Leiden University Scholary Publications
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Machine learning assisted classification of staphylococcal biofilm maturity
Get PDFAn increasing incidence of device-related, biofilm-associated infections has been observed in clinical practice worldwide. In vitro biofilm models are essential to study these burdensome infections and to design and test potential new treatment approaches. However, there is considerable variation in in vitro biofilm models, and a generally accepted systematic description of biofilm maturity - apart from incubation time - is lacking. Therefore, we proposed a scheme comprised of 6 different classes based on common topographic characteristics, i.e., the substrate, bacterial cells and extracellular matrix, identified by atomic force microscopy (AFM), to describe biofilm maturity independent of incubation time. Evaluation of a test set of staphylococcal biofilm images by a group of independent researchers showed that human observers were capable of classifying images with a mean accuracy of 0.77 +/- 0.18. However, manual evaluation of AFM biofilm images is time-consuming, and subject to observer bias. To circumvent these disadvantages, a machine learning algorithm was designed and developed to aid in classification of biofilm images. The designed algorithm was capable of identifying pre-set characteristics of biofilms and able to discriminate between the six different classes in the proposed framework. Compared to the established ground truth, the mean accuracy of the developed algorithm amounted to 0.66 +/- 0.06 with comparable recall, and off-by-one accuracy of 0.91 +/- 0.05. This algorithm, which classifies AFM images of biofilms, has been made available as an open access desktop tool.Immunogenetics and cellular immunology of bacterial infectious disease
Provincializing “new” diplomatic history: an interdisciplinary manifesto
Get PDFA group of young scholars revisit the aims, nature, and purpose of New Diplomatic History.Colonial and Global History 1200-presen
Global research initiative for patient screening on MASH (GRIPonMASH) protocol: rationale and design of a prospective multicentre study
Get PDFAnalytical BioScience
Forever young: how AHL15 delays developmental phase transitions to prevent ageing in plants
Get PDFThe AT-Hook Nuclear Localized 15 (AHL15) gene belongs to a plant-specific gene family of DNA-binding proteins. Overexpression of AHL15 in Arabidopsis thaliana delays developmental phase transitions whereas its loss of function causes a slight acceleration. In this thesis, the regulation of developmental phase transitions and the current knowledge on AHL genes is described in chapter 1. Chapter 2 describes the relation between the aerial rosette phenotype in several Arabidopsis ecotypes and the expression of AHL15, its close relative AHL20 and the genes FLC, SOC1, and SPL15. The results of chapter 2 show that the expression of FLC, SOC1, and AHL20 predict aerial rosette formation. In chapter 3, a simple method of chlorophyll quantification based on digital images is presented, which is applied in chapter 4 to study how AHL15 represses leaf senescence. Chapter 4 describes how AHL15 directly represses leaf senescence by regulating expression of ORESARA1 and several CYTOKININ OXIDASE genes, resulting in a delay in cytokinin degradation and subsequently a delay in leaf senescence. Finally, chapter 5 investigates the genome-wide binding sites of AHL15, and shows that AHL15 can modulate gene expression without changing chromatin accessibility on a local scale, most likely via affecting the 3D structure of chromatin.Enza Zaden; Deliflor; Dümmen OrangePlant science
Beyond the paradigm of unity: embedded minilateralism in European foreign policy
Get PDFHistory and International Studies 1900-presentInstitutions, Decisions and Collective Behaviou
Les leçons des Muses: créer une mémoire de la Grèce dans les manuels scolaires franco-néerlandais du XVIe siècle
No full textMedieval and Early Modern Studie
Beyond grief: the raison d’être of interactive personality constructs of the dead
Get PDFGlobal Challenges (FGGA
Design of branched swainsonines as selective Colgi alpha-mannosidase II inhibitors
Get PDFDesign and synthesis of two 3-substituted swainsonine derivatives with the aim to improve the potency and selectivity towards Golgi alpha-mannosidase II.Netherlands Organisation for Scientific Research (NWO)Bio-organic Synthesi
Acetaminophen attenuates pathological pain through a mechanism that requires CB1 cannabinoid receptors and the enzyme diacylglycerol lipase in mice
Get PDFAcetaminophen (APAP) is commonly used as a pain and fever reliever, but its mechanisms remain unclear. Conflicting evidence implicates the endocannabinoid system in the effects of APAP. We tested the hypothesis that the analgesic effects of APAP were dependent upon both CB1 cannabinoid receptors and diacylglycerol lipase (DAGL), an enzyme which catalyzes formation of the endocannabinoid 2-arachidonoylglycerol. We examined the impact of APAP, administered in the presence and absence of DAGL inhibitors, on mechanical hypersensitivity in mice using models of inflammatory (induced by intraplantar injection of complete Freunds adjuvant (CFA)) and post-surgical (induced by incisional injury) pain. Pharmacological specificity was assessed using global (Rimonabant, AM251) and peripherally restricted (AM6545) CB1 antagonists. APAP produced a dose-dependent attenuation of inflammation-induced mechanical hypersensitivity, but did not alter peripheral edema in the CFA-injected paw. APAP also attenuated mechanical hypersensitivity in mice with incisional injury. The DAGL inhibitors, RHC-80267 or DO34, attenuated the anti-allodynic effects of APAP in both models of pain. CB1 receptor antagonists (Rimonabant and/or AM251) suppressed the antinociceptive effect of APAP in both pain models. The peripherally-restricted CB1 antagonist AM6545 did not alter the anti-allodynic effects of APAP. We also assessed the impact of APAP on tail-flick antinociception, locomotor behavior, and body temperature. APAP produced hypothermia and hypolocomotion at the highest dose, but these effects were not blocked by RHC-80267 or AM251. APAP did not produce tail flick antinociception. Our studies demonstrate that the analgesic effects of APAP observed in mouse models of pathological pain require both DAGL and CB1 activation. Our findings support a potential mechanism of APAP-induced analgesic action involving the enzyme DAGL and CB1 receptors.Molecular Physiolog