The potential for some microorganisms to survive in space is a compelling question of increasing relevance due to humanity's growing presence beyond Earth. Assessing microbial responses to the extreme stressors of space is relevant to the upper limits of life, planetary protection, and the biological sustainability of long-duration human spaceflight. The interdisciplinary research of this thesis, covers microbiology, biophysics and engineering validation, but is centred on the development of the new astrobiology exposure platform, ExocubeBio. This experiment will expose live microbial samples outside of the International Space Station, performing in-situ measurements of active cultures before preserving them for sample return.

The influence of the broad spectrum of solar radiation beyond Earth's atmosphere was a primary focus of this research, in which a diverse array of microbial taxa exhibited distinct resistances to simulated solar-ultraviolet radiation exposure. Methylobacterium radiotolerans, Halobacterium salinarum and Deinococcus radiodurans were each assessed as candidate species for inclusion onboard ExocubeBio. The results emphasised the influence of synergistic environmental stressors, raised questions regarding wavelength-specific radiation responses and the relative contributions of biological mechanisms and extracellular shielding. This also highlighted the necessity of sample preparation optimization. Additionally, Aspergillus calidoustus fungal conidia survived an array of environmental stressors associated with Mars, and is thus highlighted as a model species for planetary protection investigations. Each ExocubeBio subsystem was validated for experimental operation, including sample storage and exposure, rehydration and optical density measurement, compatibility with fluorescent organisms and fluorophores, and chemical fixation. Finally, singlecell infrared nanoscopy was established as a post-flight analytical technique, capable of simultaneously resolving morphological, biomolecular and metabolic heterogeneity information from individual fixed cells.

While each component of this research individually addresses an important topic in microbial astrobiology, together they describe the sequential development and define the operational parameters of this novel space biology experiment. As ExocubeBio transitions towards mission readiness, this thesis provides its scientific and technical foundation, and advances the capabilities of space biology instrumentation and our understanding of microbial life beyond Earth.

The present study comprises a literature review as well as experimental investigations into the kinematics of the accessory carpal bone and the evaluation of surgical treatment techniques for vertical fractures of this bone.

Computed tomography demonstrates that, the accessory carpal bone exhibits independent physiological motion during carpal flexion compared to the other carpal bones. In addition, the morphology of the bone is shown to be largely consistent in horses of comparable size, which may provide a basis for the development of standardized implant designs.

Dynamic analysis of vertical fractures of the accessory carpal bone reveals that carpal position has a significant influence on fragment behaviour. During flexion, widening of the fracture gap and proximal displacement of the palmar fragment are observed, whereas a neutral position and maximal extension result in approximation of the fragments. These findings are of clinical relevance and suggest that the carpus should be maintained in an extended position during surgical repair as well as during postoperative management.

Furthermore, the biomechanical stability of two osteosynthesis techniques is evaluated. Both methods prove to be feasible for repair of vertical fracture of the accessory carpal bone. However, neither results in a complete restoration of the native mechanical strength of the bone. Three clinical cases with a comparable fracture configurations were treated using similar techniques had a successful outcome; however, no reliable conclusions can be drawn from this.

In conclusion, the present study demonstrates that the accessory carpal bone is a dynamic structure with position-dependent fracture behaviour. The findings provide important insights for the optimization of surgical techniques and implant design. Further studies, particularly under in vivo conditions and including long-term comparisons between conservative and surgical treatment in larger cohorts, are required to further elucidate the pathogenesis of accessory carpal bone fractures in a vertical plane and to improve clinical outcomes.

AMR is increasingly recognised as a One Health problem that involves not only clinical settings but also environmental reservoirs. In broiler production, ESBL Escherichia (E.) coli can emerge and spread within flocks and subsequently enter the environment through land application of broiler litter. Once released into agricultural fields, bacteria may persist in soil, be mobilised by rainfall runoff, and reach surface waters used for crop irrigation and recreational activities. These pathways link farm emissions to human exposure through multiple intermediate processes-environmental survival, partitioning between soil particles and water, hydrological mobilisation, and in-stream fate (decay and dilution)-that are variable, uncertain, and strongly site-dependent. This cumulative thesis, therefore, aimed to connect broiler-origin ESBL E. coli emissions to human exposure via environmental pathways using a modular quantitative microbial risk assessment (QMRA) framework that combines evidence synthesis with mechanistic modelling.

The thesis consists of three studies. First, an exploratory review (Paper 1) synthesised evidence on manure-to-environment transmission routes and mitigation options, with the specific objective of informing pathway selection and parameterisation for modelling. Second, an end-to-end QMRA (Paper 2) linked within-flock dynamics and litter contamination to downstream environmental compartments (soil and river) and ultimately to exposure through fresh lettuce consumption, translating exposure to health outcomes expressed as disability-adjusted life years (DALYs). Third, the QMRA framework was extended (Paper 3) to recreational water, quantifying ingestion exposure for adults and children swimming downstream of a litter-amended field and DALYs. Across the three papers, the thesis addresses key knowledge gaps: (i) quantifying a farm-level source term (end-cycle litter concentration/load) suitable for environmental propagation, (ii) modelling soil-to-river connectivity via partitioning and wash-off, (iii) representing irrigation-mediated contamination of leafy greens and event-based recreational exposure, and (iv) identifying dominant Drivers of variability through global sensitivity analysis to guide data collection and risk management.

Methods: Paper 1 applied a targeted literature search and narrative synthesis approach, identifying 50 studies relevant to manure-derived E. coli transfer to soil, water, and crops and to mitigation options in agricultural settings. The review extracted quantitative information (e.g., persistence durations, concentration patterns, and transfer mechanisms) where possible and organised evidence by pathway (soil, crops, water) to highlight the most plausible routes for downstream modelling and intervention. A major purpose of the review within the thesis was to provide realistic parameter ranges and to identify where empirical evidence is scarce-particularly for resistant strains and water pathways-so that modelling assumptions and uncertainty ranges could be made explicit and defensible.

Papers 2 and 3 implemented a modular, stochastic QMRA. The upstream farm module simulated a 36-day broiler production cycle using a compartmental transmission structure and mass-balance shedding to generate an end-cycle litter concentration that acts as the source term for environmental modules. A soil module propagated litter-derived loads on fields using first-order die-off and introduced a partitioning concept to represent a “mobile fraction” available for mobilisation. Field-to-river transfer was represented via runoff-driven wash-off of the mobile fraction. River concentrations were then updated over time using a Mancini-type first-order in-stream decay formulation with modifiers for environmental conditions (temperature, light-related terms, depth, and salinity) and dilution in an effective mixed volume, producing time-varying concentrations in receiving waters. In Paper 2, river concentrations were linked to lettuce contamination via irrigation transfer, on-leaf adhesion, biphasic die-off, and washing scenarios to estimate a serving-level dose (CFU/100 g). In Paper 3, the river concentration time series was routed to a bathing reach and combined with age-specific ingestion distributions to estimate single-event doses for adults and children. Both QMRAs translated doses to health endpoints using a structured dose-to-outcome chain (gastrointestinal colonisation, urinary colonisation, urinary tract infection) and reported health burden as DALY per exposure event or serving. Across modules, uncertainty and variability were propagated via Monte Carlo simulation (1,000 iterations), and global sensitivity analyses (e.g., partial rank correlation coefficients) were used to rank key drivers of exposure variability.

Results: The literature review (Paper 1) showed that E. coli persistence in soil is highly variable and strongly dependent on manure type, treatment status, and environmental conditions, ranging from less than 30 days for composted manures to more than 200 days under cool, moist conditions. The review further indicated that contamination of surface waters is most consistently associated with rainfall-driven runoff, whereas groundwater contamination appears less frequent and more context-dependent. For crops, direct contamination from manure application can occur, but the review highlighted irrigation water as an often dominant and practically important pathway for leafy greens. Across studies, composting and other manure treatments, short-term storage, and adherence to pre-harvest intervals repeatedly emerged as effective mitigation options, while the review also identified a relative scarcity of quantitative data specific to resistant strains and to the water pathway-limitations that constrain validation and transferability of models and motivate conservative uncertainty ranges. In the integrated farm-to-lettuce QMRA (Paper 2), the farm module predicted rapid within-flock spread and produced a mean end-cycle litter concentration of approximately 1.6 x 10 to the power of 4 CFU/g. Soil surface loads declined from 3.2 x 10 to the power of 7 CFU/m² shortly after application to 8.6 x 10 to the power of 5 CFU/m² by day 100. Runoff and in-stream fate processes generated river concentrations on the order of 6.0 x 10 to the power of -2 CFU/mL after ten days in the modelled scenario. At the consumer endpoint, estimated exposure from lettuce consumption was ≈1.7 CFU per 100 g serving when lettuce was planted one day after spreading, decreasing to 7.6 x 10 to the power of -3 CFU/100 g at a 150-day interval; simple household washing reduced exposure by roughly 90%. When mapped through the dose-to-health framework, the predicted urinary tract infection (UTI) risk per serving ranged from 9.0 x 10 to the power of -9 to 4.6 x 10 to the power of -12, corresponding to DALY losses between 10 to the power of -8 and 10 to the power of -11 per serving depending on timing scenarios. Global sensitivity analysis indicated that soil-water partitioning and decay parameters were dominant drivers of exposure variability, consistent with the central role of mobilisation and persistence in controlling downstream concentrations and irrigation water quality.

In the farm-to-recreational water QMRA (Paper 3), predicted swimmer exposures were strongly time-dependent and concentrated shortly after litter application. Under a conservative/worst-case scenario, mean single-event doses on day 1 were 2.95 CFU for adults (95% uncertainty interval [UI] 0.14-6.11) and 8.78 CFU for children (UI 0.56-17.20). These doses translated into low probabilities of downstream health endpoints, with DALY losses per swim event on the order of 10 to the power of -7 to 10 to the power of -10, and concentrations and doses declining markedly over time. Uncertainty was dominated by fate-and-transport parameters rather than by behavioural parameters alone. In particular, stronger particle binding (higher sorption/partitioning), faster in-stream decay, and larger effective volumes reduced exposure, whereas higher wash-off fractions increased river concentrations and subsequent doses. The modelling results were consistent with the notion that recreational-water risks linked to agricultural applications may be short-lived and event-driven, supporting the relevance of targeted, time-sensitive monitoring or advisories (e.g., after litter application) rather than continuous high-intensity sampling.

Discussion and conclusions: Taken together, the three studies demonstrate a coherent pathway from broiler barns to human exposure through soil and surface waters, while also showing strong attenuation between source and receptor. Across both the lettuce and swimming pathways, reductions of several orders of magnitude occur through combinations of soil die-off, limited mobilisation (mobile fraction and wash-off), dilution, and in-stream decay. Nevertheless, the models indicate that short-lived peaks can occur after land application under the assumed daily export scheme and decline thereafter. Runoff-related peaks are plausible in reality but are not explicitly simulated at storm-event resolution. The integrated modelling also supports the central conclusion that environmental fate and transport dominate exposure variability: parameters controlling partitioning between sorbed and mobile phases, wash-off during runoff, and in-stream decay and effective volume consistently rank among the most influential drivers, while farm-scale source parameters often play a secondary role once downstream attenuation and dilution are accounted for. Nevertheless, farm parameters are still critical for risk management.

From a risk-management perspective, the thesis highlights several practical leverage points. First, upstream controls that reduce viable loads at the point of field application, particularly composting, appropriate storage, and adherence to pre-harvest intervals-are supported by both the evidence synthesis and the modelling framework as effective strategies to reduce subsequent environmental loading. Second, “field-edge” and hydrology-linked controls that reduce mobilisation (e.g., application timing relative to forecast rainfall, incorporation where appropriate, and runoff mitigation measures) are expected to reduce short-lived concentration peaks that drive exposure opportunities. Third, downstream measures remain important for exposure reduction: in the lettuce pathway, consumer-level washing reduces dose substantially even though it cannot fully compensate for poor irrigation water quality, and in the recreational pathway, advisories or monitoring triggered by high-risk windows (post spreading and post runoff) may be a rational approach given the transient nature of predicted exposures.

Finally, the thesis underscores the value of a modular QMRA for environmental AMR: it enables consistent propagation of uncertainty from farm to human endpoints, supports crosspathway comparisons through harmonised health metrics (DALYs), and provides a structured way to prioritise data collection by identifying which parameters most strongly control exposure outcomes. At the same time, results should be interpreted in light of limitations highlighted by the review: quantitative evidence for resistant strains and water pathways remains relatively sparse, and several parameters (e.g., partitioning and decay modifiers) are context-dependent and would benefit from local measurement for site-specific risk assessments. Overall, this thesis provides an integrated, uncertainty-aware framework linking broiler-origin ESBL E. coli emissions to human exposure through environmental pathways, demonstrating generally low predicted health burdens under modelled scenarios but emphasising the importance of eventdriven peaks associated with land-application events (captured at daily resolution in the model), and, based on monitoring evidence, the potential for rainfall-driven peaks in real catchments.

Introduction: Crimean-Congo hemorrhagic fever (CCHF) poses significant public health and economic threats, particularly in Sub-Saharan Africa (SSA), where mixed croplivestock farming practices and close human-animal interactions facilitate zoonotic transmission. This study aimed to investigate the seroprevalence of CCHF virus (CCHFV) in humans and livestock, characterise risk factors for exposure, and assess knowledge, attitudes, and practices (KAP) related to CCHF and other zoonotic diseases in rural mixed farming communities of Burkina Faso. Additionally, spatial risk mapping of CCHF outbreaks across Sub-Saharan Africa was performed to delineate high-risk areas and identify the underlying ecological factors associated with the outbreaks.

Methods: A cross-sectional linked human-animal study was conducted involving 149 rural households and 717 farmers from sixteen randomly selected villages in two Burkina Faso administrative regions. Human socio-demographic data and serum samples alongside livestock biodata and sera (from 666 cattle, 659 sheep, and 970 goats) were collected. Serological testing utilised multi-species ELISA assays to detect CCHFV antibodies. Additionally, climatic and ecological spatial datasets, including bioclimatic variables, digital elevation, land cover, and population density layers, were integrated with outbreak data spanning 1981 to 2022 from multiple SSA countries to model CCHF risk. Statistical analyses comprised descriptive statistics, multilevel logistic regression for seroprevalence risk factors, Fisher's exact tests for human exposure assessment, and a seemingly unrelated regression (SUR) model for KAP determinants. A Bayesian hierarchical spatial modelling framework accounting for spatial autocorrelation was employed for risk mapping.

Results: The overall CCHFV seroprevalence was 3.1% in humans, 54% in cattle, and 5.2% in small ruminants, with sheep showing higher seropositivity than goats. Exposure clustered significantly at the household level for both cattle and small ruminants. Key individual and household risk factors for seropositivity included older age, female sex (in cattle), longer grazing distances, and tick infestation. Ecological factors such as high aridity index and steeper slopes were significantly associated with CCHFV exposure. Among farmers, risky attitudes and practices related to livestock management increased infection risk, with male gender and distance from grazing areas significantly influencing KAP scores. Spatial risk mapping across the SSA identified elevated CCHF risk primarily in the arid and semi-arid zones of West Africa (Sahelian region), Central Africa, and Eastern and Southern Africa, with ecological factors such as grassland, bare soil, and shrub cover serving as positive predictors. Conversely, higher precipitation, mean temperature, and slope negatively correlated with outbreak risk.

Conclusion: This comprehensive investigation establishes that CCHFV is actively circulating among humans and livestock in rural Burkina Faso, with significant sociodemographic, ecological, and livestock management factors modulating exposure risk. The identification of spatially explicit risk areas across Sub-Saharan Africa provides actionable insights for targeted surveillance and control efforts under the One Health framework. Enhancing awareness and promoting biosecurity measures in farming communities is imperative to mitigate CCHF transmission. These findings offer a foundational evidence base supporting publicly tailored interventions and highlight directions for future research, including refinement of risk maps, socio-anthropological studies, and molecular investigations of viral ecology to improve disease prevention and preparedness in endemic regions.

Keywords: Crimean-Congo hemorrhagic fever, seroprevalence, mixed crop-livestock farming, risk factors, Burkina Faso, spatial risk mapping, One Health, knowledge-attitudespractices, multilevel logistic regression, Bayesian hierarchical model.

Die Vielseitigkeit stellt hohe physische und psychische Anforderungen an Pferd und Reiter, insbesondere während der Geländeprüfung, die durch submaximale bis hochintensive Belastungen gekennzeichnet ist. Ziel dieser Dissertation war es, Ermüdung und Erholung bei Vielseitigkeitspferden ganzheitlich zu erfassen und die Eignung subjektiver Selbstauskünfte sowie objektiver leistungsdiagnostischer Parameter für ein praxisnahes Monitoring zu bewerten.

Hierzu wurden zwei komplementäre Studien durchgeführt. In der ersten Studie wurde ein aus dem humanen Hochleistungssport adaptierter Kurzfragebogen auf Basis der Short Recovery and Stress Scale (SRSS) eingesetzt, mit dem Elite-Vielseitigkeitsreiter während einer Wettkampfsaison regelmäßig das eigene Wohlbefinden sowie das ihrer Pferde bewerteten. Die Ergebnisse zeigten eine signifikante positive Korrelation zwischen Reiter- und Pferdebewertungen sowie Zusammenhänge mit Trainingsform, Weidezugang und Wettkampferfolg. Gleichzeitig wurde deutlich, dass subjektive Einschätzungen stark von der individuellen Wahrnehmung der Reiter beeinflusst sind und insbesondere bei niedrigen Bewertungswerten an Aussagekraft verlieren.

Die zweite Studie untersuchte objektive Marker der Muskel- und Herzbelastung. Hierzu wurden bei denselben Pferden vor, 30 Minuten nach und 24 Stunden nach Geländeritten die Muskelenzyme Kreatinkinase (CK) und Aspartat-Aminotransferase (AST) sowie kardiales Troponin I (cTnI) bestimmt und mit echokardiographischen Gewebedopplerparametern der Myokardfunktion kombiniert. CK und AST zeigten erwartungsgemäße, belastungsabhängige Anstiege mit rascher Erholung, während cTnI nur geringfügig anstieg, jedoch in signifikanter Beziehung zur frühen diastolischen Myokardgeschwindigkeit (Em) stand. Diese Befunde deuten auf eine subklinische, reversible kardiale Ermüdung hin, die nur durch die Kombination funktioneller Bildgebung und hochsensitiver Biomarker erfassbar ist.

Insgesamt belegen die Ergebnisse, dass weder subjektive noch objektive Verfahren allein die Komplexität von Ermüdung und Erholung vollständig abbilden können. Ein multimodales Monitoringkonzept, das tägliche Selbstauskünfte mit wiederholten biometrischen und echokardiographischen Messungen kombiniert, ermöglicht jedoch eine frühzeitige Identifikation belastungsbedingter Anpassungen. Dies bietet ein wertvolles Instrument zur individualisierten Trainingssteuerung, zur Prävention von Überlastung und zur langfristigen Gesunderhaltung von Vielseitigkeitspferden.

The vascular endothelium maintains tissue homeostasis while retaining the capacity to become activated and undergo remodeling in response to physiological and pathological cues. Actin remodeling in endothelial cells (ECs) is widely recognized as a key regulator of barrier integrity and angiogenic sprouting through its coordination with adherens junction (AJ) dynamics. However, the contribution of branched actin networks to the integration of cell-cell and cell-matrix adhesion during these processes remains less well understood. NCK-associated protein 1 (NCKAP1) is a core component of the WAVE regulatory complex (WRC), which promotes Arp2/3-dependent branched actin polymerization and lamellipodia formation. Therefore, this study investigated how NCKAP1-dependent branched actin remodeling coordinates AJ and focal adhesion (FA) dynamics during endothelial barrier formation and angiogenic sprouting. Using siRNA-mediated knockdown, we found that NCKAP1 depletion disrupted lamellipodia formation, delayed endothelial barrier establishment, and impaired angiogenic sprouting, whereas mature barrier integrity remained largely preserved. Under basal conditions, NCKAP1-deficient ECs exhibited elongated FAs and a reduced ratio of phosphorylated to total paxillin, consistent with impaired FA turnover. NCKAP1 depletion further attenuated FAK and paxillin phosphorylation in response to vascular endothelial growth factor (VEGF), suggesting that impaired VEGF-induced FA signaling may contribute to the defective angiogenic response of NCKAP1-deficient ECs. Further exploratory analyses revealed alterations in YAP/TAZ signaling and attenuated SMAD1-TAZ association following NCKAP1 depletion, suggesting a potential link between NCKAP1-dependent actin cytoskeletal remodeling, mechanotransduction, and growth factor-induced transcriptional responses. Collectively, these findings extend the established role of WRC-Arp2/3-dependent branched actin networks in endothelial biology by revealing their involvement in coordinating both AJ and FA dynamics. This coordination appears particularly important during junction formation and angiogenic sprouting and may also contribute to growth factor responses, while the integrity of the established endothelial barrier can remain largely preserved despite impaired adhesion dynamics.

Bone formation during embryonic development requires the rapid and sustained transport of large amounts of calcium through the circulation to sites of mineral deposition. In avian embryos, this process coincides with a physiological transition in calcium supply, shifting from limited yolk reserves to large-scale mobilization from the eggshell. This transition is facilitated by the chorioallantoic membrane (CAM), which mediates eggshell demineralization and calcium release into the bloodstream. While vesicle-associated mineral transport has been increasingly recognized at the cellular level, it remains unclear how calcium delivery through the vasculature is organized and how transport is regulated and scaled during rapid skeletal growth. To address these questions, a cryogenic correlative light and electron microscopy (cryo-CLEM) workflow was developed to enable targeted imaging of vascular regions in the embryonic quail femur by correlating fluorescent endothelial labelling with 3D cryo-Focused Ion Beam-Scanning Electron Microscopy (cryo-FIB-SEM) ultrastructural imaging. In addition, multiscale imaging was performed by integrating micro-Computed Tomography (µCT) with cryo-FIB-SEM imaging and quantitative analysis across several developmental stages. The cryogenic conditions were essential to preserve cellular and extracellular structures in a close-to-native hydrated state, maintaining ultrastructural integrity of mineral precursors as well as cellular and extracellular matrices. The results revealed mineral-containing vesicles within the vascular lumen, endothelial cells, and bone-forming cells, indicating a direct link between blood vessels and sites of mineral deposition. Across development, mineralized bone volume increased in an accelerated, nonlinear manner, reflecting the geometric expansion and thickening of the embryonic bone. This acceleration in mineralization activity appears to result primarily from an increased number of bone-forming cells, rather than a greater mineralization workload for individual cells. These findings support a hierarchical organization of mineral transport, in which vesicle-mediated pathways, in addition to ion-based mechanisms, contribute to mineral delivery through the vasculature. Vascular delivery, intracellular processing, and tissue growth appear to be tightly coordinated. Within cells, vesicles are actively transported at relatively constant rates despite substantial skeletal growth, with the increase in mineralized volume being associated with the expansion of mineralizing surfaces and increased bone-forming cell numbers. This work highlights the relevance of avian models for understanding basic principles of skeletal development and provides a methodological and conceptual framework for studying mineral transport in complex tissues, with potential implications for pathological mineralization and bone-related diseases.

Breast cancer is by far the most common cancer among women. Abnormal glycan antigens expressed in anomalous patterns on cancers, called tumor associated carbohydrate antigens (TACAs), represent important cancer hallmarks. Globo-H and Gb5 are two TACAs of the globo-series glycosphingolipids (GSLs). They are found on various epithelial types of cancer e.g., breast cancer, and are involved in tumor progression and survival. Additionally, in healthy organisms Globo-H and Gb5, also known as stage specific antigens, are present on embryonic cells. However, they disappear in further development, and they reoccur on cancer cells due to the deranged glycan biosynthesis in carcinogenesis. Their high abundance on epithelial tumors and expression restricted to either embryonic or cancer cells make them highly specific targets for the development of cancer treatments and diagnostic tools.

The aim of this thesis was to expand the anti-glycan antibody (Ab) toolbox through the development of additional Ab fragments targeting Globo-H and Gb5 by means of a phage display method. It is a scientifically recognized technology with the ultimate honor of Nobel Prize awarded in 2018. This method involves bacteriophage displaying Ab fragments encoded in their genome in a form of the large-sized library. Phage display allows to identify the peptide ligand to a given target molecule, yet it is rarely applied for glycans. Since native glycans are inhomogeneous and difficult to obtain in sufficient amounts, synthetic, pure, and well-defined glycans were used to isolate potential Ab candidates from two phage display libraries: human naïve libraries HAL9/10 constructed by Prof. Dr. Michael Hust and colleagues from Technische Universität Braunschweig and an alpaca VHH Ab immune library constructed over the scope of this thesis.

The first project employed human naïve libraries HAL9/10 constructed from lymphocytes of 98 healthy donors. Panning was performed with the phage displaying single chain variable fragment (scFv) fusion proteins binding Globo-H/Gb5-BSA glycoconjugates immobilized to microtiter plates. Ten potential Ab binders were identified from libraries HAL9/10 and their format was changed for bivalency by fusing Fc domain of human immunoglobulin G1 (IgG1). Identified Ab candidates were further tested for binding with synthetic glycans on microarrays and by surface plasmon resonance (SPR), as well as with native glycans on cells via flow cytometry and confocal microscopy. Additionally, their protein stability was examined. Two Ab fusion proteins emerged as the most suitable candidates for further development: SH2186-E11 (5Y) and SH2187-2-F10 (9Y), both binding specifically to the globo-series GSLs. SH2187-2-F10 (9Y) is a promising scFv-hFc candidate binding to both synthetic and native glycans; however, SH2186-E11 (5Y) binds primarily to native glycans. Nevertheless, it exhibited extraordinary protein stability among the tested candidates. Moreover, sequencing revealed that SH2186-E11 (5Y) lacks the VL domain in the scFv format. Thus, only its VH domain was responsible for binding, which makes this binder smaller than e.g., SH2187-2-F10 (9Y).

The second project aimed at isolating camelid single domain Abs from the immune alpaca VHH library constructed over the scope of this thesis. A complete Ab development pipeline was established, starting with the alpaca immunization, through construction of DNA and phage display library, panning, and eventually, binding assays with the identified candidates. The panning was performed with synthetic Gb5 and Globo-H conjugated to magnetic beads. Eleven unique VHH and VH sequences were identified in the panning. VHH is an antigen binding domain of heavy chain-only Abs, while VH is its counterpart from conventional camelid IgG2 and 3. These sequences were subcloned into bacterial expression plasmids. Further, they were expressed in the cytoplasm of Escherichia coli (E. coli) SHuffle T7 as VHH/VH monomers and in the periplasm of E. coli XL-1 Blue MRF’ as fusion proteins with pIII minor coat phage protein or as monomers. The subsequent binding assays did not show the binding to the Globo-H/Gb5-BSA glycoconjugates.

In conclusion, the goal of the thesis was reached—the anti-glycan Ab toolbox was expanded with new promising Ab candidates. The identified candidates bound specifically to the globo-series GSLs and based on the further binding assays they may be employed with both synthetic and native glycans. With further steps such as synthetic affinity maturation and thermal stability improvements, SH2186-E11 (5Y) and SH2187-2-F10 (9Y) scFv-hFc fusion proteins could be employed as research, diagnostic and therapeutic tools. Additionally, SH2186-E11 (5Y) is a single domain Ab, despite being of human origin. To sum up, this work has proven that phage display may be adapted for the identification of Abs to glycans, which may be transferred into diagnostic and/or clinical settings.

DNA methylation is a fundamental epigenetic modification that plays a crucial role in regulating gene expression and cell differentiation. Multiple profiling technologies have been developed to generate DNA methylation maps with varying resolutions and genome coverage. In recent years, DNA methylation-based classification of tumors has emerged as a powerful and indispensable diagnostic technique. Traditional implementations relied on methylation microarrays to establish reference datasets, and most current classifiers remain constrained to a fixed set of methylation features from specific platforms. This limitation hampers their compatibility with other platforms, particularly emerging sequencing technologies. Among these, low-coverage nanopore sequencing stands out as one of the fastest and most cost-effective options. This thesis first introduces an ad-hoc Random Forest–based approach that enables robust tumor classification using sparse methylomes obtained from low-coverage nanopore data. Building upon this, a neural network–based machine learning framework named crossNN, is presented. crossNN enables accurate tumor classification from sparse methylomes generated across different platforms, regardless of variations in epigenomic coverage or sequencing depth. It surpasses both deep learning and conventional machine learning models in accuracy and computational efficiency while maintaining interpretability. With crossNN, a pan-cancer classifier was trained and validated to distinguish more than 170 tumor entities spanning all organ systems. Overall, this work demonstrates two sequential advances in DNA methylation-based tumor classification. First low-coverage nanopore sequencing is a viable and cost-effective route for methylation-based brain tumor classification via ad-hoc Random Forest algorithm. Second, the crossNN framework extends this concept by overcoming platform-specific feature constraints and enabling cross-platform, interpretable tumor classification. These developments pave the way for scalable, explainable, and clinically applicable DNA methylation-based diagnostics.  

Neuronal function depends on the maintenance of stable activity despite environmental perturbations. Neurons engage homeostatic plasticity mechanisms to maintain their activity within a functional range while preserving information acquired through experience-dependent changes. Several diseases par- ticularly prominent in humans have been associated with homeostatic modulation of synaptic efficacy and/or membrane excitability. Such changes may contribute to disease-related dysfunction, but may also arise as a consequence of pathology. At the same time, increasing evidence suggests that homeostatic plasticity responses are highly context dependent, making it essential to understand the intricacies of these processes in human neurons. Here, using patch-clamp electrophysiology, properties of human cortical pyramidal neurons were compared before and after more than 16 h of incubation in either control artificial cerebrospinal fluid (aCSF) or a moderately depolarising aCSF, supplemented with an additional 8 mM KCl. The high-potassium treatment consistently resulted in homeostatic downregulation of intrinsic excitability, as reflected by a reduction in firing frequency across three complementary experimental paradigms. In contrast, the length of the axon initial seg- ment showed only time-dependent shortening, rather than potassium-specific structural remodelling, under the same conditions. The perturbation appeared to preserve synaptic connectivity over the in- cubation period, whereas connectivity was reduced from 12% to 6% under control conditions. There was no evidence for homeostatic synaptic scaling. Together, these findings indicate that prolonged moderate depolarisation in human cortical neurons preferentially engages intrinsic, rather than synap- tic, homeostatic mechanisms, and highlights the importance of defining the conditions under which homeostatic plasticity operates in human cortical circuits.

This thesis addresses the human metabolism of beta-receptor-active ethanolamines and the quantitative analysis of the parent drugs and their phase I and phase II metabolites in human specimens. The investigations' three key aspects are 1) the biosynthesis of reference material, 2) the development of highly sensitive bioanalytical quantitation methods using chiral and achiral chromatography coupled to tandem mass spectrometry, and 3) the final quantitation of human urine and serum samples from administration studies. The achieved milestones were: First, a biosynthesis protocol for sulfonated phase II metabolites, including salbutamol-4’-O-sulfate and propranolol sulfate, was successfully developed using genetically modified S. pombe. The protocol rendered the external addition of the expensive cofactor PAPS superfluous (Manuscript III). Subsequent upscaling of salbutamol-4’-O-sulfate biosynthesis by human SULT1A3 in S. pombe enabled production of sulfoconjugated metabolites as a reference in bioanalytical quantitation (Manuscript IV). Notably, this biosynthesis is highly enantioselective for (R)-salbutamol. Second, the successful quantitation of salbutamol-4’-O-sulfate, alongside salbutamol and formoterol, was achieved by highly sensitive HPLC-MS/MS methods for urine and serum samples in a phase I clinical trial. The study results indicate that salbutamol and formoterol tend to reach higher concentrations in the urine and serum of females (Manuscript VI). Additionally, the development of further chiral and achiral HPLC-MS/MS methods enabled research on sulfonation rates of salbutamol. In a proof-of-concept study, it was demonstrated that oral administration and administration of enantiopure levosalbutamol can be indicated by the ratio of sulfonated to parent salbutamol in urine (Manuscripts IV & V). Third, the simultaneous chiral separation of propranolol and its ring-hydroxylated phase I metabolites (4’-, 5’-, and 7’-hydroxypropranolol) was successfully achieved by SFC-MS/MS as well as by two-dimensional HPLC-MS/MS (Manuscripts I & II). Quantitative bioanalysis by chiral SFC-MS/MS faced more obstacles than quantitative bioanalysis by chiral heart-cutting 2D-HPLC-MS/MS. Attempting quantitation of all ring-hydroxylated metabolites in bioanalytical SFC-MS/MS required the examination of several sample preparation methods, including dilute-and-inject, solid-phase extraction, and liquid-liquid extraction. The challenges of fast chiral bioanalytical SFC-MS/MS quantitation are discussed, focusing on recovery, quantitative and qualitative matrix effects, and the presence of phase II metabolites. The results were obtained by employing in vitro and in vivo metabolism models. The former includes isolated recombinant human enzymes and human enzymes expressed in genetically modified fission yeasts (S. pombe). Metabolism models in S. pombe were employed as whole-cell experiments for the production of reference substance and as permeabilized yeast-cell experiments (enzyme bags) for overview incubations. In vivo experiments were conducted in human volunteers in accordance with ethical standards. The investigations required the use of HPLC coupled to a diode array detector, unit mass spectrometry, tandem mass spectrometry, and high resolution mass spectrometry. SFC was hyphenated to tandem mass spectrometry. NMR analysis was needed for the quantitation and final structure elucidation of biosynthesized salbutamol-4’-O-sulfate and was performed in cooperation with the Institute of Pharmacy in Kiel. This work demonstrates the significance of the enantioselective acquisition and quantitation of beta-receptor-active ethanolamines in human specimens and highlights the potential of targeting their metabolites, particularly sulfonated phase II metabolites. The results enhance understanding of methodological developments in therapeutic drug monitoring, forensic analysis, and anti-doping control.

Mit dieser Studie wird ein übergeordnetes Ziel verfolgt: die theoretische und empirische Klärung der Rolle der Medien bei der Entstehung einer möglichen kollektiven nationalen und/oder regionalen Identität in Deutschland. Hintergrund der Fragestellung ist die auch 35 Jahre nach der Wiedervereinigung aktuelle Ost-West-Debatte. Ausgehend von der Annahme, dass die Bildung einer gemeinsamen kollektiven Identität in der Nachwendezeit nur unzureichend funktioniert hat, wird die besondere Rolle von Medien als Vermittlungsinstanz, vor allem der öffentlich-rechtliche Rundfunk mit seinem rechtlich-normativen Auftrag, betrachtet. Das Konzept der Medienkultur nach Hepp bildet das zentrale analytische Raster der theoretischen wie empirischen Aufbereitung der Konstruktion von kollektiver Identität in Deutschland. Vor dem Hintergrund zweier getrennter Medienkulturen in BRD und DDR bleibt offen, ob die formale Einigung und die damit einhergehende Schaffung eines gemeinsamen Kommunikationsraums auch tatsächlich zu einer neuen gemeinsamen Medienkultur geführt hat. Zur Klärung dieser Frage wird der Kreislauf der Medienkultur in ein überarbeitetes Encoding/Decoding-Modell nach Hall integriert und empirisch in ein modulares Mehrmethodendesign übersetzt. Mit drei Teilstudien wird je ein Faktor der Medienkultur empirisch untersucht: Produktion, Repräsentation und Aneignung. Auf Ebene der Produktion wird anhand von Desk Research eine strukturelle Unterrepräsentanz ostdeutscher Personen nachgewiesen. Mittels leitfadengestützten Expert:inneninterviews werden Rückschlüsse auf die Perspektiven von Akteuren aus dem Journalismus und der Journalismusausbildung zur Rolle von Medien bei der Konstruktion kollektiver Identität gezogen. Es kann gezeigt werden, dass die ungleiche Verteilung von Ressourcen und Entscheidungspositionen die Wahrscheinlichkeit erhöht, dass bestimmte Stimmen Eingang in den medialen Diskurs finden. Auf Ebene der Repräsentation wird die Konstruktion deutscher Identität im (über-)regionalen linearen öffentlich-rechtlichen Fernsehen mittels einer quantitativen Inhaltsanalyse von ARD/Das Erste, MDR und SWR untersucht. Neben einer hohen Sichtbarkeit von Deutschlandbezügen zeigen sich auch hier Asymmetrien. Ostdeutsche Bezüge sind im überregionalen Programm sowie im SWR unterrepräsentiert. Als relevant für Deutschland werden im überregionalen Programm überwiegend kontroverse Themen, im regionalen Programm vielmehr Kultur und alltägliche Lebensweltbezüge präsentiert. Identitätsanker werden regelmäßig gesetzt, vor allem durch Symbole sowie wirtschaftliche und sportliche Leistungen, während geteilte Werte und Normen oder gemeinsame Erinnerungen weniger relevant sind. Auf Ebene der Aneignung wurden Fokusgruppengespräche mit Ost- und Westdeutschen durchgeführt, um mehr über die Nutzung und Integration medialer Identitätsangebote in den jeweiligen Alltag zu erfahren. Die Befragten positionieren sich zurückhaltend, was den Einfluss der öffentlich-rechtlichen Angebote auf ihre Identitätskonstruktion angeht, implizit konnten jedoch Prägungen herausgearbeitet werden. Hinsichtlich der wahrgenommenen Repräsentation divergieren die Einschätzungen, sodass sich hier kein klares Bild zeichnen lässt. Es gibt Hinweise darauf, dass ostdeutsche Befragte eher eine Marginalisierung ihrer Perspektiven wahrnehmen. Die drei Teilstudien zusammengenommen erlauben eine Antwort auf die übergeordneten Forschungsfragen: Angebote zur Konstruktion von kollektiver Identität in Ost- und West-deutschland sind im Kreislauf der Medienkultur strukturell relevant, jedoch ungleich verteilt.

This dissertation examines the contested epistemological boundaries between science, culture and concepts of enchantment through a detailed analysis of J. B. Rhine’s parapsychological laboratory at Duke University and Wilhelm Reich’s experimental practices in mid-20th-century America. Rhine, transitioning from botany to psychical research, established laboratory-based studies of extrasensory perception (ESP), while Reich moved from psychoanalysis to developing his controversial theory of orgone, a purported universal life energy. Drawing on constructivist theories of science, boundary-work concepts, and theories of enchantment informed by Max Weber’s famous notion of the disenchantment of the world, I provide an in-depth analysis of their experimental methodologies, institutional contexts, and reception within scientific communities. The research demonstrates how these figures attempted to integrate enchanted elements into scientific discourse while challenging mechanistic paradigms. Through examination of archival materials, scientific publications, and media representations, I trace Rhine’s ESP experiments and Reich’s orgone research, revealing how they incorporated vitalist, Lamarckian, and spiritualist discourses into their experimental practices, creating flexible epistemological frameworks that accommodated uncertainty and enchantment. Despite their innovative approaches, both ultimately failed to establish new scientific paradigms due to methodological flaws, lack of expansive scientific networks, increasingly obsolete epistemological underpinnings, and the rigorous boundary-work of scientific thought collectives. Their enchanted practices epitomize the endpoint of enchanted sciences in America, illustrating how the epistemic borders of science became impermeable during the postwar years. The dissertation argues that while Rhine’s parapsychological research and Reich’s theories were marginalized by scientific communities, they significantly influenced popular culture and esotericism in the second half of the 20th century. By extending the historiographic focus on enchanted sciences beyond early 20th-century Europe, this project contributes to our understanding of how scientific knowledge is produced and how epistemic boundaries are negotiated and enforced.

Under the influence of neo-imperialism, Iran experienced a new form of colonial influence after World War II in the form of economic dependence, which also heralded profound cultural and political changes. In this context, Iranian intellectuals began to increasingly address questions of identity and modernity, seeking a middle ground between Western influence and Iranian traditions. This Third Space of hybrid cultural contacts and the accompanying discourses was characterised not least by complex interactions or even discursive contradictions, along whose lines of conflict identity was re-discussed. Not least, the social discourse took place in the literature of Iranian writers such as Sadeq Hedayat and Jamal Al-e Ahmad, whose works provide important insights into Iran's socio-political developments in the twentieth century. Hedayat's literature deals in particular with themes such as alienation and existential uncertainty, reflecting the cultural uprooting of broad sections of society between the pressure of modern Westernisation by the Pahlavi regime, traditional values, and the diversified discourse of intellectuals. His works illustrate the psychological and social fragmentation characteristic of the hybrid space. In a completely different way, Al-e Ahmad denounces the uncritical adoption of Western norms in his critique of “Westoxication” and calls for a revival of indigenous culture, not least from the perspective of Islam as a source of identity. In his writings, he formulates a vision of cultural hybridity that rejects both complete assimilation to the West and reactionary traditionalism. Instead, Al-e Ahmad advocated a decolonised modernity rooted in Iran's own ethical and cultural framework. Together, their works embody the debate on cultural identity within the Third Space and illustrate how Iranian intellectuals used hybrid discourses to resist neo-imperial rule and authoritarianism. Their approach challenged fixed or essentialist identities and opened up a fluid understanding of postcolonial Iranian identity.

Hydrogen produced by electrochemical water splitting is considered a promising energy carrier for future sustainable energy systems. However, the oxygen evolution reaction (OER) at the anode is the major kinetic bottleneck due to its complex multi-electron transfer mechanism. Among the various catalyst materials investigated for OER, transition-metal oxyhydroxides with bulk-phase catalytic activity have attracted considerable attention. Nevertheless, many aspects of their underlying electrochemical behavior and catalytic mechanism are still not fully clarified. In this study, cobalt-based oxyhydroxide electrocatalyst (CoCat) is employed as a model system for bulk-active catalysts for investigation of reaction kinetics. Electrochemical measurements are combined with operando spectroscopic techniques, including time-resolved X-ray absorption spectroscopy (XAS) and UV–Vis spectroscopy, in order to investigate the temporal evolution of oxidation-state changes and catalytic processes over a broad range of catalyst thicknesses and operating conditions. Additionally, electrochemical impedance spectroscopy (EIS) is employed to distinguish the characteristic timescales of double-layer charging, bulk redox transitions, and catalytic OER processes. Electric double-layer charging occurs on the microsecond timescale, followed by bulk cobalt oxidation-state transitions in the millisecond regime, whereas the catalytic OER process proceeds substantially more slowly. Correlation of time-domain measurements with impedance analysis enables assignment of equivalent circuit elements to physically meaningful electrochemical processes and provides a mechanistic interpretation of EIS parameters in terms of redox equilibration and catalytic turnover kinetics. Furthermore, temperature-dependent electrochemical measurements combined with operando XAS were performed to evaluate the activation energy parameters of the OER process and to investigate how the chemical state of the catalyst influences its catalytic activity. The analysis indicates that the Gibbs free energy of activation is determined predominantly by entropic contributions rather than solely by changes in the enthalpic energy barrier. Moreover, the results suggest that the applied potential does not directly lower the intrinsic activation barrier of the OER process, but instead controls the catalytic rate indirectly through changes in the oxidation state and population of reactive sites within the catalyst. The observed relationship between catalyst oxidation state, electrode potential, and catalytic current is described within an interaction-based framework, in which repulsive interactions between oxidized sites affect the thermodynamics of oxidation, while cooperative interactions enhance the reaction kinetics by reducing the activation energy. The temperature dependence of these interaction energies suggests a primarily entropic origin and highlights the balance between oxidation constraints and catalytic enhancement. Overall, this work establishes a comprehensive mechanistic picture, linking redox charge accumulation to changes in the chemical state of the catalyst, and ultimately to its catalytic activity, thereby providing new insight into the fundamental origin of potential- and temperature-dependent OER activity in bulk-active transition-metal oxyhydroxides.

High dietary salt intake is a major risk factor for non-communicable diseases such as hypertension and associated end-organ damage. Beyond elevating blood pressure, a high salt diet (HSD) alters the gut microbiome, modulates immune responses, and contributes to tissue injury. Immune cells, particularly their modulation by microbial signals, have emerged as key players in salt-related pathologies. Although intestinal immune cells are exposed to dietary salt shortly after ingestion and are capable of migrating to peripheral organs, their role in HSD-induced organ damage remains poorly understood. This thesis explores whether, and if so, how, high salt intake affects intestinal immune cell trafficking and activation, and whether these processes contribute to systemic inflammation and salt-induced tissue damage. To tag and trace intestinal immune cell migration in vivo, transgenic mice expressing the photoconvertible Kaede protein were used. Mice underwent two 3-week phases of high salt diet (HSD), separated by a 2-week normal salt diet (NSD) washout. NSD-fed mice served as controls, and animals were pretreated with L-NAME to sensitize the vasculature. Five days after photoconversion, immune cell trafficking and activation were analyzed using flow cytometry and bulk and single-cell RNA sequencing. In parallel, microbiome profiling was performed. In separate experiments within the same model, the impact of pharmacological interventions (FTY720, antibiotics) on immune trafficking was assessed. To investigate the functional relevance of B cells, a salt-sensitive mouse model with more severe organ damage (uninephrectomy and DOCA/HSD treatment) was used in combination with anti-CD20-mediated B cell depletion. Photoconversion-based tracing revealed widespread trafficking of intestinal immune cells to peripheral organs, including the spleen and kidney, with B cells emerging as the predominant migrating population. HSD induced substantial changes in intestinal gene expression and immune cell composition, and enhanced B cell migration to peripheral organs. FTY720 treatment confirmed S1P-dependent intestinal immune cell trafficking. HSD also altered homing and retention cues in both the intestine and kidney, and enhanced migratory programs in B cells. Changes in microbiome composition under HSD, along with the impact of antibiotic treatment on immune cell trafficking, highlight microbial signals as contributors to HSD-induced migration. B cell depletion exacerbated inflammation and kidney damage, indicating a protective role of B cells. HSD induced subset-specific B cell changes, particularly among gut-originating populations, characterized by enhanced IgA expression, elevated BCR signaling, activation, and cytokine production. Notably, IL-10 was upregulated alongside pro-inflammatory cytokines, suggesting a partial induction of a regulatory B cell phenotype under HSD. In summary, HSD shapes the phenotype and function of intestinal B cells and promotes their systemic migration, thereby modulating salt-induced immune responses and organ damage. This thesis identifies gut-originating B cells as key mediators linking mucosal and systemic immunity and uncovers immune migration pathways and regulatory mechanisms relevant to salt-sensitive disease. These findings enhance our understanding of salt-responsive immunity and may guide the development of novel therapeutic strategies targeting mucosal–systemic immune interactions to mitigate salt-associated health risks.

This cumulative dissertation examines the conditions under which data use beyond the original context of collection (data reuse) becomes transparent, accountable, and auditable in regulated environments. Despite expanding regulatory frameworks such as the GDPR and the EU AI Act and a growing repertoire of privacy-preserving data-sharing approaches, valuable data frequently remain underused because access, oversight, and justificatory conditions cannot be reliably organised across heterogeneous institutions and infrastructures. The dissertation therefore treats responsible data reuse as a socio-technical governance problem in which technical enablement, institutional constraints, and documentary evidence conditions must be aligned to make reuse trustworthy and reviewable in practice. Building on a systematic literature review that consolidates privacy-preserving and access-enabling approaches while highlighting unresolved governance and implementation tensions, the dissertation develops a cumulative argument in three steps: it first diagnoses why underuse persists even where data and technical solutions exist, emphasising intrinsic data frictions and missing intermediating structures that would institutionalise workable access pathways; it then benchmarks how open repository platforms govern compliance-relevant transparency by operationalising regulation-inspired expectations as machine-auditable documentation signals, with attention to downstream reuse contexts; and it finally derives an operationalisation perspective on auditable transparency at scale by specifying minimal evidence targets and platform-level mechanisms through which governance-relevant information can become inspectable and reviewable across heterogeneous settings.

Overall, the dissertation contributes an Information Systems perspective that links data reuse to platform governance and documentation-as-governance, clarifying what it takes to move from voluntary narrative disclosure toward auditable transparency as a practical condition of responsible reuse.

Benzimidazole (BZ) resistance in Haemonchus contortus, one of the most pathogenic blood-feeding gastrointestinal nematodes of small ruminants, represents a major challenge for sustainable parasite control. Benzimidazoles are proposed to bind to the isotype-1 β-tubulin subunit, inhibit microtubule polymerization, and disrupt essential cellular processes. Single nucleotide polymorphisms (F167Y, E198A, F200Y) in the isotype-1 β-tubulin gene are considered key markers of BZ resistance. To investigate the structural basis of BZ resistance, α/β-tubulin heterodimers from H. contortus (wild-type and BZ resistant variants) were modeled in silico and their interactions with albendazole (ABZ) were analyzed. Analyses revealed that ABZ weakens critical intradimeric contacts and prevents the transition from a curved to straight α/β-tubulin heterodimer conformation, whereas these interactions remain intact in resistant variants despite ABZ binding. To assess the functional effects of BZ binding, recombinant H. contortus isotype-1 α/β-tubulin heterodimers were expressed recombinantly in Leishmania tarentolae. Although the integration of the expression cassettes were confirmed, stable transgenic cell lines could not be established. The cells ceased proliferation, showed abnormal twitching, and expressed transcripts only transiently, indicating potential cytotoxic effects on the endogenous tubulin network. In parallel, deep-amplicon sequencing was used to quantify known and novel BZ-resistance associated polymorphisms in field samples from northeastern Germany. Alongside known polymorphisms, the novel E198G polymorphism in H. contortus and the F200Stop polymorphism in Trichostrongylus colubriformis were detected, both potentially associated with BZ resistance. Overall, these results integrate structural, functional, and genetic insights into BZ resistance in H. contortus and highlight the complexity of resistance development. The results underscore the importance of continuous monitoring, innovative control strategies, and polymorphism modeling. Together, these findings support the refinement of experimental models and contribute to improved strategies for the investigation and management of benzimidazole resistance in H. contortus.

The chlorine industry is currently characterized by linear material flows arising, among others, from difficulties in handling, storage, and transport of chlorine (Cl2) and hydrogen chloride (HCl). This limits the needed rethinking of processes towards a more sustainable approach focusing on circularity and resource efficiency. Herein, the potentials of bichlorides and polychlorides as alternative chemical platforms for HCl and Cl2 were investigated to valorize industrial side streams and support a more sustainable chlorine industry. Ammonium-based poly(hydrogen chloride) chlorates, so-called bichlorides, were introduced as stable, easy to handle HCl storage systems with significantly reduced vapor pressures. Among the investigated compounds, triethylmethylammonium bichloride ([NEt3Me][Cl(HCl)n]) was identified as promising candidate, reversibly binding up to n = 2.5 equivalents of HCl under ambient conditions. Beyond storage, the bichloride can be directly used as reagent, increasing process safety by shifting, e.g., the hydrochlorination of acetylene to vinyl chloride from the gas to the liquid phase. In combination with palladium(II)chloride, a highly active and stable catalytic system was obtained as viable alternative to currently used toxic and environmentally harmful mercury(II)chloride. Furthermore, technologies of Cl2 recovery have been investigated. The bichloride enables the efficient electrochemical regeneration of Cl2 from HCl in form of the corresponding polychloride. Using a simple undivided cell setup, no parasitic side reactions were observed overcoming difficulties associated with the electrolysis of neat HCl or hydrochloric acid. Complementarily, ion exchange resins providing ammonium chloride functions have been introduced as selective adsorber materials reversibly binding Cl2 under the formation of polymer-based polychlorides. Cl2 can be efficiently recovered from tail and waste gas streams by also enabling its upcycling to base chemicals like 1,2-dichloroethane or phosgene. In this way, the further use of otherwise downgraded Cl2 can be realized as an energy- and resource-efficient alternative to current performed neutralization processes. Overall, the presented concepts demonstrate how rethinking Cl2 chemistry through circular process design could enhance safety, resource efficiency, and sustainability in the chemical industry.

Die vorliegende Dissertation untersucht die Darstellung und Bewertung des Chinesischen im deutschsprachigen wissenschaftlichen Diskurs vom 17. bis zum 19. Jahrhundert und analysiert, in welchem Sinne die Sprache innerhalb der westlichen Grammatik- und Sprachtypologietradition als ein sprachwissenschaftlicher Sonderfall („schwarzes Schaf“) wahrgenommen wurde. Im Zentrum steht die Frage, wie die strukturellen Besonderheiten des Chinesischen – insbesondere sein isolierender Sprachbau – zur Anpassung und Erweiterung bestehender grammatischer und typologischer Konzepte beitrugen.

Die Analyse zeigt, dass die Wahrnehmung einer als paradox empfundenen Konstellation – einer vergleichsweise einfachen äußeren Sprachstruktur bei zugleich anerkannten kulturellen und geistigen Leistungen Chinas – maßgeblich die theoretischen Bemühungen beeinflusste, das Chinesische nicht als form- oder grammatiklos zu klassifizieren. Diese Spannung erforderte eine Neubewertung der Einordnung des Chinesischen innerhalb der etablierten Modelle der griechisch-lateinischen Grammatik und der vergleichenden Sprachwissenschaft und begünstigte die Entwicklung nicht-morphophonologischer, zunehmend verinnerlichter Erklärungsansätze.

Die Arbeit gliedert sich in sechs Teile: Nach einer einleitenden Gegenstandsbestimmung und einem Forschungsüberblick werden die Wortartenklassifizierung der klassischen chinesischen Philologie, die philologischen Grammatiken des 18. und 19. Jahrhunderts sowie die linguistischen und sprachtypologischen Charakterisierungen des Chinesischen im 19. Jahrhundert systematisch untersucht.

Zur theoretischen Einordnung der Befunde greift die Dissertation auf Newmeyers Unterscheidung zwischen formalen und funktionalen Erklärungsansätzen zurück. In wissenschaftsgeschichtlicher Perspektive zeigt sich, dass die Beschäftigung mit dem Chinesischen wiederholt zwischen strukturell-formalen und funktional, psychologisch bzw. kognitiv begründeten Zugängen oszillierte. Anstatt die Frage nach der „Grammatiklosigkeit“ des Chinesischen dichotom zu behandeln, wird deutlich, dass die entsprechenden Debatten eine Verschiebung und Erweiterung des Grammatikbegriffs widerspiegeln. Der scheinbare Widerspruch zwischen der Negation von Grammatik und ihrer impliziten Begründung erweist sich damit als perspektivisch bedingt und als Ausdruck unterschiedlicher, historisch situierter Versuche, die sprachliche Eigenart des Chinesischen innerhalb der jeweiligen theoretischen Rahmenbedingungen zu erfassen.