Abstract: Humanity feels the urge of shifting to a sustainable society more than at any other time in its history. Electrification of chemical industry plays a key role in this transition. The possibility of producing fertilizers from air using renewable electricity, and simultaneously, no greenhouse gas emission, resulted in an increasing interest toward plasma technology as a solution for electrification of a part of the chemical industry in the past few years. Additionally, the activation of nitrogen molecules by vibrational and electronic excitation reactions in plasma can lead to an energy-efficient process. Last but not least, the modularity (fast on/off characteristic) of plasma technology makes it capable of using intermittent renewable electricity on site for the production of fertilizers using air. All these advantages offered by plasma technology make it a potential solution for the on-site production of fertilizers in small and decentralized plants using air and renewable electricity, which leads to a considerable reduction in fertilizer production and transportation costs. However, industrialization of plasma-based NF suffers from several challenges, including challenges of plasma catalysis for the selective production of desired species, the high energy cost of plasma-based NF compared to current industrial processes, and the design and development of scaled up and energy-efficient plasma reactors for industrial purposes. In the framework of this thesis we have tried to add to the state-of-the-art (SOTA) in plasma-based NOx production and deal with its limitations using a combination of experimental and modelling work.

Abstract: Globally, incorporation of agricultural lands into the urban boundary has been a common phenomenon. Governments use various alternatives to access the required land, including land expropriation procedures, which refers to the compulsorily taking of land from the landholders without their consent by paying compensation. In Ethiopia, the urban population is growing rapidly which resulted into an increase in the demand for urban land for housing construction, public services provision, and infrastructure developments. As the Ethiopian constitution prohibits sale of landholders, governments, at various levels, have been expropriating land from the surrounding farmers to meet the demand for urban land. The general objective of this thesis is to improve the understanding of the impacts of local land deals for urbanization on socioeconomics of farmers and the environment. The findings of this thesis revealed that there are gaps in the current practices of land expropriation for urban expansion that should be improved. The results showed that the compensation paid to the affected farmers is found to be economically inappropriate, i.e., not enough to restore the affected farmers’ livelihoods, in contrast with the land laws that allows a compensation amount that would put previous land users in a better or the same wellbeing as before the land expropriation. In addition, it is indicated that the land expropriation process does not take into account the value of ecosystem services, which are benefits obtain from the land, and important for the wellbeing of the society. We conclude that while land expropriation is an important tool to obtain land from the landholders when it is needed for public purposes, the practices in the study area show it is adversely affecting the socioeconomics of farmers and the environment.

Abstract: Tidal marshes take up and release certain elements from and to the river water. Hence, they act as a filter, improving the estuarine water quality. This filtering function depends on the interaction between the marsh soil and water that infiltrates into the marsh platform at high tide and seeps out of the creek banks at low tide. In the past centuries, many tidal marshes disappeared due to large scale land reclamations, together with their associated ecosystem services. Nowadays, tidal marshes are increasingly restored on formerly embanked agricultural areas to regain these ecosystem services. Here, we studied the effect of historical agricultural land use on the contribution of restored tidal marshes to water quality improvement, and we investigated several solutions to stimulate the water quality improving function in newly restored tidal marshes. In restored tidal marshes, the soil is often compacted due to the historical agricultural land use, leading to a reduced organic matter content and micro- and macroporosity. In this compacted soil, groundwater flow is hindered, leading to a more waterlogged soil and reduced groundwater dynamics in the restored marsh as compared to a natural marsh. The depth of groundwater drainage and the groundwater flow velocity have important implications for the processes that contribute to water quality improvement, e.g. removal of nitrogen, phosphorus retention and silica cycling. Where groundwater drains deeper, i.e. in the vicinity of tidal creeks and in a more porous soil, these processes are promoted. We suggest that, in newly restored tidal marshes, the soil porosity can be increased by amending the soil (e.g. with organic matter), and the distance to the nearest tidal creek can be reduced by creek excavation. Numerical modelling showed that the largest gain in groundwater dynamics and seepage was attained when both measures were applied together. The effect of organic soil amendments on groundwater dynamics and nutrient cycling was further explored in a large scale in situ mesocosm experiment. Where the soil was amended, groundwater drained deeper and nitrogen removal increased. For new tidal marsh restoration projects, we advise to conduct an explorative soil study. When the soil is heavily compacted, design measures, such as creek initiation and organic soil amendments can be applied to jumpstart the contribution to water quality improvement of newly restored tidal marshes.

Abstract: Pancreatic ductal adenocarcinoma (PDAC) and glioblastoma multiforme (GBM) are two of the most malignant solid tumor types with poor survival rates, which underscore the urgency of novel and efficacious treatment strategies. Within the last decade, immunotherapy has been established as a breakthrough in cancer therapy. This mainly has been driven by the clinical data and approval associated with several immune checkpoint inhibitors (e.g. anti-CTLA-4 and anti-PD-1/L1). Despite the clinical benefit in specific tumor types, these inhibitors have not yet fulfilled their promise in low immunogenic tumors such as PDAC and GBM. Oxidative stress in cancer cells due to elevated reactive oxygen species (ROS) and an inability to balance intracellular redox state has recently been highlighted as promising target for anticancer treatment strategies with possible immunogenic effects. In this PhD dissertation, I investigated novel oxidative stress-mediated treatment approaches to target PDAC and GBM and to enhance immunogenicity by inducing immunogenic cell death (ICD). In the first part of this thesis (chapter 2), I reviewed the mechanistic responses of cancer cells towards different oxidative stress-inducing treatment strategies and their immunomodulating effects. The resulting literature demonstrated that different exogenous and endogenous ROS-inducing therapies show direct and indirect immunomodulating effects, which can be either immunostimulatory or immunosuppressive. One of the indirect immunostimulatory effects of the ROS-mediating therapies is the capacity of inducing immunogenic cell death (ICD) in tumor cells, which can increase the immunogenicity and consequently can trigger an antitumoral immune response. In chapter 3, I investigated a novel exogenous ROS-inducing treatment method, namely cold atmospheric plasma, to determine the therapeutic and ICD-inducing effects in PDAC, in vitro. I revealed that plasma-treated PBS (pPBS) has the potential to induce ICD in pancreatic cancer cells (PCCs) and to reduce the immunosuppressive tumor microenvironment (TME) by attacking the tumor supportive pancreatic stellate cells (PSCs). Although the cell death induced in PSCs was non-immunogenic as seen by the lack of danger-associated molecular patterns (DAMPs) emission and DC activation, I showed that pPBS could disrupt the physical barrier and lower the immunosuppressive secretion profile (lower TGF-β) of PSCs. In contrast, DAMPs were released by PCCs after treatment with pPBS which resulted in activation and maturation of DCs and a more immunostimulatory secretion profile (higher TNF-α, IFN-γ). Hence, indirect plasma treatment via pPBS has the potential to enhance immunogenicity in PDAC by triggering ICD and by attacking the immunosuppressive PSCs. Tumor cells can evolve adaptation mechanisms to protect themselves against intrinsic oxidative stress by upregulation of pro-survival molecules and their antioxidant defense system to maintain the redox balance. As such, tumor cells can become resistant towards exogenous ROS-inducing therapies, like plasma. Dual targeting of the redox balance of tumor cells by increasing exogenous levels of ROS and inhibiting the antioxidant defense system can maximally exploit ROS-mediated cell death mechanisms as therapeutic anticancer strategy. In this regard, cold atmospheric plasma was combined with auranofin, a thioredoxin reductase inhibitor, in GBM (chapter 4). A synergistic effect was shown after this combination treatment in 2D and 3D, however, in 3D only high concentrations of auranofin synergized with plasma treatment. I confirmed a ROS-mediated response after combination treatment, which was able to induce distinct cell death mechanisms, specifically apoptosis and ferroptosis. Additionally, the auranofin and plasma combined treatment strategy induced cell death, which resulted in an increased release of DAMPs. Together with the observed DC maturation, these results indicates the potential increase in immunogenicity, though, the phagocytotic capacity of DCs was inhibited by auranofin. In chapter 5, I evaluated this promising oxidative stress combination therapy in GBM, in vivo. A decrease in tumor kinetics and an increased survival in GBM-bearing mice was observed when auranofin was sequentially combined with direct plasma treatment. No T cell infiltration was observed after auranofin monotherapy. However, further characterization of the TME after the combination therapy is necessary to provide more insight in the immunogenic effects in vivo. In conclusion, this PhD dissertation comprises novel and important therapeutic and immunogenic insights in cold atmospheric plasma and auranofin as promising oxidative stress-mediated treatment strategies for low immunogenic tumors, like PDAC and GBM. These preclinical results provide a solid basis for future research towards combinations with immunotherapeutic approaches.