An Efficient Timer and Sizer of Biomacromolecular Motions

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Generalized estimating equations for ordinal categorical data: arbitrary patterns of missing responses and missingness in a key covariate

We propose methods for regression analysis of repeatedly measured ordinal categorical data when there is nonmonotone missingness in these responses and when a key covariate is missing depending on observables. The methods use ordinal regression models in conjunction with generalized estimating equations (GEEs). We extend the GEE methodology to accommodate arbitrary patterns of missingness in the responses when this missingness is independent of the unobserved responses. We further extend the methodology to provide correction for possible bias when missingness in knowledge of a key covariate may depend on observables. The approach is illustrated with the analysis of data from a study in diagnostic oncology in which multiple correlated receiver operating characteristic curves are estimated and corrected for possible verification bias when the true disease status is missing depending on observables.     

Comparison of backbone dynamics of monomeric and domain-swapped stefin A

Three-dimensional domain swapping has been observed in increasing number of proteins and has been implicated in the initial stages of protein aggregation, including that of the cystatins. Stefin A folds as a monomer under native conditions, while under some denaturing conditions domain-swapped dimer is formed. We have determined the backbone dynamics of the monomeric and domain-swapped dimeric forms of stefin A by (15)N relaxation using a model-free approach. The overall correlation times of the molecules were determined to be 4.6 +/- 0.1 ns and 9.2 +/- 0.2 ns for the monomer and the dimer, respectively. In the monomer, decreased order parameters indicate an increased mobility for the N-terminal trunk, the first and the second binding loops. At the opposite side of the molecule, the loop connecting the alpha-helix with strand B, the beginning of strand B and the loop connecting strands C and D show increased localized mobility. In the domain-swapped dimer, a distinctive feature of the structure is the concatenation of strands B and C into a single long beta-strand. The newly formed linker region between strands B and C, which substitutes for the first binding loop in the monomer, has order parameters typical for the remainder of the beta-strands. Thus, the interaction between subunits that occurs on domain-swapping has consequences for the dynamics of the protein at long-range from the site of conformational change, where an increased rigidity in the newly formed linker region is accompanied by an increased mobility of loops remote from that site.     

1H,13C-1H,1H Dipolar Cross-correlated Spin Relaxation in Methyl Groups

Relaxation in methyl groups is strongly influenced by cross-correlated interactions involving the methyl dipoles. One of the major interference effects results from intra-methyl (1)H-(13)C, (1)H-(1)H dipolar interactions, leading to significant differences in the relaxation of certain multiplet components that contribute to double- and zero-quantum (1)H-(13)C spectra. NMR experiments are presented for the measurement of this differential relaxation effect. It is shown that this difference in relaxation between double- and zero-quantum multiplet components can be used as a sensitive reporter of side chain dynamics and that accurate methyl axis order parameters can be measured in proteins that tumble with correlation times greater than approximately 5 ns.     

Estimating the Location and Time Course of Synaptic Input from Multi-Site Potential Recordings

A method is introduced that permits accurate and robust extraction of the location and time course of synaptic conductance from potentials recorded on either side of, and perhaps at some distance from, the synapse in question. It is shown that such data permits one to fully overcome the problems typically associated with lack of spaceclamp. The method does not presume anything about the nature of the time course and yet is applicable to branched, active cells receiving simultaneous input from a number of synapses.     

Peptide separation by Hydrophilic-Interaction Chromatography: a review

Recent developments in the separation of peptides by high-performance liquid chromatography (HPLC) using polar sorbents with less polar eluents are summarized in this review. This separation mode is now commonly referred to as Hydrophilic-Interaction Chromatography (HILIC). The retention mechanism and chromatographic behavior of polar solutes under HILIC conditions are studied on TSKgel Amide-80 columns, which consist of carbamoyl groups bonded to a silica gel matrix, using a mixture of acetonitrile (MeCN)–water containing 0.1% trifluoroacetic acid (TFA). Some applications are given in peptide field using Hydrophilic-Interaction Chromatography.     

水葫芦苗(Halerpestes cymbalaris)的生长特征研究

以调查统计的方法在中国科学院海北定位站研究了高寒湿地植物水葫芦苗无性系的生长特征、形态特征以及能量分配规律。结果表明：匍匐茎只有1条的水葫芦苗最多,占35．29％,匍匐茎有4条的水葫芦苗只占8．82％。同一水葫芦苗无性系中,随着匍匐茎数目的增多,分株数、间隔子数、茎总长和匍匐茎比节问重变小。分株一般在第一级最高,末级较低;第1条匍匐茎的间隔子较长。随水葫芦苗匍匐茎数目的增多,用于无性繁殖的分株干重比例逐渐增加,用于有性繁殖的花的干重比例下降。水葫芦苗无性系这种生长特征、形态特征以及能量分配规律是其生物—生态学特性和所处高寒湿地生境共同决定的。     

A local influence approach applied to binary data from a psychiatric study

Recently, a lot of concern has been raised about assumptions needed in order to fit statistical models to incomplete multivariate and longitudinal data. In response, research efforts are being devoted to the development of tools that assess the sensitivity of such models to often strong but always, at least in part, unverifiable assumptions. Many efforts have been devoted to longitudinal data, primarily in the selection model context, although some researchers have expressed interest in the pattern-mixture setting as well. A promising tool, proposed by Verbeke et al. (2001, Biometrics 57, 43-50), is based on local influence (Cook, 1986, Journal of the Royal Statistical Society, Series B 48, 133-169). These authors considered the Diggle and Kenward (1994, Applied Statistics 43, 49-93) model, which is based on a selection model, integrating a linear mixed model for continuous outcomes with logistic regression for dropout. In this article, we show that a similar idea can be developed for multivariate and longitudinal binary data, subject to nonmonotone missingness. We focus on the model proposed by Baker, Rosenberger, and DerSimonian (1992, Statistics in Medicine 11, 643-657). The original model is first extended to allow for (possibly continuous) covariates, whereafter a local influence strategy is developed to support the model-building process. The model is able to deal with nonmonotone missingness but has some limitations as well, stemming from the conditional nature of the model parameters. Some analytical insight is provided into the behavior of the local influence graphs.     

冈崎姬小蜂生物学特性的研究

 对美洲斑潜蝇幼虫寄生蜂──冈崎姬小蜂Neochrysocharis okazakii Kamijo生物学特 性的研究结果表明：（1）补充蜜汁能显著延长成蜂寿命;（2）在20～33℃范围内各虫 态发育速率与温度呈线性相关,发育起点温度81℃,完成一个世代需要1887日·度的积 温;成蜂寿命与温度呈负线性相关,产卵量在30℃时达到最大;内禀增长率与温度呈线性相 关。     

Multi-compartmental modelling and experimental design for glucose transport studies in insulin-resistant rats

Many pathologies are associated with abnormalities of glucose metabolism or with perturbations of its transport (type 2 diabetes or insulin-resistance). The pre-diabetic state is characterised by a state of insulin-resistance, in others words a defect of glucose transport in insulin-sensible tissues, such as muscles and adipose tissues. The mathematical modelling of experimental data can be an excellent method to explore the mechanisms implied in the studied biological phenomenon. Thus, starting from a symbolic formulation like the compartmental modelling, it can be possible to develop a theoretical basis for the observation and to consider the best-adapted experiments for the study. We showed with mathematical models that [123I]-6-deoxy-6-iodo-D-glucose (6-DIG), shown as a tracer of glucose transport in vitro, could point out this transport abnormality. To quantify the insulin resistance, we estimated the fractional transfer coefficients of 6-DIG from the blood to the organs. We realised many studies to lead to a satisfying model; special attention has been paid to the precision of the parameter to select the best model. The results showed that by associating experimental data obtained with 6-DIG activities and an adapted mathematical model, discriminating parameters (in and out fractional transfer coefficients) between the two groups (control and insulin-resistant rats) could be pointed out.