International Migration, Integration and Social Cohesion online publications
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Flowing with intelligence:Machine learning driven screening, optimization and prediction of photocatalytic reactions in flow
Get PDFThis thesis presents the development of intelligent, machine learning-guided workflows for the optimisation, screening, and prediction of chemical reactions. The work bridges the fields of chemistry, automation, and data science, with the aim of improving how experimental data is collected and used to drive discovery in synthetic chemistry.The thesis spans three main projects. The first focuses on RoboChem, an automated flow platform designed for self-optimisation and scale-up of photocatalytic reactions. By integrating Bayesian optimisation, RoboChem demonstrated efficient enhancement of reaction yield and throughput in a reproducible and data-rich manner.The second project explores a high-throughput experimentation workflow for reaction screening. Using an initial dataset and a Random Forest model, the method predicts promising reaction conditions in unexplored chemical space. This approach successfully identified new C(sp³)–C(sp³) bond-forming reactions.The third project centres on reaction prediction, particularly using data collected via RoboChem. Substrates were clustered to guide targeted experimentation, generating a dataset that enabled reaction outcome predictions under various conditions. While further data is needed for broader generalisation, the results show the predictive potential of RoboChem-generated data
Fracture behavior of contemporary ceramics produced by digital manufacturing
Get PDFContinuous efforts have been made to enhance the quality of dental ceramics to improve the longevity of permanent restorations, which is the key to achieving long-term success for prosthetic treatment. When a failure occurs, restoration replacement often necessitates additional costs and supplementary interventions accompanied by sacrificing healthy dental tissues. Therefore, reducing the failure rate and improving the lifetime of ceramic restorations have always been the common goal for dental clinicians and technicians. With the development of new ceramic materials and digital manufacturing techniques, it is vital to have sufficient scientific knowledge of the materials and manufacturing to make the proper clinical decision and manufacture the restorations using appropriate techniques with optimized design to minimize fracture risk. This thesis aims to provide valuable insights into the understanding and application of contemporary dental ceramics and manufacturing techniques, as well as the optimization of manufacturing processes for enhancing their mechanical properties, reliability, and longevity
Beyond indeterminacy:On reputation and interpretation in international law
Get PDFThis dissertation explores the role of reputation in the practice of interpretation in international law. First, it argues that reputation has been fundamentally misconceptualised in legal scholarship, and proposes a more sociologically-inspired understanding of the concept. It then argues that in the frequent absence of centralized interpretation and enforcement in international law, reputation has an important role in processes of stabilization and change in the practice of interpretation: participants in that practice care about what others think of them, and therefore meaningfully orient their interpretive expressions towards each other. Interpretations of international law stabilize and change as a result. It is by way of such processes that indeterminacy makes way for relative determinacy, and international law is ‘made’ and ‘remade’. The project explores interpretation under the spell of reputation in two case studies: the interpretation of the principle of self-determination as codified in the UN Charter, and the interpretation of the ‘political prohibition clause’ in the World Bank’s Articles of Agreement
Health outcome after preterm birth:A microbiota perspective
Get PDFIn this dissertation, we seek to understand health after preterm birth from a gut microbiota perspective. Neonatal antibiotic exposure and fecal metabolic and microbial changes were examined as potential risk factors for acute and chronic conditions after preterm birth. In addition, techniques for fecal odor analysis and spatial orientation of gut bacteria were explored in preterm infants. Our results might contribute to strategies to predict, prevent, recognize and treat necrotising enterocolitis, neonatal sepsis and meningitis, and long-term non-communicable diseases
Gear shifting in Archaca and Eukarya
Get PDFThis thesis investigates the different levels of coupling in Archaea and Eukarya using a systems biology approach that integrates modelling, experiments, and theory. Specifically, chapter 2 summarizes the bidirectional coupling between cellular metabolism and the cell cycle machinery in budding yeast, which involves complex metabolic and biosynthetic reactions necessary for building new cells. Chapter 3 focuses on investigating the effect of the Cyclin B/Cdk1 complex on some yeast metabolic enzymes using in vitro phosphorylation assays, finding that Fba1 and Pgk may be phosphorylated by Cdk1. Additionally, this study examines the possible effect of Sic1 on the activities of three important metabolic enzymes, finding that Sic1 may have a slight negative effect on Hxk2 activity. The thesis also describes a minimal computer model of the cell cycle that predicts timely mitotic cyclin Clb2 expression and validates the model through chromatin immunoprecipitation experiments. The last two chapters focus on understanding the phenomenon of gear shifting in the hyperthermophilic archaeon Saccharolobus solfataricus. Chapter 5 describes gear shifting both at the substrate-level phosphorylation around glyceraldehyde-3 phosphate dehydrogenase, or at the membrane-linked oxidative phosphorylation with the involvement of alternative terminal oxidases. Specifically, with application of kinetic models, chapter 6 shows that the ATP/ADP ratio could well be the force driving the shifting of the organisms from the high-gear GAPDH plus PGK route to the low-gear GAPN. Overall, the study contributes to a better understanding of the coupling between metabolic and cell cycle machinery and the phenomenon of gear shifting in extremophilic organisms
Shaping susceptibility:The role of SIX8 and TOPLESS in Fusarium wilt disease
Get PDFThe Fusarium oxysporum (Fo) species complex causes Fusarium wilt disease in a wide range of economically important crops, including tomato, cotton, banana, spinach, lettuce, melon, and ornamentals such as chrysanthemum and tulip. Current management strategies are often environmentally harmful, expensive, and unsustainable. A viable alternative is to the use of genetically resistant plant varieties. This thesis identifies members of the small TOPLESS (TPL) gene family as key Susceptibility (S) genes for Fo infection. Two specific TPL proteins directly interact with the Fo-secreted effector protein, SECRETED IN XYLEM 8 (SIX8). CRISPR/Cas9-mediated knockout of these TPL genes in both tomato and Arabidopsis thaliana conferred near-complete resistance to Fo, confirming their role as S genes. The SIX8 gene is present in 14 Fo isolates with distinct host specificities, while TPL genes are conserved across all land plants, suggesting that this resistance strategy could be broadly applicable across different crop species. TPL proteins function as transcriptional co-repressors, leading us to hypothesize that SIX8 promotes disease by manipulating host transcription. To investigate this, we generated A. thaliana lines expressing SIX8 and discovered that the immune receptor SNC1 monitors both TPL and TPL-RELATED 1 (TPR1). Furthermore, expression of SIX8 in a snc1 null mutant background, followed by transcriptome profiling revealed biological pathways that are potentially targeted by the pathogen during infection.</p
The rheostats of the immune response:Post-transcriptional regulation of gene expression by RNA-binding proteins in adaptive immunity
Get PDFThe adaptive immune system protectsthe host from pathogens and cancer through the actions of B and T lymphocytes.B cells produce antibodies, while CD4⁺ and CD8⁺ T cells secrete effector molecules,including inflammatory cytokines such as Tumor Necrosis Factor (TNF),Interferon gamma (IFN-g), and Interleukin-2 (IL-2). To perform their functions, T and Bcells differentiate into specialized subsets, a process governed by geneexpression programs that are tightly regulated at both transcriptional andpost-transcriptional levels. RNA-binding proteins (RBPs) are keypost-transcriptional regulators that control gene expression by modulating mRNAsplicing, stability, translation, and localization.This thesis demonstrates that theRBP ZFP36L2 plays a crucial role in limiting IFN-g production duringprolonged T cell activation. ZFP36L2 binds AU-rich elements in the 3’UTR of IfngmRNA, promoting its degradation and thereby reducing IFN-g output. Incontrast, its paralog ZFP36L1 acts earlier during T cell activation, andcombined deletion of ZFP36L1 and ZFP36L2 induces superior cytokine productionin T cells. We further show that ZFP36L1 and ZFP36L2 cooperate to control cellcycle progression and survival in resting T cells. Furthermore, transcriptomicprofiling reveals that RBPs are highly expressed in T and B cells and undergodynamic changes during differentiation. Lastly, we performed a CRISPR-Cas9screen in primary human T cells to identify RBPs that modulate T cellactivation.Together, the contents of thisthesis underscore the central role of RBPs in T and B cell biology and highlightseveral RBPs as potential targets for modulating T cell function fortherapeutic purposes
Toward opportunities for inclusive GP-specialty training:On building bridges over the unspoken undercurrents
No full textMigration has led to rapidly increased diversity in population demographics, necessitating a healthcare system that addresses its population's varied cultural and social needs. Given primary care's central role, these developments require a GP-workforce that reflects and respects this diversity. However, despite this requirement, ethnic minority GP-trainees in the Netherlands seem more at risk of being assessed as underperforming than their majority peers.This dissertation investigates barriers and facilitators faced by these trainees, examining the impact on their professional development and identifying strategies for fostering an inclusive training environment. The research comprises four complementary studies: Quantitative Analysis of Underperformance Assessments: An analysis of 1,700 trainees revealed that those from minority backgrounds are at a significantly higher risk of being labeled as 'underperforming,' even after adjusting for age and gender.Lived Experiences of Minority GP-Trainees during their 'Educational Journey': In-depth interviews with 14 trainees highlighted experienced bias, microaggressions, and a lack of belonging within predominantly 'white' institutions.Coping Strategies of these trainees: Trainees reported various coping mechanisms, including emotional distancing, religious support, and peer networking, which may put them at risk for isolation and hinder professional growth.Intervention Development: Seven interventions were proposed and co-designed with trainees and faculty. These include mandatory DEI training for all stakeholders, DEI ambassadors, and a significant voice for minority trainees in their curriculum. The researchers underscore the need for continuous evaluation and adjustment in GP-specialty training programs to ensure a genuinely inclusive educational environment that reflects the diversity of the broader society.</p
Identità e contesti nella committenza del cardinale di Senigallia Marco Vigerio (1505-1516)
No full textLa tesi ricerca analizza il contesto di committenza artistica e culturale gravitante attorno alla corte del cardinale Marco Vigerio (1505-1516). Nonostante l'importanza del personaggio, Vigerio ha ricevuto scarsa attenzione storiografica, sia per l'assenza di una tradizione storiografica relativa alla famiglia Vigerio, originaria di Savona, sia per la sua marginalizzazione operata dagli storici della Controriforma, che ne hanno restituito un'immagine scialba e parziale. La ricerca mette radicalmente in discussione questo orientamento critico. Le informazioni recuperate attraverso l’individuazione, lo studio e l’interpretazione delle fonti letterarie e archivistiche mettono a fuoco, in primo luogo, il ruolo di primo piano ricoperto dal cardinale, personalità di spicco, tra Quattro e Cinquecento, dello stretto entourage familiare del pontefice Giulio II, e figura di raccordo tra le reti internazionali dell’ordine francescano e i circoli umanistici e intellettuale italiani ed europei. La tesi prende quindi in esame gli interessi figurativi e la committenza artistica del prelato. Se lo studio dei suoi scritti teologici rivela l’interesse del personaggio rispetto a teorie e pratiche artistiche, l’analisi stilistica, iconografica e sociologica delle opere mette in luce la capacità del cardinale di utilizzare la committenza artistica come veicolo delle proprie istanze religiose e culturali, come mezzo di promozione personale, nonché come strumento funzionale al consolidamento della propria rete di clientela e alla promozione delle strategie propagandistiche del papato. Infine, viene preso in esame il ruolo rivestito da Vigerio nelle strategie artistiche di Giulio II. Il cardinale, impegnato nell’organizzazione della propaganda pontificia e principale promotore del Concilio Lateranense, è coinvolto nel piano di riassetto urbano avviato da Giulio II e nei cantieri artistici e architettonici promossi dal pontefice. Sulla base di questi elementi, la ricerca avanza l’ipotesi che l’insigne teologo francescano sia da riconoscere nell’intellettuale in dialogo con Raffaello per l’elaborazione del programma iconografico dell’affresco raffigurante la Disputa del Sacramento. Elaborato sotto il profilo iconografico alla stregua di un’Apocalisse, il tema teologico della Rivelazione, soggetto dell’affresco vaticano, viene pertanto interpretato alla luce della funzione escatologica assegnatagli dalla teologia francescana. L’iconografia dell’affresco trova in questo modo una sua coerente collocazione all’interno della retorica profetica utilizzata dalla propaganda pontificia
Hybrid luminescent systems based on rare-earth-doped upconversion nanoparticles:Mechanisms and wide range temperature sensing
Get PDFLanthanide-doped upconversion nanoparticles (UCNPs) are promising candidates for advanced optical applications, yet their efficiency remains a critical challenge. This thesis presents a systematic study to enhance the luminescence and functionality of UCNPs through energy transfer engineering, host lattice design, and nanocomposite strategies.The energy transfer mechanism in the Yb3+-Ho3+ system by tailoring core-shell-shell nanostructures is explored and optimized, which enable efficient cooperative sensitization upconversion (CSU), especially at cryogenic temperatures. Building on this, a photonic nanostructure incorporating polymethyl methacrylate (PMMA) opal photonic crystals is designed to further enhance the emission of this system via photonic bandgap modulation, resulting a 4,300-fold upconversion luminescence enhancement at 80 K and enabling high-sensitivity cryogenic thermometry.Next, a highly sensitive temperature probe based on a heavily doped Er³⁺ system is developed, where cross-relaxation effects provide reliable and ultra-sensitive luminescence thermometry. To further boost the upconversion performance, alkaline-earth-based cubic host matrices (M1-xErF2+x, M = Ca, Sr, Ba) are introduced to modify the host-dopant interactions. Among them, SrErF5@SrYF5 nanoparticles exhibit over 8-fold enhanced emission and pronounced thermal responsiveness.Finally, a novel composite is constructed by integrating cubic-phase BaYbF5:Tm3+ UCNPs with CsPbBr3 perovskite quantum dots. The excellent lattice match facilitates energy transfer and produces dual-mode optical output, demonstrating potential in multifunctional nanophotonics.Together, this work advances the design of high-performance UCNP platforms and broadens their applications in low-temperature sensing, optical devices, and hybrid nanophotonic systems.</p