New molecular targets in radiotherapy: DNA damage signalling and repair in targeted and non-targeted cells

Ionising radiation plays a key role in therapy due to its ability to directly induce DNA damage, in particular DNA double-strand breaks leading to cell death. Cells have multiple repair pathways which attempt to maintain genomic stability. DNA repair proteins have become key targets for therapy, using small molecule inhibitors, in combination with radiation and or chemotherapeutic agents as a means of enhancing cell killing. Significant advances in our understanding of the response of cells to radiation exposures has come from the observation of non-targeted effects where cells respond via mechanisms other than those which are a direct consequence of energy-dependent DNA damage. Typical of these is bystander signalling where cells respond to the fact that their neighbours have been irradiated. Bystander cells show a DNA damage response which is distinct from directly irradiated cells. In bystander cells, ATM- and Rad3-related (ATR) protein kinase-dependent signalling in response to stalled replication forks is an early event in the DNA damage response. The ATM protein kinase is activated downstream of ATR in bystander cells. This offers the potential for differential approaches for the modulation of bystander and direct effects with repair inhibitors which may impact on the response of tumours and on the protection of normal tissues during radiotherapy. (C) 2009 Elsevier B.V. All rights reserved.

WASP-24 b: A New Transiting Close-in Hot Jupiter Orbiting a Late F-star

We report the discovery of a new transiting close-in giant planet, WASP-24 b, in a 2.341 day orbit, 0.037 AU from its F8-9 type host star. By matching the star's spectrum with theoretical models, we infer an effective temperature T eff = 6075 ± 100 K and a surface gravity of log g = 4.15 ± 0.10. A comparison of these parameters with theoretical isochrones and evolutionary mass tracks places only weak constraints on the age of the host star, which we estimate to be 3.8+1.3 –1.2 Gyr. The planetary nature of the companion was confirmed by radial velocity measurements and additional photometric observations. These data were fit simultaneously in order to determine the most probable parameter set for the system, from which we infer a planetary mass of 1.071+0.036 –0.038 M Jup and radius 1.3+0.039 –0.037 R Jup.

The Effect of Risk Sensitivity on Collaborative New Product Development in a Supply Chain

The increasing risks and costs of new product development require firms to collaborate with their supply chain partners in product management. In this paper, a supply chain model is proposed with one risk-neutral supplier and one risk-averse manufacturer. The manufacturer has an opportunity to enhance demand by developing a new product, but both the actual demand for new product and the supplier’s wholesale price are uncertain. The supplier has an incentive to share risks of new product development via an advance commitment to wholesale price for its own profit maximization. The effects of the manufacturer’s risk sensitivity on the players’ optimal strategies are analyzed and the trade-off between innovation incentives and pricing flexibility is investigated from the perspective of the supplier. The results highlight the significant role of risk sensitivity in collaborative new product development, and it is found that the manufacturer’s innovation level and retail price are always decreasing in the risk sensitivity, and the supplier prefers commitment to wholesale price only when the risk sensitivity is below a certain threshold.

The Emperor's new clothes: Eclecticism in autism treatment

Increasingly, Applied Behavior Analysis (ABA) is internationally recognised as the scientific basis for teaching and treatment in autism spectrum disorders. Yet, many governments and professionals across Europe promote an eclectic model as more child-centred and pragmatic. This paper addresses the issues of eclecticism and ABA by exploring how misinformation stands in the way of evidence-based procedures that are truly unified, practical, and child-centred.