@phdthesis{Gebert2017,
  author    = {Gebert, Steffen Christian},
  title     = {Architectures for Softwarized Networks and Their Performance Evaluation},
  issn      = {1432-8801},
  doi       = {10.25972/OPUS-15063},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150634},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {This thesis contributes to several issues in the context of SDN and NFV, with an emphasis on performance and management. The main contributions are guide lines for operators migrating to software-based networks, as well as an analytical model for the packet processing in a Linux system using the Kernel NAPI.},
  subject      = {Telekommunikationsnetz},
  language  = {en}
}
@phdthesis{Kramer2017,
  author    = {Kramer, Christian},
  title     = {Investigation of Nanostructure-Induced Localized Light Phenomena Using Ultrafast Laser Spectroscopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150681},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {In recent years, the interaction of light with subwavelength structures, i.e., structures that are smaller than the optical wavelength, became more and more interesting to scientific research, since it provides the opportunity to manipulate light-induced dynamics below the optical diffraction limit. Specifically designed nanomaterials can be utilized to tailor the temporal evolution of electromagnetic fields at the nanoscale. For the investigation of strongly localized processes, it is essential to resolve both their spatial and their temporal behavior. The aim of this thesis was to study and/or control the temporal evolution of three nanostructure-induced localized light phenomena by using ultrafast laser spectroscopy with high spatial resolution. In Chapter 4, the absorption of near-infrared light in thin-film a-Si:H solar cells was investigated. Using nanotextured instead of smooth interfaces for such devices leads to an increase of absorption from < 20\% to more than 50\% in the near-infrared regime. Time-resolved experiments with femtosecond laser pulses were performed to clarify the reason for this enhancement. The coherent backscattered radiation from nanotextured solar cell devices was measured as a function of the sample position and evaluated via spectral interferometry. Spatially varying resonance peaks in the recorded spectra indicated the formation of localized photonic modes within the nanotextured absorber layers. In order to identify the modes separately from each other, coherent two-dimensional (2D) nanoscopy was utilized, providing a high spatial resolution < 40 nm. In a nanoscopy measurement on a modified device with an exposed nanotextured a-Si:H absorber layer, hot-spot electron emission was observed and confirmed the presence of localized modes. Fitting the local 2D nanospectra at the hot-spot positions enabled the determination of the resonance frequencies and coherence lifetimes of the modes. The obtained lifetime values varied between 50 fs and 130 fs. Using a thermionic emission model allowed the calculation of the locally absorbed energy density and, with this, an estimation of the localization length of the photonic modes (≈1 μm). The localization could be classified by means of the estimated localization length and additional data evaluation of the backscattered spectra as strong localization ─ the so-called Anderson localization. Based on the experimental results, it was concluded that the enhanced absorption of near-infrared light in thin-film silicon solar cells with nanotextured interfaces is caused by the formation of strongly localized photonic modes within the disordered absorber layers. The incoming near-infrared light is trapped in these long-living modes until absorption occurs. In Chapter 5, a novel hybridized plasmonic device was introduced and investigated in both theory and experiment. It consists of two widely separated whispering gallery mode (WGM) nanoantennas located in an elliptical plasmonic cavity. The goal was to realize a periodic long-range energy transfer between the nanoantennas. In finite-difference time-domain (FDTD) simulations, the device was first optimized with respect to strong coupling between the localized antenna modes and the spatially-extended cavity mode. The geometrical parameters of the antennas and the cavity were adjusted separately so that the m="0" antenna mode and the cavity mode were resonant at λ="800 nm" . A high spatial overlap of the modes was achieved by positioning the two antennas in the focal spots of the cavity, leading to a distance between the antenna centers of more than twice the resonant wavelength of the modes. The spectral response of the optimized device revealed an energy splitting of the antenna and the cavity mode into three separated hybridized eigenmodes within an energy range of about 90 meV due to strong coupling. It could be well reproduced by a simple model of three coupled Lorentzian oscillators. In the time domain, an oscillatory energy transfer between both antennas with a period of 86 fs and an energy transfer efficiency of about 7\% was observed for single-pulse excitation. For the experiments, devices with cavities and antennas of varying size were fabricated by means of focused-ion-beam (FIB) milling. Time-resolved correlation measurements were performed with high spatial and temporal resolution by using sequences of two femtosecond laser pulses for excitation and photoemission electron microscopy (PEEM) for detection. Local correlation traces at antennas in resonant devices, i.e., devices with enhanced electron emission at both antenna positions, were investigated and reconstructed by means of the coupled-oscillator model. The corresponding spectral response revealed separated peaks, confirming the formation of hybridized eigenmodes due to strong coupling. In a subsequent simulation for single-pulse excitation, one back-and-forth energy transfer between both antennas with an energy transfer efficiency of about 10\% was observed. Based on the theoretical and experimental results, it was demonstrated that in the presented plasmonic device a periodic long-range energy transfer between the two nanoantennas is possible. Furthermore, the coupled-oscillator model enables one to study in depth how specific device properties impact the temporal electric-field dynamics within the device. This can be exploited to further optimize energy transfer efficiency of the device. Future applications are envisioned in ultrafast plasmonic nanocircuitry. Moreover, the presented device can be employed to realize efficient SPP-mediated strong coupling between widely separated quantum emitters. In Chapter 6, it was investigated in theory how the local optical chirality enhancement in the near field of plasmonic nanostructures can be optimized by tuning the far-field polarization of the incident light. An analytic expression was derived that enables the calculation of the optimal far-field polarizations, i.e., the two far-field polarizations which lead to the highest positive and negative local optical chirality, for any given nanostructure geometry. The two optimal far-field polarizations depend on the local optical response of the respective nanostructure and thus are functions of both the frequency ω and the position r. Their ellipticities differ only in their sign, i.e., in their direction of rotation in the time domain, and the angle between their orientations, i.e., the angle between the principal axes of their ellipses, is ±π/"2" . The handedness of optimal local optical chirality can be switched by switching between the optimal far-field polarizations. In numerical simulations, it was exemplarily shown for two specific nanostructure assemblies that the optimal local optical chirality can significantly exceed the optical chirality values of circularly polarized light in free space ─ the highest possible values in free space. The corresponding optimal far-field polarizations were different from linear and circular and varied with frequency. Using femtosecond polarization pulse shaping provides the opportunity to coherently control local optical chirality over a continuous frequency range. Furthermore, symmetry properties of nanostructures can be exploited to determine which far-field polarization is optimal. The theoretical findings can have impact on future experimental studies about local optical chirality enhancement. Tuning the far-field polarization of the incident light offers a promising tool to enhance chirally specific interactions of local electromagnetic fields with molecular and other quantum systems in the vicinity of plasmonic nanostructures. The presented approach can be utilized for applications in chiral sensing of adsorbed molecules, time-resolved chirality-sensitive spectroscopy, and chiral quantum control. In conclusion, each of the localized light phenomena that were investigated in this thesis ─ the enhanced local absorption of near-infrared light due to the formation of localized photonic modes, the periodic long-range energy transfer between two nanoantennas within an elliptical plasmonic cavity, and the optimization of local optical chirality enhancement by tuning the far-field polarization of the incident light ─ can open up new perspectives for a variety of future applications. .},
  subject      = {Ultrakurzzeitspektroskopie},
  language  = {en}
}
@unpublished{BaumannWillaschekKertessSzlaninkaetal.2017,
  author    = {Baumann, Christoph and Willaschek, Christian and Kertess-Szlaninka, Tuende and Lang, Johanna and Buchhorn, Reiner},
  title     = {Implementing high energy liquid nutrition, omega-3 fatty acids and nutritional supplements for the treatment of anorexia nervosa},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150430},
  year      = {2017},
  abstract  = {Objective: To examine the effects of two different treatment approaches on the course of anorexia nervosa (AN) over time. Methods: The subjects were 27 hospitalized AN patients (mean age: 14.91 years; mean BMI: 14.58; mean height: 163.56) . In our retrospective analysis we compared weight gain in two groups. While one group was treated with a standard oral refeeding protocol (historical control) through January 2013 (N=16), the second group (highly standardized refeeding protocol) received a high energy liquid nutrition and nutritional supplements including omega-3 fatty acids (N=11). Results: On admission, the two groups were comparable in terms of height, weight, age and heart rate. At the end of our monitoring time frame of 25 days, weight gain was 121.4\% higher in the highly standardized refeeding protocol group than in the historical control group (66.5 ±52.4 vs 147.3 ±55.7 grams/day; t-Test p=0.004; CI95\%: 29.3-132.2). About 45\% of our patients stated they were vegetarians at admission. However, we could not identify a vegetarian diet as a statistically significant negative prognostic factor for weight gain. Discussion: The highly standardized refeeding protocol seems to be helpful in malnourished AN patients to improve weight gain without enhancing the risk of a refeeding syndrome. Because of an increasing energy turnover, caloric intake should be adjusted during refeeding.},
  subject      = {Anorexia nervosa},
  language  = {en}
}
@phdthesis{Glasgow2017,
  author    = {Glasgow, Rupert},
  title     = {The Minimal Self},
  publisher = {W{\"u}rzburg University Press},
  address   = {W{\"u}rzburg},
  isbn      = {978-3-95826-052-8 (print)},
  doi       = {10.25972/WUP-978-3-95826-053-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145252},
  school      = {W{\"u}rzburg University Press},
  pages     = {392},
  year      = {2017},
  abstract  = {The aim of The Minimal Self is to undertake a conceptual analysis of the term 'self' and thereby establish the minimal conditions that must be met to ascribe selfhood to an entity. This conceptual analysis focuses on what is termed 'intrinsic reflexivity', which is taken as the defining feature of selfhood. Three underlying categories of intrinsic reflexivity are distinguished: self-maintenance, self-reproduction and self-containment. These three fundamental categories provide a framework within which it is possible to distinguish entities that can be designated 'selves' from entities that are merely 'self-like', thus establishing the logical preconditions for the 'emergence' of selfhood. By examining the fuzzy borderlines between selves and the merely self-like as manifest in phenomena such as dissipative systems, genetic material, viruses and bacteria, it becomes possible to ascertain a form of 'minimal selfhood', a mode of being shared by all selves qua selves. Free-living single-celled organisms such as protozoa are paradigmatic instances of minimal selfhood to the extent that they can be characterized in terms of the three intrinsically reflexive processes of self-maintenance, self-reproduction and self-containment. Minimal selfhood is also presupposed by more complex multicellular selves such as animals. Such an analysis is found to shed light on the origin of life and on the nature of organisms and biological individuals.},
  subject      = {Selbst},
  language  = {en}
}
@phdthesis{Will2017,
  author    = {Will, Sebastian},
  title     = {Development of a presence model for driving simulators based on speed perception in a motorcycle riding simulator},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149748},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Driving simulators are powerful research tools. Countless simulator studies have contributed to traffic safety over the last decades. Constant improvements in simulator technology call for a measureable scale to assess driving simulators with regard to their utility in human factors research. A promising psychological construct to do so is presence. It is commonly defined as the feeling of being located in a remote or virtual environment that seems to be real. Another aspect of presence describes the ability to act there successfully. The main aim of this thesis is to develop a presence model dedicated to the application in driving simulators. Established models have been combined and extended in order to gain a comprehensive model of presence that allows understanding its emergence and deriving recommendations on how to design or improve driving simulators. The five studies presented in this thesis investigate specific postulated model components and their interactions. All studies deal with motorcycling or a motorcycle riding simulator as exemplary field of application. The first study used a speed estimation task to investigate the contribution of different sensory cues to presence. While visualization plays a particularly important role, further improvements could be achieved by adding more consistent sensory stimuli to the virtual environment. Auditory, proprioceptive and vestibular cues have been subject to investigation. In the second study, the speed production method was applied. It confirmed the positive contribution of action to presence as predicted by psychocybernetic models. The third study dealt with the effect of training on presence. Hence, no positive effect was observed. The fourth study aimed at replicating previous findings on sensory fidelity and diversity in a more complex riding situation than only longitudinal vehicle control. The riders had to cross an unexpectedly appearing deep pit with the virtual motorcycle. The contribution of more consistent sensory stimulation on presence was successfully shown in this scenario, too. The final study was a real riding experiment that delivered reference values for the speed estimation capabilities of motorcycle riders. Besides higher variations in the simulator data, the general speed estimation performance was on a comparable level. Different measures, such as subjective ratings, behavioral responses, performance, and physiological reactions, have been applied as presence indicators. These studies' findings deliver evidence for the meaningful application of the proposed presence model in driving simulator settings. The results suggest that presence can be interpreted as a quality measure for perception in virtual environments. In line with psychocybernetic models, taking action, which is seen as controlling perception, enhances this quality even further. Describing the psychological construct of presence in a theoretical framework that takes the diversity of perception and action in driving simulator settings into account closes a gap in traffic psychological research.},
  subject      = {Fahrsimulator},
  language  = {en}
}
@phdthesis{GallegoValencia2017,
  author    = {Gallego Valencia, Juan Pablo},
  title     = {On Runge-Kutta discontinuous Galerkin methods for compressible Euler equations and the ideal magneto-hydrodynamical model},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148874},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {An explicit Runge-Kutta discontinuous Galerkin (RKDG) method is used to device numerical schemes for both the compressible Euler equations of gas dynamics and the ideal magneto- hydrodynamical (MHD) model. These systems of conservation laws are known to have discontinuous solutions. Discontinuities are the source of spurious oscillations in the solution profile of the numerical approximation, when a high order accurate numerical method is used. Different techniques are reviewed in order to control spurious oscillations. A shock detection technique is shown to be useful in order to determine the regions where the spurious oscillations appear such that a Limiter can be used to eliminate these numeric artifacts. To guarantee the positivity of specific variables like the density and the pressure, a positivity preserving limiter is used. Furthermore, a numerical flux, proven to preserve the entropy stability of the semi-discrete DG scheme for the MHD system is used. Finally, the numerical schemes are implemented using the deal.II C++ libraries in the dflo code. The solution of common test cases show the capability of the method.},
  subject      = {Eulersche Differentialgleichung},
  language  = {en}
}
@phdthesis{Messerer2017,
  author    = {Messerer, Regina},
  title     = {Synthesis of Dualsteric Ligands for Muscarinic Acetylcholine Receptors and Cholinesterase Inhibitors},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149007},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {The study is dealing with the synthesis and pharmacological investigation of newly designed dualsteric ligands of muscarinic acetylcholine receptors belonging to the superfamily of G protein-coupled receptors. Such bipharmacophoric ligands combine the advantages of the orthosteric binding site (high-affinity) and of the topographically distinct allosteric binding site (subtype-selectivity) resulting in compounds with reduced side effects. This opens the way to a new therapeutic approach in the treatment of e.g. chronic pain, drug withdrawal, Parkinson`s and Alzheimer`s disease. Furthermore, the newly synthesized dualsteric compounds were pharmacologically investigated in order to get a better understanding of the activation and signaling processes in muscarinic acetylcholine receptors, especially with regard to partial agonism. The development of the "dynamic ligand binding" concept offers new perspectives for ligand binding and signaling at G protein-coupled receptors. GPCRs are no longer considered as simple on/off switches. Dualsteric ligands can bind in a dualsteric pose, reflecting an active receptor state as well as in a purely allosteric binding pose, characterized by an inactive receptor state resulting in partial agonism. The degree of partial agonism depends on the ratio of active versus inactive receptor populations. On this basis, orthosteric/orthosteric hybrid ligands consisting of the antagonist atropine and scopolamine, respectively, as well as of the agonist iperoxo and isoxazole, respectively, linked via different alkyl chain length were synthesized in order to investigate partial agonism (Figure 1). Figure 1: Structures of the synthesized iperoxo/isoxazole-atropine/scopolamine-hybrids. Furthermore, different sets of quaternary and tertiary homodimers consisting either of two iperoxo or two acetylcholine units were synthesized in order to study their extent on partial agonism (Figure 2). The two agonists were connected by varying alkyl chain length. Binding studies on CHO-hM2 cells of the quaternary compounds revealed that dimerization of the agonist results in a loss of potency. The iperoxo-dimers reached higher maximum effects on the Gi- as well as on the Gs pathway in comparison to the acetylcholine-dimers. Besides the choice of the orthosteric building block (potency of the agonist), the alkyl chain length is also crucial for the degree of partial agonism. Figure 2: Structures of the synthesized quat./tert. iperoxo/acetylcholine-homodimers. Quinolone-based hybrids connected to the superagonist iperoxo and to the endogenous ligand acetylcholine, respectively, linked through an alkyl chain of different length were synthesized in order to develop further partial agonists (Figure 3). FRET studies confirmed M1 subtype-selectivity as well as linker dependent receptor response. The greatest positive FRET signal was observed with quinolone-C6-iper resulting from a positive cooperativity between the two separated moieties, alloster and orthoster. However, the corresponding hybrids with a longer linker led to an inverse FRET signal indicating a different binding mode, e.g. purely allosteric, in contrast to the shorter linked hybrids. Furthermore, the flexible alkyl spacer was replaced by a rigidified linker resulting in the hybrid quinolone-rigid-iperoxo (Figure 3). FRET studies on the M1 receptor showed reduced FRET kinetics, resulting from interactions between the bulky linker and the aromatic lid, located between the orthosteric and allosteric binding site. A bitopic binding mode of the rigidified hybrid is presumed. For further clarity, mutational studies are necessary. Figure 3: M1-selective hybrid compounds. Another aim of this work was the design and synthesis of new hybrid compounds, acting as agonists at the M1 and M2 receptor and as inhibitors for AChE and BChE in the context of M. Alzheimer. Several sets of hybrid compounds consisting of different pharmacophoric units (catalytic active site: phthalimide, naphthalimide, tacrine; peripheric anionic site: iperoxo, isoxazole) linked through a polymethylene chain of varying length were synthesized. Tac-C10-iper (Figure 4), consisting of tacrine and the superagonist iperoxo linked by a C10 polymethylene spacer, was found to have excellent anticholinesterase activity for both AChE (pIC50 = 9.81) and BChE (pIC50 = 8.75). Docking experiments provided a structural model to rationalize the inhibitory power towards AChE. Additionally, the tacrine related hybrids showed affinity to the M1 and M2 receptor. Such compounds, addressing more than one molecular target are favorable for multifactorial diseases such as Alzheimer. Figure 4: Structure of the most active compound regarding anticholinesterase activity. In summary, the choice of the pharmacophoric units, their connecting point as well as the nature, length, and flexibility of the linker play an important role for the activity of designed bivalent ligands. A shorter linker length cannot bridge both binding sites simultaneously in contrast to longer linker chains. On the other hand, too long linker chains can result in unwanted steric interactions. Further investigations with respect to structural variations of hybrid compounds, with or without quaternary ammonium groups, are necessary in the light of drug development.},
  subject      = {Cholinesteraseinhibitor},
  language  = {en}
}
@phdthesis{Gao2017,
  author    = {Gao, Shiqiang},
  title     = {Characterizing new photoreceptors to expand the Optogenetic toolbox},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112941},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Optogenetics is a method to control the cell activity with light by expression of a natural or engineered photoreceptor via genetic modification technology. Optogenetics early success came with the light-gated cation channel "Channelrhodopsin-2" in neurons and expanded from neuroscience to other research fields such as cardiac research and cell signaling, also due to the enrichment by new photoreceptors. In this study, I focus on searching and characterizing new photoreceptors to expand the optogenetic tool box. In this work I characterize three newly discovered microbial rhodopsins and some engineered mutants of them. The first rhodopsin is a proton pump from the diatom Fragilariopsis cylindrus, Fragilariopsis Rhodopsin or abbreviated: FR. I cloned the full-length FR and proved it to be a light-activated proton pump with high efficacy in comparison to Bacteriorhodopsin (BR). During this study, I also developed a new method to improve the plasma membrane targeting of several microbial rhodopsins. I also obtained a FR mutant (channel-like FR or chFR) which behaves like a light-gated proton channel. FR can be used for optogenetic hyperpolarization or alkalization of a cell while the chFR could be used for depolarization or lowering of the cellular pH. The induction of FR expression under iron-limited conditions in the diatom indicated an alternative energy generation mechanism of F. cylindrus when iron-containing enzymes are scarce. I then characterized a new microbial rhodopsin with novel light-regulated Guanylyl Cyclase (GC) activity. This rhodopsin guanylyl cyclase from the fungus Blastocladiella emersonii (B.e. CyclaseOpsin or BeCyclOp) has been proven by me to be an efficient light-gated GC with high specificity and fast kinetics. BeCyclOp also has a novel structure with eight transmembrane helices, containing a long cytosolic N-terminus which participates in the tight regulation of the GC activity. In collaboration with Prof. Alexander Gottschalk (Univ. Frankfurt/M.), BeCyclOp has been tested in muscle cells and sensory neurons of Caenorhabditis elegans and proven to be a powerful optogenetic tool in a living animal. I also generated a BeCyclOp mutant with enhanced light sensitivity. Already more than ten years ago, guanylyl cyclase rhodopsins were suggested to exist in Chlamydomonas reinhardtii by analyzing genomic sequence data. But until now no functional proof existed. By further cloning and sequencing I discovered such a rhodopsin with light-regulated guanylyl cyclase activity. This functional Cyclaseopsin (COP6c) is quite different to BeCyclOp, as it was proven to be a light-inhibited GC. Cop6c is much larger than BeCyclOp with a His-Kinase and a response regulator domain between the rhodopsin and the cyclase domain. I also introduced a new strategy for generating optogenetic tools by fusing the photoactivated adenylyl cyclase bPAC to two different CNG channels. These new tools function via light-gated cAMP production and subsequent CNG channel activation. These tools combined the properties of bPAC (highly sensitive to blue light) and CNG channels (high single-channel conductance and high Ca2+ permeability), as demonstrated by expression in Xenopus oocytes. As a further benefit the fusing of bPAC to CNG channels leads to a bPAC with a more than tenfold reduced dark activity which is a valuable improvement for bPAC itself as an optogenetic tool.},
  subject      = {Photorezeptor},
  language  = {en}
}
@phdthesis{LeBlancSoto2017,
  author    = {Le Blanc Soto, Solange},
  title     = {Role of FGF signaling in the adipogenic and osteogenic differentiation of human bone marrow stromal cells in a three-dimensional \(in\) \(vitro\) model},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147659},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Adult human skeletal stem cells are considered to give rise to the bone marrow stromal compartment, including bone-forming osteoblasts and marrow adipocytes. Reduced osteogenesis and enhanced adipogenesis of these skeletal progenitors may contribute to the bone loss and marrow fat accumulation observed during aging and osteoporosis, the main disorder of bone remodeling. Concordantly, in vitro evidence indicates that adipogenic and osteogenic differentiation of human bone marrow stromal cells (hBMSCs) display an inverse relationship under numerous conditions. Hence, the identification of factors modulating inversely both differentiation pathways is of great therapeutic interest. Based on mRNA expression analysis of inversely regulated genes after switching differentiation conditions, our group had previously proposed that fibroblast growth factor 1 (FGF1) might play such a modulator role in hBMSC differentiation. The main aim of this work was, therefore, to investigate the role of FGF1 signaling in the adipogenic and osteogenic differentiation of hBMSCs using a three-dimensional (3D) culture system based on collagen type I hydrogels in order to better mimic the natural microenvironment. Adipogenic and osteogenic differentiation of hBMSCs embedded in collagen gels was successfully established. Treatment with recombinant human FGF1 (rhFGF1), as well as rhFGF2, throughout differentiation induction was found to exert a dose-dependent inhibitory effect on adipogenesis in hBMSCs. This inhibitory effect was found to be reversible and dependent on FGF receptors (FGFR) signaling, given that simultaneous pharmacological blockage of FGFRs rescued adipogenic differentiation. Additionally, matrix mineralization under osteogenic induction was also inhibited by rhFGF1 and rhFGF2 in a dose-dependent manner. A transient treatment with rhFGF1 and rhFGF2 during an expansion phase, however, enhanced proliferation of hBMSCs without affecting the differentiation capacity, although matrix mineralization under osteogenic conditions was hindered. Additionally, rhFGF1 and rhFGF2 treatments affected the matrix remodeling ability of hBMSCs, which displayed alterations in the cytoskeletal phenotype and the expression patterns of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). On the other hand, inhibition of FGFR signaling throughout differentiation induction elicited a strong enhancement of matrix mineralization under osteogenic conditions but had no significant effect on adipocyte formation under adipogenic induction. IX In conclusion, FGF1 and FGF2 signaling was found to support the expansion of bone marrow stromal precursors with adipogenic and osteogenic capacities, to hinder adipogenic and osteogenic differentiation if continuously present during differentiation induction and to alter the matrix remodeling ability of hBMSCs within a 3D collagenous microenvironment.},
  subject      = {Fettzelle},
  language  = {en}
}
@phdthesis{Ezenwa2017,
  author    = {Ezenwa, Paul Chinedu},
  title     = {The Value of Human Dignity: A Socio-Cultural Approach to Analyzing the Crisis of Values among Igbo People of Nigeria},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147603},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Starting from conception till death, man as a being relates with others. In this relationship he often encounters lots of problems that threaten his existence. One of them is the threat to his dignity. This experience is vivid in many countries particularly in Africa. But my work is limited to an ethnic group in Nigeria, namely Igbo people. The work discloses the extent 'displacement of value' in Igboland has contributed to the devaluation of human dignity and the attempts made to combat it. This displacement resulted in what we can call "value crisis". Some elements, like Igbo culture and cultural communication with foreign cultures that have tentacles in modernized orientation, are discussed as 'transmission carriers'. In order to x-ray properly the heart of this research and communicate the necessary messages, the work is presented in six chapters. However, this summary will not be presented in chapters. Thus the need for a research on the reason for the failings and crisis of approach regarding this aspect of Igbo life that deals with the value of human dignity. This comes to term with the question which asked has the interest in the enhancement of the dignity of man waned because the effort towards this goal seem futile and unnecessary…Or is human dignity something we care about but take for granted as a cultural inheritance that no longer needs defence?" This question arouses thoughts on the value of HD. The entire work tried to justify the view that the protection of HD is for all times a true assignment of all. This must neither be considered to be relevant only for a time nor only for a portion or a group of individuals. Thus a special attention on this regard is demanded especially in modern day Igbo society.},
  subject      = {Nigeria},
  language  = {en}
}
@phdthesis{Chikezie2017,
  author    = {Chikezie, Aloysius Cheta},
  title     = {THE VALUE OF WORK IN NIGERIA with Reference to Laborem Exercens},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147592},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Work is seen by many thinkers as the fundamental dimension of man`s existence on earth. Through work, he provides his basic necessities on earth and co-operate with God in the work of creation. He received this mandate to work from the very beginning of creation by God. In carrying out this mandate, man every human being reflects the very action of the creator of the Universe. God worked and intended that man who is created in His image and likeness continues the work of creation by working. Even though Man suffers and sweats through work and yet, in spite of all this toil-perhaps in a sense because of it - work is a good thing for man. It is not only good in the sense that it is useful or something to enjoy; it is also good as being something worthy, that is to say something that corresponds to man's dignity that expresses this dignity and increases it. This project examines man as a creature called to work and born into work. It is true that through work, man provides himself and his family with the basic necessities of life and everyday needs for the reason he charges wages for his sweat. Work goes beyond and should exceed the boundaries of the material benefit that comes out of it to the satisfaction and fulfilment for the very purpose we should work. The modern society has attached so much importance to money and material possession, the question then is how do we go along working in the spirit of improvement and renewal of the earth? The modern man understands work only as a means of making his daily bread. For this reason, he engages himself in an occupation that he has little or no interest in. He ends up quarrelling everyday with the people that he or she is supposed to serve through work. The result is low work output and waste of talents and the society loses an opportunity for improvement as every creature is supposed to contribute uniquely. A good example is Nigeria, Africa's most populous nation with a population estimate of about over 170,000,000 people and the sixth Oil producing Nation.},
  subject      = {Nigeria},
  language  = {en}
}
@phdthesis{Moradi2017,
  author    = {Moradi, Mehri},
  title     = {Differential roles of α-, β- and γ-actin isoforms in regulation of cytoskeletal dynamics and stability during axon elongation and collateral branch formation in motoneurons},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147453},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {In highly polarized cells like neurons, cytoskeleton dynamics play a crucial role in establishing neuronal connections during development and are required for adult plasticity. Actin turnover is particularly important for neurite growth, axon path finding, branching and synaptogenesis. Motoneurons establish several thousand branches that innervate neuromuscular synapses (NMJs). Axonal branching and terminal arborization are fundamental events during the establishment of synapses in motor endplates. Branching process is triggered by the assembly of actin filaments along the axon shaft giving rise to filopodia formation. The unique contribution of the three actin isoforms, α-, β- and γ-actin, in filopodia stability and dynamics during this process is not well characterized. Here, we performed high resolution in situ hybridization and qRT-PCR and showed that in primary mouse motoneurons α-, β- and γ-actin isoforms are expressed and their transcripts are translocated into axons. Using FRAP experiments, we showed that transcripts for α-, β- and γ-actin become locally translated in axonal growth cones and translation hot spots of the axonal branch points. Using live cell imaging, we showed that shRNA depletion of α-actin reduces dynamics of axonal filopodia which correlates with reduced number of collateral branches and impairs axon elongation. Depletion of β-actin correlates with reduced dynamics of growth cone filopoida, disturbs axon elongation and impairs presynaptic differentiation. Also, depletion of γ-actin impairs axonal growth and decreases axonal filopodia dynamics. These findings implicate that actin isoforms accomplish unique functions during development of motor axons. Depletions of β- and γ-actin lead to compensatory upregulation of other two isoforms. Consistent with this, total actin levels remain unaltered and F-actin polymerization capacity is preserved. After the knockdown of either α- or γ-actin, the levels of β-actin increase in the G-actin pool indicating that polymerization and stability of β-actin filaments depend on α- or γ-actin. This study provides evidence both for unique and overlapping function of actin isoforms in motoneuron growth and differentiation. In the soma of developing motoneurons, actin isoforms act redundantly and thus could compensate for each other's loss. In the axon, α-, β- and γ-actin accomplish specific functions, i.e. β-actin regulates axon elongation and plasticity and α- and γ-actin regulate axonal branching. Furthermore, we show that both axonal transport and local translation of α-, β- and γ-actin isoforms are impaired in Smn knockout motoneurons, indicating a role for Smn protein in RNA granule assembly and local translation of these actin isoforms in primary mouse motoneurons.},
  subject      = {Motoneuron},
  language  = {en}
}
@phdthesis{Bruehlmann2017,
  author    = {Br{\"u}hlmann, David},
  title     = {Tailoring Recombinant Protein Quality by Rational Media Design},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147345},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Nowadays, more than half of the biotherapeutics are produced in mammalian cell lines as a result of correct protein folding and assembly as well as their faculty to bring about a variety of post-translational modifications. The widespread progression of biosimilars has moved the focus in mammalian cell-culture process development. Thereby, the modulation of quality attributes of recombinant therapeutic proteins has increasingly gained importance from early process development stages. Protein quality directly shapes the clinical efficacy and safety in vivo, and therefore, the control of the complex post-translational modifications, such as glycosylation (e.g. high mannose, fucosylation, galactosylation and sialylation), charge variants, aggregates and low-molecular-weight species formation, is pivotal for efficient receptor binding and for triggering the desired immune responses in patients. In the frame of biosimilar development, product quality modulation methods using the potential of the host cell line are particularly sought after to match the quality profile of the targeted reference medicinal product (RMP) as closely as possible. The environment the cell is dwelling in directly influences its metabolism and the resulting quality profile of the expressed protein. Thereby the cell culture medium plays a central role in upstream manufacturing. In this work, concentration adjustment of selected media components and supplementation with a variety of compounds was performed to alter various metabolic pathways, enzyme activities and in some cases the gene expression levels of Chinese Hamster Ovary (CHO) cells in culture. The supplementation of cell culture medium with the trisaccharide raffinose in fed-batch cultures entailed an increase of the abundance of high mannose glycans in two different CHO cell lines. Raffinose especially favored mannose 5 glycans. At the same time, it impaired cell culture performance, induced changes on the intracellular nucleotide levels and even varied the expression levels of glycosylation-related genes. Supplementation with a number of galactosyltransferase inhibiting compounds, in particular fluorinated galactose analogs (alpha- and beta-2F-peracetyl-galactose), consistently decreased the production of galactosylated monoclonal antibodies (mAb). By means of targeted addition during the culture rather than at the beginning, the inhibition was further increased, while limiting detrimental effects on both growth and productivity. High-throughput screening in 96-deepwell plates showed that spermine and L-ornithine also reduced the level of galactosylation. On the other hand, exploratory screening of a variety of potentially disulfide-bridge-reducing agents highlighted that the inherent low-molecular-species level of the proprietary platform cell culture process was likely due to favored reduction. This hypothesis was reinforced by the observation that supplementation of cysteine and N-acetylcysteine promoted fragmentation. Additionally, fragmentation decreased with higher protein expression. At that point, aiming to improve the efficiency in process development, a rational experimental design method was developed to identify and to define the optimal concentration range of quality modulating compounds by calling on a combination of high throughput fed-batch testing and multivariate data analysis. Seventeen medium supplements were tested in five parallel 96-deepwell plate experiments. The selection process of promising modulators for the follow-up experiment in shake tubes consisted in a three-step procedure, including principal component analysis, quantitative evaluation of their performance with respect to the specifications for biosimilarity and selection following a hierarchical order of decisions using a decision tree. The method resulted in a substantial improvement of the targeted glycosylation profile in only two experimental rounds. Subsequent development stages, namely validation and transfer to industrial-scale facilities require tight control of product quality. Accordingly, further mechanistic understanding of the underlying processes was acquired by non-targeted metabolomic profiling of a CHO cell line expressing a mAb cultured in four distinct process formats. Univariate analysis of intra- and extracellular metabolite and temporal glycosylation profiles provided insights in various pathways. The numerous of parameters were the main driver to carry out principal component analysis, and then, using the methodology of partial-least-square (PLS) projection on latent structures, a multivariate model was built to correlate the extracellular data with the distinct glycosylation profiles. The PLS observation model proved to be reliable and showed its great benefit for glycan pattern control in routine manufacturing, especially at large scale. Rather than relying on post-production interpretation of glycosylation results, glycosylation can be predicted in real-time based on the extracellular metabolite levels in the bioreactor. Finally, for the bioactivity assessment of the glycan differences between the biosimilar and the reference medicinal product (RMP), the health agencies may ask for in the drug registration process, extended ranges of glycan variants need to be generated so that the in vitro assays pick up the changes. The developed glycosylation modulator library enabled the generation of extreme glycosylation variants, including high mannose, afucosylated, galactosylated as well as sialic acid species of both a mAb and an antibody fusion molecule with three N-glycosylation sites. Moreover, to create increased variety, enzymatic glycoengineering was explored for galactosylation and sialylation. The glyco variants induced significant responses in the respective in vitro biological activity assays. The data of this work highlight the immense potential of cell culture medium optimization to adjust product quality. Medium and feed supplementation of a variety of compounds resulted in reproducible and important changes of the product quality profile of both mAbs and a fusion antibody. In addition to the intermediate modulation ranges that largely met the requirements for new-biological-entity and biosimilar development, medium supplementation even enabled quick and straightforward generation of extreme glycan variants suitable for biological activity testing.},
  subject      = {Zellkultur},
  language  = {en}
}
@inproceedings{OPUS4-14713,
  title     = {Research Network on Methodology for the Analysis of Social Interaction. Proceedings of the ninth meeting of MASI.},
  editor    = {Brill, Michael and Jonsson, Gudberg and Schwab, Frank},
  isbn      = {978-3-945459-16-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147135},
  year      = {2017},
  abstract  = {T-pattern analysis supports studies of various aspects of human or animal behavior as well as interaction between human subjects and animal or artificial agents. The following proceedings give an overiew on the application of T-pattern analysis in different research fields like media, gaming, human behaviour, social and organisational interaction as well as sports and health.},
  subject      = {Verhaltensmuster},
  language  = {en}
}
@phdthesis{Schmitt2017,
  author    = {Schmitt, Dominique},
  title     = {Initial characterization of mouse Syap1 in the nervous system: Search for interaction partners, effects of gene knockdown and knockout, and tissue distribution with focus on the adult brain},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147319},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {The synapse-associated protein of 47 kDa (Sap47) in Drosophila melanogaster is the founding member of a phylogenetically conserved protein family of hitherto unknown molecular function. Sap47 is localized throughout the entire neuropil of adult and larval brains and closely associated with glutamatergic presynaptic vesicles of larval motoneurons. Flies lacking the protein are viable and fertile and do not exhibit gross structural or marked behavioral deficiencies indicating that Sap47 is dispensable for basic synaptic function, or that its function is compensated by other related proteins. Syap1 - the mammalian homologue of Sap47 - was reported to play an essential role in Akt1 phosphorylation in various non-neuronal cells by promoting the association of mTORC2 with Akt1 which is critical for the downstream signaling cascade for adipogenesis. The function of Syap1 in the vertebrate nervous system, however, is unknown so far. The present study provides a first description of the subcellular localization of mouse Syap1 in cultured motoneurons as well as in selected structures of the adult mouse nervous system and reports initial functional experiments. Preceding all descriptive experiments, commercially available Syap1 antibodies were tested for their specificity and suitability for this study. One antibody raised against the human protein was found to recognize specifically both the human and murine Syap1 protein, providing an indispensable tool for biochemical, immunocytochemical and immunohistochemical studies. In the course of this work, a Syap1 knockout mouse was established and investigated. These mice are viable and fertile and do not show obvious changes in morphology or phenotype. As observed for Sap47 in flies, Syap1 is widely distributed in the synaptic neuropil, particularly in regions rich in glutamatergic synapses but it was also detected at perinuclear Golgi-associated sites in certain groups of neuronal somata. In motoneurons the protein is especially observed in similar perinuclear structures, partially overlapping with Golgi markers and in axons, dendrites and axonal growth cones. Biochemical and immunohistochemical analyses showed widespread Syap1 expression in the central nervous system with regionally distinct distribution patterns in cerebellum, hippocampus or olfactory bulb. Besides its expression in neurons, Syap1 is also detected in non-neuronal tissue e.g. liver, kidney and muscle tissue. In contrast, non-neuronal cells in the brain lack the typical perinuclear accumulation. First functional studies with cultured primary motoneurons on developmental, structural and functional aspects reveal no influence of Syap1 depletion on survival and morphological features such as axon length or dendritic length. Contrary to expectations, in neuronal tissues or cultured motoneurons a reduction of Akt phosphorylation at Ser473 or Thr308 was not detected after Syap1 knockdown or knockout.},
  subject      = {Synapse},
  language  = {en}
}
@phdthesis{Benkert2017,
  author    = {Benkert, Andreas},
  title     = {Soft x-ray spectroscopic study of methanol and glycine peptides in different physical environments},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147111},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Ionenspezifische Effekte treten in einer Vielzahl von w{\"a}ssrigen L{\"o}sungen aus Elektrolyten und gr{\"o}ßeren Molek{\"u}len wie Peptiden auf. Die Ionen bewirken dabei {\"A}nderungen in Eigenschaften wie z.B. der Viskosit{\"a}t, den Aktivit{\"a}ten von Enzymen, der Stabilit{\"a}t von Proteinen und deren Ein- bzw. Aussalzverhalten. Typischerweise wird die ionenabh{\"a}ngige Auspr{\"a}gung derartiger Effekte mithilfe der Hofmeister-Serie beschrieben, die urspr{\"u}nglich Ionen nach ihrer F{\"a}higkeit ordnete, die L{\"o}slichkeit von H{\"u}hnereiweis in Wasser zu steigern oder zu unterdr{\"u}cken. Die empirische Abfolge der Ionen in der Hofmeister-Serie kann jedoch bis heute nicht zweifelsfrei erkl{\"a}rt werden. Trotz weitreichender Bem{\"u}hungen, ein molekulares Verst{\"a}ndnis dieses Ph{\"a}nomens zu schaffen, konnte bisher keine Einigung {\"u}ber die zugrundeliegenden Mechanismen und die genauere Bestimmung und Lokalisierung der Wechselwirkung erzielt werden. Die resonante inelastische Weichr{\"o}ntgenstreuung (RIXS) kombiniert die beiden Methoden der R{\"o}ntgenemissions- (XES) und R{\"o}ntgenabsorptionsspektroskopie (XAS). So k{\"o}nnen mit RIXS Informationen sowohl {\"u}ber die besetzten als auch die unbesetzten elektronischen Zust{\"a}nde gesammelt und zu einem umfassenden Bild der elektronischen Struktur des Systems verkn{\"u}pft werden, was diese Methode zu einem vielversprechenden Werkzeug macht, etwas mehr Licht auf die Thematik zu werfen. Die in dieser Arbeit pr{\"a}sentierten Ergebnisse zielen deshalb darauf ab, ein verbessertes Verst{\"a}ndnis der Wechselwirkungen zwischen Salzen und Peptiden in w{\"a}ssriger L{\"o}sung zu schaffen. Hierf{\"u}r wird systematisch der Einfluss verschiedenster physikalischer Umgebungen auf die elektronische Struktur von kleinen Molek{\"u}len (Methanol und von Glycin abgeleitete Peptide) mittels Weichr{\"o}ntgenspektroskopie, unterst{\"u}tzt durch Dichtefunktionaltheorie (DFT) Rechnungen, untersucht. In einem ersten Schritt werden isolierte Molek{\"u}le ohne jeglicheWechselwirkung zu ihrer unmittelbaren Umgebung anhand von Methanol in der Gasphase als Modelsystem untersucht. Hierbei wird insbesondere der lokale und elementspezifische Charakter von RIXS demonstriert und die lokale elektronische Struktur von Methanols Hydroxyl- und Methylgruppe untersucht. Mithilfe von DFT-Rechnungen werden die beobachteten Emissionslinien in den XES-Spektren der Emission bestimmter Molek{\"u}lorbitale zugeordnet und deren relative Emissionsintensit{\"a}ten erl{\"a}utert. F{\"u}r eine resonante Anregung der ersten Resonanz an der Sauerstoff-K-Absorptionskante werden starke Isotopeneffekte beobachtet, die durch dynamische Prozesse an der Hydroxylgruppe erkl{\"a}rt werden k{\"o}nnen. Dies dient als hervorragendes Beispiel f{\"u}r m{\"o}gliche Auswirkungen, die eine lokale {\"A}nderung in der Geometrie oder Symmetrie des Molek{\"u}ls auf dessen elektronische Struktur haben kann. Im weiteren Verlauf dieser Arbeit wird das untersuchte Probensystem um die Aminos{\"a}ure Glycin und deren kleinste Peptide Diglycin und Triglycin, vorerst in ihrer kristallinen Form als Festk{\"o}rper, erweitert. Mithilfe von RIXS-Karten der Stickstoff- und Sauerstoff-K-Absorptionskanten wird erneut, unterst{\"u}tzt durch DFT-Rechnungen, ein umfassendes Bild der elektronischen Struktur der Molek{\"u}le gezeichnet. {\"A}hnlich zum Fall von Methanol werden die Emissionsspektren an der Stickstoff-K-Kante stark von dynamischen Prozessen an der protonierten Aminogruppe der Molek{\"u}le beeinflusst. Zudem wird gezeigt, dass RIXS gezielt dazu verwendet werden kann, das Stickstoffatom in der Peptidbindung anzuregen und die elektronische Struktur in dessen lokaler Umgebung zu untersuchen. Desweiteren wird ein einfaches Baukastenprinzip f{\"u}r XES-Spektren dazu genutzt, die spektralen Anteile der Emission aus {\"U}berg{\"a}ngen an den beiden Stickstoffatomen in Diglycin zu isolieren. In w{\"a}ssriger L{\"o}sung kann eine leichte Ver{\"a}nderung der elektronischen Struktur der Molek{\"u}le durch die Wechselwirkung mit benachbarten Wassermolek{\"u}len, vermutlich an den geladenen funktionellen Gruppen, beobachtet werden. Die Auswirkungen auf die XES-Spektren sind jedoch eher gering. Deutlich gr{\"o}ßere Ver{\"a}nderungen werden beobachtet, wenn man den Protonierungszustand der Molek{\"u}le {\"u}ber den pH-Wert der L{\"o}sung manipuliert. Sowohl die Protonierung der Carboxylgruppe f{\"u}r kleine pH-Werte als auch die Deprotonierung der Aminogruppe in basischer L{\"o}sung f{\"u}hren zu starken Ver{\"a}nderungen in den RIXS-Karten. In einer umfangreichen Untersuchung der XES-Spektren von Glycin als Funktion des pH-Wertes wird gezeigt, dass sich die {\"A}nderungen jedoch nicht nur {\"o}rtlich begrenzt auf die Umgebung der manipulierten funktionellen Gruppe, sondern auch auf die elektronische Struktur in weiter entfernten Bereichen des Molek{\"u}ls auswirken. Als Beispiel f{\"u}r Systeme in denen Hofmeister-Effekte beobachtet werden, werden zu guter Letzt gemischte w{\"a}ssrige L{\"o}sungen aus Diglycin und verschiedenen Salzen untersucht. Um den Einfluss verschiedener Kationen auf die elektronische Struktur der Diglycin Molek{\"u}le zu erfassen wird eine Reihe unterschiedlicher Chloride verwendet, wohingegen eine Reihe von Kaliumsalzen f{\"u}r die Untersuchung verschiedener Anionen herangezogen wird. In beiden F{\"a}llen werden ionenspezifische Auswirkungen auf die XES-Spektren von Diglycin beobachtet, die qualitativ der Sortierung innerhalb der Hofmeister-Serie folgen. Die beobachteten {\"A}nderungen deuten dabei darauf hin, dass Kationen unterschiedlich stark mit dem Sauerstoff in der Peptidbindung und dessen unmittelbarer Umgebung wechselwirken, wohingegen Anionen eine gesteigerte Affinit{\"a}t zur Aminogruppe von Diglycin aufweisen.},
  subject      = {Methanol},
  language  = {en}
}
@phdthesis{Rygielski2017,
  author    = {Rygielski, Piotr},
  title     = {Flexible Modeling of Data Center Networks for Capacity Management},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146235},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Nowadays, data centers are becoming increasingly dynamic due to the common adoption of virtualization technologies. Systems can scale their capacity on demand by growing and shrinking their resources dynamically based on the current load. However, the complexity and performance of modern data centers is influenced not only by the software architecture, middleware, and computing resources, but also by network virtualization, network protocols, network services, and configuration. The field of network virtualization is not as mature as server virtualization and there are multiple competing approaches and technologies. Performance modeling and prediction techniques provide a powerful tool to analyze the performance of modern data centers. However, given the wide variety of network virtualization approaches, no common approach exists for modeling and evaluating the performance of virtualized networks. The performance community has proposed multiple formalisms and models for evaluating the performance of infrastructures based on different network virtualization technologies. The existing performance models can be divided into two main categories: coarse-grained analytical models and highly-detailed simulation models. Analytical performance models are normally defined at a high level of abstraction and thus they abstract many details of the real network and therefore have limited predictive power. On the other hand, simulation models are normally focused on a selected networking technology and take into account many specific performance influencing factors, resulting in detailed models that are tightly bound to a given technology, infrastructure setup, or to a given protocol stack. Existing models are inflexible, that means, they provide a single solution method without providing means for the user to influence the solution accuracy and solution overhead. To allow for flexibility in the performance prediction, the user is required to build multiple different performance models obtaining multiple performance predictions. Each performance prediction may then have different focus, different performance metrics, prediction accuracy, and solving time. The goal of this thesis is to develop a modeling approach that does not require the user to have experience in any of the applied performance modeling formalisms. The approach offers the flexibility in the modeling and analysis by balancing between: (a) generic character and low overhead of coarse-grained analytical models, and (b) the more detailed simulation models with higher prediction accuracy. The contributions of this thesis intersect with technologies and research areas, such as: software engineering, model-driven software development, domain-specific modeling, performance modeling and prediction, networking and data center networks, network virtualization, Software-Defined Networking (SDN), Network Function Virtualization (NFV). The main contributions of this thesis compose the Descartes Network Infrastructure (DNI) approach and include: • Novel modeling abstractions for virtualized network infrastructures. This includes two meta-models that define modeling languages for modeling data center network performance. The DNI and miniDNI meta-models provide means for representing network infrastructures at two different abstraction levels. Regardless of which variant of the DNI meta-model is used, the modeling language provides generic modeling elements allowing to describe the majority of existing and future network technologies, while at the same time abstracting factors that have low influence on the overall performance. I focus on SDN and NFV as examples of modern virtualization technologies. • Network deployment meta-model—an interface between DNI and other meta- models that allows to define mapping between DNI and other descriptive models. The integration with other domain-specific models allows capturing behaviors that are not reflected in the DNI model, for example, software bottlenecks, server virtualization, and middleware overheads. • Flexible model solving with model transformations. The transformations enable solving a DNI model by transforming it into a predictive model. The model transformations vary in size and complexity depending on the amount of data abstracted in the transformation process and provided to the solver. In this thesis, I contribute six transformations that transform DNI models into various predictive models based on the following modeling formalisms: (a) OMNeT++ simulation, (b) Queueing Petri Nets (QPNs), (c) Layered Queueing Networks (LQNs). For each of these formalisms, multiple predictive models are generated (e.g., models with different level of detail): (a) two for OMNeT++, (b) two for QPNs, (c) two for LQNs. Some predictive models can be solved using multiple alternative solvers resulting in up to ten different automated solving methods for a single DNI model. • A model extraction method that supports the modeler in the modeling process by automatically prefilling the DNI model with the network traffic data. The contributed traffic profile abstraction and optimization method provides a trade-off by balancing between the size and the level of detail of the extracted profiles. • A method for selecting feasible solving methods for a DNI model. The method proposes a set of solvers based on trade-off analysis characterizing each transformation with respect to various parameters such as its specific limitations, expected prediction accuracy, expected run-time, required resources in terms of CPU and memory consumption, and scalability. • An evaluation of the approach in the context of two realistic systems. I evaluate the approach with focus on such factors like: prediction of network capacity and interface throughput, applicability, flexibility in trading-off between prediction accuracy and solving time. Despite not focusing on the maximization of the prediction accuracy, I demonstrate that in the majority of cases, the prediction error is low—up to 20\% for uncalibrated models and up to 10\% for calibrated models depending on the solving technique. In summary, this thesis presents the first approach to flexible run-time performance prediction in data center networks, including network based on SDN. It provides ability to flexibly balance between performance prediction accuracy and solving overhead. The approach provides the following key benefits: • It is possible to predict the impact of changes in the data center network on the performance. The changes include: changes in network topology, hardware configuration, traffic load, and applications deployment. • DNI can successfully model and predict the performance of multiple different of network infrastructures including proactive SDN scenarios. • The prediction process is flexible, that is, it provides balance between the granularity of the predictive models and the solving time. The decreased prediction accuracy is usually rewarded with savings of the solving time and consumption of resources required for solving. • The users are enabled to conduct performance analysis using multiple different prediction methods without requiring the expertise and experience in each of the modeling formalisms. The components of the DNI approach can be also applied to scenarios that are not considered in this thesis. The approach is generalizable and applicable for the following examples: (a) networks outside of data centers may be analyzed with DNI as long as the background traffic profile is known; (b) uncalibrated DNI models may serve as a basis for design-time performance analysis; (c) the method for extracting and compacting of traffic profiles may be used for other, non-network workloads as well.},
  subject      = {Modellierung},
  language  = {en}
}
@unpublished{ArrowsmithBraunschweigStennett2017,
  author    = {Arrowsmith, Merle and Braunschweig, Holger and Stennett, Tom},
  title     = {Formation and Reactivity of Electron-Precise B-B Single and Multiple Bonds},
  series = {Angewandte Chemie, International Edition},
  volume    = {56},
  journal   = {Angewandte Chemie, International Edition},
  number    = {1},
  doi       = {10.1002/anie.201610072},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145631},
  pages     = {96-115},
  year      = {2017},
  abstract  = {Recent years have seen rapid advances in the chemistry of small molecules containing electron-precise boron-boron bonds. This review provides an overview of the latest methods for the controlled synthesis of B-B single and multiple bonds as well as the ever-expanding range of reactivity displayed by the latter.},
  language  = {en}
}
@phdthesis{Reimer2017,
  author    = {Reimer, Anastasija},
  title     = {Search for novel antimicrobials against \(Neisseria\) \(gonorrhoeae\) and \(Chlamydia\) \(trachomatis\)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143168},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {The obligate human pathogen Neisseria gonorrhoeae is responsible for the widespread sexually transmitted disease gonorrhoea, which in rare cases also leads to the development of disseminated gonococcal infection (DGI). DGI is mediated by PorBIA-expressing bacteria that invade host cells under low phosphate condition by interaction with the scavenger receptor-1 (SREC-I) expressed on the surface of endothelial cells. The interaction of PorBIA and SREC-I was analysed using different in vitro approaches, including surface plasmon resonance experiments that revealed a direct phosphate-independent high affinity interaction of SREC-I to PorBIA. However, the same binding affinity was also found for the other allele PorBIB, which indicates unspecific binding and suggests that the applied methods were unsuitable for this interaction analysis. Since N. gonorrhoeae was recently classified as a "super-bug" due to a rising number of antibiotic-resistant strains, this study aimed to discover inhibitors against the PorBIA-mediated invasion of N. gonorrhoeae. Additionally, inhibitors were searched against the human pathogen Chlamydia trachomatis, which causes sexually transmitted infections as well as infections of the upper inner eyelid. 68 compounds, including plant-derived small molecules, extracts or pure compounds of marine sponges or sponge-associated bacteria and pipecolic acid derivatives, were screened using an automated microscopy based approach. No active substances against N. gonorrhoeae could be identified, while seven highly antichlamydial compounds were detected. The pipecolic acid derivatives were synthesized as potential inhibitors of the virulence-associated "macrophage infectivity potentiator" (MIP), which exhibits a peptidyl prolyl cis-trans isomerase (PPIase) enzyme activity. This study investigated the role of C. trachomatis and N. gonorrhoeae MIP during infection. The two inhibitors PipN3 and PipN4 decreased the PPIase activity of recombinant chlamydial and neisserial MIP in a dose-dependent manner. Both compounds affected the chlamydial growth and development in epithelial cells. Furthermore, this work demonstrated the contribution of MIP to a prolonged survival of N. gonorrhoeae in the presence of neutrophils, which was significantly reduced in the presence of PipN3 and PipN4. SF2446A2 was one of the compounds that had a severe effect on the growth and development of C. trachomatis. The analysis of the mode of action of SF2446A2 revealed an inhibitory effect of the compound on the mitochondrial respiration and mitochondrial ATP production of the host cell. However, the chlamydial development was independent of proper functional mitochondria, which excluded the connection of the antichlamydial properties of SF2446A2 with its inhibition of the respiratory chain. Only the depletion of cellular ATP by blocking glycolysis and mitochondrial respiratory chain inhibited the chlamydial growth. A direct effect of SF2446A2 on C. trachomatis was assumed, since the growth of the bacteria N. gonorrhoeae and Staphylococcus aureus was also affected by the compound. In summary, this study identified the severe antichlamydial activity of plant-derived naphthoquinones and the compounds derived from marine sponges or sponge-associated bacteria SF2446A2, ageloline A and gelliusterol E. Furthermore, the work points out the importance of the MIP proteins during infection and presents pipecolic acid derivatives as novel antimicrobials against N. gonorrhoeae and C. trachomatis.},
  subject      = {Neisseria gonorrhoeae},
  language  = {en}
}
@phdthesis{Gaviraghi2017,
  author    = {Gaviraghi, Beatrice},
  title     = {Theoretical and numerical analysis of Fokker-Planck optimal control problems for jump-diffusion processes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145645},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {The topic of this thesis is the theoretical and numerical analysis of optimal control problems, whose differential constraints are given by Fokker-Planck models related to jump-diffusion processes. We tackle the issue of controlling a stochastic process by formulating a deterministic optimization problem. The key idea of our approach is to focus on the probability density function of the process, whose time evolution is modeled by the Fokker-Planck equation. Our control framework is advantageous since it allows to model the action of the control over the entire range of the process, whose statistics are characterized by the shape of its probability density function. We first investigate jump-diffusion processes, illustrating their main properties. We define stochastic initial-value problems and present results on the existence and uniqueness of their solutions. We then discuss how numerical solutions of stochastic problems are computed, focusing on the Euler-Maruyama method. We put our attention to jump-diffusion models with time- and space-dependent coefficients and jumps given by a compound Poisson process. We derive the related Fokker-Planck equations, which take the form of partial integro-differential equations. Their differential term is governed by a parabolic operator, while the nonlocal integral operator is due to the presence of the jumps. The derivation is carried out in two cases. On the one hand, we consider a process with unbounded range. On the other hand, we confine the dynamic of the sample paths to a bounded domain, and thus the behavior of the process in proximity of the boundaries has to be specified. Throughout this thesis, we set the barriers of the domain to be reflecting. The Fokker-Planck equation, endowed with initial and boundary conditions, gives rise to Fokker-Planck problems. Their solvability is discussed in suitable functional spaces. The properties of their solutions are examined, namely their regularity, positivity and probability mass conservation. Since closed-form solutions to Fokker-Planck problems are usually not available, one has to resort to numerical methods. The first main achievement of this thesis is the definition and analysis of conservative and positive-preserving numerical methods for Fokker-Planck problems. Our SIMEX1 and SIMEX2 (Splitting-Implicit-Explicit) schemes are defined within the framework given by the method of lines. The differential operator is discretized by a finite volume scheme given by the Chang-Cooper method, while the integral operator is approximated by a mid-point rule. This leads to a large system of ordinary differential equations, that we approximate with the Strang-Marchuk splitting method. This technique decomposes the original problem in a sequence of different subproblems with simpler structure, which are separately solved and linked to each other through initial conditions and final solutions. After performing the splitting step, we carry out the time integration with first- and second-order time-differencing methods. These steps give rise to the SIMEX1 and SIMEX2 methods, respectively. A full convergence and stability analysis of our schemes is included. Moreover, we are able to prove that the positivity and the mass conservation of the solution to Fokker-Planck problems are satisfied at the discrete level by the numerical solutions computed with the SIMEX schemes. The second main achievement of this thesis is the theoretical analysis and the numerical solution of optimal control problems governed by Fokker-Planck models. The field of optimal control deals with finding control functions in such a way that given cost functionals are minimized. Our framework aims at the minimization of the difference between a known sequence of values and the first moment of a jump-diffusion process; therefore, this formulation can also be considered as a parameter estimation problem for stochastic processes. Two cases are discussed, in which the form of the cost functional is continuous-in-time and discrete-in-time, respectively. The control variable enters the state equation as a coefficient of the Fokker-Planck partial integro-differential operator. We also include in the cost functional a \$L^1\$-penalization term, which enhances the sparsity of the solution. Therefore, the resulting optimization problem is nonconvex and nonsmooth. We derive the first-order optimality systems satisfied by the optimal solution. The computation of the optimal solution is carried out by means of proximal iterative schemes in an infinite-dimensional framework.},
  subject      = {Fokker-Planck-Gleichung},
  language  = {en}
}