@phdthesis{CruzdeCasas2024,
  author    = {Cruz de Casas, Paulina},
  title     = {Sphingolipids as modulators of T cell function},
  doi       = {10.25972/OPUS-35969},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359698},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The immune system is responsible for the preservation of homeostasis whenever a given organism is exposed to distinct kinds of perturbations. Given the complexity of certain organisms like mammals, and the diverse types of challenges that they encounter (e.g. infection or disease), the immune system evolved to harbor a great variety of distinct immune cell populations with specialized functions. For instance, the family of T cells is sub-divided into conventional (Tconv) and unconventional T cells (UTCs). Tconv form part of the adaptive arm of the immune system and are comprised of αβ CD4+ or CD8+ cells that differentiate from na{\"i}ve to effector and memory populations upon activation and are essential during infection and cancer. Furthermore, UTCs, which include γδ T cells, NKT and MAIT, are involved in innate and adaptive immune responses, due to their dual mode of activation, through cytokines (innate-like) or TCR (adaptive), and function. Despite our understanding of the basic functions of T cells in several contexts, a great number of open questions related to their basic biology remain. For instance, the mechanism behind the differentiation of na{\"i}ve CD4+ and CD8+ T cells into effector and memory populations is not fully understood. Moreover, the exact function and relevance of distinct UTC subpopulations in a physiological context have not been fully clarified. Here, we investigated the factors mediating na{\"i}ve CD8+ T cell differentiation into effector and memory cells. By using flow cytometry, mass spectrometry, enzymatic assays, and transgenic mouse models, we found that the membrane bound enzyme sphingomyelin-phosphodiesterase acid-like 3b (Smpdl3b) is crucial for the maintenance of memory CD8+ T cells. Our data show that the absence of Smpdl3b leads to diminished CD8+ T cell memory, and a loss of stem-like memory populations due to an aggravated contraction. Our scRNA-seq data suggest that Smpdl3b could be involved in clathrinmediated endocytosis through modulation of Huntingtin interacting protein 1 (Hip1) levels, likely regulating TCR-independent signaling events. Furthermore, in this study we explored the role of UTCs in lymph node-specific immune responses. By using transgenic mouse models for photolabeling, lymph node transplantation models, infection models and flow cytometry, we demonstrate that S1P regulates the migration of tissue-derived UTC from tissues to draining lymph nodes, resulting in heterogeneous immune responses mounted by lymph nodes draining different tissues. Moreover, our unbiased scRNAseq and single lineage-deficient mouse models analysis revealed that all UTC lineages (γδ T cells, NKT and MAIT) are organized in functional units, based on transcriptional homogeneity, shared microanatomical location and migratory behavior, and numerical and functional redundancy. Taken together, our studies describe additional cell intrinsic (Smpdl3b) and extrinsic (S1Pmediated migration) functions of sphingolipid metabolism modulating T cell biology. We propose the S1P/S1PR1/5 signaling axis as the potential survival pathway for Smpdl3b+ memory CD8+ T cells and UTCs, mainly in lymph nodes. Possibly, Smpdl3b regulates S1P/S1PR signaling by balancing ligandreceptor endocytosis, while UTCs migrate to lymph nodes during homeostasis to be exposed to specific levels of S1P that assure their maintenance. Our results are clinically relevant, since several drugs modulating the S1P/S1PR signaling axis or the levels of Smpdl3b are currently used to treat human diseases, such as multiple sclerosis and B cell-mediated diseases. We hope that our discoveries will inspire future studies focusing on sphingolipid metabolism in immune cell biology.},
  subject      = {T-Lymphozyt},
  language  = {en}
}
@phdthesis{Amini2024,
  author    = {Amini, Emad},
  title     = {How central and peripheral clocks and the neuroendocrine system interact to time eclosion behavior in \(Drosophila\) \(melanogaster\)},
  doi       = {10.25972/OPUS-36130},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361309},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {To grow larger, insects must shed their old rigid exoskeleton and replace it with a new one. This process is called molting and the motor behavior that sheds the old cuticle is called ecdysis. Holometabolic insects have pupal stages in between their larval and adult forms, during which they perform metamorphosis. The pupal stage ends with eclosion, i.e., the emergence of the adult from the pupal shell. Insects typically eclose at a specific time during the day, likely when abiotic conditions are at their optimum. A newly eclosed insect is fragile and needs time to harden its exoskeleton. Hence, eclosion is regulated by sophisticated developmental and circadian timing mechanisms. In Drosophila melanogaster, eclosion is limited to a daily time window in the morning, regarded as the "eclosion gate". In a population of laboratory flies entrained by light/dark cycles, most of the flies eclose around lights on. This rhythmic eclosion pattern is controlled by the circadian clock and persists even under constant conditions. Developmental timing is under the control of complex hormonal signaling, including the steroid ecdysone, insulin-like peptides, and prothoracicotropic hormone (PTTH). The interactions of the central circadian clock in the brain and a peripheral clock in the prothoracic gland (PG) that produces ecdysone are important for the circadian timing of eclosion. These two clocks are connected by a bilateral pair of peptidergic PTTH neurons (PTTHn) that project to the PG. Before each molt, the ecdysone level rises and then falls shortly before ecdysis. The falling ecdysone level must fall below a certain threshold value for the eclosion gate to open. The activity of PTTHn is inhibited by short neuropeptide F (sNPF) from the small ventrolateral neurons (sLNvs) and inhibition is thought to lead to a decrease in ecdysone production. The general aim of this thesis is to further the understanding of how the circadian clock and neuroendocrinal pathways are coordinated to drive eclosion rhythmicity and to identify when these endocrinal signaling pathways are active. In Chapter I, a series of conditional PTTHn silencing-based behavioral assays, combined with neuronal activity imaging techniques such as non-invasive ARG-Luc show that PTTH signaling is active and required shortly before eclosion and may serve to phase-adjust the activity of the PG at the end of pupal development. Trans-synaptic anatomical stainings identified the sLNvs, dorsal neurons 1 (DN1), dorsal neurons 2 (DN2), and lateral posterior neurons (LPNs) clock neurons as directly upstream of the PTTHn. Eclosion motor behavior is initiated by Ecdysis triggering hormone (ETH) which activates a pair of ventromedial (Vm) neurons to release eclosion hormone (EH) which positively feeds back to the source of ETH, the endocrine Inka cells. In Chapter II trans-synaptic tracing showed that most clock neurons provide input to the Vm and non-canonical EH neurons. Hence, clock can potentially influence the ETH/EH feedback loop. The activity profile of the Inka cells and Vm neurons before eclosion is described. Vm and Inka cells are active around seven hours before eclosion. Interestingly, all EH neurons appear to be exclusively peptidergic. In Chapter III, using chemoconnectomics, PTTHns were found to express receptors for sNPF, allatostatin A (AstA), allatostatin C (AstC), and myosuppressin (Ms), while EH neurons expressed only Ms and AstA receptors. Eclosion assays of flies with impaired AstA, AstC, or Ms signaling do not show arrhythmicity under constant conditions. However, optogenetic activation of the AstA neurons strongly suppresses eclosion. Chapter IV focuses on peripheral ventral' Tracheal dendrite (v'Td) and class IV dendritic arborization (C4da) neurons. The C4da neurons mediate larval light avoidance through endocrine PTTH signaling. The v'Td neurons mainly receive O2/CO2 input from the trachea and are upstream of Vm neurons but are not required for eclosion rhythmicity. Conditional ablation of the C4da neurons or torso (receptor of PTTH) knock-out in the C4da neurons impaired eclosion rhythmicity. Six to seven hours before eclosion, PTTHn, C4da, and Vm neurons are active based on ARG-Luc imaging. Thus, C4da neurons may indirectly connect the PTTHn to the Vm neurons. In summary, this thesis advances our knowledge of the temporal activity and role of PTTH signaling during pupal development and rhythmic eclosion. It further provides a comprehensive characterization of the synaptic and peptidergic inputs from clock neurons to PTTHn and EH neurons. AstA, AstC, and Ms are identified as potential modulators of eclosion circuits and suggest an indirect effect of PTTH signaling on EH signaling via the peripheral sensory C4da neurons.},
  subject      = {Neuroendokrines System},
  language  = {en}
}
@phdthesis{Roger2024,
  author    = {Roger, Chantal},
  title     = {Photophysics and Spin Chemistry of Triptycene Bridge Donor-Acceptor-Triads},
  doi       = {10.25972/OPUS-36303},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363031},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The goal of this thesis was to investigate the influence of rotational restriction between individual parts and of the varying electron density in the bridging unit of D B A systems on the exchange interaction 2J, and thus the electronic coupling between a donor state and an acceptor state. A better understanding of how to influence the underlaying spin dynamics in such donor acceptor systems can open up the door to new technologies, such as modern molecular electronics or optoelectronic devices. Therefore, three series of molecules consisting of a TAA electron donor, a TTC or ATC bridging unit and a PDI electron acceptor were studied. To investigate the influence of rotational restriction on 2J and the electronic coupling, a series of four rotationally hindered triads (chapter 6) was synthesised. The dihedral angle between the TAA and the TTC as well as between the TTC and the PDI was restricted by ortho methyl groups at the phenylene linkers of the connecting ends to the TTC bridge, producing a twist around the linking single bond which minimises the π overlap. The triads exhibit varying numbers of ortho methyl groups and therefore different degrees of rotational restriction. In order to shine light on the influence of varying electron density on 2J and the electronic coupling, a series of four substituted triptycene triads (chapter 7) was synthesised. The electron density in the TTC bridging unit was varied by electron donating and electron withdrawing groups in 12,13 position of the TTC bridging unit and thus varying its HOMO/LUMO energy. The last series of two anthracene bridge triads (chapter 8) connected both approaches by restricting the rotation with ortho methyl groups and simultaneously by varying the bridge energies. In order to obtain the electronic properties, steady state absorption and emission spectra of all triads were investigated (chapter 4). Here, all triads show spectral features associated with the separate absorption bands of TAA and the PDI moiety. The reduced QYs, compared to the unsubstituted PDI acceptor, indicate a non radiative quenching mechanism in all triads. The CV data (chapter 5) were used to calculate the energies of possible CSSs and those results were used to assign the CR dynamics into the different Marcus regions. fs TA measurements reveal that all triads form a CSS upon excitation of the PDI moiety. The lifetimes of the involved states and the rate constants were determined by global exponential fits and global target analysis. The CR dynamics upon depopulation of the CSSs were investigated using external magnetic field dependent ns TA spectroscopy. The ns TA maps show that all triads recombine via CRT pathway populating the local 3PDI state in toluene and provided the respective lifetimes. The approximate QYs of triplet formation were determined using actinometry. The magnetic field dependent ns TA data reveal the exchange interaction 2J between singlet and triplet CSS for each triad. Those magnetic field dependent ns TA data in toluene were furthermore treated using a quantum mechanical simulation (done by U.E. Steiner) to extract the rate constants kT and kS for CRT and CRS, respectively. However, the error margins of kS were rather wide. Finally, the electronic couplings between the donor and the acceptor states were obtained by combining the aforementioned experimental results of the rate constants and applying the Bixon Jortner theoretical description of diabatic ET and Andersons perturbative theory of the exchange coupling. Therefore, the experimentally determined values of 2J and the calculated values of kCS and kT were used. The rate constant kS was calculated based on the electronic coupling V1CSS 1S0. The rotationally hindered triads (chapter 6) show a strong influence of the degree of rotational restriction on the lifetimes and rate constants of the CS processes. The rate constants of CS are increasing with increasing rotational freedom. The magnetic field dependent decay data show that the exchange interactions increase with increasing rotational freedom. Based on the CR dynamics, the calculated electronic couplings of the ET processes reflect the same trend along the series. Here, only singlet couplings turned out to be strongly influenced while the triplet couplings are not. Therefore, this series shows that the ET dynamics of donor acceptor systems can strongly be influenced by restricting the rotational freedom. In the substituted triptycene triads (chapter 7), decreasing electron density in the bridging unit causes a decrease of the CS rate constants. The magnetic field dependent decay data show that with decreasing electron density in the bridge the exchange interaction decreases. The CR dynamics-based rate constants and the electronic couplings follow the same trend as the exchange interaction. This series shows that varying the HOMO/LUMO levels of the connecting bridge between donor and acceptor strongly influences the ET processes. In the anthracene bridge triads (chapter 8), the CS process is slow in both triads. The CR was fast in the anthracene triad and is slowed down in the methoxy substituted anthracene bridge triad. The increase of the exchange interaction with increasing electron density in the bridge was more pronounced than in the substituted triptycene triads. Thus, the variation of electron density in the bridge strongly influences the ET processes even though the rotation is restricted. In this thesis, it was shown that the influence of the rotational hindrance as well as the electron density in a connecting bridge have strong influence on all ET processes and the electronic coupling in donor acceptor systems. These approaches can therefore be used to modify magnetic properties of new materials.},
  subject      = {Rotation},
  language  = {en}
}
@phdthesis{Swain2024,
  author    = {Swain, Asim},
  title     = {Helically Twisted Graphene Nanoribbons: Bottom-up Stereospecific Synthesis and Characterization},
  doi       = {10.25972/OPUS-36016},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360164},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Over the past decade, substantial progress has been made in synthesizing atomically precise carbon nanostructures, with a focus on graphene nanoribbons (NRs) through advanced synthetic techniques. Despite these advancements, precise control over the stereochemistry of twisted NRs remains challenging. This thesis introduces a strategic approach to achieve absolute control over the single-handed helical conformation in a cove-edged NR, utilizing enantiopure [n]helicenes as a molecular wrench to intricately dictate the overall conformation of the NR. Enantiopure [7]helicenes were stitched to the terminal K-regions of a conjugated pyrene NR using a stereospecific and site-selective palladium(II)-catalyzed annulative π-extension (APEX) reaction, resulting in a helically twisted NR with an end-to-end twist of 171°, the second-largest twist reported so far in the literature for twistacenes. The helical end-to-end twist increases with each addition of benzene ring to the central acene core, suggesting that the extra strain induced by the terminal [7]helicenes maintains such a high level of twist. The quantum chemical calculations were conducted to investigate the impact of twisting on the conformational population. At room temperature, the central backbone of the nanoribbon adopts the twisted helicity opposite to that of the attached [7]helicene, constituting around 99\% of the molecular population. For instance, (P)-[7]helicenes produce a left-handed helical nanoribbon, while (M)-[7]helicenes produce a right-handed helical nanoribbon. In the presence of helicenes of opposite chirality, the nanoribbon adopts a waggling conformation. The helically twisted nanoribbons are conformationally robust, as variable temperature chiroptical measurements showed no change in CD and CPL spectra. The proposed strategy, involving the late-stage addition of [n]helicene units through the APEX reaction, appears promising for streamlining the synthesis of diverse cove edge NR variants with desired conformations. In addition to single-handed helically twisted nanoribbons, the symmetry-based functional properties of C2 and C1 symmetric pyrene-fused single and double [n]helicene compounds were studied. Owing to its higher structural rigidity, the C1 symmetric heptagonal ring-containing molecules exhibited exceptional configurational stability along with remarkable chiroptical properties compared to their C2 symmetric as well as pristine helicene congeners.},
  subject      = {Helicene},
  language  = {en}
}
@phdthesis{Glueck2024,
  author    = {Gl{\"u}ck, Valentina},
  title     = {Habitual avoidance in trait anxiety and anxiety disorders},
  doi       = {10.25972/OPUS-36022},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360227},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Maladaptive avoidance behaviors can contribute to the maintenance of fear, anxiety, and anxiety disorders. It has been proposed that, throughout anxiety disorder progression, extensively repeated avoidance may become a habit (i.e., habitual avoidance) instead of being controlled by internal threat-related goals (i.e., goal-directed avoidance). However, the process of the acquisition of habitual avoidance in anxiety disorders is not yet well understood. Accordingly, the current thesis aimed to investigate experimentally whether trait anxiety and anxiety disorders are associated with an increased shift from goal-directed to habitual avoidance. The aim of Study 1 was to develop an experimental operationalization of maladaptive habitual avoidance. To this end, we adapted a commonly used action control task, the outcome devaluation paradigm. In this task, habitual avoidance was operationalized as persistent responses after extensive training to avoid an unpleasant stimulus when the aversive outcome was devalued, i.e., when individuals knew the aversive outcome could not occur anymore. We included indicators for costly and low-cost habitual avoidance, whereby habitual avoidance was associated with a monetary cost, while low-cost habitual avoidance was not associated with monetary costs. In Experiment 1 of Study 1, a pronounced costly and non-costly outcome devaluation effect was observed. However, this result may have partly resulted from trial-and-error learning or a better-safe-than-sorry strategy since not instructions about the stimulus-response-outcome contingencies after the outcome devaluation procedure had been provided to the participants. In Experiment 2 of Study 1, instructions on these stimulus-response-outcome contingencies were included to prevent the potential confounders. As a result, we observed no indicators for costly habitual avoidance, but evidence for low-cost habitual avoidance, potentially because competing goal-directed responses could easily be implemented and inhibited costly habitual avoidance tendencies. In Study 2, the strength of habitual avoidance acquisition was compared between participants with and without anxiety disorders, using the experimental task of Experiment 1 in Study 1. The results indicated that costly and low-cost habitual avoidance was not more pronounced in participants with anxiety disorders than in the healthy control group. However, in an exploratory subgroup comparison, panic disorder predicted more substantial habitual avoidance acquisition than social anxiety disorder. In Study 3, we investigated whether trait anxiety as a risk factor for anxiety disorders is associated with a specific increased shift from goal-directed to habitual avoidance and approach. The task from the Experiment 1 of Study 1 was adapted to include parallel versions for operationalizing habitual avoidance and habitual approach responses. Using a within-subjects design, the individuals - pre-screened for high and low trait anxiety - took part in the approach and the avoidance outcome devaluation task version. The results suggested stronger non-costly habitual responses in more highly trait-anxious individuals independent of the task version, and suggested a tendency towards an impact of trait anxiety on costly habitual approach rather than on costly habitual avoidance. In summary, individuals with high trait anxiety or anxiety disorders did not develop habitual avoidance more readily than individuals with low trait anxiety or without anxiety disorders. Therefore, this thesis does not support the assumption that an increased tendency to acquire habitual avoidance contributes to persistent maladaptive avoidance in anxiety disorders. The thesis also contributes to the discourse on the validity of outcome devaluation studies in general by highlighting the impact of task features, such as the instructions after the outcome devaluation procedure or the task difficulty in the test phase, on the experimental results. Such validity issues may partly explain the heterogeneity of findings in research with the outcome devaluation paradigm. We suggest ways towards more valid operationalizations of habitual avoidance in future studies.},
  subject      = {Gewohnheit},
  language  = {en}
}
@phdthesis{Kagerer2024,
  author    = {Kagerer, Philipp Thomas},
  title     = {Two-Dimensional Ferromagnetism and Topology at the Surface of MnBi\(_2\)Te\(_4\) - Bi\(_2\)Te\(_3\) Heterostructures - MBE Growth, Magnetism and Electronic Properties},
  doi       = {10.25972/OPUS-36012},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360121},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In this thesis, a model system of a magnetic topological heterostructure is studied, namely a heterosystem consisting of a single ferromagnetic septuple-layer (SL) of \(MnBi_2Te_4\) on the surface of the three-dimensional topological insulator \(Bi_2Te_3\). Using MBE and developing a specialized experimental setup, the first part of this thesis deals with the growth of \(Bi_2Te_3\) and thin films of \(MnBi_2Te_4\) on \(BaF_2\)-substrates by the co-evaporation of its binary constituents. The structural analysis is conducted along several suitable probes such as X-ray diffraction (XRD, XRR), AFM and scanning tunnelling electron microscopy (STEM). It is furthermore found that the growth of a single septuple-layer of \(MnBi_2Te_4\) on the surface of \(Bi_2Te_3\) can be facilitated. By using X-ray absorption and circular magnetic dichroism (XAS, XMCD), the magnetic properties of \(MnBi_2Te_4\) are explored down to the monolayer limit. The layered nature of the vdW crystal and a strong uniaxial magnetocrystalline anisotropy establish stable out-of plane magnetic order at the surface of \(MnBi_2Te_4\), which is stable even down to the 2D limit. Pushing the material system to there, i.e. a single SL \(MnBi_2Te_4\) further allows to study the phase transition of this 2D ferromagnet and extract its critical behaviour with \(T_c \, = \, 14.89~k\) and \(\beta \, = \, 0.484\). Utilizing bulk crystals of the ferromagnetic \(Fe_3GeTe_2\) as substrate allows to influence, enhance and bias the magnetism in the single SL of \(MnBi_2Te_4\). By growing heterostructures of the type \(MnBi_2Te_4\) -- n layer \(Bi_2Te_3\) -- \(Fe_3GeTe_2\)for n between 0 and 2, it is shown, that a considerable magnetic coupling can be introduced between the \(MnBi_2Te_4\) top-layer and the substrate. Finally the interplay between topology and magnetism in the ferromagnetic extension is studied directly by angle-resolved photoemission spectroscopy. The heterostructure is found to host a linearly dispersing TSS at the centre of the Brillouin zone. Using low temperature and high-resolution ARPES a large magnetic gap opening of \(\sim\) 35 meV is found at the Dirac point of the TSS. By following its temperature evolution, it is apparent that the scaling behaviour coincides with the magnetic order parameter of the modified surface.},
  subject      = {Molekularstrahlepitaxie},
  language  = {en}
}
@phdthesis{Wussmann2024,
  author    = {Wußmann, Maximiliane},
  title     = {Humane organotypische 3D Modelle des Malignen Melanoms als in vitro Testsystem f{\"u}r die Bewertung der Wirksamkeit von anti-Tumor Therapeutika},
  doi       = {10.25972/OPUS-36100},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361005},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Das maligne Melanom, eine der seltensten, aber gleichzeitig auch die t{\"o}dlichste dermatologische Malignit{\"a}t, gekennzeichnet durch die Neigung zu einer fr{\"u}hen Metastasierung sowie die rasche Entwicklung von Therapieresistenzen, z{\"a}hlt zu den Tumorentit{\"a}ten mit dem h{\"o}chsten Anstieg der Inzidenz weltweit. Mausmodelle werden h{\"a}ufig verwendet, um die Melanomagenese zu erforschen und neue effektive therapeutische Strategien zu entwickeln, spiegeln die menschliche Physiologie allerdings nur unzureichend wider. In zweidimensionalen (2D) Zellkulturen mangelt es dagegen an wichtigen Komponenten der Mikroumgebung des Tumors und dem dreidimensionalen Gewebekontext. Um dieses Manko zu beheben und die Entwicklung von auf den Menschen {\"u}bertragbaren Tumormodellen in der onkologischen Forschung voranzutreiben, wurde als Alternative zu Zellkulturen und Tierversuchen humane organotypische dreidimensionale (3D) Melanom-Modelle als in vitro Testsystem f{\"u}r die Bewertung der Wirksamkeit von anti-Tumor Therapeutika entwickelt. Im Zuge dieser Arbeit konnte das in vitro Melanom-Modell entscheidend weiterentwickelt werden. So konnten Modelle unterschiedlichster Komplexit{\"a}t etabliert werden, wobei abh{\"a}ngig von der Fragestellung einfachere epidermale bis hin zu unterschiedlich komplexen Vollhautmodellen Anwendung finden. Durch Simulation der Tumor-Mikroumgebung eignen sich diese zur pr{\"a}klinischen Validierung neuer Tumor-Therapeutika, sowie der Erforschung pathologischer Vorg{\"a}nge, von der Tumor-Formierung bis zur Metastasierung. Zudem konnten erfolgreich unterschiedlichste humane Melanomzelllinien ins Modell integriert werden; dadurch, dass sich diese durch ihre Treibermutationen, die zur Krankheitsentstehung beitragen, unterscheiden, stellen sie unterschiedliche Anspr{\"u}che an potentielle therapeutische Angriffspunkte und erm{\"o}glichen das Widerspiegeln vieler Melanom-Subtypen im Modell. Ferner ist es m{\"o}glich, verschiedene Stadien der Tumor-Entwicklung {\"u}ber die Zugabe von Melanomzellen in Einzelsuspension bzw. von Melanom-Sph{\"a}roiden widerzuspiegeln. Es konnte f{\"u}r bestimmte Therapie-Ans{\"a}tze, wie zielgerichtete Therapien, z.B. die Gabe von sich in der Klinik im Einsatz befindlicher BRAF-/MEK-Inhibitoren, gezeigt werden, dass sich die etablierten Modelle hervorragend als pr{\"a}klinische Testsysteme zur Wirksamkeitsbewertung eignen. Zudem bieten sich einzigartige M{\"o}glichkeiten, um die Interaktion humaner Tumorzellen und gesunder Zellen in einem Gewebeverband zu untersuchen. Ferner konnten drei neue technische Analyse-Verfahren zur nicht-invasiven Detektion der Tumor- Pro- und Regression, Beurteilung der Wirksamkeit von potenziellen Anti-Tumor-Therapien sowie der Evaluierung des Tumor-Metabolismusses implementiert werden. Perspektivisch erm{\"o}glichen immun-kompetente Melanom-Modelle die Austestung neuer Immun- und Zelltherapien in einem voll humanen System; gleichzeitig leisten die etablierten Modelle einen signifikanten Beitrag zur Reduktion von Tierexperimenten.},
  subject      = {Melanom},
  language  = {de}
}
@phdthesis{Djakowski2024,
  author    = {Djakowski, Paul},
  title     = {Schulische politische Bildung in Deutschland und Polen. Eine kompetenzbasierte komparative Analyse der Leitf{\"a}cher f{\"u}r politische Bildung anhand von Stundentafeln und Curricula allgemeinbildender staatlicher Schulformen der Primarstufe sowie der Sekundarstufen I und II im Schuljahr 2019/20},
  publisher = {W{\"u}rzburg University Press},
  address   = {W{\"u}rzburg},
  isbn      = {978-3-95826-230-0},
  doi       = {10.25972/WUP-978-3-95826-231-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326799},
  school      = {W{\"u}rzburg University Press},
  pages     = {XXI, 593},
  year      = {2024},
  abstract  = {Politische Bildung {\"u}bt nicht nur einen großen Einfluss auf die zuk{\"u}nftige Konstellation des politischen Systems aus, sondern beeinflusst ebenfalls das soziale Miteinander pr{\"a}gend. Damit werden entscheidende Weichen f{\"u}r die Entwicklung der Gesellschaft, der Nation und des Staates gestellt. Im Zuge dieses Prozesses durchl{\"a}uft jeder junge B{\"u}rger einen politischen Bildungsweg an Schulen. Die Vorgaben dar{\"u}ber, wie schulische politische Bildung auszusehen hat und welche Kompetenzen Sch{\"u}ler in diesem Zusammenhang erwerben sollen, geben die Kultus- bzw. Bildungsministerien in Curricula vor, verbindlich f{\"u}r alle Lehrer. Durch eine komparative Analyse der Curricula kann damit eindeutig die staatlich vorgegebene politische, gesellschaftliche und soziale Richtung festgestellt werden, die junge Menschen einschlagen sollen. Welche edukativen Ziele der politischen Bildung werden verfolgt? Was sollen Sch{\"u}ler lernen, um mit diesen Kompetenzen die Zukunft ihres Kollektivs zu gestalten? Wo liegen die Gemeinsamkeiten und Unterschiede zweier Staaten, in unserem Fall Deutschlands und Polens, im Hinblick auf die schulische politische Bildung? Beantwortet werden diese Fragestellungen durch das Anwenden zweier Methoden der qualitativen Sozialforschung, der komparativen Inhaltsanalyse, zum einen der strukturierenden zum anderen der induktiven. Davor erfolgt eine komparativ quantitative Untersuchung, die den Umfang der Unterrichtszeit in den Leitf{\"a}chern f{\"u}r politische Bildung in allen Bundesl{\"a}ndern und in Polen vergleicht, was einer empirischen Totalerhebung der komplex umfangreichen Daten entspricht. Die quantitativen Forschungsergebnisse zeigen deutliche Differenzen zwischen Deutschland und Polen, in einem der beiden Staaten wird signifikant mehr Zeit f{\"u}r politische Bildung im Leitfach dieser Disziplin investiert als im anderen. Anhand der qualitativen Daten ist zu erkennen, dass einerseits eine gemeinsame Grundbasis von Kompetenzen der politischen Bildung zwischen Deutschland und Polen besteht. Anderseits stechen in beiden L{\"a}ndern eindeutige Unterschiede hervor, deren Ursprung zum einen historische Erfahrungen der Nationen und Staaten abbildet, zum anderen aktuell gegens{\"a}tzliche politische Interessen untermauert.},
  subject      = {Politische Bildung},
  language  = {de}
}
@phdthesis{Nolda2024,
  author    = {Nolda, Markus},
  title     = {Gender und Moraldidaxe : Zur Konstruktion von Geschlecht im ‚Welschen Gast' und den ‚Winsbeckischen Gedichten'},
  doi       = {10.25972/OPUS-35999},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359996},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Im Zentrum der Arbeit stehen als zwei Werke der hochmittelalterlichen Moraldidaxe: der ‚Welsche Gast' sowie die in zeitlicher N{\"a}he entstandenen ‚Winsbeckischen Gedichte'. Bei aller formalen Unterschiedlichkeit der Texte werden sie dadurch geeint, dass sie sowohl m{\"a}nnliches als auch weibliches Verhalten thematisieren, wobei der ‚Welsche Gast' in seiner Herren- und F{\"u}rstenlehre auch ein {\"a}lteres Publikum anspricht, w{\"a}hrend sich die Hofzucht des ‚Welschen Gasts' sowie ‚Winsbecke' und ‚Winsbeckin' auf heranwachsende Adlige beschr{\"a}nken. Ziel ist es, die Konstruktion von Geschlecht aufzudecken, wobei Analysemethoden der modernen sozialphilosophischen Forschung zum Einsatz kommen. Michel Foucault bietet mit seiner Diskursanalyse ein probates Mittel, gesellschaftliche Zust{\"a}nde und die Konstruktion von Identit{\"a}ten aufzudecken. Die amerikanische Philosophin Judith Butler greift bei ihren {\"U}berlegungen zur Konstruktion von Geschlecht unter anderem auf Foucault zur{\"u}ck und zeigt auf, welche Mechanismen bei der Gestaltung geschlechtlicher Identit{\"a}ten wirksam werden. Die Verkn{\"u}pfung moderner Theorie mit mittelalterlicher Moraldidaxe erweist sich insofern als fruchtbar und sinnvoll, als gerade mittelalterliche (und - diskursiv tradiert - auch {\"a}ltere) Vorstellungen von Geschlecht bzw. rollenad{\"a}quatem Verhalten ihren Niederschlag noch in moderner Ratgeberliteratur (z. B. M{\"a}dchenerziehungsschriften der 1950er Jahre) finden. So kann als Mittel der Analyse auf die von Judith Butler inspirierte Gendertheorie zur{\"u}ckgegriffen werden kann, ohne die Gegebenheiten der mittelalterlichen Literatur und die Restriktionen der Gattung zu vernachl{\"a}ssigen. Zu diesem Zweck werden in der Arbeit - anders als bislang {\"u}blich - die Gesamttexte (und nicht nur besonders auff{\"a}llige ‚Stellen' der Didaxen) hinsichtlich der in ihnen enthaltenen Bilder von Weiblichkeit bzw. M{\"a}nnlichkeit formal und inhaltlich untersucht. Beim ‚Welschen Gast werden zudem die zahlreichen Visualisierungen in die Einzelanalysen und bei den ‚Winsbeckischen Gedichten' nicht nur der an M{\"a}nner und der an Frauen gerichtete Teil, sondern auch die Parodie des Winsbecken miteinbezogen. Nach einer ausf{\"u}hrlichen Kl{\"a}rung der theoretischen und literaturwissenschaftlichen Voraussetzungen (Gender und Genderforschung, Performativit{\"a}t und Performanz, lehrhafte Dichtung im Mittelalter) wird das Korpus nach den Gesichtspunkten • Redeverhalten • K{\"o}rperverhalten • Emotionales Verhalten, Tugenden und Laster untersucht und die Ergebnisse in einem Schlußkapitel zusammengefasst. Die Studie kn{\"u}pft an das Interesse der feministischen Literaturwissenschaft an, ber{\"u}cksichtigt aber das geschlechter{\"u}bergreifende Genderkonzept und w{\"u}rdigt im Sinne eines close reading explizit den literarischen Charakter der Texte (strukturelle Performativit{\"a}t) sowie den symbolischen der Abbildungen. Im Ergebnis k{\"o}nnen Spielr{\"a}ume der grunds{\"a}tzlich an patriarchaler Hierarchie und st{\"a}ndischer Stabilit{\"a}t orientierten Gattung im Hinblick auf die Genderfrage ausgemacht werden, die Ausbr{\"u}che aus den vorgegebenen und damit intelligiblen Rahmungen erm{\"o}glichen (z.B. bei den verwendeten Metaphern), aber auch ‚R{\"u}ckschritte' demonstrierten (z.B. bei der in einzelnen Illustrationen erkennbaren, im begleitenden Text aber nicht nachweisbaren Misogynie). Dennoch wird ein m{\"a}nnlicher Blick auf eine Welt deutlich, in der die Frau meist als schm{\"u}ckendes Beiwerk fungiert, deren Handlungsmacht sich auf das ‚H{\"a}usliche' beschr{\"a}nkt. Raumanmaßung steht nur M{\"a}nnern offen, wobei der Radius der Handelnden von Alter und Stand beschr{\"a}nkt wird.},
  subject      = {Mittelhochdeutsch},
  language  = {de}
}
@phdthesis{Krause2024,
  author    = {Krause, Julian},
  title     = {Auswirkungen des Klimawandels auf charakteristische B{\"o}den in Unterfranken unter Ber{\"u}cksichtigung bodenhydrologischer Monitoringdaten (2018 bis 2022)},
  doi       = {10.25972/OPUS-36066},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360668},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die mit dem Klimawandel einhergehenden Umweltver{\"a}nderungen, wie steigende Temperaturen, Abnahme der Sommer- und Zunahme der Winterniederschl{\"a}ge, h{\"a}ufigere und l{\"a}ngere Trockenperioden, zunehmende Starkniederschl{\"a}ge, St{\"u}rme und Hitzewellen betreffen besonders den Bodenwasserhaushalt in seiner zentralen Regelungsfunktion f{\"u}r den Landschaftswasserhaushalt. Von der Wasserverf{\"u}gbarkeit im Boden h{\"a}ngen zu einem sehr hohen Grad auch die Ertr{\"a}ge der Land- und Forstwirtschaft ab. Eine besonders große Bedeutung kommt dabei der Wasserspeicherkapazit{\"a}t der B{\"o}den zu, da w{\"a}hrend einer Trockenphase die effektiven Niederschl{\"a}ge den Wasserbedarf der Pflanzen nicht decken k{\"o}nnen und das bereits gespeicherte Bodenwasser das {\"U}berleben der Pflanzen sicherstellen kann. F{\"u}r die land- und forstwirtschaftlichen Akteure sind in diesem Kontext quantitative und qualitative Aussagen zu den Auswirkungen des Klimawandels auf den Boden essenziell, um die notwendigen Anpassungsmaßnahmen f{\"u}r ihre Betriebe treffen zu k{\"o}nnen. Zielsetzungen der vorliegenden Arbeit bestehen darin, die Dynamik der Bodenfeuchte in unterfr{\"a}nkischen B{\"o}den besser zu verstehen, die Datenlage zum Verlauf der Bodenfeuchte zu verbessern und die Auswirkungen von prognostizierten klimatischen Parametern absch{\"a}tzen zu k{\"o}nnen. Hierzu wurden an sechs f{\"u}r ihre jeweiligen Naturr{\"a}ume und hinsichtlich ihrer anthropogenen Nutzung charakteristischen Standorten meteorologisch-bodenhydrologische Messstationen installiert. Die Messstationen befinden sich in einem Rigosol auf Buntsandstein in einem Weinberg bei B{\"u}rgstadt sowie auf einer Parabraunerde im L{\"o}ssgebiet bei Herchsheim unter Ackernutzung. Am {\"U}bergang von Muschelkalk in Keuper befinden sich die Stationen in Obbach, wo eine Braunerde unter Ackernutzung vorliegt und im Forst des Universit{\"a}tswalds Sailershausen werden die Untersuchungen in einer Braunerde-Terra fusca durchgef{\"u}hrt. Im Forst befinden sich auch die Stationen in Oberrimbach mit Braunerden aus Sandsteinkeuper und in Willmars mit Braunerden aus Buntsandstein. Der Beobachtungszeitraum dieser Arbeit reicht von Juli 2018 bis November 2022. In diesen Zeitraum fiel die dreij{\"a}hrige D{\"u}rre von 2018 bis 2020, das Jahr 2021 mit einem durchschnittlichen Witterungsverlauf und das D{\"u}rrejahr 2022. Das Langzeitmonitoring wurde von umfangreichen Gel{\"a}nde- und Laboranalysen der grundlegenden bodenkundlichen Parameter der Bodenprofile und der Standorte begleitet. Die bodengeographischen-geomorphologischen Standortanalysen bilden zusammen mit den qualitativen Auswertungen der Bodenfeuchtezeitreihen die Grundlage f{\"u}r Einsch{\"a}tzungen zu den Auswirkungen des Klimawandels auf den Bodenwasserhaushalt. Verl{\"a}ssliche Aussagen zum Bodenwasserhaushalt k{\"o}nnen nur auf Grundlage von zeitlich und r{\"a}umlich hoch aufgel{\"o}sten Daten getroffen werden. Bodenfeuchtezeitreihen zusammen mit den bodenphysikalischen Daten lagen in dieser Datenqualit{\"a}t f{\"u}r Unterfranken bisher nur sehr vereinzelt vor. Die vorliegenden Ergebnisse zeigen, dass die untersuchten B{\"o}den entsprechend den jeweiligen naturr{\"a}umlichen Gegebenheiten sehr unterschiedliche bodenhydrologische Eigenschaften aufweisen. W{\"a}hrend langer Trockenphasen k{\"o}nnen beispielsweise die Parabraunerden am Standort Herchsheim wegen ihrer h{\"o}heren Wasserspeicherkapazit{\"a}t die Pflanzen l{\"a}nger mit Wasser versorgen als die sandigen Braunerden am Standort Oberrimbach. Die Bodenfeuchteregime im Beobachtungszeitraum waren sehr stark vom Witterungsverlauf einzelner Jahre abh{\"a}ngig. Das Bodenfeuchteregime bei einem durchschnittlichen Witterungsverlauf wie in 2021 zeichnet sich durch eine langsame Abnahme der Bodenfeuchte ab Beginn der Vegetationsperiode im Fr{\"u}hjahr aus. Regelm{\"a}ßige Niederschl{\"a}ge im Fr{\"u}hjahr f{\"u}llen den oberfl{\"a}chennahen Bodenwasserspeicher immer wieder auf und sichern den Bodenwasservorrat in der Tiefe bis in den Hochsommer. Im Hochsommer k{\"o}nnen Pflanzen dann w{\"a}hrend der Trockenphasen ihren Wasserbedarf aus den tieferen Horizonten decken. Im Gegensatz dazu nimmt die Bodenfeuchte in D{\"u}rrejahren wie 2018 bis 2020 oder 2022 bereits im Fr{\"u}hjahr bis in die untersten Horizonte stark ab. Die nutzbare Feldkapazit{\"a}t ist zum Teil schon im Juni weitgehend ausgesch{\"o}pft, womit f{\"u}r sp{\"a}tere Trockenphasen kein Bodenwasser mehr zur Verf{\"u}gung steht. Die Herbst- und Winterniederschl{\"a}ge s{\"a}ttigen den Bodenwasservorrat wieder bis zur Feldkapazit{\"a}t auf. Bei tiefreichender Ersch{\"o}pfung des Bodenwassers wurde die Feldkapazit{\"a}t erst im Januar oder Februar erreicht. Im Zuge der land- und forstwirtschaftlichen Nutzung ist eine gute Datenlage zu den bodenkundlichen und stand{\"o}rtlichen Gegebenheiten f{\"u}r klimaadaptierte Anpassungsstrategien essentiell. Wichtige Zielsetzungen bestehen grunds{\"a}tzlich in der Erhaltung der Bodenfunktionen, in der Verbesserung der Infiltrationskapazit{\"a}t und Wasserspeicherkapazit{\"a}t. Hier kommt dem Boden als interaktive Austauschfl{\"a}che zwischen den Sph{\"a}ren und damit dem Bodenschutz eine zentrale Bedeutung zu. Die in Zukunft erwarteten klimatischen Bedingungen stellen an jeden Boden andere Herausforderungen, welchen mit stand{\"o}rtlich abgestimmten Bodenschutzmaßnahmen begegnet werden kann.},
  subject      = {Bodengeografie},
  language  = {de}
}