Towards a model of non-equilibrium binding of a metal ion in a biological system

We have used a systems biology approach to address the hitherto insoluble problem of the quantitative analysis of non-equilibrium binding of aqueous metal ions by competitive ligands in heterogeneous media. To-date, the relative proportions of different metal complexes in aqueous media have only been modelled at chemical equilibrium and there are no quantitative analyses of the approach to equilibrium1. While these models have improved our understanding of how metals are used in biological systems they cannot account for the influence of kinetic factors in metal binding, transport and fate2. Here we have modelled the binding of aluminium in blood serum by the iron transport protein transferrin (Tf) as it is widely accepted that the biological fate of this non-essential metal is not adequately described by experiments, in vitro and in silico, which have consistently demonstrated that at equilibrium 90% of serum Al(III) is bound by Tf3-5. We have coined this paradox 'the blood-aluminium problem'6 and herein applied a systems biology approach which utilised well-found assumptions to pare away the complexities of the problem such that it was defined by a comparatively simple set of computational rules and, importantly, its solution assumed significant predictive capabilities. Here we show that our novel computational model successfully described the binding of Al(III) by Tf both at equilibrium and as equilibrium for AlTf was approached. The model provided an explanation of why the distribution of Al(III) in the body cannot be adequately described by its binding and transport by Tf and it highlighted the significance of kinetic in addition to thermodynamic constraints in defining the fate of metal ions in biological systems. This is the first model of non-equilibrium metal binding in a biological system and it should prove to be a valuable predictive tool in furthering our understanding of the bioinorganic chemistry of metals

An outburst of the magnetic cataclysmic variable XY Arietis observed with RXTE

We report the first observed outburst of the magnetic cataclysmic variable XY Ari. X-ray observations show a flux increase by an order of magnitude the day after the first signs of outburst. During the 5-d duration the X-ray spin pulse is greatly enhanced and the X-ray spectrum far more absorbed. We suggest that the inner disc pushes inwards during outburst, blocking the view to the lower accreting pole, breaking the symmetry present in quiescence, and so producing a large pulsation. The observations are consistent with a disc instability as the cause of the outburst, although we can't rule out alternatives. We draw parallels between our data and the UV delay and dwarf nova oscillations seen in non-magnetic dwarf novae.Comment: 10 pages, 9 figures, LaTeX, also at http://www.astro.keele.ac.uk/~ch

Genetic improvement and utilisation of indigenous tilapia in southern Africa: final technical report, December 1st 1998 to June 31st, 2002

Mozambique tilapia (Oreochromis mossambicus) is an indigenous tilapia species in southern Africa, until now the majority of genetic research has been carried out on Asian species of tilapia but this project aims to look at this African species. Those most suited to further development in aquaculture in southern Africa have now been identified. The genetic characterisation of strains has been completed. This information has aided the choice of strains for use in small scale aquaculture and for genetically male tilapia (GMT) production. They will form the basis of future strategies for further genetic improvement, and management of genetic diversity of Mozambique tilapia. The information will also contribute towards responsible management and development of genetic resources, particularly with regard to indigenous species of tilapia. Good progress has been made with the adaptation and implementation of producing the supermale fish required to produce all male offspring, resulting in faster growing populations of tilapia. The presence of the project and its associated activity has been a catalyst for a surge in interest in tilapia culture throughout southern Africa. [PDF contains 183 pages

Working in social prescribing services: A qualitative study

Purpose: Social prescribing (SP) is an emerging area of public health that has the potential to alleviate pressure on primary care by offering non-clinical solutions to health problems. Whilst there is an increasing body of literature exploring service design and impact, there is little research that focuses specifically on the SP workforce. The purpose of this paper is to explore routes into SP, worker’s experiences of the sector and potential career progression. Design/methodology/approach: For this qualitative study, semi-structured interviews were conducted with eight members of the SP workforce with varying levels of responsibility from within six different organisations in an urban/suburban area of South West England. Interviews were analysed using thematic analysis. Findings: Pathways into the sector were varied, and those without direct experience often brought transferable skills from other professions. Careers in SP were clearly rewarding, and some providers had established good support structures for staff. However, some participants were in need of additional training in areas such as collaborative working and staff management. Staff working at a more senior level – particularly in community-based organisations – seemed less well supported overall, with limited career progression. Staff in such organisations also reported working beyond contractual hours. Originality/value: This study has revealed inconsistencies between the experiences of staff in some community organisations vs those associated with larger, more established services. It has also highlighted a need for further training and capacity building in some areas. These findings may be of interest to those commissioning or funding SP services in the future

The physical origin of optical flares following GRB 110205A and the nature of the outflow

The optical emission of GRB 110205A is distinguished by two flares. In this work we examine two possible scenarios for the optical afterglow emission. In the first scenario, the first optical flare is the reverse shock emission of the main outflow and the second one is powered by the prolonged activity of central engine. We however find out that it is rather hard to interpret the late ($t>0.1$ day) afterglow data reasonably unless the GRB efficiency is very high ($\sim 0.95$). In the second scenario, the first optical flare is the low energy prompt emission and the second one is the reverse shock of the initial outflow. Within this scenario we can interpret the late afterglow emission self-consistently. The reverse shock region may be weakly magnetized and the decline of the second optical flare may be dominated by the high latitude emission, for which strong polarization evolution accompanying the quick decline is possible, as suggested by Fan et al. in 2008. Time-resolved polarimetry by RINGO2-like polarimeters will test our prediction directly.Comment: Accepted for publication in RAA,8 pages, 2 figure

Evaluation of MVCT images with skin collimation for electron treatment planning

Purpose: To evaluate the accuracy of electron beam dose calculations in MVCT images containing lead alloy masks. Method and Materials: A phantom consisting of two 30x30x5 cm3 slabs of CIRS plastic water® was imaged using kVCT (GE Lightspeed-RT) and MVCT (TomoTherapy Hi·Art). Nine MVCT scans were taken with different square masks of lead alloy (Cerrobend®, density = 9.4 g·cm-3) on top of the phantom. The masks contained square apertures of 3x3 cm2, 6x6 cm2 and 10x10 cm2 and had thicknesses of 6 mm, 8 mm and 10 mm. The same collimation was simulated in the kVCT images by creating regions-of-interest (ROI) duplicating the sizes, shapes, and density of the masks. Using the Philips Pinnacle3 treatment planning system, twelve treatment plans were created for the combination of four electron energies (6, 9, 12, and 16 MeV) and the three apertures. For each plan, the mask thickness appropriate for the electron energy was used and the dose distributions calculated using the kVCT and MVCT images were compared. In uniform dose regions dose differences were calculated; in high dose-gradient regions distances-to-agreement (DTA) were measured. Results: In the uniform dose region, the maximum differences of doses in the MVCT images from doses in the kVCT images were greater than or equal to ±5% for all but one opening and energy combination. In the high dose-gradient region, more than half of the maximum DTA values exceeded 2 mm. Analysis of the MVCT images showed that the differences were largely due to two errors. First, the presence of the masks caused distortions in the MVCT numbers such that the calculated dose in the MVCT images penetrated less deeply. Second, distortion in the shape of the image of the collimation caused the calculation algorithm to scatter excess electrons into the central axis of the beam. Conclusion: The presence of Cerrobend® masks in MVCT imaging produces distortions in the CT numbers that make electron beam dose calculations insufficiently accurate for electron beam treatment planning. Supported in part by a research agreement with TomoTherapy, Inc

Efficient Parallel Algorithm for Statistical Ion Track Simulations in Crystalline Materials

We present an efficient parallel algorithm for statistical Molecular Dynamics simulations of ion tracks in solids. The method is based on the Rare Event Enhanced Domain following Molecular Dynamics (REED-MD) algorithm, which has been successfully applied to studies of, e.g., ion implantation into crystalline semiconductor wafers. We discuss the strategies for parallelizing the method, and we settle on a host-client type polling scheme in which a multiple of asynchronous processors are continuously fed to the host, which, in turn, distributes the resulting feed-back information to the clients. This real-time feed-back consists of, e.g., cumulative damage information or statistics updates necessary for the cloning in the rare event algorithm. We finally demonstrate the algorithm for radiation effects in a nuclear oxide fuel, and we show the balanced parallel approach with high parallel efficiency in multiple processor configurations.Comment: 17 pages, seven figures, four table