Unidentified EGRET Sources and the Extragalactic Gamma-Ray Background

The large majority of EGRET point sources remain to this day without an identified low-energy counterpart. Whatever the nature of the EGRET unidentified sources, faint unresolved objects of the same class must have a contribution to the diffuse gamma-ray background: if most unidentified objects are extragalactic, faint unresolved sources of the same class contribute to the background, as a distinct extragalactic population; on the other hand, if most unidentified sources are Galactic, their counterparts in external galaxies will contribute to the unresolved emission from these systems. Understanding this component of the gamma-ray background, along with other guaranteed contributions from known sources, is essential in any attempt to use gamma-ray observations to constrain exotic high-energy physics. Here, we follow an empirical approach to estimate whether a potential contribution of unidentified sources to the extragalactic gamma-ray background is likely to be important, and we find that it is. Additionally, we comment on how the anticipated GLAST measurement of the diffuse gamma-ray background will change, depending on the nature of the majority of these sources.Comment: 6 pages, 3 figures, to appear in proceedings of "The Multi-Messenger Approach to High Energy Gamma-Ray Sources", Barcelona, 4-7 July 2006; comments welcom

Why I tense up when you watch me: inferior parietal cortex mediates an audience’s influence on motor performance

The presence of an evaluative audience can alter skilled motor performance through changes in force output. To investigate how this is mediated within the brain, we emulated real-time social monitoring of participants’ performance of a fine grip task during functional magnetic resonance neuroimaging. We observed an increase in force output during social evaluation that was accompanied by focal reductions in activity within bilateral inferior parietal cortex. Moreover, deactivation of the left inferior parietal cortex predicted both inter- and intra-individual differences in socially-induced change in grip force. Social evaluation also enhanced activation within the posterior superior temporal sulcus, which conveys visual information about others’ actions to the inferior parietal cortex. Interestingly, functional connectivity between these two regions was attenuated by social evaluation. Our data suggest that social evaluation can vary force output through the altered engagement of inferior parietal cortex; a region implicated in sensorimotor integration necessary for object manipulation, and a component of the action-observation network which integrates and facilitates performance of observed actions. Social-evaluative situations may induce high-level representational incoherence between one’s own intentioned action and the perceived intention of others which, by uncoupling the dynamics of sensorimotor facilitation, could ultimately perturbe motor output

Dark Matter Annihilation around Intermediate Mass Black Holes: an update

The formation and evolution of Black Holes inevitably affects the distribution of dark and baryonic matter in the neighborhood of the Black Hole. These effects may be particularly relevant around Supermassive and Intermediate Mass Black Holes (IMBHs), the formation of which can lead to large Dark Matter overdensities, called {\em spikes} and {\em mini-spikes} respectively. Despite being larger and more dense, spikes evolve at the very centers of galactic halos, in regions where numerous dynamical effects tend to destroy them. Mini-spikes may be more likely to survive, and they have been proposed as worthwhile targets for indirect Dark Matter searches. We review here the formation scenarios and the prospects for detection of mini-spikes, and we present new estimates for the abundances of mini-spikes to illustrate the sensitivity of such predictions to cosmological parameters and uncertainties regarding the astrophysics of Black Hole formation at high redshift. We also connect the IMBHs scenario to the recent measurements of cosmic-ray electron and positron spectra by the PAMELA, ATIC, H.E.S.S., and Fermi collaborations.Comment: 12 pages, 7 figures. Invited contribution to NJP Focus Issue on "Dark Matter and Particle Physics

Bright AGN Source List from the First Three Months of the Fermi Large Area Telescope All-Sky Survey

The first three months of sky-survey operation with the Fermi Gamma Ray Space Telescope (Fermi) Large Area Telescope (LAT) reveals 132 bright sources at |b|>10 deg with test statistic greater than 100 (corresponding to about 10 sigma). Two methods, based on the CGRaBS, CRATES and BZCat catalogs, indicate high-confidence associations of 106 of these sources with known AGNs. This sample is referred to as the LAT Bright AGN Sample (LBAS). It contains two radio galaxies, namely Centaurus A and NGC 1275, and 104 blazars consisting of 57 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and 5 blazars with uncertain classification. Four new blazars were discovered on the basis of the LAT detections. Remarkably, the LBAS includes 10 high-energy peaked BL Lacs (HBLs), sources which were so far hard to detect in the GeV range. Another 10 lower-confidence associations are found. Only thirty three of the sources, plus two at |b|>10 deg, were previously detected with EGRET, probably due to the variable nature of these sources. The analysis of the gamma-ray properties of the LBAS sources reveals that the average GeV spectra of BL Lac objects are significantly harder than the spectra of FSRQs. No significant correlation between radio and peak gamma-ray fluxes is observed. Blazar log N - log S and luminosity functions are constructed to investigate the evolution of the different blazar classes, with positive evolution indicated for FSRQs but none for BLLacs. The contribution of LAT-blazars to the total extragalactic gamma-ray intensity is estimated.Comment: Submitted to ApJ. Not yet refereed. 61 pages, 26 figure

The Luminosity Function of Fermi-detected Flat-Spectrum Radio Quasars

Fermi has provided the largest sample of {\gamma}-ray selected blazars to date. In this work we use a complete sample of FSRQs detected during the first year of operation to determine the luminosity function (LF) and its evolution with cosmic time. The number density of FSRQs grows dramatically up to redshift \sim0.5-2.0 and declines thereafter. The redshift of the peak in the density is luminosity dependent, with more luminous sources peaking at earlier times; thus the LF of {\gamma}-ray FSRQs follows a luminosity-dependent density evolution similarly to that of radio-quiet AGN. Also using data from the Swift Burst Alert Telescope we derive the average spectral energy distribution of FSRQs in the 10 keV-100 GeV band and show that there is no correlation of the peak {\gamma}-ray luminosity with {\gamma}-ray peak frequency. The coupling of the SED and LF allows us to predict that the contribution of FSRQs to the Fermi isotropic {\gamma}-ray background is 9.3(+1.6/-1.0) (\pm3% systematic uncertainty) in the 0.1-100GeV band. Finally we determine the LF of unbeamed FSRQs, finding that FSRQs have an average Lorentz factor of {\gamma} = 11.7(+3.3/-2.2), that most are seen within 5\circ of the jet axis, and that they represent only ~0.1 % of the parent population.Comment: Submitted to the Astrophysical Journa

The Fermi-LAT high-latitude Survey: Source Count Distributions and the Origin of the Extragalactic Diffuse Background

This is the first of a series of papers aimed at characterizing the populations detected in the high-latitude sky of the {\it Fermi}-LAT survey. In this work we focus on the intrinsic spectral and flux properties of the source sample. We show that when selection effects are properly taken into account, {\it Fermi} sources are on average steeper than previously found (e.g. in the bright source list) with an average photon index of 2.40$\pm0.02$ over the entire 0.1--100\,GeV energy band. We confirm that FSRQs have steeper spectra than BL Lac objects with an average index of 2.48$\pm0.02$ versus 2.18$\pm0.02$. Using several methods we build the deepest source count distribution at GeV energies deriving that the intrinsic source (i.e. blazar) surface density at F$_{100}\geq10^{-9}$\,ph cm$^{-2}$ s$^{-1}$ is 0.12$^{+0.03}_{-0.02}$\,deg$^{-2}$. The integration of the source count distribution yields that point sources contribute 16$(\pm1.8)$\,\% ($\pm$7\,\% systematic uncertainty) of the GeV isotropic diffuse background. At the fluxes currently reached by LAT we can rule out the hypothesis that point-like sources (i.e. blazars) produce a larger fraction of the diffuse emission.Comment: Version replaced to match the published one. Contact authors: M. Ajello and A. Tramacer

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The role of CCR7 in allergic airway inflammation induced by house dust mite exposure

House dust mite (HDM), the most common allergen, activate both the IgE-associated and innate immune responses. To clarify the process of sensitization, we investigated the role of the CCL21, CCL19, and CCR7 axis in a mouse model of HDM-induced allergic asthma. HDM inhalation without systemic immunization resulted in a HDM-specific IgE response. CCR7-knockout (CCR7KO) mice exhibited greater airway inflammation and IgE responses compared to wild-type mice. We examined FoxP3 expression in these mice to clarify the contribution of regulatory cells to the responses. FoxP3 expression was higher in the lungs but not in the lymph nodes of CCR7KO mice compared to wild-type mice. In CCR7KO mice, FoxP3-positive cells were found in lung, but we observed higher release of IL-13, IL-5, TGF-beta, IL-17, and HMGB1 in bronchoalveolar lavage fluid. We demonstrate here that immuno-regulation through CCR7 expression in T cells plays a role in HDM-specific sensitization in the airway