Comparative phylogeographic summary statistics for testing simultaneous vicariance

Testing for simultaneous vicariance across comparative phylogeographic data sets is a notoriously difficult problem hindered by mutational variance, the coalescent variance, and variability across pairs of sister taxa in parameters that affect genetic divergence. We simulate vicariance to characterize the behaviour of several commonly used summary statistics across a range of divergence times, and to characterize this behaviour in comparative phylogeographic datasets having multiple taxon-pairs. We found Tajima's D to be relatively uncorrelated with other summary statistics across divergence times, and using simple hypothesis testing of simultaneous vicariance given variable population sizes, we counter-intuitively found that the variance across taxon pairs in Nei and Li's net nucleotide divergence (pi(net)), a common measure of population divergence, is often inferior to using the variance in Tajima's D across taxon pairs as a test statistic to distinguish ancient simultaneous vicariance from variable vicariance histories. The opposite and more intuitive pattern is found for testing more recent simultaneous vicariance, and overall we found that depending on the timing of vicariance, one of these two test statistics can achieve high statistical power for rejecting simultaneous vicariance, given a reasonable number of intron loci (> 5 loci, 400 bp) and a range of conditions. These results suggest that components of these two composite summary statistics should be used in future simulation-based methods which can simultaneously use a pool of summary statistics to test comparative the phylogeographic hypotheses we consider here.

Predicting residue-wise contact orders in proteins by support vector regression

Background: The residue-wise contact order (RWCO) describes the sequence separations between the residues of interest and its contacting residues in a protein sequence. It is a new kind of one-dimensional protein structure that represents the extent of long-range contacts and is considered as a generalization of contact order. Together with secondary structure, accessible surface area, the B factor, and contact number, RWCO provides comprehensive and indispensable important information to reconstructing the protein three-dimensional structure from a set of one-dimensional structural properties. Accurately predicting RWCO values could have many important applications in protein three-dimensional structure prediction and protein folding rate prediction, and give deep insights into protein sequence-structure relationships. Results: We developed a novel approach to predict residue-wise contact order values in proteins based on support vector regression (SVR), starting from primary amino acid sequences. We explored seven different sequence encoding schemes to examine their effects on the prediction performance, including local sequence in the form of PSI-BLAST profiles, local sequence plus amino acid composition, local sequence plus molecular weight, local sequence plus secondary structure predicted by PSIPRED, local sequence plus molecular weight and amino acid composition, local sequence plus molecular weight and predicted secondary structure, and local sequence plus molecular weight, amino acid composition and predicted secondary structure. When using local sequences with multiple sequence alignments in the form of PSI-BLAST profiles, we could predict the RWCO distribution with a Pearson correlation coefficient (CC) between the predicted and observed RWCO values of 0.55, and root mean square error (RMSE) of 0.82, based on a well-defined dataset with 680 protein sequences. Moreover, by incorporating global features such as molecular weight and amino acid composition we could further improve the prediction performance with the CC to 0.57 and an RMSE of 0.79. In addition, combining the predicted secondary structure by PSIPRED was found to significantly improve the prediction performance and could yield the best prediction accuracy with a CC of 0.60 and RMSE of 0.78, which provided at least comparable performance compared with the other existing methods. Conclusion: The SVR method shows a prediction performance competitive with or at least comparable to the previously developed linear regression-based methods for predicting RWCO values. In contrast to support vector classification (SVC), SVR is very good at estimating the raw value profiles of the samples. The successful application of the SVR approach in this study reinforces the fact that support vector regression is a powerful tool in extracting the protein sequence-structure relationship and in estimating the protein structural profiles from amino acid sequences.

Methicillin-resistant Staphylococcus aureus genotyping using a small set of polymorphisms

The aim of this study was to identify a set of genetic polymorphisms that efficiently divides methicillin-resistant Staphylococcus aureus (MRSA) strains into groups consistent with the population structure. The rationale was that such polymorphisms could underpin rapid real-time PCR or low-density array-based methods for monitoring MRSA dissemination in a cost-effective manner. Previously, the authors devised a computerized method for identifying sets of single nucleoticle polymorphisms (SNPs) with high resolving power that are defined by multilocus sequence typing (MLST) databases, and also developed a real-time PCR method for interrogating a seven-member SNP set for genotyping S. aureus. Here, it is shown that these seven SNPs efficiently resolve the major MRSA lineages and define 27 genotypes. The SNP-based genotypes are consistent with the MRSA population structure as defined by eBURST analysis. The capacity of binary markers to improve resolution was tested using 107 diverse MRSA isolates of Australian origin that encompass nine SNP-based genotypes. The addition of the virulence-associated genes cna, pvl and bbplsdrE, and the integrated plasmids pT181, p1258 and pUB110, resolved the nine SNP-based genotypes into 21 combinatorial genotypes. Subtyping of the SCCmec locus revealed new SCCmec types and increased the number of combinatorial genotypes to 24. It was concluded that these polymorphisms provide a facile means of assigning MRSA isolates into well-recognized lineages.

Improved joint control using a genetic algorithm for a humanoid robot

This paper describes experiments conducted in order to simultaneously tune 15 joints of a humanoid robot. Two Genetic Algorithm (GA) based tuning methods were developed and compared against a hand-tuned solution. The system was tuned in order to minimise tracking error while at the same time achieve smooth joint motion. Joint smoothness is crucial for the accurate calculation of online ZMP estimation, a prerequisite for a closedloop dynamically stable humanoid walking gait. Results in both simulation and on a real robot are presented, demonstrating the superior smoothness performance of the GA based methods.

The theory of on-line learning: a statistical physics approach

In this paper we review recent theoretical approaches for analysing the dynamics of on-line learning in multilayer neural networks using methods adopted from statistical physics. The analysis is based on monitoring a set of macroscopic variables from which the generalisation error can be calculated. A closed set of dynamical equations for the macroscopic variables is derived analytically and solved numerically. The theoretical framework is then employed for defining optimal learning parameters and for analysing the incorporation of second order information into the learning process using natural gradient descent and matrix-momentum based methods. We will also briefly explain an extension of the original framework for analysing the case where training examples are sampled with repetition.

Individual and group differences in driving behaviour

Road traffic accident involvement rates show that younger males are over represented in accidents. A number of studies have shown individual differences in accident involvement. Questionnaire-based methods to investigate individual and group differences in driver stress and risk perceptions reported in chapter 2 and 3 revealed that neuroticism was associated with; heightened perception of personal risk, driver stress, and inefficient coping strategies. Younger drivers and female drivers reported higher levels of stress. Young male drivers assessed their personal risk and driving abilities less realistically than did other age and sex groups. Driving simulator-based methods reported in chapter 4 revealed that young drivers and male drivers; drive faster, overtake more often, and commit more `high risk' overtakes than do other age and sex groups. Middle-aged and elderly drivers were poorer at maintaining a fixed distance from a lead `vehicle'. Older drivers adopt a slower, more cautious driving style, but appear to be worse at controlling distance from a `lead' vehicle. Results are consistent with individual and group differences in accident involvement rates. Findings are discussed with reference to the implementation of driver education programs to reduce stress, the adoption of more realistic perceptions of risk among younger drivers, and the training of compensation strategies to counteract age-related changes in older drivers.

Computer aided geometric design of form-rolls for NC manufacture

Conventional methods of form-roll design and manufacture for Cold Roll-Forming of thin-walled metal sections have been entirely manual, time consuming and prone to errors, resulting in inefficiency and high production costs. With the use of computers, lead time can be significantly improved, particularly for those aspects involving routine but tedious human decisions and actions. This thesis describes the development of computer aided tools for producing form-roll designs for NC manufacture in the CAD/CAM environment. The work was undertaken to modernise the existing activity of a company manufacturing thin-walled sections. The investigated areas of the activity, including the design and drafting of the finished section, the flower patterns, the 10 to 1 templates, and the rolls complete with pinch-difference surfaces, side-rolls and extension-contours, have been successfully computerised by software development . Data generated by the developed software can be further processed for roll manufacturing using NC lathes. The software has been specially designed for portability to facilitate its implementation on different computers. The Opening-Radii method of forming was introduced as a subsitute to the conventional method for better forming. Most of the essential aspects in roll design have been successfully incorporated in the software. With computerisation, extensive standardisation in existing roll design practices and the use of more reliable and scientifically-based methods have been achieved. Satisfactory and beneficial results have also been obtained by the company in using the software through a terminal linked to the University by a GPO line. Both lead time and productivity in roll design and manufacture have been significantly improved. It is therefore concluded that computerisation in the design of form-rolls for automation by software development is viable. The work also demonstrated the promising nature of the CAD/CAM approach.

A combination of cyclone and vert techniques for the management of construction projects

Many planning and control tools, especially network analysis, have been developed in the last four decades. The majority of them were created in military organization to solve the problem of planning and controlling research and development projects. The original version of the network model (i.e. C.P.M/PERT) was transplanted to the construction industry without the consideration of the special nature and environment of construction projects. It suited the purpose of setting up targets and defining objectives, but it failed in satisfying the requirement of detailed planning and control at the site level. Several analytical and heuristic rules based methods were designed and combined with the structure of C.P.M. to eliminate its deficiencies. None of them provides a complete solution to the problem of resource, time and cost control. VERT was designed to deal with new ventures. It is suitable for project evaluation at the development stage. CYCLONE, on the other hand, is concerned with the design and micro-analysis of the production process. This work introduces an extensive critical review of the available planning techniques and addresses the problem of planning for site operation and control. Based on the outline of the nature of site control, this research developed a simulation based network model which combines part of the logics of both VERT and CYCLONE. Several new nodes were designed to model the availability and flow of resources, the overhead and operating cost and special nodes for evaluating time and cost. A large software package is written to handle the input, the simulation process and the output of the model. This package is designed to be used on any microcomputer using MS-DOS operating system. Data from real life projects were used to demonstrate the capability of the technique. Finally, a set of conclusions are drawn regarding the features and limitations of the proposed model, and recommendations for future work are outlined at the end of this thesis.

An iterative agent bidding mechanism for responsive manufacturing

In today's market, the global competition has put manufacturing businesses in great pressures to respond rapidly to dynamic variations in demand patterns across products and changing product mixes. To achieve substantial responsiveness, the manufacturing activities associated with production planning and control must be integrated dynamically, efficiently and cost-effectively. This paper presents an iterative agent bidding mechanism, which performs dynamic integration of process planning and production scheduling to generate optimised process plans and schedules in response to dynamic changes in the market and production environment. The iterative bidding procedure is carried out based on currency-like metrics in which all operations (e.g. machining processes) to be performed are assigned with virtual currency values, and resource agents bid for the operations if the costs incurred for performing them are lower than the currency values. The currency values are adjusted iteratively and resource agents re-bid for the operations based on the new set of currency values until the total production cost is minimised. A simulated annealing optimisation technique is employed to optimise the currency values iteratively. The feasibility of the proposed methodology has been validated using a test case and results obtained have proven the method outperforming non-agent-based methods.

On the hydrophobicity of peptides:comparing empirical predictions of peptide log P values

Peptides are of great therapeutic potential as vaccines and drugs. Knowledge of physicochemical descriptors, including the partition coefficient logP, is useful for the development of predictive Quantitative Structure-Activity Relationships (QSARs). We have investigated the accuracy of available programs for the prediction of logP values for peptides with known experimental values obtained from the literature. Eight prediction programs were tested, of which seven programs were fragment-based methods: XLogP, LogKow, PLogP, ACDLogP, AlogP, Interactive Analysis's LogP and MlogP; and one program used a whole molecule approach: QikProp. The predictive accuracy of the programs was assessed using r(2) values, with ALogP being the most effective (r( 2) = 0.822) and MLogP the least (r(2) = 0.090). We also examined three distinct types of peptide structure: blocked, unblocked, and cyclic. For each study (all peptides, blocked, unblocked and cyclic peptides) the performance of programs rated from best to worse is as follows: all peptides - ALogP, QikProp, PLogP, XLogP, IALogP, LogKow, ACDLogP, and MlogP; blocked peptides - PLogP, XLogP, ACDLogP, IALogP, LogKow, QikProp, ALogP, and MLogP; unblocked peptides - QikProp, IALogP, ALogP, ACDLogP, MLogP, XLogP, LogKow and PLogP; cyclic peptides - LogKow, ALogP, XLogP, MLogP, QikProp, ACDLogP, IALogP. In summary, all programs gave better predictions for blocked peptides, while, in general, logP values for cyclic peptides were under-predicted and those of unblocked peptides were over-predicted.

Towards in silico prediction of immunogenic epitopes

As torrents of new data now emerge from microbial genomics, bioinformatic prediction of immunogenic epitopes remains challenging but vital. In silico methods often produce paradoxically inconsistent results: good prediction rates on certain test sets but not others. The inherent complexity of immune presentation and recognition processes complicates epitope prediction. Two encouraging developments – data driven artificial intelligence sequence-based methods for epitope prediction and molecular modeling methods based on three-dimensional protein structures – offer hope for the future.

Digital Libraries and Portals Saving National Cultural Heritage (IMI–BAS Experience)

The current research activities of the Institute of Mathematics and Informatics at the Bulgarian Academy of Sciences (IMI—BAS) include the study and application of knowledge-based methods for the creation, integration and development of multimedia digital libraries with applications in cultural heritage. This report presents IMI-BAS’s developments at the digital library management systems and portals, i.e. the Bulgarian Iconographical Digital Library, the Bulgarian Folklore Digital Library and the Bulgarian Folklore Artery, etc. developed during the several national and international projects: - "Digital Libraries with Multimedia Content and its Application in Bulgarian Cultural Heritage" (contract 8/21.07.2005 between the IMI–BAS, and the State Agency for Information Technologies and Communications; - FP6/IST/P-027451 PROJECT LOGOS "Knowledge-on-Demand for Ubiquitous Learning", EU FP6, IST, Priority 2.4.13 "Strengthening the Integration of the ICT research effort in an Enlarged Europe" - NSF project D-002-189 SINUS "Semantic Technologies for Web Services and Technology Enhanced Learning". - NSF project IO-03-03/2006 ―Development of Digital Libraries and Information Portal with Virtual Exposition "Bulgarian Folklore Heritage". The presented prototypes aims to provide flexible and effective access to the multimedia presentation of the cultural heritage artefacts and collections, maintaining different forms and format of the digitized information content and rich functionality for interaction. The developments are a result of long- standing interests and work in the technological developments in information systems, knowledge processing and content management systems. The current research activities aims at creating innovative solutions for assembling multimedia digital libraries for collaborative use in specific cultural heritage context, maintaining their semantic interoperability and creating new services for dynamic aggregation of their resources, access improvement, personification, intelligent curation of content, and content protection. The investigations are directed towards the development of distributed tools for aggregating heterogeneous content and ensuring semantic compatibility with the European digital library EUROPEANA, thus providing possibilities for pan- European access to rich digitalised collections of Bulgarian cultural heritage.

When is an image a health claim? A false-recollection method to detect implicit inferences about products' health benefits

Objective: Images on food and dietary supplement packaging might lead people to infer (appropriately or inappropriately) certain health benefits of those products. Research on this issue largely involves direct questions, which could (a) elicit inferences that would not be made unprompted, and (b) fail to capture inferences made implicitly. Using a novel memory-based method, in the present research, we explored whether packaging imagery elicits health inferences without prompting, and the extent to which these inferences are made implicitly. Method: In 3 experiments, participants saw fictional product packages accompanied by written claims. Some packages contained an image that implied a health-related function (e.g., a brain), and some contained no image. Participants studied these packages and claims, and subsequently their memory for seen and unseen claims were tested. Results: When a health image was featured on a package, participants often subsequently recognized health claims that—despite being implied by the image—were not truly presented. In Experiment 2, these recognition errors persisted despite an explicit warning against treating the images as informative. In Experiment 3, these findings were replicated in a large consumer sample from 5 European countries, and with a cued-recall test. Conclusion: These findings confirm that images can act as health claims, by leading people to infer health benefits without prompting. These inferences appear often to be implicit, and could therefore be highly pervasive. The data underscore the importance of regulating imagery on product packaging; memory-based methods represent innovative ways to measure how leading (or misleading) specific images can be. (PsycINFO Database Record (c) 2016 APA, all rights reserved)

Overcoming bottlenecks in the membrane protein structural biology pipeline

Membrane proteins account for a third of the eukaryotic proteome, but are greatly under-represented in the Protein Data Bank. Unfortunately, recent technological advances in X-ray crystallography and EM cannot account for the poor solubility and stability of membrane protein samples. A limitation of conventional detergent-based methods is that detergent molecules destabilize membrane proteins, leading to their aggregation. The use of orthologues, mutants and fusion tags has helped improve protein stability, but at the expense of not working with the sequence of interest. Novel detergents such as glucose neopentyl glycol (GNG), maltose neopentyl glycol (MNG) and calixarene-based detergents can improve protein stability without compromising their solubilizing properties. Styrene maleic acid lipid particles (SMALPs) focus on retaining the native lipid bilayer of a membrane protein during purification and biophysical analysis. Overcoming bottlenecks in the membrane protein structural biology pipeline, primarily by maintaining protein stability, will facilitate the elucidation of many more membrane protein structures in the near future.

Representation of people of South Asian origin in cardiovascular outcome trials of glucose-lowering therapies in Type 2 diabetes

Aims : Our aim was to investigate the proportional representation of people of South Asian origin in cardiovascular outcome trials of glucose-lowering drugs or strategies in Type 2 diabetes, noting that these are among the most significant pieces of evidence used to formulate the guidelines on which clinical practice is largely based. Methods : We searched for cardiovascular outcome trials in Type 2 diabetes published before January 2015, and extracted data on the ethnicity of participants. These were compared against expected values for proportional representation of South Asian individuals, based on population data from the USA, from the UK, and globally. Results : Twelve studies met our inclusion criteria and, of these, eight presented a sufficiently detailed breakdown of participant ethnicity to permit numerical analysis. In general, people of South Asian origin were found to be under-represented in trials compared with UK and global expectations and over-represented compared with US expectations. Among the eight trials for which South Asian representation could be reliably estimated, seven under-represented this group relative to the 11.2% of the UK diabetes population estimated to be South Asian, with the representation in these trials ranging from 0.0% to 10.0%. Conclusions : Clinicians should exercise caution when generalizing the results of trials to their own practice, with regard to the ethnicity of individuals. Efforts should be made to improve reporting of ethnicity and improve diversity in trial recruitment, although we acknowledge that there are challenges that must be overcome to make this a reality.