In vitro selection of non-crosshybridizing oligonucleotides for computation

Since they minimize errors from cross-hybridizations, DNA oligonucleotides that annealas designed are beneficial to DNA computing. By in vitro selection, huge libraries of non-crosshybridizing oligonucleotides might be evolved in the test tube. As a first step, a fitness function corresponding to non-crosshybridization was based upon the duplex stability of randomly matched oligonucleotides. By melting pairs that have a low thermal stability, a protocol based on DNA polymerization selectively amplifies maximally mismatched oligonucleotides over those that were more closely matched. Experiments confirmed this property of the protocol, and in addition, a reaction temperature window was identified in which discrimination between matched and mismatched might be obtained. The protocol was iterated on a set of random starting material, and there was evidence that non-crosshybridizing libraries were in fact being created. These results are a step toward practical manufacture of very large libraries of non-crosshybridizing oligonucleotides in the test tube. This revised version was published online in June 2006 with corrections to the Cover Date.     

How ciliates manipulate their own DNA – A splendid example of natural computing

DNA computing is a novel and vivid researcharea which is genuinely interdisciplinary –computer scientists and molecular scientistscollaborate to investigate the use of DNAmolecules for the purpose of computing. DNAcomputing in vivo is the investigation ofcomputations taking place naturally in a livingcell, with the goal of understandingcomputational properties of DNA molecules intheir native environment. Gene assembly inciliates (single cell organisms) is perhaps themost involved process of DNA manipulation yetknown in living organisms. The computationalnature of this process has attracted muchattention in recent years. The resultsobtained so far demonstrate that this processof gene assembly is a splendid example ofcomputing taking place in nature, i.e., NaturalComputing. Indeed, DNA computing in vivomay be far more widespread in nature than wecurrently recognize. This paper is a tutorialon (computational nature of the) gene assemblyin ciliates, which is intended for a broadaudience of researchers interested in NaturalComputing. In particular, no knowledge ofmolecular biology is assumed on the part of themotivated reader.     

DNA计算中核酸序列设计方法比较研究

DNA计算是将现实问题进行编码,映射到DNA分子上,然后通过分子生物实验产生出代表问题解的DNA分子,最后通过检测技术提取出该DNA分子．高质量的DNA编码可以尽可能避免或减少计算过程中出现的错误,并使检测阶段易于提取出代表问题解的DNA分子．文中对基于汉明距离和基于自由能的DNA核酸编码方法进行研究,分析了两类方法的约束条件对DNA编码质量的影响,比较了两类方法排除非特异性杂交的完备性和计算量,进一步分析了两类方法编码DNA序列的效率．通过分析和比较得到,两类DNA计算编码方法都能有效地限制DNA分子间的非特异性杂交,其中基于汉明距离的DNA编码方法的计算量比较小,但是它仅能近似地估计DNA分子间杂交的热力学稳定性,不能完全替代最小自由能的编码方法．在满足DNA计算试验精度要求的条件下,采用基于汉明距离的DNA编码设计方法不仅能有效地的挑选出特异性杂交和非特异性杂交的DNA序列,还能有效地减少计算量,从而提高DNA序列设计的效率．     

DNA计算中突变误差的纠正

文章重点讨论了在DNA计算中突变误差的处理问题,其中包括突变误差的数据空间、突变误差的自动纠正和纠错码在DNA操作系统设计中的应用问题。并在分析突变误差数据空间、突变误差纠错码的基础上,提出了解决DNA计算中突变误差问题的方案。     

Automated selection of aminoglycoside aptamers

The in vitro selection of aptamers that bind to low molecular weight targets is commonly a tedious, time-consuming project. We have expanded current automated selection protocols to include aptamer selections against small molecules including the aminoglycosides neomycin, kanamycin, and tobramycin. This modified procedure decreases both the frequency of manual handling of the selection reagents and the time required to perform the experiment, generating aptamers against the chosen target at a much greater rate. Using this process, we have selected aptamers of good affinity against all three aminoglycosides chosen. The method is suitable for integration with high-throughput technologies, greatly expanding the possibility of discovering useful aptamers against other low weight targets.     

基于质粒的DNA计算模型研究

论文给出了一种基于环状质粒DNA计算的新方法,这种计算质粒包含一个特殊的插入DNA序列片断,每个片断定位在匹配的限制性内切位点,通过剪切和粘贴实现计算过程。论文同时给出了生物计算模型和相关的数学描述,这种模式的计算有待进一步研究。     

利用脱氧核酶调控基因表达的DNA计算模型研究(英文)

用于逻辑调控基因表达分子自动机的研究是DNA计算的重要研究领域．文中将脱氧核酶技术应用于DNA计算研究当中,利用脱氧核酶的特性,特别是可以作为反义药物的特点,作为构建分子自动机的主要材料,设计了调控基因H—ras表达的DNA计算模型,而且模型也可适用于其它过表达基因的调控．结合DNA计算具备的高度并行性和智能性的优点,该模型为DNA计算在基因表达调控方面的应用做了进一步探索．     

DAD计算中的遍历理论模型及算法

该文源于DNA序列杂交先后顺序的工程计算问题。在杂交先后顺序(SHB)问题中,人们试图想通过首先确定在一个很长的DNA字符串S中出现的k-长子串来了解整个原始的字符串S,通过研究k-长子串的重叠模式来重新构造原始的字符串S。该文将SHB问题转化为具体的图论问题。根据图及其线图的关系,部分解决了上述SHB问题的等价形式,即在有向线图顶点的入度和出度不超过2的情形下,用遍历理论为SHB问题建立了数学模型,从而能在多项式时间内找到有向线图的哈密顿路或圈。文章最后,指出了须进一步研究的问题。     

Language-theoretic aspects of DNA complematarity

The optimism about the possibilities of DNA computing is based on two central issues: the Watson–Crick complementarity and the massive parallelism of DNA strands. While the latter issue renders exhaustive searches possible and thus may settle problems previously considered intractable, the former issue is the cause behind the universality of many models of DNA computing. Moreover, complementarity can be viewed as a purely language-theoretic operation: undesirable circumstances in a string trigger a transition to the complementary string. This aspect of complementarity is investigated in the present paper, mainly from the point of view of L systems. New types of word sequences will be discovered. Sometimes the resulting decision problems are equivalent to well-known open problems from other areas.     

Application of Mismatch Detection Methods in DNA Computing

In many implementations of DNA computing, reliable detection of hybridization is of prime importance. We have applied several well-established DNA mutation scanning methods to this problem. Since they have been developed for speed and accuracy, these technologies are very promising for DNA computing. We have benchmarked a heteroduplex migration assay and enzymatic detection of mismatches on a 4 variable instance of 3SAT, using a previously described blocking algorithm. The first method is promising, but yielded ambiguous results. On the other hand, we were able to distinguish all perfect from imperfect duplexes by means of a CEL I mismatch endonuclease assay.     

DNA计算中荧光技术的应用及其发展

DNA计箅作为前沿科学研究的重点和热点.已经从简单发展为复杂,从理论转化为应用.在这一过程中,反应速度快、变化灵敏的荧光标记技术发挥了重要的作用.文中围绕DNA计算和荧光标记技术两个方面进行说明.一方面,对近年来DNA计算中荧光技术的应用进行了总结:(1)荧光标记的表面计算;(2)与某些切技术相结合的荧光检测;(3)与DNA链置换相结合的荧光技术;(4)与基因沉默技术相结合的荧光DNA逻辑门;(5)与DNA自组装立体结构相结合的荧光技术;(6)与DNA变构相结合的荧光技术.另一方面,介绍了几种近年来发展起来的新型荧光技术:(1)荧光信号识别放大技术;(2)与磁珠技术相结合的荧光技术;(3)与PH值变化相结合的DNA荧光技术;(4)与miRNAs检测相结合的荧光技术.在今后的研究中,只有将这两者紧密结合,才能发挥DNA计算天然的优势.     

DNA计算虚拟生物实验室设计

为了对生物实验中的反应产物进行分析、解释以及跟踪，并对实验结果进行预测，该文介绍了一个仿真生物反应的工具——虚拟生物实验室Virtual Bio—Lab（简称VBL）。在VBL中定义了一个包括聚合酶连锁反应、连接、杂交，熔化和电泳等模块在内的框架，每个模块实现一个基本的生物操作，各模块之间通过传递DNA“溶液”进行通信。使用合理的简化假设，VBL能在较短时间内实现对任意序列DNA生物操作的仿真。如有向哈密顿路径问题的DNA计算解决方案仿真。在实际应用中，VBL可以帮助验证DNA计算的理论模型，提高生物实验效率。     

DNA计算中的编码方法研究

DNA计算是一种利用生物大分子间的相互作用来实现并行计算的新的计算模式。因为其具有强大的并行性和高密度的信息存储能力,因而引起了科学界的广泛关注。编码是DNA计算的第一步,也是最重要的一步。编码质量的好坏直接影响反应过程的速度和效率。论文主要介绍了DNA计算过程中的编码问题、影响编码的因素及已有的几种主要的编码方法;最后指出了DNA计算的编码方法存在的问题及研究方向。     

DNA计算模型及应用综述

自从Adleman博士最早利用DNA计算成功求解了7个顶点有向图的Hamilton问题以来,DNA计算[1]被引入多个研究领域,成为当今科技发展的热点之一。首先介绍DNA计算的基本原理及编码方法,其次阐述了DNA计算的主要模型,再次总结了国内外研究学者应用DNA计算解决的实际问题,最后列举了DNA计算改进的相关方向。     

DNA计算的原理及研究进展

阐述了DNA计算的机理及其数学原理,介绍了Adleman实验,指出了DNA计算目前的应用领域和存在的问题,并对DNA计算的发展前景进行了展望。     

赋权图上优化问题的DNA计算方法研究

对赋权图上经典优化问题的DNA计算方法进行探讨,改进原有DNA计算模型中的权值编码方法,提出一些新的DNA编码方法及DNA算法．具体地说,通过设计赋权无向图的相对长度图给出了旅行商问题的一种相对长度DNA编码方法及DNA算法,通过设计赋权无向图的广义边图给出了中国邮递员问题的一种广义边图DNA编码方法及DNA算法,通过选取DNA序列的最佳逆补比对给出了最小生成树问题的一种基于逆补比对的DNA编码方法及DNA算法,通过设计从顶点覆盖问题到Hamilton回路问题的一种改进多项式变换给出了顶点覆盖问题的一种基于多项式变换的DNA编码方法及DNA算法．所设计的DNA计算方法提高了DNA计算中表示数值和处理数值的能力．     

并行型Ramsey数DNA计算模型

求解Ramsey数的困难在于需要搜索的解空间太大,而传统的电子计算机无法在有效的时间和存储空间上进行求解.由于DNA计算具有巨大的并行性和高密度存储能力等优点,文中研究了Ramsey数的DNA计算模型.针对传统的Ramsey数DNA计算模型存在的DNA序列量过多和序列过长的不足,利用DNA分子的特性以及生物操作将非解尽可能较早地消除,提出了并行型Ramsey数DNA计算模型,并以R(3,10)为例,给出了具体的求解步骤.     

面向网格计算的机器选择算法研究

在以网络为基础的科学与并行计算环境中,计算资源具有强分布性、异构性和动态性．当应用程序提交给网格计算环境时,需要从全部可用计算资源中选择一个资源子集以支持该应用的执行．复杂的应用问题通常包含多方面的异构性,不同性质的应用适合在不同的体系结构运行．基于对网格中可用资源的动态监测与分析结果,论文使用模糊聚类方法,根据不同的性能指标要求,为不同应用选择不同的计算结点集合．将全部可用结点划分为不同的逻辑分组,每个分组称为一个逻辑机群．针对应用的不同种类,使用λ-截矩阵为每个应用指派一个或多个聚类中心值较大的逻辑机群来协同应用调度．实验表明,根据应用类型进行机器选择,可以明显改善应用性能,通信密集应用选择内部通信性能好的逻辑机群进行调度,性能更优、计算密集应用选择计算能力强的逻辑机群进行调度,性能明显改善．     

基于粘贴DNA计算模型的分子逻辑与门的实现

理论上来说,基于DNA的分子逻辑门是DNA计算机体系结构的产生基础和DNA计算机实现技术的硬件基础。文章提出了一种新的基于粘贴DNA计算模型的分子逻辑与门的实现方法。在此方法中,逻辑门、输入信号和输出信号是DNA分子。可以实现DNA类型的逻辑门操作。需要使用包括聚合酶链反应(DNA)、琼脂糖凝胶电泳、探针的标记与检测等标准的生物工程技术。这些技术集成于DNA芯片中可用于DNA计算机的研制。     

Econometric and Statistical Computing Using Ox

This paper reviews the matrix programminglanguage Ox from the viewpoint of an econometrician/statistician.We focus on scientific programming using Ox and discussexamples of possible interest to econometricians and statisticians, such as random number generation, maximum likelihood estimation, andMonte Carlo simulation. Ox is a remarkable matrix programming language which is well suited to research and teaching in econometrics and statistics.