European language equality

This deep dive on data, knowledge graphs (KGs) and language resources (LRs) is the final of the four technology deep dives, as data as well as related models are the basis for technologies and solutions in the area of Language Technology (LT) for European digital language equality (DLE). This chapter focuses on the data and LRs required to achieve full DLE in Europe by 2030. The main components identified – data, KGs, LRs – are explained, and used to analyse the state-of-the-art as well as identify gaps. All of these components need to be tackled in the future, for the widest range of languages possible, from official EU languages to dialects to non- EU languages used in Europe. For all these languages, efficient data collection and sustainable data provision to be facilitated with fair conditions and costs. Specific technologies, methodologies and tools have been identified to enable the implementation of the vision of DLE by 2030. In addition, data-related business models and data-governance models are discussed, as they are considered a prerequisite for a working data economy that stimulates a vibrant LT landscape that can bring about European DLE.peer-reviewe

Lipid Alterations in Experimental Murine Colitis: Role of Ceramide and Imipramine for Matrix Metalloproteinase-1 Expression

BACKGROUND:Dietary lipids or pharmacologic modulation of lipid metabolism are potential therapeutic strategies in inflammatory bowel disease (IBD). Therefore, we analysed alterations of bioactive lipids in experimental models of colitis and examined the functional consequence of the second messenger ceramide in inflammatory pathways leading to tissue destruction. METHODOLOGY/PRINCIPAL FINDINGS:Chronic colitis was induced by dextran-sulphate-sodium (DSS) or transfer of CD4(+)CD62L(+) cells into RAG1(-/-)-mice. Lipid content of isolated murine intestinal epithelial cells (IEC) was analysed by tandem mass spectrometry. Concentrations of MMP-1 in supernatants of Caco-2-IEC and human intestinal fibroblasts from patients with ulcerative colitis were determined by ELISA. Imipramine was used for pharmacologic inhibition of acid sphingomyelinase (ASM). Ceramide increased by 71% in chronic DSS-induced colitis and by 159% in the transfer model of colitis. Lysophosphatidylcholine (LPC) decreased by 22% in both models. No changes were detected for phosphatidylcholine. Generation of ceramide by exogenous SMase increased MMP-1-protein production of Caco-2-IEC up to 7-fold. Inhibition of ASM completely abolished the induction of MMP-1 by TNF or IL-1beta in Caco-2-IEC and human intestinal fibroblasts. CONCLUSIONS/SIGNIFICANCE:Mucosal inflammation leads to accumulation of ceramide and decrease of LPC in the intestinal epithelium. One aspect of ceramide generation is an increase of MMP-1. Induction of MMP-1 by TNF or IL-1beta is completely blocked by inhibition of ASM with imipramine. Therefore, inhibition of ASM may offer a treatment strategy to reduce MMP-1 expression and tissue destruction in inflammatory conditions

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes

Spurenlesen.

Der Charakter der Sammlungs- und Objektforschung lässt sich unter anderem mit dem Begriff „Spurenlesen“ fassen. „Spur“, der erste Bestandteil des Wortes, verankert die Sammlungs- und Objektforschung fest im materiellen Bereich. Ohne materiellen Träger keine Spur. Doch wird die Spur erst durch den Akt des ‚Lesens‘ zur Spur. Die interessegeleitete Interpretation macht aus dem Geschmack ein Differenzierungsmerkmal zur Unterscheidung von essbar und giftig, aus einer Blattform ein Identifizierungsmerkmal einer Pflanze, aus einer Instrumentenanzeige einen wissenschaftlichen Messwert. Spurenlesen ist so verstanden nicht nur archaisches Überbleibsel, Orientierungs- und Überlebenstechnik aus einer vorwissenschaftlichen Zeit, sondern gleichermaßen Grundlage wissenschaftlicher Tätigkeit. Dieser Band vereint 15 Beiträge von Nachwuchswissenschaftlerinnen und Nachwuchswissenschaftlern aus den Bereichen Anthropologie, Archäologie, Religions- und Medienwissenschaft, der Kunst-, Musik-, Technik- und Wissenschaftsgeschichte sowie der Restaurierungswissenschaft, Forensik und Medizin. Sie haben sich mit jeweils unterschiedlichen Fragestellungen und Analysemethoden auf Spurensuche begeben. Die Reflexion über forschungsleitende methodische Aspekte und theoretische Herangehensweisen objektbasierter Forschung bildet einen gemeinsamen Referenzpunkt der Beiträge.Peer Reviewe

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis