This thesis proposes a novel approach for controlling and optimizing the optoelectronic properties of single-walled carbon nanotubes (SWCNTs) through functional groups for covalent functionalization and, ultimately, building photonic devices at the nanoscale. The carbon nanotube community demonstrated through decades of experiments the exceptional optoelectronic properties of SWCNTs. Semiconducting SWCNTs specifically have transitions that allow near infrared (NIR) fluorescence experiments for imaging purposes. To safeguard the fluorescence properties of the nanotube, Setaro et al. developed the first nondestructive covalent π-preserving functionalization (NCF) of SWCNTs using electron poor aromatic nitrenes (based on trichlorotriazine, called triazine in the following) via a [2+1] cycloaddition reaction in 2017. With additional spiropyran photoswitching groups, they could reversibly shift the Fermi level and facilitate charge transfer without introducing defect states that localize excitons, but preserving their diffusion along the tube. The functionalization approach required to replace the chlorine atoms of the grafted triazine already on the nanotube sidewall with molecular species (e.g. the spiropyran switch). The number of attached switches on the triazine could not be precisely controlled, making it challenging to obtain reproducibly a specific concentration of charges transferred between the nanotube and the organic molecule for optimal optoelectronic features. In this thesis, I worked on changing the synthetic approach of the molecular species attached on the SWCNTs in a fundamental way. Instead of attaching the targeted molecular species onto triazine on the SWCNTs, I developed a pre-functionalization strategy, in which I designed novel triazine derivatives with the desired chemical species replacing one or two chlorine atoms before grafting them onto the tubes. In this way, a successful grafting of the triazine onto the SWCNTs automatically ensures the presence and number of desired chemical species attached within the functional hybrids. I synthesized, characterized, and studied a defined set of charge transfer agents (CTAs) with a cyanuric chloride (triazine) backbone and varying substituents number and orientation that can withdraw or donate charges to the SWCNTs. The correlation between the optical properties and functionality of these CTAs was studied through experiments and simulations. Using the NCF approach, I covalently functionalized SWCNTs with these CTAs without destroying the sp2 crystalline network of the tube. Depending on the structural design of the CTAs, I observed the Fermi level position of the SWCNTs shift up or down by donating or withdrawing charges, as observed by Raman and XPS spectroscopy and confirmed by DFT predictions. As a result, the fluorescence intensity of the nanotubes is either quenched or enhanced, as evidenced by photoluminescence experiments. Effect of the reaction temperature used in the covalent functionalization strategy was also examined. Using only triazine molecule on SWCNTs, the impact of the functionalization temperature was found to directly influence the density of triazine molecules covalently attached to the SWCNTs, with 1 triazine molecule to 24 carbon atoms of the SWCNT at 150 oC and 1 triazine molecule to 155 carbon atoms of SWCNT at 25 oC. Across this temperature range, Raman studies at 638 nm laser pump show no increase of defectivity in the nanotube’s sp2 π network, as indicated by ID/IG ratios, while safeguarding the emission of different nanotube species in the photoluminescence spectra. The last part of this thesis builds upon the same pre-functionalization strategy and involves the stepwise synthesis of a novel photoactive triazine-spiropyran molecular complex, (1'-(4,6-dichloro-1,3,5-triazin-2-yl)-3',3'-dimethyl-6-nitrospiro[chromene-2,2'-indoline]), by attaching electron poor triazine to the nitrogen position of indoline moiety. Single crystal XRD and other spectroscopic analysis confirm the successful synthesis of triazine-spiropyran complex. UV absorption experiments show that triazine substituent strongly impacts the optical response of the complex during isomerization. Protonation followed by UV irradiation resulted in decreased absorptivity and appearance of a new absorption band at 390 nm. Subsequently, I covalently functionalized the triazine-spiropyran complex onto the SWCNTs, with Raman ID/IG ratios (measured using a 638 nm laser pump) indicating the preservation of the nanotube’s sp2 π-conjugated network. Activation of the triazine-spiropyran functionalized SWCNTs using UV photons induces reversible change in the nanotube’s EF, leading to ~52 % emission quenching, which is reversed upon thermal activation.

Cancer is among the leading diseases and causes for deaths worldwide. Even with a rise of treatment options in the last century, cancer therapy can still be limited and insufficient due to side-effects and drug resistances. Therefore, novel approaches have to be explored to overcome these limitations. In recent years, the development and application of antibody-drug conjugates, a combination of a highly cytotoxic payload with a target specific monoclonal antibody, have been receiving increasing attention. The majority of employed payloads in these antibody-drug conjugates can be considered as natural products or derivatives of these. Natural products make an important source for the development of novel anti-cancer drugs. Recently, microcystins, cyanobacterial cyclic heptapeptides, have been discussed as leads for the development of anti-cancer drug substances. Microcystins exhibit a high target toxicity by inhibiting eukaryotic serine/threonine protein phosphatases 1 and 2A. Unlike many cytotoxins that can cross cell membranes by passive diffusion, they depend on active uptake via organic anion transporting polypeptides 1B1 or 1B3, which are especially expressed by liver cells. This leads to a hepatotoxicity of microcystins and might limit the direct use of natural occuring microcystins as payloads. The aim of this thesis was to find optimized microcystins for use as payloads in antibodydrug conjugates. To maximize effectivity in targeted cells while reducing side-effects through uncontrolled uptake, these derivatives should display a high protein phosphatase inhibition potential but an overall low uptake by their transporters. As both phosphatase inhibition and transportability strongly depend on the structure of the individual microcystin, so-called clickable microcystins were modified with chemically diverse small molecules using click chemistry and tested for their bioactivity. A workflow for synthesis of new microcystins derivatives, structural confirmation, isolation, and quantification was developed. Two different kinds of click reactions, coppercatalyzed and strain-promoted, were used for synthesis. Different chromatographic approaches were chosen depending on the chromatographic issue, including solid-phase extraction, preparative, semi preparative, and analytical HPLC. Also, different detection methods depending on the analytical problem were used, e.g., mass spectrometry and tandem mass spectrometry for structural confirmation and an evaporative light-scattering detector for structure-independent quantification. 46 new microcystin derivatives were obtained and characterized through this workflow. In a second step, the influence of the small molecules on the bioactivity profile of microcystins was evaluated: an already established cytotoxicity assay was used to test for transportability, and a protein phosphatase 1 inhibition assay was established to test for target toxicity. The inhibition assay was complemented by a pharmacophore modeling approach. The results revealed that target inhibition and transportability of microcystins can independently be influenced by the physicochemical properties especially of the residue located in position 2 of the microcystin. The selectivity of the two transporters was evaluated to understand similarities and differences in substrates. Moreover, a ratio of transportability over inhibition potential was calculated to find optimized microcystins with high target toxicity but overall low transportability. It was shown that derivatization with small carboxylic acids or amino acids resulted in microcystins with a favorable ratio of inhibition to transportability, making these derivatives potentially suitable for application as payloads in antibody-drug conjugates.

Bei der Alzheimer-Krankheit handelt es sich um eine nicht aufzuhaltende, stetig fortschreitende neurodegenerative Erkrankung, deren frühzeitige Diagnose entscheidend für den weiteren Krankheitsverlauf ist. Aktuell angewandte, Liquor-basierte Biomarker sind zwar etabliert, weisen jedoch mitunter Limitationen hinsichtlich Frühdiagnose und Invasivität auf. Diese Arbeit widmet sich daher der systematischen Glykoanalytik von Liquor und Serum mit dem Ziel, Glykan-basierte Biomarker für die Frühdiagnose der Alzheimer-Krankheit zu identifizieren.

Ein neu entwickeltes Protokoll ermöglichte erstmals eine vollständige Analyse des Liquorglykoms hinsichtlich der darin vorkommenden freien, N- und O-Glykane mittels MALDI-TOF-Massenspektrometrie. Im Rahmen eines Screenings von 262 Liquorproben zeigten sich signifikante Unterschiede hinsichtlich spezifischer Glykanstrukturen zwischen Alzheimer-Patient:innen und Kontrollpatient:innen. Parallel dazu wurde eine innovative, datenunabhängige Massenspektrometrie-Technik zur Analyse von Glykopeptiden in 90 Liquorproben ohne deren vorherige Anreicherung angewandt. Aus über 11.000 generierten Peptiden konnten 498 Proteine, darunter 274 Glykoproteine, identifiziert werden. Dabei handelte es sich unter anderem auch um zahlreiche mit der Alzheimer-Krankheit assoziierte Proteine mit auffälligen Glykosylierungsmustern.

Zusätzlich dazu wurde ein robustes und reproduzierbares Analyseprotokoll für die Detektion von Glykosaminoglykanen mittels MALDI-TOF-MS entwickelt. Dieses soll nachfolgend ebenfalls bei der Entwicklung eines Glykan-basierten Biomarkers für die Frühdiagnose der Alzheimer-Krankheit angewendet werden. Durchgeführte Vorversuche zeigten vielversprechende Ergebnisse hinsichtlich der Unterscheidung von Alzheimer-Patient:innen und Kontrollpatient:innen.

Die Ergebnisse dieser Arbeit bilden die Grundlage für die Entwicklung neuartiger, Glykan-basierter Biomarker für die Frühdiagnose der Alzheimer-Krankheit.

Organoboron compounds play a central role in the chemical sciences. The classical approach to access this class of molecules entails incorporation of the boron motif in an advanced intermediate and has been implemented in a variety of different transforms, from the venerable Brown hydroboration to innovative platforms like C─H borylation. Alternatively, a core scaffold already containing a boron moiety can be subjected to further functionalization. In order to avoid side reactions at the boron center, protecting groups are generally employed. This has the drawback of adding additional steps to the synthetic sequence. The resulting inefficiency can be overcome by relying on methodologies capable of selectively manipulating multifunctional units that contain and retain an unprotected boron handle. This thesis describes the development of transforms of this latter kind. By relying on either photochemistry or transition metal catalysis, the expedient conversion of multifunctional boron reagents into complex 2D and 3D organoboron compounds could be achieved. Chapter 2 details the development of a method that generates α-boryl radicals from α-iodo boronic acid pinacol esters without the need for catalysts. Interception of the generated open shell species with styrenes afforded E-allylic boronic esters. The mild conditions of the protocol, which requires only a simple Lewis base additive and visible light, showed broad functional group tolerance and allowed its strategic alignment with energy transfer catalysis to access the Z-stereoisomers of the products. Chapter 3 describes the expansion of this chemoselective activation platform to a trifunctional reagent, featuring an additional nucleophilic handle (Si, Ge or B based). C─I bond homolysis yielded an α-bimetalloid radical of increased electrophilicity. Thanks to this, a wider array of SOMOphiles could be engaged, producing valuable 3D borylated scaffolds. These, in turn, could unlock a vast portion of chemical space via the chemoselective manipulation of the two installed nucleophilic moieties. Finally, the mechanism was interrogated via in depth experimental and computational investigations. Chapter 4 describes the development of a transition metal catalysed method for the synthesis of complex 2D organoboron scaffolds. A regioselective Suzuki-Miyaura cross coupling/cyclization reaction between readily available vicinal diborylated alkenes and 2- halophenols allowed the synthesis of 3-substituted benz(oxa/aza)borines, heterocycles that have been receiving increasing attention from medicinal chemists. The modular nature of the protocol provided rapid access to a Xeruborbactam derivative and its functional group tolerance allowed incorporation of multiple synthetic handles. These were exploited in downstream chemoselective manipulations and to install biomolecular probes.

Mass spectrometry-based proteomics allows to take a snapshot of the state of cells on the protein level. In particular, it allows to study the entire proteome in a high-throughput manner with high sensitivity. It is furthermore able to provide insights into peptidoforms, which are peptides that have sequence variations or are post-translationally modified. These play a major role in cell signaling and gene regulation, but can also be linked to certain disorders. So, studying peptidoforms and proteoforms provides fine-grained phenotypic insights that are of high biological relevance. However, the identification of peptidoforms, using mass spectrometry-based proteomics, is challenging from at least two directions. First, the underlying tandem mass spectra contain additional, rare, and potentially hard-to-simulate patterns. Furthermore, contextual knowledge in the form of reference proteomes, which initially contain canonical reference proteins, cannot be extended indefinitely to account for all potential peptidoforms. This is because considering all possible combinations of modifications and sequence variations is not tractable due to combinatorial complexity. Hence, this thesis provides new deep learning methods that improve the identification of peptidoforms in mass spectrometry-based proteomics while being interpretable. First, I introduce AHLF as a new end-to-end trained deep learning model that predicts modified peptides based on their fragmentation tandem mass spectrum (MS/MS) spectra. I am able to show that AHLF’s prediction score boosts peptide identification rates in the context of phosphoproteomics and for cross-linked peptides. AHLF is a temporal convolutional neural network temporal convolutional neural network (TCN), which I trained on 19.2 million of historical peptide-to-spectrum matches. For interpreting AHLF, I estimate feature importances per peak and per spectrum. These peak-level importances show that AHLF is indeed focusing on peptide-specific fragment ions. Additionally, I investigate the prediction performance across varying quality of data, denoting that variation occurs due to instrument type, resolution and dissociation method. In the second part of this work, I present yHydra which is a foundation model that I trained on nearly 20 million peptides and MS/MS spectra. I designed yHydra as a foundation model to be able to implement various downstream sub-tasks. In particular, I demonstrate that yHydra is able to perform closed, open, and error-tolerant searching. Using yHydra, I demonstrate error-tolerant searching of antibody peptide sequences searching and in the context of cross-species searching of chimpanzee plasma samples. Lastly, I demonstrate the of explainability yHydra by visualizing the learned joint embedding of peptides and spectra which reveals a learned manifold that is structured in concordance of physico-chemical properties of embedded peptides.

Unpaired adatom spins on superconductors interact with the Cooper pairs of the substrate and induce Yu-Shiba-Rusinov (YSR) states inside the excitation gap. Using combined scanning tunneling microscopy and spectroscopy (STM/STS) methods, we can probe these states at the single-atom scale. Additionally, adatoms can be moved on surfaces with atomic precision by lateral manipulation using the STM tip. If the YSR wave functions of two impurities overlap, they may hybridize forming a symmetric and an antisymmetric linear combination of the monomer wave functions similar to the linear combination of atomic orbitals when forming molecules. In structures consisting of many magnetic adatoms YSR bands can develop and, for specific parameter ranges, realize topological superconductivity.

We investigate structures of Fe and Mn atoms on the quasi-two dimensional superconductor 2H-NbSe2. We start out by studying symmetry properties of hybridized YSR states. Because the symmetries of YSR wave functions are determined by the crystal field of the corresponding adsorption site of the magnetic atoms as well as the Fermi surface of the substrate, we can employ the symmetries imposed by the substrate to realize chiral, triatomic YSR molecules which cannot be obtained in gas-phase chemistry. Interestingly, we also observe an odd parity ground state in dimers without a mirror plane between both atoms. This ground state makes the dimer a promising start for a chain that may host topological superconductivity. We extend the dimer to a linear chain of 24 atoms and observe the formation of YSR bands. In long chains the YSR bands are influenced by the incommensurate charge-density wave (CDW) that coexists with superconductivity in NbSe2.

Just as YSR bands in chains, the YSR states of individual Fe atoms on NbSe2 are influenced by the CDW. Here, we demonstrate that Fe atoms also influence the CDW. We reversibly switch the CDW-to-lattice alignment around Fe dimers by manipulating additional Fe atoms at a distance of more than 6nm from the dimers and observe significant changes in the YSR states of the dimers upon switching the CDW. Finally, we explore Mn atoms on 2H-NbSe2. We find that the YSR states of individual Mn atoms are less influenced by the CDW than those of Fe atoms. While we do not observe hybridization of YSR states in Mn dimers, we find signatures of spin excitations in chains of densely spaced Mn atoms.

Reconstructing the carbonate chemistry of the past ocean is a central goal of paleoceanography. In this regard, the boron isotope composition of marine carbonates has become a promising and widely used proxy for the pH of ancient seawater. However, a major concern in the application of this proxy is that the isotopic composition of carbonates may have also been influenced by secular changes in the isotope value of seawater (δ11Bsw). The purpose of the present thesis is to address this potential source of bias and investigate the likely changes in δ11Bsw from the Cretaceous to the present.

We do this by first experimentally examining boron adsorption on clay minerals, one of the key mechanisms by which boron isotopes are fractionated in the ocean. Cleaned samples of kaolinite, smectite and illite were suspended for 48 hours in a fixed volume of fluid (with a solid-to-fluid mass ratio of 0.04), containing boron at a known concentration and isotopic composition. The ability of each clay mineral to sorb and isotopically fractionate dissolved boron was determined by measuring the boron content of the fluid before and after interaction with the clay minerals. This basic experimental procedure was repeated multiple times under varying levels of pH, ionic strength, dissolved inorganic carbon (DIC) and major ion concentrations to probe the sensitivity of boron adsorption to fluid chemistry.

When clays are suspended in a pure aqueous boron solution without any other dissolved constituents, boron adsorption is inefficient and approximately constant over a wide range of pH. This is because clay edge surfaces, where most adsorption takes place, remain neutral regardless of the acidity of the surrounding fluid, inhibiting complexation of either B(OH)3 or B(OH)4-. In contrast, clay edges can become charged if the ionic strength of the surrounding fluid is high. Complexation reactions of boron in seawater are therefore strongly dependent on pH, as the pH sets both charge state of clay minerals (positive, neutral, negative) and the speciation of boron (B(OH)3 or B(OH)4-). We identify maximum rates of boron adsorption for all clay minerals in alkaline seawater. At these conditions, adsorbed concentrations of boron can be between six to twelve times higher than those of dissolved boron in the surrounding fluid. Isotope fractionation associated with adsorption is maximized at a pH of 8 (approximately 20 ‰ between fluid and clay) but becomes negligible at very alkaline or acidic conditions (~ 0 ‰). Complexation modeling shows that the isotopic composition of adsorbed boron is consistent with a high affinity of B(OH)4- to the clay surface, in agreement with previously published experimental work. As a result, detrital clay minerals isotopically fractionate seawater by preferentially adsorbing isotopically light B(OH)4-, not because the adsorption process itself induces a specific isotopic fractionation of adsorbed boron.

Moreover, our results demonstrate that adsorption behavior of clay minerals is not clearly altered when adsorption occurs in seawater with a major ionic composition close to that of the Eocene or Cretaceous oceans. Long-term changes in seawater chemistry consequently had little impact on the boron adsorption flux, which was instead set over time by the total mass of sediment entering the ocean as well as its mineral assemblage. To further explore the impact of these parameters on the boron adsorption sink, we model a number of plausible erosion scenarios and the associated sediment discharge for the last 100 million years. The model takes into account changes in terrestrial climate and erosion patterns to predicts the abundances of five boron-adsorbing minerals (kaolinite, chlorite, illite, smectite and iron oxyhydroxides) in the global sedimentary discharge. Our results show that changes in the terrestrial climate had a limited impact on the global-scale abundance of these minerals because a warmer and wetter climate state in the past was balanced by a reduced land mass in tropical latitudes. On the other hand, changes in sediment provenance could have significantly altered the mineral assemblage. Previous studies suggested a lack of mountainous erosion in the Cretaceous and early Paleogene which, according to our erosion model, caused discharged sediment at these times to be composed of 40 % clay minerals (compared to 15 % today). In other words, the large acceleration in sediment discharge thought to occur over the course of the last 40 million years was dominantly comprised of minerals with a small specific surface area that do not adsorb boron in significant quantities. Our results therefore show that the capacity of detrital sediments to adsorb boron from seawater has remained similar to today for most of the Cenozoic.

We finally combine these findings on the boron adsorption sink with additional advancements made for other relevant parts of the Earth system to construct a new model for the evolution of δ11Bsw. Critically, our model also includes a self-consistent representation of the lithium isotope value of seawater (δ7Lisw), as both lithium and boron are mechanistically coupled because of their shared dependence on the same geologic processes. These processes include the riverine discharge of water and sediments, precipitation of carbonate and silica in the ocean, marine productivity, early sediment diagenesis and exchange reactions between seawater and the ocean crust. The model allows us to simulate the effect of proposed changes in various lithium and boron fluxes, and test their ability to match available seawater reconstructions. We find that seawater proxy data of both boron and lithium can be explained by a hitherto unrecognized long-term rise in the pH of soil porewaters, which we attribute to aridification of the global land surface. During the Cretaceous and Paleogene, soils were acidic (pH < 7) so secondary minerals forming in soils reincorporate only small amounts of solubilized lithium and boron with a modest isotope fractionation. Rivers at this time consequently delivered large amounts of isotopically light boron and lithium to the ocean. The model produces minimum δ11Bsw values of 36 and 37 ‰ for the late Cretaceous (85 Ma) and early Eocene (50 Ma), respectively. As the planet cooled and land surfaces dried in the latter half of the Cenozoic, soils became more alkaline (pH > 7) and the propensity of soil minerals to reincorporate and isotopically fractionate solubilized boron and lithium increased. This caused the river input and, accordingly, seawater compositions of both elements to become isotopically heavier over time. The δ11Bsw increased at a steady rate of 0.06 ‰ per million years from the early Eocene to the present and did not exceed its modern value of 39.6 ‰ at any time over the last 100 million years.

Turbulence is an important feature of blood flow near the heart. A discretization of moderate resolution must therefore model the interactions between "coarse" resolvable flow behaviors and "fine" subgrid-scale features. We compare several choices of turbulence model in terms of their impact on clinically interesting flow statistics. We also present an investigation of a novel method for augmenting classical turbulence models with machine learning algorithms trained on coarse-fine simulation pairs.

Die empirische Studie untersucht, ob durch historische Auseinandersetzung die Herausbildung europäischer Identität bei Kindern am Ende der Grundschulzeit beeinflusst wird. Dazu wurden Leitfadeninterviews mit Grundschüler*innen (n=19) im Alter von ungefähr zehn Jahren durchgeführt, die anschließend mittels Qualitativer Inhaltsanalyse ausgewertet wurden. Die Ergebnisse zeigen, dass Kinder am Ende der Grundschulzeit über vielfältiges Wissen und unterschiedliche Konzepte zu Europa verfügen, deren Qualität variiert. Dieses Wissen bezieht sich auch auf europäische Vergangenheit und es kann gezeigt werden, dass Kinder über umfangreiche Kompetenzen des historischen Denkens verfügen, die sie befähigen, Europa in historischer Perspektive zu betrachten, was sie auch tun. Besonders häufig formulieren die Kinder die Narration, dass sich Länder zu Europa zusammengeschlossen haben um Kriege zu beenden und Frieden zu schaffen. Die Aneignung von Wissen und historisches Lernen findet dabei hauptsächlich außerschulisch statt. Durch die geschichtliche Auseinandersetzung mit Europa verstärkt sich ein europäisches Bewusstsein der Kinder. Das europäische Bewusstsein ist unterschiedlich stark ausgeprägt. Aufbauend auf diesem Bewusstsein kann eine europäische Identität bei Kindern am Ende der Grundschulzeit als in der Entwicklung beschrieben werden.

Das deutsche 19. Jahrhundert stand im Zeichen von intensiven Bestrebungen der Nations- und Nationalstaatsbildung. Ihre mit der historisch verankerten föderativen Tradition verbundenen Herausforderungen führten zum Einsatz emotional geprägter Bewältigungsmittel sowohl zur Kristallisierung einer als einheitlich imaginierten Nation als auch zur inneren Konsolidierung des Kaiserreichs von 1871. Darunter ragten seit dem Humanismus im deutschen Nationsdiskurs fest eingebettete und deshalb re-applizierungsfähige sowie auch durch moderne Deutungseliten neukreierte Mythen hervor. Ihre Bedeutung für die Stiftung von Identität, beruhend auf Konstituenten des deutschen Nationalcharakters wie Ethnos, Sprache, Geschichte, Religion, Recht u. a. stand den politischen und militärischen Vorgängen in nichts nach. Mythen halfen Welt- und Geschichtsbilder zu konstruieren, wirkten aktiv bei der Grundlegung eines kollektiven Gedächtnisses mit und trugen zugleich zur wesentlichen Überexponierung des deutschen Volkes als Träger der Nation und deren Staates bei. Zur Avantgarde nationaler Mythenproduktion und -popularisierung gehörte der Juraprofessor und Erfolgsautor Felix Dahn. Mit seinem umfangreichen wissenschaftlichen, vor allem aber literarischen Werk genoss er enormes Ansehen nicht nur bei der deutschen Leserschaft. Dieses stützte sich nicht so sehr auf die ästhetischen Qualitäten seiner Schriften, sondern in erster Linie auf die Symbiose zwischen der Fundierung historischer Kontinuität und der Heraufbeschwörung von Glanz, aber auch von Untergang verheißender äußerer und innerer Bedrohung des germanisch-deutschen Volkstums in seinen ethnischen Merkmalen und Facetten sowie dessen Staatsgebildes. Markante Topoi bilden dabei die gefährdete deutsche Sprache, die Diskrepanz zwischen nationaler Eigenart und „wesensfremden“ Glaubens- und Rechtsformen mit deren Konsequenzen für die Bewährung des Wilhelminischen Reiches und dessen kulturellen Daseins, die Lebensraumerweiterung und die als Krönung des Kriegers stilisierte Ethik des Heldentums in ihrer Funktion, Garant der Volks- respektive der Staatsexistenz zu sein. Vor diesem Hintergrund setzt sich die Studie mit dem Beitrag Dahns zur Etablierung des mythengestützten Nationalismus im ersten deutschen Nationalstaat zwischen 1871 und 1914 auseinander. Die Erschließung der Semantik und der Wirkungssphären seiner mythischen Schöpfungen versteht sie als semiotische Ermittlung von für Dahns Identitätsstiftungsstrategie konstitutiven Vorstellungen, deren Objekte zeichenartige Sinnträger verschiedenen Ranges (Symbole, Mythen) darstellen. Pragmatisch fasst die Semiotik das Zeichen als eine bilaterale Einheit von Bezeichnendem und Bezeichnetem auf. Sie besteht aus der spezifisch materialisierten Form des „Ausdrucks“ und einem bedeutungstragenden „Inhalt“. In semiotischem Sinne weisen Symbole und Mythen dieselbe dualistische Struktur auf. Deshalb eignet sich das Zeichenmodell als Grundlage ihrer theoretischen Erfassung. Den Mythos als spezifische Textsorte charakterisiert vor allem sein symbolischer Kern. Die Narrativität verbindet das mythische Symbolgebilde genealogisch mit dem hier literarischen Medium seiner Exponierung. Im Unterschied zum Symbol präsentiert der Mythos sein Ideengut nicht piktografisch konzentriert, sondern in der Form fabulierter Erzählung mit ausgeprägtem Zeit-Raum-Kontinuum, welche eine doppelschichtige Struktur erkennen lässt. Die in verschiedenen Episoden unter der Beteiligung agierender Figuren in bestimmter Reihenfolge verlaufende Handlung bildet die Oberflächenstruktur. Für die Semantisierung von Merkmalen (Mythemen) der untereinander kooperierenden oder rivalisierenden Aktanten ist die Tiefenstruktur maßgeblich, auf deren Ebene die handelnden Gestalten als Protagonisten bzw. Antagonisten auftreten. Trotz verschiedener Verflechtungen der mythischen Narrationen im Kaiserreich ist eher von diskursiv koexistierenden Mythen als von einer Mythologie im klassischen Sinne zu sprechen. Es werden in Mythologemen gebündelte Mythenstränge zusammengelegt. Als Mythologem bezeichnet diese Untersuchung von Dahns Mythen ein, auf der wiederkehrenden Aufeinanderbeziehung emblematischer Symbole und Mytheme beruhendes Organisationsprinzip, das Mythensysteme mit symbolsemantisch konstruierten Gefügen benennen lässt. In genremäßig unterschiedlichen Texten gelang es Dahn, eine zu nationalistischen Erziehungszwecken einsetzbare mythische Konstruktion mit identitätsstiftender Semantik aufzubauen, deren tragende Elemente zwei Hauptstränge von aufeinander bezogenen fundierenden Mythen aufweisen. Ihre signifikante, mit dem Ethnischen verbundene Blut- respektive für das Kriegerische stehende Eisen-Komponenten beinhaltende Symbol- und Mythem-Substanz, welche anhand der Oberflächen- und Tiefenstrukturen von artifizierten Varianten des Germanenmythos sowie der Mythisierung zeitgeschichtlicher preußischer Personen und Ereignisse mithilfe semiotisch-strukturalistisch orientierter Analysestrategie expliziert wird, ermöglicht die Identifizierung eines diese Mythen zusammenfügenden Mythologems. Es verleiht jener in der Verkettung des germanisch-deutschen Geschichts- und Identitätsbewusstseins mit der heldenhaften Opferbereitschaft für Volk und Staat wurzelnden Mythenwelt des Nationalstaats einen Systemcharakter. Die fokussierte biographische Thematisierung sowie die Erörterung von Dahns philosophischer, politischer und ideologischer Anschauung dient der Orientierung hinsichtlich der schwierigen Einordnung seines Ideenguts und „Blut und Eisen“-Mythologems in das Ideologie-Spektrum des Kaiserreichs. Dahns führende Rolle als herausragender Exponent der Mythisierung des Nationalen für die konstruktivistische Erfindung von nationalen Imaginationen und Identitätsmustern, aber auch sein Engagement bei ihrer Propagierung werden an der intensiven und nachhaltigen zeitgenössischen Rezeption verifiziert. Die Kritik an dessen weitgehend dem Zeitgeist bzw. den Erwartungen des breiten Publikums entsprechenden Gesinnung, die ideologischen Vereinnahmungsversuche und die eigene Verwahrung dagegen deuten auf eine massive und anhaltende Wirkung des durch ihn elaborierten Mythologems hin. Die pointierte Topographierung der Kompatibilität und Divergenz seiner Ansichten mit den ideologischen Fundamenten der sich von den 1890er Jahren an formierenden, breitgefächerten völkischen Bewegung veranschaulicht es, dass der sich in Freikonservatismus transformierende Nationalliberalismus Dahns und sein Deutschtum ihn innerhalb des zwischen Patriotismus und völkischem Radikalismus oszillierenden wilhelminischen Nationalismusdiskurses im Bereich einer auf Sicherstellung des Volks- und Staatserhalts bedachten gemäßigteren nationalistischen Volkstumsideologie verankern ließen.

The thesis examines the management tools introduced by the Safavid shahs to alter the Shrine of Imam Reżā in Mashhad from a mere place of pilgrimage to a center for disseminating Shiʿi con- victions. It furthermore aims to create a deeper comprehension of the multiple functions of the Āstān-e Qods as a cultural, social and economic institution in the years 907/1501 to 1148/1735. It enhances the argument that the foundation for developing the Shrine in this manner was laid by Shah Ṭahmāsb I and that Shah ‘Abbās I increased both the significance and the financial means of the Shrine by undertaking several measures, such as constructing additional buildings, enlarging its architecture and embellishing the city of Mashhad and by establishing endowments and encouraging votive offerings to the Shrine. The main part of this study is based on a large number of unique original documents kept in the Āstān-e Qods, many of which are presented and analyzed here for the first time. The en- dowment deeds reveal the significant increase in the number of endowments in this period and give insight into the motivation of the donors in support of the religious policy of the Safavids, making this dynasty extremely successful in achieving their religious and political goals by the end of the period. We have, moreover, scrutinized the different types of orders issued by the Sa- favid shahs, highlighting the methods by which the shahs managed the Shrine directly, the main role of the ṣadr and his office, the dīvāno’ṣ-ṣedāre (Office of the ṣadr) and the important role of the dīvān-e a‘lā’ (Supreme Government Office) in this context. Subsequently we have focused on the tasks of the motavallīs (custodians) of the Shrine, described their position as deputies of the Shah and attempted to identify them. Another part of the study focuses on the organization of the Āstān-e Qods, predominantly the duties of the official with the title Sarkār Feyż Āsār (lit. “Department of Divine Grace”), and the formation of the secretariat and the daily shifts (kešīk) in the Shrine, which had increased from three to five in the early Safavid period. Besides the analysis of the chancellery documents kept in the Āstān-e Qods, the study also offers insight into the preparation of the record called ṭūmār-e nasaq (“fiscal management instruction scroll”) as a manual for managing the Shrine through the dīvān-e aʿlā’. The main aim is to show how the organization of the Āstān-e Qods functioned by analyzing the development of the Shrine and its endowments under the di- rect management of the Shah and the dīvān-e aʿlāʾ. It highlights the striking similarities between the official structure of the Shrine, as revealed in its administrative manual, and the highest Sa- favid government office. The documents reveal how the organization of the Shrine of Imam Reżā grew due to the establishment of endowments, whose revenue contributed to embellishing the Shrine and played a principal role in supporting the political objectives of the Safavids: rather than remaining only a place for pilgrimage, it became an institution for actively disseminating the Shiʿa by attracting a large number of pilgrims and Shiʿite scholars. This development led in turn to the emergence of other functions, increasing the central importance of the Shrine. The organization of the Āstān-e Qods Rażavī and its endowments expanded under the direct management of the Shah who appointed the Shrine’s motavallī. The Shrine’s fiscal matters and endowments were man- aged by the dīvāno’ṣ-ṣedāre via the central government office, the dīvān-e a‘lā’. The documents of the Safavid administrative system, which have survived in the Āstān-e Qods, are unique origi- nal copies of these financial operations, which clarify the relationship between the Safavid shahs and the motavallīs of the Shrine. They furthermore shed light on the functions of the other high government officials in the management of the Shrine. They show in detail, how the income of the Āstān-e Qods was used to strengthen the country's religious foundation and how its endow- ment policy aimed at expanding the reach of Shiʿite propaganda.

This research reconstructs the historical process of the formation of local political power and the state in the department of Chocó, Colombia. Throughout the text, the idea of the state as a homogeneous and aseptic entity is challenged, and it is rather understood in terms of its ambiguous and contradictory features in its practices, which even become "illegitimate". The first chapter seeks to understand the process of state formation and local power in the late nineteenth and early twentieth centuries. The configuration of local power in those years represented a tense interaction between the minority 'white' political power in the territory and the majority black and indigenous population, but with limited access to the state apparatus and its institutions. In the midst of this, a relationship with Bogotá was established that positioned the territory as peripheral and abandoned throughout the twentieth century. This chapter examines the role of roads and rivers as instruments of power over the territory, since they were and are spaces through which the daily lives of the Chocoan people passed and through which the state made its way in the process of configuration. This was the perception of the local and regional powers, who had a desire to control them and to establish a particular domination over the territory. However, this attempt at domination did not go smoothly and the fires, as an apparent response of resistance to white power, show the level of confrontation and dispute that took place in the territory. Despite these disputes, at the beginning of the 20th century these conflictive relations began to change as the local political power, in its claim for autonomy from the tutelage of Bogotá, began to recognise the black population as fundamental to the development of local political life and a "better" relationship with the Andean power. In addition, the extractive processes, which involved confrontations between large mining companies, black people (artisanal miners) and local powers, highlighted the use of state instruments by the population to defend the forests and acquire mining titles. These conflicts were part of the beginning of the rapprochement between local traders, who were part of the local power, and the black mining population, as both groups were building the extractive and commercial economy from which they also benefited. Although the two sectors had different relationships with the state, this interaction is in itself evidence of the inhomogeneous and contradictory character that characterised the state-building process of those years. The second chapter shows the process of reconfiguration of political power in the territory between 1920 and 1950. These were the years of the rise of black power in the territory. The process of state 231 formation in those years was linked to the type of governance that emerged in Chocó as a result of the processes linked to the mining circuit and the department's position as the border of the recently separated Panamanian territory. This allowed for a certain capacity to negotiate with the power in Bogotá. The local power demanded autonomy, and although they obtained some, it was limited and under the watchful eye of Bogotá. This showed the capacity of the state to be present in the territory and linked the local powers to the national project. The participation of black people in mining gradually opened the way for them within the state and political power, and made concrete their intention to be part of the institutional game of the state, and the channel used was the political parties. These were central to local government. The presence of the parties led to a significant politicisation of the territory, as evidenced by the frequent electoral disputes. Thus, while the parties played a central role in access to the state and the national project, blacks who had made their fortunes in mining, trade and agriculture gradually entered popularly elected and appointed bureaucratic positions. The presence of black people and the role of commerce were central to the constitution of the territory as a liberal majority. Because access to the state was mediated through the role of political parties, the territory, like the rest of the nation, was caught up in the dynamics of partisan violence. This violence was also a manifestation of Chocó's connection to national dynamics. Meanwhile, the Catholic Church sided with the conservatives in an attempt to whip up sentiment against the liberals. However, the church's limited roots in a predominantly black area meant that its impact was limited. The rise of black power also transformed the church in the area. These changes and manifestations showed a shift in power relations within the territory. The emergence of workerism and the promotion of public education led to the definitive rise of black power in the political scenarios of the territory, coinciding with the revaluation of the black and the Chocoano, in contrast to the stereotypes coming from outside the territory. However, the rise of this new power was not without contradictions. Ethnic tensions intersected with class tensions. The rise of the blacks did not mean a break with white demands for traditional political power; on the contrary, many of them were taken up. Despite the denunciations of the state's dysfunctionality, its legitimacy does not seem to have been lost, but rather continually sought. The arrival of blacks in positions of power coincided with the rise of socialist discourse, which generated a discussion of the black question in local power circles. Moreover, this rise was indicative of a transformation that was taking place in the territory, leading to the departmentalisation of the territory. 232 The third chapter discusses the role of local power in Chocó during La Violencia and the Rojas Pinilla dictatorship between 1948 and 1957, and how different forms of social mobilisation emerged in response to political repression. Half a century of violence had a moderate impact compared to the dynamics of the Andean world. The characteristics of Chocó's liberals and conservatives showed an "affinity" to statehood in the years of the recently won departmentalisation, which in part would have distanced the possibility of confrontation with the state, although the discourse of La Violencia was used as a channel of communication with the national. Likewise, the socio-economic structure of the Chocó, with the absence of a hacienda model and the dominance of the Liberal Party, whose local militancy had no one to confront. However, the expansion of the conflict from the borders with Antioquia showed how the territory was linked to national dynamics. The violence served as a channel for the emergence of new forms of governance, in which the state of siege provoked the retreat of the Liberal Party, which capitulated to Bogotá and submitted to the temporary power of the military. Meanwhile, the conservatives were unable to capitalise on their electoral power, despite their dominance of the local state administration, because the absence of elections limited their ability to build a bureaucracy that could guarantee their permanence in local political power. Despite the low level of violence in Chocó, its existence affected the territory's relationship with the central government. The liberals were temporarily excluded from local power and the autonomy mechanisms achieved through departmentalisation were not implemented, while the imposition of military mayors was a sign of state control based on violence. Local political power was able to make traditional demands for infrastructure and state presence in the early years of the Rojas dictatorship. The figure of the governor and the Comité de Acción Chocoana were the intermediaries for these demands. Beyond the dictatorship, local power was able to consolidate its hold on the territory. The military also consolidated local political and state power in the area by attempting to dismember the department. The lack of services and infrastructure provoked a constant demand from the state, and local power, through the parties, continued to become the intermediary of this demand. In this way, Chocó was more than just a marginal territory; it had an important articulation with the process of state formation during this period. The fourth chapter focuses on the local impact of the National Front and the decentralising reforms of the Colombian state and the emergence of the violence of the armed conflict. During this period, 233 the territories were put on an equal footing in terms of their articulation with the political system. It shows that local administrations were put on an equal footing in terms of local governance and the implementation of the new regime. These changes were preceded by the death of one of the most important political leaders in Chocó and the departure of the traditional white families and the former Syrian-Lebanese traders due to the fire in Quibdó. One of the effects of the new regime was to equalise the bureaucracy, despite the fact that Chocó was a predominantly liberal area. The state thus homogenised the territories without taking into account local electoral dynamics, and the population and political power do not seem to have rebelled against such a situation. The new regime brought with it the expansion of the state and the arrival of new resources in the territory. The aim was to rehabilitate areas affected by violence and to accelerate the growth of areas lagging behind in order to prevent the outbreak of new violence. As a result of this expansion, the central, departmental and municipal governments grew, along with a decentralised parastatal bloc and the expansion of the legislative and judicial branches. This expansion brought with it the creation of new offices and bureaucracies for the territory and meant a local struggle for its control during the National Front and later years. As a result, ideological labels and party affiliations were lost in the search for access to the bureaucracy. Politics in the Chocó was reduced to the administration of elections, and it became increasingly clear that the parties were preventing social change, with the result that the support of the Chocoanos for elections, which had always been the mechanism for legitimising the political and party system and one of the main channels for linking the population to the institutions of the state, was declining. As in the rest of the country, the Chocó saw an increase in social protests, mainly demanding the extension or implementation of public services. Despite these popular demonstrations and denunciations of the absence of the state and of corruption, the leftist parties did not achieve major electoral successes, but the demands did provoke a response from the state that led to the search for a broadening of the political system. 234 The reaction of the traditional parties to the possibility of a democratic opening triggered the intensification of violence, which began to escalate in the 1980s. The "opening", however, did not mean any significant changes for the parties, for the local authorities or for the improvement of the administration of the state at the local level. Despite the denunciations of bad administration, political power continued to be shared amidst the traditional disputes within the party, which did not undergo any unfavourable changes in the eighties in terms of the electoral aspect. The point of arrival is the emergence of the violent reaction of local power and the state to the attempt to open up the state itself. It is part of the beginning of the violence of the armed conflict in Chocó.

Borderline Personality Disorder (BPD) is a severe mental disorder characterized by a disturbed relational style, emotional dysregulation, and impulsive behaviors. Individuals with BPD often engage in aggressive or dismissive behaviors in relationships. These difficulties are driven by a pervasive fear of abandonment and a constant expectation of rejection. They are likely linked to deficits in social cognition, which is the accurate interpretation and response to social signals, including facial emotion recognition (FER), empathy, and prosocial behavior. Studies on social cognition in BPD yield inconsistent results ranging from impaired to enhanced capabilities. One promising factor that may account for heterogeneous results is stress. Stress, especially in social contexts like exclusion, exacerbates many BPD symptoms, contributing to interpersonal dysfunction and emotional instability. However, research on how stress affects social cognition in BPD is limited, and results are mixed. This dissertation aims to address this gap by examining the effects of social stress on social cognition in female patients with BPD, particularly on FER, empathy, and prosocial behavior. Given previous conflicting findings, the first specific aim of this dissertation is to examine whether FER in individuals with BPD remains intact under social stress. Moreover, previous research suggests that healthy individuals react to psychosocial stress with a prosocial reaction, including elevated empathy and prosocial behavior, which can be interpreted as a “tend-and-befriend” reaction to stress. Women with BPD, on the other hand, reacted to psychosocial stress with reduced emotional empathy, possibly suggesting an aggressive or less prosocial “fight-or-flight” reaction to psychosocial stress. The second aim of this dissertation is to explore whether social exclusion, a particularly stressful experience for individuals with BPD and a key component of psychosocial stress, might explain this reaction previously seen in women with BPD. Lastly, the role of testosterone, which has been linked to aggressive and competitive behaviors, will be examined, as its relationship with prosocial behavior after social exclusion in BPD remains understudied. These aims resulted in the following three research questions: 1. Does psychosocial stress impair FER in individuals with BPD? (Study 1) 2. Does (perceived) social exclusion result in lower emotional empathy in women with BPD? (Study 2) 3. Will social exclusion result in less prosocial behavior in women with BPD compared to healthy controls (HC), and will this correspond with changes in salivary testosterone levels? (Study 3) In Study 1, we tested FER after psychosocial stress induced with the Trier Social Stress Test. In Studies 2 and 3, we examined whether social exclusion compared to overinclusion induced with the virtual ball game Cyberball affected empathy (Study 2), prosocial behavior (Study 3), and salivary testosterone levels (Study 3). The main findings of Study 1 were that women with BPD did not differ from healthy women in FER performance and that this was not influenced by psychosocial stress. Study 2 revealed that women with BPD showed less emotional empathy for positive emotions than HC but not for negative emotions after both social exclusion and overinclusion. This effect was most pronounced after social exclusion. Furthermore, women with BPD did not differ from HC in cognitive empathy, which was unaltered by the social stressor of social exclusion. The BPD group reported more negative feelings and higher threatened psychological needs and felt more excluded than HC in both conditions. In Study 3, women with BPD showed higher prosocial behavior than HC in terms of sharing more money but did not differ in their punishment behavior in economic exchange games. Both sharing and punishment behaviors were unaffected by social overinclusion or exclusion. Moreover, women with BPD displayed higher testosterone levels than HC, which did not change in response to the Cyberball manipulation. Contrary to our expectations, the results of this dissertation suggest that women with BPD do not significantly differ from HC across various facets of social cognition following different forms of social stress. Cognitive aspects of social cognition, such as FER and cognitive empathy, appear resilient to stress. Emotional responses, on the other hand, particularly empathy for positive emotions, appear to be more vulnerable to social stress in general and to social exclusion in particular. Findings of greater prosocial behavior in women with BPD than in HC challenge the hypothesis that women with BPD respond to social stress with an aggressive or antisocial “fight-or-flight” reaction. Individuals with BPD, who are highly sensitive to exclusion, may display outward prosocial behavior as a strategy to avoid further rejection and to maintain the relationship. In clinical practice, the findings of this dissertation may be applied in therapeutic interventions for training interpersonal and stress-tolerance skills. The observed elevated baseline testosterone levels observed in women with BPD may influence social behaviors, potentially contributing to the overall BPD pathology. To possibly establish causality, future research should further elucidate this association using methods such as ecological momentary assessment in longitudinal study designs. Overall, the findings of this dissertation contribute to closing a gap in the literature toward a more nuanced understanding of social cognition after social stress in patients with BPD.  

This thesis is about the design and synthesis of redox-active mechanically interlocked molecules. The work combines a designer approach towards the form and structure of these molecules with scientific method in endeavours of preparing these molecules.

The general field of the work is in supramolecular chemistry and concerns thinking on how parts of a molecule work together in the whole structure.

The work may be interesting for scientists working with mechanically interlocked molecules, systems chemistry, systems biology as well as researchers in organic chemistry, as this is the chemistry that was used in the synthetic procedures.

To summarise, the work explores how parts of mechanically interlocked molecules relate with each other, how they move and rearrange. Synthetic strategies toward making these molecules are explored and presented in five project-based chapters.

The dissertation addresses the lack of in-depth research that thoroughly compares the thoughts of Heidegger and Benjamin. Existing literature is dominated by anecdotal juxtapositions. While Heidegger’s and Benjamin’s works offer numerous potential points of comparison, it has yet to be clarified how these parallels align with Benjamin’s well-known critique of Heidegger. In what follows, I compare Heidegger’s deconstruction with Benjamin’s translation. The research hypothesis posits that both concepts are rooted in phenomenology, particularly in Husserl’s method of phenomenological reduction. While Heidegger’s connection to phenomenology is extensively documented, Benjamin’s affinity with it has largely gone unnoticed. Accordingly, this thesis provides the first comprehensive account of the phenomenological aspects of Benjamin’s early thought. My central argument is that while both Heidegger and Benjamin employ phenomenological reduction in their early work, they do so from profoundly different metaphysical perspectives. As a result, the sense and trajectory of their phenomenological reductions diverge significantly: Benjamin’s approach remains closely aligned with Husserl’s original intent, whereas Heidegger’s, as Husserl himself rightly observed, does not.

Bacterial infections are one of the leading causes of death, which have become a major threat to human health. Many infections are attributable to Gram-negative bacteria like Neisseria meningitidis or Acinetobacter baumannii. The number of infections has drastically increased due to treatment limitations and the rise of antimicrobial resistance. Unfortunately, as traditional antibiotics are no longer effective, alternative strategies are needed to fight bacteria and the associated diseases. Monoclonal antibodies (mAbs) and vaccination are two approaches which confer protection and prevention with a much lower probability of resistance emergence. Some commercial glycoconjugate vaccines using native capsular polysaccharides (CPSs) are available, but the isolation of CPS is complex and may lead to impurities. To address this, synthetic and pure oligosaccharides that mimic native CPS and are conjugated to a carrier protein can be used to ultimately promote specific immune responses. In the first part of my thesis, I demonstrated that using a fluorinated synthetic glycan conjugated to carrier proteins induced a strong immune response. The fluorinated glycan mimicked the epitope of N. meningitidis serotype C, which was conjugated to two carrier proteins, CRM197 or Porin A (PorA), respectively. After immunization, I showed that the raised antibodies recognized the fluorinated glycan as well as the native epitope of serotype C. Moreover, as PorA is expressed by serotype B, employing this carrier protein led to the creation of a bivalent glycoconjugate targeting both serotypes. I also proved the protective effect of the glycoconjugates since the pathogens were successfully cleared in vitro by the action of the complement and phagocytic cells, induced by the generated antibodies. Consequently, this strategy presents as a novel platform for developing glycoconjugate vaccine leads. In the second part of my thesis, I worked on the development of mAb candidates and vaccine leads against A. baumannii. On one hand, I produced three mAbs against the K1 capsule of A. baumannii. The mAbs recognized specifically both the synthetic glycan and the native CPS K1. The protective effects of the mAbs were studied in vitro, demonstrating their activity in reducing the bacterial load of A. baumannii. On the other hand, I also developed glycoconjugate vaccine leads containing synthetic oligosaccharides mimicking CPS types K1 and K3 of A. baumannii. The immunized mice produced a robust and long-lasting immune response, generating different subclasses of IgGs that are linked to a higher protective potential. The semi-synthetic glycoconjugates induced the production of antibodies with higher or similar binding to native CPS compared to those generated by the traditional CPS-based glycoconjugates, which were also evaluated in mice. Moreover, the protective activity in vitro induced by the semi-synthetic glycoconjugates was superior. An in vivo study with a mouse model of A. baumannii infection revealed that immunization with the semi-synthetic glycoconjugate candidates led to the reduction of bacterial burden in organs and alleviated disease symptoms, especially against the strain with K1 capsule. However, the results obtained with the K3 CPS strain showed a moderate efficacy, likely due to its higher virulence or the higher inoculum dose. In summary, my work during this thesis demonstrates that the utilization of synthetic oligosaccharides is a great alternative for the generation of effective glycoconjugate vaccine leads and mAbs against N. meningitidis and A. baumannii. Therefore, making them promising approaches for the treatment and/or prevention of infections, especially in high-risk or immunocompromised patients.

En esta investigación me ocupo de analizar la transición a la vida civil de los excombatientes músicos de las FARC-EP (Fuerzas Armadas Revolucionarias de Colombia – Ejército del Pueblo) tras la firma del acuerdo de paz en la Habana en 2016. Este análisis lo hago a la luz de sus experiencias socio-digitales, de sus prácticas musicales y de la disputa mediática visible en la construcción de la esfera pública. Por medio de un acercamiento metodológico basado en la etnografía digital, le hago un seguimiento a las biografías y a las experiencias socio-digitales de los músicos de las FARC en la etapa temprana de implementación del acuerdo de paz. El foco teórico con el que abordo mi pregunta de investigación se fundamenta en un diálogo entre la antropología digital y la antropología de la música. Este lente le da un marco al análisis de las experiencias socio-digitales de los/las firmantes de paz, con cuyas expresiones los músicos exguerrilleros habitan los espacios onlife en este periodo de transición. Explorar las formas en las que se habitan estos espacios implicaron un diálogo teórico con la definición de espacio en términos de creación de relaciones locales y transnacionales, con la resignificación de la memoria a partir de la creación archivos digitales y con la construcción de identidades y afectos. Concluyo que sus experiencias socio-digitales se han resignificado para darle voz a individualidades imperceptibles bajo el marco de la colectividad fariana y, por otro lado, que las experiencias adquiridas durante la guerra también han tenido un carácter constructivo, dinámico y creativo reflejadas en el ámbito de las producciones culturales y en las estrategias comunicativas ligadas a ellas. En ese sentido, estas experiencias han sido re-instrumentalizadas por los/las exguerrilleros/as para figurar en la esfera pública con un perfil que dista del talante guerrerista y que se orienta hacia la construcción de paz.

Biological cells interact with their environment through molecular processes in the cell membrane. By this means, the interplay between the lipid membrane and specialized membrane proteins determines cell morphology and controls a variety of specific cellular functions. For modelling these interactions on relevant time and length scales, so-called hybrid models are widely-used and established. Thereby the proteins are modelled as dicrete particles, while the lipid membrane is seen as a two-dimensional elastic continuum, whose energy is given by a Canham-Helfrich-like functional. Particularly focusing on the accessibility for efficient numerical methods and numerical analysis, this thesis investigates the somehow most detailed hybrid model. Thereby, the particles are described as discrete rigid objects with finite size, which, according to their particular properties and geometry, induce local constraints along the membrane-particle-contour. First of all, the variational formulation of the membrane-particle hybrid model problem is provided, along with a suitable solution space, particularly incorporating the particle-induced constraints and their degrees of freedom. Furthermore, existence and uniqueness of the corresponding weak solution is proven, followed by the main part of this work - the derivation of a suitable discretization and the provision of an appropriate a priori error estimate. For discretization, the non-conforming Morley finite element is chosen. Due to its simple structure and its few degrees of freedom, it is particularly attractive. However, as Morley's element does not even provide C⁰-continuity, estimating the discretization error is not straightforward, even not for simple model problems with homogenous boundary data on convex, polygonal domains. For the membrane-particle problem, which constitutes the basis of this work, the curved boundaries, the non-homogeneous boundary conditions - particularly depending on the particles' degrees of freedom - and the lacking convexity of the domain are additionally aggravating factors.

Ziel dieser Arbeit war es, im in vivo-Teil den immunmodulatorischen Effekt nanopartikulärgebundener CpG-ODN an zehn an Sommerekzem erkrankten Pferden zu untersuchen. Dazu wurden die Tiere im Zeitraum Juni bis Dezember 2020 zweimal innerhalb von fünf Wochen in einem Abstand von jeweils zwei Tagen mit CpG-GNP behandelt. Die intrakutane Applikation erfolgte an den beiden Prädilektionsstellen Mähnenkamm und Schweifrübe. Im in vitro-Teil wurde untersucht, ob sich durch die Behandlung mit CpG-GNP immunmodulatorische Effekte nachweisen ließen. Bei jedem der fünf Untersuchungszeitpunkte wurden die Pferde und Ponys allgemein untersucht. Der allgemeinen Untersuchung schloss sich die dermatologische Untersuchung mit der Ermittlung der Ekzemerscores an. Weiterhin wurden den Pferden Serumproben entnommen, um aus ihnen IgE-Antikörper-Titer und die Sekretion des Zytokins IL-4 zu bestimmen. Zusätzlich wurde EDTA-Blut gewonnen, um die daraus isolierten PBMC in drei Ansätzen mit CpG-GNP, CpG-ODN und GNP zu inkubieren und anhand ihrer Proliferationsraten und Zytokinprofile (eIL-4, eIL-10, eIFN-ỿ) die immunstimulatorische Wirkung zu untersuchen. Des Weiteren wurde bei den Tieren der Sommerekzemgruppe bei der Erst- und Abschlussuntersuchung ein Intradermaltest mit fünf Allergenen durchgeführt. Mit dem in der vorliegenden Studie angewandten Behandlungsschema der CpG-GNP konnte über den gesamten Studienverlauf ein signifikant positiver Effekt auf die klinischen Symptome des Sommerekzems der behandelten Pferde und Ponys nachgewiesen werden. Zwischen den einzelnen Untersuchungsterminen in den Heimatställen wurden die Symptome und Ekzemerscores durch die Besitzer ermittelt. In weiterführenden Studien sollte eine zeitgleiche Einbestellung aller Probanden stattfinden, um unter gleichen Witterungsbedingungen eine optimale Vergleichbarkeit der symptomatischen Besserungen zu gewährleisten. Um die Wetterverhältnisse und die Vergleichbarkeit der SE-Symptome auch während der Betreuung in den Heimatställen sicherzustellen, sollten sich die Ställe aus logistischen Gründen in einer Region befinden. Weiterhin sollte die Expression von IL-4 vergleichend sowohl in Serumproben als auch in Hautbiopsien aus Läsionen bestimmt werden. Dabei wäre zu überprüfen, ob die Messung in Hautbiopsien betroffener Pferde die aussagekräftigere diagnostische Methode für das Krankheitsbild des Sommerekzems darstellt. Weiterhin ist auch die Bestimmung zusätzlicher bzw. anderer Zytokine zu bedenken, um die Modulation der Immunreaktionen von SE-Patienten zu überprüfen und zuverlässig nachzuweisen. Im in vitro-Teil der Studie konnte für die Zellproliferation und für die Expression der bestimmten Zytokine aufgrund der unerwarteten Beobachtungen und unplausiblen Ergebnisse keine sichere Aussage zur immunmodulatorischen Wirkung der CpG-GNP gemacht werden. So stiegen die Konzentrationen von eIL-4, eIL-10 und eIFN-γ nach der Behandlung der Sommerekzempatienten statistisch signifikant an- abhängig von der jeweiligen Konzentration der CpG-GNP, der CpG-ODN und der GNP. Auch die PBMC wiesen nach Inkubation konzentrationsabhängig sowohl durch CpG-ODN, CpG-GNP als auch durch GNP eine Stimulation auf. Gelatinenanopartikel werden als immunologisch inertes Transportsystem verwendet. Ein immunmodulatorischer Einfluss von GNP wurde bisher nicht beschrieben. Anhand der Beobachtungen und Ergebnisse wurden zwei Annahmen in Hinsicht auf die Ursachen getroffen. Die erste Annahme beinhaltete eine fehlende Sterilität als Ursache für den immunmodulatorischen Einfluss der GNP, während die zweite Annahme die Ursache in den Eigenschaften der verwendeten A-Gelatine vermutete. Weiterführende Studien sind sinnvoll, um diese Annahmen und den potenziell immunmodulatorische Einfluss von Gelatine bzw. Gelatinenanopartikel unter Verwendung verschiedener Gelatine-Typen zu untersuchen.

This doctoral work focuses on the epidemiology and public health implications of non-malarial febrile illnesses (NMFIs) in endemic regions. The research delivers a comprehensive investigation of leading causes of NMFIs in febrile patients in Africa and is the first to present them in proportional morbidity rates, an important health metric that shows the relative importance of clinically relevant aetiological agents. While there was a paucity of relevant data across the continent, a remarkable diversity of bacterial, viral, fungal and parasitic infectious agents was found, with most being observed from blood and/or serum samples using both direct and indirect methods. Bacterial agents were the most prominent causes of non-malarial fevers, with viruses following closely. The first meta-analytic summary estimates of selected agents in African patients were also estimated from the work, with Streptococcus being detected using direct methods in 3.2% of the 241,499 patients investigated. A need for more fever studies to even out the regional disparities observed on the continent is discussed, with harmonised protocols for patient selection and diagnosis being needful to lower the high study heterogeneity seen for various agents. An in-depth investigation of febrile patients from Garissa County of Kenya, an arid and semiarid region of Kenya revealed further understanding of NMFIs in an endemic region. A high presence of Brucella was observed (only B. melitensis was found) in the patients examined (19.4% by PCR), much higher than the African average meta-analytic estimates of 3.1% for pathogenic brucellae. Additionally, 1.7% of patients were PCR positive to P1 subclade (formerly termed pathogenic) Leptospira and none (<1%) to C. burnetii which are leading zoonoses prioritised by the country’s health authorities for control. Younger patients (5-17 years old) were at higher odds of being seropositive to leptospires and C. burnetii than adults, showing the urgent need for surveillance and prevention measures to protect vulnerable populations. A metagenomic shotgun sequencing of serum from selected patients also revealed Streptococcus and Moraxella to be possible bloodstream infections, showing the need for the country to expand its surveillance efforts for common but under-investigated bacterial agents using untargeted sequencing or multiplex detection assays. Additional longitudinal follow-up of small ruminants in neighbouring Tana River County presented the country’s first incidence rate estimates for these infectious diseases in animal hosts. A high incidence of Leptospira and C. burnetii was observed in the animal hosts as indicated by seroconversions, and none were observed for Brucella spp. The country lacks a systematic prioritisation of animal diseases which suggests that zoonoses that have a high public Health impact may be overlooked, thereby leading to exposure of vulnerable human populations. There is a need for the adoption of prevention strategies such as vaccinations of humans and animals alike, the use of personal protective equipment and biosecurity measures to Prevent occupational exposures, and treating foods to prevent ingestion of contaminated animalsource foods. Additionally, avoiding contaminated water sources and protecting food stores from reservoir animals such as rodents is vital to prevent exposure.