An extensible automated protein annotation tool: standardizing input and output using validated XML

Motivation: There is a frequent need to apply a large range of local or remote prediction and annotation tools to one or more sequences. We have created a tool able to dispatch one or more sequences to assorted services by defining a consistent XML format for data and annotations. Results: By analyzing annotation tools, we have determined that annotations can be described using one or more of the six forms of data: numeric or textual annotation of residues, domains (residue ranges) or whole sequences. With this in mind, XML DTDs have been designed to store the input and output of any server. Plug-in wrappers to a number of services have been written which are called from a master script. The resulting APATML is then formatted for display in HTML. Alternatively further tools may be written to perform post-analysis.

Conservation strategy maps: a tool to facilitate biodiversity action planning illustrated using the heath fritillary butterfly

1. The UK Biodiversity Action Plan (UKBAP) identifies invertebrate species in danger of national extinction. For many of these species, targets for recovery specify the number of populations that should exist by a specific future date but offer no procedure to plan strategically to achieve the target for any species. 2. Here we describe techniques based upon geographic information systems (GIS) that produce conservation strategy maps (CSM) to assist with achieving recovery targets based on all available and relevant information. 3. The heath fritillary Mellicta athalia is a UKBAP species used here to illustrate the use of CSM. A phase 1 habitat survey was used to identify habitat polygons across the county of Kent, UK. These were systematically filtered using relevant habitat, botanical and autecological data to identify seven types of polygon, including those with extant colonies or in the vicinity of extant colonies, areas managed for conservation but without colonies, and polygons that had the appropriate habitat structure and may therefore be suitable for reintroduction. 4. Five clusters of polygons of interest were found across the study area. The CSM of two of them are illustrated here: the Blean Wood complex, which contains the existing colonies of heath fritillary in Kent, and the Orlestone Forest complex, which offers opportunities for reintroduction. 5. Synthesis and applications. Although the CSM concept is illustrated here for the UK, we suggest that CSM could be part of species conservation programmes throughout the world. CSM are dynamic and should be stored in electronic format, preferably on the world-wide web, so that they can be easily viewed and updated. CSM can be used to illustrate opportunities and to develop strategies with scientists and non-scientists, enabling the engagement of all communities in a conservation programme. CSM for different years can be presented to illustrate the progress of a plan or to provide continuous feedback on how a field scenario develops.

Mapping antimalarial pharmacophores as a useful tool for the rapid discovery of drugs effective in vivo: design, construction, characterization, and pharmacology of metaquine

Resistant strains of Plasmodium falciparum and the unavailability of useful antimalarial vaccines reinforce the need to develop new efficacious antimalarials. This study details a pharmacophore model that has been used to identify a potent, soluble, orally bioavailable antimalarial bisquinoline, metaquine (N,N'-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (dihydrochloride), which is active against Plasmodium berghei in vivo (oral ID50 of 25 mu mol/kg) and multidrug-resistant Plasmodium falciparum K1 in vitro (0.17 mu M). Metaquine shows strong affinity for the putative antimalarial receptor, heme at pH 7.4 in aqueous DMSO. Both crystallographic analyses and quantum mechanical calculations (HF/6-31+G*) reveal important regions of protonation and bonding thought to persist at parasitic vacuolar pH concordant with our receptor model. Formation of drug-heme adduct in solution was confirmed using high-resolution positive ion electrospray mass spectrometry. Metaquine showed strong binding with the receptor in a 1: 1 ratio (log K = 5.7 +/- 0.1) that was predicted by molecular mechanics calculations. This study illustrates a rational multidisciplinary approach for the development of new 4-aminoquinoline antimalarials, with efficacy superior to chloroquine, based on the use of a pharmacophore model.

Modelling metal cutting using modern ductile fracture mechanics: Quantitative explanations for some longstanding problems

The assumption that negligible work is involved in the formation of new surfaces in the machining of ductile metals, is re-examined in the light of both current Finite Element Method (FEM) simulations of cutting and modern ductile fracture mechanics. The work associated with separation criteria in FEM models is shown to be in the kJ/m2 range rather than the few J/m2 of the surface energy (surface tension) employed by Shaw in his pioneering study of 1954 following which consideration of surface work has been omitted from analyses of metal cutting. The much greater values of surface specific work are not surprising in terms of ductile fracture mechanics where kJ/m2 values of fracture toughness are typical of the ductile metals involved in machining studies. This paper shows that when even the simple Ernst–Merchant analysis is generalised to include significant surface work, many of the experimental observations for which traditional ‘plasticity and friction only’ analyses seem to have no quantitative explanation, are now given meaning. In particular, the primary shear plane angle φ becomes material-dependent. The experimental increase of φ up to a saturated level, as the uncut chip thickness is increased, is predicted. The positive intercepts found in plots of cutting force vs. depth of cut, and in plots of force resolved along the primary shear plane vs. area of shear plane, are shown to be measures of the specific surface work. It is demonstrated that neglect of these intercepts in cutting analyses is the reason why anomalously high values of shear yield stress are derived at those very small uncut chip thicknesses at which the so-called size effect becomes evident. The material toughness/strength ratio, combined with the depth of cut to form a non-dimensional parameter, is shown to control ductile cutting mechanics. The toughness/strength ratio of a given material will change with rate, temperature, and thermomechanical treatment and the influence of such changes, together with changes in depth of cut, on the character of machining is discussed. Strength or hardness alone is insufficient to describe machining. The failure of the Ernst–Merchant theory seems less to do with problems of uniqueness and the validity of minimum work, and more to do with the problem not being properly posed. The new analysis compares favourably and consistently with the wide body of experimental results available in the literature. Why considerable progress in the understanding of metal cutting has been achieved without reference to significant surface work is also discussed.

Fracture toughness and cutting

An exploratory model for cutting is presented which incorporates fracture toughness as well as the commonly considered effects of plasticity and friction. The periodic load fluctuations Been in cutting force dynamometer tests are predicted, and considerations of chatter and surface finish follow. A non-dimensional group is put forward to classify different regimes of material response to machining. It leads to tentative explanations for the difficulties of cutting materials such as ceramics and brittlo polymers, and also relates to the formation of discontinuous chips. Experiments on a range of solids with widely varying toughness/strength ratios generally agree with the analysis.

Toughness & oblique metalcutting

The implications of whether new surfaces in cutting are formed just by plastic flow past the tool or by some fracturelike separation process involving significant surface work, are discussed. Oblique metalcutting is investigated using the ideas contained in a new algebraic model for the orthogonal machining of metals (Atkins, A. G., 2003, "Modeling Metalcutting Using Modern Ductile Fracture Mechanics: Quantitative Explanations for Some Longstanding Problems," Int. J. Mech. Sci., 45, pp. 373–396) in which significant surface work (ductile fracture toughnesses) is incorporated. The model is able to predict explicit material-dependent primary shear plane angles and provides explanations for a variety of well-known effects in cutting, such as the reduction of at small uncut chip thicknesses; the quasilinear plots of cutting force versus depth of cut; the existence of a positive force intercept in such plots; why, in the size-effect regime of machining, anomalously high values of yield stress are determined; and why finite element method simulations of cutting have to employ a "separation criterion" at the tool tip. Predictions from the new analysis for oblique cutting (including an investigation of Stabler's rule for the relation between the chip flow velocity angle C and the angle of blade inclination i) compare consistently and favorably with experimental results.

Cutting, by 'pressing and slicing,' of thin floppy slices of materials illustrated by experiments on cheddar cheese and salami

Why it is easier to cut with even the sharpest knife when 'pressing down and sliding' than when merely 'pressing down alone' is explained. A variety of cases of cutting where the blade and workpiece have different relative motions is analysed and it is shown that the greater the 'slice/push ratio' xi given by ( blade speed parallel to the cutting edge/blade speed perpendicular to the cutting edge), the lower the cutting forces. However, friction limits the reductions attainable at the highest.. The analysis is applied to the geometry of a wheel cutting device (delicatessan slicer) and experiments with a cheddar cheese and a salami using such an instrumented device confirm the general predictions. (C) 2004 Kluwer Academic Publishers.

Learning from risks: A tool for post-project risk assessment

Risk management (RM) comprises of risk identification, risk analysis, response planning, monitoring and action planning tasks that are carried out throughout the life cycle of a project in order to ensure that project objectives are met. Although the methodological aspects of RM are well-defined, the philosophical background is rather vague. In this paper, a learning-based approach is proposed. In order to implement this approach in practice, a tool has been developed to facilitate construction of a lessons learned database that contains risk-related information and risk assessment throughout the life cycle of a project. The tool is tested on a real construction project. The case study findings demonstrate that it can be used for storing as well as updating risk-related information and finally, carrying out a post-project appraisal. The major weaknesses of the tool are identified as, subjectivity of the risk rating process and unwillingness of people to enter information about reasons of failure.

Development of a quantitative tool for the comparison of the prebiotic effect of dietary oligosaccharides

Aims: To develop a quantitative equation [prebiotic index ( PI)] to aid the analysis of prebiotic fermentation of commercially available and novel prebiotic carbohydrates in vitro, using previously published fermentation data. Methods: The PI equation is based on the changes in key bacterial groups during fermentation. The bacterial groups incorporated into this PI equation were bifidobacteria, lactobacilli, clostridia and bacteroides. The changes in these bacterial groups from previous studies were entered into the PI equation in order to determine a quantitative PI score. PI scores were than compared with the qualitative conclusions made in these publications. In general the PI scores agreed with the qualitative conclusions drawn and provided a quantitative measure. Conclusions: The PI allows the magnitude of prebiotic effects to be quantified rather than evaluations being solely qualitative. Significance and Impact of the Study: The PI equation may be of great use in quantifying prebiotic effects in vitro. It is expected that this will facilitate more rational food product development and the development of more potent prebiotics with activity at lower doses.