International Migration, Integration and Social Cohesion online publications
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Rethinking freedom from the perspective of refugees:Lived experiences of (un)freedom in Europe’s border zones
Full text linkIn mainstream political discourse, refugeehood is increasingly being associated with victimhood, powerlessness, and abnormality, and political crises. On the one hand, refugees are, often, viewed as voiceless victims who should be offered protection and assistance on humanitarian grounds under exceptional circumstances. On the other hand, they are, increasingly, being portrayed as enemy-like strangers who pose a threat to the borders, stability of receiving states, and the well-being of their citizens. This prevailing framework fundamentally disregards refugees’ political subjectivity and ignores emancipatory phenomena and practices of freedom, which are embedded and expressed in refugees’ migratory movements.This philosophical investigation aims to contribute to our understanding of the dynamic relationship of freedom and unfreedom from the perspective of refugees. To examine this dynamic relationship, this study situates itself in the autonomy of migration approach and draws on narratives and lived experiences of refugees, which were collected during in-depth interviews with refugees (Greece). These experiential accounts have been analysed and theoretically discussed in accordance with the guidelines of Interpretative Phenomenological Analysis (IPA). Through an interpretative process, this study critically contextualizes refugees’ perceptions and understandings of freedom in ongoing theoretical discussions concerning refugeehood and freedom. Based on these critical discussions, this study develops a theoretical examination of the dynamics of freedom and unfreedom in different spatio-temporal phases of refugeehood. In doing so, it explores the multifaceted act of flight, lived experiences of (un)freedom, socio-political structures of abandonment, and autonomous relations and arrangements by which refugees enact freedom in receiving states. Moreover, it challenges the prevalent conceptual distinctions between citizens versus non-citizens, hosts (nationals) versus guests (migrants), genuine refugees versus economic migrants, and the included (right-holders) versus the excluded (the rightless)
Rethinking freedom from the perspective of refugees:Lived experiences of (un)freedom in Europe’s border zones
Full text linkIn mainstream political discourse, refugeehood is increasingly being associated with victimhood, powerlessness, and abnormality, and political crises. On the one hand, refugees are, often, viewed as voiceless victims who should be offered protection and assistance on humanitarian grounds under exceptional circumstances. On the other hand, they are, increasingly, being portrayed as enemy-like strangers who pose a threat to the borders, stability of receiving states, and the well-being of their citizens. This prevailing framework fundamentally disregards refugees’ political subjectivity and ignores emancipatory phenomena and practices of freedom, which are embedded and expressed in refugees’ migratory movements.This philosophical investigation aims to contribute to our understanding of the dynamic relationship of freedom and unfreedom from the perspective of refugees. To examine this dynamic relationship, this study situates itself in the autonomy of migration approach and draws on narratives and lived experiences of refugees, which were collected during in-depth interviews with refugees (Greece). These experiential accounts have been analysed and theoretically discussed in accordance with the guidelines of Interpretative Phenomenological Analysis (IPA). Through an interpretative process, this study critically contextualizes refugees’ perceptions and understandings of freedom in ongoing theoretical discussions concerning refugeehood and freedom. Based on these critical discussions, this study develops a theoretical examination of the dynamics of freedom and unfreedom in different spatio-temporal phases of refugeehood. In doing so, it explores the multifaceted act of flight, lived experiences of (un)freedom, socio-political structures of abandonment, and autonomous relations and arrangements by which refugees enact freedom in receiving states. Moreover, it challenges the prevalent conceptual distinctions between citizens versus non-citizens, hosts (nationals) versus guests (migrants), genuine refugees versus economic migrants, and the included (right-holders) versus the excluded (the rightless)
A diluvial land:Earth histories in the early modern Low Countries, 1550-1830
Full text linkIn the seventeenth and eighteenth centuries, scholars and naturalists reimagined the history of the earth—crafting new chronologies, amassing new evidence, and resituating humans within the history of nature. This dissertation looks to the early modern Low Countries to argue that new ideas about Earth’s past drew on two principal sources: the material evidence of the landscape and the textual evidence of the Bible and other ancient cosmologies. Before 1600, commentators in Flanders and Holland looked to the Rhine delta and the North Sea to explain the formation of these lowlands. By the mid-seventeenth century however, the coastal plain was increasingly envisioned as a diluvial land, shaped by Noah’s flood and other deluges. By the late eighteenth century, the story had changed again, as fossils became the key markers of epochs in earth history. In six chapters, this dissertation charts the rise and gradual decline of the biblical narrative between 1600 and 1800. It explores the interplay between scholarly debate and local conceptions of the landscape, delving into hydrological, antiquarian, and natural historical discourses about the geography of the Northern and the Southern Netherlands.This dissertation ties transnational debates about biblical interpretation and natural philosophy to more local histories, situated in the particular environments of the Low Countries. It thus shows how even the most global of all learned debates—about the formation of the earth—was rooted in local circumstances
Metaphor use in aphasia
Full text linkIn the conceptual metaphor theory (CMT), one tenant is that metaphors are ubiquitous in our everyday language. This dissertation tried to make a thorough investigation into how linguistic metaphors are used by people with aphasia (PWA). Aphasia is an acquired language disorder that affects people’s language production and understanding; it can be divided into two types: non-fluent and fluent, according to the fluency of sufferers’ speech. Some former studies have revealed deficiencies of certain word classes produced by these two groups of PWA. Apart from linguistic metaphors, the metaphor use in aphasia can be also discussed under the scope of CMT: in people’s speech about aphasia, aphasia treatment, and rehabilitation, we can find conceptual metaphors and analyse them to see how aphasia is conceptualized in discourse. The overall research goal of this dissertation is to examine how metaphors are used in aphasia from two perspectives: linguistic and conceptual.Results have shown features of PWA’s production of linguistic metaphors in some word classes; in some word classes, metaphor distribution is not balanced in different types of aphasia. By analysing the interaction between metaphor, word class, and participant group in English and Mandarin data, we can have a deeper understanding of metaphor use by PWA. As for the analysis of metaphorical framings about aphasia and aphasia recovery, it can be helpful for practitioners and family caregivers to communicate with PWA in the rehabilitation process. Moreover, metaphorical framings on aphasia can shape how we think about aphasia and PWA
Molecular regulation of neural stem cell quiescence by FoxO transcription factors
Full text linkNeural stem cells (NSCs) are the origin of new neurons in the adult brain. The majority of NSCs reside in a state outside of the cell cycle known as quiescence, which helps to limit exhaustion of the NSC population. During aging, however, NSCs decline in number and grow increasingly quiescent, which both impair adult neurogenesis. Only finely tuned regulation of their cell cycle can ensure lifelong neurogenesis. We discovered that transcription factor FoxO6 is a novel regulator of NSC fates. In contrast to FoxO3, FoxO6 suppresses NSC quiescence during aging.Interestingly, NSCs lacking FoxO6 exhibit a glioma-like molecular signature whereas FoxO6 expression is a prognostic factor for glioma patients. This indicates a role for FoxO6 in the oncogenic transformation of neural stem cells towards brain cancer stem cells. In addition, these FoxO6-deficient NSCs show strongly reduced expression of Hmgn2, an epigenetic regulator of the NSC lineage and which we identified to be a transcriptional target of FoxO3. An emerging role of NSC regulation is the circadian control over their cell cycle entry. We found that FoxO3 controls the cellular circadian clock in NSCs and is necessary for the correct timing of their proliferation in the hippocampus. Together, this shows that an interplay between FoxO3 and FoxO6 regulates NSC quiescence and is required for healthy aging
Potassium and its effect on natriuresis and cardiovascular outcomes in health and kidney disease
Full text linkIn this thesis, we explored the complex relationship between potassium intake, natriuresis, blood pressure (BP), and cardiovascular disease (CVD) outcomes in health and chronic kidney disease (CKD). In the first chapter, we studied dietary potassium intake in the general population and found that higher intake was associated with lower systolic BP and reduced CVD risk—particularly in women. Notably, in women, the association between potassium intake and systolic BP was modified by sodium intake. In the following chapters we examined the acute effects of a single oral potassium load on potassium and sodium balance. In healthy individuals, both changes in acid–base balance and aldosterone levels contributed to potassium uptake and excretion. Moreover, in healthy individuals, natriuresis increased in response to a single oral load of potassium, while in patients with CKD G3b–4 potassium-induced natriuresis was absent. Next, we evaluated the effects of 14-d supplementation of potassium chloride in patients with CKD G3b–4. We showed that potassium supplementation increased plasma potassium, but had no significant effect on BP or eGFR. Also, in proteinuric CKD patients, the proteinuria, but not BP-lowering response to losartan during a habitual high-sodium diet was hampered during high potassium intake. However, differences disappeared after sodium status change by low-sodium diet. Finally, we reviewed potassium management in haemodialysis patients, emphasizing the need for individualized strategies. Altogether, this thesis highlights that the beneficial effects of potassium may highly depend on patient characteristics including sex, sodium intake, kidney function and use of single renin-angiotensin-system (RAS) blockers
Lending colour to the black box:Insights into the course and burden of primary sclerosing cholangitis
Full text linkPrimary sclerosing cholangitis (PSC) is a rare cholestatic liver disease marked by multifocal bile duct strictures and is strongly associated with inflammatory bowel disease (IBD). The disease runs an unpredictable course with increased risk of developing colorectal and hepatobiliary cancers, frequently culminating in liver transplantation. While its cause remains unclear, no proven medical therapy exists to halt disease progression.Part I assessed the disease burden of PSC. Although individually rare, cholestatic liver diseases pose a significant epidemiological and economical burden. Dutch registry data revealed that patients lose an average of 11.8 healthy life-years in the first 30 years post-diagnosis, spend 12 hospital days annually, incur average yearly medical costs of €12,169, and experience a 25% work productivity loss. Health-related quality of life is reduced, particularly by IBD symptoms, pruritus, and advanced liver disease, but improves post-transplant.Part II explored the gut–liver axis. Proctocolectomy with permanent ileostomy was linked to a 60% reduced risk of transplantation or PSC-related death, while colectomy with remnant colon or pouch did not show survival benefit. IBD presence or endoscopic activity showed no direct impact on transplant-free survival, presumably due to persistent microscopic gut inflammation.Part III evaluated biliary tract interventions. Cholecystectomy showed no significant survival effect and should therefore not be avoided in PSC. Ursodeoxycholic acid (UDCA) use did not improve long-term outcomes, though a possible chemoprotective effect against hepatobiliary malignancy was noted, warranting further study
Development of a bacterial chassis for amine synthesis
No full textThe biocatalytic synthesis of chiral amines from carbonyl compounds and ammonia represents a major advancement in sustainable synthetic chemistry. Using whole cells for bioamination offers advantages such as low preparation cost and direct applicability; however, amine toxicity often limits these reactions when living cells are used. This thesis focuses on the generation, characterization, and biocatalytic application of amine-tolerant bacteria for sustainable, high-yielding amine synthesis. We employed adaptive laboratory evolution to generate amine-tolerant Escherichia coli strains that enabled the enantioselective reductive amination of prochiral ketones, achieving yields of up to 80% at high substrate loadings (up to 23 g L-1), without cofactor supplementation. Additionally, the adapted strains facilitated the bioamination of alcohols with modest to good efficiency—typically outperforming non-adapted cells—and enabled the bioproduction of short-chain alkyl amines via enzymatic decarboxylation of amino acid precursors. The genomes of the amine-tolerant strains revealed a multifactorial adaptive response—primarily involving membrane modifications, stress coping, and regulatory mechanisms—that conferred cross-resistance to structurally diverse amines, likely through cell reinforcement or amine exclusion. Collectively, this thesis deepens our understanding of microbial adaptation to chemical stress and advances the development of robust whole-cell biocatalysts for amine production.</p
Plants for health:Investigating the broader impacts of the Plants for Joints lifestyle intervention
Full text linkThis thesis builds upon the Plants for Joints (PFJ) randomized controlled trials (RCTs), which demonstrated significant improvements in disease activity in rheumatoid arthritis (RA), as well as pain, stiffness, and physical function in osteoarthritis (OA). It extends these findings by investigating secondary effects, underlying mechanisms, perceived usefulness, cost-effectiveness, and long-term outcomes of the PFJ lifestyle intervention.A systematic review showed that high-fiber, plant-based diets are consistently more effective at improving clinical and microbiome outcomes in chronic inflammatory diseases, compared to other dietary patterns. Secondary analyses of the PFJ RCTs showed significant reductions in body fat and liver fat content, improvements in gut barrier integrity, favorable shifts in microbiome composition and metabolites, and positive effects on stress-related parameters in RA. Further research indicated no evidence of mucosal anti-modified protein antibody production in the gut.A process evaluation highlighted high participant satisfaction, empowerment, and the importance of self-monitoring, social support, and guidance. Economic analyses demonstrated that the PFJ intervention was on average less costly and more effective compared to only usual care. Long-term follow-up over two years showed sustained improvements in disease activity, pain, stiffness, physical function, several metabolic risk factors, and reduced medication use, with continued adherence to intervention recommendations.Together, these findings show PFJ is a feasible, acceptable, and sustainable lifestyle intervention with broad health benefits. Beyond symptom relief, PFJ positively influences body composition, metabolic health, the gut microbiome, stress regulation, and quality of life, underscoring its potential as an adjunct treatment for RA, OA, and possibly other chronic diseases
Next-generation bNAbs:Antibody engineering strategies for HIV-1 cure
Full text linkDespite ART effectively suppressing HIV-1 replication, viral reservoirs persist and prevent a cure. Broadly neutralizing antibodies (bNAbs) can neutralize virions and mediate clearance of infected cells, but their efficacy is limited by low Env density, high viral diversity, immune cell exhaustion, and short antibody half-life. To address these challenges, this thesis focused on antibody engineering strategies to enhance bNAb potency, effector function, and capacity to eliminate HIV-1–infected cells. Engineering approaches included developing multivalent constructs to increase Env binding, glycoengineering to boost FcγRIIIa affinity and NK cell activation, and Fc modifications to enhance complement-dependent cytotoxicity. Subclass switching, hinge elongation, and introduction of activating mutations further optimized antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). In addition, bispecific antibodies were designed to simultaneously target HIV-1 Env and NK cell receptors, achieving improved immune cell recruitment and killing of infected cells. Overall, this thesis demonstrates that antibody engineering can overcome key limitations of current bNAb therapies. By improving effector function, immune engagement, and mechanisms of infected cell clearance, engineered antibodies show strong potential to reduce the viral reservoir. These findings support the advancement of next-generation antibody therapies as a promising step toward durable ART-free control or a functional cure for HIV-1