A statistical evaluation of the fixed dose procedure

The fixed-dose procedure (FDP) was introduced as OECD Test Guideline 420 in 1992, as an alternative to the conventional median lethal dose (LD50) test for the assessment of acute oral toxicity (OECD Test Guideline 401). The FDP uses fewer animals and causes less suffering than the conventional test, while providing information on the acute toxicity to allow substances to be ranked according to the EU hazard classification system. Recently the FDP has been revised, with the aim of providing further reductions and refinements, and classification according to the criteria of the Globally Harmonized Hazard Classification and Labelling scheme (GHS). This paper describes the revised FDP and analyses its properties, as determined by a statistical modelling approach. The analysis shows that the revised FDP classifies substances for acute oral toxicity generally in the same, or a more stringent, hazard class as that based on the LD50 value, according to either the GHS or the EU classification scheme. The likelihood of achieving the same classification is greatest for substances with a steep dose-response curve and median toxic dose (TD50) close to the LD50. The revised FDP usually requires five or six animals with two or fewer dying as a result of treatment in most cases.

Some general comparative points on Chao's and Zelterman's estimators of the population size

Two simple and frequently used capture–recapture estimates of the population size are compared: Chao's lower-bound estimate and Zelterman's estimate allowing for contaminated distributions. In the Poisson case it is shown that if there are only counts of ones and twos, the estimator of Zelterman is always bounded above by Chao's estimator. If counts larger than two exist, the estimator of Zelterman is becoming larger than that of Chao's, if only the ratio of the frequencies of counts of twos and ones is small enough. A similar analysis is provided for the binomial case. For a two-component mixture of Poisson distributions the asymptotic bias of both estimators is derived and it is shown that the Zelterman estimator can experience large overestimation bias. A modified Zelterman estimator is suggested and also the bias-corrected version of Chao's estimator is considered. All four estimators are compared in a simulation study.

Metabolism of Rhizobium bacteroids

Nitrogen fixation within legume nodules results from a complex metabolic exchange between bacteria of the family Rhizobiaciae and the plant host. Carbon is supplied to the differentiated bacterial cells, termed bacteroids, in the form of dicarboxylic acids to fuel nitrogen fixation. In exchange, fixed nitrogen is transferred to the plant. Both the bacteroid and the plant-derived peribacteroid membrane tightly regulate the exchange of metabolites. In the bacteroid oxidation of dicarboxylic acids via the TCA cycle occurs in an oxygen-limited environment. This restricts the TCA cycle at key points, such as the 2-oxoglutarate dehydrogenase complex, and requires that inputs of carbon and reductant are balanced with outputs from the TCA cycle. This may be achieved by metabolism through accessory pathways that can remove intermediates, reductant, or ATP from the cycle. These include synthesis of the carbon polymers PHB and glycogen and bypass pathways such as the recently identified 2-oxoglutarate decarboxylase reaction in soybean bacteroids. Recent labeling data have shown that bacteroids synthesize and secrete amino acids, which has led to controversy over the role of amino acids in nodule metabolism. Here we review bacteroid carbon metabolism in detail, evaluate the labeling studies that relate to amino acid metabolism by bacteroids, and place the work in context with the genome sequences of Mesorhizobium loti and Sinorhizobium meliloti. We also consider a wider range of metabolic pathways that are probably of great importance to rhizobia in the rhizosphere, during nodule initiation, infection thread development, and bacteroid development.

Full-dimensional quantum calculations of ground-state tunneling splitting of malonaldehyde using an accurate ab initio potential energy surface

Quantum calculations of the ground vibrational state tunneling splitting of H-atom and D-atom transfer in malonaldehyde are performed on a full-dimensional ab initio potential energy surface (PES). The PES is a fit to 11 147 near basis-set-limit frozen-core CCSD(T) electronic energies. This surface properly describes the invariance of the potential with respect to all permutations of identical atoms. The saddle-point barrier for the H-atom transfer on the PES is 4.1 kcal/mol, in excellent agreement with the reported ab initio value. Model one-dimensional and "exact" full-dimensional calculations of the splitting for H- and D-atom transfer are done using this PES. The tunneling splittings in full dimensionality are calculated using the unbiased "fixed-node" diffusion Monte Carlo (DMC) method in Cartesian and saddle-point normal coordinates. The ground-state tunneling splitting is found to be 21.6 cm(-1) in Cartesian coordinates and 22.6 cm(-1) in normal coordinates, with an uncertainty of 2-3 cm(-1). This splitting is also calculated based on a model which makes use of the exact single-well zero-point energy (ZPE) obtained with the MULTIMODE code and DMC ZPE and this calculation gives a tunneling splitting of 21-22 cm(-1). The corresponding computed splittings for the D-atom transfer are 3.0, 3.1, and 2-3 cm(-1). These calculated tunneling splittings agree with each other to within less than the standard uncertainties obtained with the DMC method used, which are between 2 and 3 cm(-1), and agree well with the experimental values of 21.6 and 2.9 cm(-1) for the H and D transfer, respectively. (C) 2008 American Institute of Physics.

EOQ, JIT and fixed costs in the Ready-mixed concrete industry

The successful implementation of just-in-time (JIT) purchasing policy in many industries has prompted many companies that still use the economic order quantity (EOQ) purchasing policy to ponder if they should switch to the JIT purchasing policy. Despite existing studies that directly compare the costs between the EOQ and JIT purchasing systems, this decision is, however, still difficult to be made, especially when price discount has to be considered. JIT purchasing may not always be successful even though plants that adopted JIT operations have experienced or can take advantage of physical space reduction. Hence, the objective of this study is to expand on a classical EOQ with a price discount model to derive the EOQ–JIT cost indifference point. The objective was tested and achieved through a survey and case study conducted in the ready-mixed concrete industry in Singapore.

A new solution of the rendering equation with stratified Monte Carlo approach

This paper is turned to the advanced Monte Carlo methods for realistic image creation. It offers a new stratified approach for solving the rendering equation. We consider the numerical solution of the rendering equation by separation of integration domain. The hemispherical integration domain is symmetrically separated into 16 parts. First 9 sub-domains are equal size of orthogonal spherical triangles. They are symmetric each to other and grouped with a common vertex around the normal vector to the surface. The hemispherical integration domain is completed with more 8 sub-domains of equal size spherical quadrangles, also symmetric each to other. All sub-domains have fixed vertices and computable parameters. The bijections of unit square into an orthogonal spherical triangle and into a spherical quadrangle are derived and used to generate sampling points. Then, the symmetric sampling scheme is applied to generate the sampling points distributed over the hemispherical integration domain. The necessary transformations are made and the stratified Monte Carlo estimator is presented. The rate of convergence is obtained and one can see that the algorithm is of super-convergent type.

Synapsing variable-length crossover: Meaningful crossover for variable-length genomes

The synapsing variable-length crossover (SVLC algorithm provides a biologically inspired method for performing meaningful crossover between variable-length genomes. In addition to providing a rationale for variable-length crossover, it also provides a genotypic similarity metric for variable-length genomes, enabling standard niche formation techniques to be used with variable-length genomes. Unlike other variable-length crossover techniques which consider genomes to be rigid inflexible arrays and where some or all of the crossover points are randomly selected, the SVLC algorithm considers genomes to be flexible and chooses non-random crossover points based on the common parental sequence similarity. The SVLC algorithm recurrently "glues" or synapses homogenous genetic subsequences together. This is done in such a way that common parental sequences are automatically preserved in the offspring with only the genetic differences being exchanged or removed, independent of the length of such differences. In a variable-length test problem, the SVLC algorithm compares favorably with current variable-length crossover techniques. The variable-length approach is further advocated by demonstrating how a variable-length genetic algorithm (GA) can obtain a high fitness solution in fewer iterations than a traditional fixed-length GA in a two-dimensional vector approximation task.

Optimal 3D surface reconstruction from a small number of conventional 2D X-ray images

This paper describes a method for reconstructing 3D frontier points, contour generators and surfaces of anatomical objects or smooth surfaces from a small number, e. g. 10, of conventional 2D X-ray images. The X-ray images are taken at different viewing directions with full prior knowledge of the X-ray source and sensor configurations. Unlike previous works, we empirically demonstrate that if the viewing directions are uniformly distributed around the object's viewing sphere, then the reconstructed 3D points automatically cluster closely on a highly curved part of the surface and are widely spread on smooth or flat parts. The advantage of this property is that the reconstructed points along a surface or a contour generator are not under-sampled or under-represented because surfaces or contours should be sampled or represented with more densely points where their curvatures are high. The more complex the contour's shape, the greater is the number of points required, but the greater the number of points is automatically generated by the proposed method. Given that the number of viewing directions is fixed and the viewing directions are uniformly distributed, the number and distribution of the reconstructed points depend on the shape or the curvature of the surface regardless of the size of the surface or the size of the object. The technique may be used not only in medicine but also in industrial applications.

Modelling fixed plant and algal dynamics in rivers: an application to the River Frome

The development of eutrophication in river systems is poorly understood given the complex relationship between fixed plants, algae, hydrodynamics, water chemistry and solar radiation. However there is a pressing need to understand the relationship between the ecological status of rivers and the controlling environmental factors to help the reasoned implementation of the Water Framework Directive and Catchment Sensitive Farming in the UK. This research aims to create a dynamic, process-based, mathematical in-stream model to simulate the growth and competition of different vegetation types (macrophytes, phytoplankton and benthic algae) in rivers. The model, applied to the River Frome (Dorset, UK), captured well the seasonality of simulated vegetation types (suspended algae, macrophytes, epiphytes, sediment biofilm). Macrophyte results showed that local knowledge is important for explaining unusual changes in biomass. Fixed algae simulations indicated the need for the more detailed representation of various herbivorous grazer groups, however this would increase the model complexity, the number of model parameters and the required observation data to better define the model. The model results also highlighted that simulating only phytoplankton is insufficient in river systems, because the majority of the suspended algae have benthic origin in short retention time rivers. Therefore, there is a need for modelling tools that link the benthic and free-floating habitats.

Probability density estimation with tunable kernels using orthogonal forward regression

A generalized or tunable-kernel model is proposed for probability density function estimation based on an orthogonal forward regression procedure. Each stage of the density estimation process determines a tunable kernel, namely, its center vector and diagonal covariance matrix, by minimizing a leave-one-out test criterion. The kernel mixing weights of the constructed sparse density estimate are finally updated using the multiplicative nonnegative quadratic programming algorithm to ensure the nonnegative and unity constraints, and this weight-updating process additionally has the desired ability to further reduce the model size. The proposed tunable-kernel model has advantages, in terms of model generalization capability and model sparsity, over the standard fixed-kernel model that restricts kernel centers to the training data points and employs a single common kernel variance for every kernel. On the other hand, it does not optimize all the model parameters together and thus avoids the problems of high-dimensional ill-conditioned nonlinear optimization associated with the conventional finite mixture model. Several examples are included to demonstrate the ability of the proposed novel tunable-kernel model to effectively construct a very compact density estimate accurately.

Career journeys and turning points of senior female managers in small construction firms

There is under-representation of senior female managers within small construction firms in the United Kingdom. The position is denying the sector a valuable pool of labour to address acute knowledge and skill shortages. Grounded theory on the career progression of senior female managers in these firms is developed from biographical interviews. First, a turning point model which distinguishes the interplay between human agency and work/home structure is given. Second, four career development phases are identified. The career journeys are characterized by ad hoc decisions and opportunities which were not influenced by external policies aimed at improving the representation of women in construction. Third, the 'hidden', but potentially significant, contribution of women-owned small construction firms is noted. The key challenge for policy and practice is to balance these external approaches with recognition of the 'inside out' reality of the 'lived experiences' of female managers. To progress this agenda there is a need for: appropriate longitudinal statistical data to quantify the scale of senior female managers and owners of small construction firms over time; and, social construction and gendered organizational analysis research to develop a general discourse on gender difference with these firms.