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Sample records for voltage feedback loop

  1. Feedback loop compensates for rectifier nonlinearity

    NASA Technical Reports Server (NTRS)

    1966-01-01

    Signal processing circuit with two negative feedback loops rectifies two sinusoidal signals which are 180 degrees out of phase and produces a single full-wave rectified output signal. Each feedback loop incorporates a feedback rectifier to compensate for the nonlinearity of the circuit.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. An adaptive phase alignment algorithm for cartesian feedback loops

    NASA Astrophysics Data System (ADS)

    Gimeno-Martin, A.; Pardo-Martin, J.; Ortega-Gonzalez, F.

    2010-01-01

    An adaptive algorithm to correct phase misalignments in Cartesian feedback linearization loops for power amplifiers has been presented. It yields an error smaller than 0.035 rad between forward and feedback loop signals once convergence is reached. Because this algorithm enables a feedback system to process forward and feedback samples belonging to almost the same algorithm iteration, it is suitable to improve the performance not only of power amplifiers but also any other digital feedback system for communications systems and circuits such as all digital phase locked loops. Synchronizing forward and feedback paths of Cartesian feedback loops takes a small period of time after the system starts up. The phase alignment algorithm needs to converge before the feedback Cartesian loop can start its ideal behavior. However, once the steady state is reached, both paths can be considered synchronized, and the Cartesian feedback loop will only depend on the loop parameters (open-loop gain, loop bandwidth, etc.). It means that the linearization process will also depend only on these parameters since the misalignment effect disappears. Therefore, this algorithm relieves the power amplifier linearizer circuit design of any task required for solving phase misalignment effects inherent to Cartesian feedback systems. Furthermore, when a feedback Cartesian loop has to be designed, the designer can consider that forward and feedback paths are synchronized, since the phase alignment algorithm will do this task. This will reduce the simulation complexity. Then, all efforts are applied to determining the suitable loop parameters that will make the linearization process more efficient.

  7. Loop-voltage tomography in tokamaks using transient synchrotron radiation

    SciTech Connect

    Fisch, N.J.; Kritz, A.H. . Plasma Physics Lab.; Hunter Coll., New York, NY . Dept. of Physics)

    1989-07-01

    The loop voltage in tokamaks is particularly difficult to measure anywhere but at the plasma periphery. A brief, deliberate, perturbation of hot plasma electrons, however, produces a transient radiation response that is sensitive to this voltage. We investigate how such a radiation response can be used to diagnose the loop voltage. 24 refs., 6 figs.

  8. 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…

  9. 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.

  10. 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.

  11. Interaction between beam control and rf feedback loops for high Q cavities an heavy beam loading. Revision A

    SciTech Connect

    Mestha, L.K.; Kwan, C.M.; Yeung, K.S.

    1994-04-01

    An open-loop state space model of all the major low-level rf feedback control loops is derived. The model has control and state variables for fast-cycling machines to apply modern multivariable feedback techniques. A condition is derived to know when exactly we can cross the boundaries between time-varying and time-invariant approaches for a fast-cycling machine like the Low Energy Booster (LEB). The conditions are dependent on the Q of the cavity and the rate at which the frequency changes with time. Apart from capturing the time-variant characteristics, the errors in the magnetic field are accounted in the model to study the effects on synchronization with the Medium Energy Booster (MEB). The control model is useful to study the effects on beam control due to heavy beam loading at high intensities, voltage transients just after injection especially due to time-varying voltages, instability thresholds created by the cavity tuning feedback system, cross coupling between feedback loops with and without direct rf feedback etc. As a special case we have shown that the model agrees with the well known Pedersen model derived for the CERN PS booster. As an application of the model we undertook a detailed study of the cross coupling between the loops by considering all of them at once for varying time, Q and beam intensities. A discussion of the method to identify the coupling is shown. At the end a summary of the identified loop interactions is presented.

  12. 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.

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

    NASA Astrophysics Data System (ADS)

    Tiwari, Abhinav; Igoshin, Oleg A.

    2012-10-01

    Biochemical regulatory networks governing diverse cellular processes such as stress-response, differentiation and cell cycle often contain coupled feedback loops. We aim at understanding 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 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 the addition of a positive feedback to a bistable network increases the robustness of its bistability range, whereas the 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.

  14. 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

  15. Feedback loop process for controlling inertial cavitation: experimental evidence

    NASA Astrophysics Data System (ADS)

    Inserra, Claude; Sabraoui, Abbas; Reslan, Lina; Bera, Jean-Christophe; Gilles, Bruno; Mestas, Jean-Louis

    2011-09-01

    Applications involving cavitation mechanisms, such as sonoporation, are irreproducible in the case of a fixed-intensity sonication, due to the non-stationary behavior of cavitation. We then propose to work at a fixed-cavitation level instead of under fixed-intensity sonication conditions. For this purpose a regulated cavitation generator has been developed in a stationary wave field configuration, which allows regulation of the cavitation level during sonication by modulating the applied acoustic intensity with a feedback loop based on acoustic cavitation measurements. The cavitation level indicator was quantified by the broadband spectrum noise level relative to inertial cavitation events. This generated inertial cavitation was characterized by both acoustic and chemical measurements, quantifying hydroxyl radicals produced by water sonolysis. While the cavitation level is obtained with a 40% standard deviation for fixed applied acoustic intensities in the range [0.01 3.44] W/cm2, the regulated generator reproduces the cavitation level with a standard deviation of 3%. The results show that the hydroxyl radical production is better correlated with the cavitation level setting than with the applied acoustic intensity, highlighting the fact that broadband noise is a good indicator of inertial cavitation, with greatest interest for cavitation monitoring. In summary, the regulated device generates a cavitation level that is reproducible, repeatable and stable in time. This system produces reproducible effects that allow consideration of biological applications such as sonoporation to be independent of the experimental ultrasound device, as confirmed by transfection efficiency and cell cytotoxicity studies. Thus, this feedback loop process presents interesting perspectives for monitoring and controlling in-vivo cavitation.

  16. Desert dust suppressing precipitation: a possible desertification feedback loop.

    PubMed

    Rosenfeld, D; Rudich, Y; Lahav, R

    2001-05-22

    The effect of desert dust on cloud properties and precipitation has so far been studied solely by using theoretical models, which predict that rainfall would be enhanced. Here we present observations showing the contrary; the effect of dust on cloud properties is to inhibit precipitation. Using satellite and aircraft observations we show that clouds forming within desert dust contain small droplets and produce little precipitation by drop coalescence. Measurement of the size distribution and the chemical analysis of individual Saharan dust particles collected in such a dust storm suggest a possible mechanism for the diminished rainfall. The detrimental impact of dust on rainfall is smaller than that caused by smoke from biomass burning or anthropogenic air pollution, but the large abundance of desert dust in the atmosphere renders it important. The reduction of precipitation from clouds affected by desert dust can cause drier soil, which in turn raises more dust, thus providing a possible feedback loop to further decrease precipitation. Furthermore, anthropogenic changes of land use exposing the topsoil can initiate such a desertification feedback process.

  17. Desert dust suppressing precipitation: A possible desertification feedback loop

    PubMed Central

    Rosenfeld, Daniel; Rudich, Yinon; Lahav, Ronen

    2001-01-01

    The effect of desert dust on cloud properties and precipitation has so far been studied solely by using theoretical models, which predict that rainfall would be enhanced. Here we present observations showing the contrary; the effect of dust on cloud properties is to inhibit precipitation. Using satellite and aircraft observations we show that clouds forming within desert dust contain small droplets and produce little precipitation by drop coalescence. Measurement of the size distribution and the chemical analysis of individual Saharan dust particles collected in such a dust storm suggest a possible mechanism for the diminished rainfall. The detrimental impact of dust on rainfall is smaller than that caused by smoke from biomass burning or anthropogenic air pollution, but the large abundance of desert dust in the atmosphere renders it important. The reduction of precipitation from clouds affected by desert dust can cause drier soil, which in turn raises more dust, thus providing a possible feedback loop to further decrease precipitation. Furthermore, anthropogenic changes of land use exposing the topsoil can initiate such a desertification feedback process. PMID:11353821

  18. 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.

  19. 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)…

  20. Implementing Audio Digital Feedback Loop Using the National Instruments RIO System

    SciTech Connect

    Huang, G.; Byrd, J. M.

    2006-11-20

    Development of system for high precision RF distribution and laser synchronization at Berkeley Lab has been ongoing for several years. Successful operation of these systems requires multiple audio bandwidth feedback loops running at relatively high gains. Stable operation of the feedback loops requires careful design of the feedback transfer function. To allow for flexible and compact implementation, we have developed digital feedback loops on the National Instruments Reconfigurable Input/Output (RIO) platform. This platform uses an FPGA and multiple I/Os that can provide eight parallel channels running different filters. We present the design and preliminary experimental results of this system.

  1. 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

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

    PubMed

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

    2014-12-22

    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.

  3. 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

  4. Role of measurement voltage on hysteresis loop shape in Piezoresponse Force Microscopy

    SciTech Connect

    Kim, Yunseok; Yang, J.-C.; Chu, Ying Hao; Yu, Pu; Lu, X.; Jesse, Stephen; Kalinin, Sergei V

    2012-01-01

    The dependence of on-field and off-field hysteresis loop shape in Piezoresponse Force Microscopy (PFM) on driving voltage, Vac, is explored. A nontrivial dependence of hysteresis loop parameters on measurement conditions is observed. The strategies to distinguish between paraelectric and ferroelectric states with small coercive bias and separate reversible hysteretic and non-hysteretic behaviors are suggested. Generally, measurement of loop evolution with Vac is a necessary step to establish the veracity of PFM hysteresis measurements.

  5. 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.

  6. 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

  7. 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,…

  8. 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.

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

    DOE PAGES

    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

  10. 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.

  11. 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…

  12. 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.

  13. Identification of feedback loops embedded in cellular circuits by investigating non-causal impulse response components.

    PubMed

    Dong, Chao-Yi; Yoon, Tae-Woong; Bates, Declan G; Cho, Kwang-Hyun

    2010-02-01

    Feedback circuits are crucial dynamic motifs which occur in many biomolecular regulatory networks. They play a pivotal role in the regulation and control of many important cellular processes such as gene transcription, signal transduction, and metabolism. In this study, we develop a novel computationally efficient method to identify feedback loops embedded in intracellular networks, which uses only time-series experimental data and requires no knowledge of the network structure. In the proposed approach, a non-parametric system identification technique, as well as a spectral factor analysis, is applied to derive a graphical criterion based on non-causal components of the system's impulse response. The appearance of non-causal components in the impulse response sequences arising from stochastic output perturbations is shown to imply the presence of underlying feedback connections within a linear network. In order to extend the approach to nonlinear networks, we linearize the intracellular networks about an equilibrium point, and then choose the magnitude of the output perturbations sufficiently small so that the resulting time-series responses remain close to the chosen equilibrium point. In this way, the impulse response sequences of the linearized system can be used to determine the presence or absence of feedback loops in the corresponding nonlinear network. The proposed method utilizes the time profile data from intracellular perturbation experiments and only requires the perturbability of output nodes. Most importantly, the method does not require any a priori knowledge of the system structure. For these reasons, the proposed approach is very well suited to identifying feedback loops in large-scale biomolecular networks. The effectiveness of the proposed method is illustrated via two examples: a synthetic network model with a negative feedback loop and a nonlinear caspase function model of apoptosis with a positive feedback loop. PMID:19333603

  14. Dynamics of the interlocked positive feedback loops explaining the robust epigenetic switching in Candida albicans.

    PubMed

    Sriram, K; Soliman, Sylvain; Fages, François

    2009-05-01

    The two element mutual activation and inhibitory positive feedback loops are a common motifs that occur in many biological systems in both isolated and interlocked form, as for example, in the cell division cycle and thymus differentiation in eukaryotes. The properties of three element interlocked positive feedback loops that embeds both mutual activation and inhibition are studied in depth for their bistable properties by performing bifurcation and stochastic simulations. Codimension one and two bifurcations reveal important properties like robustness to parameter variations and adaptability under various conditions by its ability to fine tune the threshold to a wide range of values and to maintain a wide bistable regime. Furthermore, we show that in the interlocked circuit, mutual inhibition controls the decision to switch from OFF to ON state, while mutual activation enforces the decision. This view is supported through a concrete biological example Candida albicans, a human fungal pathogen that can exist in two distinctive cell types; one in the default white state and the other in an opaque form. Stochastic switching between these two forms takes place due to the epigenetic alternation induced by the transcriptional regulators in the circuit, albeit without any rearrangement of the nuclear chromosomes. The transcriptional regulators constitute interlocked mutual activation and inhibition feedback circuits that provide adaptable threshold and wide bistable regime. These positive feedback loops are shown to be responsible for robust noise induced transitions without chattering, persistence of particular phenotypes for many generations and selective exhibition of one particular form of phenotype when mutated. Finally, we propose for synthetic biology constructs to use interlocked positive feedback loops instead of two element positive feedback loops because they are better controlled than isolated mutual activation and mutual inhibition feedback circuits. PMID

  15. 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.

  16. 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.

  17. 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

  18. 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…

  19. 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

  20. Hybrid FES orthosis incorporating closed loop control and sensory feedback.

    PubMed

    Andrews, B J; Baxendale, R H; Barnett, R; Phillips, G F; Yamazaki, T; Paul, J P; Freeman, P A

    1988-04-01

    A hybrid functional electrical stimulation (FES) orthosis is described, comprising a rigid ankle-foot brace, a multi-channel FES stimulator with surface electrodes, body mounted sensors, a 'rule-based' controller and an electro-cutaneous display for supplementary sensory feedback. The mechanical brace provides stability, without FES activation of muscles, for standing postures normally adopted by patients. This avoids inducing muscle fatigue during prolonged upright activity. However, stability is conditional upon the position of the ground reaction vector (GRV) relative to the knee joint. The finite state FES controller reacts automatically to destabilizing shifts of the GRV by stimulating appropriate anti-gravity musculature to brace the leg. The FES system also features a control mode to initiate and terminate flexion of the leg during forward progression. A simple mode of supplementary sensory feedback was used during the laboratory standing tests to assist the patient in maintaining a set posture. Preliminary results of laboratory tests for two spinal cord injured subjects are presented. PMID:3361878

  1. The combination of positive and negative feedback loops confers exquisite flexibility to biochemical switches

    NASA Astrophysics Data System (ADS)

    Pfeuty, Benjamin; Kaneko, Kunihiko

    2009-12-01

    A wide range of cellular processes require molecular regulatory pathways to convert a graded signal into a discrete response. One prevalent switching mechanism relies on the coexistence of two stable states (bistability) caused by positive feedback regulations. Intriguingly, positive feedback is often supplemented with negative feedback, raising the question of whether and how these two types of feedback can cooperate to control discrete cellular responses. To address this issue, we formulate a canonical model of a protein-protein interaction network and analyze the dynamics of a prototypical two-component circuit. The appropriate combination of negative and positive feedback loops can bring a bistable circuit close to the oscillatory regime. Notably, sharply activated negative feedback can give rise to a bistable regime wherein two stable fixed points coexist and may collide pairwise with two saddle points. This specific type of bistability is found to allow for separate and flexible control of switch-on and switch-off events, for example (i) to combine fast and reversible transitions, (ii) to enable transient switching responses and (iii) to display tunable noise-induced transition rates. Finally, we discuss the relevance of such bistable switching behavior, and the circuit topologies considered, to specific biological processes such as adaptive metabolic responses, stochastic fate decisions and cell-cycle transitions. Taken together, our results suggest an efficient mechanism by which positive and negative feedback loops cooperate to drive the flexible and multifaceted switching behaviors arising in biological systems.

  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 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

  4. 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.

  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. Variable-ratio schedules as variable-interval schedules with linear feedback loops.

    PubMed

    McDowell, J J; Wixted, J T

    1986-11-01

    The mathematical theory of linear systems has been used successfully to describe responding on variable-interval (VI) schedules. In the simplest extension of the theory to the variable-ratio (VR) case, VR schedules are treated as if they were VI schedules with linear feedback loops. The assumption entailed by this approach, namely, that VR and VI-plus-linear-feedback schedules are equivalent, was tested by comparing responding on the two types of schedule. Four human subjects' lever pressing produced monetary reinforcers on five VR schedules, and on five VI schedules with linear feedback loops that reproduced the feedback properties of the VR schedules. Pressing was initiated by instructions in 2 subjects, and was shaped by successive approximation in the other 2. The different methods of response initiation did not have differential effects on behavior. For each of the 4 subjects, the VR and the comparable VI-plus-linear-feedback schedules generated similar average response rates and similar response patterns. The subjects' behavior on both types of schedule was similar to that of avian and rodent species on VR schedules. These results indicate that the assumption entailed by the VI-plus-linear-feedback approach to the VR case is valid and, consequently, that the approach is worth pursuing. The results also confute interresponse-time theories of schedule performance, which require interval and ratio contingencies to produce different response rates.

  8. 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.

  9. A digital feedback controller application for studying photoreceptor adaptation by 'voltage clamp by light'.

    PubMed

    Djupsund, K; Kouvalainen, E; Järvilehto, M; Weckström, M

    1995-11-01

    We present a new digital feedback application for the study of the sensitivity characteristics of photoreceptors. The amplitude of the recorded membrane voltage of a cell is steered by changing the incoming light intensity with a motor-driven circular, linear neutral-density wedge (CFW). The voltage response is sampled and fed to a software position controller of the CFW. The controller determines the position of the wedge according to the desired (command) value of the response. The light intensity changes during steady-state represent the sensitivity change, the time-course of adaptation.

  10. Feedback loops and reciprocal regulation: recurring motifs in the systems biology of the cell cycle

    PubMed Central

    Ferrell, James E.

    2013-01-01

    The study of eukaryotic cell cycle regulation over the last several decades has led to a remarkably detailed understanding of the complex regulatory system that drives this fundamental process. This allows us to now look for recurring motifs in the regulatory system. Among these are negative feedback loops, which underpin checkpoints and generate cell cycle oscillations; positive feedback loops, which promote oscillations and make cell cycle transitions switch-like and unidirectional; and reciprocal regulation, which can increase the control a key regulator exerts. These simple motifs are found at multiple points in the cell cycle (e.g., S-phase and M-phase control) and are conserved in diverse organisms. These findings argue for an underlying unity in the principles of cell cycle control. PMID:23927869

  11. Performance of a modified feedback loop adaptive array with TVRO satellite signals

    NASA Technical Reports Server (NTRS)

    Steadman, K.; Gupta, I. J.; Walton, E. K.

    1990-01-01

    The performance of an experimental adaptive antenna array system is evaluated using television-receive-only (TVRO) satellite signals. The experimental system is a sidelobe canceler with two auxiliary channels. Modified feedback loops are used to enhance the suppression of weak interfering signals. The modified feedback loops use two spatially separate antennas, each with an individual amplifier for each auxiliary channel. Thus, the experimental system uses five antenna elements. Instead of using five separate antennas, a reflector antenna with multiple feeds is used to receive signals from various TVRO satellites. The details of the earth station are given. It is shown that the experimental system can null up to two signals originating from interfering TVRO satellites while receiving the signals from a desired TVRO satellite.

  12. Q-factor enhancement for self-actuated self-sensing piezoelectric MEMS resonators applying a lock-in driven feedback loop

    NASA Astrophysics Data System (ADS)

    Kucera, M.; Manzaneque, T.; Sánchez-Rojas, J. L.; Bittner, A.; Schmid, U.

    2013-08-01

    This paper presents a robust Q-control approach based on an all-electrical feedback loop enhancing the quality factor of a resonant microstructure by using the self-sensing capability of a piezoelectric thin film actuator made of aluminium nitride. A lock-in amplifier is used to extract the feedback signal which is proportional to the piezoelectric current. The measured real part is used to replace the originally low-quality and noisy feedback signal to modulate the driving voltage of the piezoelectric thin-film actuator. Since the lock-in amplifier reduces the noise in the feedback signal substantially, the proposed enhancement loop avoids the disadvantage of a constant signal-to-noise ratio, which an analogue feedback circuit usually suffers from. The quality factor was increased from the intrinsic value of 1766 to a maximum of 34 840 in air. These promising results facilitate precise measurements for self-actuated and self-sensing MEMS cantilevers even when operated in static viscous media.

  13. 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.

  14. EFA6 controls Arf1 and Arf6 activation through a negative feedback loop.

    PubMed

    Padovani, Dominique; Folly-Klan, Marcia; Labarde, Audrey; Boulakirba, Sonia; Campanacci, Valérie; Franco, Michel; Zeghouf, Mahel; Cherfils, Jacqueline

    2014-08-26

    Guanine nucleotide exchange factors (GEFs) of the exchange factor for Arf6 (EFA6), brefeldin A-resistant Arf guanine nucleotide exchange factor (BRAG), and cytohesin subfamilies activate small GTPases of the Arf family in endocytic events. These ArfGEFs carry a pleckstrin homology (PH) domain in tandem with their catalytic Sec7 domain, which is autoinhibitory and supports a positive feedback loop in cytohesins but not in BRAGs, and has an as-yet unknown role in EFA6 regulation. In this study, we analyzed how EFA6A is regulated by its PH and C terminus (Ct) domains by reconstituting its GDP/GTP exchange activity on membranes. We found that EFA6 has a previously unappreciated high efficiency toward Arf1 on membranes and that, similar to BRAGs, its PH domain is not autoinhibitory and strongly potentiates nucleotide exchange on anionic liposomes. However, in striking contrast to both cytohesins and BRAGs, EFA6 is regulated by a negative feedback loop, which is mediated by an allosteric interaction of Arf6-GTP with the PH-Ct domain of EFA6 and monitors the activation of Arf1 and Arf6 differentially. These observations reveal that EFA6, BRAG, and cytohesins have unanticipated commonalities associated with divergent regulatory regimes. An important implication is that EFA6 and cytohesins may combine in a mixed negative-positive feedback loop. By allowing EFA6 to sustain a pool of dormant Arf6-GTP, such a circuit would fulfill the absolute requirement of cytohesins for activation by Arf-GTP before amplification of their GEF activity by their positive feedback loop.

  15. A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis

    PubMed Central

    Chen, Jun; Xu, Na; Huang, Huanwei; Cai, Tao; Xi, Rongwen

    2016-01-01

    Homeostatic renewal of many adult tissues requires balanced self-renewal and differentiation of local stem cells, but the underlying mechanisms are poorly understood. Here we identified a novel feedback mechanism in controlling intestinal regeneration and tumorigenesis in Drosophila. Sox21a, a group B Sox protein, is preferentially expressed in the committed progenitor named enteroblast (EB) to promote enterocyte differentiation. In Sox21a mutants, EBs do not divide, but cannot differentiate properly and have increased expression of mitogens, which then act as paracrine signals to promote intestinal stem cell (ISC) proliferation. This leads to a feedback amplification loop for rapid production of differentiation-defective EBs and tumorigenesis. Notably, in normal intestine following damage, Sox21a is temporally downregulated in EBs to allow the activation of the ISC-EB amplification loop for epithelial repair. We propose that executing a feedback amplification loop between stem cells and their progeny could be a common mechanism underlying tissue regeneration and tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.14330.001 PMID:27187149

  16. 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

  17. Wheels within wheels: new transcriptional feedback loops in the Arabidopsis circadian clock.

    PubMed

    McClung, C Robertson

    2014-01-01

    The circadian clock allows organisms to temporally coordinate their biology with the diurnal oscillation of the environment, which enhances plant performance. Accordingly, a fuller understanding of the circadian clock mechanism may contribute to efforts to optimize plant performance. One recurring theme in clock mechanism is coupled transcription-translation feedback loops. To date, the majority of plant transcription factors constituting these loops, including the central oscillator components CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), LATE ELONGATED HYPOCOTYL (LHY), and TIMING OF CAB2 EXPRESSION 1 (TOC1), and the related PSEUDO-RESPONSE REGULATORS (PRRs), are transcriptional repressors, leading to a model of the clock emphasizing repressive interactions. Recent work, however, has revealed that a subset of the REVEILLE (RVE) family of Myb transcription factors closely related to CCA1 and LHY are transcriptional activators in novel feedback transcription-translation feedback loops. Other recently identified transcriptional activators that contribute to clock function include LIGHT-REGULATED WD 1 (LWD1) and LWD2 and night light-inducible and clock-regulated transcription factors NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED1 (LNK1) and LNK2. Collectively, these advances permit a substantial reconfiguration of the clock model.

  18. Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses

    PubMed Central

    Kriete, Andres; Bosl, William J.; Booker, Glenn

    2010-01-01

    Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive-feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-κB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype. PMID:20585546

  19. 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.

  20. 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.

  1. Anatomy of a negative feedback loop: the case of IκBα.

    PubMed

    Fagerlund, Riku; Behar, Marcelo; Fortmann, Karen T; Lin, Y Eason; Vargas, Jesse D; Hoffmann, Alexander

    2015-09-01

    The magnitude, duration and oscillation of cellular signalling pathway responses are often limited by negative feedback loops, defined as an 'activator-induced inhibitor' regulatory motif. Within the NFκB signalling pathway, a key negative feedback regulator is IκBα. We show here that, contrary to current understanding, NFκB-inducible expression is not sufficient for providing effective negative feedback. We then employ computational simulations of NFκB signalling to identify IκBα molecular properties that are critical for proper negative feedback control and test the resulting predictions in biochemical and single-cell live-imaging studies. We identified nuclear import and nuclear export of IκBα and the IκBα-NFκB complex, as well as the free IκBα half-life, as key determinants of post-induction repression of NFκB and the potential for subsequent reactivation. Our work emphasizes that negative feedback is an emergent systems property determined by multiple molecular and biophysical properties in addition to the required 'activator-induced inhibitor' relationship. PMID:26311312

  2. 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

  3. 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

  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 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.

  5. 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.

  6. 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.

  7. Fine-tuning of voltage sensitivity of the Kv1.2 potassium channel by interhelix loop dynamics.

    PubMed

    Sand, Rheanna; Sharmin, Nazlee; Morgan, Carla; Gallin, Warren J

    2013-04-01

    Many proteins function by changing conformation in response to ligand binding or changes in other factors in their environment. Any change in the sequence of a protein, for example during evolution, which alters the relative free energies of the different functional conformations changes the conditions under which the protein will function. Voltage-gated ion channels are membrane proteins that open and close an ion-selective pore in response to changes in transmembrane voltage. The charged S4 transmembrane helix transduces changes in transmembrane voltage into a change in protein internal energy by interacting with the rest of the channel protein through a combination of non-covalent interactions between adjacent helices and covalent interactions along the peptide backbone. However, the structural basis for the wide variation in the V50 value between different voltage-gated potassium channels is not well defined. To test the role of the loop linking the S3 helix and the S4 helix in voltage sensitivity, we have constructed a set of mutants of the rat Kv1.2 channel that vary solely in the length and composition of the extracellular loop that connects S4 to S3. We evaluated the effect of these different loop substitutions on the voltage sensitivity of the channel and compared these experimental results with molecular dynamics simulations of the loop structures. Here, we show that this loop has a significant role in setting the precise V50 of activation in Kv1 family channels.

  8. Sensory and decision-related activity propagate in a cortical feedback loop during touch perception.

    PubMed

    Kwon, Sung Eun; Yang, Hongdian; Minamisawa, Genki; O'Connor, Daniel H

    2016-09-01

    The brain transforms physical sensory stimuli into meaningful perceptions. In animals making choices about sensory stimuli, neuronal activity in successive cortical stages reflects a progression from sensation to decision. Feedforward and feedback pathways connecting cortical areas are critical for this transformation. However, the computational functions of these pathways are poorly understood because pathway-specific activity has rarely been monitored during a perceptual task. Using cellular-resolution, pathway-specific imaging, we measured neuronal activity across primary (S1) and secondary (S2) somatosensory cortices of mice performing a tactile detection task. S1 encoded the stimulus better than S2, while S2 activity more strongly reflected perceptual choice. S1 neurons projecting to S2 fed forward activity that predicted choice. Activity encoding touch and choice propagated in an S1-S2 loop along feedforward and feedback axons. Our results suggest that sensory inputs converge into a perceptual outcome as feedforward computations are reinforced in a feedback loop. PMID:27437910

  9. Protein kinase A and casein kinases mediate sequential phosphorylation events in the circadian negative feedback loop.

    PubMed

    Huang, Guocun; Chen, She; Li, Shaojie; Cha, Joonseok; Long, Chengzu; Li, Lily; He, Qiyang; Liu, Yi

    2007-12-15

    Regulation of circadian clock components by phosphorylation plays essential roles in clock functions and is conserved from fungi to mammals. In the Neurospora circadian negative feedback loop, FREQUENCY (FRQ) protein inhibits WHITE COLLAR (WC) complex activity by recruiting the casein kinases CKI and CKII to phosphorylate the WC proteins, resulting in the repression of frq transcription. On the other hand, CKI and CKII progressively phosphorylate FRQ to promote FRQ degradation, a process that is a major determinant of circadian period length. Here, by using whole-cell isotope labeling and quantitative mass spectrometry methods, we show that the WC-1 phosphorylation events critical for the negative feedback process occur sequentially-first by a priming kinase, then by the FRQ-recruited casein kinases. We further show that the cyclic AMP-dependent protein kinase A (PKA) is essential for clock function and inhibits WC activity by serving as a priming kinase for the casein kinases. In addition, PKA also regulates FRQ phosphorylation, but unlike CKI and CKII, PKA stabilizes FRQ, similar to the stabilization of human PERIOD2 (hPER2) due to the phosphorylation at the familial advanced sleep phase syndrome (FASPS) site. Thus, PKA is a key clock component that regulates several critical processes in the circadian negative feedback loop. PMID:18079175

  10. The role of optoelectronic feedback on Franz-Keldysh voltage modulation of transistor lasers

    NASA Astrophysics Data System (ADS)

    Chang, Chi-Hsiang; Chang, Shu-Wei; Wu, Chao-Hsin

    2016-03-01

    Possessing both the high-speed characteristics of heterojunction bipolar transistors (HBTs) and enhanced radiative recombination of quantum wells (QWs), the light-emitting transistor (LET) which operates in the regime of spontaneous emissions has achieved up to 4.3 GHz modulation bandwidth. A 40 Gbit/s transmission rate can be even achieved using transistor laser (TL). The transistor laser provides not only the current modulation but also direct voltage-controlled modulation scheme of optical signals via Franz-Keldysh (FK) photon-assisted tunneling effect. In this work, the effect of FK absorption on the voltage modulation of TLs is investigated. In order to analyze the dynamics and optical responses of voltage modulation in TLs, the conventional rate equations relevant to diode lasers (DLs) are first modified to include the FK effect intuitively. The theoretical results of direct-current (DC) and small-signal alternating-current (AC) characteristics of optical responses are both investigated. While the DC characteristics look physical, the intrinsic optical response of TLs under the FK voltage modulation shows an AC enhancement with a 20 dB peak, which however is not observed in experiment. A complete model composed of the intrinsic optical transfer function and an electrical transfer function fed back by optical responses is proposed to explain the behaviors of voltage modulation in TLs. The abnormal AC peak disappears through this optoelectronic feedback. With the electrical response along with FK-included photon-carrier rate equations taken into account, the complete voltage-controlled optical modulation response of TLs is demonstrated.

  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. 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.

  13. Dissection of a Krox20 positive feedback loop driving cell fate choices in hindbrain patterning

    PubMed Central

    Bouchoucha, Yassine X; Reingruber, Jürgen; Labalette, Charlotte; Wassef, Michel A; Thierion, Elodie; Desmarquet-Trin Dinh, Carole; Holcman, David; Gilardi-Hebenstreit, Pascale; Charnay, Patrick

    2013-01-01

    Although feedback loops are essential in development, their molecular implementation and precise functions remain elusive. Using enhancer knockout in mice, we demonstrate that a direct, positive autoregulatory loop amplifies and maintains the expression of Krox20, a transcription factor governing vertebrate hindbrain segmentation. By combining quantitative data collected in the zebrafish with biophysical modelling that accounts for the intrinsic stochastic molecular dynamics, we dissect the loop at the molecular level. We find that it underpins a bistable switch that turns a transient input signal into cell fate commitment, as we observe in single cell analyses. The stochasticity of the activation process leads to a graded input–output response until saturation is reached. Consequently, the duration and strength of the input signal controls the size of the hindbrain segments by modulating the distribution between the two cell fates. Moreover, segment formation is buffered from severe variations in input level. Finally, the progressive extinction of Krox20 expression involves a destabilization of the loop by repressor molecules. These mechanisms are of general significance for cell type specification and tissue patterning. PMID:24061538

  14. Quantitative assessment of the p53-Mdm2 feedback loop using protein lysate microarrays.

    PubMed

    Ramalingam, Sundhar; Honkanen, Peter; Young, Lynn; Shimura, Tsutomu; Austin, John; Steeg, Patricia S; Nishizuka, Satoshi

    2007-07-01

    Mathematical simulations of the p53-Mdm2 feedback loop suggest that both proteins will exhibit impulsive expression characteristics in response to high cellular stress levels. However, little quantitative experimental evaluation has been done, particularly of the phosphorylated forms. To evaluate the mathematical models experimentally, we used lysate microarrays from an isogenic pair of gamma-ray-irradiated cell lysates from HCT116 (p53(+/+) and p53(-/-)). Both p53 and Mdm2 proteins showed expected pulses in the wild type, whereas no pulses were seen in the knockout. Based on experimental observations, we determined model parameters and generated an in silico "knockout," reflecting the experimental data, including phosphorylated proteins.

  15. Regulation of epidermal cell fate in Arabidopsis roots: the importance of multiple feedback loops

    PubMed Central

    Schiefelbein, John; Huang, Ling; Zheng, Xiaohua

    2014-01-01

    The specification of distinct cell types in multicellular organisms is accomplished via establishment of differential gene expression. A major question is the nature of the mechanisms that establish this differential expression in time and space. In plants, the formation of the hair and non-hair cell types in the root epidermis has been used as a model to understand regulation of cell specification. Recent findings show surprising complexity in the number and the types of regulatory interactions between the multiple transcription factor genes/proteins influencing root epidermis cell fate. Here, we describe this regulatory network and the importance of the multiple feedback loops for its establishment and maintenance. PMID:24596575

  16. Analytically exploiting noise correlations inside the feedback loop to improve locked-oscillator performance.

    PubMed

    Sastrawan, J; Jones, C; Akhalwaya, I; Uys, H; Biercuk, M J

    2016-08-01

    We introduce concepts from optimal estimation to the stabilization of precision frequency standards limited by noisy local oscillators. We develop a theoretical framework casting various measures for frequency standard variance in terms of frequency-domain transfer functions, capturing the effects of feedback stabilization via a time series of Ramsey measurements. Using this framework, we introduce an optimized hybrid predictive feedforward measurement protocol that employs results from multiple past measurements and transfer-function-based calculations of measurement covariance to improve the accuracy of corrections within the feedback loop. In the presence of common non-Markovian noise processes these measurements will be correlated in a calculable manner, providing a means to capture the stochastic evolution of the local oscillator frequency during the measurement cycle. We present analytic calculations and numerical simulations of oscillator performance under competing feedback schemes and demonstrate benefits in both correction accuracy and long-term oscillator stability using hybrid feedforward. Simulations verify that in the presence of uncompensated dead time and noise with significant spectral weight near the inverse cycle time predictive feedforward outperforms traditional feedback, providing a path towards developing a class of stabilization software routines for frequency standards limited by noisy local oscillators. PMID:27627295

  17. Analytically exploiting noise correlations inside the feedback loop to improve locked-oscillator performance.

    PubMed

    Sastrawan, J; Jones, C; Akhalwaya, I; Uys, H; Biercuk, M J

    2016-08-01

    We introduce concepts from optimal estimation to the stabilization of precision frequency standards limited by noisy local oscillators. We develop a theoretical framework casting various measures for frequency standard variance in terms of frequency-domain transfer functions, capturing the effects of feedback stabilization via a time series of Ramsey measurements. Using this framework, we introduce an optimized hybrid predictive feedforward measurement protocol that employs results from multiple past measurements and transfer-function-based calculations of measurement covariance to improve the accuracy of corrections within the feedback loop. In the presence of common non-Markovian noise processes these measurements will be correlated in a calculable manner, providing a means to capture the stochastic evolution of the local oscillator frequency during the measurement cycle. We present analytic calculations and numerical simulations of oscillator performance under competing feedback schemes and demonstrate benefits in both correction accuracy and long-term oscillator stability using hybrid feedforward. Simulations verify that in the presence of uncompensated dead time and noise with significant spectral weight near the inverse cycle time predictive feedforward outperforms traditional feedback, providing a path towards developing a class of stabilization software routines for frequency standards limited by noisy local oscillators.

  18. Analytically exploiting noise correlations inside the feedback loop to improve locked-oscillator performance

    NASA Astrophysics Data System (ADS)

    Sastrawan, J.; Jones, C.; Akhalwaya, I.; Uys, H.; Biercuk, M. J.

    2016-08-01

    We introduce concepts from optimal estimation to the stabilization of precision frequency standards limited by noisy local oscillators. We develop a theoretical framework casting various measures for frequency standard variance in terms of frequency-domain transfer functions, capturing the effects of feedback stabilization via a time series of Ramsey measurements. Using this framework, we introduce an optimized hybrid predictive feedforward measurement protocol that employs results from multiple past measurements and transfer-function-based calculations of measurement covariance to improve the accuracy of corrections within the feedback loop. In the presence of common non-Markovian noise processes these measurements will be correlated in a calculable manner, providing a means to capture the stochastic evolution of the local oscillator frequency during the measurement cycle. We present analytic calculations and numerical simulations of oscillator performance under competing feedback schemes and demonstrate benefits in both correction accuracy and long-term oscillator stability using hybrid feedforward. Simulations verify that in the presence of uncompensated dead time and noise with significant spectral weight near the inverse cycle time predictive feedforward outperforms traditional feedback, providing a path towards developing a class of stabilization software routines for frequency standards limited by noisy local oscillators.

  19. A Self-regulatory System of Interlinked Signaling Feedback Loops Controls Mouse Limb Patterning

    NASA Astrophysics Data System (ADS)

    Benazet, Jean-Denis; Bischofberger, Mirko; Tiecke, Eva; Gonalves, Alexandre; Martin, James F.; Zuniga, Aime; Naef, Felix; Zeller, Rolf

    Developmental pathways need to be robust against environmental and genetic variation to enable reliable morphogenesis. Here, we take a systems biology approach to explain how robustness is achieved in the developing mouse limb, a classical model of organogenesis. By combining quantitative genetics with computational modeling we established a computational model of multiple interlocked feedback modules, involving sonic hedgehog (SHH) morphogen, fibroblast growth factor (FGFs) signaling, bone morphogenetic protein (BMP) and its antagonist GREM1. Earlier modeling work had emphasized the versatile kinetic characteristics of interlocked feedback loops operating at different time scales. Here we develop and then validate a similar computational model to show how BMP4 first initiates and SHH then propagates feedback in the network through differential transcriptional regulation of Grem1 to control digit specification. This switch occurs by linking a fast BMP4/GREM1 module to a slower SHH/GREM1/FGF feedback loop. Simulated gene expression profiles modeled normal limb development as well those of single-gene knockouts. Sensitivity analysis showed how the model was robust and insensitive to variability in parameters. A surprising prediction of the model was that an early Bmp4 signal is essential to kick-start Grem1 expression and the digit specification system. We experimentally validated the prediction using inducible alleles and showed that early, but not late, removal of Bmp4 dramatically disrupted limb development. Sensitivity analysis showed how robustness emerges from this circuitry. This study shows how modeling and computation can help us understand how self-regulatory signaling networks achieve robust regulation of limb development, by exploiting interconnectivity among the three signaling pathways. We expect that similar computational analyses will shed light on the origins of robustness in other developmental systems, and I will discuss some recent examples from

  20. 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

  1. Experimental Verification of Application of Looped System and Centralized Voltage Control in a Distribution System with Renewable Energy Sources

    NASA Astrophysics Data System (ADS)

    Hanai, Yuji; Hayashi, Yasuhiro; Matsuki, Junya

    The line voltage control in a distribution network is one of the most important issues for a penetration of Renewable Energy Sources (RES). A loop distribution network configuration is an effective solution to resolve voltage and distribution loss issues concerned about a penetration of RES. In this paper, for a loop distribution network, the authors propose a voltage control method based on tap change control of LRT and active/reactive power control of RES. The tap change control of LRT takes a major role of the proposed voltage control. Additionally the active/reactive power control of RES supports the voltage control when voltage deviation from the upper or lower voltage limit is unavoidable. The proposed method adopts SCADA system based on measured data from IT switches, which are sectionalizing switch with sensor installed in distribution feeder. In order to check the validity of the proposed voltage control method, experimental simulations using a distribution system analog simulator “ANSWER” are carried out. In the simulations, the voltage maintenance capability in the normal and the emergency is evaluated.

  2. 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.

  3. 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.

  4. A Positive Feedback Loop Involving Haspin and Aurora B Promotes CPC Accumulation at Centromeres in Mitosis

    PubMed Central

    Wang, Fangwei; Ulyanova, Natalia P.; van der Waal, Maike S.; Patnaik, Debasis; Lens, Susanne M.A.; Higgins, Jonathan M.G.

    2011-01-01

    Summary Haspin phosphorylates histone H3 at Thr-3 (H3T3ph) during mitosis [1, 2], providing a chromatin binding site for the chromosomal passenger complex (CPC) at centromeres to regulate chromosome segregation [3–5]. H3T3ph becomes increasingly focused at inner centromeres during prometaphase [1, 2], but little is known about how its level or location and the consequent chromosomal localization of the CPC are regulated. In addition, CPC binding to Shugoshin proteins contributes to centromeric Aurora B localization [5, 6]. Recruitment of the Shugoshins to centromeres requires the phosphorylation of Histone H2A at T120 (H2AT120ph) by the kinetochore kinase Bub1 [7], but the molecular basis for the collaboration of this pathway with H3T3ph has been unclear. Here, we show that Aurora B phosphorylates Haspin to promote generation of H3T3ph, and that Aurora B kinase activity is required for normal chromosomal localization of the CPC, indicating an intimate linkage between Aurora B and Haspin functions in mitosis. We propose that Aurora B activity triggers a CPC-Haspin-H3T3ph feedback loop that promotes generation of H3T3ph on chromatin. We also provide evidence that the Bub1-Shugoshin-CPC pathway supplies a signal that boosts the CPC-Haspin-H3T3ph feedback loop specifically at centromeres to produce the well-known accumulation of the CPC in these regions. PMID:21658950

  5. 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.

  6. Robust stability analysis and design under consideration of multiple feedback loops of the tryptophan regulatory network of Escherichia coli.

    PubMed

    Meyer-Baese, A; Theis, F; Emmett, M R

    2010-01-01

    The tryptophan system present in Escherichia coli represents an important regulatory unit described by multiple feedback loops. The role of these feedback loops is crucial for the analysis of the dynamical behavior of the tryptophan synthesis. We analyze the robust stability of this system which models the dynamics of both fast state, such as transcription and synthesis of free operator, and slow state, such as translation and tryptophan synthesis under consideration of nonlinear uncertainties. In addition, we analyze the role of these feedback loops as key design components of this regulatory unit responsible for its physiological performance. The range of allowed parameter perturbations and the conditions that ensure the existence of asymptotically stable equilibria of the perturbed system are determined. We also analyze two important alternate regulatory designs for the tryptophan synthesis pathway and derive the stability conditions. PMID:20865501

  7. Voltage tunable multiple quantum well distributed feedback filter with an electron beam written Schottky grating

    NASA Astrophysics Data System (ADS)

    Zia, O.; Bhattacharya, P. K.; Singh, J.; Brock, T.

    1994-08-01

    A novel optoelectronic filter voltage-tunable characteristics has been developed and implemented in a multiquantum well waveguide device. By virtue of the quantum-confined Stark effect, the refractive index in quantum wells at the periphery of a guiding region can be given a periodicity in the guiding direction by application of a bias on an electron-beam patterned Schottky grating atop the guide. If the period of the Schottky grating and associated index profile satisfies the Bragg condition, as in a resonant distributed feedback structure, band-reject filtering results. Aftering the bias on the Schottky grating changes the refractive index in the wells, thereby providing tunability of the wavelength at which Bragg diffraction occurs.

  8. An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma

    PubMed Central

    Drier, Yotam; Cotton, Matthew J.; Williamson, Kaylyn E.; Gillespie, Shawn M.; Ryan, Russell J.H.; Kluk, Michael J.; Carey, Christopher D.; Rodig, Scott J.; Sholl, Lynette M; Afrogheh, Amir H.; Faquin, William C.; Queimado, Lurdes; Qi, Jun; Wick, Michael J.; El-Naggar, Adel K.; Bradner, James E.; Moskaluk, Christopher A.; Aster, Jon C.; Knoechel, Birgit; Bernstein, Bradley E.

    2016-01-01

    Translocation events are frequent in cancer and may create chimeric fusions or ‘regulatory rearrangements’ that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole-genome sequencing data and chromatin maps reveal distinct chromosomal rearrangements that juxtapose super-enhancers to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers interact with the MYB promoter. Remarkably, MYB protein binds to the translocated enhancers, creating a positive feedback loop that sustains its expression. MYB also binds enhancers that drive different regulatory programs in alternate cell lineages in ACC, cooperating with TP63 in myoepithelial cells and a Notch program in luminal epithelial cells. Bromodomain inhibitors slow tumor growth in ACC primagraft models in vivo. Thus, our study identifies super-enhancer translocations that drive MYB expression and provides insight into downstream MYB functions in the alternate ACC lineages. PMID:26829750

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. Investigating dynamics of inhibitory and feedback loops in ERK signalling using power-law models.

    PubMed

    Vera, Julio; Rath, Oliver; Balsa-Canto, Eva; Banga, Julio R; Kolch, Walter; Wolkenhauer, Olaf

    2010-11-01

    the existence of an intense feedback-loop control of the pathway by the activated ERK that maybe responsible for the damped oscillations we saw in the fraction of activated MEK both in the experiments and simulations. In addition, the model analysis suggested that phosphorylation/deactivation of RKIP during the transient stimulation may have a significant effect on the signalling peaks of both MEK and ERK. This later result suggests that dynamic modulation of signal inhibitors during stimulation may be a regulatory mechanism in ERK signalling and other pathways.

  14. 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.

  15. 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

  16. An excitatory cortical feedback loop gates retinal wave transmission in rodent thalamus

    PubMed Central

    Murata, Yasunobu; Colonnese, Matthew T

    2016-01-01

    Spontaneous retinal waves are critical for the development of receptive fields in visual thalamus (LGN) and cortex (VC). Despite a detailed understanding of the circuit specializations in retina that generate waves, whether central circuit specializations also exist to control their propagation through visual pathways of the brain is unknown. Here we identify a developmentally transient, corticothalamic amplification of retinal drive to thalamus as a mechanism for retinal wave transmission in the infant rat brain. During the period of retinal waves, corticothalamic connections excite LGN, rather than driving feedforward inhibition as observed in the adult. This creates an excitatory feedback loop that gates retinal wave transmission through the LGN. This cortical multiplication of retinal wave input ends just prior to eye-opening, as cortex begins to inhibit LGN. Our results show that the early retino-thalamo-cortical circuit uses developmentally specialized feedback amplification to ensure powerful, high-fidelity transmission of retinal activity despite immature connectivity. DOI: http://dx.doi.org/10.7554/eLife.18816.001 PMID:27725086

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

    PubMed

    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

    2015-09-01

    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.

  18. 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

  19. Sand and sandbar willow: a feedback loop amplifies environmental sensitivity at the riparian interface.

    PubMed

    Rood, Stewart B; Goater, Lori A; Gill, Karen M; Braatne, Jeffrey H

    2011-01-01

    Riparian or streamside zones support dynamic ecosystems with three interacting components: flowing water, alluvia (river-transported sediments), and vegetation. River damming influences all three, and subsequent responses can provide insight into underlying processes. We investigated these components along the 315-km Hells Canyon corridor of the Snake River that included reaches upstream, along, and downstream from three large dams and reservoirs, and along the Salmon River, a free-flowing tributary. Sandbar willow was generally the woody plant at the lowest bank position and was abundant along upstream reaches (53, 45, 67% of transects), sparse along reservoirs (11, 12, 0%), and sparse along the Snake River downstream (11%). It was prolific along the undammed Salmon River (83%) and intermediate along the Snake River below the Salmon inflow (27%), indicating partial recovery with the contribution of water and sediments. Along these rivers, it commonly occurred on sandy substrates, especially on shallow-sloped surfaces, and emerged from interstitial sands between cobbles on steeper surfaces. However, along the Snake River below the dams, sandbars have eroded and willows were sparse on remnant, degrading sand surfaces. We conclude that a feedback loop exists between sands and sandbar willow. Sand favors willow colonization and clonal expansion, and reciprocally the extensively branched willows create slack-water zones that protect and trap sands. This feedback may sustain surface sands and sandbar willows along free-flowing river systems and it amplifies their mutual vulnerability to river damming. Following damming, sediment-depleted water is released downstream, eroding surface sands and reducing willow colonization and expansion. With willow decline, sands are further exposed and eroded, compounding these impacts. From this feedback, we predict the coordinated depletion of surface sands and riparian willows along dammed rivers throughout the Northern Hemisphere.

  20. Sand and sandbar willow: a feedback loop amplifies environmental sensitivity at the riparian interface.

    PubMed

    Rood, Stewart B; Goater, Lori A; Gill, Karen M; Braatne, Jeffrey H

    2011-01-01

    Riparian or streamside zones support dynamic ecosystems with three interacting components: flowing water, alluvia (river-transported sediments), and vegetation. River damming influences all three, and subsequent responses can provide insight into underlying processes. We investigated these components along the 315-km Hells Canyon corridor of the Snake River that included reaches upstream, along, and downstream from three large dams and reservoirs, and along the Salmon River, a free-flowing tributary. Sandbar willow was generally the woody plant at the lowest bank position and was abundant along upstream reaches (53, 45, 67% of transects), sparse along reservoirs (11, 12, 0%), and sparse along the Snake River downstream (11%). It was prolific along the undammed Salmon River (83%) and intermediate along the Snake River below the Salmon inflow (27%), indicating partial recovery with the contribution of water and sediments. Along these rivers, it commonly occurred on sandy substrates, especially on shallow-sloped surfaces, and emerged from interstitial sands between cobbles on steeper surfaces. However, along the Snake River below the dams, sandbars have eroded and willows were sparse on remnant, degrading sand surfaces. We conclude that a feedback loop exists between sands and sandbar willow. Sand favors willow colonization and clonal expansion, and reciprocally the extensively branched willows create slack-water zones that protect and trap sands. This feedback may sustain surface sands and sandbar willows along free-flowing river systems and it amplifies their mutual vulnerability to river damming. Following damming, sediment-depleted water is released downstream, eroding surface sands and reducing willow colonization and expansion. With willow decline, sands are further exposed and eroded, compounding these impacts. From this feedback, we predict the coordinated depletion of surface sands and riparian willows along dammed rivers throughout the Northern Hemisphere

  1. Thermospermine levels are controlled by an auxin-dependent feedback loop mechanism in Populus xylem.

    PubMed

    Milhinhos, Ana; Prestele, Jakob; Bollhöner, Benjamin; Matos, Andreia; Vera-Sirera, Francisco; Rambla, José L; Ljung, Karin; Carbonell, Juan; Blázquez, Miguel A; Tuominen, Hannele; Miguel, Célia M

    2013-08-01

    Polyamines are small polycationic amines that are widespread in living organisms. Thermospermine, synthesized by thermospermine synthase ACAULIS5 (ACL5), was recently shown to be an endogenous plant polyamine. Thermospermine is critical for proper vascular development and xylem cell specification, but it is not known how thermospermine homeostasis is controlled in the xylem. We present data in the Populus model system supporting the existence of a negative feedback control of thermospermine levels in stem xylem tissues, the main site of thermospermine biosynthesis. While over-expression of the ACL5 homologue in Populus, POPACAULIS5, resulted in strong up-regulation of ACL5 expression and thermospermine accumulation in leaves, the corresponding levels in the secondary xylem tissues of the stem were similar or lower than those in the wild-type. POPACAULIS5 over-expression had a negative effect on accumulation of indole-3-acetic acid, while exogenous auxin had a positive effect on POPACAULIS5 expression, thus promoting thermospermine accumulation. Further, over-expression of POPACAULIS5 negatively affected expression of the class III homeodomain leucine zipper (HD-Zip III) transcription factor gene PttHB8, a homologue of AtHB8, while up-regulation of PttHB8 positively affected POPACAULIS5 expression. These results indicate that excessive accumulation of thermospermine is prevented by a negative feedback control of POPACAULIS5 transcript levels through suppression of indole-3-acetic acid levels, and that PttHB8 is involved in the control of POPACAULIS5 expression. We propose that this negative feedback loop functions to maintain steady-state levels of thermospermine, which is required for proper xylem development, and that it is dependent on the presence of high concentrations of endogenous indole-3-acetic acid, such as those present in the secondary xylem tissues.

  2. 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)

  3. 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.

  4. Surface potential imaging with atomic resolution by frequency-modulation Kelvin probe force microscopy without bias voltage feedback.

    PubMed

    Kou, Lili; Ma, Zongmin; Li, Yan Jun; Naitoh, Yoshitaka; Komiyama, Masaharu; Sugawara, Yasuhiro

    2015-05-15

    We investigated the capability of obtaining atomic resolution surface potential images by frequency-modulation Kelvin probe force microscopy (FM-KPFM) without bias voltage feedback. We theoretically derived equations representing the relationship between the contact potential difference and the frequency shift (Δf) of an oscillating cantilever. For the first time, we obtained atomic resolution images and site-dependent spectroscopic curves for Δf and VLCPD on a Si (111)-7 × 7 surface. FM-KPFM without bias voltage feedback does not involve the influence of the FM-KPFM controller because it has no deviation from a parabolic dependence of Δf on the dc-bias voltage. It is particularly suitable for investigation on molecular electronics and organic photovoltaics, because electron or ion movement induced by dc bias is avoided and the electrochemical reactions are inhibited. PMID:25895740

  5. 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.

  6. Neural approximation of open-loop feedback rate control in satellite networks.

    PubMed

    Baglietto, Marco; Davoli, Franco; Marchese, Mario; Mongelli, Maurizio

    2005-09-01

    A resource allocation problem for a satellite network is considered, where variations of fading conditions are added to those of traffic load. Since the capacity of the system is finite and divided in finite discrete portions, the resource allocation problem reveals to be a discrete stochastic programming one, which is typically NP-Hard. In practice, a good approximation of the optimal solution could be obtained through the adoption of a closed-form expression of the performance measure in steady-state conditions. Once we have summarized the drawbacks of such optimization strategy, we address two novel optimization approaches. The first one derives from Gokbayrak and Cassandras and is based on the minimization over the discrete constraint set using an estimate of the gradient, obtained through a "relaxed continuous extension" of the performance measure. The computation of the gradient estimation is based on infinitesimal perturbation analysis (IPA). Neither closed forms of the performance measures, nor additional feedbacks concerning the state of the system and very mild assumptions about the stochastic environment are requested. The second one is the main contribution of the present work, and is based on an open-loop feedback control (OLFC) strategy, aimed at providing optimal reallocation strategies as functions of the state of the network. The optimization approach leads us to a functional optimization problem, and we investigate the adoption of a neural network-based technique, in order to approximate its solution. As is shown in the simulation results, we obtain near-optimal reallocation strategies with a small real time computational effort and avoid the suboptimal transient periods introduced by the IPA gradient descent algorithm. PMID:16252826

  7. Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop.

    PubMed

    Valenti, Fabio; Fausti, Francesca; Biagioni, Francesca; Shay, Tal; Fontemaggi, Giulia; Domany, Eytan; Yaffe, Michael B; Strano, Sabrina; Blandino, Giovanni; Di Agostino, Silvia

    2011-12-15

    Aberrant activation of kinases has emerged to be a key event along with tumor progression, maintenance of tumor phenotype and response to anticancer treatments. This study documents the existence of an oncogenic auto-regulatory feedback loop that includes the Polo-like kinase-2 (Snk/Plk2) and mutant p53 proteins. Plk2 protein binds to and phosphorylates mutant p53, thereby potentiating its oncogenic activities. Phosphorylated mutant p53 binds more efficiently to p300 consequently strengthening its own transcriptional activity. Plk2 gene is regulated at a transcriptional level by both wt- and mutant p53 proteins. This leads to growth suppression or enhanced cell proliferation and chemo-resistance, respectively. In turn, the siRNA-mediated knock down of either mutant p53 or Plk2 proteins significantly curtails the growth properties of tumor cells and their chemo-resistance to anticancer treatments. Therefore, this paper identifies a novel tumor network including Plk2 and mutant p53 proteins whose triggering in response to DNA damage might disclose important implications for the treatment of human cancers. PMID:22134238

  8. 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.

  9. Transcriptional control of circadian hormone synthesis via the CREM feedback loop.

    PubMed

    Foulkes, N S; Borjigin, J; Snyder, S H; Sassone-Corsi, P

    1996-11-26

    Transcription factor cAMP-responsive element modulator (CREM) plays a key physiological and developmental role within the hypothalamic-pituitary-gonadal axis. The use of an alternative, intronic promoter within the CREM gene is responsible for the production of a cAMP-inducible repressor, inducible cAMP early repressor (ICER). ICER negatively autoregulates the ICER promoter, thus generating a feedback loop. We have previously documented a striking, clock-driven circadian fluctuation of CREM expression in the pineal gland. Oscillating ICER levels tightly correlate with fluctuations in the synthesis of the pineal hormone melatonin, whose production is also driven by the endogenous clock. Melatonin in turn regulates the hypothalamic-pituitary axis. The enzyme serotonin N-acetyltransferase (NAT) catalyzes the rate limiting step in melatonin synthesis. Thus, oscillations in NAT levels determine the circadian synthesis of melatonin. Here we demonstrate that NAT expression is dramatically increased in CREM-deficient mice that we have generated by homologous recombination. Characterization of the NAT promoter shows the presence of a ICER binding site. In addition, transfection studies show that ICER powerfully represses NAT transcription. Our results implicate CREM as a central regulator of output functions of the clock. Indeed, CREM acts as a key regulator of oscillatory hormonal synthesis.

  10. 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.

  11. Retinoic acid regulation of the Mesp-Ripply feedback loop during vertebrate segmental patterning.

    PubMed

    Moreno, Tanya A; Jappelli, Roberto; Izpisúa Belmonte, Juan Carlos; Kintner, Chris

    2008-03-15

    The Mesp bHLH genes play a conserved role during segmental patterning of the mesoderm in the vertebrate embryo by specifying segmental boundaries and anteroposterior (A-P) segmental polarity. Here we use a xenotransgenic approach to compare the transcriptional enhancers that drive expression of the Mesp genes within segments of the presomitic mesoderm (PSM) of different vertebrate species. We find that the genomic sequences upstream of the mespb gene in the pufferfish Takifugu rubripes (Tr-mespb) are able to drive segmental expression in transgenic Xenopus embryos while those from the Xenopus laevis mespb (Xl-mespb) gene drive segmental expression in transgenic zebrafish. In both cases, the anterior segmental boundary of transgene expression closely matches the expression of the endogenous Mesp genes, indicating that many inputs into segmental gene expression are highly conserved. By contrast, we find that direct retinoic acid (RA) regulation of endogenous Mesp gene expression is variable among vertebrate species. Both Tr-mespb and Xl-mespb are directly upregulated by RA, through a complex, distal element. By contrast, RA represses the zebrafish Mesp genes. We show that this repression is mediated, in part, by RA-mediated activation of the Ripply genes, which together with Mesp genes form an RA-responsive negative feedback loop. These observations suggest that variations in a direct response to RA input may allow for changes in A-P patterning of the segments in different vertebrate species.

  12. 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

  13. Electromagnetic Steering of a Magnetic Cylindrical Microrobot Using Optical Feedback Closed-Loop Control

    NASA Astrophysics Data System (ADS)

    Ghanbari, Ali; Chang, Pyung H.; Nelson, Bradley J.; Choi, Hongsoo

    2014-04-01

    Control of small magnetic machines in viscous fluids may enable new medical applications of microrobots. Small-scale viscous environments lead to low Reynolds numbers, and although the flow is linear and steady, the magnetic actuation introduces a dynamic response that is nonlinear. We account for these nonlinearities, and the uncertainties in the dynamic and magnetic properties of the microrobot, by using time-delay estimation. The microrobot consists of a cylindrical magnet, 1 mm long and 500 µm in diameter, and is tracked using a visual feedback system. The microrobot was placed in silicone oil with a dynamic viscosity of 1 Pa.s, and followed step inputs with rise times of 0.45 s, 0.51 s, and 1.77 s, and overshoots of 37.5%, 33.3%, and 34.4% in the x, y, and z directions, respectively. In silicone oil with a viscosity of 3 Pa.s, the rise times were 1.04 s, 0.72 s, and 2.19 s, and the overshoots were 47.8%, 48.5%, and 86.8%. This demonstrates that closed-loop control of the magnetic microrobot was better in the less viscous fluid.

  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

    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.

  16. Quantum-enhanced metrology with the single-mode coherent states of an optical cavity inside a quantum feedback loop

    NASA Astrophysics Data System (ADS)

    Clark, Lewis A.; Stokes, Adam; Beige, Almut

    2016-08-01

    In this paper, we use the nonlinear generator of dynamics of the individual quantum trajectories of an optical cavity inside an instantaneous quantum feedback loop to measure the phase shift between two pathways of light with a precision above the standard quantum limit. The feedback laser provides a reference frame and constantly increases the dependence of the state of the resonator on the unknown phase. Since our quantum metrology scheme can be implemented with current technology and does not require highly efficient single photon detectors, it should be of practical interest until highly entangled many-photon states become more readily available.

  17. Coherence enhancement of a chirped DFB laser for frequency-modulated continuous-wave reflectometry using a composite feedback loop.

    PubMed

    Qin, Jie; Zhou, Qian; Xie, Weilin; Xu, Yan; Yu, Shengguo; Liu, Zhangweiyi; Tong, Yi tian; Dong, Yi; Hu, Weisheng

    2015-10-01

    We demonstrate efficient coherence enhancement of a chirped distributed feedback (DFB) laser for frequency-modulated continuous-wave (FMCW) reflectometry. Both sweep nonlinearity and broadband stochastic frequency noises during the laser chirp are efficiently suppressed by a composite feedback loop. The residual frequency error relative to a perfect linear chirp is shown to be about 89 kHz for a laser chirp of 50 GHz in 100 ms, compared with 44 MHz with the loop open. The broadband frequency noise suppression of the frequency-swept laser greatly improves its coherence, leading to a higher signal-to-noise ratio and a significantly extended measurement range in FMCW reflectometry ranging. We demonstrate a 2 mm transform-limited spatial resolution at a range window of 50 m and a 17.5 cm spatial resolution at an extended measurement range of 750 m, which is about 15 times the intrinsic laser round-trip coherence length. PMID:26421566

  18. 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

  19. Highly specific transgene expression mediated by a complex adenovirus vector incorporating a prostate-specific amplification feedback loop

    PubMed Central

    Woraratanadharm, Jan; Rubinchik, Semyon; Yu, Hong; Fan, Fan; Morrow, Scotty M.; Dong., John Y.

    2007-01-01

    Summary Development of novel therapeutic agents is needed to address the problems of locally recurrent, metastatic, and advanced hormone-refractory prostate cancer. We have constructed a novel complex adenovirus (Ad) vector regulation system that incorporates both the prostate-specific ARR2PB promoter and a positive feedback loop using the TRE promoter to enhance gene expression. This regulation strategy involves the incorporation of the TRE upstream of the prostate-specific ARR2PB promoter to enhance its activity with Tet-regulation. The expressions of both GFP and tTA were placed under the control of these TRE-ARR2PB promoters, so that in the cells of prostate origin, a positive feedback loop would be generated. This design greatly enhanced GFP reporter expression in prostate cancer cells, while retaining tight control of expression in non-prostate cancer cells, even at MOI as high as 1000. This novel positive feedback loop with prostate specificity (PFLPS) regulation system we have developed may have broad applications for expressing not only high levels of toxic proteins in cancer cells but alternatively could be manipulated to regulate essential genes in a highly efficient conditionally replicative adenovirus (CRAd) vector specifically directed to prostate cancer cells. The PFLPS regulation system, therefore, serves as a promising new approach in the development of both a specific and effective vector for cancer gene therapy. PMID:15229631

  20. Experimental test of an eco-evolutionary dynamic feedback loop between evolution and population density in the green peach aphid.

    PubMed

    Turcotte, Martin M; Reznick, David N; Daniel Hare, J

    2013-05-01

    An eco-evolutionary feedback loop is defined as the reciprocal impacts of ecology on evolutionary dynamics and evolution on ecological dynamics on contemporary timescales. We experimentally tested for an eco-evolutionary feedback loop in the green peach aphid, Myzus persicae, by manipulating initial densities and evolution. We found strong evidence that initial aphid density alters the rate and direction of evolution, as measured by changes in genotype frequencies through time. We also found that evolution of aphids within only 16 days, or approximately three generations, alters the rate of population growth and predicts density compared to nonevolving controls. The impact of evolution on population dynamics also depended on density. In one evolution treatment, evolution accelerated population growth by up to 10.3% at high initial density or reduced it by up to 6.4% at low initial density. The impact of evolution on population growth was as strong as or stronger than that caused by a threefold change in intraspecific density. We found that, taken together, ecological condition, here intraspecific density, alters evolutionary dynamics, which in turn alter concurrent population growth rate (ecological dynamics) in an eco-evolutionary feedback loop. Our results suggest that ignoring evolution in studies predicting population dynamics might lead us to over- or underestimate population density and that we cannot predict the evolutionary outcome within aphid populations without considering population size.

  1. Influence of the feedback loops in the trp operon of B. subtilis on the system dynamic response and noise amplitude.

    PubMed

    Zamora-Chimal, Criseida; Santillán, Moisés; Rodríguez-González, Jesús

    2012-10-01

    In this paper we introduce a mathematical model for the tryptophan operon regulatory pathway in Bacillus subtilis. This model considers the transcription-attenuation, and the enzyme-inhibition regulatory mechanisms. Special attention is paid to the estimation of all the model parameters from reported experimental data. With the aid of this model we investigate, from a mathematical-modeling point of view, whether the existing multiplicity of regulatory feedback loops is advantageous in some sense, regarding the dynamic response and the biochemical noise in the system. The tryptophan operon dynamic behavior is studied by means of deterministic numeric simulations, while the biochemical noise is analyzed with the aid of stochastic simulations. The model feasibility is tested comparing its stochastic and deterministic results with experimental reports. Our results for the wildtype and for a couple of mutant bacterial strains suggest that the enzyme-inhibition feedback loop, dynamically accelerates the operon response, and plays a major role in the reduction of biochemical noise. Also, the transcription-attenuation feedback loop makes the trp operon sensitive to changes in the endogenous tryptophan level, and increases the amplitude of the biochemical noise.

  2. Influence of the feedback loops in the trp operon of B. subtilis on the system dynamic response and noise amplitude.

    PubMed

    Zamora-Chimal, Criseida; Santillán, Moisés; Rodríguez-González, Jesús

    2012-10-01

    In this paper we introduce a mathematical model for the tryptophan operon regulatory pathway in Bacillus subtilis. This model considers the transcription-attenuation, and the enzyme-inhibition regulatory mechanisms. Special attention is paid to the estimation of all the model parameters from reported experimental data. With the aid of this model we investigate, from a mathematical-modeling point of view, whether the existing multiplicity of regulatory feedback loops is advantageous in some sense, regarding the dynamic response and the biochemical noise in the system. The tryptophan operon dynamic behavior is studied by means of deterministic numeric simulations, while the biochemical noise is analyzed with the aid of stochastic simulations. The model feasibility is tested comparing its stochastic and deterministic results with experimental reports. Our results for the wildtype and for a couple of mutant bacterial strains suggest that the enzyme-inhibition feedback loop, dynamically accelerates the operon response, and plays a major role in the reduction of biochemical noise. Also, the transcription-attenuation feedback loop makes the trp operon sensitive to changes in the endogenous tryptophan level, and increases the amplitude of the biochemical noise. PMID:22713856

  3. 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

  4. 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.

  5. 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.

  6. Tumor Protein p63/Nuclear Factor κB Feedback Loop in Regulation of Cell Death*

    PubMed Central

    Sen, Tanusree; Sen, Nilkantha; Huang, Yiping; Sinha, Debasish; Luo, Zhen-Ge; Ratovitski, Edward A.; Sidransky, David

    2011-01-01

    Tumor protein (TP)-p53 family members often play proapoptotic roles, whereas nuclear factor κB (NF-κB) functions as a proapoptotic and antiapoptotic regulator depending on the cellular environment. We previously showed that the NF-κB activation leads to the reduction of the TP63 isoform, ΔNp63α, thereby rendering the cells susceptible to cell death upon DNA damage. However, the functional relationship between TP63 isotypes and NF-κB is poorly understood. Here, we report that the TAp63 regulates NF-κB transcription and protein stability subsequently leading to the cell death phenotype. We found that TAp63α induced the expression of the p65 subunit of NF-κB (RELA) and target genes involved in cell cycle arrest or apoptosis, thereby triggering cell death pathways in MCF10A cells. RELA was shown to concomitantly modulate specific cell survival pathways, making it indispensable for the TAp63α-dependent regulation of cell death. We showed that TAp63α and RELA formed protein complexes resulted in their mutual stabilization and inhibition of the RELA ubiquitination. Finally, we showed that TAp63α directly induced RelA transcription by binding to and activating of its promoter and, in turn, leading to activation of the NF-κB-dependent cell death genes. Overall, our data defined the regulatory feedback loop between TAp63α and NF-κB involved in the activation of cell death process of cancer cells. PMID:22020940

  7. Optical feedback technique extends frequency response of photoconductors

    NASA Technical Reports Server (NTRS)

    Katzberg, S. J.

    1975-01-01

    Feedback circuit consists of high-gain light-to-voltage converter with frequency-limited nonlinear photoconductor inside feedback loop. Feedback element is visible light-emitting diode with light-out versus current-in characteristic that is linear over several decades.

  8. OncomiR addiction is generated by a miR-155 feedback loop in Theileria-transformed leukocytes.

    PubMed

    Marsolier, Justine; Pineau, Sandra; 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.

  9. 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

  10. 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.

  11. 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.

  12. An Epigenetic Feedback Regulatory Loop Involving MicroRNA-195 and MBD1 Governs Neural Stem Cell Differentiation

    PubMed Central

    Liu, Changmei; Teng, Zhao-Qian; McQuate, Andrea L.; Jobe, Emily M.; Christ, Christa C.; von Hoyningen-Huene, Sergei J.; Reyes, Marie D.; Polich, Eric D.; Xing, Yina; Li, Yue; Guo, Weixiang; Zhao, Xinyu

    2013-01-01

    Background Epigenetic mechanisms, including DNA methylation, histone modification, and microRNAs, play pivotal roles in stem cell biology. Methyl-CpG binding protein 1 (MBD1), an important epigenetic regulator of adult neurogenesis, controls the proliferation and differentiation of adult neural stem/progenitor cells (aNSCs). We recently demonstrated that MBD1 deficiency in aNSCs leads to altered expression of several noncoding microRNAs (miRNAs). Methodology/Principal Findings Here we show that one of these miRNAs, miR-195, and MBD1 form a negative feedback loop. While MBD1 directly represses the expression of miR-195 in aNSCs, high levels of miR-195 in turn repress the expression of MBD1. Both gain-of-function and loss-of-function investigations show that alterations of the MBD1–miR-195 feedback loop tip the balance between aNSC proliferation and differentiation. Conclusions/Significance Therefore the regulatory loop formed by MBD1 and miR-195 is an important component of the epigenetic network that controls aNSC fate. PMID:23349673

  13. The MYB23 gene provides a positive feedback loop for cell fate specification in the Arabidopsis root epidermis.

    PubMed

    Kang, Yeon Hee; Kirik, Victor; Hulskamp, Martin; Nam, Kyoung Hee; Hagely, Katherine; Lee, Myeong Min; Schiefelbein, John

    2009-04-01

    The specification of cell fates during development requires precise regulatory mechanisms to ensure robust cell type patterns. Theoretical models of pattern formation suggest that a combination of negative and positive feedback mechanisms are necessary for efficient specification of distinct fates in a field of differentiating cells. Here, we examine the role of the R2R3-MYB transcription factor gene, AtMYB23 (MYB23), in the establishment of the root epidermal cell type pattern in Arabidopsis thaliana. MYB23 is closely related to, and is positively regulated by, the WEREWOLF (WER) MYB gene during root epidermis development. Furthermore, MYB23 is able to substitute for the function of WER and to induce its own expression when controlled by WER regulatory sequences. We also show that the MYB23 protein binds to its own promoter, suggesting a MYB23 positive feedback loop. The localization of MYB23 transcripts and MYB23-green fluorescent protein (GFP) fusion protein, as well as the effect of a chimeric MYB23-SRDX repressor construct, links MYB23 function to the developing non-hair cell type. Using mutational analyses, we find that MYB23 is necessary for precise establishment of the root epidermal pattern, particularly under conditions that compromise the cell specification process. These results suggest that MYB23 participates in a positive feedback loop to reinforce cell fate decisions and ensure robust establishment of the cell type pattern in the Arabidopsis root epidermis.

  14. Essential role of Bmp signaling and its positive feedback loop in the early cell fate evolution of chordates.

    PubMed

    Kozmikova, Iryna; Candiani, Simona; Fabian, Peter; Gurska, Daniela; Kozmik, Zbynek

    2013-10-15

    In chordates, early separation of cell fate domains occurs prior to the final specification of ectoderm to neural and non-neural as well as mesoderm to dorsal and ventral during development. Maintaining such division with the establishment of an exact border between the domains is required for the formation of highly differentiated structures such as neural tube and notochord. We hypothesized that the key condition for efficient cell fate separation in a chordate embryo is the presence of a positive feedback loop for Bmp signaling within the gene regulatory network (GRN), underlying early axial patterning. Here, we therefore investigated the role of Bmp signaling in axial cell fate determination in amphioxus, the basal chordate possessing a centralized nervous system. Pharmacological inhibition of Bmp signaling induces dorsalization of amphioxus embryos and expansion of neural plate markers, which is consistent with an ancestral role of Bmp signaling in chordate axial patterning and neural plate formation. Furthermore, we provided evidence for the presence of the positive feedback loop within the Bmp signaling network of amphioxus. Using mRNA microinjections we found that, in contrast to vertebrate Vent genes, which promote the expression of Bmp4, amphioxus Vent1 is likely not responsible for activation of cephalochordate ortholog Bmp2/4. Cis-regulatory analysis of amphioxus Bmp2/4, Admp and Chordin promoters in medaka embryos revealed remarkable conservation of the gene regulatory information between vertebrates and basal chordates. Our data suggest that emergence of a positive feedback loop within the Bmp signaling network may represent a key molecular event in the evolutionary history of the chordate cell fate determination.

  15. Essential role of Bmp signaling and its positive feedback loop in the early cell fate evolution of chordates.

    PubMed

    Kozmikova, Iryna; Candiani, Simona; Fabian, Peter; Gurska, Daniela; Kozmik, Zbynek

    2013-10-15

    In chordates, early separation of cell fate domains occurs prior to the final specification of ectoderm to neural and non-neural as well as mesoderm to dorsal and ventral during development. Maintaining such division with the establishment of an exact border between the domains is required for the formation of highly differentiated structures such as neural tube and notochord. We hypothesized that the key condition for efficient cell fate separation in a chordate embryo is the presence of a positive feedback loop for Bmp signaling within the gene regulatory network (GRN), underlying early axial patterning. Here, we therefore investigated the role of Bmp signaling in axial cell fate determination in amphioxus, the basal chordate possessing a centralized nervous system. Pharmacological inhibition of Bmp signaling induces dorsalization of amphioxus embryos and expansion of neural plate markers, which is consistent with an ancestral role of Bmp signaling in chordate axial patterning and neural plate formation. Furthermore, we provided evidence for the presence of the positive feedback loop within the Bmp signaling network of amphioxus. Using mRNA microinjections we found that, in contrast to vertebrate Vent genes, which promote the expression of Bmp4, amphioxus Vent1 is likely not responsible for activation of cephalochordate ortholog Bmp2/4. Cis-regulatory analysis of amphioxus Bmp2/4, Admp and Chordin promoters in medaka embryos revealed remarkable conservation of the gene regulatory information between vertebrates and basal chordates. Our data suggest that emergence of a positive feedback loop within the Bmp signaling network may represent a key molecular event in the evolutionary history of the chordate cell fate determination. PMID:23933491

  16. 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.

  17. 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.

  18. Feedback.

    ERIC Educational Resources Information Center

    Stenstrom, Anna-Brita

    A study of feedback in conversational question-response exchanges focused on the questioner's feedback to the respondent. It examined three types of "followup" moves: the ordinary type revealing the questioner's attitude to the response and closing the exchange; the type signaling the questioner's reaction to the response and inviting further…

  19. 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.

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

    PubMed

    Giacco, Ferdinando; Du, Xueliang; Carratú, 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.

  1. The Dorsal/miR-1959/Cactus feedback loop facilitates the infection of WSSV in Litopenaeus vannamei.

    PubMed

    Xu, Xiaopeng; Yuan, Jia; Yang, Linwei; Weng, Shaoping; He, Jianguo; Zuo, Hongliang

    2016-09-01

    miR-1959, a novel microRNA identified from Litopenaeus vannamei, mediates a positive feedback loop between Dorsal and Cactus that can continuously maintain the activation of the NF-κB pathway. It has been known that miR-1959 is involved in antibacterial immunity in shrimp, but its function in antiviral responses is still unknown. In this study, we focused on the role of miR-1959 in infection of white spot syndrome virus (WSSV), the major viral pathogen in shrimp worldwide. The expression of miR-1959 in shrimp hemocytes, gill, and hepatopancreas was significantly up-regulated upon WSSV infection. Dual-luciferase reporter assays demonstrated that miR-1959 could enhance the activity of the promoter of WSSV immediate early gene ie1. In vivo experiments also showed that inhibition of miR-1959 led to decrease of the mortality of WSSV-infected shrimp and the genome copies of WSSV in tissues, meanwhile the expression of WSSV ie1 and VP28 genes was down-regulated. In contrast, increase of the miR-1959 level in shrimp by injection of miR-1959 mimics produced opposite results. These suggested that the Dorsal/miR-1959/Cactus feedback loop could favor the infection of WSSV in shrimp. Thus, our study helps further reveal the interaction between WSSV and shrimp immune system.

  2. 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

  3. The Dorsal/miR-1959/Cactus feedback loop facilitates the infection of WSSV in Litopenaeus vannamei.

    PubMed

    Xu, Xiaopeng; Yuan, Jia; Yang, Linwei; Weng, Shaoping; He, Jianguo; Zuo, Hongliang

    2016-09-01

    miR-1959, a novel microRNA identified from Litopenaeus vannamei, mediates a positive feedback loop between Dorsal and Cactus that can continuously maintain the activation of the NF-κB pathway. It has been known that miR-1959 is involved in antibacterial immunity in shrimp, but its function in antiviral responses is still unknown. In this study, we focused on the role of miR-1959 in infection of white spot syndrome virus (WSSV), the major viral pathogen in shrimp worldwide. The expression of miR-1959 in shrimp hemocytes, gill, and hepatopancreas was significantly up-regulated upon WSSV infection. Dual-luciferase reporter assays demonstrated that miR-1959 could enhance the activity of the promoter of WSSV immediate early gene ie1. In vivo experiments also showed that inhibition of miR-1959 led to decrease of the mortality of WSSV-infected shrimp and the genome copies of WSSV in tissues, meanwhile the expression of WSSV ie1 and VP28 genes was down-regulated. In contrast, increase of the miR-1959 level in shrimp by injection of miR-1959 mimics produced opposite results. These suggested that the Dorsal/miR-1959/Cactus feedback loop could favor the infection of WSSV in shrimp. Thus, our study helps further reveal the interaction between WSSV and shrimp immune system. PMID:27492121

  4. A regulatory feedback loop between HIF-1α and PIM2 in HepG2 cells.

    PubMed

    Yu, Zhenhai; Zhao, Xiaoping; Ge, Yingying; Zhang, Teng; Huang, Liangqian; Zhou, Xiang; Xie, Lei; Liu, Jianjun; Huang, Gang

    2014-01-01

    To survive under hypoxic conditions, cancer cells remodel glucose metabolism to support tumor progression. HIF transcription factor is essential for cellular response to hypoxia. The underlying mechanism how HIF is constitutively activated in cancer cells remains elusive. In the present study, we characterized a regulatory feedback loop between HIF-1α and PIM2 in HepG2 cells. Serine/threonine kinase proto-oncogene PIM2 level was induced upon hypoxia in a HIF-1α-mediated manner in cancer cells. HIF-1α induced PIM2 expression via binding to the hypoxia-responsive elements (HREs) of the PIM2 promoter. In turn, PIM2 interacted with HIF-1α, especially a transactivation domain of HIF-1α. PIM2 as a co-factor but not an upstream kinase of HIF-1α, enhanced HIF-1α effect in response to hypoxia. The positive feedback loop between PIM2 and HIF-1α was correlated with glucose metabolism as well as cell survival in HepG2 cells. Such a regulatory mode may be important for the adaptive responses of cancer cells in antagonizing hypoxia during cancer progression. PMID:24505470

  5. 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.

  6. Complete low power controller for high voltage power systems

    SciTech Connect

    Sumner, R.; Blanar, G.

    1997-12-31

    The MHV100 is a custom CMOS integrated circuit, developed for the AMS experiment. It provides complete control for a single channel high voltage (HV) generator and integrates all the required digital communications, D to A and A to D converters, the analog feedback loop and output drivers. This chip has been designed for use in both distributed high voltage systems or for low cost single channel high voltage systems. The output voltage and current range is determined by the external components.

  7. 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

  8. 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

  9. 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.

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

    SciTech Connect

    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.

  11. 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.

  12. 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…

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

    NASA Astrophysics Data System (ADS)

    Gaspari, M.

    Supermassive black hole accretion and feedback play central role in the evolution of galaxies, groups, and clusters. I review how AGN feedback is tightly coupled with the formation of multiphase gas and the newly probed chaotic cold accretion (CCA). In a turbulent and heated atmosphere, cold clouds and kpc-scale filaments condense out of the plasma via thermal instability and rain toward the black hole. In the nucleus, the recurrent chaotic collisions between the cold clouds, filaments, and central torus promote angular momentum cancellation or mixing, boosting the accretion rate up to 100 times the Bondi rate. The rapid variability triggers powerful AGN outflows, which quench the cooling flow and star formation without destroying the cool core. The AGN heating stifles the formation of multiphase gas and accretion, the feedback subsides and the hot halo is allowed to cool again, restarting a new cycle. Ultimately, CCA creates a symbiotic link between the black hole and the whole host via a tight self-regulated feedback which preserves the gaseous halo in global thermal equilibrium throughout cosmic time.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Persistent activation of STAT3 by PIM2-driven positive feedback loop for epithelial-mesenchymal transition in breast cancer.

    PubMed

    Uddin, Nizam; Kim, Rae-Kwon; Yoo, Ki-Chun; Kim, Young-Heon; Cui, Yan-Hong; Kim, In-Gyu; Suh, Yongjoon; Lee, Su-Jae

    2015-06-01

    Metastasis of breast cancer is promoted by epithelial-mesenchymal transition (EMT). Emerging evidence suggests that STAT3 is a critical signaling node in EMT and is constitutively activated in many carcinomas, including breast cancer. However, its signaling mechanisms underlying persistent activation of STAT3 associated with EMT remain obscure. Here, we report that PIM2 promotes activation of STAT3 through induction of cytokines. Activation of STAT3 caused an increase in PIM2 expression, implicating a positive feedback loop between PIM2 and STAT3. In agreement, targeting of either PIM2, STAT3 or PIM2-dependent cytokines suppressed EMT-associated migratory and invasive properties through inhibition of ZEB1. Taken together, our findings identify the signaling mechanisms underlying the persistent activation of STAT3 and the oncogenic role of PIM2 in EMT in breast cancer.

  19. Persistent activation of STAT3 by PIM2-driven positive feedback loop for epithelial-mesenchymal transition in breast cancer.

    PubMed

    Uddin, Nizam; Kim, Rae-Kwon; Yoo, Ki-Chun; Kim, Young-Heon; Cui, Yan-Hong; Kim, In-Gyu; Suh, Yongjoon; Lee, Su-Jae

    2015-06-01

    Metastasis of breast cancer is promoted by epithelial-mesenchymal transition (EMT). Emerging evidence suggests that STAT3 is a critical signaling node in EMT and is constitutively activated in many carcinomas, including breast cancer. However, its signaling mechanisms underlying persistent activation of STAT3 associated with EMT remain obscure. Here, we report that PIM2 promotes activation of STAT3 through induction of cytokines. Activation of STAT3 caused an increase in PIM2 expression, implicating a positive feedback loop between PIM2 and STAT3. In agreement, targeting of either PIM2, STAT3 or PIM2-dependent cytokines suppressed EMT-associated migratory and invasive properties through inhibition of ZEB1. Taken together, our findings identify the signaling mechanisms underlying the persistent activation of STAT3 and the oncogenic role of PIM2 in EMT in breast cancer. PMID:25854938

  20. miR-340 and ZEB1 negative feedback loop regulates TGF-β- mediated breast cancer progression

    PubMed Central

    Xie, Ye-Gong; Wang, Jie; Mao, Jie-Fei; Zhang, Bin; Wang, Xin; Cao, Xu-Chen

    2016-01-01

    MicroRNAs act as key regulators in carcinogenesis and progression in various cancers. In present study, we explored the role of miR-340 in the breast cancer progression. Our results showed that overexpression of miR-340 inhibits breast cancer cell proliferation and invasion, whereas depletion of miR-340 promotes breast cancer progression. Molecularly, ZEB1 was identified as a target gene of miR-340 and miR-340 suppressed the expression of ZEB1 by directly binding to the 3′-UTR of ZEB1. Furthermore, ZEB1 transcriptionally suppresses miR-340 expression. The negative feedback loop regulated TGF-β-mediated breast cancer progression. In conclusion, our data suggested that miR-340 acted as a tumor suppressor in breast cancer progression. PMID:27036021

  1. Repression of Essential Chloroplast Genes Reveals New Signaling Pathways and Regulatory Feedback Loops in Chlamydomonas[W

    PubMed Central

    Ramundo, Silvia; Rahire, Michèle; Schaad, Olivier; Rochaix, Jean-David

    2013-01-01

    Although reverse genetics has been used to elucidate the function of numerous chloroplast proteins, the characterization of essential plastid genes and their role in chloroplast biogenesis and cell survival has not yet been achieved. Therefore, we developed a robust repressible chloroplast gene expression system in the unicellular alga Chlamydomonas reinhardtii based mainly on a vitamin-repressible riboswitch, and we used this system to study the role of two essential chloroplast genes: ribosomal protein S12 (rps12), encoding a plastid ribosomal protein, and rpoA, encoding the α-subunit of chloroplast bacterial-like RNA polymerase. Repression of either of these two genes leads to the arrest of cell growth, and it induces a response that involves changes in expression of nuclear genes implicated in chloroplast biogenesis, protein turnover, and stress. This response also leads to the overaccumulation of several plastid transcripts and reveals the existence of multiple negative regulatory feedback loops in the chloroplast gene circuitry. PMID:23292734

  2. 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

  3. 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

  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

    Selitrennik, Michael; Lev, Sima

    2015-09-01

    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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  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. 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

  13. 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.

  14. 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

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

    PubMed Central

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

    2016-01-01

    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

  16. 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

  17. Phytochrome signaling in green Arabidopsis seedlings: impact assessment of a mutually negative phyB-PIF feedback loop.

    PubMed

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

    2012-05-01

    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

  18. Hierarchical scale dependence associated with the extension of the nonlinear feedback loop in a seven-dimensional Lorenz model

    NASA Astrophysics Data System (ADS)

    Shen, Bo-Wen

    2016-07-01

    In this study, we construct a seven-dimensional Lorenz model (7DLM) to discuss the impact of an extended nonlinear feedback loop on solutions' stability and illustrate the hierarchical scale dependence of chaotic solutions. Compared to the 5DLM, the 7DLM includes two additional high wavenumber modes that are selected based on an analysis of the nonlinear temperature advection term, a Jacobian term (J(ψ, θ)), where, ψ and θ represent the streamfunction and temperature perturbations, respectively. Fourier modes that represent temperature in the 7DLM can be categorized into three major scales as the primary (the largest scale), secondary, and tertiary (the smallest scale) modes. Further extension of the nonlinear feedback loop within the 7DLM can provide negative nonlinear feedback to stabilize solutions, thus leading to a much larger critical value for the Rayleigh parameter (rc ˜ 116.9) for the onset of chaos, as compared to an rc of 42.9 for the 5DLM as well as an rc of 24.74 for the 3DLM. The rc is determined by an analysis of ensemble Lyapunov exponents (eLEs) with a Prandtl number (σ) of 10. To examine the dependence of rc on the value of the Prandtl number, a linear stability analysis is performed near the nontrivial critical point using a wide range of the Rayleigh parameter (40 ≤ r ≤ 195) and the Prandtl number (5 ≤ σ ≤ 25). Then an eLE analysis is conducted using selected values of the Prandtl number. The linear stability analysis is done by solving for the analytical solutions of the critical points, by linearizing the 7DLM with respect to the analytical solutions, and by calculating the eigenvalues of the linearized system. Within the range of (5 ≤ σ ≤ 25), the 7DLM requires a larger rc for the onset of chaos than the 5DLM. In addition to the negative nonlinear feedback illustrated and emulated by the quasi-equilibrium state solutions for high wavenumber modes, the 7DLM reveals the hierarchical scale dependence of chaotic solutions. For

  19. A double-negative feedback loop between E2F3b and miR- 200b regulates docetaxel chemosensitivity of human lung adenocarcinoma cells

    PubMed Central

    Gao, Yanping; Chen, Longbang; Song, Haizhu; Chen, Yitian; Wang, Rui; Feng, Bing

    2016-01-01

    MicroRNAs (miRNAs) are non-coding small RNAs which negatively regulate gene expressions mainly through 3′-untranslated region (3′-UTR) binding of target mRNAs. Recent studies have highlighted the feedback loops between miRNAs and their target genes in physiological and pathological processes including chemoresistance of cancers. Our previous study identified miR-200b/E2F3 axis as a chemosensitivity restorer of human lung adenocarcinoma (LAD) cells. Moreover, E2F3b was bioinformatically proved to be a potential transcriptional regulator of pre-miR-200b gene promoter. The existance of this double-negative feedback minicircuitry comprising E2F3b and miR-200b was confirmed by chromatin immunoprecipitation (ChIP) assay, site-specific mutation and luciferase reporter assay. And the underlying regulatory mechanisms of this feedback loop on docetaxel resistance of LAD cells were further investigated by applying in vitro chemosensitivity assay, colony formation assay, flow cytometric analysis of cell cycle and apoptosis, as well as mice xenograft model. In conclusion, our results suggest that the double-negative feedback loop between E2F3b and miR-200b regulates docetaxel chemosensitivity of human LAD cells mainly through cell proliferation, cell cycle distribution and apoptosis. PMID:27027446

  20. 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 β-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 β-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 β-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.

  1. Ecological consequences of body size decline in harvested fish species: positive feedback loops in trophic interactions amplify human impact.

    PubMed

    Audzijonyte, Asta; Kuparinen, Anna; Gorton, Rebecca; Fulton, Elizabeth A

    2013-04-23

    Humans are changing marine ecosystems worldwide, both directly through fishing and indirectly through climate change. One of the little explored outcomes of human-induced change involves the decreasing body sizes of fishes. We use a marine ecosystem model to explore how a slow (less than 0.1% per year) decrease in the length of five harvested species could affect species interactions, biomasses and yields. We find that even small decreases in fish sizes are amplified by positive feedback loops in the ecosystem and can lead to major changes in natural mortality. For some species, a total of 4 per cent decrease in length-at-age over 50 years resulted in 50 per cent increase in predation mortality. However, the magnitude and direction in predation mortality changes differed among species and one shrinking species even experienced reduced predation pressure. Nevertheless, 50 years of gradual decrease in body size resulted in 1-35% decrease in biomasses and catches of all shrinking species. Therefore, fisheries management practices that ignore contemporary life-history changes are likely to overestimate long-term yields and can lead to overfishing. PMID:23365151

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

    PubMed Central

    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

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

    PubMed

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

    2015-11-01

    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

  4. 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

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

    PubMed

    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

    2014-12-16

    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

  6. Lipocalin 2 promotes the migration and invasion of esophageal squamous cell carcinoma cells through a novel positive feedback loop.

    PubMed

    Du, Ze-Peng; Wu, Bing-Li; Xie, Yang-Min; Zhang, Ying-Li; Liao, Lian-Di; Zhou, Fei; Xie, Jian-Jun; Zeng, Fa-Min; Xu, Xiu-E; Fang, Wang-Kai; Li, En-Min; Xu, Li-Yan

    2015-10-01

    Lipocalin 2 (LCN2) is a poor prognostic factor in esophageal squamous cell carcinoma (ESCC), however its functional roles and molecular mechanisms of action remain to be clarified. Here, we described the functions and signaling pathways for LCN2 in ESCC. Overexpression of LCN2 in ESCC cells accelerated cell migration and invasion in vitro, and promoted lung metastasis in vivo. Blocking LCN2 expression inhibited its pro-oncogenic effect. Either overexpression of LCN2 or treatment with recombinant human LCN2 protein enhanced the activation of MEK/ERK pathway, which in turn increases endogenous LCN2 to increase MMP-9 activity. The decreased p-cofilin and increased p-ERM induced by pERK1/2 cause the cytoskeleton F-actin rearrangement and alter the behavior of ESCC cells mediated by LCN2. As a consequence, activation of MMP-9 and the rearrangement of F-actin throw light on the mechanisms for LCN2 in ESCC. These results imply that LCN2 promotes the migration and invasion of ESCC cells through a novel positive feedback loop.

  7. 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.

  8. 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.

  9. Ecological consequences of body size decline in harvested fish species: positive feedback loops in trophic interactions amplify human impact.

    PubMed

    Audzijonyte, Asta; Kuparinen, Anna; Gorton, Rebecca; Fulton, Elizabeth A

    2013-04-23

    Humans are changing marine ecosystems worldwide, both directly through fishing and indirectly through climate change. One of the little explored outcomes of human-induced change involves the decreasing body sizes of fishes. We use a marine ecosystem model to explore how a slow (less than 0.1% per year) decrease in the length of five harvested species could affect species interactions, biomasses and yields. We find that even small decreases in fish sizes are amplified by positive feedback loops in the ecosystem and can lead to major changes in natural mortality. For some species, a total of 4 per cent decrease in length-at-age over 50 years resulted in 50 per cent increase in predation mortality. However, the magnitude and direction in predation mortality changes differed among species and one shrinking species even experienced reduced predation pressure. Nevertheless, 50 years of gradual decrease in body size resulted in 1-35% decrease in biomasses and catches of all shrinking species. Therefore, fisheries management practices that ignore contemporary life-history changes are likely to overestimate long-term yields and can lead to overfishing.

  10. Feedback Loop of Data Infilling Using Model Result of Actual Evapotranspiration from Satellites and Hydrological Model

    NASA Astrophysics Data System (ADS)

    Murdi Hartanto, Isnaeni; Alexandridis, Thomas K.; van Andel, Schalk Jan; Solomatine, Dimitri

    2014-05-01

    Using satellite data in a hydrological model has long been occurring in modelling of hydrological processes, as a source of low cost regular data. The methods range from using satellite products as direct input, model validation, and data assimilation. However, the satellite data frequently face the missing value problem, whether due to the cloud cover or the limited temporal coverage. The problem could seriously affect its usefulness in hydrological model, especially if the model uses it as direct input, so data infilling becomes one of the important parts in the whole modelling exercise. In this research, actual evapotranspiration product from satellite is directly used as input into a spatially distributed hydrological model, and validated by comparing the catchment's end discharge with measured data. The instantaneous actual evapotranspiration is estimated from MODIS satellite images using a variation of the energy balance model for land (SEBAL). The eight-day cumulative actual evapotranspiration is then obtained by a temporal integration that uses the reference evapotranspiration calculated from meteorological data [1]. However, the above method cannot fill in a cell if the cell is constantly having no-data value during the eight-day periods. The hydrological model requires full set of data without no-data cells, hence, the no-data cells in the satellite's evapotranspiration map need to be filled in. In order to fills the no-data cells, an output of hydrological model is used. The hydrological model is firstly run with reference evapotranspiration as input to calculate discharge and actual evapotranspiration. The no-data cells in the eight-day cumulative map from the satellite are then filled in with the output of the first run of hydrological model. The final data is then used as input in a hydrological model to calculate discharge, thus creating a loop. The method is applied in the case study of Rijnland, the Netherlands where in the winter, cloud cover is

  11. Energy-aware feedback control for a H.264 video decoder

    NASA Astrophysics Data System (ADS)

    Durand, Sylvain; Alt, Anne-Marie; Simon, Daniel; Marchand, Nicolas

    2015-06-01

    Embedded devices using highly integrated chips must cope with conflicting constraints, while executing computationally demanding applications under limited energy storage. Automatic control and feedback loops appear to be an effective solution to simultaneously accommodate for performance uncertainties due to the tiny scale gates variability, varying and poorly predictable computing demands and limited energy storage constraints. This paper presents the example of an embedded video decoder controlled by several feedback loops to carry out the trade-off between decoding quality and energy consumption, exploiting the frequency and voltage scaling capabilities of the chip. The inner loop controls the dynamic voltage and frequency scaling through a fast predictive control strategy. The outer loop computes the scheduling set-points needed by the inner loop to process frames decoding. The feedback loops have been implemented on a stock PC and experimental results are provided.

  12. Performance Comparison of BPL, EtherLoop and SHDSL technology performance on existing pilot cable circuits under the presence of induced voltage

    NASA Astrophysics Data System (ADS)

    Che, Y. X.; Ong, H. S.; Lai, L. C.; Karuppiah, S.; Ong, X. J.; Do, N. Q.

    2013-06-01

    Pilot cable is originally used for utility protection. Then, pilot cable is further utilized for SCADA communication with low frequency PSK modem in the early 1990. However, the quality of pilot cable communication drops recently. Pilot cable starts to deteriorate due to aging and other unknown factors. It is also believed that the presence of induced voltage causes interference to existing modem communication which operates at low frequency channel. Therefore, BPL (Broadband Power Line), EtherLoop and SHDSL (Symmetrical High-speed Digital Subscriber Line) modem technology are proposed as alternative communication solutions for pilot cable communication. The performance of the 3 selected technologies on existing pilot cable circuits under the presence of induced voltage are measured and compared. Total of 11 pilot circuits with different length and level of induced voltage influence are selected for modem testing. The performance of BPL, EtherLoop and SHDSL modem technology are measured by the delay, bandwidth, packet loss and the long term usability SCADA (Supervisory Control and Data Acquisition) application. The testing results are presented and discussed in this paper. The results show that the 3 selected technologies are dependent on distance and independent on the level of induced voltage.

  13. Evidence for an inhibitory feedback loop regulating simian virus 40 large T-antigen fusion protein nuclear transport.

    PubMed Central

    Seydel, U; Jans, D A

    1996-01-01

    Nuclear protein import is central to eukaryotic cell function. It is dependent on ATP, temperature and cytosolic factors, and requires specific targeting sequences called nuclear localization signals (NLSs). Nuclear import kinetics was studied in vitro using digitonin-permeabilized cells of the HTC rat hepatoma cell line and a fluorescently labelled beta-galactosidase fusion protein carrying amino acids 111-135 of the simian virus 40 large T-antigen (T-ag), including the NLS. Nuclear accumulation was rapid, reaching steady-state after about 80 min at 37 degrees C (t1/2 at about 17 min). Surprisingly, maximal nuclear concentration was found to be directly proportional to the concentration of the cytosolic extract and of cytoplasmic T-ag protein. Neither preincubation of cells for 1 h at 37 degrees C before the addition of T-ag protein nor the addition of fresh transport medium after 1 h and continuation of the incubation for another hour affected the maximal nuclear concentration. If cells were allowed to accumulate T-ag protein for 1 h before the addition of fresh transport medium containing different concentrations of T-ag protein and incubated for a further hour, the maximal nuclear concentration did not change unless the concentration of T-ag protein in the second transport mixture exceeded that in the first, in which case the nuclear concentration increased. Nuclear import of T-ag thus appeared (i) to be strictly unidirectional over 2 h at 37 degrees C and (ii) to be regulated by an inhibitory feedback loop, whereby the cytosolic concentration of protein appears to determine directly the precise end point of nuclear accumulation. This study represents the first characterization of this previously undescribed mechanism of regulation of nuclear protein import. PMID:8670127

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. FRET imaging and statistical signal processing reveal positive and negative feedback loops regulating the morphology of randomly migrating HT-1080 cells.

    PubMed

    Kunida, Katsuyuki; Matsuda, Michiyuki; Aoki, Kazuhiro

    2012-05-15

    Cell migration plays an important role in many physiological processes. Rho GTPases (Rac1, Cdc42, RhoA) and phosphatidylinositols have been extensively studied in directional cell migration. However, it remains unclear how Rho GTPases and phosphatidylinositols regulate random cell migration in space and time. We have attempted to address this issue using fluorescence resonance energy transfer (FRET) imaging and statistical signal processing. First, we acquired time-lapse images of random migration of HT-1080 fibrosarcoma cells expressing FRET biosensors of Rho GTPases and phosphatidyl inositols. We developed an image-processing algorithm to extract FRET values and velocities at the leading edge of migrating cells. Auto- and cross-correlation analysis suggested the involvement of feedback regulations among Rac1, phosphatidyl inositols and membrane protrusions. To verify the feedback regulations, we employed an acute inhibition of the signaling pathway with pharmaceutical inhibitors. The inhibition of actin polymerization decreased Rac1 activity, indicating the presence of positive feedback from actin polymerization to Rac1. Furthermore, treatment with PI3-kinase inhibitor induced an adaptation of Rac1 activity, i.e. a transient reduction of Rac1 activity followed by recovery to the basal level. In silico modeling that reproduced the adaptation predicted the existence of a negative feedback loop from Rac1 to actin polymerization. Finally, we identified MLCK as the probable controlling factor in the negative feedback. These findings quantitatively demonstrate positive and negative feedback loops that involve actin, Rac1 and MLCK, and account for the ordered patterns of membrane dynamics observed in randomly migrating cells.

  2. A Current-Mode Buck DC-DC Converter with Frequency Characteristics Independent of Input and Output Voltages Using a Quadratic Compensation Slope

    NASA Astrophysics Data System (ADS)

    Sai, Toru; Sugimoto, Yasuhiro

    By using a quadratic compensation slope, a CMOS current-mode buck DC-DC converter with constant frequency characteristics over wide input and output voltage ranges has been developed. The use of a quadratic slope instead of a conventional linear slope makes both the damping factor in the transfer function and the frequency bandwidth of the current feedback loop independent of the converter's output voltage settings. When the coefficient of the quadratic slope is chosen to be dependent on the input voltage settings, the damping factor in the transfer function and the frequency bandwidth of the current feedback loop both become independent of the input voltage settings. Thus, both the input and output voltage dependences in the current feedback loop are eliminated, the frequency characteristics become constant, and the frequency bandwidth is maximized. To verify the effectiveness of a quadratic compensation slope with a coefficient that is dependent on the input voltage in a buck DC-DC converter, we fabricated a test chip using a 0.18µm high-voltage CMOS process. The evaluation results show that the frequency characteristics of both the total feedback loop and the current feedback loop are constant even when the input and output voltages are changed from 2.5V to 7V and from 0.5V to 5.6V, respectively, using a 3MHz clock.

  3. EMG spike time difference based feedback control.

    PubMed

    Butala, Jaydrath; Arkles, Anthony; Gray, John R

    2007-01-01

    Flight control in insects has been studied extensively; however the underlying neural mechanisms are not fully understood. Output from the central nervous system (CNS) must drive wing phase shifts and flight muscle depressor asymmetries associated with adaptive flight maneuvers. These maneuvers will, in turn, influence the insect's sensory environment, thus closing the feedback loop. We present a novel method that utilizes asymmetrical timing of bilateral depressor muscles, the forewing first basalars (m97), of the locust to close a visual feedback loop in a computer-generated flight simulator. The method converts the time difference between left and right m97s to analog voltage values. These voltage values can be obtained using open-loop experiments (visual motion controlled by the experimenter), or can be used to control closed-loop experiments (muscle activity controls the visual stimuli) experiments. Electromyographic (EMG) signals were obtained from right and left m97 muscles; spike time difference between them was calculated and converted to voltage values. Testing this circuit with real animals, we were able to detect the spike time difference and convert that to voltage that controlled the presentation of a stimulus in a closed-loop environment. This method may be used in conjunction with the flight simulator to understand the manner in which sensory information is integrated with the activity of the flight circuitry to study the neural control of this complex behaviour. PMID:18003414

  4. Feedback control of combustion instabilities from within limit cycle oscillations using H∞ loop-shaping and the ν-gap metric

    NASA Astrophysics Data System (ADS)

    Li, Jingxuan; Morgans, Aimee S.

    2016-07-01

    Combustion instabilities arise owing to a two-way coupling between acoustic waves and unsteady heat release. Oscillation amplitudes successively grow, until nonlinear effects cause saturation into limit cycle oscillations. Feedback control, in which an actuator modifies some combustor input in response to a sensor measurement, can suppress combustion instabilities. Linear feedback controllers are typically designed, using linear combustor models. However, when activated from within limit cycle, the linear model is invalid, and such controllers are not guaranteed to stabilize. This work develops a feedback control strategy guaranteed to stabilize from within limit cycle oscillations. A low-order model of a simple combustor, exhibiting the essential features of more complex systems, is presented. Linear plane acoustic wave modelling is combined with a weakly nonlinear describing function for the flame. The latter is determined numerically using a level set approach. Its implication is that the open-loop transfer function (OLTF) needed for controller design varies with oscillation level. The difference between the mean and the rest of the OLTFs is characterized using the ν-gap metric, providing the minimum required `robustness margin' for an H∞ loop-shaping controller. Such controllers are designed and achieve stability both for linear fluctuations and from within limit cycle oscillations.

  5. Feedback control of combustion instabilities from within limit cycle oscillations using H∞ loop-shaping and the ν-gap metric

    PubMed Central

    Morgans, Aimee S.

    2016-01-01

    Combustion instabilities arise owing to a two-way coupling between acoustic waves and unsteady heat release. Oscillation amplitudes successively grow, until nonlinear effects cause saturation into limit cycle oscillations. Feedback control, in which an actuator modifies some combustor input in response to a sensor measurement, can suppress combustion instabilities. Linear feedback controllers are typically designed, using linear combustor models. However, when activated from within limit cycle, the linear model is invalid, and such controllers are not guaranteed to stabilize. This work develops a feedback control strategy guaranteed to stabilize from within limit cycle oscillations. A low-order model of a simple combustor, exhibiting the essential features of more complex systems, is presented. Linear plane acoustic wave modelling is combined with a weakly nonlinear describing function for the flame. The latter is determined numerically using a level set approach. Its implication is that the open-loop transfer function (OLTF) needed for controller design varies with oscillation level. The difference between the mean and the rest of the OLTFs is characterized using the ν-gap metric, providing the minimum required ‘robustness margin’ for an H∞ loop-shaping controller. Such controllers are designed and achieve stability both for linear fluctuations and from within limit cycle oscillations. PMID:27493558

  6. Frequency- and intensity-noise suppression in Yb3+-doped single-frequency fiber laser by a passive optical-feedback loop.

    PubMed

    Hou, Yubin; Zhang, Qian; Wang, Pu

    2016-06-13

    The frequency and intensity noise of an Yb3+-doped single-frequency distributed Bragg reflector (DBR) fiber laser are effectively reduced by a simple, passive optical-feedback loop (POFL), which consists of only two optical couplers. The feedback loop, which has resonance with the high reflective grating of the DBR laser and relative long optical path compared to the DBR cavity, results in narrower linewidth and lower relative intensity noise (RIN) in the feedback signal. The RIN of relaxation oscillation is reduced by 20dB from -99.9dB/Hz @ 993 kHz to -119.4dB/Hz @ 192 kHz, and the frequency noise was suppressed at frequencies higher than 1 kHz, with a maximum reduction of about 30 dB from 10 kHz to 100 kHz, which results in a spectral linewidth compression from 3.96 kHz to 540 Hz. Even after one fiber amplification stage, the noise did not increase significantly, and a spectral linewidth well below 1 kHz were also achieved at output power of 10W. PMID:27410318

  7. A Repertoire of MicroRNAs Regulates Cancer Cell Starvation by Targeting Phospholipase D in a Feedback Loop That Operates Maximally in Cancer Cells

    PubMed Central

    Fite, Kristen; Elkhadragy, Lobna

    2016-01-01

    We report a negative feedback loop between the signaling protein phospholipase D (PLD), phosphatidic acid (PA), and a specific set of microRNAs (miRNAs) during nutrient starvation of breast cancer cells. We show that PLD expression is increased in four breast cancer cell lines and that hypoxia, cell overcrowding, and nutrient starvation for 3 to 6 h increase expression even further. However, after prolonged (>12-h) starvation, PLD levels return to basal or lower levels. The mechanism for this is as follows. First, during initial starvation, an elevated PA (the product of PLD enzymatic activity) activates mTOR and S6K, known to inhibit apoptosis, and enhances cell migration especially in post-epithelial-to-mesenchymal transition (post-EMT) cancer cells. Second, continued PA production in later starvation induces expression of PLD-targeting microRNA 203 (miR-203), miR-887, miR-3619-5p, and miR-182, which reduce PLD translation. We provide direct evidence for a feedback loop, whereby PLD induction upon starvation leads to PA, which induces expression of miRNAs, which in turn inhibits PLD2 translation. The physiological relevance for breast cancer cells is that as PA can activate cell invasion, then, due to the negative feedback, it can deprive mTOR and S6K of their natural activator. It can further prevent inhibition of apoptosis and allow cells to survive nutrient deprivation, which normal cells cannot do. PMID:26787840

  8. 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.

  9. 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.

  10. A Costas loop with tangent error signal for use in Navstar GPS avionics

    NASA Technical Reports Server (NTRS)

    Painter, J. H.; Mcclung, D. A.; Reininger, R. C.

    1978-01-01

    This paper describes an augmented Costas loop for use in low-cost avionics for the Navstar Global Positioning System. A standard loop has been augmented with supplementing feed-back to give a tracking error voltage proportional to the tangent of the phase error, rather than to the sine. The augmented loop yields increased performance in the presence of input phase acceleration and jerk, as caused by maneuvers of the GPS user vehicle. Many Monte Carlo simulation results are given.

  11. Compensation or Restoration: Closed-Loop Feedback of Movement Quality for Assisted Reach-to-Grasp Exercises with a Multi-Joint Arm Exoskeleton.

    PubMed

    Grimm, Florian; Naros, Georgios; Gharabaghi, Alireza

    2016-01-01

    Assistive technology allows for intensive practice and kinematic measurements during rehabilitation exercises. More recent approaches attach a gravity-compensating multi-joint exoskeleton to the upper extremity to facilitate task-oriented training in three-dimensional space with virtual reality feedback. The movement quality, however, is mostly captured through end-point measures that lack information on proximal inter-joint coordination. This limits the differentiation between compensation strategies and genuine restoration both during the exercise and in the course of rehabilitation. We extended in this proof-of-concept study a commercially available seven degree-of-freedom arm exoskeleton by using the real-time sensor data to display a three-dimensional multi-joint visualization of the user's arm. Ten healthy subjects and three severely affected chronic stroke patients performed reach-to-grasp exercises resembling activities of daily living assisted by the attached exoskeleton and received closed-loop online feedback of the three-dimensional movement in virtual reality. Patients in this pilot study differed significantly with regard to motor performance (accuracy, temporal efficiency, range of motion) and movement quality (proximal inter-joint coordination) from the healthy control group. In the course of 20 training and feedback sessions over 4 weeks, these pathological measures improved significantly toward the reference parameters of healthy participants. It was moreover feasible to capture the evolution of movement pattern kinematics of the shoulder and elbow and to quantify the individual degree of natural movement restoration for each patient. The virtual reality visualization and closed-loop feedback of joint-specific movement kinematics makes it possible to detect compensation strategies and may provide a tool to achieve the rehabilitation goals in accordance with the individual capacity for genuine functional restoration; a proposal that warrants

  12. Compensation or Restoration: Closed-Loop Feedback of Movement Quality for Assisted Reach-to-Grasp Exercises with a Multi-Joint Arm Exoskeleton

    PubMed Central

    Grimm, Florian; Naros, Georgios; Gharabaghi, Alireza

    2016-01-01

    Assistive technology allows for intensive practice and kinematic measurements during rehabilitation exercises. More recent approaches attach a gravity-compensating multi-joint exoskeleton to the upper extremity to facilitate task-oriented training in three-dimensional space with virtual reality feedback. The movement quality, however, is mostly captured through end-point measures that lack information on proximal inter-joint coordination. This limits the differentiation between compensation strategies and genuine restoration both during the exercise and in the course of rehabilitation. We extended in this proof-of-concept study a commercially available seven degree-of-freedom arm exoskeleton by using the real-time sensor data to display a three-dimensional multi-joint visualization of the user's arm. Ten healthy subjects and three severely affected chronic stroke patients performed reach-to-grasp exercises resembling activities of daily living assisted by the attached exoskeleton and received closed-loop online feedback of the three-dimensional movement in virtual reality. Patients in this pilot study differed significantly with regard to motor performance (accuracy, temporal efficiency, range of motion) and movement quality (proximal inter-joint coordination) from the healthy control group. In the course of 20 training and feedback sessions over 4 weeks, these pathological measures improved significantly toward the reference parameters of healthy participants. It was moreover feasible to capture the evolution of movement pattern kinematics of the shoulder and elbow and to quantify the individual degree of natural movement restoration for each patient. The virtual reality visualization and closed-loop feedback of joint-specific movement kinematics makes it possible to detect compensation strategies and may provide a tool to achieve the rehabilitation goals in accordance with the individual capacity for genuine functional restoration; a proposal that warrants

  13. Compensation or Restoration: Closed-Loop Feedback of Movement Quality for Assisted Reach-to-Grasp Exercises with a Multi-Joint Arm Exoskeleton.

    PubMed

    Grimm, Florian; Naros, Georgios; Gharabaghi, Alireza

    2016-01-01

    Assistive technology allows for intensive practice and kinematic measurements during rehabilitation exercises. More recent approaches attach a gravity-compensating multi-joint exoskeleton to the upper extremity to facilitate task-oriented training in three-dimensional space with virtual reality feedback. The movement quality, however, is mostly captured through end-point measures that lack information on proximal inter-joint coordination. This limits the differentiation between compensation strategies and genuine restoration both during the exercise and in the course of rehabilitation. We extended in this proof-of-concept study a commercially available seven degree-of-freedom arm exoskeleton by using the real-time sensor data to display a three-dimensional multi-joint visualization of the user's arm. Ten healthy subjects and three severely affected chronic stroke patients performed reach-to-grasp exercises resembling activities of daily living assisted by the attached exoskeleton and received closed-loop online feedback of the three-dimensional movement in virtual reality. Patients in this pilot study differed significantly with regard to motor performance (accuracy, temporal efficiency, range of motion) and movement quality (proximal inter-joint coordination) from the healthy control group. In the course of 20 training and feedback sessions over 4 weeks, these pathological measures improved significantly toward the reference parameters of healthy participants. It was moreover feasible to capture the evolution of movement pattern kinematics of the shoulder and elbow and to quantify the individual degree of natural movement restoration for each patient. The virtual reality visualization and closed-loop feedback of joint-specific movement kinematics makes it possible to detect compensation strategies and may provide a tool to achieve the rehabilitation goals in accordance with the individual capacity for genuine functional restoration; a proposal that warrants

  14. Multiple feedback control apparatus for power conditioning equipment

    NASA Technical Reports Server (NTRS)

    Biess, John (Inventor); Yu, Yuan (Inventor)

    1977-01-01

    An improved feedback control system to govern the cyclic operation of the power switch of a non-dissipative power conditioning equipment. The apparatus includes two or three control loops working in unison. The first causes the output DC level to be compared with a reference, and the error amplified for control purposes. The second utilizes the AC component of the voltage across the output filter inductor or the current through the output filter capacitor, and the third loop senses the output transients.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. The effects of cascade length, kinetics and feedback loops on biological signal transduction dynamics in a simplified cascade model

    NASA Astrophysics Data System (ADS)

    Qu, Zhilin; Vondriska, Thomas M

    2009-03-01

    How intracellular signals are propagated with appropriate strength, duration and fidelity over time is poorly understood. To address these issues, intracellular signal transduction was studied both analytically and numerically using a simplified cascade model. The main observations can be summarized as follows: when the response kinetics is of the Michaelis-Menten type, the signal strength will always reach the same magnitude as the cascade length increases, regardless of the type of stimulus applied (i.e. either continuous or unitary pulse). However, when the response kinetics is of the Hill type (Hill coefficient >1), there exists a stimulation threshold. If the stimulus is below the threshold, the signal decays toward zero; in contrast, if the stimulus is above the threshold, the signal amplitude reaches a nonzero steady state. The time taken for the signal to proceed through the cascade increases as the half-maximum point, or Hill coefficient, increases, whereas the duration of the output signal at the end of the cascade decreases as the half-maximum point increases. In the presence of positive feedback, the stimulation threshold increases; under these conditions, the feedback strength necessary for bistability changes (with power-law characteristics) inversely related to the length of the cascade. In the presence of negative feedback, oscillations are induced when the Hill coefficient is greater than 1 and the cascade has more than two steps. Likewise, the feedback strength required to generate oscillations changes (again with power-law characteristics) inversely with the length of the cascade.

  1. Optical fiber feedback SQUID magnetometer

    SciTech Connect

    Naito, S.; Sampei, Y.; Takahashi, T. )

    1989-04-01

    This paper describes an optical fiber feedback superconducting quantum interference device (SQUID) magnetometer which was developed to improve electromagnetic interference characteristics. The SQUID consists of an RF SQUID probe, an RF amplifier, two multimode fibers, and a SQUID control unit. Phase-locked pulse width modulation (PWM) was used to construct a flux locked loop (FLL) circuit in the SQUID control unit. The operation of the optical fiber feedback SQUID is stable when a common mode voltage of ac 100 V/50 Hz is applied. It has an energy resolution of 1 x 10/sup -28/ J/Hz. This paper also describes the measurement of an auditory evoked field from the human brain in a magnetically shielded room using the fiber feedback SQUID with a gradiometer type pickup coil.

  2. 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

  3. miR-326-histone deacetylase-3 feedback loop regulates the invasion and tumorigenic and angiogenic response to anti-cancer drugs.

    PubMed

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

    2014-10-01

    Histone modification is known to be associated with multidrug resistance phenotypes. Cancer cell lines that are resistant or have been made resistant to anti-cancer drugs showed lower expression levels of histone deacetylase-3 (HDAC3), among the histone deacetylase(s), than cancer cell lines that were sensitive to anti-cancer drugs. Celastrol and Taxol decreased the expression of HDAC3 in cancer cell lines sensitive to anti-cancer drugs. HDAC3 negatively regulated the invasion, migration, and anchorage-independent growth of cancer cells. HDAC3 conferred sensitivity to anti-cancer drugs in vitro and in vivo. TargetScan analysis predicted miR-326 as a negative regulator of HDAC3. ChIP assays and luciferase assays showed a negative feedback loop between HDAC3 and miR-326. miR-326 decreased the apoptotic effect of anti-cancer drugs, and the miR-326 inhibitor increased the apoptotic effect of anti-cancer drugs. miR-326 enhanced the invasion and migration potential of cancer cells. The miR-326 inhibitor negatively regulated the tumorigenic, metastatic, and angiogenic potential of anti-cancer drug-resistant cancer cells. HDAC3 showed a positive feedback loop with miRNAs such as miR-200b, miR-217, and miR-335. miR-200b, miR-217, and miR-335 negatively regulated the expression of miR-326 and the invasion and migration potential of cancer cells while enhancing the apoptotic effect of anti-cancer drugs. TargetScan analysis predicted miR-200b and miR-217 as negative regulators of cancer-associated gene, a cancer/testis antigen, which is known to regulate the response to anti-cancer drugs. HDAC3 and miR-326 acted upstream of the cancer-associated gene. Thus, we show that the miR-326-HDAC3 feedback loop can be employed as a target for the development of anti-cancer therapeutics.

  4. 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.

  5. 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.

  6. BK channel activation by tungstate requires the β1 subunit extracellular loop residues essential to modulate voltage sensor function and channel gating.

    PubMed

    Fernández-Mariño, Ana I; Valverde, Miguel A; Fernández-Fernández, José M

    2014-07-01

    Tungstate, a compound with antidiabetic, antiobesity, and antihypertensive properties, activates the large-conductance voltage- and Ca(2+)-dependent K(+) (BK) channel containing either β1 or β4 subunits. The BK activation by tungstate is Mg(2+)-dependent and promotes arterial vasodilation, but only in precontracted mouse arteries expressing β1. In this study, we further explored how the β1 subunit participates in tungstate activation of BK channels. Activation of heterologously expressed human BKαβ1 channels in inside-out patches is fully dependent on the Mg(2+) sensitivity of the BK α channel subunit even at high (10 μM) cytosolic Ca(2+) concentration. Alanine mutagenesis of β1 extracellular residues Y74 or S104, which destabilize the active voltage sensor, greatly decreased the tungstate-induced left-shift of the BKαβ1 G-V curves in either the absence or presence of physiologically relevant cytosolic Ca(2+) levels (10 μM). The weakened tungstate activation of the BKαβ1Y74A and BKαβ1S104A mutant channels was not related to decreased Mg(2+) sensitivity. These results, together with previously published reports, support the idea that the putative binding site for tungstate-mediated BK channel activation is located in the pore-forming α channel subunit, around the Mg(2+) binding site. The role of β1 in tungstate-induced channel activation seems to rely on its interaction with the BK α subunit to modulate channel activity. Loop residues that are essential for the regulation of voltage sensor activation and gating of the BK channel are also relevant for BK activation by tungstate.

  7. A conserved threonine in the S1-S2 loop of KV7.2 and K V7.3 channels regulates voltage-dependent activation.

    PubMed

    Füll, Yvonne; Seebohm, Guiscard; Lerche, Holger; Maljevic, Snezana

    2013-06-01

    The voltage-gated potassium channels KV7.2 and KV7.3 (KCNQ2/3 genes) play an important role in regulating neuronal excitability. More than 50 KCNQ2/3 mutations have been identified to cause an inherited form of epilepsy in newborns. For two of those (E119G and S122L) found in the S1-S2 region of KV7.2, we previously showed a decreased channel availability mainly at action potential subthreshold voltages caused by a slight depolarizing shift of the activation curve. Interestingly, recent studies revealed that a threonine residue within the S1-S2 loop, highly conserved among different classes of KV channels, is crucial for both their function and surface expression. To investigate the functional role of the homologous threonine residues in KV7.2 (T114) and KV7.3 (T144) channels, we replaced them with alanine and examined the electrophysiological properties using heterologous expression in CHO cells and whole cell patch clamping. Channels comprising mutant subunits yielded decreased potassium currents with slowed activation and accelerated deactivation kinetics. However, the most striking effect was a depolarizing shift in the voltage dependence of activation reaching +30 mV upon co-expression of both mutant subunits. Potential interactions of T114 within the channel were analyzed by creating a 3D homology model of KV7.2 in an open state suggesting that this residue plays a central role in the formation of a stable interface between the S1-S2 and the S5 segment helices. This could be the explanation why substitution of the conserved threonine in KV7.2 and KV7.3 channels destabilizes the open and favors the closed state of these channels.

  8. Closing the feedback loop: engaging students in large first-year mathematics test revision sessions using pen-enabled screens

    NASA Astrophysics Data System (ADS)

    Donovan, Diane; Loch, Birgit

    2013-01-01

    How can active learning, peer learning and prompt feedback be achieved in large first-year mathematics classes? Further, what technologies may support these aims? In this article, we assert that test revision sessions in first-year mathematics held in a technology-enhanced lecture theatre can be highly interactive with students solving problems, learning from each other and receiving immediate feedback. This is facilitated by pen-enabled screens and synchronization software. We argue that the educational benefits achievable through the technology do outweigh the technological distractions, and that these benefits can be achieved by focused, targeted one-off sessions and not only by a semester-long, regular approach. Repeat mid-semester test revision sessions were offered on a non-compulsory basis using pen-enabled screens for all students. Students worked practice test questions and marked solutions to mathematical problems on the screens. Students' work was then displayed anonymously for their peers to see. Answers were discussed with the whole class. We discuss outcomes from two offerings of these sessions using student feedback and lecturer reflections and show the impact of participation on self-reported student confidence. Pedagogical approaches that the technology allowed for the first time in a large class are highlighted. Students responded uniformly positively.

  9. Identification of the Rps28 binding motif from yeast Edc3 involved in the autoregulatory feedback loop controlling RPS28B mRNA decay

    PubMed Central

    Kolesnikova, Olga; Back, Régis; Graille, Marc; Séraphin, Bertrand

    2013-01-01

    In the yeast Saccharomyces cerevisiae, the Edc3 protein was previously reported to participate in the auto-regulatory feedback loop controlling the level of the RPS28B messenger RNA (mRNA). We show here that Edc3 binds directly and tightly to the globular core of Rps28 ribosomal protein. This binding occurs through a motif that is present exclusively in Edc3 proteins from yeast belonging to the Saccharomycetaceae phylum. Functional analyses indicate that the ability of Edc3 to interact with Rps28 is not required for its general function and for its role in the regulation of the YRA1 pre-mRNA decay. In contrast, this interaction appears to be exclusively required for the auto-regulatory mechanism controlling the RPS28B mRNA decay. These observations suggest a plausible model for the evolutionary appearance of a Rps28 binding motif in Edc3. PMID:23956223

  10. Generation of "gigantic" ultra-short microwave pulses based on passive mode-locking effect in electron oscillators with saturable absorber in the feedback loop

    NASA Astrophysics Data System (ADS)

    Ginzburg, N. S.; Denisov, G. G.; Vilkov, M. N.; Zotova, I. V.; Sergeev, A. S.

    2016-05-01

    A periodic train of powerful ultrashort microwave pulses can be generated in electron oscillators with a non-linear saturable absorber installed in the feedback loop. This method of pulse formation resembles the passive mode-locking widely used in laser physics. Nevertheless, there is a specific feature in the mechanism of pulse amplification when consecutive energy extraction from different fractions of a stationary electron beam takes place due to pulse slippage over the beam caused by the difference between the wave group velocity and the electron axial velocity. As a result, the peak power of generated "gigantic" pulses can exceed not only the level of steady-state generation but also, in the optimal case, the power of the driving electron beam.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. SCAFFOLDING PROTEIN GAB1 SUSTAINS EPIDERMAL GROWTH FACTOR-INDUCED MITOGENIC AND SURVIVAL SIGNALING BY MULTIPLE POSITIVE FEEDBACK LOOPS

    PubMed Central

    Kiyatkin, Anatoly; Aksamitiene, Edita; Markevich, Nick I.; Borisov, Nikolay M.; Hoek, Jan B.; Kholodenko, Boris N.

    2008-01-01

    Grb2-associated binder 1 (GAB1) is a scaffold protein involved in numerous interactions that propagate signaling by growth factor and cytokine receptors. Here we explore in silico and validate in vivo the role of GAB1 in the control of mitogenic (Ras/MAPK) and survival (PI3K/Akt) signaling stimulated by epidermal growth factor (EGF). We built a comprehensive mechanistic model that allows for reliable predictions of temporal patterns of cellular responses to EGF under diverse perturbations, including different EGF doses, GAB1 suppression, expression of mutant proteins and pharmacological inhibitors. We show that the temporal dynamics of GAB1 tyrosine phosphorylation is significantly controlled by positive GAB1-PI3K feedback and negative MAPK-GAB1 feedback. Our experimental and computational results demonstrate that the essential function of GAB1 is to enhance PI3K/Akt activation and extend the duration of Ras/MAPK signaling. By amplifying positive interactions between survival and mitogenic pathways, GAB1 plays the critical role in cell proliferation and tumorigenesis. PMID:16687399

  18. Matrix Metalloproteinase (MMP) Proteolysis of the Extracellular Loop of Voltage-gated Sodium Channels and Potential Alterations in Pain Signaling*

    PubMed Central

    Remacle, Albert G.; Kumar, Sonu; Motamedchaboki, Khatereh; Cieplak, Piotr; Hullugundi, Swathi; Dolkas, Jennifer; Shubayev, Veronica I.; Strongin, Alex Y.

    2015-01-01

    Congenital insensitivity to pain (CIP) or congenital analgesia is a rare monogenic hereditary condition. This disorder is characterized by the inability to perceive any form of pain. Nonsense mutations in Nav.1.7, the main pain signaling voltage-gated sodium channel, lead to its truncations and, consequently, to the inactivation of the channel functionality. However, a non-truncating homozygously inherited missense mutation in a Bedouin family with CIP (Nav1.7-R907Q) has also been reported. Based on our currently acquired in-depth knowledge of matrix metalloproteinase (MMP) cleavage preferences, we developed the specialized software that predicts the presence of the MMP cleavage sites in the peptide sequences. According to our in silico predictions, the peptide sequence of the exposed extracellular unstructured region linking the S5–S6 transmembrane segments in the DII domain of the human Nav1.7 sodium channel is highly sensitive to MMP-9 proteolysis. Intriguingly, the CIP R907Q mutation overlaps with the predicted MMP-9 cleavage site sequence. Using MMP-9 proteolysis of the wild-type, CIP, and control peptides followed by mass spectrometry of the digests, we demonstrated that the mutant sequence is severalfold more sensitive to MMP-9 proteolysis relative to the wild type. Because of the substantial level of sequence homology among sodium channels, our data also implicate MMP proteolysis in regulating the cell surface levels of the Nav1.7, Nav1.6, and Nav1.8 channels, but not Nav1.9. It is likely that the aberrantly accelerated MMP-9 proteolysis during neurogenesis is a biochemical rational for the functional inactivation in Nav1.7 and that the enhanced cleavage of the Nav1.7-R907Q mutant is a cause of CIP in the Bedouin family. PMID:26283785

  19. Matrix Metalloproteinase (MMP) Proteolysis of the Extracellular Loop of Voltage-gated Sodium Channels and Potential Alterations in Pain Signaling.

    PubMed

    Remacle, Albert G; Kumar, Sonu; Motamedchaboki, Khatereh; Cieplak, Piotr; Hullugundi, Swathi; Dolkas, Jennifer; Shubayev, Veronica I; Strongin, Alex Y

    2015-09-18

    Congenital insensitivity to pain (CIP) or congenital analgesia is a rare monogenic hereditary condition. This disorder is characterized by the inability to perceive any form of pain. Nonsense mutations in Nav.1.7, the main pain signaling voltage-gated sodium channel, lead to its truncations and, consequently, to the inactivation of the channel functionality. However, a non-truncating homozygously inherited missense mutation in a Bedouin family with CIP (Nav1.7-R907Q) has also been reported. Based on our currently acquired in-depth knowledge of matrix metalloproteinase (MMP) cleavage preferences, we developed the specialized software that predicts the presence of the MMP cleavage sites in the peptide sequences. According to our in silico predictions, the peptide sequence of the exposed extracellular unstructured region linking the S5-S6 transmembrane segments in the DII domain of the human Nav1.7 sodium channel is highly sensitive to MMP-9 proteolysis. Intriguingly, the CIP R907Q mutation overlaps with the predicted MMP-9 cleavage site sequence. Using MMP-9 proteolysis of the wild-type, CIP, and control peptides followed by mass spectrometry of the digests, we demonstrated that the mutant sequence is severalfold more sensitive to MMP-9 proteolysis relative to the wild type. Because of the substantial level of sequence homology among sodium channels, our data also implicate MMP proteolysis in regulating the cell surface levels of the Nav1.7, Nav1.6, and Nav1.8 channels, but not Nav1.9. It is likely that the aberrantly accelerated MMP-9 proteolysis during neurogenesis is a biochemical rational for the functional inactivation in Nav1.7 and that the enhanced cleavage of the Nav1.7-R907Q mutant is a cause of CIP in the Bedouin family. PMID:26283785

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

    PubMed

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

    2015-07-28

    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.

  1. Feedback control of chlorine inductively coupled plasma etch processing

    SciTech Connect

    Lin Chaung; Leou, K.-C.; Shiao, K.-M.

    2005-03-01

    Feedback control has been applied to poly-Si etch processing using a chlorine inductively coupled plasma. Since the positive ion flux and ion energy incident upon the wafer surface are the key factors that influence the etch rate, the ion current and the root mean square (rms) rf voltage on the wafer stage, which are measured using an impedance meter connected to the wafer stage, are adopted as the controlled variables to enhance etch rate. The actuators are two 13.56 MHz rf power generators, which adjust ion density and ion energy, respectively. The results of closed-loop control show that the advantages of feedback control can be achieved. For example, with feedback control, etch rate variation under the transient chamber wall condition is reduced roughly by a factor of 2 as compared to the open-loop case. In addition, the capability of the disturbance rejection was also investigated. For a gas pressure variation of 20%, the largest etch rate variation is about 2.4% with closed-loop control as compared with as large as about 6% variation using open-loop control. Also the effect of ion current and rms rf voltage on etch rate was studied using 2{sup 2} factorial design whose results were used to derive a model equation. The obtained formula was used to adjust the set point of ion current and rf voltage so that the desired etch rate was obtained.

  2. 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

  3. Signal Transducer and Activator of Transcription 3/MicroRNA-21 Feedback Loop Contributes to Atrial Fibrillation by Promoting Atrial Fibrosis in a Rat Sterile Pericarditis Model

    PubMed Central

    Huang, Zhengrong; Chen, Xiao-jun; Qian, Cheng; Dong, Qian; Ding, Dan; Wu, Qiong-feng; Li, Jing; Wang, Hong-fei; Li, Wei-hua; Xie, Qiang; Cheng, Xiang; Liao, Yu-hua

    2016-01-01

    Background— Postoperative atrial fibrillation is a frequent complication in cardiac surgery. The aberrant activation of signal transducer and activator of transcription 3 (STAT3) contributes to the pathogenesis of atrial fibrillation. MicroRNA-21 (miR-21) promotes atrial fibrosis. Recent studies support the existence of reciprocal regulation between STAT3 and miR-21. Here, we test the hypothesis that these 2 molecules might form a feedback loop that contributes to postoperative atrial fibrillation by promoting atrial fibrosis. Methods and Results— A sterile pericarditis model was created using atrial surfaces dusted with sterile talcum powder in rats. The inflammatory cytokines interleukin (IL)-1β, IL-6, transforming growth factor-β, and tumor necrosis factor-α, along with STAT3 and miR-21, were highly upregulated in sterile pericarditis rats. The inhibition of STAT3 by S3I-201 resulted in miR-21 downregulation, which ameliorated atrial fibrosis and decreased the expression of the fibrosis-related genes, α-smooth muscle actin, collagen-1, and collagen-3; reduced the inhomogeneity of atrial conduction; and attenuated atrial fibrillation vulnerability. Meanwhile, treatment with antagomir-21 decreased STAT3 phosphorylation, alleviated atrial remodeling, abrogated sterile pericarditis–induced inhomogeneous conduction, and prevented atrial fibrillation promotion. The culturing of cardiac fibroblasts with IL-6 resulted in progressively augmented STAT3 phosphorylation and miR-21 levels. S3I-201 blocked IL-6 induced the expression of miR-21 and fibrosis-related genes in addition to cardiac fibroblast proliferation. Transfected antagomir-21 decreased the IL-6–induced cardiac fibroblast activation and STAT3 phosphorylation. The overexpression of miR-21 in cardiac fibroblasts caused the upregulation of STAT3 phosphorylation, enhanced fibrosis-related genes, and increased cell numbers. Conclusions— Our results have uncovered a novel reciprocal loop between STAT3

  4. 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

  5. Feedback loops blockade potentiates apoptosis induction and antitumor activity of a novel AKT inhibitor DC120 in human liver cancer.

    PubMed

    Yang, F; Deng, R; Qian, X-J; Chang, S-H; Wu, X-Q; Qin, J; Feng, G-K; Ding, K; Zhu, X-F

    2014-01-01

    The serine/threonine kinase AKT is generally accepted as a promising anticancer therapeutic target. However, the relief of feedback inhibition and enhancement of other survival pathways often attenuate the anticancer effects of AKT inhibitors. These compensatory mechanisms are very complicated and remain poorly understood. In the present study, we found a novel 2-pyrimidyl-5-amidothiazole compound, DC120, as an ATP competitive AKT kinase inhibitor that suppressed proliferation and induced apoptosis in liver cancer cells both in vitro and in vivo. DC120 blocked the phosphorylation of downstream molecules in the AKT signal pathway in dose- and time-dependent manners both in vitro and in vivo. However, unexpectedly, DC120 activated mammalian target of rapamycin complex 1 (mTORC1) pathway that was suggested by increased phosphorylation of 70KD ribosomal protein S6 kinase (P70S6K) and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1). The activated mTORC1 signal was because of increase of intracellular Ca(2+) via Ca(2+)/calmodulin (CaM)/ signaling to human vacuolar protein sorting 34 (hVps34) upon AKT inhibition. Meanwhile, DC120 attenuated the inhibitory effect of AKT on CRAF by decreasing phosphorylation of CRAF at Ser259 and thus activated the mitogen-activated protein kinase (MAPK) pathway. The activation of the mTORC1 and MAPK pathways by DC120 was not mutually dependent, and the combination of DC120 with mTORC1 inhibitor and/or MEK inhibitor induced significant apoptosis and growth inhibition both in vitro and in vivo. Taken together, the combination of AKT, mTORC1 and/or MEK inhibitors would be a promising therapeutic strategy for liver cancer treatment. PMID:24625973

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

    PubMed Central

    Han, Minho; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil

    2016-01-01

    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

  7. 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.

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

    PubMed

    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.

  9. 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

  10. Positive feedback loops for factor V and factor VII activation supply sensitivity to local surface tissue factor density during blood coagulation.

    PubMed

    Balandina, A N; Shibeko, A M; Kireev, D A; Novikova, A A; Shmirev, I I; Panteleev, M A; Ataullakhanov, F I

    2011-10-19

    Blood coagulation is triggered not only by surface tissue factor (TF) density but also by surface TF distribution. We investigated recognition of surface TF distribution patterns during blood coagulation and identified the underlying molecular mechanisms. For these investigations, we employed 1), an in vitro reaction-diffusion experimental model of coagulation; and 2), numerical simulations using a mathematical model of coagulation in a three-dimensional space. When TF was uniformly immobilized over the activating surface, the clotting initiation time in normal plasma increased from 4 min to >120 min, with a decrease in TF density from 100 to 0.7 pmol/m(2). In contrast, surface-immobilized fibroblasts initiated clotting within 3-7 min, independently of fibroblast quantity and despite a change in average surface TF density from 0.5 to 130 pmol/m(2). Experiments using factor V-, VII-, and VIII-deficient plasma and computer simulations demonstrated that different responses to these two TF distributions are caused by two positive feedback loops in the blood coagulation network: activation of the TF-VII complex by factor Xa, and activation of factor V by thrombin. This finding suggests a new role for these reactions: to supply sensitivity to local TF density during blood coagulation.

  11. CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells.

    PubMed

    Sakuma, Tomomi; Nakamoto, Tetsuya; Hemmi, Hiroaki; Kitazawa, Sohei; Kitazawa, Riko; Notomi, Takuya; Hayata, Tadayoshi; Ezura, Yoichi; Amagasa, Teruo; Noda, Masaki

    2012-07-01

    Tumor metastasis to bone is a serious pathological situation that causes severe pain, and deterioration in locomoter function. However, the mechanisms underlying tumor metastasis is still incompletely understood. CIZ/NMP4 is a nucleocytoplasmic shuttling protein and its roles in tumor cells have not been known. We, therefore, hypothesized the role of CIZ/NMP4 in B16 melanoma cells that metastasize to bone. CIZ/NMP4 is expressed in B16 cells. The CIZ/NMP4 expression levels are correlated to the metastatic activity in divergent types of melanoma cells. Overexpression of CIZ/NMP4 increased B16 cell migration in Trans-well assay. Conversely, siRNA-based knockdown of CIZ/NMP4 suppressed migratory activity of these cells. As RANKL promotes metastasis of tumor cells in bone, we tested its effect on CIZ in melanoma cells. RANKL treatment enhanced CIZ/NMP4 expression. This increase of CIZ by RANKL promoted migration. Conversely, we identified CIZ/NMP4 binding site in the promoter of RANKL. Furthermore, luciferase assay indicated that CIZ/NMP4 overexpression enhanced RANKL promoter activities, revealing a positive feedback loop of CIZ/NMP4 and RANKL in melanoma. These observations indicate that CIZ/NMP4 is critical regulator of metastasis of melanoma cells. PMID:22307584

  12. 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.

  13. STAT3 inhibition suppresses proliferation of retinoblastoma through down-regulation of positive feedback loop of STAT3/miR-17-92 clusters

    PubMed Central

    Jo, Dong Hyun; Kim, Jin Hyoung; Cho, Chang Sik; Cho, Young-Lai; Jun, Hyoung Oh; Yu, Young Suk; Min, Jeong-Ki; Kim, Jeong Hun

    2014-01-01

    Retinoblastoma, the most common intraocular malignant tumor in children, is characterized by the loss of both functional alleles of RB1 gene, which however alone cannot maintain malignant characteristics of retinoblastoma cells. Nevertheless, the investigation of other molecular aberrations such as matrix metalloproteinases (MMPs) and miRNAs is still lacking. In this study, we demonstrate that STAT3 is activated in retinoblastoma cells, Ki67-positive areas of in vivo orthotopic tumors in BALB/c nude mice, and human retinoblastoma tissues of the advanced stage. Furthermore, target genes of STAT3 including BCL2, BCL2L1, BIRC5, and MMP9 are up-regulated in retinoblastoma cells compared to other retinal constituent cells. Interestingly, STAT3 inhibition by targeted siRNA suppresses the proliferation of retinoblastoma cells and the formation of in vivo orthotopic tumors. In line with these results, STAT3 siRNA effectively induces down-regulation of target genes of STAT3. In addition, miRNA microarray analysis and further real-time PCR experiments with STAT3 siRNA treatment show that STAT3 activation is related to the up-regulation of miR-17-92 clusters in retinoblastoma cells via positive feedback loop between them. In conclusion, we suggest that STAT3 inhibition could be a potential therapeutic approach in retinoblastoma through the suppression of tumor proliferation. PMID:25359779

  14. CXCL3 contributes to CD133+ CSCs maintenance and forms a positive feedback regulation loop with CD133 in HCC via Erk1/2 phosphorylation

    PubMed Central

    Zhang, Lin; Zhang, Lixing; Li, Hong; Ge, Chao; Zhao, Fangyu; Tian, Hua; Chen, Taoyang; Jiang, Guoping; Xie, Haiyang; Cui, Ying; Yao, Ming; Li, Jinjun

    2016-01-01

    Although the chemotactic cytokine CXCL3 is thought to play an important role in tumor initiation and invasion, little is known about its function in hepatocellular carcinoma (HCC). In our previous study, we found that Ikaros inhibited CD133 expression via the MAPK pathway in HCC. Here, we showed that Ikaros may indirectly down-regulate CXCL3 expression in HCC cells, which leads to better outcomes in patients with CD133+ cancer stem cell (CSC) populations. CD133 overexpression induced CXCL3 expression, and silencing of CD133 down-regulated CXCL3 in HCC cells. Knockdown of CXCL3 inhibited CD133+ HCC CSCs’ self-renewal and tumorigenesis. The serum CXCL3 level was higher in HCC patients’ samples than that in healthy individual. HCC patients with higher CXCL3 expression displayed a poor prognosis, and a high level of CXCL3 was significantly associated with vascular invasion and tumor capsule formation. Exogenous CXCL3 induced Erk1/2 and ETS1 phosphorylation and promoted CD133 expression, indicating a positive feedback loop between CXCL3 and CD133 gene expression in HCC cells via Erk1/2 activation. Together, our findings indicated that CXCL3 might be a potent therapeutic target for HCC. PMID:27255419

  15. The Fra-1–miR-134–SDS22 feedback loop amplifies ERK/JNK signaling and reduces chemosensitivity in ovarian cancer cells

    PubMed Central

    Wu, Jianmin; Sun, Yimin; Zhang, Pei-Ying; Qian, Mengyao; Zhang, Hengchao; Chen, Xiao; Ma, Di; Xu, Yunsheng; Chen, Xiaoming; Tang, Kai-Fu

    2016-01-01

    The Fra-1 transcription factor is frequently upregulated in multiple types of tumors. Here we found that Fra-1 promotes miR-134 expression. miR-134 activates JNK and ERK by targeting SDS22, which in turn induces Fra-1 expression and leads to miR-134 upregulation. In addition, miR-134 augmented H2AX S139 phosphorylation by activating JNK and promoted non-homologous end joining (NHEJ)-mediated DNA repair. Therefore, ectopic miR-134 expression reduced chemosensitivity in ovarian cancer cells. Furthermore, miR-134 promotes cell proliferation, migration and invasion of ovarian cancer cells, and enhances tumor growth in vivo. Of particular significance, both Fra-1 and miR-134 are upregulated in ovarian cancer tissues, and Fra-1 and miR-134 expression is positively correlated. High levels of miR-134 expression were associated with a reduced median survival of ovarian cancer patients. Our study revealed that a Fra-1-miR-134 axis drives a positive feedback loop that amplifies ERK/JNK signaling and reduces chemosensitivity in ovarian cancer cells. PMID:27685628

  16. 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

    2016-03-01

    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.

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

    PubMed

    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.

  18. The neuronal microRNA miR-326 acts in a feedback loop with notch and has therapeutic potential against brain tumors.

    PubMed

    Kefas, Benjamin; Comeau, Laurey; Floyd, Desiree H; Seleverstov, Oleksandr; Godlewski, Jakub; Schmittgen, Tom; Jiang, Jinmai; diPierro, Charles G; Li, Yunqing; Chiocca, E Antonio; Lee, Jeongwu; Fine, Howard; Abounader, Roger; Lawler, Sean; Purow, Benjamin

    2009-12-01

    Little is known of microRNA interactions with cellular pathways. Few reports have associated microRNAs with the Notch pathway, which plays key roles in nervous system development and in brain tumors. We previously implicated the Notch pathway in gliomas, the most common and aggressive brain tumors. While investigating Notch mediators, we noted microRNA-326 was upregulated following Notch-1 knockdown. This neuronally expressed microRNA was not only suppressed by Notch but also inhibited Notch proteins and activity, indicating a feedback loop. MicroRNA-326 was downregulated in gliomas via decreased expression of its host gene. Transfection of microRNA-326 into both established and stem cell-like glioma lines was cytotoxic, and rescue was obtained with Notch restoration. Furthermore, miR-326 transfection reduced glioma cell tumorigenicity in vivo. Additionally, we found microRNA-326 partially mediated the toxic effects of Notch knockdown. This work demonstrates a microRNA-326/Notch axis, shedding light on the biology of Notch and suggesting microRNA-326 delivery as a therapy.

  19. 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

  20. A novel hypoxia-induced miR-147a regulates cell proliferation through a positive feedback loop of stabilizing HIF-1α

    PubMed Central

    Wang, Fan; Zhang, Haoxiang; Xu, Naihan; Huang, Nunu; Tian, Caiming; Ye, Anlin; Hu, Guangnan; He, Jie; Zhang, Yaou

    2016-01-01

    ABSTRACT Hypoxia is a general event in solid tumor growth. Therefore, induced cellular responses by hypoxia are important for tumorigenesis and tumor growth. MicroRNAs (miRNAs) have recently emerged as important regulators of hypoxia induced cellular responses. Here we report that miR-147a is a novel and crucial hypoxia induced miRNA. HIF-1α up-regulates the expression of miR-147a, and miR-147a in turn stabilizes and accumulates HIF-1α protein via directly targeting HIF-3α, a dominant negative regulator of HIF-1α. Subsequent studies in xenograft mouse model reveal that miR-147a is capable of inhibiting tumor growth. Collectively, these data demonstrate a positive feedback loop between HIF-1α, miR-147a and HIF-3α, which provide a new insight into the mechanism of miR-147a induced cell proliferation arrest under hypoxia. PMID:27260617

  1. Identification of a negative feedback loop between cyclic di-GMP-induced levels of IFI16 and p202 cytosolic DNA sensors and STING.

    PubMed

    Panchanathan, Ravichandran; Liu, Hongzhu; Xin, Duan; Choubey, Divaker

    2014-10-01

    A host type I IFN response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP (c-di-GMP) by STING (stimulator of IFN genes). Because the STING, an adaptor protein, links the cytosolic detection of DNA by the cytosolic DNA sensors such as the IFN-inducible human IFI16 and murine p202 proteins to the TBK1/IRF3 axis, we investigated whether c-di-GMP-induced signaling could regulate expression of IFI16 and p202 proteins. Here, we report that activation of c-di-GMP-induced signaling in human and murine cells increased steady-state levels of IFI16 and p202 proteins. The increase was c-di-GMP concentration- and time-dependent. Unexpectedly, treatment of cells with type I IFN decreased levels of the adaptor protein STING. Therefore, we investigated whether the IFI16 or p202 protein could regulate the expression of STING and activation of the TBK1/IRF3 axis. We found that constitutive knockdown of IFI16 or p202 expression in cells increased steady-state levels of STING. Additionally, the knockdown of IFI16 resulted in activation of the TBK1/IRF3 axis. Accordingly, increased levels of the IFI16 or p202 protein in cells decreased STING levels. Together, our observations identify a novel negative feedback loop between c-di-GMP-induced levels of IFI16 and p202 cytosolic DNA sensors and the adaptor protein STING.

  2. ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and c-Myc to reduce breast cancer proliferation

    PubMed Central

    Yuan, Yi; Anbalagan, Durkeshwari; Lee, Lay Hoon; Samy, Ramar Perumal; Shanmugam, Muthu K.; Kumar, Alan Prem; Sethi, Gautam; Lobie, Peter E.; Lim, Lina H.K.

    2016-01-01

    MiRNAs are endogenous ~22 nt RNAs which play critical regulatory roles in a wide range of biological and pathological processes, which can act as oncogenes or tumor suppressor genes depending on their target genes. We have recently shown that ANXA1 inhibits the expression of miRNAs including miR196a. Here, we show that miR196a was highly expressed in ER+ MCF-7 breast cancer cells when compared to normal mammary gland cells, with expression levels negatively correlating to ANXA1. ANXA1 inhibits the biogenesis of oncogenic miR-196a by suppressing primary-miR196a indirectly through the stimulation of c-myc and NFkB expression and activity in breast cancer cells. In a negative feedback loop, miR-196a directly inhibits ANXA1 and enhances breast cancer cell proliferation in vitro. Finally, miR196a promotes breast tumor growth in vivo. This study reports a novel regulatory circuit between ANXA1, NF-kB, c-myc and miR-196a which regulates breast cancer cell proliferation and tumor growth. PMID:27105503

  3. The inhibitory effects of AR/miR-190a/YB-1 negative feedback loop on prostate cancer and underlying mechanism.

    PubMed

    Xu, Shaohua; Wang, Tao; Song, Wen; Jiang, Tao; Zhang, Feng; Yin, Yu; Jiang, Shi-Wen; Wu, Kongming; Yu, Zuoren; Wang, Chenguang; Chen, Ke

    2015-08-28

    Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. MiR-190a belongs to the small noncoding RNA family and has an important role in breast cancer metastasis. However, it is still unknown whether miR-190a plays a role in prostate cancer development. Herein, we first observed AR/miR-190a/YB-1 forms an auto-regulatory negative feedback loop in prostate cancer: miR-190a expression was down-regulated by AR activation; YB-1 functions are as an AR activator; miR-190a inhibited AR expression and transactivation through direct binding to 3'UTR of YB-1 gene. MiR-190a contributes the human prostate cancer cell growth through AR-dependent signaling. Moreover, we examined the expression of miR-190a and observed a significant decrease in human prostate cancers. Reduced expression of miR-190a was inversely correlated to AR levels of prostate cancer patients, and patients with higher miR-190a expression in their tumor have improved tumor-free survival. Taken together, our findings identified a biochemical and functional link between miR-190a with reduced expression in advanced prostate cancer, YB-1 and AR signaling in prostate cancer.

  4. Protein-protein interactions generate hidden feedback and feed-forward loops to trigger bistable switches, oscillations and biphasic dose-responses.

    PubMed

    Varusai, Thawfeek M; Kolch, Walter; Kholodenko, Boris N; Nguyen, Lan K

    2015-10-01

    Protein-protein interactions (PPIs) defined as reversible association of two proteins to form a complex, are undoubtedly among the most common interaction motifs featured in cells. Recent large-scale proteomic studies have revealed an enormously complex interactome of the cell, consisting of tens of thousands of PPIs with numerous signalling hubs. PPIs have functional roles in regulating a wide range of cellular processes including signal transduction and post-translational modifications, and de-regulation of PPIs is implicated in many diseases including cancers and neuro-degenerative disorders. Despite the ubiquitous appearance and physiological significance of PPIs, our understanding of the dynamic and functional consequences of these simple motifs remains incomplete, particularly when PPIs occur within large biochemical networks. We employ quantitative, dynamic modelling to computationally analyse salient dynamic features of the PPI motifs and PPI-containing signalling networks varying in topological architecture. Our analyses surprisingly reveal that simple reversible PPI motifs, when being embedded into signalling cascades, could give rise to extremely rich and complex regulatory dynamics in the absence of explicit positive and negative feedback loops. Our work represents a systematic investigation of the dynamic properties of PPIs in signalling networks, and the results shed light on how this simple event may potentiate diverse and intricate behaviours in vivo. PMID:26266875

  5. 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

  6. False-lock performance improvement in Costas loops

    NASA Astrophysics Data System (ADS)

    Makarios, A. H.; Tozer, T. C.

    1982-10-01

    A technique is described to reduce the probability of false-lock in Costas loops. This is where a frequency offset arises at a multiple of half the incoming data rate due to finite bandwidth of the arm filters. A modification is described to process components of this offset so as to augment the feedback control voltage. The performance is analyzed and it is shown how certain false-lock positions may be avoided.

  7. Voltage-controlled narrowband and wide, variable-range four-segment quartz crystal oscillator.

    PubMed

    Ruslan, Ruzaini; Satoh, Tomio; Akitsu, Tetsuya

    2012-03-01

    In this work, our goal is to develop a voltage-controlled variable-frequency quartz crystal oscillator with narrowband response, wide, variable frequency range and the capacity to oscillate across the series resonance frequency using a four-segment configuration of a quartz crystal oscillator. In conventional quartz oscillators, the quartz resonator is inserted in the feedback loop between the input and the output of the active circuit, providing sufficient gain and the phase relation. In the oscillator developed here, the quartz crystal resonator is inserted between the loop circuit and the ground potential. The performance of the voltage-controlled variable-frequency oscillator is demonstrated across the series resonance frequency.

  8. miR-221 Promotes Epithelial-Mesenchymal Transition through Targeting PTEN and Forms a Positive Feedback Loop with β-catenin/c-Jun Signaling Pathway in Extra-Hepatic Cholangiocarcinoma

    PubMed Central

    Yao, Lei; Li, Guodong; Ma, Donglai; Sun, Chen; Gao, Shuang; Zhang, Ping

    2015-01-01

    Extrahepatic cholangiocarcinoma (EHCC) is a refractory malignancy with poor prognosis due to its early invasion, metastasis and recurrence after operation. Therefore, understanding the mechanisms of invasion and metastasis is the key to the development of new and effective therapeutic strategies for EHCC. In the present study we demonstrated that miR-221 promoted EHCC invasion and metastasis through targeting PTEN and formed a positive feedback loop with β-catenin/c-Jun signaling pathway. We found miR-221 was upregulated in EHCC specimens and CC cell lines. Moreover, miR-221 was found strongly associated with the metastasis and prognosis of EHCC patients. The expression of PTEN was downregulated in EHCC patients and CC cell lines, and was further demonstrated as one of the downstream targets of miR-221. In addition, our data indicated that β-catenin activated miR-221 through c-jun, while miR-221 enhanced β-catenin signaling induced-epithelial-mesenchymal transition (EMT) by targeting PTEN, hence forming a positive feedback loop in EHCC cell lines. In conclusion, our results suggested that miR-221 promotes EMT through targeting PTEN and forms a positive feedback loop with β-catenin/c-Jun signaling pathway in EHCC. PMID:26501139

  9. Loss of the oncogenic phosphatase PRL-3 promotes a TNF-R1 feedback loop that mediates triple-negative breast cancer growth.

    PubMed

    Gari, H H; DeGala, G D; Lucia, M S; Lambert, J R

    2016-01-01

    Stimulating tumor cell senescence and apoptosis are proven methods for therapeutically combating cancer. However, senescence and apoptosis are conventionally viewed as parallel, not sequential, processes. We have discovered that the metastasis-promoting phosphatase, PRL-3, is transcriptionally regulated by the NF-ĸB pathway in triple-negative breast cancer (TNBC) cells, and that PRL-3 knockdown elicits an autocrine tumor necrosis factor receptor 1 (TNF-R1) feedback loop that results in TNBC cell senescence followed by apoptosis. Knockdown of PRL-3 leads to rapid G1 cell cycle arrest and induction of a strong TNFα cytokine response that promotes a period of cellular senescence through TNF-R1-mediated activation of NF-ĸB. Senescent PRL-3 knockdown cells subsequently underwent apoptosis as a result of increased TNF-R1 signaling through the TNFα-associated extrinsic death pathway, shunting signaling away from the NF-ĸB cascade. These data suggest that TNF-R1 signaling dynamically re-programs after PRL-3 knockdown, from sustaining cell senescence through NF-ĸB to promoting apoptosis through TNF-R1 internalization and caspase-8 activation. The molecular mechanisms that determine the survival-death balance of TNF-R1 signaling are poorly understood, despite the fact that TNF-R1 has been extensively studied. Our results describe PRL-3 knockdown as a novel survival-death balance modifier of the TNF-R1 pathway, and show that senescent TNBC tumor cells can be sensitized to undergo apoptosis in a sequential manner. PMID:27526109

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. Shrimp with knockdown of LvSOCS2, a negative feedback loop regulator of JAK/STAT pathway in Litopenaeus vannamei, exhibit enhanced resistance against WSSV.

    PubMed

    Wang, Sheng; Song, Xuan; Zhang, Zijian; Li, Haoyang; L, Kai; Yin, Bin; He, Jianguo; Li, Chaozheng

    2016-12-01

    JAK/STAT pathway is one of cytokine signaling pathways and mediates diversity immune responses to protect host from viral infection. In this study, LvSOCS2, a member of suppressor of cytokine signaling (SOCS) families, has been cloned and identified from Litopenaeus vannamei. The full length of LvSOCS2 is 1601 bp, including an 1194 bp open reading frame (ORF) coding for a putative protein of 397 amino acids with a calculated molecular weight of ∼42.3 kDa. LvSOCS2 expression was most abundant in gills and could respond to the challenge of LPS, Vibrio parahaemolyticus, Staphhylococcus aureus, Poly (I: C) and white spot syndrome virus (WSSV). There are several STAT binding motifs presented in the proximal promoter region of LvSOCS2 and its expression was induced by LvJAK or LvSTAT protein in a dose dependent manner, suggesting LvSOCS2 could be the transcriptional target gene of JAK/STAT pathway. Moreover, the transcription of DmVir-1, a read out of the activation of JAK/STAT pathway in Drosophila, was promoted by LvJAK but inhibited by LvSOCS2, indicating that LvSOCS2 could be a negative regulator in this pathway and thus can form a negative feedback loop. Our previous study indicated that shrimp JAK/STAT pathway played a positive role against WSSV. In this study, RNAi-mediated knockdown of LvSOCS2 shrimps showed lower susceptibility to WSSV infection and caused lessened virus loads, which further demonstrated that the JAK/STAT pathway could function as an anti-viral immunity in shrimp. PMID:27497874

  16. Loss of the oncogenic phosphatase PRL-3 promotes a TNF-R1 feedback loop that mediates triple-negative breast cancer growth

    PubMed Central

    Gari, H H; DeGala, G D; Lucia, M S; Lambert, J R

    2016-01-01

    Stimulating tumor cell senescence and apoptosis are proven methods for therapeutically combating cancer. However, senescence and apoptosis are conventionally viewed as parallel, not sequential, processes. We have discovered that the metastasis-promoting phosphatase, PRL-3, is transcriptionally regulated by the NF-ĸB pathway in triple-negative breast cancer (TNBC) cells, and that PRL-3 knockdown elicits an autocrine tumor necrosis factor receptor 1 (TNF-R1) feedback loop that results in TNBC cell senescence followed by apoptosis. Knockdown of PRL-3 leads to rapid G1 cell cycle arrest and induction of a strong TNFα cytokine response that promotes a period of cellular senescence through TNF-R1-mediated activation of NF-ĸB. Senescent PRL-3 knockdown cells subsequently underwent apoptosis as a result of increased TNF-R1 signaling through the TNFα-associated extrinsic death pathway, shunting signaling away from the NF-ĸB cascade. These data suggest that TNF-R1 signaling dynamically re-programs after PRL-3 knockdown, from sustaining cell senescence through NF-ĸB to promoting apoptosis through TNF-R1 internalization and caspase-8 activation. The molecular mechanisms that determine the survival–death balance of TNF-R1 signaling are poorly understood, despite the fact that TNF-R1 has been extensively studied. Our results describe PRL-3 knockdown as a novel survival–death balance modifier of the TNF-R1 pathway, and show that senescent TNBC tumor cells can be sensitized to undergo apoptosis in a sequential manner. PMID:27526109

  17. 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

  18. Shrimp with knockdown of LvSOCS2, a negative feedback loop regulator of JAK/STAT pathway in Litopenaeus vannamei, exhibit enhanced resistance against WSSV.

    PubMed

    Wang, Sheng; Song, Xuan; Zhang, Zijian; Li, Haoyang; L, Kai; Yin, Bin; He, Jianguo; Li, Chaozheng

    2016-12-01

    JAK/STAT pathway is one of cytokine signaling pathways and mediates diversity immune responses to protect host from viral infection. In this study, LvSOCS2, a member of suppressor of cytokine signaling (SOCS) families, has been cloned and identified from Litopenaeus vannamei. The full length of LvSOCS2 is 1601 bp, including an 1194 bp open reading frame (ORF) coding for a putative protein of 397 amino acids with a calculated molecular weight of ∼42.3 kDa. LvSOCS2 expression was most abundant in gills and could respond to the challenge of LPS, Vibrio parahaemolyticus, Staphhylococcus aureus, Poly (I: C) and white spot syndrome virus (WSSV). There are several STAT binding motifs presented in the proximal promoter region of LvSOCS2 and its expression was induced by LvJAK or LvSTAT protein in a dose dependent manner, suggesting LvSOCS2 could be the transcriptional target gene of JAK/STAT pathway. Moreover, the transcription of DmVir-1, a read out of the activation of JAK/STAT pathway in Drosophila, was promoted by LvJAK but inhibited by LvSOCS2, indicating that LvSOCS2 could be a negative regulator in this pathway and thus can form a negative feedback loop. Our previous study indicated that shrimp JAK/STAT pathway played a positive role against WSSV. In this study, RNAi-mediated knockdown of LvSOCS2 shrimps showed lower susceptibility to WSSV infection and caused lessened virus loads, which further demonstrated that the JAK/STAT pathway could function as an anti-viral immunity in shrimp.

  19. The CaVβ Subunit Protects the I-II Loop of the Voltage-gated Calcium Channel CaV2.2 from Proteasomal Degradation but Not Oligoubiquitination.

    PubMed

    Page, Karen M; Rothwell, Simon W; Dolphin, Annette C

    2016-09-23

    CaVβ subunits interact with the voltage-gated calcium channel CaV2.2 on a site in the intracellular loop between domains I and II (the I-II loop). This interaction influences the biophysical properties of the channel and leads to an increase in its trafficking to the plasma membrane. We have shown previously that a mutant CaV2.2 channel that is unable to bind CaVβ subunits (CaV2.2 W391A) was rapidly degraded (Waithe, D., Ferron, L., Page, K. M., Chaggar, K., and Dolphin, A. C. (2011) J. Biol. Chem. 286, 9598-9611). Here we show that, in the absence of CaVβ subunits, a construct consisting of the I-II loop of CaV2.2 was directly ubiquitinated and degraded by the proteasome system. Ubiquitination could be prevented by mutation of all 12 lysine residues in the I-II loop to arginines. Including a palmitoylation motif at the N terminus of CaV2.2 I-II loop was insufficient to target it to the plasma membrane in the absence of CaVβ subunits even when proteasomal degradation was inhibited with MG132 or ubiquitination was prevented by the lysine-to-arginine mutations. In the presence of CaVβ subunit, the palmitoylated CaV2.2 I-II loop was protected from degradation, although oligoubiquitination could still occur, and was efficiently trafficked to the plasma membrane. We propose that targeting to the plasma membrane requires a conformational change in the I-II loop that is induced by binding of the CaVβ subunit. PMID:27489103

  20. The CaVβ Subunit Protects the I-II Loop of the Voltage-gated Calcium Channel CaV2.2 from Proteasomal Degradation but Not Oligoubiquitination*

    PubMed Central

    Page, Karen M.; Rothwell, Simon W.; Dolphin, Annette C.

    2016-01-01

    CaVβ subunits interact with the voltage-gated calcium channel CaV2.2 on a site in the intracellular loop between domains I and II (the I-II loop). This interaction influences the biophysical properties of the channel and leads to an increase in its trafficking to the plasma membrane. We have shown previously that a mutant CaV2.2 channel that is unable to bind CaVβ subunits (CaV2.2 W391A) was rapidly degraded (Waithe, D., Ferron, L., Page, K. M., Chaggar, K., and Dolphin, A. C. (2011) J. Biol. Chem. 286, 9598–9611). Here we show that, in the absence of CaVβ subunits, a construct consisting of the I-II loop of CaV2.2 was directly ubiquitinated and degraded by the proteasome system. Ubiquitination could be prevented by mutation of all 12 lysine residues in the I-II loop to arginines. Including a palmitoylation motif at the N terminus of CaV2.2 I-II loop was insufficient to target it to the plasma membrane in the absence of CaVβ subunits even when proteasomal degradation was inhibited with MG132 or ubiquitination was prevented by the lysine-to-arginine mutations. In the presence of CaVβ subunit, the palmitoylated CaV2.2 I-II loop was protected from degradation, although oligoubiquitination could still occur, and was efficiently trafficked to the plasma membrane. We propose that targeting to the plasma membrane requires a conformational change in the I-II loop that is induced by binding of the CaVβ subunit. PMID:27489103

  1. Subwavelength position sensing using nonlinear feedback and wave chaos.

    PubMed

    Cohen, Seth D; Cavalcante, Hugo L D de S; Gauthier, Daniel J

    2011-12-16

    We demonstrate a position-sensing technique that relies on the inherent sensitivity of chaos, where we illuminate a subwavelength object with a complex structured radio-frequency field generated using wave chaos and nonlinear feedback. We operate the system in a quasiperiodic state and analyze changes in the frequency content of the scalar voltage signal in the feedback loop. This allows us to extract the object's position with a one-dimensional resolution of ~λ/10,000 and a two-dimensional resolution of ~λ/300, where λ is the shortest wavelength of the illuminating source.

  2. MHD computation of feedback of resistive-shell instabilities in the reversed field pinch

    SciTech Connect

    Zita, E.J.; Prager, S.C.; 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.

  3. A hormone-dependent feedback-loop controls androgen receptor levels by limiting MID1, a novel translation enhancer and promoter of oncogenic signaling

    PubMed Central

    2014-01-01

    Background High androgen receptor (AR) level in primary tumour predicts increased prostate cancer (PCa)-specific mortality. Furthermore, activations of the AR, PI3K, mTOR, NFκB and Hedgehog (Hh) signaling pathways are involved in the fatal development of castration-resistant prostate cancer during androgen ablation therapy. MID1, a negative regulator of the tumor-suppressor PP2A, is known to promote PI3K, mTOR, NFκB and Hh signaling. Here we investigate the interaction of MID1 and AR. Methods AR and MID1 mRNA and protein levels were measured by qPCR, Western blot and immunohistochemistry. Co-immunoprecipitation followed by PCR and RNA-pull-down followed by Western blot was used to investigate protein-mRNA interaction, chromatin-immunoprecipitation followed by next-generation sequencing for identification of AR chromatin binding sites. AR transcriptional activity and activity of promoter binding sites for AR were analyzed by reporter gene assays. For knockdown or overexpression of proteins of interest prostate cancer cells were transfected with siRNA or expression plasmids, respectively. Results The microtubule-associated MID1 protein complex associates with AR mRNA via purine-rich trinucleotide repeats, expansions of which are known to correlate with ataxia and cancer. The level of MID1 directly correlates with the AR protein level in PCa cells. Overexpression of MID1 results in a several fold increase in AR protein and activity without major changes in mRNA-levels, whereas siRNA-triggered knockdown of MID1 mRNA reduces AR-protein levels significantly. Upregulation of AR protein by MID1 occurs via increased translation as no major changes in AR protein stability could be observed. AR on the other hand, regulates MID1 via several functional AR binding sites in the MID1 gene, and, in the presence of androgens, exerts a negative feedback loop on MID1 transcription. Thus, androgen withdrawal increases MID1 and concomitantly AR-protein levels. In line with this, MID1

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. Global Feedback Simulator

    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

  9. 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.

  10. NMR analysis of interaction of LqhalphaIT scorpion toxin with a peptide corresponding to the D4/S3-S4 loop of insect para voltage-gated sodium channel.

    PubMed

    Schnur, Einat; Turkov, Michael; Kahn, Roy; Gordon, Dalia; Gurevitz, Michael; Anglister, Jacob

    2008-01-22

    Voltage-gated sodium channels (Navs) are large transmembrane proteins that initiate action potential in electrically excitable cells. This central role in the nervous system has made them a primary target for a large number of neurotoxins. Scorpion alpha-neurotoxins bind to Navs with high affinity and slow their inactivation, causing a prolonged action potential. Despite the similarity in their mode of action and three-dimensional structure, alpha-toxins exhibit great variations in selectivity toward insect and mammalian Navs, suggesting differences in the binding surfaces of the toxins and the channels. The scorpion alpha-toxin binding site, termed neurotoxin receptor site 3, has been shown to involve the extracellular S3-S4 loop in domain 4 of the alpha-subunit of voltage-gated sodium channels (D4/S3-S4). In this study, the binding site for peptides corresponding to the D4/S3-S4 loop of the para insect Nav was mapped on the highly insecticidal alpha-neurotoxin, LqhalphaIT, from the scorpion Leiurus quinquestriatus hebraeus, by following changes in the toxin amide 1H and 15N chemical shifts upon binding. This analysis suggests that the five-residue turn (residues LqK8-LqC12) of LqhalphaIT and those residues in its vicinity interact with the D4/S3-S4 loop of Nav. Residues LqR18, LqW38, and LqA39 could also form a patch contributing to the interaction with D4/S3-S4. Moreover, a new bioactive residue, LqV13, was identified as being important for Nav binding and specifically for the interaction with the D4/S3-S4 loop. The contribution of LqV13 to NaV binding was further verified by mutagenesis. Future studies involving other extracellular regions of Navs are required for further characterization of the structure of the LqhalphaIT-Navs binding site.

  11. 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

  12. 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

    2016-04-27

    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

  13. 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

  14. 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

  15. miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1

    PubMed Central

    Amodio, N; Di Martino, M T; Foresta, U; Leone, E; Lionetti, M; Leotta, M; Gullà, A M; Pitari, M R; Conforti, F; Rossi, M; Agosti, V; Fulciniti, M; Misso, G; Morabito, F; Ferrarini, M; Neri, A; Caraglia, M; Munshi, N C; Anderson, K C; Tagliaferri, P; Tassone, P

    2012-01-01

    MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified Sp1, a transcription factor endowed with oncogenic activity, as a negative regulator of miR-29b expression in MM cells. Since Sp1 expression and functions are regulated via the 26S proteasome, we investigated the effects of bortezomib on miR-29b-Sp1 loop, showing that miR-29b levels were indeed upregulated by the drug. At the same time, the bortezomib/miR-29b combination produced significant pro-apoptotic effects. We also demonstrated that the PI3K/AKT pathway plays a major role in the regulation of miR-29b-Sp1 loop and induction of apoptosis in MM cells. Finally, MM xenografts constitutively expressing miR-29b showed significant reduction of their tumorigenic potential. Our findings indicate that miR-29b is involved in a regulatory loop amenable of pharmacologic intervention and modulates the anti-MM activity of bortezomib in MM cells. PMID:23190608

  16. miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1.

    PubMed

    Amodio, N; Di Martino, M T; Foresta, U; Leone, E; Lionetti, M; Leotta, M; Gullà, A M; Pitari, M R; Conforti, F; Rossi, M; Agosti, V; Fulciniti, M; Misso, G; Morabito, F; Ferrarini, M; Neri, A; Caraglia, M; Munshi, N C; Anderson, K C; Tagliaferri, P; Tassone, P

    2012-01-01

    MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified Sp1, a transcription factor endowed with oncogenic activity, as a negative regulator of miR-29b expression in MM cells. Since Sp1 expression and functions are regulated via the 26S proteasome, we investigated the effects of bortezomib on miR-29b-Sp1 loop, showing that miR-29b levels were indeed upregulated by the drug. At the same time, the bortezomib/miR-29b combination produced significant pro-apoptotic effects. We also demonstrated that the PI3K/AKT pathway plays a major role in the regulation of miR-29b-Sp1 loop and induction of apoptosis in MM cells. Finally, MM xenografts constitutively expressing miR-29b showed significant reduction of their tumorigenic potential. Our findings indicate that miR-29b is involved in a regulatory loop amenable of pharmacologic intervention and modulates the anti-MM activity of bortezomib in MM cells. PMID:23190608

  17. 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.

  18. 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.

  19. 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…

  20. 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…

  1. Model Predicts That MKP1 and TAB1 Regulate p38α Nuclear Pulse and Its Basal Activity through Positive and Negative Feedback Loops in Response to IL-1

    PubMed Central

    Singh, Raghvendra

    2016-01-01

    Interleukin-1 mediates inflammation and stress response through nuclear activity of p38α. Although IL-1 receptor is not degraded, p38α activation is transient. IL-1 also causes cell migration and EMT by modulating cell-cell junctions. Although molecules involved in p38 activation are known, mechanism of the transient nuclear response and its basal activity remains unknown. By mathematical modeling of IL1/p38 signaling network, we show that IL-1 induces robust p38α activation both in the nucleus and in the cytoplasm/membrane. While nuclear response consists of an acute phase, membrane response resembles a step change. Following stimulation, p38α activity returns to a basal level in absence of receptor degradation. While nuclear pulse is controlled by MKP1 through a negative feedback to pp38, its basal activity is controlled by both TAB1 and MKP1 through a positive feedback loop. Our model provides insight into the mechanism of p38α activation, reason for its transient nuclear response, and explanation of the basal activity of MKK3/6 and p38α, which has been experimentally observed by other groups. PMID:27314954

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Feedback: A Systems Approach to Evaluation and Course Design. Working Papers No. 21.

    ERIC Educational Resources Information Center

    Holmes, John

    Two types of feedback are examined, and their use in controlling the processes of instructional development and improvement are discussed. Closed-loop feedback, the most direct, uses immediate feedback about a process or product to make immediate adjustments in it. Open-loop feedback, in which input cannot be changed immediately, uses feedback to…

  7. 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.

  8. 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.

  9. A novel double-negative feedback loop between miR-489 and the HER2-SHP2-MAPK signaling axis regulates breast cancer cell proliferation and tumor growth

    PubMed Central

    Lee, Ji Shin; Markoutsa, Eleni; Jie, Chunfa; Liu, Shou; Botbyl, Rachel; Reisman, David; Xu, Peisheng; Chen, Hexin

    2016-01-01

    Human epidermal growth factor receptor 2 (HER2 or ErBb2) is a receptor tyrosine kinase overexpressed in 20-30% of breast cancers and associated with poor prognosis and outcome. Dysregulation of several microRNAs (miRNAs) plays a key role in breast cancer progression and metastasis. In this study, we screened and identified miRNAs dysregualted in HER2-positive breast cancer cells. Our molecular study demonstrated that miR-489 was specifically downregulated by the HER2-downstream signaling, especially through the MAPK pathway. Restoration or overexpression of miR-489 in HER2-positive breast cancer cells significantly inhibited cell growth in vitro and decreased the tumorigenecity and tumor growth in xenograft mice. Mechanistically, we found that overexpression of miR-489 led to the decreased levels of HER2 and SHP2 and thus attenuated HER2-downstream signaling. Furthermore, we for the first time demonstrated that HER2 is a direct target of miR-489 and therefore HER2-SHP2-MAPK and miR-489 signaling pathways form a mutually inhibitory loop. Using quantitative real-time PCR analysis and Fluorescent in situ hybridization technique (FISH), we found that miR-489 was expressed at significantly lower level in tumor tissues compared to the adjacent normal tissues. Downregulation of miR-489 in breast cancers was associated with aggressive tumor phenotypes. Overall, our results define a double-negative feedback loop involving miR-489 and the HER2-SHP2-MAPK signaling axis that can regulate breast cancer cell proliferation and tumor progression and might have therapeutic relevance for HER2-positive breast cancer. PMID:26918448

  10. 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…

  11. 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.

  12. P-REX1 creates a positive feedback loop to activate growth factor receptor, PI3K/AKT, and MEK/ERK signaling in breast cancer

    PubMed Central

    Dillon, Lloye M.; Bean, Jennifer R.; Yang, Wei; Shee, Kevin; Symonds, Lynn K.; Balko, Justin M.; McDonald, W. Hayes; Liu, Shuying; Gonzalez-Angulo, Ana M.; Mills, Gordon B.; Arteaga, Carlos L.; Miller, Todd W.

    2014-01-01

    Phosphatidylinositol 3-kinase (PI3K) promotes cancer cell survival, migration, growth, and proliferation by generating phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the inner leaflet of the plasma membrane. PIP3 recruits pleckstrin homology (PH) domain-containing proteins to the membrane to activate oncogenic signaling cascades. Anti-cancer therapeutics targeting the PI3K/AKT/mTOR pathway are in clinical development. In a mass spectrometric screen to identify PIP3-regulated proteins in breast cancer cells, levels of the Rac activator PIP3-dependent Rac exchange factor 1 (P-REX1) increased in response to PI3K inhibition, and decreased upon loss of the PI3K antagonist PTEN. P-REX1 mRNA and protein levels were positively correlated with ER expression, and inversely correlated with PI3K pathway activation in breast tumors as assessed by gene expression and phosphoproteomic analyses. P-REX1 increased activation of Rac1, PI3K/AKT, and MEK/ERK signaling in a PTEN-independent manner, and promoted cell and tumor viability. Loss of P-REX1 or inhibition of Rac suppressed PI3K/AKT and MEK/ERK, and decreased viability. P-REX1 also promoted insulin-like growth factor-1 receptor (IGF-1R) activation, suggesting that P-REX1 provides positive feedback to activators upstream of PI3K. In support of a model where PIP3-driven P-REX1 promotes both PI3K/AKT and MEK/ERK signaling, high levels of P-REX1 mRNA (but not phospho-AKT or a transcriptomic signature of PI3K activation) were predictive of sensitivity to PI3K inhibitors among breast cancer cell lines. P-REX1 expression was highest in ER+ breast tumors compared to many other cancer subtypes, suggesting that neutralizing the P-REX1/Rac axis may provide a novel therapeutic approach to selectively abrogate oncogenic signaling in breast cancer cells. PMID:25284585

  13. 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.

  14. miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR-p-PI3K/AKT-c-JUN.

    PubMed

    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

  15. STAT3 Induction of MiR-146b Forms a Feedback Loop to Inhibit the NF-κB to IL-6 Signaling Axis and STAT3-Driven Cancer Phenotypes

    PubMed Central

    Xiang, Michael; Birkbak, Nicolai J.; Vafaizadeh, Vida; Walker, Sarah R.; Yeh, Jennifer E.; Liu, Suhu; Kroll, Yasmin; Boldin, Mark; Taganov, Konstantin; Groner, Bernd; Richardson, Andrea L.; Frank, David A.

    2014-01-01

    Interleukin-6 (IL-6)-mediated activation of signal transducer and activator of transcription 3 (STAT3) is a mechanism by which chronic inflammation can contribute to cancer and is a common oncogenic event. We discovered a pathway the loss of which is associated with persistent STAT3 activation in human cancer. We found that the gene encoding the tumor suppressor microRNA miR-146b is a direct STAT3 target gene and its expression was increased in normal breast epithelial cells but decreased in tumor cells. Methylation of the miR-146b promoter, which inhibited STAT3-mediated induction of expression, was increased in primary breast cancers. Moreover, we found that miR-146b inhibited nuclear factor κB (NF-κB)-dependent production of IL-6, subsequent STAT3 activation, and IL-6/STAT3-driven migration and invasion in breast cancer cells, thereby establishing a negative feedback loop. In addition, higher expression of miR-146b was positively correlated with patient survival in breast cancer subtypes with increased IL6 expression and STAT3 phosphorylation. Our results identify an epigenetic mechanism of crosstalk between STAT3 and NF-κB relevant to constitutive STAT3 activation in malignancy and the role of inflammation in oncogenesis. PMID:24473196

  16. 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.

  17. Supervisor Feedback.

    ERIC Educational Resources Information Center

    Hayman, Marilyn J.

    1981-01-01

    Investigated the effectiveness of supervisor feedback in contributing to learning counseling skills. Counselor trainees (N=64) were assigned to supervisor feedback, no supervisor feedback, or control groups for three training sessions. Results indicated counseling skills were learned best by students with no supervisor feedback but self and peer…

  18. 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.

  19. 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.

  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.

  1. 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 varieties.

    PubMed

    Lin, Meng-yi; Chai, Kuo-hsing; Ko, Swee-suak; Kuang, Lin-yun; Lur, Huu-sheng; Charng, Yee-yung

    2014-04-01

    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.

  2. Modular high voltage power supply for chemical analysis

    SciTech Connect

    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.

  3. 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.

  4. Modular high voltage power supply for chemical analysis

    SciTech Connect

    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.

  5. 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)

  6. 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)

  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. 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.

  9. 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.

  10. Electronically Tunable Differential Integrator: Linear Voltage Controlled Quadrature Oscillator.

    PubMed

    Nandi, Rabindranath; Pattanayak, Sandhya; Venkateswaran, Palaniandavar; Das, Sagarika

    2015-01-01

    A new electronically tunable differential integrator (ETDI) and its extension to voltage controlled quadrature oscillator (VCQO) design with linear tuning law are proposed; the active building block is a composite current feedback amplifier with recent multiplication mode current conveyor (MMCC) element. Recently utilization of two different kinds of active devices to form a composite building block is being considered since it yields a superior functional element suitable for improved quality circuit design. The integrator time constant (τ) and the oscillation frequency (ω o ) are tunable by the control voltage (V) of the MMCC block. Analysis indicates negligible phase error (θ e ) for the integrator and low active ω o -sensitivity relative to the device parasitic capacitances. Satisfactory experimental verifications on electronic tunability of some wave shaping applications by the integrator and a double-integrator feedback loop (DIFL) based sinusoid oscillator with linear f o variation range of 60 KHz~1.8 MHz at low THD of 2.1% are verified by both simulation and hardware tests. PMID:27347537

  11. 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

  12. 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) 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

  13. 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) 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.

  14. 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.

  15. 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.

  16. 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.)

  17. Closed-Loop Neuroscience and Non-Invasive Brain Stimulation: A Tale of Two Loops.

    PubMed

    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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Electrometer preamplifier has drift correction feedback

    NASA Technical Reports Server (NTRS)

    Labarthe, L. C.

    1965-01-01

    Negative feedback circuit corrects output drift in an electrometer. The negative feedback is used in the no signal state to maintain the output level at zero reference. Drift voltage storage in the signal on state is also used to provide a drift-free readout.

  6. Explore the Effects of Microstructural Defects on Voltage Fade of Li- and Mn-Rich Cathodes

    DOE PAGES

    Hu, E.; Lyu, Y.; Xin, H.; Xin, H. L.; Liu, J.; Han, L.; Bak, S. -M.; Bai, J.; Yu, X.; Li, H.; et al

    2016-09-26

    Li- and Mn-rich (LMR) cathode materials have been considered as promising candidates for energy storage applications due to high energy density. However, these materials suffer from a serious problem of voltage fade. Oxygen loss and the layer to spinel phase transition are two major contributors of such voltage fade. In this paper, using a combination of x-ray diffraction (XRD), pair distribution function (PDF), x-ray absorption (XAS) techniques and aberration-corrected scanning transmission electron microscopy (STEM), we studied the effects of micro structural defects, especially the grain boundaries on the oxygen loss and layered-to-spinel phase transition through prelithiation of a model compoundmore » Li2Ru0.5Mn0.5O3. It is found that the nano-sized micro structural defects, especially the large amount of grain boundaries created by the prelithiation can greatly accelerate the oxygen loss and voltage fade. Defects (such as nano-sized grain boundaries) and oxygen release form a positive feedback loop, promote each other during cycling, and accelerate the two major voltage fade contributors: the transition metal reduction and layered-to-spinel phase transition. These results clearly demonstrate the important relationships among the oxygen loss, microstructural defects and voltage fade. The importance of maintaining good crystallinity and protecting the surface of LMR material are also suggested.« less

  7. 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.

  8. Comparison of the domain and frequency domain state feedbacks

    SciTech Connect

    Zhang, S.Y.

    1986-01-01

    In this paper, we present explicitly the equivalence of the time domain and frequency domain state feedbacks, as well as the dynamic state feedback and a modified frequency domain state feedback, from the closed-loop transfer function point of view. The difference of the two approaches is also shown.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Development of a low noise induction magnetic sensor using magnetic flux negative feedback in the time domain.

    PubMed

    Wang, X G; Shang, X L; Lin, J

    2016-05-01

    Time-domain electromagnetic system can implement great depth detection. As for the electromagnetic system, the receiver utilized an air coil sensor, and the matching mode of the sensor employed the resistance matching method. By using the resistance matching method, the vibration of the coil in the time domain can be effectively controlled. However, the noise of the sensor, especially the noise at the resonance frequency, will be increased as well. In this paper, a novel design of a low noise induction coil sensor is proposed, and the experimental data and noise characteristics are provided. The sensor is designed based on the principle that the amplified voltage will be converted to current under the influence of the feedback resistance of the coil. The feedback loop around the induction coil exerts a magnetic field and sends the negative feedback signal to the sensor. The paper analyses the influence of the closed magnetic feedback loop on both the bandwidth and the noise of the sensor. The signal-to-noise ratio is improved dramatically.

  18. Development of a low noise induction magnetic sensor using magnetic flux negative feedback in the time domain.

    PubMed

    Wang, X G; Shang, X L; Lin, J

    2016-05-01

    Time-domain electromagnetic system can implement great depth detection. As for the electromagnetic system, the receiver utilized an air coil sensor, and the matching mode of the sensor employed the resistance matching method. By using the resistance matching method, the vibration of the coil in the time domain can be effectively controlled. However, the noise of the sensor, especially the noise at the resonance frequency, will be increased as well. In this paper, a novel design of a low noise induction coil sensor is proposed, and the experimental data and noise characteristics are provided. The sensor is designed based on the principle that the amplified voltage will be converted to current under the influence of the feedback resistance of the coil. The feedback loop around the induction coil exerts a magnetic field and sends the negative feedback signal to the sensor. The paper analyses the influence of the closed magnetic feedback loop on both the bandwidth and the noise of the sensor. The signal-to-noise ratio is improved dramatically. PMID:27250444

  19. Analysis of sampling and quantization effects on the performance of PN code tracking loops

    NASA Technical Reports Server (NTRS)

    Quirk, K. J.; Srinivasan, M.

    2002-01-01

    Pseudonoise (PN) code tracking loops in direct-sequence spread-spectrum systems are often implemented using digital hardware. Performance degradation due to quantization and sampling effects is not adequately characterized by the traditional analog system feedback loop analysis.

  20. Closed-loop approach to thermodynamics

    NASA Astrophysics Data System (ADS)

    Goupil, C.; Ouerdane, H.; Herbert, E.; Benenti, G.; D'Angelo, Y.; Lecoeur, Ph.

    2016-09-01

    We present the closed-loop approach to linear nonequilibrium thermodynamics considering a generic heat engine dissipatively connected to two temperature baths. The system is usually quite generally characterized by two parameters: the output power P and the conversion efficiency η , to which we add a third one, the working frequency ω . We establish that a detailed understanding of the effects of the dissipative coupling on the energy conversion process requires only knowing two quantities: the system's feedback factor β and its open-loop gain A0, which product A0β characterizes the interplay between the efficiency, the output power, and the operating rate of the system. By raising the abstract hermodynamic analysis to a higher level, the feedback loop approach provides a versatile and economical, hence fairly efficient, tool for the study of any conversion engine operation for which a feedback factor can be defined.

  1. Coress feedback

    PubMed Central

    2012-01-01

    This issue of CORESS feedback highlights yet again the importance of checking medications before administration and of adequate handover. Documentation of important medical data including drug allergies, as failed to happen in the case described below, is vital. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Constant voltage electro-slag remelting control

    DOEpatents

    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.

  6. Symbolic Dynamics of Biological Feedback Networks

    NASA Astrophysics Data System (ADS)

    Pigolotti, Simone; Krishna, Sandeep; Jensen, Mogens H.

    2009-02-01

    We formulate general rules for a coarse graining of the dynamics, which we term “symbolic dynamics,” of feedback networks with monotonic interactions, such as most biological modules. Networks which are more complex than simple cyclic structures can exhibit multiple different symbolic dynamics. Nevertheless, we show several examples where the symbolic dynamics is dominated by a single pattern that is very robust to changes in parameters and is consistent with the dynamics being dictated by a single feedback loop. Our analysis provides a method for extracting these dominant loops from short time series, even if they only show transient trajectories.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Feedback control of HfO{sub 2} etch processing in inductively coupled Cl{sub 2}/N{sub 2}/Ar plasmas

    SciTech Connect

    Lin Chaung; Leou, K.-C.; Li, T.-C.; Lee, L.-S.; Tzeng, P.-J.

    2008-09-15

    The etch rate of HfO{sub 2} etch processing has been feedback controlled in inductively coupled Cl{sub 2}/N{sub 2}/Ar plasmas. The ion current and the root mean square rf voltage on the wafer stage, which are measured using a commercial impedance meter connected to the wafer stage, are chosen as controlled variables because the positive-ion flux and ion energy incident upon the wafer surface are the key factors that determine the etch rate. Two 13.56 MHz rf generators are used to adjust the inductively coupled plasma power and bias power which control ion density and ion energy, respectively. The adopted HfO{sub 2} etch processing used rather low rf voltage. The ion-current value obtained by the power/voltage method is underestimated, so the neural-network model was developed to assist estimating the correct ion-current value. The experimental results show that the etch-rate variation of the closed-loop control is smaller than that of the open-loop control. However, the first wafer effect cannot be eliminated using closed-loop control and thus to achieve a constant etch rate, the chamber-conditioning procedure is required in this etch processing.

  13. Parametric Multi-Level Tiling of Imperfectly Nested Loops

    SciTech Connect

    Hartono, Albert; Baskaran, Muthu M.; Bastoul, Cedric; Cohen, Albert; Krishnamoorthy, Sriram; Norris, Boyana; Ramanujam, J.; Sadayappan, Ponnuswamy

    2009-05-18

    Tiling is a critical loop transformation for generating high-performance code on modern architectures. Efficient generation of multilevel tiled code is essential to exploit several levels of parallelism and/or to maximize data reuse in deep memory hierarchies. Tiled loops with parameterized tile sizes (not compile time constants) facilitate runtime feedback and dynamic optimizations used in iterative compilation and automatic tuning. The existing parametric multilevel tiling approach has focused on transformation for perfectly nested loops, where all assignment statements are contained inside the innermost loop of a loop nest. Previous solutions to tiling for imperfect loop nests are limited to the case where tile sizes are fixed. In this paper, we present an approach to parameterized multilevel tiling for imperfectly nested loops. Our tiling algorithm generates loops that iterate over full rectangular tiles that are amenable for potential compiler optimizations such as register tiling. Experimental results using a number of computational benchmarks demonstrate the effectiveness of our tiling approach.

  14. Rollercoaster loop shapes

    NASA Astrophysics Data System (ADS)

    Pendrill, Ann-Marie

    2005-11-01

    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.

  15. 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.

  16. 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)

  17. 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.

  18. Multichannel electrotactile feedback for simultaneous and proportional myoelectric control

    NASA Astrophysics Data System (ADS)

    Patel, Gauravkumar K.; Dosen, Strahinja; Castellini, Claudio; Farina, Dario

    2016-10-01

    Objective. Closing the loop in myoelectric prostheses by providing artificial somatosensory feedback to the user is an important need for prosthetic users. Previous studies investigated feedback strategies in combination with the control of one degree of freedom of simple grippers. Modern hands, however, are sophisticated multifunction systems. In this study, we assessed multichannel electrotactile feedback integrated with an advanced method for the simultaneous and proportional control of individual fingers of a dexterous hand. Approach. The feedback used spatial and frequency coding to provide information on the finger positions (normalized flexion angles). A comprehensive set of conditions have been investigated in 28 able-bodied subjects, including feedback modalities (visual, electrotactile and no feedback), control tasks (fingers and grasps), systems (virtual and real hand), control methods (ideal and realistic) and range of motion (low and high). The task for the subjects was to operate the hand using closed-loop myoelectric control and generate the desired movement (e.g., selected finger or grasp at a specific level of closure). Main results. The subjects could perceive the multichannel and multivariable electrotactile feedback and effectively exploit it to improve the control performance with respect to open-loop grasping. The improvement however depended on the reliability of the feedforward control, with less consistent control exhibiting performance trends that were more complex across the conditions. Significance. The results are promising for the potential application of advanced feedback to close the control loop in sophisticated prosthetic systems.

  19. 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).

  20. 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.

  1. Control of conducting polymer actuators without physical feedback: simulated feedback control approach with particle swarm optimization

    NASA Astrophysics Data System (ADS)

    Xiang, Xingcan; Mutlu, Rahim; Alici, Gursel; Li, Weihua

    2014-03-01

    Conducting polymer actuators have shown significant potential in articulating micro instruments, manipulation devices, and robotics. However, implementing a feedback control strategy to enhance their positioning ability and accuracy in any application requires a feedback sensor, which is extremely large in size compared to the size of the actuators. Therefore, this paper proposes a new sensorless control scheme without the use of a position feedback sensor. With the help of the system identification technique and particle swarm optimization, the control scheme, which we call the simulated feedback control system, showed a satisfactory command tracking performance for the conducting polymer actuator’s step and dynamic displacement responses, especially under a disturbance, without needing a physical feedback loop, but using a simulated feedback loop. The primary contribution of this study is to propose and experimentally evaluate the simulated feedback control scheme for a class of the conducting polymer actuators known as tri-layer polymer actuators, which can operate both in dry and wet media. This control approach can also be extended to other smart actuators or systems, for which the feedback control based on external sensing is impractical.

  2. 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

  3. 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.

  4. Programmable high voltage power supply with regulation confined to the high voltage section

    NASA Astrophysics Data System (ADS)

    Castell, Karen D.; Ruitberg, Arthur P.

    1994-11-01

    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.

  5. A zero-voltage switching technique for minimizing the current-source power of implanted stimulators.

    PubMed

    Çilingiroğlu, Uğur; İpek, Sercan

    2013-08-01

    The current-source power of an implanted stimulator is reduced almost to the theoretical minimum by driving the electrodes directly from the secondary port of the inductive link with a dedicated zero-voltage switching power supply. A feedback loop confined to the secondary of the inductive link adjusts the timing and conduction angle of switching to provide just the right amount of supply voltage needed for keeping the current-source voltage constant at or slightly above the compliance limit. Since drive is based on current rather than voltage, and supply-voltage update is near real-time, the quality of the current pulses is high regardless of how the electrode impedance evolves during stimulation. By scaling the switching frequency according to power demand, the technique further improves overall power consumption of the stimulator. The technique is implemented with a very simple control circuitry comprising a comparator, a Schmitt trigger and a logic gate of seven devices in addition to an on-chip switch and an off-chip capacitor. The power consumed by the proposed supply circuit itself is no larger than what the linear regulator of a conventional supply typically consumes for the same stimulation current. Still, the sum of supply and current-source power is typically between 20% and 75% of the conventional source power alone. Functionality of the proposed driver is verified experimentally on a proof-of-concept prototype built with 3.3 V devices in a 0.18 μm CMOS technology. PMID:23893206

  6. 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.

  7. Sweep aided Costas loop acquisition of a spread spectrum signal

    NASA Astrophysics Data System (ADS)

    Amoroso, F.

    When a Costas loop must acquire a DSPN spread spectrum signal over a large frequency uncertainty a sweep voltage aid may be introduced into the loop to drive the VCO over the range of uncertainty. This paper treats the problems of acquiring synchronism to the PN stream, sensing the proximity of the target frequency, and freezing the sweep voltage so that the loop is not stressed as it locks onto the received signal. The questions of and false alarm and false dismissal in sensing the proximity of the target are treated theoretically and by computer simulation. The simulation results illustrate the acquisition and lock process, and give statistical performance data.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. All-electronic droplet generation on-chip with real-time feedback control for EWOD digital microfluidics.

    PubMed

    Gong, Jian; Kim, Chang-Jin C J

    2008-06-01

    Electrowetting-on-dielectric (EWOD) actuation enables digital (or droplet) microfluidics where small packets of liquids are manipulated on a two-dimensional surface. Due to its mechanical simplicity and low energy consumption, EWOD holds particular promise for portable systems. To improve volume precision of the droplets, which is desired for quantitative applications such as biochemical assays, existing practices would require near-perfect device fabrication and operation conditions unless the droplets are generated under feedback control by an extra pump setup off of the chip. In this paper, we develop an all-electronic (i.e., no ancillary pumping) real-time feedback control of on-chip droplet generation. A fast voltage modulation, capacitance sensing, and discrete-time PID feedback controller are integrated on the operating electronic board. A significant improvement is obtained in the droplet volume uniformity, compared with an open loop control as well as the previous feedback control employing an external pump. Furthermore, this new capability empowers users to prescribe the droplet volume even below the previously considered minimum, allowing, for example, 1 : x (x < 1) mixing, in comparison to the previously considered n : m mixing (i.e., n and m unit droplets).

  13. ALL-ELECTRONIC DROPLET GENERATION ON-CHIP WITH REAL-TIME FEEDBACK CONTROL FOR EWOD DIGITIAL MICROFLUIDICS

    PubMed Central

    Gong, Jian; Kim, Chang-Jin “CJ”

    2009-01-01

    Electrowetting-on-dielectric (EWOD) actuation enables digital (or droplet) microfluidics where small packets of liquids are manipulated on a two-dimensional surface. Due to its mechanical simplicity and low energy consumption, EWOD holds particular promise for portable systems. To improve volume precision of the droplets, which is desired for quantitative applications such as biochemical assays, existing practices would require near-perfect device fabricaion and operation conditions unless the droplets are generated under feedback control by an extra pump setup off of the chip. In this paper, we develop an all-electronic (i.e., no ancillary pumping) real-time feedback control of on-chip droplet generation. A fast voltage modulation, capacitance sensing, and discrete-time PID feedback controller are integrated on the operating electronic board. A significant improvement is obtained in the droplet volume uniformity, compared with an open loop control as well as the previous feedback control employing an external pump. Furthermore, this new capability empowers users to prescribe the droplet volume even below the previously considered minimum, allowing, for example, 1:x (x < 1) mixing, in comparison to the previously considered n:m mixing (i.e., n and m unit droplets). PMID:18497909

  14. 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.

  15. Look before You Loop.

    ERIC Educational Resources Information Center

    Bellis, Marilyn

    1999-01-01

    Explores looping, which involves one teacher staying with the same group of children for more than one year. Recognizes that, with today's changing demographics, looping can be a way to foster a family-like classroom atmosphere. Discusses advantages and disadvantages to looping. Includes a chart of looping opportunities and considerations;…

  16. Feedbacks in human-landscape systems.

    PubMed

    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.

  17. 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.

  18. 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.

  19. A cryo-amplifier working in a double loop-flux locked loop scheme for SQUID readout of TES detectors

    NASA Astrophysics Data System (ADS)

    Torrioli, Guido; Bastia, Paolo; Piro, Luigi; Macculi, Claudio; Colasanti, Luca

    2010-07-01

    In this paper we report on a novel SQUID readout scheme, called Double Loop-Flux Locked loop (DL-FLL), that we are investigating in the frame of ASI and ESA technological development contracts. This scheme is based on the realization of a cryogenic amplifier which is used in order to readout TES detectors in the Frequency Division Multiplexing technique, where high loop-gain is required up to few MHz. Loop-gain in feedback systems is, usually, limited by the propagation delay of the signals traveling in the loop because of the distance between the feedback loop elements. This problem is particularly evident in the case of SQUID systems, where the elements of the feedback loop are placed both at cryogenic and room temperature. To solve this issue we propose a low power dissipation cryo-amplifier capable to work at cryogenic temperatures so that it can be placed close to the SQUID realizing a local cryogenic loop. The adoption of the DL-FLL scheme allows to simplify considerably the cryo-amplifier which, being AC-coupled, don't require the features of a precision DC-coupled amplifier and can be made with a limited number of electronic components and with a consequent reduction of power dissipation.

  20. OPE for super loops

    NASA Astrophysics Data System (ADS)

    Sever, Amit; Vieira, Pedro; Wang, Tianheng

    2011-11-01

    We extend the Operator Product Expansion for Null Polygon Wilson loops to the Mason-Skinner-Caron-Huot super loop dual to non MHV gluon amplitudes. We explain how the known tree level amplitudes can be promoted into an infinite amount of data at any loop order in the OPE picture. As an application, we re-derive all one loop NMHV six gluon amplitudes by promoting their tree level expressions. We also present some new all loops predictions for these amplitudes.

  1. 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.

  2. 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.

  3. Voltage tunable polymer laser device

    NASA Astrophysics Data System (ADS)

    Döring, Sebastian; Kollosche, Matthias; Rabe, Torsten; Kofod, Guggi; Stumpe, Joachim

    2012-03-01

    Since organic laser materials offer broad optical gain spectra they are predestined for the realization of widely tunable laser sources. Here we report on a compact organic laser device that allows for voltage controlled continuously wavelength tuning in the visible range of the spectrum by external deformation. The device consists of an elastomeric distributed feedback (DFB) laser and an electro-active elastomer actuator also known as artificial muscle. Second order DFB lasing is realized by a grating line structured elastomer substrate covered with a thin layer of dye doped polymer. To enable wavelength tuning the elastomer laser is placed at the center of the electro-active elastomer actuator. Chosen design of the actuator gives rise to homogeneous compression at this position. The voltage induced deformation of the artificial muscle is transferred to the elastomer laser and results in a decrease of grating period. This leads to an emission wavelength shift of the elastomer laser. The increase of actuation voltage to 3.25 kV decreased the emission wavelength from 604 nm to 557 nm, a change of 47 nm or 7.8%.

  4. 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.

  5. 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.

    PubMed

    Calabrese, G; Capineri, L; Granato, M; Frattini, G

    2015-04-01

    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.

  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. On the application of frequency selective common mode feedback for multifrequency EIT.

    PubMed

    Langlois, Peter J; Wu, Yu; Bayford, Richard H; Demosthenous, Andreas

    2015-06-01

    Common mode voltages are frequently a problem in electrical impedance tomography (EIT) and other bioimpedance applications. To reduce their amplitude common mode feedback is employed. Formalised analyses of both current and voltage feedback is presented in this paper for current drives. Common mode effects due to imbalances caused by the current drives, the electrode connections to the body load and the introduction of the body impedance to ground are considered. Frequency selective narrowband common mode feedback previously proposed to provide feedback stability is examined. As a step towards multifrequency applications the use of narrowband feedback is experimentally demonstrated for two simultaneous current drives. Measured results using standard available components show a reduction of 62 dB for current feedback and 31 dB for voltage feedback. Frequencies ranged from 50 kHz to 1 MHz.

  8. 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.

  9. 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.

  10. Batteries: Widening voltage windows

    NASA Astrophysics Data System (ADS)

    Xu, Kang; Wang, Chunsheng

    2016-10-01

    The energy output of aqueous batteries is largely limited by the narrow voltage window of their electrolytes. Now, a hydrate melt consisting of lithium salts is shown to expand such voltage windows, leading to a high-energy aqueous battery.

  11. 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…

  12. 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.

  13. 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.

  14. Distinct noise-controlling roles of multiple negative feedback mechanisms in a prokaryotic operon system.

    PubMed

    Nguyen, L K; Kulasiri, D

    2011-03-01

    Molecular fluctuations are known to affect dynamics of cellular systems in important ways. Studies aimed at understanding how molecular systems of certain regulatory architectures control noise therefore become essential. The interplay between feedback regulation and noise has been previously explored for cellular networks governed by a single negative feedback loop. However, similar issues within networks consisting of more complex regulatory structures remain elusive. The authors investigate how negative feedback loops manage noise within a biochemical cascade concurrently governed by multiple negative feedback loops, using the prokaryotic tryptophan (trp) operon system in Escherechia coli as the model system. To the authors knowledge, this is the first study of noise in the trp operon system. They show that the loops in the trp operon system possess distinct, even opposing, noise-controlling effects despite their seemingly analogous feedback structures. The enzyme inhibition loop, although controlling the last reaction of the cascade, was found to suppress noise not only for the tryptophan output but also for other upstream components. In contrast, the Repression (Rep) loop enhances noise for all systems components. Attenuation (Att) poses intermediate effects by attenuating noise for the upstream components but promoting noise for components downstream of its target. Regarding noise at the output tryptophan, Rep and Att can be categorised as noise-enhancing loops whereas Enzyme Inhibition as a noise-reducing loop. These findings suggest novel implications in how cellular systems with multiple feedback mechanisms control noise. [Includes supplementary material]. PMID:21405203

  15. Feedback from horizontal cells to rod photoreceptors in vertebrate retina

    PubMed Central

    Thoreson, Wallace B.; Babai, Norbert; Bartoletti, Theodore M.

    2013-01-01

    Retinal horizontal cells (HCs) provide negative feedback to cones but, largely because annular illumination fails to evoke a depolarizing response in rods, it is widely believed that there is no feedback from HCs to rods. However, feedback from HCs to cones involves small changes in the calcium current (ICa) that does not always generate detectable depolarizing responses. We therefore recorded ICa directly from rods to test whether they were modulated by feedback from HCs. To circumvent problems presented by overlapping receptive fields of HCs and rods, we manipulated the membrane potential of voltage clamped HCs while simultaneously recording from rods in a salamander retinal slice preparation. Like HC feedback in cones, hyperpolarizing HCs from −14 to −54, −84, and −104 mV increased the amplitude of ICa recorded from synaptically connected rods and caused hyperpolarizing shifts in ICa voltage dependence. These effects were blocked by supplementing the bicarbonate-buffered saline solution with HEPES. In rods lacking light-responsive outer segments, hyperpolarizing neighboring HCs with light caused a negative activation shift and increased the amplitude of ICa. These changes in ICa were blocked by HEPES and by inhibiting HC light responses with a glutamate antagonist indicating they were due to HC feedback. These results show that rods, like cones, receive negative feedback from HCs that regulates the amplitude and voltage dependence of ICa. HC to rod feedback counters light-evoked decreases in synaptic output and thus shapes the transmission of rod responses to downstream visual neurons. PMID:18509030

  16. 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.

  17. Closed-loop control of ionization oscillations in Hall accelerators

    SciTech Connect

    Barral, S.; Kaczmarczyk, J.; Kurzyna, J.; Dudeck, M.

    2011-08-15

    Feedback control of ionization oscillations in Hall accelerators is investigated with a proportional-integral-derivative controller acting on the discharge voltage. The stability of the current is found to systematically improve with proportional control, whereas integral and derivative control have in most cases a detrimental or insignificant impact. At low discharge voltages, proportional control eliminates at the same time ionization breathing oscillations as well as a coexisting low frequency mode. A progressive deterioration of the stability is observed at higher voltage, presumably attributable to the limited output voltage range of the controller. The time-averaged characteristics of the discharge such as average current, thrust and efficiency, remain unchanged within measurement uncertainties.

  18. High Voltage SPT Performance

    NASA Technical Reports Server (NTRS)

    Manzella, David; Jacobson, David; Jankovsky, Robert

    2001-01-01

    A 2.3 kW stationary plasma thruster designed to operate at high voltage was tested at discharge voltages between 300 and 1250 V. Discharge specific impulses between 1600 and 3700 sec were demonstrated with thrust between 40 and 145 mN. Test data indicated that discharge voltage can be optimized for maximum discharge efficiency. The optimum discharge voltage was between 500 and 700 V for the various anode mass flow rates considered. The effect of operating voltage on optimal magnet field strength was investigated. The effect of cathode flow rate on thruster efficiency was considered for an 800 V discharge.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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…

  4. Effects of unwanted feedback on synchronized chaotic optical communications

    NASA Astrophysics Data System (ADS)

    Li, Xiaofeng; Pan, Wei; Luo, Bin; Ma, Dong

    2006-04-01

    The effects of unwanted external optical feedback on synchronized chaotic optical communication systems are studied numerically. We consider an open-loop configuration consisting of a transmitter laser with double external optical feedbacks and a receiver laser with optical injection from the transmitter laser. First, including the effects of unwanted optical feedback, the synchronization performances of both the complete synchronization and the generalized synchronization are examined. Then the encoding and decoding performances of the generalized synchronization and the effects of the introduced feedback are investigated, respectively. Finally, we study the control of the unwanted feedback on the dynamics of the transmitter laser and briefly discuss the system security when the transmitter laser is driven to operate in a steady state or periodic oscillation state by the additional feedback.

  5. Remote feedback stabilization of tokamak instabilities

    SciTech Connect

    Sen, A.K. )

    1994-05-01

    A novel remote suppressor consisting of an injected ion beam has been used for the stabilization of plasma instabilities. A collisionless curvature-driven trapped-particle instability, an [bold E][times][bold B] flute mode and an ion temperature gradient (ITG) instability have been successfully suppressed down to noise levels using this scheme. Furthermore, the first experimental demonstration of a multimode feedback stabilization with a single sensor--suppressor pair has been achieved. Two modes (an [bold E][times][bold B] flute and an ITG mode) were simultaneously stabilized with a simple state-feedback-type method where more state'' information was generated from a single-sensor Langmuir probe by appropriate signal processing. The above experiments may be considered as paradigms for controlling several important tokamak instabilities. First, feedback suppression of edge fluctuations in a tokamak with a suitable form of insulated segmented poloidal limiter sections used as Langmuir-probe-like suppressors is proposed. Other feedback control schemes are proposed for the suppression of electrostatic core fluctuations via appropriately phased ion density input from a modulated neutral beam. Most importantly, a scheme to control major disruptions in tokamaks via feedback suppression of kink (and possibly) tearing modes is discussed. This may be accomplished by using a modulated neutral beam suppressor in a feedback loop, which will supply a momentum input of appropriate phase and amplitude. Simple theoretical models predict modest levels of beam energy, current, and power.

  6. Phase-Locked Loop Noise Reduction via Phase Detector Implementation for Single-Phase Systems

    SciTech Connect

    Thacker, Timothy; Boroyevich, Dushan; Burgos, Rolando; Wang, Fei

    2011-01-01

    A crucial component of grid-connected converters is the phase-locked loop (PLL) control subsystem that tracks the grid voltage's frequency and phase angle. Therefore, accurate fast-responding PLLs for control and protection purposes are required to provide these measurements. This paper proposes a novel feedback mechanism for single-phase PLL phase detectors using the estimated phase angle. Ripple noise appearing in the estimated frequency, most commonly the second harmonic under phase-lock conditions, is reduced or eliminated without the use of low-pass filters, which can cause delays to occur and limits the overall performance of the PLL response to dynamic changes in the system. The proposed method has the capability to eliminate the noise ripple entirely and, under extreme line distortion conditions, can reduce the ripple by at least half. Other modifications implemented through frequency feedback are shown to decrease the settling time of the PLL up to 50%. Mathematical analyses with the simulated and experimental results are provided to confirm the validity of the proposed methods.

  7. Bringing Students into the Loop: A Faculty Feedback Program

    ERIC Educational Resources Information Center

    Blumner, Jacob; Fritz, Francis; Wice, Sarah

    2007-01-01

    This article describes a model for student/faculty collaboration in WAC development--students tutoring faculty on drafts of the writing assignments they have designed for their own students. While writing center scholarship is student-centered and invites student participation, Writing Across the Curriculum scholarship and implementation remains…

  8. Regulation of pollen tube polarity: Feedback loops rule

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Targeted delivery of immotile sperm through growing pollen tubes is a crucial step in achieving sexual reproduction in angiosperms. Unlike diffuse-growing cells, the growth of a pollen tube is restricted to the very apical region where targeted exocytosis and regulated endocytosis occur. The plant-s...

  9. Tectonic stress feedback loop explains U-shaped glacial valleys

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2014-03-01

    In the shadow of the Matterhorn, the broad form of the Matter Valley—like so many throughout the Alps—is interrupted by a deep U-shaped glacial trough. Carved into a landscape reflecting millennia of tectonic uplift and river erosion, growing evidence suggests the 100-meter-deep U-shaped groove was produced shortly after a shift toward major cycles of Alpine glaciation almost a million years ago. Subsequent glaciations may have therefore had little effect on the landscape.

  10. Apparatus for externally controlled closed-loop feedback digital epitaxy

    DOEpatents

    Eres, D.; Sharp, J.W.

    1996-07-30

    A method and apparatus for digital epitaxy are disclosed. The apparatus includes a pulsed gas delivery assembly that supplies gaseous material to a substrate to form an adsorption layer of the gaseous material on the substrate. Structure is provided for measuring the isothermal desorption spectrum of the growth surface to monitor the active sites which are available for adsorption. The vacuum chamber housing the substrate facilitates evacuation of the gaseous material from the area adjacent the substrate following exposure. In use, digital epitaxy is achieved by exposing a substrate to a pulse of gaseous material to form an adsorption layer of the material on the substrate. The active sites on the substrate are monitored during the formation of the adsorption layer to determine if all the active sites have been filled. Once the active sites have been filled on the growth surface of the substrate, the pulse of gaseous material is terminated. The unreacted portion of the gas pulse is evacuated by continuous pumping. Subsequently, a second pulse is applied when availability of active sites is determined by studying the isothermal desorption spectrum. These steps are repeated until a thin film of sufficient thickness is produced. 5 figs.

  11. Apparatus for externally controlled closed-loop feedback digital epitaxy

    DOEpatents

    Eres, Djula; Sharp, Jeffrey W.

    1996-01-01

    A method and apparatus for digital epitaxy. The apparatus includes a pulsed gas delivery assembly that supplies gaseous material to a substrate to form an adsorption layer of the gaseous material on the substrate. Structure is provided for measuring the isothermal desorption spectrum of the growth surface to monitor the active sites which are available for adsorption. The vacuum chamber housing the substrate facilitates evacuation of the gaseous material from the area adjacent the substrate following exposure. In use, digital epitaxy is achieved by exposing a substrate to a pulse of gaseous material to form an adsorption layer of the material on the substrate. The active sites on the substrate are monitored during the formation of the adsorption layer to determine if all the active sites have been filled. Once the active sites have been filled on the growth surface of the substrate, the pulse of gaseous material is terminated. The unreacted portion of the gas pulse is evacuated by continuous pumping. Subsequently, a second pulse is applied when availability of active sites is determined by studying the isothermal desorption spectrum. These steps are repeated until a thin film of sufficient thickness is produced.

  12. The generalized pole assignment problem. [dynamic output feedback control systems

    NASA Technical Reports Server (NTRS)

    Djaferis, T. E.; Mitter, S. K.

    1979-01-01

    For some linear, strictly proper system given by its transfer function, two dynamic output feedback problems can be posed. The first one is that of using dynamic-output feedback to assign the closed-loop characteristic polynomial and the second that of assigning the closed-loop invariant factors. These problems and their interrelationships are discussed. The formulation is done in the frequency domain and the investigation carried out from an algebraic point of view, in terms of linear equations over rings of polynomials. Using the notion of genericity, several necessary and sufficient conditions are expressed.

  13. Operation of the PEP transverse beam feedback

    SciTech Connect

    Olson, C.W.; Paterson, J.M.; Pellegrin, J.L.; Rees, J.R.

    1981-02-01

    The PEP Storage Ring has been equipped with a wide band beam feedback system capable of damping the vertical and horizontal motion of six bunches. The oscillation detection is done at a symmetry point on the Storage Ring and feedback is applied at the same location one orbital period later. The signal is synchronously gated and the system appears as twelve independent feedback loops, operating on the two coordinates of each of the six bunches. Two beam deflection electrodes are driven each by a low-Q push-pull amplifier which is tuned at the 72nd harmonic of the revolution frequency and suppressed-carrier modulation is generated by a sequence of the detected bunch oscillations. The design parameters are reviewed as well as the salient features of the hardware, and the impact of this system on the machine operation is evaluated in the light of experimental results.

  14. An optimal open/closed-loop control method with application to a pre-stressed thin duralumin plate

    NASA Astrophysics Data System (ADS)

    Nadimpalli, Sruthi Raju

    The excessive vibrations of a pre-stressed duralumin plate, suppressed by a combination of open-loop and closed-loop controls, also known as open/closed-loop control, is studied in this thesis. The two primary steps involved in this process are: Step (I) with an assumption that the closed-loop control law is proportional, obtain the optimal open-loop control by direct minimization of the performance measure consisting of energy at terminal time and a penalty on open-loop control force via calculus of variations. If the performance measure also involves a penalty on closed-loop control effort then a Fourier based method is utilized. Step (II) the energy at terminal time is minimized numerically to obtain optimal values of feedback gains. The optimal closed-loop control gains obtained are used to describe the displacement and the velocity of open-loop, closed-loop and open/closed-loop controlled duralumin plate.

  15. Chromaticity Feedback at RHIC

    SciTech Connect

    Marusic, A.; Minty, M.; Tepikian, S.

    2010-05-23

    Chromaticity feedback during the ramp to high beam energies has been demonstrated in the Relativistic Heavy Ion Collider (RHIC). In this report we review the feedback design and measurement technique. Commissioning experiences including interaction with existing tune and coupling feedback are presented together with supporting experimental data.

  16. The Mythology of Feedback

    ERIC Educational Resources Information Center

    Adcroft, Andy

    2011-01-01

    Much of the general education and discipline-specific literature on feedback suggests that it is a central and important element of student learning. This paper examines feedback from a social process perspective and suggests that feedback is best understood through an analysis of the interactions between academics and students. The paper argues…

  17. Preventing Feedback Fizzle

    ERIC Educational Resources Information Center

    Brookhart, Susan M.

    2012-01-01

    Feedback is certainly about saying or writing helpful, learning-focused comments. But that is only part of it. What happens beforehand? What happens afterward? Feedback that is helpful and learning-focused fits into a context. Before a teacher gives feedback, students need to know the learning target so they have a purpose for using the feedback…

  18. Developing Sustainable Feedback Practices

    ERIC Educational Resources Information Center

    Carless, David; Salter, Diane; Yang, Min; Lam, Joy

    2011-01-01

    Feedback is central to the development of student learning, but within the constraints of modularized learning in higher education it is increasingly difficult to handle effectively. This article makes a case for sustainable feedback as a contribution to the reconceptualization of feedback processes. The data derive from the Student Assessment and…

  19. Feedback control of plasma electron density and ion energy in an inductively coupled plasma etcher

    SciTech Connect

    Lin Chaung; Leou, K.-C.; Huang, H.-M.; Hsieh, C.-H.

    2009-01-15

    Here the authors report the development of a fuzzy logic based feedback control of the plasma electron density and ion energy for high density plasma etch process. The plasma electron density was measured using their recently developed transmission line microstrip microwave interferometer mounted on the chamber wall, and the rf voltage was measured by a commercial impedance meter connected to the wafer stage. The actuators were two 13.56 MHz rf power generators which provided the inductively coupled plasma power and bias power, respectively. The control system adopted the fuzzy logic control algorithm to reduce frequent actuator action resulting from measurement noise. The experimental results show that the first wafer effect can be eliminated using closed-loop control for both poly-Si and HfO{sub 2} etching. In particular, for the HfO2 etch, the controlled variables in this work were much more effective than the previous one where ion current was controlled, instead of the electron density. However, the pressure disturbance effect cannot be reduced using plasma electron density feedback.

  20. Feedbacks in human-landscape systems.

    PubMed

    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. PMID:23592016

  1. Voltage verification unit

    DOEpatents

    Martin, Edward J.

    2008-01-15

    A voltage verification unit and method for determining the absence of potentially dangerous potentials within a power supply enclosure without Mode 2 work is disclosed. With this device and method, a qualified worker, following a relatively simple protocol that involves a function test (hot, cold, hot) of the voltage verification unit before Lock Out/Tag Out and, and once the Lock Out/Tag Out is completed, testing or "trying" by simply reading a display on the voltage verification unit can be accomplished without exposure of the operator to the interior of the voltage supply enclosure. According to a preferred embodiment, the voltage verification unit includes test leads to allow diagnostics with other meters, without the necessity of accessing potentially dangerous bus bars or the like.

  2. Coherent feedback control of a single qubit in diamond

    NASA Astrophysics Data System (ADS)

    Hirose, Masashi; Cappellaro, Paola

    2016-04-01

    Engineering desired operations on qubits subjected to the deleterious effects of their environment is a critical task in quantum information processing, quantum simulation and sensing. The most common approach relies on open-loop quantum control techniques, including optimal-control algorithms based on analytical or numerical solutions, Lyapunov design and Hamiltonian engineering. An alternative strategy, inspired by the success of classical control, is feedback control. Because of the complications introduced by quantum measurement, closed-loop control is less pervasive in the quantum setting and, with exceptions, its experimental implementations have been mainly limited to quantum optics experiments. Here we implement a feedback-control algorithm using a solid-state spin qubit system associated with the nitrogen vacancy centre in diamond, using coherent feedback to overcome the limitations of measurement-based feedback, and show that it can protect the qubit against intrinsic dephasing noise for milliseconds. In coherent feedback, the quantum system is connected to an auxiliary quantum controller (ancilla) that acquires information about the output state of the system (by an entangling operation) and performs an appropriate feedback action (by a conditional gate). In contrast to open-loop dynamical decoupling techniques, feedback control can protect the qubit even against Markovian noise and for an arbitrary period of time (limited only by the coherence time of the ancilla), while allowing gate operations. It is thus more closely related to quantum error-correction schemes, although these require larger and increasing qubit overheads. Increasing the number of fresh ancillas enables protection beyond their coherence time. We further evaluate the robustness of the feedback protocol, which could be applied to quantum computation and sensing, by exploring a trade-off between information gain and decoherence protection, as measurement of the ancilla-qubit correlation

  3. Coherent feedback control of a single qubit in diamond.

    PubMed

    Hirose, Masashi; Cappellaro, Paola

    2016-04-01

    Engineering desired operations on qubits subjected to the deleterious effects of their environment is a critical task in quantum information processing, quantum simulation and sensing. The most common approach relies on open-loop quantum control techniques, including optimal-control algorithms based on analytical or numerical solutions, Lyapunov design and Hamiltonian engineering. An alternative strategy, inspired by the success of classical control, is feedback control. Because of the complications introduced by quantum measurement, closed-loop control is less pervasive in the quantum setting and, with exceptions, its experimental implementations have been mainly limited to quantum optics experiments. Here we implement a feedback-control algorithm using a solid-state spin qubit system associated with the nitrogen vacancy centre in diamond, using coherent feedback to overcome the limitations of measurement-based feedback, and show that it can protect the qubit against intrinsic dephasing noise for milliseconds. In coherent feedback, the quantum system is connected to an auxiliary quantum controller (ancilla) that acquires information about the output state of the system (by an entangling operation) and performs an appropriate feedback action (by a conditional gate). In contrast to open-loop dynamical decoupling techniques, feedback control can protect the qubit even against Markovian noise and for an arbitrary period of time (limited only by the coherence time of the ancilla), while allowing gate operations. It is thus more closely related to quantum error-correction schemes, although these require larger and increasing qubit overheads. Increasing the number of fresh ancillas enables protection beyond their coherence time. We further evaluate the robustness of the feedback protocol, which could be applied to quantum computation and sensing, by exploring a trade-off between information gain and decoherence protection, as measurement of the ancilla-qubit correlation

  4. Stability, gain, and robustness in quantum feedback networks

    SciTech Connect

    D'Helon, C.; James, M. R.

    2006-05-15

    In this paper we are concerned with the problem of stability for quantum feedback networks. We demonstrate in the context of quantum optics how stability of quantum feedback networks can be guaranteed using only simple gain inequalities for network components and algebraic relationships determined by the network. Quantum feedback networks are shown to be stable if the loop gain is less than one--this is an extension of the famous small gain theorem of classical control theory. We illustrate the simplicity and power of the small gain approach with applications to important problems of robust stability and robust stabilization.

  5. Portable Dextrous Force Feedback Master for robot telemanipulation (PDMFF)

    NASA Technical Reports Server (NTRS)

    Burdea, Grigore C.; Speeter, Thomas H.

    1989-01-01

    A major drawback of open loop masters is a lack of force feedback, limiting their ability to perform complex tasks such as assembly and repair. Researchers present a simple dextrous force feedback master for computer assisted telemanipulation. The device is compact, portable and can be held in the operator hand, without the need for a special joystick or console. The system is capable of both position feed forward and force feedback, using electronic position sensors and a pneumatic micro-actuator. The level of forces exercised by the pneumatic actuator is such that near rigidity may be attained. Experimental results showing good system linearity and small time lag are given.

  6. RF power recovery feedback circulator

    DOEpatents

    Sharamentov, Sergey I.

    2011-03-29

    A device and method for improving the efficiency of RF systems having a Reflective Load. In the preferred embodiment, Reflected Energy from a superconducting resonator of a particle accelerator is reintroduced to the resonator after the phase of the Reflected Energy is aligned with the phase of the Supply Energy from a RF Energy Source. In one embodiment, a Circulator is used to transfer Reflected Energy from the Reflective Load into a Phase Adjuster which aligns the phase of the Reflected Energy with that of the Supply Energy. The phase-aligned energy is then combined with the Supply Energy, and reintroduced into the Reflective Load. In systems having a constant phase shift, the Phase Adjuster may be designed to shift the phase of the Reflected Energy by a constant amount using a Phase Shifter. In systems having a variety (variable) phase shifts, a Phase Shifter controlled by a phase feedback loop comprising a Phase Detector and a Feedback Controller to account for the various phase shifts is preferable.

  7. Simulation of the fast steering mirror control system based on gyro velocity feedback

    NASA Astrophysics Data System (ADS)

    Kuang, Jiagming; Tang, Tao; Fu, Chengyu; Ding, Ke; Yu, Wei

    2009-11-01

    The fast steering mirror is a significant element of the photoelectric precision tracking system and is mainly used for attenuating the tracking error of the main axis and rejecting the line-of-sight jitter caused by various disturbances. A control loop model is constructed and object parameters have been identified according to this model in this paper. Low sampling frequency introduce great delay into the imaging tracking system, which may restrict greatly the closed-loop bandwidth, reduce tracking precision of the system and even make the system unsteady. Various elements which limit tracking loop bandwidth are presented and analyzed. Three tracking systems with different sampling frequency are simulated and analyzed. From the simulation result the conclusion can be drawn that it is difficult to increase the closedloop bandwidth in the presence of great delay by means of the general control method. Accordingly feedback control or feed forward control may be tried to improve the error attenuation of the system. The micro-mechanical gyro can be used for measuring the angular velocity of fast steering mirror, so output of velocity gyro as velocity loop feedback may improve the system performance. Furthermore, the velocity loop feedback can enhance the rigidity and the output stability of the tracking system. Finally, the velocity feedback can increase the type of the open loop system; consequently it will improve the error attenuation of the system. The simulation result shows that the tracking precision of the system with velocity feedback is 10 times better than the system without velocity feedback.

  8. Voltage balanced multilevel voltage source converter system

    DOEpatents

    Peng, Fang Zheng; Lai, Jih-Sheng

    1997-01-01

    A voltage balanced multilevel converter for high power AC applications such as adjustable speed motor drives and back-to-back DC intertie of adjacent power systems. This converter provides a multilevel rectifier, a multilevel inverter, and a DC link between the rectifier and the inverter allowing voltage balancing between each of the voltage levels within the multilevel converter. The rectifier is equipped with at least one phase leg and a source input node for each of the phases. The rectifier is further equipped with a plurality of rectifier DC output nodes. The inverter is equipped with at least one phase leg and a load output node for each of the phases. The inverter is further equipped with a plurality of inverter DC input nodes. The DC link is equipped with a plurality of rectifier charging means and a plurality of inverter discharging means. The plurality of rectifier charging means are connected in series with one of the rectifier charging means disposed between and connected in an operable relationship with each adjacent pair of rectifier DC output nodes. The plurality of inverter discharging means are connected in series with one of the inverter discharging means disposed between and connected in an operable relationship with each adjacent pair of inverter DC input nodes. Each of said rectifier DC output nodes are individually electrically connected to the respective inverter DC input nodes. By this means, each of the rectifier DC output nodes and each of the inverter DC input nodes are voltage balanced by the respective charging and discharging of the rectifier charging means and the inverter discharging means.

  9. Voltage balanced multilevel voltage source converter system

    DOEpatents

    Peng, F.Z.; Lai, J.S.

    1997-07-01

    Disclosed is a voltage balanced multilevel converter for high power AC applications such as adjustable speed motor drives and back-to-back DC intertie of adjacent power systems. This converter provides a multilevel rectifier, a multilevel inverter, and a DC link between the rectifier and the inverter allowing voltage balancing between each of the voltage levels within the multilevel converter. The rectifier is equipped with at least one phase leg and a source input node for each of the phases. The rectifier is further equipped with a plurality of rectifier DC output nodes. The inverter is equipped with at least one phase leg and a load output node for each of the phases. The inverter is further equipped with a plurality of inverter DC input nodes. The DC link is equipped with a plurality of rectifier charging means and a plurality of inverter discharging means. The plurality of rectifier charging means are connected in series with one of the rectifier charging means disposed between and connected in an operable relationship with each adjacent pair of rectifier DC output nodes. The plurality of inverter discharging means are connected in series with one of the inverter discharging means disposed between and connected in an operable relationship with each adjacent pair of inverter DC input nodes. Each of said rectifier DC output nodes are individually electrically connected to the respective inverter DC input nodes. By this means, each of the rectifier DC output nodes and each of the inverter DC input nodes are voltage balanced by the respective charging and discharging of the rectifier charging means and the inverter discharging means. 15 figs.

  10. Closed-loop structural stability for linear-quadratic optimal systems

    NASA Technical Reports Server (NTRS)

    Wong, P. K.; Athans, M.

    1975-01-01

    This paper contains an explicit parameterization of a subclass of linear constant gain feedback maps that never destabilize an originally open-loop stable system. These results can then be used to obtain several new structural stability results for multi-input linear-quadratic feedback optimal designs.

  11. Low voltage to high voltage level shifter and related methods

    NASA Technical Reports Server (NTRS)

    Mentze, Erik J. (Inventor); Hess, Herbert L. (Inventor); Buck, Kevin M. (Inventor); Cox, David F. (Inventor)

    2006-01-01

    A shifter circuit comprises a high and low voltage buffer stages and an output buffer stage. The high voltage buffer stage comprises multiple transistors arranged in a transistor stack having a plurality of intermediate nodes connecting individual transistors along the stack. The transistor stack is connected between a voltage level being shifted to and an input voltage. An inverter of this stage comprises multiple inputs and an output. Inverter inputs are connected to a respective intermediate node of the transistor stack. The low voltage buffer stage has an input connected to the input voltage and an output, and is operably connected to the high voltage buffer stage. The low voltage buffer stage is connected between a voltage level being shifted away from and a lower voltage. The output buffer stage is driven by the outputs of the high voltage buffer stage inverter and the low voltage buffer stage.

  12. Vicious circles: positive feedback in major evolutionary and ecological transitions.

    PubMed

    Crespi, Bernard J

    2004-12-01

    Evolutionary biologists and ecologists often focus on equilibrium states that are subject to forms of negative feedback, such as optima for phenotypic traits or regulation of population sizes. However, recent theoretical and empirical studies show how positive feedback can be instrumental in driving many of the most important and spectacular processes in evolutionary ecology, including the evolution of sex and genetic systems, mating systems, life histories, complex cooperation in insects and humans, ecological specialization, species diversity, species ranges, speciation and extinction. Taken together, this work suggests that positive feedback is more common than is generally appreciated, and that its self-reinforcing dynamics generate the conditions for changes that might otherwise be difficult or impossible for selection or other mechanisms to achieve. Testing for positive feedback requires analysing each causal link in feedback loops, tracking genetic, character and population-dynamic changes across generations, and elucidating the conditions that can result in self-reinforcing change.

  13. Voltage-dependent motion of the catalytic region of voltage-sensing phosphatase monitored by a fluorescent amino acid

    PubMed Central

    Sakata, Souhei; Jinno, Yuka; Kawanabe, Akira; Okamura, Yasushi

    2016-01-01

    The cytoplasmic region of voltage-sensing phosphatase (VSP) derives the voltage dependence of its catalytic activity from coupling to a voltage sensor homologous to that of voltage-gated ion channels. To assess the conformational changes in the cytoplasmic region upon activation of the voltage sensor, we genetically incorporated a fluorescent unnatural amino acid, 3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (Anap), into the catalytic region of Ciona intestinalis VSP (Ci-VSP). Measurements of Anap fluorescence under voltage clamp in Xenopus oocytes revealed that the catalytic region assumes distinct conformations dependent on the degree of voltage-sensor activation. FRET analysis showed that the catalytic region remains situated beneath the plasma membrane, irrespective of the voltage level. Moreover, Anap fluorescence from a membrane-facing loop in the C2 domain showed a pattern reflecting substrate turnover. These results indicate that the voltage sensor regulates Ci-VSP catalytic activity by causing conformational changes in the entire catalytic region, without changing their distance from the plasma membrane. PMID:27330112

  14. The role of auditory feedback in sustaining vocal vibrato

    NASA Astrophysics Data System (ADS)

    Leydon, Ciara; Bauer, Jay J.; Larson, Charles R.

    2003-09-01

    Vocal vibrato and tremor are characterized by oscillations in voice fundamental frequency (F0). These oscillations may be sustained by a control loop within the auditory system. One component of the control loop is the pitch-shift reflex (PSR). The PSR is a closed loop negative feedback reflex that is triggered in response to discrepancies between intended and perceived pitch with a latency of ~100 ms. Consecutive compensatory reflexive responses lead to oscillations in pitch every ~200 ms, resulting in ~5-Hz modulation of F0. Pitch-shift reflexes were elicited experimentally in six subjects while they sustained /you/ vowels at a comfortable pitch and loudness. Auditory feedback was sinusoidally modulated at discrete integer frequencies (1 to 10 Hz) with +/-25 cents amplitude. Modulated auditory feedback induced oscillations in voice F0 output of all subjects at rates consistent with vocal vibrato and tremor. Transfer functions revealed peak gains at 4 to 7 Hz in all subjects, with an average peak gain at 5 Hz. These gains occurred in the modulation frequency region where the voice output and auditory feedback signals were in phase. A control loop in the auditory system may sustain vocal vibrato and tremorlike oscillations in voice F0.

  15. The role of auditory feedback in sustaining vocal vibratoa)

    PubMed Central

    Leydon, Ciara; Bauer, Jay J.; Larson, Charles R.

    2006-01-01

    Vocal vibrato and tremor are characterized by oscillations in voice fundamental frequency (F0). These oscillations may be sustained by a control loop within the auditory system. One component of the control loop is the pitch-shift reflex (PSR). The PSR is a closed loop negative feedback reflex that is triggered in response to discrepancies between intended and perceived pitch with a latency of ~ 100 ms. Consecutive compensatory reflexive responses lead to oscillations in pitch every ~200 ms, resulting in ~5-Hz modulation of F0. Pitch-shift reflexes were elicited experimentally in six subjects while they sustained /u/ vowels at a comfortable pitch and loudness. Auditory feedback was sinusoidally modulated at discrete integer frequencies (1 to 10 Hz) with ±25 cents amplitude. Modulated auditory feedback induced oscillations in voice F0 output of all subjects at rates consistent with vocal vibrato and tremor. Transfer functions revealed peak gains at 4 to 7 Hz in all subjects, with an average peak gain at 5 Hz. These gains occurred in the modulation frequency region where the voice output and auditory feedback signals were in phase. A control loop in the auditory system may sustain vocal vibrato and tremorlike oscillations in voice F0. PMID:14514211

  16. The role of auditory feedback in sustaining vocal vibrato.

    PubMed

    Leydon, Ciara; Bauer, Jay J; Larson, Charles R

    2003-09-01

    Vocal vibrato and tremor are characterized by oscillations in voice fundamental frequency (F0). These oscillations may be sustained by a control loop within the auditory system. One component of the control loop is the pitch-shift reflex (PSR). The PSR is a closed loop negative feedback reflex that is triggered in response to discrepancies between intended and perceived pitch with a latency of approximately 100 ms. Consecutive compensatory reflexive responses lead to oscillations in pitch every approximately 200 ms, resulting in approximately 5-Hz modulation of F0. Pitch-shift reflexes were elicited experimentally in six subjects while they sustained /u/ vowels at a comfortable pitch and loudness. Auditory feedback was sinusoidally modulated at discrete integer frequencies (1 to 10 Hz) with +/- 25 cents amplitude. Modulated auditory feedback induced oscillations in voice F0 output of all subjects at rates consistent with vocal vibrato and tremor. Transfer functions revealed peak gains at 4 to 7 Hz in all subjects, with an average peak gain at 5 Hz. These gains occurred in the modulation frequency region where the voice output and auditory feedback signals were in phase. A control loop in the auditory system may sustain vocal vibrato and tremorlike oscillations in voice F0. PMID:14514211

  17. Using deflation in the pole assignment problem with output feedback

    NASA Technical Reports Server (NTRS)

    Miminis, George

    1989-01-01

    A direct algorithm is suggested for the computation of a linear output feedback for a multi input, multi output system such that the resultant closed-loop matrix has eigenvalues that include a specified set of eigenvalues. The algorithm uses deflation based on unitary similarity transformations. Thus researchers hope the algorithm is numerically stable; however, this has not been proven as yet.

  18. Neural cryptography with feedback.

    PubMed

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  19. COMPONENTS OF LASER SYSTEMS AND STABILITY PROBLEMS: Highly stable subpicosecond neodymium (Nd3+) glass laser with passive mode locking and negative feedback

    NASA Astrophysics Data System (ADS)

    Burneĭka, K.; Grigonis, R.; Piskarskas, A.; Sinkyavichyus, G.; Sirutkaĭtis, V.

    1988-08-01

    An electrically controlled feedback loop was used in a phosphate glass laser with passive mode locking to ensure stable generation of 500-600 fs pulses. This negative feedback loop ensured a high reproducibility of the energy and time characteristics of the pulses. The product of the spectral width of the pulses and their duration was 0.44.

  20. High voltage power supply

    NASA Technical Reports Server (NTRS)

    Ruitberg, A. P.; Young, K. M. (Inventor)

    1985-01-01

    A high voltage power supply is formed by three discrete circuits energized by a battery to provide a plurality of concurrent output signals floating at a high output voltage on the order of several tens of kilovolts. In the first two circuits, the regulator stages are pulse width modulated and include adjustable ressistances for varying the duty cycles of pulse trains provided to corresponding oscillator stages while the third regulator stage includes an adjustable resistance for varying the amplitude of a steady signal provided to a third oscillator stage. In the first circuit, the oscillator, formed by a constant current drive network and a tuned resonant network included a step up transformer, is coupled to a second step up transformer which, in turn, supplies an amplified sinusoidal signal to a parallel pair of complementary poled rectifying, voltage multiplier stages to generate the high output voltage.

  1. Imaging voltage in neurons

    PubMed Central

    Peterka, Darcy S.; Takahashi, Hiroto; Yuste, Rafael

    2011-01-01

    In the last decades, imaging membrane potential has become a fruitful approach to study neural circuits, especially in invertebrate preparations with large, resilient neurons. At the same time, particularly in mammalian preparations, voltage imaging methods suffer from poor signal to noise and secondary side effects, and they fall short of providing single-cell resolution when imaging of the activity of neuronal populations. As an introduction to these techniques, we briefly review different voltage imaging methods (including organic fluorophores, SHG chromophores, genetic indicators, hybrid, nanoparticles and intrinsic approaches), and illustrate some of their applications to neuronal biophysics and mammalian circuit analysis. We discuss their mechanisms of voltage sensitivity, from reorientation, electrochromic or electro-optical phenomena, to interaction among chromophores or membrane scattering, and highlight their advantages and shortcomings, commenting on the outlook for development of novel voltage imaging methods. PMID:21220095

  2. A Case Study of Representing Signal Transduction in Liver Cells as a Feedback Control Problem

    ERIC Educational Resources Information Center

    Singh, Abhay; Jayaraman, Arul; Hahn, Juergen

    2007-01-01

    Cell signaling pathways often contain feedback loops where proteins are produced that regulate signaling. While feedback regulatory mechanisms are commonly found in signaling pathways, there is no example available in the literature that is simple enough to be presented in an undergraduate control class. This paper presents a simulation study of…

  3. The Use of Feedback Mechanisms in Interpreting the Robustness of a Neoliberal Educational Assemblage

    ERIC Educational Resources Information Center

    Demerath, Peter; Mattheis, Allison

    2015-01-01

    This article demonstrates how using feedback mechanisms or "loops" as heuristic devices can help ethnographers explain the interior logic, robustness and contradictions within complex educational assemblages. After reviewing the use of feedback mechanisms in the natural and social sciences, particularly practice theory, the article…

  4. Feedback stabilization initiative

    SciTech Connect

    1997-06-01

    Much progress has been made in attaining high confinement regimes in magnetic confinement devices. These operating modes tend to be transient, however, due to the onset of MHD instabilities, and their stabilization is critical for improved performance at steady state. This report describes the Feedback Stabilization Initiative (FSI), a broad-based, multi-institutional effort to develop and implement methods for raising the achievable plasma betas through active MHD feedback stabilization. A key element in this proposed effort is the Feedback Stabilization Experiment (FSX), a medium-sized, national facility that would be specifically dedicated to demonstrating beta improvement in reactor relevant plasmas by using a variety of MHD feedback stabilization schemes.

  5. Thermal power loops

    NASA Technical Reports Server (NTRS)

    Gottschlich, Joseph M.; Richter, Robert

    1991-01-01

    The concept of a thermal power loop (TPL) to transport thermal power over relatively large distances is presented as an alternative to heat pipes and their derivatives. The TPL is compared to heat pipes, and capillary pumped loops with respect to size, weight, conservation of thermal potential, start-up, and 1-g testing capability. Test results from a proof of feasibility demonstrator at the NASA JPL are discussed. This analysis demonstrates that the development of specific thermal power loops will result in substantial weight and cost savings for many spacecraft.

  6. Multiprotein DNA Looping

    NASA Astrophysics Data System (ADS)

    Vilar, Jose M. G.; Saiz, Leonor

    2006-06-01

    DNA looping plays a fundamental role in a wide variety of biological processes, providing the backbone for long range interactions on DNA. Here we develop the first model for DNA looping by an arbitrarily large number of proteins and solve it analytically in the case of identical binding. We uncover a switchlike transition between looped and unlooped phases and identify the key parameters that control this transition. Our results establish the basis for the quantitative understanding of fundamental cellular processes like DNA recombination, gene silencing, and telomere maintenance.

  7. Engineering applications of a dynamical state feedback chaotification method

    NASA Astrophysics Data System (ADS)

    Şahin, Savaş; Güzeliş, Cüneyt

    2012-09-01

    This paper presents two engineering applications of a chaotification method which can be applied to any inputstate linearizable (nonlinear) system including linear controllable ones as special cases. In the used chaotification method, a reference chaotic and linear system can be combined into a special form by a dynamical state feedback increasing the order of the open loop system to have the same chaotic dynamics with the reference chaotic system. Promising dc motor applications of the method are implemented by the proposed dynamical state feedback which is based on matching the closed loop dynamics to the well known Chua and also Lorenz chaotic systems. The first application, which is the chaotified dc motor used for mixing a corn syrup added acid-base mixture, is implemented via a personal computer and a microcontroller based circuit. As a second application, a chaotified dc motor with a taco-generator used in the feedback is realized by using fully analog circuit elements.

  8. Control-structure interaction in precision pointing servo loops

    NASA Technical Reports Server (NTRS)

    Spanos, John T.

    1989-01-01

    The control-structure interaction problem is addressed via stability analysis of a generic linear servo loop model. With the plant described by the rigid body mode and a single elastic mode, structural flexibility is categorized into one of three types: (1) appendage, (2) in-the-loop minimum phase, and (3) in-the-loop nonminimum phase. Closing the loop with proportional-derivative (PD) control action and introducing sensor roll-off dynamics in the feedback path, stability conditions are obtained. Trade studies are conducted with modal frequency, modal participation, modal damping, loop bandwidth, and sensor bandwidth treated as free parameters. Results indicate that appendage modes are most likely to produce instability if they are near the sensor rolloff, whereas in-the-loop modes are most dangerous near the loop bandwidth. The main goal of this paper is to provide a fundamental understanding of the control-structure interaction problem so that it may benefit the design of complex spacecraft and pointing system servo loops. In this framework, the JPL Pathfinder gimbal pointer is considered as an example.

  9. Natively Unstructured Loops Differ from Other Loops

    PubMed Central

    Schlessinger, Avner; Liu, Jinfeng; Rost, Burkhard

    2007-01-01

    Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination. Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures. Here, we introduce an approach that uses a neural network in a very different and novel way. We hypothesize that very long contiguous segments with nonregular secondary structure (NORS regions) differ significantly from regular, well-structured loops, and that a method detecting such features could predict natively unstructured regions. Training our new method, NORSnet, on predicted information rather than on experimental data yielded three major advantages: it removed the overlap between testing and training, it systematically covered entire proteomes, and it explicitly focused on one particular aspect of unstructured regions with a simple structural interpretation, namely that they are loops. Our hypothesis was correct: well-structured and unstructured loops differ so substantially that NORSnet succeeded in their distinction. Benchmarks on previously used and new experimental data of unstructured regions revealed that NORSnet performed very well. Although it was not the best single prediction method, NORSnet was sufficiently accurate to flag unstructured regions in proteins that were previously not annotated. In one application, NORSnet revealed previously undetected unstructured regions in putative targets for structural genomics and may thereby contribute to increasing structural coverage of large eukaryotic families. NORSnet found unstructured regions more often in domain boundaries than expected at random. In another application, we estimated that 50%–70% of all worm proteins observed to have more than seven protein–protein interaction partners have unstructured regions. The comparative analysis between NORSnet and DISOPRED2 suggested that long

  10. Natively unstructured loops differ from other loops.

    PubMed

    Schlessinger, Avner; Liu, Jinfeng; Rost, Burkhard

    2007-07-01

    Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination. Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures. Here, we introduce an approach that uses a neural network in a very different and novel way. We hypothesize that very long contiguous segments with nonregular secondary structure (NORS regions) differ significantly from regular, well-structured loops, and that a method detecting such features could predict natively unstructured regions. Training our new method, NORSnet, on predicted information rather than on experimental data yielded three major advantages: it removed the overlap between testing and training, it systematically covered entire proteomes, and it explicitly focused on one particular aspect of unstructured regions with a simple structural interpretation, namely that they are loops. Our hypothesis was correct: well-structured and unstructured loops differ so substantially that NORSnet succeeded in their distinction. Benchmarks on previously used and new experimental data of unstructured regions revealed that NORSnet performed very well. Although it was not the best single prediction method, NORSnet was sufficiently accurate to flag unstructured regions in proteins that were previously not annotated. In one application, NORSnet revealed previously undetected unstructured regions in putative targets for structural genomics and may thereby contribute to increasing structural coverage of large eukaryotic families. NORSnet found unstructured regions more often in domain boundaries than expected at random. In another application, we estimated that 50%-70% of all worm proteins observed to have more than seven protein-protein interaction partners have unstructured regions. The comparative analysis between NORSnet and DISOPRED2 suggested that long

  11. Introduction to Loop Heat Pipes

    NASA Technical Reports Server (NTRS)

    Ku, Jentung

    2015-01-01

    This is the presentation file for the short course Introduction to Loop Heat Pipes, to be conducted at the 2015 Thermal Fluids and Analysis Workshop, August 3-7, 2015, Silver Spring, Maryland. This course will discuss operating principles and performance characteristics of a loop heat pipe. Topics include: 1) pressure profiles in the loop; 2) loop operating temperature; 3) operating temperature control; 4) loop startup; 4) loop shutdown; 5) loop transient behaviors; 6) sizing of loop components and determination of fluid inventory; 7) analytical modeling; 8) examples of flight applications; and 9) recent LHP developments.

  12. A low-power high-performance configurable auto-gain control loop for a digital hearing aid SoC

    NASA Astrophysics Data System (ADS)

    Chengying, Chen; Hainan, Liu; Yong, Hei; Jun, Fan; Xiaoyu, Hu

    2013-10-01

    A low-power, configurable auto-gain control loop for a digital hearing aid system on a chip (SoC) is presented. By adopting a mixed-signal feedback control structure and peak detection and judgment, it can work in automatic gain or variable gain control modes through a digital signal processing unit. A noise-reduction and dynamic range (DR) improvement technique is also used to ensure the DR of the circuit in a low-voltage supply. The circuit is implemented in an SMIC 0.13 μm 1P8M CMOS process. The measurement results show that in a 1 V power supply, 1.6 kHz input frequency and 200 mVp—p, the SFDR is 74.3 dB, the THD is 66.1 dB, and the total power is 89 μW, meeting the application requirements of hearing aid SoCs.

  13. High voltage pulse generator

    DOEpatents

    Fasching, George E.

    1977-03-08

    An improved high-voltage pulse generator has been provided which is especially useful in ultrasonic testing of rock core samples. An N number of capacitors are charged in parallel to V volts and at the proper instance are coupled in series to produce a high-voltage pulse of N times V volts. Rapid switching of the capacitors from the paralleled charging configuration to the series discharging configuration is accomplished by using silicon-controlled rectifiers which are chain self-triggered following the initial triggering of a first one of the rectifiers connected between the first and second of the plurality of charging capacitors. A timing and triggering circuit is provided to properly synchronize triggering pulses to the first SCR at a time when the charging voltage is not being applied to the parallel-connected charging capacitors. Alternate circuits are provided for controlling the application of the charging voltage from a charging circuit to be applied to the parallel capacitors which provides a selection of at least two different intervals in which the charging voltage is turned "off" to allow the SCR's connecting the capacitors in series to turn "off" before recharging begins. The high-voltage pulse-generating circuit including the N capacitors and corresponding SCR's which connect the capacitors in series when triggered "on" further includes diodes and series-connected inductors between the parallel-connected charging capacitors which allow sufficiently fast charging of the capacitors for a high pulse repetition rate and yet allow considerable control of the decay time of the high-voltage pulses from the pulse-generating circuit.

  14. Device for monitoring cell voltage

    DOEpatents

    Doepke, Matthias; Eisermann, Henning

    2012-08-21

    A device for monitoring a rechargeable battery having a number of electrically connected cells includes at least one current interruption switch for interrupting current flowing through at least one associated cell and a plurality of monitoring units for detecting cell voltage. Each monitoring unit is associated with a single cell and includes a reference voltage unit for producing a defined reference threshold voltage and a voltage comparison unit for comparing the reference threshold voltage with a partial cell voltage of the associated cell. The reference voltage unit is electrically supplied from the cell voltage of the associated cell. The voltage comparison unit is coupled to the at least one current interruption switch for interrupting the current of at least the current flowing through the associated cell, with a defined minimum difference between the reference threshold voltage and the partial cell voltage.

  15. Closed Loop Welding Controller for Manufacturing Process

    NASA Astrophysics Data System (ADS)

    Bonaccorso, F.; Bruno, C.; Cantelli, L.; Longo, D.; Muscato, G.; Rapisarda, S.

    2011-12-01

    The aim of this paper is to investigate on the closed loop welding controller of a rapid manufacturing Shaped Metal Deposition (SMD) process. SMD was developed and patented by Rolls-Royce in order to produce mechanical parts directly from a CAD model. A simplified SMD plant has been set up in order to investigate the welding dynamics and parameters and to develop a SMD automatic controller. On the basis of the experience acquired, some basic control laws have been developed, and a closed loop controller has been implemented. This controller permits to find and to maintain the process stability condition, so that the final process results totally automatic. The control is performed adjusting the welding conditions on the basis of arc voltage information obtained from the welding machine during the deposition. The experimental results reported confirm the validity of the proposed strategy.

  16. The Power of Feedback

    ERIC Educational Resources Information Center

    Hattie, John; Timperley, Helen

    2007-01-01

    Feedback is one of the most powerful influences on learning and achievement, but this impact can be either positive or negative. Its power is frequently mentioned in articles about learning and teaching, but surprisingly few recent studies have systematically investigated its meaning. This article provides a conceptual analysis of feedback and…

  17. Four perspectives on climate feedbacks

    NASA Astrophysics Data System (ADS)

    Feldl, N.; Roe, G. H.

    2013-08-01

    The spatial pattern of climate feedbacks depends on how the feedbacks are defined. We employ an idealized aquaplanet simulation with radiative kernels diagnosed for the precise model setup and characterize the meridional structure of feedbacks under four different definitions: local feedbacks, global feedbacks, nondimensional feedback factors, and relative humidity feedbacks. First, the spatial pattern of the reference response (i.e., the Planck feedback) is found to vary with definition, largely as a consequence of polar-amplified warming, which affects other high-latitude feedbacks as well. Second, locally defined feedbacks allow for decomposition of the surface temperature response as a function of feedbacks, forcing, and heat transport. Third, different insights into the dynamical and thermodynamical underpinnings of the subtropical moisture response are gained by comparing different versions of humidity feedbacks. Thus, alternative approaches to the conventional, global definition of feedbacks offer several advantages for understanding patterns of warming and, ultimately, regional climate predictability.

  18. A Review of Control Strategies in Closed-Loop Neuroprosthetic Systems.

    PubMed

    Wright, James; Macefield, Vaughan G; van Schaik, André; Tapson, Jonathan C

    2016-01-01

    It has been widely recognized that closed-loop neuroprosthetic systems achieve more favorable outcomes for users then equivalent open-loop devices. Improved performance of tasks, better usability, and greater embodiment have all been reported in systems utilizing some form of feedback. However, the interdisciplinary work on neuroprosthetic systems can lead to miscommunication due to similarities in well-established nomenclature in different fields. Here we present a review of control strategies in existing experimental, investigational and clinical neuroprosthetic systems in order to establish a baseline and promote a common understanding of different feedback modes and closed-loop controllers. The first section provides a brief discussion of feedback control and control theory. The second section reviews the control strategies of recent Brain Machine Interfaces, neuromodulatory implants, neuroprosthetic systems, and assistive neurorobotic devices. The final section examines the different approaches to feedback in current neuroprosthetic and neurorobotic systems. PMID:27462202

  19. A Review of Control Strategies in Closed-Loop Neuroprosthetic Systems

    PubMed Central

    Wright, James; Macefield, Vaughan G.; van Schaik, André; Tapson, Jonathan C.

    2016-01-01

    It has been widely recognized that closed-loop neuroprosthetic systems achieve more favorable outcomes for users then equivalent open-loop devices. Improved performance of tasks, better usability, and greater embodiment have all been reported in systems utilizing some form of feedback. However, the interdisciplinary work on neuroprosthetic systems can lead to miscommunication due to similarities in well-established nomenclature in different fields. Here we present a review of control strategies in existing experimental, investigational and clinical neuroprosthetic systems in order to establish a baseline and promote a common understanding of different feedback modes and closed-loop controllers. The first section provides a brief discussion of feedback control and control theory. The second section reviews the control strategies of recent Brain Machine Interfaces, neuromodulatory implants, neuroprosthetic systems, and assistive neurorobotic devices. The final section examines the different approaches to feedback in current neuroprosthetic and neurorobotic systems. PMID:27462202

  20. General, database-driven fast-feedback system for the Stanford Linear Collider

    SciTech Connect

    Rouse, F.; Allison, S.; Castillo, S.; Gromme, T.; Hall, B.; Hendrickson, L.; Himel, T.; Krauter, K.; Sass, B.' Shoaee, H.

    1991-05-01

    A new feedback system has been developed for stabilizing the SLC beams at many locations. The feedback loops are designed to sample and correct at the 60 Hz repetition rate of the accelerator. Each loop can be distributed across several of the standard 80386 microprocessors which control the SLC hardware. A new communications system, KISNet, has been implemented to pass signals between the microprocessors at this rate. The software is written in a general fashion using the state space formalism of digital control theory. This allows a new loop to be implemented by just setting up the online database and perhaps installing a communications link. 3 refs., 4 figs.

  1. Blind loop syndrome

    MedlinePlus

    ... operations for extreme obesity As a complication of inflammatory bowel disease Diseases such as diabetes or scleroderma may slow down movement in a segment of the intestine, leading to blind loop syndrome.

  2. Numerical Simulation of the Oscillations in a Mixer: An Internal Aeroacoustic Feedback System

    NASA Technical Reports Server (NTRS)

    Jorgenson, Philip C. E.; Loh, Ching Y.

    2004-01-01

    The space-time conservation element and solution element method is employed to numerically study the acoustic feedback system in a high temperature, high speed wind tunnel mixer. The computation captures the self-sustained feedback loop between reflecting Mach waves and the shear layer. This feedback loop results in violent instabilities that are suspected of causing damage to some tunnel components. The computed frequency is in good agreement with the available experimental data. The physical phenomena are explained based on the numerical results.

  3. Choking loops on surfaces.

    PubMed

    Feng, Xin; Tong, Yiying

    2013-08-01

    We present a method for computing "choking" loops--a set of surface loops that describe the narrowing of the volumes inside/outside of the surface and extend the notion of surface homology and homotopy loops. The intuition behind their definition is that a choking loop represents the region where an offset of the original surface would get pinched. Our generalized loops naturally include the usual 2g handles/tunnels computed based on the topology of the genus-g surface, but also include loops that identify chokepoints or bottlenecks, i.e., boundaries of small membranes separating the inside or outside volume of the surface into disconnected regions. Our definition is based on persistent homology theory, which gives a measure to topological structures, thus providing resilience to noise and a well-defined way to determine topological feature size. More precisely, the persistence computed here is based on the lower star filtration of the interior or exterior 3D domain with the distance field to the surface being the associated 3D Morse function. PMID:23744260

  4. Feedback control laws for highly maneuverable aircraft

    NASA Technical Reports Server (NTRS)

    Garrard, William L.; Balas, Gary J.

    1992-01-01

    The results of a study of the application of H infinity and mu synthesis techniques to the design of feedback control laws for the longitudinal dynamics of the High Angle of Attack Research Vehicle (HARV) are presented. The objective of this study is to develop methods for the design of feedback control laws which cause the closed loop longitudinal dynamics of the HARV to meet handling quality specifications over the entire flight envelope. Control law designs are based on models of the HARV linearized at various flight conditions. The control laws are evaluated by both linear and nonlinear simulations of typical maneuvers. The fixed gain control laws resulting from both the H infinity and mu synthesis techniques result in excellent performance even when the aircraft performs maneuvers in which the system states vary significantly from their equilibrium design values. Both the H infinity and mu synthesis control laws result in performance which compares favorably with an existing baseline longitudinal control law.

  5. Nonlinear dynamics of neural delayed feedback

    SciTech Connect

    Longtin, A.

    1990-01-01

    Neural delayed feedback is a property shared by many circuits in the central and peripheral nervous systems. The evolution of the neural activity in these circuits depends on their present state as well as on their past states, due to finite propagation time of neural activity along the feedback loop. These systems are often seen to undergo a change from a quiescent state characterized by low level fluctuations to an oscillatory state. We discuss the problem of analyzing this transition using techniques from nonlinear dynamics and stochastic processes. Our main goal is to characterize the nonlinearities which enable autonomous oscillations to occur and to uncover the properties of the noise sources these circuits interact with. The concepts are illustrated on the human pupil light reflex (PLR) which has been studied both theoretically and experimentally using this approach. 5 refs., 3 figs.

  6. Pole placement with constant gain output feedback

    NASA Technical Reports Server (NTRS)

    Sridhar, B.; Lindorff, D. P.

    1972-01-01

    Given a linear time invariant multivariable system with m inputs and p outputs, it was shown that p closed loop poles of the system can be preassigned arbitrarily using constant gain output feedback provided (A circumflex, B circumflex) is controllable. These data show that if (A circumflex, B circumflex, C circumflex) is controllable and observable, and Rank B circumflex = m, Rank C circumflex = p, then max (m,p) poles of the system can be assigned arbitarily using constant gain output feedback. Further, it is shown that in some cases more than max (m,p) poles can be arbitrarily assigned. A least square design technique is outlined to approximate the desired pole locations when it is not possible to place all the poles.

  7. Tissue modification with feedback: the smart scalpel

    NASA Astrophysics Data System (ADS)

    Sebern, Elizabeth L.; Brenan, Colin J. H.; Anderson, R. Rox; Hunter, Ian W.

    1998-10-01

    While feedback control is widespread throughout many engineering fields, there are almost no examples of surgical instruments that utilize a real-time detection and intervention strategy. This concept of closed loop feedback can be applied to the development of autonomous or semi- autonomous minimally invasive robotic surgical systems for efficient excision or modification of diseased tissue. Spatially localized regions of the tissue are first probed to distinguish pathological from healthy tissue based on differences in histochemical and morphological properties. Energy is directed to only the diseased tissue, minimizing collateral damage by leaving the adjacent healthy tissue intact. Continuous monitoring determines treatment effectiveness and, if needed, enables real-time treatment modifications to produce optimal therapeutic outcomes. The present embodiment of this general concept is a microsurgical instrument we call the Smart Scalpel, designed to treat skin angiodysplasias such as port wine stains. Other potential Smart Scalpel applications include psoriasis treatment and early skin cancer detection and intervention.

  8. Dynamic biomaterials: toward engineering autonomous feedback.

    PubMed

    Morris, Eliza; Chavez, Michael; Tan, Cheemeng

    2016-06-01

    Dynamic biomaterials are biocompatible engineered systems capable of sensing and actively responding to their surrounding environment. They are of growing interest, both as models in basic research to understand complex cellular systems and in medical applications. Here, we review recent advances in nano-scale and micro-scale biomaterials, specifically artificial cells consisting of compartmentalized biochemical reactions and biologically compatible hydrogels. These dynamic biomaterials respond to stimuli through triggered reactions, reaction cascades, logic gates, and autonomous feedback loops. We outline the advances and remaining challenges in implementing such 'smart' biomaterials capable of autonomously responding to environmental stimuli. PMID:26974245

  9. Voltage controlled current source

    DOEpatents

    Casne, Gregory M.

    1992-01-01

    A seven decade, voltage controlled current source is described for use in testing intermediate range nuclear instruments that covers the entire test current range of from 10 picoamperes to 100 microamperes. High accuracy is obtained throughout the entire seven decades of output current with circuitry that includes a coordinated switching scheme responsive to the input signal from a hybrid computer to control the input voltage to an antilog amplifier, and to selectively connect a resistance to the antilog amplifier output to provide a continuous output current source as a function of a preset range of input voltage. An operator controlled switch provides current adjustment for operation in either a real-time simulation test mode or a time response test mode.

  10. Electron launching voltage monitor

    DOEpatents

    Mendel, Clifford W.; Savage, Mark E.

    1992-01-01

    An electron launching voltage monitor measures MITL voltage using a relationship between anode electric field and electron current launched from a cathode-mounted perturbation. An electron launching probe extends through and is spaced from the edge of an opening in a first MITL conductor, one end of the launching probe being in the gap between the MITL conductor, the other end being adjacent a first side of the first conductor away from the second conductor. A housing surrounds the launching probe and electrically connects the first side of the first conductor to the other end of the launching probe. A detector detects the current passing through the housing to the launching probe, the detected current being representative of the voltage between the conductors.

  11. Electron launching voltage monitor

    DOEpatents

    Mendel, C.W.; Savage, M.E.

    1992-03-17

    An electron launching voltage monitor measures MITL voltage using a relationship between anode electric field and electron current launched from a cathode-mounted perturbation. An electron launching probe extends through and is spaced from the edge of an opening in a first MITL conductor, one end of the launching probe being in the gap between the MITL conductor, the other end being adjacent a first side of the first conductor away from the second conductor. A housing surrounds the launching probe and electrically connects the first side of the first conductor to the other end of the launching probe. A detector detects the current passing through the housing to the launching probe, the detected current being representative of the voltage between the conductors. 5 figs.

  12. High voltage variable diameter insulator

    DOEpatents

    Vanacek, D.L.; Pike, C.D.

    1982-07-13

    A high voltage feedthrough assembly having a tubular insulator extending between the ground plane ring and the high voltage ring. The insulator is made of Pyrex and decreases in diameter from the ground plane ring to the high voltage ring, producing equipotential lines almost perpendicular to the wall of the insulator to optimize the voltage-holding capability of the feedthrough assembly.

  13. Voltage Regulators for Photovoltaic Systems

    NASA Technical Reports Server (NTRS)

    Delombard, R.

    1986-01-01

    Two simple circuits developed to provide voltage regulation for highvoltage (i.e., is greater than 75 volts) and low-voltage (i.e., is less than 36 volts) photovoltaic/battery power systems. Use of these circuits results in voltage regulator small, low-cost, and reliable, with very low power dissipation. Simple oscillator circuit controls photovoltaic-array current to regulate system voltage and control battery charging. Circuit senses battery (and system) voltage and adjusts array current to keep battery voltage from exceeding maximum voltage.

  14. Feedback in distance education.

    PubMed

    Hudspeth, D

    1988-01-01

    Some tips, strategies, and techniques are presented for incorporating learner feedback into distance education courses. The most common form of learner feedback is immediate Knowledge of Response (KR). This general term can be delineated further as either Knowledge of Correct Response (KCR) or Knowledge of Incorrect Response (KIR). KCR is most useful for learning tasks that require a high level of automatic response such as vocabulary development and naming chemical structures. It also can be used for higher levels of learning. KIR occurs when the learner makes a response and knows only whether the response was correct or incorrect. If the learner was incorrect, the correct answer is not provided. Distant learners, as well as learners in a typical classroom, benefit from positive feedback, e.g., a few words written on the side of an assignment or a short note of encouragement. Personalized feedback tells students if they are performing satisfactorily and, if provided early in a course, can help reduce student attrition. If immediate feedback after an examination cannot be provided, every effort should be made to score and return the test as soon as possible before the student is expected to begin study on subsequent lessons. If this is not possible, a test review sheet could be mailed back upon receipt of the examination. Microcomputers are devices that can provide rapid and useful feedback, yet many methods that do not rely on computers can provide feedback. These include practice tests, small group exercises, and checklist response sheets. In addition to formally providing feedback after an assignment or examination, it is possible to use the principles of feedback by embedding questions and answers in text, audio, or video materials.

  15. Small-signal, continuous, exact model of PWM voltage regulators

    NASA Astrophysics Data System (ADS)

    Burkhardt, W.; Maranesi, P.; Varoli, V.

    1985-02-01

    The small-signal time-continuous open-loop response of buck, boost, and buck-boost pulse-width-modulation (PWM) voltage regulators using MOSFET switches in their power stages is modeled, applying a time-domain sampling theorem (Woodward, 1953) to obtain the Fourier open-loop transfer function corresponding to the comb function describing the response at the chopping instants only. The results are presented graphically along with simplified circuit diagrams of the PWM devices, and the accuracy and computational efficiency of the analytical approach are indicated.

  16. High Voltage Insulation Technology

    NASA Astrophysics Data System (ADS)

    Scherb, V.; Rogalla, K.; Gollor, M.

    2008-09-01

    In preparation of new Electronic Power Conditioners (EPC's) for Travelling Wave Tub Amplifiers (TWTA's) on telecom satellites a study for the development of new high voltage insulation technology is performed. The initiative is mandatory to allow compact designs and to enable higher operating voltages. In a first task a market analysis was performed, comparing different materials with respect to their properties and processes. A hierarchy of selection criteria was established and finally five material candidates (4 Epoxy resins and 1 Polyurethane resin) were selected to be further investigated in the test program. Samples for the test program were designed to represent core elements of an EPC, the high voltage transformer and Printed Circuit Boards of the high voltage section. All five materials were assessed in the practical work flow of the potting process and electrical, mechanical, thermal and lifetime testing was performed. Although the lifetime tests results were overlayed by a larges scatter, finally two candidates have been identified for use in a subsequent qualification program. This activity forms part of element 5 of the ESA ARTES Programme.

  17. Geomagnetism and Induced Voltage

    ERIC Educational Resources Information Center

    Abdul-Razzaq, W.; Biller, R. D.

    2010-01-01

    Introductory physics laboratories have seen an influx of "conceptual integrated science" over time in their classrooms with elements of other sciences such as chemistry, biology, Earth science, and astronomy. We describe a laboratory to introduce this development, as it attracts attention to the voltage induced in the human brain as it is…

  18. Measuring Breakdown Voltage.

    ERIC Educational Resources Information Center

    Auer, Herbert J.

    1978-01-01

    The article discusses an aspect of conductivity, one of the electrical properties subdivisions, and describes a tester that can be shop-built. Breakdown voltage of an insulation material is specifically examined. Test procedures, parts lists, diagrams, and test data form are included. (MF)

  19. Applications of phase-locking loops to synchronization problems in space communications links

    NASA Astrophysics Data System (ADS)

    Maral, G.; Bousquet, M.

    1981-12-01

    Components and methods of assuring the synchronization of carriers and bits in space communications where the signal to noise ratios are low are presented. Closed loop systems are described which function by phase estimation through satisfaction of maximum likelihood criteria. Applications are discussed for a loop type carrier with feedback decision, a Costas loop and an x-squared nonlinear synchronizer, and early/late gate synchronizers. Additional consideration is given to data transition tracking loops and nonlinear synchronizers, where a nonlinear algorithm filter processes the signal in the baseband. Future implementation of microprocessors for entirely numerical synchronization is indicated.

  20. Laser Doppler vibrometer employing active frequency feedback.

    PubMed

    Chijioke, Akobuije; Lawall, John

    2008-09-20

    We present a heterodyne Michelson interferometer for vibration measurement in which feedback is used to obviate the need to unwrap phase data. The Doppler shift of a vibrating target mirror is sensed interferometrically and compensated by means of a voltage-controlled oscillator driving an acousto-optic modulator. For frequencies within the servo bandwidth, the oscillator control voltage provides a direct measurement of the target velocity. Outside the servo bandwidth, phase-sensitive detection is used to evaluate high-frequency displacements. This approach is of great interest for the frequently-occurring situation where vibration amplitudes at low frequency exceed an optical wavelength, but knowledge of the vibration spectrum at high frequency is important as well.