Computer-assisted design for scaling up systems based on DNA reaction networks

In the past few years, there have been many exciting advances in the field of molecular programming, reaching a point where implementation of non-trivial systems, such as neural networks or switchable bistable networks, is a reality. Such systems require nonlinearity, be it through signal amplification, digitalization or the generation of autonomous dynamics such as oscillations. The biochemistry of DNA systems provides such mechanisms, but assembling them in a constructive manner is still a difficult and sometimes counterintuitive process. Moreover, realistic prediction of the actual evolution of concentrations over time requires a number of side reactions, such as leaks, cross-talks or competitive interactions, to be taken into account. In this case, the design of a system targeting a given function takes much trial and error before the correct architecture can be found. To speed up this process, we have created DNA Artificial Circuits Computer-Assisted Design (DACCAD), a computer-assisted design software that supports the construction of systems for the DNA toolbox. DACCAD is ultimately aimed to design actual in vitro implementations, which is made possible by building on the experimental knowledge available on the DNA toolbox. We illustrate its effectiveness by designing various systems, from Montagne et al.''s Oligator or Padirac et al.''s bistable system to new and complex networks, including a two-bit counter or a frequency divider as well as an example of very large system encoding the game Mastermind. In the process, we highlight a variety of behaviours, such as enzymatic saturation and load effect, which would be hard to handle or even predict with a simpler model. We also show that those mechanisms, while generally seen as detrimental, can be used in a positive way, as functional part of a design. Additionally, the number of parameters included in these simulations can be large, especially in the case of complex systems. For this reason, we included the possibility to use CMA-ES, a state-of-the-art optimization algorithm that will automatically evolve parameters chosen by the user to try to match a specified behaviour. Finally, because all possible functionality cannot be captured by a single software, DACCAD includes the possibility to export a system in the synthetic biology markup language, a widely used language for describing biological reaction systems. DACCAD can be downloaded online at http://www.yannick-rondelez.com/downloads/.     

Quantum metabolism explains the allometric scaling of metabolic rates

A general model explaining the origin of allometric laws of physiology is proposed based on coupled energy-transducing oscillator networks embedded in a physical d-dimensional space (d = 1, 2, 3). This approach integrates Mitchell''s theory of chemi-osmosis with the Debye model of the thermal properties of solids. We derive a scaling rule that relates the energy generated by redox reactions in cells, the dimensionality of the physical space and the mean cycle time. Two major regimes are found corresponding to classical and quantum behaviour. The classical behaviour leads to allometric isometry while the quantum regime leads to scaling laws relating metabolic rate and body size that cover a broad range of exponents that depend on dimensionality and specific parameter values. The regimes are consistent with a range of behaviours encountered in micelles, plants and animals and provide a conceptual framework for a theory of the metabolic function of living systems.     

Biomolecular implementation of linear I/O systems

Linear I/O systems are a fundamental tool in systems theory, and have been used to design complex circuits and control systems in a variety of settings. Here we present a principled design method for implementing arbitrary linear I/O systems with biochemical reactions. This method relies on two levels of abstraction: first, an implementation of linear I/O systems using idealised chemical reactions, and second, an approximate implementation of the ideal chemical reactions with enzyme-free, entropy-driven DNA reactions. The ideal linear dynamics are shown to be closely approximated by the chemical reactions model and the DNA implementation. We illustrate the approach with integration, gain and summation as well as with the ubiquitous robust proportional-integral controller.     

Memory-endowed US cities and their demographic interactions

A quantitative understanding of cities'' demographic dynamics is becoming a potentially useful tool for planning sustainable growth. The concomitant theory should reveal details of the cities'' past and also of its interaction with nearby urban conglomerates for providing a reasonably complete picture. Using the exhaustive database of the Census Bureau in a time window of 170 years, we exhibit here empirical evidence for time and space correlations in the demographic dynamics of US counties, with a characteristic memory time of 25 years and typical distances of interaction of 200 km. These correlations are much larger than those observed in a European country (Spain), indicating more coherent evolution in US cities. We also measure the resilience of US cities to historical events, finding a demographical post-traumatic amnesia after wars (such as the American Civil War) or economic crisis (such as the 1929 Stock Market Crash).     

Imaging microstructure and stress fields within a cross-ply composite laminate

Microfocus X-ray diffraction can be used in a scanning acquisition mode to image a fibre reinforced composite material in terms of a range of different parameters. This includes microstructural information, as well as detail of emerging stress fields around open hole geometries. In this study, the in situ deformation of a cross-ply laminate specimen is investigated. The results show a number of interesting phenomena related to stress transfer in such systems. This includes stress concentrations in fibres adjacent to the open hole and local shear forces acting upon fibres perpendicular to the deformation axis. In addition to imaging the sample, the technique also allows a number of mechanical parameters to be estimated. This includes transverse strain and longitudinal stiffness. Using isotropic elasticity theory, the stress concentration tangential to the open hole can be determined analytically.     

Electron tomography: An imaging method for materials deformation dynamics

The combination of in-situ and three-dimensional (3D) in transmission electron microscopy (TEM) is one of the emerging topics of recent advanced electron microscopy research. However, to date, there have been only handful examples of in-situ 3D TEM for material deformation dynamics. In this article, firstly, the authors briefly review technical developments in fast tilt-series dataset acquisition, which is a crucial technique for in-situ electron tomography (ET). Secondly, the authors showcase a recent successful example of in-situ specimen-straining and ET system development and its applications to the deformation dynamics of crystalline materials. The system is designed and developed to explore, in real-time and at sub-microscopic levels, the internal behavior of polycrystalline materials subjected to external stresses, and not specifically targeted for atomic resolution (although it may be possible). Technical challenges toward the in-situ ET observation of 3D dislocation dynamics are discussed for commercial structural crystalline materials, including some of the early studies on in-situ ET imaging and 3D modeling of dislocation dynamics. A short summary of standing technical issues and a proposed guideline for further development in the 3D imaging method for dislocation dynamics are then discussed.     

Vortex�CAntivortex Dynamics in a Mesoscopic Superconducting Prism with a Centered Antidot

In this work, we investigated theoretically the dynamics of the annihilation of a vortex?Cantivortex pair in a superconducting mesoscopic prism of square transversal section with a square antidot inserted at its center. The sample is immersed in a magnetic field applied perpendicular to the sample plane. It is assumed that the inner hole is made of a material whose properties are accounted on de Gennes boundary conditions via de Gennes extrapolation length (b parameter). We analyze the nucleation of vortices and antivortices by increasing the magnetic field from zero until the first vortex is created and then reversing the polarity of the applied magnetic field until an antivortex is also created. Depending on the b parameter, the vortex?Cantivortex encounter can take place at the hole or at the superconducting region around it. In the framework of the time dependent Ginzburg?CLandau theory, we calculate the magnetization, order parameter topology, the position and the velocity of the vortex and antivortex singularities as a function of time.     

引入传递矩阵法的复杂多体系统连接件建模方法研究

摘 要：以复杂系统动力学建模为研究背景,在计算多体系统动力学理论指导下,提出引入传递矩阵法模拟连接件的建模方法。以柴油机机脚螺栓为例使用该方法进行建模分析,结果表明引入传递矩阵法的复杂多体系统连接件建模和分析是可行的,在不失复杂系统整体动力学特性的前提下较精确地融入了连接件的传递特性,调谐了大零部件和小连接件间耦合建模时所建立矩阵的奇异性,具有求解速度快、模型数据量小等优点。文中的建模方法给建立柴油机整机振动与抗冲击快速评估模型奠定了一定基础。     

Delayed self-regulation and time-dependent chemical drive leads to novel states in epigenetic landscapes

The epigenetic pathway of a cell as it differentiates from a stem cell state to a mature lineage-committed one has been historically understood in terms of Waddington''s landscape, consisting of hills and valleys. The smooth top and valley-strewn bottom of the hill represent their undifferentiated and differentiated states, respectively. Although mathematical ideas rooted in nonlinear dynamics and bifurcation theory have been used to quantify this picture, the importance of time delays arising from multistep chemical reactions or cellular shape transformations have been ignored so far. We argue that this feature is crucial in understanding cell differentiation and explore the role of time delay in a model of a single-gene regulatory circuit. We show that the interplay of time-dependent drive and delay introduces a new regime where the system shows sustained oscillations between the two admissible steady states. We interpret these results in the light of recent perplexing experiments on inducing the pluripotent state in mouse somatic cells. We also comment on how such an oscillatory state can provide a framework for understanding more general feedback circuits in cell development.     

Electrochemical investigation of dopamine at the water/1,2-dichloroethane interface

Dopamine is an important neurotransmitter in mammalian central and peripheral nervous systems and is also a medicament to cure some neuropsychosis. In this work, ion transfer (IT), facilitated ion transfer (FIT) of protonated dopamine, and electron transfer (ET) between dopamine and ferrocene are investigated at the water/1,2-dichloroethane (W/DCE) interface. The IT and FIT reactions of protonated dopamine can be observed simultaneously within the same potential window. The experimental results demonstrate that dibenzo-18-crown-6, dibenzo-24-crown-8, and benzo-15-crown-5 work well with the protonated dopamine. The amperometric detection of dopamine based on either the IT or the FIT of protonated dopamine can get rid of the interference of ascorbic acid, and the lowest concentration that can be determined is approximately 0.05 microM by differential pulse voltammetry. For the ET reaction, its kinetics can be evaluated by scanning electrochemical microscopy, and the results show that the relationship between rate constants and driving force at the unmodified W/DCE interface obeys the Butler-Volmer equation in a rather wide potential region. When the W/DCE interface is modified by egg lecithin, the ET rate constants decrease with increasing concentration of egg lecithin, which indicates that egg lecithin hinders the ET reaction. When the driving force is increased to a certain degree, the linear relationship between ET rate constants and the driving force is distorted. These results will be helpful to understand both the pharmacodynamics and the neural signal transmission mechanism of dopamine at biological membranes and also provide a novel way to detect dopamine.     

Delayed Photoelectron Transfer in Pt‐Decorated CdS Nanorods under Hydrogen Generation Conditions

Noble‐metal‐decorated colloidal semiconductor nanocrystals are currently receiving significant attention for photocatalytic hydrogen generation. A detailed knowledge of the charge‐carrier dynamics in these hybrid systems under hydrogen generation conditions is crucial for improving their performance. Here, a transient absorption spectroscopy study is conducted on colloidal, Pt‐decorated CdS nanorods addressing this issue. Surprisingly, under hydrogen generation conditions (i.e., in the presence of the hole‐scavenger sodium sulfite), photoelectron transfer to the catalytically active Pt is slower than without the hole scavenger, where no significant hydrogen generation occurs. This unexpected behavior can be explained by different degrees of localization of the electron wavefunction in the presence and absence of holes on the nanorods, which modify the electron transfer rates to the Pt. The results show that solely optimizing charge transfer rates in photocatalytic nanosystems is no guarantee of improved performance. Instead, the collective Coulomb interaction‐mediated electron–hole dynamics need to be considered.     

Quantum Interference Effects in p-Si1−x Ge x Quantum Wells

Quantum interference effects, such as weak localization and electron-electron interaction (EEI), have been investigated in magnetic fields up to 11 T for hole gases in a set of Si_1?x Ge _x quantum wells with 0.13<x<0.95. The temperature dependence of the hole phase relaxation time has been extracted from the magneto-resistance between 35 mK and 10 K. The spin-orbit effects that can be described within the Rashba model were observed in low magnetic fields. A quadratic negative magneto-resistance was observed in strong magnetic fields, due to the EEI effect. The hole-phonon scattering time was determined from hole overheating in a strong magnetic field.