Electron cryo-tomography studies of maturing HIV-1 particles reveal the assembly pathway of the viral core

To better characterize the assembly of the HIV-1 core, we have used electron cryo-tomography (ECT) to image infected cells and the viral particles cryo-preserved next to them. We observed progressive stages of virus assembly and egress including flower-like flat gag lattice assemblies, hemispherical budding profiles and virus buds linked to the plasma membrane via a thin membrane neck. The population of budded viral particles contains immature, maturation intermediate and mature core morphologies. Structural characteristics of the maturation intermediates suggest that the core assembly pathway involves the formation of a CA sheet that associates with the condensed ribonucleoprotein (RNP) complex. Our analysis also reveals a correlation between RNP localization within the viral particle and the formation of conical cores, suggesting that the RNP helps drive conical core assembly. Our findings support an assembly pathway for the HIV-1 core that begins with a small CA sheet that associates with the RNP to form the core base, followed by polymerization of the CA sheet along one side of the conical core towards the tip and then closure around the body of the cone

Chemo-Archaeological Downsizing in a Hierarchical Universe: Impact of a Top Heavy IGIMF

We make use of a semi-analytical model of galaxy formation to investigate the origin of the observed correlation between [a/Fe] abundance ratios and stellar mass in elliptical galaxies. We implement a new galaxy-wide stellar initial mass function (Top Heavy Integrated Galaxy Initial Mass Function, TH-IGIMF) in the semi-analytic model SAG and evaluate its impact on the chemical evolution of galaxies. The SFR-dependence of the slope of the TH-IGIMF is found to be key to reproducing the correct [a/Fe]-stellar mass relation. Massive galaxies reach higher [a/Fe] abundance ratios because they are characterized by more top-heavy IMFs as a result of their higher SFR. As a consequence of our analysis, the value of the minimum embedded star cluster mass and of the slope of the embedded cluster mass function, which are free parameters involved in the TH-IGIMF theory, are found to be as low as 5 solar masses and 2, respectively. A mild downsizing trend is present for galaxies generated assuming either a universal IMF or a variable TH-IGIMF. We find that, regardless of galaxy mass, older galaxies (with formation redshifts > 2) are formed in shorter time-scales (< 2 Gyr), thus achieving larger [a/Fe] values. Hence, the time-scale of galaxy formation alone cannot explain the slope of the [a/Fe]-galaxy mass relation, but is responsible for the big dispersion of [a/Fe] abundance ratios at fixed stellar mass.We further test the hyphothesis of a TH-IGIMF in elliptical galaxies by looking into mass-to-light ratios, and luminosity functions. Models with a TH-IGIMF are also favoured by these constraints. In particular, mass-to-light ratios agree with observed values for massive galaxies while being overpredicted for less massive ones; this overprediction is present regardless of the IMF considered.Comment: 24 pages, 15 figures, 2 tables. (Comments most welcome). Summited to MNRA

A Policy Impact Evaluation Model For Scotland: Decoupling Single Farm Payments

The purpose of this paper is to assess the impacts of decoupling single farm payments in Scotland. It focuses on aggregate impacts on the agricultural products in domestic and external markets and the spill-over effect of this on the non-agricultural sector as well as an aggregate impact on the Scottish GDP. In order to capture system-wide impacts of the policy reform, a CGE model was formulated and implemented using a social accounting matrix constructed for Scotland. The simulation results suggest that the Scottish agricultural sector may encounter declines in output and factor us as a result of the policy reform. However, this critically depends on two factors: (a) the price effect of the policy reform on Scottish agricultural products relative to the EU average as well as the conditions of changes in world agricultural market prices; and (b) the extent to which customers would be sensitive to price effects of the policy reform. As far as the spill-over effect to the non-agricultural sector is concerned, decoupling of direct payments seems to have a positive spill-over effect. Similarly, the aggregate GDP effect is positive under all simulation scenarios. Critically, the simulation experiments indicate that policy shock may have a symmetrical outcome across the two sectors, with contractions in agriculture being accompanied by expansions in the non-agricultural sector, mainly because of factor market interactions between the two sectors.

Calibration of semi-analytic models of galaxy formation using Particle Swarm Optimization

We present a fast and accurate method to select an optimal set of parameters in semi-analytic models of galaxy formation and evolution (SAMs). Our approach compares the results of a model against a set of observables applying a stochastic technique called Particle Swarm Optimization (PSO), a self-learning algorithm for localizing regions of maximum likelihood in multidimensional spaces that outperforms traditional sampling methods in terms of computational cost. We apply the PSO technique to the SAG semi-analytic model combined with merger trees extracted from a standard $\Lambda$CDM N-body simulation. The calibration is performed using a combination of observed galaxy properties as constraints, including the local stellar mass function and the black hole to bulge mass relation. We test the ability of the PSO algorithm to find the best set of free parameters of the model by comparing the results with those obtained using a MCMC exploration. Both methods find the same maximum likelihood region, however the PSO method requires one order of magnitude less evaluations. This new approach allows a fast estimation of the best-fitting parameter set in multidimensional spaces, providing a practical tool to test the consequences of including other astrophysical processes in SAMs.Comment: 11 pages, 4 figures, 1 table. Accepted for publication in ApJ. Comments are welcom

The Role of Gas in the Merging of Massive Black Holes in Galactic Nuclei. I. Black Hole Merging in a Spherical Gas Cloud

Using high-resolution SPH numerical simulations, we investigate the effects of gas on the inspiral and merger of a massive black hole binary. This study is motivated by both observational and theoretical work that indicate the presence of large amounts of gas in the central regions of merging galaxies. N-body simulations have shown that the coalescence of a massive black hole binary eventually stalls in a stellar background. However, our simulations suggest that the massive black hole binary will finally merge if it is embedded in a gaseous background. Here we present results in which the gas is assumed to be initially spherical with a relatively smooth distribution. In the early evolution of the binary, the separation dimishes due to the gravitational drag exerted by the background gas. In the later stages, when the binary dominates the gravitational potential in its vicinity, the medium responds by forming an ellipsoidal density enhancement whose axis lags behind the binary axis, and this offset produces a torque on the binary that causes continuing loss of angular momentum and is able to reduce the binary separation to distances where gravitational radiation is efficient. Assuming typical parameters from observations of Ultra Luminous Infrared Galaxies, we predict that a black hole binary will merge within $10^{7}$yrs; therefore these results imply that in a merger of gas-rich galaxies, any massive central black holes will coalescence soon after the galaxies merge. Our work thus supports scenarios of massive black hole evolution and growth where hierarchical merging plays an important role. The final coalescence of the black holes leads to gravitational radiation emission that would be detectable up to high redshift by LISA. We show that similar physical effects are important for the formation of close binary stars.Comment: 38 pages, 14 figures, submitted to Ap

Targeted Therapies for Renal Cell Carcinoma: Review of Adverse Event Management Strategies

With the advent of targeted agents for the treatment of renal cell carcinoma (RCC), overall survival has improved, and patients are being treated continuously for increasingly long periods of time. This has raised challenges in the management of adverse events (AEs) associated with the six targeted agents approved in RCC—sorafenib, sunitinib, pazopanib, bevacizumab (in combination with interferon alpha), temsirolimus, and everolimus. Suggestions for monitoring and managing AEs have been published, but there are few consensus recommendations. In addition, there is a risk that patients will be subjected to multiple unnecessary investigations. In this review, we aimed to identify the level of supporting evidence for suggested AE management strategies to provide practical guidance on essential monitoring and management that should be undertaken when using targeted agents. Five databases were systematically searched for relevant English language articles (including American Society of Clinical Oncology abstracts) published between January 2007 and March 2011; European Society of Medical Oncology congress abstracts were hand searched. Strategies for AE management were summarized and categorized according to the level of recommendation. A total of 107 articles were identified that describe a large number of different investigations for monitoring AEs and interventions for AE management. We identify and summarize clear recommendations for the management of dermatologic, gastrointestinal, thyroid, cardiovascular, and other AEs, based predominantly on expert opinion. However, because the evidence for the suggested management strategies is largely anecdotal, there is a need for further systematic investigation of management strategies for AEs related to targeted therapies for RC

Mg(2)Si(x)Sn(1-x)heterostructures on Si(111) substrate for optoelectronics and thermoelectronics

Thin (50-90 m) non-doped and doped (by Al atoms) Mg2Sn0.6Si0.4 and Mg(2)Sn(0.4)Si(0.6)films with roughness of 1.9-3.7 nm have been grown by multiple deposition and single annealing at 150 degrees C of multilayers formed by repetition deposition of three-layers (Si-Sn-Mg) on Si(111) p-type wafers with 45 cm resistivity. Transmission electron microscopy has shown that the first forming layer is an epitaxial layer of hex-Mg2Sn(300) on Si(111) substrate with thickness not more than 5-7 nm. Epitaxial relationships: hex-Mg2Sn(300)parallel to Si(111), hex-Mg2Sn[001]parallel to Si[-112] and hex-Mg2Sn[030]parallel to Si[110] have been found for the epitaxial layer. But inclusions of cub-Mg2Si were also observed inside hex-Mg2Sn layer. It was found that the remaining part of the film thickness is in amorphous state and has a layered distribution of major elements: Mg, Sn and Mg without exact chemical composition. It was established by optical spectroscopy data that both type films are semiconductor with undispersed region lower 0.18 eV with n(o) = 3.59 +/- 0.01, but only two direct interband transitions with energies 0.75-0.76 eV and 1.2 eV have been determined. The last interband transition has been confirmed by photoreflectance data at room temperature. Fourier transmittance spectroscopy and Raman spectroscopy data have established the formation of stannide, silicide and ternary compositions

Probing patchy reionization through tau-21cm correlation statistics

We consider the cross-correlation between free electrons and neutral hydrogen during the epoch of reionization (EoR). The free electrons are traced by the optical depth to reionization τ, while the neutral hydrogen can be observed through 21 cm photon emission. As expected, this correlation is sensitive to the detailed physics of reionization. Foremost, if reionization occurs through the merger of relatively large halos hosting an ionizing source, the free electrons and neutral hydrogen are anticorrelated for most of the reionization history. A positive contribution to the correlation can occur when the halos that can form an ionizing source are small. A measurement of this sign change in the cross-correlation could help disentangle the bias and the ionization history. We estimate the signal-to-noise ratio of the cross-correlation using the estimator for inhomogeneous reionization $\hat{\tau }_{\ell m}$ proposed by Dvorkin and Smith. We find that with upcoming radio interferometers and cosmic microwave background (CMB) experiments, the cross-correlation is measurable going up to multipoles ℓ ~ 1000. We also derive parameter constraints and conclude that, despite the foregrounds, the cross-correlation provides a complementary measurement of the EoR parameters to the 21 cm and CMB polarization autocorrelations expected to be observed in the coming decade.Physic