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

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

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

EGRET Spectral Index and the Low-Energy Peak Position in the Spectral Energy Distribution of EGRET-Detected Blazars

In current theoretical models of the blazar subclass of active galaxies, the broadband emission consists of two components: a low-frequency synchrotron component with a peak in the IR to X-ray band, and a high-frequency inverse Compton component with a peak in the gamma-ray band. In such models, the gamma-ray spectral index should be correlated with the location of the low-energy peak, with flatter gamma-ray spectra expected for blazars with synchrotron peaks at higher photon energies and vice versa. Using the EGRET-detected blazars as a sample, we examine this correlation and possible uncertainties in its construction.Comment: 17 pages including 1 figure, accepted for publication in The Astrophysical Journa

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

The Radio to Gamma Ray Connection of EGRET Blazars: Correlation, Regression and Monte Carlo Analysis

A comprehensive statistical analysis of the broadband properties of EGRET blazars is presented. This analysis includes sources identified as blazars in the Sowards-Emmerd publications. Using this sample of 122 sources, we find that there is a relationship $L_\gamma \propto {L_r}^{0.77 \pm 0.03}$ as well as a correlation between $\alpha_{og}$ and $\alpha_{ro}$, and a correlation between radio luminosity and $\alpha_{og}$. Through the use of Monte Carlo simulations, we can replicate the observed luminosity relationship if a synchrotron self-Compton model is assumed. However, this relationship can not be replicated if an external Compton scattering model is assumed. These differences are primarily due to beaming effects. In addition it has been determined that the intrinsic radio luminosity of the parent sample falls in the range $10^{21} < L < 10^{30} {\rm Watts Hz^{-1}}$ and that the bulk Lorentz factors of the source are in the range $1 < \Gamma < 30$, in a agreement with VLBI observations. Finally, we discuss implications for GLAST, successfully launched in June 2008

Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use