A Multiwavelength Investigation of Unidentified EGRET Sources

Statistical studies indicate that the 271 point sources of high-energy gamma rays belong to two groups: a Galactic population and an isotropic extragalactic population. Many unidentified extragalactic sources are certainly blazars, and it is the intention of this work to uncover gamma-ray blazars missed by previous attempts. Until recently, searches for blazar counterparts to unidentified EGRET sources have focused on finding AGN that have 5-GHz radio flux densities S_5 near or above 1 Jy. However, the recent blazar identification of 3EG J2006-2321 (S_5 = 260 mJy) and other work suggest that careful studies of weaker flat-spectrum sources may be fruitful. In this spirit, error circles of 4 high-latitude unidentified EGRET sources have been searched for 5-GHz sources. The gamma-ray sources are 3EG J1133+0033, 3EG J1212+2304, 3EG J1222+2315, and 3EG J1227+4302. Within the error contours of each of the four sources are found 6 radio candidates; by observing the positions of the radio sources with the 0.81-m Tenagra II telescope it is determined that 14 of these 24 radio sources have optical counterparts with R < 22. Eight of these from two different EGRET sources have been observed in the B, V, and R bands in more than one epoch and the analysis of these data is ongoing. Any sources that are found to be variable will be the objects of multi-epoch polarimetry studies.Comment: 6 pages, 2 tables. To appear in Astrophysics & Space Scienc

Intrinsic and Cosmological Signatures in Gamma-Ray Burst Time Profiles: Time Dilation

The time profiles of many gamma-ray bursts consist of distinct pulses, which offers the possibility of characterizing the temporal structure of these bursts using a relatively small set of pulse shape parameters. We have used a pulse decomposition procedure to analyze the Time-to-Spill (TTS) data for all bursts observed by BATSE up through trigger number 2000, in all energy channels for which TTS data is available. We obtain amplitude, rise and decay timescales, a pulse shape parameter, and the fluences of individual pulses in all of the bursts. We investigate the correlations between brightness measures (amplitude and fluence) and timescale measures (pulse width and separation) which may result from cosmological time dilation of bursts, or from intrinsic properties of burst sources or from selection effects. The effects of selection biases are evaluated through simulations. The correlations between these parameters among pulses within individual bursts give a measure of the intrinsic effects while the correlations among bursts could result both from intrinsic and cosmological effects. We find that timescales tend to be shorter in bursts with higher peak fluxes, as expected from cosmological time dilation effects, but also find that there are non-cosmological effects contributing to this inverse correlation. We find that timescales tend to be longer in bursts with higher total fluences, contrary to what is expected from cosmological effects. We also find that peak fluxes and total fluences of bursts are uncorrelated, indicating that they cannot both be good distance indicators for bursts.Comment: 39 pages, 17 figures composed of 30 EPS files. Submitted to Astrophysical Journal. PostScript and PDF with un-bitmapped figures available at http://www.slac.stanford.edu/pubs/slacpubs/8000/slac-pub-8365.html . Accompanies astro-ph/000221

Geography, Demography, and Economic Growth in Africa

macroeconomics, Geography, Demography, Economic Growth, Africa

A Computational-Experimental Approach Identifies Mutations That Enhance Surface Expression of an Oseltamivir-Resistant Influenza Neuraminidase

The His274 → Tyr (H274Y) oseltamivir (Tamiflu) resistance mutation causes a substantial decrease in the total levels of surface-expressed neuraminidase protein and activity in early isolates of human seasonal H1N1 influenza, and in the swine-origin pandemic H1N1. In seasonal H1N1, H274Y only became widespread after the occurrence of secondary mutations that counteracted this decrease. H274Y is currently rare in pandemic H1N1, and it remains unclear whether secondary mutations exist that might similarly counteract the decreased neuraminidase surface expression associated with this resistance mutation in pandemic H1N1. Here we investigate the possibility of predicting such secondary mutations. We first test the ability of several computational approaches to retrospectively identify the secondary mutations that enhanced levels of surface-expressed neuraminidase protein and activity in seasonal H1N1 shortly before the emergence of oseltamivir resistance. We then use the most successful computational approach to predict a set of candidate secondary mutations to the pandemic H1N1 neuraminidase. We experimentally screen these mutations, and find that several of them do indeed partially counteract the decrease in neuraminidase surface expression caused by H274Y. Two of the secondary mutations together restore surface-expressed neuraminidase activity to wildtype levels, and also eliminate the very slight decrease in viral growth in tissue-culture caused by H274Y. Our work therefore demonstrates a combined computational-experimental approach for identifying mutations that enhance neuraminidase surface expression, and describes several specific mutations with the potential to be of relevance to the spread of oseltamivir resistance in pandemic H1N1

Hard gamma ray emission from blazars

The gamma-ray emission expected from compact extragalactic sources of nonthermal radiation is examined. The highly variable objects in this class should produce copious amounts of self-Compton gamma-rays in the compact relativistic jet. This is shown to be a likely interpretation of the hard gamma-ray emission recently detected from the quasar 3C 279 during a period of strong nonthermal flaring at lower frequencies. Ways of discriminating between the self-Compton model and other possible gamma-ray emission mechanisms are discussed

Expected level of self-Compton scattering in radio loud quasars

Radio-loud quasars usually contain parsec-scale nonthermal jets. The most compact emission region ('the core'), and perhaps some of the moving 'knots', are expected to be efficient producers of inverse Compton scattered X-rays and gamma-rays since many of the synchrotron photons will upscatter before escaping. Through multifrequency flux density observations and Very Long Baseline Interferometry (VLBI) measurements of angular sizes, one can predict the flux density of this self-Compton high-energy emission. It is not always the case that the brightest synchrotron sources are also the brightest X-ray and gamma-ray sources. Perhaps a better predictor of high-energy brightness is the ratio of hard X-ray to high-frequency radio emission. Using the synchrotron self-Compton relations, we predict the gamma-ray fluxes of several sources we expect to be detected by the Energetic Gamma Ray Experiment Telescope (EGRET). More accurate predictions will be made when we complete a program of contemporaneous radio-submillimeter and X-ray observations during the course of the EGRET all-sky survey

Thermodynamics of Neutral Protein Evolution

Naturally evolving proteins gradually accumulate mutations while continuing to fold to thermodynamically stable native structures. This process of neutral protein evolution is an important mode of genetic change, and forms the basis for the molecular clock. Here we present a mathematical theory that predicts the number of accumulated mutations, the index of dispersion, and the distribution of stabilities in an evolving protein population from knowledge of the stability effects (ddG values) for single mutations. Our theory quantitatively describes how neutral evolution leads to marginally stable proteins, and provides formulae for calculating how fluctuations in stability cause an overdispersion of the molecular clock. It also shows that the structural influences on the rate of sequence evolution that have been observed in earlier simulations can be calculated using only the single-mutation ddG values. We consider both the case when the product of the population size and mutation rate is small and the case when this product is large, and show that in the latter case proteins evolve excess mutational robustness that is manifested by extra stability and increases the rate of sequence evolution. Our basic method is to treat protein evolution as a Markov process constrained by a minimal requirement for stable folding, enabling an evolutionary description of the proteins solely in terms of the experimentally measureable ddG values. All of our theoretical predictions are confirmed by simulations with model lattice proteins. Our work provides a mathematical foundation for understanding how protein biophysics helps shape the process of evolution

Stability-mediated epistasis constrains the evolution of an influenza protein.

John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value. DOI:http://dx.doi.org/10.7554/eLife.00631.001