@phdthesis{Gruendler2018, author = {Gr{\"u}ndler, Klaus}, title = {A Contribution to the Empirics of Economic Development - The Role of Technology, Inequality, and the State}, edition = {1. Auflage}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, isbn = {978-3-95826-072-6 (Print)}, doi = {10.25972/WUP-978-3-95826-073-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141520}, school = {W{\"u}rzburg University Press}, pages = {300}, year = {2018}, abstract = {This dissertation contributes to the empirical analysis of economic development. The continuing poverty in many Sub-Saharan-African countries as well as the declining trend in growth in the advanced economies that was initiated around the turn of the millennium raises a number of new questions which have received little attention in recent empirical studies. Is culture a decisive factor for economic development? Do larger financial markets trigger positive stimuli with regard to incomes, or is the recent increase in their size in advanced economies detrimental to economic growth? What causes secular stagnation, i.e. the reduction in growth rates of the advanced economies observable over the past 20 years? What is the role of inequality in the growth process, and how do governmental attempts to equalize the income distribution affect economic development? And finally: Is the process of democratization accompanied by an increase in living standards? These are the central questions of this doctoral thesis. To facilitate the empirical analysis of the determinants of economic growth, this dissertation introduces a new method to compute classifications in the field of social sciences. The approach is based on mathematical algorithms of machine learning and pattern recognition. Whereas the construction of indices typically relies on arbitrary assumptions regarding the aggregation strategy of the underlying attributes, utilization of Support Vector Machines transfers the question of how to aggregate the individual components into a non-linear optimization problem. Following a brief overview of the theoretical models of economic growth provided in the first chapter, the second chapter illustrates the importance of culture in explaining the differences in incomes across the globe. In particular, if inhabitants have a lower average degree of risk-aversion, the implementation of new technology proceeds much faster compared with countries with a lower tendency towards risk. However, this effect depends on the legal and political framework of the countries, their average level of education, and their stage of development. The initial wealth of individuals is often not sufficient to cover the cost of investments in both education and new technologies. By providing loans, a developed financial sector may help to overcome this shortage. However, the investigations in the third chapter show that this mechanism is dependent on the development levels of the economies. In poor countries, growth of the financial sector leads to better education and higher investment levels. This effect diminishes along the development process, as intermediary activity is increasingly replaced by speculative transactions. Particularly in times of low technological innovation, an increasing financial sector has a negative impact on economic development. In fact, the world economy is currently in a phase of this kind. Since the turn of the millennium, growth rates in the advanced economies have experienced a multi-national decline, leading to an intense debate about "secular stagnation" initiated at the beginning of 2015. The fourth chapter deals with this phenomenon and shows that the growth potentials of new technologies have been gradually declining since the beginning of the 2000s. If incomes are unequally distributed, some individuals can invest less in education and technological innovations, which is why the fifth chapter identifies an overall negative effect of inequality on growth. This influence, however, depends on the development level of countries. While the negative effect is strongly pronounced in poor economies with a low degree of equality of opportunity, this influence disappears during the development process. Accordingly, redistributive polices of governments exert a growth-promoting effect in developing countries, while in advanced economies, the fostering of equal opportunities is much more decisive. The sixth chapter analyzes the growth effect of the political environment and shows that the ambiguity of earlier studies is mainly due to unsophisticated measurement of the degree of democratization. To solve this problem, the chapter introduces a new method based on mathematical algorithms of machine learning and pattern recognition. While the approach can be used for various classification problems in the field of social sciences, in this dissertation it is applied for the problem of democracy measurement. Based on different country examples, the chapter shows that the resulting SVMDI is superior to other indices in modeling the level of democracy. The subsequent empirical analysis emphasizes a significantly positive growth effect of democracy measured via SVMDI.}, subject = {Wirtschaftsentwicklung}, language = {en} } @phdthesis{Popp2018, author = {Popp, Michael}, title = {Mechanisms of platelet activation and receptor regulation in genetically modified mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135494}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {This work summarizes the results of studies on several major aspects of platelet activation and platelet receptor regulation. Therefore, this thesis is divided into four parts. Platelet activation and aggregation at sites of vascular injury is critical to prevent excessive blood loss, but may also lead to life-threatening ischemic disease states, such as myocardial infarction and stroke. Agonist-induced elevation in cytosolic Ca2+ concentrations is essential for platelet activation in hemostasis and thrombosis. The principal route of Ca2+ influx in platelets is store-operated calcium entry (SOCE). The calcium sensor molecule stromal interaction molecule 1 (STIM1) regulates SOCE by activating the membrane calcium channel protein Orai1, but the exact mechanisms of this interaction are not fully understood. Using affinity chromatography to screen for STIM1 interacting proteins in platelets, bridging integrator 2 (BIN2), an adapter protein belonging to the family of BAR proteins that is mainly expressed in the hematopoietic system, was identified. Newly generated BIN2 KO mice were viable and fertile but their platelets displayed markedly impaired SOCE in response to thapsigargin (TG) as well as agonists acting on immunoreceptor tyrosine-based activation motif (ITAM) or G protein-coupled receptors. This SOCE defect resulted in impaired (hem)ITAM induced platelet activation, aggregate formation under flow and procoagulant activity. As a consequence, mice lacking BIN2 in platelets were protected from occlusive arterial thrombus formation and thrombo-inflammatory cerebral infarct progression in a model of experimental stroke. These results identify BIN2 as a critical regulator of platelet SOCE in thrombosis and thrombo-inflammatory disease. Integrin αIIbβ3 plays a central role in the adhesion and aggregation of platelets. Integrin activation requires the transmission of a signal from the small cytoplasmic tails of the α or β subunit to the large extracellular domains resulting in conformational changes of the extracellular domains to enable ligand binding. It was hypothesized that Hic-5 is a novel regulator of integrin αIIbβ3 activation in mice. As demonstrated in the second part of this thesis, lack of Hic-5 had no detectable effect on platelet integrin activation and function in vitro and in vivo under all tested conditions. These results indicate that Hic-5 is dispensable for integrin αIIbβ3 activation and consequently for arterial thrombosis and hemostasis in mice. The Rho GTPase family members RhoA and Rac1 play major roles in platelet activation at sites of vascular injury. Little is known about possible redundant functions of these Rho GTPases in regulating platelet function. To investigate functional redundancies of RhoA and Rac1 in platelet production and function, mice with MK- and platelet-specific double- deficiencies in RhoA and Rac1 were generated. RhoA/Rac1 double-deficiency phenocopied the respective single knockouts without any additional effects in the double-knockout animals, demonstrating for the first time a functional non-redundancy of RhoA and Rac1 in platelet function. Antibodies against platelet glycoproteins (GP) trigger platelet destruction in immune thrombocytopenia (ITP) by binding to Fcγ receptors (FcγRs) on immune cells. However, antibodies against the platelet collagen receptor GPVI exert powerful anti-thrombotic action in vivo by inducing ectodomain shedding of the receptor associated with a transient thrombocytopenia. As shown in the final part of this thesis, blockade or deficiency of the inhibitory FcγRIIB abolished sequestration of anti-GPVI opsonized platelets in the hepatic vasculature and GPVI shedding. This process was mediated by liver sinusoidal endothelial cells (LSEC), the major FcγRIIB expressing cell type in the body. Furthermore, LSEC FcγRIIB mediated hepatic platelet sequestration and contributed to thrombocytopenia in mice treated with antibodies against αIIbβ3, the major target antigen in human ITP. These results reveal a novel and unexpected function of hepatic FcγRIIB in the processing of antibody-opsonized platelets.}, subject = {H{\"a}mostase}, language = {en} } @phdthesis{Schartner2018, author = {Schartner, Christoph}, title = {The regulation of corticotropin releasing hormone receptor 1 gene expression and its role in panic disorder}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150586}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Panic Disorder (PD) is characterized by unexpected, recurrent panic attacks, which are not restricted to certain situations, medication or stimuli. Like other anxiety disorders, PD is a multifactorial disorder and develops through the interaction of genetic and environmental risk factors. Despite an estimated heritability of up to 48\%, no distinct genetic mechanism could be revealed yet. A dysregulation of the stress response has been shown in patients with PD and several studies could find an association of components of the corticotropin-releasing factor (CRF) system with PD. The corticotropin releasing hormone receptor 1 (CRHR1) is the main receptor of CRF in the brain and thus a crucial regulator of cerebral CRF signaling. Recent genetic studies found an association of certain CRHR1 single nucleotide polymorphisms (SNPs) with PD and other anxiety disorders. Among the associated CRHR1 SNPs, rs17689918 showed further evidence in a multilevel study regulating CRHR1 gene expression in panic-relevant brain regions and affecting brain activation in fMRI experiments, as well as flight behavior in a behavioral avoidance task (Weber et al, 2015). Here, we aimed to investigate the underlying neurogenetic and neurobiological mechanisms, by which the rs17689918 risk allele affects CRHR1 gene expression and receptor function, and its putative function in the pathophysiology of PD. Due to its intronic position and the predicted change of splicing regulatory elements by the risk allele of rs17689918, the expression of alternative spliced CRHR1 isoforms was investigated using quantitative real-time PCR (qPCR) in a human post-mortem brain tissue sample. Of eight known CRHR1 isoforms, expression of three CRHR1 isoforms and the CRHR1-IT1-CRHR1 readthrough transcript variant 5 - all expressing the seven transmembrane domains needed for functional receptors - was analyzed. Subsequently, electrophysiological assays were developed to measure the receptor activity of differentially expressed CRHR1 isoforms via co-expressed Kir2.3 potassium channels in vitro. In a second approach, possible epigenetic regulation of CRHR1 expression by rs17689918 was investigated by analyses of DNA methylation patterns of a CpG Island within the CRHR1 promoter region, firstly in a case-control sample for PD and secondly in a healthy control sample, separated in high and low anxious individuals. To investigate a possible gene × epigene × environment interaction, the impact of early life stress by means of childhood trauma was evaluated via the childhood trauma questionnaire (CTQ). Finally, consequences of differential DNA methylation of the CRHR1 promoter region on gene expression were investigated by luciferase-based reporter gene assays in vitro. The expression of CRHR1β was significantly decreased in amygdalae and midbrains of risk allele carriers. The expression of CRHR1-IT1-CRHR1 readthrough transcript variant 5 was significantly increased in forebrains and midbrains of risk allele carriers. All other analyzed isoforms showed no differences in expression between non-risk and risk allele carriers of rs17689918. The electrophysiological recordings of membrane potential showed an activation of Kir2.3 channels by CRHR1β in contrast to an inconsistent mix of activation and inhibition of Kir2.3 by the main isoform CRHR1α. DNA methylation of the CRHR1 promoter region was significantly reduced in panic disorder patients, as well as in high anxious individuals of an independent healthy control sample, but no direct relation to the rs17689918 risk allele could be discerned. However, the combination of carrying the risk allele, low DNA methylation and high CTQ scores lead to increased sum scores in the Beck Anxiety Inventory (BAI) in healthy individuals. Functional analyses revealed an activation of gene expression by decreased DNA methylation of the promoter region in vitro. Our results revealed that rs17689918 regulates CRHR1 function by increasing the expression of alternative transcript variants with altered function. Our analyses of DNA methylation revealed decreased methylation as a new risk factor for panic disorder and high anxious behavior, which in combination with other risk factors like childhood trauma and the rs17689918 risk allele might further increase cognitive and somatic anxiety symptoms. This supports the role of CRHR1 as a plasticity gene of anxiety behavior, i.e. a gene that is highly regulated by epigenetic or post-transcriptional mechanisms in response to environmental stressors. By its role in CRF signaling, the dysregulation of CRHR1 might extensively affect the stress response and contribute to the pathophysiology of stress-related disorders like PD. The understanding of the underlying mechanisms, especially the genetic and epigenetic regulation, would however enhance CRHR1 as a target of improved future therapeutics for PD and other anxiety disorders.}, subject = {Corticoliberin}, language = {en} } @phdthesis{Confalonieri2018, author = {Confalonieri, Davide}, title = {Development and characterization of a bone marrow stem cell niche model}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163128}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Kritische Knochendefekte stellen heutzutage ein ungel{\"o}stes Problem in der klinischen Praxis dar, da die verf{\"u}gbaren prothetischen Optionen oft die mechanische Anpassung an das Gewebe nicht gew{\"a}hrleisten oder zu wichtigen immunologischen und Implantat-bedingten Komplikationen f{\"u}hren. In diesem Kontext erm{\"o}glichen Tissue Engineering-Ans{\"a}tze neue Strategien, um in vitro Zell-Material Interaktionen zu untersuchen und so die Implantatmaterialien zu optimieren. In dieser Arbeit habe ich Zell-Material Interaktionen eines neuen Kollagen-basierten Scaffolds untersucht, das langfristig als Tr{\"a}gerstruktur f{\"u}r eine zellbasierte Therapie f{\"u}r kritische Knochendefekte entwickelt werden soll. Im Rahmen der Dissertation konnte ich belegen, dass die Kollagen-basierten makropor{\"o}se Mikrocarrier f{\"u}r die Zellvermehrung humaner mesenchymaler Stammzellen (MSC) und deren osteogene Differenzierung unter GMP Bedingungen verwendet werden k{\"o}nnen. Außerdem habe ich die die Kokultur von h{\"a}matopoietischen Stammzellen des Knochenmarks und multiplen Myelomzellen funktionell charakterisiert. Ich konnte erstmals Kulturbedingungen etablieren, die die Langzeitkultur ohne die Verwendung von Zytokinen erm{\"o}glicht. Mittels dieser Kokultur konnte ich ein Knochenmarknischen-Modell etablieren und die Untersuchung der Expression von zentralen Signalkaskaden der Hom{\"o}ostase dieser Nische untersuchen. Ich konnte die Expression von zwei verschiedenen Isoformen von Osteopontin nachweisen, die in Tiermodellen nicht gefunden werden. Diese Isoformen des Osteopontins habe ich kloniert und die rekombinanten Isoformen exprimiert und ihre Rollen in der Hom{\"o}ostase der Knochenmarknische untersucht. Critical size bone defects represent nowadays an unresolved problem in the clinical practice, where the available prosthetic options often lack adequate mechanical matching to the host tissue or lead to important immunological and implant-related complications. In this context, Tissue Engineering approaches promise more effective strategies to study cell-material interactions in vitro and consequently optimize implant materials. In this work, I investigated the cell-scaffold interactions of a new collagen-based scaffold for a putative cell-based therapy for critical size defects to be developed. In the context of this thesis, I could demonstrate that the collagen-based macroporous microcarriers could be employed for the expansion and osteogenic differentiation of human mesenchymal stromal cells (MSCs) under GMP-compliant conditions. Moreover, I functionally characterized the co-culture of bone marrow hematopoietic stem cells and multiple myeloma cells. I was for the first time able to establish culture conditions allowing their long-term culture in absence of externally supplemented cytokines. Using this co-culture, I was able to establish a bone marrow niche model to investigate the expression of key signaling pathways involved in the niche´s homeostasis. I was able to demonstrate the expression of two different isoforms of Osteopontin, that could not previously be detected in animal models. Finally, I cloned these Osteopontin isoforms, expressed recombinant versions of the isoforms, and investigated their roles in the homeostasis of the bone marrow niche.}, subject = {bone marrow niche}, language = {en} } @phdthesis{Kleffel2018, author = {Kleffel, Sonja Beate}, title = {The role of cancer cell-expressed PD-1 in tumorigenesis and tumor immune evasion}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151205}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Melanoma and Merkel cell carcinoma (MCC) are highly aggressive cancers of the skin that frequently escape immune recognition and acquire resistance to chemotherapeutic agents, which poses a major obstacle to successful cancer treatment. Recently, a new class of therapeutics targeting the programmed cell death-1 (PD-1) immune checkpoint receptor has shown remarkable efficacy in the treatment of both cancers. Blockade of PD-1 on T cells activates cancer-specific immune responses that can mediate tumor regression. The data presented in this Ph.D. thesis demonstrates that PD-1 is also expressed by subsets of cancer cells in melanoma and MCC. Moreover, this work identifies PD-1 as a novel tumor cell-intrinsic growth receptor, even in the absence of T cell immunity. PD-1 is expressed by tumorigenic cell subsets in melanoma patient samples and established human and murine cell lines that also co-express ABCB5, a marker of immunoregulatory tumor- initiating cells in melanoma. Consistently, melanoma-expressed PD-1 downmodulates T effector cell functions and increases the intratumoral frequency of tolerogenic myeloid- derived suppressor cells. PD-1 inhibition on melanoma cells by RNA interference, blocking antibodies, or mutagenesis of melanoma-PD-1 signaling motifs suppresses tumor growth in immunocompetent, immunocompromised, and PD-1-deficient tumor graft recipient mice. Conversely, melanoma-specific PD-1 overexpression enhances tumorigenicity, including in mice lacking adaptive immunity. Engagement of melanoma- PD-1 by its ligand PD-L1 promotes tumor growth, whereas melanoma-PD-L1 inhibition or knockout of host-PD-L1 attenuates growth of PD-1-positive melanomas. Mechanistically, the melanoma-PD-1 receptor activates mTOR signaling mediators, including ribosomal protein S6. In a proof-of-concept study, tumoral expression of phospho-S6 in pretreatment tumor biopsies correlated with clinical responses to anti-PD-1 therapy in melanoma patients. In MCC, PD-1 is similarly co-expressed by ABCB5+ cancer cell subsets in clinical tumor specimens and established human cell lines. ABCB5 renders MCC cells resistant to the standard-of-care chemotherapeutic agents, carboplatin and etoposide. Antibody-mediated ABCB5 blockade reverses chemotherapy resistance and inhibits tumor xenograft growth by enhancing chemotherapy-induced tumor cell killing. Furthermore, engagement of MCC-expressed PD-1 by its ligands, PD-L1 and PD-L2, promotes proliferation and activates MCC-intrinsic mTOR signaling. Consistently, antibody- mediated PD-1 blockade inhibits MCC tumor xenograft growth and phosphorylation of mTOR effectors in immunocompromised mice. In summary, these findings identify cancer cell-intrinsic functions of the PD-1 pathway in tumorigenesis and suggest that blocking melanoma- and MCC-expressed PD-1 might contribute to the striking clinical efficacy of anti-PD-1 therapy. Additionally, these results establish ABCB5 as a previously unrecognized chemoresistance mechanism in MCC.}, subject = {Melanom}, language = {en} } @phdthesis{Slawig2018, author = {Slawig, Anne}, title = {Reconstruction methods for the frequency-modulated balanced steady-state free precession MRI-sequence}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162871}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {This work considered the frequency-modulated balanced steady-state free precession (fm-bSSFP) sequence as a tool to provide banding free bSSFP MR images. The sequence was implemented and successfully applied to suppress bandings in various in vitro and in vivo examples. In combination with a radial trajectory it is a promising alternative for standard bSSFP applications. First, two specialized applications were shown to establish the benefits of the acquisition strategy in itself. In real time cardiac imaging, it was shown that the continuous shift in frequency causes a movement of the bandings across the FOV. Thus, no anatomical region is constantly impaired, and a suitable timeframe can be found to examine all important structures. Furthermore, a combination of images with different artifact positions, similar to phase-cycled acquisitions is possible. In this way, fast, banding-free imaging of the moving heart was realized. Second, acquisitions with long TR were shown. While standard bSSFP suffers from increasing incidence of bandings with higher TR values, the frequency-modulated approach provided banding free images, regardless of the TR. A huge disadvantage of fm-bSSFP, in combination with the radial trajectory, is the decrease in signal intensity. In this work a specialized reconstruction method, the multifrequency reconstruction for frequency-modulated bSSFP (Muffm), was established, which successfully compensated that phenomena. The application of Muffm to several anatomical sites, such as inner ear, legs and cardiac acquisitions, proofed the advantageous SNR of the reconstruction. Furthermore, fm-bSSFP was applied to the clinically highly relevant task of water-fat separation. Former approaches of a phase-sensitive separation procedure in combination with standard bSSFP showed promising results but failed in cases of high inhomogeneity or high field strengths where banding artifacts become a major issue. The novel approach of using the fm-bSSFP acquisition strategy with the separation approach provided robust, reliable images of high quality. Again, losses in signal intensity could be regained by Muffm, as both approaches are completely compatible. Opposed to conventional banding suppression techniques, like frequency-scouts or phase-cycling, all reconstruction methods established in this work rely on a single radial acquisition, with scan times similar to standard bSSFP scans. No prolonged measurement times occur and patient time in the scanner is kept as short as possible, improving patient comfort, susceptibility to motion or physiological noise and cost of one scan. All in all, the frequency-modulated acquisition in combination with specializes reconstruction methods, leads to a completely new quality of images with short acquisition times.}, subject = {Kernspintomografie}, language = {en} } @phdthesis{Wiedenmann2018, author = {Wiedenmann, Jonas}, title = {Induced topological superconductivity in HgTe based nanostructures}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162782}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {This thesis describes the studies of topological superconductivity, which is predicted to emerge when pair correlations are induced into the surface states of 2D and 3D topolog- ical insulators (TIs). In this regard, experiments have been designed to investigate the theoretical ideas first pioneered by Fu and Kane that in such system Majorana bound states occur at vortices or edges of the system [Phys. Rev. Lett. 100, 096407 (2008), Phys. Rev. B 79, 161408 (2009)]. These states are of great interest as they constitute a new quasiparticle which is its own antiparticle and can be used as building blocks for fault tolerant topological quantum computing. After an introduction in chapter 1, chapter 2 of the thesis lays the foundation for the understanding of the field of topology in the context of condensed matter physics with a focus on topological band insulators and topological superconductors. Starting from a Chern insulator, the concepts of topological band theory and the bulk boundary corre- spondence are explained. It is then shown that the low energy Hamiltonian of mercury telluride (HgTe) quantum wells of an appropriate thickness can be written as two time reversal symmetric copies of a Chern insulator. This leads to the quantum spin Hall effect. In such a system, spin-polarized one dimensional conducting states form at the edges of the material, while the bulk is insulating. This concept is extended to 3D topological insulators with conducting 2D surface states. As a preliminary step to treating topological superconductivity, a short review of the microscopic theory of superconductivity, i.e. the theory of Bardeen, Cooper, and Shrieffer (BCS theory) is presented. The presence of Majorana end modes in a one dimensional superconducting chain is explained using the Kitaev model. Finally, topological band insulators and conventional superconductivity are combined to effectively engineer p-wave superconductivity. One way to investigate these states is by measuring the periodicity of the phase of the Josephson supercurrent in a topological Josephson junction. The signature is a 4π-periodicity compared to the 2π-periodicity in conventional Josephson junctions. The proof of the presence of this effect in HgTe based Josephson junction is the main goal of this thesis and is discussed in chapters 3 to 6. Chapter 3 describes in detail the transport of a 3D topological insulator based weak link under radio-frequency radiation. The chapter starts with a review of the state of research of (i) strained HgTe as 3D topological insulator and (ii) the progress of induc- ing superconducting correlations into the topological surface states and the theoretical predictions of 3D TI based Josephson junctions. Josephson junctions based on strained HgTe are successfully fabricated. Before studying the ac driven Josephson junctions, the dc transport of the devices is analysed. The critical current as a function of temperature is measured and it is possible to determine the induced superconducting gap. Under rf illumination Shapiro steps form in the current voltage characteristic. A missing first step at low frequencies and low powers is found in our devices. This is a signature of a 4π-periodic supercurrent. By studying the device in a wide parameter range - as a 147148 SUMMARY function of frequency, power, device geometry and magnetic field - it is shown that the results are in agreement with the presence of a single gapless Andreev doublet and several conventional modes. Chapter 4 gives results of the numerical modelling of the I -V dynamics in a Josephson junction where both a 2π- and a 4π-periodic supercurrents are present. This is done in the framework of an equivalent circuit representation, namely the resistively shunted Josephson junction model (RSJ-model). The numerical modelling is in agreement with the experimental results in chapter 3. First, the missing of odd Shapiro steps can be understood by a small 4π-periodic supercurrent contribution and a large number of modes which have a conventional 2π-periodicity. Second, the missing of odd Shapiro steps occurs at low frequency and low rf power. Third, it is shown that stochastic processes like Landau Zener tunnelling are most probably not responsible for the 4π contribution. In a next step the periodicity of Josephson junctions based on quantum spin Hall insulators using are investigated in chapter 5. A fabrication process of Josephson junctions based on inverted HgTe quantum wells was successfully developed. In order to achieve a good proximity effect the barrier material was removed and the superconductor deposited without exposing the structure to air. In a next step a gate electrode was fabricated which allows the chemical potential of the quantum well to be tuned. The measurement of the diffraction pattern of the critical current Ic due to a magnetic field applied perpendicular to the sample plane was conducted. In the vicinity to the expected quantum spin Hall phase, the pattern resembles that of a superconducting quantum interference device (SQUID). This shows that the current flows predominantly on the edges of the mesa. This observation is taken as a proof of the presence of edge currents. By irradiating the sample with rf, missing odd Shapiro steps up to step index n = 9 have been observed. This evidences the presence of a 4π-periodic contribution to the supercurrent. The experiment is repeated using a weak link based on a non-inverted HgTe quantum well. This material is expected to be a normal band insulator without helical edge channels. In this device, all the expected Shapiro steps are observed even at low frequencies and over the whole gate voltage range. This shows that the observed phenomena are directly connected to the topological band structure. Both features, namely the missing of odd Shapiro steps and the SQUID like diffraction pattern, appear strongest towards the quantum spin Hall regime, and thus provide evidence for induced topological superconductivity in the helical edge states. A more direct way to probe the periodicity of the Josephson supercurrent than using Shapiro steps is the measurement of the emitted radiation of a weak link. This experiment is presented in chapter 6. A conventional Josephson junction converts a dc bias V to an ac current with a characteristic Josephson frequency fJ = eV /h. In a topological Josephson junction a frequency at half the Josephson frequency fJ /2 is expected. A new measurement setup was developed in order to measure the emitted spectrum of a single Josephson junction. With this setup the spectrum of a HgTe quantum well based Josephson junction was measured and the emission at half the Josephson frequency fJ /2 was detected. In addition, fJ emission is also detected depending on the gate voltage and detection frequency. The spectrum is again dominated by half the Josephson emission at low voltages while the conventional emission is determines the spectrum at high voltages. A non-inverted quantum well shows only conventional emission over the whole gateSUMMARY 149 voltage and frequency range. The linewidth of the detected frequencies gives a measure on the lifetime of the bound states: From there, a coherence time of 0.3-4ns for the fJ /2 line has been deduced. This is generally shorter than for the fJ line (3-4ns). The last part of the thesis, chapter 7, reports on the induced superconducting state in a strained HgTe layer investigated by point-contact Andreev reflection spectroscopy. For the experiment, a HgTe mesa was fabricated with a small constriction. The diameter of the orifice was chosen to be smaller than the mean free path estimated from magne- totransport measurements. Thus one gets a ballistic point-contact which allows energy resolved spectroscopy. One part of the mesa is covered with a superconductor which induces superconducting correlations into the surface states of the topological insulator. This experiment therefore probes a single superconductor normal interface. In contrast to the Josephson junctions studied previously, the geometry allows the acquisition of energy resolved information of the induced superconducting state through the measurement of the differential conductance dI/dV as a function of applied dc bias for various gate voltages, temperatures and magnetic fields. An induced superconducting order parame- ter of about 70µeV was extracted but also signatures of the niobium gap at the expected value around Δ Nb ≈ 1.1meV have been found. Simulations using the theory developed by Blonder, Tinkham and Klapwijk and an extended model taking the topological surface states into account were used to fit the data. The simulations are in agreement with a small barrier at the topological insulator-induced topological superconductor interface and a high barrier at the Nb to topological insulator interface. To understand the full con- ductance curve as a function of applied voltage, a non-equilibrium driven transformation is suggested. The induced superconductivity is suppressed at a certain bias value due to local electron population. In accordance with this suppression, the relevant scattering regions change spatially as a function of applied bias. To conclude, it is emphasized that the experiments conducted in this thesis found clear signatures of induced topological superconductivity in HgTe based quantum well and bulk devices and opens up the avenue to many experiments. It would be interesting to apply the developed concepts to other topological matter-superconductor hybrid systems. The direct spectroscopy and manipulation of the Andreev bound states using circuit quantum electrodynamic techniques should be the next steps for HgTe based samples. This was already achieved in superconducting atomic break junctions by the group in Saclay [Science 2015, 349, 1199-1202 (2015)]. Another possible development would be the on-chip detection of the emitted spectrum as a function of the phase φ through the junction. In this connection, the topological junction needs to be shunted by a parallel ancillary junction. Such a setup would allow the current phase relation I(φ) directly and the lifetime of the bound states to be measured directly. By coupling this system to a spectrometer, which can be another Josephson junction, the energy dependence of the Andreev bound states E(φ) could be obtained. The experiments on the Andreev reflection spectroscopy described in this thesis could easily be extended to two dimensional topological insulators and to more complex geometries, like a phase bias loop or a tunable barrier at the point-contact. This work might also be useful for answering the question how and why Majorana bound states can be localized in quantum spin Hall systems.}, subject = {Quecksilbertellurid}, language = {en} } @phdthesis{Zenk2018, author = {Zenk, Markus}, title = {On Numerical Methods for Astrophysical Applications}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162669}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Diese Arbeit befasst sich mit der Approximation der L{\"o}sungen von Modellen zur Beschreibung des Str{\"o}mungsverhaltens in Atmosph{\"a}ren. Im Speziellen umfassen die hier behandelten Modelle die kompressiblen Euler Gleichungen der Gasdynamik mit einem Quellterm bez{\"u}glich der Gravitation und die Flachwassergleichungen mit einem nicht konstanten Bodenprofil. Verschiedene Methoden wurden bereits entwickelt um die L{\"o}sungen dieser Gleichungen zu approximieren. Im Speziellen geht diese Arbeit auf die Approximation von L{\"o}sungen nahe des Gleichgewichts und, im Falle der Euler Gleichungen, bei kleinen Mach Zahlen ein. Die meisten numerischen Methoden haben die Eigenschaft, dass die Qualit{\"a}t der Approximation sich mit der Anzahl der Freiheitsgrade verbessert. In der Praxis werden deswegen diese numerischen Methoden auf großen Computern implementiert um eine m{\"o}glichst hohe Approximationsg{\"u}te zu erreichen. Jedoch sind auch manchmal diese großen Maschinen nicht ausreichend, um die gew{\"u}nschte Qualit{\"a}t zu erreichen. Das Hauptaugenmerk dieser Arbeit ist darauf gerichtet, die Qualit{\"a}t der Approximation bei gleicher Anzahl von Freiheitsgrade zu verbessern. Diese Arbeit ist im Zusammenhang einer Kollaboration zwischen Prof. Klingenberg des Mathemaitschen Instituts in W{\"u}rzburg und Prof. R{\"o}pke des Astrophysikalischen Instituts in W{\"u}rzburg entstanden. Das Ziel dieser Kollaboration ist es, Methoden zur Berechnung von stellarer Atmosph{\"a}ren zu entwickeln. In dieser Arbeit werden vor allem zwei Problemstellungen behandelt. Die erste Problemstellung bezieht sich auf die akkurate Approximation des Quellterms, was zu den so genannten well-balanced Schemata f{\"u}hrt. Diese erlauben genaue Approximationen von L{\"o}sungen nahe des Gleichgewichts. Die zweite Problemstellung bezieht sich auf die Approximation von Str{\"o}mungen bei kleinen Mach Zahlen. Es ist bekannt, dass L{\"o}sungen der kompressiblen Euler Gleichungen zu L{\"o}sungen der inkompressiblen Euler Gleichungen konvergieren, wenn die Mach Zahl gegen null geht. Klassische numerische Schemata zeigen ein stark diffusives Verhalten bei kleinen Mach Zahlen. Das hier entwickelte Schema f{\"a}llt in die Kategorie der asymptotic preserving Schematas, d.h. das numerische Schema ist auf einem diskrete Level kompatibel mit dem auf dem Kontinuum gezeigten verhalten. Zus{\"a}tzlich wird gezeigt, dass die Diffusion des hier entwickelten Schemas unabh{\"a}ngig von der Mach Zahl ist. In Kapitel 3 wird ein HLL approximativer Riemann L{\"o}ser f{\"u}r die Approximation der L{\"o}sungen der Flachwassergleichungen mit einem nicht konstanten Bodenprofil angewendet und ein well-balanced Schema entwickelt. Die meisten well-balanced Schemata f{\"u}r die Flachwassergleichungen behandeln nur den Fall eines Fluids im Ruhezustand, die so genannten Lake at Rest L{\"o}sungen. Hier wird ein Schema entwickelt, welches sich mit allen Gleichgewichten befasst. Zudem wird eine zweiter Ordnung Methode entwickelt, welche im Gegensatz zu anderen in der Literatur nicht auf einem iterativen Verfahren basiert. Numerische Experimente werden durchgef{\"u}hrt um die Vorteile des neuen Verfahrens zu zeigen. In Kapitel 4 wird ein Suliciu Relaxations L{\"o}ser angepasst um die hydrostatischen Gleichgewichte der Euler Gleichungen mit einem Gravitationspotential aufzul{\"o}sen. Die Gleichungen der hydrostatischen Gleichgewichte sind unterbestimmt und lassen deshalb keine Eindeutigen L{\"o}sungen zu. Es wird jedoch gezeigt, dass das neue Schema f{\"u}r eine große Klasse dieser L{\"o}sungen die well-balanced Eigenschaft besitzt. F{\"u}r bestimmte Klassen werden Quadraturformeln zur Approximation des Quellterms entwickelt. Es wird auch gezeigt, dass das Schema robust, d.h. es erh{\"a}lt die Positivit{\"a}t der Masse und Energie, und stabil bez{\"u}glich der Entropieungleichung ist. Die numerischen Experimente konzentrieren sich vor allem auf den Einfluss der Quadraturformeln auf die well-balanced Eigenschaften. In Kapitel 5 wird ein Suliciu Relaxations Schema angepasst f{\"u}r Simulationen im Bereich kleiner Mach Zahlen. Es wird gezeigt, dass das neue Schema asymptotic preserving und die Diffusion kontrolliert ist. Zudem wird gezeigt, dass das Schema f{\"u}r bestimmte Parameter robust ist. Eine Stabilit{\"a}t wird aus einer Chapman-Enskog Analyse abgeleitet. Resultate numerische Experimente werden gezeigt um die Vorteile des neuen Verfahrens zu zeigen. In Kapitel 6 werden die Schemata aus den Kapiteln 4 und 5 kombiniert um das Verhalten des numerischen Schemas bei Fl{\"u}ssen mit kleiner Mach Zahl in durch die Gravitation geschichteten Atmosph{\"a}ren zu untersuchen. Es wird gezeigt, dass das Schema well-balanced ist. Die Robustheit und die Stabilit{\"a}t werden analog zu Kapitel 5 behandelt. Auch hier werden numerische Tests durchgef{\"u}hrt. Es zeigt sich, dass das neu entwickelte Schema in der Lage ist, die Dynamiken besser Aufzul{\"o}sen als vor der Anpassung. Das Kapitel 7 besch{\"a}ftigt sich mit der Entwicklung eines multidimensionalen Schemas basierend auf der Suliciu Relaxation. Jedoch ist die Arbeit an diesem Ansatz noch nicht beendet und numerische Resultate k{\"o}nnen nicht pr{\"a}sentiert werden. Es wird aufgezeigt, wo sich die Schw{\"a}chen dieses Ansatzes befinden und weiterer Entwicklungsbedarf besteht.}, subject = {Str{\"o}mung}, language = {en} } @phdthesis{Wannagat2018, author = {Wannagat, Wienke Charlotte}, title = {Cognitive Processes of Discourse Comprehension in Children and Adults - Comparisons between Written, Auditory, and Audiovisual Modes of Presentation -}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162515}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {In drei Studien wurde untersucht, wie sich unterschiedliche Darbietungsformate (schriftlich, auditiv, audiovisuell (auditiv + Bilder) auf das Verst{\"a}ndnis semantisch identischer Inhalte auswirken. Dabei interessierte insbesondere der Entwicklungsverlauf von der ersten Klasse bis zum Erwachsenenalter. Dass sich Bilder f{\"o}rderlich auf die Verst{\"a}ndnisleistung auswirken k{\"o}nnen, gilt als gut untersucht (z.B. Carney \& Levin, 2002). Anders als viele bisherige Studien erfassen wir Textverstehen mit impliziten Maßen, die differenziertere R{\"u}ckschl{\"u}sse auf die, g{\"a}ngigen Theorien zufolge, zugrundeliegenden Prozesse zulassen: Textverstehen geht mit der Konstruktion von drei Ebenen mentaler Repr{\"a}sentationen einher (vgl. Kintsch, 1998). Weiterhin bedeutet erfolgreiches Textverstehen, eine auf lokaler und globaler Ebene koh{\"a}rente mentale Repr{\"a}sentation zu konstruieren (z.B. Schnotz \& Dutke, 2004). Mit einem Satz-Rekognitionstest (vgl. Schmalhofer \& Glavanov, 1986) untersuchten wir, ob sich das Ged{\"a}chtnis f{\"u}r die Textoberfl{\"a}che, die Textbasis und das Situationsmodell bei 103 8- und 10-J{\"a}hrigen zwischen schriftlicher, auditiver und audiovisueller (Studie 1) und bei 106 7-, 9- und 11-J{\"a}hrigen zwischen auditiver und audiovisueller Darbietung narrativer Texte (Studie 2) unterscheidet. Weiterhin (Studie 3) untersuchten wir mit 155 9- und 11-J{\"a}hrigen, inwieweit sich die F{\"a}higkeit der Inferenzbildung zur Herstellung lokaler und globaler Koh{\"a}renz zwischen schriftlicher, auditiver und audiovisueller Darbietung unterscheidet. Als Indikator dienten die Reaktionszeiten auf W{\"o}rter, die mit einem {\"u}ber (global)- oder untergeordneten (lokal) Protagonistenziel assoziiert sind. Insgesamt zeigte sich, dass Sch{\"u}ler bis zu einem Alter von 11 Jahren nicht nur die Textoberfl{\"a}che besser erinnern, sondern auch besser in der Lage sind ein Situationsmodell zu konstruieren, wenn einem Text Bilder beigef{\"u}gt sind. Dies zeigte sich sowohl im Vergleich mit auditiver als auch mit schriftlicher Darbietung. Bei Erwachsenen zeigte sich kein Effekt der Darbietungsform. Sowohl 9- als auch 11-J{\"a}hrigen gelingt außerdem die Herstellung globaler Koh{\"a}renz bei audiovisueller Darbietung besser als bei auditiver. Die schriftliche Darbietung zeigte sich im Vergleich zur auditiven sowohl im Hinblick auf lokale als auch auf globale Koh{\"a}renz {\"u}berlegen.}, subject = {Textverstehen}, language = {en} } @phdthesis{Namal2018, author = {Namal, Imge}, title = {Fabrication and Optical and Electronic Characterization of Conjugated Polymer-Stabilized Semiconducting Single-Wall Carbon Nanotubes in Dispersions and Thin Films}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162393}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {In order to shrink the size of semiconductor devices and improve their efficiency at the same time, silicon-based semiconductor devices have been engineered, until the material almost reaches its performance limits. As the candidate to be used next in semiconducting devices, single-wall carbon nanotubes show a great potential due to their promise of increased device efficiency and their high charge carrier mobilities in the nanometer size active areas. However, there are material based problems to overcome in order to imply SWNTs in the semiconductor devices. SWNTs tend to aggregate in bundles and it is not trivial to obtain an electronically or chirally homogeneous SWNT dispersion and when it is done, a homogeneous thin film needs to be produced with a technique that is practical, easy and scalable. This work was aimed to solve both of these problems. In the first part of this study, six different polymers, containing fluorene or carbazole as the rigid part and bipyridine, bithiophene or biphenyl as the accompanying copolymer unit, were used to selectively disperse semiconducting SWNTs. With the data obtained from absorption and photoluminescence spectroscopy of the corresponding dispersions, it was found out that the rigid part of the copolymer plays a primary role in determining its dispersion efficiency and electronic sorting ability. Within the two tested units, carbazole has a higher π electron density. Due to increased π-π interactions, carbazole containing copolymers have higher dispersion efficiency. However, the electronic sorting ability of fluorene containing polymers is superior. Chiral selection of the polymers in the dispersion is not directly foreseeable from the selection of backbone units. At the end, obtaining a monochiral dispersion is found to be highly dependent on the used raw material in combination to the preferred polymer. Next, one of the best performing polymers due to high chirality enrichment and electronic sorting ability was chosen in order to disperse SWNTs. Thin films of varying thickness between 18 ± 5 to 755o±o5 nm were prepared using vacuum filtration wet transfer method in order to analyze them optically and electronically. The scalability and efficiency of the integrated thin film production method were shown using optical, topographical and electronic measurements. The relative photoluminescence quantum yield of the radiative decay from the SWNT thin films was found to be constant for the thickness scale. Constant roughness on the film surface and linearly increasing concentration of SWNTs were also supporting the scalability of this thin film production method. Electronic measurements on bottom gate top contact transistors have shown an increasing charge carrier mobility for linear and saturation regimes. This was caused by the missing normalization of the mobility for the thickness of the active layer. This emphasizes the importance of considering this dimension for comparison of different field effect transistor mobilities.}, subject = {Feldeffekttransistor}, language = {en} }