165 research outputs found

    IgG 3 + B cells are associated with the development of multiple sclerosis

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    Objectives Disease‐modifying therapies (DMTs) targeting B cells are amongst the most effective for preventing multiple sclerosis (MS) progression. IgG3 antibodies and their uncharacterised B‐cell clones are predicted to play a pathogenic role in MS. Identifying subsets of IgG3+ B cells involved in MS progression could improve diagnosis, could inform timely disease intervention and may lead to new DMTs that target B cells more specifically. Methods We designed a 31‐parameter B‐cell‐focused mass cytometry panel to interrogate the role of peripheral blood IgG3+ B cells in MS progression of two different patient cohorts: one to investigate the B‐cell subsets involved in conversion from clinically isolated syndrome (CIS) to MS; and another to compare MS patients with inactive or active stages of disease. Each independent cohort included a group of non‐MS controls. Results Nine distinct CD20+IgD−IgG3+ B‐cell subsets were identified. Significant changes in the proportion of CD21+CD24+CD27−CD38− and CD27+CD38hiCD71hi memory B‐cell subsets correlated with changes in serum IgG3 levels and time to conversion from CIS to MS. The same CD38− double‐negative B‐cell subset was significantly elevated in MS patients with active forms of the disease. A third CD21+CD24+CD27+CD38− subset was elevated in patients with active MS, whilst narrowband UVB significantly reduced the proportion of this switched‐memory B‐cell subset. Conclusion We have identified previously uncharacterised subsets of IgG3+ B cells and shown them to correlate with autoimmune attacks on the central nervous system (CNS). These results highlight the potential for therapies that specifically target IgG3+ B cells to impact MS progression

    Mineralogical characteristics influence the structure and pozzolanic reactivity of thermally and mechano-chemically activated meta-kaolinites

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    Increasing early age reactivity of cement replacements is a barrier to reducing the embodied carbon of blended Portland cements. Mechano-chemical activation is an emerging alternative to conventional thermal activation for clays, which can accelerate early age reactivity. Knowledge gaps on the structure and reactivity of mechano-chemically activated kaolinitic clays include the influence of Fe-bearing phases and the mineralogical characteristics of kaolinites from different sources. This study evaluated the effectiveness of mechano-chemical vs. thermal activation for an Fe-rich clay containing disordered kaolinite and 24 wt% goethite, and a low-Fe clay containing highly ordered kaolinite. In the Fe-rich clay, mechano-chemical activation simultaneously caused dehydroxylation of kaolinite to form meta-kaolinite, and dehydration of goethite to form hematite. Agglomerates of intermixed meta-kaolinite and goethite/hematite nanoparticles were shown to have similar Al and Si environments after thermal or mechano-chemical activation (as determined by STEM-EDX, 27Al and 29Si MAS nuclear magnetic resonance and electron energy loss spectroscopy). Mechano-chemical activation enhanced early age (<12 hours) reactivity for both clays. Evaluating early age reactivity by unit mass of anhydrous meta-kaolinite explains how surface-adsorbed moisture results in underperformance of mechano-chemical activation at later ageing times. External surface area alone does not predict reactivity acceleration well – edge : basal surface area of meta-kaolinite is proposed as a more relevant factor that governs early age performance of mechano-chemically activated clays. The structure–property–performance relations of mechano-chemically activated meta-kaolinites are explained through interactions of kaolinites' intrinsic mineralogical characteristics (i.e. initial particle size, aspect ratio, structural order) and extrinsic processing effects (i.e. intensive milling on structural order and physical characteristics)

    The remarkable outburst of the highly-evolved post period-minimum dwarf nova SSS J122221.7−311525

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    We report extensive 3-yr multiwavelength observations of the WZ Sge-type dwarf nova SSS J122221.7−311525 during its unusual double superoutburst, the following decline and in quiescence. The second segment of the superoutburst had a long duration of 33 d and a very gentle decline with a rate of 0.02 mag d−1, and it displayed an extended post-outburst decline lasting at least 500 d. Simultaneously with the start of the rapid fading from the superoutburst plateau, the system showed the appearance of a strong near-infrared excess resulting in very red colours, which reached extreme values (B − I ≃ 1.4) about 20 d later. The colours then became bluer again, but it took at least 250 d to acquire a stable level. Superhumps were clearly visible in the light curve from our very first time-resolved observations until at least 420 d after the rapid fading from the superoutburst. The spectroscopic and photometric data revealed an orbital period of 109.80 min and a fractional superhump period excess â‰Č0.8 per cent, indicating a very low mass ratio q â‰Č 0.045. With such a small mass ratio the donor mass should be below the hydrogen-burning minimum mass limit. The observed infrared flux in quiescence is indeed much lower than is expected from a cataclysmic variable with a near-main-sequence donor star. This strongly suggests a brown-dwarf-like nature for the donor and that SSS J122221.7−311525 has already evolved away from the period minimum towards longer periods, with the donor now extremely dim

    Cluster mutation-periodic quivers and associated Laurent sequences

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    We consider quivers/skew-symmetric matrices under the action of mutation (in the cluster algebra sense). We classify those which are isomorphic to their own mutation via a cycle permuting all the vertices, and give families of quivers which have higher periodicity. The periodicity means that sequences given by recurrence relations arise in a natural way from the associated cluster algebras. We present a number of interesting new families of non-linear recurrences, necessarily with the Laurent property, of both the real line and the plane, containing integrable maps as special cases. In particular, we show that some of these recurrences can be linearised and, with certain initial conditions, give integer sequences which contain all solutions of some particular Pell equations. We extend our construction to include recurrences with parameters, giving an explanation of some observations made by Gale. Finally, we point out a connection between quivers which arise in our classification and those arising in the context of quiver gauge theories.Comment: The final publication is available at www.springerlink.com. 42 pages, 35 figure
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