Ebolavirus is evolving but not changing: No evidence for functional change in EBOV from 1976 to the 2014 outbreak

The 2014 epidemic of Ebola virus disease (EVD) has had a devastating impact in West Africa. Sequencing of ebolavirus (EBOV) from infected individuals has revealed extensive genetic variation, leading to speculation that the virus may be adapting to humans, accounting for the scale of the 2014 outbreak. We computationally analyze the variation associated with all EVD outbreaks, and find none of the amino acid replacements lead to identifiable functional changes. These changes have minimal effect on protein structure, being neither stabilizing nor destabilizing, are not found in regions of the proteins associated with known functions and tend to cluster in poorly constrained regions of proteins, specifically intrinsically disordered regions. We find no evidence that the difference between the current and previous outbreaks is due to evolutionary changes associated with transmission to humans. Instead, epidemiological factors are likely to be responsible for the unprecedented spread of EVD

Adaptive HIV-1 evolutionary trajectories are constrained by protein stability

Despite the use of combination antiretroviral drugs for the treatment of HIV-1 infection, the emergence of drug resistance remains a problem. Resistance may be conferred either by a single mutation or a concerted set of mutations. The involvement of multiple mutations can arise due to interactions between sites in the amino acid sequence as a consequence of the need to maintain protein structure. To better understand the nature of such epistatic interactions, we reconstructed the ancestral sequences of HIV-1's Pol protein, and traced the evolutionary trajectories leading to mutations associated with drug resistance. Using contemporary and ancestral sequences we modelled the effects of mutations (i.e. amino acid replacements) on protein structure to understand the functional effects of residue changes. Although the majority of resistance-associated sequences tend to destabilise the protein structure, we find there is a general tendency for protein stability to decrease across HIV-1's evolutionary history. That a similar pattern is observed in the non-drug resistance lineages indicates that non-resistant mutations, for example, associated with escape from the immune response, also impacts on protein stability. Maintenance of optimal protein structure therefore represents a major constraining factor to the evolution of HIV-1

One-nucleon transfer reactions and the optical potential

We provide a summary of new developments in the area of direct reaction theory with a particular focus on one-nucleon transfer reactions. We provide a status of the methods available for describing (d,p) reactions. We discuss the effects of nonlocality in the optical potential in transfer reactions. The results of a purely phenomenological potential and the optical potential obtained from the dispersive optical model are compared; both point toward the importance of including nonlocality in transfer reactions explicitly. Given the large ambiguities associated with optical potentials, we discuss some new developments toward the quantification of this uncertainty. We conclude with some general comments and a brief account of new advances that are in the pipeline.Comment: 7 pages, 5 figures, proceedings for the 14th International Conference on Nuclear Reaction Mechanisms, Varenna, June 201

A Compact Extreme Scattering Event Cloud Towards AO 0235+164

We present observations of a rare, rapid, high amplitude Extreme Scattering Event toward the compact BL-Lac AO 0235+164 at 6.65 GHz. The ESE cloud is compact; we estimate its diameter between 0.09 and 0.9 AU, and is at a distance of less than 3.6 kpc. Limits on the angular extent of the ESE cloud imply a minimum cloud electron density of ~ 4 x 10^3 cm^-3. Based on the amplitude and timescale of the ESE observed here, we suggest that at least one of the transients reported by Bower et al. (2007) may be attributed to ESEs.Comment: 11 pages, 2 figure

Continuing a Chandra Survey of Quasar Radio Jets

We are conducting an X-ray survey of flat spectrum radio quasars (FSRQs) with extended radio structures. We summarize our results from the first stage of our survey, then we present findings from its continuation. We have discovered jet X-ray emission from 12 of our first 20 Chandra targets, establishing that strong 0.5-7.0 keV emission is a common feature of FSRQ jets. The X-ray morphology is varied, but in general closely matches the radio structure until the first sharp radio bend. In the sources with optical data as well as X-ray detections we rule out simple synchrotron models for X-ray emission, suggesting these systems may instead be dominated by inverse Compton (IC) scattering. Fitting models of IC scattering of cosmic microwave background photons suggests that these jets are aligned within a few degrees of our line of sight, with bulk Lorentz factors of a few to ten and magnetic fields a bit stronger than $10^{-5}$ G. In the weeks prior to this meeting, we have discovered two new X-ray jets at $z > 1$. One (PKS B1055+201) has a dramatic, $20''$-long jet. The other (PKS B1421-490) appears unremarkable at radio frequencies, but at higher frequencies the jet is uniquely powerful: its optically-dominated, with jet/core flux ratios of 3.7 at 1 keV and 380 at 480 nm.Comment: 4 pages, 8 figures. To appear in `X-Ray and Radio Connections', ed. L.O. Sjouwerman and K.K. Dyer (published electronicly at http://www.aoc.nrao.edu/events/xraydio/). Additional material and higher resolution figures may be found at http://space.mit.edu/home/jonathan/jets

On the Significance of Rare Objects at High Redshift: The Impact of Cosmic Variance

The discovery of extremely luminous galaxies at ultra-high redshifts ($z\gtrsim 8$) has posed a challenge for galaxy formation models. Most statistical analyses of this tension to date have not properly accounted for the variance due to field-to-field clustering, which causes the number counts of galaxies to vary from field to field, greatly in excess of Poisson noise. This super-Poissonian variance is often referred to as cosmic variance. Since cosmic variance increases rapidly as a function of mass, redshift, and for small observing areas, the most massive objects in deep \textit{JWST} surveys are severely impacted by cosmic variance. In this paper, we introduce a simple model to predict the distribution of the mass of the most massive galaxy found for different survey designs, which includes cosmic variance. The distributions differ significantly from previous predictions using the Extreme Value Statistics formalism, changing both the position and shape of the distribution of most massive galaxies in a counter-intuitive way. We test our model using the \texttt{UniverseMachine} simulations, where the predicted effects of including cosmic variance are clearly identifiable. Moreover, we find that the highly significant skew in the distributions of galaxy number counts for typical deep \textit{JWST} surveys lead to a high "variance on the variance", which greatly impacts the calculation of the cosmic variance itself. We conclude that it is crucial to accurately account for the impact of cosmic variance in any future analysis of tension between extreme galaxies in the early universe and galaxy formation models.Comment: Submitted to ApJ. The main text contains 15 pages and 9 figures. The appendix contains 4 pages and 3 figure