Genetic algorithms in statistical tolerancing

An important aspect in manufacturing design is the distribution of geometrical tolerances so that an assembly functions with given probability, while minimising the manufacturing cost. This requires a complex search over a multidimensional domain, much of which leads to infeasible solutions and which can have many local minima. As well, Monte-Carlo methods are often required to determine the probability that the assembly functions as designed. This paper describes a genetic algorithm for carrying out this search and successfully applies it to two specific mechanical designs, enabling comparisons of a new statistical tolerancing design method with existing methods. (C) 2003 Elsevier Ltd. All rights reserved.

Hepatic disposition and metabolite kinetics of a homologous series of diflunisal esters

The hepatic disposition and metabolite kinetics of a homologous series of diflunisal O-acyl esters (acetyl, butanoyl, pentanoyl, anti hexanoyl) were determined using a single-pass perfused in situ rat liver preparation. The experiments were conducted using 2% BSA Krebs-Henseleit buffer (pH 7.4), and perfusions were performed at 30 mL/min in each liver. O-Acyl esters of diflunisal and pregenerated diflunisal were injected separately into the portal vein. The venous outflow samples containing the esters and metabolite diflunisal were analyzed by high performance liquid chromatography (HPLC). The normalized outflow concentration-time profiles for each parent ester and the formed metabolite, diflunisal, were analyzed using statistical moments analysis and the two-compartment dispersion model. Data (presented as mean +/- standard error for triplicate experiments) was compared using ANOVA repeated measures, significance level P < 0.05. The hepatic availability (AUC'), the fraction of the injected dose recovered in the outflowing perfusate, for O-acetyldiflunisal (C2D = 0.21 +/- 0.03) was significantly lower than the other esters (0.34-0.38). However, R-N/f(u), the removal efficiency number R-N divided by the unbound fraction in perfusate f(u), which represents the removal efficiency of unbound ester by the liver, was significantly higher for the most lipophilic ester (O-hexanoyldiflunisal, C6D = 16.50 +/- 0.22) compared to the other members of the series (9.57 to 11.17). The most lipophilic ester, C6D, had the largest permeability surface area (PS) product (94.52 +/- 38.20 mt min-l g-l liver) and tissue distribution value VT (35.62 +/- 11.33 mL g(-1) liver) in this series. The MTT of these O-acyl esters of diflunisal were not significantly different from one another. However, the metabolite diflunisal MTTs tended to increase with the increase in the parent ester lipophilicity (11.41 +/- 2.19 s for C2D to 38.63 +/- 9.81 s for C6D). The two-compartment dispersion model equations adequately described the outflow profiles for the parent esters and the metabolite diflunisal formed from the O-acyl esters of diflunisal in the liver.

Effects of molecular crowding by saccharides on alpha-chymotrypsin dimerization

Given the importance of protein complexes as therapeutic targets, it is necessary to understand the physical chemistry of these interactions under the crowded conditions that exist in cells. We have used sedimentation equilibrium to quantify the enhancement of the reversible homodimerization of alpha-chymotrypsin by high concentrations of the osmolytes glucose, sucrose, and raffinose. In an attempt to rationalize the ostuolyte-mediated stabilization of the a-chymotrypsin homodimer, we have used models based on binding interactions (transfer-free energy analysis) and steric interactions (excluded volume theory) to predict the stabilization. Although transfer-free energy analysis predicts reasonably well the relatively small stabilization observed for complex formation between cytochrome c and cytochrome c peroxidase, as well as that between bobtail quail lysozyme and a monoclonal Fab fragment, it underestimates the sugar-mediated stabilization of the alpha-chymotrypsin dimer. Although predictions based on excluded volume theory overestimate the stabilization, it would seem that a major determinant in the observed stabilization of the a-chymotrypsin homodimer is the thermodynamic nonideality arising from molecular crowding by the three small sugars.

Distribution kinetics of solutes in the isolated in-situ perfused rat head using the multiple indicator dilution technique and a physiological two-barrier model

The purpose of this study was to determine the pharmacokinetics of [C-14]diclofenac, [C-14]salicylate and [H-3]clonidine using a single pass rat head perfusion preparation. The head was perfused with 3-[N-morpholino] propane-sulfonic acid-buffered Ringer's solution. Tc-99m-red blood cells and a drug were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 min. A two-barrier stochastic organ model was used to estimate the statistical moments of the solutes. Plasma, interstitial and cellular distribution volumes for the solutes ranged from 1.0 mL (diclofenac) to 1.6 mL (salicylate), 2.0 mL (diclofenac) to 4.2 mL (water) and 3.9 mL (salicylate) to 20.9 mL (diclofenac), respectively. A comparison of these volumes to water indicated some exclusion of the drugs from the interstitial space and salicylate from the cellular space. Permeability-surface area (PS) products calculated from plasma to interstitial fluid permeation clearances (CLPI) (range 0.02-0.40 mL s(-1)) and fractions of solute unbound in the perfusate were in the order: diclofenac>salicylate >clonidine>sucrose (from 41.8 to 0.10 mL s(-1)). The slow efflux of diclofenac, compared with clonidine and salicylate, may be related to its low average unbound fraction in the cells. This work accounts for the tail of disposition curves in describing pharmacokinetics in the head.

Fluorinated-plasma modification of polyetherimide films

Ultem 1000 polyetherimide films prepared by cast-evaporating technique were covered with a 1H,1H,2H-tridecafluoro-oct-1-ene (PFO) plasma-polymerized layer. The effects of the plasma exposure time on the surface composition were studied by X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and surface energy analysis. The surface topography of the plasma layer was deduced from scanning electron microscopy. The F/C ratio for plasma-polymerized PFO under the input RF power of 50 W can be as high as 1.30 for 480 s and similar to 0.4-2 at % of oxygen was detected, resulting from the reaction of long-lived radicals in the plasma polymer with atmospheric oxygen. The plasma deposition of fluorocarbon coating from plasma PFO reduces the surface energy from 46 to 18.3 mJ m(-2). (c) 2006 Wiley Periodicals, Inc.

Solicitors disciplinary hearings in Queensland 1930-2000: a statistical analysis

This article reports on the results of a study undertaken by the author together with her research assistant, Heather Green. The study collected and analysed data from all disciplinary tribunal decisions heard in Queensland since 1930 in an attempt to provide empirical information which has previously been lacking. This article will outline the main features of the disciplinary system in Queensland, describe the research methodology used in the present study and then report on some findings from the study. Reported findings include a profile of solicitors who have appeared before a disciplinary hearing, the types of matters which have attracted formal discipline and the types of orders made by the tribunal. Much of the data is then presented on a time scale so as to reveal any changes over time.

A longitudinal analysis of sex differences in bone mineral accrual in healthy 8-19-year-old boys and girls

Background: Although early in life there is little discernible difference in bone mass between boys and girls, at puberty sex differences are observed. It is uncertain if these differences represent differences in bone mass or just differences in anthropometric dimensions. Aim: The study aimed to identify whether sex independently affects bone mineral content (BMC) accrual in growing boys and girls. Three sites are investigated: total body (TB), femoral neck (FN) and lumbar spine (LS). Subjects and methods: 85 boys and 67 girls were assessed annually for seven consecutive years. BMC was assessed by dual energy X-ray absorptiometry (DXA). Biological age was defined as years from age at peak height velocity (PHV). Data were analysed using a hierarchical (random effects) modelling approach. Results: When biological age, body size and body composition were controlled, boys had statistically significantly higher TB and FN BMC at all maturity levels (p < 0.05). No independent sex differences were found at the LS (p > 0.05). Conclusion: Although a statistical significant sex effect is observed, it is less than the error of the measurement, and thus sex difference are debatable. In general, sex difference are explained by anthropometric difference

Reflections on the statistical analysis of personality and norms in war, peace, and prejudice: Are deviant minorities the problem?

The compelling quality of the Global Change simulation study (Altemeyer, 2003), in which high RWA (right-wing authoritarianism)/high SDO (social dominance orientation) individuals produced poor outcomes for the planet, rests on the inference that the link between high RWA/SDO scores and disaster in the simulation can be generalized to real environmental and social situations. However, we argue that studies of the Person × Situation interaction are biased to overestimate the role of the individual variability. When variables are operationalized, strongly normative items are excluded because they are skewed and kurtotic. This occurs both in the measurement of predictor constructs, such as RWA, and in the outcome constructs, such as prejudice and war. Analyses of normal linear statistics highlight personality variables such as RWA, which produce variance, and overlook the role of norms, which produce invariance. Where both normative and personality forces are operating, as in intergroup contexts, the linear analysis generates statistics for the sample that disproportionately reflect the behavior of the deviant, antinormative minority and direct attention away from the baseline, normative position. The implications of these findings for the link between high RWA and disaster are discussed.

Lymphoproliferative disease of the ocular adnexa: A clinical and pathologic study with statistical analysis of 69 patients

Purpose: To evaluate the clinical features, treatment, and outcomes of a cohort of patients with ocular adnexal lymphoproliferative disease classified according to the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms and to perform a robust statistical analysis of these data. Methods: Sixty-nine cases of ocular adnexal lymphoproliferative disease, seen in a tertiary referral center from 1992 to 2003, were included in the study. Lesions were classified by using the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms classification. Outcome variables included disease-specific Survival, relapse-free survival, local control, and distant control. Results: Stage IV disease at presentation, aggressive lymphoma histology, the presence of prior or concurrent systemic lymphoma at presentation, and bilateral adnexal disease were significant predictors for reduced disease-specific survival, local control, and distant control. Multivariate analysis found that aggressive histology and bilateral adnexal disease had significantly reduced disease-specific Survival. Conclusions: The typical presentation of adnexal lymphoproliferative disease is with a painless mass, swelling, or proptosis; however, pain and inflammation occurred in 20% and 30% of patients, respectively. Stage at presentation, tumor histology, primary or secondary status, and whether the process was unilateral or bilateral were significant variables for disease outcome. In this study, distant spread of lymphoma was lower in patients who received greater than 20 Gy of orbital radiotherapy.

Analysis of chaotic instabilities in a rotating body with internal energy dissipation

Melnikov's method is used to analytically predict the onset of chaotic instability in a rotating body with internal energy dissipation. The model has been found to exhibit chaotic instability when a harmonic disturbance torque is applied to the system for a range of forcing amplitude and frequency. Such a model may be considered to be representative of the dynamical behavior of a number of physical systems such as a spinning spacecraft. In spacecraft, disturbance torques may arise under malfunction of the control system, from an unbalanced rotor, from vibrations in appendages or from orbital variations. Chaotic instabilities arising from such disturbances could introduce uncertainties and irregularities into the motion of the multibody system and consequently could have disastrous effects on its intended operation. A comprehensive stability analysis is performed and regions of nonlinear behavior are identified. Subsequently, the closed form analytical solution for the unperturbed system is obtained in order to identify homoclinic orbits. Melnikov's method is then applied on the system once transformed into Hamiltonian form. The resulting analytical criterion for the onset of chaotic instability is obtained in terms of critical system parameters. The sufficient criterion is shown to be a useful predictor of the phenomenon via comparisons with numerical results. Finally, for the purposes of providing a complete, self-contained investigation of this fundamental system, the control of chaotic instability is demonstated using Lyapunov's method.

Analysis of stirred mill performance using DEM simulation: Part 1 - Media motion, energy consumption and collisional environment

Stirred mills are becoming increasingly used for fine and ultra-fine grinding. This technology is still poorly understood when used in the mineral processing context. This makes process optimisation of such devices problematic. 3D DEM simulations of the flow of grinding media in pilot scale tower mills and pin mills are carried out in order to investigate the relative performance of these stirred mills. Media flow patterns and energy absorption rates and distributions are analysed here. In the second part of this paper, coherent flow structures, equipment wear and mixing and transport efficiency are analysed. (C) 2006 Published by Elsevier Ltd.

On the statistical analysis of the GS-NS0 cell proteome: Imputation, clustering and variability testing

We have undertaken two-dimensional gel electrophoresis proteomic profiling on a series of cell lines with different recombinant antibody production rates. Due to the nature of gel-based experiments not all protein spots are detected across all samples in an experiment, and hence datasets are invariably incomplete. New approaches are therefore required for the analysis of such graduated datasets. We approached this problem in two ways. Firstly, we applied a missing value imputation technique to calculate missing data points. Secondly, we combined a singular value decomposition based hierarchical clustering with the expression variability test to identify protein spots whose expression correlates with increased antibody production. The results have shown that while imputation of missing data was a useful method to improve the statistical analysis of such data sets, this was of limited use in differentiating between the samples investigated, and highlighted a small number of candidate proteins for further investigation. (c) 2006 Elsevier B.V. All rights reserved.