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.     

Regression analysis of doubly censored failure time data using the additive hazards model

Doubly censored failure time data arise when the survival time of interest is the elapsed time between two related events and observations on occurrences of both events could be censored. Regression analysis of doubly censored data has recently attracted considerable attention and for this a few methods have been proposed (Kim et al., 1993, Biometrics 49, 13-22; Sun et al., 1999, Biometrics 55, 909-914; Pan, 2001, Biometrics 57, 1245-1250). However, all of the methods are based on the proportional hazards model and it is well known that the proportional hazards model may not fit failure time data well sometimes. This article investigates regression analysis of such data using the additive hazards model and an estimating equation approach is proposed for inference about regression parameters of interest. The proposed method can be easily implemented and the properties of the proposed estimates of regression parameters are established. The method is applied to a set of doubly censored data from an AIDS cohort study.     

An exactly solvable model of population dynamics with density-dependent migrations and the Allee effect

We consider a single-species model of population dynamics allowing for migrations and the Allee effect. Two types of migration are taken into account: one caused by environmental factors (e.g., a passive transport with the wind or water current) and the other associated with biological mechanisms. While the first type is apparently density-independent, the speed of migration in the second one can depend on the population density. Mathematically, this model consists of a non-linear partial differential equation of advection-diffusion-reaction type. Using an appropriate change of variables, we obtain an exact solution of the equation describing propagation of travelling population fronts. We show that, depending on parameter values and thus on the relative intensity of density-dependent and density-independent factors, the direction of the propagation can be different thus describing either species invasion or species retreat.     

The environmental zero‐point problem in evolutionary reaction norm modeling

There is a potential problem in present quantitative genetics evolutionary modeling based on reaction norms. Such models are state‐space models, where the multivariate breeder's equation in some form is used as the state equation that propagates the population state forward in time. These models use the implicit assumption of a constant reference environment, in many cases set to zero. This zero‐point is often the environment a population is adapted to, that is, where the expected geometric mean fitness is maximized. Such environmental reference values follow from the state of the population system, and they are thus population properties. The environment the population is adapted to, is, in other words, an internal population property, independent of the external environment. It is only when the external environment coincides with the internal reference environment, or vice versa, that the population is adapted to the current environment. This is formally a result of state‐space modeling theory, which is an important theoretical basis for evolutionary modeling. The potential zero‐point problem is present in all types of reaction norm models, parametrized as well as function‐valued, and the problem does not disappear when the reference environment is set to zero. As the environmental reference values are population characteristics, they ought to be modeled as such. Whether such characteristics are evolvable is an open question, but considering the complexity of evolutionary processes, such evolvability cannot be excluded without good arguments. As a straightforward solution, I propose to model the reference values as evolvable mean traits in their own right, in addition to other reaction norm traits. However, solutions based on an evolvable G matrix are also possible.     

A generalized estimating equations approach to quantitative trait locus detection of non-normal traits

To date, most statistical developments in QTL detection methodology have been directed at continuous traits with an underlying normal distribution. This paper presents a method for QTL analysis of non-normal traits using a generalized linear mixed model approach. Development of this method has been motivated by a backcross experiment involving two inbred lines of mice that was conducted in order to locate a QTL for litter size. A Poisson regression form is used to model litter size, with allowances made for under- as well as over-dispersion, as suggested by the experimental data. In addition to fixed parity effects, random animal effects have also been included in the model. However, the method is not fully parametric as the model is specified only in terms of means, variances and covariances, and not as a full probability model. Consequently, a generalized estimating equations (GEE) approach is used to fit the model. For statistical inferences, permutation tests and bootstrap procedures are used. This method is illustrated with simulated as well as experimental mouse data. Overall, the method is found to be quite reliable, and with modification, can be used for QTL detection for a range of other non-normally distributed traits.     

The stereodynamics of 1,2‐dipropyldiaziridines

N‐alkylated trans‐diaziridines are an intriguing class of compounds with two stereogenic nitrogen atoms which easily interconvert. In the course of our investigations of the nature of the interconversion process via nitrogen inversion or electrocyclic ring opening ring closure, we synthesized and characterized the three constitutionally isomeric diaziridines 1,2‐di‐n‐propyldiaziridine 1 , 1‐isopropyl‐2‐n‐propyldiaziridine 2 , and 1,2‐diisopropyldiaziridine 3 to study the influence of the substituents on the interconversion barriers. Enantiomer separation was achieved by enantioselective gas chromatography on the chiral stationary phase Chirasil‐β‐Dex with high separation factors α (1‐isopropyl‐2‐n‐propyldiaziridine: 1.18; 1, 2‐diisopropyldiaziridine: 1.24; 100°C 50 kPa He) for the isopropyl substituted diaziridines. These compounds showed pronounced plateau formation between 100 and 150°C, and peak coalescence at elevated temperatures. The enantiomerization barriers ΔG? and activation parameters ΔH? and ΔS? were determined by enantioselective dynamic gas chromatography (DGC) and direct evaluation of the elution profiles using the unified equation implemented in the software DCXplorer. Interestingly, 1‐isopropyl‐2‐n‐propyldiaziridine and 1,2‐diisopropyldiaziridine exhibit similar high interconversion barriers ΔG? (100°C) of 128.3 ± 0.4 kJ mol^?1 and 129.8 ± 0.4 kJ mol^?1, respectively, which indicates that two sterically demanding substituents do not substantially increase the barrier as expected for a distinct nitrogen inversion process. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

吉林省天然阔叶混交林生态系统多功能性及驱动因素

量化天然林生态系统的多功能性,分析不同功能间的权衡-协同关系及驱动因子,对于天然林保护及修复具有重要的意义。基于吉林省第8次森林资源清查天然阔叶混交林固定样地调查数据、土壤及气候数据,选取土壤保持、涵养水源、碳储量、气候调节、土壤肥力维持、生物多样性、生产力和木材生产8个生态系统功能来表征生态系统多功能性。利用平均值法中的最大值转换法计算多功能性指数。结果表明：（1）8个功能间权衡、协同和中性关系均存在,但以协同关系为主。生物多样性除与气候调节为权衡关系外,与其他功能均为协同关系;碳储量-木材生产协同关系最强（r=0.960,P<0.01）,气候调节-涵养水源间权衡关系最强（r=-0.934,P<0.01）;（2）吉林省天然阔叶混交林的多功能性指数在0.31-0.89之间,且生物多样性和气候调节为主导功能;（3）多功能性与驱动因子的结构方程模型确定系数为R²=0.795,多功能性的驱动因子的总路径系数依次为：林分密度指数（0.752） > 平均年龄（0.375） > 年降雨量（0.365） > 树种丰富度（0.101） > 土壤pH（0.064） > 结构多样性（-0.037） > 年均温（-0.105）,林分密度是最重要的驱动因子。结果对理解天然阔叶混交林的多功能形成及经营调控有一定的意义。     

Modelling cell death in human tumour cell lines exposed to the anticancer drug paclitaxel

Most anti-cancer drugs in use today exert their effects by inducing a programmed cell death mechanism. This process, termed apoptosis, is accompanied by degradation of the DNA and produces cells with a range of DNA contents. We have previously developed a phase transition mathematical model to describe the mammalian cell division cycle in terms of cell cycle phases and the transition rates between these phases. We now extend this model here to incorporate a transition to a programmed cell death phase whereby cellular DNA is progressively degraded with time. We have utilised the technique of flow cytometry to analyse the behaviour of a melanoma cell line (NZM13) that was exposed to paclitaxel, a drug used frequently in the treatment of cancer. The flow cytometry profiles included a complex mixture of living cells whose DNA content was increasing with time and dying cells whose DNA content was decreasing with time. Application of the mathematical model enabled estimation of the rate constant for entry of mitotic cells into apoptosis (0.035 per hour) and the duration of the period of DNA degradation (51 hours). These results provide a dynamic model of the action of an anticancer drug that can be extended to improve the clinical outcome in individual cancer patients.Revised version: 9 October 2003     

Methods and method evaluation for mycotoxins

Mycotoxins are metabolites of molds frequently found on and in agricultural commodities, food and feeds. Owing to their demonstrated acute, sub-acute and, in some cases, chronic toxicity, an effort has been made, worldwide, to control human and animal exposure to these toxic chemicals. This effort depends upon the availability of validated analytical methods for their detection and quantitation. This paper outlines the methodology available, and the procedures used to validate, i.e. evaluate, these methods based on the use of interlaboratory collaborative studies and the application of the HORRAT.