Radboud University Press is a unique department at Radboud University. We are a Diamond Open Access publisher of high-quality academic peer-reviewed books and journals across a wide range of disciplines for authors and editors affiliated with Radboud University. The ‘Diamond’ label means that we offer open-access publications free of charge for both authors and readers. Meeting the highest academic standards is our primary goal. Empowering our authors to fully retain their copyrights is our main principle.
This dissertation examines the relaunch and transformation of the European Commission’s Common Consolidated Corporate Tax Base (CCCTB) proposal in 2016. Initially introduced in 2011 as a voluntary, business-friendly framework for harmonizing EU corporate taxation, the CCCTB failed to gain political agreement. Its subsequent relaunch as a mandatory, anti–tax avoidance instrument marked a significant policy shift. Adopting a critical political economy perspective and employing the Historical Materialist Policy Analysis (HMPA) framework, this dissertation interprets EU tax policy as the outcome of a struggle between three competing hegemony projects: neoliberal, neomercantilist, and center-left. Drawing on expert interviews and extensive document analysis, four key explanatory factors for the CCCTB’s relaunch are identified: the post-crisis rise of a center-left project advocating tax justice; the enduring structural power of neoliberal forces that limits the possibilities for progressive change; member state budgetary and administrative concerns; and strategic action within the European Commission. Although center-left ideas reshaped the Commission’s framing of the CCCTB, persistent power asymmetries prevented its adoption, illustrating the structural constraints on progressive reform within EU corporate tax policymaking.
Copyright (c) 2025 Indra Römgens (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Improving the efficacy and patient tolerability of colorectal cancer screening
Colorectal cancer is a common disease, but early detection can prevent a great deal of suffering. This thesis investigated two major obstacles: the reliability of the current stool test and the burdensome preparation for a colonoscopy. In the first part, a breath test was evaluated that measures volatile compounds in exhaled air. The test was safe and simple for patients, but it was not yet accurate enough to replace the existing test. The second part focused on the discomfort of bowel preparation for a colonoscopy. Research showed that smaller amounts of laxatives can clean the bowel just as effectively. A 1-liter bowel preparation proved to be equally effective but much more comfortable than a 2-liter preparation. Additionally, a new flushing system that cleans the bowel during the colonoscopy was tested and appeared promising and feasible.
Copyright (c) 2025 Milou van Riswijk (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Dermatophyte adaptation to the human host exemplified by Microsporum
This dissertation is structured into 7 chapters, using M. canis as a model to investigate its evolutionary shift from animal hosts, such as cats and dogs, to human hosts and its dual role in infection and allergy. Each chapter explores a distinct aspect of M.canis infection, including its function as both a pathogen and an allergen, its epidemiology, host adaptation, molecular mechanisms of virulence, and spore germination.
Copyright (c) 2025 Xin Zhou (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Cardiovascular risk management for patients with a severe mental illness
This thesis explores the management of cardiovascular risk (CVR) in primary healthcare for patients with a severe mental illness (SMI) from the perspective of general practitioners (GPs) and develops an intervention to reduce CVR. Given that individuals with an SMI have a significantly reduced life expectancy due to heightened CVR, the study examines the role of GPs in mitigating these risks and the challenges they face. Findings indicate that CVR screening for SMI patients in Dutch primary care is inadequate, with only 8.5% of patients being screened in the absence of diabetes or cardiovascular disease. GPs express a sense of responsibility but lack awareness, confidence, and adequate collaboration with psychiatrists. To address these issues, the ‘Transmural collaborative care model for CVRM and medication review in patients using AntipsyChoTICs’ (TACTIC) was developed. This multidisciplinary intervention demonstrated promising feasibility, improving CVR outcomes in initial testing. However, challenges such as patient inclusion and adherence remain. The thesis recommends improving interdisciplinary collaboration, standardizing CVRM in guidelines, and incorporating lived experience perspectives. If proven effective in the upcoming trial, TACTIC could serve as a scalable, evidence-based model for integrating CVRM into primary care and reducing CVR-related mortality in SMI patients.
Copyright (c) 2025 Kirsti Jakobs (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Nederlandse franciscanen in Shanxi, China (1870-1953)
Deze omvangrijke studie beschrijft de geschiedenis van 117 Nederlandse franciscanen-missionarissen in de ruige Chinese provincie Shanxi in de periode 1871–1954. Op basis van duizenden persoonlijke en officiële brieven en artikelen uit missietijdschriften reconstrueert het boek hun leven. Het behandelt onder meer de motieven om het avontuur aan te gaan; de botsing tussen strikte franciscaanse kloosterregels en de noodzaak tot aanpassing aan lokale omstandigheden; de complexe verhouding met de missiebeweging in Nederland en Europa en het chronische gebrek aan mensen en middelen. Daarnaast laat het zien hoe de missionarissen samenwerkten met Chinese christenen en priesters, en vanaf 1922 met Nederlandse zusters, en hoe zij het werk overdroegen aan de Chinese clerus. Ten slotte plaatst het boek dit alles in de bredere politieke en sociale context van Shanxi en China: hongersnoden, opiumproblematiek, gewelddadige conflicten en toenemende buitenlandse inmenging.
Copyright (c) 2025 Jolanda Jansen (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Redefining T Cell Pathology in Connective Tissue Disorders
This thesis explores the role of autoreactive T cells—immune cells that mistakenly attack the body’s own tissues—in autoimmune diseases such as systemic sclerosis (SSc) and other connective tissue diseases (CTDs). These rare cells are difficult to detect, particularly in affected tissues and lymph nodes, but may hold the key to understanding how these diseases develop. To address this challenge, we developed an innovative toolkit that combines advanced imaging, state-of-the-art molecular techniques, and lab-based functional studies to track and analyze these cells in unprecedented detail. Our findings reveal that different types of autoreactive T cells play distinct roles in diseases like SSc and Sjögren’s syndrome (SjS). While SjS is primarily driven by helper T cells, SSc appears to be driven by cytotoxic effector T cells. These insights reshape our understanding of the immune system’s role in SSc and open the door to new diagnostic and therapeutic strategies. Notably, our studies targeting harmful cytotoxic T cells in early-stage SSc patients showed promise in reducing fibrosis—the most debilitating symptom of the disease. This work brings us closer to precision medicine tailored to the unique molecular fingerprints of each autoimmune CTD.
Copyright (c) 2025 Theogiannis Papadimitriou (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Patient participation in value-based healthcare
In this thesis, we explored how to improve patient participation within the context of VBHC. While previous studies have highlighted the challenges of patient participation and called for practical guidance, our research aimed to bridge this gap by offering concrete lessons and insights in individual and collective patient participation in the context of VBHC. Overall, our findings highlight opportunities to more fully integrate patient participation as an integral aspect of value improvement and care delivery. Based on the insights of the studies in this thesis, we derived five steps to help to ensure structural and meaningful patient participation in VBHC: 1. Ensure that preconditions for patient participation are met 2. Develop a strategy for patient participation 3. Prepare patients and staff for patient participation 4. Put patient participation into action 5. Evaluate patient participation with both patients and staff In conclusion, this thesis offers valuable lessons to improve patient participation. Wide adoption of these lessons contribute to healthcare improvements that genuinely reflect patient needs and preferences.
Copyright (c) 2025 Jet Westerink (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
How do socio-technical innovations shape the future of our societies and how can we steer innovation towards a specific direction? This thesis examines the policy-oriented practices that have come to the fore to answer these questions. Socio-technical change manifests in diverse directions and forms, with the science and politics of directionality emerging as a pivotal discourse shaping innovation policy. Although directionality facilitates interdisciplinary boundary spanning across economics, geography, political science, and sociology, its conceptual ambiguity persists. This dissertation scrutinizes the directionality discourse and examines, through three qualitative in-depth studies, how it is enacted through policy-oriented foresight practices. The research shows that behind the idea of purposefully directing innovation loom manifold situated deliberations in different arenas. These innovation direction debates provide insights into the social co-production and appraisal of innovation in the context of policy. Scrutinizing the formalized practices that bring about these debates, such as foresight, public engagement and their interactions with policy, allows for reconstructing the active integration of spaces, materials, know-how and meanings of directionality—an ever-evolving, arena-spanning process that lends itself as the title "directionality in the making". This process constantly articulates issues such as sustainability transitions, or, more recently, rearmament, as problems of innovation. In synthesizing the findings of the empirical case studies, the thesis elaborates on the role of foresight practices for directionality in the making. Ultimately, this contributes to understanding how legitimacy and reflexivity of innovation policy arrangements are produced.
Copyright (c) 2025 Max Priebe (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Hoe merk je aan mij dat ik een historicus ben?
In zijn inaugurele rede zet Harm Kaal zijn visie op het vakgebied van toegepaste geschiedenis uiteen. Toegepaste geschiedenis gaat over het gebruik van historische kennis, inzichten en vaardigheden in, en gericht op, het heden en de toekomst. Het begrip toegepaste geschiedenis is sterk verbonden met de context van overheidsbeleid en daarmee met de wereld van politiek en bestuur. Kaal staat stil bij vragen als: welke lessen kunnen we trekken uit het verleden om beleid in het heden en voor de toekomst te verbeteren? En: hoe kunnen we historische inzichten en vaardigheden beter verankeren in de beleidspraktijk?
Copyright (c) 2025 Harm Kaal (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
This thesis focuses on family care within palliative care. When people wish to die at home, the role of their close ones is crucial – yet often burdensome. Family care, however, is not purely about performing care tasks; it is also and primarily about values, (moral) dilemmas, and expectations. Especially considering the growing pressure on families due to societal changes, support for family caregivers is essential. Insight into the complex and normative nature of family care can help us better understand why people are often determined to care. To engage a broader audience, the graphic novel 'Naasten' (Dutch for: Loved ones) was developed together with comic artists. This interdisciplinary project yielded relevant insights for other researchers interested in using artistic methods. This thesis argues that, when carefully applied, and particularly within education, graphic novels like 'Naasten' can foster dialogue. Such dialogue is important, since family care can be both a disruptive and deeply valuable experience.
Copyright (c) 2025 Maaike Haan (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Semiclassical theory for quantum plasmons in two-dimensional inhomogeneous media
The rapid development of two-dimensional materials has spurred significant progress in quantum plasmonics, a field focused on manipulating light at the nanoscale using plasmons. These collective electron oscillations are promising for integrated photonic circuits due to their strong light interaction and ability to confine energy to subwavelength scales. However, predicting their behavior in realistic, inhomogeneous environments poses a significant theoretical challenge, as purely numerical methods are often limited to small system sizes. This thesis develops a novel semi-analytical theory to describe quantum plasmons in two-dimensional inhomogeneous media. Our approach is based on the semiclassical approximation within the Random Phase Approximation (RPA), which is applicable when the system's parameters vary smoothly over the length scale of the electron wavelength. By separating the in-plane and out-of-plane degrees of freedom, we derive an effective classical Hamiltonian that governs the plasmon dynamics. This derived framework provides an analytical handle on otherwise complex problems, fundamentally highlighting the duality of the semiclassical approximation: on one hand, the dynamics are described by classical trajectories, while on the other, the plasmon's wave-like nature is captured by the induced potential. The predictive power of this theoretical framework is demonstrated through three key applications. First, we analyze the scattering of plasmons from radially symmetric inhomogeneities, deriving a semiclassical expression for the scattering cross-section to describe how plasmons deflect and interfere. Second, we investigate plasmonic waveguides, identifying two distinct mechanisms for confinement: one based on total internal reflection, analogous to photonic waveguides, and another arising from quasi-localization, where local changes in the dielectric environment modulate the plasmon's amplitude. Finally, we study periodic structures (plasmonic crystals) and derive an analytical condition for the formation of a plasmonic band structure, which functions as an energy filter for propagating plasmons. Collectively, this research provides a comprehensive and fundamental framework for understanding and controlling plasmon dynamics in complex, inhomogeneous environments. It offers a crucial theoretical toolkit for the design and analysis of future plasmonic devices and technologies.
Copyright (c) 2025 Tjacco Koskamp (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
The Origin and Dynamics of the Thermosalient Phase Transition in the Molecular Crystal 4-DBpFO
This study aims to understand the mechanism and dynamics of the thermosalient structural phase transition in the molecular crystal 4-DBpFO. This transition is accompanied by a sudden and spectacular change in the crystal shape that makes the crystal jump over distances many times its size when it is heated across this transition. A variety of experimental techniques were used, including optical absorbance, fluorescence, linear birefringence, Raman spectroscopy and time-resolved pump-probe spectroscopy techniques, all as a function of temperature. The order parameter and lattice vibration modes responsible for the phase transition were identified by combining the experiment with molecular dynamics simulations results. In addition, strong THz pulses, resonant with the identified vibration modes, were used to trigger the phase transition.
Copyright (c) 2025 Xinyue Li (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
We develop the basic theory of stacky curves and their categories of sheaves, giving structure results for stacky curves and relating their sheaves to parabolic bundles. We classify the spherical stacky curves and construct a root system inside their Grothendieck Group. We thoroughly describe the geometry of the moduli stack of coherent sheaves on a stacky curve, resulting in several motivic statements, including a formula for the motive of the stack of vector bundles on a stacky curve. Finally we construct a projective good moduli space for the stack of semistable vector bundles on a stacky curve, by constructing determinantal line bundles with many sections on the moduli stack. There is an appendix generalizing global constructions for flattening stratifications to cyclotomic stacks and an appendix collecting techniques for the computation of motives.
Copyright (c) 2025 Lisanne Taams (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Biodiversity loss persists despite conservation efforts, prompting calls for transformative change—system-wide reorganizations across technological, economic, and social factors. This dissertation explores the role of landscape-oriented partnerships in enabling such change for biodiversity. These partnerships, which bring together governmental, private, and civil society actors, are examined through the lenses of transformative governance and discursive institutionalism. The first part of the dissertation assesses their governance strategies using a global scoping review and a case study of Nationaal Park Hollandse Duinen in the Netherlands. Findings reveal that while partnerships often employ integrative and inclusive governance, they rarely address indirect drivers of biodiversity loss or adopt more adaptive, transdisciplinary, and anticipatory approaches. The second part analyzes discursive and institutional conditions in the Dutch Dune and Flower Bulb Region, showing how dominant landscape discourses and amplification can limit the transformative potential of partnerships. Although partnerships can locally implement transformative goals, their potential remains limited without external policy support and complementary instruments. This research introduces a new framework for transformative landscape governance, which consists of holistic, emancipatory, and reflective governance approaches, that can help partnerships to enhance their transformative potential. It concludes that while landscape-oriented partnerships alone cannot drive systemic change, they can contribute as part of multi-level transformative governance mixes for biodiversity.
Copyright (c) 2025 Susan de Koning (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Exploring Relations and Graphs for Information Retrieval
Finding relevant information in a large collection of documents can be challenging, especially when only text is considered when determining relevancy. This research leverages graph data to express information needs that consider more information than just text data. In some cases, instead of using inverted indexes for the data representation in our work, we use database management systems to store data. First, we show that relational database systems are suited for retrieval experiments. A prototype system we built implements many proposed improvements to the BM25 ranking algorithm. In a large-scale reproduction study, we compare these improvements and find that the differences in effectiveness are smaller than we would expect, given the literature. We can easily change between versions of BM25 by rewriting the SQL query slightly, validating the usefulness of relational databases for reproducible IR research. Then, we extend the data model to a graph data model. Using a graph data model; we can include more diverse data than just text. We show that we can more easily express complex information needs with a corresponding graph query language than when a relational language is used. This model is built on top of an embedded database system, allowing fast materialization of output data and using it for further steps. One of the aspects we capture in the graph is information about entities. We use the Radboud Entity Linking (REL) system to connect entity information with documents. In order to efficiently annotate a large document collection with REL, we improved its efficiency. After these improvements, we used REL to create annotations for the MS MARCO document and passage collections. We can significantly improve recall for harder MS MARCO queries using these annotations. These entities are also used for an interactive demonstration where the geographical data of entities is used.
Copyright (c) 2025 Chris Kamphuis (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Our visual world is often complex and filled with different objects, usually more than we can process at once. To find relevant objects in such environments (e.g., apples in the supermarket or our bicycle at the train station), the visual system relies on an internal representation of the target object (an attentional model/template). For example, when we prepare to search for an apple, we reactivate visual neurons that are selective for red and round objects to facilitate their processing. Here, we investigated how these templates adapt to a predictable context. For example, to search for an apple, we might first look for the easy-to-find countertop where they are often found, and if it is surrounded by oranges, we might emphasize its unique color over its round shape. This demonstrates how a predictable environmental structure is learned and used for efficient search. However, holding an object in mind does not always facilitate visual processing. When we vividly imagine an object, it competes with the processing of similar objects when both activate the visual cortex simultaneously. Using multiple methods (behavioral tasks, EEG, eyetracking, and fMRI), this dissertation investigated how our internal representations are shaped by the external world and, in turn, shape what we perceive.
Copyright (c) 2025 Maëlle Lerebourg (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Ultrafast heat-assisted control of spins in ferrimagnetic dielectrics
This thesis investigates ultrafast optical control of spin dynamics in ferrimagnetic and canted antiferromagnetic dielectrics - materials that offer promising avenues for future optical data storage technologies. In particular, we study heat-assisted magnetic switching and all-optical control of magnetization, focusing on how these effects depend on laser parameters, temperature, and magnetic field. We begin by outlining the fundamental principles of magnetism and light-matter interaction, emphasizing magneto-optical and opto-magnetic effects. The experimental methods are based on time-resolved pump-probe techniques employing the magneto-optical Faraday effect with femtosecond resolution. We use magneto-optical diffraction of visible light to probe domain wall motion with nanometer spatial and sub-picosecond temporal resolution. In ferrimagnetic garnets, we analyze heat-assisted switching and identify a narrow range of conditions enabling recording-size precession amplitudes. Our simulations reveal that this regime corresponds to an optimal energy barrier between magnetic states. In orthoferrites, we explore coherent control of spin reorientation using double-pulse excitation. We identify temporal windows of spin insensitivity related to strong damping near the phase transition. Finally, we study the full polarization dependence of the switching, demonstrating that its dynamics defy simple additive behavior. These findings provide new insight into ultrafast spin control and support the development of THz-speed magneto-photonic devices.
Copyright (c) 2025 Alexander Dolgikh (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
On the predictive and explanative roles of deep neural networks in neuroscience
This dissertation investigates the application of deep neural networks (DNNs) in neuroscience, with an emphasis on the trade-off between predictive power and explanatory insight. The research highlights several key findings. First, a novel, unsupervised learning approach using an Adversarial Autoencoder (AAE) successfully detected early signs of epileptogenesis in EEG recordings, demonstrating the potential of DNNs for proactive diagnosis, even when labeled data is scarce. Second, experiments with Convolutional Neural Networks (CNNs) showed that they use spatial relationships between features for object recognition, especially with textureless images, but they do not capture the overall shape in a holistic manner. This finding helps us figure out how these models "see" and demonstrates a practical application of post-hoc model insight. Third, the research investigated what is more important for mimicking different parts of the visual cortex: the structure of the network or the training it receives. For the early visual area (V1), the inherent complexity of even randomly initialized networks was surprisingly effective in predicting responses, whereas higher-level areas (IT, VO) required specific training. This distinction shows how different brain regions may rely on different computational strategies, an insight gained through comparative use of the models and without a full explanation of the models themselves. In conclusion, this dissertation argues that DNNs are valuable tools in neuroscience, not only for predictions but also for gaining deeper insight. While the research acknowledges that complex models can be "black boxes," it emphasizes that careful validation allows us to use them effectively. These models can be powerful predictors (as in early disease detection) and, crucially, tools that help us generate new questions and expand our understanding of the brain.
Copyright (c) 2025 Amr Fouad Abdelhamid Farahat (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
In deze afscheidsrede blikt Peter-Arno terug op zijn carrière als taalwetenschapper en vakdidacticus. Vanuit een taalbeschouwing naar aanleiding van het woordje ‘tussen’ trekt hij lijnen door de hele taalwetenschap, de vakdidactiek en zijn persoonlijke loopbaan. Hij betoogt dat taal iets is tussen vorm en betekenis, en tussen individu en taalgemeenschap, wat je vanuit verschillende perspectieven kunt bekijken. In vakdidactische modellen gaat het vooral om de relatie tussen de onderdelen. Zo bespreekt hij een zelf ontwikkeld didactisch redeneermodel ter ondersteuning van taalbeschouwing. Ten slotte bekijkt hij in vogelvlucht zijn eigen loopbaan, die zich telkens vooral tussen verschillende disciplines afspeelde.
Copyright (c) 2025 Peter-Arno Coppen (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Net als alle andere levende wezens zijn wij, mensen, volledig afhankelijk van de natuur om ons heen. We kunnen simpelweg niet zonder. De natuur en het milieu staan echter onder hoge druk. Dat heeft alles te maken met de systemen die wij met elkaar hebben opgetuigd. Systemen die steeds complexer worden en tegelijkertijd de transitie naar een duurzame samenleving in de weg staan. In deze afscheidsrede wordt onderzocht hoe taal en communicatie kunnen bijdragen aan de realisering van een empathische samenleving waarin zorg voor elkaar en voor de natuur het uitgangspunt is. Like all other living creatures, we humans are totally dependent on the natural world around us. We simply cannot do without it. However, nature and the environment are under severe pressure. This is because of the systems we have set up. Systems that are becoming increasingly complex and at the same time hinder the transition to a sustainable society. In this farewell speech, it will be explored how language and communication can contribute to the realisation of an empathetic society in which care for each other and for nature is the key principle.
Copyright (c) 2025 Noelle Aarts (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
This inaugural lecture highlights how art, design and critical fashion practice expose the importance of moving beyond the transactional approach of the capitalist fashion industry. It focuses on two perspectives that deserve much more attention in the fashion and sustainability discourse. The first perspective builds upon post- and decolonial theories and highlights the importance of humbling the dominant Western, Eurocentric perspective of industrial fashion, in order to do more justice to the presence of multiple co-existing fashion systems and to affirm and activate a plurality of ways of making and wearing clothes. The second perspective focuses on humbling our perspective as human beings in relation to other species and nature. From a post-anthropocentric perspective, it proposes a practice of interspecies solidarity that helps to move beyond a human-centred focus where the human is superior to ecosystems in nature and/or to non-human entities. This inaugural lecture is a call to open up a pluriverse of fashion systems and solidary practices of making and wearing that have to do with being-with the world.
Copyright (c) 2025 Daniëlle Bruggeman (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Biomarker-driven immunotherapy for sarcoma
In this thesis we demonstrated the significant immunological and genomic heterogeneity between pAS and sAS, which has clear implications for patient tailored treatment strategies. Our findings support the universal distinction between AS subgroups based on etiology rather than anatomical location. We have prospectively shown that a subset of sAS patients, previously thought unlikely to benefit from ICI, can obtain durable responses to ICI treatment. In the current era of ICI and targeted therapies, identifying patients who are likely to respond to treatment is crucial to avoid subjecting non-responding patients to ineffective treatments and experiencing unnecessary toxicity. We have identified several predictive biomarkers associated with treatment response to ICI in AS, including T-cell density, TMB-H, the gut microbiome, and ctDNA levels. These findings allow for further exploration of these biomarkers in future clinical trials. Finally, based on the results of this thesis, we propose specific treatment strategies for future clinical trials, emphasizing the role of ICI in both advanced and (neo)adjuvant settings for sAS. Additionally, we recommend studies using combination therapies incorporating DDRi and ICI to enhance therapeutic efficacy. Our findings represent a significant step forward in the development of personalized, biomarker-driven treatment approaches, with the potential to improve patient outcomes and reshape therapeutic strategies for patients with rare sarcoma.
Copyright (c) 2025 Stefan van Ravensteijn (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
With this research, we aimed to increase our understanding of the role of AHR signaling in the formation and maintenance of the epidermal barrier. We focused on the regulation of keratinocyte proliferation and differentiation and investigated the potential of novel ligands as therapeutics to restore epidermal homeostasis in inflammatory skin diseases. Novel therapeutic ligands were analyzed in vitro and in vivo. We studied the capability of these AHR ligands in inflammatory skin models to restore aberrant keratinocyte differentiation and proliferation as well as dampen inflammatory signaling. To discover novel AHR-targeting therapeutics it is important to understand the mechanism behind AHR signaling. We studied the mechanism of AHR-driven keratinocyte differentiation and elucidated novel interaction partners through which the AHR directs terminal differentiation. We furthermore developed a method to knock out genes in a keratinocyte cell line using CRISPR/Cas9 as well as a novel method to measure skin barrier function. To assess the importance of AHR signaling in the inflammatory response of keratinocyte towards disease-associated cytokines, the effects of AHR activation upon experimental skin barrier defects in healthy human volunteers were investigated. The experimental studies point towards new molecular insights into AHR’s function in skin biology and underscore the potential of AHR ligands as a therapeutic modality in the treatment of inflammatory skin diseases.
Copyright (c) 2025 Noa van den Brink (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Rotational Dynamics in Colloidal Fluids, Crystals and Glasses
A colloid consists of a particle with at least one dimension between a few nanometers and a few micrometers dispersed in a solvent. Colloids are commonly found in nature, in opals, milk and even our blood as well as in industry in creams, gels and paints. Colloidal particles are useful for several key reasons. Firstly, by tuning their concentration they exhibit analogous phase behaviour to atoms and molecules. However, unlike atoms and molecules, colloidal particles can be viewed on a microscope. This allows us to study the dynamics of colloidal particles in a liquid, crystal (ordered solid) or a glass (disordered solid) phase. The study of the translational dynamics of colloidal particles has led to several important discoveries, none more so than the proof that atoms exist. However, the subject of this thesis, the rotational dynamics of colloidal particles, and the author’s homeland, Northern Ireland, have a striking similarity; they are both often overlooked but when considered become incredibly complex. This work demonstrates that the rotations of spherical colloidal particles can yield key insight into the impact of friction in colloidal materials and tell an intriguing story.
Copyright (c) 2025 Ruth Crothers (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
The temporal instability of cognitive performance
This thesis contributed to the empirical knowledge of cognitive variability through psychometric modeling of theory-based descriptive and mechanistic structures fitted to neural and behavioral data. We learned that cognitive variability is multidimensional: varying across tasks (Chapter 4) and timescales (Chapter 5). Chapter 3 taught us that, in a battery of response time tasks, cognitive variability is a correlate of inattention problems and is modulated by attentiveness as predicted by a noradrenergic mechanism. The results of Chapter 6 showed us that cognitive variability in a simple response-time task can be manipulated using methylphenidate, a transporter blocker of dopamine and noradrenaline. But contrary to prior hypotheses, the effect of methylphenidate could not be attributed to dopamine or a change in neural variability. Lastly, by examining the neural antecedents of cognitive variability, we learned that cognitive variability in a working memory task is driven by uncertainty in our encoded representations, which in turn depends on the neural resources spent to encode stimuli in the preceding trial (Chapter 7).
Copyright (c) 2025 Michael E. Aristodemou (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Filippina Fortuijn. Alexander van Geneve. Constantia van Bougies. Drie mensen die elkaar ongetwijfeld een keertje op straat zijn tegengekomen, ergens in de vroege jaren 1780. Alle drie woonden en werkten ze jarenlang in ’s-Hertogenbosch. Ze bezochten de wekelijkse markt, maakten praatjes met voorbijgangers en gingen op zondag naar de kerk. Net als hen leefden er vanaf de late zeventiende eeuw honderden anderen in de Brabantse stad, geboren in Suriname, Indonesië of een andere afgelegen plek in het uitgestrekte Nederlandse koloniale rijk. Om te begrijpen hoe zij in de stad terecht zijn gekomen, gaan we terug in de tijd. Stap voor stap ontrafelt dit boek hoe het kolonialisme de stedelijke bestuurders, bedrijven en gewone burgers uit ’s-Hertogenbosch verbond met de verste uithoeken van het Nederlandse rijk. Hoe slavernij niet slechts een verre werkelijkheid was, maar een onlosmakelijk onderdeel vormde van dit economische systeem. En hoe die slavernij, die zich afspeelde in Oost en West, gaandeweg ook zichtbaar werd in het straatbeeld van ’s-Hertogenbosch. Zo brengen we samen de vergeten verhalen van Filippina, Alexander en Constantia weer tot leven, en verweven we ze met de geschiedenis van de stad.
Copyright (c) 2025 Dries Lyna, Kim Lempereur, Joris Martens (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Opportunities in optimizing cytotoxic treatment of lung cancer in the era of immunotherapy
Based on the findings of this thesis, a series of evidence-based recommendations are proposed to optimize and personalize the dosing of carboplatin, pemetrexed, docetaxel, and atezolizumab in the treatment of advanced non-small cell lung cancer (NSCLC) patients.. For carboplatin, it is recommended to adopt cystatin C-based estimation of drug clearance. This approach incorporates patient-specific parameters including age, sex, body weight, and serum creatinine, and has shown superior accuracy and precision compared to traditional creatinine-based formulas like the Cockcroft-Gault formula in multiple prospective studies. For pemetrexed, standard dosing poses a high risk of toxicity in patients with impaired renal function (GFR <45 mL/min). It is advised that new treatment regimens be developed for this subgroup, alongside the incorporation of prophylactic folinic acid supplementation (45 mg, four times daily on days 2–15 of a 21-day cycle), modeled after established methotrexate protocols, to mitigate possible adverse effects. Regarding docetaxel, it remains a viable treatment option for advanced NSCLC patients previously treated with immunotherapy. However, hematological toxicity should not currently be used as a prognostic marker for survival outcomes. Further prospective research is required to clarify this potential association in the post-immunotherapy setting. For atezolizumab, personalized dosing intervals based on patient weight are recommended: 5 weeks for <50 kg, 4 weeks for 50–65 kg, and the standard 3 weeks for >65 kg. This strategy allows immediate clinical implementation and yields notable dose reductions up to 12% in European and 11.7% in U.S. populations, while retaining effective therapeutic exposure.
Copyright (c) 2025 Mart Pepijn Kicken (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Variational models for materials science
Materials science is a field that incorporates many branches of science, such as physics, chemistry, engineering, and, last but not least, mathematics. This dissertation specifically focuses on crystal growth and magnetism. We develop variational models to describe these two phenomena. The first line of research concerns thin films, whose relevance and production have been growing exponentially due to the increasing demand from electronic devices and many other applications. Among the countless ways a crystal can form, we investigate the case in which a crystalline material is deposited layer by layer onto a fixed crystalline substrate. If the atoms of the substrate at the interface occupy the natural lattice positions of the thin film, such crystal growth is called epitaxial. The second topic of this research concerns magnetic domain walls, which are regions where the magnetisation of a material transitions from one orientation to another. In particular, we study changes in magnetisation in domains with extreme geometries, such as dumbbell-shaped domains. The analysis of magnetisation behaviour in such geometries is relevant in micro- and nano-electronics applications, where the neck of the dumbbell serves as a model for magnetic contact points.
Copyright (c) 2025 Gabriele Fissore (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Educational reforms emphasise the importance of secondary school students learning to think critically about language. To this end, students must become aware that not every language problem has a single correct answer, but that an answer can be the result of a reasoning process in which the problem has been analysed from different perspectives. This doctoral research investigated whether the use of linguistic sources in grammar lessons could encourage students to explore language and develop their reflective thinking about language. To this end, King and Kitchener's (1994) Reflective Judgment Model was used to investigate what exactly reflective thinking is and how teachers feel about reflective thinking about language in secondary education. Next, the epistemic views of students on grammar were examined and how these differ from the views of experts. A model was then developed to enable students to investigate a language problem in small steps, using linguistic sources. This model was subsequently tested by teachers in the classroom using the Lesson Study method. The final study focused on the scaffolding that students need to develop their reflective thinking about language when consulting linguistic sources.
Copyright (c) 2025 Astrid Wijnands (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Task-dependent modulation of anticipatory attention
Thanks to attention, we can focus on the things that are important and filter out what is not important. Attention ensures that only what is important at this moment is fully processed. It is also possible to direct your attention to multiple things at the same time. A method introduced in 1988, called Multiple Object Tracking (MOT), has demonstrated this very well. In our own research, we use this MOT method to get an idea of where people focus their attention while tracking objects. Because all objects are identical, following and continuously distinguishing a subset of them (the targets) requires a tactical allocation of attention. We utilize the aforementioned spotlight function of attention to precisely map how it is distributed by briefly showing probes: tiny, difficult-to-detect dots. By combining MOT and probe detection, we have been able to visualize the distribution of attention in different situations using such a heatmap.
Copyright (c) 2025 Andrea Frielink-Loing (Author) https://creativecommons.org/licenses/by-nc-nd/4.0