This dissertation examines the construction and instrumentalisation of Generation Y as a discourse in the US and its translation to Turkey. It is guided by the inquiry to understand the enduring emphasis and popularity of generational thinking, despite the lack of empirical evidence and its theoretical shortcomings.
The analysis examines, in sequential order, influential actors shaping the Gen Y discourse in the US, uncovering implicit and explicit claims associated with it. The focus then shifts to Turkey, where the discourse gained prominence during the Gezi Park Protests, exploring local influencers and delving into the evolution and translation of Generation Y discourse within this unique context. The investigation extends to companies in Turkey, examining how employees and companies relate to and instrumentalise the Gen Y discourse in their management practices.
To address these inquiries, the dissertation adopts a constructivist approach, combining thematic analysis of texts on Gen Y from mainstream newspapers, popular business magazines, consultancy reports, and bestselling books in Turkish and English, with the in-depth interviews conducted with white-collar workers in Turkey.
The dissertation highlights the role of management and consultancy practitioners in constructing and disseminating the Generation Y discourse, suggesting that they employ strategies similar to those used for popular management fads and fashions, including the use of an ambiguous and polysemous language. The analysis reveals that, despite theoretical controversies, Generation Y is portrayed as a scientific concept based on birth cohorts while simultaneously drawing strategically on historical connotations of generational identity, aligning itself with alternative understandings of generations (such as kinship structures and youth as a driving force in shaping history). This research suggests that the Gen Y discourse is deeply embedded in the idea of a “new” era marked by digitalisation and widespread internet use. In this context, "generational conflicts" and "becoming outdated" are presented as a single problem, forming a central message within the discourse. Consequently, Gen Y discourse extends beyond addressing generational conflicts or explaining youth movements; it is presented as a panacea offering solutions to all current and foreseeable future problems.
View lessThe development of metal-nitrogen-carbons (M-N-Cs) has gained significant momentum in the 21st century, driven by their potential as sustainable alternatives to precious metals for electrocatalytic applications. However, as the pyrolytic synthesis often produces highly disordered carbonized materials, it can be challenging to accurately characterize the active sites and their involvement in the catalytic reactions. In this regard, quantum chemical methodologies like density functional theory (DFT) could provide crucial atomic-level information to guide the characterization and optimization of M-N-Cs. In this thesis, I present computational studies related to the synthesis of M-N-Cs in the first part, followed by their electrocatalytic applications in the second part. In parallel to these studies, potential factors for the material degradation during the synthesis and applications are also identified, especially for the generally active but unstable Fe-N-Cs.
Inspired by the recent success of the templating-transmetallation strategy in producing M-N-Cs with dense active sites, the first part of the thesis features a computational investigation on the chemical properties of metals at the MN4 sites. By constructing and optimizing structural models for the incorporation of MN4 motifs in conductive carbon matrices, we determined several advantages of using molecular DFT methods for modeling the active sites, especially the structurally complex pyrrolic MN4 motifs. Using these models, we further examined the trends among the first-row transition metals pertaining their binding within the MN4 site as well as their relative affinity to the pyrrolic or pyridinic motifs. It could be shown that metals with more significant ionic binding character, such as Zn and Mg, are more likely to form the pyrrolic MN4 sites than the catalytically active metals like Fe and Co, leading to the successful characterization of the pyrrolic MN4 sites from synthesis strategies which utilized Zn2+ or Mg2+ as the sacrificial templating ions. In addition, the binding of Zn was determined to be the weakest among the transition metals, making it an optimal choice for the subsequent transmetallation.
As the transmetallation step generally retains the original structure of the active site, in addition to its morphological properties and active site densities, it became a crucial starting point for intrinsic activity comparisons among metals in the M-N-Cs. In the second part of this thesis, the electrocatalytic mechanisms for the oxygen reduction reaction (ORR) and the carbon dioxide reduction reaction (CO2RR) on the previously identified pyrrolic MN4 sites are presented along with corresponding side reactions including the Fenton reaction and the hydrogen evolution reaction (HER). The combined efforts of theory and experiment led to the identification of inconspicuous species at the interface, such as hydroxides for alkaline ORR, water for the Fenton reaction, and cations for the CO2RR, which in fact play an active role in the mechanisms of the respective reactions. For the ORR, we determined the involvement of the outer-sphere electron transfer in the reaction mechanism, especially in the alkaline medium, leading to the formation of H2O2 whose subsequent reactions could depend on specific interactions with the MN4 site. For the CO2RR, a theory-experiment contradiction in the activity and selectivity of Ni-N-Cs could be resolved with the inclusion of alkali metal ions in the mechanism, whose adsorption was made favorable by the pyrrolic N atoms at the MN4 site. Overall, these insights derived with DFT provide strong theoretical support for the knowledge-based optimization of the activity, selectivity and stability of M-N-Cs for sustainable energy conversion applications.
View lessDuring lactation, the gut mucosa undergoes expansion to accommodate increased food consumption and absorption, in order to meet the increased energy demands associated with nurturing neonates. Previous studies have investigated the impact of litter size, hormones, and diet on lactation-induced gut hyperplasia, yet the role of immune cells remained unexplored. The recently discovered innate lymphocytes type 3 (ILC3s) have emerged as key players not only in organizing lymphoid tissues but also in protecting the intestinal epithelium against tissue damage and genotoxic stress. Thus, we explored the contribution of ILC3s to lactation-induced gut hyperplasia. Our immunofluorescence analysis revealed that mice lacking RORγt, the transcription factor crucial for ILC3 development and function, exhibited shorter villi and reduced proliferation in the crypts, where the intestinal stem cells reside. Subsequent analysis using IL-22-deficient mice, a cytokine primarily expressed by ILC3s, suggests that ILC3s promote lactation-induced gut hyperplasia in an IL-22-dependent manner. Furthermore, our findings demonstrated that STAT3 in the intestinal epithelium, known to be stimulated by IL-22 and EGF, also contributes to increased proliferation and villus growth in lactating mice.
Flow cytometry experiments and histological analyses confirmed increased ILC3 proliferation during lactation and enlargement of the clusters ILC3s form proximal to the crypts, namely cryptopatches and isolated lymphoid follicles. Bulk RNA sequencing and leukocyte stimulation experiments between non-pregnant (NP) and lactating mice, confirmed the upregulation of IL-22 in ILC3s during lactation, a finding further validated through the analysis of IL-22 tdTomato reporter mice. Single-cell RNA sequencing of intestinal epithelial cells from both ILC3-sufficient and deficient mice unveiled downregulation of the EGF signaling in the gut, which was validated by quantification of EGFR phosphorylation in epithelial cells. The phosphorylation of EGFR, linked to ligand binding, was confirmed to be associated with EGF upregulation during lactation, originating from mesenchymal PDPN+ cells. Notably, RORγt-dependent cells were found to regulate EGF production in mesenchymal cells in an IL-22-dependent manner upon lactation.
Moreover, our study demonstrated that IL-22 modulates genes associated with nutrient absorption in gut epithelium in vitro, differentially to the IL-20 and IL-24 cytokines, which also bind to the IL-10RB receptor. Lastly, we observed that lactating RORγt and IL22-deficient mice consumed more food than the WT control mice, presumably to compensate for reduced food absorption. However, due to their reduced absorptive epithelial surface, the body weight of IL-22-sufficient offspring nurtured from ILC3- and IL-22-deficient mice was reduced.
View lessOpioid receptor ligands (opioids) represent the gold standard for severe pain treatment. However, approved opioids possess many serious side effects even if they are used according to medical instructions. As a result, opioid use leads to thousands of hospitalizations and deaths each year. Four different opioid receptor subtypes exist but approved opioids mainly activate the μ-opioid receptor (MOR). Activation of the κ-opioid receptor (KOR) emerged as a promising strategy to sufficiently alleviate pain while improving the side effect profile of opioids. However, KOR-related side effects and the high structural similarity of the opioid receptor subtypes renders rational drug design challenging. The opioid receptor system is not only involved in pain modulation, but also in the maintenance of mood homeostasis. Antagonism of the KOR recently emerged as a promising strategy for the development of novel antidepressants with fast-onset antidepressant effects that are also effective against suicidal intent. However, the chemical space of KOR selective antagonists is limited. No short-acting and selective KOR antagonists have been approved so far. This dissertation encompasses retrospective and prospective studies that focus on in silico techniques to address current questions in opioid research. The first three articles, conducted retrospective in silico analyses of HS-731, an opioid agonist, Compound A, a KOR/MOR dual antagonist, and Salvinorin A (SalA), a non-basic, KOR-selective agonist. These analyses aimed to improve our limited understanding of the factors that determine opioid receptor activity and selectivity. The investigated compounds are of high pharmacological interest. HS-731 represents an analgesic with a potentially improved safety profile due to its exclusion from the central nervous system (CNS). Compound A has a unique scaffold that may overcome the unfavorable kinetic profile of current antidepressant opioids. SalA represents a non-basic agonist with exceptional KOR selectivity that potentially binds dissimilar to basic opioids at the KOR. Protein-ligand binding modes of the compounds at the opioid receptor subtypes were predicted and selectivity determinants rationalized. Important protein-ligand interactions responsible for the opioid receptor activity of these ligands were highlighted. A new binding site for SalA above the typical morphinan binding site that is highly non-conserved was discovered. The SalA binding mode is consistent with structure-activity relationship (SAR) data and rationalizes the exceptional receptor subtype selectivity of SalA at the KOR. In addition, a partial agonism-inducing mechanism for the KOR was hypothesized involving an interaction between the extracellular oriented parts of the transmembrane helices 5 and 6. Typical opioids possess a basic amine moiety interacting with a conserved aspartate residue inside the binding site. Since the discover of non-basic and highly KOR-selective SalA, the design of non-basic opioids became a new and promising strategy for the selective activation of the KOR, circumventing MOR-associated severe side effects. However, the number of known non-basic opioids is strongly limited and rational drug design of new non-basic opioids is the hindered by the lack of understanding about the binding mode of SalA. In the fourth article included in this dissertation, a prospective 3D pharmacophore-based virtual screening campaign was conducted. The campaign was based on the SalA binding mode postulated in the third article. The aim was to determine new non-basic and selective KOR ligands. Pharmacological in vitro experiments confirmed two of the suggested compounds to activate the KOR with nanomolar potency and good subtype selectivity. One hit compound possesses a full agonistic and one compound shows a partial agonistic profile at the KOR. Both hit compounds share a novel spiro-moiety-containing scaffold. Overall, the findings of this dissertation provide new mechanistic insights into opioid receptor activation in the context of current progress in structural biology, and lay the basis for improved, rational drug design of safer analgesics and novel antidepressants with KOR activity.
View lessZiel dieser Studie war es, die viruzide Wirksamkeit von alternativen Desinfektionsverfahren für Oberflächen, ohne den Einsatz von Feucht- und Wischdesinfektion, zu ermitteln. Dabei wurde die Anwendung der Trockenvernebelung aerosolisierter Peroxyessigsäure (aPES), UV C-LED-Strahlung bei 233 und 270 nm sowie einer UV C-Quecksilberlampe bei 254 nm und Kaltplasmastrahlung untersucht. Für diesen Zweck wurden unbelebte Oberflächen wie Edelstahl, Glas und PVC gegenüber einem breiten Erregerspektrum aus behüllten und unbehüllten Viren getestet. Die Auswahl geeigneter Viren erfolgte einerseits anhand der DVV-RKI-Leitlinien, der DVG-Leitlinien und der DIN EN 17272:2020. Andererseits wurden gezielt noch weitere Viren (MS 2 Bakteriophage, Bovines Coronavirus) ausgewählt und hinsichtlich ihrer Eignung als Surrogate untersucht. Zur jeweiligen Anwendung der einzelnen Methoden wurden entsprechende Keimträger aus den unterschiedlichen Materialien eingesetzt, auf denen die virushaltigen Suspensionen angetrocknet wurden. Die anschließende Quantifizierung des Desinfektionserfolges erfolgte durch Abspülen der Keimträger und nachfolgender Titration auf empfänglichen Zellkulturen. Da sowohl der UV C-LED-Strahler mit einer Wellenlänge von 233 nm als auch der Kaltplasmastrahler primär für die Desinfektion von belebten Oberflächen vorgesehen sind, wurde deren zytotoxisches Potenzial sowie die antivirale Wirksamkeit auch auf 2D-Monolayerkulturen und einem etablierten 3D-Schleimhautmodell getestet.
View lessDie Gebärparese ist eine der wichtigsten Stoffwechselerkrankungen im peripartalen Zeitraum bei Holstein Friesian Kühen. Ursächlich dafür ist eine zu niedrige Kalziumkonzentration im Blut. Bei dem Auftreten von Milchfieber scheint die Serumphosphatkonzentration ebenfalls eine wichtige Rolle zu spielen.
In der vorliegenden Untersuchung wurden von 291 Kühen nach der Kalbung Blutproben über einen Zeitraum von 24 Stunden entnommen und die Werte von Kalzium und anorganischem Phosphat im Serum erfasst. Mit Hilfe der dokumentierten Daten soll der Verlauf von Phosphat post partum im Blutserum im Tagesprofil dargestellt werden und herausgestellt werden, welchen Einfluss kuhassoziierte und managementassoziierte Faktoren auf die Phosphatkonzentration im Serum haben.
Die Untersuchung wurde auf einem Milchviehbetrieb in Mecklenburg-Vorpommern mit 2260 Kühen im Zeitraum von Juli 2014 bis März 2015 durchgeführt. Dazu wurden von den Tieren ab der 1. Laktation Blutproben im zeitlichen Abstand von 2 Stunden entnommen. Die Tiere wurden je nach Fragestellung in unterschiedliche Gruppen randomisiert eingeteilt und haben innerhalb der Gruppen in einem ähnlichen Zeitraum gekalbt.
Es wird festgestellt, dass die Laktationszahl einen wesentlichen Einfluss auf die Serumphosphatkonzentration hat. Tiere ab der 3. Laktation zeigen signifikant niedrigere Werte. In der vorliegenden Untersuchung haben einige Tiere ab der 2. Laktation einen Kalziumbolus erhalten. Diese Behandlungsmethode scheint jedoch keinen Einfluss auf die Konzentration von Phosphat zu haben. Auch die Gabe eines Phosphor-Bolus im Vergleich zu einem Kalzium-Bolus zeigt keine signifikanten Unterschiede auf die Phosphatkonzentration. Hingegen zeigen Tiere, die eine Kalzium-Infusion i.v. unmittelbar nach der Kalbung erhalten haben, einen deutlich schnelleren Anstieg der Serumphosphatwerte und somit höhere Werte über einen Verlauf von 24 Stunden. Ebenso haben eine reduzierte Melkhäufigkeit und eine reduzierte Menge des ermolkenen Kolostrums einen signifikanten Einfluss auf die Serumphosphatwerte. Weiteren Tieren wurde p.p. ein Kalbetrunk verabreicht. Diese Behandlungsmethode weist keinen signifikanten Einfluss auf die Phosphatkonzentration auf.
Ein weiterer signifikanter Einflussfaktor auf die Serumphosphatkonzentration ist die Wahl des Blutgefäßes zur Probenentnahme. In der vorliegenden Arbeit sind die Konzentrationen von Phosphat bei Blutproben aus der V. jugularis deutlich geringer, als bei Proben aus der V./A. coccygea oder der Eutervene. Dies sollte bei der Blutprobenentnahme berücksichtigt werden.
In der Untersuchung wurde deutlich, dass Tiere mit einer Hypophosphatämie zu über 50 % ebenfalls eine Hypokalzämie aufweisen. Somit lässt sich ein Zusammenhang zwischen dem Auftreten einer Gebärparese und der Phosphatkonzentration nachweisen. Aufgrund des signifikanten Einflusses der Kalzium-Infusion auf die Serumphosphatkonzentration lässt dies die Schlussfolgerung zu, dass diese Maßnahme zur Behandlung einer Hypokalzämie ebenso sinnvoll für die Behandlung einer Hypophosphatämie erscheint. Die orale Gabe von Kalzium und Phosphor, beispielsweise in Form eines Bolus, kann hierbei ergänzend erfolgen.
Die untersuchten Tiere zeigen unabhängig von der Behandlung einen ähnlichen Verlauf der Phosphatwerte über einen Zeitraum von 24 Stunden nach der Kalbung. Es stellt sich hier die Frage, ob sich diese Tagesdynamik der Serumphosphatkonzentration unabhängig vom Verlauf der Kalziumkonzentration zeigt. Um dies abschließend zu klären, müsste man die Blutprobenentnahme über einen längeren Zeitraum fortsetzen.
View lessIn der Humanmedizin sowie im Distanzpferdesport wurde bereits festgestellt, dass nach Ausdauerbelastungen Anzeichen eines „Exercise induced cardiac fatigue“ auftreten können. Diese äußern sich in einer reduzierten diastolischen und zum Teil auch systolischen Myokardverformung und auch Myokardgeschwindigkeit. Im Vielseitigkeitssport wurden bisher noch keine Studien mit der Gewebedopplerechokardiographie sowie dem Speckle-Tracking durchgeführt. Ziel dieser Studie war es, letztendlich von 19 Vielseitigkeitspferden die Veränderungen der Funktion des Myokards sonographisch nach einem Geländeritt, nach 24 Stunden sowie im Laufe der Saison zu beurteilen. Die Pferde wurden dafür am Morgen vor dem Geländeritt, 30 Minuten danach sowie 24 Stunden später echokardiographisch untersucht. Alle Pferde wurden zuvor in der Winterpause vor der Saison klinisch und echokardiographisch untersucht und als herzgesund beurteilt. Die Untersuchungen für diese Studie erfolgten mehrmals in der kompletten Turniersaison. Es wurden Pferde in unterschiedlichen Turnierschwereklassen untersucht. Die Belastungseinheiten betrugen zwischen ca. 3.000 – 5.000 m. Das Durchschnittstempo betrug zwischen 400 – 570 m/min. Die Gewebedopplerechokardiographie gilt als ein Verfahren, um die Spitzengeschwindigkeiten des Myokards in der Systole und Diastole zu bestimmen. Die Ergebnisse des PW-Dopplers zeigten eine reduzierte diastolische Funktion des Myokards nach der Belastung. Da diese Messungen durch Vor- und Nachlast beeinflusst werden können, lässt es sich diskutieren, ob es sich hierbei um eine kardiale Ermüdung handelt oder es durch Veränderungen der Vor- und Nachlast nach der Belastung zu einer veränderten Funktion des Myokards gekommen ist. Eine ausreichende Erholung mit Normalisierung der Werte nach 24 Stunden war größtenteils gegeben. Es konnte zudem keine reduzierte systolische Funktionfestgestellt werden. Im Laufe der Untersuchungsmonate sind die Myokardgeschwindigkeiten zum Teil angestiegen. Da diese Veränderungen bereits bei trainierten Athleten nachgewiesen wurden, lässt dies auf einen Trainingseffekt im Laufe der Saison schließen. Mithilfe des 2D-Speckle-Trackings werden die lokalen Myokardfunktionen bzw. die Myokardverformungen beurteilt. Es konnte eine vermehrte kontraktile Funktion und Relaxation des Myokards nach der Belastung festgestellt werden. Die ermittelten Werte für Strain und Strain rate zeigen eine Erhöhung nach der Belastung. Der Vorteil dieses Verfahrens besteht in der Unabhängigkeit bei Volumenveränderungen des Herzens. Im Laufe der Saison hat sich die Strain und Strain rate jedoch reduziert. Diese Reduzierung kann auf den vermehrten Parasympathikus und reduzierten Sympathikus zurückgeführt werden. Dies wiederum kann durch den verbesserten Trainingsstatus der Pferde im Laufe der Saison verursacht sein. Zusammenfassend kann gesagt werden, dass die Ergebnisse dieser Studie für eine verminderte Myokardgeschwindigkeit in der frühen Diastole direkt nach der Belastung sprechen. Eine reduzierte diastolische Funktion nach der Belastung, die mithilfe des PW-Dopplers untersucht wurde, liegt vor, müsste jedoch unter Berücksichtigung von Volumenveränderungen bestätigt werden, bevor von einem eindeutigen „cardiac fatigue“ gesprochen werden kann. Die Erholung am nächsten Morgen war größtenteils gegeben. Im Laufe der Saison lassen die Ergebnisse auf einen positiven Trainingseffekt schließen. Die beiden Ultraschallverfahren, PW-Doppler und Speckle-Tracking, stellen sich zum Thema Leistungsdiagnostik als zwei geeignete Verfahren in der Pferdekardiologie dar.
View lessBiodegradable poly(lactide-co-glycolide) (PLGA) microparticles enable the controlled parenteral administration of drugs. Commonly used microencapsulation methods require the dissolution of PLGA in organic solvents. The removal of these solvents during the manufacturing process is essential to obtain solid microparticles. In addition, a low residual solvent content must be achieved in the final product to ensure storage stability and patient safety. In this dissertation the solvent removal during the preparation of microparticles with the O/W solvent extraction/evaporation method was investigated. In this method, an organic (O) phase containing drug, PLGA and organic solvent (dichloromethane or ethyl acetate) was emulsified in an aqueous polyvinyl alcohol solution (W) by a classical batch process or by microfluidic flow focusing. The effect of various formulation and process parameters was investigated in order to optimize the properties of PLGA microparticles with regard to minimal residual solvent levels at high drug loadings and encapsulation efficiencies and optimal drug release profiles. The initial removal of organic solvent had a great effect on the properties of the microparticles and is usually controlled by two steps, the solvent dissolving in the continuous aqueous phase and the solvent evaporation rate. One-step dilution and continuous diafiltration were investigated to control the initial solvent extraction. The latter replaced the normally required large-volume manufacturing equipment and the O/W emulsion transfer. Accelerated extraction of the PLGA solvent dichloromethane shortened the process time until the microparticles were solidified and thus collectable. Increasing the diafiltration rate increased the particle size, porosity and drug loading of the microparticles. The encapsulation efficiency of risperidone was significantly increased from 62 % to up to 80 % in PLGA 503H microparticles and from 27 % to up to 75 % in PLGA 753S microparticles. A slower and more uniform solidification of the end-capped and higher lactide content PLGA 753S was identified as the reason for the increased drug loss without diafiltration. The residual dichloromethane content was not affected by diafiltration, but decreased by increasing the temperature, because the final solvent removal was limited by the diffusivity within the PLGA phase. Accelerated solvent extraction by diafiltration did not affect the in-vitro release of risperidone from both PLGA 503H and PLGA 753S microparticles. The effect of diafiltration on the extent of dexamethasone burst release depended on the drug loading. Increased porosity enhanced percolation if a large amount of undissolved drug crystals was present in the PLGA matrix. By increasing the process temperature during diafiltration, the unwanted burst release could be reduced because of a reduced microparticle porosity. Due to its complete miscibility with water, methanol as a co-solvent was extracted significantly faster than dichloromethane from the dispersed phase. Increasing the methanol content above 2.5 % (w/w) resulted in an increased porosity, drug loss and burst release. The final dichloromethane extraction was faster, although methanol had already been completely extracted from the PLGA-phase. The residual dichloromethane content after 24 h was reduced from 2.4 % (w/w) (without methanol) to below 0.5 % (w/w) if ≥ 2.5 % (w/w) methanol were used as a co-solvent. The resulting porosity did not explain this, because, if caused by diafiltration, it had no effect on the residual solvent content. Therefore, the effect of alcohols in the continuous phase on the solvent extraction was investigated further. The final removal of the residual solvent from the microparticles was performed by wet extraction and secondary drying methods. With decreasing residual solvent content, the solvent removal became significantly slower as the diffusivity in the PLGA matrix decreased due to a decreasing plasticizing effect and free volume. A higher molecular weight and end-capping of PLGA increased the residual solvent content due to an increasing affinity for dichloromethane, viscosity and droplet/particle size. Increasing the lipophilicity of PLGA with a higher lactide content did not increase the residual dichloromethane content because a slower droplet solidification facilitated the final solvent extraction. The removal of residual dichloromethane was more efficient with alcoholic wet extraction, followed by aqueous wet extraction at elevated temperature and vacuum drying of the microparticles. Aqueous wet extraction reduced the residual dichloromethane content of risperidone-loaded PLGA 503H microparticles to 2.43 % (w/w) (20 °C) and 0.03 % (w/w) (35 °C) in 24 h. The elevated temperature promoted the risperidone-caused degradation of PLGA resulting in visible microparticle erosion and a decrease of risperidone encapsulation efficiency from 88 % to 75 %. Early filtration and subsequent vacuum drying of the solidified microparticles prevented this unwanted erosion of microparticles and drug loss. The residual dichloromethane content in filtered PLGA 503H microparticles was only reduced from about 5 % (w/w) to 4.34 % (w/w) (20 °C) and 3.20 % (w/w) (35 °C) after 18 h vacuum drying because of the missing plasticizing effect of water. Redispersing filtered wet microparticles in alcoholic media improved the residual dichloromethane extraction. The potential of different extractants was explained by the Gordon-Taylor equation and Hansen solubility parameters. Short-chain monohydric alcohols decreased the glass transition temperature of PLGA more than polyhydric alcohols, water or dichloromethane. Ethanol had the greatest plasticizing effect of all investigated solvents. A higher chain length of monohydric alcohols increased the affinity to PLGA and thus the solvent absorption, but also the tendency of agglomeration of the microparticles. Extraction in methanol: or ethanol:water mixtures efficiently reduced the residual dichloromethane content from 4 - 7 % (w/w) to 0.5 - 2.3 % (w/w) within 1 h and 0.08 - 0.18 % (w/w) within 6 h. Increasing the alcohol content and temperature promoted microparticle aggregation and drug loss. An alcohol vapor-assisted fluidized bed drying process for microparticles was developed to avoid the loss of encapsulated drug and thus utilize the potential of alcoholic extraction of the solvent residues from the microparticles. By regulating the alcohol concentration and the temperature of the purge gas, the alcohol absorption and the residual solvent and alcohol removal were controlled. Methanol proved to be particularly efficient in the developed setup due to its high volatility, molecular mobility and PLGA-affinity. The absorbed methanol was easily removed by alcohol-free fluidized bed or vacuum drying. While alcohol-free fluidized bed drying decreased the residual dichloromethane content only from about 7 % (w/w) to 6.4 % (w/w) (18 °C) or 0.7 % (w/w) (45 °C) within 24 h, 140 mg/L methanol vapor in the purge gas decreased the residual dichloromethane content to 0.11 % (w/w) in 2 h and removed it completely within 6 h. Methanol vapor also removed efficiently residual ethyl acetate from the microparticles (0.11 % (w/w) after 6 h), which is an alternative PLGA solvent to dichloromethane. Encapsulated risperidone increased the methanol absorption and thus contributed to microparticle plasticization. A high initial residual water content, which favored microparticle aggregation, was completely removed in less than 1 h by alcohol-free fluidized bed drying, which enabled the subsequent alcohol vapor-assisted removal of the residual organic solvent. Alcohol vapor-assisted fluidized bed drying was introduced as a promising alternative to established residual solvent removal methods, accelerating microparticle preparation without negatively affecting drug loading or release profile. A continuous process for the preparation of monodisperse PLGA microparticles by microfluidic flow-focusing was developed as an alternative to the discontinuous preparation by the classical batch process. For methodological reasons, smaller O/W phase ratios (1:2 - 1:8) were used compared to the batch process (≥ 1:20). The resulting limited initial solvent extraction resulted in a low risperidone encapsulation efficiency of only 19 - 21 % at a theoretical drug loading of 30 %. The buffering of the continuous phase to alkaline pH increased encapsulation efficiency up to 93 % but led to a change in the microfluidic droplet formation and thus microparticle size. This could be counteracted by reducing the total flow rate and the amount of stabilizer in the continuous phase. The in-vitro release of risperidone was delayed from microparticles prepared by microfluidic compared to similar-sized polydisperse microparticles prepared by the batch process probably because of a more homogeneous drug distribution within the PLGA-matrix. A continuous dilution-based solvent extraction process was developed, and the effect on droplet shrinkage examined with flow microscopy. A phase ratio of at least 1:100 after dilution and a sufficient extraction time (75 s at 1:100 and 15 s at 1:500) were necessary to shrink the droplets to the particle size of the final microparticles. Increasing the temperature or adding methanol to the continuous phase improved the dichloromethane extraction but impaired the process stability due to the formation of gas bubbles or sticking of droplets/particles. A tangential flow filtration (TFF) process was developed to separate the dichloromethane-enriched continuous phase from the microparticles. In conclusion, the effect of various formulation and process parameters on the removal of solvents in extraction/evaporation methods and on critical properties of the final microparticles such as drug loading and drug release was investigated. Methods were developed which accelerate both the initial and final removal of the organic solvents, thus shortening the total process time. In addition, high encapsulation efficiencies and desirable drug release profiles (e.g., low burst release) were achieved. This research contributes to know-how in the manufacturing of biodegradable PLGA microparticles by the solvent extraction/evaporation method through a detailed investigation of various single and combined solvent removal processes and their effects on the resulting properties of PLGA microparticles.
View lessZwischen Mitte der 1840er-Jahre und dem Deutsch-Französischen Krieg von 1870/71 avancierte der Kurort Baden-Baden zum führenden Modebad Europas und zu einem bedeutenden interkulturellen Zentrum. Der ausgeprägte französische Einfluss brachte der Stadt auf beiden Seiten des Rheins den Ruf einer "französischen Kolonie" und einer "Filiale von Paris" ein, wobei dies unterschiedlich interpretiert wurde. Die vorliegende Dissertationsschrift geht der Entwicklung dieses einzigartigen Ortes der deutsch-französischen Kulturbeziehungen im Spannungsfeld zwischen Kosmopolismus und erstarkendem Nationalismus nach. Sie analysiert die vielfältigen Faktoren, die zur Entstehung der "Sommerhauptstadt Europas" beitrugen, und identifiziert Phänomene und Grenzen des Austauschs und Kulturtransfers, welche die gesamte Bäderkultur prägten.
View lessThe satellite gravimetry missions GRACE and its successor GRACE-FO measure large-scale mass redistributions in the Earth system, including changes in terrestrial water storage, ice shelves, the oceans and atmosphere as well as the solid Earth. As the measurements are typically accumulated over one month before the computation of a gravity solution, high-frequency mass variations need to be accounted for using a-priori background models. The Atmosphere and Ocean Dealiasing Level 1B (AOD1B) data product routinely provides the necessary simulated non-tidal mass variations in the atmosphere and oceans. While progress towards better background models has been made over the past years, residual errors in the simulated atmospheric and oceanic mass variations are still among the largest limiting factors to the overall GRACE accuracy. As a result, further improvements of these data-products are directly linked to improvements in the final gravity solutions and thus subsequent geophysical analyses. This thesis summarizes the most recent improvements to the AOD1B product, including an updated ocean model configuration considering the effects of self-attraction and loading, an updated atmospheric component as well as an improved post-processing and tidal analysis. All of these changes are shown to result in a better representation of the simulated mass variations and are thus combined into a new release RL07 of AOD1B. Additionally, the new release is examined in terms of its stability and consistency over long and short time-scales. Spurious trends, low-frequency signals or bias jumps in the background model data can, if unaccounted for, introduce biases into the global gravity solutions which are prone to be interpreted erroneously in subsequent geophysical analyses. Consequently, the analysis focuses on signals that might be induced into the final gravity field solutions such as trends but also possible discontinuities caused by changes is the employed atmospheric datasets. It is shown that AOD1B RL07 is free from such artifacts and can thus safely be used as a background model in satellite gravimetry. Finally, an analysis of the residual errors in AOD1B RL07 is presented. The estimation is based on ensemble statistics derived from different atmospheric reanalyses. For the oceans, the impact of both the forced and intrinsic variability is investigated through differences in simulation experiments. The atmospheric and oceanic information is then combined to produce a new time-series of true errors, called AOe07, which is applicable in combination with AOD1B RL07 and can be used both as stochastic information in the gravity field retrieval process, as well as in simulation studies in preparation for future satellite gravimetry missions.
View lessNeurotransmission, essential for sensory perception, motor control, cognition, and behavior, occurs at synapses, where neurotransmitters are released from the presynaptic neuron into the synaptic cleft, triggering responses at the postsynaptic cell. At chemical synapses, neurotransmitter release involves the fusion of synaptic vesicles (SVs) with the presynaptic membrane, necessitating compensatory membrane retrieval, termed synaptic vesicle endocytosis, to reform and refill SVs for subsequent fusion cycles. Despite the recognized role of the Actin cytoskeleton in synaptic vesicle endocytosis, the precise mechanisms governing Actin polymerization and its function within presynaptic nerve terminals remain poorly understood. Here, we delineate the pivotal role of Actin regulatory diaphanous-related formins mDia1/3 and small Rho GTPases, RhoA/B and Rac1, in orchestrating synaptic vesicle recycling at rodent central synapses. Employing optical recordings of presynaptic membrane dynamics, ultrastructural and proteomic analyses, in combination with genetic/pharmacological manipulations, we demonstrate that mDia1/3 localize to the presynaptic membrane, proximal to the endocytic machinery, and govern the formation of presynaptic filamentous Actin structures (F-Actin). Loss of F-Actin due to perturbation of mDia1/3 results in significant alterations in presynaptic architecture, impacting plasma membrane homeostasis. Furthermore, our findings highlight that in the absence of mDia1/3, downregulation of RhoA and activation of Rac1 drive a compensatory response to mitigate the disruption of formin-mediated Actin dynamics. Besides modulating Rho GTPase signaling, we find that mDia1/3 negatively regulate the complex signaling network mediated by the mechanistic target of rapamycin complex 2 (mTORC2). We identify mTORC2 activation to be inversely coupled to the kinetics of SV recycling, likely through the modulation of cytoskeletal dynamics. In conclusion, our study elucidates that the endocytic cytoskeleton is governed by interdependent signaling pathways involving the small Rho GTPases RhoA/B and Rac1, as well as the action of mDia1/3 formins, operating within feed forward loops. The dynamics of the Actin cytoskeleton integrate mechanical regulation of synaptic membrane morphology with biochemical signaling mediated by mTORC2 and Rho GTPases to orchestrate the kinetics of synaptic vesicle endocytosis.
View lessThe discovery of useful molecules and new molecular phenomena is one of the cornerstones of human progress. Until the last two centuries, this process was largely driven by empirical evidence and serendipitous discovery. The understanding of physical phenomena at the macro level, driven by Newtonian mechanics, electromagnetism, and thermodynamics, and at the micro level, driven by quantum mechanics, has allowed for a more targeted approach to the discovery of new functional molecules for various applications. Despite these advances, the pace at which such molecules are discovered lags behind the rate of demand for green catalysts, sustainable materials, and effective medicines. A significant factor influencing this is the vastness of the chemical space of molecules. It has been approximated that within this chemical space, there exist approximately 1060 organic molecules (with a molecular weight less than 500, containing atoms H, C, N, and S). This count will be several magnitudes higher if larger molecules and extended structures are taken into account. Cataloging the properties of these molecules is not currently possible with our computational existing capabilities, but it is essential to find better materials and more effective drugs. As a result, the search for methods that can help speed up the assessment of the properties of molecules and accelerate the discovery of new molecules is an issue of paramount importance in modern chemistry. Machine Learning (ML) algorithms for predicting chemical properties represent an important step in this direction. Not only are ML algorithms capable of learning accurate structure-property relationships, but they are also faster than experiments or quantum chemical simulations. Furthermore, some ML methods leverage the structure-property relationships learned from data to generate novel molecules with desired properties, providing a cost-efficient way to identify useful molecules for laboratory synthesis. The spectrum of a molecule is one such important molecular property that helps scientists identify different molecules without destroying them. Amongst the various techniques of spectroscopy, X-ray Absorption Spectroscopy (XAS) is a well established technique that provides information about the structure and composition of various materials. The identification of materials using XAS, however, is not straightforward and requires using a combination of experimental data and quantum-chemical calculations performed on large computing clusters. These computational evaluations are resource-intensive and one often needs several such calculations to achieve successful molecular identification. Access to methods that can accelerate the prediction of spectra through structure-property relationships in spectroscopy can greatly enhance the ability to identify compounds synthesized in laboratories. Therefore, a major part of this dissertation is dedicated to employing and understanding ML methods that speed up the prediction of spectra by learning structure-property relationships from data. This work lays a foundation for future applications, where ML models can be used in experimental setups to identify molecules from spectra without human intervention, thereby helping accelerate the synthesis and identification of novel compounds. One downside of ML applications is the lack of model interpretability, which decreases the trust of the end-users. Investigations in this dissertation focus on devising a technique that helps humans understand why ML models make certain predictions, thereby helping build trust between the ML model and its end user. The creation of chemical data for ML applications itself usually requires quantum chemical calculations that involve solving the Schrödinger equation. The time dependent Schrödinger equation (TDSE) helps understand the behavior of quantum systems and allows for the calculation of time-dependent properties of molecules. The area of research that concerns itself with techniques for solving the TDSE is termed quantum dynamics. Using computer simulations of numerical methods for solving this equation, researchers have modeled several quantum dynamical systems, which have improved our understanding of photo-catalysis (reactions driven by light), surface phenomena such as chemisorption, and chemical reaction pathways. The second part of this dissertation focuses on using ML methods to solve the TDSE. The TDSE, which is a partial differential equation (PDE) in space and time, is one of the many fundamental equations that help model the behavior of physical systems. Some other notable PDEs that play an important role in physics and engineering are the Navier-Stokes equation for modeling fluids, the Heat equation in thermodynamics, and the wave equation in acoustics. Numerical techniques for solving PDEs are based on the discretization of the coordinate space into finite elements. As the size and dimensions of the grids increase, these methods become computationally expensive. As a result, solving PDEs such as the TDSE for large molecular systems is computationally demanding or even impossible. Advances in ML for solving PDEs aim at accelerating the solution of PDEs through a data-driven approach. In the second part of this thesis, ML models were trained on simulation data from quantum dynamical systems. Once trained, these models are capable of providing accurate descriptions of the behavior of systems that were not seen during training. A key advantage of such methods is their ability to generate novel simulations accurately and at high speed. As a proof of concept, the work in this dissertation shows how this speed can be exploited for downstream applications in quantum dynamics.
View lessDie Untersuchungen heben die Bedeutung des Tierschutzes in der Fleischindustrie, insbesondere in Schlachtbetrieben hervor, und spiegeln die öffentliche Debatte über den Schutz der Tiere während des Transports und der Schlachtung wider. Bereits vor dem Transport haben die Haltung und der Gesundheitszustand der Rinder einen erheblichen Einfluss auf das Wohlergehen der Tiere. Im Schlachtbetrieb kann das Verhalten der Mitarbeiter:innen oder die baulichen Bedingungen und die damit verbundenen Auswirkungen Stress bei den Tieren verursachen. Studien haben gezeigt, dass Stress sowohl durch Verhaltensbeobachtungen als auch durch die Messung physiologischer Parameter bewertet werden können. Eine schnelle und effektive Betäubung ist ein wichtiger Aspekt des Tierschutzes. Leicht überprüfbare Indikatoren für die Bewusstlosigkeit, wie der unmittelbare Zusammenbruch nachdem Bolzenschuss, Verlust des rhythmischen Atmens und des Kornealreflexes, werden routinemäßig am Schlachtbetrieb überwacht. Andere Aspekte, wie die Messung von Stresshormonen im Blut oder die Verwendung eines Elektrokardiogramms während der Betäubung, bieten wissenschaftliche Informationen für die Bewertung von Stress, sind aber in der Praxis nicht routinemäßig umsetzbar. Schulungen für Tiertransporteur:innen und Schlachthofmitarbeiter:innen tragen erheblich zur Stressreduzierung während des Umgangs mit Rindern bei, was wiederum das Wohl der Tiere während des Transports und der Schlachtung sowie die Fleischqualität verbessert. In einer Studie wurden zwei mehrsprachige Online-Schulungsmodule zur Schulung von Mitarbeiter:innen in deutschen Rinderschlachthöfen auf den Gebieten Tierverhalten und Umgang mit Rindern entwickelt und getestet. Die Teilnehmer:innen bewerteten das Programm positiv und die Ergebnisse deuten darauf hin, dass E-Learning zur Verbesserung des Wissens beiträgt, insbesondere wenn es auf Video-basiertem Lernen basiert. Die Untersuchung zeigte, dass es Verbesserungen in den Testergebnissen vom Prä- zum Post-Test in beiden teilnehmenden Gruppen gab. In einer weiteren Untersuchung wurde die gleiche Online-Schulung und deren Implementierung von Tierschutzbeauftragten und amtlichen Tierärzt:innen getestet und evaluiert. Die 25 an der Umfrage teilnehmenden Personen gaben den Schulungsmodulen hinsichtlich des Designs, der Lerninhalte und der Benutzerfreundlichkeit eine positive Bewertung. Insgesamt zeigen die Untersuchungen, dass gezielte Online-Schulungsprogramme das Potenzial haben, das Tierwohl zu fördern, Stress für Mitarbeiter:innen und Tiere zu reduzieren und die Arbeitsbedingungen insgesamt zu verbessern. Hier besteht die Notwendigkeit weiterer Forschung und Entwicklung von Online-Schulungsmodulen, um die Standards im Tierschutz während des Transports und der Schlachtung weiter zu verbessern.
View lessVivianite, a hydrated Fe(II) phosphate (Fe3(PO4)2·8H2O), is a mineral found globally in anoxic lacustrine or marine sediments, soils, associated with organic matter and in groundwater streams. It is a key phase controlling the cycling and immobilization of Fe(II) and phosphorus in these systems. Vivianite formation can aid in phosphorus recovery from wastewater; therefore, it is an important mineral for circular economy applications. This dissertation presents novel insights into the intricate processes governing the nucleation, growth, and phase transformations of vivianite. The nucleation of vivianite occurs via a transient intermediate phase – amorphous ferrous phosphate (AFEP), via a nonclassical pathway. AFEP is a metastable precursor phase which has a distinctly different local structure and composition (Fe3(PO4)2·4.7H2O), compared to vivianite. Through laboratory experiments and ex situ techniques, I demonstrated that AFEP precipitates from supersaturated solutions, undergoes subsequent hydration and structural transformations to transform into thermodynamically stable vivianite. The crucial role of water in this transformation is also highlighted. The stability of AFEP is inversely proportional to systemic (vivianite) supersaturation and temperature, suggesting AFEP occurrence to be a widely prevalent phenomenon in near-equilibrium (environmental) systems. Synchrotron-based small and wide-angle X-ray scattering experiments provide novel insights into the temporal evolution of vivianite crystallization via AFEP nanoparticles, with observations indicating concomitant processes of AFEP transformation and vivianite growth in solution – revealing a direct link between these two processes. Furthermore, the investigation of vivianite growth kinetics shows temperature-dependent dynamics, and a direct correlation between temperature and transformation rate. The rate of vivianite growth could be modeled via the JMAK model to derive the apparent activation energy (~ 51 kJ/mol) of this transformation. Temperature-dependent variations in crystal splitting also reveal new insights into varying vivianite crystal morphologies. Additionally, the thermally induced phase transformations of vivianite (amorphization and recrystallization into a distinctly new mineral phase), particularly under high-temperature conditions, including the critical influence of atmosphere on the resultant transformed phase compositions, is also reported here for the first time. This research provides new and significant insights for vivianite/mineral nucleation and growth mechanisms in aqueous solutions, materials synthesis and thermal stability of iron phosphates.
View lessThe topic of interoperability in healthcare has long been a topic of discussion and is examined in detail in this dissertation. A fragmented system landscape and the resulting data silos are among the reasons for the lack of interoperability. This shows that interoperability decisions are accompanied by economic challenges such as high costs and path dependencies as well as socio-technical challenges. The harmonization of data and its use for healthcare is attributed to electronic patient records and the platform ecosystems based on them. In combination with complementary services such as digital therapeutics, new forms of healthcare are emerging that present platform orchestrators with major challenges in interface management.
Clear requirements must be defined to support the resulting service bundles of innovative healthcare services on the platform. These challenges are further complicated by the different data quality requirements of the complementary value-added services. To address these complex requirements, this dissertation develops an interoperability maturity model based on a design-oriented approach that supports the targeted management of interoperability decisions by platform orchestrators. The model consists of five levels and includes seven dimensions of interoperability characterization. The maturity model is used to evaluate complementary services during integration and define requirements for the complementary services and integration profiles for the platform ecosystem. At the same time, the maturity model provides important impetus for the future development of the platform ecosystem and supports research in this area.
This cumulative dissertation consists of four published research articles that explore the topic of interoperability with different questions and research methods. From the perspective of interoperability management of platform ecosystems, three key findings emerge from the summary of the cumulative dissertation: First, this work shows that interoperability decisions are shaped by strong economic mechanisms, which are characterized and discussed in more detail in the thesis. Second, this thesis proposes the concept of patient-centered interoperability. This means that interoperability decisions are viewed more processually along care pathways to offer integrated digital service bundles on platforms for better care. The third core contribution is the developed maturity model, which supports platform operators in designing the interface requirements of the platform ecosystem. With the knowledge gained from the cumulative dissertation, the discussed aspects of interoperability can be better anticipated and addressed from both a research and a practical perspective, e.g., by platform orchestrators.
View lessDas Forschungsvorhaben ermittelte Anthelminthika-Resistenzen in Wiederkäuerbetrieben in Brandenburg, Sachsen-Anhalt und Mecklenburg-Vorpommern. In 12 Schaf- und 9 Rinderbetrieben wurden in den Jahren 2020 und 2021 Eizahlreduktionstests (EZRT) durchgeführt. In den Schafbetrieben lagen Resistenzen der Magen-Darm-Strongyliden gegenüber aller eingesetzten Anthelminthika vor: Fenbendazol (FBZ)-Resistenzen waren in sieben der acht und Ivermectin (IVM)-Resistenzen in allen acht getesteten Schafbetrieben nachweisbar. Eine unzureichende Wirkung von Moxidectin (MOX) wurde in acht der zwölf beprobten Betriebe beobachtet. In 5 Betrieben wurde somit eine Multiresistenz gegenüber aller drei untersuchten Wirkstoffen festgestellt. Ein in Betrieb 2 zeitlich versetzt durchgeführter EZRT mit Monepantel (MON) wies eine vollständige Wirksamkeit des Wirkstoffs auf. Die Anthleminthika-Resistenzsituation der Rinderbetriebe stellte sich weniger ausgeprägt dar: In zwei von acht Betrieben lag eine verminderte Wirksamkeit von FBZ vor. Eine Resistenz von Eprinomectin (EPR) lag in drei der acht Betriebe vor. Für das einmalig getestete IVM lag gleichfalls eine Resistenz vor. Damit war die Wirksamkeit in 2 Betrieben gegenüber aller eingesetzten Wirkstoffe reduziert. Die aus Drittlarven der Rinderbetriebe in-vitro durchgeführten Larvenmigrationshemmtests sprechen für die noch vorhandene Suszeptibilität von Levamisol (LEV) in allen acht eingeschlossenen Rinderbetrieben. Mittels deep amplicon sequencing gelang die Sequenzierung der in das Resistenzgeschehen involvierten Magen-Darm-Strongyliden Spezies der Schaf- und Rinderbetriebe mit insgesamt 29 Proben: Die Identifizierung der Spezies wurde für 11 Schaf- und 9 Rinderbetriebe vor der Behandlung, sowie in drei Schafbetrieben nach FBZ-Behandlung, in vier Schafbetrieben nach IVM-Behandlung, sowie in zwei Schafbetrieben nach MOX-Behandlung vorgenommen. In den untersuchten Schafbetrieben waren T. circumcincta, H. contortus und T. colubriformis am häufigsten vertreten. Resistenzen gegenüber FBZ, IVM und MOX wurden für H. contortus und T. circumcincta nachgewiesen, T. colubriformis wies Resistenzen gegenüber FBZ und IVM auf. Weitere Spezies blieben ebenfalls nach FBZ und IVM Behandlungen erhalten, darunter T. axei, T. vitrinus, C. curticei and C. fuelleborni. Die häufigsten Vertreter in den untersuchten Rinderbetrieben waren O. ostertagi und C. oncophora. In allen neun Nachbehandlungs-Proben der Schafbetriebe verblieben T. circumcincta. Trichostrongylus colubriformis war in 100 % der IVM- und FBZ-Nachbehandlungsproben vorhanden, jedoch nicht in den Proben nach MOX-Behandlung. Haemonchus contortus war in den Nachbehandlungsproben in drei der vier Betriebe vorhanden. Trichostrongylus vitrinus war vor Behandlung in geringen Anteilen in drei der vier Proben vorhanden. Diese Art verblieb zweimal nach IVM-Behandlung. Die FBZ-Behandlung war in einem von drei Fällen erfolgreich. Das Vorkommen von C. ovina war in allen Nachbehandlungsproben nicht mehr nachweisbar. Trichostrongylus axei war in geringem Maße ebenfalls in zwei Betrieben vorhanden und das Vorkommen dieser Spezies reduzierte sich nach IVM-Behandlung nur in einem der beiden Fälle.
View lessThis thesis is devoted to the investigation of previously unknown molecular iridium compounds with the iridium center in high oxidation states. The species were stabilized using matrix isolation technique and characterized by IR spectroscopy combined with state-of-the-art quantum-chemical calculations to analyze their electronic structures. It is well-known that the reaction of laser-ablated transition metal atoms with F2 or OF2 is particularly useful for the generation of interesting species containing metal atoms in high oxidation states. Iridium oxyfluorides (OIrF, OIrF2, and FOIrF) were prepared for the first time by the reaction of laser-ablated iridium atoms with OF2. Their assignment was based on the metal–oxygen and metal–fluorine stretching vibrations with characteristic 16/18O isotopic shifts. Quantum-chemical calculations provide a better understanding of Ir-O bonding in iridium oxyfluorides, and further compare the metal–oxygen bonding characteristics with similar compounds of group 10 and 11 metals to reflect trends in the bonding of the oxo ligand. Additionally, different iridium fluorides were obtained as side-products. These were further investigated in the analogous reaction of Ir with F2, yielding a series of molecular iridium fluorides IrFn (n = 1-6), while IrF7 was not detected. Since fluorine is a neat element, the photo-initiated defluorination of IrF6 was performed to support their assignment of the low-valent fluorides. The Ir-F stretching vibrations of a series of binary iridium fluorides were utilized for gaining an insight into their molecular structures. Among the observed iridium fluorides, IrF5 is one of the very rare examples whose structure was found to be significantly affected by spin– orbit coupling (SOC) and was confirmed experimentally. To further explore the higher-valent iridium fluorides, the reaction of IrF6 with laser-ablated alkali metal fluorides MF (M = Na, K, Rb, Cs) was investigated. This reaction led to the first observation of molecular iridium fluoride anions IrF5-, IrF6-, and a sequence of molecular alkali ion pairs M[IrF6] with M = Na, K, Rb, and Cs. Such IrF5- and IrF6- anions were also obtained by exposing IrF6 to laser ablation of metals (Ir or Pt) as electron sources. The IrF6- anion adopts an Oh structure in a closed-shell ground state stabilized by the SOC effect, rather than a distorted D4h structure in a triplet ground state as predicted by scalar-relativistic calculations. The closed-shell M[IrF6] ion pairs in C3v symmetry are stabilized by an alkali metal coordination to three F atoms on one face of the anion and their structural change from M = Na to Cs was spectroscopically confirmed.
View lessThis thesis is based on the examination of more than 18,000 photographs taken by participants of German expeditions to the Hindukush and Karakoram in the years between 1954 and 1963. I posit that a thorough analysis of these photographs facilitates a deeper understanding of the crucial role played by visual materials in the production of knowledge about geographical space. Furthermore, I argue that the 20th-century expeditions to the Hindukush-Karakoram can be characterised as ‘visualisation projects’. By using photography, German expedition travellers significantly shaped the contemporary perception and geographical imagination of the region as a high mountain space. Photo collections of three major German expeditions are examined as case studies: the 1954 German-Austrian Himalaya-Karakoram expedition, the 1959 German Karakoram expedition, and the 1962/63 Stuttgart Badakhshan expedition. I have reviewed and evaluated these photographs within the context of contemporary concepts and perspectives in geography and anthropology. Thus, two often overlooked issues have been addressed: firstly, the history of scientific exploration during the latter half of the 20th century, and secondly, the major role played by expedition photography in creating and disseminating knowledge about high mountain spaces. This work contributes to the scientific and historical reappraisal of analogue photographic practices in high mountain research. It also assesses the historical and present value of expedition photographs in the contexts of research, archives, and museums.
View lessMental health care represents a major global health challenge in contemporary societies. The higher frequency of mental health issues in urban, compared to rural areas, gains particular significance in light of the world’s rapidly accelerating urbanisation. Therefore, it is essential to understand how urban and natural environments impact our mental and brain health. Research shows that exposure to nature, in comparison to exposure to urban environments, improves mood, reduces stress, as well as physiological indicators of stress. Yet, the neural mechanisms behind the effects of natural and urban environments are not well understood. First studies have indicated that living environments are associated with mental health, as well as with brain function and structure. However, due to the inherent limitations of cross-sectional studies, the causal relationship between physical environments and brain health remains unestablished. This dissertation consists of four publications investigating the short-term causal effects of exposure to natural and urban environments on stress, stress-related brain function and hippocampal structure. In Paper I (Sudimac et al., 2022) we examined effects of a one-hour walk in a natural versus urban environment on stress-related brain function. The results indicated that activity in the amygdala, a brain region associated with stress, decreased after the nature walk, whereas no significant change was noted after the urban walk. The findings suggest that exposure to nature may have beneficial effects on stress-related brain regions, potentially acting as a preventive measure against stress-related mental health issues. In Paper II (Sudimac & Kühn, 2022) we explored sex differences in the impact of a one-hour walk in a natural versus urban environment on amygdala activity. Our results revealed a decrease in amygdala activity following the nature walk exclusively in women, with no significant change observed in men. This outcome indicates that women may benefit more from exposure to natural environments and underscores the necessity of considering individual differences, like sex, in the neural responses to exposure to natural and urban environments. In Paper III (Sudimac & Kühn, 2024) we investigated the impact of a one-hour walk in a natural versus urban environment on the structure of the hippocampus. We observed an increase in the volume of the hippocampal subfield, subiculum, following the nature walk, while no significant change was observed after the urban walk (though the interaction did not withstand the Bonferroni correction). Since the subiculum plays a role in dampening the stress response via the hypothalamic-pituitary-adrenal axis, our findings suggest that exposure to nature might positively influence a brain region associated with inhibition of stress response. In Paper IV (Sudimac et al., 2024) we assessed the effects of a walk in residential natural versus urban environments on subjective and physiological indicators of stress in mothers and their infants. We found no significant differences between exposure to natural and urban environments in mothers’ self-reported stress or in the stress-related cortisol levels, in both mothers and infants. However, a reduction in cortisol in mothers and infants was observed after walks in both natural and urban environments, indicating that the act of walking in residential areas might have a calming effect, regardless of the environment. In summary, this dissertation reveals a seminal evidence for the potential benefits of short-term exposure to natural relative to urban environments on stress-related brain function and brain structure. Furthermore, it emphasizes the need to consider individual differences, like sex and age, in exploration of natural and urban environments on mental and brain health. In conclusion, this work contributes to the growing body of research on environmental neuroscience and has potential implications for urban planning and public health strategies aimed at mitigating stress and enhancing mental health in urban populations.
View lessPrevious research has identified a common expectancy system, termed the “inconsistency compensation approach”, which governs the activation of cognitive mechanisms in response to socially aversive events, such as exclusion and loss of control. However, the functional properties of the expectancy system, in particular, whether threats to subjective expectations are processed independently or interactively, remain underexplored. To address this gap, this dissertation utilizes a modified Cyberball paradigm to simultaneously induce and monitor two distinct social threats – loss of control and exclusion. This approach incorporates real-time assessment of expectancy states using event-related potentials (ERPs). The main aims of this dissertation are threefold: First, to determine the extent to which the social expectancy system predicts upcoming social interactions. Second, to examine how the temporal overlap between initial and subsequent threats affects expectancy. Third, to assess whether the prediction of the social expectancy system covers a spectrum from negative to positive social interactions. To achieve these aims, three studies have been designed. Studies 1 and 2 explore how the experience of one social threat predict the expectation of another. Specifically, Study 1 investigates whether the experience of loss of control affects the subsequent processing of exclusion within the Cyberball game. Study 2 reverses the order of social threats to examine how prior exclusion experiences affect the subsequent processing of loss of control. Results from these studies indicate that preexposure to one type of social threat reduces expectancy violations for another type of threat, as evidenced by attenuated P3 effects. This preexposure effect is consistent regardless of the order of the threats and is not influenced by the temporal overlap of the preexposure. In addition, self-report data from the first two studies show that cessation of preexposure reduces negative mood and perceived threat to needs at the transition to another threat. Study 3 examines the impact of loss of control on the processing of overinclusion in Cyberball to assess whether the prediction of the social expectancy model extends to sociometer theory as a whole. While ERP results indicate that an expectancy bias induced by preexposure to loss of control does not alter expectations in overinclusion scenarios, self-reports suggest that regaining control positively affects affective states and enhances the satisfaction of the basic need for belonging. These findings indicate that the processing of a social threat can reduce expectancy violations for subsequent threats, regardless of their sequence. Interestingly, the preexposure effect remains stable regardless of the temporal overlap of preexposure and does not span a spectrum from negative to positive social interactions. Furthermore, the observed effects on self-reports appear to be primarily associated with affective states induced by the cessation of preexposure, highlighting a significant emotional factor. Overall, this dissertation provides neural evidence for the prediction of expectancy violations in the domain of negative social interactions. Conversely, self-reports appear to be more influenced by affective states, highlighting the nuanced interaction between cognitive mechanisms and emotional responses in social interactions.
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