The 1.1 angstrom resolution crystal structure of [Tyr(15)]EpI, a novel alpha-conotoxin from Conus episcopatus, solved by direct methods

Conotoxins are valuable probes of receptors and ion channels because of their small size and highly selective activity. alpha-Conotoxin EpI, a 16-residue peptide from the mollusk-hunting Conus episcopatus, has the amino acid sequence GCCSDPRCNMNNPDY(SO3H)C-NH2 and appears to be an extremely potent and selective inhibitor of the alpha 3 beta 2 and alpha 3 beta 4 neuronal subtypes of the nicotinic acetylcholine receptor (nAChR). The desulfated form of EpI ([Tyr(15)]EpI) has a potency and selectivity for the nAChR receptor similar to those of EpI. Here we describe the crystal structure of [Tyr(15)]EpI solved at a resolution of 1.1 Angstrom using SnB. The asymmetric unit has a total of 284 non-hydrogen atoms, making this one of the largest structures solved de novo try direct methods. The [Tyr(15)]EpI structure brings to six the number of alpha-conotoxin structures that have been determined to date. Four of these, [Tyr(15)]EpI, PnIA, PnIB, and MII, have an alpha 4/7 cysteine framework and are selective for the neuronal subtype of the nAChR. The structure of [Tyr(15)]EpI has the same backbone fold as the other alpha 4/7-conotoxin structures, supporting the notion that this conotoxin cysteine framework and spacing give rise to a conserved fold. The surface charge distribution of [Tyr(15)]EpI is similar to that of PnIA and PnIB but is likely to be different from that of MII, suggesting that [Tyr(15)]EpI and MII may have different binding modes for the same receptor subtype.

Investigations into effective methods for assessing the condition of insulation in aged power transformers

This paper investigates the effective diagnostic technique(s) for assessing the condition of insulation in aged power transformers. A number of electrical, mechanical and chemical techniques were investigated. Many of these techniques are already used by the utility engineers and two comparatively new techniques are proposed in this paper. Results showing the effectiveness of these diagnostics are presented and correlation between the techniques are also presented. Finally, merits and suitability of different techniques are discussed in this paper.

Erosion/productivity modelling of maize farming in the Philippine uplands part II: Simulation of alternative farming methods

A version of the Agricultural Production Systems Simulator (APSIM) capable of simulating the key agronomic aspects of intercropping maize between legume shrub hedgerows was described and parameterised in the first paper of this series (Nelson et al., this issue). In this paper, APSIM is used to simulate maize yields and soil erosion from traditional open-field farming and hedgerow intercropping in the Philippine uplands. Two variants of open-field farming were simulated using APSIM, continuous and fallow, for comparison with intercropping maize between leguminous shrub hedgerows. Continuous open-field maize farming was predicted to be unsustainable in the long term, while fallow open-field farming was predicted to slow productivity decline by spreading the effect of erosion over a larger cropping area. Hedgerow intercropping was predicted to reduce erosion by maintaining soil surface cover during periods of intense rainfall, contributing to sustainable production of maize in the long term. In the third paper in this series, Nelson et al. (this issue) use cost-benefit analysis to compare the economic viability of hedgerow intercropping relative to traditional open-field farming of maize in relatively inaccessible upland areas. (C) 1998 Elsevier Science Ltd. All rights reserved.

Erosion/productivity modelling of maize farming in the Philippine uplands part III: Economic analysis of alternative farming methods

Two previous papers in this series (Nelson et al., this issue) described the use of the Agricultural Production Systems Simulator (APSIM) to simulate the effect of erosion on maize yields from open-field farming and hedgerow intercropping in the Philippine uplands. In this paper, maize yields simulated with APSIM are used to compare the economic viability of intercropping maize between leguminous shrub hedgerows with that of continuous and fallow open-field farming of maize. The analysis focuses on the economic incentives of upland farmers to adopt hedgerow intercropping, discussing farmers' planning horizons, access to credit and security of land tenure, as well as maize pricing in the Philippines. Insecure land tenure has limited the planning horizons of upland farmers, and high establishment costs reduce the economic viability of hedgerow intercropping relative to continuous and fallow open-field farming in the short term, In the long term, high discount rates and share-tenancy arrangements in which landlords do not contribute to establishment costs reduce the economic viability of hedgerow intercropping relative to fallow open-field farming, (C) 1998 Elsevier Science Ltd. All rights reserved.

The cost of life expectancy and the implicit social valuation of life

A new method of estimating the economic value of life is proposed. Using cross-country data, an equation is estimated to explain life expectancy as a function of real consumption of goods and services. The associated cost function for life expectancy in terms of the prices of specific goods and services is used to estimate the cost of a reduction in age-specific mortality rates sufficient to save the life of one person. The cost of saving a life in OECD countries is as much as 1000 times that in the poorest countries. Ethical implications are discussed.

New techniques in nutritional assessment: body composition methods

New techniques in air-displacement plethysmography seem to have overcome many of the previous problems of poor reproducibility and validity. These have made body-density measurements available to a larger range of individuals, including children, elderly and sick patients who often have difficulties in being submerged underwater in hydrodensitometry systems. The BOD POD air-displacement system (BOD POD body composition system; Life Measurement Instruments, Concord, CA, USA) is more precise than hydrodensitometry, is simple and rapid to operate (approximately 1 min measurements) and the results agree closely with those of hydrodensitometry (e.g. +/-3.4% for estimation of body fat). Body line scanners employing the principles of three-dimensional photography are potentially able to measure the surface area and volume of the body and its segments even more rapidly (approximately 10 s), but the validity of the measurements needs to be established. Advances in i.r. spectroscopy and mathematical modelling for calculating the area under the curve have improved precision for measuring enrichment of (H2O)-H-2 in studies of water dilution (CV 0.1-0.9% within the range of 400-1000 mu l/l) in saliva, plasma and urine. The technique is rapid and compares closely with mass spectrometry (bias 1 (SD 2) %). Advances in bedside bioelectrical-impedance techniques are making possible potential measurements of skinfold thicknesses and limb muscle mass electronically. Preliminary results suggest that the electronic method is more reproducible (intra-and inter-individual reproducibility for measuring skinfold thicknesses) and associated with less bias (+ 12%), than anthropometry (+ 40%). In addition to these selected examples, the 'mobility' or transfer of reference methods between centres has made the distinction between reference and bedside or field techniques less distinct than in the past.

Modelling the large deformations in stratified media - the Cosserat continuum approach

Methods employing continuum approximation in describing the deformation of layered materials possess a clear advantage over explicit models, However, the conventional implicit models based on the theory of anisotropic continua suffers from certain difficulties associated with interface slip and internal instabilities. These difficulties can be remedied by considering the bending stiffness of the layers. This implies the introduction of moment (couple) stresses and internal rotations, which leads to a Cosserat-type theory. In the present model, the behaviour of the layered material is assumed to be linearly elastic; the interfaces are assumed to be elastic perfectly plastic. Conditions of slip or no slip at the interfaces are detected by a Coulomb criterion with tension cut off at zero normal stress. The theory is valid for large deformation analysis. The model is incorporated into the finite element program AFENA and validated against analytical solutions of elementary buckling problems in layered medium. A problem associated with buckling of the roof and the floor of a rectangular excavation in jointed rock mass under high horizontal in situ stresses is considered as the main application of the theory. Copyright (C) 1999 John Wiley & Sons, Ltd.

Asymmetric MRI magnet design using a hybrid numerical method

This paper describes a hybrid numerical method for the design of asymmetric magnetic resonance imaging magnet systems. The problem is formulated as a field synthesis and the desired current density on the surface of a cylinder is first calculated by solving a Fredholm equation of the first kind. Nonlinear optimization methods are then invoked to fit practical magnet coils to the desired current density. The field calculations are performed using a semi-analytical method. A new type of asymmetric magnet is proposed in this work. The asymmetric MRI magnet allows the diameter spherical imaging volume to be positioned close to one end of the magnet. The main advantages of making the magnet asymmetric include the potential to reduce the perception of claustrophobia for the patient, better access to the patient by attending physicians, and the potential for reduced peripheral nerve stimulation due to the gradient coil configuration. The results highlight that the method can be used to obtain an asymmetric MRI magnet structure and a very homogeneous magnetic field over the central imaging volume in clinical systems of approximately 1.2 m in length. Unshielded designs are the focus of this work. This method is flexible and may be applied to magnets of other geometries. (C) 1999 Academic Press.

A hybrid, inverse approach to the design of magnetic resonance imaging magnets

This paper describes a hybrid numerical method of an inverse approach to the design of compact magnetic resonance imaging magnets. The problem is formulated as a field synthesis and the desired current density on the surface of a cylinder is first calculated by solving a Fredholm equation of the first, kind. Nonlinear optimization methods are then invoked to fit practical magnet coils to the desired current density. The field calculations are performed using a semi-analytical method. The emphasis of this work is on the optimal design of short MRI magnets. Details of the hybrid numerical model are presented, and the model is used to investigate compact, symmetric MRI magnets as well as asymmetric magnets. The results highlight that the method can be used to obtain a compact MRI magnet structure and a very homogeneous magnetic field over the central imaging volume in clinical systems of approximately 1 m in length, significantly shorter than current designs. Viable asymmetric magnet designs, in which the edge of the homogeneous region is very close to one end of the magnet system are also presented. Unshielded designs are the focus of this work. This method is flexible and may be applied to magnets of other geometries. (C) 2000 American Association of Physicists in Medicine. [S0094-2405(00)00303-5].

A comparison of three therapy methods for children with different types of developmental phonological disorder

Treatment case studies of three children whose speech was characterized by non-developmental errors are described. Three therapy methods were trialed with each child: phonological contrast; core vocabulary and PROMPT. The accuracy and intelligibility of the children's connected speech improved throughout: the course of the programme. Intervention that focused on teaching a rule about the contrastive use of phonemes was most successful for a child who consistently made non-developmental errors. Children making inconsistent errors received most benefit from the core vocabulary approach that markedly enhanced consistency of production. However, once consistency was established, one child benefited from phonological contrast therapy. While the results of the study should be interpreted with caution due to the small sample size and the cumulative effects of intervention, the findings suggest that different parts of a child's phonological and phonetic system may respond to various types of treatment approaches that target different aspects of speech production. The implication drawn is that just as no single treatment approach is appropriate for all children with disordered phonology, management of some children may involve selecting and sequencing a range of different approaches.

The burden of mental disorders: a comparison of methods between the Australian burden of disease studies and the Global Burden of Disease study

The national and Victorian burden of disease studies in Australia set out to examine critically the methods used in the Global Burden of Disease study to estimate the burden of mental disorders. The main differences include the use of a different set of disability weights allowing estimates in greater detail by level of severity, adjustments for comorbidity between mental disorders, a greater number of menta I disorders measured, and model ling of substance use disorders, anxiety disorders and bipolar disorder as chronic conditions. Uniform age-weighting in the Australian studies produces considerably lower estimates of the burden due to mental disorders in comparison with age-weighted disability-adjusted life years. A lack of follow-up data on people with mental disorders who are identified in cross-sectional surveys poses the greatest challenge in determining the burden of mental disorders more accurately.

New methods for determining quasi-stationary distributions for Markov chains

We shall be concerned with the problem of determining quasi-stationary distributions for Markovian models directly from their transition rates Q. We shall present simple conditions for a mu-invariant measure m for Q to be mu-invariant for the transition function, so that if m is finite, it can be normalized to produce a quasi-stationary distribution. (C) 2000 Elsevier Science Ltd. All rights reserved.

Longitudinal research: methods for maximizing subject follow-up

Early intervention for hazardous alcohol use has been shown repeatedly to be effective in reducing alcohol consumption, limiting alcohol-related problems and improving biochemical parameters. However, in most studies the follow-up period has been 2 years or less. The current paper presents progress on a 10-year follow-up of a randomized controlled trial of early intervention. Methods used for tracing subjects and ensuring minimal refusals are detailed. The intensity of effort required to locate subjects is documented and recommendations for ensuring good follow-up rates are made. At completion of follow-up, 72.5% of the sample reviewed here and 78.2% of the total cohort had been traced. Our experiences demonstrate that long-term follow-up is feasible, given sufficient planning and persistence.