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Alcohol Myopia and Gambling Behavior
No full textAlcohol and gambling are ubiquitous in our daily lives. In many movies for example that feature gambling, alcohol is often part of the scene, but gambling and alcohol often occur together in real life as well. Gambling is a popular pastime in parts of society, often in conjunction with alcohol consumption. A common assumption is that the consumption of alcohol makes risk behaviors such as gambling behavior more likely and leads to higher monetary stakes. Drawing on alcohol myopia theory (Steele & Josephs, 1990), stating that alcohol makes behavior more extreme depending on which cues are salient in the environment, I investigated whether acute alcohol intake fosters persistence in slot machine gambling when the high rewards of winning are salient but reduces persistence when the low chances of winning are salient. In an online study (Study 1), I developed a salience manipulation that was perceived as salient. In two more studies, participants consumed either alcohol (vs. a placebo) in the laboratory (Study 2) or I measured the blood alcohol content of bar patrons in the field (Study 3). Thereafter, participants gambled with a computerized slot machine on which I made either the high rewards or the low chances of winning salient by presenting eye-catching slogans. Making the high rewards salient led alcohol-intoxicated participants gamble more persistently, and making the low chances salient led them to gamble less persistently than sober participants. In Study 2, I also tracked participants’ eye-movements and found that intoxicated participants’ longer attention to the salient slogans mediated the effect of acute alcohol intake on more vs. less persistent gambling. Apparently, features of the gambling environment may enhance or reduce gambling in participants who consumed alcohol. Designing the gambling environment accordingly may be an effective nudge to reduce ongoing gambling
Komplexität und Abstraktion von Natur im ökonomischen Denken
No full textThis dissertation consists of three separate papers. Each constitutes an individual contribution to the role of complexity and the abstraction of nature in the history of economic thought. From the perspective of the philosophy of science and economics, different streams of thought emerging from the co-development of the social and natural sciences since the scientific revolution—evolving through the Enlightenment and the industrial revolution—can be identified. Fundamentally, these papers jointly argue that these streams reflect diverging conceptions of the nature of reality (ontological), which in turn inform different views on how knowledge can be acquired and how science should proceed.
While the organicist worldview understands the world as essentially complex, interrelated, dynamic, and organic, the mechanistic worldview interprets similar complexity as reducible to identifiable causalities open to modelling and quantification. The papers show that nature—understood as a highly complex and heterogeneous concept—resists much of the reductionist abstraction characteristic of the mechanistic tradition.
Through three case studies, the dissertation traces the trajectory taken by standard economics with respect to nature.
The first paper, Losing Ground: On the Marginalisation of Land in Economic Theory, surveys the literature for explanations of the declining role of land as a distinct factor of production. While external explanations such as changing class structures and the diminishing empirical relevance of land hold weight, the paper argues for a deeper, methodological cause. It identifies a “desire for analytical homogenisation” and shows how economists, working within a mechanistic paradigm, adopted simplification, formalisation, and abstraction to bypass the challenges posed by complexity—ultimately paving the way for the extreme mathematization of economics in the twentieth century.
The second paper, Keynes and the Preservation of Natural Beauty: Philosophical Foundations and a Natural Case for Planning, contextualises Keynes’s underappreciated advocacy for preserving rural England. This contribution to environmental history has received little attention. The paper shows that Keynes’s environmental concern was not incidental but rooted in a broader philosophical outlook. It identifies Keynes as indirectly aligned with the organicist tradition, critical of the formalism adopted by younger economists. This outlook informs his support for state planning and highlights his role as a philosophically grounded alternative to orthodox economics—a view echoed by later Post-Keynesian thinkers.
The third paper, Three Pioneers of (Social) Ecological Economics: On (Post) Keynesian Influences and the Intellectual Roots of E.F. Schumacher, Kenneth Boulding and Nicholas Georgescu-Roegen, situates modern ecological economics within the organicist tradition. Building on the ontological principles discussed in the first paper (via Marshall and Robinson) and the second (via Keynes), it explores the paradigmatic tensions within ecological economics itself. By examining the intellectual and personal connections between early ecological economists and Keynesian thinkers, it argues for ecological economics as a philosophically and ethically distinct alternative to mainstream economics.
Taken together, the three papers contribute to our understanding of how ontological commitments and methodological choices have shaped the treatment of nature in economic thought—and why revisiting these philosophical foundations remains relevant today. In addition, the dissertation offers several distinct contributions to the intellectual history of ecological economics and provides an original perspective on Keynes’s environmental thought that has so far remained unexplored.Diese Dissertation besteht aus drei eigenständigen Aufsätzen. Jeder von ihnen stellt einen individuellen Beitrag zur Rolle von Komplexität und zur Abstraktion von Natur in der Geschichte des ökonomischen Denkens dar. Aus der Perspektive der Wissenschafts- und Wirtschaftstheorie lassen sich unterschiedliche Denktraditionen erkennen, die seit der wissenschaftlichen Revolution und im Zuge von Aufklärung und industrieller Revolution aus der gemeinsamen Entwicklung von Sozial- und Naturwissenschaften hervorgegangen sind. Zusammen genommen argumentieren die Aufsätze, dass diese Strömungen unterschiedliche Auffassungen der Beschaffenheit der Realität widerspiegeln, aus denen wiederum divergierende Vorstellungen darüber entstehen, wie Wissen gewonnen werden kann und wie Wissenschaft betrieben werden sollte.
Während die organizistische Weltsicht die Welt als grundsätzlich komplex, vernetzt, dynamisch und organisch begreift, versteht die mechanistische Sichtweise ähnliche Komplexität als Ergebnis klar identifizierbarer Kausalitäten, die prinzipiell modellier- und quantifizierbar sind. Die Aufsätze zeigen, dass die Natur – als hochkomplexes und heterogenes Konzept verstanden – sich einem Großteil der reduktionistischen Abstraktion entzieht, wie sie für die mechanistische Tradition charakteristisch ist. Anhand von drei Fallstudien verfolgt die Dissertation die Entwicklung der Volkswirtschaftslehre im Umgang mit Natur.
Der erste Aufsatz Losing Ground: On the Marginalisation of Land in Economic Theory untersucht die Literatur nach Erklärungen für die abnehmende Bedeutung von Land als eigenständigem Produktionsfaktor. Während externe Faktoren wie der Wandel gesellschaftlicher Machtverhältnisse oder die sinkende empirische Relevanz von Land durchaus überzeugend sind, wird eine tiefer liegende methodologische Ursache herausgearbeitet. Der Beitrag identifiziert ein „Streben nach analytischer Homogenisierung“ und zeigt anhand verschiedener Episoden der Entstehung der orthodoxen Ökonomik, wie Ökonom*innen im Rahmen eines mechanistischen Paradigmas auf Vereinfachung, Formalisierung und Abstraktion setzten, um die Herausforderung von Komplexität zu umgehen– und damit den Weg für die starke Mathematisierung der Ökonomik im 20. Jahrhundert ebneten.
Der zweite Aufsatz Keynes and the Preservation of Natural Beauty: Philosophical Foundations and a Natural Case for Planning kontextualisiert Keynes’ bislang wenig beachtetes Engagement für den Erhalt des ländlichen Englands. Diese Episode der Umweltgeschichte wurde bisher kaum gewürdigt. Der Beitrag zeigt, dass es sich dabei nicht um eine Randnotiz in Keynes’ Denken handelt, sondern um ein Anliegen, das tief in seiner philosophischen Haltung verwurzelt ist. Keynes wird als Vertreter einer organizistischen Position erkennbar, der dem zunehmenden Formalismus jüngerer Ökonominnen kritisch gegenüberstand. Diese Haltung prägt sein Eintreten für staatliche Planung und macht sein Denken zu einer philosophisch fundierten Alternative zur aufkommenden Orthodoxie – eine Lesart, die später von Post Keynesianer*innen aufgegriffen und gestützt wurde.
Der dritte Aufsatz Three Pioneers of (Social) Ecological Economics: On (Post) Keynesian Influences and the Intellectual Roots of E.F. Schumacher, Kenneth Boulding and Nicholas Georgescu-Roegen verortet die moderne ökologische Ökonomik innerhalb der organizistischen Denktradition. Aufbauend auf den ontologischen Grundlagen, die im ersten Beitrag (über Marshall und Robinson) und im zweiten (über Keynes) entwickelt wurden, untersucht er die paradigmatischen Spannungen innerhalb der ökologischen Ökonomik selbst. Durch die Analyse intellektueller und persönlicher Verbindungen zwischen frühen ökologischen Ökonom*innen und keynesianischen Denker*innen argumentiert der Beitrag dafür, die ökologische Ökonomik als eine philosophisch und ethisch eigenständige Alternative zur Mainstream-Ökonomik zu begreifen.
In ihrer Gesamtheit leisten die drei Aufsätze einen Beitrag zum Verständnis davon, wie ontologische Überzeugungen und methodologische Entscheidungen die Behandlung von Natur in der ökonomischen Theorie geprägt haben – und warum eine Rückbesinnung auf diese philosophischen Grundlagen heute weiterhin relevant ist. Darüber hinaus liefert die Dissertation mehrere eigenständige Beiträge zur intellektuellen Geschichte der ökologischen Ökonomik und eröffnet eine bislang kaum beachtete Perspektive auf Keynes’ Umweltdenken
Engagement in Digital Health through Spatial Computing: Applications in Virtual Reality and Intelligent Virtual Agents
No full textEngagement is widely recognized as a critical determinant of success in serious games and digital health interventions, yet the term itself is often ambiguously defined and inconsistently operationalized, particularly in emerging domains such as Virtual Reality (VR)-based exergames, and applications employing Intelligent Virtual Agents (IVAs). With VR we refer to immersive, 3D-generated environments which can be experienced through Head-Mounted Displays (HMDs), while IVAs are essentially embodied Artificial Intelligence (AI) agents empowered by Large Language Models (LLMs). This dissertation investigates the multifaceted construct of engagement within Human-Computer Interaction (HCI), focusing on how digital interventions can be intentionally designed to foster and sustain user involvement, motivation, and positive experiences.
Motivated by demographic shifts, notably the increasing proportion of aging populations, and recent technological advances, including the availability of affordable VR headsets and breakthroughs in LLMs, digital health applications now reach wider audiences and offer new opportunities for both preventive and therapeutic use. However, maximizing their impact requires a deeper understanding of how to design for engagement across diverse user groups and contexts.
This work addresses two rapidly evolving areas: (i) the design and evaluation of VR-based exergames for older adults, and (ii) the development and deployment of IVAs as conversational partners in health-related interventions. Through a series of empirical studies, the dissertation explores strategies for promoting engagement, such as errorless learning paradigms to reduce early disengagement in exergames, and empathic feedback or adherence mechanisms in IVAs to foster trust, support, and sustained participation.
Key findings highlight the importance of iterative, Human-Centered Design (HCD) methodologies to accommodate the unique needs of older adults in VR systems, the trade-offs involved in balancing initial onboarding with opportunities for independent skill acquisition, and the challenges of ensuring reliability and empathy in IVAs, especially in sensitive health and therapeutic contexts. The studies also raise critical questions about the ethical deployment of these technologies, the risks of LLM-driven hallucinations, and the need for robust safeguards to preserve user well-being.
By combining the insights from case studies, behavioral psychology, and advances in IVAs, this dissertation contributes to a clearer understanding of engagement mechanisms and offers practical design recommendations for future digital health interventions. The results inform best practices for creating engaging, effective, and inclusive systems that can support health and well-being across diverse populations.Engagement wird als ein entscheidender Erfolgsfaktor in Serious Games und digitalen Gesundheitsinterventionen anerkannt. Dennoch wird der Begriff selbst häufig uneindeutig definiert und inkonsistent verwendet, insbesondere in aufkommenden Bereichen wie Virtual Reality (VR)-basierten Exergames und Anwendungen mit Intelligent Virtual Agents (IVAs). Mit VR sind immersive, 3D-generierte Umgebungen gemeint, die über HeadMounted Displays (HMDs) erlebt werden können, während IVAs im Wesentlichen verkörperte Artificial Intelligence (AI)-Agenten sind, die durch Large Language Models (LLMs) ermöglicht werden.
Diese Dissertation untersucht das vielschichtige Konstrukt des Engagements innerhalb der Human-Computer Interaction (HCI) und konzentriert sich darauf, wie digitale Interventionen gezielt gestaltet werden können, um Nutzerbeteiligung, Motivation und positive Erfahrungen zu fördern und aufrechtzuerhalten.
Getrieben von demografischen Veränderungen, insbesondere dem wachsenden Anteil älterer Bevölkerungsgruppen, sowie jüngsten technologischen Fortschritten wie der Verbreitung erschwinglicher VR-Headsets und Durchbrüchen bei LLMs, erreichen digitale Gesundheitsanwendungen mittlerweile ein breiteres Publikum und eröffnen neue Möglichkeiten für präventive und therapeutische Einsätze. Um jedoch ihre Wirkung zu maximieren, bedarf es eines tieferen Verständnisses dafür, wie Engagement für unterschiedliche Nutzergruppen und Kontexte gestaltet werden kann.
Diese Arbeit widmet sich zwei sich schnell entwickelnden Bereichen: (i) der Gestaltung und Evaluation von VR-basierten Exergames für ältere Erwachsene und (ii) der Entwicklung und dem Einsatz von IVAs als Gesprächspartner in gesundheitsbezogenen Interventionen. Anhand einer Reihe empirischer Studien untersucht die Dissertation Strategien zur Förderung von Engagement, etwa fehlerfreie Lernparadigmen, um frühzeitiges Aussteigen in Exergames zu reduzieren, sowie empathisches Feedback oder Mechanismen zur Einhaltung in IVAs, um Vertrauen, Unterstützung und nachhaltige Teilnahme zu stärken.
Zentrale Ergebnisse unterstreichen die Bedeutung iterativer, HumanCentered Design (HCD)-Methodologien, um den besonderen Bedürfnissen älterer Erwachsener in VR-Systemen gerecht zu werden, die Abwägungen zwischen anfänglichem Onboarding und Möglichkeiten zum eigenständigen Kompetenzerwerb, sowie die Herausforderungen, Zuverlässigkeit und Empathie in IVAs, insbesondere in sensiblen Gesundheits- und Therapiekontexten, sicherzustellen. Die Studien werfen zudem kritische Fragen zur ethischen Nutzung dieser Technologien, zu Risiken von durch LLMs verursachten Halluzinationen und zum Bedarf robuster Schutzmechanismen zur Wahrung des Nutzerwohls auf.
Durch die Kombination von Erkenntnissen aus Fallstudien, der Verhaltenspsychologie und Fortschritten bei IVAs leistet diese Dissertation einen Beitrag zu einem klareren Verständnis von Engagement-Mechanismen und bietet praxisnahe Gestaltungsempfehlungen für zukünftige digitale Gesundheitsinterventionen. Die Ergebnisse informieren über bewährte Vorgehensweisen zur Entwicklung ansprechender, wirkungsvoller und inklusiver Systeme, die Gesundheit und Wohlbefinden in diversen Bevölkerungsgruppen unterstützen können
Robuste Nutzung externer Information in der statistischen Analyse
No full textScientific research involves different processes, including the accumulation, aggregation, and cumulation of knowledge. The latter is construed by using existing theories and empirical findings to obtain new results based on previous ones in further research. In psychology, the accumulation and aggregation of knowledge is employed in everyday research. This thesis sheds light on the cumulation of knowledge in psychology by focusing on statistical cumulation – the use of quantitative external information in statistical analyses. To prevent new results from being biased by misspecified external information, the uncertainties of the external information should be considered. This includes estimation and structural uncertainty, as external quantities are estimates and there are often structural differences between a new data set and external sources, such as different designs or populations. Furthermore, this thesis discusses a wide range of approaches for incorporating external information and considers how well they reflect present uncertainties. Previous approaches include generalized Bayesian analyses and inferential models that incorporate partial prior information about a parameter of interest. Careful consideration of previous approaches indicates that a frequentist approach had not been developed for this purpose in psychology. To address this issue, this thesis introduces an externally informed generalized method of moments approach, which was developed and outlined across the four attached papers. Within this novel approach, two uses of external information are possible: improving the statistical analysis of new data and testing the fit of external information and data to indicate structural differences between them. Furthermore, this approach can incorporate external information about variables in the form of statistical moment equations. Thus, it is a relevant addition to existing methods as generalized Bayesian and inferential model approaches have difficulty incorporating this type of external information. The main focus of the four attached papers was on the application of the externally informed generalized method of moments approach to multiple linear and repeated measures generalized linear models. Additionally, this PhD project provides software that allows applied researchers to use the developed approach with various models, such as multiple linear models, repeated measures generalized linear models, two-level mixed linear models, and structural equation models
On Complex Spin Textures, Majorana Modes, and Machida-Shibata States - Exploring Nano-Scale Systems with Tight-Binding Models
No full textThe search for Majorana zero modes has been a major undertaking in the field of solid state physics in recent years, as they have potentially promising applications in fault-tolerant quantum computing. On the theory side, tight-binding models combining magnetism, Rashba spin-orbit coupling, and superconductivity have been on the forefront of this quest. They feature all ingredients necessary for experimental realization of Majorana zero modes. In this thesis, we take such a model, adapt and apply it to vastly different problems and geometries, while leaving its core intact. We explore its magnetic ground state in one and two dimensions, showing a surprisingly rich magnetic phase space. By self-consistently calculating the magnetic ground states before identifying electronic topological phases, we demonstrate in one dimension that, for a significant portion of the phase space, spin-spirals and topologically non-trivial states naturally coexist. We develop a computationally highly efficient approach to find the magnetic ground states of tight-binding models with a fitted classical spin model that is not inherently limited by assumptions, like RKKY being limited to weak magnetic couplings, and also grants additional insight into the driving magnetic forces of the system. With this method, we completely characterize the magnetic parameter space of our two-dimensional tight-binding model, showing that also 2D systems feature a rich magnetic phase diagram with many exotic magnetic phases despite the simplicity of the model at first glance. As the amount of data points is quite large and the magnetic phases are too complex to be classified by a simple algorithm, we employ an artificial neural network to classify the magnetic phases, thereby demonstrating that artificial neural networks can be a useful tool for the classification of magnetic ground states. Additionally, we provide theoretical support for the first experimental measurement of simultaneous zero-bias-peaks at both ends of an atomic chain, which marks a milestone in the search for Majoranas. In the experiment, an atomic Mn chain was constructed on Nb(110) in the [1¯10]-direction to build hybridizing Yu-Shiba-Rusinov states in a bottom-up approach. To model this, we adapt our tight-binding model to three dimensions. Replicating the experimental geometry, we are able to predict the chain length at which the found zero-modes are expected to evolve into isolated Majorana zero modes and demonstrate the crucial role of the strength of Rashba spin-orbit coupling. Finally, we provide a geometrically correct model for experiments on quantum dots caged by a box of Ag adatoms on a Ag island on superconducting Nb. With these experiments, the existence of energetically sharp non-magnetic in-gap states has been shown for the first time. This confirms theoretical predictions of Machida and Shibata on spin-degenerate Andreev bound states from 1972
Glykan-bindende Domänen als chimäre Antigenrezeptoren in der zellulären Immuntherapie pädiatrischer Leukämien
No full textIn der Therapie von Kindern mit refraktärer oder rezidivierter Leukämie stellen spezifische Immuntherapien wie eine Chimäre Antigen-Rezeptor (CAR)-T-Zelltherapie eine neuartige Behandlungsoption dar. Neben Proteinantigenen bieten sich dabei auch tumorspezifische Glykanstrukturen als neue Angriffspunkte an. Während die Bindungsspezifität von konventionellen CARs durch ein Antikörperfragment bedingt ist, wird in dieser Arbeit die kohlenhydraterkennende Domäne (CRD) von Lektinen in sogenannten LEC-CARs zur Erkennung von tumorassoziierten Kohlenhydratantigenen auf der Oberfläche von Leukämiezellen verwendet. Um neue Erkenntnisse über potentielle Glykane als Zielstrukturen für eine CAR-geleitete Immuntherapie zu gewinnen, wurde zunächst die Oberflächenglykosylierung von neun primären Leukämieproben mittels zehn verschiedenen rekombinanten humanen Lektinen (CD301, SRCL, DC-SIGN, Siglec2, Siglec3, Siglec4a, Siglec5, Siglec7, Siglec9, Siglec10) durchflusszytometrisch untersucht. Dabei wurde besonders die Bindung von SRCL auf adulten AML-Proben und von Siglec4a, Siglec7, Siglec9 und Siglec10 auf adulten und pädiatrischen Leukämieproben nachgewiesen. Dies deutet auf die Expression von Lewis X und eine Hypersialylierung von Oberflächenproteinen von Leukämiezellen hin. Um mögliche on target/off tumor-Effekte zu berücksichtigen, wurden zum Vergleich auch Zellen des hämatopoetischen Systems (peripheres Blut und Knochenmark) gesunder Spender bezüglich der Oberflächenglykosylierung analog untersucht. In der Gesamtschau dieser Glykosylierungsmuster von Leukämiezellen und gesunden Zellen wurden SRCL und Siglec7 als die vielversprechendsten Lektindomänen für die Generierung von LEC-CARs ausgewählt. Die CRDs von SRCL und Siglec7 wurden dafür an ein konventionelles CAR-Rückgrat der zweiten Generation (mit CD28 und CD3ζ) fusioniert. In dieser Arbeit wurde die Hypothese geprüft, ob die Kombination von zwei CRDs in einem Fusions-LEC-CAR die Spezifität und zytotoxische Effektivität im Vergleich mit LEC-CARs mit monomerer CRD steigern kann. Dafür wurden neben den einzelnen LEC-CARs auch die CRDs von SRCL und Siglec7 in einem Tandem-CAR-Konstrukt fusioniert. Nach viraler Transduktion von NK92-Zellen mit den LEC-CARs wurden diese hinsichtlich ihrer Oberflächenlokalisation und Bindungseigenschaften evaluiert und hinsichtlich ihrer Spezifität und Effektivität gegenüber Leukämiezelllinien in Bezug auf Zytotoxizität, Degranulation und IFNγ-Produktion untersucht. Obwohl die Fusions-LEC-CARs und der Siglec7 LEC-CAR spezifisch auf der NK92-Zelloberfläche nachgewiesen werden konnten, zeigte sich keinerlei funktionelle Aktivität gegenüber verschiedenen Leukämiezelllinien. Der SRCL LEC-CAR hingegen konnte seinen Liganden Lewis X spezifisch binden, lysierte die Lewis X-positiven Leukämiezelllinien Molm13 und HL-60 und die Lewis X-positive Brustkrebszelllinie KPL-1, jeweils mit begleitender Degranulation und IFNγ-Freisetzung. Diese Arbeit zeigt mit dem SRCL LEC-CAR eine neue Option für die Therapie von Lewis X-positiven Leukämien auf – mit potentieller Ausweitung auch auf solide Tumorentitäten.Specific immunotherapy such as chimeric antigen receptor (CAR)-T cell therapy is a new treatment option for children with relapsed and refractory leukemia. Besides protein-epitopes tumor-associated carbohydrate antigens (TACAs) also offer a possibility for CAR-T cells to attack cancer cells. Whilst the antigen specificity of conventional CARs results from an antibody fragment, in this work the carbohydrate recognition domain (CRD) of lectins is used in so-called LEC-CARs to specifically bind TACAs on leukemia cells. To gain new insights into TACAs that could serve as a target for CAR-T cell therapy, the surface glycosylation profile of nine primary leukemia samples was studied by flow cytometry using ten recombinant human lectins (CD301, SRCL, DC-SIGN, Siglec2, Siglec3, Siglec4a, Siglec5, Siglec7, Siglec9, Siglec10). The analysis showed that SRCL was able to bind to adult AML samples and Siglec4a, Siglec7, Siglec9 and Siglec10 to adult and pediatric leukemia samples. This indicates the expression of Lewis X and hypersialylation on the surface of leukemia cells. Overlapping glycan expression between normal and leukemia cells can cause relevant adverse reactions and therefore the surface glycosylation profile of normal hematopoietic cells (peripheral blood mononuclear cells and hematopoietic stem cells) was analogously analyzed. Keeping the results of overlapping glycan expression in mind, SRCL and Siglec7 were chosen as the most promising lectin domains for generating LEC-CARs. The CRDs of SRCL and Siglec7 were fused to a conventional second-generation CAR-backbone (with CD28 und CD3ζ). In this work the hypothesis was tested that the specificity and cytotoxic efficacy may be increased by combining two CRDs in comparison with only using one CRD in a LEC-CAR. Therefore, combinatorial LEC-CARs (tandem CARs) using the CRD of SRCL and Siglec7 were generated in addition to the LEC-CARs using the monomeric CRD. After viral transduction of NK92 cells with the LEC-CARs, analysis of the surface localization and binding properties of these receptors were performed. LEC-CAR expressing NK92 cells were also tested for their specificity and efficacy against leukemia cells regarding cytotoxicity, degranulation and production of IFNγ. Despite the proven localization of combinatorial LEC-CARs and Siglec7 LEC-CAR on the surface of NK92 cells cytotoxic activity of the expressing effector cells against leukemia cells could not be shown. Contrarily, SRCL LEC-CAR expressing NK92 cells were able to specifically bind Lewis X, to kill the Lewis X-expressing leukemia cell lines Molm13 und HL-60 and the Lewis X-expressing breast cancer cell line KPL-1, accompanied by significantly increased degranulation and production of IFNγ. This work shows that SRCL LEC-CAR is a new option for therapy of Lewis X-expressing leukemia and also potentially of solid tumors
Development of a structure-preserving idealized stochastic climate model
No full textThis thesis investigates an idealized two-dimensional stochastic climate model consisting of coupled atmospheric and ocean components. The atmospheric component incorporates stochasticity using the stochastic advection by Lie transport (SALT) approach, while the ocean component remains deterministic. The model serves as a tool to study fundamental processes arising from ocean-atmosphere interactions and to quantify the uncertainty induced by unresolved small-scale dynamics.
We conduct numerical simulations of the climate model to evaluate the effectiveness of SALT in representing the impact of unresolved dynamics on large-scale flow behavior. Our methodology consists of three stages. First, we develop numerical schemes for the ocean component. Next, we perform a numerical investigation of an idealized stochastic atmosphere model. Finally, we combine these approaches to solve the full stochastic climate model. Additionally, we present numerical simulations of stochastic incompressible Navier-Stokes equations.
The stochastic noise terms are estimated using synthetic data from high-resolution deterministic simulations. While the temporal component of noise is typically modeled using a Gaussian process, we also explore an alternative approach based on Ornstein–Uhlenbeck (OU) processes. The latter method results in smoother temperature and vorticity fields and enhances uncertainty quantification performance.
Our results demonstrate that ensemble forecasts from the stochastic climate model exhibit good reliability, with ensemble spread proportional to the ensemble root mean square error over a significant time window. Comparisons between the stochastic and deterministic model forecasts, initialized from randomly perturbed initial conditions, reveal that the stochastic approach consistently outperforms the deterministic one throughout the simulation period. Overall, our findings indicate that (1) SALT parameterization improves ensemble performance and (2) modeling temporal noise with an OU process instead of a Gaussian process enhances prediction quality
Pathways Linking Socioeconomic Position and Malarial Infection and Healthcare-Seeking Behaviour for Suspected Malaria in Sub-Saharan Africa
No full textMalaria remains a leading cause of morbidity and mortality, with an estimated 249 million infections and 608,000 deaths recorded in 2022 alone. Over 94% of these cases and deaths occurred in sub-Saharan Africa (SSA). Despite progress in malaria prevention and control in SSA over the past two decades, socioeconomic disparities in malaria incidence and healthcare-seeking behaviour for febrile illnesses persist both at regional and national levels.
This thesis is structured around three main components. First, a systematic review was conducted to examine the pathways linking poverty and malaria in SSA, focusing on studies that used mediation analysis, or reported changes in the coefficients of potential mediating variables in models adjusted for socioeconomic position (SEP) and mediators. The review appraised the mediation methods used and highlighted their strengths and limitations (Paper I). In Paper II, we used a regression-based counterfactual approach to mediation analysis in order to investigate the structural mechanisms driving socioeconomic disparities in P. falciparum infection, drawing on secondary data from two large cross-sectional studies conducted in the Southern region of Malawi during the dry and rainy seasons of 2014. This analysis presented the total natural direct effects (TNDEs) of SEP, the total natural indirect effects (TNIEs) through the mediator(s), and the proportion mediated (PM). In Paper III, we assessed the association between socioeconomic factors – SEP, maternal educational attainment and urban residence – and timely healthcare-seeking and diagnostic testing in children under five with febrile illness. A random-effects meta-analysis was conducted, using prevalence ratios (PRs) and standard errors from 16 nationally representative surveys conducted between 2018 and 2023. We also examined the mediating role of health facility type in the association between SEP and diagnostic testing.
In the systematic review (Paper I), we identified mediators, such as improved food security, better housing quality, and previous antimalarial use, while factors such as secondary or higher education of maternal/household head, use of long-lasting insecticide treated nets (LLINs), better nutrition, and indoor residual spraying were suggested as potential protective mediators based on changes in coefficients. In paper II, using data from cross-sectional surveys conducted in Malawi, housing (TNIE, OR =0.54, 95%CI 0.49 – 0.63) and educational attainment of the household head (TNIE, OR = 0.73, 95%CI 0.67 – 0.81) were identified as mediators of the association between SEP and P. falciparum infection during the rainy season. During the dry season, housing (TNIE, OR = 0.63, 95%CI 0.59 – 0.64), educational attainment (TNIE, OR = 0.70, 95%CI 0.62 – 0.71) and LLIN use (TNIE, OR = 0.88, 95%CI 0.85 – 0.94)
were important mediators. In Paper III, the results of the meta-analysis revealed that only 58.3% of febrile children received timely healthcare, and 38.2% underwent diagnostic testing. Higher SEP was associated with timely healthcare-seeking (PR = 1.18, 95%CI 1.11 – 1.25) and diagnostic testing (PR = 1.15, 95%CI 1.03 – 1.28). Higher maternal education was associated with timely healthcare-seeking in countries with malaria incidence ≥ 300 per 1,000 persons (PR = 1.11, 95%CI 1.01 – 1.23). Urban residence did not play a role in healthcare-seeking and diagnostic testing. The type of healthcare attended mediated the effect of SEP on diagnostic testing, with hospital visits (versus primary care) being associated with a higher likelihood of receiving diagnostic testing in 14 of 15 surveys.
The findings presented clearly show that the socioeconomic situation of a population is significantly associated with malaria risk, with evidence on the mediating factors being particularly useful in guiding policy and programs on where to focus their efforts. Key priorities should include improving housing conditions, enhancing education or malaria prevention awareness and training, in combination with ensuring widespread distribution and correct use of LLINs to reduce malaria infection rates. Additionally, the socioeconomic inequalities in healthcare-seeking behaviours highlight the need for targeted efforts to mitigate barriers to healthcare access, such as providing subsidies to families with low SEP. Finally, improving diagnostic supplies and the quality of primary care services can significantly improve diagnostic testing and timely appropriate care for children with febrile illnesses
A homotopy-coherent calculus of lax matrices
No full textThis thesis consists of two chapters, together with two supporting appendices. The first chapter describes the construction of a homotopy-coherent calculus of lax matrices. The second chapter gives a construction of a lax monoidal structure on the functor implementing pull-push of local systems along spans of infinity-groupoids. The first appendix shows that the notion of internal left Kan extension can be captured by horn filling conditions, and the second proves a formula for reflective localization in terms of spans
Nanoscale Engineering of Hybrid Graphene Architectures for Tailored Light-Matter Interactions Across the Microwave Spectrum
Get PDFGraphene is an exceptionally versatile material, renowned for its robustness, strong light-matter interactions and high electrical conductivity. It can even acquire superconducting properties through proximity effects with superconducting electrodes or by stacking two layers of graphene with a relative twist angle of 1.1°. The incorporation of graphene into hybrid device architectures combining superconducting and high-frequency circuit elements enables parametric amplification, single-photon detection and innovative qubit designs. At the same time, these components open new pathways to investigate the fundamental properties of graphene.
In this thesis, various complex graphene devices are engineered by integrating van der Waals materials, superconductors, and high-frequency circuits into hybrid architectures to explore light-matter interactions. Lithographic techniques were optimized to create micro- and nanostructured samples comprised of exfoliated as well as large-area, polycrystalline graphene. Tailored for the investigation of light-matter interactions, these devices provide a versatile platform to study the charge carrier transport in graphene under electromagnetic radiation in the microwave spectrum. Radio-frequency and microwave signals used in low-temperature magnetotransport measurements revealed signatures of nuclear spin effects in isotopically purified 13C graphene. To enhance the coupling efficiency of the radiation, hybrid circuits integrating large-area and exfoliated graphene with high-frequency waveguides were engineered for microwave spectroscopy experiments. However, the absence of resonant features in experiments suggests that an unknown mediator facilitating momentum transfer in electron spin resonance may be missing in pristine graphene.
Fabricating superconducting electrodes for graphene-based Josephson junctions (JJs) with sufficient electrical transparency to graphene proved technologically challenging and necessitated the substitution of niobium with titanium-aluminum. Under small magnetic fields, these aluminum-graphene junctions exhibited quantum interference effects that are attributed to Tomasch and McMillan-Rowell oscillations. These advancements in device performance pave the way for the integration of graphene JJs into superconducting microwave circuits, holding tremendous potential for quantum technologies, dark matter axion search and advanced photosensing applications.
In an alternative approach for light-matter interaction in a different spectral regime, asymmetric metallic grating gates on top of high-quality graphene structures enabled the rectification of sub-THz-radiation via plasmonic excitations. The photoresponse of these detectors is influenced by the incident frequency, temperature, and doping in the graphene channel, with their sensitivity estimated to be in the order of 10-12 W/Hz1/2.Graphen ist ein äußerst vielseitiges Material, bekannt für seine Robustheit, starke Licht-Materie-Wechselwirkungen und hohe elektrische Leitfähigkeit. Es kann sogar supraleitende Eigenschaften erlangen, etwa mittels Proximity-Effekt mit supraleitenden Elektroden oder durch das Anordnen zweier Graphenschichten mit einem relativen Rotationswinkel von 1,1°. Die Einbindung von Graphen in hybride Architekturen, die supraleitende und hochfrequente Schaltungselemente kombinieren, ermöglicht parametrische Verstärkung, Einzelphotonendetektion und innovative Qubit-Designs. Gleichzeitig stellen diese Komponenten neue Möglichkeiten zur Erforschung der grundlegenden Eigenschaften von Graphen dar.
In dieser Arbeit werden vielfältige Graphen-Devices durch die Integration von van derWaals-Materialien, Supraleitern und Hochfrequenzschaltungen in hybride Architekturen entwickelt, um Licht-Materie-Wechselwirkungen zu untersuchen. Lithografische Techniken wurden optimiert, um Mikro- und Nanostrukturen herzustellen, die sowohl aus exfoliertem als auch aus großflächigem, polykristallinen Graphen bestehen. Diese sind auf die Untersuchung von Licht-Materie-Wechselwirkungen zugeschnitten und bieten eine vielseitige Plattform zur Untersuchung des Ladungsträgertransports in Graphen unter elektromagnetischer Strahlung im Mikrowellenspektrum. Tieftemperaturmessungen mit Radiofrequenz- und Mikrowellensignalen bei hohen Magnetfeldern zeigten Anzeichen von Kernspineffekten in isotopenreinem 13C Graphen. Um die Einkopplung der Strahlung zu verbessern, wurden hybride Schaltungen für Experimente der Mikrowellenspektroskopie entwickelt, die großflächiges und exfoliertes Graphen mit hochfrequenten Wellenleitern kombinieren. Das Fehlen von Resonanzen in den Experimenten deutet auf einen unbekannten Mechanismus hin, welcher den Impulsübertrag für Elektronenspinresonanz erleichtern könnte, jedoch in reinem Graphen fehlt.
Die Herstellung supraleitendender Elektroden für graphenbasierte Josephson Kontakte (engl. Josephson junctions, JJs) mit ausreichender Transparenz erwies sich als technologisch herausfordernd, weshalb Niob durch Titan-Aluminium ersetzt werden musste. Bei kleinen Magnetfeldern zeigten diese Aluminium-Graphen-Kontakte Quanteninterferenzeffekte, die auf Tomasch- und McMillan-Rowell-Oszillationen zurückzuführen sind. Die dargestellten Fortschritte in der Deviceperformance ebnen den Weg für die Integration von Graphen-JJs in supraleitende Mikrowellenschaltungen, welche ein enormes Potenzial sowohl für Quantentechnologien, der Suche nach dunkler Materie und für neuartige Photodetektoren bieten.
Asymmetrische metallische Gitterelektroden auf hochqualitativen Graphenstrukturen stellen einen alternativen Ansatz dar, um Licht-Materie-Wechselwirkungen in einem anderen Frequenzbereich mittels plasmonischer Anregungen zu erforschen. Das Detektorsignal wird von der einfallenden Frequenz, Temperatur und Dotierung im Graphen beeinflusst, wobei ihre Empfindlichkeit auf etwa 10-12 W/Hz1/2 geschätzt wird