@techreport{Winkelmann2015, type = {Working Paper}, author = {Winkelmann, Axel}, title = {Proceedings of the Doctoral Consortium WI 2015}, editor = {Winkelmann, Axel}, issn = {2199-0328}, doi = {10.25972/OPUS-11171}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111715}, pages = {213}, year = {2015}, abstract = {Bereits seit Anfang der 1990er Jahre wird jungen Wissenschaftlern im Vorfeld der Tagung "Wirtschaftsinformatik" ein Doctoral Consortium als unterst{\"u}tzendes Forum angeboten. Diese Einrichtung wurde auch zur gr{\"o}ßten Internationalen Konferenz der Wirtschaftsinformatik, der WI 2015 in Osnabr{\"u}ck fortgef{\"u}hrt. Dieser Band fasst die zum Vortag ausgew{\"a}hlten Beitr{\"a}ge zusammen.}, subject = {Wirtschaftsinformatik}, language = {en} } @phdthesis{Muenz2015, author = {M{\"u}nz, Thomas Sebastian}, title = {Aspects of neuronal plasticity in the mushroom body calyx during adult maturation in the honeybee Apis mellifera}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111611}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Division of labor represents a major advantage of social insect communities that accounts for their enormous ecological success. In colonies of the honeybee, Apis mellifera, division of labor comprises different tasks of fertile queens and drones (males) and, in general, sterile female workers. Division of labor also occurs among workers in form of an age-related polyethism. This helps them to deal with the great variety of tasks within the colony. After adult eclosion, workers spend around three weeks with various duties inside the hive such as tending the brood or cleaning and building cells. After this period workers switch to outdoor tasks and become foragers collecting nectar, pollen and water. With this behavioral transition, workers face tremendous changes in their sensory environment. In particular, visual sensory stimuli become important, but also the olfactory world changes. Foragers have to perform a completely new behavioral repertoire ranging from long distance navigation based on landmark orientation and polarized-skylight information to learning and memory tasks associated with finding profitable food sources. However, behavioral maturation is not a purely age-related internal program associated with a change, for example, in juvenile hormone titers. External factors such as primer pheromones like the brood pheromone or queen mandibular pheromone can modulate the timing of this transition. In this way colonies are able to flexibly adjust their work force distribution between indoor and outdoor tasks depending on the actual needs of the colony. Besides certain physiological changes, mainly affecting glandular tissue, the transition from indoor to outdoor tasks requires significant adaptations in sensory and higher-order integration centers of the brain. The mushroom bodies integrate olfactory, visual, gustatory and mechanosensory information. Furthermore, they play important roles in learning and memory processes. It is therefore not surprising that the mushroom bodies, in particular their main input region, the calyx, undergo volumetric neuronal plasticity. Similar to behavioral maturation, plastic changes of the mushroom bodies are associated with age, but are also to be affected by modulating factors such as task and experience. In my thesis, I analyzed in detail the neuronal processes underlying volumetric plasticity in the mushroom body. Immunohistochemical labeling of synaptic proteins combined with quantitative 3D confocal imaging revealed that the volume increase of the mushroom body calyx is largely caused by the growth of the Kenyon cell dendritic network. This outgrowth is accompanied by changes in the synaptic architecture of the mushroom body calyx, which is organized in a distinct pattern of synaptic complexes, so called microglomeruli. During the first week of natural adult maturation microglomeruli remain constant in total number. With subsequent behavioral transition from indoor duties to foraging, microglomeruli are pruned while the Kenyon cell dendritic network is still growing. As a result of these processes, the mushroom body calyx neuropil volume enlarges while the total number of microgloumeruli becomes reduced in foragers compared to indoor workers. In the visual subcompartments (calyx collar) this process is induced by visual sensory stimuli as the beginning of pruning correlates with the time window when workers start their first orientation flights. The high level of analysis of cellular and subcellular process underlying structural plasticity of the mushroom body calyx during natural maturation will serve as a framework for future investigations of behavioral plasticity in the honeybee. The transition to foraging is not purely age-dependent, but gets modulated, for example, by the presence of foragers. Ethyl oleate, a primer pheromone that is present only in foragers, was shown to delay the onset of foraging in nurse bees. Using artificial application of additional ethyl oleate in triple cohort colonies, I tested whether it directly affects adult neuronal plasticity in the visual input region of the mushroom body calyx. As the pheromonal treatment failed to induce a clear behavioral phenotype (delayed onset of foraging) it was not possible to show a direct link between the exposure to additional ethyl oleate and neuronal plasticity in mushroom body calyx. However, the general results on synaptic maturation confirmed my data of natural maturation processes in the mushroom body calyx. Given the result that dendritic plasticity is a major contributor to neuronal plasticity in the mushroom body calyx associated with division of labor, the question arose which proteins could be involved in mediating these effects. Calcium/calmodulin-dependent protein kinase II (CaMKII) especially in mammals, but also in insects (Drosophila, Cockroach), was shown to be involved in facilitating learning and memory processes like long-term synaptic potentiation. In addition to presynaptic effects, the protein was also revealed to directly interact with cytoskeleton elements in the postsynapse. It therefore is a likely candidate to mediate structural synaptic plasticity. As part of my thesis, the presence and distribution of CaMKII was analyzed, and the results showed that the protein is highly concentrated in a distinct subpopulation of the mushroom body intrinsic neurons, the noncompact Kenyon cells. The dendritic network of this population arborizes in two calyx subregions: one receiving mainly olfactory input - the lip - and the collar receiving visual input. This distribution pattern did not change with age or task. The high concentration of CaMKII in dendritic spines and its overlap with f-actin indicates that CaMKII could be a key player inducing structural neuronal plasticity associated with learning and memory formation and/or behavioral transitions related to division of labor. Interestingly CaMKII immunoreactivity was absent in the basal ring, another subregion of the mushroom body calyx formed almost exclusively by the inner compact Kenyon cells and known to receive combined visual and olfactory input. This indicates differences of this mushroom body subregion regarding the molecular mechanisms controlling plastic changes in corresponding Kenyon cells. How is timing of behavioral and neuronal plasticity regulated? The primer pheromone ethyl oleate was found in high concentrations on foragers and was shown to influence behavioral maturation by delaying the onset of foraging when artificially applied in elevated concentrations. But how is ethyl oleate transferred and how does it shift the work force distribution between indoor and outdoor tasks? Previous work showed that ethyl oleate concentrations are highest in the honeycrop of foragers and suggested that it is transferred and communicated inside the colony via trophallaxis. The results of this thesis however clearly show, that ethyl oleate was not present inside the honey crop or the regurgitate, but rather in the surrounding tissue of the honey crop. As additionally the second highest concentration of ethyl oleate was measured on the surface of the cuticle of forgers, trophallaxis was ruled out as a mode of transmission. Neurophysiological measurements at the level of the antennae (electroantennogram recordings) and the first olfactory neuropil (calcium imaging of activity in the antennal lobe) revealed that the primer pheromone ethyl oleate is received and processed as an olfactory stimulus. Appetitive olfactory conditioning using the proboscis extension response as a behavioral paradigm showed that ethyl oleate can be associated with a sugar reward. This indicates that workers are able to perceive, learn and memorize the presence of this pheromone. As ethyl oleate had to be presented by a heated stimulation device at close range, it can be concluded that this primer pheromone acts via close range/contact chemoreception through the olfactory system. This is also supported by previous behavioral observations. Taken together, the findings presented in this thesis revealed structural changes in the synaptic architecture of the mushroom body calyx associated with division of labor. For the primer pheromone ethyl oleate, which modulates the transition from nursing to foraging, the results clearly showed that it is received via the olfactory system and presumably acts via this pathway. However, manipulation experiments did not indicate a direct effect of ethyl oleate on synaptic plasticity. At the molecular level, CaMKII is a prime candidate to mediate structural synaptic plasticity in the mushroom body calyx. Future combined structural and functional experiments are needed to finally link the activity of primer pheromones like ethyl oleate to the molecular pathways mediating behavioral and synaptic plasticity associated with division of labor in Apis mellifera. The here identified underlying processes will serve as excellent models for a general understanding of fundamental mechanisms promoting behavioral plasticity.}, subject = {Biene}, language = {en} } @phdthesis{Wamser2015, author = {Wamser, Florian}, title = {Performance Assessment of Resource Management Strategies for Cellular and Wireless Mesh Networks}, issn = {1432-8801}, doi = {10.25972/OPUS-11151}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111517}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {The rapid growth in the field of communication networks has been truly amazing in the last decades. We are currently experiencing a continuation thereof with an increase in traffic and the emergence of new fields of application. In particular, the latter is interesting since due to advances in the networks and new devices, such as smartphones, tablet PCs, and all kinds of Internet-connected devices, new additional applications arise from different areas. What applies for all these services is that they come from very different directions and belong to different user groups. This results in a very heterogeneous application mix with different requirements and needs on the access networks. The applications within these networks typically use the network technology as a matter of course, and expect that it works in all situations and for all sorts of purposes without any further intervention. Mobile TV, for example, assumes that the cellular networks support the streaming of video data. Likewise, mobile-connected electricity meters rely on the timely transmission of accounting data for electricity billing. From the perspective of the communication networks, this requires not only the technical realization for the individual case, but a broad consideration of all circumstances and all requirements of special devices and applications of the users. Such a comprehensive consideration of all eventualities can only be achieved by a dynamic, customized, and intelligent management of the transmission resources. This management requires to exploit the theoretical capacity as much as possible while also taking system and network architecture as well as user and application demands into account. Hence, for a high level of customer satisfaction, all requirements of the customers and the applications need to be considered, which requires a multi-faceted resource management. The prerequisite for supporting all devices and applications is consequently a holistic resource management at different levels. At the physical level, the technical possibilities provided by different access technologies, e.g., more transmission antennas, modulation and coding of data, possible cooperation between network elements, etc., need to be exploited on the one hand. On the other hand, interference and changing network conditions have to be counteracted at physical level. On the application and user level, the focus should be on the customer demands due to the currently increasing amount of different devices and diverse applications (medical, hobby, entertainment, business, civil protection, etc.). The intention of this thesis is the development, investigation, and evaluation of a holistic resource management with respect to new application use cases and requirements for the networks. Therefore, different communication layers are investigated and corresponding approaches are developed using simulative methods as well as practical emulation in testbeds. The new approaches are designed with respect to different complexity and implementation levels in order to cover the design space of resource management in a systematic way. Since the approaches cannot be evaluated generally for all types of access networks, network-specific use cases and evaluations are finally carried out in addition to the conceptual design and the modeling of the scenario. The first part is concerned with management of resources at physical layer. We study distributed resource allocation approaches under different settings. Due to the ambiguous performance objectives, a high spectrum reuse is conducted in current cellular networks. This results in possible interference between cells that transmit on the same frequencies. The focus is on the identification of approaches that are able to mitigate such interference. Due to the heterogeneity of the applications in the networks, increasingly different application-specific requirements are experienced by the networks. Consequently, the focus is shifted in the second part from optimization of network parameters to consideration and integration of the application and user needs by adjusting network parameters. Therefore, application-aware resource management is introduced to enable efficient and customized access networks. As indicated before, approaches cannot be evaluated generally for all types of access networks. Consequently, the third contribution is the definition and realization of the application-aware paradigm in different access networks. First, we address multi-hop wireless mesh networks. Finally, we focus with the fourth contribution on cellular networks. Application-aware resource management is applied here to the air interface between user device and the base station. Especially in cellular networks, the intensive cost-driven competition among the different operators facilitates the usage of such a resource management to provide cost-efficient and customized networks with respect to the running applications.}, subject = {Leistungsbewertung}, language = {en} } @phdthesis{Stoll2015, author = {Stoll, Georg}, title = {Identification of the mRNA-associated TOP3β- TDRD3-FMRP (TTF) -complex and its implication for neurological disorders}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111440}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {The propagation of the genetic information into proteins is mediated by messenger- RNA (mRNA) intermediates. In eukaryotes mRNAs are synthesized by RNA- Polymerase II and subjected to translation after various processing steps. Earlier it was suspected that the regulation of gene expression occurs primarily on the level of transcription. In the meantime it became evident that the contribution of post- transcriptional events is at least equally important. Apart from non-coding RNAs and metabolites, this process is in particular controlled by RNA-binding proteins, which assemble on mRNAs in various combinations to establish the so-called "mRNP- code". In this thesis a so far unknown component of the mRNP-code was identified and characterized. It constitutes a hetero-trimeric complex composed of the Tudor domain-containing protein 3 (TDRD3), the fragile X mental retardation protein (FMRP) and the Topoisomerase III beta (TOP3β) and was termed TTF (TOP3β-TDRD3-FMRP) -complex according to its composition. The presented results also demonstrate that all components of the TTF-complex shuttle between the nucleus and the cytoplasm, but are predominantly located in the latter compartment under steady state conditions. Apart from that, an association of the TTF-complex with fully processed mRNAs, not yet engaged in productive translation, was detected. Hence, the TTF-complex is a component of „early" mRNPs. The defined recruitment of the TTF-complex to these mRNPs is not based on binding to distinct mRNA sequence-elements in cis, but rather on an interaction with the so-called exon junction complex (EJC), which is loaded onto the mRNA during the process of pre-mRNA splicing. In this context TDRD3 functions as an adapter, linking EJC, FMRP and TOP3β on the mRNP. Moreover, preliminary results suggest that epigenetic marks within gene promoter regions predetermine the transfer of the TTF-complex onto its target mRNAs. Besides, the observation that TOP3β is able to catalytically convert RNA-substrates disclosed potential activities of the TTF-complex in mRNA metabolism. In combination with the already known functions of FMRP, this finding primarily suggests that the TTF-complex controls the translation of bound mRNAs. In addition to its role in mRNA metabolism, the TTF-complex is interesting from a human genetics perspective as well. It was demonstrated in collaboration with researchers from Finland and the US that apart from FMRP, which was previously linked to neurocognitive diseases, also TOP3β is associated with neurodevelopmental disorders. Understanding the function of the TTF-complex in mRNA metabolism might hence provide important insight into the etiology of these diseases.}, subject = {Messenger-RNS}, language = {en} } @phdthesis{Thies2015, author = {Thies, Elena-Daphne Doroth{\´e}e}, title = {Die Prognose des differenzierten Schilddr{\"u}senkarzinoms in Abh{\"a}ngigkeit von der zum Erreichen eines erkrankungsfreien Zustands ben{\"o}tigten Zahl der I-131-Therapien}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110981}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Ziel: Absch{\"a}tzung der Risiken des Rezidivs des differenzierten Schilddr{\"u}senkarzinoms, der Karzinom-bedingten Mortalit{\"a}t und der Karzinom-bedingten Reduktion der Lebenserwartung in Abh{\"a}ngigkeit von der Anzahl der zum Erreichen eines krankheitsfreien Zustands ben{\"o}tigten I-131-Therapien (Radioiodtherapien) und der f{\"u}r die Krankheitsfreiheit ben{\"o}tigten kumulativen Aktivit{\"a}t. Methoden: Analyse anhand von in der W{\"u}rzburger Schilddr{\"u}senkarzinom-Datenbank erfassten Verlaufsdaten unter Ber{\"u}cksichtigung eigener zus{\"a}tzlicher Erhebungen zum follow-up.von 896 Patienten, die nach einer oder mehreren Radioiodtherapien im Therapieverlauf Erkrankungsfreiheit erreichten (negative TSH-stimulierte Thyreoglobulin-Messung in Kombination mit einer negativen I-131-Ganzk{\"o}rperszintigraphie). Ergebnisse: Die erfassbare Nachsorgedauer betrug in Median 9.0 Jahre (Spannbreite 0.1-31.8 Jahre). Rezidiv-Raten nach 5 und 10 Jahren und am Ende der Nachsorge betrugen 1,0±0,3\%, 4,0±0,7\% und 6,2±1,1\%. Die Schilddr{\"u}senkarzinom-bedingte Sterberate betrug jeweils 0,1±0,1\%, 0,5±0,3\% und 3,4±1,1\%. Mit einer zunehmenden Anzahl von ben{\"o}tigten Radioiodtherapien nahm die Rezidivrate zu (p=0.001). Die Schilddr{\"u}senkarzinom-bedingte Sterblichkeitsrate ist ab 4 ben{\"o}tigten Radioiodtherapien erh{\"o}ht. Bei Patienten, die nach einer Radioiodtherapie krankheitsfrei waren, finden sich zwischen Niedrig- und Hochrisikopatienten keine Unterschiede bez{\"u}glich Rezidiv- und Sterblichkeitsrate. Bei Patienten, die zwei Radioiodtherapien ben{\"o}tigten, waren Rezidiv- und Sterblichkeitsrate der Hochrisikopatienten erh{\"o}ht. Bez{\"u}glich der kumulativ ben{\"o}tigten Aktivit{\"a}t zeigten sich nur bei Patienten, die eine kumulative Aktivit{\"a}t von {\"u}ber 22,2 GBq ben{\"o}tigten, erh{\"o}hte Rezidiv- und Sterberaten. Im vorliegenden Studienkollektiv mit einer inh{\"a}rent guten Prognose zeigte sich eine uneingeschr{\"a}nkte Lebenserwartung unabh{\"a}ngig von der ben{\"o}tigen Anzahl der Radioiodtherapien oder der ben{\"o}tigten kumulativen Aktivit{\"a}t. Fazit: Falls mehr als eine Radioiodtherapie oder eine hohe kumulative I-131 Aktivit{\"a}t ben{\"o}tigt wird, um einen krankheitsfreien Zustand zu erreichen, muss mit einer Rezidiv- und Schilddr{\"u}senkarzinom-bedingten Sterblichkeits-Rate gerechnet werden, vor allem bei Hochrisikopatienten.}, subject = {Differentiated thyroid carcinoma}, language = {de} } @phdthesis{Nguyen2015, author = {Nguyen, Thanh Nam}, title = {A model system for carbohydrates interactions on single-crystalline Ru surfaces}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111485}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {In this thesis, I present a model system for carbohydrate interactions with single-crystalline Ru surfaces. Geometric and electronic properties of copper phthalocyanine (CuPc) on top of graphene on hexagonal Ru(0001), rectangular Ru(10-10) and vicinal Ru(1,1,-2,10) surfaces have been studied. First, the Fermi surfaces and band structures of the three Ru surfaces were investigated by high-resolution angle-resolved photoemission spectroscopy. The experimental data and theoretical calculations allow to derive detailed information about the momentum-resolved electronic structure. The results can be used as a reference to understand the chemical and catalytic properties of Ru surfaces. Second, graphene layers were prepared on the three different Ru surfaces. Using low-energy electron diffraction and scanning tunneling microscopy, it was found that graphene can be grown in well-ordered structures on all three surfaces, hexagonal Ru(0001), rectangular Ru(10-10) and vicinal Ru(1,1,-2,10), although they have different surface symmetries. Evidence for a strong interaction between graphene and Ru surfaces is a 1.3-1.7e V increase in the graphene pi-bands binding energy with respect to free-standing graphene sheets. This energy variation is due to the hybridization between the graphene pi bands and the Ru 4d electrons, while the lattice mismatch does not play an important role in the bonding between graphene and Ru surfaces. Finally, the geometric and electronic structures of CuPc on Ru(10-10), graphene/Ru(10-10), and graphene/Ru(0001) have been studied in detail. CuPc molecules can be grown well-ordered on Ru(10-10) but not on Ru(0001). The growth of CuPc on graphene/Ru(10-10) and Ru(0001) is dominated by the Moire pattern of graphene. CuPc molecules form well-ordered structures with rectangular unit cells on graphene/Ru(10-10) and Ru(0001). The distance of adjacent CuPc molecules is 1.5 and 1.3 nm on graphene/Ru(0001) and 1.54 and 1.37 nm on graphene/Ru(10-10). This indicates that the molecule-substrate interaction dominates over the intermolecular interaction for CuPc molecules on graphene/Ru(10-10) and graphene/Ru(0001).}, subject = {Ruthenium}, language = {en} } @phdthesis{Mohammadi2015, author = {Mohammadi, Masoumeh}, title = {Analysis of discretization schemes for Fokker-Planck equations and related optimality systems}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111494}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {The Fokker-Planck (FP) equation is a fundamental model in thermodynamic kinetic theories and statistical mechanics. In general, the FP equation appears in a number of different fields in natural sciences, for instance in solid-state physics, quantum optics, chemical physics, theoretical biology, and circuit theory. These equations also provide a powerful mean to define robust control strategies for random models. The FP equations are partial differential equations (PDE) describing the time evolution of the probability density function (PDF) of stochastic processes. These equations are of different types depending on the underlying stochastic process. In particular, they are parabolic PDEs for the PDF of Ito processes, and hyperbolic PDEs for piecewise deterministic processes (PDP). A fundamental axiom of probability calculus requires that the integral of the PDF over all the allowable state space must be equal to one, for all time. Therefore, for the purpose of accurate numerical simulation, a discretized FP equation must guarantee conservativeness of the total probability. Furthermore, since the solution of the FP equation represents a probability density, any numerical scheme that approximates the FP equation is required to guarantee the positivity of the solution. In addition, an approximation scheme must be accurate and stable. For these purposes, for parabolic FP equations on bounded domains, we investigate the Chang-Cooper (CC) scheme for space discretization and first- and second-order backward time differencing. We prove that the resulting space-time discretization schemes are accurate, conditionally stable, conservative, and preserve positivity. Further, we discuss a finite difference discretization for the FP system corresponding to a PDP process in a bounded domain. Next, we discuss FP equations in unbounded domains. In this case, finite-difference or finite-element methods cannot be applied. By employing a suitable set of basis functions, spectral methods allow to treat unbounded domains. Since FP solutions decay exponentially at infinity, we consider Hermite functions as basis functions, which are Hermite polynomials multiplied by a Gaussian. To this end, the Hermite spectral discretization is applied to two different FP equations; the parabolic PDE corresponding to Ito processes, and the system of hyperbolic PDEs corresponding to a PDP process. The resulting discretized schemes are analyzed. Stability and spectral accuracy of the Hermite spectral discretization of the FP problems is proved. Furthermore, we investigate the conservativity of the solutions of FP equations discretized with the Hermite spectral scheme. In the last part of this thesis, we discuss optimal control problems governed by FP equations on the characterization of their solution by optimality systems. We then investigate the Hermite spectral discretization of FP optimality systems in unbounded domains. Within the framework of Hermite discretization, we obtain sparse-band systems of ordinary differential equations. We analyze the accuracy of the discretization schemes by showing spectral convergence in approximating the state, the adjoint, and the control variables that appear in the FP optimality systems. To validate our theoretical estimates, we present results of numerical experiments.}, subject = {Fokker-Planck-Gleichung}, language = {en} } @phdthesis{Kuhtz2015, author = {Kuhtz, Juliane}, title = {Epimutationen humaner Keimzellen und Infertilit{\"a}t}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-108248}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Infertilit{\"a}t stellt in unserer heutigen Gesellschaft ein zunehmendes Problem dar. Bei der Suche nach den der Infertilit{\"a}t zugrunde liegenden Ursachen ger{\"a}t immer mehr die Epigenetik in den Fokus. Epigenetische Prozesse sind nicht nur in die Embryo-nalentwicklung und Wachstumsprozesse des Kindes involviert, sondern auch in korrekte Funktionsweisen von Gameten. St{\"o}rungen k{\"o}nnen die Fertilit{\"a}t beeintr{\"a}ch-tigen. Eine besondere Rolle spielen gepr{\"a}gte Gene, die auf einem ihrer Allele, je nach parentaler Herkunft, ein Imprint in Form von DNA-Methylierung tragen. Fehl-regulationen solcher gepr{\"a}gter Gene k{\"o}nnen zu Imprinting-Erkrankungen f{\"u}hren. Seit Einf{\"u}hrung der In-vitro-Fertilisation (IVF) wurden verschiedene assistierte Re-produktionstechniken (ART) entwickelt, um infertilen Paaren zu helfen. Die Sicher-heit dieser Techniken ist nicht abschließend gekl{\"a}rt. Immer wieder wird von nach ART-Behandlung geh{\"a}uft auftretenden Imprinting-Erkrankungen berichtet. Diese Erkrankungen stehen jedoch eher in Zusammenhang mit der zugrunde liegenden Infertilit{\"a}t, als mit ART selbst. Dennoch ist es notwendig zu untersuchen inwieweit sich ART eventuell auf den Gesundheitszustand dieser Kinder auswirken k{\"o}nnte. In der hier vorgelegten Arbeit wurde der Zusammenhang von Epigenetik, Infertilit{\"a}t und ART von verschiedenen Standpunkten aus beleuchtet. In humanen Spermien wurde die DNA-Methylierung verschiedener gepr{\"a}gter Gene hinsichtlich Epimutationen untersucht. ICSI (intracytoplasmatic sperm injection) und IMSI (intracytoplasmic morphologically selected sperm injection) sind verschiedene Techniken zur Selektion von Spermien f{\"u}r eine ART-Behandlung. Hier wurde un-tersucht, ob IMSI epigenetisch bessere Spermien selektiert als die konventionelle ICSI-Methode. Außerdem ist bekannt, dass in Spermienk{\"o}pfen fertiler und infertiler M{\"a}nner Vakuolen vorkommen k{\"o}nnen, deren epigenetische Bedeutung jedoch un-bekannt ist. Ob diese Vakuolen in Zusammenhang mit Epimutationen stehen k{\"o}nn-ten, wurde ebenfalls {\"u}berpr{\"u}ft. Dazu wurde bisulfitkonvertierte DNA weniger Sper-mien (11 je Probe) mithilfe der Limiting Dilution (LD)-Technik und Pyrosequenzie-rung analysiert. Insgesamt standen 880 Spermien f{\"u}r diese Untersuchung zur Ver-f{\"u}gung. Es konnte kein Unterschied zwischen IMSI- und ICSI-selektierten Spermien gefunden werden. Vorhandene Vakuolen im Spermienkopf beeintr{\"a}chtigten nicht die DNA-Methylierung der Gene hGTL2, hLIT1 und hPEG3. Ein weiteres Projekt befasste sich mit der Frage, inwieweit die Technik der In-vitro-Maturation (IVM) DNA-Methylierung in humanen Oocyten beeinflussen k{\"o}nnte. Bisulfitkonvertierte DNA einzelner humaner Oocyten wurde mit LD und Pyrose-quenzierung analysiert. Verglichen wurden IVM und in vivo gereifte Oocyten. Hier-f{\"u}r standen 139 Oocyten zur Verf{\"u}gung, wovon 90 mittels IVM und 49 in vivo gereift waren. Untersucht wurden vier gepr{\"a}gte Gene (hGTL2, hLIT1, hPEG3 und hSNRPN) und drei nicht gepr{\"a}gte Gene (hDNMT3Lo, hNANOG und hOCT4). Es konnten keine IVM-bedingten Epimutationen gefunden werden. Im dritten Projekt wurde untersucht, ob sich die DNA-Methylierung normaler Sper-mien von Spermien aus Oligozoospermie-Asthenozoospermie-Teratozoospermie (OAT)-Syndrom-Patienten unterscheidet. Eine weitere Frage war, ob Epimutationen einen Einfluss auf den ART-Ausgang haben. Untersucht wurden 54 Spermienpro-ben von Paaren in ART-Behandlung. Zur Untersuchung der DNA-Methylierungsmuster der gepr{\"a}gten Gene hGTL2 und hPEG3 sowie der beiden nicht gepr{\"a}gten Pluripotenzgene hNANOG und hOCT4 wurde die Methode Deep Bisulfite Sequencing (DBS) verwendet. Dies ist eine Next Generation Sequencing (NGS)-Technik, angewandt an bisulfitkonvertierter DNA. Diese Technik erm{\"o}glicht es mehrere Proben sowie Gene gleichzeitig zu analysieren. Es zeigte sich, dass OAT-Spermien, die zu einer Lebendgeburt gef{\"u}hrt hatten, sich epigenetisch nicht von normalen Spermien unterschieden. Besonders viele Epimutationen konnten hingegen in OAT-Spermien gefunden werden, die zu keiner Schwangerschaft ge-f{\"u}hrt hatten. Zwischen Spermien die zu einer Lebendgeburt oder keiner Schwan-gerschaft gef{\"u}hrt hatten, zeigten sich Unterschiede in der H{\"a}ufigkeit von hGTL2-Epimutationen. {\"U}ber die H{\"a}ufigkeit von Epimutationen konnte eine pr{\"a}diktive Aus-sage zum ART-Ausgang getroffen werden. Zusammenfassend konnte in dieser Arbeit festgestellt werden, dass sich eine H{\"a}u-fung von Epimutationen darauf auswirkt, ob eine Schwangerschaft erreicht werden kann oder nicht. Diese Epimutationen liegen bereits im parentalen Genom vor. Sie werden nicht durch ART verursacht. Allerdings muss man Techniken finden, mit denen man Gameten mit m{\"o}glichst wenig Epimutationen selektiert, um eine {\"U}ber-tragung solcher auf das Kind zu verhindern.}, subject = {Epigenetik}, language = {de} } @misc{OPUS4-11154, title = {einBlick - Ausgabe 11 - 24. M{\"a}rz 2015}, volume = {11/2015}, organization = {Julius-Maximilians-Universit{\"a}t W{\"u}rzburg}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111540}, year = {2015}, abstract = {Nachrichten aus der Julius-Maximilians-Universit{\"a}t W{\"u}rzburg}, subject = {W{\"u}rzburg}, language = {de} } @inproceedings{FlandersJannidis2015, author = {Flanders, Julia and Jannidis, Fotis}, title = {Knowledge Organization and Data Modeling in the Humanities}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111270}, year = {2015}, abstract = {Based on the results of a 3-day workshop at the Brown University (2012) this white paper tries to sum up important topics and problems which came up in the presentations and discussions and to outline some general aspects of data modeling in digital humanities. Starting with an attempt to define data modeling it introduces distinctions like curation-driven vs. research-driven for a more general description of data modeling. The second part discusses specific problems and challenges of data modeling in the Humanities, while the third part outlines practical aspects, like the creation of data models or their evaluation.}, subject = {Digital Humanities}, language = {en} }