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
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
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
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
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
Security is something that people tend to care about. But is it also something that they should care about? To explore this question, this dissertation first develops a new conceptual framework of... Show moreSecurity is something that people tend to care about. But is it also something that they should care about? To explore this question, this dissertation first develops a new conceptual framework of security. Next, it analyses how security relates to some key values for liberal democratic societies. The first of these is well-being. It is argued that there are important ways in which security can contribute to somebody’s well-being – but there are also ways in which security may hamper a person’s flourishing. The second value is freedom. It is shown that in public decision-making freedom and security may come at each other’s cost – yet there are also ways in which the two can work to each other’s benefit. The third value is equality. It is demonstrated that in order for a society to meet the demands of equality it must provide its members with a particular set of securities – while at the same time the pursuit of equality puts another set of securities out of reach. Ultimately, this dissertation finds no reason for considering security to be good for its own sake, but it argues that security can be good for the sake of well-being, freedom, and equality. Show less
Human vocal communication and music perception represent advanced cognitive skills, seemingly innate and universal. These faculties encompass a range of perceptual and cognitive abilities. Cross... Show moreHuman vocal communication and music perception represent advanced cognitive skills, seemingly innate and universal. These faculties encompass a range of perceptual and cognitive abilities. Cross-species research sheds light on the origins of musicality by investigating whether these traits are shared by nonhuman species. Songbirds, notably zebra finches, serve as valuable models due to their complex vocalizations and similarities to humans in auditory perception. My thesis explored zebra finches' sensitivity to spectral and temporal sound features. Chapter 2 examines the influence of song duration and spectral characteristics on song discrimination, while Chapter 3 tests song preferences. Chapter 4 investigates sequential and spectral feature recognition. Chapter 5 focuses on melody recognition. Zebra finches demonstrate perceptual flexibility, adapting focus based on stimulus characteristics. These findings underscore the importance of training conditions and stimulus nature in shaping auditory perception. Overall, my thesis enhances understanding of auditory cognition and cognitive flexibility among songbirds. Show less
This thesis summarizes a PhD research project, in which we successfully developed and tested a smartphone-based version of the AAT. We used the mobile AAT to show that approach-avoidance tendencies... Show moreThis thesis summarizes a PhD research project, in which we successfully developed and tested a smartphone-based version of the AAT. We used the mobile AAT to show that approach-avoidance tendencies can undergo substantial state-like changes. We further demonstrate how these changes can be systematically related to other state-variables and how important health-related outcomes such as overweight and obesity, can be explained by disruptions of these dynamics. Our findings have broad implications for approach-avoidance research and task-based research in general, as they reveal how smartphones can be used to get insights into the dynamic nature of task outcomes and how (disruptions of) these dynamics can have important real-life consequences. Show less
Thyroid cancer is a rare cancer with an excellent prognosis with standard care (including surgery and radioactive iodine therapy). However, a minority may show progression to refractory status.... Show moreThyroid cancer is a rare cancer with an excellent prognosis with standard care (including surgery and radioactive iodine therapy). However, a minority may show progression to refractory status. These advanced radioactive iodine-refractory thyroid cancer patients often have an aggressive disease course and poor prognosis. Unfortunately, no good treatment options are available for these patients.The registered drugs for this purpose include molecularly targeted therapy with the tyrosine kinase inhibitors (TKIs) lenvatinib, sorafenib, and as second-line cabozantinib. These agents were shown to delay progressive disease in clinical trials, but not overall survival. Moreover, the setting of a clinical trial is often stricter than real-life, as reflected by less favorable outcomes in real-world data. Furthermore, these drugs frequently have (intolerable) adverse events. When the limited treatment options for refractory thyroid cancer have been exhausted, inclusion in clinical trials is often recommended by international guidelines.More recent ‘basket trials’ also study tumor type-agnostic prescription of drugs based on molecular tumor profiling; e.g. an ALK TKI in presence of an ALK gene fusion. The molecular characterization of neoplasms may also improve diagnosis and/or help direct the further management strategy; e.g. in indeterminate thyroid cytopathology, or in specific cases of Multi-UniFocality in contrast to multifocality. Show less
This thesis explores ancient Egyptian descriptions of sicknesses of the inner body, the concepts used to understand them, and the trends in associated therapeutic applications for healing. It... Show moreThis thesis explores ancient Egyptian descriptions of sicknesses of the inner body, the concepts used to understand them, and the trends in associated therapeutic applications for healing. It concludes that the ancient Egyptian system of understanding recorded in writings—while somewhat obscured as the surviving texts were never intended to be descriptive of ideas—can be compared to other ways of thinking and categorising sickness experiences as found in other written cultures. Especially in terms of how such ideas are constructed and how therapies are associated with such concepts. Similarities can be observed in terms of core concepts and associated therapeutic applications recorded in cuneiform compendia of comparable age from Mesopotamia. Rather than using these observations as evidence of an influence of one culture over another, it is argued that these writings include practices and ideas which can instead be considered common to this region of the world, rather than as exclusive and invariably peculiar either the Egyptian and/or Mesopotamian cultures. Show less
Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by limited treatment options and unfavorable clinical outcomes. Therefore, the research described in this thesis... Show moreTriple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by limited treatment options and unfavorable clinical outcomes. Therefore, the research described in this thesis focused on the exploration of novel targeted therapies for TNBC. Through high-throughput screening, we assessed the responsiveness of TNBC cells to kinase inhibitors, which indicated a notable sensitivity to cyclin-dependent kinase (CDK) inhibitors. Building upon these findings, this thesis systematically compares the efficacy of targeting various transcription-associated CDKs, with CDK9 and CDK12 emerging as highly potent targets for disrupting TNBC cell proliferation. Transcription-associated CDKs play multiple roles in regulating mRNA transcription. Yet, inhibitors of these CDK’s induced selective, rather than global, changes in gene expression. This provides insights into their mechanisms of action and suggesting potential opportunities for combination therapy. Furthermore, our research elucidated the mechanism underlying the synergistic effects of combining kinase inhibitors with transcriptional CDK inhibitors, by demonstrating that this is mediated through the inhibition of cellular drug efflux by ABCG2. In conclusion, this thesis highlights the potential of transcription-associated CDK inhibitors as a promising avenue for treating TNBC. The insights from this thesis will help to further steer the (pre)clinical development and strategy of using transcription-associated CDK inhibitors for the treatment of TNBC. Show less
Accurate prediction of the unbound drug concentration-time profile at the CNS target site is crucial for the assessment of the right drug concentration-effect relationship. PBPK models have... Show moreAccurate prediction of the unbound drug concentration-time profile at the CNS target site is crucial for the assessment of the right drug concentration-effect relationship. PBPK models have supported the PK prediction of the CNS target sites and the translation of PK data between species and between populations, given their mechanistic, physiology-based structure. In this thesis, we have developed a CNS PBPK model which could predict adequately the brainECF, brainICF, and CSF unbound PK profiles and provide important insights into the brain unbound pharmacokinetics of patients with CNS diseases. Early prediction of the brain target site pharmacokinetics of the right patient population can prioritize drugs with the favored brain PK profiles, which might optimize and accelerate the CNS drug development process. Show less
This thesis aims at identifying the conducive conditions of coercive diplomacy in the context of nuclear proliferation. Drawing on the US experience with Iran, Libya, and South Africa, we examined... Show moreThis thesis aims at identifying the conducive conditions of coercive diplomacy in the context of nuclear proliferation. Drawing on the US experience with Iran, Libya, and South Africa, we examined the driving factors behind US coercive diplomacy’s divergent and paradoxical results or outcomes in these countries. We chose our case studies based on two factors: the different stages or levels of their nuclear programs when confronted by the US and the nature of the demands formulated by the coercer in relation to the bilateral relations of the parties involved. We hypothesized that two conditions could compel a target subjected to coercive diplomacy to abandon its nuclear (weapons) program: if the coercer’s strategy exploits the target’s vulnerabilities and if the coercer demonstrates the motivation to have a sustained campaign to compel its target to abandon its nuclear weapons program. The interactions between the US and each of the targets mentioned above provide insights into improving coercive diplomacy, both theoretically and practically. The interplay between domestic politics and international pressures theoretically inspires our approach. We emphasized the critical role of domestic actors in alleviating or increasing systemic pressure related to the targets’ nuclear programs. We used neoclassical realism and process tracing to describe these dynamics and unravel the causal relationships between the coercer’s demands and the targets’ responses. Using the structured-focused comparative methodology, we reinforced our findings’ relevance and triangulated our primary and secondary sources. Our findings support the hypothesis of the driving effect of domestic variables in relation to external pressures. Hence, we identified similar and diverse mechanisms in our three cases, which helped us verify the validity of our initial hypotheses and confirmed the relevance of our research strategy regarding the complexity of coercion dynamics in the non-proliferation domain. Show less
Betrokken burgers vormden de ruggengraat van de Republiek. Het dagelijks leven draaide voor een groot deel op buurtorganisaties, gilden en schutterijen – en dat waren juist de stedelijke... Show moreBetrokken burgers vormden de ruggengraat van de Republiek. Het dagelijks leven draaide voor een groot deel op buurtorganisaties, gilden en schutterijen – en dat waren juist de stedelijke instituties waar zij deel van uitmaakten. In 1796 kondigden de Bataafse revolutionairen het einde van sommige van deze instellingen af en introduceerden zij het staatsburgerschap. Maar was daarmee de rol van de stedelijke burger ook uitgespeeld?Dat komen we te weten als we luisteren naar de stadsbewoners zelf. Aan de hand van de levens van Haarlemmers en Groningers tussen 1747 en 1848 illustreert dit boek het voortbestaan van lokaal burgerschap. Zij komen aan het woord via verzoekschriften, kronieken, gelegenheidsgedichten, vergadernotulen en mondelinge klachten op de burgemeesterskamer. Hoe zag de ideale stedelijke gemeenschap er volgens hen uit? Welke rechten en plichten had een burger in hun ogen? En wat waren de dure plichten van een stadsbestuurder? Voor dit burgerschap putten stadsbewoners met souplesse uit traditionele én revolutionaire idealen en praktijken. Show less
This book examines the issuance of mining licenses in Indonesia from an environmental perspective. It shows how mining licensing has directly contributed to environmental degradation and how... Show moreThis book examines the issuance of mining licenses in Indonesia from an environmental perspective. It shows how mining licensing has directly contributed to environmental degradation and how consecutive governments have failed to take effective action addressing this problem. The main cause is the low quality of the relevant laws and policies, which is mostly a result of the priority law- and policymakers accord to mining development and a lack of interest in and knowledge about solving environmental problems. This situation has been exacerbated by a lack of public participation and bureaucratic “siloism”: government agencies often develop their own policies and regulations without efforts at co-ordination with other relevant government agencies. Only in a few cases have there been better results, when government agencies developing a policy had a strong interest in its implementation, when their officials disposed of adequate expertise, and when there was a favourable national political situation. Unfortunately, these conditions have rarely been present in Indonesia. Show less
The application of nanomaterials in industrial processes and consumer products provides many societal benefits, but can also lead to the release of nanomaterials into the environment. The work in... Show moreThe application of nanomaterials in industrial processes and consumer products provides many societal benefits, but can also lead to the release of nanomaterials into the environment. The work in this dissertation aims to provide insights into the potential environmental impacts that may follow from this, with specific reference to populations and communities of freshwater invertebrates. Based on experimental studies conducted under conditions reflecting those in natural ecosystems, this dissertation shows that commonly applied methodological approaches can lead to an underestimation of the long-term impacts of nanomaterials on freshwater organisms, particularly at the level of populations and communities. In doing so, this dissertation provides perspective on the role of relevance and realism in ecotoxicological assessments, and shows that impact assessments at higher ecological levels can provide sensitive and reliable insights that can serve as a basis for regulation, and guide the development of safer and more sustainable chemicals, substances and materials. Show less
Innovation plays an essential role in firms' competitiveness and long-term success. It varies from different types, ranging from run-of-the-mill innovation that brings incremental changes to... Show moreInnovation plays an essential role in firms' competitiveness and long-term success. It varies from different types, ranging from run-of-the-mill innovation that brings incremental changes to existing technologies to radical innovation that breaks from existing trajectories. The aim of this PhD dissertation is to integrate radical innovation and social network literature to broaden theoretical understanding, especially contribute to the literature on social networks, creativity, and innovation, and inform innovation management by unpacking the drivers and effects of radical innovation. Focusing on the long-standing debates in the social network literature regarding which types of networks are more advantageous for innovation, this dissertation starts with investigating how tie strength and structural holes collectively affect innovation radicalness at a location within an innovating firm. Then this dissertation investigates how social structure for producing a creative idea influences the adoption and future use of its innovations and makes a novel contribution by exploring how this effect is contingent on the radical nature of the creative idea. In addition to contributing to this long-standing debate, this dissertation also investigates how radicalness affects the private value for the innovating firm. Show less
This research investigates tensions associated with positive organizational change (POC) that prioritizes strengths-based dialogue over talk about organizational problems or deficits (Fitzgerald et... Show moreThis research investigates tensions associated with positive organizational change (POC) that prioritizes strengths-based dialogue over talk about organizational problems or deficits (Fitzgerald et al., 2010) by bridging the concept of organizational shadow (Bowles, 1991; Fitzgerald et al., 2010; Jung, 1968) with dialectical tension theory (Baxter & Simon, 1993). A recent flurry of studies suggests toxic positivity results in the marginalizing of individuals for expressing their emotions that may not always be positive (Collins, 2022; Cross, 2022; Tufvesson, 2020). A key question this research addresses is what do with the "elephants in the room" that represent what people think is undiscussable in a POC context? Interviews with 41 organizational development practitioners, with more than 600 cumulative years of experience leading POC initiatives using the Appreciative Inquiry (AI) methodology, identified the contexts in which tensions are likely to arise, the theoretical implications of tensions, and practical strategies to navigate tensions in a POC context. This study’s findings advance scholarship on positive organizing by naming the voice, leadership, and temporal shadows. These shadows emerge as three dialectical tensions: free expression and limited expression of what is discussible in the change process, hierarchical and collaborative leadership, and short-term orientation versus long-term orientation. The results of this study demonstrate experienced POC practitioners navigate tensions underlying the voice, leadership, and temporal shadows by using nuanced strategies, such as creating space to hear divergent perspectives, coaching leaders to demonstrate agility in support of collaborative initiatives, and reframing tension such that one pole does not negate the other. Show less
This dissertation showed that physicians must be aware of the constraints that allow them to identify or obviate (un)desirable effects most notably if they evaluate these effects in a blinded... Show moreThis dissertation showed that physicians must be aware of the constraints that allow them to identify or obviate (un)desirable effects most notably if they evaluate these effects in a blinded matter. Unblinding might partially mitigate the limitation, but current measurement methods have gaps that we should remain aware of. Detailed measurements of subintervals with characterization of ion channel profiles, concentration QTc modelling, or machine learning might help physicians in their decision making in the future. Show less
