Efficient and cost-effective experimental determination of kinetic constants and data: the success of a Bayesian systematic approach to drug transport, receptor binding, continuous culture and cell transport kinetics

Details about the parameters of kinetic systems are crucial for progress in both medical and industrial research, including drug development, clinical diagnosis and biotechnology applications. Such details must be collected by a series of kinetic experiments and investigations. The correct design of the experiment is essential to collecting data suitable for analysis, modelling and deriving the correct information. We have developed a systematic and iterative Bayesian method and sets of rules for the design of enzyme kinetic experiments. Our method selects the optimum design to collect data suitable for accurate modelling and analysis and minimises the error in the parameters estimated. The rules select features of the design such as the substrate range and the number of measurements. We show here that this method can be directly applied to the study of other important kinetic systems, including drug transport, receptor binding, microbial culture and cell transport kinetics. It is possible to reduce the errors in the estimated parameters and, most importantly, increase the efficiency and cost-effectiveness by reducing the necessary amount of experiments and data points measured. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Kinetic modeling of the generation of 2-and 3-methylbutanal in a heated extract of beef liver

Quantitative control of aroma generation during the Maillard reaction presents great scientific and industrial interest. Although there have been many studies conducted in simplified model systems, the results are difficult to apply to complex food systems, where the presence of other components can have a significant impact. In this work, an aqueous extract of defatted beef liver was chosen as a simplified food matrix for studying the kinetics of the Mallard reaction. Aliquots of the extract were heated under different time and temperature conditions and analyzed for sugars, amino acids, and methylbutanals, which are important Maillard-derived aroma compounds formed in cooked meat. Multiresponse kinetic modeling, based on a simplified mechanistic pathway, gave a good fit with the experimental data, but only when additional steps were introduced to take into account the interactions of glucose and glucose-derived intermediates with protein and other amino compounds. This emphasizes the significant role of the food matrix in controlling the Maillard reaction.

Knowledge-elicitation and data-mining: fusing human and industrial plant information

Knowledge-elicitation is a common technique used to produce rules about the operation of a plant from the knowledge that is available from human expertise. Similarly, data-mining is becoming a popular technique to extract rules from the data available from the operation of a plant. In the work reported here knowledge was required to enable the supervisory control of an aluminium hot strip mill by the determination of mill set-points. A method was developed to fuse knowledge-elicitation and data-mining to incorporate the best aspects of each technique, whilst avoiding known problems. Utilisation of the knowledge was through an expert system, which determined schedules of set-points and provided information to human operators. The results show that the method proposed in this paper was effective in producing rules for the on-line control of a complex industrial process. (C) 2005 Elsevier Ltd. All rights reserved.

The eMinerals Collaboratory: Tools and Experience

Collaboratories provide an environment where researchers at distant locations work together at tackling important scientific and industrial problems. In this paper we outline the tools and principles used to form the eMinerals collaboratory, and discuss the experience, from within, of working towards establishing the eMinerals project team as a functioning virtual organisation. Much of the emphasis of this paper is on experience with the IT tools. We introduce a new application sharing tool.

On the nature and cause of Specific Language Impairment: a view from sentence processing and infant research

This paper addresses the nature and cause of Specific Language Impairment (SLI) by reviewing recent research in sentence processing of children with SLI compared to typically developing (TD) children and research in infant speech perception. These studies have revealed that children with SLI are sensitive to syntactic, semantic, and real-world information, but do not show sensitivity to grammatical morphemes with low phonetic saliency, and they show longer reaction times than age-matched controls. TD children from the age of 4 show trace reactivation, but some children with SLI fail to show this effect, which resembles the pattern of adults and TD children with low working memory. Finally, findings from the German Language Development (GLAD) Project have revealed that a group of children at risk for SLI had a history of an auditory delay and impaired processing of prosodic information in the first months of their life, which is not detectable later in life. Although this is a single project that needs to be replicated with a larger group of children, it provides preliminary support for accounts of SLI which make an explicit link between an early deficit in the processing of phonology and later language deficits, and the Computational Complexity Hypothesis that argues that the language deficit in children with SLI lies in difficulties integrating different types of information at the interfaces.

Carbon balance of UK peatlands: current state of knowledge and future research challenges

The retention of peatland carbon (C) and the ability to continue to draw down and store C from the atmosphere is not only important for the UK terrestrial carbon inventory, but also for a range of ecosystem services, the landscape value and the ecology and hydrology of ~15% of the land area of the UK. Here we review the current state of knowledge on the C balance of UK peatlands using several studies which highlight not only the importance of making good flux measurements, but also the spatial and temporal variability of different flux terms that characterise a landscape affected by a range of natural and anthropogenic processes and threats. Our data emphasise the importance of measuring (or accurately estimating) all components of the peatland C budget. We highlight the role of the aquatic pathway and suggest that fluxes are higher than previously thought. We also compare the contemporary C balance of several UK peatlands with historical rates of C accumulation measured using peat cores, thus providing a long-term context for present-day measurements and their natural year-on-year variability. Contemporary measurements from 2 sites suggest that current accumulation rates (–56 to –72 g C m–2 yr–1) are at the lower end of those seen over the last 150 yr in peat cores (–35 to –209 g C m–2 yr–1). Finally, we highlight significant current gaps in knowledge and identify where levels of uncertainty are high, as well as emphasise the research challenges that need to be addressed if we are to improve the measurement and prediction of change in the peatland C balance over future decades.