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Quantum Metrology of Newton's Constant with Levitated Mechanical Systems
No full textLevitated mechanical systems are emerging as powerful tools in precision sensing and tests of fundamental physics. By trapping small particles in near vacuum using optical or superconducting techniques, these systems provide a highly stable environment that enables force sensitivities at the atto-Newton scale. Their low dissipation, long coherence times, and compatibility with quantum state preparation make them promising candi- dates for probing weak forces at short length scales and for testing the interface between quantum mechanics and gravitation. In particular, they have been proposed for next- generation measurements of Newton’s gravitational constant G, which remains the least precisely known fundamental constant.
This thesis investigates how magnetically levitated systems in superconducting traps can be used for quantum-enhanced estimation of G, for studying gravitationally induced entanglement between mesoscopic objects, and for improving our understanding of the magnetic trapping potentials employed in these setups. We present a quantum metrolog- ical scheme in which two magnetically levitated ferromagnetic spheres oscillate harmoni- cally in superconducting traps and interact only via their mutual gravitational potential. From the effective Hamiltonian we show that the gravitational interaction produces a phase shift in the system’s normal modes, giving rise to a mechanical interferometer whose phase encodes information about G. Using tools from Gaussian quantum information, we compute both the quantum and classical Fisher information to quantify the sensitiv- ity with which G can be estimated. We consider projective and continuous general-dyne measurement strategies and include realistic noise sources such as mechanical damping, thermal fluctuations, and Casimir interactions. Under experimentally motivated param- eters, our results indicate that the relative uncertainty δG/G can in principle be reduced by up to four orders of magnitude relative to current CODATA values, with around a two-day measurement time.
We additionally analyse entanglement generated by gravitational coupling in this sys-
tem using logarithmic negativity as a quantifier, and study how gravitationally induced correlations depend on the initial Gaussian states, damping, temperature, and measure- ment strategy. Upper bounds on achievable entanglement are identified for coherent and squeezed initial states, and these bounds are extended to continuous measurement schemes. This analysis clarifies which regimes of gravitationally mediated entanglement are likely to be experimentally accessible in the near term and informs the feasibility of proposed tabletop probes of quantum aspects of gravity.
Finally, we derive an exact analytic expression for the magnetic potential experienced by a point dipole trapped between two infinite superconducting plates by summing an infi- nite series of image dipoles to satisfy the Meissner boundary conditions. The closed-form potential agrees with finite-element simulations in the near-infinite-plate geometry and provides a convenient benchmark for simulating more realistic trap geometries. The ana- lytic potential exhibits a double-well structure that is relevant for orientational tunnelling studies and for trap design in experiments aimed at dark-matter detection, quantum tunnelling, and ultra-sensitive force sensing
Intrakutannaht versus Klammernaht in der Wirbelsäulenchirurgie - eine randomisierte prospektive Studie
No full textIn dieser Arbeit wurde das Auftreten von Wundheilungsstörungen in der Wirbelsäulenchirurgie mittels randomisierter und prospektiver Studie verglichen. Hierbei wurden zwei etablierte Nahtmethoden verglichen. Ferner wurde auch das kosmetische Outcome beobachtet und ausgewerte
Ex Oriente Lux: New Zooarchaeological Insights on Late Pleistocene Subsistence Strategies at Ghar-e Boof (Southern Zagros)
No full textThe Zagros Mountains lie not far away from the junction of Africa,
southwestern Asia, and Europe. During the late Pleistocene, the presence of rich
archaeological and paleoanthropological records has confirmed that during the
Late Pleistocene, these mountains and their valleys constituted biographic
corridors and migration routes for different groups of hominins, including
Neanderthals and Anatomically Modern Humans (AMHs). Despite the strategic
location of the southern Zagros of Iran, alongside the Mesopotamian plains and
the Persian Gulf, the region has remained considerably understudied in
comparison to the central and northern Zagros. Since 2004, the Tübingen-Iranian
Stone Age Research Project (TISARP) team has focused on investigating and
documenting the Paleolithic record of the Dasht-e Rostam region, in Fars
Province (Iran). Excavations at Ghar-e Boof have revealed one of the longest
Pleistocene sequences in the Zagros Mountains, which ranges from ca. 81 to 35
kya, and has demonstrated the potential of the southern Zagros to provide new
insights on settlement dynamics, techno-cultural adaptations, and the timing of
Middle and Upper Paleolithic transition. Yet, little is known about the foraging
conditions and subsistence strategies of the MP and early UP hominins that lived
across the region. Here I summarize the results of the zooarchaeological and
taphonomic analyses of the Late Pleistocene faunal assemblages from Ghar-e
Boof in order to reconstruct the paleoenvironment and hominin subsistence
strategies, and examine changes in prey choice and site occupation intensity
through time. In addition, I discuss the archaeological implications of my
investigation within the context of the Middle-to-Upper Paleolithic transition
across Eurasia.
Based on the representation of small vertebrate taxa and their ecological
requirements, the landscape surrounding Ghar-e Boof was mainly dominated by
warm, dry conditions, open meadows, and rocky slopes. Despite the aridity, there
were also some water sources nearby, and the vegetation cover consisted mostly
of grass and shrubs. Even though the environmental conditions of the Zagros are
very diverse due to their complex topography, the available paleoenvironmental
evidence from the region indicates that both MP and UP hominins inhabited and
exploited similar mosaic environments across the entire range of the Zagros
Mountains. Changes in the small mammal record of Ghar-e Boof point to a shift towards colder and/or dryer conditions around 48-45 kya, which seems to be
coeval with the Heinrich event 5, and may have impacted demographic turnovers
and cultural adaptations regionally.
I also demonstrated that the different hominins that occupied Ghar-e Boof
during the Late Pleistocene maximized their foraging efforts by targeting the
higher-ranked prey available in the nearby landscape, namely caprines. MP and
UP foragers also harvested tortoises and hunted gazelles for dietary purposes,
and on occasion they exploited carnivores, most likely for their pelts. Although
there is no unequivocal evidence for the use of small, fast-moving prey during the
MP at Ghar-e Boof, early UP Rostamian hunter-gatherers did hunt partridges,
and possibly fish. My research has shown that even if hominins relied mainly on
ungulates to meet their daily nutritional demands of meat and marrow during the
MP and early UP, their animal subsistence practices were more diversified than
previously recognized in the Zagros. The use of different types of prey and
resources allowed people of different sexes, ages, and diverse skills to actively
contribute to the subsistence economy of the group.
From a diachronic perspective, the exploitation of lower-ranked animals,
mostly partridges, relative to small, slow-moving, or easy-to-capture tortoises
increased over time. The shift in prey choice does not appear to be the result of
environmental changes. Additionally, the adoption of a new technology and more
efficient procurement methods might have lowered the capture costs of
partridges. However, there is also an increase in site occupation intensity over
the sequence, which can be tied to either larger groups of people living at the
site, longer periods of occupation, more frequent visits, or a combination of some,
if not all, of these possibilities. Changes in occupation intensity and subsistence
strategies at Ghar-e Boof are consistent with resource intensification due to
population growth and higher hunting pressures during the early UP, similar to
what many scholars have suggested for other parts of Eurasia, such as the
Levant and the Balkans. Thus, my research evinces the complex interplay of
shifts in demography, technology, socioeconomic decisions, mobility, and
occupational patterns that accompanied the onset of the early UP cultural
traditions and the definitive arrival of AMHs across the Zagros Mountains and the
rest of Eurasia
Multimodal Characterization of Microglia Heterogeneity in Aging and Alzheimer’s Disease Pathology
No full textNeurodegenerative diseases such as Alzheimer’s Disease remain a leading socio-economic challenge and have been intensely studied on the genetic level, demonstrating a significant contribution of the immune system to disease pathogenesis. However, how environmental factors influence pathology remains to be fully understood. As microglia are the main resident immune cell population in the brain, they have been studied intensely regarding their contribution to neurological and neurodegenerative diseases. In the last years, several transcriptomic studies independently identified different microglia subpopulations with a variety of functions in health and disease. However, despite many genetic studies, it is still not clear how microglia influence disease pathology, how they change during healthy aging and which regulatory factors drive the development of a specific microglia activation state. Therefore, the first study presented here used scRNA-Seq and scATAC-Seq to characterize microglia of wildtype and APP-transgenic mice of different ages. Single-cell transcriptomic and open-chromatin profiling revealed that microglia are a heterogenous cell population showing differences in number, gene expression and chromatin accessibility, not only with progressive β-amyloid deposition in the brain, but also during healthy aging. Furthermore, we describe for the first time an age-related decline of one homeostatic microglia population and a simultaneous increase of an aging-associated subpopulation, that develops and persists independent of Aβ pathology. Multimodal analysis of the microglia subpopulations identified several disease-relevant transcription factors, such as Arnt and Hif1α, and their candidate target genes. Finally, this study shows that Hif1α regulates a subset of genes that define the so-called disease-associated microglia (DAM) phenotype, and microglial knockout of Hif1α induced a shift in microglia subpopulations, reducing neuroinflammation and increasing plaque-compaction, which, in turn, limits neuritic damage.
The onset and progression of neurodegenerative diseases can be influenced by peripheral inflammatory insults such as certain diseases (e.g. diabetes, arthritis) or infections. As it has recently been shown in our lab that microglia can develop long-lasting immune memory effects in response to peripheral inflammatory insults, the second part of my PhD project was aimed at analyzing the molecular mechanisms of how peripheral inflammatory insults cause microglial immune memory. To this end, wildtype mice were stimulated with a set of pro- and anti-inflammatory cytokines or exposed to live bacterial infections and multiplex cytokine profiles were generated. In addition, a method was established that will allow us to profile fixed nuclei from mouse as well as post-mortem human tissue. In a proof of principle experiment, we could show that analyzing chromatin accessibility and gene expression in the same single-nucleus circumvents the issue of data sparsity and allows co-embedding of both datasets. This multi-omic analysis enables the identification of cell type-specific epigenetic and transcriptomic dysregulation in this and future studies
Identifizierung der Rolle des inhibitorischen Gαi3-Proteins in Adipozyten mit Hilfe Adipozyten-spezifischer Gnai3-defizienter Mäuse
No full textDissertation gesperrt bis zum 08.06.2026
Der Körper spricht. Zur Diskursivierung der Rhetorik des Körpers in der Antike
No full textDie Dissertation ist gesperrt bis zum 19. Juli 2026
Intracellular survival and escape from within macrophages by Staphylococcus aureus
No full textThe human pathogen Staphylococcus aureus is considered mainly as an extracellular, opportunistic pathogen, that causes a diverse range of illnesses worldwide. However, S. aureus employs different strategies to evade the host immune response and is able to survive within and escape from host cells, including macrophages. An agr/sae-mutant of strain USA300 is unable to escape from human macrophages but can replicate and survive within macrophages.
This study investigates whether this "non-toxic" S. aureus resembles less pathogenic coagulase-negative Staphylococcal species (CoNS) such as S. carnosus, S. lugdunensis, S. capitis, S. warneri, and S. pettenkoferi. We found that CoNS are more efficiently killed by macrophage-like THP-1 cells or human primary macrophages. While deletion of superoxide dismutases impaired S. aureus survival in primary macrophages, it did not affect survival in THP-1 cells. Expression of S. aureus-specific sodM in S. epidermidis was insufficient to protect against killing, indicating that better survival of S. aureus is not solely due to higher protection from reactive oxygen species (ROS). Notably, "non-toxic" S. aureus was insensitive to pH, whereas most CoNS were protected from phagosomal acidification. Furthermore, S. aureus can induce a previously unknown type of cell death in macrophages, with Leukocidin A/B (LukAB) playing a critical role in cell exit and host cell death. Exogenous LukAB triggers activation of the NLRP3 inflammasome, promotes IL-1ß secretion, and kills primary human monocytes. However, the intracellular role of LukAB and its effects on cell death pathways and the NLRP3 inflammasome remain unclear. Using different S. aureus strains lacking LukAB and/or with inducible LukAB expression, we discovered a decoupling of NLRP3 inflammasome activation and cell death via a non-pyroptotic route. This process depends on the CD11b receptor for intracellular LukAB but does not involve classical apoptosis or necroptosis, despite the activation of known signaling mediators. Thus, S. aureus LukAB induces a non-conventional cell death pathway in human macrophages.Die Dissertation ist gesperrt bis zum 15. Juni 2026
A multi-omics study investigating the responses of Bacillus subtilis to the antibiotic fosfomycin and the development of cell wall analysis methods
No full textDie Dissertation ist gesperrt bis zum 16. September 2026 !Die derzeitige Zunahme antimikrobieller Resistenzen und der alarmierende Mangel an neuen
Antibiotika in klinischen Studien erfordern eine Neubewertung bestehender Antibiotika für
therapeutische Anwendungen, um den aktuellen medizinischen Standard aufrechtzuerhalten.
Fosfomycin (FOS) ist ein seit langem etabliertes Antibiotikum mit einem breiten
Wirkungsspektrum gegen grampositive und gramnegative Bakterien. Durch synergistische
Effekte mit Antibiotika aus verschiedenen Klassen bietet es ungenutztes Potenzial für
Kombinationstherapien, auch gegen multiresistente Erreger. Die Untersuchung der zellulären
Antworten von Bakterien ermöglicht ein tieferes Verständnis der FOS-induzierten bakteriellen
Reaktionen, die über die Hemmung des Zielmoleküls MurA hinausgehen. Dies bildet die
Grundlage für medizinische Kombinationstherapien. Dazu wurde das Wachstumsverhalten
des probiotischen grampositiven Modellbakteriums Bacillus subtilis in Gegenwart
verschiedener FOS-Konzentrationen mittels Multi-Omics Analysen untersucht. Durch die
Hemmung des Enzyms MurA, das den ersten Schritt der de novo Peptidoglykan (PGN)
Biosynthese darstellt, greift FOS in einen streng regulierten und essenziellen bakteriellen
Stoffwechselweg ein. MurA katalysiert die Enolpyruvyl Übertragung von Phosphoenolpyruvat
(PEP) auf UDP-N-acetylglucosamine (UDP-GlcNAc), wodurch UDP-GlcNAc-Enolpyruvat
entsteht. FOS hemmt MurA kovalent durch Bindung an einen Cysteinrest im aktiven Zentrum
des Enzyms. Interessanterweise wird das native MurA-Enzym in Gegenwart von PEP an
diesem Cysteinrest kovalent modifiziert, wodurch es vor einem Angriff durch FOS geschützt
ist. Die posttranslationale Modifikation durch PEP konnte bisher nicht direkt nachgewiesen
werden, obwohl bereits existierende Kristallstrukturen von MurA darauf hindeuten. Mittels
nativer MS konnte die kovalente Bindung von PEP an beide MurA-Isoformen in B. subtilis
(MurAA und MurAB) direkt nachgewiesen und der daraus resultierende Schutz vor FOS
bestätigt werden. Die Bedeutung des Glycerin-3-Phosphat-Transporters GlpT für die
Aufnahme von FOS und der Bacillithiol-S-Transferase FosB für die Entgiftung von FOS wurde
durch chromosomale Mutanten nachgewiesen. In einem Multi-Omics Ansatz, bestehend aus
Transkriptom-, Proteom- und Metabolom-Untersuchungen, wurden die metabolischen
Anpassungen durch die Verwendung niedrigerer FOS-Konzentrationen und die Ursachen der
Zelllyse in Gegenwart höherer FOS-Konzentrationen umfassend analysiert. Die Ergebnisse
zeigten sowohl spezifische stressabhängige Reaktionen als auch stressunabhängige
metabolische Anpassungen in FOS-behandelten Zellen. Zellhüllenstress, der durch die
alternativen Sigma-Faktoren SigM, V, W, X, Y und den Transkriptionsregulator Spx kontrolliert
wird, dominierte die Antwort. Auffallend ist, dass auch die Lipoteichonsäure-, Teichosäure- und
Fettsäuresynthese sowie die Eisenhomöostase hochreguliert waren. Die PGN-Synthese war
hochreguliert, während PGN abbauenden Enzyme herunterreguliert waren. Insgesamt
regulierte FOS die katabolen Prozesse der Zelle herunter. Um FOS-induzierte
Metabolitveränderungen zu untersuchen, wurde ein LC-MS Metabolomics Arbeitsablauf mit
Schwerpunkt auf der Zellwandanalyse unter Verwendung einer Standardbibliothek entwickelt,
die alle löslichen PGN-Vorstufen enthält. Darüber hinaus wurden LC-MS- und HPLC-Analysen
entwickelt und eingesetzt, um Fragestellungen im Zusammenhang mit der Wirkung von FOS,
der bakteriellen Zellwand und dem Zuckerstoffwechsel in verschiedenen Projekten zu
beantworten. Die vorgestellte Arbeit ermöglicht ein differenziertes Verständnis der komplexen
zellulären Reaktionen auf FOS und liefert wertvolle neue Erkenntnisse über das
Zusammenspiel von Wachstumshemmung, Zelllyse und metabolischer Anpassung unter
FOS-Behandlung. Die Ergebnisse dieser Arbeit tragen zu einem umfassenderen Verstehen
bei, wie flexibel Bakterien ihren Stoffwechsel unter antibiotischen Stressbedingungen
anpassen und erweitern das Wissen im Umgang mit antimikrobiellen Resistenzen.The rising antimicrobial resistance and a critical shortage of new antibiotics in clinical trials are
forcing a re-evaluation of existing drugs for innovative antibiotic therapeutic applications to
ensure current standards of infection control. Fosfomycin (FOS) is a long-established antibiotic
with broad-spectrum activity against both Gram-positive and Gram-negative bacteria, offering
untapped potential for antibacterial therapy, including the containment of multidrug-resistant
pathogens, due to its synergistic effects when combined with antibiotics from different classes.
A detailed study of the cellular responses to FOS is hypothesised to enhance the
understanding of FOS-induced bacterial responses beyond the inhibition of the target MurA,
thereby rationalising the development of combination therapies. The probiotic Gram-positive
model bacterium Bacillus subtilis was used to re-evaluate target inhibition, investigate growth
behaviour in the presence of different FOS concentrations and study cellular responses using
multi-omics. FOS targets a tightly regulated and generally essential bacterial pathway by
blocking the enzyme MurA, which catalyses the first committed step in de novo peptidoglycan
(PGN) biosynthesis. MurA is a unique enzyme that catalyses the enolpyruvyl transfer of
phosphoenolpyruvate (PEP) to UDP-N-acetylglucosamine (UDP-GlcNAc) to form UDPGlcNAc-
enolpyruvate. FOS covalently inhibits MurA by binding to a cysteine residue in the
active site of the enzyme. Interestingly, in the presence of PEP, the native MurA enzyme is
covalently modified at this cysteine residue, protecting it from the attack of FOS. Although
MurA crystal structures suggested this post-translational PEP modification, it had not been
directly demonstrated. Native protein MS was used to reveal covalent PEP binding to both
MurA isoforms present in B. subtilis (MurAA and MurAB) and to confirm the resulting protection
against FOS. The importance of the glycerol-3-phosphate transporter GlpT for FOS uptake
and the bacillithiol S-transferase FosB for FOS detoxification was demonstrated using
chromosomal mutants that were at least five times more sensitive to the antibiotic. To
understand the metabolic adaptations induced by lower FOS levels that confer tolerance to the
antibiotic and the causes of cell lysis in the presence of higher FOS levels, the FOS-induced
responses of B. subtilis were investigated using a comprehensive multi-omics approach,
including transcriptomics, proteomics and metabolomics. The results revealed specific stressinduced
responses as well as stress-independent metabolic adaptations in FOS-treated cells.
Cell envelope stress, controlled by the alternative sigma factors SigM, V, W, X, Y and the
transcriptional regulator Spx, dominates the response to high concentrations of FOS.
Interestingly, lipoteichoic acid, teichoic acid and fatty acid synthesis were upregulated under
these conditions, along with iron homeostasis. PGN associated hits were affected in different
ways: Synthesis was upregulated and degradation enzymes were downregulated. Overall,
FOS downregulates catabolic processes. Furthermore, an LC-MS-based cell wall
metabolomics workflow was developed to monitor FOS-induced metabolite changes by semiautomated
comparison with a standard library containing all soluble precursors of PGN
synthesis. Analyses of bacterial metabolites were performed in the context of PGN and
beyond. In addition, LC-MS and HPLC analyses were developed and applied to address a
wide range of questions related to FOS action, cell wall and sugar metabolism. The study
provides a nuanced understanding of the complex cellular responses to FOS and provides
valuable new insights into the interplay between growth inhibition, cell lysis and metabolic
adaptation under FOS treatment. The results contribute to a more comprehensive
understanding of bacterial metabolic adaptation under antibiotic stress, advancing knowledge
in the fight against antimicrobial resistance and antibiotic use
Pooldance – Studiogespräch mit Julia Wahl
No full textWenn man Pole Dance hört, dann hat man oft sofort bestimmte Bilder im Kopf. Manche denken eher an Akrobatik oder Zirkus, andere an Stripclubs. Die meisten Leute haben den Begriff schon mal gehört, vielleicht können ihn einige aber auch nicht direkt zuordnen. Heute wollen wir uns also mit Pole Dance beschäftigen, wie man zu dieser akrobatischen Sportart kommt, unter anderem wie man sie als Beruf ausübt und auch, wie Wettbewerbe im Pole Dance eigentlich aussehen.
Pole Dance ist im Trend. Immer mehr Menschen, betreiben den Sport als Hobby – vor allem Frauen. Mittlerweile existieren in vielen Städten Pole Dance Studios, die meistens verschiedene Kurse anbieten. Auch in Tübingen gibt es ein solches Studio und ich freue mich sehr Julia Wahl heute hier im Studio begrüßen zu dürfen. Sie ist Gründerin und Inhaberin von „Polemotions“ in der Eulestraße. Außerdem hat sie in den letzten zehn Jahren an zahlreichen nationalen und internationalen Pole Dance Wettbewerben teilgenommen