A New Approach to Searching for Dark Matter Signals in Fermi-LAT Gamma Rays

Several cosmic ray experiments have measured excesses in electrons and positrons, relative to standard backgrounds, for energies from ~ 10 GeV - 1 TeV. These excesses could be due to new astrophysical sources, but an explanation in which the electrons and positrons are dark matter annihilation or decay products is also consistent. Fortunately, the Fermi-LAT diffuse gamma ray measurements can further test these models, since the electrons and positrons produce gamma rays in their interactions in the interstellar medium. Although the dark matter gamma ray signal consistent with the local electron and positron measurements should be quite large, as we review, there are substantial uncertainties in the modeling of diffuse backgrounds and, additionally, experimental uncertainties that make it difficult to claim a dark matter discovery. In this paper, we introduce an alternative method for understanding the diffuse gamma ray spectrum in which we take the intensity ratio in each energy bin of two different regions of the sky, thereby canceling common systematic uncertainties. For many spectra, this ratio fits well to a power law with a single break in energy. The two measured exponent indices are a robust discriminant between candidate models, and we demonstrate that dark matter annihilation scenarios can predict index values that require "extreme" parameters for background-only explanations.Comment: v1: 11 pages, 7 figures, 1 table, revtex4; v2: 13 pages, 8 figures, 1 table, revtex4, Figure 4 added, minor additions made to text, references added, conclusions unchanged, published versio

Speech Communication

Contains reports on four research projects.National Institutes of Health (Grant 5 RO1 NS04332-15)National Institutes of Health (Grant 5 T32 NS07040-03)National Institutes of Health (Grant 5 RO1 NS13028-02)National Science Foundation (Grant BNS76-80278

Promotion of Inflammatory Arthritis by Interferon Regulatory Factor 5 in a Mouse Model

OBJECTIVE: Polymorphisms in the transcription factor interferon regulatory factor 5 (IRF5) are associated with an increased risk of developing rheumatoid arthritis (RA). This study was undertaken to determine the role of IRF5 in a mouse model of arthritis development. METHODS: K/BxN serum-transfer arthritis was induced in mice deficient in IRF5, or lacking IRF5 only in myeloid cells, and arthritis severity was evaluated. K/BxN arthritis was also induced in mice deficient in TRIF, Toll-like receptor 2 (TLR2), TLR3, TLR4, and TLR7 to determine the pathways through which IRF5 might promote arthritis. In vitro studies were performed to determine the role of IRF5 in interleukin-1 (IL-1) receptor and TLR signaling. RESULTS: Arthritis severity was reduced in IRF5-deficient, TRIF-deficient, TLR3-deficient, and TLR7-deficient mice. The expression of multiple genes regulating neutrophil recruitment or function and bioactive IL-1beta formation was reduced in the joints during active arthritis in IRF5-deficient mice. In vitro studies showed that TLR7 and the TRIF-dependent TLR3 pathway induce proinflammatory cytokine production in disease-relevant cell types in an IRF5-dependent manner. CONCLUSION: Our findings indicate that IRF5 contributes to disease pathogenesis in inflammatory arthritis. This is likely due at least in part to the role of IRF5 in mediating proinflammatory cytokine production downstream of TLR7 and TLR3. Since TLR7 and TLR3 are both RNA-sensing TLRs, this suggests that endogenous RNA ligands present in the inflamed joint promote arthritis development. These findings may be relevant to human RA, since RNA capable of activating TLR7 and TLR3 is present in synovial fluid and TLR7 and TLR3 are up-regulated in the joints of RA patients