hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex

hSSB1 is a newly discovered single-stranded DNA (ssDNA)-binding protein that is essential for efficient DNA double-strand break signalling through ATM. However, the mechanism by which hSSB1 functions to allow efficient signalling is unknown. Here, we show that hSSB1 is recruited rapidly to sites of double-strand DNA breaks (DSBs) in all interphase cells (G1, S and G2) independently of, CtIP, MDC1 and the MRN complex (Rad50, Mre11, NBS1). However expansion of hSSB1 from the DSB site requires the function of MRN. Strikingly, silencing of hSSB1 prevents foci formation as well as recruitment of MRN to sites of DSBs and leads to a subsequent defect in resection of DSBs as evident by defective RPA and ssDNA generation. Our data suggests that hSSB1 functions upstream of MRN to promote its recruitment at DSBs and is required for efficient resection of DSBs. These findings, together with previous work establish essential roles of hSSB1 in controlling ATM activation and activity, and subsequent DSB resection and homologous recombination (HR).

Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks

DNA double-strand break (DSB) repair via the homologous recombination pathway is a multi-stage process, which results in repair of the DSB without loss of genetic information or fidelity. One essential step in this process is the generation of extended single-stranded DNA (ssDNA) regions at the break site. This ssDNA serves to induce cell cycle checkpoints and is required for Rad51 mediated strand invasion of the sister chromatid. Here, we show that human Exonuclease 1 (Exo1) is required for the normal repair of DSBs by HR. Cells depleted of Exo1 show chromosomal instability and hypersensitivity to ionising radiation (IR) exposure. We find that Exo1 accumulates rapidly at DSBs and is required for the recruitment of RPA and Rad51 to sites of DSBs, suggesting a role for Exo1 in ssDNA generation. Interestingly, the phosphorylation of Exo1 by ATM appears to regulate the activity of Exo1 following resection, allowing optimal Rad51 loading and the completion of HR repair. These data establish a role for Exo1 in resection of DSBs in human cells, highlighting the critical requirement of Exo1 for DSB repair via HR and thus the maintenance of genomic stability.

Double standards in cultural judgements

The author, a teacher of television and film from a cultural studies perspective, endeavours to persuade his students to give up snobbery when they judge culture. The author has found that most students enter university with a series of middle class value judgements very strongly in place. Essentially, the judgements are that commercial culture is 'bad' and non-commercial culture is 'good'.

Digital broadcasting : a double edge sword in protecting children from disturbing news content

New technologies have the potential to both expose children to and protect them from television news footage likely to disturb or frighten. The advent of cheap, portable and widely available digital technology has vastly increased the possibility of violent news events being captured and potentially broadcast. This material has the potential to be particularly disturbing and harmful to young children. But on the flipside, available digital technology could be used to build in protection for young viewers especially when it comes to preserving scheduled television programming and guarding against violent content being broadcast during live crosses from known trouble spots. Based on interviews with news directors, parents and a review of published material two recommendations are put forward: 1. Digital television technology should be employed to prevent news events "overtaking" scheduled children's programming and to protect safe harbours placed in the classifications zones to protect children. 2. Broadcasters should regain control of the images that go to air during "live" feeds from obviously volatile situations by building in short delays in G classification zones.

Developing the eclectic paradigm of internationalization on the issue of multinational contractors bidding for Australian infrastructure

Against a background of already thin markets in some sectors of major public sector infrastructure in Australia and the desire of the Australian federal government to leverage private finance, concerns about ensuring sufficient levels of competition are prompting federal government to seek new sources of in-bound foreign direct income - as part of attracting more foreign contractors and consortia to bid for Australian public sector major infrastructure. As a first step towards attracting greater overseas interest in the Australian public sector market infrastructure market, an improved understanding of the determinants of multinational contractors’ willingness to bid in this market is offered by Dunning’s eclectic paradigm and which have has been a dominant approach in international business for over 20 years and yet has been little used in the context of international contracting. This paper aims to develop Dunning’s eclectic framework and also gives a brief outline of a research plan to collect secondary data and primary data from international contractors around the globe in pursuance of testing the eclectic framework.

Silylation of layered double hydroxides via an induced hydrolysis method

A series of layered double hydroxides (LDHs) based composites were synthesized by using induced hydrolysis silylation method (IHS), surfactant precursor method, in-situ coprecipitation method, and direct silylation method. Their structures, morphologies, bonding modes and thermal stabilities can be readily adjusted by changing the parameters during preparation and drying processing of the LDHs. The characterization results show that the direct silylation reaction cannot occur between the dried LDHs and 3-aminopropyltriethoxysilane (APS) in an ethanol medium. However, the condensation reaction can proceed with heating process between adsorbed APS and LDHs plates. While using wet state substrates with and without surfactant and ethanol as the solvent, the silylation process can be induced by hydrolysis of APS on the surface of LDHs plates. Surfactants improve the hydrophobicity of the LDHs during the process of nucleation and crystallization, resulting in fluffy shaped crystals; meanwhile, they occupy the surface –OH positions and leave less “free –OH” available for the silylation reaction, favoring formation of silylated products with a higher population in the hydrolyzed bidentate (T2) and tridentate (T3) bonding forms. These bonding characteristics lead to spherical aggregates and tightly bonded particles. All silylated products show higher thermal stability than those of pristine LDHs.

Empirical research in business process management : introduction to the special issue

In this editorial letter, we provide the readers of Information Systems and e-Business Management with an introduction to Business Process Management and the challenges of empirical research in this field. We then briefly describe selected examples of current research efforts in this fields and how the papers accepted for this special issue contribute to extending our body of knowledge.

Double-shock control bump design optimization using hybridized evolutionary algorithms

This study investigates the application of two advanced optimization methods for solving active flow control (AFC) device shape design problem and compares their optimization efficiency in terms of computational cost and design quality. The first optimization method uses hierarchical asynchronous parallel multi-objective evolutionary algorithm and the second uses hybridized evolutionary algorithm with Nash-Game strategies (Hybrid-Game). Both optimization methods are based on a canonical evolution strategy and incorporate the concepts of parallel computing and asynchronous evaluation. One type of AFC device named shock control bump (SCB) is considered and applied to a natural laminar flow (NLF) aerofoil. The concept of SCB is used to decelerate supersonic flow on suction/pressure side of transonic aerofoil that leads to a delay of shock occurrence. Such active flow technique reduces total drag at transonic speeds which is of special interest to commercial aircraft. Numerical results show that the Hybrid-Game helps an EA to accelerate optimization process. From the practical point of view, applying a SCB on the suction and pressure sides significantly reduces transonic total drag and improves lift-to-drag (L/D) value when compared to the baseline design.

Large-Eddy Simulation of physiological pulsatile non-newtonian flow in a channel with double constriction

Physiological pulsatile flow in a 3D model of arterial double stenosis, using the modified Power-law blood viscosity model, is investigated by applying Large Eddy Simulation (LES) technique. The computational domain has been chosen is a simple channel with biological type stenoses. The physiological pulsation is generated at the inlet of the model using the first four harmonics of the Fourier series of the physiological pressure pulse. In LES, a top-hat spatial grid-filter is applied to the Navier-Stokes equations of motion to separate the large scale flows from the subgrid scale (SGS). The large scale flows are then resolved fully while the unresolved SGS motions are modelled using the localized dynamic model. The flow Reynolds numbers which are typical of those found in human large artery are chosen in the present work. Transitions to turbulent of the pulsatile non-Newtonian along with Newtonian flow in the post stenosis are examined through the mean velocity, wall shear stress, mean streamlines as well as turbulent kinetic energy and explained physically along with the relevant medical concerns.

Bond characteristics between CFRP and steel plates in double strap joints

This paper describes a series of double strap shear tests loaded in tension to investigate the bond between CFRP sheets and steel plates. Both normal modulus (240 GPa) and high modulus (640 GPa) CFRPs were used in the test program. Strain gauges were mounted to capture the strain distribution along the CFRP length. Different failure modes were observed for joints with normal modulus CFRP and those with high modulus CFRP. The strain distribution along the CFRP length was found to be similar for the two cases. A shorter effective bond length was obtained for joints with high modulus CFRP whereas larger ultimate load carrying capacity can be achieved for joints with normal modulus CFRP when the bond length is long enough. The Hart-Smith Model was modified to predict the effective bond length and ultimate load carrying capacity of joints between the normal modulus CFRP and steel plates. The Multilayer Distribution Model developed by the authors was modified to predict the load carrying capacity of joints between the high modulus CFRP and steel plates. The predicted values agreed well with experimental ones.

Experimental and finite element analysis of a double strap joint between steel plates and normal modulus CFRP

Strengthening of steel structures using externally-bonded carbon fibre reinforced polymers ‘CFRP’ is a rapidly developing technique. This paper describes the behaviour of axially loaded flat steel plates strengthened using carbon fibre reinforced polymer sheets. Two steel plates were joined together with adhesive and followed by the application of carbon fibre sheet double strap joint with different bond lengths. The behaviour of the specimens was further investigated by using nonlinear finite element analysis to predict the failure modes and load capacity. In this study, bond failure is the dominant failure mode for normal modulus (240 GPa) CFRP bonding which closely matched the results of finite elements. The predicted ultimate loads from the FE analysis are found to be in good agreement with experimental values.