International Migration, Integration and Social Cohesion online publications
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Pulsed Dye Laser in psoriasis:A nerve-wrecking event?
Get PDFThis thesis investigates the mechanisms and effects of Pulsed Dye Laser (PDL) therapy in the treatment of psoriasis, aiming to clarify the underlying mechanisms of PDL's therapeutic effects. The research encompasses a range of experimental approaches, including in vitro, ex vivo, in silico, and in vivo studies. The first chapters focus on the impact of hyperthermia on various cell types, while the later chapters present clinical patient studies that explore the detailed morphology of the perivascular network in the skin and the changes it undergoes following PDL treatment. The original hypothesis of the work that PDL destructs perivascular nerves in psoriasis could not be confirmed, yet 3D histological sections suggested that PDL may inflict damage upon the CD3+ immune cell clusters right below the dermo-epidermal junction. Thus, PDL may cause thermal damage that leads to a functional, but not morphological, alteration of nerve fibers and possibly also cause thermal damage to immune cell clusters around the vasculature of the skin
Self driving labs for the optimization of photochemical processes
Get PDFThe integration of automation, artificial intelligence (AI), and robotics into synthetic chemistry has ushered in a new era of self-driving laboratories (SDLs) capable of accelerating reaction optimization and chemical discovery. This thesis presents RoboChem, an advanced SDL platform designed for the optimization of photochemical processes. By leveraging Bayesian optimization and automated experimentation, RoboChem efficiently explores chemical space, reducing the number of required experiments while improving reproducibility and scalability.Chapter 1 introduces the field of SDLs, emphasizing their potential to overcome inefficiencies in traditional organic synthesis. Chapter 2 details the development of the RoboChem platform, including its hardware and software architecture, fluidic automation, and AI-driven decision-making. Chapter 3 applies RoboChem to synthetic photochemistry, demonstrating its capability for optimizing reaction conditions, light intensity, and catalyst loadings. Chapter 4 expands the platform’s utility to automated substrate selection and functional group tolerance testing, enabling high-throughput dataset generation for machine learning applications.By automating photochemical optimization, RoboChem enables rapid discovery of efficient reaction conditions, minimizes human intervention, and enhances safety. The findings in this thesis highlight the transformative role of SDLs in modern chemistry, paving the way for broader applications in reaction discovery, materials science, and beyond
How human are our machines?:Rethinking how we communicate with social robots
Get PDFAs robots make their way into unstructured contexts, they are required to have social characteristics to effectively communicate with users, posing the question: To what extent do existing theoretical frameworks apply to interaction with modern social robots? Our theoretical understanding of interaction with media agents is derived from the Computers-Are-Social-Actors (CASA) framework. Since its conception, there have been significant advancements to media agents themselves, people’s understanding of media agents, and the nature of interaction between these media agents and people, which has transformed people’s understanding and expectations of media agents from what CASA predicted.This dissertation conducted two cross-sectional experiments and one longitudinal survey. The first study focused on the effect of interdependency and a robot’s display of augmented cognitive capabilities on human-robot team behaviour and found that when participants perceived the robot as a teammate, they did not experience more team affinity or behaviour than when they did not perceive it as a teammate. The second study found that when being helped by a robot, participants did not reciprocate the helpful behaviour, even with the presence of a single humanlike social cue (a face). The third study was based on data from an eight-week study, in which children interacted with a social robot within their own home. It did not find any robust long-term patterns between social presence and perceived companionship.These findings indicate the need to update theoretical frameworks such that they can better explain social responses in (long-term) interactions between advanced social robots and experienced users
Making the connection:Improving the clinical and regulatory management of leukodystrophies
Get PDFLeukodystrophies comprise a group of rare neurogenetic disorders primarily affecting the white matter of the nervous system. Patients typically suffer from severe and progressive neurological disabilities. Advancements in diagnostics and pathophysiological understanding pave the way for therapy development. At the start of this PhD trajectory, the management perspective of metachromatic leukodystrophy (MLD) and vanishing white matter (VWM) was about to change: imminent approval of gene therapy for MLD and start of the first therapeutic trial in VWM. In this thesis, the role of international collaborations and patient registries is illustrated. We initiated the MLD initiative, a collaborative network and registry for MLD supported by a grant from the Dutch Healthcare Institute, and used the VWM consortium and VWM registry to advance therapeutic development and disease management in VWM
Bouwen langs de Maas:Huizen in Limburgse steden circa 1200-1600
Get PDFHet proefschrift ‘Bouwen langs de Maas’ behandelt de bouwpraktijk van stedelijke huizen in de late middeleeuwen in de steden Maastricht, Sittard, Roermond en Venlo. Het onderzoek richt zich op de factoren die het uiterlijk van deze huizen bepalen. Er wordt eerst gekeken naar de historische context van de steden, zoals politieke omstandigheden, de specifieke stadsgeschiedenis, handelscontacten en naar de heersende bouwvoorschriften en de organisatie van bouwambachten. Vervolgens wordt per stad de ruimtelijke ontwikkeling geschetst en de positie van de huizen daarin. In Hoofdstuk 3 wordt aandacht besteed aan de verschillende huisvormen die in de steden voorkomen: woontorens, huizen met een hofachtige aanleg (‘poorten’), diepe huizen, dubbelhuizen en dubbelbrede huizen. Hoofdstuk 4 is gewijd aan de bouwmaterialen die kenmerkend zijn voor de huizenbouw in de vier steden tot ongeveer 1600 n. Chr.. Hier wordt gekeken naar de herkomst, verspreiding en toepassing van bouwmaterialen, zoals kolenzandsteen, mergel, baksteen en eikenhout. Hoofdstuk 4 behandelt ook de constructie van de huizen. Zowel vakwerkbouw als steenbouw komen aan bod, evenals de verstening van de huizen en constructieve elementen zoals kelders, balklagen en kapconstructies. In hoofdstuk 5 wordt de vormgeving van de huizen besproken, zowel die van vroege steenbouw, als die van vakwerkhuizen in Maastricht en Sittard en bakstenen huizen in Roermond en Venlo. Het proefschrift wordt afgesloten met hoofdstuk 6, waarin de resultaten van de onderzoeksthema’s in een bredere, interregionale en internationale context worden geplaatst
Een kwestie van uitvoering:De gemeente Amsterdam als instrument van de Duitse repressie 1940-1945
Get PDFTijdens de Duitse bezetting van Nederland is de gemeente Amsterdam betrokken geweest bij de onderdrukking, uitsluiting en vervolging van haar eigen burgers. Zo zijn Joodse Amsterdammers door het Bevolkingsregister geregistreerd, door het Bureau voor Sociale Zaken naar werkkampen gestuurd en door de Gemeentepolitie, het Trambedrijf en de Gemeentelijke Gezondheidsdienst naar de deportatiecentra en -treinen vervoerd. Dit roept vragen op naar de verantwoordelijkheid en motieven van de toenmalige bestuurders. De keuzes die destijds door de burgemeester, wethouders en hoofden van gemeentelijke diensten zijn gemaakt worden in dit onderzoek geanalyseerd, met elkaar vergeleken en in een bredere context geplaatst. Waarschijnlijk hebben meerdere factoren een rol gespeeld in de vergaande medewerking van ‘gewone’ Amsterdamse gemeentelijke functionarissen aan de Duitse repressie. Hoewel die functionarissen na de oorlog diverse formele rechtvaardigingen voor hun samenwerking met de vijand hebben gegeven, is de uitkomst van dit onderzoek dat de houding van Nederlandse bestuurders en ambtenaren bovenal bepaald lijkt te zijn geweest door de vrees voor Duits geweld en het besef van eigen machteloosheid. De geschiedenis van het Amsterdamse gemeentelijke apparaat tijdens de Duitse bezetting kan geïnterpreteerd worden als een geschiedenis van menselijke en ambtelijke tekortkomingen. Tegelijkertijd mag echter niet uit het oog verloren worden dat dit apparaat te maken kreeg met een bezetter die over de nodige dwangmiddelen beschikte waarmee hij zijn wil kon trachten door te drijven
Rescue alkaline phosphatase in ischemic kidney damage:Target then treat
Get PDFThis thesis centers exploring kidney transplantation and acute kidney injury (AKI), with a particular focus on the therapeutic potential of alkaline phosphatase (AP) to mitigate ischemia-reperfusion injury (IRI) by modulating the host and injury response. To better understand AKI following transplantation, we investigated early graft dysfunction across donor types using data from the Dutch National Transplant Registry. The analysis compared delayed graft function (DGF), slow graft function (SGF), and immediate graft function (IGF) in kidneys from donation after brain death (DBD) and donation after circulatory death (DCD). While long-term graft survival was similar, early dysfunction patterns and clinical implications varied, underscoring the need for tailored post-transplant care.In two biomarker studies, we examined AKI in critically ill patients with COVID-19 and sepsis. Findings suggest that these are distinct entities, with urinary CCL14 serving as a potential marker of severe host-response dysregulation closely tied to AKI development. We also explored AP’s therapeutic potential in a narrative review, particularly for sepsis-associated AKI, where preclinical studies showed promise, though clinical efficacy remains unproven.To explore clinical translation, we administered AP in a porcine model of donor kidney storage to assess its capacity to preserve cellular metabolism and reduce injury. Finally, in a pilot study, we administered bovine-derived AP (bRESCAP) to living donor kidney transplant recipients, evaluating its safety, feasibility, and impact on graft function one year post-transplant, using measured glomerular filtration rate (mGFR) and kidney injury biomarkers
Fishing for autonomy:The making of Indian fisheries science
Get PDFA troubled relation exists between the realms and practices of ‘science’ and ‘politics’ across the world in the 21st century, and presents itself as a struggle for autonomy between these realms, even within ‘applied’ state-funded scientific fields such as fisheries science. This study of fisheries science asks, “can science ever be far from politics, and should it?"Disciplinary actions, both internal and external aimed at curtailing autonomy, have existed across organisations, in various nations and across periods of time. Such practices as well as resistances to them have shaped these very fields today. How can we historically and sociologically understand struggles for autonomy of and within Indian fisheries science? This thesis interrogates the unexamined claim to modernity seen in contemporary struggles for autonomy within scientific organisations. It takes fisheries science and the historical shaping of the Central Marine Fisheries Research Institute (CMFRI) in India as the empirical grounds for constructing its case. The manuscript shows the value of engaging Bourdieu’s field theory with postcolonial science studies. This thesis deploys this framework to make visible the ways in which power and dominance operate through diverse practices within Indian fisheries science. The thesis argues that autonomy of the field and of its practitioners is neither an objective phenomenon nor a wholly subjective experience. Rather, India’s institutionalised fisheries science, may be seen as a historical enactment of politics by other means; a multiplicity of postcolonial practices which both limit and encourage autonomy of individuals and the field itself
Cracking tolerance:Examining tissue microenvironments in early arthritis
Get PDFThe study of human biopsies provides great insights into the specialized tissue environments that maintain immune homeostasis in the body. Direct comparisons between healthy and diseased tissues enhance our understanding of the mechanisms underlying disease onset and progression. Rheumatoid Arthritis (RA) is a chronic autoimmune disease of unknown origin which is characterized by synovial joint inflammation which if left untreated leads to pannus formation causing pain, swelling and bone damage. In this thesis we first explored immune perturbations in the lymph node and synovium in both preclinical and established RA. The findings in this thesis revealed an enrichment of neutrophils within the lymph node of established arthritis patients. Lymph node analysis of RA patients and individuals at risk of developing disease (RA-risk) and uncovered a type I interferon signature in RA-risk individuals and a T follicular helper cell profile in RA patients. Synovial tissue analysis of RA-risk individuals and RA patients revealed increased DNA damage and a reduced capacity for DNA repair in synovial fibroblasts. The final chapters focused on the crosstalk between lymph node fibroblasts and T cells and its impact on immunological tolerance. Lymph node fibroblasts were shown to uniquely maintain regulatory T cells in a HLA-DR dependent manner. This mechanism was not perturbed in RA patients and RA-risk individuals despite a reduced expression of HLA-DR on ex-vivo LN fibroblasts. Collectively, the chapters of this thesis present compelling evidence for alterations in the immunological landscape of the lymph node and synovium during the earliest phases of autoimmunity
Pathogenic insights into immune-mediated sclerosing cholangiopathies:From autoantibody formation to cholangiocellular defence mechanisms
Get PDFIn immune-mediated cholestatic liver diseases bile flow is impaired due to biliary tree damage induced or perpetuated by an excessive immune-response often against self-antigens. Primary sclerosing cholangitis (PSC) and IgG4-related cholangitis (IRC) are characterized by inflammation and consequent sclerosing (scarring) of the bile ducts, which leads to cirrhosis and need for liver transplantation when inadequately treated. To arrive at new, increasingly selective treatment strategies that slow down disease progression, it is important to understand the potentially disrupted underlying regulatory mechanisms in cholangiocytes. This thesis focusses on identifying protective machinery and autoantigens in cholangiocytes, and investigates the potentially pathogenic role of autoantibodies against these targets in PSC and IRC. We found that: 1) The ion transporters SLC9A1, SLC26A2 and SLC26A6 protect cholangiocytes from toxic bile acids and may be transcriptionally regulated by peroxisome proliferator-activated receptors. 2) Individuals with PSC and IRC have autoantibodies against carbonic anhydrase (CA) enzymes, which catalyse the reaction CO2 + H2O ⇌ HCO3- + H+. In particular, anti-CA5B autoantibodies are highly prevalent and functionally inhibit the human enzyme. 3) Individuals with IRC possess autoantibodies against laminin 511, an extracellular matrix protein substantially secreted by cholangiocytes that enhances barrier function and protects against T cell-induced barrier dysfunction. Notably, the autoantigens galectin-3 and prohibitin 1 do not have clear protective functions in cholangiocytes.This suggests that certain – but not all – autoantibodies in PSC and IRC may disrupt protective mechanisms of cholangiocytes comprising: HCO3- production and secretion, a sensory component, and epithelial barrier tightness, collectively termed the “cholangiocyte defence triangle”.<br/