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Cardiovascular diseases are the main cause of death worldwide, and their prevalence is expected to rise in the coming years. Polymer-based artificial replacements have been widely used for the treatment of cardiovascular diseases. Coagulation and thrombus formation on the interfaces between the materials and the human physiological environment are key issues leading to the failure of the medical device in clinical implantation. The surface properties of the materials have a strong influence on the protein adsorption and can direct the blood cell adhesion behavior on the interfaces. Furthermore, implant-associated infections will be induced by bacterial adhesion and subsequent biofilm formation at the implantation site. Thus, it is important to improve the hemocompatibility of an implant by altering the surface properties. One of the effective strategies is surface passivation to achieve protein/cell repelling ability to reduce the risk of thrombosis.
This thesis consists of synthesis, functionalization, sterilization, and biological evaluation of bulk poly(glycerol glycidyl ether) (polyGGE), which is a highly crosslinked polyether-based polymer synthesized by cationic ring-opening polymerization. PolyGGE is hypothesized to be able to resist plasma protein adsorption and bacterial adhesion due to analogous chemical structure as polyethylene glycol and hyperbranched polyglycerol. Hydroxyl end groups of polyGGE provide possibilities to be functionalized with sulfates to mimic the anti-thrombogenic function of the endothelial glycocalyx.
PolyGGE was synthesized by polymerization of the commercially available monomer glycerol glycidyl ether, which was characterized as a mixture of mono-, di- and tri-glycidyl ether. Cationic ring opening-polymerization of this monomer was carried out by ultraviolet (UV) initiation of the photo-initiator diphenyliodonium hexafluorophosphate. With the increased UV curing time, more epoxides in the side chains of the monomers participated in chemical crosslinking, resulting in an increase of Young’s modulus, while the value of elongation at break of polyGGE first increased due to the propagation of the polymer chains then decreased with the increase of crosslinking density. Eventually, the chain propagation can be effectively terminated by potassium hydroxide aqueous solution. PolyGGE exhibited different tensile properties in hydrated conditions at body temperature compared to the values in the dry state at room temperature. Both Young’s modulus and values of elongation at break were remarkably reduced when tested in water at 37 °C, which was above the glass transition temperature of polyGGE. At physiological conditions, entanglements of the ployGGE networks unfolded and the free volume of networks were replaced by water molecules as softener, which increased the mobility of the polymer chains, resulting in a lower Young’s modulus.
Protein adsorption analysis was performed on polyGGE films with 30 min UV curing using an enzyme-linked immunosorbent assay. PolyGGE could effectively prevent the adsorption of human plasma fibrinogen, albumin, and fibronectin at the interface of human plasma and polyGGE films. The protein resistance of polyGGE was comparable to the negative controls: the hemocompatible polydimethylsiloxane (PDMS), showing its potential as a coating material for cardiovascular implants. Moreover, antimicrobial tests of bacterial activity using isothermal microcalorimetry and the microscopic image of direct bacteria culturing demonstrated that polyGGE could directly interfere biofilm formation and growth of both Gram-negative and antibiotic-resistant Gram-positive bacteria, indicating the potential application of polyGGE for combating the risk of hospital-acquired infections and preventing drug-resistant superbug spreading.
To investigate its cell compatibility, polyGGE films were extracted by different solvents (ethanol, chloroform, acetone) and cell culture medium. Indirect cytotoxicity tests showed extracted polyGGE films still had toxic effects on L929 fibroblast cells. High-performance liquid chromatography/electrospray ionization mass spectrometry revealed the occurrence of organochlorine-containing compounds released during the polymer-cell culture medium interaction. A constant level of those organochlorine-containing compounds was confirmed from GGE monomer by a specific peak of C-Cl stretching in infrared spectra of GGE. This is assumed to be the main reason causing the increased cell membrane permeability and decreased metabolic activity, leading to cell death. Attempts as changing solvents were made to remove toxic substances, however, the release of these small molecules seems to be sluggish. The densely crosslinked polyGGE networks can possibly contribute to the trapping of organochlorine-containing compounds. These results provide valuable information for exploring the potentially toxic substances, leaching from polyGGE networks, and propose a feasible strategy for minimizing the cytotoxicity via reducing their crosslinking density.
Sulfamic acid/ N-Methyl-2-pyrrolidone (NMP) were selected as the reagents for the sulfation of polyGGE surfaces. Fourier transform attenuated total reflection infrared spectroscopy (ATR-FT-IR) was used to monitor the functionalization kinetics and the results confirmed the successful sulfate grafting on the surface of polyGGE with the covalent bond -C-O-S-. X-ray photoelectron spectroscopy was used to determine the element composition on the surface and the cross-section of the functionalized polyGGE and sulfation within 15 min guarantees the sulfation only takes place on the surface while not occurring in the bulk of the polymer. The concentration of grafted sulfates increased with the increasing reaction time. The hydrophilicity of the surface of polyGGE was highly increased due to the increase of negatively charged end groups. Three sterilization techniques including autoclaving, gamma irradiation, and ethylene oxide (EtO) sterilization were used for polyGGE sulfates. Results from ATR-FT-IR and Toluidine Blue O quantitative assay demonstrated the total loss of the sulfates after autoclave sterilization, which was also confirmed by the increased water contact angle. Little influence on the concentration of sulfates was found for gamma-irradiated and autoclaving sterilized polyGGE sulfates. To investigate the thermal influence on polyGGE sulfates, one strategy was to use poly(hydroxyethyl acrylate) sulfates (PHEAS) for modeling. The thermogravimetric analysis profile of PHEAS demonstrated that sulfates are not thermally stable independent of the substrate materials and decomposition of sulfates occurs at around 100 °C. Although gamma irradiation also showed little negative effect on the sulfate content, the color change in the polyGGE sulfates indicates chemical or physical change might occur in the polymer. EtO sterilization was validated as the most suitable sterilization technique to maintain the chemical structure of polyGGE sulfates.
In conclusion, the conducted work proved that bulk polyGGE can be used as an antifouling coating material and shows its antimicrobial potential. Sulfates functionalization can be effectively realized using sulfamic acid/NMP. EtO sterilization is the most suitable sterilization technique for grafted sulfates. Besides, this thesis also offers a good strategy for the analysis of toxic leachable substances using suitable physicochemical characterization techniques. Future work will focus on minimizing/eliminating the release of toxic substances via reducing the crosslinking density. Another interesting aspect is to study whether grafted sulfates can meet the need for anti-thrombogenicity.
The Turkish language in diaspora is in process of change due to different language constellations of immigrants and the dominance of majority languages. This led to a great interest in various research areas, particularly in linguistics. Against this background, this study focuses on developmental change in the use of adverbial clause-combining constructions in Turkish-German bilingual students’ oral and written text production. It illustrates the use of non-finite constructions and some unique alternative strategies to express adverbial relations with authentic examples in Turkish and German. The findings contribute to a better understanding of how bilingual competencies vary in expressing adverbial relations depending on language contact and extra-linguistic factors.
In the automotive industry, suppliers from the consumer electronics and high-tech industry are becoming increasingly relevant, for example in the context of automated vehicles. The carmakers’ purchasing organizations need to understand the power constellation in negotiations with these new suppliers, since negotiating power is the greatest lever for influencing the outcome of negotiations. This study analyzes the importance of organizational sources of power and their interplay with the products’ degree of innovation.
The morphogenesis of sessile plants is mainly driven by directional cell growth and cell division. The organization of their cytoskeleton and the mechanical properties of the cell wall greatly influence morphogenetic events in plants. It is well known that cortical microtubules (CMTs) contribute to directional growth by regulating the deposition of the cellulose microfibrils, as major cell wall fortifying elements. More recent findings demonstrate that mechanical stresses existing in cells and tissues influence microtubule organization. Also, in dividing cells, mechanical stress directions contribute to the orientation of the new cell wall. In comparison to the microtubule cytoskeleton, the role of the actin cytoskeleton in regulating shoot meristem morphogenesis has not been extensively studied.
This thesis focuses on the functional relevance of the actin cytoskeleton during cell and tissue scale morphogenesis in the shoot apical meristem (SAM) of Arabidopsis thaliana. Visualization of transcriptional reporters indicates that ACTIN2 and ACTIN7 are two highly expressed actin genes in the SAM. A link between the actin cytoskeleton and SAM development derives from the observation that the act2-1 act7-1 double mutant has abnormal cell shape and perturbed phyllotactic patterns. Live-cell imaging of the actin cytoskeleton further shows that its organization correlates with cell shape, which indicates a potential role of actin in influencing cellular morphogenesis.
In this thesis, a detailed characterization of the act2-1 act7-1 mutant reveals that perturbation of actin leads to more rectangular cellular geometries with more 90° cell internal angles, and higher incidences of four-way junctions (four cell boundaries intersecting together). This observation deviates from the conventional tricellular junctions found in epidermal cells. Quantitative cellular-level growth data indicates that such differences in the act2-1 act7-1 mutant arise due to the reduced accuracy in the placement of the new cell wall, as well as its mechanical maturation. Changes in cellular morphology observed in the act2-1 act7-1 mutant result in cell packing defects that subsequently compromise the flow of information among cells in the SAM.
Throughout their lifetime plants need to adapt to temperature changes. Plants adapt to nonfreezing cold temperatures in a process called cold priming (cold acclimation) and lose the acquired freezing tolerance during warmer temperatures through deacclimation. The alternation of both processes is essential for plants to achieve optimal fitness in response to different temperature conditions. Cold acclimation has been extensively studied, however, little is known about the regulation of deacclimation. This thesis elucidates the process of deacclimation on a physiological and molecular level in Arabidopsis thaliana. Electrolyte leakage measurements during cold acclimation and up to four days of deacclimation enabled the identification of four knockout mutants (hra1, lbd41, mbf1c and jub1) with a slower rate of deacclimation compared to the wild type. A transcriptomic study using RNA-Sequencing in A. thaliana Col-0, jub1 and mbf1c identified the importance of the inhibition of stress responsive and Jasmonate-ZIM-domain genes as well as the regulation of cell wall modifications during deacclimation. Moreover, measurements of alcohol dehydrogenase activity and gene expression changes of hypoxia markers during the first four days of deacclimation evidently showed that a hypoxia response is activated during deacclimation. Epigenetic regulation was observed to be extensively involved during cold acclimation and 24 h of deacclimation in A. thaliana. Further, both deacclimation studies showed that the previous hypothesis that heat stress might play a role in early deacclimation, is not likely. A number of DNA- and histone demethylases as well as histone variants were upregulated during deacclimation suggesting a role in plant memory. Recently, multiple studies have shown that plants are able to retain memory of a previous cold stress even after a week of deacclimation. In this work, transcriptomic and metabolomic analyses of Arabidopsis during 24 h of priming (cold acclimation) and triggering (recurring cold stress after deacclimation) revealed a uniquely significant and transient induction of DREB1D, DREB1E and DREB1F transcription factors during triggering contributing to fine-tuning of the second cold stress response. Furthermore, genes encoding Late Embryogenesis Abundant (LEA) and antifreeze proteins and proteins detoxifying reactive oxygen species were higher induced during late triggering (24 h) compared to primed samples, while cell wall remodelers of the class xyloglucan endotransglucosylase/hydrolase were early responders of triggering. The high induction of cell wall remodelers during deacclimation as well as triggering proposes that these proteins play an essential role in the stabilization of the cells during growth as well as the response to recurring stresses. Collectively this work gives new insights on the regulation of deacclimation and cold stress memory in A. thaliana and opens the door to future targeted studies of essential genes in this process.
Afropolitan Encounters
(2022)
Afropolitan Encounters: Literature and Activism in London and Berlin explores what Afropolitanism does. Mobile people of African descent use this term to address their own lived realities creatively, which often includes countering stereotypical notions of being African. Afropolitan practices are enormously heterogeneous and malleable, which constitutes its strengths and, at the same time, creates tensions.
This book traces the theoretical beginnings of Afropolitanism and moves on to explore Afropolitan practices in London and Berlin. Afropolitanism can take different forms, such as that of an identity, a political and ethical stance, a dead–end road, networks, a collective self–care practice or a strategic label. In spite of the harsh criticism, Afropolitanism is attractive for people to deal with the meanings of Africa and Africanness, questions of belonging, equal rights and opportunities.
While not a unitary project, the vast variety of Afropolitan practices provide approaches to contemporary political problems in Europe and beyond. In this book, Afropolitan practices are read against the specific context of German and British colonial histories and structures of racism, the histories of Black Europeans, and contemporary right–wing resurgence in Germany and England, respectively.
The aim of this work is the study of silica Arrayed Waveguide Gratings (AWGs) in the context of applications in astronomy. The specific focus lies on the investigation of the feasibility and technology limits of customized silica AWG devices for high resolution near-infrared spectroscopy. In a series of theoretical and experimental studies, AWG devices of varying geometry, foot-print and spectral resolution are constructed, simulated using a combination of a numerical beam propagation method and Fraunhofer diffraction and fabricated devices are characterized with respect to transmission efficiency, spectral resolution and polarization sensitivity. The impact of effective index non-uniformities on the performance of high-resolution AWG devices is studied numerically. Characterization results of fabricated devices are used to extrapolate the technology limits of the silica platform. The important issues of waveguide birefringence and defocus aberration are discussed theoretically and addressed experimentally by selection of an appropriate aberration-minimizing anastigmatic AWG layout structure. The drawbacks of the anastigmatic AWG geometry are discussed theoretically. From the results of the experimental studies, it is concluded that fabrication-related phase errors and waveguide birefringence are the primary limiting factors for the growth of AWG spectral resolution. It is shown that, without post-processing, the spectral resolving power is phase-error-limited to R < 40, 000 and, in the case of unpolarized light, birefringence-limited to R < 30, 000 in the AWG devices presented in this work. Necessary measures, such as special waveguide geometries and post-fabrication phase error correction are proposed for future designs. The elimination of defocus aberration using an anastigmatic AWG geometry is successfully demonstrated in experiment. Finally, a novel, non-planar dispersive in-fibre waveguide structure is proposed, discussed and studied theoretically.
Receptors predominantly expressed on tumor cells represent one of the key prerequisites of targeted radiotherapy. The gastric inhibitory polypeptide receptor (GIPR) has emerged as a promising target due to its substantial overexpression in neuroendocrine neoplasms (NENs) and virtual absence in healthy tissues (Waser 2012). So far, only radiolabeled peptides targeting the somatostatin receptor 2 (SSTR2) are approved for targeted radiotherapy of inoperable, metastatic NENs.
The aim of this thesis was to develop highly affine GIPR tracers for targeted radiotherapy by continuous in vitro and in vivo characterization of peptide sequence modifications. It was hypothesized that a GIPR antagonist might increase the sensitivity to detect GIPR-positive tumors relative to the agonist GIP(1-30), as shown for SSTR2 tracers (Reubi 2017). Further comparison to the SSTR2 agonist and antagonist (DOTATATE, JR11) should allow compound ranking regarding their ability to detect NENs.
The novel GIPR-targeting antagonists were conjugated to DOTA, enabling complexation of diagnostic (e. g. 111In) and therapeutic radionuclides (e. g. 177Lu). Among the high number of compounds screened, 3BP-3775 proved to be the most promising candidate for further preclinical and clinical development. High GIPR affinity and long receptor residence time in vitro were reflected in strong tumor uptake and retention in vivo. Low initial kidney accumulation and fast subsequent clearance represented a major advantage relative to previously described GIPR-targeting molecules (Gourni 2014). Furthermore, administration of 177Lu-3BP-3775 demonstrated for the first time strong therapeutic efficacy of a GIPR-targeting compound. In vitro receptor autoradiography with 111In-3BP-3626 (GIPR antagonist) demonstrated up to 6-fold higher signals in gastroenteropancreatic and bronchial NENs, relative to the clinically utilized SSTR2 agonist 111In-DOTATATE. Both receptor antagonists, however, revealed similar signal strength. In contrast to 111In-JR11, 111In-3BP-3626 showed no binding to non-target tissues, which led to higher tumor-to-background ratios for 111In-3BP-3626. Signal strength of the GIPR agonist 111In-GIP(1-30) was close to background in all investigated tumor samples. The ranking of compounds according to their ability to detect NENs based on autoradiographic signal intensities was determined to be: 111In-3BP-3626 ~ 111In-JR11> 111In-DOTATATE > 111In GIP(1-30).
In summary, this thesis proposes the application of the GIPR antagonist 3BP-3775 for a targeted radiotherapy in GEP- and bronchial NENs.
The prevalence of depression and anxiety is increased in obese patients compared to healthy humans, which is partially due to a shared pathogenesis, including insulin resistance and inflammation. These factors are also linked to intestinal dysbiosis. Additionally, the chronic consumption of diets rich in saturated fats results in body weight gain, hormonal resistances and unfavorable changes in the microbiome composition. The intake of Lactobacilli has already been shown to improve dysbiosis along with metabolism and mood. Yet, the beneficial role and the underlying mechanism of Lactobacillus rhamnosus GG (LGG) to improve emotional behavior in established diet-induced obese conditions are, so far, unknown. To characterize the role of LGG in diet-induced obesity, female and male C57BL/6N mice were fed a semi-synthetic low-fat diet (LFD, 10 % kcal from fat) or a conventional high-fat diet (HFD, 45 % kcal from fat) for initial 6 weeks, which was followed by daily oral gavage of vehicle or 1x10^8 CFU of LGG until the end of the experiment. Mice were subjected to basic metabolic and extensive behavioral phenotyping, with a focus on emotional behavior. Moreover, composition of cecal gut microbiome, metabolomic profile in plasma and cerebrospinal fluid was investigated and followed by molecular analyses. Both HFD-feeding and LGG application resulted in sex-specific differences. While LGG prevented the increase of plasma insulin, adrenal gland weight and hyperactivity in diet-induced obese female mice, there was no regulation of anxiodepressive-like behavior. In contrast, metabolism of male mice did not benefit from LGG application, but strikingly, LGG decreased specifically depressive-like behavior in the Mousetail Suspension Test which was confirmed by the Splash Test characterizing motivation for ’self-care’. The microbiome analysis in male mice revealed that HFD-feeding, but not LGG application, altered cecal microbiome composition, indicating a direct effect of LGG on behavioral regulation. However, in female mice, both HFD-feeding and LGG application resulted in changes of microbiome composition, which presumably affected metabolism. Moreover, as diet-induced obese female mice unexpectedly did not exhibit anxiodepressive-like behavior, follow-up analyses were conducted in male mice. Here, HFD-feeding significantly altered abundance of plasma lipids whereas LGG decreased branched chain amino acids which associated with improved emotional behavior. In nucleus accumbens (NAcc) and VTA/SN, which belong to the dopaminergic system, LGG restored HFD-induced decrease of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, on gene expression level. Lastly, transcriptome analysis in the NAcc identified gene expression of cholecystokinin as a potential mediator of the effect of LGG on HFD-induced emotional alterations. In summary, this thesis revealed the beneficial effects of LGG application on emotional alterations in established diet-induced obesity. Furthermore, both HFD-feeding and LGG treatment exhibited sex-specific effects, resulting in metabolic improvements in female mice while LGG application mitigated depressive-like behavior in obese male mice along with a molecular signature of restored dopamine synthesis and neuropeptide signaling.
Heat stress (HS) is one of the most common abiotic stresses, frequently affecting plant growth and crop production. With its fluctuating nature, HS episodes are frequently interspersed by stress-free intervals. Plants can be primed by HS, allowing them to survive better a recurrent stress episode. A memory of this priming can be maintained during stress-free intervals and this memory is closely correlated with transcriptional memory at several HS-inducible loci. This transcriptional memory is evident from hyper-induction of a locus upon a recurrent HS. ASCORBATE PEROXIDASE 2 (APX2) shows such hyper-induction upon recurring HS, however, the molecular basis of this transcriptional memory is not understood. Previous research showed that the HSinduced transcriptional memory at APX2 can last for up to seven days, and that it is controlled by cis-regulatory elements within the APX2 promoter.
To identify regulators involved in HS transcriptional memory, an unbiased forward genetic screening using EMS mutated seeds of pAPX2::LUC was performed from this screen. Two EMS mutants with affected transcriptional memory of LUC were identified. I confirmed that both two EMS mutants resulted from the gene mutations of HISTONE ACETYLTRANSFERASE 1 (HAC1). Besides pAPX2::LUC, the HS-induced transcription of other HS memory genes were also affected in hac1 mutants. Moreover, HAC1 may promote HS transcriptional memory by acetylating promoters of HS memory genes.
On the other hand, to identify cis-regulatory elements that are required for transcriptional memory of APX2, I performed promoter analysis of the four conserved HSEs identified within a functional APX2 promoter. I found out that one of the HSEs (HSE1) is necessary for both HS-induced APX2 transcription and transcriptional memory, while another one of HSEs (HSE2) is important for HS-induced APX2 transcriptional memory. I also found out that the HSE1 itself (with 10 bp of flanking sequence) is sufficient to confer HS-induced APX2 transcriptional memory, and HSE1 is also necessary for HSFA2 to bind on APX2 promoter and activate APX2 transcription. The findings will provide important clues for the molecular mechanism of transcriptional memory and will enable engineering of enhanced stress tolerance in crops.
Novel algorithms for prediction of protein complexes from protein-protein interacton networks
(2022)
Uncovering the interplay between nutrient availability and cellulose biosynthesis inhibitor activity
(2022)
All plant cells are surrounded by a dynamic, carbohydrate-rich extracellular matrix known as the cell wall. Nutrient availability affects cell wall composition via uncharacterized regulatory mechanisms, and cellulose deficient mutants develop a hypersensitive root response to growth on high concentrations of nitrate. Since cell walls account for the bulk of plant biomass, it is important to understand how nutrients regulate cell walls. This could provide important knowledge for directing fertilizer treatments and engineering plants with higher nutrient use efficiency. The direct effect of nitrate on cell wall synthesis was investigated through growth assays on varying concentrations of nitrate, measuring cellulose content of roots and shoots, and assessing cellulose synthase activity (CESA) using live cell imaging with spinning disk confocal microscopy. A forward genetic screen was developed to isolate mutants impaired in nutrient-mediated cell wall regulation, revealing that cellulose biosynthesis inhibitor (CBI) activity is modulated by nutrient availability. Various non-CESA mutants were isolated that displayed CBI resistance, with the majority of mutations causing perturbation of mitochondria-localized proteins. To investigate mitochondrial involvement, the CBI mechanism of action was investigated using a reverse genetic screen, a targeted pharmacological screen, and -omics approaches. The results generated suggest that CBI-induced cellulose inhibition is due to off-target effects. This provides the groundwork to investigate uncharacterized processes of CESA regulation and adds valuable knowledge to the understanding of CBI activity, which could be harnessed to develop new and improved herbicides.
Despite the importance of negotiations in companies and their contribution to strategic corporate planning, researchers have not yet focused on assessing the development of negotiations in the future. To broaden the field of futures research in negotiations and to provide empirical guidance about strategic business decisions to negotiators and managers, this work exploratively investigates the future of negotiations. The impact of trends on negotiations and negotiation behavior, as well as the development of future negotiation scenarios are therefore examined. Moreover, the preparation of negotiators for the future is analyzed and how effective negotiation teaching can be designed to improve negotiation performance.
Under the in vivo condition, a cell is continually interacting with its surrounding microenvironment, which is composed of its neighboring cells and the extracellular matrix (ECM). These components generate and transmit the microenvironmental signals to regulate the fate and function of the target cells. Except the signals from the microenvironment, stimuli from the ambient environment, such as temperature changes, also play an important in modulating the cell behaviors, which are considered as regulators from the macroenvironment. In this regard, recapitulation of these environmental factors to steer cell function will be of crucial importance for therapeutic purposes and tissue regeneration. Although the role of a variety of environmental factors has been evaluated, it is still challenging to identify and provide the appropriate factors, which are required for optimizing the survival of cells and for ensuring effective cell functions.
Thus, in vitro recreating the environmental factors that are present in the extracellular environment would help to understand the mechanism of how cells sense and process those environmental signals. In this context, this thesis is aimed to harness these environmental parameters to guide cell responses. Here, human induced pluripotent stem cells (hiPSCs) and human keratinocytes (KTCs), HaCaT cells, were used to investigate the impact of signals from the microenvironment or stimuli from the macroenvironment.
Firstly, polydopamine (PDA) or chitosan (CS) modifications were applied to generate different substrate surfaces for hiPSCs and KTCs (Chapter 4 to Chapter 6). Our results showed that the PDA modification was efficient to increase the cell-substrate adhesion and consequently promoted cell spreading. While CS modification was able to decrease the cell-substrate adhesion and enhance the cell-cell interaction, which enabled the morphology shift from monolayered cells to multicellular spheroids. The quantitative result was acquired using the atomic force microscopy (AFM)-based single-cell force spectroscopy. The balance between the cell-substrate and cell-cell adhesion yielded a net force, which determined the preference of the cell to adhere to its neighboring cells or to the substrate. The difference in the adhesive behaviors further affected the cellular function, such as the proliferation and differentiation potential of both hiPSCs and HaCaT cells.
Next, the cyclic temperature changes (ΔT) were selected here to study the influence of macroenvironmental stimuli on hiPSCs and KTCs (Chapter 7 and Chapter 8). The macroenvironmental temperature ranging from 10.0 ± 0.1 °C to 37.0 ± 0.1 °C was achieved using a thermal chamber equipped with a temperature controller. This temperature range was selected to explore the responses of hiPSCs to the extreme environments, while a temperature variation between 25.0 ± 0.1 °C and 37.0 ± 0.1 °C was applied to mimic the ambient temperature variations experienced by the skin epithelial KTCs. The ΔT led to cell stiffening in both hiPSCs and HaCaT cells in a cytoskeleton-dependent manner, which was measured by AFM. Specifically, in hiPSCs, the cell stiffening was resulted from the rearrangement of the actin skeleton; in HaCaT cells, was due to the difference of the Keratin (KRT) filaments. Except for inducing cell hardening, ΔT also caused differences in the protein expression profiles in hiPSCs or HaCaT cells, compared to those without ΔT treatment, which might be attributed to the alterations in their cytoskeleton structures.
To sum up, the results of the thesis demonstrated how individual factors from the micro-/macro-environment can be harnessed to modulate the behaviors of hiPSCs and HaCaT cells. Engineering the microenvironmental cues using surface modification and exploiting the macroenvironmental stimuli through temperature control were identified as precise and potent approaches to steer hiPSC and HaCaT cell behaviors. The application of AFM served as a non-invasive and real-time monitoring platform to trace the change in cell topography and mechanics induced by the environmental signals, which provide novel insights into the cell-environment interactions.
The Annamites mountain range of Southeast Asia which runs along the border of Viet Nam and Laos is an important biodiversity hotspot with high levels of endemism. However, that biodiversity is threatened by unsustainable hunting, and many protected areas across the region have been emptied of their wildlife. To better protect the unique species in the Annamites, it is crucial to have a better understanding of their ecology and distribution. Additionally, basic genetic information is needed to provide conservation stakeholders with essential information to facilitate conservation breeding and counteract the illegal wildlife trade. To date, this baseline information is lacking for many Annamites species.
This thesis aims to assess the effectiveness of using non-invasive collection methods, i.e. camera-trap surveys and leech-derived wildlife host DNA, in order to improve and enhance our understanding of ecology, distribution, and genetic diversity of the Annamites terrestrial mammals.
In chapter 1, we analysed data from a systematic landscape camera-trap survey using single-species occupancy models to assess the ecology and distribution of two little-known Annamite endemics, the Annamite dark muntjac (Muntiacus rooseveltorum / truongsonensis) and Annamite striped rabbit (Nesolagus timminsi), in multiple protected areas across the Annamites. This chapter provided the first in-depth information on their ecology, as well as distribution patterns at large spatial scales. Most notably, we found that the Annamite dark muntjac was predominantly found at higher elevations, while responses to elevation varied among study areas for the Annamite striped rabbit. We estimated occupancy probabilities for both endemics by using their responses to environmental and anthropogenic influences and used this information to make recommendations for targeted conservation actions. We discuss how the approach we used for these two Annamites endemics can be expanded for other little-known and threatened species in other tropical regions.
As is the case with ecology and distribution, very little is known about the genetic diversity of the Annamite striped rabbit and other mammals of the Annamites. This poor understanding is mainly attributed to the lack of a comprehensive DNA sample collection that covers the species’ entire distribution range, which is believed to be a consequence of the low density of mammals or the remoteness of species’ habitat. In order to overcome the difficulties when trying to collect DNA samples from elusive mammals, we applied invertebrate-derived DNA (iDNA) sampling via hematophagous leeches to indirectly obtain genetic materials of their terrestrial host mammals.
In chapter 2, leech-derived DNA was used to study the genetic diversity of the Annamite striped rabbit population. By analysing the DNA extracted from leech samples collected at multiple study areas of the central Annamites, we found a genetic variation with five haplotypes among nine obtained sequences. Despite this diversity, we found no clear phylogeographic pattern among the lagomorph’s populations in central Annamites. The findings have direct conservation implications for the species, as local stakeholders are currently establishing a conservation rescue and breeding facility for Annamite endemic species. Thus our results suggested that Annamite striped rabbits from multiple protected areas in central Annamites can be used as founders for the breeding program.
In chapter 3, the genetic material of six mammals, which are frequently found in Indochina's illegal wildlife trade, was extracted from leeches collected at six study sites across the Anamites. Species-specific genetic markers were used to obtain DNA fragments that were analysed together with Genbank reference sequences from other parts of the species’ distribution range. Our results showed that invertebrate-derived DNA can be used to fill the sampling gaps and provide genetic reference data that is needed for conservation breeding programmes or to counteract the illegal wildlife trade.
Overal, this dissertation provides the first insights in the ecology, distribution, and genetics of rare and threatened species of the Annamites by utilising camera traps and leech-derived DNA as two non-invasive collection methods. This information is essential for improving conservation efforts of local stakeholders and managers, especially for the Annamite endemics. Results in this dissertation also show the effectiveness of both non-invasive methods for studying terrestrial mammals at a landscape level. By expanding the application of these methods to other protected areas across the Annamites, we will further our understanding of ecology, distribution, and genetics of Annamite endemics. With such landscape-scale surveys, we are able to provide stakeholders with an overview of the current status of wildlife in the Annamites which supports efforts to protect these secretive species from illegal hunting and thus their extinction.
Development of functionalized waterborne coatings for the production of multifunctional microapsules
(2022)
The Clash of the Images
(2022)
In everyday life, we take there to be ordinary objects such as persons, tables, and stones bearing certain properties such as color and shape and standing in various causal relationships to each other. Basic convictions such as these form our everyday picture of the world: the manifest image.
The scientific image, on the other hand, is a system of beliefs that is only based on scientific results. It contains many beliefs that are not contained in the manifest image. At first glance, this may not seem to be a problem. But Mulamustafi? shows convincingly that this is a mistake: The world as it is in itself cannot be both the way the manifest image depicts it and the way the scientific image describes it to be.
Adem Mulamustafic studied and completed his PhD in philosophy at the University of Potsdam. His areas of specialization are metaphysics, philosophy of science, and critical thinking.
Starch is an insoluble polyglucan, comprises of two polymers, namely, the branched α-1,4: α-1,6-D-glucan amylopectin and the almost unbranched α-1,4-D-glucan amylose. The growth of all plants is directly dependent on the accumulation of transitory starch during the daytime when photosynthesis takes place and subsequently starch degradation during the night. Starch phosphorylation takes place by starch-related dikinases called α-glucan, water dikinase (GWD), and phosphoglucan, water dikinase (PWD), and is a very important step in starch degradation. The biochemical mechanisms of phosphorylation of starch are not properly understood. Recent studies have found that there are two starch binding proteins namely, Early Starvation1 (ESV1) and Like Early Starvation1 (LESV), which play an important role in starch metabolism. It has been shown that ESV1 and LESV proteins affect the starch phosphorylation activity of GWD and PWD enzymes, which control the rate of degradation of starch granules. In this thesis, various in vitro assays were performed to identify and understand the mechanism of recombinant proteins; ESV1 and LESV on the starch degradation. The starch degradation was performed by phosphorylation enzymes, GWD and PWD separately. In various enzymatic assays, the influence of the ESV1 and LESV on the actions of GWD and PWD on the surfaces of different native starch granules were analysed. Furthermore, ESV1 and LESV have specifically shown influences on the phosphorylation activities of GWD and PWD on the starch granule surfaces in an antagonistic pattern in such a way that, the GWD mediated phosphorylation were significantly reduced while PWD mediated phosphorylation were significantly increased respectively. In another set of experiments, ISA and BAM hydrolyzing enzymes were used to alter the structure of starch, and then determine the effect of both dikinases mediated phosphorylation in the presence of ESV1 and LESV on the altered starch granules surfaces. In these results, significant decreases in both GWD and PWD mediated phosphorylation were observed in all the treatments containing either ESV1 or LESV proteins only or both ESV1 and LESV. It was also found that LESV preferentially binds to both amylose and amylopectin, while ESV1 binds to highly ordered glucans such as maltodextrins and amylopectin, which are crystalline in structure. Both ESV1 or LESV proteins either individually or in combination have shown influence on the activity of GWD and PWD phosphate incorporation into the starch granules via reduction even though at different percentages depending on the sources of starch, therefore it is difficult to distinguish the specific function between them. The biochemical studies have shown that protein-glucan interaction specifically between ESV1 or LESV or in combination with different species of starch granules has very strong surface binding, or it might be possible that both the proteins not only bind to the surface of the starch granules but also have entered deep inside the glucan structure of the starch granules. However, the results also revealed that ESV1 and LESV did not alter the autophosphorylation of the dikinases. Also, the chain length distribution pattern of the released glucan chains after treatment of starch with ISA enzyme was evaluated with respect to the degree of polymerization (DP) of the different starch granules. Capillary electrophoresis was employed to study the effect of LESV and ESV1 on the chain length distribution. In summary, this study confirms that ESV1 and LESV play an important role in organizing and regulating the starch metabolism process. In the later half, studies were performed to monitor whether the metabolism of carbohydrates and partitioning, contribute to the higher salt tolerance of the facultative halophyte Hordeum marinum when compared to glycophyte Hordeum vulgare. Seedlings with the same size from both species were hydroponically grown at 0, 150, and 300 mM of NaCl for 3 weeks. H. marinum maintained a high relative growth rate, which was found concomitant in higher aptitude plants to maintain efficient shoot tissue hydration and integrity of membrane under salt conditions when compared to H. vulgare. Hence, our data suggested that the change in the starch storage, distribution of soluble sugar concentrations between source and sink organs, and also changes in the level of enzymes involved in the starch metabolism was significant to give insights into the importance of carbohydrate metabolism in barley species with regards to the salt tolerance. Although these results are still in their nascent state, it could be vital for other researchers to formulate future studies. The preliminary results which were studies about the carbohydrate metabolism and partitioning in salt responses in the halophyte H. marinum and the glycophyte H. vulgare revealed that salt tolerance in barley species is not due to osmotic adjustments, but due to other reasons that were not explored in the past studies. However, the activity of DPE2 in H. vulgare was not hampered by the presence of NaCl as observed. While Pho1 and Pho2, activities were highly increased in cultivated barley. These findings could be suggestive of a possible role of these enzymes in the responses of carbohydrate metabolism to salinity. When sea and cultivated barley species were compared, it was discovered that the former had more versatility in carbohydrate metabolism and distribution.
Postcolonial surveillance
(2022)
Postcolonial Surveillance investigates the long history of the European border regime, focusing on the colonial forerunners of today’s border technologies. The book takes a longue durée perspective to uncover how Europe’s colonial history continues to shape the high-tech political present and has morphed into EU border migration policies, border security, and surveillance apparatuses. It exposes the racial hierarchies and power relations that form these systems and highlights key moments when the past and present interact and collide, such as in panoptic surveillance, biopolitical registers, biometric sorting, and deterrent media infrastructure. The technological genealogies assembled in this book reveal the unacknowledged histories that had to be rejected for the seemingly clean, unbiased, and neutral technologies to emerge as such.
The knowledge of transformation pathways and transformation products of veterinary drugs is important for health, food and environmental matters. Residues, consisting of original veterinary drug and transformation products, are found in food products of animal origin as well as the environment (e.g., soil or surface water). Several transformation processes can alter the original veterinary drug, ranging from biotransformation in living organism to environmental degradation processes like photolysis, hydrolysis, or microbial processes. In this thesis, four veterinary drugs were investigated, three ionophore antibiotics Monensin, Salinomycin and Lasalocid and the macrocyclic lactone Moxidectin. Ionophore antibiotics are mainly used to cure and prevent coccidiosis in poultry especially prophylactic in broiler farming. Moxidectin is an antiparasitic drug that is used for the treatment of internal and external parasites in food-producing and companion animals. The main objective of this work is to employ different laboratory approaches to generate and identify transformation products. The identification was conducted using high-resolution mass spectrometry (HRMS). A major focus was placed on the application of electrochemistry for simulation of transformation processes. The electrochemical reactor – equipped with a three-electrode flow-through cell – enabled the oxidation or reduction by applying a potential. The transformation products derived were analyzed by online coupling of the electrochemical reactor and a HRMS and offline by liquid chromatography (LC) combined with HRMS. The main modification reaction of the identified transformation products differed for each investigated veterinary drug. Monensin showed decarboxylation and demethylation as the main modification reactions, for Salinomycin mostly decarbonylation occurred and for Lasalocid methylation was prevalent. For Moxidectin, I observed an oxidation (hydroxylation) reaction and adduct formation with solvent. In general, for Salinomycin and Lasalocid, more transient transformation products (online measurement) than stable transformation products (offline measurements) were detected. By contrast, the number of transformation products using online and offline measurements were identical for Monensin and Moxidectin. As a complementary approach, metabolism tests with rat or human liver microsomes were conducted for the ionophore antibiotics. Monensin was investigated by using rat liver microsomes and the transformation products identified were based on decarboxylation and demethylation. Salinomycin and Lasalocid were converted by human and rat liver microsomes. For both substances, more transformation products were found by using human liver microsomes. The transformation products of the rat liver microsome conversion were redundant, and the transformation products were also found at the human liver microsome assay. Oxidation (hydroxylation) was found to be the main modification reaction for both. In addition, a frequent ion exchange between sodium and potassium was identified. The final two experiments were performed for one substance each, whereby the hydrolysis of Monensin and the photolysis of Moxidectin was investigated. The transformation products of the pH-dependent hydrolysis were based on ring-opening and dehydration. Moxidectin formed several transformation products by irradiation with UV-C light and the main modification reactions were isomeric changes, (de-)hydration and changes of the methoxime moiety. In summary, transformation products of the four investigated veterinary drugs were generated by the different laboratory approaches. Most of the transformation products were identified for the first time. The resulting findings provide an improved understanding of clarifying the transformation behavior.
Die Arbeit untersucht bewaffnete Konfliktszenarien, in denen an multinationalen Militäroperationen beteiligte Staaten während einer Gewahrsamsoperation gegnerische Kräfte oder andere Personen in Gewahrsam nehmen und diese dann an die Kräfte eines anderen Staates, oftmals der Hostnation mit zweifelhafter Menschenrechtsreputation, überstellen. Gewahrsamspersonen laufen dann Gefahr, Opfer erheblicher Rechtsverletzungen zu werden
Does youth matter?
(2022)
This dissertation is a compilation of publications and submitted publication manuscripts that seek to improve the understanding of modern partnership trajectories. Romantic relationships constitute one of the most important dimensions in a person’s life. They serve to satisfy social and emotional needs (Arránz Becker, 2008) and have an impact on various other dimensions of life. Since the 1970s, partnership formation has been characterized by increased heterogeneity, has become less ordered and much more diverse in terms of living arrangements and the number of unions across the life course (Helske et al, 2015; Ross et al, 2009). This dissertation argues that while partnerships have become more unstable, the need for attachment and the importance of relationship have remained high, if not increased, as evidenced by the prevalence of couple relationships that have remained quite stable (Eckhardt, 2015). The life course perspective (Elder, 1994; Elder et al., 2004; Mayer, 2009) offers an appropriate framework for the understanding of partnership formations throughout the life course. This perspective stresses the path dependency of the life course as well as the interdependencies of life domains (Bernardi et al., 2019). Thus, it can be argued that conditions, resources, and experiences in youth have a substantial influence on later life course outcomes. Given the increasing heterogeneity of partnership trajectories, research to understand partnership processes cannot be based only on single events (e.g., marriage or divorce) or life stages, but must be explored in a dynamic context and over a longer period of time. In sum, this thesis argues that partnership trajectories have to be considered from a holistic perspective. Not only single transitions or events are useful to describe modern partnership histories adequately, but rather the whole process. Additionally, as partnership trajectories are linked to various outcomes (e.g., economics, health, effects on children), it is therefore highly relevant to improve our understanding of partnership dynamics and their determinants and consequences. Findings in this field of research contribute to a better understanding of how childhood and youth are of prospective importance for the later partnership trajectories and whether there are any long-term effects of the conditions and resources formed and stabilized in youth, which then help to understand and explain partnership dynamics. Thus, the interest of this thesis lies in the longitudinal description and prediction of the dynamics of partnership trajectories in light of the individual resources formed and stabilized in youth, as well as in the investigation of the consequences of different partnership trajectory patterns on individual well-being. For these objectives, a high demand on the data is required, as prospective data at the beginning of the partnership biography are needed, as well as data on current life dimensions and the detailed partnership history. The German LifE Study provides this particular data structure as it examines life courses of more than 1,300 individuals from adolescence to middle adulthood. With regard to the overall aim of this dissertation, the main conclusion is that early life conditions, experiences, and resources influence the dynamics of individual partnership trajectories. The results illustrate that youth matters and that characteristics and resources anchored in youth influence the timing of early status passages, which sets individuals on specific life paths. However, in addition to personal and social resources, partnership trajectories were also significantly influenced by individuals’ sociodemographic placement. Additionally, individual resources are also linked to the overall turbulence or stability of partnership trajectories. This overall dynamic, which is reflected in different partnership patterns, influences individual well-being, with stability being associated with greater satisfaction, and instability (women), or permanent singlehood (men), having a negative impact on well-being. My analyses contribute to life course research by examining path dependency against the background of various individual factors (socio-structural and psychological characteristics) to model decision-making processes in partnerships in more detail. They do so by including also non-cohabitational union types in the analyses, by accounting for pre-trajectory life conditions and resources, and, most importantly, by modeling the partnership trajectory in a holistic and dynamic perspective, applying this perspective to appropriate and modern statistical methods on a unique dataset.
Characterization of the role of stress - responsive NAC transcription factors ANAC055 and ATAF1
(2022)
Natural hazards pose a threat to human health and life. In Germany, where the research for this thesis was conducted, numerous weather extremes occurred in the recent past that caused high numbers of fatalities and huge financial losses. The focus of this research is centred around two relevant natural hazards: heat stress and flooding. Preventing negative health impacts and deaths, as well as structural and monetary damage is the purpose of risk management and this requires citizens to adapt as well. Risk communication is implemented to foster people’s risk perception and motivate individual adaptation. However, methods of risk and crisis communication are often not evaluated in a structured manner. Much interdisciplinary research exists on both risk perception and adaptation, however, not much is known on the connection between the two. Furthermore, the existing research on risk communication is often not theory-driven and its impact on individual adaptation and risk perception is not thoroughly documented. This dissertation follows three research aims: (1) Compare psychological theories that contribute to natural hazard research. (2) Explore risk perception and adaptive behaviour by applying multiple methods. And (3) evaluate one risk communication method and one crisis communication method in a theory-driven manner to determine their impact on risk perception and adaptive behaviour. First, a literature review is provided on existing psychological theories which aim to explain the behaviour of individuals with regards to natural hazards. The three key theories included are the Protection Motivation Theory (PMT), the Protective Action Decision Model (PADM), and the Risk Information Seeking and Processing Model (RISP). Each of these are described and compared to each other with a focus on their explanatory power and practical significance in interdisciplinary research. Theoretical adaptations and possible extensions for future research are proposed for the presented approaches. Second, a multimethod field study on heat stress at an open-air event is presented. Face-to-face surveys (n = 306) and behavioural observations (n = 2750) were carried out at a horticultural show in Würzburg in summer 2018. The visitors’ risk perception, adaptive behaviour, and activity level were analysed and compared between hot days, summer days, and rainy days, applying correlation analyses, ANOVA, and multiple regression analyses. Heat risk perception was generally high, but most respondents were unaware of heat warnings on the day of their visit. During hot days the highest level of adaptation and lower activity levels were observed. Discrepancies between reported and observed adaptation emerged for different age groups.. Third, a telephone and web-based household survey on heat stress was conducted in the cities of Würzburg, Potsdam, and Remscheid in 2019 (n = 1417). The PADM served as the study’s theoretical framework. In multiple regression analyses the PADM factors of environmental and demographic context, risk communication, and psychological processes explained a substantial share of variance of protection motivation, protective response, and emotion-focused coping. Elements of crisis communication of a heat warning were evaluated experimentally. Results showed that understanding and adaptation intention was significantly higher in individuals that had received action recommendations alongside the heat warning. Fourth, the focus is set on a risk communication method of the flood context. A series of workshops on individual flood protection was carried out in six different settings. The participants (n = 115) answered a pretest-posttest questionnaire. Mixed-model analyses revealed significant increases in self-efficacy, subjective knowledge, and protection motivation. Stronger effects were observed in younger participants and those with lower levels of previous knowledge on flood adaptation as well as no flood experience. The findings of this thesis help to understand individual adaptation, as well as possible impacts of risk and crisis communication on risk perception and adaptation. The scientific background of this work is rooted in the disciplines of psychology and geosciences. The two theories PMT and PADM proved to be useful theoretical frameworks for the presented studies to suggest improvements in risk communication methods. A broad picture of individual adaptation is captured through a variety of methods of self-reports (face-to-face, telephone-based, web-based, and paper-pencil surveys) and behavioural observations, which recorded past and intended behaviour. Alongside with further methodological recommendations, the theory-driven evaluations of risk and crisis communication methods can serve as best-practice examples for future evaluation studies in natural hazard research but also other sciences dealing with risk behaviour to identify and improve effective risk communication pathways.
Social networking site use and well-being - a nuanced understanding of a complex relationship
(2022)
Social Networking Sites (SNSs) are ubiquitous and attract an enormous chair of the digital population. Their functionalities allow users to connect and interact with others and weave complex social networks in which social information is continuously disseminated between users. Besides the social value SNSs are generating, they likewise attract companies and allow for new forms of marketing, thereby creating considerable economic value alike. However, as SNSs grew in popularity, so did concerns about the impact of their use on social interactions in general and the well-being of individual users in particular. While existing scientific evidence points to both risk as well as benefits of SNS use, research still lacks a profound understanding of which aspects of SNSs enable an impact on well-being and which psychological processes on the part of the users underly and explain this relationship. Therefore, this thesis is dedicated to an in-depth exploration of the relationship between SNS use and well-being and aims to answer how SNS use can impact well-being. Primarily, it focuses on the unique technological features that characterize SNSs and enable potential well- being alterations and on specific psychological processes on the part of the users, underlying and explaining the relationship. For this purpose, the thesis first introduces the concept of well- being. It continues by presenting SNSs’ unique technological features, divided into specifics of the content disseminated on SNSs and the network structure of SNSs. Further, the thesis introduces three classes of psychological processes assumed most relevant for the relationship between SNSs and well-being: other-focused, self-focused, and contrastive processes.. It is assumed that the course and quality of these common processes change in the SNS context and that a complex interplay between the unique features of SNSs and these processes determines how SNSs may ultimately affect users' well-being - both in positive and negative ways. The dissertation comprises seven research articles, each of which focusses on a particular set of SNS characteristics, their interplay with one or more of the proposed psychological processes, and ultimately the resulting effects on user well-being or its key resilience and risk factors. The seven articles investigate this relationship using different methodological approaches. Three articles are based on either systematic or narrative literature reviews, one applies an empirical cross-sectional research design, and three articles present an experimental investigation. Thematically, two articles revolve around SNS use’s effect on self-esteem. Three articles examine the specific role of the emotion of envy and its potential to establish and perpetuate a well-being-damaging social climate on SNSs. The two last articles of this thesis revolve around the established assumption that active and passive SNS use, as different modalities of SNS use, cause differential effects on users’ well-being due to the involvement of different psychological processes. The results of this thesis illustrate different ways how SNSs can affect users’ well-being. The results suggest that especially contrastive processes play a decisive role in explaining potential well-being risks for SNS users. Their interplay with certain SNS features seems to foster upward social comparisons and feelings of envy, potentially leading to a complex set of deleterious effects on users’ well-being. At the same time, the findings illuminate ways in which SNSs can benefit users and their self-esteem – especially when SNS use promotes self- focused and social-feedback-based other-focused processes. The thesis and their findings illustrate that the relationship between SNSs and well-being is complex. Therefore, a nuanced perspective, taking into consideration both the technological uniqueness of SNSs and the psychological processes they are enabling, is crucial to understand how these technologies affect their users in good and potentially harmful ways. On the one hand, the gathered insights contribute to research, providing novel insights into the complex relationship between SNS use and well-being. On the other hand, the results enable a focused and action-oriented derivation of recommendations for stakeholders such as individual users, policymakers, and platform providers. The findings of this thesis can help them to better combat SNS-related risks and ultimately ensure a healthy and sustainable environment for users - and thus also the economic values of SNSs - in the long term.
Pannexin 1
(2022)
Hypoxic pulmonary vasoconstriction is an active alveolar hypoxia-caused physiological response redirecting pulmonary blood flow from poorly ventilated areas to better oxygenated lung regions in order to optimize oxygen supply. However, the signaling pathways underlying this pulmonary vascular response remain an area under investigation. In the present study I investigated the functional relevance of Pannexin 1 (Panx1)-mediated ATP release in hypoxic pulmonary vasoconstriction and chronic hypoxic pulmonary hypertension using murine isolated perfused lungs, chronic hypoxic mice, and pulmonary artery smooth muscle cell culture. In isolated mouse lungs, switch to hypoxic gas induced a marked increase in pulmonary artery pressure. Pharmacological inhibition of Panx1 using probenecid, Panx1 specific inhibitory peptide (10Panx1) or spironolactone as well as genetic deletion of Panx1 in smooth muscle cells diminished hypoxic pulmonary vasoconstriction in isolated perfused mouse lungs. Fura-2 imaging revealed a reduced Ca2+ response to hypoxia in pulmonary artery smooth muscle cells treated with spironolactone or 10Panx1. Although these findings suggested an important role of Panx1 in HPV, neither smooth muscle cell nor endothelial cell specific genetic deletion of Panx1 prevented the development of pulmonary hypertension in chronic hypoxic mice. Surprisingly, hypoxia did not induce ATP release and inhibition of purinergic receptors or ATP degradation by ATPase failed to decrease the pulmonary vasoconstriction response to hypoxia in isolated perfused mouse lungs. However, Panx1 antagonism as well as TRPV4 inhibition prevented the hypoxia-induced increase in intracellular Ca2+ concentration in pulmonary artery smooth muscle cells in an additive manner suggesting that Panx1 might modulate intracellular Ca2+ signaling independently of the ATP-P2-TRPV4 signaling axis. In line with this assumption, overexpression of Panx1 in HeLa cells increased intracellular Ca2+ concentrations in response to acute hypoxia. Conclusion: In this study I identifiy Panx1 as novel regulator of HPV.. Yet, the role of Panx1 was not attributable to the release of ATP and downstream P2 signaling pathways or activation of TRPV4 but rathter relates to a role of Panx1 as indirect or direct modulator of the Ca2+ response to hypoxia in PASMCs. Genetic deletion of Panx1 did not influence the development of chronic hypoxic pulmonary hypertension in mice.
East and South
(2022)
"What is 'Europe' in academic discourse? While Europe tends to be used as shorthand, often interchangeable with the 'West', neither the 'West' nor 'Europe' are homogeneous spaces. Though postcolonial studies have long been debunking Eurocentrism in its multiple guises, there is still work to do in fully comprehending how its imaginations and discursive legacies conceive the figure of Europe, as not all who live on European soil are understood as equally 'European'. This volume explores this immediate need to rethink the axis of postcolonial cultural productions, to disarticulate Eurocentrism, to recognise Europe as a more diverse, plural and fluid space, to draw forward cultural exchanges and dialogues within the Global South. Through analyses of literary texts from East-Central Europe and beyond, this volume sheds light on alternative literary cartographies - the multiplicity of Europes and being European which exist both as they are viewed from the different geographies of the global South, and within the continent itself. Covering a wide spatial and temporal terrain in postcolonial and European cultural productions, this volume will be of great interest to scholars and researchers of literature and literary criticism, cultural studies, post-colonial studies, Global South studies and European studies"
Seismology, like many scientific fields, e.g., music information retrieval and speech signal pro- cessing, is experiencing exponential growth in the amount of data acquired by modern seismo- logical networks. In this thesis, I take advantage of the opportunities offered by "big data" and by the methods developed in the areas of music information retrieval and machine learning to predict better the ground motion generated by earthquakes and to study the properties of the surface layers of the Earth. In order to better predict seismic ground motions, I propose two approaches based on unsupervised deep learning methods, an autoencoder network and Generative Adversarial Networks. The autoencoder technique explores a massive amount of ground motion data, evaluates the required parameters, and generates synthetic ground motion data in the Fourier amplitude spectra (FAS) domain. This method is tested on two synthetic datasets and one real dataset. The application on the real dataset shows that the substantial information contained within the FAS data can be encoded to a four to the five-dimensional manifold. Consequently, only a few independent parameters are required for efficient ground motion prediction. I also propose a method based on Conditional Generative Adversarial Networks (CGAN) for simulating ground motion records in the time-frequency and time domains. CGAN generates the time-frequency domains based on the parameters: magnitude, distance, and shear wave velocities to 30 m depth (VS30). After generating the amplitude of the time-frequency domains using the CGAN model, instead of classical conventional methods that assume the amplitude spectra with a random phase spectrum, the phase of the time-frequency domains is recovered by minimizing the observed and reconstructed spectrograms. In the second part of this dissertation, I propose two methods for the monitoring and characterization of near-surface materials and site effect analyses. I implement an autocorrelation function and an interferometry method to monitor the velocity changes of near-surface materials resulting from the Kumamoto earthquake sequence (Japan, 2016). The observed seismic velocity changes during the strong shaking are due to the non-linear response of the near-surface materials. The results show that the velocity changes lasted for about two months after the Kumamoto mainshock. Furthermore, I used the velocity changes to evaluate the in-situ strain-stress relationship. I also propose a method for assessing the site proxy "VS30" using non-invasive analysis. In the proposed method, a dispersion curve of surface waves is inverted to estimate the shear wave velocity of the subsurface. This method is based on the Dix-like linear operators, which relate the shear wave velocity to the phase velocity. The proposed method is fast, efficient, and stable. All of the methods presented in this work can be used for processing "big data" in seismology and for the analysis of weak and strong ground motion data, to predict ground shaking, and to analyze site responses by considering potential time dependencies and nonlinearities.
We live in an aging society. The change in demographic structures poses a number of challenges, including an increase in age-associated diseases. Delirium, dementia, and depression are considered to be of particular interest in the field of aging and mental health. A common theory regarding healthy aging and mental health is that the highest satisfaction and best performance is achieved when a person's abilities match the demands of their environment. In this context, the person's environment includes both the physical and the social environment. Based on this assumption, this dissertation focuses on the investigation of non-pharmacological interventions that modify environmental factors in order to facilitate the prevention and treatment of mental disorders in older patients and their caregivers. The first part of this dissertation consists of two publications and deals with the prevention of postoperative delirium in elderly patients. The PAWEL study investigated the use of a multimodal, non-pharmacological intervention in the routine care of patients aged 70 years or older undergoing elective surgery. The intervention included an interdepartmental delirium prevention team, daily use of seven manualized “best practice” procedures, structured staff training on delirium, and the adaptation of the hospital environment to the patients’ needs. The second part of the dissertation used a meta-analysis to investigate whether technology-based interventions are a suitable form of support for informal caregivers of people with dementia. Subgroup analyses were conducted to examine the effect of different types of technology on caregiver burden and depressive symptoms. The following main results were found: The PAWEL study showed that the use of a multimodal, non-pharmacological intervention resulted in a significantly lower incidence rate of postoperative delirium and reduced days with delirium in the intervention group compared to the control group. However, this difference could not be observed in the group of patients undergoing elective cardiac surgery. The results of the meta-analysis showed that technology-based interventions offer a promising alternative to traditional “face-to-face” services. Significant effect sizes could be found in relation to both the burden and the depressive symptoms of caregiving relatives. These results provide further important information on the significant impact of non-pharmacological interventions that modify environmental factors on mental health, and support the consideration of such interventions in the prevention and treatment of mental disorders in both older patients and their caregivers.