Universally Leptophilic Dark Matter From Non-Abelian Discrete Symmetry

The positron anomaly recently reported by the cosmic-ray measurements can be explained by the decaying dark matter scenario, where it decays mainly into leptons with the lifetime of O(10^26) second. When the dark matter is a fermionic particle, the lifetime of this order is known to be obtained by a dimension 6 operator suppressed by the unification scale 10^16 GeV, while such decay operators do not necessarily involve only leptons. In addition, the scenario would be spoiled if there exist lower-dimensional operators inducing the dark matter decay. We show in this letter that a single non-Abelian discrete symmetry such as A_4 is possible to prohibit all such harmful (non-leptonically coupled and lower-dimensional) operators. Moreover, the dark matter decays into charged leptons in a flavor-blind fashion due to the non-Abelian flavor symmetry, which results in perfect agreements not only with the PAMELA data but also with the latest Fermi-LAT data reported very recently. We also discuss some relevance between the discrete symmetry and neutrino physics.Comment: 13 pages, 2 tables, 1 figur

1998 Superoutburst of the Large-Amplitude SU UMa-Type Dwarf Nova WX Ceti

We observed the 1998 November superoutburst of WX Cet, a dwarf nova originally proposed as a WZ Sge-like system. The observation established that WX Cet is an SU UMa-type dwarf nova with a mean superhump period of 0.05949(1) d, which is 2.1% longer than the reported orbital period. The lack of early superhumps at the earliest stage of the superoutburst, the rapid development of usual superhumps, and the possible rapid decay of late superhumps seem to support that WX Cet is a fairly normal large-amplitude SU UMa-type dwarf nova, rather than a WZ Sge-type dwarf nova with a number of peculiarities. However, a period increase of superhumps at a rate dot(P)/P = (+8.5+/-1.0) x 10^-5 was observed, which is one of the largest dot(P)/P ever observed in SU UMa-type dwarf novae. A linear decline of light, with a rate of 0.10 mag/d, was observed in the post-superoutburst stage. This may be an exemplification of the decay of the viscosity in the accretion disk after the termination of a superoutburst, mechanism of which is proposed to explain a variety of post-superoutburst phenomena in some SU UMa-type dwarf novae.Comment: 8 pages, 8 figures, accepted for publication in Publ. Astron. Soc. Japa

Revisiting Aire and tissue-restricted antigens at single-cell resolution

The thymus is a highly specialized organ that plays an indispensable role in the establishment of self-tolerance, a process characterized by the “education” of developing T-cells. To provide competent T-cells tolerant to self-antigens, medullary thymic epithelial cells (mTECs) orchestrate negative selection by ectopically expressing a wide range of genes, including various tissue-restricted antigens (TRAs). Notably, recent advancements in the high-throughput single-cell analysis have revealed remarkable heterogeneity in mTECs, giving us important clues for dissecting the mechanisms underlying TRA expression. We overview how recent single-cell studies have furthered our understanding of mTECs, with a focus on the role of Aire in inducing mTEC heterogeneity to encompass TRAs

PHENOTYPIC ANALYSIS OF MICE DEFICIENT FOR Ly6C1/Ly6C2

Ly6C comprises two homologous components of Ly6C1 and Ly6C2, and the expression of either of the Ly6C molecules defines unique functional subsets of monocytes. Ly6C is also expressed by other immune cell types, including Aire-expressing medullary thymic epithelial cells. Because the role of Ly6C expression in determining the functional subsets remains unclear, we generated mice deficient for both Ly6C1 and Ly6C2 with CRISPR-Cas9–mediated deletion. Mice deficient for Ly6C1/Ly6C2 showed no major alterations in the subsets and function of monocyte and other immune cells, including the cells involved in the dextran sulfate sodium salt–induced colitis model. By generating the mice deficient for Ly6C1 alone, we have also investigated the expression pattern of Ly6C1 and Ly6C2 in immune cells. Except for medullary thymic epithelial cells and CD4 single-positive T cells, immune cells predominantly expressed Ly6C2. Thus, despite the importance as a marker with a unique differential expression pattern, the Ly6C molecules have no major impact on determining the functional subsets and maintaining immune homeostasis

Particle Swarm Optimization Combining Diversification and Intensification for Nonlinear Integer Programming Problems

In this research, focusing on nonlinear integer programming problems, we propose an approximate solution method based on particle swarm optimization proposed by Kennedy et al. And we developed a new particle swarm optimization method which is applicable to discrete optimization problems by incoporating a new method for generating initial search points, the rounding of values obtained by the move scheme and the revision of move methods. Furthermore, we showed the efficiency of the proposed particle swarm optimization method by comparing it with an existing method through the application of them into the numerical examples. Moreover we expanded revised particle swarm optimization method for application to nonlinear integer programming problems and showed more effeciency than genetic algorithm. However, variance of the solutions obtained by the PSO method is large and accuracy is not so high. Thus, we consider improvement of accuracy introducing diversification and intensification

Aire suppresses CTLA-4 expression from the thymic stroma to control autoimmunity

Impaired production of thymic regulatory T cells (Tregs) is implicated in the development of Aire-dependent autoimmunity. Because Tregs require agonistic T cell receptor stimuli by self-antigens to develop, reduced expression of self-antigens from medullary thymic epithelial cells (mTECs) has been considered to play a major role in the reduced Treg production in Aire deficiency. Here, we show that mTECs abnormally express co-inhibitory receptor CTLA-4 if Aire is non-functional. Upon binding with CD80/CD86 ligands expressed on thymic dendritic cells (DCs), the ectopically expressed CTLA-4 from Aire-deficient mTECs removes the CD80/CD86 ligands from the DCs. This attenuates the ability of DCs to provide co-stimulatory signals and to present self-antigens transferred from mTECs, both of which are required for Treg production. Accordingly, impaired production of Tregs and organ-specific autoimmunity in Aire-deficient mice are rescued by the depletion of CTLA-4 expression from mTECs. Our studies illuminate the significance of mTEC-DC interaction coordinated by Aire for the establishment of thymic tolerance

Amelioration of diabetes in NOD by additive Aire

Tissue-specific autoimmune diseases are assumed to arise through malfunction of two checkpoints for immune tolerance: defective elimination of autoreactive T cells in the thymus and activation of these T cells by corresponding autoantigens in the periphery. However, evidence for this model and the outcome of such alterations in each or both of the tolerance mechanisms have not been sufficiently investigated. We studied these issues by expressing human AIRE (huAIRE) as a modifier of tolerance function in NOD mice wherein the defects of thymic and peripheral tolerance together cause type I diabetes (T1D). Additive huAIRE expression in the thymic stroma had no major impact on the production of diabetogenic T cells in the thymus. In contrast, huAIRE expression in peripheral antigen-presenting cells (APCs) rendered the mice resistant to T1D, while maintaining other tissue-specific autoimmune responses and antibody production against an exogenous protein antigen, because of the loss of Xcr1+ dendritic cells, an essential component for activating diabetogenic T cells in the periphery. These results contrast with our recent demonstration that huAIRE expression in both the thymic stroma and peripheral APCs resulted in the paradoxical development of muscle-specific autoimmunity. Our results reveal that tissue-specific autoimmunity is differentially controlled by a combination of thymic function and peripheral tolerance, which can be manipulated by expression of huAIRE/Aire in each or both of the tolerance mechanisms