@phdthesis{Oberdorf2022,
  author    = {Oberdorf, Felix},
  title     = {Design and Evaluation of Data-Driven Enterprise Process Monitoring Systems},
  doi       = {10.25972/OPUS-29853},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-298531},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Increasing global competition forces organizations to improve their processes to gain a competitive advantage. In the manufacturing sector, this is facilitated through tremendous digital transformation. Fundamental components in such digitalized environments are process-aware information systems that record the execution of business processes, assist in process automation, and unlock the potential to analyze processes. However, most enterprise information systems focus on informational aspects, process automation, or data collection but do not tap into predictive or prescriptive analytics to foster data-driven decision-making. Therefore, this dissertation is set out to investigate the design of analytics-enabled information systems in five independent parts, which step-wise introduce analytics capabilities and assess potential opportunities for process improvement in real-world scenarios. To set up and extend analytics-enabled information systems, an essential prerequisite is identifying success factors, which we identify in the context of process mining as a descriptive analytics technique. We combine an established process mining framework and a success model to provide a structured approach for assessing success factors and identifying challenges, motivations, and perceived business value of process mining from employees across organizations as well as process mining experts and consultants. We extend the existing success model and provide lessons for business value generation through process mining based on the derived findings. To assist the realization of process mining enabled business value, we design an artifact for context-aware process mining. The artifact combines standard process logs with additional context information to assist the automated identification of process realization paths associated with specific context events. Yet, realizing business value is a challenging task, as transforming processes based on informational insights is time-consuming. To overcome this, we showcase the development of a predictive process monitoring system for disruption handling in a production environment. The system leverages state-of-the-art machine learning algorithms for disruption type classification and duration prediction. It combines the algorithms with additional organizational data sources and a simple assignment procedure to assist the disruption handling process. The design of such a system and analytics models is a challenging task, which we address by engineering a five-phase method for predictive end-to-end enterprise process network monitoring leveraging multi-headed deep neural networks. The method facilitates the integration of heterogeneous data sources through dedicated neural network input heads, which are concatenated for a prediction. An evaluation based on a real-world use-case highlights the superior performance of the resulting multi-headed network. Even the improved model performance provides no perfect results, and thus decisions about assigning agents to solve disruptions have to be made under uncertainty. Mathematical models can assist here, but due to complex real-world conditions, the number of potential scenarios massively increases and limits the solution of assignment models. To overcome this and tap into the potential of prescriptive process monitoring systems, we set out a data-driven approximate dynamic stochastic programming approach, which incorporates multiple uncertainties for an assignment decision. The resulting model has significant performance improvement and ultimately highlights the particular importance of analytics-enabled information systems for organizational process improvement.},
  subject      = {Operations Management},
  language  = {en}
}
@phdthesis{Greving2022,
  author    = {Greving, Carla Elisabeth},
  title     = {Improving Learning from Texts: Distributed Practice and Distributed Learning as Desirable Difficulty in Reading Single and Multiple Texts},
  doi       = {10.25972/OPUS-29685},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296859},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Distributed practice is a well-known learning strategy whose beneficial effects on long-term learning are well proven by various experiments. In learning from texts, the benefits of distribution might even go beyond distributed practice, i.e. distribution of repeated materials. In realistic learning scenarios as for example school or university learning, the reader might read multiple texts that not repeat but complement each other. Therefore, distribution might also be implemented between multiple texts and benefit long-term learning in analogy to distributed practice. The assumption of beneficial effects of this distributed learning can be deduced from theories about text comprehension as the landscape model of reading (van den Broek et al., 1996) in combination with theories of desirable difficulties in general (R. A. Bjork \& Bjork, 1992) and distributed practice in particular (Benjamin \& Tullis, 2010). This dissertation aims to investigate (1) whether distributed learning benefits learning; (2) whether the amount of domain-specific prior knowledge moderates the effects of distribution, (3) whether distributed learning affects the learner's meta-cognitive judgments in analogy to distributed practice and (4) whether distributed practice is beneficial for seventh graders in learning from single text. In Experiment 1, seventh graders read two complementary texts either massed or distributed by a lag of one week between the texts. Learning outcomes were measured immediately after reading the second text and one week later. Judgements of learning were assessed immediately after each text. Experiment 2 replicated the paradigm of Experiment 1 while shortening the lag between the texts in the distributed condition to 15 min. In both experiments, an interaction effect between learning condition (distributed vs. massed) and retention interval (immediate vs. delayed) was found. In the distributed condition, the participants showed no decrease in performance between the two tests, whereas participants in the massed condition did. However, no beneficial effects were found in the delayed test for the distributed condition but even detrimental effects for the distributed condition in the immediate test. In Experiment 1, participants in the distributed condition perceived learning as less difficult but predicted lower success than the participants in the massed condition. Experiment 3 replicated the paradigm of Experiment 1 with university students in the laboratory. In the preregistered Experiment 4, an additional retention interval of two weeks was realized. In both experiments, the same interaction between learning condition and retention interval was found. In Experiment 3, the participants in the distributed condition again showed no decrease in performance between the two tests, whereas participants in the massed condition did. However, even at the longer retention interval in Experiment 4, no beneficial effects were found for the distributed condition. Domain-specific prior knowledge was positively associated with test performance in both experiments. In Experiment 4, the participants with low prior knowledge seemed to be impaired by distributed learning, whereas no difference was found for participants with medium or high prior knowledge. In the preregistered Experiment 5, seventh graders read a single text twice. The rereading took place either massed or distributed with one week. Immediately after rereading, judgements of learning were assessed. Learning outcomes were assessed four min after second reading or one week later. Participants in the distributed condition predicted lower learning success than participants in the massed condition. An interaction effect between learning condition and retention interval was found, but no advantage for the distributed condition. Participants with low domain-specific prior knowledge showed lower performance in short-answer questions in the distributed condition than in the massed condition. Overall, the results seem less encouraging regarding the effectiveness of distribution on learning from single and multiple texts. However, the experiments reported here can be perceived as first step in the realistic investigation of distribution in learning from texts.},
  subject      = {Textverstehen},
  language  = {en}
}
@phdthesis{Bangalore2022,
  author    = {Bangalore, Disha Mohan},
  title     = {Mechanistic studies of protein-DNA interactions by single molecule atomic force microscopy},
  doi       = {10.25972/OPUS-25204},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252047},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Protein-DNA interactions are central to many biological processes and form the bedrock of gene transcription, DNA replication, and DNA repair processes. Many proteins recognize specific sequences in DNA- a restriction enzyme must only cut at the correct sequence and a transcription factor should bind at its consensus sequence. Some proteins are designed to bind to specific structural or chemical features in DNA, such as DNA repair proteins and some DNA modifying enzymes. Target-specific DNA binding proteins initially bind to non-specific DNA and then search for their target sites through different types of diffusion mechanisms. Atomic force microscopy (AFM) is a single-molecule technique that is specifically well-suited to resolve the distinct states of target-specific as well as nonspecific protein-DNA interactions that are vital for a deeper insight into the target site search mechanisms of these enzymes. In this thesis, protein systems involved in epigenetic regulation, base excision repair (BER), and transcription are investigated by single-molecule AFM analyses complemented by biochemical and biophysical experiments. The first chapter of this thesis narrates the establishment of a novel, user-unbiased MatLab-based tool for automated DNA bend angle measurements on AFM data. This tool has then been employed to study the initial lesion detection step of several DNA glycosylases. These results promoted a model describing the altered plasticities of DNA at the target lesions of DNA glycosylases as the fundamental mechanism for their enhanced efficiency of lesion detection. In the second chapter of this thesis, the novel automated tool has been further extended to provide protein binding positions on the DNA along with corresponding DNA bend angles and applied to the study of DNMT3A DNA methyltransferase. These AFM studies revealed preferential co-methylation at specific, defined distances between two CpG sites by the enzyme and when combined with biochemical analyses and structural modelling supported novel modes of CpG co-methylation by DNMT3A. In the third chapter of this thesis, the role of 8-oxo-guanine glycosylase (hOGG1) in Myc-mediated transcription initiation has been investigated. AFM analyses revealed that in the presence of oxidative damage in DNA, Myc is recruited to its target site (E-box) by hOGG1 through direct protein-protein interactions, specifically under oxidizing conditions. Intriguingly, oxidation of hOGG1 was further observed to result in dimerization of hOGG1, which may also play a role in the mechanism of transcription regulation by hOGG1 under oxidative stress.},
  subject      = {Transcription},
  language  = {en}
}
@phdthesis{Schloer2022,
  author    = {Schl{\"o}r, Daniel},
  title     = {Detecting Anomalies in Transaction Data},
  doi       = {10.25972/OPUS-29856},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-298569},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Detecting anomalies in transaction data is an important task with a high potential to avoid financial loss due to irregularities deliberately or inadvertently carried out, such as credit card fraud, occupational fraud in companies or ordering and accounting errors. With ongoing digitization of our world, data-driven approaches, including machine learning, can draw benefit from data with less manual effort and feature engineering. A large variety of machine learning-based anomaly detection methods approach this by learning a precise model of normality from which anomalies can be distinguished. Modeling normality in transactional data, however, requires to capture distributions and dependencies within the data precisely with special attention to numerical dependencies such as quantities, prices or amounts. To implicitly model numerical dependencies, Neural Arithmetic Logic Units have been proposed as neural architecture. In practice, however, these have stability and precision issues. Therefore, we first develop an improved neural network architecture, iNALU, which is designed to better model numerical dependencies as found in transaction data. We compare this architecture to the previous approach and show in several experiments of varying complexity that our novel architecture provides better precision and stability. We integrate this architecture into two generative neural network models adapted for transaction data and investigate how well normal behavior is modeled. We show that both architectures can successfully model normal transaction data, with our neural architecture improving generative performance for one model. Since categorical and numerical variables are common in transaction data, but many machine learning methods only process numerical representations, we explore different representation learning techniques to transform categorical transaction data into dense numerical vectors. We extend this approach by proposing an outlier-aware discretization, thus incorporating numerical attributes into the computation of categorical embeddings, and investigate latent spaces, as well as quantitative performance for anomaly detection. Next, we evaluate different scenarios for anomaly detection on transaction data. We extend our iNALU architecture to a neural layer that can model both numerical and non-numerical dependencies and evaluate it in a supervised and one-class setting. We investigate the stability and generalizability of our approach and show that it outperforms a variety of models in the balanced supervised setting and performs comparably in the one-class setting. Finally, we evaluate three approaches to using a generative model as an anomaly detector and compare the anomaly detection performance.},
  subject      = {Anomalieerkennung},
  language  = {en}
}
@phdthesis{Zoran2022,
  author    = {Zoran, Tamara},
  title     = {Multilevel analysis of the human immune response to \(Aspergillus\) \(fumigatus\) infection: Characteristic molecular signatures and individual risk factors},
  doi       = {10.25972/OPUS-29851},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-298512},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Although the field of fungal infections advanced tremendously, diagnosis of invasive pulmonary aspergillosis (IPA) in immunocompromised patients continues to be a challenge. Since IPA is a multifactorial disease, investigation from different aspects may provide new insights, helpful for improving IPA diagnosis. This work aimed to characterize the human immune response to Aspergillus fumigatus in a multilevel manner to identify characteristic molecular candidates and risk factors indicating IPA, which may in the future support already established diagnostic assays. We combined in vitro studies using myeloid cells infected with A. fumigatus and longitudinal case-control studies investigating patients post allogeneic stem cell transplantation (alloSCT) suffering from IPA and their match controls. Characteristic miRNA and mRNA signatures indicating A. fumigatus-infected monocyte-derived dendritic cells (moDCs) demonstrated the potential to differentiate between A. fumigatus and Escherichia coli infection. Transcriptome and protein profiling of alloSCT patients suffering from IPA and their matched controls revealed a distinctive IPA signature consisting of MMP1 induction and LGAL2 repression in combination with elevated IL-8 and caspase-3 levels. Both, in vitro and case-control studies, suggested cytokines, matrix-metallopeptidases and galectins are important in the immune response to A. fumigatus. Identified IPA characteristic molecular candidates are involved in numerous processes, thus a combination of these in a distinctive signature may increase the specificity. Finally, low monocyte counts, severe GvHD of the gut (grade ≥ 2) and etanercept administration were significantly associated with IPA diagnosis post alloSCT. Etanercept in monocyte-derived macrophages (MDM) infected with A. fumigatus downregulates genes involved in the NF-κB and TNF-α pathway and affects the secretion of CXCL10. Taken together, identified characteristic molecular signatures and risk factors indicating IPA may in the future in combination with established fungal biomarkers overcome current diagnostic challenges and help to establish tailored antifungal therapy. Therefore, further multicentre studies are encouraged to evaluate reported findings.},
  subject      = {Aspergillus fumigatus},
  language  = {en}
}
@phdthesis{Dakroub2022,
  author    = {Dakroub, Mohamad},
  title     = {Coarsened Exact Matching of Excisional to Plasma-Ablative Ab Interno Trabeculectomy},
  doi       = {10.25972/OPUS-29680},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296805},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Abstract Purpose: To compare ab interno trabeculectomy by trabecular meshwork excision to plasma-mediated ablation in primary open-angle glaucoma. Methods: Retrospectively collected data of TrabEx+ (n=56) and Trabectome (n=99) were compared by coarsened exact matching to reduce confounding and matched based on baseline intraocular pressure and age. Primary outcomes were intraocular pressure and the number of glaucoma medications. Complications and the need for additional glaucoma surgery were assessed. Patients were followed for up to one year. Results: 53 TrabEx+ could be matched to Trabectome. Baseline intraocular pressure was 16.5 ± 4.6 mmHg in both; age was 73.7 ± 8.8 years and 71.5 ± 9.9 years in TrabEx+ and Trabectome, respectively. TrabEx+ were taking more medications than Trabectome (p<0.001). Intraocular pressure was reduced to 14.8±4.3 in TrabEx+ and 13.4±3.4 in Trabectome at 6 months, and to 14.9±6.0 (p=0.13) in TrabEx+ and to 14.1±3.8 mmHg (all p<0.05) in Trabectome at 12 months. Medications were reduced at both 6 and 12 months (p< 0.05). No differences were seen between both groups at 6 and 12 months. In TrabEx+, only one serious complication occurred, and two patients required further glaucoma surgery. Conclusion: Although both groups had a baseline intraocular pressure considered low for ab interno trabeculectomy, intraocular pressure and medications were reduced further at 6 and 12 months. Intraocular pressure reduction did not reach significance in TrabEx+ at 12 months. The inter-group comparison did not reveal any significant differences. Both had a low complication rate.},
  subject      = {Glaukom},
  language  = {en}
}
@phdthesis{Guentzel2022,
  author    = {G{\"u}ntzel, Paul Mathias},
  title     = {Bioinspired Ion Pairs Transforming Poorly Water-soluble Compounds into Protic Ionic Liquids and Deep Eutectic Solvents},
  doi       = {10.25972/OPUS-21980},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219806},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Microbial, mammalian and plant cells produce and contain secondary metabolites, which typically are soluble in water to prevent cell damage by crystallization. The formation of ion pairs, e.g. with carboxylic acids or mineral acids, is a natural blueprint to keep basic metabolites in solution. It was aimed at showing whether the mostly large carboxylates form soluble protic ionic liquids (PILs) with basic natural products resulting in enhanced aqueous solubility. Furthermore, their supramolecular pattern in aqueous solution was studied. Thereby, naturally occurring carboxylic acids were identified being appropriate counterions for natural basic compounds and facilitate the formation of PILs with their beneficial characteristics, like improved dissolution rate and enhanced apparent solubility.},
  subject      = {Ionic Liquids},
  language  = {en}
}
@phdthesis{Shan2022,
  author    = {Shan, Junwen},
  title     = {Tailoring Hyaluronic Acid and Gelatin for Bioprinting},
  doi       = {10.25972/OPUS-29825},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-298256},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In the field of biofabrication, biopolymer-based hydrogels are often used as bulk materials with defined structures or as bioinks. Despite their excellent biocompatibility, biopolymers need chemical modification to fulfill mechanical stability. In this thesis, the primary alcohol of hyaluronic acid was oxidized using TEMPO/TCC oxidation to generate aldehyde groups without ring-opening mechanism of glycol cleavage using sodium periodate. For crosslinking reaction of the aldehyde groups, adipic acid dihydrazide was used as bivalent crosslinker for Schiff Base chemistry. This hydrogel system with fast and reversible crosslinking mechanism was used successfully as bulk hydrogel for chondrogenic differentiation with human mesenchymal stem cells (hMSC). Gelatin was modified with pentenoic acid for crosslinking reaction via light controllable thiol-ene reaction, using thiolated 4-arm sPEG as multivalent crosslinker. Due to preservation of the thermo responsive property of gelatin by avoiding chain degradation during modification reaction, this gelatin-based hydrogel system was successfully processed via 3D printing with low polymer concentration. Good cell viability was achieved using hMSC in various concentrations after 3D bioprinting and chondrogenic differentiation showed promising results.},
  subject      = {Hydrogel},
  language  = {en}
}
@phdthesis{Burd2022,
  author    = {Burd, Paul Ray},
  title     = {Multiwavelength Probes of Physical Conditions in the Blazar Zone of AGN jets},
  doi       = {10.25972/OPUS-29700},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297001},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Context. In active galaxies, matter is accreted onto super massive black holes (SMBH). This accretion process causes a region roughly the size of our solar system to outshine the entire host galaxy, forming an active galactic nucleus (AGN). In some of these active galaxies, highly relativistic particle jets are formed parallel to the rotation axis of the super massive black hole. A fraction of these sources is observed under a small inclination angle between the pointing direction of the jet and the observing line of sight. These sources are called blazars. Due to the small inclination angle and the highly relativistic speeds of the particles in the jet, beaming effects occur in the radiation of these particles. Blazars can be subdivided into the high luminosity flat spectrum radio quasars (FSRQs) and the low luminosity BL Lacertae objects (BL Lacs). As all AGN, blazars are broadband emitters and therefore observable from the longest wavelengths in the radio regime to the shortest wavelengths in the gamma-ray regime. In this thesis I will analyze blazars at these two extremes with respect to their parsec-scale properties in the radio and their time evolution properties in gamma-ray flux. Method. In the radio regime the technique of very long baseline interferometry (VLBI) can be used in order to spatially resolve the synchrotron radiation coming from those objects down to sub-parsec scales. This information can be used to observe the time evolution of the structure of such sources. This is done in large monitoring programs such as the MOJAVE (15 GHz) and the Boston University blazar monitoring program (43 GHz). In this thesis I utilize data of 28 sources from these monitoring programs spanning 10 years of observation from 2003 to 2013, resulting in over 1800 observed epochs, to study the brightness temperature and diameter gradients of these jets. I conduct a search for systematic geometry transitions in the radio jets. The synchrotron cooling time in the radio core of the jets is used to determine the magnetic field strength in the radio core. Considering the jet geometry, these magnetic field strengths are scaled to the ergosphere of the SMBH in order to obtain the distance of the radio core to the SMBH. In the gamma-regime these blazars cannot be spatially resolved. Due to this, it is hard to put strong constrains onto where the gamma-ray emitting region is. Blazars have shown to be variable at high energies on time scales down to minutes. The nature of this variability can be studied in order to put constrains on the particle acceleration mechanism and possibly the region and size of the gamma-ray emitting region. The variability of blazars in the energy range between 0.1 GeV and 1 GeV can for example be observed with the pair-conversion telescope on board the Fermi satellite. I use 10 years of data from the Fermi-LAT (LAT: Large Area Telescope) satellite in order to study the variability of a large sample of blazars (300-800, depending on the used significance filters for data points). I quantify this variability with the Ornstein-Uhlenbeck (OU) parameters and the power spectral density (PSD) slopes. The same procedure is applied to 20 light curves available for the radio sample. Results. The diameter evolution along the jet axis of the radio sources suggests, that FSRQs feature flatter gradients than BL Lacs. Fitting these gradients, it is revealed that BL Lacs are systematically better described by a simple single power law than FSRQs. I found 9 sources with a strongly constrained geometry transition. The sources are 0219+421, 0336-019, 0415+379, 0528+134, 0836+710, 1101+384, 1156+295, 1253-055 and 2200+420. In all of these sources, the geometry transition regions are further out in the jet than the Bondi sphere. The magnetic field strengths of BL Lacs is systematically larger than that of FSRQs. However the scaling of these fields suggest that the radio cores of BL Lac objects are closer to the SMBHs than the radio cores of FSRQs. Analyzing the variability of Fermi-LAT light curves yields consistent results for all samples. FSRQs show systematically steeper PSD slopes and feature OU parameters more favorable to strong variability than BL Lacs. The Fermi-LAT light curves of the sub-sample of radio jets, suggest an anticorrelation between the jet complexity from the radio observations and the OU-parameters as well as the PSD slopes from the gamma-ray observations. Conclusion. The flatter diameter gradients of FSRQs suggest that these sources are more collimated further down the jet than BL Lacs. The systematically better description of the diameter and brightness temperature gradient by a single power law of BL Lacs, suggest that FSRQs are more complex with respect to the diameter evolution along the jet and the surface brightness distribution than BL Lac objects. FSRQs often feature regions where recollimation can occur in distinct knots within the jets. For the sources where a geometry transition could be constrained, the Bondi radius, being systematically smaller than the position of the transition region along the jet axis, suggest that changing pressure gradients are not the sole cause for these systematic geometry transitions. Nevertheless they may be responsible for recollimation regions, found typically downstream the jet, beyond the Bondi radius and the transition zone. The difference in the distance of the radio cores between FSRQs and BL Lacs is most likely due to the combination of differences in SMBH masses and systematically smaller jet powers in BL Lacs. The variability in energy ranges above 100 MeV and above 1 GeV-regime suggest that many light curves of BL Lac objects are more likely to be white noise while the PSD slopes and the OU parameters of FSRQ gamma-ray light curves favor stronger variability on larger time scales with respect to the time binning of the analyzed light curve. Although the anticorrelation of the jet complexity acquired from the radio observations and the PSD slopes and OU parameters from the gamma-observations suggest that more complex sources favor OU parameters and PSD slopes resulting in more variability (not white noise) it is beyond the scope of this thesis to pinpoint whether this correlation results from causation. The question whether a complex jet causes more gamma-ray variability or more gamma-ray variability causes more complex jets cannot be answered at this point. Nevertheless the computed correlation measures suggest that this dependence is most likely not linear and therefore an indication that these effects might even interact.},
  language  = {en}
}
@phdthesis{Palmisano2022,
  author    = {Palmisano, Chiara},
  title     = {Supraspinal Locomotor Network Derangements: A Multimodal Approach},
  doi       = {10.25972/OPUS-26644},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266442},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Parkinson's Disease (PD) constitutes a major healthcare burden in Europe. Accounting for aging alone, ~700,000 PD cases are predicted by 2040. This represents an approximately 56\% increase in the PD population between 2005 and 2040, with a consequent rise in annual disease-related medical costs. Gait and balance disorders are a major problem for patients with PD and their caregivers, mainly because to their correlation with falls. Falls occur as a result of a complex interaction of risk factors. Among them, Freezing of Gait (FoG) is a peculiar gait derangement characterized by a sudden and episodic inability to produce effective stepping, causing falls, mobility restrictions, poor quality of life, and increased morbidity and mortality. Between 50-70\% of PD patients have FoG and/or falls after a disease duration of 10 years, only partially and inconsistently improved by dopaminergic treatment and Deep Brain Stimulation (DBS). Treatment-induced worsening has been also observed under certain conditions. Effective treatments for gait disturbances in PD are lacking, probably because of the still poor understanding of the supraspinal locomotor network. In my thesis, I wanted to expand our knowledge of the supraspinal locomotor network and in particular the contribution of the basal ganglia to the control of locomotion. I believe this is a key step towards new preventive and personalized therapies for postural and gait problems in patients with PD and related disorders. In addition to patients with PD, my studies also included people affected by Progressive Supranuclear Palsy (PSP). PSP is a rare primary progressive parkinsonism characterized at a very early disease stage by poor balance control and frequent backwards falls, thus providing an in vivo model of dysfunctional locomotor control. I focused my attention on one of the most common motor transitions in daily living, the initiation of gait (GI). GI is an interesting motor task and a relevant paradigm to address balance and gait impairments in patients with movement disorders, as it is associated with FoG and high risk of falls. It combines a preparatory (i.e., the Anticipatory Postural Adjustments [APA]) and execution phase (the stepping) and allows the study of movement scaling and timing as an expression of muscular synergies, which follow precise and online feedback information processing and integration into established feedforward patterns of motor control. By applying a multimodal approach that combines biomechanical assessments and neuroimaging investigations, my work unveiled the fundamental contribution of striatal dopamine to GI in patients with PD. Results in patients with PSP further supported the fundamental role of the striatum in GI execution, revealing correlations between the metabolic intake of the left caudate nucleus with diverse GI measurements. This study also unveiled the interplay of additional brain areas in the motor control of GI, namely the Thalamus, the Supplementary Motor Area (SMA), and the Cingulate cortex. Involvement of cortical areas was also suggested by the analysis of GI in patients with PD and FoG. Indeed, I found major alterations in the preparatory phase of GI in these patients, possibly resulting from FoG-related deficits of the SMA. Alterations of the weight shifting preceding the stepping phase were also particularly important in PD patients with FoG, thus suggesting specific difficulties in the integration of somatosensory information at a cortical level. Of note, all patients with PD showed preserved movement timing of GI, possibly suggesting preserved and compensatory activity of the cerebellum. Postural abnormalities (i.e., increased trunk and thigh flexion) showed no relationship with GI, ruling out an adaptation of the motor pattern to the altered postural condition. In a group of PD patients implanted with DBS, I further explored the pathophysiological functioning of the locomotor network by analysing the timely activity of the Subthalamic Nucleus (STN) during static and dynamic balance control (i.e., standing and walking). For this study, I used novel DBS devices capable of delivering stimulation and simultaneously recording Local Field Potentials (LFP) of the implanted nucleus months and years after surgery. I showed a gait-related frequency shift in the STN activity of PD patients, possibly conveying cortical (feedforward) and cerebellar (feedback) information to mesencephalic locomotor areas. Based on this result, I identified for each patient a Maximally Informative Frequency (MIF) whose power changes can reliably classify standing and walking conditions. The MIF is a promising input signal for new DBS devices that can monitor LFP power modulations to timely adjust the stimulation delivery based on the ongoing motor task (e.g., gait) performed by the patient (adaptive DBS). Altogether my achievements allowed to define the role of different cortical and subcortical brain areas in locomotor control, paving the way for a better understanding of the pathophysiological dynamics of the supraspinal locomotor network and the development of tailored therapies for gait disturbances and falls prevention in PD and related disorders.},
  language  = {en}
}
@phdthesis{Ferretti2022,
  author    = {Ferretti, Pamela},
  title     = {\(Clostridioides\) \(difficile\) beyond the disease-centred perspective: Beneficial properties in healthy infants and over-diagnosis in diseased adults identified by species- and SNV-based metagenomic analysis},
  doi       = {10.25972/OPUS-25417},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254170},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Clostridioides difficile is a bacterial species well known for its ability to cause C. difficile infection (also known as CDI). The investigation of the role of this species in the human gut has been so far dominated by a disease-centred perspective, focused on studying C. difficile in relation to its associated disease. In this context, the first aim of this thesis was to combine publicly available metagenomic data to analyse the microbial composition of stool samples from patients diagnosed with CDI, with a particular focus on identifying a CDI-specific microbial signature. However, similarly to many other bacterial species inhabiting the human gut, C. difficile association with disease is not valid in absolute terms, as C. difficile can be found also among healthy subjects. Further aims of this thesis were to 1) identify potential C. difficile reservoirs by screening a wide range of habitats, hosts, body sites and age groups, and characterize the biotic context associated with C. difficile presence, and 2) investigate C. difficile within-species diversity and its toxigenic potential across different age groups. The first part of the thesis starts with the description of the concepts and definitions used to identify bacterial species and within-species diversity, and then proceeds to provide an overview of the bacterial species at the centre of my investigation, C. difficile. The first Chapter includes a detailed description of the discovery, biology and physiology of this clinically relevant species, followed by an overview of the diagnostic protocols used in the clinical setting to diagnose CDI. The second part of the thesis describes the methodology used to investigate the questions mentioned above, while the third part presents the results of such investigative effort. I first show that C. difficile could be found in only a fraction of the CDI samples and that simultaneous colonization of multiple enteropathogenic species able to cause CDI-like clinical manifestations is more common than previously thought, raising concerns about CDI overdiagnosis. I then show that the CDIassociated gut microbiome is characterized by a specific microbial signature, distinguishable from the community composition associated with non-CDI diarrhea. Beyond the nosocomial and CDI context, I show that while rarely found in adults, C. difficile is a common member of the infant gut microbiome, where its presence is associated with multiple indicators typical of a desirable healthy microbiome development. In addition, I describe C. difficile extensive carriage among asymptomatic subjects, of all age groups and a potentially novel clade of C. difficile identified exclusively among infants. Finally, I discuss the limitations, challenges and future perspectives of my investigation.},
  language  = {en}
}
@phdthesis{Knoepper2022,
  author    = {Kn{\"o}pper, Konrad},
  title     = {Lymph node heterogeneity is imprinted by unconventional T cells that are organized in functional units},
  doi       = {10.25972/OPUS-29694},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296949},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The immune system has the function to defend organisms against a variety of pathogens and malignancies. To perform this task, different parts of the immune system work in concert and influence each other to balance and optimize its functional output upon activation. One aspect that determines this output and ultimately the outcome of the infection is the tissue context in which the activation takes place. As such, it has been shown that dendritic cells can relay information from the infection sites to draining lymph nodes. This way, the ensuing adaptive immune response that is initiated by dendritic cells, is optimized to the tissue context in which the infection needs to be cleared. Here, we set out to investigate whether unconventional T cells (UTC) could have a similar function in directing a site-specific immune response. Using flow cytometry, scRNA-sequencing and functional assays we demonstrated that UTC indeed drive a characteristic immune response in lymph nodes depending on the drained tissues. This function of UTC was directly connected to their lymphatic migration from tissues to draining lymph nodes reminiscent of dendritic cells. Besides these tissue-derived UTC that migrated via the lymph, we further identified circulatory UTC that migrated between lymph nodes via the blood. Functional characterization of UTC following bacterial infection in wt and single TCR-based lineage deficient mice that lacked subgroups of UTC further revealed that both tissue-derived and circulatory UTC were organized in functional units independent of their TCR-based lineage-affiliation (MAIT, NKT, gd T cells). Specific reporter mouse models revealed that UTC within the same functional unit were also located in the same microanatomical areas of lymph nodes, further supporting their shared function. Our data show that the numbers and function of UTC were compensated in single TCR-based lineage deficient mice that lacked subgroups of UTC. Taken together, our results characterize the transcriptional landscape and migrational behavior of UTC in different lymph nodes. UTC contribute to a functional heterogeneity of lymph nodes, which in turn guides optimized, site-specific immune responses. Additionally, we propose the classification of UTC within functional units independent of their TCR-based lineage. These results add significantly to our understanding of UTC biology and have direct clinical implications. We hope that our data will guide targeted vaccination approaches and cell-based therapies to optimize immune responses against pathogens and cancer.},
  language  = {en}
}
@phdthesis{Ye2022,
  author    = {Ye, Mingyu},
  title     = {Immunotherapy with Vaccinia virus co-expressing tumor-associated antigens and mouse IL-2 cytokine in mice with mammary cancer},
  doi       = {10.25972/OPUS-25309},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-253095},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Interleukin 2 (IL-2) was the first cytokine applied for cancer treatment in human history. It has been approved as monotherapy for renal cell carcinoma and melanoma by the FDA and does mediate the regression of the tumors in patients. One of the possible mechanisms is that the administration of IL-2 led to T lymphocytes expansion, including CD4+ and CD8+ T cells. In addition, a recent study demonstrated that antigen-specific T cells could also be expanded through the induction of IL-2, which plays a crucial role in mediating tumor regression. However, despite the long-term and extensive use of IL-2 in the clinic, the ratio of patients who get a complete response was still low, and only about one-fifth of patients showed objective tumor regression. Therefore, the function of IL-2 in cancer treatment should continue to be optimized and investigated. A study by Franz O. Smith et al. has shown that the combination treatment of IL-2 and tumor-associated antigen vaccine has a strong trend to increased objective responses compared to patients with melanoma receiving IL-2 alone. Peptide vaccines are anti-cancer vaccines able to induce a powerful tumor antigenspecific immune response capable of eradicating the tumors. According to the type of antigens, peptide vaccines can be classified into two distinct categories: Tumor-associated antigens (TAA) vaccine and tumor-specific neoantigens (TSA) vaccine. Currently, Peptide vaccines are mainly investigated in phase I and phase II clinical trials of human cancer patients with various advanced cancers such as lung cancer, gastrointestinal tumors, and breast cancers. Vaccinia virus (VACV) is one of the safest viral vectors, which has been wildly used in cancer treatment and pathogen prevention. As an oncolytic vector, VACV can carry multiple large foreign genes, which enable the virus to introduce diagnostic and therapeutic agents without dramatically reducing the viral replication. Meanwhile, the recombinant vaccinia virus (rVACV) can be easily generated by homologous recombination. Here, we used the vaccinia virus as the therapeutic cancer vector, expressing mouse Interleukin 2 (IL-2) and tumor-associated antigens simultaneously to investigate the combined effect of anti-tumor immune response in the 4T1 mouse tumor model. As expected, the VACV driven mIL-2 expression remarkably increased both CD4+ and CD8+ populations in vivo, and the virus-expressed tumor-associated peptides successfully elicited theantigen-specific T cell response to inhibit the growth of tumors. Furthermore, the experiments with tumor-bearing animals showed that the mIL-2 plus tumor antigens expressing VACV vector gave a better anti-cancer response than the mIL-2 alone expressing vector. The combinations did significantly more inhibit tumor growth than mIL-2 treatment alone. Moreover, the results confirmed our previous unpublished data that the mIL-2 expression driven by synthetic early/late promoter in the Lister strain VACV could enhance the tumor regression in the 4T1 mouse model.},
  language  = {en}
}
@phdthesis{Ku2022,
  author    = {Ku, Hsing-Ping},
  title     = {Cadherin-13 Deficiency Impacts Murine Serotonergic Circuitries and Cognitive Functions},
  doi       = {10.25972/OPUS-25144},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251446},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Cadherin-13 (CDH13) is a member of the cadherin superfamily that lacks the typical transmembrane domain for classical cadherins and is instead attached to the cell membrane with a GPI-anchor. Over the years, numerous genome-wide association (GWA) studies have identified CDH13 as a risk factor for neurodevelopmental disorders, including attention- deficit/hyperactivity disorder (ADHD) and autism spectrum disorder. Further evidence using cultured cells and animal models has shown that CDH13 plays important roles in cell migration, neurite outgrowth and synaptic function of the central nervous system. Research in our laboratory demonstrated that the CDH13 deficiency resulted in increased cell density of serotonergic neurons of the dorsal raphe (DR) in developing and mature mouse brains as well as serotonergic hyperinnervation in the developing prefrontal cortex, one of the target areas of DR serotonergic neurons. In this study, the role of CDH13 was further explored using constitutive and serotonergic system-specific CDH13-deficient mouse models. Within the adult DR structure, the increased density of DR serotonergic neurons was found to be topographically restricted to the ventral and lateral-wing, but not dorsal, clusters of DR. Furthermore, serotonergic hyperinnervation was observed in the target region of DR serotonergic projection neurons in the lateral wings. Unexpectedly, these alterations were not observed in postnatal day 14 brains of CDH13-deficient mice. Additionally, behavioral assessments revealed cognitive deficits in terms of compromised learning and memory ability as well as impulsive-like behaviors in CDH13-deficient mice, indicating that the absence of CDH13 in the serotonergic system alone was sufficient to impact cognitive functions and behavioral competency. Lastly, in order to examine the organization of serotonergic circuitries systematically and to tackle limitations of conventional immunofluorescence, a pipeline of the whole-mount immunostaining in combination with the iDISCO+ based rapid tissue clearing techniques was established. This will facilitate future research of brain neurotransmitter systems at circuitry and/or whole-brain levels and provide an excellent alternative for visualizing detailed and comprehensive information about a biological system in its original space. In summary, this study provided new evidence of CDH13's contribution to proper brain development and cognitive function in mice, thereby offering insights into further advancement of therapeutic approaches for neurodevelopmental disorders.},
  language  = {en}
}
@phdthesis{Kuhlemann2022,
  author    = {Kuhlemann, Alexander},
  title     = {Bioorthogonal labeling of neuronal proteins using super-resolution fluorescence microscopy},
  doi       = {10.25972/OPUS-24373},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243731},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The synaptic cleft is of central importance for synaptic transmission, neuronal plasticity and memory and thus well studied in neurobiology. To target proteins of interest with high specificity and strong signal to noise conventional immunohistochemistry relies on the use of fluorescently labeled antibodies. However, investigations on synaptic receptors remain challenging due to the defined size of the synaptic cleft of ~20 nm between opposing pre- and postsynaptic membranes. At this limited space, antibodies bear unwanted side effects such as crosslinking, accessibility issues and a considerable linkage error between fluorophore and target of ~10 nm. With recent single molecule localization microscopy (SMLM) methods enabling localization precisions of a few nanometers, the demand for labeling approaches with minimal linkage error and reliable recognition of the target molecules rises. Within the scope of this work, different labeling techniques for super-resolution fluorescence microscopy were utilized allowing site-specific labeling of a single amino acid in synaptic proteins like kainate receptors (KARs), transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor regulatory proteins (TARPs), γ-aminobutyric acid type A receptors (GABA-ARs) and neuroligin 2 (NL2). The method exploits the incorporation of unnatural amino acids (uAAs) in the protein of interest using genetic code expansion (GCE) via amber suppression technology and subsequent labeling with tetrazine functionalized fluorophores. Implementing this technique, hard-to-target proteins such as KARs, TARPs and GABA-ARs could be labeled successfully, which could only be imaged insufficiently with conventional labeling approaches. Furthermore, functional studies involving electrophysiological characterization, as well as FRAP and FRET experiments validated that incorporation of uAAs maintains the native character of the targeted proteins. Next, the method was transferred into primary hippocampal neurons and in combination with super-resolution microscopy it was possible to resolve the nanoscale organization of γ2 and γ8 TARPs. Cluster analysis of dSTORM localization data verified synaptic accumulation of γ2, while γ8 was homogenously distributed along the neuron. Additionally, GCE and bioorthogonal labeling allowed visualization of clickable GABA-A receptors located at postsynaptic compartments in dissociated hippocampal neurons. Moreover, saturation experiments and FRET imaging of clickable multimeric receptors revealed successful binding of multiple tetrazine functionalized fluorophores to uAA-modified dimeric GABA-AR α2 subunits in close proximity (~5 nm). Further utilization of tetrazine-dyes via super-resolution microscopy methods such as dSTORM and click-ExM will provide insights to subunit arrangement in receptors in the future. This work investigated the nanoscale organization of synaptic proteins with minimal linkage error enabling new insights into receptor assembly, trafficking and recycling, as well as protein-protein interactions at synapses. Ultimately, bioorthogonal labeling can help to understand pathologies such as the limbic encephalitis associated with GABA-AR autoantibodies and is already in application for cancer therapies.},
  subject      = {microscopy},
  language  = {en}
}
@phdthesis{Hochheimer2022,
  author    = {Hochheimer, Vanessa Christine},
  title     = {Of cells and enzymes: How dermal fibroblasts can impact pain in Fabry Disease and Why looking at the 3D-structure of α-Galactosidase A may be worthwhile for clinical management of Fabry patients},
  doi       = {10.25972/OPUS-29660},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-296607},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Fabry Disease (FD) is a genetic lysosomal storage disorder based on mutations in the gene encoding α-Galactosidase A (α-GalA) leading to accumulation of globotriaosylceramide (Gb3). Missense mutations induce an amino acid exchange (AAE) in the α-GalA. Pain is a predominant symptom in FD and the pathophysiology is unclear. Skin punch biopsies were obtained from 40 adult FD patients and ten healthy controls and dermal fibroblast cultures were generated for cell culture experiments to investigate Gb3 load, gene and protein expression patterns and ion channel activity. The 3D-structure of α-GalA was downloaded into Pymol Graphics System and the AAE was depicted and located in order to investigate the correlation between the AAE location type in the α-GalA and the clinical FD phenotype. FD dermal fibroblasts showed high Gb3 load depending on treatment interval and expressed Kca1.1 channels. Activity was reduced in FD cells at baseline, but increased over-proportionately upon Gb3-cleavage by enzyme replacement therapy. Gene and protein expression of Kca1.1 was increased in FD cells. FD dermal fibroblasts showed higher gene expression of Notch1 and several cytokines. Further, it was shown that three different AAE location types can be differentiated: mutations in the active site ('active site'), those buried in the core of α-GalA ('buried') and those at another location, mostly on the protein surface ('other'). FD patients carrying active site or buried mutations showed a severe clinical phenotype with multi-organ manifestation and early disease onset. Patients with other mutations were less severely affected with oligo-organ manifestation sparing the nervous system and later disease onset. These results show that dermal fibroblasts may be involved in FD-associated pain and that stratification of FD patients carrying missense mutations by AAE location type may be an advantageous parameter that can help in the management of FD patients.},
  subject      = {Fabry-Krankheit},
  language  = {en}
}
@phdthesis{Hoeser2022,
  author    = {H{\"o}ser, Thorsten},
  title     = {Global Dynamics of the Offshore Wind Energy Sector Derived from Earth Observation Data - Deep Learning Based Object Detection Optimised with Synthetic Training Data for Offshore Wind Energy Infrastructure Extraction from Sentinel-1 Imagery},
  doi       = {10.25972/OPUS-29285},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-292857},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The expansion of renewable energies is being driven by the gradual phaseout of fossil fuels in order to reduce greenhouse gas emissions, the steadily increasing demand for energy and, more recently, by geopolitical events. The offshore wind energy sector is on the verge of a massive expansion in Europe, the United Kingdom, China, but also in the USA, South Korea and Vietnam. Accordingly, the largest marine infrastructure projects to date will be carried out in the upcoming decades, with thousands of offshore wind turbines being installed. In order to accompany this process globally and to provide a database for research, development and monitoring, this dissertation presents a deep learning-based approach for object detection that enables the derivation of spatiotemporal developments of offshore wind energy infrastructures from satellite-based radar data of the Sentinel-1 mission. For training the deep learning models for offshore wind energy infrastructure detection, an approach is presented that makes it possible to synthetically generate remote sensing data and the necessary annotation for the supervised deep learning process. In this synthetic data generation process, expert knowledge about image content and sensor acquisition techniques is made machine-readable. Finally, extensive and highly variable training data sets are generated from this knowledge representation, with which deep learning models can learn to detect objects in real-world satellite data. The method for the synthetic generation of training data based on expert knowledge offers great potential for deep learning in Earth observation. Applications of deep learning based methods can be developed and tested faster with this procedure. Furthermore, the synthetically generated and thus controllable training data offer the possibility to interpret the learning process of the optimised deep learning models. The method developed in this dissertation to create synthetic remote sensing training data was finally used to optimise deep learning models for the global detection of offshore wind energy infrastructure. For this purpose, images of the entire global coastline from ESA's Sentinel-1 radar mission were evaluated. The derived data set includes over 9,941 objects, which distinguish offshore wind turbines, transformer stations and offshore wind energy infrastructures under construction from each other. In addition to this spatial detection, a quarterly time series from July 2016 to June 2021 was derived for all objects. This time series reveals the start of construction, the construction phase and the time of completion with subsequent operation for each object. The derived offshore wind energy infrastructure data set provides the basis for an analysis of the development of the offshore wind energy sector from July 2016 to June 2021. For this analysis, further attributes of the detected offshore wind turbines were derived. The most important of these are the height and installed capacity of a turbine. The turbine height was calculated by a radargrammetric analysis of the previously detected Sentinel-1 signal and then used to statistically model the installed capacity. The results show that in June 2021, 8,885 offshore wind turbines with a total capacity of 40.6 GW were installed worldwide. The largest installed capacities are in the EU (15.2 GW), China (14.1 GW) and the United Kingdom (10.7 GW). From July 2016 to June 2021, China has expanded 13 GW of offshore wind energy infrastructure. The EU has installed 8 GW and the UK 5.8 GW of offshore wind energy infrastructure in the same period. This temporal analysis shows that China was the main driver of the expansion of the offshore wind energy sector in the period under investigation. The derived data set for the description of the offshore wind energy sector was made publicly available. It is thus freely accessible to all decision-makers and stakeholders involved in the development of offshore wind energy projects. Especially in the scientific context, it serves as a database that enables a wide range of investigations. Research questions regarding offshore wind turbines themselves as well as the influence of the expansion in the coming decades can be investigated. This supports the imminent and urgently needed expansion of offshore wind energy in order to promote sustainable expansion in addition to the expansion targets that have been set.},
  language  = {en}
}
@phdthesis{Gruene2022,
  author    = {Gr{\"u}ne, Jeannine},
  title     = {Spin States and Efficiency-Limiting Pathways in Optoelectronic Materials and Devices},
  doi       = {10.25972/OPUS-29340},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293405},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {This thesis addresses the identification and characterization of spin states in optoelectronic materials and devices using multiple spin-sensitive techniques. For this purpose, a systematic study focussing on triplet states as well as associated loss pathways and excited state kinetics was carried out. The research was based on comparing a range of donor:acceptor systems, reaching from organic light emitting diodes (OLEDs) based on thermally activated delayed fluorescence (TADF) to organic photovoltaics (OPV) employing fullerene and multiple non-fullerene acceptors (NFAs). By developing new strategies, e.g., appropriate modeling, new magnetic resonance techniques and experimental frameworks, the influence of spin states in the fundamental processes of organic semiconductors has been investigated. Thereby, the combination of techniques based on the principle of electron paramagnetic resonance (EPR), in particular transient EPR (trEPR) and optically detected magnetic resonance (ODMR), with all-optical methods, such as transient electroluminescence (trEL) and transient absorption (TA), has been employed. As a result, excited spin states, especially molecular and charge transfer (CT) states, were investigated in terms of kinetic behavior and associated pathways, which revealed a significant impact of triplet states on efficiency-limiting processes in both optoelectronic applications.},
  subject      = {Elektronenspinresonanz},
  language  = {en}
}
@phdthesis{Stumpf2022,
  author    = {Stumpf, Pascal},
  title     = {On coverings and reduced residues in combinatorial number theory},
  doi       = {10.25972/OPUS-29350},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293504},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Our starting point is the Jacobsthal function \(j(m)\), defined for each positive integer \(m\) as the smallest number such that every \(j(m)\) consecutive integers contain at least one integer relatively prime to \(m\). It has turned out that improving on upper bounds for \(j(m)\) would also lead to advances in understanding the distribution of prime numbers among arithmetic progressions. If \(P_r\) denotes the product of the first \(r\) prime numbers, then a conjecture of Montgomery states that \(j(P_r)\) can be bounded from above by \(r (\log r)^2\) up to some constant factor. However, the until now very promising sieve methods seem to have reached a limit here, and the main goal of this work is to develop other combinatorial methods in hope of coming a bit closer to prove the conjecture of Montgomery. Alongside, we solve a problem of Recam{\´a}n about the maximum possible length among arithmetic progressions in the least (positive) reduced residue system modulo \(m\). Lastly, we turn towards three additive representation functions as introduced by Erdős, S{\´a}rk{\"o}zy and S{\´o}s who studied their surprising different monotonicity behavior. By an alternative approach, we answer a question of S{\´a}rk{\"o}zy and demostrate that another conjecture does not hold.},
  subject      = {Kombinatorische Zahlentheorie},
  language  = {en}
}
@phdthesis{Hajer2022,
  author    = {Hajer, Jan},
  title     = {Mercury Telluride Nanowires for Topological Quantum Transport},
  doi       = {10.25972/OPUS-29322},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293222},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Novel appraches to the molecular beam epitaxy of core-shell nanowires in the group II telluride material system were explored in this work. Significant advances in growth spurred the development of a flexible and reliable platform for a charge transport characterization of the topological insulator HgTe in a tubular nanowire geometry. The transport results presented provide an important basis for the design of future studies that strive for the experimental realization of topological charge transport in the quantum wire limit.},
  subject      = {Quecksilbertellurid},
  language  = {en}
}
@phdthesis{Reinhart2022,
  author    = {Reinhart, Michael Christian},
  title     = {Enhancing mucosal B cell responses with all-\(trans\) retinoic acid},
  doi       = {10.25972/OPUS-29292},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-292920},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Diarrheal diseases are a major cause of death in developing countries. Vaccinating against the causative pathogens could reduce mortality and morbidity in these countries. Unfortunately, only for some of the most common enteral pathogens are vaccines available. Some of these available vaccines have limitations in terms of effectiveness and duration of protection. There is therefore an urgent need to develop new vaccine strategies that can generate protection against enteral pathogens. The presence of all-trans retinoic acid (ATRA) during lymphocyte maturation is known to imprint a phenotype on lymphocytes that enables them to home to the intestines. Additionally, ATRA is known to play a role in B cell class switch to IgA, which is the dominant immunoglobulin in the intestines. The aim of this study was therefore to investigate whether the addition of all-trans retinoic acid (ATRA) or a retinoic acid receptor agonist (AM80) to a parenteral vaccination could provide protection at the intestinal mucosa against enteric pathogens. C57BL/6 mice received s.c. priming and boosting immunizations with Ovalbumin followed by several s.c. injections with either ATRA, AM80 or the respective solvent as control substance. Feces, serum, saliva and vaginal lavage samples were collected and analyzed by ELISA for detection and relative quantification of antigen-specific antibodies. B cell populations in the draining lymph nodes were investigated after immunization using flow-cytometry. Antigen-specific antibodies producing cells were visualized in the small intestine of vaccinated animals using two-photon microscopy. Animals that were vaccinated and were exposed to AM80, and to a lesser extent ATRA exposed mice, had higher serum, fecal, saliva and vaginal lavage antigen-specific IgA titers when compared to animals that were vaccinated but did not receive ATRA/AM80. Antigen-specific IgG titers were not altered in any of the investigated tissues. In the draining lymph nodes, IgA+ and IgG+ B cells were increased after vaccination and AM80 exposure at several time points within 14 days after vaccination. Antigen-specific IgA+ cells were found in the small intestine of immunized and AM80-exposed but not control substance-exposed mice. These results suggest that the addition of ATRA or AM80 to parenteral vaccine formulations increases the abundance of antigen-specific antibodies at mucosal surfaces, and therefore have the potential to generate protective antibody titers at those mucosal surfaces.},
  subject      = {Impfung},
  language  = {en}
}
@phdthesis{Chithelen2022,
  author    = {Chithelen, Janice},
  title     = {Targeting viral and host factors to optimize anti-measles virus therapy},
  doi       = {10.25972/OPUS-29305},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293059},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Measles is an ancient disease with historical records as early as the 9th century. Extensive study as well as advances in scientific knowledge of virology have led to identification of the viral pathogen and subsequent development of an effective vaccine leading to global efforts towards measles elimination. In 2018, around 140,000 deaths were reported due to measles with incomplete vaccine coverage being one of the leading causes of resurgence. Measles is highly contagious and often regarded as a childhood illness. However, measles is associated with a number of complications and persistent infections like subacute sclerosing panencephalitis (SSPE), which have brought into focus the need for specific anti-viral therapies. The aim of this study was to target host and viral factors to optimize anti-measles virus therapy. Our approach was to test a panel of compounds known to inhibit host cell functions or viral factors for their antiviral effect on measles replication. Primary human lymphocytes, persistently infected NT2 cells and post-mitotic neurons were used as in vitro model systems of acute, persistent and neuronal infection respectively to test the inhibitors. Using the inhibitors Ceranib-2 and SKI-II to target the sphingolipid metabolism enzymes acid ceramidase and sphingosine kinase in infected human primary lymphocytes, we observed a decreased protein translational capacity mediated by mTORC1, EIF4E and ribosomal protein S6 phosphorylation that probably contributes to the antiviral effect. In the persistently infected neural NT2 cells and post-mitotic neurons derived from LUHMES cells, we observed effective infection inhibition and viral clearance upon treatment with a small non-nucleoside inhibitor (ERDRP-0519) specifically targeting the Morbillivirus large polymerase. Other inhibitors such as Ribavirin and Favipiravir were less effective. To conclude, 1) we identified a mTOR associated protein translation axis associated with the sphingolipid metabolism, which affects measles virus replication and 2) In vitro persistently infected neuronal and post-mitotic neuron models were successfully used as a rapid method to test antivirals against measles virus.},
  language  = {en}
}
@phdthesis{Stauffert2022,
  author    = {Stauffert, Jan-Philipp},
  title     = {Temporal Confounding Effects in Virtual and Extended Reality Systems},
  doi       = {10.25972/OPUS-29060},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290609},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Latency is an inherent problem of computing systems. Each computation takes time until the result is available. Virtual reality systems use elaborated computer resources to create virtual experiences. The latency of those systems is often ignored or assumed as small enough to provide a good experience. This cumulative thesis is comprised of published peer reviewed research papers exploring the behaviour and effects of latency. Contrary to the common description of time invariant latency, latency is shown to fluctuate. Few other researchers have looked into this time variant behaviour. This thesis explores time variant latency with a focus on randomly occurring latency spikes. Latency spikes are observed both for small algorithms and as end to end latency in complete virtual reality systems. Most latency measurements gather close to the mean latency with potentially multiple smaller clusters of larger latency values and rare extreme outliers. The latency behaviour differs for different implementations of an algorithm. Operating system schedulers and programming language environments such as garbage collectors contribute to the overall latency behaviour. The thesis demonstrates these influences on the example of different implementations of message passing. The plethora of latency sources result in an unpredictable latency behaviour. Measuring and reporting it in scientific experiments is important. This thesis describes established approaches to measuring latency and proposes an enhanced setup to gather detailed information. The thesis proposes to dissect the measured data with a stacked z-outlier-test to separate the clusters of latency measurements for better reporting. Latency in virtual reality applications can degrade the experience in multiple ways. The thesis focuses on cybersickness as a major detrimental effect. An approach to simulate time variant latency is proposed to make latency available as an independent variable in experiments to understand latency's effects. An experiment with modified latency shows that latency spikes can contribute to cybersickness. A review of related research shows that different time invariant latency behaviour also contributes to cybersickness.},
  subject      = {Virtuelle Realit{\"a}t},
  language  = {en}
}
@phdthesis{Krones2022,
  author    = {Krones, David},
  title     = {The Role of Acid Sphingomyelinase in \(Staphylococcus\) \(aureus\) Infection of Endothelial Cells},
  doi       = {10.25972/OPUS-29049},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290492},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Staphylococcus aureus is a human bacterial pathogen responsible for a variety of diseases including bacterial pneumonia and sepsis. Recent studies provided an explanation, how S. aureus and its exotoxins contribute to the degradation of endothelial junction proteins and damage lung tissue [4]. Previous findings were indicating an involvement of acid sphingomyelinase (ASM) activity in cell barrier degradation [5]. In the presented study the impact of singular virulence factors, such as staphylococcal α-toxin, on in vitro cell barrier integrity as well as their ability to elicit an activation of ASM were investigated. Experiments with bacterial supernatants performed on human endothelial cells demonstrated a rapid dissociation after treatment, whereas murine endothelial cells were rather resistant against cell barrier degradation. Furthermore, amongst all tested staphylococcal toxins it was found that only α-toxin had a significant impact on endothelial junction proteins and ASM activity. Ablation of this single toxin was sufficient to protect endothelial cells from cell barrier degradation and activation of ASM was absent. In this process it was verified, that α-toxin induces a recruitment of intracellular ASM, which is accompanied by rapid and oscillating changes in cytoplasmic Ca2+ concentration and an increased exposure of Lysosomal associated membrane protein 1 (LAMP1) on the cell surface. Recruitment of lysosomal ASM is associated, among other aspects, to plasma membrane repair and was previously described to be involved with distinct pathogens as well as other pore forming toxins (PFT). However, with these findings a novel feature for α-toxin has been revealed, indicating that the staphylococcal PFT is able to elicit a similar process to previously described plasma membrane repair mechanisms. Increased exposure and intake of surface membrane markers questioned the involvement of ASM activity in S. aureus internalization by non-professional phagocytes such as endothelial cells. By modifying ASM expression pattern as well as application of inhibitors it was possible to reduce the intracellular bacterial count. Thus, a direct connection between ASM activity and S. aureus infection mechanisms was observed, therefore this study exemplifies how S. aureus is able to exploit the host cell sphingolipid metabolism as well as benefit of it for invasion into non-professional phagocytic cells},
  subject      = {Staphylococcus aureus},
  language  = {en}
}
@phdthesis{Grob2022,
  author    = {Grob, Robin},
  title     = {The Function of Learning Walks of \({Cataglyphis Ants}\): Behavioral and Neuronal Analyses},
  doi       = {10.25972/OPUS-29017},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290173},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Humans and animals alike use the sun, the moon, and the stars to guide their ways. However, the position of celestial cues changes depending on daytime, season, and place on earth. To use these celestial cues for reliable navigation, the rotation of the sky has to be compensated. While humans invented complicated mechanisms like the Antikythera mechanism to keep track of celestial movements, animals can only rely on their brains. The desert ant Cataglyphis is a prime example of an animal using celestial cues for navigation. Using the sun and the related skylight polarization pattern as a compass, and a step integrator for distance measurements, it can determine a vector always pointing homewards. This mechanism is called path integration. Since the sun's position and, therefore, also the polarization pattern changes throughout the day, Cataglyphis have to correct this movement. If they did not compensate for time, the ants' compass would direct them in different directions in the morning and the evening. Thus, the ants have to learn the solar ephemeris before their far-reaching foraging trips. To do so, Cataglyphis ants perform a well-structured learning-walk behavior during the transition phase from indoor worker to outdoor forager. While walking in small loops around the nest entrance, the ants repeatedly stop their forward movements to perform turns. These can be small walked circles (voltes) or tight turns about the ants' body axes (pirouettes). During pirouettes, the ants gaze back to their nest entrance during stopping phases. These look backs provide a behavioral read-out for the state of the path integrator. The ants "tell" the observer where they think their nest is, by looking back to it. Pirouettes are only performed by Cataglyphis ants inhabiting an environment with a prominent visual panorama. This indicates, that pirouettes are performed to learn the visual panorama. Voltes, on the other hand, might be used for calibrating the celestial compass of the ants. In my doctoral thesis, I employed a wide range of state-of-the-art techniques from different disciplines in biology to gain a deeper understanding of how navigational information is acquired, memorized, used, and calibrated during the transition phase from interior worker to outdoor forager. I could show, that celestial orientation cues that provide the main compass during foraging, do not guide the ants during the look-backbehavior of initial learning walks. Instead Cataglyphis nodus relies on the earth's magnetic field as a compass during this early learning phase. While not guiding the ants during their first walks outside of the nest, excluding the ants from perceiving the natural polarization pattern of the skylight has significant consequences on learning-related plasticity in the ants' brain. Only if the ants are able to perform their learning-walk behavior under a skylight polarization pattern that changes throughout the day, plastic neuronal changes in high-order integration centers are induced. Especially the mushroom bogy collar, a center for learning and memory, and the central complex, a center for orientation and motor control, showed an increase in volume after learning walks. This underlines the importance of learning walks for calibrating the celestial compass. The magnetic compass might provide the necessary stable reference system for the ants to calibrate their celestial compass and learn the position of landmark information. In the ant brain, visual information from the polarization-sensitive ocelli converge in tight apposition with neuronal afferents of the mechanosensitive Johnston's organ in the ant's antennae. This makes the ants' antennae an interesting candidate for studying the sensory bases of compass calibration in Cataglyphis ants. The brain of the desert navigators is well adapted to successfully accomplish their navigational needs. Females (gynes and workers) have voluminous mushroom bodies, and the synaptic complexity to store large amount of view-based navigational information, which they acquire during initial learning walks. The male Cataglyphis brain is better suited for innate behaviors that support finding a mate. The results of my thesis show that the well adapted brain of C. nodus ants undergoes massive structural changes during leaning walks, dependent on a changing celestial polarization pattern. This underlies the essential role of learning walks in the calibration of orientation systems in desert ants.},
  subject      = {Cataglyphis},
  language  = {en}
}
@phdthesis{Vogel2022,
  author    = {Vogel, Cassandra Ezra},
  title     = {The effects of land-use and agroecological practices on biodiversity and ecosystem services in tropical smallholder farms},
  doi       = {10.25972/OPUS-29066},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290661},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Biodiversity is in rapid decline worldwide. These declines are more pronounced in areas that are currently biodiversity rich, but economically poor - essentially describing many tropical regions in the Global South where landscapes are dominated by smallholder agriculture. Agriculture is an important driver of biodiversity decline, through habitat destruction and unsustainable practices. Ironically, agriculture itself is dependent on a range of ecosystem services, such as pollination and pest control, provided by biodiversity. Biodiversity on fields and the delivery of ecosystem services to crops is often closely tied to the composition of the surrounding landscape - complex landscapes with a higher proportion of (semi-)natural habitats tend to support a high abundances and biodiversity of pollinators and natural enemies that are beneficial to crop production. However, past landscape scale studies have focused primarily on industrialized agricultural landscapes in the Global North, and context dependent differences between regions and agricultural systems are understudied. Smallholder agriculture supports 2 billion people worldwide and contributes to over half the world's food supply. Yet smallholders, particularly in sub-Saharan Africa, are underrepresented in research investigating the consequences of landscape change and agricultural practices. Where research in smallholder agriculture is conducted, the focus is often on commodity crops, such as cacao, and less on crops that are directly consumed by smallholder households, though the loss of services to these crops could potentially impact the most vulnerable farmers the hardest. Agroecology - a holistic and nature-based approach to agriculture, provides an alternative to unsustainable input-intensive agriculture. Agroecology has been found to benefit smallholders through improved agronomical and food-security outcomes. Co-benefits of agroecological practices with biodiversity and ecosystem services are assumed, but not often empirically tested. In addition, the local and landscape effects on biodiversity and ecosystem services are more commonly studied in isolation, but their potentially interactive effects are so far little explored. Our study region in northern Malawi exemplifies many challenges experienced by smallholder farmers throughout sub-Saharan Africa and more generally in the Global South. Malawi is located in a global biodiversity hotspot, but biodiversity is threatened by rapid habitat loss and a push for input-intensive agriculture by government and other stakeholders. In contrast, agroecology has been effectively promoted and implemented in the study region. We investigated how land-use differences and the agroecological practices affects biodiversity and ecosystem services of multiple taxa in a maize-bean intercropping system (Chapter 2), and pollination of pumpkin (Chapter 3) and pigeon pea (Chapter 4). Additionally, the effects of local and landscape scale shrub- to farmland habitat conversion was investigated on butterfly communities, as well as the potential for agroecology to mitigate these effects (Chapter 5).},
  language  = {en}
}
@phdthesis{Scharnagl2022,
  author    = {Scharnagl, Julian},
  title     = {Distributed Guidance, Navigation and Control for Satellite Formation Flying Missions},
  isbn      = {978-3-945459-42-3},
  doi       = {10.25972/OPUS-28753},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287530},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Ongoing changes in spaceflight - continuing miniaturization, declining costs of rocket launches and satellite components, and improved satellite computing and control capabilities - are advancing Satellite Formation Flying (SFF) as a research and application area. SFF enables new applications that cannot be realized (or cannot be realized at a reasonable cost) with conventional single-satellite missions. In particular, distributed Earth observation applications such as photogrammetry and tomography or distributed space telescopes require precisely placed and controlled satellites in orbit. Several enabling technologies are required for SFF, such as inter-satellite communication, precise attitude control, and in-orbit maneuverability. However, one of the most important requirements is a reliable distributed Guidance, Navigation and Control (GNC) strategy. This work addresses the issue of distributed GNC for SFF in 3D with a focus on Continuous Low-Thrust (CLT) propulsion satellites (e.g., with electric thrusters) and concentrates on circular low Earth orbits. However, the focus of this work is not only on control theory, but control is considered as part of the system engineering process of typical small satellite missions. Thus, common sensor and actuator systems are analyzed to derive their characteristics and their impacts on formation control. This serves as the basis for the design, implementation, and evaluation of the following control approaches: First, a Model Predictive Control (MPC) method with specific adaptations to SFF and its requirements and constraints; second, a distributed robust controller that combines consensus methods for distributed system control and \$H_{\infty}\$ robust control; and finally, a controller that uses plant inversion for control and combines it with a reference governor to steer the controller to the target on an optimal trajectory considering several constraints. The developed controllers are validated and compared based on extensive software simulations. Realistic 3D formation flight scenarios were taken from the Networked Pico-Satellite Distributed System Control (NetSat) cubesat formation flight mission. The three compared methods show different advantages and disadvantages in the different application scenarios. The distributed robust consensus-based controller for example lacks the ability to limit the maximum thrust, so it is not suitable for satellites with CLT. But both the MPC-based approach and the plant inversionbased controller are suitable for CLT SFF applications, while showing again distinct advantages and disadvantages in different scenarios. The scientific contribution of this work may be summarized as the creation of novel and specific control approaches for the class of CLT SFF applications, which is still lacking methods withstanding the application in real space missions, as well as the scientific evaluation and comparison of the developed methods.},
  subject      = {Kleinsatellit},
  language  = {en}
}
@phdthesis{Uereyen2022,
  author    = {{\"U}reyen, Soner},
  title     = {Multivariate Time Series for the Analysis of Land Surface Dynamics - Evaluating Trends and Drivers of Land Surface Variables for the Indo-Gangetic River Basins},
  doi       = {10.25972/OPUS-29194},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-291941},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The investigation of the Earth system and interplays between its components is of utmost importance to enhance the understanding of the impacts of global climate change on the Earth's land surface. In this context, Earth observation (EO) provides valuable long-term records covering an abundance of land surface variables and, thus, allowing for large-scale analyses to quantify and analyze land surface dynamics across various Earth system components. In view of this, the geographical entity of river basins was identified as particularly suitable for multivariate time series analyses of the land surface, as they naturally cover diverse spheres of the Earth. Many remote sensing missions with different characteristics are available to monitor and characterize the land surface. Yet, only a few spaceborne remote sensing missions enable the generation of spatio-temporally consistent time series with equidistant observations over large areas, such as the MODIS instrument. In order to summarize available remote sensing-based analyses of land surface dynamics in large river basins, a detailed literature review of 287 studies was performed and several research gaps were identified. In this regard, it was found that studies rarely analyzed an entire river basin, but rather focused on study areas at subbasin or regional scale. In addition, it was found that transboundary river basins remained understudied and that studies largely focused on selected riparian countries. Moreover, the analysis of environmental change was generally conducted using a single EO-based land surface variable, whereas a joint exploration of multivariate land surface variables across spheres was found to be rarely performed. To address these research gaps, a methodological framework enabling (1) the preprocessing and harmonization of multi-source time series as well as (2) the statistical analysis of a multivariate feature space was required. For development and testing of a methodological framework that is transferable in space and time, the transboundary river basins Indus, Ganges, Brahmaputra, and Meghna (IGBM) in South Asia were selected as study area, having a size equivalent to around eight times the size of Germany. These basins largely depend on water resources from monsoon rainfall and High Mountain Asia which holds the largest ice mass outside the polar regions. In total, over 1.1 billion people live in this region and in parts largely depend on these water resources which are indispensable for the world's largest connected irrigated croplands and further domestic needs as well. With highly heterogeneous geographical settings, these river basins allow for a detailed analysis of the interplays between multiple spheres, including the anthroposphere, biosphere, cryosphere, hydrosphere, lithosphere, and atmosphere. In this thesis, land surface dynamics over the last two decades (December 2002 - November 2020) were analyzed using EO time series on vegetation condition, surface water area, and snow cover area being based on MODIS imagery, the DLR Global WaterPack and JRC Global Surface Water Layer, as well as the DLR Global SnowPack, respectively. These data were evaluated in combination with further climatic, hydrological, and anthropogenic variables to estimate their influence on the three EO land surface variables. The preprocessing and harmonization of the time series was conducted using the implemented framework. The resulting harmonized feature space was used to quantify and analyze land surface dynamics by means of several statistical time series analysis techniques which were integrated into the framework. In detail, these methods involved (1) the calculation of trends using the Mann-Kendall test in association with the Theil-Sen slope estimator, (2) the estimation of changes in phenological metrics using the Timesat tool, (3) the evaluation of driving variables using the causal discovery approach Peter and Clark Momentary Conditional Independence (PCMCI), and (4) additional correlation tests to analyze the human influence on vegetation condition and surface water area. These analyses were performed at annual and seasonal temporal scale and for diverse spatial units, including grids, river basins and subbasins, land cover and land use classes, as well as elevation-dependent zones. The trend analyses of vegetation condition mostly revealed significant positive trends. Irrigated and rainfed croplands were found to contribute most to these trends. The trend magnitudes were particularly high in arid and semi-arid regions. Considering surface water area, significant positive trends were obtained at annual scale. At grid scale, regional and seasonal clusters with significant negative trends were found as well. Trends for snow cover area mostly remained stable at annual scale, but significant negative trends were observed in parts of the river basins during distinct seasons. Negative trends were also found for the elevation-dependent zones, particularly at high altitudes. Also, retreats in the seasonal duration of snow cover area were found in parts of the river basins. Furthermore, for the first time, the application of the causal discovery algorithm on a multivariate feature space at seasonal temporal scale revealed direct and indirect links between EO land surface variables and respective drivers. In general, vegetation was constrained by water availability, surface water area was largely influenced by river discharge and indirectly by precipitation, and snow cover area was largely controlled by precipitation and temperature with spatial and temporal variations. Additional analyses pointed towards positive human influences on increasing trends in vegetation greenness. The investigation of trends and interplays across spheres provided new and valuable insights into the past state and the evolution of the land surface as well as on relevant climatic and hydrological driving variables. Besides the investigated river basins in South Asia, these findings are of great value also for other river basins and geographical regions.},
  subject      = {Multivariate Analyse},
  language  = {en}
}
@phdthesis{Ochs2022,
  author    = {Ochs, Maximilian Thomas},
  title     = {Electrically Connected Nano-Optical Systems: From Refined Nanoscale Geometries to Selective Molecular Assembly},
  doi       = {10.25972/OPUS-29114},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-291140},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Metallic nano-optical systems allow to confine and guide light at the nanoscale, a fascinating ability which has motivated a wide range of fundamental as well as applied research over the last two decades. While optical antennas provide a link between visible radiation and localized energy, plasmonic waveguides route light in predefined pathways. So far, however, most experimental demonstrations are limited to purely optical excitations, i.e. isolated structures are illuminated by external lasers. Driving such systems electrically and generating light at the nanoscale, would greatly reduce the device footprint and pave the road for integrated optical nanocircuitry. Yet, the light emission mechanism as well as connecting delicate nanostructures to external electrodes pose key challenges and require sophisticated fabrication techniques. This work presents various electrically connected nano-optical systems and outlines a comprehensive production line, thus significantly advancing the state of the art. Importantly, the electrical connection is not just used to generate light, but also offers new strategies for device assembly. In a first example, nanoelectrodes are selectively functionalized with self-assembled monolayers by charging a specific electrode. This allows to tailor the surface properties of nanoscale objects, introducing an additional degree of freedom to the development of metal-organic nanodevices. In addition, the electrical connection enables the bottom-up fabrication of tunnel junctions by feedback-controlled dielectrophoresis. The resulting tunnel barriers are then used to generate light in different nano-optical systems via inelastic electron tunneling. Two structures are discussed in particular: optical Yagi-Uda antennas and plasmonic waveguides. Their refined geometries, accurately fabricated via focused ion beam milling of single-crystalline gold platelets, determine the properties of the emitted light. It is shown experimentally, that Yagi-Uda antennas radiate light in a specific direction with unprecedented directionality, while plasmonic waveguides allow to switch between the excitation of two propagating modes with orthogonal near-field symmetry. The presented devices nicely demonstrate the potential of electrically connected nano-optical systems, and the fabrication scheme including dielectrophoresis as well as site-selective functionalization will inspire more research in the field of nano-optoelectronics. In this context, different future experiments are discussed, ranging from the control of molecular machinery to optical antenna communication.},
  subject      = {Nanooptik},
  language  = {en}
}
@phdthesis{Karageorgos2022,
  author    = {Karageorgos, Panagiotis},
  title     = {Investigating Reading Fluency in German Primary School Children: Interplay of Word Reading Accuracy, Speed, and Prosody},
  doi       = {10.25972/OPUS-29261},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-292612},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Reading skills are among the most important basic skills in society. However, not all readers are able to adequately understand texts or decode individual words. Findings from the Progress in International Reading Literacy Study (PIRLS; German: IGLU) show that about one fifth of fourth graders can only establish coherence at the local level, and in some cases they only have a rudimentary understanding of the text they read (Bremerich-Vos et al., 2017). In addition, these reading deficits persist and have a negative impact on academic and professional success (Jimerson, 1999). Therefore, identifying the causes of these deficits and creating opportunities for interventions at an early stage is an important research objective. The aim of this dissertation was to examine the relationship between the aspects of reading fluency and their influence on reading comprehension. Despite the increasing scientific interest in reading fluency in recent years, a research gap still exists in the relationship between word recognition accuracy and both speed and the relevance of prosodic patterns for reading comprehension. Study 1 investigated whether German fourth graders (N = 826) were required to reach a certain word-recognition accuracy threshold before their word-recognition speed improved. In addition, a sub-sample (n = 170) with a pre-/posttest design was examined to assess the extent that the existing word-recognition accuracy can influence the effects of a syllable-based reading intervention on word-recognition accuracy and word-recognition speed. Results showed that word-recognition speed improved after children achieved a word-recognition accuracy of 71\%. A positive intervention effect was also found on word-recognition accuracy for children who were below the 71\% threshold before the intervention, whereas the intervention effect on word-recognition speed was positive for all children. However, a positive effect on reading comprehension was only found for children who were above the 71\% threshold before the intervention. Study 2 investigated the relationship between word-recognition accuracy threshold and word-recognition speed shown in the first study in a longitudinal design with German students (N = 1,095). Word-recognition accuracy and speed were assessed from the end of Grade 1 to 4, whereas reading comprehension was assessed from the end of Grade 2 to 4. The results showed that the developmental trajectories of word recognition speed and reading comprehension were steeper in children who reached the word-recognition accuracy threshold by the end of the first grade than in children who later reached or had not reached this threshold. In Study 3, recurrence analysis (RQA) was used to extract prosodic patterns from reading recordings of struggling and skilled readers in the second (n = 67) and fourth grade (n = 69) and was used for the classification into struggling and skilled readers. In addition, the classification based on the prosodic patterns from the recurrence quantification analysis was compared with the classification of prosodic features from the manual transcription of the reading recordings. The results showed that second-grade struggling readers have lengthier pauses within or between words and take more time between pauses on average, whereas fourth-grade struggling readers spend more time between recurring stresses and have multiple diverse patterns in pitch and more recurring accents. Although the recurrence analysis had a good goodness of fit and provided additional information about the relationship of prosody with reading comprehension, the model using prosodic features from transcription had a better fit. In summary, the three studies in this dissertation provide four important insights into reading fluency in German. First, a threshold in word-recognition accuracy must be achieved before word-recognition speed improves. Second, the earlier this accuracy level is reached, the greater the gain in word-recognition speed and reading comprehension. Third, the intervention effects of a primary school reading intervention are influenced by the accuracy level. Fourth, although incorrect pauses within or between words play an important role in identifying and describing struggling readers in second grade, the importance of prosodic patterns increases in fourth grade.},
  subject      = {Worterkennung},
  language  = {en}
}
@phdthesis{Wendel2022,
  author    = {Wendel, Christoph},
  title     = {Spectral Imprints from Electromagnetic Cascades in Blazar Jets},
  doi       = {10.25972/OPUS-29007},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290076},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The extragalactic gamma-ray sky is dominated by blazars, active galactic nuclei (AGN) with a relativistic jet that is closely aligned with the line of sight. Galaxies develop an active nucleus if the central supermassive black hole (BH) accretes large amounts of ambient matter and magnetic flux. The inflowing mass accumulates around the plane perpendicular to the accretion flow's angular momentum. The flow is heated through viscous friction and part of the released energy is radiated as blackbody or non-thermal radiation, with luminosities that can dominate the accumulated stellar luminosity of the host galaxy. A fraction of the accretion flow luminosity is reprocessed in a surrounding field of ionised gas clouds. These clouds, revolving around the central BH, emit Doppler-broadened atomic emission lines. The region where these broad-line-emitting clouds are located is called broad-line region (BLR). About one in ten AGN forms an outflow of radiation and relativistic particles, called a relativistic jet. According to the Blandford-Znajek mechanism, this is facilitated through electromagnetic processes in the magnetosphere of a spinning BH. The latter induces a magnetospheric poloidal current circuit, generating a decelerating torque on the BH and inducing a toroidal magnetic field. Consequently, rotational energy of the BH is converted to Poynting flux streaming away mainly along the rotational axis and starting the jet. One possibility for particle acceleration near the jet base is realised by magnetospheric vacuum gaps, regions temporarily devoid of plasma, such that an intermittent electric field arises parallel to the magnetic field lines, enabling particle acceleration and contributing to the mass loading of the jets. Magnetised structures, containing bunches of relativistic electrons, propagate away from the galactic nucleus along the jets. Assuming that these electrons emit synchrotron radiation and that they inverse-Compton (IC) up-scatter abundant target photons, which can either be the synchrotron photons themselves or photons from external emitters, the emitted spectrum can be theoretically determined. Additionally taking into account that these emission regions move relativistically themselves and that the emission is Doppler-boosted and beamed in forward direction, the typical two-hump spectral energy distribution (SED) of blazars is recovered. There are however findings that challenge this well-established model. Short-time variability, reaching down to minute scales at very high energy gamma rays, is today known to be a widespread phenomenon of blazars, calling for very compact emission regions. In most models of such optically thick emission regions, the gamma-ray flux is usually pair-absorbed exponentially, without considering the cascade evolving from the pair-produced electrons. From the observed flux, it is often concluded that emission emanates from larger distances where the region is optically thin, especially from outside of the BLR. Only in few blazars gamma-ray attenuation associated with pair absorption in the BLR was clearly reported. With the advent of sophisticated high-energy or very high energy gamma-ray detectors, like the Fermi Large Area Telescope or the Major Atmospheric Gamma-ray Imaging Cherenkov telescopes, besides the extraordinarily fast variability spectral features have been found that cannot be explained by conventional models reproducing the two-hump SED. Two such narrow spectral features are discussed in this work. For the nearby blazar Markarian 501, hints to a sharp peak around 3 TeV have been reported from a multi-wavelength campaign carried out in July 2014, while for 3C 279 a spectral dip was found in 2018 data, that can hardly be described with conventional fitting functions. In this work it is examined whether these spectral peculiarities of blazar jet emission can be explained, if the full radiation reprocessing through an IC pair cascade is accounted for. Such a cascade is the multiple concatenation of IC scattering events and pair production events. In the cascades generally considered in this work, relativistic electrons and high-energy photons are injected into a fixed soft target photon field. A mathematical description for linear IC pair cascades with escape terms is delivered on the basis of preliminary works. The steady-state kinetic equations for the electrons and for the photons are determined, whereby it is paid attention to an explicit formulation and to motivating the correct integration borders of all integrals from kinematic constraints. In determining the potentially observable gamma-ray flux, both the attenuated injected flux and the flux evolving as an effect of IC up-scattering, pair absorption and escape are incorporated, giving the emerging spectra very distinct imprints. Much effort is dedicated to the numerical solution of the electrons' kinetic equation via iterative schemes. It is explained why pointwise iteration from higher to lower Lorentz factors is more efficient than iterating the whole set of sampling points. The algorithm is parallelised at two positions. First, several workers can perform pointwise iterations simultaneously. Second, the most demanding integral is cut into a number of part integrals which can be determined by multiple workers. Through these measures, the Python code can be readily applied to simulate steady-state IC pair cascades with escape. In the case of Markarian 501 the developed framework is as follows. The AGN hosts an advection-dominated accretion flow with a normalised accretion rate of several \(10^{-4}\) and an electron temperature near \(10^{10}\) K. On the one hand, the accretion flow illuminates the few ambient gas clouds with approximate radius \(10^{11}\) m, which reprocess a fraction 0.01 of the luminosity into hydrogen and helium emission lines. On the other hand, the gamma rays from the accretion flow create electrons and positrons in a sporadically active vacuum gap in the BH magnetosphere. In the active gap, a power of roughly 0.001 of the Blandford-Znajek power is extracted from the rotating BH through a gap potential drop of several \(10^{18}\) V, generating ultra-relativistic electrons, which subsequently are multiplied by a factor of about \(10^6\) through interaction with the accretion flow photons. This electron beam propagates away from the central engine and encounters the photon field of one passing ionised cloud. The resulting IC pair cascade is simulated and the evolving gamma-ray spectrum is determined. Just above the absorption troughs due to the hydrogen lines, the spectrum exhibits a narrow bump around 3 TeV. When the cascaded emission is added to the emission generated at larger distances, the observed multi-wavelength SED including the sharp peak at 3 TeV is reproduced, underlining that radiation processes beyond conventional models are motivated by distinct spectral features. The dip in the spectrum of 3C 279 is addressed by a similar cascade model. Three types of injection are considered, varying in the ratio of the photon density to the electron density and varying in the spectral shape. The IC pair cascade is assumed to happen either in the dense BLR photon field with a luminosity of several \(10^{37}\) W and a radial size of few \(10^{14}\) m or in the diluted photon field outside of the BLR. The latter scenario is however rejected as the spectral slope around several 100 MeV and the dip at few 10 GeV cannot be reconciled within this model. The radiation cascaded in the BLR can explain the observational data, irrespective of the assumed injected rate. It is therefore concluded that for this period of gamma-ray emission, the radiation production happens at the edge of the BLR of 3C 279. Both investigations show that IC pair cascades can account for fine structure seen in blazar SEDs. It is insufficient to restrict the radiation transport to pure exponential absorption of an injection term. Pair production and IC up-scattering by all generations of photons and electrons in the optically thick regime critically shape the emerging spectra. As the advent of future improved detectors will provide more high-precision spectra, further observations of narrow spectral features can be expected. It seems therefore recommendable to incorporate cascading into conventional radiation production models or to extend the model developed in this work by synchrotron radiation.},
  subject      = {Active galactic nucleus},
  language  = {en}
}
@phdthesis{Anwar2022,
  author    = {Anwar, Ammarah},
  title     = {Natural variation of gene regulatory networks in \(Arabidopsis\) \(thaliana\)},
  doi       = {10.25972/OPUS-29154},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-291549},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Understanding the causal relationship between genotype and phenotype is a major objective in biology. The main interest is in understanding trait architecture and identifying loci contributing to the respective traits. Genome-wide association mapping (GWAS) is one tool to elucidate these relationships and has been successfully used in many different species. However, most studies concentrate on marginal marker effects and ignore epistatic and gene-environment interactions. These interactions are problematic to account for, but are likely to make major contributions to many phenotypes that are not regulated by independent genetic effects, but by more sophisticated gene-regulatory networks. Further complication arises from the fact that these networks vary in different natural accessions. However, understanding the differences of gene regulatory networks and gene-gene interactions is crucial to conceive trait architecture and predict phenotypes. The basic subject of this study - using data from the Arabidopsis 1001 Genomes Project - is the analysis of pre-mature stop codons. These have been incurred in nearly one-third of the ~ 30k genes. A gene-gene interaction network of the co-occurrence of stop codons has been built and the over and under representation of different pairs has been statistically analyzed. To further classify the significant over and under- represented gene-gene interactions in terms of molecular function of the encoded proteins, gene ontology terms (GO-SLIM) have been applied. Furthermore, co- expression analysis specifies gene clusters that co-occur over different genetic and phenotypic backgrounds. To link these patterns to evolutionary constrains, spatial location of the respective alleles have been analyzed as well. The latter shows clear patterns for certain gene pairs that indicate differential selection.},
  subject      = {Arabidopsis thaliana},
  language  = {en}
}
@phdthesis{Schmitt2022,
  author    = {Schmitt, Fabian Bernhard},
  title     = {Transport properties of the three-dimensional topological insulator mercury telluride},
  doi       = {10.25972/OPUS-29173},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-291731},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The subject of this thesis is the investigation of the transport properties of topological and massive surface states in the three-dimensional topological insulator Hg(Mn)Te. These surface states give rise to a variety of extraordinary transport phenomena, making this material system of great interest for research and technological applications. In this connection, many physical properties of the topological insulator Hg(Mn)Te still require in-depth exploration. The overall aim of this thesis is to analyze the quantum transport of HgTe-based devices ranging from hundreds of micrometers (macroscopic) down to a few micrometers in size (microscopic) in order to extend the overall understanding of surface states and the possibilities of their manipulation. In order to exploit the full potential of our high-quality heterostructures, it was necessary to revise and improve the existing lithographic fabrication process of macroscopic three-dimensional Hg(Mn)Te samples. A novel lithographic standard recipe for the fabrication of the HgTe-based macrostructures was developed. This recipe includes the use of an optimized Hall bar design and wet etching instead of etching with high-energy \(\mathrm{{Ar^{+}}}\)-ions, which can damage the samples. Further, a hafnium oxide insulator is applied replacing the SiO\(_{2}\)/Si\(_{3}\)N\(_{4}\) dielectric in order to reduce thermal load. Moreover, the devices are metallized under an alternating angle to avoid discontinuities of the metal layers over the mesa edges. It was revealed that the application of gate-dielectric and top-gate metals results in n-type doping of the devices. This phenomenon could be attributed to quasi-free electrons tunneling from the trap states, which form at the interface cap layer/insulator, through the cap into the active layer. This finding led to the development of a new procedure to characterize wafer materials. It was found that the optimized lithographic processing steps do not unintentionally react chemically with our heterostructures, thus avoiding a degradation of the quality of the Hg(Mn)Te layer. The implementation of new contact structures Ti/Au, In/Ti/Au, and Al/Ti/Au did not result in any improvement compared to the standard structure AuGe/Au. However, a novel sample recipe could be developed, resulting in an intermixing of the contact metals (AuGe and Au) and fingering of metal into the mesa. The extent of the quality of the ohmic contacts obtained through this process has yet to be fully established. This thesis further deals with the lithographic realization of three-dimensional HgTe-based microstructures measuring only a few micrometer in size. Thus, these structures are in the order of the mean free path and the spin relaxation length of topological surface state electrons. A lithographic process was developed enabling the fabrication of nearly any desired microscopic device structure. In this context, two techniques suitable for etching microscopic samples were realized, namely wet etching and the newly established inductively coupled plasma etching. While wet etching was found to preserve the crystal quality of the active layer best, inductively coupled plasma etching is characterized by high reproducibility and excellent structural fidelity. Hence, the etching technique employed depends on the envisaged type of experiment. Magneto-transport measurements were carried out on the macroscopic HgTe-based devices fabricated by means of improved lithographic processing with respect to the transport properties of topological and massive surface states. It was revealed that due to the low charge carrier density present in the leads to the ohmic contacts, these regions can exhibit an insulating behavior at high magnetic fields and extremely low temperatures. As soon as the filling factor of the lowest Landau levels dropped below a critical value (\(\nu_{\mathrm{{c}}}\approx0.8\)), the conductance of the leads decreased significantly. It was demonstrated that the carrier density in the leads can be increased by the growth of modulation doping layers, a back-gate-electrode, light-emitting diode illumination, and by the application of an overlapping top-gate layout. This overlapping top-gate and a back-gate made it possible to manipulate the carrier density of the surface states on both sides of the Hg(Mn)Te layer independently. With this setup, it was identified that topological and massive surface states contribute to transport simultaneously in 3D Hg(Mn)Te. A model could be developed allowing the charge carrier systems populated in the sample to be determined unambiguously. Based on this model, the process of the re-entrant quantum Hall effect observed for the first time in three-dimensional topological insulators could be explained by an interplay of n-type topological and p-type massive surface states. A well-pronounced \(\nu=-1\rightarrow\nu=-2\rightarrow\nu=-1\) sequence of quantum Hall plateaus was found in manganese-doped HgTe-based samples. It is postulated that this is the condensed-matter realization of the parity anomaly in three-dimensional topological insulators. The actual nature of this phenomenon can be the subject of further research. In addition, the measurements have shown that inter-scattering occurs between counter-propagating quantum Hall edge states. The good quantization of the Hall conductance despite this inter-scattering indicates that only the unpaired edge states determine the transport properties of the system as a whole. The underlying inter-scattering mechanism is the topic of a publication in preparation. Furthermore, three-dimensional HgTe-based microstructures shaped like the capital letter "H" were investigated regarding spin transport phenomena. The non-local voltage signals occurring in the measurements could be attributed to a current-induced spin polarization of the topological surface states due to electrons obeying spin-momentum locking. It was shown that the strength of this non-local signal is directly connected to the magnitude of the spin polarization and can be manipulated by the applied top-gate voltage. It was found that in these microstructures, the massive surface and bulk states, unlike the topological surface states, cannot contribute to this spin-associated phenomenon. On the contrary, it was demonstrated that the population of massive states results in a reduction of the spin polarization, either due to the possible inter-scattering of massive and topological surface states or due to the addition of an unpolarized electron background. The evidence of spin transport controllable by a top-gate-electrode makes the three-dimensional material system mercury telluride a promising candidate for further research in the field of spintronics.},
  subject      = {Topologischer Isolator},
  language  = {en}
}
@phdthesis{Trappe2022,
  author    = {Trappe, Julian},
  title     = {The influence of medieval building activity on relief development within the Spessart uplands, Germany. A sedimentological, geophysical and GIS-based approach at different castle and mining sites},
  edition   = {1. Auflage},
  publisher = {W{\"u}rzburg University Press},
  address   = {W{\"u}rzburg},
  isbn      = {978-3-95826-184-6},
  issn      = {0510-9833},
  doi       = {10.25972/WUP-978-3-95826-185-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261499},
  school      = {W{\"u}rzburg University Press},
  pages     = {XXI, 250},
  year      = {2022},
  abstract  = {In the Spessart, a low mountain range in central Germany, a feud during the Middle Ages led to the construction of numerous castles in this region. This study analyzes the mutual influence of (paleo-)relief development and medieval building activity using a geomorphological and geoarchaeological multimethod approach to expand the knowledge of human-environmental interactions during this time. For this purpose, GIS-based terrain analysis and geophysical measurements were conducted and combined with sedimentological information to create 1D-3D models of the subsurface and to assess knowledge of the landscape and relief evolution at various medieval castle and mining sites. The interpretation of all these data led to the answering of numerous site-specific questions on various geomorphological, geoarchaeological, geologic, and archaeological topics that have been explored in this work and have greatly increased our knowledge of each study site. In addition to these key contributions to the archaeological and geomorphological interpretation of individual study sites, a quantification of the anthropogenic influence on the relief development was conducted, a generalized model of the influence was derived, and new methodological and interpretative approaches were developed. Overall, this study links geomorphological/geological and (geo-)archaeological investigations at five medieval sites and delivers important information on human-environmental interactions within the Spessart and beyond.},
  subject      = {Geoarch{\"a}ologie},
  language  = {en}
}
@phdthesis{Kurz2022,
  author    = {Kurz, Hendrikje},
  title     = {Regulation of ion conductance and cAMP/cGMP concentration in megakaryocytes by light},
  doi       = {10.25972/OPUS-21694},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216947},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Platelets play an essential role in haemostasis. Through granule secretion of second wave mediators and aggregation, they secure vascular integrity. Due to incorrect activation, platelet aggregation and subsequent thrombus formation can cause blood vessel occlusion, leading to ischemia. Patients with defects in platelet production have a low platelet count (thrombocytopenia), which can cause an increased bleeding risk. In vitro platelet generation is still in its development phase. So far, no convincing results have been obtained. For this reason, the health care system still depends on blood donors. Platelets are produced by bone marrow megakaryocytes (MKs), which extend long cytoplasmic protrusions, designated proplatelets, into sinusoidal blood vessels. Due to shear forces, platelets are then released into the bloodstream. The molecular mechanisms underlying platelet production are still not fully understood. However, a more detailed insight of this biological process is necessary to improve the in vitro generation of platelets and to optimise treatment regimens of patients. Optogenetics is defined as "light-modulation of cellular activity or of animal behaviour by gene transfer of photo-sensitive proteins". Optogenetics has had a big impact on neuroscience over the last decade. The use of channelrhodopsin 2 (ChR2), a light-sensitive cation channel, made it possible to stimulate neurons precisely and minimally invasive for the first time. Recent developments in the field of optogenetics intend to address a broader scope of cellular and molecular biology. The aim of this thesis is to establish optogenetics in the field of MK research in order to precisely control and manipulate MK differentiation. An existing "optogenetic toolbox" was used, which made it possible to light-modulate the cellular concentration of specific signalling molecules and ion conductance in MKs. Expression of the bacterial photoactivated adenylyl cyclase (bPAC) resulted in a significant increase in cAMP concentration after 5 minutes of illumination. Similarly, intracellular cGMP concentrations in MKs expressing photoactivated guanylyl cyclase (BeCyclop) were elevated. Furthermore, proplatelet formation of MKs expressing the light-sensitive ion channels ChR2 and anion channelrhodopsin (ACR) was altered in a light-dependent manner. These results show that MK physiology can be modified by optogenetic approaches. This might help shed new light on the underlying mechanisms of thrombopoiesis.},
  subject      = {Optogenetik},
  language  = {en}
}
@phdthesis{Heib2022,
  author    = {Heib, Tobias},
  title     = {The role of Rho GTPases in megakaryopoiesis and thrombopoiesis},
  doi       = {10.25972/OPUS-21664},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216645},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Platelets, derived from megakaryocytes (MKs) in the bone marrow (BM), are small, anucleated cells that circulate in the bloodstream and are critical for thrombosis and hemostasis. Megakaryo- and subsequent thrombopoiesis are highly orchestrated processes involving the differentiation and maturation of MKs from hematopoietic stem cells (HSCs), after which MKs are able to release platelets into the bloodstream, a process termed proplatelet formation (PPF). Here, the MK penetrates the endothelial lining and releases cytoplasmic portions (proplatelets) into the blood stream, which finally mature into platelets within the ciruculation. PPF requires an extensive crosstalk as well as a tight regulation of the MK cytoskeleton, in which small GTPases of the Rho family, such as RhoA and Cdc42 are critically involved and play opposing roles. MK and platelet specific Cdc42 or RhoA-deficiency in mice results in macrothrombocytopenia. Moreover, RhoA deficient mice displayed a frequent mislocalization of entire MKs into BM sinusoids, a finding that was reverted upon concomitant lack of Cdc42 but accompanied by an aggravated macrothrombocytopenia. Whether receptors are involved in the process of transendothelial MK migration, however, remained unclear. In the first part of this thesis, a centrifugation-based method ('spin isolation') to harvest murine BM cells was established, which not only reduces experimental time, costs and animals but is also highly suitable for studies on primary and in vitro cultured BM-derived cells. The spin isolation was used particularly for MK studies during the course of the thesis. In the second part of this thesis, a MK- and platelet-specific RhoA/Cdc42 double-deficiency was shown to result in reduced expression of a variety of MK-specific glycoproteins and cytoskeletal regulators of importance during MK maturation and PPF, a phenotype culminating in virtually abolished platelet biogenesis. We thus uncovered that RhoA/Cdc42-regulated gene expression is a prerequisite for cytoplasmic MK maturation, but dispensable for endomitosis. In the third part of this thesis we analyzed mice double-deficient in RhoA and prominent MK receptors which are potentially involved in the regulation of PPF in the BM environment. We were able to show that integrins as well as the inhibitory receptor G6b-B are dispensable for transendothelial migration of RhoA-deficient MKs. Surprisingly however, the myelofibrosis and concomitant osteosclerosis observed in G6b-B single-deficient mice was attenuated in RhoA/G6b B double-deficient mice, thus implying an important role of RhoA during myelofibrotic disease progression. BM transplantation experiments furthermore revealed that not only the macrothrombocytopenia but also the transmigration of RhoA-deficient MKs is due to cell-intrinsic defects and not related to possible Pf4-Cre off-target effects in non-hematopoietic cells. In the last part of this study we demonstrated that the new approach for MK- and platelet-specific gene ablatation using Gp1ba-Cre deleter mice is associated with intrinsic MK defects and in addition results in insufficient depletion of RhoA compared to the Pf4-Cre model, positioning the latter still as the gold standard for studying MK biology.},
  subject      = {Megakaryozyt},
  language  = {en}
}
@phdthesis{Hagspiel2022,
  author    = {Hagspiel, Stephan Alexander},
  title     = {Synthesis and Reactivity of Pseudohalide-substituted Boranes and Borylenes},
  doi       = {10.25972/OPUS-24945},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249459},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {This work involves the synthesis and reactivity of pseudohalide-substituted boranes and borylenes. A series of compounds of the type (CAAC)BR2Y (CAAC = cyclic alkyl(amino)carbene; R = H, Br; Y = CN, NCS, PCO) were prepared first. The two-electron reduction of (CAAC)BBr2Y (Y = CN, NCS) in the presence of a second Lewis base L (L = N-heterocyclic carbene) resulted in the formation of the corresponding doubly Lewis base-stabilized pseudohaloborylenes (CAAC)(L)BY. These borylenes show versatile reactivity patterns, including their oxidation to the corresponding radical cations, coordination via the respective pseudohalide substituent to group 6 metal carbonyl complexes, as well as a boron-centered protonation with Br{\o}nsted acids to boronium cations. Reduction of (CAAC)BBr2(NCS) in the absence of a second donor ligand, led to the formation of boron-doped thiazolothiazoles via reductive dimerization of two isothiocyanatoborylenes. These B,N,S-heterocycles possess a low degree of aromaticity as well as interesting photophysical properties and can furthermore be protonated as well as hydroborated. Additionally, CAAC adducts of the parent boraphosphaketene (CAAC)BH2(PCO) could be prepared, which readily reacted with boroles [Ph4BR'] (R' = aryl) via decarbonylation in a ring expansion reaction. The obtained 1,2-phosphaborinines represent B,P-isosteres of benzene and consequently could be coordinated to metal carbonyl complexes of the chromium triade via η6-coordination, resulting in new half-sandwich complexes thereof.},
  subject      = {Borylene},
  language  = {en}
}
@phdthesis{Gross2022,
  author    = {Gross, Carina},
  title     = {The role of platelets in hepatic ischemia reperfusion injury in mice},
  doi       = {10.25972/OPUS-21618},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216180},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Platelets are the second most abundant blood cells and their main function is maintenance of vascular integrity. In addition, platelets are increasingly recognized as cells with immune functions, as they participate in the recruitment of immune cells and modulate the progression and severity of an immune response. So-called lipid mediators, which are - besides other cells - released by activated platelets, influence the immune response. LTB4 is one of these potent lipid mediators and is able to activate neutrophils and induce their infiltration into injured tissue. In order to investigate the involvement of platelets in inflammatory processes, a murine model of hepatic ischemia reperfusion injury as well as confocal intravital microscopy of the liver were established. Both methods were used to analyze the influence of platelets on the inflammation that follows sterile liver inflammation. We found platelet function to be unaltered after three hours of reperfusion and platelet aggregation to be irrelevant for the outcome of hepatic ischemia reperfusion injury. However, a strong impact of the GPIb-vWF axis could be observed, as antibody mediated blockade of GPIb as well as vWF-deficiency significantly reduced liver damage markers and decreased neutrophil infiltration. GPIb-IL-4R mice were used to exclude the possibility that the protective effects of the anti-GPIbα antibody treatment (p0p/B) results from something else than blocking GPIbα. Furthermore, the slope of neutrophil infiltration was decreased in p0p/B-treated mice, leading to overall decreased neutrophil numbers in the liver after three hours of reperfusion. Blockade of the integrin αIIbβ3, however, showed no reduction in neutrophil infiltration into the post-ischemic liver, in line with unaltered liver damage. To study the role of leukotriene B4, conditional and constitutive knockout mice for the LTA4 hydrolase, which catalyzes the last step in LTB4 synthesis, were generated. Lta4h deficiency did not affect general platelet functionality in hemostasis and thrombosis. Interestingly, Lta4h-/- mice were not protected from cellular damage following hepatic ischemia, despite lower neutrophil numbers in the post-ischemic liver. Intravital microscopy of the pancreas was established and revealed increased CD4+ T cell numbers in GPVI-deficient animals compared to WT controls in line with the pre-diabetic phenotype of Gp6-/- mice that was revealed in Grzegorz Sumara's group. Furthermore, platelet 'behavior' in pancreatic islets was observed following glucose injection. We found a high number of platelets adherent to islet sinusoids under basal conditions and no rolling/decelerating of platelets following glucose injection. This was accompanied by temporary sinusoidal constriction and stop of the blood flow. This phenomenon was not observed in control settings (injection of PBS, insulin or L-glucose). In a side project, which was carried out jointly with Tobias Heib, a side by side comparison of the classical syringe-based flushing and the centrifugation-based spinning method to isolate murine bone marrow was conducted. Flow cytometry revealed no differences in the distribution of hematopoietic stem cells and immune cells and functional analysis with primary and cultured megakaryocytes (MKs) showed comparable results in all conducted assays. Thus, our data demonstrated that the faster and more efficient spinning method can be used for the isolation of bone marrow cells.},
  language  = {en}
}
@phdthesis{Philipp2022,
  author    = {Philipp, Michael Stephan Maria},
  title     = {N-Heterocyclic Carbenes and Cyclic (Alkyl)(amino)carbenes as Ligands for p-Block Element Compounds},
  doi       = {10.25972/OPUS-28929},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-289295},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In der vorliegenden Arbeit wird die Synthese und Reaktivit{\"a}t neuer NHC- und cAAC-stabilisierter Lewis-S{\"a}ure/Lewis-Base-Addukte von Verbindungen mit Elementen der Gruppen 14 und 15 beschrieben.},
  subject      = {Lewis-Addukt},
  language  = {en}
}
@phdthesis{Greving2022,
  author    = {Greving, Sven},
  title     = {Desirable Difficulties in Applied Learning Settings: Mechanisms and Effects},
  doi       = {10.25972/OPUS-28884},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288848},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Improving retention of learned content by means of a practice test is a learning strategy that has been researched since a century and has been consistently found to be more effective than comparable learning strategies such as restudy (i.e., the testing effect). Most importantly, practicing test questions has been found to outperform restudy even when no additional information about the correct answers was provided to practice test takers, rendering practice tests effective and efficient in fostering retention of learning content. Since 15 years, additional scientific attention is devoted to this memory phenomenon and additional research investigated to what extend practicing test questions is relevant in real-world educational settings. This dissertation first presents the evidence for testing effects in applied educational settings by presenting key publications and presenting findings from a methodological review conducted for this purpose. Within this dissertation, theories are presented why practicing test questions should benefit learning in real-world educational settings even without the provision of additional information and key variables for the effectiveness of practicing test questions are presented. Four studies presented in this dissertation aimed at exploring these assumptions in actual university classrooms while also trying to implement new methods of practicing learning content and thus augment course procedures. Findings from these studies—although not often consistent—will be incorporated and interpreted in the light of the theoretical accounts on the testing effect. The main conclusion that can be drawn from this dissertation is that, given the right circumstances, practicing test questions can elicit beneficial effects on the retention of learning content that are independent of additional information and thus taking a practice test per se, can foster retention of real-world learning content.},
  subject      = {Unterrichtspsychologie},
  language  = {en}
}
@phdthesis{Wertgen2022,
  author    = {Wertgen, Andreas Gabriel},
  title     = {The Role of Source Credibility in the Validation of Text Information},
  doi       = {10.25972/OPUS-28861},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288619},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Numerous experiments have shown that an evaluative and passive process, known as validation, accompanies activation and integration, which are fundamental processes of text comprehension. During the construction of a mental model, validation implicitly assesses the plausibility of incoming information by checking its consistency with world knowledge, prior beliefs, and contextual information (e.g., the broader discourse context). However, research on potential influences that shape validation processes has just started. One branch of research is investigating how world knowledge and contextual information contribute to integration and validation. World knowledge usually influences validation more strongly because information plausibility is the primary criterion for validation, but strong contextual information can yield influences as well. Contextual information that may be specifically relevant for routine validation is the credibility of a source providing text information. Source credibility bears a strong conceptual relationship to the validity of information. However, a dearth of research has investigated joint effects of plausibility and source credibility for routine validation. To fill this research gap, the aim of the present dissertation was to examine the role of source credibility in routine validation processes of text information. This dissertation argues that both source credibility and plausibility are considered in these processes. In particular, information plausibility is proposed as the primary criterion, but source credibility may modulate validation as an additional criterion. To this end, three studies with five self-paced reading experiments were conducted in which reading times served as an implicit indicator of validation and plausibility judgments as an explicit indicator, and the convergence or divergence between the two indicators was interpreted. The first study examined the interplay of plausibility and source credibility for the validation of world-knowledge consistent versus inconsistent text information embedded in short narratives. This highly plausible or highly implausible information was provided by a high- or low-expertise source. In Study 1, plausibility dominated validation as suggested by faster reading times and higher plausibility judgments for world-knowledge consistent information. Importantly, source credibility modulated the validation of highly implausible information but seemed to not matter for plausible information. High-credible sources increased the implausibility of highly implausible information to a greater extent compared with low-credible sources as indicated by longer reading times and lower plausibility judgments. These results diverged from recent findings from Foy et al. (2017). The second study investigated whether the modulating role of source credibility depends on the degree of implausibility of an information. Thus, Study 2 extended Study 1 by an intermediate, somewhat implausible level of plausibility (comparable to the implausible claims in Foy et al., 2017). Similar to Study 1, plausibility dominated validation as indicated by lower reading times and plausibility judgments with higher world-knowledge inconsistency. Again, source credibility had no effect on the routine validation of plausible information. However, high-credible sources mitigated the implausibility of somewhat implausible information as indicated by faster reading times and higher plausibility judgments but exacerbated the implausibility of highly implausible information as indicated by slower reading times and lower plausibility judgments. In short, Study 2 findings not only integrates the seemingly divergent results of Study 1 and Foy et al. (2017) but also provides strong support for the assumption that the degree of implausibility determines the modulating role of source credibility for validation. The third study examined the relationship of source credibility and plausibility in an ecologically valid social media setting with short Twitter messages varying in world-knowledge and text-belief consistency by trustworthy and untrustworthy sources. In sum, plausibility and to a lesser extent source credibility mattered for routine validation and explicit evaluation of text information as indicated by reading times and plausibility judgments. However, the pattern partly diverged from Study 1 and 2, possibly because the source information was more salient. In sum, the present dissertation yielded three insights. First, the findings further extends evidence for routine validation based on world-knowledge and prior beliefs. Second, the studies suggest that source credibility can modulate validation. Readers used source credibility cues for routine validation and the explicit evaluation of text information in all studies. Third, the impact of source credibility seems to depend on the degree of implausibility of information. The present findings have theoretical implications for theories of validation and text comprehension as well as practical implications for targeting threats associated with the prevalence of inaccurate information, for example, on the World Wide Web. Future research using eye-tracking methodology could further disentangle the routine and strategic underlying processes of the relationship between source credibility and plausibility.},
  subject      = {Textverstehen},
  language  = {en}
}
@phdthesis{Vogel2022,
  author    = {Vogel, Sebastian},
  title     = {Determinants of saproxylic biodiversity and conclusions for conservation},
  doi       = {10.25972/OPUS-28926},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-289266},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Over the past centuries, anthropogenic utilization has fundamentally changed the appearance of European forest ecosystems. Constantly growing and changing demands have led to an enormous decline in ecological key elements and a structural homogenization of most forests. These changes have been accompanied by widespread declines of many forest-dwelling and especially saproxylic, i.e. species depending on deadwood. In order to counteract this development, various conservation strategies have been developed, but they primarily focus on a quantitative deadwood enrichment. However, the diversity of saproxylic species is furthermore driven by a variety of abiotic and biotic determinants as well as interactions between organisms. A detailed understanding of these processes has so far been largely lacking. The aim of the present thesis was therefore to improve the existing ecological knowledge of determinants influencing saproxylic species and species communities in order to provide the basis for evidence-based and adapted conservation measures. In chapter II of this thesis, I first investigated the impact of sun exposure, tree species, and their combination on saproxylic beetles, wood-inhabiting fungi, and spiders. Therefore, logs and branches of six tree species were set up under different sun exposures in an experimental approach. The impact of sun exposure and tree species strongly differed among single saproxylic taxa as well as diameters of deadwood. All investigated taxa were affected by sun exposure, whereby sun exposure resulted in a higher alpha-diversity of taxa recorded in logs and a lower alpha-diversity of saproxylic beetles reared from branches compared to shading by canopy. Saproxylic beetles and wood-inhabiting fungi as obligate saproxylic species were additionally affected by tree species. In logs, the respective impact of both determinants also resulted in divergent community compositions. Finally, a rarefaction/extrapolation method was used to evaluate the effectiveness of different combinations of tree species and sun exposure for the conservation of saproxylic species diversity. Based on this procedure, a combination of broadleaved and coniferous as well as hard- and softwood tree species was identified to support preferably high levels of saproxylic species diversity. The aim of chapter III was to evaluate the individual conservational importance of tree species for the protection of saproxylic beetles. For this, the list of tree species sampled for saproxylic beetles was increased to 42 different tree species. The considered tree species represented large parts of taxonomic and phylogenetic diversity native to Central Europe as well as the most important non-native tree species of silvicultural interest. Freshly cut branches were set up for one year and saproxylic beetles were reared afterwards for two subsequent years. The study revealed that some tree species, in particular Quercus sp., host a particular high diversity of saproxylic beetles, but tree species with a comparatively medium or low overall diversity were likewise important for red-listed saproxylic beetle species. Compared to native tree species, non-native tree species hosted a similar overall species diversity of saproxylic beetles but differed in community composition. In chapter IV, I finally analysed the interactions of host beetle diversity and the diversity of associated parasitoids by using experimentally manipulated communities of saproxylic beetles and parasitoid Hymenoptera as a model system. Classical approaches of species identification for saproxylic beetles were combined with DNA-barcoding for parasitoid Hymenoptera. The diversity of the host communities was inferred from their phylogenetic composition as well as differences in seven functional traits. Abundance, species richness, and Shannon-diversity of parasitoid Hymenoptera increased with increasing host abundance. However, the phylogenetic and functional dissimilarity of host communities showed no influence on the species communities of parasitoid Hymenoptera. The results clearly indicate an abundance-driven system in which the general availability, not necessarily the diversity of potential hosts, is decisive. In summary, the present thesis corroborates the general importance of deadwood heterogeneity for the diversity of saproxylic species by combining different experimental approaches. In order to increase their efficiency, conservation strategies for saproxylic species should generally promote deadwood from different tree species under different conditions of sun exposure on landscape-level in addition to the present enrichment of a certain deadwood amount. The most effective combinations of tree species should consider broadleaved and coniferous as well as hard- and softwood tree species. Furthermore, in addition to dominant tree species, special attention should be given to native, subdominant, silviculturally unimportant, and rare tree species.},
  language  = {en}
}
@phdthesis{İşbilir2022,
  author    = {İ{\c{s}}bilir, Ali},
  title     = {Localization and Trafficking of CXCR4 and CXCR7},
  doi       = {10.25972/OPUS-24937},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249378},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {G protein-coupled receptors (GPCRs) constitute the largest class of membrane proteins, and are the master components that translate extracellular stimulus into intracellular signaling, which in turn modulates key physiological and pathophysiological processes. Research within the last three decades suggests that many GPCRs can form complexes with each other via mechanisms that are yet unexplored. Despite a number of functional evidence in favor of GPCR dimers and oligomers, the existence of such complexes remains controversial, as different methods suggest diverse quaternary organizations for individual receptors. Among various methods, high resolution fluorescence microscopy and imagebased fluorescence spectroscopy are state-of-the-art tools to quantify membrane protein oligomerization with high precision. This thesis work describes the use of single molecule fluorescence microscopy and implementation of two confocal microscopy based fluorescence fluctuation spectroscopy based methods for characterizing the quaternary organization of two class A GPCRs that are important clinical targets: the C-X-C type chemokine receptor 4 (CXCR4) and 7 (CXCR7), or recently named as the atypical chemokine receptor 3 (ACKR3). The first part of the results describe that CXCR4 protomers are mainly organized as monomeric entities that can form transient dimers at very low expression levels allowing single molecule resolution. The second part describes the establishment and use of spatial and temporal brightness methods that are based on fluorescence fluctuation spectroscopy. Results from this part suggests that ACKR3 forms clusters and surface localized monomers, while CXCR4 forms increasing amount of dimers as a function of receptor density in cells. Moreover, CXCR4 dimerization can be modulated by its ligands as well as receptor conformations in distinct manners. Further results suggest that antagonists of CXCR4 display distinct binding modes, and the binding mode influences the oligomerization and the basal activity of the receptor: While the ligands that bind to a "minor" subpocket suppress both dimerization and constitutive activity, ligands that bind to a distinct, "major" subpocket only act as neutral antagonists on the receptor, and do not modulate neither the quaternary organization nor the basal signaling of CXCR4. Together, these results link CXCR4 dimerization to its density and to its activity, which may represent a new strategy to target CXCR4.},
  subject      = {G-Protein gekoppelter Rezeptor},
  language  = {en}
}
@phdthesis{Haider2022,
  author    = {Haider, Malik Salman},
  title     = {Structure Property Relationship and Therapeutic Potential of Poly(2-oxazoline)s and Poly(2-oxazines)s based Amphiphiles},
  doi       = {10.25972/OPUS-28903},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-289036},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In the past decade, poly(2-oxazoline)s (POx) and very recently poly(2-oxazine)s (POzi) based amphiphiles have shown great potential for medical applications. Therefore, the major aim of this thesis was to further explore the pharmaceutical and biomedical applications of POx/POzi based ABA triblock and AB diblock copolymers, respectively with the special emphasis on structure property relationship (SPR). ABA triblock copolymers (with shorter side chain length in the hydrophobic block) have shown high solubilizing capacity for hydrophobic drugs. The issue of poor aqueous solubility was initially addressed by developing a (micellar) formulation library of 21 highly diverse, hydrophobic drugs with POx/POzi based ABA triblock copolymers. Theoretically, the extent of compatibility between polymers and drug was determined by calculating solubility parameters (SPs). The SPs were thoroughly investigated to check their applicability in present systems. The selected formulations were further characterized by various physico-chemical techniques. For the biomedical applications, a novel thermoresposive diblock copolymer was synthesized which has shown promising properties to be used as hydrogel bioink or can potentially be used as fugitive support material. The most important aspect i.e. SPR, was studied with respect to hydrophilic block in either tri- or di-block copolymers. In triblock copolymer, the hydrophilic block played an important role for ultra high drug loading, while in case of diblock, it has improved the printability of the hydrogels. Apart from the basic research, the therapeutic applications of two formulations i.e. mitotane (commercially available as tablet dosage form for adrenocortical carcinoma) and BT-44 (lead compound for nerve regeneration) were studied in more detail.},
  language  = {en}
}
@phdthesis{Lechner2022,
  author    = {Lechner, Theresa},
  title     = {Proximal Methods for Nonconvex Composite Optimization Problems},
  doi       = {10.25972/OPUS-28907},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-289073},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Optimization problems with composite functions deal with the minimization of the sum of a smooth function and a convex nonsmooth function. In this thesis several numerical methods for solving such problems in finite-dimensional spaces are discussed, which are based on proximity operators. After some basic results from convex and nonsmooth analysis are summarized, a first-order method, the proximal gradient method, is presented and its convergence properties are discussed in detail. Known results from the literature are summarized and supplemented by additional ones. Subsequently, the main part of the thesis is the derivation of two methods which, in addition, make use of second-order information and are based on proximal Newton and proximal quasi-Newton methods, respectively. The difference between the two methods is that the first one uses a classical line search, while the second one uses a regularization parameter instead. Both techniques lead to the advantage that, in contrast to many similar methods, in the respective detailed convergence analysis global convergence to stationary points can be proved without any restricting precondition. Furthermore, comprehensive results show the local convergence properties as well as convergence rates of these algorithms, which are based on rather weak assumptions. Also a method for the solution of the arising proximal subproblems is investigated. In addition, the thesis contains an extensive collection of application examples and a detailed discussion of the related numerical results.},
  subject      = {Optimierung},
  language  = {en}
}
@phdthesis{Ryma2022,
  author    = {Ryma, Matthias},
  title     = {Exploiting the Thermoresponsive Properties of Poly(2-oxazoline)s for Biofabrication},
  doi       = {10.25972/OPUS-24746},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-247462},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In this thesis, non-modified POx, namely PnPrOx and PcycloPrOx, with an LCST in the physiological range between 20 and 37°C have been utilized as materials for three different biofabrication approaches. Their thermoresponsive behavior and processability were exploited to establish an easy-to-apply coating for cell sheet engineering, a novel method to create biomimetic scaffolds based on aligned fibrils via Melt Electrowriting (MEW) and the application of melt electrowritten sacrificial scaffolds for microchannel creation for hydrogels. Chapter 3 describes the establishment of a thermoresponsive coating for tissue culture plates. Here, PnPrOx was simply dissolved in water and dried in well plates and petri dishes in an oven. PnPrOx adsorbed to the surface, and the addition of warm media generated a cell culture compatible coating. It was shown that different cell types were able to attach and proliferate. After confluency, temperature reduction led to the detachment of cell sheets. Compared to standard procedures for surface coating, the thermoresponsive polymer is not bound covalently to the surface and therefore does not require specialized equipment and chemical knowledge. However, it should be noted that the detachment of the cell layer requires the dissolution of the PnPrOx-coating, leading to possible polymer contamination. Although it is only a small amount of polymer dissolved in the media, the detached cell sheets need to be washed by media exchange for further processing if required. ...},
  subject      = {Thermoresponsive Polymere},
  language  = {en}
}
@phdthesis{Warnecke2022,
  author    = {Warnecke, Sandra},
  title     = {Numerical schemes for multi-species BGK equations based on a variational procedure applied to multi-species BGK equations with velocity-dependent collision frequency and to quantum multi-species BGK equations},
  edition   = {1. Auflage},
  publisher = {W{\"u}rzburg University Press},
  address   = {W{\"u}rzburg},
  isbn      = {978-3-95826-192-1},
  doi       = {10.25972/WUP-978-3-95826-193-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282378},
  school      = {W{\"u}rzburg University Press},
  pages     = {xiii, 203},
  year      = {2022},
  abstract  = {We consider a multi-species gas mixture described by a kinetic model. More precisely, we are interested in models with BGK interaction operators. Several extensions to the standard BGK model are studied. Firstly, we allow the collision frequency to vary not only in time and space but also with the microscopic velocity. In the standard BGK model, the dependence on the microscopic velocity is neglected for reasons of simplicity. We allow for a more physical description by reintroducing this dependence. But even though the structure of the equations remains the same, the so-called target functions in the relaxation term become more sophisticated being defined by a variational procedure. Secondly, we include quantum effects (for constant collision frequencies). This approach influences again the resulting target functions in the relaxation term depending on the respective type of quantum particles. In this thesis, we present a numerical method for simulating such models. We use implicit-explicit time discretizations in order to take care of the stiff relaxation part due to possibly large collision frequencies. The key new ingredient is an implicit solver which minimizes a certain potential function. This procedure mimics the theoretical derivation in the models. We prove that theoretical properties of the model are preserved at the discrete level such as conservation of mass, total momentum and total energy, positivity of distribution functions and a proper entropy behavior. We provide an array of numerical tests illustrating the numerical scheme as well as its usefulness and effectiveness.},
  subject      = {Kinetische Gastheorie},
  language  = {en}
}
@phdthesis{Elsner2022,
  author    = {Elsner, Clara Dorothea},
  title     = {Ultrastructural analysis of biogenesis and release of endothelial extracellular vesicles},
  doi       = {10.25972/OPUS-28852},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288526},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Extracellular vesicle (EV)-mediated intercellular communication through exosomes, microvesicles (MVs) and apoptotic bodies has been shown to be implicated in various physiological as well as pathological processes such as the development and progression of atherosclerosis. While the cellular machinery controlling EV formation and composition has been studied extensively, little is known about the underlying morphological processes. This study focuses on a detailed ultrastructural analysis of the different steps of EV formation and release in Myocardial Endothelial (MyEnd) and Aortic Endothelial (AoEnd) cells cultured under serum starvation and inflammatory stimulation with TNF-α. Detailed morphological analyses were conducted applying and comparing different high- resolution light and electron microscopic methods. In this study, we could depict all steps of MV biogenesis named in literature. However, during the study of exosome biogenesis, we discovered a yet undescribed process: Instead of a direct fusion with the plasma membrane, multivesicular bodies were incorporated into a new distinct cellular compartment bound by fenestrated endothelium first. This may present a novel step in exosome biogenesis and warrants further study. Regarding the conditions of cell cultivation, we observed that the commonly used serum starvation causes MyEnd cells, but not AoEnd cells, to enter apoptosis after 48 hours. When preparing functional EV studies, we therefore recommend assessing the morphological condition of the serum-starved cells at different cultivation points first. When evaluating MV production, a statistical analysis showed that the more time AoEnd cells spent in cultivation under serum starvation, the higher the percentage of MV producing cells. However, additional TNF-α stimulation induced a significantly higher MV production than serum starvation alone. Lastly, our results show that TNF-α stimulation of AoEnd cells in vitro leads to the upregulation of CD44, an adhesion molecule critical in the early stages of atherosclerosis. CD44 was then depicted on the surface of generated MVs and exosomes. We conclude that under inflammatory conditions, EVs can mediate the transfer of CD44 from endothelial cells to target cells. This could be a novel mechanism by which MVs contribute to the development and progression of atherosclerotic disease and should be clarified by further studies.},
  subject      = {Vesikel},
  language  = {en}
}
@phdthesis{vonSchoenfeld2022,
  author    = {von Sch{\"o}nfeld, Cornelia},
  title     = {Universal prevention of nonsuicidal self-injury for children and adolescents - A systematic review -},
  doi       = {10.25972/OPUS-28702},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287020},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In a synopsis of the current state of research regarding NSSI, there are two key findings of this thesis: Firstly, there is a severe scarcity of studies and currently no evidence base for effective universal prevention of NSSI in youth. Secondly, not only the number but also quality of those few studies found was considered too low to draw wide-ranging conclusions and no meta-analysis could be conducted. This conclusion based - among other factors listed in chapter six - on the application of the EPHPP quality assessment tool (Evans, Lasen et al. 2015), which revealed distinct deficiencies and a weak overall study quality for all seven studies. Even if the high prevalence of NSSI among adolescents and the importance of this field of research is increasingly emphasized in contemporary literature (Muehlenkamp, Walsh et al. 2010, Wasserman, Carli et al. 2010, Brunner, Kaess et al. 2014, Plener, Schumacher et al. 2015), the shortage of concrete programs addressing the issue is manifest. The potential to tackle NSSI via prevention is underlined in view of the fact that many recent studies prove the high potential of primary prevention regarding NSSI incidences (Evans, Hawton et al. 2005, Fortune, Sinclair et al. 2008). From the studies included for this review, it can be concluded that most interventions show positive effects in raising awareness, knowledge, understanding of risk factors and help-seeking attitudes among school staff or students, particularly when starting with low knowledge at baseline (Robinson, Gook et al. 2008). Yet, most studies focus on training of gatekeepers and only two programmes address students directly and primarily measure actual NSSI behaviour. This finding highlights the importance of more investigation into concrete NSSI measurement targeting mainly the group of youth. There is a severe lack of literature on primary prevention with suitable contexts and target groups, while reviews on secondary targeted prevention deliver much more potential in the quantity of research (Kothgassner, Robinson et al. 2020, Kothgassner, Goreis et al. 2021). Until that changes, secondary prevention approaches of NSSI should be relied upon first. Looking into the future, several considerations may help advance universal approaches to NSSI. Regarding study planning, it is crucial for future research to pursue a thorough background research, examine the feasibility of interventions, and evaluate the appropriateness of study samples chosen. Moreover, research groups are expected to ensure a close observation of participants in cases of adverse events, in order to offer support, but also detect potential deficiencies in the study organisation. Additionally - in accordance with other research in this field (Plener, Brunner et al. 2010) - findings of this review highlight the necessity to expand fundamental research on functions of NSSI and its (neurobiological) mechanism of formation in order to enhance the knowledge of correlations and improve effective preventive approaches. As psychoeducational methods have shown risks of iatrogenic effects (e.g. in patients with eating disorders) (Stice, 2007 \#10063), it might be worthwhile to focus on improving emotion regulation in order to strengthen protective factors and improve adolescents' management of their everyday lives rather than on merely mitigating possible risk factors. Regarding intervention costs, it appears indispensable to include more cost calculations in the study planning of future research. In contrast to therapeutic interventions of NSSI, which are usually conducted in an in-patient setting and entail high measurable expenses as compared to preventive interventions, preventive approaches may in case of success result in a reduction of clinical presentation (O'Connell, Boat et al. 2009). A promising outlook is entailed by study protocol presenting a skills-based universal prevention program of NSSI "DUDE", a cluster randomized controlled trial scheduled for 16 German schools with a total of 3.200 adolescents (Buerger, Emser et al. 2022). The program is tailored to decrease the incidence of NSSI and avert potential and associated long-term consequences like suicidality among adolescents. It is aimed to provide easy access for adolescents due to its implementation during lesson time at school and is declared cost-effective. Furthermore, DUDE is a promising approach to effective NSSI prevention, as it is intended to improve mental health through the pathway of emotion regulation. It remains to await the implementation of the protocol, which is currently delayed due to the SARS-CoV-19 pandemic. In sum, initial research is promising and suggests that the approach to tackle NSSI via prevention is meaningful. Yet, high-quality studies on the development and evaluation of universal NSSI prevention in adolescents are urgently needed.},
  language  = {en}
}
@phdthesis{Gebert2022,
  author    = {Gebert, Friederike},
  title     = {Mammals and dung beetles along elevational and land use gradients on Mount Kilimanjaro: diversity, traits and ecosystem services},
  doi       = {10.25972/OPUS-19195},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191950},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Despite belonging to the best described patterns in ecology, the mechanisms driving biodiversity along broad-scale climatic gradients, like the latitudinal gradient in diversity, remain poorly understood. Because of their high biodiversity, restricted spatial ranges, the continuous change in abiotic factors with altitude and their worldwide occurrence, mountains constitute ideal study systems to elucidate the predictors of global biodiversity patterns. However, mountain ecosystems are increasingly threatened by human land use and climate change. Since the consequences of such alterations on mountainous biodiversity and related ecosystem services are hardly known, research along elevational gradients is also of utmost importance from a conservation point of view. In addition to classical biodiversity research focusing on taxonomy, the significance of studying functional traits and their prominence in biodiversity ecosystem functioning (BEF) relationships is increasingly acknowledged. In this dissertation, I explore the patterns and drivers of mammal and dung beetle diversity along elevational and land use gradients on Mt. Kilimanjaro, Tanzania. Furthermore, I investigate the predictors of dung decomposition by dung beetles under different extinction scenarios. Mammals are not only charismatic, they also fulfil important roles in ecosystems. They provide important ecosystem services such as seed dispersal and nutrient cycling by turning over high amounts of biomass. In chapter II, I show that mammal diversity and community biomass both exhibited a unimodal distribution with elevation on Mt.Kilimanjaro and were mainly impacted by primary productivity, a measure of the total food abundance, and the protection status of study plots. Due to their large size and endothermy, mammals, in contrast to most arthopods, are theoretically predicted to be limited by food availability. My results are in concordance with this prediction. The significantly higher diversity and biomass in the Kilimanjaro National Park and in other conservation areas underscore the important role of habitat protection is vital for the conservation of large mammal biodiversity on tropical mountains. Dung beetles are dependent on mammals since they rely upon mammalian dung as a food and nesting resource. Dung beetles are also important ecosystem service providers: they play an important role in nutrient cycling, bioturbation, secondary seed dispersal and parasite suppression. In chapter III, I show that dung beetle diversity declined with elevation while dung beetle abundance followed a hump-shaped pattern along the elevational gradient. In contrast to mammals, dung beetle diversity was primarily predicted by temperature. Despite my attempt to accurately quantifiy mammalian dung resources by calculating mammalian defecation rates, I did not find an influence of dung resource availability on dung beetle richness. Instead, higher temperature translated into higher dung beetle diversity. Apart from being important ecosystem service providers, dung beetles are also model organisms for BEF studies since they rely on a resource which can be quantified easily. In chapter IV, I explore dung decomposition by dung beetles along the elevational gradient by means of an exclosure experiment in the presence of the whole dung beetle community, in the absence of large dung beetles and without any dung beetles. I show that dung decomposition was the highest when the dung could be decomposed by the whole dung beetle community, while dung decomposition was significantly reduced in the sole presence of small dung beetles and the lowest in the absence of dung beetles. Furthermore, I demonstrate that the drivers of dung decomposition were depend on the intactness of the dung beetle community. While body size was the most important driver in the presence of the whole dung beetle community, species richness gained in importance when large dung beetles were excluded. In the most perturbed state of the system with no dung beetles present, temperature was the sole driver of dung decomposition. In conclusion, abiotic drivers become more important predictors of ecosystem services the more the study system is disturbed. In this dissertation, I exemplify that the drivers of diversity along broad-scale climatic gradients on Mt. Kilimanjaro depend on the thermoregulatory strategy of organisms. While mammal diversity was mainly impacted by food/energy resources, dung beetle diversity was mainly limited by temperature. I also demonstrate the importance of protected areas for the preservation of large mammal biodiversity. Furthermore, I show that large dung beetles were disproportionately important for dung decomposition as dung decomposition significantly decreased when large dung beetles were excluded. As regards land use, I did not detect an overall effect on dung beetle and mammal diversity nor on dung beetle-mediated dung decomposition. However, for the most specialised mammal trophic guilds and dung beetle functional groups, negative land use effects were already visible. Even though the current moderate levels of land use on Mt. Kilimanjaro can sustain high levels of biodiversity, the pressure of the human population on Mt. Kilimanjaro is increasing and further land use intensification poses a great threat to biodiversity. In synergy wih land use, climate change is jeopardizing current patterns and levels of biodiversity with the potential to displace communities, which may have unpredictable consequences for ecosystem service provisioning in the future.},
  subject      = {Kilimandscharo},
  language  = {en}
}
@phdthesis{Lewerentz2022,
  author    = {Lewerentz, Anne F.},
  title     = {Spatiotemporal dynamics of freshwater macrophytes in Bavarian lakes under environmental change},
  doi       = {10.25972/OPUS-28770},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287700},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Macrophytes are key components of freshwater ecosystems because they provide habitat, food, and improve the water quality. Macrophyte are vulnerable to environmental change as their physiological processes depend on changing environmental factors, which themselves vary within a geographical region and along lake depth. Their spatial distribution is not well understood and their importance is publicly little-known. In this thesis, I have investigated the spatiotemporal dynamics of freshwater macrophytes in Bavarian lakes to understand their diversity pattern along different scales and to predict and communicate potential consequences of global change on their richness. In the introduction (Chapter 1), I provide an overview of the current scientific knowledge of the species richness patterns of macrophytes in freshwater lakes, the influences of climate and land-use change on macrophyte growth, and different modelling approaches of macrophytes. The main part of the thesis starts with a study about submerged and emergent macrophyte species richness in natural and artificial lakes of Bavaria (Chapter 2). By analysing publicly available monitoring data, I have found a higher species richness of submerged macrophytes in natural lakes than in artificial lakes. Furthermore, I showed that the richness of submerged species is better explained by physio-chemical lake parameters than the richness of emergent species. In Chapter 3, I considered that submerged macrophytes grow along a depth gradient that provides a sharp environmental gradient on a short spatial scale. This study is the first comparative assessment of the depth diversity gradient (DDG) of macrophytes. I have found a hump-shaped pattern of different diversity components. Generalised additive mixed-effect models indicate that the shape of the DDG is influenced mainly by light quality, light quantity, layering depth, and lake area. I could not identify a general trend of the DDG within recent years, but single lakes show trends leading into different directions. In Chapter 4, I used a mechanistic eco-physiological model to explore changes in the distribution of macrophyte species richness under different scenarios of environmental conditions across lakes and with depths. I could replicate the hump-shaped pattern of potential species richness along depth. Rising temperature leads to increased species richness in all lake types, and depths. The effect of turbidity and nutrient change depends on depth and lake type. Traits that characterise "loser species" under increased turbidity and nutrients are a high light consumption and a high sensibility to disturbances. "Winner species" can be identified by a high biomass production. In Chapter 5, I discuss the image problem of macrophytes. Unawareness, ignorance, and the poor accessibility of macrophytes can lead to conflicts of use. I assumed that an increased engagement and education could counteract this. Because computer games can transfer knowledge interactively while creating an immersive experience, I present in the chapter an interactive single-player game for children. Finally, I discuss the findings of this thesis in the light of their implications for ecological theory, their implications for conservation, and future research ideas (Chapter 6). The findings help to understand the regional distribution and the drivers of macrophyte species richness. By applying eco-physiological models, multiple environmental shaping factors for species richness were tested and scenarios of climate and land-use change were explored.},
  subject      = {{\"O}kologie},
  language  = {en}
}
@phdthesis{Djaković2022,
  author    = {Djaković, Lara},
  title     = {The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes},
  doi       = {10.25972/OPUS-24670},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246709},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Herpes Simplex Virus type 1 (HSV-1) is an ubiquitous neurotropic human pathogen that infects a large majority of the world's population. It is the causative agent of the common cold sore but also responsible for life-threatening infections (e.g., encephalitis), particularly in immunocompromised individuals and neonates. Like other herpesviruses, HSV-1 takes over the cellular RNA machinery to facilitate productive infection while efficiently shutting down host gene expression by targeting multiple steps of RNA metabolism. The two viral proteins, vhs and ICP27, play a crucial role in this process. Delivered by the tegument of the incoming virus, the virion host shut-off (vhs) endonuclease rapidly starts cleaving both cellular and viral mRNAs. With the onset of viral gene expression, the HSV-1 immediate-early protein ICP27 promotes the expression of viral early and late genes through various mechanisms, including mRNA processing, export, and translation. Prior research by the D{\"o}lken lab demonstrated that lytic HSV-1 infection results in the disruption of transcription termination (DoTT) of most cellular genes by the viral ICP27 protein. This significantly contributes to HSV-1 induced host shut-off. DoTT results in transcription for tens of thousands of nucleotides beyond poly(A) sites and into downstream genes. Interestingly, this was found to be accompanied by a dramatic increase in chromatin accessibility downstream of the affected poly(A) sites. This is consistent with the formation of extensive downstream open chromatin regions (dOCR) and indicative of impaired histone repositioning in the wake of RNA polymerase II (Pol II) downstream of the affected poly(A) sites. In my PhD thesis, I demonstrate that dOCR formation is dependent on the viral ICP22 protein when poly(A) read-through transcription is triggered by the ectopic expression of ICP27 or salt stress. I show that dOCR formation occurs when a high level of transcriptional activity arises downstream of genes due to the HSV-1-induced DoTT. To investigate whether histone composition is affected downstream of genes, I established the ChIPmentation approach to study associated changes and the influence of DoTT and dOCR formation on major histone modification marks. In HSV-1 WT infection, dOCR formation was reflected in alterations of canonical H1 histone downstream of affected genes, which was absent in ICP22 infection. To elucidate the underlying molecular mechanism, two major histone chaperones SPT6 and FACT (SPT16 and SSRP1), which govern histone repositioning and may thus play a role in H1 homeostasis, were extensively studied. Both histone chaperones have been recently shown to be recruited to the viral genome by interactions with ICP22 protein. To investigate whether the depletion of SSRP1 or SPT6 would complement the loss of ICP22 to induce dOCR, T-HF cells with doxycycline-inducible knock-down of either of the two factors were generated. ATAC-seq analysis revealed that the interaction between the two histone chaperones and ICP22 is not involved in HSV-1-induced dOCR formation, suggesting the involvement of other proteins. In summary, this work sheds new light on a fundamental molecular mechanism of the cellular transcriptional machinery that is manipulated by the concerted actions of the two HSV-1 immediate-early proteins ICP22 and ICP27.},
  subject      = {HSV-1},
  language  = {en}
}
@phdthesis{Liesner2022,
  author    = {Liesner, Marvin Paul},
  title     = {I control it, but does it mean it is part of me? How the relationship between body movements and controlled object movements influences the sense of agency and the sense of ownership},
  doi       = {10.25972/OPUS-28703},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287030},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The "active self" approach suggests that any object we manipulate voluntarily and foreseeably becomes part of our "self" in the sense that we feel control over this object (sense of agency) and experience it as belonging to our own body (sense of ownership). While there is considerable evidence that we can indeed experience both a sense of agency and a sense of ownership over a broad variety of objects when we control these through our actions, the approach has also been criticized for exaggerating the flexibility of the human self. In this thesis, I investigate the influence that the relationship between the body movements controlling an object and the movements of the object itself has on the process of integrating an object into the self. I demonstrate that fully controlling an object is not sufficient for it to be integrated into the self since both explicit and implicit measures of the sense of agency and the sense of ownership indicate less or no integration when body movements are transformed into inverted object movements. Furthermore, I show that such inversions lead to the downregulation of sensory signals either from the body or from the controlled object in order to deal with the conflicting multisensory information when performing such actions. I argue that this downregulation is the underlying factor behind the diminished or eliminated integration of inverted body and object movements and I discuss further pathways for possible future studies building up on these findings.},
  subject      = {Experimentelle Psychologie},
  language  = {en}
}
@phdthesis{Oberndorfer2022,
  author    = {Oberndorfer, Florian},
  title     = {Photoluminescence and Raman spectroscopy of doped nanomaterials},
  doi       = {10.25972/OPUS-27854},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278540},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {This thesis includes measurements that were recorded by cooperation partners. The EPR spec- trosa mentioned in section 5.2 were recorded by Michael Auth from the Dyakonov Group (Ex- perimental Physics VI, Julius-Maximilians-Universit{\"a}t, W{\"u}rzburg). The TREFISH experiments and transient absorption in section 5.4 spectra were performed by Jašinskas et al. from the V. Gulbi- nas group (Center for Physical Sciences and Technology, Vilnius, Lithuania). This dissertation investigated the interactions of semiconducting single-walled carbon nanotubes (SWNTs) of (6,5) chirality with their environment. Shear-mixing provided high-quality SWNT sus- pensions, which was complemented by various film preparation techniques. These techniques were in turn used to prepare heterostructures with MoS2 and hBN, which were examined with a newly constructed photoluminescence microscope specifically for this purpose. Finally, the change of spectral properties of SWNTs upon doping was investigated in more detail, as well as the behaviour of charge carriers in the tubes themselves. To optimise the SWNT sample preparation techniques that supplied the other experiments, the sample quality of shear-mixed preparations was compared with that of sonicated samples. It was found that the quantum efficiency of sheared suspensions exceeds that of sonicated suspensions as soon as the sonication time exceeds 30 min. The higher PLQY is due to the lower defect concentration in shear-mixed samples. Via transient absorption, a mean lifetime of 17.3 ps and a mean distance between defects of 192.1 nm could be determined. Furthermore, it was found that the increased efficiency of horn sonication is probably not only due to higher shear forces acting on the SWNT bundles but also that the shortening of PFO-BPy strands plays a significant role. Sonication of very long polymer strands significantly increased their effectiveness in shear mixing. While previous approaches could only achieve very low concentrations of SWNTs in suspensions, pre-sonicated polymer yielded results which were comparable with much shorter PFO-BPy batches. Reference experiments also showed that different aggregation processes are relevant during production and further processing. Initial reprocessing of carbon nanotube raw material requires 7 h sonication time and over 24 h shear mixing before no increase in carbon nano concentration is detectable. However, only a few minutes of sonication or shear mixing are required when reprocessing the residue produced during the separation of the slurry. This discrepancy indicates that different aggregates are present, with markedly different aggregation properties. To study low-dimensional heterostructures, a PL microscope was set up with the ability to ob- serve single SWNTs as well as monolayers of other low-dimensional systems. Furthermore, sam- ples were prepared which bring single SWNTs into contact with 2D materials such as h-BN andMoS2 layers and the changes in the photoluminescence spectrum were documented. For h-BN, it was observed whether previous methods for depositing SWNTs could be transferred for photo- luminescence spectroscopy. SWNTs were successfully deposited on monolayers via a modified drip coating, with the limitation that SWNTs aggregate more at the edges of the monolayers. Upon contact of SWNTs with MoS2, significant changes in the emission properties of the mono- layers were observed. The fluorescence, which was mainly dominated by excitons, was shifted towards trion emission. Reference experiments excluded PFO-BPy and toluene as potential causes. Based on the change in the emission behaviour of MoS2, the most plausible explanation is a photoinduced charge transfer leading to delocalised charge carriers on MoS2. In contrast, on SWNTs, the introduction of additional charges would constitute a quenching centre, which would quench their PL emission, making them undetectable in the PL image. In the last chapter, the electronic properties of doped SWNTs and the behaviour of charge carri- ers inside the tubes should be investigated. First, the change in the conductivity of SWNT films with increasing doping levels was docu- mented. The resistance of the films drops drastically at minimum doping. After the initial in- troduction of charges, the resistance drops with increasing dopant concentration according to a double logarithmic curve. The initial drop could be due to a reduction of contact resistances within the SWNT network film, but this could not be further investigated within the scope of this PhD thesis. In cooperation with Andreas Sperlich and Michael Auth, the spin concentration of SWNTs at different doping levels was determined. The obtained concentrations were compared with the carrier concentrations determined from PL and absorption spectra. At low spin densities, good agreement with previous models was found. Furthermore, the presence of isolated spins strongly suggests a localised charge carrier distribution at temperatures around 10 K. When the charge density is increased, the spin density deviates significantly from the charge carrier con- centration. This discrepancy is attributed to the increasing delocalisation of charge carriers at high charge densities and the interactions of neighbouring spins. These results strongly indicate the existence of localised charge carriers in SWNTs at low temperatures. Next, the effect of doping on the Raman spectra of SWNT suspensions was investigated. In gen- eral, doping is expected to reduce the intensity of the Raman bands, i.e. a consequence of the reduced resonance gain due to bleaching of the S2 transition. However, similar to the resistivity measurements, the oscillator strength of the G+ band drops sharply in the first doping steps. It was also found that the G+ band decreases more than would be expected due to loss of reso- nance condition. Furthermore, the G- is bleached faster than the G+ band. All these anomalies suggest that resonance enhancement is not the only relevant effect. Another much faster deac- tivation path for the excitons may be introduced by doping. This would leave less time for the scattering process to occur and reduce the oscillator strength of the Raman bands. In cooperation with Vidmantas et al., the photoinduced charge carrier behaviour of SWNT/PCBM films was investigated. The required films were prepared by drop coating. The SWNT suspen- sions required for this were obtained from sheared SWNT preparations. Using transient absorp- tion and TREFISH, a number of charge transfer effects were identified and their dynamics in- vestigated: the recombination of neutral excitons (< 50 ps), the electron transfer from carbon nanotubes to PCBM molecules (< 1 ps), the decay of charge-transfer excitons (∼200 ps), the recombination of charge carriers between charge-transfer excitons (1 ns to 4 ns) and finally the propagation through the SWNT network (∼20 ns)},
  subject      = {Einwandige Kohlenstoff-Nanor{\"o}hre},
  language  = {en}
}
@phdthesis{Merz2022,
  author    = {Merz, Viktor},
  title     = {Funktionalisierung und Untersuchung von Nanodiamanten f{\"u}r biomedizinische und sensorische Anwendungen},
  doi       = {10.25972/OPUS-24588},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245888},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Nanodiamant (ND) ist ein vielseitiges und vielversprechendes Material f{\"u}r Bio-Anwendungen. Trotz vieler Bem{\"u}hungen bleibt die Agglomeration von Nanodiamant und die unspezifische Adsorption von Proteinen an der ND-Oberfl{\"a}che bei Kontakt mit Biofl{\"u}ssigkeiten ein großes Hindernis f{\"u}r biomedizinische Anwendungen. Eine Auswahl verzweigter und linearer Molek{\"u}le mit {\"u}berlegener F{\"a}higkeit zur kolloidalen Stabilisierung von Nanopartikeln in Salz- und Zellmedienumgebung, f{\"u}r bis zu 30 Tage, wurde an die ND-Oberfl{\"a}che angebracht. Das Baukastensystem mit Azid als Außengruppen bietet eine große Vielfalt an Bindungen mit vielen Molek{\"u}len, wie z. B. Medikamenten, Farbstoffen oder Targeting-Molek{\"u}len. Das Anh{\"a}ngen von z. B. Zwitterionen an die Kette sch{\"u}tzt die ND-Oberfl{\"a}che vor der Bildung einer Proteinkorona, wenn die Partikel mit proteinhaltigen Biofl{\"u}ssigkeiten in Kontakt kommen. Die Ergebnisse der thermogravimetrischen Analyse der Beladung der ND-Oberfl{\"a}che zeigen eine signifikante Verhinderung der Proteinadsorption von bis zu 98 \% im Vergleich zu NDs ohne zwitterionische Kopfgruppen und eine lange kolloidale Stabilit{\"a}t, wenn Tetraethylenglykol (TEG) an die Oberfl{\"a}che gebunden wird. Die Vielseitigkeit des modularen Systems, um nicht nur zwitterionische Ketten, sondern auch klickbare funktionelle Molek{\"u}le an fluoreszierende Nanodiamanten (fNDs) zu binden, zeigt das Potenzial des Systems am Nanodiamanten. Unter Verwendung von Defektstrukturen, wie Stickstoff-Vakanz-Zentren (NV), k{\"o}nnen Diamantpartikel aufgrund ihres weitgehend ungiftigen Verhaltens als fluoreszierende Nanodiamanten (fNDs) f{\"u}r photostabile Markierung, Bioimaging und nanoskalige Sensorik in lebenden Zellen und Organismen verwendet werden. Um die fND-Oberfl{\"a}che zu funktionalisieren, wurde eine neuartige Mahltechnik mit Diazoniumsalzen etabliert, um ein Pfropfen auf wenig reaktive HPHT-fNDs durchzuf{\"u}hren, was zu einer hohen Oberfl{\"a}chenbeladung und einem hohen negativen Zetapotenzial f{\"u}hrt. Die Kombination der Vorteile von TEG und zwitterionhaltigen Gruppen mit der F{\"a}higkeit zum Targeting von Antik{\"o}rpern auf fND best{\"a}tigt zum ersten Mal die verbesserte kolloidale Stabilit{\"a}t in Experimenten mit lebenden Zellen. Dar{\"u}ber hinaus deuten die Ergebnisse auf eine verbesserte Corona-Abstoßung im Vergleich zu fND ohne zwitterionhaltige Kopfgruppen hin. Infolgedessen wurden die Zirkulationszeiten von 4 (fND ohne Zwitterionenkette, aber mit Antik{\"o}rper) auf 17 (mit Antik{\"o}rper und Zwitterionenketten) Stunden vergr{\"o}ßert. In nicht-biomedizinischen Anwendungen kann das modulare System als Sonde f{\"u}r Schwermetalle durch die Anbindung von Farbstoffen verwendet werden. Die Detektion von Metallen in verschiedenen Umgebungen mit hoher Selektivit{\"a}t und Spezifit{\"a}t ist eine der Voraussetzungen f{\"u}r den Kampf gegen die Umweltverschmutzung mit diesen Elementen. Pyrene sind gut geeignet und weit bekannt f{\"u}r die Fluoreszenzsensorik in verschiedenen Medien. Das angewandte Sensorprinzip beruht typischerweise auf der Bildung von intra- und intermolekularen Excimeren, was jedoch den Empfindlichkeitsbereich aufgrund der Maskierung von z.B. Quenching-Effekten durch die Excimer-Emission einschr{\"a}nkt. Diese Studie zeigt einen hochselektiven, strukturstabilen chemischen Sensor, der auf der monomeren Fluoreszenz von Pyrenanteilen mit Triazolgruppen basiert. Dieser Sensor kann Cu2+, Pb2+ und Hg2+ in organischen L{\"o}sungsmitteln {\"u}ber einen weiten Konzentrationsbereich quantitativ nachweisen, auch in Gegenwart von ubiquit{\"a}ren Ionen wie Na+, K+, Ca2+ und Mg2+. Die stark emittierende Fluoreszenz des Sensors mit einer langen Lebensdauer von 165 ns wird durch eine 1:1-Komplexbildung bei Zugabe von Metallionen in Acetonitril gel{\"o}scht. Bei Zugabe eines zehnfachen {\"U}berschusses des Metallions zum Sensor bilden sich Agglomerate mit einem Durchmesser von etwa 3 nm. Aufgrund der komplexen Wechselwirkungen im System werden konventionelle lineare Korrelationen nicht f{\"u}r alle Konzentrationen beobachtet. Daher wird ein kritischer Vergleich zwischen der konventionellen Job-Plot-Interpretation, der Methode von Benesi-Hildebrand und einem nicht-linearen Fit vorgestellt. Das vorgestellte System erm{\"o}glicht die spezifische und robuste Erfassung von medizinisch und {\"o}kologisch relevanten Ionen im gesundheitsrelevanten nM-Bereich und k{\"o}nnte z. B. zur {\"U}berwachung der entsprechenden Ionen in Abfallstr{\"o}men eingesetzt werden. Doch h{\"a}ufig landen diese Abfallstr{\"o}me in empfindlichen Aquakulturen, wo eine solche Sensortechnik nur funktioniert, wenn die Sonde wasserl{\"o}slich ist, um die Ausbreitung und Bildung von Umweltsch{\"a}den durch Schwermetalle zu {\"u}berwachen. Viele Chemosensoren arbeiten nur in bestimmten L{\"o}sungsmitteln und unter hochreinen Bedingungen quantitativ. In dieser Arbeit wird eine Methode zur Stabilisierung von wasserunl{\"o}slichen Chemosensoren auf Nanodiamanten in salzhaltigem Wasser unter Beibehaltung der Sensoreffektivit{\"a}t und -spezifit{\"a}t sowie der kolloidalen Stabilit{\"a}t vorgestellt. Zus{\"a}tzlich wird die Sensorf{\"a}higkeit in organischen L{\"o}sungsmitteln beibehalten. Diese Studie gibt Einblick in die Absorptionsf{\"a}higkeit von Pyren-Derivaten an der Nanodiamant-Oberfl{\"a}che und einen Weg, diese reversibel zu desorbieren. Außerdem beweist das System, dass in Anwesenheit von 95 \% Sauerstoffatmosph{\"a}re bei der Fluoreszenzmessung die Ergebnisse nicht von denen in Argonatmosph{\"a}re abweichen. Dar{\"u}ber hinaus st{\"o}rt das Vorhandensein g{\"a}ngiger Ionen im Wasser die kolloidale Stabilit{\"a}t der NDs nicht und hat auch keinen Einfluss auf die Sensorfunktionalit{\"a}t und ist somit ein vielversprechender Kandidat f{\"u}r Messungen ohne aufw{\"a}ndige Pr{\"a}parationsschritte.},
  language  = {en}
}
@phdthesis{Awadallah2022,
  author    = {Awadallah, Abdelhaleem Aly Ahmed},
  title     = {The Crew of the Sun Bark in the Amduat},
  doi       = {10.25972/OPUS-28711},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287115},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The Amduat is one of the most important Netherworld Books which was recorded in various kinds of Ancient Egyptian sources since the beginning of the 18th dynasty, especially the walls of the royal tombs. The main theme of the Amduat is the journey of the sun god through the underworld where the solar bark and its crew is the central scene of the journey. The study focuses on finding the reasons of choosing the crew's members who manage the sun bark's journey in the Amduat. It also aims at illustrating the functions and responsibilities of each crew member. Following a historical approach, the study analyzes the Pyramid Texts and Coffin Texts as the most important documents before the New Kingdom, and proceeding to the inscriptions and writings of the monuments which contain portrayals and inscriptions of the Amduat in the New Kingdom. Furthermore, it sheds some light on the solar cycle's main features and primary aspects, and tries to scrutinize the date, meaning, and symbolisms of the Amduat and its indications in the earlier sources.},
  language  = {en}
}
@phdthesis{Graf2022,
  author    = {Graf, Dominic},
  title     = {Surface and active site modification of proteins with organometallic markers and inhibitors},
  doi       = {10.25972/OPUS-28742},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287424},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {After implementing a reliable mass spectrometry based kinetic study the indole conjugation with different organometallic indoles led to questions about the electronical and sterical influences on reactivity. The substitution pattern of the ferrocene functionalized indoles at the six-membered ring determines the electron density on the C3 atom, which reacts with the formed Schiff base. Since the experimental results showed the exact opposite trend, covalent docking studies were performed elucidating the importance of surface interactions. These studies were in harmony with the experimental results and determined lysine 33 as most preferable conjugation site as well as substitution in 6-position as most favourable pattern. The amine motif in compounds 6, 7 and 8 proofed to be easily fragmented by the ESI method used. The amide linker in 10 remains intact but shows a lower conversion. Those two inherent characteristics are however preferable for well-defined and site-specific bioconjugation. The synthesis and evaluation of piano stool complex derivatives with manganese and rhenium metal centre 15, 16, 18 and 22 gave additional guidance by the interpretation of applicable structural motifs. The electron-withdrawing carbonyl groups lead to the hindrance of fulvene formation and thus to no fragmentation as seen with the ferrocene group. The total conversion is low compared to 8, only 22 shows a good enough conversion to mainly monoconjugate of 45\% and a possible radio-labelling application as 99mTc analogue. As consequence manganese complexes with a stable facial tricarbonyl unit and a tridentate chelator with 4-, 5- and 6-substituted aminomethylindole conjugated through an amide bond were synthesized and consecutively evaluated. The resulting organometallic indole derivatives 29, 30 and 31 all showed a total conversion around 40\% similar to 16, but at the same time a rate constant in the range of 10-4 s-1 like the organic indole. Besides the similar conversion, the rate constants followed the trend of the 6-substituted derivative as fastest and then 5- and 4- substituted derivative with decreasing reactivity. For underlining the usage as technetium label for the best out of the series 31, a rhenium analogue was prepared. The resulting compound 32 was especially interesting, because the conversion was even higher than the 70\% of 8 with a total of 88\%. Additionally, the rate constant was a tenfold higher as well. This rendered compound 32 as best possible 99mTc analogue for further application as radio-label. After the success of 32 and realizing the sterical benefits resulting from the flexible tridentate ligand-system, substitution at the five-membered ring was explored. The complexes 33, 34 and 35 are based on indole-2-carboxylic acid and with the difference of the length of the alkyl spacer between amide and complex to probe for the influence and sterical hindrance, but all three derivatives showed no conjugation which excludes functionalization in 2-position. As the C3 is used for the actual bioconjugation, the last possible derivatization was realized on the indole-N1 by using 1-(3-bromopropyl)indole as building block during the synthesis of the ligand-system. The corresponding manganese 36 and rhenium 37 complexes both showed similar properties of a moderate conversion like 22 and a rate constant in the range of 10-5 s-1. In conclusion the rhenium complex 32 with the 6-substitution pattern at the tridentate indole-bearing ligand remains the most promising structure. The here developed liquid chromatography coupled mass spectrometry-based assay for the determination of inhibitory activity of drug candidates against the 3CLpro of the sever acute respiratory syndrome coronavirus type 2 was successfully implemented and especially designed to give, due to the available absorption spectra and corresponding mass traces, further insight in the otherwise through fluorescence resonance energy transfer-based assays neglected influences on the inhibition results. Starting with a literature-known quinolone containing covalent inhibitor 42 an N1-methylated derivative 43 and their analogues 44 and 45 in which the benzoic acid was exchanged for ferrocene carboxylic acid were synthesized. The inhibition of 3CLpro was evaluated by the concentration of initial 15mer peptide left after incubation and for that purpose the for 280 nm defined molar attenuation coefficient of (26.41±0.59) L*mol-1*cm-1 determined and used. The results showed a reaction of DL dithiothreitol with the less stable benzoic acid esters leading to a moderate inhibitory effect. The methylation in N1-position showed an increase in stability. The methylated and with ferrocene carboxylic acid functionalized derivative showed a complete inhibition during the timeframe of the assay. In search of a fluorescent and therefore traceable inhibitor, 4 hydroxycoumarin was used to synthesize the analogue with benzoic acid 49 and ferrocene carboxylic acid 50. Both derivatives were less stable than their analogues but exhibited the same trend of a more stable ferrocene-derived compound, which exerted a higher inhibition as well. After preparing and testing the model thioester 53 and showing an inactivation of the established inhibitor ebselen, it was concluded that the reaction with DL dithiothreitol reduces the concentration of active intact inhibitor and therefore decreases the inhibition rate during the assay. The next step was proofing the reducing agent as non-essential for the fast assay conducted in a timeframe of 5 min to circumvent the negative influence of DL dithiothreitol. By excluding every inhibition-altering part, the resulting method is the perfect tool for precise statements in relation of inhibitory activity. Then the inhibition assay was repeated for ebselen and the best out of the here introduced organometallic inhibitors 45. Both give equivalent results of a complete inhibition during the measurement. The implemented liquid chromatography coupled mass spectrometry-based assay has many advantages over the fluorescence resonance energy transfer-based assays in which all the information and insight accumulated by the evaluation of uv/vis traces and mass spectra are not available leading to wrong or deviating results regarding the inhibitory capacity of inhibitor candidates.},
  subject      = {Inhibition},
  language  = {en}
}
@phdthesis{Fricke2022,
  author    = {Fricke, Ute},
  title     = {Herbivory, predation and pest control in the context of climate and land use},
  doi       = {10.25972/OPUS-28732},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287328},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Chapter 1 - General introduction Anthropogenic land-use and climate change are the major drivers of the global biodiversity loss. Yet, biodiversity is essential for human well-being, as we depend on the availability of potable water, sufficient food and further benefits obtained from nature. Each species makes a somewhat unique contribution to these ecosystem services. Furthermore, species tolerate environmental stressors, such as climate change, differently. Thus, biodiversity is both the "engine" and the "insurance" for human well-being in a changing climate. Here, I investigate the effects of temperature and land use on herbivory (Chapter 2), predation (Chapter 3) and pest control (Chapter 4), and at the same time identify features of habitats (e.g. plant richness, proximity to different habitat types) and landscapes (e.g. landscape diversity, proportion of oilseed rape area) as potential management targets in an adaptation strategy to climate change. Finally, I discuss the similarities and differences between factors influencing herbivory, predation and pest control, while placing the observations in the context of climate change as a multifaceted phenomenon, and highlighting starting points for sustainable insect pest management (Chapter 5). Chapter 2 - Plant richness, land use and temperature differently shape invertebrate leaf-chewing herbivory on major plant functional groups Invertebrate herbivores are temperature-sensitive. Rising temperatures increase their metabolic rates and thus their demand for carbon-rich relative to protein-rich resources, which can lead to changes in the diets of generalist herbivores. Here, we quantified leaf-area loss to chewing invertebrates among three plant functional groups (legumes, non-leguminous forbs and grasses), which largely differ in C:N (carbon:nitrogen) ratio. This reseach was conducted along spatial temperature and land-use gradients in open herbaceous vegetation adjacent to different habitat types (forest, grassland, arable field, settlement). Herbivory largely differed among plant functional groups and was higher on legumes than forbs and grasses, except in open areas in forests. There, herbivory was similar among plant functional groups and on legumes lower than in grasslands. Also the presence of many plant families lowered herbivory on legumes. This suggests that open areas in forests and diverse vegetation provide certain protection against leaf damage to some plant families (e.g. legumes). This could be used as part of a conservation strategy for protected species. Overall, the effects of the dominant habitat type in the vicinity and diverse vegetation outweighed those of temperature and large-scale land use (e.g. grassland proportion, landscape diversity) on herbivory of legumes, forbs and grasses at the present time. Chapter 3 - Landscape diversity and local temperature, but not climate, affect arthropod predation among habitat types Herbivorous insects underlie top-down regulation by arthropod predators. Thereby, predation rates depend on predator community composition and behaviour, which is shaped by temperature, plant richness and land use. How the interaction of these factors affects the regulatory performance of predators was unknown. Therefore, we assessed arthropod predation rates on artificial caterpillars along temperature, and land-use gradients. On plots with low local mean temperature (≤ 7°C) often not a single caterpillar was attacked, which may be due to the temperature-dependent inactivity of arthropods. However, multi-annual mean temperature, plant richness and the dominant habitat type in the vicinity did not substantially affect arthropod predation rates. Highest arthropod predation rates were observed in diverse landscapes (2-km scale) independently of the locally dominanting habitat type. As landscape diversity, but not multi-annual mean temperature, affected arthropod predation rates, the diversification of landscapes may also support top-down regulation of herbivores independent of moderate increases of multi-annual mean temperature in the near future. Chapter 4 - Pest control and yield of winter oilseed rape depend on spatiotemporal crop-cover dynamics and flowering onset: implications for global warming Winter oilseed rape is an important oilseed crop in Europe, yet its seed yield is diminished through pests such as the pollen beetle and stem weevils. Damage from pollen beetles depends on pest abundances, but also on the timing of infestation relative to crop development as the bud stage is particularly vulnerable. The development of both oilseed rape and pollen beetles is temperature-dependent, while temperature effects on pest abundances are yet unknown, which brings opportunities and dangers to oilseed rape cropping under increased temperatures. We obtained measures of winter oilseed rape (flowering time, seed yield) and two of its major pests (pollen beetle, stem weevils) for the first time along both land-use and temperature gradients. Infestation with stem weevils was not influenced by any temperature or land-use aspect considered, and natural pest regulation of pollen beetles in terms of parasitism rates of pollen beetle larvae was low (< 30\%), except on three out of 29 plots. Nonetheless, we could identify conditions favouring low pollen beetle abundances per plant and high seed yields. Low pollen beetle densities were favoured by a constant oilseed rape area relative to the preceding year (5-km scale), whereas a strong reduction in area (> 40\%) caused high pest densities (concentration effect). This occurred more frequently in warmer regions, due to drought around sowing, which contributed to increased pollen beetle numbers in those regions. Yet, in warmer regions, oilseed rape flowered early, which possibly led to partial escape from pollen beetle infestation in the most vulnerable bud stage. This is also suggested by higher seed yields of early flowering oilseed rape fields, but not per se at higher temperatures. Thus, early flowering (e.g. cultivar selection) and the interannual coordination of oilseed rape area offer opportunities for environmental-friendly pollen beetle management. Chapter 5 - General discussion Anthropogenic land-use and climate change are major threats to biodiversity, and consequently to ecosystem functions, although I could show that ecosystem functions such as herbivory and predation barely responded to temperature along a spatial gradient at present time. Yet, it is important to keep several points in mind: (i) The high rate of climate warming likely reduces the time that species will have to adapt to temperature in the future; (ii) Beyond mean temperatures, many aspects of climate will change; (iii) The compensation of biodiversity loss through functional redundancy in arthropod communities may be depleted at some point; (iv) Measures of ecosystem functions are limited by methodological filters, so that changes may be captured incompletely. Although much uncertainty of the effects of climate and land-use change on ecosystem functions remains, actions to halt biodiversity loss and to interfere with natural processes in an environmentally friendly way, e.g. reduction of herbivory on crops, are urgently needed. With this thesis, I contribute options to the environment-friendly regulation of herbivory, which are at least to some extent climate resilient, and at the same time make a contribution to halt biodiversity loss. Yet, more research and a transformation process is needed to make human action more sustainable. In terms of crop protection, this means that the most common method of treating pests with fast-acting pesticides is not necessarily the most sustainable. To realize sustainable strategies, collective efforts will be needed targeted at crop damage prevention through reducing pest populations and densities in the medium to long term. The sooner we transform human action from environmentally damaging to biodiversity promoting, the higher is our insurance asset that secures human well-being under a changing climate.},
  subject      = {{\"O}kologie},
  language  = {en}
}
@phdthesis{Nagl2022,
  author    = {Nagl, Patrick Alexander},
  title     = {Chemistry meets Cancer Immunotherapy: Synthesis and Characterization of Hapten-like Compounds for Selective Immunotherapy},
  doi       = {10.25972/OPUS-21138},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211385},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Chimeric antigen receptors (CARs) are able to specifically direct T cells to tumor antigens and therapy with anti-CD19 CARs has already cured cancer patients with B-cell lymphomas who have undergone long-term therapy non-successful. Despite this impressive result, the therapy is currently only approved as a last treatment option for blood cancers due to its life-threatening deficiencies. For patient safety and to enable additional application such as the treatment of solid tumors, CAR-T cells must be controllable, e. g. by chemically programmable CARs (cpCARs) regulated by hapten-like compounds. This thesis reports the synthesis and characterization of such hapten-like compounds. In the first step, seven different warheads with two different spacers were bound to biotin in order to find a suitable warhead for programming the cpCAR. In a second step, synthetic routes for the three pharmacophores folate, c(RGD), and an RGD peptidomimetic were developed. The routes allow the modification of the pharmacophores with one of the warheads from the first step. CuAAC was chosen as a bioorthogonal approach to link pharmacophores and warheads. In total, three different pharmacophores were modified with the 1,3-diketone motif of compound 21 leading to 112, 113 and 128. Activation of the T-cell signaling cascade was tested after binding of these hapten-like compounds to the cpCAR in the presence of suitable target structures. For 112, only a slight, non-significant, activation of the T-cell signaling cascade was observed, whereas for 113 and 128, a significant activation of the T-cell signaling cascade was observed. The poor solubility of the folate compounds led to alternative strategies. Folic acid was exchanged by pteroic acid and the bifunctional, linear compounds were enlarged to trifunctional dendrimers. Besides the reported regioisomer in 112, a second one, which was not reported to date, occurred by the cyclization of the linear RGD pentapeptide leading to 113. After the reported synthesis of an RGD peptidomimetic analogous to 128 could not be reproduced, a new synthetic route was developed. It also consists of 17 steps, but reduces the number of linear steps from 13 to 10. Moreover, the developed route contains an asymmetric hydrogenation step and is, compared to the published one, more flexible by the use of the copper-catalyzed azide-alkyne cycloaddition (CuAAC). In addition, an unknown reaction was observed. Instead of the formation of a Schiff base in the reductive amination of 129, an insertion of propargylamine occurred forming 131. The reaction is almost quantitative and in high purity. After requiring no purification, it could be predestined for industrial purposes, such as the synthesis of N-functionalized 1,2-dihydroquinolines or as a building block with various orthogonal functional groups. Besides the sulfonamide 16, the diketone (21, 27, 31) and lactam compounds (39 - 41), experiments on adapter molecules with further warheads were performed. In the synthesis of a proadapter approach, in which the warhead is formed only after the retro-aldol reaction catalyzed by the mAb, 6 of 10 steps were successfully performed. A newly developed synthesis to keto-sulfonyl and keto-sulfoxide compounds could not be completed but was performed on a small scale to the point of keto-sulfonyl and keto-sulfoxide. Furthermore, a universal synthesis route was designed to allow the introduction of the warhead at the end of the synthesis by acylation. Thus, after 5 shared steps, 3 of them in quantitative yield, different warheads may be introduced. Moreover, this also facilitates the purification and the analysis of the compounds by the absence of tautomerism or labile groups. However, the acylation experiments were not successful with either the acid cyanide or the Weinreb amide. In summary, this thesis has proven that the 1,3-diketone motif is a suitable warhead for programming the cpCAR, which was developed by Hudecek et al. (unpublished data). The hapten-like compounds 112, 113 and 128 simultaneously bind to integrin \${\alpha}_v{\beta}_3\$ and the cpCAR activating the T-cell signaling cascade. The modular synthesis strategy and the use of the bioorthogonal CuAAC allow straightforward access to these valuable immunotherapeutics but revealed the need for an additional purification step to remove copper ions.},
  subject      = {Organische Synthese},
  language  = {en}
}
@phdthesis{Bergmann2022,
  author    = {Bergmann, Tim Jonas},
  title     = {Pathways in uremic cardiomyopathy - the intracellular orchestrator PGC-1α in cell culture and in a mouse model of uremia},
  doi       = {10.25972/OPUS-28706},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287061},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {For the past 20 years, chronic kidney disease (CKD) has remained one of the major causes of death worldwide. Cardiovascular events account for approximately 50\% of deaths in CKD patients, underscoring the clinical relevance of the observed cardiac changes. These changes define uremic cardiomyopathy (UCM) and include left-ventricular hypertrophy (LVH), LV dilatation, and LV systolic and diastolic dysfunction. LVH is seen as the primary manifestation of UCM and is caused by a multitude of different systems including in-creased pre- and afterload and the renin-angiotensin system (RAS). More recent studies found that myocardial dysfunction is apparent before changes in the ventricular geome-try, like hypertrophy, occur to the uremic heart. This leads to the conclusion that LVH is not the cause of cardiac dysfunction, but one of the alterations caused by factors related to the uremic state itself. Among these factors that are independent of pressure and vol-ume overload, are cardiotonic steroids as well as the parathyroid hormone and the endo-thelin (ET-1) system. But we suggest a different substance to play an important role in UCM: Urea. Patients in end-stage renal disease (ESRD) display increased oxidative stress and urea has been found to increase levels of oxidative stress, at least in endothelial cells. Therefore, we investigated the effect that elevated urea levels, as seen in patients undergoing dialysis, have on cardiomyocytes. As the oxidative stress in a cell is regulated by mitochondrial processes, we suspected the mitochondrial orchestrator PGC-1α to play an important role. The uremic heart is in a state of elevated oxidative stress. This has been presented by multiple authors before. By conducting immunofluorescent staining for reactive oxygen species (ROS), we tried to replicate their findings and illustrate elevated levels of ROS. As the fluorescence analysis did not bear significant results, we approached oxidative stress from a different angle: Via mass spectrometry, we looked at the amino acids methionine, cysteine and betaine which are highly involved in sustaining the oxidative balance in the cell. Our findings in the media of urea-treated HL-1 cells lead us to the conclusion, that these cardiomyocytes were in a state of low antioxidative resources. Next, to find the intracellular mechanisms that connect uremia to oxidative stress and compromised energetics, we investigated possible downstream effectors of uremia. The urea-treated cardiomyocytes exhibited significant alterations regarding upstream effec-tors of PGC-1α: The protein kinases Akt and Erk were expressed and phosphorylated dif-ferently in a western blot analysis of uremic h9c2 cells and in mice with induced kidney failure. To combine these findings regarding the protein kinases Akt and Erk and oxidative stress, the Erk/p38 pathways seems conclusive (figure 20). This pathway links uremia and oxidative stress to intracellular effectors that have been found to influence the develop-ment of uremic cardiomyopathy. Another life-threatening alteration in uremic cardiomyopathy is a corrupted cardiac func-tion. The myocardium of uremic patients has shown to be more susceptible to ischemic damage and most patients receiving dialysis experience repeated episodes of intradialytic impairments in cardiac function. The urea-treated cardiomyocytes had a significantly higher oxygen consumption rate due to an inefficiently increased metabolism, most likely caused by an increased level of uncoupling. Taken together, the results of this study indicate that urea by itself plays a role in the de-velopment of uremic cardiomyopathy. So-called high-physiologic levels of urea have led to a mitochondrial inefficiency and an increase of oxidative stress in cardiomyocytes. The protein kinases Akt and Erk may work as effectors of urea to induce these changes via the Erk/p38 pathway. It seems very likely that the mitochondrial changes are mediated by the mitochondrial orchestrator PGC-1α. These observations might lead to further studies in-vestigating urea levels in dialysis patients. In the future, these might lead to a change of practice regarding tolerated urea levels in dialysis and help reduce the cardiac mortality of patients with chronic kidney disease.},
  subject      = {Ur{\"a}mie},
  language  = {en}
}
@phdthesis{Mainz2022,
  author    = {Mainz, Laura},
  title     = {Cellular metabolism as target for cancer therapy},
  doi       = {10.25972/OPUS-21148},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211480},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Due to a usually late diagnosis, drug resistance and early metastases, pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of global cancer deaths. Thus, there is an urgent need to develop new therapeutic concepts. Two different approaches have in recent years become the focus of intense research: (1) targeting cancer-associated metabolic rearrangements, and (2) targeting genetic vulnerabilities with combination therapy. Both concepts potentially have advantages such as increased efficacy, which decreases the likelihood of therapy-resistance, and reduced side effects, that are often associated with high concentrations of chemotherapeutic drugs. Autophagy is an evolutionary conserved signalling pathway that regulates cellular homeostasis. Regarding cancer, autophagy can either promote or suppress tumor growth. However, mouse models that allow genetic regulation of autophagy in established tumor tissue are not yet established. Therefore, we analysed new inducible shRNA mouse models targeting Atg5 or Atg7 with regard to functionality and toxicity. Both, shRNA Atg5- and shRNA Atg7-mediated knockdown anteceded functional autophagy impairment, and revealed unexpected profound phenotypic differences. Knockdown of Atg5 neither impaired the animal nor caused any grossly or microscopically detectable organ damage, whereas knockdown of Atg7 caused pancreatic destruction and eventually death. It is currently unclear whether mice died as a result of exocrine or endocrine collapse or due to a combination of both. The presented mouse models are highly potent RNAi mice that allow widespread and regulable inhibition of autophagy upon administration of doxycycline and provide a valuable and versatile toolbox for future autophagy and cancer research. In PDAC, argininosuccinate synthase 1 (ASS1) deficiency has been associated with higher recurrence rates, shorter disease-free survival, and shorter overall survival. During cancer development, rate-limiting enzymes of de novo arginine synthesis, like ASS1 or OTC, are downregulated via epigenetic silencing of their respective promotor. Known as 'arginine auxotrophy', loss of these essential enzymes results in dependence on extracellular arginine. Based on this assumption, sensitivity of various cell lines to arginine deprivation was reported. However, the underlying mechanism is still unclear and the anti-tumor effects of the monotherapy are not sufficient to completely abrogate cancer cells. Therefore, the effects of arginine deprivation via rhArgI-PEG5000 were investigated in murine and human PDAC cells. In this study, we highlighted that arginine deprivation induced profound alterations such as autophagosome accumulation, induction of senescence and the ISR in pancreatic cancer cells. These alterations are potential genetic vulnerabilities that can be targeted by additional means to induce tumor cell death.},
  language  = {en}
}
@phdthesis{Liaqat2022,
  author    = {Liaqat, Anam},
  title     = {Artificial Evolution of Nucleic Acid Catalysts and their Use for Studying RNA},
  doi       = {10.25972/OPUS-28311},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283111},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {RNA molecules play diverse roles in biological systems. Post-transcriptional RNA modifications and dynamic structures enhance the functional diversity of RNA. A prerequisite for studying their biological significance is the availability of reliable methods for the detection of RNA modifications and structures. Several promising approaches have been developed in the last few decades; however, efficient, and versatile tools are still required to study the dynamic features of RNA. This thesis focuses on the development of nucleic acid catalysts as a tool to address the current needs in studying RNA. The major part of this thesis aimed at the development of deoxyribozymes as a tool for the detection of RNA modifications. Using in vitro selection from a random DNA library, we found deoxyribozymes that are sensitive to N 6 -isopentenyladenosine (i6A), a native tRNA modification and structural analogue of m6A. The in vitro evolution identified three classes of DNA enzymes: AA, AB08, and AC17 DNAzymes that showed distinct response to i6A modification and showed strong discrimination between structural analogues, i.e., m6A and i6A. In the continuation of the project, we attempted to develop RNA-cleaving deoxyribozymes that differentially respond to monomethylated cytidine isomers, 3-methylcytidine (m3C), N4 - methylcytidine (m4C), and 5-methylcytidine (m5C). Several deoxyribozymes were identified from in vitro selection, which are selective for a specific methylated cytidine isomer. The characterization of AL112, AM101, AN05, and AK104 catalysts confirmed the successful evolution of modification-specific and general deoxyribozymes that showed a broad substrate scope. In order to accelerate the DNAzymes discovery, a high throughput sequencing method (DZ-seq) was established that directly quantifies the RNA cleavage activity and cleavage site from deep sequencing data. The libraries contained information about cleavage status, cleavage site and sequence of deoxyribozymes and RNA substrate. The fraction cleaved (FC) data obtained from Dz-seq was validated for a subset of deoxyribozmes using conventional gel based kinetic assay and showed a good linear correlation (R2 = 0.91). Dz-seq possesses a great potential for the discovery of novel deoxyribozymes for the analysis of various RNA modifications in the future. The second objective of the current study was the development of structure-specific RNA labeling ribozymes. Here, we attempted to develop ribozymes that targets RNA of interest by structure-specific interaction rather than base-pairing and focused on a specific RNA G-quadruplex as the target. Two subsequent selection experiments led to the identification of the adenylyltransferase ribozymes AO10.2 and AR9. The partial characterization of these catalysts showed that A010.2 was unable to recognize intact BCL2 structure, but it turned out as the first reported trans-active ribozyme that efficiently labeled uridine in a defined substrate RNA hybridized to the ribozyme. The other ribozyme AR9 was shown to serve as a trans-active, self-labeling ribozyme that catalyzed adenylyl transferase reaction in the presence of the intact BCL2 sequence. Based on these preliminary findings, we envision that AR9 could potentially serve as a reporter RNA by self-labeling in the presence of an RNA G-quadruplex. However, both AO10.2 and AR9 still require more detailed characterization for their potential applications.},
  language  = {en}
}
@phdthesis{Toksabay2022,
  author    = {Toksabay, Sinem},
  title     = {Synthesis and on surface self assembly properties of pi extended tribenzotriquinacenes},
  doi       = {10.25972/OPUS-24573},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245734},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Tribenzotriquinacene (TBTQ) is a polycyclic aromatic framework with a particularly rigid, C3v symmetrical, bowl-shaped core bearing three mutually fused indane wings. It has been discussed as a defect center for a nanographene by Kuck and colleagues. Therefore, extended TBTQ structures are promising models for saturated defect structures in graphene and graphene like molecules and could be used to investigate the role of defects for the electronic properties of graphene. With this motivation, three different pi-extended TBTQ derivatives have been synthesized in this work. Several different Scholl reaction conditions were tried to obtain fully annulated product of hexaphenyl substituted TBTQ. The desired benzannulated TBTQ derivative could not be obtained due to unfavourable electron density in the respective positions of the molecule and increased reactivity of the bay position of the precursor. As an another method for benzannulation is the on-surface synthesis of graphene flakes and can be carried out using electron beams e.g. in a tunneling microscope (STM). According to our previous research, the parent system TBTQ and centro-methyl TBTQ on silver and gold surfaces showed that the gas phase deposition of these molecules gives rise to the formation of highly ordered two-dimensional assemblies with unique structural features. This shows the feasibility for the formation of defective graphene networks starting from the parent structures. Therefore, the same deposition technique was used to deposit Me-TBTQ(OAc)3Ph6, and investigate the molecular self-assembly properties directly on the surface of Cu (111). In summary, the substrate temperature dependent self-assembly of Me-TBTQ(OAc)3Ph6 molecules on Cu(111), shows the following evolution of orientations. At room temperature, molecules form dimers, which construct a higher-coverage honeycomb lattice. Furthermore, one of the acetyl group located in the bay positions of the TBTQ core is cleaved and the remaining two induce the metal-molecule interaction. It was presumed that by increasing the temperature to 393 K, the remaining acetyl and methyl groups would beeliminated from the molecular structure.In addition, the smaller TBTQ-Ph6 molecules preferably lie flat on Cu(111) crystal and allowing the molecules to settle into a C3-symmetry and form a dense hexagonal structure.},
  subject      = {Triquinacenderivate},
  language  = {en}
}
@phdthesis{Berger2022,
  author    = {Berger, Sarina Maria},
  title     = {Influence of Charge and Its Distribution on Biological Applications of Bis-Triarylboranes and Preliminary Investigations on H\(_2\)O\(_2\)-Cleavable Aryl Boronate Esters},
  doi       = {10.25972/OPUS-24314},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243147},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {This dissertation describes the synthesis of an unsymmetrically-substituted triarylborane. This term describes a three-coordinate boron atom that is bound to three different aromatic systems, namely 2,6-dimethylphenyl, mesityl, and 4-(N,N-dimethylamino)-2,6-dimethylphenyl. It is also demonstrated that the amine functionality can be converted with methyl triflate into an ammonium moiety. The investigation of photophysical and electrochemical properties of this compound in comparison with the non-aminated and di-aminated analogues of the triarylborane is described besides other investigations of e. g. singlet oxygen sensitization, rotational barriers, and fundamental DFT calculations. Based on these investigations, selectively mono-, bis- and tris-dimethylamino- and trimethylammonium-substituted bis-triarylborane bithiophene chromophores were synthesized and their photophysical, and electrochemical properties were investigated together with the water solubility and singlet oxygen sensitizing efficiency of the cationic compounds Cat1+, Cat2+, Cat(i)2+, and Cat3+. Comparing these properties with the results obtained for the mono-triarylboranes reveals a large influence of the bridging unit on the investigated properties of the bis-triarylboranes. In addition, the interaction of the cationic bis-triarylboranes with different polynucleotides were investigated in buffered solutions as well as the ability of these selectively charged compounds to enter and localize within organelles of human lung carcinoma and normal lung cells. All these investigations demonstrate that the number of charges and their distribution influences the interactions and staining properties as well as most of the other properties investigated. In addition, preliminary investigations on H2O2-cleavable boronate esters in the presence of stochiometric amounts of H2O2 are described for three different aryl boronate esters.},
  subject      = {Triarylborane},
  language  = {en}
}
@phdthesis{Fijalkowski2022,
  author    = {Fijalkowski, Kajetan Maciej},
  title     = {Electronic Transport in a Magnetic Topological Insulator (V,Bi,Sb)\(_2\)Te\(_3\)},
  doi       = {10.25972/OPUS-28230},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282303},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {This thesis focuses on investigating magneto-transport properties of a ferromagnetic topological insulator (V,Bi,Sb)2Te3. This material is most famously known for exhibiting the quantum anomalous Hall effect, a novel quantum state of matter that has opened up possibilities for potential applications in quantum metrology as a quantum standard of resistance, as well as for academic investigations into unusual magnetic properties and axion electrodynamics. All of those aspects are investigated in the thesis.},
  subject      = {Topologischer Isolator},
  language  = {en}
}
@phdthesis{Hofmann2022,
  author    = {Hofmann, Adrian},
  title     = {Challenges and Solution Approaches for Blockchain Technology},
  doi       = {10.25972/OPUS-28261},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282618},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The digital transformation facilitates new forms of collaboration between companies along the supply chain and between companies and consumers. Besides sharing information on centralized platforms, blockchain technology is often regarded as a potential basis for this kind of collaboration. However, there is much hype surrounding the technology due to the rising popularity of cryptocurrencies, decentralized finance (DeFi), and non-fungible tokens (NFTs). This leads to potential issues being overlooked. Therefore, this thesis aims to investigate, highlight, and address the current weaknesses of blockchain technology: Inefficient consensus, privacy, smart contract security, and scalability. First, to provide a foundation, the four key challenges are introduced, and the research objectives are defined, followed by a brief presentation of the preliminary work for this thesis. The following four parts highlight the four main problem areas of blockchain. Using big data analytics, we extracted and analyzed the blockchain data of six major blockchains to identify potential weaknesses in their consensus algorithm. To improve smart contract security, we classified smart contract functionalities to identify similarities in structure and design. The resulting taxonomy serves as a basis for future standardization efforts for security-relevant features, such as safe math functions and oracle services. To challenge privacy assumptions, we researched consortium blockchains from an adversary role. We chose four blockchains with misconfigured nodes and extracted as much information from those nodes as possible. Finally, we compared scalability solutions for blockchain applications and developed a decision process that serves as a guideline to improve the scalability of their applications. Building on the scalability framework, we showcase three potential applications for blockchain technology. First, we develop a token-based approach for inter-company value stream mapping. By only relying on simple tokens instead of complex smart-contracts, the computational load on the network is expected to be much lower compared to other solutions. The following two solutions use offloading transactions and computations from the main blockchain. The first approach uses secure multiparty computation to offload the matching of supply and demand for manufacturing capacities to a trustless network. The transaction is written to the main blockchain only after the match is made. The second approach uses the concept of payment channel networks to enable high-frequency bidirectional micropayments for WiFi sharing. The host gets paid for every second of data usage through an off-chain channel. The full payment is only written to the blockchain after the connection to the client gets terminated. Finally, the thesis concludes by briefly summarizing and discussing the results and providing avenues for further research.},
  subject      = {Blockchain},
  language  = {en}
}
@phdthesis{Uenzelmann2022,
  author    = {{\"U}nzelmann, Maximilian},
  title     = {Interplay of Inversion Symmetry Breaking and Spin-Orbit Coupling - From the Rashba Effect to Weyl Semimetals},
  doi       = {10.25972/OPUS-28310},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283104},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Breaking inversion symmetry in crystalline solids enables the formation of spin-polarized electronic states by spin-orbit coupling without the need for magnetism. A variety of interesting physical phenomena related to this effect have been intensively investigated in recent years, including the Rashba effect, topological insulators and Weyl semimetals. In this work, the interplay of inversion symmetry breaking and spin-orbit coupling and, in particular their general influence on the character of electronic states, i.e., on the spin and orbital degrees of freedom, is investigated experimentally. Two different types of suitable model systems are studied: two-dimensional surface states for which the Rashba effect arises from the inherently broken inversion symmetry at the surface, and a Weyl semimetal, for which inversion symmetry is broken in the three-dimensional crystal structure. Angle-resolved photoelectron spectroscopy provides momentum-resolved access to the spin polarization and the orbital composition of electronic states by means of photoelectron spin detection and dichroism with polarized light. The experimental results shown in this work are also complemented and supported by ab-initio density functional theory calculations and simple model considerations. Altogether, it is shown that the breaking of inversion symmetry has a decisive influence on the Bloch wave function, namely, the formation of an orbital angular momentum. This mechanism is, in turn, of fundamental importance both for the physics of the surface Rashba effect and the topology of the Weyl semimetal TaAs.},
  subject      = {Rashba-Effekt},
  language  = {en}
}
@phdthesis{Dorin2022,
  author    = {Dorin, Michael},
  title     = {The Relationship Between Software Complicacy and Software Reliability},
  doi       = {10.25972/OPUS-28308},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283085},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {An enduring engineering problem is the creation of unreliable software leading to unreliable systems. One reason for this is source code is written in a complicated manner making it too hard for humans to review and understand. Complicated code leads to other issues beyond dependability, such as expanded development efforts and ongoing difficulties with maintenance, ultimately costing developers and users more money. There are many ideas regarding where blame lies in the reation of buggy and unreliable systems. One prevalent idea is the selected life cycle model is to blame. The oft-maligned "waterfall" life cycle model is a particularly popular recipient of blame. In response, many organizations changed their life cycle model in hopes of addressing these issues. Agile life cycle models have become very popular, and they promote communication between team members and end users. In theory, this communication leads to fewer misunderstandings and should lead to less complicated and more reliable code. Changing the life cycle model can indeed address communications ssues, which can resolve many problems with understanding requirements. However, most life cycle models do not specifically address coding practices or software architecture. Since lifecycle models do not address the structure of the code, they are often ineffective at addressing problems related to code complicacy. This dissertation answers several research questions concerning software complicacy, beginning with an investigation of traditional metrics and static analysis to evaluate their usefulness as measurement tools. This dissertation also establishes a new concept in applied linguistics by creating a measurement of software complicacy based on linguistic economy. Linguistic economy describes the efficiencies of speech, and this thesis shows the applicability of linguistic economy to software. Embedded in each topic is a discussion of the ramifications of overly complicated software, including the relationship of complicacy to software faults. Image recognition using machine learning is also investigated as a potential method of identifying problematic source code. The central part of the work focuses on analyzing the source code of hundreds of different projects from different areas. A static analysis was performed on the source code of each project, and traditional software metrics were calculated. Programs were also analyzed using techniques developed by linguists to measure expression and statement complicacy and identifier complicacy. Professional software engineers were also directly surveyed to understand mainstream perspectives. This work shows it is possible to use traditional metrics as indicators of potential project bugginess. This work also discovered it is possible to use image recognition to identify problematic pieces of source code. Finally, this work discovered it is possible to use linguistic methods to determine which statements and expressions are least desirable and more complicated for programmers. This work's principle conclusion is that there are multiple ways to discover traits indicating a project or a piece of source code has characteristics of being buggy. Traditional metrics and static analysis can be used to gain some understanding of software complicacy and bugginess potential. Linguistic economy demonstrates a new tool for measuring software complicacy, and machine learning can predict where bugs may lie in source code. The significant implication of this work is developers can recognize when a project is becoming buggy and take practical steps to avoid creating buggy projects.},
  subject      = {Softwareentwicklung},
  language  = {en}
}
@phdthesis{VermaFuehring2022,
  author    = {Verma-F{\"u}hring, Raoul},
  title     = {Die Trabekulopunktion als Pr{\"a}diktiver Test f{\"u}r den Erfolg der Ab Interno Trabekulektomie im Schweineaugenmodell},
  doi       = {10.25972/OPUS-28263},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282633},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {To investigate trabeculopuncture (TP) for predicting the outcome of ab interno trabeculectomy (AIT). Ex vivo porcine anterior segments were perfused and sequentially underwent two procedures, TP and AIT. We concluded that a 10\% reduction in IOP after TP can be used to predict the success (>20\% IOP decrease) of AIT in porcine eyes. As porcine eyes share many similarities with human eyes, our findings may have implications on the validity of this test as a predictor for surgical outcomes of AITs in humans.},
  subject      = {Glaukom},
  language  = {en}
}
@phdthesis{Schorscher2022,
  author    = {Schorscher, Nora},
  title     = {Systematic literature review on lessons learnt from terrorist attacks with a focus on pre-hospital and in-hospital management},
  doi       = {10.25972/OPUS-28213},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282133},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Purpose: The threat of national and international terrorism remains high. Preparation is the key requirement for the resilience of hospitals and out-of-hospital rescue forces. The scientific evidence for defining medical and tactical strategies often feeds on the analysis of real incidents and the lessons learned derived from them. This systematic review of the literature aims to identify and systematically report lessons learned from terrorist attacks since 2001. Methods: PubMed was used as a database using predefined search strategies and eligibility criteria. All countries that are part of the Organization for Economic Cooperation and Development (OECD) were included. The time frame was set between 2001 and 2018. Results: 68 articles were included in the review. From these, 616 lessons learned were extracted and summarized into 15 categories. The data shows that despite the difference in attacks, countries, and casualties involved, many of the lessons learned are similar. We also found that the pattern of lessons learned is repeated continuously over the time period studied. Conclusions: The lessons from terrorist attacks since 2001 follow a certain pattern and remained constant over time. Therefore, it seems to be more accurate to talk about lessons identified rather than lessons learned. To save as many victims as possible, protect rescue forces from harm, and to prepare hospitals at the best possible level it is important to implement the lessons identified in training and preparation.},
  subject      = {Terror},
  language  = {en}
}
@phdthesis{Sahiti2022,
  author    = {Sahiti, Floran},
  title     = {Myocardial Work - Application and Clinical Characterization of a New Echocardiographic Tool},
  doi       = {10.25972/OPUS-28226},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282261},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {1 Summary Left ventricular (LV) ejection fraction (EF) and global longitudinal strain (GLS) are the most commonly used measures of LV function. Yet, they are highly dependent on loading conditions since higher afterload yields lower systolic deformation and thereby a lower LVEF and GLS - despite presumably unchanged LV myocardial contractile strength. Invasive pressure-volume loop measurements represent the reference standard to assess LV function, also considering loading conditions. However, this procedure cannot be used in serial investigations or large sample populations due to its invasive nature. The novel concept of echocardiography-derived assessment of myocardial work (MyW) is based on LV pressure-strain loops, may be a valuable alternative to overcome these challenges, and may also be used with relative ease in large populations. As MyW also accounts for afterload, it is considered less load-dependent than LVEF and GLS. The current PhD work addresses the application and clinical characterization of MyW, an innovative echocardiographic tool. As the method is new, we focused on four main topics: (a) To establish reference values for MyW indices, i.e., Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), and Global Work Efficiency (GWE); we addressed a wide age range and evaluated the association of MyW indices with age, sex and other clinical and echocardiography parameters in apparently cardiovascular healthy individuals. (b) To investigate the impact of cardiovascular (CV) risk factors on MyW indices and characterize the severity of subclinical LV deterioration in the general population. (c) To assess the association of the LV geometry, i.e., LV mass and dimensions, with MyW indices. (d) To evaluate in-hospital dynamics of MyW indices in patients hospitalized for acute heart failure (AHF). For the PhD thesis, we could make use of two larger cohorts: The STAAB population-based cohort study prospectively recruited and phenotyped a representative sample (5,000 individuals) of the general population of the City of W{\"u}rzburg, aged 30-79 years and free from symptomatic heart failure at the time of inclusion. We focused on the first half of the study sample (n=2473 individuals), which fulfilled the anticipated strata regarding age and sex. The Acute Heart Failure (AHF) Registry is a prospective clinical registry recruiting and phenotyping consecutive patients admitted for decompensated AHF to the Department of Medicine I, University Hospital W{\"u}rzburg, and observing the natural course of the disease. The AHF Registry focuses on the pathophysiological understanding, particularly in relation to the early phase after cardiac decompensation, with the aim to improve diagnosis and better-tailored treatment of patients with AHF. For the current study, we concentrated on patients who provided pairs of echocardiograms acquired early after index hospital admission and prior to discharge. The main findings of the PhD thesis were: From the STAAB cohort study, we determined the feasibility of large-scale MyW derivation and the accuracy of the method. We established reference values for MyW indices based on 779 analyzable, apparently healthy participants (mean age 49 ± 10 years, 59\% women), who were in sinus rhythm, free from CV risk factors or CV disease, and had no significant LV valve disease. Apart from GWI, there were no associations of other MyW indices with sex. Further, we found a disparate association with age, where MyW showed stable values until the age of 45 years, with an upward shift occurring beyond the age of 45. A higher age decade was associated with higher GWW and lower GWE, respectively. MyW indices only correlated weakly with common echocardiographic parameters, suggesting that MyW may add incremental information to clinically established parameters. Further analyses from the STAAB cohort study contributed to a better understanding of the impact of CV risk factors on MyW indices and the association of LV geometry with LV performance. We demonstrated that CV risk factors impacted selectively on GCW and GWW. Hypertension appears to profoundly compromise the work of the myocardium, in particular, by increasing both GCW and GWW. The LV in hypertension seems to operate at a higher energy level yet lower efficiency. Other classical CV risk factors (Diabetes mellitus, Obesity, Dyslipidemia, Smoking) - independent of blood pressure - impacted consistently and adversely on GCW but did not affect GWW. Further, all CV risk factors affected GWE adversely. We observed that any deviation from a normal LV geometric profile was associated with alterations on MyW. Of note, MyW was sensitive to early changes in LV mass and dimensions. Individuals with normal LV geometry yet established arterial hypertension exhibited a MyW pattern that is typically found in LV hypertrophy. Therefore, such a pattern might serve as an early sign of myocardial damage in hypertensive heart disease and might aid in risk stratification and primary prevention. From the AHF Registry, we selected individuals with serial in-hospital echocardiograms and described in-hospital changes in myocardial performance during recompensation. In patients presenting with a reduced ejection fraction (HFrEF), decreasing N-terminal pro-natriuretic peptide (NT-proBNP) levels as a surrogate of successful recompensation were associated with an improvement in GCW and GWI and consecutively in GWE. In contrast, in patients presenting with a preserved ejection fraction (HFpEF), there was no significant change in GCW and GWI. However, unsuccessful recompensation, i.e., no change or an increase in NT-proBNP levels, was associated with an increase in GWW. This suggests a differential myocardial response to de- and recompensation depending on the HF phenotype. Further, GWW as a surrogate of inappropriate LV energy consumption was elevated in all patients with AHF (compared to reference values) and was not associated with conventional markers as LVEF or NT-proBNP. In an exploratory analysis, GWW predicted the risk of death or rehospitalization within six months after discharge. Hence, GWW might carry incremental information beyond conventional markers of HF severity.},
  language  = {en}
}
@phdthesis{Selby2022,
  author    = {Selby, Joshua},
  title     = {Design and Chiroptical Properties of Chirally Substituted Indolenine Squaraine Mono-, Oligo-, and Polymers},
  doi       = {10.25972/OPUS-28206},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282067},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {A series of monomeric chirally substituted indolenine squaraine monomers were successfully synthesized and utilized for the construction of various oligo- and polymers, in order to study their chiroptical properties in terms of exciton chirality. The quaternary carbon atom at the 3-position of the indolenine subunit, as well as the alkyl side chain attached to the indolenine nitrogen were selected as the most suitable site for chiral functionalization. For the C(3)-chiral derivatives, two synthetic routes depending on the desired substitution at the stereogenic center were established. The chiral side chains were prepared via Evans asymmetric alkylation where the resulting branching point at the 2 position constituted the chiral center. While the chiral substitution only had minor effects on the linear optical properties and geometric structure of the chromophore, all compounds exhibited a distinct and measurable CD signal that correlated with the distance of the chiral center to the central chromophore. Polymers bearing chiral side chains exhibited a solvent- and temperature-dependent helix-coil equilibrium, which was influenced by the type of side chain used. CD spectroscopy revealed the helical conformation to possess a preferred twist sense, and temperature-dependent measurements showed the degree of homohelicity to be nearly complete in certain cases. Furthermore, a CPL signal was able to be obtained for the helical conformer of one polymer. Various (co)oligo- and polymers comprising the C(3)-chiral monomers only displayed a solvent-independent J-type absorption behavior and thus did not form helical conformations in solution. CD spectroscopy revealed a solvent-dependent adoption of quasi-enantiomeric conformers, which was elucidated by quantum chemical TDDFT calculations.},
  subject      = {Squaraine},
  language  = {en}
}
@phdthesis{Freimann2022,
  author    = {Freimann, Andreas},
  title     = {Efficient Communication in Networks of Small Low Earth Orbit Satellites and Ground Stations},
  isbn      = {978-3-945459-41-6},
  doi       = {10.25972/OPUS-28052},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280521},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {With the miniaturization of satellites a fundamental change took place in the space industry. Instead of single big monolithic satellites nowadays more and more systems are envisaged consisting of a number of small satellites to form cooperating systems in space. The lower costs for development and launch as well as the spatial distribution of these systems enable the implementation of new scientific missions and commercial services. With this paradigm shift new challenges constantly emerge for satellite developers, particularly in the area of wireless communication systems and network protocols. Satellites in low Earth orbits and ground stations form dynamic space-terrestrial networks. The characteristics of these networks differ fundamentally from those of other networks. The resulting challenges with regard to communication system design, system analysis, packet forwarding, routing and medium access control as well as challenges concerning the reliability and efficiency of wireless communication links are addressed in this thesis. The physical modeling of space-terrestrial networks is addressed by analyzing existing satellite systems and communication devices, by evaluating measurements and by implementing a simulator for space-terrestrial networks. The resulting system and channel models were used as a basis for the prediction of the dynamic network topologies, link properties and channel interference. These predictions allowed for the implementation of efficient routing and medium access control schemes for space-terrestrial networks. Further, the implementation and utilization of software-defined ground stations is addressed, and a data upload scheme for the operation of small satellite formations is presented.},
  subject      = {Satellitenfunk},
  language  = {en}
}
@phdthesis{Langejahn2022,
  author    = {Langejahn, Marcus},
  title     = {Hard X-ray Properties of Relativistically Beamed Jets from Radio- and Gamma-Ray-Bright Blazars},
  doi       = {10.25972/OPUS-28200},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282009},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In this work I characterize the hard X-ray properties of blazars, active galactic nuclei with highly beamed emission, which are notoriously hard to detect in this energy range. I employ pre-defined samples of beamed AGN: the radio-selected MOJAVE and TANAMI samples, as well as the most recent gamma-ray-selected Fermi/LAT 4LAC catalog. The hard X-ray data is extracted from the 105-month all-sky survey maps of the Swift/BAT (Burst Alert Telescope) in the energy band of 20 keV to 100 keV. A great majority of both the MOJAVE and TANAMI samples are significantly detected, with signal-to noise ratios of the sources often just below the X-ray catalog signal thresholds. All blazar sub-types (FSRQs, BL Lacs) and radio galaxies show characteristic ranges of X-ray flux, luminosity, and photon index. Their properties are correlated with the corresponding SED's shape / peak frequency. The LogN-LogS distributions of the samples show a scarcity of blazars in the middle and lower X-ray flux range, indicating differing evolutionary paths between radio and X-ray emission, which is also suggested by the corresponding luminosity functions. Compared to the radio samples, the 4LAC sources are on average significantly less bright in the BAT band since this range often coincides with the spectral gap region between the two big SED emission bumps. Also, the spectral shapes differ notably, especially for the sub-type of BL Lacs. Using the parameter space of X-ray and gamma-ray photon indices, 35 blazar candidate sources can be assigned to either the FSRQ or BL Lac type with high certainty. The reason why many blazars are weak in this energy band can be traced back to a number of factors: the selection bias of the initial sample, differential evolution of the X-rays and the wavelengths in which the sample is defined, and the limited sensitivity of the observing instruments.},
  subject      = {Aktiver galaktischer Kern},
  language  = {en}
}
@phdthesis{Gerbershagen2022,
  author    = {Gerbershagen, Marius},
  title     = {Quantum information and the emergence of spacetime in the AdS/CFT correspondence},
  doi       = {10.25972/OPUS-28199},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281997},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {This thesis studies connections between quantum information measures and geometric features of spacetimes within the AdS/CFT correspondence. These studies are motivated by the idea that spacetime can be thought of as an effect emerging from an underlying entanglement structure in the AdS/CFT correspondence. In particular, I study generalized entanglement measures in two-dimensional conformal field theories and their holographic duals. Unlike the ordinary entanglement entropy of a spatial subregion typically used in the AdS/CFT context, the generalization considered here measures correlations between different fields as well as between spatial degrees of freedom. I present a new gauge invariant definition of the generalized entanglement entropy applicable to both mixed and pure states as well as explicit results for thermal states of the S_N-orbifold theory of the D1/D5 system. Along the way, I develop computation techniques for conformal blocks on the torus and apply them to the calculation of the ordinary entanglement entropy for large central charge CFTs at finite size and finite temperature. The generalized Ryu-Takayanagi formula arising from these studies provides further support for the idea that entanglement and geometry are intrinsically linked in AdS/CFT. The results show that the holographic dual to the generalized entanglement entropy given by the length of a geodesic winding around black hole horizons or naked singularities probes subregions of spacetime that are inaccessible to Ryu-Takayanagi surfaces, thereby solving the puzzle of how these features of the spacetime are encoded in the boundary theory. Furthermore, I investigate quantum circuits embedded in two-dimensional conformal field theories as well as computational complexity measures therein. These investigations are motivated by conjectures relating computational complexity in conformal field theories to geometric features of black hole geometries. In this thesis, I study quantum circuits built up from conformal transformations. I investigate examples of computational complexity measures in these circuits related to geometric actions on coadjoint orbits of the Virasoro group and to the Fubini-Study metric. I then work out relations between these computational complexity measures and the dual gravitational theory. Moreover, I construct a bulk dual to the circuits in consideration and use this construction to study geometric realizations of computational complexity measures from first principles. The results of this part on the one hand rule out some possibilities for dual realizations of computational complexity in two-dimensional CFTs put forward in previous work while on the other hand providing a new robust dual realization of a computational complexity measure based on the Fubini-Study distance.},
  subject      = {AdS-CFT-Korrespondenz},
  language  = {en}
}
@phdthesis{Madeira2022,
  author    = {Madeira, Octavia},
  title     = {The Human-Experimental Virtual Elevated Plus-Maze as an Anxiety Model},
  doi       = {10.25972/OPUS-28147},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281478},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Anxiety research is one of the major psychological research domains and looks back on decades of research activity. Traditionally, novel theories and approaches are tested utilizing animal models. One way to study inherent anxiety in rodents is the elevated plus-maze (EPM). The EPM is a plus-shaped platform with two closed, i.e., walled, arms and two open unwalled arms. If given the opportunity to freely explore the apparatus, rodents instinctively avoid the open arms to protect themselves from predators. Hence, they spent less time on open and more time on closed arms, which is behaviorally associated with general anxiety. In the course of the pharmacological validation, it was found that this exploratory pattern can be reversed by anxiolytic substances, e.g., benzodiazepines, or potentiated by anxiogenics. One of the significant advantages of the EPM is that no prior training session is required in contrast to conditioning studies, thus allowing to observe natural behavior. Therefore, together with the economic and uncomplicated setup, the EPM has become a standard preclinical rodent anxiety test over the decades. In order to validate these rodent anxiety tests, there have recently been attempts to retranslate them to humans. A paramount of cross-species validation is not only the simple transferability of these animal tests but also the observation of anxiety behaviors that are evolutionarily conserved across species. Accordingly, it could be possible to conclude various factors associated with the etiology and maintenance of anxiety disorders in humans. So far, convincing translations of the EPM to humans are still lacking. For that reason, the primary aim of this dissertation is to retranslate the EPM throughout three studies and to evaluate cross-species validity critically. Secondly, the undertaken studies are set out to observe ambulatory activity equivalent to rodent EPM behavior, i.e., open arm avoidance. Thirdly, the undertaken studies aimed to assess the extent to which trait anxiety influences human exploratory activity on the platform to associate it with the assumption that rodent EPM-behavior is a reflection of general anxiety. Finally, virtual reality (VR) was the method of choice to maintain the economic advantage and adjust the EPM size to humans. Study 1 (N = 30) was set up to directly transfer the rodent EPM regarding test design and experimental procedure using a Computer Automatic Virtual Environment (CAVE). The results revealed that humans unlike rodents display a general open arms approach during free exploration. However, open arm avoidance was associated with high trait anxiety and acrophobia (fear of height), which was initially assessed as a control variable due to the virtual platform height. Regression analyses and subjective anxiety ratings hinted at a more significant influence of acrophobia on open arm avoidance. In addition, it was assumed that the open arms approach might have resulted from claustrophobic tendencies experienced in the closed arms due to the high walls. Study 2 (N = 61) sought to differentiate the influence of trait anxiety and acrophobia and adapt the virtual EPM to humans. Therefore, parts of the platform held a semi-transparent grid-floor texture, and the wall height on the closed arms was reduced to standard handrail level. Moreover, participants were priorly screened to exclude clinically significant levels of acrophobia, claustrophobia, and agoraphobia. The data on general exploratory activity showed no arm preference. Regression analyses confirmed that acrophobia is related to open arm avoidance, corroborating the finding of Study 1. Surprisingly, for trait anxiety, the result of Study 1 could not be replicated. Instead, for trait anxiety, no significant effect was found indicating that predominantly fear of heights shapes human EPM behavior even on a subclinical stage. In Study 3 (N = 57), the EPM was embedded into a city setting to 1) create a more natural human environment and 2) eliminate height. Furthermore, a head-mounted display was utilized for VR presentation, and arousal ratings were introduced. Participants were screened for high and low levels of trait anxiety and agoraphobia, and claustrophobia. Replicating the findings of Study 2, no difference in open and closed arm activity was observed, and no effect was found in relationship with trait anxiety. The data on anxiety ratings and claustrophobia suggest a positive correlation indicating that in this city EPM, claustrophobic tendencies might play a role in closed arm avoidance. In summary, this thesis added valuable insights into the retranslation of a well-established standard anxiety test used in rodents. However, it also majorly challenges current findings on the cross-species validity of the EPM. Various explanatory models for the results are critically discussed and associated with clinical implications concerning future research.},
  subject      = {Virtuelle Realit{\"a}t},
  language  = {en}
}
@phdthesis{JimenezMartin2022,
  author    = {Jim{\´e}nez Mart{\´i}n, Ovidio Manuel},
  title     = {Analysis of MYCN and MAX alterations in Wilms Tumor},
  doi       = {10.25972/OPUS-24291},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242919},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Wilms tumor (WT) is the most common renal tumor in childhood. Among others, MYCN copy number gain and MYCN P44L and MAX R60Q mutations have been identified in WT. The proto-oncogene MYCN encodes a transcription factor that requires dimerization with MAX to activate transcription of numerous target genes. MYCN gain has been associated with adverse prognosis. The MYCN P44L and MAX R60Q mutations, located in either the transactivating or basic helix-loop-helix domain, respectively, are predicted to be damaging by different pathogenicity prediction tools. These mutations have been reported in several other cancers and remain to be functionally characterized. In order to further describe these events in WT, we screened both mutations in a large cohort of unselected WT patients, to check for an association of the mutation status with certain histological or clinical features. MYCN P44L and MAX R60Q revealed frequencies of 3 \% and 0.9 \% and also were significantly associated to higher risk of relapse and metastasis, respectively. Furthermore, to get a better understanding of the MAX mutational landscape in WT, over 100 WT cases were analyzed by Sanger sequencing to identify other eventual MAX alterations in its coding sequence. R60Q remained the only MAX CDS alteration described in WT to date. To analyze the potential functional consequences of these mutations, we used a doxycycline-inducible system to overexpress each mutant in HEK293 cells. This biochemical characterization identified a reduced transcriptional activation potential for MAX R60Q, while the MYCN P44L mutation did not change activation potential or protein stability. The protein interactome of N-MYC-P44L was likewise not altered as shown by mass spectrometric analyses of purified N-MYC complexes. However, we could identify a number of novel N-MYC partner proteins, several of these known for their oncogenic potential. Their correlated expression in WT samples suggested a role in WT oncogenesis and they expand the range of potential biomarkers for WT stratification and targeting, especially for high-risk WT.},
  subject      = {Nephroblastom},
  language  = {en}
}
@phdthesis{GraetzgebDittmann2022,
  author    = {Graetz [geb. Dittmann], Jonas},
  title     = {X-Ray Dark-Field Tensor Tomography : a Hitchhiker's Guide to Tomographic Reconstruction and Talbot Imaging},
  doi       = {10.25972/OPUS-28143},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281437},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {X-ray dark-field imaging allows to resolve the conflict between the demand for centimeter scaled fields of view and the spatial resolution required for the characterization of fibrous materials structured on the micrometer scale. It draws on the ability of X-ray Talbot interferometers to provide full field images of a sample's ultra small angle scattering properties, bridging a gap of multiple orders of magnitude between the imaging resolution and the contrasted structure scale. The correspondence between shape anisotropy and oriented scattering thereby allows to infer orientations within a sample's microstructure below the imaging resolution. First demonstrations have shown the general feasibility of doing so in a tomographic fashion, based on various heuristic signal models and reconstruction approaches. Here, both a verified model of the signal anisotropy and a reconstruction technique practicable for general imaging geometries and large tensor valued volumes is developed based on in-depth reviews of dark-field imaging and tomographic reconstruction techniques. To this end, a wide interdisciplinary field of imaging and reconstruction methodologies is revisited. To begin with, a novel introduction to the mathematical description of perspective projections provides essential insights into the relations between the tangible real space properties of cone beam imaging geometries and their technically relevant description in terms of homogeneous coordinates and projection matrices. Based on these fundamentals, a novel auto-calibration approach is developed, facilitating the practical determination of perspective imaging geometries with minimal experimental constraints. A corresponding generalized formulation of the widely employed Feldkamp algorithm is given, allowing fast and flexible volume reconstructions from arbitrary tomographic imaging geometries. Iterative reconstruction techniques are likewise introduced for general projection geometries, with a particular focus on the efficient evaluation of the forward problem associated with tomographic imaging. A highly performant 3D generalization of Joseph's classic linearly interpolating ray casting algorithm is developed to this end and compared to typical alternatives. With regard to the anisotropic imaging modality required for tensor tomography, X-ray dark-field contrast is extensively reviewed. Previous literature is brought into a joint context and nomenclature and supplemented by original work completing a consistent picture of the theory of dark-field origination. Key results are explicitly validated by experimental data with a special focus on tomography as well as the properties of anisotropic fibrous scatterers. In order to address the pronounced susceptibility of interferometric images to subtle mechanical imprecisions, an efficient optimization based evaluation strategy for the raw data provided by Talbot interferometers is developed. Finally, the fitness of linear tensor models with respect to the derived anisotropy properties of dark-field contrast is evaluated, and an iterative scheme for the reconstruction of tensor valued volumes from projection images is proposed. The derived methods are efficiently implemented and applied to fiber reinforced plastic samples, imaged at the ID19 imaging beamline of the European Synchrotron Radiation Facility. The results represent unprecedented demonstrations of X-ray dark-field tensor tomography at a field of view of 3-4cm, revealing local fiber orientations of both complex shaped and low-contrast samples at a spatial resolution of 0.1mm in 3D. The results are confirmed by an independent micro CT based fiber analysis.},
  subject      = {Dreidimensionale Rekonstruktion},
  language  = {en}
}
@phdthesis{MikaGospodorz2022,
  author    = {Mika-Gospodorz, Bozena},
  title     = {Development and application of bioinformatics tools for analysis of dual RNA-seq experiments},
  doi       = {10.25972/OPUS-28126},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281264},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Dual RNA-seq captures both host and pathogen transcriptomes at the site of infection, facilitating an exploration of processes that play an essential role in pathogenesis and the host defense. This work presents an application of this technique to explore processes occurring during the infection of the human endothelial cells with two clinical isolates of Orientia tsutsugamushi (Ot) — the causative agent of scrub typhus. Combining comparative genomics, transcriptomics, and proteomics, we investigated the transcriptional architecture of Ot and identified non-coding RNAs, operon structures, and widespread antisense transcription, that may have a role in regulation of repetitive genes that are abundant in the Ot genome. In addition, the comparative analysis of bacterial and eukaryotic transcriptomes allowed us to investigate factors that drive the difference in virulence between Karp and UT176 and the host response to these two Ot strains. The host and pathogen transcriptional profiles in each dual RNA-seq study are obtained in‑silico by adopting tools developed for RNA-seq data analysis. The Dualrnaseq pipeline presented in the second part of this work is the first publicly available, highly reproducible, scalable, and user‑friendly workflow developed for processing dual RNA‑seq data of any eukaryotic and bacterial organisms with a reference genome and annotation. It provides three mapping and quantification strategies: (i) alignment-based mapping of reads onto the chimeric genome with STAR followed by counting of uniquely mapped reads with HTSeq; (ii) a fast transcriptome quantification method handling multi‑mapped reads (Salmon with Selective Alignment); (iii) and Salmon alignment-based mode which uses a STAR‑derived alignment combined with Salmon quantification. Performing an initial benchmark analysis of the employed methods we provided recommendations ensuring accurate estimation of host and pathogen transcript expression.},
  subject      = {Transkriptomanalyse},
  language  = {en}
}
@phdthesis{Dirscherl2022,
  author    = {Dirscherl, Mariel Christina},
  title     = {Remote Sensing of Supraglacial Lake Dynamics in Antarctica - Exploiting Methods from Artificial Intelligence for Derivation of Antarctic Supraglacial Lake Extents in Multi-Sensor Remote Sensing Data},
  doi       = {10.25972/OPUS-27950},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-279505},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {With accelerating global climate change, the Antarctic Ice Sheet is exposed to increasing ice dynamic change. During 1992 and 2017, Antarctica contributed ~7.6 mm to global sea-level-rise mainly due to ocean thermal forcing along West Antarctica and atmospheric warming along the Antarctic Peninsula (API). Together, these processes caused the progressive retreat of glaciers and ice shelves and weakened their efficient buttressing force causing widespread ice flow accelerations. Holding ~91\% of the global ice mass and 57.3 m of sea-level-equivalent, the Antarctic Ice Sheet is by far the largest potential contributor to future sea-level-rise. Despite the improved understanding of Antarctic ice dynamics, the future of Antarctica remains difficult to predict with its contribution to global sea-level-rise representing the largest uncertainty in current projections. Given that recent studies point towards atmospheric warming and melt intensification to become a dominant driver for future Antarctic ice mass loss, the monitoring of supraglacial lakes and their impacts on ice dynamics is of utmost importance. In this regard, recent progress in Earth Observation provides an abundance of high-resolution optical and Synthetic Aperture Radar (SAR) satellite data at unprecedented spatial and temporal coverage and greatly supports the monitoring of the Antarctic continent where ground-based mapping efforts are difficult to perform. As an automated mapping technique for supraglacial lake extent delineation in optical and SAR satellite imagery as well as a pan-Antarctic inventory of Antarctic supraglacial lakes at high spatial and temporal resolution is entirely missing, this thesis aims to advance the understanding of Antarctic surface hydrology through exploitation of spaceborne remote sensing. In particular, a detailed literature review on spaceborne remote sensing of Antarctic supraglacial lakes identified several research gaps including the lack of (1) an automated mapping technique for optical or SAR satellite data that is transferable in space and time, (2) high-resolution supraglacial lake extent mappings at intra-annual and inter-annual temporal resolution and (3) large-scale mapping efforts across the entire Antarctic continent. In addition, past method developments were found to be restricted to purely visual, manual or semi-automated mapping techniques hindering their application to multi-temporal satellite imagery at large-scale. In this context, the development of automated mapping techniques was mainly limited by sensor-specific characteristics including the similar appearance of supraglacial lakes and other ice sheet surface features in optical or SAR data, the varying temporal signature of supraglacial lakes throughout the year as well as effects such as speckle noise and wind roughening in SAR data or cloud coverage in optical data. To overcome these limitations, this thesis exploits methods from artificial intelligence and big data processing for development of an automated processing chain for supraglacial lake extent delineation in Sentinel-1 SAR and optical Sentinel-2 satellite imagery. The combination of both sensor types enabled to capture both surface and subsurface lakes as well as to acquire data during cloud cover or wind roughening of lakes. For Sentinel-1, a deep convolutional neural network based on residual U-Net was trained on the basis of 21,200 labeled Sentinel-1 SAR image patches covering 13 Antarctic regions. Similarly, optical Sentinel-2 data were collected over 14 Antarctic regions and used for training of a Random Forest classifier. Optical and SAR classification products were combined through decision-level fusion at bi-weekly temporal scale and unprecedented 10 m spatial resolution. Finally, the method was implemented as part of DLR's High-Performance Computing infrastructure allowing for an automated processing of large amounts of data including all required pre- and postprocessing steps. The results of an accuracy assessment over independent test scenes highlighted the functionality of the classifiers returning accuracies of 93\% and 95\% for supraglacial lakes in Sentinel-1 and Sentinel-2 satellite imagery, respectively. Exploiting the full archive of Sentinel-1 and Sentinel-2, the developed framework for the first time enabled the monitoring of seasonal characteristics of Antarctic supraglacial lakes over six major ice shelves in 2015-2021. In particular, the results for API ice shelves revealed low lake coverage during 2015-2018 and particularly high lake coverage during the 2019-2020 and 2020-2021 melting seasons. On the contrary, East Antarctic ice shelves were characterized by high lake coverage during 2016-2019 and extremely low lake coverage during the 2020-2021 melting season. Over all six investigated ice shelves, the development of drainage systems was revealed highlighting an increased risk for ice shelf instability. Through statistical correlation analysis with climate data at varying time lags as well as annual data on Southern Hemisphere atmospheric modes, environmental drivers for meltwater ponding were revealed. In addition, the influence of the local glaciological setting was investigated through computation of annual recurrence times of lakes. Over both ice sheet regions, the complex interplay between local, regional and large-scale environmental drivers was found to control supraglacial lake formation despite local to regional discrepancies, as revealed through pixel-based correlation analysis. Local control factors included the ice surface topography, the ice shelf geometry, the presence of low-albedo features as well as a reduced firn air content and were found to exert strong control on lake distribution. On the other hand, regional controls on lake evolution were revealed to be the amount of incoming solar radiation, air temperature and wind occurrence. While foehn winds were found to dictate lake evolution over the API, katabatic winds influenced lake ponding in East Antarctica. Furthermore, the regional near-surface climate was shown to be driven by large-scale atmospheric modes and teleconnections with the tropics. Overall, the results highlight that similar driving factors control supraglacial lake formation on the API and EAIS pointing towards their transferability to other Antarctic regions.},
  subject      = {Optische Fernerkundung},
  language  = {en}
}
@phdthesis{Karch2022,
  author    = {Karch, Katharina},
  title     = {Mapping and Neutralization of Antibodies against Neurofascin, Contactin 1, Contactin associated protein 1 and Cortactin},
  doi       = {10.25972/OPUS-28022},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280223},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Immune-mediated polyneuropathies like chronic inflammatory demyelinating polyradiculoneuropathy or Guillain-Barr{\´e} syndrome are rare diseases of the peripheral nervous system. A subgroup of patients harbors autoantibodies against nodal or paranodal antigens, associated with a distinct phenotype and treatment response. In a part of patients with pathologic paranodal or nodal immunoreactivity the autoantigens remain difficult or impossible to determine owing to limitations of the used detection approach - usually ELISAs (enzyme-linked-immunosorbent-assays) - and incomplete knowledge of the possible autoantigens. Due to their high-throughput, low sample consumption and high sensitivity as well as the possibility to display many putative nodal and paranodal autoantigens simultaneously, peptide microarray-based approaches are prime candidates for the discovery of novel autoantigens, point-of-care diagnostics and, in addition, monitoring of pathologic autoimmune response. Current applications of peptide microarrays are however limited by high false-positive rates and the associated need for detailed follow-up studies and validation. Here, robust peptide microarray-based detection of antibodies and the efficient validation of binding signals by on-chip neutralization is demonstrated. First, autoantigens were displayed as overlapping peptide libraries in microarray format. Copies of the biochips were used for the fine mapping of antibody epitopes. Next, binding signals were validated by antibody neutralization in solution. Since neutralizing peptides are obtained in the process of microarray fabrications, neither throughput nor costs are significantly altered. Similar in-situ validation approaches could contribute to future autoantibody characterization and detection methods as well as to therapeutic research. Areas of application could be expanded to any autoimmune-mediated neurological disease as a long-term vision.},
  subject      = {Microarray},
  language  = {en}
}
@phdthesis{Kawohl2022,
  author    = {Kawohl, Alexander},
  title     = {The Petrology and Geochemistry of Igneous Dykes above the Temagami Anomaly (Ontario, Canada) and their Relationship to the 1.85 Ga Sudbury Impact},
  doi       = {10.25972/OPUS-27961},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-279617},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The area northeast of Sudbury, Ontario, is known for one of the largest unexplained geophysical anomalies on the Canadian Shield, the 1,200 km2 Temagami Anomaly. The geological cause of this regional magnetic, conductive and gravity feature has previously been modelled to be a mafic-ultramafic body at relatively great depth (2-15 km) of unknown age and origin, which may or may not be related to the meteorite impact-generated Sudbury Igneous Complex in its immediate vicinity. However, with a profound lack of outcrops and drill holes, the geological cause of the anomaly remains elusive, a genetic link to the 1.85 Ga Sudbury impact event purely speculative. In search for any potential surface expression of the deep-seated cause of the Temagami Anomaly, this study provides a first, yet comprehensive petrological and geochemical assessment of exotic igneous dykes recently discovered in outcrops above, and drill cores into, the Temagami Anomaly. Based on cross-cutting field relations, petrographic studies, lithogeochemistry, whole-rock Nd-Sr-Pb isotope systematics, and U-Pb geochronology, it was possible to identify, and distinguish between, at least six different groups of igneous dykes: (i) Calc-alkaline quartz diorite dykes related to the 1.85 Ga Sudbury Igneous Complex (locally termed Offset Dykes); (ii) tholeiitic quartz diabase of the regional 2.22 Ga Nipissing Suite/Senneterre Dyke Swarm; (iii) calc-alkaline quartz diabase of the regional 2.17 Ga Biscotasing Dyke Swarm; (iv) alkaline ultrabasic dykes correlated with the 1.88-1.86 Ga Circum-Superior Large Igneous Province (LIP); and (v) aplitic dykes as well as (vi) a hornblende syenite, the latter two of more ambiguous age and stratigraphic position. The findings presented in this study - the discovery of three new Offset Dykes in particular - offer some unexpected insights into the geology and economic potential of one of the least explored areas of the world-class Sudbury Mining Camp as well as into the nature and distribution of both allochthonous and autochthonous impactites within one of the oldest and largest impact structures known on Earth. Not only do the geometric patterns of dyke (and breccia) distribution reaffirm previous notions of the existence of discrete ring structures in the sense of a ~200-km multi-ring basin, but they provide critical constraints as to the pre-erosional thickness and extent of the impact melt sheet, thus helping to identity new areas for Ni-Cu-PGE exploration. Furthermore, this study provides important insights into the pre-impact stratigraphy and the magmatic evolution of the region in general, which reveals to be much more complex, compositionally divers, and protracted than initially assumed. Of note is the discovery of rocks related to the 2.17 Ga Biscotasing and the 1.88-1.86 Ga Circum-Superior magmatic events, as these were not previously known to occur on the southeast margin of the Superior Craton. Shortly predating the Sudbury impact and being contemporaneous with ore-forming events at Thompson (Manitoba) and Raglan (Cape Smith), these magmatic rocks could provide the missing link between unusual mafic, pre-enriched, crustal target rocks, and the unique metal endowment of the Sudbury Impact Structure. The actual geological cause of the Temagami Anomaly remains open to debate and requires the downward extension of existing bore holes as well as more detailed geophysical investigations. The hypothesis of a genetic relationship between Sudbury impact event and Temagami Anomaly is neither borne out by any evidence nor particularly realistic, even in case of an oblique impact, and should thus be abandoned. It is instead proposed, based on circumstantial evidence, that the anomaly might be explained by an ultramafic complex of the 1.88-1.86 Ga Circum-Superior LIP.},
  subject      = {Impaktstruktur},
  language  = {en}
}
@phdthesis{Mueller2022,
  author    = {M{\"u}ller, Stefan},
  title     = {Coherent Multiple-Quantum Multidimensional Fluorescence Spectroscopy},
  doi       = {10.25972/OPUS-24411},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244113},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {This thesis describes novel concepts for the measurement of the static and dynamic properties of the electronic structure of molecules and nanocrystals in the liquid phase by means of coherent fluorescence-detected spectroscopy in two and three frequency dimensions. These concepts are based on the systematic variation ("phase cycling") of a sequence of multiple time-delayed femtosecond excitation pulses in order to decode a multitude of novel nonlinear signals from the resulting phase-dependent fluorescence signal. These signals represent any permutation of correlations between zero-, one-, two-, and three-quantum coherences. To this end, two new phase-cycling schemes have been developed which can simultaneously resolve and discriminate several nonlinear signals of sixth order, including those of the fourth order of nonlinearity. By means of the sixth-order signals recorded in this work, static properties of highly excited electronic states in molecules such as their energies, transition dipole moments, and relative displacement of electronic potential surfaces, as well as dynamic properties in terms of their relaxation kinetics, can be ascertained. Furthermore, it was shown that these signals are suitable for the characterization of exciton-exciton correlations in colloidal quantum dots and for the measurement of ultrafast exciton-exciton annihilation in molecular aggregates. The experiments performed in this thesis mark an important step towards the complete characterization of the nonlinear response of quantum systems. In view of this, the concept of fluorescence-detected multiple-quantum coherence multidimensional spectroscopy introduced here offers a unified, systematic approach. In virtue of the technical advantages such as the use of a single excitation beam and the absence of nonresonant contributions, the measurement protocols developed here can be directly transferred to other incoherent observables and to sample systems in other states of matter. Furthermore, the approaches presented here can be systematically extended to higher frequency dimensions and higher orders of nonlinearity.},
  subject      = {Coherent Multidimensional Spectroscopy},
  language  = {en}
}
@phdthesis{Kuehn2022,
  author    = {Kuehn, Laura},
  title     = {Earth-Abundant Metal-Catalyzed and Transition Metal-Free Borylation of Aryl Halides},
  doi       = {10.25972/OPUS-21149},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211499},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The present work focusses on the borylation of aryl halides. The first chapter presents a detailed review about previously reported nickel-catalyzed borylation reactions. The second chapter of the thesis describes, the borylation reaction of C-Cl bonds in aryl chlorides mediated by an NHC-stabilized nickel catalyst. The cyclohexyl substituted NHC Cy2Im was used to synthesize novel Cy2Im-stabilized nickel complexes [Ni2(Cy2Im)4(μ-(η2:η2)-COD)] 1, [Ni(Cy2Im)2(η2-C2H4)] 2, and [Ni(Cy2Im)2(η2-COE)] 3. An optimized procedure was developed using 5 mol\% of the Ni-catalyst, 1.5 equivalents of the boron reagent B2pin2, and 1.5 equivalents of NaOAc as the base in methylcyclohexane at 100 °C. With these optimized conditions, it was shown that a variety of aryl chlorides, containing either electron-withdrawing or -donating groups, were converted to the corresponding aryl boronic esters in yields up to 99\% (88\% isolated) yield. Mechanistic investigations revealed that the C-Cl oxidative addition product [Ni(Cy2Im)2(Cl)(4-F3C-C6H4)] 11, which has been synthesized and isolated separately, also catalyzes the reaction. Thus, rapid oxidative addition of the C-Cl bond of the aryl chloride to [Ni2(Cy2Im)4(μ-(η2:η2)-COD)] 1 to yield trans-[Ni(Cy2Im)2(Cl)(Ar)] represents the first step in the catalytic cycle. The rate limiting step in this catalytic cycle is the transmetalation of boron to nickel forming trans-[Ni(Cy2Im)2(Bpin)(Ar)], which was not possible to isolate. The boryl transfer reagent is assumed to be the anionic adduct Na[B2pin2(OAc)]. A final reductive elimination step gives the desired borylated product Ar-Bpin and regenerates [Ni(Cy2Im)2]. In the next chapter the first effective C-Cl bond borylation of aryl chlorides using NHC-stabilized Cu(I)-complexes of the type [Cu(NHC)(Cl)] was developed. The known complexes [Cu(iPr2Im)(Cl)] 15, [Cu(Me2ImMe)(Cl)] 16, and [Cu(Cy2Im)(Cl)] 17, bearing the small alkyl substituted NHCs, were synthesized in good yields by the reaction of copper(I) chloride with the corresponding free NHC at low temperature (-78 °C) in THF. A range of catalysts, bases, solvents, and boron sources were screened to determine the scope and limitations of this reaction. [Cu(Cy2Im)(Cl)] 17 revealed a significantly higher catalytic activity than [Cu(iPr2Im)(Cl)] 15. KOtBu turned out to be the only efficient base for this borylation reaction. Besides methylcyclohexane, toluene was the only solvent that gave the borylated product in moderate yields of 53\%. It was shown that a variety of electron-rich and electron-poor aryl chlorides can be converted to the corresponding aryl boronic esters in isolated yields of up to 80\%. A mechanism was proposed, in which a Cu-boryl complex [Cu(L)(Bpin)] is formed in the initial step. This is followed by C-B bond formation via σ-bond metathesis with the aryl chloride forming the aryl boronic ester and [Cu(L)(Cl)]. The latter reacts with KOtBu to give [Cu(L)(OtBu)], which regenerates the copper boryl complex by reaction with B2pin2. Chapter 4 describes studies directed towards the transition metal-free borylation of aryl halides using Lewis base adducts of diborane(4) compounds. A variety of novel pyridine and NHC adducts of boron compounds were synthesized. Adducts of the type pyridine·B2cat2 18-19 and NHC·B2(OR)4 20-23 were examined for their ability to transfer a boryl moiety to an aryl iodide. However, only Me2ImMe∙B2pin2 20 was found to be effective. The stoichiometric reaction of 20 with different substituted aryl iodides and bromides in benzene, at elevated temperatures, gave the desired aryl boronic esters in good yields. Interestingly, depending on the reaction temperature, C-C coupling between the aryl halide and the solvent (benzene), was detected leading to a side product which, together with observed hydrodehalogenation of the aryl halide, provided indications that the reaction might be radical in nature. When the boryl transfer reaction based on Me2ImMe∙B2pin2 20 was followed by EPR spectroscopy, a signal (though very weak and ill-defined) was detected, which is suggestive of a mechanism involving a boron-based radical. In addition, the boronium cation [(Me2ImMe)2∙Bpin]+ 37 with iodide as the counterion was isolated from the reaction residue, indicating the fate of the second boryl moiety. A preliminary mechanism for the boryl transfer from 20 to aryl iodides was proposed, which involves an NHC-Bpin˙ radical as the key intermediate. Me2ImMe-Bpin˙ is formed by homolytic B-B bond cleavage of the bis-NHC adduct (Me2ImMe)2∙B2pin2, which is formed in situ in small amounts under the reaction conditions. Me2ImMe-Bpin˙ reacts with the aryl iodide to give the aryl boronic ester with recovery of aromaticity. In the same step, from the second equivalent of NHC-Bpin˙, an NHC-stabilized iodo-Bpin adduct is formed as an intermediate, which is further coordinated by another NHC, yielding [(Me2ImMe)2∙Bpin]+I- 37.},
  subject      = {NHC-Nickel-Catalyst},
  language  = {en}
}
@phdthesis{Hu2022,
  author    = {Hu, Chen},
  title     = {Novel hybrid hydrogels based on poly(2-oxazoline)},
  doi       = {10.25972/OPUS-27935},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-279354},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Motivated by the great potential offered by the combination of additive manufacturing technology and hydrogels, especially in the field of tissue engineering and regenerative medicine, a series of novel hybrid hydrogel inks were developed based on the recently described thermogelling poly(2-oxazoline)s-block-poly(2-oxazine)s diblock copolymers, which may help to expand the platform of available hydrogel inks for this transformative 3D printing technology (Fig. 5.1). In the present thesis, the first reported thermogelling polymer solely consisting of POx and POzi, i.e., the diblock copolymer PMeOx-b-PnPrOzi comprising a hydrophilic block (PMeOx) and a thermoresponsive block (PnPrOzi), was selected and used as a proof-of-concept for the preparation of three novel hybrid hydrogels. Therefore, three batches of the diblock copolymers with a DP of 100 were synthesized for the study of three different hybrid hydrogels with a special focus on their suitability as (bio)inks for extrusion-based 3D printing. The PMeOx-b-PnPrOzi diblock copolymer solution shows a temperature induced reversible gelation behavior above a critical polymer concentration of 20 wt\%, as described for the Pluronic F127 solution but with a unique gelation mechanism, working through the formation of a bicontinuous sponge-like structure from the physically crosslinked vesicles. Specially, its intrinsic shear thinning behavior and excellent recovery property with a certain yield point make it a promising ink candidate for extrusion-based printing technology. Increasing the polymer concentration is the most traditional approach to improve the printability of an ink material, and serve as the major strategy available to improve the printability of PMeOx-b-PnPrOzi systems prior to this work. From the analysis of rheological properties related to printability, it came a conclusion that increasing the copolymer concentration does improve the hydrogel strength and thus the printability. However, such improvement is very limited and usually leads to other problems such as more viscous systems and stringent requirements on the printers, which are not ideal for the printing process and applications especially in the cell-embedded biofabrication field. POx-b-POzi/clay Hybrid Hydrogel An alternative method proposed to improve the printability of this thermoresponsive hydrogel ink is through nanoclay (Laponite XLG) addition, i.e., the first hybrid hydrogel system of PMeOx-b-PnPrOzi/clay (also named shortly as POx-b-POzi/clay) in this thesis. To optimize the viscoelastic properties of the ink material, Laponite XLG acted as a reinforcement additive and a physically crosslinker was blended with the copolymers. Compared with the pristine copolymer solution of PMeOx-b-PnPrOzi, the hybrid PMeOx-b-PnPrOzi/clay solution well retained the temperature induced gelation performance of the copolymers. The obtained hybrid hydrogels exhibited a rapid in situ reversible thermogelation at a physiological relevant Tgel of around 15 ℃ and a rapid recovery of viscoelastic properties within a few seconds. More importantly, with the addition of only a small amount of 1.2 wt\% clay, it exhibited obviously enhanced shear thinning character (n = 0.02), yield stress (240 Pa) and mechanical strength (storage modulus over 5 kPa). With this novel hybrid hydrogel, real three-dimensional constructs with multiple layers and various geometries are generation with greatly enhanced shape fidelity and resolution. In this context, the thermogelling properties of the hybrid hydrogels over a copolymer concentration range of 10-20 wt\% and a clay concentration of 0-4 wt\% were systematically investigated, and from which a printable window was obtained from the laboratory as a reference. In fact, the printing performance of an ink is not only determined by the intrinsic physicochemical properties of the material, but is also influenced by the external printing environments as well as the printer parameter settings. All the printing experiments in this study were conducted under a relatively optimized conditions obtained from preliminary experiments. In future work, the relationship between material rheology properties, printer parameters and printing performance could be systematically explored. Such a fundamental study will help to develop models that allows the prediction and comparison of printing results from different researches based on the parameters available through rheology, which is very beneficial for further development of more advanced ink systems. Although the printability has been significantly improved by the addition of nanoclay Laponite XLG, the hybrid hydrogels and their printed constructs still suffer from some major limitations. For example, these materials are still thermoresponsive, which will cause the printed constructs to collapse when the environment temperature changes below their Tgel. In addition, the formed hydrogel constructs are mechanical too weak for load-bearing applications, and the allowed incubation time is very limited during media exchange/addition as it will lead to dissolution of the hydrogels due to dilution effects. Therefore, it is essential to establish a second (chemical or physical) crosslinking mechanism that allows further solidification of the gels after printing. It should be kept in mind that the second crosslinking step will eliminate the thermoresponsive behavior of the gels and thus the possibility of cell recovery. In this case, besides through the traditional approach of copolymer modification to realize further crosslinking, like one of the well-known post-polymerization modification approach Diels-Alder reaction,[430] designing of interpenetrating networks (IPN) hydrogels serves as one of the major strategy for advanced (bio)ink preparation.[311] Therefore, the second hybrid hydrogel system of PMeOx-b-PnPrOzi/PDMAA/clay (also named shortly as POx-b-POzi/PDMAA/clay) was developed in this thesis, which is a 3D printable and highly stretchable ternary organic-inorganic IPN hydrogel. POx-b-POzi/PDMAA/clay Hybrid Hydrogel The nanocomposite IPN hydrogel combines a thermoresponsive hydrogel with clay described above and in situ polymerized poly(N, N-dimethylacrylamide). Before in situ polymerization, the thermoresponsive hydrogel precursors exhibited thermogelling behavior (Tgel ~ 25 ℃, G' ~ 6 kPa) and shear thinning properties, making the system well-suited for extrusion-based 3D printing. After chemical curing of the 3D-printed constructs by free radical polymerization, the resulting IPN hydrogels show excellent mechanical strength with a high stretchability to a tensile strain at break exceeding 550\%. The hybrid hydrogel can sustain a high stretching deformation and recover quickly due to the energy dissipation from the non-covalent interactions. With this hybrid hydrogel, integrating with the advanced 3D-printing technique, various 3D constructs can be printed and cured successfully with high shape fidelity and geometric accuracy. In this context, we also investigated the possibility of acrylic acid (AA) and 2-hydroxyethylmethacrylate (HEMA) as alternative hydrogel precursors. However, the addition of these two monomers affected the thermogelation of POx-b-POzi in an unfavorable manner, as these monomers competed more effectively with water molecules, preventing the hydration of nPrOzi block at lower temperatures and therefore, the liquefaction of the gels. Furthermore, the influence of the printing process and direction on the mechanical properties of the hydrogel was investigated and compared with the corresponding bulk materials obtained from a mold. No significant effects from the additive manufacturing process were observed due to a homogeneously adhesion and merging between sequentially deposited layers. In the future, further studies on the specific performance differences among hydrogels fabricated at different printing directions/speeds would be of great interest to the community, as this allows for a more accurately control and better predict of the printed structures. This newly developed hybrid IPN hydrogel is expected to expand the material toolbox available for hydrogel-based 3D printing, and may be interesting for a wide range of applications including tissue engineering, drug delivery, soft robotics, and additive manufacturing in general. However, in this case, the low toxicity from the monomer DMAA and other small molecules residuals in the polymerized hydrogels made this hybrid hydrogel not ideal for bioprinting in the field of biofabrication. For this problem, cyto-/biocompatible monomers such as polyethylene glycol diacrylate (PEGDA) can be used as an alternative, while the overall properties of the hydrogels including mechanical properties should be re-evaluated accordingly. Moreover, the swelling behavior of the hydrogels should also be taken into account, as it may most likely affect the mechanical strength and geometry size of the printed scaffold, but is often be overlooked after printing. For example, regarding the specific hybrid hydrogel POx-b-POzi/PDMAA/clay in this work, an equilibrium swelling ratio of 1100\% was determined. The printed hydrogel cuboid experienced a volume increasing over 6-fold after equilibrium swelling in water, and became mechanical fragile due to the formation of a swollen hydrogel network absorbing large amount of water. POx-b-POzi/Alg/clay Hybrid Hydrogel In the final part of this dissertation, to enable the cell-loaded bioprinting and long-term cell culture, the third hybrid hydrogel system POx-b-POzi/Alg/clay was introduced by replacing the monomer DMAA to the natural polysaccharides alginate. Initially, detailed rheological characterization and mechanical tests were performed to evaluate their printability and mechanically properties. Subsequently, some simple patterns were printed with the optimized hydrogel precursor solutions for the preliminary filament fusion and collapse test before proceeding to more complex printings. The fibers showed a sufficient stability which allows the creation of large structures with a height of a few centimeters and a suspended filament up to centimeter. Accordingly, various 3D constructs including suspended filaments were printed successfully with high stackability and shape fidelity. The structure after extrusion was physical crosslinked easily by soaking in CaCl2 solution and, thereafter exhibited a good mechanical flexibility and long-term stability. Interestingly, the mechanical strength and geometry size of the generated scaffolds were well maintained over a culture period of weeks in water, which is of great importance for clinical applications. In addition, the post-printing ionic crosslinking of alginate could also be realized by other di/trivalent cations such as Fe3+ and Tb3+. Subsequently, the cell-laden printing with this hybrid hydrogel and post-printing crosslinking by Ca2+ ions highlighting its feasibility for 3D bioprinting. WST-1 assay of fibroblast suggested no-dose dependent cytocompatibility of the hydrogel precursor solution. The cell distribution was uniform throughout the printed construct, and proliferated with high cell viability during the 21 days culture. The presented hybrid approach, utilizing the beneficial properties of the POx-b-POzi base material, could be interesting for a wide range of bioprinting applications and potentially enabling also other biological bioinks such as collagen, hyaluronic acid, decellularized extracellular matrix or cellulose based bioinks. Although the results look promising and the developed hydrogel is an important bioink candidate, the long-term in vitro cell studies with different cell lines and clinical model establishment are still under investigation, which remains a long road but is of great importance before realizing real clinical application. Last but not least, the improvement to the printability of thermogelling POx/POzi-based copolymers by the clay Laponite XLG was also demonstrated in another thermogelling copolymer PEtOx-b-PnPrOzi. This suggests that the addition of clay may be a general strategy to improve the printability of such polymers. Despite these advances in this work which significantly extended the (bio)material platform of additive manufacturing technology, the competition is still fierce and more work should be done in the further to reveal the potential and limitations of this kind of new and promising candidate (bio)ink materials. It is also highly expected for further creative works based on the thermogelling POx/POzi polymers, such as crosslinking in Ca2+ solution containing monomer acrylamide to prepare printable and mechanically tough hydrogels, research on POx-based support bath material, and print of clinically more relevant sophisticated structures such as 3D microvascular networks omnidirectionally.},
  subject      = {Funktionsgel},
  language  = {en}
}
@phdthesis{CalderonGiraldo2022,
  author    = {Calder{\´o}n Giraldo, Jeniffer},
  title     = {Analysis of estrogen profiles including methoxyestrogen glucuronides: method validation and applicability to human plasma and breast tissue},
  doi       = {10.25972/OPUS-20939},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-209396},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Estrogens, namely 17β-estradiol (E2) and estrone (E1) are considered to play an important role in the initiation and promotion of breast cancer (summarized in Raftogianis et al., 2000), a malignancy responsible for around 500,000 deaths per year (summarized in Ghislain et al., 2016). Two major mechanisms have been postulated to explain the carcinogenic effects of estrogens: (1) the estrogen receptor-mediated stimulation of breast cell proliferation with a concomitant enhanced rate of mutations and (2) the metabolism of hydroxylated estrogens to quinone derivatives which can react with the DNA (Russo and Russo, 2006, summarized in Yager and Davidson, 2006). Nevertheless, as a detoxifying mechanism, E1, E2, and their hydroxylated and methoxylated metabolites are reversibly conjugated into sulfates and glucuronides devoid of biological activity (summarized in Guillemette et al., 2004). Yet, despite the key detoxifying function of these conjugates, the study of their circulating levels face some significant problems: (1) analysis by techniques such as radioimmunoassay lack specificity and accuracy and requires enzymatic/chemical hydrolysis before analysis, being unable to differentiate between sulfates and glucuronides (summarized in Stanczyk et al., 2007, summarized in Wang et al., 2016), (2) very little knowledge in healthy women, which has been identified as a barrier to advance in breast cancer research (summarized in Liu, 2000), and (3) far fewer studies in pre- than in postmenopausal women (summarized in Samavat and Kurzer, 2015). Therefore, to get more insights into the research of breast cancer etiology and prevention, the analysis of circulating levels of estrogens (including metabolites and conjugates) in women without breast cancer through reliable analytical techniques, is required.},
  language  = {en}
}
@phdthesis{Smolan2022,
  author    = {Smolan, Willi},
  title     = {Linear Multifunctional PEG-Alternatives for Bioconjugation and Hydrogel Formation},
  doi       = {10.25972/OPUS-27873},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278734},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The objective of this thesis was the synthesis and characterisation of two linear multifunctional PEG-alternatives for bioconjugation and hydrogel formation: i) Hydrophilic acrylate based copolymers containing peptide binding units and ii) hydrophilic polyether based copolymers containing different functional groups for a physical crosslinking. In section 3.1 the successful synthesis of water soluble and linear acrylate based polymers containing oligo(ethylene glycol) methyl ether acrylate with either linear thioester functional 2-hydroxyethyl acrylate, thiolactone acrylamide, or vinyl azlactone via the living radical polymerisation technique Reversible Addition Fragmentation Chain Transfer (RAFT) and via free-radical polymerisation is described. The obtained polymers were characterized via GPC, 1H NMR, IR and RAMAN spectroscopy. The RAFT end group was found to be difficult to remove from these short polymer chains and accordingly underwent the undesired side reaction aminolysis with the peptide during the conjugation studies. Besides that, polymers without RAFT end groups did not show any binding of the peptide at the thioester groups, which can be improved in future by using higher reactant concentrations and higher amount of binding units at the polymer. Polymers containing the highly reactive azlactone group showed a peptide binding of 19 \%, but unfortunately this function also underwent spontaneous hydrolysis before the peptide could even be bound. In all cases, oligo(ethylene glycol) methyl ether acrylate was used with a relatively high molecular weight (Mn = 480 Da) was used, which eventually was efficiently shielding the introduced binding units from the added peptide. In future, a shorter monomer with Mn = 300 Da or less or hydrophilic N,N'-dialkyl acrylamide based polymers with less steric hindrance could be used to improve this bioconjugation system. Additionally, the amount of monomers containing peptide binding units in the polymer can be increased and have an additional spacer to achieve higher loading efficiency. The water soluble, linear and short polyether based polymers, so called polyglycidols, were successfully synthesized and modified as described in section 3.2. The obtained polymers were characterized using GPC, 1H NMR, 31P{1H} NMR, IR, and RAMAN spectroscopy. The allyl groups which were present up to 20 \% were used for radical induced thiol-ene chemistry for the introduction of functional groups intended for the formation of the physically crosslinking hydrogels. For the positively charged polymers, first a chloride group had to be introduced for the subsequent nucleophilic substitution with the imidazolium compound. There, degrees of modifications were found in the range 40-97 \% due to the repulsion forces of the charges, decreased concentration of active chloride groups, and limiting solution concentrations of the polymer for this reaction. For the negatively charged polymers, first a protected phosphonamide moiety was introduced with a deprotection step afterwards showing 100 \% conversion for all reactions. Preliminary hydrogel tests did not show a formation of a three-dimensional network of the polymer chains which was attributed to the short backbone length of the used polymers, but the gained knowledge about the synthetic routes for the modification of the polymer was successfully transferred to longer linear polyglycidols. The same applies to the introduction of electron rich and electron poor compounds showing π-π stacking interactions by UV-vis spectroscopy. Finally, long linear polyglycidyl ethers were synthesised successfully up to molecular weights of Mn ~ 30 kDa in section 3.3, which was also proven by GPC, 1H NMR, IR and RAMAN spectroscopy. This applies to the homopolymerisation of ethoxyethyl glycidyl ether, allyl glycidyl ether and their copolymerisation with an amount of the allyl compound ~ 10 \%. Attempts for higher molecular weights up to 100 kDa showed an uncontrolled polymerisation behaviour and eventually can be improved in future by choosing a lower initiation temperature. Also, the allyl side groups were modified via radical induced thiol-ene chemistry to obtain positively charged functionalities via imidazolium moieties (85 \%) and negatively charged functionalities via phosphonamide moieties (100 \%) with quantitative degree of modifications. Hydrogel tests have still shown a remaining solution by using long linear polyglycidols carrying negative charges with long/short linear polyglycidols carrying positive charges. The addition of calcium chloride led to a precipitate of the polymer instead of a three-dimensional network formation representing a too high concentration of ions and therefore shielding water molecules with prevention from dissolving the polymer. These systems can be improved by tuning the polymers structure like longer polymer chains, longer spacer between polymer backbone and charge, and higher amount of functional groups. The objective of the thesis was partly reached containing detailed investigated synthetic routes for the design and characterisation of functional polymers which could be used in future with improvements for bioconjugation and hydrogel formation tests.},
  subject      = {Wasserl{\"o}sliche Polymere},
  language  = {en}
}
@phdthesis{Lehenberger2022,
  author    = {Lehenberger, Maximilian},
  title     = {Ecology and Evolution of symbiotic microbial communities in fungus farming ambrosia beetles},
  publisher = {Fungal Ecology, Frontiers in Microbiology, Deutsche Gesellschaft f{\"u}r allgemeine und angewandte Entomologie},
  doi       = {10.25972/OPUS-24154},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241546},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Within my PhD project I gained several novel insights into the poorly investigated symbiotic world of fungus farming ambrosia beetles and their bark beetle ancestors, where I especially focused on physiological interactions and capabilities of associated fungal symbionts. Here, (i) I could confirm the association of mutualistic Phialophoropsis fungi with the ambrosia beetle genus Trypodendron and found hints for a possible new Phialophoropsis species in T. signatum and T. domesticum. Moreover, I could show that mutualistic fungi of Trypodendron ambrosia beetles are able to decompose major woody polysaccharides such as cellulose and xylan. Additionally, (ii) I provided the first images using micro-computed tomography (µCT) of the formerly unknown structure of the mycetangium of Trypodendron leave. (iii) I could confirm a general tolerance towards ethanol in mutualistic ambrosia beetle fungi, while antagonistic fungi as well as most examined fungal bark beetle associates (e.g. possibly tree-defense detoxifying species) were highly sensitive to even low concentrations of ethanol. Further, (iv) I found that natural galleries of ambrosia beetles are highly enriched with several biologically important elements (such as N, P, S, K, Mg) compared to the surrounding woody tissue and suggest that mutualistic fungi are translocating and concentrating elements from the immediate surrounding xylem to the beetles galleries. Furthermore, (v) I could show that various fungi associated with bark and ambrosia beetles (mutualists, possibly beneficial symbionts) are emitting several volatile organic compounds mostly within aliphatic and aromatic alcohols and esters, while non-mutualistic and free living species were generally emitting a lower number and amount of volatiles. Finally, especially bark and ambrosia beetle fungi were found to incorporate several amino acids, from which some are especially important for the production of certain volatile organic compounds. Amino acid content also indicated a higher nutritional value for certain species. Here, I propose that especially volatile organic compounds are widespread key players in maintaining various symbioses between fungi and beetles, as already proven by a recent study on the bark beetle Ips typographus (as well as for some other bark beetle-fungus symbioses, see summary in Kandasamy et al. 2016) and also suggested for ambrosia beetles.},
  language  = {en}
}
@phdthesis{Schamberger2022,
  author    = {Schamberger, Tamara Svenja},
  title     = {Methodological Advances in Composite-based Structural Equation Modeling},
  isbn      = {978-90-365-5375-9},
  doi       = {10.3990/1.9789036553759},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276794},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {This thesis is about composite-based structural equation modeling. Structural equation modeling in general can be used to model both theoretical concepts and their relations to one another. In traditional factor-based structural equation modeling, these theoretical concepts are modeled as common factors, i.e., as latent variables which explain the covariance structure of their observed variables. In contrast, in composite-based structural equation modeling, the theoretical concepts can be modeled both as common factors and as composites, i.e., as linear combinations of observed variables that convey all the information between their observed variables and all other variables in the model. This thesis presents some methodological advancements in the field of composite-based structural equation modeling. In all, this thesis is made up of seven chapters. Chapter 1 provides an overview of the underlying model, as well as explicating the meaning of the term composite-based structural equation modeling. Chapter 2 gives guidelines on how to perform Monte Carlo simulations in the statistic software R using the package "cSEM" with various estimators in the context of composite-based structural equation modeling. These guidelines are illustrated by an example simulation study that investigates the finite sample behavior of partial least squares path modeling (PLS-PM) and consistent partial least squares (PLSc) estimates, particularly regarding the consequences of sample correlations between measurement errors on statistical inference. The third Chapter presents estimators of composite-based structural equation modeling that are robust in responding to outlier distortion. For this purpose, estimators of composite-based structural equation modeling, PLS-PM and PLSc, are adapted. Unlike the original estimators, these adjustments can avoid distortion that could arise from random outliers in samples, as is demonstrated through a simulation study. Chapter 4 presents an approach to performing predictions based on models estimated with ordinal partial least squares and ordinal consistent partial least squares. Here, the observed variables lie on an ordinal categorical scale which is explicitly taken into account in both estimation and prediction. The prediction performance is evaluated by means of a simulation study. In addition, the chapter gives guidelines on how to perform such predictions using the R package "cSEM". This is demonstrated by means of an empirical example. Chapter 5 introduces confirmatory composite analysis (CCA) for research in "Human Development". Using CCA, composite models can be estimated and assessed. This chapter uses the Henseler-Ogasawara specification for composite models, allowing, for example, the maximum likelihood method to be used for parameter estimation. Since the maximum likelihood estimator based on the Henseler-Ogasawara specification has limitations, Chapter 6 presents another specification of the composite model by means of which composite models can be estimated with the maximum likelihood method. The results of this maximum likelihood estimator are compared with those of PLS-PM, thus showing that this maximum likelihood estimator gives valid results even in finite samples. The last chapter, Chapter 7, gives an overview of the development and different strands of composite-based structural equation modeling. Additionally, here I examine the contribution the previous chapters make to the wider distribution of composite-based structural equation modeling.},
  subject      = {Structural Equation Modeling},
  language  = {en}
}
@phdthesis{Duque2022,
  author    = {Duque, Laura Maria Ribeiro},
  title     = {Effects of ozone on plants and plant-insect interactions},
  doi       = {10.25972/OPUS-27798},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277983},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Anthropogenic activities are causing air pollution. Amongst air pollutants, tropospheric ozone is a major threat to human health and ecosystem functioning. In this dissertation, I present three studies that aimed at increasing our knowledge on how plant exposure to ozone affects its reproduction and its interactions with insect herbivores and pollinators. For this purpose, a new fumigation system was built and placed in a greenhouse. The annual plant Sinapis arvensis (wild mustard) was used as the model plant. Plants were exposed to either 0 ppb (control) or 120 ppb of ozone, for variable amounts of time and at different points of their life cycle. After fumigation, plants were exposed to herbivores or pollinators in the greenhouse, or to both groups of insects in the field. My research shows that ozone affected reproductive performance differently, depending on the timing of exposure: plants exposed at earlier ages had their reproductive fitness increased, while plants exposed later in their life cycle showed a tendency for reduced reproductive fitness. Plant phenology was a key factor influencing reproductive fitness: ozone accelerated flowering and increased the number of flowers produced by plants exposed at early ages, while plants exposed to ozone at later ages tended to have fewer flowers. On the other hand, the ozone-mediated changes in plant-insect interactions had little impact on plant reproductive success. The strongest effect of ozone on plant-pollinator interactions was the change in the number of flower visits received per plant, which was strongly linked to the number of open flowers. This means that, as a rule, exposure of plants to ozone early in the life cycle resulted in a higher number of pollinator visits, while exposure later in the life cycle resulted in fewer flower visits by potential pollinators. An exception was observed: the higher number of visits performed by large syrphid flies to young ozone-exposed plants than to the respective control plants went beyond the increase in the number of open flowers in those plants. Also, honeybees spent more time per flower in plants exposed to ozone than on control plants, while other pollinators spent similar amounts of time in control and ozone-exposed plants. This guild-dependent preference for ozone-exposed plants may be due to species-specific preferences related to changes in the quality and quantity of floral rewards. In the field, ozone-exposed plants showed only a tendency for increased colonization by sucking herbivores and slightly more damage by chewing herbivores than control plants. On the other hand, in the greenhouse experiment, Pieris brassicae butterflies preferred control plants over ozone-exposed plants as oviposition sites. Eggs laid on ozone-exposed plants took longer to hatch, but the chances of survival were higher. Caterpillars performed better in control plants than in ozone-exposed plants, particularly when the temperature was high. Most of the described effects were dependent on the duration and timing of the ozone exposure and the observed temperature, with the strongest effects being observed for longer exposures and higher temperatures. Furthermore, the timing of exposure altered the direction of the effects. The expected climate change provides ideal conditions for further increases in tropospheric ozone concentrations, therefore for stronger effects on plants and plant-insect interactions. Acceleration of flowering caused by plant exposure to ozone may put plant-pollinator interactions at risk by promoting desynchronization between plant and pollinator activities. Reduced performance of caterpillars feeding on ozone-exposed plants may weaken herbivore populations. On the other hand, the increased plant reproduction that results from exposing young plants to ozone may be a source of good news in the field of horticulture, when similar results would be achieved in high-value crops. However, plant response to ozone is highly species-specific. In fact, Sinapis arvensis is considered a weed and the advantage conferred by ozone exposure may increase its competitiveness, with negative consequences for crops or plant communities in general. Overall, plant exposure to ozone might constitute a threat for the balance of natural and agro-ecosystems.},
  subject      = {Plant},
  language  = {en}
}
@phdthesis{Kortum2022,
  author    = {Kortum, Joshua},
  title     = {Global Existence and Uniqueness Results for Nematic Liquid Crystal and Magnetoviscoelastic Flows},
  doi       = {10.25972/OPUS-27827},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278271},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Liquid crystals and polymeric fluids are found in many technical applications with liquid crystal displays probably being the most prominent one. Ferromagnetic materials are well established in industrial and everyday use, e.g. as magnets in generators, transformers and hard drive disks. Among ferromagnetic materials, we find a subclass which undergoes deformations if an external magnetic field is applied. This effect is exploited in actuators, magnetoelastic sensors, and new fluid materials have been produced which retain their induced magnetization during the flow. A central issue consists of a proper modelling for those materials. Several models exist regarding liquid crystals and liquid crystal flows, but up to now, none of them has provided a full insight into all observed effects. On materials encompassing magnetic, elastic and perhaps even fluid dynamic effects, the mathematical literature seems sparse in terms of models. To some extent, one can unify the modeling of nematic liquid crystals and magnetoviscoelastic materials employing a so-called energetic variational approach. Using the least action principle from theoretical physics, the actual task reduces to finding appropriate energies describing the observed behavior. The procedure leads to systems of evolutionary partial differential equations, which are analyzed in this work. From the mathematical point of view, fundamental questions on existence, uniqueness and stability of solutions remain unsolved. Concerning the Ericksen-Leslie system modelling nematic liquid crystal flows, an approximation to this model is given by the so-called Ginzburg-Landau approximation. Solutions to the latter are intended to approximately represent solutions to the Ericksen-Leslie system. Indeed, we verify this presumption in two spatial dimensions. More precisely, it is shown that weak solutions of the Ginzburg-Landau approximation converge to solutions of the Ericksen-Leslie system in the energy space for all positive times of evolution. In order to do so, theory for the Euler equations invented by DiPerna and Majda on weak compactness and concentration measures is used. The second part of the work deals with a system of partial differential equations modelling magnetoviscoelastic fluids. We provide a well-posedness result in two spatial dimensions for large energies and large times. Along the verification of that conclusion, existing theory on the Ericksen-Leslie system and the harmonic map flow is deployed and suitably extended.},
  subject      = {Magnetoelastizit{\"a}t},
  language  = {en}
}
@phdthesis{Sbiera2022,
  author    = {Sbiera, Iuliu},
  title     = {Possible role of epithelial to mesenchymal transition and its associated FGF/FGFR pathway in adrenocortical carcinoma},
  doi       = {10.25972/OPUS-27745},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277454},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Recent studies have hinted to an involvement of epithelial to mesenchymal transition, a mechanism often associated with metastasis in epithelial cancers, in adrenocortical carcinoma. In addition, the knowledge about the FGF/FGFR pathway in pathogenesis of the adrenal gland, a pathway often associated with the epithelial to mesenchymal transition, is sparse and fragmented. We assessed, in a large number of normal, benign and malignant adrenocortical tissues (a total of 181 different samples), the expression of canonical and novel epithelial and mesenchymal markers and compared it with their expression in typical epithelial and mesenchymal tissues. In addition, we also quantified the expression of most members of the FGF/FGFR pathway in adrenocortical tissues and compared it against well-studied epithelial and mesenchymal tissues as well as between malignant and not malignant adrenocortical tissues, in order to assess the possible connection to epithelial to mesenchymal transition and find possible drug targets. Surprisingly, both normal and neoplastic adrenocortical tissues lacked expression of epithelial markers (e.g. E-Cadhering or EpCAM) but strongly expressed mesenchymal markers (e.g. N-Cadherin or SLUG), suggesting a higher similarity of adrenocortical tissues to mesenchymal compared to epithelial tissues, reminiscent of the adrenocortical origin from the intermediate mesoderm. Despite their ubiquitous expression in all adrenocortical tissues, mesenchymal markers had a variable expression in adrenocortical carcinoma, associating either directly or inversely with different clinical markers of tumor aggressiveness. Lymph node infiltration was associated with high expression of SLUG (p = 0.04), and at the same time low expression of N-cadherin (p = 0.001), and the same pattern was observed for venous infiltration of tumoral tissue, Weiss score of tumor malignancy or Ki67 proliferation marker. In malignant compared to benign adrenal tumors, we found significant differences in the expression of 16 out of the 94 studied FGF receptor pathway related genes. Genes involved in tissue differentiation and metastatic spread through epithelial to mesenchymal transition were most strongly altered. The therapeutically targetable FGF receptors 1 and 4 were upregulated 4.6- and 6-fold, respectively, in malignant compared to benign adrenocortical tumors, which was confirmed by using two different quantification methods in both frozen and paraffin embedded tissue material. High expression of FGFR1 and 4 was significantly associated with worse patient prognosis (High FGFR1 expression was associated with a shorter overall patient survival of 84 vs 148 months (HR=1.8, 95\% CI: 1.01-3.25) as well as a shorter resection free survival of 25 vs 75 months ((HR=2.93, 95\% CI: 1.25-6.84), while high FGFR4 was associated with a much shorter overall survival of 50 vs 155 months (HR=2.44, 95\% CI: 1.41-4.22). In conclusion, epithelial to mesenchymal transition does not seem to play a role in adrenocortical carcinoma tumor progression, and the FGF/FGFR pathway, even if it is probably not related to EMT, is nonetheless associated with tumor aggressiveness. Furthermore, quantification of FGF receptors may enable a stratification of adrenocortical carcinoma for the use of FGFR inhibitors in future clinical trials.},
  subject      = {Nebennierenrindenkrebs},
  language  = {en}
}
@phdthesis{Griebel2022,
  author    = {Griebel, Matthias},
  title     = {Applied Deep Learning: from Data to Deployment},
  doi       = {10.25972/OPUS-27765},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277650},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Novel deep learning (DL) architectures, better data availability, and a significant increase in computing power have enabled scientists to solve problems that were considered unassailable for many years. A case in point is the "protein folding problem", a 50-year-old grand challenge in biology that was recently solved by the DL-system AlphaFold. Other examples comprise the development of large DL-based language models that, for instance, generate newspaper articles that hardly differ from those written by humans. However, developing unbiased, reliable, and accurate DL models for various practical applications remains a major challenge - and many promising DL projects get stuck in the piloting stage, never to be completed. In light of these observations, this thesis investigates the practical challenges encountered throughout the life cycle of DL projects and proposes solutions to develop and deploy rigorous DL models. The first part of the thesis is concerned with prototyping DL solutions in different domains. First, we conceptualize guidelines for applied image recognition and showcase their application in a biomedical research project. Next, we illustrate the bottom-up development of a DL backend for an augmented intelligence system in the manufacturing sector. We then turn to the fashion domain and present an artificial curation system for individual fashion outfit recommendations that leverages DL techniques and unstructured data from social media and fashion blogs. After that, we showcase how DL solutions can assist fashion designers in the creative process. Finally, we present our award-winning DL solution for the segmentation of glomeruli in human kidney tissue images that was developed for the Kaggle data science competition HuBMAP - Hacking the Kidney. The second part continues the development path of the biomedical research project beyond the prototyping stage. Using data from five laboratories, we show that ground truth estimation from multiple human annotators and training of DL model ensembles help to establish objectivity, reliability, and validity in DL-based bioimage analyses. In the third part, we present deepflash2, a DL solution that addresses the typical challenges encountered during training, evaluation, and application of DL models in bioimaging. The tool facilitates the objective and reliable segmentation of ambiguous bioimages through multi-expert annotations and integrated quality assurance. It is embedded in an easy-to-use graphical user interface and offers best-in-class predictive performance for semantic and instance segmentation under economical usage of computational resources.},
  language  = {en}
}
@phdthesis{Schmitt2022,
  author    = {Schmitt, Norbert},
  title     = {Measurement, Modeling, and Emulation of Power Consumption of Distributed Systems},
  doi       = {10.25972/OPUS-27658},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276582},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Today's cloud data centers consume an enormous amount of energy, and energy consumption will rise in the future. An estimate from 2012 found that data centers consume about 30 billion watts of power, resulting in about 263TWh of energy usage per year. The energy consumption will rise to 1929TWh until 2030. This projected rise in energy demand is fueled by a growing number of services deployed in the cloud. 50\% of enterprise workloads have been migrated to the cloud in the last decade so far. Additionally, an increasing number of devices are using the cloud to provide functionalities and enable data centers to grow. Estimates say more than 75 billion IoT devices will be in use by 2025. The growing energy demand also increases the amount of CO2 emissions. Assuming a CO2-intensity of 200g CO2 per kWh will get us close to 227 billion tons of CO2. This emission is more than the emissions of all energy-producing power plants in Germany in 2020. However, data centers consume energy because they respond to service requests that are fulfilled through computing resources. Hence, it is not the users and devices that consume the energy in the data center but the software that controls the hardware. While the hardware is physically consuming energy, it is not always responsible for wasting energy. The software itself plays a vital role in reducing the energy consumption and CO2 emissions of data centers. The scenario of our thesis is, therefore, focused on software development. Nevertheless, we must first show developers that software contributes to energy consumption by providing evidence of its influence. The second step is to provide methods to assess an application's power consumption during different phases of the development process and to allow modern DevOps and agile development methods. We, therefore, need to have an automatic selection of system-level energy-consumption models that can accommodate rapid changes in the source code and application-level models allowing developers to locate power-consuming software parts for constant improvements. Afterward, we need emulation to assess the energy efficiency before the actual deployment.},
  subject      = {Leistungsbedarf},
  language  = {en}
}
@phdthesis{KayisogluKaya2022,
  author    = {Kayisoglu-Kaya, {\"O}zge},
  title     = {Analysis of gastrointestinal epithelial innate immune barrier using human and murine organoids as a model},
  doi       = {10.25972/OPUS-27749},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277497},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The epithelial layer of the gastrointestinal (GI) tract provides a barrier between the environment and the body. Dysfunction of the epithelium, including changes of the innate immune response facilitated by pattern recognition receptors (PRRs), plays a major role in the development of GI disorders. However, the organization of innate immune sensing, the expression and activity of PRRs and the factors contri¬buting to such possible organization along the GI tract are unclear. In recent years, stem cell-derived organoids gained increasing attention as promising tissue models. Here, a biobank of human and murine organoids comprising three lines from each GI segment; corpus, pylorus, duodenum, jejunum, ileum, colon was generated. RNA sequencing of 42 lines confirmed the preservation of tissue identity and revealed an extensive organization of innate immune signaling components along the cephalocaudal axis, giving each segment a specific innate immune profile. Comple-menting the region-specific expression analysis, several PRRs in human and murine organoids showed region- and species-specific function. To investigate the factors contributing to the patterning of innate immunity in the GI tract, the impact of microbial components was analyzed using murine embryo-derived, never colonized gastric and proximal intestinal organoids. Transcriptional profiling of embryo-derived organoids showed that while expression of some PRRs may depend on environmental cues as expected, an unexpectedly large part of segment-specific expression of PRR signaling components is independent of prior contact with microbial products. Further, analysis of published RNA-seq data as well as in vitro experiments using directed differentiation of organoids into specific cell types showed that expression of innate immune gene also depended on cellular differentiation along the crypt-villus axis. This underlined the importance of cellular differentiation rather than contact to microbial compounds for expression of PRRs. Lastly, analysis of published datasets of RNA-seq and ATAC-seq after knockout of the intestinal transcription factor Cdx2 demonstrated that Cdx2 is likely important for the expression of Nlrp6 and Naip1 in the murine intestine. Future experiments have to support these preliminary findings. Taken together, the expression of a large part of epithelial innate immunity is develop¬mentally defined and conserved in tissue-resident stem cells. The identification of mechanisms governing expression of genes related to immunity will provide further insights into the mechanisms that play a role in the progress of inflammatory diseases.},
  subject      = {Organoid},
  language  = {en}
}
@phdthesis{Barth2022,
  author    = {Barth, Dominik},
  title     = {Computation of multi-branch-point covers and applications in Galois theory},
  doi       = {10.25972/OPUS-27702},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277025},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {We present a technique for computing multi-branch-point covers with prescribed ramification and demonstrate the applicability of our method in relatively large degrees by computing several families of polynomials with symplectic and linear Galois groups. As a first application, we present polynomials over \(\mathbb{Q}(\alpha,t)\) for the primitive rank-3 groups \(PSp_4(3)\) and \(PSp_4(3).C_2\) of degree 27 and for the 2-transitive group \(PSp_6(2)\) in its actions on 28 and 36 points, respectively. Moreover, the degree-28 polynomial for \(PSp_6(2)\) admits infinitely many totally real specializations. Next, we present the first (to the best of our knowledge) explicit polynomials for the 2-transitive linear groups \(PSL_4(3)\) and \(PGL_4(3)\) of degree 40, and the imprimitive group \(Aut(PGL_4(3))\) of degree 80. Additionally, we negatively answer a question by K{\"o}nig whether there exists a degree-63 rational function with rational coefficients and monodromy group \(PSL_6(2)\) ramified over at least four points. This is achieved due to the explicit computation of the corresponding hyperelliptic genus-3 Hurwitz curve parameterizing this family, followed by a search for rational points on it. As a byproduct of our calculations we obtain the first explicit \(Aut(PSL_6(2))\)-realizations over \(\mathbb{Q}(t)\). At last, we present a technique by Elkies for bounding the transitivity degree of Galois groups. This provides an alternative way to verify the Galois groups from the previous chapters and also yields a proof that the monodromy group of a degree-276 cover computed by Monien is isomorphic to the sporadic 2-transitive Conway group \(Co_3\).},
  subject      = {Galois-Theorie},
  language  = {en}
}
@phdthesis{Kissner2022,
  author    = {Kißner, Katharina},
  title     = {Manipulation of electronic properties in strongly correlated Cerium-based surface alloys},
  doi       = {10.25972/OPUS-27306},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-273067},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Photoelectron spectroscopy proves as a versatile tool for investigating various aspects of the electronic structure in strongly correlated electron systems. Influencing the manifestation of strong correlation in Ce-based surface alloys is the main task of this work. It is shown, that the manifestation of the Kondo ground state is influenced by a multitude of parameters such as the choice of the metal binding partner in binary Ce compounds, the surface alloy layer thickness and accompanying variations in the lattice structure as well as the interfaces to substrate or vacuum. Gaining access to these parameters allows to directly influence essential state variables, such as the f level occupancy nf or the Kondo temperature TK. The center of this work are the intermetallic thin films of CePt5/Pt(111) and CeAgx/Ag(111). By utilizing different excitation energies, photoemission spectroscopy provides access to characteristic features of Kondo physics in the valence band, such as the Kondo resonance and its spin-orbit partner at the Fermi level, as well as the multiplet structure of the Ce 3d core levels. In this work both approaches are applied to CePt5/Pt(111) to determine nf and TK for a variety of surface alloy layer thicknesses. A temperature dependent study of the Ce 3d core levels allows to determine the systems TK for the different layer thicknesses. This leads to TK ≈200-270K in the thin layer thickness regime and TK >280K for larger layer thicknesses. These results are confirmed by fitting the Ce 3d multiplet based on the Gunnarsson-Sch{\"o}nhammer formalism for core level spectroscopy and additionally by valence band photoemission spectra of the respective Kondo resonances. The influence of varying layer thickness on the manifestation of strong correlation is subsequently studied for the surface alloy CeAgx/Ag(111). Furthermore, the heavy element Bi is added, to investigate the effects of strong spin-orbit coupling on the electronic structure of the surface alloy.},
  subject      = {Korrelation},
  language  = {en}
}
@phdthesis{Seifert2022,
  author    = {Seifert, Annika Kristina},
  title     = {Unidirectional freezing of soft and hard matter for biomedical applications},
  doi       = {10.25972/OPUS-27728},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277281},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {A multitude of human tissues, such as bones, tendons, or muscles, are characterized by a hierarchical and highly ordered structure. In many cases, the loss of these tissues requires reconstruction using biocompatible replacement materials. In the field of bone replacement, the pore structure of the material has a crucial influence. Anisotropic porosity would have the advantage of facilitating the ingrowth of cells and newly formed blood vessels as well as the transport of nutrients. In this thesis, scaffolds with a highly ordered and anisotropic pore structure were fabricated using unidirectional freezing. Systematic investigations were carried out on biopolymer solutions (alginate and chitosan) to gain a deeper understanding of the freeze-structuring process. The knowledge gained was then applied to the development of anisotropically structured bone substitute materials. Here, the previously existing material platform for anisotropically structured calcium phosphates was extended to low-temperature phases such as calcium deficient hydroxyapatite (CDHA) or the secondary phosphates monetite and brushite. After the implantation of a biomaterial, the inevitably triggered initial immune response plays a key role in the success of a graft, with immune cells such as neutrophils or macrophages being of particular importance. In this thesis, the influence of anisotropically structured alpha-TCP and CDHA scaffolds as well as their unstructured references on human monocytes/macrophages was investigated. Macrophages produced extracellular traps (ETs) due to mineral nanoparticles formed by the binding of phosphate and calcium ions to human platelet lysate. In particular, incubation of alpha-TCP samples in lysate containing cell culture medium resulted in pronounced particle formation and enhanced release of ETs.},
  subject      = {Freezing},
  language  = {en}
}
@phdthesis{Schickhardt2022,
  author    = {Schickhardt, Irene},
  title     = {A Process Model for Selecting the Most Appropriate Production Site : an Application-oriented Approach for OEMs based on a Literature Analysis},
  doi       = {10.25972/OPUS-27665},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276652},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The global selection of production sites is a very complex task of great strategic importance for Original Equipment Manufacturers (OEMs), not only to ensure their sustained competitiveness, but also due to the sizeable long-term investment associated with a production site. With this in mind, this work develops a process model with which OEMs can select the most appropriate production site for their specific production activity in practice. Based on a literature analysis, the process model is developed by determining all necessary preparation, by defining the properties of the selection process model, providing all necessary instructions for choosing and evaluating location factors, and by laying out the procedure of the selection process model. Moreover, the selection process model includes a discussion of location factors which are possibly relevant for OEMs when selecting a production site. This discussion contains a description and, if relevant, a macroeconomic analysis of each location factor, an explanation of their relevance for constructing and operating a production site, additional information for choosing relevant location factors, and information and instructions on evaluating them in the selection process model. To be successfully applicable, the selection process model is developed based on the assumption that the production site must not be selected in isolation, but as part of the global production network and supply chain of the OEM and, additionally, to advance the OEM's related strategic goals. Furthermore, the selection process model is developed on the premise that a purely quantitative model cannot realistically solve an OEM's complex selection of a production site, that the realistic analysis of the conditions at potential production sites requires evaluating the changes of these conditions over the planning horizon of the production site and that the future development of many of these conditions can only be assessed with uncertainty.},
  subject      = {Produktionsstandort},
  language  = {en}
}
@phdthesis{Kaiser2022,
  author    = {Kaiser, Dustin},
  title     = {Non-standard computational approaches applied to molecular systems},
  doi       = {10.25972/OPUS-27664},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276641},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In this thesis, several contributions to the understanding and modeling of chemical phenomena using computational approaches are presented. These investigations are characterized by the usage of non-standard computational modeling techniques, which is necessitated by the complex nature of the electronic structure or atomic fluctuations of the target molecules. Multiple biradical-type molecules and their spectroscopic properties were modeled. In the course of the investigation, it is found that especially the impact of correct molecular geometries on the computationally predicted absorption properties may be critical. In order to find the correct minimum geometries, Multi-Reference methods may have to be invoked. The impact of geometry relaxation on the excitonic properties of Perylene Bisimide dimers were investigated. Oftentimes, these geometry factors are neglected in Organic Semiconductor modeling as an approximation. This present investigation suggests that this approximation is not always valid, as certain regimes are identified where geometrical parameters have critical impact on the localization and energetic properties of excitons. The mechanism of the Triazolinedione (TAD) tyrosine bioconjugation reaction is investigated using quantum-chemical methods. By comparison of different conceivable mechanisms and their energetic ordering, the TAD tyrosine bioconjugation is found to proceed by means of a base-mediated electrophilic aromatic substitution reaction. The kth nearest neighbor entropy estimation protocol is investigated. This estimator promises accurate entropy estimates even for flexible molecules with multiple structural minima. Our granular investigation of formal and practical properties of the estimator suggests that the uneven variance of a molecule's vibrational modes is the cause of the observed slow convergence of the estimator. A rescaling procedure to reestablish fast convergence is suggested and benchmarks are performed.},
  subject      = {Quantenchemie},
  language  = {en}
}