@article{ŞenOrhanSerteletal.2020,
  author    = {Şen, Sinan and Orhan, G{\"u}l and Sertel, Serkan and Schmitter, Marc and Schindler, Hans J. and Lux, Christopher J. and Giannakopoulos, Nikolaos Nikitas},
  title     = {Comparison of acupuncture on specific and non-specific points for the treatment of painful temporomandibular disorders: A randomised controlled trial},
  series = {Journal of Oral Rehabilitation},
  volume    = {47},
  journal   = {Journal of Oral Rehabilitation},
  number    = {7},
  doi       = {10.1111/joor.12952},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215419},
  pages     = {783 -- 795},
  year      = {2020},
  abstract  = {Background and Objective The aim of this single-centre, two-arm, parallel-group, double-blinded, randomised controlled trial was to investigate the disputed specific effectiveness of acupuncture by comparing acupuncture on specific and non-specific points among patients with non-chronic, painful TMDs. Methods Following predefined eligibility criteria, 49 consecutive patients of both sexes were recruited to the study. All subjects were diagnosed with a non-chronic (Graded Chronic Pain Scale grade <3) painful TMD, as assessed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Patients were randomly assigned to group A (acupuncture on specific points) or group B (acupuncture on non-specific points) after the initial examination (T0). Both acupuncture treatment sessions were conducted by a trained dentist once a week for four weeks. The examination was repeated five weeks (T5) after T0 by one calibrated examiner who was unaware of the study groups. Characteristic pain intensity (CPI) was evaluated as the main outcome criterion and compared between times and treatment groups by means of non-parametric tests (significance level set at P = .05). Secondary outcomes comprised the maximum corrected active mouth-opening without pain (MAO); patients' expectations regarding acupuncture treatment and pain development; depressivity; and oral health-related quality of life (OHRQoL). Results A total of 41 patients (38 female) successfully completed the study (mean age: 40.17 ± 16.61). The two groups did not differ significantly at any time in terms of age and CPI. However, CPI was significantly (P < .05) lower at T5 than at T0 for both groups (29.66 and 30.35\% lower in group A and group B, respectively). An increase in MAO was observed at T5 for both groups but was significant for group B only (P = .016). All patients had positive expectations of acupuncture therapy, and the two groups did not differ significantly at T5 with regard to the extent to which their expectations had been fulfilled by the treatment (P = .717). Comparison of T0 and T5 showed a statistically significant reduction of depressivity for group A (P = .0205), but no significant change for group B (P = .329). At T5, OHRQoL had improved significantly for both groups (group A, P = .018; group B, P < .001) compared with at T0. Conclusions Acupuncture on both specific and non-specific points reduces the non-dysfunctional pain of TMD patients. The effect of acupuncture on painful TMD cannot be attributed to the specific point selection.},
  language  = {en}
}
@article{UeceylerBuchholzKewenigetal.2020,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Buchholz, Hans-Georg and Kewenig, Susanne and Ament, Stephan-Johann and Birklein, Frank and Schreckenberger, Mathias and Sommer, Claudia},
  title     = {Cortical Binding Potential of Opioid Receptors in Patients With Fibromyalgia Syndrome and Reduced Systemic Interleukin-4 Levels - A Pilot Study},
  series = {Frontiers in Neuroscience},
  volume    = {14},
  journal   = {Frontiers in Neuroscience},
  issn      = {1662-453X},
  doi       = {10.3389/fnins.2020.00512},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204457},
  year      = {2020},
  abstract  = {Objective: We investigated cerebral opioid receptor binding potential in patients with fibromyalgia syndrome (FMS) using positron-emission-tomography (PET) and correlated our results with patients' systemic interleukin-4 (IL-4) gene expression. Methods: In this pilot study, seven FMS patients (1 man, 6 women) agreed to participate in experimental PET scans. All patients underwent neurological examination, were investigated with questionnaires for pain, depression, and FMS symptoms. Additionally, blood for IL-4 gene expression analysis was withdrawn at two time points with a median latency of 1.3 years. Patients were investigated in a PET scanner using the opioid receptor ligand F-18-fluoro-ethyl-diprenorphine ([18F]FEDPN) and results were compared with laboratory normative values. Results: Neurological examination was normal in all FMS patients. Reduced opioid receptor binding was found in mid cingulate cortex compared to healthy controls (p < 0.005). Interestingly, three patients with high systemic IL-4 gene expression had increased opioid receptor binding in the fronto-basal cortex compared to those with low IL-4 gene expression (p < 0.005). Conclusion: Our data give further evidence for a reduction in cortical opioid receptor availability in FMS patients as another potential central nervous system contributor to pain in FMS.},
  language  = {en}
}
@article{ZulloFleckensteinSchleipetal.2020,
  author    = {Zullo, Alberto and Fleckenstein, Johannes and Schleip, Robert and Hoppe, Kerstin and Wearing, Scott and Klingler, Werner},
  title     = {Structural and Functional Changes in the Coupling of Fascial Tissue, Skeletal Muscle, and Nerves During Aging},
  series = {Frontiers in Physiology},
  volume    = {11},
  journal   = {Frontiers in Physiology},
  number    = {592},
  issn      = {1664-042X},
  doi       = {10.3389/fphys.2020.00592},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206890},
  year      = {2020},
  abstract  = {Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair.},
  language  = {en}
}
@phdthesis{Zinner2020,
  author    = {Zinner, Martin Gerhard},
  title     = {Adsorbat-induzierte Oberfl{\"a}chensysteme und ultra-d{\"u}nne intermetallische Legierungsfilme im Fokus der niederenergetischen Elektronenbeugung und spektroskopischer Analysemethoden},
  doi       = {10.25972/OPUS-19274},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192749},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Im Rahmen der vorliegenden Dissertation werden mit unterschiedlichen Analysemethoden die Korrelationen zwischen den strukturellen, elektronischen und magnetischen Eigenschaften von Selten Erd-basierten intermetallischen Oberfl{\"a}chenlegierungen anhand der beiden Probensysteme LaPt\$_5\$/Pt(111) und CePt\$_5\$/Pt(111) untersucht. Dar{\"u}ber hinaus werden die strukturellen Eigenschaften von Adsorbat-induzierten Oberfl{\"a}chenrekonstruktionen im sub-ML Bereich in reduzierten Dimensionen auf der Halbleiteroberfl{\"a}che Si(111) anhand der beiden Materialsysteme Si(111)-(5\$\times\$2)-Au und Si(111)-(\$\sqrt{3}\times\sqrt{3}\$)R30\${\degree}\$-Sn mit der Methode LEED-IV analysiert. Das erste experimentelle Kapitel dieser Arbeit behandelt die intermetallische Oberfl{\"a}chenlegierung LaPt\$_5\$/Pt(111), die sich ausbildet wenn La-Atome auf einem sauberen Pt(111)-Substrat abgeschieden werden und anschließend thermische Energie hinzugef{\"u}gt wird. Die Dicke der gebildeten Legierung l{\"a}sst sich {\"u}ber die zuvor angebotene Menge an La-Atomen variieren und resultiert aufgrund der Gitterfehlanpassung von Pt(111) und den obenauf liegenden LaPt\$_5\$-Filmen in sechs unterschiedliche Beugungsmuster im LEED, deren {\"U}berstrukturvektoren durch zwei unterschiedliche Rotationsausrichtungen in Bezug auf das Gitter des Substrats und unterschiedlichen lateralen Gitterkonstanten der Filme gekennzeichnet sind. Die atomare Struktur kann auf eine gemeinsame Kristallstruktur zur{\"u}ckgef{\"u}hrt werden, deren St{\"o}chiometrie aus dickenabh{\"a}ngigen AES-Messungen zu LaPt\$_5\$ mit einer Pt-reichen Oberfl{\"a}chenabschlusslage bestimmt werden konnte. Die Ergebnisse einer durchgef{\"u}hrten LEED-IV Studie best{\"a}tigen das Wachstum der Filme in der CaCu\$_5\$-Struktur, wobei die Oberfl{\"a}chenterminierungslage im Vergleich zum Volumengitter ein zus{\"a}tzliches Pt-Atom pro Einheitszelle aufweist, das zus{\"a}tzlich um einen Wert von \unit{0.26}{\angstrom} aus der Oberfl{\"a}che hervorsteht. Die La-Atome, die direkt unterhalb der Terminierungslage liegen, erfahren eine Verschiebung in entgegengesetzter Richtung, so dass im Vergleich zum Volumen der Filme eine lokal ver{\"a}nderte Symmetrie im oberfl{\"a}chennahen Bereich vorherrscht und sich auf die elektronischen Eigenschaften der LaPt\$_5\$-Filme auswirkt. Dar{\"u}ber hinaus wurden die Schwingungseigenschaften der LaPt\$_5\$-Filme mittels der polarisierten in situ Raman-Spektroskopie bestimmt, bei der die auftretenden Schwingungspeaks durch die Kenntnis der atomaren Struktur und mit {\"U}berlegungen aus der Gruppentheorie unterschiedlichen Tiefenbereichen der LaPt\$_5\$-Filme (Volumen und Oberfl{\"a}che) zugewiesen werden konnten. Im zweiten experimentellen Kapitel liegt der Fokus auf der atomaren Struktur sowie auf den elektronischen und magnetischen Eigenschaften des Kondo- und Schwerfermionensystems CePt\$_5\$/Pt(111). In Abh{\"a}ngigkeit von der vor dem Legierungsprozess angebotenen Menge an Ce-Atomen auf dem Pt(111)-Substrat konnten insgesamt sieben verschiedene LEED-Phasen der CePt\$_5\$-Filme identifiziert werden, deren jeweilige Oberfl{\"a}chenrekonstruktionen durch eine unterschiedliche Rotationsausrichtung in Bezug auf das Pt(111)-Substrat gekennzeichnet sind. Zus{\"a}tzlich ist die laterale Gitterkonstante einem Prozess aus Verspannung und Dehnung aufgrund der Gitterfehlanpassung von Film und Substrat ausgesetzt. Eine durchgef{\"u}hrte LEED-IV Analyse best{\"a}tigt das Wachstum der Filme in der CaCu\$_5\$-Struktur mit einer Pt-reichen Oberfl{\"a}chenabschlusslage, deren Pt\$_3\$-Kagom\'{e}-Lage im Vergleich zum Volumengitter mit einem zus{\"a}tzlichen Pt-Atom pro Einheitszelle gef{\"u}llt ist. Die strukturellen Ergebnisse stimmen mit erzielten Resultaten aus fr{\"u}heren Arbeiten {\"u}berein und verdeutlichen zudem die isostrukturellen Eigenschaften zur intermetallischen Oberfl{\"a}chenlegierung LaPt\$_5\$/Pt(111). Dies erm{\"o}glicht durch geeignete Vergleichsexperimente an LaPt\$_5\$/Pt(111) die induzierten Ph{\"a}nomene der \$4f\$-Elektronen bez{\"u}glich des Kondo- und Schwerfermionenverhaltens bei CePt\$_5\$/Pt(111) zu bestimmen, da La-Atome in ihrem atomaren Aufbau keine \$4f\$-Elektronen beherbergen. Mit der polarisierten in situ Raman-Spektroskopie aufgenommene Spektren anhand von unterschiedlich dicken CePt\$_5\$-Filmen beinhalten sowohl charakteristische Schwingungspeaks als auch elektronische {\"U}berg{\"a}nge. Das spektroskopische Verhalten der Schwingungspeaks zeigt dabei nicht nur Gemeinsamkeiten zu LaPt\$_5\$/Pt(111) bei der Zuweisung der Schwingungsmoden zu den jeweiligen Tiefenbereichen in den CePt\$_5\$-Filmen, sondern es treten auch Unterschiede auf, da eine CePt\$_5\$-Schwingungsmode einem anormalen Temperaturverhalten unterliegt, das auf die Wechselwirkung mit den \$4f\$-Elektronen zur{\"u}ckzuf{\"u}hren ist. Weitere spezifische Raman-Signaturen, die elektronischen {\"U}berg{\"a}ngen in Form von Kristallfeldniveauaufspaltungen der \$4f\$-Elektronen von Ce zugewiesen werden konnten, resultieren ebenfalls aus unterschiedlichen Regionen der CePt\$_5\$-Filme (Oberfl{\"a}che, inneres Volumen, Interface). Die magnetischen Eigenschaften der CePt\$_5\$-Filme wurden mit XAS und XMCD an den Ce M\$_{4,5}\$-Kanten in Abh{\"a}ngigkeit von der Temperatur, dem Einfallswinkel, der Filmdicke und der St{\"a}rke des Magnetfelds analysiert. Die markanten {\"U}berg{\"a}nge zwischen unterschiedlichen Curie-Weiss-Regimen in der inversen Suszeptibilit{\"a}t erlauben R{\"u}ckschl{\"u}sse {\"u}ber das Kristallfeldaufspaltungsschema, die Kondo- und die RKKY-Wechselwirkung und korrelieren mit der Ce-Valenz. Zudem konnte bei tiefen Temperaturen ein {\"U}bergang in den koh{\"a}renten Schwerfermionen-Zustand f{\"u}r alle untersuchten CePt\$_5\$-Filmdicken in dieser Arbeit nachgewiesen werden. Durch die Vorhersage eines metamagnetischen Lifshitz-{\"U}bergangs f{\"u}r diese Filme, der sich in der Magnetfeldabh{\"a}ngigkeit des magnetischen Moments {\"a}ußert, konnte durch die Aufnahme von Magnetisierungskurven bei tiefen Temperaturen und hohen Magnetfeldern auf zwei weitere charakteristische Energieskalen der renormalisierten Bandstruktur zugegriffen werden. Das dritte experimentelle Kapitel widmet sich der mit LEED und LEED-IV durchgef{\"u}hrten Aufkl{\"a}rung der atomaren Struktur eines quasi-eindimensionalen Elektronensystems, bei dem sich die gebildeten Au-Nanodr{\"a}hte auf der Si(111)-Oberfl{\"a}che durch eine Si(111)-(5\$\times\$2)-Au Rekonstruktion beschreiben lassen. Die aufgenommenen LEED-Bilder mit ihren markanten Beugungsreflexen und sogenannten Streifen deuten auf drei gleichwertige Rotationsdom{\"a}nen, die jeweils um einen Winkel von \unit{120}{\degree} gegeneinander gedreht sind, auf der Oberfl{\"a}che hin. Zudem konnte aus einer Simulation der Beugungsbilder das Auftreten von Streifen durch drei zus{\"a}tzliche Spiegeldom{\"a}nen, die eine Phasenverschiebung von einem halben {\"U}berstrukturvektor einf{\"u}hren und bei einer sorgf{\"a}ltigen LEED-IV Analyse ebenfalls ber{\"u}cksichtigt werden sollten, erkl{\"a}rt werden. Aus den in der Literatur nach einer zweiten Rekalibrierung der n{\"o}tigen Menge an Au-Atomen zur Ausbildung der Si(111)-(5\$\times\$2)-Au Rekonstruktion in den letzten Jahren heftig diskutierten Strukturmodellen gibt das von Kwon und Kang aufgestellte Geometriemodell (KK-Modell) die beobachteten energieabh{\"a}ngigen Intensit{\"a}tsmodulationen in den experimentellen Daten beim Vergleich mit theoretisch berechneten IV-Kurven am besten wieder. F{\"u}r dieses Modell nimmt der R-Faktor nach Pendry bei den unabh{\"a}ngig voneinander betrachteten drei Energieserien unter verschiedenen Einfallswinkeln der Elektronen auf die Probenoberfl{\"a}che stets den kleinsten Wert an. Unter der expliziten Ber{\"u}cksichtigung von Si-Adatomen, die sich zus{\"a}tzlich auf der Oberfl{\"a}che befinden und in einer (5\$\times\$4)-Einheitszelle beschrieben werden k{\"o}nnen, bleibt das KK-Modell das zu pr{\"a}ferierende Strukturmodell zur Beschreibung der ausgebildeten Au-Ketten und der Si-Honigwabenstruktur bei der Si(111)-(5\$\times\$2)-Au Oberfl{\"a}chenrekonstruktion. Im letzten experimentellen Kapitel wird ein zweidimensionales Elektronensystem -- die \$\alpha\$-Si(111)-(\$\sqrt{3}\times\sqrt{3}\$)R30\${\degree}\$-Sn Oberfl{\"a}chenrekonstruktion, die sich bei 1/3 ML an Sn-Adsorbaten auf dem Si(111)-Substrat ausbildet -- im Hinblick auf die atomare Struktur bei Raumtemperatur mit LEED und LEED-IV untersucht. Aus den insgesamt sechs in die Analyse aufgenommenen Strukturmodellen, bei denen die Sn-Atome innerhalb der rekonstruierten (\$\sqrt{3}\times\sqrt{3}\$)R30\${\degree}\$-Einheitszelle unterschiedliche Adsorptionspl{\"a}tze auf einer ideal terminierten Si(111)-Oberfl{\"a}che einnehmen, konnte ein Legierungsverhalten, wie es bei der \$\gamma\$-Si(111)-(\$\sqrt{3}\times\sqrt{3}\$)R30\${\degree}\$-Sn Phase auftritt, ausgeschlossen werden. Die Sn-Atome ordnen sich ausschließlich auf der Oberfl{\"a}che neu an und f{\"u}hren zu einer Relaxation des darunterliegenden Substrats, deren atomare Verschiebungen sich bis in die sechste Si-Lage nachverfolgen lassen. Im Vergleich zu fr{\"u}heren Strukturaufkl{\"a}rungen an diesem Materialsystem best{\"a}tigt diese Analyse, dass sich die abgeschiedenen Sn-Atome auf T\$_4\$-Adsorptionspl{\"a}tzen energetisch g{\"u}nstig anlagern, wobei die bei drei unterschiedlichen Einfallswinkeln aufgenommenen experimentellen Daten an unterschiedlichen Probenpositionen auf ein vorhandenes bzw. fehlendes Si-Atom auf einem S\$_5\$-Gitterplatz im darunterliegenden Si(111)-Substrat hindeuten. Außerdem konnte das theoretisch vorhergesagte dynamische Fluktuations-Modell aufgrund der sehr stark erh{\"o}hten thermischen Auslenkungen der Sn-Atome aus ihrer Gleichgewichtslage in den Modellrechnungen zur dynamischen Streutheorie nachgewiesen werden. Dies k{\"o}nnte neben den unregelm{\"a}ßig angeordneten Si-Fehlstellen eine Ursache f{\"u}r das Ausbleiben des strukturell reversiblen Phasen{\"u}bergangs von einer (\$\sqrt{3}\times\sqrt{3}\$)R30\${\degree}\$-Phase zu einer (3\$\times\$3)-Phase bei tiefen Temperaturen, wie er beispielsweise beim elektronisch vergleichbaren Adsorbatsystem Ge(111)-(\$\sqrt{3}\times\sqrt{3}\$)R30\${\degree}\$-Sn auftritt, sein.},
  subject      = {Schwere-Fermionen-System},
  language  = {de}
}
@phdthesis{Zimmermann2020,
  author    = {Zimmermann, Henriette},
  title     = {Antigenic variation and stumpy development in \(Trypanosoma\) \(brucei\)},
  doi       = {10.25972/OPUS-14690},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146902},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {The eukaryotic parasite Trypanosoma brucei has evolved sophisticated strategies to persist within its mammalian host. Trypanosomes evade the hosts' immune system by antigenic variation of their surface coat, consisting of variant surface glycoproteins (VSGs). Out of a repertoire of thousands of VSG genes, only one is expressed at any given time from one of the 15 telomeric expression sites (ES). The VSG is stochastically exchanged either by a transcriptional switch of the active ES (in situ switch) or by a recombinational exchange of the VSG within the active ES. However, for infections to persist, the parasite burden has to be limited. The slender (sl) bloodstream form secretes the stumpy induction factor (SIF), which accumulates with rising parasitemia. SIF induces the irreversible developmental transition from the proliferative sl to the cell cycle-arrested but fly-infective stumpy (st) stage once a concentration threshold is reached. Thus, antigenic variation and st development ensure persistent infections and transmissibility. A previous study in monomorphic cells indicated that the attenuation of the active ES could be relevant for the development of trypanosomes. The present thesis investigated this hypothesis using the inducible overexpression of an ectopic VSG in pleomorphic trypanosomes, which possess full developmental competence. These studies revealed a surprising phenotypic plasticity: while the endogenous VSG was always down-regulated upon induction, the ESactivity determined whether the VSG overexpressors arrested in growth or kept proliferating. Full ES-attenuation induced the differentiation of bona fide st parasites independent of the cell density and thus represents the sole natural SIF-independent differentiation trigger to date. A milder decrease of the ES-activity did not induce phenotypic changes, but appeared to prime the parasites for SIF-induced differentiation. These results demonstrate that antigenic variation and development are linked and indicated that the ES and the VSG are independently regulated. Therefore, I investigated in the second part of my thesis how ES-attenuation and VSG-silencing can be mediated. Integration of reporters with a functional or defective VSG 3'UTR into different genomic loci showed that the maintenance of the active state of the ES depends on a conserved motif within the VSG 3'UTR. In situ switching was only triggered when the telomere-proximal motif was partially deleted, suggesting that it serves as a DNA-binding motif for a telomere-associated protein. The VSG levels seem to be additionally regulated in trans based on the VSG 3'UTR independent of the genomic context, which was reinforced by the regulation of a constitutively expressed reporter with VSG 3' UTR upon ectopic VSG overexpression.},
  subject      = {Trypanosoma brucei},
  language  = {en}
}
@phdthesis{Zimmermann2020,
  author    = {Zimmermann, Benjamin Georg Heinz},
  title     = {Zytokinstimulation von mononukle{\"a}ren Zellen des peripheren Blutes (PBMC) von Patienten mit Diabetes Mellitus Typ 1},
  doi       = {10.25972/OPUS-19962},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199622},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Diabetes mellitus Typ 1 ist eine chronische Autoimmunerkrankung, die {\"u}ber eine Zerst{\"o}rung pankreatischer Beta-Zellen der Langerhans-Inseln zu einem absoluten Insulinmangel f{\"u}hrt. Urs{\"a}chlich f{\"u}r die Zerst{\"o}rung des Pankreasgewebes sind autoreaktive T-Zellen, die eine Entz{\"u}ndungsreaktion (Insulitis) im Pankreas bewirken. Zentrales Thema der Promotionsarbeit ist die Erforschung grundlegender quantitativer und qualitativer Eigenschaften von T-Zellen von Diabetikern im Vergleich zu gesunden, alters-gleichen Kontrollpersonen. Der Fokus der Arbeit liegt dabei auf der Analyse von naiven T-Zellen und ihrer Polarisierbarkeit in proinflammatorische Th17 (Interleukin-17-produzierende) Zellen und regulatorische T-Zellen (Tregs), die die Inflammation unterdr{\"u}cken k{\"o}nnen. Voruntersuchungen der Arbeitsgruppe zeigten tendenziell eine proportionale Vermehrung von proinflammatorischen T-Zellen (Th17 Zellen) im peripheren Blut von Typ1 Diabetikern. Aus dem Vollblut wurden mittels Ficoll-Dichtezentrifugation periphere mononukle{\"a}re Zellen des Blutes (PBMC) gewonnen. {\"U}ber magnetisch aktivierte Zell-Separation (MACS) wurden naive T-Zellen (CD4+CD45RA+CD27+) aus den PBMCs isoliert. Diese naiven Zellen wurden angeregt sich zu adulten, immunkompetenten Zellen zu differenzieren. Die Antigenstimulation der T-Zellen wurde imitiert durch Aktivierung mit Antik{\"o}rpern gegen die Molek{\"u}le CD3 und CD28 oder einem C. albicans-Antigen. Die Stimulation wurde unter Co-Kultivierung mit autologen antigenpr{\"a}sentierenden Zellen durchgef{\"u}hrt. Die Richtung der Differenzierung wurde durch Zugabe verschiedener Zytokin-Cocktails beeinflusst. Nach Abschluss der Kultivierung wurde sowohl der Ph{\"a}notyp der Zellen als auch deren F{\"a}higkeit bestimmte Zytokine zu produzieren mittels Durchflusszytometrie (FACS) bestimmt. Weiterhin wurden Suppressionsassays durchgef{\"u}hrt, bei denen die Suppressionsf{\"a}higkeit von aus naiven T-Zellen induzierten Tregs auf autologe PBMCs von Typ 1 Diabetes Patienten {\"u}berpr{\"u}ft wurde. In dem zun{\"a}chst durchgef{\"u}hrten Vergleich von Kindern mit einer Erstmanifestation mit gesunden Kontrollen konnte eine st{\"a}rkere IFN-Produktion gezeigt werden mit signifikanten Unterschieden innerhalb der Ki67+ Zellen. Interessanterweise zeigte sich diese st{\"a}rkere IFN Sekretion der T-Zellen der Diabetiker unter Bedingungen, die die Expression von TH17-Zellen f{\"o}rdern sollten. Zus{\"a}tzlich konnten T-Zellen nachgewiesen werden, die f{\"u}r IFN und IL17 doppelt positiv waren. In weiteren Versuchen wurden auch Vergleiche zwischen l{\"a}ngere Zeit an Diabetes erkrankten Kindern und erwachsenen Diabetikern mit gesunden Kontrollen durchgef{\"u}hrt. Bei den erwachsenen Diabetikern konnten dabei mehr IFN+/IL17+ T Zellen innerhalb der Ki67+ T-Zellen nachgewiesen werden als bei den Kontrollen. Die Zellkulturexperimente wurden im Weiteren mit C. albicans-Antigen als einem spezifischen Stimulus des Immunsystems durchgef{\"u}hrt. Die Untersuchung zeigte zun{\"a}chst einmal, dass das C. albicans-Antigen bez{\"u}glich Proliferation und T-Zell-Differenzierung ein deutlich schw{\"a}cherer Stimulus im Vergleich zur Stimulation mit aCD3/aCD28 war. Beobachtet werden konnte allerdings, dass es durch Stimulation mit dem C. albicans-Antigen insgesamt zu einer st{\"a}rkeren Aktivierung des TH17-Zell-Systems kam mit Ausnahme der l{\"a}ngere Zeit an einem Diabetes erkrankten Kinder, die eine geringere IL17-Produktion im Vergleich zu den Kontrollen aufwiesen. Insgesamt zeigten sich teils deutliche Unterschiede zwischen den Gruppen der Diabetiker, so dass von einer Beeinflussung der Ergebnisse durch Krankheitsdauer, Krankheitsaktivit{\"a}t, Alter der Probanden und Therapiedauer ausgegangen werden muss. Die Untersuchung des Proliferationsverhaltens ergab sowohl bei den proinflammatorischen T-Zellen als auch bei den Tregs keine Unterschiede zwischen den Diabetikern und den Kontrollpatienten, ebenso wie die quantitative Untersuchung der Ausbildung von CD25+FOXP3+ Tregs aus den naiven T-Zellen unter unspezifischer Stimulation. Unter spezifischer Stimulation hingegen zeigten sich mehr Tregs bei den Kindern mit einer Erstmanifestation und den erwachsenen Diabetikern. Ebenfalls unter Stimulation mit dem C. albicans-Antigen zeigten sich unter proinflammatorischen Bedingungen bei den Kindern mit einer Erstmanifestation und unter antiinflammatorischen Bedingungen bei den erwachsenen Diabetikern ein signifikant h{\"o}herer Anteil CD127- Tregs (CD25+FOXP3+) im Vergleich zu den Kontrollprobanden. Interessanterweise zeigte sich bei den erwachsenen Diabetikern sowohl bei spezifischer als auch bei unspezifischer Stimulation eine st{\"a}rkere Produktion von IL17 durch die Tregs. Die Untersuchung der Expression des Homing-Rezeptors CD62L auf den Tregs ergab keine signifikanten Unterschiede, aber eine h{\"o}here Expression bei allen Diabetikern im Vergleich zu den jeweiligen Kontrollgruppen und die Untersuchung des IFN-Rezeptors erbrachte keine signifikanten Unterschiede zwischen den Gruppen, allerdings zeigten sich die Mediane und Mittelwerte bei den Kindern mit einer Erstmanifestation im Vergleich zu den Kontrollen bei unspezifischer Stimulation erh{\"o}ht. Zur Erg{\"a}nzung der Zellkulturexperimente wurden im Weiteren Suppressionsversuche mit aus naiven T-Zellen induzierten Tregs durchgef{\"u}hrt. Die Suppressionsversuche konnten eine geringere Hemmung der Proliferation durch die induzierten Tregs der Diabetiker zeigen und damit auf eine m{\"o}gliche Dysfunktion der Tregs deuten. Um M{\"o}glichkeiten der Beeinflussung des Immunsystems zu untersuchen wurden die Zellkulturen erneut unter Blockade von IFNy und Zugabe von TGFb durchgef{\"u}hrt. Die Blockade von IFNy f{\"u}hrte zu einer geringer ausgepr{\"a}gten Differenzierung und Proliferation der T-Zellen. Weiterhin konnten in der intrazellul{\"a}ren F{\"a}rbung weniger IFN positive T-Zellen gefunden werden und es zeigte sich eine st{\"a}rkere Expression des IFN-Rezeptors. Bei den Kindern mit einer Erstmanifestation zeigte sich zus{\"a}tzlich auch eine geringere Auspr{\"a}gung der IL17+ T-Zellen. Hier ergaben sich keine Unterschiede in der Quantit{\"a}t der Tregs. Die erwachsenen Diabetiker zeigten hier weniger Tregs, daf{\"u}r aber eine st{\"a}rkere Proliferation innerhalb der Tregs. Bei den Kindern mit einem l{\"a}ngere Zeit bestehenden Diabetes hingegen zeigten sich keine quantitativen Unterschiede. Die Beeinflussung durch Zugabe von TGFb bei den erwachsenen Diabetikern und den Kindern mit einer Erstmanifestation f{\"u}hrte zu einer geringeren T-Zell Differenzierung mit mehr naiven T-Zellen und weniger Memory-T-Zellen sowie zu einer geringeren IFNy Expression. Bei den Erwachsenen zeigte sich ebenso eine geringere Proliferation, geringe Anzahlen f{\"u}r Tregs sowie eine geringe Auspr{\"a}gung der Expression von CD62L und der Produktion von IL17 durch Tregs. Insgesamt konnte gezeigt werden, dass es Unterschiede zwischen den proinflammatorischen T-Zellen sowie den induzierten Tregs der Diabetiker im Vergleich zu den gesunden Kontrollen gibt. Insbesondere die Bedeutung von IFNy bei den Erstmanifestation konnte gezeigt werden. Aber auch die Sekretion von IL17 oder die Expression von CD62L auf den Tregs stellen interessante Ansatzpunkte zur weiteren Erforschung des Diabetes dar. Weiterhin zeigten die Suppressionsversuche eine gest{\"o}rte Regulation durch die induzierten Tregs bei den Diabetikern. Sowohl die Blockade von IFNy als auch die Zugabe von TGFb zeigten inflammationshemmende Wirkung bei den Lymphozyten der Diabetiker in vitro und stellen interessante Ansatzpunkt f{\"u}r eine m{\"o}gliche Therapie dar.},
  subject      = {Regulatorischer T-Lymphozyt},
  language  = {de}
}
@article{Ziegler2020,
  author    = {Ziegler, Robert Hugo},
  title     = {Die R{\"u}ckkehr des Realen},
  series = {Deutsche Zeitschrift f{\"u}r Philosophie},
  volume    = {68},
  journal   = {Deutsche Zeitschrift f{\"u}r Philosophie},
  number    = {4},
  issn      = {2192-1482},
  doi       = {10.1515/dzph-2020-0040},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217771},
  pages     = {611 -- 626},
  year      = {2020},
  abstract  = {We are witnessing a return of the real which philosophy seems illequipped to handle. I argue (1) that this return of the real must be read as a rejection of those philosophical tendencies which were prevalent in the past decades and which I call philosophies of mediation: They supplanted all references to something real by the sole reference to those processes in which reality was supposed to be given or shaped (in interpretations, linguistic structures, historical or social conditions, media…). The current urgency of the question of the real indicates that those philosophies have lost credibility. On the other hand (2), the contemporary attempts to resuscitate philosophical realism cannot be considered satisfactory either. It is curiously the real itself they fail to fully appreciate. All in all (3), the return of the real has to be interpreted as the effect of an event that has little to do with philosophy, namely the return of politics.},
  language  = {de}
}
@article{ZieglerPollingerBoelletal.2020,
  author    = {Ziegler, Katrin and Pollinger, Felix and B{\"o}ll, Susanne and Paeth, Heiko},
  title     = {Statistical modeling of phenology in Bavaria based on past and future meteorological information},
  series = {Theoretical and Applied Climatology},
  volume    = {140},
  journal   = {Theoretical and Applied Climatology},
  issn      = {0177-798X},
  doi       = {10.1007/s00704-020-03178-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232717},
  pages     = {1467-1481},
  year      = {2020},
  abstract  = {Plant phenology is well known to be affected by meteorology. Observed changes in the occurrence of phenological phases arecommonly considered some of the most obvious effects of climate change. However, current climate models lack a representationof vegetation suitable for studying future changes in phenology itself. This study presents a statistical-dynamical modelingapproach for Bavaria in southern Germany, using over 13,000 paired samples of phenological and meteorological data foranalyses and climate change scenarios provided by a state-of-the-art regional climate model (RCM). Anomalies of severalmeteorological variables were used as predictors and phenological anomalies of the flowering date of the test plantForsythiasuspensaas predictand. Several cross-validated prediction models using various numbers and differently constructed predictorswere developed, compared, and evaluated via bootstrapping. As our approach needs a small set of meteorological observationsper phenological station, it allows for reliable parameter estimation and an easy transfer to other regions. The most robust andsuccessful model comprises predictors based on mean temperature, precipitation, wind velocity, and snow depth. Its averagecoefficient of determination and root mean square error (RMSE) per station are 60\% and ± 8.6 days, respectively. However, theprediction error strongly differs among stations. When transferred to other indicator plants, this method achieves a comparablelevel of predictive accuracy. Its application to two climate change scenarios reveals distinct changes for various plants andregions. The flowering date is simulated to occur between 5 and 25 days earlier at the end of the twenty-first century comparedto the phenology of the reference period (1961-1990).},
  language  = {en}
}
@article{ZieglerAlmosMcNeilletal.2020,
  author    = {Ziegler, Georg C. and Almos, Peter and McNeill, Rhiannon V. and Jansch, Charline and Lesch, Klaus-Peter},
  title     = {Cellular effects and clinical implications of SLC2A3 copy number variation},
  series = {Journal of Cellular Physiology},
  volume    = {235},
  journal   = {Journal of Cellular Physiology},
  number    = {12},
  doi       = {10.1002/jcp.29753},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218009},
  pages     = {9021 -- 9036},
  year      = {2020},
  abstract  = {SLC2A3 encodes the predominantly neuronal glucose transporter 3 (GLUT3), which facilitates diffusion of glucose across plasma membranes. The human brain depends on a steady glucose supply for ATP generation, which consequently fuels critical biochemical processes, such as axonal transport and neurotransmitter release. Besides its role in the central nervous system, GLUT3 is also expressed in nonneural organs, such as the heart and white blood cells, where it is equally involved in energy metabolism. In cancer cells, GLUT3 overexpression contributes to the Warburg effect by answering the cell's increased glycolytic demands. The SLC2A3 gene locus at chromosome 12p13.31 is unstable and prone to non-allelic homologous recombination events, generating multiple copy number variants (CNVs) of SLC2A3 which account for alterations in SLC2A3 expression. Recent associations of SLC2A3 CNVs with different clinical phenotypes warrant investigation of the potential influence of these structural variants on pathomechanisms of neuropsychiatric, cardiovascular, and immune diseases. In this review, we accumulate and discuss the evidence how SLC2A3 gene dosage may exert diverse protective or detrimental effects depending on the pathological condition. Cellular states which lead to increased energetic demand, such as organ development, proliferation, and cellular degeneration, appear particularly susceptible to alterations in SLC2A3 copy number. We conclude that better understanding of the impact of SLC2A3 variation on disease etiology may potentially provide novel therapeutic approaches specifically targeting this GLUT.},
  language  = {en}
}
@phdthesis{Ziegler2020,
  author    = {Ziegler, Anja},
  title     = {In-vitro Evaluation des Einflusses der Lokalan{\"a}sthetika Ropivacain und Bupivacain auf die Kontraktilit{\"a}t des humanen Herzmuskels},
  doi       = {10.25972/OPUS-21046},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-210465},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Der Einsatz von Regionalan{\"a}sthesien nahm in den letzten Jahren stark zu. Durch die Blockade von spannungsabh{\"a}ngigen Natriumkan{\"a}len verhindern Lokalan{\"a}sthetika eine Depolarisation sowie die neuronale Fortleitung der Schmerzimpulse. In h{\"o}heren Dosierungen kann es jedoch zu ausgedehnten Blockaden im Myokard mit toxischen Wirkungen auf die Funktion der Muskelzellen kommen. Bis zur Einf{\"u}hrung der Lipidemulsionen als Behandlungsoption bei einer Lokalan{\"a}sthetikaintoxikation war eine prolongierte kardio-pulmonale Reanimation die einzige therapeutische Option. In dieser Arbeit wurden die aktuell h{\"a}ufig verwendeten langwirksamen Substanzen Bupivacain und Ropivacain hinsichtlich einer divergierenden Kardiotoxizit{\"a}t verglichen und die Pr{\"a}inkubation mit Lipofundin® als M{\"o}glichkeit zur Reduktion der Kardiotoxizit{\"a}t getestet. Mit Zustimmung der Ethikkommission wurden insgesamt 46 humane Herzmuskelb{\"u}ndel in einem Organbad untersucht. Es erfolgte im Abstand von drei Minuten eine Inkubation mit Koffein in steigenden Konzentrationen (0,5; 1,0; 1,5; 2,0; 3,0; 4,0 mmol/l) und nachfolgend die Applikation von handels{\"u}blichen L{\"o}sungen von Lokalan{\"a}sthetika (50 - 100 - 150 µl). Es wurden entweder Bupivacain (0,25, 0,5, 0,75 mg), Ropivacain (0,375, 0,75, 1,125 mg) oder Ropivacain in Kombination mit Lipofundin® 20\% N (200µl in Verd{\"u}nnung 1:100) appliziert. Abschließend erfolgte die hochdosierte Gabe von Koffein (Gesamtkonzentration 32 mmol/l), um eine maximale Kontraktur auszul{\"o}sen. Es zeigte sich kein signifikanter Unterschied zwischen Bupivacain und Ropivacain hinsichtlich der Kontraktionsamplitude und der Grundspannung bei {\"a}hnlichem Verhalten in beiden Gruppen. Die Pr{\"a}inkubation mit Lipofundin® ergab im Vergleich zur Kontrollgruppe keinen signifikanten Effekt. Eine signifikante konzentrationsabh{\"a}ngige Abnahme der Kontraktionsamplitude und der Grundspannung zeigte sich w{\"a}hrend der initialen Inkubation mit Koffein. Initiale Sch{\"a}digungen, passagere Erm{\"u}dungserscheinungen oder hypoxische Stoffwechselzust{\"a}nde k{\"o}nnten trotz bestm{\"o}glicher Bedingungen die Ergebnisse beeintr{\"a}chtigt haben. Die vorliegenden in-vitro-Ergebnisse lassen sich nur limitiert auf in-vivo-Bedingungen {\"u}bertragen und verlangen nach weiteren Studien, die eine differenzierte und pr{\"a}zise Wirkweise sowie Dosierung von Lipidemulsionen evaluieren.},
  subject      = {Lokalan{\"a}sthesie},
  language  = {de}
}
@phdthesis{Zhu2020,
  author    = {Zhu, Mo},
  title     = {Germination and differentiation of \(Blumeria\) \(graminis\) ascospores and effects of UV-C and white light irradiation on \(B.\) \(graminis\) conidial prepenetration},
  doi       = {10.25972/OPUS-16647},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166470},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Blumeria graminis, the obligate biotrophic grass powdery mildew, is a highly pathogenic fungus capable of inflicting foliar diseases and of causing severe yield losses. There is asexual and sexual propagation in the life cycle of B. graminis. In the epidemiological processes of this pathogen, both types of spores - asexual conidia and sexual ascospores - are crucial. Conidia of B. graminis are demonstrated to perceive cuticular very-long-chain aldehydes as molecular signal substances notably promoting germination and differentiation of the infection structure (the appressorium) - the prepenetration processes - in a concentration- and chain-length-dependent manner. Conidial germination and appressorium formation are known to be dramatically impeded by the presence of free water on the host surface. However, sexually formed ascospores are reported to easily germinate immersed in water. There are abundant assays on conidial prepenetration processes. However, with respect to the stimulating effects of very-long-chain aldehydes and to the influence of the presence of free water, ascosporic prepenetration processes are still obscure. In order to study the effects of very-long-chain aldehydes on the ascosporic prepenetration processes of wheat powdery mildew fungus B. graminis f. sp. tritici, Formvar®-based in vitro systems were applied to exclude the secondary host effects (such as host resistance) and to reproducibly provide homogeneous hydrophobic substratum surfaces. By the presence of even-numbered very-long-chain aldehydes (C22 - C30), the appressorium formation of the ascospores was notably triggered in a chain-length dependent manner. N-octacosanal (C28) was the most inducing aldehyde tested. Unlike conidia, ascospores could easily differentiate immersed in water and showed a more variable differentiation pattern even with a single germ tube differentiating an appressorium. To evaluate the alternative management against barley powdery mildew fungus Blumeria graminis f. sp. hordei, the suppressing effects of UV-C irradiation on the developmental processes of conidia on artificial surfaces (in vitro) and on host leaf surfaces (in vivo) were assayed. In vitro and in vivo, a single dose of 100 J m-2 UV-C was adequate to decrease conidial germination to < 20 \% and to reduce appressorium formation to values < 5 \%. UV-C irradiation negatively affected colony pustule size and vegetative propagation. Under photoperiodic conditions of 2h light/16h dark, 6h dark/12h light or 6h dark/18h light, UV-C-treated conidia showed photoreactivation (photo-recovery). White light-mediated photoreactivation was most effective immediately after UV-C irradiation, suggesting that a prolonged phase of darkness after UV-C application increased the efficacy of management against B. graminis. UV-C irradiation increased transcript levels of three putative photolyase genes in B. graminis, indicating those were probably involved in photoreactivation processes. However, mere white light or blue light (wavelength peak, 475 nm) could not induce the up-regulation of these genes. To determine whether visible light directly impacted the prepenetration and penetration processes of this powdery mildew pathogen, conidia of Blumeria graminis f. sp. hordei and Blumeria graminis f. sp. tritici were inoculated onto artificial surfaces and on host leaf surfaces. Samples were analyzed after incubation periods under light conditions (white light intensity and spectral quality). Increasing white light intensities directly impaired conidial prepenetration processes in vitro but not in vivo. Applying an agar layer under the wax membrane compensated for conidial water loss as a consequence of high white light irradiation. Light stimulated in vitro and in vivo the appressorium elongation of B. graminis in a wavelength-dependent manner. Red light was more effective to trigger the elongation of appressorium than blue light or green light assayed. Taken together, the findings of this study demonstrate that 1) a host surface recognition principle based on cuticular very-long-chain aldehydes is a common feature of B. graminis f. sp. tritici ascospores and conidia; 2) the transcriptional changes of three putative photolyase genes in B. graminis are mediated in a UV-C-dependent manner; 3) light directly affected the (pre)penetration processes of B. graminis.},
  subject      = {Blumeria graminis},
  language  = {en}
}
@article{ZhouSteinhardtDuelletal.2020,
  author    = {Zhou, Xiang and Steinhardt, Maximilian Johannes and D{\"u}ll, Johannes and Krummenast, Franziska and Danhof, Sophia and Meckel, Katharina and Nickel, Katharina and Grathwohl, Denise and Leicht, Hans-Benno and Rosenwald, Andreas and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, Martin},
  title     = {Obinutuzumab and venetoclax induced complete remission in a patient with ibrutinib-resistant non-nodal leukemic mantle cell lymphoma},
  series = {European Journal of Haematology},
  volume    = {104},
  journal   = {European Journal of Haematology},
  number    = {4},
  doi       = {10.1111/ejh.13382},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215513},
  pages     = {352 -- 355},
  year      = {2020},
  abstract  = {We herein report the case of a 73-year-old male patient who was diagnosed with leukemic non-nodal MCL. This patient had received six cycles of bendamustine, which resulted in a transient remission, and a second-line therapy with ibrutinib, which unfortunately failed to induce remission. We started a treatment with single-agent obinutuzumab at a dose of 20 mg on day 1, 50 mg on day 2-4, 330 mg on day 5, and 1000 mg on day 6. The laboratory analysis showed a rapid decrease of leukocyte count. Four weeks later, we repeated the treatment with obinutuzumab at a dose of 1000 mg q4w and started a therapy with venetoclax at a dose of 400 mg qd, which could be increased to 800 mg qd from the third cycle. This combination therapy was well tolerated. The patient achieved a complete remission (CR) after three cycles of obinutuzumab and venetoclax. To date, the patient has a progression-free survival of 17 months under ongoing obinutuzumab maintenance q4w. This is the first report about obinutuzumab and venetoclax induced CR in rituximab-intolerant patient with an ibrutinib-resistant MCL. This case suggests that obinutuzumab- and venetoclax-based combination therapy might be salvage therapy in patients with ibrutinib-resistant MCL.},
  language  = {en}
}
@article{ZhouSteinhardtGrathwohletal.2020,
  author    = {Zhou, Xiang and Steinhardt, Maximilian J. and Grathwohl, Denise and Meckel, Katharina and Nickel, Katharina and Leicht, Hans-Benno and Krummenast, Franziska and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, Klaus M.},
  title     = {Multiagent therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab ("Pom-PAD-Dara") in relapsed/refractory multiple myeloma},
  series = {Cancer Medicine},
  volume    = {9},
  journal   = {Cancer Medicine},
  number    = {16},
  doi       = {10.1002/cam4.3209},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218029},
  pages     = {5819-5826},
  year      = {2020},
  abstract  = {Background Even in the era of novel immunotherapies for multiple myeloma (MM), treatment of late-stage relapsed/refractory (RR) patients remains challenging. The aim of our study was to analyze the efficacy and safety of the five-drug combination pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab ("Pom-PAD-Dara") in RRMM. Methods We retrospectively analyzed data of 56 patients with RRMM who received Pom-PAD-Dara between September 2016 and May 2019. Results Patients were heavily pretreated with a median of four prior lines of therapy, including autologous and allogenic stem cell transplant in 50 (89\%) and six (11\%) patients, respectively. The overall response rate (ORR) was 78\% and we observed partial remission, very good partial remission, and complete remission in 27 (48\%), 13 (23\%) and four (7\%) patients, respectively. Median progression-free survival was 7 months (95\% CI, 3.3-10.7) and the median overall survival was not reached at 24 months. Adverse events grade ≥ 3 were observed 41 (73\%) patients and included neutropenia (n = 28, 50\%), anemia (n = 22, 39\%), thrombocytopenia (n = 21, 38\%), and pneumonia (n = 6, 11\%). Conclusion Pom-PAD-Dara represents a promising multiagent regimen in heavily pretreated RRMM patients with high ORR and an acceptable safety profile.},
  language  = {en}
}
@article{ZhouRascheKortuemetal.2020,
  author    = {Zhou, Xiang and Rasche, Leo and Kort{\"u}m, K. Martin and Danhof, Sophia and Hudecek, Michael and Einsele, Hermann},
  title     = {Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies},
  series = {Frontiers in Immunology},
  volume    = {11},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2020.620312},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219911},
  year      = {2020},
  abstract  = {In the last few years, monoclonal antibodies (mAbs) such as elotuzumab and daratutumab have brought the treatment of multiple myeloma (MM) into the new era of immunotherapy. More recently, chimeric antigen receptor (CAR) modified T cell, a novel cellular immunotherapy, has been developed for treatment of relapsed/refractory (RR) MM, and early phase clinical trials have shown promising efficacy of CAR T cell therapy. Many patients with end stage RRMM regard CAR T cell therapy as their "last chance" and a "hope of cure". However, severe adverse events (AEs) and even toxic death related to CAR T cell therapy have been observed. The management of AEs related to CAR T cell therapy represents a new challenge, as the pathophysiology is not fully understood and there is still no well-established standard of management. With regard to CAR T cell associated toxicities in MM, in this review, we will provide an overview of experience from clinical trials, pathophysiology, and management strategies.},
  language  = {en}
}
@article{ZhouFluechterNickeletal.2020,
  author    = {Zhou, Xiang and Fl{\"u}chter, Patricia and Nickel, Katharina and Meckel, Katharina and Messerschmidt, Janin and B{\"o}ckle, David and Knorz, Sebastian and Steinhardt, Maximilian Johannes and Krummenast, Franziska and Danhof, Sophia and Einsele, Hermann and Kort{\"u}m, K. Martin and Rasche, Leo},
  title     = {Carfilzomib based treatment strategies in the management of relapsed/refractory multiple myeloma with extramedullary disease},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {4},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12041035},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203704},
  year      = {2020},
  abstract  = {Published experience with carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) is still limited. The current study aimed to assess the efficacy and safety of carfilzomib containing therapy regimens in EMD. We retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib from June 2013 to September 2019. The median age at the start of carfilzomib was 64 (range 40-80) years. Twenty (44\%) and 25 (56\%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively. The serological overall response rate (ORR) was 59\%. Extramedullary response was evaluable in 33 patients, nine (27\%) of them achieved partial remission (PR) (ORR = 27\%). In 15 (33\%) patients, we observed no extramedullary response despite serological response. The median progression-free survival (PFS) and overall survival (OS) were five (95\% CI, 3.5-6.5) and ten (95\% CI, 7.5-12.5) months, respectively. EMD without adjacency to bone was associated with a significantly inferior PFS (p = 0.004) and OS (p = 0.04) compared to paraosseous lesions. Carfilzomib based treatment strategies showed some efficacy in heavily pretreated patients with extramedullary RRMM but could not overcome the negative prognostic value of EMD. Due to the discrepancy between serological and extramedullary response, evaluation of extramedullary response using imaging is mandatory in these patients.},
  language  = {en}
}
@article{ZhouDierksKertelsetal.2020,
  author    = {Zhou, Xiang and Dierks, Alexander and Kertels, Olivia and Samnick, Samuel and Kircher, Malte and Buck, Andreas K. and Haertle, Larissa and Knorz, Sebastian and B{\"o}ckle, David and Scheller, Lukas and Messerschmidt, Janin and Barakat, Mohammad and Truger, Marietta and Haferlach, Claudia and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, K. Martin and Lapa, Constantin},
  title     = {The link between cytogenetics/genomics and imaging patterns of relapse and progression in patients with relapsed/refractory multiple myeloma: a pilot study utilizing 18F-FDG PET/CT},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {9},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12092399},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211157},
  year      = {2020},
  abstract  = {Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1-10) lines of therapy. Six (25\%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUV\(_{max}\)) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUV\(_{max}\) of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUV\(_{max}\) of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUV\(_{max}\) on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point.},
  language  = {en}
}
@article{ZhouDierksKertelsetal.2020,
  author    = {Zhou, Xiang and Dierks, Alexander and Kertels, Olivia and Kircher, Malte and Schirbel, Andreas and Samnick, Samuel and Buck, Andreas K. and Knorz, Sebastian and B{\"o}ckle, David and Scheller, Lukas and Messerschmidt, Janin and Barakat, Mohammad and Kort{\"u}m, K. Martin and Rasche, Leo and Einsele, Hermann and Lapa, Constantin},
  title     = {18F-FDG, 11C-Methionine, and 68Ga-Pentixafor PET/CT in patients with smoldering multiple myeloma: imaging pattern and clinical features},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {8},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12082333},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211240},
  year      = {2020},
  abstract  = {This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUV\(_{mean}\)) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUV\(_{mean}\) of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBR\(_{mean}\)) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBR\(_{mean}\) in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBR\(_{max}\) of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM.},
  language  = {en}
}
@phdthesis{Zeilmann2020,
  author    = {Zeilmann, Ute},
  title     = {Theologie und Exegese der Gottesknechtslieder. Der Beitrag der Gottesknechtslieder im biblischen Diskurs zum Thema Heilsuniversalismus und Theodizee-Problem},
  doi       = {10.25972/OPUS-20281},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202812},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die Gottesknechtslieder geh{\"o}ren zu den Texten des Alten Testaments, die sehr h{\"a}ufig interpretiert worden sind. Das liegt zweifelsohne an der besonderen christlichen Rezeption, aber auch an der literaturgeschichtlichen und theologischen Bedeutung der Kapitel Jes 40-55. Eine weitere Studie dazu k{\"o}nnte in der Tat als Zeit- und Ressourcenverschwendung gewertet werden, w{\"a}re da nicht die theologisch herausragende Bedeutung der Gottesknechtslieder {\"u}ber den literarischen Horizont Deuterojesaja hinaus. Sp{\"a}testens seit den Arbeiten von Ulrich Berges steht die lange Zeit angenommene Eigenst{\"a}ndigkeit der Textgruppe Gottesknechtslieder in Frage. Diese Sichtweise er{\"o}ffnet einerseits die M{\"o}glichkeit, die Funktionalit{\"a}t der Lieder innerhalb Deuterojesajas neu zu beschreiben, andererseits vernachl{\"a}ssigt sie eine genauere Beschreibung der Funktion des Gottesknechts im historischen Kontext des zu Ende gehenden babylonischen Exils. Diese Arbeit versucht mit den Methoden der historisch-kritischen Exegese zu rekonstruieren, wie eine prophetische Figur vom exilierten Teil Israels erwartet, als Gottesknecht zu wirken, aber zur Kenntnis nehmen muss, dass ihre Zeitgenossen dazu nicht bereit sind. Nach ihrem Scheitern, das in den Gottesknechtslieder verarbeitet ist, wird das prophetische Tun dieser Figur allerdings als Verwirklichung des Knechtsauftrags gedeutet. Die Besonderheit dieser Deutung des Knechtsauftrags im Kontext des Werkes Jes 40-55 liegt in seiner Erkl{\"a}rung des Leidens des Knechts: Der Knecht leidet wegen der Vergehen seiner Zeitgenossen. Innerhalb des alttestamentlichen Diskurses zum Problem der Theodizee liegt somit das Modell einer synchronen Schuldverkettung vor. Diese Bedeutung, die dem Tod des Knechts zugeschrieben wird, f{\"u}hrt sogar im klassischen Tun-Ergehen-Zusammenhang zur Vorstellung eines guten Ergehens des Knechts im Jenseits. Die erste Vorstellung von Auferstehung kann somit im 4. Gottesknechtslied verortet werden. Die Besonderheit des Knechtsauftrags zeigt eine weitere bedeutende theologische Weichenstellung im Alten Testament: Der Knechtsauftrag beinhaltet die Etablierung der g{\"o}ttlichen Rechts- und Heilsordnung f{\"u}r alle Nationen, dessen Licht der Knecht ist. Die Gottesknechtslieder sind also auch unverzichtbarer Bestandteil in der Wende zur Vorstellung eines Heilsuniversalismus. Diese Arbeit bietet demzufolge nicht nur eine Synthese der wichtigsten Forschungsfragen in Bezug auf die Gottesknechtslieder, sondern beschreibt ausf{\"u}hrlich die Relevanz dieser Textzeugnisse innerhalb alttestamentlicher Theologie.},
  subject      = {Heilswille Gottes},
  language  = {de}
}
@article{ZamoJohnstonAttygalleetal.2020,
  author    = {Zam{\`o}, Alberto and Johnston, Peter and Attygalle, Ayoma D and Laurent, Camille and Arber, Daniel A and Fend, Falko},
  title     = {Aggressive B-cell lymphomas with a primary bone marrow presentation},
  series = {Histopathology},
  volume    = {77},
  journal   = {Histopathology},
  number    = {3},
  doi       = {10.1111/his.14124},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218327},
  pages     = {369 -- 379},
  year      = {2020},
  language  = {en}
}
@article{ZahranAlbohyKhaliletal.2020,
  author    = {Zahran, Eman Maher and Albohy, Amgad and Khalil, Amira and Ibrahim, Alyaa Hatem and Ahmed, Heba Ali and El-Hossary, Ebaa M. and Bringmann, Gerhard and Abdelmohsen, Usama Ramadan},
  title     = {Bioactivity Potential of Marine Natural Products from Scleractinia-Associated Microbes and In Silico Anti-SARS-COV-2 Evaluation},
  series = {Marine Drugs},
  volume    = {18},
  journal   = {Marine Drugs},
  number    = {12},
  issn      = {1660-3397},
  doi       = {10.3390/md18120645},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220041},
  year      = {2020},
  abstract  = {Marine organisms and their associated microbes are rich in diverse chemical leads. With the development of marine biotechnology, a considerable number of research activities are focused on marine bacteria and fungi-derived bioactive compounds. Marine bacteria and fungi are ranked on the top of the hierarchy of all organisms, as they are responsible for producing a wide range of bioactive secondary metabolites with possible pharmaceutical applications. Thus, they have the potential to provide future drugs against challenging diseases, such as cancer, a range of viral diseases, malaria, and inflammation. This review aims at describing the literature on secondary metabolites that have been obtained from Scleractinian-associated organisms including bacteria, fungi, and zooxanthellae, with full coverage of the period from 1982 to 2020, as well as illustrating their biological activities and structure activity relationship (SAR). Moreover, all these compounds were filtered based on ADME analysis to determine their physicochemical properties, and 15 compounds were selected. The selected compounds were virtually investigated for potential inhibition for SARS-CoV-2 targets using molecular docking studies. Promising potential results against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and methyltransferase (nsp16) are presented.},
  language  = {en}
}
@phdthesis{Yurdadogan2020,
  author    = {Yurdadogan, Tino},
  title     = {Endorganschaden und Gef{\"a}ßalter bei Patienten mit koronarer Herzkrankheit},
  doi       = {10.25972/OPUS-21846},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218469},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die nicht-invasive Gef{\"a}ßdiagnostik stellt einen wichtigen Pfeiler in der Pr{\"a}vention von Herz-Kreislauferkrankungen dar. W{\"a}hrend lange Zeit die sonographische Messung der cIMT, als morphologisches Korrelat der Gef{\"a}ßalterung, als Goldstandard galt, ist in den letzten Jahren in Gestalt der Pulswellenanalyse/PWV-Messung eine Technik weiterentwickelt worden, die, als funktionelles Korrelat der Gef{\"a}ßalterung, aufgrund der leichteren Durchf{\"u}hrbarkeit und geringerer Untersucherabh{\"a}ngigkeit und Kosten vielversprechend ist. So erlaubt die Messung der Pulswelle mittels gew{\"o}hnlicher Blutdruckmanschetten, genau wie die cIMT, die Berechnung des individuellen Gef{\"a}ßalters und die Diagnostik f{\"u}r das Vorliegen eines Endorganschadens der Blutgef{\"a}ße. Um die Messergebnisse der beiden Untersuchungen miteinander zu vergleichen, wurden beide in der EUROASPIRE-IV Studie an Patienten mit koronarer Herzkrankheit durchgef{\"u}hrt. Die Auswertung der Messergebnisse der mit dem Vascular Explorer durchgef{\"u}hrten Pulswellenanalyse/PWV-Messung ergab {\"u}berraschenderweise, dass die Mehrheit der herzkranken Patienten weder eine vaskul{\"a}re Voralterung noch einen Endorganschaden der Blutgef{\"a}ße aufweisen. Im Falle der cIMT-Messung war Gegenteiliges der Fall, was trotz der medikament{\"o}sen Therapie der Patienten so zu erwarten war. Weiterhin zeigte sich lediglich eine geringe Korrelation zwischen den Messergebnissen beider Untersuchungen. Die Determinanten der einzelnen Messwerte aus cIMT und Pulswellenanalyse/PWV-Messung waren deckungsgleich mit den in der Literatur beschriebenen Faktoren, wenn auch viele der sonst signifikanten Regressoren das Signifikanzniveau in unserer Auswertung nicht unterschritten. Eine Limitation der funktionellen Gef{\"a}ßdiagnostik liegt derzeit darin, dass die Messergebnisse stark von dem verwendeten Messger{\"a}t abh{\"a}ngen. Es liegen noch zu wenig Vergleichsstudien vor, um die Messergebnisse, speziell von neueren Ger{\"a}ten wie dem Vascular Explorer, auf andere zu {\"u}bertragen. Bei der Berechnung des Gef{\"a}ßalters sollten daher optimalerweise ger{\"a}tespezifische Normwerte vorliegen, was beim Vascular Explorer nicht der Fall ist. Gleiches gilt f{\"u}r die Verwendung des PWVcf-Grenzwerts f{\"u}r die Diagnose eines Endorganschadens der Blutgef{\"a}ße. Analog hat auch die Messung der cIMT gewisse Einschr{\"a}nkungen. So w{\"a}re eine weitere Standardisierung der Messorte (A. carotis communis vs Bulbus vs A. carotis interna), zwischen denen sich die durchschnittliche cIMT erheblich unterscheidet, sowie der Messparameter (Minimal- vs Maximal- vs Mittelwert) w{\"u}nschenswert. Die universelle Anwendung eines cIMT-Grenzwerts zur Diagnose eines Endorganschadens der Blutgef{\"a}ße ist daher kritisch zu sehen. Dies zeigt sich auch darin, dass in den neuesten Leitlinien der bislang geltende Grenzwert angezweifelt und kein aktuell g{\"u}ltiger Grenzwert mehr genannt wird. Wir interpretieren unsere Ergebnisse dahingehend, dass unsere Messung der cIMT die zu erwartende pathologische Gef{\"a}ßalterung bei Patienten mit koronarer Herzkrankheit besser widerspiegelt als die Messung der Pulswelle mit dem Vascular Explorer. Welche der beiden Untersuchungen hinsichtlich der prognostischen Wertigkeit {\"u}berlegen ist, muss im Rahmen von L{\"a}ngsschnittstudien gekl{\"a}rt werden.},
  subject      = {Arteriosklerose},
  language  = {de}
}
@article{YousefStrzalkowskaHillenkampetal.2020,
  author    = {Yousef, Yousef Al and Strzalkowska, Alicja and Hillenkamp, Jost and Rosentreter, Andr{\´e} and Loewen, Nils A.},
  title     = {Comparison of a second-generation trabecular bypass (iStent inject) to ab interno trabeculectomy (Trabectome) by exact matching},
  series = {Graefe's Archive for Clinical and Experimental Ophthalmology},
  volume    = {258},
  journal   = {Graefe's Archive for Clinical and Experimental Ophthalmology},
  issn      = {0721-832X},
  doi       = {10.1007/s00417-020-04933-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232613},
  pages     = {2775-2780},
  year      = {2020},
  abstract  = {Purpose To achieve a highly balanced comparison of trabecular bypass stenting (IS2, iStent inject) with ab interno trabeculectomy (T, Trabectome) by exact matching. Methods Fifty-three IS2 eyes were matched to 3446 T eyes. Patients were matched using exact matching by baseline intraocular pressure (IOP), the number of glaucoma medications, and glaucoma type, and using nearest neighbor matching by age. Individuals without a close match were excluded. All surgeries were combined with phacoemulsification. Results A total of 78 eyes (39 in each group) could be matched as exact pairs with a baseline IOP of 18.3 ± 5.1 mmHg and glaucoma medications of 2.7 ± 1.2 in each. IOP in IS2 was reduced to 14.6 ± 4.2 mmHg at 3 months and in T to a minimum of 13.1 ± 3.2 mmHg at 1 month. In IS2, IOP began to rise again at 6 months, eventually exceeding baseline. At 24 months, IOP in IS2 was 18.8 ± 9.0 mmHg and in T 14.2 ± 3.5 mmHg. IS2 had a higher average IOP than T at all postoperative visits (p < 0.05 at 1, 12, 18 months). Glaucoma medications decreased to 2.0 ± 1.5 in IS2 and to 1.5 ± 1.4 in T. Conclusion T resulted in a larger and sustained IOP reduction compared with IS2 where a rebound occurred after 6 months to slightly above preoperative values.},
  language  = {en}
}
@phdthesis{Yavarzadeh2020,
  author    = {Yavarzadeh, Faraz},
  title     = {Auftreten laryngealer Konstriktionsph{\"a}nomene in verschiedenen Vokalisationstypen der ersten 7 Lebensmonate bei S{\"a}uglingen ohne Lippen-Kiefer-Gaumen-Segelspalten},
  doi       = {10.25972/OPUS-21023},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-210231},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {In der vorliegenden Studie wurde untersucht, ob laryngeale Konstriktionsph{\"a}nomene regelhaft bei gesunden S{\"a}uglingen mit deutscher Umgebungssprache auftreten, ob es eine altersabh{\"a}ngige oder geschlechtsabh{\"a}ngige Entwicklung in der Auftrittsh{\"a}ufigkeit der Ph{\"a}nomene gibt und ob diese zus{\"a}tzlich durch den Vokalisationstyp beeinflusst wird. Dazu wurden hier vier typische Vokalisationstypen im vorsprachlichen Alter definiert: spontanes S{\"a}uglingsweinen vor einer Mahlzeit in zwei Auspr{\"a}gungsformen (Typ C und UC, letzterer als Typ weniger intensiven S{\"a}uglingsweinens) sowie Nichtschreivokalisationen in zwei Auspr{\"a}gungsformen (UB: {\"U}bergangslaut zwischen UC und silbenartigem Vokalisieren (BB)). In der vorliegenden Arbeit wurden solche Konstriktionsph{\"a}nomene untersucht, die in der medizinischen Fachliteratur h{\"a}ufig mit pathologischen Zust{\"a}nden der respiratorischen Regelung sowie Vokaltraktmalformationen bei S{\"a}uglingen mit Lippen-Kiefer-Gaumen-Segelspalten beschrieben werden. Es wurde hier untersucht, ob {\"a}hnliche Ph{\"a}nomene auch bei gesunden S{\"a}uglingen regelhaft auftreten. Dazu wurde in einem kombinierten L{\"a}ngs- und Querschnittsdesign eine deskriptive Analyse von 20.406 Einzelvokalisationen von 20 S{\"a}uglingen in den ersten sieben Lebensmonaten vorgenommen. Die Vokalisationen lagen anonymisiert im Zentrum f{\"u}r vorsprachliche Entwicklung \& Entwicklungsst{\"o}rungen an der Poliklinik f{\"u}r Kieferorthop{\"a}die des Universit{\"a}tsklinikums W{\"u}rzburg vor. Es handelt sich um eine explorative, retrospektive Analyse. Unter Verwendung von Frequenzspektren und Audiofiles wurden alle Einzelvokalisationen audio-visuell analysiert und drei Stufen mit unterschiedlicher Auspr{\"a}gung der Konstriktionen einsortiert (Kategorie 1 - 3; Kategorie 0 = keine Konstriktionen in der Vokalisation). Die Kategoriendefinition wurde vom Autor der vorliegenden Arbeit in einer Voruntersuchung erarbeitet und durch weitere Kodierer getestet und als geeignet befunden. Im Ergebnis der Arbeit konnte gezeigt werden, dass die hier untersuchten Konstriktionsph{\"a}nomene regelhaft bei allen gesunden S{\"a}uglingen im Untersuchungszeitraum vorkommen. Die Auftrittsh{\"a}ufigkeit war dabei teilweise vom Geschlecht, vom Alter und vom Vokalisationstyp abh{\"a}ngig. Eine vergleichbare systematische Analyse lag bisher in der Literatur nicht vor. Die Ergebnisse werden aus physiologischer und linguistisch-phonetischer Perspektive interpretiert. Es konnte gezeigt werden, dass die im spontanen Weinen beobachteten Konstriktionsph{\"a}nomene auch bei den Komfortvokalisationen (Nichtschreivokalisationen) vorkamen. Dies st{\"u}tzt die Kontinuit{\"a}tshypothese in der vorsprachlichen Entwicklung. Die Arbeit hat auch widerlegt, dass alle Konstriktionsph{\"a}nomene im S{\"a}uglingsweinen ein Pathologiemarker sind. Die Differenzierung zwischen physiologischen und pathologischen Konstriktionsph{\"a}nomenen, die z.B. durch respiratorische Dysfunktion entstehen k{\"o}nnen (Stridor), ist eine Aufgabe f{\"u}r nachfolgende Arbeiten. F{\"u}r weiterf{\"u}hrende Arbeiten mit dem Ziel der Anwendung von Stimmregisterph{\"a}nomenen in der Vorsprachlichen Diagnostik sind methodisch erweiterte Ans{\"a}tze bei gleichzeitig gr{\"o}ßerer Stichprobe erforderlich.},
  subject      = {Vorprachliche Entwicklung},
  language  = {de}
}
@article{YangHeydarianKozjakPavlovicetal.2020,
  author    = {Yang, Tao and Heydarian, Motaharehsadat and Kozjak-Pavlovic, Vera and Urban, Manuela and Harbottle, Richard P. and Rudel, Thomas},
  title     = {Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {10},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  number    = {422},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2020.00422},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211372},
  year      = {2020},
  abstract  = {Neisseria gonorrhoeae, a Gram-negative obligate human pathogenic bacterium, infects human epithelial cells and causes sexually transmitted diseases. Emerging multi-antibiotic resistant gonococci and increasing numbers of infections complicate the treatment of infected patients. Here, we used an shRNA library screen and next-generation sequencing to identify factors involved in epithelial cell infection. Folliculin (FLCN), a 64 kDa protein with a tumor repressor function was identified as a novel host factor important for N. gonorrhoeae survival after uptake. We further determined that FLCN did not affect N. gonorrhoeae adherence and invasion but was essential for its survival in the cells by modulating autophagy. In addition, FLCN was also required to maintain cell to cell contacts in the epithelial layer. In an infection model with polarized cells, FLCN inhibited the polarized localization of E-cadherin and the transcytosis of gonococci across polarized epithelial cells. In conclusion, we demonstrate here the connection between FLCN and bacterial infection and in particular the role of FLCN in the intracellular survival and transcytosis of gonococci across polarized epithelial cell layers.},
  language  = {en}
}
@phdthesis{Yang2020,
  author    = {Yang, Manli},
  title     = {\(Chlamydia\) \(trachomatis\) metabolism during infection and metatranscriptome analysis in \(Neisseria\) \(gonorrhoeae\) coinfected STD patients},
  doi       = {10.25972/OPUS-18499},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184993},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Chlamydia trachomatis (Ct) is an obligate intracellular human pathogen. It causes blinding trachoma and sexually transmitted disease such as chlamydia, pelvic inflammatory disease and lymphogranuloma venereum. Ct has a unique biphasic development cycle and replicates in an intracellular vacuole called inclusion. Normally it has two forms: the infectious form, elementary body (EB); and the non-infectious form, reticulate body (RB). Ct is not easily amenable to genetic manipulation. Hence, to understand the infection process, it is crucial to study how the metabolic activity of Ct exactly evolves in the host cell and what roles of EB and RB play differentially in Ct metabolism during infection. In addition, Ct was found regularly coinfected with other pathogens in patients who got sexually transmitted diseases (STDs). A lack of powerful methods to culture Ct outside of the host cell makes the detailed molecular mechanisms of coinfection difficult to study. In this work, a genome-scale metabolic model with 321 metabolites and 277 reactions was first reconstructed by me to study Ct metabolic adaptation in the host cell during infection. This model was calculated to yield 84 extreme pathways, and metabolic flux strength was then modelled regarding 20hpi, 40hpi and later based on a published proteomics dataset. Activities of key enzymes involved in target pathways were further validated by RT-qPCR in both HeLa229 and HUVEC cell lines. This study suggests that Ct's major active pathways involve glycolysis, gluconeogenesis, glycerolphospholipid biosynthesis and pentose phosphate pathway, while Ct's incomplete tricarboxylic acid cycle and fatty acid biosynthesis are less active. EB is more activated in almost all these carbohydrate pathways than RB. Result suggests the survival of Ct generally requires a lot of acetyl-CoA from the host. Besides, both EB and RB can utilize folate biosynthesis to generate NAD(P)H but may use different pathways depending on the demands of ATP. When more ATP is available from both host cell and Ct itself, RB is more activated by utilizing energy providing chemicals generated by enzymes associated in the nucleic acid metabolism. The forming of folate also suggests large glutamate consumption, which is supposed to be converted from glutamine by the glutamine-fructose-6-phosphate transaminase (glmS) and CTP synthase (pyrG). Then, RNA sequencing (RNA-seq) data analysis was performed by me in a coinfection study. Metatranscriptome from patient RNA-seq data provides a realistic overview. Thirteen patient samples were collected and sequenced by our collaborators. Six male samples were obtained by urethral swab, and seven female samples were collected by cervicovaginal lavage. All the samples were Neisseria gonorrhoeae (GC) positive, and half of them had coinfection with Ct. HISAT2 and Stringtie were used for transcriptomic mapping and assembly respectively, and differential expression analysis by DESeq2, Ballgown and Cuffdiff2 are parallelly processed for comparison. Although the measured transcripts were not sufficient to assemble Ct's transcriptome, the differential expression of genes in both the host and GC were analyzed by comparing Ct positive group (Ct+) against Ct-uninfected group. The results show that in the Ct+ group, the host MHC class II immune response was highly induced. Ct infection is associated with the regulation of DNA methylation, DNA double-strand damage and ubiquitination. The analysis also shows Ct infection enhances host fatty acid beta oxidation, thereby inducing mROS, and the host responds to reduce ceramide production and glycolysis. The coinfection upregulates GC's own ion transporters and amino acid uptake, while it downregulates GC's restriction and modification systems. Meanwhile, GC has the nitrosative and oxidative stress response and also increases the ability for ferric uptake especially in the Ct+ group compared to Ct-uninfected group. In conclusion, methods in bioinformatics were used here in analyzing the metabolism of Ct itself, and the responses of the host and GC respectively in a coinfection study with and without Ct. These methods provide metabolic and metatranscriptomic details to study Ct metabolism during infection and Ct associated coinfection in the human microbiota.},
  subject      = {chlamydia trachomatis},
  language  = {en}
}
@article{WoersdoerferIAsahinaetal.2020,
  author    = {W{\"o}rsd{\"o}rfer, Philipp and I, Takashi and Asahina, Izumi and Sumita, Yoshinori and Erg{\"u}n, S{\"u}leyman},
  title     = {Do not keep it simple: recent advances in the generation of complex organoids},
  series = {Journal of Neural Transmission},
  volume    = {127},
  journal   = {Journal of Neural Transmission},
  issn      = {0300-9564},
  doi       = {10.1007/s00702-020-02198-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235628},
  pages     = {1569-1577},
  year      = {2020},
  abstract  = {3D cell culture models which closely resemble real human tissues are of high interest for disease modelling, drug screening as well as a deeper understanding of human developmental biology. Such structures are termed organoids. Within the last years, several human organoid models were described. These are usually stem cell derived, arise by self-organization, mimic mechanisms of normal tissue development, show typical organ morphogenesis and recapitulate at least some organ specific functions. Many tissues have been reproduced in vitro such as gut, liver, lung, kidney and brain. The resulting entities can be either derived from an adult stem cell population, or generated from pluripotent stem cells using a specific differentiation protocol. However, many organoid models only recapitulate the organs parenchyma but are devoid of stromal components such as blood vessels, connective tissue and inflammatory cells. Recent studies show that the incorporation of endothelial and mesenchymal cells into organoids improved their maturation and might be required to create fully functional micro-tissues, which will allow deeper insights into human embryogenesis as well as disease development and progression. In this review article, we will summarize and discuss recent works trying to incorporate stromal components into organoids, with a special focus on neural organoid models.},
  language  = {en}
}
@article{WoelfelSaetteleZechmeisteretal.2020,
  author    = {W{\"o}lfel, Angela and S{\"a}ttele, Mathias and Zechmeister, Christina and Nikolaev, Viacheslov O. and Lohse, Martin J. and Boege, Fritz and Jahns, Roland and Boivin-Jahns, Val{\´e}rie},
  title     = {Unmasking features of the auto-epitope essential for β\(_1\)-adrenoceptor activation by autoantibodies in chronic heart failure},
  series = {ESC Heart Failure},
  volume    = {7},
  journal   = {ESC Heart Failure},
  number    = {4},
  doi       = {10.1002/ehf2.12747},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235974},
  pages     = {1830-1841},
  year      = {2020},
  abstract  = {Aims Chronic heart failure (CHF) can be caused by autoantibodies stimulating the heart via binding to first and/or second extracellular loops of cardiac β1-adrenoceptors. Allosteric receptor activation depends on conformational features of the autoantibody binding site. Elucidating these features will pave the way for the development of specific diagnostics and therapeutics. Our aim was (i) to fine-map the conformational epitope within the second extracellular loop of the human β\(_1\)-adrenoceptor (β1ECII) that is targeted by stimulating β\(_1\)-receptor (auto)antibodies and (ii) to generate competitive cyclopeptide inhibitors of allosteric receptor activation, which faithfully conserve the conformational auto-epitope. Methods and results Non-conserved amino acids within the β\(_1\)EC\(_{II}\) loop (compared with the amino acids constituting the ECII loop of the β\(_2\)-adrenoceptor) were one by one replaced with alanine; potential intra-loop disulfide bridges were probed by cysteine-serine exchanges. Effects on antibody binding and allosteric receptor activation were assessed (i) by (auto)antibody neutralization using cyclopeptides mimicking β1ECII ± the above replacements, and (ii) by (auto)antibody stimulation of human β\(_1\)-adrenoceptors bearing corresponding point mutations. With the use of stimulating β\(_1\)-receptor (auto)antibodies raised in mice, rats, or rabbits and isolated from exemplary dilated cardiomyopathy patients, our series of experiments unmasked two features of the β\(_1\)EC\(_{II}\) loop essential for (auto)antibody binding and allosteric receptor activation: (i) the NDPK\(^{211-214}\) motif and (ii) the intra-loop disulfide bond C\(^{209}\)↔C\(^{215}\). Of note, aberrant intra-loop disulfide bond C\(^{209}\)↔C\(^{216}\) almost fully disrupted the functional auto-epitope in cyclopeptides. Conclusions The conformational auto-epitope targeted by cardio-pathogenic β\(_1\)-receptor autoantibodies is faithfully conserved in cyclopeptide homologues of the β\(_1\)EC\(_{II}\) loop bearing the NDPK\(^{211-214}\) motif and the C\(^{209}\)↔C\(^{215}\) bridge while lacking cysteine C216. Such molecules provide promising tools for novel diagnostic and therapeutic approaches in β\(_1\)-autoantibodypositive CHF.},
  language  = {en}
}
@phdthesis{Waeldchen2020,
  author    = {W{\"a}ldchen, Sina},
  title     = {Super-Resolution-Mikroskopie zur Visualisierung und Quantifizierung von Glutamatrezeptoren und ADHS-assoziierten Proteinen},
  doi       = {10.25972/OPUS-19283},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192834},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die Entwicklung hochaufl{\"o}sender Fluoreszenzmikroskopiemethoden hat die Lichtmikroskopie revolutioniert. Einerseits erm{\"o}glicht die h{\"o}here erzielte r{\"a}umliche Aufl{\"o}sung die Abbildung von Strukturen, die deutlich unterhalb der beugungsbedingten Aufl{\"o}sungsgrenze liegen. Andererseits erh{\"a}lt man durch Einzelmolek{\"u}llokalisationsmikroskopiemethoden wie dSTORM (Direct Stochastic Optical Reconstruction Microscopy) Informationen, welche man f{\"u}r quantitative Analysen heranziehen kann. Aufgrund der sich dadurch bietenden neuen M{\"o}glichkeiten, hat sich die hochaufl{\"o}sende Fluoreszenzmikroskopie rasant entwickelt und kommt mittlerweile zur Untersuchung einer Vielzahl biologischer und medizinischer Fragestellungen zum Einsatz. Trotz dieses Erfolgs ist jedoch nicht zu verleugnen, dass auch diese neuen Methoden ihre Nachteile haben. Dazu z{\"a}hlt die Notwendigkeit relativ hoher Laserleistungen, welche Voraussetzung f{\"u}r hohe Aufl{\"o}sung ist und bei lebenden Proben zur Photosch{\"a}digung f{\"u}hren kann. Diese Arbeit widmet sich sowohl dem Thema der Photosch{\"a}digung durch Einzelmolek{\"u}llokalisationsmikroskopie, als auch der Anwendung von dSTORM und SIM (Structured Illumination Microscopy) zur Untersuchung neurobiologischer Fragestellungen auf Proteinebene. Zur Ermittlung der Photosch{\"a}digung wurden lebende Zellen unter typischen Bedingungen bestrahlt und anschließend f{\"u}r 20-24 h beobachtet. Als quantitatives Maß f{\"u}r den Grad der Photosch{\"a}digung wurde der Anteil sterbender Zellen bestimmt. Neben der zu erwartenden Intensit{\"a}ts- und Wellenl{\"a}ngenabh{\"a}ngigkeit, zeigte sich, dass die Schwere der Photosch{\"a}digung auch von vielen weiteren Faktoren abh{\"a}ngt und dass sich Einzelmolek{\"u}llokalisationsmikroskopie bei Ber{\"u}cksichtigung der gewonnenen Erkenntnisse durchaus mit Lebendzellexperimenten vereinbaren l{\"a}sst. Ein weiteres Projekt diente der Untersuchung der A- und B-Typ-Glutamatrezeptoren an der neuromuskul{\"a}ren Synapse von Drosophila melanogaster mittels dSTORM. Dabei konnte eine ver{\"a}nderte Anordnung beider Rezeptortypen infolge synaptischer Plastizit{\"a}t beobachtet, sowie eine absolute Quantifizierung des A-Typ-Rezeptors durchgef{\"u}hrt werden. Im Mittelpunkt eines dritten Projekts standen Cadherin-13 (CDH13) sowie der Glucosetransporter Typ 3 (GluT3), welche beide mit der Aufmerksamkeitsdefizit-Hyperaktivit{\"a}tsst{\"o}rung in Verbindung gebracht werden. CDH13 konnte mittels SIM in serotonergen Neuronen, sowie radi{\"a}ren Gliazellen der dorsalen Raphekerne des embryonalen Mausgehirns nachgewiesen werden. Die Rolle von GluT3 wurde in aus induzierten pluripotenten Stammzellen differenzierten Neuronen analysiert, welche verschiedene Kopienzahlvariation des f{\"u}r GluT3-codierenden SLC2A3-Gens aufwiesen. Die Proteine GluT3, Bassoon und Homer wurden mittels dSTORM relativ quantifiziert. W{\"a}hrend die Deletion des Gens zu einer erwartenden Verminderung von GluT3 auf Proteinebene f{\"u}hrte, hatte die Duplikation keinen Effekt auf die GluT3-Menge. F{\"u}r Bassoon und Homer zeigte sich weder durch die Deletion noch die Duplikation eine signifikante Ver{\"a}nderung.},
  subject      = {Mikroskopie},
  language  = {de}
}
@phdthesis{Waeldchen2020,
  author    = {W{\"a}ldchen, Felix},
  title     = {3D Single Molecule Imaging In Whole Cells Enabled By Lattice Light-Sheet Illumination},
  doi       = {10.25972/OPUS-20711},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207111},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Single molecule localization microscopy has seen a remarkable growth since its first experimental implementations about a decade ago. Despite its technical challenges, it is already widely used in medicine and biology and is valued as a unique tool to gain molecular information with high specificity. However, common illumination techniques do not allow the use of single molecule sensitive super-resolution microscopy techniques such as direct stochastic optical reconstruction microscopy (dSTORM) for whole cell imaging. In addition, they can potentially alter the quantitative information. In this thesis, I combine dSTORM imaging in three dimensions with lattice lightsheet illumination to gain quantitative molecular information from cells unperturbed by the illumination and cover slip effects. Lattice light-sheet illumination uses optical lattices for beam shaping to restrict the illumination to the detectable volume. I describe the theoretical background needed for both techniques and detail the experimental realization of the system as well as the software that I developed to efficiently evaluate the data. Eventually, I will present key datasets that demonstrate the capabilities of the developed microscope system with and without dSTORM. My main goal here was to use these techniques for imaging the neural cell adhesion molecule (NCAM, also known as CD56) in whole cells. NCAM is a plasma membrane receptor known to play a key role in biological processes such as memory and learning. Combining dSTORM and lattice light-sheet illumination enables the collection of quantitative data of the distribution of molecules across the whole plasma membrane, and shows an accumulation of NCAM at cell-cell interfaces. The low phototoxicity of lattice light-sheet illumination further allows for tracking individual NCAM dimers in living cells, showing a significant dependence of its mobility on the actin skeleton of the cell.},
  subject      = {Einzelmolek{\"u}lmikroskopie},
  language  = {en}
}
@article{WurmbScholtesKolibayetal.2020,
  author    = {Wurmb, Thomas and Scholtes, Katja and Kolibay, Felix and Schorscher, Nora and Ertl, Georg and Ernestus, Ralf-Ingo and Vogel, Ulrich and Franke, Axel and Kowalzik, Barbara},
  title     = {Hospital preparedness for mass critical care during SARS-CoV-2 pandemic},
  series = {Critical Care},
  volume    = {24},
  journal   = {Critical Care},
  doi       = {10.1186/s13054-020-03104-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230201},
  year      = {2020},
  abstract  = {Mass critical care caused by the severe acute respiratory syndrome corona virus 2 pandemic poses an extreme challenge to hospitals. The primary goal of hospital disaster preparedness and response is to maintain conventional or contingency care for as long as possible. Crisis care must be delayed as long as possible by appropriate measures. Increasing the intensive care unit (ICU) capacities is essential. In order to adjust surge capacity, the reduction of planned, elective patient care is an adequate response. However, this involves numerous problems that must be solved with a sense of proportion. This paper summarises preparedness and response measures recommended to acute care hospitals.},
  language  = {en}
}
@article{WurmbFrankeSchorscheretal.2020,
  author    = {Wurmb, Thomas and Franke, Axel and Schorscher, Nora and Kowalzik, Barbara and Helm, Matthias and Bohnen, Renate and Helmerichs, Jutta and Grueneisen, Ulrich and Cwojdzinski, Detlef and Jung, Georg and L{\"u}cking, Gesa and Weber, Martin},
  title     = {Emergency response to terrorist attacks: results of the federal-conducted evaluation process in Germany},
  series = {European Journal of Trauma and Emergency Surgery},
  volume    = {46},
  journal   = {European Journal of Trauma and Emergency Surgery},
  issn      = {1863-9933},
  doi       = {10.1007/s00068-020-01347-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231777},
  pages     = {725-730},
  year      = {2020},
  abstract  = {Purpose Rescue missions during terrorist attacks are extremely challenging for all rescue forces (police as well as non-police forces) involved. To improve the quality and safety of the rescue missions during an active killing event, it is obligatory to adapt common rescue mission goals and strategies. Methods After the recent attacks in Europe, the Federal Office of Civil Protection and Disaster Assistance started an evaluation process on behalf of the Federal Ministry of the Interior and the Federal Ministry of Health. This was done to identify weaknesses, lessons learned and to formulate new adapted guidelines. Results The presented bullet point recommendations summarise the basic and most important results of the ongoing evaluation process for the Federal Republic of Germany. The safety of all the rescue forces and survival of the greatest possible number of casualties are the priority goals. Furthermore, the preservation and re-establishment of the socio-political integrity are the overarching goals of the management of active killing events. Strategic incident priorities are to stop the killing and to save as much lives as possible. The early identification and prioritised transportation of casualties with life-threatening non-controllable bleeding are major tasks and the shortest possible on-scene time is an important requirement with respect to safety issues. Conclusion With respect to hazard prevention tactics within Germany, we attributed the highest priority impact to the bullet points. The focus of the process has now shifted to intense work about possible solutions for the identified deficits and implementation strategies of such solutions during mass killing incidents.},
  language  = {en}
}
@article{WolfBrandstetterBeutnerHessetal.2020,
  author    = {Wolf-Brandstetter, C and Beutner, R and Hess, R and Bierbaum, S and Wagner, K and Scharnweber, D and Gbureck, U and Moseke, C},
  title     = {Multifunctional calcium phosphate based coatings on titanium implants with integrated trace elements},
  series = {Biomedical Materials},
  volume    = {15},
  journal   = {Biomedical Materials},
  number    = {2},
  doi       = {10.1088/1748-605X/ab5d7b},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254085},
  year      = {2020},
  abstract  = {For decades, the main focus of titanium implants developed to restore bone functionality was on improved osseointegration. Additional antimicrobial properties have now become desirable, due to the risk that rising antibiotic resistance poses for implant-associated infections. To this end, the trace elements of copper and zinc were integrated into calcium phosphate based coatings by electrochemically assisted deposition. In addition to their antimicrobial activity, zinc is reported to attract bone progenitor cells through chemotaxis and thus increase osteogenic differentiation, and copper to stimulate angiogenesis. Quantities of up to 68.9 ± 0.1 μg cm\(^{-2}\) of copper and 56.6 ± 0.4 μg cm\(^{-2}\) of zinc were deposited; co-deposition of both ions did not influence the amount of zinc but slightly increased the amount of copper in the coatings. The release of deposited copper and zinc species was negligible in serum-free simulated body fluid. In protein-containing solutions, a burst release of up to 10 μg ml\(^{-1}\) was observed for copper, while zinc was released continuously for up to 14 days. The presence of zinc was beneficial for adhesion and growth of human mesenchymal stromal cells in a concentration-dependent manner, but cytotoxic effects were already visible for coatings with an intermediate copper content. However, co-deposited zinc could somewhat alleviate the adverse effects of copper. Antimicrobial tests with E. coli revealed a decrease in adherent bacteria on brushite without copper or zinc of 60\%, but if the coating contained both ions there was almost no bacterial adhesion after 12 h. Coatings with high zinc content and intermediate copper content had the overall best multifunctional properties.},
  language  = {en}
}
@phdthesis{Woidich2020,
  author    = {Woidich, Anna},
  title     = {Funktionstests zur Detektion von chronischen Sprunggelenkinstabilit{\"a}ten},
  doi       = {10.25972/OPUS-19931},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199318},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Bei Sportlern aber auch bei Nichtsportlern mit Bandl{\"a}sionen im Bereich des Sprunggelenks ist die Bestimmung des Zeitpunktes der Wiederaufnahme sportlicher Aktivit{\"a}t von entscheidender Bedeutung - insbesondere um m{\"o}glichen Folgeverletzungen in der Zukunft vorzubeugen. Zur Beurteilung des richtigen Zeitpunkts z{\"a}hlt die Beurteilung der sportlichen Leistungsf{\"a}higkeit zu den wichtigsten Faktoren. Um diese Beurteilung vorzunehmen, ist das Vorhandensein von Referenzwerten f{\"u}r eine geeignete Testbatterie n{\"o}tig. Mit Hilfe der Ergebnisse dieser Arbeit sowie der gew{\"a}hlten Art der Darstellung kann so die Leistungsf{\"a}higkeit eines Probanden, welcher sich nicht im akuten Stadium einer Verletzung oder der direkt daran anschließenden Rekonvaleszens befindet, nach einer vorangegangenen Verletzung im Bereich des Sprunggelenks beurteilt werden. Ein ad{\"a}quater Zeitpunkt zum {\"U}bergang von der Phase „Return to sports" zu „Return to play" beziehungsweise „Return to competition" ohne das Risiko einer erneuten Verletzung kann so besser abgesch{\"a}tzt werden.},
  subject      = {Sprunggelenkverletzung},
  language  = {de}
}
@unpublished{WohlgemuthMitric2020,
  author    = {Wohlgemuth, Matthias and Mitric, Roland},
  title     = {Excitation energy transport in DNA modelled by multi-chromophoric field-induced surface hopping},
  series = {Physical Chemistry Chemical Physics},
  journal   = {Physical Chemistry Chemical Physics},
  edition   = {submitted version},
  doi       = {10.1039/D0CP02255A},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-209467},
  year      = {2020},
  abstract  = {Absorption of ultraviolet light is known as a major source of carcinogenic mutations of DNA. The underlying processes of excitation energy dissipation are yet not fully understood. In this work we provide a new and generally applicable route for studying the excitation energy transport in multi-chromophoric complexes at an atomistic level. The surface-hopping approach in the frame of the extended Frenkel exciton model combined with QM/MM techniques allowed us to simulate the photodynamics of the alternating (dAdT)10 : (dAdT)10 double-stranded DNA. In accordance with recent experiments, we find that the excited state decay is multiexponential, involving a long and a short component which are due to two distinct mechanisms: formation of long-lived delocalized excitonic and charge transfer states vs. ultrafast decaying localized states resembling those of the bare nucleobases. Our simulations explain all stages of the ultrafast photodynamics including initial photoexcitation, dynamical evolution out of the Franck-Condon region, excimer formation and nonradiative relaxation to the ground state.},
  language  = {en}
}
@phdthesis{Witzinger2020,
  author    = {Witzinger, Linda},
  title     = {Rolle der Pyridoxal 5´-Phosphat Phosphatase PDXP im Vitamin B6-Metabolismus muriner Erythrozyten und Hippocampi},
  doi       = {10.25972/OPUS-21654},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216546},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die Phosphatase PDXP (auch bekannt als Chronophin) geh{\"o}rt zur Familie der HAD Phosphatasen, einer ubiquit{\"a}r exprimierten Enzymklasse mit wichtigen physiologischen Funktionen. PDXP zeigt Phosphatase-Aktivit{\"a}t gegen{\"u}ber seinem Substrat Pyridoxal 5´-Phosphat (PLP), der aktivierten Form von Vitamin B6. PDXP-defiziente M{\"a}use (Knockout-M{\"a}use) weisen im Vergleich zu Wildtypen verdoppelte PLP-Konzentrationen in Erythrozyten sowie im Gesamthirn auf. Vermutlich kommt PDXP daher eine wichtige Funktion in Erythrozyten und im Hirn zu. Ziel dieser Arbeit war es, erste Einblicke in diese Funktion(en) von PDXP zu erlangen. Hierzu wurden HPLC-basierte Analysen der erythrozyt{\"a}ren PLP-Konzentrationen in Wildtyp- sowie PDXP-defizienten M{\"a}usen durchgef{\"u}hrt. Dabei ließen sich die rund doppelt so hohen erythrozyt{\"a}ren PLP-Level in den KO-M{\"a}usen best{\"a}tigen. Zudem ist es gelungen, eine Methode zur Messung der endogenen Phosphatase-Aktivit{\"a}t von PDXP in Erythrozytenlysaten zu etablieren. So konnte im Wildtyp anhand der Verringerung der PLP-Konzentrationen pro Zeiteinheit eine erythrozyt{\"a}re PDXP-Aktivit{\"a}t nachgewiesen werden. Dazu waren die Inkubation mit Pyridoxin, sowie die Anwendung eines Inhibitors der PDXK notwendig. Eine bis dato vermutete Funktion der PDXP, zur Mobilisation von erythrozyt{\"a}rem PLP w{\"a}hrend Fastenzeiten, konnte ausgeschlossen werden. So zeigte der Vergleich der erythrozyt{\"a}ren PLP-Konzentrationen aus gefasteten mit normal gef{\"u}tterten Tieren in beiden Genotypen exakt dieselbe prozentuale PLP-Verringerung. W{\"a}hrend Nahrungszufuhr ließ sich jedoch eine Funktion der Phosphatase PDXP als „Converter" von Pyridoxin zu Pyridoxal erkennen. Ausgehend von PN konnte im Wildtyp ({\"u}ber die Zwischenprodukte PNP und PLP) eine PDXP-abh{\"a}ngige Dephosphorylierung von PLP zu PL erfolgen. So wies der Wildtyp eine rund vierfach h{\"o}here PL-Produktion auf, verglichen mit der PDXP-defizienten Maus. Die Phosphatase PDXP erwies sich als essenziell f{\"u}r die erythrozyt{\"a}re Konversion von Pyridoxin zu Pyridoxal. Dadurch erreicht der Organismus eine metabolische Flexibilit{\"a}t, die ihn bis zu einem gewissen Grad unabh{\"a}ngig von der Nahrungsauswahl macht. Zudem k{\"o}nnen Zellen oder Organe, denen durch das Fehlen der PNPO, die Konversion zu PLP nicht m{\"o}glich ist, mit PL versorgt werden. Aus der hohen Reaktivit{\"a}t von PLP mit umliegenden Nucleophilen ergibt sich eine gewisse Problematik f{\"u}r die Zelle im Umgang mit freiem PLP. So liegt der Großteil des erythrozyt{\"a}ren PLPs gebunden an Proteine (vor allem H{\"a}moglobin) vor. Anhand von Filtern (MWCO, 3000) ließ sich zwischen der hier definiert als „freien" und der „gebundenen" Form von PLP differenzieren. So konnten erste Erkenntnisse zur Rolle von PDXP als Determinator freier PLP-Konzentrationen in Erythrozyten und insbesondere im Hippocampus erlangt werden. Im Hippocampus ergaben sich insgesamt deutlich h{\"o}here Konzentrationen an freiem PLP als in den Erythrozyten und es bestand zudem ein Unterschied zwischen den Genotypen. So wiesen die KO-M{\"a}use ~1/3 h{\"o}here freie PLP-Konzentrationen im Vergleich zu den Wildtypen auf. Schließlich konnte ein Effekt des Tieralters auf den PLP-Metabolismus festgestellt werden. Sowohl in den Erythrozyten als auch im Hippocampus ergaben sich alterskorrelierte {\"A}nderungen ihrer PLP-Konzentrationen. Zudem zeigten Western Blot Analysen altersbedingte Unterschiede ihrer Vitamin B6-Enzymexpressionen. So wiesen {\"a}ltere Wildtypen im Hippocampus eine f{\"u}nffach erh{\"o}hte PDXP-Expression verglichen mit j{\"u}ngeren Tieren auf. In den Erythrozytenlysaten hingegen zeigten {\"a}ltere Tiere beider Genotypen eine rund vierfach geringere PNPO-Expression gegen{\"u}ber j{\"u}ngeren Tieren. Die mit dem Alter eintretende physiologische Verringerung der erythrozyt{\"a}ren PNPO-Expression w{\"u}rde somit f{\"u}r den Organismus einen Verlust seiner metabolischen Flexibilit{\"a}t bedeuten, die mit der Konversion von PN zu PL einhergeht.},
  subject      = {Vitamin B6},
  language  = {de}
}
@book{Witzany2020,
  author    = {Witzany, Stefan},
  title     = {Macht Breakdance Kinder stark? Eine empirische Untersuchung zum Einfluss von Breakdance im Schulsport auf physische und psychosoziale Ressourcen},
  edition   = {1. Auflage},
  publisher = {W{\"u}rzburg University Press},
  address   = {W{\"u}rzburg},
  isbn      = {978-3-95826-136-5},
  doi       = {10.25972/WUP-978-3-95826-137-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198491},
  publisher      = {W{\"u}rzburg University Press},
  pages     = {196},
  year      = {2020},
  abstract  = {Fragestellung und Design Ziel der 6-monatigen Intervention Breakdance im Rahmen von Sport nach 1 war es, Ver{\"a}nderungen bei physischen und psychosozialen Parametern zu betrachten. In einem Kontrollgruppendesign mit drei Messzeitpunkten (t1, t2, t3) wurden quantitative Methoden (motorische Tests, schriftliche Befragung) im L{\"a}ngsschnitt und qualitative Verfahren (m{\"u}ndliche Befragung) im Querschnitt am Ende des Untersuchungszeitraums eingesetzt. Mittels standardisierter Frageb{\"o}gen wurden die Merkmale sportartspezifische- und allgemeine Selbstwirksamkeit sowie Kooperationsf{\"a}higkeit untersucht (Klein-Heßling et.al., 2003). Dar{\"u}ber hinaus wurde der deutsche Motoriktest (DMT6-18) durchgef{\"u}hrt, um die Entwicklung der Merkmale Kraftausdauer im Rumpf- und den oberen Extremit{\"a}ten, Schnellkraft in den Beinen, Koordination unter Pr{\"a}zisionsdruck sowie Koordination unter Zeitdruck zu betrachten. Ergebnisse und Diskussion Es zeigt sich, dass Kinder durch Breakdance ihre Koordination, insbesondere die Koordination unter Pr{\"a}zisionsdruck, Kraftleistungen, insbesondere die Schnellkraft in den Beinen, sowie die Kraftausdauer in den oberen Extremit{\"a}ten verbessern k{\"o}nnen. L{\"a}ngsschnittliche Wirkungen im psychosozialen Bereich zeigen sich bei der sportartspezifischen Selbstwirksamkeit sowie im zweiten Teil des Vergleichszeitraums (t2/t3) bez{\"u}glich der allgemeinen Selbstwirksamkeit . Die qualitativen Ergebnisse legen zudem nahe, dass Breakdance zu einer positiven Grundstimmung sowie zu gesteigerter Zuversicht und Leistungsfreude beitr{\"a}gt. Forschungsbedarf ergibt sich hinsichtlich der Frage der Nachhaltigkeit der Effekte und hinsichtlich der Spezifit{\"a}t des Settings.},
  subject      = {Breakdance},
  language  = {de}
}
@phdthesis{Wisheckel2020,
  author    = {Wisheckel, Florian},
  title     = {Some Applications of D-Norms to Probability and Statistics},
  doi       = {10.25972/OPUS-21214},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212140},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {This cumulative dissertation is organized as follows: After the introduction, the second chapter, based on "Asymptotic independence of bivariate order statistics" (2017) by Falk and Wisheckel, is an investigation of the asymptotic dependence behavior of the components of bivariate order statistics. We find that the two components of the order statistics become asymptotically independent for certain combinations of (sequences of) indices that are selected, and it turns out that no further assumptions on the dependence of the two components in the underlying sample are necessary. To establish this, an explicit representation of the conditional distribution of bivariate order statistics is derived. Chapter 3 is from "Conditional tail independence in archimedean copula models" (2019) by Falk, Padoan and Wisheckel and deals with the conditional distribution of an Archimedean copula, conditioned on one of its components. We show that its tails are independent under minor conditions on the generator function, even if the unconditional tails were dependent. The theoretical findings are underlined by a simulation study and can be generalized to Archimax copulas. "Generalized pareto copulas: A key to multivariate extremes" (2019) by Falk, Padoan and Wisheckel lead to Chapter 4 where we introduce a nonparametric approach to estimate the probability that a random vector exceeds a fixed threshold if it follows a Generalized Pareto copula. To this end, some theory underlying the concept of Generalized Pareto distributions is presented first, the estimation procedure is tested using a simulation and finally applied to a dataset of air pollution parameters in Milan, Italy, from 2002 until 2017. The fifth chapter collects some additional results on derivatives of D-norms, in particular a condition for the existence of directional derivatives, and multivariate spacings, specifically an explicit formula for the second-to-last bivariate spacing.},
  subject      = {Kopula <Mathematik>},
  language  = {en}
}
@article{WirthensohnFinze2020,
  author    = {Wirthensohn, Raphael and Finze, Maik},
  title     = {The crystal structure of trimethylsulfonium tris(trifluoromethylsulfonyl)methanide, C\(_7\)H\(_9\)F\(_9\)O\(_6\)S\(_4\)},
  series = {Zeitschrift f{\"u}r Kristallographie - New Crystal Structures},
  volume    = {236},
  journal   = {Zeitschrift f{\"u}r Kristallographie - New Crystal Structures},
  number    = {2},
  doi       = {10.1515/ncrs-2020-0612},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231358},
  pages     = {417-419},
  year      = {2020},
  abstract  = {C\(_7\)H\(_9\)F\(_9\)O\(_6\)S\(_4\), orthorhombic, P2\(_1\)2\(_1\)2\(_1\) (no. 19), a = 8.80180(10) {\AA}, b= 10.96580(10) {\AA}, c = 16.91360(10) {\AA},V= 1632.48(3) {\AA}\(^3\), Z= 4, R\(_{gt}\)(F) = 0.0222, wR\(_{ref}\)(F\(^2\)) = 0.0604, T = 100 K.},
  language  = {en}
}
@article{WirthFoersterKundeetal.2020,
  author    = {Wirth, Robert and Foerster, Anna and Kunde, Wilfried and Pfister, Roland},
  title     = {Design choices: Empirical recommendations for designing two-dimensional finger-tracking experiments},
  series = {Behavior Research Methods},
  volume    = {52},
  journal   = {Behavior Research Methods},
  doi       = {10.3758/s13428-020-01409-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235569},
  pages     = {2394-2416},
  year      = {2020},
  abstract  = {The continuous tracking of mouse or finger movements has become an increasingly popular research method for investigating cognitive and motivational processes such as decision-making, action-planning, and executive functions. In the present paper, we evaluate and discuss how apparently trivial design choices of researchers may impact participants' behavior and, consequently, a study's results. We first provide a thorough comparison of mouse- and finger-tracking setups on the basis of a Simon task. We then vary a comprehensive set of design factors, including spatial layout, movement extent, time of stimulus onset, size of the target areas, and hit detection in a finger-tracking variant of this task. We explore the impact of these variations on a broad spectrum of movement parameters that are typically used to describe movement trajectories. Based on our findings, we suggest several recommendations for best practice that avoid some of the pitfalls of the methodology. Keeping these recommendations in mind will allow for informed decisions when planning and conducting future tracking experiments.},
  language  = {en}
}
@article{WirschingOrtUeceyler2020,
  author    = {Wirsching, Isabelle and Ort, Nora and {\"U}{\c{c}}eyler, Nurcan},
  title     = {ALS or ALS mimic by neuroborreliosis — A case report},
  series = {Clinical Case Reports},
  volume    = {8},
  journal   = {Clinical Case Reports},
  doi       = {10.1002/ccr3.2569},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201308},
  pages     = {86-91},
  year      = {2020},
  abstract  = {Comprehensive investigation in motor neuron disease is vital not to miss a treatable differential diagnosis. Neuroborreliosis should be considered during an ALS work-up. However, false-positive CSF results do occur, and thus, results should be interpreted carefully in context of all clinical test results.},
  language  = {en}
}
@article{WinterPryssProbstetal.2020,
  author    = {Winter, Michael and Pryss, R{\"u}diger and Probst, Thomas and Reichert, Manfred},
  title     = {Towards the applicability of measuring the electrodermal activity in the context of process model comprehension: feasibility study},
  series = {Sensors},
  volume    = {20},
  journal   = {Sensors},
  number    = {16},
  issn      = {1424-8220},
  doi       = {10.3390/s20164561},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211276},
  year      = {2020},
  abstract  = {Process model comprehension is essential in order to understand the five Ws (i.e., who, what, where, when, and why) pertaining to the processes of organizations. However, research in this context showed that a proper comprehension of process models often poses a challenge in practice. For this reason, a vast body of research exists studying the factors having an influence on process model comprehension. In order to point research towards a neuro-centric perspective in this context, the paper at hand evaluates the appropriateness of measuring the electrodermal activity (EDA) during the comprehension of process models. Therefore, a preliminary test run and a feasibility study were conducted relying on an EDA and physical activity sensor to record the EDA during process model comprehension. The insights obtained from the feasibility study demonstrated that process model comprehension leads to an increased activity in the EDA. Furthermore, EDA-related results indicated significantly that participants were confronted with a higher cognitive load during the comprehension of complex process models. In addition, the experiences and limitations we learned in measuring the EDA during the comprehension of process models are discussed in this paper. In conclusion, the feasibility study demonstrated that the measurement of the EDA could be an appropriate method to obtain new insights into process model comprehension.},
  language  = {en}
}
@phdthesis{Winnerlein2020,
  author    = {Winnerlein, Martin},
  title     = {Molecular Beam Epitaxy and Characterization of the Magnetic Topological Insulator (V,Bi,Sb)\(_2\)Te\(_3\)},
  doi       = {10.25972/OPUS-21166},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211666},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {The subject of this thesis is the fabrication and characterization of magnetic topological insulator layers of (V,Bi,Sb)\(_2\)Te\(_3\) exhibiting the quantum anomalous Hall effect. A major task was the experimental realization of the quantum anomalous Hall effect, which is only observed in layers with very specific structural, electronic and magnetic properties. These properties and their influence on the quantum anomalous Hall effect are analyzed in detail. First, the optimal conditions for the growth of pure Bi\(_2\)Te\(_3\) and Sb\(_2\)Te\(_3\) crystal layers and the resulting structural quality are studied. The crystalline quality of Bi\(_2\)Te\(_3\) improves significantly at higher growth temperatures resulting in a small mosaicity-tilt and reduced twinning defects. The optimal growth temperature is determined as 260\(^{\circ}\)C, low enough to avoid desorption while maintaining a high crystalline quality. The crystalline quality of Sb\(_2\)Te\(_3\) is less dependent on the growth temperature. Temperatures below 230\(^{\circ}\)C are necessary to avoid significant material desorption, though. Especially for the nucleation on Si(111)-H, a low sticking coefficient is observed preventing the coalescence of islands into a homogeneous layer. The influence of the substrate type, miscut and annealing sequence on the growth of Bi\(_2\)Te\(_3\) layers is investigated. The alignment of the layer changes depending on the miscut angle and annealing sequence: Typically, layer planes align parallel to the Si(111) planes. This can enhance the twin suppression due to transfer of the stacking order from the substrate to the layer at step edges, but results in a step bunched layer morphology. For specific substrate preparations, however, the layer planes are observed to align parallel to the surface plane. This alignment avoids displacement at the step edges, which would cause anti-phase domains. This results in narrow Bragg peaks in XRD rocking curve scans due to long-range order in the absence of anti-phase domains. Furthermore, the use of rough Fe:InP(111):B substrates leads to a strong reduction of twinning defects and a significantly reduced mosaicity-twist due to the smaller lattice mismatch. Next, the magnetically doped mixed compound V\(_z\)(Bi\(_{1-x}\)Sb\(_x\))\(_{2-z}\)Te\(_3\) is studied in order to realize the quantum anomalous Hall effect. The addition of V and Bi to Sb\(_2\)Te\(_3\) leads to efficient nucleation on the Si(111)-H surface and a closed, homogeneous layer. Magneto-transport measurements of layers reveal a finite anomalous Hall resistivity significantly below the von Klitzing constant. The observation of the quantum anomalous Hall effect requires the complete suppression of parasitic bulklike conduction due to defect induced carriers. This can be achieved by optimizing the thickness, composition and growth conditions of the layers. The growth temperature is observed to strongly influence the structural quality. Elevated temperatures result in bigger islands, improved crystallographic orientation and reduced twinning. On the other hand, desorption of primarily Sb is observed, affecting the thickness, composition and reproducibility of the layers. At 190\(^{\circ}\)C, desorption is avoided enabling precise control of layer thickness and composition of the quaternary compound while maintaining a high structural quality. It is especially important to optimize the Bi/Sb ratio in the (V,Bi,Sb)\(_2\)Te\(_3\) layers, since by alloying n-type Bi\(_2\)Te\(_3\) and p-type Sb\(_2\)Te\(_3\) charge neutrality is achieved at a specific mixing ratio. This is necessary to shift the Fermi level into the magnetic exchange gap and fully suppress the bulk conduction. The Sb content x furthermore influences the in-plane lattice constant a significantly. This is utilized to accurately determine x even for thin films below 10 nm thickness required for the quantum anomalous Hall effect. Furthermore, x strongly influences the surface morphology: with increasing x the island size decreases and the RMS roughness increases by up to a factor of 4 between x = 0 and x = 1. A series of samples with x varied between 0.56-0.95 is grown, while carefully maintaining a constant thickness of 9 nm and a doping concentration of 2 at.\% V. Magneto-transport measurements reveal the charge neutral point around x = 0.86 at 4.2 K. The maximum of the anomalous Hall resistivity of 0.44 h/e\(^2\) is observed at x = 0.77 close to charge neutrality. Reducing the measurement temperature to 50 mK significantly increases the anomalous Hall resistivity. Several samples in a narrow range of x between 0.76-0.79 show the quantum anomalous Hall effect with the Hall resistivity reaching the von Klitzing constant and a vanishing longitudinal resistivity. Having realized the quantum anomalous Hall effect as the first group in Europe, this breakthrough enabled us to study the electronic and magnetic properties of the samples in close collaborations with other groups. In collaboration with the Physikalisch-Technische Bundesanstalt high-precision measurements were conducted with detailed error analysis yielding a relative de- viation from the von Klitzing constant of (0.17 \(\pm\) 0.25) * 10\(^{-6}\). This is published as the smallest, most precise value at that time, proving the high quality of the provided samples. This result paves the way for the application of magnetic topological insulators as zero-field resistance standards. Non-local magneto-transport measurements were conducted at 15 mK in close collaboration with the transport group in EP3. The results prove that transport happens through chiral edge channels. The detailed analysis of small anomalies in transport measurements reveals instabilities in the magnetic phase even at 15 mK. Their time dependent nature indicates the presence of superparamagnetic contributions in the nominally ferromagnetic phase. Next, the influence of the capping layer and the substrate type on structural properties and the impact on the quantum anomalous Hall effect is investigated. To this end, a layer was grown on a semi-insulating Fe:InP(111)B substrate using the previously optimized growth conditions. The crystalline quality is improved significantly with the mosaicity twist reduced from 5.4\(^{\circ}\) to 1.0\(^{\circ}\). Furthermore, a layer without protective capping layer was grown on Si and studied after providing sufficient time for degradation. The uncapped layer on Si shows perfect quantization, while the layer on InP deviates by about 5\%. This may be caused by the higher crystalline quality, but variations in e.g. Sb content cannot be ruled out as the cause. Overall, the quantum anomalous Hall effect seems robust against changes in substrate and capping layer with only little deviations. Furthermore, the dependence of the quantum anomalous Hall effect on the thickness of the layers is investigated. Between 5-8 nm thickness the material typically transitions from a 2D topological insulator with hybridized top and bottom surface states to a 3D topological insulator. A set of samples with 6 nm, 8 nm, and 9 nm thickness exhibits the quantum anomalous Hall effect, while 5 nm and 15 nm thick layers show significant bulk contributions. The analysis of the longitudinal and Hall conductivity during the reversal of magnetization reveals distinct differences between different thicknesses. The 6 nm thick layer shows scaling consistent with the integer quantum Hall effect, while the 9 nm thick layer shows scaling expected for the topological surface states of a 3D topological insulator. The unique scaling of the 9 nm thick layer is of particular interest as it may be a result of axion electrodynamics in a 3D topological insulator. Subsequently, the influence of V doping on the structural and magnetic properties of the host material is studied systematically. Similarly to Bi alloying, increased V doping seems to flatten the layer surface significantly. With increasing V content, Te bonding partners are observed to increase simultaneously in a 2:3 ratio as expected for V incorporation on group-V sites. The linear contraction of the in-plane and out-of-plane lattice constants with increasing V doping is quantitatively consistent with the incorporation of V\(^{3+}\) ions, possibly mixed with V\(^{4+}\) ions, at the group-V sites. This is consistent with SQUID measurements showing a magnetization of 1.3 \(\mu_B\) per V ion. Finally, magnetically doped topological insulator heterostructures are fabricated and studied in magneto-transport. Trilayer heterostructures with a non-magnetic (Bi,Sb)\(_2\)Te\(_3\) layer sandwiched between two magnetically doped layers are predicted to host the axion insulator state if the two magnetic layers are decoupled and in antiparallel configuration. Magneto-transport measurements of such a trilayer heterostructure with 7 nm undoped (Bi,Sb)\(_2\)Te\(_3\) between 2 nm thick layers doped with 1.5 at.\% V exhibit a zero Hall plateau representing an insulating state. Similar results in the literature were interpreted as axion insulator state, but in the absence of a measurement showing the antiparallel magnetic orientation other explanations for the insulating state cannot be ruled out. Furthermore, heterostructures including a 2 nm thin, highly V doped layer region show an anomalous Hall effect of opposite sign compared to previous samples. A dependency on the thickness and position of the doped layer region is observed, which indicates that scattering at the interfaces causes contributions to the anomalous Hall effect of opposite sign compared to bulk scattering effects. Many interesting phenomena in quantum anomalous Hall insulators as well as axion insulators are still not unambiguously observed. This includes Majorana bound states in quantum anomalous Hall insulator/superconductor hybrid systems and the topological magneto-electric effect in axion insulators. The limited observation temperature of the quantum anomalous Hall effect of below 1 K could be increased in 3D topological insulator/magnetic insulator heterostructures which utilize the magnetic proximity effect. The main achievement of this thesis is the reproducible growth and characterization of (V,Bi,Sb)2Te3 layers exhibiting the quantum anomalous Hall effect. The detailed study of the structural requirements of the quantum anomalous Hall effect and the observation of the unique axionic scaling behavior in 3D magnetic topological insulator layers leads to a better understanding of the nature of this new quantum state. The high-precision measurements of the quantum anomalous Hall effect reporting the smallest deviation from the von Klitzing constant are an important step towards the realization of a zero-field quantum resistance standard.},
  subject      = {Bismutverbindungen},
  language  = {en}
}
@phdthesis{Winkler2020,
  author    = {Winkler, Erwin},
  title     = {Essays on International Trade and Labor Market Outcomes},
  doi       = {10.25972/OPUS-20983},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-209832},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {This thesis contributes to the understanding of the labor market effects of international trade, with a focus on the effects on wage and earnings inequality. The thesis draws on high-quality micro data and applies modern econometric techniques and theoretical concepts to improve our understanding of the distributional effects of international trade. The thesis focuses on the effects in Germany and the USA.},
  subject      = {Arbeitsmarkt},
  language  = {en}
}
@article{WinkelbeinerWandtEbertetal.2020,
  author    = {Winkelbeiner, Nicola and Wandt, Viktoria K. and Ebert, Franziska and Lossow, Kristina and Bankoglu, Ezgi E. and Martin, Maximilian and Mangerich, Aswin and Stopper, Helga and Bornhorst, Julia and Kipp, Anna P. and Schwerdtle, Tanja},
  title     = {A multi-endpoint approach to base excision repair incision activity augmented by PARylation and DNA damage levels in mice: impact of sex and age},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {18},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21186600},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285706},
  year      = {2020},
  abstract  = {Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2'-deoxyguanosine (8-oxodG), 5-hydroxy-2'-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.},
  language  = {en}
}
@phdthesis{Wind2020,
  author    = {Wind, Teresa Elisabeth},
  title     = {Einfluss von Alter und Polyneuropathie auf zeitliche Wahrnehmungsschwellen somatosensorischer und kin{\"a}sthetischer Stimuli und propriozeptive Leistungsf{\"a}higkeit},
  doi       = {10.25972/OPUS-20804},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208047},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Zeitliche Diskrimination somatosensorischer und kin{\"a}sthetischer Stimuli wurde als neurophysiologisches Korrelat f{\"u}r propriozeptive Pr{\"a}zision postuliert und bei verschiedenen Bewegungsst{\"o}rungen als pathologisch beschrieben. Ziel der Untersuchung war es, den Einfluss von Alter und Polyneuropathie auf die kin{\"a}sthetische (TDMT) und taktile (STDT) zeitliche Wahrnehmungsschwelle sowie die propriozeptive Genauigkeit bei Zeigeversuchen systematisch zu untersuchen. Hierf{\"u}r wurden 54 gesunde Probanden und 25 Polyneuropathie-Patienten im Alter zwischen 30 und 76 Jahren untersucht. Die STDT-Messung erfolgte mit Oberfl{\"a}chenelektroden, die an der Zeigefingerspitze bzw. am Großzehengrundgelenk angebracht wurden. Die TDMT-Werte wurden mit Hilfe einer sterilen Nadelelektrode erfasst, welche in den Musculus flexor carpi radialis bzw. Musculus tibialis anterior inseriert wurde. Die Daten zur Propriozeption wurden mit Hilfe eines Goniometers erhoben und beinhalteten dabei aktive Zeigeaufgaben (Zeigen auf eine LED, Nachahmung einer Bewegung anhand einer auf einem Computerbildschirm dargebotenen PFEIL-Darstellung unterschiedlicher L{\"a}nge) und die Einsch{\"a}tzung der Position der jeweiligen Extremit{\"a}t nach passiver Bewegung (PASSIV). Die Messungen erfolgten jeweils ohne visuelle R{\"u}ckmeldung. Die Zeigefehler (Abweichung von der Zielposition) bzw. Sch{\"a}tzfehler (Abweichung der gesch{\"a}tzten von der tats{\"a}chlichen Position nach passiver Auslenkung) wurden als Maß der propriozeptiven Pr{\"a}zision verwendet. Die Ergebnisse der gesunden Probandengruppe zeigten, dass h{\"o}heres Alter mit h{\"o}heren STDT- und TDMT-Werten korrelierte. Die Polyneuropathie-Patienten erzielten in allen Bereichen (Diskriminationsschwellen und Propriozeptionsaufgaben) signifikant schlechtere Ergebnisse als die gesunde Kontrollgruppe. Zus{\"a}tzlich konnte eine statistisch signifikante positive Korrelation zwischen der propriozeptiven Pr{\"a}zision bei den aktiven Zeige-Aufgaben (LED und PFEIL) und den zeitlichen Diskriminationsschwellen (STDT und TDMT) gezeigt werden. In Anbetracht dieser Ergebnisse sollten das Patienten-Alter und m{\"o}gliche St{\"o}rungen der peripheren Nervenleitung ber{\"u}cksichtigt werden, wenn STDT-und TDMT-Bestimmungen bei Patienten mit Bewegungsst{\"o}rungen angewendet werden. Die Korrelation zwischen den Diskriminationsschwellen und der Performance bei aktiven Zeigeversuchen (PFEIL- und LED-Aufgabe) legt nahe, dass STDT und TDMT Indikatoren der propriozeptiven Funktion sein k{\"o}nnten. Es ist weitere Forschungsarbeit notwendig, um diese Beziehung exakt zu beleuchten. Im Falle einer Best{\"a}tigung der Befunde auch bei Patienten mit Bewegungsst{\"o}rungen erscheint denkbar, dass sich STDT und TDMT als vergleichsweise leicht messbare und gut quantifizierbare Parameter der Propriozeption herausstellen mit Potenzial zur differenzialdiagnostischen Anwendung, m{\"o}glicherweise aber auch als Surrogatparameter einer gezielten rehabilitativen Behandlung.},
  subject      = {Propriozeption},
  language  = {de}
}
@phdthesis{Wiest2020,
  author    = {Wiest, Felix},
  title     = {Untersuchung der Nasenschleimhaut auf Genotoxizit{\"a}t und Entz{\"u}ndungsreaktionen nach Exposition mit Propylenglykol},
  doi       = {10.25972/OPUS-21513},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215138},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die E-Zigarette gewinnt in den letzten Jahren immer mehr an Popularit{\"a}t. Die Frage der Toxizit{\"a}t ist jedoch noch nicht abschließend gekl{\"a}rt, und es besteht weltweite Unsicherheit bei der Verwendung der E-Zigarette. Die vorliegende Arbeit untersucht menschliche Nasenschleimhautzellen nach Dampfexposition mit Propylenglykol, einem Hauptbestandteil der Liquide, auf m{\"o}gliche akute Entz{\"u}ndungsreaktionen, zytotoxische und genotoxische Wirkungen. Die Nasenschleimhautzellen von 10 Probanden wurden im Air-Liquid-Interface kultiviert und anschließend verschiedenen Konzentrationen von Propylenglykol ausgesetzt. Die Analyse erfolgte unter Verwendung eines Trypanblau-Tests, eines Comet-Assays, eines Mikrokern-Tests und eines IL-6- und IL-8-Sandwich-ELISAs. Der Trypanblau-Test zeigte keine Reduktion der Vitalit{\"a}t. Im Sandwich-ELISA konnte kein Anstieg der IL-6- und IL-8-Konzentrationen festgestellt werden. Im Comet-Assay zeigte das Olive Tail Moment in allen untersuchten Konzentrationen eine Sch{\"a}digung im Vergleich zur Negativkontrolle. Es zeigte sich auch eine dosisabh{\"a}ngige Sch{\"a}digung. Ein Unterschied zwischen der Reinsubstanz und der Negativkontrolle konnte im Mikrokern-Test festgestellt werden. Es wurden reparierbare Sch{\"a}den im Comet-Assay gefunden. Im Mikrokern-Test konnten diese nur in der Reinsubstanzkonzentration best{\"a}tigt werden. Die E-Zigarette sollte restriktiv verwendet werden, bis Langzeitstudien vorliegen. Dar{\"u}ber hinaus sollten die Hersteller die Inhaltsstoffe der Fl{\"u}ssigkeiten eindeutig angeben.},
  subject      = {Propylenglykol},
  language  = {de}
}
@phdthesis{Wiesner2020,
  author    = {Wiesner, Miriam},
  title     = {Stem Cell-based Adipose Tissue Engineering - Engineering of Prevascularized Adipose Tissue Constructs In Vitro \& Investigation on Gap Junctional Intercellular Communication in Adipose-derived Stem Cells},
  doi       = {10.25972/OPUS-18500},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-185005},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {In reconstructive and plastic surgery, there exists a growing demand of adequate tissue implants, since currently available strategies for autologous transplantation are limited by complications including transplant failure and donor site morbidity. By developing in vitro and in vivo autologous substitutes for defective tissue sites, adipose tissue engineering can address these challenges, although there are several obstacles to overcome. One of the major limitations is the sufficient vascularization of in vitro engineered large constructs that remains crucial and demanding for functional tissues. Decellularized jejunal segments may represent a suitable scaffolding system with preexisting capillary structures that can be repopulated with human microvascular endothelial cells (hMVECs), and a luminal matrix applicable for the adipogenic differentiation of human adipose-derived stem cells (hASCs). Hence, co-culture of these cells in jejunal segments, utilizing a custom-made bioreactor system, was characterized in terms of vascularization and adipose tissue development. Substantial adipogenesis of hASCs was demonstrated within the jejunal lumen in contrast to non-induced controls, and the increase of key adipogenic markers was verified over time upon induction. The development of major extracellular matrix components of mature adipose tissue, such as laminin and collagen IV, was shown within the scaffold in induced samples. Successful reseeding of the vascular network with hMVECs was demonstrated in long-term culture and co-localization of vascular structures and adipogenically differentiated hASCs was observed. Therefore, these results represent a novel approach for in vitro engineering of vascularized adipose tissue constructs that warrants further investigations in preclinical studies. Another still existing obstacle in adipose tissue engineering is the insufficient knowledge about the applied cells, for instance the understanding of how cells can be optimally expanded and differentiated for successful engineering of tissue transplants. Even though hASCs can be easily isolated from liposuction of abdominal fat depots, yielding low donor site morbidity, huge numbers of cells are required to entirely seed complex and large 3D matrices or scaffolds. Thus, cells need to be large-scale expanded in vitro on the premise of not losing their differentiation capacity caused by replicative aging. Accordingly, an improved differentiation of hASCs in adipose tissue engineering approaches remains still desirable since most engineered constructs exhibit an inhomogeneous differentiation pattern. For mesenchymal stem cells (MSCs), it has been shown that growth factor application can lead to a significant improvement of both proliferation and differentiation capacity. Especially basic fibroblast growth factor (bFGF) represents a potent mitogen for MSCs, while maintaining or even promoting their osteogenic, chondrogenic and adipogenic differentiation potential. As there are currently different contradictory information present in literature about the applied bFGF concentration and the explicit effect of bFGF on ASC differentiation, here, the effect of bFGF on hASC proliferation and differentiation capacity was investigated at different concentrations and time points in 2D culture. Preculture of hASCs with bFGF prior to adipogenic induction showed a remarkable effect, whereas administration of bFGF during culture did not improve adipogenic differentiation capacity. Furthermore, the observations indicated as mode of action an impact of this preculture on cell proliferation capacity, resulting in increased cellular density at the time of adipogenic induction. The difference in cell density at this time point appeared to be pivotal for increased adipogenic capacity of the cells, which was confirmed in a further experiment employing different seeding densities. Interestingly, furthermore, the obtained results suggested a cell-cell contact-mediated mechanism positively influencing adipogenic differentiation. As a consequence, subsequently, studies were conducted focusing on intercellular communication of these cells, which has hardly been investigated to date. Despite the multitude of literature on the differentiation capacity of ASCs, little is reported about the physiological properties contributing to and controlling the process of lineage differentiation. Direct intercellular communication between adjacent cells via gap junctions has been shown to modulate differentiation processes in other cell types, with connexin 43 (Cx43) being the most abundant isoform of the gap junction-forming connexins. Thus, in the present study we focused on the expression of Cx43 and gap junctional intercellular communication (GJIC) in hASCs, and its significance for adipogenic differentiation of these cells. Cx43 expression in hASCs was demonstrated histologically and on the gene and protein expression level and was shown to be greatly positively influenced by cell seeding density. Functionality of gap junctions was proven by dye transfer analysis in growth medium. Adipogenic differentiation of hASCs was shown to be also distinctly elevated at higher cell seeding densities. Inhibition of GJIC by 18α-glycyrrhetinic acid significantly compromised adipogenic differentiation, as demonstrated by histology, triglyceride quantification, and adipogenic marker gene expression. Flow cytometry analysis showed a lower proportion of cells undergoing adipogenesis when GJIC was inhibited, further indicating the importance of GJIC in the differentiation process. Altogether, these results demonstrate the impact of direct cell-cell communication via gap junctions on the adipogenic differentiation process of hASCs and may contribute to further integrate direct intercellular crosstalk in rationales for tissue engineering approaches.},
  subject      = {Tissue Engineering},
  language  = {en}
}
@phdthesis{Wieser2020,
  author    = {Wieser, Julia},
  title     = {Ver{\"a}nderungen des oralen Mikrobioms bei herausnehmbaren und festsitzenden kieferorthop{\"a}dischen Ger{\"a}ten},
  doi       = {10.25972/OPUS-21418},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214180},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die Studie befasste sich mit den Ver{\"a}nderungen des oralen Mikrobioms bei Patienten, die mit einer herausnehmbaren oder festsitzenden kieferorthop{\"a}dischen Apparatur behandelt wurden. W{\"a}hrend des sechsmonatigen Studienzeitraums wurden 25 Probanden hinsichtlich Streptococcus mutans und Lactobacillus mit dem CRT bacteria Test der Firma Ivoclar Vivadent untersucht. Abgesehen davon wurde ihre gingivale Gesundheit mittels Approximalraum-Plaque Index nach Saxer und M{\"u}hlemann und Papillenblutungsindex nach Lange et. al. ermittelt.},
  subject      = {Streptococcus mutans},
  language  = {de}
}
@phdthesis{Wiedemann2020,
  author    = {Wiedemann, Katharina},
  title     = {Fr{\"u}hzeitige Informationen {\"u}ber Systemgrenzen beim hochautomatisierten Fahren},
  doi       = {10.25972/OPUS-21658},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216581},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Fahrzeughersteller haben die Verf{\"u}gbarkeit sogenannter hochautomatisierter Fahrfunktionen (SAE Level 3; SAE, 2018) in ihren Modellen angek{\"u}ndigt. Hierdurch wird der Fahrer in der Lage sein, sich permanent von der Fahraufgabe abzuwenden und fahrfremden T{\"a}tigkeiten nachzugehen. Allerdings muss er immer noch als R{\"u}ckfallebene zur Verf{\"u}gung stehen, um im Fall von Systemgrenzen oder -fehlern (siehe Gold, Naujoks, Radlmayr, Bellem \& Jarosch, 2017), die Fahrzeugkontrolle zu {\"u}bernehmen. Das {\"U}bernahmeerfordernis wird dem Fahrer durch die Ausgabe einer {\"U}bernameaufforderung vermittelt. Die {\"U}bernahme der manuellen Fahrzeugf{\"u}hrung aus dem hochautomatisierten Fahren stellt aus psychologischer Sicht einen Aufgabenwechsel dar. Bei der Untersuchung von Aufgabenwechseln im Bereich der kognitiven und angewandten Psychologie zeigte sich vielfach, dass Aufgabenwechsel mit verl{\"a}ngerten Reaktionszeiten und erh{\"o}hten Fehlerraten assoziiert sind. F{\"u}r den Anwendungsfall des automatisierten Fahrens liegen ebenfalls eine Reihe empirischer Studien vor, die darauf hinweisen, dass der Wechsel zum manuellen Fahren mit einer Verschlechterung der Fahrleistung gegen{\"u}ber dem manuellen Fahren verbunden ist. Da Erkenntnisse vorliegen, dass eine Vorbereitung auf den Aufgabenwechsel die zu erwartenden Kosten verringern kann, ist das Ziel dieser Arbeit die Konzeption und empirische Evaluation einer Mensch-Maschine-Schnittstelle, die Nutzer hochautomatisierter Fahrzeuge durch fr{\"u}hzeitige Vorinformationen {\"u}ber Systemgrenzen auf die Kontroll{\"u}bernahme vorbereitet. Drei Experimente im Fahrsimulator mit Bewegungssystem betrachteten jeweils unterschiedliche Aspekte fr{\"u}hzeitiger Vorinformationen {\"u}ber bevorstehende {\"U}bernahmen. Das erste Experiment untersuchte, ob Fahrer {\"u}berhaupt von fr{\"u}hzeitigen Situationsank{\"u}ndigungen, beispielsweise im Sinne einer verbesserten {\"U}bernahmeleistung, profitieren. Das zweite Experiment befasste sich mit der Frage, wie solche Ank{\"u}ndigungen zeitlich und inhaltlich zu gestalten sind (d. h. wann sie pr{\"a}sentiert werden und welche Informationen sie enthalten sollten), und welchen Einfluss deren Gestaltung auf die Aufgabenbearbeitung (insbesondere deren Unterbrechung und sp{\"a}tere Wiederaufnahme) w{\"a}hrend der automatisierten Fahrt hat. Um herauszufinden, wie ein Anzeigekonzept zur l{\"a}ngerfristigen Planung von fahrfremden T{\"a}tigkeiten w{\"a}hrend des automatisierten Fahrens beitragen k{\"o}nnte, fand im dritten Experiment ein Vergleich von Situationsank{\"u}ndigungen, die vor dem Erreichen einer {\"U}bernahmesituation ausgegeben wurden, mit kontinuierlich pr{\"a}sentierten Informationen {\"u}ber die verbleibende Distanz zur n{\"a}chsten Systemgrenze statt. In allen Studien wurde neben den Auswirkungen fr{\"u}hzeitiger Vorinformationen auf die {\"U}bernahmeleistung und Bearbeitung von fahrfremden T{\"a}tigkeiten auch untersucht, welche Auswirkungen ein erweitertes {\"U}bernahmekonzept auf die Fahrerreaktion in Grenz- und Fehlerf{\"a}llen, in denen Vorinformationen entweder nicht oder fehlerhaft angezeigt wurden, hat. F{\"u}r die Gestaltung zuk{\"u}nftiger {\"U}bernahmekonzepte f{\"u}r hochautomatisierte Fahrzeuge kann basierend auf den Ergebnissen empfohlen werden, fr{\"u}hzeitige Anzeigen von Systemgrenzen zur Erm{\"o}glichung eines sicheren und komfortablen Wechsels zwischen dem manuellen und dem automatisierten Fahren in die Mensch-Maschine-Schnittstelle zu integrieren. Basierend auf den Ergebnissen dieser Arbeit liegt der empfohlene Zeitpunkt f{\"u}r diskrete Ank{\"u}ndigungen bei einer Reisegeschwindigkeit von 120 km/h bei etwa 1000 Meter (d. h. ca. 30 Sekunden) vor der Ausgabe der {\"U}bernahmeaufforderung. Zudem wird empfohlen zur Absch{\"a}tzung der verbleibenden Zeit im automatisierten Modus eine Anzeige der Entfernung zur n{\"a}chsten Systemgrenze in das Konzept zu integrieren, die dem Fahrer eine l{\"a}ngerfristige Aufgabenplanung erm{\"o}glicht. Neben der reinen Anzeige des {\"U}bernahmeerfordernisses sollten dem Fahrer auch Informationen {\"u}ber das erforderliche Fahrman{\"o}ver nach der Kontroll{\"u}bernahme {\"u}bermittelt werden.},
  subject      = {Autonomes Fahrzeug},
  language  = {de}
}
@phdthesis{Wick2020,
  author    = {Wick, Christoph},
  title     = {Optical Medieval Music Recognition},
  doi       = {10.25972/OPUS-21434},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214348},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {In recent years, great progress has been made in the area of Artificial Intelligence (AI) due to the possibilities of Deep Learning which steadily yielded new state-of-the-art results especially in many image recognition tasks. Currently, in some areas, human performance is achieved or already exceeded. This great development already had an impact on the area of Optical Music Recognition (OMR) as several novel methods relying on Deep Learning succeeded in specific tasks. Musicologists are interested in large-scale musical analysis and in publishing digital transcriptions in a collection enabling to develop tools for searching and data retrieving. The application of OMR promises to simplify and thus speed-up the transcription process by either providing fully-automatic or semi-automatic approaches. This thesis focuses on the automatic transcription of Medieval music with a focus on square notation which poses a challenging task due to complex layouts, highly varying handwritten notations, and degradation. However, since handwritten music notations are quite complex to read, even for an experienced musicologist, it is to be expected that even with new techniques of OMR manual corrections are required to obtain the transcriptions. This thesis presents several new approaches and open source software solutions for layout analysis and Automatic Text Recognition (ATR) for early documents and for OMR of Medieval manuscripts providing state-of-the-art technology. Fully Convolutional Networks (FCN) are applied for the segmentation of historical manuscripts and early printed books, to detect staff lines, and to recognize neume notations. The ATR engine Calamari is presented which allows for ATR of early prints and also the recognition of lyrics. Configurable CNN/LSTM-network architectures which are trained with the segmentation-free CTC-loss are applied to the sequential recognition of text but also monophonic music. Finally, a syllable-to-neume assignment algorithm is presented which represents the final step to obtain a complete transcription of the music. The evaluations show that the performances of any algorithm is highly depending on the material at hand and the number of training instances. The presented staff line detection correctly identifies staff lines and staves with an \$F_1\$-score of above \$99.5\\%\$. The symbol recognition yields a diplomatic Symbol Accuracy Rate (dSAR) of above \$90\\%\$ by counting the number of correct predictions in the symbols sequence normalized by its length. The ATR of lyrics achieved a Character Error Rate (CAR) (equivalently the number of correct predictions normalized by the sentence length) of above \$93\\%\$ trained on 771 lyric lines of Medieval manuscripts and of 99.89\\% when training on around 3.5 million lines of contemporary printed fonts. The assignment of syllables and their corresponding neumes reached \$F_1\$-scores of up to \$99.2\\%\$. A direct comparison to previously published performances is difficult due to different materials and metrics. However, estimations show that the reported values of this thesis exceed the state-of-the-art in the area of square notation. A further goal of this thesis is to enable musicologists without technical background to apply the developed algorithms in a complete workflow by providing a user-friendly and comfortable Graphical User Interface (GUI) encapsulating the technical details. For this purpose, this thesis presents the web-application OMMR4all. Its fully-functional workflow includes the proposed state-of-the-art machine-learning algorithms and optionally allows for a manual intervention at any stage to correct the output preventing error propagation. To simplify the manual (post-) correction, OMMR4all provides an overlay-editor that superimposes the annotations with a scan of the original manuscripts so that errors can easily be spotted. The workflow is designed to be iteratively improvable by training better models as soon as new Ground Truth (GT) is available.},
  subject      = {Neumenschrift},
  language  = {en}
}