The measurement and modelling of the mechanical properties of human skin in vivo--I. The measurement

The mechanical properties of human skin in vivo are studied by means of uniaxial strain measurements. In order to obtain a stress-strain relationship which is independent of the in vivo measuring configuration, values for the effective width and effective length of the loaded skin strip have to be known. By variation of tab width and tab distance in a few series of experiments on the same subject, these effective values are found. In order to obtain a time independent stress-strain relationship a correction procedure is introduced. In this procedure the time dependent (viscoelastic) effects are described and subtracted from the total response.     

Osmotic deformation of red blood cell ghosts induced by carbohydrates

The osmotic response of bovine red blood cell ghosts to a series of sugars is studied by light scattering. The sealed and right-side-out ghosts are prepared by the procedure of Steck and Kant (Steck, T.L. and Kant, J.A. (1974) Methods Enzymol. 31, 172–180), swollen in a hypotonic phosphate-buffered saline solution and their size and shape determined by elastic and quasielastic light scattering. Different carbohydrates are then added to the suspending medium in order to examine the osmotic responses, and the osmotic deformation of ghosts is shown to be spherically symmetric. Having thus established the deformation behavior, we then rank the osmotic activity of a carbohydrate relative to a standard, i.e., raffinose. It is found that the osmotic response of the ghosts to sucrose is about the same as that to raffinose, and the response to the smaller carbohydrates simply follows the number of carbons in various sugars; glucose and fractose are about 1.7 times less effective than raffinose, and pentaerythritol and meso-erythritol are 2.3 times less effective. Glyceraldehyde, which is 3.6 times less effective than raffinose, is the least effective sugar analog among those that we have tested.     

Effective Sizes for Subdivided Populations

Many derivations of effective population sizes have been suggested in the literature; however, few account for the breeding structure and none can readily be expanded to subdivided populations. Breeding structures influence gene correlations through their effects on the number of breeding individuals of each sex, the mean number of progeny per female, and the variance in the number of progeny produced by males and females. Additionally, hierarchical structuring in a population is determined by the number of breeding groups and the migration rates of males and females among such groups. This study derives analytical solutions for effective sizes that can be applied to subdivided populations. Parameters that encapsulate breeding structure and subdivision are utilized to derive the traditional inbreeding and variance effective sizes. Also, it is shown that effective sizes can be determined for any hierarchical level of population structure for which gene correlations can accrue. Derivations of effective sizes for the accumulation of gene correlations within breeding groups (coancestral effective size) and among breeding groups (intergroup effective size) are given. The results converge to traditional, single population measures when similar assumptions are applied. In particular, inbreeding and intergroup effective sizes are shown to be special cases of the coancestral effective size, and intergroup and variance effective sizes will be equal if the population census remains constant. Instantaneous solutions for effective sizes, at any time after gene correlation begins to accrue, are given in terms of traditional F statistics or transition equations. All effective sizes are shown to converge upon a common asymptotic value when breeding tactics and migration rates are constant. The asymptotic effective size can be expressed in terms of the fixation indices and the number of breeding groups; however, the rate of approach to the asymptote is dependent upon dispersal rates. For accurate assessment of effective sizes, initial, instantaneous or asymptotic, the expressions must be applied at the lowest levels at which migration among breeding groups is nonrandom. Thus, the expressions may be applicable to lineages within socially structured populations, fragmented populations (if random exchange of genes prevails within each population), or combinations of intra- and interpopulation discontinuities of gene flow. Failure to recognize internal structures of populations may lead to considerable overestimates of inbreeding effective size, while usually underestimating variance effective size.     

The effective number of a population that varies cyclically in size. I. Discrete generations

We consider a dioecious population having numbers of males and females that vary over time in cycles of length k. It is shown that if k is small in comparison with the numbers of males and females in any generation of the cycle, the effective population number (or size), N(e), is approximately equal to the harmonic mean of the effective population sizes during any given cycle. This result holds whether the locus under consideration is autosomal or sex-linked and whether inbreeding effective population numbers or variance effective population numbers are involved in the calculation of N(e). If, however, only two successive generations in the cycle are considered and the population changes in size between these generations, the inbreeding effective population number, N(eI), differs from the variance effective population number, N(eV). The mutation effective population number turns out to be the same as the number derived using calculations involving probabilities of identity by descent. It is also shown that, at least in one special case, the eigenvalue effective population number is the same as N(eV).     

Effective population size of a population with stochastically varying size

For a Wright–Fisher model with mutation whose population size fluctuates stochastically from generation to generation, a heterozygosity effective population size is defined by means of the equilibrium average heterozygosity of the population. It is shown that this effective population size is equal to the harmonic mean of population size if and only if the stochastic changes of population size are uncorrelated. The effective population size is larger (resp. smaller) than the harmonic mean when the stochastic changes of population size are positively (resp. negatively) autocorrelated. These results and those obtained so far for other stochastic models with fluctuating population size suggest that the property that effective population sizes are always larger than the harmonic mean under the fluctuation of population size holds only for continuous time models such as diffusion and coalescent models, whereas effective population sizes can be equal to or smaller than the harmonic mean for discrete time models.     

Genetic drift and estimation of effective population size

The statistical properties of the standardized variance of gene frequency changes (a quantity equivalent to Wright's inbreeding coefficient) in a random mating population are studied, and new formulae for estimating the effective population size are developed. The accuracy of the formulae depends on the ratio of sample size to effective size, the number of generations involved (t), and the number of loci or alleles used. It is shown that the standardized variance approximately follows the chi(2) distribution unless t is very large, and the confidence interval of the estimate of effective size can be obtained by using this property. Application of the formulae to data from an isolated population of Dacus oleae has shown that the effective size of this population is about one tenth of the minimum census size, though there was a possibility that the procedure of sampling genes was improper.     

Effective size and F-statistics of subdivided populations for sex-linked loci.

For a population subdivided into an arbitrary number (s) of subpopulations, each consisting of different numbers of separate sexes, with arbitrary distributions of family size and variable migration rates by males (dm) and females (df), the recurrence equations for inbreeding coefficient and coancestry between individuals within and among subpopulations for a sex-linked locus are derived and the corresponding expressions for asymptotic effective size are obtained by solving the recurrence equations. The usual assumptions are made which are stable population size and structure, discrete generations, the island migration model, and without mutation and selection. The results show that population structure has an important effect on the inbreeding coefficients in any generation, asymptotic effective size, and F-statistics. Gene exchange among subpopulations inhibits inbreeding in initial generations but increases inbreeding in later generations. The larger the migration rate, the greater the final inbreeding coefficients and the smaller the effective size. Thus if the inbreeding coefficient is to be restricted to a specific value within a given number of generations, the appropriate population structure (the values of s, dm, and df) can be obtained by using the recurrence equations. It is shown that the greater the extent of subdivision (large s, small dm and df), the larger the effective size. For a given subdivided population, the effective size for a sex-linked locus may be larger or smaller than that for an autosomal locus, depending on the sex ratio, variance and covariance of family size, and the extend of subdivision. For the special case of a single unsubdivided population, our recurrence equations for inbreeding coefficient and coancestry and formulas for effective size reduce to the simple expressions derived by previous authors.     

No genetic evidence of sex-biased dispersal in a lekking bird, the capercaillie (Tetrao urogallus)

Sex-biased dispersal is often connected to the mating behaviour of the species. Even if patterns of natal dispersal are reasonably well documented for monogamous birds, only a few data are available for polygynous and especially lekking species. We investigated the dispersal of the capercaillie (Tetrao urogallus) by examining sex-specific gene flow among the leks. Genetic information was extracted using nuclear and mitochondrial molecular markers for sexed faecal samples and analysed by novel Bayesian statistical methods. Contrary to the traditional view that the males are highly philopatric and female is the dispersing sex, we found roughly equivalent gross and effective dispersal of the sexes. The level of polygamy has a strong influence on the effective population size and on the effective dispersal. The results do not support the theories that dispersal evolves solely as a result of resource competition or other advantages to males obtained through kin selection in lekking species.     

食品纤溶酶研究概况

溶栓疗法是血栓性疾病安全有效的治疗手段,开发安全高效、廉价的新型纤溶酶对于预防与治疗血栓性疾病具有重要意义。近年来,在许多亚洲传统发酵食品中如日本纳豆、韩国大豆酱、中国豆豉、发酵虾酱等中均发现有丰富的纤溶酶资源。本文重点介绍传统发酵食品中纤溶酶的研究概况及其开发前景。     

Some approaches to the activation of antitumor resistance mechanisms and functional analogs in the categories of synergetics

The methods for activating antitumor resistance mechanisms that were developed using the concept of the periodic system of general nonspecific adaptational reactions of the body are briefly reviewed. The principles that allow effective impacts with electromagnetic radiation and biologically active substances are described. The criteria and concepts of the theory of adaptational reactions are compared to some of the concepts and categories of synergetics. The specific features in the dynamics of the studied parameters that are induced by effective impacts are considered. The antistress nature of the systemic effect that is caused by ferromagnetic nanoparticles on animals with grafted tumors is shown. Possible mechanisms that underlie the regression of large tumors that is caused by two different factors, viz., modulated electromagnetic radiation and magnetite nanoparticles, are discussed. The cases where the order parameter changed with the development of antistress unresponsiveness and regression of experimental tumors caused by a combined electromagnetic exposure are analyzed.     

Effective Dielectric Constant of Plasmonic Nanofluid Containing Core-Shell Nanoparticles

This paper focuses on the effective dielectric constant of water-based plasmonic nanofluid containing SiO₂/Ag core/shell nanoparticles (NPs). Two effective models, based on S-parameter retrieval method and Maxwell-Garnett effective medium theory, are employed. The effective dielectric constants predicted by the two effective models are compared and the applicability is evaluated by comparing the reflectance and absorptance. Three influence factors, including volume fraction, core-shell ratio, and size of NPs, are considered. Results show both of the two effective models can predict reliable effective dielectric constants when the volume fraction, size, and core-shell ratio of nanoparticles are 5%, 25 nm, and 4:1 respectively. Only small deviations appear in the resonant region under this condition. With the increase of volume fraction, shell proportion, or size, deviations in the resonant region become larger for both of the two effective models. Therefore, the predicted effective dielectric constants are not suitable for the prediction of optical properties, because the resonant region is the key region of the solar conversion for plasmonic nanofluids. Hence, the parameters of NPs need to be changed to make the effective models applicable. Moreover, the effective model based on S-parameter retrieval can predict more reliable dielectric constant than the effective model based on Maxwell-Garnett theory.

     

An estimate of anisotropic poroelastic constants of an osteon

The anisotropic poroelastic constants of an osteon are estimated by micromechanical analysis. Two extreme cases are examined, the drained and the undrained elastic constants. The drained elastic constants are the porous medium’s effective elastic constants when the fluid in the pores easily escapes and the pore fluid can sustain no pore pressure. The undrained elastic constants are the porous medium’s effective elastic constants when the medium is fully saturated with pore fluid and the fluid cannot escape. The drained and undrained elastic constants at the lacunar and canalicular porosity tissue levels are estimated by using an effective moduli model consisting of the periodic distribution of ellipsoidal cavities. These estimated anisotropic poroelastic constants provide a database for the development of an accurate anisotropic poroelastic model of an osteon.     

Transport diffusivities of fluids in nanopores by non-equilibrium molecular dynamics simulation

We present a method to study fluid transport through nanoporous materials using highly efficient non-equilibrium molecular dynamics simulations. A steady flow is induced by applying an external field to the fluid particles within a small slab of the simulation cell. The external field generates a density gradient between both sides of the porous material, which in turn triggers a convective flux through the porous medium. The heat dissipated by the fluid flow is released by a Gaussian thermostat applied to the wall particles. This method is effective for studying diffusivities in a slit pore as well as more natural, complex wall geometries. The dependence of the diffusive flux on the external field sheds light on the transport diffusivities and allows a direct calculation of effective diffusivities. Both pore and fluid particle interactions are represented by coarse-grained molecular models in order to present a proof-of-concept and to retain computational efficiency in the simulations. The application of the method is demonstrated in two different scenarios, namely the effective mass transport through a slit pore and the calculation of the effective self-diffusion through this system. The method allows for a distinction between diffusive and convective contributions of the mass transport.     

Effective Size of Nonrandom Mating Populations

Nonrandom mating whereby parents are related is expected to cause a reduction in effective population size because their gene frequencies are correlated and this will increase the genetic drift. The published equation for the variance effective size, Ne, which includes the possibility of nonrandom mating, does not take into account such a correlation, however. Further, previous equations to predict effective sizes in populations with partial sib mating are shown to be different, but also incorrect. In this paper, a corrected form of these equations is derived and checked by stochastic simulation. For the case of stable census number, N, and equal progeny distributions for each sex, the equation is [formula: see text], where Sk2 is the variance of family size and alpha is the departure from Hardy-Weinberg proportions. For a Poisson distribution of family size (Sk2 = 2), it reduces to Ne = N/(1 + alpha), as when inbreeding is due to selfing. When nonrandom mating occurs because there is a specified system of partial inbreeding every generation, alpha can be substituted by Wright's FIS statistic, to give the effective size as a function of the proportion of inbred mates.     

On estimating number of genes by genotype assay.

The method of genotype assay, proposed by Jinks and Towey (1976) for estimating the number of effective factors in a polygenic system, assumes independent segregation if applied to number of genes. Their results are extended to include the case of linked genes, and the ratio of expected number of effective factors to number of genes is computed for a range of models. Unless all genes are on different chromosomes or many generations of inbreeding are used, the estimate of gene number is biased downwards.     

An overview of cancer immunotherapy

The survival of patients with cancer has improved steadily but incrementally over the last century, with the advent of effective anticancer treatments such as chemotherapy and radiotherapy. However, the majority of patients with metastatic disease will not be cured by these measures and will eventually die of their disease. New and more effective methods of treating these patients are required urgently. The immune system is a potent force for rejecting transplanted organs or microbial pathogens, but effective spontaneous immunologically induced cancer remissions are very rare. In recent years, much has been discovered about the mechanisms by which the immune system recognizes and responds to cancers. The specific antigens involved have now been defined in many cases. Improved adjuvants are available. Means by which cancer cells overcome immunological attack can be exploited and overcome. Most importantly, the immunological control mechanisms responsible for initiating and maintaining an effective immune response are now much better understood. It is now possible to manipulate immunological effector cells or antigen-presenting cells ex vivo in order to induce an effective antitumour response. At the same time, it is possible to recruit other aspects of the immune system, both specific (e.g. antibody responses) and innate (natural killer cells and granulocytes).     

Metabolic futile cycles and their functions: a systems analysis of energy and control

It has long been hypothesised that futile cycles in cellular metabolism are involved in the regulation of biochemical pathways. Following the work of Newsholme and Crabtree, a quantitative theory was developed for this idea based on open-system thermodynamics and metabolic control analysis. It is shown that the stoichiometric sensitivity of an intermediary metabolite concentration with respect to changes in steady-state flux is governed by the effective equilibrium constant of the intermediate formation, and the equilibrium can be regulated by a futile cycle. The direction of the shift in the effective equilibrium constant depends on the direction of operation of the futile cycle. High stoichiometric sensitivity corresponds to ultrasensitivity of an intermediate concentration to net flow through a pathway; low stoichiometric sensitivity corresponds to super-robustness of concentration with respect to changes in flux. Both cases potentially play important roles in metabolic regulation. Futile cycles actively shift the effective equilibrium by expending energy; the magnitude of changes in effective equilibria and sensitivities is a function of the amount of energy used by a futile cycle. This proposed mechanism for control by futile cycles works remarkably similar to kinetic proofreading in biosynthesis. The sensitivity of the system is also intimately related to the rate of concentration fluctuations of intermediate metabolites. The possibility of different roles for the two major mechanisms within cellular biochemical regulation, namely reversible chemical modifications via futile cycles and shifting equilibrium by macromolecular binding, are discussed.     

Glass Transition and Delocalization in a Binary Hard-Sphere Mixture

Abstract

The glass transition of a disparate-size binary liquid and the delocalization of small particles in a glassy matrix are studied within a mode-coupling theory. The density-relaxation functions together with their long-time limits are investigated by solving space- and time-dependent mode-coupling equations numerically. We focus our attention on the effective-potential fluctuations produced by the glassy matrix, which the small particles will experience when they move through the matrix. It is found that in a strongly localized state the spatial correlations of effective-potential fluctuations are well represented by a Gaussian function. For the small particles with a long localization length, on the other hand, the effective potential is no longer Gaussian, reflecting the structure of the glassy matrix established by the big particles. The time-dependence of the effective potential is also investigated.