Gamma-Ray Studies of Blazars: Synchro-Compton Analysis of Flat Spectrum Radio Quasars

We extend a method for modeling synchrotron and synchrotron self-Compton radiations in blazar jets to include external Compton processes. The basic model assumption is that the blazar radio through soft X-ray flux is nonthermal synchrotron radiation emitted by isotropically-distributed electrons in the randomly directed magnetic field of outflowing relativistic blazar jet plasma. Thus the electron distribution is given by the synchrotron spectrum, depending only on the Doppler factor $\delta_{\rm D}$ and mean magnetic field $B$, given that the comoving emission region size scale R_b^\prime \lesssim c \dD t_v/(1+z), where $t_v$ is variability time and $z$ is source redshift. Generalizing the approach of Georganopoulos, Kirk, and Mastichiadis (2001) to arbitrary anisotropic target radiation fields, we use the electron spectrum implied by the synchrotron component to derive accurate Compton-scattered $\gamma$-ray spectra throughout the Thomson and Klein-Nishina regimes for external Compton scattering processes. We derive and calculate accurate $\gamma$-ray spectra produced by relativistic electrons that Compton-scatter (i) a point source of radiation located radially behind the jet, (ii) photons from a thermal Shakura-Sunyaev accretion disk and (iii) target photons from the central source scattered by a spherically-symmetric shell of broad line region (BLR) gas. Calculations of broadband spectral energy distributions from the radio through $\gamma$-ray regimes are presented, which include self-consistent $\gamma\gamma$ absorption on the same radiation fields that provide target photons for Compton scattering. Application of this baseline flat spectrum radio/$\gamma$-ray quasar model is considered in view of data from $\gamma$-ray telescopes and contemporaneous multi-wavelength campaigns.Comment: Accepted by ApJ. 22 pages, 12 figures, 2 tables. Minor revisions to figures and tex

Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells

Abstract Background Neuroinflammation plays a vital role in Alzheimer’s disease and other neurodegenerative conditions. Microglia are the resident mononuclear immune cells of the central nervous system, and they play essential roles in the maintenance of homeostasis and responses to neuroinflammation. The orphan G-protein-coupled receptor 55 (GPR55) has been reported to modulate inflammation and is expressed in immune cells such as monocytes and microglia. However, its effects on neuroinflammation, mainly on the production of members of the arachidonic acid pathway in activated microglia, have not been elucidated in detail. Methods In this present study, a series of coumarin derivatives, that exhibit GPR55 antagonism properties, were designed. The effects of these compounds on members of the arachidonic acid cascade were studied in lipopolysaccharide (LPS)-treated primary rat microglia using Western blot, qPCR, and ELISA. Results We demonstrate here that the various compounds with GPR55 antagonistic activities significantly inhibited the release of PGE2 in primary microglia. The inhibition of LPS-induced PGE2 release by the most potent candidate KIT 17 was partially dependent on reduced protein synthesis of mPGES-1 and COX-2. KIT 17 did not affect any key enzyme involved on the endocannabinoid system. We furthermore show that microglia expressed GPR55 and that a synthetic antagonist of the GPR receptor (ML193) demonstrated the same effect of the KIT 17 on the inhibition of PGE2. Conclusions Our results suggest that KIT 17 is acting as an inverse agonist on GPR55 independent of the endocannabinoid system. Targeting GPR55 might be a new therapeutic option to treat neurodegenerative diseases with a neuroinflammatory background such as Alzheimer’s disease, Parkinson, and multiple sclerosis (MS)