The binding site distance test score: a robust method for the assessment of predicted protein binding sites

We propose a novel method for scoring the accuracy of protein binding site predictions – the Binding-site Distance Test (BDT) score. Recently, the Matthews Correlation Coefficient (MCC) has been used to evaluate binding site predictions, both by developers of new methods and by the assessors for the community wide prediction experiment – CASP8. Whilst being a rigorous scoring method, the MCC does not take into account the actual 3D location of the predicted residues from the observed binding site. Thus, an incorrectly predicted site that is nevertheless close to the observed binding site will obtain an identical score to the same number of nonbinding residues predicted at random. The MCC is somewhat affected by the subjectivity of determining observed binding residues and the ambiguity of choosing distance cutoffs. By contrast the BDT method produces continuous scores ranging between 0 and 1, relating to the distance between the predicted and observed residues. Residues predicted close to the binding site will score higher than those more distant, providing a better reflection of the true accuracy of predictions. The CASP8 function predictions were evaluated using both the MCC and BDT methods and the scores were compared. The BDT was found to strongly correlate with the MCC scores whilst also being less susceptible to the subjectivity of defining binding residues. We therefore suggest that this new simple score is a potentially more robust method for future evaluations of protein-ligand binding site predictions.

Genetic parameters and evaluations from single- and multiple-trait analysis of dairy cow fertility and milk production

Genetic parameters and breeding values for dairy cow fertility were estimated from 62 443 lactation records. Two-trait analysis of fertility and milk yield was investigated as a method to estimate fertility breeding values when culling or selection based on milk yield in early lactation determines presence or absence of fertility observations in later lactations. Fertility traits were calving interval, intervals from calving to first service, calving to conception and first to last service, conception success to first service and number of services per conception. Milk production traits were 305-day milk, fat and protein yield. For fertility traits, range of estimates of heritability (h(2)) was 0.012 to 0.028 and of permanent environmental variance (c(2)) was 0.016 to 0.032. Genetic correlations (r(g)) among fertility traits were generally high ( > 0.70). Genetic correlations of fertility with milk production traits were unfavourable (range -0.11 to 0.46). Single and two-trait analyses of fertility were compared using the same data set. The estimates of h(2) and c(2) were similar for two types of analyses. However, there were differences between estimated breeding values and rankings for the same trait from single versus multi-trait analyses. The range for rank correlation was 0.69-0.83 for all animals in the pedigree and 0.89-0.96 for sires with more than 25 daughters. As single-trait method is biased due to selection on milk yield, a multi-trait evaluation of fertility with milk yield is recommended. (C) 2002 Elsevier Science B.V. All rights reserved.

Conceptual development of a harmonised method for tracking change and evaluating policy in the agri-environment: The Agri-environmental Footprint Index

An aggregated farm-level index, the Agri-environmental Footprint Index (AFI), based on multiple criteria methods and representing a harmonised approach to evaluation of EU agri-environmental schemes is described. The index uses a common framework for the design and evaluation of policy that can be customised to locally relevant agri-environmental issues and circumstances. Evaluation can be strictly policy-focused, or broader and more holistic in that context-relevant assessment criteria that are not necessarily considered in the evaluated policy can nevertheless be incorporated. The Index structure is flexible, and can respond to diverse local needs. The process of Index construction is interactive, engaging farmers and other relevant stakeholders in a transparent decision-making process that can ensure acceptance of the outcome, help to forge an improved understanding of local agri-environmental priorities and potentially increase awareness of the critical role of farmers in environmental management. The structure of the AFI facilitates post-evaluation analysis of relative performance in different dimensions of the agri-environment, permitting identification of current strengths and weaknesses, and enabling future improvement in policy design. Quantification of the environmental impact of agriculture beyond the stated aims of policy using an 'unweighted' form of the AFI has potential as the basis of an ongoing system of environmental audit within a specified agricultural context. (C) 2009 Elsevier Ltd. All rights reserved.

Rapid model quality assessment for protein structure predictions using the comparison of multiple models without structural alignments

MOTIVATION: The accurate prediction of the quality of 3D models is a key component of successful protein tertiary structure prediction methods. Currently, clustering or consensus based Model Quality Assessment Programs (MQAPs) are the most accurate methods for predicting 3D model quality; however they are often CPU intensive as they carry out multiple structural alignments in order to compare numerous models. In this study, we describe ModFOLDclustQ - a novel MQAP that compares 3D models of proteins without the need for CPU intensive structural alignments by utilising the Q measure for model comparisons. The ModFOLDclustQ method is benchmarked against the top established methods in terms of both accuracy and speed. In addition, the ModFOLDclustQ scores are combined with those from our older ModFOLDclust method to form a new method, ModFOLDclust2, that aims to provide increased prediction accuracy with negligible computational overhead. RESULTS: The ModFOLDclustQ method is competitive with leading clustering based MQAPs for the prediction of global model quality, yet it is up to 150 times faster than the previous version of the ModFOLDclust method at comparing models of small proteins (<60 residues) and over 5 times faster at comparing models of large proteins (>800 residues). Furthermore, a significant improvement in accuracy can be gained over the previous clustering based MQAPs by combining the scores from ModFOLDclustQ and ModFOLDclust to form the new ModFOLDclust2 method, with little impact on the overall time taken for each prediction. AVAILABILITY: The ModFOLDclustQ and ModFOLDclust2 methods are available to download from: http://www.reading.ac.uk/bioinf/downloads/ CONTACT: l.j.mcguffin@reading.ac.uk.

Intrinsic disorder prediction from the analysis of multiple protein fold recognition models

Motivation: Intrinsic protein disorder is functionally implicated in numerous biological roles and is, therefore, ubiquitous in proteins from all three kingdoms of life. Determining the disordered regions in proteins presents a challenge for experimental methods and so recently there has been much focus on the development of improved predictive methods. In this article, a novel technique for disorder prediction, called DISOclust, is described, which is based on the analysis of multiple protein fold recognition models. The DISOclust method is rigorously benchmarked against the top.ve methods from the CASP7 experiment. In addition, the optimal consensus of the tested methods is determined and the added value from each method is quantified. Results: The DISOclust method is shown to add the most value to a simple consensus of methods, even in the absence of target sequence homology to known structures. A simple consensus of methods that includes DISOclust can significantly outperform all of the previous individual methods tested.

The tagged microarray marker (TAM) method for high-throughput detection of single nucleotide and indel polymorphisms

The tagged microarray marker (TAM) method allows high-throughput differentiation between predicted alternative PCR products. Typically, the method is used as a molecular marker approach to determining the allelic states of single nucleotide polymorphisms (SNPs) or insertion-deletion (indel) alleles at genomic loci in multiple individuals. Biotin-labeled PCR products are spotted, unpurified, onto a streptavidin-coated glass slide and the alternative products are differentiated by hybridization to fluorescent detector oligonucleotides that recognize corresponding allele-specific tags on the PCR primers. The main attractions of this method are its high throughput (thousands of PCRs are analyzed per slide), flexibility of scoring (any combination, from a single marker in thousands of samples to thousands of markers in a single sample, can be analyzed) and flexibility of scale (any experimental scale, from a small lab setting up to a large project). This protocol describes an experiment involving 3,072 PCRs scored on a slide. The whole process from the start of PCR setup to receiving the data spreadsheet takes 2 d.

Search space pruning and global optimization of multiple gravity assist trajectories with deep space manoeuvres

This paper deals with the design of optimal multiple gravity assist trajectories with deep space manoeuvres. A pruning method which considers the sequential nature of the problem is presented. The method locates feasible vectors using local optimization and applies a clustering algorithm to find reduced bounding boxes which can be used in a subsequent optimization step. Since multiple local minima remain within the pruned search space, the use of a global optimization method, such as Differential Evolution, is suggested for finding solutions which are likely to be close to the global optimum. Two case studies are presented.

Clustering techniques applied to multiple-models structures

In this work a method for building multiple-model structures is presented. A clustering algorithm that uses data from the system is employed to define the architecture of the multiple-model, including the size of the region covered by each model, and the number of models. A heating ventilation and air conditioning system is used as a testbed of the proposed method.

Dimension and coverage of multiple-models structures using clustering techniques

In this work a method for building multiple-model structures is presented. A clustering algorithm that uses data from the system is employed to define the architecture of the multiple-model, including the size of the region covered by each model, and the number of models. A heating ventilation and air conditioning system is used as a testbed of the proposed method.

Modelling complex systems for project planning - A semiotics motivated method

A large and complex IT project may involve multiple organizations and be constrained within a temporal period. An organization is a system comprising of people, activities, processes, information, resources and goals. Understanding and modelling such a project and its interrelationship with relevant organizations are essential for organizational project planning. This paper introduces the problem articulation method (PAM) as a semiotic method for organizational infrastructure modelling. PAM offers a suite of techniques, which enables the articulation of the business, technical and organizational requirements, delivering an infrastructural framework to support the organization. It works by eliciting and formalizing (e. g. processes, activities, relationships, responsibilities, communications, resources, agents, dependencies and constraints) and mapping these abstractions to represent the manifestation of the "actual" organization. Many analysts forgo organizational modelling methods and use localized ad hoc and point solutions, but this is not amenable for organizational infrastructures modelling. A case study of the infrared atmospheric sounding interferometer (IASI) will be used to demonstrate the applicability of PAM, and to examine its relevancy and significance in dealing with the innovation and changes in the organizations.

Synthesis method for visible and infrared broadband spaceflight antireflection coatings

Evolutionary synthesis methods, as originally described by Dobrowolski, have been shown in previous literature to be an effective method of obtaining anti-reflection coating designs. To make this method even more effective, the combination of a good starting design, the best suited thin-film materials, a realistic optimization target function and a non-gradient optimization method are used in an algorithm written for a PC. Several broadband anti-reflection designs obtained by this new design method are given as examples of its usefulness.

Synthesis of broadband anti-reflection coatings for spaceflight infrared optics

A synthesis method is outlined for the design of broadband anti-reflection coatings for use in spaceborne infrared optics. The Golden Section optimisation routine is used to make a search, using designated non-absorptive dielectric thin film combinations, for the coating design which fulfils the required spectral requirements using the least number of layers and different materials. Three examples are given of coatings designed by this method : (I) 1µm to 12µm anti-reflection coating on Zinc Sulphide using Zinc Sulphide and Yttrium Fluoride thin film materials. (ii) 2µm to 14µm anti-reflection coating on Germanium using Germanium and Ytterbium Fluoride thin film materials. (iii) 6µm to 17µm anti-reflection coating on Germanium using Lead Telluride, Zinc Selenide and Barium Fluoride. The measured spectral performance of the manufactured 6µm to 17µm coating on Germanium is given. This is the anti-reflection coating for the germanium optics in the NASA Cassini Orbiter CIRS instrument.

The application of Prony’s method to time-domain waveform data modeling in the presence of noise

In this paper,the Prony's method is applied to the time-domain waveform data modelling in the presence of noise.The following three problems encountered in this work are studied:(1)determination of the order of waveform;(2)de-termination of numbers of multiple roots;(3)determination of the residues.The methods of solving these problems are given and simulated on the computer.Finally,an output pulse of model PG-10N signal generator and the distorted waveform obtained by transmitting the pulse above mentioned through a piece of coaxial cable are modelled,and satisfactory results are obtained.So the effectiveness of Prony's method in waveform data modelling in the presence of noise is confirmed.

3D scanning by multiple fan beam X-ray sources and sensors

*** Purpose – Computer tomography (CT) for 3D reconstruction entails a huge number of coplanar fan-beam projections for each of a large number of 2D slice images, and excessive radiation intensities and dosages. For some applications its rate of throughput is also inadequate. A technique for overcoming these limitations is outlined. *** Design methodology/approach – A novel method to reconstruct 3D surface models of objects is presented, using, typically, ten, 2D projective images. These images are generated by relative motion between this set of objects and a set of ten fanbeam X-ray sources and sensors, with their viewing axes suitably distributed in 2D angular space. *** Findings – The method entails a radiation dosage several orders of magnitude lower than CT, and requires far less computational power. Experimental results are given to illustrate the capability of the technique *** Practical implications – The substantially lower cost of the method and, more particularly, its dramatically lower irradiation make it relevant to many applications precluded by current techniques *** Originality/value – The method can be used in many applications such as aircraft hold-luggage screening, 3D industrial modelling and measurement, and it should also have important applications to medical diagnosis and surgery.

An automated calibration method for non-see-through head mounted displays

Accurate calibration of a head mounted display (HMD) is essential both for research on the visual system and for realistic interaction with virtual objects. Yet, existing calibration methods are time consuming and depend on human judgements, making them error prone, and are often limited to optical see-through HMDs. Building on our existing approach to HMD calibration Gilson et al. (2008), we show here how it is possible to calibrate a non-see-through HMD. A camera is placed inside a HMD displaying an image of a regular grid, which is captured by the camera. The HMD is then removed and the camera, which remains fixed in position, is used to capture images of a tracked calibration object in multiple positions. The centroids of the markers on the calibration object are recovered and their locations re-expressed in relation to the HMD grid. This allows established camera calibration techniques to be used to recover estimates of the HMD display's intrinsic parameters (width, height, focal length) and extrinsic parameters (optic centre and orientation of the principal ray). We calibrated a HMD in this manner and report the magnitude of the errors between real image features and reprojected features. Our calibration method produces low reprojection errors without the need for error-prone human judgements.