Bayesian Construction of an Improved Parametric Test for Probability‐Based Individual Bioequivalence

Assuming a lognormally distributed measure of bioavailability, individual bioequivalence is defined as originally proposed by Anderson and Hauck (1990) and Wellek (1990; 1993). For the posterior probability of the associated statistical hypothesis with respect to a noninformative reference prior, a numerically efficient algorithm is constructed which serves as the building block of a procedure for computing exact rejection probabilities of the Bayesian test under arbitrary parameter constellations. By means of this tool, the Bayesian test can be shown to maintain the significance level without being over‐conservative and to yield gains in power of up to 30% as compared to the distribution‐free procedure which gained some popularity under the name TIER. Moreover, it is shown that the Bayesian construction also allows scaling of the probability‐based criterion with respect to the proportion of subjects exhibiting bioequivalent responses to repeated administrations of the reference formulation of the drug under study.     

The role of water in the thermodynamics of dilute aqueous solutions

Water plays a role in the thermodynamics of dilute aqueous solutions that is unusual in two ways. First, knowledge of hydration equilibrium constants of species is not required in calculations of thermodynamic properties of biochemical reactants and reactions at specified pH. Second, since solvent provides an essentially infinite source of oxygen atoms in a reaction system where water is a reactant, oxygen atoms are not conserved in the reaction system in dilute aqueous solutions. This is related to the fact that H₂O is omitted in equilibrium expressions for dilute aqueous solutions. Calculations of the standard transformed Gibbs energies of formation of total carbon dioxide and total ammonia at specified pH are discussed, and the average bindings of hydrogen ions by these reactants are calculated by differentiation. Since both of these reactants are involved in the urease reaction, the apparent equilibrium constants and changes in the numbers of hydrogen ions bound are calculated for this reaction as functions of pH.     

磁共振肿瘤矩特征信息研究

目的:采用MR脑肿瘤图像分割与矩方法进行结合,以获取特定器官及组织的轮廓。方法:对MR脑肿瘤图像进行分割,并对分割的结果进行矩描述。通过分析当前常用的医学图像分割方法,采用了一种基于形变模型的医学图像分割方法,并按照相应的理论算法模型和实现步骤对医学图像进行了处理,最后用Visual C 6.0编程,并对MR脑肿瘤图像进行分割实验。结果:从切割的图形中可以看出,本分割方法分割边界清晰,总体不确定性较小,利用矩技术所提取的图像特征在基于内容的图像检索中是有效的。结论:本分割方法切实可行,分割效果较好,为进一步的MR脑肿瘤图像分析和研究提供了一种有效工具。     

远交群体动态性状基因定位的似然分析Ⅱ.模拟研究

以远交设计群体为例,在推导出动态性状基因定位的似然法分析过程的基础上,选择3阶Legendre多项式为子模型,采用Monte-Carlo方法模拟研究了不同个体数、测定日频数、标记密度和QTL遗传贡献率对两种分析方法检测QTL效率的影响。每个因素都取高、中和低3个水平,利用正交设计安排模拟因素试验组合。模拟试验结果表明：高QTL遗传贡献率要比低QTL遗传贡献率的QTL在检测时需要较少个体数和测定日抽样;但不论QTL遗传贡献率多大,300以上的群体大小和5％以上的测定日频数都可以保证足够高的检测效率。个体数和测定日频数对动态性状QTL的分析和检测具有几乎相同的作用,而且相同样本含量条件下两者呈现互补的关系。就某个动态点的QTL检测而言,模拟试验也同时证明：提出的这种以整个动态过程为定位目标的动态性状基因定位方法明显优于传统的逐个动态点的定位分析方法。     

Statistical determination of diagnostic species for site groups of unequal size

Aim: Concentration of species occurrences in groups of classified sites can be quantified with statistical measures of fidelity, which can be used for the determination of diagnostic species. However, for most available measures fidelity depends on the number of sites within individual groups. As the classified data sets typically contain site groups of unequal size, such measures do not enable a comparison of numerical fidelity values of species between different site groups. We therefore propose a new method of measuring fidelity with presence/absence data after equalization of the size of the site groups. We compare the properties of this new method with other measures of statistical fidelity, in particular with the Dufrêne‐Legendre Indicator Value (IndVal) index. Methods: The size of site groups in the data set is equalized, while relative frequencies of species occurrence within and outside of these groups are kept constant. Then fidelity is calculated using the phi coefficient of association. Results: Fidelity values after equalization are independent of site group size, but their numerical values vary independently of the statistical significance of fidelity. By changing the size of the target site group relative to the size of the entire data set, the fidelity measure can be made more sensitive to either common or rare species. We show that there are two modifications of the IndVal index for presence/absence data, one of which is also independent of the size of site groups. Conclusion: The phi coefficient applied to site groups of equalized size has advantages over other statistical measures of fidelity based on presence/absence data. Its properties are close to an intuitive understanding of fidelity and diagnostic species in vegetation science. Statistical significance can be checked by calculation of another fidelity measure that is a function of statistical significance, or by direct calculation of the probability of observed species concentrations by Fisher's exact test. An advantage of the new method over IndVal is its ability to distinguish between positive and negative fidelity. One can also weight the relative importance of common and rare species by changing the equalized size of the site groups.     

Detection of quantitative trait loci influencing growth trajectories of adventitious roots in Populus using functional mapping

The capacity to root from cuttings is a key factor for the mass deployment of superior genotypes in clonal forestry. We studied the genetic basis of rooting capacity by mapping quantitative trait loci (QTLs) that control growth rate and form of root traits in a full-sib family of 93 hybrids derived from an interspecific cross between two Populus species, P. deltoides and P. euramericana. The hybrid family was typed for different marker systems (including SSRs, AFLPs, RAPDs, ISSRs, and SNPs), leading to the construction of two linkage maps based on the female P. deltoides (D map) and male P. euramericana (E map) with a pseudotestcross mapping strategy. The two maps were scanned by functional mapping to detect QTLs that control early growth trajectories of two rooting traits, maximal single-root length and the total number of roots per cutting, measured at five time points in water culture. Of the six QTLs detected for these two growth traits, only one is segregating in P. deltoides with poor rooting capacity, while the other five are segregating in P. euramericana showing good rooting capacity. Tests with functional mapping suggest different developmental patterns of the genetic effects of these root QTLs in time course. Five QTLs were detected to change their effects on root growth trajectories with time, whereas one detected to affect root growth consistently in time course. Knowledge about the genetic and developmental control mechanisms of root QTLs will have important implications for the genetic improvement of vegetative propagation traits in Populus.     

Bayesian analysis for genetic architecture of dynamic traits

The dissection of the genetic architecture of quantitative traits, including the number and locations of quantitative trait loci (QTL) and their main and epistatic effects, has been an important topic in current QTL mapping. We extend the Bayesian model selection framework for mapping multiple epistatic QTL affecting continuous traits to dynamic traits in experimental crosses. The extension inherits the efficiency of Bayesian model selection and the flexibility of the Legendre polynomial model fitting to the change in genetic and environmental effects with time. We illustrate the proposed method by simultaneously detecting the main and epistatic QTLs for the growth of leaf age in a doubled-haploid population of rice. The behavior and performance of the method are also shown by computer simulation experiments. The results show that our method can more quickly identify interacting QTLs for dynamic traits in the models with many numbers of genetic effects, enhancing our understanding of genetic architecture for dynamic traits. Our proposed method can be treated as a general form of mapping QTL for continuous quantitative traits, being easier to extend to multiple traits and to a single trait with repeat records.     

远交群体动态性状基因定位的似然分析Ⅰ.理论方法

受动物遗传育种中用来估计动态性状育种值的随机回归测定日模型思想的启发 ,将关于时间 (测定日期 )的Legendre多项式镶嵌在遗传模型的每个遗传效应中 ,以刻画QTL对动态性状变化过程的作用 ,从而建立起动态性状基因定位的数学模型。利用远交设计群体 ,阐述了动态性状基因定位的似然分析原理 ,推导了定位参数似然估计的EM法两步求解过程。结合动态性状遗传分析的特点和普通数量性状基因定位研究进展 ,还提出了有关动态性状基因定位进一步研究的设想