Confidence Intervals and Tests of Hypotheses on Variance Components in an Unbalanced Two-fold Nested Design

Confidence intervals and tests of hypotheses on variance components are required in studies that employ a random effects design. The unbalanced random two-fold nested design is considered in this paper and confidence intervals are proposed for the variance components σ2/A and σ2/B. Computer simulation is used to show that even in very unbalanced designs, these intervals generally maintain the stated confidence coefficient. The hypothesis test for σ2/A based on the lower bound of the recommended confidence interval is shown to be better than previously proposed approximate tests.     

Model building and testing for the change-over design

The two-period cross-over design is discussed within the framework of univariate and multivariate analysis of variance technique; the relations between both procedures are explained. It is shown that all hypotheses of interest can be tested if the design is regarded as a special case of a repeated measurement design. Some features of the n-period change-over design are explained by discussing the model and hypotheses of a three-period design.     

Confidence Intervals on the Total Variance in an Unbalanced Two-fold Nested Design

Confidence intervals on the total variance in an unbalanced random two-fold nested design are constructed and compared. Computer simulation indicates the proposed intervals provide confidence coefficients that are generally close to the stated level.     

Activity budget and spatial distribution of Bennett's wallabies (Macropus rufogriseus) in open versus closed exhibit designs

Although many studies investigating the impacts of zoo exhibit designs on captive animals exist, none have been performed on how they influence the behavior and welfare of captive Bennett's wallabies (Macropus rufogriseus). Here, we assess the impact of exhibit design on the activity budget and spatial distribution of Bennett's wallabies. We compared animal behavior in two open exhibits (i.e. physical interaction between animals and visitors permitted) to two closed exhibits (i.e. physical interaction between animals and visitors prohibited). Behavioral data were collected using focal sampling, and spatial distribution was recorded on exhibit maps at regular time intervals. We found a significant increase in feeding and interactive behaviors in closed exhibits in comparison to open exhibits. However, other behaviors such as resting, locomotion, and vigilance did not vary with design. Functional use of space was similar between both designs; however, the effect of habituation may be relevant to consider in future studies. Although some support for visitor effects were present, our study provided no evidence for strong impacts of exhibit design on Bennett's wallaby welfare. Our study emphasizes the need for additional research into the impacts of how zoo environments affect Bennett's wallaby behavior and welfare.     

Estimating effects of a single gene and polygenes on quantitative traits from a diallel design

A genetic model is developed with additive and dominance effects of a single gene and polygenes as well as general and specific reciprocal effects for the progeny from a diallel mating design. The methods of ANOVA, minimum norm quadratic unbiased estimation (MINQUE), restricted maximum likelihood estimation (REML), and maximum likelihood estimation (ML) are suggested for estimating variance components, and the methods of generalized least squares (GLS) and ordinary least squares (OLS) for fixed effects, while best linear unbiased prediction, linear unbiased prediction (LUP), and adjusted unbiased prediction are suggested for analyzing random effects. Monte Carlo simulations were conducted to evaluate the unbiasedness and efficiency of statistical methods involving two diallel designs with commonly used sample sizes, 6 and 8 parents, with no and missing crosses, respectively. Simulation results show that GLS and OLS are almost equally efficient for estimation of fixed effects, while MINQUE (1) and REML are better estimators of the variance components and LUP is most practical method for prediction of random effects. Data from a Drosophila melanogaster experiment (Gilbert 1985a, Theor appl Genet 69:625–629) were used as a working example to demonstrate the statistical analysis. The new methodology is also applicable to screening candidate gene(s) and to other mating designs with multiple parents, such as nested (NC Design I) and factorial (NC Design II) designs. Moreover, this methodology can serve as a guide to develop new methods for detecting indiscernible major genes and mapping quantitative trait loci based on mixture distribution theory. The computer program for the methods suggested in this article is freely available from the authors.     

Optimization of Dimethoate Degradation by Brevundimonas sp. MCM B-427 Using Factorial Design: Studies on Interactive Effects of Environmental Factors

Microbial cultures were isolated from soil exposed to dimethoate, an organophosphorus insecticide. The isolate that showed maximum degradation of dimethoate was identified as Brevundimonassp. MCM B-427. The curve relating biomass accumulation and degradation revealed that aeration appeared to enhance growth rather than degradation. For optimization of environmental factors, a 2⁴ factorial experimental design was used, wherein four factors namely pH, temperature, inoculum density and aeration condition were varied simultaneously. The interaction between the factors was analyzed using MINITAB package. Degradation of dimethoate was affected by a large number of factors interacting in a complex way. Six two-way and two three-way interactions of various environmental factors were found to be statistically significant. In all the two-way interactions, the effect of one factor was more pronounced when the other was at its optimum. The three-way interactions revealed that optimization of pH, inoculum size and aeration was more critical at 40 °C than at 30 °C.The results imply the importance of studying interactions of parameters rather than optimizing individual parameters one by one. These results demonstrate complexity of the interaction and thereby imply the need for better experimental and statistical models.     

The Two Period Binary Response Cross-Over Trial

The cross-over design for clinical trials when responses are binary is discussed. Three tests which have been proposed for the analysis of this problem are compared by an assessment of their assumptions. A simple test to establish whether it is appropriate to include observations from the second period is presented.     

Breeding-habitat use by five Amazonian frogs at forest edge

Understanding patterns of speciesl habitat use and their response to dramatic changes in habitat constitutes a basis for sound conservation practice. This study examined use of breeding habitat by two rainforest-breeding frog species near primary forest edge. Nine artificial breeding pools were established along each of three transects perpendicular to continuous primary forest near Manaus, Brazil. Five frog species bred in the pools over the six-month monitoring period. For the two most abundant species, patterns of habitat use were independent of proximity to forest edge. Also,Epipedobates femoralis used pools outside the forest, in secondary growth, at the same frequency as pools inside the forest.Osteocephalus taurinus did not breed outside primary forest. These results have clear implications for conservation biology: (i) buffer zones around isolated reserves, to counter possible negative edge effects on habitat, are unnecessary for these frog species, and (ii) secondary growth habitat, which is not natural breeding habitat forE. femoralis, could serve as a source of colonists for emigration into new areas and does not represent a barrier to dispersal for this species. These results argue against generalization of edge effects for different taxa.     

基于F3种子的胚乳性状QTL区间定位

文章提出了包括胚乳效应和母体效应的胚乳性状QTL定位的统计方法,该方法的实验设计是分子标记基因型信息来自F2母体植株和F3种子胚(或植株),胚乳性状表型值来自F3单粒种子胚乳,称之为两步等级设计。同时,用计算机全面模拟以验证该模型的可行性,模拟结果表明,只要群体足够大,该模型能较有效地进行胚乳性状QTL定位并精确地估计出胚乳QTL的各种遗传效应和母体效应。     

Confidence regions for treatment effects in subgroups in biomarker stratified designs

Subgroup analysis has important applications in the analysis of controlled clinical trials. Sometimes the result of the overall group fails to demonstrate that the new treatment is better than the control therapy, but for a subgroup of patients, the treatment benefit may exist; or sometimes, the new treatment is better for the overall group but not for a subgroup. Hence we are interested in constructing a simultaneous confidence interval for the difference of the treatment effects in a subgroup and the overall group. Subgroups are usually formed on the basis of a predictive biomarker such as age, sex, or some genetic marker. While, for example, age can be detected precisely, it is often only possible to detect the biomarker status with a certain probability. Because patients detected with a positive or negative biomarker may not be truly biomarker positive or negative, responses in the subgroups depend on the treatment therapy as well as on the sensitivity and specificity of the assay used in detecting the biomarkers. In this work, we show how (approximate) simultaneous confidence intervals and confidence ellipsoid for the treatment effects in subgroups can be found for biomarker stratified clinical trials using a normal framework with normally distributed or binary data. We show that these intervals maintain the nominal confidence level via simulations.     

片断化森林的边缘效应与自然保护区的设计管理

森林片断化引起了森林边缘物理环境与生物的变化。从森林边缘向林内,光辐射,温度、湿度、风等因素发生改变,这些反过 边缘上和边缘附近的生物产生极其重要的影响。有些研究表明,生物与非生物存在明显的边缘－核心的变化梯度,而有些则没有,除了影响边缘效应的客观因素（如边缘的取向、地势、年龄等）外,主观因素对这缘效应也有影响。边缘对生物与非生物的影响因片断化森林的面积、形状以及与其他森林片连接程度的不同而不同,     

Complex role of predators in structuring soft-sediment macrobenthic communities: Implications of changes in spatial scale for experimental studies

In estuarine and coastal soft-sediment systems, the role that predators play in structuring communities appears to be variable. Attributes of a particular predator that influence its role in structuring the community include: the rate of prey consumption; the behaviour, morphology and mobility of the predator; and, in soft- sediment communities, sediment disturbances associated with feeding. Reviews of field experiments designed to assess the role of predators in influencing the structure and function of soft-sediment communities have concluded that many of the predators are generalists and there is usually a lack of competitive exclusion. Thus predation structures communities by many complex and indirect interactions that are often difficult to predict and generalize. Variations in the apparent strength and role of predation in structuring benthic communities may depend on a variety of ecosystem characteristics and/or aspects of study design. In this paper, I consider whether we have been conducting our experiments at the appropriate scales. Five case studies from Manukau Harbour (New Zealand) illustrate how small changes in the spatial scale can affect results, due to predator perceptions and prey mobility. The results of these studies demonstrate the need to identify scales at which predator effects are likely to be important and to fit experiments within the dynamics and heterogeneity of the system being studied. To do this, we need basic information on the natural history, behaviour and spatial and temporal variability of both predators and prey communities. We also need to be specific about scales of measurement when matching theoretical predictions to field observations/experiments. Finally, to enhance our ability to generalize from specific studies, we need to gather data that will enable us to both predict and test the importance of predation over a range of spatial and temporal scales.     

On Choice of Subjects and Replicates in Estimating Among and Within Subject Variation

We consider the problem of choosing the number of replicates and number of subjects in a components of variance problem which optimizes various criteria. The case study here involves patients suffering from systemic sclerosis (Scleroderma), a form of rheumatic disease that is potentially disabling. Under the physical constraints imposed on the study, we find that using 2 or 3 replicates with as many patients as possible is the optimal strategy for several criteria.     

Synthesis and evaluation of 2,9-disubstituted 8-phenylthio/phenylsulfinyl-9H-purine as new EGFR inhibitors

In present study, we described the synthesis and biological evaluation of a new class of EGFR inhibitors containing 2,9-disubstituted 8-phenylthio/phenylsulfinyl-9H-purine scaffold. Thirty-one compounds were synthesized. Among them, compound C9 displayed the IC₅₀ of 29.4?nM against HCC827 cell line and 1.9?nM against EGFR^L858R. Compound C12 showed moderate inhibitory activity against EGFR^{L858R/T790M/C797S} (IC₅₀?=?114?nM). Western bolt assay suggested that compound C9 significantly inhibited EGFR phosphorylation. In vivo test, compound C9 remarkably exhibited inhibitory effect on tumor growth at 5.0?mg/kg by oral administration in established nude mouse HCC827 xenograft model. These results indicate that the 2,9-disubstituted 8-phenylsulfinyl/phenylsulfinyl-9H-purine derivatives can act as potent EGFR(L858R) inhibitors and effective anticancer agents. Additionally, optimization of compound C12 may result in discovering the fourth-generation EGFR-TKIs.