Estimating jet power in proton blazar models

© Copyright © 2002. Astronomical Society of the Pacific. All rights reserved. Printed in U.S.A. Submitted to Cornell University’s online archive www.arXiv.org in 2002 by Ray Protheroe. Post-print sourced from www.arxiv.org.We discuss the various contributions to the jet luminosity in proton blazar models of active galactic nuclei and describe a method of estimating the jet luminosity from the observed spectral energy distribution (SED) and the fitted model parameters. We apply this to a synchrotron proton blazar (SPB) model for Markarian 501.R.J. Protheroe, A. Mück

Increasing the Receptor Tyrosine Kinase EphB2 Prevents Amyloid-β-induced Depletion of Cell Surface Glutamate Receptors by a Mechanism That Requires the PDZ-binding Motif of EphB2 and Neuronal Activity.

Diverse lines of evidence suggest that amyloid-β (Aβ) peptides causally contribute to the pathogenesis of Alzheimer disease (AD), the most frequent neurodegenerative disorder. However, the mechanisms by which Aβ impairs neuronal functions remain to be fully elucidated. Previous studies showed that soluble Aβ oligomers interfere with synaptic functions by depleting NMDA-type glutamate receptors (NMDARs) from the neuronal surface and that overexpression of the receptor tyrosine kinase EphB2 can counteract this process. Through pharmacological treatments and biochemical analyses of primary neuronal cultures expressing wild-type or mutant forms of EphB2, we demonstrate that this protective effect of EphB2 depends on its PDZ-binding motif and the presence of neuronal activity but not on its kinase activity. We further present evidence that the protective effect of EphB2 may be mediated by the AMPA-type glutamate receptor subunit GluA2, which can become associated with the PDZ-binding motif of EphB2 through PDZ domain-containing proteins and can promote the retention of NMDARs in the membrane. In addition, we show that the Aβ-induced depletion of surface NMDARs does not depend on several factors that have been implicated in the pathogenesis of Aβ-induced neuronal dysfunction, including aberrant neuronal activity, tau, prion protein (PrP(C)), and EphB2 itself. Thus, although EphB2 does not appear to be directly involved in the Aβ-induced depletion of NMDARs, increasing its expression may counteract this pathogenic process through a neuronal activity- and PDZ-dependent regulation of AMPA-type glutamate receptors

Statistics of Cosmological Black Hole Jet Sources: Blazar Predictions for GLAST

A study of the statistics of cosmological black-hole jet sources is applied to EGRET blazar data, and predictions are made for GLAST. Black-hole jet sources are modeled as collimated relativistic plasma outflows with radiation beamed along the jet axis due to strong Doppler boosting. The comoving rate density of blazar flares is assumed to follow a blazar formation rate (BFR), modeled by analytic functions based on astronomical observations and fits to EGRET data. The redshift and size distributions of gamma-ray blazars observed with EGRET, separated into BL Lac object (BL) and flat spectrum radio quasar (FSRQ) distributions, are fit with monoparametric functions for the distributions of the jet Lorentz factor \Gamma, comoving directional power l'_e, and spectral slope. A BFR factor ~10 x greater at z ~ 1 than at present is found to fit the FSRQ data. A smaller comoving rate density and greater luminosity of BL flares at early times compared to the present epoch fits the BL data. Based on the EGRET observations, ~1000 blazars consisting of ~800 FSRQs and FR2 radio galaxies and ~200 BL Lacs and FR1 radio galaxies will be detected with GLAST during the first year of the mission. Additional AGN classes, such as hard-spectrum BL Lacs that were mostly missed with EGRET, could add more GLAST sources. The FSRQ and BL contributions to the EGRET gamma-ray background at 1 GeV are estimated at the level of ~10 - 15% and ~2 - 4%, respectively. EGRET and GLAST sensitivities to blazar flares are considered in the optimal case, and a GLAST analysis method for blazar detection is outlined.Comment: 17 pages, 9 figures, ApJ, in press, v.660, May 1, 2007 (minor changes from previous version

Early neuronal accumulation of DNA double strand breaks in Alzheimer's disease.

The maintenance of genomic integrity is essential for normal cellular functions. However, it is difficult to maintain over a lifetime in postmitotic cells such as neurons, in which DNA damage increases with age and is exacerbated by multiple neurological disorders, including Alzheimer's disease (AD). Here we used immunohistochemical staining to detect DNA double strand breaks (DSBs), the most severe form of DNA damage, in postmortem brain tissues from patients with mild cognitive impairment (MCI) or AD and from cognitively unimpaired controls. Immunostaining for γH2AX-a post-translational histone modification that is widely used as a marker of DSBs-revealed increased proportions of γH2AX-labeled neurons and astrocytes in the hippocampus and frontal cortex of MCI and AD patients, as compared to age-matched controls. In contrast to the focal pattern associated with DSBs, some neurons and glia in humans and mice showed diffuse pan-nuclear patterns of γH2AX immunoreactivity. In mouse brains and primary neuronal cultures, such pan-nuclear γH2AX labeling could be elicited by increasing neuronal activity. To assess whether pan-nuclear γH2AX represents DSBs, we used a recently developed technology, DNA damage in situ ligation followed by proximity ligation assay, to detect close associations between γH2AX sites and free DSB ends. This assay revealed no evidence of DSBs in neurons or astrocytes with prominent pan-nuclear γH2AX labeling. These findings suggest that focal, but not pan-nuclear, increases in γH2AX immunoreactivity are associated with DSBs in brain tissue and that these distinct patterns of γH2AX formation may have different causes and consequences. We conclude that AD is associated with an accumulation of DSBs in vulnerable neuronal and glial cell populations from early stages onward. Because of the severe adverse effects this type of DNA damage can have on gene expression, chromatin stability and cellular functions, DSBs could be an important causal driver of neurodegeneration and cognitive decline in this disease

Point-like gamma ray sources as signatures of distant accelerators of ultra high energy cosmic rays

We discuss the possibility of observing distant accelerators of ultra high energy cosmic rays in synchrotron gamma rays. Protons propagating away from their acceleration sites produce extremely energetic electrons during photo-pion interactions with cosmic microwave background photons. If the accelerator is embedded in a magnetized region, these electrons will emit high energy synchrotron radiation. The resulting synchrotron source is expected to be point-like and detectable in the GeV-TeV energy range if the magnetic field is at the nanoGauss level.Comment: 4 pages 2 figures. To be published in PR

Dynamin-related protein 1 is required for normal mitochondrial bioenergetic and synaptic function in CA1 hippocampal neurons.

Disrupting particular mitochondrial fission and fusion proteins leads to the death of specific neuronal populations; however, the normal functions of mitochondrial fission in neurons are poorly understood, especially in vivo, which limits the understanding of mitochondrial changes in disease. Altered activity of the central mitochondrial fission protein dynamin-related protein 1 (Drp1) may contribute to the pathophysiology of several neurologic diseases. To study Drp1 in a neuronal population affected by Alzheimer's disease (AD), stroke, and seizure disorders, we postnatally deleted Drp1 from CA1 and other forebrain neurons in mice (CamKII-Cre, Drp1lox/lox (Drp1cKO)). Although most CA1 neurons survived for more than 1 year, their synaptic transmission was impaired, and Drp1cKO mice had impaired memory. In Drp1cKO cell bodies, we observed marked mitochondrial swelling but no change in the number of mitochondria in individual synaptic terminals. Using ATP FRET sensors, we found that cultured neurons lacking Drp1 (Drp1KO) could not maintain normal levels of mitochondrial-derived ATP when energy consumption was increased by neural activity. These deficits occurred specifically at the nerve terminal, but not the cell body, and were sufficient to impair synaptic vesicle cycling. Although Drp1KO increased the distance between axonal mitochondria, mitochondrial-derived ATP still decreased similarly in Drp1KO boutons with and without mitochondria. This indicates that mitochondrial-derived ATP is rapidly dispersed in Drp1KO axons, and that the deficits in axonal bioenergetics and function are not caused by regional energy gradients. Instead, loss of Drp1 compromises the intrinsic bioenergetic function of axonal mitochondria, thus revealing a mechanism by which disrupting mitochondrial dynamics can cause dysfunction of axons

Analyzing the Multiwavelength Spectrum and Variability of BL Lacertae During the July 1997 Outburst

The multiwavelength spectrum of BL Lacertae during its July 1997 outburst is analyzed in terms of different variations of the homogeneous leptonic jet model for the production of high-energy radiation from blazars. We find that a two-component gamma-ray spectrum, consisting of a synchrotron self-Compton and an external Compton component, is required in order to yield an acceptable fit to the broadband spectrum. Our analysis indicates that in BL Lac, unlike other BL Lac objects, the broad emission line region plays an important role for the high-energy emission. Several alternative blazar jet models are briefly discussed. In the appendix, we describe the formalism in which the process of Comptonization of reprocessed accretion disk photons is treated in the previously developed blazar jet simulation code which we use.Comment: Now accepted for publication in The Astronomical Journal. Significantly extended discussion w.r.t. original version. 3 Figures included using epsf.sty, rotate.st

The AGASA/SUGAR Anisotropies and TeV Gamma Rays from the Galactic Center: A Possible Signature of Extremely High-energy Neutrons

Recent analysis of data sets from two extensive air shower cosmic ray detectors shows tantalizing evidence of an anisotropic overabundance of cosmic rays towards the Galactic Center (GC) that ``turns on'' around $10^{18}$ eV. We demonstrate that the anisotropy could be due to neutrons created at the Galactic Center through charge-exchange in proton-proton collisions, where the incident, high energy protons obey an $\sim E^{-2}$ power law associated with acceleration at a strong shock. We show that the normalization supplied by the gamma-ray signal from EGRET GC source 3EG J1746-2851 -- ascribed to pp induced neutral pion decay at GeV energies -- together with a very reasonable spectral index of 2.2, predicts a neutron flux at $\sim 10^{18}$ eV fully consistent with the extremely high energy cosmic ray data. Likewise, the normalization supplied by the very recent GC data from the HESS air-Cerenkov telescope at \~TeV energies is almost equally-well compatible with the $\sim 10^{18}$ eV cosmic ray data. Interestingly, however, the EGRET and HESS data appear to be themselves incompatible. We consider the implications of this discrepancy. We discuss why the Galactic Center environment can allow diffusive shock acceleration at strong shocks up to energies approaching the ankle in the cosmic ray spectrum. Finally, we argue that the shock acceleration may be occuring in the shell of Sagittarius A East, an unusual supernova remnant located very close to the Galactic Center. If this connection between the anisotropy and Sagittarius A East could be firmly established it would be the first direct evidence for a particular Galactic source of cosmic rays up to energies near the ankle.Comment: 57 pages, 2 figure

EGRET Observations of the Extragalactic Gamma Ray Emission

The all-sky survey in high-energy gamma rays (E$>$30 MeV) carried out by the Energetic Gamma Ray Experiment Telescope (EGRET) aboard the Compton Gamma-Ray Observatory provides a unique opportunity to examine in detail the diffuse gamma-ray emission. The observed diffuse emission has a Galactic component arising from cosmic-ray interactions with the local interstellar gas and radiation as well an almost uniformly distributed component that is generally believed to originate outside the Galaxy. Through a careful study and removal of the Galactic diffuse emission, the flux, spectrum and uniformity of the extragalactic emission is deduced. The analysis indicates that the extragalactic emission is well described by a power law photon spectrum with an index of -(2.10+-0.03) in the 30 MeV to 100 GeV energy range. No large scale spatial anisotropy or changes in the energy spectrum are observed in the deduced extragalactic emission. The most likely explanation for the origin of this extragalactic high-energy gamma-ray emission is that it arises primarily from unresolved gamma-ray-emitting blazars.Comment: 19 pages latex, 10 figures, accepted for publication in Ap

Astrocytic gap junctional communication is reduced in amyloid-β-treated cultured astrocytes, but not in Alzheimer's disease transgenic mice

Alzheimer's disease is characterized by accumulation of amyloid deposits in brain, progressive cognitive deficits and reduced glucose utilization. Many consequences of the disease are attributed to neuronal dysfunction, but roles of astrocytes in its pathogenesis are not well understood. Astrocytes are extensively coupled via gap junctions, and abnormal trafficking of metabolites and signalling molecules within astrocytic syncytia could alter functional interactions among cells comprising the neurovascular unit. To evaluate the influence of amyloid-β on astrocyte gap junctional communication, cultured astrocytes were treated with monomerized amyloid-β1–40 (1 μmol/l) for intervals ranging from 2 h to 5 days, and the areas labelled by test compounds were determined by impaling a single astrocyte with a micropipette and diffusion of material into coupled cells. Amyloid-β-treated astrocytes had rapid, sustained 50–70% reductions in the area labelled by Lucifer Yellow, anionic Alexa Fluor® dyes and energy-related compounds, 6-NBDG (a fluorescent glucose analogue), NADH and NADPH. Amyloid-β treatment also caused a transient increase in oxidative stress. In striking contrast with these results, spreading of Lucifer Yellow within astrocytic networks in brain slices from three regions of 8.5–14-month-old control and transgenic Alzheimer's model mice was variable, labelling 10–2000 cells; there were no statistically significant differences in the number of dye-labelled cells among the groups or with age. Thus amyloid-induced dysfunction of gap junctional communication in cultured astrocytes does not reflect the maintenance of dye transfer through astrocytic syncytial networks in transgenic mice; the pathophysiology of Alzheimer's disease is not appropriately represented by the cell culture system