抑癌基因p53密码子偏好性分析及其突变致癌预测

p53是人类恶性肿瘤中最常见的突变基因,与人类肿瘤的发生相关性最高,也是基因研究中热度最高的基因之一。为深入研究人类p53基因突变机理,选取了6条人类p53基因mRNA序列。首先,利用基于RSCU方法下的多重变量分析软件CodonW对影响密码子使用的各项参数进行计算和统计分析,分析可得,密码子适应指数(CAI)与最优密码子使用频率(FOP)、密码子偏爱指数(CBI)均呈极显著正相关(p<0.01);有效密码子数(ENC)与密码子偏爱指数(CBI)、GC含量、GC3s、最优密码子使用频率(FOP)、第三位碱基G3s、密码子适应指数(CAI)均呈极显著负相关(p<0.01)。然后,再利用QRSCU编码方法,对p53密码子偏好性间距进行了分析设计,得出了基于拟氨基酸编码的方法能充分体现p53密码子对同义密码子的一致偏好性的结论,且p53基因更偏好使用以c或g结尾的同义密码子。以上各项参数也充分验证了拟氨基酸编码方法与p53密码子偏好性研究结果的紧密关联性。最后,结合前人对抑癌基因p53突变致癌的研究,对该6条基因序列作了病变预测,从而为人类恶性肿瘤的预防和预测提供重要的理论依据。     

人类p53肿瘤蛋白的偏好性分析及其应用*

为了深入研究人类p53肿瘤蛋白,对七条最新的人类p53肿瘤蛋白的mRNA序列的偏好性及其同源性进行了分析。利用MEGA4.0（molecular evolutionary genetics analysis）软件的Distance功能得到七条基因的mRNA序列及其相应的蛋白质序列的同源性,并通过比较它们的RSCU和QRSCU值,对p53基因发生突变时偏好使用同义密码子的情况进行了分析。研究结果表明,基于拟氨基酸编码方法能更明显地展示出它们对同义密码子的一致偏好性,并且p53基因发生突变时偏好使用以c/g结     

基于对应分析的密码子用法可视化研究

密码子用法可以简介为物种、基因组、基因或序列集中64种密码子的使用方式。密码子用法的可视化为研究样本的密码子用法特征、不同样本间的密码子偏好,提供了1种直观、有效的图形化手段。可基于多种参数的对应分析(CA)法是其中1种重要的可视化方法。在本文中,以果蝇、人类、拟南芥、酿酒酵母、线虫、大肠杆菌、枯草芽孢杆菌及除虫链霉菌8个物种的密码子用法数据为例,通过比较密码子实际出现次数(Number)、密码子用法频率(F1000)、密码子用法分值(Fraction)、相对适应度(RA)与相对同义密码子用法(RSCU)5种参数的可视化结果,得到如下初步结论:(1)不论采用5种参数中的哪1种,65维(一维物种+64维密码子)的数据都可通过CA降维为7维,而此时的累计惯量为100%,即完全还原原数据集中的所有信息;(2)采用密码子平均用法(F1000)是1个较好的选择,其前二维的累计惯量可以达到83.6%,但是基于Fraction可以获得更高的累计惯量,达到85.1%,Number、RSCU次之,在考虑计算量的情况下,选择Number也可以获得失真度较小的结果,RA参数的最低,仅有76.9%。     

As~(3+)与DNA4种碱基相互作用的理论研究

砷在进入生物体后,可通过对基因损伤和基因表达等多方面的影响而发挥其毒性。本文运用量子化学计算,研究了As3+与DNA4种碱基的配位作用。从理论上确立了As3+与4种碱基的配合特征和各种配合物的相对稳定性以及As3+对4种碱基配合的选择性。当As3+与碱基结合时,最多能与3个碱基配体形成稳定构型,我们共得到17个稳定的三配体配合物。其中,As3+与O和N所形成配位键As-O和As-N的键长范围分别为(1.76~1.85)?和(1.88~2.01)?。As3+与4种不同碱基作用时,倾向与鸟嘌呤发生配位反应,且易于结合位点羰基O处发生反应。     

密码子用法数据库辅助工具CUDassist的开发

密码子用法的研究是遗传密码的进化、基因的水平转移、基因表达的调控和异源表达的优化等领域不可或缺的内容.2个重要的密码子用法在线服务密码子用法数据库(CUD)和图形化密码子用法分析器(GCUA)为研究者提供了有力的数据支持,但仍存在一些问题,如密码子用法数据库可接受的检索方式过于单一,在特定密码子用法表(CUT)中Fraction参数值显示有误,图形化密码子用法分析器仪提供2个密码子用法表的比对视图等.本文针对这些问题,研发了密码子用法数据库辅助工具"CUDassist",做出4个改进: (1)增加密码子用法数据库的可检索方式;(2)修正密码子用法数据库中Fraction值显示错误的问题;(3)在密码子用法表中直接给出相对适应度(RA)参数值;(4)提供多个密码子用法表的比对视图.从而为研究者提供更方便、准确和丰富的密码子用法的信息,并在一定程度上有效融合了密码子用法数据库和图形化密码子用法分析器的功能,实现一站式服务.     

基于数据密码子的异常入侵检测系统的研究

文章以基因工程中的基因密码子的作用机理作为理论仿真基础,利用生物免疫学中的一种全新的免疫模式——危险模式,来建立起一个基于数据密码子的系统调用异常入侵检测系统。该系统克服了传统免疫算法的计算规模庞大、特征复杂、自适应进化能力差等缺点。     

基于累积前景理论的大群体风险型动态应急决策方法

针对复杂环境下决策者对于应急事件作出的决策往往会面对偏好转移的问题,提出一种新的大群体风险型动态应急决策方法.首先利用偏好判断矩阵对全体决策者偏好进行聚类分析和偏好集结;其次,利用累积前景理论计算决策大群体的总体前景值;再次,考虑未来状态转移链,经过多轮调整得出决策者偏好转移矩阵,结合偏好转移矩阵和大群体总体前景值可得到当前突发事件状态下的最优方案;最后,通过案例分析与对比表明所提出方法的有效性和可行性.     

结合用户主观偏好与项目属性扩充的推荐算法

协同过滤算法是推荐系统中使用广泛的一种算法,然而传统协同过滤算法仅利用评分信息,实际场景下会面临相似度计算准确率低,推荐个性化程度不高的缺陷,难以满足用户的需求.针对协同过滤算法的不足,结合用户主观偏好与项目属性扩充提出一种改进算法,首先在项目相似度计算上做了两个改进:引入标签相关度,依据项目标签相关度来研究项目之间的相似度,并根据项目历史评分用户的特征构造项目的扩充属性,可用于从项目受众类型的角度衡量项目相似度;其次考虑到用户存在主观偏好的情况,使用支持向量机为每个用户训练标签偏好预测模型,可用于项目预测评分的修正,提高推荐的个性化程度和准确度.基于MovieLens数据集的实验结果表明,所提算法能更准确地计算项目间的相似度,且能根据用户的个性化偏好得出更精确的预测评分.     

用多种统计特征识别基因序列

基于统计特征的基因识别算法对较长的序列预测精度较高,但对于较短的基因序列识别精度仍然不理想。在分别研究基因序列的碱基组成成分、周期3性质、密码子使用频率和碱基位置相关性的基础上,提出了一种基于多种特征的基因识别算法。实验结果表明对于长度小于90 bp（base pair）的基因序列,提出算法的平均预测精度比现有算法提高2.2％。     

开发可统计任意密码子用法的软件BestCodon

密码子偏好是自然现象,分析密码子的用法可以优化表达基因,即密码子优化,从而调节目的基因在特定宿主中的表达水平。现有密码子用法分析软件多数只限于单个密码子,适用于密码子对和密码子三联体的较少见。本文提出1种可统计任意密码子用法的软件结构,开发出1个密码子用法统计软件BestCodon,拥有序列检查和密码子用法统计2个模块。检查模块可代替人工校对,剔除输入序列中非规范字符,为后续分析提供正确的、符合规范的数据。统计模块根据用户指定的密码子组合类型,结果返回特定的密码子用法表。本文还探讨序列检查和密码子用法统计中计算机的运算特性,结果表明该软件检查1条长达150000 bp的序列仅耗时约0.2 s,而从中统计密码子十联体的用法仅耗时约0.1 s。     

CodonO: a new informatics method for measuring synonymous codon usage bias within and across genomes

Codon usage bias reveals the silent molecular evolution pattern. Previous research showed the codon usage bias was associated with many biological processes, such as protein expression level, genetic coding error minimization, mRNA stability, codon context, tRNA richness, CpG suppression, DNA methylation, and tissue or organ specificity. In this paper we reviewed major methods of codon usage bias measurement. Since most of existing methods are only suitable for the comparison of codon usage bias within a single genome, we introduced a new informatics index, referred to as synonymous codon usage order (SCUO), to measure synonymous codon usage bias within and across genomes. In this method, Shannon informational theory was applied to describe the SCUO of each gene using a value ranging from 0 to 1, with larger values associated with greater codon usage bias. We compared our method with the codon adaptation index (CAI) method for measuring codon bias in Escherichia coli and Sacharomyces cerevisiae. We also studied the correlation between SCUO and CAI, and the relation of SCUO with gene length, gene function, and GC composition. In addition, we explored the correlation between SCUO and mRNA abundance in S. cerevisiae using SAGE expression data. The software package codonO is freely available at http://digbio.missouri.edu/～wanx/cu/codonO/.     

Phases of functional, near-normoglycaemic insulin substitution: what are computers good for in the rehabilitation process in type I (insulin-dependent) diabetes mellitus?

We have divided the rehabilitation process in patients with insulin-dependent diabetes mellitus into the following four phases. The basic phase, the so-called 'phase 0', provides information about literature, different strategies of treatment and introduces the use of regular insulin as well as blood sugar self-monitoring. During 'phase 1' (i.e. 'diabetes education common sense') all the initial information from 'phase 0' will be used practically and discussed in depth. After the patient's actual insulin need (U/24 h) has been estimated, initial algorithms for functional insulin use can be defined. And this is the turning point to 'phase 2' of the group rehabilitation process, the so-called education in functional insulin use. Initial algorithms should be understood as a preliminary answer to the patient's questions, 'What is my basal insulin need?', 'How much insulin do I need for a particular amount of carbohydrates?', and 'What is the hypothetical response of my blood glucose to a particular amount of insulin?'. These algorithms are going to be used and optimised now by the patient (under the supervision of the physician) during the so-called 'insulin games' (fasting or 24 h, experimental violation of traditional dietary rules, etc.) to demonstrate (1) how to influence actual glycaemia through immediate correction of blood sugar off blood sugar target (primary adjustment of insulin dosing), and (2) how to optimise algorithms for insulin use (secondary insulin adjustment) in future conditions of different insulin sensitivity. The 'phase 3' of individual teaching is an ongoing process of updating the patient's knowledge and practical skills.(ABSTRACT TRUNCATED AT 250 WORDS)     

自然语言水印隐蔽性自动评测方法

对自然语言水印(NLW)隐蔽性评测的缺乏严重影响了该领域技术的发展,为此,结合NLW的特点和语言心理学,以人类对语言释义的速度及难易程度为依据,提出了NLW隐蔽性的感知模型和相应的评测方案：从语法错误、搭配错误和语义损失三个方面对隐蔽性进行评测。最后,针对四种不同水印技术(基于绝对同义词替换的T-Lex水印系统、相对同义词替换水印系统、基于句法树的水印系统和中文句法水印系统),一方面利用该方案进行自动评测,另一方面进行置信度为90%的人工评测。两种方法得到了相同的结论：基于词汇的NLW技术的隐蔽性优于基于句子的NLW技术,说明该自动评测方法是评测NLW隐蔽性的有效评测方法。     

Relative attitude formation control of multi‐agent systems

This paper investigates the relative attitude formation control problem for a group of rigid‐body agents using relative attitude information on SO(3). On the basis of the gradient of a potential function, a family of distributed angular velocity control laws, which differ in the sense of a geodesic distance dependent function, is proposed. With directed and switching interaction topologies, the desired relative attitude formation is showed to be achieved asymptotically provided that the topology is jointly quasi‐strongly connected. Moreover, several sufficient conditions for the desired formation to be achieved exponentially and almost globally are given. Additionally, numerical examples are provided to illustrate the effectiveness of the proposed distributed control laws. Copyright © 2017 John Wiley & Sons, Ltd.     

基于谐振型SAW传感器的呼吸检测系统设计

人呼吸中VOCs的种类及含量与人的身体状况有关,对其的检测可用于疾病的诊断.本研究利用谐振型声表面波传感器,开发出一套可用于对人呼吸中VOCs进行检测的系统.本文首先介绍了该系统的组成及原理,并对系统的关键环节进行了测试.在此基础上,系统对多组测试样本进行了实验,实验结果初步表明,本系统可对×10-9(ppb)级的VO...     

Monotonic convergence and robustness of higher‐order gain‐adaptive iterative learning control

For a class of repetitive linear discrete time‐invariant systems with higher relative degree, a higher‐order gain‐adaptive iterative learning control (HOGAILC) is developed while minimizing the energy increment of two adjacent tracking errors with the argument being the iteration‐time‐variable learning‐gain vector (ITVLGV). By taking advantage of rows/columns exchanging transformation of matrix, the ITVLGV is achieved in an explicit form which is dependent upon the system Markov parameters and adaptive to the iterationwise tracking‐error vector. Algebraic derivation demonstrates that the HOGAILC is strictly monotonously convergent. On the basis of the adaptive mode, a damping quasi‐HOGAILC strategy is exploited while the uncertainties of the system Markov parameters exist. Rigorous analysis delivers that the damping quasi‐scheme is strictly monotonically convergent and thus the HOGAILC mechanism is robust to a wider range of uncertainty of system parameters and the damping factor may relax the uncertainty range. Numerical simulations are made to illustrate the validity and the effectiveness.     

基于一种相对Hamming距离的入侵检测方法--RHDID

首先分析了传统入侵检测方法的不足,即误用入侵检测方法难于检测新形式的入侵,异常入侵检测方法难于建立合理有效的正常行为特征和检测方法。然后,通过对特权进程的系统调用和参数序列的研究,提出了一种相对Hamming距离入检测方法（RHDID）。应用RHDID检测入侵不仅能有效降低漏报率和误报率,而且使实时入侵检测成为可能。最后,原型系统证实了该方法的可行性,获得了在实时环境中检测入侵的技术效果。     

Construction of modified embedded atom method potentials for the study of the bulk phase behaviour in binary Pt–Rh, Pt–Pd, Pd–Rh and ternary Pt–Pd–Rh alloys

A first attempt is made to simulate the solid part of the phase diagram of the ternary Pt–Pd–Rh system. To this end, Monte Carlo (MC) simulations are combined with the Modified Embedded Atom Method (MEAM) and optimised parameters entirely based on Density Functional Theory (DFT) data. This MEAM potential is first validated by calculating the heat of mixing or the demixing phase boundary for the binary subsystems Pt–Rh, Pt–Pd and Pd–Rh. For the disordered alloy systems Pt–Rh and Pt–Pd, the MC/MEAM simulation results show a slightly exothermic heat of mixing, thereby contradicting any demixing behaviour, in agreement with other theoretical results. For the Pd–Rh system the experimentally observed demixing region is very well reproduced by the MC/MEAM simulations. The extrapolation of the MEAM potentials to ternary systems is next validated by comparing DFT calculations for the energy of formation of ordered Pt–Pd–Rh compounds with the corresponding MEAM energies. Finally, the validated potential is used for the calculation of the ternary phase diagram at 600 K.     

Exponential quasi‐(Q,S,R)‐dissipativity and practical stability for switched nonlinear systems

In this paper, the problems of exponential quasi‐(Q,S,R)‐dissipativity and practical stability analysis for a switched nonlinear system are addressed. First, the concept of exponential quasi‐(Q,S,R)‐dissipativity for switched nonlinear systems without requiring the exponential quasi‐(Q,S,R)‐dissipativity property of each subsystem is proposed. Then, we show that an exponentially quasi‐(Q,S,R)‐dissipative switched nonlinear system is practically stable. Second, this exponential quasi‐(Q,S,R)‐ dissipativity property for a switched nonlinear system is obtained by the design of a state‐dependent switching law. Third, a composite state‐dependent switching law is designed to render the feedback interconnection of switched nonlinear systems exponentially quasi‐(Q,S,R)‐dissipative. This switching law allows interconnected switched nonlinear systems to switch asynchronously. Finally, the effectiveness of the results is verified by a numerical example.