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Einfluss des Zahnstatus und der Mikrobiota der Atemwege auf das Risiko chronischer Abstoßungsreaktionen und Überleben nach Lungentransplantation
On ikaite crystallization
The crystallization of ikaite (CaCO3·6H2O) instead of less soluble calcium carbonate polymorphs has important implications for formation pathways of calcium carbonate minerals, carbon dynamics in polar regions of Earth or paleoclimatic reconstructions. However, the crystallization of ikaite is far from fully understood. Although several conditions that promote the formation of ikaite have been identified, the occurrence of ikaite remains unclear, as fundamental kinetic aspects of the crystallization of ikaite remain largely unexplored to date. In order to contribute to a better understanding of the occurrence of ikaite, this doctoral thesis investigated the crystallization of ikaite by unraveling key aspects of nucleation, growth and persistence using experimental approaches.
As mineral surfaces are potentially effective for heterogeneous nucleation, the formation of ikaite was investigated in the presence of quartz and mica substrates at 0 °C. The study showed that mineral surfaces are an important formation parameter, which can promote the nucleation of ikaite: At supersaturations with respect to ikaite Ωikaite ≥ 15, ikaite was formed irrespective of the presence of these mineral substrates. At Ωikaite < 15, in contrast, ikaite precipitated only in the presence of the mineral substrates, while precipitation experiments in absence of these surfaces revealed the formation of the anhydrous CaCO3 minerals vaterite and calcite. Thus, the promotion of ikaite nucleation by quartz and mica prevented competing precipitation of anhydrous CaCO3 minerals and led to ikaite formation within a supersaturation range, which was much wider than under pseudohomogeneous conditions.
Furthermore, induction periods measured in both supersaturation regimes enabled the determination of the interfacial energy of ikaite nucleation. Using classical nucleation theory, the interpretation of induction periods from ikaite-forming precipitation experiments (Ωikaite ≥ 8) yielded an effective interfacial energy of nuclei of 15 ± 3 mJ/m2. This interfacial energy of ikaite nuclei is significantly lower than values reported for anhydrous CaCO3 phases and, therefore, may support the hypothesis of a low energy formation pathway of ikaite via an ordering of aqueous ion pair complexes without extensive dehydration. Moreover, such a formation mechanism is corroborated by the results of the study of ikaite growth kinetics in phosphate containing solutions at 1 °C. Applying the empirical equation R=k(Ω-1)^n, measured growth rates yielded a rate constant k = 0.10 ± 0.03 µmol/m2/s and a reaction order n = 0.8 ± 0.3. This reaction order implies a transport- or adsorption-controlled growth mechanism which supports the formation of ikaite involving the assemblage of aqueous ion pair complexes.
Apart from this finding, the experimental growth rates of ikaite provided no sign that ikaite growth is retarded by the presence of phosphate. A potential depletion of aqueous phosphate due to incorporation into ikaite was not detected. Thus, it must be assumed that carbonate anions in ikaite are not substantially substituted by phosphate, which supports the key role of phosphate as an inhibitor of anhydrous CaCO3 mineralization and as a powerful promotor of ikaite formation.
Without such an inactivation of anhydrous CaCO3 mineralization, the occurrence of ikaite was generally transient in precipitation experiments at different solution temperatures (0–20 °C). The persistence of ikaite decreased from 28 h at 0 °C to less than 4 min at 20 °C due to concomitant nucleation of less soluble vaterite and calcite. This concomitant multiphase nucleation indicated a limited applicability of Ostwald’s rule of stages. Applying classical nucleation theory, an adequate fit of nucleation rates was obtained for T = 0 °C with a kinetic pre-factor A of ikaite being at least 3 orders of magnitude larger than A of vaterite and calcite. Such a kinetic advantage of ikaite potentially originates from the specific nucleation mechanism without dehydration.
Furthermore, the ephemeral occurrence of ikaite between 0 and 20 °C supports that nucleation of ikaite is not limited to near-freezing environments per se. However, low temperatures are important for a prolonged persistence of ikaite. In order to ensure the persistence of ikaite, an inactivation of competing precipitation, for example by inhibitors, might be indispensable. An inhibition ensuring persistence of ikaite, though, most likely becomes more complex to achieve with temperature.
In summary, the studies showed that the fundamental crystallization kinetics of ikaite differs significantly from anhydrous CaCO3 minerals. The specific formation mechanism of ikaite involving the assemblage of aqueous ion pair complexes might be essential for the crystallization. The investigations also revealed that mineral surfaces have a substantial effect on ikaite formation and play a more important role for the nucleation of ikaite in manifold environments of Earth than previously assumed. Furthermore, the relation between temperature and ephemerality of ikaite was shown for the first time in detail. The observed ephemerality indicated that the extent of ikaite persistence decreases significantly with temperature. Therefore, pseudomorphs after ikaite (glendonites) very likely may serve as reliable proxies of low temperatures in most cases
Characterization of NDNF neurons in the mouse basolateral amygdala and in the primary motor cortex of a Huntington’s disease model
The basolateral amygdala (BLA) and motor cortex (M1) are both important regions involved in the regulation of complex behaviours and both display distinct patterns of activity and cellular alterations in neurodegenerative and neuropsychiatric conditions. The BLA, is an integrative center within the amygdala, is known to regulate responses to both positive and negative stimuli by processing and modulating fear-related behaviours. While excitatory pyramidal neurons (PNs) make up most of the BLA, local inhibitory interneurons (INs) tightly control PNs activity and thus are essential in shaping BLA responses to aversive stimuli. In this study, we explore the role of neuron-derived neurotrophic factor (NDNF)-positive INs within BLA microcircuits, focusing on their activity in response to fear-related behaviours. Using in vivo Ca2+ imaging, we identified two distinct ensembles of BLANdnf neurons which show opposite activity patterns during contextual fear conditioning and exposure to the predator odour trimethylthiazoline (TMT). Optogenetic loss-of-function studies indicate that BLANdnf neuron activity promotes freezing behaviour in response to aversive stimuli, suggesting a functional role in mediating fear responses. Additionally, monosynaptic tracing reveals significant inputs from the cortical amygdala (CoA) to BLANdnf neurons, emphasising their involvement in processing odour-induced fear. Parallel to this study, we examined the role of NDNF INs in the primary motor cortex (M1) within the context of Huntington’s disease (HD), a hereditary neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms linked to progressive neurodegeneration in the cortex and striatum. In the R6/2 mouse model of HD, we used single-nuclei RNA sequencing (snRNA-seq), ex vivo patch clamp recordings, and in vivo two-photon Ca2+ imaging to investigate how NDNF INs contribute to local circuitry dysfunction over the course of HD. Transcriptomic analysis revealed that key genes associated with NDNF IN markers are downregulated at advanced disease stages in R6/2 mice compared to wild-type controls. Patch-clamp experiments indicated an increased action potential (AP) firing rate in NDNF INs within the M1 of R6/2 mice, while synaptic transmission appeared unaffected. Two-photon imaging during a running wheel task revealed increased Ca2+ activity in NDNF INs specifically at the onset of locomotion in HD mice, suggesting that these neurons may impact motor control circuits by influencing transitions between different behavioural states.
In summary, this work highlights the diverse roles that NDNF INs play in modulating neural circuitry across different brain regions and contexts, from fear processing in the BLA to motor function in the M1. In the BLA, NDNF INs influence responses to negative stimuli, potentially shaping behaviour through differential activity patterns in response to fear conditioning. In the M1, NDNF INs exhibit hyperexcitability in the context of HD, which may exacerbate cortical network dysfunction as the disease progresses. These findings emphasise the importance of local inhibitory circuits in maintaining region-specific excitatory-inhibitory balance and suggest that NDNF INs may be important in both behavioural modulation and neurodegenerative diseases
Häufigkeit von Karies und Molaren-Inzisiven-Hypomineralisationen bei 8- bis 10-Jährigen in Bayern
Single-molecule spectroscopy & super-resolution microscopy at the biochemistry bench
Single-molecule spectroscopy and super-resolution microscopy offer valuable insights into molecular dynamics but have been limited by high costs and technical complexity. These tools are mostly accessible to specialized labs with custom-built systems. This work aims to make them more affordable and accessible to a wider range of researchers, including those in smaller or resource-limited labs.
A major challenge in single-molecule experiments is the variability in experimental setups, often due to the use of home-built systems, a limitation common across all single-molecule techniques. In the context of smFRET, which this study focused on, applying established data correction routines enabled reliable and comparable results across different setups. The most critical parameter influencing data accuracy was the gamma factor, which accounts for differences in the quantum yields of the donor and acceptor fluorophores, as well as the wavelength-dependent detection efficiencies of the point detectors. However, its overall impact was minimal given the typical FRET efficiency differences observed in biomolecules, underscoring the importance of thoughtful protein and fluorophore design to minimize variability.
Comparisons with other techniques, like Pulsed Electron-Electron Double Resonance (PELDOR) and anomalous X-ray scattering interferometry (AXSI), confirmed that smFRET provides consistent distance measurements. Discrepancies arose due to fluorophore-protein interactions but could be mitigated through careful experimental design.
A key development of this work is Brick-MIC, an affordable, open-source platform for single-molecule experiments. Built with 3D printing and open-source software, Brick-MIC allows researchers to customize setups at a fraction of traditional costs. It supports techniques like smFRET, fluorescence correlation spectroscopy (FCS), and super-resolution imaging, making these tools more accessible to the scientific community.
In a simplified iteration, a blue-green FRET system was created using a 488 nm laser, making it cost-effective while still providing valuable insights into biomolecular conformational changes. This system, while lacking stoichiometric information, enables the observation of biomolecule movements, catering to application-driven studies.
Additionally, Brick-MIC was applied to nanoparticle detection, specifically identifying SARS-CoV-2 virus particles. By combining microfluidics, fluorescence correlation spectroscopy, and dual-layer detection strategies, this work enabled rapid and specific virus detection, demonstrating the practical applications of this affordable platform in diagnostics and public health
Die Entwicklung der ästhetischen Chirurgie in Deutschland, Frankreich und im angelsächsischen Raum in der ersten Hälfte des 20. Jahrhunderts
Ab Ende des ausgehenden 19. Jahrhunderts überrollte ein Beauty-Boom die Gesellschaft in Westeuropa und zog auch die Medizin in Ihren Bann. Aus diesem kulturellen Kontext heraus entwickelte sich in der plastischen Chirurgie eine ästhetische Ausrichtung, die den Wünschen und der Sehnsucht der Menschen nach jugendlichem Aussehen und Schönheit entgegenkam. Die operativen Bemühungen konzentrierten sich nun vor allem auf das Gesicht, das nach der damaligen Vorstellung die menschliche Identität definierte und gleichzeitig die objektive Zugehörigkeit zu einer bestimmten Gesellschaftsschicht abbilden sollte. Für ein junges und schönes Antlitz waren die Menschen, insbesondere die Frauen und auch bereits die Männer, bereit, sich nicht nur mit äußerlich und innerlich wirkenden Mitteln zufrieden zu geben, sondern auch chirurgische Eingriffe in Kauf zu nehmen.
Diesen sozialen Schichten überspannenden Trend greift die vorliegende Arbeit mit der Zielsetzung auf, im Rahmen einer vergleichenden Studie die Entwicklung der ästhetischen und plastischen Chirurgie in den verschiedenen, medizinisch richtungsweisenden und relevanten Ländern zu untersuchen. Dazu gehörten insbesondere der deutschsprachige Raum mit dem Deutschen Reich, Frankreich und der angelsächsische Sprachraum mit Großbritannien und den Vereinigten Staaten von Amerika. Die Arbeit basiert auf einer umfangreichen Literaturrecherche von Primär- und Sekundärliteratur. Die Primärliteratur wurde dabei anhand des Index Medicus und international relevanter Fachjournale im Zeitraum von 1885 bis 1965 analysiert.
Die Autorin hat mehrere Themenfelder untersucht: Wie hat sich die plastische Chirurgie seit Beginn des 20. Jahrhunderts und seit ihren Ursprüngen geformt und entwickelt? Durch welche Entwicklungen waren ästhetische Eingriffe und besonders das Facelift überhaupt möglich? Zum zweiten, hatte die Arbeit das Ziel die Pioniere der Faceliftchirurgie und deren Operationstechniken herauszuarbeiten. Der dritte Schwerpunkt dieser Arbeit untersuchte schließlich die zeitliche Genese des Begriffes des Facelifts und wie dieser Begriff in die deutsche Sprache Eingang fand.
Die Arbeit kam zum Ergebnis, dass nur durch die neuen medizinischen Entwicklungen, wie beispielsweise bessere Anästhesietechniken, das keimfreie Operieren oder die subkutane Nahttechnik, sich die Schönheitschirurgie entwickeln konnte. Aus den Erfahrungen der Kriegschirurgie liessen sich wichtige, neue Erkenntnisse in der Vaskularisation, der Durchblutung des Gewebes und der Hautablösung gewinnen, welche zu einer grossen Sicherheit bei der Durchführung des Facelifts führte. Die Faceliftpioniere in den unterschiedlichen Kulturräumen unterscheiden sich im Hinblick auf Nahtmaterial, Schnittlänge, Ort der Schnittführung, sowie in ihrer Innovation. Die zeitliche Komponente der Veröffentlichungen war im angelsächsischen Raum, mit vor allem den Vereinigten Staaten von Amerika, sowie in Frankreich weitaus früher als in Deutschland. Auch hat die Studie gezeigt, dass bereits weit vor Erich Lexer großflächige Hautunterminierungen bei den Ophthalmochirurgen durchgeführt wurden. Die Arbeit zeigt zudem, dass der Terminus des Begriffes Facelift eine amerikanische Wortschöpfung aus den 20er Jahren ist, die in den 60er Jahren des 20 Jahrhunderts in die deutsche Sprache Einzug fand.From the end of the 19th century, a beauty boom swept through Western European and American society. Based on this cultural context, plastic surgery developed an aesthetic orientation that met people's desires and longing for a youthful appearance and beauty. Surgical endeavours now focused primarily on the face, which, according to the prevailing opinion of the time, defined human identity and at the same time represented objective membership of a particular social class. For a young and beautiful face, especially women and even men, were prepared not only to be satisfied with external and internal means, but also to accept surgical interventions.
This thesis takes up this trend, which spans social classes, with the aim of analysing the development of aesthetic and plastic surgery in the various medically trend-setting and relevant countries as part of a comparative study. This included in particular the German-speaking area with the German „Reich“ and France and the Anglo-Saxon world with Great Britain and the United States of America.
The study is based on an extensive collection and review of the available surgical literature published at this time. The time slot for the analysis of the primary literature was based on the Index Medicus and internationally relevant specialist journals from 1885 until 1965.
The author has analysed several topics: Firstly, how has plastic surgery been shaped and evolved since the beginning of the 20th century and since its origin. Which technological, social and medical developments were essential for the establishing of aesthetic surgery and facelift surgery. Secondly, this work aimed to identify the pioneers of facelift surgery and their surgical techniques. Finally, the third focus of this thesis examined the chronological genesis of the term facelift and how this term found its way into the German language. The paper came to the conclusion that cosmetic surgery was only able to develop as a result of new medical developments such as better anaesthesia techniques, better cutting techniques as well as antisepsis. Thus, the development towards an aesthetic facial surgery branch was possible.
The experiences of wartime surgery provided important new insights into vascularization, tissue perfusion and skin detachment, which led to a high degree of safety when performing facelifts. The facelift pioneers in the different cultural zones differed in terms of suturing material, incision length, incision location, innovation as well as chronology of publication. The study has shown that the time component of the publications was much earlier in the Anglo-Saxon region, particularly in the United States of America, and in France than in Germany. Moreover, research has shown that large-area skin undermining in order to close large areas of undereye defects, was already being performed by ophthalmologic surgeons long before Erich Lexer. Finally, the study shows that the term facelift is an American neologism from the 1920s that found its way into the German language replacing the German term “Gesichtsspannung”
Enantioselective approach to 1-benzyltetrahydroisoquinolines and their five-, seven-, and eight membered homologues
Essays in public economics
This dissertation consists of six independent essays in public economics. Chapter 1 examines the impact of foreign corporate ownership on the U.K. housing market, showing how offshore investments influence house prices and vacancy rates. Chapters 2 and 3 develop and apply theoretical frameworks to evaluate the taxation of couples, focusing on efficiency, welfare, and political economy considerations. Chapter 4 extends this analysis by incorporating stated preferences from survey data, offering insights beyond standard analyses based on material self-interest. Chapter 5 investigates the validity of hypothetical survey methods for measuring fairness preferences, comparing them to results from an incentivized experiment. Chapter 6 analyzes work-life balance policies in Germany, using quasi-experimental variation to estimate behavioral responses and welfare effects. Together, the essays offer new perspectives on multidimensional inequalities, fairness preferences, and policy instruments
Reference patterns of semantic paradoxes and the problem of their graph-theoretic characterization
This thesis is a contribution to the field of semantic paradoxes. It joins a tradition of works that investigate the questions of why certain referential structures of sentences or sentence systems lead to semantic paradoxes.
The approach presented in Chapter 2 is language-independent. The fundamental concept it is based on is that of a Boolean network. Other frameworks of the tradition that could be described as graph-theoretic approach to the semantic paradoxes can be embedded in ours straightforwardly.
As in various other accounts, reference patterns are formally conceived as directed graphs. A question every graph-theoretic account has to answer is what graphs should be conceived as being potentially paradoxical. The answer is not straightforward, since graphs that occur as reference graphs of paradoxical sentences usually do so not exclusively, but occur also as reference graphs of sentences that are not paradoxical.
I will suggest three candidates for the class of all potentially paradoxical directed graphs: dangerous digraphs, digraphs of infinite character and not strongly kernel-perfect digraphs. Each of them captures a different aspect of the intuition one might have about potentially paradoxical graphs and each gives rise to a characterization problem, i.e., the problem of finding a graph-theoretic property that is a necessary and sufficient condition for a graph to be a member to this class. To each of the three characterization problems I conjecture a solution. A directed graph is conjectured to be dangerous if and only if it contains a directed cycle or a finitary inflation of the Yablo-graph (i.e., the reference pattern of Yablo's paradox); it is conjectured to be of infinite character if and only if it contains a finitary inflation of the Yablo-graph; and it is conjectured to be not strongly kernel-perfect if and only if it contains an odd directed cycle or an odd finitary inflation of the Yablo-graph. It will be investigated how these conjectures are interrelated.
The goal of Chapter 3 is to show that any Boolean network (and the question of whether it has a fixed point in particular) can be analyzed in terms of an associated directed graph. Such a graph is called a characteristic digraph of the Boolean network and contains more information about it than a reference graph. This reduces the question of whether a sentence system is paradoxical to a purely graph theoretic one. In Chapter 4 it is shown that all three criteria conjectured as sufficient and necessary are sufficient indeed. In Chapter 5 it is shown that the criterion for dangerous digraphs is necessary under certain additional assumptions