LAT Observation of GRBs: Simulations and Sensitivity Studies

The GLAST Large Area Telescope (LAT) is the next generation satellite experiment for high-energy gamma-ray astronomy. It employs a pair conversion technique to record photons in the energy range from 20 MeV to more than 300 GeV. The LAT will follow the steps from its predecessor EGRET (1991-2000), and will explore the high-energy gamma-ray sky with unprecedented capabilities. The observation of Gamma-Ray Bursts is one of the main science goal of the LAT: in this contribution we compute an estimation of the LAT sensitivity to GRB, adopting a phenomenological description of GRBs, where the high-energy emission in GRB is obtained extrapolating the observed BATSE spectrum up to LAT energies. The effect of the cosmological attenuation is included. We use the BATSE current catalog to build up our statistics

Cosmic Ray Electron Science with GLAST

Cosmic ray electrons at high energy carry information about their sources, their diffusion in local magnetic fields and their interactions with the photon fields through which they travel. The spectrum of the particles is affected by inverse Compton losses and synchrotron losses, the rates of which are proportional to the square of the particle's energy making the spectra very steep. However, GLAST will be able to make unique and very high statistics measurements of electrons from {approx}20 to {approx}700 GeV that will allow us to search for anisotropies in arrival direction and spectral features associated with some dark matter candidates. Complementary information on electrons of still higher energy will be required to see effects of possible individual cosmic ray sources

GRB Simulations in GLAST

The Gamma-ray Large Area Space Telescope (GLAST), scheduled to be launched in fall of 2007, is the next generation satellite for high-energy gamma-ray astronomy. The Large Area Telescope (LAT) is a pair conversion telescope built with a high precision silicon tracker, a segmented CsI electromagnetic calorimeter and a plastic anticoincidence shield. The LAT will survey the sky in the energy range between 20 MeV to more than 300 GeV, shedding light on many issues left open by its highly successful predecessor EGRET. LAT will observe Gamma-Ray Bursts (GRB) in an energy range never explored before; to tie these frontier observations to the better-known properties at lower energies, a second instrument, the GLAST Burst Monitor (GBM) will provide important spectra and timing in the 10 keV to 30 MeV range. We briefly present the instruments onboard the GLAST satellite, their synergy in the GRB observations and the work done so far by the collaboration in simulation, analysis, and GRB sensitivity estimation

LAT Onboard Science: Gamma-Ray Burst Identification

The main goal of the Large Area Telescope (LAT) onboard science program is to provide quick identification and localization of Gamma Ray Bursts (GRB) onboard the LAT for follow-up observations by other observatories. The GRB identification and localization algorithm will provide celestial coordinates with an error region that will be distributed via the Gamma ray burst Coordinate Network (GCN). We present results that show our sensitivity to bursts as characterized using Monte Carlo simulations of the GLAST observatory. We describe and characterize the method of onboard track determination and the GRB identification and localization algorithm. Onboard track determination is considerably different than in the onground case, resulting in a substantially altered point spread function. The algorithm contains tunable parameters which may be adjusted after launch when real bursts characteristics at very high energies have been identified

The GLAST Background Model

In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect

A Genome-Wide Analysis of Promoter-Mediated Phenotypic Noise in Escherichia coli

Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as “phenotypic noise.” In bacterial systems, previous studies have shown that, for specific genes, both transcriptional and translational processes affect phenotypic noise. Here, we focus on how the promoter regions of genes affect noise and ask whether levels of promoter-mediated noise are correlated with genes' functional attributes, using data for over 60% of all promoters in Escherichia coli. We find that essential genes and genes with a high degree of evolutionary conservation have promoters that confer low levels of noise. We also find that the level of noise cannot be attributed to the evolutionary time that different genes have spent in the genome of E. coli. In contrast to previous results in eukaryotes, we find no association between promoter-mediated noise and gene expression plasticity. These results are consistent with the hypothesis that, in bacteria, natural selection can act to reduce gene expression noise and that some of this noise is controlled through the sequence of the promoter region alon

Phocid Seal Leptin: Tertiary Structure and Hydrophobic Receptor Binding Site Preservation during Distinct Leptin Gene Evolution

The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids) have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR) binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional surfactant requirement is met by the leptin pulmonary surfactant production pathway which normally appears only to function in the mammalian foetus

Redundancy and the Evolution of Cis-Regulatory Element Multiplicity

The promoter regions of many genes contain multiple binding sites for the same transcription factor (TF). One possibility is that this multiplicity evolved through transitional forms showing redundant cis-regulation. To evaluate this hypothesis, we must disentangle the relative contributions of different evolutionary mechanisms to the evolution of binding site multiplicity. Here, we attempt to do this using a model of binding site evolution. Our model considers binding sequences and their interactions with TFs explicitly, and allows us to cast the evolution of gene networks into a neutral network framework. We then test some of the model's predictions using data from yeast. Analysis of the model suggested three candidate nonadaptive processes favoring the evolution of cis-regulatory element redundancy and multiplicity: neutral evolution in long promoters, recombination and TF promiscuity. We find that recombination rate is positively associated with binding site multiplicity in yeast. Our model also indicated that weak direct selection for multiplicity (partial redundancy) can play a major role in organisms with large populations. Our data suggest that selection for changes in gene expression level may have contributed to the evolution of multiple binding sites in yeast. We conclude that the evolution of cis-regulatory element redundancy and multiplicity is impacted by many aspects of the biology of an organism: both adaptive and nonadaptive processes, both changes in cis to binding sites and in trans to the TFs that interact with them, both the functional setting of the promoter and the population genetic context of the individuals carrying them

The Effect of Inappropriate Calibration: Three Case Studies in Molecular Ecology

Time-scales estimated from sequence data play an important role in molecular ecology. They can be used to draw correlations between evolutionary and palaeoclimatic events, to measure the tempo of speciation, and to study the demographic history of an endangered species. In all of these studies, it is paramount to have accurate estimates of time-scales and substitution rates. Molecular ecological studies typically focus on intraspecific data that have evolved on genealogical scales, but often these studies inappropriately employ deep fossil calibrations or canonical substitution rates (e.g., 1% per million years for birds and mammals) for calibrating estimates of divergence times. These approaches can yield misleading estimates of molecular time-scales, with significant impacts on subsequent evolutionary and ecological inferences. We illustrate this calibration problem using three case studies: avian speciation in the late Pleistocene, the demographic history of bowhead whales, and the Pleistocene biogeography of brown bears. For each data set, we compare the date estimates that are obtained using internal and external calibration points. In all three cases, the conclusions are significantly altered by the application of revised, internally-calibrated substitution rates. Collectively, the results emphasise the importance of judicious selection of calibrations for analyses of recent evolutionary events