Prediction of HLA-DQ3.2 beta ligands: evidence of multiple registers in class II binding peptides

Motivation: While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models. Methods: We describe a structure-based prediction model for modeling peptide-DQ3.2 beta complexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2 beta receptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2 beta binding and non-binding peptides obtained from biochemical and functional studies. Results: Our model predicts DQ3.2 beta binding peptides with high accuracy [area under the receiver operating characteristic (ROC) curve A(ROC) > 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2 beta peptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders.

Effects of graphene layer size on the adsorption of fluids on graphitized thermal carbon black. A computer simulation study

The adsorption of Lennard-Jones fluids (argon and nitrogen) onto a graphitized thermal carbon black surface was studied with a Grand Canonical Monte Carlo Simulation (GCMC). The surface was assumed to be finite in length and composed of three graphene layers. When the GCMC simulation was used to describe adsorption on a graphite surface, an over-prediction of the isotherm was consistently observed in the pressure regions where the first and second layers are formed. To remove this over-prediction, surface mediation was accounted for to reduce the fluid-fluid interaction. Do and co-workers have introduced the so-called surface-mediation damping factor to correct the over-prediction for the case of a graphite surface of infinite extent, and this approach has yielded a good description of the adsorption isotherm. In this paper, the effects of the finite size of the graphene layer on the adsorption isotherm and how these would affect the extent of the surface mediation were studied. It was found that this finite-surface model provides a better description of the experimental data for graphitized thermal carbon black of high surface area (i.e. small crystallite size) while the infinite- surface model describes data for carbon black of very low surface area (i.e. large crystallite size).

What is the best size descriptor to use for pharmacokinetic studies in the obese?

The prevalence of obesity in the western world is dramatically rising, with many of these individuals requiring therapeutic intervention for a variety of disease states. Despite the growing prevalence of obesity there is a paucity of information describing how doses should be adjusted, or indeed whether they need to be adjusted, in the clinical setting. This review is aimed at identifying which descriptors of body size provide the most information about the relationship between dose and concentration in the obese. The size descriptors, weight, lean body weight, ideal body weight, body surface area, body mass index, fat-free mass, percent ideal body weight, adjusted body weight and predicted normal body weight were considered as potential size descriptors. We conducted an extensive review of the literature to identify studies that have assessed the quantitative relationship between the parameters clearance (CL) and volume of distribution (V) and these descriptors of body size. Surprisingly few studies have addressed the relationship between obesity and CL or V in a quantitative manner. Despite the lack of studies there were consistent findings: (i) most studies found total body weight to be the best descriptor of V. A further analysis of the studies that have addressed V found that total body weight or another descriptor that incorporated fat mass was the preferred descriptor for drugs that have high lipophilicity; (ii) in contrast, CL was best described by lean body mass and no apparent relationship between lipophilicity or clearance mechanism and preference for body size descriptor was found. In conclusion, no single descriptor described the influence of body size on both CL and V equally well. For drugs that are dosed chronically, and therefore CL is of primary concern, dosing for obese patients should not be based on their total weight. If a weight-based dose individualization is required then we would suggest that chronic drug dosing in the obese subject should be based on lean body weight, at least until a more robust size descriptor becomes available.

Pesticide and herbicide residues in sediments and seagrasses from the Great Barrier Reef world heritage area and Queensland coast

Pesticides and herbicides including organochlorine compounds have had extensive current and past application by Queensland's intensive coastal agriculture industry as web as for a wide range of domestic, public health and agricultural purposes in urban areas, The persistent nature of these types of compounds together with possible continued illegal use of banned organochlorine compounds raises the potential for continued long-term chronic exposure to plants and animals of the Great Barrier Reef. Sediment and seagrass samples were collected from 16 intertidal and 25 subtidal sampling sites between Torres Strait and Townsville, near Mackay and Gladstone, and in Hervey and Moreton Bays in 1997 and 1998 and analysed for pesticide and herbicide residues. Low levels of atrazine (0.1-0.3 mug kg(-1)), diuron (0.2-10.1 mug kg(-1)), lindane (0.08-0.19 mug kg(-1)), dieldrin (0.05-0.37 mug kg(-1)), DDT (0.05-0.26 mug kg(-1)), and DDE (0.05-0.26 mug kg(-1)) were detected in sediments and/or seagrasses. Contaminants were mainly detected in samples collected along the high rainfall, tropical coast between Townsville and Port Douglas and in Moreton Bay. Of the contaminants detected, the herbicide diuron is of most concern as the concentrations detected have some potential to impact local seagrass communities, (C) 2000 Elsevier Science Ltd. All rights reserved.

Monitoring the condition of savanna riparian zones in Northern Australia using high spatial resolution imagery and a field based rapid assessment method

Government agencies responsible for riparian environments are assessing the combined utility of field survey and remote sensing for mapping and monitoring indicators of riparian zone condition. The objective of this work was to compare the Tropical Rapid Appraisal of Riparian Condition (TRARC) method to a satellite image based approach. TRARC was developed for rapid assessment of the environmental condition of savanna riparian zones. The comparison assessed mapping accuracy, representativeness of TRARC assessment, cost-effectiveness, and suitability for multi-temporal analysis. Two multi-spectral QuickBird images captured in 2004 and 2005 and coincident field data covering sections of the Daly River in the Northern Territory, Australia were used in this work. Both field and image data were processed to map riparian health indicators (RHIs) including percentage canopy cover, organic litter, canopy continuity, stream bank stability, and extent of tree clearing. Spectral vegetation indices, image segmentation and supervised classification were used to produce RHI maps. QuickBird image data were used to examine if the spatial distribution of TRARC transects provided a representative sample of ground based RHI measurements. Results showed that TRARC transects were required to cover at least 3% of the study area to obtain a representative sample. The mapping accuracy and costs of the image based approach were compared to those of the ground based TRARC approach. Results proved that TRARC was more cost-effective at smaller scales (1-100km), while image based assessment becomes more feasible at regional scales (100-1000km). Finally, the ability to use both the image and field based approaches for multi-temporal analysis of RHIs was assessed. Change detection analysis demonstrated that image data can provide detailed information on gradual change, while the TRARC method was only able to identify more gross scale changes. In conclusion, results from both methods were considered to complement each other if used at appropriate spatial scales.

Superstring: A scalable service discovery protocol for the wide-area pervasive environment

Arguably, the world has become one large pervasive computing environment. Our planet is growing a digital skin of a wide array of sensors, hand-held computers, mobile phones, laptops, web services and publicly accessible web-cams. Often, these devices and services are deployed in groups, forming small communities of interacting devices. Service discovery protocols allow processes executing on each device to discover services offered by other devices within the community. These communities can be linked together to form a wide-area pervasive environment, allowing processes in one p u p tu interact with services in another. However, the costs of communication and the protocols by which this communication is mediated in the wide-area differ from those of intra-group, or local-area, communication. Communication is an expensive operation for small, battery powered devices, but it is less expensive for servem and workstations, which have a constant power supply and 81'e connected to high bandwidth networks. This paper introduces Superstring, a peer to-peer service discovery protocol optimised fur use in the wide-area. Its goals are to minimise computation and memory overhead in the face of large numbers of resources. It achieves this memory and computation scalability by distributing the storage cost of service descriptions and the computation cost of queries over multiple resolvers.