The Abundance and Structure of Subhaloes near the Free Streaming Scale and Their Impact on Indirect Dark Matter Searches

The free streaming motion of dark matter particles imprints a cutoff in the matter power spectrum and set the scale of the smallest dark matter halo. Recent cosmological $N$-body simulations have shown that the central density cusp is much steeper in haloes near the free streaming scale than in more massive haloes. Here, we study the abundance and structure of subhaloes near the free streaming scale at very high redshift using a suite of unprecedentedly large cosmological $N$-body simulations, over a wide range of the host halo mass. The subhalo abundance is suppressed strongly below the free streaming scale, but the ratio between the subhalo mass function in the cutoff and no cutoff simulations is well fitted by a single correction function regardless of the host halo mass and the redshift. In subhaloes, the central slopes are considerably shallower than in field haloes, however, are still steeper than that of the NFW profile. Contrary, the concentrations are significantly larger in subhaloes than haloes and depend on the subhalo mass. We compare two methods to extrapolate the mass-concentration relation of haloes and subhaloes to z=0 and provide a new simple fitting function for subhaloes, based on a suite of large cosmological $N$-body simulations. Finally, we estimate the annihilation boost factor of a Milky-Way sized halo to be between 1.8 and 6.2.Comment: 11 pages, 9 figures, accepted by MNRA

Halo Substructure Boosts to the Signatures of Dark Matter Annihilation

The presence of dark matter substructure will boost the signatures of dark matter annihilation. We review recent progress on estimates of this subhalo boost factor---a ratio of the luminosity from annihilation in the subhalos to that originating the smooth component---based on both numerical $N$-body simulations and semi-analytic modelings. Since subhalos of all the scales, ranging from the Earth mass (as expected, e.g., the supersymmetric neutralino, a prime candidate for cold dark matter) to galaxies or larger, give substantial contribution to the annihilation rate, it is essential to understand subhalo properties over a large dynamic range of more than twenty orders of magnitude in masses. Even though numerical simulations give the most accurate assessment in resolved regimes, extrapolating the subhalo properties down in sub-grid scales comes with great uncertainties---a straightforward extrapolation yields a very large amount of the subhalo boost factor of $\gtrsim$100 for galaxy-size halos. Physically motivated theoretical models based on analytic prescriptions such as the extended Press-Schechter formalism and tidal stripping modeling, which are well tested against the simulation results, predict a more modest boost of order unity for the galaxy-size halos. Giving an accurate assessment of the boost factor is essential for indirect dark matter searches and thus, having models calibrated at large ranges of host masses and redshifts, is strongly urged upon.Comment: 30 pages, 5 figures; invited review published in Galaxies, special issue "The Role of Halo Substructure in Gamma-Ray Dark Matter Searches

Modeling evolution of dark matter substructure and annihilation boost

We study evolution of dark matter substructures, especially how they lose the mass and change density profile after they fall in gravitational potential of larger host halos. We develop an analytical prescription that models the subhalo mass evolution and calibrate it to results of N-body numerical simulations of various scales from very small (Earth size) to large (galaxies to clusters) halos. We then combine the results with halo accretion histories, and calculate the subhalo mass function that is physically motivated down to Earth-mass scales. Our results --- valid for arbitrary host masses and redshifts --- show reasonable agreement with those of numerical simulations at resolved scales. Our analytical model also enables self-consistent calculations of the boost factor of dark matter annhilation, which we find to increase from tens of percent at the smallest (Earth) and intermediate (dwarfs) masses to a factor of several at galaxy size, and to become as large as a factor of $\sim$10 for the largest halos (clusters) at small redshifts. Our analytical approach can accommodate substructures in the subhalos (sub-subhalos) in a consistent framework, which we find to give up to a factor of a few enhancement to the annihilation boost. Presence of the subhalos enhances the intensity of the isotropic gamma-ray background by a factor of a few, and as the result, the measurement by Fermi Large Area Telescope excludes the annihilation cross section greater than $\sim$$4\times 10^{-26}$ cm$^3$ s$^{-1}$ for dark matter masses up to $\sim$200 GeV.Comment: 14 pages, 9 figures, to appear in PR

マスト細胞とそのStat5活性のアレルギー性皮膚炎症における重要性

学位の種別: 論文博士審査委員会委員 : （主査）東京大学教授 水口 雅, 東京大学教授 上別府 圭子, 東京大学准教授 高橋 尚人, 東京大学講師 浦野 友彦, 東京大学講師 永松 健University of Tokyo(東京大学

Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion In Vitro

<p>Abstract</p> <p>Background</p> <p>MAdCAM-1 plays a central role in T-lymphocyte homing to the gut, but its role in chronic liver inflammation remains unknown. Therefore, this study measured MAdCAM-1 expression, regulation, and function in cultured murine hepatic endothelial cells.</p> <p>Methods</p> <p>Cultures of hepatic endothelial cells (HEC) were prepared from mice expressing a temperature-sensitive SV40 large T antigen (<it>H-2K</it>^<it>b</it>-<it>tsA58</it>) under the control of an IFN-γ promoter. Time and dose dependent expression of MAdCAM-1 in response to TNF-α, IL-1β and IFN-γ was studied by immunoblotting. Lymphocyte adhesion was studied using α₄β₇integrin expressing lymphocytes (TK-1) +/- anti-MAdCAM-1 mAb.</p> <p>Results</p> <p>TNF-α induced MAdCAM-1 dose-and time-dependently with maximum expression at 20 ng/ml and at 48 hours. IL-1β also induced MAdCAM-1 to a lesser extent compared to TNF-α; IFN-γ did not induce MAdCAM-1. TNF-α significantly increased lymphocyte-endothelial adhesion (<it>P </it>< 0.01), which was reversed by anti-MAdCAM-1 antibody. MAdCAM-1 expression was also reduced by N-acetylcysteine and by two NO donors (SperNO, DETANO) suggesting that hepatic endothelial MAdCAM-1 is oxidant and NO regulated.</p> <p>Conclusion</p> <p>MAdCAM-1 is a major determinant of leukocyte recruitment in chronic inflammation and is expressed by HEC in response to IL-1β and TNF-α. This system may provide a useful model for studying inflammatory mechanisms in liver disease and help determine if controlled MAdCAM-1 expression might influence inflammation in liver disease.</p

Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector

Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation

Phospholipase C-β3 Regulates FcɛRI-Mediated Mast Cell Activation by Recruiting the Protein Phosphatase SHP-1

SummaryMast cells are major effectors in high-affinity IgE receptor (FcɛRI)-dependent allergic reactions. Here we show that phospholipase C (PLC)-β3 is crucial for FcɛRI-mediated mast cell activation. Plcb3−/− mice showed blunted FcɛRI-dependent late-phase, but not acute, anaphylactic responses and airway inflammation. Accordingly, FcɛRI stimulation of Plcb3−/− mast cells exhibited reduced cytokine production but normal degranulation. Reduced cytokine production in Plcb3−/− cells could be accounted for by increased activity of the negative regulatory Src family kinase Lyn and reduced activities of the positive regulatory protein kinases MAPKs. Mechanistically, PLC-β3 constitutively interacts with FcɛRI, Lyn, and SHP-1 (protein phosphatase). SHP-1 probably recognizes its substrates Lyn and MAPKs via the recently described kinase tyrosine-based inhibitory motif, KTIM. Consistent with PLC-β3- and SHP-1-mediated repression of Lyn activity by dephosphorylation at Tyr396, FcɛRI-mediated phenotypes were similar in Plcb3−/− and SHP-1 mutant mast cells. Thus, we have defined a PLC-β3- and SHP-1-mediated signaling pathway for FcɛRI-mediated cytokine production

Embedded DRAM using c-axis-aligned crystalline In-Ga-Zn oxide FET with 1.8V-power-supply voltage

An embedded memory using c-axis aligned crystalline In-Ga-Zn oxide (CAAC-IGZO) FETs with an extremely low off-state current on the order of yoctoamperes (yA) (yocto- is a metric prefix denoting a factor of 10-24) is known as a potential next-generation memory [1][2]. A dynamic oxide semiconductor RAM (DOSRAM), where each memory cell is composed of one CAAC-IGZO FET and one capacitor, enables long data retention and long interval of refresh operations with an advantage of extremely low off-state current of the CAAC-IGZO FET. However, negative backgate voltage (Vbg) and word-line driving voltages of 0/3.3 V (VSSL/VDDH) had been required for an access transistor of the memory cell to satisfy high on-state current and low off-state current. This work shows that DOSRAM operates with 1.8 V-power supply voltage by using a novel driving method. Figure 1 shows Vg-Id performance of a CAAC-IGZO FET used as a cell transistor. The threshold voltage (Vth) of the CAAC-IGZO FET is controlled by changing a level of Vbg, whereas Vth of the Si FET is controlled by channel doping. Figure 2 shows a block diagram of a prototyped DOSRAM. The refresh rate in DOSRAM mainly depends on the leakage current of cell transistors. To reduce the refresh rate to once an hour, the off-state current of the cell transistors on a non-selected word line needs to be reduced to 200 zeptoamperes (zA) per FET (zepto- is a metric prefix denoting a factor of 10-21) or lower at 85C. The required Vbg is -7.0 V to achieve such an off-state current at Vg 0 V, for example. To obtain approx. 100 MHz-driving frequency, the required on-state current is at least several microamperes. The voltage level difference in the word line, VDDH VSSL, is a factor that determines the on-state current, and in this work is fixed to 3.3 V so that the combination of Vbg and the word line voltage is optimized. The application of negative voltage to the word line enables the leakage current of the cell transistor to be maintained low even when Vbg is increased. For example, whereas the existing driving method meets the above off-state current value with Vbg -7.0 V and the VSSL 0 V, the novel driving method meets the value with Vbg 0 V and VSSL -1.5 V. In the novel driving method, VDDH 1.8 V. There has been a report of a reduction in leakage current of a memory cell by application of negative voltage to a top gate in DRAM using Si CMOS [3]. In contrast to it, DOSRAM including CAAC-IGZO FETs with L 60 nm has a leakage current of 200 zA or lower, which is 7-digit lower than that of the DRAM using Si CMOS, and enables longer data retention. The evaluation results of the prototyped DOSRAM verify that a reduction in power-supply voltage from 3.3 V to 1.8 V is possible in terms of operation and data retention. This suggests a highly compatible and efficient configuration of an embedded DRAM and a logic circuit where signals can be transmitted with low VDD. References [1] S. H. Wu, et al., IEEE Symp. VLSI Tech., pp. 166-167, 2017. [2] T. Ishizu, et al., IEEE Symp. VLSI Cir., pp. 162-163, 2017. [3] F. Hamzaoglu et al., IEEE Journal of Solid-State Circuits, vol. 50, no. 1, pp. 150-157, Jan. 2015