Bocquillon, E. and Dom{\´i}nguez, F. and Klapwijk, T. M. and Leubner, P. and Br{\"u}ne, C. and Hankiewicz, E. M. and Tarucha, S. and Ishibashi, K. and Buhmann, H. and Molenkamp, L. W.},
  title     = {Josephson Radiation from Gapless Andreev Bound States in HgTe-Based Topological Junctions},
  series = {Physical Review X},
  volume    = {7},
  journal   = {Physical Review X},
  number    = {021011},
  doi       = {10.1103/PhysRevX.7.021011},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170969},
  year      = {2017},
  abstract  = {Frequency analysis of the rf emission of oscillating Josephson supercurrent is a powerful passive way of probing properties of topological Josephson junctions. In particular, measurements of the Josephson emission enable the detection of topological gapless Andreev bound states that give rise to emission at half the Josephson frequency f\(_{J}\) rather than conventional emission at f\(_{J}\). Here, we report direct measurement of rf emission spectra on Josephson junctions made of HgTe-based gate-tunable topological weak links. The emission spectra exhibit a clear signal at half the Josephson frequency f\(_{J}\)/2. The linewidths of emission lines indicate a coherence time of 0.3-4 ns for the f\(_{J}\)/2 line, much shorter than for the f\(_{J}\) line (3-4 ns). These observations strongly point towards the presence of topological gapless Andreev bound states and pave the way for a future HgTe-based platform for topological quantum computation.},
  language  = {en}
}
@article{DegenHovestadtMitesseretal.2017,
  author    = {Degen, Tobias and Hovestadt, Thomas and Mitesser, Oliver and H{\"o}lker, Franz},
  title     = {Altered sex-specific mortality and female mating success: ecological effects and evolutionary responses},
  series = {Ecosphere},
  volume    = {8},
  journal   = {Ecosphere},
  number    = {5},
  doi       = {10.1002/ecs2.1820},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170953},
  pages     = {e01820},
  year      = {2017},
  abstract  = {Theory predicts that males and females should often join the mating pool at different times (sexual dimorphism in timing of emergence [SDT]) as the degree of SDT affects female mating success. We utilize an analytical model to explore (1) how important SDT is for female mating success, (2) how mating success might change if either sex's mortality (abruptly) increases, and (3) to what degree evolutionary responses in SDT may be able to mitigate the consequences of such mortality increase. Increasing male pre-mating mortality has a non-linear effect on the fraction of females mated: The effect is initially weak, but at some critical level a further increase in male mortality has a stronger effect than a similar increase in female mortality. Such a change is expected to impose selection for reduced SDT. Increasing mortality during the mating season has always a stronger effect on female mating success if the mortality affects the sex that emerges first. This bias results from the fact that enhancing mortality of the earlier emerging sex reduces female-male encounter rates. However, an evolutionary response in SDT may effectively mitigate such consequences. Further, if considered independently for females and males, the predicted evolutionary response in SDT could be quite dissimilar. The difference between female and male evolutionary response in SDT leads to marked differences in the fraction of fertilized females under certain conditions. Our model may provide general guidelines for improving harvesting of populations, conservation management of rare species under altered environmental conditions, or maintaining long-term efficiency of pest-control measures.},
  language  = {en}
}
@phdthesis{Demirhan2017,
  author    = {Demirhan, Attila},
  title     = {Korrelation zwischen blutrheologischen Parametern und Blutk{\"o}rper-Indizes von Erythrozyten bei gesunden Frauen vor elektiven gyn{\"a}kologischen Eingriffen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155633},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Die vorliegende Arbeit quantifiziert die Korrelationen zwischen blutrheologischen Parametern und Erythrozyten-Indizes an einem repr{\"a}sentativen und gut definierten Kollektiv gesunder Frauen im Vorfeld eines elektiven gyn{\"a}kologischen Eingriffes. Gem{\"a}ß der erhobenen Resultate besteht bei 286 gesunden Frauen mittleren Alters zwischen der Verformbarkeit, dem MCV und dem MCH der Erythrozyten eine statistisch signifikante Korrelation, die in Gegenwart hoher Scherkr{\"a}fte an Auspr{\"a}gung zunimmt. Gleichzeitig vermindert sich mit zunehmender MCHC die Erythrozytenverformbarkeit stetig und statistisch signifikant, wobei dieser Effekt am deutlichsten in Gegenwart hoher Scherkr{\"a}fte, wie diese beispielsweise in den Kapillaren der Endstrombahn anzunehmen sind, nachweisbar ist.},
  subject      = {Red cell deformability},
  language  = {de}
}