Microbial rhodopsins and phytochromes are photoreceptors that use light to trigger biochemical processes. Upon light activation, they undergo a cyclic cascade of reactions leading to substrate transfer and/or conformational changes associated with the chromophore and protein. NmHR and UmRh1, two microbial rhodopsins, are a bacterial inward chloride pump and a fungal outward proton pump, respectively. While the role of NmHR from a marine bacterium is similar to that of the well-known archaeal inward chloride pump halorhodopsins (HsHR and NpHR), it shares a higher sequence homology with the bacterial outward sodium pump KR2. In addition, each rhodopsin contains a three-residue motif composed of amino acids involved in substrate transfer. The NTQ motif of NmHR is quite conserved in the sodium pump KR2 (NDQ), but is represented by a neutral TSA motif in archaebacterial halorhodopsins, suggesting a divergent evolution. A comprehensive mutational and spectroscopic analysis of residues known to be important for chloride transfer in archaeal halorhodopsins and for sodium transfer in KR2 revealed that chloride release and uptake in NmHR is different from that of archaeal halorhodopsins, but the architecture and residues involved in the process are more similar to KR2, despite the different charge and orientation of the transported ion. UmRh1 is a rhodopsin found in the pathogenic fungus Ustilago maydis, which causes corn smut disease. This fungal rhodopsin shares a high sequence similarity with the well-known archaeal outward proton pump bacteriorhodopsin (HsBR), especially at residues known to be important for the proton pathway of the latter. The DTD motif of HsBR is conserved in UmRh1 and is represented by a DTE motif. However, extensive mutagenesis and spectroscopy revealed that the protonation dynamics of UmRh1 are slightly different from those of HsBR, especially in the proton uptake reaction. Furthermore, the pump activity of UmRh1 is enhanced in the presence of auxins such as IAA (indole-3-acetic acid). Using time-resolved spectroscopy on UmRh1 variants in the presence and absence of IAA, a potential role for auxin was elucidated. It is involved in the enhancement of the reprotonation mechanism and the proton release reaction associated with its pathogenic role. Another aspect that has intrigued scientists over the years is the link between light and chromophore isomerization in photoreceptors, which leads to conformational changes in the protein. How does the signal propagate in the early stages of the photocycle after photon absorption? By introducing the noncanonical amino acid p-cyano-phenylalanine in NmHR and the phytochrome Agp2 into positions of conserved tryptophan residues known to be involved in conformational changes around the chromophore, preliminary results have been obtained that shed light on the protein-chromophore interaction.

In current time, bits are essential equipment in riding, used for communication between rider and horse. Their effectiveness and the effect on the horse varies depending on configuration, material, and application. Studies show that the choice of bit, along with rein tension and the horse’s head-neck position, is crucial for the horse’s welfare and performance. Misfit bits, such as those that are inappropriate in size or type, can lead to pain and injury. Common issues include mouth injuries, restrictions in breathing, and swallowing reflexes. A comprehensive study included in this work examined the use of bits in international showjumping competitions and assessed their impact on the welfare of horses. A survey of 250 riders and video analyses of 268 showjumping rounds revealed that different bits are used to address the individual needs of riders and horses. It was found that riders often use different bits for various horses and under different conditions. Mainly because horses react differently to various bits and the individual horse shows individual needs, partly due to regulations and personal preferences. The video analysis revealed that aversive movements, such as opening the mouth and other signs of discomfort, were particularly common with the use of 3-ring bits and full cheek bits. A lower incidence of aversive movements was observed in horses ridden with egg butt bits and hackamores, indicating their potentially lower level of discomfort. Additionally, the second study investigated the effects of different bits on the horses' airways, particularly on the larynx during various gaits and levels of exertion. The results showed that the type of bit had only a minimal impact on laryngeal dynamics, while the physiological state of the horse, such as exertion and head-neck position, had a significant effect on respiratory function. Overall, the studies emphasize the need for precise bit fitting and the importance of proper equipment configuration for the welfare of horses. They highlight that both bit design and its application influence horse behavior and performance. The findings underscore the importance of interdisciplinary collaboration to improve equine welfare in the sport.

Die ersten Gemeinschaften von Ackerbauern und Viehzüchtern traten im Kopet-Dag-Vorland in Südturkmenistan Ende des 7. Jahrtausends v. Chr. auf und läuteten eine lange Geschichte dörflichen Lebens in Lehmziegelbauten ein. Dieses Buch untersucht das Bauen und Wohnen der frühen Bauern und Bäuerinnen Zentralasiens anhand architektonischer Befunde und geht der Frage nach, wie diese Menschen ihre Wohnräume gestalteten. Mit einer diachronen Betrachtung und einem Fokus auf die Temporalität der Bau- und Wohnpraktiken beleuchtet der Autor sowohl den Wandel als auch die Kontinuitäten in der Gestaltung des Wohnraums, die über bemerkenswert lange Zeiträume hinweg Bestand hatten. Die Analyse erfolgt auf zwei Ebenen. Auf der Mikroebene wird die Nutzungsgeschichte und Architektur einzelner Häuser in Monjukli Depe untersucht. Dieser Fundort wurde 2010–2014 durch ein Team der Freien Universität Berlin ausgegraben. Besondere Beachtung finden die Lebenszyklen der Häuser – von ihrem Bau über die Nutzung bis hin zur Aufgabe und Umnutzung. Diese individuellen Hausgeschichten bieten ein differenziertes Bild der Raumnutzung im äneolithischen Dorf, zeigen aber auch viele Gemeinsamkeiten, die auf geteilte Vorstellungen über Hausbau, Wohnen und den Umgang mit Hausruinen hindeuten. Auf der Makroebene wird die Entwicklung des gebauten Raums über im Zeitraum 6200–2700 v. u. Z. betrachtet. Die Analyse der großflächig ausgegrabenen neolithischen und äneolithischen Fundstellen des Kopet-Dag-Vorlands ermöglicht es, langfristige Entwicklungen in der Raumorganisation dörflicher Siedlungen in der Region zu identifizieren. Diese Ergebnisse werden mit bestehenden Narrativen zur gesellschaftlichen Entwicklung in Zentralasien verglichen und tragen zu einem tieferen Verständnis von Kontinuitäten und Veränderungen in der prähistorischen Siedlungsweise bei.

Magnons and phonons are quanta of spin waves and lattice vibrations, respectively. They can be strongly hybridized to form magnon polarons, because of large magnetoelastic coupling in magnetic materials. This phenomenon was evidenced in neutron diffraction experiments revealing avoided crossings between the phonon and magnon branches. We used spin-resolved photoemission spectroscopy to investigate gadolinium and terbium. Both ferromagnetic rare earth metals have a comparable valence electronic structure but Gd is more like a Heisenberg ferromagnet where anisotropy is weak, while Tb holds much stronger magnetoscrystalline anisotropy. We found that magnon polarons play a crucial role in photohole relaxation in Tb due to the strong 4f spin-orbit coupling. The latter is very weak in Gd. Consequently, electron-phonon and electron-magnon scatterings lead to spin-dependent photohole relaxation rates in Gd. In contrast, the lifetime broadening of the occupied surface state in Tb is only weakly spin dependent and the mass enhancement parameter is twice the spin-averaged value of Gd. The formation of magnon polarons in Tb opens both minority and majority spin bands as decay channels. Besides local scattering processes driving ultrafast demagnetization, ultrafast spin transport is of enormous importance for understanding the mechanisms of many spin-dependent effects. Investigating laser-induced spin transport helps to obtain microscopic insights into ultrafast spin dynamics, and to fabricate high efficiency spintronics. We used time- and spin-resolved photoelectron spectroscopy to study an antiferromagnetically coupled Gd/Fe bilayer and observed an ultrafast 20% decrease of the spin polarization of the Gd surface state within the first 100 fs after optical excitation. The result was confirmed by a transient increase of the spin polarization in iron and corroborated by a decrease of the transient electron temperature. We conclude that spin transport across the interface drives magnetization dynamics in the Gd/Fe bilayer system. Fe acts as a very efficient spin-filter for spin-minority electrons. These findings contribute to a microscopic understanding of ultrafast spin dynamics and possible future spintronic applications.

Die Herausforderung, die sich aus der Ernährungsphysiologie bei der Pferdehaltung ergibt, liegt insbesondere in der hohen Individualität, die mit der Haltung und Nutzung von Pferden verbunden ist. Während bei klassischen Nutztieren wie Rindern, Schweinen oder Geflügel die Fütterung und Mineralstoffversorgung weitgehend standardisiert sind, ergeben sich bei Pferden aufgrund der unterschiedlichen Nutzung, Haltung und Fütterung häufig Unsicherheiten in der Bestimmung des Bedarfs und des Grundumsatzes (Suttle, 2010). Diese Unsicherheiten betreffen nicht nur den Energiebedarf, sondern auch die Versorgung mit Vitaminen und Mineralstoffen. Angesichts dieser Variabilität wird es erforderlich, nicht nur eine bedarfsdeckende Fütterung sicherzustellen, sondern auch eine präzise Aussage zur Mineralstoffversorgung treffen zu können. Zur Bestimmung der Mineralstoffkonzentration beim Pferd stehen eine Reihe von Analysemethoden zur Verfügung, wobei die serologische Analyse in der klinischen Praxis als Standardverfahren etabliert ist. Allerdings haben verschiedene Studien gezeigt, dass die Serologie nicht immer eine zuverlässige Methode zur Bestimmung der Mengen- und Spurenelementkonzentration darstellt. Dies eröffnet die Möglichkeit, alternative Analyseverfahren, wie die Untersuchung von Kotproben, als potenzielle diagnostische Werkzeuge zu prüfen. Das Ziel dieser Arbeit war es daher, die Mengen- und Spurenelementkonzentrationen in Kot- und Blutproben von Pferden aus ganz Deutschland zu analysieren. Der zentrale Forschungsschwerpunkt bestand darin, zu untersuchen, ob die Kotprobenanalyse eine geeignete Alternative zur Blutuntersuchung darstellt, um den Mineralstoffstatus von Pferden zu bestimmen. In vorangegangenen Studien wurden bereits präanalytische Bedingungen für die Nutzung von Kotproben zur Bestimmung von Mengen- und Spurenelementen untersucht, wobei ein Zusammenhang zwischen der Mineralstoffaufnahme und der Ausscheidung über den Kot festgestellt werden konnte. Daraus folgte die Annahme, dass die Kotprobenanalyse als geeignetes Verfahren zur Bestimmung der Mineralstoffversorgung von Pferden dienen könnte (Staufenbiel, 2023). In dieser Untersuchung wurden zusammen 130 Pferde aus den 13 Flächenbundesländern Deutschlands analysiert. Die Probanden stammten aus verschiedenen Rassen und Altersgruppen (2 bis 35 Jahre) und wurden sowohl sportlich als auch freizeitlich genutzt. Alle Tiere hatten Zugang zu Weiden. Die Messung der Spurenelemente Kupfer (Cu), Zink (Zn), Selen (Se), Eisen (Fe), Iod (I), Mangan (Mn), Molybdän (Mo), Bor (B), Chrom (Cr), Nickel (Ni), Silicium (Si), Zinn (Sn), Rubidium (Rb) und Vanadium (V) erfolgte mittels optischer Emissionsspektrometrie mit induktiv gekoppeltem Plasma (ICP-OES), während die Mengenelemente Calcium (Ca), Phosphor (P), Natrium (Na), Kalium (K), Magnesium (Mg), Chlor (Cl) und Schwefel (S) mit Hilfe der Massenspektrometrie und induktiv gekoppeltem Plasma (ICP-MS) bestimmt wurden. Die Analyse der Spurenelemente und Mengenelemente wurde anhand der spezifischen Funktionen dieser Mineralstoffe im Pferdeorganismus durchgeführt. Die erste Publikation dieser Arbeit befasste sich mit der Zinkkonzentration in Kot- und Blutproben von Pferden. Zink ist ein essentielles Spurenelement, das an zahlreichen Stoffwechselprozessen beteiligt ist. In dieser Studie konnte keine Korrelation zwischen den Zinkkonzentrationen in Kot- und Blutproben festgestellt werden. Jedoch zeigte sich eine Korrelation zwischen den verschiedenen Blutprobenarten (Serum, Plasma, EDTA-Blut). Zudem wurden erste Referenzwerte für die Zinkkonzentration in Kotproben ermittelt, die zwischen 29 und 413 mg/kg lagen. Diese Werte müssen jedoch unter Berücksichtigung der verschiedenen Limitationen, wie zum Beispiel der Variabilität in der Fütterung und der Haltung der Tiere, kritisch hinterfragt werden. In der zweiten Publikation wurde die Kupferkonzentration in Kot- und Blutproben untersucht. Kupfer ist ein weiteres essentielles Spurenelement, das unter anderem für die Kollagen- und Elastinbildung sowie für antioxidative Abwehrmechanismen eine wichtige Rolle spielt. Auch hier konnte keine Korrelation zwischen den Kupferkonzentrationen in Kot- und Blutproben nachgewiesen werden, jedoch eine Korrelation innerhalb der Blutprobenarten. In dieser Studie wurden keine Referenzwerte für die Kupferkonzentration in Kotproben ermittelt. Da diese Untersuchung unter den Bedingungen eines Feldexperiments durchgeführt wurde, müssen die Ergebnisse im Hinblick auf die verschiedenen Einflussfaktoren, wie die Haltungs- und Fütterungsbedingungen, die geographische Lage, das Alter und die Rasse der Tiere, mit Vorsicht interpretiert werden. Die Vielfalt dieser Faktoren schränkt die Generalisierbarkeit der Ergebnisse ein und zeigt, dass die Nutzung von Kotproben zur Bestimmung von Mengen- und Spurenelementkonzentrationen noch weiterer Forschung bedarf. Zusammenfassend lässt sich sagen, dass die Serologie nach wie vor ein wertvolles Diagnostikum in der Pferdemedizin darstellt, um den Mineralstoffstatus von Pferden zu bestimmen. Allerdings zeigt die vorliegende Arbeit, dass die Serologie nicht zwangsläufig die beste oder einzig geeignete Methode für die Bestimmung von Mengen- und Spurenelementen ist. Die Ergebnisse deuten darauf hin, dass eine ganzheitliche Herangehensweise, die verschiedene Analysemethoden kombiniert, der genaueren Bestimmung des Mineralstoffstatus eines Pferdes am besten dient. Die Kotprobenanalyse könnte in Zukunft eine wertvolle Ergänzung zur Blutuntersuchung darstellen, sofern weitere Studien und standardisierte Referenzwerte eine zuverlässige Interpretation ermöglichen. In zukünftigen Arbeiten wäre es ratsam, unter kontrollierten Bedingungen gezielte Fütterungsexperimente durchzuführen, um eine direkte Verbindung zwischen der Rationsanalyse und der Kotprobenuntersuchung herzustellen. Diese Untersuchungen könnten wichtige Grundlagen für die Etablierung verlässlicher Referenzwerte liefern.

The delivery of therapeutic nucleic acids into cells is the goal of gene therapy, which is still a challenge. Therefore, the focus of this work was to identify carriers capable of transfecting target cells with therapeutic plasmids in vivo in order to develop a platform technology for the treatment of cancer. The dendrimer poly(amidoamine) (PAMAM) and the peptide K16C and, based on these, various prototypes with different surface modifications were tested as carrier systems for the delivery of the so-called suicide gene encoding for the protein toxin saporin. To be successful as a carrier for transferring deoxyribonucleic acid (DNA) to target cells, a carrier must have a number of properties. For example, the carrier must form polyplexes that are stable in the blood, protect the DNA from degradation and, above all, be well tolerated by the body at the dose required for the therapeutic purpose. The DNA can only develop its potential to kill the cancer cell if the polyplex can circulate in the bloodstream long enough to reach its target. The experiments of this study clearly showed that the applied carrier molecules were able to protect the plasmid deoxyribonucleic acid (pDNA) from enzymatic digestion and were stable even after one hour of incubation in blood serum. In addition, the tested prototypes did not cause any measurable hemolysis at the doses planned for the in vivo experiments. However, the carrier PAMAM in particular showed a strong tendency to clump the erythrocytes. The influence of the carrier molecules and their polyplexes on blood coagulation cannot be denied. The retarding effect of the carrier PAMAM and its polyplex on the coagulation parameter prothrombin time (PT) was much stronger than that of the peptide K16C and its polyplex. Nevertheless, the values of all tested substances at a concentration of 1 μM were above the reference range. The effect on the partial thromboplastin time (PTT) parameter was striking. Almost all tested substances completely prevented coagulation starting with a concentration of 0.5 μM. The prototypes therefore carry the risk of an increased tendency to bleed after intravenous administration. Nevertheless, the starting point for further evaluation of the prototypes in in vivo toxicity studies was obtained. The no observed adverse effect level (NOAEL) is a threshold above which adverse effects or signs of toxicity occur. The aim of these studies was to determine an appropriate dose for the in vivo efficacy studies, in other words, to find the NOAEL for the prototypes. For the dendrimer-based prototypes and the peptidebased prototypes, the NOAEL was greater than the maximum dose administered. Consequently, all treatments were well tolerated with the exception of local inflammation at the injection site. The maximum intravenous dose administered was 45 μg pDNA for the dendrimer-based prototype and 15 μg pDNA for the peptide-based prototype. There was no evidence of elevated liver enzyme parameters and urea in the blood samples tested, which would be an indication of organ damage. The pathohistological examinations showed a clear activation of the spleen parenchyma. The suspicion that the treatments had activated the immune system was confirmed by testing the blood for specific antibodies against the carrier molecules using an enzyme-linked immunosorbent assay (ELISA). It was found that the amount of specific antibodies formed against the carrier molecules increased with increasing dose and number of injections. Once the maximum dose for the treatments had been determined and a comprehensive picture of the behavior of the prototypes in the blood had been obtained, the groundwork was laid for efficacy studies. A total of four peptide-based prototypes and four dendrimer-based prototypes were tested at two different doses for their tumor inhibitory properties in a colon cancer xenograft model. At a dose of 5 μg pDNA, the dendrimer-based carriers significantly reduced tumor growth. In particular, the prototype D5(SO1861)0.5 reduced the tumor volume by 75% and the prototype D5 by as much as 50%, resulting in prolonged survival in these groups compared to the vehicle control group. Follow-up experiments with a 3-fold higher dose of 15 μg pDNA were designed to confirm the results but did not yield the desired results. Nevertheless, further studies with other tumor mouse models will be useful to further investigate the tumor inhibitory effect of the dendrimer vectors. In contrast to the dendrimer-based prototypes, the overall performance of the peptide prototypes was less convincing. Although the peptide-based prototypes PP(SO1861)0.25 and PP + 30 μg SO1861 were able to significantly reduce tumor growth at a dose of 5 μg pDNA compared to the vehicle control group, but this did not lead to prolonged survival of the animals. Given that promising approaches with similar constructs have already been pursued in other projects, the developed prototypes should still be further investigated in other routes of administration and in other tumor models. It would also be worth investigating whether conjugation of SO1861 to the vector or co-administration with free SO1861 would be an improvement. Gene therapy offers the hope of taking a significant step closer to the ultimate goal of successfully treating currently incurable cancers, making further efforts in this project worthwhile.

Eine Aminosäure (AS) mit besonderer Relevanz für die Schweinefütterung ist Methionin (Met), welche in Form von DL-Met, L-Met oder DL-2-Hydroxy-4-(methylthio)buttersäure (DL-HMTBA) supplementiert werden kann. Es ist bekannt, dass diese Met-Supplemente den intestinalen Transport von Met sowie den Met-Metabolismus beeinflussen können. Die vorliegende Arbeit zielte darauf ab, die folgenden Hypothesen zu prüfen: Erstens, dass die Art des Met-Supplements nicht nur den Met-Transport, sondern auch den Transport weiterer AS beeinflusst und zweitens, dass sich verschiedene Met-Supplemente unterschiedlich auf das epitheliale Metabolom sowie die Expression von inflammatorischen Markern im porzinen Dünndarm auswirken. Im ersten Teil des Projektes wurde entweder eine Diät mit DL-Met, L-Met, DL-HMTBA oder keinem zusätzlichen Met-Supplement an junge Mastschweine verfüttert. Ihr Jejunum wurde verwendet, um den mukoserosalen Flux von [14C]-markiertem L-Glutamin, Glycin, LLeucin, L-Lysin, L-Met, L-Serin, L-Threonin, L-Tryptophan, L-Tyrosin und L-Valin mittels eines Ussing-Kammer-Modells zu untersuchen. Alle Fluxuntersuchungen wurde in An- und Abwesenheit von mukosalem Na+, sowie zwei mukosalen AS-Konzentrationen (50 μM/5 mM) durchgeführt. Weiterhin wurde eine Korrelationsanalyse der Na+-abhängigen AS-Fluxe angefertigt, sowie die cis-Inhibition des apikalen Transports durch mukosales L-Met untersucht. Für letzteres wurde ausschließlich eine DL-Met-Vorfütterung eingesetzt. Um funktionelle Unterschiede zwischen der vorliegenden und einer vorangegangenen Studie zu untersuchen, wurde die jejunale Genexpression neutraler apikaler AS-Transporter (SLC1A5, SLC6A19, SLC6A20, SLC6A14) sowie verschiedener Entzündungsmarker (NLR family pyrin domain containing 3 (NLRP3), Caspase1 (CASP1), Interleukin (IL)1β, IL8, IL18, Tumornekrosefaktor α, Transforming growth factor β (TGFβ)) und des Angiotensin-Konversionsenzyms II (ACE2) zwischen beiden Studien verglichen. Die Ergebnisse zeigten eine deutliche Na+-Abhängigkeit fast aller AS-Fluxe mit Ausnahme von Lysin und Tryptophan bei 5 mM AS-Konzentration. Diese Na+-abhängigen Fluxe korrelierten vielfach untereinander. Ausnahmen bildeten Glycin mit nur wenigen und Tryptophan mit keiner Korrelation zu weiteren AS. Die apikale Aufnahme aller AS außer Glycin und Lysin war einer cis-Inhibition durch mukosales Met unterworfen. Die vergleichenden Untersuchungen der Genexpression zeigte eine erhöhte Expression von SLC6A19 (B0AT1) und eine niedrigere Expression von SLC6A14 (ABT0,+) in der vorliegenden vs. der Vorgängerstudie. Zusätzlich konnte eine erhöhte Expression aller Entzündungsmarker außer NLRP3 und IL18 in der Vorgängerstudie nachgewiesen werden. Die Expression des Angiotensin-Konversionsenzyms II unterschied sich nicht signifikant zwischen den beiden Studien.

Im zweiten Teil des Projektes wurde das Metabolom des Duodenums, des proximalen und mittleren Jejunums sowie des Ileums von Schweinen mittels Ultrahochleistungsflüssigkeitschromatographie und Tandemmassenspektrometrie analysiert. Die Tiere erhielten entweder DL-Met, L-Met oder DL-HMTBA als Futtersupplemente. Weiterhin wurde dieses Gewebe verwendet, um den Einfluss der Supplemente auf die Expression verschiedener Entzündungsmarker (NLRP3, CASP1, IL1β, IL8, IL18, TGFβ) zu untersuchen. Die Supplemente hatten keine Auswirkung auf das globale intestinale Metabolom, allerdings zeigte eine Stoffwechselweg-Analyse einen signifikanten Effekt auf Stoffwechselwege des Lipidmetabolismus. So reduzierte L-Met die relative Konzentration von mehrfach ungesättigten Fettsäuren im Gewebe. Weiterhin waren sekundäre Gallensäuren im Jejunum der L-Met- und im Ileum in der DL-HMTBA-Gruppe angereichert. Im distalen Dünndarm zeigte sich eine signifikante Anreicherung von Monohydroxy-Fettsäuren sowie ein statistischer Trend in Richtung Anreicherung von Sphingosinen. Hingegen hatten die Supplemente eine weniger deutliche Auswirkung auf Metabolite, die mit dem antioxidativen System und dem inflammatorischen Status in Verbindung stehen. So führte insbesondere L- und DL-Met-Supplementierung zu einer Anreicherung einzelner oxidierter Met-Metabolite im Gewebe. Zusätzlich wurde ein statistischer Trend der Anreicherung von Metaboliten im Tocopherol- und im Histidin-Metabolismus beobachtet. Hierbei ging eine DL-Met- und DL-HMTBA-Supplementierung mit einem relativen jejunalen Anstieg von β- und γ-Tocopherolen sowie von α-Tocotrienolen im Gewebe einher. Zusätzlich waren Histidinmetabolite in der DL-Met-Gruppe angereichert. Die Expressionslevel der Entzündungsmarker unterschieden sich in dieser Studie nicht zwischen den Met-Supplementen. Zusammenfassend hatte die Met-Supplementierung in dieser Arbeit keine Auswirkung auf den intestinalen AS-Transport. Allgemein unterstützen die Daten jedoch das gegenwärtige Konzept des intestinalen neutralen AS-Transportes, welches B0AT1 eine prominente Rolle zuschreibt. Im intestinalen Metabolom beeinflussten die Met-Supplemente verschiedene Lipid-Stoffwechselwege, die Expression von Entzündungsmarkern unterschied sich in der vorliegenden Studie allerdings nicht zwischen den Met-Supplementen. Jedoch sprechen die Expressionsunterschiede der Entzündungsmarker zwischen den Studien dafür, dass die Effekte von Met-Supplementen auf den AS-Transport durch sekundäre Faktoren wie beispielsweise eine Entzündung beeinflusst werden können. Die vorliegende Arbeit zeigt praxisrelevante Aspekte der Met-Supplementierung auf und legt damit die Basis für zukünftige Studien zur detaillierten Charakterisierung des Einflusses externer Faktoren auf die Interaktion zwischen Met-Supplementen und dem AS-Transport sowie der Regulationsmechanismen von Met-Supplementierung im intestinalen Lipidmetabolismus.

The development of quantum technologies, such as quantum simulators, promises significant advancements in the study of complex systems, including many-body physics. One promising approach for realizing a quantum simulator is to use nitrogen-vacancy (NV) centers in diamond. A hybrid system, in which an NV center serves as a quantum probe for initialization, manipulation and readout, while nuclear spin arrays on the diamond surface function as qubits, presents a potential direction for quantum simulator development.

NV centers are widely used as quantum sensors due to their unique properties. However, their high sensitivity, while advantageous, also introduces challenges in the fabrication and stability of a diamond-based quantum simulator. Achieving a functional system requires careful consideration of structural complexity, material interactions, and environmental conditions.

This PhD thesis explores and addresses the challenges encountered during the fabrication process of an NV-based quantum simulator. From hyperfine interactions to limitations imposed by experimental equipment, this study provides a comprehensive overview of the complexities involved. Additionally, it presents potential strategies for mitigating these challenges, contributing to the ongoing development of scalable and reliable quantum simulation platforms.

A diamond-based quantum simulator offers promising advantages, including room-temperature operation, non-destructive measurements, and the potential for long-lived quantum memories. Advances in diamond growth, surface engineering, and quantum control techniques are steadily improving the stability and coherence of NV centers, bringing this technology closer to practical realization. While large-scale NV-based quantum simulators have yet to be implemented, this work represents an important step toward their feasibility, identifying key material and control challenges that must be addressed to unlock their full potential.

Background: Studies in mice infected with gastrointestinal (GI) nematodes, particularly Heligmosomoides polygyrus bakeri (H. bakeri), provide critical insights into the immune factors that govern resistance to infection. Resistance to H. bakeri is primarily mediated by high levels of GATA-3+ CD4+ Th2 cells in mesenteric lymph nodes (MLN). Two mouse strains are commonly studied: BALB/c mice, which efficiently clear the infection within weeks, and C57BL/6 mice, which are more susceptible, often carrying the infection for months, making them a useful model for chronic infection research. Age impacts resistance in BALB/c mice, with older mice showing reduced immunity due to slower effector cell migration to the infection site. This study explores whether resistance to H. bakeri infection is influenced by both genetic and age-related factors affecting effector cell recruitment to the infected gut. Additionally, the research examines the role of liver-draining lymph nodes (celiac lymph node; CLN, portal lymph node, PLN) in immune response modulation and the interplay between the liver and gut during infection, analyzing how these affect the liver metabolic microenvironment and shape immune response and infection outcome.

Aims: 1. To determine whether genotype and age influence resistance to H. bakeri infection 2. To investigate how these factors modulate the speed and efficiency of effector cell recruitment 3. To elucidate the role of liver-draining lymph nodes (LLNs) in the differentiation of classical Th2 and Th2/1 hybrid cells 4. To explore the potential impact of co-drainage between the MLN and LLNs on immune responses 5. To explore the interaction between liver and T cells during H. bakeri infection

Results: We show that in resistant BALB/c mice, rapid Th2 cell recruitment to the gut, driven by CCR9 expression and specific dendritic cells, effectively limits early H. bakeri larval development. In contrast, delayed Th2 responses in susceptible C57BL/6 mice allow larvae to mature into adult worms, while aging BALB/c mice also experience reduced Th2 homing, diminishing their resistance. Additionally, liver-draining lymph nodes contribute to immunity byexpanding Th2 cells (CLN) and supporting high-affinity IgG1 antibody production (PLN). Liver-resident T cells produce high levels of IL-5, IL-4, and IL-13 in a glucose-rich environment, which enhances their immune functionality.

Conclusion: This study demonstrates that BALB/c mice resist H. bakeri infection more effectively than C57BL/6 mice due to enhanced CCR9 expression and swift Th2 cell recruitment to the gut. In older BALB/c mice, reduced ALDH activity and delayed Th2 recruitment weaken resistance. Furthermore, despite limited Th2 activity, PLN compensates with strong TFH bias, forming more GCs that produce high-affinity antibodies. The liver also plays a key immune role by sustaining Th2/1 responses through IFN-γ, CXCR3, and metabolic adaptations. This highlights the liver’s potential as a target for optimizing immune response modulation in intestinal helminth infections.

The Periodic Event Scheduling Problem (PESP) serves as the foundational framework for optimizing periodic timetables in public transport. We here present advances in the theoretical understanding of PESP and its underlying geometries, as well as novel ways to model and optimize timetabling with integrated infrastructure aspects in practice. First, having formulated PESP as a mixed-integer program, we study the geometric structure of the problem. In the periodic timetable space we find a collection of polytropes, tropical polytopes that are also traditionally convex, wrapped onto a torus. Instead, in the space of cycle offsets, which are auxiliary integer variables, we find a special zonotope, of high combinatorial interest. We establish connections between these two geometries, and employ these newfound insights to develop a novel local improvement heuristic for PESP, Tropical Neighbourhood Search (\tns{}), which we extensively test and evaluate with excellent computational results. In the second half of the dissertation, we focus on the challenge of properly integrating infrastructure constraints with periodic timetabling. We construct novel MIP-based modelling strategies, relevant cutting planes, and other approaches using cycle orders and perfect matchings, to ensure that found solutions are safely operable on the available infrastructure, while also optimizing the assignment of vehicles to ground resources, making full use of previously untapped track capacity. The viability and practical relevance of our models, Infrastructure-Aware PESP and its extensions, is showcased over multiple case studies on real-world public transport networks.

Applying electron spin resonance (ESR) dating to sedimentary quartz poses a significant challenge due to the difficulty in bleaching the signals. The aim of this PhD thesis is to contribute to the improvement of a reliable ESR dating technique by quantifying and correcting ESR residual signals caused by insufficient bleaching prior to sediment deposition. Particularly within the realm of archaeology, there is a pressing need for a geochronological method capable of dating quartz and other materials well beyond the constraints of the already-established dating methods, e.g. luminescence dating. The initial study investigates the reliability of quartz ESR dating, focusing on the Ti centre. Loess from the Luochuan site on the Chinese Loess Plateau with a known reference age was used. By the use of the single-aliquot regenerative dose (SAR) protocol the equivalent dose (De) was determined for a sequence of five samples. For the two youngest samples the ESR ages were higher than the anticipated ages, indicating an incomplete signal resetting before sedimentation, whereas the oldest samples showed an approx. 20 % underestimation, indicating thermal signal loss with time. In the latter case, the apparent age could be successfully corrected for the signal loss. For the remaining samples the corrected ages were in satisfactory agreement with the expected ages. The second study focuses on the ESR residual signals caused by incomplete signal resetting before sedimentation. For this purpose, a series of early Holocene fluvial sediments with known optically stimulated luminescence (OSL) ages were analysed. Applying the SAR protocol to determine the residual doses for both the aluminium (Al) and titanium (Ti) impurity centres. It was revealed, that all investigated samples carried a considerable residual dose. To rule out methodological problems, the SAR protocol was tested for accuracy. The test revealed that the signal originating from the lithium-compensated Ti centre (Ti-Li) and a signal which originates from both the Ti-Li and the hydrogen-compensated Ti centre (Ti-H), referred to as Ti-mix, showed good results whereas the signal from the Al centre and the Ti-H signal showed that the heating and annealing steps throughout the process alter the samples ESR characteristics rendering the SAR protocol inappropriate to use in this two cases. Our findings suggest the necessity of conducting more direct comparisons between luminescence and ESR equivalent doses, with the subtraction of residual doses obtained from the difference being essential for obtaining reliable ESR ages if needed. This procedure was not used in previous work, as it was either assumed that the Ti centres were all completely bleached or, as long as the determined ages of the individual centres matched, complete bleaching was assumed. In order to apply the knowledge gained in the course of this work, the transition age from the Early Stone Age (ESA) to the Middle Stone Age (MSA) in archaeological sites near the Victoria Falls, Zambia, was dated since this technological change in stone tool making has been poorly understood by now. The combined advantages of both, single-grain OSL and single aliquot ESR dating on quartz, the good bleachability of the signals and the extended age range was used. For the same set of young samples, derived from sandy deposits bearing Stone tools, we applied both methods and found large differences in OSL and ESR equivalent doses. We estimated the mean ESR residual age by discerning the difference between OSL ages and the apparent ESR ages. Specifically emphasizing the SAR protocol, we successfully determined the mean ESR residual age for the Ti and Al centre, encompassing the non-bleachable signal component for the latter. We successfully determined the average residual age of ESR for both Ti and Al centre, incorporating the non-bleachable signal component for the latter. The size of these residual ages, ranging from 209 ± 13 ka to 268 ± 39 ka and 695 ± 23 ka to 742 ± 118 ka for the Ti centre and Al centre, which cannot be understated and must be taken into consideration. Consequently, the apparent ESR ages were adjusted by subtracting the residual age. By this we were able to get persistent residual subtracted ESR ages, which are within a 2- uncertainty when compared to the OSL ages. Eventually, we successfully pinpointed the end of the Early Stone Age at 590 ± 86 ka, establishing a maximum age for the transition to the Middle Stone Age in this specific region of south-central Africa. It should be noted that the residual ages depend on the respective geological setting, the climate and the deposition history of the sediments. Factors such as the transport route, the efficiency of bleaching by sunlight and possible rearrangements have a significant influence on whether a sediment grain was completely bleached before deposition or whether a residual signal or a residual age remains. In order to recognize and evaluate such influences, it is necessary to examine the deposition environment in detail, for example by analysing the grain size distribution, sediment structures or the composition of the sediment. Only through such sedimentological and geomorphological contextualization can ages obtained in this way be reliably interpreted. Nevertheless, we think that this approach gives a good example for the combined use of two related dating methods by carefully investigate the signal properties to unveil ESR residual signals. The age we published adds to the sparsely dated ESA/MSA transition in this geographic region.

Given the alarming increase in AKI incidence in general, which was further exacerbated during the COVID-19 pandemic, there is an urgent need to invest more effort in improving the diagnosis and treatment approaches in patients with AKI. The drawbacks in the recognition of AKI combined with ineffective KRT have far-reaching consequences - not only for individuals but also for social and medical systems. A selection of critical factors that could improve the outcome of patients with AKI is described in this habilitation thesis. Our research findings showed that the incidence of AKI detected by creatinine changes is much higher than its administrative reporting, even in the context of university hospitals in a high-income country such as Germany. Since AKI leads to significantly higher mortality, even in patients whose the diagnosis was not properly documented, the implementation of an automated analysis of clinical data and amplification of clinical decision support algorithms is highly recommended as this could allow for the earlier detection of AKI and might prevent the development of severe kidney injury that requires KRT. One of the most important issues during CKRT is the anticoagulation protocol, RCA has become the standard of care. However, the variety of RCA protocols still requires optimization. We further outlined that the first crucial step in improvement of the RCA protocol for CKRT is its robust validation in terms of safety and efficacy before its broader implementation in clinical routine. This approach will allow caregivers to adopt possible recommendations and adjust the protocol according to local demands and structures, which may improve the safety for the treated patients treated. Since the pfCa concentration has historically served as a valid marker of the anticoagulation efficacy of RCA, close monitoring of pfCa during CKRT has been recommended. We showed that the association of the pfCa with anticoagulation efficacy during RCA-CKRT might be weaker than expected if a protocol with a fixed and high citrate dose is applied. In addition, we highlight the potential of less intensive pfCa monitoring during RCA-CKRT, which may ultimately save staff and material resources without jeopardizing the treatment efficacy. The metabolic complications of RCA were supposed to be the most important drawback of this anticoagulation approach for CKRT, with citrate accumulation being the most severe one. The human body´s ability to metabolize citrate is limited and compromised during shock and other hypoperfusion states, leading to a higher incidence of citrate accumulation during RCA. However, for some time there were no robust data justifying the strict contraindication of RCA during CKRT in patients with hyperlactatemia. In a previous study, we showed that the incidence of citrate accumulation is relatively low even if RCA-CKRT is applied in the unselected cohort of critically ill patients. Furthermore, in the secondary analysis, we found that even in patients with initially severe hyperlactatemia, the frequency of citrate accumulation was still acceptable and patients with significant lactate clearance had a negligible risk for citrate accumulation, even despite initially elevated lactate concentrations. On the other hand, critically ill patients with initially low lactate levels but increasing lactate concentration as a marker of multiorgan disfunction showed a significantly higher incidence of citrate accumulation. Hence, the collective findings indicate that severe hyperlactatemia should not be considered a strict contraindication for RCA-CKRT, whereas patients with insufficient lactate clearance are at risk for developing citrate accumulation. Like many other ICUs across the world during the COVID-19 pandemic, we experienced a significant increase in patients admitted with AKI requiring CKRT. Significant concerns were raised about the optimal anticoagulation approach during CKRT in critically ill COVID-19 patients. In our study, we reported that the efficacy of RCA during CKRT in COVID-19 patients is comparable – and at least non-inferior – to that found in non-COVID-19 patients. However, we also showed that the incidence of metabolic complications during RCA-CKRT in COVID- 19 patients has a different pattern and might be explained by reduced filter patency and thus by an increased systemic citrate load during the CKRT. Based on these findings, we recommend that special attention should be paid to patients with a circuit life of over 48 hours. Another promising therapeutic approach for critically ill COVID-19 patients was the application of a cytokine adsorber that could be mounted on the CKRT circuit. In our prospective randomized pilot study, we investigated the impact of cytokine adsorption by CytoSorb on the resolution of vasoplegic shock and the course of the disease. Our data showed that CytoSorb adsorption did not improve the resolution of shock compared with patients treated with standard therapy. In addition, there was no significant differences in the mortality rates or catecholamine requirements, or the kinetics of the inflammatory parameters (e.g., IL-6 and CRP) between the groups. While further studies are warranted to examine the clinical effect of cytokine elimination in COVID-19 patients, RCA-CKRT was shown to be a reliable and effective matrix for the future application of other adsorptive devices and filters of any type. In summary, we studied important diagnostic and therapeutic factors that significantly influence the expected short- and long-term outcomes of patients with AKI. An optimal and complex approach to the medical care of patients with AKI is important to reduce the high burden of this common condition on the individual patient in particular, and the healthcare system in general.

„Sprachalchemisten“, „Barock-„ oder „Beatpoeten“, „DDR-Avantgarde“, „Kollaborateure unter der Maske der französischen Theorie“: Bereits diese schillernden Zitate aus Feuilleton und Forschung lassen erahnen, welche Mythen und Kontroversen sich bis heute um jene inoffizielle Lyrikszene ranken, die sich in der Spätphase der DDR im Ostberliner Stadtteil Prenzlauer Berg herausbildete. Nicht erst seit der Stasi-Affäre um Sascha Anderson 1991 ist rege darüber diskutiert worden, ob es sich bei der „Prenzlauer-Berg-Connection“ überhaupt um eine klar abgrenzbare Gemeinschaft oder nicht doch eher um eine konstruierte Zusammenschau chaotischer Einzelkämpfer handelte.

Die Studie von Lukas Nils Regeler verfolgt die These, dass sich die Gemeinschaftsbildung im Prenzlauer Berg der 1980er Jahre besonders dort gut nachvollziehen lässt, wo die Autor:innen als Leser:innen auftreten, indem sie etwa Theorieelemente, Schreibweisen und Motive aus literarischen und philosophischen Strömungen aufgreifen und produktiv machen, die im offiziellen Kulturbetrieb der DDR wenig Platz hatten. Anhand der emphatischen Bezugnahmen von Autor:innen wie Bert Papenfuß, Elke Erb, Johannes Jansen, Leonhard Lorek, Raja Lubinetzki oder Rainer Schedlinski auf die Literaturen der Frühen Neuzeit, die historischen Avantgarden, die US-amerikanische Beatgeneration und die Theorien des französischen Poststrukturalismus werden so Ein- und Ausschlussmechanismen der Gemeinschaftsbildung greifbar. Damit leistet die Untersuchung auch einen Beitrag zu einer Literaturgeschichte der DDR, die weniger in Generationen und Schulen argumentiert, sondern vielmehr transtemporale und internationale Verflechtungen in den Blick nimmt.

T-cell-based immunotherapies aim to treat various malignancies by targeting intracellular protein-derived peptides processed by the proteasome and presented on MHC class I molecules. A critical step in the development of these therapies is the accurate selection of target MHC ligands. This selection is often guided by computational prediction algorithms, particularly in the context of vaccine design, rather than experimental validation of antigen presentation. However, these algorithms frequently fail to accurately reflect the complexity of natural antigen processing and presentation, potentially leading to false-positive results and misdirected therapeutic strategies. To systematically evaluate these predictions, this thesis employs a COS-7 monoallelic cell system in liason with immunopeptidomics to screen 150 combinations of individual neoantigens/tumor-associated antigens and HLA alleles. Surprisingly, only 21.6% of predicted neoepitopes were experimentally validated, revealing a 78% false-positive rate of computational prediction algorithms. Similarly, these computational tools are frequently used to establish links between public neoepitope presentation and downstream biological effects including immune evasion through HLA loss of heterozygosity (HLA-LOH). However, this link was also disrupted in 77% of HLA-LOH cases, where the predicted neoepitopes showed no evidence of presentation on the corresponding HLA alleles, thereby challenging the assumption that HLA-LOH is mainly driven by public neoantigen presentation. Importantly, we identified 24 novel public neoepitopes across 11 HLA alleles, derived from recurrent driver mutations (e.g., TP53, EGFR) and resistance-related alterations (e.g., CTNNB1, ESR1), alongside 13 novel tumor-associated epitopes (e.g., derived from MAGE-A4, PRAME, CT83, NY-ESO-1) across 4 common HLA alleles. Two epitopes, KVDELAHFL (MAGE-A4) and KVLEHVVRV (MAGE-A4), were each presented on two common HLA alleles, offering a promising strategy to broaden patient eligibility for TCR-based therapies. Furthermore, when testing sequences used for personalized mRNA neoepitope vaccines, we observed that clinical responses were independent of the presentation status of the neoepitopes, highlighting the risk of measuring false-positive responses during T-cell monitoring. Even a presumably neoepitope-specific TCR clone from a neoantigen vaccination study could not be linked to a successfully presented neoepitope. In contrast, we observed cross-reactivity of the TCR’s targets with a CMV-specific epitope as a potential explanation for the T-cell response measured during T-cell monitoring. Overall, these data challenge current assumptions about neoantigen responses, immune evasion, and the reliability of computational predictions.

This habilitation thesis focuses on specific questions within psychiatric health services research, particularly regarding day clinic treatment offerings. It begins with the first survey conducted in the German-speaking world on disorder-specific, day clinic, and inpatient treatment options for individuals with borderline personality disorder (BPD). The findings reveal a significant undersupply of care, characterized by long waiting times and a very high patient-to-treatment-place ratio for DBT (Dialectical Behavior Therapy), clearly indicating that existing services do not meet actual demand.

Building on this, a specialized DBT day clinic in a Berlin psychiatric care region was evaluated. This clinic aimed to address the identified treatment gap. The evaluation showed, for the first time, statistically significant to highly significant improvements in BPD-specific symptoms. The study also systematically examined negative effects of the DBT treatment – a first for a day clinic setting – by identifying which negative effects patients subjectively experienced. Additionally, the research sought to identify patient-level predictors for poor treatment response, with the goal of informing future therapeutic developments for BPD.

Subsequent publications stemmed from this methodological evaluation approach, now applied to a different therapeutic concept: a transdiagnostic (i.e., not disorder-specific) treatment in a day clinic for a more heterogeneous psychiatric patient group. These studies also demonstrated high treatment effectiveness, not only in symptom reduction but also in improvements in patients’ subjective quality of life. Notably, the negative effects of the transdiagnostic ACT (Acceptance and Commitment Therapy) approach were found to be lower compared to other clinical populations.

The ACT day clinic study was conducted during the COVID-19 pandemic, thus reflecting the challenges of delivering mental health care during a particularly vulnerable period.

In summary, the thesis examines the real-world implementation of psychiatric care structures from a health services research perspective, with a focus on day clinics. It scientifically documents the benefits and possible downsides of selected therapeutic methods and their sometimes surprising treatment outcomes. The findings are based on real, unfiltered data from two Berlin psychiatric care regions and provide a representative snapshot of mental health service delivery at the time of study. These results may contribute to the ongoing development of day clinic models to improve mental health care delivery.

The two day clinics investigated serve as examples of different models within the evolving landscape of psychiatric care: one being a highly specialized, disorder-specific DBT program, the other a broad, transdiagnostic ACT approach. Both reflect recent trends toward more outpatient-oriented treatment structures in psychiatry.

Heute weitgehend in Vergessenheit geraten, war Johann Wilhelm Überfeld um 1700 ein Mann, der polarisierte: Der gelernte Kaufmann inszenierte sich als religiöser Virtuose mit unmittelbarem Zugang zu göttlicher Weisheit. Vom niederländischen Leiden aus schickte er unzählige Unterweisungsschreiben an Bewunderer und Interessierte quer durch das protestantische Mitteleuropa. Theologische Widersacher erkannten in ihm das Oberhaupt einer gefährlichen außerkirchlichen Gruppierung – der Gemeinschaft der Engelsbrüder. Lennart Gard befasst sich in seiner Studie erstmals eingehend mit Überfeld und den Menschen, die sich mit ihm austauschten und auseinandersetzten. Auf Basis umfassender Quellenbestände geht er exemplarisch der Frage nach, wie religiöses Miteinander jenseits kirchlicher Strukturen in der Frühen Neuzeit funktionierte und gedeutet wurde. Die Untersuchung beschäftigt sich dazu mit Vorstellungen, Sozialbeziehungen, Lebenswelten und Erinnerungskulturen religiöser Menschen des 17. und 18. Jahrhunderts. Zugleich wird verdeutlicht, wie in jener Zeit polemische Gemeinschaftsbilder mit Auswirkungen bis in die Gegenwart entstanden. Als Kultur- und Sozialgeschichte religiöser Kommunikation vermittelt die Studie neue Perspektiven auf die Vielfalt des frühneuzeitlichen Protestantismus und deren historische und historiographische Wahrnehmung.

Aging is a complex biological process associated with systemic and cellular dysfunctions. Both fasting (i.e., time-restricted feeding) and dietary protein restriction (PR) are among the most promising interventions to promote healthy aging. Since the two paradigms are hardly compatible, it has remained unclear whether they may exert synergistic effects. However, recent studies have shown that the endogenous polyamine spermidine increases during fasting in both the fruit fly, Drosophila, and humans. In my dissertation, I therefore treated Drosophila with a combination of dietary spermidine supplementation (SPD) and PR to assess whether their effects are additive or synergistic. My observations confirmed that both interventions act through orthogonal mechanisms, which encourages future clinical studies in this direction. The Drosophila study included behavioral analyses (lifespan, locomotion, and fecundity) combined with polyamine quantification and proteome profiling. Both SPD and PR alone promoted healthspan and lifespan in flies, while their combination provided additional benefits — including extended lifespan, improved locomotion, and prolonged fecundity in aging flies. SPD (but not PR) increased putrescine and spermidine levels in PR-fed flies and reprogrammed the proteome toward specific metabolic pathways — including mitochondrial metabolism, autophagy, and hypusination. Hypusination is a posttranslational modification of the eukaryotic initiation factor 5A (eIF5A), in which spermidine donates an aminobutyl group to a specific lysine residue, forming hypusine (Nε-[4-amino-2-hydroxybutyl]-lysine). ____________________________________________________________________________________________________ In the second part of this work (ImmuneAge trial in human participants), we investigated the role of SPD in immune rejuvenation and conducted a comprehensive analysis of polyamine biokinetics in blood fractions (plasma, serum, and cellular components) in collaboration Charité – Universitätsmedizin Berlin, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Leibniz Institute for Analytical Sciences – ISAS – e.V., and The Longevity Labs GmbH (TLL). The ImmuneAge Trial used a multi-parameter molecular profiling approach, including ELISA for inflammatory markers, LC-MS for polyamine quantification, proteomics, western blot analysis for autophagy and hypusination markers, and flow cytometry to evaluate immune responses. We showed that a 20-day SPD significantly enhanced autophagy and hypusination in peripheral blood mononuclear cells (PBMCs), particularly in younger participants (20–40 years), with similar trends observed in older individuals (60–90 years). These effects correlated with SPD’s strong ability to counteract the age-related decline of spermidine levels in PBMCs. Moreover, SPD reduced inflammaging and improved aspects of both innate and adaptive immune responses to the SARS-CoV-2 spike peptide, with stronger effects in younger participants. Plasma proteomics revealed that SPD strengthened the immune system, lowered thrombosis risk, and reduced inflammation in older participants, while in younger participants, it improved lipid metabolism and triggered changes considered cardioprotective.

Driving fundamentally challenges the established equilibrium paradigms of interacting quantum many-body systems. Quantum spin systems exposed to periodic, quasiperiodic and direct-current driving can enter non-equilibrium phases of matter with no equilibrium analog. A striking example is a Floquet time crystal, a phase of matter stabilized by periodic driving, that breaks time-translation symmetry and is thus at odds with thermal equilibrium. The time crystal owes its robustness against perturbations to the interactions between the particles. It is thus a representative case that highlights the important role of interactions in the presence of driving.

This thesis employs the quantum Ising model as a platform to explore driven many-body dynamics. First, we study the dynamics of correlation functions of the periodically driven quantum Ising model. In the open chain, periodic driving stabilizes Floquet Majorana zero modes (MZMs) and Majorana π modes (MPMs) at its boundaries, implying characteristic level pairings throughout the many-body spectrum. We show that the level pairing statistics differ markedly between MZMs and MPMs in the presence of random symmetry-breaking fields, with implications for the boundary spin correlations. In the coexisting regime of MZMs and MPMs, we construct a composite boundary mode as their operator product. We analyze the resilience of the composite mode against integrability-breaking perturbations, surpassing the stability of the individual boundary modes. Next, we apply a quasiperiodic Fibonacci drive to the quantum Ising chain. The boundaries can host Majorana golden-ratio modes (MGMs) unique to the quasiperiodic setting. We map out the dynamic phase diagram which contains self-similar structures under time evolution. Returning to periodic drives, we revisit the relation of the Floquet time crystal to the spectral π pairings of the many-body Floquet operator. Our work shows that the level pairing statistics provides analytical expressions for the temporal spin correlations in Floquet time crystals.

Finally, we turn to magnetic impurities in superconductors. We treat the spins of a Yu-Shiba- Rusinov dimer fully quantum in a zero-bandwidth approximation, accounting for the complex interplay of screening, superconducting correlations, magnetic anisotropies and substrate-mediated interactions. The dimer shows rich phases and excitation spectra which underscore the role of interactions between spins under direct-current driving in a solid-state platform.

This dissertation explores how macroeconomic policy and conditions interact with expectations, institutional constraints, and country, as well as household heterogeneity. In four chapters, I study how monetary policy reaches the public via the media, how fiscal rules shape governments' ability to respond to shocks, and how we can track changes in income inequality in real time. Chapter 1 examines how media coverage of the European Central Bank (ECB) shapes consumer inflation expectations. The media act as a key intermediary between central banks and the public; I investigate which monetary policy topics in media reporting matter most to consumers. I identify seven core topics - interest rates, inflation, economic growth, purchase programs, uncertainty, fiscal policy, and financial markets - and measure their prominence in leading economic newspapers in the euro area’s four largest economies using Latent Semantic Indexing with factor rotation. To isolate the impact of topic-specific coverage, I construct media topic shifts around ECB press conferences in an event-study framework and estimate their effect using local projections. The results suggest that media coverage significantly influences inflation expectations: discussions on inflation and economic growth raise expectations, while talk about the financial topic dampens them. Consumers respond more strongly to the media's interpretation of ECB messages than to the messages themselves. Furthermore, the media generally reinforce ECB messaging, with the exception of the fiscal topic, where consumer expectations move in opposing directions depending on the source. These findings offer new insights into how monetary policy (communication) is filtered through the media and received by the public. Chapter 2, co-authored with Vegard H. Larsen and Nicolò Maffei-Faccioli, studies how ECB-related inflation news affect consumer inflation expectations heterogeneously across the four largest euro area countries. Using Latent Dirichlet Allocation, we measure the intensity of inflation coverage in the national media and estimate its effects in a Structural Vector Autoregressive model. We find that German and Italian consumers respond significantly to ECB inflation news, while no clear effect emerges for Spain and France. These results point to substantial cross-country heterogeneity in how central bank communication is received, highlighting the importance of national media in shaping policy transmission in a diverse monetary union. Chapter 3, joint with Christoph Große-Steffen and Malte Rieth, examines how fiscal rules affect macroeconomic stabilization in response to exogenous shocks. Using the unpredictability of natural disasters in an instrumental-variable approach, we construct a shock measure that is exogenous and comparable across countries. We combine the resulting shock series with quarterly macroeconomic data for 89 countries over nearly fifty years in a dynamic panel model. The results suggest that countries with fiscal rules absorb shocks better, with stronger recovery of GDP and private demand. These effects are linked to more expansionary fiscal policy and depend on available fiscal space, suggesting that rules can enhance countercyclical capacity. We further explore the role of rule design in a sovereign default model, focusing on the interplay between rule tightness and flexibility. The model shows that tight fiscal rules with escape clauses can support countercyclical responses and generate welfare gains, even under market discipline. Overall, our findings offer new evidence that well-designed fiscal rules can enhance resilience to economic shocks rather than constrain the policy response. Chapter 4, co-authored with Nina Maria Brehl and Geraldine Dany-Knedlik, examines whether macroeconomic developments shape the labor income distribution. Accurate and timely data on income dynamics are essential for informed policy responses, yet such information is typically published only annually and with substantial delays. We propose a method to nowcast the income distribution using dynamic factor models that combine high-frequency macroeconomic indicators with low-frequency household survey data from the German Socio-Economic Panel. A pseudo-real time evaluation shows that incorporating macroeconomic signals and inter-decile dynamics substantially improves forecast accuracy over a univariate benchmark - particularly for the middle and lower parts of the distribution. We apply the best-performing model to project income growth through 2024 and estimate inequality under the assumption of a generalized Pareto distribution. The results highlight a heterogeneous response of different income groups to macroeconomic shifts and show that inequality in Germany has likely risen in the aftermath of the European energy crisis. Our approach offers a practical framework for real-time monitoring of distributional developments.

Humans are remarkably fast at processing scenes and making decisions based on the information they contain. Within a few hundred milliseconds of viewing a scene, our brain can extract the most important information through a hierarchical cascade starting with perceptual attributes (color, edges, etc.) and ending with abstract properties (category, relationship between objects, etc.), eventually supporting decision-making. Despite the central role of scene processing, many aspects of how it unfolds in the brain remain poorly understood. In particular, the intermediate stages linking perceptual and abstract scene understanding, i.e., mid-level feature processing, are largely unresolved. Moreover, the link between neural activity and behavior, i.e., when, where and what kind of scene information arising in the brain influences decision-making, remains unclear. This thesis addresses these gaps through three studies implementing empirical and computational methods. In Study 1, we used a novel stimulus set to reveal that various mid-level features of scenes are processed in humans between ∼100 ms and ∼250 ms after stimulus onset, bridging low- and high-level feature representations, and with a temporal hierarchy that is mirrored by convolutional neural networks (CNNs). In Study 2, we showed that neural representations of scenes are suitably formatted for behavioral readout of scene naturalness between ∼100 ms and ∼200 ms, i.e., in the intermediate processing stages, and that intermediate CNN layers best correlated with the neural representations in this time-window, suggesting that mid-level features underlie behaviorally-relevant representations. In Study 3, we showed that neural representations of scenes are suitably formatted for behavioral readout of scene naturalness in the early visual cortex and in the object-selective high-level cortex, and that intermediate CNN layers best explain this brain-behavior relationship, indicating that behaviorally-relevant representations in these areas are driven by mid-level features. Taken together, the studies included in this thesis revealed the timing, spatial localization, and behavioral relevance of mid-level feature representations in scene processing, contributing to a better understanding of how the human brain extracts information from the surrounding world.