Leiden University Scholary Publications
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Enhancing autonomy and efficiency in goal-conditioned reinforcement learning
Get PDFReinforcement learning is a framework that enables agents to learn in a manner similar to humans, i.e. through trial and error. Ideally, we would like to train a generalist agent capable of performing multiple tasks and achieving various goals. Goal-conditioned reinforcement learning is a step toward training such an agent. The goal-conditioned reinforcement learning framework comprises four steps: 1) defining the goal space; 2) selecting an interesting goal for the agent; 3) the agent learning to reach the goal; 4) the agent post-exploring. In the thesis, we proposed four research questions and focused on three parts of the goal-conditioned reinforcement learning framework.Algorithms and the Foundations of Software technolog
Pierre de L'Estoile et la révolte des Pays-Bas (1576-1598)
Get PDFEurope 1000-1800: Collective Identities and Transnational Network
Popular religion
Get PDFThe chapter focuses on forms of ritual of non-organized religions, "popular religion," which includes shamanism, but draws attention to rituals performed without the intervention of shamans: for instance by housewives, villagers, and professional groups, such as ginseng collectors, woodsmen, carpenters, sailors and fishermen.Asian Studie
Visible: discovering the impact of research conducted by universities of applied sciences
Get PDFThis dissertation aims to address the following questions: What are the requirements for evaluating the research impact created by Dutch Universities of Applied Sciences’ (UASs) research?How can these requirements be applied within the context of the goals of Dutch UASs?It sets out to discover the requirements for evaluating the research impact made by UAS research and explore how these can be implemented in real-life within the current policy landscape. Answering these questions has resulted in two distinct yet interlinked segments as we moved from theory to practice. Firstly, we sought to delineate the rules governing the evaluation of UAS research impact. Secondly, we analysed the current practices within the contextual playing field in which Dutch UASs find themselves and experimented with applying the requirements to the impact evaluation process of Dutch UAS research. Our results culminate in recommendations for conducting UAS research impact evaluation as well as discussing how our conclusions can be applied by researchers, administrators and policy-makers in practice.Saxion University of Applied SciencesMerit, Expertise and Measuremen
Mast cells in advanced atherosclerosis: from human plaque stability to new therapeutic targets
Get PDFIn this thesis, the role of mast cells in atherosclerosis and novel therapeutic strategies to inhibit atherosclerosis progression are discussed. The first part of the thesis specifically focuses on the relation between mast cells and advanced human atherosclerotic plaque characteristics. The second part of the thesis focuses on identifying and examining new potential therapeutic targets to treat atherosclerosis. In chapter 2, we implemented a flow-cytometry-based method to identify mast cells and its activation status in advanced human plaques. We evaluated the relation between mast cells and key features of human plaque stability. In chapter 3, we further investigated the link between mast cells and plaque stability in a large patient cohort from the BiKe biobank. In particular, we examined the role of mast cells in plaque calcification via vascular smooth muscle cells. In the second part of the thesis, we used single-cell RNA sequencing data of human plaques to identify novel therapeutic targets in atherosclerosis. In chapter 4, we examined the therapeutic potential of Bruton’s Tyrosine Kinase in atherosclerosis by treating Ldlr-/- mice with a small molecule inhibitor in early and advanced experimental atherosclerosis. Chapter 5 explores Leukemia Inhibitory Factor Receptor signaling as novel target in the treatment of atherosclerosis. Biopharmaceutic
Venous thromboembolism in patients with glioblastoma: cancer and coagulation in concert
Get PDFGlioblastoma, IDH-wildtype, is the most common primary brain malignancy among adults. Due to its aggressive nature and hypercoagulable state, the risk of venous thromboembolism (VTE) is particularly high, with an incidence of up to 10-30% per year. Although the underlying genetic and cellular mechanisms are increasingly understood, current prophylactic treatment strategies sparsely include risk scores that aid in risk prediction at the individual level. Sequencing of tumor material, which is standard of care for tumor diagnostics, directly provides insight in genetic risk factors present. In combination with measurement of procoagulant extracellular vesicles (EVs), the patient’s individual hypercoagulable risk profile can be determined, which should be at the basis for personalized thromboprophylaxis. In glioblastoma, there are two procoagulant factors expressed by tumor cells that have been linked to VTE: Tissue Factor (TF), the initiator of extrinsic coagulation, and podoplanin, a transmembrane glycoprotein involved in platelet aggregation. This thesis focuses on the genetic and cellular background of VTE in glioblastoma patients, with a specific interest in the role of TF.Trombosestichting NederlandLUMC / Geneeskund
Should states use social media to warn civilians in armed conflict?
Get PDFThe essay argues that in the current conditions of the online information ecosystem, communications via social media to issue effective warnings ahead of military operations cannot discharge a state's legal obligation pursuant to Article 57(2)(c) Additional Protocol I.In a high-stress situation like intense military operations, any communication channel used must be reliable and trustworthy for the recipients of critical, life-saving information. This is not the case if (1) the same party to the conflict is responsible for rendering the digital communication environment physically (by attacking infrastructures) or substantially (by spreading false or misleading information) unstable; (2) officials belonging to the party use the same channels to communicate war aims that suggest evacuation orders to be pretextual; and (3) the party uses the same channels/platforms to deceive the adversary.Exploring the Frontiers of International LawEffective Protection of Fundamental Rights in a pluralist worl
Circulating FGF21 is lower in South Asians compared with Europids with type 2 diabetes mellitus
Get PDFObjectiveInflammation contributes to the development of type 2 diabetes mellitus (T2DM). While South Asians are more prone to develop T2DM than Europids, the inflammatory phenotype of the South Asian population remains relatively unknown. Therefore, we aimed to investigate potential differences in circulating levels of inflammation-related proteins in South Asians compared with Europids with T2DM. MethodIn this secondary analysis of three randomized controlled trials, relative plasma levels of 73 inflammation-related proteins were measured using an Olink Target Inflammation panel and the serum fibroblast growth factor 21 (FGF21) concentration using an ELISA kit in Dutch South Asians (n = 47) and Dutch Europids (n = 49) with T2DM. ResultsOf the 73 inflammation-related proteins, the relative plasma levels of six proteins were higher (stem cell factor, caspase-8, C-C motif chemokine ligand 28, interferon-gamma, sulfotransferase 1A1 and cystatin D; q-value <0.05), while relative levels of six proteins were lower (FGF21, human fibroblast collagenase, interferon-8, C-C motif chemokine ligand 4, C-X-C motif chemokine ligand 6 and monocyte chemoattractant protein-1; q-value <0.05) in South Asians compared with Europids. Of these, the effect size of FGF21 was the largest, particularly in females. We validated this finding by assessing the FGF21 concentration in serum. The FGF21 concentration was indeed lower in South Asians compared with Europids with T2DM in both males (-42.2%; P < 0.05) and females (-58.5%; P < 0.001). ConclusionRelative plasma levels of 12 inflammation-related proteins differed between South Asians and Europids with T2DM, with a significantly pronounced reduction in FGF21. In addition, the serum FGF21 concentration was significantly lower in South Asian males and females compared with Europids. Whether low FGF21 is an underlying cause or consequence of T2DM in South Asians remains to be determined. Clinical trial registrationClinicalTrials.gov (NCT01761318, registration date 20-12-2012; NCT02660047, registration date 21-03-2018; and NCT03012113, registration date 06-01-2017).Metabolic health: pathophysiological trajectories and therap
