Dynamics of \u3cem\u3eE. Coli\u3c/em\u3e Single Stranded DNA Binding (SSB) Protein-DNA Complexes

Single stranded DNA binding proteins (SSB) are essential to the cell as they stabilize transiently open single stranded DNA (ssDNA) intermediates, recruit appropriate DNA metabolism proteins, and coordinate fundamental processes such as replication, repair and recombination. Escherichia coli single stranded DNA binding protein (EcSSB) has long served as the prototype for the study of SSB function. The structure, functions, and DNA binding properties of EcSSB are well established: The protein is a stable homotetramer with each subunit possessing an N-terminal DNA binding core, a C-terminal protein-protein interaction tail, and an intervening intrinsically disordered linker (IDL). EcSSB wraps ssDNA in multiple DNA binding modes and can diffuse along DNA to remove secondary structures and remodel other protein-DNA complexes. This review provides an update on these features based on recent findings, with special emphasis on the functional and mechanistic relevance of the IDL and DNA binding modes

Analysis of the flowability of cohesive powders using Distinct Element Method

Computer simulations using Distinct Element Method (DEM) have been carried out to investigate the effect of cohesion on the flowability of polydisperse particulate systems. For this purpose, two assemblies with different values of surface energy and made of 3000 spheres with the mechanical properties of glass beads were considered. The analysis of the flowability of the powders is presented in terms of the unconfined yield stress as a function of strain rate for different pre-consolidation loads. For values of the surface energy of 1.0 J/m2 and strain rates lower than 6 s− 1, the unconfined yield stress does not change significantly indicating a quasi-static behaviour of the particulate assemblies during the compression process. For larger strain rates, the unconfined yield stress varies with the power index of 1.2 of the strain rate. The influence of the pre-consolidating stress on the powder behaviour has also been investigated and a flow factor was obtained from the linear relationship between the unconfined yield stress and pre-consolidation stress. The computer simulations show qualitatively a good agreement with the experimental trends on highly cohesive powder flow behaviour

Analysis of the effect of cohesion and gravity on the bulk behaviour of powders using Discrete Element Method

Computer simulations using Distinct Element Method have been carried out to analyse the bulk behaviour of a polydisperse assembly of glass beads. For this purpose an assembly made of 3000 spheres were generated to which the mechanical properties of glass beads were assigned. The system was initially compressed isotropically at a strain rate of 1 s-1 in the absence of gravity and surface energy. Once the assembly reached a packing fraction of about 0.62, the effects of cohesion and gravity on the bulk behaviour were analysed for two different cases. In the first case only gravity was applied, whilst in the second case both gravity and surface energy were acting on the particles. The evolution of the components of the stress tensor for the case in which only gravity was applied indicated that the gravity did not appreciably affect the isotropy of the system. In contrast, the system in which surface energy was introduced became anisotropic. The concept of unconfined yield stress of bulk cohesive powders was used to analyse the effect of surface energy and strain rate. For values of surface energy of 1.0 J/m2 and of strain rate lower than 1 s-1 the unconfined yield strength did not change significantly indicating a quasi-static behaviour for the compression process. However, for values of strain rates larger than 1 s-1 the unconfined yield strength increased with the strain rate, following a power law trend with an index of 1.7

PyFR: An Open Source Framework for Solving Advection-Diffusion Type Problems on Streaming Architectures using the Flux Reconstruction Approach

High-order numerical methods for unstructured grids combine the superior accuracy of high-order spectral or finite difference methods with the geometric flexibility of low-order finite volume or finite element schemes. The Flux Reconstruction (FR) approach unifies various high-order schemes for unstructured grids within a single framework. Additionally, the FR approach exhibits a significant degree of element locality, and is thus able to run efficiently on modern streaming architectures, such as Graphical Processing Units (GPUs). The aforementioned properties of FR mean it offers a promising route to performing affordable, and hence industrially relevant, scale-resolving simulations of hitherto intractable unsteady flows within the vicinity of real-world engineering geometries. In this paper we present PyFR, an open-source Python based framework for solving advection-diffusion type problems on streaming architectures using the FR approach. The framework is designed to solve a range of governing systems on mixed unstructured grids containing various element types. It is also designed to target a range of hardware platforms via use of an in-built domain specific language based on the Mako templating engine. The current release of PyFR is able to solve the compressible Euler and Navier-Stokes equations on grids of quadrilateral and triangular elements in two dimensions, and hexahedral elements in three dimensions, targeting clusters of CPUs, and NVIDIA GPUs. Results are presented for various benchmark flow problems, single-node performance is discussed, and scalability of the code is demonstrated on up to 104 NVIDIA M2090 GPUs. The software is freely available under a 3-Clause New Style BSD license (see www.pyfr.org)

Improving CMB non-Gaussianity estimators using tracers of local structure

Local non-Gaussianity causes correlations between large scale perturbation modes and the small scale power. The large-scale CMB signal has contributions from the integrated Sachs Wolfe (ISW) effect, which does not correlate with the small scale power. If this ISW contribution can be removed, the sensitivity to local non-Gaussianity is improved. Gravitational lensing and galaxy counts can be used to trace the ISW contribution; in particular we show that the CMB lensing potential is highly correlated with the ISW signal. We construct a nearly-optimal estimator for the local non-Gaussianity parameter \fnl and investigate to what extent we can use this to decrease the variance on {\fnl}. We show that the variance can be decreased by up to $20\%$ at Planck sensitivity using galaxy counts. CMB lensing is a good bias-independent ISW tracer for future more sensitive observations, though the fractional decrease in variance is small if good polarization data is also available.Comment: 8 pages, 3 figures. Comments welcom

On the joint analysis of CMB temperature and lensing-reconstruction power spectra

Gravitational lensing provides a significant source of cosmological information in modern CMB parameter analyses. It is measured in both the power spectrum and trispectrum of the temperature fluctuations. These observables are often treated as independent, although as they are both determined from the same map this is impossible. In this paper, we perform a rigorous analysis of the covariance between lensing power spectrum and trispectrum analyses. We find two dominant contributions coming from: (i) correlations between the disconnected noise bias in the trispectrum measurement and sample variance in the temperature power spectrum; and (ii) sample variance of the lenses themselves. The former is naturally removed when the dominant N0 Gaussian bias in the reconstructed deflection spectrum is dealt with via a partially data-dependent correction, as advocated elsewhere for other reasons. The remaining lens-cosmic-variance contribution is easily modeled but can safely be ignored for a Planck-like experiment, justifying treating the two observable spectra as independent. We also test simple likelihood approximations for the deflection power spectrum, finding that a Gaussian with a parameter-independent covariance performs well.Comment: 25+11 pages, 14 figure

RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light

In nature, organisms are exposed to chronic low- dose ultraviolet light ( CLUV) as opposed to the acute high doses common to laboratory experiments. Analysis of the cellular response to acute high-dose exposure has delineated the importance of direct DNA repair by the nucleotide excision repair pathway(1) and for checkpoint-induced cell cycle arrest in promoting cell survival(2). Here we examine the response of yeast cells to CLUV and identify a key role for the RAD6-RAD18-RAD5 error- free postreplication repair (RAD6 error-free PRR) pathway(3,4) in promoting cell growth and survival. We show that loss of the RAD6 error- free PRR pathway results in DNA-damage-checkpoint- induced G2 arrest in CLUV-exposed cells, whereas wild-type and nucleotide-excision-repair-deficient cells are largely unaffected. Cell cycle arrest in the absence of the RAD6 error- free PRR pathway was not caused by a repair defect or by the accumulation of ultraviolet-induced photoproducts. Notably, we observed increased replication protein A (RPA) and Rad52 - yellow fluorescent protein foci(5) in the CLUV- exposed rad18 Delta cells and demonstrated that Rad52- mediated homologous recombination is required for the viability of the rad18 Delta cells after release from CLUV- induced G2 arrest. These and other data presented suggest that, in response to environmental levels of ultraviolet exposure, the RAD6 error- free PRR pathway promotes replication of damaged templates without the generation of extensive single- stranded DNA regions. Thus, the error- free PRR pathway is specifically important during chronic low- dose ultraviolet exposure to prevent counter- productive DNA checkpoint activation and allow cells to proliferate normally