In this thesis, I focused on studying the above- and belowground interactions of J. vulgaris from a plant-soil feedback (hereafter, PSF) perspective. I investigated the temporal variation of... Show moreIn this thesis, I focused on studying the above- and belowground interactions of J. vulgaris from a plant-soil feedback (hereafter, PSF) perspective. I investigated the temporal variation of negative PSF and examined the effects of root-associated bacteria on plant performance and aboveground herbivores. Additionally, I tested the role of PSF in relation to plant population structure and the significance of soil legacy effects in natural conditions. The findings reveal that temporal dynamics in PSF are driven by changes in plant sensitivity and in the soil microbiome. Although bacteria isolated from J. vulgaris roots can negatively affect plant performance, they can also affect aboveground herbivores and other plant species. Consequently, these bacteria may not be suitable for biological control of J. vulgaris. Moreover, I discovered that soil nematodes can mediate plant-plant interactions, but often favoring J. vulgaris. In my field work, I detected soil legacy effects, but seedling recruitment spatial patterns of J. vulgaris were not soil-mediated. The insights gained from studying PSF and above- and belowground interactions have the potential to reshape traditional approaches employed in controlling invasive plants. This thesis emphasizes the importance of transitioning PSF experiments from indoor to outdoor settings considering various influencing factors simultaneously. Show less
Cancer immunotherapies utilizing immune checkpoint blockade (ICB) therapy targeting CTLA-4 and PD-1/PD-L1 relieve tumor-induced immune suppression and induce durable tumor regression. The use of... Show moreCancer immunotherapies utilizing immune checkpoint blockade (ICB) therapy targeting CTLA-4 and PD-1/PD-L1 relieve tumor-induced immune suppression and induce durable tumor regression. The use of ICB therapy have demonstrated remarkable therapeutic efficacy in a proportion of patients with melanoma. However, still a substantial percentage of patients does not respond (durable) to ICB treatment and many questions remain. Therefore, in this thesis, the aim is to improve our understanding of ICB efficacy. We demonstrate the promise of neoadjuvant ICB therapy (approach in which ICB therapy is applied before surgery) and analyze different cohorts of melanoma patients. This results in the identification of several markers that are associated with prognosis, including IFN-y related gene signature score, Batf3 dendritic cell associated gene signature score, tumor mutational burden and systemic LRG1 expression. These markers can potentially be targeted and might facilitate rational combination therapies that can boost the efficacy of ICB therapy. For this purpose, we perform a repurposing compound screen that targets antigen cross-presentation. Togethers, this work increases our understanding of factors that determine ICB therapy efficacy and toxicity, with the goal to identify novel strategies to improve outcome of melanoma patients in a rationale and personal manner. Show less
In this thesis we examined patient readiness for shared decision making (SDM) about treatment. We first assessed associations between patient-related characteristics and the occurrence of SDM.... Show moreIn this thesis we examined patient readiness for shared decision making (SDM) about treatment. We first assessed associations between patient-related characteristics and the occurrence of SDM. Overall, we did not find consistent associations between characteristics such as age or education level, and the extent to which SDM occurred (measured from the perspective of patients, clinicians, or observers). Second, we assessed what patients need to be ready, i.e., enabled and well-equipped, to participate in SDM about treatment. We identified a wide range of skills, cognitions, and emotions. For instance, patients need to be able to understand the relevant information, be able to and dare to express themselves in consultations with clinicians, and experience an adequate amount of time to talk to clinicians and to consider the options. Finally, we developed a questionnaire, the ReadySDM. The aim of the ReadySDM is to retrospectively measure the extent to which patients felt ready for SDM during a treatment decision-making process. The questionnaire has the potential to identify novel insights into patients’ support needs and ways to enhance SDM in daily practice. Show less
De Wet open overheid (Woo) is op 1 mei 2022 in werking getreden. Dit is de eerste uitspraak over de vraag of er op grond van de Woo een verplichting bestaat om documenten te vervaardigen. Het korte... Show moreDe Wet open overheid (Woo) is op 1 mei 2022 in werking getreden. Dit is de eerste uitspraak over de vraag of er op grond van de Woo een verplichting bestaat om documenten te vervaardigen. Het korte antwoord daarop is nee. In deze annotatie wordt eerst de casus en het oordeel van de Afdeling weergegeven. Vervolgens wordt op het oordeel van de Afdeling gereflecteerd in het licht van de roep om een responsiever bestuursrecht en de vraag of verzoeker een andere laagdrempelige wijze had om het gevraagde register te krijgen. Show less
Jong, K. de; Douglas, S.; Wolpert, M.; Delgadillo, J.; Aas, B.; Bovendeerd, B.; ... ; Barkham, M. 2024
This thesis focuses on data found in the field of computational drug discovery. New insight can be obtained by applying machine learning in various ways and in a variety of domains. Two studies... Show moreThis thesis focuses on data found in the field of computational drug discovery. New insight can be obtained by applying machine learning in various ways and in a variety of domains. Two studies delved into the application of proteochemometrics (PCM), a machine learning technique that can be used to find relations in protein-ligand bioactivity data and then predict using a virtual screen whether compounds that had never been tested on a particular protein, or set of proteins. With this, sets of compounds were suggested for experimental validation that were significant in a myriad of ways. Another study investigated the mutational patterns in cancer, applying a large dataset of mutation data and identifying several motifs in G protein-coupled receptors. The thesis also contains the work done on the Papyrus dataset, a large scale bioactivity dataset that focuses on standardising data for computational drug discovery and providing an out-of-the-box set that can be used in a variety of settings. Show less
The sequence-dependence of biomolecular interactions involving nucleic acids and proteins is essential for numerous processes inside the cell. Insights into the underlying molecular mechanisms have... Show moreThe sequence-dependence of biomolecular interactions involving nucleic acids and proteins is essential for numerous processes inside the cell. Insights into the underlying molecular mechanisms have been obtained using various biochemical and biophysical methods on two different levels — bulk and single-molecule. These have complemented each other as single-molecule studies excel in observing multi-state dynamic interactions, but perform only at low throughput; while bulk studies can probe many different sequences simultaneously, but providing limited kinetic information. To unite the strengths of both levels, we developed high-throughput Single-molecule Parallel Analysis for Rapid eXploration of Sequence space (SPARXS), that allows the study of molecular structure, kinetics and interactions for thousands of different sequences simultaneously at the single-molecule level. We, for the first time, combine single-molecule fluorescence with next-generation Illumina sequencing. As a proof of principle we apply SPARXS to study the sequence-dependent kinetics of the four-way DNA Holliday junction, occurring among others during homologous recombination. Using SPARXS we observe the dynamic behavior of 120,000 Holliday junction molecules covering 3750 distinct core sequences, a result unattainable with previous techniques. Overall, the mechanistic insights obtained using SPARXS will give an entirely new view on the relationship between sequence, structure and function. Show less
A strong correlation exists between abdominal aortopathy and atherosclerosis. In thoracic aortopathy however, the prevalence of atherosclerosis and its role in the etiology of thoracic aortopathy... Show moreA strong correlation exists between abdominal aortopathy and atherosclerosis. In thoracic aortopathy however, the prevalence of atherosclerosis and its role in the etiology of thoracic aortopathy remained unknown. This thesis therefore studied the cardiovascular disease burden within this patient group. These results showed that the prevalence of atherosclerosis (i.e. cardiovascular disease burden), in contrast to abdominal aortopathy, is not increased within the thoracic aortopathy population. Show less
In between 1968 and 1973, the Dutch Atlantic was home to four Black Power organizations: the Black Panthers of Curaçao (1968-1970), Antillean Black Power (1969-1970), the Dutch Black Panther... Show moreIn between 1968 and 1973, the Dutch Atlantic was home to four Black Power organizations: the Black Panthers of Curaçao (1968-1970), Antillean Black Power (1969-1970), the Dutch Black Panther Solidarity Committee (1969-1970), and Black Power Suriname / Afro-Sranan (1970-1973). This dissertation asks why and how these organizations aligned with the transnational movement. Based on archival research conducted in Curaçao, Suriname, the United States, and the Netherlands, it argues that they did so because Black Power offered them an alternative path to decolonization. Instead of striving for equal participation in the Kingdom of the Netherlands, as colonial reformists did, or promoting self-reliance, as nationalists did, Black Power activists believed the best way to free themselves from the legacies and realities of colonialism was to join the movement's global network of Black solidarity, cooperation, and unity. Show less
Online behavioral advertising (OBA) is a form of advertising that relies on data about users’ behavior (e.g., clicks, likes, voice commands) and uses artificial intelligence (AI) to place ads that... Show moreOnline behavioral advertising (OBA) is a form of advertising that relies on data about users’ behavior (e.g., clicks, likes, voice commands) and uses artificial intelligence (AI) to place ads that users may be interested in. Ads that AI chooses to display often leave users in awe and concern them about the potential of total surveillance. People using these services have (legitimate) expectations that tech companies or democratic institutions protect their interests. Indeed, the European Union (EU) heavily regulates OBA, requiring, for example, that companies have users’ consent before their surveillance. Yet, these ads monetize most “free” online services and turn companies like Alphabet and Meta into the world’s wealthiest. Therefore, the industry is incentivized to acquire consumers’ consent by any means necessary, often through manipulation. As almost everyone has encountered manipulative “cookie banners” online, many have started to doubt if EU law can effectively protect consumers from the growing power of the tech industry. This thesis builds a framework of manipulation, describes consumer manipulation via OBA, constructs a theory of the harms of this phenomenon, and analyses its boundaries in the EU legal framework. The thesis concludes that the EU framework can effectively safeguard consumers, anticipating that the enforcement of the Digital Services Act (DSA) and the Digital Markets Act (DMA) will put an end to consumer manipulation (and exploitation) via OBA. Show less
This thesis explores North Korea’s influential role in the liberation of Southern Africa. Specifically, it examines the question of how political elites in Southern Africa benefitted from North... Show moreThis thesis explores North Korea’s influential role in the liberation of Southern Africa. Specifically, it examines the question of how political elites in Southern Africa benefitted from North Korean support, from 1960 until 2020. The main argument of this book is that liberation (and not the Cold War) is the leitmotif for African–North Korean relations, as the transition from anticolonial struggles to postcolonial politics is characterised by continuity not change. This approach is based on three assumptions. First, political culture in Southern Africa transcends national boundaries, which is a legacy of the exile dimension of the struggle for liberation. Second, scholarship must shift its lens from states to regimes. Third, the standard periodisation of African history and the Cold War distorts a proper understanding of African–North Korean interactions. Show less
Inaugural Lecture by Prof.dr. Florian A. Schneider on the acceptance of his position as professor Modern China at Leiden University on Monday 6 May 2024
Inaugural Lecture by Prof.dr. Nadine N.W. Akkerman on the acceptance of her position as professor of Early Modern Literature & Culture at Leiden University on Friday 3 May 2024
Oratie uitgesproken door Prof.dr. Nadine N.W. Akkerman bij de aanvaarding van het ambt van hoogleraar Vroegmoderne Literatuur en Cultuur aan de Universiteit Leiden op vrijdag 3 mei 2024