@phdthesis{Bredemeyer2024,
  author    = {Bredemeyer, Cynthia Natascha},
  title     = {Akademisierung und Professionalisierung der Zahnheilkunde, insbesondere der Zahnchirurgie, in W{\"u}rzburg und Unterfranken im 19. Jahrhundert},
  doi       = {10.25972/OPUS-36387},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363878},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die Arbeit befasst sich mit der Akademisierung und Professionalisierung der Zahnheilkunde, insbesondere der Zahnchirurgie, in W{\"u}rzburg und Unterfranken im 19. Jahrhundert. Dies wurde insbesondere anhand des zahnchirurgischen Teils der Lehrchirurgischen Instrumentensammlung der Universit{\"a}t W{\"u}rzburg bzw. des Juliusspitals erforscht. Der zahnchirurgische Teil der Instrumentensammlung war bisher noch nicht erforscht worden und besteht aktuell aus 34+1 Instrumenten, die f{\"u}r diese Arbeit komplett katalogisiert wurden. F{\"u}r die Entwicklung der Instrumente im Verlauf des 19. Jahrhunderts wurde die Provenienz der Teilsammlung ergr{\"u}ndet und diese in den Kontext der Akademisierungsbewegung des 19. Jahrhunderts eingeordnet. Die Forschung wurde anhand der tats{\"a}chlich in der Praxis t{\"a}tigen und nach und nach akademisch ausgebildeten Personen nachvollzogen. Hierzu wurden neben den Instrumenten als Quelle die Adressb{\"u}cher der Stadt W{\"u}rzburg und die Matrikel-, Personal- und Vorlesungsverzeichnisse der Universit{\"a}t W{\"u}rzburg des gesamten 19. Jahrhunderts systematisch durchgearbeitet. Außerdem wurden Lehrb{\"u}cher aus dem nichtakademischen zahnchirurigischen Bereich (Bader) mit denen aus dem sich beginnenden akademischen Bereich analysiert. Anhand dieser Forschungsarbeit konnte dargelegt werden, dass die Zahnchirurgie sich analog zur Chiurgie aus dem handwerklichen Bereich abgekoppelt und nach und nach auf verschiedenen Stufen akademisiert hat. Die Zahnchirurgie hat sich "von unten nach oben" durch das Bestreben nichtakademisch ausgebildeter Menschen akademisiert.},
  subject      = {Zahnchirurgie},
  language  = {de}
}
@phdthesis{Heimberger2024,
  author    = {Heimberger, Kevin},
  title     = {Regulation pathways of c-MYC under glutamine-starving conditions in colon carcinoma cells},
  doi       = {10.25972/OPUS-36331},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363316},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Colon carcinomas (CRC) are statistically among the most fatal cancer types and hence one of the top reasons for premature mortality in the developed world. CRC cells are characterized by high proliferation rates caused by deregulation of gene transcription of proto-oncogenes and general chromosomal instability. On macroscopic level, CRC cells show a strongly altered nutrient and energy metabolism. This work presents research to understand general links between the metabolism and transcription alteration. Mainly focussing on glutamine dependency, shown in colon carcinoma cells and expression pathways of the pro-proliferation protein c-MYC. Previous studies showed that a depletion of glutamine in the cultivation medium of colon carcinoma cell lines caused a proliferation arrest and a strong decrease of overall c-MYC levels. Re-addition of glutamine quickly replenished c-MYC levels through an unknown mechanism. Several proteins altering this regulation mechanism were identified and proposed as possible starting point for further in detail studies to unveil the precise biochemical pathway controlling c-MYC translation repression and reactivation in a rapid manner. On a transcriptional level the formation of RNA:DNA hybrids, so called R-loops, was observed under glutamine depleted conditions. The introduction and overexpression of RNaseH1, a R-loop degrading enzyme, in combination with an ectopically expressed c-MYC variant, independent of cellular regulation mechanisms by deleting the regulatory 3'-UTR of the c-MYC gene, lead to a high rate of apoptotic cells in culture. Expression of a functionally inactive variant of RNaseH1 abolished this effect. This indicates a regulatory function of R-loops formed during glutamine starvation in the presence of c-MYC protein in a cell. Degradation of R-loops and high c-MYC levels in this stress condition had no imminent effect on the cell cycle progression is CRC cells but disturbed the nucleotide metabolism. Nucleotide triphosphates were strongly reduced in comparison to starving cells without R-loop degradation and proliferating cells. This study proposes a model of a terminal cycle of transcription termination, unregulated initiation and elongation of transcription leading to a depletion of energy resources of cells. This could finally lead to high apoptosis of the cells. Sequencing experiments to determine a coinciding of termination sites and R-loop formation sides failed so far but show a starting point for further studies in this essential survival mechanism involving R-loop formation and c-MYC downregulation.},
  subject      = {Myc},
  language  = {en}
}
@phdthesis{Beudert2024,
  author    = {Beudert, Matthias},
  title     = {Bioinspired Modification and Functionalization of Hydrogels for Applications in Biomedicine},
  doi       = {10.25972/OPUS-32288},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322887},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Over the years, hydrogels have been developed and used for a huge variety of different applications ranging from drug delivery devices to medical products. In this thesis, a poly(2-methyl-2-oxazoline) (POx) / poly(2-n-propyl-2-oxazine) (POzi) bioink was modified and analyzed for the use in biofabrication and targeted drug delivery. In addition, the protein fibrinogen (Fbg) was genetically modified for an increased stability towards plasmin degradation for its use as wound sealant. In Chapter 1, a thermogelling, printable POx/POzi-based hydrogel was modified with furan and maleimide moieties in the hydrophilic polymer backbone facilitating post-printing maturation of the constructs via Diels-Alder chemistry. The modification enabled long-term stability of the hydrogel scaffolds in aqueous solutions which is necessary for applications in biofabrication or tissue engineering. Furthermore, we incorporated RGD-peptides into the hydrogel which led to cell adhesion and elongated morphology of fibroblast cells seeded on top of the scaffolds. Additional printing experiments demonstrate that the presented POx/POzi system is a promising platform for the use as a bioink in biofabrication. Chapter 2 highlights the versatility of the POx/POzi hydrogels by adapting the system to a use in targeted drug delivery. We used a bioinspired approach for a bioorthogonal conjugation of insulin-like growth factor I (IGF-I) to the polymer using an omega-chain-end dibenzocyclooctyne (DBCO) modification and a matrix metalloprotease-sensitive peptide linker. This approach enabled a bioresponsive release of IGF-I from hydrogels as well as spatial control over the protein distribution in 3D printed constructs which makes the system a candidate for the use in personalized medicine. Chapter 3 gives a general overview over the necessity of wound sealants and the current generations of fibrin sealants on the market including advantages and challenges. Furthermore, it highlights trends and potential new strategies to tackle current problems and broadens the toolbox for future generations of fibrin sealants. Chapter 4 applies the concepts of recombinant protein expression and molecular engineering to a novel generation of fibrin sealants. In a proof-of-concept study, we developed a new recombinant fibrinogen (rFbg) expression protocol and a Fbg mutant that is less susceptible to plasmin degradation. Targeted lysine of plasmin cleavage sites in Fbg were exchanged with alanine or histidine in different parts of the molecule. The protein was recombinantly produced and restricted plasmin digest was analyzed using high resolution mass spectrometry. In addition to that, we developed a novel time resolved screening protocol for the detection of new potential plasmin cleavage sites for further amino acid exchanges in the fibrin sealant.},
  subject      = {Hydrogel},
  language  = {en}
}
@phdthesis{Endres2024,
  author    = {Endres, Erik},
  title     = {Kovalente Inhibitoren: Modellierung und Design},
  doi       = {10.25972/OPUS-35933},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359330},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Kovalente Inhibition stellt einen effektiven Weg dar, die Verweildauer des Liganden innerhalb einer Bindetasche zu erh{\"o}hen. In dieser Arbeit wurden theoretische Methoden angewendet, um die Reaktivit{\"a}t und den nichtkovalenten Zustand vor der Reaktion zu modellieren. Im Rahmen einer Fallstudie zu Cathepsin K wurden nichtkovalente Modelle von kovalenten Inhibitoren generiert. F{\"u}r verschiedene Komplexe aus Cathepsin K und einem kovalent gebundenem Liganden wurde der Zustand vor der Reaktion modelliert und dessen Stabilit{\"a}t im Rahmen einer klassischen MD-Simulation {\"u}berpr{\"u}ft. Die Stabilit{\"a}t des Warheads in der Bindetasche hing haupts{\"a}chlich vom gew{\"a}hlten Protonierungszustand der katalytischen Aminos{\"a}uren ab. F{\"u}r eine Reihe von Inhibitoren der ChlaDUB1 wurde ein Protokoll aus quantenmechanischen Rechnungen genutzt, um die Reaktivit{\"a}t verschiedener Warheads abzusch{\"a}tzen. Die erhaltenen Aktivierungsenergien korrelierten mit experimentell bestimmten Raten zur Inaktivierung des Enzyms. Im Rahmen eines Wirkstoffdesign-Projektes zur Deubiquitinase USP28 wurden von unpublizierten Kristallstrukturen ausgehend erste Docking-Experimente durchgef{\"u}hrt. Es konnte gezeigt werden, dass ein literaturbekannter Inhibitor von USP28 mit einem Warhead so modifiziert werden kann, dass die reaktive Einheit in direkter Nachbarschaft zu einem Cystein positioniert wird. F{\"u}r diese Warheads wurden ebenfalls quantenmechanische Rechnungen zur Bestimmung der Aktivierungsenergie durchgef{\"u}hrt. Um besser nachvollziehen zu k{\"o}nnen, warum bei einem Photoswitch-Inhibitor der Butyrylcholin-Esterase der cis-Zustand des Molek{\"u}ls besser inhibiert als der trans-Zustand, wurde eine Docking-Studie des Zustandes vor der Reaktion durchgef{\"u}hrt. Es konnte ein qualitatives Modell aufgestellt werden, das zeigt, dass der trans-Zustand aufgrund seiner l{\"a}ngeren Form mit wichtigen Aminos{\"a}uren am Eingang der Bindungstasche kollidiert.},
  subject      = {Molekulardynamik},
  language  = {de}
}
@phdthesis{Zhao2024,
  author    = {Zhao, Suting},
  title     = {Symmetry Resolution of Entanglement in Holography},
  doi       = {10.25972/OPUS-36385},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363854},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {This thesis investigates the charged moments and the symmetry-resolved entanglement entropy in the context of the AdS3/CFT2 duality. In the first part, I focus on the holographic U(1) Chern-Simons-Einstein gravity, a toy model of AdS3/CFT2 with U(1) Kac-Moody symmetry. I start with the vacuum background with a single entangling interval. I show that, apart from a partition function in the grand canonical ensemble, the charged moments can also be interpreted as the two-point function of vertex operators on the replica surface. For the holographic description, I propose a duality between the bulk U(1) Wilson line and the boundary vertex operators. I verify this duality by deriving the effective action for the Chern-Simons fields and comparing the result with the vertex correlator. In the twist field approach, I show that the charged moments are given by the correlation function of the charged twist operators and the additional background operators. To solve the correlation functions involved, I prove the factorization of the U(1) extended conformal block into a U(1) block and a Virasoro block. The general expression for the U(1) block is derived by directly summing over the current descendant states, and the result shows that it takes an identical form as the vertex correlators. This leads to the conclusion that the disjoint Wilson lines compute the neutral U(1) block. The final result for the symmetry-resolved entanglement entropy shows that it is always charge-independent in this model. In the second part, I study charged moments in higher spin holography, where the boundary theory is a CFT with W3 symmetry. I define the notion of the higher spin charged moments by introducing a spin-3 modular charge operator. Restricting to the vacuum background with a single entangling interval, I employ the grand canonical ensemble interpretation and calculate the charged moments via the known higher spin black hole solution. On the CFT side, I perform a perturbative expansion for the higher spin charged moments in terms of the connected correlation functions of the spin-3 modular charge operators. Using the recursion relation for the correlation functions of the W3 currents, I evaluate the charged moments up to the quartic order of the chemical potential. The final expression matches with the holographic result. My results both for U(1) Chern-Simons Einstein gravity and W3 higher spin gravity constitute novel checks of the AdS3/CFT2 correspondence.},
  subject      = {AdS-CFT-Korrespondenz},
  language  = {en}
}
@phdthesis{Dietrich2024,
  author    = {Dietrich, Oliver},
  title     = {Integrating single-cell multi-omics to decipher host-pathogen interactions},
  doi       = {10.25972/OPUS-36013},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360138},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Interactions between host and pathogen determine the development, progression and outcomes of disease. Medicine benefits from better descriptions of these interactions through increased precision of prevention, diagnosis and treatment of diseases. Single-cell genomics is a disruptive technology revolutionizing science by increasing the resolution with which we study diseases. Cell type specific changes in abundance or gene expression are now routinely investigated in diseases. Meanwhile, detecting cellular phenotypes across diseases can connect scientific fields and fuel discovery. Insights acquired through systematic analysis of high resolution data will soon be translated into clinical practice and improve decision making. Therefore, the continued use of single-cell technologies and their application towards clinical samples will improve molecular interpretation, patient stratification, and the prediction of outcomes. In the past years, I was fortunate to participate in interdisciplinary research groups bridging biology, clinical research and data science. I was able to contribute to diverse projects through computational analysis and biological interpretation of sequencing data. Together, we were able to discover cellular phenotypes that influence disease progression and outcomes as well as the response to treatment. Here, I will present four studies that I have conducted in my PhD. First, we performed a case study of relapse from cell-based immunotherapy in Multiple Myeloma. We identified genomic deletion of the epitope as mechanism of immune escape and implicate heterozygosity or monosomy of the genomic locus at baseline as a potential risk factor. Second, we investigated the pathomechanisms of severe COVID-19 at the earliest stage of the COVID- 19 pandemic in Germany in March 2020. We discovered that profibrotic macrophages and lung fibrosis can be caused by SARS-CoV-2 infection. Third, we used a mouse model of chronic infection with Staphylococcus aureus that causes Osteomyelitis similar to the human disease. We were able to identify dysregulated immunometabolism associated with the generation of myeloid-derived suppressor cells (MDSC). Fourth, we investigated Salmonella infection of the human small intestine in an in vitro model and describe features of pathogen invasion and host response. Overall, I have been able to successfully employ single-cell sequencing to discover important aspects of diseases ranging from development to treatment and outcome. I analyzed samples from the clinics, human donors, mouse models and organoid models to investigate different aspects of diseases and managed to integrate data across sample types, technologies and diseases. Based on successful studies, we increased our efforts to combine data from multiple sources to build comprehensive references for the integration of large collections of clinical samples. Our findings exemplify how single-cell sequencing can improve clinical research and highlights the potential of mechanistic discoveries to drive precision medicine.},
  subject      = {Einzelzellanalyse},
  language  = {en}
}
@phdthesis{Papay2024,
  author    = {Papay, Marion},
  title     = {Notwendigkeit der pr{\"a}operativen Reposition von distalen, nach dorsal dislozierten Radiusfrakturen bei bestehender Operationsindikation im Hinblick auf das Schmerzniveau sowie postoperative Ergebnisse},
  doi       = {10.25972/OPUS-36388},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363882},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die distale Radiusfraktur geh{\"o}rt zu den h{\"a}ufigsten Frakturen in Deutschland mit einem Inzidenzanstieg im Alter unter Betonung des weiblichen Geschlechts. Dabei zeigt sich ein zunehmender Trend in Richtung operative Versorgung, allen voran die Versorgung mittels winkelstabiler Plattensysteme. Instabile, distale Radiusfrakturen werden dabei vor geplanter operativer Versorgung im Rahmen der Initialbehandlung {\"u}blicherweise geschlossen reponiert und im Gipsverband retiniert. Ziel der vorliegenden monozentrischen, prospektiv randomisierten Studie mit zwei Studiengruppen war es herauszufinden, ob sich das Unterlassen der Reposition vor geplanter Operation nachteilig auf das Schmerzniveau in der pr{\"a}operativen Phase auswirkt und ob sich durch die Dislokation Nachteile in Bezug auf den Nervus medianus im Sinne eines Traktionsschadens sowie bez{\"u}glich des klinisch-radiologischen Ausheilungsergebnisses zeigen. Die Studie zeigte, dass das Schmerzempfinden w{\"a}hrend der pr{\"a}operativen Gipsbehandlung unabh{\"a}ngig von einer vorherigen Reposition war. F{\"u}r den prim{\"a}ren Endpunkt an Tag 1 nach der Akutbehandlung konnte statistisch signifikante Nichtunterlegenheit der Gruppe ohne Reposition gegen{\"u}ber der Gruppe mit Reposition nachgewiesen werden. Gleiches galt f{\"u}r Tag 2, sowohl f{\"u}r die absoluten Schmerzniveaus als auch f{\"u}r die Schmerzlinderung. Das Unterlassen der Reposition hatte zudem keine nachteiligen Effekte auf den Nervus medianus. Gleiches zeigte sich f{\"u}r das klinische und radiologische Ausheilungsergebnis. F{\"u}r die funktionellen DASH- und Krimmer-Scores konnte ein Jahr postoperativ ebenfalls statistisch signifikante Nichtunterlegenheit der Gruppe ohne Reposition nachgewiesen werden. Diese Erkenntnisse best{\"a}tigen die in der Literatur vorhandenen Ergebnisse verschiedener Studien dahingehend, dass das Unterlassen der Reposition keine nachteiligen Effekte auf das postoperative Outcome hat. Einige Studien verdeutlichen zudem, dass es nach Reposition, insbesondere bei Vorliegen gewisser Risiko- und Instabilit{\"a}tsfaktoren, ohnehin zur sekund{\"a}ren Dislokation kommt, sodass die generelle Notwendigkeit der Reposition vor Gipsanlage sowohl vor einer operativen als auch vor einer konservativen Weiterbehandlung angezweifelt werden muss.},
  subject      = {distale Radiusfraktur},
  language  = {de}
}
@phdthesis{Aroko2024,
  author    = {Aroko, Erick Onyango},
  title     = {Trans-regulation of \(Trypanosoma\) \(brucei\) variant surface glycoprotein (VSG) mRNA and structural analysis of a \(Trypanosoma\) \(vivax\) VSG using X-ray crystallography},
  doi       = {10.25972/OPUS-24177},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241773},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {African trypanosomes are unicellular parasites that cause nagana and sleeping sickness in livestock and man, respectively. The major pathogens for the animal disease include Trypanosoma vivax, T. congolense, and T. brucei brucei, whereas T. b. gambiense and T. b. rhodesiense are responsible for human infections. Given that the bloodstream form (BSF) of African trypanosomes is exclusively extracellular, its cell surface forms a critical boundary with the host environment. The cell surface of the BSF African trypanosomes is covered by a dense coat of immunogenic variant surface glycoproteins (VSGs). This surface protein acts as an impenetrable shield that protects the cells from host immune factors and is also involved in antibody clearance and antigenic variation, which collectively ensure that the parasite stays ahead of the host immune system. Gene expression in T. brucei is markedly different from other eukaryotes: most genes are transcribed as long polycistronic units, processed by trans-splicing a 39-nucleotide mini exon at the 5′ and polyadenylation at the 3′ ends of individual genes to generate the mature mRNA. Therefore, gene expression in T. brucei is regulated post-transcriptionally, mainly by the action of RNA binding proteins (RBPs) and conserved elements in the 3′ untranslated regions (UTR) of transcripts. The expression of VSGs is highly regulated, and only a single VSG gene is expressed at a time from one of the ~15 subtelomeric domains termed bloodstream expression sites (BES). When cells are engineered to simultaneously express two VSGs, the total VSG mRNA do not exceed the wild type amounts. This suggests that a robust VSG mRNA balancing mechanism exists in T. brucei. The present study uses inducible and constitutive expression of ectopic VSG genes to show that the endogenous VSG mRNA is regulated only if the second VSG is properly targeted to the ER. Additionally, the endogenous VSG mRNA response is triggered when high amounts of the GFP reporter with a VSG 3′UTR is targeted to the ER. Further evidence that non-VSG ER import signals can efficiently target VSGs to the ER is presented. This study suggests that a robust trans-regulation of the VSG mRNA is elicited at the ER through a feedback loop to keep the VSG transcripts in check and avoid overshooting the secretory pathway capacity. Further, it was shown that induction of expression of the T. vivax VSG ILDat1.2 in T. brucei causes a dual cell cycle arrest, with concomitant upregulation of the protein associated with differentiation (PAD1) expression. It could be shown that T. vivax VSG ILDat1.2 can only be sufficiently expressed in T. brucei after replacing its native GPI signal peptide with that of a T. brucei VSG. Taken together, these data indicate that inefficient VSG GPI anchoring and expression of low levels of the VSG protein can trigger differentiation from slender BSF to stumpy forms. However, a second T. vivax VSG, ILDat2.1, is not expressed in T. brucei even after similar modifications to its GPI signals. An X-ray crystallography approach was utilized to solve the N-terminal domain (NTD) structure of VSG ILDat1.2. This is first structure of a non-T. brucei VSG, and the first of a surface protein of T. vivax to be solved. VSG ILDat1.2 NTD maintains the three-helical bundle scaffold conserved in T. brucei surface proteins. However, it is likely that there are variations in the architecture of the membrane proximal region of the ILDat1.2 NTD and its CTD from T. brucei VSGs. The tractable T. brucei system is presented as a model that can be used to study surface proteins of related trypanosome species, thus creating avenues for further characterization of trypanosome surface coats.},
  subject      = {Trypanosoma vivax},
  language  = {en}
}
@phdthesis{Abelein2024,
  author    = {Abelein, Christian Karl},
  title     = {„Ich habe mich so daran gew{\"o}hnt, daß ich beinahe nie dichte ohne zugleich zu singen!" - Der Briefwechsel zwischen August Heinrich Hoffmann von Fallersleben (1798-1874) und Hans Michael Schletterer (1824-1893) als Dokument einer konstruktiven Zusammenarbeit zwischen Dichter und Komponist im 19. Jahrhundert.},
  doi       = {10.25972/OPUS-36386},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363862},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die von Friedhelm Brusniak und Ulrich Konrad betreute und angenommene Dissertation nimmt den Briefwechsel zwischen August Heinrich Hoffmann von Fallersleben und dem j{\"u}ngeren Augsburger Kapellmeister und Komponisten Hans Michael Schletterer in den Jahren 1862 bis 1873 in den Blick und dokumentiert dabei Hoffmanns Einfluss auf den Entstehungsprozess der Vertonungen seiner Lieder, besonders seiner Kinderlieder. Die Arbeit beleuchtet zudem den Erfahrungsschatz, den sich der ‚Dichter-S{\"a}nger' Hoffmann von Fallersleben auch durch die Zusammenarbeit mit anderen Musikern seiner Zeit, vorrangig Ludwig Christian Erk (1807-1883) und Ernst Heinrich Leopold Richter (1805-1876), erworben hatte. Dar{\"u}ber hinaus werden in der Korrespondenz Themen des gesellschaftlichen und politischen Lebens, der privaten und beruflichen Situation beider wie auch Hoffmanns Rolle als v{\"a}terlicher Berater Schletterers ber{\"u}hrt. Die Arbeit darf als neuer substantieller Beitrag der Hoffmann-Forschung und der interdisziplin{\"a}ren Liedforschung angesehen werden, der insbesondere der Kinderliedforschung neue Impulse verleiht.},
  subject      = {Hoffmann von Fallersleben, August Heinrich},
  language  = {de}
}
@phdthesis{Yu2024,
  author    = {Yu, Yanying},
  title     = {Applied machine learning for the analysis of CRISPR-Cas systems},
  doi       = {10.25972/OPUS-32021},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320219},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Among the defense strategies developed in microbes over millions of years, the innate adaptive CRISPR-Cas immune systems have spread across most of bacteria and archaea. The flexibility, simplicity, and specificity of CRISPR-Cas systems have laid the foundation for CRISPR-based genetic tools. Yet, the efficient administration of CRISPR-based tools demands rational designs to maximize the on-target efficiency and off-target specificity. Specifically, the selection of guide RNAs (gRNAs), which play a crucial role in the target recognition of CRISPR-Cas systems, is non-trivial. Despite the fact that the emerging machine learning techniques provide a solution to aid in gRNA design with prediction algorithms, design rules for many CRISPR-Cas systems are ill-defined, hindering their broader applications. CRISPR interference (CRISPRi), an alternative gene silencing technique using a catalytically dead Cas protein to interfere with transcription, is a leading technique in bacteria for functional interrogation, pathway manipulation, and genome-wide screens. Although the application is promising, it also is hindered by under-investigated design rules. Therefore, in this work, I develop a state-of-art predictive machine learning model for guide silencing efficiency in bacteria leveraging the advantages of feature engineering, data integration, interpretable AI, and automated machine learning. I first systematically investigate the influential factors that attribute to the extent of depletion in multiple CRISPRi genome-wide essentiality screens in Escherichia coli and demonstrate the surprising dominant contribution of gene-specific effects, such as gene expression level. These observations allowed me to segregate the confounding gene-specific effects using a mixed-effect random forest (MERF) model to provide a better estimate of guide efficiency, together with the improvement led by integrating multiple screens. The MERF model outperformed existing tools in an independent high-throughput saturating screen. I next interpret the predictive model to extract the design rules for robust gene silencing, such as the preference for cytosine and disfavoring for guanine and thymine within and around the protospacer adjacent motif (PAM) sequence. I further incorporated the MERF model in a web-based tool that is freely accessible at www.ciao.helmholtz-hiri.de. When comparing the MERF model with existing tools, the performance of the alternative gRNA design tool optimized for CRISPRi in eukaryotes when applied to bacteria was far from satisfying, questioning the robustness of prediction algorithms across organisms. In addition, the CRISPR-Cas systems exhibit diverse mechanisms albeit with some similarities. The captured predictive patterns from one dataset thereby are at risk of poor generalization when applied across organisms and CRISPR-Cas techniques. To fill the gap, the machine learning approach I present here for CRISPRi could serve as a blueprint for the effective development of prediction algorithms for specific organisms or CRISPR-Cas systems of interest. The explicit workflow includes three principle steps: 1) accommodating the feature set for the CRISPR-Cas system or technique; 2) optimizing a machine learning model using automated machine learning; 3) explaining the model using interpretable AI. To illustrate the applicability of the workflow and diversity of results when applied across different bacteria and CRISPR-Cas systems, I have applied this workflow to analyze three distinct CRISPR-Cas genome-wide screens. From the CRISPR base editor essentiality screen in E. coli, I have determined the PAM preference and sequence context in the editing window for efficient editing, such as A at the 2nd position of PAM, A/TT/TG downstream of PAM, and TC at the 4th to 5th position of gRNAs. From the CRISPR-Cas13a screen in E. coli, in addition to the strong correlation with the guide depletion, the target expression level is the strongest predictor in the model, supporting it as a main determinant of the activation of Cas13-induced immunity and better characterizing the CRISPR-Cas13 system. From the CRISPR-Cas12a screen in Klebsiella pneumoniae, I have extracted the design rules for robust antimicrobial activity across K. pneumoniae strains and provided a predictive algorithm for gRNA design, facilitating CRISPR-Cas12a as an alternative technique to tackle antibiotic resistance. Overall, this thesis presents an accurate prediction algorithm for CRISPRi guide efficiency in bacteria, providing insights into the determinants of efficient silencing and guide designs. The systematic exploration has led to a robust machine learning approach for effective model development in other bacteria and CRISPR-Cas systems. Applying the approach in the analysis of independent CRISPR-Cas screens not only sheds light on the design rules but also the mechanisms of the CRISPR-Cas systems. Together, I demonstrate that applied machine learning paves the way to a deeper understanding and a broader application of CRISPR-Cas systems.},
  subject      = {Maschinelles Lernen},
  language  = {en}
}
@phdthesis{KuklovskyformerFinke2024,
  author    = {Kuklovsky [former Finke], Valerie},
  title     = {Are some bees smarter than others? An examination of consistent individual differences in the cognitive abilities of honey bees},
  doi       = {10.25972/OPUS-32301},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323012},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Cognition refers to the ability to of animals to acquire, process, store and use vital information from the environment. Cognitive processes are necessary to predict the future and reduce the uncertainty of the ever-changing environment. Classically, research on animal cognition focuses on decisive cognitive tests to determine the capacity of a species by the testing the ability of a few individuals. This approach views variability between these tested key individuals as unwanted noise and is thus often neglected. However, inter-individual variability provides important insights to behavioral plasticity, cognitive specialization and brain modularity. Honey bees Apis mellifera are a robust and traditional model for the study of learning, memory and cognition due to their impressive capabilities and rich behavioral repertoire. In this thesis I have applied a novel view on the learning abilities of honey bees by looking explicitly at individual differences in a variety of learning tasks. Are some individual bees consistently smarter than some of her sisters? If so, will a smart individual always perform good independent of the time, the context and the cognitive requirements or do bees show distinct isolated 'cognitive modules'? My thesis presents the first comprehensive investigation of consistent individual differences in the cognitive abilities of honey bees. To speak of an individual as behaving consistently, a crucial step is to test the individual multiple times to examine the repeatability of a behavior. I show that free-flying bees remain consistent in a visual discrimination task for three consecutive days. Successively, I explored individual consistency in cognitive proficiency across tasks involving different sensory modalities, contexts and cognitive requirements. I found that free-flying bees show a cognitive specialization between visual and olfactory learning but remained consistent across a simple discrimination task and a complex concept learning task. I wished to further explore individual consistency with respect to tasks of different cognitive complexity, a question that has never been tackled before in an insect. I thus performed a series of four experiments using either visual or olfactory stimuli and a different training context (free-flying and restrained) and tested bees in a discrimination task, reversal learning and negative patterning. Intriguingly, across all these experiments I evidenced the same results: The bees' performances were consistent across the discrimination task and reversal learning and negative patterning respectively. No association was evidenced between reversal learning and negative patterning. After establishing the existence of consistent individual differences in the cognitive proficiency of honey bees I wished to determine factors which could underlie these differences. Since genetic components are known to underlie inter-individual variability in learning abilities, I studied the effects of genetics on consistency in cognitive proficiency by contrasting bees originating from either from a hive with a single patriline (low genetic diversity) or with multiple patrilines (high genetic diversity). These two groups of bees showed differences in the patterns of individually correlated performances, indicating a genetic component accounts for consistent cognitive individuality. Another major factor underlying variability in learning performances is the individual responsiveness to sucrose solution and to visual stimuli, as evidenced by many studies on restrained bees showing a positive correlation between responsiveness to task relevant stimuli and learning performances. I thus tested whether these relationships between sucrose/visual responsiveness and learning performances are applicable for free-flying bees. Free-flying bees were again subjected to reversal learning and negative patterning and subsequently tested in the laboratory for their responsiveness to sucrose and to light. There was no evidence of a positive relationship between sucrose/visual responsiveness and neither performances of free-flying bees in an elemental discrimination, reversal learning and negative patterning. These findings indicate that relationships established between responsiveness to task relevant stimuli and learning proficiency established in the laboratory with restrained bees might not hold true for a completely different behavioral context i.e. for free-flying bees in their natural environment. These results show that the honey bee is an excellent insect model to study consistency in cognitive proficiency and to identify the underlying factors. I mainly discuss the results with respect to the question of brain modularity in insects and the adaptive significance of individuality in cognitive abilities for honey bee colonies. I also provide a proposition of research questions which tie in this theme of consistent cognitive proficiency and could provide fruitful areas for future research.},
  subject      = {Lernen},
  language  = {en}
}
@phdthesis{Dalkmann2024,
  author    = {Dalkmann, Theresa},
  title     = {Evaluierung prognostischer und pr{\"a}diktiver Biomarker beim neoadjuvant vorbehandelten Rektumkarzinom},
  doi       = {10.25972/OPUS-36336},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363368},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Fragestellung. Osteopontin (OPN) kann im Blut nachgewiesen werden und wird bei vielen Tumorentit{\"a}ten exprimiert, wie auch der Tyrosinkinaserezeptor c-Met und sein Ligand, das Zytokin Hepatocyte Growth Factor (HGF). In der vorliegenden Arbeit untersuchten wir die prognostische und pr{\"a}diktive Wertigkeit der Plasmakonzentrationen von OPN, c-Met und HGF bei Patienten mit lokal fortgeschrittenem Rektumkarzinom (LARC). Methodik. Das Plasma von 63 Patienten mit LARC wurde untersucht. Die Blutentnahmen (EDTA-Plasma) erfolgten vor Therapiebeginn sowie im Verlauf. Die Plasmaspiegel von OPN, c-Met und HGF wurden mittels Enzyme-Linked Immunosorbent Assay analysiert. Die Konzentrationen wurden auf eine Korrelation mit den klinischen Parametern untersucht. Ergebnisse. 68 Patienten wurden neoadjuvant mit einer Radiochemotherapie behandelt, 63 Blutproben wurden untersucht. Initial befanden sich nach UICC 14 Patienten in Stadium II, 47 in Stadium III und 7 in Stadium IV. Das mediane Follow-Up betrug 29,87 Monate. 20 der 68 Patienten (29,4 \%) verstarben, 19 entwickelten Fernmetastasen. OPN korrelierte signifikant mit dem {\"U}berleben (p=0,001). OPN-Werte korrelierten mit dem pT-Stadium (R:0,445 p=0,018) und dem pUICC-Stadium (R:0,412 p=0,018), sowie mit dem Auftreten von Fernmetastasen (R:0,271 p=0,031). Eine Korrelation zwischen OPN und dem Therapieansprechen konnte gezeigt werden: pathologisch komplette Remission (pCR) (R:0,379 p=0,001), NAR-Score (R:0,373 p=0,015), TRG (R:0,380 p=0,020). Die logistische Regressionsanalyse ergab eine Pr{\"a}diktivit{\"a}t OPNs f{\"u}r pCR (OR:0,990 p=0,009), NAR-Score (OR:1,008 p=0,007), TRG (OR:0,459 p=0,008). C-Met und HGF korrelierten nicht mit dem {\"U}berleben. F{\"u}r c-Met und HGF ergab sich keine Korrelation zu initialen klinischen Daten und Therapieansprechen. Die logistische Regression ergab keinen pr{\"a}diktiven Wert. Schlussfolgerung. Die Plasmakonzentration von OPN besitzt prognostische und pr{\"a}diktive Wertigkeit beim LARC. Die Konzentrationen von c-Met und HGF sind nicht prognostisch f{\"u}r das {\"U}berleben oder pr{\"a}diktiv f{\"u}r das Therapieansprechen.},
  subject      = {Biomarker},
  language  = {de}
}
@phdthesis{Djakowski2024,
  author    = {Djakowski, Paul},
  title     = {Schulische politische Bildung in Deutschland und Polen. Eine kompetenzbasierte komparative Analyse der Leitf{\"a}cher f{\"u}r politische Bildung anhand von Stundentafeln und Curricula allgemeinbildender staatlicher Schulformen der Primarstufe sowie der Sekundarstufen I und II im Schuljahr 2019/20},
  publisher = {W{\"u}rzburg University Press},
  address   = {W{\"u}rzburg},
  isbn      = {978-3-95826-230-0},
  doi       = {10.25972/WUP-978-3-95826-231-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326799},
  school      = {W{\"u}rzburg University Press},
  pages     = {XXI, 593},
  year      = {2024},
  abstract  = {Politische Bildung {\"u}bt nicht nur einen großen Einfluss auf die zuk{\"u}nftige Konstellation des politischen Systems aus, sondern beeinflusst ebenfalls das soziale Miteinander pr{\"a}gend. Damit werden entscheidende Weichen f{\"u}r die Entwicklung der Gesellschaft, der Nation und des Staates gestellt. Im Zuge dieses Prozesses durchl{\"a}uft jeder junge B{\"u}rger einen politischen Bildungsweg an Schulen. Die Vorgaben dar{\"u}ber, wie schulische politische Bildung auszusehen hat und welche Kompetenzen Sch{\"u}ler in diesem Zusammenhang erwerben sollen, geben die Kultus- bzw. Bildungsministerien in Curricula vor, verbindlich f{\"u}r alle Lehrer. Durch eine komparative Analyse der Curricula kann damit eindeutig die staatlich vorgegebene politische, gesellschaftliche und soziale Richtung festgestellt werden, die junge Menschen einschlagen sollen. Welche edukativen Ziele der politischen Bildung werden verfolgt? Was sollen Sch{\"u}ler lernen, um mit diesen Kompetenzen die Zukunft ihres Kollektivs zu gestalten? Wo liegen die Gemeinsamkeiten und Unterschiede zweier Staaten, in unserem Fall Deutschlands und Polens, im Hinblick auf die schulische politische Bildung? Beantwortet werden diese Fragestellungen durch das Anwenden zweier Methoden der qualitativen Sozialforschung, der komparativen Inhaltsanalyse, zum einen der strukturierenden zum anderen der induktiven. Davor erfolgt eine komparativ quantitative Untersuchung, die den Umfang der Unterrichtszeit in den Leitf{\"a}chern f{\"u}r politische Bildung in allen Bundesl{\"a}ndern und in Polen vergleicht, was einer empirischen Totalerhebung der komplex umfangreichen Daten entspricht. Die quantitativen Forschungsergebnisse zeigen deutliche Differenzen zwischen Deutschland und Polen, in einem der beiden Staaten wird signifikant mehr Zeit f{\"u}r politische Bildung im Leitfach dieser Disziplin investiert als im anderen. Anhand der qualitativen Daten ist zu erkennen, dass einerseits eine gemeinsame Grundbasis von Kompetenzen der politischen Bildung zwischen Deutschland und Polen besteht. Anderseits stechen in beiden L{\"a}ndern eindeutige Unterschiede hervor, deren Ursprung zum einen historische Erfahrungen der Nationen und Staaten abbildet, zum anderen aktuell gegens{\"a}tzliche politische Interessen untermauert.},
  subject      = {Politische Bildung},
  language  = {de}
}
@phdthesis{Hartmann2024,
  author    = {Hartmann, Oliver},
  title     = {Development of somatic modified mouse models of Non-Small cell lung cancer},
  doi       = {10.25972/OPUS-36340},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363401},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In 2020, cancer was the leading cause of death worldwide, accounting for nearly 10 million deaths. Lung cancer was the most common cancer, with 2.21 million cases per year in both sexes. This non-homogeneous disease is further subdivided into small cell lung cancer (SCLC, 15\%) and non-small cell lung cancer (NSCLC, 85\%). By 2023, the American Cancer Society estimates that NSCLC will account for 13\% of all new cancer cases and 21\% of all estimated cancer deaths. In recent years, the treatment of patients with NSCLC has improved with the development of new therapeutic interventions and the advent of targeted and personalised therapies. However, these advances have only marginally improved the five-year survival rate, which remains alarmingly low for patients with NSCLC. This observation highlights the importance of having more appropriate experimental and preclinical models to recapitulate, identify and test novel susceptibilities in NSCLC. In recent years, the Trp53fl/fl KRaslsl-G12D/wt mouse model developed by Tuveson, Jacks and Berns has been the main in vivo model used to study NSCLC. This model mimics ADC and SCC to a certain extent. However, it is limited in its ability to reflect the genetic complexity of NSCLC. In this work, we use CRISPR/Cas9 genome editing with targeted mutagenesis and gene deletions to recapitulate the conditional model. By comparing the Trp53fl/fl KRaslsl- G12D/wt with the CRISPR-mediated Trp53mut KRasG12D, we demonstrated that both showed no differences in histopathological features, morphology, and marker expression. Furthermore, next-generation sequencing revealed a very high similarity in their transcriptional profile. Adeno-associated virus-mediated tumour induction and the modular design of the viral vector allow us to introduce additional mutations in a timely manner. CRISPR-mediated mutation of commonly mutated tumour suppressors in NSCLC reliably recapitulated the phenotypes described in patients in the animal model. Lastly, the dual viral approach could induce the formation of lung tumours not only in constitutive Cas9 expressing animals, but also in wildtype animals. Thus, the implementation of CRISPR genome editing can rapidly advance the repertoire of in vivo models for NSCLC research. Furthermore, it can reduce the necessity of extensive breeding.},
  subject      = {CRISPR/Cas-Methode},
  language  = {en}
}
@phdthesis{Schwenkert2024,
  author    = {Schwenkert, Marc},
  title     = {Zwei Burschenschafter als B{\"u}rgermeister im Dritten Reich. Theo Memmel in W{\"u}rzburg und Paul May in Halle im Vergleich.},
  doi       = {10.25972/OPUS-36096},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360966},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In der Dissertation „Zwei Burschenschafter als B{\"u}rgermeister im Dritten Reich. Theo Memmel in W{\"u}rzburg und Paul May in Halle im Vergleich." steht die Untersuchung der Lebenswege der beiden Wahlbeamten Dr. Paul May und Theodor Memmel anhand ihrer Biographien im Fokus. May glitt dank seiner sich stetig erweiternden Fachkenntnisse sowie seiner Anpassungsf{\"a}higkeit durchweg in Leistungspositionen problemlos durch vier politische Systeme - vom Kaiserreich bis zur DDR. Seiner b{\"u}rgerlichen politischen Ausrichtung blieb er hierbei stets treu. Memmel hingegen machte bedingt durch seine an-dere und gravierendere Weltkriegserfahrung einen Prozess vom politisch des-interessierten Front- und Freikorpsk{\"a}mpfer {\"u}ber die Bayerische Volkspartei hin zum {\"u}berzeugten Nationalsozialisten. Nach dem Untergang des Dritten Reichs stand er vor dem Nichts, sowohl in beruflicher als auch in politischer Hinsicht. In seiner Studentenverbindung fand er jedoch einen Raum, in dem er sich engagieren und Anerkennung finden konnte. Da May und Memmel durch ihre gemeinsame studentische Korporation gleich sozialisiert wurden und sie sich auf unterschiedliche Weise wie ein ro-ter Faden durch ihr Leben zog, erfuhr diese ebenfalls eine Untersuchung. Hierbei ergab sich, dass die Wandlung von der toleranten Progressverbindung Adelphia zur pflichtschlagenden Burschenschaft in der Deutschen Burschen-schaft im Jahr 1933 keinen pl{\"o}tzlichen Bruch darstellte, sondern vielmehr die Folge einer langj{\"a}hrigen Entwicklung war, wobei der Erste Weltkrieg als be-sonders einschneidender Faktor zu bewerten ist. Am letztendlichen Art- und Dachverbandswechsel hatte auch Memmel einen entscheidenden Anteil. Dass nach der Umwandlung der waffenstudentischen Verbindungen in NS-Kameradschaften diese (auch Adelphia) w{\"a}hrend des Zweiten Weltkriegs teil-weise in W{\"u}rzburg im Verborgenen wiedererstehen konnten, hing auch mit der Patronage durch Memmel und sein imposantes Netzwerk zusammen. Den dritten Untersuchungskomplex dieser Arbeit bildet die kommunale Entwicklung von Groß- und Gauhauptst{\"a}dten im Dritten Reich, da sowohl W{\"u}rzburg als auch Halle eine solche verk{\"o}rperten. Ein Vergleich mit anderen St{\"a}dten unter denselben Voraussetzungen l{\"a}sst darauf schließen: Wer 1933/34 Oberb{\"u}rgermeister einer Groß- und Gauhauptstadt wurde, verdank-te dies nicht seiner Qualifikation. Die Nationalsozialisten, die dieses Amt er-hielten, bem{\"u}hten sich noch nicht einmal darum, es zu bekommen. Vielmehr stellten sie einen Kompromiss aus den jeweiligen lokalen Macht- und Interes-senskonstellationen dar. Eine Ausnahme hiervon bilden nur die wenigen St{\"a}dte, in denen bereits vor 1933 ein NSDAP-Angeh{\"o}riger als Stadtoberhaupt kandidiert hatte. Der Status der Gauhauptstadt f{\"u}hrte f{\"u}r die jeweiligen Oberb{\"u}rgermeister zu einem ganz besonderen Unterstellungsverh{\"a}ltnis, das sich als zweiseitiges Schwert entpuppte: Einerseits erhielt ihre Kommune spezielle F{\"o}rderung, andererseits standen sie unter einem hohem Erwar-tungsdruck, der sich vielerorts in einem schlechten Verh{\"a}ltnis von Oberb{\"u}r-germeister und Gauleiter manifestierte. Das Oberb{\"u}rgermeisteramt im Drit-ten Reich stellte aus beruflicher Sicht einen doppelten Bruch mit der Zeit vor 1933 dar: Zum einen konnte man ohne die bis dahin {\"u}blichen Qualifikationen zum Wahlbeamten einer Großstadt aufsteigen, andererseits bedeutete dies auch gleichzeitig das Karriereende.},
  subject      = {Geschichte},
  language  = {de}
}
@phdthesis{Birke2024,
  author    = {Birke, Claudius B.},
  title     = {Low Mach and Well-Balanced Numerical Methods for Compressible Euler and Ideal MHD Equations with Gravity},
  doi       = {10.25972/OPUS-36330},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363303},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Physical regimes characterized by low Mach numbers and steep stratifications pose severe challenges to standard finite volume methods. We present three new methods specifically designed to navigate these challenges by being both low Mach compliant and well-balanced. These properties are crucial for numerical methods to efficiently and accurately compute solutions in the regimes considered. First, we concentrate on the construction of an approximate Riemann solver within Godunov-type finite volume methods. A new relaxation system gives rise to a two-speed relaxation solver for the Euler equations with gravity. Derived from fundamental mathematical principles, this solver reduces the artificial dissipation in the subsonic regime and preserves hydrostatic equilibria. The solver is particularly stable as it satisfies a discrete entropy inequality, preserves positivity of density and internal energy, and suppresses checkerboard modes. The second scheme is designed to solve the equations of ideal MHD and combines different approaches. In order to deal with low Mach numbers, it makes use of a low-dissipation version of the HLLD solver and a partially implicit time discretization to relax the CFL time step constraint. A Deviation Well-Balancing method is employed to preserve a priori known magnetohydrostatic equilibria and thereby reduces the magnitude of spatial discretization errors in strongly stratified setups. The third scheme relies on an IMEX approach based on a splitting of the MHD equations. The slow scale part of the system is discretized by a time-explicit Godunov-type method, whereas the fast scale part is discretized implicitly by central finite differences. Numerical dissipation terms and CFL time step restriction of the method depend solely on the slow waves of the explicit part, making the method particularly suited for subsonic regimes. Deviation Well-Balancing ensures the preservation of a priori known magnetohydrostatic equilibria. The three schemes are applied to various numerical experiments for the compressible Euler and ideal MHD equations, demonstrating their ability to accurately simulate flows in regimes with low Mach numbers and strong stratification even on coarse grids.},
  subject      = {Magnetohydrodynamik},
  language  = {en}
}
@phdthesis{Krings2024,
  author    = {Krings, Moritz},
  title     = {Universit{\"a}re Psychiatrie um 1900 : Die Anfangsjahre der psychiatrischen Klinik in W{\"u}rzburg},
  doi       = {10.25972/OPUS-36140},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361407},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Ende des 19. Jahrhunderts standen sich in Deutschland zwei verschiedene Arten psychiatrischer Institutionen gegen{\"u}ber, die Anstaltspsychiatrien auf der einen, die universit{\"a}ren psychiatrischen Kliniken auf der anderen Seite. Die psychiatriehistorische Forschung widmete sich {\"u}berwiegend psychiatrischen Anstalten w{\"a}hrend Kliniken hier unterrepr{\"a}sentiert sind. Die vorliegende Arbeit m{\"o}chte zur historischen Kenntnis universit{\"a}rer psychiatrischer Einrichtungen beitragen. Hierzu werden die Charakteristika einer psychiatrischen Klinik um 1900 anhand des Beispiels der psychiatrischen Klinik der Universit{\"a}t W{\"u}rzburg betrachtet. Der Fokus liegt hierbei neben Lage und Aufbau der Klinik sowie deren Personal auf den drei Bereichen Patient*innen, Forschung und Lehre.},
  subject      = {Julius-Maximilians-Universit{\"a}t W{\"u}rzburg},
  language  = {de}
}
@phdthesis{Ramirez2024,
  author    = {Ramirez, Yesid A.},
  title     = {Structural basis of ubiquitin recognition and rational design of novel covalent inhibitors targeting Cdu1 from \(Chlamydia\) \(Trachomatis\)},
  doi       = {10.25972/OPUS-19168},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191683},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The WHO-designated neglected-disease pathogen Chlamydia trachomatis (CT) is a gram-negative bacterium responsible for the most frequently diagnosed sexually transmitted infection worldwide. CT infections can lead to infertility, blindness and reactive arthritis, among others. CT acts as an infectious agent by its ability to evade the immune response of its host, which includes the impairment of the NF-κB mediated inflammatory response and the Mcl1 pro-apoptotic pathway through its deubiquitylating, deneddylating and transacetylating enzyme ChlaDUB1 (Cdu1). Expression of Cdu1 is also connected to host cell Golgi apparatus fragmentation, a key process in CT infections. Cdu1 may this be an attractive drug target for the treatment of CT infections. However, a lead molecule for the development of novel potent inhibitors has been unknown so far. Sequence alignments and phylogenetic searches allocate Cdu1 in the CE clan of cysteine proteases. The adenovirus protease (adenain) also belongs to this clan and shares a high degree of structural similarity with Cdu1. Taking advantage of topological similarities between the active sites of Cdu1 and adenain, a target-hopping approach on a focused set of adenain inhibitors, developed at Novartis, has been pursued. The thereby identified cyano-pyrimidines represent the first active-site directed covalent reversible inhibitors for Cdu1. High-resolution crystal structures of Cdu1 in complex with the covalently bound cyano-pyrimidines as well as with its substrate ubiquitin have been elucidated. The structural data of this thesis, combined with enzymatic assays and covalent docking studies, provide valuable insights into Cdu1s activity, substrate recognition, active site pocket flexibility and potential hotspots for ligand interaction. Structure-informed drug design permitted the optimization of this cyano-pyrimidine based scaffold towards HJR108, the first molecule of its kind specifically designed to disrupt the function of Cdu1. The structures of potentially more potent and selective Cdu1 inhibitors are herein proposed. This thesis provides important insights towards our understanding of the structural basis of ubiquitin recognition by Cdu1, and the basis to design highly specific Cdu1 covalent inhibitors.},
  subject      = {Ubiquitin},
  language  = {en}
}
@phdthesis{Schulz2024,
  author    = {Schulz, Daniel},
  title     = {Development of Inhibitory Control in Kindergarten Children},
  doi       = {10.25972/OPUS-35715},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357152},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {This dissertation explores the development and assessment of inhibitory control - a crucial component of executive functions - in young children. Inhibitory control, defined as the ability to suppress inappropriate responses (Verbruggen \& Logan, 2008), is essential for adaptable and goal-oriented behavior. The rapid and non-linear development of this cognitive function in early childhood presents unique challenges for accurate assessment. As children age, they often exhibit a ceiling effect in terms of response accuracy (Petersen et al., 2016), underscoring the need to consider response latency as well. Ideally, combining response latency with accuracy could yield a more precise measure of inhibitory control (e.g., Magnus et al., 2019), facilitating a detailed tracking of developmental changes in inhibitory control across a wider age spectrum. The three studies of this dissertation collectively aim to clarify the relationship between response accuracy, response latency, and inhibitory control across different stages of child development. Each study utilizes a computerized Pointing Stroop Task (Berger et al., 2000) to measure inhibitory control, examining the task's validity and the integration of dual metrics for a more comprehensive evaluation. The first study focuses on establishing the validity of using both response accuracy and latency as indicators of inhibitory control. Utilizing the framework of explanatory item-response modeling (De Boeck \& Wilson, 2004), the study revealed how the task characteristics congruency and item position influence both the difficulty level and timing aspects in young children's responses in the computerized Pointing Stroop task. Further, this study found that integrating response accuracy with latency, even in a basic manner, provides additional insights. Building upon these findings, the second study investigates the nuances of integrating response accuracy and latency, examining whether this approach can account for age-related differences in inhibitory control. It also explores whether response latencies may contain different information depending on the age and proficiency of the children. The study leverages novel and established methodological perspectives to integrate response accuracy and latency into a single metric, showing the potential applicability of different approaches for assessing inhibitory control development. The third study extends the investigation to a longitudinal perspective, exploring the dynamic relationship between response accuracy, latency, and inhibitory control over time. It assesses whether children who achieve high accuracy at an earlier age show faster improvement in response latency, suggesting a non-linear maturation pathway of inhibitory control. The study also examines if the predictive value of early response latency for later fluid intelligence is dependent on the response accuracy level. Together, these empirical studies contribute to a more robust understanding of the complex interaction between inhibitory control, response accuracy, and response latency, facilitating valid evaluations of cognitive capabilities in children. Moreover, the findings may have practical implications for designing educational strategies and clinical interventions that address the developmental trajectory of inhibitory control. The nuanced approach advocated in this dissertation suggests prioritizing accuracy in assessment and interventions during the early stages of children's cognitive development, gradually shifting the focus to response latency as children mature and secure their inhibitory control abilities.},
  subject      = {Kognitive Entwicklung},
  language  = {en}
}
@phdthesis{Bossert2024,
  author    = {Bossert, Patrick},
  title     = {Statistical structure and inference methods for discrete high-frequency observations of SPDEs in one and multiple space dimensions},
  doi       = {10.25972/OPUS-36113},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361130},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The focus of this thesis is on analysing a linear stochastic partial differential equation (SPDE) with a bounded domain. The first part of the thesis commences with an examination of a one-dimensional SPDE. In this context, we construct estimators for the parameters of a parabolic SPDE based on discrete observations of a solution in time and space on a bounded domain. We establish central limit theorems for a high-frequency asymptotic regime, showing substantially smaller asymptotic variances compared to existing estimation methods. Moreover, asymptotic confidence intervals are directly feasible. Our approach builds upon realized volatilities and their asymptotic illustration as the response of a log-linear model with a spatial explanatory variable. This yields efficient estimators based on realized volatilities with optimal rates of convergence and minimal variances. We demonstrate our results by Monte Carlo simulations. Extending this framework, we analyse a second-order SPDE model in multiple space dimensions in the second part of this thesis and develop estimators for the parameters of this model based on discrete observations in time and space on a bounded domain. While parameter estimation for one and two spatial dimensions was established in recent literature, this is the first work that generalizes the theory to a general, multi-dimensional framework. Our methodology enables the construction of an oracle estimator for volatility within the underlying model. For proving central limit theorems, we use a high-frequency observation scheme. To showcase our results, we conduct a Monte Carlo simulation, highlighting the advantages of our novel approach in a multi-dimensional context.},
  subject      = {Stochastische partielle Differentialgleichung},
  language  = {en}
}
@phdthesis{Daum2024,
  author    = {Daum, Stefanie},
  title     = {Nahrhafte Momente schaffen - Sinnbildgest{\"u}tzte Interviews (SigI) im Fallverstehen bei Lernbeeintr{\"a}chtigungen unter Ber{\"u}cksichtigung entwicklungsp{\"a}dagogischer Aspekte im K{\"o}nnen, Wissen und Wollen},
  doi       = {10.25972/OPUS-36035},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360351},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In den letzten Jahren stieg die Anzahl an f{\"o}rderbed{\"u}rftigen Sch{\"u}lern sowie an Sch{\"u}lern mit einer Migrations- bzw. Fluchtgeschichte an der Berufsschule. Damit entsteht eine neue Sch{\"u}lerklientel, die von einer hohen Sch{\"u}lerheterogenit{\"a}t und Lernstanddifferenz gepr{\"a}gt ist. Vermehrt sind auch eine sprachliche Armut sowie Lernbeeintr{\"a}chtigungen zu beobachten. Die Arbeit mit Sinnbildern im diagnostischen Prozess bei Lernbeeintr{\"a}chtigungen ist ein kleiner Baustein auf dem Weg dorthin, dass Lernen und damit auch ein Sich-Weiterentwickeln gelingen kann. Dabei pr{\"a}sentiert sich das l{\"o}sungs- sowie entwicklungsorientierte Verfahren als eine in Beziehung zueinander stehenden Einheit aus Lernbeeintr{\"a}chtigung, potenzielle L{\"o}sung und nahrhaften Boden. Lernbeeintr{\"a}chtigung: Der Trias liegt die Annahme zugrunde, dass der Lernprozess des Sch{\"u}lers gestoppt ist. Wenngleich der Sch{\"u}ler sp{\"u}rt, dass da etwas ist, das ihm beim Lernen im Weg steht, so ist er jedoch nicht in der Lage das Gesp{\"u}rte zu verbalisieren. Nahrhafter Boden: Mit Hilfe eines von Sinnbildern gest{\"u}tzten Interviews soll es gelingen, die vagen Vermutungen der Sch{\"u}ler hinsichtlich ihrer Lernbeeintr{\"a}chtigung zu versprachlichen. Dabei spielt die von den Bildern ausgehende Resonanz eine entscheidende Rolle. Durch sie k{\"o}nnen dem Sch{\"u}ler eigene implizite Denk- und Handlungsmuster gedanklich zug{\"a}nglich gemacht und versprachlicht werden. Potenzielle L{\"o}sung: Die im Rahmen des Sinnbildgest{\"u}tzten Interviews in Erfahrung gebrachten Informationen erm{\"o}glichen im besten Fall eine Sicht darauf, was dem Sch{\"u}ler in seinem gestoppten Lernprozess im Weg steht. Dabei geht es nicht darum eine kausale Ursache zu finden, sondern eine prozessorientierte sowie l{\"o}sungsorientierte Sichtweise einzunehmen. Die Versprachlichung der vagen Vermutungen erm{\"o}glicht ein Arbeiten mit dem Wissen in der realen Welt. Im Falle von Gelingen, kann der Interviewf{\"u}hrende die durch das Sinnbildgest{\"u}tzte Interview in Erfahrung gebrachten Lernbeeintr{\"a}chtigungen innerhalb der drei Lerndimensionen im K{\"o}nnen, Wissen und Wollen (Ellinger/Hechler 2021) verorten, um eine individuelle -auf die Lernbeeintr{\"a}chtigung zugeschnittene- Lernhilfe zu generieren.},
  subject      = {Symbol},
  language  = {de}
}
@phdthesis{Hegmann2024,
  author    = {Hegmann, Reinhold},
  title     = {Pr{\"u}ferqualifikation und Pr{\"u}fungsqualit{\"a}t - Eine empirische Untersuchung privater pr{\"u}fungspflichtiger Unternehmen in Deutschland},
  doi       = {10.25972/OPUS-32254},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322546},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die Jahresabschlusspr{\"u}fung verfolgt das Ziel, die Verl{\"a}sslichkeit der Rechnungslegung zu best{\"a}tigen. Folglich kann sie einen wesentlichen Beitrag zu einem hohen Informationsniveau an den M{\"a}rkten leisten. Angesichts dieser großen {\"o}konomischen Bedeutung unternimmt der deutsche Gesetzgeber zahlreiche Anstrengungen, um eine hohe Pr{\"u}fungsqualit{\"a}t sicherzustellen. Die Sichtung der Wirtschaftspr{\"u}ferordnung zeigt hierbei, dass regulatorische Maßnahmen ergriffen werden, die am Kern der Jahresabschlusspr{\"u}fung ansetzen, n{\"a}mlich an den Berufsangeh{\"o}rigen selbst. So wurde der Zugang zum Berufsstand der vereidigten Buchpr{\"u}fer mehrmals geschlossen und wiederer{\"o}ffnet. Des Weiteren sind markante Anpassungen des Niveaus des Wirtschaftspr{\"u}fungsexamens im Zeitablauf zu erkennen. Bei der Jahresabschlusspr{\"u}fung der Unternehmen von {\"o}ffentlichem Interesse sind außerdem besondere Berufspflichten zu erf{\"u}llen. Zum einen ist diesen schweren Eingriffen in die Freiheit der Berufswahl und der Berufsaus{\"u}bung gemein, dass sie allesamt die Qualifikation des Abschlusspr{\"u}fers adressieren. Zum anderen werden die entsprechenden Gesetzes{\"a}nderungen mehrheitlich mit einer St{\"a}rkung der Pr{\"u}fungsqualit{\"a}t begr{\"u}ndet. Fraglich ist, inwiefern jene Facetten der Pr{\"u}ferqualifikation tats{\"a}chlich einen Einfluss auf die Pr{\"u}fungsqualit{\"a}t aus{\"u}ben. Aufgrund mangelnder Evidenz ergibt sich die Notwendigkeit, eine empirische Studie am deutschen Pr{\"u}fermarkt durchzuf{\"u}hren und somit den Beginn zur Schließung der identifizierten Forschungsl{\"u}cke zu setzen. Das Ziel der vorliegenden Dissertation besteht folglich darin, den Zusammenhang zwischen der Pr{\"u}ferqualifikation und der Pr{\"u}fungsqualit{\"a}t mittels Regressionsanalysen zu untersuchen. Dazu wurde ein einzigartiger Datensatz zu deutschen privaten pr{\"u}fungspflichtigen Kapitalgesellschaften mit unkonsolidierten Finanz- und Pr{\"u}ferinformationen im Zeitraum 2006-2018 mit insgesamt 217.585 grundlegenden Beobachtungen erhoben, bereinigt und aufbereitet. Da die Pr{\"u}fungsqualit{\"a}t nicht direkt beobachtbar ist, wird zwischen wahrgenommener Pr{\"u}fungsqualit{\"a}t und tats{\"a}chlicher Pr{\"u}fungsqualit{\"a}t unterschieden. Im Rahmen dieser Dissertation wird die wahrgenommene Pr{\"u}fungsqualit{\"a}t {\"u}ber Fremdkapitalkosten und die tats{\"a}chliche Pr{\"u}fungsqualit{\"a}t {\"u}ber absolute diskretion{\"a}re Periodenabgrenzungen approximiert. Die Ergebnisse der Hauptregressionen zeigen {\"u}berwiegend, dass kein Zusammenhang zwischen den Maßgr{\"o}ßen der Pr{\"u}ferqualifikation und der wahrgenommenen und tats{\"a}chlichen Pr{\"u}fungsqualit{\"a}t besteht. Die Zusatz- und Sensitivit{\"a}tsanalysen unterst{\"u}tzen diesen Befund. So k{\"o}nnen mit Blick auf die Berufszugangsregelungen keine Qualit{\"a}tsunterschiede zwischen den Berufsst{\"a}nden der Wirtschaftspr{\"u}fer und der vereidigten Buchpr{\"u}fer nachgewiesen werden. Auch innerhalb des Berufstandes der Wirtschaftspr{\"u}fer ergeben sich keine Hinweise auf ein Qualit{\"a}tsgef{\"a}lle zwischen den Pr{\"u}fergruppen, die unterschiedliche Examensanforderungen durchlebt haben. Hinsichtlich der Berufsaus{\"u}bungsregelungen ist zu beobachten, dass die zus{\"a}tzlichen Anforderungen an die Jahresabschlusspr{\"u}fung der Unternehmen von {\"o}ffentlichem Interesse nicht mit einer anderen Pr{\"u}fungsqualit{\"a}t bei privaten Unternehmen verbunden sind. Die beschriebenen regulatorischen Schritte des Gesetzgebers im Bereich der Pr{\"u}ferqualifikation erscheinen somit im Lichte einer verbesserten Pr{\"u}fungsqualit{\"a}t nicht zwingend gerechtfertigt.},
  subject      = {Pr{\"u}fungsqualit{\"a}t},
  language  = {de}
}
@phdthesis{Wagner2024,
  author    = {Wagner, Tim Matthias},
  title     = {Characterization of 2D antimony lattices},
  doi       = {10.25972/OPUS-36329},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363292},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Two-dimensional lattices are in the focus of research in modern solid state physics due to their novel and exotic electronic properties with tremendous potential for seminal future applications. Of particular interest within this research field are quantum spin Hall insulators which are characterized by an insulating bulk with symmetry-protected metallic edge states. For electrons within these one-dimensional conducting channels, spin-momentum locking enables dissipationless transport - a property which promises nothing short of a revolution for electronic devices. So far, however, quantum spin Hall materials require enormous efforts to be realized such as cryogenic temperatures or ultra-high vacuum. A potential candidate to overcome these shortcomings are two-dimensional lattices of the topological semi-metal antimony due to their potential to host the quantum spin Hall effect while offering improved resilience against oxidation. In this work, two-dimensional lattices of antimony on different substrates, namely Ag(111), InSb(111) and SiC(0001), are investigated regarding their atomic structure and electronic properties with complimentary surface sensitive techniques. In addition, a systematic oxidation study compares the stability of Sb-SiC(0001) with that of the two-dimensional topological insulators bismuthene-SiC(0001) and indenene-SiC(0001). A comprehensive experimental analysis of the \((\sqrt{3}\times\sqrt{3})R30^\circ\) Sb-Ag(111) surface, including X-ray standing wave measurements, disproves the proclaimed formation of a buckled antimonene lattice in literature. The surface lattice can instead be identified as a metallic Ag\(_2\)Sb surface alloy. Antimony on InSb(111) shows an unstrained Volmer-Weber island growth due to its large lattice mismatch to the substrate. The concomitant moir\'{e} situation at the interface imprints mainly in a periodic height corrugation of the antimony islands which as observed with scanning tunneling microscopy. On islands with various thicknesses, quasiparticle interference patterns allow to trace the topological surface state of antimony down to the few-layer limit. On SiC(0001), two different two-dimensional antimony surface reconstructions are identified. Firstly, a metallic triangular \$1\times1\$ lattice which constitutes the antimony analogue to the topological insulator indenene. Secondly, an insulating asymmetric kagome lattice which represents the very first realized atomic surface kagome lattice. A comparative, systematic oxidation study of elemental (sub-)monolayer materials on SiC(0001) reveals a high sensitivity of indenene and bismuthene to small dosages of oxygen. An improved resilience is found for Sb-SiC(0001) which, however, oxidizes nevertheless if exposed to oxygen. These surface lattices are therefore not suitable for future applications without additional protective measures.},
  subject      = {Antimon},
  language  = {en}
}
@phdthesis{Koerner2024,
  author    = {K{\"o}rner, Jacob},
  title     = {Theoretical and numerical analysis of Fokker-Planck optimal control problems by first- and second-order optimality conditions},
  doi       = {10.25972/OPUS-36299},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362997},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In this thesis, a variety of Fokker--Planck (FP) optimal control problems are investigated. Main emphasis is put on a first-- and second--order analysis of different optimal control problems, characterizing optimal controls, establishing regularity results for optimal controls, and providing a numerical analysis for a Galerkin--based numerical scheme. The Fokker--Planck equation is a partial differential equation (PDE) of linear parabolic type deeply connected to the theory of stochastic processes and stochastic differential equations. In essence, it describes the evolution over time of the probability distribution of the state of an object or system of objects under the influence of both deterministic and stochastic forces. The FP equation is a cornerstone in understanding and modeling phenomena ranging from the diffusion and motion of molecules in a fluid to the fluctuations in financial markets. Two different types of optimal control problems are analyzed in this thesis. On the one hand, Fokker--Planck ensemble optimal control problems are considered that have a wide range of applications in controlling a system of multiple non--interacting objects. In this framework, the goal is to collectively drive each object into a desired state. On the other hand, tracking--type control problems are investigated, commonly used in parameter identification problems or stemming from the field of inverse problems. In this framework, the aim is to determine certain parameters or functions of the FP equation, such that the resulting probability distribution function takes a desired form, possibly observed by measurements. In both cases, we consider FP models where the control functions are part of the drift, arising only from the deterministic forces of the system. Therefore, the FP optimal control problem has a bilinear control structure. Box constraints on the controls may be present, and the focus is on time--space dependent controls for ensemble--type problems and on only time--dependent controls for tracking--type optimal control problems. In the first chapter of the thesis, a proof of the connection between the FP equation and stochastic differential equations is provided. Additionally, stochastic optimal control problems, aiming to minimize an expected cost value, are introduced, and the corresponding formulation within a deterministic FP control framework is established. For the analysis of this PDE--constrained optimal control problem, the existence, and regularity of solutions to the FP problem are investigated. New \$L^\infty\$--estimates for solutions are established for low space dimensions under mild assumptions on the drift. Furthermore, based on the theory of Bessel potential spaces, new smoothness properties are derived for solutions to the FP problem in the case of only time--dependent controls. Due to these properties, the control--to--state map, which associates the control functions with the corresponding solution of the FP problem, is well--defined, Fr{\´e}chet differentiable and compact for suitable Lebesgue spaces or Sobolev spaces. The existence of optimal controls is proven under various assumptions on the space of admissible controls and objective functionals. First--order optimality conditions are derived using the adjoint system. The resulting characterization of optimal controls is exploited to achieve higher regularity of optimal controls, as well as their state and co--state functions. Since the FP optimal control problem is non--convex due to its bilinear structure, a first--order analysis should be complemented by a second--order analysis. Therefore, a second--order analysis for the ensemble--type control problem in the case of \$H^1\$--controls in time and space is performed, and sufficient second--order conditions are provided. Analogous results are obtained for the tracking--type problem for only time--dependent controls. The developed theory on the control problem and the first-- and second--order optimality conditions is applied to perform a numerical analysis for a Galerkin discretization of the FP optimal control problem. The main focus is on tracking-type problems with only time--dependent controls. The idea of the presented Galerkin scheme is to first approximate the PDE--constrained optimization problem by a system of ODE--constrained optimization problems. Then, conditions on the problem are presented such that the convergence of optimal controls from one problem to the other can be guaranteed. For this purpose, a class of bilinear ODE--constrained optimal control problems arising from the Galerkin discretization of the FP problem is analyzed. First-- and second--order optimality conditions are established, and a numerical analysis is performed. A discretization with linear finite elements for the state and co--state problem is investigated, while the control functions are approximated by piecewise constant or piecewise quadratic continuous polynomials. The latter choice is motivated by the bilinear structure of the optimal control problem, allowing to overcome the discrepancies between a discretize--then--optimize and optimize--then--discretize approach. Moreover, second--order accuracy results are shown using the space of continuous, piecewise quadratic polynomials as the discrete space of controls. Lastly, the theoretical results and the second--order convergence rates are numerically verified.},
  subject      = {Parabolische Differentialgleichung},
  language  = {en}
}
@phdthesis{Kappes2024,
  author    = {Kappes, Alexander},
  title     = {High-Redshift Blazars Observed by the International LOFAR Telescope},
  doi       = {10.25972/OPUS-36144},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361444},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {This work presents the first ILT observations of high redshift blazars and their study in terms of jet evolution, morphology, and interaction with the surrounding medium. Each of these represents a highly topical area of astronomywith a large number of open questions. To better understand Active Galactic Nuclei (AGN) and their fundamental inner workings, new techniques are needed to exploit the full potential of the next generation of radio interferometers. Some of these tools are presented here and applied to one of the latest generation of software radio telescopes. A major focus of the studies presented is on the unification model, where the observed blazars are discussed for their properties to be rotated counterparts of Fanaroff-Riley Class II (FR-II) radio galaxies, when classified as Flat Spectrum Radio Quasars (FSRQs). In addition, multiwavelength information has been included in the analysis. Both studies are feasibility studies that will serve as a basis for future similar studies. The characteristics discussed and their interpretation do not allow conclusions to be drawn for their respective populations. However, by applying them to a larger number of targets, population studies will be possible. The first chapters introduce the necessary topics, AGN, principles of radio observations and ILT, in the necessary depth to provide the reader with a solid knowledge base. They are particularly important for understanding the current limits and influences of uncertainties in the observation, calibration and imaging process. But they also shed light on realistic future improvements. A particular focus is on the development and evolution of the LOw-Frequency ARray (LOFAR)-Very Long Baseline Interferometry (VLBI) pipeline. With the tools at hand, the first study addresses the high redshift blazar S5 0836+710 \$(z=2.218)\$, which has been observed at various wavelengths and resolutions. It has a disrupted one-sided jet with an associated extended region further out. Despite the excellent wavelength coverage, only the additional ILT observations provided a complete picture of the source. With the data, the extended region could be classified as a hotspot moving at slightly relativistic speeds.. With the ILT data it was also possible to extract the flux of the core region of the AGN, and in projection to reveal the mixed counter-hotspot behind it. This also allowed constraints on jet parameters and environmental properties to be modelled, which were previously inconclusive. Technically, this study shows that the ILT can be used as an effective VLBI array for compact sources with small angular scales. However, the detection of faint components beyond redshifts of \$z=2\$ may require the capabilities of the Square Kilometre Array (SKA) to provide a significant number of detections to enable statistical conclusions. The second study uses a much improved calibration pipeline to analyse the high redshift blazar GB1508+5714 \$(z=4.30)\$. The ILT data revealed a previously unseen component in the eastern direction. A spectral index map was generated from the Karl G. Jansky Very Large Array (VLA) data, showing spectral index values of \$-1.2_{-0.2}^{+0.4}\$ for the western component, steeper than \$-1.1\$ for the eastern region, and \$0.023 \pm 0.007\$ for the core. Using the information provided by the ILT observation, as well as multi-wavelength information from other observations ranging from the long radio wavelengths to the \$\gamma\$ regime, four models were developed to interpret the observed flux with different emission origins. This also allowed to test a proposed interaction channel of the electrons provided by the jet, to cool off via inverse compton scattering with the Cosmic Microwave Background (CMB) photons, rather than by the usual synchrotron emission. This is referred to as cmb quenching in the literature, which could be shown in the study, to be necessary in any case. Finally, one of the four models was considered in which the hotspots in the detected components are unresolved and mixed by the lobe emission, with the X-ray emission coming from the lobes and partially mixed by the bright core region. The results of this preferred model are consistent with hotspots in a state of equipartition and lobes almost so. The study shows that high redshift blazars can be studied with the ILT, and expanding the sample of high redshift blazars resolved at multiple frequencies will allow a statistical study of the population. Finally, this work successfully demonstrates the powerful capabilities of the ILT to address questions that were previously inaccessible. The current state of the LOFAR-VLBI pipeline, when properly executed, allows work on the most challenging objects and will only improve in the future. In particular, this gives a glimpse of the possibilities that SKA will bring to astronomy.},
  subject      = {Blazar},
  language  = {en}
}
@phdthesis{Zuber2024,
  author    = {Zuber, Jonas Maximilian},
  title     = {Evaluation von Sedierungen und Allgemeinan{\"a}sthesien zur Durchf{\"u}hrung bildgebender Verfahren bei S{\"a}uglingen bis zum 6. Lebensmonat},
  doi       = {10.25972/OPUS-36111},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361111},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Vorliegende Untersuchung am Universit{\"a}tsklinikum W{\"u}rzburg sowie die Befragung von An{\"a}sthesisten/An{\"a}sthesistinnen im Raum der 3 DACH-L{\"a}nder zeigen, dass bildgebende Verfahren bei S{\"a}uglingen mit einer niedrigen Rate an Komplikationen, zumeist in medikament{\"o}ser Sedierung mit Propofol, durchgef{\"u}hrt werden. Wie international {\"u}blich ist im S{\"a}uglingsalter die Magnetresonanztomographie das bildgebende Verfahren der Wahl und wird, mit {\"u}berzeugender H{\"a}ufigkeit, erfolgreich durchgef{\"u}hrt. Die Untersuchung am Universit{\"a}tsklinikum W{\"u}rzburg legt nahe, dass m{\"a}nnliche S{\"a}uglinge h{\"a}ufiger eine Bildgebung ben{\"o}tigen und h{\"a}ufiger h{\"o}heren ASA-Kategorie zugeschrieben werden. Dabei scheinen sie auch h{\"a}ufiger Komplikationen zu erleben und bed{\"u}rfen daher besonderer Aufmerksamkeit. Eine eventuelle Alternative zur Sedierung kann dabei die „feed-and-sleep" Methode darstellen. In unserer Umfrage konnten wir erheben, dass diese Methode bisher wenig verbreitet ist, obwohl in diesem Zusammenhang eventuell Abl{\"a}ufe und Prozesszeiten strukturiert und optimiert werden k{\"o}nnen, da beispielsweise die Nach{\"u}berwachung entf{\"a}llt. Vorstellbar w{\"a}re beispielsweise, mehrere S{\"a}uglinge zum gleichen Zeitpunkt ins MRT zu bestellen, um gegebenenfalls den am fr{\"u}hesten eingeschlafenen S{\"a}ugling vorzuziehen. Diese Methode sollte zuk{\"u}nftig Einzug in die wissenschaftliche Untersuchung von bildgebenden Verfahren bei S{\"a}uglingen finden. Die Umfrage im deutschsprachigen Raum zeigt eine Leitlinien-gerechte Betreuung von S{\"a}uglingen f{\"u}r bildgebende Verfahren, die mit einer hohen Qualit{\"a}t, und zumeist erfolgreich von erfahrenen An{\"a}sthesisten/An{\"a}sthesistinnen durchgef{\"u}hrt wird. Eventuelle Verbesserungen k{\"o}nnen im Bereich der Ausbildung nachfolgender {\"A}rztinnen/{\"A}rzte und in der h{\"a}ufigeren Verwendung der „feed-and-sleep" Methode liegen, die vielen Kollegen/Kolleginnen bekannt ist, aber nur selten durchgef{\"u}hrt wird. Ziel ist eine qualitativ hochwertige, schnellstm{\"o}glich durchgef{\"u}hrte Bildgebung, die ohne oder mit der niedrigst m{\"o}glichen Dosierung eines sedierenden Medikamentes zu erreichen ist.},
  subject      = {Sedierung},
  language  = {de}
}
@phdthesis{Fischer2024,
  author    = {Fischer, Jonas Maria},
  title     = {Ph{\"a}notyp und Funktion von Follikul{\"a}ren Helfer Zell-{\"a}hnlichen T-Zellen im entz{\"u}ndeten Gelenk von Patientinnen und Patienten mit Juveniler Idiopathischer Arthritis},
  doi       = {10.25972/OPUS-36302},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363022},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Innerhalb der Juvenilen Idiopathischen Arthritis (JIA) bilden Patienten mit Antinukle{\"a}ren Antik{\"o}rpern (ANA) Subgruppen-{\"u}bergreifend eine klinisch homogene Erkrankungsgruppe. Ob diesen klinischen Gemeinsamkeiten jedoch auch eine einheitliche Pathogenese zugrunde liegt, ist bisher unbekannt. Sogenannte periphere T-Helferzellen (TPH) spielen im Kontext zahlreicher Autoimmunerkrankungen eine entscheidende Rolle bei der Aktivierung autoreaktiver B-Zellen. Ziel dieser Arbeit war daher die ph{\"a}notypische und funktionelle Analyse von PD-1hiCXCR5-CD4+ TPH-Zellen, sowie deren Verteilung in der Synovialfl{\"u}ssigkeit von Patienten unterschiedlicher Subgruppen der JIA. Hierzu wurden Ph{\"a}notyp und Zytokinprofil von PD-1hiCD4+ T-Zellen durchflusszytometrisch analysiert. Der funktionelle Einfluss von PD-1hiCD4+ T-Zellen auf die B-Zell-Differenzierung wurde mittels in vitro Kokulturen FACS-sortierter TPH-Zellen der Synovialfl{\"u}ssigkeit untersucht. IL-21- und IL-17-produzierende T-Ged{\"a}chtniszellen der Synovialfl{\"u}ssigkeit zeigten eine negative Korrelation zueinander. Die IL-21-Produktion ging besonders von PD-1hiCXCR5-HLA-DR+CD4+ T-Zellen aus, welche besonders in den Gelenken ANA-positiver JIA-Patienten akkumulierten. Diese Population zeigte ph{\"a}notypische {\"A}hnlichkeit mit TPH-Zellen und leistete in vitro effiziente B-Zell-Hilfe zu Plasmazelldifferenzierung und Immunglobulinsekretion, induzierte jedoch zudem einen CD21lo/-CD11c+T-bet+ Ph{\"a}notyp in B-Zellen. Passend hierzu bestand auch ex vivo eine signifikante Korrelation zwischen TPH und CD21lo/-CD11c+T-bet+ doppelt-negativen B-Zellen (BDN). Es konnte also die Expansion einer spezifischen T-Zellpopulation mit ph{\"a}notypischen und funktionellen Charakteristika von TPH-Zellen beobachtet und deren funktioneller Zusammenhang mit CD21lo/-CD11c+T-bet+ BDN in der Synovialfl{\"u}ssigkeit von JIA-Patienten aufgezeigt werden. Dies k{\"o}nnte die Autoimmunantwort auf ubiquit{\"a}re Autoantigene innerhalb betroffener Gelenke ANA-positiver JIA-Patienten widerspiegeln.},
  subject      = {Rheumatologie},
  language  = {de}
}
@phdthesis{Swain2024,
  author    = {Swain, Asim},
  title     = {Helically Twisted Graphene Nanoribbons: Bottom-up Stereospecific Synthesis and Characterization},
  doi       = {10.25972/OPUS-36016},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360164},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Over the past decade, substantial progress has been made in synthesizing atomically precise carbon nanostructures, with a focus on graphene nanoribbons (NRs) through advanced synthetic techniques. Despite these advancements, precise control over the stereochemistry of twisted NRs remains challenging. This thesis introduces a strategic approach to achieve absolute control over the single-handed helical conformation in a cove-edged NR, utilizing enantiopure [n]helicenes as a molecular wrench to intricately dictate the overall conformation of the NR. Enantiopure [7]helicenes were stitched to the terminal K-regions of a conjugated pyrene NR using a stereospecific and site-selective palladium(II)-catalyzed annulative π-extension (APEX) reaction, resulting in a helically twisted NR with an end-to-end twist of 171°, the second-largest twist reported so far in the literature for twistacenes. The helical end-to-end twist increases with each addition of benzene ring to the central acene core, suggesting that the extra strain induced by the terminal [7]helicenes maintains such a high level of twist. The quantum chemical calculations were conducted to investigate the impact of twisting on the conformational population. At room temperature, the central backbone of the nanoribbon adopts the twisted helicity opposite to that of the attached [7]helicene, constituting around 99\% of the molecular population. For instance, (P)-[7]helicenes produce a left-handed helical nanoribbon, while (M)-[7]helicenes produce a right-handed helical nanoribbon. In the presence of helicenes of opposite chirality, the nanoribbon adopts a waggling conformation. The helically twisted nanoribbons are conformationally robust, as variable temperature chiroptical measurements showed no change in CD and CPL spectra. The proposed strategy, involving the late-stage addition of [n]helicene units through the APEX reaction, appears promising for streamlining the synthesis of diverse cove edge NR variants with desired conformations. In addition to single-handed helically twisted nanoribbons, the symmetry-based functional properties of C2 and C1 symmetric pyrene-fused single and double [n]helicene compounds were studied. Owing to its higher structural rigidity, the C1 symmetric heptagonal ring-containing molecules exhibited exceptional configurational stability along with remarkable chiroptical properties compared to their C2 symmetric as well as pristine helicene congeners.},
  subject      = {Helicene},
  language  = {en}
}
@phdthesis{deSunda2024,
  author    = {de Sunda, Angela},
  title     = {Effekte der Tiefenhirnstimulation bei Patienten mit idiopathischem Parkinson-Syndrom auf Symptome der Stimme und des Sprechens},
  doi       = {10.25972/OPUS-36301},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363014},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Sprech- und Stimmst{\"o}rungen sind h{\"a}ufige Symptome der Idiopathischen Parkinson Erkrankung (IPS), wobei bis zu 89\% der Patienten im Verlauf der Krankheit unter einer Dysarthrie leiden. Die Tiefenhirnstimulation des Nucleus subthalamicus (STN-DBS) ist eine etablierte Behandlung f{\"u}r die motorischen Symptome des IPS (Allert et al., 2004). W{\"a}hrend STN-DBS positive Effekte auf einige Teilfunktionsbereiche der Dysarthrie zu haben scheint, berichten die meisten Studien entweder {\"u}ber keine Verbesserung oder eine Verschlechterung der Sprech- und Stimmfunktionen nach Implantation der STN-DBS (Tsuboi et al., 2015; Wang et al., 2003; Wertheimer et al., 2014). Klinische Erfahrungswerte sowie Fallberichte und Studien lassen vermuten, dass diese sprachtherapeutisch relevanten Nebenwirkungen unabh{\"a}ngig von der therapeutischen Wirksamkeit der STN-DBS sind und daher als unerw{\"u}nschte, aber nicht therapieimmanente Interferenzfaktoren anzusehen sind (Bouthour et al., 2018), die es genauer zu untersuchen gilt, da die Lebensqualit{\"a}t von IPS-Erkrankten als stark einschr{\"a}nkend wahrgenommen wird (Hariz et al., 2010). Eine aufwendige und methodisch fundierte Klassifizierung wurde von Tsuboi und Kollegen vorgenommen, die im Zusammenhang mit STN-DBS f{\"u}nf Cluster von Sprech- und Stimmst{\"o}rungen identifizierten (Tanaka et al., 2020; Tsuboi et al., 2015, 2017). Dazu z{\"a}hlten die Ph{\"a}notypen „spastische Dysarthrie", „Stottern", „rigid-hypokinetischer Typ", „behauchte Stimme" und „gepresste Stimme". Erste Hinweise lassen darauf schließen, dass die Nebenwirkungen von STN-DBS auf die Stimulation spezifischer Gehirnkreise zur{\"u}ckzuf{\"u}hren sein k{\"o}nnte (Fox et al., 2014). In dieser Arbeit wird eine retrospektive Studie mit STN-DBS stimulierten IPS Erkrankten vorgestellt, die sprachtherapeutisch relevante Sprech- und Stimmst{\"o}rungen unter zwei Bedingungen bewertet (ein- und ausgeschaltete Stimulation) sowie eine prospektive Studie mit den beiden gleichen Bedingungen. Beide Studien haben das Ziel einer Replizierbarkeit der Ergebnisse von Tsuboi et al. (2015, 2017). Die zweite prospektive Studie bezieht außerdem konnektombasierte Daten ein. Die Ergebnisse beider Studien lassen quantitativ keine Signifikanzen hinsichtlich der o.g. dysarthrischen Ph{\"a}notypen zu, quantitativ lassen sich jedoch deutliche Tendenzen {\"a}hnlich der Ausgangsstudie erkennen. Zudem wurden das Cluster „Stottern" in der retrospektiven Studie als weiteres m{\"o}glicherweise STN-DBS immantentes Cluster identifiziert. In der prospektiven Studie wurde ein Cluster hinzugef{\"u}gt, da in den Beurteilungen zus{\"a}tzlich die Symptomatik „hasty speech" oder auch „hastiges Sprechen" beobachtet wurde.},
  subject      = {Dysarthrie},
  language  = {de}
}
@phdthesis{Roger2024,
  author    = {Roger, Chantal},
  title     = {Photophysics and Spin Chemistry of Triptycene Bridge Donor-Acceptor-Triads},
  doi       = {10.25972/OPUS-36303},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363031},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The goal of this thesis was to investigate the influence of rotational restriction between individual parts and of the varying electron density in the bridging unit of D B A systems on the exchange interaction 2J, and thus the electronic coupling between a donor state and an acceptor state. A better understanding of how to influence the underlaying spin dynamics in such donor acceptor systems can open up the door to new technologies, such as modern molecular electronics or optoelectronic devices. Therefore, three series of molecules consisting of a TAA electron donor, a TTC or ATC bridging unit and a PDI electron acceptor were studied. To investigate the influence of rotational restriction on 2J and the electronic coupling, a series of four rotationally hindered triads (chapter 6) was synthesised. The dihedral angle between the TAA and the TTC as well as between the TTC and the PDI was restricted by ortho methyl groups at the phenylene linkers of the connecting ends to the TTC bridge, producing a twist around the linking single bond which minimises the π overlap. The triads exhibit varying numbers of ortho methyl groups and therefore different degrees of rotational restriction. In order to shine light on the influence of varying electron density on 2J and the electronic coupling, a series of four substituted triptycene triads (chapter 7) was synthesised. The electron density in the TTC bridging unit was varied by electron donating and electron withdrawing groups in 12,13 position of the TTC bridging unit and thus varying its HOMO/LUMO energy. The last series of two anthracene bridge triads (chapter 8) connected both approaches by restricting the rotation with ortho methyl groups and simultaneously by varying the bridge energies. In order to obtain the electronic properties, steady state absorption and emission spectra of all triads were investigated (chapter 4). Here, all triads show spectral features associated with the separate absorption bands of TAA and the PDI moiety. The reduced QYs, compared to the unsubstituted PDI acceptor, indicate a non radiative quenching mechanism in all triads. The CV data (chapter 5) were used to calculate the energies of possible CSSs and those results were used to assign the CR dynamics into the different Marcus regions. fs TA measurements reveal that all triads form a CSS upon excitation of the PDI moiety. The lifetimes of the involved states and the rate constants were determined by global exponential fits and global target analysis. The CR dynamics upon depopulation of the CSSs were investigated using external magnetic field dependent ns TA spectroscopy. The ns TA maps show that all triads recombine via CRT pathway populating the local 3PDI state in toluene and provided the respective lifetimes. The approximate QYs of triplet formation were determined using actinometry. The magnetic field dependent ns TA data reveal the exchange interaction 2J between singlet and triplet CSS for each triad. Those magnetic field dependent ns TA data in toluene were furthermore treated using a quantum mechanical simulation (done by U.E. Steiner) to extract the rate constants kT and kS for CRT and CRS, respectively. However, the error margins of kS were rather wide. Finally, the electronic couplings between the donor and the acceptor states were obtained by combining the aforementioned experimental results of the rate constants and applying the Bixon Jortner theoretical description of diabatic ET and Andersons perturbative theory of the exchange coupling. Therefore, the experimentally determined values of 2J and the calculated values of kCS and kT were used. The rate constant kS was calculated based on the electronic coupling V1CSS 1S0. The rotationally hindered triads (chapter 6) show a strong influence of the degree of rotational restriction on the lifetimes and rate constants of the CS processes. The rate constants of CS are increasing with increasing rotational freedom. The magnetic field dependent decay data show that the exchange interactions increase with increasing rotational freedom. Based on the CR dynamics, the calculated electronic couplings of the ET processes reflect the same trend along the series. Here, only singlet couplings turned out to be strongly influenced while the triplet couplings are not. Therefore, this series shows that the ET dynamics of donor acceptor systems can strongly be influenced by restricting the rotational freedom. In the substituted triptycene triads (chapter 7), decreasing electron density in the bridging unit causes a decrease of the CS rate constants. The magnetic field dependent decay data show that with decreasing electron density in the bridge the exchange interaction decreases. The CR dynamics-based rate constants and the electronic couplings follow the same trend as the exchange interaction. This series shows that varying the HOMO/LUMO levels of the connecting bridge between donor and acceptor strongly influences the ET processes. In the anthracene bridge triads (chapter 8), the CS process is slow in both triads. The CR was fast in the anthracene triad and is slowed down in the methoxy substituted anthracene bridge triad. The increase of the exchange interaction with increasing electron density in the bridge was more pronounced than in the substituted triptycene triads. Thus, the variation of electron density in the bridge strongly influences the ET processes even though the rotation is restricted. In this thesis, it was shown that the influence of the rotational hindrance as well as the electron density in a connecting bridge have strong influence on all ET processes and the electronic coupling in donor acceptor systems. These approaches can therefore be used to modify magnetic properties of new materials.},
  subject      = {Rotation},
  language  = {en}
}
@phdthesis{deGraafgebButtler2024,
  author    = {de Graaf [geb. Buttler], Simone Linda},
  title     = {From Small to Large Data: Leveraging Synthetic Data for Inventory Management},
  doi       = {10.25972/OPUS-36136},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361364},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In a world of constant change, uncertainty has become a daily challenge for businesses. Rapidly shifting market conditions highlight the need for flexible responses to unforeseen events. Operations Management (OM) is crucial for optimizing business processes, including site planning, production control, and inventory management. Traditionally, companies have relied on theoretical models from microeconomics, game theory, optimization, and simulation. However, advancements in machine learning and mathematical optimization have led to a new research field: data-driven OM. Data-driven OM uses real data, especially time series data, to create more realistic models that better capture decision-making complexities. Despite the promise of this new research area, a significant challenge remains: the availability of extensive historical training data. Synthetic data, which mimics real data, has been used to address this issue in other machine learning applications. Therefore, this dissertation explores how synthetic data can be leveraged to improve decisions for data-driven inventory management, focusing on the single-period newsvendor problem, a classic stochastic optimization problem in inventory management. The first article, "A Meta Analysis of Data-Driven Newsvendor Approaches", presents a standardized evaluation framework for data-driven prescriptive approaches, tested through a numerical study. Findings suggest model performance is not robust, emphasizing the need for a standardized evaluation process. The second article, "Application of Generative Adversarial Networks in Inventory Management", examines using synthetic data generated by Generative Adversarial Networks (GANs) for the newsvendor problem. This study shows GANs can model complex demand relationships, offering a promising alternative to traditional methods. The third article, "Combining Synthetic Data and Transfer Learning for Deep Reinforcement Learning in Inventory Management", proposes a method using Deep Reinforcement Learning (DRL) with synthetic and real data through transfer learning. This approach trains a generative model to learn demand distributions, generates synthetic data, and fine-tunes a DRL agent on a smaller real dataset. This method outperforms traditional approaches in controlled and practical settings, though further research is needed to generalize these findings.},
  subject      = {Bestandsmanagement},
  language  = {en}
}
@phdthesis{Iosip2024,
  author    = {Iosip, Anda-Larisa},
  title     = {Molecular Mechanosensing Mechanisms of the Carnivorous Plant \(Dionaea\) \(muscipula\)},
  doi       = {10.25972/OPUS-28764},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287649},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Plants are able to sense mechanical forces in order to defend themselves against predators, for instance by synthesizing repellent compounds. Very few plants evolved extremely sensitive tactile abilities that allow them to perceive, interpret and respond by rapid movement in the milliseconds range. One such rarity is the charismatic Venus flytrap (Dionaea muscipula) - a carnivorous plant which relies on its spectacular active trapping strategy to catch its prey. The snapping traps are equipped with touch-specialised trigger hairs, that upon bending elicit an action potential (AP). This electrical signal originates within the trigger hairs' mechanosensory cells and further propagates throughout the whole trap, alerting the plant of potential prey. Two APs triggered within thirty seconds will set off the trap and more than five APs will initiate the green stomach formation for prey decomposition and nutrient uptake. Neither the molecular components of the plant's AP nor the Venus flytrap's fast closure mechanism have been fully elucidated yet. Therefore, the general objective of this study is to expound on the molecular basis of touch perception: from AP initiation to trap closure and finally to stomach formation. The typical electrical signal in plants lasts for minutes and its shape is determined by the intensity of the mechanical force applied. In contrast, the Venus flytrap's one-second AP is of all-or-nothing type, similar in shape to the animal AP. In order to gain more insight into the molecular components that give rise to the Venus flytrap's emblematic AP, the transcriptomic landscape of its unique mechanotransducer - the trigger hair - was compared to the rest of the non-specialised tissues and organs. Additionally, the transcriptome of the electrically excitable fully-developed adult trap was compared to non-excitable juvenile traps that are unable to produce sharp APs. Together, the two strategies helped with the identification of electrogenic channels and pumps for each step of the AP as follows: (1) the most specific to the trigger hair was the mechanosensitive channel DmMSL10, making up the best candidate for the initial AP depolarization phase, (2) the K+ outward rectifier DmSKOR could be responsible for repolarisation, (3) further, the proton pump DmAHA4, might kick in during repolarisation and go on with hyperpolarisation and (4) the hyperpolarization- and acid-activated K+ inward rectifier KDM1 might contribute to the re-establishment of electrochemical gradient and the resting potential. Responsible for the AP-associated Ca2+ wave and electrical signal propagation, the glutamate-like receptor DmGLR3.6 was also enriched in the trigger hairs. Together, these findings suggest that the reuse of genes involved in electrical signalling in ordinary plants can give rise to the Venus flytrap's trademark AP. The Venus flytrap has been cultivated ever since its discovery, generating more than one hundred cultivars over the years. Among them, indistinguishable from a normal Venus flytrap at first sight, the 'ERROR' cultivar exhibits a peculiar behaviour: it is unable to snap its traps upon two APs. Nevertheless, it is still able to elicit normal APs. To get a better understanding of the key molecular mechanisms and pathways that are essential for a successful trap closure, the 'ERROR' mutant was compared to the functional wild type. Timelapse photography led to the observation that the 'ERROR' mutants were able to leisurely half close their traps when repeated mechanostimulation was applied (10 minutes after 20 APs, 0.03 Hz). As a result of touch or wounding in non-carnivorous plants, jasmonic acid (JA) is synthesized, alerting the plants of potential predators. Curiously, the JA levels were reduced upon mechanostimulation and completely impaired upon wounding in the 'ERROR' mutant. In search of genes accountable for the 'ERROR' mutant's defects, the transcriptomes of the two phenotypes were compared before and after mechanostimulation (1h after 10 APs, 0.01 Hz). The overall dampened response of the mutant compared to the wild type, was reflected at transcriptomic level as well. Only about 50\% of wild type's upregulated genes after touch stimulation were differentially expressed in 'ERROR' and they manifested only half of the wild type's expression amplitude. Among unresponsive functional categories of genes in 'ERROR' phenotype, there were: cell wall integrity surveilling system, auxin biosynthesis and stress-related transcription factors from the ethylene-responsive AP2/ERF and C2H2-ZF families. Deregulated Ca2+-decoding as well as redox-related elements together with JA-pathway components might also contribute to the malfunctioning of the 'ERROR' mutant. As the mutant does not undergo full stomach formation after mechanical treatment, these missing processes represent key milestones that might mediate growth-defence trade-offs under JA signalling. This confirms the idea that carnivory has evolved by recycling the already available molecular machineries of the ubiquitous plant immune system. To better understand the mutant's defect in the trap snapping mechanism, the ground states (unstimulated traps) of the two phenotypes were compared. In this case, many cell wall-related genes (e.g. expansins) were downregulated in the 'ERROR' mutant. For the first time, these data point to the importance of a special cell wall architecture of the trap, that might confer the mechanical properties needed for a functional buckling system - which amplifies the speed of the trap closure. This study provides candidate channels for each of the AP phases that give rise to and shape the sharp Venus flytrap-specific AP. It further underlines the possible contribution of the cell wall architecture to the metastable ready-to-snap configuration of the trap before stimulation - which might be crucial for the buckling-dependent snapping. And finally, it highlights molecular milestones linked to defence responses that ensure trap morphing into a green stomach after mechanostimulation. Altogether, these processes prove to be interdependent and essential for a successful carnivorous lifestyle.},
  subject      = {Venusfliegenfalle},
  language  = {en}
}
@phdthesis{Reissland2024,
  author    = {Reissland, Michaela},
  title     = {USP10 is a \(de\) \(novo\) tumour-specific regulator of β-Catenin and contributes to cancer stem cell maintenance and tumour progression},
  doi       = {10.25972/OPUS-31957},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319579},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Colorectal Cancer (CRC) is the third most common cancer in the US. The majority of CRC cases are due to deregulated WNT-signalling pathway. These alterations are mainly caused by mutations in the tumour suppressor gene APC or in CTNNB1, encoding the key effector protein of this pathway, β-Catenin. In canonical WNT-signalling, β-Catenin activates the transcription of several target genes, encoding for proteins involved in proliferation, such as MYC, JUN and NOTCH. Being such a critical regulator of these proto-oncogenes, the stability of β-Catenin is tightly regulated by the Ubiquitin-Proteasome System. Several E3 ligases that ubiquitylate and degrade β-Catenin have been described in the past, but the antagonists, the deubiquitylases, are still unknown. By performing an unbiased siRNA screen, the deubiquitylase USP10 was identified as a de novo positive regulator of β-Catenin stability in CRC derived cells. USP10 has previously been shown in the literature to regulate both mutant and wild type TP53 stability, to deubiquitylate NOTCH1 in endothelial cells and to be involved in the regulation of AMPKα signalling. Overall, however, its role in colorectal tumorigenesis remains controversial. By analysing publicly available protein and gene expression data from colorectal cancer patients, we have shown that USP10 is strongly upregulated or amplified upon transformation and that its expression correlates positively with CTNNB1 expression. In contrast, basal USP10 levels were found in non-transformed tissues, but surprisingly USP10 is upregulated in intestinal stem cells. Endogenous interaction studies in CRC-derived cell lines, with different extend of APCtruncation, revealed an APC-dependent mode of action for both proteins. Furthermore, by utilising CRISPR/Cas9, shRNA-mediated knock-down and overexpression of USP10, we could demonstrate a regulation of β-Catenin stability by USP10 in CRC cell lines. It is widely excepted that 2D cell culture systems do not reflect complexity, architecture and heterogeneity and are therefore not suitable to answer complex biological questions. To overcome this, we established the isolation, cultivation and genetically modification of murine intestinal organoids and utilised this system to study Usp10s role ex vivo. By performing RNA sequencing, dependent on different Usp10 levels, we were able to recapitulate the previous findings and demonstrated Usp10 as important regulator of β-dependent regulation of stem cell homeostasis. Since genetic depletion of USP10 resulted in down-regulation of β-Catenin-dependent transcription, therapeutic intervention of USP10 in colorectal cancer was also investigated. Commercial and newly developed inhibitors were tested for their efficacy against USP10, but failed to significantly inhibit USP10 activity in colorectal cancer cells. To validate the findings from this work also in vivo, development of a novel mouse model for colorectal cancer has begun. By combining CRISPR/Cas9 and classical genetic engineering with viral injection strategies, WT and genetically modified mice could be transformed and, at least in some animals, intestinal lesions were detectable at the microscopic level. The inhibition of USP10, which we could describe as a de novo tumour-specific regulator of β-Catenin, could become a new therapeutic strategy for colorectal cancer patients.},
  subject      = {Biomedizin},
  language  = {en}
}
@phdthesis{Wussmann2024,
  author    = {Wußmann, Maximiliane},
  title     = {Humane organotypische 3D Modelle des Malignen Melanoms als in vitro Testsystem f{\"u}r die Bewertung der Wirksamkeit von anti-Tumor Therapeutika},
  doi       = {10.25972/OPUS-36100},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361005},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Das maligne Melanom, eine der seltensten, aber gleichzeitig auch die t{\"o}dlichste dermatologische Malignit{\"a}t, gekennzeichnet durch die Neigung zu einer fr{\"u}hen Metastasierung sowie die rasche Entwicklung von Therapieresistenzen, z{\"a}hlt zu den Tumorentit{\"a}ten mit dem h{\"o}chsten Anstieg der Inzidenz weltweit. Mausmodelle werden h{\"a}ufig verwendet, um die Melanomagenese zu erforschen und neue effektive therapeutische Strategien zu entwickeln, spiegeln die menschliche Physiologie allerdings nur unzureichend wider. In zweidimensionalen (2D) Zellkulturen mangelt es dagegen an wichtigen Komponenten der Mikroumgebung des Tumors und dem dreidimensionalen Gewebekontext. Um dieses Manko zu beheben und die Entwicklung von auf den Menschen {\"u}bertragbaren Tumormodellen in der onkologischen Forschung voranzutreiben, wurde als Alternative zu Zellkulturen und Tierversuchen humane organotypische dreidimensionale (3D) Melanom-Modelle als in vitro Testsystem f{\"u}r die Bewertung der Wirksamkeit von anti-Tumor Therapeutika entwickelt. Im Zuge dieser Arbeit konnte das in vitro Melanom-Modell entscheidend weiterentwickelt werden. So konnten Modelle unterschiedlichster Komplexit{\"a}t etabliert werden, wobei abh{\"a}ngig von der Fragestellung einfachere epidermale bis hin zu unterschiedlich komplexen Vollhautmodellen Anwendung finden. Durch Simulation der Tumor-Mikroumgebung eignen sich diese zur pr{\"a}klinischen Validierung neuer Tumor-Therapeutika, sowie der Erforschung pathologischer Vorg{\"a}nge, von der Tumor-Formierung bis zur Metastasierung. Zudem konnten erfolgreich unterschiedlichste humane Melanomzelllinien ins Modell integriert werden; dadurch, dass sich diese durch ihre Treibermutationen, die zur Krankheitsentstehung beitragen, unterscheiden, stellen sie unterschiedliche Anspr{\"u}che an potentielle therapeutische Angriffspunkte und erm{\"o}glichen das Widerspiegeln vieler Melanom-Subtypen im Modell. Ferner ist es m{\"o}glich, verschiedene Stadien der Tumor-Entwicklung {\"u}ber die Zugabe von Melanomzellen in Einzelsuspension bzw. von Melanom-Sph{\"a}roiden widerzuspiegeln. Es konnte f{\"u}r bestimmte Therapie-Ans{\"a}tze, wie zielgerichtete Therapien, z.B. die Gabe von sich in der Klinik im Einsatz befindlicher BRAF-/MEK-Inhibitoren, gezeigt werden, dass sich die etablierten Modelle hervorragend als pr{\"a}klinische Testsysteme zur Wirksamkeitsbewertung eignen. Zudem bieten sich einzigartige M{\"o}glichkeiten, um die Interaktion humaner Tumorzellen und gesunder Zellen in einem Gewebeverband zu untersuchen. Ferner konnten drei neue technische Analyse-Verfahren zur nicht-invasiven Detektion der Tumor- Pro- und Regression, Beurteilung der Wirksamkeit von potenziellen Anti-Tumor-Therapien sowie der Evaluierung des Tumor-Metabolismusses implementiert werden. Perspektivisch erm{\"o}glichen immun-kompetente Melanom-Modelle die Austestung neuer Immun- und Zelltherapien in einem voll humanen System; gleichzeitig leisten die etablierten Modelle einen signifikanten Beitrag zur Reduktion von Tierexperimenten.},
  subject      = {Melanom},
  language  = {de}
}
@phdthesis{Schaefer2024,
  author    = {Schaefer, Bastian},
  title     = {Eigenschaften von synthetischen Bandersatzmaterialien zum MPFL-Ersatz - biomechanische in vitro Studie am porcinen Modell},
  doi       = {10.25972/OPUS-36139},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361396},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Der MPFL-Ersatz ist ein g{\"a}ngiges Therapieverfahren zur Behandlung einer patellofemoralen Instabilit{\"a}t. Die Operationstechniken unterscheiden sich zumeist an der patellaren Fixationsmethode und der Auswahl der Transplantate. Biomechanische Studien, welche sich mit den Eigenschaften implantatfreier oss{\"a}rer Fixationsmethoden beim MPFL-Ersatz unter Verwendung k{\"u}nstlicher Transplantate besch{\"a}ftigen gibt es nach aktueller Recherche nicht. Ziel dieser Arbeit war es, die biomechanischen Eigenschaften zweier patellarer Bohrkanalfixationstechniken beim MPFL-Ersatz mit unterschiedlichem k{\"u}nstlichen Bandersatzmaterial zu ermitteln. Die Hypothese war, dass die biomechanischen Eigenschaften in Elongation, Steifigkeit, Prim{\"a}rstabilit{\"a}t und maximaler Ausreißkraft mit denen der bereits etablierten Verfahren und dem nativen MPFL vergleichbar sind. Hierzu wurden 80 porcine Kniescheiben randomisiert in 8 Gruppen aufgeteilt und getestet. In den Gruppen 1-4 wurden parallele, transpatellare Bohrkan{\"a}le mit Tapes der Breiten 2 mm, 3 mm, 4 mm und 5 mm getestet. In den Gruppen 5-8 wurden V-Kanal-Fixationsmethoden mit B{\"a}ndern der Breite von 2 mm, 3 mm, 4 mm und 5 mm untersucht. Zus{\"a}tzlich wurden die biomechanischen Grundeigenschaften der nativen Tapes ermittelt. Alle Tests durchliefen jeweils drei Messabschnitte. Hierbei fand zun{\"a}chst eine Pr{\"a}konditionierung mit 10 Zyklen zwischen 5 N und 20 N statt. Daraufhin folgte eine zyklische Belastung mit 1000 Zyklen zwischen 5 N und 50 N. Am Ende wurde eine maximale Kraftapplikation bis zum Versagen der Fixationskomplexe durchgef{\"u}hrt. Im Rahmen der Messungen wurden Elongation, Steifigkeit, Yield Load und Maximum Load bestimmt. Es konnten Unterschiede zwischen den beiden Fixationsmethoden und den verwendeten Tapes festgestellt werden. Alle acht Gruppen zeigten eine h{\"o}here Prim{\"a}rstabilit{\"a}t als das humane MPFL. Bezogen auf die biomechanischen Eigenschaften und den Versagensmechanismus konnte in dieser Studie ein Vorteil der parallelen transpatellaren Bohrkan{\"a}le gegen{\"u}ber den V- Kanaltechniken festgestellt werden. Die Werte mit der h{\"o}chsten maximalen Ausreißkraft wurden in Gruppe 3 (631,6 ± 83,1 N) und Gruppe 1 (592,9 ± 170,1 N) gemessen. Diese zeigten eine h{\"o}here Prim{\"a}rstabilit{\"a}t mit geringerer Elongation und Steifigkeit im Vergleich zu den in der aktuellen Literatur beschriebenen biomechanischen Studien, welche sich mit unterschiedlichen und teilweise bereits etablierten MPFL-Ersatzverfahren besch{\"a}ftigten. Eine implantatfreie MPFL-Rekonstruktion mit transpatellaren parallelen Bohrkan{\"a}len unter Verwendung eines 2 mm Fiber Tapes (Fa. Arthrex) oder eines 4 mm Tapes (Fa. Topester) k{\"o}nnten dementsprechend eine gute Alternative zur operativen Therapie einer patellofemoralen Instabilit{\"a}t sein.},
  subject      = {Patellaluxation},
  language  = {de}
}
@phdthesis{Kagerer2024,
  author    = {Kagerer, Philipp Thomas},
  title     = {Two-Dimensional Ferromagnetism and Topology at the Surface of MnBi\(_2\)Te\(_4\) - Bi\(_2\)Te\(_3\) Heterostructures - MBE Growth, Magnetism and Electronic Properties},
  doi       = {10.25972/OPUS-36012},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360121},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In this thesis, a model system of a magnetic topological heterostructure is studied, namely a heterosystem consisting of a single ferromagnetic septuple-layer (SL) of \(MnBi_2Te_4\) on the surface of the three-dimensional topological insulator \(Bi_2Te_3\). Using MBE and developing a specialized experimental setup, the first part of this thesis deals with the growth of \(Bi_2Te_3\) and thin films of \(MnBi_2Te_4\) on \(BaF_2\)-substrates by the co-evaporation of its binary constituents. The structural analysis is conducted along several suitable probes such as X-ray diffraction (XRD, XRR), AFM and scanning tunnelling electron microscopy (STEM). It is furthermore found that the growth of a single septuple-layer of \(MnBi_2Te_4\) on the surface of \(Bi_2Te_3\) can be facilitated. By using X-ray absorption and circular magnetic dichroism (XAS, XMCD), the magnetic properties of \(MnBi_2Te_4\) are explored down to the monolayer limit. The layered nature of the vdW crystal and a strong uniaxial magnetocrystalline anisotropy establish stable out-of plane magnetic order at the surface of \(MnBi_2Te_4\), which is stable even down to the 2D limit. Pushing the material system to there, i.e. a single SL \(MnBi_2Te_4\) further allows to study the phase transition of this 2D ferromagnet and extract its critical behaviour with \(T_c \, = \, 14.89~k\) and \(\beta \, = \, 0.484\). Utilizing bulk crystals of the ferromagnetic \(Fe_3GeTe_2\) as substrate allows to influence, enhance and bias the magnetism in the single SL of \(MnBi_2Te_4\). By growing heterostructures of the type \(MnBi_2Te_4\) -- n layer \(Bi_2Te_3\) -- \(Fe_3GeTe_2\)for n between 0 and 2, it is shown, that a considerable magnetic coupling can be introduced between the \(MnBi_2Te_4\) top-layer and the substrate. Finally the interplay between topology and magnetism in the ferromagnetic extension is studied directly by angle-resolved photoemission spectroscopy. The heterostructure is found to host a linearly dispersing TSS at the centre of the Brillouin zone. Using low temperature and high-resolution ARPES a large magnetic gap opening of \(\sim\) 35 meV is found at the Dirac point of the TSS. By following its temperature evolution, it is apparent that the scaling behaviour coincides with the magnetic order parameter of the modified surface.},
  subject      = {Molekularstrahlepitaxie},
  language  = {en}
}
@phdthesis{Gaballa2024,
  author    = {Gaballa, Abdallah Hatem Hassan Hosny Ahmed},
  title     = {PAF1c drives MYC-mediated immune evasion in pancreatic ductal adenocarcinoma},
  doi       = {10.25972/OPUS-36045},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360459},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The expression of the MYC proto-oncogene is elevated in a large proportion of patients with pancreatic ductal adenocarcinoma (PDAC). Previous findings in PDAC have shown that this increased MYC expression mediates immune evasion and promotes S-phase progression. How these functions are mediated and whether a downstream factor of MYC mediates these functions has remained elusive. Recent studies identifying the MYC interactome revealed a complex network of interaction partners, highlighting the need to identify the oncogenic pathway of MYC in an unbiased manner. In this work, we have shown that MYC ensures genomic stability during S-phase and prevents transcription-replication conflicts. Depletion of MYC and inhibition of ATR kinase showed a synergistic effect to induce DNA damage. A targeted siRNA screen targeting downstream factors of MYC revealed that PAF1c is required for DNA repair and S-phase progression. Recruitment of PAF1c to RNAPII was shown to be MYC dependent. PAF1c was shown to be largely dispensable for cell proliferation and regulation of MYC target genes. Depletion of CTR9, a subunit of PAF1c, caused strong tumor regression in a pancreatic ductal adenocarcinoma model, with long-term survival in a subset of mice. This effect was not due to induction of DNA damage, but to restoration of tumor immune surveillance. Depletion of PAF1c resulted in the release of RNAPII with transcription elongation factors, including SPT6, from the bodies of long genes, promoting full-length transcription of short genes. This resulted in the downregulation of long DNA repair genes and the concomitant upregulation of short genes, including MHC class I genes. These data demonstrate that a balance between long and short gene transcription is essential for tumor progression and that interference with PAF1c levels shifts this balance toward a tumor-suppressive transcriptional program. It also directly links MYC-mediated S-phase progression to immune evasion. Unlike MYC, PAF1c has a stable, known folded structure; therefore, the development of a small molecule targeting PAF1c may disrupt the immune evasive function of MYC while sparing its physiological functions in cellular growth.},
  subject      = {Myc},
  language  = {en}
}
@phdthesis{vonderHeide2024,
  author    = {von der Heide, Julia Magdalena},
  title     = {Ist eine Berechnung der Geometrie der Halswirbelk{\"o}rper anhand ihrer Morphologie im Kindesalter und somit eine Individualisierung der CVM-Methode m{\"o}glich?},
  doi       = {10.25972/OPUS-36075},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360753},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Ziel der vorliegenden Studie war es zu untersuchen, ob anhand geometrischer Merkmale der HWK im Kindesalter eine sichere individuelle Vorhersage der Morphologie der HWK zum Ende der Entwicklung m{\"o}glich ist. Hierdurch k{\"o}nnte eine Individualisierung der CVM-Methode und somit eine Einsch{\"a}tzung des bereits verstrichenen Wachstums erfolgen. Zu diesem Zweck wurden insgesamt 1377 FRS-Aufnahmen von 267 Patienten - 110 weibliche und 157 m{\"a}nnliche - aus dem Archiv der Poliklinik f{\"u}r Kieferorthop{\"a}die des Universit{\"a}tsklinikums W{\"u}rzburg digitalisiert und untersucht. Die HWK wurden im Programm OnyxCeph (Herst.: Image Instruments GmbH) quantifiziert und die berechneten Werte mit der Software SPSS statistisch ausgewertet. Mittels linearer Regressionen wurde versucht, anhand der Morphologie der Wirbelk{\"o}rper vor dem puberalen Wachstumsschub auf die Geometrie der HWK im Erwachsenenalter zu schließen. Zur Illustrierung wurden Streudiagramm und die dazugeh{\"o}rigen Abfolgen von R{\"o}ntgenbildern dargestellt. Eine Sch{\"a}tzung der Geometrie der HWK im Erwachsenenalter w{\"u}rde bei den separat betrachteten Parametern und bei einer gemeinsamen Betrachtung der Parameter kaum zu korrekten Einsch{\"a}tzungen f{\"u}hren. Die Streudiagramme mit den Bilderabfolgen st{\"u}tzen diese These ebenfalls und illustrieren die m{\"o}gliche Fehleinsch{\"a}tzung der Geometrie. Die Ergebnisse der Studie zeigen erneut, dass die Geometrie der HWK im Erwachsenenalter sehr variabel ist, wie komplex die Entwicklung der HWK ist und dass anhand ihrer Geometrie im Kindesalter keine sichere Einsch{\"a}tzung der skelettalen Reife m{\"o}glich ist. Eine Individualisierung der CVM-Methode ist anhand der in dieser Studie untersuchten Parameter nicht m{\"o}glich. Somit l{\"a}sst sich schlussfolgern, dass die CVM-Methode nicht als alleinige Methode zur pr{\"a}zisen skelettalen Alterseinsch{\"a}tzung verl{\"a}sslich genutzt werden kann, sondern f{\"u}r eine sichere Beurteilung weitere Reifeindikatoren hinzugezogen werden sollten. Allerdings sollten hierzu zus{\"a}tzliche radiologische Untersuchungen, wie beispielsweise die Handr{\"o}ntgenaufnahme, nur dann durchgef{\"u}hrt werden, wenn diese dem ALARA-Prinzip entsprechen.},
  subject      = {Skelett},
  language  = {de}
}
@phdthesis{Glueck2024,
  author    = {Gl{\"u}ck, Valentina},
  title     = {Habitual avoidance in trait anxiety and anxiety disorders},
  doi       = {10.25972/OPUS-36022},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360227},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Maladaptive avoidance behaviors can contribute to the maintenance of fear, anxiety, and anxiety disorders. It has been proposed that, throughout anxiety disorder progression, extensively repeated avoidance may become a habit (i.e., habitual avoidance) instead of being controlled by internal threat-related goals (i.e., goal-directed avoidance). However, the process of the acquisition of habitual avoidance in anxiety disorders is not yet well understood. Accordingly, the current thesis aimed to investigate experimentally whether trait anxiety and anxiety disorders are associated with an increased shift from goal-directed to habitual avoidance. The aim of Study 1 was to develop an experimental operationalization of maladaptive habitual avoidance. To this end, we adapted a commonly used action control task, the outcome devaluation paradigm. In this task, habitual avoidance was operationalized as persistent responses after extensive training to avoid an unpleasant stimulus when the aversive outcome was devalued, i.e., when individuals knew the aversive outcome could not occur anymore. We included indicators for costly and low-cost habitual avoidance, whereby habitual avoidance was associated with a monetary cost, while low-cost habitual avoidance was not associated with monetary costs. In Experiment 1 of Study 1, a pronounced costly and non-costly outcome devaluation effect was observed. However, this result may have partly resulted from trial-and-error learning or a better-safe-than-sorry strategy since not instructions about the stimulus-response-outcome contingencies after the outcome devaluation procedure had been provided to the participants. In Experiment 2 of Study 1, instructions on these stimulus-response-outcome contingencies were included to prevent the potential confounders. As a result, we observed no indicators for costly habitual avoidance, but evidence for low-cost habitual avoidance, potentially because competing goal-directed responses could easily be implemented and inhibited costly habitual avoidance tendencies. In Study 2, the strength of habitual avoidance acquisition was compared between participants with and without anxiety disorders, using the experimental task of Experiment 1 in Study 1. The results indicated that costly and low-cost habitual avoidance was not more pronounced in participants with anxiety disorders than in the healthy control group. However, in an exploratory subgroup comparison, panic disorder predicted more substantial habitual avoidance acquisition than social anxiety disorder. In Study 3, we investigated whether trait anxiety as a risk factor for anxiety disorders is associated with a specific increased shift from goal-directed to habitual avoidance and approach. The task from the Experiment 1 of Study 1 was adapted to include parallel versions for operationalizing habitual avoidance and habitual approach responses. Using a within-subjects design, the individuals - pre-screened for high and low trait anxiety - took part in the approach and the avoidance outcome devaluation task version. The results suggested stronger non-costly habitual responses in more highly trait-anxious individuals independent of the task version, and suggested a tendency towards an impact of trait anxiety on costly habitual approach rather than on costly habitual avoidance. In summary, individuals with high trait anxiety or anxiety disorders did not develop habitual avoidance more readily than individuals with low trait anxiety or without anxiety disorders. Therefore, this thesis does not support the assumption that an increased tendency to acquire habitual avoidance contributes to persistent maladaptive avoidance in anxiety disorders. The thesis also contributes to the discourse on the validity of outcome devaluation studies in general by highlighting the impact of task features, such as the instructions after the outcome devaluation procedure or the task difficulty in the test phase, on the experimental results. Such validity issues may partly explain the heterogeneity of findings in research with the outcome devaluation paradigm. We suggest ways towards more valid operationalizations of habitual avoidance in future studies.},
  subject      = {Gewohnheit},
  language  = {en}
}
@phdthesis{Machwart2024,
  author    = {Machwart, Khaled},
  title     = {Modulatorischer Einfluss von Levosimendan bei dem Isch{\"a}mie-Reperfusionsschaden auf die myokardiale Mitochondrienfunktion},
  doi       = {10.25972/OPUS-36102},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361021},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die vorliegende Studie untersuchte den Effekt von Levosimendan auf die mitochondriale Funktionen im Herzmuskel, insbesondere im Zusammenhang mit dem Isch{\"a}mie/Reperfusions-Schaden. Methoden: In der Studie wurde ein retrogrades Langendorff-Modell verwendet, um die Auswirkungen von Levosimendan, dem Isch{\"a}mie/Reperfusions-Schaden sowie deren Kombination auf die mitochondrialen Funktionen im Herzmuskel zu untersuchen. Dazu wurden vier verschiedene Gruppen von Rattenherzen entsprechend den experimentellen Bedingungen perfundiert, und ihre Funktionen wurden analysiert. Ergebnisse: Der Isch{\"a}mie/Reperfusions-Schaden beeintr{\"a}chtigte die myokardiale Ventrikelfunktion. Zus{\"a}tzlich wurde eine Hypopolarisation des mithochondrialen Membranpotentials in den mit Levosimendan oder Isch{\"a}mie behandelten Gruppen festgestellt. Die ATP-Synthese in den Gruppen mit Levosimendan und Isch{\"a}mie war reduziert. Schlussfolgerung: Levosimendan zeigt signifikante Einfl{\"u}sse auf die Atmungsfunktion der mitochondrialen Komplexe IV und V sowie auf das Membranpotential. Diese Ph{\"a}nomene k{\"o}nnten einem mito-K+ ATP-abh{\"a}ngigen Mechanismus zugrunde liegen. Obwohl Levosimendan w{\"a}hrend des Isch{\"a}mie/Reperfusionsschadens eine protektive Wirkung hinsichtlich einer Ca2+- {\"U}berlastung aufweist, bleibt der kumulative Einfluss der beeintr{\"a}chtigten ATP-Generierung auf die gesamte Myokardfunktion zu kl{\"a}ren.},
  subject      = {Isch{\"a}mie},
  language  = {de}
}
@phdthesis{Amini2024,
  author    = {Amini, Emad},
  title     = {How central and peripheral clocks and the neuroendocrine system interact to time eclosion behavior in \(Drosophila\) \(melanogaster\)},
  doi       = {10.25972/OPUS-36130},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361309},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {To grow larger, insects must shed their old rigid exoskeleton and replace it with a new one. This process is called molting and the motor behavior that sheds the old cuticle is called ecdysis. Holometabolic insects have pupal stages in between their larval and adult forms, during which they perform metamorphosis. The pupal stage ends with eclosion, i.e., the emergence of the adult from the pupal shell. Insects typically eclose at a specific time during the day, likely when abiotic conditions are at their optimum. A newly eclosed insect is fragile and needs time to harden its exoskeleton. Hence, eclosion is regulated by sophisticated developmental and circadian timing mechanisms. In Drosophila melanogaster, eclosion is limited to a daily time window in the morning, regarded as the "eclosion gate". In a population of laboratory flies entrained by light/dark cycles, most of the flies eclose around lights on. This rhythmic eclosion pattern is controlled by the circadian clock and persists even under constant conditions. Developmental timing is under the control of complex hormonal signaling, including the steroid ecdysone, insulin-like peptides, and prothoracicotropic hormone (PTTH). The interactions of the central circadian clock in the brain and a peripheral clock in the prothoracic gland (PG) that produces ecdysone are important for the circadian timing of eclosion. These two clocks are connected by a bilateral pair of peptidergic PTTH neurons (PTTHn) that project to the PG. Before each molt, the ecdysone level rises and then falls shortly before ecdysis. The falling ecdysone level must fall below a certain threshold value for the eclosion gate to open. The activity of PTTHn is inhibited by short neuropeptide F (sNPF) from the small ventrolateral neurons (sLNvs) and inhibition is thought to lead to a decrease in ecdysone production. The general aim of this thesis is to further the understanding of how the circadian clock and neuroendocrinal pathways are coordinated to drive eclosion rhythmicity and to identify when these endocrinal signaling pathways are active. In Chapter I, a series of conditional PTTHn silencing-based behavioral assays, combined with neuronal activity imaging techniques such as non-invasive ARG-Luc show that PTTH signaling is active and required shortly before eclosion and may serve to phase-adjust the activity of the PG at the end of pupal development. Trans-synaptic anatomical stainings identified the sLNvs, dorsal neurons 1 (DN1), dorsal neurons 2 (DN2), and lateral posterior neurons (LPNs) clock neurons as directly upstream of the PTTHn. Eclosion motor behavior is initiated by Ecdysis triggering hormone (ETH) which activates a pair of ventromedial (Vm) neurons to release eclosion hormone (EH) which positively feeds back to the source of ETH, the endocrine Inka cells. In Chapter II trans-synaptic tracing showed that most clock neurons provide input to the Vm and non-canonical EH neurons. Hence, clock can potentially influence the ETH/EH feedback loop. The activity profile of the Inka cells and Vm neurons before eclosion is described. Vm and Inka cells are active around seven hours before eclosion. Interestingly, all EH neurons appear to be exclusively peptidergic. In Chapter III, using chemoconnectomics, PTTHns were found to express receptors for sNPF, allatostatin A (AstA), allatostatin C (AstC), and myosuppressin (Ms), while EH neurons expressed only Ms and AstA receptors. Eclosion assays of flies with impaired AstA, AstC, or Ms signaling do not show arrhythmicity under constant conditions. However, optogenetic activation of the AstA neurons strongly suppresses eclosion. Chapter IV focuses on peripheral ventral' Tracheal dendrite (v'Td) and class IV dendritic arborization (C4da) neurons. The C4da neurons mediate larval light avoidance through endocrine PTTH signaling. The v'Td neurons mainly receive O2/CO2 input from the trachea and are upstream of Vm neurons but are not required for eclosion rhythmicity. Conditional ablation of the C4da neurons or torso (receptor of PTTH) knock-out in the C4da neurons impaired eclosion rhythmicity. Six to seven hours before eclosion, PTTHn, C4da, and Vm neurons are active based on ARG-Luc imaging. Thus, C4da neurons may indirectly connect the PTTHn to the Vm neurons. In summary, this thesis advances our knowledge of the temporal activity and role of PTTH signaling during pupal development and rhythmic eclosion. It further provides a comprehensive characterization of the synaptic and peptidergic inputs from clock neurons to PTTHn and EH neurons. AstA, AstC, and Ms are identified as potential modulators of eclosion circuits and suggest an indirect effect of PTTH signaling on EH signaling via the peripheral sensory C4da neurons.},
  subject      = {Neuroendokrines System},
  language  = {en}
}
@phdthesis{CruzdeCasas2024,
  author    = {Cruz de Casas, Paulina},
  title     = {Sphingolipids as modulators of T cell function},
  doi       = {10.25972/OPUS-35969},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359698},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The immune system is responsible for the preservation of homeostasis whenever a given organism is exposed to distinct kinds of perturbations. Given the complexity of certain organisms like mammals, and the diverse types of challenges that they encounter (e.g. infection or disease), the immune system evolved to harbor a great variety of distinct immune cell populations with specialized functions. For instance, the family of T cells is sub-divided into conventional (Tconv) and unconventional T cells (UTCs). Tconv form part of the adaptive arm of the immune system and are comprised of αβ CD4+ or CD8+ cells that differentiate from na{\"i}ve to effector and memory populations upon activation and are essential during infection and cancer. Furthermore, UTCs, which include γδ T cells, NKT and MAIT, are involved in innate and adaptive immune responses, due to their dual mode of activation, through cytokines (innate-like) or TCR (adaptive), and function. Despite our understanding of the basic functions of T cells in several contexts, a great number of open questions related to their basic biology remain. For instance, the mechanism behind the differentiation of na{\"i}ve CD4+ and CD8+ T cells into effector and memory populations is not fully understood. Moreover, the exact function and relevance of distinct UTC subpopulations in a physiological context have not been fully clarified. Here, we investigated the factors mediating na{\"i}ve CD8+ T cell differentiation into effector and memory cells. By using flow cytometry, mass spectrometry, enzymatic assays, and transgenic mouse models, we found that the membrane bound enzyme sphingomyelin-phosphodiesterase acid-like 3b (Smpdl3b) is crucial for the maintenance of memory CD8+ T cells. Our data show that the absence of Smpdl3b leads to diminished CD8+ T cell memory, and a loss of stem-like memory populations due to an aggravated contraction. Our scRNA-seq data suggest that Smpdl3b could be involved in clathrinmediated endocytosis through modulation of Huntingtin interacting protein 1 (Hip1) levels, likely regulating TCR-independent signaling events. Furthermore, in this study we explored the role of UTCs in lymph node-specific immune responses. By using transgenic mouse models for photolabeling, lymph node transplantation models, infection models and flow cytometry, we demonstrate that S1P regulates the migration of tissue-derived UTC from tissues to draining lymph nodes, resulting in heterogeneous immune responses mounted by lymph nodes draining different tissues. Moreover, our unbiased scRNAseq and single lineage-deficient mouse models analysis revealed that all UTC lineages (γδ T cells, NKT and MAIT) are organized in functional units, based on transcriptional homogeneity, shared microanatomical location and migratory behavior, and numerical and functional redundancy. Taken together, our studies describe additional cell intrinsic (Smpdl3b) and extrinsic (S1Pmediated migration) functions of sphingolipid metabolism modulating T cell biology. We propose the S1P/S1PR1/5 signaling axis as the potential survival pathway for Smpdl3b+ memory CD8+ T cells and UTCs, mainly in lymph nodes. Possibly, Smpdl3b regulates S1P/S1PR signaling by balancing ligandreceptor endocytosis, while UTCs migrate to lymph nodes during homeostasis to be exposed to specific levels of S1P that assure their maintenance. Our results are clinically relevant, since several drugs modulating the S1P/S1PR signaling axis or the levels of Smpdl3b are currently used to treat human diseases, such as multiple sclerosis and B cell-mediated diseases. We hope that our discoveries will inspire future studies focusing on sphingolipid metabolism in immune cell biology.},
  subject      = {T-Lymphozyt},
  language  = {en}
}
@phdthesis{Gabel2024,
  author    = {Gabel, Martin Sebastian},
  title     = {Behavioural resistance to \(Varroa\) \(destructor\) in the Western honeybee \(Apis\) \(mellifera\) - Mechanisms leading to decreased mite reproduction},
  doi       = {10.25972/OPUS-36053},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360536},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The Western Honeybee (Apis mellifera) is among the most versatile species in the world. Its adaptability is rooted in thousands of the differently specialized individuals acting jointly together. Thus, bees that are able to handle a certain task or condition well can back up other individuals less capable to do so on the colony level. Vice versa, the latter individuals might perform better in other situations. This evolutionary recipe for success ensures the survival of colonies despite challenging habitat conditions. In this context, the ectoparasitic mite Varroa destructor reflects the most pronounced biotic challenge to honeybees worldwide. Without proper treatment, infested colonies rapidly dwindle and ultimately die. Nevertheless, resistance behaviours against this parasite have evolved in some populations through natural selection, enabling colonies to survive untreated. In this, different behaviours appear to be adapted to the respective habitat conditions and may complement each other. Yet, the why and how of this behavioural response to the mite remains largely unknown. My thesis focuses on the biological background of Varroa-resistance traits in honeybees and presents important findings for the comprehension of this complex host-parasite interaction. Based on this, I draw implications for both, applied bee breeding and scientific investigations in the field of Varroa-resistance. Specifically, I focus on two traits commonly found in resistant and, to a lower degree, also mite-susceptible colonies: decreased mite reproduction and the uncapping and subsequent recapping of sealed brood cells. Examining failures in the reproductive success of mites as a primary mechanism of Varroa-resistance, I was able to link them to specific bee behaviours and external factors. Since mite reproduction and the brood rearing of bees are inevitably connected, I first investigated the effects of brood interruption on the reproductive success of mites. Brood interruption decreased the reproductive success of mites both immediately and in the long term. By examining the causes of reproductive failure, I could show that this was mainly due to an increased share of infertile mites. Furthermore, I proved that interruption in brood rearing significantly increased the expression of recapping behaviour. These findings consequently showed a dynamic modulation of mite reproduction and recapping, as well as a direct effect of brood interruption on both traits. To further elucidate the plasticity in the expression of both traits, I studied mite reproduction, recapping behaviour and infestation levels over the course of three years. The resulting extensive dataset unveiled a significant seasonal variation in mite reproduction and recapping. In addition, I show that recapping decreases the reproductive success of mites by increasing delayed developing female offspring and cells lacking male offspring. By establishing a novel picture-based brood investigation method, I could furthermore show that both the removal of brood cells and recapping activity specifically target brood ages in which mite offspring would be expected. Recapping, however, did not cause infertility of mites. Considering the findings of my first study, this points towards complementary mechanisms. This underlines the importance of increased recapping behaviour and decreased mite reproduction as resistance traits, while at the same time emphasising the challenges of reliable data acquisition. To pave the way for a practical application of these findings in breeding, we then investigated the heritability (i.e., the share of genotypic variation on the observed phenotypic variation) of the accounted traits. By elaborating comparable test protocols and compiling data from over 4,000 colonies, we could, for the first time, demonstrate that recapping of infested cells and decreased reproductive success of mites are heritable (and thus selectable) traits in managed honeybee populations. My thesis proves the importance of recapping and decreased mite reproduction as resistance traits and therefore valuable goals for breeding efforts. In this regard, I shed light on the underlying mechanisms of both traits, and present clear evidence for their interaction and heritability.},
  subject      = {Varroa destructor},
  language  = {en}
}
@phdthesis{Fischer2024,
  author    = {Fischer, Katrin},
  title     = {Der Hervorgang der Welt aus Gott. Die Rezeption von Avicennas Ontologie bei Dominicus Gundisalvi, Wilhelm von Auvergne und Heinrich von Gent},
  publisher = {W{\"u}rzburg University Press},
  address   = {W{\"u}rzburg},
  isbn      = {978-3-95826-244-7},
  doi       = {10.25972/WUP-978-3-95826-245-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-351705},
  school      = {W{\"u}rzburg University Press},
  pages     = {IV, 368},
  year      = {2024},
  abstract  = {Avicenna (Ibn Sīnā, 980-1037) entwickelt vornehmlich in Kapitel I.5 und erg{\"a}nzend in den Kapiteln V.1 und 2 seiner Metaphysik (al-Ilāhiyyāt) - dem vierten Teil seiner philosophischen Summe Buch der Heilung (Kitāb al-Šifāʾ) - den Grundgedanken seiner Ontologie: die Distinktion von Sein und Wesen. Diese Lehre hat er als erster Denker zu einer eigenst{\"a}ndigen ontologischen Theorie ausgearbeitet und auf ihrer Basis eine Modalontologie entwickelt. Sie sollte zu einem seiner bekanntesten und einflussreichsten Lehrst{\"u}cke werden - nicht nur in der arabischen und hebr{\"a}ischen Tradition, sondern auch in der lateinischen. F{\"u}r Gelehrte, die von einer monotheistischen Weltanschauung gepr{\"a}gt sind, liegt die enorme Attraktivit{\"a}t der avicennischen Ontologie darin, dass sich aus der Sein-Wesen-Distinktion rein rational die wichtigsten Aspekte der Beziehung ableiten lassen, in der Gott und Welt zueinander stehen, wenn man diese Beziehung im Hinblick auf das Sein betrachtet. Mit der {\"U}bernahme der Ontologie Avicennas vermag man als christlicher Denker das eigene Modell der Wirklichkeit rational-argumentativ zu begr{\"u}nden, ohne in Autorit{\"a}tsargumenten auf die Offenbarung zur{\"u}ckgreifen zu m{\"u}ssen. Dies kommt dem Modell insofern zugute, als die rationale Fundierung dazu dient, es zu st{\"a}rken und den Glauben mittels der Vernunft besser zu begreifen - freilich ohne ihn dadurch zu rechtfertigen. Angesichts der Tatsache, dass Avicennas Ontologie bei den lateinischen Denkern stark rezipiert wurde, stellt sich f{\"u}r mich die zentrale Frage, die ich in dieser Arbeit verfolge: Wie weit kann man als christlicher Denker mit Avicenna gehen, wenn man dessen Ontologie her-anzieht, um das Verh{\"a}ltnis von Gott und Welt zu erkl{\"a}ren? Mich interessiert vor allem, an welchen Stellen und aus welchen Motiven ein Denker Modifikationen an der avicennischen Theorie vornimmt, sie anders als andere interpretiert oder g{\"a}nzlich mit ihr bricht. Was be-deuten diese {\"A}nderungen inhaltlich? Und insbesondere: Wie werden sie rational gerechtfertigt? Da Ontologie, Theologie und Kosmogonie miteinander verschr{\"a}nkt sind, wirken sich grundlegende Annahmen der Ontologie auch auf die beiden anderen Bereiche aus. Diese Auswirkungen nehme ich ebenfalls in den Blick. Meine Fragen trage ich an die Theorien dreier ausgew{\"a}hlter Denker der lateinisch-christlichen Tradition heran: Dominicus Gundisalvi († ca. 1190), Wilhelm von Auvergne (†1249) und Heinrich von Gent (†1293). Alle drei Denker sind in unterschiedliche Phasen der Rezeption von Avicennas Metaphysik im lateinischen Westen zu verorten. F{\"u}r jeden Autor untersuche ich zun{\"a}chst, inwiefern seine Ontologie von Avicennas Lehre beeinflusst ist und in welchem Verh{\"a}ltnis Gott und Welt zueinander stehen. Ausgehend davon verfolge ich anschließend, in wie weit der jeweilige Denker das in der Ontologie entwickelte Konzept eines durch sich selbst notwendig Seienden f{\"u}r Gott von Avicenna {\"u}bernimmt und wie er die Spannungen zwischen avicennischer und christlicher Lehre zu l{\"o}sen versucht, die sich beispielsweise hinsichtlich der Trinit{\"a}tstheologie ergeben. Sodann lege ich dar, wie sich die einzelnen Autoren im Unterschied zu Avicenna Gottes Wirken ad extra vorstellen, auf welche Weise sie ihr eigenes Modell rechtfertigen und damit verbunden Avicenna kritisieren. Umgekehrt werde ich ausgehend von Avicennas Standpunkt die Lehren der christlichen Denker kritisch befragen. Die Kapitel meiner Arbeit widmen sich jeweils einem Autor und sind meiner Fragestellung entsprechend parallel zueinander in einen Abschnitt zur Ontologie, Theologie und Kosmogonie unterteilt.},
  subject      = {Avicenna},
  language  = {de}
}
@phdthesis{Rehlinghaus2024,
  author    = {Rehlinghaus, Christine},
  title     = {Retrospektive Evaluation der intraven{\"o}sen Dexamethason- bzw. Methylprednisolon-Pulstherapie bei ausgepr{\"a}gter Alopecia areata},
  doi       = {10.25972/OPUS-36071},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360711},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Hintergrund: Bei der Entscheidung f{\"u}r eine intraven{\"o}se Kortikosteroid-Pulstherapie bei schweren Formen der AA ist die Abw{\"a}gung von Therapieaufwand, Nebenwirkungen und Risiken einerseits und der Erfolgsaussicht andererseits von zentraler Bedeutung. Ziel: Ziel dieser retrospektiven Analyse war es daher, die Wirksamkeit und Sicherheit der intraven{\"o}sen Kortikosteroid-Pulstherapie bei Patient:innen mit ausgepr{\"a}gter AA klinikintern als qualit{\"a}tssichernde Maßnahme zu untersuchen, prognostisch bedeutsame Faktoren f{\"u}r den Therapieeffekt zu ermitteln und hierdurch die beste Indikation herauszuarbeiten. Methode: 126 Patient:innen (13 Kinder und Jugendliche) erhielten Dexamethason 100 mg (122 Patienten) oder Methylprednisolon 20-30 mg/kg/KG (max. 1000 mg, 4 Patienten) an drei aufeinanderfolgenden Tagen f{\"u}r ein bis drei Zyklen. Ergebnisse: Patienten mit einer AA partialis bzw. diffusa zeigten im Hinblick auf ein vollst{\"a}ndiges oder kosmetisch akzeptables Wiederwachstum die besten Ansprechraten (44,3\%, n=43). Unter den Ophiasis-Patienten und den Patienten mit AA totalis/universalis sprach nur etwa ein Viertel auf die Therapie an (Ophiasis 23,8\%, n=5; AA totalis/universalis: 25\%, n=2). Schwerwiegende unerw{\"u}nschte Nebenwirkungen wurden nicht beobachtet. Schlussfolgerung: In der vorliegenden Untersuchung ließen sich eine l{\"a}ngere Bestandsdauer der Erkrankung und Erkrankungsepisode ({\"u}ber 6 Monate), ein schwerer Auspr{\"a}gungsgrad (Ophiasis, AA totalis/universalis) und krankheitstypische Nagelver{\"a}nderungen als wichtige ung{\"u}nstige prognostische Faktoren nachweisen. Dagegen wirkten sich die untersuchten Kriterien Alter, Geschlecht, atopisches Ekzem und andere Erkrankungen des atopischen Formenkreises, Schilddr{\"u}sen- und Autoimmunerkrankungen in der Eigenanamnese sowie AA in der Familienanamnese nicht negativ auf den Behandlungserfolg aus. Patienten mit AA partialis und einer Bestandsdauer der AA von maximal 6 Monaten haben die besten Erfolgsaussichten.},
  subject      = {Alopecia areata},
  language  = {de}
}
@phdthesis{Fieber2024,
  author    = {Fieber, Tabea},
  title     = {Retrospektive unizentrische Analyse des Komplikationsmanagements bei Anastomoseninsuffizienz nach linksseitiger Kolon- und Rektumresektion},
  doi       = {10.25972/OPUS-36073},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360730},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Eine gef{\"u}rchtete Komplikation nach Resektionen am Kolon mit Wiederherstellung der Kontinuit{\"a}t ist das Auftreten einer Anastomoseninsuffizienz (AI). Der Prozess der Diagnosestellung und das therapeutische Vorgehen sind zentrumsspezifisch und sehr heterogen. Ziel dieser Promotionsarbeit war die deskriptive Darstellung der Pr{\"a}valenz, Diagnostik und Therapie von AI, um anhand dieser Daten ein bestimmtes zu favorisierendes Vorgehen zur AI-Behandlung herauszuarbeiten. Es wurde eine retrospektive unizentrische Analyse durchgef{\"u}hrt. Diese umfasste eine Kohorte von 744 Patienten, welche von 2009 bis 2013 am Universit{\"a}tsklinikum W{\"u}rzburg unter Kontinuit{\"a}tserhalt kolorektal reseziert wurden. Es erfolgte eine deskriptive und statistische Auswertung mittels uni- und multivariater Analysen in Bezug auf Demographie, Risikofaktoren f{\"u}r die Entwicklung einer AI und den Erfolg der einzelnen Therapiekonzepte. W{\"a}hrend der Nachbeobachtungsphase vom im Mittel 2,5 Jahren entwickelten 10,48\% der Patienten eine AI. 60\% der Insuffizienzen wurden w{\"a}hrend der ersten 7 postoperativen Tage detektiert. Als Risikofaktoren konnten indikationsunabh{\"a}ngig m{\"a}nnliches Geschlecht, offener Zugangsweg und pulmonale Erkrankungen herausgearbeitet werden. Indikationsspezifisch zeigte sich eine Zunahme des AI-Risikos bei Divertikulitis-Patienten mit pulmonalen Erkrankungen (OR 4,5) und Cortisoneinnahme (OR 5,4). Auff{\"a}llig wurden Patienten mit AI durch heterogene und teils unspezifische Symptome - am h{\"a}ufigsten durch Fieber (28,21\%) und auff{\"a}llige Laborwerte (48,72\%). Eine folgende CT-Diagnostik best{\"a}tigte die Diagnose in 76,32\% der F{\"a}lle und war in 24,48\% falsch negativ. Patienten mit schlechtem AZ bei Diagnose der AI zeigten eine signifikant h{\"o}here Mortalit{\"a}t. Ein protektives Stoma konnte eine AI nicht verhindern, aber ihre Symptome und die Schwere des Verlaufs abmildern. Gemessen an der {\"U}berlebensrate und der Revisionspflichtigkeit unterschieden sich die durchgef{\"u}hrten Maßnahmen beim Versuch der kontinuit{\"a}tserhaltenden Therapie nicht in Bezug auf den Erfolg der Therapie. Wie Insuffizienz- und Mortalit{\"a}tsrate nach AI zeigen, ist diese unizentrische Analyse international vergleichbar. Die Ableitung einer generellen Empfehlung zur therapeutischen Vorgehensweise bei AI ist nicht m{\"o}glich. Vielmehr sind alle dargestellten Maßnahmen zur Beherrschung der AI sinnvoll, w{\"a}hrend die Wahl der Vorgehensweise weiterhin eine Individualentscheidung bleibt.},
  subject      = {Darmanastomose},
  language  = {de}
}
@phdthesis{Braehler2024,
  author    = {Br{\"a}hler, Michael},
  title     = {Bemessungsgrundlagen- und Tarifeffekte in der deutschen Alterssicherung - Eine modelltheoretische Kennzahlenanalyse des Steuer- und Sozialversicherungsrechts},
  publisher = {W{\"u}rzburg University Press},
  address   = {W{\"u}rzburg},
  isbn      = {978-3-95826-232-4},
  issn      = {2627-129X},
  doi       = {10.25972/WUP-978-3-95826-233-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-330681},
  school      = {W{\"u}rzburg University Press},
  pages     = {XXXI, 193},
  year      = {2024},
  abstract  = {In der vorliegenden Studie wird ein entscheidungsmodelltheoretischer Ansatz verwendet, um unter Vernachl{\"a}ssigung von Unsicherheit und Risiko Kennzahlen zu entwickeln, die verschiedene Formen der Altersvorsorge miteinander vergleichbar machen. Zu diesem Zweck werden die steuer- und sozialversicherungsrechtlichen Grundlagen f{\"u}r ausgew{\"a}hlte Altersvorsorgeformen (gesetzliche Rentenversicherung, Basisrentenversicherung, zulagengef{\"o}rderte Altersvorsorge, betriebliche Altersversorgung und private Rentenversicherung) im Rechtsrahmen des Jahres 2020 erl{\"a}utert. Darauf aufbauend wird ein eigenes System von Kennzahlen entwickelt, um die Vor- und Nachteile der jeweiligen Alterssicherungsform zu quantifizieren. Die Ergebnisse werden anhand von stilisierten Modellbiografien pr{\"a}sentiert und diskutiert. Eine abschließende Gesamtw{\"u}rdigung fasst schließlich wesentliche Erkenntnisse zusammen.},
  subject      = {Rentenversicherung},
  language  = {de}
}
@phdthesis{Gronemeyer2024,
  author    = {Gronemeyer, Karen},
  title     = {Kardiovaskul{\"a}re und renale Komorbidit{\"a}ten in Zusammenhang mit chronischem Hypoparathyreoidismus},
  doi       = {10.25972/OPUS-36069},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360693},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Der cHPT ist eine seltene Erkrankung, die durch zu niedriges Kalzium im Serum aufgrund einer zu geringen PTH-Sekretion {\"u}ber 6 Monate charakterisiert ist. Auch bei Patienten mit einem gut kontrollierten cHPT treten Komorbidit{\"a}ten und Langzeitkomplikationen auf, die jedoch bisher kaum in prospektiven Studien untersucht wurden. Ziel dieser Arbeit war es daher, im Rahmen einer systematischen und prospektiv erfassten Studie das Auftreten kardiovaskul{\"a}rer und renaler Komorbidit{\"a}ten bei Patienten mit cHPT zu untersuchen und m{\"o}gliche Pr{\"a}diktoren f{\"u}r diese zu ermitteln. Außerdem erfolgte ein Vergleich mit gematchten Kontrollgruppen der deutschen Normalbev{\"o}lkerung mithilfe der SHIP-TREND Studie. Patienten mit cHPT zeigten eine signifikant h{\"o}here QTc-Zeit, eine h{\"o}here Pr{\"a}valenz f{\"u}r QTc-Zeit-Verl{\"a}ngerung und signifikant h{\"o}here systolische und diastolische Blutdruckwerte trotz tendenziell, jedoch nicht signifikant, h{\"a}ufigerer Einnahme antihypertensiver Medikamente. In der Echokardiographie lagen eine geringere linksventrikul{\"a}re Masse, eine geringere Pr{\"a}valenz f{\"u}r linksventrikul{\"a}re Hypertrophie und signifikant h{\"a}ufiger Klappenstenosen vor. Eine renale Insuffizienz lag mit 21\% der Patienten mit cHPT signifikant h{\"a}ufiger als bei gesunden Kontrollpersonen vor. Die Pr{\"a}valenz renaler Kalzifikationen betrug 9,6\%. M{\"o}gliche Risikofaktoren f{\"u}r das Auftreten kardiovaskul{\"a}rer und renaler Komorbidit{\"a}ten bei cHPT sind weiterhin unklar. In dieser Studie zeigte sich eine m{\"o}gliche Assoziation zwischen den Elektrolytst{\"o}rungen wie Hyperphosphat{\"a}mie und Hypomagnesi{\"a}mie, der Hyperkalziurie und dem PTH-Mangel mit valvul{\"a}ren, vaskul{\"a}ren und renalen Kalzifikationen sowie den Blutdruckwerten und der Nierenfunktion. Demnach erscheint eine {\"U}berwachung der Serumelektrolyte sowie der Kalziumausscheidung im Urin notwendig und essenziell. Auch die Bedeutung der PTH-Ersatztherapie ist weiterhin im Hinblick auf die Pr{\"a}vention kardiovaskul{\"a}rer und renaler Erkrankungen unklar.},
  subject      = {Hypoparathyreoidismus},
  language  = {de}
}
@phdthesis{Krause2024,
  author    = {Krause, Julian},
  title     = {Auswirkungen des Klimawandels auf charakteristische B{\"o}den in Unterfranken unter Ber{\"u}cksichtigung bodenhydrologischer Monitoringdaten (2018 bis 2022)},
  doi       = {10.25972/OPUS-36066},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360668},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die mit dem Klimawandel einhergehenden Umweltver{\"a}nderungen, wie steigende Temperaturen, Abnahme der Sommer- und Zunahme der Winterniederschl{\"a}ge, h{\"a}ufigere und l{\"a}ngere Trockenperioden, zunehmende Starkniederschl{\"a}ge, St{\"u}rme und Hitzewellen betreffen besonders den Bodenwasserhaushalt in seiner zentralen Regelungsfunktion f{\"u}r den Landschaftswasserhaushalt. Von der Wasserverf{\"u}gbarkeit im Boden h{\"a}ngen zu einem sehr hohen Grad auch die Ertr{\"a}ge der Land- und Forstwirtschaft ab. Eine besonders große Bedeutung kommt dabei der Wasserspeicherkapazit{\"a}t der B{\"o}den zu, da w{\"a}hrend einer Trockenphase die effektiven Niederschl{\"a}ge den Wasserbedarf der Pflanzen nicht decken k{\"o}nnen und das bereits gespeicherte Bodenwasser das {\"U}berleben der Pflanzen sicherstellen kann. F{\"u}r die land- und forstwirtschaftlichen Akteure sind in diesem Kontext quantitative und qualitative Aussagen zu den Auswirkungen des Klimawandels auf den Boden essenziell, um die notwendigen Anpassungsmaßnahmen f{\"u}r ihre Betriebe treffen zu k{\"o}nnen. Zielsetzungen der vorliegenden Arbeit bestehen darin, die Dynamik der Bodenfeuchte in unterfr{\"a}nkischen B{\"o}den besser zu verstehen, die Datenlage zum Verlauf der Bodenfeuchte zu verbessern und die Auswirkungen von prognostizierten klimatischen Parametern absch{\"a}tzen zu k{\"o}nnen. Hierzu wurden an sechs f{\"u}r ihre jeweiligen Naturr{\"a}ume und hinsichtlich ihrer anthropogenen Nutzung charakteristischen Standorten meteorologisch-bodenhydrologische Messstationen installiert. Die Messstationen befinden sich in einem Rigosol auf Buntsandstein in einem Weinberg bei B{\"u}rgstadt sowie auf einer Parabraunerde im L{\"o}ssgebiet bei Herchsheim unter Ackernutzung. Am {\"U}bergang von Muschelkalk in Keuper befinden sich die Stationen in Obbach, wo eine Braunerde unter Ackernutzung vorliegt und im Forst des Universit{\"a}tswalds Sailershausen werden die Untersuchungen in einer Braunerde-Terra fusca durchgef{\"u}hrt. Im Forst befinden sich auch die Stationen in Oberrimbach mit Braunerden aus Sandsteinkeuper und in Willmars mit Braunerden aus Buntsandstein. Der Beobachtungszeitraum dieser Arbeit reicht von Juli 2018 bis November 2022. In diesen Zeitraum fiel die dreij{\"a}hrige D{\"u}rre von 2018 bis 2020, das Jahr 2021 mit einem durchschnittlichen Witterungsverlauf und das D{\"u}rrejahr 2022. Das Langzeitmonitoring wurde von umfangreichen Gel{\"a}nde- und Laboranalysen der grundlegenden bodenkundlichen Parameter der Bodenprofile und der Standorte begleitet. Die bodengeographischen-geomorphologischen Standortanalysen bilden zusammen mit den qualitativen Auswertungen der Bodenfeuchtezeitreihen die Grundlage f{\"u}r Einsch{\"a}tzungen zu den Auswirkungen des Klimawandels auf den Bodenwasserhaushalt. Verl{\"a}ssliche Aussagen zum Bodenwasserhaushalt k{\"o}nnen nur auf Grundlage von zeitlich und r{\"a}umlich hoch aufgel{\"o}sten Daten getroffen werden. Bodenfeuchtezeitreihen zusammen mit den bodenphysikalischen Daten lagen in dieser Datenqualit{\"a}t f{\"u}r Unterfranken bisher nur sehr vereinzelt vor. Die vorliegenden Ergebnisse zeigen, dass die untersuchten B{\"o}den entsprechend den jeweiligen naturr{\"a}umlichen Gegebenheiten sehr unterschiedliche bodenhydrologische Eigenschaften aufweisen. W{\"a}hrend langer Trockenphasen k{\"o}nnen beispielsweise die Parabraunerden am Standort Herchsheim wegen ihrer h{\"o}heren Wasserspeicherkapazit{\"a}t die Pflanzen l{\"a}nger mit Wasser versorgen als die sandigen Braunerden am Standort Oberrimbach. Die Bodenfeuchteregime im Beobachtungszeitraum waren sehr stark vom Witterungsverlauf einzelner Jahre abh{\"a}ngig. Das Bodenfeuchteregime bei einem durchschnittlichen Witterungsverlauf wie in 2021 zeichnet sich durch eine langsame Abnahme der Bodenfeuchte ab Beginn der Vegetationsperiode im Fr{\"u}hjahr aus. Regelm{\"a}ßige Niederschl{\"a}ge im Fr{\"u}hjahr f{\"u}llen den oberfl{\"a}chennahen Bodenwasserspeicher immer wieder auf und sichern den Bodenwasservorrat in der Tiefe bis in den Hochsommer. Im Hochsommer k{\"o}nnen Pflanzen dann w{\"a}hrend der Trockenphasen ihren Wasserbedarf aus den tieferen Horizonten decken. Im Gegensatz dazu nimmt die Bodenfeuchte in D{\"u}rrejahren wie 2018 bis 2020 oder 2022 bereits im Fr{\"u}hjahr bis in die untersten Horizonte stark ab. Die nutzbare Feldkapazit{\"a}t ist zum Teil schon im Juni weitgehend ausgesch{\"o}pft, womit f{\"u}r sp{\"a}tere Trockenphasen kein Bodenwasser mehr zur Verf{\"u}gung steht. Die Herbst- und Winterniederschl{\"a}ge s{\"a}ttigen den Bodenwasservorrat wieder bis zur Feldkapazit{\"a}t auf. Bei tiefreichender Ersch{\"o}pfung des Bodenwassers wurde die Feldkapazit{\"a}t erst im Januar oder Februar erreicht. Im Zuge der land- und forstwirtschaftlichen Nutzung ist eine gute Datenlage zu den bodenkundlichen und stand{\"o}rtlichen Gegebenheiten f{\"u}r klimaadaptierte Anpassungsstrategien essentiell. Wichtige Zielsetzungen bestehen grunds{\"a}tzlich in der Erhaltung der Bodenfunktionen, in der Verbesserung der Infiltrationskapazit{\"a}t und Wasserspeicherkapazit{\"a}t. Hier kommt dem Boden als interaktive Austauschfl{\"a}che zwischen den Sph{\"a}ren und damit dem Bodenschutz eine zentrale Bedeutung zu. Die in Zukunft erwarteten klimatischen Bedingungen stellen an jeden Boden andere Herausforderungen, welchen mit stand{\"o}rtlich abgestimmten Bodenschutzmaßnahmen begegnet werden kann.},
  subject      = {Bodengeografie},
  language  = {de}
}
@phdthesis{Keicher2024,
  author    = {Keicher, Franca},
  title     = {Muskul{\"a}re Einfl{\"u}sse der Rotatorenmanschette auf die Early Onset Arthrose der Schulter},
  doi       = {10.25972/OPUS-36055},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360557},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Introduction: The etiology of early onset shoulder arthritis (EOA) remains unclear. Due to the influence of the muscles of the rotator cuff (RC) on glenohumeral kinematics, muscular causes are being discussed. The aim of the study was to identify corresponding factors on EOA based on volume measurements of the RC and examinations of the adjacent bony structures in MRI imaging, as well as the collection of patient-specific characteristics. Methods: In a case-control study, shoulders of 15 patients (14 men, 1 woman) with shoulder arthritis before the age of 60 and 13 control subjects (13 men) were examined. Anthropometric body measurements and clinical characteristics were collected. The volumes of the RC were calculated using manual tracing of the individual muscle cross- sections on MRI scans. In addition, the angles between the coracoid or scapular spine and scapular body were measured. The position of the scapula to the thorax was determined by recording the angle of the scapula to the plane of the table. The glenoid retroversion, morphological types, and humeral head subluxation were also collected. The analysis was conducted using descriptive and comparative statistical methods, as well as logistic and linear regression analyses. Results: The volumes of the RC did not differ significantly between the patients with EOA and the control subjects, either in absolute terms or in relative proportions. However, significantly higher values of thorax circumference and diameter, body weight, and BMI were found in the diseased individuals compared to the controls. Furthermore, these individuals were significantly more likely to have occupations that expended more than 1400 kcal per day. The risk of EOA increased with the steeper angle of the scapula to the thorax. Patients with B2-glenoid had significantly larger angles between the coracoid and scapular body as well as higher values of transverse thorax diameter, than those with B1-glenoid. Regardless of whether EOA was present or not, engaging in overhead sports was associated with a higher subluxation index. Conclusion: While the RC did not show any abnormalities in EOA patients, male gender, BMI, thoracic shape and scapular position, as well as certain occupations and sports, were associated with EOA. Further studies are needed to investigate these risk factors in EOA more precisely and develop possible treatment concepts. Peripheral shoulder muscles (such as teres major or pectoralis major) should also be included in the investigations.},
  subject      = {Arthrose},
  language  = {de}
}