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Sample records for voltage feedback loop

  1. PI Closed-Loop Feedback Terminal Voltage Control Scheme based on Static VAR Compensator for Three-Phase Self-Excited Induction Generator

    NASA Astrophysics Data System (ADS)

    Ahmed, Tarek; Noro, Osamu; Nakaoka, Mutsuo

    In this paper, the practical impedance approach steady-state analysis in the frequency domain of the three-phase self-excited induction generator (SEIG) with a squirrel cage rotor is presented, along with its operating performance evaluations. The three-phase SEIG is driven by a variable-speed prime mover (VSPM) in addition to a constant-speed prime mover (CSPM) such as a wind turbine and a micro gas turbine for the clean alternative renewable energy in rural areas. The basic steady-state characteristics of the VSPM are considered in the three-phase SEIG approximate electro-mechanical equivalent circuit and the operating performances of the three-phase SEIG coupled by a VSPM and/or a CSPM in the steady-state analysis are evaluated and discussed on line under the conditions related to the speed changes of the prime mover and the electrical inductive load power variations with simple computation processing procedures. A three-phase SEIG prototype setup with a VSPM as well as a CSPM is implemented for the small-scale clean renewable and alternative energy utilizations. The experimental performance results give good agreements with those ones obtained from the simulation results. Furthermore, a PI controlled feedback closed-loop voltage regulation of the three-phase SEIG driven by the VSPM on the basis of the static VAR compensator (SVC) composed of the thyristor phase controlled reactor (TCR) in parallel with the thyristor switched capacitor (TSC) and the fixed excitation capacitor bank (FC) is designed and considered for the wind generation as a renewable power conditioner. The simulation analysis and experimental results obtained from the three-phase SEIG with the SVC for its voltage regulation prove the practical effectiveness of the additional SVC with the PI controller-based feedback loop in the steady-state operations in terms of the fast response and the high performances.

  2. Plasminogen Kringle 5 Induces Endothelial Cell Apoptosis by Triggering a Voltage-dependent Anion Channel 1 (VDAC1) Positive Feedback Loop*

    PubMed Central

    Li, Lei; Yao, Ya-Chao; Gu, Xiao-Qiong; Che, Di; Ma, Cai-Qi; Dai, Zhi-Yu; Li, Cen; Zhou, Ti; Cai, Wei-Bin; Yang, Zhong-Han; Yang, Xia; Gao, Guo-Quan

    2014-01-01

    Human plasminogen kringle 5 (K5) is known to display its potent anti-angiogenesis effect through inducing endothelial cell (EC) apoptosis, and the voltage-dependent anion channel 1 (VDAC1) has been identified as a receptor of K5. However, the exact role and underlying mechanisms of VDAC1 in K5-induced EC apoptosis remain elusive. In the current study, we showed that K5 increased the protein level of VDAC1, which initiated the mitochondrial apoptosis pathway of ECs. Our findings also showed that K5 inhibited the ubiquitin-dependent degradation of VDAC1 by promoting the phosphorylation of VDAC1, possibly at Ser-12 and Thr-107. The phosphorylated VDAC1 was attenuated by the AKT agonist, glycogen synthase kinase (GSK) 3β inhibitor, and siRNA, suggesting that K5 increased VDAC1 phosphorylation via the AKT-GSK3β pathway. Furthermore, K5 promoted cell surface translocation of VDAC1, and binding between K5 and VDAC1 was observed on the plasma membrane. HKI protein blocked the impact of K5 on the AKT-GSK3β pathway by competitively inhibiting the interaction of K5 and cell surface VDAC1. Moreover, K5-induced EC apoptosis was suppressed by VDAC1 antibody. These data show for the first time that K5-induced EC apoptosis is mediated by the positive feedback loop of “VDAC1-AKT-GSK3β-VDAC1,” which may provide new perspectives on the mechanisms of K5-induced apoptosis. PMID:25296756

  3. Monitoring Digital Closed-Loop Feedback Systems

    NASA Technical Reports Server (NTRS)

    Katz, Richard; Kleyner, Igor

    2011-01-01

    A technique of monitoring digital closed-loop feedback systems has been conceived. The basic idea is to obtain information on the performances of closed-loop feedback circuits in such systems to aid in the determination of the functionality and integrity of the circuits and of performance margins. The need for this technique arises as follows: Some modern digital systems include feedback circuits that enable other circuits to perform with precision and are tolerant of changes in environment and the device s parameters. For example, in a precision timing circuit, it is desirable to make the circuit insensitive to variability as a result of the manufacture of circuit components and to the effects of temperature, voltage, radiation, and aging. However, such a design can also result in masking the indications of damaged and/or deteriorating components. The present technique incorporates test circuitry and associated engineering-telemetry circuitry into an embedded system to monitor the closed-loop feedback circuits, using spare gates that are often available in field programmable gate arrays (FPGAs). This technique enables a test engineer to determine the amount of performance margin in the system, detect out of family circuit performance, and determine one or more trend(s) in the performance of the system. In one system to which the technique has been applied, an ultra-stable oscillator is used as a reference for internal adjustment of 12 time-to-digital converters (TDCs). The feedback circuit produces a pulse-width-modulated signal that is fed as a control input into an amplifier, which controls the circuit s operating voltage. If the circuit s gates are determined to be operating too slowly or rapidly when their timing is compared with that of the reference signal, then the pulse width increases or decreases, respectively, thereby commanding the amplifier to increase or reduce, respectively, its output level, and "adjust" the speed of the circuits. The nominal frequency of the TDC s pulse width modulated outputs is approximately 40 kHz. In this system, the technique is implemented by means of a monitoring circuit that includes a 20-MHz sampling circuit and a 24-bit accumulator with a gate time of 10 ms. The monitoring circuit measures the duty cycle of each of the 12 TDCs at a repetition rate of 28 Hz. The accumulator content is reset to all zeroes at the beginning of each measurement period and is then incremented or decremented based of the value of the state of the pulse width modulated signal. Positive or negative values in the accumulator correspond to duty cycles greater or less, respectively, than 50 percent.

  4. UWB communication receiver feedback loop

    DOEpatents

    Spiridon, Alex; Benzel, Dave; Dowla, Farid U.; Nekoogar, Faranak; Rosenbury, Erwin T.

    2007-12-04

    A novel technique and structure that maximizes the extraction of information from reference pulses for UWB-TR receivers is introduced. The scheme efficiently processes an incoming signal to suppress different types of UWB as well as non-UWB interference prior to signal detection. Such a method and system adds a feedback loop mechanism to enhance the signal-to-noise ratio of reference pulses in a conventional TR receiver. Moreover, sampling the second order statistical function such as, for example, the autocorrelation function (ACF) of the received signal and matching it to the ACF samples of the original pulses for each transmitted bit provides a more robust UWB communications method and system in the presence of channel distortions.

  5. Recurrent Feedback Loops in Associative Learning.

    PubMed

    Person, Abigail L; Khodakhah, Kamran

    2016-02-01

    In this issue of Neuron, Gao et al. (2016) report on a little-studied feedback pathway from the cerebellar nuclei back to the cerebellar cortex. They find that it contributes to associative conditioning and execution of learned movements, highlighting a role for local feedback loops in the brain. PMID:26844826

  6. Linear phase demodulator including a phase locked loop with auxiliary feedback loop

    NASA Technical Reports Server (NTRS)

    Rippy, R. R. (Inventor)

    1976-01-01

    A phase modulated wave that may have no carrier power is demodulated by a phase locked loop including a phase detector for deriving an A.C. data output signal having a magnitude and a phase indicative of the phase of the modulated wave. A feedback loop responsive to the data output signal restores power to the carrier frequency component to the loop. In one embodiment, the feedback loop includes a phase modulator responsive to the phase modulated wave and the data output signal. In a second embodiment, carrier frequency power is restored by differentiating the data output signal and supplying the differentiated signal to an input of a voltage controlled oscillator included in the phase locked loop.

  7. Closing the Feedback Loop Is Not Enough: The Assessment Spiral

    ERIC Educational Resources Information Center

    Wehlburg, Catherine M.

    2007-01-01

    For quite some time, the call to close the feedback loop has been heard throughout higher education. Faculty and administrators have paid attention, and now they can more easily than ever point to the fact that at their institution, the feedback loop is almost always closed. As reviewers from accreditation teams visit campuses, they often hear…

  8. Modeling and simulation of the second feedback loop for fiber optic gyroscope

    NASA Astrophysics Data System (ADS)

    Zhang, Yong-gang; Gao, Zhong-xing; Wang, Guo-chen; Gao, Wei

    2013-08-01

    Current research on modeling of fiber optic gyroscope (FOG) is mainly concentrate on single digital closed loop FOG under square-wave modulation and demodulation. Little work has been done in modeling and simulation of the second feedback loop of FOG under four-state modulation and demodulation. However, the second feedback loop is very important in improving FOG performance. In order to improve the accuracy and stability more efficient, it's essential to modeling and does simulation of the second feedback loop for fiber optic gyroscope especially in the field of high precision application. There are three major contributions in this paper. Firstly, the physical model of digital closed loop fiber optic gyroscope is built and the scale factor error of FOG due to gain error is derived in theory. The gain error including half-wave voltage change and driver circuit gain change are mainly caused by temperature fluctuation in practical environment. To solve this problem, the second feedback loop based on four-state modulation and demodulation method is provided, and the control model of this method is then set up theoretically by means of transfer function. In the end, simulation of the second feedback loop of FOG is performed by Labview to demonstrate the efficiency of this method. According to our theoretical analysis of the control model and the simulation result, this method can track and compensate the variation of driver circuit gain and half-wave voltage in real-time. Therefore, the nonlinear error of FOG scale factor is reduced by the control of the second feedback loop, which leads to improvement of FOG accuracy.

  9. Linking Nutrients to Growth through a Positive Feedback Loop

    PubMed Central

    Palu, Rebecca A.S.; Thummel, Carl S.

    2016-01-01

    In this issue of Developmental Cell, Okamoto and Nishimura (2015) identify a positive feedback loop between neuronal cells that maintains insulin signaling and growth under restricted nutritional conditions. PMID:26555046

  10. Virtual Grasping: Closed-Loop Force Control Using Electrotactile Feedback

    PubMed Central

    Jorgovanovic, Nikola; Dosen, Strahinja; Djozic, Damir J.; Krajoski, Goran; Farina, Dario

    2014-01-01

    Closing the control loop by providing somatosensory feedback to the user of a prosthesis is a well-known, long standing challenge in the field of prosthetics. Various approaches have been investigated for feedback restoration, ranging from direct neural stimulation to noninvasive sensory substitution methods. Although there are many studies presenting closed-loop systems, only a few of them objectively evaluated the closed-loop performance, mostly using vibrotactile stimulation. Importantly, the conclusions about the utility of the feedback were partly contradictory. The goal of the current study was to systematically investigate the capability of human subjects to control grasping force in closed loop using electrotactile feedback. We have developed a realistic experimental setup for virtual grasping, which operated in real time, included a set of real life objects, as well as a graphical and dynamical model of the prosthesis. We have used the setup to test 10 healthy, able bodied subjects to investigate the role of training, feedback and feedforward control, robustness of the closed loop, and the ability of the human subjects to generalize the control to previously “unseen” objects. Overall, the outcomes of this study are very optimistic with regard to the benefits of feedback and reveal various, practically relevant, aspects of closed-loop control. PMID:24516504

  11. A dynamic-biased dual-loop-feedback CMOS LDO regulator with fast transient response

    NASA Astrophysics Data System (ADS)

    Han, Wang; Maomao, Sun

    2014-04-01

    This paper presents a low-dropout regulator (LDO) for portable applications with dual-loop feedback and a dynamic bias circuit. The dual-loop feedback structure is adopted to reduce the output voltage spike and the response time of the LDO. The dynamic bias circuit enhances the slew rate at the gate of the power transistor. In addition, an adaptive miller compensation technique is employed, from which a single pole system is realized and over a 59° phase margin is achieved under the full range of the load current. The proposed LDO has been implemented in a 0.6-μm CMOS process. From the experimental results, the regulator can operate with a minimum dropout voltage of 200 mV at a maximum 300 mA load and IQ of 113 μA. The line regulation and load regulation are improved to 0.1 mV/V and 3.4 μV/mA due to the sufficient loop gain provided by the dual feedback loops. Under a full range load current step, the voltage spikes and the recovery time of the proposed LDO is reduced to 97 mV and 0.142 μs respectively.

  12. An Analysis Method of Operation State for Boost Converter with Voltage Feedback Control

    NASA Astrophysics Data System (ADS)

    Zhaoxia, Leng; Qingfeng, Liu; Jinkun, Sun; Huamin, Wang

    When system parameters were adjusted, some instability phenomenon could occur in closed-loop DC-DC converter. For improving the stability of converter system, an analysis method of operation state for converter was presented based on the discrete model of continuous conduction mode(CCM) Boost converter with voltage feedback control. This method can avoid fussy derivative operation. The steady equation of CCM Boost converter was deduced and the system parameters condition on which closed-loop instability phenomenon would occur were analyzed, the condition is appropriate to high frequency Boost converter. Corresponding simulation results were given in this paper.

  13. Feedback Control Systems Loop Shaping Design with Practical Considerations

    NASA Technical Reports Server (NTRS)

    Kopsakis, George

    2007-01-01

    This paper describes loop shaping control design in feedback control systems, primarily from a practical stand point that considers design specifications. Classical feedback control design theory, for linear systems where the plant transfer function is known, has been around for a long time. But it s still a challenge of how to translate the theory into practical and methodical design techniques that simultaneously satisfy a variety of performance requirements such as transient response, stability, and disturbance attenuation while taking into account the capabilities of the plant and its actuation system. This paper briefly addresses some relevant theory, first in layman s terms, so that it becomes easily understood and then it embarks into a practical and systematic design approach incorporating loop shaping design coupled with lead-lag control compensation design. The emphasis is in generating simple but rather powerful design techniques that will allow even designers with a layman s knowledge in controls to develop effective feedback control designs.

  14. AC loop voltages and MHD stability in RFP plasmas

    NASA Astrophysics Data System (ADS)

    McCollam, K. J.; Holly, D. J.; Mirnov, V. V.; Sarff, J. S.; Stone, D. R.

    2012-10-01

    Applied AC loop voltages provide a means to study and control the dynamics of MHD activity in RFP plasmas. In MST experiments with a new programmable power supply, applying a poloidal loop voltage oscillation of sufficient amplitude is observed to tightly entrain the ambient quasiperiodic sawtooth magnetic-relaxation cycle in the RFP, making it almost strictly periodic. The RFP's limit-cycle trajectory in (F, θ) space, where F and θ are the equilibrium reversal and pinch parameters, is drastically modified and suggests a fundamentally different relaxation regime. Applying both poloidal and toroidal AC loop voltages, as in oscillating-field current drive (OFCD), changes the limit cycle and can reduce MHD fluctuation amplitudes. The MHD response in OFCD experiments with varying source amplitudes and phase lags is examined in terms of linear stability and nonlinear mode coupling. Linear stability for MHD current-driven modes is calculated in cylindrical geometry, including the effect of conducting-wall proximity, and preliminary results indicate the presence of a stable region in (F, θ) space, consistent with past results for the RFP. By using OFCD to control the RFP's positioning in (F, θ) space, it might be possible to control or suppress MHD activity while driving steady-state plasma current.

  15. Closed loop control of dielectric elastomer actuators based on self-sensing displacement feedback

    NASA Astrophysics Data System (ADS)

    Rizzello, G.; Naso, D.; York, A.; Seelecke, S.

    2016-03-01

    This paper describes a sensorless control algorithm for a positioning system based on a dielectric elastomer actuator (DEA). The voltage applied to the membrane and the resulting current can be measured during the actuation and used to estimate its displacement, i.e., to perform self-sensing. The estimated displacement can be then used as a feedback signal for a position control algorithm, which results in a compact device capable of operating in closed loop control without the need for additional electromechanical or optical transducers. In this work, a circular DEA preloaded with a bi-stable spring is used as a case of study to validate the proposed control architecture. A comparison of the closed loop performance achieved using an accurate laser displacement sensor for feedback is also provided to better assess the performance limitations of the overall sensorless scheme.

  16. The Impact of Hypervigilance: Evidence for a Forward Feedback Loop

    PubMed Central

    Kimble, Matthew; Boxwala, Mariam; Bean, Whitney; Maletsky, Kristin; Halper, Jessica; Spollen, Kaleigh; Fleming, Kevin

    2014-01-01

    A number of prominent theories suggest that hypervigilance and attentional bias play a central role in anxiety disorders and PTSD. It is argued that hypervigilance may focus attention on potential threats and precipitate or maintain a forward feedback loop in which anxiety is increased. While there is considerable data to suggest that attentional bias exists, there is little evidence to suggest that it plays this proposed but critical role. This study investigated how manipulating hypervigilance would impact the forward feedback loop via self-reported anxiety, visual scanning, and pupil size. Seventy-one participants were assigned to either a hypervigilant, pleasant, or control condition while looking at a series of neutral pictures. Those in the hypervigilant condition had significantly more fixations than those in the other two groups. These fixations were more spread out and covered a greater percentage of the ambiguous scene. Pupil size was also significantly larger in the hypervigilant condition relative to the control condition. Thus the study provided support for the role of hypervigilance in increasing visual scanning and arousal even to neutral stimuli and even when there is no change in self-reported anxiety. Implications for the role this may play in perpetuating a forward feedback loop is discussed. PMID:24507631

  17. Concepts in MDM2 Signaling: Allosteric Regulation and Feedback Loops.

    PubMed

    Ponnuswamy, Anand; Hupp, Ted; Fåhraeus, Robin

    2012-03-01

    The function and regulation of MDM2 as a component of a p53-dependent negative feedback loop has formed a core paradigm in the p53 field. This concept, now 20 years old, has been solidified by fields of protein science, transgenic technology, and drug discovery in human cancer. However, it has been noted that a simple negative feedback loop between p53 and MDM2 lacks an intrinsic "activating" step that counteracts this inhibition and permits oscillation of the feedback to occur as p53 is switched on and off. More recent work has identified a solution to the missing piece of the picture that counters the negative feedback loop, which is MDM2 itself. Under conditions of genotoxic stress, MDM2 helps to activate p53 by increasing its rate of protein synthesis. This simple observation makes certain aspects of the p53 response more comprehensible such as why MDM2 is upregulated by p53 early on following DNA damage and how phosphorylation of MDM2 at the C-terminal Ser395 by ATM translates into p53 activation. The latter acts by inducing allosteric changes in the RING domain of MDM2 that expose its RNA binding pocket, support p53 synthesis, and suppress its degradation. This allosteric nature of MDM2 in the C-terminus mirrors the allosteric effects of the binding of small molecules to the p53 interacting pocket at the N-terminus of MDM2, which opens the core domain of MDM2 to central domains of p53, which controls p53 ubiquitination. Thus, the highly allosteric nature of MDM2 provides the basis for dynamic protein-protein interactions and protein-RNA interactions through which MDM2's activity is regulated in p53 protein destruction or in p53 protein synthesis. We discuss these mechanisms and how this information can be exploited for drug development programs aimed at activating p53 via targeting MDM2. PMID:23150762

  18. System identification from closed-loop data with known output feedback dynamics

    NASA Technical Reports Server (NTRS)

    Phan, Minh; Juang, Jer-Nan; Horta, Lucas G.; Longman, Richard W.

    1992-01-01

    This paper presents a procedure to identify the open loop systems when it is operating under closed loop conditions. First, closed loop excitation data are used to compute the system open loop and closed loop Markov parameters. The Markov parameters, which are the pulse response samples, are then used to compute a state space representation of the open loop system. Two closed loop configurations are considered in this paper. The closed loop system can have either a linear output feedback controller or a dynamic output feedback controller. Numerical examples are provided to illustrate the proposed closed loop identification method.

  19. Coupling between feedback loops in autoregulatory networks affects bistability range, open-loop gain and switching times

    PubMed Central

    Tiwari, Abhinav; Igoshin, Oleg A.

    2012-01-01

    Biochemical regulatory networks governing diverse cellular processes such as stress-response, differentiation and cell cycle often contain coupled feedback loops. We aim to understand how features of feedback architecture, such as the number of loops, the sign of the loops and the type of their coupling, affect network dynamical performance. Specifically, we investigate how bistability range, maximum open-loop gain and switching times of a network with transcriptional positive feedback are affected by additive or multiplicative coupling with another positive or negative feedback loop. We show that a network’s bistability range is positively correlated with its maximum open-loop gain and that both the quantities depend on the sign of the feedback loops and the type of feedback coupling. Moreover, we find that the addition of positive feedback could decrease the bistability range if we control the basal level in the signal-response curves of the two systems. Furthermore, the addition of negative feedback has the capacity to increase the bistability range if its dissociation constant is much lower than that of the positive feedback. We also find that addition of a positive feedback to a bistable network increases robustness of its bistability range, whereas addition of a negative feedback decreases it. Finally, we show that the switching time for a transition from a high to a low steady state increases with the effective fold change in gene regulation. In summary, we show that the effect of coupled feedback loops on the bistability range and switching times depends on the underlying mechanistic details. PMID:23011599

  20. Power flow control based solely on slow feedback loop for heart pump applications.

    PubMed

    Wang, Bob; Hu, Aiguo Patrick; Budgett, David

    2012-06-01

    This paper proposes a new control method for regulating power flow via transcutaneous energy transfer (TET) for implantable heart pumps. Previous work on power flow controller requires a fast feedback loop that needs additional switching devices and resonant capacitors to be added to the primary converter. The proposed power flow controller eliminates these additional components, and it relies solely on a slow feedback loop to directly drive the primary converter to meet the heart pump power demand and ensure zero voltage switching. A controlled change in switching frequency varies the resonant tank shorting period of a current-fed push-pull resonant converter, thus changing the magnitude of the primary resonant voltage, as well as the tuning between primary and secondary resonant tanks. The proposed controller has been implemented successfully using an analogue circuit and has reached an end-to-end power efficiency of 79.6% at 10 W with a switching frequency regulation range of 149.3 kHz to 182.2 kHz. PMID:23853149

  1. Feedback loops from the Hubble Space Telescope data processing system

    NASA Astrophysics Data System (ADS)

    Fraquelli, Dorothy A.; Arquilla, Richard; Ellis, Tracy; Hamilton, Forrest C.; Holm, Albert; Kochte, Mark

    2002-12-01

    This paper presents an overview of the history and technology by which tools placed in the Hubble Space Telescope (HST) data processing pipeline were used to feedback information on observation execution to the scheduling system and observers. Because the HST is in a relatively low orbit, which imposes a number of constraints upon its observations, it operates in a carefully planned, fully automated mode. To substitute for direct observer involvement available at most ground-based observatories and to provide rapid feedback on failures that might affect future visits, the Space Telescope Science Institute (STScI) gradually evolved a system for screening science and engineering products during pipeline processing. The highly flexible HST data processing system (OPUS) allows tools to be introduced to use the content of FITS keywords to alert production staff to potential telescope and instrument performance failures. Staff members review the flagged data and, if appropriate, notify the observer and the scheduling staff so that they can resolve the problems and possibly repeat the failed observations. This kind of feedback loop represents a case study for other automated data collection systems where rapid response to certain quantifiable events in the data is required. Observatory operations staff can install processes to look for these events either in the production pipeline or in an associated pipeline into which the appropriate data are piped. That process can then be used to notify scientists to evaluate the data and decide upon a response or to automatically initiate a response.

  2. Estimation of the current driven by residual loop voltage in LHCD plasma on EAST Tokamak

    NASA Astrophysics Data System (ADS)

    Zhang, X. M.; Yu, L. M.; Wan, B. N.; Xue, E. B.; Fang, Y.; Shi, K. Y.; EAST Team

    2016-02-01

    The lower hybrid wave current drive (LHCD) is one of the efficient methods of driving the non-inductive current required for Tokamak operating in steady-state. Residual loop voltage exists in Tokamak when the non-inductive current is not fully driven. Residual loop voltage also accelerates the fast electrons generated by the lower hybrid wave (LHW), which can drive extra current and combine with the current driven by the LHW. It is generally difficult to separate these two different components of driven current in the experiment. In this paper, the currents driven by LHCD and residual loop voltage are separated directly by solving the Fokker–Plank equation numerically. The fraction of the current driven by residual loop voltage compared to the current driven by LHW is evaluated on the experimental advanced superconducting tokamak (EAST). The current driven by residual loop voltage is several percent of the currents driven by the LHCD when the residual loop voltage is small, but it increases with the residual loop voltage up to 25% when the residual loop voltage is about 2 V. The hot electrical conductivity is deduced from the net current driven by the residual loop voltage. Its distribution profile is related to the fast electron distribution driven by LHW.

  3. Practical Loop-Shaping Design of Feedback Control Systems

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2010-01-01

    An improved methodology for designing feedback control systems has been developed based on systematically shaping the loop gain of the system to meet performance requirements such as stability margins, disturbance attenuation, and transient response, while taking into account the actuation system limitations such as actuation rates and range. Loop-shaping for controls design is not new, but past techniques do not directly address how to systematically design the controller to maximize its performance. As a result, classical feedback control systems are designed predominantly using ad hoc control design approaches such as proportional integral derivative (PID), normally satisfied when a workable solution is achieved, without a good understanding of how to maximize the effectiveness of the control design in terms of competing performance requirements, in relation to the limitations of the plant design. The conception of this improved methodology was motivated by challenges in designing control systems of the types needed for supersonic propulsion. But the methodology is generally applicable to any classical control-system design where the transfer function of the plant is known or can be evaluated. In the case of a supersonic aerospace vehicle, a major challenge is to design the system to attenuate anticipated external and internal disturbances, using such actuators as fuel injectors and valves, bypass doors, and ramps, all of which are subject to limitations in actuator response, rates, and ranges. Also, for supersonic vehicles, with long slim type of structures, coupling between the engine and the structural dynamics can produce undesirable effects that could adversely affect vehicle stability and ride quality. In order to design distributed controls that can suppress these potential adverse effects, within the full capabilities of the actuation system, it is important to employ a systematic control design methodology such as this that can maximize the effectiveness of the control design in a methodical and quantifiable way. The emphasis is in generating simple but rather powerful design techniques that will allow even designers with a layman s knowledge in controls to develop effective feedback control designs. Unlike conventional ad hoc methodologies of feedback control design, in this approach actuator rates are incorporated into the design right from the start: The relation between actuator speeds and the desired control bandwidth of the system is established explicitly. The technique developed is demonstrated via design examples in a step-by-step tutorial way. Given the actuation system rates and range limits together with design specifications in terms of stability margins, disturbance rejection, and transient response, the procedure involves designing the feedback loop gain to meet the requirements and maximizing the control system effectiveness, without exceeding the actuation system limits and saturating the controller. Then knowing the plant transfer function, the procedure involves designing the controller so that the controller transfer function together with the plant transfer function equate to the designed loop gain. The technique also shows what the limitations of the controller design are and how to trade competing design requirements such as stability margins and disturbance rejection. Finally, the technique is contrasted against other more familiar control design techniques, like PID control, to show its advantages.

  4. On the dynamics of delayed neural feedback loops

    NASA Astrophysics Data System (ADS)

    Brandt, Sebastian F.

    The computational potential of neural circuits arises from the interconnections and interactions between their elements. Feedback is a universal feature of neuronal organization and has been shown to be a key element in neural signal processing. In biological neural circuits, delays arise from finite axonal conduction speeds and at the synaptic level due to transmitter release dynamics. In this work, the influence of temporal delay on neural network dynamics is investigated. The basic feedback mechanisms involved in the regulation of neural activity consist of small circuits composed of two to three neurons. We analyze a system of two interconnected neurons and show that finite delays can induce oscillations in the system. Employing a perturbative approach in combination with a resummation scheme, we evaluate the limit cycle dynamics of the system. We show that synchronous oscillations can arise when the delays are asymmetric. Furthermore, distributed delays can stabilize the system and lead to an increased range of parameters for which the system converges to a stable fixed point. We next consider a delayed neural triad with a characteristic topology commonly found in neural feedback circuits. We show that the system can be both robust and sensitive in regard to small parameter changes and examine the significance of the different projections We then address the functional role of a particular feedback loop found in the visual system of nonmammalian vertebrates. We show that the system can function as a 'winner-take-all' and novelty detector and examine the influence of temporal delays on the system's performance. Biological systems are subject to stochastic influences and display some degree of disorder. We examine the role of noise and its effect on the stability of the synchronized state in a system of two coupled active rotators. Finally, we show that disordering the driving forces in arrays of coupled oscillators can lead to synchronization in these systems.

  5. Experimental Feedback on Sodium Loop Decommissioning at the CEA

    SciTech Connect

    Vinoche, O.; Rodriguez, G.

    2002-07-01

    The aim of this paper is to present experimental feedback on sodium loop dismantling techniques at the CEA (The French Atomic Energy Commission) and to offer recommendations for the decommissioning of Fast Breeder Reactor secondary sodium loops. This study is divided into several parts which correspond to the different stages of a dismantling system. It is based on acquired CEA decommissioning experience which primarily concerns the following: the decommissioning of Rapsodie (France's first Fast Breeder Reactor), the Phenix reactor secondary loop replacement, the sodium loop decommissioning carried out by the Laboratory of Sodium Technologies and Treatment, and several technical documents. This paper deals with the main results of this survey. First, a comparison of 8 pipe-cutting techniques is made, taking into account speed in cutting, reliability, dissemination, fire risk due to the presence of sodium, cutting depth, and different types of waste (empty pipes, sodium-filled pipes, tanks...). This comparison has led us to recommend the use of an alternative saw or a chain saw rather than the use of the plasma torch or grinder. Different techniques are recommended depending on if they are on-site, initial cuttings or if they are to be carried out in a specially-designed facility referred to hereafter as 'the cutting building'. After the cutting stage, the sodium waste must be processed with water to become an ultimate stable waste. Four treatment processes are compared with different standards: speed, cost, low activity adaptability and 'large sodium quantity' adaptability. Recommendations are also made for reliable storage, and for the general dismantling system organization. Last, calculations are presented concerning a complete dismantling facility prototype capable of treating large amounts of sodium. (authors)

  6. The neural feedback loop between the brain and adipose tissues.

    PubMed

    Pnicaud, Luc

    2010-01-01

    There are more and more data supporting the importance of nervous regulation of both white and brown adipose tissue mass. This short paper will review the different physiological parameters which are regulated such as metabolism (lipolysis and thermogeneis), secretory activity (leptin and other adipokines) but also to plasticity of adipose tissues (proliferation differentiation and apoptosis). The sensory innervation of white adipose issue and its putative role will be also described. Altogether these results showed the presence of a neural feedback loop between adipose tissues and the brain which plays a major role in the regulation of energy homeostasis and has been shown to be altered in physiologic as well as in metabolic pathologies. PMID:20551671

  7. A Moral Experience Feedback Loop: Modeling a System of Moral Self-Cultivation in Everyday Life

    ERIC Educational Resources Information Center

    Sherblom, Stephen A.

    2015-01-01

    This "systems thinking" model illustrates a common feedback loop by which people engage the moral world and continually reshape their moral sensibility. The model highlights seven processes that collectively form this feedback loop: beginning with (1) one's current moral sensibility which shapes processes of (2) perception, (3)

  8. A Moral Experience Feedback Loop: Modeling a System of Moral Self-Cultivation in Everyday Life

    ERIC Educational Resources Information Center

    Sherblom, Stephen A.

    2015-01-01

    This "systems thinking" model illustrates a common feedback loop by which people engage the moral world and continually reshape their moral sensibility. The model highlights seven processes that collectively form this feedback loop: beginning with (1) one's current moral sensibility which shapes processes of (2) perception, (3)…

  9. Possible precursors of ball lightning. Observation of closed loops in high voltage discharges

    SciTech Connect

    Alexeff, I.; Rader, M.

    1995-05-01

    Several hundred photographs of ultrahigh voltage discharges have been obtained that show closed current loops. These closed current loops may be precursors of ball lightning. One feature of these discharges may explain why observations of ball lightning may be infrequent; that is, there is a distinct threshold in voltage and/or current below which the closed loops do not occur. This threshold current fits other experimental data but is well above the usually observed currents in natural lightning. 10 refs., 3 figs.

  10. Interlinked Fast and Slow Positive Feedback Loops Drive Reliable Cell Decisions

    NASA Astrophysics Data System (ADS)

    Brandman, Onn; Ferrell, James E.; Li, Rong; Meyer, Tobias

    2005-10-01

    Positive feedback is a ubiquitous signal transduction motif that allows systems to convert graded inputs into decisive, all-or-none outputs. Here we investigate why the positive feedback switches that regulate polarization of budding yeast, calcium signaling, Xenopus oocyte maturation, and various other processes use multiple interlinked loops rather than single positive feedback loops. Mathematical simulations revealed that linking fast and slow positive feedback loops creates a ``dual-time'' switch that is both rapidly inducible and resistant to noise in the upstream signaling system.

  11. Oscillating holograms recorded in photorefractive crystals by a frequency detuned feedback loop

    NASA Astrophysics Data System (ADS)

    Freschi, A. A.; Telles, A. C. C.; Frejlich, J.; Donatti, D. A.

    2009-01-01

    We report an optoelectronic feedback loop suitable for generating noise-free interference patterns oscillating at arbitrary waveforms. The technique allows controlling the frequency detuning between the interfering beams through a phase modulator in a closed-loop interferometer. We use the dither signal method and propose a quasisynchronous demodulation scheme to create a phase modulated error signal for driving the loop. The dynamics of the interference fringes is easily controlled by a voltage waveform from a function generator, which is used in association with a time delay circuit for shifting the frequency of the reference signal used for lock-in demodulation. The technique is specially suited for applications involving low-frequency phase oscillations, such as those frequently encountered in the generation of space-charge waves in highly resistive photorefractive materials. The processing scheme allows real time monitoring of the hologram strength, and absolute values for the diffraction efficiency and the holographic phase shift can be obtained. Photorefractive wave oscillations ranging from approximately 100 mHz to 10 Hz were produced in a nominally undoped Bi12TiO20 sample. The technique can be readily applied to other fields of optical interferometry, such as for testing optical surfaces, optimizing adaptive holographic devices, measuring physical quantities, among other applications.

  12. A Feedback Loop between Inflammation and Zn Uptake

    PubMed Central

    Bonaventura, Paola; Lamboux, Aline; Albarède, Francis; Miossec, Pierre

    2016-01-01

    Objective Zinc (Zn) has major effects on the immune system and inflammation is associated with systemic Zn deficiency. The aim of this work was to investigate how inflammation modifies Zn metabolism at the cellular level. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a model of chronic inflammation. Osteoarthritis (OA) synoviocytes were used as control. Methods Zn levels were measured in medium and inside cells by Induced Coupled Plasma-Mass Spectrometry (ICP-MS), in the presence of minute quantities of stable spike 70Zn isotope and the addition or not of the pro-inflammatory cytokines interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α). Gene expression of ZIP-8 importer, ZnT1 exporter and the homeostasis regulators metallothioneins (MTs) was evaluated after pre-exposure to cytokines, with or without exogenous Zn addition at increasing concentrations. IL-6 production was used as a marker of inflammation and measured by ELISA. Results Exposure to IL-17 and TNF-α enhanced expression of the Zn-importer ZIP-8, regardless of the concentration of Zn in the culture medium. In contrast, the expression of the Zn-exporter ZnT1 and of the MTs was primarily dependent on Zn levels. Addition of Zn also increased the production of IL-6, thus further stimulating the inflammatory response. Conclusion IL-17/TNF-mediated inflammation enhanced the intracellular Zn uptake by synoviocytes, further increasing inflammation. These observations document the existence of a feedback loop between inflammation and Zn uptake. Based on these results, a mathematical model was developed to represent the cytokine-mediated Zn homeostasis alterations. PMID:26845700

  13. Modular high-voltage bias generator powered by dual-looped self-adaptive wireless power transmission.

    PubMed

    Xie, Kai; Huang, An-Feng; Li, Xiao-Ping; Guo, Shi-Zhong; Zhang, Han-Lu

    2015-04-01

    We proposed a modular high-voltage (HV) bias generator powered by a novel transmitter-sharing inductive coupled wireless power transmission technology, aimed to extend the generator's flexibility and configurability. To solve the problems caused through an uncertain number of modules, a dual-looped self-adaptive control method is proposed that is capable of tracking resonance frequency while maintaining a relatively stable induction voltage for each HV module. The method combines a phase-locked loop and a current feedback loop, which ensures an accurate resonance state and a relatively constant boost ratio for each module, simplifying the architecture of the boost stage and improving the total efficiency. The prototype was built and tested. The input voltage drop of each module is less than 14% if the module number varies from 3 to 10; resonance tracking is completed within 60 ms. The efficiency of the coupling structure reaches up to 95%, whereas the total efficiency approaches 73% for a rated output. Furthermore, this technology can be used in various multi-load wireless power supply applications. PMID:25933880

  14. Modular high-voltage bias generator powered by dual-looped self-adaptive wireless power transmission

    NASA Astrophysics Data System (ADS)

    Xie, Kai; Huang, An-Feng; Li, Xiao-Ping; Guo, Shi-Zhong; Zhang, Han-Lu

    2015-04-01

    We proposed a modular high-voltage (HV) bias generator powered by a novel transmitter-sharing inductive coupled wireless power transmission technology, aimed to extend the generator's flexibility and configurability. To solve the problems caused through an uncertain number of modules, a dual-looped self-adaptive control method is proposed that is capable of tracking resonance frequency while maintaining a relatively stable induction voltage for each HV module. The method combines a phase-locked loop and a current feedback loop, which ensures an accurate resonance state and a relatively constant boost ratio for each module, simplifying the architecture of the boost stage and improving the total efficiency. The prototype was built and tested. The input voltage drop of each module is less than 14% if the module number varies from 3 to 10; resonance tracking is completed within 60 ms. The efficiency of the coupling structure reaches up to 95%, whereas the total efficiency approaches 73% for a rated output. Furthermore, this technology can be used in various multi-load wireless power supply applications.

  15. Robustness of the bistable behavior of a biological signaling feedback loop

    NASA Astrophysics Data System (ADS)

    Bhalla, Upinder S.; Iyengar, Ravi

    2001-03-01

    Biological signaling networks comprised of cellular components including signaling proteins and small molecule messengers control the many cell function in responses to various extracellular and intracellular signals including hormone and neurotransmitter inputs, and genetic events. Many signaling pathways have motifs familiar to electronics and control theory design. Feedback loops are among the most common of these. Using experimentally derived parameters, we modeled a positive feedback loop in signaling pathways used by growth factors to trigger cell proliferation. This feedback loop is bistable under physiological conditions, although the system can move to a monostable state as well. We find that bistability persists under a wide range of regulatory conditions, even when core enzymes in the feedback loop deviate from physiological values. We did not observe any other phenomena in the core feedback loop, but the addition of a delayed inhibitory feedback was able to generate oscillations under rather extreme parameter conditions. Such oscillations may not be of physiological relevance. We propose that the kinetic properties of this feedback loop have evolved to support bistability and flexibility in going between bistable and monostable modes, while simultaneously being very refractory to oscillatory states.

  16. Voltage Regulation and Line Loss Minimization of Loop Distribution Systems Using UPFC

    NASA Astrophysics Data System (ADS)

    Sayed, Mahmoud A.; Takeshita, Takaharu

    This paper presents a new method for achieving line loss minimization and voltage regulation in the loop distribution systems, simultaneously. First, mathematical analysis of the line loss minimum conditions in the loop distribution systems is presented. Then, load voltage regulation is applied in the loop distribution system under line loss minimum condition. Reference angle of the desired load voltage is the main factor that can be used to minimize total line loss during load voltage control. In order to achieve these two objectives simultaneously, the UPFC (unified power flow controller), a typical FACTS (flexible AC transmission systems) device, that is capable of instantaneous control of transmission and distribution power flow, is used. Also, the UPFC control scheme to regulate the load voltage under line loss minimization is presented. The effectiveness of the proposed control scheme has been verified experimentally using laboratory prototype in a 200V, 6kVA system.

  17. Inherent directionality explains the lack of feedback loops in empirical networks.

    PubMed

    Domínguez-García, Virginia; Pigolotti, Simone; Muñoz, Miguel A

    2014-01-01

    We explore the hypothesis that the relative abundance of feedback loops in many empirical complex networks is severely reduced owing to the presence of an inherent global directionality. Aimed at quantifying this idea, we propose a simple probabilistic model in which a free parameter γ controls the degree of inherent directionality. Upon strengthening such directionality, the model predicts a drastic reduction in the fraction of loops which are also feedback loops. To test this prediction, we extensively enumerated loops and feedback loops in many empirical biological, ecological and socio-technological directed networks. We show that, in almost all cases, empirical networks have a much smaller fraction of feedback loops than network randomizations. Quite remarkably, this empirical finding is quantitatively reproduced, for all loop lengths, by our model by fitting its only parameter γ. Moreover, the fitted value of γ correlates quite well with another direct measurement of network directionality, performed by means of a novel algorithm. We conclude that the existence of an inherent network directionality provides a parsimonious quantitative explanation for the observed lack of feedback loops in empirical networks. PMID:25531727

  18. Inherent directionality explains the lack of feedback loops in empirical networks

    PubMed Central

    Domínguez-García, Virginia; Pigolotti, Simone; Muñoz, Miguel A.

    2014-01-01

    We explore the hypothesis that the relative abundance of feedback loops in many empirical complex networks is severely reduced owing to the presence of an inherent global directionality. Aimed at quantifying this idea, we propose a simple probabilistic model in which a free parameter γ controls the degree of inherent directionality. Upon strengthening such directionality, the model predicts a drastic reduction in the fraction of loops which are also feedback loops. To test this prediction, we extensively enumerated loops and feedback loops in many empirical biological, ecological and socio-technological directed networks. We show that, in almost all cases, empirical networks have a much smaller fraction of feedback loops than network randomizations. Quite remarkably, this empirical finding is quantitatively reproduced, for all loop lengths, by our model by fitting its only parameter γ. Moreover, the fitted value of γ correlates quite well with another direct measurement of network directionality, performed by means of a novel algorithm. We conclude that the existence of an inherent network directionality provides a parsimonious quantitative explanation for the observed lack of feedback loops in empirical networks. PMID:25531727

  19. On the periodic coordination of linear stochastic systems. [open-loop and closed-loop feedback optimal control

    NASA Technical Reports Server (NTRS)

    Chong, C.-Y.; Athans, M.

    1975-01-01

    The decentralized stochastic control of a linear dynamic system consisting of several subsystems is considered. A two-level approach is used by the introduction of a coordinator who collects measurements from the local controllers periodically and in return transmits coordinating parameters. Two types of coordination are considered: open-loop feedback and closed loop. The resulting control laws are found to be intuitively attractive.

  20. Positive And Negative Feedback Loops Coupled By Common Transcription Activator And Repressor

    NASA Astrophysics Data System (ADS)

    Sielewiesiuk, Jan; Łopaciuk, Agata

    2015-03-01

    Dynamical systems consisting of two interlocked loops with negative and positive feedback have been studied using the linear analysis of stability and numerical solutions. Conditions for saddle-node bifurcation were formulated in a general form. Conditions for Hopf bifurcations were found in a few symmetrical cases. Auto-oscillations, when they exist, are generated by the negative feedback repressive loop. This loop determines the frequency and amplitude of oscillations. The positive feedback loop of activation slightly modifies the oscillations. Oscillations are possible when the difference between Hilll's coefficients of the repression and activation is sufficiently high. The highly cooperative activation loop with a fast turnover slows down or even makes the oscillations impossible. The system under consideration can constitute a component of epigenetic or enzymatic regulation network.

  1. An Adapting Auditory-motor Feedback Loop Can Contribute to Generating Vocal Repetition

    PubMed Central

    Brainard, Michael S.; Jin, Dezhe Z.

    2015-01-01

    Consecutive repetition of actions is common in behavioral sequences. Although integration of sensory feedback with internal motor programs is important for sequence generation, if and how feedback contributes to repetitive actions is poorly understood. Here we study how auditory feedback contributes to generating repetitive syllable sequences in songbirds. We propose that auditory signals provide positive feedback to ongoing motor commands, but this influence decays as feedback weakens from response adaptation during syllable repetitions. Computational models show that this mechanism explains repeat distributions observed in Bengalese finch song. We experimentally confirmed two predictions of this mechanism in Bengalese finches: removal of auditory feedback by deafening reduces syllable repetitions; and neural responses to auditory playback of repeated syllable sequences gradually adapt in sensory-motor nucleus HVC. Together, our results implicate a positive auditory-feedback loop with adaptation in generating repetitive vocalizations, and suggest sensory adaptation is important for feedback control of motor sequences. PMID:26448054

  2. An Adapting Auditory-motor Feedback Loop Can Contribute to Generating Vocal Repetition.

    PubMed

    Wittenbach, Jason D; Bouchard, Kristofer E; Brainard, Michael S; Jin, Dezhe Z

    2015-10-01

    Consecutive repetition of actions is common in behavioral sequences. Although integration of sensory feedback with internal motor programs is important for sequence generation, if and how feedback contributes to repetitive actions is poorly understood. Here we study how auditory feedback contributes to generating repetitive syllable sequences in songbirds. We propose that auditory signals provide positive feedback to ongoing motor commands, but this influence decays as feedback weakens from response adaptation during syllable repetitions. Computational models show that this mechanism explains repeat distributions observed in Bengalese finch song. We experimentally confirmed two predictions of this mechanism in Bengalese finches: removal of auditory feedback by deafening reduces syllable repetitions; and neural responses to auditory playback of repeated syllable sequences gradually adapt in sensory-motor nucleus HVC. Together, our results implicate a positive auditory-feedback loop with adaptation in generating repetitive vocalizations, and suggest sensory adaptation is important for feedback control of motor sequences. PMID:26448054

  3. Closing the Feedback Loop? Iterative Feedback between Tutor and Student in Coursework Assessments

    ERIC Educational Resources Information Center

    Barker, Martin; Pinard, Michelle

    2014-01-01

    We evaluate the case for using feedback iteratively, to improve student engagement and learning. In this model, students were invited to respond to tutor feedback with students' own responses. Among the three courses/modules (three tutors) studied, differences in feedback styles were evident from: (a) thematic analysis of tutor comments and,…

  4. Closed Loop Feedback of MHD Instabilities on DIII-D

    SciTech Connect

    Fredrickson, E.D.; Bialek, J.; Garofalo, A.M.; Johnson, L.C.; La Haye, R.J.; Lazarus, E.A.

    2001-01-16

    A system of coils, sensors and amplifiers has been installed on the DIII-D tokamak to study the physics of feedback stabilization of low-frequency MHD [magnetohydrodynamic] modes such as the Resistive Wall Mode (RWM). Experiments are being performed to assess the effectiveness of this minimal system and benchmark the predictions of theoretical models and codes. In the last campaign, the experiments have been extended to a regime where the RWM threshold is lowered by a fast ramp of the plasma current. In these experiments, the onset time of the RWM is very reproducible. With this system, the onset of the RWM has been delayed by up to 100 msec without degrading plasma performance. The growth rate of the mode increases proportional to the length of delay, suggesting that the plasma is evolving towards a more unstable configuration. The present results have suggested directions for improving the feedback system including better sensors and improved feedback algorithms.

  5. In vitro studies of closed-loop feedback and electrosensory processing in Apteronotus leptorhynchus.

    PubMed

    Mileva, Gerri; Zysman, Daniel; Groothuis, Sally; Lewis, John E

    2008-01-01

    Electrosensory systems comprise extensive feedback pathways. It is also well known that these pathways exhibit synaptic plasticity on a wide-range of time scales. Recent in vitro brain slice studies have characterized synaptic plasticity in the two main feedback pathways to the electrosensory lateral line lobe (ELL), a primary electrosensory nucleus in Apteronotus leptorhynchus. Currently-used slice preparations, involving networks in open-loop conditions, allow feedback inputs to be studied in isolation, a critical step in determining their synaptic properties. However, to fully understand electrosensory processing, we must understand how dynamic feedback modulates neuronal responses under closed-loop conditions. To bridge the gap between current in vitro approaches and more complex in vivo work, we present two new in vitro approaches for studying the roles of closed-loop feedback in electrosensory processing. The first involves a hybrid-network approach using dynamic clamp, and the second involves a new slice preparation that preserves one of the feedback pathways to ELL in a closed-loop condition. PMID:18996475

  6. MEMS closed-loop control incorporating a memristor as feedback sensing element

    SciTech Connect

    Garcia, Ernest J.; Almeida, Sergio F.; Mireles, Jr., Jose; Zubia, David

    2015-12-01

    In this work the integration of a memristor with a MEMS parallel plate capacitor coupled by an amplification stage is simulated. It is shown that the MEMS upper plate position can be controlled up to 95% of the total gap. Due to its common operation principle, the change in the MEMS plate position can be interpreted by the change in the memristor resistance, or memristance. A memristance modulation of ~1 KΩ was observed. A polynomial expression representing the MEMS upper plate displacement as a function of the memristance is presented. Thereafter a simple design for a voltage closed-loop control is presented showing that the MEMS upper plate can be stabilized up to 95% of the total gap using the memristor as a feedback sensing element. As a result, the memristor can play important dual roles in overcoming the limited operation range of MEMS parallel plate capacitors and in simplifying read-out circuits of those devices by representing the motion of the upper plate in the form of resistance change instead of capacitance change.

  7. MEMS closed-loop control incorporating a memristor as feedback sensing element

    DOE PAGESBeta

    Garcia, Ernest J.; Almeida, Sergio F.; Mireles, Jr., Jose; Zubia, David

    2015-12-01

    In this work the integration of a memristor with a MEMS parallel plate capacitor coupled by an amplification stage is simulated. It is shown that the MEMS upper plate position can be controlled up to 95% of the total gap. Due to its common operation principle, the change in the MEMS plate position can be interpreted by the change in the memristor resistance, or memristance. A memristance modulation of ~1 KΩ was observed. A polynomial expression representing the MEMS upper plate displacement as a function of the memristance is presented. Thereafter a simple design for a voltage closed-loop control ismore » presented showing that the MEMS upper plate can be stabilized up to 95% of the total gap using the memristor as a feedback sensing element. As a result, the memristor can play important dual roles in overcoming the limited operation range of MEMS parallel plate capacitors and in simplifying read-out circuits of those devices by representing the motion of the upper plate in the form of resistance change instead of capacitance change.« less

  8. Linking Multimodal Communication and Feedback Loops to Reinforce Plagiarism Awareness

    ERIC Educational Resources Information Center

    O'Donnell, Kerri

    2011-01-01

    In this article, the author describes the use of an electronic quiz on a trial basis as a means of improving students' awareness of academic misconduct issues and their understanding of how to avoid those issues. The quiz integrated several new factors into information-sharing processes, increasing feedback to both students and staff. It was by no

  9. Linking Multimodal Communication and Feedback Loops to Reinforce Plagiarism Awareness

    ERIC Educational Resources Information Center

    O'Donnell, Kerri

    2011-01-01

    In this article, the author describes the use of an electronic quiz on a trial basis as a means of improving students' awareness of academic misconduct issues and their understanding of how to avoid those issues. The quiz integrated several new factors into information-sharing processes, increasing feedback to both students and staff. It was by no…

  10. Pulsed phase locked loop strain monitor. [voltage controlled oscillators

    NASA Technical Reports Server (NTRS)

    Heyman, J. S. (Inventor)

    1982-01-01

    The RF output of a voltage controlled oscillator (VCO) is periodically gated to a transducer which produces acoustic waves in a bolt. The reflected acoustic waves are converted to electrical signals by the transducer and gated to a mixer which also receives the output from the VCO and produces an output which is filtered by a low pass filter. The output of filter is a dc signal proportional to the phase difference change from a fixed phase difference between the two input signals to the mixer. This dc signal is sampled at an instant and held by circuit in response to the "P" signal. The output of the circuit is integrated and then applied to the VCO to change the frequency of the VCO such that the phase difference between the two inputs to the mixer remains at the fixed phase difference. The frequency of the VCO is a measure of the change in strain of the bolt.

  11. Linear state feedback, quadratic weights, and closed loop eigenstructures. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Thompson, P. M.

    1979-01-01

    Results are given on the relationships between closed loop eigenstructures, state feedback gain matrices of the linear state feedback problem, and quadratic weights of the linear quadratic regulator. Equations are derived for the angles of general multivariable root loci and linear quadratic optimal root loci, including angles of departure and approach. The generalized eigenvalue problem is used for the first time to compute angles of approach. Equations are also derived to find the sensitivity of closed loop eigenvalues and the directional derivatives of closed loop eigenvectors (with respect to a scalar multiplying the feedback gain matrix or the quadratic control weight). An equivalence class of quadratic weights that produce the same asymptotic eigenstructure is defined, sufficient conditions to be in it are given, a canonical element is defined, and an algorithm to find it is given. The behavior of the optimal root locus in the nonasymptotic region is shown to be different for quadratic weights with the same asymptotic properties.

  12. High alpha feedback control for agile half-loop maneuvers of the F-18 airplane

    NASA Technical Reports Server (NTRS)

    Stalford, Harold

    1988-01-01

    A nonlinear feedback control law for the F/A-18 airplane that provides time-optimal or agile maneuvering of the half-loop maneuver at high angles of attack is given. The feedback control law was developed using the mathematical approach of singular perturbations, in which the control devices considered were conventional aerodynamic control surfaces and thrusting. The derived nonlinear control law was used to simulate F/A-18 half-loop maneuvers. The simulated results at Mach 0.6 and 0.9 compared well with pilot simulations conducted at NASA.

  13. Optimal open-loop and feedback control using single gimbal control moment gyroscopes

    NASA Technical Reports Server (NTRS)

    Hoelscher, Brian R.; Vadali, Srinvas R.

    1993-01-01

    Methods for control of spacecraft maneuvers through the use of single gimbal control moment gyroscopes are developed. The development employs an integrated model of the spacecraft dynamics with the control moment gyroscope dynamics. Smooth and continuous open-loop control profiles are obtained which minimize a weighted function of maneuver time, magnitude of control effort, and proximity to singular gimbal configurations. Closed-loop state feedback control laws are derived by invoking Lyapunov stability theory. The schemes are presented for implementing the commanded state feedback: gimbal rate control and gimbal acceleration control. The appropriate handling of singular gimbal configurations is also discussed.

  14. Depression as a systemic syndrome: mapping the feedback loops of major depressive disorder

    PubMed Central

    Wittenborn, A. K.; Rahmandad, H.; Rick, J.; Hosseinichimeh, N.

    2016-01-01

    Background Depression is a complex public health problem with considerable variation in treatment response. The systemic complexity of depression, or the feedback processes among diverse drivers of the disorder, contribute to the persistence of depression. This paper extends prior attempts to understand the complex causal feedback mechanisms that underlie depression by presenting the first broad boundary causal loop diagram of depression dynamics. Method We applied qualitative system dynamics methods to map the broad feedback mechanisms of depression. We used a structured approach to identify candidate causal mechanisms of depression in the literature. We assessed the strength of empirical support for each mechanism and prioritized those with support from validation studies. Through an iterative process, we synthesized the empirical literature and created a conceptual model of major depressive disorder. Results The literature review and synthesis resulted in the development of the first causal loop diagram of reinforcing feedback processes of depression. It proposes candidate drivers of illness, or inertial factors, and their temporal functioning, as well as the interactions among drivers of depression. The final causal loop diagram defines 13 key reinforcing feedback loops that involve nine candidate drivers of depression. Conclusions Future research is needed to expand upon this initial model of depression dynamics. Quantitative extensions may result in a better understanding of the systemic syndrome of depression and contribute to personalized methods of evaluation, prevention and intervention. PMID:26621339

  15. Closing the Feedback Loop: Physics Undergraduates' Use of Feedback Comments on Laboratory Coursework

    ERIC Educational Resources Information Center

    Donovan, Pam

    2014-01-01

    The laboratory notebooks of physics undergraduates taking two second-year practical courses were audited to discover whether they had used feedback comments in their subsequent coursework. Ninety-five per cent of the 37 students on the first course and 100% of the 14 students on the second course whose work was audited had used feedback. The…

  16. Modeling of bovine spongiform encephalopathy in a two-species feedback loop.

    PubMed

    Barnes, Richard; Lehman, Clarence

    2013-06-01

    Bovine spongiform encephalopathy, otherwise known as mad cow disease, can spread when an individual cow consumes feed containing the infected tissues of another individual, forming a one-species feedback loop. Such feedback is the primary means of transmission for BSE during epidemic conditions. Following outbreaks in the European Union and elsewhere, many governments enacted legislation designed to limit the spread of such diseases via elimination or reduction of one-species feedback loops in agricultural systems. However, two-species feedback loops-those in which infectious material from one-species is consumed by a secondary species whose tissue is then consumed by the first species-were not universally prohibited and have not been studied before. Here we present a basic ecological disease model which examines the rôle feedback loops may play in the spread of BSE and related diseases. Our model shows that there are critical thresholds between the infection's expansion and decrease related to the lifespan of the hosts, the growth rate of the prions, and the amount of prions circulating between hosts. The ecological disease dynamics can be intrinsically oscillatory, having outbreaks as well as refractory periods which can make it appear that the disease is under control while it is still increasing. We show that non-susceptible species that have been intentionally inserted into a feedback loop to stop the spread of disease do not, strictly by themselves, guarantee its control, though they may give that appearance by increasing the refractory period of an epidemic's oscillations. We suggest ways in which age-related dynamics and cross-species coupling should be considered in continuing evaluations aimed at maintaining a safe food supply. PMID:23746801

  17. The role of feed-forward and feedback processes for closed-loop prosthesis control

    PubMed Central

    2011-01-01

    Background It is widely believed that both feed-forward and feed-back mechanisms are required for successful object manipulation. Open-loop upper-limb prosthesis wearers receive no tactile feedback, which may be the cause of their limited dexterity and compromised grip force control. In this paper we ask whether observed prosthesis control impairments are due to lack of feedback or due to inadequate feed-forward control. Methods Healthy subjects were fitted with a closed-loop robotic hand and instructed to grasp and lift objects of different weights as we recorded trajectories and force profiles. We conducted three experiments under different feed-forward and feed-back configurations to elucidate the role of tactile feedback (i) in ideal conditions, (ii) under sensory deprivation, and (iii) under feed-forward uncertainty. Results (i) We found that subjects formed economical grasps in ideal conditions. (ii) To our surprise, this ability was preserved even when visual and tactile feedback were removed. (iii) When we introduced uncertainty into the hand controller performance degraded significantly in the absence of either visual or tactile feedback. Greatest performance was achieved when both sources of feedback were present. Conclusions We have introduced a novel method to understand the cognitive processes underlying grasping and lifting. We have shown quantitatively that tactile feedback can significantly improve performance in the presence of feed-forward uncertainty. However, our results indicate that feed-forward and feed-back mechanisms serve complementary roles, suggesting that to improve on the state-of-the-art in prosthetic hands we must develop prostheses that empower users to correct for the inevitable uncertainty in their feed-forward control. PMID:22032545

  18. Maxwell's demon in biochemical signal transduction with feedback loop

    PubMed Central

    Ito, Sosuke; Sagawa, Takahiro

    2015-01-01

    Signal transduction in living cells is vital to maintain life itself, where information transfer in noisy environment plays a significant role. In a rather different context, the recent intensive research on ‘Maxwell's demon'—a feedback controller that utilizes information of individual molecules—have led to a unified theory of information and thermodynamics. Here we combine these two streams of research, and show that the second law of thermodynamics with information reveals the fundamental limit of the robustness of signal transduction against environmental fluctuations. Especially, we find that the degree of robustness is quantitatively characterized by an informational quantity called transfer entropy. Our information-thermodynamic approach is applicable to biological communication inside cells, in which there is no explicit channel coding in contrast to artificial communication. Our result could open up a novel biophysical approach to understand information processing in living systems on the basis of the fundamental information–thermodynamics link. PMID:26099556

  19. Maxwell's demon in biochemical signal transduction with feedback loop.

    PubMed

    Ito, Sosuke; Sagawa, Takahiro

    2015-01-01

    Signal transduction in living cells is vital to maintain life itself, where information transfer in noisy environment plays a significant role. In a rather different context, the recent intensive research on 'Maxwell's demon'-a feedback controller that utilizes information of individual molecules-have led to a unified theory of information and thermodynamics. Here we combine these two streams of research, and show that the second law of thermodynamics with information reveals the fundamental limit of the robustness of signal transduction against environmental fluctuations. Especially, we find that the degree of robustness is quantitatively characterized by an informational quantity called transfer entropy. Our information-thermodynamic approach is applicable to biological communication inside cells, in which there is no explicit channel coding in contrast to artificial communication. Our result could open up a novel biophysical approach to understand information processing in living systems on the basis of the fundamental information-thermodynamics link. PMID:26099556

  20. Maxwell's demon in biochemical signal transduction with feedback loop

    NASA Astrophysics Data System (ADS)

    Ito, Sosuke; Sagawa, Takahiro

    2015-06-01

    Signal transduction in living cells is vital to maintain life itself, where information transfer in noisy environment plays a significant role. In a rather different context, the recent intensive research on `Maxwell's demon'--a feedback controller that utilizes information of individual molecules--have led to a unified theory of information and thermodynamics. Here we combine these two streams of research, and show that the second law of thermodynamics with information reveals the fundamental limit of the robustness of signal transduction against environmental fluctuations. Especially, we find that the degree of robustness is quantitatively characterized by an informational quantity called transfer entropy. Our information-thermodynamic approach is applicable to biological communication inside cells, in which there is no explicit channel coding in contrast to artificial communication. Our result could open up a novel biophysical approach to understand information processing in living systems on the basis of the fundamental information-thermodynamics link.

  1. A Learning Progression for Feedback Loop Reasoning at Lower Elementary Level

    ERIC Educational Resources Information Center

    Hokayem, Hayat; Ma, Jingjing; Jin, Hui

    2015-01-01

    This study examines to what extent elementary students use feedback loop reasoning, a key component of systems thinking, to reason about interactions among organisms in ecosystems. We conducted clinical interviews with 44 elementary students (1st through 4th grades). We asked students to explain how populations change in two contexts: a

  2. A Learning Progression for Feedback Loop Reasoning at Lower Elementary Level

    ERIC Educational Resources Information Center

    Hokayem, Hayat; Ma, Jingjing; Jin, Hui

    2015-01-01

    This study examines to what extent elementary students use feedback loop reasoning, a key component of systems thinking, to reason about interactions among organisms in ecosystems. We conducted clinical interviews with 44 elementary students (1st through 4th grades). We asked students to explain how populations change in two contexts: a…

  3. The BASL polarity protein controls a MAPK signaling feedback loop in asymmetric cell division.

    PubMed

    Zhang, Ying; Wang, Pengcheng; Shao, Wanchen; Zhu, Jian-Kang; Dong, Juan

    2015-04-20

    Cell polarization is linked to fate determination during asymmetric division of plant stem cells, but the underlying molecular mechanisms remain unknown. In Arabidopsis, BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL) is polarized to control stomatal asymmetric division. A mitogen-activated protein kinase (MAPK) cascade determines terminal stomatal fate by promoting the degradation of the lineage determinant SPEECHLESS (SPCH). Here, we demonstrate that a positive-feedback loop between BASL and the MAPK pathway constitutes a polarity module at the cortex. Cortical localization of BASL requires phosphorylation mediated by MPK3/6. Phosphorylated BASL functions as a scaffold and recruits the MAPKKK YODA and MPK3/6 to spatially concentrate signaling at the cortex. Activated MPK3/6 reinforces the feedback loop by phosphorylating BASL and inhibits stomatal fate by phosphorylating SPCH. Polarization of the BASL-MAPK signaling feedback module represents a mechanism connecting cell polarity to fate differentiation during asymmetric stem cell division in plants. PMID:25843888

  4. Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops.

    PubMed

    Mullins, Caitlin; Fishell, Gord; Tsien, Richard W

    2016-03-16

    Understanding the mechanisms underlying autism spectrum disorders (ASDs) is a challenging goal. Here we review recent progress on several fronts, including genetics, proteomics, biochemistry, and electrophysiology, that raise motivation for forming a viable pathophysiological hypothesis. In place of a traditionally unidirectional progression, we put forward a framework that extends homeostatic hypotheses by explicitly emphasizing autoregulatory feedback loops and known synaptic biology. The regulated biological feature can be neuronal electrical activity, the collective strength of synapses onto a dendritic branch, the local concentration of a signaling molecule, or the relative strengths of synaptic excitation and inhibition. The sensor of the biological variable (which we have termed the homeostat) engages mechanisms that operate as negative feedback elements to keep the biological variable tightly confined. We categorize known ASD-associated gene products according to their roles in such feedback loops and provide detailed commentary for exemplar genes within each module. PMID:26985722

  5. The BASL Polarity Protein Controls a MAPK Signaling Feedback Loop in Asymmetric Cell Division

    PubMed Central

    Zhang, Ying; Wang, Pengcheng; Shao, Wanchen; Zhu, Jian-Kang; Dong, Juan

    2015-01-01

    SUMMARY Cell polarization is linked to fate determination during asymmetric division of plant stem cells, but the underlying molecular mechanisms remain unknown. In Arabidopsis, BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL) is polarized to control stomatal asymmetric division. A MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) cascade determines terminal stomatal fate by promoting the degradation of the lineage determinant SPEECHLESS (SPCH). Here we demonstrate that a positive feedback loop between BASL and the MAPK pathway constitutes a polarity module at the cortex. Cortical localization of BASL requires phosphorylation mediated by MPK3/6. Phosphorylated BASL functions as a scaffold and recruits the MAPKKK YODA and MPK3/6 to spatially concentrate signaling at the cortex. Activated MPK3/6 reinforces the feedback loop by phosphorylating BASL, and inhibits stomatal fate by phosphorylating SPCH. Polarization of the BASL-MAPK signaling feedback module represents a mechanism connecting cell polarity to fate differentiation during asymmetric stem cell division in plants. PMID:25843888

  6. Closing the sensorimotor loop: haptic feedback facilitates decoding of motor imagery

    NASA Astrophysics Data System (ADS)

    Gomez-Rodriguez, M.; Peters, J.; Hill, J.; Schölkopf, B.; Gharabaghi, A.; Grosse-Wentrup, M.

    2011-06-01

    The combination of brain-computer interfaces (BCIs) with robot-assisted physical therapy constitutes a promising approach to neurorehabilitation of patients with severe hemiparetic syndromes caused by cerebrovascular brain damage (e.g. stroke) and other neurological conditions. In such a scenario, a key aspect is how to reestablish the disrupted sensorimotor feedback loop. However, to date it is an open question how artificially closing the sensorimotor feedback loop influences the decoding performance of a BCI. In this paper, we answer this issue by studying six healthy subjects and two stroke patients. We present empirical evidence that haptic feedback, provided by a seven degrees of freedom robotic arm, facilitates online decoding of arm movement intention. The results support the feasibility of future rehabilitative treatments based on the combination of robot-assisted physical therapy with BCIs.

  7. Tracking algorithm for the gain of the phase modulator in closed-loop optical voltage sensors

    NASA Astrophysics Data System (ADS)

    Hui, Li; Lan, Bi; Lijing, Li; Shuling, Hu; Xiujuan, Feng; Chunxi, Zhang

    2013-04-01

    The accuracy and scale factor of the optical voltage sensor are considerably affected by the gain drift of the phase modulator induced by temperature fluctuation. In this paper, we present a tracking system for the gain drift of the phase modulator based on four-state modulation which provides a significant improvement in the performance of the optical voltage sensor. We analyze the influence of the main closed-loop error of optical voltage sensor on the tracking system. The analysis results indicate that the main closed-loop error causes uncertain parameter and external disturbance for the tracking system. Then the model of the tracking system for the gain of the phase modulator is transformed into a dynamic system with uncertainty and stochastic disturbance by substitution of variable. The tracking system is accurately designed considering the main closed-loop error. To insure the tracking system achieves good transient performance, the closed-loop poles of the tracking system are constrained to locate in a desired circular region, while the gain error is mean-square exponentially stable via the robust control. The experiments show that the tracking system realizes precise compensation for the gain drift of the phase modulator.

  8. Numerical analysis of tonal airfoil self-noise and acoustic feedback-loops

    NASA Astrophysics Data System (ADS)

    Jones, Lloyd E.; Sandberg, Richard D.

    2011-12-01

    In this study the role of acoustic feedback instabilities in the tonal airfoil self-noise phenomenon is investigated. First, direct numerical simulations are conducted of the flow around a NACA-0012 airfoil at Re=1×105 and four angles of attack. At the two lowest angles of attack considered the airfoil self-noise exhibits a clear tonal contribution, whereas at the two higher angles of attack the tonal contribution becomes less significant in comparison to the broadband noise. Classical linear stability analysis of time-averaged boundary layer profiles shows that the tonal noise occurs at a frequency significantly lower than that of the most convectively amplified instability wave. Two-dimensional linear stability analysis of the time-averaged flowfield is then performed, illustrating the presence of an acoustic feedback loop involving the airfoil trailing edge. The feedback loop is found to be unstable only for the cases where tonal self-noise is prominent, and is found to self-select a frequency almost identical to that of the tonal self-noise. The constituent mechanisms of the acoustic feedback loop are considered, which appear to explain why the preferred frequency is lower than that of the most convectively amplified instability wave.

  9. Stabilization of Gyrotron Frequency by PID Feedback Control on the Acceleration Voltage

    NASA Astrophysics Data System (ADS)

    Khutoryan, E. M.; Idehara, T.; Kuleshov, A. N.; Tatematsu, Y.; Yamaguchi, Y.; Matsuki, Y.; Fujiwara, T.

    2015-12-01

    The results of frequency stabilization by proportional-integral-derivative (PID) feedback control of acceleration voltage in the 460-GHz Gyrotron FU CW GVI (the official name in Osaka University is Gyrotron FU CW GOI) are presented. The experiment was organized on the basis of the frequency modulation by modulation of acceleration voltage of beam electrons. The frequency stabilization during 10 h experiment was better than 10-6, which is compared with the results of the frequency deviation in free-running gyrotron operation.

  10. Gyrotron Output Power Stabilization by PID Feedback Control of Heater Current and Anode Voltage

    NASA Astrophysics Data System (ADS)

    Khutoryan, E. M.; Idehara, T.; Kuleshov, A. N.; Ueda, K.

    2014-12-01

    To provide stable output power of a gyrotron during long operation time the power stabilization was achieved by two schemes with PID feedback control of heater current and anode voltage. It was based on the dependence of the output power on both the anode voltage and the beam current and also on the dependence of the beam current on the gun heater current. Both schemes provided decrease of the power standard deviation to 0.3-0.5%. The comparison between parameters of both schemes is discussed in the paper.

  11. A transient-enhanced NMOS low dropout voltage regulator with parallel feedback compensation

    NASA Astrophysics Data System (ADS)

    Han, Wang; Lin, Tan

    2016-02-01

    This paper presents a transient-enhanced NMOS low-dropout regulator (LDO) for portable applications with parallel feedback compensation. The parallel feedback structure adds a dynamic zero to get an adequate phase margin with a load current variation from 0 to 1 A. A class-AB error amplifier and a fast charging/discharging unit are adopted to enhance the transient performance. The proposed LDO has been implemented in a 0.35 μm BCD process. From experimental results, the regulator can operate with a minimum dropout voltage of 150 mV at a maximum 1 A load and IQ of 165 μA. Under the full range load current step, the voltage undershoot and overshoot of the proposed LDO are reduced to 38 mV and 27 mV respectively.

  12. Sensory feedback in prosthetics: a standardized test bench for closed-loop control.

    PubMed

    Dosen, Strahinja; Markovic, Marko; Hartmann, Cornelia; Farina, Dario

    2015-03-01

    Closing the control loop by providing sensory feedback to the user of a prosthesis is an important challenge, with major impact on the future of prosthetics. Developing and comparing closed-loop systems is a difficult task, since there are many different methods and technologies that can be used to implement each component of the system. Here, we present a test bench developed in Matlab Simulink for configuring and testing the closed-loop human control system in standardized settings. The framework comprises a set of connected generic blocks with normalized inputs and outputs, which can be customized by selecting specific implementations from a library of predefined components. The framework is modular and extensible and it can be used to configure, compare and test different closed-loop system prototypes, thereby guiding the development towards an optimal system configuration. The use of the test bench was demonstrated by investigating two important aspects of closed-loop control: performance of different electrotactile feedback interfaces (spatial versus intensity coding) during a pendulum stabilization task and feedforward methods (joystick versus myocontrol) for force control. The first experiment demonstrated that in the case of trained subjects the intensity coding might be superior to spatial coding. In the second experiment, the control of force was rather poor even with a stable and precise control interface (joystick), demonstrating that inherent characteristics of the prosthesis can be an important limiting factor when considering the overall effectiveness of the closed-loop control. The presented test bench is an important instrument for investigating different aspects of human manual control with sensory feedback. PMID:25420268

  13. Negative Feedback Loops Involving Small Regulatory RNAs Precisely Control the Vibrio harveyi Quorum-Sensing Response

    PubMed Central

    Tu, Kimberly C.; Long, Tao; Svenningsen, Sine L.; Wingreen, Ned S.; Bassler, Bonnie L.

    2010-01-01

    Summary Quorum sensing (QS) bacteria assess population density through secretion and detection of molecules called autoinducers (AIs). We identify and characterize two Vibrio harveyi negative feedback loops that facilitate precise transitions between low-cell-density (LCD) and high-cell-density (HCD) states. The QS central regulator LuxO autorepresses its own transcription and the Qrr small regulatory RNAs (sRNAs) posttranscriptionally repress luxO. Disrupting feedback increases the concentration of AIs required for cells to transit from LCD to HCD QS modes. Thus, the two cooperative negative feedback loops determine the point at which V. harveyi has reached a quorum and control the range of AIs over which the transition occurs. Negative feedback regulation also constrains the range of QS output – by preventing sRNA levels from becoming too high and preventing luxO mRNA levels from reaching zero. We suggest that sRNA-mediated feedback regulation is a network design feature that permits fine-tuning of gene regulation and maintenance of homeostasis. PMID:20188674

  14. Stochastic analysis of bistability in coherent mixed feedback loops combining transcriptional and posttranscriptional regulations

    NASA Astrophysics Data System (ADS)

    Nitzan, Mor; Shimoni, Yishai; Rosolio, Oded; Margalit, Hanah; Biham, Ofer

    2015-05-01

    Mixed feedback loops combining transcriptional and posttranscriptional regulations are common in cellular regulatory networks. They consist of two genes, encoding a transcription factor and a small noncoding RNA (sRNA), which mutually regulate each other's expression. We present a theoretical and numerical study of coherent mixed feedback loops of this type, in which both regulations are negative. Under suitable conditions, these feedback loops are expected to exhibit bistability, namely, two stable states, one dominated by the transcriptional repressor and the other dominated by the sRNA. We use deterministic methods based on rate equation models, in order to identify the range of parameters in which bistability takes place. However, the deterministic models do not account for the finite lifetimes of the bistable states and the spontaneous, fluctuation-driven transitions between them. Therefore, we use stochastic methods to calculate the average lifetimes of the two states. It is found that these lifetimes strongly depend on rate coefficients such as the transcription rates of the transcriptional repressor and the sRNA. In particular, we show that the fraction of time the system spends in the sRNA-dominated state follows a monotonically decreasing sigmoid function of the transcriptional repressor transcription rate. The biological relevance of these results is discussed in the context of such mixed feedback loops in Escherichia coli. It is shown that the fluctuation-driven transitions and the dependence of some rate coefficients on the biological conditions enable the cells to switch to the state which is better suited for the existing conditions and to remain in that state as long as these conditions persist.

  15. A social feedback loop for speech development and its reduction in autism

    PubMed Central

    Warlaumont, Anne S.; Richards, Jeffrey A.; Gilkerson, Jill; Oller, D. Kimbrough

    2014-01-01

    We analyze the microstructure of child-adult interaction during naturalistic, daylong, automatically labeled audio recordings (13,836 hours total) of children (8- to 48-month-olds) with and without autism. We find that adult responses are more likely when child vocalizations are speech-related. In turn, a child vocalization is more likely to be speech-related if the previous speech-related child vocalization received an immediate adult response. Taken together, these results are consistent with the idea that there is a social feedback loop between child and caregiver that promotes speech-language development. Although this feedback loop applies in both typical development and autism, children with autism produce proportionally fewer speech-related vocalizations and the responses they receive are less contingent on whether their vocalizations are speech-related. We argue that such differences will diminish the strength of the social feedback loop with cascading effects on speech development over time. Differences related to socioeconomic status are also reported. PMID:24840717

  16. A model for improving microbial biofuel production using a synthetic feedback loop

    SciTech Connect

    Dunlop, Mary; Keasling, Jay; Mukhopadhyay, Aindrila

    2011-07-14

    Cells use feedback to implement a diverse range of regulatory functions. Building synthetic feedback control systems may yield insight into the roles that feedback can play in regulation since it can be introduced independently of native regulation, and alternative control architectures can be compared. We propose a model for microbial biofuel production where a synthetic control system is used to increase cell viability and biofuel yields. Although microbes can be engineered to produce biofuels, the fuels are often toxic to cell growth, creating a negative feedback loop that limits biofuel production. These toxic effects may be mitigated by expressing efflux pumps that export biofuel from the cell. We developed a model for cell growth and biofuel production and used it to compare several genetic control strategies for their ability to improve biofuel yields. We show that controlling efflux pump expression directly with a biofuel-responsive promoter is a straight forward way of improving biofuel production. In addition, a feed forward loop controller is shown to be versatile at dealing with uncertainty in biofuel production rates.

  17. Ultra-high-frequency piecewise-linear chaos using delayed feedback loops.

    PubMed

    Cohen, Seth D; Rontani, Damien; Gauthier, Daniel J

    2012-12-01

    We report on an ultra-high-frequency (>1 GHz), piecewise-linear chaotic system designed from low-cost, commercially available electronic components. The system is composed of two electronic time-delayed feedback loops: A primary analog loop with a variable gain that produces multi-mode oscillations centered around 2 GHz and a secondary loop that switches the variable gain between two different values by means of a digital-like signal. We demonstrate experimentally and numerically that such an approach allows for the simultaneous generation of analog and digital chaos, where the digital chaos can be used to partition the system's attractor, forming the foundation for a symbolic dynamics with potential applications in noise-resilient communications and radar. PMID:23278047

  18. Regulation of release factor expression using a translational negative feedback loop: A systems analysis

    PubMed Central

    Betney, Russell; de Silva, Eric; Mertens, Christina; Knox, Yvonne; Krishnan, J.; Stansfield, Ian

    2012-01-01

    The essential eukaryote release factor eRF1, encoded by the yeast SUP45 gene, recognizes stop codons during ribosomal translation. SUP45 nonsense alleles are, however, viable due to the establishment of feedback-regulated readthrough of the premature termination codon; reductions in full-length eRF1 promote tRNA-mediated stop codon readthrough, which, in turn, drives partial production of full-length eRF1. A deterministic mathematical model of this eRF1 feedback loop was developed using a staged increase in model complexity. Model predictions matched the experimental observation that strains carrying the mutant SUQ5 tRNA (a weak UAA suppressor) in combination with any of the tested sup45UAA nonsense alleles exhibit threefold more stop codon readthrough than that of an SUQ5 yeast strain. The model also successfully predicted that eRF1 feedback control in an SUQ5 sup45UAA mutant would resist, but not completely prevent, imposed changes in eRF1 expression. In these experiments, the introduction of a plasmid-borne SUQ5 copy into a sup45UAA SUQ5 mutant directed additional readthrough and full-length eRF1 expression, despite feedback. Secondly, induction of additional sup45UAA mRNA expression in a sup45UAA SUQ5 strain also directed increased full-length eRF1 expression. The autogenous sup45 control mechanism therefore acts not to precisely control eRF1 expression, but rather as a damping mechanism that only partially resists changes in release factor expression level. The validated model predicts that the degree of feedback damping (i.e., control precision) is proportional to eRF1 affinity for the premature stop codon. The validated model represents an important tool to analyze this and other translational negative feedback loops. PMID:23104998

  19. A computational model clarifies the roles of positive and negative feedback loops in the Drosophila circadian clock

    NASA Astrophysics Data System (ADS)

    Wang, Junwei; Zhou, Tianshou

    2010-06-01

    Previous studies showed that a single negative feedback structure should be sufficient for robust circadian oscillations. It is thus pertinent to ask why current cellular clock models almost universally have interlocked negative feedback loop (NFL) and positive feedback loop (PFL). Here, we propose a molecular model that reflects the essential features of the Drosophila circadian clock to clarify the different roles of negative and positive feedback loops. In agreement with experimental observations, the model can simulate circadian oscillations in constant darkness, entrainment by light-dark cycles, as well as phenotypes of per and clk mutants. Moreover, sustained oscillations persist when the PFL is removed, implying the crucial role of NFL for rhythm generation. Through parameter sensitivity analysis, it is revealed that incorporation of PFL increases the robustness of the system to regulatory processes in PFL itself. Such reduced models can aid understanding of the design principles of circadian clocks in Drosophila and other organisms with complex transcriptional feedback structures.

  20. Channel State Information Feedback with Zero-Overhead in Closed-Loop MIMO System

    NASA Astrophysics Data System (ADS)

    Zhang, Yiheng; Cui, Qimei; Zhang, Ping; Tao, Xiaofeng

    Dramatic gains in channel capacity can be achieved in the closed-loop MIMO system under the assumption that the base station (BS) can acquire the downlink channel state information (CSI) accurately. However, transmitting CSI with high precision is a heavy burden that wastes a lot of uplink bandwidth, while transmitting CSI within a limited bandwidth leads to the degradation of system performance. To address this problem, we propose a zero-overhead downlink CSI feedback scheme based on the hybrid pilot structure. The downlink CSI is contained in the hybrid pilots at mobile terminal (MT) side, fed back to BS via the uplink pilot channel, and recovered from hybrid pilot at BS side. Meanwhile the uplink channel is estimated based on the hybrid pilot at BS side. Since transmitting the hybrid pilots occupies the same bandwidth as transmitting traditional code division multiplexing based uplink pilots, no extra uplink channel bandwidth is occupied. Therefore, the overhead for downlink CSI feedback is zero. Moreover, the hybrid pilots are formed at MT side by superposing the received analog downlink pilots directly on the uplink pilots. Thus the downlink CSI estimation process is unnecessary at MT side, and MT's complexity can be reduced. Numerical Simulations prove that, the proposed downlink CSI feedback has the higher precision than the traditional feedback schemes while the overhead for downlink CSI feedback is zero.

  1. Closed-Loop Restoration Approach to Blurry Images Based on Machine Learning and Feedback Optimization.

    PubMed

    Yousaf, Saqib; Qin, Shiyin

    2015-12-01

    Blind image deconvolution (BID) aims to remove or reduce the degradations that have occurred during the acquisition or processing. It is a challenging ill-posed problem due to a lack of enough information in degraded image for unambiguous recovery of both point spread function (PSF) and clear image. Although recently many powerful algorithms appeared; however, it is still an active research area due to the diversity of degraded images as well as degradations. Closed-loop control systems are characterized with their powerful ability to stabilize the behavior response and overcome external disturbances by designing an effective feedback optimization. In this paper, we employed feedback control to enhance the stability of BID by driving the current estimation quality of PSF to the desired level without manually selecting restoration parameters and using an effective combination of machine learning with feedback optimization. The foremost challenge when designing a feedback structure is to construct or choose a suitable performance metric as a controlled index and a feedback information. Our proposed quality metric is based on the blur assessment of deconvolved patches to identify the best PSF and computing its relative quality. The Kalman filter-based extremum seeking approach is employed to find the optimum value of controlled variable. To find better restoration parameters, learning algorithms, such as multilayer perceptron and bagged decision trees, are used to estimate the generic PSF support size instead of trial and error methods. The problem is modeled as a combination of pattern classification and regression using multiple training features, including noise metrics, blur metrics, and low-level statistics. Multi-objective genetic algorithm is used to find key patches from multiple saliency maps which enhance performance and save extra computation by avoiding ineffectual regions of the image. The proposed scheme is shown to outperform corresponding open-loop schemes, which often fails or needs many assumptions regarding images and thus resulting in sub-optimal results. PMID:26513786

  2. The self-regulated AGN feedback loop: the role of chaotic cold accretion

    NASA Astrophysics Data System (ADS)

    Gaspari, Massimo

    2015-08-01

    Accretion and feedback tied to supermassive black holes are known to play central role in the cosmic evolution of galaxies, groups, and clusters of galaxies. The self-regulation mechanism, that is how to link feedback and accretion, is matter of intense debate.Using high-resolution 3D hydrodynamic simulations, I discuss how the AGN feedback is tightly coupled with the formation of multiphase gas and the newly probed chaotic cold accretion. In a turbulent atmosphere heated by AGN feedback, cold clouds and filaments condense out of the hot plasma via nonlinear thermal instability, up to radii of 10s kpc, and rain toward the black hole. In the inner core, the recurrent chaotic collisions between the cold clouds, filaments, and central torus promote angular momentum cancellation, boosting the accretion rate up to 100 times the Bondi rate, which is comparable to the cooling rate.Such rapid variability triggers powerful AGN outflows, which quench the cooling flow and star formation without destroying the cool core. I highlight the major imprints of mechanical AGN feedback, such as buoyant bubbles, shocks, turbulence, and uplifted gas, with a critical eye toward concordance with X-ray observations. The tight self-regulation has key implications for the group/cluster scaling relations, such as Lx-Tx, in agreement with a recent X-ray stacking analysis of 250000 central galaxies.The AGN heating stifles the formation of multiphase gas, and thus accretion. Lacking the main fuel, AGN feedback subsides and the hot halo is allowed to cool again, restarting a new cycle. Ultimately, chaotic cold accretion creates a symbiotic link between the black hole and the whole host galaxy, leading to a tight self-regulated feedback loop which preserves the cores of groups and clusters in quasi thermal equilibrium throughout cosmic time.

  3. The self-regulated AGN feedback loop: the role of chaotic cold accretion

    NASA Astrophysics Data System (ADS)

    Gaspari, Massimo

    2015-08-01

    Accretion and feedback tied to supermassive black holes are known to play central role in the cosmic evolution of galaxies, groups, and clusters of galaxies. The self-regulation mechanism, that is how to link feedback and accretion, is matter of intense debate.Using high-resolution 3D hydrodynamic simulations, I discuss how the AGN feedback is tightly coupled with the formation of multiphase gas and the newly probed chaotic cold accretion. In a turbulent atmosphere heated by AGN feedback, cold clouds and filaments condense out of the hot plasma via nonlinear thermal instability, up to radii of 10s kpc, and rain toward the black hole. In the inner core, the recurrent chaotic collisions between the cold clouds, filaments, and central torus promote angular momentum cancellation, boosting the accretion rate up to 100 times the Bondi rate, which is comparable to the cooling rate.Such rapid variability triggers powerful AGN outflows, which quench the cooling flow and star formation without destroying the cool core. I highlight the major imprints of mechanical AGN feedback, such as buoyant bubbles, shocks, turbulence, and uplifted gas, with a critical eye toward observational concordance. The tight self-regulation has key implications for the scaling relations, such as Lx-Tx, and the X-ray spectrum of hot halos.The AGN heating stifles the formation of multiphase gas, and thus accretion. Lacking the main fuel, AGN feedback subsides and the hot halo is allowed to cool again, restarting a new cycle. Ultimately, chaotic cold accretion creates a symbiotic link between the black hole and the whole host galaxy, leading to a tight self-regulated feedback loop which preserves the cores of groups and clusters in quasi thermal equilibrium throughout cosmic time.

  4. The self-regulated AGN feedback loop: the role of chaotic cold accretion

    NASA Astrophysics Data System (ADS)

    Gaspari, Massimo

    2015-08-01

    Accretion and feedback tied to supermassive black holes are known to play central role in the cosmic evolution of galaxies, groups, and clusters of galaxies. The self-regulation mechanism, that is how to link feedback and accretion, is matter of intense debate.Using high-resolution 3D hydrodynamic simulations, I discuss how the AGN feedback is tightly coupled with the formation of multiphase gas and the newly probed chaotic cold accretion. In a turbulent atmosphere heated by AGN feedback, cold clouds and filaments condense out of the hot plasma via nonlinear thermal instability, up to radii of 10s kpc, and rain toward the black hole. In the inner core, the recurrent chaotic collisions between the cold clouds, filaments, and central torus promote angular momentum cancellation, boosting the accretion rate up to 100 times the Bondi rate, which is comparable to the cooling rate.Such rapid variability triggers powerful AGN outflows, which quench the cooling flow and star formation without destroying the cool core. I highlight the major imprints of mechanical AGN feedback, such as buoyant bubbles, shocks, turbulence, and uplifted gas, with a critical eye toward observational concordance. The tight self-regulation has key implications for the group/cluster scaling relations, such as Lx-Tx, in agreement with a recent X-ray stacking analysis of 250000 central galaxies.The AGN heating stifles the formation of multiphase gas, and thus accretion. Lacking the main fuel, AGN feedback subsides and the hot halo is allowed to cool again, restarting a new cycle. Ultimately, chaotic cold accretion creates a symbiotic link between the black hole and the whole host galaxy, leading to a tight self-regulated feedback loop which preserves the cores of groups and clusters in quasi thermal equilibrium throughout cosmic time.

  5. Optical frequency stabilization in infrared region using improved dual feed-back loop

    NASA Astrophysics Data System (ADS)

    Ružička, B.; Číp, O.; Lazar, J.

    2007-03-01

    Modern technologies such as DWDM (Dense Wavelength Division Multiplex) need precise stability of laser frequencies. According to this fact, requirements of new etalons of optical frequencies in the telecommunication band is rapidly growing. Lasers working in near infrared telecommunication band (1500-1600 nm) can be stabilized to 12C IIH II or 13C IIH II (acetylene) gas absorption lines. The acetylene gas absorption has been widely studied and accepted by international bodies of standardization as a primary wavelength reference in the near infrared band around 1550 nm. Our aim was to design and develop a compact fibre optics laser system generating coherent light in near-IR band with high frequency stability (at least 1.10 -8). This system should become a base for realization of a primary frequency standard for optical communications in the Czech Republic. Such an etalon will be needed for calibration of wavelengthmeters and spectral analysers for DWDM communication systems. We are co-operating with CMI (Czech Metrology Institute) on this project. We present stabilized laser system based on a single frequency DFB (Distributed Feedback) laser diode with a narrow spectral profile. The laser is pre-stabilized by means of the FM-spectroscopy on a passive resonator. Thanks to a fast feed-back loop we are able to improve spectral characteristics of the laser. The laser frequency is locked by a relatively slow second feed-back loop on an absorption line of acetylene vapour which is sealed in a cell under the optimised pressure.

  6. Functional characteristics of a double positive feedback loop coupled with autorepression

    NASA Astrophysics Data System (ADS)

    Banerjee, Subhasis; Bose, Indrani

    2008-12-01

    We study the functional characteristics of a two-gene motif consisting of a double positive feedback loop and an autoregulatory negative feedback loop. The motif appears in the gene regulatory network controlling the functional activity of pancreatic β-cells. The model exhibits bistability and hysteresis in appropriate parameter regions. The two stable steady states correspond to low (OFF state) and high (ON state) protein levels, respectively. Using a deterministic approach, we show that the region of bistability increases in extent when the copy number of one of the genes is reduced from 2 to 1. The negative feedback loop has the effect of reducing the size of the bistable region. Loss of a gene copy, brought about by mutations, hampers the normal functioning of the β-cells giving rise to the genetic disorder, maturity-onset diabetes of the young (MODY). The diabetic phenotype makes its appearance when a sizable fraction of the β-cells is in the OFF state. Using stochastic simulation techniques we show that, on reduction of the gene copy number, there is a transition from the monostable ON to the ON state in the bistable region of the parameter space. Fluctuations in the protein levels, arising due to the stochastic nature of gene expression, can give rise to transitions between the ON and OFF states. We show that as the strength of autorepression increases, the ON → OFF state transitions become less probable whereas the reverse transitions are more probable. The implications of the results in the context of the occurrence of MODY are pointed out.

  7. Dynamics and feedback loops in the transforming growth factor ? signaling pathway.

    PubMed

    Wegner, Katja; Bachmann, Anastasia; Schad, Jan-Ulrich; Lucarelli, Philippe; Sahle, Sven; Nickel, Peter; Meyer, Christoph; Klingmller, Ursula; Dooley, Steven; Kummer, Ursula

    2012-03-01

    Transforming growth factor ? (TGF-?) ligands activate a signaling cascade with multiple cell context dependent outcomes. Disruption or disturbance leads to variant clinical disorders. To develop strategies for disease intervention, delineation of the pathway in further detail is required. Current theoretical models of this pathway describe production and degradation of signal mediating proteins and signal transduction from the cell surface into the nucleus, whereas feedback loops have not exhaustively been included. In this study we present a mathematical model to determine the relevance of feedback regulators (Arkadia, Smad7, Smurf1, Smurf2, SnoN and Ski) on TGF-? target gene expression and the potential to initiate stable oscillations within a realistic parameter space. We employed massive sampling of the parameters space to pinpoint crucial players for potential oscillations as well as transcriptional product levels. We identified Smad7 and Smurf2 with the highest impact on the dynamics. Based on these findings, we conducted preliminary time course experiments. PMID:22284904

  8. Dicer and Hsp104 function in a negative feedback loop to confer robustness to environmental stress.

    PubMed

    Oberti, Daniele; Biasini, Adriano; Kirschmann, Moritz Alexander; Genoud, Christel; Stunnenberg, Rieka; Shimada, Yukiko; Bhler, Marc

    2015-01-01

    Epigenetic mechanisms can be influenced by environmental cues and thus evoke phenotypic variation. This plasticity can be advantageous for adaptation but also detrimental if not tightly controlled. Although having attracted considerable interest, it remains largely unknown if and how environmental cues such as temperature trigger epigenetic alterations. Using fission yeast, we demonstrate that environmentally induced discontinuous phenotypic variation is buffered by a negative feedback loop that involves the RNase Dicer and the protein disaggregase Hsp104. In the absence of Hsp104, Dicer accumulates in cytoplasmic inclusions and heterochromatin becomes unstable at elevated temperatures, an epigenetic state inherited for many cell divisions after the heat stress. Loss of Dicer leads to toxic aggregation of an exogenous prionogenic protein. Our results highlight the importance of feedback regulation in building epigenetic memory and uncover Hsp104 and Dicer as homeostatic controllers that buffer environmentally induced stochastic epigenetic variation and toxic aggregation of prionogenic proteins. PMID:25543137

  9. Pyruvate kinase triggers a metabolic feedback loop that controls redox metabolism in respiring cells.

    PubMed

    Grüning, Nana-Maria; Rinnerthaler, Mark; Bluemlein, Katharina; Mülleder, Michael; Wamelink, Mirjam M C; Lehrach, Hans; Jakobs, Cornelis; Breitenbach, Michael; Ralser, Markus

    2011-09-01

    In proliferating cells, a transition from aerobic to anaerobic metabolism is known as the Warburg effect, whose reversal inhibits cancer cell proliferation. Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism when respiration is activated. Low PYK activity activated yeast respiration. However, levels of reactive oxygen species (ROS) did not increase, and cells gained resistance to oxidants. This adaptation was attributable to accumulation of the PYK substrate phosphoenolpyruvate (PEP). PEP acted as feedback inhibitor of the glycolytic enzyme triosephosphate isomerase (TPI). TPI inhibition stimulated the pentose phosphate pathway, increased antioxidative metabolism, and prevented ROS accumulation. Thus, a metabolic feedback loop, initiated by PYK, mediated by its substrate and acting on TPI, stimulates redox metabolism in respiring cells. Originating from a single catalytic step, this autonomous reconfiguration of central carbon metabolism prevents oxidative stress upon shifts between fermentation and respiration. PMID:21907146

  10. A closed loop feedback system for automatic detection and inhibition of mechano-nociceptive neural activity.

    PubMed

    Farajidavar, Aydin; Hagains, Christopher E; Peng, Yuan B; Chiao, J-C

    2012-07-01

    Clinical studies have shown that spinal or cerebral neurostimulation can significantly relieve pain. Current neurostimulators work in an open loop; hence, their efficacy depends on the patient's or physician's comprehension of pain. We have proposed and developed a real-time automatic recognition program with signal processing functions to detect action potentials. By using a wireless neurorecording module, spinal neuronal responses to mechanical stimuli (brush, pressure, and pinch) applied to rats' hind paws were recorded. Nociceptive spinal responses were detected and suppressed by our automated module through delivering electrical stimulation to the periaqueductal gray (PAG). The interspike intervals (ISIs) of the fired action potentials were used to distinguish among the three different mechanical stimuli. Our system was able to detect the neuronal activity intensities and deliver trigger signals to the neurostimulator according to a pre-set threshold in a closed-loop feedback configuration, thereby suppressing excessive activity in spinal cord dorsal horn neurons. PMID:22692935

  11. Androgynous, Reconfigurable Closed Loop Feedback Controlled Low Impact Docking System With Load Sensing Electromagnetic Capture Ring

    NASA Technical Reports Server (NTRS)

    Lewis, James L. (Inventor); Carroll, Monty B. (Inventor); Morales, Ray H. (Inventor); Le, Thang D. (Inventor)

    2002-01-01

    The present invention relates to a fully androgynous, reconfigurable closed loop feedback controlled low impact docking system with load sensing electromagnetic capture ring. The docking system of the present invention preferably comprises two Docking- assemblies, each docking assembly comprising a load sensing ring having an outer face, one of more electromagnets, one or more load cells coupled to said load sensing ring. The docking assembly further comprises a plurality of actuator arms coupled to said load sensing ring and capable of dynamically adjusting the orientation of said load sensing ring and a reconfigurable closed loop control system capable of analyzing signals originating from said plurality of load cells and of outputting real time control for each of the actuators. The docking assembly of the present invention incorporates an active load sensing system to automatically dynamically adjust the load sensing ring during capture instead of requiring significant force to push and realign the ring.

  12. Synthetic Feedback Loop Model for Increasing Microbial Biofuel Production Using a Biosensor

    PubMed Central

    Harrison, Mary E.; Dunlop, Mary J.

    2012-01-01

    Current biofuel production methods use engineered bacteria to break down cellulose and convert it to biofuel. A major challenge in microbial fuel production is that increasing biofuel yields can be limited by the toxicity of the biofuel to the organism that is producing it. Previous research has demonstrated that efflux pumps are effective at increasing tolerance to various biofuels. However, when overexpressed, efflux pumps burden cells, which hinders growth and slows biofuel production. Therefore, the toxicity of the biofuel must be balanced with the toxicity of pump overexpression. We have developed a mathematical model for cell growth and biofuel production that implements a synthetic feedback loop using a biosensor to control efflux pump expression. In this way, the production rate will be maximal when the concentration of biofuel is low because the cell does not expend energy expressing efflux pumps when they are not needed. Additionally, the microbe is able to adapt to toxic conditions by triggering the expression of efflux pumps, which allow it to continue biofuel production. Sensitivity analysis indicates that the feedback sensor model is insensitive to many system parameters, but a few key parameters can influence growth and production. In comparison to systems that express efflux pumps at a constant level, the feedback sensor increases overall biofuel production by delaying pump expression until it is needed. This result is more pronounced when model parameters are variable because the system can use feedback to adjust to the actual rate of biofuel production. PMID:23112794

  13. Development of the Mayo Investigational Neuromodulation Control System: toward a closed-loop electrochemical feedback system for deep brain stimulation

    PubMed Central

    Chang, Su-Youne; Kimble, Christopher J.; Kim, Inyong; Paek, Seungleal B.; Kressin, Kenneth R.; Boesche, Joshua B.; Whitlock, Sidney V.; Eaker, Diane R.; Kasasbeh, Aimen; Horne, April E.; Blaha, Charles D.; Bennet, Kevin E.; Lee, Kendall H.

    2014-01-01

    Object Conventional deep brain stimulation (DBS) devices continue to rely on an open-loop system in which stimulation is independent of functional neural feedback. The authors previously proposed that as the foundation of a DBS “smart” device, a closed-loop system based on neurochemical feedback, may have the potential to improve therapeutic outcomes. Alterations in neurochemical release are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic voltammetry (FSCV) has been shown to be effective for recording these evoked neurochemical changes. However, the combination of FSCV with conventional DBS devices interferes with the recording and identification of the evoked analytes. To integrate neurochemical recording with neurostimulation, the authors developed the Mayo Investigational Neuromodulation Control System (MINCS), a novel, wirelessly controlled stimulation device designed to interface with FSCV performed by their previously described Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS). Methods To test the functionality of these integrated devices, various frequencies of electrical stimulation were applied by MINCS to the medial forebrain bundle of the anesthetized rat, and striatal dopamine release was recorded by WINCS. The parameters for FSCV in the present study consisted of a pyramidal voltage waveform applied to the carbon-fiber microelectrode every 100 msec, ramping between −0.4 V and +1.5 V with respect to an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec. The carbon-fiber microelectrode was held at the baseline potential of −0.4 V between scans. Results By using MINCS in conjunction with WINCS coordinated through an optic fiber, the authors interleaved intervals of electrical stimulation with FSCV scans and thus obtained artifact-free wireless FSCV recordings. Electrical stimulation of the medial forebrain bundle in the anesthetized rat by MINCS elicited striatal dopamine release that was time-locked to stimulation and increased progressively with stimulation frequency. Conclusions Here, the authors report a series of proof-of-principle tests in the rat brain demonstrating MINCS to be a reliable and flexible stimulation device that, when used in conjunction with WINCS, performs wirelessly controlled stimulation concurrent with artifact-free neurochemical recording. These findings suggest that the integration of neurochemical recording with neurostimulation may be a useful first step toward the development of a closed-loop DBS system for human application. PMID:24116724

  14. Linear state feedback, quadratic weights, and closed loop eigenstructures. M.S. Thesis. Final Report

    NASA Technical Reports Server (NTRS)

    Thompson, P. M.

    1980-01-01

    Equations are derived for the angles of general multivariable root loci and linear quadratic optimal root loci, including angles of departure and approach. The generalized eigenvalue problem is used to compute angles of approach. Equations are also derived to find the sensitivity of closed loop eigenvalue and the directional derivatives of closed loop eigenvectors. An equivalence class of quadratic weights that produce the same asymptotic eigenstructure is defined, a canonical element is defined, and an algorithm to find it is given. The behavior of the optimal root locus in the nonasymptotic region is shown to be different for quadratic weights with the same asymptotic properties. An algorithm is presented that can be used to select a feedback gain matrix for the linear state feedback problem which produces a specified asymptotic eigenstructure. Another algorithm is given to compute the asymptotic eigenstructure properties inherent in a given set of quadratic weights. Finally, it is shown that optimal root loci for nongeneric problems can be approximated by generic ones in the nonasymptotic region.

  15. Closed-Loop Control of Myoelectric Prostheses With Electrotactile Feedback: Influence of Stimulation Artifact and Blanking.

    PubMed

    Hartmann, Cornelia; Dosen, Strahinja; Amsuess, Sebastian; Farina, Dario

    2015-09-01

    Electrocutaneous stimulation is a promising approach to provide sensory feedback to amputees, and thus close the loop in upper limb prosthetic systems. However, the stimulation introduces artifacts in the recorded electromyographic (EMG) signals, which may be detrimental for the control of myoelectric prostheses. In this study, artifact blanking with three data segmentation approaches was investigated as a simple method to restore the performance of pattern recognition in prosthesis control (eight motions) when EMG signals are corrupted by stimulation artifacts. The methods were tested over a range of stimulation conditions and using four feature sets, comprising both time and frequency domain features. The results demonstrated that when stimulation artifacts were present, the classification performance improved with blanking in all tested conditions. In some cases, the classification performance with blanking was at the level of the benchmark (artifact-free data). The greatest pulse duration and frequency that allowed a full performance recovery were 400 μs and 150 Hz, respectively. These results show that artifact blanking can be used as a practical solution to eliminate the negative influence of the stimulation artifact on EMG pattern classification in a broad range of conditions, thus allowing to close the loop in myoelectric prostheses using electrotactile feedback. PMID:25222951

  16. Better Bet-Hedging with coupled positive and negative feedback loops

    NASA Astrophysics Data System (ADS)

    Narula, Jatin; Igoshin, Oleg

    2011-03-01

    Bacteria use the phenotypic heterogeneity associated with bistable switches to distribute the risk of activating stress response strategies like sporulation and persistence. However bistable switches offer little control over the timing of phenotype switching and first passage times (FPT) for individual cells are found to be exponentially distributed. We show that a genetic circuit consisting of interlinked positive and negative feedback loops allows cells to control the timing of phenotypic switching. Using a mathematical model we find that in this system a stable high expression state and stable low expression limit cycle coexist and the FPT distribution for stochastic transitions between them shows multiple peaks at regular intervals. A multimodal FPT distribution allows cells to detect the persistence of stress and control the rate of phenotype transition of the population. We further show that extracellular signals from cell-cell communication that change the strength of the feedback loops can modulate the FPT distribution and allow cells even greater control in a bet-hedging strategy.

  17. PKCδ maintains phenotypes of tumor initiating cells through cytokine-mediated autocrine loop with positive feedback.

    PubMed

    Kim, R-K; Suh, Y; Hwang, E; Yoo, K-C; Choi, K-S; An, S; Hwang, S-G; Kim, I-G; Kim, M-J; Lee, H-J; Lee, S-J

    2015-11-12

    The existence of tumor initiating cells (TICs) has been emerged as a good therapeutic target for treatment of glioblastoma that is the most aggressive brain tumor with poor prognosis. However, the molecular mechanisms that regulate the phenotypes of TICs still remain obscure. In this study, we found that PKCδ, among PKC isoforms, is preferentially activated in TICs and acts as a critical regulator for the maintenance of TICs in glioblastoma. By modulating the expression levels or activity of PKCδ, we demonstrated that PKCδ promotes self-renewal and tumorigenic potentials of TICs. Importantly, we found that the activation of PKCδ persists in TICs through an autocrine loop with positive feedback that was driven by PKCδ/STAT3/IL-23/JAK signaling axis. Moreover, for phenotypes of TICs, we showed that PKCδ activates AKT signaling component by phosphorylation specifically on Ser473. Taken together, we proposed that TICs regulate their own population in glioblastoma through an autocrine loop with positive feedback that is driven by PKCδ-dependent secretion of cytokines. PMID:25746003

  18. Control of inertial acoustic cavitation in pulsed sonication using a real-time feedback loop system.

    PubMed

    Desjouy, Cyril; Poizat, Adrien; Gilles, Bruno; Inserra, Claude; Bera, Jean-Christophe

    2013-08-01

    Owing to the complex behavior of ultrasound-induced bubble clouds (nucleation, linear and nonlinear oscillations, collapse), acoustic cavitation remains a hardly controllable phenomenon, leading to poorly reproducible ultrasound-based therapies. A better control of the various aspects of cavitation phenomena for in vivo applications is a key requirement to improve emerging ultrasound therapies. Previous publications have reported on systems performing regulation of acoustic cavitation in continuous sonication when applied in vitro, but the main challenge today is to achieve real-time control of cavitation activity in pulsed sonication when used in vivo. The present work aims at developing a system to control acoustic cavitation in a pulsed wave condition using a real-time feedback loop. The experimental setup consists of a water bath in which is submerged a focused transducer (pulsed waves, frequency 550 kHz) used for sonication and a hydrophone used to listen to inertial cavitation. The designed regulation process allows the cavitation activity to be controlled through a 300 μs feedback loop. Without regulation, cavitation exhibits numerous bursts of intense activity and large variations of inertial cavitation level over time. In a regulated regime, the control of inertial cavitation activity within a pulse leads to consistent cavitation levels over time with an enhancement of the reproducibility. PMID:23927204

  19. Closing a quantum feedback loop for a superconducting qubit inside a cryostat

    NASA Astrophysics Data System (ADS)

    Andersen, Christian Kraglund; Kerckhoff, Joseph; Lehnert, Konrad W.; Chapman, Benjamin J.; Mølmer, Klaus

    Several quantum information protocols relies upon efficient feedback (or feed-forward) schemes. Recently, within the field of superconducting qubits, many experiments have shown tremendous progress towards high fidelity quantum feedback scheme. Some experiments work by traditional measurement based schemes where the classical output is processed on a classical ''computer'' before a signal is fed back to the qubits. Other approaches are working in a continuous coherent manner, where the full quantum description of the system creates an effective bath that relaxes the system into the desired state. This talk will present a different approach that aims to close a measurement based feedback loop inside a cryostat and, thus, the scheme works completely autonomous. This approach sidesteps many of the inefficiencies inherent in two-way communication between temperature stages in typical systems with room temperature controllers, and avoids increasing the cryogenic heat load. This controller may find a broad range of uses in multi-qubit systems, but here I analyze two specific demonstrative cases in single qubit-control and show simulations of the time evolution for the full system dynamics.

  20. Sub-millisecond closed-loop feedback stimulation between arbitrary sets of individual neurons

    PubMed Central

    Müller, Jan; Bakkum, Douglas J.; Hierlemann, Andreas

    2012-01-01

    We present a system to artificially correlate the spike timing between sets of arbitrary neurons that were interfaced to a complementary metal–oxide–semiconductor (CMOS) high-density microelectrode array (MEA). The system features a novel reprogrammable and flexible event engine unit to detect arbitrary spatio-temporal patterns of recorded action potentials and is capable of delivering sub-millisecond closed-loop feedback of electrical stimulation upon trigger events in real-time. The relative timing between action potentials of individual neurons as well as the temporal pattern among multiple neurons, or neuronal assemblies, is considered an important factor governing memory and learning in the brain. Artificially changing timings between arbitrary sets of spiking neurons with our system could provide a “knob” to tune information processing in the network. PMID:23335887

  1. Computer program for single input-output, single-loop feedback systems

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Additional work is reported on a completely automatic computer program for the design of single input/output, single loop feedback systems with parameter uncertainly, to satisfy time domain bounds on the system response to step commands and disturbances. The inputs to the program are basically the specified time-domain response bounds, the form of the constrained plant transfer function and the ranges of the uncertain parameters of the plant. The program output consists of the transfer functions of the two free compensation networks, in the form of the coefficients of the numerator and denominator polynomials, and the data on the prescribed bounds and the extremes actually obtained for the system response to commands and disturbances.

  2. Similarities and differences in the p53-mdm2 and NF-kB feedback loops

    NASA Astrophysics Data System (ADS)

    Krishna, Sandeep

    2008-03-01

    Ultradian oscillations in the p53 and NF-kB signalling systems are produced using similar mechanisms: a negative feedback loop combined with an effective time delay. However, seemingly small differences in the molecular implementation of this mechanism mean that the NF-kB system is in equilibrium in the resting state, while the p53 system is far from equilibrium. I will discuss how this affects the dynamical response of the systems. In particular, I will argue that the nonequilibrium driving makes the p53 system respond much faster to external stimuli than the NF-kB system. The interesting question then is whether this makes sense physiologically, and is consistent with the fact that p53 triggers cell-cycle arrest and apoptosis, while NF-kB triggers the immune response.

  3. Changes in Adolescents' Risk Factors Following Peer Sexual Coercion: Evidence for a Feedback Loop

    PubMed Central

    Young, Brennan J.; Furman, Wyndol; Jones, Meredith C.

    2012-01-01

    Investigators have identified a number of factors that increase the risk for experiencing sexual coercion, but as yet little is known about how sexual coercion in turn affects these risk factors. Using a sample of 110 adolescents, the current study examined the hypothesis that, after an incident of sexual coercion, adolescents would exhibit increases in several behaviors known to increase risk for victimization. As predicted, after experiencing sexual coercion, adolescents reported increased externalizing symptoms, more frequent sexual intercourse and a greater total number of intercourse partners. Finally, alcohol use, drug use, and problems related to substance use increased. These findings suggest the presence of a feedback loop, in which the experience of sexual coercion leads to an intensification of the factors that initially contributed risk for coercion. PMID:22559131

  4. Sub-millisecond closed-loop feedback stimulation between arbitrary sets of individual neurons.

    PubMed

    Müller, Jan; Bakkum, Douglas J; Hierlemann, Andreas

    2012-01-01

    We present a system to artificially correlate the spike timing between sets of arbitrary neurons that were interfaced to a complementary metal-oxide-semiconductor (CMOS) high-density microelectrode array (MEA). The system features a novel reprogrammable and flexible event engine unit to detect arbitrary spatio-temporal patterns of recorded action potentials and is capable of delivering sub-millisecond closed-loop feedback of electrical stimulation upon trigger events in real-time. The relative timing between action potentials of individual neurons as well as the temporal pattern among multiple neurons, or neuronal assemblies, is considered an important factor governing memory and learning in the brain. Artificially changing timings between arbitrary sets of spiking neurons with our system could provide a "knob" to tune information processing in the network. PMID:23335887

  5. A MALAT1/HIF-2α feedback loop contributes to arsenite carcinogenesis

    PubMed Central

    Xu, Yuan; Liu, Yi; Liu, Xinlu; Lu, Lu; Li, Jun; Wang, Qingling; Wei, Shaofeng; Shi, Le; Lu, Xiaolin; Liu, Qizhan; Zhang, Aihua

    2016-01-01

    Arsenic is well established as a human carcinogen, but the molecular mechanisms leading to arsenic-induced carcinogenesis are complex and elusive. It is also not known if lncRNAs are involved in arsenic-induced liver carcinogenesis. We have found that MALAT1, a non-coding RNA, is over-expressed in the sera of people exposed to arsenite and in hepatocellular carcinomas (HCCs), and MALAT1 has a close relation with the clinicopathological characteristics of HCC. In addition, hypoxia-inducible factor (HIF)-2α is up-regulated in HCCs, and MALAT1 and HIF-2α have a positive correlation in HCC tissues. During the malignant transformation of human hepatic epithelial (L-02) cells induced by a low concentration (2.0 μM) of arsenite, MALAT1 and HIF-2α are increased. In addition, arsenite-induced MALAT1 causes disassociation of the von Hippel-Lindau (VHL) protein from HIF-2α, therefore, alleviating VHL-mediated HIF-2α ubiquitination, which causes HIF-2α accumulation. In turn, HIF-2α transcriptionally regulates MALAT1, thus forming a positive feedback loop to ensure expression of arsenite-induced MALAT1 and HIF-2α, which are involved in malignant transformation. Moreover, MALAT1 and HIF-2α promote the invasive and metastatic capacities of arsenite-induced transformed L-02 cells and in HCC-LM3 cells. The capacities of MALAT1 and HIF-2α to promote tumor growth are validated in mouse xenograft models. In mice, arsenite induces an inflammatory response, and MALAT1 and HIF-2α are over-expressed. Together, these findings suggest that the MALAT1/HIF-2α feedback loop is involved in regulation of arsenite-induced malignant transformation. Our results not only confirm a novel mechanism involving reciprocal regulation between MALAT1 and HIF-2α, but also expand the understanding of the carcinogenic potential of arsenite. PMID:26735578

  6. A Novel DDB2-ATM Feedback Loop Regulates Human Cytomegalovirus Replication

    PubMed Central

    E, Xiaofei; Savidis, George; Chin, Christopher R.; Wang, Shixia; Lu, Shan; Brass, Abraham L.

    2014-01-01

    Human cytomegalovirus (HCMV) genome replication requires host DNA damage responses (DDRs) and raises the possibility that DNA repair pathways may influence viral replication. We report here that a nucleotide excision repair (NER)-associated-factor is required for efficient HCMV DNA replication. Mutations in genes encoding NER factors are associated with xeroderma pigmentosum (XP). One of the XP complementation groups, XPE, involves mutation in ddb2, which encodes DNA damage binding protein 2 (DDB2). Infectious progeny virus production was reduced by >2 logs in XPE fibroblasts compared to levels in normal fibroblasts. The levels of immediate early (IE) (IE2), early (E) (pp65), and early/late (E/L) (gB55) proteins were decreased in XPE cells. These replication defects were rescued by infection with a retrovirus expressing DDB2 cDNA. Similar patterns of reduced viral gene expression and progeny virus production were also observed in normal fibroblasts that were depleted for DDB2 by RNA interference (RNAi). Mature replication compartments (RCs) were nearly absent in XPE cells, and there were 1.5- to 2.0-log reductions in viral DNA loads in infected XPE cells relative to those in normal fibroblasts. The expression of viral genes (UL122, UL44, UL54, UL55, and UL84) affected by DDB2 status was also sensitive to a viral DNA replication inhibitor, phosphonoacetic acid (PAA), suggesting that DDB2 affects gene expression upstream of or events associated with the initiation of DNA replication. Finally, a novel, infection-associated feedback loop between DDB2 and ataxia telangiectasia mutated (ATM) was observed in infected cells. Together, these results demonstrate that DDB2 and a DDB2-ATM feedback loop influence HCMV replication. PMID:24335308

  7. Feedback loops and temporal misalignment in component-based hydrologic modeling

    NASA Astrophysics Data System (ADS)

    Elag, Mostafa M.; Goodall, Jonathan L.; Castronova, Anthony M.

    2011-12-01

    In component-based modeling, a complex system is represented as a series of loosely integrated components with defined interfaces and data exchanges that allow the components to be coupled together through shared boundary conditions. Although the component-based paradigm is commonly used in software engineering, it has only recently been applied for modeling hydrologic and earth systems. As a result, research is needed to test and verify the applicability of the approach for modeling hydrologic systems. The objective of this work was therefore to investigate two aspects of using component-based software architecture for hydrologic modeling: (1) simulation of feedback loops between components that share a boundary condition and (2) data transfers between temporally misaligned model components. We investigated these topics using a simple case study where diffusion of mass is modeled across a water-sediment interface. We simulated the multimedia system using two model components, one for the water and one for the sediment, coupled using the Open Modeling Interface (OpenMI) standard. The results were compared with a more conventional numerical approach for solving the system where the domain is represented by a single multidimensional array. Results showed that the component-based approach was able to produce the same results obtained with the more conventional numerical approach. When the two components were temporally misaligned, we explored the use of different interpolation schemes to minimize mass balance error within the coupled system. The outcome of this work provides evidence that component-based modeling can be used to simulate complicated feedback loops between systems and guidance as to how different interpolation schemes minimize mass balance error introduced when components are temporally misaligned.

  8. A MALAT1/HIF-2α feedback loop contributes to arsenite carcinogenesis.

    PubMed

    Luo, Fei; Sun, Baofei; Li, Huiqiao; Xu, Yuan; Liu, Yi; Liu, Xinlu; Lu, Lu; Li, Jun; Wang, Qingling; Wei, Shaofeng; Shi, Le; Lu, Xiaolin; Liu, Qizhan; Zhang, Aihua

    2016-02-01

    Arsenic is well established as a human carcinogen, but the molecular mechanisms leading to arsenic-induced carcinogenesis are complex and elusive. It is also not known if lncRNAs are involved in arsenic-induced liver carcinogenesis. We have found that MALAT1, a non-coding RNA, is over-expressed in the sera of people exposed to arsenite and in hepatocellular carcinomas (HCCs), and MALAT1 has a close relation with the clinicopathological characteristics of HCC. In addition, hypoxia-inducible factor (HIF)-2α is up-regulated in HCCs, and MALAT1 and HIF-2α have a positive correlation in HCC tissues. During the malignant transformation of human hepatic epithelial (L-02) cells induced by a low concentration (2.0 μM) of arsenite, MALAT1 and HIF-2α are increased. In addition, arsenite-induced MALAT1 causes disassociation of the von Hippel-Lindau (VHL) protein from HIF-2α, therefore, alleviating VHL-mediated HIF-2α ubiquitination, which causes HIF-2α accumulation. In turn, HIF-2α transcriptionally regulates MALAT1, thus forming a positive feedback loop to ensure expression of arsenite-induced MALAT1 and HIF-2α, which are involved in malignant transformation. Moreover, MALAT1 and HIF-2α promote the invasive and metastatic capacities of arsenite-induced transformed L-02 cells and in HCC-LM3 cells. The capacities of MALAT1 and HIF-2α to promote tumor growth are validated in mouse xenograft models. In mice, arsenite induces an inflammatory response, and MALAT1 and HIF-2α are over-expressed. Together, these findings suggest that the MALAT1/HIF-2α feedback loop is involved in regulation of arsenite-induced malignant transformation. Our results not only confirm a novel mechanism involving reciprocal regulation between MALAT1 and HIF-2α, but also expand the understanding of the carcinogenic potential of arsenite. PMID:26735578

  9. A miR-130a-YAP positive feedback loop promotes organ size and tumorigenesis

    PubMed Central

    Shen, Shuying; Guo, Xiaocan; Yan, Huan; Lu, Yi; Ji, Xinyan; Li, Li; Liang, Tingbo; Zhou, Dawang; Feng, Xin-Hua; Zhao, Jonathan C; Yu, Jindan; Gong, Xing-Guo; Zhang, Lei; Zhao, Bin

    2015-01-01

    Organ size determination is one of the most intriguing unsolved mysteries in biology. Aberrant activation of the major effector and transcription co-activator YAP in the Hippo pathway causes drastic organ enlargement in development and underlies tumorigenesis in many human cancers. However, how robust YAP activation is achieved during organ size control remains elusive. Here we report that the YAP signaling is sustained through a novel microRNA-dependent positive feedback loop. miR-130a, which is directly induced by YAP, could effectively repress VGLL4, an inhibitor of YAP activity, thereby amplifying the YAP signals. Inhibition of miR-130a reversed liver size enlargement induced by Hippo pathway inactivation and blocked YAP-induced tumorigenesis. Furthermore, the Drosophila Hippo pathway target bantam functionally mimics miR-130a by repressing the VGLL4 homolog SdBP/Tgi. These findings reveal an evolutionarily conserved positive feedback mechanism underlying robustness of the Hippo pathway in size control and tumorigenesis. PMID:26272168

  10. Disease-association analysis of an inflammation-related feedback loop.

    PubMed

    Murakami, Masaaki; Harada, Masaya; Kamimura, Daisuke; Ogura, Hideki; Okuyama, Yuko; Kumai, Noriko; Okuyama, Azusa; Singh, Rajeev; Jiang, Jing-Jing; Atsumi, Toru; Shiraya, Sayaka; Nakatsuji, Yuji; Kinoshita, Makoto; Kohsaka, Hitoshi; Nishida, Makoto; Sakoda, Saburo; Miyasaka, Nobuyuki; Yamauchi-Takihara, Keiko; Yamaguchi-Takihara, Keiko; Hirano, Toshio

    2013-03-28

    The IL-6-triggered positive feedback loop for NFκB signaling (or the IL-6 amplifier/Inflammation amplifier) was originally discovered as a synergistic-activation signal that follows IL-17/IL-6 stimulation in nonimmune cells. Subsequent results from animal models have shown that the amplifier is activated by stimulation of NFκB and STAT3 and induces chemokines and inflammation via an NFκB loop. However, its role in human diseases is unclear. Here, we combined two genome-wide mouse screens with SNP-based disease association studies, revealing 1,700 genes related to the IL-6 amplifier, 202 of which showed 492 indications of association with ailments beyond autoimmune diseases. We followed up on ErbB1 from our list. Blocking ErbB1 signaling suppressed the IL-6 amplifier, whereas the expression of epiregulin, an ErbB1 ligand, was higher in patients with inflammatory diseases. These results indicate that the IL-6 amplifier is indeed associated with human diseases and disorders and that the identified genes may make for potential therapeutic targets. PMID:23434511

  11. Kuiper Airborne Observatory's Telescope Stabilization System: Disturbance Sensitivity Reduction Via Velocity Loop Feedback

    NASA Technical Reports Server (NTRS)

    Lawrence, David P.; Tsui, K. C.; Tucker, John; Mancini, Ronald E. (Technical Monitor)

    1995-01-01

    In July of 1994 the Kuiper Airborne Observatory's (KAO) Telescope Stabilization System (TSS) was upgraded to meet performance goals necessary to view the Shoemaker-Levy 9 comet collision with Jupiter. The KAO is a modified C-141 Aircraft supporting a 36 inch Infrared telescope used to gather and analyze astronomical data. Before the upgrade, the TSS exhibited approximately a 10 arc-second resolution pointing accuracy. The majority of the inaccuracy was attributable to aircraft vibration and wind buffeting entering through the aircraft's telescope door opening; in other words, the TSS was overly sensitive to external disturbances. Because of power limitations and noise requirements, improving the pointing accuracy of the telescope required more sophistication than simply raising the bandwidth as some classical control strategies might suggest. Instead, relationships were developed between the disturbance sensitivity and closed loop transfer functions. These relationships suggested that employing velocity feedback along with an increase in current loop gain would dramatically improve the pointing resolution of the TSS by decreasing the control system's sensitivity to external disturbances. With the implementation of some classical control techniques and the above philosophy, the KAO's TSS's resolution was improved to approximately 2-3 arc-seconds.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22395476

  13. A small-RNA-mediated negative feedback loop controls quorum-sensing dynamics in Vibrio harveyi

    PubMed Central

    Tu, Kimberly C; Waters, Christopher M; Svenningsen, Sine L; Bassler, Bonnie L

    2008-01-01

    The bioluminescent marine bacterium Vibrio harveyi uses a cell-to-cell communication process called quorum sensing (QS) to co-ordinate behaviours in response to changes in population density. QS is accomplished through the secretion and detection of extracellular signalling molecules called autoinducers. At the centre of the V. harveyi QS circuit are five small regulatory RNAs called Qrr1–5 which destabilize the mRNA of luxR, encoding LuxR, the master transcriptional regulator of QS target genes. Here we show that LuxR directly activates transcription of qrr2, qrr3 and qrr4, leading to the rapid downregulation of luxR. The LuxR-binding sites in the promoters of qrr2, qrr3 and qrr4 were identified and mutated to determine the consequences of this regulatory loop on QS dynamics. Disruption of the loop delays the transition from high to low cell density, and more significantly, decreases the cell density at which the population reaches a quorum. Our results suggest that feedback is essential for optimizing the dynamics of the transitions between individual and group behaviours. PMID:18808382

  14. A Novel Feedback Loop That Controls Bimodal Expression of Genetic Competence.

    PubMed

    Gamba, Pamela; Jonker, Martijs J; Hamoen, Leendert W

    2015-06-01

    Gene expression can be highly heterogeneous in isogenic cell populations. An extreme type of heterogeneity is the so-called bistable or bimodal expression, whereby a cell can differentiate into two alternative expression states. Stochastic fluctuations of protein levels, also referred to as noise, provide the necessary source of heterogeneity that must be amplified by specific genetic circuits in order to obtain a bimodal response. A classical model of bimodal differentiation is the activation of genetic competence in Bacillus subtilis. The competence transcription factor ComK activates transcription of its own gene, and an intricate regulatory network controls the switch to competence and ensures its reversibility. However, it is noise in ComK expression that determines which cells activate the ComK autostimulatory loop and become competent for genetic transformation. Despite its important role in bimodal gene expression, noise remains difficult to investigate due to its inherent stochastic nature. We adapted an artificial autostimulatory loop that bypasses all known ComK regulators to screen for possible factors that affect noise. This led to the identification of a novel protein Kre (YkyB) that controls the bimodal regulation of ComK. Interestingly, Kre appears to modulate the induction of ComK by affecting the stability of comK mRNA. The protein influences the expression of many genes, however, Kre is only found in bacteria that contain a ComK homologue and, importantly, kre expression itself is downregulated by ComK. The evolutionary significance of this new feedback loop for the reduction of transcriptional noise in comK expression is discussed. Our findings show the importance of mRNA stability in bimodal regulation, a factor that requires more attention when studying and modelling this non-deterministic developmental mechanism. PMID:26110430

  15. A Novel Feedback Loop That Controls Bimodal Expression of Genetic Competence

    PubMed Central

    Gamba, Pamela; Jonker, Martijs J.; Hamoen, Leendert W.

    2015-01-01

    Gene expression can be highly heterogeneous in isogenic cell populations. An extreme type of heterogeneity is the so-called bistable or bimodal expression, whereby a cell can differentiate into two alternative expression states. Stochastic fluctuations of protein levels, also referred to as noise, provide the necessary source of heterogeneity that must be amplified by specific genetic circuits in order to obtain a bimodal response. A classical model of bimodal differentiation is the activation of genetic competence in Bacillus subtilis. The competence transcription factor ComK activates transcription of its own gene, and an intricate regulatory network controls the switch to competence and ensures its reversibility. However, it is noise in ComK expression that determines which cells activate the ComK autostimulatory loop and become competent for genetic transformation. Despite its important role in bimodal gene expression, noise remains difficult to investigate due to its inherent stochastic nature. We adapted an artificial autostimulatory loop that bypasses all known ComK regulators to screen for possible factors that affect noise. This led to the identification of a novel protein Kre (YkyB) that controls the bimodal regulation of ComK. Interestingly, Kre appears to modulate the induction of ComK by affecting the stability of comK mRNA. The protein influences the expression of many genes, however, Kre is only found in bacteria that contain a ComK homologue and, importantly, kre expression itself is downregulated by ComK. The evolutionary significance of this new feedback loop for the reduction of transcriptional noise in comK expression is discussed. Our findings show the importance of mRNA stability in bimodal regulation, a factor that requires more attention when studying and modelling this non-deterministic developmental mechanism. PMID:26110430

  16. A feedback control loop for autonomous time synchronisation for mobile satellite systems, including satellites in any Earth orbit

    NASA Astrophysics Data System (ADS)

    Soprano, C.

    This paper presents the preliminary results of the design, analysis and simulation of a feedback control-loop for application to autonomous epoch synchronization in a satellite mobile synchronous communications system which includes communications satellites in non-geostationary Earth orbits and fast-moving mobile users.

  17. Distinct Roles of HDAC3 in the Core Circadian Negative Feedback Loop Are Critical for Clock Function.

    PubMed

    Shi, Guangsen; Xie, Pancheng; Qu, Zhipeng; Zhang, Zhihui; Dong, Zhen; An, Yang; Xing, Lijuan; Liu, Zhiwei; Dong, Yingying; Xu, Guoqiang; Yang, Ling; Liu, Yi; Xu, Ying

    2016-02-01

    In the core mammalian circadian negative feedback loop, the BMAL1-CLOCK complex activates the transcription of the genes Period (Per) and Cryptochrome (Cry). To close the negative feedback loop, the PER-CRY complex interacts with the BMAL1-CLOCK complex to repress its activity. These two processes are separated temporally to ensure clock function. Here, we show that histone deacetylase 3 (HDAC3) is a critical component of the circadian negative feedback loop by regulating both the activation and repression processes in a deacetylase activity-independent manner. Genetic depletion of Hdac3 results in low-amplitude circadian rhythms and dampened E-box-driven transcription. In subjective morning, HDAC3 is required for the efficient transcriptional activation process by regulating BMAL1 stability. In subjective night, however, HDAC3 blocks FBXL3-mediated CRY1 degradation and strongly promotes BMAL1 and CRY1 association. Therefore, these two opposing but temporally separated roles of HDAC3 in the negative feedback loop provide a mechanism for robust circadian gene expression. PMID:26776516

  18. Asymmetrisation of the profile of a thin dynamic holographic grating in a TV-locked optical feedback loop

    SciTech Connect

    Venediktov, Vladimir Yu; Ivanova, Natalya L; Freigang, N N; Laskin, V A

    2009-10-31

    A system for recording a dynamic holographic grating in an optically addressed liquid-crystal spatial light modulator is studied. The system provides the asymmetrisation of the grating profile by using a TV-locked optical feedback loop (nonlinear or adaptive interferometer). (laser applications and other topics in quantum electronics)

  19. The effect of sensory feedback on crayfish posture and locomotion: I. Experimental analysis of closing the loop.

    PubMed

    Chung, Bryce; Bacqué-Cazenave, Julien; Cofer, David W; Cattaert, Daniel; Edwards, Donald H

    2015-03-15

    The effect of proprioceptive feedback on the control of posture and locomotion was studied in the crayfish Procambarus clarkii (Girard). Sensory and motor nerves of an isolated crayfish thoracic nerve cord were connected to a computational neuromechanical model of the crayfish thorax and leg. Recorded levator (Lev) and depressor (Dep) nerve activity drove the model Lev and Dep muscles to move the leg up and down. These movements released and stretched a model stretch receptor, the coxobasal chordotonal organ (CBCO). Model CBCO length changes drove identical changes in the real CBCO; CBCO afferent responses completed the feedback loop. In a quiescent preparation, imposed model leg lifts evoked resistance reflexes in the Dep motor neurons that drove the leg back down. A muscarinic agonist, oxotremorine, induced an active state in which spontaneous Lev/Dep burst pairs occurred and an imposed leg lift excited a Lev assistance reflex followed by a Lev/Dep burst pair. When the feedback loop was intact, Lev/Dep burst pairs moved the leg up and down rhythmically at nearly three times the frequency of burst pairs when the feedback loop was open. The increased rate of rhythmic bursting appeared to result from the positive feedback produced by the assistance reflex. PMID:25540217

  20. A reduced model clarifies the role of feedback loops and time delays in the Drosophila circadian oscillator.

    PubMed

    Smolen, Paul; Baxter, Douglas A; Byrne, John H

    2002-11-01

    Although several detailed models of molecular processes essential for circadian oscillations have been developed, their complexity makes intuitive understanding of the oscillation mechanism difficult. The goal of the present study was to reduce a previously developed, detailed model to a minimal representation of the transcriptional regulation essential for circadian rhythmicity in Drosophila. The reduced model contains only two differential equations, each with time delays. A negative feedback loop is included, in which PER protein represses per transcription by binding the dCLOCK transcription factor. A positive feedback loop is also included, in which dCLOCK indirectly enhances its own formation. The model simulated circadian oscillations, light entrainment, and a phase-response curve with qualitative similarities to experiment. Time delays were found to be essential for simulation of circadian oscillations with this model. To examine the robustness of the simplified model to fluctuations in molecule numbers, a stochastic variant was constructed. Robust circadian oscillations and entrainment to light pulses were simulated with fewer than 80 molecules of each gene product present on average. Circadian oscillations persisted when the positive feedback loop was removed. Moreover, elimination of positive feedback did not decrease the robustness of oscillations to stochastic fluctuations or to variations in parameter values. Such reduced models can aid understanding of the oscillation mechanisms in Drosophila and in other organisms in which feedback regulation of transcription may play an important role. PMID:12414672

  1. Balanced bridge feedback control system

    NASA Technical Reports Server (NTRS)

    Lurie, Boris J. (Inventor)

    1990-01-01

    In a system having a driver, a motor, and a mechanical plant, a multiloop feedback control apparatus for controlling the movement and/or positioning of a mechanical plant, the control apparatus has a first local bridge feedback loop for feeding back a signal representative of a selected ratio of voltage and current at the output driver, and a second bridge feedback loop for feeding back a signal representative of a selected ratio of force and velocity at the output of the motor. The control apparatus may further include an outer loop for feeding back a signal representing the angular velocity and/or position of the mechanical plant.

  2. Balanced bridge feedback control system

    NASA Astrophysics Data System (ADS)

    Lurie, Boris J.

    1990-03-01

    In a system having a driver, a motor, and a mechanical plant, a multiloop feedback control apparatus for controlling the movement and/or positioning of a mechanical plant, the control apparatus has a first local bridge feedback loop for feeding back a signal representative of a selected ratio of voltage and current at the output driver, and a second bridge feedback loop for feeding back a signal representative of a selected ratio of force and velocity at the output of the motor. The control apparatus may further include an outer loop for feeding back a signal representing the angular velocity and/or position of the mechanical plant.

  3. Cable Crosstalk Suppression with Two-Wire Voltage Feedback Method for Resistive Sensor Array.

    PubMed

    Wu, Jianfeng; He, Shangshang; Li, Jianqing; Song, Aiguo

    2016-01-01

    Using a long, flexible test cable connected with a one-wire voltage feedback circuit, a resistive tactile sensor in a shared row-column fashion exhibited flexibility in robotic operations but suffered from crosstalk caused by the connected cable due to its wire resistances and its contacted resistances. Firstly, we designed a new non-scanned driving-electrode (VF-NSDE) circuit using two wires for every row line and every column line to reduce the crosstalk caused by the connected cables in the circuit. Then, an equivalent resistance expression of the element being tested (EBT) for the two-wire VF-NSDE circuit was analytically derived. Following this, the one-wire VF-NSDE circuit and the two-wire VF-NSDE circuit were evaluated by simulation experiments. Finally, positive features of the proposed method were verified with the experiments of a two-wire VF-NSDE prototype circuit. The experiment results show that the two-wire VF-NSDE circuit can greatly reduce the crosstalk error caused by the cables in the 2-D networked resistive sensor array. PMID:26907279

  4. Cable Crosstalk Suppression with Two-Wire Voltage Feedback Method for Resistive Sensor Array

    PubMed Central

    Wu, Jianfeng; He, Shangshang; Li, Jianqing; Song, Aiguo

    2016-01-01

    Using a long, flexible test cable connected with a one-wire voltage feedback circuit, a resistive tactile sensor in a shared row-column fashion exhibited flexibility in robotic operations but suffered from crosstalk caused by the connected cable due to its wire resistances and its contacted resistances. Firstly, we designed a new non-scanned driving-electrode (VF-NSDE) circuit using two wires for every row line and every column line to reduce the crosstalk caused by the connected cables in the circuit. Then, an equivalent resistance expression of the element being tested (EBT) for the two-wire VF-NSDE circuit was analytically derived. Following this, the one-wire VF-NSDE circuit and the two-wire VF-NSDE circuit were evaluated by simulation experiments. Finally, positive features of the proposed method were verified with the experiments of a two-wire VF-NSDE prototype circuit. The experiment results show that the two-wire VF-NSDE circuit can greatly reduce the crosstalk error caused by the cables in the 2-D networked resistive sensor array. PMID:26907279

  5. Design of a constant-voltage and constant-current controller with dual-loop and adaptive switching frequency control

    NASA Astrophysics Data System (ADS)

    Yingping, Chen; Zhiqian, Li

    2015-05-01

    A 5.0-V 2.0-A flyback power supply controller providing constant-voltage (CV) and constant-current (CC) output regulation without the use of an optical coupler is presented. Dual-close-loop control is proposed here due to its better regulation performance of tolerance over process and temperature compared with open loop control used in common. At the same time, the two modes, CC and CV, could switch to each other automatically and smoothly according to the output voltage level not sacrificing the regulation accuracy at the switching phase, which overcomes the drawback of the digital control scheme depending on a hysteresis comparator to change the mode. On-chip compensation using active capacitor multiplier technique is applied to stabilize the voltage loop, eliminate an additional package pin, and save on the die area. The system consumes as little as 100 mW at no-load condition without degrading the transient response performance by utilizing the adaptive switching frequency control mode. The proposed controller has been implemented in a commercial 0.35-μm 40-V BCD process, and the active chip area is 1.5 × 1.0 mm2. The total error of the output voltage due to line and load variations is less than ±1.7%.

  6. Regulation of lipogenesis via BHLHB2/DEC1 and ChREBP feedback looping

    SciTech Connect

    Iizuka, Katsumi; Horikawa, Yukio

    2008-09-12

    BHLHB2/DEC1 is a transcription factor implicated in cell proliferation, apoptosis, and metabolism, and is also known to play an important role in the regulation of the mammalian circadian rhythm. However, its precise role in metabolism remains unclear. We investigated the link between BHLHB2 and ChREBP, a glucose-activated transcription factor involved in the regulation of lipogenesis. Glucose stimulation and overexpression of dominant active ChREBP induced Bhlhb2 mRNA expression in rat hepatocytes. Deletion studies showed that ChoRE (-160 to -143 bp) in the mouse Bhlhb2 promoter region is functional in vivo. Overexpression of BHLHB2 inhibited glucose and ChREBP-mediated induction of rat Fasn and liver pyruvate kinase (Lpk) mRNA. ChIP assay demonstrated that BHLHB2 bound to ChoRE in the Fasn, Lpk, and Bhlhb2 promoter regions in vivo. In conclusion, BHLHB2 and ChREBP constitute a novel feedback loop involved in the regulation of lipogenesis.

  7. A positive feedback loop between Dumbfounded and Rolling pebbles leads to myotube enlargement in Drosophila

    PubMed Central

    Menon, Sree Devi; Osman, Zalina; Chenchill, Kho; Chia, William

    2005-01-01

    In Drosophila, myoblasts are subdivided into founders and fusion-competent myoblasts (fcm) with myotubes forming through fusion of one founder and several fcm. Duf and rolling pebbles 7 (Rols7; also known as antisocial) are expressed in founders, whereas sticks and stones (SNS) is present in fcm. Duf attracts fcm toward founders and also causes translocation of Rols7 from the cytoplasm to the fusion site. We show that Duf is a type 1 transmembrane protein that induces Rols7 translocation specifically when present intact and engaged in homophilic or Duf–SNS adhesion. Although its membrane-anchored extracellular domain functions as an attractant and is sufficient for the initial round of fusion, subsequent fusions require replenishment of Duf through cotranslocation with Rols7 tetratricopeptide repeat/coiled-coil domain-containing vesicles to the founder/myotube surface, causing both Duf and Rols7 to be at fusion sites between founders/myotubes and fcm. This implicates the Duf–Rols7 positive feedback loop to the occurrence of fusion at specific sites along the membrane and provides a mechanism by which the rate of fusion is controlled. PMID:15955848

  8. DSulfatase-1 fine-tunes Hedgehog patterning activity through a novel regulatory feedback loop

    PubMed Central

    Wojcinski, Alexandre; Nakato, Hiroshi; Soula, Cathy; Glise, Bruno

    2012-01-01

    Summary Sulfs are secreted sulfatases that catalyse removal of sulfate from Heparan Sulfate Proteoglycans (HSPGs) in the extracellular space. These enzymes are well known to regulate a number of crucial signalling pathways during development. In this study, we report that DSulfatase-1 (DSulf1), the unique Drosophila Sulf protein, is a regulator of Hedgehog (Hh) signalling during wing development. DSulf1 activity is required in both Hh source and Hh receiving cells for proper positioning of Hh target gene expression boundaries. As assessed by loss- and gain-of-function experiments in specific compartments, DSulf1 displays dual functions with respect to Hh signalling, acting as a positive regulator in Hh producing cells and a negative regulator in Hh receiving cells. In either domain, DSulf1 modulates Hh distribution by locally lowering the concentration of the morphogen at the apical pole of wing disc cells. Thus, we propose that DSulf1, by its desulfation catalytic activity, lowers Hh/HSPG interaction in both Hh source and target fields, thereby enhancing Hh release from its source of production and reducing Hh signalling activity in responding cells. Finally, we show that Dsulf1 pattern of expression is temporally regulated and depends on EGFR signalling, a Hh-dependent secondary signal in this tissue. Our data reveal a novel Hh regulatory feedback loop, involving DSulf1, which contributes to maintain and stabilize expression domains of Hh target genes during wing disc development. PMID:21806980

  9. A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation.

    PubMed

    Yang, Guang; Murashige, Danielle S; Humphrey, Sean J; James, David E

    2015-08-11

    The mechanistic target of rapamycin complex 2 (mTORC2) regulates cell survival and cytoskeletal organization by phosphorylating its AGC kinase substrates; however, little is known about the regulation of mTORC2 itself. It was previously reported that Akt phosphorylates the mTORC2 subunit SIN1 at T86, activating mTORC2 through a positive feedback loop, though another study reported that S6K phosphorylates SIN1 at the same site, inhibiting mTORC2 activity. We performed extensive analysis of SIN1 phosphorylation upon inhibition of Akt, S6K, and mTOR under diverse cellular contexts, and we found that, in all cell lines and conditions studied, Akt is the major kinase responsible for SIN1 phosphorylation. These findings refine the activation mechanism of the Akt-mTORC2 signaling branch as follows: PDK1 phosphorylates Akt at T308, increasing Akt kinase activity. Akt phosphorylates SIN1 at T86, enhancing mTORC2 kinase activity, which leads to phosphorylation of Akt S473 by mTORC2, thereby catalyzing full activation of Akt. PMID:26235620

  10. A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin states

    PubMed Central

    Bornstein, Chamutal; Winter, Deborah; Barnett-Itzhaki, Zohar; David, Eyal; Kadri, Sabah; Garber, Manuel; Amit, Ido

    2015-01-01

    During hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into alternative cell fates are not fully understood. Here, we identify cell-fate-determining transcription factors (TF) governing dendritic cell (DC) development by annotating the enhancer landscapes of the DC lineage. Combining these analyses with detailed over-expression, knockdown and ChIP-Seq studies, we show that Irf8 functions as a plasmacytoid DC epigenetic and fate-determining TF, regulating massive, cell-specific chromatin changes in thousands of pDC enhancers. Importantly, Irf8 forms a negative feedback loop with Cebpb, a monocyte-derived DC epigenetic fate-determining TF. We show that using this circuit logic, a pulse of TF expression can stably define epigenetic and transcriptional states, regardless of the microenvironment. More broadly, our study proposes a general paradigm that allows closely related cells with a similar set of signal-dependent factors to generate differential and persistent enhancer landscapes. PMID:25453760

  11. STRESS-INDUCED CHANGES IN ADRENAL NEUROPEPTIDE Y EXPRESSION ARE REGULATED BY A NEGATIVE FEEDBACK LOOP

    PubMed Central

    Wang, Qian; Whim, Matthew D.

    2013-01-01

    Neuropeptide Y is a co-transmitter that is synthesized by chromaffin cells in the adrenal medulla. During the fight-or-flight response these cells release NPY in addition to epinephrine and norepinephrine. Following the stress-induced reflex, the levels of NPY are increased as part of a homeostatic response that modulates catecholaminergic signaling. Here we examined the control of NPY expression in mice after brief exposure to the cold water forced swim test. This treatment led to a shift in NPY expression between two populations of chromaffin cells that reversed over the course of one week. When NPY(GFP) BAC transgenic animals were exposed to stress, there was an increase in cytoplasmic, nonsecretable GFP, indicating that stress increased NPY promoter activity. In vivo blockage of Y2 (but not Y1 or Y5) receptors increased basal adrenal NPY expression and so modulated the effects of stress. We conclude that release of NPY mediates a negative feedback loop that inhibits its own expression. Thus the levels of NPY are determined by a balance between the potentiating effects of stress and the tonic inhibitory actions of Y2 receptors. This may be an efficient way to ensure the levels of this modulator do not decline following intense sympathetic activity. PMID:23311866

  12. Flux module decomposition for parameter estimation in a multiple-feedback loop model of biochemical networks.

    PubMed

    Maeda, Kazuhiro; Minamida, Hiroshi; Yoshida, Keisuke; Kurata, Hiroyuki

    2013-03-01

    Computer simulation is an important technique to capture the dynamics of biochemical networks. Since few quantitative values are measured in vivo, the values for unmeasured parameters should be estimated so that the simulation agrees with the experimental data. Considering the sparsity and error rates of experimentally measured data, the first thing is not to find a numerically exact and global solution but to explore a variety of the plausible parameter solutions. To find many plausible parameter solutions without any biases, we developed the two-phase search (TPS) method. However, calculation complexity makes it hard for TPS to optimize a large-scale dynamic model. In this study divide-and-conquer methods are used to solve this problem. The flux module decomposition (FMD) is first proposed that separates a complex, large-scale dynamic model into multiple flux modules without deteriorating its basic control architectures. FMD is combined with TPS, named FMD-TPS, to find many plausible parameter solutions for a dynamic model. To demonstrate the feasibility of FMD-TPS, it is applied to the E. coli ammonia assimilation system that consists of multiple-feedback loops. The variability of the solutions is verified by measuring the space distribution of the parameter solution vectors and by defining the binary vectors checking the consistency with biological behaviors. Compared with non-decomposition methods, FMD-TPS efficiently explored a variety of plausible parameter solutions that reproduce the dynamic behaviors in vivo. PMID:22820677

  13. Procedure for preventing response strain on random interval schedules with a linear feedback loop.

    PubMed

    Reed, Phil

    2016-03-01

    An experiment examined the impact of a procedure designed to prevent response or extinction strain occurring on random interval schedules with a linear feedback loop (i.e., an RI+ schedule). Rats lever-pressed for food reinforcement on either a RI+ or a random interval (RI) schedule that was matched to the RI+ schedule in terms of reinforcement rate. Two groups of rats responded on an RI+ and two on an RI schedule matched for rate of reinforcement. One group on each schedule also received response-independent food if there had been no response for 60s, and response-independent food continued to be delivered on an RT-60 schedule until a response was made. Rats on the RI and RI+ obtained similar rates of reinforcement and had similar reinforced inter-response times to one another. On the schedules without response-independent food, rats had similar rates of response to one another. However, while the delivery of response-independent food reduced rates of response on an RI schedule, they enhanced response rates on an RI+ schedule. These results suggest that rats can display sensitivity to the molar aspects of the free-operant contingency, when procedures are implemented to reduce the impact of factors such as extinction-strain. PMID:26198776

  14. Casein kinase 1α–dependent feedback loop controls autophagy in RAS-driven cancers

    PubMed Central

    Cheong, Jit Kong; Zhang, Fuquan; Chua, Pei Jou; Bay, Boon Huat; Thorburn, Andrew; Virshup, David M.

    2015-01-01

    Activating mutations in the RAS oncogene are common in cancer but are difficult to therapeutically target. RAS activation promotes autophagy, a highly regulated catabolic process that metabolically buffers cells in response to diverse stresses. Here we report that casein kinase 1α (CK1α), a ubiquitously expressed serine/threonine kinase, is a key negative regulator of oncogenic RAS–induced autophagy. Depletion or pharmacologic inhibition of CK1α enhanced autophagic flux in oncogenic RAS–driven human fibroblasts and multiple cancer cell lines. FOXO3A, a master longevity mediator that transcriptionally regulates diverse autophagy genes, was a critical target of CK1α, as depletion of CK1α reduced levels of phosphorylated FOXO3A and increased expression of FOXO3A-responsive genes. Oncogenic RAS increased CK1α protein abundance via activation of the PI3K/AKT/mTOR pathway. In turn, elevated levels of CK1α increased phosphorylation of nuclear FOXO3A, thereby inhibiting transactivation of genes critical for RAS-induced autophagy. In both RAS-driven cancer cells and murine xenograft models, pharmacologic CK1α inactivation synergized with lysosomotropic agents to inhibit growth and promote tumor cell death. Together, our results identify a kinase feedback loop that influences RAS-dependent autophagy and suggest that targeting CK1α-regulated autophagy offers a potential therapeutic opportunity to treat oncogenic RAS–driven cancers. PMID:25798617

  15. Corp Regulates P53 in Drosophila melanogaster via a Negative Feedback Loop

    PubMed Central

    Chakraborty, Riddhita; Li, Ying; Zhou, Lei; Golic, Kent G.

    2015-01-01

    The tumor suppressor P53 is a critical mediator of the apoptotic response to DNA double-strand breaks through the transcriptional activation of pro-apoptotic genes. This mechanism is evolutionarily conserved from mammals to lower invertebrates, including Drosophila melanogaster. P53 also transcriptionally induces its primary negative regulator, Mdm2, which has not been found in Drosophila. In this study we identified the Drosophila gene companion of reaper (corp) as a gene whose overexpression promotes survival of cells with DNA damage in the soma but reduces their survival in the germline. These disparate effects are shared by p53 mutants, suggesting that Corp may be a negative regulator of P53. Confirming this supposition, we found that corp negatively regulates P53 protein level. It has been previously shown that P53 transcriptionally activates corp; thus, Corp produces a negative feedback loop on P53. We further found that Drosophila Corp shares a protein motif with vertebrate Mdm2 in a region that mediates the Mdm2:P53 physical interaction. In Corp, this motif mediates physical interaction with Drosophila P53. Our findings implicate Corp as a functional analog of vertebrate Mdm2 in flies. PMID:26230084

  16. Stress-induced changes in adrenal neuropeptide Y expression are regulated by a negative feedback loop.

    PubMed

    Wang, Qian; Whim, Matthew D

    2013-04-01

    Neuropeptide Y is a co-transmitter that is synthesized by chromaffin cells in the adrenal medulla. During the fight-or-flight response these cells release NPY in addition to epinephrine and norepinephrine. Following the stress-induced reflex, the levels of NPY are increased as part of a homeostatic response that modulates catecholaminergic signaling. Here, we examined the control of NPY expression in mice after brief exposure to the cold water forced swim test. This treatment led to a shift in NPY expression between two populations of chromaffin cells that reversed over the course of 1 week. When NPY(GFP) BAC transgenic animals were exposed to stress, there was an increase in cytoplasmic, non-secretable GFP, indicating that stress increased NPY promoter activity. In vivo blockage of Y2 (but not Y1 or Y5) receptors increased basal adrenal NPY expression and so modulated the effects of stress. We conclude that release of NPY mediates a negative feedback loop that inhibits its own expression. Thus, the levels of NPY are determined by a balance between the potentiating effects of stress and the tonic inhibitory actions of Y2 receptors. This may be an efficient way to ensure the levels of this modulator do not decline following intense sympathetic activity. PMID:23311866

  17. Ultrahigh resolution optical fiber strain sensor using dual Pound-Drever-Hall feedback loops.

    PubMed

    Chen, Jiageng; Liu, Qingwen; Fan, Xinyu; He, Zuyuan

    2016-03-01

    We present an ultrahigh resolution optical fiber strain sensor with a broad frequency range from quasi-static to several hundred hertz. The sensor consists of a π-phase shifted fiber Bragg grating for strain sensing and a fiber Fabry-Perot interferometer as reference. The laser carrier and sideband are locked to the reference and sensing elements, respectively, via two individual feedback loops, in which the Pound-Drever-Hall technique is employed to generate the error signals. The sampling rate is up to 500 samples/s in the demonstrational experiments, only limited by the updating rate of the frequency counter. The strain resolution exhibits a 1/f characteristic in the bandwidth of 0.01-250 Hz, and is better than 0.01 nϵ at 10 Hz with a dynamic range up to 149 dB. Compared with the traditional static strain sensors, the proposed sensor shows a great improvement in both resolution and sensing bandwidth, and can be a powerful tool for geophysical applications. PMID:26974117

  18. Corp Regulates P53 in Drosophila melanogaster via a Negative Feedback Loop.

    PubMed

    Chakraborty, Riddhita; Li, Ying; Zhou, Lei; Golic, Kent G

    2015-07-01

    The tumor suppressor P53 is a critical mediator of the apoptotic response to DNA double-strand breaks through the transcriptional activation of pro-apoptotic genes. This mechanism is evolutionarily conserved from mammals to lower invertebrates, including Drosophila melanogaster. P53 also transcriptionally induces its primary negative regulator, Mdm2, which has not been found in Drosophila. In this study we identified the Drosophila gene companion of reaper (corp) as a gene whose overexpression promotes survival of cells with DNA damage in the soma but reduces their survival in the germline. These disparate effects are shared by p53 mutants, suggesting that Corp may be a negative regulator of P53. Confirming this supposition, we found that corp negatively regulates P53 protein level. It has been previously shown that P53 transcriptionally activates corp; thus, Corp produces a negative feedback loop on P53. We further found that Drosophila Corp shares a protein motif with vertebrate Mdm2 in a region that mediates the Mdm2:P53 physical interaction. In Corp, this motif mediates physical interaction with Drosophila P53. Our findings implicate Corp as a functional analog of vertebrate Mdm2 in flies. PMID:26230084

  19. GRK2 Up-Regulation Creates a Positive Feedback Loop for Catecholamine Production in Chromaffin Cells.

    PubMed

    Jafferjee, Malika; Reyes Valero, Thairy; Marrero, Christine; McCrink, Katie A; Brill, Ava; Lymperopoulos, Anastasios

    2016-03-01

    Elevated sympathetic nervous system (SNS) activity aggravates several diseases, including heart failure. The molecular cause(s) underlying this SNS hyperactivity are not known. We have previously uncovered a neurohormonal mechanism, operating in adrenomedullary chromaffin cells, by which circulating catecholamine (CA) levels increase in heart failure: severe dysfunction of the adrenal α2-adrenergic receptors (ARs) due to the up-regulation of G protein-coupled receptor-kinase (GRK)-2, the kinase that desensitizes them. Herein we looked at the potential signaling mechanisms that bring about this GRK2 elevation in chromaffin cells. We found that chronic CA treatment of either PC12 or rat primary chromaffin cells can in itself result in GRK2 transcriptional up-regulation through α2ARs-Gi/o proteins-Src-ERK1/2. The resultant GRK2 increase severely enhances the α2AR desensitization/down-regulation elevating not only CA release but also CA biosynthesis, as evidenced by tyrosine hydroxylase up-regulation. Finally, GRK2 knockdown leads to enhanced apoptosis of PC12 cells, indicating an essential role for GRK2 in chromaffin cell homeostasis/survival. In conclusion, chromaffin cell GRK2 mediates a positive feedback loop that feeds into CA secretion, thereby enabling the adrenomedullary component of the SNS to turn itself on. PMID:26849467

  20. The NKD1/Rac1 feedback loop regulates the invasion and migration ability of hepatocarcinoma cells.

    PubMed

    Li, Jie; Zhang, Sheng; Hu, Qing; Zhang, Kang; Jin, Jianbin; Zheng, Xuqing; Yin, Zhenyu; Wang, Xiaomin

    2016-01-01

    Hepatocellular carcinoma (HCC) is complicated by aggressive migration and invasion, which contribute to the increased mortality of HCC patients. The NKD1 protein is abnormally expressed in many neoplasms and plays an important role in tumor progression. However, the regulation and underlying molecular mechanisms of NKD1 in HCC cell invasion and migration remain poorly understood. In the present study, ectopic expression of NKD1 in HCC cells attenuated migration and invasion in vitro and in vivo by down-regulating Rac1 expression level and activity, which affected the HCC cell cytoskeleton and E-cadherin expression. Mechanistic studies showed that NKD1 interacted with Rac1 in the cytoplasm and promoted its degradation by the ubiquitin-proteasome pathway. Over-expression of Rac1 enhanced the transcription of the NKD1 gene and protein expression conversely owing to its negative regulation of EZH2. Analysis of clinical samples showed that abnormal expression of NKD1 and Rac1 was associated with the poor prognosis of HCC patients. In summary, our data indicate a new role for NKD1 as a regulator of HCC cell invasion and migration via a feedback loop involving Rac1. PMID:27231134

  1. Caspase-1 activity affects AIM2 speck formation/stability through a negative feedback loop

    PubMed Central

    Juruj, C.; Lelogeais, V.; Pierini, R.; Perret, M.; Py, B. F.; Jamilloux, Y.; Broz, P.; Ader, F.; Faure, M.; Henry, T.

    2013-01-01

    The inflammasome is an innate immune signaling platform leading to caspase-1 activation, maturation of pro-inflammatory cytokines and cell death. Recognition of DNA within the host cytosol induces the formation of a large complex composed of the AIM2 receptor, the ASC adaptor and the caspase-1 effector. Francisella tularensis, the agent of tularemia, replicates within the host cytosol. The macrophage cytosolic surveillance system detects Francisella through the AIM2 inflammasome. Upon Francisella novicida infection, we observed a faster kinetics of AIM2 speck formation in ASCKO and Casp1KO as compared to WT macrophages. This observation was validated by a biochemical approach thus demonstrating for the first time the existence of a negative feedback loop controlled by ASC/caspase-1 that regulates AIM2 complex formation/stability. This regulatory mechanism acted before pyroptosis and required caspase-1 catalytic activity. Our data suggest that sublytic caspase-1 activity could delay the formation of stable AIM2 speck, an inflammasome complex associated with cell death. PMID:23630667

  2. An assessment of overall open-loop "gain" of CO2-ventilation feedback control system in hypoxia.

    PubMed

    Masuyama, H; Akiyama, S; Honda, Y

    1985-01-01

    Overall open-loop gain of the CO2-ventilation feedback control system in hypoxia (GHCO2) was determined on 8 male and one female healthy subjects. They breathed in a closed circuit, and were subjected to the progressive hypoxia test. This procedure was first conducted without dead space (DS), then with 250, 500, and finally 750 ml DS, consecutively. GHCO2 was calculated by dividing the slope of the CO2 response curve (S) by that of the metabolic hyperbola (SL). GHCO2 was considerably larger than the overall open-loop gain of the O2-ventilation feedback control system (GO2) previously obtained. This was ascribed to the facts that S was larger than the slope of the hypoxia response curve, and that the absolute value of SL in GHCO2 was smaller than that in GO2. PMID:3934438

  3. A SOLAS challenge: How can we test test feedback loops involving air-sea exchange?

    NASA Astrophysics Data System (ADS)

    Huebert, B. J.

    2004-12-01

    It is now well accepted that the Earth System links biological and physical processes in the water, on land, and in the air, creating countless feedback loops and dependencies that are at best difficult to quantify. One example of interest to SOLAS scientists is the suspension and long-range transport of dust from Asia, which may or may not interact with acidic air pollutants, that may increase the biological availability of iron, thereby increasing primary productivity in parts of the Pacific. This could increase DMS emissions and modify the radiative impact of Pacific clouds, affecting the climate and the hydrological system that limits the amount of dust lofted each year. Air-sea exchange is central to many such feedbacks: Variations in productivity in upwelling waters off Peru probably change DMS emissions and modify the stratocumulus clouds that blanket that region, thereby feeding back to productivity. The disparate time and space scales of the controlling processes make it difficult to observationally constrain such systems without the use of multi-year time-series and intensive multiplatform process studies. Unfortunately, much of the infrastructure for funding Earth science is poorly suited for supporting multidisciplinary research. For example, NSF's program managers are organized into disciplines and sub-disciplines, and rely on disciplinary reviewer communities that are protective of their slices of the funding pie. It is easy to find authors of strong, innovative, cross-disciplinary (yet unsuccessful) proposals who say they'll never try it again, because there is so little institutional support for interfacial research. Facility issues also complicate multidisciplinary projects, since there are usually several allocating groups that don't want to commit their ships, airplanes, or towers until the other groups have done so. The result is that there are very few examples of major interdisciplinary projects, even though IGBP core programs have articulated the need for them. Achieving IGBP's goals requires new observational and organizational strategies. Some relatively modest changes in the ways that facilities and grants are awarded could make it possible to do multidisciplinary experiments of the type described in the SOLAS Science Plan and Implementation Strategy.

  4. The ZEB1/miR-200c feedback loop regulates invasion via actin interacting proteins MYLK and TKS5

    PubMed Central

    Stemmler, Marc P.; Kleemann, Julia A.; Brabletz, Thomas; Brabletz, Simone

    2015-01-01

    Epithelial to mesenchymal transition (EMT) is a developmental process which is aberrantly activated during cancer invasion and metastasis. Elevated expression of EMT-inducers like ZEB1 enables tumor cells to detach from the primary tumor and invade into the surrounding tissue. The main antagonist of ZEB1 in controlling EMT is the microRNA-200 family that is reciprocally linked to ZEB1 in a double negative feedback loop. Here, we further elucidate how the ZEB1/miR-200 feedback loop controls invasion of tumor cells. The process of EMT is attended by major changes in the actin cytoskeleton. Via in silico screening of genes encoding for actin interacting proteins, we identified two novel targets of miR-200c - TKS5 and MYLK (MLCK). Co-expression of both genes with ZEB1 was observed in several cancer cell lines as well as in breast cancer patients and correlated with low miR-200c levels. Depletion of TKS5 or MYLK in breast cancer cells reduced their invasive potential and their ability to form invadopodia. Whereas TKS5 is known to be a major component, we could identify MYLK as a novel player in invadopodia formation. In summary, TKS5 and MYLK represent two mediators of invasive behavior of cancer cells that are regulated by the ZEB1/miR-200 feedback loop. PMID:26334100

  5. Does a short loop feedback mechanism for the control of luteinizing hormone secretion exist in the ewe?

    PubMed

    Skinner, D C; Evans, N P; Malpaux, B

    1997-10-01

    It is not known whether a short loop feedback mechanism for the regulation of LH exists in sheep. This study on ovariectomized ewes investigated whether a bolus injection (10, 1, and 0.1 microg LH or 1 microg BSA; n 4) or a 3-h continuous infusion of exogenous LH (100 or 1 ng/min; n = 7) into the third ventricle through a permanent indwelling cannula could influence the activity of the GnRH pulse generator, as determined by measurement of endogenous LH secretion. To assess the potential for involvement in a LH short loop feedback system and to estimate the level of LH in the hypothalamic milieu, the concentrations of LH in the peripheral circulation, portal circulation, and third ventricle were measured during an estradiol-induced preovulatory LH surge (n = 4). Neither the bolus nor continuous administration of LH into the third ventricle had any effect on the mean interpulse interval, nadir, pulse amplitude, or circulating level of systemic LH. Furthermore, despite portal LH concentrations being more than 20-fold higher than jugular LH concentrations, LH levels in third ventricular cerebrospinal fluid remained barely detectable and did not reflect dynamic secretory events in the peripheral or hypothalamo-hypophyseal portal blood. These data demonstrate that in ewes, little pituitary LH reaches the third ventricle, and the small amount that does is unable to affect peripheral gonadotropin release. Our study suggests, therefore, that a short loop feedback system for LH does not exist in the ewe. PMID:9322933

  6. On the nonlinear feedback loop and energy cycle of the non-dissipative Lorenz model

    NASA Astrophysics Data System (ADS)

    Shen, B.-W.

    2014-04-01

    In this study, we discuss the role of the nonlinear terms and linear (heating) term in the energy cycle of the three-dimensional (X-Y-Z) non-dissipative Lorenz model (3D-NLM). (X, Y, Z) represent the solutions in the phase space. We first present the closed-form solution to the nonlinear equation d2 X/dτ2+ (X2/2)X = 0, τ is a non-dimensional time, which was never documented in the literature. As the solution is oscillatory (wave-like) and the nonlinear term (X2) is associated with the nonlinear feedback loop, it is suggested that the nonlinear feedback loop may act as a restoring force. We then show that the competing impact of nonlinear restoring force and linear (heating) force determines the partitions of the averaged available potential energy from Y and Z modes, respectively, denoted as APEY and APEZ. Based on the energy analysis, an energy cycle with four different regimes is identified with the following four points: A(X, Y) = (0,0), B = (Xt, Yt), C = (Xm, Ym), and D = (Xt, -Yt). Point A is a saddle point. The initial perturbation (X, Y, Z) = (0, 1, 0) gives (Xt, Yt) = ( 2σr , r) and (Xm, Ym) = (2 σr , 0). σ is the Prandtl number, and r is the normalized Rayleigh number. The energy cycle starts at (near) point A, A+ = (0, 0+) to be specific, goes through B, C, and D, and returns back to A, i.e., A- = (0,0-). From point A to point B, denoted as Leg A-B, where the linear (heating) force dominates, the solution X grows gradually with { KE↑, APEY↓, APEZ↓}. KE is the averaged kinetic energy. We use the upper arrow (↑) and down arrow (↓) to indicate an increase and decrease, respectively. In Leg B-C (or C-D) where nonlinear restoring force becomes dominant, the solution X increases (or decreases) rapidly with KE↑, APEY↑, APEZ↓ (or KE↓, APEY↓, APEZ↑). In Leg D-A, the solution X decreases slowly with {KE↓, APEY↑, APEZ↑ }. As point A is a saddle point, the aforementioned cycle may be only half of a "big" cycle, displaying the wing pattern of a glasswinged butterfly, and the other half cycle is antisymmetric with respect to the origin, namely B = (-Xt, -Yt), C = (-Xm, 0), and D = (-Xt, Yt).

  7. Microfluidic device incorporating closed loop feedback control for uniform and tunable production of micro-droplets.

    PubMed

    Miller, Erik; Rotea, Mario; Rothstein, Jonathan P

    2010-05-21

    Both micro- and nanofluidics are finding increasing use in the growing toolbox of nanotechnology; for the production of nanoparticles, and as micro-reactors for carefully controlled chemical reactions. These laboratories-on-a-chip hold vast potential for industrial application, however, only the most simple are truly starting to emerge as commercially viable, particularly in the area of droplet formation and emulsion creation. In order to automate droplet production with a desired size and dispersity, we have designed a microfluidic-based technology utilizing elementary microchannel geometries in combination with a closed loop feedback system to control the continuous- and dispersed-phase flow rates. Both the device geometry and control system have been optimized to allow for the production of a tunable emulsion. By utilizing discrete linear control theory, the device is able to produce the desired results with little to no prior knowledge of the fluid material properties to be used in either phase. We present our results from initial development using flow-focusing microfluidic geometry for droplet formation, computer-tethered syringe pumps to individually control the continuous and dispersed phase flow rates, a high-speed camera, and a controller and driver system for the optical measurements and pumps, respectively. We will show the efficacy of this technique for Newtonian and viscoelastic liquids, with and without the presence of surfactants. It can be envisioned that through careful control optimization, such a system can be developed to a point that will allow the production of "designer" emulsions with droplets eventually reaching the nanoscale. PMID:20445883

  8. A Feedback Loop between Dynamin and Actin Recruitment during Clathrin-Mediated Endocytosis

    PubMed Central

    Taylor, Marcus J.; Lampe, Marko; Merrifield, Christien J.

    2012-01-01

    Clathrin-mediated endocytosis proceeds by a sequential series of reactions catalyzed by discrete sets of protein machinery. The final reaction in clathrin-mediated endocytosis is membrane scission, which is mediated by the large guanosine triophosphate hydrolase (GTPase) dynamin and which may involve the actin-dependent recruitment of N-terminal containing BIN/Amphiphysin/RVS domain containing (N-BAR) proteins. Optical microscopy has revealed a detailed picture of when and where particular protein types are recruited in the ∼20–30 s preceding scission. Nevertheless, the regulatory mechanisms and functions that underpin protein recruitment are not well understood. Here we used an optical assay to investigate the coordination and interdependencies between the recruitment of dynamin, the actin cytoskeleton, and N-BAR proteins to individual clathrin-mediated endocytic scission events. These measurements revealed that a feedback loop exists between dynamin and actin at sites of membrane scission. The kinetics of dynamin, actin, and N-BAR protein recruitment were modulated by dynamin GTPase activity. Conversely, acute ablation of actin dynamics using latrunculin-B led to a ∼50% decrease in the incidence of scission, an ∼50% decrease in the amplitude of dynamin recruitment, and abolished actin and N-BAR recruitment to scission events. Collectively these data suggest that dynamin, actin, and N-BAR proteins work cooperatively to efficiently catalyze membrane scission. Dynamin controls its own recruitment to scission events by modulating the kinetics of actin and N-BAR recruitment to sites of scission. Conversely actin serves as a dynamic scaffold that concentrates dynamin and N-BAR proteins at sites of scission. PMID:22505844

  9. Positive Feedback-Loop of Telomerase Reverse Transcriptase and 15-Lipoxygenase-2 Promotes Pulmonary Hypertension

    PubMed Central

    Shen, Tingting; Ma, Jun; Zhang, Lei; Yu, Xiufeng; Liu, Mengmeng; Hou, Yunlong; Wang, Yanyan; Ma, Cui; Li, Shuzhen; Zhu, Daling

    2013-01-01

    Objective Pulmonary hypertension (PH) is characterized with pulmonary vasoconstriction and vascular remodeling mediated by 15-lipoxygenase (15-LO)/15-hydroxyeicosatetraenoic acid (15-HETE) according to our previous studies. Meanwhile, telomerase reverse transcriptase (TERT) activity is highly correlated with vascular injury and remodeling, suggesting that TERT may be an essential determinant in the development of PH. The aim of this study was to determine the contribution and molecular mechanisms of TERT in the pathogenesis of PH. Approach and Results We measured the right ventricular systolic pressure (RVSP) and ventricular weight, analyzed morphometric change of the pulmonary vessels in the hypoxia or monocrotaline treated rats. Bromodeoxyuridine incorporation, transwell assay and flow cytometry in pulmonary smooth muscle cells were performed to investigate the roles and relationship of TERT and 15-LO/15-HETE in PH. We revealed that the expression of TERT was increased in pulmonary vasculature of patients with PH and in the monocrotaline or hypoxia rat model of PH. The up-regulation of TERT was associated with experimental elevated RVSP and pulmonary vascular remodeling. Coimmunoprecipitation experiments identified TERT as a novel interacting partner of 15-LO-2. TERT and 15-LO-2 augmented protein expression of each other. In addition, the proliferation, migration and cell-cycle transition from G0/G1 phase to S phase induced by hypoxia were inhibited by TERT knockdown, which were rescued by 15-HETE addition. Conclusions These results demonstrate that TERT regulates pulmonary vascular remodeling. TERT and 15-LO-2 form a positive feedback loop and together promote proliferation and migration of pulmonary artery smooth muscle cells, creating a self-amplifying circuit which propels pulmonary hypertension. PMID:24376652

  10. The visualization of the acoustic feedback loop in impinging underexpanded supersonic jet flows using ultra-high frame rate Schlieren

    NASA Astrophysics Data System (ADS)

    Mitchell, Daniel; Honnery, Damon; Soria, Julio

    2011-11-01

    An acoustic feedback model for supersonic jet impingement has been proposed in past literature. Due to the inherent difficulty in measuring highly transient phenomena, models of the feedback process have mostly relied on inference, and comparison to similar subsonic flows. Through the use of ultra-high speed cameras operating at one million frames per second, it has been possible to directly visualize the acoustic feedback loop for the first time. Time resolved Schlieren and shadowgraph image sequences capture the interaction of upstream travelling acoustic waves with the shear layer at the nozzle lip and shock structures within the jet core. The acoustic forcing at the nozzle lip produces a sinusoid like perturbation in the shear layer that is highly transient both temporally and spatially. This perturbation grows rapidly into a Kelvin-Helmholtz like vortex ring. These time resolved measurements offer new insights into the fundamental physical mechanisms governing the acoustic feedback loop in supersonic jet impingement. The authors acknowledge the support of the ARC Discovery and LIEF grants.

  11. ASDTIC: A feedback control innovation

    NASA Technical Reports Server (NTRS)

    Lalli, V. R.; Schoenfeld, A. D.

    1972-01-01

    The ASDTIC (Analog Signal to Discrete Time Interval Converter) control subsystem provides precise output control of high performance aerospace power supplies. The key to ASDTIC operation is that it stably controls output by sensing output energy change as well as output magnitude. The ASDTIC control subsystem and control module were developed to improve power supply performance during static and dynamic input voltage and output load variations, to reduce output voltage or current regulation due to component variations or aging, to maintain a stable feedback control with variations in the loop gain or loop time constants, and to standardize the feedback control subsystem for power conditioning equipment.

  12. ASDTIC - A feedback control innovation.

    NASA Technical Reports Server (NTRS)

    Lalli, V. R.; Schoenfeld, A. D.

    1972-01-01

    The ASDTIC (analog signal to discrete time interval converter) control subsystem provides precise output control of high performance aerospace power supplies. The key to ASDTIC operation is that it stably controls output by sensing output energy change as well as output magnitude. The ASDTIC control subsystem and control module were developed to improve power supply performance during static and dynamic input voltage and output load variations, to reduce output voltage or current regulation due to component variations or aging, to maintain a stable feedback control with variations in the loop gain or loop time constants, and to standardize the feedback control subsystem for power conditioning equipment.

  13. A MicroRNA-Mediated Positive Feedback Regulatory Loop of the NF-κB Pathway in Litopenaeus vannamei.

    PubMed

    Zuo, Hongliang; Yuan, Jia; Chen, Yonggui; Li, Sedong; Su, Ziqi; Wei, Erman; Li, Chaozheng; Weng, Shaoping; Xu, Xiaopeng; He, Jianguo

    2016-05-01

    In the evolutionarily conserved canonical NF-κB pathway, degradation of the NF-κB inhibitor IκB in the cytoplasmic NF-κB/IκB complex allows the liberated NF-κB to translocate into the nucleus to activate various target genes. The regulatory mechanism governing this process needs further investigation. In this study, a novel microRNA, temporarily named miR-1959, was first identified from an invertebrate Litopenaeus vannamei miR-1959 targets the 3'-untranslated region of the IκB homolog Cactus gene and reduces the protein level of Cactus in vivo, whereas the NF-κB homolog Dorsal directly binds the miR-1959 promoter to activate its transcription. Therefore, miR-1959 mediates a positive feedback regulatory loop, in that Dorsal activates miR-1959 expression, and in turn, miR-1959 inhibits the expression of Cactus, further leading to enhanced activation of Dorsal. Moreover, miR-1959 regulates the expression of many antimicrobial peptides in vivo and is involved in antibacterial immunity. To our knowledge, it is the first discovery of a microRNA-mediated feedback loop that directly regulates the NF-κB/IκB complex. This positive feedback loop could collaborate with the known NF-κB/IκB negative loop to generate a dynamic balance to regulate the activity of NF-κB, thus constituting an effective regulatory mechanism at the critical node of the NF-κB pathway. PMID:26994223

  14. OncomiR Addiction Is Generated by a miR-155 Feedback Loop in Theileria-Transformed Leukocytes

    PubMed Central

    Medjkane, Souhila; Perichon, Martine; Yin, Qinyan; Flemington, Erik; Weitzman, Matthew D.; Weitzman, Jonathan B.

    2013-01-01

    The intracellular parasite Theileria is the only eukaryote known to transform its mammalian host cells. We investigated the host mechanisms involved in parasite-induced transformation phenotypes. Tumour progression is a multistep process, yet ‘oncogene addiction’ implies that cancer cell growth and survival can be impaired by inactivating a single gene, offering a rationale for targeted molecular therapies. Furthermore, feedback loops often act as key regulatory hubs in tumorigenesis. We searched for microRNAs involved in addiction to regulatory loops in leukocytes infected with Theileria parasites. We show that Theileria transformation involves induction of the host bovine oncomiR miR-155, via the c-Jun transcription factor and AP-1 activity. We identified a novel miR-155 target, DET1, an evolutionarily-conserved factor involved in c-Jun ubiquitination. We show that miR-155 expression led to repression of DET1 protein, causing stabilization of c-Jun and driving the promoter activity of the BIC transcript containing miR-155. This positive feedback loop is critical to maintain the growth and survival of Theileria-infected leukocytes; transformation is reversed by inhibiting AP-1 activity or miR-155 expression. This is the first demonstration that Theileria parasites induce the expression of host non-coding RNAs and highlights the importance of a novel feedback loop in maintaining the proliferative phenotypes induced upon parasite infection. Hence, parasite infection drives epigenetic rewiring of the regulatory circuitry of host leukocytes, placing miR-155 at the crossroads between infection, regulatory circuits and transformation. PMID:23637592

  15. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK–NF-κB signaling pathway

    SciTech Connect

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun; Gu, Wei; Wan, Xiao-Ping

    2014-03-28

    Highlights: • IL-6 could promote endometrial cancer cells proliferation. • IL-6 promotes its own production through an autocrine feedback loop. • ERK and NF-κB pathway inhibitors inhibit IL-6 production and tumor growth. • IL-6 secretion relies on the activation of ERK–NF-κB pathway axis. • An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK–NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.

  16. A closed-loop human simulator for investigating the role of feedback control in brain-machine interfaces

    PubMed Central

    Cunningham, John P.; Nuyujukian, Paul; Gilja, Vikash; Chestek, Cindy A.; Ryu, Stephen I.

    2011-01-01

    Neural prosthetic systems seek to improve the lives of severely disabled people by decoding neural activity into useful behavioral commands. These systems and their decoding algorithms are typically developed “offline,” using neural activity previously gathered from a healthy animal, and the decoded movement is then compared with the true movement that accompanied the recorded neural activity. However, this offline design and testing may neglect important features of a real prosthesis, most notably the critical role of feedback control, which enables the user to adjust neural activity while using the prosthesis. We hypothesize that understanding and optimally designing high-performance decoders require an experimental platform where humans are in closed-loop with the various candidate decode systems and algorithms. It remains unexplored the extent to which the subject can, for a particular decode system, algorithm, or parameter, engage feedback and other strategies to improve decode performance. Closed-loop testing may suggest different choices than offline analyses. Here we ask if a healthy human subject, using a closed-loop neural prosthesis driven by synthetic neural activity, can inform system design. We use this online prosthesis simulator (OPS) to optimize “online” decode performance based on a key parameter of a current state-of-the-art decode algorithm, the bin width of a Kalman filter. First, we show that offline and online analyses indeed suggest different parameter choices. Previous literature and our offline analyses agree that neural activity should be analyzed in bins of 100- to 300-ms width. OPS analysis, which incorporates feedback control, suggests that much shorter bin widths (25–50 ms) yield higher decode performance. Second, we confirm this surprising finding using a closed-loop rhesus monkey prosthetic system. These findings illustrate the type of discovery made possible by the OPS, and so we hypothesize that this novel testing approach will help in the design of prosthetic systems that will translate well to human patients. PMID:20943945

  17. Identification of a negative feedback loop in biological oxidant formation fegulated by 4-hydroxy-2-(E)-nonenal

    PubMed Central

    Gatbonton-Schwager, Tonibelle N.; Sadhukhan, Sushabhan; Zhang, Guo-Fang; Letterio, John J.; Tochtrop, Gregory P.

    2014-01-01

    4-Hydroxy-2-(E)-nonenal (4-HNE) is one of the major lipid peroxidation product formed during oxidative stress. At high concentrations, 4-HNE is cytotoxic and exerts deleterious effects that are often associated with the pathology of oxidative stress-driven disease. Alternatively, at low concentrations it functions as a signaling molecule that can activate protective pathways including the antioxidant Nrf2-Keap1 pathway. Although these biphasic signaling properties have been enumerated in many diseases and pathways, it has yet to be addressed whether 4-HNE has the capacity to modulate oxidative stress-driven lipid peroxidation. Here we report an auto-regulatory mechanism of 4-HNE via modulation of the biological oxidant nitric oxide (NO). Utilizing LPS-activated macrophages to induce biological oxidant production, we demonstrate that 4-HNE modulates NO levels via inhibition of iNOS expression. We illustrate a proposed model of control of NO formation whereby at low concentrations of 4-HNE a negative feedback loop maintains a constant level of NO production with an observed inflection at approximately 1 µM, while at higher 4-HNE concentrations positive feedback is observed. Further, we demonstrate that this negative feedback loop of NO production control is dependent on the Nrf2-Keap1 signaling pathway. Taken together, the careful regulation of NO production by 4-HNE argues for a more fundamental role of this lipid peroxidation product in normal physiology. PMID:25009777

  18. Hyperosmotic Shock Engages Two Positive Feedback Loops through Caspase-3-dependent Proteolysis of JNK1-2 and Bid.

    PubMed

    Yue, Jicheng; Ben Messaoud, Nabil; López, José M

    2015-12-18

    Hyperosmotic shock induces early calpain activation, Smac/DIABLO release from the mitochondria, and p38/JNK activation in Xenopus oocytes. These pathways regulate late cytochrome c release and caspase-3 activation. Here, we show that JNK1-1 and JNK1-2 are activated early by osmostress, and sustained activation of both isoforms accelerates the apoptotic program. When caspase-3 is activated, JNK1-2 is proteolyzed at Asp-385 increasing the release of cytochrome c and caspase-3 activity, thereby creating a positive feedback loop. Expression of Bcl-xL markedly reduces hyperosmotic shock-induced apoptosis. In contrast, expression of Bid induces rapid caspase-3 activation, even in the absence of osmostress, which is blocked by Bcl-xL co-expression. In these conditions a significant amount of Bid in the cytosol is mono- and bi-ubiquitinated. Caspase-3 activation by hyperosmotic shock induces proteolysis of Bid and mono-ubiquitinated Bid at Asp-52 increasing the release of cytochrome c and caspase-3 activation, and thus creating a second positive feedback loop. Revealing the JNK isoforms and the loops activated by osmostress could help to design better treatments for human diseases caused by perturbations in fluid osmolarity. PMID:26511318

  19. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK-NF-κB signaling pathway.

    PubMed

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun; Gu, Wei; Wan, Xiao-Ping

    2014-03-28

    Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK-NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma. PMID:24582558

  20. An affinity-effect relationship for microbial communities in plant-soil feedback loops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant-soil feedback involving soil microorganisms can regulate plant populations. To participate in plant-soil feedback, microorganisms must display an affinity for plant species, and they must produce consistent effects on plant growth. We tested the validity and strength of microbial affinity-effe...

  1. Hyperglycemia and hyperlipidemia blunts the Insulin-Inpp5f negative feedback loop in the diabetic heart.

    PubMed

    Bai, Danna; Zhang, Yajun; Shen, Mingzhi; Sun, Yongfeng; Xia, Qing; Zhang, Yingmei; Liu, Xuedong; Wang, Haichang; Yuan, Lijun

    2016-01-01

    The leading cause of death in diabetic patients is diabetic cardiomyopathy, in which alteration of Akt signal plays an important role. Inpp5f is recently found to be a negative regulator of Akt signaling, while its expression and function in diabetic heart is largely unknown. In this study, we found that in both the streptozotocin (STZ) and high fat diet (HFD) induced diabetic mouse models, Inpp5f expression was coordinately regulated by insulin, blood glucose and lipid levels. Increased Inpp5f was inversely correlated with the cardiac function. Further studies revealed that Insulin transcriptionally activated Inpp5f in an Sp1 dependent manner, and increased Inpp5f in turn reduced the phosphorylation of Akt, forming a negative feedback loop. The negative feedback plays a protective role under diabetic condition. However, high blood glucose and lipid, which are characteristics of uncontrolled diabetes and type 2 diabetes, increased Inpp5f expression through activation of NF-κB, blunts the protective feedback. Thus, our study has revealed that Inpp5f provides as a negative feedback regulator of insulin signaling and downregulation of Inpp5f in diabetes is cardioprotective. Increased Inpp5f by hyperglycemia and hyperlipidemia is an important mediator of diabetic cardiomyopathy and is a promising therapeutic target for the disease. PMID:26908121

  2. In vivo argon laser vascular welding using thermal feedback: open and closed loop patency and collagen crosslinking

    SciTech Connect

    Small, W., LLNL

    1997-02-28

    An in vivo study of vascular welding with a fiber-delivered argon laser was conducted using a canine model. Longitudinal arteriotomies and venotomies were treated on femoral vein and artery. Laser energy was delivered to the vessel wall via a 400 {micro}m optical fiber. The surface temperature at the center of the laser spot was monitored in real time using a hollow glass optical fiber-based two-color infrared thermometer. The surface temperature was limited by either a room-temperature saline drip or direct feedback control of the laser using a mechanical shutter to alternately pass and block the laser. Acute patency was evaluated either visually (leak/no leak) or by in vivo burst pressure measurements. Biochemical assays were performed to investigate the possible laser-induced formation or destruction of enzymatically mediated covalent crosslinks between collagen molecules. Viable welds were created both with and without the use of feedback control. Tissues maintained at 50 C using feedback control had an elevated crosslink count compared to controls, while those irradiated without feedback control experienced a decrease. Differences between the volumetric heating associated with open and closed loop protocols may account for the different effects on collagen crosslinks. Covalent mechanisms may play a role in argon laser vascular fusion.

  3. Hyperglycemia and hyperlipidemia blunts the Insulin-Inpp5f negative feedback loop in the diabetic heart

    PubMed Central

    Bai, Danna; Zhang, Yajun; Shen, Mingzhi; Sun, Yongfeng; Xia, Qing; Zhang, Yingmei; Liu, Xuedong; Wang, Haichang; Yuan, Lijun

    2016-01-01

    The leading cause of death in diabetic patients is diabetic cardiomyopathy, in which alteration of Akt signal plays an important role. Inpp5f is recently found to be a negative regulator of Akt signaling, while its expression and function in diabetic heart is largely unknown. In this study, we found that in both the streptozotocin (STZ) and high fat diet (HFD) induced diabetic mouse models, Inpp5f expression was coordinately regulated by insulin, blood glucose and lipid levels. Increased Inpp5f was inversely correlated with the cardiac function. Further studies revealed that Insulin transcriptionally activated Inpp5f in an Sp1 dependent manner, and increased Inpp5f in turn reduced the phosphorylation of Akt, forming a negative feedback loop. The negative feedback plays a protective role under diabetic condition. However, high blood glucose and lipid, which are characteristics of uncontrolled diabetes and type 2 diabetes, increased Inpp5f expression through activation of NF-κB, blunts the protective feedback. Thus, our study has revealed that Inpp5f provides as a negative feedback regulator of insulin signaling and downregulation of Inpp5f in diabetes is cardioprotective. Increased Inpp5f by hyperglycemia and hyperlipidemia is an important mediator of diabetic cardiomyopathy and is a promising therapeutic target for the disease. PMID:26908121

  4. In-vivo argon laser vascular welding using thermal feedback: open- and closed-loop patency and collagen crosslinking

    NASA Astrophysics Data System (ADS)

    Small, Ward, IV; Celliers, Peter M.; Kopchok, George E.; Reiser, Karen M.; Heredia, Nicholas J.; Maitland, Duncan J.; Eder, David C.; London, Richard A.; Heilbron, Mauricio; Hussain, Farabi; White, Rodney A.; Da Silva, Luiz B.; Matthews, Dennis L.

    1997-05-01

    An in vivo study of vascular welding with a fiber-delivered argon laser was conducted using a canine model. Longitudinal arteriotomies and venotomies were treated on femoral vein and artery. Laser energy was delivered to the vessel wall via a 400 micrometer optical fiber. The surface temperature at the center of the laser spot was monitored in real time using a hollow glass optical fiber-based two-color infrared thermometer. The surface temperature was limited by either a room-temperature saline drip or direct feedback control of the laser using a mechanical shutter to alternately pass and block the laser. Acute patency was evaluated either visually (leak/no leak) or by in vivo burst pressure measurements. Biochemical assays were performed to investigate the possible laser-induced formation or destruction of enzymatically mediated covalent crosslinks between collagen molecules. Viable welds were created both with and without the use of feedback control. Tissues maintained at 50 degrees Celsius using feedback control had an elevated crosslink count compared to controls, while those irradiated without feedback control experienced a decrease. Differences between the volumetric heating associated with open and closed loop protocols may account for the different effects on collagen crosslinks. Covalent mechanisms may play a role in argon laser vascular fusion.

  5. Closed-loop, non-linear feedback control simulations of beam-driven field-reversed configurations (FRCs)

    NASA Astrophysics Data System (ADS)

    Rath, N.; Onofri, M.; Barnes, D.; Romero, J.; the TAE Team

    2015-11-01

    The C-2U device has recently demonstrated sustainment of an advanced, beam-driven FRC over time scales longer than the characteristic times for confinement, fast ion slow-down, and wall current decay. In anticipation of further advances in plasma lifetime, we are developing feedback control techniques for major FRC parameters and resistive instabilities. The LamyRidge code solves the time-dependent extended MHD equations in axisymmetric geometry. In the Q2D code, LamyRidge is combined with a 3-D kinetic code that tracks fast ions and runs in parallel with LamyRidge. Periodically, the background fields in the kinetic code are updated from the MHD simulation and the averaged fast particle distribution is integrated into the fluid equations. Recently, we have added the capability to run Q2D simulations as subordinate processes in Simulink, giving us the ability to run non-linear, closed-loop simulations using control algorithms developed in Simulink. The same Simulink models can be exported to real-time targets (CPU or FPGA) to perform feedback control in experiments. We present closed-loop simulations of beam-driven FRCs under magnetically-actuated feedback control. Results for positionally unstable FRCs are compared with the predictions of a linearized rigid-plasma model. Plasmas predicted to be passively stabilized by the linear model are found to exhibit Alfvenic growth in several cases. Feedback gains predicted to be stabilizing in the linear model are generally found to be insufficient in non-linear simulations, and vice versa. Control of separatrix geometry is demonstrated.

  6. Parallel feedback loops control the basal activity of the HOG MAPK signaling cascade.

    PubMed

    Sharifian, Hoda; Lampert, Fabienne; Stojanovski, Klement; Regot, Sergi; Vaga, Stefania; Buser, Raymond; Lee, Sung Sik; Koeppl, Heinz; Posas, Francesc; Pelet, Serge; Peter, Matthias

    2015-04-01

    Tight regulation of the MAP kinase Hog1 is crucial for survival under changing osmotic conditions. Interestingly, we found that Hog1 phosphorylates multiple upstream components, implying feedback regulation within the signaling cascade. Taking advantage of an unexpected link between glucose availability and Hog1 activity, we used quantitative single cell measurements and computational modeling to unravel feedback regulation operating in addition to the well-known adaptation feedback triggered by glycerol accumulation. Indeed, we found that Hog1 phosphorylates its activating kinase Ssk2 on several sites, and cells expressing a non-phosphorylatable Ssk2 mutant are partially defective for feedback regulation and proper control of basal Hog1 activity. Together, our data suggest that Hog1 activity is controlled by intertwined regulatory mechanisms operating with varying kinetics, which together tune the Hog1 response to balance basal Hog1 activity and its steady-state level after adaptation to high osmolarity. PMID:25734609

  7. Boosting the voltage gain of graphene FETs through a differential amplifier scheme with positive feedback

    NASA Astrophysics Data System (ADS)

    Grassi, R.; Gnudi, A.; Di Lecce, V.; Gnani, E.; Reggiani, S.; Baccarani, G.

    2014-10-01

    We study a possible circuit solution to overcome the problem of low voltage gain of short-channel graphene FETs. The circuit consists of a fully differential amplifier with a load made of a cross-coupled transistor pair. Starting from the device characteristics obtained from self-consistent ballistic quantum transport simulations, we explore the circuit parameter space and evaluate the amplifier performance in terms of dc voltage gain and voltage gain bandwidth. We show that the dc gain can be effectively improved by the negative differential resistance provided by the cross-coupled pair. Contact resistance is the main obstacle to achieving gain bandwidth products in the terahertz range. Limitations of the proposed amplifier are identified with its poor linearity and relatively large Miller capacitance.

  8. Investigation, development and application of optimal output feedback theory. Volume 2: Development of an optimal, limited state feedback outer-loop digital flight control system for 3-D terminal area operation

    NASA Technical Reports Server (NTRS)

    Broussard, J. R.; Halyo, N.

    1984-01-01

    This report contains the development of a digital outer-loop three dimensional radio navigation (3-D RNAV) flight control system for a small commercial jet transport. The outer-loop control system is designed using optimal stochastic limited state feedback techniques. Options investigated using the optimal limited state feedback approach include integrated versus hierarchical control loop designs, 20 samples per second versus 5 samples per second outer-loop operation and alternative Type 1 integration command errors. Command generator tracking techniques used in the digital control design enable the jet transport to automatically track arbitrary curved flight paths generated by waypoints. The performance of the design is demonstrated using detailed nonlinear aircraft simulations in the terminal area, frequency domain multi-input sigma plots, frequency domain single-input Bode plots and closed-loop poles. The response of the system to a severe wind shear during a landing approach is also presented.

  9. Noncanonical Activin A Signaling in PC12 Cells: A Self-Limiting Feedback Loop.

    PubMed

    Wang, Jiao-Qi; Liang, Wen-Zhao; Cui, Yang; He, Jin-Ting; Liu, Hong-Yu; Wang, Yue; Xue, Long-Xing; Ji, Qiu-Ye; Shi, Wei; Shao, Yan-Kun; Mang, Jing; Xu, Zhong-Xin

    2016-05-01

    Activin A (Act A), a member of transforming growth factor-β superfamily, plays a neuroprotective role in multiple neurological diseases through Act A/Smads signal activation. Traditionally, the up-regulation of Act A gene and extracellular Act A accumulation show the signal activation as a linear pathway. However, one of our discoveries indicated that Act A could lead a loop signaling in ischemic injury. To clarify the characteristic of this loop signaling in a non-pathological state, we up-regulated the expression of Act A, monitored extracellular Act A accumulation and examined the activity of Act A signaling, which was quantified by the expression of phosphorylated Smad3 and the fluorescence intensity of Smad4 in nuclei. The results demonstrated a noncanonical Act A signal loop with self-amplifying property in PC12 cells. Further, it showed self-limiting behavior due to temporary activation and spontaneous attenuation. This periodic behavior of Act A signal loop was found to be regulated by the level of Smad anchor for receptor activation (SARA). Moreover, increased activity of Act A signal loop could promote PC12 cell proliferation and enhance the survival rate of cells to Oxygen-Glucose Deprivation. These practical discoveries will bring new insight on the functional outcome of Act A signaling in neurological diseases by the further understanding: loop signaling. PMID:26721511

  10. Chk1 Activation Protects Rad9A from Degradation as Part of a Positive Feedback Loop during Checkpoint Signalling

    PubMed Central

    Osorio-Zambrano, William F.; Davey, Scott

    2015-01-01

    Phosphorylation of Rad9A at S387 is critical for establishing a physical interaction with TopBP1, and to downstream activation of Chk1 for checkpoint activation. We have previously demonstrated a phosphorylation of Rad9A that occurs at late time points in cells exposed to genotoxic agents, which is eliminated by either Rad9A overexpression, or conversion of S387 to a non-phosphorylatable analogue. Based on this, we hypothesized that this late Rad9A phosphorylation is part of a feedback loop regulating the checkpoint. Here, we show that Rad9A is hyperphosphorylated and accumulates in cells exposed to bleomycin. Following the removal of bleomycin, Rad9A is polyubiquitinated, and Rad9A protein levels drop, indicating an active degradation process for Rad9A. Chk1 inhibition by UCN-01 or siRNA reduces Rad9A levels in cells synchronized in S-phase or exposed to DNA damage, indicating that Chk1 activation is required for Rad9A stabilization in S-phase and during checkpoint activation. Together, these results demonstrate a positive feedback loop involving Rad9A-dependend activation of Chk1, coupled with Chk1-dependent stabilization of Rad9A that is critical for checkpoint regulation. PMID:26658951

  11. GLP-1 Cleavage Product Reverses Persistent ROS Generation After Transient Hyperglycemia by Disrupting an ROS-Generating Feedback Loop.

    PubMed

    Giacco, Ferdinando; Du, Xueliang; Carrat, Anna; Gerfen, Gary J; D'Apolito, Maria; Giardino, Ida; Rasola, Andrea; Marin, Oriano; Divakaruni, Ajit S; Murphy, Anne N; Shah, Manasi S; Brownlee, Michael

    2015-09-01

    The assumption underlying current diabetes treatment is that lowering the level of time-averaged glucose concentrations, measured as HbA1c, prevents microvascular complications. However, 89% of variation in risk of retinopathy, microalbuminuria, or albuminuria is due to elements of glycemia not captured by mean HbA1c values. We show that transient exposure to high glucose activates a multicomponent feedback loop that causes a stable left shift of the glucose concentration-reactive oxygen species (ROS) dose-response curve. Feedback loop disruption by the GLP-1 cleavage product GLP-1(9-36)(amide) reverses the persistent left shift, thereby normalizing persistent overproduction of ROS and its pathophysiologic consequences. These data suggest that hyperglycemic spikes high enough to activate persistent ROS production during subsequent periods of normal glycemia but too brief to affect the HbA1c value are a major determinant of the 89% of diabetes complications risk not captured by HbA1c. The phenomenon and mechanism described in this study provide a basis for the development of both new biomarkers to complement HbA1c and novel therapeutic agents, including GLP-1(9-36)(amide), for the prevention and treatment of diabetes complications. PMID:26294429

  12. The LSD1 Family of Histone Demethylases and the Pumilio Posttranscriptional Repressor Function in a Complex Regulatory Feedback Loop

    PubMed Central

    Miles, Wayne O.; Lepesant, Julie M. J.; Bourdeaux, Jessie; Texier, Manuela; Kerenyi, Marc A.; Nakakido, Makoto; Hamamoto, Ryuji; Orkin, Stuart H.; Dyson, Nicholas J.

    2015-01-01

    The lysine (K)-specific demethylase (LSD1) family of histone demethylases regulates chromatin structure and the transcriptional potential of genes. LSD1 is frequently deregulated in tumors, and depletion of LSD1 family members causes developmental defects. Here, we report that reductions in the expression of the Pumilio (PUM) translational repressor complex enhanced phenotypes due to dLsd1 depletion in Drosophila. We show that the PUM complex is a target of LSD1 regulation in fly and mammalian cells and that its expression is inversely correlated with LSD1 levels in human bladder carcinoma. Unexpectedly, we find that PUM posttranscriptionally regulates LSD1 family protein levels in flies and human cells, indicating the existence of feedback loops between the LSD1 family and the PUM complex. Our results highlight a new posttranscriptional mechanism regulating LSD1 activity and suggest that the feedback loop between the LSD1 family and the PUM complex may be functionally important during development and in human malignancies. PMID:26438601

  13. Mutant p53 initiates a feedback loop that involves Egr-1/EGF receptor/ERK in prostate cancer cells.

    PubMed

    Sauer, L; Gitenay, D; Vo, C; Baron, V T

    2010-05-01

    Early growth response-1 (Egr-1) is overexpressed in human prostate tumors and contributes to cancer progression. On the other hand, mutation of p53 is associated with advanced prostate cancer, as well as with metastasis and hormone independence. This study shows that in prostate cell lines in culture, Egr-1 overexpression correlated with an alteration of p53 activity because of the expression of SV40 large T-antigen or because of a mutation in the TP53 gene. In cells containing altered p53 activity, Egr-1 expression was abolished by pharmacological inhibition or RNAi silencing of p53. Although forced expression of wild-type p53 was not sufficient to trigger Egr-1 transcription, four different mutants of p53 were shown to induce Egr-1. Direct binding of p53 to the EGR1 promoter could not be detected. Instead, Egr-1 transcription was driven by the ERK1/2 pathway, as it was abrogated by specific inhibitors of MEK. Egr-1 increased the transcription of HB-EGF (epidermal growth factor), amphiregulin and epiregulin, resulting in autocrine activation of the EGF receptor (EGFR) and downstream MEK/ERK cascade. Thus, mutant p53 initiates a feedback loop that involves ERK1/2-mediated transactivation of Egr-1, which in turn increases the secretion of EGFR ligands and stimulates the EGFR signaling pathway. Finally, p53 may further regulate this feedback loop by altering the level of EGFR expression. PMID:20190820

  14. A feedback loop between nonsense-mediated decay and the retrogene DUX4 in facioscapulohumeral muscular dystrophy.

    PubMed

    Feng, Qing; Snider, Lauren; Jagannathan, Sujatha; Tawil, Rabi; van der Maarel, Silvère M; Tapscott, Stephen J; Bradley, Robert K

    2015-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a muscular dystrophy caused by inefficient epigenetic repression of the D4Z4 macrosatellite array and somatic expression of the DUX4 retrogene. DUX4 is a double homeobox transcription factor that is normally expressed in the testis and causes apoptosis and FSHD when misexpressed in skeletal muscle. The mechanism(s) of DUX4 toxicity in muscle is incompletely understood. We report that DUX4-triggered proteolytic degradation of UPF1, a central component of the nonsense-mediated decay (NMD) machinery, is associated with profound NMD inhibition, resulting in global accumulation of RNAs normally degraded as NMD substrates. DUX4 mRNA is itself degraded by NMD, such that inhibition of NMD by DUX4 protein stabilizes DUX4 mRNA through a double-negative feedback loop in FSHD muscle cells. This feedback loop illustrates an unexpected mode of autoregulatory behavior of a transcription factor, is consistent with 'bursts' of DUX4 expression in FSHD muscle, and has implications for FSHD pathogenesis. PMID:25564732

  15. Targeting mTOR signaling pathways and related negative feedback loops for the treatment of acute myeloid leukemia

    PubMed Central

    Carneiro, Benedito A; Kaplan, Jason B; Altman, Jessica K; Giles, Francis J; Platanias, Leonidas C

    2015-01-01

    An accumulating understanding of the complex pathogenesis of acute myeloid leukemia (AML) continues to lead to promising therapeutic approaches. Among the key aberrant intracellular signaling pathways involved in AML, the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) axis is of major interest. This axis modulates a wide array of critical cellular functions, including proliferation, metabolism, and survival. Pharmacologic inhibitors of components of this pathway have been developed over the past decade, but none has an established role in the treatment of AML. This review will discuss the preclinical data and clinical results driving ongoing attempts to exploit the PI3K/AKT/mTOR pathway in patients with AML and address issues related to negative feedback loops that account for leukemic cell survival. Targeting the PI3K/AKT/mTOR pathway is of high interest for the treatment of AML, but combination therapies with other targeted agents may be needed to block negative feedback loops in leukemia cells. PMID:25801978

  16. The LSD1 Family of Histone Demethylases and the Pumilio Posttranscriptional Repressor Function in a Complex Regulatory Feedback Loop.

    PubMed

    Miles, Wayne O; Lepesant, Julie M J; Bourdeaux, Jessie; Texier, Manuela; Kerenyi, Marc A; Nakakido, Makoto; Hamamoto, Ryuji; Orkin, Stuart H; Dyson, Nicholas J; Di Stefano, Luisa

    2015-12-01

    The lysine (K)-specific demethylase (LSD1) family of histone demethylases regulates chromatin structure and the transcriptional potential of genes. LSD1 is frequently deregulated in tumors, and depletion of LSD1 family members causes developmental defects. Here, we report that reductions in the expression of the Pumilio (PUM) translational repressor complex enhanced phenotypes due to dLsd1 depletion in Drosophila. We show that the PUM complex is a target of LSD1 regulation in fly and mammalian cells and that its expression is inversely correlated with LSD1 levels in human bladder carcinoma. Unexpectedly, we find that PUM posttranscriptionally regulates LSD1 family protein levels in flies and human cells, indicating the existence of feedback loops between the LSD1 family and the PUM complex. Our results highlight a new posttranscriptional mechanism regulating LSD1 activity and suggest that the feedback loop between the LSD1 family and the PUM complex may be functionally important during development and in human malignancies. PMID:26438601

  17. The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors

    PubMed Central

    Srinivasan, R. Sathish; Escobedo, Noelia; Yang, Ying; Interiano, Ashley; Dillard, Miriam E.; Finkelstein, David; Mukatira, Suraj; Gil, Hyea Jin; Nurmi, Harri; Alitalo, Kari

    2014-01-01

    The mammalian lymphatic vasculature is important for returning fluids from the extracellular tissue milieu back to the blood circulation. We showed previously that Prox1 dosage is important for the development of the mammalian lymphatic vasculature. The lack of Prox1 activity results in the complete absence of lymphatic endothelial cells (LECs). In Prox1 heterozygous embryos, the number of LECs is reduced because of a decrease in the progenitor pool in the cardinal vein. This reduction is caused by some progenitor cells being unable to maintain Prox1 expression. In this study, we identified Vegfr3, the cognate receptor of the lymphangiogenic growth factor Vegfc, as a dosage-dependent, direct in vivo target of Prox1. Using various mouse models, we also determined that Vegfr3 regulates Prox1 by establishing a feedback loop necessary to maintain the identity of LEC progenitors and that Vegfc-mediated activation of Vegfr3 signaling is necessary to maintain Prox1 expression in LEC progenitors. We propose that this feedback loop is the main sensing mechanism controlling the number of LEC progenitors and, as a consequence, the number of budding LECs that will form the embryonic lymphatic vasculature. PMID:25274728

  18. The Y-located gonadoblastoma gene TSPY amplifies its own expression through a positive feedback loop in prostate cancer cells

    SciTech Connect

    Kido, Tatsuo; Lau, Yun-Fai Chris

    2014-03-28

    Highlights: • Y-encoded proto-oncoprotein TSPY amplifies its expression level via a positive feedback loop. • TSPY binds to the chromatin/DNA at exon 1 of TSPY gene. • TSPY enhances the gene expression in a TSPY exon 1 sequence dependent manner. • The conserved SET/NAP-domain is essential for TSPY transactivation. • Insights on probable mechanisms on TSPY exacerbation on cancer development in men. - Abstract: The testis-specific protein Y-encoded (TSPY) is a repetitive gene located on the gonadoblastoma region of the Y chromosome, and has been considered to be the putative gene for this oncogenic locus on the male-only chromosome. It is expressed in spermatogonial cells and spermatocytes in normal human testis, but abundantly in gonadoblastoma, testicular germ cell tumors and a variety of somatic cancers, including melanoma, hepatocellular carcinoma and prostate cancer. Various studies suggest that TSPY accelerates cell proliferation and growth, and promotes tumorigenesis. In this report, we show that TSPY could bind directly to the chromatin/DNA at exon 1 of its own gene, and greatly enhance the transcriptional activities of the endogenous gene in the LNCaP prostate cancer cells. Domain mapping analyses of TSPY have localized the critical and sufficient domain to the SET/NAP-domain. These results suggest that TSPY could efficiently amplify its expression and oncogenic functions through a positive feedback loop, and contribute to the overall tumorigenic processes when it is expressed in various human cancers.

  19. Effect of Abscisic Acid on the Gain of the Feedback Loop Involving Carbon Dioxide and Stomata 1

    PubMed Central

    Dubbe, Dean R.; Farquhar, Graham D.; Raschke, Klaus

    1978-01-01

    Gains of the feedback loops involving intercellular CO2 concentration on one hand, and CO2 assimilation and stomata on the other (= assimilation loop with gain [GA] and conductance loop with gain [Gg]) were determined in detached leaves of Amaranthus powelli S. Wats., Avena sativa L., Gossypium hirsutum L., Xanthium strumarium L., and Zea mays in the absence and presence of 10−5 m (±) abscisic acid (ABA) in the transpiration stream. Determinations were made for an ambient CO2 concentration of 300 microliters per liter. In the absence of ABA, stomata were insensitive to CO2 (Gg between 0.00 and −0.02) in A. sativa, G. hirsutum, and X. strumarium, sensitive in A powelli (Gg = −0.46), and very sensitive in Z. mays (Gg = −3.6). Addition of ABA increased the absolute values of the gain of the conductance loop in A. powelli (Gg = −2.0), G. hirsutum (Gg = −0.31), and X. strumarium (Gg = −1.14). Stomata closed completely in A. sativa. In Z. mays, Gg decreased after application of ABA to a value of −0.86, but stomatal sensitivity to CO2 increased for intercellular CO2 concentrations < 100 microliters per liter. The gain of the assimilation loop increased after application of ABA in all cases, from values between 0.0 (A. powelli) and −0.21 (Z. mays) in the absence of ABA to values between −0.19 (A. powelli) and −0.43 (Z. mays) in the presence of ABA. In none of the species examined did ABA affect the photosynthetic capacity of the leaves. The application of ABA caused stomatal narrowing which affected transpiration more than the assimilation of CO2. In the case of A. powelli the transpiration ratio decreased without a concomitant reduction of the assimilation rate. PMID:16660528

  20. Failure of prolactin short loop feedback mechanism to operate in old as compared to young female rats.

    PubMed

    Sarkar, D K; Miki, N; Meites, J

    1983-10-01

    The short loop feedback effect of PRL was studied in young (4-5 months of age) and old (24-26 months of age) ovariectomized rats after a single iv injection of bovine PRL (bPRL, 500 micrograms/100 g BW) or BSA (500 micrograms/100 g BW). Blood samples were collected via intraatrial cannula every 20 min for assay of PRL. Plasma PRL levels in both young and old ovariectomized rats were pulsatile in nature, and showed approximately one PRL pulse per hour. The magnitude of the PRL peaks and concentrations of plasma PRL, but not the number of PRL peaks, were significantly greater in the old than in the young rats. The effect of bPRL on in situ PRL release was studied after verifying that bPRL does not cross-react with rat PRL RIA, but does significantly increase the release of [3H] dopamine from the median eminence in vitro. This latter effect was dose dependent. In young rats, a single injection of bPRL minimally reduced the concentration of plasma PRL between 100 min and 5 h, but by 22-25 h it decreased plasma PRL to approximately one third of preinjection levels. The magnitude of the PRL pulses, but not the pulse frequency was significantly reduced after administration of bPRL treatment to young rats. Treatment with BSA did not alter the concentration of plasma PRL or the magnitude and frequency of the PRL pulses in young rats. In old rats, plasma PRL concentrations and the frequency and magnitude of the PRL pulses were not significantly decreased after injection of either bPRL or BSA. Thus, the feedback inhibition of PRL on PRL release may not be operative in old rats. The loss of the short loop feedback inhibition of PRL is believed to be due to the reduction in hypothalamic dopaminergic activity previously reported by our and other laboratories in old rats. PMID:6617580

  1. Construction and Modelling of an Inducible Positive Feedback Loop Stably Integrated in a Mammalian Cell-Line

    PubMed Central

    Siciliano, Velia; Fracassi, Chiara; Garzilli, Immacolata; Moretti, Maria Nicoletta; di Bernardo, Diego

    2011-01-01

    Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL) by generating a clonal population of mammalian cells (CHO) carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA), whose expression is regulated by a tTA responsive promoter (CMV-TET), thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP), thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL), by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off), and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the “switch off” times, as comparared to the nonautoregulatated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour. PMID:21765813

  2. Statistics of resonance fluorescence of a pair of atoms in a feedback loop

    SciTech Connect

    Tomilin, V. A. Il'ichev, L. V.

    2013-02-15

    The statistics of photoemission events of a pair of closely spaced two-level atoms is calculated in a classical light field whose phase is changed by {pi} after the detection of each spontaneous photon. This statistics is compared with the statistics in the case when the feedback is missing. In both cases, one can observe noticeable antibunching of photons in the range of parameters where no antibunching is observed in a single-atom system. The feedback substantially increases the antibunching. This effect manifests itself more strongly in relatively weak fields and for considerable frequency detunings.

  3. Net Metering and Market Feedback Loops: Exploring the Impact of Retail Rate Design on Distributed PV Deployment

    SciTech Connect

    Darghouth, Naïm R.; Wiser, Ryan; Barbose, Galen; Mills, Andrew

    2015-01-13

    The substantial increase in deployment of customer-sited solar photovoltaics (PV) in the United States has been driven by a combination of steeply declining costs, financing innovations, and supportive policies. Among those supportive policies is net metering, which in most states effectively allows customers to receive compensation for distributed PV generation at the full retail electricity price. The current design of retail electricity rates and the presence of net metering have elicited concerns that the possible under-recovery of fixed utility costs from PV system owners may lead to a feedback loop of increasing retail prices that accelerate PV adoption and further rate increases. However, a separate and opposing feedback loop could offset this effect: increased PV deployment may lead to a shift in the timing of peak-period electricity prices that could reduce the bill savings received under net metering where time-varying retail electricity rates are used, thereby dampening further PV adoption. In this paper, we examine the impacts of these two competing feedback dynamics on U.S. distributed PV deployment through 2050 for both residential and commercial customers, across states. Our results indicate that, at the aggregate national level, the two feedback effects nearly offset one another and therefore produce a modest net effect, although their magnitude and direction vary by customer segment and by state. We also model aggregate PV deployment trends under various rate designs and net-metering rules, accounting for feedback dynamics. Our results demonstrate that future adoption of distributed PV is highly sensitive to retail rate structures. Whereas flat, time-invariant rates with net metering lead to higher aggregate national deployment levels than the current mix of rate structures (+5% in 2050), rate structures with higher monthly fixed customer charges or PV compensation at levels lower than the full retail rate can dramatically erode aggregate customer adoption of PV (from -14% to -61%, depending on the design). Moving towards time-varying rates, on the other hand, may accelerate near- and medium-term deployment (through 2030), but is found to slow adoption in the longer term (-22% in 2050).

  4. The effect of sensory feedback on crayfish posture and locomotion: II. Neuromechanical simulation of closing the loop.

    PubMed

    Bacqué-Cazenave, Julien; Chung, Bryce; Cofer, David W; Cattaert, Daniel; Edwards, Donald H

    2015-03-15

    Neuromechanical simulation was used to determine whether proposed thoracic circuit mechanisms for the control of leg elevation and depression in crayfish could account for the responses of an experimental hybrid neuromechanical preparation when the proprioceptive feedback loop was open and closed. The hybrid neuromechanical preparation consisted of a computational model of the fifth crayfish leg driven in real time by the experimentally recorded activity of the levator and depressor (Lev/Dep) nerves of an in vitro preparation of the crayfish thoracic nerve cord. Up and down movements of the model leg evoked by motor nerve activity released and stretched the model coxobasal chordotonal organ (CBCO); variations in the CBCO length were used to drive identical variations in the length of the live CBCO in the in vitro preparation. CBCO afferent responses provided proprioceptive feedback to affect the thoracic motor output. Experiments performed with this hybrid neuromechanical preparation were simulated with a neuromechanical model in which a computational circuit model represented the relevant thoracic circuitry. Model simulations were able to reproduce the hybrid neuromechanical experimental results to show that proposed circuit mechanisms with sensory feedback could account for resistance reflexes displayed in the quiescent state and for reflex reversal and spontaneous Lev/Dep bursting seen in the active state. PMID:25552643

  5. Closed-loop torque feedback for a universal field-oriented controller

    DOEpatents

    De Doncker, Rik W. A. A.; King, Robert D.; Sanza, Peter C.; Haefner, Kenneth B.

    1992-01-01

    A torque feedback system is employed in a universal field-oriented (UFO) controller to tune a torque-producing current command and a slip frequency command in order to achieve robust torque control of an induction machine even in the event of current regulator errors and during transitions between pulse width modulated (PWM) and square wave modes of operation.

  6. Chaotic Feedback Loops within Decision Making Groups: Towards an Integration of Chaos Theory and Cybernetics.

    ERIC Educational Resources Information Center

    Keaten, James A.

    This paper offers a model that integrates chaos theory and cybernetics, which can be used to describe the structure of decision making within small groups. The paper begins with an overview of cybernetics and chaos. Definitional characteristics of cybernetics are reviewed along with salient constructs, such as goal-seeking, feedback, feedback…

  7. DEPENDENCE OF STEM CELL FATE IN ARABIDOPSIS ON A FEEDBACK LOOP REGULATED BY CLV3 ACTIVITY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fate of stem cells in plant meristems is governed by directional signalling systems that are regulated by negative feedback. In Arabidopsis, the CLAVATA (CLV) genes encode the essential components of a negative, stem cell restricting pathway. We have used transgenic plants over-expressing CLV3 t...

  8. Closed-loop torque feedback for a universal field-oriented controller

    DOEpatents

    De Doncker, R.W.A.A.; King, R.D.; Sanza, P.C.; Haefner, K.B.

    1992-11-24

    A torque feedback system is employed in a universal field-oriented (UFO) controller to tune a torque-producing current command and a slip frequency command in order to achieve robust torque control of an induction machine even in the event of current regulator errors and during transitions between pulse width modulated (PWM) and square wave modes of operation. 1 figure.

  9. Bidirectional neural interface: Closed-loop feedback control for hybrid neural systems.

    PubMed

    Zane Chou; Lim, Jeffrey; Brown, Sophie; Keller, Melissa; Bugbee, Joseph; Broccard, Frederic D; Khraiche, Massoud L; Silva, Gabriel A; Cauwenberghs, Gert

    2015-08-01

    Closed-loop neural prostheses enable bidirectional communication between the biological and artificial components of a hybrid system. However, a major challenge in this field is the limited understanding of how these components, the two separate neural networks, interact with each other. In this paper, we propose an in vitro model of a closed-loop system that allows for easy experimental testing and modification of both biological and artificial network parameters. The interface closes the system loop in real time by stimulating each network based on recorded activity of the other network, within preset parameters. As a proof of concept we demonstrate that the bidirectional interface is able to establish and control network properties, such as synchrony, in a hybrid system of two neural networks more significantly more effectively than the same system without the interface or with unidirectional alternatives. This success holds promise for the application of closed-loop systems in neural prostheses, brain-machine interfaces, and drug testing. PMID:26737158

  10. Temperature control feedback loops for the linac upgrade side coupled cavities at Fermilab

    SciTech Connect

    Crisp, J.

    1990-10-25

    The linac upgrade project at Fermilab will replace the last 4 drift-tube linac tanks with seven side coupled cavity strings. This will increase the beam energy from 200 to 400 MeV at injection into the Booster accelerator. The main objective of the temperature loop is to control the resonant frequency of the cavity strings. A cavity string will constant of 4 sections connected with bridge couplers driven with a 12 MW klystron at 805 MHz. Each section is a side coupled cavity chain consisting of 16 accelerating cells and 15 side coupling cells. For the linac upgrade, 7 full cavity strings will be used. A separate temperature control system is planned for each of the 28 accelerating sections, the two transition sections, and the debuncher section. The cavity strings will be tuned to resonance for full power beam loaded conditions. A separate frequency loop is planned that will sample the phase difference between a monitor placed in the end cell of each section and the rf drive. The frequency loop will control the set point for the temperature loop which will be able to maintain the resonant frequency through periods within beam or rf power. The frequency loop will need the intelligence required to determine under what conditions the phase error information is valid and the temperature set point should be adjusted. This paper will discuss some of the reason for temperature control, the implementation, and some of the problems encountered. An appendix contains some useful constants and descriptions of some of the sensor and control elements used. 13 figs.

  11. Cascaded integrator comb filters with smoothly varying coefficients for reduced delay in synchrotron feedback loops

    NASA Astrophysics Data System (ADS)

    Schnase, A.; Nomura, M.; Tamura, F.; Yamamoto, M.; Anami, S.; Ezura, E.; Hara, K.; Ohmori, C.; Takagi, A.; Yoshii, M.

    2005-12-01

    The Rapid Cycling Synchrotron (RCS) of the J-PARC complex in Tokai, Japan, is designed to accelerate a high intensity proton beam from 181 MeV, and later 400 MeV to 3 GeV in 20 ms within the 40 ms machine cycle. The beam power up to 1 MW demands a stable beam control to avoid excessive losses and activation of the accelerator chain. The fully digital control system is based on quadrature modulation and demodulation. In the amplitude control loops standard FIR filters separate the harmonics (h=2) and (h=4) after down conversion. For the phase loops at (h=2) and (h=4), intended to damp synchrotron oscillations, the delay in a FIR filter would limit the loop stability. Cascaded integrator comb filters, also called CIC filters, provide a shorter delay because they filter the longitudinal beam signal only where it is necessary. The notches are located at multiples of the revolution frequency of the proton beam. For fixed frequency accelerator applications, digital comb filters with fixed clock frequency are widely used to improve loop stability. For variable frequency accelerator applications, as in a proton synchrotron, where the frequency swing is larger than the notch width, usually the clock frequency of the comb filter is variable and chosen to be an integer multiple of the particle revolution frequency. At J-PARC RCS, the clock frequency has to be fixed. Tracking the frequency would require a variable noninteger number of filter taps. Here we present a filter, based on the weighted output of 2 CIC filters with variable length, and one tap difference. The filter function looks like a CIC with smoothly varying coefficients, where the notches follow the revolution frequency of the proton beam. The delay of this filter is approximately half of the corresponding FIR filter, so that the phase loops have a higher stability margin.

  12. Model-based rational feedback controller design for closed-loop deep brain stimulation of Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Gorzelic, P.; Schiff, S. J.; Sinha, A.

    2013-04-01

    Objective. To explore the use of classical feedback control methods to achieve an improved deep brain stimulation (DBS) algorithm for application to Parkinson's disease (PD). Approach. A computational model of PD dynamics was employed to develop model-based rational feedback controller design. The restoration of thalamocortical relay capabilities to patients suffering from PD is formulated as a feedback control problem with the DBS waveform serving as the control input. Two high-level control strategies are tested: one that is driven by an online estimate of thalamic reliability, and another that acts to eliminate substantial decreases in the inhibition from the globus pallidus interna (GPi) to the thalamus. Control laws inspired by traditional proportional-integral-derivative (PID) methodology are prescribed for each strategy and simulated on this computational model of the basal ganglia network. Main Results. For control based upon thalamic reliability, a strategy of frequency proportional control with proportional bias delivered the optimal control achieved for a given energy expenditure. In comparison, control based upon synaptic inhibitory output from the GPi performed very well in comparison with those of reliability-based control, with considerable further reduction in energy expenditure relative to that of open-loop DBS. The best controller performance was amplitude proportional with derivative control and integral bias, which is full PID control. We demonstrated how optimizing the three components of PID control is feasible in this setting, although the complexity of these optimization functions argues for adaptive methods in implementation. Significance. Our findings point to the potential value of model-based rational design of feedback controllers for Parkinson's disease.

  13. TLR4 signaling promotes a COX-2/PGE2/STAT3 positive feedback loop in hepatocellular carcinoma (HCC) cells

    PubMed Central

    Lin, Ang; Wang, Guan; Zhao, Huajun; Zhang, Yuyi; Han, Qiuju; Zhang, Cai; Tian, Zhigang; Zhang, Jian

    2016-01-01

    ABSTRACT Toll-like receptors (TLRs) can be expressed by tumor cells, and each TLR exhibits different biological functions. Evidences showed the activation of some certain TLRs could promote tumor progression. One of which TLR4 has been found to promote hepatocellular carcinoma (HCC) cells proliferation, but the detailed mechanism is still unknown. In the present study, we verified that TLR4 was functionally expressed on HCC cells, and TLR4 agonist lipopolysaccharide (LPS) could stimulate the proliferation and clone formation of HCC cells. Most importantly, we found a COX-2/PGE2/STAT3 positive feedback loop exists in HCC cells, which could be provoked by TLR4 activation. Consistently, the expression of TLR4, COX-2 and p-STAT3Y705 was positively correlated with each other in liver tumor tissues from patients with primary HCC. Further investigation demonstrated this loop played a dominant role in TLR4-induced HCC cell proliferation and multidrug resistance (MDR) to chemotherapy. Inhibition of TLR4 or COX-2/PGE2/STAT3 loop would attenuate LPS-induced inflammation and proliferation of HCC cells, and enhance the sensitivity of HCC cells to chemotherapeutics in vitro. By using a primary HCC model, we observed COX-2/PGE2/STAT3 loop was significantly blocked in TLR4−/− mice compared to wild type mice, and there was no obvious tumorgenesis sign in TLR4−/− mice. Therefore, these findings provided the precise molecular mechanism of TLR4 signaling pathway involved in HCC progress, and suggested that TLR4 may be a promising target for HCC treatment. PMID:27057441

  14. Development of a fast voltage control method for electrostatic accelerators

    NASA Astrophysics Data System (ADS)

    Lobanov, Nikolai R.; Linardakis, Peter; Tsifakis, Dimitrios

    2014-12-01

    The concept of a novel fast voltage control loop for tandem electrostatic accelerators is described. This control loop utilises high-frequency components of the ion beam current intercepted by the image slits to generate a correction voltage that is applied to the first few gaps of the low- and high-energy acceleration tubes adjoining the high voltage terminal. New techniques for the direct measurement of the transfer function of an ultra-high impedance structure, such as an electrostatic accelerator, have been developed. For the first time, the transfer function for the fast feedback loop has been measured directly. Slow voltage variations are stabilised with common corona control loop and the relationship between transfer functions for the slow and new fast control loops required for optimum operation is discussed. The main source of terminal voltage instabilities, which are due to variation of the charging current caused by mechanical oscillations of charging chains, has been analysed.

  15. Stabilization of polymer electrolyte fuel cell voltage with reduced-order Lyapunov exponent feedback and corrective pressure perturbations

    NASA Astrophysics Data System (ADS)

    Burkholder, Michael B.; Litster, Shawn

    2015-02-01

    Polymer electrolyte fuel cell (PEFC) system efficiency can be decreased by instabilities resulting from the accumulation of water in the cathode as well as by excessive air delivery parasitic loads used to prevent liquid water accumulation. In this work, we present a new instability detection diagnostic tailored for the nonlinear and chaotic dynamics of PEFC operation with multi-phase flow in the gas channels. The instability statistic, the Lyapunov exponent of the reduced-order voltage return map, ?, is a measure of the exponential rate of divergence in the dynamic voltage signal measured from the fuel cell. A key advantage of this statistic for embedded control is that it is a self-referencing measure of the system stability for feedback and is not based on an a priori performance threshold. Our experiments demonstrate that the Lyapunov exponent statistic provides a warning typically 100 s in advance of significant power loss. Using this statistic as a control diagnostic, a new control scheme that detects PEFC instability in real time and mitigates it with pressure perturbations was applied experimentally to several fuel cell systems, including one that simulates stack operation. Our control scheme resulted in increased PEFC power, decreased cathode flooding leading to a lower parasitic load for air delivery, and stable PEFC performance.

  16. Periodic solutions of piecewise affine gene network models with non uniform decay rates: the case of a negative feedback loop.

    PubMed

    Farcot, Etienne; Gouzé, Jean-Luc

    2009-12-01

    This paper concerns periodic solutions of a class of equations that model gene regulatory networks. Unlike the vast majority of previous studies, it is not assumed that all decay rates are identical. To handle this more general situation, we rely on monotonicity properties of these systems. Under an alternative assumption, it is shown that a classical fixed point theorem for monotone, concave operators can be applied to these systems. The required assumption is expressed in geometrical terms as an alignment condition on so-called focal points. As an application, we show the existence and uniqueness of a stable periodic orbit for negative feedback loop systems in dimension 3 or more, and of a unique stable equilibrium point in dimension 2. This extends a theorem of Snoussi, which showed the existence of these orbits only. PMID:19838808

  17. Phospholipase D1 drives a positive feedback loop to reinforce the Wnt/beta-catenin/TCF signaling axis.

    PubMed

    Kang, Dong Woo; Lee, Soung-Hoon; Yoon, Jeong Whan; Park, Won-Sang; Choi, Kang-Yell; Min, Do Sik

    2010-05-15

    Activation of the Wnt signaling pathway occurs frequently in human cancers, but an understanding of the targets and regulation of this important pathway remains incomplete. In this study, we report that phospholipase D (PLD), a cell survival mediator that is upregulated in cancer, is an important target of the Wnt signaling pathway that functions in a positive feedback loop to reinforce pathway output. PLD1 expression and activity was enhanced by treatment with Wnt3a and glycogen synthase kinase-3 inhibitors, and the Wnt pathway-regulated transcription factors beta-catenin and TCF-4 were required for this effect. Three functional TCF-4-binding sites were identified within the PLD1 promoter. Interestingly, suppressing PLD1 blocked the ability of beta-catenin to transcriptionally activate PLD1 and other Wnt target genes by preventing beta-catenin/TCF-4 complex formation. Conversely, tactics to elevate intracellular levels of phosphatidic acid, the product of PLD1 enzyme activity, enhanced beta-catenin/TCF-4 complex formation as well as beta-catenin-dependent TCF transcriptional activity. In cell-based assays, PLD1 was necessary for the anchorage-independent growth driven by Wnt/beta-catenin signaling, whereas beta-catenin/TCF-4 was necessary for the anchorage-independent growth driven by PLD1 activation. Taken together, our findings define a function for PLD1 in a positive feedback loop of Wnt/beta-catenin/TCF-4 signaling that provides new mechanistic insights into cancer, with implications of novel strategies to disrupt Wnt signaling in cancer. PMID:20442281

  18. New numerical methods for open-loop and feedback solutions to dynamic optimization problems

    NASA Astrophysics Data System (ADS)

    Ghosh, Pradipto

    The topic of the first part of this research is trajectory optimization of dynamical systems via computational swarm intelligence. Particle swarm optimization is a nature-inspired heuristic search method that relies on a group of potential solutions to explore the fitness landscape. Conceptually, each particle in the swarm uses its own memory as well as the knowledge accumulated by the entire swarm to iteratively converge on an optimal or near-optimal solution. It is relatively straightforward to implement and unlike gradient-based solvers, does not require an initial guess or continuity in the problem definition. Although particle swarm optimization has been successfully employed in solving static optimization problems, its application in dynamic optimization, as posed in optimal control theory, is still relatively new. In the first half of this thesis particle swarm optimization is used to generate near-optimal solutions to several nontrivial trajectory optimization problems including thrust programming for minimum fuel, multi-burn spacecraft orbit transfer, and computing minimum-time rest-to-rest trajectories for a robotic manipulator. A distinct feature of the particle swarm optimization implementation in this work is the runtime selection of the optimal solution structure. Optimal trajectories are generated by solving instances of constrained nonlinear mixed-integer programming problems with the swarming technique. For each solved optimal programming problem, the particle swarm optimization result is compared with a nearly exact solution found via a direct method using nonlinear programming. Numerical experiments indicate that swarm search can locate solutions to very great accuracy. The second half of this research develops a new extremal-field approach for synthesizing nearly optimal feedback controllers for optimal control and two-player pursuit-evasion games described by general nonlinear differential equations. A notable revelation from this development is that the resulting control law has an algebraic closed-form structure. The proposed method uses an optimal spatial statistical predictor called universal kriging to construct the surrogate model of a feedback controller, which is capable of quickly predicting an optimal control estimate based on current state (and time) information. With universal kriging, an approximation to the optimal feedback map is computed by conceptualizing a set of state-control samples from pre-computed extremals to be a particular realization of a jointly Gaussian spatial process. Feedback policies are computed for a variety of example dynamic optimization problems in order to evaluate the effectiveness of this methodology. This feedback synthesis approach is found to combine good numerical accuracy with low computational overhead, making it a suitable candidate for real-time applications. Particle swarm and universal kriging are combined for a capstone example, a near optimal, near-admissible, full-state feedback control law is computed and tested for the heat-load-limited atmospheric-turn guidance of an aeroassisted transfer vehicle. The performance of this explicit guidance scheme is found to be very promising; initial errors in atmospheric entry due to simulated thruster misfirings are found to be accurately corrected while closely respecting the algebraic state-inequality constraint.

  19. Dependence of stem cell fate in Arabidopsis on a feedback loop regulated by CLV3 activity.

    PubMed

    Brand, U; Fletcher, J C; Hobe, M; Meyerowitz, E M; Simon, R

    2000-07-28

    The fate of stem cells in plant meristems is governed by directional signaling systems that are regulated by negative feedback. In Arabidopsis thaliana, the CLAVATA (CLV) genes encode the essential components of a negative, stem cell-restricting pathway. We used transgenic plants overexpressing CLV3 to show that meristem cell accumulation and fate depends directly on the level of CLV3 activity and that CLV3 signaling occurs exclusively through a CLV1/CLV2 receptor kinase complex. We also demonstrate that the CLV pathway acts by repressing the activity of the transcription factor WUSCHEL, an element of the positive, stem cell-promoting pathway. PMID:10915624

  20. A prototype framework for models of socio-hydrology: identification of key feedback loops and parameterisation approach

    NASA Astrophysics Data System (ADS)

    Elshafei, Y.; Sivapalan, M.; Tonts, M.; Hipsey, M. R.

    2014-06-01

    It is increasingly acknowledged that, in order to sustainably manage global freshwater resources, it is critical that we better understand the nature of human-hydrology interactions at the broader catchment system scale. Yet to date, a generic conceptual framework for building models of catchment systems that include adequate representation of socioeconomic systems - and the dynamic feedbacks between human and natural systems - has remained elusive. In an attempt to work towards such a model, this paper outlines a generic framework for models of socio-hydrology applicable to agricultural catchments, made up of six key components that combine to form the coupled system dynamics: namely, catchment hydrology, population, economics, environment, socioeconomic sensitivity and collective response. The conceptual framework posits two novel constructs: (i) a composite socioeconomic driving variable, termed the Community Sensitivity state variable, which seeks to capture the perceived level of threat to a community's quality of life, and acts as a key link tying together one of the fundamental feedback loops of the coupled system, and (ii) a Behavioural Response variable as the observable feedback mechanism, which reflects land and water management decisions relevant to the hydrological context. The framework makes a further contribution through the introduction of three macro-scale parameters that enable it to normalise for differences in climate, socioeconomic and political gradients across study sites. In this way, the framework provides for both macro-scale contextual parameters, which allow for comparative studies to be undertaken, and catchment-specific conditions, by way of tailored "closure relationships", in order to ensure that site-specific and application-specific contexts of socio-hydrologic problems can be accommodated. To demonstrate how such a framework would be applied, two socio-hydrological case studies, taken from the Australian experience, are presented and the parameterisation approach that would be taken in each case is discussed. Preliminary findings in the case studies lend support to the conceptual theories outlined in the framework. It is envisioned that the application of this framework across study sites and gradients will aid in developing our understanding of the fundamental interactions and feedbacks in such complex human-hydrology systems, and allow hydrologists to improve social-ecological systems modelling through better representation of human feedbacks on hydrological processes.

  1. Perturbations of PIP3 signalling trigger a global remodelling of mRNA landscape and reveal a transcriptional feedback loop

    PubMed Central

    Kiselev, Vladimir Yu.; Juvin, Veronique; Malek, Mouhannad; Luscombe, Nicholas; Hawkins, Phillip; Novère, Nicolas Le; Stephens, Len

    2015-01-01

    PIP3 is synthesized by the Class I PI3Ks and regulates complex cell responses, such as growth and migration. Signals that drive long-term reshaping of cell phenotypes are difficult to resolve because of complex feedback networks that operate over extended times. PIP3-dependent modulation of mRNA accumulation is clearly important in this process but is poorly understood. We have quantified the genome-wide mRNA-landscape of non-transformed, breast epithelium-derived MCF10a cells and its response to acute regulation by EGF, in the presence or absence of a PI3Kα inhibitor, compare it to chronic activation of PI3K signalling by cancer-relevant mutations (isogenic cells expressing an oncomutant PI3Kα allele or lacking the PIP3-phosphatase/tumour-suppressor, PTEN). Our results show that whilst many mRNAs are changed by long-term genetic perturbation of PIP3 signalling (‘butterfly effect’), a much smaller number do so in a coherent fashion with the different PIP3 perturbations. This suggests a subset of more directly regulated mRNAs. We show that mRNAs respond differently to given aspects of PIP3 regulation. Some PIP3-sensitive mRNAs encode PI3K pathway components, thus suggesting a transcriptional feedback loop. We identify the transcription factor binding motifs SRF and PRDM1 as important regulators of PIP3-sensitive mRNAs involved in cell movement. PMID:26464442

  2. The interplay of multiple feedback loops with post-translational kinetics results in bistability of mycobacterial stress response

    PubMed Central

    Tiwari, Abhinav; Balázsi, Gábor; Gennaro, Maria Laura; Igoshin, Oleg A

    2011-01-01

    Bacterial persistence is the phenomenon in which a genetically identical fraction of a bacterial population can survive exposure to stress by reduction or cessation of growth. Persistence in mycobacteria has been recently linked to a stress-response network, consisting of the MprA/MprB two-component system and alternative sigma factor σE. This network contains multiple positive transcriptional feedback loops which may give rise to bistability, making it a good candidate for controlling the mycobacterial persistence switch. To analyze the possibility of bistability, we develop a method that involves decoupling of the network into transcriptional and post-translational interaction modules. As a result we reduce the dimensionality of the dynamical system and independently analyze input–output relations in the two modules to formulate a necessary condition for bistability in terms of their logarithmic gains. We show that neither the positive autoregulation in the MprA/MprB network nor the σE-mediated transcriptional feedback is sufficient to induce bistability in a biochemically realistic parameter range. Nonetheless, inclusion of the post-translational regulation of σE by RseA increases the effective cooperativity of the system, resulting in bistability that is robust to parameter variation. We predict that overexpression or deletion of RseA, the key element controlling the ultrasensitive response, can eliminate bistability. PMID:20733247

  3. Perturbations of PIP3 signalling trigger a global remodelling of mRNA landscape and reveal a transcriptional feedback loop.

    PubMed

    Kiselev, Vladimir Yu; Juvin, Veronique; Malek, Mouhannad; Luscombe, Nicholas; Hawkins, Phillip; Le Novère, Nicolas; Stephens, Len

    2015-11-16

    PIP3 is synthesized by the Class I PI3Ks and regulates complex cell responses, such as growth and migration. Signals that drive long-term reshaping of cell phenotypes are difficult to resolve because of complex feedback networks that operate over extended times. PIP3-dependent modulation of mRNA accumulation is clearly important in this process but is poorly understood. We have quantified the genome-wide mRNA-landscape of non-transformed, breast epithelium-derived MCF10a cells and its response to acute regulation by EGF, in the presence or absence of a PI3Kα inhibitor, compare it to chronic activation of PI3K signalling by cancer-relevant mutations (isogenic cells expressing an oncomutant PI3Kα allele or lacking the PIP3-phosphatase/tumour-suppressor, PTEN). Our results show that whilst many mRNAs are changed by long-term genetic perturbation of PIP3 signalling ('butterfly effect'), a much smaller number do so in a coherent fashion with the different PIP3 perturbations. This suggests a subset of more directly regulated mRNAs. We show that mRNAs respond differently to given aspects of PIP3 regulation. Some PIP3-sensitive mRNAs encode PI3K pathway components, thus suggesting a transcriptional feedback loop. We identify the transcription factor binding motifs SRF and PRDM1 as important regulators of PIP3-sensitive mRNAs involved in cell movement. PMID:26464442

  4. Loop Shaping Control Design for a Supersonic Propulsion System Model Using Quantitative Feedback Theory (QFT) Specifications and Bounds

    NASA Technical Reports Server (NTRS)

    Connolly, Joseph W.; Kopasakis, George

    2010-01-01

    This paper covers the propulsion system component modeling and controls development of an integrated mixed compression inlet and turbojet engine that will be used for an overall vehicle Aero-Propulso-Servo-Elastic (APSE) model. Using previously created nonlinear component-level propulsion system models, a linear integrated propulsion system model and loop shaping control design have been developed. The design includes both inlet normal shock position control and jet engine rotor speed control for a potential supersonic commercial transport. A preliminary investigation of the impacts of the aero-elastic effects on the incoming flow field to the propulsion system are discussed, however, the focus here is on developing a methodology for the propulsion controls design that prevents unstart in the inlet and minimizes the thrust oscillation experienced by the vehicle. Quantitative Feedback Theory (QFT) specifications and bounds, and aspects of classical loop shaping are used in the control design process. Model uncertainty is incorporated in the design to address possible error in the system identification mapping of the nonlinear component models into the integrated linear model.

  5. PYK2 integrates growth factor and cytokine receptors signaling and potentiates breast cancer invasion via a positive feedback loop

    PubMed Central

    Selitrennik, Michael; Lev, Sima

    2015-01-01

    The involvement of ErbB family members in breast cancer progression and metastasis has been demonstrated by many studies. However, the downstream effectors that mediate their migratory and invasive responses have not been fully explored. In this study, we show that the non-receptor tyrosine kinase PYK2 is a key effector of EGFR and HER2 signaling in human breast carcinoma. We found that PYK2 is activated by both EGF and heregulin (HRG) in breast cancer cells, and positively regulates EGF/HRG-induced cell spreading, migration and invasion. PYK2 depletion markedly affects ERK1/2 and STAT3 phosphorylation in response to EGF/HRG as well as to IL8 treatment. Importantly, PYK2 depletion also reduced EGF/HRG-induced MMP9 and IL8 transcription, while IL8 inhibition abrogated EGF-induced MMP9 transcription and attenuated cell invasion. IL8, which is transcriptionally regulated by STAT3 and induces PYK2 activation, prolonged EGF-induced PYK2, STAT3 and ERK1/2 phosphorylation suggesting that IL8 acts through an autocrine loop to reinforce EGF-induced signals. Collectively our studies suggest that PYK2 is a common downstream effector of ErbB and IL8 receptors, and that PYK2 integrates their signaling pathways through a positive feedback loop to potentiate breast cancer invasion. Hence, PYK2 could be a potential therapeutic target for a subset of breast cancer patients. PMID:26084289

  6. A Positive Feedback Loop Involving Gcm1 and Fzd5 Directs Chorionic Branching Morphogenesis in the Placenta

    PubMed Central

    Lu, Jinhua; Zhang, Shuang; Nakano, Haruo; Simmons, David G.; Wang, Shumin; Kong, Shuangbo; Wang, Qiang; Shen, Lianju; Tu, Zhaowei; Wang, Weixiang; Wang, Bingyan; Wang, Hongmei; Wang, Yanling; van Es, Johan H.; Clevers, Hans; Leone, Gustavo; Cross, James C.; Wang, Haibin

    2013-01-01

    Chorioallantoic branching morphogenesis is a key milestone during placental development, creating the large surface area for nutrient and gas exchange, and is therefore critical for the success of term pregnancy. Several Wnt pathway molecules have been shown to regulate placental development. However, it remains largely unknown how Wnt-Frizzled (Fzd) signaling spatiotemporally interacts with other essential regulators, ensuring chorionic branching morphogenesis and angiogenesis during placental development. Employing global and trophoblast-specific Fzd5-null and Gcm1-deficient mouse models, combining trophoblast stem cell lines and tetraploid aggregation assay, we demonstrate here that an amplifying signaling loop between Gcm1 and Fzd5 is essential for normal initiation of branching in the chorionic plate. While Gcm1 upregulates Fzd5 specifically at sites where branching initiates in the basal chorion, this elevated Fzd5 expression via nuclear β-catenin signaling in turn maintains expression of Gcm1. Moreover, we show that Fzd5-mediated signaling induces the disassociation of cell junctions for branching initiation via downregulating ZO-1, claudin 4, and claudin 7 expressions in trophoblast cells at the base of the chorion. In addition, Fzd5-mediated signaling is also important for upregulation of Vegf expression in chorion trophoblast cells. Finally, we demonstrate that Fzd5-Gcm1 signaling cascade is operative during human trophoblast differentiation. These data indicate that Gcm1 and Fzd5 function in an evolutionary conserved positive feedback loop that regulates trophoblast differentiation and sites of chorionic branching morphogenesis. PMID:23610556

  7. A self-enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells.

    PubMed

    Preca, Bogdan-Tiberius; Bajdak, Karolina; Mock, Kerstin; Sundararajan, Vignesh; Pfannstiel, Jessica; Maurer, Jochen; Wellner, Ulrich; Hopt, Ulrich T; Brummer, Tilman; Brabletz, Simone; Brabletz, Thomas; Stemmler, Marc P

    2015-12-01

    Invasion and metastasis of carcinomas are often activated by induction of aberrant epithelial-mesenchymal transition (EMT). This is mainly driven by the transcription factor ZEB1, promoting tumor-initiating capacity correlated with increased expression of the putative stem cell marker CD44. However, the direct link between ZEB1, CD44 and tumourigenesis is still enigmatic. Remarkably, EMT-induced repression of ESRP1 controls alternative splicing of CD44, causing a shift in the expression from the variant CD44v to the standard CD44s isoform. We analyzed whether CD44 and ZEB1 regulate each other and show that ZEB1 controls CD44s splicing by repression of ESRP1 in breast and pancreatic cancer. Intriguingly, CD44s itself activates the expression of ZEB1, resulting in a self-sustaining ZEB1 and CD44s expression. Activation of this novel CD44s-ZEB1 regulatory loop has functional impact on tumor cells, as evident by increased tumor-sphere initiation capacity, drug-resistance and tumor recurrence. In summary, we identified a self-enforcing feedback loop that employs CD44s to activate ZEB1 expression. This renders tumor cell stemness independent of external stimuli, as ZEB1 downregulates ESRP1, further promoting CD44s isoform synthesis. PMID:26077342

  8. A WntD-Dependent Integral Feedback Loop Attenuates Variability in Drosophila Toll Signaling.

    PubMed

    Rahimi, Neta; Averbukh, Inna; Haskel-Ittah, Michal; Degani, Neta; Schejter, Eyal D; Barkai, Naama; Shilo, Ben-Zion

    2016-02-22

    Patterning by morphogen gradients relies on the capacity to generate reproducible distribution profiles. Morphogen spread depends on kinetic parameters, including diffusion and degradation rates, which vary between embryos, raising the question of how variability is controlled. We examined this in the context of Toll-dependent dorsoventral (DV) patterning of the Drosophila embryo. We find that low embryo-to-embryo variability in DV patterning relies on wntD, a Toll-target gene expressed initially at the posterior pole. WntD protein is secreted and disperses in the extracellular milieu, associates with its receptor Frizzled4, and inhibits the Toll pathway by blocking the Toll extracellular domain. Mathematical modeling predicts that WntD accumulates until the Toll gradient narrows to its desired spread, and we support this feedback experimentally. This circuit exemplifies a broadly applicable induction-contraction mechanism, which reduces patterning variability through a restricted morphogen-dependent expression of a secreted diffusible inhibitor. PMID:26906736

  9. Physical Impacts on Ecological Processes Close Ecomorphodynamic Feedback Loops: Recent Examples

    NASA Astrophysics Data System (ADS)

    Murray, A. B.

    2014-12-01

    The effects that vegetation and animals can have on sediment transport and therefore landscape evolution have been recognized and studied for decades. However, the other half of the eco-morphodynamic feedbackthe effects that landscape formation processes have on ecosystem processeshas received focus more recently. Only by studying the couplings in both directions between biological and physical processes simultaneously can we understand the mechanisms important in shaping many landscapes. Here I will illustrate this point with representative examples from recent literature. Although the two-way coupling is essential in landscapes as large and slowly changing as mountain ranges, coastal landscapes provide clear and instructive examples, largely because of the relatively short timescales for landscape/ecosystem evolution in many coastal environments.

  10. Phosphorylation of the Transcription Activator CLOCK Regulates Progression through a ∼24-h Feedback Loop to Influence the Circadian Period in Drosophila*

    PubMed Central

    Mahesh, Guruswamy; Jeong, EunHee; Ng, Fanny S.; Liu, Yixiao; Gunawardhana, Kushan; Houl, Jerry H.; Yildirim, Evrim; Amunugama, Ravi; Jones, Richard; Allen, David L.; Edery, Isaac; Kim, Eun Young; Hardin, Paul E.

    2014-01-01

    Circadian (≅24 h) clocks control daily rhythms in metabolism, physiology, and behavior in animals, plants, and microbes. In Drosophila, these clocks keep circadian time via transcriptional feedback loops in which CLOCK-CYCLE (CLK-CYC) initiates transcription of period (per) and timeless (tim), accumulating levels of PER and TIM proteins feed back to inhibit CLK-CYC, and degradation of PER and TIM allows CLK-CYC to initiate the next cycle of transcription. The timing of key events in this feedback loop are controlled by, or coincide with, rhythms in PER and CLK phosphorylation, where PER and CLK phosphorylation is high during transcriptional repression. PER phosphorylation at specific sites controls its subcellular localization, activity, and stability, but comparatively little is known about the identity and function of CLK phosphorylation sites. Here we identify eight CLK phosphorylation sites via mass spectrometry and determine how phosphorylation at these sites impacts behavioral and molecular rhythms by transgenic rescue of a new Clk null mutant. Eliminating phosphorylation at four of these sites accelerates the feedback loop to shorten the circadian period, whereas loss of CLK phosphorylation at serine 859 increases CLK activity, thereby increasing PER levels and accelerating transcriptional repression. These results demonstrate that CLK phosphorylation influences the circadian period by regulating CLK activity and progression through the feedback loop. PMID:24872414

  11. Autonomous Closed-Loop Tasking, Acquisition, Processing, and Evaluation for Situational Awareness Feedback

    NASA Technical Reports Server (NTRS)

    Frye, Stuart; Mandl, Dan; Cappelaere, Pat

    2016-01-01

    This presentation describes the closed loop satellite autonomy methods used to connect users and the assets on Earth Orbiter- 1 (EO-1) and similar satellites. The base layer is a distributed architecture based on Goddard Mission Services Evolution Concept (GMSEC) thus each asset still under independent control. Situational awareness is provided by a middleware layer through common Application Programmer Interface (API) to GMSEC components developed at GSFC. Users setup their own tasking requests, receive views into immediate past acquisitions in their area of interest, and into future feasibilities for acquisition across all assets. Automated notifications via pubsub feeds are returned to users containing published links to image footprints, algorithm results, and full data sets. Theme-based algorithms are available on-demand for processing.

  12. Closing the User Feedback Loop; Effective and Swift Interface Development at ASF

    NASA Astrophysics Data System (ADS)

    Garron, J.; Simmons, D.; Crevensten, B.

    2011-12-01

    Matching user preferences with advancements in data visualization, access and manipulation methodologies can propel or mire any given data provider. Implementation of open standard technologies increases the rate at which these data providers can deploy new functionality designed to improve the user experience. In this environment of data and technological synthesis, meeting the perceived preferences of the user community for data access improvements must therefore be precise, functional, innovative and finite in scope for quick and successful implementation. ASF receives feedback directly from users, within and without the formalities of the ASF User Working Group, which is catalogued to create a backlog of general and discrete improvements requested for data access. Metrics are collected on hardware and software accessing our systems, data products downloaded, rates of data delivery, and other variables of interest, all of which in turn define requirements of new open source features implemented. Vertex: ASF's Data Portal, powered by the ASF API, is designed and implemented on user feedback, collected metrics and the open standard technology concept, under the mandate of future flexibility. Initial design was focused on the coupling of catalogued user requests and preferences, and geospatial metadata hooks of the ASF Datapool. Secondary iterations enhance user abilities to peruse the contents of the ASF archive as interactive data layers which accept user shapefiles and imported geospatially referenced data, allowing for manipulation and fusion of data within Vertex. These new data interface manifestations, employing open standards technologies, allows for minimized but effective novel interface development, propelling ASF forward in user driven data access enhancements.

  13. Low Power, High Voltage Power Supply with Fast Rise/Fall Time

    NASA Technical Reports Server (NTRS)

    Bearden, Douglas B. (Inventor)

    2007-01-01

    A low power, high voltage power supply system includes a high voltage power supply stage and a preregulator for programming the power supply stage so as to produce an output voltage which is a predetermined fraction of a desired voltage level. The power supply stage includes a high voltage, voltage doubler stage connected to receive the output voltage from the preregulator and for, when activated, providing amplification of the output voltage to the desired voltage level. A first feedback loop is connected between the output of the preregulator and an input of the preregulator while a second feedback loop is connected between the output of the power supply stage and the input of the preregulator.

  14. Low power, high voltage power supply with fast rise/fall time

    NASA Technical Reports Server (NTRS)

    Bearden, Douglas B. (Inventor)

    2007-01-01

    A low power, high voltage power supply system includes a high voltage power supply stage and a preregulator for programming the power supply stage so as to produce an output voltage which is a predetermined fraction of a desired voltage level. The power supply stage includes a high voltage, voltage doubler stage connected to receive the output voltage from the preregulator and for, when activated, providing amplification of the output voltage to the desired voltage level. A first feedback loop is connected between the output of the preregulator and an input of the preregulator while a second feedback loop is connected between the output of the power supply stage and the input of the preregulator.

  15. Analysis of the feedback system in a nonintrusive dynamic flowmeter for measuring Pogo oscillations

    NASA Technical Reports Server (NTRS)

    Chapin, W. G.

    1974-01-01

    Equations were developed which describe the closed loop feedback system operation of a proposed ultrasonic, dynamic, nonintrusive flowmeter whose design is based on a constant phase, voltage controlled frequency feedback concept. These equations are based on linear feedback system theory. The time constant of a low pass filter is taken into account. The equations show that the larger the open loop gain, the smaller the error due to fluctuations in the speed of sound and the smaller the effective time constant.

  16. Improvement of Transient Voltage Responses using an Additional PID-loop on ANFIS-based Composite Controller-SVC (CC-SVC) to Control Chaos and Voltage Collapse in Power Systems

    NASA Astrophysics Data System (ADS)

    Ginarsa, I. Made; Soeprijanto, Adi; Purnomo, Mauridhi Hery; Syafaruddin, Mauridhi Hery; Hiyama, Takashi

    Chaos and voltage collapse are qualitative behaviors in power systems that exist due to lack of reactive power in critical loading. These phenomena are deeply explored using both detailed and approximate models in this paper. The ANFIS-based CC-SVC with an additional PID-loop was proposed to control these problems and to improve transient response of the detailed model. The main function of the PID-loop was to increase the minimum voltage and to decrease the settling time at transient response. The ANFIS-based method was chosen because its computational complexity was more efficient than Mamdani fuzzy logic controller. Therefore the convergence of training processes was more rapidly achieved by the ANFIS-based method. The load voltage was held to the setting value by adjusting the SVC susceptance properly. From the experimental results, the PID-loop was an effective controller which achieved good simulation result for the reactive load, the minimum voltage increased and the settling time decreased at the values of j0.12pu, 0.9435pu and 7.01s, respectively.

  17. MiR-192-Mediated Positive Feedback Loop Controls the Robustness of Stress-Induced p53 Oscillations in Breast Cancer Cells

    PubMed Central

    Bleris, Leonidas; Ma, Lan

    2015-01-01

    The p53 tumor suppressor protein plays a critical role in cellular stress and cancer prevention. A number of post-transcriptional regulators, termed microRNAs, are closely connected with the p53-mediated cellular networks. While the molecular interactions among p53 and microRNAs have emerged, a systems-level understanding of the regulatory mechanism and the role of microRNAs-forming feedback loops with the p53 core remains elusive. Here we have identified from literature that there exist three classes of microRNA-mediated feedback loops revolving around p53, all with the nature of positive feedback coincidentally. To explore the relationship between the cellular performance of p53 with the microRNA feedback pathways, we developed a mathematical model of the core p53-MDM2 module coupled with three microRNA-mediated positive feedback loops involving miR-192, miR-34a, and miR-29a. Simulations and bifurcation analysis in relationship to extrinsic noise reproduce the oscillatory behavior of p53 under DNA damage in single cells, and notably show that specific microRNA abrogation can disrupt the wild-type cellular phenotype when the ubiquitous cell-to-cell variability is taken into account. To assess these in silico results we conducted microRNA-perturbation experiments in MCF7 breast cancer cells. Time-lapse microscopy of cell-population behavior in response to DNA double-strand breaks, together with image classification of single-cell phenotypes across a population, confirmed that the cellular p53 oscillations are compromised after miR-192 perturbations, matching well with the model predictions. Our study via modeling in combination with quantitative experiments provides new evidence on the role of microRNA-mediated positive feedback loops in conferring robustness to the system performance of stress-induced response of p53. PMID:26642352

  18. MiR-192-Mediated Positive Feedback Loop Controls the Robustness of Stress-Induced p53 Oscillations in Breast Cancer Cells.

    PubMed

    Moore, Richard; Ooi, Hsu Kiang; Kang, Taek; Bleris, Leonidas; Ma, Lan

    2015-12-01

    The p53 tumor suppressor protein plays a critical role in cellular stress and cancer prevention. A number of post-transcriptional regulators, termed microRNAs, are closely connected with the p53-mediated cellular networks. While the molecular interactions among p53 and microRNAs have emerged, a systems-level understanding of the regulatory mechanism and the role of microRNAs-forming feedback loops with the p53 core remains elusive. Here we have identified from literature that there exist three classes of microRNA-mediated feedback loops revolving around p53, all with the nature of positive feedback coincidentally. To explore the relationship between the cellular performance of p53 with the microRNA feedback pathways, we developed a mathematical model of the core p53-MDM2 module coupled with three microRNA-mediated positive feedback loops involving miR-192, miR-34a, and miR-29a. Simulations and bifurcation analysis in relationship to extrinsic noise reproduce the oscillatory behavior of p53 under DNA damage in single cells, and notably show that specific microRNA abrogation can disrupt the wild-type cellular phenotype when the ubiquitous cell-to-cell variability is taken into account. To assess these in silico results we conducted microRNA-perturbation experiments in MCF7 breast cancer cells. Time-lapse microscopy of cell-population behavior in response to DNA double-strand breaks, together with image classification of single-cell phenotypes across a population, confirmed that the cellular p53 oscillations are compromised after miR-192 perturbations, matching well with the model predictions. Our study via modeling in combination with quantitative experiments provides new evidence on the role of microRNA-mediated positive feedback loops in conferring robustness to the system performance of stress-induced response of p53. PMID:26642352

  19. Actin-mediated feedback loops in B-cell receptor signaling

    PubMed Central

    Song, Wenxia; Liu, Chaohong; Seeley-Fallen, Margaret K.; Miller, Heather; Ketchum, Christina; Upadhyaya, Arpita

    2013-01-01

    Summary Upon recognizing cognate antigen, B cells mobilize multiple cellular apparatuses to propagate an optimal response. Antigen binding is transduced into cytoplasmic signaling events through B-cell antigen receptor (BCR)-based signalosomes at the B-cell surface. BCR signalosomes are dynamic and transient and are subsequently endocytosed for antigen processing. The function of BCR signalosomes is one of the determining factors for the fate of B cells: clonal expansion, anergy, or apoptosis. Accumulating evidence underscores the importance of the actin cytoskeleton in B-cell activation. We have begun to appreciate the role of actin dynamics in regulating BCR-mediated tonic signaling and the formation of BCR signalosomes. Our recent studies reveal an additional function of the actin cytoskeleton in the downregulation of BCR signaling, consequently contributing to the generation and maintenance of B-cell self-tolerance. In this review, we discuss how actin remodels its organization and dynamics in close coordination with BCR signaling and how actin remodeling in turn amplifies the activation and subsequent downregulation process of BCR signaling, providing vital feedback for optimal BCR activation. PMID:24117821

  20. Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop.

    PubMed

    Löffler, Antje S; Alers, Sebastian; Dieterle, Alexandra M; Keppeler, Hildegard; Franz-Wachtel, Mirita; Kundu, Mondira; Campbell, David G; Wesselborg, Sebastian; Alessi, Dario R; Stork, Björn

    2011-07-01

    Unc-51-like kinase 1 (Ulk1) plays a central role in autophagy induction. It forms a stable complex with Atg13 and focal adhesion kinase (FAK) family interacting protein of 200 kDa (FIP 200). This complex is negatively regulated by the mammalian target of rapamycin complex 1 (mTORC1) in a nutrient-dependent way. AMP-activated protein kinase (AMPK), which is activated by LKB1/Strad/Mo25 upon high AMP levels, stimulates autophagy by inhibiting mTORC1. Recently, it has been described that AMPK and Ulk1 interact and that the latter is phosphorylated by AMPK. This phosphorylation leads to the direct activation of Ulk1 by AMPK bypassing mTOR-inhibition. Here we report that Ulk1/2 in turn phosphorylates all three subunits of AMPK and thereby negatively regulates its activity. Thus, we propose that Ulk1 is not only involved in the induction of autophagy, but also in terminating signaling events that trigger autophagy. In our model, phosphorylation of AMPK by Ulk1 represents a negative feedback circuit. PMID:21460634

  1. An insulin signaling feedback loop regulates pancreas progenitor cell differentiation during islet development and regeneration.

    PubMed

    Ye, Lihua; Robertson, Morgan A; Mastracci, Teresa L; Anderson, Ryan M

    2016-01-15

    As one of the key nutrient sensors, insulin signaling plays an important role in integrating environmental energy cues with organism growth. In adult organisms, relative insufficiency of insulin signaling induces compensatory expansion of insulin-secreting pancreatic beta (β) cells. However, little is known about how insulin signaling feedback might influence neogenesis of β cells during embryonic development. Using genetic approaches and a unique cell transplantation system in developing zebrafish, we have uncovered a novel role for insulin signaling in the negative regulation of pancreatic progenitor cell differentiation. Blocking insulin signaling in the pancreatic progenitors hastened the expression of the essential β cell genes insulin and pdx1, and promoted β cell fate at the expense of alpha cell fate. In addition, loss of insulin signaling promoted β cell regeneration and destabilization of alpha cell character. These data indicate that insulin signaling constitutes a tunable mechanism for β cell compensatory plasticity during early development. Moreover, using a novel blastomere-to-larva transplantation strategy, we found that loss of insulin signaling in endoderm-committed blastomeres drove their differentiation into β cells. Furthermore, the extent of this differentiation was dependent on the function of the β cell mass in the host. Altogether, our results indicate that modulation of insulin signaling will be crucial for the development of β cell restoration therapies for diabetics; further clarification of the mechanisms of insulin signaling in β cell progenitors will reveal therapeutic targets for both in vivo and in vitro β cell generation. PMID:26658317

  2. Phytochrome Signaling in Green Arabidopsis Seedlings: Impact Assessment of a Mutually Negative phyB–PIF Feedback Loop

    PubMed Central

    Leivar, Pablo; Monte, Elena; Cohn, Megan M.; Quail, Peter H.

    2012-01-01

    The reversibly red (R)/far-red (FR)-light-responsive phytochrome (phy) photosensory system initiates both the deetiolation process in dark-germinated seedlings upon first exposure to light, and the shade-avoidance process in fully deetiolated seedlings upon exposure to vegetational shade. The intracellular signaling pathway from the light-activated photoreceptor conformer (Pfr) to the transcriptional network that drives these responses involves direct, physical interaction of Pfr with a small subfamily of bHLH transcription factors, termed Phy-Interacting Factors (PIFs), which induces rapid PIF proteolytic degradation. In addition, there is evidence of further complexity in light-grown seedlings, whereby phyB–PIF interaction reciprocally induces phyB degradation, in a mutually-negative, feedback-loop configuration. Here, to assess the relative contributions of these antagonistic activities to the net phenotypic readout in light-grown seedlings, we have examined the magnitude of the light- and simulated-shade-induced responses of a pentuple phyBpif1pif3pif4pif5 (phyBpifq) mutant and various multiple pif-mutant combinations. The data (1) reaffirm that phyB is the predominant, if not exclusive, photoreceptor imposing the inhibition of hypocotyl elongation in deetiolating seedlings in response to prolonged continuous R irradiation and (2) show that the PIF quartet (PIF1, PIF3, PIF4, and PIF5) retain and exert a dual capacity to modulate hypocotyl elongation under these conditions, by concomitantly promoting cell elongation through intrinsic transcriptional-regulatory activity, and reducing phyB-inhibitory capacity through feedback-loop-induced phyB degradation. In shade-exposed seedlings, immunoblot analysis shows that the shade-imposed reduction in Pfr levels induces increases in the abundance of PIF3, and mutant analysis indicates that PIF3 acts, in conjunction with PIF4 and PIF5, to promote the known shade-induced acceleration of hypocotyl elongation. Conversely, although the quadruple pifq mutant displays clearly reduced hypocotyl elongation compared to wild-type in response to prolonged shade, immunoblot analysis detects no elevation in phyB levels in the mutant seedlings compared to the wild-type during the majority of the shade-induced growth period, and phyB levels are not robustly correlated with the growth phenotype across the pif-mutant combinations compared. These results suggest that PIF feedback modulation of phyB abundance does not play a dominant role in modulating the magnitude of the PIF-promoted, shade-responsive phenotype under these conditions. In seedlings grown under diurnal light–dark cycles, the data show that FR-pulse-induced removal of Pfr at the beginning of the dark period (End-of-Day-FR (EOD-FR) treatment) results in longer hypocotyls relative to no EOD-FR treatment and that this effect is attenuated in the pif-mutant combinations tested. This result similarly indicates that the PIF quartet members are capable of intrinsically promoting hypocotyl cell elongation in light-grown plants, independently of the effects of PIF feedback modulation of photoactivated-phyB abundance. PMID:22492120

  3. The calcium feedback loop and T cell activation: how cytoskeleton networks control intracellular calcium flux.

    PubMed

    Joseph, Noah; Reicher, Barak; Barda-Saad, Mira

    2014-02-01

    During T cell activation, the engagement of a T cell with an antigen-presenting cell (APC) results in rapid cytoskeletal rearrangements and a dramatic increase of intracellular calcium (Ca(2+)) concentration, downstream to T cell antigen receptor (TCR) ligation. These events facilitate the organization of an immunological synapse (IS), which supports the redistribution of receptors, signaling molecules and organelles towards the T cell-APC interface to induce downstream signaling events, ultimately supporting T cell effector functions. Thus, Ca(2+) signaling and cytoskeleton rearrangements are essential for T cell activation and T cell-dependent immune response. Rapid release of Ca(2+) from intracellular stores, e.g. the endoplasmic reticulum (ER), triggers the opening of Ca(2+) release-activated Ca(2+) (CRAC) channels, residing in the plasma membrane. These channels facilitate a sustained influx of extracellular Ca(2+) across the plasma membrane in a process termed store-operated Ca(2+) entry (SOCE). Because CRAC channels are themselves inhibited by Ca(2+) ions, additional factors are suggested to enable the sustained Ca(2+) influx required for T cell function. Among these factors, we focus here on the contribution of the actin and microtubule cytoskeleton. The TCR-mediated increase in intracellular Ca(2+) evokes a rapid cytoskeleton-dependent polarization, which involves actin cytoskeleton rearrangements and microtubule-organizing center (MTOC) reorientation. Here, we review the molecular mechanisms of Ca(2+) flux and cytoskeletal rearrangements, and further describe the way by which the cytoskeletal networks feedback to Ca(2+) signaling by controlling the spatial and temporal distribution of Ca(2+) sources and sinks, modulating TCR-dependent Ca(2+) signals, which are required for an appropriate T cell response. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé. PMID:23860253

  4. UBTD1 induces cellular senescence through an UBTD1-Mdm2/p53 positive feedback loop.

    PubMed

    Zhang, Xiao-Wei; Wang, Xiao-Feng; Ni, Su-Jie; Qin, Wei; Zhao, Li-Qin; Hua, Rui-Xi; Lu, You-Wei; Li, Jin; Dimri, Goberdhan P; Guo, Wei-Jian

    2015-03-01

    The tumour suppressor p53 plays an important role in tumourigenesis. Besides inducing apoptosis, it regulates cellular senescence, which constitutes an important barrier to tumourigenesis. The mechanism of regulation of cellular senescence by p53 and its downstream pathway are poorly understood. Here, we report that the ubiquitin domain-containing 1 (UBTD1) gene, a new downstream target of p53, induces cellular senescence and acts as a novel tumour suppressor by a mechanism that depends on p53. Expression of UBTD1 increased upon cellular senescence induced by serial passageing of cultures, as well as by exposure to DNA-damageing drugs that induce premature senescence. Over-expression of UBTD1 induces senescence in human fibroblasts and cancer cells and attenuation of the transformed phenotype in cancer cells. UBTD1 is down-regulated in gastric and colorectal cancer tissues, and its lower expression correlates with a more aggressive phenotype and worse prognosis. Multivariate analysis revealed that UBTD1 expression was an independent prognostic factor for gastric cancer patients. Furthermore, UBTD1 increased the stability of p53 protein, by promoting the degradation of Mdm2 protein. Importantly, UBTD1 and p53 function mutually depend on each other in regulating cellular senescence and proliferation. Thus, our data suggest that, upon DNA damage, p53 induction by UBTD1 creates a positive feedback mechanism to further increase p53 expression. Our results establish UBTD1 as a regulator of cellular senescence that mediates p53 function, and provide insights into the mechanism of Mdm2 inhibition that impacts p53 dynamics during cellular senescence and tumourigenesis. PMID:25382750

  5. Progress toward controlling in vivo fibrillating sheep atria using a nonlinear-dynamics-based closed-loop feedback method

    NASA Astrophysics Data System (ADS)

    Gauthier, Daniel J.; Hall, G. Martin; Oliver, Robert A.; Dixon-Tulloch, Ellen G.; Wolf, Patrick D.; Bahar, Sonya

    2002-09-01

    We describe preliminary experiments on controlling in vivo atrial fibrillation using a closed-loop feedback protocol that measures the dynamics of the right atrium at a single spatial location and applies control perturbations at a single spatial location. This study allows investigation of control of cardiac dynamics in a preparation that is physiologically close to an in vivo human heart. The spatial-temporal response of the fibrillating sheep atrium is measured using a multi-channel electronic recording system to assess the control effectiveness. In an attempt to suppress fibrillation, we implement a scheme that paces occasionally the cardiac muscle with small shocks. When successful, the inter-activation time interval is the same and electrical stimuli are only applied when the controller senses that the dynamics are beginning to depart from the desired periodic rhythm. The shock timing is adjusted in real time using a control algorithm that attempts to synchronize the most recently measured inter-activation interval with the previous interval by inducing an activation at a time projected by the algorithm. The scheme is "single-sided" in that it can only shorten the inter-activation time but not lengthen it. Using probability distributions of the inter-activation time intervals, we find that the feedback protocol is not effective in regularizing the dynamics. One possible reason for the less-than-successful results is that the controller often attempts to stimulate the tissue while it is still in the refractory state and hence it does not induce an activation.

  6. Early development of the thalamic inhibitory feedback loop in the primary somatosensory system of the newborn mice.

    PubMed

    Evrard, Alexis; Ropert, Nicole

    2009-08-01

    Spontaneous neuronal activity plays an important role during the final development of the brain circuits and the formation of the primary sensory maps. In young rats, spindle bursts have been recorded in the primary somatosensory cortex. They are correlated with spontaneous muscle twitches and occur before active whisking. They bear similarities with the spindles recorded in adult brain that occur during early stages of sleep and rely on a thalamic feedback loop between the glutamatergic nucleus ventroposterior medialis (nVPM) and the GABAergic nucleus reticularis thalami (nRT). However, whether a functional nVPM-nRT loop exists in newborn rodents is unknown. We studied the reciprocal synaptic connections between nVPM and nRT in thalamic acute slices from mice from birth [postnatal day 0 (P0)] until P9. We first demonstrated that nVPM-to-nRT EPSCs could be distinguished from corticothalamic EPSCs by their inhibition by 5-HT attributable to the transient expression of functional presynaptic serotonin 1B receptors. The nVPM-to-nRT EPSCs and nRT-to-nVPM IPSCs were both detected the first day after birth; their amplitude near 2 nS was relatively stable until P5. At P6-P7, there was a rapid and simultaneous increase of both nVPM-to-nRT EPSCs and nRT-to-nVPM IPSCs that reached 8 and 9 nS, respectively. Our results show that the thalamic synapses implicated in spindle activity are functional shortly after birth, suggesting that they could already generate spindles during the first postnatal week. Our results also suggest an inhibitory action of 5-HT on the spindle bursts of the newborn mice. PMID:19657043

  7. A calcium-redox feedback loop controls human monocyte immune responses: The role of ORAI Ca2+ channels.

    PubMed

    Saul, Stephanie; Gibhardt, Christine S; Schmidt, Barbara; Lis, Annette; Pasieka, Bastian; Conrad, David; Jung, Philipp; Gaupp, Rosmarie; Wonnenberg, Bodo; Diler, Ebru; Stanisz, Hedwig; Vogt, Thomas; Schwarz, Eva C; Bischoff, Markus; Herrmann, Mathias; Tschernig, Thomas; Kappl, Reinhard; Rieger, Heiko; Niemeyer, Barbara A; Bogeski, Ivan

    2016-01-01

    In phagocytes, pathogen recognition is followed by Ca(2+) mobilization and NADPH oxidase 2 (NOX2)-mediated "oxidative burst," which involves the rapid production of large amounts of reactive oxygen species (ROS). We showed that ORAI Ca(2+) channels control store-operated Ca(2+) entry, ROS production, and bacterial killing in primary human monocytes. ROS inactivate ORAI channels that lack an ORAI3 subunit. Staphylococcal infection of mice reduced the expression of the gene encoding the redox-sensitive Orai1 and increased the expression of the gene encoding the redox-insensitive Orai3 in the lungs or in bronchoalveolar lavages. A similar switch from ORAI1 to ORAI3 occurred in primary human monocytes exposed to bacterial peptides in culture. These alterations in ORAI1 and ORAI3 abundance shifted the channel assembly toward a more redox-insensitive configuration. Accordingly, silencing ORAI3 increased the redox sensitivity of the channel and enhanced oxidation-induced inhibition of NOX2. We generated a mathematical model that predicted additional features of the Ca(2+)-redox interplay. Our results identified the ORAI-NOX2 feedback loop as a determinant of monocyte immune responses. PMID:26956485

  8. The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells

    PubMed Central

    Gao, Yuan; Wu, Fuju; Zhou, Jichun; Yan, Lei; Jurczak, Michael J.; Lee, Hui-Young; Yang, Lihua; Mueller, Martin; Zhou, Xiao-Bo; Dandolo, Luisa; Szendroedi, Julia; Roden, Michael; Flannery, Clare; Taylor, Hugh; Carmichael, Gordon G.; Shulman, Gerald I.; Huang, Yingqun

    2014-01-01

    The H19 lncRNA has been implicated in development and growth control and is associated with human genetic disorders and cancer. Acting as a molecular sponge, H19 inhibits microRNA (miRNA) let-7. Here we report that H19 is significantly decreased in muscle of human subjects with type-2 diabetes and insulin resistant rodents. This decrease leads to increased bioavailability of let-7, causing diminished expression of let-7 targets, which is recapitulated in vitro where H19 depletion results in impaired insulin signaling and decreased glucose uptake. Furthermore, acute hyperinsulinemia downregulates H19, a phenomenon that occurs through PI3K/AKT-dependent phosphorylation of the miRNA processing factor KSRP, which promotes biogenesis of let-7 and its mediated H19 destabilization. Our results reveal a previously undescribed double-negative feedback loop between sponge lncRNA and target miRNA that contributes to glucose regulation in muscle cells. PMID:25399420

  9. Broadband and wide-range feedback tuning scheme for phase-locked loop stabilization of tunable optoelectronic oscillators.

    PubMed

    Xu, Xingyuan; Dai, Jian; Dai, Yitang; Yin, Feifei; Zhou, Yue; Li, Jianqiang; Yin, Jie; Wang, Qunyang; Xu, Kun

    2015-12-15

    In this Letter, we propose and experimentally demonstrate a novel broadband and wide-range feedback tuning scheme for phase-locked loop (PLL) stabilization of tunable optoelectronic oscillators (OEO). The proposed scheme was realized in a simple and feasible way based on a dual-parallel Mach-Zehnder modulator (DPMZM) and optical bandpass filter (OBPF). The wide RF phase-shift range and broadband performance of the proposed scheme were demonstrated theoretically and experimentally, which ensured OEO's wide operating temperature range and tunability in PLL stabilization. As a result, PLL stabilization for OEO was achieved at different oscillating frequencies and the long-term stability was greatly improved without any thermal control. The measured overlapping Allan deviation of PLL-locked OEO reached lower than 10-10 after 1000-s averaging time, which was four orders of magnitude better than the free-running OEO. The phase noise performance was also improved at low-offset frequencies and remained the same at high-offset frequencies. PMID:26670530

  10. A Regulatory Feedback Loop between RpoS and SpoT Supports the Survival of Legionella pneumophila in Water

    PubMed Central

    Trigui, Hana; Dudyk, Paulina; Oh, Jinrok; Hong, Jong-In

    2014-01-01

    Legionella pneumophila is a waterborne pathogen, and survival in the aquatic environment is central to its transmission to humans. Therefore, identifying genes required for its survival in water could help prevent Legionnaires' disease outbreaks. In the present study, we investigate the role of the sigma factor RpoS in promoting survival in water, where L. pneumophila experiences severe nutrient deprivation. The rpoS mutant showed a strong survival defect compared to the wild-type strain in defined water medium. The transcriptome of the rpoS mutant during exposure to water revealed that RpoS represses genes associated with replication, translation, and transcription, suggesting that the mutant fails to shut down major metabolic programs. In addition, the rpoS mutant is transcriptionally more active than the wild-type strain after water exposure. This could be explained by a misregulation of the stringent response in the rpoS mutant. Indeed, the rpoS mutant shows an increased expression of spoT and a corresponding decrease in the level of (p)ppGpp, which is due to the presence of a negative feedback loop between RpoS and SpoT. Therefore, the lack of RpoS causes an aberrant regulation of the stringent response, which prevents the induction of a successful response to starvation. PMID:25416763

  11. Epigenetic inactivation of the CpG demethylase TET1 as a DNA methylation feedback loop in human cancers.

    PubMed

    Li, Lili; Li, Chen; Mao, Haitao; Du, Zhenfang; Chan, Wai Yee; Murray, Paul; Luo, Bing; Chan, Anthony Tc; Mok, Tony Sk; Chan, Francis Kl; Ambinder, Richard F; Tao, Qian

    2016-01-01

    Promoter CpG methylation is a fundamental regulatory process of gene expression. TET proteins are active CpG demethylases converting 5-methylcytosine to 5-hydroxymethylcytosine, with loss of 5 hmC as an epigenetic hallmark of cancers, indicating critical roles of TET proteins in epigenetic tumorigenesis. Through analysis of tumor methylomes, we discovered TET1 as a methylated target, and further confirmed its frequent downregulation/methylation in cell lines and primary tumors of multiple carcinomas and lymphomas, including nasopharyngeal, esophageal, gastric, colorectal, renal, breast and cervical carcinomas, as well as non-Hodgkin, Hodgkin and nasal natural killer/T-cell lymphomas, although all three TET family genes are ubiquitously expressed in normal tissues. Ectopic expression of TET1 catalytic domain suppressed colony formation and induced apoptosis of tumor cells of multiple tissue types, supporting its role as a broad bona fide tumor suppressor. Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9. As only infrequent mutations of TET1 have been reported, compared to TET2, epigenetic silencing therefore appears to be the dominant mechanism for TET1 inactivation in cancers, which also forms a feedback loop of CpG methylation during tumorigenesis. PMID:27225590

  12. Positive feedback loop between introductions of non-native marine species and cultivation of oysters in Europe.

    PubMed

    Mineur, Frederic; Le Roux, Auguste; Maggs, Christine A; Verlaque, Marc

    2014-12-01

    With globalization, agriculture and aquaculture activities are increasingly affected by diseases that are spread through movement of crops and stock. Such movements are also associated with the introduction of non-native species via hitchhiking individual organisms. The oyster industry, one of the most important forms of marine aquaculture, embodies these issues. In Europe disease outbreaks affecting cultivated populations of the naturalized oyster Crassostrea gigas caused a major disruption of production in the late 1960s and early 1970s. Mitigation procedures involved massive imports of stock from the species' native range in the northwestern Pacific from 1971 to 1977. We assessed the role stock imports played in the introduction of non-native marine species (including pathogens) from the northwestern Pacific to Europe through a methodological and critical appraisal of record data. The discovery rate of non-native species (a proxy for the introduction rate) from 1966 to 2012 suggests a continuous vector activity over the entire period. Disease outbreaks that have been affecting oyster production since 2008 may be a result of imports from the northwestern Pacific, and such imports are again being considered as an answer to the crisis. Although successful as a remedy in the short and medium terms, such translocations may bring new diseases that may trigger yet more imports (self-reinforcing or positive feedback loop) and lead to the introduction of more hitchhikers. Although there is a legal framework to prevent or reduce these introductions, existing procedures should be improved. PMID:25047099

  13. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation.

    PubMed

    Rishi, Loveena; Hannon, Maura; Salomè, Mara; Hasemann, Marie; Frank, Anne-Katrine; Campos, Joana; Timoney, Jennifer; O'Connor, Caitriona; Cahill, Mary R; Porse, Bo; Keeshan, Karen

    2014-04-10

    The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein α (C/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C/EBPα-p42, and in normal granulocyte/macrophage progenitor cells, we detect C/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C/EBPα and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant hematopoiesis. PMID:24516045

  14. INSM1 increases N-myc stability and oncogenesis via a positive-feedback loop in neuroblastoma

    PubMed Central

    Chen, Chiachen; Breslin, Mary B.; Lan, Michael S.

    2015-01-01

    Insulinoma associated-1 (IA-1/INSM1) gene is exclusively expressed during early embryonic development, but has been found to be re-expressed at high levels in neuroendocrine tumors including neuroblastoma. Using over-expression and knockdown experiments in neuroblastoma cells, we showed that INSM1 is critical for cell proliferation, BME-coated invasion, and soft agar colony formation. Here, we identified INSM1 as a novel target gene activated by N-myc in N-myc amplified neuroblastoma cells. The Sonic hedgehog signaling pathway induced INSM1 by increasing N-myc expression. INSM1 activated PI3K/AKT/GSK3β pathways to suppress N-myc phosphorylation (Thr-58) and inhibited degradation of N-myc. Inversely, N-myc protein bound to the E2-box region of the INSM1 promoter and activated INSM1 expression. The invasion assay and the xenograft nude mouse tumor model revealed that the INSM1 factor facilitated growth and oncogenesis of neuroblastoma. The current data supports our hypothesis that a positive-feedback loop of sonic hedgehog signaling induced INSM1 through N-myc and INSM1 enhanced N-myc stability contributing to the transformation of human neuroblastoma. PMID:26456864

  15. DLK1 Regulates Whole-Body Glucose Metabolism: A Negative Feedback Regulation of the Osteocalcin-Insulin Loop.

    PubMed

    Abdallah, Basem M; Ditzel, Nicholas; Laborda, Jorge; Karsenty, Gerard; Kassem, Moustapha

    2015-09-01

    The endocrine role of the skeleton in regulating energy metabolism is supported by a feed-forward loop between circulating osteoblast (OB)-derived undercarboxylated osteocalcin (Glu-OCN) and pancreatic ?-cell insulin; in turn, insulin favors osteocalcin (OCN) bioactivity. These data suggest the existence of a negative regulation of this cross talk between OCN and insulin. Recently, we identified delta like-1 (DLK1) as an endocrine regulator of bone turnover. Because DLK1 is colocalized with insulin in pancreatic ?-cells, we examined the role of DLK1 in insulin signaling in OBs and energy metabolism. We show that Glu-OCN specifically stimulates Dlk1 expression by the pancreas. Conversely, Dlk1-deficient (Dlk1(-/-) ) mice exhibited increased circulating Glu-OCN levels and increased insulin sensitivity, whereas mice overexpressing Dlk1 in OB displayed reduced insulin secretion and sensitivity due to impaired insulin signaling in OB and lowered Glu-OCN serum levels. Furthermore, Dlk1(-/-) mice treated with Glu-OC experienced significantly lower blood glucose levels than Glu-OCN-treated wild-type mice. The data suggest that Glu-OCN-controlled production of DLK1 by pancreatic ?-cells acts as a negative feedback mechanism to counteract the stimulatory effects of insulin on OB production of Glu-OCN, a potential mechanism preventing OCN-induced hypoglycemia. PMID:25918236

  16. Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop

    SciTech Connect

    Lai, Serene R.; Cunningham, Amanda P.; Huynh, Vu Q.; Andrews, Lucy G.; Tollefsbol, Trygve O. . E-mail: trygve@uab.edu

    2007-01-15

    The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the enzyme telomerase which is responsible for telomeric maintenance and extension. Using RNA interference to knock down hTERT mRNA expression, we provide evidence that hTERT exerts extra-telomeric effects on the cell cycle and on its own regulatory proteins, specifically: p53 and p21. We tested our hypothesis that hTERT regulates its own expression through effects on upstream regulatory genes using transformed human embryonic kidney (HEK 293) cells, p53 and p16 {sup INK4a} null human ovarian cancer SKOV-3 cells, and p53-null MDA-MB-157 human mammary cancer cells. In HEK 293 cells, hTERT knockdown resulted in elevated p53 and p21 transcription and a decrease in cellular proliferation. Similar results were observed in the MDA-MB-157 cell line where p21 was upregulated, correlating with cell growth inhibition. In contrast, we observed a decrease in expression of p21 in SKOV-3 cells with hTERT knockdown and cell growth appeared to be unaffected. These findings suggest that hTERT may be involved in a feedback loop system, thereby playing a role in its own regulation.

  17. Runx2/miR-3960/miR-2861 Positive Feedback Loop Is Responsible for Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells

    PubMed Central

    Xia, Zhu-Ying; Hu, Yin; Xie, Ping-Li; Tang, Si-Yuan; Luo, Xiang-Hang; Liao, Er-Yuan; Chen, Fei; Xie, Hui

    2015-01-01

    We previously reported that Runx2/miR-3960/miR-2861 regulatory feedback loop stimulates osteoblast differentiation. However, the effect of this feedback loop on the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) remains unclear. Our recent study showed that miR-2861 and miR-3960 expression increases significantly during β-glycerophosphate-induced osteogenic transdifferentiation of VSMCs. Overexpression of miR-2861 or miR-3960 in VSMCs enhances β-glycerophosphate-induced osteoblastogenesis, whereas inhibition of miR-2861 or miR-3960 expression attenuates it. MiR-2861 or miR-3960 promotes osteogenic transdifferentiation of VSMCs by targeting histone deacetylase 5 or Homeobox A2, respectively, resulting in increased runt-related transcription factor 2 (Runx2) protein production. Furthermore, overexpression of Runx2 induces miR-2861 and miR-3960 transcription, and knockdown of Runx2 attenuates β-glycerophosphate-induced miR-2861 and miR-3960 transcription in VSMCs. Thus, our data show that Runx2/miR-3960/miR-2861 positive feedback loop plays an important role in osteogenic transdifferentiation of VSMCs and contributes to vascular calcification. PMID:26221600

  18. Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats.

    PubMed

    Cui, Zhuang; Xu, Changpeng; Li, Xue; Song, Jinqi; Yu, Bin

    2015-05-01

    Osteoarthritis (OA) is a most commonly multifactorial degenerative joint disease along with the aging population, particularly in postmenopausal women. During the onset of OA, articular cartilage and subchondral bone act in concert as a functional unit. This present study is to investigate the effects of early or late treatment with recombinant lubricin on the onset of osteoarthritis (OA) in ovariectomized (OVX) rats. We found that both early and late recombinant lubricin treatments attenuated the onset of OA by positive feedback loop between articular cartilage and subchondral bone, although late treatment contributed to a lesser effect compared with early treatment. Specifically, treatment with recombinant lubricin protected articular cartilage from degeneration, demonstrated by lower proteoglycan loss, lower OARSI scores, less calcification cartilage zone and reduced immunostaining for collagen X (Col X) and matrix metalloproteinase (MMP-13) but increased the expression of lubricin, in comparison with vehicle-treated OVX rat group. Further, chondroprotective effects of lubricin normalized bone remodeling in subchondral bone underneath. It's suggested that treatment with recombinant lubricin inhibited the elevation of TRAP and Osterix positive cells in OVX rats and led to the normalization of subchondral bone microarchitectures with the suppression of subsidence of bone volume ratio (BV/TV) and trabecular thickness (Tb.Th) and the increase of trabecular separation (Tb.Sp) in vehicle-treated OVX rats. What's more, the normalization of subchondral bone in turn attenuated the articular cartilage erosion by inhibiting vascular invasion from subchondral bone to calcified cartilage zone, exemplified by inhibiting the elevation of CD31 positive cells in calcified cartilage and angiography in subchondral bone. Together, these results shed light that both early and late recombinant lubricin treatments attenuate the onset of OA by balancing the interplay between articular cartilage and subchondral bone in OVX rats, while also providing a further rationale for its therapeutic targeting to postmenopausal OA and suggesting that treatment timing is a pivotal factor for better effect acquisition. PMID:25576671

  19. A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion.

    PubMed

    Hetmanski, Joseph H R; Zindy, Egor; Schwartz, Jean-Marc; Caswell, Patrick T

    2016-05-01

    Cell migration in 3D microenvironments is fundamental to development, homeostasis and the pathobiology of diseases such as cancer. Rab-coupling protein (RCP) dependent co-trafficking of α5β1 and EGFR1 promotes cancer cell invasion into fibronectin (FN) containing extracellular matrix (ECM), by potentiating EGFR1 signalling at the front of invasive cells. This promotes a switch in RhoGTPase signalling to inhibit Rac1 and activate a RhoA-ROCK-Formin homology domain-containing 3 (FHOD3) pathway and generate filopodial actin-spike protrusions which drive invasion. To further understand the signalling network that drives RCP-driven invasive migration, we generated a Boolean logical model based on existing network pathways/models, where each node can be interrogated by computational simulation. The model predicted an unanticipated feedback loop, whereby Raf/MEK/ERK signalling maintains suppression of Rac1 by inhibiting the Rac-activating Sos1-Eps8-Abi1 complex, allowing RhoA activity to predominate in invasive protrusions. MEK inhibition was sufficient to promote lamellipodia formation and oppose filopodial actin-spike formation, and led to activation of Rac and inactivation of RhoA at the leading edge of cells moving in 3D matrix. Furthermore, MEK inhibition abrogated RCP/α5β1/EGFR1-driven invasive migration. However, upon knockdown of Eps8 (to suppress the Sos1-Abi1-Eps8 complex), MEK inhibition had no effect on RhoGTPase activity and did not oppose invasive migration, suggesting that MEK-ERK signalling suppresses the Rac-activating Sos1-Abi1-Eps8 complex to maintain RhoA activity and promote filopodial actin-spike formation and invasive migration. Our study highlights the predictive potential of mathematical modelling approaches, and demonstrates that a simple intervention (MEK-inhibition) could be of therapeutic benefit in preventing invasive migration and metastasis. PMID:27138333

  20. MicroRNA-19a and CD22 Comprise a Feedback Loop for B Cell Response in Sepsis

    PubMed Central

    Jiang, Yinan; Zhou, Hongmin; Ma, Dandan; Chen, Zhonghua Klaus; Cai, Xun

    2015-01-01

    Background MicroRNA-19a (miR-19a), an oncogenic microRNA, has been recently reported to target CD22 in B cell lymphoma cell lines, but its role in inflammatory response is unclear. CD22 is a negative regulator for BCR signaling, and we hypothesize that miR-19a regulates B cell response by targeting CD22 in sepsis. Material/Methods In order to determine whether miR-19a-CD22 pathway was involved in sepsis, and what role it played in the regulatory mechanisms, we detected the levels of miR-19a in B cells obtained from patients with sepsis, and measured the levels of miR-19a and CD22 expression in B cells activated by LPS in vitro. Additionally, we investigated the correlation between miR-19a and CD22, as well as the influence of this pathway on BCR signaling, in transfected B cells. Results We found that septic patients displayed up-regulated miR-19a in B cells. In vitro, miR-19a was increased in activated B cells, with CD22 expression initially enhanced but subsequently decreased. Moreover, overexpression of miR-19a resulted in an amplified BCR signaling, while overexpression of CD22 attenuated the effect of miR-19a and increased its expression. Conclusions Our study demonstrated that miR-19a and CD22 comprised a feedback loop for B cell response in sepsis, providing a potential therapeutic target to recover the immune homeostasis. PMID:26017478

  1. An epigenetic auto-feedback loop regulates TGF-β type II receptor expression and function in NSCLC.

    PubMed

    Yang, Shanzhong; Cho, Yong-Jig; Jin, Lin; Yuan, Guandou; Datta, Arunima; Buckhaults, Phillip; Datta, Pran K

    2015-10-20

    The downregulation of transforming growth factor-β (TGF-β) type II receptor (TβRII) expression and function plays a pivotal role in the loss of the TGF-β-induced tumor suppressor function that contributes to lung cancer progression. The aberrant expression of miRNAs has been shown to be involved in the regulation of oncogenes and tumor suppressor genes. Our current study involving miRNA microarray, northern blot and QRT-PCR analysis shows an inverse correlation between miR-20a and TβRII expression in non-small cell lung cancer (NSCLC) tissues and cell lines. Stable expression of miR-20a downregulates TβRII in lung epithelial cells which results in an inhibition of TGF-β signaling and attenuation of TGF-β-induced cell growth suppression and apoptosis. Stable knock down of miR-20a increases TβRII expression and inhibits tumorigenicity of lung cancer cells in vivo. Oncogene c-Myc promotes miR-20a expression by activating its promoter leading to downregulation of TβRII expression and TGF-ß signaling. MiR-145, which is upregulated by TGF-β, inhibits miR-20a expression by targeting c-Myc and upregulates TβRII expression. These correlations among miRNAs and cellular proteins are supported by TCGA public database using NSCLC specimens. These results suggest a novel mechanism for the loss of TβRII expression and TGF-β-induced tumor suppressor functions in lung cancer through a complex auto-feedback loop TGF-β/miR-145/c-Myc/miR-20a/TβRII. PMID:26356817

  2. An epigenetic auto-feedback loop regulates TGF-β type II receptor expression and function in NSCLC

    PubMed Central

    Jin, Lin; Yuan, Guandou; Datta, Arunima; Buckhaults, Phillip; Datta, Pran K.

    2015-01-01

    The downregulation of transforming growth factor-β (TGF-β) type II receptor (TβRII) expression and function plays a pivotal role in the loss of the TGF-β-induced tumor suppressor function that contributes to lung cancer progression. The aberrant expression of miRNAs has been shown to be involved in the regulation of oncogenes and tumor suppressor genes. Our current study involving miRNA microarray, northern blot and QRT-PCR analysis shows an inverse correlation between miR-20a and TβRII expression in non-small cell lung cancer (NSCLC) tissues and cell lines. Stable expression of miR-20a downregulates TβRII in lung epithelial cells which results in an inhibition of TGF-β signaling and attenuation of TGF-β-induced cell growth suppression and apoptosis. Stable knock down of miR-20a increases TβRII expression and inhibits tumorigenicity of lung cancer cells in vivo. Oncogene c-Myc promotes miR-20a expression by activating its promoter leading to downregulation of TβRII expression and TGF-Δ signaling. MiR-145, which is upregulated by TGF-β, inhibits miR-20a expression by targeting c-Myc and upregulates TβRII expression. These correlations among miRNAs and cellular proteins are supported by TCGA public database using NSCLC specimens. These results suggest a novel mechanism for the loss of TβRII expression and TGF-β-induced tumor suppressor functions in lung cancer through a complex auto-feedback loop TGF-β/miR-145/c-Myc/miR-20a/TβRII. PMID:26356817

  3. Cushing Syndrome Due to ACTH-Secreting Pheochromocytoma, Aggravated by Glucocorticoid-Driven Positive-Feedback Loop

    PubMed Central

    Sakuma, Ikki; Higuchi, Seiichiro; Fujimoto, Masanori; Takiguchi, Tomoko; Nakayama, Akitoshi; Tamura, Ai; Kohno, Takashi; Komai, Eri; Shiga, Akina; Nagano, Hidekazu; Hashimoto, Naoko; Suzuki, Sawako; Mayama, Takafumi; Koide, Hisashi; Ono, Katsuhiko; Sasano, Hironobu; Tatsuno, Ichiro; Yokote, Koutaro

    2016-01-01

    Context: Pheochromocytoma is a catecholamine-producing tumor that originates from adrenal chromaffin cells and is capable of secreting various hormones, including ACTH. Case Description: A 56-year-old female presented with Cushingoid appearance and diabetic ketoacidosis. Endocrinological examinations demonstrated ectopic ACTH production with hypercortisolemia and excess urinary cortisol accompanied by elevated plasma and urine catecholamines. Computed tomography revealed a large left adrenal tumor with bilateral adrenal enlargement. Metaiodobenzylguanidine scintigraphy revealed abnormal accumulation in the tumor, which was eventually diagnosed as pheochromocytoma with ectopic ACTH secretion with subsequent manifestation of Cushing's syndrome. Ectopic ACTH secretion and catecholamine production were blocked by metyrapone treatment, whereas dexamethasone paradoxically increased ACTH secretion. Left adrenalectomy resulted in complete remission of Cushing's syndrome and pheochromocytoma. In Vitro Studies: Immunohistological analysis revealed that the tumor contained two functionally distinct chromaffin-like cell types. The majority of tumor cells stained positive for tyrosine hydroxylase (TH), whereas a minor population of ACTH-positive tumor cells was negative for TH. Furthermore, gene expression and in vitro functional analyses using primary tumor tissue cultures demonstrated that dexamethasone facilitated ACTH as well as catecholamine secretion with parallel induction of proopiomelanocortin (POMC), TH, and phenylethanolamine N-methyltransferase mRNA, supporting a glucocorticoid-dependent positive-feedback loop of ACTH secretion in vivo. DNA methylation analysis revealed that the POMC promoter of this tumor, particularly the E2F binding site, was hypomethylated. Conclusion: We present a case of ectopic ACTH syndrome associated with pheochromocytoma. ACTH up-regulation with paradoxical response to glucocorticoid, possibly through the hypomethylation of the POMC promoter, exacerbated the patient's condition. PMID:26700559

  4. A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion

    PubMed Central

    Hetmanski, Joseph H. R.; Zindy, Egor; Schwartz, Jean-Marc; Caswell, Patrick T.

    2016-01-01

    Cell migration in 3D microenvironments is fundamental to development, homeostasis and the pathobiology of diseases such as cancer. Rab-coupling protein (RCP) dependent co-trafficking of α5β1 and EGFR1 promotes cancer cell invasion into fibronectin (FN) containing extracellular matrix (ECM), by potentiating EGFR1 signalling at the front of invasive cells. This promotes a switch in RhoGTPase signalling to inhibit Rac1 and activate a RhoA-ROCK-Formin homology domain-containing 3 (FHOD3) pathway and generate filopodial actin-spike protrusions which drive invasion. To further understand the signalling network that drives RCP-driven invasive migration, we generated a Boolean logical model based on existing network pathways/models, where each node can be interrogated by computational simulation. The model predicted an unanticipated feedback loop, whereby Raf/MEK/ERK signalling maintains suppression of Rac1 by inhibiting the Rac-activating Sos1-Eps8-Abi1 complex, allowing RhoA activity to predominate in invasive protrusions. MEK inhibition was sufficient to promote lamellipodia formation and oppose filopodial actin-spike formation, and led to activation of Rac and inactivation of RhoA at the leading edge of cells moving in 3D matrix. Furthermore, MEK inhibition abrogated RCP/α5β1/EGFR1-driven invasive migration. However, upon knockdown of Eps8 (to suppress the Sos1-Abi1-Eps8 complex), MEK inhibition had no effect on RhoGTPase activity and did not oppose invasive migration, suggesting that MEK-ERK signalling suppresses the Rac-activating Sos1-Abi1-Eps8 complex to maintain RhoA activity and promote filopodial actin-spike formation and invasive migration. Our study highlights the predictive potential of mathematical modelling approaches, and demonstrates that a simple intervention (MEK-inhibition) could be of therapeutic benefit in preventing invasive migration and metastasis. PMID:27138333

  5. MicroRNA-155-IFN-γ Feedback Loop in CD4+T Cells of Erosive type Oral Lichen Planus

    PubMed Central

    Hu, Jing-Yu; Zhang, Jing; Ma, Jing-Zhi; Liang, Xue-Yi; Chen, Guan-Ying; Lu, Rui; Du, Ge-Fei; Zhou, Gang

    2015-01-01

    Oral lichen planus (OLP) is a T cell-mediated immune disorder, and we have indicated a Th1-dominated immune response in OLP. MicroRNA-155 (miR-155) could promote Th1 cells polarization. The present study aims to determine the role of miR-155 in immune response of OLP. The expression of miR-155 and the target mRNA was tested by Real-Time PCR. The serum levels of IL-2, 4, 10 and IFN-γ were examined with ELISA. Furthermore, in vitro study was built to observe the function of miR-155 in erosive-type OLP (EOLP). Finally, we determined the expression and correlation of miR-155 and SOCS1 in EOLP CD4+ T cells. The results showed miR-155 was high related with the disease severities. Besides, serum IFN-γ was specifically increased in EOLP group, while IL-4 was decreased. In vitro studies showed miR-155 could reinforce IFN-γ signal transducer, and the induction of IFN-γ could also promote miR-155 expression in EOLP CD4+ T cells. In addition, miR-155 levels were negatively related with SOCS1 mRNA expression in EOLP CD4+ T cells. Our study revealed a positive miR-155- IFN-γ feedback loop in EOLP CD4+ T cell, which might contribute to the Th1-dominated immune response. Furthermore, miR-155 could be used for the evaluation and treatment of OLP. PMID:26594049

  6. Combined prokaryotic-eukaryotic delivery and expression of therapeutic factors through a primed autocatalytic positive-feedback loop.

    PubMed

    Shi, Lei; Yu, Bin; Cai, Chun-Hui; Huang, Wei; Zheng, Bo-Jian; Smith, David Keith; Huang, Jian-Dong

    2016-01-28

    Progress in bacterial therapy for cancer and infectious diseases is hampered by the absence of safe and efficient vectors. Sustained delivery and high gene expression levels are critical for the therapeutic efficacy. Here we developed a Salmonella typhimrium strain to maintain and safely deliver a plasmid vector to target tissues. This vector is designed to allow dual transcription of therapeutic factors, such as cytotoxic proteins, short hairpin RNAs or combinations, in the nucleus or cytoplasm of eukaryotic cells, with this expression sustained by an autocatalytic positive-feedback loop. Mechanisms to prime the system and maintain the plasmid in the bacterium are also provided. Synergistic effects of attenuated Salmonella and our inter-kingdom system allow the precise expression of Diphtheria toxin A chain (DTA) gene in tumor microenvironment and eradicate large established tumors in immunocompetent animals. In the experiments reported here, 26% of mice (n=5/19) with aggressive tumors were cured and the others all survived until the end of the experiment. We also demonstrated that ST4 packaged with shRNA-encoding plasmids has sustained knockdown effects in nude mice bearing human MDA-MB-231 xenografts. Three weeks after injection of 5×10(6) ST4/pIKT-shPlk, PLK1 transcript levels in tumors were 62.5±18.6% lower than the vector control group (P=0.015). The presence of PLK1 5' RACE-PCR cleavage products confirmed a sustained RNAi-mediated mechanism of action. This innovative technology provides an effective and versatile vehicle for efficient inter-kingdom gene delivery that can be applied to cancer therapy and other purposes. PMID:26682504

  7. Exocytosis of serotonin from the neuronal soma is sustained by a serotonin and calcium-dependent feedback loop

    PubMed Central

    Leon-Pinzon, Carolina; Cercós, Montserrat G.; Noguez, Paula; Trueta, Citlali; De-Miguel, Francisco F.

    2014-01-01

    The soma of many neurons releases large amounts of transmitter molecules through an exocytosis process that continues for hundreds of seconds after the end of the triggering stimulus. Transmitters released in this way modulate the activity of neurons, glia and blood vessels over vast volumes of the nervous system. Here we studied how somatic exocytosis is maintained for such long periods in the absence of electrical stimulation and transmembrane Ca2+ entry. Somatic exocytosis of serotonin from dense core vesicles could be triggered by a train of 10 action potentials at 20 Hz in Retzius neurons of the leech. However, the same number of action potentials produced at 1 Hz failed to evoke any exocytosis. The 20-Hz train evoked exocytosis through a sequence of intracellular Ca2+ transients, with each transient having a different origin, timing and intracellular distribution. Upon electrical stimulation, transmembrane Ca2+ entry through L-type channels activated Ca2+-induced Ca2+ release. A resulting fast Ca2+ transient evoked an early exocytosis of serotonin from sparse vesicles resting close to the plasma membrane. This Ca2+ transient also triggered the transport of distant clusters of vesicles toward the plasma membrane. Upon exocytosis, the released serotonin activated autoreceptors coupled to phospholipase C, which in turn produced an intracellular Ca2+ increase in the submembrane shell. This localized Ca2+ increase evoked new exocytosis as the vesicles in the clusters arrived gradually at the plasma membrane. In this way, the extracellular serotonin elevated the intracellular Ca2+ and this Ca2+ evoked more exocytosis. The resulting positive feedback loop maintained exocytosis for the following hundreds of seconds until the last vesicles in the clusters fused. Since somatic exocytosis displays similar kinetics in neurons releasing different types of transmitters, the data presented here contributes to understand the cellular basis of paracrine neurotransmission. PMID:25018697

  8. A Voltage Controlled Oscillator for a Phase-Locked Loop Frequency Synthesizer in a Silicon-on-Sapphire Process

    SciTech Connect

    Garrison, Sean

    2009-05-21

    Engineers from a government-owned engineering and manufacturing facility were contracted by government-owned research laboratory to design and build an S-band telemetry transmitter using Radio Frequency Integrated Circuit (RFIC) technology packaged in a Low-Temperature Co-fired Ceramic (LTCC) Multi-Chip Module. The integrated circuit technology chosen for the Phase-Locked Loop Frequency Synthesizer portion of the telemetry transmitter was a 0.25 um CMOS process that utilizes a sapphire substrate and is fabricated by Peregrine Semiconductor corporation. This thesis work details the design of the Voltage Controlled Oscillator (VCO) portion of the PLL frequency synthesizer and constitutes an fully integrated VCO core circuit and a high-isolation buffer amplifier. The high-isolation buffer amplifier was designed to provide 16 dB of gain for 2200-3495 MHz as well as 60 dB of isolation for the oscillator core to provide immunity to frequency pulling due to RF load mismatch. Actual measurements of the amplifier gain and isolation showed the gain was approximately 5 dB lower than the simulated gain when all bond-wire and test substrate parasitics were taken into account. The isolation measurements were shown to be 28 dB at the high end of the frequency band but the measurement was more than likely compromised due to the aforementioned bond-wire and test substrate parasitics. The S-band oscillator discussed in this work was designed to operate over a frequency range of 2200 to 2300 MHz with a minimum output power of 0 dBm with a phase-noise of -92 dBc/Hz at a 100 kHz offset from the carrier. The tuning range was measured to be from 2215 MHz to 2330 MHz with a minimum output power of -7 dBm over the measured frequency range. A phase-noise of -90 dBc was measured at a 100 kHz offset from the carrier.

  9. Current-Sensing and Voltage-Feedback Driving Method for Large-Area High-Resolution Active Matrix Organic Light Emitting Diodes

    NASA Astrophysics Data System (ADS)

    In, Hai‑Jung; Choi, Byong‑Deok; Chung, Ho‑Kyoon; Kwon, Oh‑Kyong

    2006-05-01

    There is the problem of picture quality nonuniformity due to thin film transistor (TFT) characteristic variations throughout a panel of large-area high-resolution active matrix organic light emitting diodes. The current programming method could solve this issue, but it also requires very long charging time of a data line at low gray shades. Therefore, we propose a new driving method and a pixel circuit with emission-current sensing and feedback operation in order to resolve these problems. The proposed driving method and pixel circuit successfully compensate threshold voltage and mobility variations of TFTs and overcome the data line charging problem. Simulation results show that emission current deviations of the proposed driving method are less than 1.7% with ± 10.0% mobility and ± 0.3 V threshold voltage variations of pixel-driving TFTs, which means the proposed driving method is applicable to large-area high-resolution applications.

  10. A double-negative feedback loop between EZH2 and miR-26a regulates tumor cell growth in hepatocellular carcinoma.

    PubMed

    Zhuang, Chunbo; Wang, Pei; Huang, Da; Xu, Luming; Wang, Xiaobei; Wang, Lin; Hu, Lihua

    2016-03-01

    Accumulating evidence demonstrates the important roles of microRNAs (miRNAs) in tumor development and progression. miR-26a has been reported to be downregulated in several types of cancers including hepatocellular carcinoma, but the underlying mechanism of how miR-26a is repressed remains largely unknown. In the present study, we performed western blot analysis, qRT-PCR, luciferase reporter assay and chromatin immunoprecipitation assay to investigate the relationship between miR-26a and the enhancer of zest homologue 2 (EZH2). CCK-8 assay and colony formation assay were carried out to explore the effect of miR-26a on HCC cells proliferation. We demonstrated that miR-26a was epigenetically repressed by EZH2-mediated H3K27 trimethylation within the miR-26a promoter. Moreover, we confirmed that EZH2 was also a direct target of miR-26a in HCC cells, thus, creating a double-negative feedback loop. Furthermore, miR-26a restoration increased the expressions of its host genes (CTDSPL and CTDSP2). Overexpression of EZH2 abrogated miR-26a induction of CTDSPL and CTDSP2. Restoring the balance of the double-negative feedback loop by miR-26a overpression or EZH2 silence significantly inhibited HCC cell growth. Overexpression of EZH2 rescued the growth inhibition effect of miR-26a. These findings suggest that an imbalanced double-negative feedback loop between EZH2 and miR-26a exists in HCC cells, which contributes to miR-26a deregulation and regulates tumor cells proliferation. PMID:26781064

  11. Information Transfer in Gonadotropin-releasing Hormone (GnRH) Signaling: EXTRACELLULAR SIGNAL-REGULATED KINASE (ERK)-MEDIATED FEEDBACK LOOPS CONTROL HORMONE SENSING.

    PubMed

    Garner, Kathryn L; Perrett, Rebecca M; Voliotis, Margaritis; Bowsher, Clive; Pope, George R; Pham, Thanh; Caunt, Christopher J; Tsaneva-Atanasova, Krasimira; McArdle, Craig A

    2016-01-29

    Cell signaling pathways are noisy communication channels, and statistical measures derived from information theory can be used to quantify the information they transfer. Here we use single cell signaling measures to calculate mutual information as a measure of information transfer via gonadotropin-releasing hormone (GnRH) receptors (GnRHR) to extracellular signal-regulated kinase (ERK) or nuclear factor of activated T-cells (NFAT). This revealed mutual information values <1 bit, implying that individual GnRH-responsive cells cannot unambiguously differentiate even two equally probable input concentrations. Addressing possible mechanisms for mitigation of information loss, we focused on the ERK pathway and developed a stochastic activation model incorporating negative feedback and constitutive activity. Model simulations revealed interplay between fast (min) and slow (min-h) negative feedback loops with maximal information transfer at intermediate feedback levels. Consistent with this, experiments revealed that reducing negative feedback (by expressing catalytically inactive ERK2) and increasing negative feedback (by Egr1-driven expression of dual-specificity phosphatase 5 (DUSP5)) both reduced information transfer from GnRHR to ERK. It was also reduced by blocking protein synthesis (to prevent GnRH from increasing DUSP expression) but did not differ for different GnRHRs that do or do not undergo rapid homologous desensitization. Thus, the first statistical measures of information transfer via these receptors reveals that individual cells are unreliable sensors of GnRH concentration and that this reliability is maximal at intermediate levels of ERK-mediated negative feedback but is not influenced by receptor desensitization. PMID:26644469

  12. Closed-loop feedback control and bifurcation analysis of epileptiform activity via optogenetic stimulation in a mathematical model of human cortex

    NASA Astrophysics Data System (ADS)

    Selvaraj, Prashanth; Sleigh, Jamie W.; Kirsch, Heidi E.; Szeri, Andrew J.

    2016-01-01

    Optogenetics provides a method of neuron stimulation that has high spatial, temporal, and cell-type specificity. Here we present a model of optogenetic feedback control that targets the inhibitory population, which expresses light-sensitive channelrhodopsin-2 channels, in a mean-field model of undifferentiated cortex that is driven to seizures. The inhibitory population is illuminated with an intensity that is a function of electrode measurements obtained via the cortical model. We test the efficacy of this control method on seizurelike activity observed in two parameter spaces of the cortical model that most closely correspond to seizures observed in patients. We also compare the effect of closed-loop and open-loop control on seizurelike activity using a less-complicated ordinary differential equation model of the undifferentiated cortex in parameter space. Seizurelike activity is successfully suppressed in both parameter planes using optimal illumination intensities less likely to have adverse effects on cortical tissue.

  13. The Paracrine Feedback Loop Between Vitamin D3 (1,25(OH)2D3) and PTHrP in Prehypertrophic Chondrocytes

    PubMed Central

    Bach, Frances C; Rutten, Kirsten; Hendriks, Kristyanne; Riemers, Frank M; Cornelissen, Peter; de Bruin, Alain; Arkesteijn, Ger J; Wubbolts, Richard; Horton, William A; Penning, Louis C; Tryfonidou, Marianna A

    2014-01-01

    The endocrine feedback loop between vitamin D3 (1,25(OH)2D3) and parathyroid hormone (PTH) plays a central role in skeletal development. PTH-related protein (PTHrP) shares homology and its receptor (PTHR1) with PTH. The aim of this study was to investigate whether there is a functional paracrine feedback loop between 1,25(OH)2D3 and PTHrP in the growth plate, in parallel with the endocrine feedback loop between 1,25(OH)2D3 and PTH. This was investigated in ATDC5 cells treated with 10−8 M 1,25(OH)2D3 or PTHrP, Col2-pd2EGFP transgenic mice, and primary Col2-pd2EGFP growth plate chondrocytes isolated by FACS, using RT-qPCR, Western blot, PTHrP ELISA, chromatin immunoprecipitation (ChIP) assay, silencing of the 1,25(OH)2D3 receptor (VDR), immunofluorescent staining, immunohistochemistry, and histomorphometric analysis of the growth plate. The ChIP assay confirmed functional binding of the VDR to the PTHrP promoter, but not to the PTHR1 promoter. Treatment with 1,25(OH)2D3 decreased PTHrP protein production, an effect which was prevented by silencing of the VDR. Treatment with PTHrP significantly induced VDR production, but did not affect 1α- and 24-hydroxylase expression. Hypertrophic differentiation was inhibited by PTHrP and 1,25(OH)2D3 treatment. Taken together, these findings indicate that there is a functional paracrine feedback loop between 1,25(OH)2D3 and PTHrP in the growth plate. 1,25(OH)2D3 decreases PTHrP production, while PTHrP increases chondrocyte sensitivity to 1,25(OH)2D3 by increasing VDR production. In light of the role of 1,25(OH)2D3 and PTHrP in modulating chondrocyte differentiation, 1,25(OH)2D3 in addition to PTHrP could potentially be used to prevent undesirable hypertrophic chondrocyte differentiation during cartilage repair or regeneration. PMID:24777663

  14. The paracrine feedback loop between vitamin D₃ (1,25(OH)₂D₃) and PTHrP in prehypertrophic chondrocytes.

    PubMed

    Bach, Frances C; Rutten, Kirsten; Hendriks, Kristyanne; Riemers, Frank M; Cornelissen, Peter; de Bruin, Alain; Arkesteijn, Ger J; Wubbolts, Richard; Horton, William A; Penning, Louis C; Tryfonidou, Marianna A

    2014-12-01

    The endocrine feedback loop between vitamin D3(1,25(OH)2D3) and parathyroid hormone (PTH) plays a central role in skeletal development. PTH-related protein (PTHrP) shares homology and its receptor (PTHR1) with PTH. The aim of this study was to investigate whether there is a functional paracrine feedback loop between 1,25(OH)2D3 and PTHrP in the growth plate, in parallel with the endocrine feedback loop between 1,25(OH)2D3 and PTH. This was investigated in ATDC5 cells treated with 10(-8) M 1,25(OH)2D3 or PTHrP, Col2-pd2EGFP transgenic mice, and primary Col2-pd2EGFP growth plate chondrocytes isolated by FACS, using RT-qPCR, Western blot, PTHrP ELISA, chromatin immunoprecipitation (ChIP) assay, silencing of the 1,25(OH)2D3 receptor (VDR), immunofluorescent staining, immunohistochemistry, and histomorphometric analysis of the growth plate. The ChIP assay confirmed functional binding of the VDR to the PTHrP promoter, but not to the PTHR1 promoter. Treatment with 1,25(OH)2D3 decreased PTHrP protein production, an effect which was prevented by silencing of the VDR. Treatment with PTHrP significantly induced VDR production, but did not affect 1α- and 24-hydroxylase expression. Hypertrophic differentiation was inhibited by PTHrP and 1,25(OH)2D3 treatment. Taken together, these findings indicate that there is a functional paracrine feedback loop between 1,25(OH)2D3 and PTHrP in the growth plate. 1,25(OH)2D3 decreases PTHrP production, while PTHrP increases chondrocyte sensitivity to 1,25(OH)2D3 by increasing VDR production. In light of the role of 1,25(OH)2D3 and PTHrP in modulating chondrocyte differentiation, 1,25(OH)2D3 in addition to PTHrP could potentially be used to prevent undesirable hypertrophic chondrocyte differentiation during cartilage repair or regeneration. PMID:24777663

  15. Robust Voltage Stabilization in an Isolated Wind-Diesel Power System using PSO based-Fixed Structure H∞ Loop Shaping Control

    NASA Astrophysics Data System (ADS)

    Vachirasricirikul, Sitthidet; Ngamroo, Issarachai; Kaitwanidvilai, Somyot

    It is well known that the power system controller designed by H∞ control is complicated, high order and impractical. In power system applications, practical structures such as proportional integral derivative (PID) etc., are widely used, because of their simple structure, less number of tuning parameters and low-order. However, tuning of controller parameters to achieve a good performance and robustness is based on designer's experiences. To overcome this problem, this paper proposes a fixed structure robust H∞ loop shaping control to design Static Var Compensator (SVC) and Automatic Voltage Regulator (AVR) for robust stabilization of voltage fluctuation in an isolated wind-diesel hybrid power system. The structure of the robust controller of SVC and AVR is specified by a PID controller. In the system modeling, a normalized coprime factorization is applied to represent possible unstructured uncertainties in the power system such as variation of system parameters, generating and loading conditions etc. Based on the H∞ loop shaping, the performance and robust stability conditions are formulated as the optimization problem. The particle swarm optimization is applied to solve for PID control parameters of SVC and AVR simultaneously. Simulation studies confirm the control effect and robustness of the proposed control.

  16. A neural mass model with direct and indirect excitatory feedback loops: identification of bifurcations and temporal dynamics.

    PubMed

    Garnier, Aurélie; Vidal, Alexandre; Huneau, Clément; Benali, Habib

    2015-02-01

    Neural mass modeling is a part of computational neuroscience that was developed to study the general behavior of a neuronal population. This type of mesoscopic model is able to generate output signals that are comparable to experimental data, such as electroencephalograms. Classically, neural mass models consider two interconnected populations: excitatory pyramidal cells and inhibitory interneurons. However, many authors have included an excitatory feedback on the pyramidal cell population. Two distinct approaches have been developed: a direct feedback on the main pyramidal cell population and an indirect feedback via a secondary pyramidal cell population. In this letter, we propose a new neural mass model that couples these two approaches. We perform a detailed bifurcation analysis and present a glossary of dynamical behaviors and associated time series. Our study reveals that the model is able to generate particular realistic time series that were never pointed out in either simulated or experimental data. Finally, we aim to evaluate the effect of balance between both excitatory feedbacks on the dynamical behavior of the model. For this purpose, we compute the codimension 2 bifurcation diagrams of the system to establish a map of the repartition of dynamical behaviors in a direct versus indirect feedback parameter space. A perspective of this work is, from a given temporal series, to estimate the parameter value range, especially in terms of direct versus indirect excitatory feedback. PMID:25514111

  17. DISTRIBUTED AMPLIFIER INCORPORATING FEEDBACK

    DOEpatents

    Bell, P.R. Jr.

    1958-10-21

    An improved distributed amplifier system employing feedback for stabilization is presented. In accordance with the disclosed invention, a signal to be amplified is applled to one end of a suitable terminated grid transmission line. At intervals along the transmission line, the signal is fed to stable, resistance-capacitance coupled amplifiers incorporating feedback loops therein. The output current from each amplifier is passed through an additional tube to minimize the electrostatic capacitance between the tube elements of the last stage of the amplifier, and fed to appropriate points on an output transmission line, similar to the grid line, but terminated at the opposite (input) end. The output taken from the unterminated end of the plate transmission line is proportional to the input voltage impressed upon the grid line.

  18. Selectivity filters and cysteine-rich extracellular loops in voltage-gated sodium, calcium, and NALCN channels

    PubMed Central

    Stephens, Robert F.; Guan, W.; Zhorov, Boris S.; Spafford, J. David

    2015-01-01

    How nature discriminates sodium from calcium ions in eukaryotic channels has been difficult to resolve because they contain four homologous, but markedly different repeat domains. We glean clues from analyzing the changing pore region in sodium, calcium and NALCN channels, from single-cell eukaryotes to mammals. Alternative splicing in invertebrate homologs provides insights into different structural features underlying calcium and sodium selectivity. NALCN generates alternative ion selectivity with splicing that changes the high field strength (HFS) site at the narrowest level of the hourglass shaped pore where the selectivity filter is located. Alternative splicing creates NALCN isoforms, in which the HFS site has a ring of glutamates contributed by all four repeat domains (EEEE), or three glutamates and a lysine residue in the third (EEKE) or second (EKEE) position. Alternative splicing provides sodium and/or calcium selectivity in T-type channels with extracellular loops between S5 and P-helices (S5P) of different lengths that contain three or five cysteines. All eukaryotic channels have a set of eight core cysteines in extracellular regions, but the T-type channels have an infusion of 4–12 extra cysteines in extracellular regions. The pattern of conservation suggests a possible pairing of long loops in Domains I and III, which are bridged with core cysteines in NALCN, Cav, and Nav channels, and pairing of shorter loops in Domains II and IV in T-type channel through disulfide bonds involving T-type specific cysteines. Extracellular turrets of increasing lengths in potassium channels (Kir2.2, hERG, and K2P1) contribute to a changing landscape above the pore selectivity filter that can limit drug access and serve as an ion pre-filter before ions reach the pore selectivity filter below. Pairing of extended loops likely contributes to the large extracellular appendage as seen in single particle electron cryo-microscopy images of the eel Nav1 channel. PMID:26042044

  19. PTEN deficiency is associated with reduced sensitivity to mTOR inhibitor in human bladder cancer through the unhampered feedback loop driving PI3K/Akt activation

    PubMed Central

    Seront, E; Pinto, A; Bouzin, C; Bertrand, L; Machiels, J-P; Feron, O

    2013-01-01

    Background: Preclinical studies have shown that PTEN loss enhances sensitivity to mammalian target of Rapamycin (mTOR) inhibitors because of facilitated PI3K (phosphatidylinositol-3 kinase)/Akt activation and consecutive stimulation of the mTOR pathway. In patients with advanced transitional cell carcinoma (TCC) treated with the mTOR inhibitor everolimus, PTEN loss was, however, associated with resistance to treatment. Methods: Transitional cell carcinoma specimens, human bladder cancer cells and derived mouse xenografts were used to evaluate how the PTEN status influences the activity of mTOR inhibitors. Results: Transitional cell carcinoma patients with a shorter progression-free survival under everolimus exhibited PTEN deficiency and increased Akt activation. Moreover, PTEN-deficient bladder cancer cells were less sensitive to rapamycin than cells expressing wild-type PTEN, and rapamycin strikingly induced Akt activation in the absence of functional PTEN. Inhibition of Akt activation by the PI3K inhibitor wortmannin interrupted this rapamycin-induced feedback loop, thereby enhancing the antiproliferative effects of the mTOR inhibitor both in vitro and in vivo. Conclusion: Facilitation of Akt activation upon PTEN loss can have a more prominent role in driving the feedback loop in response to mTOR inhibition than in promoting the mTOR pathway. These data support the use of both PI3K and mTOR inhibitors to treat urothelial carcinoma, in particular in the absence of functional PTEN. PMID:23989949

  20. miR-29ab1-deficiency Identifies a Negative Feedback Loop Controlling Th1 Bias that is Dysregulated in Multiple Sclerosis1

    PubMed Central

    Smith, Kristen M.; Guerau-de-Arellano, Mireia; Costinean, Stefan; Williams, Jessica L.; Bottoni, Arianna; Cox, Gina Mavrikis; Satoskar, Abhay R.; Croce, Carlo M.; Racke, Michael K.; Lovett-Racke, Amy E.; Whitacre, Caroline C.

    2012-01-01

    T-helper cell programming and function is tightly regulated by complex biological networks to prevent excessive inflammatory responses and autoimmune disease. The importance of miRNAs in this process is highlighted by the preferential Th1 polarization of Dicer-deficient T cells that lack miRNAs. Using genetic knockouts, we demonstrate that loss of endogenous miR-29, derived from the miR-29ab1 genomic cluster, results in unrestrained T-bet expression and IFN-γ production. miR-29b regulates T-bet and IFN-γ via a direct interaction with the 3′UTRs, and IFN-γ itself enhances miR-29b expression, establishing a novel regulatory feedback loop. miR-29b is increased in memory CD4+ T cells from multiple sclerosis (MS) patients, which may reflect chronic Th1 inflammation. However, miR-29b levels decrease significantly upon T cell activation in MS patients, suggesting that this feedback loop is dysregulated in MS patients and may contribute to chronic inflammation. miR-29 thus serves as a novel regulator of Th1 differentiation, adding to the understanding of T cell-intrinsic regulatory mechanisms that maintain a balance between protective immunity and autoimmunity. PMID:22772450

  1. Microgyroscope with closed loop output

    NASA Technical Reports Server (NTRS)

    Challoner, A. Dorian (Inventor); Gutierrez, Roman C. (Inventor); Tang, Tony K. (Inventor); Cargille, Donald R. (Inventor)

    2002-01-01

    A micro-gyroscope (10) having closed loop operation by a control voltage (V.sub.TY), that is demodulated by an output signal of the sense electrodes (S1, S2), providing Coriolis torque rebalance to prevent displacement of the micro-gyroscope (10) on the output axis (y-axis). The present invention provides wide-band, closed-loop operation for a micro-gyroscope (10) and allows the drive frequency to be closely tuned to a high Q sense axis resonance. A differential sense signal (S1-S2) is compensated and fed back by differentially changing the voltage on the drive electrodes to rebalance Coriolis torque. The feedback signal is demodulated in phase with the drive axis signal (K.sub..omega..crclbar..sub.x) to produce a measure of the Coriolis force.

  2. Application of a Virtual Reactivity Feedback Control Loop in Non-Nuclear Testing of a Fast Spectrum Reactor

    NASA Technical Reports Server (NTRS)

    Bragg-Sitton, Shannon M.; Forsbacka, Matthew

    2004-01-01

    For a compact, fast-spectrum reactor, reactivity feedback is dominated by core deformation at elevated temperature. Given the use of accurate deformation measurement techniques, it is possible to simulate nuclear feedback in non-nuclear electrically heated reactor tests. Implementation of simulated reactivity feedback in response to measured deflection is being tested at the NASA Marshall Space Flight Center Early Flight Fission Test Facility (EFF-TF). During tests of the SAFE-100 reactor prototype, core deflection was monitored using a high resolution camera. "virtual" reactivity feedback was accomplished by applying the results of Monte Carlo calculations (MCNPX) to core deflection measurements; the computational analysis was used to establish the reactivity worth of van'ous core deformations. The power delivered to the SAFE-100 prototype was then dusted accordingly via kinetics calculations, The work presented in this paper will demonstrate virtual reactivity feedback as core power was increased from 1 kilowatt(sub t), to 10 kilowatts(sub t), held approximately constant at 10 kilowatts (sub t), and then allowed to decrease based on the negative thermal reactivity coefficient.

  3. The feedback loop between miR-124 and TGF-β pathway plays a significant role in non-small cell lung cancer metastasis.

    PubMed

    Zu, Lidong; Xue, Yunjing; Wang, Jinglong; Fu, Yujie; Wang, Xiumin; Xiao, Gang; Hao, Mingang; Sun, Xueqing; Wang, Yingying; Fu, Guohui; Wang, Jianhua

    2016-03-01

    Increasing evidence shows that micro RNAs (miRNAs) play a critical role in tumor development. However, the role of miRNAs in non-small cell lung cancer (NSCLC) metastasis remains largely unknown. Here, we found that miR-124 expression was significantly impaired in NSCLC tissues and associated with its metastasis. In vitro and in vivo experiments indicate that restoring miR-124 expression in NSCLC cells had a marked effect on reducing cell migration, invasion and metastasis. Mechanistic analyses show that Smad4, a cobinding protein in transforming growth factor-β (TGF-β) pathway, was identified as a new target gene of miR-124. Restoring Smad4 expression in miR-124-infected cells could partially rescue miR-124-induced abolition of cell migration and invasion. Notably, upon TGF-β stimulation, phosphorylation of Smad2/3 was modulated by alteration of miR-124 or Smad4 expression, followed by inducing some special transcription of downstream genes including Snail, Slug and ZEB2, all of which may trigger epithelial-mesenchymal transition and be associated with NSCLC metastasis. Moreover, activation of TGF-β pathway may enhance expression of DNMT3a, leading to hypermethylation on miR-124 promoter. Therefore, heavily loss of miR-124 expression further enhances Smad4 level by this feedback loop. Taken together, our data show for the first time that the feedback loop between miR-124 and TGF-β pathway may play a significant role in NSCLC metastasis. Targeting the loop may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for NSCLC. PMID:26818357

  4. Stochasticity and bifurcations in a reduced model with interlinked positive and negative feedback loops of CREB1 and CREB2 stimulated by 5-HT.

    PubMed

    Hao, Lijie; Yang, Zhuoqin; Bi, Yuanhong

    2016-04-01

    The cyclic AMP (cAMP)-response element-binding protein (CREB) family of transcription factors is crucial in regulating gene expression required for long-term memory (LTM) formation. Upon exposure of sensory neurons to the neurotransmitter serotonin (5-HT), CREB1 is activated via activation of the protein kinase A (PKA) intracellular signaling pathways, and CREB2 as a transcriptional repressor is relieved possibly via phosphorylation of CREB2 by mitogen-activated protein kinase (MAPK). Song et al. [18] proposed a minimal model with only interlinked positive and negative feedback loops of transcriptional regulation by the activator CREB1 and the repressor CREB2. Without considering feedbacks between the CREB proteins, Pettigrew et al. [8] developed a computational model characterizing complex dynamics of biochemical pathways downstream of 5-HT receptors. In this work, to describe more simply the biochemical pathways and gene regulation underlying 5-HT-induced LTM, we add the important extracellular sensitizing stimulus 5-HT as well as the product Ap-uch into the Song's minimal model. We also strive to examine dynamical properties of the gene regulatory network under the changing concentration of the stimulus, [5-HT], cooperating with the varying positive feedback strength in inducing a high state of CREB1 for the establishment of long-term memory. Different dynamics including monostability, bistability and multistability due to coexistence of stable steady states and oscillations is investigated by means of codimension-2 bifurcation analysis. At the different positive feedback strengths, comparative analysis of deterministic and stochastic dynamics reveals that codimension-1 bifurcation with respect to [5-HT] as the parameter can predict diverse stochastic behaviors resulted from the finite number of molecules, and the number of CREB1 molecules more and more preferentially resides near the high steady state with increasing [5-HT], which contributes to long-term memory formation. PMID:26877074

  5. A negative feedback loop that limits the ectopic activation of a cell type-specific sporulation sigma factor of Bacillus subtilis.

    PubMed

    Serrano, Mónica; Real, Gonçalo; Santos, Joana; Carneiro, Jorge; Moran, Charles P; Henriques, Adriano O

    2011-09-01

    Two highly similar RNA polymerase sigma subunits, σ(F) and σ(G), govern the early and late phases of forespore-specific gene expression during spore differentiation in Bacillus subtilis. σ(F) drives synthesis of σ(G) but the latter only becomes active once engulfment of the forespore by the mother cell is completed, its levels rising quickly due to a positive feedback loop. The mechanisms that prevent premature or ectopic activation of σ(G) while discriminating between σ(F) and σ(G) in the forespore are not fully comprehended. Here, we report that the substitution of an asparagine by a glutamic acid at position 45 of σ(G) (N45E) strongly reduced binding by a previously characterized anti-sigma factor, CsfB (also known as Gin), in vitro, and increased the activity of σ(G) in vivo. The N45E mutation caused the appearance of a sub-population of pre-divisional cells with strong activity of σ(G). CsfB is normally produced in the forespore, under σ(F) control, but sigGN45E mutant cells also expressed csfB and did so in a σ(G)-dependent manner, autonomously from σ(F). Thus, a negative feedback loop involving CsfB counteracts the positive feedback loop resulting from ectopic σ(G) activity. N45 is invariant in the homologous position of σ(G) orthologues, whereas its functional equivalent in σ(F) proteins, E39, is highly conserved. While CsfB does not bind to wild-type σ(F), a E39N substitution in σ(F) resulted in efficient binding of CsfB to σ(F). Moreover, under certain conditions, the E39N alteration strongly restrains the activity of σ(F) in vivo, in a csfB-dependent manner, and the efficiency of sporulation. Therefore, a single amino residue, N45/E39, is sufficient for the ability of CsfB to discriminate between the two forespore-specific sigma factors in B. subtilis. PMID:21935351

  6. High voltage DC power supply

    DOEpatents

    Droege, T.F.

    1989-12-19

    A high voltage DC power supply having a first series resistor at the output for limiting current in the event of a short-circuited output, a second series resistor for sensing the magnitude of output current, and a voltage divider circuit for providing a source of feedback voltage for use in voltage regulation is disclosed. The voltage divider circuit is coupled to the second series resistor so as to compensate the feedback voltage for a voltage drop across the first series resistor. The power supply also includes a pulse-width modulated control circuit, having dual clock signals, which is responsive to both the feedback voltage and a command voltage, and also includes voltage and current measuring circuits responsive to the feedback voltage and the voltage developed across the second series resistor respectively. 7 figs.

  7. High voltage DC power supply

    DOEpatents

    Droege, Thomas F.

    1989-01-01

    A high voltage DC power supply having a first series resistor at the output for limiting current in the event of a short-circuited output, a second series resistor for sensing the magnitude of output current, and a voltage divider circuit for providing a source of feedback voltage for use in voltage regulation is disclosed. The voltage divider circuit is coupled to the second series resistor so as to compensate the feedback voltage for a voltage drop across the first series resistor. The power supply also includes a pulse-width modulated control circuit, having dual clock signals, which is responsive to both the feedback voltage and a command voltage, and also includes voltage and current measuring circuits responsive to the feedback voltage and the voltage developed across the second series resistor respectively.

  8. Digital phase-locked-loop speed sensor for accuracy improvement in analog speed controls. [feedback control and integrated circuits

    NASA Technical Reports Server (NTRS)

    Birchenough, A. G.

    1975-01-01

    A digital speed control that can be combined with a proportional analog controller is described. The stability and transient response of the analog controller were retained and combined with the long-term accuracy of a crystal-controlled integral controller. A relatively simple circuit was developed by using phase-locked-loop techniques and total error storage. The integral digital controller will maintain speed control accuracy equal to that of the crystal reference oscillator.

  9. Obg-like ATPase 1 regulates global protein serine/threonine phosphorylation in cancer cells by suppressing the GSK3β-inhibitor 2-PP1 positive feedback loop

    PubMed Central

    Xu, Dong; Song, Renduo; Wang, Guohui; Jeyabal, Prince V.S.; Weiskoff, Amanda M.; Ding, Kefeng; Shi, Zheng-Zheng

    2016-01-01

    OLA1 is an Obg family P-loop NTPase that possesses both GTP- and ATP-hydrolyzing activities. Here we report that OLA1 is a GSK3β interacting protein, and through its ATPase activity, inhibits the GSK3β-mediated activation of protein serine/threonine phosphatase 1 (PP1). It is hypothesized that GSK3β phosphorylates inhibitor 2 (I-2) of PP1 at Thr-72 and activates the PP1 · I-2 complex, which in turn dephosphorylates and stimulates GSK3β, thus forming a positive feedback loop. We revealed that the positive feedback loop is normally suppressed by OLA1, and becomes over-activated under OLA1 deficiency, resulting in increased cellular PP1 activity and dephosphorylation of multiple Ser/Thr phosphoproteins, and more strikingly, decreased global protein threonine phosphorylation. Furthermore, using xenograft models of colon cancer (H116) and ovarian cancer (SKOV3), we established a correlation among downregulation of OLA1, over-activation of the positive feedback loop as indicated by under-phosphorylation of I-2, and more aggressive tumor growth. This study provides the first evidence for the existence of a GSK3β-I-2-PP1 positive feedback loop in human cancer cells, and identifies OLA1 as an endogenous suppressor of this signaling motif. PMID:26655089

  10. Obg-like ATPase 1 regulates global protein serine/threonine phosphorylation in cancer cells by suppressing the GSK3β-inhibitor 2-PP1 positive feedback loop.

    PubMed

    Xu, Dong; Song, Renduo; Wang, Guohui; Jeyabal, Prince V S; Weiskoff, Amanda M; Ding, Kefeng; Shi, Zheng-Zheng

    2016-01-19

    OLA1 is an Obg family P-loop NTPase that possesses both GTP- and ATP-hydrolyzing activities. Here we report that OLA1 is a GSK3β interacting protein, and through its ATPase activity, inhibits the GSK3β-mediated activation of protein serine/threonine phosphatase 1 (PP1). It is hypothesized that GSK3β phosphorylates inhibitor 2 (I-2) of PP1 at Thr-72 and activates the PP1 · I-2 complex, which in turn dephosphorylates and stimulates GSK3β, thus forming a positive feedback loop. We revealed that the positive feedback loop is normally suppressed by OLA1, and becomes over-activated under OLA1 deficiency, resulting in increased cellular PP1 activity and dephosphorylation of multiple Ser/Thr phosphoproteins, and more strikingly, decreased global protein threonine phosphorylation. Furthermore, using xenograft models of colon cancer (H116) and ovarian cancer (SKOV3), we established a correlation among downregulation of OLA1, over-activation of the positive feedback loop as indicated by under-phosphorylation of I-2, and more aggressive tumor growth. This study provides the first evidence for the existence of a GSK3β-I-2-PP1 positive feedback loop in human cancer cells, and identifies OLA1 as an endogenous suppressor of this signaling motif. PMID:26655089

  11. An analog RF gap voltage regulation system for the Advanced Photon Source storage ring.

    SciTech Connect

    Horan, D.

    1999-04-13

    An analog rf gap voltage regulation system has been designed and built at Argonne National Laboratory to maintain constant total storage ring rf gap voltage, independent of beam loading and cavity tuning effects. The design uses feedback control of the klystron mod-anode voltage to vary the amount of rf power fed to the storage ring cavities. The system consists of two independent feedback loops, each regulating the combined rf gap voltages of eight storage ring cavities by varying the output power of either one or two rf stations, depending on the mode of operation. It provides full operator control and permissive logic to permit feedback control of the rf system output power only if proper conditions are met. The feedback system uses envelope-detected cavity field probe outputs as the feedback signal. Two different methods of combining the individual field probe signals were used to generate a relative DC level representing one-half of the total storage ring rf voltage, an envelope-detected vector sum of the field probe rf signals, and the DC sum of individual field probe envelope detector outputs. The merits of both methods are discussed. The klystron high-voltage power supply (HVPS) units are fitted with an analog interface for external control of the mod-anode voltage level, using a four-quadrant analog multiplier to modulate the HVPS mod-anode voltage regulator set-point in response to feedback system commands.

  12. Sox2 Expression Is Regulated by a Negative Feedback Loop in Embryonic Stem Cells That Involves AKT Signaling and FoxO1

    PubMed Central

    Rizzino, Angie

    2013-01-01

    The self-renewal and pluripotency of embryonic stem cells (ESC) is regulated by a highly integrated network of essential transcription factors, which includes Sox2. Previous studies have shown that elevating Sox2 on its own in mouse ESC induces differentiation and inhibits the expression of endogenous Sox2 at the protein and mRNA level. These findings led us to hypothesize that increases in Sox2 activate a negative feedback loop that inhibits the transcription of the endogenous Sox2 gene. To test this hypothesis, we used i-OSKM-ESC, which elevate Sox2 in conjunction with Oct4, Klf4, and c-Myc when treated with doxycycline (Dox). Elevating the expression of these four transcription factors in i-OSKM-ESC does not induce differentiation, but it represses expression of endogenous Sox2. We determined that increases of Sox2 in i-OSKM-ESC lead to increases in activated AKT and inactivation of FoxO1 (an activator of Sox2), as well as decreases in binding of FoxO1 to the 5'flanking region of Sox2. Importantly, we determined that inhibition of AKT in Dox-treated i-OSKM-ESC leads to re-expression of endogenous Sox2 at the mRNA and protein level and reactivation of FoxO1. These findings argue that AKT signaling is part of the negative feedback loop that helps carefully control the transcription of Sox2 in ESC by modulating the binding of FoxO1 to the Sox2 gene. Collectively, our findings provide new insights into the mechanisms that enable ESC to carefully regulate the levels of Sox2 and retain their stem cell properties. PMID:24116102

  13. Pin1, endothelial nitric oxide synthase, and amyloid-β form a feedback signaling loop involved in the pathogenesis of Alzheimer's disease, hypertension, and cerebral amyloid angiopathy.

    PubMed

    Wang, Jing-Zhang; Zhu, Wang-Dong; Xu, Zhong-Xin; Du, Wen-Tao; Zhang, Hong-Yan; Sun, Xue-Wen; Wang, Xiao-Hua

    2014-02-01

    Although the molecular mechanism has not yet been clarified until now, it is very interesting that Alzheimer's disease (AD), hypertension (HTN), and cerebral amyloid angiopathy (CAA) often occur synchronously and possess many similar pathological characteristics. Herein, we hypothesize that a feedback signaling loop, consisted of Pin1, endothelial nitric oxide synthase (eNOS), and amyloid-β (Aβ), may contribute to the interesting pathological phenomenon. First, Pin1 inhibits the production of Aβ, and enhances the activity of eNOS. Second, Aβ and eNOS form a mutual inhibition system. Third, the well-balanced feedback signaling loop avoids the development of AD, HTN, and CAA by inhibiting the frequent pathological characteristics of these diseases, including Aβ deposition in cerebral microvessels and cerebral microbleeds. On one hand, Pin1 and eNOS not only inhibit Aβ production but also accelerate Aβ clearance, preventing Aβ deposition in cerebral microvessels. On the other hand, Pin1 and eNOS promote vasodilatation and prevent the elevation of blood pressure in brain, alleviating the pathology of cerebral microbleeds. However, once the precise balance is disturbed, it may result in Aβ deposition, microbleeds, and elevated blood pressure, possibly leading to the synchronous occurrence of AD, HTN, and CAA. The hypothesis updates the current understanding of the molecular linkage among AD, HTN, and CAA, and lays the ground for developing combined prevention, diagnosis, and treatment of these diseases more efficiently and more economically. Interestingly, biotechnical medicines enhancing the activity of Pin1 and/or eNOS may prevent the development of AD, HTN, and CAA, and targeting Aβ deposition may alleviate the clinical pathologies of these related diseases. PMID:24332564

  14. REG3A accelerates pancreatic cancer cell growth under IL-6-associated inflammatory condition: Involvement of a REG3A-JAK2/STAT3 positive feedback loop.

    PubMed

    Liu, Xiulan; Wang, Jun; Wang, Hongjie; Yin, Guoxiao; Liu, Yang; Lei, Xiang; Xiang, Ming

    2015-06-28

    Regenerating gene protein (REG) 3A is a 19 kD secretory pancreas protein with pro-growth function. Previously we demonstrated that overexpression of REG3A, acting as a key molecule for up-regulation of the JAK2/STAT3 pathway, contributed to inflammation-related pancreatic cancer (PaC) development. However the exact network associated with REG3A signaling still remains unclear. Here we determined that exposure of human PaC cells to cytokine IL-6 activated the oncogenic JAK2/STAT3 pathway, which directly upregulated REG3A expression, accelerated cell cycle progression by promoting CyclinD1 expression, and enhancing the expression of the anti-apoptosis Bcl family. Importantly, the activation of REG3A would instead enhance the JAK2/STAT3 pathway to constitute a REG3A-JAK2/STAT3 positive feedback loop, which leads to the amplification of the oncogenic effects of IL-6/JAK2/STAT3, a classic pathway linking to inflammation-related tumorigenesis, ultimately resulting in PaC cell over-proliferation and tumor formation both in vitro and in vivo. Moreover, EGFR was found to mediate the REG3A signal for PaC cell growth and JAK2/STAT3 activation, thus functioning as a REG3A receptor. Collectively, our results provide the first evidence for the presence of the synergistic effect of REG3A and IL-6 on PaC development via a REG3A-JAK2/STAT3 positive feedback loop. PMID:25779676

  15. Pilot-in-the-Loop Evaluation of a Yaw Rate to Throttle Feedback Control with Enhanced Engine Response

    NASA Technical Reports Server (NTRS)

    Litt, Jonathan S.; Guo, Ten-Huei; Sowers, T. Shane; Chicatelli, Amy K.; Fulton, Christopher E.; May, Ryan D.; Owen, A. Karl

    2012-01-01

    This paper describes the implementation and evaluation of a yaw rate to throttle feedback system designed to replace a damaged rudder. It can act as a Dutch roll damper and as a means to facilitate pilot input for crosswind landings. Enhanced propulsion control modes were implemented to increase responsiveness and thrust level of the engine, which impact flight dynamics and performance. Piloted evaluations were performed to determine the capability of the engines to substitute for the rudder function under emergency conditions. The results showed that this type of implementation is beneficial, but the engines' capability to replace the rudder is limited.

  16. High Power Passive Phase Locking of Four Yb-Doped Fiber Amplifiers by an All-Optical Feedback Loop

    NASA Astrophysics Data System (ADS)

    Xue, Yu-Hao; He, Bing; Zhou, Jun; Li, Zhen; Fan, Yuan-Yuan; Qi, Yun-Feng; Liu, Chi; Yuan, Zhi-Jun; Zhang, Hai-Bo; Lou, Qi-Hong

    2011-05-01

    We report the passive phase locking of four high power Yb-doped fiber amplifiers with ring cavity. The interference patterns at different output power are observed and the Strehl ratios are measured. The maximum coherent output power of the fiber array is up to 1062 W by multi-stage amplification. The stable beam profiles of various phase relationships are observed by controlling the position of the feedback fiber, in good agreement with the calculated results. By using master oscillator power-amplifier (MOPA) architecture and broadband operation of passively phased systems, higher power scaling with high beam quality appears to be feasible.

  17. Control algorithm for the inverter fed induction motor drive with DC current feedback loop based on principles of the vector control

    SciTech Connect

    Vuckovic, V.; Vukosavic, S. )

    1992-01-01

    This paper brings out a control algorithm for VSI fed induction motor drives based on the converter DC link current feedback. It is shown that the speed and flux can be controlled over the wide speed and load range quite satisfactorily for simpler drives. The base commands of both the inverter voltage and frequency are proportional to the reference speed, but each of them is further modified by the signals derived from the DC current sensor. The algorithm is based on the equations well known from the vector control theory, and is aimed to obtain the constant rotor flux and proportionality between the electrical torque, the slip frequency and the active component of the stator current. In this way, the problems of slip compensation, Ri compensation and correction of U/f characteristics are solved in the same time. Analytical considerations and computer simulations of the proposed control structure are in close agreement with the experimental results measured on a prototype drive.

  18. Hybrid wide-band, low-phase-noise scheme for Raman lasers in atom interferometry by integrating an acousto-optic modulator and a feedback loop.

    PubMed

    Wang, Kai; Yao, Zhanwei; Li, Runbing; Lu, Sibin; Chen, Xi; Wang, Jin; Zhan, Mingsheng

    2016-02-10

    We report a hybrid scheme for phase-coherent Raman lasers with low phase noise in a wide frequency range. In this scheme, a pair of Raman lasers with a frequency difference of 3.04 GHz is generated by the ±1-order diffracted lights of an acousto-optic modulator (1.52 GHz), where a feedback loop is simultaneously applied for suppressing the phase noise. The beat width of the Raman lasers is narrower than 3 Hz. In the low-frequency range, the phase noise of the Raman lasers is suppressed by 35 dB with the feedback. The phase noise is less than -109  dBc/Hz in the high-frequency range. The sensitivity of an atom gyroscope employing the hybrid Raman lasers can be implicitly improved 10 times. Due to the better high-frequency response, the sensitivity is not limited by the durations of Raman pulses. This work is important for improving the performance of atom-interferometer-based measurements. PMID:26906364

  19. Derivation of three closed loop kinematic velocity models using normalized quaternion feedback for an autonomous redundant manipulator with application to inverse kinematics

    SciTech Connect

    Unseren, M.A.

    1993-04-01

    The report discusses the orientation tracking control problem for a kinematically redundant, autonomous manipulator moving in a three dimensional workspace. The orientation error is derived using the normalized quaternion error method of Ickes, the Luh, Walker, and Paul error method, and a method suggested here utilizing the Rodrigues parameters, all of which are expressed in terms of normalized quaternions. The analytical time derivatives of the orientation errors are determined. The latter, along with the translational velocity error, form a dosed loop kinematic velocity model of the manipulator using normalized quaternion and translational position feedback. An analysis of the singularities associated with expressing the models in a form suitable for solving the inverse kinematics problem is given. Two redundancy resolution algorithms originally developed using an open loop kinematic velocity model of the manipulator are extended to properly take into account the orientation tracking control problem. This report furnishes the necessary mathematical framework required prior to experimental implementation of the orientation tracking control schemes on the seven axis CESARm research manipulator or on the seven-axis Robotics Research K1207i dexterous manipulator, the latter of which is to be delivered to the Oak Ridge National Laboratory in 1993.

  20. FoxM1 promotes breast tumorigenesis by activating PDGF-A and forming a positive feedback loop with the PDGF/AKT signaling pathway.

    PubMed

    Yu, Guanzhen; Zhou, Aidong; Xue, Jianfei; Huang, Chen; Zhang, Xia; Kang, Shin-Hyuk; Chiu, Wen-Tai; Tan, Christina; Xie, Keping; Wang, Jiejun; Huang, Suyun

    2015-05-10

    The autocrine platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) signaling pathway promotes breast cancer tumorigenesis, but the mechanisms for its dysregulation in breast cancer are largely unknown. In the study, we identified PDGF-A as a novel transcriptional target of FoxM1. FoxM1 directly binds to two sites in the promoter of PDGF-A and activates its transcription. Mutation of these FoxM1-binding sites diminished PDGF-A promoter activity. Increased FoxM1 resulted in the upregulation of PDGF-A, which led to activation of the AKT pathway and increased breast cancer cell proliferation and tumorigenesis, whereas knockdown of FoxM1 does the opposite. Blocking AKT activation with a phosphoinositide 3-kinase/AKT inhibitor decreased FoxM1-induced cell proliferation. Moreover, PDGF/AKT pathway upregulates the expression of FoxM1 in breast cancer cells. Knockdown of PDGF-A or blockade of AKT activation inhibited the expression of FoxM1 in breast cancer cells. Furthermore, expression of FoxM1 significantly correlated with the expression of PDGF-A and the activated AKT signaling pathway in human breast cancer specimens. Our study demonstrates a novel positive regulatory feedback loop between FoxM1 and the PDGF/AKT signaling pathway; this loop contributes to breast cancer cell growth and tumorigenesis. PMID:25869208

  1. A feedback regulatory loop involving p53/miR-200 and growth hormone endocrine axis controls embryo size of zebrafish

    PubMed Central

    Jing, Jing; Xiong, Shuting; Li, Zhi; Wu, Junjie; Zhou, Li; Gui, Jian-Fang; Mei, Jie

    2015-01-01

    In vertebrates, growth hormone/insulin-like growth factor (GH/IGF) axis signaling plays a critical role in regulating somatic growth. Understanding the direct upstream regulators of GH/IGF axis remains a major challenge. Our studies of the zebrafish reveal that the conserved miR-200 family members are critical regulators of embryo size by targeting several GH/IGF axis genes, including GH, GHRa, GHRb and IGF2a. Overexpression of miR-200s led to cell cycle arrest in the G1 phase and induced apoptotic responses during embryo development, thereby inhibiting somatic growth of zebrafish embryos. Intriguingly, GH induced expression of both p53 and miR-200s, and miR-200s is a potential p53 transcriptional target, thus forming a negative feedback loop. Significantly, the up-regulation of miR-200s associated with GH activation is abolished in embryos with p53 mutation. By integrating these studies, we conclude that p53/miR-200 and GH/IGF signaling pathway form a negative regulatory loop to control embryo size, that provide critical insights into the long-standing puzzle of how body growth is determined during early development of teleosts. PMID:26507500

  2. Multiple high voltage output DC-to-DC power converter

    NASA Technical Reports Server (NTRS)

    Cronin, Donald L. (Inventor); Farber, Bertrand F. (Inventor); Gehm, Hartmut K. (Inventor); Goldin, Daniel S. (Inventor)

    1977-01-01

    Disclosed is a multiple output DC-to-DC converter. The DC input power is filtered and passed through a chopper preregulator. The chopper output is then passed through a current source inverter controlled by a squarewave generator. The resultant AC is passed through the primary winding of a transformer, with high voltages induced in a plurality of secondary windings. The high voltage secondary outputs are each solid-state rectified for passage to individual output loads. Multiple feedback loops control the operation of the chopper preregulator, one being responsive to the current through the primary winding and another responsive to the DC voltage level at a selected output.

  3. Short-loop negative and positive feedback on ecdysone secretion by prothoracic gland in the tobacco hornworm, Manduca sexta.

    PubMed

    Sakurai, S; Williams, C M

    1989-08-01

    Ecdysteroid production by the prothoracic glands of the tobacco hornworm, Manduca sexta was found to be under feedback control by the ecdysteroids in hemolymph using both culture in vivo in diapausing pupae lacking the brain-corpora cardiaca-corpora allata complex and the prothoracic glands and culture in vitro. Prothoracic glands having relatively high activity in larvae, prepupae, or developing pupae were inhibited by ecdysone or 20-hydroxyecdysone. By contrast, prothoracic glands with low activity from feeding larvae, day 1 non-diapausing pupae and diapausing pupae were activated by both ecdysone and 20-hydroxyecdysone in vivo and in vitro. Dose-response studies on diapausing pupal glands showed that ecdysone was the most effective activator. These findings suggest that prothoracic glands are either stimulated or inhibited by ecdysone or 20-hydroxyecdysone, depending on both the secretory activity of the gland and the effective level of ecdysteroids in hemolymph. Thus, when the glands are first activated, the ecdysteroids that are secreted show a positive feedback on the glands to increase ecdysteroid output. Then the activated glands are turned off by the increasing 20-hydroxyecdysone titer in the hemolymph leading to the rapid decrease in ecdysteroid titer at the end of the molt period. PMID:2806870

  4. Global metabolic changes following loss of a feedback loop reveal dynamic steady states of the yeast metabolome.

    PubMed

    Lu, Peng; Rangan, Anupama; Chan, Sherwin Y; Appling, Dean R; Hoffman, David W; Marcotte, Edward M

    2007-01-01

    Metabolic enzymes control cellular metabolite concentrations dynamically in response to changing environmental and intracellular conditions. Such real-time feedback regulation suggests the global metabolome may sample distinct dynamic steady states, forming "basins of stability" in the energy landscape of possible metabolite concentrations and enzymatic activities. Using metabolite, protein and transcriptional profiling, we characterize three dynamic steady states of the yeast metabolome that form by perturbing synthesis of the universal methyl donor S-adenosylmethionine (AdoMet). Conversion between these states is driven by replacement of serine with glycine+formate in the media, loss of feedback inhibition control by the metabolic enzyme Met13, or both. The latter causes hyperaccumulation of methionine and AdoMet, and dramatic global compensatory changes in the metabolome, including differences in amino acid and sugar metabolism, and possibly in the global nitrogen balance, ultimately leading to a G1/S phase cell cycle delay. Global metabolic changes are not necessarily accompanied by global transcriptional changes, and metabolite-controlled post-transcriptional regulation of metabolic enzymes is clearly evident. PMID:17049899

  5. Closing a quantum feedback loop inside a cryostat: Autonomous state preparation and long-time memory of a superconducting qubit

    NASA Astrophysics Data System (ADS)

    Andersen, Christian Kraglund; Kerckhoff, Joseph; Lehnert, Konrad W.; Chapman, Benjamin J.; Mølmer, Klaus

    2016-01-01

    We propose to use a nonlinear resonator for projective readout, classical memory, and feedback for a superconducting qubit. Keeping the classical controller at cryogenic temperatures sidesteps many of the inefficiencies inherent in two-way communication between temperature stages in typical systems with room-temperature controllers, and avoids increasing the cryogenic heat load. This controller may find a broad range of uses in multiqubit systems, but here we analyze two specific demonstrative cases in single qubit control. In the first case, the nonlinear controller is used to initialize the qubit in a definite eigenstate. And in the second case, the qubit's state is read into the controller's classical memory and used to reinstate the measured state after the qubit has decayed. We analyze the properties of this system and we show simulations of the time evolution for the full system dynamics.

  6. Harvesting entropy and quantifying the transition from noise to chaos in a photon-counting feedback loop

    PubMed Central

    Hagerstrom, Aaron Morgan; Murphy, Thomas Edward; Roy, Rajarshi

    2015-01-01

    Many physical processes, including the intensity fluctuations of a chaotic laser, the detection of single photons, and the Brownian motion of a microscopic particle in a fluid are unpredictable, at least on long timescales. This unpredictability can be due to a variety of physical mechanisms, but it is quantified by an entropy rate. This rate, which describes how quickly a system produces new and random information, is fundamentally important in statistical mechanics and practically important for random number generation. We experimentally study entropy generation and the emergence of deterministic chaotic dynamics from discrete noise in a system that applies feedback to a weak optical signal at the single-photon level. We show that the dynamics transition from shot noise to chaos as the photon rate increases and that the entropy rate can reflect either the deterministic or noisy aspects of the system depending on the sampling rate and resolution. PMID:26175023

  7. Fast flux locked loop

    DOEpatents

    Ganther, Jr., Kenneth R.; Snapp, Lowell D.

    2002-09-10

    A flux locked loop for providing an electrical feedback signal, the flux locked loop employing radio-frequency components and technology to extend the flux modulation frequency and tracking loop bandwidth. The flux locked loop of the present invention has particularly useful application in read-out electronics for DC SQUID magnetic measurement systems, in which case the electrical signal output by the flux locked loop represents an unknown magnetic flux applied to the DC SQUID.

  8. MSK1 and MSK2 inhibit lipopolysaccharide-induced prostaglandin production via an interleukin-10 feedback loop.

    PubMed

    MacKenzie, Kirsty F; Van Den Bosch, Mirjam W M; Naqvi, Shaista; Elcombe, Suzanne E; McGuire, Victoria A; Reith, Alastair D; Blackshear, Perry J; Dean, Jonathan L E; Arthur, J Simon C

    2013-04-01

    Prostaglandin production is catalyzed by cyclooxygenase 2 (cox-2). We demonstrate here that MSK1 and MSK2 (MSK1/2) can exert control on the induction of cox-2 mRNA by Toll-like receptor (TLR) agonists. In the initial phase of cox-2 induction, MSK1/2 knockout macrophages confirmed a role for MSK in the positive regulation of transcription. However, at later time points both lipopolysaccharide (LPS)-induced prostaglandin and cox-2 protein levels were increased in MSK1/2 knockout. Further analysis found that while MSKs promoted cox-2 mRNA transcription, following longer LPS stimulation MSKs also promoted degradation of cox-2 mRNA. This was found to be the result of an interleukin 10 (IL-10) feedback mechanism, with endogenously produced IL-10 promoting cox-2 degradation. The ability of IL-10 to do this was dependent on the mRNA binding protein TTP through a p38/MK2-mediated mechanism. As MSKs regulate IL-10 production in response to LPS, MSK1/2 knockout results in reduced IL-10 secretion and therefore reduced feedback from IL-10 on cox-2 mRNA stability. Following LPS stimulation, this increased mRNA stability correlated to an elevated induction of both of cox-2 protein and prostaglandin secretion in MSK1/2 knockout macrophages relative to that in wild-type cells. This was not restricted to isolated macrophages, as a similar effect of MSK1/2 knockout was seen on plasma prostaglandin E2 (PGE2) levels following intraperitoneal injection of LPS. PMID:23382072

  9. A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans

    PubMed Central

    Mandinova, Anna; Kolev, Vihren; Neel, Victor; Hu, Bing; Stonely, Wesley; Lieb, Jocelyn; Wu, Xunwei; Colli, Claudia; Han, Rong; Pazin, Mike; Ostano, Paola; Dummer, Reinhard; Brissette, Janice L.; Dotto, G. Paolo

    2009-01-01

    Seborrheic keratoses (SKs) are common, benign epithelial tumors of the skin that do not, or very rarely, progress into malignancy, for reasons that are not understood. We investigated this by gene expression profiling of human SKs and cutaneous squamous cell carcinomas (SCCs) and found that several genes previously connected with keratinocyte tumor development were similarly modulated in SKs and SCCs, whereas the expression of others differed by only a few fold. In contrast, the tyrosine kinase receptor FGF receptor–3 (FGFR3) and the transcription factor forkhead box N1 (FOXN1) were highly expressed in SKs, and close to undetectable in SCCs. We also showed that increased FGFR3 activity was sufficient to induce FOXN1 expression, counteract the inhibitory effect of EGFR signaling on FOXN1 expression and differentiation, and induce differentiation in a FOXN1-dependent manner. Knockdown of FOXN1 expression in primary human keratinocytes cooperated with oncogenic RAS in the induction of SCC-like tumors, whereas increased FOXN1 expression triggered the SCC cells to shift to a benign SK-like tumor phenotype, which included increased FGFR3 expression. Thus, we have uncovered a positive regulatory loop between FGFR3 and FOXN1 that underlies a benign versus malignant skin tumor phenotype. PMID:19729838

  10. A positive feedback loop involving Erk5 and Akt turns on mesangial cell proliferation in response to PDGF.

    PubMed

    Bera, Amit; Das, Falguni; Ghosh-Choudhury, Nandini; Li, Xiaonan; Pal, Sanjay; Gorin, Yves; Kasinath, Balakuntalam S; Abboud, Hanna E; Ghosh Choudhury, Goutam

    2014-06-01

    Platelet-derived growth factor BB and its receptor (PDGFRβ) play a pivotal role in the development of renal glomerular mesangial cells. Their roles in increased mesangial cell proliferation during mesangioproliferative glomerulonephritis have long been noted, but the operating logic of signaling mechanisms regulating these changes remains poorly understood. We examined the role of a recently identified MAPK, Erk5, in this process. PDGF increased the activating phosphorylation of Erk5 and tyrosine phosphorylation of proteins in a time-dependent manner. A pharmacologic inhibitor of Erk5, XMD8-92, abrogated PDGF-induced DNA synthesis and mesangial cell proliferation. Similarly, expression of dominant negative Erk5 or siRNAs against Erk5 blocked PDGF-stimulated DNA synthesis and proliferation. Inhibition of Erk5 attenuated expression of cyclin D1 mRNA and protein, resulting in suppression of CDK4-mediated phosphorylation of the tumor suppressor protein pRb. Expression of cyclin D1 or CDK4 prevented the dominant negative Erk5- or siErk5-mediated inhibition of DNA synthesis and mesangial cell proliferation induced by PDGF. We have previously shown that phosphatidylinositol 3-kinase (PI3-kinase) contributes to PDGF-induced proliferation of mesangial cells. Inhibition of PI3-kinase blocked PDGF-induced phosphorylation of Erk5. Since PI3-kinase acts through Akt, we determined the role of Erk5 on Akt phosphorylation. XMD8-92, dominant negative Erk5, and siErk5 inhibited phosphorylation of Akt by PDGF. Interestingly, we found inhibition of PDGF-induced Erk5 phosphorylation by a pharmacological inhibitor of Akt kinase and kinase dead Akt in mesangial cells. Thus our data unfold the presence of a positive feedback microcircuit between Erk5 and Akt downstream of PI3-kinase nodal point for PDGF-induced mesangial cell proliferation. PMID:24740537

  11. A miR-221/222-mediated feedback loop maintains constitutive activation of NF-κB and STAT3 signaling in human colorectal cancers

    PubMed Central

    Liu, Sanhong; Sun, Xiaohua; Jiang, Yuhang; Liu, Zhanjie; Cao, Xinwei; Hou, Yingyong; Zhan, Yu; Tao, Yu; Wang, Lunshan; Xu, Chen; Chin, Eugene Y; Shi, Yufang; Siebenlist, Ulrich; Zhang, Xiaoren

    2016-01-01

    Background & Aims Constitutive activation of NF-κB and STAT3 pathways in human colorectal cancers links inflammation to CRC development and progression. However, the underlying mechanisms remain to be elucidated. Here we investigated the roles of miR-221 and miR-222 in regulating both NF-κB and STAT3 activities and colorectal tumorigenesis. Methods miR-221/222 mimics and their inhibitors/sponges were transiently or stably transfected into cells. Dual luciferase reporter assays were utilized to examine the activation of both NF-κB and STAT3 signaling, as well as the regulation of miR-221/222. Quantitative PCR and immunoblot analysis were employed to examine the mRNA and protein expression. MTT assay, flow cytometric analysis and xenotransplant of tumor cells were performed to investigate the CRC cell growth in vitro and in vivo. Results miR-221 and miR-222 positively regulate both NF-κB and STAT3 activities, which in return induce miR-221/222 expression, creating a positive feedback loop in human CRCs. miR-221/222 directly bind to the coding region of RelA, leading to increased RelA mRNA stability. In addition, miR-221/222 reduce ubiquitination of RelA and STAT3 proteins by directly targeting the 3′ UTR of PDLIM2, an E3 ligase for both RelA and STAT3. We demonstrate that disruption of the positive feedback loop suppresses human CRC cell growth in vitro and in vivo. The expression of miR-221/222 correlates with the expression of RelA, STAT3 and PDLIM2 in human CRC clinical samples. Conclusions Our findings define a novel miR-221/222 mediated mechanism underlying constitutive activation of NF-κB and STAT3 pathways in human CRCs and provide a promising therapeutic target for human CRCs. PMID:24931456

  12. Constant peak-power single-frequency linearly-polarized all-fiber laser for coherent detection based on closed-loop feedback technology

    NASA Astrophysics Data System (ADS)

    Ding, Yaqian; Zhang, Xiang; Li, Dong; Wang, Dapeng; Zhang, Renzhong; Song, Chengying; Che, Haozhao; Wang, Rui; Guo, Baoling; Chen, Guanghui

    2015-10-01

    In this paper, a practical single-frequency high-repetition linearly-polarized eye-safe all-fiber laser with constant peak power is demonstrated. It is based on master-oscillator power amplifier (MOPA) system. A distributed feedback laser diode simulating at 1550nm with narrow linewidth of 2.3 kHz is employed as the seed source. It is modulated to a pulse laser with high repetition of 20 kHz and peak power of 10mW by an acousto-optic modulator (AOM). The pulse width is tunable between 100ns to 400ns. Two-stage cascade amplifier is established, which consists of a pre-amplifier and a power-amplifier. Amplified spontaneous emission (ASE) and stimulated billion scattering are well suppressed by special management. The output peak power of 30W is obtained, which has nearly diffraction-limited beam quality. It operates in linewidth of 1.2MHz, polarization-extinction ratio (PER) of 25dB and signal-to-noise ratio (SNR) of more than 40dB. Gain of the whole amplifier achieves nearly 35dB. Furthermore, an embedded control system (ECS) based on the WinCE operating system (OS) and the chip of S3C2440 is proposed. This control system based on closed-loop feedback technology makes the peak power keeping constant even the pulse width tunable, which is convenient for the end user of the radar. This robust portable laser is remarkable and fulfills the desire of coherent detection excellently.

  13. miR-217 and CAGE form feedback loop and regulates the response to anti-cancer drugs through EGFR and HER2.

    PubMed

    Kim, Youngmi; Kim, Hyuna; Park, Deokbum; Han, Minho; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil

    2016-03-01

    MicroRNA array analysis revealed that miR-217 expression was decreased in anti-cancer drug-resistant Malme3MR cancer cells. CAGE, a cancer/testis antigen, was predicted as a target of miR-217. Luciferase activity and ChIP assays revealed a negative feedback relationship between CAGE and miR-217. miR-217 and CAGE oppositely regulated the response to anti-cancer drugs such as taxol, gefitinib and trastuzumab, an inhibitor of HER2. miR-217 negatively regulated the tumorigenic, metastatic, angiogenic, migration and invasion potential of cancer cells. The xenograft of Malme3MR cells showed an increased expression of pEGFRY845. CAGE and miR-217 inhibitor regulated the expression of pEGFRY845. CAGE showed interactions with EGFR and HER2 and regulated the in vivo sensitivity to trastuzumab. The down-regulation of EGFR or HER2 enhanced the sensitivity to anti-cancer drugs. CAGE showed direct regulation of HER2 and was necessary for the interaction between EGFR and HER2 in Malme3MR cells. miR-217 inhibitor induced interactions of CAGE with EGFR and HER2 in Malme3M cells. The inhibition of EGFR by CAGE-binding GTGKT peptide enhanced the sensitivity to gefitinib and trastuzumab and prevented interactions of EGFR with CAGE and HER2. Our results show that miR-217-CAGE feedback loop serves as a target for overcoming resistance to various anti-cancer drugs, including EGFR and HER2 inhibitors. PMID:26863629

  14. GIV/Girdin (Gα-interacting, Vesicle-associated Protein/Girdin) Creates a Positive Feedback Loop That Potentiates Outside-in Integrin Signaling in Cancer Cells.

    PubMed

    Leyme, Anthony; Marivin, Arthur; Garcia-Marcos, Mikel

    2016-04-01

    Activation of the tyrosine kinase focal adhesion kinase (FAK) upon cell stimulation by the extracellular matrix initiates integrin outside-in signaling. FAK is directly recruited to active integrins, which enhances its kinase activity and triggers downstream signaling like activation of PI3K. We recently described that Gα-interacting, vesicle-associated protein (GIV), a protein up-regulated in metastatic cancers, is also required for outside-in integrin signaling. More specifically, we found that GIV is a non-receptor guanine nucleotide exchange factor that activates trimeric G proteins in response to integrin stimulation to enhance PI3K signaling and tumor cell migration. In contrast, previous reports have established that GIV is involved in phosphotyrosine (Tyr(P))-based signaling in response to growth factor stimulation;i.e.GIV phosphorylation at Tyr-1764 and Tyr-1798 recruits and activates PI3K. Here we show that phosphorylation of GIV at Tyr-1764/Tyr-1798 is also required to enhance PI3K-Akt signaling and tumor cell migration in response to integrin stimulation, indicating that GIV functions in Tyr(P)-dependent integrin signaling. Unexpectedly, we found that activation of FAK, an upstream component of the integrin Tyr(P) signaling cascade, was diminished in GIV-depleted cells, suggesting that GIV is required to establish a positive feedback loop that enhances integrin-FAK signaling. Mechanistically, we demonstrate that this feedback activation of FAK depends on both guanine nucleotide exchange factor and Tyr(P) GIV signaling as well as on their convergence point, PI3K. Taken together, our results provide novel mechanistic insights into how GIV promotes proinvasive cancer cell behavior by working as a signal-amplifying platform at the crossroads of trimeric G protein and Tyr(P) signaling. PMID:26887938

  15. Evolution of Double Positive Autoregulatory Feedback Loops in CYCLOIDEA2 Clade Genes Is Associated with the Origin of Floral Zygomorphy[W

    PubMed Central

    Yang, Xia; Pang, Hong-Bo; Liu, Bo-Ling; Qiu, Zhi-Jing; Gao, Qiu; Wei, Lai; Dong, Yang; Wang, Yin-Zheng

    2012-01-01

    Members of the CYCLOIDEA2 (CYC2) clade of the TEOSINTE BRANCHED1, CYCLOIDEA, and PCF transcription factor genes are widely involved in controlling floral zygomorphy, a key innovation in angiosperm evolution, depending on their persistently asymmetric expression in the corresponding floral domains. However, it is unclear how this asymmetric expression is maintained throughout floral development. Selecting Primulina heterotricha as a model, we examined the expression and function of two CYC2 genes, CYC1C and CYC1D. We analyzed the role of their promoters in protein–DNA interactions and transcription activation using electrophoresis mobility shift assays, chromatin immunoprecipitation, and transient gene expression assays. We find that CYC1C and CYC1D positively autoregulate themselves and cross-regulate each other. Our results reveal a double positive autoregulatory feedback loop, evolved for a pair of CYC2 genes to maintain their expression in developing flowers. Further comparative genome analyses, together with the available expression and function data of CYC2 genes in the core eudicots, suggest that this mechanism might have led to the independent origins of floral zygomorphy, which are associated with plant–insect coevolution and the adaptive radiation of angiosperms. PMID:22649271

  16. Fbw7 repression by hes5 creates a feedback loop that modulates Notch-mediated intestinal and neural stem cell fate decisions.

    PubMed

    Sancho, Rocio; Blake, Sophia M; Tendeng, Christian; Clurman, Bruce E; Lewis, Julian; Behrens, Axel

    2013-01-01

    FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins. The Fbw7 locus comprises three different isoforms, each with its own promoter and each suspected to have a distinct set of substrates. Most FBW7 targets have important functions in developmental processes and oncogenesis, including Notch proteins, which are functionally important substrates of SCF(Fbw7). Notch signalling controls a plethora of cell differentiation decisions in a wide range of species. A prominent role of this signalling pathway is that of mediating lateral inhibition, a process where exchange of signals that repress Notch ligand production amplifies initial differences in Notch activation levels between neighbouring cells, resulting in unequal cell differentiation decisions. Here we show that the downstream Notch signalling effector HES5 directly represses transcription of the E3 ligase Fbw7β, thereby directly bearing on the process of lateral inhibition. Fbw7(Δ/+) heterozygous mice showed haploinsufficiency for Notch degradation causing impaired intestinal progenitor cell and neural stem cell differentiation. Notably, concomitant inactivation of Hes5 rescued both phenotypes and restored normal stem cell differentiation potential. In silico modelling suggests that the NICD/HES5/FBW7β positive feedback loop underlies Fbw7 haploinsufficiency. Thus repression of Fbw7β transcription by Notch signalling is an essential mechanism that is coupled to and required for the correct specification of cell fates induced by lateral inhibition. PMID:23776410

  17. HD-ZIP III Activity Is Modulated by Competitive Inhibitors via a Feedback Loop in Arabidopsis Shoot Apical Meristem Development[W

    PubMed Central

    Kim, Youn-Sung; Kim, Sang-Gyu; Lee, Minsun; Lee, Ilha; Park, Hye-Young; Seo, Pil Joon; Jung, Jae-Hoon; Kwon, Eun-Jung; Suh, Se Won; Paek, Kyung-Hee; Park, Chung-Mo

    2008-01-01

    Shoot apical meristem (SAM) development is coordinately regulated by two interdependent signaling events: one maintaining stem cell identity and the other governing the initiation of lateral organs from the flanks of the SAM. The signaling networks involved in this process are interconnected and are regulated by multiple molecular mechanisms. Class III homeodomain-leucine zipper (HD-ZIP III) proteins are the most extensively studied transcription factors involved in this regulation. However, how different signals are integrated to maintain stem cell identity and to pattern lateral organ polarity remains unclear. Here, we demonstrated that a small ZIP protein, ZPR3, and its functionally redundant homolog, ZPR4, negatively regulate the HD-ZIP III activity in SAM development. ZPR3 directly interacts with PHABULOSA (PHB) and other HD-ZIP III proteins via the ZIP motifs and forms nonfunctional heterodimers. Accordingly, a double mutant, zpr3-2 zpr4-2, exhibits an altered SAM activity with abnormal stem cell maintenance. However, the mutant displays normal patterning of leaf polarity. In addition, we show that PHB positively regulates ZPR3 expression. We therefore propose that HD-ZIP III activity in regulating SAM development is modulated by, among other things, a feedback loop involving the competitive inhibitors ZPR3 and ZPR4. PMID:18408069

  18. Diabetes-Induced Oxidative Stress in Endothelial Progenitor Cells May Be Sustained by a Positive Feedback Loop Involving High Mobility Group Box-1

    PubMed Central

    Wu, Han; Li, Ran; Wei, Zhong-Hai; Zhang, Xin-Lin; Chen, Jian-Zhou; Dai, Qing; Xie, Jun; Xu, Biao

    2016-01-01

    Oxidative stress is considered to be a critical factor in diabetes-induced endothelial progenitor cell (EPC) dysfunction, although the underlying mechanisms are not fully understood. In this study, we investigated the role of high mobility group box-1 (HMGB-1) in diabetes-induced oxidative stress. HMGB-1 was upregulated in both serum and bone marrow-derived monocytes from diabetic mice compared with control mice. In vitro, advanced glycation end productions (AGEs) induced, expression of HMGB-1 in EPCs and in cell culture supernatants in a dose-dependent manner. However, inhibition of oxidative stress with N-acetylcysteine (NAC) partially inhibited the induction of HMGB-1 induced by AGEs. Furthermore, p66shc expression in EPCs induced by AGEs was abrogated by incubation with glycyrrhizin (Gly), while increased superoxide dismutase (SOD) activity in cell culture supernatants was observed in the Gly treated group. Thus, HMGB-1 may play an important role in diabetes-induced oxidative stress in EPCs via a positive feedback loop involving the AGE/reactive oxygen species/HMGB-1 pathway. PMID:26798412

  19. Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells

    PubMed Central

    Li, Hongzhong; Yang, Bing; Huang, Jing; Lin, Yong; Xiang, Tingxiu; Wan, Jingyuan; Li, Hongyuan; Chouaib, Salem; Ren, Guosheng

    2015-01-01

    Tumor-associated macrophages (TAMs) play an important role in cancer cell survival, however, the mechanism of which remains elusive. In this study, we found that COX-2 was abundantly expressed in breast TAMs, which was correlated to poor prognosis in breast cancer patients. Ectopic over-expression of COX-2 in TAMs enhanced breast cancer cell survival both in vitro and in vivo. COX-2 in TAMs was determined to be essential for the induction and maintenance of M2-phenotype macrophage polarity. COX-2+ TAMs promoted breast cancer cell proliferation and survival by increasing Bcl-2 and P-gp and decreasing Bax in cancer cells. Furthermore, COX-2 in TAMs induced the expression of COX-2 in breast cancer cells, which in turn promoted M2 macrophage polarization. Inhibiting PI3K/Akt pathway in cancer cells suppressed COX-2+ TAMs-induced cancer cell survival. These findings suggest that COX-2, functions as a key cancer promoting factor by triggering a positive-feedback loop between macrophages and cancer cells, which could be exploited for breast cancer prevention and therapy. PMID:26359357

  20. PKM2 promotes glucose metabolism and cell growth in gliomas through a mechanism involving a let-7a/c-Myc/hnRNPA1 feedback loop

    PubMed Central

    Wang, Jiajia; Zhang, Junxia; Qian, Jin; Li, Ri; Tao, Tao; Wei, Wenjin; Hu, Qi; Liu, Ning; You, Yongping

    2015-01-01

    Tumor cells metabolize more glucose to lactate in aerobic or hypoxic conditions than non-tumor cells. Pyruvate kinase isoenzyme type M2 (PKM2) is crucial for tumor cell aerobic glycolysis. We established a role for let-7a/c-Myc/hnRNPA1/PKM2 signaling in glioma cell glucose metabolism. PKM2 depletion via siRNA inhibits cell proliferation and aerobic glycolysis in glioma cells. C-Myc promotes up-regulation of hnRNPA1 expression, hnRNPA1 binding to PKM pre-mRNA, and the subsequent formation of PKM2. This pathway is downregulated by the microRNA let-7a, which functionally targets c-Myc, whereas hnRNPA1 blocks the biogenesis of let-7a to counteract its ability to downregulate the c-Myc/hnRNPA1/PKM2 signaling pathway. The down-regulation of c-Myc/hnRNPA1/PKM2 by let-7a is verified using a glioma xenograft model. These results suggest that let-7a, c-Myc and hnRNPA1 from a feedback loop, thereby regulating PKM2 expression to modulate glucose metabolism of glioma cells. These findings elucidate a new pathway mediating aerobic glycolysis in gliomas and provide an attractive potential target for therapeutic intervention. PMID:25948776

  1. Delay-induced oscillations in Wilson and Cowan's model: an analysis of the subthalamo-pallidal feedback loop in healthy and parkinsonian subjects.

    PubMed

    Pasillas-Lépine, William

    2013-06-01

    The model proposed by Wilson and Cowan (1972) describes the dynamics of two interacting subpopulations of excitatory and inhibitory neurons. It has been used to model neural structures like the olfactory bulb, whisker barrels, and the subthalamo-pallidal system. It is well-known that this system can exhibit an oscillatory behavior that is amplified by the presence of delays. In the absence of delays, the conditions for stability are well-known. The aim of our paper is to clarify these conditions when delays are included in the model. The first ingredient of our methods is a new necessary and sufficient condition for the existence of multiple equilibria. This condition is related to those for local asymptotic stability. In addition, a sufficient condition for global stability is also proposed. The second and main ingredient is a stability analysis of the system in the frequency-domain, based on the Nyquist criterion, that takes the four independent delays into account. The methods proposed in this paper can be applied to analyse the stability of the subthalamo-pallidal feedback loop, a deep brain structure involved in Parkinson's disease. Our stability conditions are easy to compute and characterize sharply the system's parameters for which spontaneous oscillations appear. PMID:23400597

  2. Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells.

    PubMed

    Li, Hongzhong; Yang, Bing; Huang, Jing; Lin, Yong; Xiang, Tingxiu; Wan, Jingyuan; Li, Hongyuan; Chouaib, Salem; Ren, Guosheng

    2015-10-01

    Tumor-associated macrophages (TAMs) play an important role in cancer cell survival, however, the mechanism of which remains elusive. In this study, we found that COX-2 was abundantly expressed in breast TAMs, which was correlated to poor prognosis in breast cancer patients. Ectopic over-expression of COX-2 in TAMs enhanced breast cancer cell survival both in vitro and in vivo. COX-2 in TAMs was determined to be essential for the induction and maintenance of M2-phenotype macrophage polarity. COX-2(+) TAMs promoted breast cancer cell proliferation and survival by increasing Bcl-2 and P-gp and decreasing Bax in cancer cells. Furthermore, COX-2 in TAMs induced the expression of COX-2 in breast cancer cells, which in turn promoted M2 macrophage polarization. Inhibiting PI3K/Akt pathway in cancer cells suppressed COX-2(+) TAMs-induced cancer cell survival. These findings suggest that COX-2, functions as a key cancer promoting factor by triggering a positive-feedback loop between macrophages and cancer cells, which could be exploited for breast cancer prevention and therapy. PMID:26359357

  3. KIF4A and PP2A–B56 form a spatially restricted feedback loop opposing Aurora B at the anaphase central spindle

    PubMed Central

    Bastos, Ricardo Nunes; Cundell, Michael J.

    2014-01-01

    The mitotic kinase Aurora B is concentrated at the anaphase central spindle by the kinesin MKlp2 during mitotic exit and cytokinesis. This pool of Aurora B phosphorylates substrates including the kinesin KIF4A to regulate central spindle length. In this paper, we identify a counteracting system in which PP2A–B56γ and -ε, but not PP2A–B56α, -β, and -δ, are maintained at the central spindle by KIF4A. Biochemical assays show that PP2A–B56γ can dephosphorylate the T799 Aurora B site on KIF4A and thereby counteract the Aurora B– and microtubule-stimulated ATPase activity of KIF4A. In agreement with these observations, combined silencing of PP2A–B56γ and -ε resulted in increased phosphorylation of KIF4A T799 and decreased central spindle growth in anaphase B. Furthermore, reduced turnover of regulatory phosphorylation on another Aurora B substrate MKlp1 was observed, suggesting that PP2A–B56γ and -ε play a general role opposing Aurora B at the central spindle. KIF4A and PP2A–B56γ and -ε therefore create a spatially restricted negative feedback loop counteracting Aurora B in anaphase. PMID:25512391

  4. MiR218 Modulates Wnt Signaling in Mouse Cardiac Stem Cells by Promoting Proliferation and Inhibiting Differentiation through a Positive Feedback Loop

    PubMed Central

    Wang, Yongshun; Liu, Jingjin; Cui, Jinjin; Sun, Meng; Du, Wenjuan; Chen, Tao; Ming, Xing; Zhang, Lulu; Tian, Jiangtian; Li, Ji; Yin, Li; Liu, Fang; Pu, Zhongyue; Lv, Bo; Hou, Jingbo; Yu, Bo

    2016-01-01

    MiRNA expression was determined in both proliferating and differentiated cardiac stem cells (CSCs) through a comprehensive miRNA microarray analysis. We selected miR218 for functional follow-up studies to examine its significance in CSCs. First, we observed that the expression of miR218 was altered in CSCs during differentiation into cardiomyocytes, and transfection of an miR218 mimic or miR218 inhibitor affected the myocardial differentiation of CSCs. Furthermore, we observed that a negative regulator of Wnt signaling, sFRP2, was a direct target of miR218, and the protein levels of sFRP2 were increased in cells transfected with the synthetic miR218 inhibitor. In contrast, transfection with the miR218 mimic decreased the expression of sFRP2 and potentiated Wnt signaling. The subsequent down-regulation of sFRP2 by shRNA potentiated Wnt signaling, contributing to a gene expression program that is important for CSC proliferation and cardiac differentiation. Specifically, canonical Wnt signaling induced miR218 transcription. Thus, miR218 and Wnt signaling were coupled through a feed-forward positive feedback loop, forming a biological regulatory circuit. Together, these results provide the first evidence that miR218 plays an important role in CSC proliferation and differentiation through the canonical Wnt signaling pathway. PMID:26860887

  5. Angiomodulin is required for cardiogenesis of embryonic stem cells and is maintained by a feedback loop network of p63 and Activin-A.

    PubMed

    Wolchinsky, Zohar; Shivtiel, Shoham; Kouwenhoven, Evelyn Nathalie; Putin, Daria; Sprecher, Eli; Zhou, Huiqing; Rouleau, Matthieu; Aberdam, Daniel

    2014-01-01

    The transcription factor p63, member of the p53 gene family, encodes for two main isoforms, TAp63 and ΔNp63 with distinct functions on epithelial homeostasis and cancer. Recently, we discovered that TAp63 is essential for in vitro cardiogenesis and heart development in vivo. TAp63 is expressed by embryonic endoderm and acts on cardiac progenitors by a cell-non-autonomous manner. In the present study, we search for cardiogenic secreted factors that could be regulated by TAp63 and, by ChIP-seq analysis, identified Angiomodulin (AGM), also named IGFBP7 or IGFBP-rP1. We demonstrate that AGM is necessary for cardiac commitment of embryonic stem cells (ESCs) and its regulation depends on TAp63 isoform. TAp63 directly activates both AGM and Activin-A during ESC cardiogenesis while these secreted factors modulate TAp63 gene expression by a feedback loop mechanism. The molecular circuitry controlled by TAp63 on AGM/Activin-A signaling pathway and thus on cardiogenesis emphasizes the importance of p63 during early cardiac development. PMID:24145187

  6. Ontogeny of specific prolactin binding sites in the rat choroid plexus and their temporal relation to the prolactin short-loop feedback system

    SciTech Connect

    Silverman, .F.

    1985-01-01

    The development of prolactin receptors in the choroid plexus of the rat was examined using the in vivo autoradiographic approach employing the principle of competitive binding. Animals aged 0, 10, 14, and 18 days postnatal were perfusion fixed following hormone injection and prepared for light microscopic autoradiography. The choroid plexus first demonstrated specific binding of prolactin at 14 days postnatal. The lactogen specificity of these binding sites was further defined by the ability of I/sup 125/-prolactin to be displaced by unlabelled human growth hormone, which is lactogenic in rats, and not by unlabelled insulin, which is structurally dissimilar to prolactin. Morphometric analysis was performed on electron micrographs of choroid plexus from 10 and 14 day postnatal rats. The volume densities of constituents known to be involved in the synthesis and/or function of polypeptide hormone receptors were measured and differences tested for statistical significance. A semi-quantitative histo-fluorescence technique was used to evaluate the ability of prolactin to stimulate secretion of its inhibiting factor, dopamine, in 10 day postnatal rats. The present findings indicate that the ontogenesis of specific prolactin binding sites is not temporally connected with the establishment of the prolactin short-loop feedback system since activation of the system occurs prior to the establishment of specific prolactin binding at choroid plexus.

  7. Positive regulation of the Egr-1/osteopontin positive feedback loop in rat vascular smooth muscle cells by TGF-{beta}, ERK, JNK, and p38 MAPK signaling

    SciTech Connect

    Yu, Hong-Wei; Liu, Qi-Feng; Liu, Gui-Nan

    2010-05-28

    Previous studies identified a positive feedback loop in rat vascular smooth muscle cells (VSMCs) in which early growth response factor-1 (Egr-1) binds to the osteopontin (OPN) promoter and upregulates OPN expression, and OPN upregulates Egr-1 expression via the extracellular signal-regulated protein kinase (ERK) signaling pathway. The current study examined whether transforming growth factor-{beta} (TGF-{beta}) activity contributes to Egr-1 binding to the OPN promoter, and whether other signaling pathways act downstream of OPN to regulate Egr-1 expression. ChIP assays using an anti-Egr-1 antibody showed that amplification of the OPN promoter sequence decreased in TGF-{beta} DNA enzyme-transfected VSMCs relative to control VSMCs. Treatment of VSMCs with PD98059 (ERK inhibitor), SP600125 (JNK inhibitor), or SB203580 (p38 MAPK inhibitor) significantly inhibited OPN-induced Egr-1 expression, and PD98059 treatment was associated with the most significant decrease in Egr-1 expression. OPN-stimulated VSMC cell migration was inhibited by SP600125 or SB203580, but not by PD98059. Furthermore, MTT assays showed that OPN-mediated cell proliferation was inhibited by PD98059, but not by SP600125 or SB203580. Taken together, the results of the current study show that Egr-1 binding to the OPN promoter is positively regulated by TGF-{beta}, and that the p38 MAPK, JNK, and ERK pathways are involved in OPN-mediated Egr-1 upregulation.

  8. Regulation loops for the ring magnet power supplies in the SSC accelerator complex

    SciTech Connect

    Tacconi, E.; Christiansen, C.

    1993-05-01

    The SSC complex consists of five cascaded accelerators: The linear accelerator (linac) and four synchrotrons: The low energy booster (LEB), the medium energy booster (MEB), the high energy booster (HEB), and the collider. Twelve- or 24-pulse phase-controlled SCR power supplies are used to energize the ring magnets. Each power supply has a voltage loop designed to regulate the voltage applied to the magnets. The voltage regulation loops for these synchrotrons and the current regulation for the LEB are analyzed in this work. The digital voltage regulator is fiber-optic isolated from the power converter. It has a closed-loop bandwidth of 150 Hz with band rejections for 60-Hz and 120-Hz perturbations. The LEB has a very precise current regulation system composed of a feedforward compensator, a fast feedback regulator, and a slow synchronous regulator. The current regulation design is corroborated by computer simulations.

  9. A theoretical model of slow wave regulation using voltage-dependent synthesis of inositol 1,4,5-trisphosphate.

    PubMed Central

    Imtiaz, Mohammad S; Smith, David W; van Helden, Dirk F

    2002-01-01

    A qualitative mathematical model is presented that examines membrane potential feedback on synthesis of inositol 1,4,5-trisphosphate (IP(3)), and its role in generation and modulation of slow waves. Previous experimental studies indicate that slow waves show voltage dependence, and this is likely to result through membrane potential modulation of IP(3). It is proposed that the observed response of the tissue to current pulse, pulse train, and maintained current injection can be explained by changes in IP(3), modulated through a voltage-IP(3) feedback loop. Differences underlying the tissue responses to current injections of opposite polarities are shown to be due to the sequence of events following such currents. Results from this model are consistent with experimental findings and provide further understanding of these experimental observations. Specifically, we find that membrane potential can induce, abolish, and modulate slow wave frequency by altering the excitability of the tissue through the voltage-IP(3) feedback loop. PMID:12324409

  10. Adaptor protein CRK induces epithelial–mesenchymal transition and metastasis of bladder cancer cells through HGF/c-Met feedback loop

    PubMed Central

    Matsumoto, Ryuji; Tsuda, Masumi; Wang, Lei; Maishi, Nako; Abe, Takashige; Kimura, Taichi; Tanino, Mishie; Nishihara, Hiroshi; Hida, Kyoko; Ohba, Yusuke; Shinohara, Nobuo; Nonomura, Katsuya; Tanaka, Shinya

    2015-01-01

    We have previously reported that an adaptor protein CRK, including CRK-I and CRK-II, plays essential roles in the malignant potential of various aggressive human cancers, suggesting the validity of targeting CRK in molecular targeted therapy of a wide range of cancers. Nevertheless, the role of CRK in human bladder cancer with marked invasion, characterized by distant metastasis and poor prognosis, remains obscure. In the present study, immunohistochemistry indicated a striking enhancement of CRK-I/-II, but not CRK-like, in human bladder cancer tissues compared to normal urothelium. We established CRK-knockdown bladder cancer cells using 5637 and UM-UC-3, which showed a significant decline in cell migration, invasion, and proliferation. It is noteworthy that an elimination of CRK conferred suppressed phosphorylation of c-Met and the downstream scaffold protein Gab1 in a hepatocyte growth factor-dependent and -independent manner. In epithelial–mesenchymal transition-related molecules, E-cadherin was upregulated by CRK elimination, whereas N-cadherin, vimentin, and Zeb1 were downregulated. A similar effect was observed following treatment with c-Met inhibitor SU11274. Depletion of CRK significantly decreased cell proliferation of 5637 and UM-UC-3, consistent with reduced activity of ERK. An orthotopic xenograft model with bioluminescent imaging revealed that CRK knockdown significantly attenuated not only tumor volume but also the number of circulating tumor cells, resulted in a complete abrogation of metastasis. Taken together, this evidence uncovered essential roles of CRK in invasive bladder cancer through the hepatocyte growth factor/c-Met/CRK feedback loop for epithelial–mesenchymal transition induction. Thus, CRK might be a potent molecular target in bladder cancer, particularly for preventing metastasis, leading to the resolution of clinically longstanding critical issues. PMID:25816892

  11. CaCDPK15 positively regulates pepper responses to Ralstonia solanacearum inoculation and forms a positive-feedback loop with CaWRKY40 to amplify defense signaling.

    PubMed

    Shen, Lei; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Cheng, Wei; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Mou, Shaoliang; Liu, Zhiqin; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-01-01

    CaWRKY40 is a positive regulator of pepper (Capsicum annum) response to Ralstonia solanacearum inoculation (RSI), but the underlying mechanism remains largely unknown. Here, we functionally characterize CaCDPK15 in the defense signaling mediated by CaWRKY40. Pathogen-responsive TGA, W, and ERE boxes were identified in the CaCDPK15 promoter (pCaCDPK15), and pCaCDPK15-driven GUS expression was significantly enhanced in response to RSI and exogenously applied salicylic acid, methyl jasmonate, abscisic acid, and ethephon. Virus-induced gene silencing (VIGS) of CaCDPK15 significantly increased the susceptibility of pepper to RSI and downregulated the immunity-associated markers CaNPR1, CaPR1, and CaDEF1. By contrast, transient CaCDPK15 overexpression significantly activated hypersensitive response associated cell death, upregulated the immunity-associated marker genes, upregulated CaWRKY40 expression, and enriched CaWRKY40 at the promoters of its targets genes. Although CaCDPK15 failed to interact with CaWRKY40, the direct binding of CaWRKY40 to pCaCDPK15 was detected by chromatin immunoprecipitation, which was significantly potentiated by RSI in pepper plants. These combined results suggest that RSI in pepper induces CaCDPK15 and indirectly activates downstream CaWRKY40, which in turn potentiates CaCDPK15 expression. This positive-feedback loop would amplify defense signaling against RSI and efficiently activate strong plant immunity. PMID:26928570

  12. The cotton MYB108 forms a positive feedback regulation loop with CML11 and participates in the defense response against Verticillium dahliae infection.

    PubMed

    Cheng, Huan-Qing; Han, Li-Bo; Yang, Chun-Lin; Wu, Xiao-Min; Zhong, Nai-Qin; Wu, Jia-He; Wang, Fu-Xin; Wang, Hai-Yun; Xia, Gui-Xian

    2016-04-01

    Accumulating evidence indicates that plant MYB transcription factors participate in defense against pathogen attack, but their regulatory targets and related signaling processes remain largely unknown. Here, we identified a defense-related MYB gene (GhMYB108) from upland cotton (Gossypium hirsutum) and characterized its functional mechanism. Expression of GhMYB108 in cotton plants was induced by Verticillium dahliae infection and responded to the application of defense signaling molecules, including salicylic acid, jasmonic acid, and ethylene. Knockdown of GhMYB108 expression led to increased susceptibility of cotton plants to V. dahliae, while ecotopic overexpression of GhMYB108 in Arabidopsis thaliana conferred enhanced tolerance to the pathogen. Further analysis demonstrated that GhMYB108 interacted with the calmodulin-like protein GhCML11, and the two proteins form a positive feedback loop to enhance the transcription of GhCML11 in a calcium-dependent manner. Verticillium dahliae infection stimulated Ca(2+) influx into the cytosol in cotton root cells, but this response was disrupted in both GhCML11-silenced plants and GhMYB108-silenced plants in which expression of several calcium signaling-related genes was down-regulated. Taken together, these results indicate that GhMYB108 acts as a positive regulator in defense against V. dahliae infection by interacting with GhCML11. Furthermore, the data also revealed the important roles and synergetic regulation of MYB transcription factor, Ca(2+), and calmodulin in plant immune responses. PMID:26873979

  13. Formononetin promotes proliferation that involves a feedback loop of microRNA-375 and estrogen receptor alpha in estrogen receptor-positive cells.

    PubMed

    Chen, Jian; Zhang, Xing; Wang, Yong; Ye, Yu; Huang, Zhaoquan

    2016-03-01

    Formononetin is an O-methylated isoflavone that is isolated from the root of Astragalus membranaceus, and it has antitumorigenic effects. Our previous studies found that formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells. To further investigate the potential effect of formononetin in promoting cell proliferation in estrogen receptor (ER)-positive cells, we used in vivo and in vitro studies to elucidate the possible mechanism. ERα-positive cells (HUVEC, MCF-7) were treated with formononetin. The CCK8 assay, Hoechst 33258, and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ERα, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. ERα, p-Akt, and Bcl-2 expression was determined using Western blot. Compared with the control, low formononetin concentrations (2-6 μM) stimulated ERα-positive cell proliferation (HUVEC, MCF-7). The more sensitive HUVEC cells were used to study the relevant signaling pathway. After treatment with formononetin, ERα, miR-375, p-Akt, and Bcl-2 expression was significantly upregulated. The proliferative effect of formononetin was also blocked by a miR-375 inhibitor or raloxifene pretreatment. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with formononetin increased significantly, but the weight dramatically decreased with raloxifene or miR-375 inhibitor pretreatment before formononetin. This study demonstrated that formononetin promoted ERα-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ERα feedback loop. © 2015 Wiley Periodicals, Inc. PMID:25663261

  14. Downregulation of COMMD1 by miR-205 promotes a positive feedback loop for amplifying inflammatory- and stemness-associated properties of cancer cells.

    PubMed

    Yeh, D-W; Chen, Y-S; Lai, C-Y; Liu, Y-L; Lu, C-H; Lo, J-F; Chen, L; Hsu, L-C; Luo, Y; Xiang, R; Chuang, T-H

    2016-05-01

    Sustained activation of nuclear factor-κB (NF-κB) in cancer cells has been shown to promote inflammation, expansion of cancer stem cell (CSC) population, and tumor development. In contrast, recent studies reveal that CSCs exhibit increased inflammation due to constitutive NF-κB activation; however, the underlying molecular mechanism remains unclear. In the present study, the analysis of microarray data revealed upregulation of NF-κB-regulated pro-inflammatory genes and downregulation of copper metabolism MURR1 domain-containing 1 (COMMD1) during the enrichment for stemness in SAS head and neck squamous-cell carcinoma (HNSCC) cells. The 3'-UTR of COMMD1 mRNA contains microRNA (miR)-205 target site. Parallel studies with HNSCC and NSCLC cells indicated that miR-205 is upregulated upon NF-κB activation and suppresses COMMD1 expression in stemness-enriched cancer cells. COMMD1 negatively regulates the inflammatory responses induced by TLR agonists, IL-1β, and TNF-α by targeting RelA for degradation. The shRNA-mediated downregulation of COMMD1 in cancer cells enhanced inflammatory response, generating favorable conditions for macrophage recruitment. In addition, genes associated with stemness were also upregulated in these cells, which exhibited increased potential for anchorage-independent growth. Furthermore, COMMD1 downregulation promoted in vivo tumorigenesis and tumor growth, and tumors derived from COMMD1-knockdown cells displayed elevated level of NF-κB activation, increased expression of inflammatory- and stemness-associated genes, and contain expanded population of tumor-associated leukocytes and stemness-enriched cancer cells. These results suggest that COMMD1 downregulation by miR-205 promotes tumor development by modulating a positive feedback loop that amplifies inflammatory- and stemness-associated properties of cancer cells. PMID:26586569

  15. Interrupted E2F1-miR-34c-SCF negative feedback loop by hyper-methylation promotes colorectal cancer cell proliferation

    PubMed Central

    Yang, Shu; Wu, Bo; Sun, Haimei; Ji, Fengqing; Sun, Tingyi; Zhao, Yan; Zhou, Deshan

    2015-01-01

    Tumour suppressor miR-34c deficiency resulted from hyper-methylation in its promoter is believed to be one of the main causes of colorectal cancer (CRC). Till date, miR-34c has been validated as a direct target of p53; but previous evidence suggested other transcription factor(s) must be involved in miR-34c transcription. In the present study, we in the first place identified a core promoter region (−1118 to −883 bp) of pre-miR-34c which was embedded within a hyper-methylated CpG island. Secondly, E2F1 promoted miR-34c transcription by physical interaction with the miR-34c promoter at site −897 to −889 bp. The transcriptional activating effect of E2F1 on miR-34c was in a p53 independent manner but profoundly promoted in the presence of p53 with exposure to 5-aza-2′-deoxycytidine (DAC). Thirdly, stem cell factor (SCF), a miR-34c target, was specifically reduced upon an introduction of E2F1 which lead to suppression of CRC cell proliferation. The E2F1-suppressed cell proliferation was partially abrogated by additional miR-34c inhibitor, indicating that the anti-proliferation effect of E2F1 was probably through activating miR-34c-SCF axis. Finally, SCF/KIT signalling increased E2F1 production by reducing its proteosomal degradation dependent on PI3K/Akt-GSK3β pathway. In conclusion, our results suggested the existence of E2F1-miR-34c-SCF negative feedback loop which was interrupted by the hyper-methylation of miR-34c promoter in CRC cells and increased cell proliferation. PMID:26704889

  16. The cotton MYB108 forms a positive feedback regulation loop with CML11 and participates in the defense response against Verticillium dahliae infection

    PubMed Central

    Cheng, Huan-Qing; Han, Li-Bo; Yang, Chun-Lin; Wu, Xiao-Min; Zhong, Nai-Qin; Wu, Jia-He; Wang, Fu-Xin; Xia, Gui-Xian

    2016-01-01

    Accumulating evidence indicates that plant MYB transcription factors participate in defense against pathogen attack, but their regulatory targets and related signaling processes remain largely unknown. Here, we identified a defense-related MYB gene (GhMYB108) from upland cotton (Gossypium hirsutum) and characterized its functional mechanism. Expression of GhMYB108 in cotton plants was induced by Verticillium dahliae infection and responded to the application of defense signaling molecules, including salicylic acid, jasmonic acid, and ethylene. Knockdown of GhMYB108 expression led to increased susceptibility of cotton plants to V. dahliae, while ecotopic overexpression of GhMYB108 in Arabidopsis thaliana conferred enhanced tolerance to the pathogen. Further analysis demonstrated that GhMYB108 interacted with the calmodulin-like protein GhCML11, and the two proteins form a positive feedback loop to enhance the transcription of GhCML11 in a calcium-dependent manner. Verticillium dahliae infection stimulated Ca2+ influx into the cytosol in cotton root cells, but this response was disrupted in both GhCML11-silenced plants and GhMYB108-silenced plants in which expression of several calcium signaling-related genes was down-regulated. Taken together, these results indicate that GhMYB108 acts as a positive regulator in defense against V. dahliae infection by interacting with GhCML11. Furthermore, the data also revealed the important roles and synergetic regulation of MYB transcription factor, Ca2+, and calmodulin in plant immune responses. PMID:26873979

  17. Demonstration and biological significance of a gastrin‐P21‐activated kinase 1 feedback loop in colorectal cancer cells

    PubMed Central

    Huynh, Nhi; Liu, Kevin H.; Yim, Mildred; Shulkes, Arthur; Baldwin, Graham S.; He, Hong

    2014-01-01

    Abstract Gastrins, including amidated gastrin17 and glycine‐extended gastrin17, are important growth factors in colorectal cancer (CRC). The p21‐activated kinase 1 (PAK1) plays key roles in cellular processes including proliferation, survival, and motility, and in cell transformation and tumor progression. PAK1 expression increases with the progression of CRC, and knockdown of PAK1 blocks CRC cell growth and metastasis both in vitro and in vivo. The aim of this study was to determine the interaction between PAK1 and gastrins in CRC cells. PAK1 expression and activation were assayed by Western blots, and concentrations of gastrin mRNA and peptides by real‐time PCR and radioimmunoassay, respectively. Proliferation of CRC cells was measured by 3H‐thymidine incorporation, and vascular endothelial growth factor (VEGF) secretion was measured by ELISA. Gastrins activated PAK1 via PI3K‐dependent pathways. Activated PAK1 in turn mediated gastrin‐stimulated activation of β‐catenin and VEGF secretion in CRC cells, as knockdown of PAK1 blocked stimulation of these cellular processes by gastrins. Downregulation of gastrin reduced the expression and activity of PAK1, but in contrast there was a compensatory increase in gastrins either when PAK1 was downregulated, or after treatment with a PAK inhibitor. Our results indicate that PAK1 is required for the stimulation of CRC cells by gastrins, and suggest the existence of an inhibitory feedback loop by which PAK1 downregulates gastrin production in CRC cells. PMID:24963032

  18. CaCDPK15 positively regulates pepper responses to Ralstonia solanacearum inoculation and forms a positive-feedback loop with CaWRKY40 to amplify defense signaling

    PubMed Central

    Shen, Lei; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Cheng, Wei; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Mou, Shaoliang; Liu, Zhiqin; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-01-01

    CaWRKY40 is a positive regulator of pepper (Capsicum annum) response to Ralstonia solanacearum inoculation (RSI), but the underlying mechanism remains largely unknown. Here, we functionally characterize CaCDPK15 in the defense signaling mediated by CaWRKY40. Pathogen-responsive TGA, W, and ERE boxes were identified in the CaCDPK15 promoter (pCaCDPK15), and pCaCDPK15-driven GUS expression was significantly enhanced in response to RSI and exogenously applied salicylic acid, methyl jasmonate, abscisic acid, and ethephon. Virus-induced gene silencing (VIGS) of CaCDPK15 significantly increased the susceptibility of pepper to RSI and downregulated the immunity-associated markers CaNPR1, CaPR1, and CaDEF1. By contrast, transient CaCDPK15 overexpression significantly activated hypersensitive response associated cell death, upregulated the immunity-associated marker genes, upregulated CaWRKY40 expression, and enriched CaWRKY40 at the promoters of its targets genes. Although CaCDPK15 failed to interact with CaWRKY40, the direct binding of CaWRKY40 to pCaCDPK15 was detected by chromatin immunoprecipitation, which was significantly potentiated by RSI in pepper plants. These combined results suggest that RSI in pepper induces CaCDPK15 and indirectly activates downstream CaWRKY40, which in turn potentiates CaCDPK15 expression. This positive-feedback loop would amplify defense signaling against RSI and efficiently activate strong plant immunity. PMID:26928570

  19. Downregulation of COMMD1 by miR-205 promotes a positive feedback loop for amplifying inflammatory- and stemness-associated properties of cancer cells

    PubMed Central

    Yeh, D-W; Chen, Y-S; Lai, C-Y; Liu, Y-L; Lu, C-H; Lo, J-F; Chen, L; Hsu, L-C; Luo, Y; Xiang, R; Chuang, T-H

    2016-01-01

    Sustained activation of nuclear factor-κB (NF-κB) in cancer cells has been shown to promote inflammation, expansion of cancer stem cell (CSC) population, and tumor development. In contrast, recent studies reveal that CSCs exhibit increased inflammation due to constitutive NF-κB activation; however, the underlying molecular mechanism remains unclear. In the present study, the analysis of microarray data revealed upregulation of NF-κB-regulated pro-inflammatory genes and downregulation of copper metabolism MURR1 domain-containing 1 (COMMD1) during the enrichment for stemness in SAS head and neck squamous-cell carcinoma (HNSCC) cells. The 3′-UTR of COMMD1 mRNA contains microRNA (miR)-205 target site. Parallel studies with HNSCC and NSCLC cells indicated that miR-205 is upregulated upon NF-κB activation and suppresses COMMD1 expression in stemness-enriched cancer cells. COMMD1 negatively regulates the inflammatory responses induced by TLR agonists, IL-1β, and TNF-α by targeting RelA for degradation. The shRNA-mediated downregulation of COMMD1 in cancer cells enhanced inflammatory response, generating favorable conditions for macrophage recruitment. In addition, genes associated with stemness were also upregulated in these cells, which exhibited increased potential for anchorage-independent growth. Furthermore, COMMD1 downregulation promoted in vivo tumorigenesis and tumor growth, and tumors derived from COMMD1-knockdown cells displayed elevated level of NF-κB activation, increased expression of inflammatory- and stemness-associated genes, and contain expanded population of tumor-associated leukocytes and stemness-enriched cancer cells. These results suggest that COMMD1 downregulation by miR-205 promotes tumor development by modulating a positive feedback loop that amplifies inflammatory- and stemness-associated properties of cancer cells. PMID:26586569

  20. A detection of Milankovitch frequencies in tephra records of arc volcanism: Shedding light on a feedback loop between climate and volcanism. (Invited)

    NASA Astrophysics Data System (ADS)

    Kutterolf, S.; Jegen, M.; Schindlbeck, J. C.; Mitrovica, J. X.; Kwasnitschka, T.; Freundt, A.; Huybers, P. J.

    2013-12-01

    Although it is well understood that volcanism can impact global climate or tectonics can influence volcanism, it is less well appreciated that climate can influence volcanism. In this regard, both regional and global studies have provided compelling evidence that ice age loading processes modulate the frequency of volcanic eruption. However, a rigorous detection of Milankovitch periodicities in global volcanic output across the Pleistocene-Holocene ice age, which would firmly establish a connection between ice age climate and eruption frequency, has remained elusive. To this end, we report on a spectral analysis of a large number of well-preserved ash plume deposits recorded in marine sediments along the Pacific Ring of Fire, which accounts for about half of the global length of 44,000 km of active subduction. Eruptions at arc volcanoes tend to be highly explosive. We analyze the Pleistocene-to-Recent marine records of widespread tephras of sub-Plinian to Plinian, and occasionally co-ignimbrite, origin since they provide a well-preserved record of how eruption frequencies varied with depth (and, hence time). Our analysis yields a statistically significant detection of spectral peaks at the obliquity period. We propose that the variability in volcanic activity results from crustal stress changes associated with ice age mass redistribution. In particular, increased volcanism lags behind the highest rate of increasing eustatic sea level (decreasing global ice volume) by 4.0 × 3.6 kyr and correlates well with numerical predictions of stress changes at volcanically active sites. Our results strongly support the presence of a coupling between ice age climate, volcanism and the continental stress field. In future work we will incorporate longer tephra time series and more accurate age controls in order to improve - and widen - our detection of Milankovitch periodicities thus further elucidating the feedback loop between climate and volcanism as well as tectonics.

  1. Epithelial-mesenchymal transition and tumor suppression are controlled by a reciprocal feedback loop between ZEB1 and Grainyhead-like-2

    PubMed Central

    Cieply, Benjamin; Farris, Joshua; Denvir, James; Ford, Heide; Frisch, Steven M.

    2013-01-01

    Epithelial-mesenchymal transition (EMT) in carcinoma cells enhances malignant progression by promoting invasion and survival. EMT is induced by microenvironmental factors including TGF-β and Wnt agonists, and by the E-box-binding transcription factors Twist, Snail and ZEB. Grainyhead-like-2 (GRHL2), a member of the mammalian Grainyhead family of wound healing regulatory transcription factors, suppresses EMT and restores sensitivity to anoikis by repressing ZEB1 expression and inhibiting TGF-β signaling. In this study, we elucidate the functional relationship between GRHL2 and ZEB1 in EMT/MET and tumor biology. At least three homeodomain proteins, Six1, LBX1, and HoxA5, transactivated the ZEB1 promoter, in the case of Six1, through direct protein-promoter interaction. GRHL2 altered the Six1-DNA complex, inhibiting this transactivation. Correspondingly, GRHL2 expression prevented tumor initiation in xenograft assays, sensitized breast cancer cells to paclitaxel and suppressed the emergence of CD44highCD24low cells (defining the cancer stem cell phenotype in the cell type studied). GRHL2 was down-regulated in recurrent mouse tumors that had evolved to an oncogene-independent, EMT-like state, supporting a role for GRHL2 down-regulation in this phenotypic transition, modeling disease recurrence. The combination of TGF-β and Wnt activation repressed GRHL2 expression by direct interaction of ZEB1 with the GRHL2 promoter, inducing EMT. Together, our observations indicate that a reciprocal feedback loop between GRHL2 and ZEB1 controls epithelial vs. mesenchymal phenotypes and EMT-driven tumor progression. PMID:23943797

  2. Activation of ERK/IER3/PP2A-B56γ-positive feedback loop in lung adenocarcinoma by allelic deletion of B56γ gene.

    PubMed

    Ito, Tomoko; Ozaki, Satoru; Chanasong, Rachanee; Mizutani, Yuki; Oyama, Takeru; Sakurai, Hiroshi; Matsumoto, Isao; Takemura, Hirofumi; Kawahara, Ei

    2016-05-01

    In order to investigate the involvement of the IER3/PP2A-B56γ/ERK-positive feedback loop, which leads to sustained phosphorylation/activation of ERK in carcinogenesis, we immunohistochemically examined the expression of IER3 and phosphorylated ERK in lung tumor tissues. IER3 was overexpressed in all cases of adenocarcinomas examined, but was not overexpressed in squamous cell carcinomas. Phosphorylated ERK (pERK) was also overexpressed in almost all adenocarcinomas. EGFR and RAS, whose gene product is located upstream of ERK, were sequenced. Activating mutation of EGFR, which is a possible cause of overexpression of IER3 and pERK, was found only in 5 adenocarcinomas (42%). No mutation of RAS was found. We further examined the sequences of all exons of B56γ gene (PPP2R5C) and IER3, but no mutation was found. Using a single nucleotide insertion in intron 1 of PPP2R5C, which was found in the process of sequencing, allelic deletion of PPP2R5C was examined. Eight cases were informative (67%), and the deletion was found in 4 of them (50%). Three cases having deletion of PPP2R5C did not have EGFR mutation. Finally, PPP2R5C deletion or EGFR mutation that could be responsible for IER3/pERK overexpression was found in at least 8 cases (67% or more). This is the first report of a high incidence of deletion of PPP2R5C in human carcinomas. PMID:26986830

  3. Deregulation of NF-кB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy.

    PubMed

    Yousefzadeh, Nasibeh; Alipour, Mohammad Reza; Soufi, Farhad Ghadiri

    2015-03-01

    The current study was designed to explore whether microRNA-146a and its adapter proteins (tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1)) are involved in the pathogenesis of diabetes neuropathy. Twelve male Sprague Dawley rats were randomized into control and diabetic groups (n = 6). Diabetes was induced by a single-dose injection of nicotinamide (110 mg/kg; i.p.), 15 min before injection of streptozotocin (50 mg/kg; i.p.) in 12-h-fasted rats. Diabetic neuropathy was evaluated by hot plate and tail emersion tests, 2 months after the injection of streptozotocin. The gene expression level of microRNA-146a (miR-146a), IRAK1, TRAF6, and nuclear factor kappa B (NF-κB) was measured in the sciatic nerve of rats using the real time-PCR method. Moreover, the activity of NF-κB and the concentration of pro-inflammatory cytokines were determined by the ELISA method. In comparison with the control group, a threefold increase in the expression of miR-146a and NF-κB, and a twofold decrease in the expression of TRAF6 were observed in the sciatic nerve of diabetic rats. Furthermore, the NF-κB activity and the concentration of TNF-α, interleukin 6 (IL-6), and interleukin 1β (IL-1β) in the sciatic nerve of diabetic rats were higher than in those of control counterparts. These results suggest that a defect in the NF-кB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy. PMID:25567745

  4. Interrupted E2F1-miR-34c-SCF negative feedback loop by hyper-methylation promotes colorectal cancer cell proliferation.

    PubMed

    Yang, Shu; Wu, Bo; Sun, Haimei; Ji, Fengqing; Sun, Tingyi; Zhao, Yan; Zhou, Deshan

    2015-01-01

    Tumour suppressor miR-34c deficiency resulted from hyper-methylation in its promoter is believed to be one of the main causes of colorectal cancer (CRC). Till date, miR-34c has been validated as a direct target of p53; but previous evidence suggested other transcription factor(s) must be involved in miR-34c transcription. In the present study, we in the first place identified a core promoter region (-1118 to -883 bp) of pre-miR-34c which was embedded within a hyper-methylated CpG island. Secondly, E2F1 promoted miR-34c transcription by physical interaction with the miR-34c promoter at site -897 to -889 bp. The transcriptional activating effect of E2F1 on miR-34c was in a p53 independent manner but profoundly promoted in the presence of p53 with exposure to 5-aza-2'-deoxycytidine (DAC). Thirdly, stem cell factor (SCF), a miR-34c target, was specifically reduced upon an introduction of E2F1 which lead to suppression of CRC cell proliferation. The E2F1-suppressed cell proliferation was partially abrogated by additional miR-34c inhibitor, indicating that the anti-proliferation effect of E2F1 was probably through activating miR-34c-SCF axis. Finally, SCF/KIT signalling increased E2F1 production by reducing its proteosomal degradation dependent on PI3K/Akt-GSK3β pathway. In conclusion, our results suggested the existence of E2F1-miR-34c-SCF negative feedback loop which was interrupted by the hyper-methylation of miR-34c promoter in CRC cells and increased cell proliferation. PMID:26704889

  5. Particle tracking code of simulating global RF feedback

    SciTech Connect

    Mestha, L.K.

    1991-09-01

    It is well known in the control community'' that a good feedback controller design is deeply rooted in the physics of the system. For example, when accelerating the beam we must keep several parameters under control so that the beam travels within the confined space. Important parameters include the frequency and phase of the rf signal, the dipole field, and the cavity voltage. Because errors in these parameters will progressively mislead the beam from its projected path in the tube, feedback loops are used to correct the behavior. Since the feedback loop feeds energy to the system, it changes the overall behavior of the system and may drive it to instability. Various types of controllers are used to stabilize the feedback loop. Integrating the beam physics with the feedback controllers allows us to carefully analyze the beam behavior. This will not only guarantee optimal performance but will also significantly enhance the ability of the beam control engineer to deal effectively with the interaction of various feedback loops. Motivated by this theme, we developed a simple one-particle tracking code to simulate particle behavior with feedback controllers. In order to achieve our fundamental objective, we can ask some key questions: What are the input and output parameters How can they be applied to the practical machine How can one interface the rf system dynamics such as the transfer characteristics of the rf cavities and phasing between the cavities Answers to these questions can be found by considering a simple case of a single cavity with one particle, tracking it turn-by-turn with appropriate initial conditions, then introducing constraints on crucial parameters. Critical parameters are rf frequency, phase, and amplitude once the dipole field has been given. These are arranged in the tracking code so that we can interface the feedback system controlling them.

  6. The Autoregulatory Feedback Loop of MicroRNA-21/Programmed Cell Death Protein 4/Activation Protein-1 (MiR-21/PDCD4/AP-1) as a Driving Force for Hepatic Fibrosis Development*

    PubMed Central

    Zhang, Zhengping; Zha, Yinhe; Hu, Wei; Huang, Zhen; Gao, Zhongfei; Zang, Yuhui; Chen, Jiangning; Dong, Lei; Zhang, Junfeng

    2013-01-01

    Sustained activation of hepatic stellate cells (HSCs) leads to hepatic fibrosis, which is characterized by excessive collagen production, and for which there is no available drug clinically. Despite tremendous progress, the cellular activities underlying HSC activation, especially the driving force in the perpetuation stage, are only partially understood. Recently, microRNA-21 (miR-21) has been found to be prevalently up-regulated during fibrogenesis in different tissues, although its detailed role needs to be further elucidated. In the present study, miR-21 expression was examined in human cirrhotic liver samples and in murine fibrotic livers induced by thioacetamide or carbon tetrachloride. A dramatic miR-21 increase was noted in activated HSCs. We further found that miR-21 maintained itself at constant high levels by using a microRNA-21/programmed cell death protein 4/activation protein-1 (miR-21/PDCD4/AP-1) feedback loop. Disrupting this loop with miR-21 antagomir or AP-1 inhibitors significantly suppressed fibrogenic activities in HSCs and ameliorated liver fibrosis. In contrast, reinforcing this loop with small interfering RNA (siRNA) against PDCD4 promoted fibrogenesis in HSCs. Further analysis indicated that the up-regulated miR-21 promoted the central transforming growth factor-β (TGF-β) signaling pathway underlying HSC activation. In summary, we suggest that the miR-21/PDCD4/AP-1 autoregulatory loop is one of the main driving forces for hepatic fibrosis progression. Targeting this aberrantly activated feedback loop may provide a new therapeutic strategy and facilitate drug discovery against hepatic fibrosis. PMID:24196965

  7. FOXP3 controls an miR-146/NFκB negative feedback loop that inhibits apoptosis in breast cancer cells

    PubMed Central

    Liu, Runhua; Liu, Cong; Chen, Dongquan; Yang, Wei-Hsiung; Liu, Xiuping; Liu, Chang-Gong; Dugas, Courtney M.; Tang, Fei; Zheng, Pan; Liu, Yang; Wang, Lizhong

    2015-01-01

    FOXP3 functions not only as the master regulator in regulatory T cells but also as an X-linked tumor suppressor. The tumor suppressive activity of FOXP3 has been observed in tumor initiation, but its role during tumor progression remains controversial. Moreover, the mechanism of FOXP3-mediated tumor suppressive activity remains largely unknown. Using chromatin immunoprecipitation sequencing, we identified a series of potential FOXP3-targeted microRNAs (miRs) in MCF7 cells. Notably, FOXP3 significantly induced the expression of miR-146a/b. In vitro, FOXP3-induced miR-146a/b prevented tumor cell proliferation and enhanced apoptosis. Functional analyses in vitro and in vivo revealed that FOXP3-induced miR-146a/b negatively regulate NF-κB activation by inhibiting the expression of IRAK1 and TRAF6. In chromatin immunoprecipitation assays, FOXP3 directly bound the promoter region of miR-146a but not of miR-146b, and FOXP3 interacted directly with NF-κB p65 to regulate an miR-146-NF-κB negative feedback regulation loop in normal breast epithelial and tumor cells, as demonstrated with luciferase reporter assays. Although FOXP3 significantly inhibited breast tumor growth and migration in vitro and metastasis in vivo, FOXP3-induced miR-146a/b contributed only to the inhibition of breast tumor growth. These data suggest that miR-146a/b contribute to FOXP3-mediated tumor suppression during tumor growth by triggering apoptosis. The identification of a FOXP3-miR-146-NF-κB axis provides an underlying mechanism for disruption of miR-146 family member expression and constitutive NF-κB activation in breast cancer cells. Linking the tumor suppressor function of FOXP3 to NF-κB activation reveals a potential therapeutic approach for cancers with FOXP3 defects. PMID:25712342

  8. Optical voltage reference

    DOEpatents

    Rankin, Richard; Kotter, Dale

    1994-01-01

    An optical voltage reference for providing an alternative to a battery source. The optical reference apparatus provides a temperature stable, high precision, isolated voltage reference through the use of optical isolation techniques to eliminate current and impedance coupling errors. Pulse rate frequency modulation is employed to eliminate errors in the optical transmission link while phase-lock feedback is employed to stabilize the frequency to voltage transfer function.

  9. Optical voltage reference

    DOEpatents

    Rankin, R.; Kotter, D.

    1994-04-26

    An optical voltage reference for providing an alternative to a battery source is described. The optical reference apparatus provides a temperature stable, high precision, isolated voltage reference through the use of optical isolation techniques to eliminate current and impedance coupling errors. Pulse rate frequency modulation is employed to eliminate errors in the optical transmission link while phase-lock feedback is employed to stabilize the frequency to voltage transfer function. 2 figures.

  10. MHD computation of feedback of resistive-shell instabilities in the reversed field pinch

    SciTech Connect

    Zita, E.J.; Prager, S.C. . Plasma Physics Research); Ho, Y.L.; Schnack, D.D )

    1992-05-01

    MHD computation demonstrates that feedback can sustain reversal and reduce loop voltage in resistive-shell reversed field pinch (RFP) plasmas. Edge feedback on {approximately}2R/a tearing modes resonant near axis is found to restore plasma parameters to nearly their levels with a close-fitting conducting shell. When original dynamo modes are stabilized, neighboring tearing modes grow to maintain the RFP dynamo more efficiently. This suggests that experimentally observed limits on RFP pulselengths to the order of the shell time can be overcome by applying feedback to a few helical modes.

  11. Feedback Augmented Sub-Ranging (FASR) Quantizer

    NASA Technical Reports Server (NTRS)

    Guilligan, Gerard

    2012-01-01

    This innovation is intended to reduce the size, power, and complexity of pipeline analog-to-digital converters (ADCs) that require high resolution and speed along with low power. Digitizers are important components in any application where analog signals (such as light, sound, temperature, etc.) need to be digitally processed. The innovation implements amplification of a sampled residual voltage in a switched capacitor amplifier stage that does not depend on charge redistribution. The result is less sensitive to capacitor mismatches that cause gain errors, which are the main limitation of such amplifiers in pipeline ADCs. The residual errors due to mismatch are reduced by at least a factor of 16, which is equivalent to at least 4 bits of improvement. The settling time is also faster because of a higher feedback factor. In traditional switched capacitor residue amplifiers, closed-loop amplification of a sampled and held residue signal is achieved by redistributing sampled charge onto a feedback capacitor around a high-gain transconductance amplifier. The residual charge that was sampled during the acquisition or sampling phase is stored on two or more capacitors, often equal in value or integral multiples of each other. During the hold or amplification phase, all of the charge is redistributed onto one capacitor in the feedback loop of the amplifier to produce an amplified voltage. The key error source is the non-ideal ratios of feedback and input capacitors caused by manufacturing tolerances, called mismatches. The mismatches cause non-ideal closed-loop gain, leading to higher differential non-linearity. Traditional solutions to the mismatch errors are to use larger capacitor values (than dictated by thermal noise requirements) and/or complex calibration schemes, both of which increase the die size and power dissipation. The key features of this innovation are (1) the elimination of the need for charge redistribution to achieve an accurate closed-loop gain of two, (2) a higher feedback factor in the amplifier stage giving a higher closed-loop bandwidth compared to the prior art, and (3) reduced requirement for calibration. The accuracy of the new amplifier is mainly limited by the sampling networks parasitic capacitances, which should be minimized in relation to the sampling capacitors.

  12. Low-Bandwidth Operation of TES-Based Bolometer Operation in a Resistance Locked Loop

    NASA Astrophysics Data System (ADS)

    van der Kuur, J.; Gottardi, L.; Akamatsu, H.; Bruijn, M.; den Hartog, R.; Hoevers, H.; Gao, J. R.; Hijmering, R.; Khosropanah, P.; Ridder, M.

    2014-08-01

    Operation of TES-based bolometers in a resistance locked loop (RLL), i.e. keeping the operating resistance constant by means of feedback on the bias voltage, provides a number of attractive properties for applications. In combination with frequency domain multiplexing, the technique reduces electrical cross talk, and provides a more detector load independent behaviour with respect to operation under standard voltage bias. This paper shows a quantitative estimation of the large signal properties under the RLL, and shows a comparison with the situation under voltage bias. Furthermore, an unorthodox, low-bandwidth mode of operation will be discussed, from the perspective of the electro-thermal stability in the RLL.

  13. Global Feedback Simulator

    SciTech Connect

    Carlos Serrano, Lawrence Doolittle

    2015-10-29

    GFS is a simulation engine that is used for the characterization of Accelerator performance parameters based on the machine layout, configuration and noise sources. It combines extensively tested Feedback models with a longitudinal phase space tracking simulator along with the interaction between the two via beam-based feedback using a computationally efficient simulation engine. The models include beam instrumentation, considerations on loop delays for in both the R and beam-based feedback loops, as well as the ability to inject noise (both correlated and uncorrelated) at different points of the machine including a full characterization of the electron gun performance parameters.

  14. Global Feedback Simulator

    Energy Science and Technology Software Center (ESTSC)

    2015-10-29

    GFS is a simulation engine that is used for the characterization of Accelerator performance parameters based on the machine layout, configuration and noise sources. It combines extensively tested Feedback models with a longitudinal phase space tracking simulator along with the interaction between the two via beam-based feedback using a computationally efficient simulation engine. The models include beam instrumentation, considerations on loop delays for in both the R and beam-based feedback loops, as well as themore » ability to inject noise (both correlated and uncorrelated) at different points of the machine including a full characterization of the electron gun performance parameters.« less

  15. Feedback control of waiting times

    NASA Astrophysics Data System (ADS)

    Brandes, Tobias; Emary, Clive

    2016-04-01

    Feedback loops are known as a versatile tool for controlling transport in small systems, which usually have large intrinsic fluctuations. Here we investigate the control of a temporal correlation function, the waiting-time distribution, under active and passive feedback conditions. We develop a general formalism and then specify to the simple unidirectional transport model, where we compare costs of open-loop and feedback control and use methods from optimal control theory to optimize waiting-time distributions.

  16. Single-Loop Antenna Control

    NASA Astrophysics Data System (ADS)

    Gawronski, W.

    2002-07-01

    This article presents a study of a single-loop antenna control system. A typical antenna control system consists of two feedback loops. The first one -- an inner loop -- is called a rate loop. It uses tachometers to control the drive rate. The second loop -- called a position loop -- uses encoders to control antenna position. The questions arise: Does one need two loops to control antenna motions? Can one achieve similar performance for a system with the position loop only? In order to answer these questions, we studied three types of antennas with a single-loop control: a rigid (or idealized) antenna in order to obtain initial insight into properties of the closed-loop antenna systems; a small antenna, 5 meters in diameter; and a large antenna, 34 meters in diameter. The study compares command following and rejection of wind disturbances of antennas with and without rate loops, and we show that both configurations are equivalent.

  17. Frequency-Offset Cartesian Feedback Based on Polyphase Difference Amplifiers

    PubMed Central

    Zanchi, Marta G.; Pauly, John M.; Scott, Greig C.

    2010-01-01

    A modified Cartesian feedback method called “frequency-offset Cartesian feedback” and based on polyphase difference amplifiers is described that significantly reduces the problems associated with quadrature errors and DC-offsets in classic Cartesian feedback power amplifier control systems. In this method, the reference input and feedback signals are down-converted and compared at a low intermediate frequency (IF) instead of at DC. The polyphase difference amplifiers create a complex control bandwidth centered at this low IF, which is typically offset from DC by 200–1500 kHz. Consequently, the loop gain peak does not overlap DC where voltage offsets, drift, and local oscillator leakage create errors. Moreover, quadrature mismatch errors are significantly attenuated in the control bandwidth. Since the polyphase amplifiers selectively amplify the complex signals characterized by a +90° phase relationship representing positive frequency signals, the control system operates somewhat like single sideband (SSB) modulation. However, the approach still allows the same modulation bandwidth control as classic Cartesian feedback. In this paper, the behavior of the polyphase difference amplifier is described through both the results of simulations, based on a theoretical analysis of their architecture, and experiments. We then describe our first printed circuit board prototype of a frequency-offset Cartesian feedback transmitter and its performance in open and closed loop configuration. This approach should be especially useful in magnetic resonance imaging transmit array systems. PMID:20814450

  18. Static VAR Compensator-Based Voltage Regulation for Variable-Speed Prime Mover Coupled Single-Phase Self-Excited Induction Generator

    NASA Astrophysics Data System (ADS)

    Ahmed, Tarek; Noro, Osamu; Hiraki, Eiji; Nakaoka, Mutsuo

    In this paper, the single-phase static VAR compensator (SVC) is applied to regulate and stabilize smoothly the generated output voltage of the single-phase self-excited induction generator (single-phase SEIG) driven by a variable-speed prime mover (VSPM) under the conditions of inductive load variations and prime mover speed changes. The conventional fixed gain PI controller-based feedback control scheme is employed to adjust the equivalent capacitance of the single-phase SVC composed of the fixed excitation capacitor (FC) in parallel with the thyristor switched capacitor (TSC) and the thyristor controlled reactor TCR. A PI closed-loop feedback voltage control scheme based on the SVC for the single-phase SEIG coupled by a VSPM prototype set-up is established. The closed-loop feedback output voltage responses in the single-phase SEIG coupled by a VSPM with different inductive load variations using the single-phase SVC with the PI controller are considered and discussed herein. Based on the SVC with the PI controller closed-loop feedback voltage regulation scheme, the experimental results for the single-phase SEIG driven by a VSPM are illustrated and proved its practical effectiveness in terms of the fast response and the high performances.

  19. Theoretical Design of a Depolarized Interferometric Fiber-Optic Gyroscope (IFOG) on SMF-28 Single-Mode Standard Optical Fiber Based on Closed-Loop Sinusoidal Phase Modulation with Serrodyne Feedback Phase Modulation Using Simulation Tools for Tactical and Industrial Grade Applications

    PubMed Central

    Pérez, Ramón José; Álvarez, Ignacio; Enguita, José María

    2016-01-01

    This article presents, by means of computational simulation tools, a full analysis and design of an Interferometric Fiber-Optic Gyroscope (IFOG) prototype based on a closed-loop configuration with sinusoidal bias phase- modulation. The complete design of the different blocks, optical and electronic, is presented, including some novelties as the sinusoidal bias phase-modulation and the use of an integrator to generate the serrodyne phase-modulation signal. The paper includes detailed calculation of most parameter values, and the plots of the resulting signals obtained from simulation tools. The design is focused in the use of a standard single-mode optical fiber, allowing a cost competitive implementation compared to commercial IFOG, at the expense of reduced sensitivity. The design contains an IFOG model that accomplishes tactical and industrial grade applications (sensitivity ≤ 0.055 °/h). This design presents two important properties: (1) an optical subsystem with advanced conception: depolarization of the optical wave by means of Lyot depolarizers, which allows to use a sensing coil made by standard optical fiber, instead by polarization maintaining fiber, which supposes consequent cost savings and (2) a novel and simple electronic design that incorporates a linear analog integrator with reset in feedback chain, this integrator generating a serrodyne voltage-wave to apply to Phase-Modulator (PM), so that it will be obtained the interferometric phase cancellation. This particular feedback design with sawtooth-wave generated signal for a closed-loop configuration with sinusoidal bias phase modulation has not been reported till now in the scientific literature and supposes a considerable simplification with regard to previous designs based on similar configurations. The sensing coil consists of an 8 cm average diameter spool that contains 300 m of standard single-mode optical-fiber (SMF-28 type) realized by quadrupolar winding. The working wavelength will be 1310 nm. The theoretical calculated values of threshold sensitivity and dynamic range for this prototype are 0.052 °/h and 101.38 dB (from ±1.164 × 10−5 °/s up to ±78.19 °/s), respectively. The Scale-Factor (SF) non-linearity for this model is 5.404% relative to full scale, this value being obtained from data simulation results. PMID:27128924

  20. Theoretical Design of a Depolarized Interferometric Fiber-Optic Gyroscope (IFOG) on SMF-28 Single-Mode Standard Optical Fiber Based on Closed-Loop Sinusoidal Phase Modulation with Serrodyne Feedback Phase Modulation Using Simulation Tools for Tactical and Industrial Grade Applications.

    PubMed

    Pérez, Ramón José; Álvarez, Ignacio; Enguita, José María

    2016-01-01

    This article presents, by means of computational simulation tools, a full analysis and design of an Interferometric Fiber-Optic Gyroscope (IFOG) prototype based on a closed-loop configuration with sinusoidal bias phase- modulation. The complete design of the different blocks, optical and electronic, is presented, including some novelties as the sinusoidal bias phase-modulation and the use of an integrator to generate the serrodyne phase-modulation signal. The paper includes detailed calculation of most parameter values, and the plots of the resulting signals obtained from simulation tools. The design is focused in the use of a standard single-mode optical fiber, allowing a cost competitive implementation compared to commercial IFOG, at the expense of reduced sensitivity. The design contains an IFOG model that accomplishes tactical and industrial grade applications (sensitivity ≤ 0.055 °/h). This design presents two important properties: (1) an optical subsystem with advanced conception: depolarization of the optical wave by means of Lyot depolarizers, which allows to use a sensing coil made by standard optical fiber, instead by polarization maintaining fiber, which supposes consequent cost savings and (2) a novel and simple electronic design that incorporates a linear analog integrator with reset in feedback chain, this integrator generating a serrodyne voltage-wave to apply to Phase-Modulator (PM), so that it will be obtained the interferometric phase cancellation. This particular feedback design with sawtooth-wave generated signal for a closed-loop configuration with sinusoidal bias phase modulation has not been reported till now in the scientific literature and supposes a considerable simplification with regard to previous designs based on similar configurations. The sensing coil consists of an 8 cm average diameter spool that contains 300 m of standard single-mode optical-fiber (SMF-28 type) realized by quadrupolar winding. The working wavelength will be 1310 nm. The theoretical calculated values of threshold sensitivity and dynamic range for this prototype are 0.052 °/h and 101.38 dB (from ±1.164 × 10(-5) °/s up to ±78.19 °/s), respectively. The Scale-Factor (SF) non-linearity for this model is 5.404% relative to full scale, this value being obtained from data simulation results. PMID:27128924

  1. A synthetic gene circuit for measuring autoregulatory feedback control.

    PubMed

    Schikora-Tamarit, Miquel Àngel; Toscano-Ochoa, Carlos; Domingo Espinós, Júlia; Espinar, Lorena; Carey, Lucas B

    2016-04-18

    Autoregulatory feedback loops occur in the regulation of molecules ranging from ATP to MAP kinases to zinc. Negative feedback loops can increase a system's robustness, while positive feedback loops can mediate transitions between cell states. Recent genome-wide experimental and computational studies predict hundreds of novel feedback loops. However, not all physical interactions are regulatory, and many experimental methods cannot detect self-interactions. Our understanding of regulatory feedback loops is therefore hampered by the lack of high-throughput methods to experimentally quantify the presence, strength and temporal dynamics of autoregulatory feedback loops. Here we present a mathematical and experimental framework for high-throughput quantification of feedback regulation and apply it to RNA binding proteins (RBPs) in yeast. Our method is able to determine the existence of both direct and indirect positive and negative feedback loops, and to quantify the strength of these loops. We experimentally validate our model using two RBPs which lack native feedback loops and by the introduction of synthetic feedback loops. We find that RBP Puf3 does not natively participate in any direct or indirect feedback regulation, but that replacing the native 3'UTR with that of COX17 generates an auto-regulatory negative feedback loop which reduces gene expression noise. Likewise, RBP Pub1 does not natively participate in any feedback loops, but a synthetic positive feedback loop involving Pub1 results in increased expression noise. Our results demonstrate a synthetic experimental system for quantifying the existence and strength of feedback loops using a combination of high-throughput experiments and mathematical modeling. This system will be of great use in measuring auto-regulatory feedback by RNA binding proteins, a regulatory motif that is difficult to quantify using existing high-throughput methods. PMID:26728081

  2. Down-regulation of miR-129-5p via the Twist1-Snail feedback loop stimulates the epithelial-mesenchymal transition and is associated with poor prognosis in breast cancer

    PubMed Central

    Yu, Yue; Zhao, Ying; Sun, Xiao-Hu; Ge, Jie; Zhang, Bin; Wang, Xin; Cao, Xu-Chen

    2015-01-01

    The epithelial to mesenchymal transition (EMT) plays a pivotal role in breast cancer progression. We found that overexpression of miR-129-5p reversed EMT, whereas depletion of miR-129-5p induced EMT in breast cancer cells. We demonstrated that Twist1 is a direct target of miR-129-5p. Both Twist1 and Snail transcriptionally suppressed miR-129-5p expression. Levels of miR-129-5p were low in breast cancer tissues. miR-129-5p down-regulation correlated with advanced clinical stage and poor prognosis in patients with breast cancer. miR-129-5p expression negatively correlated with Twist1 and Snail expression. Thus, miR-129-5p down-regulation fosters EMT in breast cancer by increasing Twist1-Snail and activating a negative feedback loop. PMID:26460733

  3. Regenerative feedback resonant circuit

    DOEpatents

    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.

  4. Audio Feedback -- Better Feedback?

    ERIC Educational Resources Information Center

    Voelkel, Susanne; Mello, Luciane V.

    2014-01-01

    National Student Survey (NSS) results show that many students are dissatisfied with the amount and quality of feedback they get for their work. This study reports on two case studies in which we tried to address these issues by introducing audio feedback to one undergraduate (UG) and one postgraduate (PG) class, respectively. In case study one…

  5. Voltage-Controlled Oscillator

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Integrated Component Systems, Inc. incorporated information from a NASA Tech Briefs article into a voltage-controlled oscillator it designed for a customer. The company then applied the technology to its series of phase-locked loop synthesizers, which offer superior phase noise performance.

  6. The ZEB1 transcription factor acts in a negative feedback loop with miR200 downstream of Ras and Rb1 to regulate Bmi1 expression.

    PubMed

    Liu, Yongqing; Sánchez-Tilló, Ester; Lu, Xiaoqin; Huang, Li; Clem, Brian; Telang, Sucheta; Jenson, Alfred B; Cuatrecasas, Miriam; Chesney, Jason; Postigo, Antonio; Dean, Douglas C

    2014-02-14

    Ras mutations are frequent in cancer cells where they drive proliferation and resistance to apoptosis. However in primary cells, mutant Ras instead can cause oncogene-induced senescence, a tumor suppressor function linked to repression of the polycomb factor Bmi1, which normally regulates cell cycle inhibitory cyclin-dependent kinase inhibitors (cdki). It is unclear how Ras causes repression of Bmi1 in primary cells to suppress tumor formation while inducing the gene in cancer cells to drive tumor progression. Ras also induces the EMT transcription factor ZEB1 to trigger tumor invasion and metastasis. Beyond its well-documented role in EMT, ZEB1 is important for maintaining repression of cdki. Indeed, heterozygous mutation of ZEB1 is sufficient for elevated cdki expression, leading to premature senescence of primary cells. A similar phenotype is evident with Bmi1 mutation. We show that activation of Rb1 in response to mutant Ras causes dominant repression of ZEB1 in primary cells, but loss of the Rb1 pathway is a hallmark of cancer cells and in the absence of such Rb1 repression Ras induces ZEB1 in cancer cells. ZEB1 represses miR-200 in the context of a mutual repression loop. Because miR-200 represses Bmi1, induction of ZEB1 leads to induction of Bmi1. Rb1 pathway status then dictates the opposing effects of mutant Ras on the ZEB1-miR-200 loop in primary versus cancer cells. This loop not only triggers EMT, surprisingly we show it acts downstream of Ras to regulate Bmi1 expression and thus the critical decision between oncogene-induced senescence and tumor initiation. PMID:24371144

  7. Open-loop Band excitation Kelvin Probe Force Microscopy

    SciTech Connect

    Guo, Senli; Kalinin, Sergei V; Jesse, Stephen

    2012-01-01

    A multidimensional scanning probe microscopy approach for quantitative, cross-talk free mapping of surface electrostatic properties is demonstrated. Open-loop band excitation Kelvin probe force microscopy (OL BE KPFM) probes the full response-frequency-potential surface at each pixel at standard imaging rates. The subsequent analysis reconstructs work function, tip surface capacitance gradient and resonant frequency maps, obviating feedback-related artifacts. OL BE KPFM imaging is demonstrated for several materials systems with topographic, potential and combined contrast. This approach combines the features of both frequency and amplitude KPFM and allows complete decoupling of topographic and voltage contributions to the KPFM signal.

  8. A prototype framework for models of socio-hydrology: identification of key feedback loops with application to two Australian case-studies

    NASA Astrophysics Data System (ADS)

    Elshafei, Y.; Sivapalan, M.; Tonts, M.; Hipsey, M. R.

    2014-01-01

    It is increasingly acknowledged that, in order to sustainably manage global freshwater resources, it is critical that we better understand the nature of human-hydrology interactions at the broader catchment system-scale. Yet to date, a generic conceptual framework for building models of catchment systems that include adequate representation of socioeconomic systems - and the dynamic feedbacks between human and natural systems - has remained elusive. In an attempt to work towards such a model, this paper outlines a generic framework for a model of socio-hydrology that posits a novel construct, a composite Community Sensitivity state variable, as a key link to elucidate the drivers of behavioural response in a hydrological context. The framework provides for both macro-scale contextual parameters, which allow it to be applied across climate, socioeconomic and political gradients, and catchment-specific conditions, by way of tailored "closure relationships", in order to ensure that site-specific and application-specific contexts of socio-hydrologic problems can be accommodated. To demonstrate how such a framework would be applied, two different socio-hydrological case studies, taken from the Australian experience, are presented and discussed. It is envisioned that the application of this framework across study sites and gradients will aid in developing our understanding of the fundamental interactions and feedbacks in such complex human-hydrology systems, and allow hydrologists to participate in the growing field of social-ecological systems modelling.

  9. E-beam high voltage switching power supply

    DOEpatents

    Shimer, D.W.; Lange, A.C.

    1997-03-11

    A high power, solid state power supply is described for producing a controllable, constant high voltage output under varying and arcing loads suitable for powering an electron beam gun or other ion source. The present power supply is most useful for outputs in a range of about 100-400 kW or more. The power supply is comprised of a plurality of discrete switching type dc-dc converter modules, each comprising a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, and an output rectifier for producing a dc voltage at the output of each module. The inputs to the converter modules are fed from a common dc rectifier/filter and are linked together in parallel through decoupling networks to suppress high frequency input interactions. The outputs of the converter modules are linked together in series and connected to the input of the transmission line to the load through a decoupling and line matching network. The dc-dc converter modules are phase activated such that for n modules, each module is activated equally 360{degree}/n out of phase with respect to a successive module. The phased activation of the converter modules, combined with the square current waveforms out of the step up transformers, allows the power supply to operate with greatly reduced output capacitance values which minimizes the stored energy available for discharge into an electron beam gun or the like during arcing. The present power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle using simulated voltage feedback signals and voltage feedback loops. Circuitry is also provided for sensing incipient arc currents reflected at the output of the power supply and for simultaneously decoupling the power supply circuitry from the arcing load. 7 figs.

  10. E-beam high voltage switching power supply

    DOEpatents

    Shimer, Daniel W.; Lange, Arnold C.

    1997-01-01

    A high power, solid state power supply is described for producing a controllable, constant high voltage output under varying and arcing loads suitable for powering an electron beam gun or other ion source. The present power supply is most useful for outputs in a range of about 100-400 kW or more. The power supply is comprised of a plurality of discrete switching type dc-dc converter modules, each comprising a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, and an output rectifier for producing a dc voltage at the output of each module. The inputs to the converter modules are fed from a common dc rectifier/filter and are linked together in parallel through decoupling networks to suppress high frequency input interactions. The outputs of the converter modules are linked together in series and connected to the input of the transmission line to the load through a decoupling and line matching network. The dc-dc converter modules are phase activated such that for n modules, each module is activated equally 360.degree./n out of phase with respect to a successive module. The phased activation of the converter modules, combined with the square current waveforms out of the step up transformers, allows the power supply to operate with greatly reduced output capacitance values which minimizes the stored energy available for discharge into an electron beam gun or the like during arcing. The present power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle using simulated voltage feedback signals and voltage feedback loops. Circuitry is also provided for sensing incipient arc currents reflected at the output of the power supply and for simultaneously decoupling the power supply circuitry from the arcing load.

  11. Regulative Loops, Step Loops and Task Loops

    ERIC Educational Resources Information Center

    VanLehn, Kurt

    2016-01-01

    This commentary suggests a generalization of the conception of the behavior of tutoring systems, which the target article characterized as having an outer loop that was executed once per task and an inner loop that was executed once per step of the task. A more general conception sees these two loops as instances of regulative loops, which…

  12. IFN-λ Inhibits MiR-122 Transcription through a Stat3-HNF4α Inflammatory Feedback Loop in an IFN-α Resistant HCV Cell Culture System

    PubMed Central

    Aboulnasr, Fatma; Hazari, Sidhartha; Nayak, Satyam; Chandra, Partha K.; Panigrahi, Rajesh; Ferraris, Pauline; Chava, Srinivas; Kurt, Ramazan; Song, Kyongsub; Dash, Asha; Balart, Luis A.; Garry, Robert F.; Wu, Tong; Dash, Srikanta

    2015-01-01

    Background HCV replication in persistently infected cell culture remains resistant to IFN-α/RBV combination treatment, whereas IFN-λ1 induces viral clearance. The antiviral mechanisms by which IFN-λ1 induces sustained HCV clearance have not been determined. Aim To investigate the mechanisms by which IFN-λ clears HCV replication in an HCV cell culture model. Methods IFN-α sensitive (S3-GFP) and resistant (R4-GFP) cells were treated with equivalent concentrations of either IFN-α or IFN-λ. The relative antiviral effects of IFN-α and IFN-λ1 were compared by measuring the HCV replication, quantification of HCV-GFP expression by flow cytometry, and viral RNA levels by real time RT-PCR. Activation of Jak-Stat signaling, interferon stimulated gene (ISG) expression, and miRNA-122 transcription in S3-GFP and R4-GFP cells were examined. Results We have shown that IFN-λ1 induces HCV clearance in IFN-α resistant and sensitive replicon cell lines in a dose dependent manner through Jak-Stat signaling, and induces STAT 1 and STAT 2 activation, ISRE-luciferase promoter activation and ISG expression. Stat 3 activation is also involved in IFN-λ1 induced antiviral activity in HCV cell culture. IFN-λ1 induced Stat 3 phosphorylation reduces the expression of hepatocyte nuclear factor 4 alpha (HNF4α) through miR-24 in R4-GFP cells. Reduced expression of HNF4α is associated with decreased expression of miR-122 resulting in an anti-HCV effect. Northern blot analysis confirms that IFN-λ1 reduces miR-122 levels in R4-GFP cells. Our results indicate that IFN-λ1 activates the Stat 3-HNF4α feedback inflammatory loop to inhibit miR-122 transcription in HCV cell culture. Conclusions In addition to the classical Jak–Stat antiviral signaling pathway, IFN-λ1 inhibits HCV replication through the suppression of miRNA-122 transcription via an inflammatory Stat 3–HNF4α feedback loop. Inflammatory feedback circuits activated by IFNs during chronic inflammation expose non-responders to the risk of hepatocellular carcinoma. PMID:26657215

  13. Regulation of BRAF protein stability by a negative feedback loop involving the MEK-ERK pathway but not the FBXW7 tumour suppressor.

    PubMed

    Hernandez, Maria Aguilar; Patel, Bipin; Hey, Fiona; Giblett, Susan; Davis, Hayley; Pritchard, Catrin

    2016-06-01

    The (V600E)BRAF oncogenic mutation is detected in a wide range of human cancers and induces hyperactivation of the downstream MEK-ERK signalling cascade. Although output of the BRAF-MEK-ERK pathway is regulated by feed-forward RAF activity, feedback control also plays an important role. One such feedback pathway has been identified in Caenorhabditis elegans and involves ERK-mediated phosphorylation of BRAF within a CDC4 phosphodegron (CPD), targeting BRAF for degradation via CDC4 (also known as FBXW7), a component of the SKP1/CUL1/F-box (SCF) E3 ubiquitin ligase complex. Here we investigate this pathway in mammalian cells. Short-term expression of autochthonous (V600E)BRAF in mouse embryonic fibroblasts (MEFs) leads to down-regulation of BRAF protein levels in a proteasome-dependent manner and (V600E)BRAF has a reduced half-life compared to (WT)BRAF in HEK293(T) cells. These effects were reversed by treatment with the MEK inhibitor PD184352. We have identified the equivalent CPD at residues 400-405 in human BRAF and have found that mutation of ERK phosphorylation sites at residues T401 and S405 in (V600E)BRAF increases the half-life of the protein. While BRAF and FBXW7 co-immunoprecipitated, the overexpression of FBXW7 did not influence the half-life of either (WT)BRAF or (V600E)BRAF. Furthermore, disruption of the substrate-binding site of mouse FBXW7 using the R482Q mutation did not affect the interaction with BRAF and the expression levels of (WT)BRAF and (V600E)BRAF were not altered in MEFs derived from mice with the homozygous knockin (R482Q)FBXW7 mutation. Overall these data confirm the existence of a negative feedback pathway by which BRAF protein stability is regulated by ERK. However, unlike the situation in C. elegans, FBXW7 does not play a unique role in mediating subsequent BRAF degradation. PMID:26898828

  14. Designing Genetic Feedback Controllers.

    PubMed

    Harris, Andreas W K; Dolan, James A; Kelly, Ciarán L; Anderson, James; Papachristodoulou, Antonis

    2015-08-01

    By incorporating feedback around systems we wish to manipulate, it is possible to improve their performance and robustness properties to meet pre-specified design objectives. For decades control engineers have been successfully implementing feedback controllers for complex mechanical and electrical systems such as aircraft and sports cars. Natural biological systems use feedback extensively for regulation and adaptation but apart from the most basic designs, there is no systematic framework for designing feedback controllers in Synthetic Biology. In this paper we describe how classical approaches from linear control theory can be used to close the loop. This includes the design of genetic circuits using feedback control and the presentation of a biological phase lag controller. PMID:26390502

  15. Development of a closed-loop feedback system for real-time control of a high-dimensional Brain Machine Interface.

    PubMed

    Putrino, David; Wong, Yan T; Vigeral, Mariana; Pesaran, Bijan

    2012-01-01

    As the field of neural prosthetics advances, Brain Machine Interface (BMI) design requires the development of virtual prostheses that allow decoding algorithms to be tested for efficacy in a time- and cost-efficient manner. Using an x-ray and MRI-guided skeletal reconstruction, and a graphic artist's rendering of an anatomically correct macaque upper limb, we created a virtual avatar capable of independent movement across 27 degrees-of-freedom (DOF). Using a custom software interface, we animated the avatar's movements in real-time using kinematic data acquired from awake, behaving macaque subjects using a 16 camera motion capture system. Using this system, we demonstrate real-time, closed-loop control of up to 27 DOFs in a virtual prosthetic device. Thus, we describe a practical method of testing the efficacy of high-complexity BMI decoding algorithms without the expense of fabricating a physical prosthetic. PMID:23366944

  16. Model-based feedback control of a microfluidic electroporation system

    NASA Astrophysics Data System (ADS)

    Ghadami, M.; Mahjoob, M. J.; Shagoshtasbi, H.; Lee, Y.-K.

    2013-12-01

    This paper describes new model-based feedback control method used for a single-cell microfluidic electroporation (EP) system. For this purpose, a new four-state nonlinear model has been developed to describe dynamics of a micro-channel electroporation system. EP measured current response is then used to verify the efficiency of the proposed new EP model. Consequently, two feedback control methods, namely, proportional-integral-derivative controller and model predictive controller have been applied to regulate the key states (i.e. transmembrane voltage (Vm) and nano-electropore radius (r)) in the EP model. Numerical simulations of static and dynamic responses of the two critical states, Vm and r, show that feedback control can improve the cell viability and EP efficiency compared to the open-loop system. In the experimental phase, a fabricated micro-EP chip with integrated Coulter counter is used to define the cell-size-dependent parameters of the EP model and electroporation of HeLa cells. In this phase, the EP model is also inserted into LabView software's environment to estimate the value of transmembrane voltage during the experiment. Variation of the external applied voltage derived from experimental result was in good adaptation with its equivalent theoretical values.

  17. The dc-to-dc converters employing staggered-phase power switches with two-loop control

    NASA Technical Reports Server (NTRS)

    Wester, G. W. (Inventor)

    1976-01-01

    A switched inductor voltage is coupled to a sense winding in each phase, and all sense windings are connected in series to one of two feedback loops to provide a signal that indicates when one of the power switches is on as the principal determinant of switching instants. A sequencer is triggered each time a pulse generator is triggered to turn on a different power switch in sequence at each switching instant.

  18. The Perceptual Characteristics of Voice-Hallucinations in Deaf People: Insights into the Nature of Subvocal Thought and Sensory Feedback Loops

    PubMed Central

    Atkinson, Joanna R.

    2006-01-01

    The study of voice-hallucinations in deaf individuals, who exploit the visuomotor rather than auditory modality for communication, provides rare insight into the relationship between sensory experience and how “voices” are perceived. Relatively little is known about the perceptual characteristics of voice-hallucinations in congenitally deaf people who use lip-reading or sign language as their preferred means of communication. The existing literature on hallucinations in deaf people is reviewed, alongside consideration of how such phenomena may fit into explanatory subvocal articulation hypotheses proposed for auditory verbal hallucinations in hearing people. It is suggested that a failure in subvocal articulation processes may account for voice-hallucinations in both hearing and deaf people but that the distinct way in which hallucinations are experienced may be due to differences in a sensory feedback component, which is influenced by both auditory deprivation and language modality. This article highlights how the study of deaf people may inform wider understanding of auditory verbal hallucinations and subvocal processes generally. PMID:16510696

  19. The perceptual characteristics of voice-hallucinations in deaf people: insights into the nature of subvocal thought and sensory feedback loops.

    PubMed

    Atkinson, Joanna R

    2006-10-01

    The study of voice-hallucinations in deaf individuals, who exploit the visuomotor rather than auditory modality for communication, provides rare insight into the relationship between sensory experience and how "voices" are perceived. Relatively little is known about the perceptual characteristics of voice-hallucinations in congenitally deaf people who use lip-reading or sign language as their preferred means of communication. The existing literature on hallucinations in deaf people is reviewed, alongside consideration of how such phenomena may fit into explanatory subvocal articulation hypotheses proposed for auditory verbal hallucinations in hearing people. It is suggested that a failure in subvocal articulation processes may account for voice-hallucinations in both hearing and deaf people but that the distinct way in which hallucinations are experienced may be due to differences in a sensory feedback component, which is influenced by both auditory deprivation and language modality. This article highlights how the study of deaf people may inform wider understanding of auditory verbal hallucinations and subvocal processes generally. PMID:16510696

  20. Brain-midgut cross-talk and autocrine metabolastat via the sNPF/CCAP negative feed-back loop in the American cockroach, Periplaneta americana.

    PubMed

    Mikani, Azam; Watari, Yasuhiko; Takeda, Makio

    2015-12-01

    Immunohistochemical reactivities against short neuropeptide F (sNPF-ir) and crustacean cardioactive peptide (CCAP-ir) were detected in both the brain-subesophageal ganglion (Br-SOG) and midgut epithelial cells of the male American cockroach, Periplaneta americana. Four weeks of starvation increased the number of sNPF-ir cells and decreased the CCAP-ir cells in the Br-SOG, whereas refeeding reversed these effects. The contents of sNPF in the Br-SOG, midgut and hemolymph titer decreased in response to an injection of CCAP into the hemocoel of normally fed male cockroaches, while CCAP titers/contents decreased in response to an injection of sNPF. The results of a double-labeling experiment demonstrated that sNPF-ir co-existed in CCAP-ir cells in the pars intercerebralis (PI), dorsolateral region of protocerebrum (DL), deutocerebrum (De) and SOG. sNPF-ir and CCAP-ir were also colocalized in the midgut. sNPF and CCAP are neuropeptides and midgut factors that interact with each other. Since the two peptides are known to be secreted by identical cells that affect each other, this constitutes autocrine negative feedback regulation for a quick response to food accessibility/inaccessibility. These peptides not only constitute the switch in the digestive mechanism but also couple digestive adaptation with behavior. A CCAP injection suppressed locomotor activity when cockroaches were starved, whereas sNPF activated it when they were fed. PMID:26178071

  1. LIM Homeobox 8 (Lhx8) Is a Key Regulator of the Cholinergic Neuronal Function via a Tropomyosin Receptor Kinase A (TrkA)-mediated Positive Feedback Loop*

    PubMed Central

    Tomioka, Takeyasu; Shimazaki, Takuya; Yamauchi, Toshihiko; Oki, Toru; Ohgoh, Makoto; Okano, Hideyuki

    2014-01-01

    Basal forebrain cholinergic neurons play an important role in cognitive functions such as learning and memory, and they are affected in several neurodegenerative diseases, including Alzheimer disease and Down syndrome. Despite their functional importance, the molecular mechanisms of functional maturation and maintenance of these cholinergic neurons after the differentiation stage have not been fully elucidated. This study demonstrates that the LIM homeobox 8 (Lhx8) transcription factor regulates cholinergic function in rat septal cholinergic neurons in primary cultures from E18.5 embryos and in the adult brain. Lhx8 expression modulated tropomyosin receptor kinase A (TrkA) expression in septal cholinergic neurons in vitro and in vivo, resulting in regulated acetylcholine release as an index of cholinergic function. In addition, Lhx8 expression and function were regulated by nerve growth factor (NGF), and the effect of NGF was potentiated by Lhx8-induced TrkA expression. Together, our findings suggest that positive feedback regulation between Lhx8, TrkA, and NGF is an important regulatory mechanism for cholinergic functions of the septum. PMID:24265310

  2. A positive feedback loop of p53/miR-19/TP53INP1 modulates pancreatic cancer cell proliferation and apoptosis.

    PubMed

    Wang, Xiaofang; Wang, Lei; Mo, Qingjiang; Jia, Ankui; Dong, Yuqian; Wang, Guoqiang

    2016-01-01

    Pancreatic cancer is a common malignancy whose prognosis and treatment of pancreatic cancer is extremely poor, with only 20% of patients reaching two years of survival. Previous findings have shown that the tumor suppressor p53 is involved in the development of various types of cancer, including pancreatic cancer. Additionally, p53 is able to activate TP53INP1 transcription by regulating several phenotypes of cancer cells. Using gain and loss-of-function assays, the aim of the present study was to examine the relationships between miR-19a/b and cancer development as well as potential underlying mechanisms. The results showed that miR-19a/b identified a positive feedback regulation of p53/TP53INP1 axis. Additionally, p53 upregulated the TP53INP1 level in pancreatic cancer cells. However, overexpressed miR-19a/b partially restored the TP53 function in the pancreatic cancer cells while miR-19a/b downregulated TP53INP1 protein by directly targeting 3'UTR of its mRNA at the post-transcriptional level. In addition, the patient tissues identified that the miR-19a/b level in pancreatic cancer tissues was conversely correlated with TP53 and TP53INP1 expression. The results provide evidence for revealing the molecular mechanism involved in the development of pancreatic cancer and may be useful in the identification of new therapeutic targets for pancreatic cancer. PMID:26531836

  3. Data-aided carrier tracking loops

    NASA Technical Reports Server (NTRS)

    Lindsey, W. C.; Simon, M. K. (Inventor)

    1973-01-01

    The characteristics of a data-aided carrier tracking loop are discussed. The loop signal to noise ratio is improved in a phase-locked loop used for tracking a carrier an angle modulated communications system by a quadrature channel added to the phase locked loop. A d.c. signal derived from the quadrature channel is added to the signal fed back to the voltage controlled oscillator in the otherwise conventional phase-locked loop.

  4. A direct current superconducting quantum interference device gradiometer with a digital signal processor controlled flux-locked loop and comparison with a conventional analog feedback scheme

    SciTech Connect

    Kung, P.J.; Bracht, R.R.; Flynn, E.R.; Lewis, P.S.

    1996-01-01

    A double-washer dc superconducting quantum interference device (SQUID) gradiometer with a flux-locked loop (FLL) based on a digital signal processor (DSP) has been developed for biomagnetic applications. All of the analog electronics in the conventional FLL are replaced and implemented by the DSP except for the low-noise field-effect transistor preamplifier at the front end of the signal recovery components. The DSP performs the signal demodulation by synchronously sampling the recovered signals and applying the appropriate full wave rectification. The signals are then integrated, filtered, and applied to the output. At 4.2 K, the white flux noise of the gradiometer measured in a DSP FLL mode is about 4{mu}{phi}{sub 0}/{radical}Hz and the noise at 1 Hz is 13 {mu}{phi}{sub 0}/{radical}Hz. The corresponding noise levels in the gradiometer operated by the conventional FLL are 1.8 and 3{mu}{phi}{sub 0}/{radical}Hz. The poorer system performance in the DSP FLL compared to the analog FLL is mainly caused by the ambient field noise and interference signals picked up through the connecting cables. Additional noise is also added to the overall noise floor by the instruments employed in the DSP system in the present prototype setup. Further improvement in the noise characteristics and the dynamic behavior of the DSP SQUID gradiometer is expected when a better configuration of DSP with the associated I/O devices is implemented. Additional improvements of the DSP programs are expected by incorporating higher-order integration, adaptive control, and noise reduction schemes. {copyright} {ital 1996 American Institute of Physics.}

  5. STABILITY OF HIGH VOLTAGE MODULATORS FOR NONLINEAR LOADS

    SciTech Connect

    PAWLEY,J.C; TOOKER,J; PEAVY,J; CARY,W.P; NEREM,A; HOYT,D; LOHR,J

    2003-10-01

    OAK-B135 Gyrotrons have a nonlinear voltage--current characteristic such that the small signal or ac impedance changes as operational voltage and currents are reached. The ac impedance determines the stability of a voltage or current control system. this can become particularly challenging when several gyrotron are connected in parallel to a single modulator. With all gyrotrons hooked to a common ground, large current loops can be generated as well as non-canceling currents in individual coaxial lines. These inequalities can provide the required feedback impulse to start an oscillation condition in the power system for the tubes. Recent operation of two CPI 110 GHz gyrotrons in the MN class from a single modulator on DIII-D has shown instability in the power system. An oscillation in the drive current occurs at various points in the ramp up and flat top portions of the 80 kV voltage pulse with each tube drawing 40 A at full voltage. Efforts to stabilize these instabilities are presented along with some modeling and examination of the issues for gyrotron modulators.

  6. Feedback systems in the SLC

    SciTech Connect

    Thompson, K.A.; Jobe, R.K.; Johnson, R.; Phinney, N.

    1987-02-01

    Two classes of computer-controlled feedback have been implemented to stabilize parameters in subsystems of the SLC: (1) ''slow'' (time scales approx. minutes) feedback, and (2) ''fast'', i.e., pulse-to-pulse, feedback. The slow loops run in a single FEEDBACK process in the SLC host VAX, which acquires signals and sets control parameters via communication with the database and the network of normal SLC microprocessors. Slow loops exist to stabilize beam energy and energy spread, beam position and angle, and timing of kicker magnets, and to compensate for changes in the phase length of the rf drive line. The fast loops run in dedicated microprocessors, and may sample and/or feedback on particular parameters as often as every pulse of the SLC beam. The first implementations of fast feedback are to control transverse beam blow-up and to stabilize the energy and energy spread of bunches going into the SLC arcs. The overall architecture of the feedback software and the operator interface for controlling loops are discussed.

  7. Simple Optoelectronic Feedback in Microwave Oscillators

    NASA Technical Reports Server (NTRS)

    Maleki, Lute; Iltchenko, Vladimir

    2009-01-01

    A proposed method of stabilizing microwave and millimeter-wave oscillators calls for the use of feedback in optoelectronic delay lines characterized by high values of the resonance quality factor (Q). The method would extend the applicability of optoelectronic feedback beyond the previously reported class of optoelectronic oscillators that comprise two-port electronic amplifiers in closed loops with high-Q feedback circuits.

  8. Finite Feedback Cycling in Structural Equation Models

    ERIC Educational Resources Information Center

    Hayduk, Leslie A.

    2009-01-01

    In models containing reciprocal effects, or longer causal loops, the usual effect estimates assume that any effect touching a loop initiates an infinite cycling of effects around that loop. The real world, in contrast, might permit only finite feedback cycles. I use a simple hypothetical model to demonstrate that if the world permits only a few…

  9. Role of histone deacetylase 3 in ankylosing spondylitis via negative feedback loop with microRNA-130a and enhancement of tumor necrosis factor-1α expression in peripheral blood mononuclear cells

    PubMed Central

    JIANG, YA; WANG, LIN

    2016-01-01

    The present study was performed to investigate the molecular mechanism of ankylosing spondylitis (AS). The interaction between micro (mi)RNA-130a and its target tumor necrosis factor (TNF)-1α and histone deactylase (HDAC)3 was assessed in peripheral blood mononuclear cells (PBMCs) from AS patients. Increased HDAC3 and decreased miRNA-130a levels were observed in PBMCs from AS patients. HDAC3 knockdown or HDAC3 inhibition promoted the expression of miRNA-130a, and HDAC3 was recruited to the promoter region of the gene encoding miRNA-130a in PBMCs. In addition, miR-130a overexpression led to a decrease, whereas miR-130a inhibition led to an increase of TNF-1α expression in PBMCs. Furthermore, HDAC3 knockdown or HDAC3 inhibition was associated with simultaneous upregulation of the expression of miR-130a and downregulation of the expression of TNF-1α in PBMCs. These results indicated that HDAC3 was involved in the regulation of the underlying molecular mechanism of AS by forming a negative feedback loop with miR-130a and enhancement of TNF-1α expression. PMID:26531724

  10. miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR–p-PI3K/AKT-c-JUN

    PubMed Central

    Zhao, Mengyang; Luo, Rongcheng; Liu, Yiyi; Gao, Linyuan; Fu, Zhaojian; Fu, Qiaofen; Luo, Xiaojun; Chen, Yiyu; Deng, Xiaojie; Liang, Zixi; Li, Xin; Cheng, Chao; Liu, Zhen; Fang, Weiyi

    2016-01-01

    The biological role of miR-3188 has not yet been reported in the context of cancer. In this study, we observe that miR-3188 not only reduces cell-cycle transition and proliferation, but also significantly prolongs the survival time of tumour-bearing mice as well as sensitizes cells to 5-FU. Mechanistic analyses indicate that miR-3188 directly targets mTOR to inactivate p-PI3K/p-AKT/c-JUN and induces its own expression. This feedback loop further suppresses cell-cycle signalling through the p-PI3K/p-AKT/p-mTOR pathway. Interestingly, we also observe that miR-3188 direct targeting of mTOR is mediated by FOXO1 suppression of p-PI3K/p-AKT/c-JUN signalling. In clinical samples, reduced miR-3188 is an unfavourable factor and negatively correlates with mTOR and c-JUN levels but positively correlates with FOXO1 expression. Our studies demonstrate that as a tumour suppressor, miR-3188 directly targets mTOR to stimulate its own expression and participates in FOXO1-mediated repression of cell growth, tumorigenesis and NPC chemotherapy resistance. PMID:27095304

  11. API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-{kappa}B binding elements: Evidence for a positive feed-back loop pathway resulting in unremitting NF-{kappa}B activation

    SciTech Connect

    Hosokawa, Yoshitaka . E-mail: yhosokaw@aichi-cc.jp; Suzuki, Hiroko; Nakagawa, Masao; Lee, Tae H.; Seto, Masao

    2005-08-19

    t(11;18)(q21;q21) is a characteristic as well as the most frequent chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in a fusion transcript, API2-MALT1. Although API2-MALT1 has been shown to enforce activation of NF-{kappa}B signaling, the transcriptional target genes of this fusion protein remains to be identified. Our analyses of the API2-MALT transfectants suggested that one of the target genes may be the apoptotic inhibitor API2 gene. Luciferase reporter assays with deletion and mutational constructs of the API2 promoter and electrophoretic mobility shift assays established that API2-MALT1 induces transcriptional activation of the API2 gene through two NF-{kappa}B binding elements. Moreover, supershift experiments indicated that these elements are recognized by the NF-{kappa}B p50/p65 heterodimer. Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)-carrying MALT lymphomas, highlighting a positive feedback-loop pathway resulting in unremitting NF-{kappa}B activation.

  12. Strategies for effective feedback.

    PubMed

    Kritek, Patricia A

    2015-04-01

    Provision of regular feedback to trainees on clinical performance by supervising providers is increasingly recognized as an essential component of undergraduate and graduate health sciences education; however, many individuals have not been formally trained in this pedagogical skill. At the bedside or in the clinic, effective performance feedback can be accomplished by following four key steps. Begin by setting expectations that incorporate the trainee's personal goals and external objectives. Delineate how and when you will provide feedback to the learner. Next, directly observe the trainee's performance. This can be challenging while engaged on a busy clinical service, but a focus on discrete activities or interactions (e.g., family meeting, intravascular volume assessment using bedside ultrasound, or obtaining informed consent) is helpful. The third step is to plan and prioritize the feedback session. Feedback is most effective when given in a timely fashion and delivered in a safe environment. Limit the issues addressed because learners often disengage if confronted with too many deficiencies. Finally, when delivering feedback, begin by listening to the trainee's self-evaluation and then take a balanced approach. Describe in detail what the trainee does well and discuss opportunities for improvement with emphasis on specific, modifiable behaviors. The feedback loop is completed with a plan for follow-up reassessment. Through the use of these relatively simple practices, both the trainee and teacher can have a more productive learning experience. PMID:25723379

  13. The Anderson Current Loop

    NASA Technical Reports Server (NTRS)

    Anderson, Karl F.

    1994-01-01

    Four-wire-probe concept applied to electrical-resistance transducers. Anderson current loop is excitation-and-signal-conditioning circuit suitable for use with strain gauges, resistance thermometers, and other electrical-resistance transducers mounted in harsh environments. Used as alternative to Wheatstone bridge. Simplifies signal-conditioning problem, enabling precise measurement of small changes in resistance of transducer. Eliminates some uncertainties in Wheatstone-bridge resistance-change measurements in flight research. Current loop configuration makes effects of lead-wire and contact resistances insignificantly small. Also provides output voltage that varies linearly with change in gauge resistance, and does so at double sensitivity of Wheatstone bridge.

  14. Feedback sine wave driver design for ultrasonic transducers

    NASA Astrophysics Data System (ADS)

    Schweitzer, P.; Tisserand, E.; Hamed, A.; Andra, J.; Coutard, F.

    2009-07-01

    The optimal sinusoidal excitation of an ultrasonic transducer requests a knowledge of the frequency and the impedance of the used ceramic. These parameters, that vary during the application, depend on the characteristics of the transducer but also on the acoustic load of the propagation medium. In the search for an adaptive excitation, we propose the design of a digital generator assuring the functions of automatic tuning and impedance matching. The design uses the Butterworth-Van Dycke model of pizoelectric ceramics. The method of determination and identification of the model parameters is presented and applied on three different transducers. The negative feedback of the generator is carried out by the signal measured on the transducers. The dynamic voltage being very variable, the output resistor of the driver is controlled by transducer impedance. This feedback control allows the stability of the output voltage to a constant value whatever the frequency and the medium is. A Simulink^circledR model of the regulation loop shows that the frequency tuning could be realized by exploiting the command signal of the driver resistance. The precision and the stability of the feedback system are tested for frequencies between 1 to 3 MHz.

  15. Digital phase-lock loop

    NASA Technical Reports Server (NTRS)

    Thomas, Jr., Jess B. (Inventor)

    1991-01-01

    An improved digital phase lock loop incorporates several distinctive features that attain better performance at high loop gain and better phase accuracy. These features include: phase feedback to a number-controlled oscillator in addition to phase rate; analytical tracking of phase (both integer and fractional cycles); an amplitude-insensitive phase extractor; a more accurate method for extracting measured phase; a method for changing loop gain during a track without loss of lock; and a method for avoiding loss of sampled data during computation delay, while maintaining excellent tracking performance. The advantages of using phase and phase-rate feedback are demonstrated by comparing performance with that of rate-only feedback. Extraction of phase by the method of modeling provides accurate phase measurements even when the number-controlled oscillator phase is discontinuously updated.

  16. Generalized fast feedback system in the SLC

    SciTech Connect

    Hendrickson, L.; Allison, S.; Gromme, T.; Himel, T.; Krauter, K.; Rouse, F.; Sass, R.; Shoaee, H.

    1991-11-01

    A generalized fast feedback system has been developed to stabilize beams at various locations in the SLC. The system is designed to perform measurements and change actuator settings to control beam states such as position, angle and energy on a pulse to pulse basis. The software design is based on the state space formalism of digital control theory. The system is database-driven, facilitating the addition of new loops without requiring additional software. A communications system, KISNet, provides fast communications links between microprocessors for feedback loops which involve multiple micros. Feedback loops have been installed in seventeen locations throughout the SLC and have proven to be invaluable in stabilizing the machine.

  17. Interactive Information Seeking and Retrieving: A Third Feedback Framework.

    ERIC Educational Resources Information Center

    Spink, Amanda

    1996-01-01

    Presents an overview of feedback within the cybernetics and social frameworks. These feedback concepts are then compared with the interactive feedback concept evolving within the framework of information seeking and retrieving, based on their conceptualization of the feedback loop and notion of information. (Author/AEF)

  18. Solid state high-voltage pulser operates with low supply voltage

    NASA Technical Reports Server (NTRS)

    Milberger, W. E.

    1968-01-01

    High speed klystron cathode pulser requires low voltage to generate high-voltage pulses. Broadband video transformers are wound in two configurations - /1/ transmission line, multifilar toroids and /2/ loop coupling toroids. The circuit adapts to generate high-speed, high-voltage, high-stability power pulses at megawatt levels.

  19. cPLA(2)α gene activation by IL-1β is dependent on an upstream kinase pathway, enzymatic activation and downstream 15-lipoxygenase activity: a positive feedback loop.

    PubMed

    Walters, Jewell N; Bickford, Justin S; Beachy, Dawn E; Newsom, Kimberly J; Herlihy, John-David H; Peck, Molly V; Qiu, Xiaolei; Nick, Harry S

    2011-12-01

    Cytosolic phospholipase A(2)α (cPLA(2)α) is the most widely studied member of the Group IV PLA(2) family. The enzyme is Ca(2+)-dependent with specificity for phospholipid substrates containing arachidonic acid. As the pinnacle of the arachidonic acid pathway, cPLA(2)α has a primary role in the biosynthesis of a diverse family of eicosanoid metabolites, with potent physiological, inflammatory and pathological consequences. cPLA(2)α activity is regulated by pro-inflammatory stimuli through pathways involving increased intracellular Ca(2+) levels, phosphorylation coupled to increased enzymatic activity and de novo gene transcription. This study addresses the signal transduction pathways for protein phosphorylation and gene induction following IL-1β stimulation in human fetal lung fibroblasts. Our results utilizing both inhibitors and kinase-deficient cells demonstrate that cPLA(2)α is phosphorylated within 10min of IL-1β treatment, an event requiring p38 MAPK as well as the upstream kinase, MKK3/MKK6. Inhibition of p38 MAPK also blocks the phosphorylation of a downstream, nuclear kinase, MSK-1. Our results further demonstrate that the activities of both cPLA(2)α and a downstream lipoxygenase (15-LOX2) are required for IL-1β-dependent induction of cPLA(2)α mRNA expression. Overall, these data support an MKK3/MKK6→p38 MAPK→MSK-1→cPLA(2)α→15-LOX2-dependent, positive feedback loop where a protein's enzymatic activity is required to regulate its own gene induction by a pro-inflammatory stimulus. PMID:21771656

  20. A double feedback loop mediated by microRNA-23a/27a/24-2 regulates M1 versus M2 macrophage polarization and thus regulates cancer progression.

    PubMed

    Ma, Sisi; Liu, Min; Xu, Zhenbiao; Li, Yanshuang; Guo, Hui; Ge, Yehua; Liu, Yanxin; Zheng, Dexian; Shi, Juan

    2016-03-22

    In response to microenvironmental signals, macrophages undergo different types of activation, including the "classic" pro-inflammatory phenotype (also called M1) and the "alternative" anti-inflammatory phenotype (also called M2). Macrophage polarized activation has profound effects on immune and inflammatory responses, but mechanisms underlying the various types of macrophage is still in its infancy. In this study, we reported that M1-type stimulation could down-regulate miR-23a/27a/24-2 cluster transcription through the binding of NF-κB to this cluster's promoter and that miR-23a in turn activated the NF-κB pathway by targeting A20 and thus promoted the production of pro-inflammatory cytokines. Furthermore, STAT6 occupied the miR-23a/27a/24-2 cluster promoter and activated their transcription in IL-4-stimulated macrophages. In addition, miR-23a in turn suppressed the JAK1/STAT-6 pathway and reduced the production of M2 type cytokines by targeting JAK1 and STAT-6 directly, while miR-27a showed the same phenotype by targeting IRF4 and PPAR-γ. The miR-23a/27a/24-2 cluster was shown to be significantly decreased in TAMs of breast cancer patients, and macrophages overexpressing the miR-23a/27a/24-2 cluster inhibited tumor growth in vivo. Taken together, these data integrated microRNA expression and function into macrophage polarization networks and identified a double feedback loop consisting of the miR-23a/27a/24-2 cluster and the key regulators of the M1 and M2 macrophage polarization pathway. Moreover, miR-23a/27a/24-2 regulates the polarization of tumor-associated macrophages and thus promotes cancer progression. PMID:26540574

  1. A positive feedback loop of IL-21 signaling provoked by homeostatic CD4+CD25- T cell expansion is essential for the development of arthritis in autoimmune K/BxN mice.

    PubMed

    Jang, Eunkyeong; Cho, Sin-Hye; Park, Hyunjoo; Paik, Doo-Jin; Kim, Jung Mogg; Youn, Jeehee

    2009-04-15

    Rheumatoid arthritis is a joint-specific autoimmune inflammatory disease of unknown etiology. The K/BxN mouse is a model of rheumatoid arthritis that is thought to be mainly due to autoantibody-mediated inflammatory responses. We showed previously that homeostatic proliferation of autoreactive CD4(+) T cells is required for disease initiation in the K/BxN mice. In this study, we show that the homeostatically proliferating CD4(+)CD25(-) T cells produce IL-21. We generated IL-21R-deficient (IL-21R(-/-)) K/BxN mice and found that these mice were completely refractory to the development of spontaneous arthritis. They contained fewer CD4(+) T cells with a reduced proportion of homeostatically proliferating cells, fewer follicular Th cells, and, surprisingly, more Th17 cells than their control counterparts. They also failed to develop IgG1(+) memory B cells and autoantigen-specific IgG1 Ab-secreting cells. IL-21 induced expression of receptor activator of NF-kappaB ligand (RANKL) a regulator of osteoclastogenesis, and few RANKL-expressing infiltrates were found in the synovia of IL-21R(-/-) K/BxN mice. Thus, our results demonstrate that IL-21 forms a positive feedback autocrine loop involving homeostatically activated CD4(+) cells and that it plays an essential role in the development of autoimmune arthritis by mechanisms dependent on follicular Th cell development, autoreactive B cell maturation, and RANKL induction but independent of Th17 cell function. Consistent with this, in vivo administration of soluble the IL-21R-Fc fusion protein delayed the onset and progression of arthritis. Our findings suggest that effective targeting of IL-21-mediated processes may be useful in treating autoimmune arthritis. PMID:19342640

  2. A Positive Feedback Loop between HEAT SHOCK PROTEIN101 and HEAT STRESS-ASSOCIATED 32-KD PROTEIN Modulates Long-Term Acquired Thermotolerance Illustrating Diverse Heat Stress Responses in Rice Varieties1[W][OPEN

    PubMed Central

    Lin, Meng-yi; Chai, Kuo-hsing; Ko, Swee-suak; Kuang, Lin-yun; Lur, Huu-Sheng; Charng, Yee-yung

    2014-01-01

    Heat stress is an important factor that has a negative impact on rice (Oryza sativa) production. To alleviate this problem, it is necessary to extensively understand the genetic basis of heat tolerance and adaptability to heat stress in rice. Here, we report the molecular mechanism underlying heat acclimation memory that confers long-term acquired thermotolerance (LAT) in this monocot plant. Our results showed that a positive feedback loop formed by two heat-inducible genes, HEAT SHOCK PROTEIN101 (HSP101) and HEAT STRESS-ASSOCIATED 32-KD PROTEIN (HSA32), at the posttranscriptional level prolongs the effect of heat acclimation in rice seedlings. The interplay between HSP101 and HSA32 also affects basal thermotolerance of rice seeds. These findings are similar to those reported for the dicot plant Arabidopsis (Arabidopsis thaliana), suggesting a conserved function in plant heat stress response. Comparison between two rice cultivars, japonica Nipponbare and indica N22 showed opposite performance in basal thermotolerance and LAT assays. ‘N22’ seedlings have a higher basal thermotolerance level than cv Nipponbare and vice versa at the LAT level, indicating that these two types of thermotolerance can be decoupled. The HSP101 and HSA32 protein levels were substantially higher in cv Nipponbare than in cv N22 after a long recovery following heat acclimation treatment, at least partly explaining the difference in the LAT phenotype. Our results point out the complexity of thermotolerance diversity in rice cultivars, which may need to be taken into consideration when breeding for heat tolerance for different climate scenarios. PMID:24520156

  3. VOLTAGE REGULATOR

    DOEpatents

    Von Eschen, R.L.; Scheele, P.F.

    1962-04-24

    A transistorized voltage regulator which provides very close voitage regulation up to about 180 deg F is described. A diode in the positive line provides a constant voltage drop from the input to a regulating transistor emitter. An amplifier is coupled to the positive line through a resistor and is connected between a difference circuit and the regulating transistor base which is negative due to the difference in voltage drop across thc diode and the resistor so that a change in the regulator output causes the amplifier to increase or decrease the base voltage and current and incrcase or decrease the transistor impedance to return the regulator output to normal. (AEC)

  4. Modular high voltage power supply for chemical analysis

    DOEpatents

    Stamps, James F.; Yee, Daniel D.

    2007-01-09

    A high voltage power supply for use in a system such as a microfluidics system, uses a DC--DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC--DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

  5. Modular high voltage power supply for chemical analysis

    DOEpatents

    Stamps, James F.; Yee, Daniel D.

    2008-07-15

    A high voltage power supply for use in a system such as a microfluidics system, uses a DC-DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC-DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

  6. Modular high voltage power supply for chemical analysis

    DOEpatents

    Stamps, James F.; Yee, Daniel D.

    2010-05-04

    A high voltage power supply for use in a system such as a microfluidics system, uses a DC-DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC-DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

  7. TUNE FEEDBACK AT RHIC

    SciTech Connect

    CAMERON,P.; CERNIGLIA,P.; CONNOLLY,R.; CUPOLO,J.; DAWSON,W.C.; DEGEN,C.; DELLAPENNA,A.; DELONG,J.; DREES,A.; HUHN,A.; KESSELMAN,M.; MARUSIC,A.; OERTER,B.; MEAD,J.; SCHULTHEISS,C.; SIKORA,R.; VAN ZEIJTS,J.

    2001-06-18

    Preliminary phase-locked loop betatron tune measurement results were obtained during RHIC 2000 with a resonant Beam Position Monitor. These results suggested the possibility of incorporating PLL tune measurement into a tune feedback system for RHIC 2001. Tune feedback is useful in a superconducting accelerator, where the machine cycle time is long and inefficient acceleration due to resonance crossing is not comfortably tolerated. This is particularly true with the higher beam intensities planned for RHIC 2001. We present descriptions of a PLL tune measurement system implemented in the DSP/FPGA environment of a RHIC BPM electronics module and the feedback system into which the measurement is incorporated to regulate tune. In addition, we present results from the commissioning of this system during RHIC 2001.

  8. Design and Construction of Low Cost High Voltage dc Power Supply for Constant Power Operation

    NASA Astrophysics Data System (ADS)

    Kumar, N. S.; Jayasankar, V.

    2013-06-01

    Pulsed load applications like laser based systems need high voltage dc power supplies with better regulation characteristics. This paper presents the design, construction and testing of dc power supply with 1 kV output at 300 W power level. The designed converter has half bridge switched mode power supply (SMPS) configuration with 20 kHz switching. The paper covers the design of half bridge inverter, closed loop control, High frequency transformer and other related electronics. The designed power supply incorporates a low cost OPAMP based feedback controller which is designed using small signal modelling of the converter. The designed converter was constructed and found to work satisfactorily as per the specifications.

  9. Power-MOSFET Voltage Regulator

    NASA Technical Reports Server (NTRS)

    Miller, W. N.; Gray, O. E.

    1982-01-01

    Ninety-six parallel MOSFET devices with two-stage feedback circuit form a high-current dc voltage regulator that also acts as fully-on solid-state switch when fuel-cell out-put falls below regulated voltage. Ripple voltage is less than 20 mV, transient recovery time is less than 50 ms. Parallel MOSFET's act as high-current dc regulator and switch. Regulator can be used wherever large direct currents must be controlled. Can be applied to inverters, industrial furnaces photovoltaic solar generators, dc motors, and electric autos.

  10. STABILIZED FEEDBACK AMPLIFIER

    DOEpatents

    Fishbine, H.L.; Sewell, C. Jr.

    1957-08-01

    Negative feedback amplifiers, and particularly a negative feedback circuit which is economical on amode power consumption, are described. Basically, the disclosed circuit comprises two tetrode tubes where the output of the first tube is capacitamce coupled to the grid of the second tube, which in turn has its plate coupled to the cathode of the first tube to form a degenerative feedback circuit. Operating potential for screen of the second tube is supplied by connecting the cathode resistor of the first tube to the screen, while the screen is by-passed to the cathode of its tube for the amplified frequencies. Also, the amplifier incorporates a circuit to stabilize the transconductance of the tubes by making the grid potential of each tube interdependent on anode currents of both lubes by voltage divider circuitry.

  11. Computer automation for feedback system design

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Mathematical techniques and explanations of various steps used by an automated computer program to design feedback systems are summarized. Special attention was given to refining the automatic evaluation suboptimal loop transmission and the translation of time to frequency domain specifications.

  12. Phase loop bandwidth measurements on the advanced photon source 352 MHz rf systems

    SciTech Connect

    Horan, D.; Nassiri, A.; Schwartz, C.

    1997-08-01

    Phase loop bandwidth tests were performed on the Advanced Photon Source storage ring 352-MHz rf systems. These measurements were made using the HP3563A Control Systems Analyzer, with the rf systems running at 30 kilowatts into each of the storage ring cavities, without stored beam. An electronic phase shifter was used to inject approximately 14 degrees of stimulated phase shift into the low-level rf system, which produced measureable response voltage in the feedback loops without upsetting normal rf system operation. With the PID (proportional-integral-differential) amplifier settings at the values used during accelerator operation, the measurement data revealed that the 3-dB response for the cavity sum and klystron power-phase loops is approximately 7 kHz and 45 kHz, respectively, with the cavities the primary bandwidth-limiting factor in the cavity-sum loop. Data were taken at various PID settings until the loops became unstable. Crosstalk between the two phase loops was measured.

  13. Pulsed feedback defers cellular differentiation.

    PubMed

    Levine, Joe H; Fontes, Michelle E; Dworkin, Jonathan; Elowitz, Michael B

    2012-01-01

    Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable "polyphasic" positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a "timer" that operates over timescales much longer than a cell cycle. PMID:22303282

  14. Pepper CabZIP63 acts as a positive regulator during Ralstonia solanacearum or high temperature-high humidity challenge in a positive feedback loop with CaWRKY40.

    PubMed

    Shen, Lei; Liu, Zhiqin; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Lin, Wei; Wang, Rongzhang; Yu, Huanxin; Mou, Shaoliang; Hussain, Ansar; Cheng, Wei; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-04-01

    CaWRKY40 is known to act as a positive regulator in the response of pepper (Capsicum annuum) toRalstonia solanacearuminoculation (RSI) or high temperature-high humidity (HTHH), but the underlying mechanism remains elusive. Herein, we report that CabZIP63, a pepper bZIP family member, participates in this process by regulating the expression ofCaWRKY40 CabZIP63 was found to localize in the nuclei, be up-regulated by RSI or HTHH, bind to promoters of bothCabZIP63(pCabZIP63) andCaWRKY40(pCaWRKY40), and activatepCabZIP63- andpCaWRKY40-driven β-glucuronidase expression in a C- or G-box-dependent manner. Silencing ofCabZIP63by virus-induced gene silencing (VIGS) in pepper plants significantly attenuated their resistance to RSI and tolerance to HTHH, accompanied by down-regulation of immunity- or thermotolerance-associatedCaPR1,CaNPR1,CaDEF1, andCaHSP24 Hypersensitive response-mediated cell death and expression of the tested immunity- and thermotolerance-associated marker genes were induced by transient overexpression (TOE) ofCabZIP63, but decreased by that ofCabZIP63-SRDX Additionally, binding of CabZIP63 topCaWRKY40was up-regulated by RSI or HTHH, and the transcript level ofCaWRKY40and binding of CaWRKY40 to the promoters ofCaPR1,CaNPR1,CaDEF1andCaHSP24were up-regulated by TOE ofCabZIP63.On the other hand,CabZIP63was also up-regulated transcriptionally by TOE ofCaWRKY40 The data suggest collectively that CabZIP63 directly or indirectly regulates the expression ofCaWRKY40at both the transcriptional and post-transcriptional level, forming a positive feedback loop with CaWRKY40 during pepper's response to RSI or HTHH. Altogether, our data will help to elucidate the underlying mechanism of crosstalk between pepper's response to RSI and HTHH. PMID:26936828

  15. Activation of an early feedback survival loop involving phospho-ErbB3 is a general response of melanoma cells to RAF/MEK inhibition and is abrogated by anti-ErbB3 antibodies

    PubMed Central

    2013-01-01

    Background Treatment of advanced melanoma has been improved with the advent of the BRAF inhibitors. However, a limitation to such treatment is the occurrence of resistance. Several mechanisms have been identified to be responsible for the development of resistance, either MEK-dependent or MEK-independent. In order to overcome resistance due to reactivation of MEK signaling, MEK inhibitors are being clinically developed with promising results. However, also in this case resistance inevitably occurs. It has been recently reported that ErbB3, a member of the EGFR receptor family, may be involved in the establishment of drug resistance. Methods Three melanoma cell lines were tested: LOX IMVI (BRAF V600E), MST-L (BRAF V600R) and WM266 (BRAF V600D). Phosphorylation of Receptor Tyrosine Kinases (RTKs) was assessed by an RTK array. Western blot analysis was performed on total protein extracts using anti-ErbB3, anti-AKT and anti-ERK 1/2 antibodies. The expression of neuregulin after vemurafenib treatment was assessed by Real Time PCR and Western blotting. The growth inhibitory effects of vemurafenib, GSK1120212b and/or anti-ErbB3 mAbs were evaluated by in vitro colony formation assays. Results In the present study we demonstrate that ErbB3 is the main RTK undergoing rapidly hyperphosphorylation upon either treatment with a BRAF inhibitor or with a MEK inhibitor in a panel of melanoma cell lines harboring a variety of V600BRAF mutations and that this results in a strong activation of phospho-AKT. Importantly, ErbB3 activation is fully abrogated by the simultaneous use of anti-ErbB3 monoclonal antibodies, which are also shown to potently synergize with BRAF inhibitors in the inactivation of both AKT and ERK pathways and in the inhibition of melanoma cell growth. We show that upregulation of phospho-ErbB3 is due to an autocrine loop involving increased transcription and production of neuregulin by melanoma cells. Conclusions On the basis of these results, we propose that initial co-treatment with BRAF and/or MEK inhibitors and anti-ErbB3 antibodies should be pursued as a strategy to reduce the ErbB3-dependent feedback survival mechanism and enhance duration of clinical response. PMID:23890105

  16. Pepper CabZIP63 acts as a positive regulator during Ralstonia solanacearum or high temperature–high humidity challenge in a positive feedback loop with CaWRKY40

    PubMed Central

    Shen, Lei; Liu, Zhiqin; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Lin, Wei; Wang, Rongzhang; Yu, Huanxin; Mou, Shaoliang; Hussain, Ansar; Cheng, Wei; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-01-01

    CaWRKY40 is known to act as a positive regulator in the response of pepper (Capsicum annuum) to Ralstonia solanacearum inoculation (RSI) or high temperature–high humidity (HTHH), but the underlying mechanism remains elusive. Herein, we report that CabZIP63, a pepper bZIP family member, participates in this process by regulating the expression of CaWRKY40. CabZIP63 was found to localize in the nuclei, be up-regulated by RSI or HTHH, bind to promoters of both CabZIP63 (pCabZIP63) and CaWRKY40 (pCaWRKY40), and activate pCabZIP63- and pCaWRKY40-driven β-glucuronidase expression in a C- or G-box-dependent manner. Silencing of CabZIP63 by virus-induced gene silencing (VIGS) in pepper plants significantly attenuated their resistance to RSI and tolerance to HTHH, accompanied by down-regulation of immunity- or thermotolerance-associated CaPR1, CaNPR1, CaDEF1, and CaHSP24. Hypersensitive response-mediated cell death and expression of the tested immunity- and thermotolerance-associated marker genes were induced by transient overexpression (TOE) of CabZIP63, but decreased by that of CabZIP63-SRDX. Additionally, binding of CabZIP63 to pCaWRKY40 was up-regulated by RSI or HTHH, and the transcript level of CaWRKY40 and binding of CaWRKY40 to the promoters of CaPR1, CaNPR1, CaDEF1 and CaHSP24 were up-regulated by TOE of CabZIP63. On the other hand, CabZIP63 was also up-regulated transcriptionally by TOE of CaWRKY40. The data suggest collectively that CabZIP63 directly or indirectly regulates the expression of CaWRKY40 at both the transcriptional and post-transcriptional level, forming a positive feedback loop with CaWRKY40 during pepper’s response to RSI or HTHH. Altogether, our data will help to elucidate the underlying mechanism of crosstalk between pepper’s response to RSI and HTHH. PMID:26936828

  17. Research on output feedback control

    NASA Technical Reports Server (NTRS)

    Calise, Anthony J.

    1988-01-01

    A summary is presented of the main results obtained during the course of research on output feedback control. The term output feedback is used to denote a controller design approach which does not rely on an observer to estimate the states of the system. Thus, the order of the controller is fixed, and can even be zero order, which amounts to constant gain ouput feedback. The emphasis has been on optimal output feedback. That is, a fixed order controller is designed based on minimizing a suitably chosen quadratic performance index. A number of problem areas that arise in this context have been addressed. These include developing suitable methods for selecting an index of performance, both time domain and frequency domain methods for achieving robustness of the closed loop system, developing canonical forms to achieve a minimal parameterization for the controller, two time scale design formulations for ill-conditioned systems, and the development of convergent numerical algorithms for solving the output feedback problem.

  18. Oscillations in nonlinear feedback systems.

    NASA Technical Reports Server (NTRS)

    Williamson, D.

    1973-01-01

    It is shown how some basic ideas from system theory and differential geometry can be used to establish new results concerning the existance of oscillations for autonomous feedback systems. The conditions obtained are expressed in terms of the frequency response characteristic of the open-loop system and certain general properties of the nonlinearity.

  19. A Critical Quantity for Noise Attenuation in Feedback Systems

    PubMed Central

    Wang, Liming; Xin, Jack; Nie, Qing

    2010-01-01

    Feedback modules, which appear ubiquitously in biological regulations, are often subject to disturbances from the input, leading to fluctuations in the output. Thus, the question becomes how a feedback system can produce a faithful response with a noisy input. We employed multiple time scale analysis, Fluctuation Dissipation Theorem, linear stability, and numerical simulations to investigate a module with one positive feedback loop driven by an external stimulus, and we obtained a critical quantity in noise attenuation, termed as “signed activation time”. We then studied the signed activation time for a system of two positive feedback loops, a system of one positive feedback loop and one negative feedback loop, and six other existing biological models consisting of multiple components along with positive and negative feedback loops. An inverse relationship is found between the noise amplification rate and the signed activation time, defined as the difference between the deactivation and activation time scales of the noise-free system, normalized by the frequency of noises presented in the input. Thus, the combination of fast activation and slow deactivation provides the best noise attenuation, and it can be attained in a single positive feedback loop system. An additional positive feedback loop often leads to a marked decrease in activation time, decrease or slight increase of deactivation time and allows larger kinetic rate variations for slow deactivation and fast activation. On the other hand, a negative feedback loop may increase the activation and deactivation times. The negative relationship between the noise amplification rate and the signed activation time also holds for the six other biological models with multiple components and feedback loops. This principle may be applicable to other feedback systems. PMID:20442870

  20. Architecture for a High-to-Medium-Voltage Power Converter

    NASA Technical Reports Server (NTRS)

    Vorpenian, Vatche

    2008-01-01

    A power converter now undergoing development is required to operate at a DC input potential ranging between 5.5 and 10 kV and a DC output potential of 400 V at a current up to 25 A. This power converter is also required to be sufficiently compact and reliable to fit and operate within the confines of a high-pressure case to be lowered to several miles (approx.5 km) below the surface of the ocean. The architecture chosen to satisfy these requirements calls for a series/ parallel arrangement of 48 high-frequency, pulse-width-modulation (PWM), transformer-isolation DC-to-DC power converter blocks. The input sides of the converter blocks would be connected in series so that the input potential would be divided among them, each of them being exposed to an input potential of no more than 10 kV/48 . 210 V. The series connection of inputs would also enforce a requirement that all the converter blocks operate at the same input current. The outputs of the converter blocks would be connected in a matrix comprising 6 parallel legs, each leg being a cascade of eight outputs wired in series (see figure). All the converter blocks would be identical within the tolerances of the values of their components. A single voltage feedback loop would regulate the output potential. All the converter blocks would be driven by the same PWM waveform generated by this feedback loop. The power transformer of each converter block would have a unity turns ratio and would be capable of withstanding as much as 10 kVDC between its primary and secondary windings. (Although, in general, the turns ratio could be different from unity, the simplest construction for minimizing leakage and maximizing breakdown voltage is attained at a turns ratio of unity.)

  1. Self-organization of pulsing and bursting in a CO2 laser with opto-electronic feedback

    NASA Astrophysics Data System (ADS)

    Freire, Joana G.; Meucci, Riccardo; Arecchi, Fortunato Tito; Gallas, Jason A. C.

    2015-09-01

    We report a detailed investigation of the stability of a CO2 laser with feedback as described by a six-dimensional rate-equations model which provides satisfactory agreement between numerical and experimental results. We focus on experimentally accessible parameters, like bias voltage, feedback gain, and the bandwidth of the feedback loop. The impact of decay rates and parameters controlling cavity losses are also investigated as well as control planes which imply changes of the laser physical medium. For several parameter combinations, we report stability diagrams detailing how laser spiking and bursting is organized over extended intervals. Laser pulsations are shown to emerge organized in several hitherto unseen regular and irregular phases and to exhibit a much richer and complex range of behaviors than described thus far. A significant observation is that qualitatively similar organization of laser spiking and bursting can be obtained by tuning rather distinct control parameters, suggesting the existence of unexpected symmetries in the laser control space.

  2. Self-organization of pulsing and bursting in a CO{sub 2} laser with opto-electronic feedback

    SciTech Connect

    Freire, Joana G.; Meucci, Riccardo; Arecchi, Fortunato Tito; and others

    2015-09-15

    We report a detailed investigation of the stability of a CO{sub 2} laser with feedback as described by a six-dimensional rate-equations model which provides satisfactory agreement between numerical and experimental results. We focus on experimentally accessible parameters, like bias voltage, feedback gain, and the bandwidth of the feedback loop. The impact of decay rates and parameters controlling cavity losses are also investigated as well as control planes which imply changes of the laser physical medium. For several parameter combinations, we report stability diagrams detailing how laser spiking and bursting is organized over extended intervals. Laser pulsations are shown to emerge organized in several hitherto unseen regular and irregular phases and to exhibit a much richer and complex range of behaviors than described thus far. A significant observation is that qualitatively similar organization of laser spiking and bursting can be obtained by tuning rather distinct control parameters, suggesting the existence of unexpected symmetries in the laser control space.

  3. High-voltage circuits for power management on 65 nm CMOS

    NASA Astrophysics Data System (ADS)

    Pashmineh, S.; Killat, D.

    2015-11-01

    This paper presents two high-voltage circuits used in power management, a switching driver for buck converter with optimized on-resistance and a low dropout (LDO) voltage regulator with 2-stacked pMOS pass devices. The circuit design is based on stacked MOSFETs, thus the circuits are technology independent. High-voltage drivers with stacked devices suffer from slow switching characteristics. In this paper, a new concept to adjust gate voltages of stacked transistors is introduced for reduction of on-resistance. According to the theory, a circuit is proposed that drives 2 stacked transistors of a driver. Simulation results show a reduction of the on-resistance between 27 and 86 % and a reduction of rise and fall times between 16 and 83 % with a load capacitance of 150 pF at various supply voltages, compared to previous work. The concept can be applied to each high-voltage driver that is based on a number (N) of stacked transistors. The high voltage compatibility of the low drop-out voltage regulator (LDO) is established by a 2-stacked pMOS transistors as pass device controlled by two regulators: an error amplifier and a 2nd amplifier adjusting the division of the voltages between the two pass transistors. A high GBW and good DC accuracy in line and load regulation is achieved by using 3-stage error amplifiers. To improve stability, two feedback loops are utilized. In this paper, the 2.5 V I/O transistors of the TSMC 65 nm CMOS technology are used for the circuit design.

  4. Feedback Regulation and Its Efficiency in Biochemical Networks

    NASA Astrophysics Data System (ADS)

    Kobayashi, Tetsuya J.; Yokota, Ryo; Aihara, Kazuyuki

    2016-01-01

    Intracellular biochemical networks fluctuate dynamically due to various internal and external sources of fluctuation. Dissecting the fluctuation into biologically relevant components is important for understanding how a cell controls and harnesses noise and how information is transferred over apparently noisy intracellular networks. While substantial theoretical and experimental advancement on the decomposition of fluctuation was achieved for feedforward networks without any loop, we still lack a theoretical basis that can consistently extend such advancement to feedback networks. The main obstacle that hampers is the circulative propagation of fluctuation by feedback loops. In order to define the relevant quantity for the impact of feedback loops for fluctuation, disentanglement of the causally interlocked influences between the components is required. In addition, we also lack an approach that enables us to infer non-perturbatively the influence of the feedback to fluctuation in the same way as the dual reporter system does in the feedforward networks. In this work, we address these problems by extending the work on the fluctuation decomposition and the dual reporter system. For a single-loop feedback network with two components, we define feedback loop gain as the feedback efficiency that is consistent with the fluctuation decomposition for feedforward networks. Then, we clarify the relation of the feedback efficiency with the fluctuation propagation in an open-looped FF network. Finally, by extending the dual reporter system, we propose a conjugate feedback and feedforward system for estimating the feedback efficiency non-perturbatively only from the statistics of the system.

  5. Feedback Regulation and Its Efficiency in Biochemical Networks

    NASA Astrophysics Data System (ADS)

    Kobayashi, Tetsuya J.; Yokota, Ryo; Aihara, Kazuyuki

    2016-03-01

    Intracellular biochemical networks fluctuate dynamically due to various internal and external sources of fluctuation. Dissecting the fluctuation into biologically relevant components is important for understanding how a cell controls and harnesses noise and how information is transferred over apparently noisy intracellular networks. While substantial theoretical and experimental advancement on the decomposition of fluctuation was achieved for feedforward networks without any loop, we still lack a theoretical basis that can consistently extend such advancement to feedback networks. The main obstacle that hampers is the circulative propagation of fluctuation by feedback loops. In order to define the relevant quantity for the impact of feedback loops for fluctuation, disentanglement of the causally interlocked influences between the components is required. In addition, we also lack an approach that enables us to infer non-perturbatively the influence of the feedback to fluctuation in the same way as the dual reporter system does in the feedforward networks. In this work, we address these problems by extending the work on the fluctuation decomposition and the dual reporter system. For a single-loop feedback network with two components, we define feedback loop gain as the feedback efficiency that is consistent with the fluctuation decomposition for feedforward networks. Then, we clarify the relation of the feedback efficiency with the fluctuation propagation in an open-looped FF network. Finally, by extending the dual reporter system, we propose a conjugate feedback and feedforward system for estimating the feedback efficiency non-perturbatively only from the statistics of the system.

  6. Balanced-Bridge Feedback Control Of Motor

    NASA Technical Reports Server (NTRS)

    Lurie, Boris J.

    1990-01-01

    Sensitivity to variations in electrical and mechanical characteristics reduced. Proposed control system for motor-driven rotary actuator includes three nested feedback loops which, when properly designed, decoupled from each other. Intended to increase accuracy of control by mitigating such degrading effects as vibrations and variations in electrical and mechanical characteristics of structure rotated. Lends itself to optimization of performance via independent optimization of each of three loops. Includes outer, actuator, and driver feedback loops, configured so that actuator is subsystem, and driver is subsystem of actuator.

  7. Studies Of Positive-Position-Feedback Control

    NASA Technical Reports Server (NTRS)

    Fanson, James L.; Caughey, Thomas K.

    1992-01-01

    Report discusses theoretical and experimental studies of positive-position-feedback control for suppressing vibrations in large flexible structures. Positive-position-feedback control involves placement of actuators and sensors on structure; control voltages applied to actuators in response to outputs of sensors processed via compensator algorithm. Experiments demonstrate feasibility of suppressing vibrations by positive position feedback, and spillover of vibrational energy into uncontrolled modes has stabilizing effect if control gain sufficiently small.

  8. Predictive feedback control.

    PubMed

    Giovanini, Leonardo L

    2003-04-01

    In this work a new method for designing predictive controllers for linear single-input/single-output systems is presented. It uses only one prediction of the process output J time intervals ahead to compute the correspondent future error. Then, the predictive feedback controller is defined by introducing a filter which weights the last w predicted errors. In this way, the resulting control action is computed by observing the system future behavior and also by weighting present and past errors. This last feature improves the closed-loop performance to disturbance rejection as shown through simulations of two linear systems and a nonlinear continuous stirred tank reactor. PMID:12708540

  9. Feedback Configuration Tools for LHC Low Level RF

    SciTech Connect

    Van Winkle, D.; Fox, J.; Mastorides, T.; Rivetta, C.; Baudrenghien, P.; Butterworth, A.; Molendijk, J.; /CERN

    2009-12-16

    The LHC Low Level RF System (LLRF) is a complex multi-VME crate system which is used to regulate the superconductive cavity gap voltage as well as to lower the impedance as seen by the beam through low latency feedback. This system contains multiple loops with several parameters to be set before the loops can be closed. In this paper, we present a suite of MATLAB based tools developed to perform the preliminary alignment of the RF stations and the beginnings of a closed loop model based alignment routine. We briefly introduce the RF system and in particular the base band (time domain noise based) network analyzer system built into the LHC LLRF. The main focus of this paper is the methodology of the algorithms used by the routines within the context of the overall system. Measured results are presented that validate the technique. Because the RF systems are located in a cavern 120 m underground in a location which is relatively un-accessible without beam and completely un-accessible with beam present or magnets are energized, these remotely operated tools are a necessity for the CERN LLRF team to maintain and tune their LLRF systems in a similar fashion as to what was done very successfully in PEP-II at SLAC.

  10. A Novel Digital Closed Loop MEMS Accelerometer Utilizing a Charge Pump

    PubMed Central

    Chu, Yixing; Dong, Jingxin; Chi, Baoyong; Liu, Yunfeng

    2016-01-01

    This paper presents a novel digital closed loop microelectromechanical system (MEMS) accelerometer with the architecture and experimental evaluation. The complicated timing diagram or complex power supply in published articles are circumvented by using a charge pump system of adjustable output voltage fabricated in a 2P4M 0.35 µm complementary metal-oxide semiconductor (CMOS) process, therefore making it possible for interface circuits of MEMS accelerometers to be integrated on a single die on a large scale. The output bitstream of the sigma delta modulator is boosted by the charge pump system and then applied on the feedback comb fingers to form electrostatic forces so that the MEMS accelerometer can operate in a closed loop state. Test results agree with the theoretical formula nicely. The nonlinearity of the accelerometer within ±1 g is 0.222% and the long-term stability is about 774 µg. PMID:26999157

  11. Development of scalable frequency and power Phase-Locked Loop in 130 nm CMOS technology

    NASA Astrophysics Data System (ADS)

    Firlej, M.; Fiutowski, T.; Idzik, M.; Moroń, J.; Świentek, K.

    2014-02-01

    The design and measurements results of a prototype very low power Phase-Locked Loop (PLL) ASIC for applications in readout systems of particle physics detectors are presented. The PLL was fabricated in 130 nm CMOS technology. It was designed and simulated for frequency range 10 MHz-3.5 GHz. Four division factors i.e. 6, 8, 10 and 16 were implemented in the PLL feedback loop. The main PLL block-voltage controlled oscillator (VCO) should work in 16 frequency ranges/modes, switched either manually or automatically. Preliminary measurements done in frequency range 20 MHz-1.6 GHz showed that the ASIC is functional and generates proper clock signal. The automatic VCO mode switching, one of the main design goals, was positively verified. Power consumption of around 0.6 mW was measured at 1 GHz for a division factor equal to 10.

  12. A Novel Digital Closed Loop MEMS Accelerometer Utilizing a Charge Pump.

    PubMed

    Chu, Yixing; Dong, Jingxin; Chi, Baoyong; Liu, Yunfeng

    2016-01-01

    This paper presents a novel digital closed loop microelectromechanical system (MEMS) accelerometer with the architecture and experimental evaluation. The complicated timing diagram or complex power supply in published articles are circumvented by using a charge pump system of adjustable output voltage fabricated in a 2P4M 0.35 µm complementary metal-oxide semiconductor (CMOS) process, therefore making it possible for interface circuits of MEMS accelerometers to be integrated on a single die on a large scale. The output bitstream of the sigma delta modulator is boosted by the charge pump system and then applied on the feedback comb fingers to form electrostatic forces so that the MEMS accelerometer can operate in a closed loop state. Test results agree with the theoretical formula nicely. The nonlinearity of the accelerometer within ±1 g is 0.222% and the long-term stability is about 774 µg. PMID:26999157

  13. Beam-based Feedback for the Linac Coherent Light Source

    SciTech Connect

    Fairley, D.; Allison, S.; Chevtsov, S.; Chu, P.; Decker, F.J.; Emma, P.; Frisch, J.; Himel, T.; Kim, K.; Krejcik, P.; Loos, H.; Lahey, T.; Natampalli, P.; Peng, S.; Rogind, D.; Shoaee, H.; Straumann, T.; Williams, E.; White, G.; Wu, J.; Zelazney, M.; /SLAC

    2010-02-11

    Beam-based feedback control loops are required by the Linac Coherent Light Source (LCLS) program in order to provide fast, single-pulse stabilization of beam parameters. Eight transverse feedback loops, a 6 x 6 longitudinal feedback loop, and a loop to maintain the electron bunch charge were successfully prototyped in MATLAB for the LCLS, and have been maintaining stability of the LCLS electron beam at beam rates up to 30Hz. In the final commissioning phase of LCLS the beam will be operating at up to 120Hz. In order to run the feedback loops at beam rate, the feedback loops will be implemented in EPICS IOCs with a dedicated ethernet multi-cast network. This paper will discuss the design of the beam-based Fast Feedback System for LCLS. Topics include MATLAB feedback prototyping, algorithm for 120Hz feedback, network design for fast data transport, actuator and sensor design for single-pulse control and sensor readback, and feedback configuration and runtime control.

  14. Reversed field pinch operation with intelligent shell feedback control in EXTRAP T2R

    NASA Astrophysics Data System (ADS)

    Brunsell, P. R.; Kuldkepp, M.; Menmuir, S.; Cecconello, M.; Hedqvist, A.; Yadikin, D.; Drake, J. R.; Rachlew, E.

    2006-11-01

    Discharges in the thin shell reversed field pinch (RFP) device EXTRAP T2R without active feedback control are characterized by growth of non-resonant m = 1 unstable resistive wall modes (RWMs) in agreement with linear MHD theory. Resonant m = 1 tearing modes (TMs) exhibit initially fast rotation and the associated perturbed radial fields at the shell are small, but eventually TMs wall-lock and give rise to a growing radial field. The increase in the radial field at the wall due to growing RWMs and wall-locked TMs is correlated with an increase in the toroidal loop voltage, which leads to discharge termination after 3-4 wall times. An active magnetic feedback control system has been installed in EXTRAP T2R. A two-dimensional array of 128 active saddle coils (pair-connected into 64 independent m = 1 coils) is used with intelligent shell feedback control to suppress the m = 1 radial field at the shell. With feedback control, active stabilization of the full toroidal spectrum of 16 unstable m = 1 non-resonant RWMs is achieved, and TM wall locking is avoided. A three-fold extension of the pulse length, up to the power supply limit, is observed. Intelligent shell feedback control is able to maintain the plasma equilibrium for 10 wall times, with plasma confinement parameters sustained at values comparable to those obtained in thick shell devices of similar size.

  15. Multiloop Rapid-Rise/Rapid Fall High-Voltage Power Supply

    NASA Technical Reports Server (NTRS)

    Bearden, Douglas

    2007-01-01

    A proposed multiloop power supply would generate a potential as high as 1.25 kV with rise and fall times <100 s. This power supply would, moreover, be programmable to generate output potentials from 20 to 1,250 V and would be capable of supplying a current of at least 300 A at 1,250 V. This power supply is intended to be a means of electronic shuttering of a microchannel plate that would be used to intensify the output of a charge-coupled-device imager to obtain exposure times as short as 1 ms. The basic design of this power supply could also be adapted to other applications in which high voltages and high slew rates are needed. At the time of reporting the information for this article, there was no commercially available power supply capable of satisfying the stated combination of voltage, rise-time, and fall-time requirements. The power supply would include a preregulator that would be used to program a voltage 1/30 of the desired output voltage. By means of a circuit that would include a pulse-width modulator (PWM), two voltage doublers, and a transformer having two primary and two secondary windings, the preregulator output voltage would be amplified by a factor of 30. A resistor would limit the current by controlling a drive voltage applied to field-effect transistors (FETs) during turn-on of the PWM. Two feedback loops would be used to regulate the high output voltage. A pulse transformer would be used to turn on four FETs to short-circuit output capacitors when the outputs of the PWM were disabled. Application of a 0-to-5-V square to a PWM shut-down pin would cause a 20-to-1,250-V square wave to appear at the output.

  16. Closed-Loop Neuroscience and Non-Invasive Brain Stimulation: A Tale of Two Loops

    PubMed Central

    Zrenner, Christoph; Belardinelli, Paolo; Müller-Dahlhaus, Florian; Ziemann, Ulf

    2016-01-01

    Closed-loop neuroscience is receiving increasing attention with recent technological advances that enable complex feedback loops to be implemented with millisecond resolution on commodity hardware. We summarize emerging conceptual and methodological frameworks that are available to experimenters investigating a “brain in the loop” using non-invasive brain stimulation and briefly review the experimental and therapeutic implications. We take the view that closed-loop neuroscience in fact deals with two conceptually quite different loops: a “brain-state dynamics” loop, used to couple with and modulate the trajectory of neuronal activity patterns, and a “task dynamics” loop, that is the bidirectional motor-sensory interaction between brain and (simulated) environment, and which enables goal-directed behavioral tasks to be incorporated. Both loops need to be considered and combined to realize the full experimental and therapeutic potential of closed-loop neuroscience. PMID:27092055

  17. Closed-Loop, Multichannel Experimentation Using the Open-Source NeuroRighter Electrophysiology Platform.

    PubMed

    Newman, Jonathan P; Zeller-Townson, Riley; Fong, Ming-Fai; Arcot Desai, Sharanya; Gross, Robert E; Potter, Steve M

    2012-01-01

    Single neuron feedback control techniques, such as voltage clamp and dynamic clamp, have enabled numerous advances in our understanding of ion channels, electrochemical signaling, and neural dynamics. Although commercially available multichannel recording and stimulation systems are commonly used for studying neural processing at the network level, they provide little native support for real-time feedback. We developed the open-source NeuroRighter multichannel electrophysiology hardware and software platform for closed-loop multichannel control with a focus on accessibility and low cost. NeuroRighter allows 64 channels of stimulation and recording for around US $10,000, along with the ability to integrate with other software and hardware. Here, we present substantial enhancements to the NeuroRighter platform, including a redesigned desktop application, a new stimulation subsystem allowing arbitrary stimulation patterns, low-latency data servers for accessing data streams, and a new application programming interface (API) for creating closed-loop protocols that can be inserted into NeuroRighter as plugin programs. This greatly simplifies the design of sophisticated real-time experiments without sacrificing the power and speed of a compiled programming language. Here we present a detailed description of NeuroRighter as a stand-alone application, its plugin API, and an extensive set of case studies that highlight the system's abilities for conducting closed-loop, multichannel interfacing experiments. PMID:23346047

  18. Closed-Loop, Multichannel Experimentation Using the Open-Source NeuroRighter Electrophysiology Platform

    PubMed Central

    Newman, Jonathan P.; Zeller-Townson, Riley; Fong, Ming-Fai; Arcot Desai, Sharanya; Gross, Robert E.; Potter, Steve M.

    2013-01-01

    Single neuron feedback control techniques, such as voltage clamp and dynamic clamp, have enabled numerous advances in our understanding of ion channels, electrochemical signaling, and neural dynamics. Although commercially available multichannel recording and stimulation systems are commonly used for studying neural processing at the network level, they provide little native support for real-time feedback. We developed the open-source NeuroRighter multichannel electrophysiology hardware and software platform for closed-loop multichannel control with a focus on accessibility and low cost. NeuroRighter allows 64 channels of stimulation and recording for around US $10,000, along with the ability to integrate with other software and hardware. Here, we present substantial enhancements to the NeuroRighter platform, including a redesigned desktop application, a new stimulation subsystem allowing arbitrary stimulation patterns, low-latency data servers for accessing data streams, and a new application programming interface (API) for creating closed-loop protocols that can be inserted into NeuroRighter as plugin programs. This greatly simplifies the design of sophisticated real-time experiments without sacrificing the power and speed of a compiled programming language. Here we present a detailed description of NeuroRighter as a stand-alone application, its plugin API, and an extensive set of case studies that highlight the system’s abilities for conducting closed-loop, multichannel interfacing experiments. PMID:23346047

  19. Loop-to-loop coupling.

    SciTech Connect

    Warne, Larry Kevin; Lucero, Larry Martin; Langston, William L.; Salazar, Robert Austin; Coleman, Phillip Dale; Basilio, Lorena I.; Bacon, Larry Donald

    2012-05-01

    This report estimates inductively-coupled energy to a low-impedance load in a loop-to-loop arrangement. Both analytical models and full-wave numerical simulations are used and the resulting fields, coupled powers and energies are compared. The energies are simply estimated from the coupled powers through approximations to the energy theorem. The transmitter loop is taken to be either a circular geometry or a rectangular-loop (stripline-type) geometry that was used in an experimental setup. Simple magnetic field models are constructed and used to estimate the mutual inductance to the receiving loop, which is taken to be circular with one or several turns. Circuit elements are estimated and used to determine the coupled current and power (an equivalent antenna picture is also given). These results are compared to an electromagnetic simulation of the transmitter geometry. Simple approximate relations are also given to estimate coupled energy from the power. The effect of additional loads in the form of attached leads, forming transmission lines, are considered. The results are summarized in a set of susceptibility-type curves. Finally, we also consider drives to the cables themselves and the resulting common-to-differential mode currents in the load.

  20. Rogowski Loop design for NSTX

    SciTech Connect

    McCormack, B.; Kaita, R.; Kugel, H.; Hatcher, R.

    2000-01-06

    The Rogowski Loop is one of the most basic diagnostics for tokamak operations. On the National Spherical Torus Experiment (NSTX), the plasma current Rogowski Loop had the constraints of the very limited space available on the center stack, 5,000 volt isolation, flexibility requirements as it remained a part of the Center Stack assembly after the first phase of operation, and a +120 C temperature requirement. For the second phase of operation, four Halo Current Rogowski Loops under the Center Stack tiles will be installed having +600 C and limited space requirements. Also as part of the second operational phase, up to ten Rogowski Loops will installed to measure eddy currents in the Passive Plate support structures with +350 C, restricted space, and flexibility requirements. This presentation will provide the details of the material selection, fabrication techniques, testing, and installation results of the Rogowski Loops that were fabricated for the high temperature operational and bakeout requirements, high voltage isolation requirements, and the space and flexibility requirements imposed upon the Rogowski Loops. In the future operational phases of NSTX, additional Rogowski Loops could be anticipated that will measure toroidal plasma currents in the vacuum vessel and in the Passive Plate assemblies.

  1. A multiple-pass ring oscillator based dual-loop phase-locked loop

    NASA Astrophysics Data System (ADS)

    Danfeng, Chen; Junyan, Ren; Jingjing, Deng; Wei, Li; Ning, Li

    2009-10-01

    A dual-loop phase-locked loop (PLL) for wideband operation is proposed. The dual-loop architecture combines a coarse-tuning loop with a fine-tuning one, enabling a wide tuning range and low voltage-controlled oscillator (VCO) gain without poisoning phase noise and reference spur suppression performance. An analysis of the phase noise and reference spur of the dual-loop PLL is emphasized. A novel multiple-pass ring VCO is designed for the dual-loop application. It utilizes both voltage-control and current-control simultaneously in the delay cell. The PLL is fabricated in Jazz 0.18-μm RF CMOS technology. The measured tuning range is from 4.2 to 5.9 GHz. It achieves a low phase noise of -99 dBc/Hz @ 1 MHz offset from a 5.5 GHz carrier.

  2. Closed-loop fiber optic gyroscope with homodyne detection

    NASA Astrophysics Data System (ADS)

    Zhu, Yong; Qin, BingKun; Chen, Shufen

    1996-09-01

    Interferometric fiber optic gyroscope (IFOG) has been analyzed with autocontrol theory in this paper. An open-loop IFOG system is not able to restrain the bias drift, but a closed-loop IFOG system can do it very well using negative feedback in order to suppress zero drift. The result of our theoretic analysis and computer simulation indicate that the bias drift of a closed-loop system is smaller than an open- loop one.

  3. Loop Input.

    ERIC Educational Resources Information Center

    Woodward, Tessa

    2003-01-01

    Discusses loop input, a specific type of experiential teacher training process that involves an alignment of the process and content of learning. This concept has gradually gained ground in English language teacher training since 1986 when the term was coined. (Author/VWL)

  4. Iterative LQG Controller Design Through Closed-Loop Identification

    NASA Technical Reports Server (NTRS)

    Hsiao, Min-Hung; Huang, Jen-Kuang; Cox, David E.

    1996-01-01

    This paper presents an iterative Linear Quadratic Gaussian (LQG) controller design approach for a linear stochastic system with an uncertain open-loop model and unknown noise statistics. This approach consists of closed-loop identification and controller redesign cycles. In each cycle, the closed-loop identification method is used to identify an open-loop model and a steady-state Kalman filter gain from closed-loop input/output test data obtained by using a feedback LQG controller designed from the previous cycle. Then the identified open-loop model is used to redesign the state feedback. The state feedback and the identified Kalman filter gain are used to form an updated LQC controller for the next cycle. This iterative process continues until the updated controller converges. The proposed controller design is demonstrated by numerical simulations and experiments on a highly unstable large-gap magnetic suspension system.

  5. Closed-loop control of a core free rolled EAP actuator

    NASA Astrophysics Data System (ADS)

    Sarban, Rahimullah; Oubaek, Jakob; Jones, Richard W.

    2009-03-01

    Tubular dielectric electro-active polymer actuators, also referred as tubular InLastors, have many possible applications. One of the most obvious is as a positioning push-type device. This work examines the feedback closed-loop control of a core-free tubular InLastor fabricated from sheets of PolyPowerTM, an EAP material developed by Danfoss PolyPower A/S, which uses a silicone elastomer in conjunction with smart compliant electrode technology. This is part of an ongoing study to develop a precision positioning feedback control system for this device. Initially proportional and integral (PI) control is considered to provide position control of the tubular InLastor. Control of the tubular Inlastors require more than conventional control, used for linear actuators, because the InLastors display highly nonlinear static voltage-strain and voltage-force characteristics as well as dynamic hysteresis and time-dependent strain behavior. In an attempt to overcome the nonlinear static voltage-strain characteristics of the Inlastors and for improving the dynamic performance of the controlled device, a gain scheduling algorithm is then integrated into the PI controlled system.

  6. Low distortion automatic phase control circuit. [voltage controlled phase shifter

    NASA Technical Reports Server (NTRS)

    Hauge, G.; Pederson, C. W. (Inventor)

    1974-01-01

    A voltage controlled phase shifter is rendered substantially harmonic distortion free over a large dynamic input range by employing two oppositely poled, equally biased varactor diodes as the voltage controlled elements which adjust the phase shift. Control voltages which affect the bias of both diodes equally are used to adjust the phase shift without increasing distortion. A feedback stabilized phase shifter is rendered substantially frequency independent by employing a phase detector to control the phase shift of the voltage controlled phase shifter.

  7. Single SQUID multiplexer for arrays of voltage-biased superconducting bolometers

    SciTech Connect

    Yoon, Jongsoo; Clarke, John; Gildemeister, J.M.; Lee, Adrian T.; Myers, M.J.; Richards, P.L.; Skidmore, J.T.; Spieler, H.G.

    2001-08-20

    We describe a frequency domain superconducting quantum interference device (SQUID) multiplexer which monitors a row of low-temperature sensors simultaneously with a single SQUID. Each sensor is ac biased with a unique frequency and all the sensor currents are added in a superconducting summing loop. A single SQUID measures the current in the summing loop, and the individual signals are lock-in detected after the room temperature SQUID electronics. The current in the summing loop is nulled by feedback to eliminate direct crosstalk. In order to avoid the accumulation of Johnson noise in the summing loop, a tuned bandpass filter is inserted in series with each sensor. For a 32-channel multiplexer for Voltage-biased Superconducting Bolometer (VSB) with a time constant {approx}1msec, we estimate that bias frequencies in the range from {approx}500kHz to {approx}600kHz are practical. The major limitation of our multiplexing scheme is in the slew rate of a readout SQUID. We discuss a ''carrier nulling'' technique which could be used to increase the number of sensors in a row or to multiplex faster bolometers by reducing the required slew rate for a readout SQUID.

  8. Low power, scalable multichannel high voltage controller

    DOEpatents

    Stamps, James Frederick; Crocker, Robert Ward; Yee, Daniel Dadwa; Dils, David Wright

    2008-03-25

    A low voltage control circuit is provided for individually controlling high voltage power provided over bus lines to a multitude of interconnected loads. An example of a load is a drive for capillary channels in a microfluidic system. Control is distributed from a central high voltage circuit, rather than using a number of large expensive central high voltage circuits to enable reducing circuit size and cost. Voltage is distributed to each individual load and controlled using a number of high voltage controller channel switches connected to high voltage bus lines. The channel switches each include complementary pull up and pull down photo isolator relays with photo isolator switching controlled from the central high voltage circuit to provide a desired bus line voltage. Switching of the photo isolator relays is further controlled in each channel switch using feedback from a resistor divider circuit to maintain the bus voltage swing within desired limits. Current sensing is provided using a switched resistive load in each channel switch, with switching of the resistive loads controlled from the central high voltage circuit.

  9. Low power, scalable multichannel high voltage controller

    DOEpatents

    Stamps, James Frederick; Crocker, Robert Ward; Yee, Daniel Dadwa; Dils, David Wright

    2006-03-14

    A low voltage control circuit is provided for individually controlling high voltage power provided over bus lines to a multitude of interconnected loads. An example of a load is a drive for capillary channels in a microfluidic system. Control is distributed from a central high voltage circuit, rather than using a number of large expensive central high voltage circuits to enable reducing circuit size and cost. Voltage is distributed to each individual load and controlled using a number of high voltage controller channel switches connected to high voltage bus lines. The channel switches each include complementary pull up and pull down photo isolator relays with photo isolator switching controlled from the central high voltage circuit to provide a desired bus line voltage. Switching of the photo isolator relays is further controlled in each channel switch using feedback from a resistor divider circuit to maintain the bus voltage swing within desired limits. Current sensing is provided using a switched resistive load in each channel switch, with switching of the resistive loads controlled from the central high voltage circuit.

  10. Constant voltage electro-slag remelting control

    SciTech Connect

    Schlienger, M.E.

    1996-10-22

    A system for controlling electrode gap in an electro-slag remelt furnace has a constant regulated voltage and an electrode which is fed into the slag pool at a constant rate. The impedance of the circuit through the slag pool is directly proportional to the gap distance. Because of the constant voltage, the system current changes are inversely proportional to changes in gap. This negative feedback causes the gap to remain stable. 1 fig.

  11. Constant voltage electro-slag remelting control

    DOEpatents

    Schlienger, Max E.

    1996-01-01

    A system for controlling electrode gap in an electro-slag remelt furnace has a constant regulated voltage and an eletrode which is fed into the slag pool at a constant rate. The impedance of the circuit through the slag pool is directly proportional to the gap distance. Because of the constant voltage, the system current changes are inversely proportional to changes in gap. This negative feedback causes the gap to remain stable.

  12. Lp-stability (1 less than or equal to p less than or equal to infinity) of multivariable nonlinear time-varying feedback systems that are open-loop unstable. [noting unstable convolution subsystem forward control and time varying nonlinear feedback

    NASA Technical Reports Server (NTRS)

    Callier, F. M.; Desoer, C. A.

    1973-01-01

    A class of multivariable, nonlinear time-varying feedback systems with an unstable convolution subsystem as feedforward and a time-varying nonlinear gain as feedback was considered. The impulse response of the convolution subsystem is the sum of a finite number of increasing exponentials multiplied by nonnegative powers of the time t, a term that is absolutely integrable and an infinite series of delayed impulses. The main result is a theorem. It essentially states that if the unstable convolution subsystem can be stabilized by a constant feedback gain F and if incremental gain of the difference between the nonlinear gain function and F is sufficiently small, then the nonlinear system is L(p)-stable for any p between one and infinity. Furthermore, the solutions of the nonlinear system depend continuously on the inputs in any L(p)-norm. The fixed point theorem is crucial in deriving the above theorem.

  13. Indirect Identification of Linear Stochastic Systems with Known Feedback Dynamics

    NASA Technical Reports Server (NTRS)

    Huang, Jen-Kuang; Hsiao, Min-Hung; Cox, David E.

    1996-01-01

    An algorithm is presented for identifying a state-space model of linear stochastic systems operating under known feedback controller. In this algorithm, only the reference input and output of closed-loop data are required. No feedback signal needs to be recorded. The overall closed-loop system dynamics is first identified. Then a recursive formulation is derived to compute the open-loop plant dynamics from the identified closed-loop system dynamics and known feedback controller dynamics. The controller can be a dynamic or constant-gain full-state feedback controller. Numerical simulations and test data of a highly unstable large-gap magnetic suspension system are presented to demonstrate the feasibility of this indirect identification method.

  14. Feedback: Breakfast of Champions.

    ERIC Educational Resources Information Center

    Justman, Jeffrey J.

    Feedback is an important skill that people need to learn in life. Feedback is crucial in a public speaking class to improve speaking skills. Providing and receiving feedback is what champions feed on to be successful, thus feedback is called the "Breakfast of Champions." Feedback builds speakers' confidence. Providing in-depth feedback is also…

  15. CORESS feedback

    PubMed Central

    2012-01-01

    This edition of CORESS feedback reinforces the very basic principles of obtaining and using an accurate history and examination to make an appropriate diagnosis in the face of equivocal or uninformative investigations and failing equipment. Case 126 illustrates once again the potential deleterious consequences of failing to check a drug correctly prior to administration. We are grateful to the clinicians who have provided the material for these reports. The online reporting form is on our website (www.coress.org.uk), which also includes all previous feedback reports. Published contributions will be acknowledged by a ‘Certificate of Contribution’, which may be included in the contributor’s record of continuing professional development. CORESS relies heavily on the expertise of the specialty members of the Advisory Board in the preparation of feedback reports and dissemination of safety information related to surgical practice. The organisation is grateful to the following members of the Advisory Board and Board of Directors who have contributed to published reports in 2010 and 2011: Board of Directors: Viscount Bridgeman, Mr Chris Chilton, Mr Martin Else, Professor Nicholas Gair, Mr Adam Lewis CVO, Miss Clare Marx, Mr Andrew May, Lord Bernard Ribeiro, Mr Frank Smith, Mr Peter Tait, Mr Denis Wilkins. Advisory Board: Ms E Baird, Mr Daryl I Baker, Mr Ken Catchpole, Dr Lauren Morgan, Mr Stephen Clark, Mr Robert Davies, Mr Mark Deakin, Ms D Eastwood, Mr Barry Ferris, Mr Mark Fordham, Mr Paul J Gibbs, Mr Grey Giddins, Mr Robert Greatorex, Mr Mervyn Griffiths, Mr John Hammond, Mr William Harkness, Mr M Hemadri, Mr Richard Holdsworth, Miss Claire Hopkins, Professor Zygmunt Krukowski, Mr N Mamode, Mr Ian Martin, Surgeon Commander Mark Midwinter, Mr J Richard Novell, Professor Gerald O’Sullivan, Dr Gerard Panting, Mr Mike Pittam, Dr Mike Powers QC, Ms Patricia Scott, Professor Alastair Thompson, Dr J P van Besouw, Mr Mark Vipond, Mr David Webster, Mr Michael Wyatt.

  16. Closed-loop pulsed helium ionization detector

    DOEpatents

    Ramsey, Roswitha S.; Todd, Richard A.

    1987-01-01

    A helium ionization detector for gas chromatography is operated in a constant current, pulse-modulated mode by configuring the detector, electrometer and a high voltage pulser in a closed-loop control system. The detector current is maintained at a fixed level by varying the frequency of fixed-width, high-voltage bias pulses applied to the detector. An output signal proportional to the pulse frequency is produced which is indicative of the charge collected for a detected species.

  17. A battery-based, low-noise voltage source

    NASA Astrophysics Data System (ADS)

    Wagner, Anke; Sturm, Sven; Schabinger, Birgit; Blaum, Klaus; Quint, Wolfgang

    2010-06-01

    A highly stable, low-noise voltage source was designed to improve the stability of the electrode bias voltages of a Penning trap. To avoid excess noise and ground loops, the voltage source is completely independent of the public electric network and uses a 12 V car battery to generate output voltages of ±15 and ±5 V. First, the dc supply voltage is converted into ac-voltage and gets amplified. Afterwards, the signal is rectified, filtered, and regulated to the desired output value. Each channel can deliver up to 1.5 A. The current as well as the battery voltage and the output voltages can be read out via a universal serial bus (USB) connection for monitoring purposes. With the presented design, a relative voltage stability of 7×10-7 over 6.5 h and a noise level equal or smaller than 30 nV/√Hz is achieved.

  18. Kalman Orbit Optimized Loop Tracking

    NASA Technical Reports Server (NTRS)

    Young, Lawrence E.; Meehan, Thomas K.

    2011-01-01

    Under certain conditions of low signal power and/or high noise, there is insufficient signal to noise ratio (SNR) to close tracking loops with individual signals on orbiting Global Navigation Satellite System (GNSS) receivers. In addition, the processing power available from flight computers is not great enough to implement a conventional ultra-tight coupling tracking loop. This work provides a method to track GNSS signals at very low SNR without the penalty of requiring very high processor throughput to calculate the loop parameters. The Kalman Orbit-Optimized Loop (KOOL) tracking approach constitutes a filter with a dynamic model and using the aggregate of information from all tracked GNSS signals to close the tracking loop for each signal. For applications where there is not a good dynamic model, such as very low orbits where atmospheric drag models may not be adequate to achieve the required accuracy, aiding from an IMU (inertial measurement unit) or other sensor will be added. The KOOL approach is based on research JPL has done to allow signal recovery from weak and scintillating signals observed during the use of GPS signals for limb sounding of the Earth s atmosphere. That approach uses the onboard PVT (position, velocity, time) solution to generate predictions for the range, range rate, and acceleration of the low-SNR signal. The low- SNR signal data are captured by a directed open loop. KOOL builds on the previous open loop tracking by including feedback and observable generation from the weak-signal channels so that the MSR receiver will continue to track and provide PVT, range, and Doppler data, even when all channels have low SNR.

  19. Feedback control for penetrating a downburst

    NASA Technical Reports Server (NTRS)

    Bryson, Arthur E., Jr.; Zhao, Yiyuan

    1987-01-01

    Feedback logic is given that produces satisfactory penetration of an aircraft through a severe downburst. The logic has two parts: (1) A switch that calls for full throttle and tight climb-rate-hold feedback logic when the magnitude of headwind-rate exceeds a threshold level; this switch stays on until re-set by the pilot after penetration of the downburst. (2) A tight climb-rate-hold autopilot, using feedback of pitch-angle to angle-of-attack. After penetration, recovery to steady climbing flight is aided by using feedback of airspeed deviation to throttle. Insights on control strategy are gained from an analysis of energy changes during flight through a downburst. Closed-loop simulations are given for a 727 aircraft penetrating severe downbursts on take-off. Boeing's recommendation of constant pitch angle was confirmed as an excellent feedback control strategy.

  20. Feedbacks and landscape-level vegetation dynamics.

    PubMed

    Bowman, David M J S; Perry, George L W; Marston, J B

    2015-05-01

    Alternative stable-state theory (ASS) is widely accepted as explaining landscape-level vegetation dynamics, such as switches between forest and grassland. This theory argues that webs of feedbacks stabilise vegetation composition and structure, and that abrupt state shifts can occur if stabilising feedbacks are weakened. However, it is difficult to identify stabilising feedback loops and the disturbance thresholds beyond which state changes occur. Here, we argue that doing this requires a synthetic approach blending observation, experimentation, simulation, conceptual models, and narratives. Using forest boundaries and large mammal extinctions, we illustrate how a multifaceted research program can advance understanding of feedback-driven ecosystem change. Our integrative approach has applicability to other complex macroecological systems controlled by numerous feedbacks where controlled experimentation is impossible. PMID:25837918

  1. A dual-loop model of the human controller

    NASA Technical Reports Server (NTRS)

    Hess, R. A.

    1977-01-01

    A representative model of the human controller in single-axis compensatory tracking tasks that exhibits an internal feedback loop which is not evident in single-loop models now in common use is presented. This hypothetical inner-loop involves a neuromuscular command signal derived from the time rate of change of controlled element output which is due to control activity. It is not contended that the single-loop human controller models now in use are incorrect, but that they contain an implicit but important internal loop closure, which, if explicitly considered, can account for a good deal of the adaptive nature of the human controller in a systematic manner.

  2. Feasibility Study of a 6.6kV, 1MW Transformerless BTB-Based Loop Controller

    NASA Astrophysics Data System (ADS)

    Yonetani, Shinsuke; Fujita, Hideaki; Akagi, Hirofumi; Okada, Naotaka

    This paper achieves a feasibility study of a 6.6kV, 1MW loop controller that consists of a transformerless back-to-back configuration using two 5-level diode-clamped converters. However, the loop controller requires reducing the zero-sequence current circulating between the two distribution lines below than 0.2 A in rms, in order to avoid malfunction of line-to-ground fault protection relays. Moreover, all the dc voltages across four capacitors in the dc link have to be controlled equally. This paper presents a solution to these problems. Two common-mode chokes are installed at the ac side of each converter to suppress high-frequency zero-sequence currents, while feedback control is applied to eliminate low-frequency zero-sequence currents. Two bidirectional buck-boost dc-dc converters are employed to keep the four capacitor voltages equal. Simulation results verify viability and effectiveness of the loop controller, along with the developed theoretical analysis.

  3. Beam-based Feedback Testing and Simulations for the SLC Linac

    SciTech Connect

    Hendrickson, Linda

    2000-09-05

    Beam-based feedback systems were a key element in the successful operation of the Stanford Linear Collider (SLC) but the performance was not optimal. Some limitations were incomplete communication between the feedback loops, slow correctors, and constraints on the placement of feedback devices. Recent beam experiments and simulations have improved understanding of feedback performance characteristics, and increased confidence in designing feedback systems for the Next Linear Collider (NLC).

  4. Feedback regulation in cell signalling: Lessons for cancer therapeutics.

    PubMed

    Nguyen, Lan K; Kholodenko, Boris N

    2016-02-01

    The notion of feedback is fundamental for understanding signal transduction networks. Feedback loops attenuate or amplify signals, change the network dynamics and modify the input-output relationships between the signal and the target. Negative feedback provides robustness to noise and adaptation to perturbations, but as a double-edged sword can prevent effective pathway inhibition by a drug. Positive feedback brings about switch-like network responses and can convert analog input signals into digital outputs, triggering cell fate decisions and phenotypic changes. We show how a multitude of protein-protein interactions creates hidden feedback loops in signal transduction cascades. Drug treatments that interfere with feedback regulation can cause unexpected adverse effects. Combinatorial molecular interactions generated by pathway crosstalk and feedback loops often bypass the block caused by targeted therapies against oncogenic mutated kinases. We discuss mechanisms of drug resistance caused by network adaptations and suggest that development of effective drug combinations requires understanding of how feedback loops modulate drug responses. PMID:26481970

  5. Direct laser additive fabrication system with image feedback control

    DOEpatents

    Griffith, Michelle L.; Hofmeister, William H.; Knorovsky, Gerald A.; MacCallum, Danny O.; Schlienger, M. Eric; Smugeresky, John E.

    2002-01-01

    A closed-loop, feedback-controlled direct laser fabrication system is disclosed. The feedback refers to the actual growth conditions obtained by real-time analysis of thermal radiation images. The resulting system can fabricate components with severalfold improvement in dimensional tolerances and surface finish.

  6. Rollercoaster Loop Shapes

    ERIC Educational Resources Information Center

    Pendrill, Ann-Marie

    2005-01-01

    Many modern rollercoasters feature loops. Although textbook loops are often circular, real rollercoaster loops are not. In this paper, we look into the mathematical description of various possible loop shapes, as well as their riding properties. We also discuss how a study of loop shapes can be used in physics education.

  7. Feedback linearization for control of air breathing engines

    NASA Technical Reports Server (NTRS)

    Phillips, Stephen; Mattern, Duane

    1991-01-01

    The method of feedback linearization for control of the nonlinear nozzle and compressor components of an air breathing engine is presented. This method overcomes the need for a large number of scheduling variables and operating points to accurately model highly nonlinear plants. Feedback linearization also results in linear closed loop system performance simplifying subsequent control design. Feedback linearization is used for the nonlinear partial engine model and performance is verified through simulation.

  8. Air Force research in human sensory feedback for telepresence

    NASA Technical Reports Server (NTRS)

    Julian, Ronald G.

    1993-01-01

    Telepresence operations require high quality information transfer between the human master and the remotely located slave. Present Air Force research focuses on the human aspects of the information needed to complete the control/feedback loop. Work in three key areas of human sensory feedback for manipulation of objects are described. Specific projects in each key area are outlined, including research tools (hardware), planned research, and test results. Nonmanipulative feedback technologies are mentioned to complete the advanced teleoperation discussions.

  9. Feedback linearization of power amplifiers for digital microwave communications

    NASA Astrophysics Data System (ADS)

    Weaver, C. F.; Taylor, D. P.

    A new method of linearizing high capacity microwave radio power amplifiers (PA) is presented. This method which is mainly applicable to GaAs FET PA's, uses feedback around a linear quadrature amplitude modulation (QAM) modulator, a PA, and a linear coherent QAM demodulator. A simulation model is given and simulations are presented to demonstrate the improvement over unlinearized PA's. Loop stability is discussed and the peak eye closure performance versus PA input power, loop gain, and loop bandwidth are presented.

  10. Time-Delayed Quantum Feedback Control.

    PubMed

    Grimsmo, Arne L

    2015-08-01

    A theory of time-delayed coherent quantum feedback is developed. More specifically, we consider a quantum system coupled to a bosonic reservoir creating a unidirectional feedback loop. It is shown that the dynamics can be mapped onto a fictitious series of cascaded quantum systems, where the system is driven by past versions of itself. The derivation of this model relies on a tensor network representation of the system-reservoir time propagator. For concreteness, this general theory is applied to a driven two-level atom scattering into a coherent feedback loop. We demonstrate how delay effects can qualitatively change the dynamics of the atom and how quantum control can be implemented in the presence of time delays. PMID:26296104

  11. Time-Delayed Quantum Feedback Control

    NASA Astrophysics Data System (ADS)

    Grimsmo, Arne L.

    2015-08-01

    A theory of time-delayed coherent quantum feedback is developed. More specifically, we consider a quantum system coupled to a bosonic reservoir creating a unidirectional feedback loop. It is shown that the dynamics can be mapped onto a fictitious series of cascaded quantum systems, where the system is driven by past versions of itself. The derivation of this model relies on a tensor network representation of the system-reservoir time propagator. For concreteness, this general theory is applied to a driven two-level atom scattering into a coherent feedback loop. We demonstrate how delay effects can qualitatively change the dynamics of the atom and how quantum control can be implemented in the presence of time delays.

  12. Feedback control for stabilizing chaotic spiral waves during cardiac ventricular fibrillation

    NASA Astrophysics Data System (ADS)

    Uzelac, Ilija; Wikswo, John; Gray, Richard

    2011-03-01

    The cardiac arrhythmias that lead to ventricular fibrillation (VF) arise from electrical spiral waves (SW) rotating within the heart with a characteristic period τ . A single drifting SW can degenerate into a chaotic system of multiple SWs and VF. Hence early SW detection and termination is crucial to prevent VF. Time-delayed feedback control (TDFC) is well known approach for stabilizing unstable periodic orbits embedded in chaotic attractors. We hypothesize that cardiac SWs can be stabilized by TDFC with a time-delay of τ . Implementing this approach will require precise, closed-loop control of the charge delivered to the heart during the defibrillation process. To do this, we have developed a 2 kW arbitrary-waveform voltage-to-current converter (V2CC) with a 1 kHz bandwidth that can deliver up to 5 A at 400 V for 500 ms, and a photodiode system for recording in real time an optical electrocardiogram, OECG(t). The feedback signal driving the V2CC will be the time-difference (OECG(t) - OECG(t-T), where we hypothesize that T is τ , the period of the SW. This may dramatically decrease defibrillation voltages by using a defibrillation waveform customized to the VF event, unlike commercial capacitor defibrillators. Supported in part by NIH R01 HL58241-11 through ARRA 2009.

  13. Water Stream "Loop-the-Loop"

    ERIC Educational Resources Information Center

    Jefimenko, Oleg

    1974-01-01

    Discusses the design of a modified loop-the-loop apparatus in which a water stream is used to illustrate centripetal forces and phenomena of high-velocity hydrodynamics. Included are some procedures of carrying out lecture demonstrations. (CC)

  14. Low voltage surface transverse wave oscillators for the next generation CMOS technology.

    PubMed

    Avramov, Ivan D

    2005-08-01

    The design and performance of voltage controlled surface transverse wave oscillators (VCSTWO) in the lower gigahertz frequency range, operating on supply and tuning voltages in the 1.2 to 3.3 V range, and suitable for direct interfacing with the next generation CMOS circuits are presented. By applying the "boost" principle, as used in direct current (DC)-DC converters, to the design of the sustaining amplifier, the VCSTWO outputs are switched between 0 V and a positive peak value, exceeding the supply voltage Us, to provide safe CMOS-circuit switching while keeping the radio frequency (RF)/DC efficiency to a maximum for low DC power consumption. The investigated 1.0 and 2.5 GHz VCSTWO are varactor tuned feedback-loop oscillators stabilized with two-port surface transverse wave (STW) resonators. Each VCSTWO has a DC-coupled, high-impedance switched output to drive the CMOS circuit directly, and an additional sinusoidal 50 ohmz high-power reference output available for other low-noise system applications. Phase noise levels in the -103 to -115 dBc/Hz range at 1 kHz carrier offset are achieved with 1.0 GHz VCSTWO at a RF/DC efficiency in the 21 to 29% range. The 2.5 GHz prototypes demonstrate phase noise levels in the -97 to -102 dBc/Hz range at 1 kHz carrier offset, and efficiencies range between 8 and 15%. PMID:16245594

  15. Programmable high voltage power supply with regulation confined to the high voltage section

    NASA Technical Reports Server (NTRS)

    Castell, Karen D. (Inventor); Ruitberg, Arthur P. (Inventor)

    1994-01-01

    A high voltage power supply in a dc-dc converter configuration includes a pre-regulator which filters and regulates the dc input and drives an oscillator which applies, in turn, a low voltage ac signal to the low side of a step-up high voltage transformer. The high voltage side of the transformer drives a voltage multiplier which provides a stepped up dc voltage to an output filter. The output voltage is sensed by a feedback network which then controls a regulator. Both the input and output of the regulator are on the high voltage side, avoiding isolation problems. The regulator furnishes a portion of the drive to the voltage multiplier, avoiding having a regulator in series with the load with its attendant, relatively high power losses. This power supply is highly regulated, has low power consumption, a low parts count and may be manufactured at low cost. The power supply has a programmability feature that allows for the selection of a large range of output voltages.

  16. Causal Loop Analysis of coastal geomorphological systems

    NASA Astrophysics Data System (ADS)

    Payo, Andres; Hall, Jim W.; French, Jon; Sutherland, James; van Maanen, Barend; Nicholls, Robert J.; Reeve, Dominic E.

    2016-03-01

    As geomorphologists embrace ever more sophisticated theoretical frameworks that shift from simple notions of evolution towards single steady equilibria to recognise the possibility of multiple response pathways and outcomes, morphodynamic modellers are facing the problem of how to keep track of an ever-greater number of system feedbacks. Within coastal geomorphology, capturing these feedbacks is critically important, especially as the focus of activity shifts from reductionist models founded on sediment transport fundamentals to more synthesist ones intended to resolve emergent behaviours at decadal to centennial scales. This paper addresses the challenge of mapping the feedback structure of processes controlling geomorphic system behaviour with reference to illustrative applications of Causal Loop Analysis at two study cases: (1) the erosion-accretion behaviour of graded (mixed) sediment beds, and (2) the local alongshore sediment fluxes of sand-rich shorelines. These case study examples are chosen on account of their central role in the quantitative modelling of geomorphological futures and as they illustrate different types of causation. Causal loop diagrams, a form of directed graph, are used to distil the feedback structure to reveal, in advance of more quantitative modelling, multi-response pathways and multiple outcomes. In the case of graded sediment bed, up to three different outcomes (no response, and two disequilibrium states) can be derived from a simple qualitative stability analysis. For the sand-rich local shoreline behaviour case, two fundamentally different responses of the shoreline (diffusive and anti-diffusive), triggered by small changes of the shoreline cross-shore position, can be inferred purely through analysis of the causal pathways. Explicit depiction of feedback-structure diagrams is beneficial when developing numerical models to explore coastal morphological futures. By explicitly mapping the feedbacks included and neglected within a model, the modeller can readily assess if critical feedback loops are included.

  17. Offset quadrature communications with decision-feedback carrier synchronization

    NASA Technical Reports Server (NTRS)

    Simon, M. K.; Smith, J. G.

    1974-01-01

    In order to accommodate a quadrature amplitude-shift-keyed (QASK) signal, Simon and Smith (1974) have modified the decision-feedback loop which tracks a quadrature phase-shift-keyed (QPSK). In the investigation reported approaches are considered to modify the loops in such a way that offset QASK signals can be tracked, giving attention to the special case of an offset QPSK. The development of the stochastic integro-differential equation of operation for a decision-feedback offset QASK loop is discussed along with the probability density function of the phase error process.

  18. Precision voltage regulator

    NASA Technical Reports Server (NTRS)

    Hand, P. J.; Crawford, R. A.

    1972-01-01

    Balanced positive and negative voltage output circuit, in which error voltage for control is developed from difference in absolute value of positive and negative voltages referenced to a common point, regulates voltage for use with inertial reference unit. Fast-acting, temperature-compensated, high-gain operational amplifier circuits maintain common point.

  19. Feedback stitching for gigapixel video

    NASA Astrophysics Data System (ADS)

    Marks, Daniel L.; Bange, Lauren M.; Brady, David J.

    2015-11-01

    Methods of stitching static panoramas are unsuitable for video-rate stitching from camera arrays, because these methods are too computationally intensive for real-time operation and do not take advantage of prior knowledge of camera positions or the coherence between successive frames of a video sequence. We propose feedback stitching, which embeds the stitching process in a feedback loop, so that as new frames are captured, any new stitching errors occurring in the video sequence are analyzed and corrected as the sequence progresses. These algorithms are suitable for multiscale cameras, a camera array technology proven to be capable of gigapixel snapshot and video imaging, to allow for real-time compensation of any registration or parallax errors.

  20. Multivariable control of the Space Shuttle Remote Manipulator System using linearization by state feedback. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Gettman, Chang-Ching LO

    1993-01-01

    This thesis develops and demonstrates an approach to nonlinear control system design using linearization by state feedback. The design provides improved transient response behavior allowing faster maneuvering of payloads by the SRMS. Modeling uncertainty is accounted for by using a second feedback loop designed around the feedback linearized dynamics. A classical feedback loop is developed to provide the easy implementation required for the relatively small on board computers. Feedback linearization also allows the use of higher bandwidth model based compensation in the outer loop, since it helps maintain stability in the presence of the nonlinearities typically neglected in model based designs.

  1. Feedbacks in Human-Landscape Systems

    NASA Astrophysics Data System (ADS)

    Chin, Anne; Florsheim, Joan L.; Wohl, Ellen; Collins, Brian D.

    2014-01-01

    This article identifies key questions and challenges for geomorphologists in investigating coupled feedbacks in human-landscape systems. While feedbacks occur in the absence of human influences, they are also altered by human activity. Feedbacks are a key element to understanding human-influenced geomorphic systems in ways that extend our traditional approach of considering humans as unidirectional drivers of change. Feedbacks have been increasingly identified in Earth-environmental systems, with studies of coupled human-natural systems emphasizing ecological phenomena in producing emerging concepts for social-ecological systems. Enormous gaps or uncertainties in knowledge remain with respect to understanding impact-feedback loops within geomorphic systems with significant human alterations, where the impacted geomorphic systems in turn affect humans. Geomorphology should play an important role in public policy by identifying the many diffuse and subtle feedbacks of both local- and global-scale processes. This role is urgent, while time may still be available to mitigate the impacts that limit the sustainability of human societies. Challenges for geomorphology include identification of the often weak feedbacks that occur over varied time and space scales ranging from geologic time to single isolated events and very short time periods, the lack of available data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, the varied tools and metrics needed to represent both physical and human processes, and the need to collaborate with social scientists with expertise in the human causes of geomorphic change, as well as the human responses to such change.

  2. Cardiac arrhythmias and degradation into chaotic behavior prevention using feedback control

    NASA Astrophysics Data System (ADS)

    Uzelac, Ilija; Sidorov, Veniamin; Wikswo, John; Gray, Richard

    2012-02-01

    During normal heart rhythm, cardiac cells behave as a set of oscillators with a distribution of phases but with the same frequency. The heart as a dynamical system in a phase space representation can be modeled as a set of oscillators that have closed overlapping orbits with the same period. These orbits are not stable and in the case of disruption of the cardiac rhythm, such as due to premature beats, the system will have a tendency to leave its periodic unstable orbits. If these orbits become attracted to phase singularities, their disruption may lead to chaotic behavior, which appears as a life-threating ventricular fibrillation. By using closed-loop feedback in the form of an adjustable defibrillation shock, any drift from orbits corresponding to the normal rhythm can be corrected by forcing the system to maintain its orbits. The delay through the feedback network coincides with the period of normal heart beats. To implement this approach we developed a 1 kW arbitrary waveform voltage-to-current converter with a 1 kHz bandwidth driven by a photodiode system that records an optical electrocardiogram and provides a feedback signal in real time. Our goal is to determine whether our novel method to defibrillate the heart will require much lower energies than are currently utilized in single shock defibrillators.

  3. Semiclassical spin-spin dynamics and feedback control in transport through a quantum dot

    NASA Astrophysics Data System (ADS)

    Mosshammer, Klemens; Brandes, Tobias

    2014-10-01

    We present a theory of magnetotransport through an electronic orbital, where the electron spin interacts with a (sufficiently) large external spin via an exchange interaction. Using a semiclassical approximation, we derive a set of equations of motions for the electron density matrix and the mean value of the external spin that turns out to be highly nonlinear. The dissipation via the electronic leads is implemented in terms of a quantum master equation that is combined with the nonlinear terms of the spin-spin interaction. With an anisotropic exchange coupling a variety of dynamics is generated, such as self-sustained oscillations with parametric resonances or even chaotic behavior. Within our theory we can integrate a Maxwell-demon-like closed-loop feedback scheme that is capable of transporting particles against an applied bias voltage and that can be used to implement a spin filter to generate spin-dependent oscillating currents of opposite directions.

  4. Building steady-state simulators via hierarchical feedback decomposition

    SciTech Connect

    Rouquette, N.

    1996-12-31

    In recent years, compositional modeling and self-explanatory simulation techniques have simplified the process of building dynamic simulators of physical systems. Building steady-state simulators is, conceptually, a simpler task consisting in solving a set algebraic equations. This simplicity hides delicate technical issues of convergence and search-space size due to the potentially large number of unknown parameters. We present an automated technique for reducing the dimensionality of the problem by (1) automatically identifying feedback loops (a generally NP-complete problem), (2) hierarchically decomposing the set of equations in terms of feedback loops, and (3) structuring a simulator where equations are solved either serially without search or in isolation within a feedback loop. This paper describes the key algorithms and the results of their implementation on building simulators for a two-phase evaporator loop system across multiple combinations of causal and non-causal approximations.

  5. Stability analysis and compensation of a boost regulator with two-loop control

    NASA Technical Reports Server (NTRS)

    Wester, G. W.

    1974-01-01

    A useful stability measure has been demonstrated by Wester (1973) for switching regulators with a single feedback loop by applying the Nyquist criterion to the approximate loop gain determined by a time-averaging technique. This approach is extended and applied to the characterization, stability analysis, and compensation design of a switching regulator with two-loop control. The role and relative significance of each control loop is clarified on the basis of a description of circuit operation, and the major and minor loops are identified. In view of the inapplicability of linear feedback theory, describing functions of the feedback loops and power stage are derived, using small-signal analysis. Several phenomena revealed from an analysis of the major loop gain are discussed.

  6. A Theory of Circular Organization and Negative Feedback: Defining Life in a Cybernetic Context

    NASA Astrophysics Data System (ADS)

    Tsokolov, Sergey

    2010-12-01

    All life today incorporates a variety of systems controlled by negative feedback loops and sometimes amplified by positive feedback loops. The first forms of life necessarily also required primitive versions of feedback, yet surprisingly little emphasis has been given to the question of how feedback emerged out of primarily chemical systems. One chemical system has been established that spontaneously develops autocatalytic feedback, the Belousov-Zhabotinsky (BZ) reaction. In this essay, I discuss the BZ reaction as a possible model for similar reactions that could have occurred under prebiotic Earth conditions. The main point is that the metabolism of contemporary life evolved from primitive homeostatic networks regulated by negative feedback. Because life could not exist in their absence, feedback loops should be included in definitions of life.

  7. Improving Low Voltage Ride Through Capability of Wind Generators Using Dynamic Voltage Restorer

    NASA Astrophysics Data System (ADS)

    Sivasankar, Gangatharan; Suresh Kumar, Velu

    2014-08-01

    The increasing wind power integration with power grid has forced the situation to improve the reliability of wind generators for stable operation. One important problem with induction generator based wind farm is its low ride through capability to the grid voltage disturbance. Any disturbance such as voltage dip may cause wind farm outages. Since wind power contribution is in predominant percentage, such outages may lead to stability problem. The proposed strategy is to use dynamic voltage controller (DVR) to compensate the voltage disturbance. The DVR provides the wind generator the ability to remain connected in grid and improve the reliability. The voltage dips due to symmetrical and unsymmetrical faults are considered for analysis. The vector control scheme is employed for fault compensation which uses software phase locked loop scheme and park dq0 transformation technique. Extensive simulation results are included to illustrate the control and operation of DVR.

  8. Converter Circuit «Voltage-Voltage» Investigation for Power Calibrator

    NASA Astrophysics Data System (ADS)

    Fomichev, Yu M.; Silushkin, S. V.; Mylnikova, T. S.

    2016-01-01

    The paper presents possible circuits to construct a voltage-voltage converter for the calibrator of fictitious power. The problems of circuit solutions were experimentally identified, and the ways of their elimination were found. One of the main problems of convectors is to provide small harmonic distortions and additional phase shift. The use of deep negative instantaneous value feedback helps to provide the desired level of nonlinear distortions and to reduce the phase shift. Corrective circuits are used to ensure the stability of the transducer at greater depths of the feedback; the half-period average value or rms value feedback is used to ensure the stability and accuracy of conversion. However, the accuracy of the power calibrator can be upgraded and its work for various types of loads can be ensured by means of application follower circuit with modern electronic components which are also discussed in the paper.

  9. Adaptive feed-forward loop connection based on error signal

    NASA Astrophysics Data System (ADS)

    Hidaka, Koichi

    2005-12-01

    In this paper, we investigate effect of changing the connection of feed-forward loop based on error signal. Our motivation of this work is solution to progress of human skill. For the skill model, we study a human simple action such as arm motion. Many models that describe the human arm dynamics have been proposed in recent year. While one type does not need an inverse model of human dynamics, the system based on the model does not include feed-forward loop. On the other hand, another type model has a feed-forward loop and feedback loop systems. This type assumes feed-forward element includes an internal model by repeating action or training and this loop progress our skill. Then we usually have to exercise to get a good performance. This says that we design the internal motion model by training and we move on prediction for motion. Under the assumption, Kawato model is well known. The model proposed that learning of feed-forward element is promoted in brain so that the error of feedback loop decreases. Furthermore, we assume the connections in feedback loop and feed-forward loop are changed. We show numerical simulations and consider that the position error given by our vision changes the skill element and we confirm that the position error is the one of the estimate function for the improvement in our skill.

  10. An intensity ratio of interlocking loops determines circadian period length

    PubMed Central

    Yan, Jie; Shi, Guangsen; Zhang, Zhihui; Wu, Xi; Liu, Zhiwei; Xing, Lijuan; Qu, Zhipeng; Dong, Zhen; Yang, Ling; Xu, Ying

    2014-01-01

    Circadian clocks allow organisms to orchestrate the daily rhythms in physiology and behaviors, and disruption of circadian rhythmicity can profoundly affect fitness. The mammalian circadian oscillator consists of a negative primary feedback loop and is associated with some auxiliary loops. This raises the questions of how these interlocking loops coordinate to regulate the period and maintain its robustness. Here, we focused on the REV-ERB?/Cry1 auxiliary loop, consisting of Rev-Erb?/ROR-binding elements (RORE) mediated Cry1 transcription, coordinates with the negative primary feedback loop to modulate the mammalian circadian period. The silicon simulation revealed an unexpected rule: the intensity ratio of the primary loop to the auxiliary loop is inversely related to the period length, even when post-translational feedback is fixed. Then we measured the mRNA levels from two loops in 10-mutant mice and observed the similar monotonic relationship. Additionally, our simulation and the experimental results in human osteosarcoma cells suggest that a coupling effect between the numerator and denominator of this intensity ratio ensures the robustness of circadian period and, therefore, provides an efficient means of correcting circadian disorders. This ratio rule highlights the contribution of the transcriptional architecture to the period dynamics and might be helpful in the construction of synthetic oscillators. PMID:25122753

  11. Delayed feedback of sampled higher derivatives.

    PubMed

    Insperger, Tamas; Stepan, Gabor; Turi, Janos

    2010-01-28

    Systems where the present rate of change of the state depends on the past values of the higher rates of change of the state are described by so-called advanced functional differential equations (AFDEs). In an AFDE, the highest derivative of the state-space coordinate appears with delayed argument only. The corresponding linearized equations are always unstable with infinitely many unstable poles, and are rarely related to practical applications due to their inherently implicit nature. In this paper, one of the simplest AFDEs, a linear scalar first-order system, is considered with the delayed feedback of the second derivative of the state in the presence of sampling in the feedback loop (i.e. in the case of digital control). It is shown that sampling of the feedback may stabilize the originally infinitely unstable system for certain parameter combinations. The result explains the stable behaviour of certain dynamical systems with feedback delay in the highest derivative. PMID:20008412

  12. Novel distributed feedback lightwave circuit elements

    NASA Astrophysics Data System (ADS)

    Daǧ, Ceren B.; Anil, Mehmet A.; Serpengüzel, Ali

    2015-02-01

    The devices that are variations of inter-and intracoupled meandering optical waveguides are proposed as the lightwave circuit elements that exhibit distributed feedback. A preliminary transfer matrix method analysis is applied in frequency domain, taking the coupling purely directional and with constant coefficient on geometrically symmetric and anti-symmetric devices. The meandering loop mirror is the building block of all meandering waveguide based lightwave circuit elements. The simplest uncoupled meandering distributed feedback structure exhibits Rabi splitting in the transmittance spectrum. The symmetric and antisymmetric coupled meandering distributed feedback geometries can be utilized as band-pass, Fano, or Lorentzian filters or Rabi splitters. Meandering waveguide distributed feedback structures with a variety of spectral responses can be designed for a variety of lightwave circuit element functions and can be implemented with generality due to the analytic approach taken.

  13. HIGH VOLTAGE GENERATOR

    DOEpatents

    Zito, G.V.

    1959-04-21

    This patent relates to high voltage supply circuits adapted for providing operating voltages for GeigerMueller counter tubes, and is especially directed to an arrangement for maintaining uniform voltage under changing conditions of operation. In the usual power supply arrangement for counter tubes the counter voltage is taken from across the power supply output capacitor. If the count rate exceeds the current delivering capaciiy of the capacitor, the capacitor voltage will drop, decreasing the counter voltage. The present invention provides a multivibrator which has its output voltage controlled by a signal proportional to the counting rate. As the counting rate increases beyond the current delivering capacity of the capacitor, the rectified voltage output from the multivibrator is increased to maintain uniform counter voltage.

  14. Transient Voltage Recorder

    NASA Astrophysics Data System (ADS)

    Medelius, Pedro J.; Simpson, Howard J.

    2002-09-01

    A voltage transient recorder can detect lightning induced transient voltages. The recorder detects a lightning induced transient voltage and adjusts input amplifiers to accurately record transient voltage magnitudes. The recorder stores voltage data from numerous monitored channels, or devices. The data is time stamped and can be output in real time, or stored for later retrieval. The transient recorder, in one embodiment, includes an analog-to-digital converter and a voltage threshold detector. When an input voltage exceeds a pre-determined voltage threshold, the recorder stores the incoming voltage magnitude and time of arrival. The recorder also determines if its input amplifier circuits clip the incoming signal or if the incoming signal is too low. If the input data is clipped or too low, the recorder adjusts the gain of the amplifier circuits to accurately acquire subsequent components of the lightning induced transients.

  15. Closed orbit feedback with digital signal processing

    SciTech Connect

    Chung, Y.; Kirchman, J.; Lenkszus, F.

    1994-08-01

    The closed orbit feedback experiment conducted on the SPEAR using the singular value decomposition (SVD) technique and digital signal processing (DSP) is presented. The beam response matrix, defined as beam motion at beam position monitor (BPM) locations per unit kick by corrector magnets, was measured and then analyzed using SVD. Ten BPMs, sixteen correctors, and the eight largest SVD eigenvalues were used for closed orbit correction. The maximum sampling frequency for the closed loop feedback was measured at 37 Hz. Using the proportional and integral (PI) control algorithm with the gains Kp = 3 and K{sub I} = 0.05 and the open-loop bandwidth corresponding to 1% of the sampling frequency, a correction bandwidth ({minus}3 dB) of approximately 0.8 Hz was achieved. Time domain measurements showed that the response time of the closed loop feedback system for 1/e decay was approximately 0.25 second. This result implies {approximately} 100 Hz correction bandwidth for the planned beam position feedback system for the Advanced Photon Source storage ring with the projected 4-kHz sampling frequency.

  16. Particle deformation induced by AFM tapping under different setpoint voltages

    NASA Astrophysics Data System (ADS)

    Wu, Chung-Lin; Farkas, Natalia; Dagata, John A.; He, Bo-Ching; Fu, Wei-En

    2014-09-01

    The measured height of polystyrene nanoparticles varies with setpoint voltage during atomic force microscopy (AFM) tapping-mode imaging. Nanoparticle height was strongly influenced by the magnitude of the deformation caused by the AFM tapping forces, which was determined by the setpoint voltage. This influence quantity was studied by controlling the operational AFM setpoint voltage. A test sample consisting of well-dispersed 60-nm polystyrene and gold nanoparticles co-adsorbed on poly-l-lysine-coated mica was studied in this research. Gold nanoparticles have not only better mechanical property than polystyrene nanoparticles, but also obvious facets in AFM phase image. By using this sample of mixed nanoparticles, it allows us to confirm that the deformation resulted from the effect of setpoint voltage, not noise. In tapping mode, the deformation of polystyrene nanoparticles increased with decreasing setpoint voltage. Similar behavior was observed with both open loop and closed loop AFM instruments.

  17. The preprocessed doacross loop

    NASA Technical Reports Server (NTRS)

    Saltz, Joel H.; Mirchandaney, Ravi

    1990-01-01

    Dependencies between loop iterations cannot always be characterized during program compilation. Doacross loops typically make use of a-priori knowledge of inter-iteration dependencies to carry out required synchronizations. A type of doacross loop is proposed that allows the scheduling of iterations of a loop among processors without advance knowledge of inter-iteration dependencies. The method proposed for loop iterations requires that parallelizable preprocessing and postprocessing steps be carried out during program execution.

  18. Student Engagement with Feedback

    ERIC Educational Resources Information Center

    Scott, Jon; Shields, Cathy; Gardner, James; Hancock, Alysoun; Nutt, Alex

    2011-01-01

    This report considers Biological Sciences students' perceptions of feedback, compared with those of the University as a whole, this includes what forms of feedback were considered most useful and how feedback used. Compared with data from previous studies, Biological Sciences students gave much greater recognition to oral feedback, placing it on a…

  19. Monolithic amplifier with stable, high resistance feedback element and method for fabricating the same

    DOEpatents

    O'Connor, Paul

    1998-08-11

    A monolithic amplifier includes a stable, high resistance feedback circuit and a dynamic bias circuit. The dynamic bias circuit is formed with active elements matched to those in the amplifier and feedback circuit to compensate for variations in the operating and threshold voltages thereby maintaining a stable resistance in the feedback circuit.

  20. Monolithic amplifier with stable, high resistance feedback element and method for fabricating the same

    DOEpatents

    O`Connor, P.

    1998-08-11

    A monolithic amplifier includes a stable, high resistance feedback circuit and a dynamic bias circuit. The dynamic bias circuit is formed with active elements matched to those in the amplifier and feedback circuit to compensate for variations in the operating and threshold voltages thereby maintaining a stable resistance in the feedback circuit. 11 figs.

  1. Quantum feedback experiments with atoms and cavities

    NASA Astrophysics Data System (ADS)

    Raimond, Jean-Michel

    2012-06-01

    Quantum feedback transposes the usual feedback loop concept into the quantum world. A measurement performed on the system by the sensor is used by a controller to infer the system's state and to steer it towards the target by the action of the actuator. This scheme has to face a fundamental difficulty, since the measurement changes the system's state. This back-action makes quantum feedback algorithms more complex than their classical counterparts. We report the first successful operation of a repeated quantum feedback loop [1]. It prepares photon number states (from 0 to 4 photons) on-demand in a superconducting microwave cavity and subsequently reverses the effect of decoherence-induced quantum jumps. The quantum sensors are circular Rydberg atoms, performing a Quantum Non Demolition (QND) measurement of the cavity field. Information they provide is used by the controller (real-time computer) to estimate the field state. The controller determines the amplitude of a coherent displacement leading the cavity closer to the target This displacement is performed by a microwave source acting as the actuator. Iterations of this loop rapidly drive the cavity towards the prescribed target. When it is reached, the actuator idles. It resumes operation when atomic detections indicate that a photon has been lost, or that a thermal photon has appeared. The feedback compensates for these quantum jumps and rapidly restores the field in the target state. In a variant of the experiment, we use quantum actuators, resonant atoms that feed photons back in the cavity when they get lost. This more efficient scheme allows us to stabilize higher photon numbers. These experiments are a first step towards the use of quantum feedback to protect fragile quantum resources. We also consider an alternative route towards state protection based on reservoir engineering [2]. [4pt] [1] C. Sayrin et al. Nature (London) 477, 73 (2011)[0pt] [2] A. Sarlette et al. Phys. Rev. Lett. 107, 010402 (2011)

  2. Automated setup for magnetic hysteresis characterization based on a voltage controlled current source with 500 kHz full power bandwidth and 10 A peak-to-peak current

    SciTech Connect

    Calabrese, G.; Capineri, L.; Granato, M.; Frattini, G.

    2015-04-15

    This paper describes the design of a system for the characterization of magnetic hysteresis behavior in soft ferrite magnetic cores. The proposed setup can test magnetic materials exciting them with controlled arbitrary magnetic field waveforms, including the capability of providing a DC bias, in a frequency bandwidth up to 500 kHz, with voltages up to 32 V peak-to-peak, and currents up to 10 A peak-to-peak. In order to have an accurate control of the magnetic field waveform, the system is based on a voltage controlled current source. The electronic design is described focusing on closed loop feedback stabilization and passive components choice. The system has real-time hysteretic loop acquisition and visualization. The comparisons between measured hysteresis loops of sample magnetic materials and datasheet available ones are shown. Results showing frequency and thermal behavior of the hysteresis of a test sample prove the system capabilities. Moreover, the B-H loops obtained with a multiple waveforms excitation signal, including DC bias, are reported. The proposal is a low-cost and replicable solution for hysteresis characterization of magnetic materials used in power electronics.

  3. Automatic voltage imbalance detector

    DOEpatents

    Bobbett, Ronald E.; McCormick, J. Byron; Kerwin, William J.

    1984-01-01

    A device for indicating and preventing damage to voltage cells such as galvanic cells and fuel cells connected in series by detecting sequential voltages and comparing these voltages to adjacent voltage cells. The device is implemented by using operational amplifiers and switching circuitry is provided by transistors. The device can be utilized in battery powered electric vehicles to prevent galvanic cell damage and also in series connected fuel cells to prevent fuel cell damage.

  4. Enhancement of field squeezing using coherent feedback

    SciTech Connect

    Gough, J. E.; Wildfeuer, S.

    2009-10-15

    The theory of quantum feedback networks has recently been developed with the aim of showing how quantum input-output components may be connected together so as to control, stabilize, or enhance the performance of one of the subcomponents. In this paper, we show how the degree to which an idealized component (a degenerate parametric amplifier in the strong-coupling regime) can squeeze input fields may be enhanced by placing the component in loop in a simple feedback mechanism involving a beam splitter. We study the spectral properties of output fields, placing particular emphasis on the elastic and inelastic components of the power density.

  5. Mixed voltage VLSI design

    NASA Technical Reports Server (NTRS)

    Panwar, Ramesh; Rennels, David; Alkalaj, Leon

    1993-01-01

    A technique for minimizing the power dissipated in a Very Large Scale Integration (VLSI) chip by lowering the operating voltage without any significant penalty in the chip throughput even though low voltage operation results in slower circuits. Since the overall throughput of a VLSI chip depends on the speed of the critical path(s) in the chip, it may be possible to sustain the throughput rates attained at higher voltages by operating the circuits in the critical path(s) with a high voltage while operating the other circuits with a lower voltage to minimize the power dissipation. The interface between the gates which operate at different voltages is crucial for low power dissipation since the interface may possibly have high static current dissipation thus negating the gains of the low voltage operation. The design of a voltage level translator which does the interface between the low voltage and high voltage circuits without any significant static dissipation is presented. Then, the results of the mixed voltage design using a greedy algorithm on three chips for various operating voltages are presented.

  6. Inverse spin Hall effect in a closed loop circuit

    SciTech Connect

    Omori, Y.; Auvray, F.; Wakamura, T.; Niimi, Y.; Fert, A.

    2014-06-16

    We present measurements of inverse spin Hall effects (ISHEs), in which the conversion of a spin current into a charge current via the ISHE is detected not as a voltage in a standard open circuit but directly as the charge current generated in a closed loop. The method is applied to the ISHEs of Bi-doped Cu and Pt. The derived expression of ISHE for the loop structure can relate the charge current flowing into the loop to the spin Hall angle of the SHE material and the resistance of the loop.

  7. Adaptive Inner-Loop Rover Control

    NASA Technical Reports Server (NTRS)

    Kulkarni, Nilesh; Ippolito, Corey; Krishnakumar, Kalmanje; Al-Ali, Khalid M.

    2006-01-01

    Adaptive control technology is developed for the inner-loop speed and steering control of the MAX Rover. MAX, a CMU developed rover, is a compact low-cost 4-wheel drive, 4-wheel steer (double Ackerman), high-clearance agile durable chassis, outfitted with sensors and electronics that make it ideally suited for supporting research relevant to intelligent teleoperation and as a low-cost autonomous robotic test bed and appliance. The design consists of a feedback linearization based controller with a proportional - integral (PI) feedback that is augmented by an online adaptive neural network. The adaptation law has guaranteed stability properties for safe operation. The control design is retrofit in nature so that it fits inside the outer-loop path planning algorithms. Successful hardware implementation of the controller is illustrated for several scenarios consisting of actuator failures and modeling errors in the nominal design.

  8. Probabilistic models for feedback systems.

    SciTech Connect

    Grace, Matthew D.; Boggs, Paul T.

    2011-02-01

    In previous work, we developed a Bayesian-based methodology to analyze the reliability of hierarchical systems. The output of the procedure is a statistical distribution of the reliability, thus allowing many questions to be answered. The principal advantage of the approach is that along with an estimate of the reliability, we also can provide statements of confidence in the results. The model is quite general in that it allows general representations of all of the distributions involved, it incorporates prior knowledge into the models, it allows errors in the 'engineered' nodes of a system to be determined by the data, and leads to the ability to determine optimal testing strategies. In this report, we provide the preliminary steps necessary to extend this approach to systems with feedback. Feedback is an essential component of 'complexity' and provides interesting challenges in modeling the time-dependent action of a feedback loop. We provide a mechanism for doing this and analyze a simple case. We then consider some extensions to more interesting examples with local control affecting the entire system. Finally, a discussion of the status of the research is also included.

  9. Convection and the Soil-Moisture Precipitation Feedback

    NASA Astrophysics Data System (ADS)

    Schar, C.; Froidevaux, P.; Keller, M.; Schlemmer, L.; Langhans, W.; Schmidli, J.

    2014-12-01

    The soil moisture - precipitation (SMP) feedback is of key importance for climate and climate change. A positive SMP feedback tends to amplify the hydrological response to external forcings (and thereby fosters precipitation and drought extremes), while a negative SMP feedback tends to moderate the influence of external forcings (and thereby stabilizes the hydrological cycle). The sign of the SMP feedback is poorly constrained by the current literature. Theoretical, modeling and observational studies partly disagree, and have suggested both negative and positive feedback loops. Can wet soil anomalies indeed result in either an increase or a decrease of precipitation (positive or negative SMP feedback, respectively)? Here we investigate the local SMP feedback using real-case and idealized convection-resolving simulations. An idealized simulation strategy is developed, which is able to replicate both signs of the feedback loop, depending on the environmental parameters. The mechanism relies on horizontal soil moisture variations, which may develop and intensify spontaneously. The positive expression of the feedback is associated with the initiation of convection over dry soil patches, but the convective cells then propagate over wet patches, where they strengthen and preferentially precipitate. The negative feedback may occur when the wind profile is too weak to support the propagation of convective features from dry to wet areas. Precipitation is then generally weaker and falls preferentially over dry patches. The results highlight the role of the mid-tropospheric flow in determining the sign of the feedback. A key element of the positive feedback is the exploitation of both low convective inhibition (CIN) over dry patches (for the initiation of convection), and high CAPE over wet patches (for the generation of precipitation). The results of this study will also be discussed in relation to climate change scenarios that exhibit large biases in surface temperature and interannual variability over mid-latitude summer climates, both over Europe and North America. It is argued that parameterized convection may contribute towards such biases by overemphasizing a positive SMP feedback.

  10. RF Voltage Measurements on ICRF Antennas

    NASA Astrophysics Data System (ADS)

    Bell, G. L.; Goulding, R. H.; Hoffman, D. J.; Wilgen, J. B.; Zhang, H. M.; Ryan, P. M.; Syed, G. M. S.; Kaye, A. S.

    1996-11-01

    Particle and heat flux on the plasma facing surfaces of high-power RF antennas used in fusion devices can result in damage to the antenna structures. High impedance capacitive probe measurements of the RF voltages on Faraday shields of several loop antennas indicate that voltages as high as 30% of the drive voltage can exist for 0/0 phasing (D.J. Hoffman, et al., AIP Conf. Proc. 355), 368 (Palm Spgs., CA, 1995).. These voltages can contribute to increased energy deposition on the antenna owing to increased RF sheath voltages. We report on continued efforts to understand the source and to control these RF voltages. E and B field distributions have been measured on the mock-up of the JET A2 antenna using standard B-dot probes and novel E-field probes positioned with a new automated scanning system. These data are compared with calculated fields from 3-D antenna models. The measurements demonstrate the dependency of the surface E-fields on the phasing of the strap currents and show the charge accumulation at the antenna top and bottom predicted by the models.

  11. Feedbacks in human-landscape systems

    NASA Astrophysics Data System (ADS)

    Chin, Anne

    2015-04-01

    As human interactions with Earth systems intensify in the "Anthropocene", understanding the complex relationships among human activity, landscape change, and societal responses to those changes is increasingly important. Interdisciplinary research centered on the theme of "feedbacks" in human-landscape systems serves as a promising focus for unraveling these interactions. Deciphering interacting human-landscape feedbacks extends our traditional approach of considering humans as unidirectional drivers of change. Enormous challenges exist, however, in quantifying impact-feedback loops in landscapes with significant human alterations. This paper illustrates an example of human-landscape interactions following a wildfire in Colorado (USA) that elicited feedback responses. After the 2012 Waldo Canyon Fire, concerns for heightened flood potential and debris flows associated with post-fire hydrologic changes prompted local landowners to construct tall fences at the base of a burned watershed. These actions changed the sediment transport regime and promoted further landscape change and human responses in a positive feedback cycle. The interactions ultimately increase flood and sediment hazards, rather than dampening the effects of fire. A simple agent-based model, capable of integrating social and hydro-geomorphological data, demonstrates how such interacting impacts and feedbacks could be simulated. Challenges for fully capturing human-landscape feedback interactions include the identification of diffuse and subtle feedbacks at a range of scales, the availability of data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, and the varied metrics and data needed to represent both the physical and human systems. By collaborating with social scientists with expertise in the human causes of landscape change, as well as the human responses to those changes, geoscientists could more fully recognize and anticipate the coupled human-landscape interactions that will drive the evolution of Earth systems into the future.

  12. Feedback on Feedback--Does It Work?

    ERIC Educational Resources Information Center

    Speicher, Oranna; Stollhans, Sascha

    2015-01-01

    It is well documented that providing assessment feedback through the medium of screencasts is favourably received by students and encourages deeper engagement with the feedback given by the language teacher (inter alia Abdous & Yoshimura, 2010; Brick & Holmes, 2008; Cann, 2007; Stannard, 2007). In this short paper we will report the…

  13. Measurement of rf voltages on the plasma-touching surfaces of ICRF antennas

    SciTech Connect

    Hoffman, D.J.; Baity, F.W.; Bell, G.L.; Bigelow, T.S.; Caughman, J.B.O.; Goulding, R.H.; Haste, G.R.; Ryan, P.M.; Zhang, H.

    1995-09-01

    Measurements of the rf voltages on Faraday shields and protection bumpers have been made for several loop antennas, including the mock-up antenna and Al for JET, the original antenna for Tore Supra, the present ASDEX-U antenna, and the folded waveguide. The loop antennas show voltages that scale to {approx}12 kV for a maximum input voltage of 30 kV with 0/0 phasing. The voltages are dramatically reduced for 0/{pi} phasing. These voltages are significant in that they can substantially increase the rf sheath potential beyond the levels associated with the simple electromagnetic field linkage from the current straps that results in plasma heating. In this paper, we investigate and measure the source of these voltages, their scaling with antenna impedance, and the differences between the loop arrays.

  14. Measurement of rf voltages on the plasma-touching surfaces of ICRF antennas

    SciTech Connect

    Hoffman, D.J.; Baity, F.W.; Bell, G.L.; Bigelow, T.S.; Caughman, J.B.; Goulding, R.H.; Haste, G.R.; Ryan, P.M.; Zhang, H.

    1996-02-01

    Measurements of the rf voltages on Faraday shields and protection bumpers have been made for several loop antennas, including the mock-up antenna and A1 for JET, the original antenna for Tore Supra, the present ASDEX-U antenna, and the folded waveguide. The loop antennas show voltages that scale to {approx_equal}12 kV for a maximum input voltage of 30 kV with 0/0 phasing. The voltages are dramatically reduced for 0/{pi} phasing. These voltages are significant in that they can substantially increase the rf sheath potential beyond the levels associated with the simple electromagnetic field linkage from the current straps that results in plasma heating. In this paper, we investigate and measure the source of these voltages, their scaling with antenna impedance, and the differences between the loop arrays. {copyright} {ital 1996 American Institute of Physics.}

  15. Measurement of rf voltages on the plasma-touching surfaces of ICRF antennas

    NASA Astrophysics Data System (ADS)

    Hoffman, D. J.; Baity, F. W.; Bell, G. L.; Bigelow, T. S.; Caughman, J. B. O.; Goulding, R. H.; Haste, G. R.; Ryan, P. M.; Zhang, H.

    1996-02-01

    Measurements of the rf voltages on Faraday shields and protection bumpers have been made for several loop antennas, including the mock-up antenna and A1 for JET, the original antenna for Tore Supra, the present ASDEX-U antenna, and the folded waveguide. The loop antennas show voltages that scale to ≊12 kV for a maximum input voltage of 30 kV with 0/0 phasing. The voltages are dramatically reduced for 0/π phasing. These voltages are significant in that they can substantially increase the rf sheath potential beyond the levels associated with the simple electromagnetic field linkage from the current straps that results in plasma heating. In this paper, we investigate and measure the source of these voltages, their scaling with antenna impedance, and the differences between the loop arrays.

  16. Internal and external feedback circuits for skilled forelimb movement

    PubMed Central

    Azim, Eiman; Fink, Andrew J.P.; Jessell, Thomas M.

    2015-01-01

    Skilled motor behavior emerges from interactions between efferent neural pathways that induce muscle contraction and feedback systems that report and refine movement. Two broad classes of feedback projections modify motor output, one from the periphery and a second that originates within the central nervous system. The mechanisms through which these pathways influence movement remain poorly understood, however. Here we discuss recent studies that delineate spinal circuitry that binds external and internal feedback pathways to forelimb motor behavior. A spinal presynaptic inhibitory circuit regulates the strength of external feedback, promoting limb stability during goal-directed reaching. A distinct excitatory propriospinal circuit conveys copies of motor commands to the cerebellum, establishing an internal feedback loop that rapidly modulates forelimb motor output. The behavioral consequences of manipulating these two circuits reveal distinct controls on motor performance, and provide an initial insight into feedback strategies that underlie skilled forelimb movement. PMID:25699987

  17. Feedback control of the bending response of ionic polymer-metal composite actuators

    NASA Astrophysics Data System (ADS)

    Mallavarapu, Kiran; Newbury, Kenneth M.; Leo, Donald J.

    2001-07-01

    Many physical models of ionic polymer have been developed. However, these models are not suitable for use in the design of control systems for Ionic Polymer-Metal Composite(IPMC) actuators. In this paper an empirical model of IPMC is developed and used for closed-loop control. The empirical model is developed by measuring the step response of 20mm x 10mm IPMC actuator in a cantilever configuration . Using this empirical model, a compensator was designed using a linear observer-estimator in state space. Since the IPMC has a slow time constant, it cannot be used to actuate high frequency signals. The design objectives were to constrain the control voltage to less than 2 Volts and minimize the settling time by using feedback control. The controller was designed using Linear Quadratic Regulator(LQR) techniques which reduced the number of design parameters to one variable. This LQR parameter was varied and simulations were performed which showed settling time of 0.15 seconds for closed-loop as compared to a open-loop settling time of 7 seconds. The maximum control input varied from 1.1 Volts to 2.5 Volts for the simulations depending on the LQR parameter. The controller was later used in experimentation to check simulations. Results obtained were consistent to a high degree. Closed-loop settling time was observed to be 0.95 seconds and the maximum control input was less than 2.3 Volts. Experimentation also revealed a high overshoot and oscillations before settling which occurred due to the excitation of IPMC at its natural frequency. Thus, need to include the higher frequency dynamics was highlighted.

  18. Development of a design tool for closed-loop digital vibrometer.

    PubMed

    Melchionni, Dario; Magnani, Alessandro; Pesatori, Alessandro; Norgia, Michele

    2015-11-10

    The closed-loop technique has been demonstrated as a possible configuration to design a vibrometer based upon self-mixing interferometry. The electronic feedback loop allows a better linearity while extending the linearity range of a self-mixing interferometer. A deep analysis of the feedback loop is carried out in order to improve stability and performance through a digital approach. This work describes first the simulation of the closed-loop vibrometer, and then the performance obtained through its implementation on an FPGA based prototype. PMID:26560797

  19. Generalized modal analysis for closed-loop piezoelectric devices

    NASA Astrophysics Data System (ADS)

    Giraud-Audine, Christophe; Giraud, Frédéric; Amberg, Michel; Lemaire-Semail, Betty

    2015-08-01

    Stress in a piezoelectric material can be controlled by imposing an electrical field. Thanks to feedback, this electrical field can be a function of some strain-related measurement so as to confer on the piezoelectric device a closed-loop macroscopic behaviour. In this paper we address the modelling of such a system by extending the modal decomposition methods to account for the closed loop. To do so, the boundary conditions are modified to include the electrical feedback circuit, hence allowing a closed-loop modal analysis. A case study is used to illustrate the theory and to validate it. The main advantage of the method is that design issues such as the coupling factor of the device and closed-loop stability are simultaneously captured.

  20. Closed-Loop Optogenetic Brain Interface.

    PubMed

    Pashaie, Ramin; Baumgartner, Ryan; Richner, Thomas J; Brodnick, Sarah K; Azimipour, Mehdi; Eliceiri, Kevin W; Williams, Justin C

    2015-10-01

    This paper presents a new approach for implementation of closed-loop brain-machine interface algorithms by combining optogenetic neural stimulation with electrocorticography and fluorescence microscopy. We used a new generation of microfabricated electrocorticography (micro-ECoG) devices in which electrode arrays are embedded within an optically transparent biocompatible substrate that provides optical access to the brain tissue during electrophysiology recording. An optical setup was designed capable of projecting arbitrary patterns of light for optogenetic stimulation and performing fluorescence microscopy through the implant. For realization of a closed-loop system using this platform, the feedback can be taken from electrophysiology data or fluorescence imaging. In the closed-loop systems discussed in this paper, the feedback signal was taken from the micro-ECoG. In these algorithms, the electrophysiology data are continuously transferred to a computer and compared with some predefined spatial-temporal patterns of neural activity. The computer which processes the data also readjusts the duration and distribution of optogenetic stimulating pulses to minimize the difference between the recorded activity and the predefined set points so that after a limited period of transient response the recorded activity follows the set points. Details of the system design and implementation of typical closed-loop paradigms are discussed in this paper. PMID:26011877