Simulating Supersonic Turbulence in Magnetized Molecular Clouds

We present results of large-scale three-dimensional simulations of weakly magnetized supersonic turbulence at grid resolutions up to 1024^3 cells. Our numerical experiments are carried out with the Piecewise Parabolic Method on a Local Stencil and assume an isothermal equation of state. The turbulence is driven by a large-scale isotropic solenoidal force in a periodic computational domain and fully develops in a few flow crossing times. We then evolve the flow for a number of flow crossing times and analyze various statistical properties of the saturated turbulent state. We show that the energy transfer rate in the inertial range of scales is surprisingly close to a constant, indicating that Kolmogorov's phenomenology for incompressible turbulence can be extended to magnetized supersonic flows. We also discuss numerical dissipation effects and convergence of different turbulence diagnostics as grid resolution refines from 256^3 to 1024^3 cells.Comment: 10 pages, 3 figures, to appear in the proceedings of the DOE/SciDAC 2009 conferenc

Co-directional replication-transcription conflicts lead to replication restart

August 24, 2011Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability1, 2. To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional. Virtually all bacteria have the highly expressed ribosomal RNA genes co-directional with replication3. In bacteria, co-directional encounters seem inevitable because the rate of replication is about 10–20-fold greater than the rate of transcription. However, these encounters are generally thought to be benign2, 4, 5, 6, 7, 8, 9. Biochemical analyses indicate that head-on encounters10 are more deleterious than co-directional encounters8 and that in both situations, replication resumes without the need for any auxiliary restart proteins, at least in vitro. Here we show that in vivo, co-directional transcription can disrupt replication, leading to the involvement of replication restart proteins. We found that highly transcribed rRNA genes are hotspots for co-directional conflicts between replication and transcription in rapidly growing Bacillus subtilis cells. We observed a transcription-dependent increase in association of the replicative helicase and replication restart proteins where head-on and co-directional conflicts occur. Our results indicate that there are co-directional conflicts between replication and transcription in vivo. Furthermore, in contrast to the findings in vitro, the replication restart machinery is involved in vivo in resolving potentially deleterious encounters due to head-on and co-directional conflicts. These conflicts probably occur in many organisms and at many chromosomal locations and help to explain the presence of important auxiliary proteins involved in replication restart and in helping to clear a path along the DNA for the replisome.Biotechnology and Biological Sciences Research Council (Great Britain) (Grant BB/E006450/1)Wellcome Trust (London, England) (Grant 091968/Z/10/Z)National Institutes of Health (U.S.) (Grant GM41934)National Institutes of Health (U.S.) (Postdoctoral Fellowship GM093408)Biotechnology and Biological Sciences Research Council (Great Britain) (Sabbatical Visit

Orbitally modulated dust formation by the WC7+O5 colliding-wind binary WR140

We present high-resolution infrared (2--18 micron) images of the archetypal periodic dust-making Wolf-Rayet binary system WR140 (HD 193793) taken between 2001 and 2005, and multi-colour (J -- [19.5]) photometry observed between 1989 and 2001. The images resolve the dust cloud formed by WR140 in 2001, allowing us to track its expansion and cooling, while the photometry allows tracking the average temperature and total mass of the dust. The combination of the two datasets constrains the optical properties of the dust. The most persistent dust features, two concentrations at the ends of a `bar' of emission to the south of the star, were observed to move with constant proper motions of 324+/-8 and 243+/-7 mas/y. Longer wavelength (4.68-micron and 12.5-micron) images shows dust emission from the corresponding features from the previous (1993) periastron passage and dust-formation episode. A third persistent dust concentration to the east of the binary (the `arm') was found to have a proper motion ~ 320 mas/y. Extrapolation of the motions of the concentrations back to the binary suggests that the eastern `arm' began expansion 4--5 months earlier than those in the southern `bar', consistent with the projected rotation of the binary axis and wind-collision region (WCR) on the sky. Comparison of model dust images and the observations constrain the intervals when the WCR was producing sufficiently compressed wind for dust nucleation in the WCR, and suggests that the distribution of this material was not uniform about the axis of the WCR, but more abundant in the following edge in the orbital plane.Comment: 21 pages, 10 figures, accepted for MNRAS. A version with higher resolution figures is available at ftp://ftp.roe.ac.uk/pub/pmw/wr140dust.ps.g

Algorithmic comparisons of decaying, isothermal, supersonic turbulence

Contradicting results have been reported in the literature with respect to the performance of the numerical techniques employed for the study of supersonic turbulence. We aim at characterising the performance of different particle-based and grid-based techniques on the modelling of decaying supersonic turbulence. Four different grid codes (ENZO, FLASH, TVD, ZEUS) and three different SPH codes (GADGET, PHANTOM, VINE) are compared. We additionally analysed two calculations denoted as PHANTOM A and PHANTOM B using two different implementations of artificial viscosity. Our analysis indicates that grid codes tend to be less dissipative than SPH codes, though details of the techniques used can make large differences in both cases. For example, the Morris & Monaghan viscosity implementation for SPH results in less dissipation (PHANTOM B and VINE versus GADGET and PHANTOM A). For grid codes, using a smaller diffusion parameter leads to less dissipation, but results in a larger bottleneck effect (our ENZO versus FLASH runs). As a general result, we find that by using a similar number of resolution elements N for each spatial direction means that all codes (both grid-based and particle-based) show encouraging similarity of all statistical quantities for isotropic supersonic turbulence on spatial scales k<N/32 (all scales resolved by more than 32 grid cells), while scales smaller than that are significantly affected by the specific implementation of the algorithm for solving the equations of hydrodynamics. At comparable numerical resolution, the SPH runs were on average about ten times more computationally intensive than the grid runs, although with variations of up to a factor of ten between the different SPH runs and between the different grid runs. (abridged)Comment: accepted by A&A, 22 pages, 14 figure

Peptide Conformer Acidity Analysis of Protein Flexibility Monitored by Hydrogen Exchange†

ABSTRACT: The amide hydrogens that are exposed to solvent in the high-resolution X-ray structures of ubiquitin, FK506-binding protein, chymotrypsin inhibitor 2, and rubredoxin span a billion-fold range in hydroxide-catalyzed exchange rates which are predictable by continuum dielectric methods. To facilitate analysis of transiently accessible amides, the hydroxide-catalyzed rate constants for every backbone amide of ubiquitin were determined under near physiological conditions. With the previously reported NMR-restrained molecular dynamics ensembles of ubiquitin (PDB codes 2NR2 and 2K39) used as representations of the Boltzmann-weighted conformational distribution, nearly all of the exchange rates for the highly exposed amides were more accurately predicted than by use of the high-resolution X-ray structure. More strikingly, predictions for the amide hydrogens of the NMR relaxation-restrained ensemble that become exposed to solvent in more than one but less than half of the 144 protein conformations in this ensemble were almost as accurate. In marked contrast, the exchange rates for many of the analogous amides in the residual dipolar coupling-restrained ubiquitin ensemble are substantially overestimated, as was particularly evident for the Ile 44 to Lys 48 segment which constitutes the primary interaction site for the proteasome targeting enzymes involved in polyubiquitylation. For both ensembles, “excited state ” conformers in this active site region having markedly elevated peptide acidities are represented at a population level that is 102 to 103 abov

Preventing foot ulceration in diabetes:systematic review and meta-analyses of RCT data

Aims/hypothesis: Foot ulceration is a serious complication for people with diabetes that results in high levels of morbidity for individuals and significant costs for health and social care systems. Nineteen systematic reviews of preventative interventions have been published, but none provides a reliable numerical summary of treatment effects. The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to make the best possible use of the currently available data. Methods: We conducted a systematic review and meta-analysis of RCTs of preventative interventions for foot ulceration. OVID MEDLINE and EMBASE were searched to February 2019 and the Cochrane Central Register of Controlled Trials to October 2018. RCTs of interventions to prevent foot ulcers in people with diabetes who were free from foot ulceration at trial entry were included. Two independent reviewers read the full-text articles and extracted data. The quality of trial reporting was assessed using the Cochrane Risk of Bias tool. The primary outcome of foot ulceration was summarised using pooled relative risks in meta-analyses. Results: Twenty-two RCTs of eight interventions were eligible for analysis. One trial of digital silicone devices (RR 0.07 [95% CI 0.01, 0.55]) and meta-analyses of dermal infrared thermometry (RR 0.41 [95% CI 0.19, 0.86]), complex interventions (RR 0.59 [95% CI 0.38, 0.90], and custom-made footwear and offloading insoles (RR 0.53 [95% CI 0.33, 0.85]) showed beneficial effects for these interventions. Conclusions/interpretation: Four interventions were identified as being effective in preventing foot ulcers in people with diabetes, but uncertainty remains about what works and who is most likely to benefit