Ludwig-Maximilians-Universität München

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    Bedeutung Autoantikörper-spezifischer Signalwege bei Pemphigus

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    Quantum gas microscopy of Fermi-Hubbard ladders

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    Understanding the behavior of strongly interacting quantum systems remains a central challenge in modern physics. The intrinsic complexity of these correlated systems has prevented efficient simulation on classical computers. Antiferromagnetic Mott insulators are an example in which competing processes of the spin and charge degrees of freedom lead to exotic phenomena like charge carrier pairing and superconductivity. The Fermi-Hubbard model, which describes the behavior of interacting fermions on a lattice, is a minimal model that captures the essential physics of strongly correlated materials. In this thesis, we use a quantum simulator based on ultracold atoms in optical lattices to perform simulations of the Fermi-Hubbard model. We realize the strongly interacting regime of this model in a ladder geometry consisting of two coupled chains. Harnessing the single-site spin and density resolution of our quantum gas microscope, we measure local and nonlocal spin and density correlations. We probe the system at temperatures around the spin-exchange energy, which marks the onset of exotic quantum many-body phenomena due to the interplay of magnetic and kinetic energy. In doped ladder systems, we directly observe the pairing of dopants, a process that is at the heart of high-temperature superconductivity. We find that pairing is strongly enhanced by suppressing one direction of dopant motion, while spin exchange persists in all directions. With such a geometry, we reach binding energies on the order of the spin-exchange energy. In contrast, if dopant movement is enabled in all directions, Pauli repulsion becomes dominant over binding. We furthermore investigate the effect of the pairs on magnetism and confirm their strong connection. At higher doping, we find correlations between pairs of dopants that are consistent with charge density order. Another result of this thesis is the realization of a finite-size and finite-temperature version of the symmetry-protected topological Haldane phase. We observe the signatures of this paradigmatic quantum phase of matter by mapping the experimental ladder system onto an antiferromagnetic spin-1 chain. We use the unique ability of our experiment to measure non-local string order parameters which allow us to distinguish between the topological and the trivial phase. We furthermore investigate the robustness of the phase for different parameter regimes and system sizes. Finally, we characterize the edge modes of the system.Stark wechselwirkende Systeme sind eine der Hauptherausforderungen der modernen Physik. Ihre intrinsische Komplexität verhindert eine effiziente Simulation mit klassischen Computern. Ein Beispiel für solche Systeme sind antiferromagnetische Mottisolatoren, in denen ein Wettstreit zwischen Spin- und Ladungsfreiheitsgraden zu exotischen Phänomenen wie Ladungs\-trägerpaarung und Supraleitung führt. Das Fermi-Hubbard-Modell, welches das Verhalten stark wechselwirkender Fermionen auf einer Gitterstruktur beschreibt, ist ein Minimalmodell welches die Physik dieser stark korrelierten Materialien wiedergibt. In dieser Doktorarbeit benutzen wir einen Quantensimulator basierend auf ultrakalten Atomen in optischen Gittern, um Simulationen des Fermi-Hubbard-Modells durchzuführen. Wir realisieren den stark wechselwirkenden Bereich dieses Modells in einer Leitergeometrie bestehend aus zwei gekoppelten Ketten. Wir messen lokale und nichtlokale Spin- und Ladungskorrelationen indem wir die Spin und Dichteauflösung einzelner Gitterplätze unseres Quantengasmikroskops nutzen. Wir untersuchen das System bei Temperaturen auf der Größenordnung der Spinaustauschwechselwirkung, welche aufgrund des Zusammenspiels von magnetischer und kinetischer Energie das Einsetzen exotischer Quantenvielteilchenphänomene markiert. In dotierten Leitersystemen beobachten wir direkt die Paarung von Dotanden, ein Prozess der der Hochtemperatursupraleitung zu Grunde liegt. Wir stellen fest, dass die Paarung stark gesteigert wird, wenn die Bewegungsfreiheit der Dotanden in eine Richtung unterdrückt wird, während Spinaustausch in alle Richtungen stattfindet. Mit einer solchen Geometrie erreichen wir Bindungsenergien die vergleichbar mit der Spinaustauschwechselwirkung sind. Im Gegensatz dazu ist Pauliabstossung dominant gegenüber der Paarbindung, wenn Bewegung in alle Richtungen ermöglicht wird. Wir untersuchen außerdem die Auswirkung der Paare auf den Magnetismus im System und bestätigen deren Zusammenhang. Bei höherer Dotierung stellen wir eine Korrelation zwischen verschiedenen Paaren fest, welche konsistent ist mit Ladungsdichteordnung. Ein weiteres Ergebnis dieser Arbeit ist die Realisierung einer Variante der symmetriegeschützten topologischen Haldane Phase bei endlicher Systemgrösse und endlicher Temperatur. Wir beobachten die Signaturen dieser paradigmatischen Quantenphase, indem wir das experimentelle Leitersystem auf eine antiferromagnetische Spin-1 Kette abbilden. Wir nutzen die einzigartigen Möglichkeiten unseres Experiments um nichtlokale Stringordnungsparameter zu messen, welche uns die Unterscheidung zwischen topologischer und trivialer Phase ermöglichen. Wir untersuchen außerdem die Robustheit der Phase bezüglich verschiedener Kopplungsparameter und Systemgrößen. Schließlich characterisieren wir die Randmoden des Systems

    Swampland distance conjectures and geometric flow equations

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    The Swampland Program aims to distinguish between those effective field theories, which can be completed into Quantum Gravity at high energies, and those which can't. The distinction between these two sets is made by the so called Swampland Conjectures which can put severe constraints on an effective field theory. These conjectures are usually motivated by general black hole arguments, holography or directly String Theory. Moreover, many of these seem to be intertwined in a web of conjectures hinting at a more fundamental principle yet to be uncovered. One of the most important and best studied conjectures is the Swampland Distance Conjecture (SDC) which lies at the heart of this thesis. It limits the scalar field space distance which can be traversed in an effective field theory before the theory has to break down due to an infinite tower of states becoming massless. Over the last years the conjecture was generalized in many different ways. For instance, a close relation to geometric flows has recently been found, which has sparked some interest in geometric flows within the Swampland community. Furthermore, the SDC is supposed to hold for geodesic field space trajectories, but it was shown that the validity of the SDC can be extended to a non-geodesic motion in field space. The purpose of this thesis now is twofold: On the one hand, motivated by the connection to the SDC new geometric flows are constructed and studied. This includes a geometric flow equation for the number of spacetime dimensions and an extension of Ricci flow which incorporates the backreaction of matter fields. On the other hand, the SDC is applied to the scenario of cosmic acceleration, which is still an open and significant problem in physics. It turns out that the non-geodesicity of trajectories is bounded by consistency with the SDC near the boundary of field space

    Causal roles of the prefrontal cortex and temporo-parietal junction in social decision making

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    Molecular and cellular mechanisms in the pathophysiology of primary aldosteronism

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    Multiphase probes of the baryon cycle from big data quasar spectroscopy

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    Simulations of the large scale structure of the Universe show the filamentary cosmic web of gas connecting galaxies and groups of galaxies with each other, with substructures that involve complex physical processes that drive the evolution of galaxies. Examples of these substructures are filaments from intergalactic medium (IGM) or the circumgalactic medium (CGM) surrounding the galaxies. These are too diffuse to be observed in emission yet, thus using luminous background sources to detect this faint gas in absorption becomes the most powerful technique available to study these structures. The use of quasar spectra as a background source can be a useful tool in a variety of contexts, including the study of the large scale structure and investigations of the environments of the quasars themselves. The aim of this thesis was to make use of large sets of data to increase the signal to noise ratio in order to identify elusive components of baryonic matter that do not necessarily emit light, but can be revealed via absorption lines in the electromagnetic spectrum of a background source. Using different ground based telescopes from optical and near UV wavelengths, we use the technique of stacking, which takes advantage of the statistically significant large amounts of data being produced. The first chapter presents an introduction to the large scale structure and other objects that were targeted throughout each project of this thesis, while presenting an overall look of the methods and instruments used. The second chapter presents a search for the IGM using FeXXI λ 1354˚A tracing 107K gas at UV wavelengths. Using more than one hundred high-spectral resolution (R∼ 49, 000) and very high signal to noise quasar spectra from the Very Large Telescope (VLT) and the Ultraviolet Echelle Spectrograph (UVES), we stacked at the redshift of known Damped Lyman-alpha (DLA) absorbers which are tracers of overdensities. We present the results of the findings and provide an outlook for the possibility of performing a similar study with future instruments. The third chapter presents a study of the Intracluster Medium using quasar spectra from the Sloan Digital Sky Survey from Data Release 16 as background sources for X-ray selected clusters from the ROSAT All Sky Survey, with spectroscopic redshift from the SPectroscopic IDentifcation of ERosita Sources (SPIDERS) program. We present the final results and compare them with simulations. Using the MgII doublet as a tracer of this 104K gas, we stack spectra at th redhift of the foreground clusters and we also compare to a known MgII absorbers sample from SDSS DR16. We find tentative evidence of MgII absorption in the whole sample. In chapter four we study outflows from Active Galactic Nuclei (AGN) by using SDSS quasar spectra and looking for MgII intrinsic absorption lines by stacking a sample of 7100 spectra from Data Release 18 (DR18). We present our results and outlook for future work. We present summary and conclusions in chapter 5, with an outlook of possibilities to continue the research in different areas that were studied during the course of this thesis

    Dissecting the role of NELL-ligands and their possible receptors in myogenesis

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    Myogenesis, the formation of skeletal muscle, occurs in four sequential, partially overlapping phases. Muscle precursor cells (MPCs) first proliferate, then migrate, differentiate, and fuse to myotubes. This spatiotemporal process is highly complex, and thus MPCs are subject to various autocrine and paracrine differentiation and migration signals. Non-myogenic muscle cells (nMMCs), such as fibroblasts or motor neurons, have also been shown to influence MPCs through several ligand-receptor pathways. Nel-related protein 1 (NELL1) and NELL2 are two ligands mainly investigated in their role in neuronal development, osteogenesis, and various tumors. More distinctively, NELL1 was shown to improve the constructive remodeling outcome in muscle injury models. In addition, NELL2 offers an interesting differential expression profile during early myogenesis. Furthermore, the Roundabout (ROBO) receptor family are the only currently known NELL receptors, and ROBOs were demonstrated to be involved in myoblast guidance and alignment. Therefore, I hypothesized that NELLs might be promising candidates that differentially influence myogenesis. Furthermore, I hypothesized that NELLs affect the cells involved in myogenesis by binding to receptors of the ROBO family. In this study, I used a gene expression-based approach and in vitro studies to examine these potentially important ligands for myogenesis. To explore the expression profile of NELLs in myogenic (MMCs) and non-myogenic muscle cells (nMMCs) separately, I bred the myogenic reporter mouse line Rosa26mT/mG;Acta1Cre. Comparison to other myogenic sequencing data revealed that NELL2 is weakly expressed by E15.5 nMMCs. During migration, myoblasts express NELL2 strongly, while interestingly, NELL2 is downregulated in early fusion. The effect of NELLs on myoblasts during various stages of myogenesis was assessed using recombinant proteins (RP) and SCP1RFP;NELL2::AP conditioned media on C2C12 cells in random migration, directed migration, alignment, and fusion assays. Aligning with the expression profile, a pro- migratory effect of NELL2 was recognized, while NELL1 was not observed to influence myoblast migration. No chemotaxis effect of NELLs on directing myoblast migration was observed. Also, no evidence of a NELL influence on alignment or fusion of C2C12 cells was shown. In sum, I identified NELL2 as a new pro-migratory ligand in myogenesis. Myoblasts during the migration phase express NELL2, which seems to work in an autocrine or paracrine manner. By NELL2 binding, C2C12 cells move slightly faster, while fusion appears to be inhibited. Future experiments should concentrate on further dissecting the effect of NELL2 on myogenesis and aim to identify if the influence is enabled by ROBO2 or another myoblast receptor.Myogenese, die Entwicklung der Skelettmuskulatur, erfolgt in vier aufeinander folgenden, sich teilweise überlappenden, Phasen. Zuerst proliferieren Muskelvorläuferzellen (MPCs), dann migrieren, differenzieren und fusionieren diese zu Myotuben. Dieser raumzeitliche Prozess ist hochkomplex, so dass MPCs verschiedenen autokrinen und parakrinen Differenzierungs- und Migrationssignalen unterliegen. Es wurde außerdem gezeigt, dass auch nicht-myogene Zellarten (nMMCs) wie Fibroblasten oder Motoneurone, MPCs über verschiedene Liganden- Rezeptor Signalwege beeinflussen. Nel-related protein 1 (NELL1) und NELL2 sind zwei Liganden, deren Rolle hauptsächlich in der neuronalen Entwicklung, Osteogenese und verschiedenen Tumoren untersucht wurden. Es hat sich jedoch auch gezeigt, dass NELL1 das Ergebnis des konstruktiven Umbaus in Muskelverletzungsmodellen verbessert. Darüber hinaus weist NELL2 ein interessantes differentielles Expressionsprofil in der frühen Myogenese auf. Zudem sind die Rezeptoren der Roundabout-Familie (ROBO) die einzigen derzeit bekannten NELL-Rezeptoren, und es wurde gezeigt, dass ROBOs an der Chemotaxis und Ausrichtung der Myoblasten beteiligt sind. Daher stellte ich die Hypothese auf, dass NELLs vielversprechende Signale sind, welche die Myogenese differenzial beeinflussen. Außerdem stellte ich die Hypothese auf, dass NELLs, die an der Myogenese beteiligten Zellen durch die Bindung an Rezeptoren der ROBO-Familie modulieren. In dieser Studie habe ich eine Genexpressionsanalyse zusammen mit in-vitro Studien verwendet, um diese potenziell wichtigen myogenese Liganden zu untersuchen. Um das Expressionsprofil von NELLs in myogenen (MMCs) und nicht-myogenen Muskelzellen (nMMCs) getrennt zu untersuchen, habe ich die myogene Reportermauslinie Rosa26mT/mG;Acta1Cre gezüchtet. Ein Vergleich mit anderen myogenen Sequenzierungsdaten ergab, dass NELL2 von E15.5 nMMCs nur schwach exprimiert wird. In der Migrationsphase exprimieren Myoblasten NELL2 stark, währenddessen interessanterweise, die NELL2 Expression in der frühen Fusion herunterreguliert wird. Der Einfluss von NELLs auf Myoblasten in den verschiedenen Stadien der Myogenese wurde mit rekombinanten Proteinen und SCP1RFP;NELL2::AP konditioniertem Medium auf C2C12-Zellen in zufälligen Migrations-, gerichteten Migrations-, Ausrichtungs- und Fusionsversuchen untersucht. In Übereinstimmung mit dem Expressionsprofil wurde eine migrationsfördernde Wirkung von NELL2 festgestellt, während NELL1 die Migration nicht beeinflusste. Es wurde kein Chemotaxis-Effekt von NELLs auf die direktionale Migration beobachtet. Auch ein Einfluss von NELL auf die Ausrichtung oder Fusion von C2C12-Zellen konnte nicht nachgewiesen werden. Zusammengefasst, habe ich NELL2 als neues Migrationssignal in der Myogenese identifiziert. Myoblasten exprimieren während der Migrationsphase NELL2, das autokrin oder parakrin zu agieren scheint. Durch eine Bindung an NELL2, migrieren die C2C12-Zellen etwas schneller, während sich eine nicht signifikante Hemmung der Fusion präsentiert. Weitere Studien sollten sich darauf konzentrieren, die Wirkung von NELL2 auf die Myogenese genauer zu untersuchen und herauszufinden, ob der Einfluss durch ROBO2 oder einen anderen Rezeptor ermöglicht wird

    A ced-3 caspase – ect-2 RhoGEF axis coordinates functional interactions between the apoptotic pathway and cell size in Caenorhabditis elegans

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    Programmed cell death via apoptosis is a common cell fate during animal development and its mis-regulation can have serious implications in diseases and disorders. Therefore, it is of high importance to study to apoptosis. The highly conserved central apoptotic pathway was initially discovered in C. elegans and consists of four genes acting in a sequence – egl-1 BH3-only, ced-9 Bcl-2, ced-4 Apaf-1 and ced-3 caspase. The most downstream gene in the pathway, ced-3, encodes for a cysteine protease called caspase, and is essential in the execution of apoptosis. A previous study in our lab had uncovered a novel non-apoptotic role of ced-3 caspase in promoting asymmetric division of C. elegans neuroblasts (Mishra et al., 2018). However, the mechanism by which ced-3 caspase promotes asymmetric division still remained to be elucidated. Thus, in my study, I aimed to decipher the mechanism(s) by which the apoptotic gene, ced-3 caspase, promotes asymmetric cell division. To that end, I first demonstrated that CED-3 caspase protein physically and directly interacts with a regulator of actomyosin contractility, called ECT-2 RhoGEF (Rho guanine-nucleotide exchange factor). Furthermore, using the NSM (neurosecretory motor neuron) lineage in C. elegans, I found that ECT-2 RhoGEF is asymmetrically enriched in the NSM neuroblast, which is the mother of the apoptotic cell. I also found that the asymmetric enrichment of ECT-2 RhoGEF depends on ced-3 caspase activity. Next, by analysing the cell size ratios of the daughters of the NSM neuroblast, my colleagues and I found that genetically, ced-3 caspase acts upstream of ect-2 RhoGEF to promote the asymmetric division by size of the NSM neuroblast. We refer to this as the ced-3-ect-2 axis. Based on these findings, we propose that the ced-3-ect-2 axis promotes polar actomyosin contractility in the NSM neuroblast, which results in its asymmetric division by size and thereby the formation of its smaller apoptotic daughter cell called the NSMsc (NSM sister cell). Molecularly, we propose that CED-3 de-recruits ECT-2 from the dorsal cortex of the NSM neuroblast before metaphase, and that this de-recruitment of ECT-2 is important for the NSM neuroblast to divide asymmetrically. 6 Next, my colleagues and I investigated the effect of the size of the smaller daughter cell, the NSMsc, on its apoptotic fate. We found that increasing the size of the NSMsc by reducing ect-2 activity decreases its probability to undergo apoptosis. Conversely, for the first time, we showed that decreasing the size of the NSMsc by hyperactivation of ect-2 can increase its probability to undergo apoptosis. Thus, we propose that cell size and apoptosis are inversely corelated – larger cells are more prone to survive and smaller cells are more prone to die. Taken together, the findings from this study have found reciprocal interactions between the apoptotic pathway and cell size. In the NSM neuroblast, the apoptotic pathway acts upstream of cell size i.e. ced-3 promotes asymmetric division of the NSM neuroblast and the formation of a smaller NSMsc. Conversely, in the NSMsc, cell size acts upstream of the apoptotic pathway i.e. the small size of the NSMsc promotes the activation/activity of CED-3 and thereby its apoptosis

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