330 research outputs found

    De stijl van betogen

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    Rede gehouden door Prof.dr. Ton van Haaften ter gelegenheid van zijn afscheid als hoogleraar Taalbeheersing van het Nederlands aan de Universiteit Leiden op maandag 22 november 2021Language Use in Past and Presen

    Een avondje stappen of nachtelijke escapades?

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    In rechtszaken speelt ethos een belangrijke rol: om haar zaak te winnen, probeert elke partij het eigen ethos te versterken en dat van de tegenpartij te ondermijnen. Om een rechter te overtuigen is het van strategisch belang dat de partijen hun eigen aandeel in de zaak zo positief mogelijk kleuren en het aandeel van de tegenpartij zo negatief mogelijk. Cruciaal daarbij is de vraag of een partij betrouwbaar is geweest en verantwoordelijk heeft gehandeld. Advocaten proberen het antwoord op die vraag vaak te sturen met allerlei subtiele formuleringskeuzes. Dit illustreren we aan de hand van de zaak 'Van Gelder'.Language Use in Past and Presen

    Strategisch manoeuvreren met stijl

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    Binnen het kader van de uitgebreide pragma-dialectiek wordt ervan uitgegaan dat taalgebruikers, wanneer zij iemand willen overtuigen, hun argumentatieve zetten zo kiezen en vormgeven dat zij strategisch manoeuvreren tussen enerzijds de wens om te voldoen aan eisen van redelijkheid en anderzijds de wens om zo effectief mogelijk te zijn. Presentatiemogelijkheden vormen een van de drie aspecten van strategisch manoeuvreren. Talige stijlmiddelen vormen een belangrijk onderdeel van deze presentatiemogelijkheden. De analyses van de wijze waarop taalgebruikers strategisch manoeuvreren met stijlmiddelen zijn echter veelal ad hoc: een systematische analyse van stijl ontbreekt vaak.Dit artikel heeft twee nauw met elkaar verbonden doelstellingen. Ten eerste willen we laten zien hoe een systematische analyse van stijlmiddelen kan worden geĂŻntegreerd in een pragma-dialectische analyse van argumentatief taalgebruik. Daartoe maken we gebruik van methodische inzichten uit de taalkundige stilistiek. Ten tweede willen wij betogen dat de door ons voorgestelde integratie van uitgebreide pragma-dialectiek en taalkundige stilistiek voor beide benaderingen waardevol is. Onze doelstellingen werken we uit aan de hand van een juridische casus.Language Use in Past and Presen

    An integrated bioinformatics approach to improve two-color microarray quality-control: impact on biological conclusions

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    Omics technology used for large-scale measurements of gene expression is rapidly evolving. This work pointed out the need of an extensive bioinformatics analyses for array quality assessment before and after gene expression clustering and pathway analysis. A study focused on the effect of red wine polyphenols on rat colon mucosa was used to test the impact of quality control and normalisation steps on the biological conclusions. The integration of data visualization, pathway analysis and clustering revealed an artifact problem that was solved with an adapted normalisation. We propose a possible point to point standard analysis procedure, based on a combination of clustering and data visualization for the analysis of microarray data

    Peribiliary glands are key in regeneration of the human biliary epithelium after severe bile duct injury

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    Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking. We, therefore, developed a novel ex vivo model using precision-cut slices of extrahepatic human bile ducts obtained from discarded donor livers, providing an intact anatomical organization of cell structures, to study spatiotemporal differentiation and migration of PBG cells after severe biliary injury. Post-ischemic bile duct slices were incubated in oxygenated culture medium for up to a week. At baseline, severe tissue injury was evident with loss of luminal epithelial lining and mural stroma necrosis. In contrast, PBG remained relatively well preserved and different reactions of PBG were noted, including PBG dilatation, cell proliferation and maturation. Proliferation of PBG cells increased after 24 h of oxygenated incubation, reaching a peak after 72 h. Proliferation of PBG cells was paralleled by a reduction in PBG apoptosis and differentiation from a primitive and pluripotent (Nanog+/Sox9+) to a mature (CFTR+/secretin receptor+) and activated phenotype (increased expression of HIF-1α, Glut-1, and VEGF-A). Migration of proliferating PBG cells in our ex vivo model was unorganized, but resulted in generation of epithelial monolayers at stromal surfaces. CONCLUSION: Human PBG contain biliary progenitor cells and are able to respond to bile duct epithelial loss with proliferation, differentiation, and maturation to restore epithelial integrity. The ex vivo spatiotemporal behaviour of human PBG cells provides evidence for a pivotal role of PBG in biliary regeneration after severe injury. This article is protected by copyright. All rights reserved

    Hoe zien de alinea’s van onze leerlingen eruit?: Over de kenmerken van alinea’s in e-mails en betogende teksten van havoleerlingen

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    Secondary school teachers expect students to write comprehensible paragraphs in their texts. However, an explicit way of teaching to write a paragraph doesn’t exist. This article describes a text analytic study of compliance with language norms in paragraphs in two genres: e-mails with a request and persuasive texts. It addresses the question to what extent the paragraphs of thirteen- and seventeen-year-old students comply with the paragraph norms constructed on the basis of Dutch professional advisory books. Our findings indicate that students in Dutch secondary school have difficulty writing adequate paragraphs. Our results additionally suggest that students’ paragraph skills increase over time and vary across genres.Teaching and Teacher Learning (ICLON

    Partner independent fusion gene detection by multiplexed CRISPR-Cas9 enrichment and long read nanopore sequencing

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    Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment. Fusion gene partner choice and breakpoint-position promiscuity restricts diagnostic detection, even for known and recurrent configurations. Here, we develop FUDGE (FUsion Detection from Gene Enrichment) to accurately and impartially identify fusions. FUDGE couples target-selected and strand-specific CRISPR-Cas9 activity for fusion gene driver enrichment - without prior knowledge of fusion partner or breakpoint-location - to long read nanopore sequencing with the bioinformatics pipeline NanoFG. FUDGE has flexible target-loci choices and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in one sequencing run. We observe on-average 665 fold breakpoint-site enrichment and identify nucleotide resolution fusion breakpoints within 2 days. The assay identifies cancer cell line and tumor sample fusions irrespective of partner gene or breakpoint-position. FUDGE is a rapid and versatile fusion detection assay for diagnostic pan-cancer fusion detection

    The Citrullinated and MMP-degraded Vimentin Biomarker (VICM) Predicts Early Response to Anti-TNF alpha Treatment in Crohn's Disease

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    Background: In Crohn's disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor- (TNF) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage. Aim: The aim of this study was to investigated whether early changes in the VICM (citrullinated and matrix metalloproteinase-degraded vimentin) biomarker were associated with response to anti-TNF treatment in patients with CD. Methods: Serum VICM levels were measured by ELISA in 2 independent cohorts of CD patients (n=42) treated with anti-TNF (infliximab or adalimumab). Response was determined by achieving clinical remission (Harvey Bradshaw Index<5). Results: Compared with baseline, VICM serum levels were reduced by anti-TNF in the infliximab cohort (week 6 and 14) and in the adalimumab cohort (week 8). VICM was lower in the responders compared with the nonresponders [infliximab: Week 6, P<0.05; area under the curve (AUC)=0.90; adalimumab: Week 1, P<0.01 (AUC=0.91), and week 8, P<0.05 (AUC=0.86)], and were able to predict response to treatment after 1 week of treatment with an odds ratio of 42.5. Conclusions: The VICM biomarker was time dependently reduced in CD patients responding to anti-TNF treatment. We suggest that VICM may be used as a marker for monitoring early response to anti-TNF in patients with CD
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