Generalized Rank Transformations for Tests of Survival

The asymptotic equivalence of nonparametric tests and parametric tests based on rank-transformed data (CONOVER and IMAN , 1981) can be extended to the case of censoring. This paper presents generalized rank transformations for analyses of censored data, of interval-censored data and of survival data with uncertain causes of death. A Monte Carlo study and an analysis of leukemia remission times demonstrate excellent agreement of suggested procedures with GEHAN 'S (1965) and PRENTICE 'S (1978) tests.     

A Note on Non-Parametric Tests for the Change-Point Problem

Two general classes of non-parametric tests for the change-point problem are introduced. In-variance principles lead to accessible asymptotic distribution theory.     

Rank Covariance Methods for the Analysis of Survival Data

A procedure for comparing survival times between several groups of patients through rank analysis of covariance was introduced by WOOLSON and LACHENBRUCH (1983). It is a modification of Quade' rank analysis of covariance procedure (1967) and can be used for the analysis of right-censored data. In this paper, two additional modifications of Quade' original test statistic are proposed and compared to the original modification introduced by Woolson and Lachenbruch. These statistics are compared to one another and to the score test from Cox' proportional hazards model by way of a limited Monte Carlo study. One of the statistics, Q_R2, is recommended for general use for the rank analysis of covariance of right-censored survivorship data.     

Information in Observation Under the Correlated Linear Model

In this paper we propose a measure of information in a set of observations under a given design and the linear model with the observations being correlated. We then compare the different sets of observations with respect to the information measure in the situations where the underlying designs are nested and split-plot. AMS 1970 Subject Classification: Secondary 62J05, 62J10, 62K05, 62K10, 62K15, 62K99.     

A Closed-form Jackknife Solution for the Behrens-Fisher Problem

A simple, closed-form jackknife estimate of the actual variance of the Mann-Whitney-Wilcoxon statistic, as opposed to the standard permutational variance under the test's null hypothesis has been derived which permits avoiding anticonservative performance in the presence of heterosce-dasticity. The formulation given allows modifications of the exponential scores test, of censored data tests by Gehan (1965), Peto & Peto (1977) and Prentice (1978), of tests for monotonic τ association by Kendall (1962) and for tests of ordered k-sample hypotheses. A Monte Carlo study supports recommendations for the jackknife procedures, but also shows their limited advantages in exponential scores and censored data versions. Thus, the paper extends results by Fligner & Policello (1981).     

Randomization Modelling of the Crossover Experiment for Clinical Trials

The two-period cross-over experiment for clinical trials has been examined by several writers following a Gaussian linear model approach. Some authors have expressed interest in the “derivation of the finite permutation model” and have pointed out that the randomization approach to modeling the two-period cross-over design “would highlight the importance of randomizing the subjects to the two groups as a basis for inference”. However, in the literature, there is no development of the randomization approach to this important design. In this paper, after a statement of the experimental design and formulation of the observation random variables of the finite population, two additive randomization models—one with residual effects, the other without—which are the analogues of Grizzle's Gaussian models, are derived. Statistical inference is developed for these randomization models and the results are compared with those of the corresponding Gaussian models. Also, exact inference based upon Fischer's approach is presented.     

A Comparison between the LEHMACHER & WALL Rank Tests and Pyhel's Permutation Test for the Analysis of r Independent Samples of Response Curves

LEHMACHER & WALL'S (1978) example of the application of a rank test for the comparison of two independent samples of response curves is reanalyzed by PYHEL'S (1980) permutation test for the hypothesis of parallelism of response curves. This permutation test is part of a complete evaluation of effects for a split-plot design using the permutation test based procedure by WILLMES & PYHEL (1981). Differences in test decisions are discussed.     

Efficiency in the Use of Hotellings T2

Alternative scale models are compared with regard to the Pitman efficiency of Hotelling's T² in tests for means. A basic decomposition identifies subspaces of the parameters in which one model is more efficient than another, or the two models have equal efficiency. Local and global bounds for relative Pitman efficiencies are given with reference to these subspaces. Applications include efficiency comparisons of marginal and conditional tests in a given model, and a comparison of the sensitivities of selected T² tests regarding psychological profiles in treated and control groups of children.     

A Weighted Nonparametric Procedure for the Combination of Independent Events

A weighted inverse normal procedure for combining independent events is considered. The procedure is utilized to combine results from six clinical studies on homovanillic acid concentrations in relation to the hypothesis that schizophrenia is the result of dopaminergic hyperactivity.     

Likelihood Under the Mixed Model for Quantitative Traits

Mathematical details of obtaining the likelihood functions for testing hypotheses under the mixed model for quantitative traits are given. Since families are assumed to be chosen by the value of the trait of a particular family member, conditional distributions are required. Algorithms for efficient computation of the likelihood are given.     

Design checkpoint kinase 2 inhibitors by pharmacophore modeling and virtual screening techniques

Damage to DNA is caused by ionizing radiation, genotoxic chemicals or collapsed replication forks. When DNA is damaged or cells fail to respond, a mutation that is associated with breast or ovarian cancer may occur. Mammalian cells control and stabilize the genome using a cell cycle checkpoint to prevent damage to DNA or to repair damaged DNA. Checkpoint kinase 2 (Chk2) is one of the important kinases, which strongly affects DNA-damage and plays an important role in the response to the breakage of DNA double-strands and related lesions. Therefore, this study concerns Chk2. Its purpose is to find potential inhibitors using the pharmacophore hypotheses (PhModels) and virtual screening techniques. PhModels can identify inhibitors with high biological activities and virtual screening techniques are used to screen the database of the National Cancer Institute (NCI) to retrieve compounds that exhibit all of the pharmacophoric features of potential inhibitors with high interaction energy. Ten PhModels were generated using the HypoGen best algorithm. The established PhModel, Hypo01, was evaluated by performing a cost function analysis of its correlation coefficient (r), root mean square deviation (RMSD), cost difference, and configuration cost, with the values 0.955, 1.28, 192.51, and 16.07, respectively. The result of Fischer’s cross-validation test for the Hypo01 model yielded a 95% confidence level, and the correlation coefficient of the testing set (r_test) had a best value of 0.81. The potential inhibitors were then chosen from the NCI database by Hypo01 model screening and molecular docking using the cdocker docking program. Finally, the selected compounds exhibited the identified pharmacophoric features and had a high interaction energy between the ligand and the receptor. Eighty-three potential inhibitors for Chk2 are retrieved for further study.     

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.     

On the Equivalence of the Information-Theoretic Transmission-Measure to the Common χ2 Statistic

The results of a simulation study are presented in which the χ²-and the information theoretic approach to association measurement were compared to one another. It could be shown that neither the maximal values nor the minimal values obtainable for a given sample size coincide in all cases. The underlying association concepts are defined; implications are discussed.     

运用双重组合设计建立黑龙江省玉米降水产量模型

本文运用旋转设计进一步发展的双重组合试验设计,建立黑龙江省关于降水、有机质、氮、磷、钾肥及有机肥的玉米产量模型,探讨了双重组合试验设计在建模时用可控因素去挂接不可控因素的应用,对模型进行了检验和频数分析,提出玉米产量大子3000公斤的高产在艺措施．     

New Methods for Chemo-Enzymatic Galactosidation of 2S Rapeseed Protein

Two chemo-enzymatic methodologies to synthesize neoglycoproteins from rapeseed 2S protein (napin) were developed. In the first approach, glycosidases were used to catalyse 1-O-glycosylation of serine residues, whereas in the second one, 6-N-galactosylation was examined using an amino-reduction reaction between the epsilon-NH2 of lysine residues and 6-oxogalactosides (readily available by means of the oxidation reaction of the corresponding galactosides mediated by galactose oxidase). Our results indicated that glycosidases were unable to glycosylate native proteins. Conversely, this reaction was possible, although in low yields (10%), after the introduction of a hydroxyethylene spacer. The latter modified proteins were obtained via the condensation of epsilon-NH2 of lysines with ethylene carbonate in basic medium (40% yield). The second approach was much more efficient, as 61% of the lysine residues were shown to be 6-N-galactosylated using sodium cyanoborohydride as a reduction reagent.     

Some Results for the Normal Manova Linear Functional Relationships Model

Given the normal multivariate linear regression model Y = BX + E, with B subjected to the linear restrictions H BJ = W A, J known, W and H unknown, A known, the maximum likelihood estimates of H, B, W, are obtained. A likelihood ratio test criterion for testing H = H₀, W = W₀ is provided. The results are extended to the GMANOVA model. All results are obtained in terms of the original variates directly, unlike Healy (1980) who obtains the results for the MANOVA model in terms of the canonical transformations of the original variates.     

A Visco-hyperelastic Model With Damage for the Knee Ligaments Under Dynamic Constraints

The aim of this study was to identify the behaviour laws governing the knee ligaments, accounting for the damage incurred by the structure under dynamic constraints. The model is developed using a thermodynamic formulation based on the coupling between a viscoelastic model and a damage model. Identification is carried out using the results of dynamic traction tests performed on a bone ligament/bone complex to which traction velocities of around 1.98 m/s were applied. The results show the ability of the model to account for the brittle and ductile failure processes occurring in the cruciate and lateral ligaments, respectively.     

Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor

The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity.