Determining equilibrium constants for dimerization reactions from molecular dynamics simulations

With today's available computer power, free energy calculations from equilibrium molecular dynamics simulations "via counting" become feasible for an increasing number of reactions. An example is the dimerization reaction of transmembrane alpha-helices. If an extended simulation of the two helices covers sufficiently many dimerization and dissociation events, their binding free energy is readily derived from the fraction of time during which the two helices are observed in dimeric form. Exactly how the correct value for the free energy is to be calculated, however, is unclear, and indeed several different and contradictory approaches have been used. In particular, results obtained via Boltzmann statistics differ from those determined via the law of mass action. Here, we develop a theory that resolves this discrepancy. We show that for simulation systems containing two molecules, the dimerization free energy is given by a formula of the form ΔG ∝ ln(P(1) /P(0) ). Our theory is also applicable to high concentrations that typically have to be used in molecular dynamics simulations to keep the simulation system small, where the textbook dilute approximations fail. It also covers simulations with an arbitrary number of monomers and dimers and provides rigorous error estimates. Comparison with test simulations of a simple Lennard Jones system with various particle numbers as well as with reference free energy values obtained from radial distribution functions show full agreement for both binding free energies and dimerization statistics.     

Multivariate statistical identification of human bladder carcinomas using ambient ionization imaging mass spectrometry

Diagnosis of human bladder cancer in untreated tissue sections is achieved by using imaging data from desorption electrospray ionization mass spectrometry (DESI-MS) combined with multivariate statistical analysis. We use the distinctive DESI-MS glycerophospholipid (GP) mass spectral profiles to visually characterize and formally classify twenty pairs (40 tissue samples) of human cancerous and adjacent normal bladder tissue samples. The individual ion images derived from the acquired profiles correlate with standard histological hematoxylin and eosin (H&E)-stained serial sections. The profiles allow us to classify the disease status of the tissue samples with high accuracy as judged by reference histological data. To achieve this, the data from the twenty pairs were divided into a training set and a validation set. Spectra from the tumor and normal regions of each of the tissue sections in the training set were used for orthogonal projection to latent structures (O-PLS) treated partial least-square discriminate analysis (PLS-DA). This predictive model was then validated by using the validation set and showed a 5% error rate for classification and a misclassification rate of 12%. It was also used to create synthetic images of the tissue sections showing pixel-by-pixel disease classification of the tissue and these data agreed well with the independent classification that uses histological data by a certified pathologist. This represents the first application of multivariate statistical methods for classification by ambient ionization although these methods have been applied previously to other MS imaging methods. The results are encouraging in terms of the development of a method that could be utilized in a clinical setting through visualization and diagnosis of intact tissue.     

A Laplace transform method for order statistics from nonidentical random variables and its application in Phase-type distribution

In this paper, we derive a method for obtaining the Laplace transform of order statistics (o.s.) arising from general independent nonidentically distributed random variables (r.v.’s). A survey of the most important properties, applications and the o.s. of a Phase-type (PH) distribution are also presented. Two illustrative examples are provided.     

一种基于混合策略的自适应多输出高斯过程响应面法

针对工程结构数值模拟常常是矢量与函数(矢量函数)混合输出的特点,提出一种基于混合策略的含索引变量的矢量高斯过程响应面法,同时提出一种设计点自适应加密方法进一步提高效率。算例显示:本文方法能够优先拾取预测误差最大的点作为加密点;真实误差全部都落在最大可能误差范围之内,最大误差1.4%~1.6%远小于预设误差限5%,验证了本文方法的有效性。     

广义Pareto模型统计推断及其应用

广义Pareto分布能很好地拟合数据分布的尾部,广泛地应用于金融市场的风险管理、风险经营问题的研究。利用概率加权矩法得到了三参数广义Pareto模型的参数估计式,给出了阈值的选取方法和风险值的计算公式;利用计算机模拟,计算得出了KS检验统计量的临界值。     

漫谈统计学的应用与发展(4)

本文分两部分:第一部分通过20多个实际案例说明统计学在各个领域的广泛应用,希望使更多的人对统计学有更全面、更深切的了解;第二部分简要介绍统计学在国内外的发展概况,并通过其发展进程的介绍,进一步阐明统计学的意义与价值。同时列举更多的论据说明近代统计学是当今最重要的科学技术之一。     

概率论与数理统计课程改革的创新机制

针对课程改革的目的,结合教学实践,就概率统计课程建设和教学改革的必要性进行综合分析并主张：通过讲述概率统计理论发展史,引导学生明确学习重点;借助多媒体教学,整合教学大纲内容,系统教学;将理论与实际相联系,激发学生学习兴趣;立足基本理论,开设统计学软件实验课程．     

指数分布在概率统计教学中的纽带作用

讨论指数分布在概率统计教学中的作用.从指数分布的定义及特征出发,分五个方面提出指数分布的知识点连接教学法,以此说明指数分布在概率统计教学中的纽带作用.     

An optimization approach to adaptive multi-dimensional capital management

Firms should keep capital to offer sufficient protection against the risks they are facing. In the insurance context methods have been developed to determine the minimum capital level required, but less so in the context of firms with multiple business lines including allocation. The individual capital reserve of each line can be represented by means of classical models, such as the conventional Cramér–Lundberg model, but the challenge lies in soundly modelling the correlations between the business lines. We propose a simple yet versatile approach that allows for dependence by introducing a common environmental factor. We present a novel Bayesian approach to calibrate the latent environmental state distribution based on observations concerning the claim processes. The calibration approach is adjusted for an environmental factor that changes over time. The convergence of the calibration procedure towards the true environmental state is deduced. We then point out how to determine the optimal initial capital of the different business lines under specific constraints on the ruin probability of subsets of business lines. Upon combining the above findings, we have developed an easy-to-implement approach to capital risk management in a multi-dimensional insurance risk model.     

基于相似度和改进雷达图的概率犹豫模糊多属性决策方法

为了解决属性权重未知的概率犹豫模糊多属性决策问题,构建基于相似度和改进雷达图的多属性决策方法。首先基于概率犹豫模糊元的信息完全度构建概率犹豫模糊集的距离测度和灰色关联系数,然后基于灰色关联理想解法定义了概率犹豫模糊集的相似度,最后根据概率犹豫模糊集的相似度和改进雷达图构建多属性决策模型,并通过案例进行了验证分析。