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AbstractCross-validation is applied to the choice of the parameters that control the degree of smoothing in generalized Whittaker—Henderson graduation. The approach is compared with the Bayesian method, and is illustrated by graduation of a data set of Hickman and Miller and of data underlying the English Life Table number 13 (males).

AbstractIn a quantum dot the magnetic moment, proportional to the persistent currents, is given by the derivative with respect to the magnetic field of the energy of the system, which for noninteracting electrons is just the sum of the lowest filled one-particle levels. These quantities are calculated for round and square dots, with and without interior holes, using hard wall boundary conditions. The relation is traced between the old results of Landau for a large system and what may be expected in current experiments on small quantum dots of various sizes and shapes. For the square ring geometry at low and moderate magnetic fields we note and discuss the appearance of gaps separating braids of groups of four levels.

The paper considers bone-marrow repopulation experiments with injected mixtures of two types, A and B, of genetically marked donor cells. The covariance of the proportions of type A erythrocytes and lymphocytes is analysed as the sum of two components, under a stratified binomial model allowing the proportions of type A cells to vary in postulated strata of the mixture and with the assumption that the genetic marker does not influence cell development. The ratio of the two components is not experimentally estimable, but each of them has an interesting “demographic” interpretation. Possible inferences about certain “two-cell probabilities” are derived, and the experimental findings that necessitated the stratified model are illustrated.

The concept of informativeness is introduced in the context of A. J. Clark's pioneering “concentration-action” studies, in relation to the stimulus-response function of the accepted theory of agonist/receptor reactions and their observable consequences. The dominance of so-called “null-methods” in the existing literature is noted and contrasted with an informativeness analysis in which the unknown but estimable stimulus-response function plays an explicit rôle. Some statistical advantages of the latter approach are emphasised.

Two response models of fundamental importance in pharmacology are introduced, which are partly-specified functions of experimental variables, unknown parameters and random disturbances. An analysis is carried out of the extent of determination of the parameters from knowledge of isobol structure alone, with results that are more powerful than might have been expected. Moreover, such knowledge is exhaustive, unless untestable assumptions are admitted. The paper is not concerned with statistical methods for estimating the determined parameters.

AbstractFractal dimensions of particle populations of cohesive sediment were examined during deposition experiments in an annular flume at four conditions of steady-state flow (0.058, 0.123, 0.212 and 0.323 Pa). Light microscopy and an image analysis system were used to determine area, longest axis and perimeter of suspended solids. Four fractal dimensions (D, D1, D2, Dk) were calculated from the slopes of regression lines of the relevant variables on double log plots. The fractal dimension D, which relates the projected area (A) to the perimeter (P) of the particle (P∝AD/2), increased from 1.25±0.005 at a shear stress of 0.058 Pa to a maximum of 1.36±0.003 at 0.121 Pa then decreased to 1.34±0.001 at 0.323 Pa. The change in D indicated that particle boundaries became more convoluted and the shape of larger particles was more irregular at higher levels of shear stress. At the highest shear stress, the observed decrease in D resulted from floc breakage due to increased particle collisions. The fractal dimension D1, which relates the longest axis (l) to the perimeter of the particle (P∝lD1), increased from 1.00±0.006 at a shear stress of 0.058 Pa to a maximum of 1.25±0.003 at 0.325 Pa. The fractal dimension D2, which relates the longest axis with the projected area of the particle (A∝lD2), increased from 1.35±0.014 at a shear stress of 0.058 Pa to a maximum of 1.81±0.005 at 0.323 Pa. The observed increases in D1 and D2 indicate that particles became more elongated with increasing shear stress. Values of the fractal dimension Dk, resulting from the Korcak's empirical law for particle population, decreased from 3.68±0.002 at a shear stress of 0.058 Pa to 1.33±0.001 at 0.323 Pa and indicate that the particle size distribution changed from a population of similar sized particles at low shear to larger flocculated particles at higher levels of shear. The results show that small particle clusters (micro-flocs) are the formational units of larger flocs in the water column and the stability of larger flocs is a function of the shear stress at steady state.

AbstractEpigenetic silencing and inappropriate activation of gene expression are frequent events during the initiation and progression of cancer. These events involve a complex interplay between the hypermethylation of CpG dinucleotides within gene promoter and enhancer regions, the recruitment of transcriptional corepressors and the deacetylation and/or methylation of histone tails. These epigenetic regulators act in concert to block transcription or interfere with the maintenance of chromatin boundary regions. However, DNA/histone methylation and histone acetylation states are reversible, enzyme-mediated processes and as such, have emerged as promising targets for cancer therapy. This review will focus on the potential benefits and synergistic/additive effects of combining DNA-demethylating agents and histone deacetylase inhibitors or lysine-specific demethylase inhibitors together in epigenetic therapy for solid tumors and will highlight what is known regarding the mechanisms of action that contribute to the antitumor response.

SummaryBasic principles of engineering tribology are briefly reviewed, in terms of surface metrology, contact mechanics, friction, lubrication and wear. In each of these topics, applications to artificial hip joints are discussed in detail. Various artificial hip joints with different bearing material combinations are considered, including ultra-high molecular weight polyethylene against metal or ceramic, metal-on-metal and ceramic-on-ceramic.

AbstractIn recognition that pressure equipment welds that have not undergone a full volumetric inspection may contain internal defects, a weld efficiency is introduced. For spot volumetric inspection which is typically 10% of the weld length the weld efficiency is taken as 0.85. Of interest is that this factor is universally adopted in all known pressure equipment codes around the world. Its origins are obscure and to the authors’ best knowledge, has gone unchallenged for the past 88 years. Additional interest is the use of 0.7 weld efficiency for a weld that has undergone no volumetric inspection. This is prevalent in many international pressure equipment code, but not all.This paper revisits these factors. It considers how they were developed and explores a more rigorous probabilistic approach based on the amount of volumetric inspection and the likelihood of defects. It also considers the closely associated design factors. Understanding also that weld technology has developed since the early 1900 and in particular with the introduction of new technologies such as submerged arc welding, it may not be unreasonable to expect these weld efficiencies to differ from that initially developed. While the paper is not conclusive in its findings, it highlights there is justification to question the weld efficiencies adopted and proposes a program to develop more rigorous values.

Highlights•Following suboptimal alendronate adherence, transitioning to denosumab was more effective than transitioning to risedronate as measured by BMD and sCTX-1.•Transitioning to denosumab treatment was well tolerated in these postmenopausal women.•Women suboptimally adherent to alendronate may benefit from transitioning to denosumab, a therapy with a unique mechanism of action.

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