An Efficient Regression Type Estimator in Survey Sampling

For the estimation of population mean in simple random sampling, an efficient regression-type estimator is proposed which is more efficient than the conventional regression estimator and hence than mean per unit estimator, ratio and product estimators and many other estimators proposed by various authors. Some numerical examples are included for illustration.     

Protein folding in confined and crowded environments

Confinement and crowding are two major factors that can potentially impact protein folding in cellular environments. Theories based on considerations of excluded volumes predict disparate effects on protein folding stability for confinement and crowding: confinement can stabilize proteins by over 10k_BT but crowding has a very modest effect on stability. On the other hand, confinement and crowding are both predicted to favor conformations of the unfolded state which are compact, and consequently may increase the folding rate. These predictions are largely borne out by experimental studies of protein folding under confined and crowded conditions in the test tube. Protein folding in cellular environments is further complicated by interactions with surrounding surfaces and other factors. Concerted theoretical modeling and test-tube and in vivo experiments promise to elucidate the complexity of protein folding in cellular environments.     

The Chemical Potential of Dense Liquids by the Coupled Test Particle Method

Abstract

A new method for chemical potential estimation is proposed which is based on the coupled particle approach. The coupled particle method defines an attractive solution to the weighting function problem in umbrella sampling, bridging the gap between f and g distributions at high density. A way of eliminating the origin singularity is suggested, which is similar in spirit to the restricted umbrella sampling of Shing and Gubbins, but which is based on geometric rather than energetic criteria.

The method is illustrated on the Lennard-Jones system up to a reduced density ρ? = 1.1 along the isotherm T? = 1.2 and results are compared with the test particle insertion method and empirical equations of state. The new method is particularly useful at high liquid densities where it is superior to the other methods relying on the degree of overlap of f and g distributions. It gives reliable estimates of the chemical potential in the whole range of liquid densities.     

单分子PCR产物错误率分析

碱基错配致使PCR扩增产物中存在突变序列.大量模板PCR扩增时突变序列所占的比例较低,对随后进行的PCR产物分析影响不大,但当对微量甚至单个模板DNA扩增时,情况则完全不同.对单分子PCR产物的错误率进行了理论分析,结果表明：根据实验目的和条件,选择忠实性不同的聚合酶是十分关键的.     

Molecular Evolution of Hemojuvelin and the Repulsive Guidance Molecule Family

Repulsive guidance molecules (RGMs) are found in vertebrates and chordates and are involved in embryonic development and iron homeostasis. Members of this family are GPI-linked membrane proteins that contain an N-terminal signal peptide, a C-terminal propeptide, and a conserved RGD motif. Vertebrates are known to possess three paralogues; RGMA and RGMB (sometimes called Dragon) are expressed in the nervous system and are thought to play various roles in neural development. Hemojuvelin (HJV; also called repulsive guidance molecule c, RGMC) is the third member of this family, and mutations in this gene result in a form of juvenile hemochromatosis (type 2A). Phylogenetic analyses of 55 different RGM family sequences from 21 different species support the existence of a novel gene, found only in fish, which we have labeled RGMD. The pattern of conserved residues in each family identifies new candidates for important functional roles, including ligand binding. [Reviewing Editor: Dr. Gail Simmons]     

Ranked Set Sampling and the Line Intercept Method: A More Efficient Procedure

Ranked set sampling is a method which may be used to increase the efficiency of the estimator of the mean of a population. Ranked set sampling with size biased probability of selection (i.e., the items are selected with probability proportion to its size) is combined with the line intercept method to increase the efficency of estimating cover, density and total amount of some variable of interest (e.g. biomass). A two-stage sampling plan is suggested with line intercept sampling in the first stage. Simple random sampling and ranked set sampling are compared in the second stage to show that the unbiased estimators of density, cover and total amount of some variable of interest based on ranked set sampling have smaller variances than the usual unbiased estimator based on simple random sampling. Efficiency is increased by reducing the number of items which are measured on a transect or by increasing the number of independent transects utilized in a study area. An application procedure is given for estimation of coverage, density and number of stems of mountain mahogany (Cercocarpus montanus) in a study area east of Laramie, Wyoming.     

单分子免疫检测技术研究进展*

早诊断、早发现、早治疗是提升肿瘤患者生存率的主要手段。临床常用的免疫学检测方法如酶联免疫吸附法、化学发光法等,其检测灵敏度多限制在10^-14~10^-12 mol/L,无法满足早期诊断的需求。单分子免疫检测法,可将待检测分子限制在极小空间范围内(nL以下),对检测信号进行绝对计数,从而实现痕量(可达10^-18 mol/L)标志物的检测。这一超高灵敏度技术实现的关键在于将检测范围限制在极小体积内。经过数十年发展,不论是物理隔离还是利用纳米孔,抑或通过改进显微镜性能,均可在极小体积内(10^-21 L)对信号进行检测。目前基于微阵列的SimoA检测系统已成为单分子免疫检测的金标准,Quanterix公司基于此开发的HD-1分析仪已进入市场应用。基于微液滴的单分子免疫检测技术主要限于实验室,但具有床旁检测的优势。重点介绍了基于物理隔离形式如微阵列和微液滴的单分子免疫检测进展,为进一步开发超高灵敏度检测方法并促进未来临床应用提供理论基础。     

Optimum Design in Multivariate Stratified Sampling

The procedure of determining the optimum sample size in each stratum in stratified sampling for several variables is expressed and solved as a multistage decision process through dynamic programming. Using data published elsewhere, the dynamic programming approach was shown to give results identical to those obtained by some other already suggested approaches. The advantage is that dynamic programming can more easily handle problems involving several strata and/or variables.     

Elimination of self-association as the source of the thermodynamic nonideality in aqueous proline solutions

The effect of high concentrations of proline on the diffusion coefficient of water has been examined to assess the extent to which the resulting thermodynamic nonideality could be explained on the statistical-mechanical basis of excluded volume. In fact, such a space-filling role not only accounts for the proline concentration-dependence of the diffusion coefficient of water but it also accounts for the nonideality of proline in freezing point depression and isopiestic measurements. These findings refute the conclusion (Schobert, B. and Tschesche, H. (1978) Biochim. Biophys. Acta 541, 270–277) that the stabilization of enzyme structure by high concentrations of proline stems from self-association of the imino acid via intermolecular hydrogen bonding; and thereby support the concept that the protective effect of proline on enzyme stability must reside mainly in its action as an inert, space-filling solute.     

Molecular simulation of volume of mixing,Helmholtz free energy of mixing and entropy of mixing in bulk fluid mixtures

We describe a kinetic Monte Carlo molecular simulation procedure to calculate the Helmholtz free energy, the entropy and the chemical potentials of all components in a bulk fluid mixture. This allows us to derive the excess properties (volume, free energy and entropy) resulting from the mixing of homogeneous fluids of pure components at constant temperature and pressure. We have chosen neon–xenon mixtures to illustrate our method because of the large difference in collision diameter and well-depth of the interaction energy. When xenon is predominant in the mixture, the volume of mixing is larger. The excess entropy of mixing correlates with the volume of mixing, since a positive excess volume enables more configurations (more possible molecular distributions). The excess thermodynamic quantities as functions of the total density were found to be insensitive to temperature. To investigate the effects of the molecular parameters, we also studied argon–nitrogen and argon–krypton mixtures. The effect of the difference in molecular parameters is in the order: argon–nitrogen < argon–krypton < neon–xenon. A large difference in the well-depth of the interaction energies results in an increase in the excess thermodynamic variables, which is in agreement with the literature McDonald IR. NpT-ensemble Monte Carlo calculations for binary liquid mixtures. Mol Phys. 1972;23(1):41–58; Singer JVL, Singer K. Monte Carlo calculation of thermodynamic properties of binary mixtures of Lennard-Jones (12-6) liquids. Mol Phys. 1972;24(2):357–390.     

非损伤性取样研究进展

非损伤性取样即在不捕获、触及,甚至是未亲眼见到动物的情况下,收集不同形式的样品获取样品中的DNA。通过介绍各种类型非损伤性取样的研究进展,就该取样存在的问题及现有解决方法进行讨论,并在此基础上对非损伤性取样的研究和应用前景进行了分析,以期对进一步研究提供有价值的参考。     

Influence of Meso and Nanoscale Structure on the Properties of Highly Efficient Small Molecule Solar Cells

The nanoscale morphology of the bulk heterojunction absorber layer in an organic solar cell (OSC) is of key importance for its efficiency. The morphology of high performance vacuum‐processed, small molecule OSCs based on oligothiophene derivatives (DCV5T‐Me) blended with C₆₀ on various length scales is studied. The analytical electron microscopic techniques such as scanning transmission electron microscopy, energy dispersive X‐ray spectroscopy, highly sensitive external quantum efficiency measurements, and meso and nanoscale simulations are employed. Unique insights into the relation between processing, morphology, and efficiency of the final devices are obtained. It is shown that the connectivity of the oligothiophene‐C₆₀ network is independent of the material domain size. The decisive quantity controlling the internal quantum efficiency is the energetic disorder induced by material mixing, strongly limiting charge and exciton transport in the OSCs.     

Comparative Estimation of Genetic Diversity in Population Studies using Molecular Sampling and Traditional Sampling Methods

Entomopathogenic nematodes (EPN) are efficient biological pest control agents. Population genetics studies on EPN are seldom known. Therefore, it is of interest to evaluate the significance of molecular sampling method (MSM) for accuracy, time needed, and cost effectiveness over traditional sampling method (TSM). The study was conducted at the Mohican Hills golf course at the state of Ohio where the EPN H. bacteriophora has been monitored for 18 years. The nematode population occupies an area of approximately 3700 m² with density range from 0.25-2 per gram soil. Genetic diversity of EPN was studied by molecular sampling method (MSM) and traditional sampling method (TSM) using the mitochondrial gene pcox1. The MSM picked 88% in compared to TSM with only 30% of sequenced cox 1 gene. All studied genetic polymorphism measures (sequence and haplotype) showed high levels of genetic diversity of MSM over TSM. MSM minimizes the chance of mitochondrial genes amplification from non target organisms (insect or other contaminating microorganisms). Moreover, it allows the sampling of more individuals with a reliable and credible representative sample size. Thus, we show that MSM supersedes TSM in labour intensity, time consumption and requirement of no special experience and efficiency.     

Parameter Estimation in Systematic Sampling

First it is shown that an estimate of the variance of the sample-mean in systematic sampling from a non-autocorrelated population with linear trend, which is published in textbooks, isn't a suitable estimate: It is biased and not dependent on the essential parameter, the slope of the linear trend. In section 2 an unbiased estimate of the variance is given. As estimate of the sample-mean we take the same as usually used in literature. In section 3 a centric estimate of the sample-mean is introduced, which takes into consideration the slope of the trendline. It is shown that this estimate is unbiased; an unbiased estimate of its variance is given.     

Potentials for Molecular Dynamics Simulation of Silicate Glasses

A new potential model has been developed for the simulation of amorphous silica based on the ab initio potential model of Pyper. This model promises to be of value in the simulation of silica at high pressures.     

Biochemical Characterization of Different Molecular Forms of the Neural Cell Adhesion Molecule L1

The neural cell adhesion molecule L1 is a phosphorylated, integral membrane glycoprotein that is recovered from adult mouse brain tissue by immunoaffinity chromatography as a set of polypeptides with apparent molecular masses of 200, 180, 140, and 80 kilodaltons (L1–200, L1–180, L1–140, and L1–80, respectively). It has been shown that L1–140 and the phosphorylated L1–80 is generated from L1–200 by mild proteolytic treatment of intact cells. In the present study we have investigated the structural relationships between the different molecular forms of L1 and their location with regard to the surface membrane. We could show that L1–200 has two preferred cleavage sites, one that generates the amino terminal, extracellularly exposed L1–140 and the carboxy terminal L1–80 that spans the membrane. Cleavage at the other site leads to the generation of the amino terminally located L1–180 and the membrane-attached, phosphorylated carboxy terminal L1–30. This site is cleaved during treatment of live cultured cells with broad-spectrum, protease-free phospholipase C (but not phosphatidylinositol-specific phospholipase C) or exposure to sodium azide or cyanogen bromide. Other conditions that cause damage to cells do not lead to the generation of L1–180 and L1–30, suggesting a particular cell-intrinsic cleavage mechanism. L1–180 is truly soluble in aqueous solutions, since it can be recovered from culture supernatants and in the supernatant of a crude membrane fraction after incubation for 2 h at 37°C. Although trypsin treatment alone does not release L1–140 into the supernatant, combination of phospholipase C and mild tryptic treatment leads to the release of L1–140 and L1–50, the latter being most likely the extracellularly exposed domain of L1–80 that is complementary to the membrane-integrated phosphorylated L1–30. Phase separation experiments with Triton X-114 show that the released forms of L1–180 and L1–140 distribute into the aqueous phase, whereas they distribute into the detergent phase when in association with L1–200 or L1–80. However, when L1–80 is cleaved to yield the soluble L1–50 and membrane-anchored L1–30, L1–140 is released into the supernatant together with L1–50. A strong affinity of L1–200, L1–140, and L1–80 to each other is also indicated by the fact that they incorporate together into liposomes and separate only under strong detergent conditions. Also, a strong tendency to aggregate is observed for L1-containing liposomes, but not for those containing the adhesion molecules neural cell adhesion molecule and myelin-associated glycoprotein. Although the physiological roles of the soluble L1 forms, their mode of generation, and the strong affinity for each other remain to be investigated, the availability of soluble forms of L1 opens the possibility to use them as probes for the functional properties of L1 in assay systems involving live cells in vitro.     

Transition Path Sampling Study of the Local Molecular Structure in the Aqueous Solvation of Sodium Chloride

Abstract

The aqueous solvation of sodium chloride has been investigated using the recently introduced technique of the transition path sampling. We performed a series of Monte Carlo simulations for each element of an ensemble of chains of states. The evolution of the local solvent structure during the dissociation process has been observed. The incoming of a couple of waters to the first coordination shell is responsible for the structural changes which allow the dissociation occur: waters which leave the second coordination shell produce voids and a local molecular reorganization in order to allocate the dissociated ion pair.     

植物体内重要的信号分子--H2O2

越来越多的证据表明,植物体内的H2O2作为信号分子发挥作用.在病原、诱发因子和激素应答中是调节细胞程序性死亡的关键因子.H2O2在环境胁迫防御反应中的信号作用也得到证实.已知H2O2直接调节无数基因的表达,其中有些基因与植物防御和超敏反应有关.H2O2还与其它信号系统特别是激素信号相互作用,是激素介导的信号传导通路上的上游或下游组分;更重要的是H2O2还影响和修饰其它第二信使如钙信号的作用,在H2O2信号和钙信号之间发生众多的交互作用且这两种信号分子都调节植物对多种胁迫的交互耐性.此外,现已广泛地认识到与H2O2相关的氧还状态调节是调整细胞活动的关键因子.本文主要概括和讨论了H2O2在不同生物过程中的信号作用.     

Effects of macromolecular crowding agents on protein folding in vitro and in silico

Proteins fold and function inside cells which are environments very different from that of dilute buffer solutions most often used in traditional experiments. The crowded milieu results in excluded-volume effects, increased bulk viscosity and amplified chances for inter-molecular interactions. These environmental factors have not been accounted for in most mechanistic studies of protein folding executed during the last decades. The question thus arises as to how these effects—present when polypeptides normally fold in vivo—modulate protein biophysics. To address excluded volume effects, we use synthetic macromolecular crowding agents, which take up significant volume but do not interact with proteins, in combination with strategically selected proteins and a range of equilibrium and time-resolved biophysical (spectroscopic and computational) methods. In this review, we describe key observations on macromolecular crowding effects on protein stability, folding and structure drawn from combined in vitro and in silico studies. As expected based on Minton’s early predictions, many proteins (apoflavodoxin, VlsE, cytochrome c, and S16) became more thermodynamically stable (magnitude depends inversely on protein stability in buffer) and, unexpectedly, for apoflavodoxin and VlsE, the folded states changed both secondary structure content and, for VlsE, overall shape in the presence of macromolecular crowding. For apoflavodoxin and cytochrome c, which have complex kinetic folding mechanisms, excluded volume effects made the folding energy landscapes smoother (i.e., less misfolding and/or kinetic heterogeneity) than in buffer.