525 research outputs found

    Improved Semiclassical Approximation for Bose-Einstein Condensates: Application to a BEC in an Optical Potential

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    We present semiclassical descriptions of Bose-Einstein condensates for configurations with spatial symmetry, e.g., cylindrical symmetry, and without any symmetry. The description of the cylindrical case is quasi-one-dimensional (Q1D), in the sense that one only needs to solve an effective 1D nonlinear Schrodinger equation, but the solution incorporates correct 3D aspects of the problem. The solution in classically allowed regions is matched onto that in classically forbidden regions by a connection formula that properly accounts for the nonlinear mean-field interaction. Special cases for vortex solutions are treated too. Comparisons of the Q1D solution with full 3D and Thomas-Fermi ones are presented.Comment: 14 pages, 5 figure

    Existence and Uniqueness of Tri-tronqu\'ee Solutions of the second Painlev\'e hierarchy

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    The first five classical Painlev\'e equations are known to have solutions described by divergent asymptotic power series near infinity. Here we prove that such solutions also exist for the infinite hierarchy of equations associated with the second Painlev\'e equation. Moreover we prove that these are unique in certain sectors near infinity.Comment: 13 pages, Late

    Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response

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    © 2019, The Author(s). Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α 4 β 7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches

    Listeners form average-based representations of individual voice identities.

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    Models of voice perception propose that identities are encoded relative to an abstracted average or prototype. While there is some evidence for norm-based coding when learning to discriminate different voices, little is known about how the representation of an individual's voice identity is formed through variable exposure to that voice. In two experiments, we show evidence that participants form abstracted representations of individual voice identities based on averages, despite having never been exposed to these averages during learning. We created 3 perceptually distinct voice identities, fully controlling their within-person variability. Listeners first learned to recognise these identities based on ring-shaped distributions located around the perimeter of within-person voice spaces - crucially, these distributions were missing their centres. At test, listeners' accuracy for old/new judgements was higher for stimuli located on an untrained distribution nested around the centre of each ring-shaped distribution compared to stimuli on the trained ring-shaped distribution

    A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage

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    Background & Aims: C-C motif chemokine ligand 24 (CCL24) is a chemokine that regulates inflammatory and fibrotic activities through its receptor, C-C motif chemokine receptor (CCR3). The aim of the study was to evaluate the involvement of the CCL24-CCR3 axis in liver fibrosis and inflammation and to assess the potential of its blockade, by a monoclonal anti-CCL24 antibody, as a therapeutic strategy for non-alcoholic steatohepatitis (NASH) and liver fibrosis. Methods: Expression of CCL24 and CCR3 was evaluated in liver biopsies and blood samples. CCL24 involvement in NAFLD/NASH pathogenesis was assessed in Ccl24 knockout mouse using the methionine-choline deficient (MCD) diet experimental model. Antifibrotic and anti-inflammatory effects of CM-101 were tested in the MCD and STAM mouse models and in the thioacetamide (TAA) model in rats. Liver enzymes, liver morphology, histology and collagen deposition, as well as fibrosis- and inflammation-related protein expression were assessed. Activation of hepatic stellate cells (HSCs) was evaluated in the human LX2 cell line. Results: Patients with NASH and advanced NAFLD exhibited significant expression of both CCL24 and CCR3 in liver and blood samples. In the experimental MCD-diet model, Ccl24 knockout mice showed an attenuated liver damage response compared to wild-type mice, exhibiting reduced histological NAFLD activity scores and fibrosis, as well as lower levels of liver enzymes. Blocking CCL24 using CM-101 robustly reduced liver damage in 3 experimental animal models (MCD, STAM and TAA), as demonstrated by attenuation of liver fibrosis and NAFLD activity score. Furthermore, blocking CCL24 by CM-101 significantly inhibited CCL24-induced HSC motility, α-SMA expression and pro-collagen I secretion. Conclusion: Our results reveal that blocking CCL24 significantly attenuates liver fibrosis and inflammation and may have a potential therapeutic effect in patients with NASH and/or liver fibrosis. Lay summary: CCL24 is a chemokine that regulates inflammation and fibrosis. It was found to be significantly expressed in patients with non-alcoholic steatohepatitis, in whom it regulates profibrotic processes in the liver. Herein, we show that blockade of CCL24 using a monoclonal antibody robustly attenuated liver fibrosis and inflammation in animal models, thus suggesting a potential therapeutic role for an anti-CCL24 agent

    Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease.

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    Long noncoding RNAs (lncRNA) are key regulators of gene transcription and many show tissue-specific expression. We previously defined a novel inflammatory and metabolic ileal gene signature in treatment-naive pediatric Crohn disease (CD). We now extend our analyses to include potential regulatory lncRNA.Using RNAseq, we systematically profiled lncRNAs and protein-coding gene expression in 177 ileal biopsies. Co-expression analysis was used to identify functions and tissue-specific expression. RNA in situ hybridization was used to validate expression. Real-time polymerase chain reaction was used to test lncRNA regulation by IL-1β in Caco-2 enterocytes.We characterize widespread dysregulation of 459 lncRNAs in the ileum of CD patients. Using only the lncRNA in discovery and independent validation cohorts showed patient classification as accurate as the protein-coding genes, linking lncRNA to CD pathogenesis. Co-expression and functional annotation enrichment analyses across several tissues and cell types 1showed that the upregulated LINC01272 is associated with a myeloid pro-inflammatory signature, whereas the downregulated HNF4A-AS1 exhibits association with an epithelial metabolic signature. We confirmed tissue-specific expression in biopsies using in situ hybridization, and validated regulation of prioritized lncRNA upon IL-1β exposure in differentiated Caco-2 cells. Finally, we identified significant correlations between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury.We systematically define differentially expressed lncRNA in the ileum of newly diagnosed pediatric CD. We show lncRNA utility to correctly classify disease or healthy states and demonstrate their regulation in response to an inflammatory signal. These lncRNAs, after mechanistic exploration, may serve as potential new tissue-specific targets for RNA-based interventions

    Utility of neutrophil Fcgamma receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn\u27s disease

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    BACKGROUND: Neutrophil expression of the Fcgamma receptor I (CD64) is upregulated in adult patients with clinically active inflammatory bowel disease (IBD). We tested the relationship of CD64 with mucosal inflammation and clinical relapse in pediatric Crohn\u27s disease (CD). METHODS: In a cohort of 208 newly diagnosed CD and 43 non-IBD controls, ileal expression of FcgammaRI/S100A9 was determined by RNA sequencing from biopsies obtained at ileocolonoscopy. In a second cohort, we tested for the peripheral blood polymorphonuclear neutrophil (PMN) CD64 index from 26 newly diagnosed CD, 30 non-IBD controls, and 83 children with established CD. RESULTS: Ileal FcgammaRIA mRNA expression was significantly elevated in CD at diagnosis compared with non-IBD controls (P \u3c 0.001), and correlated with ileal S100A9 (calprotectin) expression (r = 0.83, P \u3c 0.001). The median (range) PMN CD64 index for newly diagnosed CD was 2.3 (0.74-9.3) compared with 0.76 (0.39-1.2) for non-IBD controls (P \u3c 0.001) with 96% sensitivity and 90% specificity at the cut point of 1.0. The PMN CD64 index significantly correlated with mucosal injury as measured by the simple endoscopic score for CD (r = 0.62, P \u3c 0.001). Patients with CD in clinical remission receiving maintenance therapy with a PMN CD64 index1.0 (P \u3c 0.01). CONCLUSIONS: An elevated PMN CD64 index is associated with both mucosal inflammation and an increased risk for clinical relapse in pediatric CD. The PMN CD64 index is a reliable marker for sustained remission in patients with CD receiving maintenance therapy

    Quasi-linear Stokes phenomenon for the Painlev\'e first equation

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    Using the Riemann-Hilbert approach, the Ψ\Psi-function corresponding to the solution of the first Painleve equation, yxx=6y2+xy_{xx}=6y^2+x, with the asymptotic behavior y∼±−x/6y\sim\pm\sqrt{-x/6} as ∣x∣→∞|x|\to\infty is constructed. The exponentially small jump in the dominant solution and the coefficient asymptotics in the power-like expansion to the latter are found.Comment: version accepted for publicatio
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