24 research outputs found
Workbench for creating block-based environments
Block-based environments are visual-programming environments that allow users to create programs by dragging and dropping blocks that resemble jigsaw puzzle pieces. These environments have proven to lower the entry barrier of programming for end-users. Besides using block-based environments for programming, they can also help edit popular semi-structured data languages such as JSON and YAML. However, creating new block-based environments is still challenging; developers can develop them in an ad-hoc way or using context-free grammars in a language workbench. Given the visual nature of block-based environments, both options are valid; however, developers have some limitations when describing them. In this paper, we present Blocklybench, which is a meta-block-based environment for describing block-based environments for both programming and semi-structured data languages. This tool allows developers to express the specific elements of block-based environments using the blocks notation. To evaluate Blocklybench, we present three case studies. Our results show that Blocklybench allows developers to describe block-based specific aspects of language constructs such as layout, color, block connections, and code generators
Early expansion of allergen-responsive LAP<sup>+</sup> B regulatory cells in allergic rhinitis but not in allergic asthma subjects during allergen immunotherapy
Early expansion of allergen-responsive LAP<sup>+</sup> B regulatory cells in allergic rhinitis but not in allergic asthma subjects during allergen immunotherapy
Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge
Innate mononuclear phagocytic system (MPS) cells preserve mucosal immune homeostasis. We investigated their role at nasal mucosa following allergen challenge with house dust mite. We combined single-cell proteome and transcriptome profiling on nasal immune cells from nasal biopsies cells from 30 allergic rhinitis and 27 non-allergic subjects before and after repeated nasal allergen challenge. Biopsies of patients showed infiltrating inflammatory HLA-DRhi/CD14+ and CD16+ monocytes and proallergic transcriptional changes in resident CD1C+/CD1A+ conventional dendritic cells (cDC)2 following challenge. In contrast, non-allergic individuals displayed distinct innate MPS responses to allergen challenge: predominant infiltration of myeloid-derived suppressor cells (MDSC: HLA-DRlow/CD14+ monocytes) and cDC2 expressing inhibitory/tolerogenic transcripts. These divergent patterns were confirmed in ex vivo stimulated MPS nasal biopsy cells. Thus, we identified not only MPS cell clusters involved in airway allergic inflammation but also highlight novel roles for non-inflammatory innate MPS responses by MDSC to allergens in non-allergic individuals. Future therapies should address MDSC activity as treatment for inflammatory airway diseases.</p
The intestinal expulsion of the roundworm Ascaris suum is associated with eosinophils, intra-epithelial T cells and decreased intestinal transit time
Ascaris lumbricoides remains the most common endoparasite in humans, yet there is still very little information available about the immunological principles of protection, especially those directed against larval stages. Due to the natural host-parasite relationship, pigs infected with A. suum make an excellent model to study the mechanisms of protection against this nematode. In pigs, a self-cure reaction eliminates most larvae from the small intestine between 14 and 21 days post infection. In this study, we investigated the mucosal immune response leading to the expulsion of A. suum and the contribution of the hepato-tracheal migration. Self-cure was independent of previous passage through the liver or lungs, as infection with lung stage larvae did not impair self-cure. When animals were infected with 14-day-old intestinal larvae, the larvae were being driven distally in the small intestine around 7 days post infection but by 18 days post infection they re-inhabited the proximal part of the small intestine, indicating that more developed larvae can counter the expulsion mechanism. Self-cure was consistently associated with eosinophilia and intra-epithelial T cells in the jejunum. Furthermore, we identified increased gut movement as a possible mechanism of self-cure as the small intestinal transit time was markedly decreased at the time of expulsion of the worms. Taken together, these results shed new light on the mechanisms of self-cure that occur during A. suum infections
Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics
Item does not contain fulltextBACKGROUND: Mutations in complement factor H (CFH), factor I (CFI), factor B (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and autoantibodies against factor H (alphaFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (CFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS). METHODS: Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome. RESULTS: In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xalphaFH, of which five had CFHR1/3); four patients carried combined genetic defects or a mutation, together with alphaFH. In the majority (87%), disease onset was preceeded by a triggering event; in 25% of cases diarrhea was the presenting symptom. More than 50% had normal serum C3 levels at presentation. Relapses were seen in half of the patients, and there was renal graft failure in all except one case following transplant. CONCLUSIONS: Performing adequate DNA analysis is essential for treatment and positive outcome in children with aHUS. The impact of intensive initial therapy and renal replacement therapy, as well as the high risk of recurrence of aHUS in renal transplant, warrants further understanding of the pathogenesis, which will lead to better treatment options.01 augustus 201
Global quieting of high-frequency seismic noise due to COVID-19 pandemic lockdown measures
Human activity causes vibrations that propagate into the ground as high-frequency seismic waves. Measures to mitigate the COVID-19 pandemic caused widespread changes in human activity, leading to a months-long reduction in seismic noise of up to 50%. The 2020 seismic noise quiet period is the longest and most prominent global anthropogenic seismic noise reduction on record. While the reduction is strongest at surface seismometers in populated areas, this seismic quiescence extends for many kilometers radially and hundreds of meters in depth. This provides an opportunity to detect subtle signals from subsurface seismic sources that would have been concealed in noisier times and to benchmark sources of anthropogenic noise. A strong correlation between seismic noise and independent measurements of human mobility suggests that seismology provides an absolute, real-time estimate of population dynamics
Consensus guidelines for the use and interpretation of angiogenesis assays
The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference