Thiosugars: reactivity, methodology and applications

Carbohydrates, alongside proteins and nucleic acids, constitute a crucial and versatile family of biomolecules present in all life forms. They manifest as monosaccharides, oligosaccharides, and polysaccharides, covalently bonded to proteins and fats. Carbohydrates are integral to plant and arthropod cell walls and traditionally viewed as the primary source and storage of energy, but also play a vital role in many fundamental biological processes. To study the structure and biological activity of specific carbohydrates, it is essential to synthesize them in a pure and well-defined form, as current natural extraction techniques are often limiting.The work of this thesis is focused on a specific type of glycomimetics: thiosugars, i.e. sugar analogues which have their endocylic oxygen replaced by a sulfur atom. These analogues are of interest because of their unique stability and stereoelectronic effects, which closely mimick their natural O-counterparts. The glycosidic linkage of thioglycosides (i.e. 4-S-furanosides and 5-S-pyranosides) shows improved resistance towards chemical and enzymatic hydrolysis.Bio-organic Synthesi

Understanding deep meta-learning

The invention of neural networks marks a critical milestone in the pursuit of true artificial intelligence. Despite their impressive performance on various tasks, these networks face limitations in learning efficiently as they are often trained from scratch. Deep meta-learning is one approach to improve the learning efficiency by leveraging prior knowledge and experience. Whilst many succesful deep meta-learning techniques have been proposed, our understanding of the performance of these methods remains limited. In this dissertation, we delve deeper into the underlying principles of these algorithms, and aim to gain a comprehensive understanding of why certain algorithms succeed while others fall short. This allows us to design enhanced deep meta-learning algorithms and reason about the impact of specific design choices on the performance of different algorithms. Moreover, we investigate the integration of theoretical principles into meta-learning algorithms to improve their performance. Overall, we make a small step toward a better understanding of deep meta-learning algorithms, paving the way for more robust and principled meta-learning techniques with broader applicability and superior performance. Computer Systems, Imagery and Medi

Applications of multisource data-based dynamic modeling to cell-cell signaling and infectious disease spreading

The emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic mechanisms underlying cell-cell signaling and infectious disease spreading is crucial for effective disease prevention and treatment. As science and technology advance, the availability and diversity of observational and experimental data related to these biological processes continue to grow. In this thesis, we integrate multisource data with dynamic modeling to investigate the biological mechanisms of Notch signaling in biological development and to develop prevention and control strategies for infectious diseases.Analysis and Stochastic

Setting the stage for decision-making on nature-based solutions for coastal climate adaptation

Nature-based solutions (NbS) are fast becoming the norm for multifunctional coastal climate adaptation to increased sea-level rise. However, informing decision-makers about NbS presents ongoing challenges. This study set out to identify and explore the information requirements at different stages of the decision-making process of coastal NbS. Developing and applying a novel methodological approach, we analysed the values and indicators discussed in four key decision-making stages: the advocacy, political, bureaucratic and provisioning stages. Applied to a mega beach nourishment in the Netherlands, our study identified substantial differences in information requirements across the decision-making stages. Most notably, the values and indicators discussed shifted from being abstract to becoming increasingly specific and concrete as the stages progressed. Our findings emphasize the importance of recognizing the distinct stages of decision-making and tailoring the content and level of abstraction of information accordingly. Additionally, they suggest that future changes in the content and concretisation of the information required for decision-making on coastal NbS can be anticipated and prepared for. By distinguishing and understanding the decision-making stages in NbS, this study bridges a longstanding gap between decision-making and NbS studies, thereby allowing for improving the fairness, implementation, evaluation and comprehension of trade-offs of coastal NbS. This study progresses the understanding of the information required for planning, implementing, evaluating and managing coastal NbS, advancing multifunctional coastal climate adaptation for shores worldwide.NWO17595Environmental Biolog

Local phytochrome signalling limits root growth in light by repressing auxin biosynthesis

NWO14212Plant science

Taking up space: waste and waste labor in developing South Korea

“Taking Up Space: Waste and Waste Labor in Developing South Korea” examines South Korean development experiences through the remnants of its industrialization and modernization processes, including material waste, excess labor, or surplus population. I juxtapose the history of informal waste pickers with the transformation of waste management and the reconfiguration of its labor during the period from the 1960s to the early 1990s. By connecting the material, social, and symbolic dimensions of waste, I demonstrate how waste shaped their stigma and social position, degraded the urban environment as much as it deteriorated their living and working conditions, and brought social and environmental forces that further drove their marginalization. The case studies—waste picker camps and Seoul’s Nanjido Landfill—illustrate how concepts such as informality, precarity, and societal marginalization have been historically mediated and grounded in individuals’ lives during the country’s compressed development process.This study demonstrates how the production of marginalized populations and the disregard for their labor practices served to consolidate the developing nation-state and its middle-class citizens. It argues that the informal labor at the urban periphery was instrumental in the development process and should be recognized as legitimate labor rather than mere subsistence activities. Waste pickers not only served as agents of development but also as a precedent for precarious workers in modern Korea. The prevalence of waste pickers in contemporary South Korea indicates a diachronic implication of this dissertation, as their labor remains crucial for urban conditions while simultaneously establishing an urban form of precarity.Asian Studie

Making diabetes care fit: insights, strategies and support

Globally, over 537 million adults are living with diabetes mellitus. Treatment of diabetes poses a large burden on patients, since it relies predominantly on the patient’s daily self-management. Therefore, providing the patient with a care plan that fits seamlessly in one’s daily routines, is in line with their values and preferences and does not overburden their capacities, is of major importance. In order to make diabetes care fit, clinicians and patients need to collaborate and share their knowledge and experience. One possible approach to this collaboration is shared decision making (SDM). In SDM, patients and clinicians partner up and work together to decide on the best available healthcare strategy for the individual patient, taking into account both the best available evidence, and the patient’s preferences, needs and context. This thesis aimed to explore patient and clinician efforts towards making diabetes care fit. In this exploration we aimed to provide insight in the factors driving the decision making process, discuss various strategies to tailor SDM to the patient’s situation, needs and preferences, and explore ways to support the patient and the patient-clinician partnership in diabetes care.Department of Biomedical Data Sciences, section of Medical; Decision Making (LUMC); ChipSoftLUMC / Geneeskund

Global China's human touch?: The internationalisation of Chinese NGOs

The thesis aims to provide a systematic, structured and evidence-based view of the internationalisation of Chinese NGOs and examine their role in Chinese international development by primarily studying 28 Chinese NGOs based on fieldwork, interviews and analysis of organizational discourses. The thesis has shown that the major characteristic of the autonomy of Chinese NGOs is that the Chinese state’s influence does not come directly from its interventions in the operations of Chinese NGOs as there are limited direct policies, funding and other operational intervention from the Chinese government related to internationalisation. Instead, the Chinese state’s influence is embedded in the existing regulatory system regarding NGO registration and supervision and in the sources of legitimacy for internationalisation, a phenomenon dubbed as “embedded internationalisation”. The process of Chinese NGOs’ internationalisation is not sufficiently autonomous from the influence of the Chinese state and corporations and, thus, cannot offer a viable alternative to China’s mainstream international development landscape. Instead, Chinese NGOs have played a complementary role, as they have enriched the varieties of China’s aid and development cooperation and promoted China’s soft power.Asian Studie

Breaking barriers: unraveling response mechanisms to immunotherapy in breast cancer

A deeper understanding of the parameters driving response and resistance to immunotherapy is needed to improve the low response rates observed in breast cancer patients. Research into immunotherapy response has predominantly focused on T cells, however effective immune responses require tightly regulated crosstalk between innate and adaptive immune cells. By combining profiling of blood and tumors from metastatic breast cancer patients with mechanistic studies in mouse models, we uncovered the critical role of eosinophils in immunotherapy response, and we provide proof-of-principle for eosinophil engagement to enhance immunotherapy efficacy. Focusing on resistance mechanisms to immunotherapy, we demonstrate that neoadjuvant immunotherapy triggers persistent and systemic regulatory T cell activation which blunts therapeutic efficacy against metastatic spread of breast tumors. In addition, we demonstrate that neutrophils in the tumor microenvironment pose a barrier to immunotherapy response through T cell suppression. Lastly, we demonstrate that combining the immunomodulatory agent PD1-IL2v with cisplatin is a powerful approach to induce a broad activation of systemic and intratumoral adaptive and innate immunity, resulting in effective immunotherapy responses. Overall, this work identifies several key players and their interconnectivities in anti-tumor immunity and tumor-induced immunosuppression that may be therapeutically exploited to improve immunotherapy responses for breast cancer patients. LUMC / Geneeskund

Metabolomics assisted with stable-isotope labeling: exploring neuronal metabolism related to Parkinson’s disease

The progressive loss and degeneration of dopaminergic neurons is a major pathological hallmark of Parkinson's disease (PD). The onset and progression of PD can be triggered by multiple risk factors, for instance, genetic mutation, environmental exposure, and aging. Each factor may cause common or unique metabolic disturbances, ultimately converging into a complex metabolic disorder with diverse clinical phenotypes. Through metabolome analysis, the full picture of the metabolic landscape depicting a biological system can be revealed. Metabolites function as key elements and direct read-outs of a system’s functional status. Alterations in metabolite concentrations are informative for inferring and understanding underlying metabolic activity. In addition, stable isotope labeling techniques coupled with metabolomics can bring us an extra-dynamic vision of the metabolic landscape. Changes in labeling patterns of metabolites help identify alterations with metabolic fluxes through pathways. This thesis aimed to develop a comprehensive analytical strategy for characterizing the metabolic activity related to PD neurodegeneration, especially focused on the improvement in metabolome coverage and data quality, facilitating the use of stable isotope labeling in in-depth metabolism investigations, and developing a computational workflow for metabolic flux analysis. These methods were applied to investigate metabolic dysregulation of dopaminergic neurons due to genetic and environmental factors.Pharmacolog