WorldWideScience

Sample records for gene circuit dynamics

  1. Dynamically Tunable Memory in Two-Component Gene Circuit

    Energy Technology Data Exchange (ETDEWEB)

    Ghim, C; Almaas, E

    2008-09-05

    Cell has the potential to remember the environmental conditions for many (10{sup 7}) generations but stochastic fluctuations set a fundamental limit on the stability of this memory. Here we explicitly take the binding-unbinding of macromolecules into account to propose a novel rationale for the protein-protein interaction in cell physiology. Based on the first-exit time and the corresponding deterministic characterization of various genetic circuits, we show that the reversible binding dynamics may stabilize non-genetically inherited cell states, providing a practical strategy for designing robust epigenetic memory.

  2. Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression.

    Science.gov (United States)

    Shen, Shensi; Rodrigo, Guillermo; Prakash, Satya; Majer, Eszter; Landrain, Thomas E; Kirov, Boris; Daròs, José-Antonio; Jaramillo, Alfonso

    2015-05-26

    Organisms have different circuitries that allow converting signal molecule levels to changes in gene expression. An important challenge in synthetic biology involves the de novo design of RNA modules enabling dynamic signal processing in live cells. This requires a scalable methodology for sensing, transmission, and actuation, which could be assembled into larger signaling networks. Here, we present a biochemical strategy to design RNA-mediated signal transduction cascades able to sense small molecules and small RNAs. We design switchable functional RNA domains by using strand-displacement techniques. We experimentally characterize the molecular mechanism underlying our synthetic RNA signaling cascades, show the ability to regulate gene expression with transduced RNA signals, and describe the signal processing response of our systems to periodic forcing in single live cells. The engineered systems integrate RNA-RNA interaction with available ribozyme and aptamer elements, providing new ways to engineer arbitrary complex gene circuits.

  3. Analog circuit design designing dynamic circuit response

    CERN Document Server

    Feucht, Dennis

    2010-01-01

    This second volume, Designing Dynamic Circuit Response builds upon the first volume Designing Amplifier Circuits by extending coverage to include reactances and their time- and frequency-related behavioral consequences.

  4. Dynamical compensation in physiological circuits.

    Science.gov (United States)

    Karin, Omer; Swisa, Avital; Glaser, Benjamin; Dor, Yuval; Alon, Uri

    2016-11-08

    Biological systems can maintain constant steady-state output despite variation in biochemical parameters, a property known as exact adaptation. Exact adaptation is achieved using integral feedback, an engineering strategy that ensures that the output of a system robustly tracks its desired value. However, it is unclear how physiological circuits also keep their output dynamics precise-including the amplitude and response time to a changing input. Such robustness is crucial for endocrine and neuronal homeostatic circuits because they need to provide a precise dynamic response in the face of wide variation in the physiological parameters of their target tissues; how such circuits compensate their dynamics for unavoidable natural fluctuations in parameters is unknown. Here, we present a design principle that provides the desired robustness, which we call dynamical compensation (DC). We present a class of circuits that show DC by means of a nonlinear feedback loop in which the regulated variable controls the functional mass of the controlling endocrine or neuronal tissue. This mechanism applies to the control of blood glucose by insulin and explains several experimental observations on insulin resistance. We provide evidence that this mechanism may also explain compensation and organ size control in other physiological circuits.

  5. Chaotic memristive circuit: equivalent circuit realization and dynamical analysis

    Institute of Scientific and Technical Information of China (English)

    Bao Bo-Cheng; Xu Jian-Ping; Zhou Guo-Hua; Ma Zheng-Hua; Zou Ling

    2011-01-01

    In this paper,a practical equivalent circuit of an active flux-controlled memristor characterized by smooth piecewise-quadratic nonlinearity is designed and an experimental chaotic memristive circuit is implemented.The chaotic memristive circuit has an equilibrium set and its stability is dependent on the initial state of the memristor.The initial state-dependent and the circuit parameter-dependent dynamics of the chaotic memristive circuit are investigated via phase portraits,bifurcation diagrams and Lyapunov exponents.Both experimental and simulation results validate the proposed equivalent circuit realization of the active flux-controlled memristor.

  6. Digital and analog gene circuits for biotechnology.

    Science.gov (United States)

    Roquet, Nathaniel; Lu, Timothy K

    2014-05-01

    Biotechnology offers the promise of valuable chemical production via microbial processing of renewable and inexpensive substrates. Thus far, static metabolic engineering strategies have enabled this field to advance industrial applications. However, the industrial scaling of statically engineered microbes inevitably creates inefficiencies due to variable conditions present in large-scale microbial cultures. Synthetic gene circuits that dynamically sense and regulate different molecules can resolve this issue by enabling cells to continuously adapt to variable conditions. These circuits also have the potential to enable next-generation production programs capable of autonomous transitioning between steps in a bioprocess. Here, we review the design and application of two main classes of dynamic gene circuits, digital and analog, for biotechnology. Within the context of these classes, we also discuss the potential benefits of digital-analog interconversion, memory, and multi-signal integration. Though synthetic gene circuits have largely been applied for cellular computation to date, we envision that utilizing them in biotechnology will enhance the efficiency and scope of biochemical production with living cells.

  7. Spatiotemporal dynamics of distributed synthetic genetic circuits

    Science.gov (United States)

    Kanakov, Oleg; Laptyeva, Tetyana; Tsimring, Lev; Ivanchenko, Mikhail

    2016-04-01

    We propose and study models of two distributed synthetic gene circuits, toggle-switch and oscillator, each split between two cell strains and coupled via quorum-sensing signals. The distributed toggle switch relies on mutual repression of the two strains, and oscillator is comprised of two strains, one of which acts as an activator for another that in turn acts as a repressor. Distributed toggle switch can exhibit mobile fronts, switching the system from the weaker to the stronger spatially homogeneous state. The circuit can also act as a biosensor, with the switching front dynamics determined by the properties of an external signal. Distributed oscillator system displays another biosensor functionality: oscillations emerge once a small amount of one cell strain appears amid the other, present in abundance. Distribution of synthetic gene circuits among multiple strains allows one to reduce crosstalk among different parts of the overall system and also decrease the energetic burden of the synthetic circuit per cell, which may allow for enhanced functionality and viability of engineered cells.

  8. Tools and Principles for Microbial Gene Circuit Engineering.

    Science.gov (United States)

    Bradley, Robert W; Buck, Martin; Wang, Baojun

    2016-02-27

    Synthetic biologists aim to construct novel genetic circuits with useful applications through rational design and forward engineering. Given the complexity of signal processing that occurs in natural biological systems, engineered microbes have the potential to perform a wide range of desirable tasks that require sophisticated computation and control. Realising this goal will require accurate predictive design of complex synthetic gene circuits and accompanying large sets of quality modular and orthogonal genetic parts. Here we present a current overview of the versatile components and tools available for engineering gene circuits in microbes, including recently developed RNA-based tools that possess large dynamic ranges and can be easily programmed. We introduce design principles that enable robust and scalable circuit performance such as insulating a gene circuit against unwanted interactions with its context, and we describe efficient strategies for rapidly identifying and correcting causes of failure and fine-tuning circuit characteristics.

  9. Frequency domain analysis of noise in autoregulated gene circuits

    OpenAIRE

    Simpson, Michael L.; Cox, Chris D.; Sayler, Gary S.

    2003-01-01

    We describe a frequency domain technique for the analysis of intrinsic noise within negatively autoregulated gene circuits. This approach is based on the transfer function around the feedback loop (loop transmission) and the equivalent noise bandwidth of the system. The loop transmission, T, is shown to be a determining factor of the dynamics and the noise behavior of autoregulated gene circuits, and this T-based technique provides a simple and flexible method for the analysis of noise arisin...

  10. Frequency domain analysis of noise in autoregulated gene circuits

    Science.gov (United States)

    Simpson, Michael L.; Cox, Chris D.; Sayler, Gary S.

    2003-01-01

    We describe a frequency domain technique for the analysis of intrinsic noise within negatively autoregulated gene circuits. This approach is based on the transfer function around the feedback loop (loop transmission) and the equivalent noise bandwidth of the system. The loop transmission, T, is shown to be a determining factor of the dynamics and the noise behavior of autoregulated gene circuits, and this T-based technique provides a simple and flexible method for the analysis of noise arising from any source within the gene circuit. We show that negative feedback not only reduces the variance of the noise in the protein concentration, but also shifts this noise to higher frequencies where it may have a negligible effect on the noise behavior of following gene circuits within a cascade. This predicted effect is demonstrated through the exact stochastic simulation of a two-gene cascade. The analysis elucidates important aspects of gene circuit structure that control functionality, and may provide some insights into selective pressures leading to this structure. The resulting analytical relationships have a simple form, making them especially useful as synthetic gene circuit design equations. With the exception of the linearization of Hill kinetics, this technique is general and may be applied to the analysis or design of networks of higher complexity. This utility is demonstrated through the exact stochastic simulation of an autoregulated two-gene cascade operating near instability. PMID:12671069

  11. Photonic gene circuits by optically addressable siRNA-Au nanoantennas.

    Science.gov (United States)

    Lee, Somin Eunice; Sasaki, Darryl Y; Park, Younggeun; Xu, Ren; Brennan, James S; Bissell, Mina J; Lee, Luke P

    2012-09-25

    The precise perturbation of gene circuits and the direct observation of signaling pathways in living cells are essential for both fundamental biology and translational medicine. Current optogenetic technology offers a new paradigm of optical control for cells; however, this technology relies on permanent genomic modifications with light-responsive genes, thus limiting dynamic reconfiguration of gene circuits. Here, we report precise control of perturbation and reconfiguration of gene circuits in living cells by optically addressable siRNA-Au nanoantennas. The siRNA-Au nanoantennas fulfill dual functions as selectively addressable optical receivers and biomolecular emitters of small interfering RNA (siRNA). Using siRNA-Au nanoantennas as optical inputs to existing circuit connections, photonic gene circuits are constructed in living cells. We show that photonic gene circuits are modular, enabling subcircuits to be combined on-demand. Photonic gene circuits open new avenues for engineering functional gene circuits useful for fundamental bioscience, bioengineering, and medical applications.

  12. Lower Bounds for Tropical Circuits and Dynamic Programs

    OpenAIRE

    Jukna, Stasys

    2014-01-01

    Tropical circuits are circuits with Min and Plus, or Max and Plus operations as gates. Their importance stems from their intimate relation to dynamic programming algorithms. The power of tropical circuits lies somewhere between that of monotone boolean circuits and monotone arithmetic circuits. In this paper we present some lower bounds arguments for tropical circuits, and hence, for dynamic programs.

  13. Automatic design of digital synthetic gene circuits.

    Directory of Open Access Journals (Sweden)

    Mario A Marchisio

    2011-02-01

    Full Text Available De novo computational design of synthetic gene circuits that achieve well-defined target functions is a hard task. Existing, brute-force approaches run optimization algorithms on the structure and on the kinetic parameter values of the network. However, more direct rational methods for automatic circuit design are lacking. Focusing on digital synthetic gene circuits, we developed a methodology and a corresponding tool for in silico automatic design. For a given truth table that specifies a circuit's input-output relations, our algorithm generates and ranks several possible circuit schemes without the need for any optimization. Logic behavior is reproduced by the action of regulatory factors and chemicals on the promoters and on the ribosome binding sites of biological Boolean gates. Simulations of circuits with up to four inputs show a faithful and unequivocal truth table representation, even under parametric perturbations and stochastic noise. A comparison with already implemented circuits, in addition, reveals the potential for simpler designs with the same function. Therefore, we expect the method to help both in devising new circuits and in simplifying existing solutions.

  14. Automatic design of digital synthetic gene circuits.

    Science.gov (United States)

    Marchisio, Mario A; Stelling, Jörg

    2011-02-01

    De novo computational design of synthetic gene circuits that achieve well-defined target functions is a hard task. Existing, brute-force approaches run optimization algorithms on the structure and on the kinetic parameter values of the network. However, more direct rational methods for automatic circuit design are lacking. Focusing on digital synthetic gene circuits, we developed a methodology and a corresponding tool for in silico automatic design. For a given truth table that specifies a circuit's input-output relations, our algorithm generates and ranks several possible circuit schemes without the need for any optimization. Logic behavior is reproduced by the action of regulatory factors and chemicals on the promoters and on the ribosome binding sites of biological Boolean gates. Simulations of circuits with up to four inputs show a faithful and unequivocal truth table representation, even under parametric perturbations and stochastic noise. A comparison with already implemented circuits, in addition, reveals the potential for simpler designs with the same function. Therefore, we expect the method to help both in devising new circuits and in simplifying existing solutions.

  15. Dynamics and plasticity of spinal locomotor circuits.

    Science.gov (United States)

    El Manira, Abdeljabbar

    2014-12-01

    Spinal circuits generate coordinated locomotor movements. These hardwired circuits are supplemented with neuromodulation that provide the necessary flexibility for animals to move smoothly through their environment. This review will highlight some recent insights gained in understanding the functional dynamics and plasticity of the locomotor circuits. First the mechanisms governing the modulation of the speed of locomotion will be discussed. Second, advantages of the modular organization of the locomotor networks with multiple circuits engaged in a task-dependent manner will be examined. Finally, the neuromodulation and the resulting plasticity of the locomotor circuits will be summarized with an emphasis on endocannabinoids and nitric oxide. The intention is to extract general principles of organization and discuss some onto-genetic and phylogenetic divergences.

  16. Dynamics of pi-junction interferometer circuits

    DEFF Research Database (Denmark)

    Kornkev, V.K.; Mozhaev, P.B.; Borisenko, I.V.;

    2002-01-01

    The pi-junction superconducting circuit dynamics was studied by means of numerical simulation technique. Parallel arrays consisting of Josephson junctions of both 0- and pi-type were studied as a model of high-T-c grain-boundary Josephson junction. The array dynamics and the critical current...

  17. Dynamics of pi-junction interferometer circuits

    DEFF Research Database (Denmark)

    Kornkev, V.K.; Mozhaev, P.B.; Borisenko, I.V.

    2002-01-01

    The pi-junction superconducting circuit dynamics was studied by means of numerical simulation technique. Parallel arrays consisting of Josephson junctions of both 0- and pi-type were studied as a model of high-T-c grain-boundary Josephson junction. The array dynamics and the critical current...

  18. Effects of cell cycle noise on excitable gene circuits

    CERN Document Server

    Veliz-Cuba, Alan; Bennett, Matthew R; Josić, Krešimir; Ott, William

    2016-01-01

    We assess the impact of cell cycle noise on gene circuit dynamics. For bistable genetic switches and excitable circuits, we find that transitions between metastable states most likely occur just after cell division and that this concentration effect intensifies in the presence of transcriptional delay. We explain this concentration effect with a 3-states stochastic model. For genetic oscillators, we quantify the temporal correlations between daughter cells induced by cell division. Temporal correlations must be captured properly in order to accurately quantify noise sources within gene networks.

  19. Nonlinear dynamics based digital logic and circuits.

    Science.gov (United States)

    Kia, Behnam; Lindner, John F; Ditto, William L

    2015-01-01

    We discuss the role and importance of dynamics in the brain and biological neural networks and argue that dynamics is one of the main missing elements in conventional Boolean logic and circuits. We summarize a simple dynamics based computing method, and categorize different techniques that we have introduced to realize logic, functionality, and programmability. We discuss the role and importance of coupled dynamics in networks of biological excitable cells, and then review our simple coupled dynamics based method for computing. In this paper, for the first time, we show how dynamics can be used and programmed to implement computation in any given base, including but not limited to base two.

  20. Dynamical systems, attractors, and neural circuits.

    Science.gov (United States)

    Miller, Paul

    2016-01-01

    Biology is the study of dynamical systems. Yet most of us working in biology have limited pedagogical training in the theory of dynamical systems, an unfortunate historical fact that can be remedied for future generations of life scientists. In my particular field of systems neuroscience, neural circuits are rife with nonlinearities at all levels of description, rendering simple methodologies and our own intuition unreliable. Therefore, our ideas are likely to be wrong unless informed by good models. These models should be based on the mathematical theories of dynamical systems since functioning neurons are dynamic-they change their membrane potential and firing rates with time. Thus, selecting the appropriate type of dynamical system upon which to base a model is an important first step in the modeling process. This step all too easily goes awry, in part because there are many frameworks to choose from, in part because the sparsely sampled data can be consistent with a variety of dynamical processes, and in part because each modeler has a preferred modeling approach that is difficult to move away from. This brief review summarizes some of the main dynamical paradigms that can arise in neural circuits, with comments on what they can achieve computationally and what signatures might reveal their presence within empirical data. I provide examples of different dynamical systems using simple circuits of two or three cells, emphasizing that any one connectivity pattern is compatible with multiple, diverse functions.

  1. Rett syndrome: genes, synapses, circuits and therapeutics

    Directory of Open Access Journals (Sweden)

    Abhishek eBanerjee

    2012-05-01

    Full Text Available Development of the nervous system proceeds through a set of complex checkpoints which arise from a combination of sequential gene expression and early neural activity sculpted by the environment. Genetic and environmental insults lead to neurodevelopmental disorders which encompass a large group of diseases that result from anatomical and physiological abnormalities during maturation and development of brain circuits. Rett syndrome (RTT is a postnatal neurological disorder of genetic origin, caused by mutations in the X-linked gene MECP2. It features neuropsychiatric abnormalities like motor dysfunctions and mild to severe cognitive impairment. This review discusses several key questions and attempts to evaluate recently developed animal models, cell-type specific function of MeCP2, defects in neural circuit plasticity and possible therapeutic strategies. Finally, we also discuss how genes, proteins and overlapping signaling pathways affect the molecular etiology of apparently unrelated neuropsychiatric disorders, an understanding of which can offer novel therapeutic strategies.

  2. Dynamic Circuit Model for Spintronic Devices

    KAUST Repository

    Alawein, Meshal

    2017-01-09

    In this work we propose a finite-difference scheme based circuit model of a general spintronic device and benchmark it with other models proposed for spintronic switching devices. Our model is based on the four-component spin circuit theory and utilizes the widely used coupled stochastic magnetization dynamics/spin transport framework. In addition to the steady-state analysis, this work offers a transient analysis of carrier transport. By discretizing the temporal and spatial derivatives to generate a linear system of equations, we derive new and simple finite-difference conductance matrices that can, to the first order, capture both static and dynamic behaviors of a spintronic device. We also discuss an extension of the spin modified nodal analysis (SMNA) for time-dependent situations based on the proposed scheme.

  3. Low Power, Reduced Dynamic Voltage Swing Domino Logic Circuits

    OpenAIRE

    Salendra.Govindarajulu; Dr.T.Jayachandra Prasad; Rangappa, P

    2010-01-01

    Dynamic domino logic circuits are widely used in modern digital VLSI circuits. These dynamic circuits are often favoured in high performance designs because of the speed advantage offered over static CMOS logic circuits. The main drawbacks of dynamic logic are a lack of design automation, a decreased tolerance to noise and increased power dissipation. In this work, new reduced – swing domino logic techniques which provide significant low power dissipation as compared to traditional domino cir...

  4. Optical Recording of Neuronal Circuit Dynamics

    OpenAIRE

    Wolf, Alexander

    2007-01-01

    This work deals with the optical recording of cerebellar circuit dynamics from acute brain slices of the cerebellar surface. This preparation preserves the functional connectivity of the cerebellar cortex. It was used to investigate the function of Kv3 potassium channels in the cerebellar granule cell axon. Double knockout mice lacking both Kv3.1 and Kv3.3 potassium channels display severe motor deficits, while mice lacking only Kv3.1 or Kv3.3 do not. Since granule cells express both Kv3.1 an...

  5. Nonlinear electronic circuit with neuron like bursting and spiking dynamics.

    Science.gov (United States)

    Savino, Guillermo V; Formigli, Carlos M

    2009-07-01

    It is difficult to design electronic nonlinear devices capable of reproducing complex oscillations because of the lack of general constructive rules, and because of stability problems related to the dynamical robustness of the circuits. This is particularly true for current analog electronic circuits that implement mathematical models of bursting and spiking neurons. Here we describe a novel, four-dimensional and dynamically robust nonlinear analog electronic circuit that is intrinsic excitable, and that displays frequency adaptation bursting and spiking oscillations. Despite differences from the classical Hodgkin-Huxley (HH) neuron model, its bifurcation sequences and dynamical properties are preserved, validating the circuit as a neuron model. The circuit's performance is based on a nonlinear interaction of fast-slow circuit blocks that can be clearly dissected, elucidating burst's starting, sustaining and stopping mechanisms, which may also operate in real neurons. Our analog circuit unit is easily linked and may be useful in building networks that perform in real-time.

  6. Constraint and contingency in multifunctional gene regulatory circuits.

    Science.gov (United States)

    Payne, Joshua L; Wagner, Andreas

    2013-01-01

    Gene regulatory circuits drive the development, physiology, and behavior of organisms from bacteria to humans. The phenotypes or functions of such circuits are embodied in the gene expression patterns they form. Regulatory circuits are typically multifunctional, forming distinct gene expression patterns in different embryonic stages, tissues, or physiological states. Any one circuit with a single function can be realized by many different regulatory genotypes. Multifunctionality presumably constrains this number, but we do not know to what extent. We here exhaustively characterize a genotype space harboring millions of model regulatory circuits and all their possible functions. As a circuit's number of functions increases, the number of genotypes with a given number of functions decreases exponentially but can remain very large for a modest number of functions. However, the sets of circuits that can form any one set of functions becomes increasingly fragmented. As a result, historical contingency becomes widespread in circuits with many functions. Whether a circuit can acquire an additional function in the course of its evolution becomes increasingly dependent on the function it already has. Circuits with many functions also become increasingly brittle and sensitive to mutation. These observations are generic properties of a broad class of circuits and independent of any one circuit genotype or phenotype.

  7. Rapid, modular and reliable construction of complex mammalian gene circuits.

    Science.gov (United States)

    Guye, Patrick; Li, Yinqing; Wroblewska, Liliana; Duportet, Xavier; Weiss, Ron

    2013-09-01

    We developed a framework for quick and reliable construction of complex gene circuits for genetically engineering mammalian cells. Our hierarchical framework is based on a novel nucleotide addressing system for defining the position of each part in an overall circuit. With this framework, we demonstrate construction of synthetic gene circuits of up to 64 kb in size comprising 11 transcription units and 33 basic parts. We show robust gene expression control of multiple transcription units by small molecule inducers in human cells with transient transfection and stable chromosomal integration of these circuits. This framework enables development of complex gene circuits for engineering mammalian cells with unprecedented speed, reliability and scalability and should have broad applicability in a variety of areas including mammalian cell fermentation, cell fate reprogramming and cell-based assays.

  8. Dynamics of Hamiltonian Systems and Memristor Circuits

    Science.gov (United States)

    Itoh, Makoto; Chua, Leon

    In this paper, we show that any n-dimensional autonomous systems can be regarded as subsystems of 2n-dimensional Hamiltonian systems. One of the two subsystems is identical to the n-dimensional autonomous system, which is called the driving system. Another subsystem, called the response system, can exhibit interesting behaviors in the neighborhood of infinity. That is, the trajectories approach infinity with complicated nonperiodic (chaotic-like) behaviors, or periodic-like behavior. In order to show the above results, we project the trajectories of the Hamiltonian systems onto n-dimensional spheres, or n-dimensional balls by using the well-known central projection transformation. Another interesting behavior is that the transient regime of the subsystems can exhibit Chua corsage knots. We next show that generic memristors can be used to realize the above Hamiltonian systems. Finally, we show that the internal state of two-element memristor circuits can have the same dynamics as n-dimensional autonomous systems.

  9. No tradeoff between versatility and robustness in gene circuit motifs

    Science.gov (United States)

    Payne, Joshua L.

    2016-05-01

    Circuit motifs are small directed subgraphs that appear in real-world networks significantly more often than in randomized networks. In the Boolean model of gene circuits, most motifs are realized by multiple circuit genotypes. Each of a motif's constituent circuit genotypes may have one or more functions, which are embodied in the expression patterns the circuit forms in response to specific initial conditions. Recent enumeration of a space of nearly 17 million three-gene circuit genotypes revealed that all circuit motifs have more than one function, with the number of functions per motif ranging from 12 to nearly 30,000. This indicates that some motifs are more functionally versatile than others. However, the individual circuit genotypes that constitute each motif are less robust to mutation if they have many functions, hinting that functionally versatile motifs may be less robust to mutation than motifs with few functions. Here, I explore the relationship between versatility and robustness in circuit motifs, demonstrating that functionally versatile motifs are robust to mutation despite the inherent tradeoff between versatility and robustness at the level of an individual circuit genotype.

  10. Engineering Synthetic Gene Circuits in Living Cells with CRISPR Technology.

    Science.gov (United States)

    Jusiak, Barbara; Cleto, Sara; Perez-Piñera, Pablo; Lu, Timothy K

    2016-07-01

    One of the goals of synthetic biology is to build regulatory circuits that control cell behavior, for both basic research purposes and biomedical applications. The ability to build transcriptional regulatory devices depends on the availability of programmable, sequence-specific, and effective synthetic transcription factors (TFs). The prokaryotic clustered regularly interspaced short palindromic repeat (CRISPR) system, recently harnessed for transcriptional regulation in various heterologous host cells, offers unprecedented ease in designing synthetic TFs. We review how CRISPR can be used to build synthetic gene circuits and discuss recent advances in CRISPR-mediated gene regulation that offer the potential to build increasingly complex, programmable, and efficient gene circuits in the future.

  11. Dynamic programming in in uence diagrams with decision circuits

    CERN Document Server

    Shachter, Ross D

    2012-01-01

    Decision circuits perform efficient evaluation of influence diagrams, building on the ad- vances in arithmetic circuits for belief net- work inference [Darwiche, 2003; Bhattachar- jya and Shachter, 2007]. We show how even more compact decision circuits can be con- structed for dynamic programming in influ- ence diagrams with separable value functions and conditionally independent subproblems. Once a decision circuit has been constructed based on the diagram's "global" graphical structure, it can be compiled to exploit "lo- cal" structure for efficient evaluation and sen- sitivity analysis.

  12. Dynamical Systems in Circuit Designer's Eyes

    Energy Technology Data Exchange (ETDEWEB)

    Odyniec, M.

    2011-05-09

    Examples of nonlinear circuit design are given. Focus of the design process is on theory and engineering methods (as opposed to numerical analysis). Modeling is related to measurements It is seen that the phase plane is still very useful with proper models Harmonic balance/describing function offers powerful insight (via the combination of simulation with circuit and ODE theory). Measurement and simulation capabilities increased, especially harmonics measurements (since sinusoids are easy to generate)

  13. Logarithmic circuit with wide dynamic range

    Science.gov (United States)

    Wiley, P. H.; Manus, E. A. (Inventor)

    1978-01-01

    A circuit deriving an output voltage that is proportional to the logarithm of a dc input voltage susceptible to wide variations in amplitude includes a constant current source which forward biases a diode so that the diode operates in the exponential portion of its voltage versus current characteristic, above its saturation current. The constant current source includes first and second, cascaded feedback, dc operational amplifiers connected in negative feedback circuit. An input terminal of the first amplifier is responsive to the input voltage. A circuit shunting the first amplifier output terminal includes a resistor in series with the diode. The voltage across the resistor is sensed at the input of the second dc operational feedback amplifier. The current flowing through the resistor is proportional to the input voltage over the wide range of variations in amplitude of the input voltage.

  14. A systematic molecular circuit design method for gene networks under biochemical time delays and molecular noises

    Directory of Open Access Journals (Sweden)

    Chang Yu-Te

    2008-11-01

    Full Text Available Abstract Background Gene networks in nanoscale are of nonlinear stochastic process. Time delays are common and substantial in these biochemical processes due to gene transcription, translation, posttranslation protein modification and diffusion. Molecular noises in gene networks come from intrinsic fluctuations, transmitted noise from upstream genes, and the global noise affecting all genes. Knowledge of molecular noise filtering and biochemical process delay compensation in gene networks is crucial to understand the signal processing in gene networks and the design of noise-tolerant and delay-robust gene circuits for synthetic biology. Results A nonlinear stochastic dynamic model with multiple time delays is proposed for describing a gene network under process delays, intrinsic molecular fluctuations, and extrinsic molecular noises. Then, the stochastic biochemical processing scheme of gene regulatory networks for attenuating these molecular noises and compensating process delays is investigated from the nonlinear signal processing perspective. In order to improve the robust stability for delay toleration and noise filtering, a robust gene circuit for nonlinear stochastic time-delay gene networks is engineered based on the nonlinear robust H∞ stochastic filtering scheme. Further, in order to avoid solving these complicated noise-tolerant and delay-robust design problems, based on Takagi-Sugeno (T-S fuzzy time-delay model and linear matrix inequalities (LMIs technique, a systematic gene circuit design method is proposed to simplify the design procedure. Conclusion The proposed gene circuit design method has much potential for application to systems biology, synthetic biology and drug design when a gene regulatory network has to be designed for improving its robust stability and filtering ability of disease-perturbed gene network or when a synthetic gene network needs to perform robustly under process delays and molecular noises.

  15. Analog VLSI Circuits for Short-Term Dynamic Synapses

    Directory of Open Access Journals (Sweden)

    Shih-Chii Liu

    2003-06-01

    Full Text Available Short-term dynamical synapses increase the computational power of neuronal networks. These synapses act as additional filters to the inputs of a neuron before the subsequent integration of these signals at its cell body. In this work, we describe a model of depressing and facilitating synapses derived from a hardware circuit implementation. This model is equivalent to theoretical models of short-term synaptic dynamics in network simulations. These circuits have been added to a network of leaky integrate-and-fire neurons. A cortical model of direction-selectivity that uses short-term dynamic synapses has been implemented with this network.

  16. High-speed dynamic domino circuit implemented with gaas mesfets

    Science.gov (United States)

    Yang, Long (Inventor); Long, Stephen I. (Inventor)

    1990-01-01

    A dynamic logic circuit (AND or OR) utilizes one depletion-mode metal-semiconductor FET for precharging an internal node A, and a plurality of the same type of FETs in series, or a FET in parallel with one or more of the series connected FETs for implementing the logic function. A pair of FETs are connected to provide an output inverter with two series diodes for level shift. A coupling capacitor may be employed with a further FET to provide level shifting required between the inverter and the logic circuit output terminal. These circuits may be cascaded to form a domino chain.

  17. Circuit Modeling of a MEMS Varactor Including Dielectric Charging Dynamics

    Science.gov (United States)

    Giounanlis, P.; Andrade-Miceli, D.; Gorreta, S.; Pons-Nin, J.; Dominguez-Pumar, M.; Blokhina, E.

    2016-10-01

    Electrical models for MEMS varactors including the effect of dielectric charging dynamics are not available in commercial circuit simulators. In this paper a circuit model using lumped ideal elements available in the Cadence libraries and a basic Verilog-A model, has been implemented. The model has been used to simulate the dielectric charging in function of time and its effects over the MEMS capacitance value.

  18. Neural circuits as computational dynamical systems.

    Science.gov (United States)

    Sussillo, David

    2014-04-01

    Many recent studies of neurons recorded from cortex reveal complex temporal dynamics. How such dynamics embody the computations that ultimately lead to behavior remains a mystery. Approaching this issue requires developing plausible hypotheses couched in terms of neural dynamics. A tool ideally suited to aid in this question is the recurrent neural network (RNN). RNNs straddle the fields of nonlinear dynamical systems and machine learning and have recently seen great advances in both theory and application. I summarize recent theoretical and technological advances and highlight an example of how RNNs helped to explain perplexing high-dimensional neurophysiological data in the prefrontal cortex.

  19. A framework for scalable parameter estimation of gene circuit models using structural information

    KAUST Repository

    Kuwahara, Hiroyuki

    2013-06-21

    Motivation: Systematic and scalable parameter estimation is a key to construct complex gene regulatory models and to ultimately facilitate an integrative systems biology approach to quantitatively understand the molecular mechanisms underpinning gene regulation. Results: Here, we report a novel framework for efficient and scalable parameter estimation that focuses specifically on modeling of gene circuits. Exploiting the structure commonly found in gene circuit models, this framework decomposes a system of coupled rate equations into individual ones and efficiently integrates them separately to reconstruct the mean time evolution of the gene products. The accuracy of the parameter estimates is refined by iteratively increasing the accuracy of numerical integration using the model structure. As a case study, we applied our framework to four gene circuit models with complex dynamics based on three synthetic datasets and one time series microarray data set. We compared our framework to three state-of-the-art parameter estimation methods and found that our approach consistently generated higher quality parameter solutions efficiently. Although many general-purpose parameter estimation methods have been applied for modeling of gene circuits, our results suggest that the use of more tailored approaches to use domain-specific information may be a key to reverse engineering of complex biological systems. The Author 2013.

  20. Path Tracking of dynamics of a Chaotic Memristor Circuit

    Directory of Open Access Journals (Sweden)

    H. Vazquez-Leal

    2014-05-01

    Full Text Available Since its recent invention, the Memristor has proven to be a revolutionary device due to the versatility of its applications. Among these, the study of chaotic circuits using Memristors is a fertile area to be explored. However, despite several ways to track the chaotic paths for memristive circuits have been previously proposed, all of these provide merely numeric or qualitatively solutions. As it could be necessary for some applications to have all the possible information about their dynamics, a new methodology to path tracking the chaotic trajectories for memristive circuits using the Multistage Homotopy Perturbation Method is proposed. This methodology provides a straightforward semi-analytic expression to obtain the chaotic path in an iterative way, providing both, the numeric and qualitative behaviour of the circuit.

  1. Hox genes: choreographers in neural development, architects of circuit organization.

    Science.gov (United States)

    Philippidou, Polyxeni; Dasen, Jeremy S

    2013-10-02

    The neural circuits governing vital behaviors, such as respiration and locomotion, are comprised of discrete neuronal populations residing within the brainstem and spinal cord. Work over the past decade has provided a fairly comprehensive understanding of the developmental pathways that determine the identity of major neuronal classes within the neural tube. However, the steps through which neurons acquire the subtype diversities necessary for their incorporation into a particular circuit are still poorly defined. Studies on the specification of motor neurons indicate that the large family of Hox transcription factors has a key role in generating the subtypes required for selective muscle innervation. There is also emerging evidence that Hox genes function in multiple neuronal classes to shape synaptic specificity during development, suggesting a broader role in circuit assembly. This Review highlights the functions and mechanisms of Hox gene networks and their multifaceted roles during neuronal specification and connectivity.

  2. Dynamical Casimir effect in Circuit QED for Nonuniform Trajectories

    CERN Document Server

    Corona-Ugalde, Paulina; Wilson, C M; Mann, Robert B

    2015-01-01

    We propose a generalization of the superconducting circuit simulation of the dynamical Casimir effect where we consider relativistically moving boundary conditions following different trajectories. We study the feasibility of the setup used in the past to simulate the dynamical Casimir effect to reproduce richer relativistic trajectories differing from purely sinusoidal ones. We show how different relativistic oscillatory trajectories of the boundaries of the same period and similar shape produce a rather different spectrum of particles characteristic of their respective motions.

  3. Visual experience modulates spatio-temporal dynamics of circuit activation

    Directory of Open Access Journals (Sweden)

    Lang eWang

    2011-06-01

    Full Text Available Persistent reduction in sensory drive in early development results in multiple plastic changes of different cortical synapses. How these experience-dependent modifications affect the spatio-temporal dynamics of signal propagation in neocortical circuits is poorly understood. Here we demonstrate that brief visual deprivation significantly affects the propagation of electrical signals in the primary visual cortex. The spatio-temporal spread of circuit activation upon direct stimulation of its input layer (Layer 4 is reduced, as is the activation of Layer 2/3 – the main recipient of the output from Layer 4. Our data suggest that the decrease in spatio-temporal activation of L2/3 depends on reduced L4 output, and is not intrinsically generated within L2/3. The data shown here suggest that changes in the synaptic components of the visual cortical circuit result not only in alteration of local integration of excitatory and inhibitory inputs, but also in a significant decrease in overall circuit activation. Furthermore, our data indicate a differential effect of visual deprivation on L4 and L2/3, suggesting that while feedforward activation of L2/3 is reduced, its activation by long range, within layer inputs is unaltered. Thus, brief visual deprivation induces experience-dependent circuit re-organization by modulating not only circuit excitability, but also the spatio-temporal patterns of cortical activation within and between layers.

  4. Quantum Simulation of the Ultrastrong Coupling Dynamics in Circuit QED

    CERN Document Server

    Ballester, D; García-Ripoll, J J; Deppe, F; Solano, E

    2011-01-01

    We propose a method to get experimental access to the physics of the ultrastrong (USC) and deep strong (DSC) coupling regimes of light-matter interaction through the quantum simulation of their dynamics in standard circuit QED. The method makes use of a two-tone driving scheme, using state-of-the-art circuit-QED technology, and can be easily extended to general quantum optical cavity-QED setups. We provide examples of USC/DSC quantum effects that would be otherwise unaccessible.

  5. Reversible circuit synthesis by genetic programming using dynamic gate libraries

    Science.gov (United States)

    Abubakar, Mustapha Y.; Jung, Low Tang; Zakaria, Nordin; Younes, Ahmed; Abdel-Aty, Abdel-Haleem

    2017-06-01

    We have defined a new method for automatic construction of reversible logic circuits by using the genetic programming approach. The choice of the gate library is 100% dynamic. The algorithm is capable of accepting all possible combinations of the following gate types: NOT TOFFOLI, NOT PERES, NOT CNOT TOFFOLI, NOT CNOT SWAP FREDKIN, NOT CNOT TOFFOLI SWAP FREDKIN, NOT CNOT PERES, NOT CNOT SWAP FREDKIN PERES, NOT CNOT TOFFOLI PERES and NOT CNOT TOFFOLI SWAP FREDKIN PERES. Our method produced near optimum circuits in some cases when a particular subset of gate types was used in the library. Meanwhile, in some cases, optimal circuits were produced due to the heuristic nature of the algorithm. We compared the outcomes of our method with several existing synthesis methods, and it was shown that our algorithm performed relatively well compared to the previous synthesis methods in terms of the output efficiency of the algorithm and execution time as well.

  6. Engineering robust and tunable spatial structures with synthetic gene circuits.

    Science.gov (United States)

    Kong, Wentao; Blanchard, Andrew E; Liao, Chen; Lu, Ting

    2017-01-25

    Controllable spatial patterning is a major goal for the engineering of biological systems. Recently, synthetic gene circuits have become promising tools to achieve the goal; however, they need to possess both functional robustness and tunability in order to facilitate future applications. Here we show that, by harnessing the dual signaling and antibiotic features of nisin, simple synthetic circuits can direct Lactococcus lactis populations to form programmed spatial band-pass structures that do not require fine-tuning and are robust against environmental and cellular context perturbations. Although robust, the patterns are highly tunable, with their band widths specified by the external nisin gradient and cellular nisin immunity. Additionally, the circuits can direct cells to consistently generate designed patterns, even when the gradient is driven by structured nisin-producing bacteria and the patterning cells are composed of multiple species. A mathematical model successfully reproduces all of the observed patterns. Furthermore, the circuits allow us to establish predictable structures of synthetic communities and controllable arrays of cellular stripes and spots in space. This study offers new synthetic biology tools to program spatial structures. It also demonstrates that a deep mining of natural functionalities of living systems is a valuable route to build circuit robustness and tunability.

  7. Advances in genetic circuit design: novel biochemistries, deep part mining, and precision gene expression.

    Science.gov (United States)

    Nielsen, Alec A K; Segall-Shapiro, Thomas H; Voigt, Christopher A

    2013-12-01

    Cells use regulatory networks to perform computational operations to respond to their environment. Reliably manipulating such networks would be valuable for many applications in biotechnology; for example, in having genes turn on only under a defined set of conditions or implementing dynamic or temporal control of expression. Still, building such synthetic regulatory circuits remains one of the most difficult challenges in genetic engineering and as a result they have not found widespread application. Here, we review recent advances that address the key challenges in the forward design of genetic circuits. First, we look at new design concepts, including the construction of layered digital and analog circuits, and new approaches to control circuit response functions. Second, we review recent work to apply part mining and computational design to expand the number of regulators that can be used together within one cell. Finally, we describe new approaches to obtain precise gene expression and to reduce context dependence that will accelerate circuit design by more reliably balancing regulators while reducing toxicity. Copyright © 2013. Published by Elsevier Ltd.

  8. Ruggedizing Printed Circuit Boards Using a Wideband Dynamic Absorber

    Directory of Open Access Journals (Sweden)

    V.C. Ho

    2003-01-01

    Full Text Available The existing approaches to ruggedizing inherently fragile and sensitive critical components of electronic equipment such as printed circuit boards (PCB for use in hostile industrial and military environment are either insufficient or expensive. This paper addresses a novel approach towards ruggedizing commercial-off-the-shelf PCBs using a miniature wideband dynamic absorber. The optimisation technique used relies on the experimentally measured vibration spectra and complex receptance of the original PCB.

  9. Synthetic multicellular oscillatory systems: controlling protein dynamics with genetic circuits

    Energy Technology Data Exchange (ETDEWEB)

    Koseska, Aneta [Interdisciplinary Center for Dynamics of Complex Systems, University of Potsdam, D-14469 Potsdam (Germany); Volkov, Evgenii [Department of Theoretical Physics, Lebedev Physical Institute, Leninskii 53, Moscow (Russian Federation); Kurths, Juergen, E-mail: akoseska@uni-potsdam.de [Institute of Physics, Humboldt University Berlin, D-10099 Berlin (Germany)

    2011-10-15

    Synthetic biology is a relatively new research discipline that combines standard biology approaches with the constructive nature of engineering. Thus, recent efforts in the field of synthetic biology have given a perspective to consider cells as 'programmable matter'. Here, we address the possibility of using synthetic circuits to control protein dynamics. In particular, we show how intercellular communication and stochasticity can be used to manipulate the dynamical behavior of a population of coupled synthetic units and, in this manner, finely tune the expression of specific proteins of interest, e.g. in large bioreactors.

  10. Modular construction of mammalian gene circuits using TALE transcriptional repressors.

    Science.gov (United States)

    Li, Yinqing; Jiang, Yun; Chen, He; Liao, Weixi; Li, Zhihua; Weiss, Ron; Xie, Zhen

    2015-03-01

    An important goal of synthetic biology is the rational design and predictable implementation of synthetic gene circuits using standardized and interchangeable parts. However, engineering of complex circuits in mammalian cells is currently limited by the availability of well-characterized and orthogonal transcriptional repressors. Here, we introduce a library of 26 reversible transcription activator-like effector repressors (TALERs) that bind newly designed hybrid promoters and exert transcriptional repression through steric hindrance of key transcriptional initiation elements. We demonstrate that using the input-output transfer curves of our TALERs enables accurate prediction of the behavior of modularly assembled TALER cascade and switch circuits. We also show that TALER switches using feedback regulation exhibit improved accuracy for microRNA-based HeLa cancer cell classification versus HEK293 cells. Our TALER library is a valuable toolkit for modular engineering of synthetic circuits, enabling programmable manipulation of mammalian cells and helping elucidate design principles of coupled transcriptional and microRNA-mediated post-transcriptional regulation.

  11. Experimental mastering of nonlinear dynamics in circuits by sporadic pulses

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz, P. [Instituto de Fisica de Cantabria IFCA (CSIC-UC), Santander (Spain); Gutierrez, J.M. [Department of Applied Mathematics and Computer Science, University of Cantabria, 39005 Santander (Spain)], E-mail: gutierjm@unican.es; Gueemez, J. [Department of Applied Physics, Universidad de Cantabria (Spain)

    2008-05-15

    We present some experimental evidence of mastering chaos (control and anticontrol) in nonlinear circuits using a simple impulsive method which does not require any knowledge about the system's dynamics. The method works by introducing instantaneous pulses in some system variables-in this paper the pulses are applied to a capacitor voltage-and, hence, is an additional plug-in that does not modify the system itself. When varying the mastering parameters (amplitude and frequency of pulses) we obtain a bifurcation structure similar to the one obtained when varying some system's parameters. Therefore, this device allows us investigating the dynamics of a given circuit providing us with a versatile component for performing both control or anticontrol of chaos. In particular, we show how a double-scroll chaotic system is stabilized in period three, single-scroll, period-4, period-2, period-1, fixed point, following an inverse bifurcation route as a function of the pulses amplitude (chaos control). It is also shown how a periodic Chua's circuit is driven to chaotic behavior (chaos anticontrol)

  12. Decreasing the stochasticity of mammalian gene expression by a synthetic gene circuit

    Science.gov (United States)

    Nevozhay, Dmitry; Zal, Tomasz; Balazsi, Gabor

    2012-02-01

    Gene therapy and functional genetic studies usually require precisely controlled and uniform gene expression in a population of cells for reliable level of protein production. Due to this requirement, stochastic gene expression is perceived as undesirable in these fields and ideally has to be minimized. The number of approaches for decreasing gene expression stochasticity in mammalian cells is limited. This creates an unmet need to develop new gene expression systems for this purpose. Based on earlier synthetic constructs in yeast, we developed and assessed a negative feedback-based mammalian gene circuit, with uniform and low level of stochasticity in gene expression at different levels of induction. In addition, this new synthetic construct enables highly precise gene expression control in mammalian cells, due to the linear dependence of gene expression on the inducer concentration applied to the system. This mammalian gene expression circuit has potential applicability for the development of new treatment modalities in gene therapy and research tools in functional genetics. In addition, this work creates a roadmap for moving synthetic gene circuits from microbes into mammalian cells.

  13. Genome engineering using a synthetic gene circuit in Bacillus subtilis.

    Science.gov (United States)

    Jeong, Da-Eun; Park, Seung-Hwan; Pan, Jae-Gu; Kim, Eui-Joong; Choi, Soo-Keun

    2015-03-31

    Genome engineering without leaving foreign DNA behind requires an efficient counter-selectable marker system. Here, we developed a genome engineering method in Bacillus subtilis using a synthetic gene circuit as a counter-selectable marker system. The system contained two repressible promoters (B. subtilis xylA (Pxyl) and spac (Pspac)) and two repressor genes (lacI and xylR). Pxyl-lacI was integrated into the B. subtilis genome with a target gene containing a desired mutation. The xylR and Pspac-chloramphenicol resistant genes (cat) were located on a helper plasmid. In the presence of xylose, repression of XylR by xylose induced LacI expression, the LacIs repressed the Pspac promoter and the cells become chloramphenicol sensitive. Thus, to survive in the presence of chloramphenicol, the cell must delete Pxyl-lacI by recombination between the wild-type and mutated target genes. The recombination leads to mutation of the target gene. The remaining helper plasmid was removed easily under the chloramphenicol absent condition. In this study, we showed base insertion, deletion and point mutation of the B. subtilis genome without leaving any foreign DNA behind. Additionally, we successfully deleted a 2-kb gene (amyE) and a 38-kb operon (ppsABCDE). This method will be useful to construct designer Bacillus strains for various industrial applications.

  14. Time- and Site-Resolved Dynamics in a Topological Circuit

    Directory of Open Access Journals (Sweden)

    Jia Ningyuan

    2015-06-01

    Full Text Available From studies of exotic quantum many-body phenomena to applications in spintronics and quantum information processing, topological materials are poised to revolutionize the condensed-matter frontier and the landscape of modern materials science. Accordingly, there is a broad effort to realize topologically nontrivial electronic and photonic materials for fundamental science as well as practical applications. In this work, we demonstrate the first simultaneous site- and time-resolved measurements of a time-reversal-invariant topological band structure, which we realize in a radio-frequency photonic circuit. We control band-structure topology via local permutation of a traveling-wave capacitor-inductor network, increasing robustness by going beyond the tight-binding limit. We observe a gapped density of states consistent with a modified Hofstadter spectrum at a flux per plaquette of ϕ=π/2. In situ probes of the band gaps reveal spatially localized bulk states and delocalized edge states. Time-resolved measurements reveal dynamical separation of localized edge excitations into spin-polarized currents. The radio-frequency circuit paradigm is naturally compatible with nonlocal coupling schemes, allowing us to implement a Möbius strip topology inaccessible in conventional systems. This room-temperature experiment illuminates the origins of topology in band structure, and when combined with circuit quantum electrodynamics techniques, it provides a direct path to topologically ordered quantum matter.

  15. Time- and Site-Resolved Dynamics in a Topological Circuit

    Science.gov (United States)

    Ningyuan, Jia; Owens, Clai; Sommer, Ariel; Schuster, David; Simon, Jonathan

    2015-04-01

    From studies of exotic quantum many-body phenomena to applications in spintronics and quantum information processing, topological materials are poised to revolutionize the condensed-matter frontier and the landscape of modern materials science. Accordingly, there is a broad effort to realize topologically nontrivial electronic and photonic materials for fundamental science as well as practical applications. In this work, we demonstrate the first simultaneous site- and time-resolved measurements of a time-reversal-invariant topological band structure, which we realize in a radio-frequency photonic circuit. We control band-structure topology via local permutation of a traveling-wave capacitor-inductor network, increasing robustness by going beyond the tight-binding limit. We observe a gapped density of states consistent with a modified Hofstadter spectrum at a flux per plaquette of ϕ =π /2 . In situ probes of the band gaps reveal spatially localized bulk states and delocalized edge states. Time-resolved measurements reveal dynamical separation of localized edge excitations into spin-polarized currents. The radio-frequency circuit paradigm is naturally compatible with nonlocal coupling schemes, allowing us to implement a Möbius strip topology inaccessible in conventional systems. This room-temperature experiment illuminates the origins of topology in band structure, and when combined with circuit quantum electrodynamics techniques, it provides a direct path to topologically ordered quantum matter.

  16. Dynamic Coding of Signed Quantities in Cortical Feedback Circuits

    Directory of Open Access Journals (Sweden)

    Dana eBallard

    2012-08-01

    Full Text Available In the early sensory and motor areas of the cortex, individual neurons transmit information about specific sensory features via a peaked response. This concept has been crystallized as `labeled lines,' to denote that axons communicate the specific properties of their sensory or motor parent cell. Such cells also can be characterized as being polarized, that is, as representing a signed quantity that is either positive or negative. We show in a model simulation that there are two important consequences when learning receptive fields using such signed codings in circuits that subtract different inputs. The first is that, in feedback circuits using labeled lines, such arithmetic operations need to be distributed across multiple distinct pathways. The second consequence is that such pathways must be necessarily dynamic, i.e. that synapses can grow and retract when forming receptive fields. The model monitors the breaking and growing of new circuit connections when their synapses need to change polarities and predicts that the rate of such changes should be inversely correlated with the progress of receptive field formation.

  17. Dynamic Power Reduction of Digital Circuits by ClockGating

    Directory of Open Access Journals (Sweden)

    Varsha Dewre

    2017-04-01

    Full Text Available In this paper we have presented clock gating process for low power VLSI (very large scale integration circuit design. Clock gating is one of the most quite often used systems in RTL to shrink dynamic power consumption without affecting the performance of the design. One process involves inserting gating requisites in the RTL, which the synthesis tool translates to clock gating cells in the clock-path of a register bank. This helps to diminish the switching activity on the clock network, thereby decreasing dynamic power consumption within the design. Due to the fact the translation accomplished via the synthesis tool is solely combinational; it is referred to as combinational clock gating. This transformation does not alter the behavior of the register being gated

  18. Neural dynamics and circuit mechanisms of decision-making.

    Science.gov (United States)

    Wang, Xiao-Jing

    2012-12-01

    In this review, I briefly summarize current neurobiological studies of decision-making that bear on two general themes. The first focuses on the nature of neural representation and dynamics in a decision circuit. Experimental and computational results suggest that ramping-to-threshold in the temporal domain and trajectory of population activity in the state space represent a duality of perspectives on a decision process. Moreover, a decision circuit can display several different dynamical regimes, such as the ramping mode and the jumping mode with distinct defining properties. The second is concerned with the relationship between biologically-based mechanistic models and normative-type models. A fruitful interplay between experiments and these models at different levels of abstraction have enabled investigators to pose increasingly refined questions and gain new insights into the neural basis of decision-making. In particular, recent work on multi-alternative decisions suggests that deviations from rational models of choice behavior can be explained by established neural mechanisms.

  19. Dynamical Lamb effect versus dissipation in superconducting quantum circuits

    Science.gov (United States)

    Zhukov, A. A.; Shapiro, D. S.; Pogosov, W. V.; Lozovik, Yu. E.

    2016-06-01

    Superconducting circuits provide a new platform for study of nonstationary cavity QED phenomena. An example of such a phenomenon is the dynamical Lamb effect, which is the parametric excitation of an atom due to nonadiabatic modulation of its Lamb shift. This effect was initially introduced for a natural atom in a varying cavity, while we suggest its realization in a superconducting qubit-cavity system with dynamically tunable coupling. In the present paper, we study the interplay between the dynamical Lamb effect and the energy dissipation, which is unavoidable in realistic systems. We find that despite naive expectations, this interplay can lead to unexpected dynamical regimes. One of the most striking results is that photon generation from vacuum can be strongly enhanced due to qubit relaxation, which opens another channel for such a process. We also show that dissipation in the cavity can increase the qubit excited-state population. Our results can be used for experimental observation and investigation of the dynamical Lamb effect and accompanying quantum effects.

  20. Wide Symmetrical Dynamic Range PWM Neuron Circuit with Power Efficient Architecture

    Institute of Scientific and Technical Information of China (English)

    陈继伟; 石秉学

    2002-01-01

    A novel pulse stream neuron circuit is presented whose output pulse width facilitates sigmoid activation to activate the function of neurons. The wide symmetrical dynamic range of this neuron ensures high noise immunity. The pulsed activation strategy provides a power efficient architecture, so the circuit has very low power dissipation. The simplicity of the circuit ensures its suitability for large-scale integration.

  1. Research on dynamic model of printed circuit board based on finite element method

    Science.gov (United States)

    Wei, Hui; Xu, Liangjun

    2017-08-01

    The vibration characteristics of printed circuit boards are related to the reliability of electronic components installed on their surface. Finite element software is a powerful tool to analyze the vibration characteristics of printed circuit boards, and the correct establishment of finite element model is very important. In this paper, the dynamic model of anisotropic printed circuit board is established by analyzing the material properties of printed circuit board. The influence of boundary condition and lumped mass on the vibration characteristics of printed circuit board is analyzed. In order to establish a more realistic printed circuit The finite element model of the plate provides the necessary basis.

  2. Observation of the dynamical Casimir effect in a superconducting circuit

    Science.gov (United States)

    Wilson, Christopher

    2012-02-01

    Modern quantum theory predicts that the vacuum of space is not empty, but instead teeming with virtual particles flitting in and out of existence. While initially a curiosity, it was quickly realized that these vacuum fluctuations had measurable consequences, for instance producing the Lamb shift of atomic spectra and modifying the magnetic moment for the electron. This type of renormalization due to vacuum fluctuations is now central to our understanding of nature. 40 years ago, Moore suggested that a mirror undergoing relativistic motion could convert virtual photons into directly observable real photons. This effect was later named the dynamical Casimir effect (DCE). Using a superconducting circuit, we have observed the DCE for the first time. The circuit consists of a coplanar transmission line with an electrical length that can be changed at a substantial fraction of the speed of light. The length is changed by modulating the inductance of a superconducting quantum interference device (SQUID) at high frequencies (> 10 GHz). In addition to observing the creation of real photons, we observe two-mode squeezing of the emitted radiation, which is a signature of the quantum character of the generation process.

  3. Observation of the Dynamical Casimir Effect in a Superconducting Circuit

    CERN Document Server

    Wilson, C M; Pourkabirian, A; Johansson, J R; Duty, T; Nori, F; Delsing, P

    2011-01-01

    One of the most surprising predictions of modern quantum theory is that the vacuum of space is not empty. In fact, quantum theory predicts that it teems with virtual particles flitting in and out of existence. While initially a curiosity, it was quickly realized that these vacuum fluctuations had measurable consequences, for instance producing the Lamb shift of atomic spectra and modifying the magnetic moment for the electron. This type of renormalization due to vacuum fluctuations is now central to our understanding of nature. However, these effects provide indirect evidence for the existence of vacuum fluctuations. From early on, it was discussed if it might instead be possible to more directly observe the virtual particles that compose the quantum vacuum. 40 years ago, Moore suggested that a mirror undergoing relativistic motion could convert virtual photons into directly observable real photons. This effect was later named the dynamical Casimir effect (DCE). Using a superconducting circuit, we have observ...

  4. Impact of the cell division cycle on gene circuits

    Science.gov (United States)

    Bierbaum, Veronika; Klumpp, Stefan

    2015-12-01

    In growing cells, protein synthesis and cell growth are typically not synchronous, and, thus, protein concentrations vary over the cell division cycle. We have developed a theoretical description of genetic regulatory systems in bacteria that explicitly considers the cell division cycle to investigate its impact on gene expression. We calculate the cell-to-cell variations arising from cells being at different stages in the division cycle for unregulated genes and for basic regulatory mechanisms. These variations contribute to the extrinsic noise observed in single-cell experiments, and are most significant for proteins with short lifetimes. Negative autoregulation buffers against variation of protein concentration over the division cycle, but the effect is found to be relatively weak. Stronger buffering is achieved by an increased protein lifetime. Positive autoregulation can strongly amplify such variation if the parameters are set to values that lead to resonance-like behaviour. For cooperative positive autoregulation, the concentration variation over the division cycle diminishes the parameter region of bistability and modulates the switching times between the two stable states. The same effects are seen for a two-gene mutual-repression toggle switch. By contrast, an oscillatory circuit, the repressilator, is only weakly affected by the division cycle.

  5. Observation of the dynamical Casimir effect in a superconducting circuit.

    Science.gov (United States)

    Wilson, C M; Johansson, G; Pourkabirian, A; Simoen, M; Johansson, J R; Duty, T; Nori, F; Delsing, P

    2011-11-16

    One of the most surprising predictions of modern quantum theory is that the vacuum of space is not empty. In fact, quantum theory predicts that it teems with virtual particles flitting in and out of existence. Although initially a curiosity, it was quickly realized that these vacuum fluctuations had measurable consequences--for instance, producing the Lamb shift of atomic spectra and modifying the magnetic moment of the electron. This type of renormalization due to vacuum fluctuations is now central to our understanding of nature. However, these effects provide indirect evidence for the existence of vacuum fluctuations. From early on, it was discussed whether it might be possible to more directly observe the virtual particles that compose the quantum vacuum. Forty years ago, it was suggested that a mirror undergoing relativistic motion could convert virtual photons into directly observable real photons. The phenomenon, later termed the dynamical Casimir effect, has not been demonstrated previously. Here we observe the dynamical Casimir effect in a superconducting circuit consisting of a coplanar transmission line with a tunable electrical length. The rate of change of the electrical length can be made very fast (a substantial fraction of the speed of light) by modulating the inductance of a superconducting quantum interference device at high frequencies (>10 gigahertz). In addition to observing the creation of real photons, we detect two-mode squeezing in the emitted radiation, which is a signature of the quantum character of the generation process.

  6. Circuit reactivation dynamically regulates synaptic plasticity in neocortex

    Science.gov (United States)

    Kruskal, Peter B.; Li, Lucy; Maclean, Jason N.

    2013-10-01

    Circuit reactivations involve a stereotyped sequence of neuronal firing and have been behaviourally linked to memory consolidation. Here we use multiphoton imaging and patch-clamp recording, and observe sparse and stereotyped circuit reactivations that correspond to UP states within active neurons. To evaluate the effect of the circuit on synaptic plasticity, we trigger a single spike-timing-dependent plasticity (STDP) pairing once per circuit reactivation. The pairings reliably fall within a particular epoch of the circuit sequence and result in long-term potentiation. During reactivation, the amplitude of plasticity significantly correlates with the preceding 20-25 ms of membrane depolarization rather than the depolarization at the time of pairing. This circuit-dependent plasticity provides a natural constraint on synaptic potentiation, regulating the inherent instability of STDP in an assembly phase-sequence model. Subthreshold voltage during endogenous circuit reactivations provides a critical informative context for plasticity and facilitates the stable consolidation of a spatiotemporal sequence.

  7. Dynamic effective connectivity of inter-areal brain circuits.

    Directory of Open Access Journals (Sweden)

    Demian Battaglia

    Full Text Available Anatomic connections between brain areas affect information flow between neuronal circuits and the synchronization of neuronal activity. However, such structural connectivity does not coincide with effective connectivity (or, more precisely, causal connectivity, related to the elusive question "Which areas cause the present activity of which others?". Effective connectivity is directed and depends flexibly on contexts and tasks. Here we show that dynamic effective connectivity can emerge from transitions in the collective organization of coherent neural activity. Integrating simulation and semi-analytic approaches, we study mesoscale network motifs of interacting cortical areas, modeled as large random networks of spiking neurons or as simple rate units. Through a causal analysis of time-series of model neural activity, we show that different dynamical states generated by a same structural connectivity motif correspond to distinct effective connectivity motifs. Such effective motifs can display a dominant directionality, due to spontaneous symmetry breaking and effective entrainment between local brain rhythms, although all connections in the considered structural motifs are reciprocal. We show then that transitions between effective connectivity configurations (like, for instance, reversal in the direction of inter-areal interactions can be triggered reliably by brief perturbation inputs, properly timed with respect to an ongoing local oscillation, without the need for plastic synaptic changes. Finally, we analyze how the information encoded in spiking patterns of a local neuronal population is propagated across a fixed structural connectivity motif, demonstrating that changes in the active effective connectivity regulate both the efficiency and the directionality of information transfer. Previous studies stressed the role played by coherent oscillations in establishing efficient communication between distant areas. Going beyond these early

  8. Dynamic Effective Connectivity of Inter-Areal Brain Circuits

    Science.gov (United States)

    Battaglia, Demian; Witt, Annette; Wolf, Fred; Geisel, Theo

    2012-01-01

    Anatomic connections between brain areas affect information flow between neuronal circuits and the synchronization of neuronal activity. However, such structural connectivity does not coincide with effective connectivity (or, more precisely, causal connectivity), related to the elusive question “Which areas cause the present activity of which others?”. Effective connectivity is directed and depends flexibly on contexts and tasks. Here we show that dynamic effective connectivity can emerge from transitions in the collective organization of coherent neural activity. Integrating simulation and semi-analytic approaches, we study mesoscale network motifs of interacting cortical areas, modeled as large random networks of spiking neurons or as simple rate units. Through a causal analysis of time-series of model neural activity, we show that different dynamical states generated by a same structural connectivity motif correspond to distinct effective connectivity motifs. Such effective motifs can display a dominant directionality, due to spontaneous symmetry breaking and effective entrainment between local brain rhythms, although all connections in the considered structural motifs are reciprocal. We show then that transitions between effective connectivity configurations (like, for instance, reversal in the direction of inter-areal interactions) can be triggered reliably by brief perturbation inputs, properly timed with respect to an ongoing local oscillation, without the need for plastic synaptic changes. Finally, we analyze how the information encoded in spiking patterns of a local neuronal population is propagated across a fixed structural connectivity motif, demonstrating that changes in the active effective connectivity regulate both the efficiency and the directionality of information transfer. Previous studies stressed the role played by coherent oscillations in establishing efficient communication between distant areas. Going beyond these early proposals, we

  9. Biologic: Gene circuits and feedback in an introductory physics sequence for biology and premedical students

    CERN Document Server

    Cahn, S B

    2013-01-01

    Two synthetic gene circuits -- the genetic toggle switch and the repressilator -- are analyzed quantitatively and discussed in the context of an educational module on gene circuits and feedback that constitutes the final topic of a year-long introductory physics sequence, aimed at biology and premedical undergraduate students. The genetic toggle switch consists of two genes, each of whose protein product represses the other's expression, while the repressilator consists of three genes, each of whose protein product represses the next gene's expression. Analytic, numerical, and electronic treatments of the genetic toggle switch shows that this gene circuit realizes bistability. A simplified treatment of the repressilator reveals that this circuit can realize sustained oscillations. In both cases, a "phase diagram" is obtained, that specifies the region of parameter space in which bistability or oscillatory behavior, respectively, occurs.

  10. p53 activated by AND gate genetic circuit under radiation and hypoxia for targeted cancer gene therapy.

    Science.gov (United States)

    Ding, Miao; Li, Rong; He, Rong; Wang, Xingyong; Yi, Qijian; Wang, Weidong

    2015-09-01

    Radio-activated gene therapy has been developed as a novel therapeutic strategy against cancer; however, expression of therapeutic gene in peritumoral tissues will result in unacceptable toxicity to normal cells. To restrict gene expression in targeted tumor mass, we used hypoxia and radiation tolerance features of tumor cells to develop a synthetic AND gate genetic circuit through connecting radiation sensitivity promoter cArG6 , heat shock response elements SNF1, HSF1 and HSE4 with retroviral vector plxsn. Their construction and dynamic activity process were identified through downstream enhanced green fluorescent protein and wtp53 expression in non-small cell lung cancer A549 cells and in a nude mice model. The result showed that AND gate genetic circuit could be activated by lower required radiation dose (6 Gy) and after activated, AND gate could induce significant apoptosis effects and growth inhibition of cancer cells in vitro and in vivo. The radiation- and hypoxia-activated AND gate genetic circuit, which could lead to more powerful target tumoricidal activity represented a promising strategy for both targeted and effective gene therapy of human lung adenocarcinoma and low dose activation character of the AND gate genetic circuit implied that this model could be further exploited to decrease side-effects of clinical radiation therapy.

  11. Accurate dynamic power estimation for CMOS combinational logic circuits with real gate delay model

    Directory of Open Access Journals (Sweden)

    Omnia S. Fadl

    2016-01-01

    Full Text Available Dynamic power estimation is essential in designing VLSI circuits where many parameters are involved but the only circuit parameter that is related to the circuit operation is the nodes’ toggle rate. This paper discusses a deterministic and fast method to estimate the dynamic power consumption for CMOS combinational logic circuits using gate-level descriptions based on the Logic Pictures concept to obtain the circuit nodes’ toggle rate. The delay model for the logic gates is the real-delay model. To validate the results, the method is applied to several circuits and compared against exhaustive, as well as Monte Carlo, simulations. The proposed technique was shown to save up to 96% processing time compared to exhaustive simulation.

  12. An investigation of algebraic quantum dynamics for mesoscopic coupled electric circuits with mutual inductance

    Energy Technology Data Exchange (ETDEWEB)

    Pahlavani, H., E-mail: h-pahlavani@qom.ac.ir; Kolur, E. Rahmanpour

    2016-08-15

    Based on the electrical charge discreteness, the Hamiltonian operator for the mutual inductance coupled quantum mesoscopic LC circuits has been found. The persistent current on two driven coupled mesoscopic electric pure L circuits (two quantum loops) has been obtained by using algebraic quantum dynamic approach. The influence of the mutual inductance on energy spectrum and quantum fluctuations of the charge and current for two coupled quantum electric mesoscopic LC circuits have been investigated.

  13. Analysis and design of a genetic circuit for dynamic metabolic engineering.

    Science.gov (United States)

    Anesiadis, Nikolaos; Kobayashi, Hideki; Cluett, William R; Mahadevan, Radhakrishnan

    2013-08-16

    Recent advances in synthetic biology have equipped us with new tools for bioprocess optimization at the genetic level. Previously, we have presented an integrated in silico design for the dynamic control of gene expression based on a density-sensing unit and a genetic toggle switch. In the present paper, analysis of a serine-producing Escherichia coli mutant shows that an instantaneous ON-OFF switch leads to a maximum theoretical productivity improvement of 29.6% compared to the mutant. To further the design, global sensitivity analysis is applied here to a mathematical model of serine production in E. coli coupled with a genetic circuit. The model of the quorum sensing and the toggle switch involves 13 parameters of which 3 are identified as having a significant effect on serine concentration. Simulations conducted in this reduced parameter space further identified the optimal ranges for these 3 key parameters to achieve productivity values close to the maximum theoretical values. This analysis can now be used to guide the experimental implementation of a dynamic metabolic engineering strategy and reduce the time required to design the genetic circuit components.

  14. Positive circuits and maximal number of fixed points in discrete dynamical systems

    CERN Document Server

    Richard, Adrien

    2008-01-01

    The biologist Ren\\'e Thomas conjectured, twenty years ago, that the presence of a positive circuit in the interaction graph of a dynamical system is a necessary condition for the presence of multiple stable states. Recently, Richard and Comet stated and proved this conjecture for systems whose dynamics is described by the iterations of a map $F$ which operates on the product $X$ of $n$ finite intervals of integers. In this paper, we widely extend the result of Richard and Comet by exhibiting an upper bound on the number of fixed points for $F$ which only depends on $X$ and on the topology of the positive circuits of the interaction graph associated with $F$. Our motivation for this work comes from biology. The maps $F$ we focus on are indeed extensively used to described the behavior of gene regulatory networks, and when such a network is studied, the first reliable data often concern its interaction graph, so that the bound we establish can be used, in practice, to obtain valuable information about the numbe...

  15. Dynamic companion harmonic circuit models for analysis of power systems with embedded power electronics devices

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, H.; Madrigal, M. [Programa de Graduados e Investigacion en Ingenieria Electrica, Instituto Tecnologico de Morelia, Morelia (Mexico); Vyakaranam, B.; Rarick, R.; Villaseca, F.E. [Department of Electrical and Computer Engineering, Cleveland State University, OH (United States)

    2011-02-15

    In this paper a methodology that extends the dynamic harmonic domain (DHD) analysis of large networks is presented. The method combines DHD analysis and discrete companion circuit modeling resulting in a powerful analytic technique called dynamic companion harmonic circuit modeling. It provides for a complete dynamic harmonic analysis of the system while preserving the advantages of discrete companion circuit models. The methodology is illustrated by its application to a three-node power system, where reactive power compensation is achieved using a fixed-capacitor, thyristor-controlled reactor (FC-TCR) and its control system. (author)

  16. Simulation and Analysis of Dynamic Characteristics of3D Assembly Circuit Module with Finite Element Method

    Institute of Scientific and Technical Information of China (English)

    黄春跃; 周德俭; 黄红艳

    2004-01-01

    Based on the modal analysis theory and by using the dynamics finite element analysis model of a three-dimensional assembly circuit module, dynamic characteristics of circuit module have been studied, including both natural characteristics analysis and dynamic responses analysis. Using a subspace method, modal analysis is first carried out. The first 6 orders of natural frequencies and vibration modes are obtained. Influence of the number of the Z-shaped metal slices on dynamic characteristics of the entire structure is also studied.Harmonic response analysis is then conducted. The steady-state response when the circuit module is subjected to harmonic excitation is determined. A curve of the response values against frequencies is obtained. As a result, the optimal number of Z-shaped metal slices can be determined, and it can be assured that the three-dimensional assembly circuit module has good performance in terms of the dynamic characteristics.

  17. Dynamic modeling and analysis of the closed-circuit grinding-classification process

    Institute of Scientific and Technical Information of China (English)

    Yunfei Chu; Wenli Xu; Weihan Wan

    2005-01-01

    Mathematical models of the grinding process are the basis of analysis, simulation and control. Most existent models including theoretical models and identification models are, however, inconvenient for direct analysis. In addition, many models pay much attention to the local details in the closed-circuit grinding process while overlooking the systematic behavior of the process as a whole. From the systematic perspective, the dynamic behavior of the whole closed-circuit grinding-classification process is considered and a first-order transfer function model describing the dynamic relation between the raw material and the product is established.The model proves that the time constant of the closed-circuit process is lager than that of the open-circuit process and reveals how physical parameters affect the process dynamic behavior. These are very helpful to understand, design and control the closed-circuit grinding-classification process.

  18. Optimized Second-Order Dynamical Systems and Their RLC Circuit Models with PWL Controlled Sources

    Directory of Open Access Journals (Sweden)

    J. Brzobohaty

    2004-09-01

    Full Text Available Complementary active RLC circuit models with a voltage-controlledvoltage source (VCVS and a current-controlled current source (CCCSfor the second-order autonomous dynamical system realization areproposed. The main advantage of these equivalent circuits is the simplerelation between the state model parameters and their correspondingcircuit parameters, which leads also to simple design formulas.

  19. Boolean network model for GPR142 against Type 2 diabetes and relative dynamic change ratio analysis using systems and biological circuits approach.

    Science.gov (United States)

    Kaushik, Aman Chandra; Sahi, Shakti

    2015-06-01

    Systems biology addresses challenges in the analysis of genomics data, especially for complex genes and protein interactions using Meta data approach on various signaling pathways. In this paper, we report systems biology and biological circuits approach to construct pathway and identify early gene and protein interactions for predicting GPR142 responses in Type 2 diabetes. The information regarding genes, proteins and other molecules involved in Type 2 diabetes were retrieved from literature and kinetic simulation of GPR142 was carried out in order to determine the dynamic interactions. The major objective of this work was to design a GPR142 biochemical pathway using both systems biology as well as biological circuits synthetically. The term 'synthetically' refers to building biological circuits for cell signaling pathway especially for hormonal pathway disease. The focus of the paper is on logical components and logical circuits whereby using these applications users can create complex virtual circuits. Logic gates process represents only true or false and investigates whether biological regulatory circuits are active or inactive. The basic gates used are AND, NAND, OR, XOR and NOT gates and Integrated circuit composition of many such basic gates and some derived gates. Biological circuits may have a futuristic application in biomedical sciences which may involve placing a micro chip in human cells to modulate the down or up regulation of hormonal disease.

  20. An Overview of Dynamic Contact Resistance Measurement of HV Circuit Breakers

    Science.gov (United States)

    Bhole, A. A.; Gandhare, W. Z.

    2016-06-01

    With the deregulation of the electrical power industry, utilities and service companies are operating in a changing business environment. High voltage circuit breakers are extremely important for the function of modern electric power supply systems. The need to predict the proper function of circuit breaker grew over the years as the transmission networks expanded. The maintenance of circuit breakers deserves special consideration because of their importance for routine switching and for protection of other equipments. Electric transmission system breakups and equipment destruction can occur if a circuit breaker fails to operate because of a lack of preventive maintenance. Dynamic Contact Resistance Measurement (DCRM) is known as an effective technique for assessing the condition of power circuit breakers contacts and operating mechanism. This paper gives a general review about DCRM. It discusses the practical case studies on use of DCRM for condition assessment of high voltage circuit breakers.

  1. D-VASim: Dynamic Virtual Analyzer and Simulator for Genetic Circuits

    DEFF Research Database (Denmark)

    Baig, Hasan; Madsen, Jan

    2015-01-01

    A genetic circuit represents a gene regulator network that is triggered by a combination of external signals, such as chemicals, proteins, light or temperature, to emit signals to control gene expression or metabolic pathways accordingly. In order to match the intended behaviour, genetic circuits......, with the aim to reduce the number of required in-vitro experiments. We present a behavioural simulation and analysis tool that allows the biologist to carry out virtual lab experiments as an interactive process during simulation of the genetic circuit, rather than a batch process, which is current practice. We...

  2. Development of a Dynamic Population Balance Plant Simulator for Mineral Processing Circuits

    Directory of Open Access Journals (Sweden)

    Fatemeh Khoshnam

    2015-06-01

    Full Text Available Operational variables of a mineral processing circuit are subjected to different variations. Steady-statesimulation of processes provides an estimate of their ideal stable performance whereas their dynamicsimulation predicts the effects of the variations on the processes or their subsequent processes. In thispaper, a dynamic simulator containing some of the major equipment of mineral processing circuits(i.e. ball mill, cone crusher, screen, hydrocyclone, mechanical flotation cell, tank leaching andconveyor belt was developed. The dynamic simulator of each mentioned unit was also developedaccording to population balance models with the help of MATLAB/Simulink environment and wasverified against the data from the literature. Comminution and separation sections were linked usingempirical models which correlate the separation and extraction kinetics to particle size. Applying thedeveloped simulator, the dynamic behavior of a grinding-leaching circuit was analyzed and the resultsshowed that such simulations are required for both designing and controlling the circuits.

  3. Parts & pools: a framework for modular design of synthetic gene circuits.

    Science.gov (United States)

    Marchisio, Mario Andrea

    2014-01-01

    Published in 2008, Parts & Pools represents one of the first attempts to conceptualize the modular design of bacterial synthetic gene circuits with Standard Biological Parts (DNA segments) and Pools of molecules referred to as common signal carriers (e.g., RNA polymerases and ribosomes). The original framework for modeling bacterial components and designing prokaryotic circuits evolved over the last years and brought, first, to the development of an algorithm for the automatic design of Boolean gene circuits. This is a remarkable achievement since gene digital circuits have a broad range of applications that goes from biosensors for health and environment care to computational devices. More recently, Parts & Pools was enabled to give a proper formal description of eukaryotic biological circuit components. This was possible by employing a rule-based modeling approach, a technique that permits a faithful calculation of all the species and reactions involved in complex systems such as eukaryotic cells and compartments. In this way, Parts & Pools is currently suitable for the visual and modular design of synthetic gene circuits in yeast and mammalian cells too.

  4. Design of High Performance Dynamic CMOS Circuits in Deep Submicron Technology

    Directory of Open Access Journals (Sweden)

    Salendra.Govindarajulu

    2010-07-01

    Full Text Available Technology scaling of transistor feature size has provided a remarkable advancement in silicon industry for the last three decades. The demand and popularity of portable electronics is driving designers to strive for small silicon area, higher speeds, low power dissipation and reliability. Compared to static CMOS logic, dynamic logic offers good performance. Wide fan-in logic such as domino circuits is used in high-performance applications. Dynamic domino logic circuits are widely used in modern digital VLSI circuits. These dynamic circuits are often favoured in high performance designs because of the speed advantage offered over static CMOS logic circuits. This paper compares static CMOS, domino (dynamic logic design implementations of 16-bit Ripple carry adder, 16-bit Comparator and Linear Feedback Shift Register (LFSR in terms of CMOS layout power consumption, delay, power delay product, area for 65 nm and 45 nm technologies. The techniques are compared by performing detailed transistor simulations on benchmark circuits using Microwind 3 and DSCH3 CMOS layout CAD tools.

  5. Dissecting differential gene expression within the circadian neuronal circuit of Drosophila

    Science.gov (United States)

    Nagoshi, Emi; Sugino, Ken; Kula, Ela; Okazaki, Etsuko; Tachibana, Taro; Nelson, Sacha; Rosbash, Michael

    2013-01-01

    Behavioral circadian rhythms are controlled by a neuronal circuit consisting of diverse neuronal subgroups. To understand the molecular mechanisms underlying the roles of neuronal subgroups within the Drosophila circadian circuit, we used cell-type specific gene-expression profiling and identified a large number of genes specifically expressed in all clock neurons or in two important subgroups. Moreover, we identified and characterized two circadian genes, which are expressed specifically in subsets of clock cells and affect different aspects of rhythms. The transcription factor Fer2 is expressed in ventral lateral neurons; it is required for the specification of lateral neurons and therefore their ability to drive locomotor rhythms. The Drosophila melanogaster homolog of the vertebrate circadian gene nocturnin is expressed in a subset of dorsal neurons and mediates the circadian light response. The approach should also enable the molecular dissection of many different Drosophila neuronal circuits. PMID:19966839

  6. Research of time discrimination circuits for PMT signal readout over large dynamic range in LHAASO WCDA

    Science.gov (United States)

    Ma, C.; Zhao, L.; Dong, R.; Jiang, Z.; Chu, S.; Gao, X.; Liu, S.; An, Q.

    2016-11-01

    In the readout electronics of the Water Cerenkov Detector Array (WCDA) in the Large High Altitude Air Shower Observatory (LHAASO), both high-resolution charge and time measurement are required over a dynamic range from 1 photoelectron (P.E.) to 4000 P.E. for the PMT signal readout. In this paper, we present our work on the design of time discrimination circuits in LHAASO WCDA, especially on improvement to reduce the circuit dead time. Several approaches were studied through analysis and simulations, and actual circuits were designed and tested in the laboratory to evaluate the performance. Test results indicate that a time resolution better than 500 ps RMS is achieved in the whole large dynamic range, and the circuit dead time is successfully reduced to less than 200 ns.

  7. Hacking DNA copy number for circuit engineering.

    Science.gov (United States)

    Wu, Feilun; You, Lingchong

    2017-07-27

    DNA copy number represents an essential parameter in the dynamics of synthetic gene circuits but typically is not explicitly considered. A new study demonstrates how dynamic control of DNA copy number can serve as an effective strategy to program robust oscillations in gene expression circuits.

  8. Dynamical bistability in driven Josephson circuits - the WKB limit and beyond.

    Energy Technology Data Exchange (ETDEWEB)

    Peano, Vittorio; Thorwart, Michael [FRIAS Albert-Ludwigs-Universitaet, Freiburg (Germany)

    2010-07-01

    Driven and dissipative nonlinear quantum oscillators can be operated in a regime where a bistability is induced dynamically. Prominent examples are the Josephson bifurcation amplifier and the driven circuit QED set-up of the superconducting transmon qubit. Josephson circuits with their large quality factors and scalable nonlinearities are the perfect playground to explore this phenomenon from the classical limit down to the quantum scale. We show that the WKB approximation is an excellent tool in all these regimes. We explore its limit of validity, focusing thereby on the quantum Duffing oscillator and the driven circuit QED.

  9. Design of Timer Circuit for Dynamic Data System

    Science.gov (United States)

    Young, Nathaniel, III

    2004-01-01

    The Branch That I work in is in the Aero Electronic Test Branch, which is part of the Research and Testing Division. The Aero Electronic Test Branch deals with electronic control and instrumentation systems. This branch supports the research and test study of wind tunnels such as the l0x10,9x15, and 8x6. Wind tunnels are used in research to test certain parts of a jet, plane, shuttle or any other flying object in certain test conditions. My assignment is to design a programmable trigger circuit on a 19 standard rack mount that will allow the circuit to latch and hold for a predefined amount of time entered by the user when receiving a signal. It should then re-arm itself within 0.25 seconds after the time is finished. The time should be able to be seen on a display showing the time entered. The time range has to be from 0-600 seconds in 0.01 second increments (600.00). From the information given, counters will be needed to design and build this circuit. A counter, in it s simplest form, is a group of flip flops that can temporarily store bits of information put into the circuit. They can be constructed in many different ways, such as in 4 flip flops (4-bit counter) or 8 flip flops and even higher. Counters are usually cascaded with other counters to reach higher bits, such as 16 or 24 bit counters. The application in which I will use the counters will be to count down from any programmable number that I input either by a keyboard or a thumbwheel. Also, I will use counters that will be used specifically as a frequency divider to divide the pulses that enter the circuit through an input signal from a crystal clock. The pulses will need to be divided so that it will function as a 100Hz clock putting out 100 pulses per second. A switch will be used to load my inputs in and more than likely a button also so that I can stop and hold the count at any point of time. I will use 5 BCD up/down programmable counters, and a certain amount (depending on what kind of "divide by N

  10. A recursive network approach can identify constitutive regulatory circuits in gene expression data

    Science.gov (United States)

    Blasi, Monica Francesca; Casorelli, Ida; Colosimo, Alfredo; Blasi, Francesco Simone; Bignami, Margherita; Giuliani, Alessandro

    2005-03-01

    The activity of the cell is often coordinated by the organisation of proteins into regulatory circuits that share a common function. Genome-wide expression profiles might contain important information on these circuits. Current approaches for the analysis of gene expression data include clustering the individual expression measurements and relating them to biological functions as well as modelling and simulation of gene regulation processes by additional computer tools. The identification of the regulative programmes from microarray experiments is limited, however, by the intrinsic difficulty of linear methods to detect low-variance signals and by the sensitivity of the different approaches. Here we face the problem of recognising invariant patterns of correlations among gene expression reminiscent of regulation circuits. We demonstrate that a recursive neural network approach can identify genetic regulation circuits from expression data for ribosomal and genome stability genes. The proposed method, by greatly enhancing the sensitivity of microarray studies, allows the identification of important aspects of genetic regulation networks and might be useful for the discrimination of the different players involved in regulation circuits. Our results suggest that the constitutive regulatory networks involved in the generic organisation of the cell display a high degree of clustering depending on a modular architecture.

  11. Automatic design of synthetic gene circuits through mixed integer non-linear programming.

    Science.gov (United States)

    Huynh, Linh; Kececioglu, John; Köppe, Matthias; Tagkopoulos, Ilias

    2012-01-01

    Automatic design of synthetic gene circuits poses a significant challenge to synthetic biology, primarily due to the complexity of biological systems, and the lack of rigorous optimization methods that can cope with the combinatorial explosion as the number of biological parts increases. Current optimization methods for synthetic gene design rely on heuristic algorithms that are usually not deterministic, deliver sub-optimal solutions, and provide no guaranties on convergence or error bounds. Here, we introduce an optimization framework for the problem of part selection in synthetic gene circuits that is based on mixed integer non-linear programming (MINLP), which is a deterministic method that finds the globally optimal solution and guarantees convergence in finite time. Given a synthetic gene circuit, a library of characterized parts, and user-defined constraints, our method can find the optimal selection of parts that satisfy the constraints and best approximates the objective function given by the user. We evaluated the proposed method in the design of three synthetic circuits (a toggle switch, a transcriptional cascade, and a band detector), with both experimentally constructed and synthetic promoter libraries. Scalability and robustness analysis shows that the proposed framework scales well with the library size and the solution space. The work described here is a step towards a unifying, realistic framework for the automated design of biological circuits.

  12. Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits.

    Science.gov (United States)

    Kononenko, Olga; Galatenko, Vladimir; Andersson, Malin; Bazov, Igor; Watanabe, Hiroyuki; Zhou, Xing Wu; Iatsyshyna, Anna; Mityakina, Irina; Yakovleva, Tatiana; Sarkisyan, Daniil; Ponomarev, Igor; Krishtal, Oleg; Marklund, Niklas; Tonevitsky, Alex; Adkins, DeAnna L; Bakalkin, Georgy

    2017-01-25

    Regulation of the formation and rewiring of neural circuits by neuropeptides may require coordinated production of these signaling molecules and their receptors that may be established at the transcriptional level. Here, we address this hypothesis by comparing absolute expression levels of opioid peptides with their receptors, the largest neuropeptide family, and by characterizing coexpression (transcriptionally coordinated) patterns of these genes. We demonstrated that expression patterns of opioid genes highly correlate within and across functionally and anatomically different areas. Opioid peptide genes, compared with their receptor genes, are transcribed at much greater absolute levels, which suggests formation of a neuropeptide cloud that covers the receptor-expressed circuits. Surprisingly, we found that both expression levels and the proportion of opioid receptors are strongly lateralized in the spinal cord, interregional coexpression patterns are side-specific, and intraregional coexpression profiles are affected differently by left- and right-side unilateral body injury. We propose that opioid genes are regulated as interconnected components of the same molecular system distributed between distinct anatomic regions. The striking feature of this system is its asymmetric coexpression patterns, which suggest side-specific regulation of selective neural circuits by opioid neurohormones.-Kononenko, O., Galatenko, V., Andersson, M., Bazov, I., Watanabe, H., Zhou, X. W., Iatsyshyna, A., Mityakina, I., Yakovleva, T., Sarkisyan, D., Ponomarev, I., Krishtal, O., Marklund, N., Tonevitsky, A., Adkins, D. L., Bakalkin, G. Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits.

  13. Dynamic circuit and Fourier series methods for moment calculation in electrodynamic repulsive magnetic levitation systems

    Science.gov (United States)

    Knowles, R.

    1982-07-01

    A general theory of moments for electrodynamic magnetic levitation systems has been developed using double Fourier series and dynamic circuit principles. Both employ Parseval's theorem using either wave constant derivatives or the polar waveconstant principle of the Fourier-Bessel/double Fourier series equivalence. A method for calculating angular derivatives of moments and forces is explained, and for all of these methods comparisons are made with experimental results obtained for single and split rail configurations. Extensions of dynamic circuit theory for tilted nonflat and circular magnets are also explained.

  14. A dynamic resistance nonuniformity compensation circuit for uncooled microbolometer detector arrays

    Science.gov (United States)

    Yildirim, Omer Ozgur; Akin, Tayfun

    2006-05-01

    This paper presents a new approach for compensating resistance nonuniformity of uncooled microbolometers by adjusting the bias currents of both detector and reference pixels. Contrary to conventional nonuniformity compensation circuits, this approach eliminates the need for digital-to-analog converters (DACs), which usually occupy a large area, dissipate high power, and require complicated external circuitry with high frequency data transfer to the microbolometer chip. The proposed circuit uses a feedback structure that dynamically changes the bias currents of the reference and detector pixels and does not need complicated external circuitry. A special feature of the circuit is that it provides continuous compensation for the detector and reference resistances due to temperature changes over time. The circuit is implemented in a 0.6μm 5V CMOS process and occupies an area of only 160μm × 630μm. Test results of the prototype circuit show that the circuit reduces the offset current due to resistance nonuniformity about 2.35% of its uncompensated value, i.e., an improvement of about 42.5 times is achieved, independent of the nonuniformity amount. The circuit achieves this compensation in 12μsec. Considering its simplicity and low cost, this approach is suitable for large array commercial infrared imaging systems.

  15. Geometric reduction of dynamical nonlocality in nanoscale quantum circuits

    Science.gov (United States)

    Strambini, E.; Makarenko, K. S.; Abulizi, G.; de Jong, M. P.; van der Wiel, W. G.

    2016-01-01

    Nonlocality is a key feature discriminating quantum and classical physics. Quantum-interference phenomena, such as Young’s double slit experiment, are one of the clearest manifestations of nonlocality, recently addressed as dynamical to specify its origin in the quantum equations of motion. It is well known that loss of dynamical nonlocality can occur due to (partial) collapse of the wavefunction due to a measurement, such as which-path detection. However, alternative mechanisms affecting dynamical nonlocality have hardly been considered, although of crucial importance in many schemes for quantum information processing. Here, we present a fundamentally different pathway of losing dynamical nonlocality, demonstrating that the detailed geometry of the detection scheme is crucial to preserve nonlocality. By means of a solid-state quantum-interference experiment we quantify this effect in a diffusive system. We show that interference is not only affected by decoherence, but also by a loss of dynamical nonlocality based on a local reduction of the number of quantum conduction channels of the interferometer. With our measurements and theoretical model we demonstrate that this mechanism is an intrinsic property of quantum dynamics. Understanding the geometrical constraints protecting nonlocality is crucial when designing quantum networks for quantum information processing.

  16. Geometric reduction of dynamical nonlocality in nanoscale quantum circuits

    Science.gov (United States)

    Strambini, E.; Makarenko, K. S.; Abulizi, G.; de Jong, M. P.; van der Wiel, W. G.

    2016-01-01

    Nonlocality is a key feature discriminating quantum and classical physics. Quantum-interference phenomena, such as Young’s double slit experiment, are one of the clearest manifestations of nonlocality, recently addressed as dynamical to specify its origin in the quantum equations of motion. It is well known that loss of dynamical nonlocality can occur due to (partial) collapse of the wavefunction due to a measurement, such as which-path detection. However, alternative mechanisms affecting dynamical nonlocality have hardly been considered, although of crucial importance in many schemes for quantum information processing. Here, we present a fundamentally different pathway of losing dynamical nonlocality, demonstrating that the detailed geometry of the detection scheme is crucial to preserve nonlocality. By means of a solid-state quantum-interference experiment we quantify this effect in a diffusive system. We show that interference is not only affected by decoherence, but also by a loss of dynamical nonlocality based on a local reduction of the number of quantum conduction channels of the interferometer. With our measurements and theoretical model we demonstrate that this mechanism is an intrinsic property of quantum dynamics. Understanding the geometrical constraints protecting nonlocality is crucial when designing quantum networks for quantum information processing. PMID:26732751

  17. Laser dynamics: The system dynamics and network theory of optoelectronic integrated circuit design

    Science.gov (United States)

    Tarng, Tom Shinming-T. K.

    Laser dynamics is the system dynamics, communication and network theory for the design of opto-electronic integrated circuit (OEIC). Combining the optical network theory and optical communication theory, the system analysis and design for the OEIC fundamental building blocks is considered. These building blocks include the direct current modulation, inject light modulation, wideband filter, super-gain optical amplifier, E/O and O/O optical bistability and current-controlled optical oscillator. Based on the rate equations, the phase diagram and phase portrait analysis is applied to the theoretical studies and numerical simulation. The OEIC system design methodologies are developed for the OEIC design. Stimulating-field-dependent rate equations are used to model the line-width narrowing/broadening mechanism for the CW mode and frequency chirp of semiconductor lasers. The momentary spectra are carrier-density-dependent. Furthermore, the phase portrait analysis and the nonlinear refractive index is used to simulate the single mode frequency chirp. The average spectra of chaos, period doubling, period pulsing, multi-loops and analog modulation are generated and analyzed. The bifurcation-chirp design chart with modulation depth and modulation frequency as parameters is provided for design purpose.

  18. Dynamic stability of inner windings of large capacity transformers under short-circuit conditions

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Presents the study on the dynamic buckling of the inner windings of large capacity transformers under short circuit conditions by a finite element method and the findings as follows: 1) No radial dynamic buckling of inner windings occurs under short-circuit conditions when the windings are well supported at all the radial supports; 2) The windings buckle under short-circuit conditions when the windings are not supported at one radial support (for instance, 25°) but well supported at all other radial supports; 3) When the windings are not well supported at one radial support, the ability of the windings to resist radial dy namic buckling can be greatly enhanced provided some measures are taken to provide necessary radial supporting.

  19. Dynamical systems, attractors, and neural circuits [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Paul Miller

    2016-05-01

    Full Text Available Biology is the study of dynamical systems. Yet most of us working in biology have limited pedagogical training in the theory of dynamical systems, an unfortunate historical fact that can be remedied for future generations of life scientists. In my particular field of systems neuroscience, neural circuits are rife with nonlinearities at all levels of description, rendering simple methodologies and our own intuition unreliable. Therefore, our ideas are likely to be wrong unless informed by good models. These models should be based on the mathematical theories of dynamical systems since functioning neurons are dynamic—they change their membrane potential and firing rates with time. Thus, selecting the appropriate type of dynamical system upon which to base a model is an important first step in the modeling process. This step all too easily goes awry, in part because there are many frameworks to choose from, in part because the sparsely sampled data can be consistent with a variety of dynamical processes, and in part because each modeler has a preferred modeling approach that is difficult to move away from. This brief review summarizes some of the main dynamical paradigms that can arise in neural circuits, with comments on what they can achieve computationally and what signatures might reveal their presence within empirical data. I provide examples of different dynamical systems using simple circuits of two or three cells, emphasizing that any one connectivity pattern is compatible with multiple, diverse functions.

  20. Atomic physics and quantum optics using superconducting circuits: from the Dynamical Casimir effect to Majorana fermions

    Science.gov (United States)

    Nori, Franco

    2012-02-01

    This talk will present an overview of some of our recent results on atomic physics and quantum optics using superconducting circuits. Particular emphasis will be given to photons interacting with qubits, interferometry, the Dynamical Casimir effect, and also studying Majorana fermions using superconducting circuits.[4pt] References available online at our web site:[0pt] J.Q. You, Z.D. Wang, W. Zhang, F. Nori, Manipulating and probing Majorana fermions using superconducting circuits, (2011). Arxiv. J.R. Johansson, G. Johansson, C.M. Wilson, F. Nori, Dynamical Casimir effect in a superconducting coplanar waveguide, Phys. Rev. Lett. 103, 147003 (2009). [0pt] J.R. Johansson, G. Johansson, C.M. Wilson, F. Nori, Dynamical Casimir effect in superconducting microwave circuits, Phys. Rev. A 82, 052509 (2010). [0pt] C.M. Wilson, G. Johansson, A. Pourkabirian, J.R. Johansson, T. Duty, F. Nori, P. Delsing, Observation of the Dynamical Casimir Effect in a superconducting circuit. Nature, in press (Nov. 2011). P.D. Nation, J.R. Johansson, M.P. Blencowe, F. Nori, Stimulating uncertainty: Amplifying the quantum vacuum with superconducting circuits, Rev. Mod. Phys., in press (2011). [0pt] J.Q. You, F. Nori, Atomic physics and quantum optics using superconducting circuits, Nature 474, 589 (2011). [0pt] S.N. Shevchenko, S. Ashhab, F. Nori, Landau-Zener-Stuckelberg interferometry, Phys. Reports 492, 1 (2010). [0pt] I. Buluta, S. Ashhab, F. Nori. Natural and artificial atoms for quantum computation, Reports on Progress in Physics 74, 104401 (2011). [0pt] I.Buluta, F. Nori, Quantum Simulators, Science 326, 108 (2009). [0pt] L.F. Wei, K. Maruyama, X.B. Wang, J.Q. You, F. Nori, Testing quantum contextuality with macroscopic superconducting circuits, Phys. Rev. B 81, 174513 (2010). [0pt] J.Q. You, X.-F. Shi, X. Hu, F. Nori, Quantum emulation of a spin system with topologically protected ground states using superconducting quantum circuit, Phys. Rev. A 81, 063823 (2010).

  1. Dynamic Simulation and Opening Bouncing Analysis of Vacuum Circuit Breaker with Permanent Magnetic Actuator

    Institute of Scientific and Technical Information of China (English)

    LIN Xin; CAO Chen; LI Bin; LIU Yang; XU Jianyuan

    2013-01-01

    In order to research the dynamic characteristics of circuit breaker (CB) in opening process,taking a 12 kV vacuum circuit breaker (VCB) with permanent magnetic actuator as the example,a dynamic model of the VCB is established based on the virtual prototype technology,and dynamic equations of the model are deduced.Simulation and experiment are carried out on the VCB of both opening and closing processes.The simulative opening time and closing time are 39.5 ms and 54.6 ms respectively.Influencing factors of opening bouncing and their effect principles are analyzed through dynamic simulations of opening bouncing process.Analytic results indicate that the increase in the stiffness coefficient of contact spring limits the opening bouncing; meanwhile increases in the preload of contact spring and the mass of shaft can enlarge the opening bouncing.

  2. Geometric reduction of dynamical nonlocality in nanoscale quantum circuits

    NARCIS (Netherlands)

    Strambini, E.; Makarenko, K.S.; Abulizi, G.; Jong, de M.P.; Wiel, van der W.G.

    2016-01-01

    Nonlocality is a key feature discriminating quantum and classical physics. Quantum-interference phenomena, such as Young’s double slit experiment, are one of the clearest manifestations of nonlocality, recently addressed as dynamical to specify its origin in the quantum equations of motion. It is we

  3. The time course of activity-regulated cytoskeletal (ARC) gene and protein expression in the whisker-barrel circuit using two paradigms of whisker stimulation.

    Science.gov (United States)

    Khodadad, Aida; Adelson, P David; Lifshitz, Jonathan; Thomas, Theresa Currier

    2015-05-01

    Immediate early genes have previously demonstrated a rapid increase in gene expression after various behavioral paradigms. The main focus of this article is to identify a molecular marker of circuit activation after manual whisker stimulation or exploration of a novel environment. To this end, we investigated the dynamics of ARC transcription in adult male rats during whisker somatosensation throughout the whisker barrel circuit. At various time points, tissue was biopsied from the ventral posterior medial nucleus (VPM) of the thalamus, primary somatosensory barrel field (S1BF) cortex and hippocampus for quantification using real-time PCR and western blot. Our results show that there were no significant differences in ARC gene or protein expression in the VPM after both types of stimulation. However, manual whisker stimulation resulted in increased ARC gene expression at 15, 30, 60 and 300 min in the S1BF, and 15 min in the hippocampus (pwhisker sensation. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. A destabilized bacterial luciferase for dynamic gene expression studies

    Science.gov (United States)

    Allen, Michael S.; Wilgus, John R.; Chewning, Christopher S.; Sayler, Gary S.

    2006-01-01

    Fusions of genetic regulatory elements with reporter genes have long been used as tools for monitoring gene expression and have become a major component in synthetic gene circuit implementation. A major limitation of many of these systems is the relatively long half-life of the reporter protein(s), which prevents monitoring both the initiation and the termination of transcription in real-time. Furthermore, when used as components in synthetic gene circuits, the long time constants associated with reporter protein decay may significantly degrade circuit performance. In this study, short half-life variants of LuxA and LuxB from Photorhabdus luminescens were constructed in Escherichia coli by inclusion of an 11-amino acid carboxy-terminal tag that is recognized by endogenous tail-specific proteases. Results indicated that the addition of the C-terminal tag affected the functional half-life of the holoenzyme when the tag was added to luxA or to both luxA and luxB, but modification of luxB alone did not have a significant effect. In addition, it was also found that alteration of the terminal three amino acid residues of the carboxy-terminal tag fused to LuxA generated variants with half-lives of intermediate length in a manner similar to that reported for GFP. This report is the first instance of the C-terminal tagging approach for the regulation of protein half-life to be applied to an enzyme or monomer of a multi-subunit enzyme complex and will extend the utility of the bacterial luciferase reporter genes for the monitoring of dynamic changes in gene expression. PMID:19003433

  5. Periodic, Quasi-periodic and Chaotic Dynamics in Simple Gene Elements with Time Delays.

    Science.gov (United States)

    Suzuki, Yoko; Lu, Mingyang; Ben-Jacob, Eshel; Onuchic, José N

    2016-02-15

    Regulatory gene circuit motifs play crucial roles in performing and maintaining vital cellular functions. Frequently, theoretical studies of gene circuits focus on steady-state behaviors and do not include time delays. In this study, the inclusion of time delays is shown to entirely change the time-dependent dynamics for even the simplest possible circuits with one and two gene elements with self and cross regulations. These elements can give rise to rich behaviors including periodic, quasi-periodic, weak chaotic, strong chaotic and intermittent dynamics. We introduce a special power-spectrum-based method to characterize and discriminate these dynamical modes quantitatively. Our simulation results suggest that, while a single negative feedback loop of either one- or two-gene element can only have periodic dynamics, the elements with two positive/negative feedback loops are the minimalist elements to have chaotic dynamics. These elements typically have one negative feedback loop that generates oscillations, and another unit that allows frequent switches among multiple steady states or between oscillatory and non-oscillatory dynamics. Possible dynamical features of several simple one- and two-gene elements are presented in details. Discussion is presented for possible roles of the chaotic behavior in the robustness of cellular functions and diseases, for example, in the context of cancer.

  6. Periodic, Quasi-periodic and Chaotic Dynamics in Simple Gene Elements with Time Delays

    Science.gov (United States)

    Suzuki, Yoko; Lu, Mingyang; Ben-Jacob, Eshel; Onuchic, José N.

    2016-02-01

    Regulatory gene circuit motifs play crucial roles in performing and maintaining vital cellular functions. Frequently, theoretical studies of gene circuits focus on steady-state behaviors and do not include time delays. In this study, the inclusion of time delays is shown to entirely change the time-dependent dynamics for even the simplest possible circuits with one and two gene elements with self and cross regulations. These elements can give rise to rich behaviors including periodic, quasi-periodic, weak chaotic, strong chaotic and intermittent dynamics. We introduce a special power-spectrum-based method to characterize and discriminate these dynamical modes quantitatively. Our simulation results suggest that, while a single negative feedback loop of either one- or two-gene element can only have periodic dynamics, the elements with two positive/negative feedback loops are the minimalist elements to have chaotic dynamics. These elements typically have one negative feedback loop that generates oscillations, and another unit that allows frequent switches among multiple steady states or between oscillatory and non-oscillatory dynamics. Possible dynamical features of several simple one- and two-gene elements are presented in details. Discussion is presented for possible roles of the chaotic behavior in the robustness of cellular functions and diseases, for example, in the context of cancer.

  7. A positive feedback-based gene circuit to increase the production of a membrane protein

    Directory of Open Access Journals (Sweden)

    Gennis Robert B

    2010-05-01

    Full Text Available Abstract Background Membrane proteins are an important class of proteins, playing a key role in many biological processes, and are a promising target in pharmaceutical development. However, membrane proteins are often difficult to produce in large quantities for the purpose of crystallographic or biochemical analyses. Results In this paper, we demonstrate that synthetic gene circuits designed specifically to overexpress certain genes can be applied to manipulate the expression kinetics of a model membrane protein, cytochrome bd quinol oxidase in E. coli, resulting in increased expression rates. The synthetic circuit involved is an engineered, autoinducer-independent variant of the lux operon activator LuxR from V. fischeri in an autoregulatory, positive feedback configuration. Conclusions Our proof-of-concept experiments indicate a statistically significant increase in the rate of production of the bd oxidase membrane protein. Synthetic gene networks provide a feasible solution for the problem of membrane protein production.

  8. Quasi-linear vacancy dynamics modeling and circuit analysis of the bipolar memristor.

    Science.gov (United States)

    Abraham, Isaac

    2014-01-01

    The quasi-linear transport equation is investigated for modeling the bipolar memory resistor. The solution accommodates vacancy and circuit level perspectives on memristance. For the first time in literature the component resistors that constitute the contemporary dual variable resistor circuit model are quantified using vacancy parameters and derived from a governing partial differential equation. The model describes known memristor dynamics even as it generates new insight about vacancy migration, bottlenecks to switching speed and elucidates subtle relationships between switching resistance range and device parameters. The model is shown to comply with Chua's generalized equations for the memristor. Independent experimental results are used throughout, to validate the insights obtained from the model. The paper concludes by implementing a memristor-capacitor filter and compares its performance to a reference resistor-capacitor filter to demonstrate that the model is usable for practical circuit analysis.

  9. Incorporating Artificial Neural Networks in the dynamic thermal-hydraulic model of a controlled cryogenic circuit

    Science.gov (United States)

    Carli, S.; Bonifetto, R.; Savoldi, L.; Zanino, R.

    2015-09-01

    A model based on Artificial Neural Networks (ANNs) is developed for the heated line portion of a cryogenic circuit, where supercritical helium (SHe) flows and that also includes a cold circulator, valves, pipes/cryolines and heat exchangers between the main loop and a saturated liquid helium (LHe) bath. The heated line mimics the heat load coming from the superconducting magnets to their cryogenic cooling circuits during the operation of a tokamak fusion reactor. An ANN is trained, using the output from simulations of the circuit performed with the 4C thermal-hydraulic (TH) code, to reproduce the dynamic behavior of the heated line, including for the first time also scenarios where different types of controls act on the circuit. The ANN is then implemented in the 4C circuit model as a new component, which substitutes the original 4C heated line model. For different operational scenarios and control strategies, a good agreement is shown between the simplified ANN model results and the original 4C results, as well as with experimental data from the HELIOS facility confirming the suitability of this new approach which, extended to an entire magnet systems, can lead to real-time control of the cooling loops and fast assessment of control strategies for heat load smoothing to the cryoplant.

  10. Distributed dynamical computation in neural circuits with propagating coherent activity patterns.

    Directory of Open Access Journals (Sweden)

    Pulin Gong

    2009-12-01

    Full Text Available Activity in neural circuits is spatiotemporally organized. Its spatial organization consists of multiple, localized coherent patterns, or patchy clusters. These patterns propagate across the circuits over time. This type of collective behavior has ubiquitously been observed, both in spontaneous activity and evoked responses; its function, however, has remained unclear. We construct a spatially extended, spiking neural circuit that generates emergent spatiotemporal activity patterns, thereby capturing some of the complexities of the patterns observed empirically. We elucidate what kind of fundamental function these patterns can serve by showing how they process information. As self-sustained objects, localized coherent patterns can signal information by propagating across the neural circuit. Computational operations occur when these emergent patterns interact, or collide with each other. The ongoing behaviors of these patterns naturally embody both distributed, parallel computation and cascaded logical operations. Such distributed computations enable the system to work in an inherently flexible and efficient way. Our work leads us to propose that propagating coherent activity patterns are the underlying primitives with which neural circuits carry out distributed dynamical computation.

  11. Neuromorphic log-domain silicon synapse circuits obey bernoulli dynamics: a unifying tutorial analysis.

    Science.gov (United States)

    Papadimitriou, Konstantinos I; Liu, Shih-Chii; Indiveri, Giacomo; Drakakis, Emmanuel M

    2014-01-01

    The field of neuromorphic silicon synapse circuits is revisited and a parsimonious mathematical framework able to describe the dynamics of this class of log-domain circuits in the aggregate and in a systematic manner is proposed. Starting from the Bernoulli Cell Formalism (BCF), originally formulated for the modular synthesis and analysis of externally linear, time-invariant logarithmic filters, and by means of the identification of new types of Bernoulli Cell (BC) operators presented here, a generalized formalism (GBCF) is established. The expanded formalism covers two new possible and practical combinations of a MOS transistor (MOST) and a linear capacitor. The corresponding mathematical relations codifying each case are presented and discussed through the tutorial treatment of three well-known transistor-level examples of log-domain neuromorphic silicon synapses. The proposed mathematical tool unifies past analysis approaches of the same circuits under a common theoretical framework. The speed advantage of the proposed mathematical framework as an analysis tool is also demonstrated by a compelling comparative circuit analysis example of high order, where the GBCF and another well-known log-domain circuit analysis method are used for the determination of the input-output transfer function of the high (4(th)) order topology.

  12. Dynamic wheelset drive load of the railway vehicle caused by short-circuit motor moment

    Directory of Open Access Journals (Sweden)

    Zeman V.

    2009-12-01

    Full Text Available The paper deals with mathematical modelling of dynamic response of the railway vehicle wheelset drives caused by short-circuit traction motor torque. The individual wheelset drive with hollow graduated shaft is one of subsystems of the two-axled vehicle bogie with two wheelset drives. The model respects the viscoelastic suspension of the both engine stators with gear housings mounted on the bogie frame and all the other couplings among bogie drive components. The dynamic response is investigated in dependence on longitudinal creepage and forward velocity of the vehicle at the moment of the sudden short-circuit in one asynchronous traction motor. The method is applied to bogie of the electric locomotive developed for speed about 200 km/h by the company ŠKODA TRANSPORTATION, s. r. o. The wheelset drive vibration is confronted with stability conditions of the whole bogie.

  13. The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops.

    Science.gov (United States)

    Pokhilko, Alexandra; Fernández, Aurora Piñas; Edwards, Kieron D; Southern, Megan M; Halliday, Karen J; Millar, Andrew J

    2012-03-06

    Circadian clocks synchronise biological processes with the day/night cycle, using molecular mechanisms that include interlocked, transcriptional feedback loops. Recent experiments identified the evening complex (EC) as a repressor that can be essential for gene expression rhythms in plants. Integrating the EC components in this role significantly alters our mechanistic, mathematical model of the clock gene circuit. Negative autoregulation of the EC genes constitutes the clock's evening loop, replacing the hypothetical component Y. The EC explains our earlier conjecture that the morning gene Pseudo-Response Regulator 9 was repressed by an evening gene, previously identified with Timing Of CAB Expression1 (TOC1). Our computational analysis suggests that TOC1 is a repressor of the morning genes Late Elongated Hypocotyl and Circadian Clock Associated1 rather than an activator as first conceived. This removes the necessity for the unknown component X (or TOC1mod) from previous clock models. As well as matching timeseries and phase-response data, the model provides a new conceptual framework for the plant clock that includes a three-component repressilator circuit in its complex structure.

  14. A Noise Tolerant and Low Power Dynamic Logic Circuit Using Finfet Technology

    Directory of Open Access Journals (Sweden)

    Sneha Arora

    2015-12-01

    Full Text Available For the improvement of performance and noise tolerance in dynamic logic circuits, a technique is proposed in this paper. A two-input AND gate is designed and simulated in 32nm technology using FinFET device. Simulation results indicate that the proposed technique provides improvement in noise tolerance of about three times and the use of FinFET device reduces the power consumption over the conventional MOSFET designs.

  15. Design and engineering of intracellular-metabolite-sensing/regulation gene circuits in Saccharomyces cerevisiae.

    Science.gov (United States)

    Wang, Meng; Li, Sijin; Zhao, Huimin

    2016-01-01

    The development of high-throughput phenotyping tools is lagging far behind the rapid advances of genotype generation methods. To bridge this gap, we report a new strategy for design, construction, and fine-tuning of intracellular-metabolite-sensing/regulation gene circuits by repurposing bacterial transcription factors and eukaryotic promoters. As proof of concept, we systematically investigated the design and engineering of bacterial repressor-based xylose-sensing/regulation gene circuits in Saccharomyces cerevisiae. We demonstrated that numerous properties, such as induction ratio and dose-response curve, can be fine-tuned at three different nodes, including repressor expression level, operator position, and operator sequence. By applying these gene circuits, we developed a cell sorting based, rapid and robust high-throughput screening method for xylose transporter engineering and obtained a sugar transporter HXT14 mutant with 6.5-fold improvement in xylose transportation capacity. This strategy should be generally applicable and highly useful for evolutionary engineering of proteins, pathways, and genomes in S. cerevisiae.

  16. Neuromorphic control of stepping pattern generation: a dynamic model with analog circuit implementation.

    Science.gov (United States)

    Yang, Zhijun; Cameron, Katherine; Lewinger, William; Webb, Barbara; Murray, Alan

    2012-03-01

    Animals such as stick insects can adaptively walk on complex terrains by dynamically adjusting their stepping motion patterns. Inspired by the coupled Matsuoka and resonate-and-fire neuron models, we present a nonlinear oscillation model as the neuromorphic central pattern generator (CPG) for rhythmic stepping pattern generation. This dynamic model can also be used to actuate the motoneurons on a leg joint with adjustable driving frequencies and duty cycles by changing a few of the model parameters while operating such that different stepping patterns can be generated. A novel mixed-signal integrated circuit design of this dynamic model is subsequently implemented, which, although simplified, shares the equivalent output performance in terms of the adjustable frequency and duty cycle. Three identical CPG models being used to drive three joints can make an arthropod leg of three degrees of freedom. With appropriate initial circuit parameter settings, and thus suitable phase lags among joints, the leg is expected to walk on a complex terrain with adaptive steps. The adaptation is associated with the circuit parameters mediated both by the higher level nervous system and the lower level sensory signals. The model is realized using a 0.3- complementary metal-oxide-semiconductor process and the results are reported.

  17. Tunable 13C/1H dual channel matching circuit for dynamic nuclear polarization system with cross-polarization

    DEFF Research Database (Denmark)

    Rybalko, Oleksandr; Bowen, Sean; Zhurbenko, Vitaliy

    2016-01-01

    In this paper we report initial results of design and practical implementation of tuning and matching circuit to estimate a performance of Dynamic Nuclear Polarization (DNP) at a magnetic field of 6.7 T. It is shown that developed circuit for signal observation is compact, easy to make and provides...

  18. Pulsewidth modulated DC-to-DC power conversion circuits, dynamics, and control designs

    CERN Document Server

    Choi, Byungcho

    2013-01-01

    This is the definitive reference for anyone involved in pulsewidth modulated DC-to-DC power conversion Pulsewidth Modulated DC-to-DC Power Conversion: Circuits, Dynamics, and Control Designs provides engineers, researchers, and students in the power electronics field with comprehensive and complete guidance to understanding pulsewidth modulated (PWM) DC-to-DC power converters. Presented in three parts, the book addresses the circuitry and operation of PWM DC-to-DC converters and their dynamic characteristics, along with in-depth discussions of control design of PWM DC-to

  19. Design to conditioning circuits of dynamic compensation of reactive power in the intelligence voltage controller

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    <正>The paper introduces one design idea that making use of SCM to control Real-timely the dynamic compensation of reactive power.Firstly,design one Circuit to Sample the voltage and current,and by these datas we can easily calculate the power factor,and Voltage controller in the microcontroller to determine whether input the compensation capacitance according to the size of power factor,the paper also analyzes the principle of capacitance compensation and calculation method. Dynamic compensation for the entire process is quick and accurate.

  20. Optogenetic dissection of neuronal circuits in zebrafish using viral gene transfer and the Tet system

    Directory of Open Access Journals (Sweden)

    Peixin Zhu

    2009-12-01

    Full Text Available The conditional expression of transgenes at high levels in sparse and specific populations of neurons is important for high-resolution optogenetic analyses of neuronal circuits. We explored two complementary methods, viral gene delivery and the iTet-Off system, to express transgenes in the brain of zebrafish. High-level gene expression in neurons was achieved by Sindbis and Rabies viruses. The Tet system produced strong and specific gene expression that could be modulated conveniently by doxycycline. Moreover, transgenic lines showed expression in distinct, sparse and stable populations of neurons that appeared to be subsets of the neurons targeted by the promoter driving the Tet activator. The Tet system therefore provides the opportunity to generate libraries of diverse expression patterns similar to gene trap approaches or the thy-1 promoter in mice, but with the additional possibility to pre-select cell types of interest. In transgenic lines expressing channelrhodopsin-2, action potential firing could be precisely controlled by two-photon stimulation at low laser power, presumably because the expression levels of the Tet-controlled genes were high even in adults. In channelrhodopsin-2-expressing larvae, optical stimulation with a single blue LED evoked distinct swimming behaviors including backward swimming. These approaches provide new opportunities for the optogenetic dissection of neuronal circuit structure and function.

  1. Sequential logic model deciphers dynamic transcriptional control of gene expressions.

    Directory of Open Access Journals (Sweden)

    Zhen Xuan Yeo

    Full Text Available BACKGROUND: Cellular signaling involves a sequence of events from ligand binding to membrane receptors through transcription factors activation and the induction of mRNA expression. The transcriptional-regulatory system plays a pivotal role in the control of gene expression. A novel computational approach to the study of gene regulation circuits is presented here. METHODOLOGY: Based on the concept of finite state machine, which provides a discrete view of gene regulation, a novel sequential logic model (SLM is developed to decipher control mechanisms of dynamic transcriptional regulation of gene expressions. The SLM technique is also used to systematically analyze the dynamic function of transcriptional inputs, the dependency and cooperativity, such as synergy effect, among the binding sites with respect to when, how much and how fast the gene of interest is expressed. PRINCIPAL FINDINGS: SLM is verified by a set of well studied expression data on endo16 of Strongylocentrotus purpuratus (sea urchin during the embryonic midgut development. A dynamic regulatory mechanism for endo16 expression controlled by three binding sites, UI, R and Otx is identified and demonstrated to be consistent with experimental findings. Furthermore, we show that during transition from specification to differentiation in wild type endo16 expression profile, SLM reveals three binary activities are not sufficient to explain the transcriptional regulation of endo16 expression and additional activities of binding sites are required. Further analyses suggest detailed mechanism of R switch activity where indirect dependency occurs in between UI activity and R switch during specification to differentiation stage. CONCLUSIONS/SIGNIFICANCE: The sequential logic formalism allows for a simplification of regulation network dynamics going from a continuous to a discrete representation of gene activation in time. In effect our SLM is non-parametric and model-independent, yet

  2. Fault Diagnosis for Compensating Capacitors of Jointless Track Circuit Based on Dynamic Time Warping

    Directory of Open Access Journals (Sweden)

    Wei Dong

    2014-01-01

    Full Text Available Aiming at the problem of online fault diagnosis for compensating capacitors of jointless track circuit, a dynamic time warping (DTW based diagnosis method is proposed in this paper. Different from the existing related works, this method only uses the ground indoor monitoring signals of track circuit to locate the faulty compensating capacitor, not depending on the shunt current of inspection train, which is an indispensable condition for existing methods. So, it can be used for online diagnosis of compensating capacitor, which has not yet been realized by existing methods. To overcome the key problem that track circuit cannot obtain the precise position of the train, the DTW method is used for the first time in this situation to recover the function relationship between receiver’s peak voltage and shunt position. The necessity, thinking, and procedure of the method are described in detail. Besides the classical DTW based method, two improved methods for improving classification quality and reducing computation complexity are proposed. Finally, the diagnosis experiments based on the simulation model of track circuit show the effectiveness of the proposed methods.

  3. Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders.

    Science.gov (United States)

    Sahin, Mustafa; Sur, Mriganka

    2015-11-20

    Research in the genetics of neurodevelopmental disorders such as autism suggests that several hundred genes are likely risk factors for these disorders. This heterogeneity presents a challenge and an opportunity at the same time. Although the exact identity of many of the genes remains to be discovered, genes identified to date encode proteins that play roles in certain conserved pathways: protein synthesis, transcriptional and epigenetic regulation, and synaptic signaling. The next generation of research in neurodevelopmental disorders must address the neural circuitry underlying the behavioral symptoms and comorbidities, the cell types playing critical roles in these circuits, and common intercellular signaling pathways that link diverse genes. Results from clinical trials have been mixed so far. Only when we can leverage the heterogeneity of neurodevelopmental disorders into precision medicine will the mechanism-based therapeutics for these disorders start to unlock success.

  4. Nucleosome repositioning underlies dynamic gene expression.

    Science.gov (United States)

    Nocetti, Nicolas; Whitehouse, Iestyn

    2016-03-15

    Nucleosome repositioning at gene promoters is a fundamental aspect of the regulation of gene expression. However, the extent to which nucleosome repositioning is used within eukaryotic genomes is poorly understood. Here we report a comprehensive analysis of nucleosome positions as budding yeast transit through an ultradian cycle in which expression of >50% of all genes is highly synchronized. We present evidence of extensive nucleosome repositioning at thousands of gene promoters as genes are activated and repressed. During activation, nucleosomes are relocated to allow sites of general transcription factor binding and transcription initiation to become accessible. The extent of nucleosome shifting is closely related to the dynamic range of gene transcription and generally related to DNA sequence properties and use of the coactivators TFIID or SAGA. However, dynamic gene expression is not limited to SAGA-regulated promoters and is an inherent feature of most genes. While nucleosome repositioning occurs pervasively, we found that a class of genes required for growth experience acute nucleosome shifting as cells enter the cell cycle. Significantly, our data identify that the ATP-dependent chromatin-remodeling enzyme Snf2 plays a fundamental role in nucleosome repositioning and the expression of growth genes. We also reveal that nucleosome organization changes extensively in concert with phases of the cell cycle, with large, regularly spaced nucleosome arrays being established in mitosis. Collectively, our data and analysis provide a framework for understanding nucleosome dynamics in relation to fundamental DNA-dependent transactions.

  5. Feeding state, insulin and NPR-1 modulate chemoreceptor gene expression via integration of sensory and circuit inputs.

    Directory of Open Access Journals (Sweden)

    Matthew Gruner

    2014-10-01

    Full Text Available Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK-dependent chemoreceptor, srh-234, in C. elegans whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of srh-234 is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2 and DAF-16 (FOXO transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions.

  6. Non-linear classical dynamics in a superconducting circuit containing a cavity and a Josephson junction

    Energy Technology Data Exchange (ETDEWEB)

    Meister, Selina; Kubala, Bjoern; Gramich, Vera; Mecklenburg, Michael; Stockburger, Juergen T.; Ankerhold, Joachim [Institute for Complex Quantum Systems, Ulm University, Albert-Einstein-Allee 11, 89069 Ulm (Germany)

    2015-07-01

    Motivated by recent experiments a superconducting hybrid circuit consisting of a voltage biased Josephson junction in series with a resonator is studied. For strong driving the dynamics of the system can be very complex, even in the classical regime. Studying the dissipative dynamics within a Langevin-type description, we obtain well-defined dynamical steady states. In contrast to the well-known case of anharmonic potentials, like the Duffing or parametric oscillator, in our case the non-linearity stems from the peculiar way the external drive couples to the system [2]. We investigate the resonance behaviour of this non-linear hybrid system, in particular when driving at higher- or subharmonics. The resulting down- and up-conversions can be observed both, as resonances in the I-V curve, and in the emitted microwave radiation, which yields additional spectral information.

  7. A Memristor-Based Hyperchaotic System with Hidden Attractors: Dynamics, Synchronization and Circuital Emulating

    Directory of Open Access Journals (Sweden)

    V.-T. Pham

    2014-11-01

    Full Text Available Memristor-based systems and their potential applications, in which memristor is both a nonlinear element and a memory element, have been received significant attention recently. A memristor-based hyperchaotic system with hidden attractor is studied in this paper. The dynamics properties of this hyperchaotic system are discovered through equilibria, Lyapunov exponents, bifurcation diagram, Poincaré map and limit cycles. In addition, its anti-synchronization scheme via adaptive control method is also designed and MATLAB simulations are shown. Finally, an electronic circuit emulating the memristor-based hyperchaotic system has been designed using off-the-shelf components.

  8. Dynamic spike threshold and nonlinear dendritic computation for coincidence detection in neuromorphic circuits.

    Science.gov (United States)

    Hsu, Chih-Chieh; Parker, Alice C

    2014-01-01

    We present an electronic cortical neuron incorporating dynamic spike threshold and active dendritic properties. The circuit is simulated using a carbon nanotube field-effect transistor SPICE model. We demonstrate that our neuron has lower spike threshold for coincident synaptic inputs; however when the synaptic inputs are not in synchrony, it requires larger depolarization to evoke the neuron to fire. We also demonstrate that a dendritic spike is key to precisely-timed input-output transformation, produces reliable firing and results in more resilience to input jitter within an individual neuron.

  9. Comparison of stationary and oscillatory dynamics described by differential equations and Boolean maps in transcriptional regulatory circuits

    Energy Technology Data Exchange (ETDEWEB)

    Ye Weiming [Department of Physics, Beijing Normal University, Beijing 100875 (China); Beijing-Hong Kong-Singapore Joint Center of Nonlinear and Complex Systems, Beijing Normal University Branch, Beijing (China); Li Pengfei; Huang Xuhui; Xia Qinzhi; Mi Yuanyuan [Department of Physics, Beijing Normal University, Beijing 100875 (China); Chen Runsheng, E-mail: crs@sun5.ibp.ac.c [Bioinformatics Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Hu Gang, E-mail: ganghu@bnu.edu.c [Department of Physics, Beijing Normal University, Beijing 100875 (China); Beijing-Hong Kong-Singapore Joint Center of Nonlinear and Complex Systems, Beijing Normal University Branch, Beijing (China)

    2010-10-25

    Exploring the principle and relationship of gene transcriptional regulations (TR) has been becoming a generally researched issue. So far, two major mathematical methods, ordinary differential equation (ODE) method and Boolean map (BM) method have been widely used for these purposes. It is commonly believed that simplified BMs are reasonable approximations of more realistic ODEs, and both methods may reveal qualitatively the same essential features though the dynamical details of both systems may show some differences. In this Letter we exhaustively enumerated all the 3-gene networks and many autonomous randomly constructed TR networks with more genes by using both the ODE and BM methods. In comparison we found that both methods provide practically identical results in most of cases of steady solutions. However, to our great surprise, most of network structures showing periodic cycles with the BM method possess only stationary states in ODE descriptions. These observations strongly suggest that many periodic oscillations and other complicated oscillatory states revealed by the BM rule may be related to the computational errors of variable and time discretizations and rarely have correspondence in realistic biology transcriptional regulatory circuits.

  10. Circuit topology of self-interacting chains: implications for folding and unfolding dynamics.

    Science.gov (United States)

    Mugler, Andrew; Tans, Sander J; Mashaghi, Alireza

    2014-11-07

    Understanding the relationship between molecular structure and folding is a central problem in disciplines ranging from biology to polymer physics and DNA origami. Topology can be a powerful tool to address this question. For a folded linear chain, the arrangement of intra-chain contacts is a topological property because rearranging the contacts requires discontinuous deformations. Conversely, the topology is preserved when continuously stretching the chain while maintaining the contact arrangement. Here we investigate how the folding and unfolding of linear chains with binary contacts is guided by the topology of contact arrangements. We formalize the topology by describing the relations between any two contacts in the structure, which for a linear chain can either be in parallel, in series, or crossing each other. We show that even when other determinants of folding rate such as contact order and size are kept constant, this 'circuit' topology determines folding kinetics. In particular, we find that the folding rate increases with the fractions of parallel and crossed relations. Moreover, we show how circuit topology constrains the conformational phase space explored during folding and unfolding: the number of forbidden unfolding transitions is found to increase with the fraction of parallel relations and to decrease with the fraction of series relations. Finally, we find that circuit topology influences whether distinct intermediate states are present, with crossed contacts being the key factor. The approach presented here can be more generally applied to questions on molecular dynamics, evolutionary biology, molecular engineering, and single-molecule biophysics.

  11. Sub-circuits of a gene regulatory network control a developmental epithelial-mesenchymal transition.

    Science.gov (United States)

    Saunders, Lindsay R; McClay, David R

    2014-04-01

    Epithelial-mesenchymal transition (EMT) is a fundamental cell state change that transforms epithelial to mesenchymal cells during embryonic development, adult tissue repair and cancer metastasis. EMT includes a complex series of intermediate cell state changes including remodeling of the basement membrane, apical constriction, epithelial de-adhesion, directed motility, loss of apical-basal polarity, and acquisition of mesenchymal adhesion and polarity. Transcriptional regulatory state changes must ultimately coordinate the timing and execution of these cell biological processes. A well-characterized gene regulatory network (GRN) in the sea urchin embryo was used to identify the transcription factors that control five distinct cell changes during EMT. Single transcription factors were perturbed and the consequences followed with in vivo time-lapse imaging or immunostaining assays. The data show that five different sub-circuits of the GRN control five distinct cell biological activities, each part of the complex EMT process. Thirteen transcription factors (TFs) expressed specifically in pre-EMT cells were required for EMT. Three TFs highest in the GRN specified and activated EMT (alx1, ets1, tbr) and the 10 TFs downstream of those (tel, erg, hex, tgif, snail, twist, foxn2/3, dri, foxb, foxo) were also required for EMT. No single TF functioned in all five sub-circuits, indicating that there is no EMT master regulator. Instead, the resulting sub-circuit topologies suggest EMT requires multiple simultaneous regulatory mechanisms: forward cascades, parallel inputs and positive-feedback lock downs. The interconnected and overlapping nature of the sub-circuits provides one explanation for the seamless orchestration by the embryo of cell state changes leading to successful EMT.

  12. Rational design of modular circuits for gene transcription: A test of the bottom-up approach

    Directory of Open Access Journals (Sweden)

    Giordano Emanuele

    2010-11-01

    Full Text Available Abstract Background Most of synthetic circuits developed so far have been designed by an ad hoc approach, using a small number of components (i.e. LacI, TetR and a trial and error strategy. We are at the point where an increasing number of modular, inter-changeable and well-characterized components is needed to expand the construction of synthetic devices and to allow a rational approach to the design. Results We used interchangeable modular biological parts to create a set of novel synthetic devices for controlling gene transcription, and we developed a mathematical model of the modular circuits. Model parameters were identified by experimental measurements from a subset of modular combinations. The model revealed an unexpected feature of the lactose repressor system, i.e. a residual binding affinity for the operator site by induced lactose repressor molecules. Once this residual affinity was taken into account, the model properly reproduced the experimental data from the training set. The parameters identified in the training set allowed the prediction of the behavior of networks not included in the identification procedure. Conclusions This study provides new quantitative evidences that the use of independent and well-characterized biological parts and mathematical modeling, what is called a bottom-up approach to the construction of gene networks, can allow the design of new and different devices re-using the same modular parts.

  13. A Large-Scale Circuit Mechanism for Hierarchical Dynamical Processing in the Primate Cortex.

    Science.gov (United States)

    Chaudhuri, Rishidev; Knoblauch, Kenneth; Gariel, Marie-Alice; Kennedy, Henry; Wang, Xiao-Jing

    2015-10-21

    We developed a large-scale dynamical model of the macaque neocortex, which is based on recently acquired directed- and weighted-connectivity data from tract-tracing experiments, and which incorporates heterogeneity across areas. A hierarchy of timescales naturally emerges from this system: sensory areas show brief, transient responses to input (appropriate for sensory processing), whereas association areas integrate inputs over time and exhibit persistent activity (suitable for decision-making and working memory). The model displays multiple temporal hierarchies, as evidenced by contrasting responses to visual versus somatosensory stimulation. Moreover, slower prefrontal and temporal areas have a disproportionate impact on global brain dynamics. These findings establish a circuit mechanism for "temporal receptive windows" that are progressively enlarged along the cortical hierarchy, suggest an extension of time integration in decision making from local to large circuits, and should prompt a re-evaluation of the analysis of functional connectivity (measured by fMRI or electroencephalography/magnetoencephalography) by taking into account inter-areal heterogeneity.

  14. Simple mathematical models of gene regulatory dynamics

    CERN Document Server

    Mackey, Michael C; Tyran-Kamińska, Marta; Zeron, Eduardo S

    2016-01-01

    This is a short and self-contained introduction to the field of mathematical modeling of gene-networks in bacteria. As an entry point to the field, we focus on the analysis of simple gene-network dynamics. The notes commence with an introduction to the deterministic modeling of gene-networks, with extensive reference to applicable results coming from dynamical systems theory. The second part of the notes treats extensively several approaches to the study of gene-network dynamics in the presence of noise—either arising from low numbers of molecules involved, or due to noise external to the regulatory process. The third and final part of the notes gives a detailed treatment of three well studied and concrete examples of gene-network dynamics by considering the lactose operon, the tryptophan operon, and the lysis-lysogeny switch. The notes contain an index for easy location of particular topics as well as an extensive bibliography of the current literature. The target audience of these notes are mainly graduat...

  15. Dynamics of bacterial gene regulation

    Science.gov (United States)

    Narang, Atul

    2009-03-01

    The phenomenon of diauxic growth is a classical problem of bacterial gene regulation. The most well studied example of this phenomenon is the glucose-lactose diauxie, which occurs because the expression of the lac operon is strongly repressed in the presence of glucose. This repression is often explained by appealing to molecular mechanisms such as cAMP activation and inducer exclusion. I will begin by analyzing data showing that these molecular mechanisms cannot explain the strong lac repression because they exert a relatively weak effect. I will then present a minimal model accounting only for enzyme induction and dilution, which yields strong repression despite the absence of catabolite repression and inducer exclusion. The model also explains the growth patterns observed in batch and continuous cultures of various bacterial strains and substrate mixtures. The talk will conclude with a discussion of the experimental evidence regarding positive feedback, the key component of the minimal model.

  16. Changes in maternal gene expression in olfactory circuits in the immediate postpartum period.

    Directory of Open Access Journals (Sweden)

    Sofija V Canavan

    2011-07-01

    Full Text Available Regulation of maternal behavior in the immediate postpartum period involves neural circuits in reward and homeostasis systems responding to cues from the newborn. Our aim was to assess one specific regulatory mechanism: the role that olfaction plays in the onset and modulation of parenting behavior. We focused on changes in gene expression in olfactory brain regions, examining nine genes found in previous knockout studies to be necessary for maternal behavior. Using a qPCR-based approach, we assessed changes in gene expression in response to exposure to pups in eleven microdissected olfactory brain regions. Over the first postpartum days, all nine genes were detected in all eleven regions (at differing levels and their expression changed in response to pup exposure. As a general trend, five genes (Dbh, Esr1, FosB, Foxb1 and Oxtr were found to decrease their expression in most of the olfactory regions examined, while two genes (Mest and Prlr were found to increase expression. Nos1 and Peg3 levels remained relatively stable except in the accessory olfactory bulb (AOB, where greater than 4 fold increases in expression were observed. The largest magnitude expression changes in this study were found in the AOB, which mediates a variety of olfactory cues that elicit stereotypic behaviors such as mating and aggression as well as some non-pheromone odors. Previous analyses of null mice for the nine genes assessed here have rarely examined olfactory function. Our data suggest that there may be olfactory effects in these null mice which contribute to the observed maternal behavioral phenotypes. Collectively, these data support the hypothesis that olfactory processing is an important sensory regulator of maternal behavior.

  17. Visualizing changes in circuit activity resulting from denervation and reinnervation using immediate early gene expression.

    Science.gov (United States)

    Temple, Meredith D; Worley, Paul F; Steward, Oswald

    2003-04-01

    We describe a novel strategy to evaluate circuit function after brain injury that takes advantage of experience-dependent immediate early gene (IEG) expression. When normal rats undergo training or are exposed to a novel environment, there is a strong induction of IEG expression in forebrain regions, including the hippocampus. This gene induction identifies the neurons that are engaged during the experience. Here, we demonstrate that experience-dependent IEG induction is diminished after brain injury in young adult rats (120-200 gm), specifically after unilateral lesions of the entorhinal cortex (EC), and then recovers with a time course consistent with reinnervation. In situ hybridization techniques were used to assess the expression of the activity-regulated cytoskeleton-associated protein Arc at various times after the lesion (4, 8, 12, 16, or 30 d). One group of rats was allowed to explore a complex novel environment for 1 hr; control operated animals remained in their home cage. In unoperated animals, exposure to the novel environment induced Arc mRNA levels in most pyramidal neurons in CA1, in many pyramidal neurons in CA3, and in a small number of dentate granule cells. This characteristic pattern of induction was absent at early time points after unilateral EC lesions (4 and 8 d) but recovered progressively at later time points. The recovery of Arc expression occurred with approximately the same time course as the reinnervation of the dentate gyrus as a result of postlesion sprouting. These results document a novel approach for quantitatively assessing activity-regulated gene expression in polysynaptic circuits after trauma.

  18. Development of a computer code for dynamic analysis of the primary circuit of advanced reactors

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Jussie Soares da; Lira, Carlos A.B.O.; Magalhaes, Mardson A. de Sa, E-mail: cabol@ufpe.b [Universidade Federal de Pernambuco (DEN/UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear

    2011-07-01

    Currently, advanced reactors are being developed, seeking for enhanced safety, better performance and low environmental impacts. Reactor designs must follow several steps and numerous tests before a conceptual project could be certified. In this sense, computational tools become indispensable in the preparation of such projects. Thus, this study aimed at the development of a computational tool for thermal-hydraulic analysis by coupling two computer codes to evaluate the influence of transients caused by pressure variations and flow surges in the region of the primary circuit of IRIS reactor between the core and the pressurizer. For the simulation, it was used a situation of 'insurge', characterized by the entry of water in the pressurizer, due to the expansion of the refrigerant in the primary circuit. This expansion was represented by a pressure disturbance in step form, through the block 'step' of SIMULINK, thus enabling the transient startup. The results showed that the dynamic tool, obtained through the coupling of the codes, generated very satisfactory responses within model limitations, preserving the most important phenomena in the process. (author)

  19. Dynamic changes in neural circuit topology following mild mechanical injury in vitro.

    Science.gov (United States)

    Patel, Tapan P; Ventre, Scott C; Meaney, David F

    2012-01-01

    Despite its enormous incidence, mild traumatic brain injury is not well understood. One aspect that needs more definition is how the mechanical energy during injury affects neural circuit function. Recent developments in cellular imaging probes provide an opportunity to assess the dynamic state of neural networks with single-cell resolution. In this article, we developed imaging methods to assess the state of dissociated cortical networks exposed to mild injury. We estimated the imaging conditions needed to achieve accurate measures of network properties, and applied these methodologies to evaluate if mild mechanical injury to cortical neurons produces graded changes to either spontaneous network activity or altered network topology. We found that modest injury produced a transient increase in calcium activity that dissipated within 1 h after injury. Alternatively, moderate mechanical injury produced immediate disruption in network synchrony, loss in excitatory tone, and increased modular topology. A calcium-activated neutral protease (calpain) was a key intermediary in these changes; blocking calpain activation restored the network nearly completely to its pre-injury state. Together, these findings show a more complex change in neural circuit behavior than previously reported for mild mechanical injury, and highlight at least one important early mechanism responsible for these changes.

  20. Ultralow-power GaAs MESFET MSI circuits using two-phase dynamic FET logic

    DEFF Research Database (Denmark)

    Lassen, Peter Stuhr; Long, S. I.; Nary, K. R.

    1993-01-01

    Two-phase dynamic FET logic (TDFL) gates are used in GaAs MESFET MSI circuits to implement very low power 4-b ripple carry adders and a variable modulus (2 to 31) prescaler. Operation of the adders is demonstrated at 500 MHz with an associated power dissipation of less than 1.0 mW and at 750 MHz...... with Pd=1.7 mW. The prescaler, which contains 166 TDFL gates and 79 static gates, is shown to operate up to 850 MHz with an associated power dissipation of 9.2 mW from its 1.0-V supply. The operation of the adders and prescalers demonstrates the use of three- and four-input TDFL gates and a completely...

  1. New signatures of the dynamical Casimir effect in a superconducting circuit

    CERN Document Server

    Rego, Andreson L C; Alves, Danilo T; Farina, C

    2014-01-01

    We found new signatures of the dynamical Casimir effect (DCE) in the context of superconducting circuits. We show that if the recent experiment made by Wilson {\\it et al}, which brought the DCE into reality for the first time, is repeated with slight modifications (for instance, different values for the capacitance of the SQUID), three remarkable results will show up, namely: {\\it (i)} a quite different spectral distribution for the created particles, deviating from the typical parabolic shape; {\\it (ii)} an enhancement by a factor of approximately $5 \\times 10^3 $ in the number of created particles with half driven frequency of the effective moving mirror and {\\it (iii)} an enhancement by a factor of $3 \\times 10^2$ in the particle creation rate. These results may guide the experimentalists in their search for alternative routes to observe the DCE in future experiments.

  2. Refined anatomical isolation of functional sleep circuits exhibits distinctive regional and circadian gene transcriptional profiles.

    Science.gov (United States)

    Winrow, Christopher J; Tanis, Keith Q; Rigby, Alison M; Taylor, Rhonda R; Serikawa, Kyle; McWhorter, Mollie; Tokiwa, George Y; Marton, Matthew J; Stone, David J; Koblan, Kenneth S; Renger, John J

    2009-05-19

    Powerful new approaches to study molecular variation in distinct neuronal populations have recently been developed enabling a more precise investigation of the control of neural circuits involved in complex behaviors such as wake and sleep. We applied laser capture microdissection (LCM) to isolate precise brain nuclei from rat CNS at opposing circadian time points associated with wake and sleep. Discrete anatomical and temporal analysis was performed to examine the extent of variation in the transcriptional control associated with both identifiable anatomical nuclei and with light/dark cycle. Precise isolation of specific brain nuclei regulating sleep and arousal, including the LC, SCN, TMN, VTA, and VLPO, demonstrated robust changes in gene expression. Many of these differences were not observed in previous studies where whole brain lysates or gross dissections were used to probe for changes in gene expression. The robust and differential profiles of genomic data obtained from the approaches used herein underscore the requirement for careful anatomical refinement in CNS gene expression studies designed to understand genomic control within behaviorally-linked, but functionally isolated brain nuclei.

  3. Parameter estimation and determinability analysis applied to Drosophila gap gene circuits

    Directory of Open Access Journals (Sweden)

    Jaeger Johannes

    2008-09-01

    Full Text Available Abstract Background Mathematical modeling of real-life processes often requires the estimation of unknown parameters. Once the parameters are found by means of optimization, it is important to assess the quality of the parameter estimates, especially if parameter values are used to draw biological conclusions from the model. Results In this paper we describe how the quality of parameter estimates can be analyzed. We apply our methodology to assess parameter determinability for gene circuit models of the gap gene network in early Drosophila embryos. Conclusion Our analysis shows that none of the parameters of the considered model can be determined individually with reasonable accuracy due to correlations between parameters. Therefore, the model cannot be used as a tool to infer quantitative regulatory weights. On the other hand, our results show that it is still possible to draw reliable qualitative conclusions on the regulatory topology of the gene network. Moreover, it improves previous analyses of the same model by allowing us to identify those interactions for which qualitative conclusions are reliable, and those for which they are ambiguous.

  4. Dynamic SVL and body bias for low leakage power and high performance in CMOS digital circuits

    Science.gov (United States)

    Deshmukh, Jyoti; Khare, Kavita

    2012-12-01

    In this article, a new complementary metal oxide semiconductor design scheme called dynamic self-controllable voltage level (DSVL) is proposed. In the proposed scheme, leakage power is controlled by dynamically disconnecting supply to inactive blocks and adjusting body bias to further limit leakage and to maintain performance. Leakage power measurements at 1.8 V, 75°C demonstrate power reduction by 59.4% in case of 1 bit full adder and by 43.0% in case of a chain of four inverters using SVL circuit as a power switch. Furthermore, we achieve leakage power reduction by 94.7% in case of 1 bit full adder and by 91.8% in case of a chain of four inverters using dynamic body bias. The forward body bias of 0.45 V applied in active mode improves the maximum operating frequency by 16% in case of 1 bit full adder and 5.55% in case of a chain of inverters. Analysis shows that additional benefits of using the DSVL and body bias include high performance, low leakage power consumption in sleep mode, single threshold implementation and state retention even in standby mode.

  5. Dynamical Analysis and Circuit Simulation of a New Fractional-Order Hyperchaotic System and Its Discretization

    Science.gov (United States)

    El-Sayed, A. M. A.; Elsonbaty, A.; Elsadany, A. A.; Matouk, A. E.

    2016-12-01

    This paper presents an analytical framework to investigate the dynamical behavior of a new fractional-order hyperchaotic circuit system. A sufficient condition for existence, uniqueness and continuous dependence on initial conditions of the solution of the proposed system is derived. The local stability of all the system’s equilibrium points are discussed using fractional Routh-Hurwitz test. Then the analytical conditions for the existence of a pitchfork bifurcation in this system with fractional-order parameter less than 1/3 are provided. Conditions for the existence of Hopf bifurcation in this system are also investigated. The dynamics of discretized form of our fractional-order hyperchaotic system are explored. Chaos control is also achieved in discretized system using delay feedback control technique. The numerical simulation are presented to confirm our theoretical analysis via phase portraits, bifurcation diagrams and Lyapunov exponents. A text encryption algorithm is presented based on the proposed fractional-order system. The results show that the new system exhibits a rich variety of dynamical behaviors such as limit cycles, chaos and transient phenomena where fractional-order derivative represents a key parameter in determining system qualitative behavior.

  6. Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics.

    Directory of Open Access Journals (Sweden)

    Tsvia Gildor

    2015-07-01

    Full Text Available Accurate temporal control of gene expression is essential for normal development and must be robust to natural genetic and environmental variation. Studying gene expression variation within and between related species can delineate the level of expression variability that development can tolerate. Here we exploit the comprehensive model of sea urchin gene regulatory networks and generate high-density expression profiles of key regulatory genes of the Mediterranean sea urchin, Paracentrotus lividus (Pl. The high resolution of our studies reveals highly reproducible gene initiation times that have lower variation than those of maximal mRNA levels between different individuals of the same species. This observation supports a threshold behavior of gene activation that is less sensitive to input concentrations. We then compare Mediterranean sea urchin gene expression profiles to those of its Pacific Ocean relative, Strongylocentrotus purpuratus (Sp. These species shared a common ancestor about 40 million years ago and show highly similar embryonic morphologies. Our comparative analyses of five regulatory circuits operating in different embryonic territories reveal a high conservation of the temporal order of gene activation but also some cases of divergence. A linear ratio of 1.3-fold between gene initiation times in Pl and Sp is partially explained by scaling of the developmental rates with temperature. Scaling the developmental rates according to the estimated Sp-Pl ratio and normalizing the expression levels reveals a striking conservation of relative dynamics of gene expression between the species. Overall, our findings demonstrate the ability of biological developmental systems to tightly control the timing of gene activation and relative dynamics and overcome expression noise induced by genetic variation and growth conditions.

  7. The study of hybrid model identification,computation analysis and fault location for nonlinear dynamic circuits and systems

    Institute of Scientific and Technical Information of China (English)

    XIE Hong; HE Yi-gang; ZENG Guan-da

    2006-01-01

    This paper presents the hybrid model identification for a class of nonlinear circuits and systems via a combination of the block-pulse function transform with the Volterra series.After discussing the method to establish the hybrid model and introducing the hybrid model identification,a set of relative formulas are derived for calculating the hybrid model and computing the Volterra series solution of nonlinear dynamic circuits and systems.In order to significantly reduce the computation cost for fault location,the paper presents a new fault diagnosis method based on multiple preset models that can be realized online.An example of identification simulation and fault diagnosis are given.Results show that the method has high accuracy and efficiency for fault location of nonlinear dynamic circuits and systems.

  8. Circuits for Processing Dynamic Interaural Intensity Disparities in the Inferior Colliculus

    Science.gov (United States)

    Pollak, George D.

    2013-01-01

    Interaural intensity disparities (IIDs), the cues all animals use to localize high frequency sounds, are initially processed in the lateral superior olive (LSO) by a subtractive process where inputs from one ear excite and inputs from the other ear inhibit LSO neurons. Such cells are called excitatory-inhibitory (EI) neurons and are prominent not only in the LSO but also in higher nuclei, which include the dorsal nucleus of the lateral lemniscus (DNLL) and inferior colliculus (IC). The IC is of particular interest since its EI cells receive diverse innervation patterns from a large number of lower nuclei, which include the DNLLs and LSOs, and thus comprise a population with diverse binaural properties. The first part of this review focuses on the circuits that create EI cells in the LSO, DNLL and IC. The second section then turns to the responses evoked by dynamic IIDs that change over time, as with multiple sounds that emanate from different regions of space or moving sound sources. I show that many EI neurons in the IC respond to dynamic IIDs in ways that are not predictable from their responses to static IIDs, IIDs presented one at a time. In the final section, results from in vivo whole cell recording in the IC are presented and address the connectional basis for the responsiveness to dynamic IIDs. The principal conclusion is that EI cells comprise a diverse population. The diversity is created by the particular set of inputs each EI type receives and is expressed in the differences in the responses to dynamic IIDs that are generated by those inputs. These results show that the construction of EI neurons in the IC imparts features that not only encode the location of an individual sound source, but also that allow animals to determine the direction of a moving sound and to focus and localize a single sound in midst of many sounds, as typically occurs in the daily lives of all animals. PMID:22343068

  9. A general model for binary cell fate decision gene circuits with degeneracy: indeterminacy and switch behavior in the absence of cooperativity.

    Directory of Open Access Journals (Sweden)

    Mircea Andrecut

    Full Text Available BACKGROUND: The gene regulatory circuit motif in which two opposing fate-determining transcription factors inhibit each other but activate themselves has been used in mathematical models of binary cell fate decisions in multipotent stem or progenitor cells. This simple circuit can generate multistability and explains the symmetric "poised" precursor state in which both factors are present in the cell at equal amounts as well as the resolution of this indeterminate state as the cell commits to either cell fate characterized by an asymmetric expression pattern of the two factors. This establishes the two alternative stable attractors that represent the two fate options. It has been debated whether cooperativity of molecular interactions is necessary to produce such multistability. PRINCIPAL FINDINGS: Here we take a general modeling approach and argue that this question is not relevant. We show that non-linearity can arise in two distinct models in which no explicit interaction between the two factors is assumed and that distinct chemical reaction kinetic formalisms can lead to the same (generic dynamical system form. Moreover, we describe a novel type of bifurcation that produces a degenerate steady state that can explain the metastable state of indeterminacy prior to cell fate decision-making and is consistent with biological observations. CONCLUSION: The general model presented here thus offers a novel principle for linking regulatory circuits with the state of indeterminacy characteristic of multipotent (stem cells.

  10. A General Model for Binary Cell Fate Decision Gene Circuits with Degeneracy: Indeterminacy and Switch Behavior in the Absence of Cooperativity

    Science.gov (United States)

    Andrecut, Mircea; Halley, Julianne D.; Winkler, David A.; Huang, Sui

    2011-01-01

    Background The gene regulatory circuit motif in which two opposing fate-determining transcription factors inhibit each other but activate themselves has been used in mathematical models of binary cell fate decisions in multipotent stem or progenitor cells. This simple circuit can generate multistability and explains the symmetric “poised” precursor state in which both factors are present in the cell at equal amounts as well as the resolution of this indeterminate state as the cell commits to either cell fate characterized by an asymmetric expression pattern of the two factors. This establishes the two alternative stable attractors that represent the two fate options. It has been debated whether cooperativity of molecular interactions is necessary to produce such multistability. Principal Findings Here we take a general modeling approach and argue that this question is not relevant. We show that non-linearity can arise in two distinct models in which no explicit interaction between the two factors is assumed and that distinct chemical reaction kinetic formalisms can lead to the same (generic) dynamical system form. Moreover, we describe a novel type of bifurcation that produces a degenerate steady state that can explain the metastable state of indeterminacy prior to cell fate decision-making and is consistent with biological observations. Conclusion The general model presented here thus offers a novel principle for linking regulatory circuits with the state of indeterminacy characteristic of multipotent (stem) cells. PMID:21625586

  11. Hidden attractors in dynamical models of phase-locked loop circuits: Limitations of simulation in MATLAB and SPICE

    Science.gov (United States)

    Kuznetsov, N. V.; Leonov, G. A.; Yuldashev, M. V.; Yuldashev, R. V.

    2017-10-01

    During recent years it has been shown that hidden oscillations, whose basin of attraction does not overlap with small neighborhoods of equilibria, may significantly complicate simulation of dynamical models, lead to unreliable results and wrong conclusions, and cause serious damage in drilling systems, aircrafts control systems, electromechanical systems, and other applications. This article provides a survey of various phase-locked loop based circuits (used in satellite navigation systems, optical, and digital communication), where such difficulties take place in MATLAB and SPICE. Considered examples can be used for testing other phase-locked loop based circuits and simulation tools, and motivate the development and application of rigorous analytical methods for the global analysis of phase-locked loop based circuits.

  12. Iterative experiment design guides the characterization of a light-inducible gene expression circuit.

    Science.gov (United States)

    Ruess, Jakob; Parise, Francesca; Milias-Argeitis, Andreas; Khammash, Mustafa; Lygeros, John

    2015-06-30

    Systems biology rests on the idea that biological complexity can be better unraveled through the interplay of modeling and experimentation. However, the success of this approach depends critically on the informativeness of the chosen experiments, which is usually unknown a priori. Here, we propose a systematic scheme based on iterations of optimal experiment design, flow cytometry experiments, and Bayesian parameter inference to guide the discovery process in the case of stochastic biochemical reaction networks. To illustrate the benefit of our methodology, we apply it to the characterization of an engineered light-inducible gene expression circuit in yeast and compare the performance of the resulting model with models identified from nonoptimal experiments. In particular, we compare the parameter posterior distributions and the precision to which the outcome of future experiments can be predicted. Moreover, we illustrate how the identified stochastic model can be used to determine light induction patterns that make either the average amount of protein or the variability in a population of cells follow a desired profile. Our results show that optimal experiment design allows one to derive models that are accurate enough to precisely predict and regulate the protein expression in heterogeneous cell populations over extended periods of time.

  13. Emergent bimodality and switch induced by time delays and noises in a synthetic gene circuit

    Science.gov (United States)

    Zhang, Chun; Du, Liping; Xie, Qingshuang; Wang, Tonghuan; Zeng, Chunhua; Nie, Linru; Duan, Weilong; Jia, Zhenglin; Wang, Canjun

    2017-10-01

    Based on the kinetic model for obtaining emergent bistability proposed by Tan et al. (2009), the effects of the fluctuations of protein synthesis rate and maximum dilution rate, the cross-correlation between two noises, and the time delay and the strength of the feedback loop in the synthetic gene circuit have been investigated through theoretical analysis and numerical simulation. Our results show that: (i) the fluctuations of protein synthesis rate and maximum dilution rate enhance the emergent bimodality of the probability distribution phenomenon, while the cross-correlation between two noises(λ), the time delay(τ) and the strength of the feedback loop(K) cause it to disappear; and (ii) the mean first passage time(MFPT) as functions of the noise strengths exhibits a maximum, this maximum is called noise-delayed switching (NDS) of the high concentration state. The NDS phenomenon shows that the noise can modify the stability of a metastable system in a counterintuitive way, the system remains in the metastable state for a longer time compared to the deterministic case. And the τ and the K enhances the stability of the ON state. The physical mechanisms for the switch between the ON and OFF states can be explained from the point of view of the effective potential.

  14. How to Efficiently Reconfigure Tunable Lookup Tables for Dynamic Circuit Specialization

    Directory of Open Access Journals (Sweden)

    Amit Kulkarni

    2016-01-01

    Full Text Available Dynamic Circuit Specialization is used to optimize the implementation of a parameterized application on an FPGA. Instead of implementing the parameters as regular inputs, in the DCS approach these inputs are implemented as constants. When the parameter values change, the design is reoptimized for the new constant values by reconfiguring the FPGA. This allows faster and more resource-efficient implementation but investigations have shown that reconfiguration time is the major limitation for DCS implementation on Xilinx FPGAs. The limitation arises from the use of inefficient reconfiguration methods in conventional DCS implementation. To address this issue, we propose different approaches to reduce the reconfiguration time drastically and improve the reconfiguration speed. In this context, this paper presents the use of custom reconfiguration controllers and custom reconfiguration software drivers, along with placement constraints to shorten the reconfiguration time. Our results show an improvement in the reconfiguration speed by at least a factor 14 by using Xilinx reconfiguration controller along with placement constraints. However, the improvement can go up to a factor 40 with the combination of a custom reconfiguration controller, custom software drivers, and placement constraints. We also observe depreciation in the system’s performance by at least 6% due to placement constraints.

  15. The neural circuit and synaptic dynamics underlying perceptual decision-making

    Science.gov (United States)

    Liu, Feng

    2015-03-01

    Decision-making with several choice options is central to cognition. To elucidate the neural mechanisms of multiple-choice motion discrimination, we built a continuous recurrent network model to represent a local circuit in the lateral intraparietal area (LIP). The network is composed of pyramidal cells and interneurons, which are directionally tuned. All neurons are reciprocally connected, and the synaptic connectivity strength is heterogeneous. Specifically, we assume two types of inhibitory connectivity to pyramidal cells: opposite-feature and similar-feature inhibition. The model accounted for both physiological and behavioral data from monkey experiments. The network is endowed with slow excitatory reverberation, which subserves the buildup and maintenance of persistent neural activity, and predominant feedback inhibition, which underlies the winner-take-all competition and attractor dynamics. The opposite-feature and opposite-feature inhibition have different effects on decision-making, and only their combination allows for a categorical choice among 12 alternatives. Together, our work highlights the importance of structured synaptic inhibition in multiple-choice decision-making processes.

  16. A Coupled Dynamical Model of Redox Flow Battery Based on Chemical Reaction, Fluid Flow, and Electrical Circuit

    OpenAIRE

    Li, Minghua; Hikihara, Takashi

    2008-01-01

    The redox (Reduction-Oxidation) flow battery is one of the most promising rechargeable batteries due to its ability to average loads and output of power sources. The transient characteristics are well known as the remarkable feature of the battery. Then it can also compensate for a sudden voltage drop. The dynamics are governed by the chemical reactions, fluid flow, and electrical circuit of its structure. This causes the difficulty of the analysis at transient state. This paper discusses the...

  17. 116 dB dynamic range CMOS readout circuit for MEMS capacitive accelerometer

    Science.gov (United States)

    Shanli, Long; Yan, Liu; Kejun, He; Xinggang, Tang; Qian, Chen

    2014-09-01

    A high stability in-circuit reprogrammable technique control system for a capacitive MEMS accelerometer is presented. Modulation and demodulation are used to separate the signal from the low frequency noise. A low-noise low-offset charge integrator is employed in this circuit to implement a capacitance-to-voltage converter and minimize the noise and offset. The application-specific integrated circuit (ASIC) is fabricated in a 0.5 μm one-ploy three-metal CMOS process. The measured results of the proposed circuit show that the noise floor of the ASIC is -116 dBV, the sensitivity of the accelerometer is 66 mV/g with a nonlinearity of 0.5%. The chip occupies 3.5 × 2.5 mm2 and the current is 3.5 mA.

  18. The impact of monochloramine on the diversity and dynamics of Legionella pneumophila subpopulations in a nuclear power plant cooling circuit.

    Science.gov (United States)

    Jakubek, Delphine; Le Brun, Matthieu; Leblon, Gerard; DuBow, Michael; Binet, Marie

    2013-08-01

    Members of the pathogenic Legionella genus encounter suitable growth conditions in nuclear power plant cooling circuits. To limit its proliferation and ensure that levels remain below regulatory thresholds, chemical treatment with monochloramine can be used in continuous or sequential conditions. The aim of this study was to determine the impact of monochloramine on L. pneumophila subpopulations in the cooling circuits of a nuclear power plant. The chosen procedure involved monitoring the diversity and dynamics of L. pneumophila subpopulations every month over the course of a year in a nuclear power plant cooling circuit, which was treated for 2 months during the period under study. This study confirmed the effectiveness of monochloramine to limit L. pneumophila concentrations in cooling circuits. The culturable L. pneumophila community was strongly affected by the injection of monochloramine. Several subpopulations persisted during treatment at low concentrations (below the detection limit of standard methods), suggesting that the susceptibility of L. pneumophila is strain dependent. Although the composition of the subpopulations was not similar, the resilience of the community structure was observed. Indeed, the community eventually returned to its initial structure and presented a similar pattern of richness, diversity and uniformity to that seen before treatment.

  19. An implantable wireless neural interface for recording cortical circuit dynamics in moving primates

    Science.gov (United States)

    Borton, David A.; Yin, Ming; Aceros, Juan; Nurmikko, Arto

    2013-04-01

    Objective. Neural interface technology suitable for clinical translation has the potential to significantly impact the lives of amputees, spinal cord injury victims and those living with severe neuromotor disease. Such systems must be chronically safe, durable and effective. Approach. We have designed and implemented a neural interface microsystem, housed in a compact, subcutaneous and hermetically sealed titanium enclosure. The implanted device interfaces the brain with a 510k-approved, 100-element silicon-based microelectrode array via a custom hermetic feedthrough design. Full spectrum neural signals were amplified (0.1 Hz to 7.8 kHz, 200× gain) and multiplexed by a custom application specific integrated circuit, digitized and then packaged for transmission. The neural data (24 Mbps) were transmitted by a wireless data link carried on a frequency-shift-key-modulated signal at 3.2 and 3.8 GHz to a receiver 1 m away by design as a point-to-point communication link for human clinical use. The system was powered by an embedded medical grade rechargeable Li-ion battery for 7 h continuous operation between recharge via an inductive transcutaneous wireless power link at 2 MHz. Main results. Device verification and early validation were performed in both swine and non-human primate freely-moving animal models and showed that the wireless implant was electrically stable, effective in capturing and delivering broadband neural data, and safe for over one year of testing. In addition, we have used the multichannel data from these mobile animal models to demonstrate the ability to decode neural population dynamics associated with motor activity. Significance. We have developed an implanted wireless broadband neural recording device evaluated in non-human primate and swine. The use of this new implantable neural interface technology can provide insight into how to advance human neuroprostheses beyond the present early clinical trials. Further, such tools enable mobile

  20. A 35fJ/Step differential successive approximation capacitive sensor readout circuit with quasi-dynamic operation

    KAUST Repository

    Omran, Hesham

    2016-10-06

    We propose a successive-approximation capacitive sensor readout circuit that achieves 35fJ/Step energy efficiency FoM, which represents 4× improvement over the state-of-the-art. A fully differential architecture is employed to provide robustness against common mode noise and errors. An inverter-based amplifier with near-threshold biasing provides robust, fast, and energy-efficient operation. Quasi-dynamic operation is used to maintain the energy efficiency for a scalable sample rate. A hybrid coarse-fine capacitive DAC achieves 11.7bit effective resolution in a compact area. © 2016 IEEE.

  1. Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy.

    Science.gov (United States)

    Neubauer, Florian B; Sederberg, Audrey; MacLean, Jason N

    2014-01-01

    During the generalization of epileptic seizures, pathological activity in one brain area recruits distant brain structures into joint synchronous discharges. However, it remains unknown whether specific changes in local circuit activity are related to the aberrant recruitment of anatomically distant structures into epileptiform discharges. Further, it is not known whether aberrant areas recruit or entrain healthy ones into pathological activity. Here we study the dynamics of local circuit activity during the spread of epileptiform discharges in the zero-magnesium in vitro model of epilepsy. We employ high-speed multi-photon imaging in combination with dual whole-cell recordings in acute thalamocortical (TC) slices of the juvenile mouse to characterize the generalization of epileptic activity between neocortex and thalamus. We find that, although both structures are exposed to zero-magnesium, the initial onset of focal epileptiform discharge occurs in cortex. This suggests that local recurrent connectivity that is particularly prevalent in cortex is important for the initiation of seizure activity. Subsequent recruitment of thalamus into joint, generalized discharges is coincident with an increase in the coherence of local cortical circuit activity that itself does not depend on thalamus. Finally, the intensity of population discharges is positively correlated between both brain areas. This suggests that during and after seizure generalization not only the timing but also the amplitude of epileptiform discharges in thalamus is entrained by cortex. Together these results suggest a central role of neocortical activity for the onset and the structure of pathological recruitment of thalamus into joint synchronous epileptiform discharges.

  2. A 97 dB dynamic range CSA-based readout circuit with analog temperature compensation for MEMS capacitive sensors

    Science.gov (United States)

    Tao, Yin; Chong, Zhang; Huanming, Wu; Qisong, Wu; Haigang, Yang

    2013-11-01

    This paper presents a charge-sensitive-amplifier (CSA) based readout circuit for capacitive microelectro-mechanical-system (MEMS) sensors. A continuous-time (CT) readout structure using the chopper technique is adopted to cancel the low frequency noise and improve the resolution of the readout circuits. An operational trans-conductance amplifier (OTA) structure with an auxiliary common-mode-feedback-OTA is proposed in the fully differential CSA to suppress the chopper modulation induced disturbance at the OTA input terminal. An analog temperature compensation method is proposed, which adjusts the chopper signal amplitude with temperature variation to compensate the temperature drift of the CSA readout sensitivity. The chip is designed and implemented in a 0.35 μm CMOS process and is 2.1 × 2.1 mm2 in area. The measurement shows that the readout circuit achieves 0.9 aF / √Hz capacitive resolution, 97 dB dynamic range in 100 Hz signal bandwidth, and 0.8 mV/fF sensitivity with a temperature drift of 35 ppm/°C after optimized compensation.

  3. Parameter estimation methods for gene circuit modeling from time-series mRNA data: a comparative study

    KAUST Repository

    Fan, M.

    2015-03-29

    Parameter estimation is a challenging computational problemin the reverse engineering of biological systems. Because advances in biotechnology have facilitated wide availability of time-series gene expression data, systematic parameter esti- mation of gene circuitmodels fromsuch time-series mRNA data has become an importantmethod for quantitatively dissecting the regulation of gene expression. By focusing on themodeling of gene circuits, we examine here the perform- ance of three types of state-of-the-art parameter estimation methods: population-basedmethods, onlinemethods and model-decomposition-basedmethods. Our results show that certain population-basedmethods are able to generate high- quality parameter solutions. The performance of thesemethods, however, is heavily dependent on the size of the param- eter search space, and their computational requirements substantially increase as the size of the search space increases. In comparison, onlinemethods andmodel decomposition-basedmethods are computationally faster alternatives and are less dependent on the size of the search space. Among other things, our results show that a hybrid approach that augments computationally fastmethods with local search as a subsequent refinement procedure can substantially increase the qual- ity of their parameter estimates to the level on par with the best solution obtained fromthe population-basedmethods whilemaintaining high computational speed. These suggest that such hybridmethods can be a promising alternative to themore commonly used population-basedmethods for parameter estimation of gene circuit models when limited prior knowledge about the underlying regulatorymechanismsmakes the size of the parameter search space vastly large. © The Author 2015. Published by Oxford University Press.

  4. LTS and FS inhibitory interneurons, short-term synaptic plasticity, and cortical circuit dynamics.

    Directory of Open Access Journals (Sweden)

    Itai Hayut

    2011-10-01

    Full Text Available Somatostatin-expressing, low threshold-spiking (LTS cells and fast-spiking (FS cells are two common subtypes of inhibitory neocortical interneuron. Excitatory synapses from regular-spiking (RS pyramidal neurons to LTS cells strongly facilitate when activated repetitively, whereas RS-to-FS synapses depress. This suggests that LTS neurons may be especially relevant at high rate regimes and protect cortical circuits against over-excitation and seizures. However, the inhibitory synapses from LTS cells usually depress, which may reduce their effectiveness at high rates. We ask: by which mechanisms and at what firing rates do LTS neurons control the activity of cortical circuits responding to thalamic input, and how is control by LTS neurons different from that of FS neurons? We study rate models of circuits that include RS cells and LTS and FS inhibitory cells with short-term synaptic plasticity. LTS neurons shift the RS firing-rate vs. current curve to the right at high rates and reduce its slope at low rates; the LTS effect is delayed and prolonged. FS neurons always shift the curve to the right and affect RS firing transiently. In an RS-LTS-FS network, FS neurons reach a quiescent state if they receive weak input, LTS neurons are quiescent if RS neurons receive weak input, and both FS and RS populations are active if they both receive large inputs. In general, FS neurons tend to follow the spiking of RS neurons much more closely than LTS neurons. A novel type of facilitation-induced slow oscillations is observed above the LTS firing threshold with a frequency determined by the time scale of recovery from facilitation. To conclude, contrary to earlier proposals, LTS neurons affect the transient and steady state responses of cortical circuits over a range of firing rates, not only during the high rate regime; LTS neurons protect against over-activation about as well as FS neurons.

  5. Anti-Tamper Method for Field Programmable Gate Arrays Through Dynamic Reconfiguration and Decoy Circuits

    Science.gov (United States)

    2008-03-27

    Reconfigurable FPGAs”. IEICE Trans. Fundam. Electron . Commun. Comput. Sci., E89-A(12):3416–3426, 2006. ISSN 0916-8508. 42. Tseng, C. “Lock Your Designs...Implementation of the Advanced Encryption Standard”. IEEE Transactions on Computers, 52(4):493–505, April 2003. URL http://euler.ecs.umass.edu/research...Bushnell, Vishwani D. Agrawal. Essentials of Electronic Testing for Digital Memory & Mixed-Signal VLSI Circuits. Springer, 2000. ISBN 0-7923- 7991-8. 35

  6. Equivalent circuit-based analysis of CMUT cell dynamics in arrays.

    Science.gov (United States)

    Oguz, H K; Atalar, Abdullah; Köymen, Hayrettin

    2013-05-01

    Capacitive micromachined ultrasonic transducers (CMUTs) are usually composed of large arrays of closely packed cells. In this work, we use an equivalent circuit model to analyze CMUT arrays with multiple cells. We study the effects of mutual acoustic interactions through the immersion medium caused by the pressure field generated by each cell acting upon the others. To do this, all the cells in the array are coupled through a radiation impedance matrix at their acoustic terminals. An accurate approximation for the mutual radiation impedance is defined between two circular cells, which can be used in large arrays to reduce computational complexity. Hence, a performance analysis of CMUT arrays can be accurately done with a circuit simulator. By using the proposed model, one can very rapidly obtain the linear frequency and nonlinear transient responses of arrays with an arbitrary number of CMUT cells. We performed several finite element method (FEM) simulations for arrays with small numbers of cells and showed that the results are very similar to those obtained by the equivalent circuit model.

  7. Electronic Circuit Analog of Synthetic Genetic Networks: Revisited

    CERN Document Server

    Hellen, Edward H

    2016-01-01

    Electronic circuits are useful tools for studying potential dynamical behaviors of synthetic genetic networks. The circuit models are complementary to numerical simulations of the networks, especially providing a framework for verification of dynamical behaviors in the presence of intrinsic and extrinsic noise of the electrical systems. Here we present an improved version of our previous design of an electronic analog of genetic networks that includes the 3-gene Repressilator and we show conversions between model parameters and real circuit component values to mimic the numerical results in experiments. Important features of the circuit design include the incorporation of chemical kinetics representing Hill function inhibition, quorum sensing coupling, and additive noise. Especially, we make a circuit design for a systematic change of initial conditions in experiment, which is critically important for studies of dynamical systems' behavior, particularly, when it shows multistability. This improved electronic ...

  8. System identification of the nonlinear dynamics in the thalamocortical circuit in response to patterned thalamic microstimulation in-vivo

    Science.gov (United States)

    Millard, Daniel C; Wang, Qi; Gollnick, Clare A; Stanley, Garrett B

    2013-01-01

    Objective Nonlinear system identification approaches were used to develop a dynamical model of the network level response to patterns of microstimulation in-vivo. Approach The thalamocortical circuit of the rodent vibrissa pathway was the model system, with voltage sensitive dye imaging capturing the cortical response to patterns of stimulation delivered from a single electrode in the ventral posteromedial thalamus. The results of simple paired stimulus experiments formed the basis for the development of a phenomenological model explicitly containing nonlinear elements observed experimentally. The phenomenological model was fit using datasets obtained with impulse train inputs, Poisson-distributed in time and uniformly varying in amplitude. Main Results The phenomenological model explained 58% of the variance in the cortical response to out of sample patterns of thalamic microstimulation. Furthermore, while fit on trial averaged data, the phenomenological model reproduced single trial response properties when simulated with noise added into the system during stimulus presentation. The simulations indicate that the single trial response properties were dependent on the relative sensitivity of the static nonlinearities in the two stages of the model, and ultimately suggest that electrical stimulation activates local circuitry through linear recruitment, but that this activity propagates in a highly nonlinear fashion to downstream targets. Significance The development of nonlinear dynamical models of neural circuitry will guide information delivery for sensory prosthesis applications, and more generally reveal properties of population coding within neural circuits. PMID:24162186

  9. System identification of the nonlinear dynamics in the thalamocortical circuit in response to patterned thalamic microstimulation in vivo

    Science.gov (United States)

    Millard, Daniel C.; Wang, Qi; Gollnick, Clare A.; Stanley, Garrett B.

    2013-12-01

    Objective. Nonlinear system identification approaches were used to develop a dynamical model of the network level response to patterns of microstimulation in vivo. Approach. The thalamocortical circuit of the rodent vibrissa pathway was the model system, with voltage sensitive dye imaging capturing the cortical response to patterns of stimulation delivered from a single electrode in the ventral posteromedial thalamus. The results of simple paired stimulus experiments formed the basis for the development of a phenomenological model explicitly containing nonlinear elements observed experimentally. The phenomenological model was fit using datasets obtained with impulse train inputs, Poisson-distributed in time and uniformly varying in amplitude. Main results. The phenomenological model explained 58% of the variance in the cortical response to out of sample patterns of thalamic microstimulation. Furthermore, while fit on trial-averaged data, the phenomenological model reproduced single trial response properties when simulated with noise added into the system during stimulus presentation. The simulations indicate that the single trial response properties were dependent on the relative sensitivity of the static nonlinearities in the two stages of the model, and ultimately suggest that electrical stimulation activates local circuitry through linear recruitment, but that this activity propagates in a highly nonlinear fashion to downstream targets. Significance. The development of nonlinear dynamical models of neural circuitry will guide information delivery for sensory prosthesis applications, and more generally reveal properties of population coding within neural circuits.

  10. Dynamic Actin Gene Family Evolution in Primates

    Directory of Open Access Journals (Sweden)

    Liucun Zhu

    2013-01-01

    Full Text Available Actin is one of the most highly conserved proteins and plays crucial roles in many vital cellular functions. In most eukaryotes, it is encoded by a multigene family. Although the actin gene family has been studied a lot, few investigators focus on the comparison of actin gene family in relative species. Here, the purpose of our study is to systematically investigate characteristics and evolutionary pattern of actin gene family in primates. We identified 233 actin genes in human, chimpanzee, gorilla, orangutan, gibbon, rhesus monkey, and marmoset genomes. Phylogenetic analysis showed that actin genes in the seven species could be divided into two major types of clades: orthologous group versus complex group. Codon usages and gene expression patterns of actin gene copies were highly consistent among the groups because of basic functions needed by the organisms, but much diverged within species due to functional diversification. Besides, many great potential pseudogenes were found with incomplete open reading frames due to frameshifts or early stop codons. These results implied that actin gene family in primates went through “birth and death” model of evolution process. Under this model, actin genes experienced strong negative selection and increased the functional complexity by reproducing themselves.

  11. Nonlinear Companding Circuits With Thermal Compensation to Enhance Input Dynamic Range in Analog Optical Fiber Links

    Directory of Open Access Journals (Sweden)

    J. Rodríguez-Rodriguez

    2011-04-01

    Full Text Available Measuring systems based on a pair of optical fiber transmitter-receivers are used in medium-voltage testinglaboratories wherein the environment of high electromagnetic interference (EMI is a limitation for using conventionalcabling. Nonlinear compensation techniques have been used to limit the voltage range at the input of optical fiberlinks. However, nonlinear compensation introduces gain and linearity errors caused by thermal drift. This paperpresents a method of thermal compensation for the nonlinear circuit used to improve transient signal handlingcapabilities in measuring system while maintaining low errors in gain and linearity caused by thermal drift.

  12. Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data.

    Science.gov (United States)

    Schrader, Alexandra; Meyer, Katharina; Walther, Neele; Stolz, Ailine; Feist, Maren; Hand, Elisabeth; von Bonin, Frederike; Evers, Maurits; Kohler, Christian; Shirneshan, Katayoon; Vockerodt, Martina; Klapper, Wolfram; Szczepanowski, Monika; Murray, Paul G; Bastians, Holger; Trümper, Lorenz; Spang, Rainer; Kube, Dieter

    2016-07-26

    To discover new regulatory pathways in B lymphoma cells, we performed a combined analysis of experimental, clinical and global gene expression data. We identified a specific cluster of genes that was coherently expressed in primary lymphoma samples and suppressed by activation of the B cell receptor (BCR) through αIgM treatment of lymphoma cells in vitro. This gene cluster, which we called BCR.1, includes numerous cell cycle regulators. A reduced expression of BCR.1 genes after BCR activation was observed in different cell lines and also in CD10+ germinal center B cells. We found that BCR activation led to a delayed entry to and progression of mitosis and defects in metaphase. Cytogenetic changes were detected upon long-term αIgM treatment. Furthermore, an inverse correlation of BCR.1 genes with c-Myc co-regulated genes in distinct groups of lymphoma patients was observed. Finally, we showed that the BCR.1 index discriminates activated B cell-like and germinal centre B cell-like diffuse large B cell lymphoma supporting the functional relevance of this new regulatory circuit and the power of guided clustering for biomarker discovery.

  13. Experimental measurements and mathematical modeling of biological noise arising from transcriptional and translational regulation of basic synthetic gene circuits.

    Science.gov (United States)

    Bandiera, Lucia; Pasini, Alice; Pasotti, Lorenzo; Zucca, Susanna; Mazzini, Giuliano; Magni, Paolo; Giordano, Emanuele; Furini, Simone

    2016-04-21

    The small number of molecules, unevenly distributed within an isogenic cell population, makes gene expression a noisy process, and strategies have evolved to deal with this variability in protein concentration and to limit its impact on cellular behaviors. As translational efficiency has a major impact on biological noise, a possible strategy to control noise is to regulate gene expression processes at the post-transcriptional level. In this study, fluctuations in the concentration of a green fluorescent protein were compared, at the single cell level, upon transformation of an isogenic bacterial cell population with synthetic gene circuits implementing either a transcriptional or a post-transcriptional control of gene expression. Experimental measurements showed that protein variability is lower under post-transcriptional control, when the same average protein concentrations are compared. This effect is well reproduced by stochastic simulations, supporting the hypothesis that noise reduction is due to the control mechanism acting on the efficiency of translation. Similar strategies are likely to play a role in noise reduction in natural systems and to be useful for controlling noise in synthetic biology applications.

  14. Using mice to model Obsessive Compulsive Disorder: From genes to circuits.

    Science.gov (United States)

    Ahmari, Susanne E

    2016-05-03

    Obsessive Compulsive Disorder (OCD) is a severe, chronic, and highly prevalent psychiatric disorder that affects between 1.5% and 3% of people worldwide. Despite its severity, high prevalence, and clear societal cost, current OCD therapies are only partially effective. In order to ultimately develop improved treatments for this severe mental illness, we need further research to gain an improved understanding of the pathophysiology that underlies obsessions and compulsions. Though studies in OCD patients can provide some insight into the disease process, studies in humans are inherently limited in their ability to dissect pathologic processes because of their non-invasive nature. The recent development of strategies for genetic and circuit-specific manipulation in rodent models finally allows us to identify the molecular, cellular, and circuit events that lead to abnormal repetitive behaviors and affect dysregulation relevant to OCD. This review will highlight recent studies in mouse model systems that have used transgenic and optogenetic tools in combination with classic pharmacology and behavioral techniques to advance our understanding of these pathologic processes.

  15. Escherichia coli flagellar genes as target sites for integration and expression of genetic circuits.

    Directory of Open Access Journals (Sweden)

    Mario Juhas

    Full Text Available E. coli is a model platform for engineering microbes, so genetic circuit design and analysis will be greatly facilitated by simple and effective approaches to introduce genetic constructs into the E. coli chromosome at well-characterised loci. We combined the Red recombinase system of bacteriophage λ and Isothermal Gibson Assembly for rapid integration of novel DNA constructs into the E. coli chromosome. We identified the flagellar region as a promising region for integration and expression of genetic circuits. We characterised integration and expression at four candidate loci, fliD, fliS, fliT, and fliY, of the E. coli flagellar region 3a. The integration efficiency and expression from the four integrations varied considerably. Integration into fliD and fliS significantly decreased motility, while integration into fliT and fliY had only a minor effect on the motility. None of the integrations had negative effects on the growth of the bacteria. Overall, we found that fliT was the most suitable integration site.

  16. Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy

    Directory of Open Access Journals (Sweden)

    Florian B Neubauer

    2014-09-01

    Full Text Available During the generalization of epileptic seizures, pathological activity in one brain area recruits distant brain structures into joint synchronous discharges. However, it remains unknown whether specific changes in local circuit activity are related to the aberrant recruitment of anatomically distant structures into epileptiform discharges. Further, it is not known whether aberrant areas recruit or entrain healthy ones into pathological activity. Here we study the dynamics of local circuit activity during the spread of epileptiform discharges in the zero-magnesium in vitro model of epilepsy. We employ high-speed multi-photon imaging in combination with dual whole-cell recordings in acute thalamocortical slices of the juvenile mouse to characterize the generalization of epileptic activity between neocortex and thalamus. We find that, although both structures are exposed to zero-magnesium, the initial onset of focal epileptiform discharge occurs in cortex. This suggests that local recurrent connectivity that is particularly prevalent in cortex is important for the initiation of seizure activity. Subsequent recruitment of thalamus into joint, generalized discharges is coincident with an increase in the coherence of local cortical circuit activity that itself does not depend on thalamus. Finally, the intensity of population discharges is positively correlated between both brain areas. This suggests that during and after seizure generalization not only the timing but also the amplitude of epileptiform discharges in thalamus is entrained by cortex. Together these results suggest a central role of neocortical activity for the onset and the structure of pathological recruitment of thalamus into joint synchronous epileptiform discharges.

  17. Inferring slowly-changing dynamic gene-regulatory networks

    NARCIS (Netherlands)

    Wit, Ernst C.; Abbruzzo, Antonino

    2015-01-01

    Dynamic gene-regulatory networks are complex since the interaction patterns between their components mean that it is impossible to study parts of the network in separation. This holistic character of gene-regulatory networks poses a real challenge to any type of modelling. Graphical models are a cla

  18. Experimental verification of a thermal equivalent circuit dynamic model on an extended range electric vehicle battery pack

    Science.gov (United States)

    Ramotar, Lokendra; Rohrauer, Greg L.; Filion, Ryan; MacDonald, Kathryn

    2017-03-01

    The development of a dynamic thermal battery model for hybrid and electric vehicles is realized. A thermal equivalent circuit model is created which aims to capture and understand the heat propagation from the cells through the entire pack and to the environment using a production vehicle battery pack for model validation. The inclusion of production hardware and the liquid battery thermal management system components into the model considers physical and geometric properties to calculate thermal resistances of components (conduction, convection and radiation) along with their associated heat capacity. Various heat sources/sinks comprise the remaining model elements. Analog equivalent circuit simulations using PSpice are compared to experimental results to validate internal temperature nodes and heat rates measured through various elements, which are then employed to refine the model further. Agreement with experimental results indicates the proposed method allows for a comprehensive real-time battery pack analysis at little computational expense when compared to other types of computer based simulations. Elevated road and ambient conditions in Mesa, Arizona are simulated on a parked vehicle with varying quiescent cooling rates to examine the effect on the diurnal battery temperature for longer term static exposure. A typical daily driving schedule is also simulated and examined.

  19. An equivalent circuit approach to the modelling of the dynamics of dye sensitized solar cells

    DEFF Research Database (Denmark)

    Bay, L.; West, K.

    2005-01-01

    be calculated and used to optimize the photo electrode with respect to thickness and density. The result is mathematically equivalent to the usual approach for IMVS and IMPS modelling based on diffusion equations describing the transport of electrons in the semiconductor and on charge accumulation in traps......A model that can be used to interpret the response of a dye-sensitized photo electrode to intensity-modulated light (intensity modulated voltage spectroscopy, IMVS and intensity modulated photo-current spectroscopy, IMPS) is presented. The model is based on an equivalent circuit approach involving...... a transmission line with both an electrical and an ionic branch. An analytical expression including a term from the passive electrochemical impedance of the network, and a term accounting for the photo generation in the electrode is found. From this model IMVS and IMPS responses as well as W curves can...

  20. Analysis on Dynamic Dielectric Recovery and Statistical Property of Vacuum Circuit-Breakers with Multi-Breaks

    Institute of Scientific and Technical Information of China (English)

    廖敏夫; 段雄英; 邹积岩

    2004-01-01

    Based on the dynamic dielectric recovery process in the vacuum gaps in series, investigations were made on post-arc insulation state in double and multi-breaks operation in high voltage power system. From the research on the breakdown weak points in high voltage vacuum gaps, their turnout and distribution, some theoretic work were made to set up the models for describing the statistical property of multi-breaks vacuum circuit-breakers' breakdown and post-arc re-strike, which can be used for explaining the mechanism of the improvement in the breaking capacity of multi-breaks units compared with that of single-break ones which have the same equivalent gap length. The advantages of vacuum breakers with multi-breaks are proposed.

  1. Timing Analysis of Genetic Logic Circuits using D-VASim

    DEFF Research Database (Denmark)

    Baig, Hasan; Madsen, Jan

    A genetic logic circuit is a gene regulator network implemented by re-engineering the DNA of a cell, in order to controlgene expression or metabolic pathways, through a logic combination of external signals, such as chemicals or proteins. As for electroniclogic circuits, timing and propagation...... delay analysis may play a very significant role in the designing of genetic logic circuits. In thisdemonstration, we present the capability of D-VASim (Dynamic Virtual Analyzer and Simulator) to perform the timing and propagationdelay analysis of genetic logic circuits. Using D-VASim, the timing...... and propagation delay analysis of single as well as cascaded geneticlogic circuits can be performed. D-VASim allows user to change the circuit parameters during runtime simulation to observe its effectson circuit’s timing behavior. The results obtained from D-VASim can be used not only to characterize the timing...

  2. Development of a Dynamic Population Balance Plant Simulator for Mineral Processing Circuits

    National Research Council Canada - National Science Library

    Fatemeh Khoshnam; Mohammad reza Khalesi; Ahmad Khodadadi Darban; Mohammad Javad Zarei

    2015-01-01

    .... The dynamic simulator of each mentioned unit was also developedaccording to population balance models with the help of MATLAB/Simulink environment and wasverified against the data from the literature...

  3. Modeling in fast dynamics of accidents in the primary circuit of PWR type reactors; Modelisation en dynamique rapide d'accidents dans le circuit primaire des reacteurs a eau pressurisee

    Energy Technology Data Exchange (ETDEWEB)

    Robbe, M.F

    2003-12-01

    Two kinds of accidents, liable to occur in the primary circuit of a Pressurized Water Reactor and involving fast dynamic phenomena, are analyzed. The Loss Of Coolant Accident (LOCA) is the accident used to define the current PWR. It consists in a large-size break located in a pipe of the primary circuit. A blowdown wave propagates through the circuit. The pressure differences between the different zones of the reactor induce high stresses in the structures of the lower head and may degrade the reactor core. The primary circuit starts emptying from the break opening. Pressure decreases very quickly, involving a large steaming. Two thermal-hydraulic simulations of the blowdown phase of a LOCA are computed with the Europlexus code. The primary circuit is represented by a pipe-model including the hydraulic peculiarities of the circuit. The main differences between both computations concern the kind of reactor, the break location and model, and the initialization of the accidental operation. Steam explosion is a hypothetical severe accident liable to happen after a core melting. The molten part of the core (called corium) falls in the lower part of the reactor. The interaction between the hot corium and the cold water remaining at the bottom of the vessel induces a massive and violent vaporization of water, similar to an explosive phenomenon. A shock wave propagates in the vessel. what can damage seriously the neighbouring structures or drill the vessel. This work presents a synthesis of in-vessel parametrical studies carried out with the Europlexus code, the linkage of the thermal-hydraulic code Mc3d dedicated to the pre-mixing phase with the Europlexus code dealing with the explosion, and finally a benchmark between the Cigalon and Europlexus codes relative to the Vulcano mock-up. (author)

  4. Dynamic divisive normalization predicts time-varying value coding in decision-related circuits.

    Science.gov (United States)

    Louie, Kenway; LoFaro, Thomas; Webb, Ryan; Glimcher, Paul W

    2014-11-26

    Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding.

  5. New regulatory circuit controlling spatial and temporal gene expression in the sea urchin embryo oral ectoderm GRN.

    Science.gov (United States)

    Li, Enhu; Materna, Stefan C; Davidson, Eric H

    2013-10-01

    The sea urchin oral ectoderm gene regulatory network (GRN) model has increased in complexity as additional genes are added to it, revealing its multiple spatial regulatory state domains. The formation of the oral ectoderm begins with an oral-aboral redox gradient, which is interpreted by the cis-regulatory system of the nodal gene to cause its expression on the oral side of the embryo. Nodal signaling drives cohorts of regulatory genes within the oral ectoderm and its derived subdomains. Activation of these genes occurs sequentially, spanning the entire blastula stage. During this process the stomodeal subdomain emerges inside of the oral ectoderm, and bilateral subdomains defining the lateral portions of the future ciliary band emerge adjacent to the central oral ectoderm. Here we examine two regulatory genes encoding repressors, sip1 and ets4, which selectively prevent transcription of oral ectoderm genes until their expression is cleared from the oral ectoderm as an indirect consequence of Nodal signaling. We show that the timing of transcriptional de-repression of sip1 and ets4 targets which occurs upon their clearance explains the dynamics of oral ectoderm gene expression. In addition two other repressors, the direct Nodal target not, and the feed forward Nodal target goosecoid, repress expression of regulatory genes in the central animal oral ectoderm thereby confining their expression to the lateral domains of the animal ectoderm. These results have permitted construction of an enhanced animal ectoderm GRN model highlighting the repressive interactions providing precise temporal and spatial control of regulatory gene expression. © 2013 Elsevier Inc. All rights reserved.

  6. Frontostriatal Circuit Dynamics Correlate with Cocaine Cue-Evoked Behavioral Arousal during Early Abstinence.

    Science.gov (United States)

    Smith, Wesley C; Rosenberg, Matthew H; Claar, Leslie D; Chang, Victoria; Shah, Sagar N; Walwyn, Wendy M; Evans, Christopher J; Masmanidis, Sotiris C

    2016-01-01

    It is thought that frontostriatal circuits play an important role in mediating conditioned behavioral responses to environmental stimuli that were previously encountered during drug administration. However, the neural correlates of conditioned responses to drug-associated cues are not well understood at the level of large populations of simultaneously recorded neurons, or at the level of local field potential (LFP) synchrony in the frontostriatal network. Here we introduce a behavioral assay of conditioned arousal to cocaine cues involving pupillometry in awake head-restrained mice. After just 24 h of drug abstinence, brief exposures to olfactory stimuli previously paired with cocaine injections led to a transient dilation of the pupil, which was greater than the dilation effect to neutral cues. In contrast, there was no cue-selective change in locomotion, as measured by the rotation of a circular treadmill. The behavioral assay was combined with simultaneous recordings from dozens of electrophysiologically identified units in the medial prefrontal cortex (mPFC) and ventral striatum (VS). We found significant relationships between cocaine cue-evoked pupil dilation and the proportion of inhibited principal cells in the mPFC and VS. Additionally, LFP coherence analysis revealed a significant correlation between pupillary response and synchrony in the 25-45 Hz frequency band. Together, these results show that pupil dilation is sensitive to drug-associated cues during acute stages of abstinence, and that individual animal differences in this behavioral arousal response can be explained by two complementary measures of frontostriatal network activity.

  7. Real-Time Nanoscale Open-Circuit Voltage Dynamics of Perovskite Solar Cells.

    Science.gov (United States)

    Garrett, Joseph L; Tennyson, Elizabeth M; Hu, Miao; Huang, Jinsong; Munday, Jeremy N; Leite, Marina S

    2017-04-12

    Hybrid organic-inorganic perovskites based on methylammonium lead (MAPbI3) are an emerging material with great potential for high-performance and low-cost photovoltaics. However, for perovskites to become a competitive and reliable solar cell technology their instability and spatial variation must be understood and controlled. While the macroscopic characterization of the devices as a function of time is very informative, a nanoscale identification of their real-time local optoelectronic response is still missing. Here, we implement a four-dimensional imaging method through illuminated heterodyne Kelvin probe force microscopy to spatially (perovskite solar cells in a low relative humidity environment. Local open-circuit voltage (Voc) images show nanoscale sites with voltage variation >300 mV under 1-sun illumination. Surprisingly, regions of voltage that relax in seconds and after several minutes consistently coexist. Time-dependent changes of the local Voc are likely due to intragrain ion migration and are reversible at low injection level. These results show for the first time the real-time transient behavior of the Voc in perovskite solar cells at the nanoscale. Understanding and controlling the light-induced electrical changes that affect device performance are critical to the further development of stable perovskite-based solar technologies.

  8. Systems mechanobiology: tension-inhibited protein turnover is sufficient to physically control gene circuits.

    Science.gov (United States)

    Dingal, P C Dave P; Discher, Dennis E

    2014-12-02

    Mechanotransduction pathways convert forces that stress and strain structures within cells into gene expression levels that impact development, homeostasis, and disease. The levels of some key structural proteins in the nucleus, cytoskeleton, or extracellular matrix have been recently reported to scale with tissue- and cell-level forces or mechanical properties such as stiffness, and so the mathematics of mechanotransduction becomes important to understand. Here, we show that if a given structural protein positively regulates its own gene expression, then stresses need only inhibit degradation of that protein to achieve stable, mechanosensitive gene expression. This basic use-it-or-lose-it module is illustrated by application to meshworks of nuclear lamin A, minifilaments of myosin II, and extracellular matrix collagen fibers—all of which possess filamentous coiled-coil/supercoiled structures. Past experiments not only suggest that tension suppresses protein degradation mediated and/or initiated by various enzymes but also that transcript levels vary with protein levels because key transcription factors are regulated by these structural proteins. Coupling between modules occurs within single cells and between cells in tissue, as illustrated during embryonic heart development where cardiac fibroblasts make collagen that cardiomyocytes contract. With few additional assumptions, the basic module has sufficient physics to control key structural genes in both development and disease.

  9. Tool for a configurable integrated circuit that uses determination of dynamic power consumption

    Science.gov (United States)

    French, Matthew C. (Inventor); Wang, Li (Inventor); Agarwal, Deepak (Inventor); Davoodi, Azadeh (Inventor)

    2011-01-01

    A configurable logic tool that allows minimization of dynamic power within an FPGA design without changing user-entered specifications. The minimization of power may use minimized clock nets as a first order operation, and a second order operation that minimizes other factors, such as area of placement, area of clocks and/or slack.

  10. Synchronizing Hyperchaotic Circuits

    DEFF Research Database (Denmark)

    Tamasevicius, Arunas; Cenys, Antanas; Namajunas, Audrius

    1997-01-01

    Regarding possible applications to secure communications the technique of synchronizing hyperchaotic circuits with a single dynamical variable is discussed. Several specific examples including the fourth-order circuits with two positive Lyapunov exponents as well as the oscillator with a delay line...... characterized by multiple positive Lyapunov exponents are reviewd....

  11. Coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites for the detection of BCR/ABL fusion gene

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xueping [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Wang, Li [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Department of Medical Laboratory, Chongqing Emergency Medical Center (Chongqing The Fourth Hospital), Chongqing, 400016 (China); Sheng, Shangchun [The No.2 Peoples' Hospital of Yibin, Sichuan, 644000 (China); Wang, Teng; Yang, Juan [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Xie, Guoming, E-mail: guomingxie@cqmu.edu.cn [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Feng, Wenli, E-mail: fengwlcqmu@sina.com [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China)

    2015-08-19

    This article described a novel method by coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites (GS/PANI/AuNPs) for highly sensitive and specific detection of BCR/ABL fusion gene (bcr/abl) in chronic myeloid leukemia (CML). DNA circuit known as catalyzed hairpin assembly (CHA) is enzyme-free and can be simply operated to achieve exponential amplification, which has been widely employed in biosensing. However, application of CHA has been hindered by the need of specially redesigned sequences for each single-stranded DNA input. Herein, a transducer hairpin (HP) was designed to obtain a universal DNA circuit with favorable signal-to-background ratio. To further improve signal amplification, GS/PANI/AuNPs with excellent conductivity and enlarged effective area were introduced into this DNA circuit. Consequently, by combining the advantages of CHA and GS/PANI/AuNPs, bcr/abl could be detected in a linear range from 10 pM to 20 nM with a detection limit of 1.05 pM. Moreover, this protocol showed excellent specificity, good stability and was successfully applied for the detection of real sample, which demonstrated its great potential in clinical application. - Highlights: • A transducer hairpin was designed to improve the versatility of DNA circuit. • GS/PANI/AuNPs were introduced to the DNA circuit for further signal amplification. • The established biosensor displayed high sensitivity and good specificity.

  12. Brain circuit-gene expression relationships and neuroplasticity of multisensory cortices in blind children.

    Science.gov (United States)

    Ortiz-Terán, Laura; Diez, Ibai; Ortiz, Tomás; Perez, David L; Aragón, Jose Ignacio; Costumero, Victor; Pascual-Leone, Alvaro; El Fakhri, Georges; Sepulcre, Jorge

    2017-06-27

    Sensory deprivation reorganizes neurocircuits in the human brain. The biological basis of such neuroplastic adaptations remains elusive. In this study, we applied two complementary graph theory-based functional connectivity analyses, one to evaluate whole-brain functional connectivity relationships and the second to specifically delineate distributed network connectivity profiles downstream of primary sensory cortices, to investigate neural reorganization in blind children compared with sighted controls. We also examined the relationship between connectivity changes and neuroplasticity-related gene expression profiles in the cerebral cortex. We observed that multisensory integration areas exhibited enhanced functional connectivity in blind children and that this reorganization was spatially associated with the transcription levels of specific members of the cAMP Response Element Binding protein gene family. Using systems-level analyses, this study advances our understanding of human neuroplasticity and its genetic underpinnings following sensory deprivation.

  13. Can terminators be used as insulators into yeast synthetic gene circuits?

    OpenAIRE

    Song, Wenjiang; Li, Jing; Liang, Qiang; Marchisio, Mario Andrea

    2016-01-01

    Background In bacteria, transcription units can be insulated by placing a terminator in front of a promoter. In this way promoter leakage due to the read-through from an upstream gene or RNA polymerase unspecific binding to the DNA is, in principle, removed. Differently from bacterial terminators, yeast S. cerevisiae terminators contain a hexamer sequence, the efficiency element, that strongly resembles the eukaryotic TATA box i.e. the promoter sequence recognized and bound by RNA polymerase ...

  14. A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila.

    Science.gov (United States)

    Saito, Kuniaki; Inagaki, Sachi; Mituyama, Toutai; Kawamura, Yoshinori; Ono, Yukiteru; Sakota, Eri; Kotani, Hazuki; Asai, Kiyoshi; Siomi, Haruhiko; Siomi, Mikiko C

    2009-10-29

    PIWI-interacting RNAs (piRNAs) silence retrotransposons in Drosophila germ lines by associating with the PIWI proteins Argonaute 3 (AGO3), Aubergine (Aub) and Piwi. piRNAs in Drosophila are produced from intergenic repetitive genes and piRNA clusters by two systems: the primary processing pathway and the amplification loop. The amplification loop occurs in a Dicer-independent, PIWI-Slicer-dependent manner. However, primary piRNA processing remains elusive. Here we analysed piRNA processing in a Drosophila ovarian somatic cell line where Piwi, but not Aub or AGO3, is expressed; thus, only the primary piRNAs exist. In addition to flamenco, a Piwi-specific piRNA cluster, traffic jam (tj), a large Maf gene, was determined as a new piRNA cluster. piRNAs arising from tj correspond to the untranslated regions of tj messenger RNA and are sense-oriented. piRNA loading on to Piwi may occur in the cytoplasm. zucchini, a gene encoding a putative cytoplasmic nuclease, is required for tj-derived piRNA production. In tj and piwi mutant ovaries, somatic cells fail to intermingle with germ cells and Fasciclin III is overexpressed. Loss of tj abolishes Piwi expression in gonadal somatic cells. Thus, in gonadal somatic cells, tj gives rise simultaneously to two different molecules: the TJ protein, which activates Piwi expression, and piRNAs, which define the Piwi targets for silencing.

  15. Dynamic interplay among homeostatic, hedonic, and cognitive feedback circuits regulating body weight.

    Science.gov (United States)

    Hall, Kevin D; Hammond, Ross A; Rahmandad, Hazhir

    2014-07-01

    Obesity is associated with a prolonged imbalance between energy intake and expenditure, both of which are regulated by multiple feedback processes within and across individuals. These processes constitute 3 hierarchical control systems-homeostatic, hedonic, and cognitive-with extensive interaction among them. Understanding complex eating behavior requires consideration of all 3 systems and their interactions. Existing models of these processes are widely scattered, with relatively few attempts to integrate across mechanisms. We briefly review available empirical evidence and dynamic models, discussing challenges and potential for better integration. We conclude that developing richer models of dynamic interplay among systems should be a priority in the future study of obesity and that systems science modeling offers the potential to aid in this goal.

  16. MOS integrated circuit design

    CERN Document Server

    Wolfendale, E

    2013-01-01

    MOS Integral Circuit Design aims to help in the design of integrated circuits, especially large-scale ones, using MOS Technology through teaching of techniques, practical applications, and examples. The book covers topics such as design equation and process parameters; MOS static and dynamic circuits; logic design techniques, system partitioning, and layout techniques. Also featured are computer aids such as logic simulation and mask layout, as well as examples on simple MOS design. The text is recommended for electrical engineers who would like to know how to use MOS for integral circuit desi

  17. Characterization and modeling of intermittent locomotor dynamics in clock gene-deficient mice.

    Directory of Open Access Journals (Sweden)

    Toru Nakamura

    Full Text Available The scale-invariant and intermittent dynamics of animal behavior are attracting scientific interest. Recent findings concerning the statistical laws of behavioral organization shared between healthy humans and wild-type mice (WT and their alterations in human depression patients and circadian clock gene (Period 2; Per2 mutant mice indicate that clock genes play functional roles in intermittent, ultradian locomotor dynamics. They also claim the clinical and biological importance of the laws as objective biobehavioral measures or endophenotypes for psychiatric disorders. In this study, to elucidate the roles of breakdown of the broader circadian regulatory circuit in intermittent behavioral dynamics, we studied the statistical properties and rhythmicity of locomotor activity in Per2 mutants and mice deficient in other clock genes (Bmal1, Clock. We performed wavelet analysis to examine circadian and ultradian rhythms and estimated the cumulative distributions of resting period durations during which locomotor activity levels are continuously lower than a predefined threshold value. The wavelet analysis revealed significant amplification of ultradian rhythms in the BMAL1-deficient mice, and instability in the Per2 mutants. The resting period distributions followed a power-law form in all mice. While the distributions for the BMAL1-deficient and Clock mutant mice were almost identical to those for the WT mice, with no significant differences in their parameter (power-law scaling exponent, only the Per2 mutant mice showed consistently and significantly lower values of the scaling exponent, indicating the increased intermittency in ultradian locomotor dynamics. Furthermore, based on a stochastic priority queuing model, we explained the power-law nature of resting period distributions, as well as its alterations shared with human depressive patients and Per2 mutant mice. Our findings lead to the development of a novel mathematical model for abnormal

  18. A Novel Chaotic System without Equilibrium: Dynamics, Synchronization, and Circuit Realization

    Directory of Open Access Journals (Sweden)

    Ahmad Taher Azar

    2017-01-01

    Full Text Available A few special chaotic systems without unstable equilibrium points have been investigated recently. It is worth noting that these special systems are different from normal chaotic ones because the classical Shilnikov criterion cannot be used to prove chaos of such systems. A novel unusual chaotic system without equilibrium is proposed in this work. We discover dynamical properties as well as the synchronization of the new system. Furthermore, a physical realization of the system without equilibrium is also implemented to illustrate its feasibility.

  19. Algebraic circuits

    CERN Document Server

    Lloris Ruiz, Antonio; Parrilla Roure, Luis; García Ríos, Antonio

    2014-01-01

    This book presents a complete and accurate study of algebraic circuits, digital circuits whose performance can be associated with any algebraic structure. The authors distinguish between basic algebraic circuits, such as Linear Feedback Shift Registers (LFSRs) and cellular automata, and algebraic circuits, such as finite fields or Galois fields. The book includes a comprehensive review of representation systems, of arithmetic circuits implementing basic and more complex operations, and of the residue number systems (RNS). It presents a study of basic algebraic circuits such as LFSRs and cellular automata as well as a study of circuits related to Galois fields, including two real cryptographic applications of Galois fields.

  20. Transcription dynamics of inducible genes modulated by negative regulations.

    Science.gov (United States)

    Li, Yanyan; Tang, Moxun; Yu, Jianshe

    2015-06-01

    Gene transcription is a stochastic process in single cells, in which genes transit randomly between active and inactive states. Transcription of many inducible genes is also tightly regulated: It is often stimulated by extracellular signals, activated through signal transduction pathways and later repressed by negative regulations. In this work, we study the nonlinear dynamics of the mean transcription level of inducible genes modulated by the interplay of the intrinsic transcriptional randomness and the repression by negative regulations. In our model, we integrate negative regulations into gene activation process, and make the conventional assumption on the production and degradation of transcripts. We show that, whether or not the basal transcription is temporarily terminated when cells are stimulated, the mean transcription level grows in the typical up and down pattern commonly observed in immune response genes. With the help of numerical simulations, we clarify the delicate impact of the system parameters on the transcription dynamics, and demonstrate how our model generates the distinct temporal gene-induction patterns in mouse fibroblasts discerned in recent experiments.

  1. Statistics of voltage drop in distribution circuits: a dynamic programming approach

    Energy Technology Data Exchange (ETDEWEB)

    Turitsyn, Konstantin S [Los Alamos National Laboratory

    2010-01-01

    We analyze a power distribution line with high penetration of distributed generation and strong variations of power consumption and generation levels. In the presence of uncertainty the statistical description of the system is required to assess the risks of power outages. In order to find the probability of exceeding the constraints for voltage levels we introduce the probability distribution of maximal voltage drop and propose an algorithm for finding this distribution. The algorithm is based on the assumption of random but statistically independent distribution of loads on buses. Linear complexity in the number of buses is achieved through the dynamic programming technique. We illustrate the performance of the algorithm by analyzing a simple 4-bus system with high variations of load levels.

  2. Precise regulation of gene expression dynamics favors complex promoter architectures.

    Directory of Open Access Journals (Sweden)

    Dirk Müller

    2009-01-01

    Full Text Available Promoters process signals through recruitment of transcription factors and RNA polymerase, and dynamic changes in promoter activity constitute a major noise source in gene expression. However, it is barely understood how complex promoter architectures determine key features of promoter dynamics. Here, we employ prototypical promoters of yeast ribosomal protein genes as well as simplified versions thereof to analyze the relations among promoter design, complexity, and function. These promoters combine the action of a general regulatory factor with that of specific transcription factors, a common motif of many eukaryotic promoters. By comprehensively analyzing stationary and dynamic promoter properties, this model-based approach enables us to pinpoint the structural characteristics underlying the observed behavior. Functional tradeoffs impose constraints on the promoter architecture of ribosomal protein genes. We find that a stable scaffold in the natural design results in low transcriptional noise and strong co-regulation of target genes in the presence of gene silencing. This configuration also exhibits superior shut-off properties, and it can serve as a tunable switch in living cells. Model validation with independent experimental data suggests that the models are sufficiently realistic. When combined, our results offer a mechanistic explanation for why specific factors are associated with low protein noise in vivo. Many of these findings hold for a broad range of model parameters and likely apply to other eukaryotic promoters of similar structure.

  3. A novel large signal and dynamic characterization to parameter a novel large signal and dynamic circuit model of a PEM fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Turpin, C.; Fontes, G.; Astier, S.; Arregui, M.G.; Phlippoteau, V. [LAPLACE - Laboratory Plasmas and Energy Conversion, Toulouse (France)

    2007-07-01

    An innovative large signal and dynamic circuit model of a proton exchange membrane (PEM) fuel cell was presented. It was developed from a generic approach that considers the energy exchange and the energy coupling within a fuel cell. This new model can be used to characterize a PEM fuel cell by exciting it with low frequency current sweeps whose amplitudes are high. It can be used for PEM fuel cells having activation; an electrochemical double layer; gas diffusion through the gas diffusion layer and the active layer; and ohmic losses. The proposed model is based on the theory of converting chemical energy into electrical energy, which is modelled by a voltage source. The activation phenomena and the gas diffusion phenomena are modeled by a current source in parallel with a capacity. The current source is piloted by the voltage which varies dynamically because of the associated capacitor. This paper describes the modelling steps in detail. It also proposed a parameter extraction method through experiments performed with a commercial PEMFC stack. It was concluded that both electrochemists and electrical engineers will be interested in this newly developed and validated model. 6 refs., 2 tabs., 8 figs.

  4. Inferring slowly-changing dynamic gene-regulatory networks.

    Science.gov (United States)

    Wit, Ernst C; Abbruzzo, Antonino

    2015-01-01

    Dynamic gene-regulatory networks are complex since the interaction patterns between their components mean that it is impossible to study parts of the network in separation. This holistic character of gene-regulatory networks poses a real challenge to any type of modelling. Graphical models are a class of models that connect the network with a conditional independence relationships between random variables. By interpreting these random variables as gene activities and the conditional independence relationships as functional non-relatedness, graphical models have been used to describe gene-regulatory networks. Whereas the literature has been focused on static networks, most time-course experiments are designed in order to tease out temporal changes in the underlying network. It is typically reasonable to assume that changes in genomic networks are few, because biological systems tend to be stable. We introduce a new model for estimating slow changes in dynamic gene-regulatory networks, which is suitable for high-dimensional data, e.g. time-course microarray data. Our aim is to estimate a dynamically changing genomic network based on temporal activity measurements of the genes in the network. Our method is based on the penalized likelihood with l1-norm, that penalizes conditional dependencies between genes as well as differences between conditional independence elements across time points. We also present a heuristic search strategy to find optimal tuning parameters. We re-write the penalized maximum likelihood problem into a standard convex optimization problem subject to linear equality constraints. We show that our method performs well in simulation studies. Finally, we apply the proposed model to a time-course T-cell dataset.

  5. A novel approach for electrical circuit modeling of Li-ion battery for predicting the steady-state and dynamic I–V characteristics

    Indian Academy of Sciences (India)

    SAURABH SAXENA; S RAGHU RAMAN; B SARITHA; VINOD JOHN

    2016-05-01

    A novel approach for electrical circuit modeling of Li-ion battery is proposed in this paper. The model proposed in this paper is simple, fast, not memory intensive and does not involve any look-up table. The model mimics the steady-state and dynamic behavior of battery. Internal charge distribution of the battery is modeled using two RC circuits. Self-discharge characteristic of the battery is modeled using a leakage resistance. Experimental procedure to determine the internal resistance, leakage resistance and the value of RC elements is explained in detail. The variation of parameters with state of charge (SOC) and magnitude of current is presented. The internal voltage source of the battery model varies dynamically with SOC to replicate the experimental terminal voltage characteristics of battery. The accuracy of model is validated with experimental results.

  6. Dynamic association rules for gene expression data analysis.

    Science.gov (United States)

    Chen, Shu-Chuan; Tsai, Tsung-Hsien; Chung, Cheng-Han; Li, Wen-Hsiung

    2015-10-14

    The purpose of gene expression analysis is to look for the association between regulation of gene expression levels and phenotypic variations. This association based on gene expression profile has been used to determine whether the induction/repression of genes correspond to phenotypic variations including cell regulations, clinical diagnoses and drug development. Statistical analyses on microarray data have been developed to resolve gene selection issue. However, these methods do not inform us of causality between genes and phenotypes. In this paper, we propose the dynamic association rule algorithm (DAR algorithm) which helps ones to efficiently select a subset of significant genes for subsequent analysis. The DAR algorithm is based on association rules from market basket analysis in marketing. We first propose a statistical way, based on constructing a one-sided confidence interval and hypothesis testing, to determine if an association rule is meaningful. Based on the proposed statistical method, we then developed the DAR algorithm for gene expression data analysis. The method was applied to analyze four microarray datasets and one Next Generation Sequencing (NGS) dataset: the Mice Apo A1 dataset, the whole genome expression dataset of mouse embryonic stem cells, expression profiling of the bone marrow of Leukemia patients, Microarray Quality Control (MAQC) data set and the RNA-seq dataset of a mouse genomic imprinting study. A comparison of the proposed method with the t-test on the expression profiling of the bone marrow of Leukemia patients was conducted. We developed a statistical way, based on the concept of confidence interval, to determine the minimum support and minimum confidence for mining association relationships among items. With the minimum support and minimum confidence, one can find significant rules in one single step. The DAR algorithm was then developed for gene expression data analysis. Four gene expression datasets showed that the proposed

  7. 立体组装电路模块动态特性的有限元模拟与分析%Simulation and Analysis of Dynamic Characteristics of 3D Assembly Circuit Module with Finite Element Method

    Institute of Scientific and Technical Information of China (English)

    黄春跃; 周德俭; 黄红艳

    2004-01-01

    Based on the modal analysis theory and by using the dynamics finite element analysis model of a three-dimensional assembly circuit module, dynamic characteristics of circuit module have been studied, including both natural characteristics analysis and dynamic responses analysis. Using a subspace method, modal analysis is first carried out. The first 6 orders of natural frequencies and vibration modes are obtained. Influence of the number of the Z-shaped metal slices on dynamic characteristics of the entire structure is also studied.Harmonic response analysis is then conducted. The steady-state response when the circuit module is subjected to harmonic excitation is determined. A curve of the response values against frequencies is obtained. As a result, the optimal number of Z-shaped metal slices can be determined, and it can be assured that the three-dimensional assembly circuit module has good performance in terms of the dynamic characteristics.

  8. Dynamic regulation of cerebral DNA repair genes by psychological stress

    DEFF Research Database (Denmark)

    Forsberg, Kristin; Aalling, Nadia; Wörtwein, Gitta

    2015-01-01

    for maintaining genomic integrity. The aim of the present study was to characterize the pattern of cerebral DNA repair enzyme regulation after stress through the quantification of a targeted range of gene products involved in different types of DNA repair. 72 male Sprague-Dawley rats were subjected to either...... was seen in HC, but with overall smaller effects and without the induction after acute stress. Nuclear DNA damage from oxidation as measured by the comet assay was unaffected by stress in both regions. We conclude that psychological stress have a dynamic influence on brain DNA repair gene expression...

  9. Design and Implementation of Visual Dynamic Display Software of Gene Expression Based on GTK

    Institute of Scientific and Technical Information of China (English)

    JIANG Wei; MENG Fanjiang; LI Yong; YU Xiao

    2009-01-01

    The paper presented an implement method for a dynamic gene expression display software based on the GTK. This method established the dynamic presentation system of gene expression which according to gene expression data from gene chip hybridize at different time, adopted a linearity combination model and Pearson correlation coefficient algorithm. The system described the gene expression changes in graphic form, the gene expression changes with time and the changes in characteristics of the gene expression, also the changes in relations of the gene expression and regulation relationships among genes. The system also provided an integrated platform for analysis on gene chips data, especially for the research on the network of gene regulation.

  10. Defining the robust behaviour of the plant clock gene circuit with absolute RNA timeseries and open infrastructure.

    Science.gov (United States)

    Flis, Anna; Fernández, Aurora Piñas; Zielinski, Tomasz; Mengin, Virginie; Sulpice, Ronan; Stratford, Kevin; Hume, Alastair; Pokhilko, Alexandra; Southern, Megan M; Seaton, Daniel D; McWatters, Harriet G; Stitt, Mark; Halliday, Karen J; Millar, Andrew J

    2015-10-01

    Our understanding of the complex, transcriptional feedback loops in the circadian clock mechanism has depended upon quantitative, timeseries data from disparate sources. We measure clock gene RNA profiles in Arabidopsis thaliana seedlings, grown with or without exogenous sucrose, or in soil-grown plants and in wild-type and mutant backgrounds. The RNA profiles were strikingly robust across the experimental conditions, so current mathematical models are likely to be broadly applicable in leaf tissue. In addition to providing reference data, unexpected behaviours included co-expression of PRR9 and ELF4, and regulation of PRR5 by GI. Absolute RNA quantification revealed low levels of PRR9 transcripts (peak approx. 50 copies cell(-1)) compared with other clock genes, and threefold higher levels of LHY RNA (more than 1500 copies cell(-1)) than of its close relative CCA1. The data are disseminated from BioDare, an online repository for focused timeseries data, which is expected to benefit mechanistic modelling. One data subset successfully constrained clock gene expression in a complex model, using publicly available software on parallel computers, without expert tuning or programming. We outline the empirical and mathematical justification for data aggregation in understanding highly interconnected, dynamic networks such as the clock, and the observed design constraints on the resources required to make this approach widely accessible. © 2015 The Authors.

  11. Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation

    Science.gov (United States)

    Goode, Debbie K.; Obier, Nadine; Vijayabaskar, M.S.; Lie-A-Ling, Michael; Lilly, Andrew J.; Hannah, Rebecca; Lichtinger, Monika; Batta, Kiran; Florkowska, Magdalena; Patel, Rahima; Challinor, Mairi; Wallace, Kirstie; Gilmour, Jane; Assi, Salam A.; Cauchy, Pierre; Hoogenkamp, Maarten; Westhead, David R.; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold; Bonifer, Constanze

    2016-01-01

    Summary Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development. PMID:26923725

  12. Gallium Arsenide Domino Circuit

    Science.gov (United States)

    Yang, Long; Long, Stephen I.

    1990-01-01

    Advantages include reduced power and high speed. Experimental gallium arsenide field-effect-transistor (FET) domino circuit replicated in large numbers for use in dynamic-logic systems. Name of circuit denotes mode of operation, which logic signals propagate from each stage to next when successive stages operated at slightly staggered clock cycles, in manner reminiscent of dominoes falling in a row. Building block of domino circuit includes input, inverter, and level-shifting substages. Combinational logic executed in input substage. During low half of clock cycle, result of logic operation transmitted to following stage.

  13. Structures and Boolean Dynamics in Gene Regulatory Networks

    Science.gov (United States)

    Szedlak, Anthony

    This dissertation discusses the topological and dynamical properties of GRNs in cancer, and is divided into four main chapters. First, the basic tools of modern complex network theory are introduced. These traditional tools as well as those developed by myself (set efficiency, interset efficiency, and nested communities) are crucial for understanding the intricate topological properties of GRNs, and later chapters recall these concepts. Second, the biology of gene regulation is discussed, and a method for disease-specific GRN reconstruction developed by our collaboration is presented. This complements the traditional exhaustive experimental approach of building GRNs edge-by-edge by quickly inferring the existence of as of yet undiscovered edges using correlations across sets of gene expression data. This method also provides insight into the distribution of common mutations across GRNs. Third, I demonstrate that the structures present in these reconstructed networks are strongly related to the evolutionary histories of their constituent genes. Investigation of how the forces of evolution shaped the topology of GRNs in multicellular organisms by growing outward from a core of ancient, conserved genes can shed light upon the ''reverse evolution'' of normal cells into unicellular-like cancer states. Next, I simulate the dynamics of the GRNs of cancer cells using the Hopfield model, an infinite range spin-glass model designed with the ability to encode Boolean data as attractor states. This attractor-driven approach facilitates the integration of gene expression data into predictive mathematical models. Perturbations representing therapeutic interventions are applied to sets of genes, and the resulting deviations from their attractor states are recorded, suggesting new potential drug targets for experimentation. Finally, I extend the Hopfield model to modular networks, cyclic attractors, and complex attractors, and apply these concepts to simulations of the cell cycle

  14. Negative circuits and sustained oscillations in asynchronous automata networks

    CERN Document Server

    Richard, Adrien

    2009-01-01

    The biologist Ren\\'e Thomas conjectured, twenty years ago, that the presence of a negative feedback circuit in the interaction graph of a dynamical system is a necessary condition for this system to produce sustained oscillations. In this paper, we state and prove this conjecture for asynchronous automata networks, a class of discrete dynamical systems extensively used to model the behaviors of gene networks. As a corollary, we obtain the following fixed point theorem: given a product $X$ of $n$ finite intervals of integers, and a map $F$ from $X$ to itself, if the interaction graph associated with $F$ has no negative circuit, then $F$ has at least one fixed point.

  15. Effects of transcriptional pausing on gene expression dynamics.

    Directory of Open Access Journals (Sweden)

    Tiina Rajala

    2010-03-01

    Full Text Available Stochasticity in gene expression affects many cellular processes and is a source of phenotypic diversity between genetically identical individuals. Events in elongation, particularly RNA polymerase pausing, are a source of this noise. Since the rate and duration of pausing are sequence-dependent, this regulatory mechanism of transcriptional dynamics is evolvable. The dependency of pause propensity on regulatory molecules makes pausing a response mechanism to external stress. Using a delayed stochastic model of bacterial transcription at the single nucleotide level that includes the promoter open complex formation, pausing, arrest, misincorporation and editing, pyrophosphorolysis, and premature termination, we investigate how RNA polymerase pausing affects a gene's transcriptional dynamics and gene networks. We show that pauses' duration and rate of occurrence affect the bursting in RNA production, transcriptional and translational noise, and the transient to reach mean RNA and protein levels. In a genetic repressilator, increasing the pausing rate and the duration of pausing events increases the period length but does not affect the robustness of the periodicity. We conclude that RNA polymerase pausing might be an important evolvable feature of genetic networks.

  16. Recombination dynamics as a key determinant of open circuit voltage in organic bulk heterojunction solar cells: a comparison of four different donor polymers

    Energy Technology Data Exchange (ETDEWEB)

    Maurano, Andrea; Hamilton, Rick; Shuttle, Chris G.; O' Regan, Brian; Zhang, Weimin; McCulloch, Iain; Durrant, James R. [Departments of Chemistry, Imperial College London, South Kensington SW7 2AZ (United Kingdom); Ballantyne, Amy M.; Nelson, Jenny [Departments of Physics, Imperial College London, South Kensington SW7 2AZ (United Kingdom); Azimi, Hamed [Konarka Austria, Altenbergerstrasse 69, A-4040 Linz (Austria); Christian Doppler Laboratory for Surface Optics, Johannes Kepler University, Linz (Austria); Morana, Mauro; Brabec, Christoph J. [Konarka Austria, Altenbergerstrasse 69, A-4040 Linz (Austria)

    2010-11-24

    Transient photovoltage and charge extraction analyses are employed to analyzes charge carrier densities and bimolecular recombination dynamics in organic polymer: fullerene solar cells under open circuit operating conditions, employing four different donor polymers. An equation is derived which allows us to calculate the device V{sub OC} from these kinetic measurements. This equation allows us to calculate voltage output of devices within {+-} 25 meV of directly measured values. This analysis thus allows us to relate device open circuit voltage directly to the kinetics of bimolecular recombination, and thereby the influence of nanomorphology upon device voltage output. (Copyright copyright 2010 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  17. Robust dynamic balance of AP-1 transcription factors in a neuronal gene regulatory network

    Directory of Open Access Journals (Sweden)

    Schwaber James S

    2010-12-01

    Full Text Available Abstract Background The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS, which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of hypertension, are not understood. Results We developed and analyzed a mathematical model of AT1R-activated signaling kinases and a downstream gene regulatory network, with structural basis in our transcriptomic data analysis and literature. To our knowledge, our report presents the first computational model of this key regulatory network. Our simulations and analysis reveal a dynamic balance among distinct dimers of the AP-1 family of transcription factors. We investigated the robustness of this behavior to simultaneous perturbations in the network parameters using a novel multivariate approach that integrates global sensitivity analysis with decision-tree methods. Our analysis implicates a subset of Fos and Jun dependent mechanisms, with dynamic sensitivities shifting from Fos-regulating kinase (FRK-mediated processes to those downstream of c-Jun N-terminal kinase (JNK. Decision-tree analysis indicated that while there may be a large combinatorial functional space feasible for neuronal states and parameters, the network behavior is constrained to a small set of AP-1 response profiles. Many of the paths through the combinatorial parameter space lead to a dynamic balance of AP-1 dimer forms, yielding a robust AP-1 response counteracting the biological variability. Conclusions Based on the simulation

  18. Lateral Gene Transfer Dynamics in the Ancient Bacterial Genus Streptomyces.

    Science.gov (United States)

    McDonald, Bradon R; Currie, Cameron R

    2017-06-06

    Lateral gene transfer (LGT) profoundly shapes the evolution of bacterial lineages. LGT across disparate phylogenetic groups and genome content diversity between related organisms suggest a model of bacterial evolution that views LGT as rampant and promiscuous. It has even driven the argument that species concepts and tree-based phylogenetics cannot be applied to bacteria. Here, we show that acquisition and retention of genes through LGT are surprisingly rare in the ubiquitous and biomedically important bacterial genus Streptomyces Using a molecular clock, we estimate that the Streptomyces bacteria are ~380 million years old, indicating that this bacterial genus is as ancient as land vertebrates. Calibrating LGT rate to this geologic time span, we find that on average only 10 genes per million years were acquired and subsequently maintained. Over that same time span, Streptomyces accumulated thousands of point mutations. By explicitly incorporating evolutionary timescale into our analyses, we provide a dramatically different view on the dynamics of LGT and its impact on bacterial evolution.IMPORTANCE Tree-based phylogenetics and the use of species as units of diversity lie at the foundation of modern biology. In bacteria, these pillars of evolutionary theory have been called into question due to the observation of thousands of lateral gene transfer (LGT) events within and between lineages. Here, we show that acquisition and retention of genes through LGT are exceedingly rare in the bacterial genus Streptomyces, with merely one gene acquired in Streptomyces lineages every 100,000 years. These findings stand in contrast to the current assumption of rampant genetic exchange, which has become the dominant hypothesis used to explain bacterial diversity. Our results support a more nuanced understanding of genetic exchange, with LGT impacting evolution over short timescales but playing a significant role over long timescales. Deeper understanding of LGT provides new

  19. Dynamic feedback circuits function as a switch for shaping a maturation-inducing steroid pulse in Drosophila

    DEFF Research Database (Denmark)

    Møller, Morten Erik; Danielsen, Erik Thomas; Herder, Rachel;

    2013-01-01

    Steroid hormones trigger the onset of sexual maturation in animals by initiating genetic response programs that are determined by steroid pulse frequency, amplitude and duration. Although steroid pulses coordinate growth and timing of maturation during development, the mechanisms generating...... that functions in producing steroid oscillations that can guide the decision to terminate growth and promote maturation....... these pulses are not known. Here we show that the ecdysone steroid pulse that drives the juvenile-adult transition in Drosophila is determined by feedback circuits in the prothoracic gland (PG), the major steroid-producing tissue of insect larvae. These circuits coordinate the activation and repression...

  20. Selective Manipulation of Neural Circuits.

    Science.gov (United States)

    Park, Hong Geun; Carmel, Jason B

    2016-04-01

    Unraveling the complex network of neural circuits that form the nervous system demands tools that can manipulate specific circuits. The recent evolution of genetic tools to target neural circuits allows an unprecedented precision in elucidating their function. Here we describe two general approaches for achieving circuit specificity. The first uses the genetic identity of a cell, such as a transcription factor unique to a circuit, to drive expression of a molecule that can manipulate cell function. The second uses the spatial connectivity of a circuit to achieve specificity: one genetic element is introduced at the origin of a circuit and the other at its termination. When the two genetic elements combine within a neuron, they can alter its function. These two general approaches can be combined to allow manipulation of neurons with a specific genetic identity by introducing a regulatory gene into the origin or termination of the circuit. We consider the advantages and disadvantages of both these general approaches with regard to specificity and efficacy of the manipulations. We also review the genetic techniques that allow gain- and loss-of-function within specific neural circuits. These approaches introduce light-sensitive channels (optogenetic) or drug sensitive channels (chemogenetic) into neurons that form specific circuits. We compare these tools with others developed for circuit-specific manipulation and describe the advantages of each. Finally, we discuss how these tools might be applied for identification of the neural circuits that mediate behavior and for repair of neural connections.

  1. MAGIA2: from miRNA and genes expression data integrative analysis to microRNA–transcription factor mixed regulatory circuits (2012 update)

    Science.gov (United States)

    Bisognin, Andrea; Sales, Gabriele; Coppe, Alessandro; Bortoluzzi, Stefania; Romualdi, Chiara

    2012-01-01

    MAGIA2 (http://gencomp.bio.unipd.it/magia2) is an update, extension and evolution of the MAGIA web tool. It is dedicated to the integrated analysis of in silico target prediction, microRNA (miRNA) and gene expression data for the reconstruction of post-transcriptional regulatory networks. miRNAs are fundamental post-transcriptional regulators of several key biological and pathological processes. As miRNAs act prevalently through target degradation, their expression profiles are expected to be inversely correlated to those of the target genes. Low specificity of target prediction algorithms makes integration approaches an interesting solution for target prediction refinement. MAGIA2 performs this integrative approach supporting different association measures, multiple organisms and almost all target predictions algorithms. Nevertheless, miRNAs activity should be viewed as part of a more complex scenario where regulatory elements and their interactors generate a highly connected network and where gene expression profiles are the result of different levels of regulation. The updated MAGIA2 tries to dissect this complexity by reconstructing mixed regulatory circuits involving either miRNA or transcription factor (TF) as regulators. Two types of circuits are identified: (i) a TF that regulates both a miRNA and its target and (ii) a miRNA that regulates both a TF and its target. PMID:22618880

  2. MAGIA²: from miRNA and genes expression data integrative analysis to microRNA-transcription factor mixed regulatory circuits (2012 update).

    Science.gov (United States)

    Bisognin, Andrea; Sales, Gabriele; Coppe, Alessandro; Bortoluzzi, Stefania; Romualdi, Chiara

    2012-07-01

    MAGIA(2) (http://gencomp.bio.unipd.it/magia2) is an update, extension and evolution of the MAGIA web tool. It is dedicated to the integrated analysis of in silico target prediction, microRNA (miRNA) and gene expression data for the reconstruction of post-transcriptional regulatory networks. miRNAs are fundamental post-transcriptional regulators of several key biological and pathological processes. As miRNAs act prevalently through target degradation, their expression profiles are expected to be inversely correlated to those of the target genes. Low specificity of target prediction algorithms makes integration approaches an interesting solution for target prediction refinement. MAGIA(2) performs this integrative approach supporting different association measures, multiple organisms and almost all target predictions algorithms. Nevertheless, miRNAs activity should be viewed as part of a more complex scenario where regulatory elements and their interactors generate a highly connected network and where gene expression profiles are the result of different levels of regulation. The updated MAGIA(2) tries to dissect this complexity by reconstructing mixed regulatory circuits involving either miRNA or transcription factor (TF) as regulators. Two types of circuits are identified: (i) a TF that regulates both a miRNA and its target and (ii) a miRNA that regulates both a TF and its target.

  3. Resonance circuits for adiabatic circuits

    Directory of Open Access Journals (Sweden)

    C. Schlachta

    2003-01-01

    Full Text Available One of the possible techniques to reduces the power consumption in digital CMOS circuits is to slow down the charge transport. This slowdown can be achieved by introducing an inductor in the charging path. Additionally, the inductor can act as an energy storage element, conserving the energy that is normally dissipated during discharging. Together with the parasitic capacitances from the circuit a LCresonant circuit is formed.

  4. Study of the interrelation between the electrotechnical parameters of the plasma focus discharge circuit and the plasma compression dynamics on the PF-3 and PF-1000 facilities

    Energy Technology Data Exchange (ETDEWEB)

    Mitrofanov, K. N., E-mail: mitrkn@inbox.ru [Troitsk Institute for Innovation and Fusion Research (Russian Federation); Krauz, V. I., E-mail: krauz-vi@nrcki.ru, E-mail: vkrauz@yandex.ru [National Research Centre Kurchatov Institute (Russian Federation); Grabovski, E. V. [Troitsk Institute for Innovation and Fusion Research (Russian Federation); Myalton, V. V.; Vinogradov, V. P. [National Research Centre Kurchatov Institute (Russian Federation); Paduch, M. [Institute of Plasma Physics and Laser Microfusion (Poland); Scholz, M. [Polish Academy of Sciences, Niewodniczański Institute of Nuclear Physics (Poland); Karpiński, L. [Łukasiewicz University of Technology, Faculty of Electrical and Computer Engineering (Poland)

    2015-05-15

    The main stages of the plasma current sheath (PCS) dynamics on two plasma focus (PF) facilities with different geometries of the electrode system, PF-3 (Filippov type) and PF-1000 (Mather type), were studied by analyzing the results of the current and voltage measurements. Some dynamic characteristics, such as the PCS velocity in the acceleration phase in the Mather-type facility (PF-1000), the moment at which the PCS reaches the anode end, and the plasma velocity in the radial stage of plasma compression in the PF-3 Filippov-type facility, were determined from the time dependence of the inductance of the discharge circuit with a dynamic plasma load. The energy characteristics of the discharge circuit of the compressing PCS were studied for different working gases (deuterium, argon, and neon) at initial pressures of 1.5–3 Torr in discharges with energies of 0.3–0.6 MJ. In experiments with deuterium, correlation between the neutron yield and the electromagnetic energy deposited directly in the compressed PCS was investigated.

  5. A Minimal Model of Ribosome Allocation Dynamics Captures Trade-offs in Expression between Endogenous and Synthetic Genes.

    Science.gov (United States)

    Gorochowski, Thomas E; Avcilar-Kucukgoze, Irem; Bovenberg, Roel A L; Roubos, Johannes A; Ignatova, Zoya

    2016-07-15

    Cells contain a finite set of resources that must be distributed across many processes to ensure survival. Among them, the largest proportion of cellular resources is dedicated to protein translation. Synthetic biology often exploits these resources in executing orthogonal genetic circuits, yet the burden this places on the cell is rarely considered. Here, we develop a minimal model of ribosome allocation dynamics capturing the demands on translation when expressing a synthetic construct together with endogenous genes required for the maintenance of cell physiology. Critically, it contains three key variables related to design parameters of the synthetic construct covering transcript abundance, translation initiation rate, and elongation time. We show that model-predicted changes in ribosome allocation closely match experimental shifts in synthetic protein expression rate and cellular growth. Intriguingly, the model is also able to accurately infer transcript levels and translation times after further exposure to additional ambient stress. Our results demonstrate that a simple model of resource allocation faithfully captures the redistribution of protein synthesis resources when faced with the burden of synthetic gene expression and environmental stress. The tractable nature of the model makes it a versatile tool for exploring the guiding principles of efficient heterologous expression and the indirect interactions that can arise between synthetic circuits and their host chassis because of competition for shared translational resources.

  6. Global Analysis of miRNA Gene Clusters and Gene Families Reveals Dynamic and Coordinated Expression

    Directory of Open Access Journals (Sweden)

    Li Guo

    2014-01-01

    Full Text Available To further understand the potential expression relationships of miRNAs in miRNA gene clusters and gene families, a global analysis was performed in 4 paired tumor (breast cancer and adjacent normal tissue samples using deep sequencing datasets. The compositions of miRNA gene clusters and families are not random, and clustered and homologous miRNAs may have close relationships with overlapped miRNA species. Members in the miRNA group always had various expression levels, and even some showed larger expression divergence. Despite the dynamic expression as well as individual difference, these miRNAs always indicated consistent or similar deregulation patterns. The consistent deregulation expression may contribute to dynamic and coordinated interaction between different miRNAs in regulatory network. Further, we found that those clustered or homologous miRNAs that were also identified as sense and antisense miRNAs showed larger expression divergence. miRNA gene clusters and families indicated important biological roles, and the specific distribution and expression further enrich and ensure the flexible and robust regulatory network.

  7. Electronic circuit analog of synthetic genetic networks: Revisited

    Science.gov (United States)

    Hellen, Edward H.; Kurths, Jürgen; Dana, Syamal K.

    2017-06-01

    Electronic circuits are useful tools for studying potential dynamical behaviors of synthetic genetic networks. The circuit models are complementary to numerical simulations of the networks, especially providing a framework for verification of dynamical behaviors in the presence of intrinsic and extrinsic noise of the electrical systems. Here we present an improved version of our previous design of an electronic analog of genetic networks that includes the 3-gene Repressilator and we show conversions between model parameters and real circuit component values to mimic the numerical results in experiments. Important features of the circuit design include the incorporation of chemical kinetics representing Hill function inhibition, quorum sensing coupling, and additive noise. Especially, we make a circuit design for a systematic change of initial conditions in experiment, which is critically important for studies of dynamical systems' behavior, particularly, when it shows multistability. This improved electronic analog of the synthetic genetic network allows us to extend our investigations from an isolated Repressilator to coupled Repressilators and to reveal the dynamical behavior's complexity.

  8. Ancestral regulatory circuits governing ectoderm patterning downstream of Nodal and BMP2/4 revealed by gene regulatory network analysis in an echinoderm.

    Directory of Open Access Journals (Sweden)

    Alexandra Saudemont

    Full Text Available Echinoderms, which are phylogenetically related to vertebrates and produce large numbers of transparent embryos that can be experimentally manipulated, offer many advantages for the analysis of the gene regulatory networks (GRN regulating germ layer formation. During development of the sea urchin embryo, the ectoderm is the source of signals that pattern all three germ layers along the dorsal-ventral axis. How this signaling center controls patterning and morphogenesis of the embryo is not understood. Here, we report a large-scale analysis of the GRN deployed in response to the activity of this signaling center in the embryos of the Mediterranean sea urchin Paracentrotus lividus, in which studies with high spatial resolution are possible. By using a combination of in situ hybridization screening, overexpression of mRNA, recombinant ligand treatments, and morpholino-based loss-of-function studies, we identified a cohort of transcription factors and signaling molecules expressed in the ventral ectoderm, dorsal ectoderm, and interposed neurogenic ("ciliary band" region in response to the known key signaling molecules Nodal and BMP2/4 and defined the epistatic relationships between the most important genes. The resultant GRN showed a number of striking features. First, Nodal was found to be essential for the expression of all ventral and dorsal marker genes, and BMP2/4 for all dorsal genes. Second, goosecoid was identified as a central player in a regulatory sub-circuit controlling mouth formation, while tbx2/3 emerged as a critical factor for differentiation of the dorsal ectoderm. Finally, and unexpectedly, a neurogenic ectoderm regulatory circuit characterized by expression of "ciliary band" genes was triggered in the absence of TGF beta signaling. We propose a novel model for ectoderm regionalization, in which neural ectoderm is the default fate in the absence of TGF beta signaling, and suggest that the stomodeal and neural subcircuits that we

  9. Preparation of Power Distribution System for High Penetration of Renewable Energy Part I. Dynamic Voltage Restorer for Voltage Regulation Pat II. Distribution Circuit Modeling and Validation

    Science.gov (United States)

    Khoshkbar Sadigh, Arash

    Part I: Dynamic Voltage Restorer In the present power grids, voltage sags are recognized as a serious threat and a frequently occurring power-quality problem and have costly consequence such as sensitive loads tripping and production loss. Consequently, the demand for high power quality and voltage stability becomes a pressing issue. Dynamic voltage restorer (DVR), as a custom power device, is more effective and direct solutions for "restoring" the quality of voltage at its load-side terminals when the quality of voltage at its source-side terminals is disturbed. In the first part of this thesis, a DVR configuration with no need of bulky dc link capacitor or energy storage is proposed. This fact causes to reduce the size of the DVR and increase the reliability of the circuit. In addition, the proposed DVR topology is based on high-frequency isolation transformer resulting in the size reduction of transformer. The proposed DVR circuit, which is suitable for both low- and medium-voltage applications, is based on dc-ac converters connected in series to split the main dc link between the inputs of dc-ac converters. This feature makes it possible to use modular dc-ac converters and utilize low-voltage components in these converters whenever it is required to use DVR in medium-voltage application. The proposed configuration is tested under different conditions of load power factor and grid voltage harmonic. It has been shown that proposed DVR can compensate the voltage sag effectively and protect the sensitive loads. Following the proposition of the DVR topology, a fundamental voltage amplitude detection method which is applicable in both single/three-phase systems for DVR applications is proposed. The advantages of proposed method include application in distorted power grid with no need of any low-pass filter, precise and reliable detection, simple computation and implementation without using a phased locked loop and lookup table. The proposed method has been verified

  10. Control of Vibrio fischeri lux gene transcription by a cyclic AMP receptor protein-luxR protein regulatory circuit.

    OpenAIRE

    1988-01-01

    Expression of the Vibrio fischeri luminescence genes (lux genes) requires two transcriptional activators: the V. fischeri luxR gene product with autoinducer and the cyclic AMP (cAMP) receptor protein (CRP) with cAMP. It has been established that autoinducer and the luxR gene product are required for transcriptional activation of the luxICDABE operon, which contains a gene required for autoinducer synthesis and genes required for light emission. However, the role of cAMP-CRP in the induction o...

  11. GATING CIRCUITS

    Science.gov (United States)

    Merrill, L.C.

    1958-10-14

    Control circuits for vacuum tubes are described, and a binary counter having an improved trigger circuit is reported. The salient feature of the binary counter is the application of the input signal to the cathode of each of two vacuum tubes through separate capacitors and the connection of each cathode to ground through separate diodes. The control of the binary counter is achieved in this manner without special pulse shaping of the input signal. A further advantage of the circuit is the simplicity and minimum nuruber of components required, making its use particularly desirable in computer machines.

  12. Out-of-equilibrium dynamics of gene expression and the Jarzynski equality.

    Science.gov (United States)

    Berg, Johannes

    2008-05-09

    In order to express specific genes at the right time, the transcription of genes is regulated by the presence and absence of transcription factor molecules. With transcription factor concentrations undergoing constant changes, gene transcription takes place out of equilibrium. In this Letter we discuss a simple mapping between dynamic models of gene expression and stochastic systems driven out of equilibrium. Using this mapping, results of out-of-equilibrium statistical mechanics such as the Jarzynski equality and the fluctuation theorem are demonstrated for gene expression dynamics. Applications of this approach include the determination of regulatory interactions between genes from experimental gene expression data.

  13. Dynamic feedback circuits function as a switch for shaping a maturation-inducing steroid pulse in Drosophila

    Science.gov (United States)

    Moeller, Morten E.; Danielsen, E. Thomas; Herder, Rachel; O’Connor, Michael B.; Rewitz, Kim F.

    2013-01-01

    Steroid hormones trigger the onset of sexual maturation in animals by initiating genetic response programs that are determined by steroid pulse frequency, amplitude and duration. Although steroid pulses coordinate growth and timing of maturation during development, the mechanisms generating these pulses are not known. Here we show that the ecdysone steroid pulse that drives the juvenile-adult transition in Drosophila is determined by feedback circuits in the prothoracic gland (PG), the major steroid-producing tissue of insect larvae. These circuits coordinate the activation and repression of hormone synthesis, the two key parameters determining pulse shape (amplitude and duration). We show that ecdysone has a positive-feedback effect on the PG, rapidly amplifying its own synthesis to trigger pupariation as the onset of maturation. During the prepupal stage, a negative-feedback signal ensures the decline in ecdysone levels required to produce a temporal steroid pulse that drives developmental progression to adulthood. The feedback circuits rely on a developmental switch in the expression of Broad isoforms that transcriptionally activate or silence components in the ecdysone biosynthetic pathway. Remarkably, our study shows that the same well-defined genetic program that stimulates a systemic downstream response to ecdysone is also utilized upstream to set the duration and amplitude of the ecdysone pulse. Activation of this switch-like mechanism ensures a rapid, self-limiting PG response that functions in producing steroid oscillations that can guide the decision to terminate growth and promote maturation. PMID:24173800

  14. Dynamics of coupled simplest chaotic two-component electronic circuits and its potential application to random bit generation

    Energy Technology Data Exchange (ETDEWEB)

    Modeste Nguimdo, Romain, E-mail: Romain.Nguimdo@vub.ac.be [Applied Physics Research Group, APHY, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussel (Belgium); Tchitnga, Robert [Laboratory of Electronics, Automation and Signal Processing, Department of Physics, University of Dschang, P.O. Box 67, Dschang (Cameroon); Woafo, Paul [Laboratory of Modelling and Simulation in Engineering and Biological Physics, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé (Cameroon)

    2013-12-15

    We numerically investigate the possibility of using a coupling to increase the complexity in simplest chaotic two-component electronic circuits operating at high frequency. We subsequently show that complex behaviors generated in such coupled systems, together with the post-processing are suitable for generating bit-streams which pass all the NIST tests for randomness. The electronic circuit is built up by unidirectionally coupling three two-component (one active and one passive) oscillators in a ring configuration through resistances. It turns out that, with such a coupling, high chaotic signals can be obtained. By extracting points at fixed interval of 10 ns (corresponding to a bit rate of 100 Mb/s) on such chaotic signals, each point being simultaneously converted in 16-bits (or 8-bits), we find that the binary sequence constructed by including the 10(or 2) least significant bits pass statistical tests of randomness, meaning that bit-streams with random properties can be achieved with an overall bit rate up to 10×100 Mb/s =1Gbit/s (or 2×100 Mb/s =200 Megabit/s). Moreover, by varying the bias voltages, we also investigate the parameter range for which more complex signals can be obtained. Besides being simple to implement, the two-component electronic circuit setup is very cheap as compared to optical and electro-optical systems.

  15. Dynamical Processes in Ageing, Gene Regulation and Communication

    DEFF Research Database (Denmark)

    Bendtsen, Kristian Moss

    project we constructed a mathematical model and showed that if DNA damage is primarily caused by geno-toxic agents, it would be advantageous for cells to have a fragile DNA repair mechanism. The second part of my Ph.D. thesis covers gene regulation. In the first project we show how RNA polymerase can...... be used as a transcription factor. This requires that promoter regions overlap, which 15% of promoters in E.coli do. In the second project I analyse a negative auto regulated transcription motif coupled to a positive auto regulation transcription motif. I find that a general feature of this motif...... players develop favourite communication partners. We observed how this dynamic caused a communication network to form. By quantifying the information flow in this network, we were able to shown how that the network functions as an anti-exploration mechanism against "information leeches"....

  16. Dynamic Post-Transcriptional Regulation of HIV-1 Gene Expression

    Science.gov (United States)

    Kula, Anna; Marcello, Alessandro

    2012-01-01

    Gene expression of the human immunodeficiency virus type 1 (HIV-1) is a highly regulated process. Basal transcription of the integrated provirus generates early transcripts that encode for the viral products Tat and Rev. Tat promotes the elongation of RNA polymerase while Rev mediates the nuclear export of viral RNAs that contain the Rev-responsive RNA element (RRE). These RNAs are exported from the nucleus to allow expression of Gag-Pol and Env proteins and for the production of full-length genomic RNAs. A balance exists between completely processed mRNAs and RRE-containing RNAs. Rev functions as an adaptor that recruits cellular factors to re-direct singly spliced and unspliced viral RNAs to nuclear export. The aim of this review is to address the dynamic regulation of this post-transcriptional pathway in light of recent findings that implicate several novel cellular cofactors of Rev function. PMID:24832221

  17. Dynamic Post-Transcriptional Regulation of HIV-1 Gene Expression

    Directory of Open Access Journals (Sweden)

    Alessandro Marcello

    2012-07-01

    Full Text Available Gene expression of the human immunodeficiency virus type 1 (HIV-1 is a highly regulated process. Basal transcription of the integrated provirus generates early transcripts that encode for the viral products Tat and Rev. Tat promotes the elongation of RNA polymerase while Rev mediates the nuclear export of viral RNAs that contain the Rev-responsive RNA element (RRE. These RNAs are exported from the nucleus to allow expression of Gag-Pol and Env proteins and for the production of full-length genomic RNAs. A balance exists between completely processed mRNAs and RRE-containing RNAs. Rev functions as an adaptor that recruits cellular factors to re-direct singly spliced and unspliced viral RNAs to nuclear export. The aim of this review is to address the dynamic regulation of this post-transcriptional pathway in light of recent findings that implicate several novel cellular cofactors of Rev function.

  18. VLSI circuits implementing computational models of neocortical circuits.

    Science.gov (United States)

    Wijekoon, Jayawan H B; Dudek, Piotr

    2012-09-15

    This paper overviews the design and implementation of three neuromorphic integrated circuits developed for the COLAMN ("Novel Computing Architecture for Cognitive Systems based on the Laminar Microcircuitry of the Neocortex") project. The circuits are implemented in a standard 0.35 μm CMOS technology and include spiking and bursting neuron models, and synapses with short-term (facilitating/depressing) and long-term (STDP and dopamine-modulated STDP) dynamics. They enable execution of complex nonlinear models in accelerated-time, as compared with biology, and with low power consumption. The neural dynamics are implemented using analogue circuit techniques, with digital asynchronous event-based input and output. The circuits provide configurable hardware blocks that can be used to simulate a variety of neural networks. The paper presents experimental results obtained from the fabricated devices, and discusses the advantages and disadvantages of the analogue circuit approach to computational neural modelling.

  19. Chemical memory reactions induced bursting dynamics in gene expression.

    Science.gov (United States)

    Tian, Tianhai

    2013-01-01

    Memory is a ubiquitous phenomenon in biological systems in which the present system state is not entirely determined by the current conditions but also depends on the time evolutionary path of the system. Specifically, many memorial phenomena are characterized by chemical memory reactions that may fire under particular system conditions. These conditional chemical reactions contradict to the extant stochastic approaches for modeling chemical kinetics and have increasingly posed significant challenges to mathematical modeling and computer simulation. To tackle the challenge, I proposed a novel theory consisting of the memory chemical master equations and memory stochastic simulation algorithm. A stochastic model for single-gene expression was proposed to illustrate the key function of memory reactions in inducing bursting dynamics of gene expression that has been observed in experiments recently. The importance of memory reactions has been further validated by the stochastic model of the p53-MDM2 core module. Simulations showed that memory reactions is a major mechanism for realizing both sustained oscillations of p53 protein numbers in single cells and damped oscillations over a population of cells. These successful applications of the memory modeling framework suggested that this innovative theory is an effective and powerful tool to study memory process and conditional chemical reactions in a wide range of complex biological systems.

  20. Dynamic development of the first synapse impinging on adult-born neurons in the olfactory bulb circuit.

    Science.gov (United States)

    Katagiri, Hiroyuki; Pallotto, Marta; Nissant, Antoine; Murray, Kerren; Sassoè-Pognetto, Marco; Lledo, Pierre-Marie

    2011-02-01

    The olfactory bulb (OB) receives and integrates newborn interneurons throughout life. This process is important for the proper functioning of the OB circuit and consequently, for the sense of smell. Although we know how these new interneurons are produced, the way in which they integrate into the pre-existing ongoing circuits remains poorly documented. Bearing in mind that glutamatergic inputs onto local OB interneurons are crucial for adjusting the level of bulbar inhibition, it is important to characterize when and how these inputs from excitatory synapses develop on newborn OB interneurons. We studied early synaptic events that lead to the formation and maturation of the first glutamatergic synapses on adult-born granule cells (GCs), the most abundant subtype of OB interneuron. Patch-clamp recordings and electron microscopy (EM) analysis were performed on adult-born interneurons shortly after their arrival in the adult OB circuits. We found that both the ratio of N-methyl-D-aspartate receptor (NMDAR) to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and the number of functional release sites at proximal inputs reached a maximum during the critical period for the sensory-dependent survival of newborn cells, well before the completion of dendritic arborization. EM analysis showed an accompanying change in postsynaptic density shape during the same period of time. Interestingly, the latter morphological changes disappeared in more mature newly-formed neurons, when the NMDAR to AMPAR ratio had decreased and functional presynaptic terminals expressed only single release sites. Together, these findings show that the first glutamatergic inputs to adult-generated OB interneurons undergo a unique sequence of maturation stages.

  1. Implementation on Electronic Circuits and RTR Pragmatical Adaptive Synchronization: Time-Reversed Uncertain Dynamical Systems' Analysis and Applications

    Directory of Open Access Journals (Sweden)

    Shih-Yu Li

    2013-01-01

    Full Text Available We expose the chaotic attractors of time-reversed nonlinear system, further implement its behavior on electronic circuit, and apply the pragmatical asymptotically stability theory to strictly prove that the adaptive synchronization of given master and slave systems with uncertain parameters can be achieved. In this paper, the variety chaotic motions of time-reversed Lorentz system are investigated through Lyapunov exponents, phase portraits, and bifurcation diagrams. For further applying the complex signal in secure communication and file encryption, we construct the circuit to show the similar chaotic signal of time-reversed Lorentz system. In addition, pragmatical asymptotically stability theorem and an assumption of equal probability for ergodic initial conditions (Ge et al., 1999, Ge and Yu, 2000, and Matsushima, 1972 are proposed to strictly prove that adaptive control can be accomplished successfully. The current scheme of adaptive control—by traditional Lyapunov stability theorem and Barbalat lemma, which are used to prove the error vector—approaches zero, as time approaches infinity. However, the core question—why the estimated or given parameters also approach to the uncertain parameters—remains without answer. By the new stability theory, those estimated parameters can be proved approaching the uncertain values strictly, and the simulation results are shown in this paper.

  2. Dynamic Modeling of Chain Circuit STATCOM%链式静止同步补偿器动态模型建模方法

    Institute of Scientific and Technical Information of China (English)

    王轩; 熊超英; 傅坚; 耿乾; 孙生鸿; 武守远; 林嘉扬

    2012-01-01

    摘要:链式结构静止同步补偿器(staticsynchronouscompensator,STATCOM)装置具有可分相控制、易于实现模块化设计、可靠性高、谐波特性好、无需多重化变压器、无需器件串联等显著优点,可改善系统暂态稳定,提高系统动态性能,改善用户电能质量,受到普遍重视。链式结构STATCOM的数学模型是研究相应控制策略及装置特性的基础。从单相H桥链节模型入手,研究单相链式STATCOM的动态模型建模方法,分别建立开关周期平均模型和小信号交流模型。通过仿真验证了所建模型的合理性,为装置级控制策略的研究奠定了理论基础。%Chain circuit static synchronous compensator (STATCOM) has significant advantages, such as easy to achieve split-control, simple to implement modular design, high reliability, good harmonic characteristics, no multi-transformer and no series connected power semiconductor devices, having been widely studied in improving system transient stability, system dynamic performance and customer power quality. Its mathematical model is the key to studying the corresponding control strategy and analyzing dynamic performance. This paper began with dynamics models of single-phase H-bridge, modeling of single-phase chain circuit STATCOM was studied, switching cycle average model and small signal AC model of single-phase chain circuit STATCOM were established. The simulation results verify the correctness and validity of the models, and the models can lay theoretical foundation for equipment-level control strategy study.

  3. A Two-Layered Diffusion Model Traces the Dynamics of Information Processing in the Valuation-and-Choice Circuit of Decision Making

    Directory of Open Access Journals (Sweden)

    Pietro Piu

    2014-01-01

    Full Text Available A circuit of evaluation and selection of the alternatives is considered a reliable model in neurobiology. The prominent contributions of the literature to this topic are reported. In this study, valuation and choice of a decisional process during Two-Alternative Forced-Choice (TAFC task are represented as a two-layered network of computational cells, where information accrual and processing progress in nonlinear diffusion dynamics. The evolution of the response-to-stimulus map is thus modeled by two linked diffusive modules (2LDM representing the neuronal populations involved in the valuation-and-decision circuit of decision making. Diffusion models are naturally appropriate for describing accumulation of evidence over the time. This allows the computation of the response times (RTs in valuation and choice, under the hypothesis of ex-Wald distribution. A nonlinear transfer function integrates the activities of the two layers. The input-output map based on the infomax principle makes the 2LDM consistent with the reinforcement learning approach. Results from simulated likelihood time series indicate that 2LDM may account for the activity-dependent modulatory component of effective connectivity between the neuronal populations. Rhythmic fluctuations of the estimate gain functions in the delta-beta bands also support the compatibility of 2LDM with the neurobiology of DM.

  4. Vibrational resonance and implementation of dynamic logic gate in a piecewise-linear Murali-Lakshmanan-Chua circuit

    Science.gov (United States)

    Venkatesh, P. R.; Venkatesan, A.

    2016-10-01

    We report the occurrence of vibrational resonance in piecewise-linear non-autonomous system. Especially, we show that an optimal amplitude of the high frequency second harmonic driving enhances the response of a piece-wise linear non-autonomous Murali-Lakshmanan-Chua (MLC) system to a low frequency first harmonic signal. This phenomenon is illustrated with the analytical solutions of circuit equations characterising the system and finally compared with the numerical method. Further, it has been enunciated explicitly, the implementation of the fundamental NOR/NAND gate via vibrational resonance, both by numerical and analytical solutions. In addition, these logical behaviours (AND/NAND/OR/NOR) can be decided by the amplitude of the input square waves without altering the system parameters.

  5. Effective Boolean dynamics analysis to identify functionally important genes in large-scale signaling networks.

    Science.gov (United States)

    Trinh, Hung-Cuong; Kwon, Yung-Keun

    2015-11-01

    Efficiently identifying functionally important genes in order to understand the minimal requirements of normal cellular development is challenging. To this end, a variety of structural measures have been proposed and their effectiveness has been investigated in recent literature; however, few studies have shown the effectiveness of dynamics-based measures. This led us to investigate a dynamic measure to identify functionally important genes, and the effectiveness of which was verified through application on two large-scale human signaling networks. We specifically consider Boolean sensitivity-based dynamics against an update-rule perturbation (BSU) as a dynamic measure. Through investigations on two large-scale human signaling networks, we found that genes with relatively high BSU values show slower evolutionary rate and higher proportions of essential genes and drug targets than other genes. Gene-ontology analysis showed clear differences between the former and latter groups of genes. Furthermore, we compare the identification accuracies of essential genes and drug targets via BSU and five well-known structural measures. Although BSU did not always show the best performance, it effectively identified the putative set of genes, which is significantly different from the results obtained via the structural measures. Most interestingly, BSU showed the highest synergy effect in identifying the functionally important genes in conjunction with other measures. Our results imply that Boolean-sensitive dynamics can be used as a measure to effectively identify functionally important genes in signaling networks.

  6. An ensemble method for identifying regulatory circuits with special reference to the qa gene cluster of Neurospora crassa

    Science.gov (United States)

    Battogtokh, D.; Asch, D. K.; Case, M. E.; Arnold, J.; Schüttler, H.-B.

    2002-01-01

    A chemical reaction network for the regulation of the quinic acid (qa) gene cluster of Neurospora crassa is proposed. An efficient Monte Carlo method for walking through the parameter space of possible chemical reaction networks is developed to identify an ensemble of deterministic kinetics models with rate constants consistent with RNA and protein profiling data. This method was successful in identifying a model ensemble fitting available RNA profiling data on the qa gene cluster. PMID:12477937

  7. Transcriptional Profiling of Newly Generated Dentate Granule Cells Using TU Tagging Reveals Pattern Shifts in Gene Expression during Circuit Integration1,2

    Science.gov (United States)

    Chatzi, Christina; Shen, Rongkun; Goodman, Richard H.

    2016-01-01

    Abstract Despite representing only a small fraction of hippocampal granule cells, adult-generated newborn granule cells have been implicated in learning and memory (Aimone et al., 2011). Newborn granule cells undergo functional maturation and circuit integration over a period of weeks. However, it is difficult to assess the accompanying gene expression profiles in vivo with high spatial and temporal resolution using traditional methods. Here we used a novel method [“thiouracil (TU) tagging”] to map the profiles of nascent mRNAs in mouse immature newborn granule cells compared with mature granule cells. We targeted a nonmammalian uracil salvage enzyme, uracil phosphoribosyltransferase, to newborn neurons and mature granule cells using retroviral and lentiviral constructs, respectively. Subsequent injection of 4-TU tagged nascent RNAs for analysis by RNA sequencing. Several hundred genes were significantly enhanced in the retroviral dataset compared with the lentiviral dataset. We compared a selection of the enriched genes with steady-state levels of mRNAs using quantitative PCR. Ontology analysis revealed distinct patterns of nascent mRNA expression, with newly generated immature neurons showing enhanced expression for genes involved in synaptic function, and neural differentiation and development, as well as genes not previously associated with granule cell maturation. Surprisingly, the nascent mRNAs enriched in mature cells were related to energy homeostasis and metabolism, presumably indicative of the increased energy demands of synaptic transmission and their complex dendritic architecture. The high spatial and temporal resolution of our modified TU-tagging method provides a foundation for comparison with steady-state RNA analyses by traditional transcriptomic approaches in defining the functional roles of newborn neurons. PMID:27011954

  8. Controllable circuit

    DEFF Research Database (Denmark)

    2010-01-01

    A switch-mode power circuit comprises a controllable element and a control unit. The controllable element is configured to control a current in response to a control signal supplied to the controllable element. The control unit is connected to the controllable element and provides the control...

  9. Design of Dual Dynamic Flip-Flop with Featuring Efficient Embedded Logic for Low Power Cmos Vlsi Circuits

    Directory of Open Access Journals (Sweden)

    Adhiyaman P1 ,

    2014-03-01

    Full Text Available In this paper, we introduce a new dual dynamic node hybrid flip-flop (DDFF and a novel embedded logic module (DDFF-ELM based on DDFF. The proposed designs eliminate the large capacitance present in the pre-charge node of several state-of-the-art designs by following a split dynamic node structure to separately drive the output pull-up and pull down transistors. The aim of the DDFF-ELM is to reduce pipeline overhead. It presents an area, power, and speed efficient method to incorporate complex logic functions into the flip-flop. The performance comparisons made in a 90 nm technology when compared to the Semi dynamic flip-flop, with no degradation in speed performance. The leakage power and process-voltage-temperature variations of various designs are studied in detail and are compared with the proposed designs.

  10. Low voltage logic circuits exploiting gate level dynamic body biasing in 28 nm UTBB FD-SOI

    Science.gov (United States)

    Taco, Ramiro; Levi, Itamar; Lanuzza, Marco; Fish, Alexander

    2016-03-01

    In this paper, the recently proposed gate level body bias (GLBB) technique is evaluated for low voltage logic design in state-of-the-art 28 nm ultra-thin body and box (UTBB) fully-depleted silicon-on-insulator (FD-SOI) technology. The inherent benefits of the low-granularity body-bias control, provided by the GLBB approach, are emphasized by the efficiency of forward body bias (FBB) in the FD-SOI technology. In addition, the possibility to integrate PMOS and NMOS devices into a single common well configuration allows significant area reduction, as compared to an equivalent triple well implementation. Some arithmetic circuits were designed using GLBB approach and compared to their conventional CMOS and DTMOS counterparts under different running conditions at low voltage regime. Simulation results shows that, for 300 mV of supply voltage, a 4 × 4-bit GLBB Baugh Wooley multiplier allows performance improvement of about 30% and area reduction of about 35%, while maintaining low energy consumption as compared to the conventional CMOS ⧹ DTMOS solutions. Performance and energy benefits are maintained over a wide range of process-voltage-temperature (PVT) variations.

  11. Dynamic changes in single unit activity and γ oscillations in a thalamocortical circuit during rapid instrumental learning.

    Science.gov (United States)

    Yu, Chunxiu; Fan, David; Lopez, Alberto; Yin, Henry H

    2012-01-01

    The medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) together form a thalamocortical circuit that has been implicated in the learning and production of goal-directed actions. In this study we measured neural activity in both regions simultaneously, as rats learned to press a lever to earn food rewards. In both MD and mPFC, instrumental learning was accompanied by dramatic changes in the firing patterns of the neurons, in particular the rapid emergence of single-unit neural activity reflecting the completion of the action and reward delivery. In addition, we observed distinct patterns of changes in the oscillatory LFP response in MD and mPFC. With learning, there was a significant increase in theta band oscillations (6-10 Hz) in the MD, but not in the mPFC. By contrast, gamma band oscillations (40-55 Hz) increased in the mPFC, but not in the MD. Coherence between these two regions also changed with learning: gamma coherence in relation to reward delivery increased, whereas theta coherence did not. Together these results suggest that, as rats learned the instrumental contingency between action and outcome, the emergence of task related neural activity is accompanied by enhanced functional interaction between MD and mPFC in response to the reward feedback.

  12. High-resolution mapping of bifurcations in nonlinear biochemical circuits

    Science.gov (United States)

    Genot, A. J.; Baccouche, A.; Sieskind, R.; Aubert-Kato, N.; Bredeche, N.; Bartolo, J. F.; Taly, V.; Fujii, T.; Rondelez, Y.

    2016-08-01

    Analog molecular circuits can exploit the nonlinear nature of biochemical reaction networks to compute low-precision outputs with fewer resources than digital circuits. This analog computation is similar to that employed by gene-regulation networks. Although digital systems have a tractable link between structure and function, the nonlinear and continuous nature of analog circuits yields an intricate functional landscape, which makes their design counter-intuitive, their characterization laborious and their analysis delicate. Here, using droplet-based microfluidics, we map with high resolution and dimensionality the bifurcation diagrams of two synthetic, out-of-equilibrium and nonlinear programs: a bistable DNA switch and a predator-prey DNA oscillator. The diagrams delineate where function is optimal, dynamics bifurcates and models fail. Inverse problem solving on these large-scale data sets indicates interference from enzymatic coupling. Additionally, data mining exposes the presence of rare, stochastically bursting oscillators near deterministic bifurcations.

  13. High-resolution mapping of bifurcations in nonlinear biochemical circuits.

    Science.gov (United States)

    Genot, A J; Baccouche, A; Sieskind, R; Aubert-Kato, N; Bredeche, N; Bartolo, J F; Taly, V; Fujii, T; Rondelez, Y

    2016-08-01

    Analog molecular circuits can exploit the nonlinear nature of biochemical reaction networks to compute low-precision outputs with fewer resources than digital circuits. This analog computation is similar to that employed by gene-regulation networks. Although digital systems have a tractable link between structure and function, the nonlinear and continuous nature of analog circuits yields an intricate functional landscape, which makes their design counter-intuitive, their characterization laborious and their analysis delicate. Here, using droplet-based microfluidics, we map with high resolution and dimensionality the bifurcation diagrams of two synthetic, out-of-equilibrium and nonlinear programs: a bistable DNA switch and a predator-prey DNA oscillator. The diagrams delineate where function is optimal, dynamics bifurcates and models fail. Inverse problem solving on these large-scale data sets indicates interference from enzymatic coupling. Additionally, data mining exposes the presence of rare, stochastically bursting oscillators near deterministic bifurcations.

  14. Functionality and Robustness of Injured Connectomic Dynamics in C. elegans: Linking Behavioral Deficits to Neural Circuit Damage

    Science.gov (United States)

    Kunert, James M.; Maia, Pedro D.; Kutz, J. Nathan

    2017-01-01

    Using a model for the dynamics of the full somatic nervous system of the nematode C. elegans, we address how biological network architectures and their functionality are degraded in the presence of focal axonal swellings (FAS) arising from neurodegenerative disease and/or traumatic brain injury. Using biophysically measured FAS distributions and swelling sizes, we are able to simulate the effects of injuries on the neural dynamics of C. elegans, showing how damaging the network degrades its low-dimensional dynamical responses. We visualize these injured neural dynamics by mapping them onto the worm’s low-dimensional postures, i.e. eigenworm modes. We show that a diversity of functional deficits arise from the same level of injury on a connectomic network. Functional deficits are quantified using a statistical shape analysis, a procrustes analysis, for deformations of the limit cycles that characterize key behaviors such as forward crawling. This procrustes metric carries information on the functional outcome of injuries in the model. Furthermore, we apply classification trees to relate injury structure to the behavioral outcome. This makes testable predictions for the structure of an injury given a defined functional deficit. More critically, this study demonstrates the potential role of computational simulation studies in understanding how neuronal networks process biological signals, and how this processing is impacted by network injury. PMID:28056097

  15. Non-equilibrium dynamics of gene expression and the Jarzynski equality

    OpenAIRE

    Berg, Johannes

    2007-01-01

    In order to express specific genes at the right time, the transcription of genes is regulated by the presence and absence of transcription factor molecules. With transcription factor concentrations undergoing constant changes, gene transcription takes place out of equilibrium. In this paper we discuss a simple mapping between dynamic models of gene expression and stochastic systems driven out of equilibrium. Using this mapping, results of nonequilibrium statistical mechanics such as the Jarzy...

  16. Fast-spiking GABA circuit dynamics in the auditory cortex predict recovery of sensory processing following peripheral nerve damage.

    Science.gov (United States)

    Resnik, Jennifer; Polley, Daniel B

    2017-03-21

    Cortical neurons remap their receptive fields and rescale sensitivity to spared peripheral inputs following sensory nerve damage. To address how these plasticity processes are coordinated over the course of functional recovery, we tracked receptive field reorganization, spontaneous activity, and response gain from individual principal neurons in the adult mouse auditory cortex over a 50-day period surrounding either moderate or massive auditory nerve damage. We related the day-by-day recovery of sound processing to dynamic changes in the strength of intracortical inhibition from parvalbumin-expressing (PV) inhibitory neurons. Whereas the status of brainstem-evoked potentials did not predict the recovery of sensory responses to surviving nerve fibers, homeostatic adjustments in PV-mediated inhibition during the first days following injury could predict the eventual recovery of cortical sound processing weeks later. These findings underscore the potential importance of self-regulated inhibitory dynamics for the restoration of sensory processing in excitatory neurons following peripheral nerve injuries.

  17. Developing a Domain Model for Relay Circuits

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth

    2009-01-01

    the statics as well as the dynamics of relay circuits, i.e. how a relay circuit can be composed legally from electrical components as well as how the components may change state over time. Finally the circuit model is transformed into an executable model, and we show how a concrete circuit can be defined......In this paper we stepwise develop a domain model for relay circuits as used in railway control systems. First we provide an abstract, property-oriented model of networks consisting of components that can be glued together with connectors. This model is strongly inspired by a network model...... for railways madeby Bjørner et.al., however our model is more general: the components can be of any kind and can later be refined to e.g. railway components or circuit components. Then we show how the abstract network model can be refined into an explicit model for relay circuits. The circuit model describes...

  18. Analog and VLSI circuits

    CERN Document Server

    Chen, Wai-Kai

    2009-01-01

    Featuring hundreds of illustrations and references, this book provides the information on analog and VLSI circuits. It focuses on analog integrated circuits, presenting the knowledge on monolithic device models, analog circuit cells, high performance analog circuits, RF communication circuits, and PLL circuits.

  19. Evolution dynamics of a model for gene duplication under adaptive conflict

    Science.gov (United States)

    Ancliff, Mark; Park, Jeong-Man

    2014-06-01

    We present and solve the dynamics of a model for gene duplication showing escape from adaptive conflict. We use a Crow-Kimura quasispecies model of evolution where the fitness landscape is a function of Hamming distances from two reference sequences, which are assumed to optimize two different gene functions, to describe the dynamics of a mixed population of individuals with single and double copies of a pleiotropic gene. The evolution equations are solved through a spin coherent state path integral, and we find two phases: one is an escape from an adaptive conflict phase, where each copy of a duplicated gene evolves toward subfunctionalization, and the other is a duplication loss of function phase, where one copy maintains its pleiotropic form and the other copy undergoes neutral mutation. The phase is determined by a competition between the fitness benefits of subfunctionalization and the greater mutational load associated with maintaining two gene copies. In the escape phase, we find a dynamics of an initial population of single gene sequences only which escape adaptive conflict through gene duplication and find that there are two time regimes: until a time t* single gene sequences dominate, and after t* double gene sequences outgrow single gene sequences. The time t* is identified as the time necessary for subfunctionalization to evolve and spread throughout the double gene sequences, and we show that there is an optimum mutation rate which minimizes this time scale.

  20. Dynamic evolution of bitter taste receptor genes in vertebrates

    Directory of Open Access Journals (Sweden)

    Jones Gareth

    2009-01-01

    Full Text Available Abstract Background Sensing bitter tastes is crucial for many animals because it can prevent them from ingesting harmful foods. This process is mainly mediated by the bitter taste receptors (T2R, which are largely expressed in the taste buds. Previous studies have identified some T2R gene repertoires, and marked variation in repertoire size has been noted among species. However, the mechanisms underlying the evolution of vertebrate T2R genes remain poorly understood. Results To better understand the evolutionary pattern of these genes, we identified 16 T2R gene repertoires based on the high coverage genome sequences of vertebrates and studied the evolutionary changes in the number of T2R genes during birth-and-death evolution using the reconciled-tree method. We found that the number of T2R genes and the fraction of pseudogenes vary extensively among species. Based on the results of phylogenetic analysis, we showed that T2R gene families in teleost fishes are more diverse than those in tetrapods. In addition to the independent gene expansions in teleost fishes, frogs and mammals, lineage-specific gene duplications were also detected in lizards. Furthermore, extensive gains and losses of T2R genes were detected in each lineage during their evolution, resulting in widely differing T2R gene repertoires. Conclusion These results further support the hypotheses that T2R gene repertoires are closely related to the dietary habits of different species and that birth-and-death evolution is associated with adaptations to dietary changes.

  1. Circuit Connectors

    Science.gov (United States)

    1979-01-01

    The U-shaped wire devices in the upper photo are Digi-Klipsm; aids to compact packaging of electrical and electronic devices. They serve as connectors linking the circuitry of one circuit board with another in multi-board systems. Digi-Klips were originally developed for Goddard Space Flight Center to meet a need for lightweight, reliable connectors to replace hand-wired connections formerly used in spacecraft. They are made of beryllium copper wire, noted for its excellent conductivity and its spring-like properties, which assure solid electrical contact over a long period of time.

  2. Programmable genetic circuits for pathway engineering.

    Science.gov (United States)

    Hoynes-O'Connor, Allison; Moon, Tae Seok

    2015-12-01

    Synthetic biology has the potential to provide decisive advances in genetic control of metabolic pathways. However, there are several challenges that synthetic biologists must overcome before this vision becomes a reality. First, a library of diverse and well-characterized sensors, such as metabolite-sensing or condition-sensing promoters, must be constructed. Second, robust programmable circuits that link input conditions with a specific gene regulation response must be developed. Finally, multi-gene targeting strategies must be integrated with metabolically relevant sensors and complex, robust logic. Achievements in each of these areas, which employ the CRISPR/Cas system, in silico modeling, and dynamic sensor-regulators, among other tools, provide a strong basis for future research. Overall, the future for synthetic biology approaches in metabolic engineering holds immense promise.

  3. Evolutionary Fates and Dynamic Functionalization of Young Duplicate Genes in Arabidopsis Genomes1[OPEN

    Science.gov (United States)

    Wang, Jun; Tao, Feng; Marowsky, Nicholas C.; Fan, Chuanzhu

    2016-01-01

    Gene duplication is a primary means to generate genomic novelties, playing an essential role in speciation and adaptation. Particularly in plants, a high abundance of duplicate genes has been maintained for significantly long periods of evolutionary time. To address the manner in which young duplicate genes were derived primarily from small-scale gene duplication and preserved in plant genomes and to determine the underlying driving mechanisms, we generated transcriptomes to produce the expression profiles of five tissues in Arabidopsis thaliana and the closely related species Arabidopsis lyrata and Capsella rubella. Based on the quantitative analysis metrics, we investigated the evolutionary processes of young duplicate genes in Arabidopsis. We determined that conservation, neofunctionalization, and specialization are three main evolutionary processes for Arabidopsis young duplicate genes. We explicitly demonstrated the dynamic functionalization of duplicate genes along the evolutionary time scale. Upon origination, duplicates tend to maintain their ancestral functions; but as they survive longer, they might be likely to develop distinct and novel functions. The temporal evolutionary processes and functionalization of plant duplicate genes are associated with their ancestral functions, dynamic DNA methylation levels, and histone modification abundances. Furthermore, duplicate genes tend to be initially expressed in pollen and then to gain more interaction partners over time. Altogether, our study provides novel insights into the dynamic retention processes of young duplicate genes in plant genomes. PMID:27485883

  4. Reverse engineering gene networks: Integrating genetic perturbations with dynamical modeling

    Science.gov (United States)

    Tegnér, Jesper; Yeung, M. K. Stephen; Hasty, Jeff; Collins, James J.

    2003-01-01

    While the fundamental building blocks of biology are being tabulated by the various genome projects, microarray technology is setting the stage for the task of deducing the connectivity of large-scale gene networks. We show how the perturbation of carefully chosen genes in a microarray experiment can be used in conjunction with a reverse engineering algorithm to reveal the architecture of an underlying gene regulatory network. Our iterative scheme identifies the network topology by analyzing the steady-state changes in gene expression resulting from the systematic perturbation of a particular node in the network. We highlight the validity of our reverse engineering approach through the successful deduction of the topology of a linear in numero gene network and a recently reported model for the segmentation polarity network in Drosophila melanogaster. Our method may prove useful in identifying and validating specific drug targets and in deconvolving the effects of chemical compounds. PMID:12730377

  5. Dynamic and reversibility of heterochromatic gene silencing in human disease

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    In eukaryotic organisms cellular fate and tissue specific gene expression are regulated by the activity of proteins known as transcription factors that by interacting with specific DNA sequences direct the activation or repression of target genes. The post genomic era has shown that transcription factors are not the unique key regulators of gene expression. Epigenetic mechanisms such as DNA methylation, post-translational modifications of histone proteins,remodeling of nucleosomes and expression of small regulatory RNAs also contribute to regulation of gene expression,determination of cell and tissue specificity and assurance of inheritance of gene expression levels. The relevant contribution of epigenetic mechanisms to a proper cellular function is highlighted by the effects of their deregulation that cooperate with genetic alterations to the development of various diseases and to the establishment and progression of tumors.

  6. LOGIC CIRCUIT

    Science.gov (United States)

    Strong, G.H.; Faught, M.L.

    1963-12-24

    A device for safety rod counting in a nuclear reactor is described. A Wheatstone bridge circuit is adapted to prevent de-energizing the hopper coils of a ball backup system if safety rods, sufficient in total control effect, properly enter the reactor core to effect shut down. A plurality of resistances form one arm of the bridge, each resistance being associated with a particular safety rod and weighted in value according to the control effect of the particular safety rod. Switching means are used to switch each of the resistances in and out of the bridge circuit responsive to the presence of a particular safety rod in its effective position in the reactor core and responsive to the attainment of a predetermined velocity by a particular safety rod enroute to its effective position. The bridge is unbalanced in one direction during normal reactor operation prior to the generation of a scram signal and the switching means and resistances are adapted to unbalance the bridge in the opposite direction if the safety rods produce a predetermined amount of control effect in response to the scram signal. The bridge unbalance reversal is then utilized to prevent the actuation of the ball backup system, or, conversely, a failure of the safety rods to produce the predetermined effect produces no unbalance reversal and the ball backup system is actuated. (AEC)

  7. A model of gene expression based on random dynamical systems reveals modularity properties of gene regulatory networks.

    Science.gov (United States)

    Antoneli, Fernando; Ferreira, Renata C; Briones, Marcelo R S

    2016-06-01

    Here we propose a new approach to modeling gene expression based on the theory of random dynamical systems (RDS) that provides a general coupling prescription between the nodes of any given regulatory network given the dynamics of each node is modeled by a RDS. The main virtues of this approach are the following: (i) it provides a natural way to obtain arbitrarily large networks by coupling together simple basic pieces, thus revealing the modularity of regulatory networks; (ii) the assumptions about the stochastic processes used in the modeling are fairly general, in the sense that the only requirement is stationarity; (iii) there is a well developed mathematical theory, which is a blend of smooth dynamical systems theory, ergodic theory and stochastic analysis that allows one to extract relevant dynamical and statistical information without solving the system; (iv) one may obtain the classical rate equations form the corresponding stochastic version by averaging the dynamic random variables (small noise limit). It is important to emphasize that unlike the deterministic case, where coupling two equations is a trivial matter, coupling two RDS is non-trivial, specially in our case, where the coupling is performed between a state variable of one gene and the switching stochastic process of another gene and, hence, it is not a priori true that the resulting coupled system will satisfy the definition of a random dynamical system. We shall provide the necessary arguments that ensure that our coupling prescription does indeed furnish a coupled regulatory network of random dynamical systems. Finally, the fact that classical rate equations are the small noise limit of our stochastic model ensures that any validation or prediction made on the basis of the classical theory is also a validation or prediction of our model. We illustrate our framework with some simple examples of single-gene system and network motifs.

  8. Is transcription the dominant force during dynamic changes in gene expression?

    Science.gov (United States)

    Turner, Martin

    2011-01-01

    Dynamic changes in gene expression punctuate lymphocyte development and are a characteristic of lymphocyte activation. A prevailing view has been that these changes are driven by DNA transcription factors, which are the dominant force in gene expression. Accumulating evidence is challenging this DNA centric view and has highlighted the prevalence and dynamic nature of RNA handling mechanisms. Alternative splicing and differential polyadenylation appear to be more widespread than first thought. Changes in mRNA decay rates also affect the abundance of transcripts and this mechanism may contribute significantly to gene expression. Additional RNA handling mechanisms that control the intracellular localization of mRNA and association with translating ribosomes are also important. Thus, gene expression is regulated through the coordination of transcriptional and post-transcriptional mechanisms. Developing a more "RNA centric" view of gene expression will allow a more systematic understanding of how gene expression and cell function are integrated.

  9. Collective of mechatronics circuit

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1987-02-15

    This book is composed of three parts, which deals with mechatronics system about sensor, circuit and motor. The contents of the first part are photo sensor of collector for output, locating detection circuit with photo interrupts, photo sensor circuit with CdS cell and lamp, interface circuit with logic and LED and temperature sensor circuit. The second part deals with oscillation circuit with crystal, C-R oscillation circuit, F-V converter, timer circuit, stability power circuit, DC amp and DC-DC converter. The last part is comprised of bridge server circuit, deformation bridge server, controlling circuit of DC motor, controlling circuit with IC for PLL and driver circuit of stepping motor and driver circuit of Brushless.

  10. Visualization of the Dynamics of Gene Expression in the Living Mouse

    Directory of Open Access Journals (Sweden)

    Amy Ryan

    2004-01-01

    Full Text Available Reporter genes can monitor the status and activity of recombinant genomes in a diverse array of organisms, from bacteria and yeast to plants and animals. We have combined luciferase reporter genes with a conditional gene expression system based on regulatory elements from the lac Operon of Escherichia coli to visualize the dynamics of gene expression in realtime in the living mouse. Using this technology, we have determined the rate of gene induction and repression, the level of target gene activity in response to different doses of inducer, and the schedule of induction during early embryogenesis of both the endogenous and the experimentally manipulated programs of mammalian gene expression associated with the HD/Hdh locus. The combination of in vivo imaging and lac regulation is a powerful tool for generating conditional transgenic mice that can be screened rapidly for optimal regulation and expression patterns, and for monitoring the induction and repression of regulated genes noninvasively in the living animal.

  11. Variational integrators for electric circuits

    Energy Technology Data Exchange (ETDEWEB)

    Ober-Blöbaum, Sina, E-mail: sinaob@math.upb.de [Computational Dynamics and Optimal Control, University of Paderborn (Germany); Tao, Molei [Courant Institute of Mathematical Sciences, New York University (United States); Cheng, Mulin [Applied and Computational Mathematics, California Institute of Technology (United States); Owhadi, Houman; Marsden, Jerrold E. [Control and Dynamical Systems, California Institute of Technology (United States); Applied and Computational Mathematics, California Institute of Technology (United States)

    2013-06-01

    In this contribution, we develop a variational integrator for the simulation of (stochastic and multiscale) electric circuits. When considering the dynamics of an electric circuit, one is faced with three special situations: 1. The system involves external (control) forcing through external (controlled) voltage sources and resistors. 2. The system is constrained via the Kirchhoff current (KCL) and voltage laws (KVL). 3. The Lagrangian is degenerate. Based on a geometric setting, an appropriate variational formulation is presented to model the circuit from which the equations of motion are derived. A time-discrete variational formulation provides an iteration scheme for the simulation of the electric circuit. Dependent on the discretization, the intrinsic degeneracy of the system can be canceled for the discrete variational scheme. In this way, a variational integrator is constructed that gains several advantages compared to standard integration tools for circuits; in particular, a comparison to BDF methods (which are usually the method of choice for the simulation of electric circuits) shows that even for simple LCR circuits, a better energy behavior and frequency spectrum preservation can be observed using the developed variational integrator.

  12. Gene x environment interactions as dynamical systems: clinical implications

    National Research Council Canada - National Science Library

    Sarah S. Knox

    2015-01-01

    The etiology and progression of the chronic diseases that account for the highest rates of mortality in the US, namely, cardiovascular diseases and cancers, involve complex gene x environment interactions...

  13. Dynamic evolution of bitter taste receptor genes in vertebrates

    OpenAIRE

    Jones Gareth; Dong Dong; Zhang Shuyi

    2009-01-01

    Abstract Background Sensing bitter tastes is crucial for many animals because it can prevent them from ingesting harmful foods. This process is mainly mediated by the bitter taste receptors (T2R), which are largely expressed in the taste buds. Previous studies have identified some T2R gene repertoires, and marked variation in repertoire size has been noted among species. However, the mechanisms underlying the evolution of vertebrate T2R genes remain poorly understood. Results To better unders...

  14. Chaos Control for Chua's Circuits

    Science.gov (United States)

    Tôrres, L. A. B.; Aguirre, L. A.; Palhares, R. M.; Mendes, E. M. A. M.

    The practical implementation of Chua's circuit control methods is discussed in this chapter. In order to better address this subject, an inductorless Chua's circuit realization is first presented, followed by practical issues related to data analysis, mathematical modelling, and dynamical characterization associated to this electronic chaotic oscillator. As a consequence of the investigation of different control strategies applied to Chua's circuit, a tradeoff among control objective, control energy, and model complexity is devised, which quite naturally leads to a principle that seems to be of general nature: the Information Transmission Via Control (ITVC) for nonlinear oscillators. The main purpose of the present chapter is to serve as an introductory guide to the universe of Chua's circuit control, synchronization, and mathematical modelling.

  15. High Dimensional ODEs Coupled with Mixed-Effects Modeling Techniques for Dynamic Gene Regulatory Network Identification.

    Science.gov (United States)

    Lu, Tao; Liang, Hua; Li, Hongzhe; Wu, Hulin

    2011-01-01

    Gene regulation is a complicated process. The interaction of many genes and their products forms an intricate biological network. Identification of this dynamic network will help us understand the biological process in a systematic way. However, the construction of such a dynamic network is very challenging for a high-dimensional system. In this article we propose to use a set of ordinary differential equations (ODE), coupled with dimensional reduction by clustering and mixed-effects modeling techniques, to model the dynamic gene regulatory network (GRN). The ODE models allow us to quantify both positive and negative gene regulations as well as feedback effects of one set of genes in a functional module on the dynamic expression changes of the genes in another functional module, which results in a directed graph network. A five-step procedure, Clustering, Smoothing, regulation Identification, parameter Estimates refining and Function enrichment analysis (CSIEF) is developed to identify the ODE-based dynamic GRN. In the proposed CSIEF procedure, a series of cutting-edge statistical methods and techniques are employed, that include non-parametric mixed-effects models with a mixture distribution for clustering, nonparametric mixed-effects smoothing-based methods for ODE models, the smoothly clipped absolute deviation (SCAD)-based variable selection, and stochastic approximation EM (SAEM) approach for mixed-effects ODE model parameter estimation. The key step, the SCAD-based variable selection of the proposed procedure is justified by investigating its asymptotic properties and validated by Monte Carlo simulations. We apply the proposed method to identify the dynamic GRN for yeast cell cycle progression data. We are able to annotate the identified modules through function enrichment analyses. Some interesting biological findings are discussed. The proposed procedure is a promising tool for constructing a general dynamic GRN and more complicated dynamic networks.

  16. Commutation circuit for an HVDC circuit breaker

    Science.gov (United States)

    Premerlani, William J.

    1981-01-01

    A commutation circuit for a high voltage DC circuit breaker incorporates a resistor capacitor combination and a charging circuit connected to the main breaker, such that a commutating capacitor is discharged in opposition to the load current to force the current in an arc after breaker opening to zero to facilitate arc interruption. In a particular embodiment, a normally open commutating circuit is connected across the contacts of a main DC circuit breaker to absorb the inductive system energy trapped by breaker opening and to limit recovery voltages to a level tolerable by the commutating circuit components.

  17. Runx Family Genes in Tissue Stem Cell Dynamics.

    Science.gov (United States)

    Wang, Chelsia Qiuxia; Mok, Michelle Meng Huang; Yokomizo, Tomomasa; Tergaonkar, Vinay; Osato, Motomi

    2017-01-01

    The Runx family genes play important roles in development and cancer, largely via their regulation of tissue stem cell behavior. Their involvement in two organs, blood and skin, is well documented. This review summarizes currently known Runx functions in the stem cells of these tissues. The fundamental core mechanism(s) mediated by Runx proteins has been sought; however, it appears that there does not exist one single common machinery that governs both tissue stem cells. Instead, Runx family genes employ multiple spatiotemporal mechanisms in regulating individual tissue stem cell populations. Such specific Runx requirements have been unveiled by a series of cell type-, developmental stage- or age-specific gene targeting studies in mice. Observations from these experiments revealed that the regulation of stem cells by Runx family genes turned out to be far more complex than previously thought. For instance, although it has been reported that Runx1 is required for the endothelial-to-hematopoietic cell transition (EHT) but not thereafter, recent studies clearly demonstrated that Runx1 is also needed during the period subsequent to EHT, namely at perinatal stage. In addition, Runx1 ablation in the embryonic skin mesenchyme eventually leads to complete loss of hair follicle stem cells (HFSCs) in the adult epithelium, suggesting that Runx1 facilitates the specification of skin epithelial stem cells in a cell extrinsic manner. Further in-depth investigation into how Runx family genes are involved in stem cell regulation is warranted.

  18. Nonsmooth Modeling and Simulation for Switched Circuits

    CERN Document Server

    Acary, Vincent; Brogliato, Bernard

    2011-01-01

    "Nonsmooth Modeling and Simulation for Switched Circuits" concerns the modeling and the numerical simulation of switched circuits with the nonsmooth dynamical systems (NSDS) approach, using piecewise-linear and multivalued models of electronic devices like diodes, transistors, switches. Numerous examples (ranging from introductory academic circuits to various types of power converters) are analyzed and many simulation results obtained with the INRIA open-source SICONOS software package are presented. Comparisons with SPICE and hybrid methods demonstrate the power of the NSDS approach

  19. Microbiota diversity and gene expression dynamics in human oral biofilms.

    Science.gov (United States)

    Benítez-Páez, Alfonso; Belda-Ferre, Pedro; Simón-Soro, Aurea; Mira, Alex

    2014-04-27

    Micro-organisms inhabiting teeth surfaces grow on biofilms where a specific and complex succession of bacteria has been described by co-aggregation tests and DNA-based studies. Although the composition of oral biofilms is well established, the active portion of the bacterial community and the patterns of gene expression in vivo have not been studied. Using RNA-sequencing technologies, we present the first metatranscriptomic study of human dental plaque, performed by two different approaches: (1) A short-reads, high-coverage approach by Illumina sequencing to characterize the gene activity repertoire of the microbial community during biofilm development; (2) A long-reads, lower-coverage approach by pyrosequencing to determine the taxonomic identity of the active microbiome before and after a meal ingestion. The high-coverage approach allowed us to analyze over 398 million reads, revealing that microbial communities are individual-specific and no bacterial species was detected as key player at any time during biofilm formation. We could identify some gene expression patterns characteristic for early and mature oral biofilms. The transcriptomic profile of several adhesion genes was confirmed through qPCR by measuring expression of fimbriae-associated genes. In addition to the specific set of gene functions overexpressed in early and mature oral biofilms, as detected through the short-reads dataset, the long-reads approach detected specific changes when comparing the metatranscriptome of the same individual before and after a meal, which can narrow down the list of organisms responsible for acid production and therefore potentially involved in dental caries. The bacteria changing activity during biofilm formation and after meal ingestion were person-specific. Interestingly, some individuals showed extreme homeostasis with virtually no changes in the active bacterial population after food ingestion, suggesting the presence of a microbial community which could be

  20. Phylogenomic analysis reveals dynamic evolutionary history of the Drosophila heterochromatin protein 1 (HP1 gene family.

    Directory of Open Access Journals (Sweden)

    Mia T Levine

    Full Text Available Heterochromatin is the gene-poor, satellite-rich eukaryotic genome compartment that supports many essential cellular processes. The functional diversity of proteins that bind and often epigenetically define heterochromatic DNA sequence reflects the diverse functions supported by this enigmatic genome compartment. Moreover, heterogeneous signatures of selection at chromosomal proteins often mirror the heterogeneity of evolutionary forces that act on heterochromatic DNA. To identify new such surrogates for dissecting heterochromatin function and evolution, we conducted a comprehensive phylogenomic analysis of the Heterochromatin Protein 1 gene family across 40 million years of Drosophila evolution. Our study expands this gene family from 5 genes to at least 26 genes, including several uncharacterized genes in Drosophila melanogaster. The 21 newly defined HP1s introduce unprecedented structural diversity, lineage-restriction, and germline-biased expression patterns into the HP1 family. We find little evidence of positive selection at these HP1 genes in both population genetic and molecular evolution analyses. Instead, we find that dynamic evolution occurs via prolific gene gains and losses. Despite this dynamic gene turnover, the number of HP1 genes is relatively constant across species. We propose that karyotype evolution drives at least some HP1 gene turnover. For example, the loss of the male germline-restricted HP1E in the obscura group coincides with one episode of dramatic karyotypic evolution, including the gain of a neo-Y in this lineage. This expanded compendium of ovary- and testis-restricted HP1 genes revealed by our study, together with correlated gain/loss dynamics and chromosome fission/fusion events, will guide functional analyses of novel roles supported by germline chromatin.

  1. Calcisponges have a ParaHox gene and dynamic expression of dispersed NK homeobox genes.

    Science.gov (United States)

    Fortunato, Sofia A V; Adamski, Marcin; Ramos, Olivia Mendivil; Leininger, Sven; Liu, Jing; Ferrier, David E K; Adamska, Maja

    2014-10-30

    Sponges are simple animals with few cell types, but their genomes paradoxically contain a wide variety of developmental transcription factors, including homeobox genes belonging to the Antennapedia (ANTP) class, which in bilaterians encompass Hox, ParaHox and NK genes. In the genome of the demosponge Amphimedon queenslandica, no Hox or ParaHox genes are present, but NK genes are linked in a tight cluster similar to the NK clusters of bilaterians. It has been proposed that Hox and ParaHox genes originated from NK cluster genes after divergence of sponges from the lineage leading to cnidarians and bilaterians. On the other hand, synteny analysis lends support to the notion that the absence of Hox and ParaHox genes in Amphimedon is a result of secondary loss (the ghost locus hypothesis). Here we analysed complete suites of ANTP-class homeoboxes in two calcareous sponges, Sycon ciliatum and Leucosolenia complicata. Our phylogenetic analyses demonstrate that these calcisponges possess orthologues of bilaterian NK genes (Hex, Hmx and Msx), a varying number of additional NK genes and one ParaHox gene, Cdx. Despite the generation of scaffolds spanning multiple genes, we find no evidence of clustering of Sycon NK genes. All Sycon ANTP-class genes are developmentally expressed, with patterns suggesting their involvement in cell type specification in embryos and adults, metamorphosis and body plan patterning. These results demonstrate that ParaHox genes predate the origin of sponges, thus confirming the ghost locus hypothesis, and highlight the need to analyse the genomes of multiple sponge lineages to obtain a complete picture of the ancestral composition of the first animal genome.

  2. Developmental dynamics of floral gene regulation [ChIP-Seq

    NARCIS (Netherlands)

    Pajoro, A.; Madrigal, P.; Kaufmann, K.

    2014-01-01

    Development of eukaryotic organisms is controlled by transcription factors that trigger specific and global changes in gene expression programmes. In plants, MADS-domain transcription factors act as master regulators of developmental switches and organ specification. However, the mechanisms by which

  3. Dynamic monitoring of horizontal gene transfer in soil

    Science.gov (United States)

    Cheng, H. Y.; Masiello, C. A.; Silberg, J. J.; Bennett, G. N.

    2015-12-01

    Soil microbial gene expression underlies microbial behaviors (phenotypes) central to many aspects of C, N, and H2O cycling. However, continuous monitoring of microbial gene expression in soils is challenging because genetically-encoded reporter proteins widely used in the lab are difficult to deploy in soil matrices: for example, green fluorescent protein cannot be easily visualized in soils, even in the lab. To address this problem we have developed a reporter protein that releases small volatile gases. Here, we applied this gas reporter in a proof-of-concept soil experiment, monitoring horizontal gene transfer, a microbial activity that alters microbial genotypes and phenotypes. Horizontal gene transfer is central to bacterial evolution and adaptation and is relevant to problems such as the spread of antibiotic resistance, increasing metal tolerance in superfund sites, and bioremediation capability of bacterial consortia. This process is likely to be impacted by a number of matrix properties not well-represented in the petri dish, such as microscale variations in water, nutrients, and O2, making petri-dish experiments a poor proxy for environmental processes. We built a conjugation system using synthetic biology to demonstrate the use of gas-reporting biosensors in safe, lab-based biogeochemistry experiments, and here we report the use of these sensors to monitor horizontal gene transfer in soils. Our system is based on the F-plasmid conjugation in Escherichia coli. We have found that the gas signal reports on the number of cells that acquire F-plasmids (transconjugants) in a loamy Alfisol collected from Kellogg Biological Station. We will report how a gas signal generated by transconjugants varies with the number of F-plasmid donor and acceptor cells seeded in a soil, soil moisture, and soil O2 levels.

  4. Targeting c-Myc-activated genes with a correlation method: Detection of global changes in large gene expression network dynamics

    Science.gov (United States)

    Remondini, D.; O'Connell, B.; Intrator, N.; Sedivy, J. M.; Neretti, N.; Castellani, G. C.; Cooper, L. N.

    2005-01-01

    This work studies the dynamics of a gene expression time series network. The network, which is obtained from the correlation of gene expressions, exhibits global dynamic properties that emerge after a cell state perturbation. The main features of this network appear to be more robust when compared with those obtained with a network obtained from a linear Markov model. In particular, the network properties strongly depend on the exact time sequence relationships between genes and are destroyed by random temporal data shuffling. We discuss in detail the problem of finding targets of the c-myc protooncogene, which encodes a transcriptional regulator whose inappropriate expression has been correlated with a wide array of malignancies. The data used for network construction are a time series of gene expression, collected by microarray analysis of a rat fibroblast cell line expressing a conditional Myc-estrogen receptor oncoprotein. We show that the correlation-based model can establish a clear relationship between network structure and the cascade of c-myc-activated genes. PMID:15867157

  5. Evolutionary dynamics of human autoimmune disease genes and malfunctioned immunological genes

    Directory of Open Access Journals (Sweden)

    Podder Soumita

    2012-01-01

    Full Text Available Abstract Background One of the main issues of molecular evolution is to divulge the principles in dictating the evolutionary rate differences among various gene classes. Immunological genes have received considerable attention in evolutionary biology as candidates for local adaptation and for studying functionally important polymorphisms. The normal structure and function of immunological genes will be distorted when they experience mutations leading to immunological dysfunctions. Results Here, we examined the fundamental differences between the genes which on mutation give rise to autoimmune or other immune system related diseases and the immunological genes that do not cause any disease phenotypes. Although the disease genes examined are analogous to non-disease genes in product, expression, function, and pathway affiliation, a statistically significant decrease in evolutionary rate has been found in autoimmune disease genes relative to all other immune related diseases and non-disease genes. Possible ways of accumulation of mutation in the three steps of the central dogma (DNA-mRNA-Protein have been studied to trace the mutational effects predisposed to disease consequence and acquiring higher selection pressure. Principal Component Analysis and Multivariate Regression Analysis have established the predominant role of single nucleotide polymorphisms in guiding the evolutionary rate of immunological disease and non-disease genes followed by m-RNA abundance, paralogs number, fraction of phosphorylation residue, alternatively spliced exon, protein residue burial and protein disorder. Conclusions Our study provides an empirical insight into the etiology of autoimmune disease genes and other immunological diseases. The immediate utility of our study is to help in disease gene identification and may also help in medicinal improvement of immune related disease.

  6. Current Control Strategy of Chain Circuit STATCOM

    Institute of Scientific and Technical Information of China (English)

    WANG Xuan; FU Jian; TENG Letian; SUN Lijing; ZHAO Ruibin; WU Shouyuan; DENG Zhanfeng

    2012-01-01

    In order to study the current control strategy based on the chain circuit static synchronous compensator (STATCOM) dynamic model and the design control system with good stability and tracking accuracy, this paper applies the chain circuit STATCOM small signal AC model, and proposes the following assumptions:

  7. Analog circuit design designing waveform processing circuits

    CERN Document Server

    Feucht, Dennis

    2010-01-01

    The fourth volume in the set Designing Waveform-Processing Circuits builds on the previous 3 volumes and presents a variety of analog non-amplifier circuits, including voltage references, current sources, filters, hysteresis switches and oscilloscope trigger and sweep circuitry, function generation, absolute-value circuits, and peak detectors.

  8. Evolutionary history of chordate PAX genes: dynamics of change in a complex gene family.

    Directory of Open Access Journals (Sweden)

    Vanessa Rodrigues Paixão-Côrtes

    Full Text Available Paired box (PAX genes are transcription factors that play important roles in embryonic development. Although the PAX gene family occurs in animals only, it is widely distributed. Among the vertebrates, its 9 genes appear to be the product of complete duplication of an original set of 4 genes, followed by an additional partial duplication. Although some studies of PAX genes have been conducted, no comprehensive survey of these genes across the entire taxonomic unit has yet been attempted. In this study, we conducted a detailed comparison of PAX sequences from 188 chordates, which revealed restricted variation. The absence of PAX4 and PAX8 among some species of reptiles and birds was notable; however, all 9 genes were present in all 74 mammalian genomes investigated. A search for signatures of selection indicated that all genes are subject to purifying selection, with a possible constraint relaxation in PAX4, PAX7, and PAX8. This result indicates asymmetric evolution of PAX family genes, which can be associated with the emergence of adaptive novelties in the chordate evolutionary trajectory.

  9. Synthetic Biology: A Unifying View and Review Using Analog Circuits.

    Science.gov (United States)

    Teo, Jonathan J Y; Woo, Sung Sik; Sarpeshkar, Rahul

    2015-08-01

    We review the field of synthetic biology from an analog circuits and analog computation perspective, focusing on circuits that have been built in living cells. This perspective is well suited to pictorially, symbolically, and quantitatively representing the nonlinear, dynamic, and stochastic (noisy) ordinary and partial differential equations that rigorously describe the molecular circuits of synthetic biology. This perspective enables us to construct a canonical analog circuit schematic that helps unify and review the operation of many fundamental circuits that have been built in synthetic biology at the DNA, RNA, protein, and small-molecule levels over nearly two decades. We review 17 circuits in the literature as particular examples of feedforward and feedback analog circuits that arise from special topological cases of the canonical analog circuit schematic. Digital circuit operation of these circuits represents a special case of saturated analog circuit behavior and is automatically incorporated as well. Many issues that have prevented synthetic biology from scaling are naturally represented in analog circuit schematics. Furthermore, the deep similarity between the Boltzmann thermodynamic equations that describe noisy electronic current flow in subthreshold transistors and noisy molecular flux in biochemical reactions has helped map analog circuit motifs in electronics to analog circuit motifs in cells and vice versa via a `cytomorphic' approach. Thus, a body of knowledge in analog electronic circuit design, analysis, simulation, and implementation may also be useful in the robust and efficient design of molecular circuits in synthetic biology, helping it to scale to more complex circuits in the future.

  10. Tracing the dynamics of gene transcripts after organismal death

    Science.gov (United States)

    2017-01-01

    In life, genetic and epigenetic networks precisely coordinate the expression of genes—but in death, it is not known if gene expression diminishes gradually or abruptly stops or if specific genes and pathways are involved. We studied this by identifying mRNA transcripts that apparently increase in relative abundance after death, assessing their functions, and comparing their abundance profiles through postmortem time in two species, mouse and zebrafish. We found mRNA transcript profiles of 1063 genes became significantly more abundant after death of healthy adult animals in a time series spanning up to 96 h postmortem. Ordination plots revealed non-random patterns in the profiles by time. While most of these transcript levels increased within 0.5 h postmortem, some increased only at 24 and 48 h postmortem. Functional characterization of the most abundant transcripts revealed the following categories: stress, immunity, inflammation, apoptosis, transport, development, epigenetic regulation and cancer. The data suggest a step-wise shutdown occurs in organismal death that is manifested by the apparent increase of certain transcripts with various abundance maxima and durations. PMID:28123054

  11. Abundance and dynamics of antibiotic resistance genes and integrons in lake sediment microcosms.

    Directory of Open Access Journals (Sweden)

    Björn Berglund

    Full Text Available Antibiotic resistance in bacteria causing disease is an ever growing threat to the world. Recently, environmental bacteria have become established as important both as sources of antibiotic resistance genes and in disseminating resistance genes. Low levels of antibiotics and other pharmaceuticals are regularly released into water environments via wastewater, and the concern is that such environmental contamination may serve to create hotspots for antibiotic resistance gene selection and dissemination. In this study, microcosms were created from water and sediments gathered from a lake in Sweden only lightly affected by human activities. The microcosms were exposed to a mixture of antibiotics of varying environmentally relevant concentrations (i.e., concentrations commonly encountered in wastewaters in order to investigate the effect of low levels of antibiotics on antibiotic resistance gene abundances and dynamics in a previously uncontaminated environment. Antibiotic concentrations were measured using liquid chromatography-tandem mass spectrometry. Abundances of seven antibiotic resistance genes and the class 1 integron integrase gene, intI1, were quantified using real-time PCR. Resistance genes sulI and ermB were quantified in the microcosm sediments with mean abundances 5 and 15 gene copies/10(6 16S rRNA gene copies, respectively. Class 1 integrons were determined in the sediments with a mean concentration of 3.8 × 10(4 copies/106 16S rRNA gene copies. The antibiotic treatment had no observable effect on antibiotic resistance gene or integron abundances.

  12. An Algorithm for the Stochastic Simulation of Gene Expression and Heterogeneous Population Dynamics

    CERN Document Server

    Charlebois, Daniel A; Fraser, Dawn; Kaern, Mads

    2011-01-01

    We present an algorithm for the stochastic simulation of gene expression and heterogeneous population dynamics. The algorithm combines an exact method to simulate molecular-level fluctuations in single cells and a constant-number Monte Carlo method to simulate time-dependent statistical characteristics of growing cell populations. To benchmark performance, we compare simulation results with steadystate and time-dependent analytical solutions for several scenarios, including steadystate and time-dependent gene expression, and the effects on population heterogeneity of cell growth, division, and DNA replication. This comparison demonstrates that the algorithm provides an efficient and accurate approach to simulate how complex biological features influence gene expression. We also use the algorithm to model gene expression dynamics within "bet-hedging" cell populations during their adaption to environmental stress. These simulations indicate that the algorithm provides a framework suitable for simulating and ana...

  13. Dynamic model of gene regulation for the lac operon

    Energy Technology Data Exchange (ETDEWEB)

    Angelova, Maia; Ben-Halim, Asma, E-mail: maia.angelova@northumbria.ac.uk, E-mail: asma.benhalim@northumbria.ac.uk [Intelligent Modelling Lab, School of Computing, Engineering and Information Sciences, Northumbria University, Newcastle upon Tyne NE2 1XE (United Kingdom)

    2011-03-01

    Gene regulatory network is a collection of DNA which interact with each other and with other matter in the cell. The lac operon is an example of a relatively simple genetic network and is one of the best-studied structures in the Escherichia coli bacteria. In this work we consider a deterministic model of the lac operon with a noise term, representing the stochastic nature of the regulation. The model is written in terms of a system of simultaneous first order differential equations with delays. We investigate an analytical and numerical solution and analyse the range of values for the parameters corresponding to a stable solution.

  14. Refining Dynamics of Gene Regulatory Networks in a Stochastic π-Calculus Framework

    OpenAIRE

    Paulevé, Loïc; Magnin, Morgan; Roux, Olivier

    2011-01-01

    International audience; In this paper, we introduce a framework allowing to model and analyse efficiently Gene Regulatory Networks in their temporal and stochastic aspects. The analysis of stable states and inference of René Thomas' discrete parameters derives from this logical formalism. We offer a compositional approach which comes with a natural translation to the Stochastic π-Calculus. The method we propose consists in successive refinements of generalized dynamics of Gene Regulatory Netw...

  15. Point-cycle bistability and stochasticity in a regulatory circuit for Bacillus subtilis competence.

    Science.gov (United States)

    Xi, Hongguang; Duan, Lixia; Turcotte, Marc

    2013-08-01

    Bacillus subtilis is a very well-studied organism in biology. Recent results show that an evolutionary plausible alternative competence regulation circuit for this bacterium, despite presenting equivalent functionality, exhibits physiologically important differences. Thus, it is not a priori clear why Nature only selects a specific gene regulation circuit other than a plethora of equivalent others. Here, we use simulations to study this question further. Based on the wild-type Bacillus subtilis circuit, we add a positive autoregulation feedback loop to the intermediate gene comS. We use bifurcation theory to study the dynamical features of the hypothetical gene circuit versus the feedback strength of the added loop, and we rely on stochastic simulations to perform in silico experiments. We discover the existence of a bistable system: a stable limit cycle and a stable fixed point separated by an unstable limit cycle with a varying height of underlying stochastic potential. This structure is absent from the wild type. The coexistence of the unstable limit cycle with stochastic noise endows the circuit with an ability to confine, prevent or switch between its two stable attractors.

  16. 一种高频动态磁滞回线的PSpice电路模型研究%Sduty for a PSpice-based circuit model of high frequency dynamic hysteresis loop

    Institute of Scientific and Technical Information of China (English)

    刘小军; 石玉; 赵宝林

    2011-01-01

    According to Jiles-Atherton ferromagnetic hysteresis theory and Hammerstein configuration we presented a Pspice circuit model of high frequency dynamic magnetic hysteresis loop. A Second-order low-pass filter has been inserted into the equivalent Pspice circuit of Jiles-Atherton mathematic model to capture the changes of magnetic hysteresis loop with frequency to analog the high frequency dynamic magnetic hysteresis loop approximately. The simulated magnetic hysteresis loop using this Pspice circuit model is preferably fitted with the measured result in frequency up to 300kHz.%根据Jiles-Atherton铁磁磁滞理论和Hammerstein结构宏模型提出了一种高频动态磁滞回线的PSpice电路模型.将二阶低通滤波器插入Jiles-Atherton数学模型的等效PSpice电路中,追踪磁滞回线随频率的变化,近似地模拟高频动态磁滞回线.经实验论证,用该PSpice电路模型仿真所得磁滞回线与实际测试结果在频率高达300kHz时仍然能较好符合.

  17. Solid-state circuits

    CERN Document Server

    Pridham, G J

    2013-01-01

    Solid-State Circuits provides an introduction to the theory and practice underlying solid-state circuits, laying particular emphasis on field effect transistors and integrated circuits. Topics range from construction and characteristics of semiconductor devices to rectification and power supplies, low-frequency amplifiers, sine- and square-wave oscillators, and high-frequency effects and circuits. Black-box equivalent circuits of bipolar transistors, physical equivalent circuits of bipolar transistors, and equivalent circuits of field effect transistors are also covered. This volume is divided

  18. Simple Autonomous Chaotic Circuits

    Science.gov (United States)

    Piper, Jessica; Sprott, J.

    2010-03-01

    Over the last several decades, numerous electronic circuits exhibiting chaos have been proposed. Non-autonomous circuits with as few as two components have been developed. However, the operation of such circuits relies on the non-ideal behavior of the devices used, and therefore the circuit equations can be quite complex. In this paper, we present two simple autonomous chaotic circuits using only opamps and linear passive components. The circuits each use one opamp as a comparator, to provide a signum nonlinearity. The chaotic behavior is robust, and independent of nonlinearities in the passive components. Moreover, the circuit equations are among the algebraically simplest chaotic systems yet constructed.

  19. Circuit analysis for dummies

    CERN Document Server

    Santiago, John

    2013-01-01

    Circuits overloaded from electric circuit analysis? Many universities require that students pursuing a degree in electrical or computer engineering take an Electric Circuit Analysis course to determine who will ""make the cut"" and continue in the degree program. Circuit Analysis For Dummies will help these students to better understand electric circuit analysis by presenting the information in an effective and straightforward manner. Circuit Analysis For Dummies gives you clear-cut information about the topics covered in an electric circuit analysis courses to help

  20. Current limiter circuit system

    Energy Technology Data Exchange (ETDEWEB)

    Witcher, Joseph Brandon; Bredemann, Michael V.

    2017-09-05

    An apparatus comprising a steady state sensing circuit, a switching circuit, and a detection circuit. The steady state sensing circuit is connected to a first, a second and a third node. The first node is connected to a first device, the second node is connected to a second device, and the steady state sensing circuit causes a scaled current to flow at the third node. The scaled current is proportional to a voltage difference between the first and second node. The switching circuit limits an amount of current that flows between the first and second device. The detection circuit is connected to the third node and the switching circuit. The detection circuit monitors the scaled current at the third node and controls the switching circuit to limit the amount of the current that flows between the first and second device when the scaled current is greater than a desired level.

  1. Synchronization Phenomena in Coupled Colpitts Circuits

    Directory of Open Access Journals (Sweden)

    Ch. K. Volos

    2014-11-01

    Full Text Available In this work, the case of coupling (bidirectional and unidirectional between two identical nonlinear chaotic circuits via a linear resistor, is studied. The produced dynamical systems have different structure, in regard to other similar works, due to the choice of coupling nodes. As a circuit, a modification of the most well-known nonlinear circuit that can operate in a wide range of radiofrequencies, the Colpitts oscillator, is chosen. The simulation and the experimental results show a variety of dynamical phenomena, such as periodic, quasi-periodic and chaotic behaviors, as well as anti-phase and complete synchronization phenomena, depending on the value of the coupling coefficient.

  2. Solenoid-Simulation Circuit

    Science.gov (United States)

    Simon, R. A.

    1986-01-01

    Electrical properties of solenoids imitated for tests of control circuits. Simulation circuit imitates voltage and current responses of two engine-controlling solenoids. Used in tests of programs of digital engine-control circuits, also provides electronic interface with circuits imitating electrical properties of pressure sensors and linear variable-differential transformers. Produces voltages, currents, delays, and discrete turnon and turnoff signals representing operation of solenoid in engine-control relay. Many such circuits used simulating overall engine circuitry.

  3. MicroRNA-mediated regulatory circuits: outlook and perspectives.

    Science.gov (United States)

    Cora', Davide; Re, Angela; Caselle, Michele; Bussolino, Federico

    2017-06-06

    MicroRNAs have been found to be necessary for regulating genes implicated in almost all signaling pathways, and consequently their dysfunction influences many diseases, including cancer. Understanding of the complexity of the microRNA-mediated regulatory network has grown in terms of size, connectivity and dynamics with the development of computational and, more recently, experimental high-throughput approaches for microRNA target identification. Newly developed studies on recurrent microRNA-mediated circuits in regulatory networks, also known as network motifs, have substantially contributed to addressing this complexity, and therefore to helping understand the ways by which microRNAs achieve their regulatory role. This review provides a summarizing view of the state-of-the-art, and perspectives of research efforts on microRNA-mediated regulatory motifs. In this review, we discuss the topological properties characterizing different types of circuits, and the regulatory features theoretically enabled by such properties, with a special emphasis on examples of circuits typifying their biological significance in experimentally validated contexts. Finally, we will consider possible future developments, in particular regarding microRNA-mediated circuits involving long non-coding RNAs and epigenetic regulators.

  4. Design of Nonlinear Circuits: The Linear Time-Varying Approach

    NARCIS (Netherlands)

    Kuijstermans, F.C.M.

    2003-01-01

    Over the last years the ever-growing demand for higher performance has led to much interest in using nonlinear circuit concepts for electronic circuit design. For this we have to deal with analysis and synthesis of dynamic nonlinear circuits. This thesis proposes to handle the nonlinear design

  5. Design of Nonlinear Circuits: The Linear Time-Varying Approach

    NARCIS (Netherlands)

    Kuijstermans, F.C.M.

    2003-01-01

    Over the last years the ever-growing demand for higher performance has led to much interest in using nonlinear circuit concepts for electronic circuit design. For this we have to deal with analysis and synthesis of dynamic nonlinear circuits. This thesis proposes to handle the nonlinear design comp

  6. Epigenetic phenomena, chromatin dynamics, and gene expression. New theoretical approaches in the study of living systems.

    Science.gov (United States)

    Boi, Luciano

    2008-01-01

    This paper is aimed at exploring the genome at the level beyond that of DNA sequence alone. We stress the fact that the level of genes is not the sole "reality" in the living world, for there are different epigenetic processes that profoundly affect change in living systems. Moreover, epigenetics very likely influences the course of evolution and the unfolding of life. We further attempt to investigate how the genome is dynamically organized into the nuclear space within the cell. We mainly focus on analyses of higher order nuclear architecture and the dynamic interactions of chromatin with other nuclear components. We especially want to know how epigenetic phenomena influences genes expression and chromosome functions. The proper understanding of these processes require new concepts and approaches be introduced and developed. In particular, we think that research in biology has to shift from only describing molecular and local features of living systems to studying the regulatory networks of interactions among gene pathways, the folding and dynamics of chromatin structure and how environmental factors affects the behavior of organisms. There are essential components of biological information on living organisms which cannot be portrayed in the DNA sequence alone. In a post-genomic era, the importance of chromatin/epigenetic interface has become increasingly apparent. One of the purposes of current research should be to highlight the enormous impact of chromatin organization and dynamics on epigenetic phenomena, and, conversely, to emphasize the important role that epigenetic phenomena play in gene expression and cell regulation.

  7. Colocalization of coregulated genes: a steered molecular dynamics study of human chromosome 19.

    Directory of Open Access Journals (Sweden)

    Marco Di Stefano

    Full Text Available The connection between chromatin nuclear organization and gene activity is vividly illustrated by the observation that transcriptional coregulation of certain genes appears to be directly influenced by their spatial proximity. This fact poses the more general question of whether it is at all feasible that the numerous genes that are coregulated on a given chromosome, especially those at large genomic distances, might become proximate inside the nucleus. This problem is studied here using steered molecular dynamics simulations in order to enforce the colocalization of thousands of knowledge-based gene sequences on a model for the gene-rich human chromosome 19. Remarkably, it is found that most (≈ 88% gene pairs can be brought simultaneously into contact. This is made possible by the low degree of intra-chromosome entanglement and the large number of cliques in the gene coregulatory network. A clique is a set of genes coregulated all together as a group. The constrained conformations for the model chromosome 19 are further shown to be organized in spatial macrodomains that are similar to those inferred from recent HiC measurements. The findings indicate that gene coregulation and colocalization are largely compatible and that this relationship can be exploited to draft the overall spatial organization of the chromosome in vivo. The more general validity and implications of these findings could be investigated by applying to other eukaryotic chromosomes the general and transferable computational strategy introduced here.

  8. Dynamics of Wolbachia pipientis Gene Expression Across the Drosophila melanogaster Life Cycle.

    Science.gov (United States)

    Gutzwiller, Florence; Carmo, Catarina R; Miller, Danny E; Rice, Danny W; Newton, Irene L G; Hawley, R Scott; Teixeira, Luis; Bergman, Casey M

    2015-10-23

    Symbiotic interactions between microbes and their multicellular hosts have manifold biological consequences. To better understand how bacteria maintain symbiotic associations with animal hosts, we analyzed genome-wide gene expression for the endosymbiotic α-proteobacteria Wolbachia pipientis across the entire life cycle of Drosophila melanogaster. We found that the majority of Wolbachia genes are expressed stably across the D. melanogaster life cycle, but that 7.8% of Wolbachia genes exhibit robust stage- or sex-specific expression differences when studied in the whole-organism context. Differentially-expressed Wolbachia genes are typically up-regulated after Drosophila embryogenesis and include many bacterial membrane, secretion system, and ankyrin repeat-containing proteins. Sex-biased genes are often organized as small operons of uncharacterized genes and are mainly up-regulated in adult Drosophila males in an age-dependent manner. We also systematically investigated expression levels of previously-reported candidate genes thought to be involved in host-microbe interaction, including those in the WO-A and WO-B prophages and in the Octomom region, which has been implicated in regulating bacterial titer and pathogenicity. Our work provides comprehensive insight into the developmental dynamics of gene expression for a widespread endosymbiont in its natural host context, and shows that public gene expression data harbor rich resources to probe the functional basis of the Wolbachia-Drosophila symbiosis and annotate the transcriptional outputs of the Wolbachia genome.

  9. Design of High-Performance 32 bit Adder with Semi-Dynamic Circuit%基于半动态电路的32位高性能加法器设计

    Institute of Scientific and Technical Information of China (English)

    刘志哲; 仲顺安; 袁家芬

    2011-01-01

    描述了一种采用半动态电路的32位高性能加法器的设计.设计中改进了现有稀疏树结构中的输出进位逻辑,在此基础上,设计了一种容偏斜多米诺和静态电路相结合的半动态电路,以及相应的多个控制时钟的时序策略.根据几种不同的加法器负载驱动情况,分别设计出不同的电路尺寸.采用SMIC 1.8 V 0.18 μm CMOS工艺,在不同条件下的仿真结果表明,加法器电路取得了良好的性能.%This paper presents a programme of designing 32 bit high-performance adder with semidynamic circuit. With modified output carry logic in sparse-tree structure, the semi-dynamic adder circuit, which includes skew-tolerant dynamic domino-circuit and static circuit, and its multiple clocks timing scheme were designed. The different transistor's sizes of adder were designed to fit the different loads and drive conditions of the adder. In SMIC 1.8 V 0. 18 μm technology, the simulation results under different conditions show that the designed adder has a high performance.

  10. Expression dynamics of secreted protease genes in Trichophyton rubrum induced by key host's proteinaceous components.

    Science.gov (United States)

    Leng, Wenchuan; Liu, Tao; Wang, Jin; Li, Ruoyu; Jin, Qi

    2009-11-01

    Trichophyton rubrum is the most common agent of dermatophytosis, a disease that affects millions of individuals worldwide. Its molecular pathogenicity mechanisms are still not completely elucidated. It has been widely recognized that proteases secreted by T. rubrum are the key virulence factors during host infection. However, our knowledge about the expression of its secreted proteases in host infection is still obscure. This investigation provides the expression patterns and dynamics of secreted protease genes belonging to the subtilisins (SUB) and metalloproteases (MEP) gene families in T. rubrum. The data was obtained under simulated host infection conditions through relative quantification of real time PCR. Keratin, collagen, and elastin induced the expression of similar protease genes, and the expression patterns and dynamics of these protease genes in media containing human skin sections were different from those in media containing individual protein substrates. According to the expression dynamics of these protease genes, we conclude that Sub3, Sub4, and Mep4 may be the dominant proteases secreted by T. rubrum during host infection, and that these proteases could be good targets for new antifungal chemotherapy and molecular diagnostic markers. This work presents useful molecular details to further our understanding of the pathogenesis of dermatophytosis.

  11. A model for computing genes governing marital dissolution through sentimental dynamics.

    Science.gov (United States)

    Zhou, Linghua; Shen, Yong; Wu, Weimiao; Wang, Zuoheng; Hou, Wei; Zhu, Sheng; Wu, Rongling

    2014-07-21

    Adverse sentimental relationships that cause marital dissolution may involve a genetic component composed of genes from a couple, which interact with cultural, sociological, psychological and economic factors. However, the identification of these genes is very challenging. Here, we address this challenge by developing a computational model that can identify specific genes that impact on sentimental relationships of couples. The model was derived by implementing the second law of thermodynamics that quantifies sentimental relationships within a dynamic gene identification framework, called systems mapping. The model is equipped with a capacity to characterize and test the pattern of how genes from a couple interact with each other to determine the dynamic behavior of their marital relationships. The testing procedure is based on comparing genotypic differences in mathematical parameters of sentimental dynamics described by a group of ordinary differential equations (ODE). The model allows the test of individual parameters or a combination of parameters, addressing specific details related to martial relationships. The model may find its implications for designing an optimal effort policy and therapy to maintain a harmonic family in light of genetic blueprints of individual couples.

  12. Fabrication of Al/AlOx/Al Josephson junctions and superconducting quantum circuits by shadow evaporation and a dynamic oxidation process

    Institute of Scientific and Technical Information of China (English)

    Wu Yu-Lin; Deng Hui; Yu Hai-Feng; Xue Guang-Ming; Tian Ye; Li Jie; Chen Ying-Fei

    2013-01-01

    Besides serving as promising candidates for realizing quantum computing,superconducting quantum circuits are one of a few macroscopic physical systems in which fundamental quantum phenomena can be directly demonstrated and tested,giving rise to a vast field of intensive research work both theoretically and experimentally.In this paper we report our work on the fabrication of superconducting quantum circuits,starting from its building blocks:Al/AlOx/Al Josephson junctions.By using electron beam lithography patterning and shadow evaporation,we have fabricated aluminum Josephson junctions with a controllable critical current density (jc) and wide range of junction sizes from 0.01 μm2 up to 1 μm2.We have carried out systematical studies on the oxidation process in fabricating Al/AlOx/Al Josephson junctions suitable for superconducting flux qubits.Furthermore,we have also fabricated superconducting quantum circuits such as superconducting flux qubits and charge-flux qubits.

  13. CircuitsDB: a database of mixed microRNA/transcription factor feed-forward regulatory circuits in human and mouse

    Directory of Open Access Journals (Sweden)

    Friard Olivier

    2010-08-01

    Full Text Available Abstract Background Transcription Factors (TFs and microRNAs (miRNAs are key players for gene expression regulation in higher eukaryotes. In the last years, a large amount of bioinformatic studies were devoted to the elucidation of transcriptional and post-transcriptional (mostly miRNA-mediated regulatory interactions, but little is known about the interplay between them. Description Here we describe a dynamic web-accessible database, CircuitsDB, supporting a genome-wide transcriptional and post-transcriptional regulatory network integration, for the human and mouse genomes, based on a bioinformatic sequence-analysis approach. In particular, CircuitsDB is currently focused on the study of mixed miRNA/TF Feed-Forward regulatory Loops (FFLs, i.e. elementary circuits in which a master TF regulates an miRNA and together with it a set of Joint Target protein-coding genes. The database was constructed using an ab-initio oligo analysis procedure for the identification of the transcriptional and post-transcriptional interactions. Several external sources of information were then pooled together to obtain the functional annotation of the proposed interactions. Results for human and mouse genomes are presented in an integrated web tool, that allows users to explore the circuits, investigate their sequence and functional properties and thus suggest possible biological experiments. Conclusions We present CircuitsDB, a web-server devoted to the study of human and mouse mixed miRNA/TF Feed-Forward regulatory circuits, freely available at: http://biocluster.di.unito.it/circuits/

  14. Quantitative transcription dynamic analysis reveals candidate genes and key regulators for ethanol tolerance in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ma, Menggen; Liu, Lewis Z

    2010-06-10

    Derived from our lignocellulosic conversion inhibitor-tolerant yeast, we generated an ethanol-tolerant strain Saccharomyces cerevisiae NRRL Y-50316 by enforced evolutionary adaptation. Using a newly developed robust mRNA reference and a master equation unifying gene expression data analyses, we investigated comparative quantitative transcription dynamics of 175 genes selected from previous studies for an ethanol-tolerant yeast and its closely related parental strain. A highly fitted master equation was established and applied for quantitative gene expression analyses using pathway-based qRT-PCR array assays. The ethanol-tolerant Y-50316 displayed significantly enriched background of mRNA abundance for at least 35 genes without ethanol challenge compared with its parental strain Y-50049. Under the ethanol challenge, the tolerant Y-50316 responded in consistent expressions over time for numerous genes belonging to groups of heat shock proteins, trehalose metabolism, glycolysis, pentose phosphate pathway, fatty acid metabolism, amino acid biosynthesis, pleiotropic drug resistance gene family and transcription factors. The parental strain showed repressed expressions for many genes and was unable to withstand the ethanol stress and establish a viable culture and fermentation. The distinct expression dynamics between the two strains and their close association with cell growth, viability and ethanol fermentation profiles distinguished the tolerance-response from the stress-response in yeast under the ethanol challenge. At least 82 genes were identified as candidate and key genes for ethanol-tolerance and subsequent fermentation under the stress. Among which, 36 genes were newly recognized by the present study. Most of the ethanol-tolerance candidate genes were found to share protein binding motifs of transcription factors Msn4p/Msn2p, Yap1p, Hsf1p and Pdr1p/Pdr3p. Enriched background of transcription abundance and enhanced expressions of ethanol-tolerance genes

  15. Quantitative transcription dynamic analysis reveals candidate genes and key regulators for ethanol tolerance in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Ma Menggen

    2010-06-01

    Full Text Available Abstract Background Derived from our lignocellulosic conversion inhibitor-tolerant yeast, we generated an ethanol-tolerant strain Saccharomyces cerevisiae NRRL Y-50316 by enforced evolutionary adaptation. Using a newly developed robust mRNA reference and a master equation unifying gene expression data analyses, we investigated comparative quantitative transcription dynamics of 175 genes selected from previous studies for an ethanol-tolerant yeast and its closely related parental strain. Results A highly fitted master equation was established and applied for quantitative gene expression analyses using pathway-based qRT-PCR array assays. The ethanol-tolerant Y-50316 displayed significantly enriched background of mRNA abundance for at least 35 genes without ethanol challenge compared with its parental strain Y-50049. Under the ethanol challenge, the tolerant Y-50316 responded in consistent expressions over time for numerous genes belonging to groups of heat shock proteins, trehalose metabolism, glycolysis, pentose phosphate pathway, fatty acid metabolism, amino acid biosynthesis, pleiotropic drug resistance gene family and transcription factors. The parental strain showed repressed expressions for many genes and was unable to withstand the ethanol stress and establish a viable culture and fermentation. The distinct expression dynamics between the two strains and their close association with cell growth, viability and ethanol fermentation profiles distinguished the tolerance-response from the stress-response in yeast under the ethanol challenge. At least 82 genes were identified as candidate and key genes for ethanol-tolerance and subsequent fermentation under the stress. Among which, 36 genes were newly recognized by the present study. Most of the ethanol-tolerance candidate genes were found to share protein binding motifs of transcription factors Msn4p/Msn2p, Yap1p, Hsf1p and Pdr1p/Pdr3p. Conclusion Enriched background of transcription abundance

  16. Hidden circuits and argumentation

    Science.gov (United States)

    Leinonen, Risto; Kesonen, Mikko H. P.; Hirvonen, Pekka E.

    2016-11-01

    Despite the relevance of DC circuits in everyday life and schools, they have been shown to cause numerous learning difficulties at various school levels. In the course of this article, we present a flexible method for teaching DC circuits at lower secondary level. The method is labelled as hidden circuits, and the essential idea underlying hidden circuits is in hiding the actual wiring of DC circuits, but to make their behaviour evident for pupils. Pupils are expected to find out the wiring of the circuit which should enhance their learning of DC circuits. We present two possible ways to utilise hidden circuits in a classroom. First, they can be used to test and enhance pupils’ conceptual understanding when pupils are expected to find out which one of the offered circuit diagram options corresponds to the actual circuit shown. This method aims to get pupils to evaluate the circuits holistically rather than locally, and as a part of that aim this method highlights any learning difficulties of pupils. Second, hidden circuits can be used to enhance pupils’ argumentation skills with the aid of argumentation sheet that illustrates the main elements of an argument. Based on the findings from our co-operating teachers and our own experiences, hidden circuits offer a flexible and motivating way to supplement teaching of DC circuits.

  17. Dynamic Analysis of Gene Expression in Rice Superior and Inferior Grains by RNA-Seq

    Science.gov (United States)

    Sun, Hongzheng; Peng, Ting; Zhao, Yafan; Du, Yanxiu; Zhang, Jing; Li, Junzhou; Xin, Zeyu; Zhao, Quanzhi

    2015-01-01

    Poor grain filling of inferior grains located on lower secondary panicle branch causes great drop in rice yield and quality. Dynamic gene expression patterns between superior and inferior grains were examined from the view of the whole transcriptome by using RNA-Seq method. In total, 19,442 genes were detected during rice grain development. Genes involved in starch synthesis, grain storage and grain development were interrogated in particular in superior and inferior grains. Of the genes involved in sucrose to starch transformation process, most were expressed at lower level in inferior grains at early filling stage compared to that of superior grains. But at late filling stage, the expression of those genes was higher in inferior grains and lower in superior grains. The same trends were observed in the expression of grain storage protein genes. While, evidence that genes involved in cell cycle showed higher expression in inferior grains during whole period of grain filling indicated that cell proliferation was active till the late filling stage. In conclusion, delayed expression of most starch synthesis genes in inferior grains and low capacity of sink organ might be two important factors causing low filling rate of inferior grain at early filling stage, and shortage of carbohydrate supply was a limiting factor at late filling stage. PMID:26355995

  18. Temporal dynamics of gene expression in the lung in a baboon model of E. coli sepsis

    Directory of Open Access Journals (Sweden)

    Zhu Hua

    2007-02-01

    Full Text Available Abstract Background Bacterial invasion during sepsis induces disregulated systemic responses that could lead to fatal lung failure. The purpose of this study was to relate the temporal dynamics of gene expression to the pathophysiological changes in the lung during the first and second stages of E. coli sepsis in baboons. Results Using human oligonucleotide microarrays, we have explored the temporal changes of gene expression in the lung of baboons challenged with sublethal doses of E. coli. Temporal expression pattern and biological significance of the differentially expressed genes were explored using clustering and pathway analysis software. Expression of selected genes was validated by real-time PCR. Cytokine levels in tissue and plasma were assayed by multiplex ELISA. Changes in lung ultrastructure were visualized by electron microscopy. We found that genes involved in primary inflammation, innate immune response, and apoptosis peaked at 2 hrs. Inflammatory and immune response genes that function in the stimulation of monocytes, natural killer and T-cells, and in the modulation of cell adhesion peaked at 8 hrs, while genes involved in wound healing and functional recovery were upregulated at 24 hrs. Conclusion The analysis of gene expression modulation in response to sepsis provides the baseline information that is crucial for the understanding of the pathophysiology of systemic inflammation and may facilitate the development of future approaches for sepsis therapy.

  19. Dynamic regulatory interactions of Polycomb group genes: MEDEA autoregulation is required for imprinted gene expression in Arabidopsis.

    Science.gov (United States)

    Baroux, Célia; Gagliardini, Valeria; Page, Damian R; Grossniklaus, Ueli

    2006-05-01

    The imprinted Arabidopsis Polycomb group (PcG) gene MEDEA (MEA), which is homologous to Enhancer of Zeste [E(Z)], is maternally required for normal seed development. Here we show that, unlike known mammalian imprinted genes, MEA regulates its own imprinted expression: It down-regulates the maternal allele around fertilization and maintains the paternal allele silent later during seed development. Autorepression of the maternal MEA allele is direct and independent of the MEA-FIE (FERTILIZATION-INDEPENDENT ENDOSPERM) PcG complex, which is similar to the E(Z)-ESC (Extra sex combs) complex of animals, suggesting a novel mechanism. A complex network of cross-regulatory interactions among the other known members of the MEA-FIE PcG complex implies distinct functions that are dynamically regulated during reproduction.

  20. Intuitive analog circuit design

    CERN Document Server

    Thompson, Marc

    2013-01-01

    Intuitive Analog Circuit Design outlines ways of thinking about analog circuits and systems that let you develop a feel for what a good, working analog circuit design should be. This book reflects author Marc Thompson's 30 years of experience designing analog and power electronics circuits and teaching graduate-level analog circuit design, and is the ideal reference for anyone who needs a straightforward introduction to the subject. In this book, Dr. Thompson describes intuitive and ""back-of-the-envelope"" techniques for designing and analyzing analog circuits, including transistor amplifi

  1. The circuit designer's companion

    CERN Document Server

    Williams, Tim

    2013-01-01

    The Circuit Designer's Companion covers the theoretical aspects and practices in analogue and digital circuit design. Electronic circuit design involves designing a circuit that will fulfill its specified function and designing the same circuit so that every production model of it will fulfill its specified function, and no other undesired and unspecified function.This book is composed of nine chapters and starts with a review of the concept of grounding, wiring, and printed circuits. The subsequent chapters deal with the passive and active components of circuitry design. These topics are foll

  2. Design of Low Power CMOS Circuits using Leakage Control Transistor and Multi-Threshold CMOS Techniques

    OpenAIRE

    2012-01-01

    The scaling down of technology in CMOS circuits, results in the down scaling of threshold voltage thereby increasing the sub-threshold leakage current. An IC consists of many circuits of which some circuits consists critical path like full adder, whereas some circuits like multiplexer and decoder has no specified critical path. LECTOR is a technique for designing leakage power reduced CMOS circuits without affecting the dynamic power dissipation, which can be used for circuits with no specifi...

  3. Dynamic gene expression in fish muscle during recovery growth induced by a fasting-refeeding schedule

    Directory of Open Access Journals (Sweden)

    Esquerré Diane

    2007-11-01

    Full Text Available Abstract Background Recovery growth is a phase of rapid growth that is triggered by adequate refeeding of animals following a period of weight loss caused by starvation. In this study, to obtain more information on the system-wide integration of recovery growth in muscle, we undertook a time-course analysis of transcript expression in trout subjected to a food deprivation-refeeding sequence. For this purpose complex targets produced from muscle of trout fasted for one month and from muscle of trout fasted for one month and then refed for 4, 7, 11 and 36 days were hybridized to cDNA microarrays containing 9023 clones. Results Significance analysis of microarrays (SAM and temporal expression profiling led to the segregation of differentially expressed genes into four major clusters. One cluster comprising 1020 genes with high expression in muscle from fasted animals included a large set of genes involved in protein catabolism. A second cluster that included approximately 550 genes with transient induction 4 to 11 days post-refeeding was dominated by genes involved in transcription, ribosomal biogenesis, translation, chaperone activity, mitochondrial production of ATP and cell division. A third cluster that contained 480 genes that were up-regulated 7 to 36 days post-refeeding was enriched with genes involved in reticulum and Golgi dynamics and with genes indicative of myofiber and muscle remodelling such as genes encoding sarcomeric proteins and matrix compounds. Finally, a fourth cluster of 200 genes overexpressed only in 36-day refed trout muscle contained genes with function in carbohydrate metabolism and lipid biosynthesis. Remarkably, among the genes induced were several transcriptional regulators which might be important for the gene-specific transcriptional adaptations that underlie muscle recovery. Conclusion Our study is the first demonstration of a coordinated expression of functionally related genes during muscle recovery growth

  4. Measuring fast gene dynamics in single cells with time-lapse luminescence microscopy

    Science.gov (United States)

    Mazo-Vargas, Anyimilehidi; Park, Heungwon; Aydin, Mert; Buchler, Nicolas E.

    2014-01-01

    Time-lapse fluorescence microscopy is an important tool for measuring in vivo gene dynamics in single cells. However, fluorescent proteins are limited by slow chromophore maturation times and the cellular autofluorescence or phototoxicity that arises from light excitation. An alternative is luciferase, an enzyme that emits photons and is active upon folding. The photon flux per luciferase is significantly lower than that for fluorescent proteins. Thus time-lapse luminescence microscopy has been successfully used to track gene dynamics only in larger organisms and for slower processes, for which more total photons can be collected in one exposure. Here we tested green, yellow, and red beetle luciferases and optimized substrate conditions for in vivo luminescence. By combining time-lapse luminescence microscopy with a microfluidic device, we tracked the dynamics of cell cycle genes in single yeast with subminute exposure times over many generations. Our method was faster and in cells with much smaller volumes than previous work. Fluorescence of an optimized reporter (Venus) lagged luminescence by 15–20 min, which is consistent with its known rate of chromophore maturation in yeast. Our work demonstrates that luciferases are better than fluorescent proteins at faithfully tracking the underlying gene expression. PMID:25232010

  5. Dynamic gene expression for metabolic engineering of mammalian cells in culture.

    Science.gov (United States)

    Le, Huong; Vishwanathan, Nandita; Kantardjieff, Anne; Doo, Inseok; Srienc, Michael; Zheng, Xiaolu; Somia, Nikunj; Hu, Wei-Shou

    2013-11-01

    Recombinant mammalian cells are the major hosts for the production of protein therapeutics. In addition to high expression of the product gene, a hyper-producer must also harbor superior phenotypic traits related to metabolism, protein secretion, and growth control. Introduction of genes endowing the relevant hyper-productivity traits is a strategy frequently used to enhance the productivity. Most of such cell engineering efforts have been performed using constitutive expression systems. However, cells respond to various environmental cues and cellular events dynamically according to cellular needs. The use of inducible systems allows for time dependent expression, but requires external manipulation. Ideally, a transgene's expression should be synchronous to the host cell's own rhythm, and at levels appropriate for the objective. To that end, we identified genes with different expression dynamics and intensity ranges using pooled transcriptome data. Their promoters may be used to drive the expression of the transgenes following the desired dynamics. We isolated the promoter of the Thioredoxin-interacting protein (Txnip) gene and demonstrated its capability to drive transgene expression in concert with cell growth. We further employed this Chinese hamster promoter to engineer dynamic expression of the mouse GLUT5 fructose transporter in Chinese hamster ovary (CHO) cells, enabling them to utilize sugar according to cellular needs rather than in excess as typically seen in culture. Thus, less lactate was produced, resulting in a better growth rate, prolonged culture duration, and higher product titer. This approach illustrates a novel concept in metabolic engineering which can potentially be used to achieve dynamic control of cellular behaviors for enhanced process characteristics.

  6. 动态自适应遗传算法在模拟电路中的应用%Dynamic Adaptive Genetic Algorithm in the Application of the Analog Circuits

    Institute of Scientific and Technical Information of China (English)

    王硕

    2016-01-01

    In order to resolve the problems of parameter adjustment in analog circuit design , by combination of analog design with genetic algorithm , this paper proposes a dynamic adaptive genetic algorithm as the op-amp method of analog circuit design , so as to obtain the op-amp best parameters in analog circuit by adding the op -amp parameters to the improvement of the genetic algo-rithm.%针对在模拟电路设计中参数调整出现的问题,将模拟电路设计与遗传算法相结合,提出一种利用动态自适应遗传算法设计模拟电路的运放的方法。通过将运放参数融入到遗传算法的改进中,实现模拟电路中运放的参数最佳。

  7. Matlab在二阶动态电路实验教学中的三种应用%Study of Matlab Simulation Teaching for Second-Order Dynamic Circuit

    Institute of Scientific and Technical Information of China (English)

    张丽萍; 朱尧富

    2013-01-01

    Second-order dynamic circuit is highly theoretical and complex in response, it's difficult to realize effective teaching. Because of the powerful function of Matlab, it can be used in the circuit calculation and simulation to improve working efficiency greatly, and provide help in the teaching for both “teaching” and “learning”. At first, analysis of the zero input response of second-order dynamic circuit is carried out, and the discharging process and characteristics for four situations are introduced, then the zero input response of a same second-order circuit in under-damped situation is simulated using Simulink, Matlab programming and GUI method, getting analytic solutions and numerical solutions. Through the comparison for the three methods the advantages of Matlab in circuit analysis are introduced, which has strong versatility and high efficiency used in teaching.%  二阶动态电路的分析理论性很强,响应情况复杂,难以实现有效教学。利用Matlab强大的功能进行电路计算和仿真,能大大提高工作效率,应用于教学中对“教”与“学”都有很大帮助。首先对二阶动态电路零输入响应进行理论分析,介绍四种情况放电过程及特点,然后分别用Simulink仿真、Matlab编程仿真、GUI仿真三种方法对同一个欠阻尼情况下二阶电路零输入响应进行仿真,得到响应解析解和数值解,通过三种方法的实践对比,介绍Matlab软件在动态电路分析方面的优越性,应用于教学通用性强,效率高。

  8. Reconstructing a network of stress-response regulators via dynamic system modeling of gene regulation.

    Science.gov (United States)

    Wu, Wei-Sheng; Li, Wen-Hsiung; Chen, Bor-Sen

    2008-02-10

    Unicellular organisms such as yeasts have evolved mechanisms to respond to environmental stresses by rapidly reorganizing the gene expression program. Although many stress-response genes in yeast have been discovered by DNA microarrays, the stress-response transcription factors (TFs) that regulate these stress-response genes remain to be investigated. In this study, we use a dynamic system model of gene regulation to describe the mechanism of how TFs may control a gene's expression. Then, based on the dynamic system model, we develop the Stress Regulator Identification Algorithm (SRIA) to identify stress-response TFs for six kinds of stresses. We identified some general stress-response TFs that respond to various stresses and some specific stress-response TFs that respond to one specific stress. The biological significance of our findings is validated by the literature. We found that a small number of TFs is probably sufficient to control a wide variety of expression patterns in yeast under different stresses. Two implications can be inferred from this observation. First, the response mechanisms to different stresses may have a bow-tie structure. Second, there may be regulatory cross-talks among different stress responses. In conclusion, this study proposes a network of stress-response regulators and the details of their actions.

  9. Interplay of Noisy Gene Expression and Dynamics Explains Patterns of Bacterial Operon Organization

    Science.gov (United States)

    Igoshin, Oleg

    2011-03-01

    Bacterial chromosomes are organized into operons -- sets of genes co-transcribed into polycistronic messenger RNA. Hypotheses explaining the emergence and maintenance of operons include proportional co-regulation, horizontal transfer of intact ``selfish'' operons, emergence via gene duplication, and co-production of physically interacting proteins to speed their association. We hypothesized an alternative: operons can reduce or increase intrinsic gene expression noise in a manner dependent on the post-translational interactions, thereby resulting in selection for or against operons in depending on the network architecture. We devised five classes of two-gene network modules and show that the effects of operons on intrinsic noise depend on class membership. Two classes exhibit decreased noise with co-transcription, two others reveal increased noise, and the remaining one does not show a significant difference. To test our modeling predictions we employed bioinformatic analysis to determine the relationship gene expression noise and operon organization. The results confirm the overrepresentation of noise-minimizing operon architectures and provide evidence against other hypotheses. Our results thereby suggest a central role for gene expression noise in selecting for or maintaining operons in bacterial chromosomes. This demonstrates how post-translational network dynamics may provide selective pressure for organizing bacterial chromosomes, and has practical consequences for designing synthetic gene networks. This work is supported by National Institutes of Health grant 1R01GM096189-01.

  10. Electrical Circuits and Water Analogies

    Science.gov (United States)

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  11. JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade.

    Directory of Open Access Journals (Sweden)

    Pedro B Pinto

    2015-07-01

    Full Text Available Organogenesis is controlled by gene networks activated by upstream selector genes. During development the gene network is activated stepwise, with a sequential deployment of successive transcription factors and signalling molecules that modify the interaction of the elements of the network as the organ forms. Very little is known about the steps leading from the early specification of the cells that form the organ primordium to the moment when a robust gene network is in place. Here we study in detail how a Hox protein induces during early embryogenesis a simple organogenetic cascade that matures into a complex gene network through the activation of feedback and feed forward interaction loops. To address how the network organization changes during development and how the target genes integrate the genetic information it provides, we analyze in Drosophila the induction of posterior spiracle organogenesis by the Hox gene Abdominal-B (Abd-B. Initially, Abd-B activates in the spiracle primordium a cascade of transcription factors and signalling molecules including the JAK/STAT signalling pathway. We find that at later stages STAT activity feeds back directly into Abd-B, initiating the transformation of the Hox cascade into a gene-network. Focusing on crumbs, a spiracle downstream target gene of Abd-B, we analyze how a modular cis regulatory element integrates the dynamic network information set by Abd-B and the JAK/STAT signalling pathway during development. We describe how a Hox induced genetic cascade transforms into a robust gene network during organogenesis due to the repeated interaction of Abd-B and one of its targets, the JAK/STAT signalling cascade. Our results show that in this network STAT functions not just as a direct transcription factor, but also acts as a "counter-repressor", uncovering a novel mode for STAT directed transcriptional regulation.

  12. JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade

    Science.gov (United States)

    Pinto, Pedro B.; Espinosa-Vázquez, Jose Manuel; Rivas, María Luísa; Hombría, James Castelli-Gair

    2015-01-01

    Organogenesis is controlled by gene networks activated by upstream selector genes. During development the gene network is activated stepwise, with a sequential deployment of successive transcription factors and signalling molecules that modify the interaction of the elements of the network as the organ forms. Very little is known about the steps leading from the early specification of the cells that form the organ primordium to the moment when a robust gene network is in place. Here we study in detail how a Hox protein induces during early embryogenesis a simple organogenetic cascade that matures into a complex gene network through the activation of feedback and feed forward interaction loops. To address how the network organization changes during development and how the target genes integrate the genetic information it provides, we analyze in Drosophila the induction of posterior spiracle organogenesis by the Hox gene Abdominal-B (Abd-B). Initially, Abd-B activates in the spiracle primordium a cascade of transcription factors and signalling molecules including the JAK/STAT signalling pathway. We find that at later stages STAT activity feeds back directly into Abd-B, initiating the transformation of the Hox cascade into a gene-network. Focusing on crumbs, a spiracle downstream target gene of Abd-B, we analyze how a modular cis regulatory element integrates the dynamic network information set by Abd-B and the JAK/STAT signalling pathway during development. We describe how a Hox induced genetic cascade transforms into a robust gene network during organogenesis due to the repeated interaction of Abd-B and one of its targets, the JAK/STAT signalling cascade. Our results show that in this network STAT functions not just as a direct transcription factor, but also acts as a "counter-repressor", uncovering a novel mode for STAT directed transcriptional regulation. PMID:26230388

  13. Circuits on Cylinders

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt; Miltersen, Peter Bro; Vinay, V

    2006-01-01

    We consider the computational power of constant width polynomial size cylindrical circuits and nondeterministic branching programs. We show that every function computed by a Pi2 o MOD o AC0 circuit can also be computed by a constant width polynomial size cylindrical nondeterministic branching...... program (or cylindrical circuit) and that every function computed by a constant width polynomial size cylindrical circuit belongs to ACC0....

  14. Electric circuits essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electric Circuits I includes units, notation, resistive circuits, experimental laws, transient circuits, network theorems, techniques of circuit analysis, sinusoidal analysis, polyph

  15. Control theory applied to the design of AGC circuits

    OpenAIRE

    Bertran Albertí, Eduardo; Palacin, J M

    1991-01-01

    Applications of control theory in the design of automatic gain control (AGC) circuits are presented. A general model for AGC circuits is presented, and an equivalent linear system is proposed. Its behavior is compared with the dynamical response of two implemented AGC circuits. The results of classic and state variable correctors based on the model are presented. These results show the usefulness of this linear model in the design of the AGC dynamic response. By using a linear and t-variant s...

  16. Synthetic analog and digital circuits for cellular computation and memory

    OpenAIRE

    Purcell, Oliver; Lu, Timothy K.

    2014-01-01

    Biological computation is a major area of focus in synthetic biology because it has the potential to enable a wide range of applications. Synthetic biologists have applied engineering concepts to biological systems in order to construct progressively more complex gene circuits capable of processing information in living cells. Here, we review the current state of computational genetic circuits and describe artificial gene circuits that perform digital and analog computation. We then discuss r...

  17. Piezoelectric drive circuit

    Science.gov (United States)

    Treu, Jr., Charles A.

    1999-08-31

    A piezoelectric motor drive circuit is provided which utilizes the piezoelectric elements as oscillators and a Meacham half-bridge approach to develop feedback from the motor ground circuit to produce a signal to drive amplifiers to power the motor. The circuit automatically compensates for shifts in harmonic frequency of the piezoelectric elements due to pressure and temperature changes.

  18. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2010-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital converte

  19. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2011-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital converte

  20. Load testing circuit

    DEFF Research Database (Denmark)

    2009-01-01

    A load testing circuit a circuit tests the load impedance of a load connected to an amplifier. The load impedance includes a first terminal and a second terminal, the load testing circuit comprising a signal generator providing a test signal of a defined bandwidth to the first terminal of the load...

  1. Short-circuit logic

    NARCIS (Netherlands)

    Bergstra, J.A.; Ponse, A.

    2010-01-01

    Short-circuit evaluation denotes the semantics of propositional connectives in which the second argument is only evaluated if the first argument does not suffice to determine the value of the expression. In programming, short-circuit evaluation is widely used. A short-circuit logic is a variant of p

  2. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, Simon Minze; Vertregt, Maarten

    2011-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital converte

  3. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, Simon Minze; Vertregt, Maarten

    2010-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital converte

  4. Global transgenerational gene expression dynamics in two newly synthesized allohexaploid wheat (Triticum aestivum lines

    Directory of Open Access Journals (Sweden)

    Qi Bao

    2012-01-01

    Full Text Available Abstract Background Alteration in gene expression resulting from allopolyploidization is a prominent feature in plants, but its spectrum and extent are not fully known. Common wheat (Triticum aestivum was formed via allohexaploidization about 10,000 years ago, and became the most important crop plant. To gain further insights into the genome-wide transcriptional dynamics associated with the onset of common wheat formation, we conducted microarray-based genome-wide gene expression analysis on two newly synthesized allohexaploid wheat lines with chromosomal stability and a genome constitution analogous to that of the present-day common wheat. Results Multi-color GISH (genomic in situ hybridization was used to identify individual plants from two nascent allohexaploid wheat lines between Triticum turgidum (2n = 4x = 28; genome BBAA and Aegilops tauschii (2n = 2x = 14; genome DD, which had a stable chromosomal constitution analogous to that of common wheat (2n = 6x = 42; genome BBAADD. Genome-wide analysis of gene expression was performed for these allohexaploid lines along with their parental plants from T. turgidum and Ae. tauschii, using the Affymetrix Gene Chip Wheat Genome-Array. Comparison with the parental plants coupled with inclusion of empirical mid-parent values (MPVs revealed that whereas the great majority of genes showed the expected parental additivity, two major patterns of alteration in gene expression in the allohexaploid lines were identified: parental dominance expression and non-additive expression. Genes involved in each of the two altered expression patterns could be classified into three distinct groups, stochastic, heritable and persistent, based on their transgenerational heritability and inter-line conservation. Strikingly, whereas both altered patterns of gene expression showed a propensity of inheritance, identity of the involved genes was highly stochastic, consistent with the involvement of diverse Gene Ontology (GO

  5. Experimental assessment of static and dynamic algorithms for gene regulation inference from time series expression data

    Directory of Open Access Journals (Sweden)

    Miguel eLopes

    2013-12-01

    Full Text Available Accurate inference of causal gene regulatory networks from gene expression data is an open bioinformatics challenge. Gene interactions are dynamical processes and consequently we can expect that the effect of any regulation action occurs after a certain temporal lag. However such lag is unknown a priori and temporal aspects require specific inference algorithms. In this paper we aim to assess the impact of taking into consideration temporal aspects on the final accuracy of the inference procedure. In particular we will compare the accuracy of static algorithms, where no dynamic aspect is considered, to that of fixed lag and adaptive lag algorithms in three inference tasks from microarray expression data. Experimental results show that network inference algorithms that take dynamics into account perform consistently better than static ones, once the considered lags are properly chosen. However, no individual algorithm stands out in all three inference tasks, and the challenging nature of network inference tasks is evidenced, as a large number of the assessed algorithms does not perform better than random.

  6. Dynamic changes in protein functional linkage networks revealed by integration with gene expression data.

    Directory of Open Access Journals (Sweden)

    Shubhada R Hegde

    2008-11-01

    Full Text Available Response of cells to changing environmental conditions is governed by the dynamics of intricate biomolecular interactions. It may be reasonable to assume, proteins being the dominant macromolecules that carry out routine cellular functions, that understanding the dynamics of protein:protein interactions might yield useful insights into the cellular responses. The large-scale protein interaction data sets are, however, unable to capture the changes in the profile of protein:protein interactions. In order to understand how these interactions change dynamically, we have constructed conditional protein linkages for Escherichia coli by integrating functional linkages and gene expression information. As a case study, we have chosen to analyze UV exposure in wild-type and SOS deficient E. coli at 20 minutes post irradiation. The conditional networks exhibit similar topological properties. Although the global topological properties of the networks are similar, many subtle local changes are observed, which are suggestive of the cellular response to the perturbations. Some such changes correspond to differences in the path lengths among the nodes of carbohydrate metabolism correlating with its loss in efficiency in the UV treated cells. Similarly, expression of hubs under unique conditions reflects the importance of these genes. Various centrality measures applied to the networks indicate increased importance for replication, repair, and other stress proteins for the cells under UV treatment, as anticipated. We thus propose a novel approach for studying an organism at the systems level by integrating genome-wide functional linkages and the gene expression data.

  7. Dynamic Stability Analysis and Comparison between Single and Double Breakers of Air Circuit Breaker%双断点与单断点万能式断路器电动稳定性的分析与对比

    Institute of Scientific and Technical Information of China (English)

    陈德桂

    2009-01-01

    提出了一种新型双断点万能式断路器.以两个简化的模型,在短路电流作用下,分析了双断点和单断点万能式断路器触头上的电动斥力,对比了双断点和单断点万能式断路器触头上的电动稳定性,说明了双断点结构具有高电动稳定性的原因.指出提高操作机构的机械强度是双断点万能式断路器设计的关键.%A new dual-breaker air circuit breaker(ACB)was proposed.With two simplified model suffering the effect of short circuit current,the dynamic repulsion force acted on contact in ACB with single and double breakers were analyzed and compared.The reason that dual-breaker configuration had higher dynamic stability was explained as well.The key design of ACB is to impmve the mechanical strength of operation mechanism.

  8. Correlation of Dynamic PET and Gene Array Data in Patients with Gastrointestinal Stromal Tumors

    Directory of Open Access Journals (Sweden)

    Ludwig G. Strauss

    2012-01-01

    Full Text Available Introduction. The results obtained with dynamic PET (dPET were compared to gene expression data obtained in patients with gastrointestinal stromal tumors (GIST. The primary aim was to assess the association of the dPET results and gene expression data. Material and Methods. dPET was performed following the injection of F-18-fluorodeoxyglucose (FDG in 22 patients with GIST. All patients were examined prior to surgery for staging purpose. Compartment and noncompartment models were used for the quantitative evaluation of the dPET examinations. Gene array data were based on tumor specimen obtained by surgery after the PET examinations. Results. The data analysis revealed significant correlations for the dPET parameters and the expression of zinc finger genes (znf43, znf85, znf91, znf189. Furthermore, the transport of FDG (k1 was associated with VEGF-A. The cell cycle gene cyclin-dependent kinase inhibitor 1C was correlated with the maximum tracer uptake (SUVmax in the tumors. Conclusions. The data demonstrate a dependency of the tracer kinetics on genes associated with prognosis in GIST. Furthermore, angiogenesis and cell proliferation have an impact on the tracer uptake.

  9. Evolutionary dynamics of a conserved sequence motif in the ribosomal genes of the ciliate Paramecium

    Directory of Open Access Journals (Sweden)

    Lynch Michael

    2010-05-01

    Full Text Available Abstract Background In protozoa, the identification of preserved motifs by comparative genomics is often impeded by difficulties to generate reliable alignments for non-coding sequences. Moreover, the evolutionary dynamics of regulatory elements in 3' untranslated regions (both in protozoa and metazoa remains a virtually unexplored issue. Results By screening Paramecium tetraurelia's 3' untranslated regions for 8-mers that were previously found to be preserved in mammalian 3' UTRs, we detect and characterize a motif that is distinctly conserved in the ribosomal genes of this ciliate. The motif appears to be conserved across Paramecium aurelia species but is absent from the ribosomal genes of four additional non-Paramecium species surveyed, including another ciliate, Tetrahymena thermophila. Motif-free ribosomal genes retain fewer paralogs in the genome and appear to be lost more rapidly relative to motif-containing genes. Features associated with the discovered preserved motif are consistent with this 8-mer playing a role in post-transcriptional regulation. Conclusions Our observations 1 shed light on the evolution of a putative regulatory motif across large phylogenetic distances; 2 are expected to facilitate the understanding of the modulation of ribosomal genes expression in Paramecium; and 3 reveal a largely unexplored--and presumably not restricted to Paramecium--association between the presence/absence of a DNA motif and the evolutionary fate of its host genes.

  10. Reversible Logic Circuit Synthesis

    CERN Document Server

    Shende, V V; Markov, I L; Prasad, A K; Hayes, John P.; Markov, Igor L.; Prasad, Aditya K.; Shende, Vivek V.

    2002-01-01

    Reversible, or information-lossless, circuits have applications in digital signal processing, communication, computer graphics and cryptography. They are also a fundamental requirement for quantum computation. We investigate the synthesis of reversible circuits that employ a minimum number of gates and contain no redundant input-output line-pairs (temporary storage channels). We propose new constructions for reversible circuits composed of NOT, Controlled-NOT, and TOFFOLI gates (the CNT gate library) based on permutation theory. A new algorithm is given to synthesize optimal reversible circuits using an arbitrary gate library. We also describe much faster heuristic algorithms. We also pursue applications of the proposed techniques to the synthesis of quantum circuits.

  11. 真空断路器新型电机操动机构的多体动力学仿真%Multi-Body Dynamics Simulation and Analysis on Novel Motor-Operating Mechanism for Vacuum Circuit Breakers

    Institute of Scientific and Technical Information of China (English)

    林莘; 宋立峰; 李永祥; 徐建源

    2012-01-01

    To improve the reliability of circuit breakers, a new motor-operating mechanism, which possesses such advantages as simple structure, small size, fast response and controllable moving process, is developed. The focal point of the research is concentrated to the switching on/off characteristics of vacuum circuit breaker with motor-operating mechanism. Taking a 40.5kV vacuum circuit breaker with motor operating mechanism as research object and using automatic dynamic analysis of mechanical systems (ADAMS), a virtral prototype model of vacuum circuit breaker with a new type of motor-operating mechanism is built to simulate the switching on/off processes of the circuit breaker. From simulation results corresponding relation between the rotated angle of the motor and the stroke of the contact of circuit breaker as well as the characteristics of contact stroke and speed vs time during the switching on/off process are obtained. Meanwhile, the experiments of switching on/off of the vacuum circuit breaker are made and the corresponding moving characteristics are measured by the torque sensor installed on the rotating shaft and the displacement sensor installed on insulating tension pole. Contrastive analysis on results from experiments and simulation shows that the output characteristics of the simulation model can well conform to experiment results, thus it also states clearly that the virtual prototype model is effective.%为提高断路器的可靠性,研究了一种新型的电机机构,该电机机构具有结构简单、体积小、响应快且运动过程可控等优点,研究重点为在电机机构操作下真空断路器的分广合闸机械特性。结合40.5kV配电机机构的真空断路器,采用多体动力学仿真软件(automatic dynamic analysis of mechanicai systems,ADAMS)建立真空断路器新型电机机构的虚拟样机模型,对断路器的分/合闸过程进行仿真分析。由动态仿真得到电机转角与动触头

  12. GENE EXPRESSION DYNAMICS IN PATIENTS WITH SEVERE THERAPY-RESISTANT ASTHMA DURING TREATMENT PERIOD

    Directory of Open Access Journals (Sweden)

    Ye. S. Kulikov

    2014-01-01

    Full Text Available Introduction: The leading mechanisms and causes of severe therapy resistant asthma are poorly understood. The aim of this study was to define global patterns of gene expression in adults with severe therapy-resistant asthma in dynamic during treatment period.Methods: Performed 24-week prospective interventional study in parallel groups. Severe asthma patients was aposterior divided at therapy sensitive and resistant patients according to ATS criteria. Global transcriptome profile was characterized using the Affymetrix HuGene ST1.0 chip. Cluster analysis was performed.Results and conclusion: According to our data several mechanisms of therapy resistance may be considered: increased levels of nitric oxide and beta2-agonists nitration, dysregulation of endogenous steroids secretion and involvement in the pathogenesis of Staphylococcus aureus. Absence of suppression of gene expression KEGG-pathway “asthma" may reflect the low efficiency or long period of anti-inflammatory therapy effect realization.

  13. Reconstructing a Network of Stress-Response Regulators via Dynamic System Modeling of Gene Regulation

    Directory of Open Access Journals (Sweden)

    Wei-Sheng Wu

    2008-01-01

    Full Text Available Unicellular organisms such as yeasts have evolved mechanisms to respond to environmental stresses by rapidly reorganizing the gene expression program. Although many stress-response genes in yeast have been discovered by DNA microarrays, the stress-response transcription factors (TFs that regulate these stress-response genes remain to be investigated. In this study, we use a dynamic system model of gene regulation to describe the mechanism of how TFs may control a gene’s expression. Then, based on the dynamic system model, we develop the Stress Regulator Identification Algorithm (SRIA to identify stress-response TFs for six kinds of stresses. We identified some general stress-response TFs that respond to various stresses and some specific stress-response TFs that respond to one specifi c stress. The biological significance of our findings is validated by the literature. We found that a small number of TFs is probably suffi cient to control a wide variety of expression patterns in yeast under different stresses. Two implications can be inferred from this observation. First, the response mechanisms to different stresses may have a bow-tie structure. Second, there may be regulatory cross-talks among different stress responses. In conclusion, this study proposes a network of stress-response regulators and the details of their actions.

  14. Theory of circuit block switch-off

    Directory of Open Access Journals (Sweden)

    S. Henzler

    2004-01-01

    Full Text Available Switching-off unused circuit blocks is a promising approach to supress static leakage currents in ultra deep sub-micron CMOS digital systems. Basic performance parameters of Circuit Block Switch-Off (CBSO schemes are defined and their dependence on basic circuit parameters is estimated. Therefore the design trade-off between strong leakage suppression in idle mode and adequate dynamic performance in active mode can be supported by simple analytic investigations. Additionally, a guideline for the estimation of the minimum time for which a block deactivation is useful is derived.

  15. Maximum Temperature Detection System for Integrated Circuits

    Science.gov (United States)

    Frankiewicz, Maciej; Kos, Andrzej

    2015-03-01

    The paper describes structure and measurement results of the system detecting present maximum temperature on the surface of an integrated circuit. The system consists of the set of proportional to absolute temperature sensors, temperature processing path and a digital part designed in VHDL. Analogue parts of the circuit where designed with full-custom technique. The system is a part of temperature-controlled oscillator circuit - a power management system based on dynamic frequency scaling method. The oscillator cooperates with microprocessor dedicated for thermal experiments. The whole system is implemented in UMC CMOS 0.18 μm (1.8 V) technology.

  16. Solution methods for very highly integrated circuits.

    Energy Technology Data Exchange (ETDEWEB)

    Nong, Ryan; Thornquist, Heidi K.; Chen, Yao; Mei, Ting; Santarelli, Keith R.; Tuminaro, Raymond Stephen

    2010-12-01

    While advances in manufacturing enable the fabrication of integrated circuits containing tens-to-hundreds of millions of devices, the time-sensitive modeling and simulation necessary to design these circuits poses a significant computational challenge. This is especially true for mixed-signal integrated circuits where detailed performance analyses are necessary for the individual analog/digital circuit components as well as the full system. When the integrated circuit has millions of devices, performing a full system simulation is practically infeasible using currently available Electrical Design Automation (EDA) tools. The principal reason for this is the time required for the nonlinear solver to compute the solutions of large linearized systems during the simulation of these circuits. The research presented in this report aims to address the computational difficulties introduced by these large linearized systems by using Model Order Reduction (MOR) to (i) generate specialized preconditioners that accelerate the computation of the linear system solution and (ii) reduce the overall dynamical system size. MOR techniques attempt to produce macromodels that capture the desired input-output behavior of larger dynamical systems and enable substantial speedups in simulation time. Several MOR techniques that have been developed under the LDRD on 'Solution Methods for Very Highly Integrated Circuits' will be presented in this report. Among those presented are techniques for linear time-invariant dynamical systems that either extend current approaches or improve the time-domain performance of the reduced model using novel error bounds and a new approach for linear time-varying dynamical systems that guarantees dimension reduction, which has not been proven before. Progress on preconditioning power grid systems using multi-grid techniques will be presented as well as a framework for delivering MOR techniques to the user community using Trilinos and the Xyce circuit

  17. Exact Threshold Circuits

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt; Podolskii, Vladimir V.

    2010-01-01

    We initiate a systematic study of constant depth Boolean circuits built using exact threshold gates. We consider both unweighted and weighted exact threshold gates and introduce corresponding circuit classes. We next show that this gives a hierarchy of classes that seamlessly interleave with the ......We initiate a systematic study of constant depth Boolean circuits built using exact threshold gates. We consider both unweighted and weighted exact threshold gates and introduce corresponding circuit classes. We next show that this gives a hierarchy of classes that seamlessly interleave...... with the well-studied corresponding hierarchies defined using ordinary threshold gates. A major open problem in Boolean circuit complexity is to provide an explicit super-polynomial lower bound for depth two threshold circuits. We identify the class of depth two exact threshold circuits as a natural subclass...

  18. Feedback in analog circuits

    CERN Document Server

    Ochoa, Agustin

    2016-01-01

    This book describes a consistent and direct methodology to the analysis and design of analog circuits with particular application to circuits containing feedback. The analysis and design of circuits containing feedback is generally presented by either following a series of examples where each circuit is simplified through the use of insight or experience (someone else’s), or a complete nodal-matrix analysis generating lots of algebra. Neither of these approaches leads to gaining insight into the design process easily. The author develops a systematic approach to circuit analysis, the Driving Point Impedance and Signal Flow Graphs (DPI/SFG) method that does not require a-priori insight to the circuit being considered and results in factored analysis supporting the design function. This approach enables designers to account fully for loading and the bi-directional nature of elements both in the feedback path and in the amplifier itself, properties many times assumed negligible and ignored. Feedback circuits a...

  19. The Dynamical Topological Models of Lagrange’s and Hamiltonian Equations for Complex Nonlinear Electrical Circuit System%复杂非线性电路系统的动力学方程模型

    Institute of Scientific and Technical Information of China (English)

    欧松

    2012-01-01

    Lagrange和Hamilton运动方程是分析力学的基本原理之一和方法论.应用Lagrange和Hamilton原理建立复杂非线性电路保守动力学方程模型是一种形式化可行的方法.对非保守的动力学系统,定义描述电路系统的荷控支路和链控支路的微观结构概念,应用Hamilton结构的方法,可以得到与Lagrange结构等价的方程组;考虑大规模电路系统的复杂性,依据电路系统荷控支路和链控支路微观结构的概念,给出具有控制参量的Lagrange和Hamilton函数,以及具有相应关联矩阵和联接矩阵形式的Lagrange和Hamilton的动态方程;分析了保守和非保守复杂系统拓扑结构关系的描述和其动力学系统的建模,其建模过程具有规范性和方程具有对称性.虽然数学推导过程繁琐,但适合于计算机辅助形式化分析;基于Hamilton方法建立的电路模型为一阶微分动态方程组,特别适合进行理论分析和数值仿真计算.%The Lagrange's and Hamiltonian movement equation are one of the basic principles of analytical mechanics and methodology. The application of Lagrange's and Hamiltonian theory approach to modeling complex nonlinear conservation electrical circuits dynamics system is a practicable in formulation methodology. But for the non conservation electrical circuits dynamics system, a new micro structure conception of electric charge quantitative control branch and magnetic chain control branch in electrical circuit system has been put forward that have equality with the Lagrange's equations; Consideration of the topological complexity of large electrical circuit system, based on the micro structure conception of electric charge quantitative control branch and magnetic chain control branch in electrical circuit, and the Lagrange's and Hamiltonian function that have control parameters are given. ; as well as the Lagrange's and Hamiltonian equations that have incidence matrix and linked matrix; So the

  20. Dynamic evolution of the GnRH receptor gene family in vertebrates.

    Science.gov (United States)

    Williams, Barry L; Akazome, Yasuhisa; Oka, Yoshitaka; Eisthen, Heather L

    2014-10-25

    Elucidating the mechanisms underlying coevolution of ligands and receptors is an important challenge in molecular evolutionary biology. Peptide hormones and their receptors are excellent models for such efforts, given the relative ease of examining evolutionary changes in genes encoding for both molecules. Most vertebrates possess multiple genes for both the decapeptide gonadotropin releasing hormone (GnRH) and for the GnRH receptor. The evolutionary history of the receptor family, including ancestral copy number and timing of duplications and deletions, has been the subject of controversy. We report here for the first time sequences of three distinct GnRH receptor genes in salamanders (axolotls, Ambystoma mexicanum), which are orthologous to three GnRH receptors from ranid frogs. To understand the origin of these genes within the larger evolutionary context of the gene family, we performed phylogenetic analyses and probabilistic protein homology searches of GnRH receptor genes in vertebrates and their near relatives. Our analyses revealed four points that alter previous views about the evolution of the GnRH receptor gene family. First, the "mammalian" pituitary type GnRH receptor, which is the sole GnRH receptor in humans and previously presumed to be highly derived because it lacks the cytoplasmic C-terminal domain typical of most G-protein coupled receptors, is actually an ancient gene that originated in the common ancestor of jawed vertebrates (Gnathostomata). Second, unlike previous studies, we classify vertebrate GnRH receptors into five subfamilies. Third, the order of subfamily origins is the inverse of previous proposed models. Fourth, the number of GnRH receptor genes has been dynamic in vertebrates and their ancestors, with multiple duplications and losses. Our results provide a novel evolutionary framework for generating hypotheses concerning the functional importance of structural characteristics of vertebrate GnRH receptors. We show that five

  1. Qualitative and quantitative stability analysis of penta-rhythmic circuits

    Science.gov (United States)

    Schwabedal, Justus T. C.; Knapper, Drake E.; Shilnikov, Andrey L.

    2016-12-01

    Inhibitory circuits of relaxation oscillators are often-used models for dynamics of biological networks. We present a qualitative and quantitative stability analysis of such a circuit constituted by three generic oscillators (of a Fitzhugh-Nagumo type) as its nodes coupled reciprocally. Depending on inhibitory strengths, and parameters of individual oscillators, the circuit exhibits polyrhythmicity of up to five simultaneously stable rhythms. With methods of bifurcation analysis and phase reduction, we investigate qualitative changes in stability of these circuit rhythms for a wide range of parameters. Furthermore, we quantify robustness of the rhythms maintained under random perturbations by monitoring phase diffusion in the circuit. Our findings allow us to describe how circuit dynamics relate to dynamics of individual nodes. We also find that quantitative and qualitative stability properties of polyrhythmicity do not always align.

  2. Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals.

    Science.gov (United States)

    Niimura, Yoshihito; Matsui, Atsushi; Touhara, Kazushige

    2014-09-01

    Olfactory receptors (ORs) detect odors in the environment, and OR genes constitute the largest multigene family in mammals. Numbers of OR genes vary greatly among species--reflecting the respective species' lifestyles--and this variation is caused by frequent gene gains and losses during evolution. However, whether the extent of gene gains/losses varies among individual gene lineages and what might generate such variation is unknown. To answer these questions, we used a newly developed phylogeny-based method to classify >10,000 intact OR genes from 13 placental mammal species into 781 orthologous gene groups (OGGs); we then compared the OGGs. Interestingly, African elephants had a surprisingly large repertoire (∼ 2000) of functional OR genes encoded in enlarged gene clusters. Additionally, OR gene lineages that experienced more gene duplication had weaker purifying selection, and Class II OR genes have evolved more dynamically than those in Class I. Some OGGs were highly expanded in a lineage-specific manner, while only three OGGs showed complete one-to-one orthology among the 13 species without any gene gains/losses. These three OGGs also exhibited highly conserved amino acid sequences; therefore, ORs in these OGGs may have physiologically important functions common to every placental mammal. This study provides a basis for inferring OR functions from evolutionary trajectory. © 2014 Niimura et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency

    Institute of Scientific and Technical Information of China (English)

    R David Hawkins; Zhen Ye; Samantha Kuan; Pengzhi Yu; Hui Liu; Xinmin Zhang; Roland D Green; Victor V Lobanenkov; Ron Stewart; James A Thomson; Bing Ren; Gary C Hon; Chuhu Yang; Jessica E Antosiewicz-Bourget; LeonardKLee; Que-Minh Ngo; Sarit Klugman; Keith A Ching; Lee E Edsall

    2011-01-01

    Pluripotency,the ability of a cell to differentiate and give rise to all embryonic lineages,defines a small number of mammalian cell types such as embryonic stem (ES) cells.While it has been generally held that pluripotency is the product of a transcriptional regulatory network that activates and maintains the expression of key stem cell genes,accumulating evidence is pointing to a critical role for epigenetic processes in establishing and safeguarding the pluripotency of ES cells,as well as maintaining the identity of differentiated cell types.In order to better understand the role of epigenetic mechanisms in pluripotency,we have examined the dynamics of chromatin modifications genomewide in human ES cells (hESCs) undergoing differentiation into a mesendodermal lineage.We found that chromatin modifications at promoters remain largely invariant during differentiation,except at a small number of promoters where a dynamic switch between acetylation and methylation at H3K27 marks the transition between activation and silencing of gene expression,suggesting a hierarchy in cell fate commitment over most differentially expressed genes.We also mapped over 50 000 potential enhancers,and observed much greater dynamics in chromatin modifications,especially H3K4mel and H3K27ac,which correlate with expression of their potential target genes.Further analysis of these enhancers revealed potentially key transcriptional regulators of pluripotency and a chromatin signature indicative of a poised state that may confer developmental competence in hESCs.Our results provide new evidence supporting the role of chromatin modifications in defining enhancers and pluripotency.

  4. The Dynamics of Lateral Gene Transfer in Genus Leishmania - A Route for Adaptation and Species Diversification.

    Science.gov (United States)

    Vikeved, Elisabet; Backlund, Anders; Alsmark, Cecilia

    2016-01-01

    The genome of Leishmania major harbours a comparably high proportion of genes of prokaryote origin, acquired by lateral gene transfer (LGT). Some of these are present in closely related trypanosomatids, while some are detected in Leishmania only. We have evaluated the impact and destiny of LGT in genus Leishmania. To study the dynamics and fate of LGTs we have performed phylogenetic, as well as nucleotide and amino acid composition analyses within orthologous groups of LGTs detected in Leishmania. A set of universal trypanosomatid LGTs was added as a reference group. Both groups of LGTs have, to some extent, ameliorated to resemble the recipient genomes. However, while virtually all of the universal trypanosomatid LGTs are distributed and conserved in the entire genus Leishmania, the LGTs uniquely present in genus Leishmania are more prone to gene loss and display faster rates of evolution. Furthermore, a PCR based approach has been employed to ascertain the presence of a set of twenty LGTs uniquely present in genus Leishmania, and three universal trypanosomatid LGTs, in ten additional strains of Leishmania. Evolutionary rates and predicted expression levels of these LGTs have also been estimated. Ten of the twenty LGTs are distributed and conserved in all species investigated, while the remainder have been subjected to modifications, or undergone pseudogenization, degradation or loss in one or more species. LGTs unique to the genus Leishmania have been acquired after the divergence of Leishmania from the other trypanosomatids, and are evolving faster than their recipient genomes. This implies that LGT in genus Leishmania is a continuous and dynamic process contributing to species differentiation and speciation. This study also highlights the importance of carefully evaluating these dynamic genes, e.g. as LGTs have been suggested as potential drug targets.

  5. A modular positive feedback-based gene amplifier

    Directory of Open Access Journals (Sweden)

    Bhalerao Kaustubh D

    2010-02-01

    Full Text Available Abstract Background Positive feedback is a common mechanism used in the regulation of many gene circuits as it can amplify the response to inducers and also generate binary outputs and hysteresis. In the context of electrical circuit design, positive feedback is often considered in the design of amplifiers. Similar approaches, therefore, may be used for the design of amplifiers in synthetic gene circuits with applications, for example, in cell-based sensors. Results We developed a modular positive feedback circuit that can function as a genetic signal amplifier, heightening the sensitivity to inducer signals as well as increasing maximum expression levels without the need for an external cofactor. The design utilizes a constitutively active, autoinducer-independent variant of the quorum-sensing regulator LuxR. We experimentally tested the ability of the positive feedback module to separately amplify the output of a one-component tetracycline sensor and a two-component aspartate sensor. In each case, the positive feedback module amplified the response to the respective inducers, both with regards to the dynamic range and sensitivity. Conclusions The advantage of our design is that the actual feedback mechanism depends only on a single gene and does not require any other modulation. Furthermore, this circuit can amplify any transcriptional signal, not just one encoded within the circuit or tuned by an external inducer. As our design is modular, it can potentially be used as a component in the design of more complex synthetic gene circuits.

  6. Dynamics of simple gene-network motifs subject to extrinsic fluctuations

    Science.gov (United States)

    Roberts, Elijah; Be'er, Shay; Bohrer, Chris; Sharma, Rati; Assaf, Michael

    2015-12-01

    Cellular processes do not follow deterministic rules; even in identical environments genetically identical cells can make random choices leading to different phenotypes. This randomness originates from fluctuations present in the biomolecular interaction networks. Most previous work has been focused on the intrinsic noise (IN) of these networks. Yet, especially for high-copy-number biomolecules, extrinsic or environmental noise (EN) has been experimentally shown to dominate the variation. Here, we develop an analytical formalism that allows for calculation of the effect of EN on gene-expression motifs. We introduce a method for modeling bounded EN as an auxiliary species in the master equation. The method is fully generic and is not limited to systems with small EN magnitudes. We focus our study on motifs that can be viewed as the building blocks of genetic switches: a nonregulated gene, a self-inhibiting gene, and a self-promoting gene. The role of the EN properties (magnitude, correlation time, and distribution) on the statistics of interest are systematically investigated, and the effect of fluctuations in different reaction rates is compared. Due to its analytical nature, our formalism can be used to quantify the effect of EN on the dynamics of biochemical networks and can also be used to improve the interpretation of data from single-cell gene-expression experiments.

  7. Regulatory circuit for responses of nitrogen catabolic gene expression to the GLN3 and DAL80 proteins and nitrogen catabolite repression in Saccharomyces cerevisiae.

    OpenAIRE

    Daugherty, J R; Rai, R; el Berry, H M; Cooper, T. G.

    1993-01-01

    We demonstrate that expression of the UGA1, CAN1, GAP1, PUT1, PUT2, PUT4, and DAL4 genes is sensitive to nitrogen catabolite repression. The expression of all these genes, with the exception of UGA1 and PUT2, also required a functional GLN3 protein. In addition, GLN3 protein was required for expression of the DAL1, DAL2, DAL7, GDH1, and GDH2 genes. The UGA1, CAN1, GAP1, and DAL4 genes markedly increased their expression when the DAL80 locus, encoding a negative regulatory element, was disrupt...

  8. ‘Candidatus Accumulibacter' gene expression in response to dynamic EBPR conditions

    Science.gov (United States)

    He, Shaomei; McMahon, Katherine D

    2011-01-01

    Enhanced biological phosphorus removal (EBPR) activated sludge communities enriched in ‘Candidatus Accumulibacter' relatives are widely used in wastewater treatment, but much remains to be learned about molecular-level controls on the EBPR process. The expression of genes found in the carbon and polyphosphate metabolic pathways in Accumulibacter was investigated using reverse transcription quantitative PCR. During a normal anaerobic/aerobic EBPR cycle, gene expression exhibited a dynamic change in response to external acetate, oxygen, phosphate concentrations and probably internal chemical pools. Anaerobic acetate addition induced expression of genes associated with the methylmalonyl-CoA pathway enabling the split mode of the tricarboxylic acid (TCA) cycle. Components of the full TCA cycle were induced after the switch to aerobic conditions. The induction of a key gene in the glyoxylate shunt pathway was observed under both anaerobic and aerobic conditions, with a higher induction by aeration. Polyphosphate kinase 1 from Accumulibacter was expressed, but did not appear to be regulated by phosphate limitation. To understand how Accumulibacter responds to disturbed electron donor and acceptor conditions, we perturbed the process by adding acetate aerobically. When high concentrations of oxygen were present simultaneously with acetate, phosphate-release was almost completely inhibited, and polyphosphate kinase 1 transcript abundance decreased. Genes associated with the methylmalonyl-CoA pathway were repressed and genes associated with the aerobic TCA cycle exhibited higher expression under this perturbation, suggesting that more acetyl-CoA was metabolized through the TCA cycle. These findings suggest that several genes involved in EBPR are tightly regulated at the transcriptional level. PMID:20703317

  9. Validation of IRS PCR, a molecular typing method, for the study of the diversity and population dynamics of Legionella in industrial cooling circuits.

    Science.gov (United States)

    Jakubek, D; Le Brun, M; Leblon, G; Dubow, M; Binet, M

    2013-02-01

    Legionella bacteria are ubiquitous in aquatic environments. Members of the species Legionella pneumophila are responsible for more than 98% of cases of Legionnaires' disease in France. Our objective was to validate a molecular typing method called infrequent restriction site PCR (IRS PCR), applied to the study of the ecology of Legionella and to compare this method with reference typing methods, pulsed-field gel electrophoresis (PFGE) and sequence-based Typing (SBT). PFGE and SBT are considered as gold methods for the epidemiological typing of Leg. pneumophila strains. However, these methods are not suitable to an ecological monitoring of Legionella in natural environments where a large number of strains has to be typed. Validation of IRS PCR method was performed by the identification of 45 Leg. pneumophila isolates from cooling circuits of thermal power plants by IRS PCR, PFGE and SBT. The parameters of each method were measured and compared to evaluate the effectiveness of IRS PCR. The results of this study showed that IRS PCR has a discriminating power similar or better than that of the reference methods and thus that, by its speed and low cost represents an appropriate tool for the study of the ecology of Legionella in cooling circuits.

  10. Phonon waveguides for electromechanical circuits

    Science.gov (United States)

    Hatanaka, D.; Mahboob, I.; Onomitsu, K.; Yamaguchi, H.

    2014-07-01

    Nanoelectromechanical systems (NEMS), utilizing localized mechanical vibrations, have found application in sensors, signal processors and in the study of macroscopic quantum mechanics. The integration of multiple mechanical elements via electrical or optical means remains a challenge in the realization of NEMS circuits. Here, we develop a phonon waveguide using a one-dimensional array of suspended membranes that offers purely mechanical means to integrate isolated NEMS resonators. We demonstrate that the phonon waveguide can support and guide mechanical vibrations and that the periodic membrane arrangement also creates a phonon bandgap that enables control of the phonon propagation velocity. Furthermore, embedding a phonon cavity into the phonon waveguide allows mobile mechanical vibrations to be dynamically switched or transferred from the waveguide to the cavity, thereby illustrating the viability of waveguide-resonator coupling. These highly functional traits of the phonon waveguide architecture exhibit all the components necessary to permit the realization of all-phononic NEMS circuits.

  11. Complex and dynamic patterns of Wnt pathway gene expression in the developing chick forebrain

    Directory of Open Access Journals (Sweden)

    Lumsden Andrew

    2009-09-01

    Full Text Available Abstract Background Wnt signalling regulates multiple aspects of brain development in vertebrate embryos. A large number of Wnts are expressed in the embryonic forebrain; however, it is poorly understood which specific Wnt performs which function and how they interact. Wnts are able to activate different intracellular pathways, but which of these pathways become activated in different brain subdivisions also remains enigmatic. Results We have compiled the first comprehensive spatiotemporal atlas of Wnt pathway gene expression at critical stages of forebrain regionalisation in the chick embryo and found that most of these genes are expressed in strikingly dynamic and complex patterns. Several expression domains do not respect proposed compartment boundaries in the developing forebrain, suggesting that areal identities are more dynamic than previously thought. Using an in ovo electroporation approach, we show that Wnt4 expression in the thalamus is negatively regulated by Sonic hedgehog (Shh signalling from the zona limitans intrathalamica (ZLI, a known organising centre of forebrain development. Conclusion The forebrain is exposed to a multitude of Wnts and Wnt inhibitors that are expressed in a highly dynamic and complex fashion, precluding simple correlative conclusions about their respective functions or signalling mechanisms. In various biological systems, Wnts are antagonised by Shh signalling. By demonstrating that Wnt4 expression in the thalamus is repressed by Shh from the ZLI we reveal an additional level of interaction between these two pathways and provide an example for the cross-regulation between patterning centres during forebrain regionalisation.

  12. Robust design of biological circuits: evolutionary systems biology approach.

    Science.gov (United States)

    Chen, Bor-Sen; Hsu, Chih-Yuan; Liou, Jing-Jia

    2011-01-01

    Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise.

  13. Regenerative feedback resonant circuit

    Science.gov (United States)

    Jones, A. Mark; Kelly, James F.; McCloy, John S.; McMakin, Douglas L.

    2014-09-02

    A regenerative feedback resonant circuit for measuring a transient response in a loop is disclosed. The circuit includes an amplifier for generating a signal in the loop. The circuit further includes a resonator having a resonant cavity and a material located within the cavity. The signal sent into the resonator produces a resonant frequency. A variation of the resonant frequency due to perturbations in electromagnetic properties of the material is measured.

  14. Analog circuit design

    CERN Document Server

    Dobkin, Bob

    2012-01-01

    Analog circuit and system design today is more essential than ever before. With the growth of digital systems, wireless communications, complex industrial and automotive systems, designers are being challenged to develop sophisticated analog solutions. This comprehensive source book of circuit design solutions aids engineers with elegant and practical design techniques that focus on common analog challenges. The book's in-depth application examples provide insight into circuit design and application solutions that you can apply in today's demanding designs. <

  15. Parallelizing quantum circuit synthesis

    OpenAIRE

    Di Matteo, Olivia; Mosca, Michele

    2016-01-01

    Quantum circuit synthesis is the process in which an arbitrary unitary operation is decomposed into a sequence of gates from a universal set, typically one which a quantum computer can implement both efficiently and fault-tolerantly. As physical implementations of quantum computers improve, the need is growing for tools which can effectively synthesize components of the circuits and algorithms they will run. Existing algorithms for exact, multi-qubit circuit synthesis scale exponentially in t...

  16. Analog circuits cookbook

    CERN Document Server

    Hickman, Ian

    2013-01-01

    Analog Circuits Cookbook presents articles about advanced circuit techniques, components and concepts, useful IC for analog signal processing in the audio range, direct digital synthesis, and ingenious video op-amp. The book also includes articles about amplitude measurements on RF signals, linear optical imager, power supplies and devices, and RF circuits and techniques. Professionals and students of electrical engineering will find the book informative and useful.

  17. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

    DEFF Research Database (Denmark)

    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    ) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...

  18. Electronic devices and circuits

    CERN Document Server

    Pridham, Gordon John

    1968-01-01

    Electronic Devices and Circuits, Volume 1 deals with the design and applications of electronic devices and circuits such as passive components, diodes, triodes and transistors, rectification and power supplies, amplifying circuits, electronic instruments, and oscillators. These topics are supported with introductory network theory and physics. This volume is comprised of nine chapters and begins by explaining the operation of resistive, inductive, and capacitive elements in direct and alternating current circuits. The theory for some of the expressions quoted in later chapters is presented. Th

  19. CMOS circuits manual

    CERN Document Server

    Marston, R M

    1995-01-01

    CMOS Circuits Manual is a user's guide for CMOS. The book emphasizes the practical aspects of CMOS and provides circuits, tables, and graphs to further relate the fundamentals with the applications. The text first discusses the basic principles and characteristics of the CMOS devices. The succeeding chapters detail the types of CMOS IC, including simple inverter, gate and logic ICs and circuits, and complex counters and decoders. The last chapter presents a miscellaneous collection of two dozen useful CMOS circuits. The book will be useful to researchers and professionals who employ CMOS circu

  20. Circuits and filters handbook

    CERN Document Server

    Chen, Wai-Kai

    2003-01-01

    A bestseller in its first edition, The Circuits and Filters Handbook has been thoroughly updated to provide the most current, most comprehensive information available in both the classical and emerging fields of circuits and filters, both analog and digital. This edition contains 29 new chapters, with significant additions in the areas of computer-aided design, circuit simulation, VLSI circuits, design automation, and active and digital filters. It will undoubtedly take its place as the engineer's first choice in looking for solutions to problems encountered in the design, analysis, and behavi

  1. Timergenerator circuits manual

    CERN Document Server

    Marston, R M

    2013-01-01

    Timer/Generator Circuits Manual is an 11-chapter text that deals mainly with waveform generator techniques and circuits. Each chapter starts with an explanation of the basic principles of its subject followed by a wide range of practical circuit designs. This work presents a total of over 300 practical circuits, diagrams, and tables.Chapter 1 outlines the basic principles and the different types of generator. Chapters 2 to 9 deal with a specific type of waveform generator, including sine, square, triangular, sawtooth, and special waveform generators pulse. These chapters also include pulse gen

  2. Security electronics circuits manual

    CERN Document Server

    MARSTON, R M

    1998-01-01

    Security Electronics Circuits Manual is an invaluable guide for engineers and technicians in the security industry. It will also prove to be a useful guide for students and experimenters, as well as providing experienced amateurs and DIY enthusiasts with numerous ideas to protect their homes, businesses and properties.As with all Ray Marston's Circuits Manuals, the style is easy-to-read and non-mathematical, with the emphasis firmly on practical applications, circuits and design ideas. The ICs and other devices used in the practical circuits are modestly priced and readily available ty

  3. Printed circuit board industry.

    Science.gov (United States)

    LaDou, Joseph

    2006-05-01

    The printed circuit board is the platform upon which microelectronic components such as semiconductor chips and capacitors are mounted. It provides the electrical interconnections between components and is found in virtually all electronics products. Once considered low technology, the printed circuit board is evolving into a high-technology product. Printed circuit board manufacturing is highly complicated, requiring large equipment investments and over 50 process steps. Many of the high-speed, miniaturized printed circuit boards are now manufactured in cleanrooms with the same health and safety problems posed by other microelectronics manufacturing. Asia produces three-fourths of the world's printed circuit boards. In Asian countries, glycol ethers are the major solvents used in the printed circuit board industry. Large quantities of hazardous chemicals such as formaldehyde, dimethylformamide, and lead are used by the printed circuit board industry. For decades, chemically intensive and often sloppy manufacturing processes exposed tens of thousands of workers to a large number of chemicals that are now known to be reproductive toxicants and carcinogens. The printed circuit board industry has exposed workers to high doses of toxic metals, solvents, acids, and photolithographic chemicals. Only recently has there been any serious effort to diminish the quantity of lead distributed worldwide by the printed circuit board industry. Billions of electronics products have been discarded in every region of the world. This paper summarizes recent regulatory and enforcement efforts.

  4. Electronic circuit realization of the logistic map

    Indian Academy of Sciences (India)

    Madhekar Suneel

    2006-02-01

    An electronic circuit realization of the logistic difference equation is presented using analog electronics. The behaviour of the realized system is evaluated against computer simulations of the same. The circuit is found to exhibit the entire range of dynamics of the logistic equation: fixed points, periodicity, period doubling, chaos and intermittency. Quantitative measurements of the dynamics of the realized system are presented and are found to be in good agreement with the theoretical values. Some possible applications of such a realization are briefly discussed.

  5. Mouse Social Network Dynamics and Community Structure are Associated with Plasticity-Related Brain Gene Expression.

    Science.gov (United States)

    Williamson, Cait M; Franks, Becca; Curley, James P

    2016-01-01

    Laboratory studies of social behavior have typically focused on dyadic interactions occurring within a limited spatiotemporal context. However, this strategy prevents analyses of the dynamics of group social behavior and constrains identification of the biological pathways mediating individual differences in behavior. In the current study, we aimed to identify the spatiotemporal dynamics and hierarchical organization of a large social network of male mice. We also sought to determine if standard assays of social and exploratory behavior are predictive of social behavior in this social network and whether individual network position was associated with the mRNA expression of two plasticity-related genes, DNA methyltransferase 1 and 3a. Mice were observed to form a hierarchically organized social network and self-organized into two separate social network communities. Members of both communities exhibited distinct patterns of socio-spatial organization within the vivaria that was not limited to only agonistic interactions. We further established that exploratory and social behaviors in standard behavioral assays conducted prior to placing the mice into the large group was predictive of initial network position and behavior but were not associated with final social network position. Finally, we determined that social network position is associated with variation in mRNA levels of two neural plasticity genes, DNMT1 and DNMT3a, in the hippocampus but not the mPOA. This work demonstrates the importance of understanding the role of social context and complex social dynamics in determining the relationship between individual differences in social behavior and brain gene expression.

  6. From Structural Variation of Gene Molecules to Chromatin Dynamics and Transcriptional Bursting

    Directory of Open Access Journals (Sweden)

    Hinrich Boeger

    2015-06-01

    Full Text Available Transcriptional activation of eukaryotic genes is accompanied, in general, by a change in the sensitivity of promoter chromatin to endonucleases. The structural basis of this alteration has remained elusive for decades; but the change has been viewed as a transformation of one structure into another, from “closed” to “open” chromatin. In contradistinction to this static and deterministic view of the problem, a dynamical and probabilistic theory of promoter chromatin has emerged as its solution. This theory, which we review here, explains observed variation in promoter chromatin structure at the level of single gene molecules and provides a molecular basis for random bursting in transcription—the conjecture that promoters stochastically transition between transcriptionally conducive and inconducive states. The mechanism of transcriptional regulation may be understood only in probabilistic terms.

  7. Evolutionary dynamics and genetic diversity from three genes of Anguillid rhabdovirus

    DEFF Research Database (Denmark)

    Bellec, Laure; Cabon, Joelle; Bergmann, Sven

    2014-01-01

    Wild freshwater eel populations have dramatically declined in recent past decades in Europe and America, partially through the impact of several factors including the wide spread of infectious diseases. The anguillid rhabdoviruses eel virus European X (EVEX) and eel virus American (EVA) potentially...... play a role in this decline, even if their real contribution is still unclear. In this study, we investigate the evolutionary dynamics and genetic diversity of anguiillid rhabdoviruses by analysing sequences from the glycoprotein, nucleoprotein and phosphoprotein (P) genes of 57 viral strains collected...... from seven countries over 40 years using maximum-likelihood and Bayesian approaches. Phylogenetic trees from the three genes are congruent and allow two monophyletic groups, European and American, to be clearly distinguished. Results of nucleotide substitution rates per site per year indicate...

  8. Regulatory circuit for responses of nitrogen catabolic gene expression to the GLN3 and DAL80 proteins and nitrogen catabolite repression in Saccharomyces cerevisiae.

    Science.gov (United States)

    Daugherty, J R; Rai, R; el Berry, H M; Cooper, T G

    1993-01-01

    We demonstrate that expression of the UGA1, CAN1, GAP1, PUT1, PUT2, PUT4, and DAL4 genes is sensitive to nitrogen catabolite repression. The expression of all these genes, with the exception of UGA1 and PUT2, also required a functional GLN3 protein. In addition, GLN3 protein was required for expression of the DAL1, DAL2, DAL7, GDH1, and GDH2 genes. The UGA1, CAN1, GAP1, and DAL4 genes markedly increased their expression when the DAL80 locus, encoding a negative regulatory element, was disrupted. Expression of the GDH1, PUT1, PUT2, and PUT4 genes also responded to DAL80 disruption, but much more modestly. Expression of GLN1 and GDH2 exhibited parallel responses to the provision of asparagine and glutamine as nitrogen sources but did not follow the regulatory responses noted above for the nitrogen catabolic genes such as DAL5. Steady-state mRNA levels of both genes did not significantly decrease when glutamine was provided as nitrogen source but were lowered by the provision of asparagine. They also did not respond to disruption of DAL80.

  9. A state space representation of VAR models with sparse learning for dynamic gene networks.

    Science.gov (United States)

    Kojima, Kaname; Yamaguchi, Rui; Imoto, Seiya; Yamauchi, Mai; Nagasaki, Masao; Yoshida, Ryo; Shimamura, Teppei; Ueno, Kazuko; Higuchi, Tomoyuki; Gotoh, Noriko; Miyano, Satoru

    2010-01-01

    We propose a state space representation of vector autoregressive model and its sparse learning based on L1 regularization to achieve efficient estimation of dynamic gene networks based on time course microarray data. The proposed method can overcome drawbacks of the vector autoregressive model and state space model; the assumption of equal time interval and lack of separation ability of observation and systems noises in the former method and the assumption of modularity of network structure in the latter method. However, in a simple implementation the proposed model requires the calculation of large inverse matrices in a large number of times during parameter estimation process based on EM algorithm. This limits the applicability of the proposed method to a relatively small gene set. We thus introduce a new calculation technique for EM algorithm that does not require the calculation of inverse matrices. The proposed method is applied to time course microarray data of lung cells treated by stimulating EGF receptors and dosing an anticancer drug, Gefitinib. By comparing the estimated network with the control network estimated using non-treated lung cells, perturbed genes by the anticancer drug could be found, whose up- and down-stream genes in the estimated networks may be related to side effects of the anticancer drug.

  10. Gene Expression Dynamics Inspector (GEDI): for integrative analysis of expression profiles

    Science.gov (United States)

    Eichler, Gabriel S.; Huang, Sui; Ingber, Donald E.

    2003-01-01

    Genome-wide expression profiles contain global patterns that evade visual detection in current gene clustering analysis. Here, a Gene Expression Dynamics Inspector (GEDI) is described that uses self-organizing maps to translate high-dimensional expression profiles of time courses or sample classes into animated, coherent and robust mosaics images. GEDI facilitates identification of interesting patterns of molecular activity simultaneously across gene, time and sample space without prior assumption of any structure in the data, and then permits the user to retrieve genes of interest. Important changes in genome-wide activities may be quickly identified based on 'Gestalt' recognition and hence, GEDI may be especially useful for non-specialist end users, such as physicians. AVAILABILITY: GEDI v1.0 is written in Matlab, and binary Matlab.dll files which require Matlab to run can be downloaded for free by academic institutions at http://www.chip.org/ge/gedihome.html Supplementary information: http://www.chip.org/ge/gedihome.html.

  11. Dynamic regulation of glutamic acid decarboxylase 65 gene expression in rat testis

    Institute of Scientific and Technical Information of China (English)

    Haixiong Liu; Shifeng Li; Yunbin Zhang; Yuanchang Yan; Yiping Li

    2009-01-01

    Glutamate decarboxylase 65 (GAD65) produces γ-amino-butyric acid,the main inhibitory neurotransmitter in adult mammalian brain.Previous experiments,per-formed in brain,showed that GAD65 gene possesses two TATA-less promoters,although the significance is unknown.Here,by rapid amplification of cDNA ends method,two distinct GAD65 mRNA isoforms transcribed from two independent clusters of transcription start sites were identified in post-natal rat testis.RT-PCR results revealed that the two mRNA isoforms had distinct expression patterns during post-natal testis maturation,suggesting that GAD65 gene expression was regulated by alternative promoters at the transcription level.By using GAD65-speciflc antibodies,western blotting analysis showed that the 58-kDa GAD65,N-terminal 69 amino acids truncated form of full-length GAD65 protein,was developmentally expressed during post-natal testis matu-ration,suggesting that GAD65 gene expression in testis may also be regulated by post-translational processing.Confocal immunofluorescence microscopy revealed that GAD65 protein was presented in Leydig cells of Day 1 testis,primary spermatocytes and spermatids of post-natal of Day 90 testis.The above results suggested that GAD65 gene expression is dynamically regulated at mul-tiple levels during post-natal testis maturation.

  12. Dynamic expression of combinatorial replication-dependent histone variant genes during mouse spermatogenesis.

    Science.gov (United States)

    Sun, Rongfang; Qi, Huayu

    2014-01-01

    Nucleosomes are basic chromatin structural units that are formed by DNA sequences wrapping around histones. Global chromatin states in different cell types are specified by combinatorial effects of post-translational modifications of histones and the expression of histone variants. During mouse spermatogenesis, spermatogonial stem cells (SSCs) self-renew while undergo differentiation, events that occur in the company of constant re-modeling of chromatin structures. Previous studies have shown that testes contain highly expressed or specific histone variants to facilitate these epigenetic modifications. However, mechanisms of regulating the epigenetic changes and the specific histone compositions of spermatogenic cells are not fully understood. Using real time quantitative RT-PCR, we examined the dynamic expression of replication-dependent histone genes in post-natal mouse testes. It was found that distinct sets of histone genes are expressed in various spermatogenic cells at different stages during spermatogenesis. While gonocyte-enriched testes from mice at 2-dpp (days post partum) express pre-dominantly thirteen histone variant genes, SSC-stage testes at 9-dpp highly express a different set of eight histone genes. During differentiation stage when testes are occupied mostly by spermatocytes and spermatids, another twenty-two histone genes are expressed much higher than the rest, including previously known testis-specific hist1h1t, hist1h2ba and hist1h4c. In addition, histone genes that are pre-dominantly expressed in gonocytes and SSCs are also highly expressed in embryonic stem cells. Several of them were changed when embryoid bodies were formed from ES cells, suggesting their roles in regulating pluripotency of the cells. Further more, differentially expressed histone genes are specifically localized in either SSCs or spermatocytes and spermatids, as demonstrated by in situ hybridization using gene specific probes. Taken together, results presented here

  13. Logic circuits based on molecular spider systems.

    Science.gov (United States)

    Mo, Dandan; Lakin, Matthew R; Stefanovic, Darko

    2016-08-01

    Spatial locality brings the advantages of computation speed-up and sequence reuse to molecular computing. In particular, molecular walkers that undergo localized reactions are of interest for implementing logic computations at the nanoscale. We use molecular spider walkers to implement logic circuits. We develop an extended multi-spider model with a dynamic environment wherein signal transmission is triggered via localized reactions, and use this model to implement three basic gates (AND, OR, NOT) and a cascading mechanism. We develop an algorithm to automatically generate the layout of the circuit. We use a kinetic Monte Carlo algorithm to simulate circuit computations, and we analyze circuit complexity: our design scales linearly with formula size and has a logarithmic time complexity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Genetic circuit design automation.

    Science.gov (United States)

    Nielsen, Alec A K; Der, Bryan S; Shin, Jonghyeon; Vaidyanathan, Prashant; Paralanov, Vanya; Strychalski, Elizabeth A; Ross, David; Densmore, Douglas; Voigt, Christopher A

    2016-04-01

    Computation can be performed in living cells by DNA-encoded circuits that process sensory information and control biological functions. Their construction is time-intensive, requiring manual part assembly and balancing of regulator expression. We describe a design environment, Cello, in which a user writes Verilog code that is automatically transformed into a DNA sequence. Algorithms build a circuit diagram, assign and connect gates, and simulate performance. Reliable circuit design requires the insulation of gates from genetic context, so that they function identically when used in different circuits. We used Cello to design 60 circuits forEscherichia coli(880,000 base pairs of DNA), for which each DNA sequence was built as predicted by the software with no additional tuning. Of these, 45 circuits performed correctly in every output state (up to 10 regulators and 55 parts), and across all circuits 92% of the output states functioned as predicted. Design automation simplifies the incorporation of genetic circuits into biotechnology projects that require decision-making, control, sensing, or spatial organization.

  15. A Virtual Circuits Lab

    Science.gov (United States)

    Vick, Matthew E.

    2010-01-01

    The University of Colorado's Physics Education Technology (PhET) website offers free, high-quality simulations of many physics experiments that can be used in the classroom. The Circuit Construction Kit, for example, allows students to safely and constructively play with circuit components while learning the mathematics behind many circuit…

  16. A simple electronic circuit realization of the tent map

    Energy Technology Data Exchange (ETDEWEB)

    Campos-Canton, I. [Fac. de Ciencias, Universidad Autonoma de San Luis Potosi, Alvaro Obregon 64, 78000 San Luis Potosi, SLP (Mexico)], E-mail: icampos@galia.fc.uaslp.mx; Campos-Canton, E. [Departamento de Fisico Matematicas, Universidad Autonoma de San Luis Potosi, Alvaro Obregon 64, 78000 San Luis Potosi, SLP (Mexico)], E-mail: ecamp@uaslp.mx; Murguia, J.S. [Departamento de Fisico Matematicas, Universidad Autonoma de San Luis Potosi, Alvaro Obregon 64, 78000 San Luis Potosi, SLP (Mexico)], E-mail: ondeleto@uaslp.mx; Rosu, H.C. [Division de Materiales Avanzados, Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la presa San Jose 2055, 78216 San Luis Potosi, SLP (Mexico)], E-mail: hcr@ipicyt.edu.mx

    2009-10-15

    We present a very simple electronic implementation of the tent map, one of the best-known discrete dynamical systems. This is achieved by using integrated circuits and passive elements only. The experimental behavior of the tent map electronic circuit is compared with its numerical simulation counterpart. We find that the electronic circuit presents fixed points, periodicity, period doubling, chaos and intermittency that match with high accuracy the corresponding theoretical values.

  17. Static power dissipation in adder circuits: the UDSM domain

    Science.gov (United States)

    Cayouette, Steve; Al-Khalili, Dhamin

    2009-05-01

    This paper presents adder circuits of various architectures aimed at reducing static power dissipation. Circuit topologies for basic building blocks were evaluated for fabrication technologies of 65nm down to 32nm, and simulation results are presented. This work has lead to the development of various low power adder circuits and provides comparative analysis leading to the recommendation that a variable size block carry select adder is the best performer, taking into consideration both static and dynamic power dissipation.

  18. Quantum Memristors with Superconducting Circuits

    Science.gov (United States)

    Salmilehto, J.; Deppe, F.; di Ventra, M.; Sanz, M.; Solano, E.

    2017-02-01

    Memristors are resistive elements retaining information of their past dynamics. They have garnered substantial interest due to their potential for representing a paradigm change in electronics, information processing and unconventional computing. Given the advent of quantum technologies, a design for a quantum memristor with superconducting circuits may be envisaged. Along these lines, we introduce such a quantum device whose memristive behavior arises from quasiparticle-induced tunneling when supercurrents are cancelled. For realistic parameters, we find that the relevant hysteretic behavior may be observed using current state-of-the-art measurements of the phase-driven tunneling current. Finally, we develop suitable methods to quantify memory retention in the system.

  19. Quantum Memristors with Superconducting Circuits

    Science.gov (United States)

    Salmilehto, J.; Deppe, F.; Di Ventra, M.; Sanz, M.; Solano, E.

    2017-01-01

    Memristors are resistive elements retaining information of their past dynamics. They have garnered substantial interest due to their potential for representing a paradigm change in electronics, information processing and unconventional computing. Given the advent of quantum technologies, a design for a quantum memristor with superconducting circuits may be envisaged. Along these lines, we introduce such a quantum device whose memristive behavior arises from quasiparticle-induced tunneling when supercurrents are cancelled. For realistic parameters, we find that the relevant hysteretic behavior may be observed using current state-of-the-art measurements of the phase-driven tunneling current. Finally, we develop suitable methods to quantify memory retention in the system. PMID:28195193

  20. Dynamic QTL analysis and candidate gene mapping for waterlogging tolerance at maize seedling stage.

    Directory of Open Access Journals (Sweden)

    Khalid A Osman

    Full Text Available Soil waterlogging is one of the major abiotic stresses adversely affecting maize growth and yield. To identify dynamic expression of genes or quantitative trait loci (QTL, QTL associated with plant height, root length, root dry weight, shoot dry weight and total dry weight were identified via conditional analysis in a mixed linear model and inclusive composite interval mapping method at three respective periods under waterlogging and control conditions. A total of 13, 19 and 23 QTL were detected at stages 3D|0D (the period during 0-3 d of waterlogging, 6D|3D and 9D|6D, respectively. The effects of each QTL were moderate and distributed over nine chromosomes, singly explaining 4.14-18.88% of the phenotypic variation. Six QTL (ph6-1, rl1-2, sdw4-1, sdw7-1, tdw4-1 and tdw7-1 were identified at two consistent stages of seedling development, which could reflect a continuous expression of genes; the remaining QTL were detected at only one stage. Thus, expression of most QTL was influenced by the developmental status. In order to provide additional evidence regarding the role of corresponding genes in waterlogging tolerance, mapping of Expressed Sequence Tags markers and microRNAs were conducted. Seven candidate genes were observed to co-localize with the identified QTL on chromosomes 1, 4, 6, 7 and 9, and may be important candidate genes for waterlogging tolerance. These results are a good starting point for understanding the genetic basis for selectively expressing of QTL in different stress periods and the common genetic control mechanism of the co-localized traits.

  1. Evolutionary Dynamics of the Cellulose Synthase Gene Superfamily in Grasses1[OPEN

    Science.gov (United States)

    Schwerdt, Julian G.; Wright, Frank; Oehme, Daniel; Wagner, John M.; Shirley, Neil J.; Burton, Rachel A.; Schreiber, Miriam; Zimmer, Jochen; Marshall, David F.; Waugh, Robbie; Fincher, Geoffrey B.

    2015-01-01

    Phylogenetic analyses of cellulose synthase (CesA) and cellulose synthase-like (Csl) families from the cellulose synthase gene superfamily were used to reconstruct their evolutionary origins and selection histories. Counterintuitively, genes encoding primary cell wall CesAs have undergone extensive expansion and diversification following an ancestral duplication from a secondary cell wall-associated CesA. Selection pressure across entire CesA and Csl clades appears to be low, but this conceals considerable variation within individual clades. Genes in the CslF clade are of particular interest because some mediate the synthesis of (1,3;1,4)-β-glucan, a polysaccharide characteristic of the evolutionarily successful grasses that is not widely distributed elsewhere in the plant kingdom. The phylogeny suggests that duplication of either CslF6 and/or CslF7 produced the ancestor of a highly conserved cluster of CslF genes that remain located in syntenic regions of all the grass genomes examined. A CslF6-specific insert encoding approximately 55 amino acid residues has subsequently been incorporated into the gene, or possibly lost from other CslFs, and the CslF7 clade has undergone a significant long-term shift in selection pressure. Homology modeling and molecular dynamics of the CslF6 protein were used to define the three-dimensional dispositions of individual amino acids that are subject to strong ongoing selection, together with the position of the conserved 55-amino acid insert that is known to influence the amounts and fine structures of (1,3;1,4)-β-glucans synthesized. These wall polysaccharides are attracting renewed interest because of their central roles as sources of dietary fiber in human health and for the generation of renewable liquid biofuels. PMID:25999407

  2. Dynamic Epstein-Barr virus gene expression on the path to B-cell transformation.

    Science.gov (United States)

    Price, Alexander M; Luftig, Micah A

    2014-01-01

    Epstein-Barr virus (EBV) is an oncogenic human herpesvirus in the γ-herpesvirinae subfamily that contains a 170-180kb double-stranded DNA genome. In vivo, EBV commonly infects B and epithelial cells and persists for the life of the host in a latent state in the memory B-cell compartment of the peripheral blood. EBV can be reactivated from its latent state, leading to increased expression of lytic genes that primarily encode for enzymes necessary to replicate the viral genome and structural components of the virion. Lytic cycle proteins also aid in immune evasion, inhibition of apoptosis, and the modulation of other host responses to infection. In vitro, EBV has the potential to infect primary human B cells and induce cellular proliferation to yield effectively immortalized lymphoblastoid cell lines, or LCLs. EBV immortalization of B cells in vitro serves as a model system for studying EBV-mediated lymphomagenesis. While much is known about the steady-state viral gene expression within EBV-immortalized LCLs and other EBV-positive cell lines, relatively little is known about the early events after primary B-cell infection. It was previously thought that upon latent infection, EBV only expressed the well-characterized latency-associated transcripts found in LCLs. However, recent work has characterized the early, but transient, expression of lytic genes necessary for efficient transformation and delayed responses in the known latency genes. This chapter summarizes these recent findings that show how dynamic and controlled expression of multiple EBV genes can control the activation of B cells, entry into the cell cycle, the inhibition of apoptosis, and innate and adaptive immune responses.

  3. Assessing and selecting gene expression signals based upon the quality of the measured dynamics

    Directory of Open Access Journals (Sweden)

    Androulakis Ioannis P

    2009-02-01

    Full Text Available Abstract Background One of the challenges with modeling the temporal progression of biological signals is dealing with the effect of noise and the limited number of replicates at each time point. Given the rising interest in utilizing predictive mathematical models to describe the biological response of an organism or analysis such as clustering and gene ontology enrichment, it is important to determine whether the dynamic progression of the data has been accurately captured despite the limited number of replicates, such that one can have confidence that the results of the analysis are capturing important salient dynamic features. Results By pre-selecting genes based upon quality before the identification of differential expression via algorithm such as EDGE, it was found that the percentage of statistically enriched ontologies (p Conclusion We have developed an algorithm that quantifies the quality of temporal biological signal rather than whether the signal illustrates a significant change over the experimental time course. Because the use of these temporal signals, whether it is in mathematical modeling or clustering, focuses upon the entire time series, it is necessary to develop a method to quantify and select for signals which conform to this ideal. By doing this, we have demonstrated a marked and consistent improvement in the results of a clustering exercise over multiple experiments, microarray platforms, and experimental designs.

  4. Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo

    Science.gov (United States)

    Timme-Laragy, Alicia R.; Goldstone, Jared V.; Imhoff, Barry R.; Stegeman, John J.; Hahn, Mark E.; Hansen, Jason M.

    2013-01-01

    Embryonic development involves dramatic changes in cell proliferation and differentiation that must be highly coordinated and tightly regulated. Cellular redox balance is critical for cell fate decisions, but it is susceptible to disruption by endogenous and exogenous sources of oxidative stress. The most abundant endogenous non-protein antioxidant defense molecule is the tri-peptide glutathione (γ-glutamyl-cysteinylglycine, GSH), but the ontogeny of GSH concentration and redox state during early life stages is poorly understood. Here, we describe the GSH redox dynamics during embryonic and early larval development (0–5 days post-fertilization) in the zebrafish (Danio rerio), a model vertebrate embryo. We measured reduced and oxidized glutathione (GSH, GSSG) using HPLC, and calculated the whole embryo total glutathione (GSHT) concentrations and redox potentials (Eh) over 0–120 hours of zebrafish development (including mature oocytes, fertilization, mid-blastula transition, gastrulation, somitogenesis, pharyngula, pre-hatch embryos, and hatched eleutheroembryos). GSHT concentration doubled between 12 hours post fertilization (hpf) and hatching. The GSH Eh increased, becoming more oxidizing during the first 12 h, and then oscillated around −190 mV through organogenesis, followed by a rapid change, associated with hatching, to a more negative (more reducing) Eh (−220 mV). After hatching, Eh stabilized and remained steady through 120 hpf. The dynamic changes in GSH redox status and concentration defined discrete windows of development: primary organogenesis, organ differentiation, and larval growth. We identified the set of zebrafish genes involved in the synthesis, utilization, and recycling of GSH, including several novel paralogs, and measured how expression of these genes changes during development. Ontogenic changes in the expression of GSH-related genes support the hypothesis that GSH redox state is tightly regulated early in development. This study

  5. Cross-species gene-family fluctuations reveal the dynamics of horizontal transfers.

    Science.gov (United States)

    Grilli, Jacopo; Romano, Mariacristina; Bassetti, Federico; Cosentino Lagomarsino, Marco

    2014-06-01

    Prokaryotes vary their protein repertoire mainly through horizontal transfer and gene loss. To elucidate the links between these processes and the cross-species gene-family statistics, we perform a large-scale data analysis of the cross-species variability of gene-family abundance (the number of members of the family found on a given genome). We find that abundance fluctuations are related to the rate of horizontal transfers. This is rationalized by a minimal theoretical model, which predicts this link. The families that are not captured by the model show abundance profiles that are markedly peaked around a mean value, possibly because of specific abundance selection. Based on these results, we define an abundance variability index that captures a family's evolutionary behavior (and thus some of its relevant functional properties) purely based on its cross-species abundance fluctuations. Analysis and model, combined, show a quantitative link between cross-species family abundance statistics and horizontal transfer dynamics, which can be used to analyze genome 'flux'. Groups of families with different values of the abundance variability index correspond to genome sub-parts having different plasticity in terms of the level of horizontal exchange allowed by natural selection.

  6. Dynamic Regulation of the Adenosine Kinase Gene during Early Postnatal Brain Development and Maturation

    Science.gov (United States)

    Kiese, Katharina; Jablonski, Janos; Boison, Detlev; Kobow, Katja

    2016-01-01

    The ubiquitous metabolic intermediary and nucleoside adenosine is a “master regulator” in all living systems. Under baseline conditions adenosine kinase (ADK) is the primary enzyme for the metabolic clearance of adenosine. By regulating the availability of adenosine, ADK is a critical upstream regulator of complex homeostatic and metabolic networks. Not surprisingly, ADK dysfunction is involved in several pathologies, including diabetes, epilepsy, and cancer. ADK protein exists in the two isoforms nuclear ADK-L, and cytoplasmic ADK-S, which are subject to dynamic expression changes during brain development and in response to brain injury; however, gene expression changes of the Adk gene as well as regulatory mechanisms that direct the cell-type and isoform specific expression of ADK have never been investigated. Here we analyzed potential gene regulatory mechanisms that may influence Adk expression including DNA promoter methylation, histone modifications and transcription factor binding. Our data suggest binding of transcription factor SP1 to the Adk promoter influences the regulation of Adk expression. PMID:27812320

  7. Gene regulatory network modeling via global optimization of high-order dynamic Bayesian network

    Directory of Open Access Journals (Sweden)

    Xuan Nguyen

    2012-06-01

    Full Text Available Abstract Background Dynamic Bayesian network (DBN is among the mainstream approaches for modeling various biological networks, including the gene regulatory network (GRN. Most current methods for learning DBN employ either local search such as hill-climbing, or a meta stochastic global optimization framework such as genetic algorithm or simulated annealing, which are only able to locate sub-optimal solutions. Further, current DBN applications have essentially been limited to small sized networks. Results To overcome the above difficulties, we introduce here a deterministic global optimization based DBN approach for reverse engineering genetic networks from time course gene expression data. For such DBN models that consist only of inter time slice arcs, we show that there exists a polynomial time algorithm for learning the globally optimal network structure. The proposed approach, named GlobalMIT+, employs the recently proposed information theoretic scoring metric named mutual information test (MIT. GlobalMIT+ is able to learn high-order time delayed genetic interactions, which are common to most biological systems. Evaluation of the approach using both synthetic and real data sets, including a 733 cyanobacterial gene expression data set, shows significantly improved performance over other techniques. Conclusions Our studies demonstrate that deterministic global optimization approaches can infer large scale genetic networks.

  8. Approximate circuits for increased reliability

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Jason R.; Mayo, Jackson R.

    2015-08-18

    Embodiments of the invention describe a Boolean circuit having a voter circuit and a plurality of approximate circuits each based, at least in part, on a reference circuit. The approximate circuits are each to generate one or more output signals based on values of received input signals. The voter circuit is to receive the one or more output signals generated by each of the approximate circuits, and is to output one or more signals corresponding to a majority value of the received signals. At least some of the approximate circuits are to generate an output value different than the reference circuit for one or more input signal values; however, for each possible input signal value, the majority values of the one or more output signals generated by the approximate circuits and received by the voter circuit correspond to output signal result values of the reference circuit.

  9. Approximate circuits for increased reliability

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Jason R.; Mayo, Jackson R.

    2015-12-22

    Embodiments of the invention describe a Boolean circuit having a voter circuit and a plurality of approximate circuits each based, at least in part, on a reference circuit. The approximate circuits are each to generate one or more output signals based on values of received input signals. The voter circuit is to receive the one or more output signals generated by each of the approximate circuits, and is to output one or more signals corresponding to a majority value of the received signals. At least some of the approximate circuits are to generate an output value different than the reference circuit for one or more input signal values; however, for each possible input signal value, the majority values of the one or more output signals generated by the approximate circuits and received by the voter circuit correspond to output signal result values of the reference circuit.

  10. Fluctuation of Mesoscopic RLC Circuit at Finite Temperature

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-Yan; WANG Ji-Suo; FAN Hong-Yi

    2008-01-01

    We consider the fluctuation of mesoscopic RLC circuit at finite temperature since a resistance always produces Joule heat when the circuit is working. By virtue of the thermo field dynamics and the coherent thermo state representation we show that the quantum mechanical zero-point fluctuations of both charge and current increase with the rising temperature and the resistance value.

  11. Variable Time Base Integrator Circuit for Buffet Signal Measurements

    Science.gov (United States)

    Batts, Colossie N.

    1973-01-01

    A measurement circuit to obtain buffet data from wind tunnel models wherein a signal proportional to the average RMS value of buffet data is produced for subsequent recording. Feedback means are employed to suppress the D.C. portion of signals developed by the strain gages during dynamic testing. Automatic recording of gain settings of amplifiers employed in the circuit is also provided.

  12. Multi-qubit circuit quantum electrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Viehmann, Oliver

    2013-09-03

    Circuit QED systems are macroscopic, man-made quantum systems in which superconducting artificial atoms, also called Josephson qubits, interact with a quantized electromagnetic field. These systems have been devised to mimic the physics of elementary quantum optical systems with real atoms in a scalable and more flexible framework. This opens up a variety of possible applications of circuit QED systems. For instance, they provide a promising platform for processing quantum information. Recent years have seen rapid experimental progress on these systems, and experiments with multi-component circuit QED architectures are currently starting to come within reach. In this thesis, circuit QED systems with multiple Josephson qubits are studied theoretically. We focus on simple and experimentally realistic extensions of the currently operated circuit QED setups and pursue investigations in two main directions. First, we consider the equilibrium behavior of circuit QED systems containing a large number of mutually noninteracting Josephson charge qubits. The currently accepted standard description of circuit QED predicts the possibility of superradiant phase transitions in such systems. However, a full microscopic treatment shows that a no-go theorem for superradiant phase transitions known from atomic physics applies to circuit QED systems as well. This reveals previously unknown limitations of the applicability of the standard theory of circuit QED to multi-qubit systems. Second, we explore the potential of circuit QED for quantum simulations of interacting quantum many-body systems. We propose and analyze a circuit QED architecture that implements the quantum Ising chain in a time-dependent transverse magnetic field. Our setup can be used to study quench dynamics, the propagation of localized excitations, and other non-equilibrium features in this paradigmatic model in the theory of non-equilibrium thermodynamics and quantumcritical phenomena. The setup is based on a

  13. Plasmonic Nanoguides and Circuits

    CERN Document Server

    Bozhevolnyi, Sergey

    2008-01-01

    Modern communication systems dealing with huge amounts of data at ever increasing speed try to utilize the best aspects of electronic and optical circuits. Electronic circuits are tiny but their operation speed is limited, whereas optical circuits are extremely fast but their sizes are limited by diffraction. Waveguide components utilizing surface plasmon (SP) modes were found to combine the huge optical bandwidth and compactness of electronics, and plasmonics thereby began to be considered as the next chip-scale technology. In this book, the authors concentrate on the SP waveguide configurati

  14. Optoelectronics circuits manual

    CERN Document Server

    Marston, R M

    2013-01-01

    Optoelectronics Circuits Manual covers the basic principles and characteristics of the best known types of optoelectronic devices, as well as the practical applications of many of these optoelectronic devices. The book describes LED display circuits and LED dot- and bar-graph circuits and discusses the applications of seven-segment displays, light-sensitive devices, optocouplers, and a variety of brightness control techniques. The text also tackles infrared light-beam alarms and multichannel remote control systems. The book provides practical user information and circuitry and illustrations.

  15. Circuit analysis with Multisim

    CERN Document Server

    Baez-Lopez, David

    2011-01-01

    This book is concerned with circuit simulation using National Instruments Multisim. It focuses on the use and comprehension of the working techniques for electrical and electronic circuit simulation. The first chapters are devoted to basic circuit analysis.It starts by describing in detail how to perform a DC analysis using only resistors and independent and controlled sources. Then, it introduces capacitors and inductors to make a transient analysis. In the case of transient analysis, it is possible to have an initial condition either in the capacitor voltage or in the inductor current, or bo

  16. Modern TTL circuits manual

    CERN Document Server

    Marston, R M

    2013-01-01

    Modern TTL Circuits Manual provides an introduction to the basic principles of Transistor-Transistor Logic (TTL). This book outlines the major features of the 74 series of integrated circuits (ICs) and introduces the various sub-groups of the TTL family.Organized into seven chapters, this book begins with an overview of the basics of digital ICs. This text then examines the symbology and mathematics of digital logic. Other chapters consider a variety of topics, including waveform generator circuitry, clocked flip-flop and counter circuits, special counter/dividers, registers, data latches, com

  17. Pragmatic circuits frequency domain

    CERN Document Server

    Eccles, William

    2006-01-01

    Pragmatic Circuits: Frequency Domain goes through the Laplace transform to get from the time domain to topics that include the s-plane, Bode diagrams, and the sinusoidal steady state. This second of three volumes ends with a-c power, which, although it is just a special case of the sinusoidal steady state, is an important topic with unique techniques and terminology. Pragmatic Circuits: Frequency Domain is focused on the frequency domain. In other words, time will no longer be the independent variable in our analysis. The two other volumes in the Pragmatic Circuits series include titles on DC

  18. Troubleshooting analog circuits

    CERN Document Server

    Pease, Robert A

    1991-01-01

    Troubleshooting Analog Circuits is a guidebook for solving product or process related problems in analog circuits. The book also provides advice in selecting equipment, preventing problems, and general tips. The coverage of the book includes the philosophy of troubleshooting; the modes of failure of various components; and preventive measures. The text also deals with the active components of analog circuits, including diodes and rectifiers, optically coupled devices, solar cells, and batteries. The book will be of great use to both students and practitioners of electronics engineering. Other

  19. Monolithic microwave integrated circuits

    Science.gov (United States)

    Pucel, R. A.

    Monolithic microwave integrated circuits (MMICs), a new microwave technology which is expected to exert a profound influence on microwave circuit designs for future military systems as well as for the commercial and consumer markets, is discussed. The book contains an historical discussion followed by a comprehensive review presenting the current status in the field. The general topics of the volume are: design considerations, materials and processing considerations, monolithic circuit applications, and CAD, measurement, and packaging techniques. All phases of MMIC technology are covered, from design to testing.

  20. In vitro evaluation of herpes simplex virus type 1 thymidine kinase reporter system in dynamic studies of transcriptional gene regulation

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, C.-H. [Department of Medical Radiation Technology and Institute of Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Liu, R.-S. [Department of Medical Radiation Technology and Institute of Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); National Yang-Ming University Medical School and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei 112, Taiwan (China); Wang, H.-E. [Department of Medical Radiation Technology and Institute of Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Hwang, J.-J. [Department of Medical Radiation Technology and Institute of Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Deng, W.-P. [Institute of Biomedical Material, Taipei Medical University, Taipei 112, Taiwan (China); Chen, J.-C. [Department of Medical Radiation Technology and Institute of Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Chen, F.-D. [Department of Medical Radiation Technology and Institute of Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China) and Institute of Radiological Sciences, Central Taiwan University of Science and Technology Taichung 112, Taiwan (China)]. E-mail: d49220009@ym.edu.tw

    2006-07-15

    The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially regulated gene expression model in vitro. The dynamic transcriptional events mediating a series of doxycycline (Dox) inductions were monitored by HSV1-TK or by the firefly luciferase reporter gene using HSV1-TK enzyme activity assay and luciferase assay, respectively. The results of dynamic gene expression studies showed that the luciferase gene is an optimal reporter gene for monitoring short-timescale, dynamic transcriptional events mediating a series of Dox inductions, whereas the HSV1-tk is not optimal to achieve this purpose. Furthermore, the enzyme half-life of HSV1-TK in NG4TL4 cells is about 35 h after cycloheximide-induced protein inhibition. On the other hand, the results of an efflux assay of [{sup 131}I] FIAU and [{sup 3}H] GCV revealed that the molecular probe phosphorylated by HSV1-TK can be trapped long term within HSV1-TK stably transformed cells. Therefore, a long half-life radionuclide is not suitable for dynamic gene expression studies. Based on these results, we suggest that the HSV1-TK reporter system is not optimal for monitoring short-timescale dynamic processes such as kinetic gene expression controlled by

  1. RNAi dynamics in Juvenile Fasciola spp. Liver flukes reveals the persistence of gene silencing in vitro.

    Directory of Open Access Journals (Sweden)

    Paul McVeigh

    2014-09-01

    Full Text Available Fasciola spp. liver fluke cause pernicious disease in humans and animals. Whilst current control is unsustainable due to anthelmintic resistance, gene silencing (RNA interference, RNAi has the potential to contribute to functional validation of new therapeutic targets. The susceptibility of juvenile Fasciola hepatica to double stranded (dsRNA-induced RNAi has been reported. To exploit this we probe RNAi dynamics, penetrance and persistence with the aim of building a robust platform for reverse genetics in liver fluke. We describe development of standardised RNAi protocols for a commercially-available liver fluke strain (the US Pacific North West Wild Strain, validated via robust transcriptional silencing of seven virulence genes, with in-depth experimental optimisation of three: cathepsin L (FheCatL and B (FheCatB cysteine proteases, and a σ-class glutathione transferase (FheσGST.Robust transcriptional silencing of targets in both F. hepatica and Fasciola gigantica juveniles is achievable following exposure to long (200-320 nt dsRNAs or 27 nt short interfering (siRNAs. Although juveniles are highly RNAi-susceptible, they display slower transcript and protein knockdown dynamics than those reported previously. Knockdown was detectable following as little as 4h exposure to trigger (target-dependent and in all cases silencing persisted for ≥25 days following long dsRNA exposure. Combinatorial silencing of three targets by mixing multiple long dsRNAs was similarly efficient. Despite profound transcriptional suppression, we found a significant time-lag before the occurrence of protein suppression; FheσGST and FheCatL protein suppression were only detectable after 9 and 21 days, respectively.In spite of marked variation in knockdown dynamics, we find that a transient exposure to long dsRNA or siRNA triggers robust RNAi penetrance and persistence in liver fluke NEJs supporting the development of multiple-throughput phenotypic screens for control

  2. Hysteresis in a quantized superfluid 'atomtronic' circuit.

    Science.gov (United States)

    Eckel, Stephen; Lee, Jeffrey G; Jendrzejewski, Fred; Murray, Noel; Clark, Charles W; Lobb, Christopher J; Phillips, William D; Edwards, Mark; Campbell, Gretchen K

    2014-02-13

    Atomtronics is an emerging interdisciplinary field that seeks to develop new functional methods by creating devices and circuits where ultracold atoms, often superfluids, have a role analogous to that of electrons in electronics. Hysteresis is widely used in electronic circuits-it is routinely observed in superconducting circuits and is essential in radio-frequency superconducting quantum interference devices. Furthermore, it is as fundamental to superfluidity (and superconductivity) as quantized persistent currents, critical velocity and Josephson effects. Nevertheless, despite multiple theoretical predictions, hysteresis has not been previously observed in any superfluid, atomic-gas Bose-Einstein condensate. Here we directly detect hysteresis between quantized circulation states in an atomtronic circuit formed from a ring of superfluid Bose-Einstein condensate obstructed by a rotating weak link (a region of low atomic density). This contrasts with previous experiments on superfluid liquid helium where hysteresis was observed directly in systems in which the quantization of flow could not be observed, and indirectly in systems that showed quantized flow. Our techniques allow us to tune the size of the hysteresis loop and to consider the fundamental excitations that accompany hysteresis. The results suggest that the relevant excitations involved in hysteresis are vortices, and indicate that dissipation has an important role in the dynamics. Controlled hysteresis in atomtronic circuits may prove to be a crucial feature for the development of practical devices, just as it has in electronic circuits such as memories, digital noise filters (for example Schmitt triggers) and magnetometers (for example superconducting quantum interference devices).

  3. Dynamics of gene expression during development and expansion of vegetative stem internodes of bioenergy sorghum.

    Science.gov (United States)

    Kebrom, Tesfamichael H; McKinley, Brian; Mullet, John E

    2017-01-01

    developmental progression of vegetative stem internodes from initiation through full elongation in the sorghum genotype R.07020. Transcriptome profiling indicates that dynamic variation in the levels and action of GA, CK, IAA, BR, ethylene, ABA, and JA modulate gene expression and growth during internode growth and development. This study provides detailed microscopic and transcriptomic data useful for identifying genes and molecular pathways regulating internode elongation in response to various developmental and environmental signals.

  4. A novel approach for multi-domain and multi-gene family identification provides insights into evolutionary dynamics of disease resistance genes in core eudicot plants.

    Science.gov (United States)

    Hofberger, Johannes A; Zhou, Beifei; Tang, Haibao; Jones, Jonathan D G; Schranz, M Eric

    2014-11-08

    Recent advances in DNA sequencing techniques resulted in more than forty sequenced plant genomes representing a diverse set of taxa of agricultural, energy, medicinal and ecological importance. However, gene family curation is often only inferred from DNA sequence homology and lacks insights into evolutionary processes contributing to gene family dynamics. In a comparative genomics framework, we integrated multiple lines of evidence provided by gene synteny, sequence homology and protein-based Hidden Markov Modelling to extract homologous super-clusters composed of multi-domain resistance (R)-proteins of the NB-LRR type (for NUCLEOTIDE BINDING/LEUCINE-RICH REPEATS), that are involved in plant innate immunity. To assess the diversity of R-proteins within and between species, we screened twelve eudicot plant genomes including six major crops and found a total of 2,363 NB-LRR genes. Our curated R-proteins set shows a 50% average for tandem duplicates and a 22% fraction of gene copies retained from ancient polyploidy events (ohnologs). We provide evidence for strong positive selection and show significant differences in molecular evolution rates (Ka/Ks-ratio) among tandem- (mean = 1.59), ohnolog (mean = 1.36) and singleton (mean = 1.22) R-gene duplicates. To foster the process of gene-edited plant breeding, we report species-specific presence/absence of all 140 NB-LRR genes present in the model plant Arabidopsis and describe four distinct clusters of NB-LRR "gatekeeper" loci sharing syntenic orthologs across all analyzed genomes. By curating a near-complete set of multi-domain R-protein clusters in an eudicot-wide scale, our analysis offers significant insight into evolutionary dynamics underlying diversification of the plant innate immune system. Furthermore, our methods provide a blueprint for future efforts to identify and more rapidly clone functional NB-LRR genes from any plant species.

  5. Printed circuit for ATLAS

    CERN Multimedia

    Laurent Guiraud

    1999-01-01

    A printed circuit board made by scientists in the ATLAS collaboration for the transition radiaton tracker (TRT). This will read data produced when a high energy particle crosses the boundary between two materials with different electrical properties.

  6. Latching overcurrent circuit breaker

    Science.gov (United States)

    Moore, M. L.

    1970-01-01

    Circuit breaker consists of a preset current amplitude sensor, and a lamp-photo-resistor combination in a feedback arrangement which energizes a power switching relay. The ac input power is removed from the load at predetermined current amplitudes.

  7. High temperature circuit breaker

    Science.gov (United States)

    Edwards, R. N.; Travis, E. F.

    1970-01-01

    Alternating current circuit breaker is suitable for reliable long-term service at 1000 deg F in the vacuum conditions of outer space. Construction materials are resistant to nuclear radiation and vacuum welding. Service test conditions and results are given.

  8. Overriding Faulty Circuit Breakers

    Science.gov (United States)

    Robbins, Richard L.; Pierson, Thomas E.

    1987-01-01

    Retainer keeps power on in emergency. Simple mechanical device attaches to failed aircraft-type push/pull circuit breaker to restore electrical power temporarily until breaker replaced. Device holds push/pull button in closed position; unnecessary for crewmember to hold button in position by continual finger pressure. Sleeve and plug hold button in, overriding mechanical failure in circuit breaker. Windows in sleeve show button position.

  9. Do genes and environment meet to regulate cerebrospinal fluid dynamics? Relevance for schizophrenia.

    Directory of Open Access Journals (Sweden)

    Joana A Palha

    2012-08-01

    Full Text Available Schizophrenia is a neurodevelopment disorder in which the interplay of genes and environment contributes to disease onset and establishment. The most consistent pathological feature in schizophrenic patients is an enlargement of the brain ventricles. Yet, so far, no study has related this finding with dysfunction of the choroid plexus, the epithelial cell monolayer located within the brain ventricles that is responsible for the production of most of the cerebrospinal fluid (CSF. Enlarged brain ventricles are already present at the time of disease onset (young adulthood and, of notice, isolated mild ventriculomegaly detected in utero is associated with subsequent mild neurodevelopmental abnormalities similar to those observed in children at high risk of developing schizophrenia. Here we propose that an altered choroid plexus/CSF dynamics during neurodevelopment may be considered as a risk, causative and/or participating-key factor for development of schizophrenia.

  10. Heterogeneous photonic integrated circuits

    Science.gov (United States)

    Fang, Alexander W.; Fish, Gregory; Hall, Eric

    2012-01-01

    Photonic Integrated Circuits (PICs) have been dichotomized into circuits with high passive content (silica and silicon PLCs) and high active content (InP tunable lasers and transceivers) due to the trade-off in material characteristics used within these two classes. This has led to restrictions in the adoption of PICs to systems in which only one of the two classes of circuits are required to be made on a singular chip. Much work has been done to create convergence in these two classes by either engineering the materials to achieve the functionality of both device types on a single platform, or in epitaxial growth techniques to transfer one material to the next, but have yet to demonstrate performance equal to that of components fabricated in their native substrates. Advances in waferbonding techniques have led to a new class of heterogeneously integrated photonic circuits that allow for the concurrent use of active and passive materials within a photonic circuit, realizing components on a transferred substrate that have equivalent performance as their native substrate. In this talk, we review and compare advances made in heterogeneous integration along with demonstrations of components and circuits enabled by this technology.

  11. Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis

    Science.gov (United States)

    Shen, Keyue; Luk, Samantha; Elman, Jessica; Murray, Ryan; Mukundan, Shilpaa; Parekkadan, Biju

    2016-02-01

    Cancer-associated fibroblasts (CAFs) are a major cancer-promoting component in the tumor microenvironment (TME). The dynamic role of human CAFs in cancer progression has been ill-defined because human CAFs lack a unique marker needed for a cell-specific, promoter-driven knockout model. Here, we developed an engineered human CAF cell line with an inducible suicide gene to enable selective in vivo elimination of human CAFs at different stages of xenograft tumor development, effectively circumventing the challenge of targeting a cell-specific marker. Suicide-engineered CAFs were highly sensitive to apoptosis induction in vitro and in vivo by the addition of a simple small molecule inducer. Selection of timepoints for targeted CAF apoptosis in vivo during the progression of a human breast cancer xenograft model was guided by a bi-phasic host cytokine response that peaked at early timepoints after tumor implantation. Remarkably, we observed that the selective apoptosis of CAFs at these early timepoints did not affect primary tumor growth, but instead increased the presence of tumor-associated macrophages and the metastatic spread of breast cancer cells to the lung and bone. The study revealed a dynamic relationship between CAFs and cancer metastasis that has counter-intuitive ramifications for CAF-targeted therapy.

  12. Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism.

    Science.gov (United States)

    Mentch, Samantha J; Mehrmohamadi, Mahya; Huang, Lei; Liu, Xiaojing; Gupta, Diwakar; Mattocks, Dwight; Gómez Padilla, Paola; Ables, Gene; Bamman, Marcas M; Thalacker-Mercer, Anna E; Nichenametla, Sailendra N; Locasale, Jason W

    2015-11-01

    S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) link one-carbon metabolism to methylation status. However, it is unknown whether regulation of SAM and SAH by nutrient availability can be directly sensed to alter the kinetics of key histone methylation marks. We provide evidence that the status of methionine metabolism is sufficient to determine levels of histone methylation by modulating SAM and SAH. This dynamic interaction led to rapid changes in H3K4me3, altered gene transcription, provided feedback regulation to one-carbon metabolism, and could be fully recovered upon restoration of methionine. Modulation of methionine in diet led to changes in metabolism and histone methylation in the liver. In humans, methionine variability in fasting serum was commensurate with concentrations needed for these dynamics and could be partly explained by diet. Together these findings demonstrate that flux through methionine metabolism and the sensing of methionine availability may allow direct communication to the chromatin state in cells.

  13. Compensatory Drift and the Evolutionary Dynamics of Dosage-Sensitive Duplicate Genes.

    Science.gov (United States)

    Thompson, Ammon; Zakon, Harold H; Kirkpatrick, Mark

    2016-02-01

    Dosage-balance selection preserves functionally redundant duplicates (paralogs) at the optimum for their combined expression. Here we present a model of the dynamics of duplicate genes coevolving under dosage-balance selection. We call this the compensatory drift model. Results show that even when strong dosage-balance selection constrains total expression to the optimum, expression of each duplicate can diverge by drift from its original level. The rate of divergence slows as the strength of stabilizing selection, the size of the mutation effect, and/or the size of the population increases. We show that dosage-balance selection impedes neofunctionalization early after duplication but can later facilitate it. We fit this model to data from sodium channel duplicates in 10 families of teleost fish; these include two convergent lineages of electric fish in which one of the duplicates neofunctionalized. Using the model, we estimated the strength of dosage-balance selection for these genes. The results indicate that functionally redundant paralogs still may undergo radical functional changes after a prolonged period of compensatory drift.

  14. A hybrid dynamic Bayesian network approach for modelling temporal associations of gene expressions for hypertension diagnosis.

    Science.gov (United States)

    Akutekwe, Arinze; Seker, Huseyin

    2014-01-01

    Computational and machine learning techniques have been applied in identifying biomarkers and constructing predictive models for diagnosis of hypertension. Strategies such as improved classification rules based on decision trees have been proposed. Other techniques such as Fuzzy Expert Systems (FES) and Neuro-Fuzzy Systems (NFS) have recently been applied. However, these methods lack the ability to detect temporal relationships among biomarker genes that will aid better understanding of the mechanism of hypertension disease. In this paper we apply a proposed two-stage bio-network construction approach that combines the power and computational efficiency of classification methods with the well-established predictive ability of Dynamic Bayesian Network. We demonstrate our method using the analysis of male young-onset hypertension microarray dataset. Four key genes were identified by the Least Angle Shrinkage and Selection Operator (LASSO) and three Support Vector Machine Recursive Feature Elimination (SVM-RFE) methods. Results show that cell regulation FOXQ1 may inhibit the expression of focusyltransferase-6 (FUT6) and that ABCG1 ATP-binding cassette sub-family G may also play inhibitory role against NR2E3 nuclear receptor sub-family 2 and CGB2 Chromatin Gonadotrophin.

  15. Modeling Deterministic Chaos Using Electronic Circuits

    Directory of Open Access Journals (Sweden)

    T. Gotthans

    2011-06-01

    Full Text Available This paper brings a note on systematic circuit synthesis methods for modeling the dynamical systems given by mathematical model. Both classical synthesis and integrator based method is demonstrated via the relatively complicated real physical systems with possible chaotic solution. A variety of the different active building blocks are utilized to make the final circuits as simple as possible while preserving easily measurable voltage-mode state variables. Brief experimental verification, i.e. oscilloscope screenshots, is presented. The observed attractors have some structural stability and good relationship to their numerically integrated counterparts.

  16. Estimating the short-circuit impedance

    DEFF Research Database (Denmark)

    Nielsen, Arne Hejde; Pedersen, Knud Ole Helgesen; Poulsen, Niels Kjølstad

    1997-01-01

    and current are derived each period, and the short-circuit impedance is estimated from variations in these components created by load changes in the grid. Due to the noisy and dynamic grid with high harmonic distortion it is necessary to threat the calculated values statistical. This is done recursively...... through a RLS-algorithm. The algorithms have been tested and implemented on a PC at a 132 kV substation supplying a rolling mill. Knowing the short-circuit impedance gives the rolling mill an opportunity to adjust the arc furnace operation to keep flicker below a certain level. Therefore, the PC performs...

  17. Programming a Pavlovian-like conditioning circuit in Escherichia coli

    Science.gov (United States)

    Zhang, Haoqian; Lin, Min; Shi, Handuo; Ji, Weiyue; Huang, Longwen; Zhang, Xiaomeng; Shen, Shan; Gao, Rencheng; Wu, Shuke; Tian, Chengzhe; Yang, Zhenglin; Zhang, Guosheng; He, Siheng; Wang, Hao; Saw, Tiffany; Chen, Yiwei; Ouyang, Qi

    2014-01-01

    Synthetic genetic circuits are programmed in living cells to perform predetermined cellular functions. However, designing higher-order genetic circuits for sophisticated cellular activities remains a substantial challenge. Here we program a genetic circuit that executes Pavlovian-like conditioning, an archetypical sequential-logic function, in Escherichia coli. The circuit design is first specified by the subfunctions that are necessary for the single simultaneous conditioning, and is further genetically implemented using four function modules. During this process, quantitative analysis is applied to the optimization of the modules and fine-tuning of the interconnections. Analogous to classical Pavlovian conditioning, the resultant circuit enables the cells to respond to a certain stimulus only after a conditioning process. We show that, although the conditioning is digital in single cells, a dynamically progressive conditioning process emerges at the population level. This circuit, together with its rational design strategy, is a key step towards the implementation of more sophisticated cellular computing.

  18. Integrated signaling pathway and gene expression regulatory model to dissect dynamics of Escherichia coli challenged mammary epithelial cells.

    Science.gov (United States)

    den Breems, Nicoline Y; Nguyen, Lan K; Kulasiri, Don

    2014-12-01

    Cells transform external stimuli, through the activation of signaling pathways, which in turn activate gene regulatory networks, in gene expression. As more omics data are generated from experiments, eliciting the integrated relationship between the external stimuli, the signaling process in the cell and the subsequent gene expression is a major challenge in systems biology. The complex system of non-linear dynamic protein interactions in signaling pathways and gene networks regulates gene expression. The complexity and non-linear aspects have resulted in the study of the signaling pathway or the gene network regulation in isolation. However, this limits the analysis of the interaction between the two components and the identification of the source of the mechanism differentiating the gene expression profiles. Here, we present a study of a model of the combined signaling pathway and gene network to highlight the importance of integrated modeling. Based on the experimental findings we developed a compartmental model and conducted several simulation experiments. The model simulates the mRNA expression of three different cytokines (RANTES, IL8 and TNFα) regulated by the transcription factor NFκB in mammary epithelial cells challenged with E. coli. The analysis of the gene network regulation identifies a lack of robustness and therefore sensitivity for the transcription factor regulation. However, analysis of the integrated signaling and gene network regulation model reveals distinctly different underlying mechanisms in the signaling pathway responsible for the variation between the three cytokine's mRNA expression levels. Our key findings reveal the importance of integrating the signaling pathway and gene expression dynamics in modeling. Modeling infers valid research questions which need to be verified experimentally and can assist in the design of future biological experiments.

  19. A dynamic multiarmed bandit-gene expression programming hyper-heuristic for combinatorial optimization problems.

    Science.gov (United States)

    Sabar, Nasser R; Ayob, Masri; Kendall, Graham; Qu, Rong

    2015-02-01

    Hyper-heuristics are search methodologies that aim to provide high-quality solutions across a wide variety of problem domains, rather than developing tailor-made methodologies for each problem instance/domain. A traditional hyper-heuristic framework has two levels, namely, the high level strategy (heuristic selection mechanism and the acceptance criterion) and low level heuristics (a set of problem specific heuristics). Due to the different landscape structures of different problem instances, the high level strategy plays an important role in the design of a hyper-heuristic framework. In this paper, we propose a new high level strategy for a hyper-heuristic framework. The proposed high-level strategy utilizes a dynamic multiarmed bandit-extreme value-based reward as an online heuristic selection mechanism to select the appropriate heuristic to be applied at each iteration. In addition, we propose a gene expression programming framework to automatically generate the acceptance criterion for each problem instance, instead of using human-designed criteria. Two well-known, and very different, combinatorial optimization problems, one static (exam timetabling) and one dynamic (dynamic vehicle routing) are used to demonstrate the generality of the proposed framework. Compared with state-of-the-art hyper-heuristics and other bespoke methods, empirical results demonstrate that the proposed framework is able to generalize well across both domains. We obtain competitive, if not better results, when compared to the best known results obtained from other methods that have been presented in the scientific literature. We also compare our approach against the recently released hyper-heuristic competition test suite. We again demonstrate the generality of our approach when we compare against other methods that have utilized the same six benchmark datasets from this test suite.

  20. Midbrain local circuits shape sound intensity codes.

    Science.gov (United States)

    Grimsley, Calum Alex; Sanchez, Jason Tait; Sivaramakrishnan, Shobhana

    2013-01-01

    Hierarchical processing of sensory information requires interaction at multiple levels along the peripheral to central pathway. Recent evidence suggests that interaction between driving and modulating components can shape both top down and bottom up processing of sensory information. Here we show that a component inherited from extrinsic sources combines with local components to code sound intensity. By applying high concentrations of divalent cations to neurons in the nucleus of the inferior colliculus in the auditory midbrain, we show that as sound intensity increases, the source of synaptic efficacy changes from inherited inputs to local circuits. In neurons with a wide dynamic range response to intensity, inherited inputs increase firing rates at low sound intensities but saturate at mid-to-high intensities. Local circuits activate at high sound intensities and widen dynamic range by continuously increasing their output gain with intensity. Inherited inputs are necessary and sufficient to evoke tuned responses, however local circuits change peak output. Push-pull driving inhibition and excitation create net excitatory drive to intensity-variant neurons and tune neurons to intensity. Our results reveal that dynamic range and tuning re-emerge in the auditory midbrain through local circuits that are themselves variable or tuned.

  1. Circuit simulation: some humbling thoughts

    Energy Technology Data Exchange (ETDEWEB)

    Wendt, Manfred; /Fermilab

    2006-01-01

    A short, very personal note on circuit simulation is presented. It does neither include theoretical background on circuit simulation, nor offers an overview of available software, but just gives some general remarks for a discussion on circuit simulator needs in context to the design and development of accelerator beam instrumentation circuits and systems.

  2. The elusive memristor: properties of basic electrical circuits

    Energy Technology Data Exchange (ETDEWEB)

    Joglekar, Yogesh N; Wolf, Stephen J [Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202 (United States)], E-mail: yojoglek@iupui.edu

    2009-07-15

    We present an introduction to and a tutorial on the properties of the recently discovered ideal circuit element, a memristor. By definition, a memristor M relates the charge q and the magnetic flux {phi} in a circuit and complements a resistor R, a capacitor C and an inductor L as an ingredient of ideal electrical circuits. The properties of these three elements and their circuits are a part of the standard curricula. The existence of the memristor as the fourth ideal circuit element was predicted in 1971 based on symmetry arguments, but was clearly experimentally demonstrated just last year. We present the properties of a single memristor, memristors in series and parallel, as well as ideal memristor-capacitor (MC), memristor-inductor (ML) and memristor-capacitor-inductor (MCL) circuits. We find that the memristor has hysteretic current-voltage characteristics. We show that the ideal MC (ML) circuit undergoes non-exponential charge (current) decay with two time scales and that by switching the polarity of the capacitor, an ideal MCL circuit can be tuned from overdamped to underdamped. We present simple models which show that these unusual properties are closely related to the memristor's internal dynamics. This tutorial complements the pedagogy of ideal circuit elements (R, C and L) and the properties of their circuits, and is aimed at undergraduate physics and electrical engineering students.

  3. Microwave RF antennas and circuits nonlinearity applications in engineering

    CERN Document Server

    Aluf, Ofer

    2017-01-01

    This book describes a new concept for analyzing RF/microwave circuits, which includes RF/microwave antennas. The book is unique in its emphasis on practical and innovative microwave RF engineering applications. The analysis is based on nonlinear dynamics and chaos models and shows comprehensive benefits and results. All conceptual RF microwave circuits and antennas are innovative and can be broadly implemented in engineering applications. Given the dynamics of RF microwave circuits and antennas, they are suitable for use in a broad range of applications. The book presents analytical methods for microwave RF antennas and circuit analysis, concrete examples, and geometric examples. The analysis is developed systematically, starting with basic differential equations and their bifurcations, and subsequently moving on to fixed point analysis, limit cycles and their bifurcations. Engineering applications include microwave RF circuits and antennas in a variety of topological structures, RFID ICs and antennas, micros...

  4. Synthesis of energy-efficient counters implemented in PLD circuits

    Science.gov (United States)

    Kulisz, Józef; Nawrot, Radosław; Kania, Dariusz

    2016-12-01

    The paper presents a comparison of four methods of implementing sequential circuits in Programmable Logic Devices in respect of dissipated power. Objective of the research was to investigate influence of different methods of "disabling" the clock signal on the dynamic power consumed by the circuit. The comparison is carried out using simple counter circuits, i. e. circuits the algorithm of which is described by linear graphs. However, the presented considerations are general, and can be applied to any sequential circuit. Results of simulation tests show that the method based on clock gating is the most efficient one, and it leads to significant reduction of the dissipated dynamic power. The authors also propose a simple modification of global clock network structures, to facilitate clock gating.

  5. On the Possibility of the Jerk Derivative in Electrical Circuits

    Directory of Open Access Journals (Sweden)

    J. F. Gómez-Aguilar

    2016-01-01

    Full Text Available A subclass of dynamical systems with a time rate of change of acceleration are called Newtonian jerky dynamics. Some mechanical and acoustic systems can be interpreted as jerky dynamics. In this paper we show that the jerk dynamics are naturally obtained for electrical circuits using the fractional calculus approach with order γ. We consider fractional LC and RL electrical circuits with 1⩽γ<2 for different source terms. The LC circuit has a frequency ω dependent on the order of the fractional differential equation γ, since it is defined as ω(γ=ω0γγ1-γ, where ω0 is the fundamental frequency. For γ=3/2, the system is described by a third-order differential equation with frequency ω~ω03/2, and assuming γ=2 the dynamics are described by a fourth differential equation for jerk dynamics with frequency ω~ω02.

  6. Low latency asynchronous interface circuits

    Energy Technology Data Exchange (ETDEWEB)

    Sadowski, Greg

    2017-06-20

    In one form, a logic circuit includes an asynchronous logic circuit, a synchronous logic circuit, and an interface circuit coupled between the asynchronous logic circuit and the synchronous logic circuit. The asynchronous logic circuit has a plurality of asynchronous outputs for providing a corresponding plurality of asynchronous signals. The synchronous logic circuit has a plurality of synchronous inputs corresponding to the plurality of asynchronous outputs, a stretch input for receiving a stretch signal, and a clock output for providing a clock signal. The synchronous logic circuit provides the clock signal as a periodic signal but prolongs a predetermined state of the clock signal while the stretch signal is active. The asynchronous interface detects whether metastability could occur when latching any of the plurality of the asynchronous outputs of the asynchronous logic circuit using said clock signal, and activates the stretch signal while the metastability could occur.

  7. Networks and their applications to biological systems: From ecological dynamics to gene regulation

    Science.gov (United States)

    Sevim, Volkan

    networks. The ability to evolve robust mutants is known to depend on the network architecture. We seek answers to the following questions. How do the dynamical properties and state-space structures of networks with high and low robustness differ? Does selection operate on the global dynamical behavior of the networks? What kind of state-space structures are favored by selection? First, we analytically show that the model random networks we use are intrinsically chaotic, i.e., they do not undergo an order-to-chaos phase transition with increasing connectivity, unlike their variants found in the literature. Then, we provide a damage propagation analysis and an extensive statistical analysis of state spaces of these model networks to show that the change in their dynamical properties due to stabilizing selection for optimal phenotypes is minor. Most notably, the networks that are most robust to both mutations and noise are highly chaotic. Certain properties of chaotic networks, such as being able to produce large attractor basins, can be useful for maintaining a stable gene-expression pattern. Our findings indicate that conventional measures of stability, such as the damage-propagation rate, do not provide much information about robustness to mutations or noise in model gene regulatory networks.

  8. A semiconductor laser excitation circuit

    Energy Technology Data Exchange (ETDEWEB)

    Kaadzunari, O.; Masaty, K.

    1984-03-27

    A semiconductor laser excitation circuit is patented that is designed for operation in a pulsed mode with a high pulse repetition frequency. This circuit includes, in addition to a semiconductor laser, a high speed photodetector, a reference voltage source, a comparator, and a pulse oscillator and modulator. If the circuit is built using standard silicon integrated circuits, its speed amounts to several hundred megahertz, if it is constructed using gallium arsenide integrated circuits, its speed is several gigahertz.

  9. Learning and evolution in bacterial taxis: an operational amplifier circuit modeling the computational dynamics of the prokaryotic 'two component system' protein network.

    Science.gov (United States)

    Di Paola, Vieri; Marijuán, Pedro C; Lahoz-Beltra, Rafael

    2004-01-01

    Adaptive behavior in unicellular organisms (i.e., bacteria) depends on highly organized networks of proteins governing purposefully the myriad of molecular processes occurring within the cellular system. For instance, bacteria are able to explore the environment within which they develop by utilizing the motility of their flagellar system as well as a sophisticated biochemical navigation system that samples the environmental conditions surrounding the cell, searching for nutrients or moving away from toxic substances or dangerous physical conditions. In this paper we discuss how proteins of the intervening signal transduction network could be modeled as artificial neurons, simulating the dynamical aspects of the bacterial taxis. The model is based on the assumption that, in some important aspects, proteins can be considered as processing elements or McCulloch-Pitts artificial neurons that transfer and process information from the bacterium's membrane surface to the flagellar motor. This simulation of bacterial taxis has been carried out on a hardware realization of a McCulloch-Pitts artificial neuron using an operational amplifier. Based on the behavior of the operational amplifier we produce a model of the interaction between CheY and FliM, elements of the prokaryotic two component system controlling chemotaxis, as well as a simulation of learning and evolution processes in bacterial taxis. On the one side, our simulation results indicate that, computationally, these protein 'switches' are similar to McCulloch-Pitts artificial neurons, suggesting a bridge between evolution and learning in dynamical systems at cellular and molecular levels and the evolutive hardware approach. On the other side, important protein 'tactilizing' properties are not tapped by the model, and this suggests further complexity steps to explore in the approach to biological molecular computing.

  10. Dynamics of the mammalian nucleus: can microscopic movements help us to understand our genes?

    Science.gov (United States)

    Sleeman, Judith E

    2004-12-15

    The cell is the basic building block of human life. Each of us has existed as a single cell--the fertilized egg--and each of us is made up of billions of cells specialized in many different ways to form our tissues and organs. The nucleus of the cell, described as far back as 1682, is known to be the site of storage of chromosomes that carry the essential and unique DNA blueprint for life. With the recent publication of the entire human genome, our knowledge of exactly what our genes say has increased immeasurably. This, however, is only a small part of the story. In order for the chromosomal genes to function correctly, a complex cellular machinery must rewrite (or transcribe) the genetic instructions of the DNA into a temporary messenger molecule, messenger RNA (mRNA), rearrange (or splice) this message into a readable format and then produce a protein that accurately represents the DNA code. It is these protein molecules that are the functional result of the genetic information. This whole process is termed 'gene expression'. Both transcription and splicing of the mRNA message are carried out in the nucleus. These events must be performed accurately and efficiently in a minute volume already full of highly packaged DNA. An ever-increasing number of sub-nuclear structures have been described, from the nucleolus (first described in 1835) to newly discovered 'paraspeckles' and 'clastosomes'. In fact, as increasing numbers of molecular probes become available, so the complexity of nuclear structure appears to expand. The functions of some of these structures are currently unknown. Those whose functions are, at least partly, understood play roles in gene expression. Interestingly, alterations in nuclear structure are associated with human diseases such as spinal muscular atrophy and promyelocytic leukaemia, suggesting that the control of nuclear organization may be vital to health. The dynamic nature of the structure of the mammalian nucleus has come under increasing

  11. Circuit for studying the spatial profile of a laser beam using a closed-circuit television camera

    Science.gov (United States)

    Navathe, C. P.; Narayan, B. S.; Oak, S. M.; Gupta, B. L.

    1988-11-01

    A circuit for studying the laser beam spatial intensity profile using a closed-circuit television camera (CCTV) has been developed. The camera gives an output proportional to the laser beam intensity in the form of a composite video signal. The circuit can select any scan line and the intensity variation along that line can be displayed on an oscilloscope. The circuit also generates a trigger pulse for firing the laser synchronized with the selected scan line. It can be operated in either a single-shot or repetitive mode. The circuit can be used for both pulsed and cw lasers. The dynamic range, resolution, linearity, and accuracy of measurement all depend on the CCTV camera and the oscilloscope used. The dynamic range and resolution for our particular vidicon is limited to 5 and 12 lp/mm (line pairs/mm), respectively, for a 15-ns excitation pulse and to 10 and 18 lp/mm for cw and long pulse signal.

  12. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  13. The Mind Grows Circuits

    CERN Document Server

    Panigrahy, Rina

    2012-01-01

    There is a vast supply of prior art that study models for mental processes. Some studies in psychology and philosophy approach it from an inner perspective in terms of experiences and percepts. Others such as neurobiology or connectionist-machines approach it externally by viewing the mind as complex circuit of neurons where each neuron is a primitive binary circuit. In this paper, we also model the mind as a place where a circuit grows, starting as a collection of primitive components at birth and then builds up incrementally in a bottom up fashion. A new node is formed by a simple composition of prior nodes when we undergo a repeated experience that can be described by that composition. Unlike neural networks, however, these circuits take "concepts" or "percepts" as inputs and outputs. Thus the growing circuits can be likened to a growing collection of lambda expressions that are built on top of one another in an attempt to compress the sensory input as a heuristic to bound its Kolmogorov Complexity.

  14. Use of the fluorescent timer DsRED-E5 as reporter to monitor dynamics of gene activity in plants

    NARCIS (Netherlands)

    Mirabella, R.; Franken, C.; Krogt, van der G.N.M.; Bisseling, T.; Geurts, R.

    2004-01-01

    Fluorescent proteins, such as green fluorescent protein and red fluorescent protein (DsRED), have become frequently used reporters in plant biology. However, their potential to monitor dynamic gene regulation is limited by their high stability. The recently made DsRED-E5 variant overcame this

  15. Use of the fluorescent timer DsRED-E5 as reporter to monitor dynamics of gene activity in plants

    NARCIS (Netherlands)

    Mirabella, R.; Franken, C.; Krogt, van der G.N.M.; Bisseling, T.; Geurts, R.

    2004-01-01

    Fluorescent proteins, such as green fluorescent protein and red fluorescent protein (DsRED), have become frequently used reporters in plant biology. However, their potential to monitor dynamic gene regulation is limited by their high stability. The recently made DsRED-E5 variant overcame this proble

  16. Multidisciplinary Modelling Tools for Power Electronic Circuits

    DEFF Research Database (Denmark)

    Bahman, Amir Sajjad

    This thesis presents multidisciplinary modelling techniques in a Design For Reliability (DFR) approach for power electronic circuits. With increasing penetration of renewable energy systems, the demand for reliable power conversion systems is becoming critical. Since a large part of electricity...... in reliability assessment of power modules, a three-dimensional lumped thermal network is proposed to be used for fast, accurate and detailed temperature estimation of power module in dynamic operation and different boundary conditions. Since an important issue in the reliability of power electronics...... are generic and valid to be used in circuit simulators or any programing software. These models are important building blocks for the reliable design process or performance assessment of power electronic circuits. The models can save time and cost in power electronics packaging and power converter to evaluate...

  17. The Armc10/SVH gene: genome context, regulation of mitochondrial dynamics and protection against Aβ-induced mitochondrial fragmentation

    Science.gov (United States)

    Serrat, R; Mirra, S; Figueiro-Silva, J; Navas-Pérez, E; Quevedo, M; López-Doménech, G; Podlesniy, P; Ulloa, F; Garcia-Fernàndez, J; Trullas, R; Soriano, E

    2014-01-01

    Mitochondrial function and dynamics are essential for neurotransmission, neural function and neuronal viability. Recently, we showed that the eutherian-specific Armcx gene cluster (Armcx1–6 genes), located in the X chromosome, encodes for a new family of proteins that localise to mitochondria, regulating mitochondrial trafficking. The Armcx gene cluster evolved by retrotransposition of the Armc10 gene mRNA, which is present in all vertebrates and is considered to be the ancestor gene. Here we investigate the genomic organisation, mitochondrial functions and putative neuroprotective role of the Armc10 ancestor gene. The genomic context of the Armc10 locus shows considerable syntenic conservation among vertebrates, and sequence comparisons and CHIP-data suggest the presence of at least three conserved enhancers. We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain. Furthermore, we show that Armc10 levels regulate mitochondrial trafficking in neurons, but not mitochondrial aggregation, by controlling the number of moving mitochondria. We further demonstrate that the Armc10 protein interacts with the KIF5/Miro1-2/Trak2 trafficking complex. Finally, we show that overexpression of Armc10 in neurons prevents Aβ-induced mitochondrial fission and neuronal death. Our data suggest both conserved and differential roles of the Armc10/Armcx gene family in regulating mitochondrial dynamics in neurons, and underscore a protective effect of the Armc10 gene against Aβ-induced toxicity. Overall, our findings support a further degree of regulation of mitochondrial dynamics in the brain of more evolved mammals. PMID:24722288

  18. Dynamics of current controlled switching converters under wide circuit parameter variation%电路参数宽范围变化时电流控制开关变换器的动力学研究

    Institute of Scientific and Technical Information of China (English)

    包伯成; 杨平; 马正华; 张希

    2012-01-01

    With current-controlled buck-boost converter used as an example, through a detailed description of the switch state of the switch- ing converter under wide circuit parameter variation, such as input voltage and load resistance variation, two inductor current borders in the current controlled switching converter are derived and an accurate discrete-time model is established. The validation of the discrete-time model is verified by a piecewise-linear model. Based on the discrete-time model, the complex dynamical behaviors ex- isting in switching converter, such as period-double bifurcation, border-collision bifurcation, robust chaos and intermittent chaos, etc., are revealed. By formulating the Jacobian, the maximum Lyapunov exponent and the movement trajectories of eigvalues with the vari- ations of circuit parameters are obtained. By utilizing the parameter-space maps, the operation-state regions corresponding to circuit parameter regions are estimated. Finally, an experimental setup is implemented, the corresponding observation results are consistent with those of theory analyses. In this paper the dynamics theory in switching converters is investigated systematically; the analysis methods and research results are helpful for designing and controlling switching converters.%以电流控制Buck—Boost变换器为例,通过对输入电压和负载电阻等电路参数宽范围变化时开关变换器的开关状态的完整描述,导出了电流控制开关变换器的两个电感电流边界,建立了它的精确离散时间模型,并利用分段线性模型验证了离散时间模型的正确性.基于离散时间模型,揭示了开关变换器存在周期分岔、边界碰撞分岔、鲁棒混沌和阵发混沌等复杂动力学行为;通过推演Jacobi矩阵,给出了电路参数变化时最大Lyapunov指数和特征值的运动轨迹;并采用参数空间映射图,由电路参数域对开关变换器的工作状态域进行了估计.最

  19. Beyond Optimality to Understanding Neuronal Circuits

    Science.gov (United States)

    Marder, Eve

    2010-03-01

    I will summarize recent theoretical and experimental work that shows that similar circuit outputs can be produced with highly variable circuit parameters. This work argues that the nervous system of each healthy individual has found a set of different solutions that give ``good enough'' circuit performance. I will use examples from theoretical and experimental studies using the crustacean stomatogastric nervous system to argue that synaptic and intrinsic currents can vary far more than the output of the circuit in which they are found. These data have significant implications for the mechanisms that maintain stable function over the animal's lifetime, and for the kinds of changes that allow the nervous system to recover function after injury. In this kind of complex system, merely collecting mean data from many individuals can lead to significant errors, and it becomes important to measure as many individual network parameters in each individual as possible. This work raises the question of the extent to which neuromodulation can be constant with underlying circuit parameter variation. To address this question, we construct two cell reciprocally inhibitory circuits using the dynamic clamp from biological GM neurons of the crab stomatogastric ganglion. We then describe the output of the circuits while sweeping through a range of synaptic and intrinsic conductances, first in control saline and then in the presence of serotonin. We find that serotonin extends the ranges of parameters that produce alternating bursting. Moreover, although serotonin's effects are highly robust and significant on the entire population, individual networks respond anomalously. These data demonstrate that while neuromodulation may have robust actions on a population, not all individuals may respond as do the majority. These findings have important implications for evolution.

  20. Dynamics of elimination of plasmids and expression of VEGF121 gene transfected into human mesenchymal stem cells by different methods.

    Science.gov (United States)

    Smirnikhina, S A; Lavrov, A V; Bochkov, N P

    2011-05-01

    We compared two methods of transfection (lipofection and electroporation) with plasmid containing VEGF121 gene in four cultures of mesenchymal stem cells from the human adipose tissue. The efficacy of transfection after 1 day, the dynamics of plasmid elimination after 3, 6, 9 days, and expression of the target gene were evaluated. Transfection by both methods failed in one of 4 cultures. Analysis of the plasmid elimination dynamics showed that the content of plasmids introduced by both methods decreased by 30-69% in all cultures by day 3 and then remained unchanged from day 3 to day 9. The expression of the target gene did not correlate with the content of plasmids in cells and varied by 2-10 times in control cells and cells transfected by both methods. Fluctuation of VEGF121 expression was not related to methylation.

  1. Sequence of a complete chicken BG haplotype shows dynamic expansion and contraction of two gene lineages with particular expression patterns.

    Directory of Open Access Journals (Sweden)

    Jan Salomonsen

    2014-06-01

    Full Text Available Many genes important in immunity are found as multigene families. The butyrophilin genes are members of the B7 family, playing diverse roles in co-regulation and perhaps in antigen presentation. In humans, a fixed number of butyrophilin genes are found in and around the major histocompatibility complex (MHC, and show striking association with particular autoimmune diseases. In chickens, BG genes encode homologues with somewhat different domain organisation. Only a few BG genes have been characterised, one involved in actin-myosin interaction in the intestinal brush border, and another implicated in resistance to viral diseases. We characterise all BG genes in B12 chickens, finding a multigene family organised as tandem repeats in the BG region outside the MHC, a single gene in the MHC (the BF-BL region, and another single gene on a different chromosome. There is a precise cell and tissue expression for each gene, but overall there are two kinds, those expressed by haemopoietic cells and those expressed in tissues (presumably non-haemopoietic cells, correlating with two different kinds of promoters and 5' untranslated regions (5'UTR. However, the multigene family in the BG region contains many hybrid genes, suggesting recombination and/or deletion as major evolutionary forces. We identify BG genes in the chicken whole genome shotgun sequence, as well as by comparison to other haplotypes by fibre fluorescence in situ hybridisation, confirming dynamic expansion and contraction within the BG region. Thus, the BG genes in chickens are undergoing much more rapid evolution compared to their homologues in mammals, for reasons yet to be understood.

  2. Revealing networks from dynamics: an introduction

    CERN Document Server

    Timme, Marc

    2014-01-01

    What can we learn from the collective dynamics of a complex network about its interaction topology? Taking the perspective from nonlinear dynamics, we briefly review recent progress on how to infer structural connectivity (direct interactions) from accessing the dynamics of the units. Potential applications range from interaction networks in physics, to chemical and metabolic reactions, protein and gene regulatory networks as well as neural circuits in biology and electric power grids or wireless sensor networks in engineering. Moreover, we briefly mention some standard ways of inferring effective or functional connectivity.

  3. Electronic circuits modeling using artificial neural networks

    Directory of Open Access Journals (Sweden)

    Andrejević Miona V.

    2003-01-01

    Full Text Available In this paper artificial neural networks (ANN are applied to modeling of electronic circuits. ANNs are used for application of the black-box modeling concept in the time domain. Modeling process is described, so the topology of the ANN, the testing signal used for excitation, together with the complexity of ANN are considered. The procedure is first exemplified in modeling of resistive circuits. MOS transistor, as a four-terminal device, is modeled. Then nonlinear negative resistive characteristic is modeled in order to be used as a piece-wise linear resistor in Chua's circuit. Examples of modeling nonlinear dynamic circuits are given encompassing a variety of modeling problems. A nonlinear circuit containing quartz oscillator is considered for modeling. Verification of the concept is performed by verifying the ability of the model to generalize i.e. to create acceptable responses to excitations not used during training. Implementation of these models within a behavioral simulator is exemplified. Every model is implemented in realistic surrounding in order to show its interaction, and of course, its usage and purpose.

  4. Primer printed circuit boards

    CERN Document Server

    Argyle, Andrew

    2009-01-01

    Step-by-step instructions for making your own PCBs at home. Making your own printed circuit board (PCB) might seem a daunting task, but once you master the steps, it's easy to attain professional-looking results. Printed circuit boards, which connect chips and other components, are what make almost all modern electronic devices possible. PCBs are made from sheets of fiberglass clad with copper, usually in multiplelayers. Cut a computer motherboard in two, for instance, and you'll often see five or more differently patterned layers. Making boards at home is relatively easy

  5. Current Conveyor Equivalent Circuits

    Directory of Open Access Journals (Sweden)

    Tejmal S. Rathore

    2012-02-01

    Full Text Available An equivalence between a class of (current conveyor CC II+ and CC II- circuits is established. CC IIequivalent circuit uses one extra element. However, under certain condition, the extra element can be eliminated. As an illustration of the application of this equivalence, minimal first and second order all-pass filters are derived. Incertain cases, it is possible to compensate the effect of the input resistor of CC at port X. At the end, an open problem of realizing an Nth order (N > 2 minimal all-pass filter is stated.

  6. Circuit design for reliability

    CERN Document Server

    Cao, Yu; Wirth, Gilson

    2015-01-01

    This book presents physical understanding, modeling and simulation, on-chip characterization, layout solutions, and design techniques that are effective to enhance the reliability of various circuit units.  The authors provide readers with techniques for state of the art and future technologies, ranging from technology modeling, fault detection and analysis, circuit hardening, and reliability management. Provides comprehensive review on various reliability mechanisms at sub-45nm nodes; Describes practical modeling and characterization techniques for reliability; Includes thorough presentation of robust design techniques for major VLSI design units; Promotes physical understanding with first-principle simulations.

  7. Inrush Current Control Circuit

    Science.gov (United States)

    Cole, Steven W. (Inventor)

    2002-01-01

    An inrush current control circuit having an input terminal connected to a DC power supply and an output terminal connected to a load capacitor limits the inrush current that charges up the load capacitor during power up of a system. When the DC power supply applies a DC voltage to the input terminal, the inrush current control circuit produces a voltage ramp at the load capacitor instead of an abrupt DC voltage. The voltage ramp results in a constant low level current to charge up the load capacitor, greatly reducing the current drain on the DC power supply.

  8. Electronic circuits fundamentals & applications

    CERN Document Server

    Tooley, Mike

    2015-01-01

    Electronics explained in one volume, using both theoretical and practical applications.New chapter on Raspberry PiCompanion website contains free electronic tools to aid learning for students and a question bank for lecturersPractical investigations and questions within each chapter help reinforce learning Mike Tooley provides all the information required to get to grips with the fundamentals of electronics, detailing the underpinning knowledge necessary to appreciate the operation of a wide range of electronic circuits, including amplifiers, logic circuits, power supplies and oscillators. The

  9. Differential patterns in the periodicity and dynamics of clock gene expression in mouse liver and stomach.

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Francavilla, Massimo; Pazienza, Valerio; Benegiamo, Giorgia; Piepoli, Ada; Vinciguerra, Manlio; Giuliani, Francesco; Yamamoto, Takuro; Takumi, Toru

    2012-12-01

    The rhythmic recurrence of biological processes is driven by the functioning of cellular circadian clocks, operated by a set of genes and proteins that generate self-sustaining transcriptional-translational feedback loops with a free-running period of about 24 h. In the gastrointestinal apparatus, the functioning of the biological clocks shows distinct patterns in the different organs. The aim of this study was to evaluate the time-related variation of clock gene expression in mouse liver and stomach, two components of the digestive system sharing vascular and autonomic supply, but performing completely different functions. The authors analyzed the periodicity by cosinor analysis and the dynamics of variation by computing the fractional variation to assess the rate of change in gene expression. Five-week-old male Balb/c mice were exposed to 2 wks of 12-h light/12-h dark cycles, then kept in complete darkness for 3 d as a continuation of the dark span of the last light-dark cycle. The authors evaluated the expression of Bmal1, Clock, Cry1, Cry2, Per1, Per2, Per3, Rev-erbα, Rev-erbβ, Npas2, Timeless, Dbp, Csnk1d, and Csnk1e by using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in mouse liver and stomach. A significant 24-h rhythmic component was found for 10 genes in the liver (Bmal1, Clock, Cry1, Per1, Per2, Per3, Rev-erbα, Rev-erbβ, Npas2, and Dbp), and for 9 genes in the stomach (Bmal1, Cry1, Per1, Per2, Per3, Rev-erbα, Rev-erbβ, Npas2, and Dbp). In particular, Clock showed marked rhythm differences between liver and stomach, putatively due to some compensation by Npas2. The acrophase of the original values of Bmal1, Per2, Per3, Rev-erbα, Rev-erbβ, Npas2, and Dbp expression was delayed in the stomach, and the average delay expressed as mean ± SD was 14.30 ± 7.94 degrees (57.20 ± 31.78 minutes). A statistically significant difference was found in the acrophases of Bmal1 (p = .015) and Npas2 (p

  10. Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics

    Science.gov (United States)

    Eckhoff, Philip A.; Wenger, Edward A.; Godfray, H. Charles J.; Burt, Austin

    2017-01-01

    The renewed effort to eliminate malaria and permanently remove its tremendous burden highlights questions of what combination of tools would be sufficient in various settings and what new tools need to be developed. Gene drive mosquitoes constitute a promising set of tools, with multiple different possible approaches including population replacement with introduced genes limiting malaria transmission, driving-Y chromosomes to collapse a mosquito population, and gene drive disrupting a fertility gene and thereby achieving population suppression or collapse. Each of these approaches has had recent success and advances under laboratory conditions, raising the urgency for understanding how each could be deployed in the real world and the potential impacts of each. New analyses are needed as existing models of gene drive primarily focus on nonseasonal or nonspatial dynamics. We use a mechanistic, spatially explicit, stochastic, individual-based mathematical model to simulate each gene drive approach in a variety of sub-Saharan African settings. Each approach exhibits a broad region of gene construct parameter space with successful elimination of malaria transmission due to the targeted vector species. The introduction of realistic seasonality in vector population dynamics facilitates gene drive success compared with nonseasonal analyses. Spatial simulations illustrate constraints on release timing, frequency, and spatial density in the most challenging settings for construct success. Within its parameter space for success, each gene drive approach provides a tool for malaria elimination unlike anything presently available. Provided potential barriers to success are surmounted, each achieves high efficacy at reducing transmission potential and lower delivery requirements in logistically challenged settings. PMID:28028208

  11. A Dynamic Gene Regulatory Network Model That Recovers the Cyclic Behavior of Arabidopsis thaliana Cell Cycle

    Science.gov (United States)

    Ortiz-Gutiérrez, Elizabeth; García-Cruz, Karla; Azpeitia, Eugenio; Castillo, Aaron; Sánchez, María de la Paz; Álvarez-Buylla, Elena R.

    2015-01-01

    Cell cycle control is fundamental in eukaryotic development. Several modeling efforts have been used to integrate the complex network of interacting molecular components involved in cell cycle dynamics. In this paper, we aimed at recovering the regulatory logic upstream of previously known components of cell cycle control, with the aim of understanding the mechanisms underlying the emergence of the cyclic behavior of such components. We focus on Arabidopsis thaliana, but given that many components of cell cycle regulation are conserved among eukaryotes, when experimental data for this system was not available, we considered experimental results from yeast and animal systems. We are proposing a Boolean gene regulatory network (GRN) that converges into only one robust limit cycle attractor that closely resembles the cyclic behavior of the key cell-cycle molecular components and other regulators considered here. We validate the model by comparing our in silico configurations with data from loss- and gain-of-function mutants, where the endocyclic behavior also was recovered. Additionally, we approximate a continuous model and recovered the temporal periodic expression profiles of the cell-cycle molecular components involved, thus suggesting that the single limit cycle attractor recovered with the Boolean model is not an artifact of its discrete and synchronous nature, but rather an emergent consequence of the inherent characteristics of the regulatory logic proposed here. This dynamical model, hence provides a novel theoretical framework to address cell cycle regulation in plants, and it can also be used to propose novel predictions regarding cell cycle regulation in other eukaryotes. PMID:26340681

  12. Solution structure of the octamer motif in immunoglobulin genes via restrained molecular dynamics calculations.

    Science.gov (United States)

    Weisz, K; Shafer, R H; Egan, W; James, T L

    1994-01-11

    The solution structure of the DNA decamer d(CATTTGCATC)-d(GATGCAAATG), comprising the octamer motif of immunoglobulin genes, is determined by restrained molecular dynamics (rMD) simulations. The restraint data set includes interproton distances and torsion angles for the deoxyribose sugar ring which were previously obtained by a complete relaxation matrix analysis of the two-dimensional nuclear Overhauser enhancement (2D NOE) intensities and by the quantitative simulation of cross-peaks in double-quantum-filtered correlated (2QF-COSY) spectra. The influence of torsion angles and the number of experimental distance restraints on the structural refinement has been systematically examined. Omitting part of the experimental NOE-derived distances results in reduced restraint violations and lower R factors but impairs structural convergence in the rMD refinement. Eight separate restrained molecular dynamics simulations were carried out for 20 ps each, starting from either energy-minimized A- or B-DNA. Mutual atomic root-mean-square (rms) differences among the refined structures are well below 1 A and comparable to the rms fluctuations of the atoms about their average position, indicating convergence to essentially identical structures. The average refined structure was subjected to an additional 100 ps of rMD simulations and analyzed in terms of average torsion angles and helical parameters. The B-type duplex exhibits clear sequence-dependent variations in its geometry with a narrow minor groove at the T3.A3 tract and a large positive roll at the subsequent TG.CA step. This is accompanied by a noticeable bend of the global helix axis into the major groove. There is also evidence of significant flexibility of the sugar-phosphate backbone with rapid interconversion among different conformers.

  13. Horizontal gene transfer dynamics and distribution of fitness effects during microbial in silico evolution

    Directory of Open Access Journals (Sweden)

    Mozhayskiy Vadim

    2012-06-01

    Full Text Available Abstract Background Horizontal gene transfer (HGT is a process that facilitates the transfer of genetic material between organisms that are not directly related, and thus can affect both the rate of evolution and emergence of traits. Recent phylogenetic studies reveal HGT events are likely ubiquitous in the Tree of Life. However, our knowledge of HGT's role in evolution and biological organization is very limited, mainly due to the lack of ancestral evolutionary signatures and the difficulty to observe complex evolutionary dynamics in a laboratory setting. Here, we utilize a multi-scale microbial evolution model to comprehensively study the effect of HGT on the evolution of complex traits and organization of gene regulatory networks. Results Large-scale simulations reveal a distinct signature of the Distribution of Fitness Effect (DFE for HGT events: during evolution, while mutation fitness effects become more negative and neutral, HGT events result in a balanced effect distribution. In either case, lethal events are significantly decreased during evolution (33.0% to 3.2%, a clear indication of mutational robustness. Interestingly, evolution was accelerated when populations were exposed to correlated environments of increasing complexity, especially in the presence of HGT, a phenomenon that warrants further investigation. High HGT rates were found to be disruptive, while the average transferred fragment size was linked to functional module size in the underlying biological network. Network analysis reveals that HGT results in larger regulatory networks, but with the same sparsity level as those evolved in its absence. Observed phenotypic variability and co-existing solutions were traced to individual gain/loss of function events, while subsequent re-wiring after fragment integration was necessary for complex traits to emerge.

  14. Dynamics of gene expression patterns during early development of the European seabass (Dicentrarchus labrax).

    Science.gov (United States)

    Kaitetzidou, E; Xiang, J; Antonopoulou, E; Tsigenopoulos, C S; Sarropoulou, E

    2015-05-01

    Larval and embryonic stages are the most critical period in the life cycle of marine fish. Key developmental events occur early in development and are influenced by external parameters like stress, temperature, salinity, and photoperiodism. Any failure may cause malformations, developmental delays, poor growth, and massive mortalities. Advanced understanding of molecular processes underlying marine larval development may lead to superior larval rearing conditions. Today, the new sequencing and bioinformatic methods allow transcriptome screens comprising messenger (mRNA) and microRNA (miRNA) with the scope of detecting differential expression for any species of interest. In the present study, we applied Illumina technology to investigate the transcriptome of early developmental stages of the European seabass (Dicentrarchus labrax). The European seabass, in its natural environment, is a euryhaline species and has shown high adaptation processes in early life phases. During its embryonic and larval phases the European seabass lives in a marine environment and as a juvenile it migrates to coastal zones, estuaries, and lagoons. Investigating the dynamics of gene expression in its early development may shed light on factors promoting phenotypic plasticity and may also contribute to the improvement and advancement of rearing methods of the European seabass, a species of high economic importance in European and Mediterranean aquaculture. We present the identification, characterization, and expression of mRNA and miRNA, comprising paralogous genes and differentially spliced transcripts from early developmental stages of the European seabass. We further investigated the detection of possible interactions of miRNA with mRNA.

  15. Quantitative and functional dynamics of Dehalococcoides spp. and its tceA and vcrA genes under TCE exposure.

    Science.gov (United States)

    Doğan-Subaşi, Eylem; Bastiaens, Leen; Leys, Natalie; Boon, Nico; Dejonghe, Winnie

    2014-07-01

    This study aimed at monitoring the dynamics of phylogenetic and catabolic genes of a dechlorinating enrichment culture before, during, and after complete dechlorination of chlorinated compounds. More specifically, the effect of 40 μM trichloroethene (TCE) and 5.6 mM lactate on the gene abundance and activity of an enrichment culture was investigated for 40 days. Although tceA and vcrA gene copy numbers were relatively stable in DNA extracts over time, tceA and vcrA mRNA abundances were upregulated from undetectable levels to 2.96 × and 6.33 × 10⁴ transcripts/mL, respectively, only after exposure to TCE and lactate. While tceA gene transcripts decreased over time with TCE dechlorination, the vcrA gene was expressed steadily even when the concentration of vinyl chloride was at undetectable levels. In addition, ratios between catabolic and phylogenetic genes indicated that tceA and vcrA gene carrying organisms dechlorinated TCE and its produced daughter products, while vcrA gene was mainly responsible for the dechlorination of the lower VC concentrations in a later stage of degradation.

  16. Dynamics of gene duplication in the genomes of chlorophyll d-producing cyanobacteria: implications for the ecological niche.

    Science.gov (United States)

    Miller, Scott R; Wood, A Michelle; Blankenship, Robert E; Kim, Maria; Ferriera, Steven

    2011-01-01

    Gene duplication may be an important mechanism for the evolution of new functions and for the adaptive modulation of gene expression via dosage effects. Here, we analyzed the fate of gene duplicates for two strains of a novel group of cyanobacteria (genus Acaryochloris) that produces the far-red light absorbing chlorophyll d as its main photosynthetic pigment. The genomes of both strains contain an unusually high number of gene duplicates for bacteria. As has been observed for eukaryotic genomes, we find that the demography of gene duplicates can be well modeled by a birth-death process. Most duplicated Acaryochloris genes are of comparatively recent origin, are strain-specific, and tend to be located on different genetic elements. Analyses of selection on duplicates of different divergence classes suggest that a minority of paralogs exhibit near neutral evolutionary dynamics immediately following duplication but that most duplicate pairs (including those which have been retained for long periods) are under strong purifying selection against amino acid change. The likelihood of duplicate retention varied among gene functional classes, and the pronounced differences between strains in the pool of retained recent duplicates likely reflects differences in the nutrient status and other characteristics of their respective environments. We conclude that most duplicates are quickly purged from Acaryochloris genomes and that those which are retained likely make important contributions to organism ecology by conferring fitness benefits via gene dosage effects. The mechanism of enhanced duplication may involve homologous recombination between genetic elements mediated by paralogous copies of recA.

  17. Effects of coupling strength and space on the dynamics of coupled toggle switches in stochastic gene networks with multiple-delayed reactions

    Science.gov (United States)

    Ribeiro, Andre S.

    2007-06-01

    Genetic toggle switches (TSs) are one of the best studied small gene regulatory networks (GRNs), due to their simplicity and relevant role. They have been interpreted as decision circuits in cell differentiation, a process long hypothesized to be bistable [1], or as cellular memory units [2]. In these contexts, they must be reliable. Once a “decision” is made, the system must remain stable. One way to gain stability is by duplicating the genes of a TS and coupling the two TSs. Using a recent modeling strategy of GRNs, driven by a delayed stochastic simulation algorithm (delayed SSA) that allows modeling transcription and translation as multidelayed reactions, we analyze the stability of systems of coupled TSs. For this, we introduce the coupling strength (C) , a parameter to characterize the GRN structure, against which we compare the GRN stability (S) . We first show that time delays in transcription, associated to the promoter region release, ensure bistability of a TS, given no cooperative binding or self-activation reactions. Next, we couple two TSs and measure their toggling frequencies as C varies. Three dynamical regimes are observed: (i) for weak coupling, high frequency synchronized oscillations, (ii) for average coupling, low frequency synchronized oscillations, and (iii) for strong coupling the system becomes stable after a transient, in one of two steady states. The system stability, S , goes through a first order phase transition as C increases, in the average coupling regime. After, we study the effects of spatial separation in two compartments on the dynamics of two coupled TSs, where spatial separation is modeled as normally distributed random time delayed reactions. The phase transition of S , as C increases, occurs for lower values of C than when the two TSs are in the same compartment. Finally, we couple weakly and homogeneously several TSs within a single compartment and observe that as the number of coupled TSs increases, the system goes

  18. A Test Pattern Selection Method of Dynamic Burn-In for Logic Circuits%逻辑电路动态老化试验的输入矢量选择方法

    Institute of Scientific and Technical Information of China (English)

    崔小乐; 杨轩; 程作霖; 李崇仁

    2015-01-01

    针对逻辑电路动态老化试验的输入矢量优化问题,提出一种用于实现被测芯片的自加热能力的输入矢量优化选择方法。该方法采用转换故障模型,利用 ATPG 手段生成备选的输入矢量集合;为提高功耗权重计算的精确性,对不同类型的门电路在不同输入组合情况下的功耗权重进行了分析;根据逻辑仿真结果,引入功耗权重指标来描述在不同矢量组合输入条件下被测电路的功耗;以哈密尔顿回路为模型,采用遗传算法在功耗权重的引导下进行优化输入矢量序列的选取。在ISCAS’85基准电路上的实验数据表明,文中方法选取的输入矢量序列可在保持较高电路功耗的同时有效地减少电路中无跳变节点的数量,起到了功耗均匀化的效果。%Towards the requirement on input patterns of logic circuits for dynamic burn-in application, this paper proposes an input pattern selection method to self-heat the CUTs. The candidate input pattern set is generated by ATPG tools with transition fault model. The power weights of the different types of gate with various input combinations are investigated to lead to more accurate results. According to the result of logic simulation, a power weight is introduced to describe the power consumption of CUTs. Then the optimal pat-tern sequence is selected using a genetic algorithm directed by the power weight with a Hamilton Loop model. Experimental results on ISCAS’85 benchmark circuits show that, in comparison with the pattern pair to generate the maximum power dissipation, the pattern sequence generated can reduce the number of non-transition nodes while sustaining high burn-in power dissipation, which can make the power more uni-form in the CUTs.

  19. 远距离大动态范围电荷测量电路的设计%Design of long-distance and large-dynamic-range of charge measurement circuit

    Institute of Scientific and Technical Information of China (English)

    徐福珍; 杨红官; 常劲帆; 刘湘

    2016-01-01

    Background:The air shower core detector array (SCDA) is one of the important detectors to be constructed at the heart of the KM2A (one kilometer square extensive air shower array) with the area of 5000 m2, in large high altitude air shower observatory (LHAASO).Purpose:This study aims to design the readout electronics of SCDA for accurate charge measurement of the input photomultiplier tube (PMT) signal for three orders of magnitude. Methods:A 50-? impedance match between the "virtual" grounding and input end is employed to measure the charge by the charge integration method. The feasibility of impedance match is verified by "Pspice" simulation tool. The output current signal from the PMT is collected and processed by the readout electronics of charge integration circuitvia coaxial cable.Results:The performance testing in the laboratory shows that the designed circuit satisfies design requirements of the long-distance and large-dynamic-range charge measurement.Conclusion:The simulation and testing of "virtual" grounding impedance match validate the feasibility of this circuit. The readout electronics fulfills the application requirements of SCDA.%介绍了大型高海拔空气簇射观测站(Large High Altitude Air Shower Observatory,LHAASO)空气簇射芯探测器阵列(Shower core detector array,SCDA)读出电子学方案的预研设计.系统采用基于电荷积分法的电荷测量方案,读出电子学通过同轴电缆接收光电倍增管输出的电流信号;采用在输入端与电荷积分放大器的虚地点之间接入等效50?电阻的终端阻抗匹配方案,并通过Pspice仿真验证该阻抗匹配的可行性.电路测试结果表明,该电路能满足远距离10 bit大动态范围电荷测量的设计指标要求.

  20. ESD analog circuits and design

    CERN Document Server

    Voldman, Steven H

    2014-01-01

    A comprehensive and in-depth review of analog circuit layout, schematic architecture, device, power network and ESD design This book will provide a balanced overview of analog circuit design layout, analog circuit schematic development, architecture of chips, and ESD design.  It will start at an introductory level and will bring the reader right up to the state-of-the-art. Two critical design aspects for analog and power integrated circuits are combined. The first design aspect covers analog circuit design techniques to achieve the desired circuit performance. The second and main aspect pres

  1. Bioluminescent bioreporter integrated circuit

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, Michael L. (Knoxville, TN); Sayler, Gary S. (Blaine, TN); Paulus, Michael J. (Knoxville, TN)

    2000-01-01

    Disclosed are monolithic bioelectronic devices comprising a bioreporter and an OASIC. These bioluminescent bioreporter integrated circuit are useful in detecting substances such as pollutants, explosives, and heavy-metals residing in inhospitable areas such as groundwater, industrial process vessels, and battlefields. Also disclosed are methods and apparatus for environmental pollutant detection, oil exploration, drug discovery, industrial process control, and hazardous chemical monitoring.

  2. Superconducting Quantum Circuits

    NARCIS (Netherlands)

    Majer, J.B.

    2002-01-01

    This thesis describes a number of experiments with superconducting cir- cuits containing small Josephson junctions. The circuits are made out of aluminum islands which are interconnected with a very thin insulating alu- minum oxide layer. The connections form a Josephson junction. The current trough

  3. Quantum secure circuit evaluation

    Institute of Scientific and Technical Information of China (English)

    CHEN Huanhuan; LI Bin; ZHUANG Zhenquan

    2004-01-01

    In order to solve the problem of classical secure circuit evaluation, this paper proposes a quantum approach. In this approach, the method of inserting redundant entangled particles and quantum signature has been employed to strengthen the security of the system. Theoretical analysis shows that our solution is secure against classical and quantum attacks.

  4. Dynamic O-GlcNAc modification regulates CREB-mediated gene expression and memory formation.

    Science.gov (United States)

    Rexach, Jessica E; Clark, Peter M; Mason, Daniel E; Neve, Rachael L; Peters, Eric C; Hsieh-Wilson, Linda C

    2012-01-22

    The transcription factor cyclic AMP-response element binding protein (CREB) is a key regulator of many neuronal processes, including brain development, circadian rhythm and long-term memory. Studies of CREB have focused on its phosphorylation, although the diversity of CREB functions in the brain suggests additional forms of regulation. Here we expand on a chemoenzymatic strategy for quantifying glycosylation stoichiometries to characterize the functional roles of CREB glycosylation in neurons. We show that CREB is dynamically modified with an O-linked β-N-acetyl-D-glucosamine sugar in response to neuronal activity and that glycosylation represses CREB-dependent transcription by impairing its association with CREB-regulated transcription coactivator (CRTC; also known as transducer of regulated CREB activity). Blocking glycosylation of CREB alters cellular function and behavioral plasticity, enhancing both axonal and dendritic growth and long-term memory consolidation. Our findings demonstrate a new role for O-glycosylation in memory formation and provide a mechanistic understanding of how glycosylation contributes to critical neuronal functions. Moreover, we identify a previously unknown mechanism for the regulation of activity-dependent gene expression, neural development and memory.

  5. Microprocessor dynamics and interactions at endogenous imprinted C19MC microRNA genes.

    Science.gov (United States)

    Bellemer, Clément; Bortolin-Cavaillé, Marie-Line; Schmidt, Ute; Jensen, Stig Mølgaard Rask; Kjems, Jørgen; Bertrand, Edouard; Cavaillé, Jérôme

    2012-06-01

    Nuclear primary microRNA (pri-miRNA) processing catalyzed by the DGCR8-Drosha (Microprocessor) complex is highly regulated. Little is known, however, about how microRNA biogenesis is spatially organized within the mammalian nucleus. Here, we image for the first time, in living cells and at the level of a single microRNA cluster, the intranuclear distribution of untagged, endogenously-expressed pri-miRNAs generated at the human imprinted chromosome 19 microRNA cluster (C19MC), from the environment of transcription sites to single molecules of fully released DGCR8-bound pri-miRNAs dispersed throughout the nucleoplasm. We report that a large fraction of Microprocessor concentrates onto unspliced C19MC pri-miRNA deposited in close proximity to their genes. Our live-cell imaging studies provide direct visual evidence that DGCR8 and Drosha are targeted post-transcriptionally to C19MC pri-miRNAs as a preformed complex but dissociate separately. These dynamics support the view that, upon pri-miRNA loading and most probably concomitantly with Drosha-mediated cleavages, Microprocessor undergoes conformational changes that trigger the release of Drosha while DGCR8 remains stably bound to pri-miRNA.

  6. Top-level dynamics and the regulated gene response of feed-forward loop transcriptional motifs

    Science.gov (United States)

    Mayo, Michael; Abdelzaher, Ahmed; Perkins, Edward J.; Ghosh, Preetam

    2014-09-01

    Feed-forward loops are hierarchical three-node transcriptional subnetworks, wherein a top-level protein regulates the activity of a target gene via two paths: a direct-regulatory path, and an indirect route, whereby the top-level proteins act implicitly through an intermediate transcription factor. Using a transcriptional network of the model bacterium Escherichia coli, we confirmed that nearly all types of feed-forward loop were significantly overrepresented in the bacterial network. We then used mathematical modeling to study their dynamics by manipulating the rise times of the top-level protein concentration, termed the induction time, through alteration of the protein destruction rates. Rise times of the regulated proteins exhibited two qualitatively different regimes, depending on whether top-level inductions were "fast" or "slow." In the fast regime, rise times were nearly independent of rapid top-level inductions, indicative of biological robustness, and occurred when RNA production rate-limits the protein yield. Alternatively, the protein rise times were dependent upon slower top-level inductions, greater than approximately one bacterial cell cycle. An equation is given for this crossover, which depends upon three parameters of the direct-regulatory path: transcriptional cooperation at the DNA-binding site, a protein-DNA dissociation constant, and the relative magnitude of the top-level protien concentration.

  7. Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF ) after acute psychosocial stress.

    Science.gov (United States)

    Unternaehrer, E; Luers, P; Mill, J; Dempster, E; Meyer, A H; Staehli, S; Lieb, R; Hellhammer, D H; Meinlschmidt, G

    2012-08-14

    Environmentally induced epigenetic alterations are related to mental health. We investigated quantitative DNA methylation status before and after an acute psychosocial stressor in two stress-related genes: oxytocin receptor (OXTR) and brain-derived neurotrophic factor (BDNF ). The cross sectional study took place at the Division of Theoretical and Clinical Psychobiology, University of Trier, Germany and was conducted from February to August 2009. We included 83 participants aged 61-67 years. Thereof, 76 participants completed the full study procedure consisting of blood sampling before (pre-stress), 10 min after (post-stress) and 90 min after (follow-up) the Trier social stress test. We assessed quantitative DNA methylation of whole-blood cells using Sequenom EpiTYPER. Methylation status differed between sampling times in one target sequence of OXTR (POXTR (P=0.034), where it lost statistical significance when blood cell count was statistically controlled. We did not detect any time-associated differences in methylation status of the examined BDNF region. The results suggest a dynamic regulation of DNA methylation in OXTR-which may in part reflect changes in blood cell composition-but not BDNF after acute psychosocial stress. This may enhance the understanding of how psychosocial events alter DNA methylation and could provide new insights into the etiology of mental disorders.

  8. Hidden Markov induced Dynamic Bayesian Network for recovering time evolving gene regulatory networks

    Science.gov (United States)

    Zhu, Shijia; Wang, Yadong

    2015-12-01

    Dynamic Bayesian Networks (DBN) have been widely used to recover gene regulatory relationships from time-series data in computational systems biology. Its standard assumption is ‘stationarity’, and therefore, several research efforts have been recently proposed to relax this restriction. However, those methods suffer from three challenges: long running time, low accuracy and reliance on parameter settings. To address these problems, we propose a novel non-stationary DBN model by extending each hidden node of Hidden Markov Model into a DBN (called HMDBN), which properly handles the underlying time-evolving networks. Correspondingly, an improved structural EM algorithm is proposed to learn the HMDBN. It dramatically reduces searching space, thereby substantially improving computational efficiency. Additionally, we derived a novel generalized Bayesian Information Criterion under the non-stationary assumption (called BWBIC), which can help significantly improve the reconstruction accuracy and largely reduce over-fitting. Moreover, the re-estimation formulas for all parameters of our model are derived, enabling us to avoid reliance on parameter settings. Compared to the state-of-the-art methods, the experimental evaluation of our proposed method on both synthetic and real biological data demonstrates more stably high prediction accuracy and significantly improved computation efficiency, even with no prior knowledge and parameter settings.

  9. Hidden Markov induced Dynamic Bayesian Network for recovering time evolving gene regulatory networks.

    Science.gov (United States)

    Zhu, Shijia; Wang, Yadong

    2015-12-18

    Dynamic Bayesian Networks (DBN) have been widely used to recover gene regulatory relationships from time-series data in computational systems biology. Its standard assumption is 'stationarity', and therefore, several research efforts have been recently proposed to relax this restriction. However, those methods suffer from three challenges: long running time, low accuracy and reliance on parameter settings. To address these problems, we propose a novel non-stationary DBN model by extending each hidden node of Hidden Markov Model into a DBN (called HMDBN), which properly handles the underlying time-evolving networks. Correspondingly, an improved structural EM algorithm is proposed to learn the HMDBN. It dramatically reduces searching space, thereby substantially improving computational efficiency. Additionally, we derived a novel generalized Bayesian Information Criterion under the non-stationary assumption (called BWBIC), which can help significantly improve the reconstruction accuracy and largely reduce over-fitting. Moreover, the re-estimation formulas for all parameters of our model are derived, enabling us to avoid reliance on parameter settings. Compared to the state-of-the-art methods, the experimental evaluation of our proposed method on both synthetic and real biological data demonstrates more stably high prediction accuracy and significantly improved computation efficiency, even with no prior knowledge and parameter settings.

  10. Exogenous reference gene normalization for real-time reverse transcription-polymerase chain reaction analysis under dynamic endogenous transcription

    Institute of Scientific and Technical Information of China (English)

    Stephen Johnston; Zachary Gallaher; Krzysztof Czaja

    2012-01-01

    Quantitative real-time reverse transcription-polymerase chain reaction (qPCR) is widely used to investigate transcriptional changes following experimental manipulations to the nervous system. Despite the widespread utilization of qPCR, the interpretation of results is marred by the lack of a suitable reference gene due to the dynamic nature of endogenous transcription. To address this inherent deficiency, we investigated the use of an exogenous spike-in mRNA, luciferase, as an internal reference gene for the 2-ΔΔCt normalization method. To induce dynamic transcription, we systemically administered capsaicin, a neurotoxin selective for C-type sensory neurons expressing the TRPV-1 receptor, to adult male Sprague-Dawley rats. We later isolated nodose ganglia for qPCR analysis with the reference being either exogenous luciferase mRNA or the commonly used endogenous reference β-III tubulin. The exogenous luciferase mRNA reference clearly demonstrated the dynamic expression of the endogenous reference. Furthermore, variability of the endogenous reference would lead to misinterpretation of other genes of interest. In conclusion, traditional reference genes are often unstable under physiologically normal situations, and certainly unstable following the damage to the nervous system. The use of exogenous spike-in reference provides a consistent and easily implemented alternative for the analysis of qPCR data.

  11. Dynamics of immune system gene expression upon bacterial challenge and wounding in a social insect (Bombus terrestris).

    Science.gov (United States)

    Erler, Silvio; Popp, Mario; Lattorff, H Michael G

    2011-03-29

    The innate immune system which helps individuals to combat pathogens comprises a set of genes representing four immune system pathways (Toll, Imd, JNK and JAK/STAT). There is a lack of immune genes in social insects (e.g. honeybees) when compared to Diptera. Potentially, this might be compensated by an advanced system of social immunity (synergistic action of several individuals). The bumble bee, Bombus terrestris, is a primitively eusocial species with an annual life cycle and colonies headed by a single queen. We used this key pollinator to study the temporal dynamics of immune system gene expression in response to wounding and bacterial challenge.Antimicrobial peptides (AMP) (abaecin, defensin 1, hymenoptaecin) were strongly up-regulated by wounding and bacterial challenge, the latter showing a higher impact on the gene expression level. Sterile wounding down-regulated TEP A, an effector gene of the JAK/STAT pathway, and bacterial infection influenced genes of the Imd (relish) and JNK pathway (basket). Relish was up-regulated within the first hour after bacterial challenge, but decreased strongly afterwards. AMP expression following wounding and bacterial challenge correlates with the expression pattern of relish whereas correlated expression with dorsal was absent. Although expression of AMPs was high, continuous bacterial growth was observed throughout the experiment.Here we demonstrate for the first time the temporal dynamics of immune system gene expression in a social insect. Wounding and bacterial challenge affected the innate immune system significantly. Induction of AMP expression due to wounding might comprise a pre-adaptation to accompanying bacterial infections. Compared with solitary species this social insect exhibits reduced immune system efficiency, as bacterial growth could not be inhibited. A negative feedback loop regulating the Imd-pathway is suggested. AMPs, the end product of the Imd-pathway, inhibited the up-regulation of the transcription

  12. Dynamics of immune system gene expression upon bacterial challenge and wounding in a social insect (Bombus terrestris.

    Directory of Open Access Journals (Sweden)

    Silvio Erler

    Full Text Available The innate immune system which helps individuals to combat pathogens comprises a set of genes representing four immune system pathways (Toll, Imd, JNK and JAK/STAT. There is a lack of immune genes in social insects (e.g. honeybees when compared to Diptera. Potentially, this might be compensated by an advanced system of social immunity (synergistic action of several individuals. The bumble bee, Bombus terrestris, is a primitively eusocial species with an annual life cycle and colonies headed by a single queen. We used this key pollinator to study the temporal dynamics of immune system gene expression in response to wounding and bacterial challenge.Antimicrobial peptides (AMP (abaecin, defensin 1, hymenoptaecin were strongly up-regulated by wounding and bacterial challenge, the latter showing a higher impact on the gene expression level. Sterile wounding down-regulated TEP A, an effector gene of the JAK/STAT pathway, and bacterial infection influenced genes of the Imd (relish and JNK pathway (basket. Relish was up-regulated within the first hour after bacterial challenge, but decreased strongly afterwards. AMP expression following wounding and bacterial challenge correlates with the expression pattern of relish whereas correlated expression with dorsal was absent. Although expression of AMPs was high, continuous bacterial growth was observed throughout the experiment.Here we demonstrate for the first time the temporal dynamics of immune system gene expression in a social insect. Wounding and bacterial challenge affected the innate immune system significantly. Induction of AMP expression due to wounding might comprise a pre-adaptation to accompanying bacterial infections. Compared with solitary species this social insect exhibits reduced immune system efficiency, as bacterial growth could not be inhibited. A negative feedback loop regulating the Imd-pathway is suggested. AMPs, the end product of the Imd-pathway, inhibited the up-regulation of the

  13. Dynamic expression analysis of early response genes induced by potato virus Y in PVY-resistant Nicotiana tabacum.

    Science.gov (United States)

    Chen, Shuai; Li, Fengxia; Liu, Dan; Jiang, Caihong; Cui, Lijie; Shen, Lili; Liu, Guanshan; Yang, Aiguo

    2017-02-01

    Dynamic transcriptional changes of the host early responses genes were detected in PVY-resistant tobacco varieties infected with Potato virus Y; PVY resistance is a complex process that needs series of stress responses. Potato virus Y (PVY) causes a severe viral disease in cultivated crops, especially in Solanum plants. To understand the molecular basis of plant responses to the PVY stress, suppression subtractive hybridization (SSH) and microarray approaches were combined to identify the potentially important or novel genes that were involved in early stages (12 h, 1, 2, 3, 5, 8 days) of tobacco response to PVY infection. Dynamic changes of the host plant early responses to PVY infection on a transcriptional level were detected. In total, 167 different expressed ESTs were identified. The majority of genes involved in the metabolic process were found to be down-regulated at 12 h and 1 day, and then up-regulated at least one later period. Genes related to signaling and transcriptions were almost up-regulated at 12 h, 1 or 2 days, while stress response genes were almost up-regulated at a later stage. Genes involved in transcription, transport, cell wall, and several stress responses were found to have changed expression during the PVY infection stage, and numbers of these genes have not been previously reported to be associated with tobacco PVY infection. The diversity expression of these genes indicated that PVY resistance is a complex process that needs a series of stress responses. To resist the PVY infection, the tobacco plant has numerous active and silent responses.

  14. Resistor Combinations for Parallel Circuits.

    Science.gov (United States)

    McTernan, James P.

    1978-01-01

    To help simplify both teaching and learning of parallel circuits, a high school electricity/electronics teacher presents and illustrates the use of tables of values for parallel resistive circuits in which total resistances are whole numbers. (MF)

  15. Electronic circuits and systems: A compilation. [including integrated circuits, logic circuits, varactor diode circuits, low pass filters, and optical equipment circuits

    Science.gov (United States)

    1975-01-01

    Technological information is presented electronic circuits and systems which have potential utility outside the aerospace community. Topics discussed include circuit components such as filters, converters, and integrators, circuits designed for use with specific equipment or systems, and circuits designed primarily for use with optical equipment or displays.

  16. The LMT circuit and SPICE

    DEFF Research Database (Denmark)

    Lindberg, Erik; Murali, K.; Tamacevicius, Arunas

    2006-01-01

    The state equations of the LMT circuit are modeled as a dedicated analogue computer circuit and solved by means of PSpice. The nonlinear part of the system is studied. Problems with the PSpice program are presented.......The state equations of the LMT circuit are modeled as a dedicated analogue computer circuit and solved by means of PSpice. The nonlinear part of the system is studied. Problems with the PSpice program are presented....

  17. Behavioral synthesis of asynchronous circuits

    DEFF Research Database (Denmark)

    Nielsen, Sune Fallgaard

    2005-01-01

    This thesis presents a method for behavioral synthesis of asynchronous circuits, which aims at providing a synthesis flow which uses and tranfers methods from synchronous circuits to asynchronous circuits. We move the synchronous behavioral synthesis abstraction into the asynchronous handshake...... is idle. This reduces unnecessary switching activity in the individual functional units and therefore the energy consumption of the entire circuit. A collection of behavioral synthesis algorithms have been developed allowing the designer to perform time and power constrained design space exploration...

  18. Diode, transistor & fet circuits manual

    CERN Document Server

    Marston, R M

    2013-01-01

    Diode, Transistor and FET Circuits Manual is a handbook of circuits based on discrete semiconductor components such as diodes, transistors, and FETS. The book also includes diagrams and practical circuits. The book describes basic and special diode characteristics, heat wave-rectifier circuits, transformers, filter capacitors, and rectifier ratings. The text also presents practical applications of associated devices, for example, zeners, varicaps, photodiodes, or LEDs, as well as it describes bipolar transistor characteristics. The transistor can be used in three basic amplifier configuration

  19. State assignment approach to asynchronous CMOS circuit design

    Science.gov (United States)

    Kantabutra, Vitit; Andreou, Andreas G.

    1994-04-01

    We present a new algorithm for state assignment in asynchronous circuits so that for each circuit state transition, only one (secondary) state variable switches. No intermediate unstable states are used. The resultant circuits operate at optimum speed in terms of the number of transitions made and use only static CMOS gates. By reducing the number of switching events per state transition, noise due to the switching events is reduced and dynamic power dissipation may also be reduced. Our approach is suitable for asynchronous sequential circuits that are designed from flow tables or state transition diagrams. The proposed approach may also be useful for designing synchronous circuits, but explorations into the subject of clock power would be necessary to determine its usefulness.

  20. An Approach for Self-Timed Synchronous CMOS Circuit Design

    Science.gov (United States)

    Walker, Alvernon; Lala, Parag K.

    2001-01-01

    In this letter we present a timing and control strategy that can be used to realize synchronous systems with a level of performance that approaches that of asynchronous circuits or systems. This approach is based upon a single-phase synchronous circuit/system architecture with a variable period clock. The handshaking signals required for asynchronous self-timed circuits are not needed. Dynamic power supply current monitoring is used to generate the timing information, that is comparable to the completion signal found in self-timed circuits; this timing information is used to modi@ the circuit clock period. This letter is concluded with an example of the proposed approach applied to a static CMOS ripple-carry adder.