Construction of a genetic toggle switch in Escherichia coli

It has been proposed' that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage lambda switch and the Cyanobacteria circadian oscillator. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic toggle switch-a synthetic, bistable gene-regulatory network-in Escherichia coli and provide a simple theory that predicts the conditions necessary for bistability. The toggle is constructed from any two repressible promoters arranged in a mutually inhibitory network. It is flipped between stable states using transient chemical or thermal induction and exhibits a nearly ideal switching threshold. As a practical device, the toggle switch forms a synthetic, addressable cellular memory unit and has implications for biotechnology, biocomputing and gene therapy.     

Computational design of receptor and sensor proteins with novel functions

The formation of complexes between proteins and ligands is fundamental to biological processes at the molecular level. Manipulation of molecular recognition between ligands and proteins is therefore important for basic biological studies and has many biotechnological applications, including the construction of enzymes, biosensors, genetic circuits, signal transduction pathways and chiral separations. The systematic manipulation of binding sites remains a major challenge. Computational design offers enormous generality for engineering protein structure and function. Here we present a structure-based computational method that can drastically redesign protein ligand-binding specificities. This method was used to construct soluble receptors that bind trinitrotoluene, l-lactate or serotonin with high selectivity and affinity. These engineered receptors can function as biosensors for their new ligands; we also incorporated them into synthetic bacterial signal transduction pathways, regulating gene expression in response to extracellular trinitrotoluene or l-lactate. The use of various ligands and proteins shows that a high degree of control over biomolecular recognition has been established computationally. The biological and biosensing activities of the designed receptors illustrate potential applications of computational design.     

Distributed biological computation with multicellular engineered networks

Ongoing efforts within synthetic and systems biology have been directed towards the building of artificial computational devices using engineered biological units as basic building blocks. Such efforts, inspired in the standard design of electronic circuits, are limited by the difficulties arising from wiring the basic computational units (logic gates) through the appropriate connections, each one to be implemented by a different molecule. Here, we show that there is a logically different form of implementing complex Boolean logic computations that reduces wiring constraints thanks to a redundant distribution of the desired output among engineered cells. A practical implementation is presented using a library of engineered yeast cells, which can be combined in multiple ways. Each construct defines a logic function and combining cells and their connections allow building more complex synthetic devices. As a proof of principle, we have implemented many logic functions by using just a few engineered cells. Of note, small modifications and combination of those cells allowed for implementing more complex circuits such as a multiplexer or a 1-bit adder with carry, showing the great potential for re-utilization of small parts of the circuit. Our results support the approach of using cellular consortia as an efficient way of engineering complex tasks not easily solvable using single-cell implementations.     

基于遗传算法的组合电路最大功耗估计

用遗传算法来选择具有高功耗的输入模型,对电路进行仿真,实现组合电路的最大功耗估算。同时给出了基于统计的逻辑模拟最大功耗估计方法。基于ISCAS85基准电路的仿真表明,该方法在大规模门数时具有明显的优势,估算精度较高,且计算时间基本上电路逻辑门的线性关系。     

基于粒子群算法的数字电路测试生成

在已有的数字电路测试生成算法基础上，通过对一种结构简单且容易实现的算法——粒子群算法的研究，提出了一种基于模拟的测试矢量生成的新方法，即应用粒子群算法来进行数字电路的测试生成．对一些组合电路进行了仿真，并将其与基于遗传算法的测试生成方法进行比较，实验结果表明该方法比基于遗传算法的测试生成更为有效．     

Engineered gene circuits

A central focus of postgenomic research will be to understand how cellular phenomena arise from the connectivity of genes and proteins. This connectivity generates molecular network diagrams that resemble complex electrical circuits, and a systematic understanding will require the development of a mathematical framework for describing the circuitry. From an engineering perspective, the natural path towards such a framework is the construction and analysis of the underlying submodules that constitute the network. Recent experimental advances in both sequencing and genetic engineering have made this approach feasible through the design and implementation of synthetic gene networks amenable to mathematical modelling and quantitative analysis. These developments have signalled the emergence of a gene circuit discipline, which provides a framework for predicting and evaluating the dynamics of cellular processes. Synthetic gene networks will also lead to new logical forms of cellular control, which could have important applications in functional genomics, nanotechnology, and gene and cell therapy.     

锁相环路的相位噪声分析

本文对锁相环电路的相位噪声进行了论述,并对其中各组成部件的相位噪声也做了较为详细的分析。文中最后提出了改善锁相环相位噪声的办法。     

基于柔性免疫神经树的模拟电路故障诊断方法

模拟电路的非线性特性、连续性和元器件的容差等因素给故障的建模分析造成了诸多不确定因素,因此其智能故障诊断方法的研究至关重要。柔性神经树是一种采用树形结构和一组运算符集合构成的新型神经网络,与传统神经网络相比具有更加灵活的自动优化能力。本文将人工免疫机理融入柔性神经树,提出了一种基于柔性免疫神经树的模拟电路故障诊断方法。通过对一种典型模拟电路的故障诊断仿真试验,证明了该方法的有效性和可行性。     

合成生物学:学科基础、研究进展与前景展望

由于基因组测序及DNA合成技术与工具的突破性进展,生物工程正在加速发展,导致合成生物学的出现。本文介绍了合成生物学的定义,强调了该学科的工程属性及关键的工程研究方法,举例说明了最近几年合成生物学在生物科学知识产生,在生物零件、装置及系统的建造,以及在药物、能源、酶的生产等研究领域的重要进展。特别值得注意的是,这些进展中的许多技术被认为是能够改变世界的技术,是由35岁以下甚至30岁以下的年轻研究人员完成的。本文还展望了合成生物学在生物科学和生物经济中的巨大潜力,也指出其面临的科学技术难题以及在生物安全、伦理、知识产权方面的问题。     

一种数字电路的桥接故障诊断方法

针对目前数字电路桥接故障诊断效率低的问题,提出了一种基于微分故障模拟算法的数字电路的桥接故障诊断方法,用VHDL语言对电路模型进行了重新建模,利用单固定故障的信息来诊断桥接故障,并对ISCAS85平台下的一些电路进行了模拟,结果表明该方法简单、高效,特别适合于数字电路的故障诊断,对于提升我国数字电路可靠性具有重要的理论意义与实际推广应用价值。     

遗传算法在立体图象匹配中的应用

基于传统立体图象匹配技术,提出了一种新的使用遗传算法的特征匹配方法．实验中,采用了两种特征提取算法,以适应不同图象要求．实验用图包括自然景物图和人工合成图．此外,用ＢｒａｎｃｈＡｎｄＢｏｕｎｄ算法得出比较结果．实验结果表明,遗传算法有好的匹配正确率和收敛速度,具有鲁棒性,适合立体图象匹配．     

Channel plasmon subwavelength waveguide components including interferometers and ring resonators

Photonic components are superior to electronic ones in terms of operational bandwidth, but the diffraction limit of light poses a significant challenge to the miniaturization and high-density integration of optical circuits. The main approach to circumvent this problem is to exploit the hybrid nature of surface plasmon polaritons (SPPs), which are light waves coupled to free electron oscillations in a metal that can be laterally confined below the diffraction limit using subwavelength metal structures. However, the simultaneous realization of strong confinement and a propagation loss sufficiently low for practical applications has long been out of reach. Channel SPP modes--channel plasmon polaritons (CPPs)--are electromagnetic waves that are bound to and propagate along the bottom of V-shaped grooves milled in a metal film. They are expected to exhibit useful subwavelength confinement, relatively low propagation loss, single-mode operation and efficient transmission around sharp bends. Our previous experiments showed that CPPs do exist and that they propagate over tens of micrometres along straight subwavelength grooves. Here we report the design, fabrication and characterization of CPP-based subwavelength waveguide components operating at telecom wavelengths: Y-splitters, Mach-Zehnder interferometers and waveguide-ring resonators. We demonstrate that CPP guides can indeed be used for large-angle bending and splitting of radiation, thereby enabling the realization of ultracompact plasmonic components and paving the way for a new class of integrated optical circuits.     

A sensing array of radically coupled genetic 'biopixels'

Although there has been considerable progress in the development of engineering principles for synthetic biology, a substantial challenge is the construction of robust circuits in a noisy cellular environment. Such an environment leads to considerable intercellular variability in circuit behaviour, which can hinder functionality at the colony level. Here we engineer the synchronization of thousands of oscillating colony 'biopixels' over centimetre-length scales through the use of synergistic intercellular coupling involving quorum sensing within a colony and gas-phase redox signalling between colonies. We use this platform to construct a liquid crystal display (LCD)-like macroscopic clock that can be used to sense arsenic via modulation of the oscillatory period. Given the repertoire of sensing capabilities of bacteria such as Escherichia coli, the ability to coordinate their behaviour over large length scales sets the stage for the construction of low cost genetic biosensors that are capable of detecting heavy metals and pathogens in the field.     

Accurate whole human genome sequencing using reversible terminator chemistry

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.     

一种新型的基因编码与基因算法

研究和发展模仿生物体行为和功能的计算理论和方法是现代信号与信息处理领域非常迷人的方向之一,神经计算和基因计算正是在这一方向上的杰作。科学家们至今对生物进化复杂性和脑功能复杂性的理解还很不全面和深入,但是人们模仿其机制的计算在许多工程应用问题中已取得良好的效果。本文论述了生物体的基因编码和译码的基本原理,据此提出了基因计算的新框架和途径。     

模拟电路故障诊断的一种系统方法

提出了模拟电路故障诊断和定位的一种系统理论方法。该方法不受电路规模和复杂程度的限制，可确定电路中哪些元件故障，辨识出故障元件参数值。测后主要解低阶线性方程，计算量小。实例表明，方法可靠。     

Analog Module Placement Design Using Genetic Algorithm

This paper presents a novel genetic algorithm for analog module placement based on a generalization of the two-dimensional bin packing problem. The genetic encoding and operators assure that all problem constraints are always satisfied. Thus the potential problems of adding penalty terms to the cost function are eliminated so that the search configuration space is drastically decreased. The dedicated cost function is based on the special requirements of analog integrated circuits. A fractional factorial experiment was conducted using an orthogonal array to study the algorithm parameters. A meta-GA was applied to determine the optimal parameter values. The algorithm was tested with several local benchmark circuits. The experimental results show that the algorithm has better performance than the simulated annealing approach with satisfactory results comparable to manual placement. This study demonstrates the effectiveness of the genetic algorithm in the analog module placement problem. The algorithm has b     

基于遗传算法的可进化模拟滤波器的实现

以遗传算法和可编程模拟器件ispPAC80为评估手段和载体，实现了可进化的模拟滤波器的设计，将遗传算法和可编程模拟器件相结合，可在无须改动硬件的情况下。实现转折频率和阻带衰减等滤波参数的变换(即可进化性)，其性能达到甚至超过经典的同阶滤波器。     

电力电子电路机理仿真实验系统的初步研究

把建立电路方程的一般方法-表矩阵法,应用于带开关器件的电力电子电路,通过把电路中的开关元件视为理想开关,并将其作为一个电路元件包含在电路中,建立起统一的电路方程,采用向后欧拉法对其进行数值求解.电路的表矩阵方程的系数矩阵通常是稀疏矩阵,需要采用稀疏矩阵技术进行计算机仿真.最后用一个实例,单象限降压型电路(Buck电路)的仿真,说明了这种方法在实际应用中的可行性和有效性.