Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics.

Time-varying price discovery in the eighteenth century: empirical evidence from the London and Amsterdam stock markets

This paper examines the time-varying nature of price discovery in eighteenth century cross-listed stocks. Specifically, we investigate how quickly news is reflected in prices for two of the great moneyed com- panies, the Bank of England and the East India Company, over the period 1723 to 1794. These British companies were cross-listed on the London and Amsterdam stock exchange and news between the capitals flowed mainly via the use of boats that transported mail. We examine in detail the historical context sur- rounding the defining events of the period, and use these as a guide to how the data should be analysed. We show that both trading venues contributed to price discovery, and although the London venue was more important for these stocks, its importance varies over time.

Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors

Measurements of affinity and efficacy are fundamental for work on agonists both in drug discovery and in basic studies on receptors. In this review I wish to consider methods for measuring affinity and efficacy at G protein coupled receptors (GPCRs). Agonist affinity may be estimated in terms of the dissociation constant for agonist binding to a receptor using ligand binding or functional assays. It has, however, been suggested that measurements of affinity are always contaminated by efficacy so that it is impossible to separate the two parameters. Here I show that for many GPCRs, if receptor/G protein coupling is suppressed, experimental measurements of agonist affinity using ligand binding (K-obs) provide quite accurate measures of the agonist microscopic dissociation constant (K-A). Also in pharmacological functional studies, good estimates of agonist dissociation constants are possible. Efficacy can be quantitated in several ways based on functional data ( maximal effect of the agonist (E-max), ratio of agonist dissociation constant to concentration of agonist giving half maximal effect in functional assay ( K-obs/ EC50), a combined parameter EmaxKobs/EC50). Here I show that EmaxKobs/EC50 provides the best assessment of efficacy for a range of agonists across the full range of efficacy for full to partial agonists. Considerable evidence now suggests that ligand efficacy may be dependent on the pathway used to assess it. The efficacy of a ligand may, therefore, be multidimensional. It is still, however, necessary to have accurate measures of efficacy in different pathways.

Ontological modelling of content management and provision

Information provision to address the changing requirements can be best supported by content management. The Current information technology enables information to be stored and provided from various distributed sources. To identify and retrieve relevant information requires effective mechanisms for information discovery and assembly. This paper presents a method, which enables the design of such mechanisms, with a set of techniques for articulating and profiling users' requirements, formulating information provision specifications, realising management of information content in repositories, and facilitating response to the user's requirements dynamically during the process of knowledge construction. These functions are represented in an ontology which integrates the capability of the mechanisms. The ontological modelling in this paper has adopted semiotics principles with embedded norms to ensure coherent course of actions represented in these mechanisms. (C) 2008 Elsevier B.V. All rights reserved.

Plug-and-play remote portlet publishing

Web Services for Remote Portlets (WSRP) is gaining attention among portal developers and vendors to enable easy development, increased richness in functionality, pluggability, and flexibility of deployment. Whilst currently not supporting all WSRP functionalities, open-source portal frameworks could in future use WSRP Consumers to access remote portlets found from a WSRP Producer registry service. This implies that we need a central registry for the remote portlets and a more expressive WSRP Consumer interface to implement the remote portlet functions. This paper reports on an investigation into a new system architecture, which includes a Web Services repository, registry, and client interface. The Web Services repository holds portlets as remote resource producers. A new data structure for expressing remote portlets is found and published by populating a Universal Description, Discovery and Integration (UDDI) registry. A remote portlet publish and search engine for UDDI has also been developed. Finally, a remote portlet client interface was developed as a Web application. The client interface supports remote portlet features, as well as window status and mode functions. Copyright (c) 2007 John Wiley & Sons, Ltd.

Purification and functional characterisation of rhiminopeptidase A, a novel aminopeptidase from the venom of Bitis gabonica rhinoceros

This study describes the discovery and characterisation of a novel aminopeptidase A from the venom of B. g. rhinoceros and highlights its potential biological importance. Similar to mammalian aminopeptidases, rhiminopeptidase A might be capable of playing roles in altering the blood pressure and brain function of victims. Furthermore, it could have additional effects on the biological functions of other host proteins by cleaving their N-terminal amino acids. This study points towards the importance of complete analysis of individual components of snake venom in order to develop effective therapies for snake bites.

Building a biodiversity GRID

In the BiodiversityWorld project we are building a GRID to support scientific biodiversity-related research. The requirements associated with such a GRID are somewhat different from other GRIDs, and this has influenced the architecture that we have developed. In this paper we outline these requirements, most notably the need to interoperate over a diverse set of legacy databases and applications in an environment that supports effective resource discovery and use of these resources in complex workflows. Our architecture provides an invocation model that is usable over a wide range of resource types and underlying GRID middleware. However, there is a trade-off between the flexibility provided by our architecture and its performance. We discuss how this affects the inclusion of computationally intensive applications and applications that are highly interactive; we also consider the broader issue of interoperation with other GRIDs.

Relating computer tasks to existing knowledge to improve accessibility for older adults

Routine computer tasks are often difficult for older adult computer users to learn and remember. People tend to learn new tasks by relating new concepts to existing knowledge. However, even for 'basic' computer tasks there is little, if any, existing knowledge on which older adults can base their learning. This paper investigates a custom file management interface that was designed to aid discovery and learnability by providing interface objects that are familiar to the user. A study was conducted which examined the differences between older and younger computer users when undertaking routine file management tasks using the standard Windows desktop as compared with the custom interface. Results showed that older adult computer users requested help more than ten times as often as younger users when using a standard windows/mouse configuration, made more mistakes and also required significantly more confirmations than younger users. The custom interface showed improvements over standard Windows/mouse, with fewer confirmations and less help being required. Hence, there is potential for an interface that closely mimics the real world to improve computer accessibility for older adults, aiding self-discovery and learnability.

Data management for the ocean sciences - perspectives for the next decade

There is remarkable agreement in expectations today for vastly improved ocean data management a decade from now -- capabilities that will help to bring significant benefits to ocean research and to society. Advancing data management to such a degree, however, will require cultural and policy changes that are slow to effect. The technological foundations upon which data management systems are built are certain to continue advancing rapidly in parallel. These considerations argue for adopting attitudes of pragmatism and realism when planning data management strategies. In this paper we adopt those attitudes as we outline opportunities for progress in ocean data management. We begin with a synopsis of expectations for integrated ocean data management a decade from now. We discuss factors that should be considered by those evaluating candidate “standards”. We highlight challenges and opportunities in a number of technical areas, including “Web 2.0” applications, data modeling, data discovery and metadata, real-time operational data, archival of data, biological data management and satellite data management. We discuss the importance of investments in the development of software toolkits to accelerate progress. We conclude the paper by recommending a few specific, short term targets for implementation, that we believe to be both significant and achievable, and calling for action by community leadership to effect these advancements.

Highly accurate detection of ovarian cancer using CA125 but limited improvement with serum matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling

Objectives: Our objective was to test the performance of CA125 in classifying serum samples from a cohort of malignant and benign ovarian cancers and age-matched healthy controls and to assess whether combining information from matrix-assisted laser desorption/ionization (MALDI) time-of-flight profiling could improve diagnostic performance. Materials and Methods: Serum samples from women with ovarian neoplasms and healthy volunteers were subjected to CA125 assay and MALDI time-of-flight mass spectrometry (MS) profiling. Models were built from training data sets using discriminatory MALDI MS peaks in combination with CA125 values and tested their ability to classify blinded test samples. These were compared with models using CA125 threshold levels from 193 patients with ovarian cancer, 290 with benign neoplasm, and 2236 postmenopausal healthy controls. Results: Using a CA125 cutoff of 30 U/mL, an overall sensitivity of 94.8% (96.6% specificity) was obtained when comparing malignancies versus healthy postmenopausal controls, whereas a cutoff of 65 U/mL provided a sensitivity of 83.9% (99.6% specificity). High classification accuracies were obtained for early-stage cancers (93.5% sensitivity). Reasons for high accuracies include recruitment bias, restriction to postmenopausal women, and inclusion of only primary invasive epithelial ovarian cancer cases. The combination of MS profiling information with CA125 did not significantly improve the specificity/accuracy compared with classifications on the basis of CA125 alone. Conclusions: We report unexpectedly good performance of serum CA125 using threshold classification in discriminating healthy controls and women with benign masses from those with invasive ovarian cancer. This highlights the dependence of diagnostic tests on the characteristics of the study population and the crucial need for authors to provide sufficient relevant details to allow comparison. Our study also shows that MS profiling information adds little to diagnostic accuracy. This finding is in contrast with other reports and shows the limitations of serum MS profiling for biomarker discovery and as a diagnostic tool

Phylogenies reveal predictive power of traditional medicine in bioprospecting

There is controversy about whether traditional medicine can guide drug discovery, and investment in ethnobotanically led research has fluctuated. One view is that traditionally used plants are not necessarily efficacious and there are no robust methods for distinguishing the ones that are most likely to be bioactive when selecting species for further testing. Here, we reconstruct a genus-level molecular phylogeny representing the 20,000 species found in the floras of three disparate biodiversity hotspots: Nepal, New Zealand and the Cape of South Africa. Borrowing phylogenetic methods from community ecology, we reveal significant clustering of the 1,500 traditionally used species, and provide a direct measure of the relatedness of the three medicinal floras. We demonstrate shared phylogenetic patterns across the floras: related plants from these regions are used to treat medical conditions in the same therapeutic areas. This strongly suggests independent discovery of plant efficacy, an interpretation corroborated by the presence of a significantly greater proportion of known bioactive species in these plant groups than in a random sample. Phylogenetic cross-cultural comparison can focus screening efforts on a subset of traditionally used plants that are richer in bioactive compounds, and could revitalise the use of traditional knowledge in bioprospecting.