一种在格点模型上模拟蛋白质折叠结构的优化算法

蛋白质折叠问题是生物信息学中一个经典的多项式复杂程度的非确定性(non-deterministic polynomial,NP)难度问题.势能曲面变平法(ELP)是一种启发式的全局优化算法.通过对ELP方法中的直方图函数提出一种新的更新机制,并将基于贪心策略的初始构象的产生,基于牵引移动的邻域搜索策略与ELP方法相结合,为面心立方体(FCC)格点模型的蛋白质折叠问题提出一种改进的势能曲面变平(ELP+)算法.采用文献中9条常用序列作为测试集.对于每条序列,ELP+算法均能找到与文献中的算法所得到的最低能量相等或更低的能量.实验结果表明,ELP+算法是求解FCC格点模型的蛋白质折叠问题的一种有效算法.     

单形格子和单形重心设计统计模型的优化分析方法

单形格子和单形重心设计是两种非常实用的配方试验设计方法,但其统计模型的优化分析却很困难．本文通过对单形格子和单形重心设计基本原理的分析,根据数学规划理论,构建了专门对这两种试验设计的统计模型进行优化分析的方法,同时给出了应用实例．     

Self Assembly of Bilayers in a Lattice Model of Amphiphile and Solvent Systems

The results of a Metropolis Monte Carlo simulation of a three dimensional lattice model of an amphiphile and solvent mixture are presented. In the model each amphiphile molecule is represented as a connected chain of lattice sites with one site representing the head and the remaining chain sites representing the tail of the molecule. The remaining sites on the lattice represent solvent molecules. The amphiphiles interact through a nearest neighbour potential which includes head-solvent and tail-solvent interactions. No prior assumption is made about the structures which may be observed.

The cluster size distribution and cluster structure is studied as a function of temperature and head-solvent interaction. If the tail-solvent interaction is solvophobic and the head-solvent interaction is solvophilic, a micellar region is observed in the phase diagram. For sufficiently solvophilic head-solvent interactions the low temperature phase exhibits self assembly into castellated bilayer structures.     

Packing analysis and the crystal chemistry of 2,5-dibenzylidenecyclopent-3-ene-1-one. Rationale for a non-topochemical solid-state reaction

The molecular and crystal structure of 2,5-dibenzylidenecyclopent-3-ene-1-one has been studied in detail to explain the formation of a non-topochemical pseudo-mirror-symmetric dimer upon photoirradiation. Packing energy calculations, analysis of the thermal motion, and lattice energy calculations are employed to analyse and understand the observed dimerization reaction, crystal structure, and crystal properties. Supplementary data relating to this article have been deposited with the British Library as Supplementary Publication No. SUP 82137 (6 pages).     

Motion parallax as a source of distance information in locusts and mantids

This review article is devoted to results on distance measurement in locusts (e.g., Wallace, 1959; Collett, 1978; Sobel, 1990) and mantids. Before locusts or mantids jump toward a stationary object, they perform characteristic pendulum movements with the head or body, called peering movements, in the direction of the object. The fact that the animals over- or underestimate the distance to the object when the object is moved with or against the peering movement, and so perform jumps that are too long or short, would seem to indicate that motion parallax is used in this distance measurement. The behavior of the peering parameters with different object distances also indicates that not only retinal image motion but also the animal’s own movement is used in calculating the distance.     

Estimation and Verification of Hypotheses in Some Zyskind-Martin Models with Missing Values

Several theorems on estimation and verification of linear hypotheses in some Zyskind-Martin (ZM) models are given. The assumptions are as follows. Let y = Xβ + e or (y, Xβ, σ²V) be a fixed model where y is a vector of n observations, X is a known matrix nXp with rank r(X) = r ≦ p < n, where p is a number of coordinates of the unknown parameter vector β, e is a random vector of errors with covariance matrix σ²V, where σ² is unknown scalar parameter, V is a known non-negative definite matrix such that R(X) ? R(V). Symbol R(A) denotes a vector space generated by columns of matrix A. The expected value of y is Xβ. In this paper four following Zyskind-Martin (ZM) models are considered: ZMd, ZMa, ZMc and ZMqd (definitions in sec. 1) when vector y y₁ y₂ involves a vector y₁ of m missing values and a vector y₂ with (n — m) observed values. A special transformation of ZM model gives again ZM model (cf. theorem 2.1). Ten properties of actual (ZMa) and complete (ZMc) Zyskind-Martin models with missing values (cf. theorem 2.2) test functions F are given in (2.11)) are presented. The third propriety constitutes a generalization of R. A. Fisher's rule from standard model (y, Xβ, σ²I) to ZM model. Estimation of vector y₁ (cf. 3.3) of vector β (cf. th. 3.2) and of scalar σ² (cf. th. 3.4) in actual ZMa model and in diagonal quasi-ZM model (ZMqd) are presented. Relation between y? ₁ and β is given in theorem 3.1. The results of section 2 are illustrated by numerical example in section 4.     

我国疾病动物模型的研究现状和展望

由于医学科学研究的需要,各类疾病动物模型被广泛用来研究人类疾病的发生发展机制、药物筛选以及治疗评价等.本文全面梳理了我国疾病动物模型的研究和发展现状,分析了我国在这方面的特色优势以及与国际上的差距,内容涵盖了肿瘤、神经及精神疾病、感染及免疫性疾病、心血管与代谢性疾病、药物筛选等不同领域.简要介绍了国家自然科学基金对疾病动物模型项目的资助情况,同时指出了我国疾病模型今后的主要发展方向.     

Models and detection of spontaneous recurrent seizures in laboratory rodents

Epilepsy,characterized by spontaneous recurrent seizures (SRS),is a serious and common neurological disorder afflicting an estimated 1％ of the population worldwide.Animal experiments,especially those utilizing small laboratory rodents,remain essential to understanding the fundamental mechanisms underlying epilepsy and to prevent,diagnose,and treat this disease.While much attention has been focused on epileptogenesis in animal models of epilepsy,there is little discussion on SRS,the hallmark of epilepsy.This is in part due to the technical difficulties of rigorous SRS detection.In this review,we comprehensively summarize both genetic and acquired models of SRS and discuss the methodology used to monitor and detect SRS in mice and rats.     

Spatial pattern analysis in forest dynamics: deviation from power law and direction of regeneration waves

Grid-based models have been used to understand spatial heterogeneity of the vegetation height in forests and to analyze spatio-temporal dynamics of the forest regeneration process. In this report, we present two methods of identifying lattice models when spatio-temporal data are given. The first method detects directionality of regeneration waves based on the timing of local disturbance events. The second evaluates the forest pattern by recording the fraction of high and low vegetation areas at multiple spatial scales. We illustrate these methods by applying them to patterns generated using three simple stochastic lattice models: (1) two-state model, distinguishing sites with high and low vegetation, (2) three-state model, in which sites can be in an additional disturbed state, and (3) Shimagare model, which considers a continuous range of states. The combination of the two methods provides efficient means of distinguishing the models. The first method has a more direct ecological meaning, while the second is useful when forest data are limited in time.     

CRISPR-Cas9系统在疾病模型中的应用

规律成簇间隔短回文重复（CRISPR）及相关核酸内切酶（Cas）系统是最近发现的一种关于RNA指导核酸内切酶的基因编辑技术,这一技术的发现促进了生物学和医学研究的发展。CRISPR-Cas9系统的简便性使其广泛应用于细胞基因组编辑、动物模型的构建及疾病模型的基因治疗。现就CRISPR-Cas9系统的结构特点、作用机制及应用进行了综述。     

Potentials and limitations of quantification of fungi in freshwater environments based on PLFA profiles

Aquatic fungi are increasingly recognized for their contribution to carbon cycling in aquatic ecosystems, both as saprotrophs and parasites. Their quantification in mixed communities is crucial to assess their ecological significance but remains challenging. We characterized the phospholipid-derived fatty acid (PLFA) composition of fifteen aquatic fungal isolates from Chytridiomycota (chytrids) and Dikarya. Additionally, we identified PLFA patterns of chytrids infecting phytoplankton and their zoospores. PLFA composition of zoospores was highly similar among different taxa, but were distinct from their respective sporangial life-stage. Finally, we applied a fatty acid-based Bayesian mixed model (FASTAR) and tested its potential to quantify fungi in complex mixtures with bacteria and phytoplankton using PLFA profiles. While the quantification of chytrid biomass in low quantities was rather imprecise, the model predicted the contribution of filamentous fungi and other components with fair accuracy, supporting the suitability of this approach to quantify fungal biomass in aquatic environments.     

Multilevel Selection in Models of Prebiotic Evolution: Compartments and Spatial Self-organization

In this paper we explore the impact of new levels ofselection in models of early evolution.We contrast two types of higher levels of selection. On the one hand we look at spatially explicitmodels of replicators in which, by a process of self-organization, new levels of selection ariseas large scale spatial patterns with a dynamics of their own. Alternatively externally imposedlevels of selection above the basic replicators are created by enclosing the replicators in vesicles.In this paper we first review some results on the impact of emerging higher levels of selection onthe evolutionary persistence of interacting co-evolvingreplicator systems. Moreover, we presenta vesicle model, which can potentially integrate emerging and imposed levels of selection. We use the models to examinethe classical problem information integration in early evolution.Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1023/A:1025754907141     

Dispersal and transient dynamics in metapopulations

Abstract Recent studies of spatially explicit metapopulation models have shown the existence of complex transient behaviour (supertransients and mesotransients) characterized by spontaneous changes in the system's dynamics after thousands or hundreds of generations, respectively. Their detection in simple ecological models has been taken as evidence that transient dynamics may be common in nature. In this study, we explore the generality of these phenomena in a simple one‐dimensional spatially explicit metapopulation model. We investigate how frequently supertransient behaviour emerges in relation to the shape and type of the dispersal kernel used (normal and Laplace), system size, boundary conditions and how sensitive they are to initial conditions. Our results show that supertransients are rare, are heavily affected by initial conditions and occur for a small set of dispersal parameter values, which vary according to kernel type, system size, and boundary conditions. Similarly, mesotransients emerge over a very narrow range of dispersal parameter values and are rare under all circumstances. Thus, transient dynamics are not likely to be either common or widespread in simple models of ecological systems.     

Structure modeling of the acetylcholine receptor channel and related ligand gated channels

In this model-building study a model for the pore of the acetylcholine receptor channel is proposed. The pore is formed by five -helices of the M2 segment where three rings of hydrophilic side chains point into the channel lumen. This model is in agreement with most experimental data like photolabeling, drug affinity studies, single channel conductivity measurements and cryo electron microscopy known about this channel.This study predicts a strong coupling of the motion of the ions in the channel to that of the charged and highly hydrophilic amino acid side chains at the channel wall. Due to the negative net-charge in the pore more than a single cation may occupy the pore region. The resulting strong local electric fields make the commonly used constant field approximation obsolete for this type of ion channel.     

脑源定位技术的精度评估及其在实际中的应用

脑源定位技术旨在通过头皮表面的脑电、脑磁信号来识别大脑内的神经活动源，是研究大脑皮层神经活动、认知过程和病理功能的基础。其毫秒级的时间分辨率可以有效弥补功能核磁共振在低时间分辨率方面的不足。然而，理论分析层面中逆问题的不适定性，以及实践操作层面上不同的记录方式、电极数量和头模型构建等过程带来的误差，给脑源定位的准确性带来极大挑战，也在一定程度上限制了脑源定位方法在神经科学和心理学研究以及临床诊断治疗中的实际应用。因此，理论分析和实践操作层面中的精度评估在脑源定位方法的实际使用中至关重要。针对以上问题，本文在对现有脑源定位方法介绍的基础上，着重分析了脑源定位技术的精度评估方法以及其在基础研究和临床诊断治疗中的实际应用。具体地，本文在理论分析中总结了基于空间分辨率、基于点扩散以及串扰函数的评估方法对于不同脑源定位方法中源的重叠程度和其他源对目标源的影响；在实践操作中介绍了记录方式、电极数量和密度、头部容积传导模型等因素对源定位精度的影响；进一步介绍了脑源定位技术在时频分析、连通性分析中的应用，以及其在临床中的应用，包括癫痫、注意缺陷与多动障碍等脑部疾病。     

芸薹属自交不亲和基因的分子生物学及进化模式

芸薹属的自交不亲和性是受单基因座、复等位基因控制的孢子体控制型。自交不亲和基因座位(S-locus)是由多个基因组成的复杂区域,称之为S多基因家族,其大多数成员分布于芸薹属的整个染色体组。目前已鉴定出100多个S等位基因,它们的起源分化始于一千万年前。S-座位上存在的多基因有3种：SRK,SLG和SCR／SPII;SRK和SLG在柱头中表达,SCR／SPII在雄蕊中表达。SRK蛋白在识别同类花粉的过程中起主要作用,而SLG蛋白增强了这种自交不亲和反应。SLG与SRK基因中编码S-结构域的核苷酸序列相似性程度高达85％～98％。基因转换可能是SLG和SRK的高度同源性能够得以保持的原因。SRK,SLG和SCR基因紧密相连,并表现出高水平的序列多样性。SRK与SLG基因间的距离很近,在20～25kb之间。在柱头和花粉中,自交不亲和等位基因之间的共显性关系要比显性和隐性关系更加普遍,这是芸薹属自交不亲和性的一大特点。自交不亲和基因的进化模式存在两种假说：双基因进化模式和中性变异体进化模式;可能存在几种不同的进化方式,它们共同在自然群体中新的S等位基因进化过程中起作用。     

Local and nonlocal interactions in globular proteins and mechanisms of alcohol denaturation.

How important are helical propensities in determining the conformations of globular proteins? Using the two-dimensional lattice model and two monomer types, H (hydrophobic) and P (polar), we explore both nonlocal interactions, through an HH contact energy, as developed in earlier work, and local interactions, through a helix energy, σ. By computer enumeration, the partition functions for short chains are obtained without approximation for the full range of both types of energy. When nonlocal interactions dominate, some sequences undergo coil-globule collapse to a unique native structure. When local interactions dominate, all sequences undergo helix–coil transitions. For two different conformational properties, the closest correspondence between the lattice model and proteins in the Protein Data Bank is obtained if the model local interactions are made small compared to the HH contact interaction, suggesting that helical propensities may be only weak determinants of globular protein structures in water. For some HP sequences, varying σ/ leads to additional sharp transitions (sometimes several) and to “conformational switching” between unique conformations. This behavior resembles the transitions of globular proteins in water to helical states in alcohols. In particular, comparison with experiments shows that whereas urea as a denaturant is best modeled as weakening both local and nonlocal interactions, trifluoroethanol is best modeled as mainly weakening HH interactions and slightly enhancing local helical interactions.     

组合式3D模型在骨科临床课教学中的应用及优势

骨科是一门抽象性及实践性较强的学科,如何提高直观性和可操作性是骨科临床课教学面临的主要问题之一。3D模型技术 具有高度仿真,立体,便捷的优势能很好的再现骨骼的立体结构及三维实体信息,为解决这一问题带来了希望。笔者结合多年的 临床及教学经验,自行设计了集解剖。骨折分型及手术治疗为一体的组合式股骨颈骨折模型,在同一模型上完整的实现了知识的 整合,不仅提高了直观性和生动性更具有很好的操作性,能显著提高授课效果,其优势是目前常用的骨骼标本模型和普通单一式 模型无法比拟的。该模型于第四届全国医学院校青年教师授课基本功比赛中进行了展示并获得一等奖及最受学员欢迎奖,具有 较好的应用及推广价值。本文就组合式3D模型的制作,授课效果及优势进行了全面的阐述,希望对提高骨科临床课教学效果及 提高青年教师教学水平有一定的帮助和启发作用。     

通光散汤对小鼠哮喘模型气道高反应性和气道炎症的影响

目的观察通光散对小鼠哮喘模型气道反应和气道炎症的影响。方法35只6周龄BALB／c小鼠随机分为哮喘模型组、正常对照组和药物实验组。模型组和药物组以鸡卵白蛋白（OVA）致敏、激发;药物组在最后一次致敏后每天灌胃给予通光散汤0．72mL（相当于0．04g生药）;对照组以等体积的Ns代替OVA致敏、激发。末次激发48h后处理小鼠：无创法测定小鼠的气道高反应性,观察气道阻力变化;支气管肺泡灌洗液（BALF）行细胞学分类;观察肺组织的病理变化。结果①药物组小鼠气道阻力的变化与模型组相比明显下降,差异显著（P＜0．05）;②药物组BALF白细胞总数和Eos（％）与模型组相比明显降低（P＜0．05）。③模型组小鼠肺脏组织支气管、血管黏膜下和周围肺组织有明显的炎症细胞浸润,大量炎症细胞向支气管和血管迁移,上皮细胞部分有脱落,部分可见黏液栓,血管壁明显水肿;治疗组小鼠肺组织炎性细胞浸润和管腔黏液分泌情况较模型组明显减轻,气道粘液的分泌量得到明显的控制。结论通光散汤对小鼠哮喘模型气道高反应性和气道炎症有显著抑制作用。