Leiden University Scholary Publications
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    Threading the needle: constraining the stellar content and dynamics of the Galactic Centre with hypervelocity stars

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    In this thesis we use state-of-the-art observations and simulations to provide the best constraints to date on the HVS ejection rate and constraints on the stellar content and dynamics at the GC, including the progenitor binary populations and their star formation history. The challenge in identifying HVSs is often the observational volume of the sample that is used, which is a common thread through most of the chapters in this thesis. We first attempt to identify new HVSs by increasing the number of stars with radial velocity solutions using the 220 million low resolution spectra provided by Gaia DR3, before switching to a method that looks for the fastest (>800 km/s) HVSs in all ~1.5 billion sources in Gaia. In Chapter 4 we combine these measurements with observations of the GC to perform a robust analysis linking the S-stars with the stars captured by the Hills mechanism and in the final chapter we use the newly released DESI DR1 MWS to further increase our observational footprint and search instead for HVSs ejected over billions of years that have remained bound to the Galaxy. We briefly summarise each chapter below.In Chapter 2 we start out by attempting to measure radial velocities from the aforementioned Gaia BP/RP spectra in Gaia DR3. Our goal is to increase the number of sources with 3D velocities, since that makes it more straightforward to identify HVS candidates. Using model grids of stellar spectra, we fit every available BP/RP spectrum and marginalise over all stellar parameters other than radial velocity. We find that BP/RP spectra in Gaia can be used to measure radial velocities, albeit at much lower precision compared to, for instance, Gaia RVS. We perform calibration of the radial velocities in colour-magnitude-extinction space and publish a catalogue of BP/RP measured radial velocities. Our extended catalogue, containing some 125M radial velocity measurements is to our knowledge the largest radial velocity catalogue to date. Despite the size of our catalogue, we find that identifying HVSs from our catalogue is non-trivial, due to the large nominal uncertainties and a fraction of sources with unreliable measurements.In Chapter 3 we follow a different approach to identify HVS candidates. Instead of only looking at stars with 3D velocity measurements, we use a novel method to select stars that appear to be travel on radial trajectories from the GC, which can be applied to all ~1.5 billion stars with astrometric solutions in Gaia. We create a catalogue of 600 HVS candidates, based on their proper motions, sky position, and colour and perform follow-up observations for about 200 of those using ground-based spectroscopic instruments. Because we use both northern and southern hemisphere telescopes, we can cover our HVS candidates across the sky. We use the non-detection of new HVSs among our 200 observed HVS candidates in combination with sophisticated simulations to significantly improve constraints on the ejection rate and mass function of HVSs and provide predictions for the undiscovered population of HVSs in Gaia.Chapter 4 in a way is the odd one out in this thesis, since we do not attempt to discover new HVSs. Instead we combine observations of the GC with our own observational catalogue described in Chapter 3 and compare to simulations to investigate if the Hills mechanism alone can explain the observed properties of the S-star cluster. We use realistic star formation histories for stars near the GC and simulate binary disruptions. We find that no single progenitor binary population can explain all the observed properties of both the S-star cluster and HVSs simultaneously. Instead, we find that at least two progenitor populations are required: an old population and a young population. Assuming that the young population is the CWD near Sgr A* and the old population undergoes Hills mechanism disruptions at a constant rate, we find that the recent star formation episode at the GC which formed the CWD has boosted the Hills mechanism disruption rate by about an order of magnitude compared to the background rate over the past ~10 Myr.Finally in Chapter 5 we again aim to identify new HVSs by going to an even larger potential discovery space: stars ejected from the GC that have remained bound to the Galaxy. Since HVS ejections will have been happening for billions of years and a significant fraction of these is expected to remain bound to the Galaxy, a population of stars ejected from the GC should have accumulated in the stellar halo. Using the recently released DESI DR1 MWS survey data, we aim to statistically identify an overdensity of high metallicity stars on low angular momentum orbits, characteristic of stars ejected from the GC. Although we obtain a null-detection for a GC ejected population of stars, we use this null-detection to put upper limits on the ejection rate of stars from the GC over the past ~5 Gyr, which is ejection model independent. Galaxie

    Exploration of renal space: navigating injury and repair through spatial omics

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    This thesis explores how cellular metabolism shapes kidney injury and repair, using advanced spatial metabolomics to map metabolic processes directly within the tissue. By applying mass spectrometry imaging and new computational strategies, it reveals that metabolism is a crucial player in both acute and chronic settings of kidney injury. A central finding is that early in diabetes, the proximal tubule S3 segment undergoes distinct membrane lipid remodeling. This shift reduces membrane stability and makes this segment especially vulnerable, identifying PT-S3 as a key early site of diabetes-induced metabolic alterations. Methodological advances are another major contribution. This thesis establishes practical protocols for spatial dynamic metabolomics, enabling researchers to visualize not only which metabolites are present, but how actively they are produced. Applied to renal cell carcinoma, this approach captured the Warburg effect in single cells in situ. Finally, the work reveals that after acute kidney injury, metabolic disturbances extends in patches of injury. Even seemingly healthy epithelial cells become metabolically impaired when located within an injured niche, marked by disrupted succinate and fatty-acid metabolism. These findings highlight the importance of metabolic resuscitation of the injury microenvironment. LUMC / Geneeskund

    Microbial footprints of tomato domestication

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    Although plant domestication has significantly altered crop genetics and phenotypes, its effects on the taxonomic and functional diversity of plant-associated microbiomes are not well understood. This thesis investigates how the tomato domestication has influenced the diversity, structure, and functional potential of root-associate microbiomes by integrating field studies, controlled experiments, and quantitative genetics. Field exploration of the wild tomato Solanum pimpinellifolium in its native habitat in Sourthern Ecuador revealed a deterministic rhizosphere microbiome dominated by Enterobacteriaceae, Rhizobium, Fusarium, and Aspergillus. Bacterial metagenomic evidence showed traits that support adaptation to harsh environments. Experiments comparing wild and domesticated tomatoes grown in native, agricultural, and greenhouse soils demonstrated that both plant genotype and soil environment influence rhizosphere composition with domesticated tomato displaying microbiomes aligned with managed soils. These shifts suggest that domestication has inadvertently reduced beneficial microorganisms and microbial functions related to motility, chemotaxis and stress response, which were observed in their wild counterparts. Further analyses showed that the wild tomato relies on its native soil microbiome. Specifically, Actinobacteriota such as Actinoplanes, provided protection against the endemic insect Prodiplosis longifila. These bacteria exhibited functional traits associated with secondary metabolism and nutrient transport. Finally, using a recombinant inbred line population, we identified plant genomic regions associated with the differential recruitment of key bacterial taxa, such as Cellvibrio in wild and Streptomyces in domesticated tomato. These associations revealed reciprocal links between plant and bacteria regarding plant nutrient uptake, stress tolerance, and metabolic functions. Together, these findings demonstrate that domestication has reshaped tomato–microbiome interactions by altering microbial diversity and functions that are crucial for plant stress resilience. This work highlights the importance of reintegrating beneficial native microbial partners into breeding programs to support more resilient and sustainable agricultural systems.Ecuadorian National Secretariat of Higher Education, Science, Technology and Innovation – SENESCYT, scholarship number CZ07-000440-2018Microbial Biotechnolog

    Comparison of Levi-Civita connections in noncommutative geometry

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    Number theory, Algebra and Geometr

    Actions speak louder than words: assessing the democratic accountability of Europe's new industrial policy

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    The politics and administration of institutional chang

    Unveiling inequity: diversity and power in collaborative care networks

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    This dissertation aims to critically understand how intersecting aspects of diversity shape the collaboration between professionals and carers in care networks surrounding care recipients with acquired brain injury and a migration background. A disconnection in collaborative care becomes visible, highlighting a persistent mismatch between stakeholder perspectives on what constitutes for adequate collaboration. Othering and epistemic injustice are explicitly recognized by care recipients and carers when dealing with assumptions and (un)conscious bias from professionals. Carers explicitly emphasized having to deal with discriminatory practices, based on their cultural and religious backgrounds. At the same time, professionals often attribute problems in collaboration to carers, while they do not always acknowledge their own role in that difficult collaboration. By embracing intersectionality, professionals and policymakers can challenge (un)conscious assumptions and recognize both difference and sameness amongst care recipients and carers. Critical reflexivity and ongoing dialogue are required to enable an inclusive way of collaboration. This is an ongoing process of reciprocal learning between care recipients, carers, and professionals. Sustainable change in healthcare requires commitment from policymakers, educators, and professionals to embed diversity-responsive practices throughout all levels of care and educational programs of healthcare and social work professionals.This PhD thesis was made possible with financial support from: 1) a doctoral grant for lecturers from the Dutch Research Council (nwo promotiebeurs voor leraren), project number 023.011.009, and 2) a grant from the Centre of Expertise Urban Vitality, Amsterdam University of Applied Sciences.LUMC / Geneeskund

    Novel targets in the liver to treat cardiometabolic diseases

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    Obesity is a growing worldwide epidemic, affecting more than 0.89 billion adults by 2022, and is projected to increase by nearly 70% by 2035. Consequently, the incidence of obesity-induced cardiometabolic diseases has markedly increased, becoming a major health problem and severely impacting quality of life and threatening long-term health outcomes worldwide, despite the availability of current therapeutic strategies. This highlights the urgent need for new treatment approaches. Therefore, in this thesis, we investigated novel therapeutic targets for combating cardiometabolic diseases, especially metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerotic cardiovascular disease (ASCVD). As the liver is central in regulating lipid metabolism and inflammation, strongly affecting MASLD and ASCVD development, these targets were mainly liver-targeted. Overall, our findings revealed three novel therapeutic targets, including liver X receptor (LXR), hepatic lipase (HL), and ATP-binding cassette transporter A6 (ABCA6). Specifically, desmosterol-induced LXR activation via DHCR24 inhibition suppresses inflammation to prevent MASLD, while enhanced phospholipase activity of HL and abundance/activity of hepatic ABCA6 may reduce atherogenic lipids to decrease ASCVD. Collectively, this thesis provides valuable insights into the therapeutic potential of these targets, facilitating further investigation and accelerating their translational applications in humans for combating cardiometabolic diseases.LUMC / Geneeskund

    Obstetric hemorrhage: improving care by collaborating across borders

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    Postpartum hemorrhage (PPH) is a major, largely preventable cause of severe maternal morbidity and mortality in high-income countries. This thesis investigates whether international differences in severe maternal outcomes due to PPH can be partly explained by variations in second- and third-line management strategies. Using quantitative and qualitative benchmarking between France and the Netherlands, two countries with comparable healthcare quality but different outcomes, the research explores how clinical practice influences results.The studies demonstrate substantial variation in national guidelines regarding prevention, diagnosis, treatment thresholds, uterotonics, uterus-sparing interventions, transfusion strategies, and overall guideline quality. Earlier and more aggressive use of second-line treatments and uterus-sparing interventions in France may partly explain its lower incidence of severe outcomes compared with the Netherlands, although high hysterectomy rates warrant caution.Further analyses identify improvable care factors in maternal deaths due to PPH, particularly delays in diagnosis and treatment, suboptimal surgical skills during caesarean sections, and organisational shortcomings. The thesis highlights the value of international collaboration, standardised definitions, high-quality evidence-based guidelines, and repeated audit cycles. It concludes with recommendations to improve prevention, timely intervention, surgical training, and cross-border data sharing to optimise maternal outcomes after postpartum hemorrhage.Canon, Medical Systems Nederland, Chipsoft, Stichting Oranjekliniek, Bridea Medical, Safe Motherhood Series, ICT-HCTSLUMC / Geneeskund

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