25 research outputs found

    Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome

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    Inflammasomes are important for host defence against pathogens and homeostasis with commensal microbes. Here, we show non-haemolytic enterotoxin (NHE) from the neglected human foodborne pathogen Bacillus cereus is an activator of the NLRP3 inflammasome and pyroptosis. NHE is a non-redundant toxin to haemolysin BL (HBL) despite having a similar mechanism of action. Via a putative transmembrane region, subunit C of NHE initiates binding to the plasma membrane, leading to the recruitment of subunit B and subunit A, thus forming a tripartite lytic pore that is permissive to efflux of potassium. NHE mediates killing of cells from multiple lineages and hosts, highlighting a versatile functional repertoire in different host species. These data indicate that NHE and HBL operate synergistically to induce inflammation and show that multiple virulence factors from the same pathogen with conserved function and mechanism of action can be exploited for sensing by a single inflammasome

    Identifying cancer-associated leukocyte profiles using high-resolution flow cytometry screening and machine learning

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    BackgroundMachine learning (ML) is a valuable tool with the potential to aid clinical decision making. Adoption of ML to this end requires data that reliably correlates with the clinical outcome of interest; the advantage of ML is that it can model these correlations from complex multiparameter data sets that can be difficult to interpret conventionally. While currently available clinical data can be used in ML for this purpose, there exists the potential to discover new “biomarkers” that will enhance the effectiveness of ML in clinical decision making. Since the interaction of the immune system and cancer is a hallmark of tumor establishment and progression, one potential area for cancer biomarker discovery is through the investigation of cancer-related immune cell signatures. Hence, we hypothesize that blood immune cell signatures can act as a biomarker for cancer progression.MethodsTo probe this, we have developed and tested a multiparameter cell-surface marker screening pipeline, using flow cytometry to obtain high-resolution systemic leukocyte population profiles that correlate with detection and characterization of several cancers in murine syngeneic tumor models.ResultsWe discovered a signature of several blood leukocyte subsets, the most notable of which were monocyte subsets, that could be used to train CATboost ML models to predict the presence and type of cancer present in the animals.ConclusionsOur findings highlight the potential utility of a screening approach to identify robust leukocyte biomarkers for cancer detection and characterization. This pipeline can easily be adapted to screen for cancer specific leukocyte markers from the blood of cancer patient

    Feature combination and relevance feedback for 3D model retrieval

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    10.1109/MMMC.2005.39Proceedings of the 11th International Multimedia Modelling Conference, MMM 2005334-33

    Polygonizing non-uniformly distributed 3D points by advancing mesh frontiers

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    Proceedings of Computer Graphics International Conference, CGI175-18

    Predator-Miner: Ad hoc mining of associations rules within a database management system

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    Proceedings - International Conference on Data Engineering327-328PIDE

    Splice variants of the mouse Tec gene are differentially expressed in vivo

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    Tec is a cytoplasmic protein tyrosine kinase that participates in the signalling pathways of a broad range of cytokines. Up to five different Tec isoforms have been reported in the literature. We report here the genomic organisation of the mouse Tec gene and the tissue expression pattern of the two predominant transcripts, TecIII and TecIV. The mouse Tec gene consists of 18 exons, spans more than 86 kb, and is 2.6 kb 5' to the gene for Txk, a Tec family member. Comparison of mouse and human Btk, human TXK, and mouse Tec genomic structures shows a high level of conservation of exon/intron boundaries. Compared with TecIV, the TecIII transcript has a 66-bp deletion in the SH3 domain encoding region and is revealed here to arise by alternative splicing of exon 8. We show that both TecIII and TecIV are expressed as early as embryonic day 10.5 in mouse development, as well as in adult and embryonic organs. The ratio of TecIV to TecIII expression is markedly reduced in adult liver and kidney tissues and d16 embryonic limb

    3D model retrieval with morphing-based geometric and topological feature maps

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    Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition2II/656-II/661PIVR
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