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  • Item type:Item,
    Fighting Poverty with Sheep in Armenia: The Role of Hope
    (2026) Weichbrodt, Louisa Joline
    Half of the world's population lives in poverty, yet eradicating poverty remains the first Sustainable Development Goal by 2030. Studies evaluating poverty traps and livestock often overlook the role of hope in their analyses, a factor that has recently been recognised as vital in combating poverty. Non-Governmental Organisations implement livestock transfer projects to help families escape poverty and restore hope. To understand the role of hope in these projects, a qualitative approach with interviews was employed, combined with observations of multidimensional poverty indicators to reveal participants' experiences of hope and changes in poverty. The study found that hope is essential for participants' responses to the project and, consequently, supports their exit from poverty. Levels of hope significantly influence perceptions and in turn, actions during participation. Moreover, individual hope was enhanced through livestock transfers, affecting goals, mood, and perception of the future. Subtle changes in multidimensional poverty related to housing and health expenditure planning were also observed. Additionally, development projects can nurture hope by improving mental health, addressing multiple dimensions of poverty, and actively supporting participants' aspirations. Policies can influence both external and internal constraints on poverty and foster hope: firstly, by providing structural grounds for hope; secondly, by informing about available opportunities; and thirdly, by encouraging and supporting aspirations. The government can use policies to promote hopefulness. The fact remains that people living in poverty are not necessarily hopeless. Further research could offer quantitative insights into hope within development contexts. Overall, recognising the role of hope is crucial for designing holistic and effective development projects.
  • Item type:Item,
    Trafficking and Sorting of Proteins to the Parasitophorous Vacuolar Membrane of Plasmodium falciparum: PfEXP1 as a Model
    (2026) Abbasi, Amin
    During the asexual blood stage of malaria infection, Plasmodium falciparum develops inside a membrane-bound compartment within the host red blood cell. The membrane surrounding this compartment, the parasitophorous vacuolar membrane (PVM), forms an important interface between parasite and host cell. In addition to exporting soluble effector proteins, the parasite must also direct a specific set of membrane proteins to the PVM. PfEXP1 is a well- established membrane protein of the PVM, but the sequence features that govern its trafficking to this membrane remain unclear. The aim of this thesis was therefore to identify PfEXP1 sequence features that contribute to its targeting to the PVM. To address this question, a panel of plasmid-expressed PfEXP1 variants was generated and analyzed by immunofluorescence microscopy in two parasite developmental stages. In parallel, a biochemical fractionation assay was used to compare whether the different variants behaved mainly as soluble or membrane-associated proteins. Across the construct panel, distal C-terminal truncations generally retained PVM-like localization under the assay conditions used. These variants showed staining patterns consistent with PVM localization and were enriched in the membrane-associated fraction, suggesting that they remained capable of stable membrane association. This indicates that the distal C-terminus is not a dominant determinant of this behavior. In contrast, disruption of the N-terminal region more often resulted in less distinct localization and weaker biochemical evidence for stable membrane association. The transmembrane domain replacement experiments further showed that not all membrane anchors behaved in the same way. Constructs combining the PfEXP1 N-terminal region with a parasite-derived transmembrane segment were more often consistent with PVM-like localization, whereas constructs containing artificial hydrophobic helices did not reproduce clear PVM localization even when flanked by PfEXP1-derived N- and C-terminal regions. These findings argue against a model in which hydrophobicity alone is sufficient for correct targeting. An important limitation of this study was the unexpected predominantly soluble behavior of the exogenous full-length PfEXP1 reference construct, indicating that construct architecture, including tag and linker context, can substantially affect the experimental readout. Taken together, the data support a model in which correct PfEXP1 targeting depends on N-terminal context acting together with an appropriate membrane anchor, whereas the distal C-terminal region appears broadly dispensable in this assay context. More broadly, this work highlights the need for follow-up experiments that directly resolve protein topology, particularly protease- protection assays.
  • Item type:Item,
    Essays on Monetary Policy, Non-Bank Financial Intermediation and Financial Stability
    (2025) Tiza Mimun, Anisa
    This dissertation provides an empirical examination of the relationship between monetary policy and non-bank financial intermediaries, commonly referred to as nonbanks.
  • Item type:Item,
    Microbiological and physical properties of biofilm-active PMMA bone cements in arthroplasty
    (2026) Humez, Martina Anneliese
    Periprosthetic joint infection (PJI) remains one of the most serious complications in arthroplasty, associated with high morbidity, mortality, and substantial socioeconomic burden. Antibiotic‑loaded bone cements (ALBCs) play a central role in both the prevention and treatment of PJI. In primary arthroplasty, they enable high local antibiotic concentrations at the implant-tissue interface, reducing early bacterial adhesion and lowering infection risk. In revision surgery, especially for established infection, ALBCs facilitate targeted antimicrobial delivery as cement spacers, while simultaneously providing mechanical stability for temporary or definitive fixation. Despite decades of clinical experience with ALBCs, fundamental questions remain incompletely understood: the selection of the most appropriate antimicrobial drugs for admixing to acrylic bone cements, pharmacokinetic carrier elution aspects, cement matrix interactions, antibiotic admixing methodology, and antibiotic dose limitations. Furthermore, it is not clear to which extent laboratory experiences can be transferred to the clinical setting. These knowledge gaps are particularly relevant in the context of rising antimicrobial resistances, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin‑resistant enterococci (VRE), for which therapeutic options are increasingly restricted. This cumulative dissertation integrates material science, microbiology, and translational in-vivo modelling to advance the evidence-based use of ALBCs in arthroplasty and revision surgery. Across four studies, the work systematically examines (i) the feasibility of formulating novel daptomycin-loaded poly-methyl-methacrylate (PMMA) cements for PJIs caused by vancomycin-resistant bacteria, (ii) the mechanical, chemical, and kinetic consequences of manual antibiotic admixing, (iii) the impact of the cement matrix on antibiotic release and long-term antimicrobial activity, and (iv) the translational antimicrobial efficacy of commercial single antibiotic-loaded bone cements (SALBCs) and dual-antibiotic loaded bone cements (DALBCs) in a validated Galleria mellonella implant infection model. A fifth investigation, presented at the EBJIS (European Bone & Joint Infection Society) congress and published as abstract, proposes an optimal daptomycin dosage and suitable PMMA cement matrix for spacer applications using the Galleria mellonella biofilm model. The results demonstrate that acrylic bone cements are not interchangeable materials: the polymer composition and additives, hydrophilicity, viscosity, sterilisation method and manufacturing process collectively determine the antibiotic elution, antimicrobial efficacy and mechanical stability. DALBCs consistently outperformed SALBCs in infection prevention, achieving superior antibiofilm effects, and providing markedly increased survival in larvae infected with multi-drug-resistant Staphylococcus aureus and Enterococcus faecalis. High local antibiotic concentrations generated by antibiotic elution from acrylic bone cements were able to overcome resistance phenotypes, emphasising the unique pharmacodynamic environment of ALBC. Systematic evaluation of manual admixing revealed that dry mixing of the powder in cartridge mixing devices did neither improve mechanical stability nor antibiotic release. It generated abrasive plastic debris capable of embedding into the cement highlighting previously unrecognised risks. Fractionated bowl mixing was identified as the only safe and reproducible preparation method when manual admixing is unavoidable. Cement brand was found to be a dominant predictor of antibiotic release, with the polymer composition in Palacos® cements consistently outperforming the one in Simplex® cements across all antibiotics tested. Finally, integrating in-vitro release kinetics with the Galleria mellonella biofilm model enabled the identification of 1.5 g daptomycin per 40 g PMMA (Palacos® R+G and Simplex® T) as the optimal risk-benefit balance between antimicrobial efficacy and mechanical integrity for cement spacers in VRE caused infections. In summary, this thesis provides a comprehensive evidence base for the rational selection, mixing, and clinical application of ALBCs. It clarifies the material dependent performance and establishes best‑practice standards for manual admixing, validates an efficient in-vivo screening platform for cement performance, and supports the development of future daptomycin-loaded DALBC formulations capable of addressing the growing challenge of multi-drug-resistant PJI. These results are of high clinical relevance for surgeons who deal with these difficult-to-treat orthopaedic infections.
  • Item type:Item,
    Spatiotemporal regulation of polar flagellar assembly, chemotaxis and c-di-GMP-dependent signaling in γ-proteobacteria
    (2026-03) Schmidt, Lisa Marie
    Bacterial motility is a fundamental trait that enables cells to explore their environment and respond to, as well as relocate to, more favorable growth conditions. In many species, motility is achieved by rotating flagellar filaments whose activity is controlled by the chemotaxis system, allowing bacteria to navigate along chemical gradients. In addition to this planktonic lifestyle, bacteria can transition to a sessile state, characterized by surface attachment and biofilm formation. This transition is generally regulated by intracellular second messenger molecules, such as c-di-GMP, with elevated levels promoting a sessile lifestyle by stimulating biofilm formation while simultaneously repressing motility. Consequently, coordination between chemotaxis and second messenger signaling is crucial for balancing motility and surface-associated growth in these bacteria. In this work, the spatiotemporal regulation of polar flagellar assembly, chemotaxis, and c-di-GMP- dependent signaling was investigated in species of the genera Shewanella and Pseudomonas. In S. putrefaciens, polar flagellar assembly was shown to depend on an interaction between the polar landmark protein FlhF and the flagellar C-ring component FliG, mediated by the N-terminal domain of FlhF, termed FID. Furthermore, FlhF was demonstrated to restrict FliG recruitment to the cell pole, through its simultaneous interaction with FliG and HubP. In addition, the function of the HubP homolog FimV was investigated in P. putida. FimV was shown to localize to the cell pole, depending on the presence of both a LysM-like domain and an immunoglobulin-like domain. While deletion of fimV did not affect flagellation, chromosome segregation, or pilus-mediated motility, FimV was required for correct positioning of the chemotaxis system and efficient swimming motility in P. putida. Domain exchange experiments between HubP and FimV from S. putrefaciens and P. putida revealed species-specific functions, indicating distinct adaptations to their respective environments. Moreover, the interaction between the histidine kinase CheA and the phosphodiesterase Pch was investigated in P. putida. Both proteins exhibited polar localization, and their interaction was shown to be mediated by the EAL domain of Pch and a specific region within the unstructured linker region of CheA. While the polar localization of Pch strongly depended on CheA, CheA localization depended on FlhF, PocB, and ParP, and, to a lesser extent, on FimV. Sequence conservation analysis revealed a specialized amino acid sequence of the Pch EAL domain compared to canonical EAL domains, as well as five highly conserved regions within the CheA linker region. This suggests an evolutionarily conserved interaction interface between CheA and Pch, linking chemotaxis and c-di-GMP signaling. Collectively, these results provide new insights into the spatiotemporal organization of flagellar assembly and chemotaxis signaling, highlighting the role of polar organizer proteins and signaling components in coordinating bacterial motility and transitions between motile and sessile states.