Lupus and Sjögren’s syndrome distinct disease endotypes clustered based on activity scores and immune profiles

Background: Sjögren’s syndrome (SS) is a chronic autoimmune disorder affecting approximately 0.1–0.4% of the general population with a female-to-male ratio of 9:1 usually diagnosed in the fourth and fifth decades of life [1]. Clinically, SS is typified by ocular and oral dryness developed as a consequence of the autoimmune process. It may occur either alone, as primary (p)SS, or secondary to other autoimmune disease, often rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or systemic sclerosis, secondary (s)SS. Objectives: 1) Identify the peripheral B and T cells abnormalities in patients with pSS, secondary SS associated with systemic lupus erythematosus (SLE) and SLE alone in comparison to healthy donors. 2) Correlate immune phenotypes with clinical features and serological parameters. 3) Identify distinct patients’ endotypes relevant for therapeutic strategies. Methods: Blood samples, clinical and laboratory parameters from 28 patients with pSS, 32 SLE, 15 SS/SLE and age/sex-matched HC were obtained. Immunophenotyping and lipid-raft analyses were performed by flow-cytometry. Results: There were distinct CD19+ B cells, and CD4+ and CD8+ T cell subpopulations observed in pSS, SLE and SS/SLE patients compared to healthy donors. SS/SLE have the most striking B cell phenotype abnormalities than patients with pSS or SLE (increased Bm2 cells and decreased early and late Bm5 cells).There were significant positive and negative correlations of immune cells with clinical parameters in pSS, SLE and SS/SLE patients. The fold-change of memory B cells was significantly reduced in all disease groups with comparison to healthy controls. Fold-change of CD8+ T responder cells were significantly reduced in all diseases, and similarly, CD4+ naïve T cells in SLE and SS/SLE. A highly significant increase in CD4+ T regulatory was observed in pSS. Hierarchical clustering of immune cells in patients yielded 5 distinct endotypes, with clustering reflected in patients with similar disease activity scores. Conclusions: This is the first comprehensive immunophenotype analysis performed patients with pSS, SLE and SS/SLE. We identified significant reduction in memory B cells fold-changed in all disease groups, reduction in CD4+ naïve T cells in SLE and SS/SLE and reduction in T responders in all disease CD8+ in comparison to healthy donors. The most significant T cell abnormalities were found in patients with SLE, however a significant correlation between lipid raft expression as marker of cell activation and disease activity score (ESSDAI) was found only in pSS patients. The five distinct disease endotype clustering showed distinct immune profile in patients with overlapping autoimmune conditions which is particularly relevant for stratification of therapy

Boundedness, compactness and Schatten-class membership of weighted composition operators

The boundedness and compactness of weighted composition operators on the Hardy space ${\mathcal H}^2$ of the unit disc is analysed. Particular reference is made to the case when the self-map of the disc is an inner function. Schatten-class membership is also considered; as a result, stronger forms of the two main results of a recent paper of Gunatillake are derived. Finally, weighted composition operators on weighted Bergman spaces $\mathcal{A}^2 \alpha(\mathbb{D})$ are considered, and the results of Harper and Smith, linking their properties to those of Carleson embeddings, are extended to this situation.Comment: 12 page

Hydrodynamic bubble coarsening in off-critical vapour-liquid phase separation

Late-stage coarsening in off-critical vapour-liquid phase separation is re-examined. In the limit of bubbles of vapour distributed throughout a continuous liquid phase, it is argued that coarsening proceeds via inertial hydrodynamic bubble collapse. This replaces the Lifshitz-Slyozov-Wagner mechanism seen in binary liquid mixtures. The arguments are strongly supported by simulations in two dimensions using a novel single-component soft sphere fluid.Comment: 5 pages, 3 figures, revtex3.

Excitations in the Halo Nucleus He-6 Following The Li-7(gamma,p)He-6 Reaction

A broad excited state was observed in 6-He with energy E_x = 5 +/- 1 MeV and width Gamma = 3 +/- 1 MeV, following the reaction Li-7(gamma,p)He-6. The state is consistent with a number of broad resonances predicted by recent cluster model calculations. The well-established reaction mechanism, combined with a simple and transparent analysis procedure confers considerable validity to this observation.Comment: 3 pages of LaTeX, 3 figures in PostScript, approved for publication in Phys. Rev. C, August, 200

Persistence exponents in a 3D symmetric binary fluid mixture

The persistence exponent, theta, is defined by N_F sim t^theta, where t is the time since the start of the coarsening process and the "no-flip fraction", N_F, is the number of points that have not seen a change of "color" since t=0. Here we investigate numerically the persistence exponent for a binary fluid system where the coarsening is dominated by hydrodynamic transport. We find that N_F follows a power law decay (as opposed to exponential) with the value of theta somewhat dependent on the domain growth rate (L sim t^alpha, where L is the average domain size), in the range theta=1.23 +-0.1 (alpha = 2/3) to theta=1.37 +-0.2 (alpha=1). These alpha values correspond to the inertial and viscous hydrodynamic regimes respectively.Comment: 9 pages RevTex, 9 figures included as eps files on last 3 pages, submitted to Phys Rev

The Period Changes of the Cepheid RT Aurigae

Observations of the light curve for the 3.7-day Cepheid RT Aur both before and since 1980 indicate that the variable is undergoing an overall period increase, amounting to +0.082 +-0.012 s/yr, rather than a period decrease, as implied by all observations prior to 1980. Superposed on the star's O-C variations is a sinusoidal trend that cannot be attributed to random fluctuations in pulsation period. Rather, it appears to arise from light travel time effects in a binary system. The derived orbital period for the system is P = 26,429 +-89 days (72.36 +-0.24 years). The inferred orbital parameters from the O-C residuals differ from those indicated by existing radial velocity data. The latter imply the most reasonable results, namely a1 sin i = 9.09 (+-1.81) x 10^8 km and a minimum secondary mass of M2 = 1.15 +-0.25 Msun. Continued monitoring of the brightness and radial velocity changes in the Cepheid are necessary to confirm the long-term trend and to provide data for a proper spectroscopic solution to the orbit.Comment: Accepted for publication in PASP (November 2007

3D Spinodal Decomposition in the Inertial Regime

We simulate late-stage coarsening of a 3D symmetric binary fluid using a lattice Boltzmann method. With reduced lengths and times l and t respectively (scales set by viscosity, density and surface tension) our data sets cover 1 < l 100 we find clear evidence of Furukawa's inertial scaling (l ~ t^{2/3}), although the crossover from the viscous regime (l ~ t) is very broad. Though it cannot be ruled out, we find no indication that Re is self-limiting (l ~ t^{1/2}) as proposed by M. Grant and K. R. Elder [Phys. Rev. Lett. 82, 14 (1999)].Comment: 4 pages, 3 eps figures, RevTex, minor changes to bring in line with published version. Mobility values added to Table

Spinodal decomposition of off-critical quenches with a viscous phase using dissipative particle dynamics in two and three spatial dimensions

We investigate the domain growth and phase separation of hydrodynamically-correct binary immiscible fluids of differing viscosity as a function of minority phase concentration in both two and three spatial dimensions using dissipative particle dynamics. We also examine the behavior of equal-viscosity fluids and compare our results to similar lattice-gas simulations in two dimensions.Comment: 34 pages (11 figures); accepted for publication in Phys. Rev.