International Migration, Integration and Social Cohesion online publications
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Apathy as a syndrome:Focus on Parkinson’s disease and deep brain stimulation
Get PDFDit proefschrift onderzoekt de toegenomen prevalentie van apathie bij de ziekte van Parkinson nadat patiënten een behandeling met diepe hersenstimulatie ondergaan. Er zijn meerdere hypotheses voor het ontstaan van apathie na diepe hersenstimulatie, waardoor er verschillende subtypes van apathie worden gevormd die corresponderen met verschillende ontstaansmechanismen. Dit proefschrift bestudeert met name het directe stimulatie effect van diepe hersenstimulatie op apathie, waarbij een MRI studie aanwijzingen ziet voor suboptimale plaatsing van de diepe hersenstimulatie electrode, en hoofdstuk 8 suggereert dat er een subset van patiënten bestaat die profiteren van meer dorsale stimulatie van de nucleus subthalamicus
The human genome and microbiome in cardiometabolic disease:Exploration through sequence-based technologies
Get PDFIn this thesis we used several different sequence-based technologies to explore the role of the human genome and microbiome in cardiometabolic disease. After introducing the cardiometabolic diseases that we investigated, as well as the human genome and microbiome and the methodologies that we applied in Chapter 1, we started off with studies focusing on the relationship between the human genome and cardiometabolic disease in part I. In Chapter 2, we studied the association between several genetic risk scores related to either development of type 1 diabetes, development of type 2 diabetes or C-peptide production and residual beta cell function and glycaemic control in type 1 diabetes patients. In Chapter 3, we identified new intronic variants in the LDLR gene and analysed if they could explain the FH phenotype in yet genetically undiagnosed patients. Thereafter, in part II, we dived into the relationship between the gut microbiome and cardiometabolic disease. In Chapter 4, we reviewed the existing literature on the interaction between medications prescribed for cardiometabolic disease and the gut microbiome. Additionally, we analysed the relationship between the gut microbiome composition and both metabolic syndrome (Chapter 5) and type 2 diabetes (Chapter 6) in a multi-ethnic cohort. Finally, the contribution of the human genome and microbiome were combined in part III, where we explored the role of gut microbial molecular mimicry in the autoimmune response to InsB9-23 of type 1 diabetes patients with a specific HLA-DQ8 genotype
The role of TNNI3K in cardiac disease:Clinical and molecular perspectives
Get PDFTroponin I-interacting kinase (TNNI3K), a protein kinase predominantly expressed in the heart, has been associated with various cardiac pathologies. Yet, the underlying disease mechanisms remain unclear. This thesis explores the role of TNNI3K in cardiac disease from both clinical and molecular perspectives.Our research identified that TNNI3K missense, rather than loss-of-function, variants are significantly associated with dilated cardiomyopathy and arrhythmias. Moreover, we identified two novel TNNI3K variants with reduced kinase activity in families with congenital junctional ectopic tachycardia. These findings also suggest that altered TNNI3K kinase function, rather than protein absence, is a key driver of pathogenicity.To further explore the TNNI3K disease mechanisms, we created mouse models homologous to two pathogenic human TNNI3K variants with enhanced or reduced kinase activity. These models exhibited prolonged PR intervals and early-stage dilated cardiomyopathy. Phosphoproteomic profiling of cardiac tissue revealed tissue-specific alterations in biological processes.Next, we presented PR interval prolongation in mice expressing TNNI3K, which was not observed in mice expressing kinase-dead TNNI3K. This prolongation occurred independently of atrial electrical remodeling or structural remodeling in the atrioventricular node. Additionally, connexin-45 was identified as a novel target, with reducing gap junctional conductance and increasing protein expression in presence of TNNI3K. Further phosphoproteomic studies uncovered additional interactors and mechanisms of action, identifying Hcn4Ser719 as a promising phosphorylation target regulated by TNNI3K.Overall, this thesis provides novel insights into the clinical and molecular mechanisms of TNNI3K in cardiac disease, highlighting its potential as a therapeutic target for cardiac conduction disorders and cardiomyopathies
Categories on the move:Governing refugees in transnational admission programmes to Germany
Get PDFIn light of record numbers of displaced people worldwide, surrounded by a rhetoric of crisis and limited resources, European states are redrawing boundaries of access and belonging. A timely example are recently introduced European resettlement and humanitarian admission programmes, admitting limited numbers of ‘particularly vulnerable’ refugees from countries of refuge. Categorisation practices are central in this process. In official policies and in daily frontline work, policy categories prioritise, include and exclude along the intersecting lines of inter alia nationality, gender, age or education. Thereby, they create inequalities and shape perceptions of who is most deserving of access or care, and who is considered undeserving or a risk. Taking Germany’s humanitarian admission programmes from Lebanon and Turkey as an example, the thesis follows categorisation practices throughout the complete transnational admission chain: from policy formulation in Germany, via refugee selection and pre-departure in countries of refuge, to refugee reception in German provinces and municipalities. Grounded in a triangulated methodology, including document analysis, interviews, and participant observations, the thesis reveals how categorisations get translated and transform from one institutional context to another, who gets prioritised at different steps in the process, and how actors normatively justify or contest categorisations and resulting inequalities. Fusing insights from Interpretive Policy Analysis, International Political Sociology and feminist theories of intersectionality, the thesis advances a dynamic and processual understanding of categorising, inclusion and exclusion. Moreover, it contributes to theorising the normative grammars actors deploy to justify categorisation practices and the inequalities they produce
Modulators of metabolism:Pathways to insulin resistance
Get PDFThe prevalence of obesity has increased worldwide the last several decades. Obesity is associated with complications such as type 2 diabetes, hypertension, and dyslipidemia, and as a result, obesity is associated with increased mortality. One of the major underlying mechanisms by which obesity leads to its complications is the development of insulin resistance, i.e. the diminished biological response to insulin. The only treatment modality that has been proven effective in the long term is bariatric surgery. In this thesis, we aimed to investigate some of the pathways and mechanisms that contribute to obesity-induced insulin resistance. In addition, we studied the effect of bariatric surgery-induced weight loss on some of these parameters as well as which clinical parameters predict the metabolic success of this type of surgery in the long term
Mongols in Mamluk eyes:Representing ethnic others in the medieval Middle East
Get PDFThis dissertation analyses the representation of the Mongols in the Mamluk sultanate of Egypt and Syria, c. 1250-1350 CE, the development of which took place against a complicated background. While the Mongols of the Ilkhanate were the Mamluks’ primary enemy, the Golden Horde was their most important ally. The Mamluks themselves, former military slaves, were predominantly of Turkic descent and were therefore considered to be closely related ethnically to the Mongols – some even were Mongols themselves. Given these circumstances, representations of the Mongols, a key Other for Mamluk era authors, were far from straightforward and unanimous.This dissertation emphasises how contemporary scholars were involved in processes of ethnic identification, categorisation and othering. By incorporating the Mongols into existing scholarly traditions, authors explained their (perceived) physical and mental characteristics, and by focusing on Mongol cultural elements (origin stories, laws) writers stressed their un-Islamic ways. They developed a discourse on the Mongols that generally tied in with the concerns and programme of the Mamluks. Different images were created for different groups of Mongols, with Islam playing a key role: the Ilkhanids were depicted as infidels even after their conversion to Islam; the Muslim credentials of the Golden Horde were emphasised even when its rulers were pagan. In a similar way, Mongols within the sultanate could be considered an integrated part of the Mamluk elite. Representations of the Mongols were thus actively constructed and used for various purposes in response to, and in interaction with, the sultanate’s complex ethnic and political contexts
State transformations in the global political economy::The rise of transnational state capital in the 21st century
Get PDFThis dissertation analyzes the rise of transnational state capital in the global political economy and its consequences for international politics. A standard reading of the rise of “state capitalism” in the last years suggests that it represents a counter-movement against neoliberal globalization. In this study, I challenge this reading and argue that it is not primarily state capitalist economies (like China or the BRICS), but rather state-owned capital that rises in the global political economy. It does so through the very opportunity structures neoliberal globalization itself created. The consequences for international politics are hence more nuanced than the standard “state capitalist challenge”-reading suggests: states rise as owners in the global political economy and thereby engage in forms of geoeconomic competition with other economic actors. In order to substantiate these arguments, the dissertation sets up and analyzes the largest existing firm-level dataset on cross-border state investment.The findings of this study show:(1) Which states are senders and targets of cross-border state investment and how they relate to each other within the global political economy.(2) The variety of different strategies states as transnational owners apply, from financial to more controlling strategies.(3) How the employment of these strategies leads to variegated effects on international politics in the form of geoeconomic competition; and which geographical areas are the hotspots of this type of competition.In sum, the project hence demonstrates how states become part of global markets; which strategies they employ to do so; and what consequences this rise has for international politics
Special Cases of the Orbifold Version of Zvonkine’s r-ELSV Formula
Get PDFWe prove the orbifold version of Zvonkine's r-ELSV formula in two special cases: The case of r = 2 (completed 3-cycles) for any genus g ≥ 0 and the case of any r ≥ 1 for genus g = 0
Lawfully using autonomous weapon technologies:A theoretical and operational perspective
Get PDFAutonomous weapon systems (AWS) have to be employed in conformity with international humanitarian law (IHL). On this, the international community has reached consensus. Less clear is how to translate this normative commitment into practice in the field. How are the technology’s end-users – field commanders – expected to exercise command-and-control when ordering AWS-attacks?This legal treatise adopts an operational approach and theorises on how commanders can use existing targeting frameworks to ensure that their use of AWS remains in compliance with the rules governing the conduct of hostilities. This research explored the following legal questions from a commander’s perspective:• How does one maintain control of AWS throughout a targeting cycle?• How does one make informed and reasoned deployment decisions, by analysing information related to the technical parameters of the AWS, characteristics of the operational environment, and enemy countermeasures?• Under which circumstances may AWS not be used under targeting rules, such as indiscriminate attack, proportionality and the duty to cancel/suspend?• What extra precautionary measures unique to AWS technology can and should be employed?• When is it militarily desirable to employ AWS (over other alternatives)?• Under what circumstances may criminal liability be attributed for AWS-related harm?This monograph has two core outputs, one academic and one practical. For the former, it offers new legal and doctrinal insights on the technology that is useful for future legal developments. For the latter, it provides efficient flowcharts that can be adopted by commanders, military organisations or policymakers to ensure IHL-compliant deployment of AWS
The retinal origin of congenital nystagmus
Get PDFThis thesis describes a revolutionary retinal mechanism leading to nystagmus in mouse models for CSNB. In patients with CSNB and nystagmus, mutations were found that are specifically present in the photoreceptor to ON-bipolar cell synapse, both pre- and postsynaptically. Here, we studied one presynaptic (Cav1.4) and two postsynaptic mutations (mGluR6nob3, Nyxnob) that cause CSNB. We found that all three mouse models show nystagmus and oscillating RGCs, but that they varied phenotypically between the three genotypes. All three mutations lead to an altered membrane potential of the ON-BCs and consequently of the AII ACs as well. The latter are then outside their normal working range and start to intrinsically oscillate. These oscillations are passed on to the RGCs, which also start to oscillate. This includes the ON-DSRGCs, that send an oscillatory retinal slip signal to the AOS, which consequently leads to compensatory, oscillatory eye movements, the nystagmus. The different phenotypes can thereby be explained by the difference in depolarization levels of the ON-BCs due to the different mutations