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Linking observations and modelling to advance our understanding of spatio-temporal variations in structure and productivity of Arctic protist plankton
Get PDFThe Arctic Ocean, a critical player in global climate dynamics, is undergoing rapid and dramatic changes. This doctoral thesis explores the Arctic's intricate variability in physical, chemical, and biological processes, with a focus on the Fram Strait. The primary objective is to advance our understanding of the connections between the microbial pelagic ecosystem and organic matter cycling in the Arctic Ocean, while explicitly accounting for the variability seen in observational data. This thesis aims to unravel the complex dynamics driving temporal and spatial variations in protist plankton composition, identifying key regions crucial for discerning growth dynamics. Understanding the ranges and drivers of seasonal and inter-annual variability in these processes is critical for reliable projections of future climate change impacts on Arctic ecosystems. Combining in-situ observations, advanced modelling, and remote sensing, this work uncovers the dynamic responses of Arctic plankton to variable conditions. The findings provide vital insights into the spatial and temporal variability of Arctic protist plankton, offering a foundation for future research and helping to predict the impacts of climate change on this critical region
A Single Carrier Rotating Modulation for Modular Multilevel Converter based Isolated DC-DC Converters in EV Charging Station
Get PDFA modular multilevel converter (MMC) based isolated DC-DC converter is an interesting topology enabling medium-voltage DC (MVDC) grid-connected EV charging stations, an efficient solution for reducing power conversion stages. In modulations applied to MMC based DC-DC converters, a quasi-two-level (Q2L) modulation is suitable for medium-frequency (MF) DC-DC conversion and can reduce stresses on a transformer due to a low dv/dt characteristic. However, attention must be paid to balancing DC capacitor voltages between the submodules (SMs), and it is hard to apply the existing methods in practice because of the complex balancing algorithm. Therefore, this paper proposes a new modulation with inherent SM DC capacitor voltage balancing for the MMC, which is used as a primary converter of MVDC isolated DC-DC converters. The proposed modulation can achieve the natural balancing of the DC capacitor voltages by rotating the SM insertion duration. In addition, improved balancing of SM capacitor voltages can be achieved by applying a controller to compensate for the effects of uncertain parameters such as capacitance tolerances. The effectiveness of the proposed modulation is verified with simulation and experimental results
Überlegungen zu Ethik und Religion im Gesellschaftsbuch der Frauensozietät Tugendliche Gesellschaft: Das Beispiel der ›Gerechten‹ Herzogin Dorothea Augusta von Schleswig-Holstein-Sonderburg-Plön (1602–1682)
Get PDFIm Jahr 1619 gründete Gräfin Anna Sophia von Schwarzburg-Rudolstadt, geborene Anhalt, die Tugendliche Gesellschaft. Mit 103 Mitgliedern war sie zu ihrer Zeit die größte protestantische Gesellschaft für adlige Frauen in Deutschland. Inspiriert wurde sie von der ›männlichen‹ Fruchtbringenden Gesellschaft, die von Anna Sophias Bruder Prinz Ludwig gegründet worden war. In dieser Beziehung spiegeln sich bereits die engen dynastischen Verbindungen zwischen den beiden Gesellschaften wider, was sich auch daran zeigt, dass von den sechs schleswig-holsteinischen Mitgliedern fünf mit Mitgliedern der männlichen Akademie verheiratet waren. Nach innen betonte die Gesellschaft die Tugend der amicitia, nach außen traten die Mitglieder als Vorbilder für christliches Verhalten auf. Das Gesellschaftsbuch, das stark von Wolfgang Ratke geprägt war, legte dies ausdrücklich fest. Ratke, ein bedeutender Philosoph und Pädagoge, vertrat in seiner SittenLehr der Christlichen Schule eine ausgeprägte aristotelische Ethik, und der Gesellschaftsname eines jeden Mitglieds spiegelte seine besondere Tugend wider. So wurde Herzogin Dorothea Augusta von Schleswig-Holstein-Sonderburg-Plön (›Die Gerechte‹) die herausragende aristotelische Geistestugend der Gerechtigkeit verliehen, was die starke Betonung der Verbindung von aristotelischer und christlich-lutherischer Ethik durch den Verein unterstreicht.In 1619, Countess Anna Sophia von Schwarzburg-Rudolstadt, née Anhalt, founded the Virtuous Society (Tugendliche Gesellschaft). With 103 members, it was the largest Protestant society for aristocratic women in Germany at the time. Inspiration had come from the ›male‹ Fruitbearing Society (Fruchtbringende Gesellschaft), founded by Anna Sophia’s brother, Prince Ludwig. This relationship already reflects the close dynastic ties between the two societies, further evidenced by the fact that of the six members from Schleswig-Holstein, five were married to members of the male academy. Internally, the association emphasized the virtue of amicitia; externally, the members acted as role models of Christian conduct. The ›society’s album‹ (Gesellschaftsbuch) specified this explicitly, heavily influenced by Wolfgang Ratke. An important philosopher and pedagogue, Ratke’s SittenLehr der Christlichen Schule manifested distinctly Aristotelian ethics, and each member’s society name (Gesellschaftsname) reflected her particular virtue. Accordingly, Duchess Dorothea Augusta von Schleswig-Holstein-Sonderburg-Plön (›The Righteous‹ / ›Die Gerechte‹) was granted the outstanding Aristotelian intellectual virtue of Justice, underscoring the association’s strong emphasis on the connection between Aristotelian and Christian-Lutheran ethics
Polymerbasierte Implantate für die kontrollierte Freisetzung von Allergoid für die Allergen-Immuntherapie
Get PDFIn allergen immunotherapy (AIT) allergy remission is achieved through regular application of allergy-triggering substances (allergens), either in their native or chemically modified form (allergoids). One of the main factors affecting AIT efficiency is the low adherence. The development of a subcutaneous implant loaded with an allergoid represents a new and innovative route of administration for controlled release of the allergoid, resulting in sustained drug levels over several months with minimized applications. The presented work reports the development of implants based on the biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) for a controlled long-term release of birch allergoid. Various implant formulations based on the PLGA polymers RG 504 H and RG 756 S were manufactured by hot melt extrusion using a twin-screw extruder. Characterisation of the implants by scanning electron microscopy and quantitative determination of the allergoid within the extrudate confirmed the successful implementation of the process. The structural integrity of the allergoid in the various implant formulations was investigated by combined evaluation of different physicochemical methods, including FTIR, SEC, DLS and IEF, while the preservation of the immunological properties was analysed by determination of IgG- or IgE-binding activity. The allergoid showed high stability towards the high process temperatures of up to 95°C which was further improved by the inclusion of a protein-stabilising agent (trehalose). In-vitro release experiments demonstrated a long-term release of the allergoid from PLGA-based implants for up to 40 weeks. Polymer- and formulation-dependent influences on the erosion behaviour of the polymer and the release of the allergoid were observed.The presented results could serve as a base to develop a platform technology for the future treatment of IgE-mediated allergies
Microbial dynamics in health and disease: from strain-level adaptations to microbe-microbe interactions in the gut microbiome
Get PDFThis thesis deals with the evolution of bacteria in the gut microbiome, and the potential of therapeutic exploitation. The gut microbiome changes in a predictable manner during disease. However, strain-level changes in the gut microbiome during disease development remain unclear. Here, I explore the evolution of Escherichia coli, a commensal of the human gut microbiome, in a mouse model of inflammatory bowel disease through a multi-omics approach to understand the bacterial adaptation to host inflammation. In other chapters of the thesis, I explore how commensal bacteria in the gut microbiome may interact with each. Bacterial interactions between naturally co-existing Bacteroidetes bacteria within the gut microbiome could potentially dictate the composition and therefore the functional potential of the gut microbiome. Finally, I also explore the function of a specialized bacterial secretion system, called the type VI secretion system (T6SS), in a gut commensal to understand its effect on naturally co-existing strains. I also perform an extensive literature review and speculate on the ecological and evolutionary factors that determine the observed presence-absence pattern of T6SS across bactreria taxa
Genomics of in vitro dauer juvenile recovery of the entomopathogenic nematode Heterorhabditis bacteriophora in monoxenic liquid culture with its symbiotic bacterium Photorhabdus laumondii
Get PDFThe entomopathogenic nematode (EPN) Heterorhabditis bacteriophora is a biological control agent against insect pests. The dauer juvenile (DJ) carries cells of Photorhabdus bacteria, invades the host, and delivers bacterial cells into the insect haemolymph. The events chain in which the DJ perceives haemolymph signals and exits the arrested stage to reach sexual maturity is called DJ recovery. In monoxenic liquid cultures, DJs depend on unknown bacterial food signals to trigger the recovery. A rapid, synchronized, and high DJ recovery is a key factor for commercial production of EPN, and its further understanding is crucial to improve the mass production of EPN. By using Photorhabdus supernatant as predictor bioassay, we evaluated the DJ recovery phenotypic variability in H. bacteriophora wild type and EMS mutant lines. More than 150 single nucleotide polymorphisms (SNPs) were characterized within more than 160 mutant lines via high throughput genotyping, and four SNPs resulted robustly associated with the DJ recovery. Thereafter, we carried out a detailed geno- and phenotypic characterization of 14 Photorhabdus isolates and evaluated their influence on the DJ recovery in a set of H. bacteriophora materials. It was evidenced that the bacterial component plays a subordinate role, whereas the nematode genetic pre-disposition is a main factor in the regulation of the DJ recovery in this species. Furthermore, we conducted RNA-seq along early DJ recovery stages (0.5 – 6 h) in two mutant lines with contrasting phenotype. We determined that H. bacteriophora DJs discriminate at early stages the source of the recovery signal (bacteria or haemolymph). More than 14,000 gene models were analysed in connection with functional databases and homologies with Caenorhabditis elegans. As outcome, nine gene models are postulated as potential targets for future approaches
Massenspektrometrie-basierte Proteomanalyse ausgewählter Bakterien aus dem menschlichen Darmmikrobiom
Get PDFHuman gut bacteria live in a dynamic environment, constantly adapting their proteomes to changes like pH and nutrient availability. This study investigates how selected members of the human gut microbiome (HGM) respond to such conditions using mass spectrometry-based proteomics. Initially, the study evaluated two quantification methods—bottom-up label-free quantification (LFQ) and tandem mass tag (TMT)—in Bacteroides thetaiotaomicron. Both methods showed comparable results, indicating that this bacterium primarily alters the abundance of proteins involved in the machinery required to utilize the provided carbon sources The LFQ approach was then applied to examine proteomic changes in B. thetaiotaomicron, Blautia producta, and Bifidobacterium longum in response to different environmental pH levels. Distinct and concurrent alterations in pathway-related and stress-associated proteins were identified, including histidine biosynthesis in B. producta, nitrogen metabolism in B. thetaiotaomicron, and inositol carbohydrate metabolism in B. thetaiotaomicron and B. producta. The third project focused on identifying novel proteins, specifically short open reading frame-encoded peptides (SEP), in B. producta. The combined bottom-up and top-down proteomics analyses identified a total of 45 SEP, including previously reported SEP (BP1 to BP14). Their production varied based on environmental factors like media, pH, and supplements. The last project optimized a protocol for isolating extracellular vesicles (OMVs) from E. coli. A proteoform-directed top-down analysis, including a discovery-based open modification search, identified several potential post-translational modifications
Subphenotype-based characterisation of signalling pathways in congenital heart defects (CHD)
Get PDFCongenital heart defects (CHDs) are the most common (1 - 2 %) birth defects amongst live newborns. Despite more than 200 genes having been associated with the development of CHD, the molecular basis remains partially unclear, and only a minority of patients can be assigned to an underlying genetic variant. The identification and characterisation of novel genetic variants increases diagnostic yields, improves risk stratification and, thus, the overall clinical management of CHD patients. By analysis of an exome-based case-control study comprising of 3907 CHD-cases and 5157 population matched controls, this thesis focussed on enhancing the understanding of the genetic contribution to CHD in general and on revealing sub-phenotype specific differences. Established CHD-genes were investigated with respect to deleterious variants that might account for the patient´s phenotype. Clustering based on phenotypic subtypes followed by GO-term enrichment revealed distinct genes and mechanisms underlying the different CHD subtypes. Secondly, a permutation-based analysis of signalling pathways revealed 26 of the tested combinations to be significantly enriched. Molecular dynamics was utilised to determine the molecular mechanisms of variants localised in PTPN11 and PIK3CA. The last part was focussed on NOTCH1, a gene that has been consistently determined to be one of the key contributors to CHD. Besides truncating variants, alterations in disulfide-bonds in NOTCH1 were significantly enriched. Functional analysis showed a complete impairment of the signalling capability for the tested nonsense variants and moderately reduced capabilities for missense variants. In summary, this thesis provides novel insights into the genetic background, including specific CHD subgroups, which might offer novel surveillance and treatment strategies for CHD patients in the future
Volcanic arc island flank collapse emplacement: The complex interplay of depositional processes and longterm deposit stability
No full textVolcanic island flank collapses are the most voluminous mass movements on Earth and can trigger devastating tsunamis. With nine major events and more than 15000 casualties over the last 400 years, they pose a serious geohazard on a non-geological time scale. Hazard assessments for volcanic flank collapses require a detailed understanding of pre-condition, failure and emplacement mechanisms. However, the different processes during emplacement, the controls on the dynamics of the associated landslides, and the potential consequences of emplacement for the stability of the slope sediments are poorly constrained. Studies on ancient volcanic flank collapse deposits using high-resolution seismic data combined with drilling operations provide insight into these processes and their complex interplay. This cumulative doctoral thesis shows that the emplacement of volcanic flank collapse is an interplay of different processes over multiple phases, including initial failure of the volcanic flank and versatile interaction of the failure mass with seafloor sediments. This work also shows that the slope topography and the nature of the substrate sediment are major controls on slide dynamics and morphology, and that once a slope failure occurred on a slope, the propensity for subsequent failure is enhanced. Failure of a volcanic flank and the emplacement of the associated landslides are complex interplays of different geological and physical processes. This thesis - using the exceptional opportunity to combine high-resolution 2D and 3D seismic with drilling data from volcanic flank collapse deposits - provides new insights into this complexity
Die logische Analyse als Methode der Analytischen Philosophie
Get PDFDie Disziplin der Analytischen Philosophie hat die Sprache zum Gegenstand. Ihre Methodiken bestehen demzufolge in der Analyse der Sprache und ihrer verschiedenen Aspekte. Die logische Analyse ist eine der zentralen Methoden der analytischen Philosophie und lässt sich der Strömung der Philosophie der idealen Sprache zuordnen, deren übergeordnetes Ziel es ist, durch formale Sprachen der Logik die Mehrdeutigkeit der Sprache einzuschränken oder zu eliminieren.The discipline of analytical philosophy is concerned with language. Its methods therefore consist of analysing language and its various aspects. Logical analysis is one of the central methods of analytical philosophy and can be categorised as part of the philosophy of ideal language, the overriding aim of which is to limit or eliminate the ambiguity of language through formal languages of logic