4,370 research outputs found

    Role of macrophage metalloelastase in gut inflammation. [Issue: Inflammatory Bowel Disease: Genetics, Barrier Function, Immunologic Mechanisms and Microbial]

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    Matrix metalloproteinases (MMPs) are involved in a number of physiological and pathologic processes including the inflammation found in IBD. We have shown that MMP-3 is upregulated in Crohn's disease and in ulcerative colitis. This study shows a potential role for MMP-12 in these idiopathic diseases

    Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases

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    BACKGROUND & AIMS: Activation of lamina propria T cells with pokeweed mitogen in human fetal gut explant cultures results in severe mucosal injury. In the same system, Staphylococcus aureus enterotoxin B produces villus atrophy and crypt cell hyperplasia. The aim of this study was to examine the ability of interleukin (IL)-10 to modify these changes. METHODS: Mucosal pathology and lamina propria glycosaminoglycans were assessed histologically, and CD3(+), CD25(+) and alpha-actin smooth muscle-positive cells were determined by immunohistochemistry. Reverse plaque assays and quantitative reverse-transcriptase polymerase chain reaction were used to analyze the cytokine response. Matrix metalloproteinase production was analyzed by Western blotting, in situ hybridization, and zymography. RESULTS: Both experimental enteropathies produced mucosal damage, although injury was greater after pokeweed mitogen activation than S. aureus enterotoxin B. In both cases, the increase in cytokine-secreting cells and transcripts observed after T-cell activation was inhibited by IL-10. IL-10 also inhibited the increase in collagenase and stromelysin-1 in the explant culture supernatants and the loss of glycosaminoglycans. IL-10 decreased metalloproteinase production in control explants and increased matrix. In mesenchymal cells, IL-10 had a minor effect on metalloproteinase production. CONCLUSIONS: IL-10 down-regulates mucosal T-cell activation, metalloproteinase production, and loss of extracellular matrix and prevents mucosal damage in the gut

    Matrix metalloproteinase-3 production by gut IgG plasma cells in chronic inflammatory bowel disease.

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    Background: In both ulcerative colitis (UC) and Crohn's disease (CD) there is a marked increase in mucosal IgG plasma cells (PC), although their precise role is not well established. In this study we isolated gut PCs from patients with IBD and normal controls and analyzed cytokine production, matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 production, and PC longevity ex vivo.Methods: Lamina propria mononuclear cells (LPMCs) were isolated from patients with CD (n = 19), UC (n = 27), and normal controls (n = 42). PCs were further selected by immunomagnetic isolation using CD138 microbeads. Cytokine, MMP-3, and TIMP-1 expression was investigated by Taqman polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and confocal microscopy. PC lifespan in vitro was studied by ELISpot analysis.Results: PCs from both controls and IBD patients contained high levels of transcripts for TGFbeta, whereas they did not contain significant transcripts for IL-4, IL-5, IL-10, IFNgamma, TNF, or IL-12p40. PCs from patients with CD and UC expressed significantly higher levels of MMP-3 protein and transcripts than controls (P < 0.0001). The vast majority of MMP-3-expressing PCs were IgG+ve. In culture, IgA PCs from both IBD patients and controls persisted for only a few days, but IgG PCs from IBD patients persisted for at least 3 weeks.Conclusions: We have demonstrated that IgG PCs from patients with IBD express large amounts of MMP-3 and that they appear to be long-lived. These results identify a new pathway by which IgG PCs may damage the gut.(Inflamm Bowel Dis 2007)

    CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

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    The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-valu

    Quantum SL(2,R)SL(2,\mathbb{R}) and its irreducible representations

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    We define for real qq a unital *-algebra Uq(sl(2,R))U_q(\mathfrak{sl}(2,\mathbb{R})) quantizing the universal enveloping *-algebra of sl(2,R)\mathfrak{sl}(2,\mathbb{R}). The *-algebra Uq(sl(2,R))U_q(\mathfrak{sl}(2,\mathbb{R})) is realized as a *-subalgebra of the Drinfeld double of Uq(su(2))U_q(\mathfrak{su}(2)) and its dual Hopf *-algebra Oq(SU(2))\mathcal{O}_q(SU(2)), generated by the equatorial Podle\'s sphere coideal *-subalgebra Oq(K\SU(2))\mathcal{O}_q(K\backslash SU(2)) of Oq(SU(2))\mathcal{O}_q(SU(2)) and its associated orthogonal coideal *-subalgebra Uq(k)Uq(su(2))U_q(\mathfrak{k}) \subseteq U_q(\mathfrak{su}(2)). We then classify all the irreducible *-representations of Uq(sl(2,R))U_q(\mathfrak{sl}(2,\mathbb{R})).Comment: 22 pages; author accepted manuscrip

    On the sheaf-theoretic SL(2, C) Casson–Lin invariant

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    We prove that the (τ-weighted, sheaf-theoretic) SL(2, C) Casson–Lin invariant introduced by Manolescu and the first author is generically independent of the parameter τ and additive under connected sums of knots in integral homology 3-spheres. This addresses two questions asked by Manolescu and the first author. Our arguments involve a mix of topology and algebraic geometry, and rely crucially on the fact that the SL(2, C) Casson–Lin invariant admits an alternative interpretation via the theory of Behrend functions.</p

    Candidatus Rhetoricae (or Novus Candidatus).

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    This little book is a find whatever it finally turns out to be! For now it seems to be a Jesuit collegium text in rhetoric following the Progymnasmata of Aphthonius. If one works from the back of the book, there is an apparently independent 48-page work, Angelus Pacis by Nicolas Caussini (Latinized name), S.J. The rest of the book seems to be a commentary on or presentation of Aphthonius' Progymnasmata in 3 parts covering 435 pages, followed by a T of C and an AI, which is often one page off. Pars II is titled Rhetoricae Praecepta, Pars III De Panegyrico seu Laudatione. Pars I seems to be Apparatus ad Fabulam et Narrationem. Fable is handled on 15-31. After the famous Greek definition of Theion done into Latin ( sermo falsus veritatem effingens ), the author distinguishes rational (human) and moral (animal) fables, with mixed fables including both. He holds (19) that the sense of the fable generally needs to be expressed; otherwise people often miss the point of a fable. His Latin for promythium is praefabulatio, for epimythium affabulatio. Apologus and parabola are identical for him with fabula. After describing the qualities and uses of fables, the author presents some nine fables that exemplify various levels of style, twice telling the same stories on two levels (WL and FC). The last example is of the florid style: The Silkworm and the Spider takes four pages to tell! I found this book sitting in a box of disparate, unmarked, old books. It pays to look!This is a hardbound book (hard cover)Language note: Bilingual: Greek/LatinElzevers

    Searches for New Physics effects in b →sl-sl+ transitions

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    The dissertation aims at presenting the current situation in the measurements of electroweak penguin diagrams dominated decays: b → sl−l+1 . These decays have been a smoking gun for hunting for New Physics effects over many years, but in the last three years the research on these phenomena has intensified due to new measurements. Enormous progress has been made both on the theoretical and the experimental sides to understand the measured deviations from the current Standard Model predictions, referred to in what follows as “anomalies”. The author of this dissertation has been one of the main authors of the angular analysis of B0→ K∗ 0µ+µ− decay in the LHCb experiment, which has been widely regarded as one of the most important results of the flavour physics sector in recent years. He has proposed a method called “the method of moments” to measure the angular terms of this decay, which he has later successfully applied in the measurement itself. Moreover, he has been the driving force behind the two other important analyses in LHCb: the measurement of the angular distribution and branching ratio of the B0→ K∗ 0 (1430)µ+µ− decay, where again the method of moments has been used to obtain the angular coefficients, and the search for the light scalar particle that can be produced in the b → s transitions and that decays to a dimuon pair. In this case no signal has been observed and the upper limits on the branching fraction have been set, later to be used for constraining the inflaton model. The dissertation is organized as follows: the brief introduction is followed by, the second chapter devoted to a theoretical description of rare B decays, where the effective field theory formalism is introduced. Furthermore, the author discusses the current theoretical problems in calculating the Standard Model predictions for the b → sl−l+ processes. Last but not least, the optimised angular observables that are less dependent on the form factors uncertainness are derived. The third chapter describes the experimental apparatus used in the b → sl−l+ measurements. Special focus is put on the sub-detectors that play an important role in the studies of b → sl−l+ transitions. Chapters 4, 5, 6 are devoted to describing the data analyses performed by the author in the LHCb experiment. In Chapter 7 the global analysis of electroweak penguin decays is presented. This kind of global analysis has become extremely popular in the past few years as it helps to constrain and pin down those New Physics models that are likely to be responsible for the observed anomalies. The author of this monograph is involved in one of the biggest collaborations performing New Physics fits, where he is the convenor of the Flavour Working group. Furthermore, the author presents his own study on separating the long distance effects in the B0→ K∗ 0µ+µ−decay. This is the state of the art way of determining those contributions. The chapter ends with a description of possible New Physics models that can explain the observed discrepancies

    SL(n)\operatorname{SL}(n) contravariant function-valued valuations on polytopes

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    We present a complete classification of SL(n)\operatorname{SL}(n) contravariant, C(Rn{o})C(\mathbb{R}^n\setminus\{o\})-valued valuations on polytopes, without any additional assumptions.It extends the previous results of the second author [Int. Math. Res. Not. 2020] which have a good connection with the LpL_p and Orlicz Brunn-Minkowski theory. Additionally, our results deduce a complete classification of SL(n)\operatorname{SL}(n) contravariant symmetric-tensor-valued valuations on polytopes

    The Laurent Extension of Quantum Plane: a Complete List of Uq(sl₂)-Symmetries

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    This work finishes a classification of Uq(sl₂)-symmetries on the Laurent extension Cq[x±¹,y±¹] of the quantum plane. After reproducing the partial results of a previous paper of the author related to symmetries with non-trivial action of the Cartan generator(s) of Uq(sl₂) and the generic symmetries, a complete collection of non-generic symmetries is presented. Together, these collections constitute a complete list of Uq(sl₂)-symmetries on Cq[x±¹,y±¹].The author would like to thank the anonymous referees for a large number of comments and suggestions that substantially improved the initial version of this paper
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