The notion of modeling complex physical systems using randomness goes back to the beginnings of statistical mechanics. Since then, randomized physical systems have been a subject of study from many-body physics to quantum information. In this thesis, we will examine random quantum systems in different contexts.

To start, we discuss the emergence of equilibrium statistical mechanics in isolated quantum systems, more specifically, the phenomena of equilibration and thermalization. How these two very common and intuitive phenomena arise from unitary evolution is a riddle that, despite intense research, is not as of yet fully solved. We will argue that while it is hard to derive this phenomenology from the microscopic description of a specific physical system, such phenomena are \emph{typical}, in the sense that they occur in the vast majority of physical systems, and under some assumptions their absence is sensitive to small, hard to detect changes in the underlying Hamiltonian.

We will then move on to systems which seem to avoid thermalization by retaining memory of their initial conditions due to a phenomenon known as many-body localization. Most systems known to exhibit such a behavior are so called disordered systems, described by an ensemble of Hamiltonians in which certain couplings are drawn randomly. We will discuss the notion of local integrals of motion in many-body localized systems and describe a method to measure their properties by observing the spread of entanglement in the system. Following this, we will more closely examine the role of randomness and disorder in the emergence of many-body localization by examining the local integral of motions of disorder-free systems which appear to resist thermalization.

Finally, we will discuss how randomizing a quantum system can allow one to extract information about its state. More specifically, we describe an algorithm which interpolates between two known extreme schemes, one allowing to capture only local properties, and the other only globally, and show that this intermediate version is able to perform efficiently in both regimes.

To successfully interact with the environment, humans must robustly encode sensory inputs into neural representations and translate these representations into adaptive behavior. In this thesis, I conducted three empirical studies targeting particular neural mechanisms entailed in this transition from sensory inputs to perceptual decisions. In Study 1, I probed the robustness of core visual processing mechanisms by characterizing and comparing the neural dynamics of object recognition for natural photographs and abstracted line drawings. This revealed that core visual processing mechanisms in the brain are robust to the abstraction of substantial amounts of visual information, such as in line drawings. In Study 2, I investigated the influence of feedback processing on object representations by comparing the neural dynamics of object recognition for stimuli that were either rapidly followed by a masking stimulus or followed only after a substantial delay. This revealed that feedback processing fundamentally shapes visual representations in the brain, first in early than in high-level visual cortex. Feedback enhances the persistence of visual representations, causes a shift in the representational format in high-level visual cortex, and affects distinct spectro-temporal windows in the theta to beta frequency bands. Finally, in Study 3, I examined the link between neural representations of real-world scenes and behavior under varying task demands. The findings showed that distinct visual representations in the brain are behaviorally relevant depending on the task, that mid-level visual features underlie these behaviorally relevant representations, and that visual representations can interfere with behavior given task demands that do not align with the represented information. By demonstrating the robustness of core visual processing mechanisms to visual abstractions and by characterizing how feedback processing dynamically shapes visual processing, the findings in Study 1 and 2 provide complimentary insights into the neural mechanisms that enable robust encoding of visual information. By identifying and characterizing visual representations relevant for behavior across different task demands, Study 3 provides novel insights into the translation of sensory information into perceptual decisions. Collectively, these results contribute to a large body of research on visual recognition and perceptual decision making, provide potential new theoretical frameworks for understanding the underlying mechanisms, and guide the way for future research that directly tests and refines these theories.

Labor markets and individual decisions are highly interrelated. This dissertation analyzes important intersections between the two. Its four chapters are based on large, mostly admin- istrative micro data. The last three chapters apply innovative quasi-experimental methods, while the first chapter provides a descriptive analysis.

The first chapter describes recent immigration patterns in Germany, particularly from the EU. It introduces an innovative imputation method to identify recent labor market immigrants. This allows us to the inspect in detail who are the immigrants, who stay in Germany and who are those that leave Germany again. We show that the labor market success in Germany plays an important role.

The second chapter inspects the effects of this recent EU immigration on the German labor market. EU Eastern Enlargement elicited a rise in (temporary) labor market oriented immi- gration to Germany starting in May 2011. Taking into account that not all immigrants stay permanently and that outmigration flows are selective, this paper classifies recent EU im- migrants into “new arrivals” and “stayers” drawing on administrative social security data (2007-2019). This novel strategy allows us to separately identify their potentially opposing short- and medium-run effects on labor market outcomes in Germany. We find a transitory negative wage effect among German nationals at the bottom of the wage distribution; and a permanent positive effect on (full-time) employment.

In the third chapter, I investigate employment differences within couples and use German administrative data as well as survey data. Gender gaps in employment have narrowed but remain substantial, particularly among couples. To estimate how improved female wage op- portunities influence partners’ employment choices, I exploit demand-driven wage changes in job tasks and German administrative data. Results indicate women respond positively, al- beit at a diminishing rate, to relative wage improvements, while male partners also increase their labor supply in response. Consequently, the work hours gap within couples narrows, but doesn’t close and even widens in certain groups. Potential explanations for these patterns building on Becker’s household model include comparative advantages for women, and rel- ative income preferences and gender identity norms for men.

The last chapter, looks at a family policy in Denmark and uses administrative data of the full population. It examines Denmarks 1984 parental leave reform, among the first to grant fathers paid leave. Using a regression discontinuity design, we find that introducing shared parental leave mainly increased mothers leave, with modest paternal uptake. Adding two weeks of earmarked leave for fathers significantly raised their participation without reducing mothers leave. Fathers who took leave once were more likely to do so again. However, we find no evidence of intergenerational effects on the affected childrens fertility or parental leave behavior.

Photosystems I and II (PSI, PSII) are two large protein complexes that are part of the electron transport chain of oxygenic photosynthesis in plants, algae, and cyanobacteria. The activity of these photosystems is indispensable in oxygenic photosynthesis, the process that powers life on Earth by converting solar energy into chemical energy. PSII harbors the light-driven water splitting process, which results in the removal of four protons and four electrons from two water molecules. This process is coupled to the release of molecular oxygen (O2) and is thus also referred to as photosynthetic oxygen evolution or oxygen evolution reaction (OER); it is responsible for creating the oxygen in the Earth’s atmosphere. The OER cycle of PSII (S-state cycle) involves four successive photon absorption events, which lead to the stepwise accumulation of four oxidation equivalents at the catalytic site, a protein-bound Mn4CaOx cluster, prior to O2 formation. In contrast, the PSI reactions can be discussed as a one-photon process: upon absorption, charge separation takes place and the electron is transported down one of two paths (the A- or B-branch), finally reducing the mobile electron carrier ferredoxin. In both photosystems, the light-induced processes are still insufficiently understood regarding the temporal sequence of atomistic events.

The focus of this thesis is the investigation of the S-state transitions in PSII by means of time-resolved single-frequency infrared (TRSF-IR) spectroscopy in the wavenumber range from 1800 cm–1 to 1300 cm–1. Measurements on spinach PSII membrane particles in H2O, D2O and at several different pH values allowed for the characterization of the kinetics of three S-state transitions (S1→S2, S2→S3 and S3→S0). Global analysis of time-resolved spectral data sets resulted in decay-associated spectra (DAS), which are essentially spectral fingerprints of individual kinetic phases. The DAS of the proton transfer (PT) and electron transfer (ET) phases of the O2-producing S3→S0 transition mostly reproduced the results of a previous step-scan Fourier-transform infrared (FTIR) study (Greife et al., 2023), but also managed to resolve a crucial deuteration-induced band shift, which was left undetected by the FTIR study.

Global analysis of a data set on a spinach PSII sample depleted of its Mn4CaOx cluster resulted in DAS that showed great similarity to previously reported FTIR spectra of two PSII co-factors (QA and P680). Double difference spectra of intact minus Mn depleted PSII revealed that certain spectral regions are likely to be more strongly affected by a high fraction of broken PSII centers than others.

The comparative analysis of spinach PSII membranes to PSII core particles from Thermosynechococcus vestitus BP-1 (T. vestitus) and Synechocystis sp. PCC 6803 revealed that while at some wavenumbers the IR difference transients are very similar to each other, they differ drastically at others. It was found that the likely source of this observation is a differing amount of broken PSII centers in the different samples. Measurements of T. vestitus in D2O revealed similar kinetic isotope effects as observed for spinach PSII. PSII from Synechocystis carrying either the D1-N298A or the D1-D61A mutation was investigated and compared to wild-type PSII. While the monophasic O2-producing ET step of the S3→S0 transition was found to be drastically slowed in D1-D61A, it was found to be biphasic in D1-N298A. We assign the two observed kinetic phases to (i) O2-evolution occurring at a similar rate as in wildtype PSII and (ii) strongly decelerated substrate water insertion into the Mn4CaOx cluster, which in wild-type PSII occurs faster than the rate-limiting step and is therefore usually not spectroscopically detectable.

Measurements on three PSI wild-type variants allowed for the first ever IR spectroscopic observation of ET down the A- and B-branch at room temperature. Global analysis of the nanosecond kinetics resulted in DAS of forward ET down the A-branch. All in all, TRSF-IR measurements allowed for the kinetic and spectral characterization of various PSII and PSI samples, resulting in a small contribution toward a full understanding of the molecular mechanisms of oxygenic photosynthesis.

Hintergrund: Nach einem Schlaganfall zählt Depression zu der häufigsten neuropsychiatrischen Komplikation. In der Gesamtbevölkerung ist C-reaktives Protein als Prädiktor für eine Depression etabliert. Hier wollen wir untersuchen, ob hochsensitives C-reaktives Protein (hs-CRP) bei Patient:innen nach einem milden bis moderatem Schlaganfall über die Zeit mit depressiven Symptomen assoziiert ist und ob es einen Unterschied bezüglich der Ausprägung bei Männern und Frauen gibt. Methoden: Wir rekrutierten Patient:innen mit einem erstmaligen Schlaganfall für die Prospective Cohort with Incident Stroke Berlin (NCT01363856). Die depressive Symptomlast der Patient:innen wurde mit dem validierten CES-D (Center for Epidemiologic Studies Depression Scale) Fragebogen an insgesamt drei Beobachtungszeitpunkten über drei Jahre erfasst, wobei ein CES-D über dem Schwellenwert von 16 Punkten auf eine klinisch signifikante Depression hindeutet. Einflussfaktoren wurden systematisch mit directed acyclic graphs (DAG) identifiziert und für die adjustierten Berechnungen genutzt. Den Zusammenhang von hs-CRP zu CES-D Werten an den einzelnen Jahren berechneten wir mit einem linearen Modell. Mit gemischten linearen Modellen berechneten wir die Effektstärke von hs-CRP auf CES-D Werten über drei Jahre und in den Subgruppenanalysen berechneten wir zusätzlich, ob 1) eine Dosis-Wirkungsbeziehung von hs-CRP zu den CES-D Werten über die Zeit vorliegt 2) sich die Effektstärke von subklinischen hs-CRP (< 10 mg/l) zu CES-D Werten über die Zeit unterscheidet 3) ergänzende Störfaktoren das Modell verbessern. In allen Analysen inkludierten wir einen Interaktionsterm, um einen Unterschied zwischen den Geschlechtern zu identifizieren. Ergebnisse: Wir analysierten 585 Patient:innen mit einem mildem bis moderatem ischämischem Schlaganfall. Die Patient:innen waren durchschnittlich 67 (SD 13) Jahre alt, 39 % waren weiblich und der mediane NIHSS Score betrug 3 (IQR 1 -4). Im ersten Jahr gaben 20% der Teilnehmenden einen CES-D Wert von ≥ 16 an. Im zweiten Jahr waren es 21% und im dritten Jahr 17%. In unserem linear gemischten Modell waren höhere log-transformierten hs-CRP Level mit höheren CES-D Werten assoziiert (β=1,28; (95% CI, 0,22–2,34)). Für Frauen bestätigt sich diese Assoziation in der Interaktionsanalyse (β=2,33; (95% CI, 0,71–3,95)) und allen Subgruppenanalysen. Schlussfolgerung: In unserer Kohorte von Patient:innen mit mildem bis moderatem erstmaligem ischämischen Schlaganfall zeigen sich erhöhte hochsensitive C-reaktives Protein Level bei Studieneinschluss mit höheren depressiven Symptomen über drei Jahre assoziiert und werden durch die Subgruppenanalysen bestätigt. In den Interaktionsanalyse konnten wir zeigen, dass sich diese Assoziation insbesondere für Frauen nachweisen lässt.

Mechanosensors convert physical stimuli into chemical signals, influencing numerous biological processes and disease mechanisms. This thesis establishes a benchmark system for controlling mechanosensitive ion channels using light. The mechanosensitive channel of large conductance (MscL), activated by membrane tension, was reconstituted in membranes containing the photoswitchable lipid AzoPC. AzoPC, an azobenzene-modified phospholipid, generates membrane tension when exposed to blue or UV light. The photolipid’s light-induced tension was studied using Langmuir-Blodgett troughs, polarized FTIR spectroscopy, and DFT simulations. MscL reconstituted in various systems, including liposomes and nanodiscs with AzoPC, exhibited reversible backbone movement under light-induced tension, gating the channel to an intermediate state. This work lays the groundwork for light-controlled mechanosensitive ion channels, advancing fundamental biology and therapeutic tool development.

Ziel der vorliegenden Studie war es, die Effekte pflanzlicher Proteinquellen in Futtermischungen mit und ohne Getreideanteile auf die scheinbare Verdaulichkeit der Nährstoffe, die fäkalen mikrobiellen Metabolite, die Mikrobiota sowie Harn- und Blutparameter bei Hunden zu untersuchen. In dieser Studie wurden 10 Beagles mit Diäten gefüttert, die entweder Geflügel- oder Leguminosenprotein (Erbsen- und Bohnenkonzentrat) sowie alternativ Weizen oder Quinoa enthielten. Das Studiendesign folgte einem Cross-Over-Design mit einem drei-faktoriellen Aufbau (Kohlenhydratquelle, Proteinquelle und -konzentration). Die Proteinkonzentrationen waren bedarfsdeckend oder auf das 1,5-fache erhöht. Nach einer dreiwöchigen Anpassungsphase wurden Kot-, Urin- und Blutproben entnommen und analysiert, um die Verdaulichkeit der Nährstoffe sowie die Konzentration von Mengen- und Spurenelementen zu bestimmen. Zusätzlich wurden in den Kotproben bakterielle Metabolite und die Zusammensetzung der intestinalen Mikrobiota analysiert. Das Blut wurde auf hämatologische und klinische Parameter sowie Aminosäurekonzentrationen untersucht. Der Urin wurde auf Anionen, Kationen und die Zusammensetzung analysiert. Die Ergebnisse zeigten, dass pflanzliche Proteine eine höhere scheinbare Verdaulichkeit aufwiesen als tierische Proteine. Die Diäten mit Weizen und Geflügelmehl hatten die niedrigste scheinbare Proteinverdaulichkeit, während die Diätvarianten Quinoa in Kombination mit Erbsen und Bohnen und sowie Weizen mit dem 1,5-fachen Gehalt an pflanzlichen Proteinquellen die höchste scheinbare Verdaulichkeit aufwiesen. Für die Verdaulichkeit von Kalium, Magnesium und Natrium hatte der unterschiedliche Mineralstoffgehalt in den acht Diäten einen Einfluss. Die Verdaulichkeit der Mengenelemente Calcium, Phosphor, Magnesium und Natrium sowie der Spurenelemente Kupfer und Zink war nicht eindeutig durch die Diäten beeinflusst. Diäten mit tierischen Proteinen sowie die proteinreichen Rationsvarianten erhöhten die Ammoniumkonzentration in den Fäzes. Weizenhaltige Diäten erhöhten die fäkalen D- und L-Laktat-Konzentrationen, mit Ausnahme der weizenhaltigen Diäten in Kombination mit Geflügelmehl. Diäten mit Quinoa führten zu erhöhten Konzentrationen von Phenol und Indol im Kot. Der Einsatz tierischer Proteine und eine erhöhte Proteinkonzentration führten zu höheren fäkalen Konzentrationen von i-Buttersäure und i-Valeriansäure. Diätvariationen mit Quinoa erhöhten hingegen die Konzentrationen von Essigsäure, Propionsäure, i-Buttersäure, i-Valeriansäure sowie den Gesamtgehalt an kurzkettigen Fettsäuren. Die Proteinquellen beeinflussten die bakterielle Diversität im Hundekot, wobei tierische Proteine die höchste Diversität der fäkalen Mikrobiota und einen Anstieg der Fusobakterien verursachten. Pflanzliche Proteine begünstigten hingegen das relative Vorkommen von Actinobacterium spp. Diäten auf Basis von Geflügelmehl führten zu einem Anstieg des Vorkommens von Fusobacterium, Peptoclostridium und Sellimonas spp., während Diäten, die pflanzliche Proteine enthielten, ein erhöhtes relatives Vorkommen von Bifidobacterium, Lactobacillus und Prevotella spp. bewirkten. Ein Anstieg des relativen Vorkommens der Genera Peptoclostridium und Streptococcus wurde durch eine erhöhte Proteinzufuhr beobachtet. Die pH-Werte im Urin waren bei Hunden, die mit Weizen und Geflügelprotein gefüttert wurden, niedriger (5,73 bis 6,30) als bei Hunden, die mit Quinoa gefüttert wurden (7,20 bis 7,47). Die Konzentrationen von Phosphat, Citrat und Struvit im Urin waren von dem Proteingehalt und der Proteinquelle der Diäten abhängig. Ein höherer Proteingehalt führte zu geringeren Phosphatkonzentrationen, während Citrat und die RSS-Werte für Struvit trotz signifikanter Effekte variabel blieben. Die in den Diäten enthaltenen Erbsen und Bohnen bewirkten eine relative Übersättigung mit Struvit. Die Proteinquellen führten nur zu geringfügigen Veränderungen der hämatologischen Parameter, während die Serumharnstoff- und Albuminkonzentrationen signifikant durch den Proteingehalt in den Diäten beeinflusst wurden. Bei der Verwendung von Quinoa in den Diäten stieg die Aktivität der Alanin-Aminotransferase im Serum der Hunde im Vergleich zur Fütterung einer weizenhaltigen Diät signifikant an. Zudem wurden höhere Bilirubinkonzentrationen im Serum beobachtet. Die Aktivität der alkalischen Phosphatase im Serum erhöhte sich bei der Fütterung von Quinoa im Vergleich zu den weizenhaltigen Diätvariationen (p=0,030). Die Aktivität der alkalischen Phosphatase war niedriger, wenn proteinreichere Diäten verfüttert wurden. Zusammenfassend zeigen die Ergebnisse dieser Studie, dass sowohl pflanzliche Protein-quellen als auch Quinoa als sogenanntes Pseudogetreide in der Hundeernährung verwendet werden können. Nach den vorliegenden Untersuchungen hat sich ein moderater Proteingehalt als günstig für Hunde erwiesen, da dies zu weniger Proteinabbauprodukten führt, die potenziell nachteilige Auswirkungen auf den Organismus haben können.

The dissertation argues for a new understanding of the concept of sufficiency in arguments for justice and applies this new understanding to the educational justice debate. The first three chapters of the dissertation explain the way that sufficiency has been understood in recent debates about justice and argue against this usage and for a new understanding of sufficiency. The last two chapters argue that this new understanding of sufficiency improves our understanding of educational adequacy for democratic citizenship in debates about educational justice.

The effects of climate change are becoming more frequent and extreme; effects such as droughts, floods, heat and cold waves are putting the lives of millions of people at risk. The main contributor to climate change is the use of fossil fuels such as coal, oil and gas;1 hence, there is a need to replace that source of energy with renewable energy. Solar energy is the third most used renewable energy, after hydropower and wind energy. The material that is mostly used for solar cells is silicon due to its high efficiency and stability; however, its production is expensive and highly energy-consuming. In the last years, other materials2,3 have risen to offer a more sustainable approach, but despite their many advantages, they cannot compete in terms of efficiency. Hybrid halide perovskites (HHPs) have drawn the attention of the scientific community, not only for their steep increase in power conversion efficiency during the last decade, up to 26.7%4 in 2024 but also for using low-cost solution-based processing methods. Despite their popularity, it is not yet fully understood what the formation mechanism of HHPs is. This work aims to bring more clarity on how HHPs form from solution, focusing on how the solvent used interacts with the precursors before the perovskite is formed. For this reason, the precursor solution of MAPbI3 (MA= CH3NH3) was studied with 4 common solvents used to produce perovskite layers: γ-butyrolactone (GBL), N,N-dimethylformamide (DMF), N-Methyl-2-pyrrolidone (NMP), dimethyl sulfoxide (DMSO) and mixtures thereof. Furthermore, since HHPs present changes in the bandgap when the composition is modified,5 the effect of substituting I- for Br- and Cl- and substituting MA+ for FA+ (HC(NH2)2) and alkali metals (Na+, K+, Rb+, Cs+) was studied as well. Small angle X-ray scattering was the method of choice to investigate the precursor solutions since it can determine the size, shape, interaction, and average distance between the scattering objects in solutions in the range of 0.5 – 100 nm. The results obtained from SAXS can be explained by a core-shell model, where the core is a [PbI6], which can be arranged as a single octahedron or as a corner-sharing octahedra and the shell is formed by randomly oriented solvent molecules. When the A-cation is molecular (FA+, MA+), it has no influence on the arrangement of the scattering objects, but when the A-cation is inorganic, the [PbI6] octahedra of adjacent scattering objects are surrounded by a solvent shell with molecules or by an A-cation shell. The results from SAXS showed higher polydispersity in the samples with an inorganic A-cation, which is in agreement with the proposed model. Changing the I- for Br- favours the single octahedron arrangement in the core, whereas when Cl- is used as a halide, there is no evidence of agglomeration in the precursor solution.

Ziel der kumulativen Habilitationsschrift war es, ethische Haltung und den Umgang mit Grenzentscheidungen aus verschiedenen Perspektiven zu erfassen. Hierzu wurden Umfrage-basierte Studien unter verschiedenen perinatologischen Berufsgruppen zum einen und der Bevölkerung und betroffenen Elternpaaren zum anderen durchgeführt.

Im Fokus der Befragungen standen jeweils die vielfältigen Aspekte und Einflüsse auf die elterliche Beratung und Entscheidungsfindung bei drohender extremer Frühgeburtlichkeit bzw. bei Feten mit pränataldiagnostisch gesicherten komplexen kardialen Fehlbildungen zu analysieren.

Zusammenfassend kann aus den erbrachten Studien abgeleitet werden, dass die Haltung und der Umgang mit medizin-ethischen Entscheidungen von individuellen Wertevorstellungen und professionsabhängigen Erfahrungen abhängig ist und sich in einem steten zeitlichen Wandel befindet. Um eine gemeinsame Sprache zwischen Ärzt*innen und Patient*innen bzw. Stellvertreter*innen in Beratungsgesprächen zu finden, kann es wichtig sein, Informations- und Wissenslücken in der Bevölkerung zu schließen.

Diatoms are an outstanding group of unicellular microalgae that can be found in almost all aquatic ecosystems, playing critical roles in the global carbon fixation and oxygen cycle. The cell wall surrounding diatom living cells, named frustule, is synthesized from amorphous hydrated silica with outstanding properties and plenty of geometries and ultrastructures varying between different species. The frustule consists of subcomponents; valves and girdle bands, held together in the living state but can be extracted and retrieved after death. The retrieved valves/girdle bands exhibit an outstanding ultrastructure, including the presence of nano-/micro-pores arrays resembling the artificial photonic crystal slabs and diffraction gratings. That is why the optical properties and light modulation capabilities of these siliceous parts have recently captured a wide interest and have been suggested for several optical applications as an eco-friendly and cost-effective alternative to artificial structures. Despite the previous efforts to understand the light modulation capabilities of these frustules and their subcomponents, more efforts are still required, and many missing gaps need to be filled. Therefore, this thesis aims to deepen the understanding of their light modulation capabilities, while focusing on their optical near field and Fresnel regime. That could help increase the applicability of their valves in optical applications and understanding the possible photobiological roles of their frustules. Additionally, the thesis also aims to investigate implementing the extracted clean valves as optical building blocks in photonic and optoelectronic applications, which adds to the previous efforts in the literature.

First, a novel analytical approach has been employed to numerically analysis the light modulation capabilities of the valve/frustule of small-size pennate diatom Gomphonema parvulum. The simulations were based on the 2D finite element frequency domain (FEFD) method. This approach enabled revealing the correlation of distinct optical phenomena; including thin-film interference, waveguiding, diffraction-driven focusing, photonic jet generation, Talbot effect, and guided-mode resonance, to the distinct optical elements comprising the valve/frustule. Such phenomena influence the valves’/frustules’ optical near-field and Fresnel regime and overlap in a wavelength-dependent manner to yield a complex interference pattern. Moreover, in order to broaden the understanding of the diffraction-driven focusing by diatom valves, the far-field optical microscopy techniques have been employed to study this behavior mainly in the Fresnel regime of structurally distinct valves covering a wide range of geometries, ultrastructure, and sizes, showing that this phenomenon could be more widespread among diatoms. The latter study showed, for the first time, that the diatom valves could also focus the light when being illuminated from the side. The 2D FEFD numerical analysis showed an ability to predict and analytically explain such behavior. Furthermore, the optical near-field of the valves of pennate diatom Gomphonema parvulum and centric diatom Aulacosira sp. have been studied utilizing an aperture-type scanning optical near-field microscopy (a-SNOM), operated in illumination and collection mode. The latter being used for the first time to study the optical near-field of diatom valves. The SNOM results, which provided new insights especially that of collection mode, have also been compared to the 2D FEFD numerical analysis results. Additionally, a novel methodology has been developed to study the 2D periodicities and symmetries of diatoms’ pore arrays based on image processing and analysis techniques, especially the 2D autocorrelation function analysis, offering an accurate and reproducible methodology that could help assess these pore arrays for relevant applications. Toward applications, a novel method for fabricating diatom-based SERS hybrid substrates was employed by obtaining a smooth ultrathin gold film over diatom valves. This method allowed comparing the ability of structurally distinct valves in enhancing SERS signal, where the magnitude of the enhancement likely depended on the valve ultrastructure. Additionally, a preliminary study on incorporating diatom valves into organic MISM photodetectors was also carried out.

In conclusion, I believe that this thesis offers new insights and deeper analytical understanding of the abilities of diatom valves/frustules to modulate light. On the one hand, this answers some questions while opening up many new.

Neben spenderabhängigen Einflussfaktoren und einem unvermeidbaren Endothelzellverlust im Rahmen einer passiven Organkultivierung, auch wenn diese aktuell den Goldstandard darstellt, hat die Augenhornhautbank Einfluss auf die Endothelzelldichte von Augenhornhäuten. Die fehleranfällige Bestimmung der cornealen Endothelzelldichte von Spenderaugenhornhäuten lässt sich durch eine computerbasierte Analyse zweifelsfrei positiv beeinflussen. Wir konnten zeigen, dass die entwickelte Bildanalysesoftware vollautomatisch valide und reproduzierbar die zentrale Endothelzelldichte bestimmt. Unsere Untersuchungen fanden einen relevanten Endothelzellverlust durch die Verwendung einer stärker hypoosmolaren Substanz für die lichtmikroskopische Visualisierung dieser Zellen. Durch die Verwendung einer möglichst gering hypoosmolaren Substanz mit einer niedrigen Expositonsdauer kann die Endothelzellschicht im Rahmen der Organkultivierung von Spenderaugenhornhäuten geschützt werden. Hypotherme und hypertherme Temperaturänderungen zeigten in unseren Arbeiten in einem Bereich zwischen +4 und +42°C keinen Effekt auf die cornealen Endothelzellen von organkultivierten Augenhornhäuten. Temperaturen unterhalb des Gefrierpunktes und über +42°C müssen, z.B. während des Transportes von Augenhornhauttransplantaten zum Empfänger, streng vermieden werden, da ansonsten eine komplette Nekrose der empfindlichen Endothelzellschicht eintritt. Die aktuellen Forschungen zu einer aktiven Organkultivierungsform von Spenderaugenhornhäuten ergaben vielversprechende Ergebnisse hinsichtlich einer Protektion der Endothelzellen. Dabei muss auf die bekannten positiven Effekte der etablierten Organkultur nicht verzichtet werden. Solle sich dieser Ansatz erfolgreich in die Routine etablieren lassen, wird es voraussichtlich zu einer echten Evolution der Konservierung von Spenderaugenhornhäuten kommen.

There are a number of threats to the biodiversity of Southeast Asia. This global biodiversity hotspot has experienced surges in commercial poaching, particularly in mainland Southeast Asia, extirpating large mammals like tigers and rhinoceros from prime habitat in some locations. In maritime Southeast Asia, large-scale habitat degradation and loss has been driven by selective logging and industrial commodity plantations. With many ongoing initiatives to improve land-use management and protect biodiversity led by regional governments, it is useful to measure the impacts of these initiatives on biodiversity in a quantifiable way. The first aim of this dissertation was to examine the impacts of forest management at multiple scales on one particular species of high conservation value, while the second aim was to test how spatial modelling can improve protection for biodiversity. The location for this study was Sabah, a Malaysian state on the island of Borneo. The overall distribution of sun bears Helarctos malayanus across the forested landscapes of Sabah was previously not quantified. We used the large amount of sun bear data available from the many camera trap studies across the state and applied occupancy models to assess and predict the current and future suitability of habitats for the species (chapter 2). We found that all large forested areas of Sabah were predicted to be suitable, with almost half of the area predicted to be suitable within forests where logging and plantation development is occurring or will occur in the future. Forests of higher aboveground carbon density (i.e. more intact forests) were predicted to be more suitable than forests of lower aboveground carbon density. We conclude that future conversions of forests into plantations will have an impact on sun bears. In addition, enough resources should continue to be channeled towards anti-poaching activities to protect the large forested landscapes where bears currently live. Sabah’s sustainable forest management, in particular reduced impact logging, has been practiced for almost 20 years. In two particular sites certified by the Forest Stewardship Council, Deramakot and FMU 17A, we used sun bear data from two successive survey periods four years apart with occupancy models to investigate how sun bear habitat suitability has changed (chapter 3). Our findings revealed that overall sun bear habitat suitability increased, but not significantly, over a 4 year period throughout Deramakot and FMU 17A. There were noticeable reductions only in areas undergoing active logging (Deramakot) and one area of tree plantation (FMU 17A). This shows that sustainable forest management can provide suitable habitat for sun bears over time, as long as protection from poaching is in place. Understanding how different poaching offenders use the landscape can help managers of protected and conserved areas plan anti-poaching operations. We used a three year anti-poaching patrol dataset in an occupancy framework to identify areas of high “use” by two distinct offender types, gaharu collectors and wildlife hunters, in Deramakot and FMU 17A (chapter 4). We found that our model predictions of offender “hotspots” overlapped with areas of known poaching activity. We highlight the importance of site-level ranger knowledge in anti-poaching planning and the usefulness of applying occupancy-based predictions in policing vast forested landscapes.

Background: The Eurotransplant Senior Program (ESP) was established in 1999. It provides kidney transplants (≥ 65 years) to recipients with an age of ≥ 65 years. In 2019, the ESP celebrated its 20th anniversary. For this period, we compared the survival times of patients transplanted in the ESP with those of dialysis patients on the ESP waiting list.

Methods: All patients ≥ 65 years of age who were actively on the waiting list of the ESP at least once from 01.01.1999 to 31.12.2019 at Charité Campus Mitte and Charité Campus Virchow Klinikum and were listed for their first post-mortem kidney donation were included. Survival time analyses were performed using the Kaplan-Meier method. The starting point was the first active listing in the ESP or the 65th birthday if transferring from the ETKAS allocation to the ESP. Survival analyses were conducted as landmark analyses with landmarks (LM) at 6, 12, 18 and 24 months. At the time of the LM, cohorts were divided into kidney transplantation (NTX) and waiting list (WTL). Sensitivity analyses were performed to analyze only patients whose first listing was after the age of 65. In addition, this separate population was stratified by median age and re-examined.

Results: The total cohort included 783 patients (58.6% NTX, 61.2% male), of which 7 patients were lost to follow-up. The LM 6, 12, 18, 24 cohorts included 732, 683, 641, 585 patients, respectively. None of the landmark analyses showed a survival advantage for the NTX or WTL group. The 5-year survival in the age-independent analyses was 73.1% (NTX) vs. 72% (WTL) in LM6, 74.4% (NTX) vs. 75.2% (WTL) in LM12, 77.5% (NTX) vs. 77.4% (WTL) in LM18, 80.7% (NTX) vs. 80.0% (WTL) in LM24.

Conclusion: This study is one of the first to describe that there is no significant difference in survival time between dialyzed and kidney transplanted patients in the ESP. It is also one of the first to use landmark analysis to evaluate survival times in the ESP. Our results show that kidney transplantation in older patients needs to be carefully discussed. Factors such as comorbidities, medication, changes in quality of life or duration of dialysis were not taken into account in this study, but should be included in further studies.

The objective of the following paper is to determine the arterial inflow resistance of brachial arteries at typical arteriovenous anastomosis locations based on brachial angiographies. The clinically significant background to this is the influence of inflow resistance on peripheral perfusion pressure and thus on peripheral tissue perfusion in cases where AV connections have been established. The arterial inflow resistance was calculated on the basis of the Hagen-Poisseuille equation by performing angiographies to measure the diameter and length of the vascular segments from the origin of the A. subclavia to the level of the AV anastomosis under investigation. The flow resistance was calculated by adding the inflow resistance measured for each of the upstream vascular segments. Since the angiography images were not calibrated, the diameter of the A. subclavia constitutes the initial value for the calibration and measurement process. The results of the study showed an almost exponential increase in the inflow resistance moving from the centre to the periphery of the vascular tree of the brachial arteries. In the patients examined, the inflow resistance in the distal arterial segments of the lower arm was up to 200 times greater than that in the A. axillaris. No pattern encompassing concomitant diseases, age, gender and body side could be identified. The informative value of the study is limited due to the small patient cohort. Awareness of the influence of inflow resistance on peripheral tissue perfusion could enable inadequate peripheral perfusion to be corrected by feeding the AV vessel from a more centrally located anastomosis (proximalisation of the AV anastomosis).

The synchronization of cellular activity during neuronal oscillations is considered an established mechanism of central nervous system processes. In particular, oscillations in the gamma-frequency range (30 – 80 Hertz) are regarded as biomarkers for cognitive abilities, as their spectral amplitude correlates with cortical performance in health and disease. However, it remains elusive to what extent synaptic plasticity, as occurs following learning, can influence the spectral amplitude of gamma-oscillations, and whether there is an identifiable cellular basis for the plasticity of gamma-oscillations. This work presents a robust protocol for quantifying and mechanistically dissecting the long-term, activity-dependent increase in amplitude of ex vivo gamma-oscillations ("gamma-potentiation") using electrophysiological recordings. In acute brain slices from the mouse hippocampus, it is demonstrated that the one-time induction of gamma-oscillations leads to a long-lasting increase in the spectral amplitude of subsequent gamma-oscillations. Using pharmacological and genetic interventions it is demonstrated that gamma-potentiation can be fully explained by activity-dependent plasticity of glutamatergic synapses onto parvalbumin-positive interneurons (PVI). Two cell-type-specific metabotropic pathways specific to PVIs are required for gamma-potentiation: A canonical Gq-pathway activated by group I metabotropic glutamate receptors that re-cruits protein kinase C, and a Gi-sensitive pathway that recruits protein kinase A. Ulti-mately, gamma-potentiation is mediated by a conductance increase of calcium-permeable AMPA receptors on PVIs. This work identifies a mutual relationship between synaptic plasticity of PVIs and network plasticity of gamma-oscillations: Gamma-oscillations induce plasticity in PVIs, which translates to an increased spectral amplitude of subsequent gamma-oscillations. This principle of cell-to-network plasticity holds potential for an improved understand-ing of memory processes in health, adds to current models of neuropsychiatric patho-physiology and, finally, may guide future therapeutic strategies.

Das orale Plattenepithelkarzinom (oral squamous cell carcinoma; OSCC) gehört zu den häufigsten malignen Tumorerkrankungen in der Kopf-Hals-Region, wobei eine stetig steigende Inzidenz zu beobachten ist (1). Die Erkrankung weist trotz intensiver Forschung seit Dekaden eine weitgehend unveränderte 5-Jahres-Überlebensrate von ca. 50-60 % auf (2). Entscheidend für die klinischen Leitlinien bezüglich der Behandlung eines oralen Plattenepithelkarzinoms ist primär die TNM-Klassifizierung (3). Das TNM-Stadium wird in seiner Funktion als maßgeblicher Parameter heutzutage jedoch zunehmend hinterfragt, da es versäumt, Fälle von Patient:innen abzugrenzen, welche auch in einem vermeintlich frühen Stadium der Erkrankung einen aggressiveren Verlauf zeigen (3). Vielmehr wird es als entscheidend erachtet, dass bei Patient:innen mit oralem Plattenepithelkarzinom neben dem TNM-Stadium auch prognostische Biomarker Berücksichtigung finden, um gezielt multimodale Therapieansätze wählen zu können. Ziel der vorliegenden Arbeit war es, auf der Basis demografischer Daten sowie histopathologischer Präparate von insgesamt 558 Patient:innen mit oralem Plattenepithelkarzinom erstmals den Einfluss des Rezeptors RHAMM (Rezeptor für Hyaluronsäure-vermittelte Motilität) und tumorinfiltrierender CD8+ T-Zellen auf das Outcome der Betroffenen zu untersuchen. Es konnte gezeigt werden, dass eine erhöhte RHAMM-Aktivität einen statistisch signifikanten Einfluss auf die Überlebensrate von Patient:innen hat, die sich in einem frühen Stadium der Erkrankung befinden. Gleichzeitig konnte kein signifikanter Einfluss tumorinfiltrierender CD8+ T-Zellen nachgewiesen werden, auch wenn dies in der aktuellen Literatur kontrovers diskutiert wird (4–6). Für eine finale Entscheidung dahingehend, ob und wie CD8+ T-Zellen und der Rezeptor RHAMM sich als Biomarker bei oralen OSCC eignen, reichen die in dieser Arbeit präsentierten Ergebnisse nicht aus. Dies erfordert zusätzliche Studien, welche auf die erarbeiteten Daten als Grundlage für weiterführende Untersuchungen zurückgreifen können.

Implant-associated infections are a medical challenge. One possibility for prevention and therapy is the use of antibiotic-coated implants. For this reason, the Fraunhofer Institute in Bremen developed a surface modification process that creates bottle-neck-shaped pores on implants coated with silver nanoparticles. The pores enable direct preoperative loading with antibiotically active solutions. The aim of this work was to characterize medullary nails modified in this way. Three groups were compared: an unmodified titanium nail as a control (K), a modified nail (porous with silver nanoparticles, (P)) and a modified nail additionally coated with 380-445 μg/cm² gentamicin (PG). Biocompatibility was to be investigated after implantation in rat femora. The aim was to determine whether loading with gentamicin affects osteointegration. Furthermore, the effectiveness for prevention of implant-associated osteomyelitis (OM) of the different groups should also be tested in an animal model. The biocompatibility of the modified intramedullary nails was confirmed. Greater osteointegration was observed for both porous variants compared with the smooth nail, with no significant difference between the two modified groups. In the push-out test, porous nails required an average of 1.84 N/mm², nails additionally loaded with gentamicin required 2.27 N/mm², and control nails required only 0.48 N/mm² to be pushed out of the bone (K to P p = 0.0153, K to PG p = 0.0007). In the histological examinations Bone-to-implant contact was 87% for porous intramedullary nails, 86% for those additionally coated with gentamicin, and 42% for control nails (p = 0.0032). To investigate the anti-infective properties of the modified nails, an S. aureus infection model was established for an OM. Infection was performed with a dose of 5 x 106 CFU and tested on both modified medullary nail variants. Nails coated with gentamicin showed no evidence of active OM and, like the uninfected control group, achieved an average OM score of 2. Porous nails without gentamicin achieved an average score of 4.5 with always positive bacterial detection. The infected negative control group (I) achieved an average score of 7.6 (I to G p = 0.0007) with bacterial detection in 6 of 7 animals. Both biocompatibility and infection prevention ability of the modified nails were demonstrated. However, intramedullary porous nails alone without additional gentamicin were not able to prevent infection altogether. Further studies are needed here to understand the underlying principles.

Einleitung: Spina bifida (SB) ist die häufigste Neuralrohrfehlbildung (NTD). Neuropathologische Befunde bei SB-Fällen werden oft mit ungenauer und sich überschneidender Terminologie angegeben. Die offenen Formen sind mit zerebralen Pathologien wie Hydrozephalus, Chiari II Malformation, Heterotopien und kortikalen Anomalien oder Gyrierungsstörungen verbunden. In dieser Studie haben wir die neuropathologischen Befunde des Rückenmarks und des Gehirns bei SB-Patienten systematisch analysiert. Methoden: Es wurde eine retrospektive Analyse und Reevaluation aller Fälle mit SB durchgeführt, die im Institut für Neuropathologie der Charité Berlin im Zeitraum von 1974 bis 2000 untersucht wurden. Insgesamt wurden 90 Fälle mit SB hinsichtlich ihres spezifischen Spina bifida aperta Subtyps reevaluiert, wobei 79 Fälle mit Spina bifida aperta (SBA) für die Analyse zerebraler Fehlbildungen eingeschlossen und mit 6 Spina bifida occulta (SBO) Fällen verglichen werden konnten. Es erfolgte eine detaillierte Analyse der Daten und fotografische Dokumentation der mikroskopischen Befunde sowie die Anfertigung zusätzlicher Schnitte und neuer Färbungen zur Klärung unklarer Diagnosen. Ergebnisse: Wir unterschieden die drei SBA-Phänotypen Meningozele, Myelomeningozele und Myeloschisis anhand der Lage des Rückenmarks und seiner Präsentation als geschlossenes Neuralrohr oder als offene embryonale Neuralplatte. Die Inzidenz der SB-Subtypen in den SBA-Fällen unserer autopsierten Föten betrug 35% für Myeloschisis (n=28), 32% für Myelomeningozele (n=26), 2% für Meningozele (n=2). 23 Fälle konnten retrospektiv nicht klassifiziert werden und wurden als SBA unspecified (AP) eingestuft. Das Ausmaß und die Lokalisation der Dysraphie variierten, wobei die lumbosakrale Manifestation eindeutig überwog. Während bei den SBO-Fällen keine Hirnfehlbildungen festgestellt wurden, wiesen 95% der SBA-Fälle Hirnfehlbildungen auf. Die wichtigsten festgestellten zerebralen Fehlbildungen waren Hydrozephalus (71%), Chiari II Fehlbildung (36%), Heterotopien (34%), andere Kleinhirnanomalien (36%), Gyrierungsstörungen (33%) und Ependymdefekte (29%). Ein Hydrozephalus wurde bereits in der 17. Schwangerschaftswoche beobachtet und war in hohem Maße mit Chiari II und ependymaler Denudation assoziiert. In 55% ging SBA mit weiteren Anomalien einher, die nicht primär das ZNS betrafen. Schlussfolgerung: Wir schlagen hiermit eine systematische Klassifikation der SB-Phänotypen vor, die die folgenden SBA-Subtypen umfasst: Myeloschisis (MYS); Myelomeningozele (MMC); Meningozele (ME). Außerdem konnten wir bei den meisten SBA-Fällen Hirnfehlbildungen nachweisen, bei SBO jedoch keine. Hydrozephalus und Chiari II Malformation können bei Föten mit Neuralrohrdefekten bereits in sehr frühen Schwangerschaftswochen nachgewiesen werden, was eher auf eine parallele Entwicklung der Fehlbildungen als auf eine strikte zeitliche Abfolge hindeutet.

Background: Age-related macular degeneration (AMD) stands as a primary cause of global vision impairment, presenting in advanced stages as either neovascular AMD (nAMD) or geographic atrophy. In clinical routine, nAMD is treated by anti-VEGF drugs. Short-chain fatty acids (SCFAs) are the primary bacterial metabolites produced by the fermentation of dietary fiber. The application of SCFAs demonstrated the potential in alleviating inflammation in retina and central nerve system (CNS), suggesting a sup-plementary role in nAMD treatment. This study aimed to assess the impact of SCFAs in a mouse model of laser-induced choroidal neovascularization (CNV) with properties of nAMD alongside exploring SCFA effects on microglial cells in vitro. Methods: An interventional study was conducted to evaluate SCFA effects in the mouse model of laser-induced CNV by means of fluorescein angiography, while volume of new blood vessels, microglia density, and GFAP expression in Müller cells were examined using immunofluorescence microscopy. RNA sequencing was em-ployed to characterize differential gene expression. Primary microglial cells, isolated from neonatal mouse cortex, were exposed to TNFα to simulate pathological condi-tions and effects of SCFA on microglia function were assessed by inflammatory cyto-kine secretion and phagocytic activity. The underlying pathways were elucidated through quantification O-GlcNAcylation and calcium imaging. Results: SCFAs have a protective effect in a mouse model of nAMD in both male and female. SCFAs mitigated laser lesion size, modulated vascular – related biological process, dampened inflammatory gene expression, and decreased microglial activation with a more pronounced effect in males. In females, SCFAs reduced volume of choroidal laser lesion and Müller cell gliosis. Additionally, SCFAs suppressed inflam-matory cytokine secretion and microglial phagocytosis in primary microglia derived from male, and inhibited O-GlcNAcylation in the corresponding female cohort. Conclusion: Overall, SCFA treatment demonstrated attenuation of vascularization and inflammation in a mouse model representative of nAMD.