@misc{Gamaleldin2021,
  type      = {Master Thesis},
  author    = {Gamaleldin, Mariam},
  title     = {Non-canonical Signaling of μ-opioid Receptors},
  doi       = {10.25972/OPUS-24032},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240327},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {According to the "canonical" paradigm of GPCR signaling, agonist-bound GPCRs only signal to the downstream adenylyl cyclase enzyme when they are seated at the plasma membrane. Upon prolonged binding of an agonist, receptor internalization usually takes place, leading to the termination of this downstream signaling pathway and activation of alternative ones. However, a set of recent studies have shown that at least some GPCRs (e.g. thyroid stimulating hormone receptor) continue signaling to adenylyl cyclase after internalization. In this study, I aimed to investigate canonical signaling by internalized μ opioid receptors (MORs), which are Gi-coupled receptors, using a fluorescence resonance energy transfer (FRET) sensor for cyclic AMP (cAMP) known as Epac1-camps. My results show that the cyclic AMP inhibition signal induced by the binding of DAMGO, a MOR agonist, persists after agonist washout. We hypothesized that this persistent signal might come from internalized DAMGO-bound receptors located in the endosomal compartment. To test this hypothesis, I used dynasore and Dyngo 4a, two dynamin inhibitors that are known to prevent clathrin-mediated endocytosis. Interestingly, dynasore but not Dyngo 4a pretreatment largely blunted the response to MOR activation as well as to adenylyl cyclase activation with Forskolin (FSK). In addition, DAMGO-induced cAMP signal remained persistent even in the presence of 30 M Dyngo 4a. These results might point to a complex interplay between clathrin-mediated internalization and MOR signaling. Further experiments are required to elucidate the mechanisms underlying the persistent MOR signaling and to fully clarify whether MORs are capable of Gi signaling in the endosomal compartment.},
  language  = {en}
}
@phdthesis{Baier2018,
  author    = {Baier, Pablo A.},
  title     = {Simulator for Minimally Invasive Vascular Interventions: Hardware and Software},
  isbn      = {978-3-945459-22-5},
  doi       = {10.25972/OPUS-16119},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161190},
  school      = {Universit{\"a}t W{\"u}rzburg},
  pages     = {118},
  year      = {2018},
  abstract  = {A complete simulation system is proposed that can be used as an educational tool by physicians in training basic skills of Minimally Invasive Vascular Interventions. In the first part, a surface model is developed to assemble arteries having a planar segmentation. It is based on Sweep Surfaces and can be extended to T- and Y-like bifurcations. A continuous force vector field is described, representing the interaction between the catheter and the surface. The computation time of the force field is almost unaffected when the resolution of the artery is increased. The mechanical properties of arteries play an essential role in the study of the circulatory system dynamics, which has been becoming increasingly important in the treatment of cardiovascular diseases. In Virtual Reality Simulators, it is crucial to have a tissue model that responds in real time. In this work, the arteries are discretized by a two dimensional mesh and the nodes are connected by three kinds of linear springs. Three tissue layers (Intima, Media, Adventitia) are considered and, starting from the stretch-energy density, some of the elasticity tensor components are calculated. The physical model linearizes and homogenizes the material response, but it still contemplates the geometric nonlinearity. In general, if the arterial stretch varies by 1\% or less, then the agreement between the linear and nonlinear models is trustworthy. In the last part, the physical model of the wire proposed by Konings is improved. As a result, a simpler and more stable method is obtained to calculate the equilibrium configuration of the wire. In addition, a geometrical method is developed to perform relaxations. It is particularly useful when the wire is hindered in the physical method because of the boundary conditions. The physical and the geometrical methods are merged, resulting in efficient relaxations. Tests show that the shape of the virtual wire agrees with the experiment. The proposed algorithm allows real-time executions and the hardware to assemble the simulator has a low cost.},
  subject      = {Computersimulation},
  language  = {en}
}
@phdthesis{Bolze2018,
  author    = {Bolze, Tom},
  title     = {Photodynamics of a fluorescent tetrazolium salt and shaping of femtosecond Laguerre-Gaussian laser modes in time and space},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-160902},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {This thesis will outline studies performed on the fluorescence dynamics of phenyl-benzo- [c]-tetrazolo-cinnolium chloride (PTC) in alcoholic solutions with varying viscosity using time-resolved fluoro-spectroscopic methods. Furthermore, the properties of femtosecond Laguerre-Gaussian (LG) laser pulses will be investigated with respect to their temporal and spatial features and an approach will be developed to measure and control the spatial intensity distribution on the time scale of the pulse. Tetrazolium salts are widely used in biological assays for their low oxidation and reduction thresholds and spectroscopic properties. However, a neglected feature in these applications is the advantage that detection of emitted light has over the determination of the absorbance. To corroborate this, PTC as one of the few known fluorescent tetrazolium salts was investigated with regard to its luminescent features. Steady-state spectroscopy revealed how PTC can be formed by a photoreaction from 2,3,5-triphenyl-tetrazolium chloride (TTC) and how the fluorescence quantum yield behaved in alcoholic solvents with different viscosity. In the same array of solvents time correlated single photon counting (TCSPC) measurements were performed and the fluorescence decay was investigated. Global analysis of the results revealed different dynamics in the different solvents, but although the main emission constant did change with the solvent, taking the fluorescence quantum yield into consideration resulted in an independence of the radiative rate from the solvent. The non-radiative rate, however, was highly solvent dependent and responsible for the observed solvent-related changes in the fluorescence dynamics. Further studies with the increased time resolution of femtosecond fluorescence upconversion revealed an independence of the main emission constant from the excitation energy, however the dynamics of the cooling processes prior to emission were prolonged for higher excitation energy. This led to a conceivable photoreaction scheme with one emissive state with a competing non-radiative relaxation channel, that may involve an intermediate state. LG laser beams and their properties have seen a lot of scientific attention over the past two decades. Also in the context of new techniques pushing the limit of technology further to explore new phenomena, it is essential to understand the features of this beam class and check the consistency of the findings with theoretical knowledge. The mode conversion of a Hermite-Gaussian (HG) mode into a LG mode with the help of a spiral phase plate (SPP) was investigated with respect to its space-time characteristics. It was found that femtosecond LG and HG pulses of a given temporal duration share the same spectrum and can be characterized using the same well-established methods. The mode conversion proved to only produce the desired LG mode with its characteristic orbital angular momentum (OAM), that is conserved after frequency doubling the pulse. Furthermore, it was demonstrated that temporal shaping of the HG pulse does not alter the result of its mode-conversion, as three completely different temporal pulse shapes produced the same LG mode. Further attention was given to the sum frequency generation of fs LG beams and dynamics of the interference of a HG and a LG pulse. It was found that if both are chirped with inverse signs the spatial intensity distribution does rotate around the beam axis on the time scale of the pulse. A strategy was found that would enable a measurement of these dynamics by upconversion of the interference with a third gate pulse. The results of which are discussed theoretically and an approach of an experimental realization had been made. The simulated findings had only been reproduced to a limited extend due to experimental limitations, especially the interferometric stability of the setup.},
  subject      = {Tetrazoliumsalze},
  language  = {en}
}
@phdthesis{Bittorf2021,
  author    = {Bittorf, Patrick},
  title     = {Entwicklung, Herstellung und pr{\"a}klinisches Studienprogramm f{\"u}r ein Arzneimittel f{\"u}r neuartige Therapien zur Behandlung der schweren Form der H{\"a}mophilie A},
  doi       = {10.25972/OPUS-23185},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231858},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Bevor ein zellbasiertes GTMP erstmalig beim Menschen angewendet werden kann, m{\"u}ssen verschiedene notwendige nicht-klinische Studien durchgef{\"u}hrt werden. Wichtig ist hier u.a. die Untersuchung der Biodistribution im Tiermodel. Diese umfasst die Verteilung, das Engraftment, die Persistenz, die Eliminierung und gegebenenfalls die Expansion der humanen Zellen in verschiedenen Organen, meistens im Mausmodel. Deshalb wurde eine qPCR-basierte Analysenmethode entwickelt, mit der humane genomische DNA innerhalb von muriner genomischer DNA bestimmt werden kann, und entsprechend den regulatorischen Richtlinien der European Medicines Agency und des International Council for Harmonisation validiert. Anschließend wurde diese Methode innerhalb einer pr{\"a}klinischen worst-case Szenario Biodistributionsstudie angewendet. Das Ziel dieser Studie war die Untersuchung des Biodistributionsprofils von genetisch modifizierten Blood Outgrowth Endothelial Cells von H{\"a}mophilie A Patienten 24 Stunden und sieben Tage nach intraven{\"o}ser Applikation einer Dosis von 2x106 Zellen. Die Isolation, genetische Modifikation und die Expansion der Zellen sollte entsprechend den Richtlinien der Guten Herstellungspraxis durchgef{\"u}hrt werden. Hierbei ist die Auswahl und Anwendung geeigneter und essentieller Rohstoffe wichtig. Gleichermaßen ist die Durchf{\"u}hrung einer definierten Qualit{\"a}tskontrollstrategie notwendig und die Patientenzellen sollten nur innerhalb von nicht-klinischen Studien eingesetzt werden, wenn alle Akzeptanzkriterien erf{\"u}llt wurden. Die Validierung der qPCR-Methode zeigte eine hohe Genauigkeit, Pr{\"a}zision und Linearit{\"a}t innerhalb des Konzentrationsintervalls von 1:1x103 bis 1:1x106 humanen zu murinen Genomen. Bei Anwendung dieser Methode f{\"u}r die Biodistributionsstudie konnten nach 24 Stunden humane Genome in vier der acht untersuchten Mausorgane bestimmt werden. Nach sieben Tagen konnten in keinem der acht Organe humane Genome nachgewiesen werden...},
  subject      = {Arzneimittel},
  language  = {de}
}
@phdthesis{Upcin2022,
  author    = {Upcin, Berin},
  title     = {Contribution of vascular adventitia-resident progenitor cells to new vessel formation in \(ex\) \(vivo\) 3D models},
  doi       = {10.25972/OPUS-25507},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255070},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Ongoing research to fight cancer, one of the dominant diseases of the 21st century has led to big progress especially when it comes to understanding the tumor growth and metastasis. This includes the discovery of the molecular mechanisms of tumor vascularization, which is critically required for establishment of tumor metastasis. Formation of new blood vessels is the first step in tumor vascularization. Therefore, understanding the molecular and cellular basis of tumor vascularization attracted a significant effort studying in biomedical research. The blood vessels for supplying tumor can be formed by sprouting from pre-existing vessels, a process called angiogenesis, or by vasculogenesis, that is de novo formation of blood vessels from not fully differentiated progenitor cell populations. Vasculogenic endothelial progenitor cells (EPCs) can either be activated from populations in the bone marrow reaching the pathological region via the circulation or they can be recruited from local reservoirs. Neovessel formation influences tumor progression, hence therapeutic response model systems of angiogenesis/vasculogenesis are necessary to study the underlying mechanisms. Although, initially the research in this area focused more on angiogenesis, it is now well understood that both angiogenesis and postnatal vasculogenesis contribute to neovessel formation in adult under both most pathological as well as physiological conditions. Studies in the last two decades demonstrate that in addition to the intimal layer of fully differentiated mature endothelial cells (ECs) and various smaller supplying vessels (vasa vasorum) that can serve as a source for new vessels by angiogenesis, especially the adventitia of large and medium size blood vessels harbors various vascular wall-resident stem and progenitor cells (VW-SPCs) populations that serve as a source for new vessels by postnatal vasculogenesis. However, little is known about the potential role of VW-SPCs in tumor vascularization. To this end, the present work started first to establish a modified aortic ring assay (ARA) using mouse aorta in order to study the contribution of vascular adventitia-resident VW-SPCs to neovascularization in general and in presence of tumor cells. ARA is already established an ex vivo model for neovascularization allows to study the morphogenetic events of complex new vessel formation that includes all layers of mature blood vessels, a significant advantage over the assays that employ monolayer endothelial cell cultures. Moreover, in contrast to assays employing endothelial cells monocultures, both angiogenic and vasculogenic events take place during new vessel formation in ARA although the exact contribution of these two processes to new vessel formation cannot be easily distinguished in conventional ARA. Thus, in this study, a modified protocol for the ARA (mdARA) was established by either removing or keeping the aortic adventitia in place. The mdARA allows to distinguish the role of VW-SPCs from those of other aortic layers. The present data show that angiogenic sprouting from mature aortic endothelium was markedly delayed when the adventitial layer was removed. Furthermore, the network between the capillary-like sprouts was significantly reduced in absence of aortic adventitia. Moreover, the stabilization of new sprouts by assembling the NG2+ pericyte-like cells that enwrapped the endothelial sprouts from the outside was improved when the adventitial layer remained in place. Next, mimicking the tumor-vessel adventitia-interaction, multicellular tumor spheroids (MCTS) and aortic rings (ARs) with or without adventitia of C57BL/6-Tg (UBC-GFP) mice were confronted within the collagen gel and cultured ex vivo. This 3D model enabled analysis of the mobilization, migration and capillary-like sprouts formation by VW-SPCs within tumor-vessel wall-interface in comparison to tumor-free side of the ARs. Interestingly, while MCTS preferred the uptake of single vascular adventitia-derived cells, neural spheroids were directly penetrated by capillary-like structures that were sprouted from the aortic adventitia. In summary, the model established in this work allows to study new vessel formation by both postnatal vasculogenesis and angiogenesis under same conditions. It can be applied in various mouse models including reporter mouse models, e.g. Cxcr1 CreER+/mTmG+/- mice, in which GFP-marked macrophages of the vessel wall were directly observed as they mobilized from their niche and migrated into collagen gel. Another benefit of the model is that it can be used for testing different factors such as small molecules, growth factors, cytokines, and drugs with both pro- and anti-angiogenic/vasculogenic effects.},
  language  = {en}
}
@phdthesis{Rademaker2020,
  author    = {Rademaker, Manuel Elias},
  title     = {Composite-based Structural Equation Modeling},
  doi       = {10.25972/OPUS-21593},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215935},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Structural equation modeling (SEM) has been used and developed for decades across various domains and research fields such as, among others, psychology, sociology, and business research. Although no unique definition exists, SEM is best understood as the entirety of a set of related theories, mathematical models, methods, algorithms, and terminologies related to analyzing the relationships between theoretical entities -- so-called concepts --, their statistical representations -- referred to as constructs --, and observables -- usually called indicators, items or manifest variables. This thesis is concerned with aspects of a particular strain of research within SEM -- namely, composite-based SEM. Composite-based SEM is defined as SEM involving linear compounds, i.e., linear combinations of observables when estimating parameters of interest. The content of the thesis is based on a working paper (Chapter 2), a published refereed journal article (Chapter 3), a working paper that is, at the time of submission of this thesis, under review for publication (Chapter 4), and a steadily growing documentation that I am writing for the R package cSEM (Chapter 5). The cSEM package -- written by myself and my former colleague at the University of Wuerzburg, Florian Schuberth -- provides functions to estimate, analyze, assess, and test nonlinear, hierarchical and multigroup structural equation models using composite-based approaches and procedures. In Chapter 1, I briefly discuss some of the key SEM terminology. Chapter 2 is based on a working paper to be submitted to the Journal of Business Research titled "Assessing overall model fit of composite models in structural equation modeling". The article is concerned with the topic of overall model fit assessment of the composite model. Three main contributions to the literature are made. First, we discuss the concept of model fit in SEM in general and composite-based SEM in particular. Second, we review common fit indices and explain if and how they can be applied to assess composite models. Third, we show that, if used for overall model fit assessment, the root mean square outer residual covariance (RMS_theta) is identical to another well-known index called the standardized root mean square residual (SRMR). Chapter 3 is based on a journal article published in Internet Research called "Measurement error correlation within blocks of indicators in consistent partial least squares: Issues and remedies". The article enhances consistent partial least squares (PLSc) to yield consistent parameter estimates for population models whose indicator blocks contain a subset of correlated measurement errors. This is achieved by modifying the correction for attenuation as originally applied by PLSc to include a priori assumptions on the structure of the measurement error correlations within blocks of indicators. To assess the efficacy of the modification, a Monte Carlo simulation is conducted. The paper is joint work with Florian Schuberth and Theo Dijkstra. Chapter 4 is based on a journal article under review for publication in Industrial Management \& Data Systems called "Estimating and testing second-order constructs using PLS-PM: the case of composites of composites". The purpose of this article is threefold: (i) evaluate and compare common approaches to estimate models containing second-order constructs modeled as composites of composites, (ii) provide and statistically assess a two-step testing procedure to test the overall model fit of such models, and (iii) formulate recommendation for practitioners based on our findings. Moreover, a Monte Carlo simulation to compare the approaches in terms of Fisher consistency, estimated bias, and RMSE is conducted. The paper is joint work with Florian Schuberth and J{\"o}rg Henseler.},
  subject      = {trukturgleichungsmodell},
  language  = {en}
}
@techreport{ConradMorperBuschNetzbandetal.2019,
  type      = {Working Paper},
  author    = {Conrad, Christopher and Morper-Busch, Lucia and Netzband, Maik and Teucher, Mike and Sch{\"o}nbrodt-Stitt, Sarah and Schorcht, Gunther and Dukhovny, Viktor},
  title     = {WUEMoCA Water Use Efficiency Monitor in Central Asia Informed Decision-Making in Land and Water Resources Management},
  doi       = {10.25972/OPUS-19193},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191934},
  pages     = {1-12},
  year      = {2019},
  abstract  = {WUEMoCA is an operational scientific webmapping tool for the regional monitoring of land and water use efficiency in the irrigated croplands of the transboundary Aral Sea Basin that is shared by Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan, and Afghanistan. Satellite data on land use, crop pro-duction and water consumption is integrated with hydrological and economic information to provide of a set indicators. The tool is useful for large-scale decisions on water distribution or land use, and may be seen as demonstrator for numerous applications in practice, that require independent area-wide spatial information.},
  subject      = {Zentralasien},
  language  = {en}
}