Systems interface biology.

The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Hence, the interface between systems and biology is of mutual benefit to both disciplines.     

Creating biological nanomaterials using synthetic biology

Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.     

铜绿微囊藻生物钟蛋白的表达纯化与抗体制备

为了获得融合表达的铜绿微囊藻(Microcystic aeruginosa)生物钟蛋白KaiA、KaiB、KaiC并制备其相应的多克隆抗体,将kaiA、kaiB、kaiC基因分别克隆到原核表达质粒pET-His中.重组质粒pET-His-KaiA,pET-His-KaiB和pET-His-KaiC经酶切和测序鉴定后,分别转化E.coli BL21(DE3)进行融合表达.经SDS-PAGE分析可知,融合表达的KaiA、KaiB和KaiC蛋白表达量可分别达到菌体总蛋白的25%、40%和20%.经亲和层析后融合蛋白KaiA和KaiB的纯度分别达95%和92%,而KaiC经胶回收纯化后纯度也可达93%.将纯化后的三种Kai蛋白作为抗原分别免疫小鼠制备多克隆抗体,经ELISA检测抗体滴度表明,制备的抗KaiA、抗KaiB和抗KaiC的多克隆抗体效价高,分别可达到1:50000、1:60000和1:100000.Western blotting结果表明:获得的多克隆抗体具有较高的效价,抗体能识别相应的Kai蛋白,具有较高的特异性,能用于铜绿微囊藻生物钟蛋白KaiA、KaiB和KaiC的表达节律检测.     

Systems biology approaches to understanding stem cell fate choice

Stem cells have the capability to self-renew and maintain their undifferentiated state or to differentiate into one or more specialised cell types. Stem cell expansion and manipulation ex vivo is a promising approach for engineering cell replacement therapies, and endogenous stem cells represent potential drugable targets for tissue repair. Before we can harness stem cells' therapeutic potential, we must first understand the intracellular mechanisms controlling their fate choices. These mechanisms involve complex signal transduction and gene regulation networks that feature, for example, intricate feed-forward loops, feedback loops and cross-talk between multiple signalling pathways. Systems biology applies computational and experimental approaches to investigate the emergent behaviour of collections of molecules and strives to explain how these numerous components interact to regulate molecular, cellular and organismal behaviour. Here we review systems biology, and in particular computational, efforts to understand the intracellular mechanisms of stem cell fate choice. We first discuss deterministic and stochastic models that synthesise molecular knowledge into mathematical formalism, enable simulation of important system behaviours and stimulate further experimentation. In addition, statistical analyses such as Bayesian networks and principal components analysis (PCA)/partial least squares (PLS) regression can distill large datasets into more readily managed networks and principal components that provide insights into the critical aspects and components of regulatory networks. Collectively, integrating modelling with experimentation has strong potential for enabling a deeper understanding of stem cell fate choice and thereby aiding the development of therapies to harness stem cells' therapeutic potential.     

Systems approach to developmental biology – designs for robust patterning

Patterning is an important step in animal development that generates spatially non‐uniform gene expression patterns or spatially heterogeneous cellular responses. Patterning is realised by the generation and reading of positional information provided by spatial gradients of morphogens, diffusive chemicals in the extracellular environment. To achieve normal development, accurate patterning that is robust against noise is necessary. Here the authors describe how morphogen gradient formation and gradient interpretation processes are designed to achieve highly reproducible patterning. Furthermore, recent advancements in measurement and imaging techniques have enabled researchers to obtain quantitative dynamic and multi‐physical data, not only for chemical events, but also for the geometrical and mechanical properties of cells in vivo. The authors briefly review some recent studies on the effects of such non‐chemical events on patterning.Inspec keywords: biochemistry, biomechanics, genetics, zoologyOther keywords: mechanical properties, geometrical properties, chemical events, imaging techniques, measurement techniques, gradient interpretation process, morphogen gradient formation, extracellular environment, diffusive chemicals, spatial gradients, spatially heterogeneous cellular responses, gene expression patterns, animal development, robust patterning, developmental biology, systems approach     

Pressure sensitivity of the vapor-cell atomic clock

Although atomic clocks have very low levels of frequency instability, they are nonetheless sensitive (albeit slightly) to various environmental parameters, including temperature, power supply voltage, and dc magnetic fields. In the terrestrial environment, however, atmospheric pressure (i.e., the air's molecular density) is not generally included in this list, because the air's density variations near the surface of the Earth will typically have a negligible effect on the clock's performance. The situation is different, however, for clocks onboard satellites like Galileo, where manufacturing and testing are done at atmospheric pressure, while operation is in vacuum. The pressure sensitivity of atomic clocks, in particular vapor-cell atomic clocks, can therefore be of significance. Here, we discuss some of the ways in which changes in atmospheric pressure affect vapor-cell atomic clocks, and we demonstrate that, for one device, the pressure-sensitivity traces back to a pressure-induced change in the temperature of the clock's filter and resonance cells.     

Frequency equilibration in the vapor-cell atomic clock

Over the past several years, anecdotal evidence has grown indicating that Rb vapor-cell frequency standards exhibit a long "frequency equilibration" period following activation (i.e., time constant /spl sim/10/sup 2/ days). Though this long equilibration period can have important implications for diverse timekeeping systems, the mechanism driving the behavior is not well understood and has been the subject of debate. In this paper, we investigate this phenomenon for a number of Rb vapor-cell clocks with the purpose of 1) establishing the validity of frequency equilibration as a generic vapor-cell atomic clock phenomenon and 2) obtaining characteristics of the equilibration process that can be used to constrain hypothesized frequency-equilibration mechanisms. Consistent with anecdotal evidence, results on three separate manufacturers' clocks indicate that frequency equilibration is a generic vapor-cell clock phenomenon, observable in both laboratory-based and space-based systems. However, the experimental data also casts doubt on the two mechanisms most often offered to explain frequency equilibration: helium permeation through the resonance cell's glass envelope, and the intensity-dependent light-shift effect. To help guide further research, we propose two alternate mechanisms for frequency equilibration: alkali surface diffusion on the resonance-cell and lamp walls, and the spectrum-dependent light-shift effect.     

自动打铃器电路设计

介绍了LD 6 2型多功能定时模块的使用方法 ,并用其设计了简便、经济、实用的自动打铃器电路。     

Construction and evaluation of the first Brazilian atomic clock

For the past two years we have been implementing a program for the establishment of scientific time and frequency metrology in Brazil. The main objective of this program is to construct an atomic fountain and use it as a primary standard. As a first step toward this goal, we have constructed a (133)Cs beam optically pumped conventional clock. In this paper we describe the system and the results of its evaluation. The possible limitations of our short-term stability are discussed.     

Mathematical modelling of chemical clock reactions

A clock reaction is a chemical reaction which gives rise to an initial induction period before a significant concentration of one of the chemical species involved is produced. We study four closely related isothermal model reactions schemes which can exhibit clock reaction behaviour in a well-stirred situation. These reaction schemes represent a combination of quadratic or cubic autocatalysis with linear or quadratic inhibition.     

主动光钟研究进展

自2005年至今，主动光钟经过了近20年的发展。主动光钟利用原子系综作为增益介质，其受激辐射可直接作为钟激光信号。因为主动光钟工作在坏腔区域，因此具有腔牵引抑制和窄线宽两个显著的优点，可以有效克服被动光钟存在的腔长热噪声问题。由于其优越的性能，主动光钟受到了国内外同行的广泛关注。根据实现方式不同，本文将主动光钟划分为原子束型主动光钟、基于激光冷却和光晶格囚禁的主动光钟、原子束及光晶格“复合型”主动光钟、法拉第主动光钟、离子阱囚禁型主动光钟以及热原子气室型主动光钟。对于不同类型的主动光钟，本文详细介绍了其实验及理论研究进展，并分析其优劣。最后，分析了主动光钟在精密测量领域的应用并展望了主动光钟的发展方向，为推动主动光钟的广泛应用提供借鉴。     

Detection of atomic clock frequency jumps with the Kalman filter

Frequency jumps are common anomalies in atomic clocks aboard navigation system satellites. These anomalous behaviors must be detected quickly and accurately to minimize the impact on user positioning. We develop a detector for frequency jumps based on the Kalman filter. Numerical simulations show that the detector is fast, with high probability of detection and low probability of false alarms. It also has a low computational cost because it takes advantage of the recursive nature of the Kalman filter. Therefore, it can be used in applications in which little computational power is available, such as aboard navigation system satellites.     

Preliminary results of the trapped atom clock on a chip

We present an atomic clock based on the interrogation of magnetically trapped ⁸⁷Rb atoms. Two photons, in the microwave and radiofrequency domain, excite the clock transition. At a magnetic field of 3.23 G the clock transition from |F = 1, m_F = -1? to |F = 2, m_F = 1? is 1st-order insensitive to magnetic field variations. Ramsey interrogation times longer than 2 s can be achieved, leading to a projected clock stability in the low 10^-13 at 1 s for a cloud of 10⁵ atoms. We use an atom chip to cool and trap the atoms. A coplanar waveguide is integrated to the chip to carry the Ramsey interrogation signal, making the physics package as small as (5 cm)³. We describe the experimental setup and show preliminary Ramsey fringes of line width 1.25 Hz.     

Tutorial on the biology of nanotopography

The aims of this short tutorial are fourfold: 1) to introduce readers unfamiliar with the field to major concepts in the field; 2) to inform the reader of major unresolved questions; 3) to inform readers of a few major sources of relevant literature; and 4) to place the subject in relation to its relevance to other areas of science and practical application.     

Applications of viscoelastic clock models in biomechanics

The viscoelastic response of inert polymers, with respect to stress relaxation and creep, can be sped up by increasing their temperature or slowed down by decreasing their temperature. An explanation for such behavior is the existence of an internal clock whose speed relative to the laboratory clock is affected by temperature. It is assumed that the viscoelastic response of biological tissue can be affected by a biochemical factor, such as a hormone or medication, in a manner similar to that of temperature for an inert polymer. The concept of the intrinsic clock is introduced into the constitutive theory for the viscoelastic response of biological materials. Two examples are presented that illustrate the implications of a biochemically dependent internal clock: (1) cervical softening during birth due to a hormone release, (2) blood vessel dilation induced by medication.     

Evolution on neutral networks accelerates the ticking rate of the molecular clock

Large sets of genotypes give rise to the same phenotype, because phenotypic expression is highly redundant. Accordingly, a population can accept mutations without altering its phenotype, as long as the genotype mutates into another one on the same set. By linking every pair of genotypes that are mutually accessible through mutation, genotypes organize themselves into neutral networks (NNs). These networks are known to be heterogeneous and assortative, and these properties affect the evolutionary dynamics of the population. By studying the dynamics of populations on NNs with arbitrary topology, we analyse the effect of assortativity, of NN (phenotype) fitness and of network size. We find that the probability that the population leaves the network is smaller the longer the time spent on it. This progressive ‘phenotypic entrapment’ entails a systematic increase in the overdispersion of the process with time and an acceleration in the fixation rate of neutral mutations. We also quantify the variation of these effects with the size of the phenotype and with its fitness relative to that of neighbouring alternatives.     

数字钟集成电路应用及其功能扩展

本文介绍了由大规模时钟集成电路 LM85 60芯片组成的数字钟电路及其多种扩展电路 ;叙述了其在高校电子电路课程设计中应用的意义