AI-powered emotion recognition, typing with thoughts or eavesdropping virtual assistants: three non-fictional examples illustrate how AI may impact society. AI-related products and services... Show moreAI-powered emotion recognition, typing with thoughts or eavesdropping virtual assistants: three non-fictional examples illustrate how AI may impact society. AI-related products and services increasingly find their way into daily life. Are the EU's fundamental rights to privacy and data protection equipped to protect individuals effectively? In addressing this question, the dissertation concludes that no new legal framework is needed. Instead, adjustments are required. First, the extent of adjustments depends on the AI discipline. There is nothing like 'the AI'. AI covers various concepts, including the disciplines machine learning, natural language processing, computer vision, affective computing and automated reasoning. Second, the extent of adjustments depends on the type of legal problem: legal provisions are violated (type 1), cannot be enforced (type 2) or are not fit for purpose (type 3). Type 2 and 3 problems require either adjustments of current provisions or new judicial interpretations. Two instruments might be helpful for more effective legislation: rebuttable presumptions and reversal of proof. In some cases, the solution is technical, not legal. Research in AI should solve reasoning deficiencies in AI systems and their lack of common sense. Show less
Interest groups play an important role within a democratic society. Less is known about their role within the legal system. Meanwhile, interest groups are the driving force behind many high-profile... Show moreInterest groups play an important role within a democratic society. Less is known about their role within the legal system. Meanwhile, interest groups are the driving force behind many high-profile lawsuits against the Dutch government, such as the lawsuits concerning climate change, the quality of asylum facilities, and the Dutch nitrogen policy. This research focuses on the access of interest groups to the courts. How extensive is their access? Does it threaten or protect a democratic society under the rule of law? The access of interest groups to Dutch administrative and civil courts is evaluated in terms of legitimacy and effectiveness. Since interest group litigation is at the intersection of politics and law, the research adopts an interdisciplinary approach. Beyond the boundaries of Dutch legal scholarship, it seeks insights from social sciences regarding the role of interest groups within the political decision-making process. Additionally, it examines, from a legal sociological perspective, the role that interest groups play in public interest litigation in the United States. As a result, the research explores approaches, concepts, and arguments that have largely remained outside of the Dutch legal legal discourse. Ultimately, this leads to a reassessment of both the legitimacy and effectiveness of interest groups' access to the courts. Show less
A complex community of microbes develops in the infant gut shortly after birth. We call this community the infant gut microbiota. The microbiota influences the health of the infant, which makes the... Show moreA complex community of microbes develops in the infant gut shortly after birth. We call this community the infant gut microbiota. The microbiota influences the health of the infant, which makes the composition and function of the infant gut microbiota an important topic to study. It’s not possible to directly study the development of the microbiota inside the infant, so we are limited to information from fecal samples and laboratory experiments. Because it is so difficult to study, the processes and mechanisms that shape the microbiota also remain unclear. Mathematical models can generate hypotheses and predictions about the unseen inner workings of a system such as the infant gut microbiota.In this thesis we develop a mathematical model that makes predictions both on how bacteria are influenced by the environment and on how they influence the environment. By applying this influence to the environment and repeating the technique, the model can make predictions for how the whole system changes over time. We use this model to make predictions on how changes to the environment, such as the presence of oxygen, antibiotic disturbances, or in particular the presence of oligosaccharides, influence the infant gut microbiota, their metabolism, and ultimately the infant. Show less
In this thesis we push the boundaries of high-resolution imaging at radio frequencies between 100 and 200 MHz. Using the International LOFAR Telescope that spans across Europe we achieve sub... Show moreIn this thesis we push the boundaries of high-resolution imaging at radio frequencies between 100 and 200 MHz. Using the International LOFAR Telescope that spans across Europe we achieve sub-arcsecond angular resolution. We demonstrate mapping of the full field of view of the telescope at its native resolution and use the resulting images to study active galactic nuclei in the Lockman Hole field. Show less
This thesis describes a set of excitability measurements -transcranial magnetic stimulation (TMS) combined with electromyography (EMG) and electroencephalography (EEG), nerve excitability threshold... Show moreThis thesis describes a set of excitability measurements -transcranial magnetic stimulation (TMS) combined with electromyography (EMG) and electroencephalography (EEG), nerve excitability threshold tracking (NETT), and muscle velocity recovery cycles (MVRC)- and the applicability of these tools in early phase clinical drug development. We validated the biomarkers in healthy subjects with registered drugs and showed that the measurements are all repeatable and sensitive to pharmacological effects, even in a small number of subjects. Furthermore, we have evaluated effects of a novel AMPA-positive allosteric modulator with TMS-EMG/EEG, and a first-in-class skeletal muscle-specific chloride channel (ClC-1) inhibitor with MVRC, and the findings helped us to confirm proof-of-mechanism of these compounds in healthy subjects. In conclusion, these measurements proved to be valuable pharmacodynamic biomarkers in two drug development programs, encouraging their further use in clinical development of other future drug candidates targeting cortical-, neuronal-, and muscle cell excitability. The use of such clinical pharmacodynamic biomarkers could improve the quality and efficiency of the development process of drugs for e.g. amyotrophic lateral sclerosis, chronic pain, depression, treatment-resistant epilepsy, and neuromuscular diseases. Show less
This work explores the notion of independence as it relates to international civil servants and secretariats. It identifies the fundamental characteristics of the term and examines how the... Show moreThis work explores the notion of independence as it relates to international civil servants and secretariats. It identifies the fundamental characteristics of the term and examines how the independence of international civil service can erode. It describes the acts and omissions of three main actors responsible for preserving this independence: member states, international organizations, and international civil servants. The work concludes by providing concrete recommendations for strengthening the independence of the international civil service. Show less
The healthcare landscape is constantly evolving. eHealth (electronic health) presents opportunities to alleviate pressure in healthcare, for example by empowering patients to take more control over... Show moreThe healthcare landscape is constantly evolving. eHealth (electronic health) presents opportunities to alleviate pressure in healthcare, for example by empowering patients to take more control over their care. This thesis has examined various digital applications that have already been (partially) implemented. The research primarily focuses on the user-friendliness and effectiveness of these digital applications, aiming to promote self-management and accessibility of healthcare. The digital applications in this thesis relate to requesting diagnostic tests, both with and without involvement of healthcare professionals. Diagnostic tests enable the detection of conditions, such as sexually transmitted diseases for instance. Additionally, research has been conducted on the effectiveness of a self-management program for asthma and COPD. The results generally indicate that patients and citizens, particularly the younger generation, are receptive to online applications aimed at supporting their self-management of health and illness. Nevertheless, certain factors influence their acceptance, such as reliability and user-friendliness. Therefore, it is essential to promote collaboration among all stakeholders to enhance usability and ensure that online applications effectively meet their intended purpose and objectives. Show less
This thesis adopts a data-driven, multimodal approach to explore the complexity of psychiatric disorders, emphasizing the integration of diverse datasets to achieve a deeper understanding of these... Show moreThis thesis adopts a data-driven, multimodal approach to explore the complexity of psychiatric disorders, emphasizing the integration of diverse datasets to achieve a deeper understanding of these conditions. It illustrates this methodology across several chapters, each focusing on different aspects and biomarkers relevant to stress-related psychiatric disorders. Chapter 2 reevaluates the effects of intranasal oxytocin through a multimodal lens. Chapter 3 connects cortisol's in-vivo effects with brain responses and molecular architectures. Chapter 4 introduces a multimodal machine learning model to predict remission in depressive disorder, aiming for both accuracy and explanatory power. Chapter 5 examines the concept of resilience as a discrepancy between expected and observed mental health post-stress, assessing its predictive value for mental health outcomes. Finally, Chapter 6 explores a novel genetic risk score for stress-related disorders, testing its utility and applicability in various contexts. Through a comprehensive and data-centric approach, the thesis aims to uncover new insights into the etiology and treatment of psychiatric disorders, highlighting the importance of considering their multimodal nature. Show less
In the Netherlands, the title of Minister of State is granted to a select set of senior politicians and administrators, generally towards the end of their career. They are appointed by the monarch,... Show moreIn the Netherlands, the title of Minister of State is granted to a select set of senior politicians and administrators, generally towards the end of their career. They are appointed by the monarch, acting on a proposal by the cabinet. In this capacity, they are then asked to perform certain activities or to carry out specific tasks. Both the content of the Minister of State role itself and the appointment process are quite vague. Nevertheless, this exclusive ministerial title has considerable social status. The aim of this research study is to provide insight into the title of Minister of State. The problem description is as follows: What development has taken place in the role of Minister of State; what has the legal and political significance of the Minister of State been; and what can be said about the present-day role of Minister of State, in the Netherlands and in various other countries? Chapter 2 investigates the development of the Minister of State from a historical perspective. In Chapter 3 the various appointments as Minister of State are studied for each monarch. Chapter 4 examines the present-day role of Minister of State. In Chapter 5 a comparative legal study is made of whether other countries also have a Minister of State and what parallels and differences can be seen in relation to this title in the Netherlands.Chapter 6 brings together the findings of the research study and presents the conclusions that were drawn. Show less
In this thesis I highlight the applications of Oxford Nanopore Technologies (ONT) sequencing. This technique is a relatively new approach in the sequencing field, where nanopores are embedded in a... Show moreIn this thesis I highlight the applications of Oxford Nanopore Technologies (ONT) sequencing. This technique is a relatively new approach in the sequencing field, where nanopores are embedded in a membrane, DNA molecules are pulled through nanopores and an electrical current serving as the sequencing signal. This technique yields reads-lengths of >10Kbp and has no theoretical upper limit towards read-length. The positive impact on data quality due to improved chemistry is underlined, improved chemistry leads to less sequencing errors and a more homogeneous coverage over complex genomic architectures. Benefits for increased read-lengths are assessed for resolving fragmented genome assemblies that were previously based solely on short-read sequencing data. Furthermore, the assembly of a large genome using ONT data is described, indicating ONT is a suitable candidate for resolving extremely large genomes using sophisticated assembly approaches. And finally, the potential for on-site sequencing is evaluated. Exploiting simplicity, mobility and accuracy provided by this new technique. The central hypothesis of this thesis is that Oxford Nanopore Technologies long-read sequencing can be valuable for established genomics applications, such as whole genome sequencing and metagenomic characterization of microbial communities. Show less
In the light of the fragility of current liberal democracies, this dissertation aims to contribute to rethinking political order by reconstructing Hegel’s account in the Philosophy of Right. His... Show moreIn the light of the fragility of current liberal democracies, this dissertation aims to contribute to rethinking political order by reconstructing Hegel’s account in the Philosophy of Right. His theory of political order has relevance as it explores how modern freedom, i.e. liberal rights and a market, can coexist with republican self-government. The reconstruction shows how a liberal order, i.e. based on the principle of individual autonomy and an instrumental account of government, must entail a loss of freedom and social and political pathologies: citizens for instance cannot acquire stable identities in the social whole and alienate themselves from the political realm. Moreover, it works out Hegel’s alternative account of political order in which freedom depends on the interplay of the opposed dynamics of the state and society: the state institutions pursuing the good of the community as a whole, while the members of civil society pursue their own good. Finally, the dissertation shows how Hegel offers a coherent and subtle account of republican citizenship and self-government, in which self-government does not depend primarily on the influence citizens exercise on political outcomes but on their ability to identify with the good of the community as a whole. Show less
This dissertation explores the United Nations' comprehensive approach to managing the Israel-Arab Conflict from 1967 to 1982, presenting a shift from examining peace operations as isolated efforts... Show moreThis dissertation explores the United Nations' comprehensive approach to managing the Israel-Arab Conflict from 1967 to 1982, presenting a shift from examining peace operations as isolated efforts to viewing them as interconnected elements of a broader peace architecture. It introduces a critical analysis of the roles played by the Office of Special Political Affairs and the Office of Chief Coordinator of Peacekeeping in the Middle East, arguing that these entities were pivotal in forming a cohesive strategy despite the static mandates of individual peace missions. The research spans six chapters, starting with a historical overview of the UN’s peacekeeping framework since 1948, setting the groundwork for understanding the conflict and the evolution of peacekeeping entities. It then delves into Inter-Operation Collaboration (IOC) and the Secretariat’s political maneuvering, highlighting the impact of significant events like the Camp David Accords and the 1982 Israeli invasion of Lebanon. These events marked a shift in focus from state-centric to Israeli-Palestinian issues, challenging the UN’s influence. The conclusion assesses the UN’s role in shaping the diplomatic and security landscape of the region, underlining the organization's contributions and limitations in fostering peace and stability amidst a complex geopolitical scenario. This research offers valuable insights into the dynamics of UN peacekeeping operations in regional conflicts. Show less
Thromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it... Show moreThromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it at the same time increases risk of bleeding. With nationwide data from Statistics Netherlands, antithrombotic therapy and relevant clinical outcomes were comprehensively examined in the patient population of atrial fibrillation, overall or among those with comorbid cancer. The results suggest the patient population was increasingly receiving anticoagulants, driven by the newly introduced medication- direct oral anticoagulant and guided by the CHA2DS2-VASc score, and meanwhile the patient population experienced fewer ischemic stroke and major bleeding. In spite of these promising changes, suboptimal medication adherence and potential underuse of anticoagulants remain directions for further improvement. Antithrombotic agent use during pregnancy was also examined in the general Dutch pregnant population, which featured a surge in antiplatelet prescriptions, and risk of preeclampsia/eclampsia decreased and several newborn outcomes improved simultaneously. Together, the studies presented in this thesis provide an overview of antithrombotic therapy in the Netherlands in recent years, providing insights for further improving this treatment and relevant patient outcomes. Show less
This dissertation explores the ways in which affective responses to disabled bodies are represented and how this invites us to read these bodies aesthetically. I argue that this affective impact... Show moreThis dissertation explores the ways in which affective responses to disabled bodies are represented and how this invites us to read these bodies aesthetically. I argue that this affective impact can be understood as an affordance, a term I use to describe how the appearance of and interaction with disabled bodies produces affective responses such as fear, wonder, or disgust. I study the relationship between representation and affective reactions through literature and other art forms. Through close readings of literary texts and works of art, this dissertation offers an alternative to so-called model thinking—an approach that emphasizes categorization. Instead, I propose a reading that focuses on how bodily capacities are culturally and socially translated into (dis)abilities. Unlike taxonomic approaches that categorize and generalize, this method allows moving from the particular to the private. Works of art, although prone to generalization, emphasize their unicity and resist categorization. By analyzing how different art forms represent disabled bodies, the dissertation brings a new dimension to understanding our emotional responses and the aesthetic appreciation of bodily diversity. Show less
Drug candidates with a covalent binding mode have gained interest since the approval of multiple covalent anticancer drugs, but were long avoided due to concerns regarding promiscuous reactivity... Show moreDrug candidates with a covalent binding mode have gained interest since the approval of multiple covalent anticancer drugs, but were long avoided due to concerns regarding promiscuous reactivity with off-target proteins. In this dissertation, the scope and versatility of the newly discovered in situ thiol–alkyne reaction is evaluated: the nonactivated alkynes exhibit an unprecedented target reactivity with excellent thiol selectivity, thus potentially outperforming currently used cysteine-reactive warheads. Chapter 1 starts with the history of (ir)reversible covalent inhibition, the reactivity of (non)activated alkynes, and the serendipitous discovery of the thiol–alkyne reaction. Established technologies for direct detection of covalent protein–drug adducts are reviewed in Chapter 2, and in Chapter 3 a detailed guide for the evaluation of (ir)reversible covalent inhibitors to obtain relevant kinetic parameters is provided, accompanied by kinetic simulations and step-wise protocols for enzymatic activity assays. In Chapter 4, the nitrile warhead in reversible CatK inhibitor odanacatib (ODN) is replaced with alkyne warheads to investigate whether it an irreversible covalent adduct is formed with cysteine protease cathepsin K (CatK) despite having a small recognition element. In Chapter 5, we evaluate if nonactivated alkynes can target noncatalytic cysteine residues by replacing the irreversible covalent acrylamide warhead in EGFR/HER2 inhibitor neratinib by an alkyne warhead. In Chapter 6, the impact of substituents on the alkyne warhead is explored using a panel of ubiquitin-based ABPs bearing substituents on the propargylamide warhead. Finally, the most important findings are summarized in Chapter 7, and placed in the context of covalent drug discovery. Show less
In this PhD study, I aim to deepen our understanding of the influence of major mycorrhizal types, namely arbuscular mycorrhizae (AM) and ectomycorrhizae (EM), on the global soil carbon cycle and... Show moreIn this PhD study, I aim to deepen our understanding of the influence of major mycorrhizal types, namely arbuscular mycorrhizae (AM) and ectomycorrhizae (EM), on the global soil carbon cycle and their potential distribution changes under future environmental shifts. The investigation comprises two main perspectives: Firstly, Chapter 2 delves into their direct impact on fungal biomass input to the soil via lab experiments. Secondly, Chapters 3, 4, and 5 explore their role in mediating litter decomposition through modeling. This thesis sheds light on the significance of mycorrhizal fungi in the soil carbon cycle and underscores the necessity of accounting for their effects when analyzing global soil carbon dynamics. Additionally, the research underscores the importance of understanding mycorrhizal fungi responses to environmental changes, given their sensitivity to factors like temperature and precipitation. Show less
Schistosomiasis is a parasitic infection caused by worms of the genus Schistosoma. It is a neglected tropical disease, affecting mainly populations living in poverty without adequate sanitation.... Show moreSchistosomiasis is a parasitic infection caused by worms of the genus Schistosoma. It is a neglected tropical disease, affecting mainly populations living in poverty without adequate sanitation. Treatment relies on one drug mainly, praziquantel, and its efficacy is dependent on the diagnostic tool used.Due to the parasite’s intravascular localisation, it is difficult to directly quantify them in infected humans. Thus, methods of detection like worm-derived circulating cathodic antigen (CCA) in urine or circulating anodic antigen (CAA) in urine and serum, have gained more attention. This thesis aims to explore and shed light on how to interpret schistosome-related circulating antigens CCA and CAA. We have addressed the interpretation of schistosome related assays in endemic and non-endemic regions, supported by data obtained from an animal study. Different diagnostic value can be attributed to different assays within different contexts. The results highlight the importance of a better understanding of antigen excretion patterns by different species to support optimalisation of antigen-based diagnostics of schistosomiasis. Show less
Voltammetry plays a crucial role in modern scientific research by offering valuable insights into the electrochemical properties of materials, with wide-ranging applications in fields such as... Show moreVoltammetry plays a crucial role in modern scientific research by offering valuable insights into the electrochemical properties of materials, with wide-ranging applications in fields such as materials science, energy storage, corrosion studies, and sensor development.Gold, known for its exceptional inertness, provides a unique platform for studying intricate electrochemical processes due to its stability and slow electrochemical behavior. However, certain questions regarding gold voltammetry have remained unresolved throughout history. To address these gaps, our research employed a combination of electrochemical cyclic voltammetry and advanced in situ techniques like surface-enhanced Raman spectroscopy (SERS), Rotating ring-disk electrode (RRDE), and Electrochemical quartz crystal microbalance (EQCM).Through our investigations, we not only redefined the mechanism of gold oxide formation but also uncovered the reasons behind the structural reconstruction of gold oxide. Additionally, we elucidated the electrochemical interfacial structure on gold from a novel perspective focusing on charge distribution.The significance of these findings lies in their fundamental nature, with the potential to inspire researcher to reconsider interpretations of voltammetry behaviors across various materials and research fields. We anticipate that our work will stimulate further exploration and innovation in the realm of electrochemistry, paving the way for new discoveries and advancements. Show less
Despite the history of studies on methanol formation from CO2, the dominant elementary reaction steps that constitute the chemical mechanism for this catalyzed process are not determined. Two main... Show moreDespite the history of studies on methanol formation from CO2, the dominant elementary reaction steps that constitute the chemical mechanism for this catalyzed process are not determined. Two main issues may cause doubt about the current level of understanding: 1) the very large difference in the coverage-dependent sticking probabilities for CO2 and CO and unavoidable CO contamination 2) the complex oxidation of the copper surface and unavoidable build-up of a (partial) oxide layer.In this thesis, we studied the sticking probability of O2 on Cu(111) and compared results to previous experimental and theoretical results. The dissociative chemisorption of O2 on Cu(111) is a direct, activated process with a minimum barrier of approximately 100 meV.In an attempt to develop a method that may undeniably quantify the reactivity of CO2 onto clean and H-containing Cu surfaces, we investigated co-adsorbed CO and O on Cu(111) and Cu(211) with RAIRS. Cu(211) oxidizes much more readily than Cu(111). For incomplete oxidation, the system CO adsorbs to small isolated metallic Cu edges and patches. Fully oxidized Cu(211) binds CO but in a rather different form than clean metallic Cu. The vibrational frequency of adsorbed CO is changed as the co-adsorbed O coverage varies on Cu(211). Show less
Contrary to common belief, sign languages are distinct across different communities and cultures, evolving organically through interactions among deaf people, rather than being based on spoken... Show moreContrary to common belief, sign languages are distinct across different communities and cultures, evolving organically through interactions among deaf people, rather than being based on spoken languages. Each sign language has its own grammar, vocabulary, and cultural nuances, with variations even within a single country, showcasing the diverse communication methods within the deaf community. Deaf individuals often face encouragement to use spoken language techniques like lipreading or text communication, highlighting a bias towards spoken languages. This is compounded by the lack of sign languages in linguistic technologies, emphasizing the need for more inclusive research and development. This dissertation aims to address this gap using machine and deep learning to improve sign language processing and recognition. It covers six chapters, introducing methods for video-based sign annotation, webcam-based sign language dictionary search, and ranking systems for sign suggestions. It also explores tools for visualizing and comparing sign language variation, contributing valuable resources to linguistic research. Show less