@phdthesis{Schampel2017, author = {Schampel, Andrea}, title = {Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis - an animal model for multiple sclerosis}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148952}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Multiple sclerosis (MS) is the most prevalent neurological disease of the central nervous system (CNS) in young adults and is characterized by inflammation, demyelination and axonal pathology that result in multiple neurological and cognitive deficits. The focus of MS research remains on modulating the immune response, but common therapeutic strategies are only effective in slowing down disease progression and attenuating the symptoms; they cannot cure the disease. Developing an option to prevent neurodegeneration early on would be a valuable addition to the current standard of care for MS. Based on our results we suggest that application of nimodipine could be an effective way to target both neuroinflammation and neurodegeneration. We performed detailed analyses of neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and in in vitro experiments regarding the effect of the clinically well-established L-type calcium channel antagonist nimodipine. Nimodipine treatment attenuated the course of EAE and spinal cord histopathology. Furthermore, it promoted remyelination. The latter could be due to the protective effect on oligodendrocytes and oligodendrocyte precursor cells (OPCs) we observed in response to nimodipine treatment. To our surprise, we detected calcium channel-independent effects on microglia, resulting in apoptosis. These effects were cell type-specific and independent of microglia polarization. Apoptosis was accompanied by decreased levels of nitric oxide (NO) and inducible NO synthase (iNOS) in cell culture as well as decreased iNOS expression and reactive oxygen species (ROS) activity in EAE. Overall, application of nimodipine seems to generate a favorable environment for regenerative processes and could therefore be a novel treatment option for MS, combining immunomodulatory effects while promoting neuroregeneration.}, subject = {Nimodipin}, language = {en} } @phdthesis{Horn2017, author = {Horn, Hannes}, title = {Analysis and interpretation of (meta-)genomic data from host-associated microorganisms}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152035}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Host-microbe interactions are the key to understand why and how microbes inhabit specific environments. With the scientific fields of microbial genomics and metagenomics, evolving on an unprecedented scale, one is able to gain insights in these interactions on a molecular and ecological level. The goal of this PhD thesis was to make (meta-)genomic data accessible, integrate it in a comparative manner and to gain comprehensive taxonomic and functional insights into bacterial strains and communities derived from two different environments: the phyllosphere of Arabidopsis thaliana and the mesohyl interior of marine sponges. This thesis focused first on the de novo assembly of bacterial genomes. A 5-step protocol was developed, each step including a quality control. The examination of different assembly software in a comparative way identified SPAdes as most suitable. The protocol enables the user to chose the best tailored assembly. Contamination issues were solved by an initial filtering of the data and methods normally used for the binning of metagenomic datasets. This step is missed in many published assembly pipelines. The described protocol offers assemblies of high quality ready for downstream analysis. Subsequently, assemblies generated with the developed protocol were annotated and explored in terms of their function. In a first study, the genome of a phyllosphere bacterium, Williamsia sp. ARP1, was analyzed, offering many adaptions to the leaf habitat: it can deal with temperature shifts, react to oxygen species, produces mycosporins as protection against UV-light, and is able to uptake photosynthates. Further, its taxonomic position within the Actinomycetales was infered from 16S rRNA and comparative genomics showing the close relation between the genera Williamsia and Gordonia. In a second study, six sponge-derived actinomycete genomes were investigated for secondary metabolism. By use of state-of-the-art software, these strains exhibited numerous gene clusters, mostly linked to polykethide synthases, non-ribosomal peptide synthesis, terpenes, fatty acids and saccharides. Subsequent predictions on these clusters offered a great variety of possible produced compounds with antibiotic, antifungal or anti-cancer activity. These analysis highlight the potential for the synthesis of natural products and the use of genomic data as screening toolkit. In a last study, three sponge-derived and one seawater metagenomes were functionally compared. Different signatures regarding the microbial composition and GC-distribution were observed between the two environments. With a focus on bacerial defense systems, the data indicates a pronounced repertoire of sponge associated bacteria for bacterial defense systems, in particular, Clustered Regularly Interspaced Short Palindromic Repeats, restriction modification system, DNA phosphorothioation and phage growth limitation. In addition, characterizing genes for secondary metabolite cluster differed between sponge and seawater microbiomes. Moreover, a variety of Type I polyketide synthases were only found within the sponge microbiomes. With that, metagenomics are shown to be a useful tool for the screening of secondary metabolite genes. Furthermore, enriched defense systems are highlighted as feature of sponge-associated microbes and marks them as a selective trait.}, subject = {Bakterien}, language = {en} } @misc{Shane2017, type = {Master Thesis}, author = {Shane, Nadine}, title = {The Country-of-Origin Effect and its Potential Impact on How German Consumers Perceive Chinese Luxury Goods}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153047}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {This thesis investigates the impact of the country-of-origin effect on Chinese luxury brands which intend to enter the German luxury goods market. By means of a questionnaire and a quantitative analysis, possible threats to Chinese newcomers that derive from an unfavorable country image are illustrated. In fact, the Chinese origin of luxury goods has an impact on German consumers' perception.}, subject = {China}, language = {en} } @phdthesis{Liess2017, author = {Liess, Andreas}, title = {Structure-Property Relationships of Merocyanine Dyes in the Solid State: Charge Transport and Exciton Coupling}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152900}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {The present thesis demonstrates the importance of the solid state packing of dipolar merocyanine dyes with regard to charge transport and exciton coupling. Due to the charge transport theory for disordered materials, it is expected that high ground state dipole moments in amorphous thin films lead to low mobility values due to a broadening of the density of states. However, due to their inherent dipolarity, merocyanine dyes usually align in antiparallel dimers in an ordered fashion. The examination of twenty different molecules with ground state dipole moments up to 15.0 D shows that by a high dipolarity and well-defined sterics, the molecules pack in a highly regular two-dimensional brickwork-type structure, which is beneficial for hole transport. Utilization of these molecules for organic thin-film transistors (OTFTs) leads to hole mobility values up to 0.21 cm²/Vs. By fabrication of single crystal field-effect transistors (SCFETs) for the derivative showing the highest mobility values in OTFTs, even hole mobilities up to 2.34 cm²/Vs are achieved. Hence, merocyanine based transistors show hole mobility values comparable to those of conventional p-type organic semiconductors and therefore high ground state dipole moments are not necessarily disadvantageous regarding high mobility applications. By examination of a different series of ten merocyanine dyes with the same chromophore backbone but different donor substituents, it is demonstrated that the size of the donor has a significant influence on the optical properties of thin films. For small and rigid donor substituents, a hypsochromic shift of the absorption compared to the monomer absorption in solution is observed due to the card stack like packing of the molecules in the solid state. By utilization of sterical demanding or flexible donor substituents, a zig-zag type packing is observed, leading to a bathochromical shift of the absorption. These packing motifs and spectral shifts with an offset of 0.93 eV of the H- and J-bands comply with the archetype examples of H- and J-aggregates from Kasha's exciton theory.}, subject = {Exziton}, language = {en} } @phdthesis{Mueller2017, author = {M{\"u}ller, Stephanie}, title = {Plant thermotolerance: The role of heat stress-induced triacylglycerols in \(Arabidopsis\) \(thaliana\)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152829}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Plants are exposed to high temperature, especially during hot summer days. Temperatures are typically lowest in the morning and reach a maximum in the afternoon. Plants can tolerate and survive short-term heat stress even on hot summer days. A. thaliana seedlings have been reported to tolerate higher temperatures for different time periods, a phenomenon that has been termed basal thermotolerance. In addition, plants have the inherent capacity to acclimate to otherwise lethal temperatures. Arabidopsis thaliana seedlings acclimate at moderately elevated temperatures between 32-38° C. During heat acclimation, a genetically programmed heat shock response (HSR) is triggered that is characterized by a rapid activation of heat shock transcription factors (HSFs), which trigger a massive accumulation of heat shock proteins that are chiefly involved in protein folding and protection. Although the HSF-triggered heat-shock response is well characterized, little is known about the metabolic adjustments during heat stress. The aim of this work was to get more insight into heat-responsive metabolism and its importance for thermotolerance. In order to identify the response of metabolites to elevated temperatures, global metabolite profiles of heat-acclimated and control seedlings were compared. Untargeted metabolite analyses revealed that levels of polyunsaturated triacylglycerols (TG) rapidly increase during heat acclimation. TG accumulation was found to be temperature-dependent in a temperature range from 32-50° C (optimum at 42° C). Heat-induced TG accumulation was localized in extra-chloroplastic compartments by chloroplast isolation as well as by fluorescence microscopy of A. thaliana cell cultures. Analysis of mutants deficient in all four HSFA1 master regulator genes or the HSFA2 gene revealed that TG accumulation occurred independently to HSF. Moreover, the TG response was not limited to heat stress since drought and salt stress (but not short-term osmotic, cold and high light stress) also triggered an accumulation of TGs. In order to reveal the origin of TG synthesis, lipid analysis was carried out. Heat-induced accumulation of TGs does not derive from massive de novo fatty acid (FA) synthesis. On the other hand, lipidomic analyses of A. thaliana seedlings indicated that polyunsaturated FA from thylakoid galactolipids are incorporated into cytosolic TGs during heat stress. This was verified by lipidomic analyses of A. thaliana fad7/8 transgenic seedlings, which displayed altered FA compositions of plastidic lipids. In addition, wild type A. thaliana seedlings displayed a rapid conversion of plastidic monogalactosyldiacylglycerols (MGDGs) into oligogalactolipids, acylated MGDGs and diacylglycerols (DGs). For TG synthesis, DG requires a FA from the acyl CoA pool or phosphatidylcholine (PC). Seedlings deficient in phospholipid:diacylglycerol acyltransferase1 (PDAT1) were unable to accumulate TGs following heat stress; thus PC appears to be the major FA donor for TGs during heat treatment. These results suggest that TG and oligogalactolipid accumulation during heat stress is driven by post-translationally regulated plastid lipid metabolism. TG accumulation following heat stress was found to increase basal thermotolerance. Pdat1 mutant seedlings were more sensitive to severe heat stress without prior acclimatization, as revealed by a more dramatic decline of the maximum efficiency of PSII and lower survival rate compared to wild type seedlings. In contrast, tgd1 mutants over-accumulating TGs and oligogalactolipids displayed a higher basal thermotolerance compared to wild type seedlings. These results therefore suggest that accumulation of TGs increases thermotolerance in addition to the genetically encoded heat shock response.}, subject = {Triglyceride}, language = {en} } @phdthesis{Beinicke2017, author = {Beinicke, Andrea}, title = {Career Construction Across the Life Span: Career Choice and Career Development}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117447}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {This dissertation contributes to deepen our understanding of constructs that play a key role in individuals' vocational career construction. In this regard, many previous studies have focused exclusively on a specific phase of an individual's career. Yet, modern societies require continuous investments in one's career to adapt to changing Environments throughout the life span. Consequently, this dissertation takes a broad approach to capture a wide spectrum of career construction processes. According to Super's (1990) developmental stage framework, individuals have to manage vocational developmental tasks corresponding to each of the developmental life stages in order to be career mature across the life span. As the two stages exploration and maintenance set the stage for individuals' future career pathways, they are especially important in individuals' vocational career construction. Therefore, both of them are addressed in this dissertation. By answering open research questions relevant to career choice in early career stages and to career development in later career stages, this dissertation contributes to the overarching goal of shedding more light on constructs relevant to individuals' vocational career construction processes across the life span. Beyond the results presented within each study's horizon, this dissertation aimed at offering practical guidance to career counselors, trainees, and training and development (T\&D) professionals. Career counselors and T\&D professionals are involved in guiding vocational career construction processes of individuals across the life span. Thus, on the one hand, this dissertation supports career counselors' work so that they can help deliberating individuals make optimal and effective career choices. On the other hand, this dissertation facilitates T\&D professionals' work so that they can effectively design and evaluate e-learning and classroom trainings in corporate educational settings. Identifying individuals' vocational interests combined with cognitive abilities through adequate test measures and maximizing success of learning and success of transfer through fostering evidence-based transfer support actions will help individuals adapt quickly to the changing nature of work environments in the 21st century and to continue to successfully construct careers across the life span.}, subject = {Karriere}, language = {en} } @phdthesis{Burger2017, author = {Burger, Valentin}, title = {Performance Evalution and Optimization of Content Delivery Networks}, issn = {1432-8801}, doi = {10.25972/OPUS-15276}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152769}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Content Delivery Networks (CDNs) are networks that distribute content in the Internet. CDNs are increasingly responsible for the largest share of traffic in the Internet. CDNs distribute popular content to caches in many geographical areas to save bandwidth by avoiding unnecessary multihop retransmission. By bringing the content geographically closer to the user, CDNs also reduce the latency of the services. Besides end users and content providers, which require high availability of high quality content, CDN providers and Internet Service Providers (ISPs) are interested in an efficient operation of CDNs. In order to ensure an efficient replication of the content, CDN providers have a network of (globally) distributed interconnected datacenters at different points of presence (PoPs). ISPs aim to provide reliable and high speed Internet access. They try to keep the load on the network low and to reduce cost for connectivity with other ISPs. The increasing number of mobile devices such as smart phones and tablets, high definition video content and high resolution displays result in a continuous growth in mobile traffic. This growth in mobile traffic is further accelerated by newly emerging services, such as mobile live streaming and broadcasting services. The steep increase in mobile traffic is expected to reach by 2018 roughly 60\% of total network traffic, the majority of which will be video. To handle the growth in mobile networks, the next generation of 5G mobile networks is designed to have higher access rates and an increased densification of the network infrastructure. With the explosion of access rates and number of base stations the backhaul of wireless networks will become congested. To reduce the load on the backhaul, the research community suggests installing local caches in gateway routers between the wireless network and the Internet, in base stations of different sizes, and in end-user devices. The local deployment of caches allows keeping the traffic within the ISPs network. The caches are organized in a hierarchy, where caches in the lowest tier are requested first. The request is forwarded to the next tier, if the requested object is not found. Appropriate evaluation methods are required to optimally dimension the caches dependent on the traffic characteristics and the available resources. Additionally methods are necessary that allow performance evaluation of backhaul bandwidth aggregation systems, which further reduce the load on the backhaul. This thesis analyses CDNs utilizing locally available resources and develops the following evaluations and optimization approaches: Characterization of CDNs and distribution of resources in the Internet, analysis and optimization of hierarchical caching systems with bandwidth constraints and performance evaluation of bandwidth aggregation systems.}, subject = {CDN-Netzwerk}, language = {en} } @phdthesis{Fischbach2017, author = {Fischbach, Martin Walter}, title = {Enhancing Software Quality of Multimodal Interactive Systems}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152723}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Multimodal interfaces (MMIs) are a promising human-computer interaction paradigm. They are feasible for a wide rang of environments, yet they are especially suited if interactions are spatially and temporally grounded with an environment in which the user is (physically) situated. Real-time interactive systems (RISs) are technical realizations for situated interaction environments, originating from application areas like virtual reality, mixed reality, human-robot interaction, and computer games. RISs include various dedicated processing-, simulation-, and rendering subsystems which collectively maintain a real-time simulation of a coherent application state. They thus fulfil the complex functional requirements of their application areas. Two contradicting principles determine the architecture of RISs: coupling and cohesion. On the one hand, RIS subsystems commonly use specific data structures for multiple purposes to guarantee performance and rely on close semantic and temporal coupling between each other to maintain consistency. This coupling is exacerbated if the integration of artificial intelligence (AI) methods is necessary, such as for realizing MMIs. On the other hand, software qualities like reusability and modifiability call for a decoupling of subsystems and architectural elements with single well-defined purposes, i.e., high cohesion. Systems predominantly favour performance and consistency over reusability and modifiability to handle this contradiction. They thus accept low maintainability in general and hindered scientific progress in the long-term. This thesis presents six semantics-based techniques that extend the established entity-component system (ECS) pattern and pose a solution to this contradiction without sacrificing maintainability: semantic grounding, a semantic entity-component state, grounded actions, semantic queries, code from semantics, and decoupling by semantics. The extension solves the ECS pattern's runtime type deficit, improves component granularity, facilitates access to entity properties outside a subsystem's component association, incorporates a concept to semantically describe behavior as complement to the state representation, and enables compatibility even between RISs. The presented reference implementation Simulator X validates the feasibility of the six techniques and may be (re)used by other researchers due to its availability under an open-source licence. It includes a repertoire of common multimodal input processing steps that showcase the particular adequacy of the six techniques for such processing. The repertoire adds up to the integrated multimodal processing framework miPro, making Simulator X a RIS platform with explicit MMI support. The six semantics-based techniques as well as the reference implementation are validated by four expert reviews, multiple proof of concept prototypes, and two explorative studies. Informal insights gathered throughout the design and development supplement this assessment in the form of lessons learned meant to aid future development in the area.}, subject = {Echtzeitsystem}, language = {en} } @phdthesis{Kuger2017, author = {Kuger, Fabian}, title = {Signal Formation Processes in Micromegas Detectors and Quality Control for large size Detector Construction for the ATLAS New Small Wheel}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152495}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {The Micromegas technology is one of the most successful modern gaseous detector concepts and widely utilized in nuclear and particle physics experiments. Twenty years of R \& D rendered the technology sufficiently mature to be selected as precision tracking detector for the New Small Wheel (NSW) upgrade of the ATLAS Muon spectrometer. This will be the first large scale application of Micromegas in one of the major LHC experiments. However, many of the fundamental microscopic processes in these gaseous detectors are still not fully understood and studies on several detector aspects, like the micromesh geometry, have never been addressed systematically. The studies on signal formation in Micromegas, presented in the first part of this thesis, focuses on the microscopic signal electron loss mechanisms and the amplification processes in electron gas interaction. Based on a detailed model of detector parameter dependencies, these processes are scrutinized in an iterating comparison between exper- imental results, theory prediction of the macroscopic observables and process simulation on the microscopic level. Utilizing the specialized detectors developed in the scope of this thesis as well as refined simulation algorithms, an unprecedented level of accuracy in the description of the microscopic processes is reached, deepening the understanding of the fundamental process in gaseous detectors. The second part is dedicated to the challenges arising with the large scale Micro- megas production for the ATLAS NSW. A selection of technological choices, partially influenced or determined by the herein presented studies, are discussed alongside a final report on two production related tasks addressing the detectors' core components: For the industrial production of resistive anode PCBs a detailed quality control (QC) and quality assurance (QA) scheme as well as the therefore required testing tools have been developed. In parallel the study on micromesh parameter optimization and production feasibility resulted in the selection of the proposed mesh by the NSW community and its full scale industrial manufacturing. The successful completion of both tasks were im- portant milestones towards the construction of large size Micromegas detectors clearing the path for NSW series production.}, subject = {Gasionisationsdetektor}, language = {en} } @phdthesis{Then2017, author = {Then, Patrick}, title = {Waveguide-based single molecule detection in flow}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140548}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {In this work fluorescence-based single molecule detection at low concetration is investigated, with an emphasis on the usage of active transport and waveguides. Active transport allows to overcome the limits of diffusion-based systems in terms of the lowest detectable threshold of concentration. The effect of flow in single molecule experiments is investigated and a theoretical model is derived for laminar flow. Waveguides on the other hand promise compact detection schemes and show great potential for their possible integration into lab-on-a-chip applications. Their properties in single molecule experiments are analyzed with help of a method based on the reciprocity theorem of electromagnetic theory.}, subject = {Optik}, language = {en} }