The main goal of this dissertation is to gain a comprehensive understanding of alexithymia and how well the original definition conceptualizes the difficulties related to alexithymia, using a large representative sample of mentally healthy people. The research this dissertation is based on consists three separate studies. First, to understand latent structures shaping the alexithymic population and whether psychological distress differs among the possible latent subgroups, we have conducted a latent profile analysis. In order to gain insight into alexithymia’s relation to stress-related psychiatric disorders, we investigated hypothalamic-pituitary-adrenal (HPA) system functioning through cortisol awakening response. Furthermore, we have looked at empathic ability as a key process in social interaction. The study consisted of tasks related to the cognitive and emotional components of empathy and subjective arousal, and captured related brain activity and skin conductance response. The main findings are:

• There are three distinct subgroups of high alexithymic individuals: the group with overall high scores but lower scores in externally oriented thinking style and in fantasizing proved to be distinct with much higher levels of psychological distress. • Alexithymic individuals showed a reduced cortisol awakening response, which is an indicator of a dysfunction in the basic stress-response of the organism. • In the brain imaging study, alexithymic individuals showed lower emotional empathy and subjective arousal. Lower emotional empathy was accompanied by a higher activation of vetrolateral prefrontal cortex (VLPFC) and left inferior frontal gyrus (IFG) and lower subjective arousal was accompanied by a lower skin conductance response.

These findings support the hypothesis that alexithymia is not only related to difficulties in identifying and describing emotions but also related to a dysfunction in basic emotional processes. Alexithymic individuals have altered HPA-system function, lower empathy towards others in distress, lower subjective arousal and these all are accompanied by higher levels of psychological distress. Finally, the dissertation discusses the implication of these findings on the original definition of alexithymia and psychotherapy of alexithymic individuals with mental disorders.

Since 2006, Egypt is facing huge challenges related to the spread of avian influenza viruses. This is partly due to the very high death toll of HPAI in poultry populations causing huge economic losses. The ability of some AI viruses to cross species barriers and invoke severe and often fatal illness in human beings causes further alert. Sequential introduction of new viruses and enzootic co-circulation of different AI subtypes and clades as well as presence of further avian respiratory pathogens, such as IBV and NDV, are at the basis of these problems. All previous efforts to eradicate and control AI in Egypt were unsuccessful. The main objectives of this study aim at providing an update of the epidemiological situation regarding AIV including molecular characterization, and genotyping and reassortment analysis of AIV subtypes circulating in poultry in Egypt between 2017 and 2019. In addition, an assessment was attempted of the role of co-infections with different AIV subtypes and/or other respiratory viruses such as IBV and NDV. As a prerequisite for such work, improved diagnostic tools were developed and evaluated for AIV detection. In Chapter 2.1, various combinations of co-infections in poultry flocks with three different AIV subtypes and other respiratory pathogens such as IBV and NDV were detected in 32 out of 39 farms examined. The percentage of AIV H9N2‐positive samples was high (27/39), and co‐presence of HPAIV H5N8 was detected most often (22/39). The previously dominating HPAIV subtype H5N1 was only infrequently detected. Sequence and phylogenetic analyses of the hemagglutinin gene showed that both H5 and H9 viruses were located at the tips of the respective cluster branches indicating ongoing genetic drift. Several coding mutations in the neuraminidase N2 hemadsorption site suggested some adaptation to mammalian hosts. Sensitive detection of H9N2 viruses by RT-qPCRs required an update of diagnostic tools. Examination of further Egyptian poultry samples collected in early 2019 from 11 commercial broiler chicken farms revealed the presence and circulation of new reassortant AI viruses (Chapter 2.2). This affected HPAIV H5N8 of which two different reassortants were characterized that had not been reported in Egypt before. Also, novel reassortant H9N2 viruses were detected in chicken holdings for the first time in Egypt. Most importantly, however, a novel reassortant HPAIV H5N2 was found on three chicken holdings in different areas of Egypt. The HA gene segment was donated from HPAI H5 clade 2.3.4.4b viruses whereas four genome segments (PB1, PB2, PA, and NS) originated from another novel reassortant H9N2 viruses first detected in pigeons. Other segments (NP, NA, M) were acquired from H9N2 viruses circulating in chickens in Egypt since 2010. The formation of new reassortants and subtype may cause further problems in diagnosis and control of these viruses. Real-time RT-PCR investigations substantiated the presence of HP H5N8 in 21 of a further 37 investigated flocks sampled in 2019 (Chapter 2.3). HPAIV H5N1 was detected no longer in any of those holdings. Full-genome sequencing of three H5N8 viruses revealed presence of amino acid substitutions in the M2 and NA proteins conferring resistence to antiviral drugs Amantadine and Oseltamivir. Apparently, these mutations were acquired during circulation in Egypt. Systematic reassortment analysis of all publicly available whole genome sequences of HP H5N8 (n=23), reassortant HP H5N2 (n=2) and LP H9N2 (n=53) viruses from Egypt revealed presence of at least seven different genotypes of HPAI H5Nx viruses of clade 2.3.4.4b in Egypt since 2016. For H9N2 viruses, at least three genotypes were distinguishable. Heat mapping and tanglegram analyses suggested an annual replacement pattern of HP H5 genotypes. Several internal gene segments in both HP H5Nx and H9N2 viruses originated from AIV circulating in wild bird species in Egypt indicating local reassortment processes. Constant introduction of new AIV strains, reassortment leading to the generation of new subtypes and on-going genetic drift in AIV in Egypt called for a continuing update of molecular diagnostic tools. Based on the conclusions of this study recommendations for improved regulations and control of notifiable avian diseases in Egypt are provided.

Die Dissertationsarbeit befasst sich mit den Darstellungen von Opfergaben im Neuen Reich und ist geografisch auf den Raum Theben-West (Privat- und Königsgräber) begrenzt. Bei Band 1 handelt es sich um ein Nachschlagewerk, in dem die einzelnen Gaben anhand ihrer Produktion, Darstellung und symbolischen Bedeutung untersucht werden. Die Typologie in Band 2 dient der Identifikation von Opfergaben anhand ihrer Form bzw., falls möglich, ihrer Zugehörigkeit zu einer bestimmten Kategorie. Im Band 3 sind die Klassifikationstabellen, geordnet nach Opfergabekategorien, zusammen mit archäologisch nachweisbaren Funden aufgelistet. Zudem befinden sich alle Diagramme auf die in Band 1 verwiesen wird im Anhang. Bei Band 4 handelt es sich um den Katalog zur Arbeit, welcher alle bearbeiteten Opfertische mit ihren Darstellungen und einer Beschreibung enthält. Innerhalb der Arbeit wurde herausgestellt, dass der „archaisierende Opfertisch“ sowie die Darstellung von „Schnittgrün“ als Datierungskriterien verwendet werden können. Zudem befinden sich eine Entwicklungszusammenstellung der Opfertischszene im Neuen Reich und der Versuch einer Erklärung der Abwesenheit von Fisch und Schwein in jener Szene am Ende des ersten Bandes.

Somatosensory information is first detected by specialized sensory neurons in the periphery and then transmitted to the central nervous system (CNS) where sensory perception is formed in order to generate appropriate behavioral responses. The projections of afferents in defined layers of the spinal cord provide access to distinct neuronal pathway in the CNS, where spinal interneurons represent the first relay station controlling the coding of sensory stimuli. Despite its importance, little is known about the organization of spinal circuits involved in the integration of distinct sensory information. Here, we took advantage of the ability of the rabies virus to move from sensory neurons in the anterograde direction to directly link sensory modalities with its output connectivity (Zampieri et al., 2014). We used mouse genetic to conditionally express histone-tagged GFP, TVA receptor and rabies glycoprotein G (Rosa-HTB: Yan Li et al., 2013) under the control of Cre-recombinase activity. As proof of principle we focused on proprioception using the PV::cre mouse line to target proprioceptive sensory neurons (Hippenmeyer et al., 2005) and we performed stereotactic rabies injections (RVDG-mCherry/EnvA) in the spinal cord of PV::cre +/- ; Rosa-HTB f/f mice. We successfully obtained highly reproducible distribution patterns of connected neurons consistent with the known trajectory and termination of proprioceptive afferents in the spinal cord. In addition, we used this method to trace from a different sensory modality, focusing on Trpv1::cre mouse line known to label nociceptive/thermosensitive sensory neurons (Mishra et al., 2011). Comparing those sensory modalities, we observed a distinct laminar distribution pattern of second order neurons involved in proprioception and nociception reflecting the specific termination pattern of the sensory afferents in the spinal cord.

In contrast to complex varieties, a real algebraic variety X embedded in euclidean space can still be smooth at a singular point, in the sense that X is locally an analytic submanifold of the ambient space. This happens because the analytic Nullstellensatz does not hold for real analytic varieties, i.e. parts of analytic branches of X at p might not be visible in real space.

Identifying non-manifold points of real algebraic sets requires a novel approach and theory from analytic and real algebraic geometry. We will present several results to (dis)prove smoothness and also address the problem to check those criteria algorithmically. Based on those results we have implemented a Singular-procedure for algebraic curves.

As an application we will determine all configuration space singularities of several well-known kinematic linkages.

Das wissenschaftliche Arbeiten untersuchen kultur- und migrationsbezogene Einflussfaktoren auf die psychische Gesundheit bei Menschen mit vietnamesischem Migrationshintergrund in Deutschland. Aktuell über ein Viertel der Einwohner in Deutschland hat einen Migrationshintergrund. Menschen mit Migrationshintergrund, gerade wenn sie selbst migriert sind, bringen nicht nur ihre Sprache, sondern auch ihre Einstellungen, Werte und Verhaltensrepertoires, wie Gesicht wahren, Schamverhalten mit. In Bezug auf das psychische Gesundheitsverhalten auch im Züge des Akkulturationsprozess, sind hiermit nicht nur unterschiedliche Erwartungen und Krankheitsmodelle verknüpft, sondern auch Sorgen vor Diskrimierung und Stigmatisierung bei Inanspruchnahme psychiatrischer Hilfe. Diese Aspekte machen detaillierte Untersuchungen unter Berücksichtigung der kulturellen Diversität von Patienten notwendig, die weit über eine allgemeine Zuschreibung eines Migrationshintergrunds hinausgehen. 2010 eröffnete an der Klinik für Psychiatrie und Psychotherapie, Charité Campus Benjamin Franklin eine Spezialambulanz für Vietnamesische Migrant*innen. Ausgehend von dieser Pionierarbeit, konnten wir in den letzten 10 Jahren ein psychiatrisch- psychosoziales gemeinnahes Versorgungsnetzwerk als Teile der Regelversorgung für Menschen mit vietnamesischen Migrationshintergrund aufbauen (http://www.netzwerk-vietpsygesundheit.de). In diesem Rahmen konnten wir wissenschaftlich zeigen, dass unterschiedliche Erklärungsmodelle psychischer Störungen das Hilfesuchverhalten und die persönlichen Empfehlungen innerhalb der vietnamesischen Communities beeinflussen könnten. Unsere Längschnittuntersuchung der Inanspruchnahmepopulation seit Eröffnung der Spezialambulanz, konnte darauf hinweisen, dass sprach- und kultursensitive Therapieangebote zu einer deutlichen Zunahme von Akzeptanz und Senkung der Schwelle zur psychiatrischen Inanspruchnahmeverhalten führen könnten. Bei der Untersuchung kultureller Einflüsse auf die Symptomwahrnehmung im Vergleich mit deutschen Patient*innen, zeigten vietnamesische Patienten ausgeprägtere somatische Symptome, vor allem Schmerzsymtomatik und ein anderes Beschwerdemuster z.B. bei Angstsymptomatik mit Bauchschmerzen. Die Untersuchung des Wechselspiels zwischen Akkulturationsstilen und der Depressivität bei Patient*innen mit vietnamesischem Migrationshintergrund, zeigte klar, dass der Akkulturationsstil der Marginalisation beider Kulturen mit den schwersten Depressionssymptomen assoziiert war. Dabei stellt auf der Verhaltens- und Einstellungsebene diese Marginalisation eine psychotherapeutisch beeinflussbares Zielverhalten dar, um einen resilienzfördernden integrativen Akkulturationsstil zu entwickeln. In unserer quantitativen Untersuchung wurden mangelnde Deutschkenntnisse, Sehnsucht nach der Familie in Vietnam und Schwierigkeit bei der Anpassung an die deutsche Gesellschaft als die häufigsten Belastungen angegeben. Ergänzend zu solchen quantitativen Untersuchungen konnten wir seit 2015 im Rahmen unseres psychiatrisch-anthropologischen Teilprojekts des Sonderforschungbereichs Affective Societies, das mittlerweile in der 2. Laufzeit gefördert wird, innovative transdisziplinäre mixed-method Ansatze in die klinische Forschung der emotionalen Belastungsfaktoren integrieren. Zusammenfassend erstrecken sich die Vorarbeiten im Rahmen der Habiliationsschrift auf die Verbesserung der klinischen Versorgung, dem Verständnis kultureller Faktoren bei psychischen Störungen aber auch die Netzwerk- und Öffentlichkeitsarbeit. Diese Erfahrungen fließen mittlerweile auf internationaler Ebene in die Weiterentwicklung eines psychiatrisch-psychotherapeutischen Netzwerks in Vietnam ein. Hier konnten bereits eine Klinikpartnerschaft und zuletzt eine breit angelegte Partnerschaften für den Gesundheitssektor in Entwicklungsländern als PAGEL Hochschulkooperation zwischen der Charité und der Hanoi Medical Universität aufgebaut werden.

The controlled parenteral drug delivery of drugs is advantageous due to lower fluctuations of drug plasma concentrations and reduced injection frequency, resulting in an improved safety and efficacy of the drug product for the patient. The incomparable biodegradability and biocompatibility of poly(lactide-co glycolide) (PLGA) and the feasibility of controlling the drug release over days up to several months explains its common use as the polymeric matrix for such controlled parenteral drug delivery systems. Solid implants and microparticles represent common PLGA controlled drug delivery systems. In contrast to implants, microparticles can be administered without surgery, thus increasing the patient’s compliance. The preparation methods, however, require high effort in terms of process development and control. There are two most common methods for the microparticle preparation: The organic phase separation method and the solvent evaporation method. The aim of this work was to study in detail the parameters which affect these processes at every stage to improve their robustness and to solve associated limitations.

The microparticle preparation process by organic phase separation was investigated in detail with the objective of improving the process robustness (Chapter 3.1). The preparation method mainly consists of three steps: First, the drug is dissolved, dispersed or emulsified in a polymer solution (i.e. PLGA in methylene chloride). To this, a non-solvent (e.g. polydimethylsiloxane) is added to induce a liquid-liquid phase separation, resulting in a polymer-rich (dispersed) and polymer-poor (continuous) phase. The polymer-rich (coacervate) droplets are then hardened in silicon oils (e.g. octamethylcyclotetrasiloxane) or alkanes (e.g. hexane or heptane) by methylene chloride extraction. The formation of a stable coacervate phase is the core of the microparticle forming process, which is mainly characterized by the non-solvent concentration in the ternary mixture. The concentration of the non-solvent required to meet the stability window of coacervate droplets, where no sticking occurs, is commonly determined by optical microscopy. This study showed a lack of reproducibility of the conventional method due to occurrence of solvent evaporation, unstirred state, and a subjective evaluation of the microscopical appearance which lead to results highly dependent on the sample preparation and/or the operator. To improve the method reliability, additional macroscopical investigations of the polymer-poor and polymer-rich phase and coacervate resuspendability as a function of the non-solvent concentration have been suggested, since both indicate the limits of the stability window. A novel in situ method which allowed for the determination of the stability window under simulated process conditions was investigated. The closed, miniaturized system was equipped with an overhead stirrer, temperature control, camera (visualization probe) and an LED plus photosensor for real time transmission measurement. With the in situ method, the stability window was broader which was confirmed by the successful preparation of microparticles at non-solvent concentrations which were previously considered unfeasible based on the conventional stability window determination. Higher non-solvent concentrations were found in general to be advantageous to obtain a stable coacervate, leading to decreased collision frequency and coalescence efficiency. Increased mean theoretical distance between the coacervate droplets from 8 µm to 71 µm and 112 µm were calculated for 20, 40 and 45 % polydimethylsiloxane used. The theoretical calculations were confirmed by measurement of the actual distances between droplets obtained from the in situ appearances, and the transmissivity of the coacervate emulsion. Thus, by increasing the polydimethylsiloxane concentration from 36 % to 51 %, the stability of the emulsion was improved by factor 2.4 and 4.1 for 6 % and 3 % PLGA concentration, respectively. Finally, the dependencies of coacervate phase formation on temperature, polymer concentration and non-solvent addition rate could be established by applying the novel in situ method. To improve the drug distribution of water-soluble drugs within the polymer matrix, a primary W/O-emulsion is commonly applied. The smaller the droplets of the primary emulsion, the lower the initial drug release from drug-loaded microparticles. Key parameters were identified influencing the droplet size distribution of the primary emulsion. To obtain small droplet sizes, reduced solid content of the aqueous phase, increased stirring efficiency, and increased solid content of the organic phase should be considered. The effect of the hardening bath on the methylene chloride extraction was also investigated. With increasing methylene chloride affinity to the hardening agent and increasing hardening bath temperature, the methylene chloride extraction speed increased, thus shortening the hardening time. Furthermore, the common step-wise transferal of the coacervate phase to the hardening phase is critical. With progressing transfer, the emulsion volume decreases, causing changes in stirring geometry and, thus, droplet sizes. The influence on the homogeneity of the batch is expected to increase with scale-up. Thus, a continuous production set-up for the coacervate phase by static mixing was developed and investigated. The particle size could be controlled by polymer concentration and total flow rate, while it was independent of the phase ratio between PLGA solution and non-solvent, and of the drug loading. A scale-up by factor 10 did not influence critical quality attributes of microparticles and thus demonstrated the suitability of the novel continuous coacervate production method.

A drawback of the microparticle preparation process by organic phase separation is the risk of volatile (methylene chloride, octamethylcyclotetrasiloxane) and non-volatile (polydimethylsiloxane) residual solvents, the monitoring of which is of high importance in process development and control due to the inherent toxicity for the patient, as well as the possible influence on critical quality attributes of the product. Gas chromatography (GC) is recommended for the quantification of residual volatile solvents in pharmaceutical products, but no method is currently available for the simultaneous quantification of the non-volatile silicon oil polydimethylsiloxane in presence of the volatile silicon oil octamethylcyclotetrasiloxane. An H-NMR method was successfully developed and validated to simultaneously quantify volatile and non-volatile organic solvents and silicon oils appearing as residual solvents in microparticles prepared by organic phase separation (Chapter 3.2). Accuracy, precision, specificity, linearity, range, limit of detection and quantitation and robustness were investigated and agreed with validation requirements. The H NMR method was less sensitive regarding the methylene chloride-, but more sensitive regarding the octamethylcyclotetrasiloxane-quantification compared to the compendial headspace gas chromatography. Additionally, with H-NMR it was possible to quantify volatile and non-volatile compounds simultaneously, at lower sample preparation effort and material consumption than with the compendial method. The method suitability is expected to apply for all excipients being soluble in deuterated solvents used for analysis, provided that obtained peaks do not overlap. Furthermore, the sample preparation for H NMR measurement was simpler and less prone to systematical mistakes. The measurement by standard addition, needed for GC, increased the sample preparation steps, thus increasing the effort in terms of time and costs and increasing the number of sources for mistakes. Due to the sample preparation based on weight (H NMR) and not on volume (GC), a lower influence is expected for the processing of volatile organic compounds.

With the H-NMR method, the influence of formulation and process parameters on residual solvents in PLGA microparticles prepared by organic phase separation was studied (Chapter 3.3). Microparticles were prepared by using the volatile methylene chloride as the organic solvent, the non-volatile silicon oil polydimethylsiloxane as the non-solvent and the volatile silicon oil octamethylcyclotetrasiloxane or heptane as the hardening agent. In particular, investigations on the simultaneous appearance of two silicon oils in PLGA drug delivery forms have, up to now, not been extensively discussed in the scientific literature. Methylene chloride and polydimethylsiloxane residuals were reduced by decreasing the polymer concentration, increasing the hardening agent volume and increasing the hardening time, while they were increased by incorporation of a hydrophilic model drug. Additionally, methylene chloride residuals could be reduced by optimized drying conditions (vacuum, long drying times and drying temperature close to Tg). While methylene chloride residuals were independent of the hardening agent (octamethylcyclotetrasiloxane or heptane) and the polydimethylsiloxane addition rate, polydimethylsiloxane could be reduced by using octamethylcyclotetrasiloxane instead of heptane as the hardening agent and by decreasing the polydimethylsiloxane addition rate. Methylene chloride and polydimethylsiloxane residuals were independent of the coacervation temperature. Octamethylcyclotetrasiloxane residuals were also independent of the coacervation temperature. However, for the other parameters octamethylcyclotetrasiloxane behaved contrary to methylene chloride and polydimethylsiloxane. Residuals were reduced by increasing the drug loading, and increased by decreasing the polymer concentration, increasing the hardening agent volume and increasing the hardening time. Despite its volatility, octamethylcyclotetrasiloxane could not be decreased even under severe drying conditions. Nevertheless, it was superior compared to heptane due to an improved polydimethylsiloxane extraction and significantly lower residuals in the microparticles. Methylene chloride and polydimethylsiloxane are influenceable by comparable formulation and process parameters at the expense of octamethylcyclotetrasiloxane residuals, which were, however, acceptable for all investigated conditions showing residual levels of NMT 1 %.

For the preparation of microparticles by solvent evaporation, a drug-containing PLGA solution in methylene chloride is emulsified in an aqueous phase with a stabilizer. Methylene chloride is then evaporated to solidify microparticles. This method is advantageous due to lower organic solvent consumption, easier set-up and process control compared to the phase separation method, but drugs may diffuse out to the aqueous phase, causing low encapsulation efficiencies and high burst. Faster polymer precipitation by accelerated methylene chloride removal helps to solve these problems. Commonly, this is achieved by increasing the aqueous phase volume; however, large volumes are often unfavorable in industrial processes. To accelerate the methylene chloride removal while maintaining the aqueous phase volume at a minimum, the preparation temperature was increased above the methylene chloride boiling point, and the influence of increased temperature on drug-loaded microparticles was studied (Chapter 3.4). Interestingly, emulsified methylene chloride in a 1 % poly(vinyl alcohol) (PVA) solution showed a metastable, superheated state above its boiling point (39.6 °C) until a limit of superheat was reached, referring to the temperature where instant methylene chloride vaporization occurs. Thus, methylene chloride evaporation was slower than expected around its actual boiling point, and boiling was delayed to a 2 fold higher temperature (74-79 °C) compared to the pure solvent. Addition of a polymer to the dispersed phase further increased the limit of superheat to 84 °C, which was unfavorable for an accelerated methylene chloride removal. To test the influence of the solvent evaporation at elevated temperatures, PLGA microparticles were prepared at 25 °C, 55 °C, 75 °C and 95 °C and investigated in terms of particle size, appearance, encapsulation efficiency, residual solvents and drug release. The used model drug was soluble in methylene chloride. By increasing the temperature, the process time decreased from 12 hrs (25°C) to less than 1 min (95°C) independent of the drug loading. The particle size was only affected above the limit of superheat. Increasing the temperature to 95 °C decreased the particle size significantly by factors 15, 10 and 9 for 0, 10 and 30 % drug-loading due to an explosive methylene chloride vaporization sufficient for a droplet disruption. The encapsulation efficiency was first decreased at temperatures above the polymer Tg (45-50 °C). However, a further temperature increase to 95 °C fastened the methylene chloride removal to such an extent that accelerated polymer precipitation caused encapsulation efficiency to raise again. Residual solvents as well as the surface morphology were independent of the preparation temperature for all drug loadings. However, inner porosity depended on the preparation temperature. Increasing the temperature to 55 °C and 75 °C led to the formation of inner pores due to an expansion of gaseous bubbles which could not escape from the polymer matrix. In contrast to this, particles prepared at 95 °C were dense without inner voids. Drug release from the 10 % drug-loaded formulations was comparable for the formulations prepared at 25 °C, 55 °C and 75 °C, while for the formulation prepared at 95 °C the initial drug release was faster. However, drug release was completed within about 60 d for all preparation temperatures. Drug release from the 30 % drug loaded formulations was completed within 10-12 d for all preparation temperatures and was independent of PLGA hydrolysis. Results demonstrated that microparticles could be prepared at increased process temperatures, but that the accelerated methylene chloride removal is impeded by the presence of a metastable state and the limit of superheat, which influences critical quality attributes of the microparticles.

In conclusion, key formulation and process parameters affecting attributes of PLGA microparticles prepared by a phase separation method were identified, which are expected to improve the process robustness in future studies. Additionally, a novel analytical method was developed giving new insights on the effect of formulation and process parameters on residual solvent levels in these microparticles. Particularly, volatile and non-volatile silicon oils could be studied simultaneously. Furthermore, the methylene chloride removal rate during the preparation of microparticles by solvent evaporation increased with increasing temperature, but the energy needed to evaporate methylene chloride was much higher than expected due to the presence of a limit of superheat of the emulsion. Results contributed to the understanding of solvent evaporation process, potentially serving as the basis for future process optimization approaches by accelerated methylene chloride removal.

Some networks obtained from real world problems such as social networks, biological cells or earthquake recurrence networks, may consist of many thousands of vertices and exhibit a pronounced modular structure. To facilitate further analysis or derive a simple model of the whole system, it is often useful to identify subunits of these networks that are nearly disconnected from the remaining graph, called “clusters”. A well-known method to find clusters in undirected networks is based on random processes whose state space is the network's set of vertices, moving in each time step to a randomly chosen neighboring vertex. A close correspondence between network substructures and properties of such a random walk process has been exploited in numerical algorithms, which aim at decomposing the random walk's state space into disjoint “metastable” sets, describing nearly stable conditions of the system which are rarely changed. This dissertation contains an introduction to the theory of graphs and random walks, summarizes some popular cluster analysis methods and eventually presents and explores a new method which is based on random walks as well, but does not require the computationally costly approximation of eigenvectors. Instead, it uses “hitting times” that describe the expected number of time steps the random walk takes to enter a given target set. For the purpose of assessing runtime scaling, a family of sparse, directed, random networks spanning several orders of magnitude in vertex count is introduced. A series of tests verified that runtime of the presented algorithm scales linearly with the number of vertices in these network, in accordance with theoretical results. Therefore, the new approach is well suited for very large networks that are sufficiently sparse and shows a computational advantage over existing methods requiring eigenvector approximations. The presented method has one main caveat: The hitting times used in the detection of metastable sets are well-defined and finite only if each target set can be reached via a directed path from any vertex in the graph and the random walk is ergodic. This requires the graph to be strongly connected, which implies that it must be free of sinks and sources. Due to this restriction, many directed graphs are not eligible. The final discussion sketches an approach on how to overcome that limitation. Still, the set of strongly connected graphs is a significant extension of the set of undirected graphs, widening random walk based cluster analysis to an even broader field of application.

The GRACE and GRACE-FO satellites observe the redistribution of mass in terrestrial water storage, ice sheets, oceans, atmosphere, and solid Earth. Because GRACE data is typically accumulated into monthly-mean gravity fields, an a priori background model, namely the Atmosphere and Ocean Dealiasing Level 1B (AOD1B) product, is applied to remove non-tidal variability that would otherwise alias into the monthly solutions. The main disadvantage of AOD1B RL06 compared to its previous release is that it does not simulate the dynamics beneath the Antarctic ice shelves, which can have a strong influence on global ocean circulation. The primary motivation for this work is the development of the new release of AOD1B, but the performed model experiments can also provide useful insight into the influence processes in the Southern Ocean have on global ocean dynamics.

To be able to test various model experiments, as well as to compare GRACE gravity field solutions, validation against in situ measured ocean bottom pressure (OBP) is used. The validation is somewhat better suited for submonthly variability of the ocean models than for long-term signals measured by GRACE because the in situ time series are affected by the errors in trend and drift removal on longer temporal scales. The difference between the pointwise in situ and the area-averaging GRACE measuring technique also influences the comparison. It is shown that post-processing choices can severely impact the results of the validation of GRACE fields, so if different solutions are compared, their post-processing needs to be identical. Validation against in situ OBP is used to compare the EGSIEM combined GRACE solution with its five contributing datasets. It is shown that the combined solution is very close to the leading CSR RL05 and ITSG-Grace2016 solutions, outperforming the others. To investigate whether GRACE is able to detect submonthly signals, the ITSG-Grace2016 daily Kalman solution, from which the submonthly atmospheric and oceanic variability has been removed with AOD1B RL05, is validated against in situ OBP. The results show that GRACE successfully captures some submonthly variability that is not predicted by the incorporated dealiasing model.

As a first step towards AOD1B RL07, the dynamics beneath the Antarctic ice shelves are implemented into the model used as the oceanic part of AOD1B, the Max Planck Institute Ocean Model (MPIOM). The bathymetry is modified to include the areas under the ice shelves and two new model experiments are performed: in one those regions are treated as open ocean, while in the other the atmospheric forcing is modified to simulate the ice shelves. The changes caused by such modifications are not limited only to the Southern Ocean, but also affect the Northern Atlantic, confirming the role the Weddell Sea has on the meridional overturning circulation. While surface changes exceed the typical variability only in a few regions, the differences at the bottom of the ocean are larger. The changes caused by ice shelf forcing are of the same order of magnitude in the vicinity of the ice shelves, but much smaller globally. A comparison with the GLORYS2v4 ocean reanalysis shows that the new model experiments are closer to the reanalysis, especially in the regions where the original MPIOM experiment performs the worst. The analysis of OBP variability points out some possible issues that need to be fixed before publishing the new AOD1B release. Validation against in situ OBP, however, shows that the modifications are without a doubt in the right direction: the new model experiment has increased relative explained variances in the 1 - 3 days band by approximately 5 % throughout Pacific, and by more than 10 % in the Antarctic Circumpolar Current region.

Systems biology deals with the computational and mathematical modeling of complex biological systems. The aim is to understand the big picture of the system’s dynamics rather than the individual parts by integrating different sciences, e.g., mathematics, physics, biology, computer science, and engineering. In biological systems, mathematical models of biochemical networks are necessary for predicting and optimizing the behavior of cells in culture. Different mathematical models have been discussed, such as discrete models, continuous models, and hybrid models. In a discrete model, the biological system assumes discrete values. A continuous model uses a system of differential equations to describe the change of concentrations of substances in a cell over time. A hybrid model combines both discrete and continuous models. The main challenge in continuous models is to find the kinetic parameter values. In this thesis, we build a kinetic model of a metabolic-genetic network introduced in Covert et al., 2001 that mimics a discrete model of regulatory flux balance analysis (rFBA) which is based on steady-state assumptions. The kinetic model we introduce has unknown parameters, so it is necessary to perform parameter estimation techniques. We perform a parameter estimation technique using data sets generated from a simulation of the rFBA model. In nature, many phenomena of interest are high-dimensional and complex. Thus, model reduction is considered a vital topic in systems biology. Model reduction methods are mathematical techniques that aim to represent a high-dimensional, dynamical system by a low-dimensional system that roughly preserves the main features and characteristics of the original system. The idea of model order reduction is to use the reduced-order model instead of the full-order model in the simulation or optimization of the system to reduce the computational effort and the runtime of the simulations. In this thesis, we discuss two different model reduction methods. The first method assumes a time scale separation, i.e., it assumes two time scales, a fast time scale and a slow time scale, where the fast time scale dynamics converge to a quasi-steady state. The second approach, proper orthogonal decomposition, aims at obtaining low-dimensional approximate descriptions of high-dimensional processes while retaining the most important features of the dynamics. We apply these approaches to different biological system models from the BioModels database.

Lineage reprogramming of somatic cells to generate pancreatic β-like cells represents a promising strategy for developing a cell-based therapy to treat diabetes. The close developmental origin with the pancreas and its regenerative ability make the liver an ideal tissue source for generating new β-cells. We recently identified the transcription factor TG-interacting factor 2 (TGIF2) as a developmental regulator of the cell fate decision between liver and pancreas in the mouse. Consistently, stable lentiviral expression of TGIF2 is sufficient to promote a pancreatic progenitor state in adult mouse liver cells, by repressing the hepatic transcriptional program and initiating the pancreatic progenitor one. The studies of my Ph.D. thesis have focused on further investigating the biological function of TGIF2 in the mouse and translating these findings in human cells. Specifically, I undertook an in vivo loss-of-function approach based on the Cre/LoxP recombination system in the mouse to define the requirements of Tgif2 during pancreas embryonic development. Whole transcriptome analysis showed that TGIF2 acts as regulator of binary choices: first, it establishes and maintains pancreatic identity instead of a liver fate; secondly, it controls pancreatic endocrine lineage differentiation at expenses of the acinar one. These findings were further supported by in vitro reprogramming experiments, whereby enforced expression of human TGIF2 in human primary hepatocytes repressed the liver features and promoted the induction of a pancreatic state. Moreover, I expanded the study of TGIF2 reprogramming potentials to different cellular contexts, including fibroblast cells. Overall, the results presented in this work suggest a conserved function of TGIF2 in initiating a pancreatic program in different cellular contexts. Further comprehension of TGIF2 and the molecular mechanisms regulating pancreatic identity and cellular plasticity will ultimately lead to the development of innovative cell-based therapies to cure diabetes.

Storybooks and talk centered around shared reading contain more rare words, complex syntax, and narrative structures than the language that caregivers usually use when talking to children. Therefore, interactive storybook reading has the potential to facilitate children’s acquisition of lower level language (LLL) skills (e.g., vocabulary, grammar) and higher level language (HLL) skills (e.g., comprehension monitoring, narrative comprehension). This dissertation addresses gaps in shared storybook reading research pertaining to questions of assessment, intervention, and early literacy models. It investigates from a developmental and educational perspective how shared reading in the home literacy environment (HLE) and the child care literacy environment (CCLE) is related to children’s oral language skills. The first aim is to validate two recognition tests for German-speaking participants. This allows an objective and economic assessment of storybook exposure and adult literature exposure, both of which are related to children’s language development. The second aim is to clarify (a) the relation between parent and child as literacy agents in a home literacy model of shared reading, and (b) whether shared reading is related to children’s HLL skills besides being related to their LLL skills. The third aim is to test the effectiveness of a narrative dialogic reading intervention targeting LLL and HLL skills. To this end, four studies were conducted. Study 1 validated a storybook title recognition test (TRT) for German-speaking preschoolers and caregivers. The TRT captures relative differences in the amount of shared reading. In structural equation models, the TRT was a unique predictor of preschoolers’ language skills, explaining about 50% of variance in language skills. By contrast, questionnaire measures of socioeconomic status and home literacy environment did not explain additional variance in language skills. Study 2 validated an author recognition test (ART) for 13 to 80-year-old German-speaking readers. The ART is a measure of leisure reading that explains a substantial amount of variance in caregivers’ language skills, which is in turn related to children’s language development. Even though print exposure accumulates with time, several life span studies did not find a positive relation between reader age and ART scores. Study 2 used a sample of 13- to 77-year-old readers. The recognition probability of classic authors increased between ages 15 and 65. By contrast, the recognition probability of recent authors only increased between ages 15 and 45. The author mean publication year turned out to be a key variable for estimating print exposure in age-diverse samples. This author variable should be taken into account when modelling relationships between literacy environments and children’s language skills, especially if the age of caregivers varies (e.g., adolescent siblings, parents, grand-parents). Study 3 examined how HLE and CCLE are related to preschoolers’ storybook exposure and how the storybook exposure of preschoolers, parents, and child care workers is related to LLL and HLL skills. Parents’ exposure to storybooks was a unique predictor of children’s vocabulary and grammar skills. Parents’ storybook exposure was also moderately related to children’s storybook exposure, which in turn explained unique variance in vocabulary, grammar, comprehension monitoring, and narrative comprehension. Therefore, the storybook exposure of children and parents should be conceptualized as related, but separate variables in models of the home literacy environment. Moreover, models should differentiate between LLL and HLL skills as correlates and outcomes of shared reading. Study 4 developed a narrative dialogic reading intervention with wordless picture books that targeted preschoolers’ LLL and HLL skills. The intervention had small short-term effects on narrative comprehension and vocabulary skills. Comparisons with an alternative treatment and a no treatment group showed that the effects were due to the specific intervention contents. Individual differences in storybook exposure and general cognitive abilities did not moderate intervention gains. Children in control groups caught up after five months, with the exception of inferential narrative comprehension, where intervention effects were maintained at first follow-up. This indicates that narrative dialogic reading provided a unique opportunity to preschoolers for learning inferential narrative comprehension skills. In sum, this dissertation provides new methods and insights for the assessment of print exposure and shows that narrative dialogic reading fosters a broad range of oral language skills. Regarding the refinement of early literacy models, additional analyses showed that, above children’s and parents’ storybook exposure, the ART was a unique predictor of LLL skills. Parental leisure reading and shared storybook reading were connected to children’s oral language skills through multiple pathways that should be represented in early literacy models.

Viele Studien haben bisher das Bild des Orients und des arabischen Raums bei Goethe untersucht, wie Goethe die anderen Kulturen und Literaturen sah. Meine Arbeit jedoch nähert sich dem Thema erstmals, wenn man so will, von der anderen Seite. Denn sie steht unter den Leitfragen: Wie ist das Bild Goethes in der arabischen Welt konturiert? Wie wurde und wird Goethe in der arabischen Literatur dargestellt? Die vorliegende Studie untersucht die Schwerpunkte der arabischen Rezeption deutscher Literatur vom 20. bis zu den Anfängen des 21. Jahrhunderts, wobei insbesondere auf Johann Wolfgang von Goethe und seinen Briefroman Die Leiden des jungen Werthers Bezug genommen wird. Im Mittelpunkt steht dabei die Entwicklung der Rezeption, also die Interaktion zwischen Leser und Text, ohne dabei die Rolle des ursprünglichen Autors zu vernachlässigen. Als theoretische Grundlage der Forschung dient die Rezeptionstheorie von Hans Robert Jauß, in welcher der historisch-ästhetische Erwartungshorizont der literarischen Erfahrung im Zentrum steht, wobei das Werk-Rezipient-Verhältnis sowohl die Aktivierung wie auch die Obejktivierung dieser Erwartung umfasst. Der Schwerpunkt liegt dabei vor allem auf der Frage, wie die deutsche Literatur von den Arabern zunächst übersetzt und gelesen, insbesondere aber darauf, mit welcher Wahrscheinlichkeit sie gemäß ihren intendierten Aussagen rezipiert wird. So ist etwa die Arbeit des Übersetzers bei der Auswahl des zu übertragenden Stoffes sehr entscheidend. In der angemessenen Übertragung etwa bildlicher Sprache liegt auch ein schöpferischer Aspekt, und die Übersetzung literarischer Texte, für die ihre ästhetische Form konstitutiv ist, unterscheidet sich somit stark von Übersetzungen von Texten, bei denen die Vermittlung von Informationen im Vordergrund steht. Unter diesem Blickwinkel wird die Übersetzung selbst als Prozess der Rezeption betrachtet, im dem der Übersetzer als ein erster Leser fungiert, der vor allem die Wirkung des literarischenTextes mitrezipiert und innerhalb seines Kulturkreises angemessen wiederzugeben im Stande ist. Diese Form der "Nachbildung", trägt dazu bei, den Eigensinn der literarischen Form zu bewahren, damit er auch im arabischen Text noch wahrnehmbar bleibt. Die arabische Rezeption der deutschen Literatur stellt noch ein Desiderat der Forschung dar. Man interessiert sich stattdessen eher für die deutsche Literatur als einheitliches Forschungsgebiet. Schwerpunkte liegen dabei auf dem Fremdbild der eigenen Kultur, auf Goethes Konzept der Weltliteratur und auf dem breitgefächerten Interesse, das Goethe dem Orient entgegenbrachte.

Investigating the motion of electrons in atoms, molecules and solids on attosecond timescales is of widespread current research interest. In recent years, attosecond transient absorption spectroscopy (ATAS), has emerged as a versatile tool to study these dynamics. In ATAS the modification of absorption of an attosecond pulse in the extreme ultraviolet (XUV) wavelength region by a phase-locked infrared pulse (IR) is explored, revealing the dynamics of electronic coherences and light-induced couplings on attosecond timescales. To resolve the light-induced coupling of molecular valence and Rydberg states on the timescales of the cycle of the IR laser lightfield, an ATAS study on iodomethane is presented in the first part of this thesis. For the first time, ATAS is extended from atoms and homo-nuclear molecules to a polyatomic molecule, as well as to core-to-valence and core-to-Rydberg transitions in the XUV to soft X-ray spectral regimes that allow a site-specific insight into the molecular light-induced dynamics. The impact of symmetry on the observable coupling pathways in ATAS is unraveled and the possibility to obtain additional information from polar and chiral molecules in future experiments is discussed.

In the second part of this thesis, XUV refractive optics are developed using a dense gas jet. Refractive optics have so far been absent in the XUV region, due to a lack of materials with suitable properties. An XUV prism is introduced as the first demonstration of XUV refractive optics, based on the utilization of an inhomogeneous, dense gas jet. In a second application of XUV refractive optics, an XUV gas lens is constructed: A dense gas jet matching the XUV beam diameter is used to focus an XUV beam similar to the way conventional cylindrical lenses focus beams. Exploring the behavior of refractive indices in the XUV spectral domain a novel phase-matching concept is introduced that allows to efficiently modify and control the spectral bandwidth of an XUV source. The concept is experimentally demonstrated by means of XUV bandwidth compression in a krypton gas jet.

The results of the work reported in this thesis show how the complex transient dipole spectrum of atoms and molecules can be experimentally observed and theoretically understood from a transient absorption or refraction measurement and used to unravel dynamics on the attosecond timescale. The developed tools allow for a more versatile application of XUV spectroscopy in the future.

In dieser Arbeit wird der Einfluss von Nanostrukturen auf die Elektronendynamik in organischen und anorganischen Halbleitern mittels zeitauflösender Zwei-Photonen-Photoemission (2PPE) untersucht.

Im ersten Teil werden dünne Schichten des organischen Halbleiters a-Sexithiophen (alpha-6T) auf einem Au(1 1 1)-Substrat untersucht. Aufbauend auf vorangegangenen 2PPE-Untersuchungen an diesem Probensystem [1–3] stehen in dieser Arbeit die Bildungs- und Zerfallsdynamik von Exzitonen bei einer optischen Anregung 130 meV oberhalb des Exzitonenbandbodens im Zentrum der Betrachtungen. Dadurch soll geklärt werden, wie sich vibronische Anregungen auf die Exzitonendynamik auswirken. Dünne Schichten alpha-6T auf Au(1 1 1) wachsen bei Raumtemperatur in einem Stranski- Krastanov-Modus mit einer Benetzungsschicht von 2ML und anschließender Kristallitbildung. Thermische Desorptionsspektroskopie (TDS) ergibt, dass die in direktem Kontakt zum Metall stehende erste Lage eine Moleküldichte von 0,56 Moleküle/nm^{2} aufweist und nicht molekular desorbiert. Während a-6T auf einer Quarzoberfläche ein stark gekoppeltes H-Aggregat aus senkrecht stehenden Molekülen bildet, adsorbieren die Moleküle auf Au(1 1 1) mit der langen Achse überwiegend parallel zur Oberfläche. Differenzielle Reflexionsspektren im Energiebereich der S1-Bande von a-6T zeigen bei Multilagenbedeckungen charakteristische Merkmale eines HJ-Aggregates mit Kopplung an Vibrationsmoden. In den 2PPE-Messungen werden Exzitonen nur bei Bedeckungen beobachtet, die die Benetzungsschicht übersteigen. Sie entstehen durch direkte Photonenanregung im alpha-6TFilm. Die Evolution der asymmetrischen Peakform im 2PPE-Spektrum erlaubt Rückschlüsse auf die dynamische Entwicklung der Exzitonen. Die optisch angeregte Exzitonenpopulation relaxiert mit einer Zeitkonstanten von 70 fs zum Exzitonenbandboden. Die Entwicklung auf einer längeren Zeitskala von 1 ps wird einer zunehmenden Lokalisierung der Exzitonen und damit einhergehender Änderung der Kopplung an ihre lokale Umgebung zugeschrieben. Die Exzitonenpopulation zerfällt nach der optischen Anregung auf einer Zeitskala von über 100 ps und zeigt dabei ein nicht-exponentielles Verhalten. Die Rekombination an der Molekül/Substrat-Grenzschicht stellt den dominanten Zerfallskanal dar.

Der zweite Teil dieser Arbeit befasst sich mit dem Einfluss von Goldnanostrukturen auf die Elektronendynamik an der Ge(0 0 1)-Oberfläche. Selbst bei nominellen Goldbedeckungen von mehreren Monolagen bleiben die charakteristischen Germaniumoberflächenzustände erhalten. Die Populations- und Zerfallsraten der Germaniumzustände erhöhen sich jedoch deutlich. Dies wird dem großen Streuquerschnitt der Goldatome für angeregte Ladungsträger zugeschrieben. Weiterhin induziert die Adsorption von Gold die Bildung von eindimensionalen Nanodrähten auf der Ge(0 0 1)-Oberfläche. In Photoemissionsmessungen zeigen die Nanodrähte parabelförmige Elektronenbänder symmetrisch zum Gamma-Punkt bei k_{||} = 0,2Å^{−1} [4]. Durch Messungen mit einer Photonenenergie von 6,23 eV können die Elektronenbänder in direkter Photoemission durch Differenzmessungen von Au/Ge(0 0 1)- und Ge(0 0 1)-Proben sichtbar gemacht werden. Die Elektronenbänder zeigen die aus der Literatur bekannten Eigenschaften [5]. Da n- und p-dotierte Proben ähnliche Signale aufweisen, müssen die durch das Gold induzierten Zustände die Fermi-Energie 130 meV über dem Valenzbandmaximum pinnen. Die Untersuchung der Ladungsträgerdynamik in diesen Elektronenbändern zeigt unterschiedliche Elektron- und Lochlebensdauern: Im Vergleich zu Messungen bei 300K haben Löcher bei 160K nahe der Fermi-Energie eine deutlich höhere Lebensdauer als Elektronen. Dies beweist den eindimensionalen Charakter des Elektronensystems auf dieser Oberfläche [6].

This thesis deals with the development of an organocatalytic [3,3]-sigmatropic rearrangement of divinylcyclopropanes to cycloheptadienes. The reactive motif was formed in situ by condensation of α,β-unsaturated aldehydes with secondary amines.

After optimisation of the reaction, a variety of cycloheptadienes with diverse substituents was obtained in high yields and with excellent diastereoselectivities. Furthermore, the reaction was demonstrated to be stereospecific and proceeded under mild conditions. Hereby, the synthesis of a broad substrate library posed a formidable challenge. A synthetic strategy was devised in which the key transformation was the late-stage introduction of diversity in the final step by C–C cross coupling followed by one-pot deprotection. This strategy allowed most substrates to be derived from one common precursor. Individual substrates could be obtained by nickel catalysed reductive cross-coupling in a step efficient manner.

Intermediates of the substrate synthesis were applied to the selective modification of proteinogenic lysine residues.

This dissertation consists of three essays that investigate the effects and transmission mechanisms of monetary policy to the macroeconomy, and the role of financial frictions in modeling the business cycle. The first essay focuses on the question of how to include financial sector dynamics into macroeconomic models in order to improve their efficacy for macroeconomic policy analysis. We augment a standard New Keynesian model with a financial accelerator mechanism and show that financial frictions generate large state-dependent amplification effects. We fit the model to US data and show that the nonlinear model produces much stronger propagation of shocks than the linear model, particularly when shocks drive the model far away from the steady state. We document that these amplification effects are due to endogenous variation in financial conditions and not due to other nonlinearities in the model. Motivated by these findings, we propose a regime-switching DSGE framework where financial frictions endogenously fluctuate between moderate (low risk) and severe (high risk) depending on the state of the economy. This framework allows for efficient estimation with many state variables and improves fit with respect to the linear model. The second essay focuses on the following question: does monetary policy effectiveness in influencing the economy depend on households' balance sheets in the US economy? We investigate the interrelation between household balance sheets, collateral constraints, and monetary policy. We estimate a monetary DSGE model with financial frictions and occasionally binding borrowing constraints. The model implies stronger effects of monetary policy interventions when the borrowing constraint is binding compared to situations when it turns slack. In a prediction analysis we find that, out of a set of alternative plausible endogenous model variables, the level of household net worth is the single best predictor of the tightness of the borrowing constraint, which implies that monetary policy is more effective when household net worth is low. We test this model prediction in the data and provide robust empirical evidence on asymmetric effects of monetary policy across the household net worth cycle that validates the model predictions. A contractionary monetary policy shock leads to a large and significant fall in economic activity during periods of low household net worth. By contrast, monetary policy shocks have only small and mostly insignificant effects when net worth is high. The third essay focuses on the following question: how do credit constraints affect households' consumption response to monetary policy in the US economy? Combining detailed survey data on household portfolios, loan rejections, and consumption, I estimate the consumption response to exogenous changes in interest rates at the household level. I find large and statistically significant heterogeneity in the consumption responses across households, with constrained households being significantly less responsive. Specifically, the consumption response of unconstrained households to a monetary policy shock is between two to three times larger than the average response across all households. Using a New Keynesian model with heterogeneous households, I argue that this empirical finding is consistent with a model where financially constrained households have a low direct sensitivity to interest rates and indirect effects of monetary policy take time to materialize.

This thesis seeks to understand the repercussions of increasing ecological constraints and of the imperative of “greening” for the future of global capitalism. It engages in depth with the Green Economy (or green growth) approach developed by major international institutions (OECD, World Bank and UNEP) and focuses on the centrality, conditions, feasibility and by-effects of systemic accumulation in a green-capitalist economy. To theorize these, a conceptual framework is developed that distinguishes between political-economic and structural-economic constraints and comprises a set of functional and normative criteria for “green” capitalism (economic, ecological and social), potentially available “green” systemic accumulation strategies and empirically observable green-capitalist macro-strategies. This framework draws on a wide range of critical theory, including Marxian economics, regulation theory, world-systems analysis, Jason W. Moore’s world-ecology approach and further writings in political ecology.

It is found that a combination of political-economic and structural-economic constraints renders the market-oriented Green Economy approach largely ineffectual with respect to its declared intentions. Its non-confrontational politics are too passive even to realize a minimal “passive revolution” in the Gramscian sense. Instead, the “actually emerging” Green Economy assumes the form of an Economy of Additionality that leaves the fossil-fueled infrastructure of global capitalism in place and develops little transformative power. Prevalent “green” strategies partially internalize socio-ecological costs only to re-externalize these to vulnerable populations and ecosystems, in violation of the Green Economy’s normative standards and “win-win-win” promise.

Generally, most “greening” measures do not contribute positively to systemic accumulation but merely attempt, by rationalizing the maintenance of capital’s conditions of (re)production, to reduce the drag on accumulation exerted by ecological degradation and resource depletion. Against this background, the pressure for a “green-tech revolution” to resolve the fundamental capital—ecology contradiction is enormous, but the unprecedented absolute decoupling of systemic accumulation from environmental consumption remains physically and politically extremely unlikely, and “green” capitalism’s dependence on its realization is a very risky wager. These structural constraints equally apply to more politically balanced alternative green-capitalist projects such as neo-Keynesian proposals for a Green New Deal, suggesting systemic limits to the “greening” of capitalism. The hypothetical full internalization of socio-ecological costs, while not precisely quantifiable, might well render further systemic accumulation impossible by pushing down profit rates. Global capitalism is approaching planetary limits, the potential for the appropriation of “cheap nature” is increasingly exhausted – and “win-win-win” scenarios for nature, society and capital are not on the horizon.

Group B Streptococcus (GBS) is a major neonatal pathogen and a leading cause of infant mortality worldwide. Management of GBS infection relies on the prophylactic and therapeutic use of antibiotics. This approach has limited efficiency and increases antibiotic resistance. Carbohydrate conjugate vaccines are consensually regarded as the best possible alternative and several formulations have been and are now in clinical trials. In general, carbohydrate vaccine development suffers from shortfalls associated with the availability oligosaccharide libraries. Chemically pure glycans enable the prosecution of structure-immunogenicity studies that elucidate minimal epitopes and the intermolecular interactions responsible for recognition and immunity. One of the most promising methodologys to produce libraries of glycans is Automated Glycan Assembly (AGA). In this work, glycans from GBS are produced by AGA using the commercial synthesizer Glyconeer. The entire process is optimized since the production of building blocks to the automated oligosaccharide synthesis process. Ready-to-use building blocks (BBs) are required in bulk to do automated experiments in a continuous way. The synthesis of BBs can be achieved with a variety of different methods and the choice is usually based on the chemist preference and experience. This work optimizes and streamlines the strategies for the synthesis of building blocks for AGA bearing a thiolate aglycon as a leaving group. The synthetic schemes are completed and upscaled with minimal column purifications. This thesis goes on to describing the optimization of elongation cycles that introduce each BB in the growing oligosaccharide chain during AGA. The first target is GBS type IV capsular polysaccharide. In the synthesis of GBS type IV, the major bottleneck was the assembly of the Glc-α-1,4-Gal cis linkage. A trisaccharide containing this linkage was successfully synthesized. However, the low yields obtained rendered the elongation of the chain unsuccessful. The other target structures were related with GBS type III. With only three different BBs, four different GBS type III fragments were assembled. A sialic acid moiety present in the native polysaccharide was introduced enzymatically, proving that the combination of enzymatic sialylation with AGA is an expeditious approach to the preparation of complex glycans for vaccine development. Overall, the work in this thesis is a contribution to the standardization of the chemical work involved in AGA and a steppingstone for the fast and cheap production of GBS related glycans.

Implant-associated infections are devastating complications. The implant surface is very easy to be colonized by bacteria, which then form a biofilm. The biofilm on the implant surface is difficult to eradicate. Therefore, the prevention procedures for an implant surface are of crucial importance. Prevention of the implants begins with knowledge of the factors that cause the risk of infection, which can lead to the development of infection in different stages: preoperatively, intraoperatively, or postoperatively. The systemically injected antibiotic spreads through the entire body. As a result, the concentration, which arrives at the infection site is mainly sublethal. The insufficient dosage of such antimicrobials leads to unresolved infection because it often does not reach the infected site. Therefore, there is a critical need for a novel solution, either one, which allows the drug to reach the infection with high concentration and improve the biofilm penetration or the one, which helps the implant surface hinder bacteria colonization. In this PhD work few strategies for biofilm-based infections were introduced: prodrug antibiotic local delivery based on biorthogonal chemistry, antimicrobial coating against S.aureus utilizing the inverse-electron demand Diels-Alder reaction and MI-dPG polymer, antifungal impregnated PMMA bone cement against Candida spp. biofilms and electro-responsive hydrogels with photosensitizer curcumin release against MRSA.