• Publicationsclose
• Research softwareclose
• DE close
• Kölner UniversitätsPublikationsServer close

One of the main challenges for global public health in the modern world is the rising prevalence of obesity. Obtaining a better understanding of the dysregulated feeding behaviour that leads to obesity, by investigating the decision making and learning processes underlying it, could advance our capabilities in battling the obesity epidemic. Consequently, our aim in this study is to design an experiment that could evaluate these processes. We examined ten healthy participants using a modified version of the "probabilistic selection task". We used gustatory stimuli as a replacement for monetary rewards, to assess the effect of nutritional rewards on the learning behaviour. We subsequently analysed the behavioural results with computational modelling and combined this with imaging data simultaneously acquired with a functional magnetic resonance imaging (fMRI) multiband sequence. All participants in this study succeeded in interpreting and interacting with the gustatory stimuli appropriately. Performance on the task was affected by the subjective valuation of the reward. Participants whose motivation to drink the reward and liking of its taste decreased during the task presented difficulties correctly choosing the more rewarding cues. Computational modelling of the behaviour found that the so-called asymmetric learning model, in which positive and negative reinforcement are differently weighted, best explained the group. The acquired fMRI data was suboptimal and we did not detect the neurological activity we expected in the reward system, which is central to our scientific question. Thus, our study shows it is possible to implement the PST with gustatory stimuli. However, to evaluate the corresponding neurological activity, our fMRI configuration requires improvement. An optimised system could be used in further studies to improve our understanding of the neurobiological mechanisms of learning that lead to obesity and elucidate the role of food as a distinctive reinforcer.

While the number of publications on rotating active matter has rapidly increased in recent years, studies on purely hydrodynamically interacting rotors on the microscale are still rare, especially from the perspective of particle based hydrodynamic simulations. The work presented here targets to fill this gap. By means of high-performance computer simulations, performed in a highly parallelised fashion on graphics processing units, the dynamics of ensembles of up to 70,000 rotating colloids immersed in an explicit mesoscopic solvent consisting out of up to 30 million fluid particles, are investigated. Some of the results presented in this thesis have been worked out in collaboration with experimentalists, such that the theoretical considerations developed in this thesis are supported by experiments, and vice versa. The studied system, modelled in order to resemble the essential physics of the experimentally realisable system, consists out of rotating magnetic colloidal particles, i.e., (micro-)rotors, rotating in sync to an externally applied magnetic field, where the rotors solely interact via hydrodynamic and steric interactions. Overall, the agreement between simulations and experiments is very good, proving that hydrodynamic interactions play a key role in this and related systems. While already an isolated rotating colloid is driven out of equilibrium, only collections of two or more rotors have experimentally shown to be able to convert the rotational energy input into translational dynamics in an orbital rotating fashion. The rotating colloids inject circular flows into the fluid, such that detailed balance is broken, and it is not a priori known whether equilibrium properties of colloids can be extended to isolated rotating colloids. A joint theoretical and experimental analysis of isolated, pairs, and small groups of hydrodynamically interacting rotors is given in chapter 2. While the translational dynamics of isolated rotors effectively resemble the dynamics of non-rotating colloids, the orbital rotation of pairs of rotors can be described with leading order hydrodynamics and a two-dimensional analogy of Faxén’s law is derived. In chapter 3, a homogeneously distributed ensemble of rotors (bulk) as a realisation of a chiral active fluid is studied and it is explicitly shown computationally and experimentally that it carries odd viscosity. The mutual orbital translation of rotors and an increase of the effective solvent viscosity with rotor density lead to a non-monotonous behaviour of the average translational velocity. Meanwhile, the rotor suspension bears a finite osmotic compressibility resulting from the long-ranged nature of hydrody- namic interactions such that rotational and odd stresses are transmitted through the solvent also at small and intermediate rotor densities. Consequently, density inhomogeneities predicted for chiral active fluids with odd viscosity can be found and allow for an explicit measurement of odd viscosity in simulations and experiments. At intermediate densities, the collective dynamics shows the emergence of multi-scale vortices and chaotic motion which is identified as active turbulence with a self-similar power-law decay in the energy spectrum, showing that the injected energy on the rotor scale is transported to larger scales, similar to the inverse energy cascade of clas- sical two-dimensional turbulence. While either odd viscosity or active turbulence have been reported in chiral active matter previously, the system studied here shows that the emergence of both simultaneously is possible resulting from the osmotic compressibility and hydrodynamic mediation of odd and active stresses. The collective dynamics of colloids rotating out of phase, i.e., where a constant torque instead of a constant angular velocity is applied, is shown to be qualitatively very similar. However, at smaller densities, local density inhomogeneities imply position dependent angular velocities of the rotors resulting from inter-rotor friction. While the friction of a quasi-2D layer of active colloids with the substrate is often not easily modifiable in experiments, the incorporation of substrate friction into the simulation models typically implies a considerable increase in computational effort. In chapter 4, a very efficient way of incorporating the friction with a substrate into a two-dimensional multiparticle collision dynamics solvent is introduced, allowing for an explicit investigation of the influences of substrate on active dynamics. For the rotor fluid, it is explicitly shown that the influence of the substrate friction results in a cutoff of the hydrodynamic interaction length, such that the maximum size of the formed vortices is controlled by the substrate friction, also resulting in a cutoff in the energy spectrum, because energy is taken out of the system at the respective length. These findings are in agreement with the experiments. Since active particles in confinement are known to organise in states of collective dynamics, ensembles of rotationally actuated colloids are studied in circular confinement and in the presence of periodic obstacle lattices in chapters 5 and 6, respectively. The results show that the chaotic active turbulent transport of rotors in suspension can be enhanced and guided resulting from edge flows generated at the boundaries, as has recently been reported for a related chiral active system. The consequent collective rotor dynamics can be regarded as a superposition of active turbulent and imposed flows, leading to on average stationary flows. In contrast to the bulk dynamics, the imposed flows inject additional energy into the system on the long length scales, and the same scaling behaviour of the energy spectrum as in bulk is only obtained if the energy injection scales, due to the mutual generation of rotor translational dynamics throughout the system and the edge flows, are well separated. The combination of edge flow and entropic layering at the boundaries leads to oscillating hydrodynamic stresses and consequently to an oscillating vorticity profile. In the presence of odd viscosity, this consequently leads to non-trivial steady-state density modulations at the boundary, resulting from a balance of osmotic pressure and odd stresses. Relevant for the efficient dispersion and mixing of inert particles on the mesoscale by means of active turbulent mixing powered by rotors, a study of the dynamics of a binary mixture consisting out of rotors and passive particles is presented in chapter 7. Because the rotors are not self-propelled, but the translational dynamics is induced by the surrounding rotors, the passive particles, which do not inject further energy into the system, are transported according to the same mechanism as the rotors. The collective dynamics thus resembles the pure rotor bulk dynamics at the respective density of only rotors. However, since no odd stresses act between the passive particles, only mutual rotor interactions lead to odd stresses leading to the accumulation of rotors in the regions of positive vorticity. This density increase is associated with a pressure increase, which balances the odd stresses acting on the rotors. However, the passive particles are only subject to the accumulation induced pressure increase such that these particles are transported into the areas of low rotor concentration, i.e., the regions of negative vorticity. Under conditions of sustained vortex flow, this results in segregation of both particle types. Since local symmetry breaking can convert injected rotational into translational energy, microswimmers can be constructed out of rotor materials when a suitable breaking of symmetry is kept in the vicinity of a rotor. One hypothetical realisation, i.e., a coupled rotor pair consisting out of two rotors of opposite angular velocity and of fixed distance, termed a birotor, are studied in chapter 8. The birotor pumps the fluid into one direction and consequently translates into the opposite direction, and creates a flow field reminiscent of a source doublet, or sliplet flow field. Fixed in space the birotor might be an interesting realisation of a microfluidic pump. The trans- lational dynamics of a birotor can be mapped onto the active Brownian particle model for single swimmers. However, due to the hydrodynamic interactions among the rotors, the birotor ensemble dynamics do not show the emergence of stable motility induced clustering. The reason for this is the flow created by birotor in small aggregates which effectively pushes further arriving birotors away from small aggregates, which eventually are all dispersed by thermal fluctuations.

In this thesis I take a look at stochastic models for fitness landscapes, specifically the House-of-Cards (HoC) model of completely uncorrelated fitness values and the NK-type models which are built through combination of HoC landscapes as building blocks. These models are parameterized by a parameter k, which is considered to determined the "ruggedness" of the fitness landscape, with a maximal value of k corresponding to the HoC model and a value of k=1 corresponding to non-epistatic landscapes. I consider the behavior of two properties related to ruggedness on these landscapes, namely the number of local fitness maxima and the accessibility of genotypes via paths of monotonic fitness increase. Although high ruggedness is connected to a higher number of local maxima and therefore intuitively also a lower probability of distance genotypes being accessible from one another, this turns out to not hold generally. Contrary to assumptions made when the NK model was first introduced\autocite{weinberger1991}, it can be shown that asymptotic different quantitative results for the number of local maxima can be found for different choices of interaction structures between loci of the genotype. These models have analogous interpretations in solid state physics as the random energy model and spin glass models.

Die Diagnostik und Therapie der Hyponatriämie (HN) gestaltet sich, trotz der auch heute noch aktuellen, im Jahr 2014 publizierten European Best Practice Guideline (EBPG), problematisch. Die vorgeschlagenen diagnostischen und therapeutischen Algorithmen der Leitlinie sind komplex, basieren zu großen Teilen auf Expertenmeinung und wurden bislang nicht wissenschaftlich evaluiert. Ziel der durchgeführten Studie war es daher, den EBPG-Algorithmus auf seine diagnostische sowie die sich aus diesem Algorithmus ableitenden Empfehlungen auf ihre therapeutische Wertigkeit zu untersuchen. Darüber hinaus stellen wir zwei vereinfachte Algorithmen vor, die eine frühe Therapieentscheidung ohne genaue Kenntnis der zugrundeliegenden Ursache der Hyponatriämie ermöglichen sollen, und vergleichen diese mit Blick auf die zu erwartende Therapieeffektivität mit dem EBPG-Algorithmus: Algorithmus 1: Hypervolämie => Flüssigkeitsrestriktion, sonst NaCl 0,9% Algorithmus 2: Non-Hypervolämie und Kreatinin >1 mg/dl => NaCl 0,9%, sonst Tolvaptan Für die retrospektive Arbeit wurde eine Datenbank mit allen zwischen dem 01.01.2008 und dem 03.03.2013 stationär in der Uniklinik Köln behandelten Patienten mit einem Plasmanatriumwert von ≤125 mmol/L erstellt, die ausreichende Informationen (Klinik, Labor, Verlaufsbeurteilung) boten, um sicher die ätiologische Einordnung der Hyponatriämie zu erlauben und dementsprechend geeignete Therapieoptionen zu formulieren. Die zu untersuchenden Algorithmen wurden als SPSS-Skript hinterlegt und auf die Patienten somit ohne Untersucherbias angewandt. Durch ein Expertenpanel, bestehend aus erfahrenen Nephrologen der Uniklinik Köln, wurde anhand aller vorliegenden Informationen die Ätiologie und die initial sinnvollste Therapieoption für jeden Patienten festgelegt. Insgesamt konnten so 294 Fälle detektiert und sicher ätiologisch eingeordnet werden. Diese Klassifizierung wurde als Referenz bezeichnet. Der EBPG-Algorithmus zeigte eine schlechte diagnostische Overall accuracy mit einem Übereinstimmungswert von nur 53% mit der Referenz (Cohen’s kappa: 0,41). Vor allem gelingt es dem Algorithmus nicht, Patienten, mit einen Urinnatrium >30 mmol/L, die Diuretika einnehmen oder ein Nierenversagen haben, korrekt zu klassifizieren. Weiterhin kann ein erheblicher Anteil durch den Algorithmus per se nicht eindeutig klassifiziert werden. Entfernt man diese Kategorien aus der Analyse liegt die Overall accuracy immer noch nur bei 68% (Cohen’s kappa: 0,53). Darüber hinaus zeigt sich, dass logische Inkonsistenzen innerhalb des Algorithmus weitere diagnostische Unsicherheiten bedingen. Während die entsprechenden Therapieempfehlungen der EBPG lediglich in 62% mit den laut Expertenmeinung effektiven Optionen übereinstimmten, war das bei der Anwendung von Algorithmus 1 in immerhin 76% der Fall. Algorithmus 2 war nur geringfügig der EBPG-Empfehlung überlegen. Die Analyse der Patienten, die tatsächlich die von Algorithmus 1 vorgeschlagenen Therapien erhalten hatte, erbrachte tatsächlich zumindest bei den Patienten mit nicht-hypervolämischer Hyponatriämie (die NaCl 0,9% erhielten) eine gute Effektivität (88%), allerdings auch eine recht hohe Überkorrekturrate (25%). Die hier vorgelegten Ergebnisse geben Anlass, den vereinfachten Algorithmus 1 in einer prospektiven Untersuchung zu validieren.

Hintergrund. Heutzutage ist bereits bekannt, dass Kognitive Stimulation (KS) das Potenzial hat, die kog-nitive Leistungsfähigkeit bei Demenzpatienten zu verbessern und somit als vielversprechende Thera-piemöglichkeit bei kognitiven Beeinträchtigungen gesehen wird. Im Bereich der Parkinson‘s Disease Dementia (PDD) mangelt es bisher noch an aussagekräftigen Studien, sodass es schwer fällt, eine ein-deutige Empfehlung auszusprechen. Unsere Studie untersucht den Effekt von KS auf die globale Kogni-tion sowie die sekundären Outcomes Depression und Lebensqualität. Methoden. Für die Studie wurden 28 PDD-Patienten randomisiert entweder der Interventions- (KS; n=16) oder der aktiven Kontrollgruppe (Bewegungstherapie; n=12) zugeteilt. Die Probanden der Inter-ventionsgruppe erhielten über einen Zeitraum von acht Wochen jeweils zweimal wöchentlich für 60 Minuten eine Trainingseinheit (16 Übungseinheiten) mit dem kognitiven Stimulationsprogramm NEU-ROvitalis Sinnreich Parkinson‘s Disease (NV Sinnreich PD). Jeweils zeitnah vor, sowie im Anschluss an die Interventionsphase wurde eine elaborierte neuropsychologische Testbatterie durchgeführt. Hauptergebnisse. Wir fanden keinen Hinweis auf eine Verbesserung der globalen Kognition, der De-pressionswerte oder der Lebensqualität durch KS. Die Between-group Analyse, bei der die Differenzen der Prä- und Posttest-Werte verglichen wurden, zeigte eine Überlegenheit der Kontrollgruppe in Bezug auf globale Kognition (CERAD Total Score), Depression (GDS) und Lebensqualität (QoL-AD). Der Grup-penunterschied war jedoch nicht statistisch signifikant. Bei der Within-group Analyse fanden wir in der Interventionsgruppe eine leichte Verschlechterung der kognitiven Leistung und der subjektiv wahrge-nommenen Lebensqualität bei einem gleichbleibenden Depressionsniveau. In der Kontrollgruppe zeigte sich demgegenüber eine geringe Verbesserung der globalen Kognition sowie der depressiven Symptomatik. Die Lebensqualität blieb konstant. Insgesamt erreichte keines unserer Ergebnisse die Schwelle der statistischen Signifikanz. Schlussfolgerung. Obwohl anhand der Ergebnisse dieser Studie keine signifikanten Verbesserungen der Kognition, der depressiven Symptomatik oder der Lebensqualität aufgezeigt werden konnte, ist die Evi-denz für die Wirksamkeit von KS bei Demenzpatienten groß. Aus diesem Grund sollte KS auch weiterhin als vielversprechende Option in der PDD-Therapie gesehen werden. Zusätzliche Studien mit einer grö-ßeren Stichprobe und einheitlichen Einschlusskriterien sind nötig, um mögliche Effekte von KS bei PDD-Patienten weiter zu untersuchen.

Understanding how organisms adapt to new environments is a key goal of evolutionary biology. Populations subject to abrupt environmental change must adapt quickly to avoid extinction. Small populations are especially vulnerable to habitat changes, confronting high extinction risk due to limited genetic variation and low efficiency of selection. Theory predicts that the age of a population and its long- term effective size should influence adaptation and trait architecture. Here, we investigate the mechanisms of adaptation after a sudden shift to a more arid climate using natural populations of Arabidopsis thaliana in Cape Verde (CVI). CVI Arabidopsis is found on two islands (Santo Antão and Fogo) and represents diverged, monophyletic lineages based on the near absence of shared polymorphisms with each other or the continent. Time to flowering was reduced in parallel on the islands, causing a consequent increase in fitness, and allowing adaptation to the arid CVI. This change was mediated by convergent de novo loss of function of two core flowering time genes: FRI in Santo Antão and FLC in Fogo. Our results reveal a case where expansion of the new populations coincided with the emergence and proliferation of these novel variants, consistent with models of rapid adaptation and evolutionary rescue. We further contrast the genetic architecture of flowering time in the recently formed small Ne Arabidopsis lineages from Cape Verde with their much older, larger Ne progenitor – the Moroccan population. We find that polygenicity is severely reduced in the colonizing populations and effect sizes of candidate loci are exponentially distributed, consistent with fitness measures showing evidence for directional selection in the islands. In addition to the major effect variants FRI K232X and FLC R3X, we identify candidate variants from core flowering time pathways as well as those that indirectly affect flowering time, including nutrient processing and light sensing. Surprisingly we find no effect of the well- known Cvi-0-EDI (CRY2 V367M) variant in the natural population. Our results provide a particularly clear empirical example of the effect of demographic history has on trait architecture.

Männlich-gleichgeschlechtliche Sexualität war jahrhundertelang ein wichtiges Narrativ des Sexualdiskurses der arabischen Liebesdichtung. Im 19. Jahrhundert entstand durch den vermehrten Kontakt zu Europa mit der Nahḍa eine neue literarische Bewegung, durch deren Einfluss männliches gleichgeschlechtliches Begehren jedoch zunehmend aus der Dichtung verschwand. Dem Ambiguitätstoleranzkonzept von Thomas Bauer folgend wird die These aufgestellt, dass sich die ambiguitätstolerante arabische Welt durch westliche Einflüsse zu einer intoleranteren Gesellschaft entwickelt hat. Die vorliegende Arbeit widmet sich der Veränderung des Sexualdiskurses. Dabei stellen sich folgende Fragen: Welches Bild von männlicher gleichgeschlechtlicher Sexualität wurde jeweils von Orientalisten und Nahḍisten gezeichnet? Wie unterscheiden sich die Darstellungen voneinander? Wie haben sich diese Vorstellungen in der arabischen Literatur des 19. Jahrhunderts im Vergleich zur arabischen Vormoderne verändert? Anhand der sozialwissenschaftlichen Diskursanalyse werden für diese Untersuchung ausgewählte Textstellen aus den Hauptwerken von jeweils zwei Vertretern der Nahḍa und des orientalischen Reiseberichts bzw. der Orientalistik analysiert. Es zeigt sich, dass männliches gleichgeschlechtliches Begehren von beiden literarischen Strömungen negativ dargestellt wird. Die Darstellung in der orientalischen Reiseliteratur wird zudem, passend zu Saids Orientalismus-Theorie, ambivalent dargestellt. Die analysierten Autoren scheinen in ihren Werken unterschiedliche Ziele zu verfolgen: entweder, um das Selbst oder den Anderen als positiv oder negativ darzustellen.

Despite some notable counterexamples, the theoretical and empirical exchange between the fields of learning and memory is limited. In an attempt to promote further theoretical exchange, I explored how learning and memory may be conceptualized as distinct algorithms that operate on a the same representations of past experiences. I review representational and process assumptions in learning and memory, by the example of evaluative conditioning and false recognition, and identified important similarities in the theoretical debates. Based on my review, I identify global matching memory models and their exemplar representation as a promising candidate for a common representational substrate that satisfies the principle of least commitment. I then present two cases in which exemplar-based global matching models, which take characteristics of the stimulus material and context into account, suggest parsimonious explanations for empirical dissociations in evaluative conditioning and false recognition in long-term memory. These explanations suggest reinterpretations of findings that are commonly taken as evidence for dual-representation models. Finally, I report the same approach provides also provides a natural unitary account of false recognition in short-term memory, a finding which challenges the assumption that short-term memory is insulated from long-term memory. Taken together, this work illustrates the broad explanatory scope and the integrative and yet parsimonious potential of exemplar-based global matching models.

Dry eye disease (DED) has a high prevalence (up to 50% in some communities) with increasing incidence. Notably, patients have such high morbidity and burden that they desperately need effective treatment. However, as a "multifactorial disease," DED consists of various complex disorders, all of which interact to form a vicious circle and obscure the etiology. Even though physicians and patients have different therapeutic options, the common disadvantages in current treatments are (i) a lack of compliance due to an overload of products, (ii) the occurrence of side effects of different drugs, and (iii) limited efficiency in some particular cases. As a result, DED requires a novel therapy capable of simultaneously addressing multiple targets in DED pathogenesis. To find suitable targets and candidates for DED, the endocannabinoid system (ECS) and its receptors (CBRs) present at the ocular surface are a promising choice, as ECS functions are involved in a plethora of physical processes. Experimental evidence showed that using CBRs ligands can modulate anti-inflammatory, neurosensory, and wound-healing processes, which are potential to control and prevent DED pathogenesis and the vicious circle. Therefore, this study was carried out to determine whether CBR ligand eye drops can provide a multiple-target therapy for DED. The project hereby consisted of three parts, addressing consecutive objectives: Firstly, this study confirms the involvement of CBRs (in particular, CB1R and CB2R) in DED pathomechanism based on an experimental DED mouse model (desiccating stress model). CB1R and CB2R were detected by RT-qPCR and in-situ hybridization techniques in the cornea, conjunctiva, and lacrimal glands. During DED-induction, CB1R and CB2R expressions were increasing, concurrent with significant DED phenotypes (low tear production, high score of cornea epitheliopathy, and reduced cornea sensitivity). Furthermore, different CBRs ligands were topically applied to DED-induced mice. CBRs therapy suppressed the increasing trend of CBR expression, which coincided with improved phenotype readouts. Tetrahydrocannabinol (THC) is a promising candidate for anti-inflammatory effects, together with protecting nerve morphology and maintaining corneal sensitivity. Secondly, an in-vitro wound-healing model was developed to characterize the influence of CBR on the re-epithelialization process. Interestingly, while CB1R was found to have a significant effect, selective CB2R ligand did not influence the re-epithelialization. In detail, activating CB1R improved the wound-healing rate while selectively inhibiting CB1R delayed the wound-healing process. Furthermore, tetrahydrocannabinol (THC), a non-selective agonist, showed a biphasic effect: high concentration (from 1 to 10 µM) delayed wound healing, while low concentration (from 0.01 to 0.5 µM) increased the rate. This finding supports the functional role of CBRs in DED pathogenesis and management. Thirdly, we proposed two eyedrop formulations for THC, in which THC was formulated in the form of micelle in water at the nanoscale (around 10nm). All ingredients are already used in pharmaceuticals and bio-products, so the formulations are expected to be safe and well-tolerated. Additionally, the formulation steps are feasible with low technical complexity, showing promise for commercial scaling-up. The finally proposed formulation contains 0.5% THC, adequate to provide a significant effect, as shown in the in-vivo model in the first part. Also, the obtained results confirmed stability when stored at room temperature or refrigerator (4-8oC), facilitating its use by patients. In summary, this study confirmed the potentiality of CBR and CBR ligands, notably THC, as a multiple-target therapy for dry eye patients.