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Sample records for acoustic feedback loop

  1. Smart feedback loops

    NASA Astrophysics Data System (ADS)

    Chepurnov, A. S.; Gribov, I. V.; Gudkov, K. A.; Shumakov, A. V.; Shvedunov, V. I.

    1994-12-01

    It is necessary to find the golden mean in allocating the processing resources of a computer control system. Traditionally, feedback loops operate at the lower levels to ensure safe and stable operation of the accelerator. At present we use analogue and digital feedback loops. Some systems, such as the RF, require more complex algorithms. A possible way of providing these, using digital signal processors is described. The results of tests with the Race-Track Microtron Linac are given and the sources of the main internal and external disturbances have been analysed.

  2. Role of the geodesic acoustic mode shearing feedback loop in transport bifurcations and turbulence spreading

    SciTech Connect

    Miki, K.; Diamond, P. H.

    2010-03-15

    A theory of the effect of the geodesic acoustic mode (GAM) on turbulence is presented. Two synergistic issues are elucidated: namely, the physics of the zonal flow modulation and its role in the L-H transition, and the role of the GAM wave group propagation in turbulence spreading. Using a wavekinetic modulational analysis, the response of the turbulence intensity field to the GAM is calculated. This analysis differs from previous studies of zero-frequency zonal flows since it accounts for resonance between the drift wave group speed and the GAM strain field, which induces secularity. This mechanism is referred to as secular stochastic shearing. Finite real frequency and radial group velocity are intrinsic to the GAM, so its propagation can induce nonlocal phenomena at the edge and pedestal regions. To understand the effect of the GAM on turbulence and transition dynamics, a predator-prey model incorporating the dynamics of both turbulence and the GAMs is constructed and analyzed for stability around fixed points. Three possible states are identified, namely, an L-modelike stationary state, a reduced turbulence state, and a GAM limit-cycle state. The system is attracted to the state with the minimum turbulence level.

  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. The application of smart structures toward feedback suppression in amplified acoustic guitars

    NASA Astrophysics Data System (ADS)

    Griffin, Steve; Lane, Steven A.; Clark, Robert L.

    2003-06-01

    Smart structures technology can be applied to amplified acoustic guitars to prevent instability resulting from acoustic feedback. This work presents a coupled model of the guitar dynamics and the acoustic feedback mechanism, and explains how a simple control loop using a piezoelectric ceramic actuator can be used to reduce the effects of acoustic feedback. In addition to model simulations, experimental results using a real system and a simple controller are presented. The results show that a significantly higher (7 dB) guitar output can be achieved before instability, without detrimentally affecting the amplified and unamplified guitar response.

  5. Are feedback loops destructive to synchronization?

    NASA Astrophysics Data System (ADS)

    Sheshbolouki, A.; Zarei, M.; Sarbazi-Azad, H.

    2015-08-01

    We study the effects of directionality on synchronization of dynamical networks. Performing the linear stability analysis and the numerical simulation of the Kuramoto model in directed networks, we show that balancing in- and out-degrees of all nodes enhances the synchronization of sparse networks, especially in networks with high clustering coefficient and homogeneous degree distribution. Furthermore, by omitting all the feedback loops, we show that while hierarchical directed acyclic graphs are structurally highly synchronizable, their global synchronization is too sensitive to the choice of natural frequencies and is strongly affected by noise.

  6. 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

  7. Application of acoustic feedback to target detection in a waveguide: experimental demonstration at the ultrasonic scale.

    PubMed

    Roux, Philippe; Marandet, Christian; La Rizza, Patrick; Kuperman, W A

    2011-07-01

    People are familiar with the acoustic feedback phenomenon, which results in a loud sound that is heard when a musician plays an electric instrument directly into a speaker. Acoustic feedback occurs when a source and a receiver are connected both acoustically through the propagation medium and electrically through an amplifier, such that the amplified received signal is continuously re-emitted by the source. The acoustic feedback can be initiated from a continuous sine wave. When the emitter and the receiver are in phase, resonance is obtained, which appears to be highly sensitive to any fluctuation of the propagation medium. Another procedure consists in initiating the acoustic feedback from a continuous loop of ambient noise. It then generates an unstable self-sustained feedback oscillator (SFO) that is tested here as a method for monitoring temperature fluctuations of a shallow-water oceanic environment. The goal of the present study is to reproduce and study the SFO at the laboratory scale in an ultrasonic waveguide. The experimental results demonstrate the potential applications of the SFO for the detection of a target in the framework of the acoustic-barrier problem in shallow-water acoustics.

  8. Digital Phase-Locked Loop With Phase And Frequency Feedback

    NASA Technical Reports Server (NTRS)

    Thomas, J. Brooks

    1991-01-01

    Advanced design for digital phase-lock loop (DPLL) allows loop gains higher than those used in other designs. Divided into two major components: counterrotation processor and tracking processor. Notable features include use of both phase and rate-of-change-of-phase feedback instead of frequency feedback alone, normalized sine phase extractor, improved method for extracting measured phase, and improved method for "compressing" output rate.

  9. Decision feedback loop for tracking a polyphase modulated carrier

    NASA Technical Reports Server (NTRS)

    Simon, M. K. (Inventor)

    1974-01-01

    A multiple phase modulated carrier tracking loop for use in a frequency shift keying system is described in which carrier tracking efficiency is improved by making use of the decision signals made on the data phase transmitted in each T-second interval. The decision signal is used to produce a pair of decision-feedback quadrature signals for enhancing the loop's performance in developing a loop phase error signal.

  10. Reciprocal Feedback: Closing the Loop on Postactivity Surveys.

    PubMed

    Watson, Richard A

    2015-01-01

    Those who conduct feedback surveys, which follow almost every CME presentation and medical-school lecture, would do well to offer participants' reciprocal feedback. That is, the course director should provide each survey respondent, on request, a brief summary of the comments received from this survey and the extent to which the recommendations will lead to objective improvements in the future. Surveyors who provide respondents with reciprocal feedback can expect heightened credibility, more reliable feedback in the future, and an added incentive to effect significant change for the better. Feedback has not circled all the way back until we have provided a succinct summary of results to those who have offered us their comments and suggestions. Let us close the loop; let reciprocal feedback become the last word in CME surveys.

  11. Imaging of acoustic fields using optical feedback interferometry.

    PubMed

    Bertling, Karl; Perchoux, Julien; Taimre, Thomas; Malkin, Robert; Robert, Daniel; Rakić, Aleksandar D; Bosch, Thierry

    2014-12-01

    This study introduces optical feedback interferometry as a simple and effective technique for the two-dimensional visualisation of acoustic fields. We present imaging results for several pressure distributions including those for progressive waves, standing waves, as well as the diffraction and interference patterns of the acoustic waves. The proposed solution has the distinct advantage of extreme optical simplicity and robustness thus opening the way to a low cost acoustic field imaging system based on mass produced laser diodes.

  12. 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.

  13. Suppression of Spontaneous Gas Oscillations by Acoustic Self-Feedback

    NASA Astrophysics Data System (ADS)

    Biwa, Tetsushi; Sawada, Yoshiki; Hyodo, Hiroaki; Kato, Soichiro

    2016-10-01

    This paper demonstrates a method of acoustical self-feedback to suppress spontaneous gas oscillations such as those observed in combustors of gas-turbine engines. Whereas a conventional feedback system consists of electromechanical devices, the present method achieves acoustical self-feedback with a hollow tube that connects two positions of the oscillation system. A model oscillator of combustion-driven gas oscillations is designed and built to demonstrate the applicability of the self-feedback concept. Stability analysis through measurements of Q values (quality factor) of oscillations shows that the desired delay time and gain are obtained when the tube length is equal to the odd integer times half the wavelength of the anticipated acoustic oscillations.

  14. 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.

  15. Speaker compensation for local perturbation of fricative acoustic feedback.

    PubMed

    Casserly, Elizabeth D

    2011-04-01

    Feedback perturbation studies of speech acoustics have revealed a great deal about how speakers monitor and control their productions of segmental (e.g., formant frequencies) and non-segmental (e.g., pitch) linguistic elements. The majority of previous work, however, overlooks the role of acoustic feedback in consonant production and makes use of acoustic manipulations that effect either entire utterances or the entire acoustic signal, rather than more temporally and phonetically restricted alterations. This study, therefore, seeks to expand the feedback perturbation literature by examining perturbation of consonant acoustics that is applied in a time-restricted and phonetically specific manner. The spectral center of the alveopalatal fricative [∫] produced in vowel-fricative-vowel nonwords was incrementally raised until it reached the potential for [s]-like frequencies, but the characteristics of high-frequency energy outside the target fricative remained unaltered. An "offline," more widely accessible signal processing method was developed to perform this manipulation. The local feedback perturbation resulted in changes to speakers' fricative production that were more variable, idiosyncratic, and restricted than the compensation seen in more global acoustic manipulations reported in the literature. Implications and interpretations of the results, as well as future directions for research based on the findings, are discussed.

  16. Active vibroacoustic control with multiple local feedback loops.

    PubMed

    Elliott, Stephen J; Gardonio, Paolo; Sors, Thomas C; Brennan, Michael J

    2002-02-01

    When multiple actuators and sensors are used to control the vibration of a panel, or its sound radiation, they are usually positioned so that they couple into specific modes and are all connected together with a centralized control system. This paper investigates the physical effects of having a regular array of actuator and sensor pairs that are connected only by local feedback loops. An array of 4 x 4 force actuators and velocity sensors is first simulated, for which such a decentralized controller can be shown to be unconditionally stable. Significant reductions in both the kinetic energy of the panel and in its radiated sound power can be obtained for an optimal value of feedback gain, although higher values of feedback gain can induce extra resonances in the system and degrade the performance. A more practical transducer pair, consisting of a piezoelectric actuator and velocity sensor, is also investigated and the simulations suggest that a decentralized controller with this arrangement is also stable over a wide range of feedback gains. The resulting reductions in kinetic energy and sound power are not as great as with the force actuators, due to the extra resonances being more prominent and at lower frequencies, but are still worthwhile. This suggests that an array of independent modular systems, each of which included an actuator, a sensor, and a local feedback control loop, could be a simple and robust method of controlling broadband sound transmission when integrated into a panel.

  17. Feedback Loops of the Mammalian Circadian Clock Constitute Repressilator

    PubMed Central

    Pett, J. Patrick; Korenčič, Anja; Wesener, Felix; Kramer, Achim; Herzel, Hanspeter

    2016-01-01

    Mammals evolved an endogenous timing system to coordinate their physiology and behaviour to the 24h period of the solar day. While it is well accepted that circadian rhythms are generated by intracellular transcriptional feedback loops, it is still debated which network motifs are necessary and sufficient for generating self-sustained oscillations. Here, we systematically explore a data-based circadian oscillator model with multiple negative and positive feedback loops and identify a series of three subsequent inhibitions known as “repressilator” as a core element of the mammalian circadian oscillator. The central role of the repressilator motif is consistent with time-resolved ChIP-seq experiments of circadian clock transcription factors and loss of rhythmicity in core clock gene knockouts. PMID:27942033

  18. System and method of designing models in a feedback loop

    DOEpatents

    Gosink, Luke C.; Pulsipher, Trenton C.; Sego, Landon H.

    2017-02-14

    A method and system for designing models is disclosed. The method includes selecting a plurality of models for modeling a common event of interest. The method further includes aggregating the results of the models and analyzing each model compared to the aggregate result to obtain comparative information. The method also includes providing the information back to the plurality of models to design more accurate models through a feedback loop.

  19. Closed-Loop Acoustic Control of Reverberant Room for Satellite Environmental Testing

    NASA Astrophysics Data System (ADS)

    Janssens, Karl; Bianciardi, Fabio; Sabbatini, Danilo; Debille, Jan; Carrella, Alex

    2012-07-01

    The full satellite acoustic test is an important milestone in a satellite launch survivability verification campaign. This test is required to verify the satellite’s mechanical design against the high-level acoustic loads induced by the launch vehicle during the atmospheric flight. During the test, the satellite is subjected to a broadband diffuse acoustic field, reproducing the pressure levels observed during launch. The excitation is in most cases provided by a combination of horns for the low frequencies and noise generators for the higher frequencies. Acoustic control tests are commonly performed in reverberant rooms, controlling the sound pressure levels in third octave bands over the specified target spectrum. This paper discusses an automatic feedback control system for acoustic control of large reverberation rooms for satellite environmental testing. The acoustic control system consists of parallel third octave PI (Proportional Integral) feedback controllers that take the reverberation characteristics of the room into consideration. The drive output of the control system is shaped at every control step based on the comparison of the average third octave noise spectrum, measured from a number of microphones in the test room, with the target spectrum. Cross-over filters split the output drive into band- limited signals to feed each of the horns. The control system is realized in several steps. In the first phase, a dynamic process model is developed, including the non-linear characteristics of the horns and the reverberant properties of the room. The model is identified from dynamic experiments using system identification techniques. In the next phase, an adequate control strategy is designed which is capable of reaching the target spectrum in the required time period without overshoots. This control strategy is obtained from model-in-the-loop (MIL) simulations, evaluating the performance of various potential strategies. Finally, the proposed strategy is

  20. The Effect of Negative Feedback Loops on the Dynamics of Boolean Networks

    PubMed Central

    Sontag, Eduardo; Veliz-Cuba, Alan; Laubenbacher, Reinhard; Jarrah, Abdul Salam

    2008-01-01

    Feedback loops play an important role in determining the dynamics of biological networks. To study the role of negative feedback loops, this article introduces the notion of distance-to-positive-feedback which, in essence, captures the number of independent negative feedback loops in the network, a property inherent in the network topology. Through a computational study using Boolean networks, it is shown that distance-to-positive-feedback has a strong influence on network dynamics and correlates very well with the number and length of limit cycles in the phase space of the network. To be precise, it is shown that, as the number of independent negative feedback loops increases, the number (length) of limit cycles tends to decrease (increase). These conclusions are consistent with the fact that certain natural biological networks exhibit generally regular behavior and have fewer negative feedback loops than randomized networks with the same number of nodes and same connectivity. PMID:18375509

  1. 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

  2. Silicon photonic dynamic optical channel leveler with external feedback loop.

    PubMed

    Doylend, J K; Jessop, P E; Knights, A P

    2010-06-21

    We demonstrate a dynamic optical channel leveler composed of a variable optical attenuator (VOA) integrated monolithically with a defect-mediated photodiode in a silicon photonic waveguide device. An external feedback loop mimics an analog circuit such that the photodiode directly controls the VOA to provide blind channel leveling within +/-1 dB across a 7-10 dB dynamic range for wavelengths from 1530 nm to 1570 nm. The device consumes approximately 50 mW electrical power and occupies a 6 mm x 0.1 mm footprint per channel. Dynamic leveling is accomplished without tapping optical power from the output path to the photodiode and thus the loss penalty is minimized.

  3. 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.

  4. 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

  5. Real-time RNN-based acoustic thermometry with feedback control

    NASA Astrophysics Data System (ADS)

    Hsu, Stephen J.; Nam, Joana H.; Fan, Liexiang; Brunke, Shelby S.; Sekins, K. Michael

    2017-03-01

    A major obstacle to the widespread adoption of HIFU therapy is the development of a suitable method of monitoring the a blation therapy in real-time. While MR-thermometry has emerged as a promising method for HIFU therapy monitoring, acoustic guidance has continuously been sought for reasons of cost and practicality. We have previously demonstrated the potential of acoustic thermometry, by using a recurrent neural network (RNN) to estimate changes in tissue temperature during HIFU ablation therapies. A limitation of this method is that an excessive therapeutic dose can cause multiple, non-linear changes within the ultrasound data, resulting in unreliable temperature estimates from the RNN. Accordingly, we propose a revised method of dosing wherein closed loop feedback is used to provide a controlled and specific dose; not only to ensure an efficacious lesion, but also to preserve the integrity of the ultrasound image, thereby producing accurate temperature estimates from the RNN. This investigation of controlling the thermal dose using feedback was performed on ex vivo bovine liver. The acoustic parameters used as inputs to the RNN were: changes in integrated backscatter intensity, thermal strain, and decorrelation. The therapeutic dose was delivered using a 1.1 MHz, 2D-array HIFU transducer transmitting at regular intervals during a 40-second dose. Interleaved between these regular HIFU dose intervals, volumetric ultrasound images were acquired on a Siemens ACUSON SC2000, with a 4Zlc probe. Feedback was introduced to the system by varying the HIFU duty cycle, in order to minimize the difference between a desired temperature curve (assigned a priori) and the estimated focal temperature values. Two methods were used for obtaining the focal temperature: the first was direct measurement using a 75-micron copper-constantan thermocouple embedded within the liver sample, and the second was temperature estimation as calculated from the RNN-based output temperatures

  6. 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)…

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

    NASA Astrophysics Data System (ADS)

    Huang, G.; Byrd, J. M.

    2006-11-01

    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.

  8. Design of PID controllers in double feedback loops for SISO systems with set-point filters.

    PubMed

    Vijayan, V; Panda, Rames C

    2012-07-01

    A PID controller is widely used to control industrial processes that are mostly open loop stable or unstable. Selection of proper feedback structure and controller tuning helps to improve the performance of the loop. In this paper a double-feedback loop/method is used to achieve stability and better performance of the process. The internal feedback is used for stabilizing the process and the outer loop is used for good setpoint tracking. An internal model controller (IMC) based PID method is used for tuning the outer loop controller. Autotuning based on relay feedback or the Ziegler-Nichols method can be used for tuning an inner loop controller. A tuning parameter (λ) that is used to tune IMC-PID is used as a time constant of a setpoint filter that is used for reducing the peak overshoot. The method has been tested successfully on many low order processes.

  9. Investigation of a Phase-Locked Loop Receiver for a Parametric Acoustic Receiving Array.

    DTIC Science & Technology

    1980-05-05

    KEY WORDS (Continue on reverse side if necesary and Identify by block number, PARRAY Nonlinear Acoustics Parametric Reception Phase-Locked Loop...loop (PLL) demodulator considered for use with the parametric acoustic receiving array ( PARRAY ). The PARRAY as an acoustic sensor is explained and the...effects of longitudinal transducer motion on the PARRAY are described. This transducer vibration produces intermodulation products between the desired

  10. Multivariable feedback active structural acoustic control using adaptive piezoelectric sensoriactuators.

    PubMed

    Vipperman, J S; Clark, R L

    1999-01-01

    An experimental implementation of a multivariable feedback active structural acoustic control system is demonstrated on a piezostructure plate with pinned boundary conditions. Four adaptive piezoelectric sensoriactuators provide an array of truly colocated actuator/sensor pairs to be used as control transducers. Radiation filters are developed based on the self- and mutual-radiation efficiencies of the structure and are included into the performance cost of an H2 control law which minimizes total radiated sound power. In the cost function, control effort is balanced with reductions in radiated sound power. A similarity transform which produces generalized velocity states that are required as inputs to the radiation filters is presented. Up to 15 dB of attenuation in radiated sound power was observed at the resonant frequencies of the piezostructure.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Acoustic signature reduction using feedback of piezoelectric layers

    NASA Astrophysics Data System (ADS)

    Hamberg, Johan; Malmgren, Anders

    2000-06-01

    The possibilities of using dynamic feedback of piezoelectric layers for controlling the acoustic properties of a surface are investigated. The investigation shows that in principle it is possible to achieve desired properties (e.g. no reflection, artificial transparency or simultaneous transmission and reception of information) using a single piezo-electric layer. The layer then operates both as a sensor and as an actuator. This approach can be described as controlling the boundary conditions of the acoustic field. The study shows that this will work well, also in practice, if the material has an electromechanic coupling factor that is large enough. Explicit controllers for these cases are given. However, for the values of electro-mechanic coupling factors of available materials, the above construction is not suitable for practical purposes, due to non-robustness. Therefore, the possibility of using multiple layers is also investigated. It turns out that a two layer construction can achieve the properties of a single layer with large electro-mechanic coupling factor. For the specific problem of achieving no reflection, an explicit construction of a realistic controller is given. Requirements of robust stability and limited voltage amplitudes imply that low reflection cannot be achieved at low and high frequencies. However for a large frequency interval, it is possible to obtain low reflection. It is shown that both the gain and phase margins are infinite with this controller. Our work makes extensive use of the Redheffer star-product for systematic modeling, analysis and synthesis of the system and the regulator.

  16. Reverse quantum state engineering using electronic feedback loops

    NASA Astrophysics Data System (ADS)

    Kießlich, Gerold; Emary, Clive; Schaller, Gernot; Brandes, Tobias

    2012-12-01

    We propose an all-electronic technique to manipulate and control interacting quantum systems by unitary single-jump feedback conditioned on the outcome of a capacitively coupled electrometer and, in particular, a single-electron transistor. We provide a general scheme for stabilizing pure states in the quantum system and use an effective Hamiltonian method for the quantum master equation to elaborate on the nature of stabilizable states and the conditions under which state purification can be achieved. The state engineering within the quantum feedback scheme is shown to be linked with the solution of an inverse eigenvalue problem. Two applications of the feedback scheme are presented in detail: (i) stabilization of delocalized pure states in a single charge qubit and (ii) entanglement stabilization in two coupled charge qubits. In the latter example, we demonstrate the stabilization of a maximally entangled Bell state for certain detector positions and local feedback operations.

  17. Acoustic emission feedback control for control of boiling in a microwave oven

    SciTech Connect

    White, T.L.

    1991-02-26

    This patent describes an acoustic emission based feedback system for controlling the boiling level of a liquid medium in a microwave oven. The acoustic emissions from the medium correlated with surface boiling is used to generate a feedback control signal proportional to the level of boiling of the medium. This signal is applied to a power controller to automatically and continuously vary the power applied to the oven to control the boiling at a selected level.

  18. Acoustic emission feedback control for control of boiling in a microwave oven

    SciTech Connect

    White, T.L.

    1990-05-02

    An acoustic emission based feedback system for controlling the boiling level of a liquid medium in a microwave oven is provided. The acoustic emissions from the medium correlated with surface boiling is used to generate a feedback control signal proportional to the level of boiling of the medium. This signal is applied to a power controller to automatically and continuously vary the power applied to the oven to control the boiling at a selected level. 2 figs.

  19. Acoustic emission feedback control for control of boiling in a microwave oven

    DOEpatents

    White, Terry L.

    1991-01-01

    An acoustic emission based feedback system for controlling the boiling level of a liquid medium in a microwave oven is provided. The acoustic emissions from the medium correlated with surface boiling is used to generate a feedback control signal proportional to the level of boiling of the medium. This signal is applied to a power controller to automatically and continuoulsly vary the power applied to the oven to control the boiling at a selected level.

  20. 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…

  1. A system of counteracting feedback loops regulates Cdc42p activity during spontaneous cell polarization.

    PubMed

    Ozbudak, Ertugrul M; Becskei, Attila; van Oudenaarden, Alexander

    2005-10-01

    Cellular polarization is often a response to distinct extracellular or intracellular cues, such as nutrient gradients or cortical landmarks. However, in the absence of such cues, some cells can still select a polarization axis at random. Positive feedback loops promoting localized activation of the GTPase Cdc42p are central to this process in budding yeast. Here, we explore spontaneous polarization during bud site selection in mutant yeast cells that lack functional landmarks. We find that these cells do not select a single random polarization axis, but continuously change this axis during the G1 phase of the cell cycle. This is reflected in traveling waves of activated Cdc42p which randomly explore the cell periphery. Our integrated computational and in vivo analyses of these waves reveal a negative feedback loop that competes with the aforementioned positive feedback loops to regulate Cdc42p activity and confer dynamic responsiveness on the robust initiation of cell polarization.

  2. 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.

  3. Effects of voice style, noise level, and acoustic feedback on objective and subjective voice evaluations

    PubMed Central

    Bottalico, Pasquale; Graetzer, Simone; Hunter, Eric J.

    2015-01-01

    Speakers adjust their vocal effort when communicating in different room acoustic and noise conditions and when instructed to speak at different volumes. The present paper reports on the effects of voice style, noise level, and acoustic feedback on vocal effort, evaluated as sound pressure level, and self-reported vocal fatigue, comfort, and control. Speakers increased their level in the presence of babble and when instructed to talk in a loud style, and lowered it when acoustic feedback was increased and when talking in a soft style. Self-reported responses indicated a preference for the normal style without babble noise. PMID:26723357

  4. Performance analysis of approximate Affine Projection Algorithm in acoustic feedback cancellation.

    PubMed

    Nikjoo S, Mohammad; Seyedi, Amir; Tehrani, Arash Saber

    2008-01-01

    Acoustic feedback is an annoying problem in several audio applications and especially in hearing aids. Adaptive feedback cancellation techniques have attracted recent attention and show great promise in reducing the deleterious effects of feedback. In this paper, we investigated the performance of a class of adaptive feedback cancellation algorithms viz. the approximated Affine Projection Algorithms (APA). Mixed results were obtained with the natural speech and music data collected from five different commercial hearing aids in a variety of sub-oscillatory and oscillatory feedback conditions. The performance of the approximated APA was significantly better with music stimuli than natural speech stimuli.

  5. Charge-driven feedback loop in the resonance fluorescence of a single quantum dot

    NASA Astrophysics Data System (ADS)

    Merkel, B.; Kurzmann, A.; Schulze, J.-H.; Strittmatter, A.; Geller, M.; Lorke, A.

    2017-03-01

    We demonstrate a feedback loop that manifests itself in a strong hysteresis and bistability of the exciton resonance fluorescence signal. Field ionization of photogenerated quantum dot excitons leads to the formation of a charged interface layer that drags the emission line along over a frequency range of more than 30 GHz . These measurements are well described by a rate equation model. With a time-resolved resonance fluorescence measurement we determined the buildup times for the hole gas in the orders of milliseconds. This internal charge-driven feedback loop could be used to reduce the spectral wandering in the emission spectra of single self-assembled quantum dots.

  6. 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…

  7. Interlinked dual-time feedback loops can enhance robustness to stochasticity and persistence of memory

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

    Multiple interlinked positive feedback loops shape the stimulus responses of various biochemical systems, such as the cell cycle or intracellular Ca2+ release. Recent studies with simplified models have identified two advantages of coupling fast and slow feedback loops. This dual-time structure enables a fast response while enhancing resistances of responses and bistability to stimulus noise. We now find that (1) the dual-time structure similarly confers resistance to internal noise due to molecule number fluctuations, and (2) model variants with altered coupling, which better represent some specific biochemical systems, share all the above advantages. We also develop a similar bistable model with coupling of a fast autoactivation loop to a slow loop. This model’s topology was suggested by positive feedback proposed to play a role in long-term synaptic potentiation (LTP). The advantages of fast response and noise resistance are also present in this autoactivation model. Empirically, LTP develops resistance to reversal over ˜1h . The model suggests this resistance may result from increased amounts of synaptic kinases involved in positive feedback.

  8. 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.

  9. 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.

  10. 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

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

    NASA Astrophysics Data System (ADS)

    Han, Wang; Maomao, Sun

    2014-04-01

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

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

    PubMed

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

    2015-03-01

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

  13. Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation

    PubMed Central

    Lysyansky, Borys; Rosenblum, Michael; Pikovsky, Arkady; Tass, Peter A.

    2017-01-01

    High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson’s disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS. PMID:28273176

  14. 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.

  15. Self-Injection-Locked Magnetron as an Active Ring Resonator Side Coupled to a Waveguide With a Delayed Feedback Loop

    NASA Astrophysics Data System (ADS)

    Bliokh, Y. P.; Krasik, Y. E.; Felsteiner, J.

    2012-01-01

    The theoretical analysis and numerical simulations of the magnetron operation with a feedback loop were performed assuming that the delay of the electromagnetic wave propagating in the loop is constant whereas the phase of the complex feedback reflection coefficient is varied. Results of simulations showed that by a proper adjustment of values of the time delay and phase of reflection coefficient that determines phase matching between the waves in the resonator and feedback loop, one can increase the magnetron's output power significantly without any other additional measures.

  16. 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.

  17. Control of stem cell homeostasis via interlocking microRNA and microProtein feedback loops.

    PubMed

    Brandt, Ronny; Xie, Yakun; Musielak, Thomas; Graeff, Moritz; Stierhof, York-Dieter; Huang, Hai; Liu, Chun-Ming; Wenkel, Stephan

    2013-01-01

    Stem cells in the shoot apex of plants produce cells required for the formation of new leaves. Adult leaves are composed of multiple tissue layers arranged along the dorso-ventral (adaxial/abaxial) axis. Class III homeodomain leucine zipper (HD-ZIPIII) transcription factors play an important role in the set-up of leaf polarity in plants. Loss of HD-ZIPIII function results in strongly misshapen leaves and in severe cases fosters the consumption of the apical stem cells, thus causing a growth arrest in mutant plants. HD-ZIPIII mRNA is under tight control by microRNAs 165/166. In addition to the microRNA-action a second layer of regulation is established by LITTLE ZIPPER (ZPR)-type microProteins, which can interact with HD-ZIPIII proteins, forming attenuated protein complexes. Here we show that REVOLUTA (REV, a member of the HD-ZIPIII family) directly regulates the expression of ARGONAUTE10 (AGO10), ZPR1 and ZPR3. Because AGO10 was shown to dampen microRNA165/6 function, REV establishes a positive feedback loop on its own activity. Since ZPR-type microProteins are known to reduce HD-ZIPIII protein activity, REV concomitantly establishes a negative feedback loop. We propose that the interconnection of these microRNA/microProtein feedback loops regulates polarity set-up and stem cell activity in plants.

  18. Modeling feedback loops in the H-NS-mediated regulation of the Escherichia coli bgl operon.

    PubMed

    Radde, Nicole; Gebert, Jutta; Faigle, Ulrich; Schrader, Rainer; Schnetz, Karin

    2008-01-21

    The histone-like nucleoid-associated protein H-NS is a global transcriptional repressor that controls approximately 5% of all genes in Escherichia coli and other enterobacteria. H-NS binds to DNA with low specificity. Nonetheless, repression of some loci is exceptionally specific. Experimental data for the E. coli bgl operon suggest that highly specific repression is caused by regulatory feedback loops. To analyze whether such feedback loops can account for the observed specificity of repression, here a model was built based on expression data. The model includes several regulatory interactions, which are synergy of repression by binding of H-NS to two regulatory elements, an inverse correlation of the rate of repression by H-NS and transcription, and a threshold for positive regulation by anti-terminator BglG, which is encoded within the operon. The latter two regulatory interactions represent feedback loops in the model. The resulting system of equations was solved for the expression level of the operon and analyzed with respect to different promoter activities. This analysis demonstrates that a small (3-fold) increase of the bgl promoter activity results in a strong (80-fold) enhancement of bgl operon expression. Thus, the parameters included into the model are sufficient to simulate specific repression by H-NS.

  19. Sp1-CD147 positive feedback loop promotes the invasion ability of ovarian cancer.

    PubMed

    Zhao, Jing; Ye, Wei; Wu, Juan; Liu, Lijuan; Yang, Lina; Gao, Lu; Chen, Biliang; Zhang, Fanglin; Yang, Hong; Li, Yu

    2015-07-01

    CD147 is a novel cancer biomarker that has been confirmed to be overexpressed in ovarian carcinoma, which is significantly associated with poor prognosis. Although the Sp1 protein regulates the expression level of CD147, it remains unclear whether Sp1 phosphorylation plays a role in this regulation. A dual-luciferase assay revealed that T453 and T739 mutations decreased the activity of Sp1 binding to the promoter of CD147, followed by a decrease in CD147 mRNA and protein expression. Western blot analysis showed that CD147 promoted Sp1 phosphorylation at T453 and T739 through the PI3K/AKT and MAPK/ERK pathways. In addition, blocking the Sp1-CD147 positive feedback loop reduced the invasion ability of HO-8910pm cells. Immunohistochemical staining showed that the components of the feedback loop were overexpressed in ovarian cancer tissues. The correlation analysis revealed a significant correlation between phospho-Sp1 (T453), phospho-Sp1 (T739) and CD147 expression levels, with correlation coefficients of r=0.477 and r=0.461, respectively. Collectively, our results suggest that a Sp1-CD147 positive feedback loop plays a critical role in the invasion ability of ovarian cancer cells.

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

    PubMed

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

    2014-07-01

    We analyzed the microstructure of child-adult interaction during naturalistic, daylong, automatically labeled audio recordings (13,836 hr total) of children (8- to 48-month-olds) with and without autism. We found that an adult was more likely to respond when the child's vocalization was speech related rather than not speech related. In turn, a child's vocalization was more likely to be speech related if the child's previous speech-related vocalization had received an immediate adult response rather than no response. Taken together, these results are consistent with the idea that there is a social feedback loop between child and caregiver that promotes speech development. Although this feedback loop applies in both typical development and autism, children with autism produced proportionally fewer speech-related vocalizations, and the responses they received were less contingent on whether their vocalizations were speech related. We argue that such differences will diminish the strength of the social feedback loop and have cascading effects on speech development over time. Differences related to socioeconomic status are also reported.

  1. Effects of acoustic feedback training in elite-standard Para-Rowing.

    PubMed

    Schaffert, Nina; Mattes, Klaus

    2015-01-01

    Assessment and feedback devices have been regularly used in technique training in high-performance sports. Biomechanical analysis is mainly visually based and so can exclude athletes with visual impairments. The aim of this study was to examine the effects of auditory feedback on mean boat speed during on-water training of visually impaired athletes. The German National Para-Rowing team (six athletes, mean ± s, age 34.8 ± 10.6 years, body mass 76.5 ± 13.5 kg, stature 179.3 ± 8.6 cm) participated in the study. Kinematics included boat acceleration and distance travelled, collected with Sofirow at two intensities of training. The boat acceleration-time traces were converted online into acoustic feedback and presented via speakers during rowing (sections with and without alternately). Repeated-measures within-participant factorial ANOVA showed greater boat speed with acoustic feedback than baseline (0.08 ± 0.01 m·s(-1)). The time structure of rowing cycles was improved (extended time of positive acceleration). Questioning of athletes showed acoustic feedback to be a supportive training aid as it provided important functional information about the boat motion independent of vision. It gave access for visually impaired athletes to biomechanical analysis via auditory information. The concept for adaptive athletes has been successfully integrated into the preparation for the Para-Rowing World Championships and Paralympics.

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  3. 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.

  4. Trace observations of propagating slow magneto-acoustic disturbances in coronal loops

    NASA Astrophysics Data System (ADS)

    De Moortel, I.; Ireland, J.; Walsh, R. W.

    2002-06-01

    We study propagating disturbances in 38 coronal loops and give an overview of their properties using high cadence, 171 Å, TRACE data (JOP 83 & JOP 144). The majority of these outward propagating oscillations are found in the footpoints of large diffuse coronal loop structures, close to active regions. The disturbances travel outward with a propagation speed of the order of v ≍ 119+/-39 km/s. The variations in intensity are estimated to be roughly 4.1+/-1.6% of the background brightness and the propagating disturbances are found to be damped very quickly, within 8.6+/-3.8 Mm along the loop. Using a wavelet analysis, periods of the order of 282+/-93 seconds are found and the energy flux was estimated as 346+/-132 ergs/cm2s. It is suggested that these oscillations are slow magneto-acoustic waves propagating along the lower part of large, quiescent, coronal loops.

  5. 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.

  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 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.

  7. 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.

  8. 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.

  9. A state feedback electro-acoustic transducer for active control of acoustic impedance.

    PubMed

    Samejima, Toshiya

    2003-03-01

    In this paper, a new control system in which the acoustic impedance of an electro-acoustic transducer diaphragm can be actively varied by modifying design parameters is presented and its effectiveness is theoretically investigated. The proposed control system is based on a state-space description of the control system derived from an electrical equivalent circuit of an electro-acoustic transducer to which a differentiating circuit is connected, and is designed using modem control theory. The optimal quadratic regulator is used in the control system design, with its quadratic performance index formulated for producing desired acoustic impedance. Computer simulations indicate that the acoustic impedance of the diaphragm can be significantly varied over a wide frequency range that includes the range below the resonance frequency of the electro-acoustic transducer. A computer model of the proposed control system is used to illustrate its application to semi-active noise control in a duct. It is demonstrated that the proposed control system provides substantial reductions in the noise radiating from the outlet of the duct, both in the stiffness control range and in the mass control range.

  10. Impact of time delays on oscillatory dynamics of interlinked positive and negative feedback loops

    NASA Astrophysics Data System (ADS)

    Huang, Bo; Tian, Xinyu; Liu, Feng; Wang, Wei

    2016-11-01

    Interlinking a positive feedback loop (PFL) with a negative feedback loop (NFL) constitutes a typical motif in genetic networks, performing various functions in cell signaling. How time delay in feedback regulation affects the dynamics of such systems still remains unclear. Here, we investigate three systems of interlinked PFL and NFL with time delays: a synthetic genetic oscillator, a three-node circuit, and a simplified single-node model. The stability of steady states and the routes to oscillation in the single-node model are analyzed in detail. The amplitude and period of oscillations vary with a pointwise periodicity over a range of time delay. Larger-amplitude oscillations can be induced when the PFL has an appropriately long delay, in comparison with the PFL with no delay or short delay; this conclusion holds true for all the three systems. We unravel the underlying mechanism for the above effects via analytical derivation under a limiting condition. We also develop a stochastic algorithm for simulating a single reaction with two delays and show that robust oscillations can be maintained by the PFL with a properly long delay in the single-node system. This work presents an effective method for constructing robust large-amplitude oscillators and interprets why similar circuit architectures are engaged in timekeeping systems such as circadian clocks.

  11. Consecutive Positive Feedback Loops Create a Bistable Switch that Controls Preadipocyte-to-Adipocyte Conversion

    PubMed Central

    Park, Byung Ouk; Ahrends, Robert; Teruel, Mary N.

    2016-01-01

    SUMMARY Adipogenesis, or the conversion of proliferating preadipocytes into nondividing adipocytes, is an important part of the vertebrate weight-maintenance program. It is not yet understood how and when an irreversible transition occurs into a distinct state capable of accumulating lipid. Here, we use single-cell fluorescence imaging to show that an all-or-none switch is induced before lipid accumulation occurs. Conversion begins by glucocorticoid and cAMP signals raising C/EBPβ levels above a critical threshold, triggering three consecutive positive feedback loops: from PPARγ to C/EBPα, then to C/EBPβ, and last to the insulin receptor. Experiments and modeling show that these feedbacks create a robust, irreversible transition to a terminally differentiated state by rejecting short- and low-amplitude stimuli. After the differentiation switch is triggered, insulin controls fat accumulation in a graded fashion. Altogether, our study introduces a regulatory motif that locks cells in a differentiated state by engaging a sequence of positive feedback loops. PMID:23063366

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

    PubMed Central

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

    2016-01-01

    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 roles 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

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

    NASA Astrophysics Data System (ADS)

    Banerjee, Subhasis; Bose, Indrani

    2008-12-01

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

  14. 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.

  15. Coherently amplified negative feedback loop as a model for NF-kappaB oscillations

    NASA Astrophysics Data System (ADS)

    Joo, Jaewook

    2010-03-01

    The cells secrets various signaling molecules as a response to an external signal and modulate its own signaling processes. The precise role of this autocrine and/or paracrine signaling on cell information processing is mostly unknown. We will present the effect of TNF alpha autocrine signaling on NF-kappaB oscillations, using a simplified model of coherently amplified negative feedback loop. We will discuss the bifurcation diagram (i.e., dose-response curve), especially the robustness and the tenability of the period of NF-kappaB oscillations. Finally, we will compare the results from the above model with those from a previous model of time-delayed negative feedback alone.

  16. 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

    2011-09-07

    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.

  17. Enhancement and suppression of opto-acoustic parametric interactions using optical feedback

    SciTech Connect

    Zhang Zhongyang; Zhao Chunnong; Ju, L.; Blair, D. G.

    2010-01-15

    A three mode opto-acoustic parametric amplifier (OAPA) is created when two orthogonal optical modes in a high finesse optical cavity are coupled via an acoustic mode of the cavity mirror. Such interactions are predicted to occur in advanced long baseline gravitational wave detectors. They can have high positive gain, which leads to strong parametric instability. Here we show that an optical feedback scheme can enhance or suppress the parametric gain of an OAPA, allowing exploration of three-mode parametric interactions, especially in cavity systems that have insufficient optical power to achieve spontaneous instability. We derive analytical equations and show that optical feedback is capable of controlling predicted instabilities in advanced gravitational wave detectors within a time scale of 13approx10 s.

  18. Pulse oximeter improvement with an ADC-DAC feedback loop and a radial reflectance sensor.

    PubMed

    Thompson, David; Wareing, Austin; Day, Dwight; Warren, Steve

    2006-01-01

    Pulse oximeter circuitry must meet several design constraints, including the ability to separate a small pulsatile signal component from a large signal baseline. This paper describes pulse oximeter design changes that produced order-of-magnitude improvements in signal quality. The primary changes were (a) the replacement of an analog sample-and-hold-based differentiator circuit with an ADC-DAC feedback loop and (b) the replacement of a side-by-side reflectance sensor design with a radial sensor arrangement that maximizes the pulsatile-to-baseline signal ratio.

  19. Dammann-grating-based passive phase locking by an all-optical feedback loop.

    PubMed

    Yang, Yifeng; Liu, Houkang; Zheng, Ye; Hu, Man; Liu, Chi; Qi, Yunfeng; He, Bing; Zhou, Jun; Wei, Yunrong; Lou, Qihong

    2014-02-01

    A Dammann grating is used as a spatial filter for a passive coherent beam combination (CBC) of three Yb-doped fiber amplifiers with an all-optical feedback loop. Using this diffractive-optics-based spatial filtering technique, we demonstrate CBC with 20 W output power, and the visibility of the far-field interference pattern is up to 88.7%. Measurements suggest that this approach is robust with respect to laboratory environment perturbations, and it can scale to high powers and large arrays.

  20. 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.

  1. 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

  2. Stress-specific response of the p53-Mdm2 feedback loop

    PubMed Central

    2010-01-01

    Background The p53 signalling pathway has hundreds of inputs and outputs. It can trigger cellular senescence, cell-cycle arrest and apoptosis in response to diverse stress conditions, including DNA damage, hypoxia and nutrient deprivation. Signals from all these inputs are channeled through a single node, the transcription factor p53. Yet, the pathway is flexible enough to produce different downstream gene expression patterns in response to different stresses. Results We construct a mathematical model of the negative feedback loop involving p53 and its inhibitor, Mdm2, at the core of this pathway, and use it to examine the effect of different stresses that trigger p53. In response to DNA damage, hypoxia, etc., the model exhibits a wide variety of specific output behaviour - steady states with low or high levels of p53 and Mdm2, as well as spiky oscillations with low or high average p53 levels. Conclusions We show that even a simple negative feedback loop is capable of exhibiting the kind of flexible stress-specific response observed in the p53 system. Further, our model provides a framework for predicting the differences in p53 response to different stresses and single nucleotide polymorphisms. PMID:20624280

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

    PubMed

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

    2012-06-01

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

  4. A feedback loop regulates splicing of the spinal muscular atrophy-modifying gene, SMN2.

    PubMed

    Jodelka, Francine M; Ebert, Allison D; Duelli, Dominik M; Hastings, Michelle L

    2010-12-15

    Spinal muscular atrophy (SMA) is a neurological disorder characterized by motor neuron degeneration and progressive muscle paralysis. The disease is caused by a reduction in survival of motor neuron (SMN) protein resulting from homozygous deletion of the SMN1 gene. SMN protein is also encoded by SMN2. However, splicing of SMN2 exon 7 is defective, and consequently, the majority of the transcripts produce a truncated, unstable protein. SMN protein itself has a role in splicing. The protein is required for the biogenesis of spliceosomal snRNPs, which are essential components of the splicing reaction. We now show that SMN protein abundance affects the splicing of SMN2 exon 7, revealing a feedback loop inSMN expression. The reduced SMN protein concentration observed in SMA samples and in cells depleted of SMN correlates with a decrease in cellular snRNA levels and a decrease in SMN2 exon 7 splicing. Furthermore, altering the relative abundance or activity of individual snRNPs has distinct effects on exon 7 splicing, demonstrating that core spliceosomal snRNPs influence SMN2 alternative splicing. Our results identify a feedback loop in SMN expression by which low SMN protein levels exacerbate SMN exon 7 skipping, leading to a further reduction in SMN protein. These results imply that a modest increase in SMN protein abundance may cause a disproportionately large increase in SMN expression, a finding that is important for assessing the therapeutic potential of SMA treatments and understanding disease pathogenesis.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. A DNA break– and phosphorylation-dependent positive feedback loop promotes immunoglobulin class-switch recombination

    PubMed Central

    Vuong, Bao Q; Ucher, Anna J; Donghia, Nina M; Gu, Xiwen; Nicolas, Laura; Nowak, Urszula; Rahman, Numa; Strout, Matthew P; Mills, Kevin D; Stavnezer, Janet; Chaudhuri, Jayanta

    2014-01-01

    The ability of activation-induced cytidine deaminase (AID) to efficiently mediate class-switch recombination (CSR) is dependent on its phosphorylation at Ser38; however, the trigger that induces AID phosphorylation and the mechanism by which phosphorylated AID drives CSR have not been elucidated. Here we found that phosphorylation of AID at Ser38 was induced by DNA breaks. Conversely, in the absence of AID phosphorylation, DNA breaks were not efficiently generated at switch (S) regions in the immunoglobulin heavy-chain locus (Igh), consistent with a failure of AID to interact with the endonuclease APE1. Additionally, deficiency in the DNA-damage sensor ATM impaired the phosphorylation of AID at Ser38 and the interaction of AID with APE1. Our results identify a positive feedback loop for the amplification of DNA breaks at S regions through the phosphorylation- and ATM-dependent interaction of AID with APE1. PMID:24097111

  10. 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.

  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. Acoustic Power Suppression of a Panel Structure Using H∞OUTPUT Feedback Control

    NASA Astrophysics Data System (ADS)

    SIVRIOGLU, S.; TANAKA, N.; YUKSEK, I.

    2002-01-01

    This paper presents a robust control system design for suppressing the radiated acoustic power emitted from a vibrating planar structure, and spillover effect caused by neglected high-frequency modes. A state-space model of a simply supported panel structure is derived and an output equation is formed based on the one-dimensional PVDF film sensors. An output feedback H∞control is designed by introducing a multiplicative perturbation which represents unmodelled high-frequency dynamics in the control system. The simulation and experimental results demonstrated significant decrease in sound radiation for the considered structural power modes in control.

  13. Implementation of distributed feedback fiber laser sensor for acoustic measurements in hydraulic fracturing

    NASA Astrophysics Data System (ADS)

    Chen, Rongzhang; Yan, Aidong; Zaghloul, Mohamed A. S.; Lu, Guanyi; Bunger, Andrew P.; Miller, Gary A.; Cranch, Geoffrey A.; Chen, Kevin P.

    2016-09-01

    A distributed feedback (DFB) fiber laser strain sensor was implemented to measure acoustic emission induced by the hydraulic fracturing process. A study of practical sensor mounting configurations and their characteristics was carried out to find a practical solution. Combining the suitable mounting configuration and ultrahigh strain sensitivity of the DFB fiber laser, the evolution of the hydraulic fracturing process was well monitored. This study shows that fiber lasers can be useful alternatives to piezoelectric sensors in the field of hydraulic fracturing for gas and oil extraction.

  14. Activation of AKT pathway by Nrf2/PDGFA feedback loop contributes to HCC progression.

    PubMed

    Liu, Danyang; Zhang, Yonglong; Wei, Yingze; Liu, Guoyuan; Liu, Yufeng; Gao, Qiongmei; Zou, Liping; Zeng, Wenjiao; Zhang, Nong

    2016-10-04

    Nuclear factor erythroid-2-related factor 2 (Nrf2), a master transcription factor in the antioxidant response, has been found to be ubiquitously expressed in various cancer cells and in the regulation tumor proliferation, invasion, and chemoresistance activities. The regulatory roles of Nrf2 in controlling Hepatocellular carcinoma (HCC) progression remain unclear. In this study, we demonstrated that Nrf2 was significantly elevated in HCC cells and tissues and was correlated with poor prognosis of HCCs. Consistently, Nrf2 significantly promoted HCC cell growth both in vitro and in vivo. Further investigation suggested a novel association of Nrf2 with Platelet-Derived Growth Factor-A (PDGFA). Nrf2 promoted PDGFA transcription by recruiting specificity protein 1 (Sp1) to its promoter, resulting in increased activation of the AKT/p21 pathway and cell cycle progression of HCC cells. As a feedback loop, PDGFA enhanced Nrf2 expression and activation in an AKT dependent manner. In line with these findings, expression of Nrf2 and PDGFA were positively correlated in HCC tissues. Taken together, this study uncovers a novel mechanism of the Nrf2/PDGFA regulatory loop that is crucial for AKT-dependent HCC progression, and thereby provides potential targets for HCC therapy.

  15. KAYAK-α modulates circadian transcriptional feedback loops in Drosophila pacemaker neurons.

    PubMed

    Ling, Jinli; Dubruille, Raphaëlle; Emery, Patrick

    2012-11-21

    Circadian rhythms are generated by well-conserved interlocked transcriptional feedback loops in animals. In Drosophila, the dimeric transcription factor CLOCK/CYCLE (CLK/CYC) promotes period (per), timeless (tim), vrille (vri), and PAR-domain protein 1 (Pdp1) transcription. PER and TIM negatively feed back on CLK/CYC transcriptional activity, whereas VRI and PDP1 negatively and positively regulate Clk transcription, respectively. Here, we show that the α isoform of the Drosophila FOS homolog KAYAK (KAY) is required for normal circadian behavior. KAY-α downregulation in circadian pacemaker neurons increases period length by 1.5 h. This behavioral phenotype is correlated with decreased expression of several circadian proteins. The strongest effects are on CLK and the neuropeptide PIGMENT DISPERSING FACTOR, which are both under VRI and PDP1 control. Consistently, KAY-α can bind to VRI and inhibit its interaction with the Clk promoter. Interestingly, KAY-α can also repress CLK activity. Hence, in flies with low KAY-α levels, CLK derepression would partially compensate for increased VRI repression, thus attenuating the consequences of KAY-α downregulation on CLK targets. We propose that the double role of KAY-α in the two transcriptional loops controlling Drosophila circadian behavior brings precision and stability to their oscillations.

  16. Activation of AKT pathway by Nrf2/PDGFA feedback loop contributes to HCC progression

    PubMed Central

    Wei, Yingze; Liu, Guoyuan; Liu, Yufeng; Gao, Qiongmei; Zou, Liping; Zeng, Wenjiao; Zhang, Nong

    2016-01-01

    Nuclear factor erythroid-2-related factor 2 (Nrf2), a master transcription factor in the antioxidant response, has been found to be ubiquitously expressed in various cancer cells and in the regulation tumor proliferation, invasion, and chemoresistance activities. The regulatory roles of Nrf2 in controlling Hepatocellular carcinoma (HCC) progression remain unclear. In this study, we demonstrated that Nrf2 was significantly elevated in HCC cells and tissues and was correlated with poor prognosis of HCCs. Consistently, Nrf2 significantly promoted HCC cell growth both in vitro and in vivo. Further investigation suggested a novel association of Nrf2 with Platelet-Derived Growth Factor-A (PDGFA). Nrf2 promoted PDGFA transcription by recruiting specificity protein 1 (Sp1) to its promoter, resulting in increased activation of the AKT/p21 pathway and cell cycle progression of HCC cells. As a feedback loop, PDGFA enhanced Nrf2 expression and activation in an AKT dependent manner. In line with these findings, expression of Nrf2 and PDGFA were positively correlated in HCC tissues. Taken together, this study uncovers a novel mechanism of the Nrf2/PDGFA regulatory loop that is crucial for AKT-dependent HCC progression, and thereby provides potential targets for HCC therapy. PMID:27588483

  17. A Positive Autoregulatory BDNF Feedback Loop via C/EBPβ Mediates Hippocampal Memory Consolidation

    PubMed Central

    Bambah-Mukku, Dhananjay; Travaglia, Alessio; Chen, Dillon Y.; Pollonini, Gabriella

    2014-01-01

    Little is known about the temporal progression and regulation of the mechanisms underlying memory consolidation. Brain-derived-neurotrophic-factor (BDNF) has been shown to mediate the maintenance of memory consolidation, but the mechanisms of this regulation remain unclear. Using inhibitory avoidance (IA) in rats, here we show that a hippocampal BDNF-positive autoregulatory feedback loop via CCAAT-enhancer binding protein β (C/EBPβ) is necessary to mediate memory consolidation. At training, a very rapid, learning-induced requirement of BDNF accompanied by rapid de novo translation controls the induction of a persistent activation of cAMP-response element binding-protein (CREB) and C/EBPβ expression. The latter, in turn, controls an increase in expression of bdnf exon IV transcripts and BDNF protein, both of which are necessary and, together with the initial BDNF requirement, mediate memory consolidation. The autoregulatory loop terminates by 48 h after training with decreased C/EBPβ and pCREB and increased methyl-CpG binding protein-2, histone-deacetylase-2, and switch-independent-3a binding at the bdnf exon IV promoter. PMID:25209292

  18. A Diagnosis-Prognosis Feedback Loop for Improved Performance Under Uncertainties

    NASA Technical Reports Server (NTRS)

    Leser, Patrick E.; Warner, James E.

    2017-01-01

    The feed-forward relationship between diagnosis and prognosis is the foundation of both aircraft structural health management and the digital twin concept. Measurements of structural response are obtained either in-situ with mounted sensor networks or offline using more traditional techniques (e.g., nondestructive evaluation). Diagnosis algorithms process this information to detect and quantify damage and then feed this data forward to a prognostic framework. A prognosis of the structure's future operational readiness (e.g., remaining useful life or residual strength) is then made and is used to inform mission- critical decision-making. Years of research have been devoted to improving the elements of this process, but the process itself has not changed significantly. Here, a new approach is proposed in which prognosis information is not only fed forward for decision-making, but it is also fed back to the forthcoming diagnosis. In this way, diagnosis algorithms can take advantage of a priori information about the expected state of health, rather than operating in an uninformed condition. As a feasibility test, a diagnosis-prognosis feedback loop of this manner is demonstrated. The approach is applied to a numerical example in which fatigue crack growth is simulated in a simple aluminum alloy test specimen. A prognosis was derived from a set of diagnoses which provided feedback to a subsequent set of diagnoses. Improvements in accuracy and a reduction in uncertainty in the prognosis- informed diagnoses were observed when compared with an uninformed diagnostic approach.

  19. 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

  20. A Machine Tool Controller using Cascaded Servo Loops and Multiple Feedback Sensors per Axis

    SciTech Connect

    Weinert, G F; Hopkins, D J; Wulff, T A

    2004-03-19

    In the past, several of LLNL precision machine tools have been built with custom in-house designed machine tool controllers (CNC). In addition, many of these controllers have reached the end of their maintainable lifetime, limit future machine application enhancements, have poor operator interfaces and are a potential single point of failure for the machine tool. There have been attempts to replace some of these custom controllers with commercial controller products, unfortunately, this has occurred with only limited success. Many commercial machine tool controllers have the following undesirable characteristics, a closed architecture (use as the manufacturer intended and not as LLNL would desire), allow only a single feedback device per machine axis and have limited servo axis compensation calculations. Technological improvements in recent years have allowed for the development of some commercial machine tool controllers that are more open in their architecture and have the power to solve some of these limitations. In this paper, we exploit the capabilities of one of these controllers to allow it to process multiple feedback sensors for tool tip calculations in real time and to extend the servo compensation capabilities by cascading several standard motor compensation loops.

  1. 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

  2. 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.

  3. 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)

  4. Shaping volumetric light distribution through turbid media using real-time three-dimensional opto-acoustic feedback.

    PubMed

    Deán-Ben, X Luís; Estrada, Héctor; Razansky, Daniel

    2015-02-15

    Focusing light through turbid media represents a highly fascinating challenge in modern biophotonics. The unique capability of opto-acoustics for high-resolution imaging of light absorption contrast in deep tissues can provide a natural and efficient feedback to control light delivery in a scattering medium. While the basic feasibility of using opto-acoustic readings as a feedback mechanism for wavefront shaping has been recently reported, the suggested approaches may require long acquisition times, making them challenging to be translated into realistic tissue environments. In an attempt to significantly accelerate dynamic wavefront shaping capabilities, we present here a feedback-based approach using real-time three-dimensional opto-acoustic imaging assisted with genetic-algorithm-based optimization. The new technique offers robust performance in the presence of noisy measurements and can simultaneously control the scattered wave field in an entire volumetric region.

  5. A novel method of improving sound quality and reducing acoustic feedback in hearing aids

    NASA Astrophysics Data System (ADS)

    Killion, Mead; French, John; Viranyi, Steve; Preves, David

    2002-05-01

    Most current hearing aids have relatively narrow bandwidths, when compared to high-fidelity equipment, and exhibit undamped peaks because the peaks are considered less troublesome than the problem of wax-clogged dampers. Attempting to make hearing aids wider band has typically resulted in increased acoustic feedback problems. The recent availability of an off-the-shelf digital hearing aid integrated circuit amplifier, which contains several biquad filters, when used with special software, automatically detects and suppresses peaks. The filters then further flatten and extend the hearing aid frequency response to 16 kHz, while the appropriate CORFIG correction is added to the frequency response, producing a transparent sound. Open ear versus aided KEMAR recordings were produced using a live jazz trio and a string quartet. The sound quality ratings for eight commercially available digital hearing aids were obtained from several different listening panels. The new response equalization proved advantageous in all cases. The effects of eliminating the peaks in the response on maximum real ear gain achievable before onset of acoustic feedback oscillation will be reported.

  6. Investigation of all-optical latching operation of a monolithically integrated SOA-MZI with a feedback loop.

    PubMed

    Naito, Yusuke; Shimizu, Satoshi; Kato, Tomoyuki; Kobayashi, Kohroh; Uenohara, Hiroyuki

    2012-12-10

    We have investigated an all-optical set/reset and latching operation using a monolithically integrated InP-based semiconductor optical amplifier type Mach-Zehnder interferometer with a feedback loop. In simulation, operation conditions when both set and reset are possible was estimated for input light pulse with a FWHM of 31 and 12.5 ps, and the tolerance of the CW probe light and feedback loop loss becomes large with increasing the input light pulse power. In addition, the loop length could be longer than the distance of the light propagating in one bit pulse because of the longer carrier recovery time than one bit time duration. Moreover, we successfully achieved set/reset operation with 34- and 18-ps wide set/reset pulses.

  7. Peatland plant communities under global change: negative feedback loops counteract shifts in species composition.

    PubMed

    Hedwall, Per-Ola; Brunet, Jörg; Rydin, Håkan

    2017-01-01

    Mires (bogs and fens) are nutrient-limited peatland ecosystems, the vegetation of which is especially sensitive to nitrogen deposition and climate change. The role of mires in the global carbon cycle, and the delivery of different ecosystem services can be considerably altered by changes in the vegetation, which has a strong impact on peat-formation and hydrology. Mire ecosystems are commonly open with limited canopy cover but both nitrogen deposition and increased temperatures may increase the woody vegetation component. It has been predicted that such an increase in tree cover and the associated effects on light and water regimes would cause a positive feed-back loop with respect to the ground vegetation. None of these effects, however, have so far been confirmed in large-scale spatiotemporal studies. Here we analyzed data pertaining to mire vegetation from the Swedish National Forest Inventory collected from permanent sample plots over a period of 20 yr along a latitudinal gradient covering 14°. We hypothesized that the changes would be larger in the southern parts as a result of higher nitrogen deposition and warmer climate. Our results showed an increase in woody vegetation with increases in most ericaceous dwarf-shrubs and in the basal area of trees. These changes were, in contrast to our expectations, evenly distributed over most of the latitudinal gradient. While nitrogen deposition is elevated in the south, the increase in temperatures during recent decades has been larger in the north. Hence, we suggest that different processes in the north and south have produced similar vegetation changes along the latitudinal gradient. There was, however, a sharp increase in compositional change at high deposition, indicating a threshold effect in the response. Instead of a positive feed-back loop caused by the tree layer, an increase in canopy cover reduced the changes in composition of the ground vegetation, whereas a decrease in canopy cover lead to larger changes

  8. Fast half-loop maneuvers for a high alpha fighter aircraft using a singular perturbation feedback control law

    NASA Technical Reports Server (NTRS)

    Garrett, Frederick E., Jr.; Stalford, Harold L.

    1989-01-01

    Singular perturbation analysis is used to derive an outer layer feedback control law for a high alpha fighter aircraft to perform the half-loop maneuver. Pitch rate and angle of attack are treated as fast variables in the derivation. Bang-bang controls are derived to transfer the aircraft state from trim to the outer layer and from the outer layer to specified final half-loop values. The pitch rate is treated as a varibale faster than the angle of attack in the transfer of the state to and from the outer layer. A simulation of the derived control law is conducted at Mach 0.6 and 15,000 feet altitude. The half-loop was performed in 13.12 seconds. It is compared with a NASA pilot simulated half-loop maneuver which took 22.42 seconds for the same initial conditions.

  9. Propagating slow magneto-acoustic waves in coronal loops as seen from trace and cds

    NASA Astrophysics Data System (ADS)

    Prasad Samayamanthula, Krishna; Banerjee, Dipankar; Gupta, Girjesh R.

    Propagating intensity disturbances along various Active region loop structures with projected speeds less than and close to acoustic speeds, now commonly called magneto-acoustic waves, are proposed to be photospheric p-modes leaking into solar atmosphere. Though there is a wide range of periodicities observed, the 3 min. and 5 min. periodicities, which are character-istic of sunspot umbral and penumbral regions lifted their importance of study. Simultaneous observations of these waves at different heights from photosphere, through transition region to corona will give us direct evidence for their involvement and contribution to coronal heating. AR 10457 had been extensively studied for the presence of such propagating oscillations, when it is on-disk, on 11th September 2003, using the CDS/SoHO, TRACE, and MDI data of JOP 165 campaign. Different periodicities are found and the resonance feature in the periodicity is observed in few locations, but the speeds are found to be quite low(< 20 km/s). Comparison will be made between sunspot and non-sunspot linked open structures. There is also a signature of decelerating propagation in a structure. Significance of the results in the context of coronal heating and future observations with SDO will be discussed.

  10. A feedback regulatory loop between methyltransferase PRMT1 and orphan receptor TR3

    PubMed Central

    Lei, Na-zi; Zhang, Xiao-yan; Chen, Hang-zi; Wang, Yuan; Zhan, Yan-yan; Zheng, Zhong-hui; Shen, Yue-mao; Wu, Qiao

    2009-01-01

    PRMT1, an arginine methyltransferase, plays an important role in numerous cellular processes. In this study, we demonstrate a feedback regulatory loop between PRMT1 and the orphan receptor TR3. Unlike another orphan receptor HNF4, TR3 is not methylated by PRMT1 although they physically interact with each other. By delaying the TR3 protein degradation, PRMT1 binding leads to the elevation of TR3 cellular protein level, thereby enhances the DNA binding and transactivation activity of TR3 in a non-methyltransferase manner. Another coactivator SRC-2 acts synergistically with PRMT1 to regulate TR3 functions. In turn, TR3 binding to the catalytic domain of PRMT1 causes an inhibition of the PRMT1 methyltransferase activity. This repression results in the functional changes in some of PRMT1 substrates, including STAT3 and Sam68. The negative regulation of PRMT1 by TR3 was further confirmed in both TR3-knockdown cells and TR3-knockout mice with the use of an agonist for TR3. Taken together, our study not only identifies a regulatory role of PRMT1, independent on methyltransferase activity, in TR3 transactivation, but also characterizes a novel function of TR3 in the repression of PRMT1 methyltransferase activity. PMID:19095693

  11. A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory

    PubMed Central

    Mathew, Rebecca S; Tatarakis, Antonis; Rudenko, Andrii; Johnson-Venkatesh, Erin M; Yang, Yawei J; Murphy, Elisabeth A; Todd, Travis P; Schepers, Scott T; Siuti, Nertila; Martorell, Anthony J; Falls, William A; Hammack, Sayamwong E; Walsh, Christopher A; Tsai, Li-Huei; Umemori, Hisashi; Bouton, Mark E; Moazed, Danesh

    2016-01-01

    The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway. DOI: http://dx.doi.org/10.7554/eLife.22467.001 PMID:28001126

  12. TDP-43 regulates its mRNA levels through a negative feedback loop

    PubMed Central

    Ayala, Youhna M; De Conti, Laura; Avendaño-Vázquez, S Eréndira; Dhir, Ashish; Romano, Maurizio; D'Ambrogio, Andrea; Tollervey, James; Ule, Jernej; Baralle, Marco; Buratti, Emanuele; Baralle, Francisco E

    2011-01-01

    TAR DNA-binding protein (TDP-43) is an evolutionarily conserved heterogeneous nuclear ribonucleoprotein (hnRNP) involved in RNA processing, whose abnormal cellular distribution and post-translational modification are key markers of certain neurodegenerative diseases, such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. We generated human cell lines expressing tagged forms of wild-type and mutant TDP-43 and observed that TDP-43 controls its own expression through a negative feedback loop. The RNA-binding properties of TDP-43 are essential for the autoregulatory activity through binding to 3′ UTR sequences in its own mRNA. Our analysis indicated that the C-terminal region of TDP-43, which mediates TDP-43–hnRNP interactions, is also required for self-regulation. TDP-43 binding to its 3′ UTR does not significantly change the pre-mRNA splicing pattern but promotes RNA instability. Moreover, blocking exosome-mediated degradation partially recovers TDP-43 levels. Our findings demonstrate that cellular TDP-43 levels are under tight control and it is likely that disease-associated TDP-43 aggregates disrupt TDP-43 self-regulation, thus contributing to pathogenesis. PMID:21131904

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

    DOE PAGES

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

    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

  14. 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.

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

    PubMed Central

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

    2005-01-01

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

  16. 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.

  17. 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.

  18. Online Reconstruction and Calibration with Feedback Loop in the ALICE High Level Trigger

    NASA Astrophysics Data System (ADS)

    Rohr, David; Shahoyan, Ruben; Zampolli, Chiara; Krzewicki, Mikolaj; Wiechula, Jens; Gorbunov, Sergey; Chauvin, Alex; Schweda, Kai; Lindenstruth, Volker

    2016-11-01

    ALICE (A Large Heavy Ion Experiment) is one of the four large scale experiments at the Large Hadron Collider (LHC) at CERN. The High Level Trigger (HLT) is an online computing farm, which reconstructs events recorded by the ALICE detector in real-time. The most computing-intensive task is the reconstruction of the particle trajectories. The main tracking devices in ALICE are the Time Projection Chamber (TPC) and the Inner Tracking System (ITS). The HLT uses a fast GPU-accelerated algorithm for the TPC tracking based on the Cellular Automaton principle and the Kalman filter. ALICE employs gaseous subdetectors which are sensitive to environmental conditions such as ambient pressure and temperature and the TPC is one of these. A precise reconstruction of particle trajectories requires the calibration of these detectors. As our first topic, we present some recent optimizations to our GPU-based TPC tracking using the new GPU models we employ for the ongoing and upcoming data taking period at LHC. We also show our new approach to fast ITS standalone tracking. As our second topic, we present improvements to the HLT for facilitating online reconstruction including a new flat data model and a new data flow chain. The calibration output is fed back to the reconstruction components of the HLT via a feedback loop. We conclude with an analysis of a first online calibration test under real conditions during the Pb-Pb run in November 2015, which was based on these new features.

  19. Argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop.

    PubMed

    Golembo, M; Schweitzer, R; Freeman, M; Shilo, B Z

    1996-01-01

    Argos is a secreted molecule with an atypical EGF motif. It was recently shown to function as an inhibitor of the signaling triggered by the Drosophila EGF receptor (DER). In this work, we determine the contribution of Argos to the establishment of cell fates in the embryonic ventral ectoderm. Graded activation of DER is essential for patterning the ventral ectoderm. argos mutant embryos show expansion of ventral cell fates suggesting hyperactivation of the DER pathway. In the embryonic ventral ectoderm, argos is expressed in the ventralmost row of cells. We show that argos expression in the ventral ectoderm is induced by the DER pathway: argos is not expressed in DER mutant embryos, while it is ectopically expressed in the entire ventral ectoderm following ubiquitous activation of the DER pathway. argos expression appears to be triggered directly by the DER pathway, since induction can also be observed in cell culture, following activation of DER by its ligand, Spitz. Argos therefore functions in a sequential manner, to restrict the duration and level of DER signaling. This type of inhibitory feedback loop may represent a general paradigm for signaling pathways inducing diverse cell fates within a population of non-committed cells.

  20. NF-κB regulates neuronal ankyrin-G via a negative feedback loop

    PubMed Central

    König, Hans-Georg; Schwamborn, Robert; Andresen, Silke; Kinsella, Sinéad; Watters, Orla; Fenner, Beau; Prehn, Jochen H. M.

    2017-01-01

    The axon initial segment (AIS) is a neuronal compartment defined by ankyrin-G expression. We here demonstrate that the IKK-complex co-localizes and interacts with the cytoskeletal anchor protein ankyrin-G in immunoprecipitation and proximity-ligation experiments in cortical neurons. Overexpression of the 270 kDa variant of ankyrin-G suppressed, while gene-silencing of ankyrin-G expression increased nuclear factor-κB (NF-κB) activity in primary neurons, suggesting that ankyrin-G sequesters the transcription factor in the AIS. We also found that p65 bound to the ank3 (ankyrin-G) promoter sequence in chromatin immunoprecipitation analyses thereby increasing ank3 expression and ankyrin-G levels at the AIS. Gene-silencing of p65 or ankyrin-G overexpression suppressed ank3 reporter activity. Collectively these data demonstrate that p65/NF-κB controls ankyrin-G levels via a negative feedback loop, thereby linking NF-κB signaling with neuronal polarity and axonal plasticity. PMID:28181483

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

    PubMed

    Reed, Phil

    2016-03-01

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

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

    PubMed

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

    2015-08-11

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

  3. A Negative Feedback Loop Between Autophagy and Immune Responses in Mycobacterium leprae Infection.

    PubMed

    Ma, Yuelong; Zhang, Li; Lu, Jie; Shui, Tiejun; Chen, Jia; Yang, Jun; Yuan, Joanna; Liu, Yeqiang; Yang, Degang

    2017-01-01

    The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level. However, macrophages with high autophagy levels preferentially expressed lower levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor-α, and preferentially primed anti-inflammatory T cells responses, characterized by high IL-10 and low interferon-γ, granzyme B, and perforin responses. These anti-inflammatory T cells could suppress further induction of autophagy, leading to improved survival of intracellular M. leprae in infected macrophages. Therefore, these data demonstrated that although autophagy had a role in eliminating intracellular pathogens, the induction of autophagy resulted in anti-inflammatory immune responses, which suppressed autophagy in a negative feedback loop and allowed the persistence of M. leprae.

  4. Maternally Inherited Stable Intronic Sequence RNA Triggers a Self-Reinforcing Feedback Loop during Development.

    PubMed

    Tay, Mandy Li-Ian; Pek, Jun Wei

    2017-04-03

    Maternally inherited noncoding RNAs (ncRNAs) can regulate zygotic gene expression across generations [1-4]. Recently, many stable intronic sequence RNAs (sisRNAs), which are byproducts of pre-mRNA splicing, were found to be maternally deposited and persist till zygotic transcription in Xenopus and Drosophila [5-7]. In various organisms, sisRNAs can be in linear or circular conformations, and they have been suggested to regulate host gene expression [5-10]. It is unknown whether maternally deposited sisRNAs can regulate zygotic gene expression in the embryos. Here, we show that a maternally inherited sisRNA (sisR-4) from the deadpan locus is important for embryonic development in Drosophila. Mothers, but not fathers, mutant for sisR-4 produce embryos that fail to hatch. During embryogenesis, sisR-4 promotes transcription of its host gene (deadpan), which is essential for development. Interestingly, sisR-4 functions by activating an enhancer present in the intron where sisR-4 is encoded. We propose that a maternal sisRNA triggers expression of its host gene via a positive feedback loop during embryogenesis.

  5. Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway

    PubMed Central

    Zhou, Fen; Huang, Dengliang; Li, Yong; Hu, Guanghui; Rao, Hai; Lu, Quqin; Luo, Shiwen; Wang, Yao

    2017-01-01

    Suppressor of Fused (SuFu), one of the most conserved components of the Hedgehog (Hh) signaling, binds Gli transcription factors and impedes activation of target gene expression in mammalian cells. Despite the central importance of SuFu in the Hh pathway, little is known about SuFu regulation. In a previous study, we identified NIMA-related expressed kinase 2A (Nek2A) as a SuFu-interacting protein. Here, we show that Nek2A stabilizes SuFu through impairing ubiquitin/proteasome degradation of SuFu. In addition, Nek2A negatively regulates target genes of Hh signaling as well as Gli2 transcriptional activity. In turn, inhibition of Hh signaling by GANT61 diminishes mRNA and protein levels of Nek2A, and Hh agonist promotes transcription of NEK2A gene. Chromatin immunoprecipitation assays revealed that Gli1 and Gli2 directly bind to the promoter regions of NEK2A gene and induced its transcription. Thus, we uncovered one of the mechanisms by which Nek2A acts as a modulator of the Hh signaling pathway in the context of a novel negative-feedback loop, which may offer new insights into Gli-mediated Hh signaling regulation in development and human diseases. PMID:28035348

  6. Interlocking Feedback Loops Govern the Dynamic Behavior of the Floral Transition in Arabidopsis[W][OA

    PubMed Central

    Jaeger, Katja E.; Pullen, Nick; Lamzin, Sergey; Morris, Richard J.; Wigge, Philip A.

    2013-01-01

    During flowering, primordia on the flanks of the shoot apical meristem are specified to form flowers instead of leaves. Like many plants, Arabidopsis thaliana integrates environmental and endogenous signals to control the timing of reproduction. To study the underlying regulatory logic of the floral transition, we used a combination of modeling and experiments to define a core gene regulatory network. We show that FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1) act through FD and FD PARALOG to regulate the transition. The major floral meristem identity gene LEAFY (LFY) directly activates FD, creating a positive feedback loop. This network predicts flowering behavior for different genotypes and displays key properties of the floral transition, such as signal integration and irreversibility. Furthermore, modeling suggests that the control of TFL1 is important to flexibly counterbalance incoming FT signals, allowing a pool of undifferentiated cells to be maintained despite strong differentiation signals in nearby cells. This regulatory system requires TFL1 expression to rise in proportion to the strength of the floral inductive signal. In this network, low initial levels of LFY or TFL1 expression are sufficient to tip the system into either a stable flowering or vegetative state upon floral induction. PMID:23543784

  7. 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.

  8. Sideband locking of a single-section semiconductor distributed-feedback laser in an optical phase-lock loop.

    PubMed

    Satyan, Naresh; Vasilyev, Arseny; Liang, Wei; Rakuljic, George; Yariv, Amnon

    2009-11-01

    The bandwidth and performance of optical phase-lock loops (OPLLs) using single-section semiconductor lasers (SCLs) are severely limited by the nonuniform frequency modulation response of the lasers. It is demonstrated that this restriction is eliminated by the sideband locking of a single-section distributed-feedback SCL to a master laser in a heterodyne OPLL, thus enabling a delay-limited loop bandwidth. The lineshape of the phase-locked SCL output is characterized using a delayed self-heterodyne measurement.

  9. Towards Understanding the Star Formation-Feedback Loop in Galaxy Formation and Evolution

    NASA Astrophysics Data System (ADS)

    Kravtsov, Andrey

    We propose to carry out a comprehensive study of how star formation and feedback loop influences evolution of galaxies using a suite of ultra-high resolution cosmological simulations of galaxy formation using the Adaptive Mesh Refinement (AMR) approach implemented in the Adaptive Refinement Tree (ART) code. The simulations will result in the numerical models of galaxy evolution of unprecedented resolution and sophistication of the processes included. Our code includes treatment of a wide spectrum of processes critical for realistic modeling of galaxy formation from the primordial chemistry of hydrogen and helium species, radiative transfer of ionizing radiation, to the metallicity- dependent cooling, chemistry of molecular hydrogen on dust and treatment of radiative transfer of dissociating far ultraviolet radiation. The latter allows us to tie star formation with dense, molecular regions capable of self-shielding from heating radiation and avoid adopting arbitrary density and temperature thresholds for star formation. Simulations will also employ a new model for momentum injection due to radiation pressure exerted by young massive stars onto surrounding dust and gas. This early, pre-supernova feedback is critical to prompt dispersal of natal molecular clouds and regulating star formation efficiency and increasing efficiency of energy release by supernovae. The simulations proposed in this project will therefore treat the most important process to understanding the efficiency of baryon conversion to stars - the star formation - in the way most closely resembling the actual star formation observed in galaxies and stellar feedback model that is firmly rooted in observational evidence on how feedback operates in real molecular clouds. The simulations we propose will provide models of galaxy evolution during three important epochs in the history of the universe: (1) early evolution prior to and during the reionization of the universe (the first billion years of

  10. Polarization self-selection in a coherent beam combination system with an all-optical feedback loop.

    PubMed

    Liu, Houkang; He, Bing; Zhou, Jun; Liu, Chi; Dong, Jingxing; Wei, Yunrong; Lou, Qihong

    2012-09-20

    Polarization self-selection in passive phasing of four fiber amplifiers with an all-optical feedback loop is demonstrated. The polarization extinction ratio (PER) of the combined beam is increased, and the polarized direction is selected with the use of a polarization-maintaining (PM) isolator and some non-PM components. The best visibility of the interference patterns is observed at 95.2% and in the largest increment in the PER of the combined beam up to 7.4 dB. Results show that all PM components are unnecessary in the coherent beam combination with an all-optical feedback loop, whereas non-PM components have good potential to achieve high output power.

  11. Two different modes of oscillation in a gene transcription regulatory network with interlinked positive and negative feedback loops

    NASA Astrophysics Data System (ADS)

    Karmakar, Rajesh

    2016-12-01

    We study the oscillatory behavior of a gene regulatory network with interlinked positive and negative feedback loop. The frequency and amplitude are two important properties of oscillation. The studied network produces two different modes of oscillation. In one mode (mode-I), frequency of oscillation remains constant over a wide range of amplitude and in the other mode (mode-II) the amplitude of oscillation remains constant over a wide range of frequency. Our study reproduces both features of oscillations in a single gene regulatory network and shows that the negative plus positive feedback loops in gene regulatory network offer additional advantage. We identified the key parameters/variables responsible for different modes of oscillation. The network is flexible in switching between different modes by choosing appropriately the required parameters/variables.

  12. Acoustic and articulatory measures of sibilant production with and without auditory feedback from a cochlear implant.

    PubMed

    Matthies, M L; Svirsky, M; Perkell, J; Lane, H

    1996-10-01

    The articulator positions of a subject with a cochlear implant were measured with an electromagnetic midsagittal articulometer (EMMA) system with and without auditory feedback available to the subject via his implant. Acoustic analysis of sibilant productions included specific measures of their spectral properties as well as the F3 formant amplitude. More general postural characteristics of the utterances, such as speech rate and sound level, were measured as well. Because of the mechanical and aerodynamic interdependence of the articulators, the postural variables must be considered before attributing speech improvement to the selective correction of a phonemic target with the use of auditory feedback. The tongue blade position was related to the shape and central tendency of the /integral of/ spectra; however, changes in the spectral contrast between /s/ and /integral of/ were not related to changes in the more general postural variables of rate and sound level. These findings suggest that the cochlear implant is providing this subject with important auditory cues that he can use to monitor his speech and maintain the phonemic contrast between /s/ and /integral of/.

  13. 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.

  14. 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

    2012-10-07

    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.

  15. Methylglyoxal in cells elicits a negative feedback loop entailing transglutaminase 2 and glyoxalase 1.

    PubMed

    Lee, Der-Yen; Chang, Geen-Dong

    2014-01-01

    Glyoxalase 1 (GlxI) is the key enzyme that converts the highly reactive α-oxo-aldehydes into the corresponding α-hydroxy acids using l-glutathione as a cofactor. In our preliminary data, GlxI was identified as a substrate of transglutaminase 2 (TG2), a ubiquitous enzyme with multiple functions. According to the catalytic properties of TG2, protein cross-linking, polyamine conjugation, and/or deamidation are potential post-translational modifications. In this article, we have demonstrated that TG2 catalyzes either polyamine conjugation or deamidation to GlxI depending on the presence of polyamines or not. Deamidation leads to activation of GlxI while polyamine conjugation results in activation of GlxI as well as stabilization of GlxI against denaturation treatment. In cultured HeLa cells, methylglyoxal challenge causes increase in intracellular levels of reactive oxygen species (ROS) and calcium leading to TG2 activation and subsequent transamidation and activation of GlxI. The inhibition of TG2 significantly weakens the cell resistance to the methylglyoxal challenge. Thus, GlxI is a novel substrate of TG2 and is activated by TG2 in vitro and in cellulo. Exposure to methylglyoxal elicits a negative feedback loop entailing ROS, calcium, TG2 and GlxI, thus leading to attenuation of the increase in the methylglyoxal level. The results imply that cancer cells highly express TG2 or GlxI can endure the oxidative stress derived from higher glycolytic flux and may gain extra growth advantage from the aerobic glycolysis.

  16. Positive feedback loop of YB-1 interacting with Smad2 promotes liver fibrosis.

    PubMed

    Xiong, Panpan; Zhang, Jun; Xu, Diannan; Zhu, Jie; Li, Wenshuai; Liu, Jie; Liu, Fei

    2017-03-18

    Y-box binding protein (YB-1), known as a multifunctional cellular protein in various biological processes, was recently reported to be associated with liver fibrosis. The critical role of TGF-β/Smad signaling pathway in stimulating the transcription of fibrotic genes in fibroblasts have already been identified, however, whether and how YB-1 modulated liver fibrosis via TGF-β/Smad signaling pathway remains largely unknown. In our previous study, we proved that ectopic TGF-β was associated with YB-1 expression. Herein, by combining in vitro experiments in LX2 human hepatic stellate cells and in vivo studies by building CCl4 based mice liver fibrosis model, we showed that YB-1 and p-YB-1 were upregulated in liver fibrosis tissue, and YB-1 promoted the deposition of excess extracellular matrix. Mechanistically, Smad2, a key member in TGF-β signaling pathway, acted as a transcription factor that triggered YB-1 promoter, while on the other hand, p-YB-1 stabilized Smad2 by attenuating its ubiquitination. Knockdown of Smad2 could reduce YB-1 expression, which in turn shorter the half time of Smad2. Furthermore, the serine102 residue of YB-1 both affected its binding and stabilizing activity to Smad2. These finding demonstrated that YB-1 and Smad2 played as a positive feedback loop in promoting liver fibrosis. In conclusion, TGF-β signaling pathway may influence liver fibrosis by incorporating with YB-1, indicating that YB-1 could be a potential target for therapies against liver fibrosis.

  17. Effect of Insulin Feedback on Closed-Loop Glucose Control: A Crossover Study

    PubMed Central

    Ruiz, Jessica L.; Sherr, Jennifer L.; Cengiz, Eda; Carria, Lori; Roy, Anirban; Voskanyan, Gayane; Tamborlane, William V.; Weinzimer, Stuart A.

    2012-01-01

    Background Closed-loop (CL) insulin delivery systems utilizing proportional-integral-derivative (PID) controllers have demonstrated susceptibility to late postprandial hypoglycemia because of delays between insulin delivery and blood glucose (BG) response. An insulin feedback (IFB) modification to the PID algorithm has been introduced to mitigate this risk. We examined the effect of IFB on CL BG control. Methods Using the Medtronic ePID CL system, four subjects were studied for 24 h on PID control and 24 h during a separate admission with the IFB modification (PID + IFB). Target glucose was 120 mg/dl; meals were served at 8:00 AM, 1:00 PM, and 6:00 PM and were identical for both admissions. No premeal manual boluses were given. Reference BG excursions, defined as incremental glucose rise from premeal to peak, and postprandial BG area under the curve (AUC; 0–5 h) were compared. Results are reported as mean ± standard deviation. Results The PID + IFB control resulted in higher mean BG levels compared with PID alone (153 ± 54 versus 133 ± 56 mg/dl; p < .0001). Postmeal BG excursions (114 ± 28 versus 114 ± 47 mg/dl) and AUCs (285 ± 102 versus 255 ± 129 mg/dl/h) were similar under both conditions. Total insulin delivery averaged 57 ± 20 U with PID versus 45 ± 13 U with PID + IFB (p = .18). Notably, eight hypoglycemic events (BG < 60 mg/dl) occurred during PID control versus none during PID + IFB. Conclusions Addition of IFB to the PID controller markedly reduced the occurrence of hypoglycemia without increasing meal-related glucose excursions. Higher average BG levels may be attributable to differences in the determination of system gain (Kp) in this study. The prevention of postprandial hypoglycemia suggests that the PID + IFB algorithm may allow for lower target glucose selection and improved overall glycemic control. PMID:23063039

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

    PubMed

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

    2010-05-21

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

  19. High temperature acoustic levitator

    NASA Technical Reports Server (NTRS)

    Barmatz, M. B. (Inventor)

    1984-01-01

    A system is described for acoustically levitating an object within a portion of a chamber that is heated to a high temperature, while a driver at the opposite end of the chamber is maintained at a relatively low temperature. The cold end of the chamber is constructed so it can be telescoped to vary the length (L sub 1) of the cold end portion and therefore of the entire chamber, so that the chamber remains resonant to a normal mode frequency, and so that the pressure at the hot end of the chamber is maximized. The precise length of the chamber at any given time, is maintained at an optimum resonant length by a feedback loop. The feedback loop includes an acoustic pressure sensor at the hot end of the chamber, which delivers its output to a control circuit which controls a motor that varies the length (L) of the chamber to a level where the sensed acoustic pressure is a maximum.

  20. 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.

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

    PubMed Central

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

    2013-01-01

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

  2. Open-loop (feed-forward) and feedback control of coronary blood flow during exercise, cardiac pacing, and pressure changes.

    PubMed

    Pradhan, Ranjan K; Feigl, Eric O; Gorman, Mark W; Brengelmann, George L; Beard, Daniel A

    2016-06-01

    A control system model was developed to analyze data on in vivo coronary blood flow regulation and to probe how different mechanisms work together to control coronary flow from rest to exercise, and under a variety of experimental conditions, including cardiac pacing and with changes in coronary arterial pressure (autoregulation). In the model coronary flow is determined by the combined action of a feedback pathway signal that is determined by the level of plasma ATP in coronary venous blood, an adrenergic open-loop (feed-forward) signal that increases with exercise, and a contribution of pressure-mediated myogenic control. The model was identified based on data from exercise experiments where myocardial oxygen extraction, coronary flow, cardiac interstitial norepinephrine concentration, and arterial and coronary venous plasma ATP concentrations were measured during control and during adrenergic and purinergic receptor blockade conditions. The identified model was used to quantify the relative contributions of open-loop and feedback pathways and to illustrate the degree of redundancy in the control of coronary flow. The results indicate that the adrenergic open-loop control component is responsible for most of the increase in coronary blood flow that occurs during high levels of exercise. However, the adenine nucleotide-mediated metabolic feedback control component is essential. The model was evaluated by predicting coronary flow in cardiac pacing and autoregulation experiments with reasonable fits to the data. The analysis shows that a model in which coronary venous plasma adenine nucleotides are a signal in local metabolic feedback control of coronary flow is consistent with the available data.

  3. Closing the Feedback Loop: An Interactive Voice Response System to Provide Follow-up and Feedback in Primary Care Settings

    PubMed Central

    Willig, James H.; Krawitz, Marc; Panjamapirom, Anantachai; Ray, Midge N.; Nevin, Christa R.; English, Thomas M.; Cohen, Mark P.; Berner, Eta S.

    2013-01-01

    In primary care settings, follow-up regarding the outcome of acute outpatient visits is largely absent. We sought to develop an automated interactive voice response system (IVRS) for patient follow-up with feedback to providers capable of interfacing with multiple pre-existing electronic medical records (EMRs). A system was designed to extract data from EMRs, integrate with the IVRS, call patients for follow-up, and provide a feedback report to providers. Challenges during the development process were analyzed and summarized. The components of the technological solution and details of its implementation are reported. Lessons learned include: (1) Modular utilization of system components is often needed to adapt to specific clinic workflow and patient population needs (2) Understanding the local telephony environment greatly impacts development and is critical to success, and (3) Ample time for development of the IVRS questionnaire (mapping all branching paths) and speech recognition tuning (sensitivity, use of barge-in tuning, use of “known voice”) is needed. With proper attention to design and development, modular follow-up and feedback systems can be integrated into existing EMR systems providing the benefits of IVRS follow-up to patients and providers across diverse practice settings. PMID:23340825

  4. Osteoclasts and CD8 T cells form a negative feedback loop that contributes to homeostasis of both the skeletal and immune systems.

    PubMed

    Buchwald, Zachary S; Aurora, Rajeev

    2013-01-01

    There are a number of dynamic regulatory loops that maintain homeostasis of the immune and skeletal systems. In this review, we highlight a number of these regulatory interactions that contribute to maintaining homeostasis. In addition, we review data on a negative regulatory feedback loop between osteoclasts and CD8 T cells that contributes to homeostasis of both the skeletal and immune systems.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-18

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

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

    PubMed Central

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

    2014-01-01

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

  8. Acoustic Beam Forming Array Using Feedback-Controlled Microphones for Tuning and Self-Matching of Frequency Response

    NASA Technical Reports Server (NTRS)

    Radcliffe, Eliott (Inventor); Naguib, Ahmed (Inventor); Humphreys, Jr., William M. (Inventor)

    2014-01-01

    A feedback-controlled microphone includes a microphone body and a membrane operatively connected to the body. The membrane is configured to be initially deflected by acoustic pressure such that the initial deflection is characterized by a frequency response. The microphone also includes a sensor configured to detect the frequency response of the initial deflection and generate an output voltage indicative thereof. The microphone additionally includes a compensator in electric communication with the sensor and configured to establish a regulated voltage in response to the output voltage. Furthermore, the microphone includes an actuator in electric communication with the compensator, wherein the actuator is configured to secondarily deflect the membrane in opposition to the initial deflection such that the frequency response is adjusted. An acoustic beam forming microphone array including a plurality of the above feedback-controlled microphones is also disclosed.

  9. Modeling Attitude Variance in Small UAS’s for Acoustic Signature Simplification Using Experimental Design in a Hardware-in-the-Loop Simulation

    DTIC Science & Technology

    2015-03-26

    MODELING ATTITUDE VARIANCE IN SMALL UAS’S FOR ACOUSTIC SIGNATURE SIMPLIFICATION USING EXPERIMENTAL...and is not subject to copyright protection in the United States. AFIT-ENS-MS-15-M-110 MODELING ATTITUDE VARIANCE IN SMALL UAS’S FOR ACOUSTIC ...IN SMALL UAS’S FOR ACOUSTIC SIGNATURE SIMPLIFICATION USING EXPERIMENTAL DESIGN IN A HARDWARE-IN-THE-LOOP SIMULATION Mitchell N. Gillespie

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. Performance comparisons between passive-phase conjugation and decision-feedback equalizer for underwater acoustic communications

    NASA Astrophysics Data System (ADS)

    Yang, T. C.

    2004-05-01

    Passive-phase conjugation (PPC) uses passive time reversal to remove intersymbol interferences (ISI) for acoustic communications in a multipath environment. It is based on the theory of signal propagation in a waveguide, which says that the Green function (or the impulse response function) convolved with its time-reversed conjugate, summed over a large aperture vertical array of receivers is a delta function in space and time. A decision feedback equalizer (DFE) uses a nonlinear filter to remove ISI based on the minimum mean square errors (MSE) between the estimated and the true (or decision) symbols. These two approaches are motivated by different principles. In this paper, we analyze both using a common framework, illustrating the commonality and differences, pro and con between the two methods, and compare their performances in realistic ocean environments. The performance measures are MSE, output signal-to-noise ratio and bit error rate (BER) as a function of the number of receivers. For a small number of receivers, DFE outperforms PPC in all measures. As the number of receivers increases the BER for both processors approaches zero, but at a different rate. The results are supported by both simulated and real data. [Work supported by ONR.

  12. L/superscript-p/ stability /p ranging from 1 to infinity/ of multivariable non-linear time-varying feedback systems that are open-loop unstable

    NASA Technical Reports Server (NTRS)

    Callier, F. M.; Desoer, C. A.

    1974-01-01

    The loop transformation technique (Sandberg, 1965; Zames, 1966, Willems, 1971), and the fixed point theorem (Schwartz, 1970) are used to derive the L(superscript-p) stability for a class of multivariable nonlinear time-varying feedback systems which are open-loop unstable. The application of the fixed point theorem in L(superscript-p) shows that the nonlinear feedback system has one and only one solution for any pair of inputs in L(superscript-p), that the solutions are continuously dependent on the inputs, and that the closed loop system is L(superscript-p)-stable for any p ranging from 1 to infinity.

  13. 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.

  14. Electro-optic chaotic system based on the reverse-time chaos theory and a nonlinear hybrid feedback loop.

    PubMed

    Jiang, Xingxing; Cheng, Mengfan; Luo, Fengguang; Deng, Lei; Fu, Songnian; Ke, Changjian; Zhang, Minming; Tang, Ming; Shum, Ping; Liu, Deming

    2016-12-12

    A novel electro-optic chaos source is proposed on the basis of the reverse-time chaos theory and an analog-digital hybrid feedback loop. The analog output of the system can be determined by the numeric states of shift registers, which makes the system robust and easy to control. The dynamical properties as well as the complexity dependence on the feedback parameters are investigated in detail. The correlation characteristics of the system are also studied. Two improving strategies which were established in digital field and analog field are proposed to conceal the time-delay signature. The proposed scheme has the potential to be used in radar and optical secure communication systems.

  15. Epidermal identity is maintained by cell-cell communication via a universally active feedback loop in Arabidopsis thaliana.

    PubMed

    San-Bento, Rita; Farcot, Etienne; Galletti, Roberta; Creff, Audrey; Ingram, Gwyneth

    2014-01-01

    The transcription factors ARABIDOPSIS THALIANA MERISTEM L1 (ATML1) and PROTODERMAL FACTOR2 (PDF2) are indispensable for epidermal cell-fate specification in Arabidopsis embryos. However, the mechanisms of regulation of these genes, particularly their relationship with cell-cell signalling pathways, although the subject of considerable speculation, remain unclear. Here we demonstrate that the receptor kinase ARABIDOPSIS CRINKLY4 (ACR4) positively affects the expression of ATML1 and PDF2 in seedlings. In contrast, ATML1- and PDF2-containing complexes directly and negatively affect both their own expression and that of ACR4. By modelling the resulting feedback loop, we demonstrate a network structure that is capable of maintaining robust epidermal cell identity post-germination. We show that a second seed-specific signalling pathway involving the subtilase ABNORMAL LEAFSHAPE1 (ALE1) and the receptor kinases GASSHO1 (GSO1) and GASSHO2 (GSO2) acts in parallel to the epidermal loop to control embryonic surface formation via an ATML1/PDF2-independent pathway. Genetic interactions between components of this linear pathway and the epidermal loop suggest that an intact embryo surface is necessary for initiation and/or stabilization of the epidermal loop, specifically during early embryogenesis.

  16. Novel feedback loop between M2 macrophages/microglia and regulatory B cells in estrogen-protected EAE mice.

    PubMed

    Benedek, Gil; Zhang, Jun; Nguyen, Ha; Kent, Gail; Seifert, Hilary; Vandenbark, Arthur A; Offner, Halina

    2017-04-15

    Immunoregulatory sex hormones, including estrogen and estriol, may prevent relapses in multiple sclerosis during pregnancy. Our previous studies have demonstrated that regulatory B cells are crucial for estrogen-mediated protection against experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate an estrogen-dependent induction of alternatively activated (M2) macrophages/microglia that results in an increased frequency of regulatory B cells in the spinal cord of estrogen treated mice with EAE. We further demonstrate that cultured M2-polarized microglia promote the induction of regulatory B cells. Our study suggests that estrogen neuroprotection induces a regulatory feedback loop between M2 macrophages/microglia and regulatory B cells.

  17. All-optical flip-flop based on an active Mach Zehnder interferometer with a feedback loop

    NASA Astrophysics Data System (ADS)

    Clavero, R.; Ramos, F.; Martí, J.

    2005-11-01

    A novel architecture for an all-optical flip-flop is validated experimentally. The architecture comprises a single semiconductor optical amplifier based Mach Zehnder interferometer with an external feedback loop. The experimental results show optical bistable operation for a latching device with an on off contrast ratio of 11 dB that employs set and reset pulses of less than 250 pJ, although the energy of these pulses could be greatly reduced by optical integration of the whole device.

  18. 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.

  19. miR-285-Yki/Mask double-negative feedback loop mediates blood-brain barrier integrity in Drosophila.

    PubMed

    Li, Dong; Liu, Yanling; Pei, Chunli; Zhang, Peng; Pan, Linqing; Xiao, Jing; Meng, Songshu; Yuan, Zengqiang; Bi, Xiaolin

    2017-03-21

    The Hippo signaling pathway is highly conserved from Drosophila to mammals and plays a central role in maintaining organ size and tissue homeostasis. The blood-brain barrier (BBB) physiologically isolates the brain from circulating blood or the hemolymph system, and its integrity is strictly maintained to perform sophisticated neuronal functions. Until now, the underlying mechanisms of subperineurial glia (SPG) growth and BBB maintenance during development are not clear. Here, we report an miR-285-Yorkie (Yki)/Multiple Ankyrin repeats Single KH domain (Mask) double-negative feedback loop that regulates SPG growth and BBB integrity. Flies with a loss of miR-285 have a defective BBB with increased SPG ploidy and disruptive septate junctions. Mechanistically, miR-285 directly targets the Yki cofactor Mask to suppress Yki activity and down-regulates the expression of its downstream target cyclin E, a key regulator of cell cycle. Disturbance of cyclin E expression in SPG causes abnormal endoreplication, which leads to aberrant DNA ploidy and defective septate junctions. Moreover, the expression of miR-285 is increased by knockdown of yki or mask and is decreased with yki overexpression, thus forming a double-negative feedback loop. This regulatory loop is crucial for sustaining an appropriate Yki/Mask activity and cyclin E level to maintain SPG ploidy and BBB integrity. Perturbation of this signaling loop, either by dysregulated miR-285 expression or Yki activity, causes irregular SPG ploidy and BBB disruption. Furthermore, ectopic expression of miR-285 promotes canonical Hippo pathway-mediated apoptosis independent of the p53 or JNK pathway. Collectively, these results reveal an exquisite regulatory mechanism for BBB maintenance through an miR-285-Yki/Mask regulatory circuit.

  20. 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.

  1. 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.

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

    PubMed

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

    2015-01-01

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

  3. Closed-loop fiber-optic gyroscope with a sawtooth phase-modulated feedback.

    PubMed

    Ebberg, A; Schiffner, G

    1985-06-01

    Theoretical and experimental investigations of a closed-loop fiber-optic gyroscope are reported. Phase nulling is accomplished by applying a sawtooth modulation to an integrated-optic phase modulator located at one side of the sensing loop. The frequency of the phase modulation is proportional to the rotation rate, thus permitting a digital readout. The influence of a finite flyback period on the scale factor is investigated.

  4. 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.

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

    PubMed Central

    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.

    2015-01-01

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

  6. 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.

  7. Multiple feedback loop design in the tryptophan regulatory network of Escherichia coli suggests a paradigm for robust regulation of processes in series

    PubMed Central

    Bhartiya, Sharad; Chaudhary, Nikhil; Venkatesh, K.V; Doyle, Francis J

    2005-01-01

    Biological networks have evolved through adaptation in uncertain environments. Of the different possible design paradigms, some may offer functional advantages over others. These designs can be quantified by the structure of the network resulting from molecular interactions and the parameter values. One may, therefore, like to identify the design motif present in the evolved network that makes it preferable over other alternatives. In this work, we focus on the regulatory networks characterized by serially arranged processes, which are regulated by multiple feedback loops. Specifically, we consider the tryptophan system present in Escherichia coli, which may be conceptualized as three processes in series, namely transcription, translation and tryptophan synthesis. The multiple feedback loop motif results from three distinct negative feedback loops, namely genetic repression, mRNA attenuation and enzyme inhibition. A framework is introduced to identify the key design components of this network responsible for its physiological performance. We demonstrate that the multiple feedback loop motif, as seen in the tryptophan system, enables robust performance to variations in system parameters while maintaining a rapid response to achieve homeostasis. Superior performance, if arising from a design principle, is intrinsic and, therefore, inherent to any similarly designed system, either natural or engineered. An experimental engineering implementation of the multiple feedback loop design on a two-tank system supports the generality of the robust attributes offered by the design. PMID:16849267

  8. The inflammatory/cancer-related IL-6/STAT3/NF-κB positive feedback loop includes AUF1 and maintains the active state of breast myofibroblasts

    PubMed Central

    Hendrayani, Siti-Fauziah; Al-Harbi, Bothaina; Al-Ansari, Mysoon M.; Silva, Gabriela; Aboussekhra, Abdelilah

    2016-01-01

    The IL-6/STAT3/NF-κB positive feedback loop links inflammation to cancer and maintains cells at a transformed state. Similarly, cancer-associated myofibroblats remains active even in absence of cancer cells. However, the molecular basis of this sustained active state remains elusive. We have shown here that breast cancer cells and IL-6 persistently activate breast stromal fibroblasts through the stimulation of the positive IL-6/STAT3/NF-κB feedback loop. Transient neutralization of IL-6 in culture inhibited this signaling circuit and reverted myofibrobalsts to a normalized state, suggesting the implication of the IL-6 autocrine feedback loop as well. Importantly, the IL-6/STAT3/NF-κB pro-inflammatory circuit was also active in cancer-associated fibroblasts isolated from breast cancer patients. Transient inhibition of STAT3 by specific siRNA in active fibroblasts persistently reduced the level of the RNA binding protein AUF1, blocked the loop and normalized these cells. Moreover, we present clear evidence that AUF1 is also part of this positive feedback loop. Interestingly, treatment of breast myofibroblasts with caffeine, which has been previously shown to persistently inhibit active breast stromal fibroblasts, blocked the positive feedback loop through potent and sustained inhibition of STAT3, AKT, lin28B and AUF1. These results indicate that the IL-6/STAT3/NF-κB positive feedback loop includes AUF1 and is responsible for the sustained active status of cancer-associated fibroblasts. We have also shown that normalizing myofibroblasts, which could be of great therapeutic value, is possible through the inhibition of this procarcinogenic circuit. PMID:27248826

  9. Gain drift compensation with no-feedback-loop developed for the X-IFU/ATHENA readout chain

    NASA Astrophysics Data System (ADS)

    Prêle, D.; Voisin, F.; Beillimaz, C.; Chen, S.; Goldwurm, A.

    2016-07-01

    The focal plane of the X-ray Integral Field Unit (X-IFU) instrument of the Athena observatory is composed of about 4000 micro-calorimeters. These sensors, based on superconducting Transition Edge Sensors, are read out through a frequency multiplexer and a base-band feedback to linearize SQUIDs. However, the loop gain of this feedback is lower than 10 in the modulated TES signal bandwidth, which is not enough to fix the gain of the full readout chain. Calibration of the instrument is planned to be done at a time scale larger than a dozen minutes and the challenging energy resolution goal of 2.5 eV at 6 keV will probably require a gain stability larger than 10-4 over a long duration. A large part of this gain is provided by a Low-Noise Amplifier (LNA) in the Warm Front-End Electronics (WFEE). To reach such gain stability over more than a dozen minutes, this non-cooled amplifier has to cope with the temperature and supply voltage variations. Moreover, mainly for noise reasons, common large loop gain with feedback can not be used. We propose a new amplifier topology using diodes as loads of a differential amplifier to provide a fixed voltage gain, independent of the temperature and of the bias fluctuations. This amplifier is designed using a 350 nm SiGe BiCMOS technology and is part of an integrated circuit developed for the WFEE. Our simulations provide the expected gain drift and noise performances of such structure. Comparison with standard resistive loaded differential pair clearly shows the advantages of the proposed amplifier topology with a gain drift decreasing by more than an order of magnitude. Performances of this diode loaded amplifier are discussed in the context of the X-IFU requirements.

  10. 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

  11. 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.

  12. Predictability is necessary for closed-loop visual feedback delay adaptation.

    PubMed

    Rohde, Marieke; van Dam, Loes C J; Ernst, Marc O

    2014-03-05

    In case of delayed visual feedback during visuomotor tasks, like in some sluggish computer games, humans can modulate their behavior to compensate for the delay. However, opinions on the nature of this compensation diverge. Some studies suggest that humans adapt to feedback delays with lasting changes in motor behavior (aftereffects) and a recalibration of time perception. Other studies have shown little or no evidence for such semipermanent recalibration in the temporal domain. We hypothesize that predictability of the reference signal (target to be tracked) is necessary for semipermanent delay adaptation. To test this hypothesis, we trained participants with a 200 ms visual feedback delay in a visually guided manual tracking task, varying the predictability of the reference signal between conditions, but keeping reference motion and feedback delay constant. In Experiment 1, we focused on motor behavior. Only training in the predictable condition brings about all of the adaptive changes and aftereffects expected from delay adaptation. In Experiment 2, we used a synchronization task to investigate perceived simultaneity (perceptuomotor learning). Supporting the hypothesis, participants recalibrated subjective visuomotor simultaneity only when trained in the predictable condition. Such a shift in perceived simultaneity was also observed in Experiment 3, using an interval estimation task. These results show that delay adaptation in motor control can modulate the perceived temporal alignment of vision and kinesthetically sensed movement. The coadaptation of motor prediction and target prediction (reference extrapolation) seems necessary for such genuine delay adaptation. This offers an explanation for divergent results in the literature.

  13. 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…

  14. 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.

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

    DOEpatents

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

    1992-11-24

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

  16. 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.

  17. Theoretical study of a thermo-acousto-electric generator equipped with an electroacoustic feedback loop

    NASA Astrophysics Data System (ADS)

    Olivier, Come; Penelet, Guillaume; Poignand, Gaelle; Lotton, Pierrick

    2015-10-01

    A simplified model of a Stirling-type thermoacoustic engine coupled to a resonant mechanical system is presented. The acoustic network is presented as its temperature-dependent lumped element equivalent, and the nonlinear effects involved in such engines are accounted for in a nonlinear heat equation governing the temperature distribution through the thermoacoustic core. The low-order model is sufficient to capture the behavior of the engine, both in terms of stability and dynamic behavior.

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

    PubMed

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

    2016-02-01

    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-STAT3(Y705) 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.

  19. 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.

  20. A PDE-based methodology for modeling, parameter estimation and feedback control in structural and structural acoustic systems

    NASA Technical Reports Server (NTRS)

    Banks, H. T.; Brown, D. E.; Metcalf, Vern L.; Silcox, R. J.; Smith, Ralph C.; Wang, Yun

    1994-01-01

    A problem of continued interest concerns the control of vibrations in a flexible structure and the related problem of reducing structure-borne noise in structural acoustic systems. In both cases, piezoceramic patches bonded to the structures have been successfully used as control actuators. Through the application of a controlling voltage, the patches can be used to reduce structural vibrations which in turn lead to methods for reducing structure-borne noise. A PDE-based methodology for modeling, estimating physical parameters, and implementing a feedback control scheme for problems of this type is discussed. While the illustrating example is a circular plate, the methodology is sufficiently general so as to be applicable in a variety of structural and structural acoustic systems.

  1. A dynamic feedback control strategy for control loops with time-varying delay

    NASA Astrophysics Data System (ADS)

    Ebrahimi, Behrouz; Tafreshi, Reza; Franchek, Matthew; Grigoriadis, Karolos; Mohammadpour, Javad

    2014-05-01

    Dynamic systems of nth order with time-varying delay in the control loop are examined in this paper. The infinite-dimensional pure delay problem is approximated using a jth-order Padé approximation. Although the approximation provides a well-matched finite-dimensional configuration, it poses a new challenge in terms of unstable internal dynamics for the resulted non-minimum phase system. Such a non-minimum phase characteristic limits the closed-loop system bandwidth and leads to an imperfect tracking performance. To circumvent this problem, the unstable internal dynamics of the system is captured and a new dynamic compensator is proposed to stabilise it in a systematic framework. A dynamic controller is developed, which provides the overall system stability against unmatched perturbation and meets the desired tracking error dynamics. The proposed approach is then applied to fuelling control in gasoline engines addressing the varying transport delay of the oxygen-sensor measurement in the exhaust. The developed methodology is finally validated on a Ford F-150 SI lean-burn engine model with large time-varying delay in the control loop.

  2. A closed-loop automatic control system for high-intensity acoustic test systems.

    NASA Technical Reports Server (NTRS)

    Slusser, R. A.

    1973-01-01

    Sound at sound pressure levels in the range from 130 to 160 dB is used in the investigation. Random noise is passed through a series of parallel filters, generally 1/3-octave wide. A basic automatic system is investigated because of preadjustment inaccuracies and high costs found in a study of a typical manually controlled acoustic testing system. The unit described has been successfully used in automatic acoustic tests in connection with the spacecraft tests for the Mariner 1971 program.

  3. Passive mode locking and formation of dissipative solitons in electron oscillators with a bleaching absorber in the feedback loop

    NASA Astrophysics Data System (ADS)

    Ginzburg, N. S.; Kocharovskaya, E. R.; Vilkov, M. N.; Sergeev, A. S.

    2017-01-01

    The mechanisms of passive mode locking and formation of ultrashort pulses in microwave electron oscillators with a bleaching absorber in the feedback loop have been analyzed. It is shown that in the group synchronism regime in which the translational velocity of particles coincides with the group velocity of the electromagnetic wave, the pulse formation can be described by the equations known in the theory of dissipative solitons. At the same time, the regimes in which the translational velocity of electrons differs from the group velocity and the soliton being formed and moving along the electron beam consecutively (cumulatively) receives energy from various electron fractions are optimal for generating pulses with the maximal peak amplitudes.

  4. 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

  5. Shaping meiotic chromosomes with SUMO: a feedback loop controls the assembly of the synaptonemal complex in budding yeast

    PubMed Central

    Tsubouchi, Hideo; Argunhan, Bilge; Tsubouchi, Tomomi

    2016-01-01

    The synaptonemal complex (SC) is a meiosis-specific chromosomal structure in which homologous chromosomes are intimately linked through arrays of specialized proteins called transverse filaments (TF). Widely conserved in eukaryote meiosis, the SC forms during prophase I and is essential for accurate segregation of homologous chromosomes at meiosis I. However, the basic mechanism overlooking formation and regulation of the SC has been poorly understood. By using the budding yeast Saccharomyces cerevisiae, we recently showed that SC formation is controlled through the attachment of multiple molecules of small ubiquitin-like modifier (SUMO) to a regulator of TF assembly. Intriguingly, this SUMOylation is activated by TF, implicating the involvement of a positive feedback loop in the control of SC assembly. We discuss the implication of this finding and possible involvement of a similar mechanism in regulating other processes.

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

    PubMed

    Farcot, Etienne; Gouzé, Jean-Luc

    2009-12-01

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

  7. 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

  8. 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

  9. A regulatory feedback loop involving p63 and IRF6 links the pathogenesis of 2 genetically different human ectodermal dysplasias.

    PubMed

    Moretti, Francesca; Marinari, Barbara; Lo Iacono, Nadia; Botti, Elisabetta; Giunta, Alessandro; Spallone, Giulia; Garaffo, Giulia; Vernersson-Lindahl, Emma; Merlo, Giorgio; Mills, Alea A; Ballarò, Costanza; Alemà, Stefano; Chimenti, Sergio; Guerrini, Luisa; Costanzo, Antonio

    2010-05-01

    The human congenital syndromes ectrodactyly ectodermal dysplasia-cleft lip/palate syndrome, ankyloblepharon ectodermal dysplasia clefting, and split-hand/foot malformation are all characterized by ectodermal dysplasia, limb malformations, and cleft lip/palate. These phenotypic features are a result of an imbalance between the proliferation and differentiation of precursor cells during development of ectoderm-derived structures. Mutations in the p63 and interferon regulatory factor 6 (IRF6) genes have been found in human patients with these syndromes, consistent with phenotypes. Here, we used human and mouse primary keratinocytes and mouse models to investigate the role of p63 and IRF6 in proliferation and differentiation. We report that the DeltaNp63 isoform of p63 activated transcription of IRF6, and this, in turn, induced proteasome-mediated DeltaNp63 degradation. This feedback regulatory loop allowed keratinocytes to exit the cell cycle, thereby limiting their ability to proliferate. Importantly, mutations in either p63 or IRF6 resulted in disruption of this regulatory loop: p63 mutations causing ectodermal dysplasias were unable to activate IRF6 transcription, and mice with mutated or null p63 showed reduced Irf6 expression in their palate and ectoderm. These results identify what we believe to be a novel mechanism that regulates the proliferation-differentiation balance of keratinocytes essential for palate fusion and skin differentiation and links the pathogenesis of 2 genetically different groups of ectodermal dysplasia syndromes into a common molecular pathway.

  10. 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.

  11. A Negative Feedback Loop between PHYTOCHROME INTERACTING FACTORs and HECATE Proteins Fine-Tunes Photomorphogenesis in Arabidopsis

    PubMed Central

    Zhu, Ling; Bu, Qingyun; Shen, Hui; Dang, Jonathan

    2016-01-01

    The phytochrome interacting factors (PIFs), a small group of basic helix-loop-helix transcription factors, repress photomorphogenesis both in the dark and light. Light signals perceived by the phytochrome family of photoreceptors induce rapid degradation of PIFs to promote photomorphogenesis. Here, we show that HECATE (HEC) proteins, another small group of HLH proteins, antagonistically regulate PIFs to promote photomorphogenesis. HEC1 and HEC2 heterodimerize with PIF family members. PIF1, HEC1, and HEC2 genes are spatially and temporally coexpressed, and HEC2 is localized in the nucleus. hec1, hec2, and hec3 single mutants and the hec1 hec2 double mutant showed hyposensitivity to light-induced seed germination and accumulation of chlorophyll and carotenoids, hallmark processes oppositely regulated by PIF1. HEC2 inhibits PIF1 target gene expression by directly heterodimerizing with PIF1 and preventing DNA binding and transcriptional activation activity of PIF1. Conversely, PIFs directly activate the expression of HEC1 and HEC2 in the dark, and light reduces the expression of these HECs possibly by degrading PIFs. HEC2 is partially degraded in the dark through the ubiquitin/26S-proteasome pathway and is stabilized by light. HEC2 overexpression also reduces the light-induced degradation of PIF1. Taken together, these data suggest that PIFs and HECs constitute a negative feedback loop to fine-tune photomorphogenesis in Arabidopsis thaliana. PMID:27073231

  12. An Nkx2-5/Bmp2/Smad1 negative feedback loop controls second heart field progenitor specification and proliferation

    PubMed Central

    Prall, Owen WJ; Menon, Mary K; Solloway, Mark J; Watanabe, Yusuke; Zaffran, Stéphane; Bajolle, Fanny; Biben, Christine; McBride, Jim J; Robertson, Bronwyn R; Chaulet, Hervé; Stennard, Fiona A; Wise, Natalie; Schaft, Daniel; Wolstein, Orit; Furtado, Milena B; Shiratori, Hidetaka; Chien, Kenneth R; Hamada, Hiroshi; Black, Brian L; Saga, Yumiko; Robertson, Elizabeth J; Buckingham, Margaret E; Harvey, Richard P

    2007-01-01

    Summary During heart development the second heart field (SHF) provides progenitor cells for most cardiomyocytes and expresses the homeodomain factor Nkx2-5. We now show that feedback repression of Bmp2/Smad1 signaling by Nkx2-5 critically regulates SHF proliferation and outflow tract (OFT) morphology. In the cardiac fields of Nkx2-5 mutants, genes controlling cardiac specification (including Bmp2) and maintenance of the progenitor state were up-regulated, leading initially to progenitor over-specification, but subsequently to failed SHF proliferation and OFT truncation. In Smad1 mutants, SHF proliferation and deployment to the OFT were increased, while Smad1 deletion in Nkx2-5 mutants rescued SHF proliferation and OFT development. In Nkx2-5 hypomorphic mice, which recapitulate human congenital heart disease (CHD), OFT anomalies were also rescued by Smad1 deletion. Our findings demonstrate that Nkx2-5 orchestrates the transition between periods of cardiac induction, progenitor proliferation and OFT morphogenesis via a Smad1-dependent negative feedback loop, which may be a frequent molecular target in CHD. PMID:17350578

  13. Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis.

    PubMed

    Li, Hai-Yan; Ju, Di; Zhang, Da-Wei; Li, Hao; Kong, Ling-Min; Guo, Yanhai; Li, Can; Wang, Xi-Long; Chen, Zhi-Nan; Bian, Huijie

    2015-11-12

    Activation of hepatic stellate cells (HSCs) by transforming growth factor-β1 (TGF-β1) initiates HBV-associated fibrogenesis. The mechanism of TGF-β1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-β1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-β1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-β1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-β1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-β1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-β1 synthesis. These findings indicate that TGF-β1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-β receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis.

  14. 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.

  15. Multiple feedback loops through cytokinin signaling control stem cell number within the Arabidopsis shoot meristem.

    PubMed

    Gordon, Sean P; Chickarmane, Vijay S; Ohno, Carolyn; Meyerowitz, Elliot M

    2009-09-22

    A central unanswered question in stem cell biology, both in plants and in animals, is how the spatial organization of stem cell niches are maintained as cells move through them. We address this question for the shoot apical meristem (SAM) which harbors pluripotent stem cells responsible for growth of above-ground tissues in flowering plants. We find that localized perception of the plant hormone cytokinin establishes a spatial domain in which cell fate is respecified through induction of the master regulator WUSCHEL as cells are displaced during growth. Cytokinin-induced WUSCHEL expression occurs through both CLAVATA-dependent and CLAVATA-independent pathways. Computational analysis shows that feedback between cytokinin response and genetic regulators predicts their relative patterning, which we confirm experimentally. Our results also may explain how increasing cytokinin concentration leads to the first steps in reestablishing the shoot stem cell niche in vitro.

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

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

  17. Effect of positive feedback loops on the robustness of oscillations in the network of cyclin-dependent kinases driving the mammalian cell cycle.

    PubMed

    Gérard, Claude; Gonze, Didier; Goldbeter, Albert

    2012-09-01

    The transitions between the G(1), S, G(2) and M phases of the mammalian cell cycle are driven by a network of cyclin-dependent kinases (Cdks), whose sequential activation is regulated by intertwined negative and positive feedback loops. We previously proposed a detailed computational model for the Cdk network, and showed that this network is capable of temporal self-organization in the form of sustained oscillations, which govern ordered progression through the successive phases of the cell cycle [Gérard and Goldbeter (2009) Proc Natl Acad Sci USA 106, 21643-21648]. We subsequently proposed a skeleton model for the cell cycle that retains the core regulatory mechanisms of the detailed model [Gérard and Goldbeter (2011) Interface Focus 1, 24-35]. Here we extend this skeleton model by incorporating Cdk regulation through phosphorylation/dephosphorylation and by including the positive feedback loops that underlie the dynamics of the G(1)/S and G(2)/M transitions via phosphatase Cdc25 and via phosphatase Cdc25 and kinase Wee1, respectively. We determine the effects of these positive feedback loops and ultrasensitivity in phosphorylation/dephosphorylation on the dynamics of the Cdk network. The multiplicity of positive feedback loops as well as the existence of ultrasensitivity promote the occurrence of bistability and increase the amplitude of the oscillations in the various cyclin/Cdk complexes. By resorting to stochastic simulations, we further show that the presence of multiple, redundant positive feedback loops in the G(2)/M transition of the cell cycle markedly enhances the robustness of the Cdk oscillations with respect to molecular noise.

  18. Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer.

    PubMed

    Kuo, Kung-Kai; Lee, King-Teh; Chen, Ker-Kong; Yang, Ya-Han; Lin, Ying-Chu; Tsai, Ming-Ho; Wuputra, Kenly; Lee, Yen-Liang; Ku, Chia-Chen; Miyoshi, Hiroyuki; Nakamura, Yukio; Saito, Shigeo; Wu, Chun-Chieh; Chai, Chee-Yin; Eckner, Richard; Steve Lin, Chen-Lung; Wang, Sophie S-W; Wu, Deng-Chyang; Lin, Chang-Shen; Yokoyama, Kazunari K

    2016-06-24

    The network of stemness genes and oncogenes in human patient-specific reprogrammed cancer stem cells (CSCs) remains elusive, especially in liver cancer. HepG2-derived induced pluripotent stem cell-like cells (HepG2-iPS-like cells) were generated by introducing Yamanaka factors and the knockdown vector shTP53. They exhibited features of stemness and a higher tumorigenesis after xenograft transplantation compared with HepG2 cells. The cancerous mass of severe combined immunodeficiency (SCID) mice derived from one colony was dissected and cultured to establish reprogrammed HepG2-derived CSC-like cells (designated rG2-DC-1C). A single colony exhibited 42% occurrence of tumors with higher proliferation capacities. rG2-DC-1C showed continuous expression of the OCT4 stemness gene and of representative tumor markers, potentiated chemoresistance characteristics, and invasion activities. The sphere-colony formation ability and the invasion activity of rG2-DC-1C were also higher than those of HepG2 cells. Moreover, the expression of the OCT4 gene and the c-JUN oncogene, but not of c-MYC, was significantly elevated in rG2-DC-1C, whereas no c-JUN expression was observed in HepG2 cells. The positive-feedback regulation via OCT4-mediated transactivation of the c-JUN promoter and the c-JUN-mediated transactivation of the OCT4 promoter were crucial for promoting cancer development and maintaining cancer stemness in rG2-DC-1C. Increased expression of OCT4 and c-JUN was detected in the early stage of human liver cancer. Therefore, the positive feedback regulation of OCT4 and c-JUN, resulting in the continuous expression of oncogenes such as c-JUN, seems to play a critical role in the determination of the cell fate decision from iPS cells to CSCs in liver cancer. Stem Cells 2016.

  19. 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

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

    PubMed Central

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

    2013-01-01

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

  1. In vivo Microscale Measurements of Light and Photosynthesis during Coral Bleaching: Evidence for the Optical Feedback Loop?

    PubMed

    Wangpraseurt, Daniel; Holm, Jacob B; Larkum, Anthony W D; Pernice, Mathieu; Ralph, Peter J; Suggett, David J; Kühl, Michael

    2017-01-01

    Climate change-related coral bleaching, i.e., the visible loss of zooxanthellae from the coral host, is increasing in frequency and extent and presents a major threat to coral reefs globally. Coral bleaching has been proposed to involve accelerating light stress of their microalgal endosymbionts via a positive feedback loop of photodamage, symbiont expulsion and excess in vivo light exposure. To test this hypothesis, we used light and O2 microsensors to characterize in vivo light exposure and photosynthesis of Symbiodinium during a thermal stress experiment. We created tissue areas with different densities of Symbiodinium cells in order to understand the optical properties and light microenvironment of corals during bleaching. Our results showed that in bleached Pocillopora damicornis corals, Symbiodinium light exposure was up to fivefold enhanced relative to healthy corals, and the relationship between symbiont loss and light enhancement was well-described by a power-law function. Cell-specific rates of Symbiodinium gross photosynthesis and light respiration were enhanced in bleached P. damicornis compared to healthy corals, while areal rates of net photosynthesis decreased. Symbiodinium light exposure in Favites sp. revealed the presence of low light microniches in bleached coral tissues, suggesting that light scattering in thick coral tissues can enable photoprotection of cryptic symbionts. Our study provides evidence for the acceleration of in vivo light exposure during coral bleaching but this optical feedback mechanism differs between coral hosts. Enhanced photosynthesis in relation to accelerating light exposure shows that coral microscale optics exerts a key role on coral photophysiology and the subsequent degree of radiative stress during coral bleaching.

  2. In vivo Microscale Measurements of Light and Photosynthesis during Coral Bleaching: Evidence for the Optical Feedback Loop?

    PubMed Central

    Wangpraseurt, Daniel; Holm, Jacob B.; Larkum, Anthony W. D.; Pernice, Mathieu; Ralph, Peter J.; Suggett, David J.; Kühl, Michael

    2017-01-01

    Climate change-related coral bleaching, i.e., the visible loss of zooxanthellae from the coral host, is increasing in frequency and extent and presents a major threat to coral reefs globally. Coral bleaching has been proposed to involve accelerating light stress of their microalgal endosymbionts via a positive feedback loop of photodamage, symbiont expulsion and excess in vivo light exposure. To test this hypothesis, we used light and O2 microsensors to characterize in vivo light exposure and photosynthesis of Symbiodinium during a thermal stress experiment. We created tissue areas with different densities of Symbiodinium cells in order to understand the optical properties and light microenvironment of corals during bleaching. Our results showed that in bleached Pocillopora damicornis corals, Symbiodinium light exposure was up to fivefold enhanced relative to healthy corals, and the relationship between symbiont loss and light enhancement was well-described by a power-law function. Cell-specific rates of Symbiodinium gross photosynthesis and light respiration were enhanced in bleached P. damicornis compared to healthy corals, while areal rates of net photosynthesis decreased. Symbiodinium light exposure in Favites sp. revealed the presence of low light microniches in bleached coral tissues, suggesting that light scattering in thick coral tissues can enable photoprotection of cryptic symbionts. Our study provides evidence for the acceleration of in vivo light exposure during coral bleaching but this optical feedback mechanism differs between coral hosts. Enhanced photosynthesis in relation to accelerating light exposure shows that coral microscale optics exerts a key role on coral photophysiology and the subsequent degree of radiative stress during coral bleaching. PMID:28174567

  3. 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

  4. Influence of Acoustic Feedback on the Learning Strategies of Neural Network-Based Sound Classifiers in Digital Hearing Aids

    NASA Astrophysics Data System (ADS)

    Cuadra, Lucas; Alexandre, Enrique; Gil-Pita, Roberto; Vicen-Bueno, Raúl; Álvarez, Lorena

    2009-12-01

    Sound classifiers embedded in digital hearing aids are usually designed by using sound databases that do not include the distortions associated to the feedback that often occurs when these devices have to work at high gain and low gain margin to oscillation. The consequence is that the classifier learns inappropriate sound patterns. In this paper we explore the feasibility of using different sound databases (generated according to 18 configurations of real patients), and a variety of learning strategies for neural networks in the effort of reducing the probability of erroneous classification. The experimental work basically points out that the proposed methods assist the neural network-based classifier in reducing its error probability in more than 18%. This helps enhance the elderly user's comfort: the hearing aid automatically selects, with higher success probability, the program that is best adapted to the changing acoustic environment the user is facing.

  5. Positive feedback loop of IL-1β/Akt/RARα/Akt signaling mediates oncogenic property of RARα in gastric carcinoma

    PubMed Central

    Huang, Gui-Li; Liu, Yu; Shen, Jin-Xing; Zhou, Pan; Liu, Wen-Ming; Shen, Dong-Yan

    2017-01-01

    Abnormal expression and function of retinoic acid receptor α (RARα) have been reported to be associated with various cancers including acute promyelocytic leukemia and hepatocellular carcinoma. However, the role and the mechanism of RARα in gastric carcinoma (GC) were unknown. Here, the expression of RARα was frequently elevated in human GC tissues and cell lines, and its overexpression was closely correlated with tumor size, lymph node metastasis and clinical stages in GC patients. Moreover, RARα overexpression was related with pathological differentiation. Functionally, RARα knockdown inhibited the proliferation and metastasis of GC cells, as well as enhanced drug susceptibility both in vitro and in vivo. Additionally, RARα knockdown suppressed GC progression through regulating the expression of cell proliferation, cell cycle, invasion and drug resistance associated proteins, such as PCNA, CyclinB1, CyclinD2, CyclinE, p21, MMP9 and MDR1. Mechanistically, the above oncogenic properties of RARα in GC were closely associated with Akt signaling activation. Moreover, overexpression of RARα was induced by IL-1β/Akt signaling activation, which suggested a positive feedback loop of IL-1β/Akt/RARα/Akt signaling in GC. Taken together, we demonstrated that RARα was frequently elevated in GC and exerted oncogenic properties. It might be a potential molecular target for GC treatment. PMID:28035062

  6. PPAR{gamma} ligands suppress the feedback loop between E2F2 and cyclin-E1

    SciTech Connect

    Komatsu, Yoko; Ito, Ichiaki; Wayama, Mitsutoshi; Fujimura, Akiko; Akaogi, Kensuke; Machida, Hikaru; Nakajima, Yuka; Kuroda, Takao; Ohmori, Kazuji; Murayama, Akiko; Kimura, Keiji; Yanagisawa, Junn

    2008-05-23

    PPAR{gamma} is a nuclear hormone receptor that plays a key role in the induction of peroxisome proliferation. A number of studies showed that PPAR{gamma} ligands suppress cell cycle progression; however, the mechanism remains to be determined. Here, we showed that PPAR{gamma} ligand troglitazone inhibited G1/S transition in colon cancer cells, LS174T. Troglitazone did not affect on either expression of CDK inhibitor (p18) or Wnt signaling pathway, indicating that these pathways were not involved in the troglitazone-dependent cell cycle arrest. GeneChip and RT-PCR analyses revealed that troglitazone decreased mRNA levels of cell cycle regulatory factors E2F2 and cyclin-E1 whose expression is activated by E2F2. Down-regulation of E2F2 by troglitazone results in decrease of cyclin-E1 transcription, which could inhibit phosphorylation of Rb protein, and consequently evoke the suppression of E2F2 transcriptional activity. Thus, we propose that troglitazone suppresses the feedback loop containing E2F2, cyclin-E1, and Rb protein.

  7. Interaction of apoptotic cells with macrophages upregulates COX-2/PGE2 and HGF expression via a positive feedback loop.

    PubMed

    Byun, Ji Yeon; Youn, Young-So; Lee, Ye-Ji; Choi, Youn-Hee; Woo, So-Yeon; Kang, Jihee Lee

    2014-01-01

    Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and hepatocyte growth factor (HGF) play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2 expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cells in vitro and in vivo orchestrate the interaction between COX-2/PGE2 and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2 production. Both NS-398 and COX-2-siRNA, as well as the PGE2 receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2 induction. The in vivo relevance of the interaction between the COX-2/PGE2 and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages following in vivo exposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE2 and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition.

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

    PubMed

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

    2015-11-03

    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.

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

    PubMed

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

    2015-12-15

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

  10. Cytochrome P450s in human immune cells regulate IL-22 and c-Kit via an AHR feedback loop

    PubMed Central

    Effner, Renate; Hiller, Julia; Eyerich, Stefanie; Traidl-Hoffmann, Claudia; Brockow, Knut; Triggiani, Massimo; Behrendt, Heidrun; Schmidt-Weber, Carsten B.; Buters, Jeroen T. M.

    2017-01-01

    The mechanisms how environmental compounds influence the human immune system are unknown. The environmentally sensitive transcription factor aryl hydrocarbon receptor (AHR) has immune-modulating functions and responds to small molecules. Cytochrome P4501 enzymes (CYP1) act downstream of the AHR and metabolize small molecules. However, it is currently unknown whether CYP1 activity is relevant for immune modulation. We studied the interdependence of CYP1 and AHR in human primary immune cells using pharmacological methods. CYP1 inhibition increased the expression levels of the stem cell factor receptor (c-Kit) and interleukin (IL)-22 but decreased IL-17. Single cell analyses showed that CYP1 inhibition especially promoted CD4+ helper T (Th) cells that co-express c-Kit and IL-22 simultaneously. The addition of an AHR antagonist reversed all these effects. In addition to T cells, we screened other human immune cells for CYP and found cell-specific fingerprints, suggesting that similar mechanisms are present in multiple immune cells. We describe a feedback loop yet unknown in human immune cells where CYP1 inhibition resulted in an altered AHR-dependent immune response. This mechanism relates CYP1-dependent metabolism of environmental small molecules to human immunity. PMID:28276465

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

    PubMed

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

    2016-03-08

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

  12. Healthy Change Processes-A Diary Study of Five Organizational Units. Establishing a Healthy Change Feedback Loop.

    PubMed

    Lien, Mathilde; Saksvik, Per Øystein

    2016-10-01

    This paper explores a change process in the Central Norway Regional Health Authority that was brought about by the implementation of a new economics and logistics system. The purpose of this paper is to contribute to understanding of how employees' attitudes towards change develop over time and how attitudes differ between the five health trusts under this authority. In this paper, we argue that a process-oriented focus through a longitudinal diary method, in addition to action research and feedback loops, will provide greater understanding of the evaluation of organizational change and interventions. This is explored through the assumption that different units will have different perspectives and attitudes towards the same intervention over time because of different contextual and time-related factors. The diary method aims to capture the context, events, reflections and interactions when they occur and allows for a nuanced frame of reference for the different phases of the implementation process and how these phases are perceived by employees. Copyright © 2016 John Wiley & Sons, Ltd.

  13. 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.

  14. The balance mediated by miRNAs and the heme oxygenase 1 feedback loop contributes to biological effects.

    PubMed

    Ma, Ning; Xiang, Ying; Zhang, Yanfen; Zhao, Xia; Zhou, Lingyun; Gao, Xu

    2013-12-01

    Heme oxygenase-1 (HMOX1) is a ubiquitously expressed inducible enzyme that degrades heme to carbon monoxide, biliverdin, and free iron ions. Since 1950, many studies have revealed the role of HMOX1 in reducing the impact of oxidative stress in many types of diseases, such as Alzheimer's disease, heart disease, and the development of tumors. These effects arise as a result of the removal of heme, the biological activities of the products of HMOX1 and the activity of HMOX1 itself. However, HMOX1 has some contradictory effects. The discovery of microRNAs (miRNAs) and their relationship with HMOX1 has provided a new direction for research in this field. Here, we discuss the role of a potential regulatory feedback loop between HMOX1 and miRNAs in pathological processes based on recently published data. We hope to describe a new mechanism for HMOX1 function based on miRNAs to address the contradictory results reported in the literature.

  15. 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.

  16. A 3-SYNAPSE POSITIVE FEEDBACK LOOP REGULATES THE EXCITABILITY OF AN INTERNEURON CRITICAL FOR SENSITIZATION IN THE LEECH

    PubMed Central

    Crisp, Kevin M.; Muller, Kenneth J.

    2007-01-01

    Sensitization of reflexive shortening in the leech has been linked to serotonin (5-HT)-induced changes in the excitability of a single interneuron, the S cell. This neuron is necessary for sensitization and complete dishabituation of reflexive shortening, during which it contributes to the sensory-motor reflex. The S cell does not contain 5-HT, which is released primarily from the Retzius (R) cells, whose firing enhances S-cell excitability. Here we show that the S cell excites the R cells, mainly via a fast disynaptic pathway in which the first synapse is the electrical junction between the S cell and the coupling interneurons, and the second synapse is a glutamatergic synapse of the coupling interneurons onto the R cells. The S cell-triggered excitatory postsynaptic potential in the R cell diminishes and nearly disappears in elevated concentrations of divalent cations because the coupling interneurons become inexcitable under these conditions. Serotonin released from the R cells feeds back upon the S cell and increases its excitability by activating a 5-HT7-like receptor; 5-methoxytryptamine (5-MeOT; 10 μM) mimics the effects of 5-HT on S cell excitability, and effects of both 5-HT and 5-MeOT are blocked by pimozide (10 μM) and SB-269970 (5 μM). This feedback loop may be critical for the full expression of sensitization of reflexive shortening. PMID:16571760

  17. A closed-loop automatic control system for high-intensity acoustic test systems.

    NASA Technical Reports Server (NTRS)

    Slusser, R. A.

    1973-01-01

    Description of an automatic control system for high-intensity acoustic tests in reverberation chambers. Working in 14 one-third-octave bands from 50 to 1000 Hz, the desired sound pressure levels are set into the memory in the control system before the test. The control system then increases the sound pressure level in the reverberation chamber gradually in each of the one-third-octave bands until the level set in the memory is reached. This level is then maintained for the duration of the test. Additional features of the system are overtest protection, the capability of 'holding' the spectrum at any time, and the presence of a total test timer.

  18. 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.

  19. Generalized Discrete Model of Systems with Distributed Feedback Based on Surface Acoustic Waves

    NASA Astrophysics Data System (ADS)

    Sveshnikov, B. V.; Bagdasaryan, A. S.

    2016-11-01

    We have developed a self-consistent physical model that improves the accuracy of calculating the characteristics of the devices based on both surface and pseudosurface acoustic waves. The model is free from restrictions inherent in the well-known method of coupled modes and other phenomenological methods for studying distributed systems. The compact relationships describing all the characteristics of the acoustoelectric transducers of all types with allowance for the possible directionality of their radiation and its propagation loss are obtained using analytical solution of the difference equations. The method for determining the spatial orientation of the elastic-polarization ellipse in an anisotropic crystal, which allows one to unambiguously calculate the phase shift between the oscillations of two coupled dynamical subsystems, i.e., elastic displacements and the corresponding electric field, is proposed. The obtained results, which considerably facilitate the task of fast and accurate design of various devices on the basis of surface and pseudosurface acoustic waves, are valid in the general case for any frequency, including the harmonics of the frequency of the fundamental acoustic synchronism.

  20. Iterative Frequency Domain Decision Feedback Equalization and Decoding for Underwater Acoustic Communications

    NASA Astrophysics Data System (ADS)

    Zhao, Liang; Ge, Jian-Hua

    2012-12-01

    Single-carrier (SC) transmission with frequency-domain equalization (FDE) is today recognized as an attractive alternative to orthogonal frequency-division multiplexing (OFDM) for communication application with the inter-symbol interference (ISI) caused by multi-path propagation, especially in shallow water channel. In this paper, we investigate an iterative receiver based on minimum mean square error (MMSE) decision feedback equalizer (DFE) with symbol rate and fractional rate samplings in the frequency domain (FD) and serially concatenated trellis coded modulation (SCTCM) decoder. Based on sound speed profiles (SSP) measured in the lake and finite-element ray tracking (Bellhop) method, the shallow water channel is constructed to evaluate the performance of the proposed iterative receiver. Performance results show that the proposed iterative receiver can significantly improve the performance and obtain better data transmission than FD linear and adaptive decision feedback equalizers, especially in adopting fractional rate sampling.

  1. Disturbance of the let-7/LIN28 double-negative feedback loop is associated with radio- and chemo-resistance in non-small cell lung cancer

    PubMed Central

    Hu, Weimin; Yang, Guangping; Yu, Hui; Wang, Ruihao; Wang, Linjing; Zhang, Guoqian; Fu, Wenfan; Dai, Lu; Li, Wanzhen; Liao, Boyu; Zhang, Shuxu

    2017-01-01

    Radio- and chemo-resistance represent major obstacles in the therapy of non-small-cell lung cancer (NSCLC) and the underlying molecular mechanisms are not known. In the present study, during induction of radio- or chemo-resistance in NSCLC cells, dynamic analyses revealed that decreased expression of let-7 induced by irradiation or cisplatin resulted in increased expression of its target gene LIN28, and increased expression of LIN28 then contributed to further decreased expression of let-7 by inhibiting its maturation and biogenesis. Moreover, we showed that down-regulation of let-7 and up-regulation of LIN28 expression promoted resistance to irradiation or cisplatin by regulating the single-cell proliferative capability of NSCLC cells. Consequently, in NSCLC cells, let-7 and LIN28 can form a double-negative feedback loop through mutual inhibition, and disturbance of the let-7/LIN28 double-negative feedback loop induced by irradiation or chemotherapeutic drugs can result in radio- and chemo-resistance. In addition, low expression of let-7 and high expression of LIN28 in NSCLC patients was associated significantly with resistance to radiotherapy or chemotherapy. Therefore, our study demonstrated that disturbance of the let-7/LIN28 double-negative feedback loop is involved in the regulation of radio- and chemo-resistance, and that let-7 and LIN28 could be employed as predictive biomarkers of response to radiotherapy or chemotherapy in NSCLC patients. PMID:28235063

  2. FOXM1 confers resistance to gefitinib in lung adenocarcinoma via a MET/AKT-dependent positive feedback loop.

    PubMed

    Wang, Yu; Zhang, Weiwei; Wen, Li; Yang, Huiling; Wen, Mingling; Yun, Yuyu; Zhao, Lisheng; Zhu, Xiaofei; Tian, Li; Luo, Erping; Li, Yu; Liu, Wenchao; Wen, Ning

    2016-09-13

    Gefitinib resistance remains a major problem in the treatment of lung adenocarcinoma. However, the molecular mechanisms of gefitinib resistance are not fully understood. In this study, we characterized the critical role of transcription factor Forkhead box protein M1 (FOXM1) in gefitinib resistance of lung adenocarcinoma cells. In vitro drug sensitivity assays demonstrated that FOXM1 inhibition sensitized PC9/GR and HCC827/GR cells to gefitinib, whereas FOXM1 overexpression enhanced PC9 and HCC827 cell resistance to gefitinib. Increased FOXM1 resulted in the upregulation of hepatocyte growth factor receptor (MET), which led to activation of the protein kinase B (AKT) pathway, whereas knockdown of FOXM1 did the opposite. FOXM1 bound directly to the MET promoter regions and regulated the promoter activities and the expression of MET at the transcriptional level. Moreover, MET/AKT pathway upregulated the expression of FOXM1 in lung adenocarcinoma cells. Inhibition of pAKT by LY294002 or inhibition of pMET by PHA-665752 significantly inhibited the expression of FOXM1 in lung adenocarcinoma cells. Importantly, we further demonstrated that the expression levels of FOXM1, pAKT and MET were significantly increased in lung adenocarcinoma tissues relative to normal lung tissues, and these three biomarkers were concomitantly overexpressed in lung adenocarcinoma tissues. Taken together, our results indicate that FOXM1 promotes acquired resistance to gefitinib of lung adenocarcinoma cells, and FOXM1 crosstalks with MET/AKT signaling to form a positive feedback loop to promote lung adenocarcinoma development.

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

    PubMed Central

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

    2016-01-01

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

  4. The feedback loop of LITAF and BCL6 is involved in regulating apoptosis in B cell non-Hodgkin's-lymphoma

    PubMed Central

    Shi, Yaoyao; Kuai, Yue; Lei, Lizhen; Weng, Yuanyuan; Berberich-Siebelt, Friederike; Zhang, Xinxia; Wang, Jinjie; Zhou, Yuan; Jiang, Xin; Ren, Guoping; Pan, Hongyang; Mao, Zhengrong; Zhou, Ren

    2016-01-01

    Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6. Therefore, we sought to explore the feedback loop between LITAF and BCL6 in B-NHL. Here, our data for the first time show that LITAF can repress expression of BCL6 by binding to Region A (−87 to +65) containing a putative LITAF-binding motif (CTCCC) within the BCL6 promoter. Furthermore, the regulation of BCL6 targets (PRDM1 or c-Myc) by LITAF may be associated with B-cell differentiation. Results also demonstrate that ectopic expression of LITAF induces cell apoptosis, activated by releasing cytochrome c, cleaving PARP and caspase 3 in B-NHL cells whereas knockdown of LITAF robustly protected cells from apoptosis. Interestingly, BCL6, in turn, could reverse cell apoptosis mediated by LITAF. Collectively, our findings provide a novel apoptotic regulatory pathway in which LITAF, as a transcription factor, inhibits the expression of BCL6, which leads to activation of the intrinsic mitochondrial pathway and tumor apoptosis. Our study is expected to provide a possible biomarker as well as a target for clinical therapies to promote tumor cell apoptosis. PMID:27764808

  5. FOXM1 confers resistance to gefitinib in lung adenocarcinoma via a MET/AKT-dependent positive feedback loop

    PubMed Central

    Wen, Mingling; Yun, Yuyu; Zhao, Lisheng; Zhu, Xiaofei; Tian, Li; Luo, Erping; Li, Yu; Liu, Wenchao; Wen, Ning

    2016-01-01

    Gefitinib resistance remains a major problem in the treatment of lung adenocarcinoma. However, the molecular mechanisms of gefitinib resistance are not fully understood. In this study, we characterized the critical role of transcription factor Forkhead box protein M1 (FOXM1) in gefitinib resistance of lung adenocarcinoma cells. In vitro drug sensitivity assays demonstrated that FOXM1 inhibition sensitized PC9/GR and HCC827/GR cells to gefitinib, whereas FOXM1 overexpression enhanced PC9 and HCC827 cell resistance to gefitinib. Increased FOXM1 resulted in the upregulation of hepatocyte growth factor receptor (MET), which led to activation of the protein kinase B (AKT) pathway, whereas knockdown of FOXM1 did the opposite. FOXM1 bound directly to the MET promoter regions and regulated the promoter activities and the expression of MET at the transcriptional level. Moreover, MET/AKT pathway upregulated the expression of FOXM1 in lung adenocarcinoma cells. Inhibition of pAKT by LY294002 or inhibition of pMET by PHA-665752 significantly inhibited the expression of FOXM1 in lung adenocarcinoma cells. Importantly, we further demonstrated that the expression levels of FOXM1, pAKT and MET were significantly increased in lung adenocarcinoma tissues relative to normal lung tissues, and these three biomarkers were concomitantly overexpressed in lung adenocarcinoma tissues. Taken together, our results indicate that FOXM1 promotes acquired resistance to gefitinib of lung adenocarcinoma cells, and FOXM1 crosstalks with MET/AKT signaling to form a positive feedback loop to promote lung adenocarcinoma development. PMID:27494877

  6. 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

  7. 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

  8. Feedback looping between ChREBP and PPARα in the regulation of lipid metabolism in brown adipose tissues.

    PubMed

    Iizuka, Katsumi; Wu, Wudelehu; Horikawa, Yukio; Saito, Masayuki; Takeda, Jun

    2013-01-01

    Carbohydrate response element binding protein (ChREBP) and peroxisome proliferator-activated receptor alpha (PPARα) play an important role in the regulation of lipid metabolism in the liver. Chrebp and Ppara mRNA levels are equally abundant in brown adipose tissue and liver. However, their functions in brown adipose tissues are unclear. In this study, we attempted to clarify the role of ChREBP and PPARα using brown adipose HB2 cell lines and tissues from wild type and Chrebp-/- C57BL/6J mice. In liver and brown adipose tissues, Chrebpb mRNA levels in the fasting state were much lower than those fed ad libitum, while Ppara mRNA levels in the fasting state were much higher than in the fed state. In differentiated brown adipose HB2 cell lines, glucose increased mRNA levels of ChREBP target genes such as Chrebpb, Fasn, and Glut4 in a dose dependent manner, while glucose decreased both Chrebpa and Ppara mRNA levels. Accordingly, adenoviral overexpression of ChREBP and a reporter assay demonstrated that ChREBP partially suppressed Ppara and Acox mRNA expression. Moreover, in brown adipose tissues from Chrebp-/- mice, Chrebpb and Fasn mRNA levels in the ad libitum fed state were much lower than those in the fasting state, while Ppara and Acox mRNA levels were not. Finally, using Wy14,643, a selective PPARα agonist, and overexpression of PPARα partially suppressed glucose induction of Chrebpb and Fasn mRNA in HB2 cells. In conclusion, the feedback loop between ChREBP and PPARα plays an important role in the regulation of lipogenesis in brown adipocytes.

  9. Acoustics

    NASA Technical Reports Server (NTRS)

    Goodman, Jerry R.; Grosveld, Ferdinand

    2007-01-01

    The acoustics environment in space operations is important to maintain at manageable levels so that the crewperson can remain safe, functional, effective, and reasonably comfortable. High acoustic levels can produce temporary or permanent hearing loss, or cause other physiological symptoms such as auditory pain, headaches, discomfort, strain in the vocal cords, or fatigue. Noise is defined as undesirable sound. Excessive noise may result in psychological effects such as irritability, inability to concentrate, decrease in productivity, annoyance, errors in judgment, and distraction. A noisy environment can also result in the inability to sleep, or sleep well. Elevated noise levels can affect the ability to communicate, understand what is being said, hear what is going on in the environment, degrade crew performance and operations, and create habitability concerns. Superfluous noise emissions can also create the inability to hear alarms or other important auditory cues such as an equipment malfunctioning. Recent space flight experience, evaluations of the requirements in crew habitable areas, and lessons learned (Goodman 2003; Allen and Goodman 2003; Pilkinton 2003; Grosveld et al. 2003) show the importance of maintaining an acceptable acoustics environment. This is best accomplished by having a high-quality set of limits/requirements early in the program, the "designing in" of acoustics in the development of hardware and systems, and by monitoring, testing and verifying the levels to ensure that they are acceptable.

  10. Reinforcing feedback loop of renal cyclic guanosine 3' 5' -monophosphate and interstitial hydrostatic pressure in pressure-natriuresis.

    PubMed

    Lieb, David C; Kemp, Brandon A; Howell, Nancy L; Gildea, John J; Carey, Robert M

    2009-12-01

    This study addresses the hypothesis that renal interstitial (RI) cGMP, a modulator of pressure-natriuresis, exerts its effect through a relationship with renal interstitial hydrostatic pressure (RIHP). Increasing renal perfusion pressure in Sprague-Dawley rats led to increases in RIHP (5.2+/-0.6 to 10.9+/-1.6 mm Hg; P<0.01), urine sodium excretion (0.062+/-0.009 to 0.420+/-0.068 micromol/min per gram; P<0.01), and RI cGMP (3.5+/-0.8 to 9.5+/-1.7 fmol/min; P<0.01), and these effects were blocked by partial renal decapsulation. Infusion of cGMP into the RI compartment of decapsulated animals restored natriuresis (0.067+/-0.010 to 0.310+/-0.061 micromol/min per gram; P<0.01). These changes were independent of changes in glomerular filtration rate . Artificially increasing RIHP in normotensive animals increased RI cGMP (4.1+/-0.6 to 6.9+/-0.7 fmol/min; P<0.01) and urine sodium excretion (0.071+/-0.013 to 0.179+/-0.039 micromol/min per gram; P<0.05). Coinfusion of organic anion transport-inhibitor probenecid, or soluble guanylyl cyclase inhibitor 1-H(1,2,4) oxadiazolo-(4,2)quinoxalin-1-one, abolished these effects. Infusion of cGMP into the RI compartment of normotensive animals increased RIHP (6.7+/-0.4 to 10.3+/-0.9 mm Hg; P<0.001). Exogenous RI cGMP delivery did not affect total, cortical, or medullary renal blood flow. These studies suggest that extracellular RI cGMP is required for the natriuresis observed after increases in renal perfusion pressure and RIHP and that cGMP acts via a tubule mechanism. The results support an intrarenal positive-feedback loop wherein RI cGMP increases RIHP, which, in turn, increases RI cGMP, contributing to the reinforcement of pressure-natriuresis.

  11. Acoustic emission sensor system using a chirped fiber-Bragg-grating Fabry-Perot interferometer and smart feedback control.

    PubMed

    Zhang, Qi; Zhu, Yupeng; Luo, Xiangyu; Liu, Guigen; Han, Ming

    2017-02-01

    We demonstrate a fiber-optic acoustic emission (AE) sensor system that is capable of performing AE detection, even when the sensor is experiencing large quasi-static strains. The sensor is a Fabry-Perot interferometer formed by cascaded chirped fiber-Bragg gratings (CFBGs). The reflection spectrum of the sensor features a number of narrow spectral notches equally spaced within the reflection bandwidth of the CFBG. A semiconductor laser whose wavelength can be fast tuned through current injection is used to lock the laser line to the center of a slope of a spectral notch. When the notch is knocked out of the tuning range of the laser, a neighboring notch moves into the range. Through a smart feedback control scheme, the laser is unlocked from the current spectral lock and relocked to the desired point of the new notch. The fast speed of the unlocking/relocking process (<1  ms) ensures that the AE signal is monitored without significant disruption.

  12. CCL2/EGF positive feedback loop between cancer cells and macrophages promotes cell migration and invasion in head and neck squamous cell carcinoma

    PubMed Central

    Li, Hui-min; Yang, Jie-gang; Ren, Jian-Gang; He, Ke-fei; Liu, Bing; Zhang, Wei; Zhao, Yi-Fang

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) represents the most frequent malignancy in the head and neck region, and the survival rate has not been improved significantly over the past three decades. It has been reported the infiltrated macrophages contribute to the malignant progression of HNSCC. However, the crosstalk between macrophages and cancer cells remains poorly understood. In the present study, we explored interactions between monocytes/macrophages and HNSCC cells by establishing the direct co-culture system, and found that the crosstalk promoted the migration and invasion of cancer cells by enhancing the invadopodia formation through a CCL2/EGF positive feedback loop. Our results demonstrated HNSCC cells educated monocytes into M2-like macrophages by releasing C-C motif chemokine ligand 2 (CCL2, or MCP-1). And the M2-like macrophages secreted epithelial growth factor (EGF), which increased the motility of HNSCC cells by enhancing the invadopodia formation. These subcellular pseudopodia degraded extracellular matrix (ECM), facilitating tumor local invasion and distant metastasis. Moreover, EGF up-regulated CCL2 expression in HNSCC cells, which recruited monocytes and turned them into M2-like macrophages, thus forming a positive feedback paracrine loop. Finally, we reported that curcumin, a powerful natural drug, suppressed the production of EGF and CCL2 in macrophages and cancer cells, respectively, blocking the feedback loop and suppressing the migration and invasion of HNSCC cells. These results shed light on the possibilities and approaches based on targeting the crosstalk between cancer cells and monocytes/macrophages in HNSCC for potential cancer therapy. PMID:27888616

  13. HER2 phosphorylation is maintained by a PKB negative feedback loop in response to anti-HER2 herceptin in breast cancer.

    PubMed

    Gijsen, Merel; King, Peter; Perera, Tim; Parker, Peter J; Harris, Adrian L; Larijani, Banafshé; Kong, Anthony

    2010-12-21

    Herceptin (trastuzumab) is used in patients with breast cancer who have HER2 (ErbB2)-positive tumours. However, its mechanisms of action and how acquired resistance to Herceptin occurs are still poorly understood. It was previously thought that the anti-HER2 monoclonal antibody Herceptin inhibits HER2 signalling, but recent studies have shown that Herceptin does not decrease HER2 phosphorylation. Its failure to abolish HER2 phosphorylation may be a key to why acquired resistance inevitably occurs for all responders if Herceptin is given as monotherapy. To date, no studies have explained why Herceptin does not abolish HER2 phosphorylation. The objective of this study was to investigate why Herceptin did not decrease HER2 phosphorylation despite being an anti-HER2 monoclonal antibody. We also investigated the effects of acute and chronic Herceptin treatment on HER3 and PKB phosphorylation in HER2-positive breast cancer cells. Using both Förster resonance energy transfer (FRET) methodology and conventional Western blot, we have found the molecular mechanisms whereby Herceptin fails to abolish HER2 phosphorylation. HER2 phosphorylation is maintained by ligand-mediated activation of EGFR, HER3, and HER4 receptors, resulting in their dimerisation with HER2. The release of HER ligands was mediated by ADAM17 through a PKB negative feedback loop. The feedback loop was activated because of the inhibition of PKB by Herceptin treatment since up-regulation of HER ligands and ADAM17 also occurred when PKB phosphorylation was inhibited by a PKB inhibitor (Akt inhibitor VIII, Akti-1/2). The combination of Herceptin with ADAM17 inhibitors or the panHER inhibitor JNJ-26483327 was able to abrogate the feedback loop and decrease HER2 phosphorylation. Furthermore, the combination of Herceptin with JNJ-26483327 was synergistic in tumour inhibition in a BT474 xenograft model. We have determined that a PKB negative feedback loop links ADAM17 and HER ligands in maintaining HER2

  14. 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

  15. 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

  16. 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.

  17. IL-6R/STAT3/miR-204 feedback loop contributes to cisplatin resistance of epithelial ovarian cancer cells.

    PubMed

    Zhu, Xiaolan; Shen, Huiling; Yin, Xinming; Long, Lulu; Chen, Xiaofang; Feng, Fan; Liu, Yueqin; Zhao, Peiqing; Xu, Yue; Li, Mei; Xu, Wenlin; Li, Yuefeng

    2017-03-27

    Enhanced chemoresistance is, among other factors, believed to be responsible for treatment failure and tumor relapse in patients with epithelial ovarian cancer (EOC). Here, we exposed EOC cells to interleukin-6 (IL-6) to activate oncogenic STAT3, which directly repressed miR-204 via a conserved STAT3-binding site near the TRPM3 promoter region upstream of miR-204. Repression of miR-204 was required for IL-6-induced cisplatin (cDDP) resistance. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6-dependent STAT3 activation, as a direct miR-204 target. Importantly, the resulting IL-6R/STAT3/miR-204 feedback loop was identified in patients with EOC, and its activity correlated with chemosensitivity. Moreover, exogenous miR-204 blocked this circuit and enhanced cDDP sensitivity both in vitro and in vivo by inactivating IL-6R/STAT3 signaling and subsequently decreasing the expression of anti-apoptotic proteins. Our findings illustrate the function of this feedback loop in cDDP-based therapy and may offer a broadly useful approach to improve EOC therapy.

  18. A positive feedback loop between ROS and Mxi1-0 promotes hypoxia-induced VEGF expression in human hepatocellular carcinoma cells.

    PubMed

    Hu, Zhenzhen; Dong, Na; Lu, Dian; Jiang, Xiuqin; Xu, Jinjin; Wu, Zhiwei; Zheng, Datong; Wechsler, Daniel S

    2017-02-01

    VEGF expression induced by hypoxia plays a critical role in promoting tumor angiogenesis. However, the molecular mechanism that modulates VEGF expression under hypoxia is still poorly understood. In this study, we found that VEGF induction in hypoxic HepG2 cells is ROS-dependent. ROS mediates hypoxia-induced VEGF by upregulation of Mxi1-0. Furthermore, PI3K/AKT/HIF-1α signaling pathway is involved in ROS-mediated Mxi1-0 and VEGF expression in hypoxic HepG2 cells. Finally, Mxi1-0 could in turn regulate ROS generation in hypoxic HepG2 cells, creating a positive feedback loop. Taken together, this study demonstrate a positive regulatory feedback loop in which ROS mediates hypoxia-induced Mxi1-0 via activation of PI3K/AKT/HIF-1α pathway, events that in turn elevate ROS generation and promote hypoxia-induced VEGF expression. These findings could provide a rationale for designing new therapies based on inhibition of hepatocellular carcinoma (HCC) angiogenesis.

  19. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer

    PubMed Central

    Carracedo, Arkaitz; Ma, Li; Teruya-Feldstein, Julie; Rojo, Federico; Salmena, Leonardo; Alimonti, Andrea; Egia, Ainara; Sasaki, Atsuo T.; Thomas, George; Kozma, Sara C.; Papa, Antonella; Nardella, Caterina; Cantley, Lewis C.; Baselga, Jose; Pandolfi, Pier Paolo

    2008-01-01

    Numerous studies have established a causal link between aberrant mammalian target of rapamycin (mTOR) activation and tumorigenesis, indicating that mTOR inhibition may have therapeutic potential. In this study, we show that rapamycin and its analogs activate the MAPK pathway in human cancer, in what represents a novel mTORC1-MAPK feedback loop. We found that tumor samples from patients with biopsy-accessible solid tumors of advanced disease treated with RAD001, a rapamycin derivative, showed an administration schedule–dependent increase in activation of the MAPK pathway. RAD001 treatment also led to MAPK activation in a mouse model of prostate cancer. We further show that rapamycin-induced MAPK activation occurs in both normal cells and cancer cells lines and that this feedback loop depends on an S6K-PI3K-Ras pathway. Significantly, pharmacological inhibition of the MAPK pathway enhanced the antitumoral effect of mTORC1 inhibition by rapamycin in cancer cells in vitro and in a xenograft mouse model. Taken together, our findings identify MAPK activation as a consequence of mTORC1 inhibition and underscore the potential of a combined therapeutic approach with mTORC1 and MAPK inhibitors, currently employed as single agents in the clinic, for the treatment of human cancers. PMID:18725988

  20. The oncogenic transcription factor IRF4 is regulated by a novel CD30/NF-κB positive feedback loop in peripheral T-cell lymphoma

    PubMed Central

    Boddicker, Rebecca L.; Kip, N. Sertac; Xing, Xiaoming; Zeng, Yu; Yang, Zhi-Zhang; Lee, Jeong-Heon; Almada, Luciana L.; Elsawa, Sherine F.; Knudson, Ryan A.; Law, Mark E.; Ketterling, Rhett P.; Cunningham, Julie M.; Wu, Yanhong; Maurer, Matthew J.; O’Byrne, Megan M.; Cerhan, James R.; Slager, Susan L.; Link, Brian K.; Porcher, Julie C.; Grote, Deanna M.; Jelinek, Diane F.; Dogan, Ahmet; Ansell, Stephen M.; Fernandez-Zapico, Martin E.

    2015-01-01

    Peripheral T-cell lymphomas (PTCLs) are generally aggressive non-Hodgkin lymphomas with poor overall survival rates following standard therapy. One-third of PTCLs express interferon regulatory factor-4 (IRF4), a tightly regulated transcription factor involved in lymphocyte growth and differentiation. IRF4 drives tumor growth in several lymphoid malignancies and has been proposed as a candidate therapeutic target. Because direct IRF4 inhibitors are not clinically available, we sought to characterize the mechanism by which IRF4 expression is regulated in PTCLs. We demonstrated that IRF4 is constitutively expressed in PTCL cells and drives Myc expression and proliferation. Using an inhibitor screen, we identified nuclear factor κB (NF-κB) as a candidate regulator of IRF4 expression and cell proliferation. We then demonstrated that the NF-κB subunits p52 and RelB were transcriptional activators of IRF4. Further analysis showed that activation of CD30 promotes p52 and RelB activity and subsequent IRF4 expression. Finally, we showed that IRF4 transcriptionally regulates CD30 expression. Taken together, these data demonstrate a novel positive feedback loop involving CD30, NF-κB, and IRF4; further evidence for this mechanism was demonstrated in human PTCL tissue samples. Accordingly, NF-κB inhibitors may represent a clinical means to disrupt this feedback loop in IRF4-positive PTCLs. PMID:25833963

  1. 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.

  2. 4E-BP2/SH2B1/IRS2 Are Part of a Novel Feedback Loop That Controls β-Cell Mass.

    PubMed

    Blandino-Rosano, Manuel; Scheys, Joshua O; Jimenez-Palomares, Margarita; Barbaresso, Rebecca; Bender, Aaron S; Yanagiya, Akiko; Liu, Ming; Rui, Liangyou; Sonenberg, Nahum; Bernal-Mizrachi, Ernesto

    2016-08-01

    The mammalian target of rapamycin complex 1 (mTORC1) regulates several biological processes, although the key downstream mechanisms responsible for these effects are poorly defined. Using mice with deletion of eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2), we determine that this downstream target is a major regulator of glucose homeostasis and β-cell mass, proliferation, and survival by increasing insulin receptor substrate 2 (IRS2) levels and identify a novel feedback mechanism by which mTORC1 signaling increases IRS2 levels. In this feedback loop, we show that 4E-BP2 deletion induces translation of the adaptor protein SH2B1 and promotes the formation of a complex with IRS2 and Janus kinase 2, preventing IRS2 ubiquitination. The changes in IRS2 levels result in increases in cell cycle progression, cell survival, and β-cell mass by increasing Akt signaling and reducing p27 levels. Importantly, 4E-BP2 deletion confers resistance to cytokine treatment in vitro. Our data identify SH2B1 as a major regulator of IRS2 stability, demonstrate a novel feedback mechanism linking mTORC1 signaling with IRS2, and identify 4E-BP2 as a major regulator of proliferation and survival of β-cells.

  3. 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

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

    NASA Technical Reports Server (NTRS)

    Birchenough, A. G.

    1975-01-01

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

  5. 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.

  6. Applied topology optimization of vibro-acoustic hearing instrument models

    NASA Astrophysics Data System (ADS)

    Søndergaard, Morten Birkmose; Pedersen, Claus B. W.

    2014-02-01

    Designing hearing instruments remains an acoustic challenge as users request small designs for comfortable wear and cosmetic appeal and at the same time require sufficient amplification from the device. First, to ensure proper amplification in the device, a critical design challenge in the hearing instrument is to minimize the feedback between the outputs (generated sound and vibrations) from the receiver looping back into the microphones. Secondly, the feedback signal is minimized using time consuming trial-and-error design procedures for physical prototypes and virtual models using finite element analysis. In the present work it is demonstrated that structural topology optimization of vibro-acoustic finite element models can be used to both sufficiently minimize the feedback signal and to reduce the time consuming trial-and-error design approach. The structural topology optimization of a vibro-acoustic finite element model is shown for an industrial full scale model hearing instrument.

  7. Analysis, Design, and Optimization of Matched-Impedance Wide-Band Amplifiers With Multiple Feedback Loops Using 0.18 μm Complementary Metal Oxide Semiconductor Technology

    NASA Astrophysics Data System (ADS)

    Lin, Yo-Sheng; Lee, Tai-Hsing

    2004-10-01

    The realization of matched-impedance wide-band amplifier fabricated by 0.18 μm complementary metal oxide semiconductor (CMOS) process is reported. The technique of multiple feedback loops was used in the amplifier for terminal impedance matching and wide bandwidth simultaneously. The experimental results show that 3-dB bandwidth of 3 GHz and a gain of 10.7 dB with in-band input/output return loss more than 10 dB are obtained. These values agree well with those predicted from the analytic expressions derived for voltage gain, trans-impedance gain, bandwidth, and input/output return loss and impedance. In addition, the use of source capacitive peaking technique can improve the intrinsic over-damped characteristic of this amplifier.

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

    PubMed

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

    2013-11-01

    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.

  9. 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.

  10. 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.

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

    PubMed

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

    2015-05-10

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

  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. 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.

  14. HIC1 and miR-23~27~24 clusters form a double-negative feedback loop in breast cancer

    PubMed Central

    Wang, Yanbo; Liang, Hongwei; Zhou, Geyu; Hu, Xiuting; Liu, Zhengya; Jin, Fangfang; Yu, Mengchao; Sang, Jianfeng; Zhou, Yong; Fu, Zheng; Zhang, Chen-Yu; Zhang, Weijie; Zen, Ke; Chen, Xi

    2017-01-01

    MicroRNAs (miRNAs) have emerged as a major regulator of the initiation and progression of human cancers, including breast cancer. However, the cooperative effects and transcriptional regulation of multiple miRNAs, especially miRNAs that are present in clusters, remain largely undiscovered. Here we showed that all members of the miR-23~27~24 clusters are upregulated and function as oncogenes in breast cancer and simultaneously target HIC1. Furthermore, we found that HIC1 functions as a transcriptional repressor to negatively control the expression of miR-23~27~24 clusters and forms a double-negative (overall positive) feedback loop. This feedback regulatory pathway is important because overexpression of miR-23~27~24 clusters can remarkably accelerate tumor growth, whereas restoration of HIC1 significantly blocks tumor growth in vivo. A mathematical model was created to quantitatively illustrate the regulatory circuit. Our finding highlights the cooperative effects of miRNAs in a cluster and adds another layer of complexity to the miRNA regulatory network. This study may also provide insight into the molecular mechanisms of breast cancer progression. PMID:28009350

  15. PATZ1 induces PP4R2 to form a negative feedback loop on IKK/NF-κB signaling in lung cancer

    PubMed Central

    Ho, Ming-Yi; Liang, Chi-Ming; Liang, Shu-Mei

    2016-01-01

    Activation of IKK enhances NF-κB signaling to facilitate cancer cell migration, invasion and metastasis. Here, we uncover the existence of a negative feedback loop of IKK. The transcription factor PATZ1 induces protein phosphatase-4 (PP4) regulatory subunit 2 (PP4R2) in an IKK-dependent manner. PP4R2 enhances the binding of PP4 to phosphorylated IKK to inactivate IKK/NF-κB signaling during sustained stimulation by cellular stimuli such as growth factors and inflammatory mediators. Matched pair studies reveal that primary lung cancers express more PATZ1 and PP4R2 than lymph node metastases in patients. Ectopic PATZ1 decreases invasion/colonization of lung cancers and prolongs the survival of xenograft mice. These effects of PATZ1 are reversed by downregulating PP4R2. Our results suggest that PATZ1 and PP4R2 provide negative feedback on IKK/NF-κB signaling to prevent cancer cells from over-stimulation from cellular stimuli; a decline in PATZ1 and PP4R2 is functionally associated with cancer migration/invasion and agents enhancing PATZ1 and PP4R2 are worth exploring to prevent invasion/metastasis of lung cancers. PMID:27391343

  16. 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.

  17. The Arabidopsis NAC transcription factor NTL4 participates in a positive feedback loop that induces programmed cell death under heat stress conditions.

    PubMed

    Lee, Sangmin; Lee, Hyo-Jun; Huh, Sung Un; Paek, Kyung-Hee; Ha, Jun-Ho; Park, Chung-Mo

    2014-10-01

    Programmed cell death (PCD) is an integral component of plant development and adaptation under adverse environmental conditions. Reactive oxygen species (ROS) are one of the most important players that trigger PCD in plants, and ROS-generating machinery is activated in plant cells undergoing PCD. The membrane-bound NAC transcription factor NTL4 has recently been proven to facilitate ROS production in response to drought stress in Arabidopsis. In this work, we show that NTL4 participates in a positive feedback loop that bursts ROS accumulation to modulate PCD under heat stress conditions. Heat stress induces NTL4 gene transcription and NTL4 protein processing. The level of hydrogen peroxide (H2O2) was elevated in 35S:4ΔC transgenic plants that overexpress a transcriptionally active nuclear NTL4 form but significantly reduced in NTL4-deficient ntl4 mutants under heat stress conditions. In addition, heat stress-induced cell death was accelerated in the 35S:4ΔC transgenic plants but decreased in the ntl4 mutants. Notably, H2O2 triggers NTL4 gene transcription and NTL4 protein processing under heat stress conditions. On the basis of these findings, we conclude that NTL4 modulates PCD through a ROS-mediated positive feedback control under heat stress conditions, possibly providing an adaptation strategy by which plants ensure their survival under extreme heat stress conditions.

  18. Gain drift compensation with no feedback-loop developed for the X-Ray Integral Field Unit/ATHENA readout chain

    NASA Astrophysics Data System (ADS)

    Prêle, Damien; Voisin, Fabrice; Beillimaz, Cyril; Chen, Si; Goldwurm, Andrea

    2016-10-01

    The focal plane of the X-Ray Integral Field Unit (X-IFU) instrument of the Advanced Telescope for High-Energy Astrophysics observatory is composed of 3840 microcalorimeters. These sensors, based on superconducting transition edge sensors (TES), are read out through a frequency multiplexer. A "base-band feedback" suppresses all the carriers of the multiplexed signal in the superconducting quantum interference devices input coil (cryogenic readout). However, the loop gain of this feedback is too small (less than 10 in the present baseline of the phase A mission) to strongly compensate the readout gain drifts. An onboard x-ray source is considered to calibrate the gain of the full instrument. However, in-flight calibration time must be minimized, which leads to a requirement on the gain stability larger than 10-4 over a long duration (between each calibration) to reach the challenging energy resolution goal of 2.5 eV at 6 keV of the X-IFU. A significant part of this gain is provided by a low-noise amplifier in the warm front-end electronics (WFEE). To reach such gain stability over more than a dozen minutes, this noncooled amplifier has to cope with the temperature and supply voltage variations. Moreover, mainly for noise reasons, a common large loop gain with feedback cannot be used. We propose a new amplifier topology using diodes as loads of a differential amplifier to provide a fixed voltage gain, independent of the temperature and of the bias fluctuations. This amplifier is designed using 350-nm SiGe BiCMOS technology and is part of an integrated circuit developed for the WFEE. Our simulations provide the expected gain and noise performances. Comparison with standard resistive loaded differential pair clearly shows the advantages of the proposed amplifier topology with a gain drift decreased by more than an order of magnitude. Performances of this diode loaded amplifier are discussed in the context of the X-IFU requirements.

  19. Reflection of Propagating Slow Magneto-acoustic Waves in Hot Coronal Loops: Multi-instrument Observations and Numerical Modeling

    NASA Astrophysics Data System (ADS)

    Mandal, Sudip; Yuan, Ding; Fang, Xia; Banerjee, Dipankar; Pant, Vaibhav; Van Doorsselaere, Tom

    2016-09-01

    Slow MHD waves are important tools for understanding coronal structures and dynamics. In this paper, we report a number of observations from the X-Ray Telescope (XRT) on board HINODE and Solar Dynamic Observatory/Atmospheric Imaging Assembly (AIA) of reflecting longitudinal waves in hot coronal loops. To our knowledge, this is the first report of this kind as seen from the XRT and simultaneously with the AIA. The wave appears after a micro-flare occurs at one of the footpoints. We estimate the density and temperature of the loop plasma by performing differential emission measure (DEM) analysis on the AIA image sequence. The estimated speed of propagation is comparable to or lower than the local sound speed, suggesting it to be a propagating slow wave. The intensity perturbation amplitude, in every case, falls very rapidly as the perturbation moves along the loop and eventually vanishes after one or more reflections. To check the consistency of such reflection signatures with the obtained loop parameters, we perform a 2.5D MHD simulation, which uses the parameters obtained from our observation as inputs, and perform forward modeling to synthesize AIA 94 Å images. Analyzing the synthesized images, we obtain the same properties of the observables as for the real observation. From the analysis we conclude that a footpoint heating can generate a slow wave which then reflects back and forth in the coronal loop before fading. Our analysis of the simulated data shows that the main agent for this damping is anisotropic thermal conduction.

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  2. A feedback regulatory loop between HIF-1α and miR-21 in response to hypoxia in cardiomyocytes.

    PubMed

    Liu, Yang; Nie, Honggang; Zhang, Kuikui; Ma, Dan; Yang, Guang; Zheng, Zhilei; Liu, Kai; Yu, Bo; Zhai, Changlin; Yang, Shuang

    2014-08-25

    Accumulating evidence suggests that hypoxia-inducible factor 1α (HIF-1α) regulates numerous miRNAs and is crucial for cellular response to hypoxia. However, the relationship between HIF-1α and miR-21 in hypoxic cardiomyocytes is little known. We found that hypoxia induced HIF-1α and miR-21 expression. HIF-1α knockdown increased cell apoptosis and reduced miR-21 expression. Furthermore, we found that HIF-1α transcriptionally enhanced miR-21 promoter activity by binding to its promoter, which required the recruitment of CBP/p300. In addition, we found that miR-21 inhibition increased cell apoptosis and reduced HIF-1α expression, and modulated the PTEN/Akt pathway. Our results indicate that HIF-1α-miR-21 feedback contributes to the adaptation of cardiomyocytes to hypoxia, and has potential as therapeutic target for myocardial ischemia.

  3. Coordination of Double Strand Break Repair and Meiotic Progression in Yeast by a Mek1- Ndt80 Negative Feedback Loop.

    PubMed

    Prugar, Evelyn; Burnett, Cameron; Chen, Xiangyu; Hollingsworth, Nancy M

    2017-03-01

    During meiosis, homologous chromosomes are physically connected by crossovers and sister chromatid cohesion. Interhomolog crossovers are generated by the highly regulated repair of programmed double strand breaks (DSBs). The meiosis-specific kinase, Mek1, is critical for this regulation. Mek1 down-regulates the mitotic recombinase Rad51, indirectly promoting interhomolog strand invasion by the meiosis-specific recombinase, Dmc1. Mek1 also promotes the formation of crossovers that are distributed throughout the genome by interference and is the effector kinase for a meiosis-specific checkpoint that delays entry into Meiosis I until DSBs have been repaired. The target of this checkpoint is a meiosis-specific transcription factor, Ndt80, which is necessary to express the polo-like kinase, CDC5, and the cyclin, CLB1, thereby allowing completion of recombination and meiotic progression. This work shows that Mek1 and Ndt80 negatively feedback on each other such that when DSB levels are high, Ndt80 is inactive due to high levels of Mek1 activity. As DSBs are repaired, chromosomes synapse and Mek1 activity is reduced below a threshold that allows activation of Ndt80. Ndt80 transcription of CDC5 results in degradation of Red1, a meiosis-specific protein required for Mek1 activation, thereby abolishing Mek1 activity completely. Elimination of Mek1 kinase activity allows Rad51-mediated repair of any remaining DSBs. In this way, cells do not enter Meiosis I until recombination is complete and all DSBs are repaired.

  4. The miR-101/RUNX1 feedback regulatory loop modulates chemo-sensitivity and invasion in human lung cancer

    PubMed Central

    Wang, Xianghui; Zhao, Yihua; Qian, Haiyun; Huang, Jiangping; Cui, Fenghe; Mao, Zhifu

    2015-01-01

    The deregulation of miR-101 has been implicated in multiple cancer types including lung cancer, but the exact role, mechanisms and how silencing of miR-101 remain elusive. Here we confirmed miR-101 downregulation in lung cancer cell lines and patient tissues. Restored miR-101 expression remarkably sensitized lung cancer cells to chemotherapy and inhibited invasion. Mechanistically, we indicated that miR-101 inversely correlated with RUNX1 expression, and identified RUNX1 as a novel target of miR-101. RUNX1 impaired the effects of miR-101 on chemotherapeutic sensitization and invasion inhibition. Moreover, RUNX1 knockdown resulted into increase of miR-101 expression and elevation of luciferase activity driven by miR-101 promoter in lung cancer cells, suggesting RUNX1 negatively transcriptionally regulated miR-101 expression via physically binding to miR-101 promoter. These findings support that miR-101 downregulation accelerates the progression of lung cancer via RUNX1 dependent manner and suggest that miR-101/RUNX1 feedback axis may have therapeutic value in treating refractory lung cancer. PMID:26628987

  5. Pleckstrin homology domain-containing protein PHLDB3 supports cancer growth via a negative feedback loop involving p53

    PubMed Central

    Chao, Tengfei; Zhou, Xiang; Cao, Bo; Liao, Peng; Liu, Hongbing; Chen, Yun; Park, Hee-Won; Zeng, Shelya X.; Lu, Hua

    2016-01-01

    The tumour suppressor p53 transactivates the expression of its target genes to exert its functions. Here, we identify a pleckstrin homology domain-containing protein (PHLDB3)-encoding gene as a p53 target. PHLDB3 overexpression increases proliferation and restrains apoptosis of wild-type p53-harboring cancer cells by reducing p53 protein levels. PHLDB3 binds to MDM2 (mouse double minute 2 homolog) and facilitates MDM2-mediated ubiquitination and degradation of p53. Knockdown of PHLDB3 more efficiently inhibits the growth of mouse xenograft tumours derived from human colon cancer HCT116 cells that contain wild type p53 compared with p53-deficient HCT116 cells, and also sensitizes tumour cells to doxorubicin and 5-Fluorouracil. Analysis of cancer genomic databases reveals that PHLDB3 is amplified and/or highly expressed in numerous human cancers. Altogether, these results demonstrate that PHLDB3 promotes tumour growth by inactivating p53 in a negative feedback fashion and suggest PHLDB3 as a potential therapeutic target in various human cancers. PMID:28008906

  6. 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

  7. HGF/Met and FOXM1 form a positive feedback loop and render pancreatic cancer cells resistance to Met inhibition and aggressive phenotypes.

    PubMed

    Cui, J; Xia, T; Xie, D; Gao, Y; Jia, Z; Wei, D; Wang, L; Huang, S; Quan, M; Xie, K

    2016-09-08

    Hepatocyte growth factor (HGF)/Met signaling has critical roles in pancreatic ductal adenocarcinoma (PDA) development and progression and is considered a potential therapeutic target for this disease. However, the mechanism of aberrant activation of HGF/Met signaling and resistance to Met inhibition in PDA remains unclear. The mechanistic role of cross talk between Forkhead box M1 (FOXM1) and HGF/Met signaling in promotion of PDA growth and resistance to Met inhibition was examined using cell culture, molecular biology and mouse models; and the relevance of our experimental and mechanistic findings were validated using human PDA tissues. Met was markedly overexpressed in both PDA cell lines and pancreatic tumor specimens, and the expression of Met correlated directly with that of FOXM1 in human tumor specimens. Mechanistically, FOXM1 bound to the promoter region of the Met gene and transcriptionally increased the expression of Met. Increased expression of FOXM1 enhanced the activation of HGF/Met signaling and its downstream pathways, including retrovirus-associated DNA sequences/extracellular signal-regulated kinase 1/2, phosphoinositide 3-kinase/AKT and signal transducer and activator of transcription 3. Furthermore, activation of HGF/Met signaling increased the expression and transcriptional activity of FOXM1, and the cross talk between FOXM1 and HGF/Met signaling promoted PDA growth and resistance to Met inhibition. Collectively, our findings identified a positive feedback loop formed by FOXM1 and HGF/Met and revealed that this loop is a potentially effective therapeutic target for PDA.

  8. Kisspeptin-10 inhibits cell migration in vitro via a receptor-GSK3 beta-FAK feedback loop in HTR8SVneo cells.

    PubMed

    Roseweir, A K; Katz, A A; Millar, R P

    2012-05-01

    Kisspeptin inhibits cancer cell metastasis and placental trophoblast cell migration. Kisspeptin gene expression in the placenta and circulating kisspeptin levels change during normal pregnancy and they are altered in preeclampsia. We therefore assessed the effect of kisspeptin-10 on the in vitro migration of a human placental cell line derived from first trimester extravillious trophoblasts (HTR8SVneo). HTR8SVneo cells specifically bound 125I-Kisspeptin-10 but kisspeptin-10 did not induce inositol phosphate production. Cell migration was inhibited by kisspeptin-10 with a maximal inhibition at 100nM. The signaling pathways involved in inhibition of cell migration were examined. Treatment with kisspeptin-10 elicited phosphorylation of GSK3 beta at Ser9 (which inhibits activity), with a 3-fold increase at 5 min. Transient phosphorylation of ERK1/2 and p38MAPK peaked at 10min. Phosphorylation of focal adhesion kinase (FAK) at Tyr925 increased 3-fold at 10 min. Inhibition of GSK3 beta correlated with release of beta-catenin into the cytoplasm. These signaling events were differentially blocked by inhibitors of G(q/11), Src, EGFR, PI(3)K, PKC and MEK. The data suggest that kisspeptin/GPR54 EGF-receptor transactivation leads to phosphorylation of ERK1/2, causing activation of p90rsk which in turn inhibits GSK3 beta via Ser9 phosphorylation. Inactivation of GSK3 beta results in release of beta-catenin into the cytoplasm, affecting cell-cell adhesion and Tyr925 phosphorylation of FAK, which increases phosphorylation of ERK1/2 via RAS/Raf-1 creating a feedback loop to enhance the effects on migration. These findings indicate that kisspeptin-10 inhibits the migration of human placental trophoblast-derived HTR8SVneo cells by stimulating complex ERK1/2-p90rsk-GSK3 beta-FAK feedback interactions.

  9. 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

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2014-01-01

    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

  12. Positive Feedback Loops for Factor V and Factor VII Activation Supply Sensitivity to Local Surface Tissue Factor Density During Blood Coagulation

    PubMed Central

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

    2011-01-01

    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/m2. 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/m2. 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. PMID:22004734

  13. 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

  14. Lnc-ATB contributes to gastric cancer growth through a MiR-141-3p/TGFβ2 feedback loop.

    PubMed

    Lei, Kecheng; Liang, Xin; Gao, Yuwei; Xu, Baixue; Xu, Yichun; Li, Yueqi; Tao, Yiwen; Shi, Weibin; Liu, Jianwen

    2017-03-11

    The long noncoding RNA (lncRNA) ATB is an important regulator in human tumors. Here, we aimed to investigate the potential molecular mechanisms of lnc-ATB in gastric cancer (GC) tumorigenesis. RT-qPCR analysis was used to detect lnc-ATB expression level in 20 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANTs). Moreover, the biological role of lnc-ATB was determined in vitro. We found that lnc-ATB was significantly upregulated in GC tissues compared to lnc-ATB expression in ANTs. These high lnc-ATB expression levels predicted poor prognosis in GC patients. Low levels of lnc-ATB inhibited GC cell proliferation and cell cycle arrest in vitro. Lnc-ATB was found to directly bind miR-141-3p. Moreover, TGF-β actives lnc-ATB and TGF-β2 directly binds mir-141-3p. Finally, we demonstrated that lnc-ATB fulfilled its oncogenic roles in a ceRNA-mediated manner. Our study suggests that lnc-ATB promotes tumor progression by interacting with miR-141-3p and that Lnc-ATB may be a valuable prognostic predictor for GC. In conclusion, the positive feedback loop of lnc-ATB/miR-141-3p/TGF-β2 may be a potential therapeutic target for the treatment of GC.

  15. Closed Loop Identification Based on the Virtual Reference Feedback Tuning Applied to a Virtual Two-Degree-of-Freedom Control System

    NASA Astrophysics Data System (ADS)

    Kaneko, Osamu; Beak, Yong Kawn; Ohtsuka, Toshiyuki

    A new identification method with respect to the parameter tuning of a controller is presented. Here, we introduce a virtual two-degree-of-freedom control structure with a feedforward controller described by using a mathematical model of a plant with a tunable parameter. After performing a one-shot experiment, we apply the virtual reference feedback tuning (VRFT), which is a rational and effective tuning method for the parameter of a controller with only one-shot experiment data, to a virtual feedforward controller by using the experimental data obtained in the actual closed loop. We give a condition for a prefilter which is applied to the data to guarantee that the obtained parameter using the VRFT of a controller is close to the desired one. We also show that the prefilter for the identification in the proposed method has a simpler form than that obtained in the normal VRFT for two-degree-of-freedom control scheme. Finally, in order to show the validity of the proposed method, we give an experimental result on the identification of the dynamics of the opening-closing speed of an elevator door.

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

    PubMed

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

    2015-10-06

    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.

  17. 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.

  18. Long non-coding RNA UCA1 enhances tamoxifen resistance in breast cancer cells through a miR-18a-HIF1α feedback regulatory loop.

    PubMed

    Li, Xiunan; Wu, Yumei; Liu, Aihui; Tang, Xin

    2016-11-01

    Recent studies reported that long non-coding RNAs (lncRNAs) might play critical roles in regulating endocrine resistance of breast cancer. Urothelial carcinoma-associated 1 (UCA1) is an lncRNA with an oncogenic role in breast cancer. This study aimed to investigate whether UCA1 is involved in acquired tamoxifen resistance in estrogen receptor (ER)-positive cancer cells. Our findings reveal that tamoxifen induces UCA1 upregulation in ER-positive breast cancer cells in a HIF1α-dependent manner. UCA1 upregulation results in significantly enhanced tamoxifen resistance. The upregulated UCA1 sponges miR-18a, which is a negative regulator of HIF1α. Therefore, UCA1 upregulation is further enhanced through a miR-18a-HIF1α feedback loop. In addition, our data also showed that miR-18a is a modulator of tamoxifen sensitivity due to its regulative effect on cell cycle proteins. miR-18a inhibitor reduced the sensitivity of MCF-7 cells to tamoxifen, while miR-18a mimics sensitized BT474 cells to tamoxifen. Therefore, miR-18a downregulation also partly contributes to acquired tamoxifen resistance in the cancer cells. These findings provide some useful information for future clinical treatment of tamoxifen resistance.

  19. 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

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

    PubMed

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

    2014-01-01

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

  1. Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer

    PubMed Central

    Hayakawa, Yoku; Hirata, Yoshihiro; Nakagawa, Hayato; Sakamoto, Kei; Hikiba, Yohko; Kinoshita, Hiroto; Nakata, Wachiko; Takahashi, Ryota; Tateishi, Keisuke; Tada, Motohisa; Akanuma, Masao; Yoshida, Haruhiko; Takeda, Kohsuke; Ichijo, Hidenori; Omata, Masao; Maeda, Shin; Koike, Kazuhiko

    2011-01-01

    Mitogen-activated protein kinase (MAPK) pathways regulate multiple cellular functions and are highly active in many types of human cancers. Apoptosis signal-regulating kinase 1 (ASK1) is an upstream MAPK involved in apoptosis, inflammation, and carcinogenesis. This study investigated the role of ASK1 in the development of gastric cancer. In human gastric cancer specimens, we observed increased ASK1 expression, compared to nontumor epithelium. Using a chemically induced murine gastric tumorigenesis model, we observed increased tumor ASK1 expression, and ASK1 knockout mice had both fewer and smaller tumors than wild-type (WT) mice. ASK1 siRNA inhibited cell proliferation through the accumulation of cells in G1 phase of the cell cycle, and reduced cyclin D1 expression in gastric cancer cells, whereas these effects were uncommon in other cancer cells. ASK1 overexpression induced the transcription of cyclin D1, through AP-1 activation, and ASK1 levels were regulated by cyclin D1, via the Rb–E2F pathway. Exogenous ASK1 induced cyclin D1 expression, followed by elevated expression of endogenous ASK1. These results indicate an autoregulatory mechanism of ASK1 in the development of gastric cancer. Targeting this positive feedback loop, ASK1 may present a potential therapeutic target for the treatment of advanced gastric cancer. PMID:21187402

  2. Application of the loop method for correcting acoustic doppler current profiler discharge measurements biased by sediment transport

    USGS Publications Warehouse

    Mueller, David S.; Wagner, Chad R.

    2006-01-01

    A systematic bias in discharge measurements made with an acoustic Doppler current profiler (ADCP) is attributed to the movement of sediment near the streambed-an issue widely acknowledged by the scientific community. This systematic bias leads to an underestimation of measured velocity and discharge. The integration of a differentially corrected Global Positioning System (DGPS) to track the movement of the ADCP can be used to avoid the systematic bias associated with a moving bed. DGPS systems, however, cannot provide consistently accurate positions because of multipath errors and satellite signal reception problems on waterways with dense tree canopy along the banks, in deep valleys or canyons, and near bridges. An alternative method of correcting for the moving-bed bias was investigated by the U.S. Geological Survey.

  3. Note: A frequency modulated wireless interrogation system exploiting narrowband acoustic resonator for remote physical quantity measurement

    NASA Astrophysics Data System (ADS)

    Droit, C.; Martin, G.; Ballandras, S.; Friedt, J.-M.

    2010-05-01

    We demonstrate the wireless conversion of frequency modulation to amplitude modulation by radio frequency resonators as means of accurately determining the resonance frequency of passive acoustoelectronic sensors. The emitted frequency modulated radio frequency pulses are generated by a pulsed radar for probing a surface acoustic wave based sensor. The sharp sign transition of the amplitude modulated received signal provides a signal on which a feedback loop is locked to monitor the resonance signal. The strategy is demonstrated using a full software implementation on a generic hardware, resulting in 2 Hz resolution at 1 s integration time limited by the proportional feedback loop.

  4. Note: A frequency modulated wireless interrogation system exploiting narrowband acoustic resonator for remote physical quantity measurement.

    PubMed

    Droit, C; Martin, G; Ballandras, S; Friedt, J-M

    2010-05-01

    We demonstrate the wireless conversion of frequency modulation to amplitude modulation by radio frequency resonators as means of accurately determining the resonance frequency of passive acoustoelectronic sensors. The emitted frequency modulated radio frequency pulses are generated by a pulsed radar for probing a surface acoustic wave based sensor. The sharp sign transition of the amplitude modulated received signal provides a signal on which a feedback loop is locked to monitor the resonance signal. The strategy is demonstrated using a full software implementation on a generic hardware, resulting in 2 Hz resolution at 1 s integration time limited by the proportional feedback loop.

  5. The hypoxia-inducible miR-429 regulates hypoxia-inducible factor-1α expression in human endothelial cells through a negative feedback loop

    PubMed Central

    Bartoszewska, Sylwia; Kochan, Kinga; Piotrowski, Arkadiusz; Kamysz, Wojciech; Ochocka, Renata J.; Collawn, James F.; Bartoszewski, Rafal

    2015-01-01

    Hypoxia-inducible factors (HIFs) 1 and 2 are dimeric α/β transcription factors that regulate cellular responses to low oxygen. HIF-1 is induced first, whereas HIF-2 is associated with chronic hypoxia. To determine how HIF1A mRNA, the inducible subunit of HIF-1, is regulated during hypoxia, we followed HIF1A mRNA levels in primary HUVECs over 24 hours using quantitative PCR. HIF1A and VEGF A (VEGFA) mRNA, a transcriptional target of HIF-1, increased ∼2.5- and 8-fold at 2–4 hours, respectively. To determine how the mRNAs were regulated, we identified a microRNA (miRNA), miR-429, that destabilized HIF1A message and decreased VEGFA mRNA by inhibiting HIF1A. Target protector analysis, which interferes with miRNA-mRNA complex formation, confirmed that miR-429 targeted HIF1A message. Desferoxamine treatment, which inhibits the hydroxylases that promote HIF-1α protein degradation, stabilized HIF-1 activity during normoxic conditions and elevated miR-429 levels, demonstrating that HIF-1 promotes miR-429 expression. RNA-sequencing-based transcriptome analysis indicated that inhibition of miRNA-429 in HUVECs up-regulated 209 mRNAs, a number of which regulate angiogenesis. The results demonstrate that HIF-1 is in a negative regulatory loop with miR-429, that miR-429 attenuates HIF-1 activity by decreasing HIF1A message during the early stages of hypoxia before HIF-2 is activated, and this regulatory network helps explain the HIF-1 transition to HIF-2 during chronic hypoxia in endothelial cells.—Bartoszewska, S., Kochan, K., Piotrowski, A., Kamysz, W., Ochocka, R. J., Collawn, J. F., Bartoszewski, R. The hypoxia-inducible miR-429 regulates hypoxia hypoxia-inducible factor-1α expression in human endothelial cells through a negative feedback loop. PMID:25550463

  6. Downregulation of COMMD1 by miR-205 promotes a positive feedback loop for amplifying inflammatory- and stemness-associated properties of cancer cells.

    PubMed

    Yeh, D-W; Chen, Y-S; Lai, C-Y; Liu, Y-L; Lu, C-H; Lo, J-F; Chen, L; Hsu, L-C; Luo, Y; Xiang, R; Chuang, T-H

    2016-05-01

    Sustained activation of nuclear factor-κB (NF-κB) in cancer cells has been shown to promote inflammation, expansion of cancer stem cell (CSC) population, and tumor development. In contrast, recent studies reveal that CSCs exhibit increased inflammation due to constitutive NF-κB activation; however, the underlying molecular mechanism remains unclear. In the present study, the analysis of microarray data revealed upregulation of NF-κB-regulated pro-inflammatory genes and downregulation of copper metabolism MURR1 domain-containing 1 (COMMD1) during the enrichment for stemness in SAS head and neck squamous-cell carcinoma (HNSCC) cells. The 3'-UTR of COMMD1 mRNA contains microRNA (miR)-205 target site. Parallel studies with HNSCC and NSCLC cells indicated that miR-205 is upregulated upon NF-κB activation and suppresses COMMD1 expression in stemness-enriched cancer cells. COMMD1 negatively regulates the inflammatory responses induced by TLR agonists, IL-1β, and TNF-α by targeting RelA for degradation. The shRNA-mediated downregulation of COMMD1 in cancer cells enhanced inflammatory response, generating favorable conditions for macrophage recruitment. In addition, genes associated with stemness were also upregulated in these cells, which exhibited increased potential for anchorage-independent growth. Furthermore, COMMD1 downregulation promoted in vivo tumorigenesis and tumor growth, and tumors derived from COMMD1-knockdown cells displayed elevated level of NF-κB activation, increased expression of inflammatory- and stemness-associated genes, and contain expanded population of tumor-associated leukocytes and stemness-enriched cancer cells. These results suggest that COMMD1 downregulation by miR-205 promotes tumor development by modulating a positive feedback loop that amplifies inflammatory- and stemness-associated properties of cancer cells.

  7. Adaptor protein CRK induces epithelial–mesenchymal transition and metastasis of bladder cancer cells through HGF/c-Met feedback loop

    PubMed Central

    Matsumoto, Ryuji; Tsuda, Masumi; Wang, Lei; Maishi, Nako; Abe, Takashige; Kimura, Taichi; Tanino, Mishie; Nishihara, Hiroshi; Hida, Kyoko; Ohba, Yusuke; Shinohara, Nobuo; Nonomura, Katsuya; Tanaka, Shinya

    2015-01-01

    We have previously reported that an adaptor protein CRK, including CRK-I and CRK-II, plays essential roles in the malignant potential of various aggressive human cancers, suggesting the validity of targeting CRK in molecular targeted therapy of a wide range of cancers. Nevertheless, the role of CRK in human bladder cancer with marked invasion, characterized by distant metastasis and poor prognosis, remains obscure. In the present study, immunohistochemistry indicated a striking enhancement of CRK-I/-II, but not CRK-like, in human bladder cancer tissues compared to normal urothelium. We established CRK-knockdown bladder cancer cells using 5637 and UM-UC-3, which showed a significant decline in cell migration, invasion, and proliferation. It is noteworthy that an elimination of CRK conferred suppressed phosphorylation of c-Met and the downstream scaffold protein Gab1 in a hepatocyte growth factor-dependent and -independent manner. In epithelial–mesenchymal transition-related molecules, E-cadherin was upregulated by CRK elimination, whereas N-cadherin, vimentin, and Zeb1 were downregulated. A similar effect was observed following treatment with c-Met inhibitor SU11274. Depletion of CRK significantly decreased cell proliferation of 5637 and UM-UC-3, consistent with reduced activity of ERK. An orthotopic xenograft model with bioluminescent imaging revealed that CRK knockdown significantly attenuated not only tumor volume but also the number of circulating tumor cells, resulted in a complete abrogation of metastasis. Taken together, this evidence uncovered essential roles of CRK in invasive bladder cancer through the hepatocyte growth factor/c-Met/CRK feedback loop for epithelial–mesenchymal transition induction. Thus, CRK might be a potent molecular target in bladder cancer, particularly for preventing metastasis, leading to the resolution of clinically longstanding critical issues. PMID:25816892

  8. 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

  9. E2F1-miR-20a-5p/20b-5p auto-regulatory feedback loop involved in myoblast proliferation and differentiation

    PubMed Central

    Luo, Wen; Li, Guihuan; Yi, Zhenhua; Nie, Qinghua; Zhang, Xiquan

    2016-01-01

    miR-17 family microRNAs (miRNAs) are crucial for embryo development, however, their role in muscle development is still unclear. miR-20a-5p and miR-20b-5p belong to the miR-17 family and are transcribed from the miR-17~92 and miR-106a~363 clusters respectively. In this study, we found that miR-20a-5p and miR-20b-5p promoted myoblast differentiation and repressed myoblast proliferation by directly binding the 3′ UTR of E2F transcription factor 1 (E2F1) mRNA. E2F1 is an important transcriptional factor for organism’s normal development. Overexpression of E2F1 in myoblasts promoted myoblast proliferation and inhibited myoblast differentiation. Conversely, E2F1 inhibition induced myoblast differentiation and repressed myoblast proliferation. Moreover, E2F1 can bind directly to promoters of the miR-17~92 and miR-106a~363 clusters and activate their transcription, and E2F1 protein expression is correlated with the expression of pri-miR-17~92 and pri-miR-106a~363 during myoblast differentiation. These results suggested an auto-regulatory feedback loop between E2F1 and miR-20a-5p/20b-5p, and indicated that miR-20a-5p, miR-20b-5p and E2F1 are involved in myoblast proliferation and differentiation through the auto-regulation between E2F1 and miR-20a-5p/20b-5p. These findings provide new insight into the mechanism of muscle differentiation, and further shed light on the understanding of muscle development and muscle diseases. PMID:27282946

  10. 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

    2016-08-15

    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.

  11. 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

  12. Aurora-A promotes the establishment of spindle assembly checkpoint by priming the Haspin-Aurora-B feedback loop in late G2 phase.

    PubMed

    Yu, Fazhi; Jiang, Ya; Lu, Lucy; Cao, Mimi; Qiao, Yulong; Liu, Xing; Liu, Dan; Van Dyke, Terry; Wang, Fangwei; Yao, Xuebiao; Guo, Jing; Yang, Zhenye

    2017-01-01

    Aurora-A kinase functions mainly in centrosome maturation, separation and spindle formation. It has also been found to be amplified or overexpressed in a range of solid tumors, which is linked with tumor progression and poor prognosis. Importantly, Aurora-A inhibitors are being studied in a number of ongoing clinical trials. However, whether and how Aurora-A has a role in the regulation of the mitotic checkpoint is controversial. Additionally, the function of nuclear-accumulated Aurora-A in late G2 phase is not clear. Here we show that knockout, inhibition or blockade of the nuclear entry of Aurora-A severely decreased the centromere localization of Aurora-B and the phosphorylation of histone H3 threonine 3 (H3T3-ph) mediated by the kinase Haspin in late G2 phase. We further reveal that nuclear-accumulated Aurora-A phosphorylates Haspin at multiple sites at its N-terminus and that this promotes H3T3-ph and the rapid recruitment to the centromere of the chromosomal passenger complex. In addition, Aurora-A facilitates the association of Aurora-B with their common substrates: Haspin and Plk1. Notably, these functions of Aurora-A are mostly independent of Plk1. Thus we demonstrate that, in late G2 and prophase, Aurora-A phosphorylates Haspin to trigger the Haspin-H3T3-ph-Aurora-B positive feedback loop that supports the timely establishment of the chromosomal passenger complex and the mitotic checkpoint before spindle assembly.

  13. A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation.

    PubMed

    Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song; Chen, Hungwen

    2016-01-01

    Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation.

  14. 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

  15. 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

  16. 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.

  17. Aurora-A promotes the establishment of spindle assembly checkpoint by priming the Haspin-Aurora-B feedback loop in late G2 phase

    PubMed Central

    Yu, Fazhi; Jiang, Ya; Lu, Lucy; Cao, Mimi; Qiao, Yulong; Liu, Xing; Liu, Dan; Van Dyke, Terry; Wang, Fangwei; Yao, Xuebiao; Guo, Jing; Yang, Zhenye

    2017-01-01

    Aurora-A kinase functions mainly in centrosome maturation, separation and spindle formation. It has also been found to be amplified or overexpressed in a range of solid tumors, which is linked with tumor progression and poor prognosis. Importantly, Aurora-A inhibitors are being studied in a number of ongoing clinical trials. However, whether and how Aurora-A has a role in the regulation of the mitotic checkpoint is controversial. Additionally, the function of nuclear-accumulated Aurora-A in late G2 phase is not clear. Here we show that knockout, inhibition or blockade of the nuclear entry of Aurora-A severely decreased the centromere localization of Aurora-B and the phosphorylation of histone H3 threonine 3 (H3T3-ph) mediated by the kinase Haspin in late G2 phase. We further reveal that nuclear-accumulated Aurora-A phosphorylates Haspin at multiple sites at its N-terminus and that this promotes H3T3-ph and the rapid recruitment to the centromere of the chromosomal passenger complex. In addition, Aurora-A facilitates the association of Aurora-B with their common substrates: Haspin and Plk1. Notably, these functions of Aurora-A are mostly independent of Plk1. Thus we demonstrate that, in late G2 and prophase, Aurora-A phosphorylates Haspin to trigger the Haspin-H3T3-ph-Aurora-B positive feedback loop that supports the timely establishment of the chromosomal passenger complex and the mitotic checkpoint before spindle assembly. PMID:28101375

  18. M2 macrophages induce ovarian cancer cell proliferation via a heparin binding epidermal growth factor/matrix metalloproteinase 9 intercellular feedback loop

    PubMed Central

    Carroll, Molly J.; Kapur, Arvinder; Felder, Mildred; Patankar, Manish S.; Kreeger, Pamela K.

    2016-01-01

    In ovarian cancer, a high ratio of anti-inflammatory M2 to pro-inflammatory M1 macrophages correlates with poor patient prognosis. The mechanisms driving poor tumor outcome as a result of the presence of M2 macrophages in the tumor microenvironment remain unclear and are challenging to study with current techniques. Therefore, in this study we utilized a micro-culture device previously developed by our lab to model concentrated paracrine signaling in order to address our hypothesis that interactions between M2 macrophages and ovarian cancer cells induce tumor cell proliferation. Using the micro-culture device, we determined that co-culture with M2-differentiated primary macrophages or THP-1 increased OVCA433 proliferation by 10–12%. This effect was eliminated with epidermal growth factor receptor (EGFR) or heparin-bound epidermal growth factor (HB-EGF) neutralizing antibodies and HBEGF expression in peripheral blood mononuclear cells from ovarian cancer patients was 9-fold higher than healthy individuals, suggesting a role for HB-EGF in tumor progression. However, addition of HB-EGF at levels secreted by macrophages or macrophage-conditioned media did not induce proliferation to the same extent, indicating a role for other factors in this process. Matrix metalloproteinase-9, MMP-9, which cleaves membrane-bound HB-EGF, was elevated in co-culture and its inhibition decreased proliferation. Utilizing inhibitors and siRNA against MMP9 in each population, we determined that macrophage-secreted MMP-9 released HB-EGF from macrophages, which increased MMP9 in OVCA433, resulting in a positive feedback loop to drive HB-EGF release and increase proliferation in co-culture. Identification of multi-cellular interactions such as this may provide insight into how to most effectively control ovarian cancer progression. PMID:27888810

  19. A novel AP-1/miR-101 regulatory feedback loop and its implication in the migration and invasion of hepatoma cells.

    PubMed

    Liu, Jing-Jing; Lin, Xue-Jia; Yang, Xiao-Jing; Zhou, Liangji; He, Shuai; Zhuang, Shi-Mei; Yang, Jine

    2014-10-29

    MicroRNA-101 (miR-101) is frequently downregulated in various cancers. To date, the regulatory networks of miR-101 remain obscure. In this study, we demonstrated that miR-101 was mainly transcribed from human miR-101-2 and mouse miR-101bgene loci. Subsequent analyses revealed that activator protein-1 (AP-1) directly binded to the -17.4 to -16.4 k region upstream of pre-miR-101-2 and activated the expression of miR-101. On the other hand, miR-101 could inhibit the expression of ERK2 and c-Fos, two key factors of the AP-1 pathway, by binding to their 3'-UTRs. Furthermore, reintroduction of miR-101 efficiently suppressed the AP-1 activity and pri-miR-101-2 transcription. These data thus suggest a novel AP-1/miR-101 regulatory circuitry, that is, AP-1 promotes the transcription of miR-101, whereas the expression of miR-101 reduces the level of ERK2 and c-Fos and thereby attenuates the AP-1 signaling. Further investigation disclosed that the AP-1 activator TPA-induced MMP9 activity and the TPA-promoted migration and invasion of hepatoma cells were significantly attenuated by miR-101 but were enhanced by miR-101 inhibitor. Our results suggest that the AP-1/miR-101 feedback loop may prevent the excessive activation of metastatic signals imposed by ERK2/AP-1 and highlight the biological significance of miR-101 downregulation in cancer metastasis.

  20. miR-223 Regulates Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells Through a C/EBPs/miR-223/FGFR2 Regulatory Feedback Loop.

    PubMed

    Guan, Xiaohui; Gao, Yifei; Zhou, Jie; Wang, Jun; Zheng, Fang; Guo, Fei; Chang, Ailing; Li, Xiaoxia; Wang, Baoli

    2015-05-01

    Several miRNAs have recently been identified to regulate adipocyte or osteoblast differentiation or both. In this study, miR-223 was found to be involved in the reciprocal regulation of adipocyte and osteoblast differentiation. miR-223 was induced in primary cultured mouse marrow stromal cell, mesenchymal line C3H10T1/2 and stromal line ST2 after adipogenic treatment. Conversely, it was reduced in preosteoblast MC3T3-E1 after osteogenic treatment. Supplementing miR-223 levels using synthetic miR-223 mimics significantly suppressed the growth of the C3H10T1/2 and ST2 cells and induced the progenitor cells to fully differentiate into adipocytes, along with induction of adipocyte-specific transcription factors peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein-α (C/EBPα), and marker genes aP2 and adipsin. By contrast, depletion of the endogenous miR-223 using synthetic miR-223 inhibitor repressed the progenitor cells to differentiate. The effects of miR-223 on adipocyte formation from ST2 cells were also demonstrated by using lentivirus that overexpresses miR-223. Conversely, supplementing miR-223 blocked ST2 to differentiate into osteoblasts. Fibroblast growth factor receptor 2 (Fgfr2), a critical regulator of osteoblast, was shown to be a direct target of miR-223 by using dual luciferase reporter assay. Knockdown of Fgfr2 in C3H10T1/2 downregulated phosphorylation of ERK1/2 and upregulated expression of C/EBPα and dramatically enhanced the differentiation of the cells into adipocytes. Further investigation of mechanisms that control miR-223 expression demonstrated that C/EBPs induced miR-223 expression through binding to the promoter regions of the miR-223. Taken together, our study provides evidences that miR-223 regulates adipocyte and osteoblast differentiation through a novel C/EBPs/miR-223/FGFR2 regulatory feedback loop.

  1. Evidence Favoring a Positive Feedback Loop for Physiologic Auto Upregulation of hnRNP-E1 during Prolonged Folate Deficiency in Human Placental Cells.

    PubMed

    Tang, Ying-Sheng; Khan, Rehana A; Xiao, Suhong; Hansen, Deborah K; Stabler, Sally P; Kusumanchi, Praveen; Jayaram, Hiremagalur N; Antony, Aśok C

    2017-04-01

    and folate receptors in cultured human cells and tumor xenografts, and more selectively in various fetal tissues of folate-deficient dams.Conclusions: This novel positive feedback loop amplifies hnRNP-E1 during prolonged folate deficiency and thereby maximizes upregulation of folate receptors in order to restore folate homeostasis toward normalcy in placental cells. It will also functionally impact several other mRNAs of the nutrition-sensitive, folate-responsive posttranscriptional RNA operon that is orchestrated by homocysteinylated hnRNP-E1.

  2. Let-7b/c enhance the stability of a tissue-specific mRNA during mammalian organogenesis as part of a feedback loop involving KSRP.

    PubMed

    Repetto, Emanuela; Briata, Paola; Kuziner, Nathalie; Harfe, Brian D; McManus, Michael T; Gherzi, Roberto; Rosenfeld, Michael G; Trabucchi, Michele

    2012-01-01

    Gene silencing mediated by either microRNAs (miRNAs) or Adenylate/uridylate-rich elements Mediated mRNA Degradation (AMD) is a powerful way to post-transcriptionally modulate gene expression. We and others have reported that the RNA-binding protein KSRP favors the biogenesis of select miRNAs (including let-7 family) and activates AMD promoting the decay of inherently labile mRNAs. Different layers of interplay between miRNA- and AMD-mediated gene silencing have been proposed in cultured cells, but the relationship between the two pathways in living organisms is still elusive. We conditionally deleted Dicer in mouse pituitary from embryonic day (E) 9.5 through Cre-mediated recombination. In situ hybridization, immunohistochemistry, and quantitative reverse transcriptase-PCR revealed that Dicer is essential for pituitary morphogenesis and correct expression of hormones. Strikingly, αGSU (alpha glycoprotein subunit, common to three pituitary hormones) was absent in Dicer-deleted pituitaries. αGSU mRNA is unstable and its half-life increases during pituitary development. A transcriptome-wide analysis of microdissected E12.5 pituitaries revealed a significant increment of KSRP expression in conditional Dicer-deleted mice. We found that KSRP directly binds to αGSU mRNA, promoting its rapid decay; and, during pituitary development, αGSU expression displays an inverse temporal relationship to KSRP. Further, let-7b/c downregulated KSRP expression, promoting the degradation of its mRNA by directly binding to the 3'UTR. Therefore, we propose a model in which let-7b/c and KSRP operate within a negative feedback loop. Starting from E12.5, KSRP induces the maturation of let-7b/c that, in turn, post-transcriptionally downregulates the expression of KSRP itself. This event leads to stabilization of αGSU mRNA, which ultimately enhances the steady-state expression levels. We have identified a post-transcriptional regulatory network active during mouse pituitary development in

  3. Amplification of Reynolds number dependent processes by wave distortion. [acoustic instability of liquid propellant rocket engines

    NASA Technical Reports Server (NTRS)

    Ventrice, M. B.; Fang, J. C.; Purdy, K. R.

    1975-01-01

    A system using a hot-wire transducer as an analog of a liquid droplet of propellant was employed to investigate the ingredients of the acoustic instability of liquid-propellant rocket engines. It was assumed that the combustion process was vaporization-limited and that the combustion chamber was acoustically similar to a closed-closed right-circular cylinder. Before studying the hot-wire closed-loop system (the analog system), a microphone closed-loop system, which used the response of a microphone as the source of a linear feedback exciting signal, was investigated to establish the characteristics of self-sustenance of acoustic fields. Self-sustained acoustic fields were found to occur only at resonant frequencies of the chamber. In the hot-wire closed-loop system, the response of hot-wire anemometer was used as the source of the feedback exciting signal. The self-sustained acoustic fields which developed in the system were always found to be harmonically distorted and to have as their fundamental frquency a resonant frequency for which there also existed a second resonant frequency which was approximately twice the fundamental frequency.

  4. Convolution feedback systems.

    NASA Technical Reports Server (NTRS)

    Desoer, C. A.; Callier, F. M.

    1972-01-01

    Linear time-invariant feedback systems with multiple inputs and multiple outputs are examined. It is demonstrated that no loss of generality takes place considering the feedback to be unity. Necessary and sufficient conditions are derived for the closed-loop impulse response to be stable in a prescribed sense.

  5. 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.

  6. Active cancellation of acoustical resonances with an FPGA FIR filter.

    PubMed

    Ryou, Albert; Simon, Jonathan

    2017-01-01

    We present a novel approach to enhancing the bandwidth of a feedback-controlled mechanical system by digitally canceling acoustical resonances (poles) and anti-resonances (zeros) in the open-loop response via an FPGA FIR filter. By performing a real-time convolution of the feedback error signal with an inverse filter, we can suppress arbitrarily many poles and zeros below 100 kHz, each with a linewidth down to 10 Hz. We demonstrate the efficacy of this technique by canceling the ten largest mechanical resonances and anti-resonances of a high-finesse optical resonator, thereby enhancing the unity gain frequency by more than an order of magnitude. This approach is applicable to a broad array of stabilization problems including optical resonators, external cavity diode lasers, and scanning tunneling microscopes and points the way to applying modern optimal control techniques to intricate linear acoustical systems.

  7. 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.

  8. Development of a GaAs Monolithic Surface Acoustic Wave Integrated Circuit

    SciTech Connect

    Baca, A.G.; Casalnuovo, S.C.; Drummond, T.J.; Frye, G.C.; Heller, E.J.; Hietala, V.M.; Klem, J.F.

    1999-03-08

    An oscillator technology using surface acoustic wave delay lines integrated with GaAs MESFET electronics has been developed for GaAs-based integrated microsensor applications. The oscillator consists of a two-port SAW delay line in a feedback loop with a four-stage GaAs MESFET amplifier. Oscillators with frequencies of 470, 350, and 200 MHz have been designed and fabricated. These oscillators are also promising for other RF applications.

  9. The effect of acoustic forcing on an airfoil tonal noise mechanism.

    PubMed

    Schumacher, Karn L; Doolan, Con J; Kelso, Richard M

    2014-08-01

    The response of the boundary layer over an airfoil with cavity to external acoustic forcing, across a sweep of frequencies, was measured. The boundary layer downstream of the cavity trailing edge was found to respond strongly and selectively at the natural airfoil tonal frequencies. This is considered to be due to enhanced feedback. However, the shear layer upstream of the cavity trailing edge did not respond at these frequencies. These findings confirm that an aeroacoustic feedback loop exists between the airfoil trailing edge and a location near the cavity trailing edge.

  10. 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.

  11. Acoustic Translation of an Acoustically Levitated Sample

    NASA Technical Reports Server (NTRS)

    Barmatz, M. B.; Allen, J. L.

    1986-01-01

    Acoustic-levitation apparatus uses only one acoustic mode to move sample from one region of chamber to another. Sample heated and cooled quickly by translation between hot and cold regions of levitation chamber. Levitated sample is raised into furnace region by raising plunger. Frequency of sound produced by transducers adjusted by feedback system to maintain (102) resonant mode, which levitates sample midway between transducers and plunger regardless of plunger position.

  12. 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

  13. Regulation of the ErbB network by the MIG6 feedback loop in physiology, tumor suppression and responses to oncogene-targeted therapeutics.

    PubMed

    Anastasi, Sergio; Lamberti, Dante; Alemà, Stefano; Segatto, Oreste

    2016-02-01

    The ErbB signaling network instructs the execution of key cellular programs, such as cell survival, proliferation and motility, through the generation of robust signals of defined strength and duration. In contrast, unabated ErbB signaling disrupts tissue homeostasis and leads to cell transformation. Cells oppose the threat inherent in excessive ErbB activity through several mechanisms of negative feedback regulation. Inducible feedback inhibitors (IFIs) are expressed in the context of transcriptional responses triggered by ErbB signaling, thus being uniquely suited to regulate ErbB activity during the execution of complex cellular programs. This review focuses on MIG6, an IFI that restrains ErbB signaling by mediating ErbB kinase suppression and receptor down-regulation. We will review key issues in MIG6 function, regulation and tumor suppressor activity. Subsequently, the role for MIG6 loss in the pathogenesis of tumors driven by ErbB oncogenes as well as in the generation of cellular addiction to ErbB signaling will be discussed. We will conclude by analyzing feedback inhibition by MIG6 in the context of therapies directed against ErbB and non-ErbB oncogenes.

  14. Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-α in myocardial infarction-induced cardiac fibrosis

    PubMed Central

    Li, Chunmei; Han, Rui; Kang, Le; Wang, Jianping; Gao, Yonglin; Li, Yanshen; He, Jie; Tian, Jingwei

    2017-01-01

    Pirfenidone (PFD), an anti-fibrotic small molecule drug, is used to treat fibrotic diseases, but its effects on myocardial infarction (MI)-induced cardiac fibrosis are unknown. The aim of this study was to determine the effects of PFD on MI-induced cardiac fibrosis and the possible underlying mechanisms in rats. After establishment of the model, animals were administered PFD by gavage for 4 weeks. During the development of MI-induced cardiac fibrosis, we found activation of a positive feedback loop between the angiotensin II type 1 receptor (AT1R)/phospho-p38 mitogen-activated protein kinase (p38 MAPK) pathway and renin-angiotensin system (RAS), which was accompanied by down-regulation of liver X receptor-α (LXR-α) expression. PFD attenuated body weight, heart weight, left ventricular weight, left ventricular systolic pressure, and ±dp/dtmax changes induced by MI, which were associated with a reduction in cardiac fibrosis, infarct size, and hydroxyproline concentration. Moreover, PFD inhibited the AT1R/p38 MAPK pathway, corrected the RAS imbalance [decreased angiotensin-converting enzyme (ACE), angiotensin II, and angiotensin II type 1 receptor expression, but increased ACE2 and angiotensin (1-7) activity and Mas expression] and strongly enhanced heart LXR-α expression. These results indicate that the cardioprotective effects of PFD may be due, in large part, to controlling the feedback loop of the AT1R/p38 MAPK/RAS axis by activation of LXR-α. PMID:28091615

  15. 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…

  16. 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.

  17. The ZEB1 Transcription Factor Acts in a Negative Feedback Loop with miR200 Downstream of Ras and Rb1 to Regulate Bmi1 Expression*

    PubMed Central

    Liu, Yongqing; Sánchez-Tilló, Ester; Lu, Xiaoqin; Huang, Li; Clem, Brian; Telang, Sucheta; Jenson, Alfred B.; Cuatrecasas, Miriam; Chesney, Jason; Postigo, Antonio; Dean, Douglas C.

    2014-01-01

    Ras mutations are frequent in cancer cells where they drive proliferation and resistance to apoptosis. However in primary cells, mutant Ras instead can cause oncogene-induced senescence, a tumor suppressor function linked to repression of the polycomb factor Bmi1, which normally regulates cell cycle inhibitory cyclin-dependent kinase inhibitors (cdki). It is unclear how Ras causes repression of Bmi1 in primary cells to suppress tumor formation while inducing the gene in cancer cells to drive tumor progression. Ras also induces the EMT transcription factor ZEB1 to trigger tumor invasion and metastasis. Beyond its well-documented role in EMT, ZEB1 is important for maintaining repression of cdki. Indeed, heterozygous mutation of ZEB1 is sufficient for elevated cdki expression, leading to premature senescence of primary cells. A similar phenotype is evident with Bmi1 mutation. We show that activation of Rb1 in response to mutant Ras causes dominant repression of ZEB1 in primary cells, but loss of the Rb1 pathway is a hallmark of cancer cells and in the absence of such Rb1 repression Ras induces ZEB1 in cancer cells. ZEB1 represses miR-200 in the context of a mutual repression loop. Because miR-200 represses Bmi1, induction of ZEB1 leads to induction of Bmi1. Rb1 pathway status then dictates the opposing effects of mutant Ras on the ZEB1-miR-200 loop in primary versus cancer cells. This loop not only triggers EMT, surprisingly we show it acts downstream of Ras to regulate Bmi1 expression and thus the critical decision between oncogene-induced senescence and tumor initiation. PMID:24371144

  18. A prototype framework for models of socio-hydrology: identification of key feedback loops with application to two Australian case-studies

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

    It is increasingly acknowledged that, in order to sustainably manage global freshwater resources, it is critical that we better understand the nature of human-hydrology interactions at the broader catchment system-scale. Yet to date, a generic conceptual framework for building models of catchment systems that include adequate representation of socioeconomic systems - and the dynamic feedbacks between human and natural systems - has remained elusive. In an attempt to work towards such a model, this paper outlines a generic framework for a model of socio-hydrology that posits a novel construct, a composite Community Sensitivity state variable, as a key link to elucidate the drivers of behavioural response in a hydrological context. The framework provides for both macro-scale contextual parameters, which allow it to be applied across climate, socioeconomic and political gradients, and catchment-specific conditions, by way of tailored "closure relationships", in order to ensure that site-specific and application-specific contexts of socio-hydrologic problems can be accommodated. To demonstrate how such a framework would be applied, two different socio-hydrological case studies, taken from the Australian experience, are presented and discussed. It is envisioned that the application of this framework across study sites and gradients will aid in developing our understanding of the fundamental interactions and feedbacks in such complex human-hydrology systems, and allow hydrologists to participate in the growing field of social-ecological systems modelling.

  19. 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…

  20. Acoustic neuroma

    MedlinePlus

    Vestibular schwannoma; Tumor - acoustic; Cerebellopontine angle tumor; Angle tumor; Hearing loss - acoustic; Tinnitus - acoustic ... Acoustic neuromas have been linked with the genetic disorder neurofibromatosis type 2 (NF2). Acoustic neuromas are uncommon.

  1. 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.

  2. 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.

  3. A positive feedback loop between HER2 and ADAM12 in human head and neck cancer cells increases migration and invasion.

    PubMed

    Rao, V H; Kandel, A; Lynch, D; Pena, Z; Marwaha, N; Deng, C; Watson, P; Hansen, L A

    2012-06-07

    Increased activation of epidermal growth factor receptor (EGFR) family members such as HER2/Erbb2 can result in more aggressive disease, resistance to chemotherapy and reduced survival of head and neck squamous cell carcinoma (HNSCC) patients. In order to identify mechanisms through which these receptor tyrosine kinases accelerate tumor progression, the regulation of metalloprotease expression by EGFR family members was investigated in 11 squamous cell carcinoma (SCC) cell lines. HER2 expression was significantly correlated with ADAM12 (A Disintegrin And Metalloprotease 12) expression in these cell lines and was co-expressed in human head and neck cancers. Inhibition of HER2 or EGFR decreased ADAM12 transcripts whereas HER2 transfection upregulated ADAM12 expression. To understand the molecular mechanisms underlying HER2 regulation of ADAM12, we investigated the signaling pathways directing ADAM12 production in SCC cells. Inhibition of phosphatidyl inositol-3-kinase or mammalian target of rapamycin decreased ADAM12 transcripts in HER2-expressing SCC cells, whereas transfection with AKT increased ADAM12 mRNA. Experiments utilizing ADAM12 transfection or siRNA targeting of ADAM12 revealed that the protease increased both the migration and invasiveness of oral SCC cells. Surprisingly, ADAM12 also increased HER2 message, protein levels and activity through an Ets1-dependent mechanism. Collectively, these results reveal a novel positive activation loop between ADAM12 and HER2 that may contribute to HNSCC progression.

  4. Epigenetically deregulated microRNA-375 is involved in a positive feedback loop with estrogen receptor alpha in breast cancer cells.

    PubMed

    de Souza Rocha Simonini, Pedro; Breiling, Achim; Gupta, Nibedita; Malekpour, Mahdi; Youns, Mahmoud; Omranipour, Ramesh; Malekpour, Fatemeh; Volinia, Stefano; Croce, Carlo M; Najmabadi, Hossein; Diederichs, Sven; Sahin, Ozgür; Mayer, Doris; Lyko, Frank; Hoheisel, Jörg D; Riazalhosseini, Yasser

    2010-11-15

    Estrogen receptor α (ERα) upregulation causes abnormal cell proliferation in about two thirds of breast cancers, yet understanding of the underlying mechanisms remains incomplete. Here, we show that high expression of the microRNA miR-375 in ERα-positive breast cell lines is a key driver of their proliferation. miR-375 overexpression was caused by loss of epigenetic marks including H3K9me2 and local DNA hypomethylation, dissociation of the transcriptional repressor CTCF from the miR-375 promoter, and interactions of ERα with regulatory regions of miR-375. Inhibiting miR-375 in ERα-positive MCF-7 cells resulted in reduced ERα activation and cell proliferation. A combination of expression profiling from tumor samples and miRNA target prediction identified RASD1 as a potential miR-375 target. Mechanistic investigations revealed that miR-375 regulates RASD1 by targeting the 3' untranslated region in RASD1 mRNA. Additionally, we found that RASD1 negatively regulates ERα expression. Our findings define a forward feedback pathway in control of ERα expression, highlighting new strategies to treat ERα-positive invasive breast tumors.

  5. 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.

  6. Feedback characteristics between implantable microphone and transducer in middle ear cavity.

    PubMed

    Arman Woo, S H; Woo, Seong Tak; Song, Byung Seop; Cho, Jin-Ho

    2013-10-01

    With the advent of implantable hearing aids, implementation and acoustic sensing strategy of the implantable microphone becomes an important issue; among the many types of implantable microphone, placing the microphone in middle ear cavity (MEC) has advantages including simple operation and insensitive to skin touching or chewing motion. In this paper, an implantable microphone was implemented and researched feedback characteristic when both the implantable microphone and the transducer were placed in the MEC. Analytical and finite element analysis were conducted to design the microphone to have a natural frequency of 7 kHz and showed good characteristics of SNR and sensitivity. For the feedback test, simple analytical and finite element analysis were calculated and compared with in vitro experiments (n = 4). From the experiments, the open-loop gain and feedback factor were measured and the minimum gain margin measured as 14.3 dB.

  7. Loop quantization

    SciTech Connect

    Nicolau, A.

    1988-10-01

    Loop unwinding is a known technique for reducing loop overhead, exposing parallelism, and increasing the efficiency of pipelining. Traditional loop unwinding is limited to the innermost loop in a group of nested loops and the amount of unwinding either is fixed or must be specified by the user, on a case by case basis. In this paper the authors present a general technique for automatically unwinding multiply nested loops, explain its advantages over other transformation techniques, and illustrate its practical effectiveness. Lopp Quantization could be beneficial by itself or coupled with other loop transformations.

  8. Learning to pronounce Vowel Sounds in a Foreign Language Using Acoustic Measurements of the Vocal Tract as Feedback in Real Time.

    ERIC Educational Resources Information Center

    Dowd, Annette; Smith, John; Wolfe, Joe

    1998-01-01

    Measured the first two vowel-tract resonances of a sample of native-French speakers for the non-nasalized vowels of that language. Values measured for native speakers for a particular vowel were used as target parameters for subjects who used a visual display of an impedance spectrum of their own vocal tracts as real time feedback to realize the…

  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

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

    2016-04-05

    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.

  10. A direct current superconducting quantum interference device gradiometer with a digital signal processor controlled flux-locked loop and comparison with a conventional analog feedback scheme

    SciTech Connect

    Kung, P.J.; Bracht, R.R.; Flynn, E.R.; Lewis, P.S.

    1996-01-01

    A double-washer dc superconducting quantum interference device (SQUID) gradiometer with a flux-locked loop (FLL) based on a digital signal processor (DSP) has been developed for biomagnetic applications. All of the analog electronics in the conventional FLL are replaced and implemented by the DSP except for the low-noise field-effect transistor preamplifier at the front end of the signal recovery components. The DSP performs the signal demodulation by synchronously sampling the recovered signals and applying the appropriate full wave rectification. The signals are then integrated, filtered, and applied to the output. At 4.2 K, the white flux noise of the gradiometer measured in a DSP FLL mode is about 4{mu}{phi}{sub 0}/{radical}Hz and the noise at 1 Hz is 13 {mu}{phi}{sub 0}/{radical}Hz. The corresponding noise levels in the gradiometer operated by the conventional FLL are 1.8 and 3{mu}{phi}{sub 0}/{radical}Hz. The poorer system performance in the DSP FLL compared to the analog FLL is mainly caused by the ambient field noise and interference signals picked up through the connecting cables. Additional noise is also added to the overall noise floor by the instruments employed in the DSP system in the present prototype setup. Further improvement in the noise characteristics and the dynamic behavior of the DSP SQUID gradiometer is expected when a better configuration of DSP with the associated I/O devices is implemented. Additional improvements of the DSP programs are expected by incorporating higher-order integration, adaptive control, and noise reduction schemes. {copyright} {ital 1996 American Institute of Physics.}

  11. Growth factor TGF-β induces intestinal epithelial cell (IEC-6) differentiation: miR-146b as a regulatory component in the negative feedback loop.

    PubMed

    Liao, Yalin; Zhang, Man; Lönnerdal, Bo

    2013-01-01

    TGF-β is a potent pleiotropic factor that promotes small intestinal cell differentiation. The role of microRNAs in the TGF-β induction of intestinal epithelial phenotype is largely unknown. We hypothesized that microRNAs are functionally involved in TGF-β-induced intestinal cell growth. In this study, TGF-β caused a morphological change of IEC-6 cells and stimulated expression of the epithelial cell markers alkaline phosphatase, villin, and aminopeptidase N. By global microRNA profiling during TGF-β-induced intestinal crypt cell (IEC-6) differentiation, we identified 19 differentially expressed microRNAs. We showed by real-time Q-PCR that miR-146b expression increased rapidly after TGF-β treatment; sequence analysis and in vitro assays revealed that miR-146b targets SIAH2, an E3 ubiquitin ligase, with decreased protein expression upon IEC-6 cell differentiation. Transfection of miR-146b inhibitor before TGF-β treatment blocked the down-regulation of SIAH2 in response to TGF-β. Moreover, SIAH2 over-expression during TGF-β treatment caused a significant decrease in Smad7 protein expression in IEC-6 cells. Furthermore, activation of the ERK1/2 pathway is active in the up-regulation of miR-146b by TGF-β. These findings suggest a novel mechanism whereby TGF-β signaling during IEC-6 cell differentiation may be modulated in part by microRNAs, and we propose a key role for miR-146b in the homeostasis of growth factor TGF-β signaling through a negative feedback regulation involving down-regulation of SIAH2 repressed Smad7 activities.

  12. A double-negative feedback loop between Wnt-β-catenin signaling and HNF4α regulates epithelial-mesenchymal transition in hepatocellular carcinoma.

    PubMed

    Yang, Meng; Li, Sheng-Nan; Anjum, Khalid M; Gui, Long-Xin; Zhu, Shan-Shan; Liu, Jun; Chen, Jia-Kun; Liu, Qing-Feng; Ye, Guo-Dong; Wang, Wen-Jie; Wu, Jia-Fa; Cai, Wang-Yu; Sun, Guang-Bin; Liu, Yun-Jia; Liu, Rong-Fu; Zhang, Zhi-Ming; Li, Bo-An

    2013-12-15

    Wnt-β-catenin signaling participates in the epithelial-mesenchymal transition (EMT) in a variety of cancers; however, its involvement in hepatocellular carcinoma (HCC) and downstream molecular events is largely undefined. HNF4α is the most prominent and specific factor maintaining the differentiation of hepatic lineage cells and a potential EMT regulator in HCC cells. However, the molecular mechanisms by which HNF4α maintains the differentiated liver epithelium and inhibits EMT have not been completely defined. In this study, we systematically explored the relationship between Wnt-β-catenin signaling and HNF4α in the EMT process of HCC cells. Our results indicated that HNF4α expression was negatively regulated during Wnt-β-catenin signaling-induced EMT through Snail and Slug in HCC cells. In contrast, HNF4α was found to directly associate with TCF4 to compete with β-catenin but facilitate transcription co-repressor activities, thus inhibiting expression of EMT-related Wnt-β-catenin targets. Moreover, HNF4α may control the switch between the transcriptional and adhesion functions of β-catenin. Overexpression of HNF4α was found to completely compromise the Wnt-β-catenin-signaling-induced EMT phenotype. Finally, we determined the regulation pattern between Wnt-β-catenin signaling and HNF4α in rat tumor models. Our studies have identified a double-negative feedback mechanism controlling Wnt-β-catenin signaling and HNF4α expression in vitro and in vivo, which sheds new light on the regulation of EMT in HCC. The modulation of these molecular processes may be a method of inhibiting HCC invasion by blocking Wnt-β-catenin signaling or restoring HNF4α expression to prevent EMT.

  13. Direct Field Acoustic Testing

    NASA Technical Reports Server (NTRS)

    Larkin, Paul; Goldstein, Bob

    2008-01-01

    This paper presents an update to the methods and procedures used in Direct Field Acoustic Testing (DFAT). The paper will discuss some of the recent techniques and developments that are currently being used and the future publication of a reference standard. Acoustic testing using commercial sound system components is becoming a popular and cost effective way of generating a required acoustic test environment both in and out of a reverberant chamber. This paper will present the DFAT test method, the usual setup and procedure and the development and use of a closed-loop, narrow-band control system. Narrow-band control of the acoustic PSD allows all standard techniques and procedures currently used in random control to be applied to acoustics and some examples are given. The paper will conclude with a summary of the development of a standard practice guideline that is hoped to be available in the first quarter of next year.

  14. Spacecraft Internal Acoustic Environment Modeling

    NASA Technical Reports Server (NTRS)

    Chu, S. Reynold; Allen, Chris

    2009-01-01

    The objective of the project is to develop an acoustic modeling capability, based on commercial off-the-shelf software, to be used as a tool for oversight of the future manned Constellation vehicles. The use of such a model will help ensure compliance with acoustic requirements. Also, this project includes modeling validation and development feedback via building physical mockups and conducting acoustic measurements to compare with the predictions.

  15. A Positive Feedback Loop Links Opposing Functions of P-TEFb/Cdk9 and Histone H2B Ubiquitylation to Regulate Transcript Elongation in Fission Yeast

    PubMed Central

    Jacques, Pierre-Étienne; Pagé, Viviane; Nagy, Stephen; Racine, Ariane; St. Amour, Courtney V.; Zhang, Chao; Shokat, Kevan M.; Schwer, Beate; Robert, François; Fisher, Robert P.; Tanny, Jason C.

    2012-01-01

    Transcript elongation by RNA polymerase II (RNAPII) is accompanied by conserved patterns of histone modification. Whereas histone modifications have established roles in transcription initiation, their functions during elongation are not understood. Mono-ubiquitylation of histone H2B (H2Bub1) plays a key role in coordinating co-transcriptional histone modification by promoting site-specific methylation of histone H3. H2Bub1 also regulates gene expression through an unidentified, methylation-independent mechanism. Here we reveal bidirectional communication between H2Bub1 and Cdk9, the ortholog of metazoan positive transcription elongation factor b (P-TEFb), in the fission yeast Schizosaccharomyces pombe. Chemical and classical genetic analyses indicate that lowering Cdk9 activity or preventing phosphorylation of its substrate, the transcription processivity factor Spt5, reduces H2Bub1 in vivo. Conversely, mutations in the H2Bub1 pathway impair Cdk9 recruitment to chromatin and decrease Spt5 phosphorylation. Moreover, an Spt5 phosphorylation-site mutation, combined with deletion of the histone H3 Lys4 methyltransferase Set1, phenocopies morphologic and growth defects due to H2Bub1 loss, suggesting independent, partially redundant roles for Cdk9 and Set1 downstream of H2Bub1. Surprisingly, mutation of the histone H2B ubiquitin-acceptor residue relaxes the Cdk9 activity requirement in vivo, and cdk9 mutations suppress cell-morphology defects in H2Bub1-deficient strains. Genome-wide analyses by chromatin immunoprecipitation also demonstrate opposing effects of Cdk9 and H2Bub1 on distribution of transcribing RNAPII. Therefore, whereas mutual dependence of H2Bub1 and Spt5 phosphorylation indicates positive feedback, mutual suppression by cdk9 and H2Bub1-pathway mutations suggests antagonistic functions that must be kept in balance to regulate elongation. Loss of H2Bub1 disrupts that balance and leads to deranged gene expression and aberrant cell morphologies, revealing a

  16. 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.

  17. Feedback & Objectives

    ERIC Educational Resources Information Center

    Butterworth, James R.

    1975-01-01

    Industrial objectives, if they are employee oriented, produce feedback, and the motivation derived from the feedback helps reduce turnover. Feedback is the power to clarify objectives, to stimulate communication, and to motivate people. (Author/MW)

  18. 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

  19. MiR-21 modulates radiosensitivity of cervical cancer through inhibiting autophagy via the PTEN/Akt/HIF-1α feedback loop and the Akt-mTOR signaling pathway.

    PubMed

    Song, Lili; Liu, Shikai; Zhang, Liang; Yao, Hairong; Gao, Fangyuan; Xu, Dongkui; Li, Qian

    2016-09-01

    MiR-21 is an important microRNA (miRNA) modulating radiosensitivity of cervical cancer cells. However, the underlying mechanism of miR-21 upregulation in radioresistant cervical cancer has not been fully understood. In addition, autophagy may either promote or alleviate radioresistance, depending on the types of cancer and tumor microenvironment. How autophagy affects radiosensitivity in cervical cancer and how miR-21 is involved in this process has not been reported. This study showed that miR-21 upregulation in radioresistant cervical cancer is related to HIF-1α overexpression. MiR-21 overexpression decreases PTEN, increases p-Akt, and subsequently increases HIF-1α expression, while miR-21 inhibition results in increased PTEN, decreased p-Akt, and then decreased HIF-1α. Therefore, we inferred that there is a HIF-1α-miR-21 positive feedback loop through the PTEN/Akt/HIF-1α pathway in cervical cancer cells. In addition, we also demonstrated that miR-21 confers decreased autophagy in cervical cancer cells after IR via the Akt-mTOR signaling pathway. Decreased autophagy is one of the potential mechanisms of increased radioresistance in cervical cancer cells. These findings expand our understanding of radioresistance development in cervical cancer.

  20. 3B, a novel photosensitizer, inhibits glycolysis and inflammation via miR-155-5p and breaks the JAK/STAT3/SOCS1 feedback loop in human breast cancer cells.

    PubMed

    Lei, Kecheng; Du, Wenpei; Lin, Shengchao; Yang, Liyan; Xu, Yichun; Gao, Yuwei; Xu, Baixue; Tan, Shaoying; Xu, Yufang; Qian, Xuhong; Liang, Xin; Liu, Jianwen

    2016-08-01

    Compared to normal cells, most cancer cells produce ATP by glycolysis under aerobic conditions rather than via the tricarboxylic acid cycle (TCA). This study is intended to determine whether 3B, a novel photosensitizer, can inhibit glycolysis and inflammation in breast cancer cells. We showed that 3B had the ability to repress glucose consumption as well as the generation of ATP, lactate and lactate dehydrogenase. 3B-PDT not only inhibited the expression of IL-1β and IL-6 but also affected the JAK-STAT3 inflammatory pathway in vitro. The present study showed that 3B featured a significant inhibitory effect on the expression of microRNA-155-5p and SOCS1 might serve as a target gene. In vivo studies revealed that 3B inhibited tumor growth and exhibited almost no side effects. Therefore, through the anti-glycolytic effect and breakage of the JAK/STAT3/SOCS1 feedback loop via miR-155-5p, 3B may potentially serve as a potential therapeutic agent against breast cancer.

  1. API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-{kappa}B binding elements: Evidence for a positive feed-back loop pathway resulting in unremitting NF-{kappa}B activation

    SciTech Connect

    Hosokawa, Yoshitaka . E-mail: yhosokaw@aichi-cc.jp; Suzuki, Hiroko; Nakagawa, Masao; Lee, Tae H.; Seto, Masao

    2005-08-19

    t(11;18)(q21;q21) is a characteristic as well as the most frequent chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in a fusion transcript, API2-MALT1. Although API2-MALT1 has been shown to enforce activation of NF-{kappa}B signaling, the transcriptional target genes of this fusion protein remains to be identified. Our analyses of the API2-MALT transfectants suggested that one of the target genes may be the apoptotic inhibitor API2 gene. Luciferase reporter assays with deletion and mutational constructs of the API2 promoter and electrophoretic mobility shift assays established that API2-MALT1 induces transcriptional activation of the API2 gene through two NF-{kappa}B binding elements. Moreover, supershift experiments indicated that these elements are recognized by the NF-{kappa}B p50/p65 heterodimer. Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)-carrying MALT lymphomas, highlighting a positive feedback-loop pathway resulting in unremitting NF-{kappa}B activation.

  2. International Space Station Crew Quarters Ventilation and Acoustic Design Implementation

    NASA Technical Reports Server (NTRS)

    Broyan, James L., Jr.; Cady, Scott M; Welsh, David A.

    2010-01-01

    The International Space Station (ISS) United States Operational Segment has four permanent rack sized ISS Crew Quarters (CQs) providing a private crew member space. The CQs use Node 2 cabin air for ventilation/thermal cooling, as opposed to conditioned ducted air-from the ISS Common Cabin Air Assembly (CCAA) or the ISS fluid cooling loop. Consequently, CQ can only increase the air flow rate to reduce the temperature delta between the cabin and the CQ interior. However, increasing airflow causes increased acoustic noise so efficient airflow distribution is an important design parameter. The CQ utilized a two fan push-pull configuration to ensure fresh air at the crew member's head position and reduce acoustic exposure. The CQ ventilation ducts are conduits to the louder Node 2 cabin aisle way which required significant acoustic mitigation controls. The CQ interior needs to be below noise criteria curve 40 (NC-40). The design implementation of the CQ ventilation system and acoustic mitigation are very inter-related and require consideration of crew comfort balanced with use of interior habitable volume, accommodation of fan failures, and possible crew uses that impact ventilation and acoustic performance. Each CQ required 13% of its total volume and approximately 6% of its total mass to reduce acoustic noise. This paper illustrates the types of model analysis, assumptions, vehicle interactions, and trade-offs required for CQ ventilation and acoustics. Additionally, on-orbit ventilation system performance and initial crew feedback is presented. This approach is applicable to any private enclosed space that the crew will occupy.

  3. 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.

  4. 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.

  5. Visual feedback in stuttering therapy

    NASA Astrophysics Data System (ADS)

    Smolka, Elzbieta

    1997-02-01

    The aim of this paper is to present the results concerning the influence of visual echo and reverberation on the speech process of stutterers. Visual stimuli along with the influence of acoustic and visual-acoustic stimuli have been compared. Following this the methods of implementing visual feedback with the aid of electroluminescent diodes directed by speech signals have been presented. The concept of a computerized visual echo based on the acoustic recognition of Polish syllabic vowels has been also presented. All the research nd trials carried out at our center, aside from cognitive aims, generally aim at the development of new speech correctors to be utilized in stuttering therapy.

  6. International Space Station USOS Crew Quarters Ventilation and Acoustic Design Implementation

    NASA Technical Reports Server (NTRS)

    Broyan, James Lee, Jr.

    2009-01-01

    The International Space Station (ISS) United States Operational Segment (USOS) has four permanent rack sized ISS Crew Quarters (CQ) providing a private crewmember space. The CQ uses Node 2 cabin air for ventilation/thermal cooling, as opposed to conditioned ducted air from the ISS Temperature Humidity Control System or the ISS fluid cooling loop connections. Consequently, CQ can only increase the air flow rate to reduce the temperature delta between the cabin and the CQ interior. However, increasing airflow causes increased acoustic noise so efficient airflow distribution is an important design parameter. The CQ utilized a two fan push-pull configuration to ensure fresh air at the crewmember s head position and reduce acoustic exposure. The CQ interior needs to be below Noise Curve 40 (NC-40). The CQ ventilation ducts are open to the significantly louder Node 2 cabin aisle way which required significantly acoustic mitigation controls. The design implementation of the CQ ventilation system and acoustic mitigation are very inter-related and require consideration of crew comfort balanced with use of interior habitable volume, accommodation of fan failures, and possible crew uses that impact ventilation and acoustic performance. This paper illustrates the types of model analysis, assumptions, vehicle interactions, and trade-offs required for CQ ventilation and acoustics. Additionally, on-orbit ventilation system performance and initial crew feedback is presented. This approach is applicable to any private enclosed space that the crew will occupy.

  7. A Positive Feedback Loop between HEAT SHOCK PROTEIN101 and HEAT STRESS-ASSOCIATED 32-KD PROTEIN Modulates Long-Term Acquired Thermotolerance Illustrating Diverse Heat Stress Responses in Rice Varieties1[W][OPEN

    PubMed Central

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

    2014-01-01

    Heat stress is an important factor that has a negative impact on rice (Oryza sativa) production. To alleviate this problem, it is necessary to extensively understand the genetic basis of heat tolerance and adaptability to heat stress in rice. Here, we report the molecular mechanism underlying heat acclimation memory that confers long-term acquired thermotolerance (LAT) in this monocot plant. Our results showed that a positive feedback loop formed by two heat-inducible genes, HEAT SHOCK PROTEIN101 (HSP101) and HEAT STRESS-ASSOCIATED 32-KD PROTEIN (HSA32), at the posttranscriptional level prolongs the effect of heat acclimation in rice seedlings. The interplay between HSP101 and HSA32 also affects basal thermotolerance of rice seeds. These findings are similar to those reported for the dicot plant Arabidopsis (Arabidopsis thaliana), suggesting a conserved function in plant heat stress response. Comparison between two rice cultivars, japonica Nipponbare and indica N22 showed opposite performance in basal thermotolerance and LAT assays. ‘N22’ seedlings have a higher basal thermotolerance level than cv Nipponbare and vice versa at the LAT level, indicating that these two types of thermotolerance can be decoupled. The HSP101 and HSA32 protein levels were substantially higher in cv Nipponbare than in cv N22 after a long recovery following heat acclimation treatment, at least partly explaining the difference in the LAT phenotype. Our results point out the complexity of thermotolerance diversity in rice cultivars, which may need to be taken into consideration when breeding for heat tolerance for different climate scenarios. PMID:24520156

  8. Cerebral ischemic post-conditioning induces autophagy inhibition and a HMGB1 secretion attenuation feedback loop to protect against ischemia reperfusion injury in an oxygen glucose deprivation cellular model

    PubMed Central

    Wang, Jue; Han, Dong; Sun, Miao; Feng, Juan

    2016-01-01

    Cerebral ischemic postconditioning (IPOC) has been demonstrated to be neuroprotective against cerebral ischemia reperfusion injury. The present study aimed to determine whether IPOC could inhibit autophagy and high mobility group box 1 (HMGB1) release in a PC12 cell oxygen glucose deprivation/reperfusion (OGD/R) model. An 8 h OGD and 24 h reperfusion cellular model was developed to mimic cerebral ischemia reperfusion injury, with 3 cycles of 10 min OGD/5 min reperfusion treatment to imitate IPOC. Cell viability was determined to demonstrate the efficiency of OGD/R, IPOC and autophagy activator, rapamycin (RAP), treatment. Transmission electron microscopy was performed to observe the formation of autophagosomes, and immunofluorescence, western blot and co-immunoprecipitation were used to examine the expression of autophagy-associated proteins and HMGB1. Enzyme-linked immunosorbent assay analysis was conducted to examine the level of HMGB1 in cell supernatants. Additionally, PC12 cells were treated with RAP to examine the effect of autophagy on HMGB1 release, and the effect of recombinant human HMGB1 and Beclin1 small interfering RNA on autophagy was investigated. The present study confirmed that IPOC inhibited autophagy and HMGB1 secretion, autophagy inhibition induced a decrease in HMGB1 secretion, and HMGB1 secretion attenuation caused autophagy inhibition in return, as demonstrated by immunofluorescence and western blot analyses. Autophagy inhibition and HMGB1 secretion attenuation were, therefore, demonstrated to form a feedback loop under IPOC. These mechanisms illustrated the protective effects of IPOC and may accelerate the clinical use of IPOC. PMID:27666823

  9. Cerebral ischemic post‑conditioning induces autophagy inhibition and a HMGB1 secretion attenuation feedback loop to protect against ischemia reperfusion injury in an oxygen glucose deprivation cellular model.

    PubMed

    Wang, Jue; Han, Dong; Sun, Miao; Feng, Juan

    2016-11-01

    Cerebral ischemic postconditioning (IPOC) has been demonstrated to be neuroprotective against cerebral ischemia reperfusion injury. The present study aimed to determine whether IPOC could inhibit autophagy and high mobility group box 1 (HMGB1) release in a PC12 cell oxygen glucose deprivation/reperfusion (OGD/R) model. An 8 h OGD and 24 h reperfusion cellular model was developed to mimic cerebral ischemia reperfusion injury, with 3 cycles of 10 min OGD/5 min reperfusion treatment to imitate IPOC. Cell viability was determined to demonstrate the efficiency of OGD/R, IPOC and autophagy activator, rapamycin (RAP), treatment. Transmission electron microscopy was performed to observe the formation of autophagosomes, and immunofluorescence, western blot and co‑immunoprecipitation were used to examine the expression of autophagy‑associated proteins and HMGB1. Enzyme‑linked immunosorbent assay analysis was conducted to examine the level of HMGB1 in cell supernatants. Additionally, PC12 cells were treated with RAP to examine the effect of autophagy on HMGB1 release, and the effect of recombinant human HMGB1 and Beclin1 small interfering RNA on autophagy was investigated. The present study confirmed that IPOC inhibited autophagy and HMGB1 secretion, autophagy inhibition induced a decrease in HMGB1 secretion, and HMGB1 secretion attenuation caused autophagy inhibition in return, as demonstrated by immunofluorescence and western blot analyses. Autophagy inhibition and HMGB1 secretion attenuation were, therefore, demonstrated to form a feedback loop under IPOC. These mechanisms illustrated the protective effects of IPOC and may accelerate the clinical use of IPOC.

  10. Klystron equalization for RF feedback

    SciTech Connect

    Corredoura, P.

    1993-01-01

    The next generation of colliding beam storage rings support higher luminosities by significantly increasing the number of bunches and decreasing the spacing between respective bunches. The heavy beam loading requires large RF cavity detuning which drives several lower coupled bunch modes very strongly. One technique which has proven to be very successful in reducing the coupled bunch mode driving impedance is RF feedback around the klystron-cavity combination. The gain and bandwidth of the feedback loop is limited by the group delay around the feedback loop. Existing klystrons on the world market have not been optimized for this application and contribute a large portion of the total loop group delay. This paper describes a technique to reduce klystron group delay by adding an equalizing filter to the klystron RF drive. Such a filter was built and tested on a 500 kill klystron as part of the on going PEP-II R&D effort here at SLAC.

  11. Klystron equalization for RF feedback

    SciTech Connect

    Corredoura, P.

    1993-01-01

    The next generation of colliding beam storage rings support higher luminosities by significantly increasing the number of bunches and decreasing the spacing between respective bunches. The heavy beam loading requires large RF cavity detuning which drives several lower coupled bunch modes very strongly. One technique which has proven to be very successful in reducing the coupled bunch mode driving impedance is RF feedback around the klystron-cavity combination. The gain and bandwidth of the feedback loop is limited by the group delay around the feedback loop. Existing klystrons on the world market have not been optimized for this application and contribute a large portion of the total loop group delay. This paper describes a technique to reduce klystron group delay by adding an equalizing filter to the klystron RF drive. Such a filter was built and tested on a 500 kill klystron as part of the on going PEP-II R D effort here at SLAC.

  12. Evaluating Acoustic Emission Signals as an in situ process monitoring technique for Selective Laser Melting (SLM)

    SciTech Connect

    Fisher, Karl A.; Candy, Jim V.; Guss, Gabe; Mathews, M. J.

    2016-10-14

    In situ real-time monitoring of the Selective Laser Melting (SLM) process has significant implications for the AM community. The ability to adjust the SLM process parameters during a build (in real-time) can save time, money and eliminate expensive material waste. Having a feedback loop in the process would allow the system to potentially ‘fix’ problem regions before a next powder layer is added. In this study we have investigated acoustic emission (AE) phenomena generated during the SLM process, and evaluated the results in terms of a single process parameter, of an in situ process monitoring technique.

  13. Relaxation oscillations and hierarchy of feedbacks in MAPK signaling

    PubMed Central

    Kochańczyk, Marek; Kocieniewski, Paweł; Kozłowska, Emilia; Jaruszewicz-Błońska, Joanna; Sparta, Breanne; Pargett, Michael; Albeck, John G.; Hlavacek, William S.; Lipniacki, Tomasz

    2017-01-01

    We formulated a computational model for a MAPK signaling cascade downstream of the EGF receptor to investigate how interlinked positive and negative feedback loops process EGF signals into ERK pulses of constant amplitude but dose-dependent duration and frequency. A positive feedback loop involving RAS and SOS, which leads to bistability and allows for switch-like responses to inputs, is nested within a negative feedback loop that encompasses RAS and RAF, MEK, and ERK that inhibits SOS via phosphorylation. This negative feedback, operating on a longer time scale, changes switch-like behavior into oscillations having a period of 1 hour or longer. Two auxiliary negative feedback loops, from ERK to MEK and RAF, placed downstream of the positive feedback, shape the temporal ERK activity profile but are dispensable for oscillations. Thus, the positive feedback introduces a hierarchy among negative feedback loops, such that the effect of a negative feedback depends on its position with respect to the positive feedback loop. Furthermore, a combination of the fast positive feedback involving slow-diffusing membrane components with slower negative feedbacks involving faster diffusing cytoplasmic components leads to local excitation/global inhibition dynamics, which allows the MAPK cascade to transmit paracrine EGF signals into spatially non-uniform ERK activity pulses. PMID:28045041

  14. Relaxation oscillations and hierarchy of feedbacks in MAPK signaling

    NASA Astrophysics Data System (ADS)

    Kochańczyk, Marek; Kocieniewski, Paweł; Kozłowska, Emilia; Jaruszewicz-Błońska, Joanna; Sparta, Breanne; Pargett, Michael; Albeck, John G.; Hlavacek, William S.; Lipniacki, Tomasz

    2017-01-01

    We formulated a computational model for a MAPK signaling cascade downstream of the EGF receptor to investigate how interlinked positive and negative feedback loops process EGF signals into ERK pulses of constant amplitude but dose-dependent duration and frequency. A positive feedback loop involving RAS and SOS, which leads to bistability and allows for switch-like responses to inputs, is nested within a negative feedback loop that encompasses RAS and RAF, MEK, and ERK that inhibits SOS via phosphorylation. This negative feedback, operating on a longer time scale, changes switch-like behavior into oscillations having a period of 1 hour or longer. Two auxiliary negative feedback loops, from ERK to MEK and RAF, placed downstream of the positive feedback, shape the temporal ERK activity profile but are dispensable for oscillations. Thus, the positive feedback introduces a hierarchy among negative feedback loops, such that the effect of a negative feedback depends on its position with respect to the positive feedback loop. Furthermore, a combination of the fast positive feedback involving slow-diffusing membrane components with slower negative feedbacks involving faster diffusing cytoplasmic components leads to local excitation/global inhibition dynamics, which allows the MAPK cascade to transmit paracrine EGF signals into spatially non-uniform ERK activity pulses.

  15. Acoustic Neuroma

    MedlinePlus

    ... search IRSA's site Unique Hits since January 2003 Acoustic Neuroma Click Here for Acoustic Neuroma Practice Guideline ... to microsurgery. One doctor's story of having an acoustic neuroma In August 1991, Dr. Thomas F. Morgan ...

  16. 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.

  17. Activation of an early feedback survival loop involving phospho-ErbB3 is a general response of melanoma cells to RAF/MEK inhibition and is abrogated by anti-ErbB3 antibodies

    PubMed Central

    2013-01-01

    Background Treatment of advanced melanoma has been improved with the advent of the BRAF inhibitors. However, a limitation to such treatment is the occurrence of resistance. Several mechanisms have been identified to be responsible for the development of resistance, either MEK-dependent or MEK-independent. In order to overcome resistance due to reactivation of MEK signaling, MEK inhibitors are being clinically developed with promising results. However, also in this case resistance inevitably occurs. It has been recently reported that ErbB3, a member of the EGFR receptor family, may be involved in the establishment of drug resistance. Methods Three melanoma cell lines were tested: LOX IMVI (BRAF V600E), MST-L (BRAF V600R) and WM266 (BRAF V600D). Phosphorylation of Receptor Tyrosine Kinases (RTKs) was assessed by an RTK array. Western blot analysis was performed on total protein extracts using anti-ErbB3, anti-AKT and anti-ERK 1/2 antibodies. The expression of neuregulin after vemurafenib treatment was assessed by Real Time PCR and Western blotting. The growth inhibitory effects of vemurafenib, GSK1120212b and/or anti-ErbB3 mAbs were evaluated by in vitro colony formation assays. Results In the present study we demonstrate that ErbB3 is the main RTK undergoing rapidly hyperphosphorylation upon either treatment with a BRAF inhibitor or with a MEK inhibitor in a panel of melanoma cell lines harboring a variety of V600BRAF mutations and that this results in a strong activation of phospho-AKT. Importantly, ErbB3 activation is fully abrogated by the simultaneous use of anti-ErbB3 monoclonal antibodies, which are also shown to potently synergize with BRAF inhibitors in the inactivation of both AKT and ERK pathways and in the inhibition of melanoma cell growth. We show that upregulation of phospho-ErbB3 is due to an autocrine loop involving increased transcription and production of neuregulin by melanoma cells. Conclusions On the basis of these results, we propose that

  18. 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.

  19. 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

  20. 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.

  1. Multi-Point Hermes Acoustic Modem for High-Speed, High-Frequency Acoustic Communications with Low-Frequency Acoustic Control Loop for Real-Time Transmission of AUV-Carried High-Resolution Images and Navigation Data in Support of Ship Hulls Inspection

    DTIC Science & Technology

    2013-08-31

    Message synchronization using the downlink synchronization pulse . ....................... 27 Figure 12: Constellation diagrams for the transmitted and...acoustic downlink, assuming a single reference sequence following the synchronization pulse ...68 Table 12: Signal-to-Noise Ratio per Mission and per Receiver

  2. Investigation of a Parametric Acoustic Receiving Array for Mobile Applications.

    DTIC Science & Technology

    1980-11-05

    KEY WORDS (Continue on reverse side it necessary and identify by block number) PARRAY Turbulence Nonlinear acoustics Phase-locked loop receiver... PARRAY ) exploits the nonlinearity of acoustic waves in water to achieve directional reception of low frequency acoustic waves using only two high...implementation of PARRAYs on submarine platforms. i Analysis, fabrication, and testing of a phase-locked loop receiver ..is described"’’ DDIFORM, 1473

  3. 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.

  4. Aeroelastic structural acoustic control.

    PubMed

    Clark, R L; Frampton, K D

    1999-02-01

    Static, constant-gain, output-feedback control compensators were designed to increase the transmission loss across a panel subjected to mean flow on one surface and a stationary, acoustic half-space on the opposite surface. The multi-input, multi-output control system was based upon the use of an array of colocated transducer pairs. The performance of the static-gain, output-feedback controller was compared to that of the full state-feedback controller using the same control actuator arrays, and was found to yield comparable levels of performance for practical limitations on control effort. Additionally, the resulting static compensators proved to be dissipative in nature, and thus the design varied little as a function of the aeroelastic coupling induced by the fluid-structure interaction under subsonic flow conditions. Several parametric studies were performed, comparing the effects of control-effort penalty as well as the number of transducer pairs used in the control system.

  5. 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

  6. 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.

  7. Acoustic Neuroma

    MedlinePlus

    An acoustic neuroma is a benign tumor that develops on the nerve that connects the ear to the brain. ... can press against the brain, becoming life-threatening. Acoustic neuroma can be difficult to diagnose, because the ...

  8. 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.

  9. 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.

  10. Acoustic Seaglider

    DTIC Science & Technology

    2008-03-07

    a national naval responsibility. Acoustic sensors on mobile, autonomous platforms will enable basic research topics on temporal and spatial...problem and acoustic navigation and communications within the context of distributed autonomous persistent undersea surveillance sensor networks...Acoustic sensors on mobile, autonomous platforms will enable basic research topics on temporal and spatial coherence and the description of ambient

  11. Acoustic seal

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M. (Inventor)

    2006-01-01

    The invention relates to a sealing device having an acoustic resonator. The acoustic resonator is adapted to create acoustic waveforms to generate a sealing pressure barrier blocking fluid flow from a high pressure area to a lower pressure area. The sealing device permits noncontacting sealing operation. The sealing device may include a resonant-macrosonic-synthesis (RMS) resonator.

  12. Acoustic Seal

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M. (Inventor)

    2006-01-01

    The invention relates to a sealing device having an acoustic resonator. The acoustic resonator is adapted to create acoustic waveforms to generate a sealing pressure barrier blocking fluid flow from a high pressure area to a lower pressure area. The sealing device permits noncontacting sealing operation. The sealing device may include a resonant-macrosonic-synthesis (RMS) resonator.

  13. 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.

  14. Recent results in convolution feedback systems.

    NASA Technical Reports Server (NTRS)

    Desoer, C. A.; Callier, F. M.

    1972-01-01

    Survey of recent results obtained by the authors concerning certain types of multiinput, multioutput feedback systems. The discrete-time case as well as the continuous-time case are considered. In each case three theorems are shown. These give insight into the nature of the relationship between the open-loop operator and the closed-loop operator of the system, as well as necessary and sufficient conditions for stability of the closed-loop system when 'unstable' poles are present in their open-loop transfer function.

  15. 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.

  16. Open-loop versus closed-loop control of MEMS devices: choices and issues

    NASA Astrophysics Data System (ADS)

    Borovic, B.; Liu, A. Q.; Popa, D.; Cai, H.; Lewis, F. L.

    2005-10-01

    From a controls point of view, micro electromechanical systems (MEMS) can be driven in an open-loop and closed-loop fashion. Commonly, these devices are driven open-loop by applying simple input signals. If these input signals become more complex by being derived from the system dynamics, we call such control techniques pre-shaped open-loop driving. The ultimate step for improving precision and speed of response is the introduction of feedback, e.g. closed-loop control. Unlike macro mechanical systems, where the implementation of the feedback is relatively simple, in the MEMS case the feedback design is quite problematic, due to the limited availability of sensor data, the presence of sensor dynamics and noise, and the typically fast actuator dynamics. Furthermore, a performance comparison between open-loop and closed-loop control strategies has not been properly explored for MEMS devices. The purpose of this paper is to present experimental results obtained using both open- and closed-loop strategies and to address the comparative issues of driving and control for MEMS devices. An optical MEMS switching device is used for this study. Based on these experimental results, as well as computer simulations, we point out advantages and disadvantages of the different control strategies, address the problems that distinguish MEMS driving systems from their macro counterparts, and discuss criteria to choose a suitable control driving strategy.

  17. LCL Current Control Loop Stability Design

    NASA Astrophysics Data System (ADS)

    Delepaut, Christophe; Kuremyr, Tobias; Martin, Manuel; Tonicello, Ferdinando

    2014-08-01

    Latching Current Limiters include a control loop meant at limiting the current in case of downstream failure. Such current control loop consists typically of a simple proportional feedback gain from a current measurement shunt resistance and may result in very limited phase margin for specified operating conditions. The present paper investigates the combination of a proportional and derivative feedback to mitigate the lack of stability margin, providing a comprehensive overview on designing Latching Current Limiters for stability. For illustration purpose, a LCL based on radiation hardened ITAR free components is considered. A breadboard has been manufactured and the reported phase margin measurements demonstrate performances in line with the analytic results.

  18. Baseband feedback for SAFARI-SPICA using Frequency Domain Multiplexing

    NASA Astrophysics Data System (ADS)

    Bounab, A.; de Korte, P.; Cros, A.; van der Kuur, J.; van Leeuwen, B. J.; Monna, B.; Mossel, R.; Nieuwenhuizen, A.; Ravera, L.

    We report on the performance of the digital baseband feedback circuit developed to readout and process signals from arrays of transition edge sensors for SPICA-SAFARI in frequency domain multiplexing (FDM). The standard procedure to readout the SQUID current amplifiers is to use a feedback loop (flux-locked loop: FLL). However the achievable FFL bandwidth is limited by the cable transport delay t_d, which makes standard feedback inconvenient. A much better approach is to use baseband feedback. We have developed a model of the electronic readout chain for SPICA-SAFARI instrument by using an Anlog-digital co-simulation based on Simulink-System Generator environment.

  19. Feedback traps for virtual potentials

    NASA Astrophysics Data System (ADS)

    Gavrilov, Momčilo; Bechhoefer, John

    2017-03-01

    Feedback traps are tools for trapping and manipulating single charged objects, such as molecules in solution. An alternative to optical tweezers and other single-molecule techniques, they use feedback to counteract the Brownian motion of a molecule of interest. The trap first acquires information about a molecule's position and then applies an electric feedback force to move the molecule. Since electric forces are stronger than optical forces at small scales, feedback traps are the best way to trap single molecules without `touching' them (e.g. by putting them in a small box or attaching them to a tether). Feedback traps can do more than trap molecules: they can also subject a target object to forces that are calculated to be the gradient of a desired potential function U(x). If the feedback loop is fast enough, it creates a virtual potential whose dynamics will be very close to those of a particle in an actual potential U(x). But because the dynamics are entirely a result of the feedback loop-absent the feedback, there is only an object diffusing in a fluid-we are free to specify and then manipulate in time an arbitrary potential U(x,t). Here, we review recent applications of feedback traps to studies on the fundamental connections between information and thermodynamics, a topic where feedback plays an even more fundamental role. We discuss how recursive maximum-likelihood techniques allow continuous calibration, to compensate for drifts in experiments that last for days. We consider ways to estimate work and heat, using them to measure fluctuating energies to a precision of ±0.03 kT over these long experiments. Finally, we compare work and heat measurements of the costs of information erasure, the Landauer limit of kT ln 2 per bit of information erased. We argue that, when you want to know the average heat transferred to a bath in a long protocol, you should measure instead the average work and then infer the heat using the first law of thermodynamics. This

  20. Delayed feedback control of chaos.

    PubMed

    Pyragas, Kestutis

    2006-09-15

    Time-delayed feedback control is well known as a practical method for stabilizing unstable periodic orbits embedded in chaotic attractors. The method is based on applying feedback perturbation proportional to the deviation of the current state of the system from its state one period in the past, so that the control signal vanishes when the stabilization of the target orbit is attained. A brief review on experimental implementations, applications for theoretical models and most important modifications of the method is presented. Recent advancements in the theory, as well as an idea of using an unstable degree of freedom in a feedback loop to avoid a well-known topological limitation of the method, are described in detail.

  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. Musical Acoustics

    NASA Astrophysics Data System (ADS)

    Gough, Colin

    This chapter provides an introduction to the physical and psycho-acoustic principles underlying the production and perception of the sounds of musical instruments. The first section introduces generic aspects of musical acoustics and the perception of musical sounds, followed by separate sections on string, wind and percussion instruments.

  3. 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.

  4. 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.

  5. 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.

  6. Feedback-charging a metallic island

    NASA Astrophysics Data System (ADS)

    Schaller, Gernot

    2017-03-01

    We consider electronic transport through a single-electron quantum dot that is tunnel-coupled to an electronic lead and a metallic island. A background reservoir keeps the metallic island at a thermal state with the ambient temperature, while the charge accumulated on the island is reflected in a time-dependent chemical potential. Without feedback, a current would flow through the system until the chemical potentials of island and lead are equilibrated. A feedback loop can be implemented by a quantum point contact detecting the dot state, classical processing of the result and appropriate feedback actions on the electronic tunneling rates taken, with the objective to direct the current in a preferred direction. Since we directly take the detector counting statistics into account, this automatically includes measurement errors in the description. When mainly the rates are modified but hardly any energy is exchanged with the system, this feedback loop effectively implements a Maxwell demon, capable of transporting electrons against an electric bias and thereby charging the metallic island. Once the feedback protocol is stopped, the metallic island simply discharges. We find that a quantitative detector model may be useful for a realistic statistical description of feedback loops.

  7. Closed-Loop Control for Sonic Fatigue Testing Systems

    NASA Technical Reports Server (NTRS)

    Rizzi, Stephen A.; Bossaert, Guido

    2001-01-01

    This article documents recent improvements to the acoustic control system of the Thermal Acoustic Fatigue Apparatus (TAFA), a progressive wave tube test facility at the NASA Langley Research Center, Hampton, VA. A brief summary of past acoustic performance is first given to serve as a basis of comparison with the new performance data using a multiple-input, closed-loop, narrow-band controller. Performance data in the form of test section acoustic power spectral densities and coherence are presented for a variety of input spectra including uniform, band-limited random and an expendable launch vehicle payload bay environment.

  8. A Very High Bit Rate Broadband Acoustic Modem for Short-to-Medium Range Data Transmission in Ports And Shallow Water Using Spread Spectrum Modulation and Decision Feedback Equalizing

    DTIC Science & Technology

    2008-09-30

    using the high-resolution, low-noise acquisition system developed by EdgeTech in collaboration with FAU . The acquisition system produces complex base...direct transducer coupling; (2) System calibration in the acoustic tank at FAU SeaTech; (3) Field tests in the FAU SeaTech marina. During the later...the FAU SeaTech marina on July 25th, 2008 (Figure 3). During the SeaTech demonstration, the source was operating at 32 W of output acoustic power

  9. 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.

  10. Haptic gas pedal feedback.

    PubMed

    Mulder, M; Mulder, M; van Paassen, M M; Abbink, D A

    2008-11-01

    Active driver support systems either automate a control task or present warnings to drivers when their safety is seriously degraded. In a novel approach, utilising neither automation nor discrete warnings, a haptic gas pedal (accelerator) interface was developed that continuously presents car-following support information, keeping the driver in the loop. This interface was tested in a fixed-base driving simulator. Twenty-one drivers between the ages of 24 and 30 years participated in a driving experiment to investigate the effects of haptic gas pedal feedback on car-following behaviour. Results of the experiment indicate that when haptic feedback was presented to the drivers, some improvement in car-following performance was achieved, while control activity decreased. Further research is needed to investigate the effectiveness of the system in more varied driving conditions. Haptics is an under-used modality in the application of human support interfaces, which usually draw on vision or hearing. This study demonstrates how haptics can be used to create an effective driver support interface.

  11. The Dynamics of the Stapedial Acoustic Reflex.

    NASA Astrophysics Data System (ADS)

    Moss, Sherrin Mary

    Available from UMI in association with The British Library. This thesis aims to separate the neural and muscular components of the stapedial acoustic reflex, both anatomically and physiologically. It aims to present an hypothesis to account for the differences between ipsilateral and contralateral reflex characteristics which have so far been unexplained, and achieve a greater understanding of the mechanisms underlying the reflex dynamics. A technique enabling faithful reproduction of the time course of the reflex is used throughout the experimental work. The technique measures tympanic membrane displacement as a result of reflex stapedius muscle contraction. The recorded response can be directly related to the mechanics of the middle ear and stapedius muscle contraction. Some development of the technique is undertaken by the author. A model of the reflex neural arc and stapedius muscle dynamics is evolved that is based upon a second order system. The model is unique in that it includes a latency in the ipsilateral negative feedback loop. Oscillations commonly observed on reflex responses are seen to be produced because of the inclusion of a latency in the feedback loop. The model demonstrates and explains the complex relationships between neural and muscle dynamic parameters observed in the experimental work. This more comprehensive understanding of the interaction between the stapedius dynamics and the neural arc of the reflex would not usually have been possible using human subjects, coupled with a non-invasive measurement technique. Evidence from the experimental work revealed the ipsilateral reflex to have, on average, a 5 dB lower threshold than the contralateral reflex. The oscillatory charcteristics, and the steady state response, of the contralateral reflex are also seen to be significantly different from those of the ipsilateral reflex. An hypothesis to account for the experimental observations is proposed. It is propounded that chemical neurotransmitters

  12. Room Acoustics

    NASA Astrophysics Data System (ADS)

    Kuttruff, Heinrich; Mommertz, Eckard

    The traditional task of room acoustics is to create or formulate conditions which ensure the best possible propagation of sound in a room from a sound source to a listener. Thus, objects of room acoustics are in particular assembly halls of all kinds, such as auditoria and lecture halls, conference rooms, theaters, concert halls or churches. Already at this point, it has to be pointed out that these conditions essentially depend on the question if speech or music should be transmitted; in the first case, the criterion for transmission quality is good speech intelligibility, in the other case, however, the success of room-acoustical efforts depends on other factors that cannot be quantified that easily, not least it also depends on the hearing habits of the listeners. In any case, absolutely "good acoustics" of a room do not exist.

  13. Water Stream "Loop-the-Loop"

    ERIC Educational Resources Information Center

    Jefimenko, Oleg

    1974-01-01

    Discusses the design of a modified loop-the-loop apparatus in which a water stream is used to illustrate centripetal forces and phenomena of high-velocity hydrodynamics. Included are some procedures of carrying out lecture demonstrations. (CC)

  14. 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.

  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. Robustness with observers. [linear optimal feedback control systems

    NASA Technical Reports Server (NTRS)

    Doyle, J. C.; Stein, G.

    1979-01-01

    The paper describes an adjustment procedure for observer-based linear control systems which asymptotically achieves the same loop transfer functions (and hence the same relative stability, robustness, and disturbance rejection properties) as full-state feedback control implementations. Full-state loop-transfer properties can be recovered asymptotically if the plant is minimum phase; this occurs at the expense of noise performance.

  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. Exponential passivity for output feedback stabilisation of nonlinear uncertain systems

    NASA Astrophysics Data System (ADS)

    Benabdallah, Amel

    2010-11-01

    In this article, we address the problem of stabilisation by output feedback for a class of uncertain systems. We consider uncertain systems with a nominal part which is affine in the control and an uncertain part which is norm bounded by a known function. We propose an output feedback such that the closed loop system is globally exponentially stable.

  19. Tactile feedback improves auditory spatial localization.

    PubMed

    Gori, Monica; Vercillo, Tiziana; Sandini, Giulio; Burr, David

    2014-01-01

    Our recent studies suggest that congenitally blind adults have severely impaired thresholds in an auditory spatial bisection task, pointing to the importance of vision in constructing complex auditory spatial maps (Gori et al., 2014). To explore strategies that may improve the auditory spatial sense in visually impaired people, we investigated the impact of tactile feedback on spatial auditory localization in 48 blindfolded sighted subjects. We measured auditory spatial bisection thresholds before and after training, either with tactile feedback, verbal feedback, or no feedback. Audio thresholds were first measured with a spatial bisection task: subjects judged whether the second sound of a three sound sequence was spatially closer to the first or the third sound. The tactile feedback group underwent two audio-tactile feedback sessions of 100 trials, where each auditory trial was followed by the same spatial sequence played on the subject's forearm; auditory spatial bisection thresholds were evaluated after each session. In the verbal feedback condition, the positions of the sounds were verbally reported to the subject after each feedback trial. The no feedback group did the same sequence of trials, with no feedback. Performance improved significantly only after audio-tactile feedback. The results suggest that direct tactile feedback interacts with the auditory spatial localization system, possibly by a process of cross-sensory recalibration. Control tests with the subject rotated suggested that this effect occurs only when the tactile and acoustic sequences are spatially congruent. Our results suggest that the tactile system can be used to recalibrate the auditory sense of space. These results encourage the possibility of designing rehabilitation programs to help blind persons establish a robust auditory sense of space, through training with the tactile modality.

  20. 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

  1. Feedback linearization of power amplifiers for digital microwave communications

    NASA Astrophysics Data System (ADS)

    Weaver, C. F.; Taylor, D. P.

    A new method of linearizing high capacity microwave radio power amplifiers (PA) is presented. This method which is mainly applicable to GaAs FET PA's, uses feedback around a linear quadrature amplitude modulation (QAM) modulator, a PA, and a linear coherent QAM demodulator. A simulation model is given and simulations are presented to demonstrate the improvement over unlinearized PA's. Loop stability is discussed and the peak eye closure performance versus PA input power, loop gain, and loop bandwidth are presented.

  2. Cavitation controlled acoustic probe for fabric spot cleaning and moisture monitoring

    DOEpatents

    Sheen, Shuh-Haw; Chien, Hual-Te; Raptis, Apostolos C.

    1997-01-01

    A method and apparatus are provided for monitoring a fabric. An acoustic probe generates acoustic waves relative to the fabric. An acoustic sensor, such as an accelerometer is coupled to the acoustic probe for generating a signal representative of cavitation activity in the fabric. The generated cavitation activity representative signal is processed to indicate moisture content of the fabric. A feature of the invention is a feedback control signal is generated responsive to the generated cavitation activity representative signal. The feedback control signal can be used to control the energy level of the generated acoustic waves and to control the application of a cleaning solution to the fabric.

  3. Feedback linearization for control of air breathing engines

    NASA Technical Reports Server (NTRS)

    Phillips, Stephen; Mattern, Duane

    1991-01-01

    The method of feedback linearization for control of the nonlinear nozzle and compressor components of an air breathing engine is presented. This method overcomes the need for a large number of scheduling variables and operating points to accurately model highly nonlinear plants. Feedback linearization also results in linear closed loop system performance simplifying subsequent control design. Feedback linearization is used for the nonlinear partial engine model and performance is verified through simulation.

  4. Air Force research in human sensory feedback for telepresence

    NASA Technical Reports Server (NTRS)

    Julian, Ronald G.

    1993-01-01

    Telepresence operations require high quality information transfer between the human master and the remotely located slave. Present Air Force research focuses on the human aspects of the information needed to complete the control/feedback loop. Work in three key areas of human sensory feedback for manipulation of objects are described. Specific projects in each key area are outlined, including research tools (hardware), planned research, and test results. Nonmanipulative feedback technologies are mentioned to complete the advanced teleoperation discussions.

  5. Time-Delayed Quantum Feedback Control.

    PubMed

    Grimsmo, Arne L

    2015-08-07

    A theory of time-delayed coherent quantum feedback is developed. More specifically, we consider a quantum system coupled to a bosonic reservoir creating a unidirectional feedback loop. It is shown that the dynamics can be mapped onto a fictitious series of cascaded quantum systems, where the system is driven by past versions of itself. The derivation of this model relies on a tensor network representation of the system-reservoir time propagator. For concreteness, this general theory is applied to a driven two-level atom scattering into a coherent feedback loop. We demonstrate how delay effects can qualitatively change the dynamics of the atom and how quantum control can be implemented in the presence of time delays.

  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. Acoustic biosensors

    PubMed Central

    Fogel, Ronen; Seshia, Ashwin A.

    2016-01-01

    Resonant and acoustic wave devices have been researched for several decades for application in the gravimetric sensing of a variety of biological and chemical analytes. These devices operate by coupling the measurand (e.g. analyte adsorption) as a modulation in the physical properties of the acoustic wave (e.g. resonant frequency, acoustic velocity, dissipation) that can then be correlated with the amount of adsorbed analyte. These devices can also be miniaturized with advantages in terms of cost, size and scalability, as well as potential additional features including integration with microfluidics and electronics, scaled sensitivities associated with smaller dimensions and higher operational frequencies, the ability to multiplex detection across arrays of hundreds of devices embedded in a single chip, increased throughput and the ability to interrogate a wider range of modes including within the same device. Additionally, device fabrication is often compatible with semiconductor volume batch manufacturing techniques enabling cost scalability and a high degree of precision and reproducibility in the manufacturing process. Integration with microfluidics handling also enables suitable sample pre-processing/separation/purification/amplification steps that could improve selectivity and the overall signal-to-noise ratio. Three device types are reviewed here: (i) bulk acoustic wave sensors, (ii) surface acoustic wave sensors, and (iii) micro/nano-electromechanical system (MEMS/NEMS) sensors. PMID:27365040

  8. Acoustic biosensors.

    PubMed

    Fogel, Ronen; Limson, Janice; Seshia, Ashwin A

    2016-06-30

    Resonant and acoustic wave devices have been researched for several decades for application in the gravimetric sensing of a variety of biological and chemical analytes. These devices operate by coupling the measurand (e.g. analyte adsorption) as a modulation in the physical properties of the acoustic wave (e.g. resonant frequency, acoustic velocity, dissipation) that can then be correlated with the amount of adsorbed analyte. These devices can also be miniaturized with advantages in terms of cost, size and scalability, as well as potential additional features including integration with microfluidics and electronics, scaled sensitivities associated with smaller dimensions and higher operational frequencies, the ability to multiplex detection across arrays of hundreds of devices embedded in a single chip, increased throughput and the ability to interrogate a wider range of modes including within the same device. Additionally, device fabrication is often compatible with semiconductor volume batch manufacturing techniques enabling cost scalability and a high degree of precision and reproducibility in the manufacturing process. Integration with microfluidics handling also enables suitable sample pre-processing/separation/purification/amplification steps that could improve selectivity and the overall signal-to-noise ratio. Three device types are reviewed here: (i) bulk acoustic wave sensors, (ii) surface acoustic wave sensors, and (iii) micro/nano-electromechanical system (MEMS/NEMS) sensors.

  9. 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.

  10. 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.

  11. 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

  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 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

  13. Feedback: Breakfast of Champions.

    ERIC Educational Resources Information Center

    Justman, Jeffrey J.

    Feedback is an important skill that people need to learn in life. Feedback is crucial in a public speaking class to improve speaking skills. Providing and receiving feedback is what champions feed on to be successful, thus feedback is called the "Breakfast of Champions." Feedback builds speakers' confidence. Providing in-depth feedback…

  14. Constant-Frequency Pulsed Phase-Locked-Loop Measuring Device

    NASA Technical Reports Server (NTRS)

    Yost, William T.; Cantrell, John H.; Kushnick, Peter W.

    1992-01-01

    Constant-frequency pulsed phase-locked-loop measuring device is sensitive to small changes in phase velocity and easily automated. Based on use of fixed-frequency oscillator in measuring small changes in ultrasonic phase velocity when sample exposed to such changes in environment as changes in pressure and temperature. Automatically balances electrical phase shifts against acoustical phase shifts to obtain accurate measurements of acoustical phase shifts.

  15. 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.

  16. 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.

  17. 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.

  18. Tuneable vibration absorber using acceleration and displacement feedback

    NASA Astrophysics Data System (ADS)

    Alujević, N.; Tomac, I.; Gardonio, P.

    2012-06-01

    This study is concerned with the analysis and design of a tuneable vibration absorber, which is composed by a flexible beam with a clamping block in the middle and two masses symmetrically mounted at the two ends. The free length of the beam is used to accommodate piezoelectric strain actuators. The two masses at the ends are equipped with inertial accelerometers. This arrangement is used to generate two independent acceleration feedback control loops that produce virtual mass effects, which shift the absorbing frequency of the device. Another arrangement is also studied where the two accelerometer outputs are time-integrated twice in order to implement displacement feedback loops that change the beam stiffness to shift the characteristic frequency of the device. The two feedback approaches are first analysed theoretically, using a mobility-impedance model, and then experimentally on a prototype absorber unit. The stability of the feedback loops is studied using the Nyquist criterion in order to estimate the limits on the tuneable range of frequencies which are set by the maximum stable feedback gains. The study indicates that the stability margins for the acceleration feedback loops substantially depend on the application of an appropriate low-pass filter. On the contrary, the implementation of displacement feedback gives better stability margins.

  19. 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.

  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.

  1. On the control of linear systems using two level periodic output feedback.

    NASA Technical Reports Server (NTRS)

    Welch, R. V.; Levine, W. S.

    1972-01-01

    A class of second order linear time-invariant systems which are unstable for any constant feedback but which are stabilized by a two level periodic feedback is identified. Necessary and sufficient conditions for this type of stabilization are found. In addition, the sensitivity of the closed-loop system to changes in feedback gains is investigated.

  2. A frequency-selective feedback model of auditory efferent suppression and its implications for the recognition of speech in noise.

    PubMed

    Clark, Nicholas R; Brown, Guy J; Jürgens, Tim; Meddis, Ray

    2012-09-01

    The potential contribution of the peripheral auditory efferent system to our understanding of speech in a background of competing noise was studied using a computer model of the auditory periphery and assessed using an automatic speech recognition system. A previous study had shown that a fixed efferent attenuation applied to all channels of a multi-channel model could improve the recognition of connected digit triplets in noise [G. J. Brown, R. T. Ferry, and R. Meddis, J. Acoust. Soc. Am. 127, 943-954 (2010)]. In the current study an anatomically justified feedback loop was used to automatically regulate separate attenuation values for each auditory channel. This arrangement resulted in a further enhancement of speech recognition over fixed-attenuation conditions. Comparisons between multi-talker babble and pink noise interference conditions suggest that the benefit originates from the model's ability to modify the amount of suppression in each channel separately according to the spectral shape of the interfering sounds.

  3. Acoustic-velocity measurements in materials using a regenerative method

    DOEpatents

    Laine, E.F.

    1982-09-30

    Acoustic energy is propatated through earth material between an electro-acoustic generator and a receiver which converts the received acoustic energy into electrical signals. A closed loop is formed by a variable gain amplifier system connected between the receiver and the generator. The gain of the amplifier system is increased until sustained oscillations are produced in the closed loop. The frequency of the oscillations is measured as an indication of the acoustic propagation velocity through the earth material. The amplifier gain is measured as an indication of the acoustic attenuation through the earth materials. The method is also applicable to the non-destructive testing of structural materials, such as steel, aluminum and concrete.

  4. Acoustic velocity measurements in materials using a regenerative method

    DOEpatents

    Laine, Edwin F.

    1986-01-01

    Acoustic energy is propagated through earth material between an electro-acoustic generator and a receiver which converts the received acoustic energy into electrical signals. A closed loop is formed by a variable gain amplifier system connected between the receiver and the generator. The gain of the amplifier system is increased until sustained oscillations are produced in the closed loop. The frequency of the oscillations is measured as an indication of the acoustic propagation velocity through the earth material. The amplifier gain is measured as an indication of the acoustic attenuation through the earth materials. The method is also applicable to the non-destructive testing of structural materials, such as steel, aluminum and concrete.

  5. Nonlinear Acoustics

    DTIC Science & Technology

    1974-02-14

    Wester- velt. [60] Streaming. In 1831, Michael Faraday [61] noted that currents of air were set up in the neighborhood of vibrating plates-the first... ducei in the case of a paramettc amy (from Berktay an Leahy 141). C’ "". k•, SEC 10.1 NONLINEAR ACOUSTICS 345 The principal results of their analysis

  6. Systems approach to identification of feedback enhanced optical tweezers

    NASA Astrophysics Data System (ADS)

    Sehgal, Hullas; Aggarwal, Tanuj; Salapaka, Murti V.

    2008-08-01

    Feedback enhanced optical tweezers, based on Proportional and Integral (PI) control, are routinely used for increasing the stiffness of optical traps. Digital implementation of PI controller, using DSP or FPGA, enables easy maneuverability of feedback gains. In this paper, we report occurrence of a peak in the thermal noise power spectrum of the trapped bead as the proportional gain is cranked up, which imposes a limit on how stiff a trap can be made using position feedback. We explain the reasons for the deviant behavior in the power spectrum and present a mathematical formula to account for the anomaly, which is in very good agreement with the experimental observations. Further, we present a new method to do the closed loop system identification of feedback enhanced optical tweezers by applying a frequency chirp. The system model thus obtained greatly predicts the closed loop behavior of our feedback based optical tweezers system.

  7. Opto-acoustic thrombolysis

    DOEpatents

    Celliers, Peter; Da Silva, Luiz; Glinsky, Michael; London, Richard; Maitland, Duncan; Matthews, Dennis; Fitch, Pat

    2000-01-01

    This invention is a catheter-based device for generating an ultrasound excitation in biological tissue. Pulsed laser light is guided through an optical fiber to provide the energy for producing the acoustic vibrations. The optical energy is deposited in a water-based absorbing fluid, e.g. saline, thrombolytic agent, blood or thrombus, and generates an acoustic impulse in the fluid through thermoelastic and/or thermodynamic mechanisms. By pulsing the laser at a repetition rate (which may vary from 10 Hz to 100 kHz) an ultrasonic radiation field can be established locally in the medium. This method of producing ultrasonic vibrations can be used in vivo for the treatment of stroke-related conditions in humans, particularly for dissolving thrombus or treating vasospasm. The catheter can also incorporate thrombolytic drug treatments as an adjunct therapy and it can be operated in conjunction with ultrasonic detection equipment for imaging and feedback control and with optical sensors for characterization of thrombus type and consistency.

  8. Acoustic transducer for acoustic microscopy

    DOEpatents

    Khuri-Yakub, Butrus T.; Chou, Ching H.

    1990-01-01

    A shear acoustic transducer-lens system in which a shear polarized piezoelectric material excites shear polarized waves at one end of a buffer rod having a lens at the other end which excites longitudinal waves in a coupling medium by mode conversion at selected locations on the lens.

  9. Acoustic transducer for acoustic microscopy

    DOEpatents

    Khuri-Yakub, B.T.; Chou, C.H.

    1990-03-20

    A shear acoustic transducer-lens system is described in which a shear polarized piezoelectric material excites shear polarized waves at one end of a buffer rod having a lens at the other end which excites longitudinal waves in a coupling medium by mode conversion at selected locations on the lens. 9 figs.

  10. 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.

  11. MRI-guided therapeutic ultrasound: Temperature feedback control for extracorporeal and endoluminal applicators

    NASA Astrophysics Data System (ADS)

    Salomir, Rares

    2005-09-01

    Therapeutic ultrasound is a mini-invasive and promising tool for in situ ablation of non-resectable tumors in uterus, breast, esophagus, kidney, liver, etc. Extracorporeal, endoluminal, and interstitial applicators have been successfully tested to date. Magnetic resonance imaging (MRI) is the only available technique providing non-invasive temperature mapping, together with excellent contrast of soft tissue. Coupling of these two technologies offers the advantage of both: (1) on line spatial guidance to the target region, and (2) thermal dose control during the treatment. This talk will provide an overview of the author's experience with automatic, active feedback control of the temperature evolution in tissues, which has been demonstrated with MRI compatible extracorporeal transducers (focused beam) or endoluminal applicators (plane waves). The feedback loop is based on fast switching capabilities of the driving electronics and real time data transfer out of the MR scanner. Precision of temperature control was typically better than 1°C. This approach is expected to improve the efficacy of the treatment (complete tumor ablation) and the thermal security of the critical regions crossed by the acoustic beam. It also permits one to reach an under-lethal heating regime for local drug delivery using thermosensitive liposomes or gene expression control based on hsp promoters.

  12. 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…

  13. Acoustic chaos

    SciTech Connect

    Lauterborn, W.; Parlitz, U.; Holzfuss, J.; Billo, A.; Akhatov, I.

    1996-06-01

    Acoustic cavitation, a complex, spatio-temporal dynamical system, is investigated with respect to its chaotic properties. The sound output, the {open_quote}{open_quote}noise{close_quote}{close_quote}, is subjected to time series analysis. The spatial dynamics of the bubble filaments is captured by high speed holographic cinematography and subsequent digital picture processing from the holograms. Theoretical models are put forward for describing the pattern formation. {copyright} {ital 1996 American Institute of Physics.}

  14. Medical Acoustics

    NASA Astrophysics Data System (ADS)

    Beach, Kirk W.; Dunmire, Barbrina

    Medical acoustics can be subdivided into diagnostics and therapy. Diagnostics are further separated into auditory and ultrasonic methods, and both employ low amplitudes. Therapy (excluding medical advice) uses ultrasound for heating, cooking, permeablizing, activating and fracturing tissues and structures within the body, usually at much higher amplitudes than in diagnostics. Because ultrasound is a wave, linear wave physics are generally applicable, but recently nonlinear effects have become more important, even in low-intensity diagnostic applications.

  15. Acoustic dose and acoustic dose-rate.

    PubMed

    Duck, Francis

    2009-10-01

    Acoustic dose is defined as the energy deposited by absorption of an acoustic wave per unit mass of the medium supporting the wave. Expressions for acoustic dose and acoustic dose-rate are given for plane-wave conditions, including temporal and frequency dependencies of energy deposition. The relationship between the acoustic dose-rate and the resulting temperature increase is explored, as is the relationship between acoustic dose-rate and radiation force. Energy transfer from the wave to the medium by means of acoustic cavitation is considered, and an approach is proposed in principle that could allow cavitation to be included within the proposed definitions of acoustic dose and acoustic dose-rate.

  16. Pseudonoise code tracking loop

    NASA Technical Reports Server (NTRS)

    Laflame, D. T. (Inventor)

    1980-01-01

    A delay-locked loop is presented for tracking a pseudonoise (PN) reference code in an incoming communication signal. The loop is less sensitive to gain imbalances, which can otherwise introduce timing errors in the PN reference code formed by the loop.

  17. Disturbance-free phase-shifting laser diode interferometer using adaptive feedback control

    SciTech Connect

    Suzuki, Takamasa; Takahashi, Tsutomu; Sasaki, Osami

    2009-10-10

    A feedback-control-equipped phase-shifting laser diode interferometer that eliminates external disturbance is proposed. The feedback loop is stabilized by adaptive control of the polarity of the interference signal. Conventional phase-shifting interferometry can be used with the feedback control, resulting in simplified signal processing and accurate measurement. Several experiments confirm the stability of the feedback control with a measurement repeatability of 1.8 nm.

  18. Virtual acoustics for music practice rooms

    NASA Astrophysics Data System (ADS)

    Freiheit, Ron

    2003-04-01

    The use of virtual acoustics has provided a new level of practice experience for the musician. By integrating the sound isolation of music practice rooms with the signal processing of an active acoustic system (with time variant-gain before feedback) musicians can now benefit from the experience of practicing in multiple acoustic environments. Musicians select from various acoustics environments from a typical small practice room to that of a large space such as a sports arena. The variability of the acoustic environment allows the musician to hear clearly their intonation and articulation, which may be difficult to discern in a small practice room. To effectively communicate the various acoustics environments, the musicians must be immersed in the sound field of the active acoustics without being able to discern source locations of the speakers. The system must also be able to support the dynamic range of the musicians without presenting artifacts of its own such as system noise or audible distortion. This paper deals with the design constraints needed to meet these requirements as well the antidotal responses from musicians who have used these environments for practice.

  19. 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

  20. Acoustic Tooth Cleaner

    NASA Technical Reports Server (NTRS)

    Heyman, J. S.

    1984-01-01

    Acoustically-energized water jet aids in plaque breakdown. Acoustic Wand includes acoustic transducer 1/4 wave plate, and tapered cone. Together elements energize solution of water containing mild abrasive injected into mouth to help prevent calculous buildup.

  1. 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.

  2. Piezoceramic Actuator Placement for Acoustic Control of Panels

    NASA Technical Reports Server (NTRS)

    Bevan, Jeffrey S.

    2000-01-01

    Optimum placement of multiple traditional piezoceramic actuators is determined for active structural acoustic control of flat panels. The structural acoustic response is determined using acoustic radiation filters and structural surface vibration characteristics. Linear Quadratic Regulator (LQR) control is utilized to determine the optimum state feedback gain for active structural acoustic control. The optimum actuator location is determined by minimizing the structural acoustic radiated noise using a modified genetic algorithm. Experimental tests are conducted and compared to analytical results. Anisotropic piezoceramic actuators exhibit enhanced performance when compared to traditional isotropic piezoceramic actuators. As a result of the inherent isotropy, these advanced actuators develop strain along the principal material axis. The orientation of anisotropic actuators is investigated on the effect of structural vibration and acoustic control of curved and flat panels. A fully coupled shallow shell finite element formulation is developed to include anisotropic piezoceramic actuators for shell structures.

  3. Air-coupled acoustic thermography for in-situ evaluation

    NASA Technical Reports Server (NTRS)

    Zalameda, Joseph N. (Inventor); Winfree, William P. (Inventor); Yost, William T. (Inventor)

    2010-01-01

    Acoustic thermography uses a housing configured for thermal, acoustic and infrared radiation shielding. For in-situ applications, the housing has an open side adapted to be sealingly coupled to a surface region of a structure such that an enclosed chamber filled with air is defined. One or more acoustic sources are positioned to direct acoustic waves through the air in the enclosed chamber and towards the surface region. To activate and control each acoustic source, a pulsed signal is applied thereto. An infrared imager focused on the surface region detects a thermal image of the surface region. A data capture device records the thermal image in synchronicity with each pulse of the pulsed signal such that a time series of thermal images is generated. For enhanced sensitivity and/or repeatability, sound and/or vibrations at the surface region can be used in feedback control of the pulsed signal applied to the acoustic sources.

  4. Piezoceramic Actuator Placement for Acoustic Control of Panels

    NASA Technical Reports Server (NTRS)

    Bevan, Jeffrey S.; Turner, Travis L. (Technical Monitor)

    2001-01-01

    Optimum placement of multiple traditional piezoceramic actuators is determined for active structural acoustic control of flat panels. The structural acoustic response is determined using acoustic radiation filters and structural surface vibration characteristics. Linear Quadratic Regulator (LQR) control is utilized to determine the optimum state feedback gain for active structural acoustic control. The optimum actuator location is determined by minimizing the structural acoustic radiated noise using a modified genetic algorithm. Experimental tests are conducted and compared to analytical results. Anisotropic piezoceramic actuators exhibits enhanced performance when compared to traditional isotropic piezoceramic actuators. As a result of the inherent isotropy, these advanced actuators develop strain along the principal material axis. The orientation of anisotropic actuators is investigated on the effect of structural vibration and acoustic control of curved and flat panels. A fully coupled shallow shell finite element formulation is developed to include anisotropic piezoceramic actuators for shell structures.

  5. Feedback control of bimodal wake dynamics

    NASA Astrophysics Data System (ADS)

    Li, Ruiying; Barros, Diogo; Borée, Jacques; Cadot, Olivier; Noack, Bernd R.; Cordier, Laurent

    2016-10-01

    Feedback control is applied to symmetrize the bimodal dynamics of a turbulent blunt body wake. The flow is actuated with two lateral slit jets and monitored with pressure sensors at the rear surface. The physics-based controller is inferred from preliminary open-loop tests and is capable of symmetrizing the wake. A slight pressure recovery is achieved due to the net balance between the favourable effect of wake symmetrization and adverse effect of shear-layer mixing and vortex shedding amplification.

  6. The PTTG1-targeting miRNAs miR-329, miR-300, miR-381, and miR-655 inhibit pituitary tumor cell tumorigenesis and are involved in a p53/PTTG1 regulation feedback loop.

    PubMed

    Liang, Hai-qian; Wang, Ren-jie; Diao, Cai-feng; Li, Jian-wei; Su, Jing-liang; Zhang, Sai

    2015-10-06

    Deregulation of the pituitary tumor transforming gene (PTTG1), a newly discovered oncogene, is a hallmark of various malignancies, including pituitary tumors. However, the mechanisms regulating PTTG1 expression are still needed to be explored. MicroRNAs (miRNAs) are a novel class of small RNA molecules that act as posttranscriptional regulators of gene expression and can play a significant role in tumor development. Here, we identified a series of miRNAs, namely, miR-329, miR-300, miR-381 and miR-655, which could target PTTG1 messenger RNA and inhibit its expression. Interestingly, all four miRNAs significantly that are downregulated in pituitary tumors were mapped to the 14q32.31 locus, which acts as a tumor suppressor in several cancers. Functional studies show that the PTTG1-targeting miRNAs inhibit proliferation, migration and invasion but induce apoptosis in GH3 and MMQ cells. Furthermore, overexpression of a PTTG1 expression vector lacking the 3'UTR partially reverses the tumor suppressive effects of these miRNAs. Next, we identified the promoter region of PTTG1-targeting miRNAs with binding sites for p53. In our hands, p53 transcriptionally activated the expression of these miRNAs in pituitary tumor cells. Finally, we found that PTTG1 could inhibit p53 transcriptional activity to the four miRNAs. These data indicate the existence of a feedback loop between PTTG1 targeting miRNAs, PTTG1 and p53 that promotes pituitary tumorigenesis. Together, these findings suggest that these PTTG1-targeting miRNAs are important players in the regulation of pituitary tumorigenesis and that these miRNAs may serve as valuable therapeutic targets for cancer treatment.

  7. The PTTG1-targeting miRNAs miR-329, miR-300, miR-381, and miR-655 inhibit pituitary tumor cell tumorigenesis and are involved in a p53/PTTG1 regulation feedback loop

    PubMed Central

    Diao, Cai-feng; Li, Jian-wei; Su, Jing-liang; Zhang, Sai

    2015-01-01

    Deregulation of the pituitary tumor transforming gene (PTTG1), a newly discovered oncogene, is a hallmark of various malignancies, including pituitary tumors. However, the mechanisms regulating PTTG1 expression are still needed to be explored. MicroRNAs (miRNAs) are a novel class of small RNA molecules that act as posttranscriptional regulators of gene expression and can play a significant role in tumor development. Here, we identified a series of miRNAs, namely, miR-329, miR-300, miR-381 and miR-655, which could target PTTG1 messenger RNA and inhibit its expression. Interestingly, all four miRNAs significantly that are downregulated in pituitary tumors were mapped to the 14q32.31 locus, which acts as a tumor suppressor in several cancers. Functional studies show that the PTTG1-targeting miRNAs inhibit proliferation, migration and invasion but induce apoptosis in GH3 and MMQ cells. Furthermore, overexpression of a PTTG1 expression vector lacking the 3′UTR partially reverses the tumor suppressive effects of these miRNAs. Next, we identified the promoter region of PTTG1-targeting miRNAs with binding sites for p53. In our hands, p53 transcriptionally activated the expression of these miRNAs in pituitary tumor cells. Finally, we found that PTTG1 could inhibit p53 transcriptional activity to the four miRNAs. These data indicate the existence of a feedback loop between PTTG1 targeting miRNAs, PTTG1 and p53 that promotes pituitary tumorigenesis. Together, these findings suggest that these PTTG1-targeting miRNAs are important players in the regulation of pituitary tumorigenesis and that these miRNAs may serve as valuable therapeutic targets for cancer treatment. PMID:26320179

  8. Feedbacks in human-landscape systems

    NASA Astrophysics Data System (ADS)

    Chin, Anne

    2015-04-01

    As human interactions with Earth systems intensify in the "Anthropocene", understanding the complex relationships among human activity, landscape change, and societal responses to those changes is increasingly important. Interdisciplinary research centered on the theme of "feedbacks" in human-landscape systems serves as a promising focus for unraveling these interactions. Deciphering interacting human-landscape feedbacks extends our traditional approach of considering humans as unidirectional drivers of change. Enormous challenges exist, however, in quantifying impact-feedback loops in landscapes with significant human alterations. This paper illustrates an example of human-landscape interactions following a wildfire in Colorado (USA) that elicited feedback responses. After the 2012 Waldo Canyon Fire, concerns for heightened flood potential and debris flows associated with post-fire hydrologic changes prompted local landowners to construct tall fences at the base of a burned watershed. These actions changed the sediment transport regime and promoted further landscape change and human responses in a positive feedback cycle. The interactions ultimately increase flood and sediment hazards, rather than dampening the effects of fire. A simple agent-based model, capable of integrating social and hydro-geomorphological data, demonstrates how such interacting impacts and feedbacks could be simulated. Challenges for fully capturing human-landscape feedback interactions include the identification of diffuse and subtle feedbacks at a range of scales, the availability of data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, and the varied metrics and data needed to represent both the physical and human systems. By collaborating with social scientists with expertise in the human causes of landscape change, as well as the human responses to those changes, geoscientists could more fully recognize and anticipate the coupled

  9. Support of a patient-specific therapeutical acoustic stimulation in tinnitus by numerical modeling.

    PubMed

    Haab, L; Scheerer, M; Ruckert, J; Hannemann, R; Strauss, D J

    2012-01-01

    The pathogenesis of tinnitus involves multiple hierarchical levels of auditory processing and appraisal of sensory saliency. Early tinnitus onset is most likely attributed to homeostatic plasticity in the periphery, while the chronification and decompensation are tightly linked to brain areas for the allocation of attentional resources, such as e.g., the thalamocortical feedback loops and the limbic system. Increased spontaneous firing after sensory deafferentation might be sufficient to generate a phantom perception, yet the question why not every peripheral hearing loss automatically elicits a tinnitus sensation is still to be addressed. Utilizing quantitative modeling of multiple hierarchical levels in the auditory pathway, we demonstrate the effects of lateral inhibition on increased spontaneous firing and the resulting elevation of firing regularity and synchronization of neural activity. The presented therapeutical approach is based on the idea of disrupting the heightened regularity of the neural population response in the tinnitus frequency range. This neural activity regularity depends on lateral dispersion of common noise and thus is susceptible for edge effects and might be influenced by a change in neural activity in bordering frequency ranges by fitted acoustical stimulation. We propose the use of patient specifically adapted tailor-made notched acoustic stimulation, utilizing modeling results for the optimal adjustment of the stimulation frequencies to archive a therapeutical edge-effect.

  10. Tutorial on beam-based feedback systems for linacs

    SciTech Connect

    Hendrickson, L.; Allison, S.; Gromme, T.; Grossberg, P.; Himel, T.; Krauter, K.; MacKenzie, R.; Ross, M.; Sass, R.; Shoaee, H.

    1994-08-01

    A generalized fast feedback system stabilizes beams in the SLC. It performs measurements and modifies actuator settings to control beam states such as position, angle, energy and intensity on a pulse to pulse basis. An adaptive cascade feature allows communication between a series of linac loops, avoiding overcorrection problems. The system is based on the state space formalism of digital control theory. Due to the database-driven design, new loops are added without requiring software modifications. Recent enhancements support the monitoring and control of nonlinear states such as beam phase using excitation techniques. In over three years of operation, the feedback system has grown from its original eight loops to more than fifty loops, and it has been invaluable in stabilizing the machine.

  11. Model-based feedback control of subsonic cavity flows: Control design

    NASA Astrophysics Data System (ADS)

    Yuan, Xin

    In this dissertation, we present and discuss development, implementation, and experimental results of reduced-order model based feedback control of subsonic cavity flows. Model based feedback control of subsonic flows have been studied and implemented by the flow control group at the Collaborative Center of Control Science (CCCS) at the Ohio State University (OSU). The team, composed of researchers from the departments of Electrical Engineering and Mechanical Engineering at the Ohio State, the Air Force Research Laboratory, and NASA Glenn Research Center, possesses synergistic capabilities in all of the required multidisciplinary areas of experimental data acquisition, computational flow simulation, low dimensional modeling, controller design, and experimental validation. The goal of the CCCS effort is to develop tools and methodologies for the use of closed-loop aerodynamic flow control to manipulate the flow over maneuvering air vehicles. The problem chosen for the initial study by the CCCS flow team is control of the resonant noise generated by subsonic flow past an open cavity. This phenomenon is characterized by a strong coupling between the flow dynamics and the flow-induced acoustic field that can lead to self-sustained resonance. Two approaches towards model development have been studied in this dissertation. One aims at representing the physical properties of the system by dynamical models in transfer function forms, referred to as the physics-based linear model in this dissertation. The other approach we have followed is based on proper orthogonal decomposition (POD) and Galerkin projection methods involving the flow governing equations, which is referred to as the nonlinear model or Galerkin model in the dissertation. Each model mentioned above can be further divided into two types: model derived from numerical simulation data and model derived from real time experimental data. Different types of feedback controllers have been designed for corresponding

  12. 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.

  13. Acoustic iridescence.

    PubMed

    Cox, Trevor J

    2011-03-01

    An investigation has been undertaken into acoustic iridescence, exploring how a device can be constructed which alter sound waves, in a similar way to structures in nature that act on light to produce optical iridescence. The main construction had many thin perforated sheets spaced half a wavelength apart for a specified design frequency. The sheets create the necessary impedance discontinuities to create backscattered waves, which then interfere to create strongly reflected sound at certain frequencies. Predictions and measurements show a set of harmonics, evenly spaced in frequency, for which sound is reflected strongly. And the frequency of these harmonics increases as the angle of observation gets larger, mimicking the iridescence seen in natural optical systems. Similar to optical systems, the reflections become weaker for oblique angles of reflection. A second construction was briefly examined which exploited a metamaterial made from elements and inclusions which were much smaller than the wavelength. Boundary element method predictions confirmed the potential for creating acoustic iridescence from layers of such a material.

  14. Acoustic transducer

    DOEpatents

    Drumheller, D.S.

    1997-12-30

    An acoustic transducer is described comprising a one-piece hollow mandrel into the outer surface of which is formed a recess with sides perpendicular to the central axis of the mandrel and separated by a first distance and with a bottom parallel to the central axis and within which recess are a plurality of washer-shaped discs of a piezoelectric material and at least one disc of a temperature-compensating material with the discs being captured between the sides of the recess in a pre-stressed interference fit, typically at 2,000 psi of compressive stress. The transducer also includes a power supply and means to connect to a measurement device. The transducer is intended to be used for telemetry between a measurement device located downhole in an oil or gas well and the surface. The transducer is of an construction that is stronger with fewer joints that could leak fluids into the recess holding the piezoelectric elements than is found in previous acoustic transducers. 4 figs.

  15. Acoustic transducer

    DOEpatents

    Drumheller, Douglas S.

    1997-01-01

    An acoustic transducer comprising a one-piece hollow mandrel into the outer surface of which is formed a recess with sides perpendicular to the central axis of the mandrel and separated by a first distance and with a bottom parallel to the central axis and within which recess are a plurality of washer-shaped discs of a piezoelectric material and at least one disc of a temperature-compensating material with the discs being captured between the sides of the recess in a pre-stressed interference fit, typically at 2000 psi of compressive stress. The transducer also includes a power supply and means to connect to a measurement device. The transducer is intended to be used for telemetry between a measurement device located downhole in an oil or gas well and the surface. The transducer is of an construction that is stronger with fewer joints that could leak fluids into the recess holding the piezoelectric elements than is found in previous acoustic transducers.

  16. Conic sectors for sampled-data feedback systems

    NASA Technical Reports Server (NTRS)

    Thompson, P. M.; Stein, G.; Athans, M.

    1983-01-01

    The conic-sector analysis of the closed-loop stability and robustness of a multivariable-analog-system controller based on sampled-data feedback compensation is investigated. Conic sectors and sampled-data feedback systems are defined, and the existence of a conic sector containing a sampled-data operator is established mathematically. An example is presented to prove that the conic sector is computable and gives sufficient conditions of closed-loop stability. A procedure for determining sampled-data-operator gain is also derived.

  17. 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...

  18. 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.

  19. Evoked brain responses are generated by feedback loops

    PubMed Central

    Garrido, Marta I.; Kilner, James M.; Kiebel, Stefan J.; Friston, Karl J.

    2007-01-01

    Neuronal responses to stimuli, measured electrophysiologically, unfold over several hundred milliseconds. Typically, they show characteristic waveforms with early and late components. It is thought that early or exogenous components reflect a perturbation of neuronal dynamics by sensory input bottom-up processing. Conversely, later, endogenous components have been ascribed to recurrent dynamics among hierarchically disposed cortical processing levels, top-down effects. Here, we show that evoked brain responses are generated by recurrent dynamics in cortical networks, and late components of event-related responses are mediated by backward connections. This evidence is furnished by dynamic causal modeling of mismatch responses, elicited in an oddball paradigm. We used the evidence for models with and without backward connections to assess their likelihood as a function of peristimulus time and show that backward connections are necessary to explain late components. Furthermore, we were able to quantify the contribution of backward connections to evoked responses and to source activity, again as a function of peristimulus time. These results link a generic feature of brain responses to changes in the sensorium and a key architectural component of functional anatomy; namely, backward connections are necessary for recurrent interactions among levels of cortical hierarchies. This is the theoretical cornerstone of most modern theories of perceptual inference and learning. PMID:18087046

  20. 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.

  1. 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.

  2. Aeolian processes and the bioshpere: Interactions and feedback loops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aeolian processes affect landform evolution, biogeochemical cycles, regional climate, human health, and desertification. The entrainment, transport and deposition of aeolian sediments are recognized as major drivers in the dynamics of the earth system and there is a growing interest in the scientif...

  3. Studies of the sensing mechanism in the tubuloglomerular feedback pathway.

    PubMed

    Wright, F S; Mandin, H; Persson, A E

    1982-08-01

    Two aspects of the single nephron feedback response previously observed by us have been reexamined. The first, the effect of modifying the composition of fluid used to perfuse the loop of Henle of a single nephron, was studied in rats by comparing flow-induced changes in stop-flow pressure (PSF) with three different perfusion solutions: artificial tubule fluid (ATF); 0.3 M mannitol (M); and mannitol plus 25 to 30 mM sodium chloride (M + E). The second, triggering of the feedback response by injection of ionic current into the distal tubule, was studied in similarly prepared rats by monitoring PSF while passing current. Increasing the rate of loop of Henle perfusion with either ATF or M + E resulted in similar decreases in PSF. In contrast, with M, changes in PSF were usually transient and if persistent were smaller than the changes observed with the other two solutions. When loops of Henle were perfused with ATF at a constant rate, injection of current into the early distal tubule making the lumen more negative resulted in decreases in PSF. Currents of opposite polarity caused no change in PSF if loop flow rate was low; these currents increased PSF if the loop flow rates had previously been high. Current-induced feedback responses were obtained with micropipette electrodes filled with either potassium chloride or lithium acetate. Addition of 10(-4) M furosemide blocked the current-induced feedback responses.

  4. Infant-Directed Speech Is Modulated by Infant Feedback

    ERIC Educational Resources Information Center

    Smith, Nicholas A.; Trainor, Laurel J.

    2008-01-01

    When mothers engage in infant-directed (ID) speech, their voices change in a number of characteristic ways, including adopting a higher overall pitch. Studies have examined these acoustical cues and have tested infants' preferences for ID speech. However, little is known about how these cues change with maternal sensitivity to infant feedback in…

  5. Improved feedback shift register

    NASA Technical Reports Server (NTRS)

    Perlman, M.

    1972-01-01

    Design of feedback shift register with three tap feedback decoding scheme is described. Application for obtaining sequence synchronization patterns is examined. Operation of the circuitry is described and drawings of the systems are included.

  6. Remote Robot Control With High Force-Feedback Gain

    NASA Technical Reports Server (NTRS)

    Kim, Won S.

    1993-01-01

    Improved scheme for force-reflecting hand control of remote robotic manipulator provides unprecedently high force-reflection gain, even when dissimilar master and slave arms used. Three feedback loops contained in remote robot control system exerting position-error-based force feedback and compliance control. Outputs of force and torque sensors on robot not used directly for force reflection, but for compliance control, while errors in position used to generate reflected forces.

  7. Particle tracking code of simulating global RF feedback

    SciTech Connect

    Mestha, L.K.

    1991-09-01

    It is well known in the control community'' that a good feedback controller design is deeply rooted in the physics of the system. For example, when accelerating the beam we must keep several parameters under control so that the beam travels within the confined space. Important parameters include the frequency and phase of the rf signal, the dipole field, and the cavity voltage. Because errors in these parameters will progressively mislead the beam from its projected path in the tube, feedback loops are used to correct the behavior. Since the feedback loop feeds energy to the system, it changes the overall behavior of the system and may drive it to instability. Various types of controllers are used to stabilize the feedback loop. Integrating the beam physics with the feedback controllers allows us to carefully analyze the beam behavior. This will not only guarantee optimal performance but will also significantly enhance the ability of the beam control engineer to deal effectively with the interaction of various feedback loops. Motivated by this theme, we developed a simple one-particle tracking code to simulate particle behavior with feedback controllers. In order to achieve our fundamental objective, we can ask some key questions: What are the input and output parameters How can they be applied to the practical machine How can one interface the rf system dynamics such as the transfer characteristics of the rf cavities and phasing between the cavities Answers to these questions can be found by considering a simple case of a single cavity with one particle, tracking it turn-by-turn with appropriate initial conditions, then introducing constraints on crucial parameters. Critical parameters are rf frequency, phase, and amplitude once the dipole field has been given. These are arranged in the tracking code so that we can interface the feedback system controlling them.

  8. Improvements To Progressive Wave Tube Performance Through Closed-Loop Control

    NASA Technical Reports Server (NTRS)

    Rizzi, Stephen A.

    2000-01-01

    This report documents recent improvements to the acoustic and thermal control systems of the Thermal Acoustic Fatigue Apparatus (TAFA), a progressive wave tube test facility at the NASA Langley Research Center, Hampton, Virginia. A brief summary of past acoustic performance is given first to serve as a basis for comparison with the new performance data using a multiple-input, closed-loop, narrow-band controller. Performance data in the form of test section acoustic power spectral densities and coherence are presented in three of six facility configurations for a variety of input spectra. Tested spectra include uniform, two cases of pink noise, three cases of narrow-band random, a simulated launch payload bay environment for an expendable launch vehicle, and a simulated external acoustic load for the aft section of a reusable launch vehicle. In addition, a new closed-loop temperature controller and thermocouple data acquisition system are described.

  9. 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…

  10. 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…

  11. Passage Feedback with IRIS.

    ERIC Educational Resources Information Center

    Yang, Kiduk; Maglaughlin, Kelly L.; Newby, Gregory B.

    2001-01-01

    Compares a user-defined passage feedback system to a document feedback system for information retrieval, based on TREC (Text Retrieval Conference) guidelines. Highlights include a description of IRIS, an interactive retrieval system; text processing; ranking; term weights; feedback models, including the adaptive linear model; and suggestions for…

  12. 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…

  13. 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

  14. Multifunctional design of inertially-actuated velocity feedback controllers.

    PubMed

    Elliott, S J; Rohlfing, J; Gardonio, P

    2012-02-01

    The vibration of a structure can be controlled using either a passive tuned mass damper or using an active vibration control system. In this paper, the design of a multifunctional system is discussed, which uses an inertial actuator as both a tuned mass damper and as an element in a velocity feedback control loop. The natural frequency of the actuator would normally need to be well below that of the structure under control to give a stable velocity feedback controller, whereas it needs to be close to the natural frequency of a dominant structural resonance to act as an effective tuned mass damper. A compensator is used in the feedback controller here to allow stable feedback operation even when the actuator natural frequency is close to that of a structural mode. A practical example of such a compensator is described for a small inertial actuator, which is then used to actively control the vibrations both on a panel and on a beam. The influence of the actuator as a passive tuned mass damper can be clearly seen before the feedback loop is closed, and broadband damping is then additionally achieved by closing the velocity feedback loop.

  15. The role of auditory feedback in vocal learning and maintenance

    PubMed Central

    Tschida, Katherine; Mooney, Richard

    2011-01-01

    Auditory experience is critical for the acquisition and maintenance of learned vocalizations in both humans and songbirds. Despite the central role of auditory feedback in vocal learning and maintenance, where and how auditory feedback affects neural circuits important to vocal control remain poorly understood. Recent studies of singing birds have uncovered neural mechanisms by which feedback perturbations affect vocal plasticity and also have identified feedback-sensitive neurons at or near sites of auditory and vocal motor interaction. Additionally, recent studies in marmosets have underscored that even in the absence of vocal learning, vocalization remains flexible in the face of changing acoustical environments, pointing to rapid interactions between auditory and vocal motor systems. Finally, recent studies show that a juvenile songbird’s initial auditory experience of a song model has long-lasting effects on sensorimotor neurons important to vocalization, shedding light on how auditory memories and feedback interact to guide vocal learning. PMID:22137567

  16. Acoustic cryocooler

    DOEpatents

    Swift, Gregory W.; Martin, Richard A.; Radenbaugh, Ray

    1990-01-01

    An acoustic cryocooler with no moving parts is formed from a thermoacoustic driver (TAD) driving a pulse tube refrigerator (PTR) through a standing wave tube. Thermoacoustic elements in the TAD are spaced apart a distance effective to accommodate the increased thermal penetration length arising from the relatively low TAD operating frequency in the range of 15-60 Hz. At these low operating frequencies, a long tube is required to support the standing wave. The tube may be coiled to reduce the overall length of the cryocooler. One or two PTR's are located on the standing wave tube adjacent antinodes in the standing wave to be driven by the standing wave pressure oscillations. It is predicted that a heat input of 1000 W at 1000 K will maintian a cooling load of 5 W at 80 K.

  17. Acoustic transducer

    DOEpatents

    Drumheller, Douglas S.

    2000-01-01

    An active acoustic transducer tool for use down-hole applications. The tool includes a single cylindrical mandrel including a shoulder defining the boundary of a narrowed portion over which is placed a sandwich-style piezoelectric tranducer assembly. The piezoelectric transducer assembly is prestressed by being placed in a thermal interference fit between the shoulder of the mandrel and the base of an anvil which is likewise positioned over the narrower portion of the mandrel. In the preferred embodiment, assembly of the tool is accomplished using a hydraulic jack to stretch the mandrel prior to emplacement of the cylindrical sandwich-style piezoelectric transducer assembly and anvil. After those elements are positioned and secured, the stretched mandrel is allowed to return substantially to its original (pre-stretch) dimensions with the result that the piezoelectric transducer elements are compressed between the anvil and the shoulder of the mandrel.

  18. Acoustic telemetry.

    SciTech Connect

    Drumheller, Douglas Schaeffer; Kuszmaul, Scott S.

    2003-08-01

    Broadcasting messages through the earth is a daunting task. Indeed, broadcasting a normal telephone conversion through the earth by wireless means is impossible with todays technology. Most of us don't care, but some do. Industries that drill into the earth need wireless communication to broadcast navigation parameters. This allows them to steer their drill bits. They also need information about the natural formation that they are drilling. Measurements of parameters such as pressure, temperature, and gamma radiation levels can tell them if they have found a valuable resource such as a geothermal reservoir or a stratum bearing natural gas. Wireless communication methods are available to the drilling industry. Information is broadcast via either pressure waves in the drilling fluid or electromagnetic waves in the earth and well tubing. Data transmission can only travel one way at rates around a few baud. Given that normal Internet telephone modems operate near 20,000 baud, these data rates are truly very slow. Moreover, communication is often interrupted or permanently blocked by drilling conditions or natural formation properties. Here we describe a tool that communicates with stress waves traveling through the steel drill pipe and production tubing in the well. It's based on an old idea called Acoustic Telemetry. But what we present here is more than an idea. This tool exists, it's drilled several wells, and it works. Currently, it's the first and only acoustic telemetry tool that can withstand the drilling environment. It broadcasts one way over a limited range at much faster rates than existing methods, but we also know how build a system that can communicate both up and down wells of indefinite length.

  19. Observation of oscillations in coronal loops

    NASA Astrophysics Data System (ADS)

    De Moortel, I.; Walsh, R. W.; Ireland, J.

    2000-10-01

    High cadence TRACE data (JOP 83) in the 171 Å bandpass are used to report on several examples of outward propagating oscillations in the footpoints of large diffuse coronal loop structures close to active regions. The disturbances travel outward with a propagation speed between 70 and 160 km s-1. The variations in intensity are of the order of 2%-4%, compared to the background brightness and these get weaker as the disturbance propagates along the structure. From a wavelet analysis at different positions along the structures, periods in the 200-400 seconds range are found. It is suggested that these oscillations are slow magneto-acoustic waves propagating along the loop, carrying an estimated energy flux of 4×102 ergs cm-2 s-1. .

  20. Fishbone-like instability in a looped-tube thermoacoustic engine.

    PubMed

    Yu, Zhibin; Jaworski, Artur J; Abduljalil, Abdulrahman S

    2010-10-01

    Quasi-periodic bursts of acoustic oscillations were observed during the start-up process in a looped-tube thermoacoustic engine. The acoustic oscillations have a constant frequency of 111 Hz, while the bursts have "quasi-periods" in the order of 14-25 s. The quasi-periodic bursts show a new mode of amplitude growth in this thermoacoustic engine. The envelope of the acoustic oscillations has a fishbone-like shape. The nature of the observed fishbone-like instabilities suggests a strong interaction between the acoustic and temperature field.

  1. A multi-channel feedback algorithm for the development of active liners to reduce noise in flow duct applications

    NASA Astrophysics Data System (ADS)

    Mazeaud, B.; Galland, M.-A.

    2007-10-01

    The present paper deals with the design and development of the active part of a hybrid acoustic treatment combining porous material properties and active control techniques. Such an acoustic system was developed to reduce evolutionary tones in flow duct applications. Attention was particularly focused on the optimization process of the controller part of the hybrid cell. A piezo-electric transducer combining efficiency and compactness was selected as a secondary source. A digital adaptive feedback control algorithm was specially developed in order to operate independently cell by cell, and to facilitate a subsequent increase in the liner surface. An adaptive bandpass filter was used to prevent the development of instabilities due to the coupling occurring between cells. Special care was taken in the development of such systems for time-varying primary signals. An automatic frequency detection loop was therefore introduced in the control algorithm, enabling the continuous adaptation of the bandpass filtering. The multi-cell structure was experimentally validated for a four-cell system located on a duct wall in the presence of flow. Substantial noise reduction was obtained throughout the 0.7-2.5 kHz frequency range, with flow velocities up to 50 m/s.

  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. 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.

  4. The role of proprioceptive feedback in Parkinsonian resting tremor.

    PubMed

    Govil, Nikhil; Akinin, Abraham; Ward, Samuel; Snider, Joseph; Plank, Markus; Cauwenberghs, Gert; Poizner, Howard

    2013-01-01

    In this paper we use a closed-loop force feedback system to investigate the effect of altering proprioceptive feedback on EEG and resting tremor in Parkinson's Disease. A velocity dependent counterforce simulating viscous friction was provided by haptic robots with simultaneous recording of kinematics, EMG and EEG while a patient was on and off dopaminergic medication' We were able to reduce the amplitude of the tremor. We also showed that force feedback shifts the center of EEG-EMG coherence posteriorly toward the somatosensory regions, which may have ramifications for noninvasive therapies.

  5. MiR-208a stimulates the cocktail of SOX2 and β-catenin to inhibit the let-7 induction of self-renewal repression of breast cancer stem cells and formed miR208a/let-7 feedback loop via LIN28 and DICER1.

    PubMed

    Sun, Xin; Jiang, Shiwen; Liu, Jian; Wang, Huangzhen; Zhang, Yiwen; Tang, Shou-Ching; Wang, Jichang; Du, Ning; Xu, Chongwen; Wang, Chenguang; Qin, Sida; Zhang, Jia; Liu, Dapeng; Zhang, Yunfeng; Li, Xiaojun; Wang, Jiansheng; Dong, Jun; Wang, Xin; Xu, Shaohua; Tao, Zhen; Xu, Fei; Zhou, Jie; Wang, Tao; Ren, Hong

    2015-10-20

    MiR-208a stimulates cardiomyocyte hypertrophy, fibrosis and β-MHC (β-myosin heavy chain) expression, being involved in cardiovascular diseases. Although miR-208a is known to play a role in cardiovascular diseases, its role in cancer and cancer stem cells (CSCs) remains uncertain. We identified an inverse relationship between miR-208a and let-7a in breast cancer specimens, and found that SOX2, β-catenin and LIN28 are highly expressed in patients with advanced breast cancer opposed to lesser grades. Further, we isolated ALDH1+ CSCs from ZR75-1 and MDA-MB-231 (MM-231) breast cancer cell lines to test the role of miR-208a in breast CSCs (BrCSCs). Our studies showed that overexpression of miR-208a in these cells strongly promoted the proportion of ALDH1+ BrCSCs and continuously stimulated the self-renewal ability of BrCSCs. By using siRNAs of SOX2 and/or β-catenin, we found that miR-208a increased LIN28 through stimulation of both SOX2 and β-catenin. The knockdown of either SOX2 or β-catenin only partially attenuated the functions of miR-208a. Let-7a expression was strongly inhibited in miR-208a overexpressed cancer cells, which was achieved by miR-208a induction of LIN28, and the restoration of let-7a significantly inhibited the miR-208a induction of the number of ALDH1+ cells, inhibiting the propagations of BrCSCs. In let-7a overexpressed ZR75-1 and MM-231 cells, DICER1 activity was significantly inhibited with decreased miR-208a. Let-7a failed to decrease miR-208a expression in ZR75-1 and MM-231 cells with DICER1 knockdown. Our research revealed the mechanisms through which miR-208a functioned in breast cancer and BrCSCs, and identified the miR-208a-SOX2/β-catenin-LIN28-let-7a-DICER1 regulatory feedback loop in regulations of stem cells renewal.

  6. MiR-208a stimulates the cocktail of SOX2 and β-catenin to inhibit the let-7 induction of self-renewal repression of breast cancer stem cells and formed miR208a/let-7 feedback loop via LIN28 and DICER1

    PubMed Central

    Liu, Jian; Wang, Huangzhen; Zhang, Yiwen; Tang, Shou-Ching; Wang, Jichang; Du, Ning; Xu, Chongwen; Wang, Chenguang; Qin, Sida; Zhang, Jia; Liu, Dapeng; Zhang, Yunfeng; Li, Xiaojun; Wang, Jiansheng; Dong, Jun; Wang, Xin; Xu, Shaohua; Tao, Zhen; Xu, Fei; Zhou, Jie; Wang, Tao; Ren, Hong

    2015-01-01

    MiR-208a stimulates cardiomyocyte hypertrophy, fibrosis and β-MHC (β-myosin heavy chain) expression, being involved in cardiovascular diseases. Although miR-208a is known to play a role in cardiovascular diseases, its role in cancer and cancer stem cells (CSCs) remains uncertain. We identified an inverse relationship between miR-208a and let-7a in breast cancer specimens, and found that SOX2, β-catenin and LIN28 are highly expressed in patients with advanced breast cancer opposed to lesser grades. Further, we isolated ALDH1+ CSCs from ZR75–1 and MDA-MB-231 (MM-231) breast cancer cell lines to test the role of miR-208a in breast CSCs (BrCSCs). Our studies showed that overexpression of miR-208a in these cells strongly promoted the proportion of ALDH1+ BrCSCs and continuously stimulated the self-renewal ability of BrCSCs. By using siRNAs of SOX2 and/or β-catenin, we found that miR-208a increased LIN28 through stimulation of both SOX2 and β-catenin. The knockdown of either SOX2 or β-catenin only partially attenuated the functions of miR-208a. Let-7a expression was strongly inhibited in miR-208a overexpressed cancer cells, which was achieved by miR-208a induction of LIN28, and the restoration of let-7a significantly inhibited the miR-208a induction of the number of ALDH1+ cells, inhibiting the propagations of BrCSCs. In let-7a overexpressed ZR75–1 and MM-231 cells, DICER1 activity was significantly inhibited with decreased miR-208a. Let-7a failed to decrease miR-208a expression in ZR75–1 and MM-231 cells with DICER1 knockdown. Our research revealed the mechanisms through which miR-208a functioned in breast cancer and BrCSCs, and identified the miR-208a-SOX2/β-catenin-LIN28-let-7a-DICER1 regulatory feedback loop in regulations of stem cells renewal. PMID:26460550

  7. 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.

  8. RF power recovery feedback circulator

    DOEpatents

    Sharamentov, Sergey I [Bolingbrook, IL

    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.

  9. Auditory feedback modulates development of kitten vocalizations.

    PubMed

    Hubka, Peter; Konerding, Wiebke; Kral, Andrej

    2015-07-01

    Effects of hearing loss on vocal behavior are species-specific. To study the impact of auditory feedback on feline vocal behavior, vocalizations of normal-hearing, hearing-impaired (white) and congenitally deaf (white) cats were analyzed at around weaning age. Eleven animals were placed in a soundproof booth for 30 min at different ages, from the first to the beginning of the fourth postnatal month, every 2 weeks of life. In total, 13,874 vocalizations were analyzed using an automated procedure. Firstly, vocalizations were detected and segmented, with voiced and unvoiced vocalizations being differentiated. The voiced isolation calls ('meow') were further analyzed. These vocalizations showed developmental changes affecting several parameters in hearing controls, whereas the developmental sequence was delayed in congenitally deaf cats. In hearing-impaired and deaf animals, we observed differences both in vocal behavior (loudness and duration) and in the calls' acoustic structure (fundamental frequency and higher harmonics). The fundamental frequency decreased with age in all groups, most likely due to maturation of the vocal apparatus. In deaf cats, however, other aspects of the acoustic structure of the vocalizations did not fully mature. The harmonic ratio (i.e., frequency of first harmonic divided by fundamental frequency) was higher and more variable in deaf cats than in the other study groups. Auditory feedback thus affects the acoustic structure of vocalizations and their ontogenetic development. The study suggests that both the vocal apparatus and its neuronal motor control are subject to maturational processes, whereas the latter is additionally dependent on auditory feedback in cats.

  10. 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.

  11. 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…

  12. 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…

  13. Stabilization of a flexible body (hoop-column) antenna by feedback control law

    NASA Technical Reports Server (NTRS)

    Choudhury, A.

    1984-01-01

    Feedback control laws are presented for stabilization models of a hoop/column antenna. A brief review of linear and nonlinear feedback control laws is included. A method that is computable on a microprocessor and assures closed loop stability is explained and compared to a linear control law model.

  14. Acoustic source for generating an acoustic beam

    DOEpatents

    Vu, Cung Khac; Sinha, Dipen N.; Pantea, Cristian

    2016-05-31

    An acoustic source for generating an acoustic beam includes a housing; a plurality of spaced apart piezo-electric layers disposed within the housing; and a non-linear medium filling between the plurality of layers. Each of the plurality of piezoelectric layers is configured to generate an acoustic wave. The non-linear medium and the plurality of piezo-electric material layers have a matching impedance so as to enhance a transmission of the acoustic wave generated by each of plurality of layers through the remaining plurality of layers.

  15. Canonical Acoustics and Its Application to Surface Acoustic Wave on Acoustic Metamaterials

    NASA Astrophysics Data System (ADS)

    Shen, Jian Qi

    2016-08-01

    In a conventional formalism of acoustics, acoustic pressure p and velocity field u are used for characterizing acoustic waves propagating inside elastic/acoustic materials. We shall treat some fundamental problems relevant to acoustic wave propagation alternatively by using canonical acoustics (a more concise and compact formalism of acoustic dynamics), in which an acoustic scalar potential and an acoustic vector potential (Φ ,V), instead of the conventional acoustic field quantities such as acoustic pressure and velocity field (p,u) for characterizing acoustic waves, have been defined as the fundamental variables. The canonical formalism of the acoustic energy-momentum tensor is derived in terms of the acoustic potentials. Both the acoustic Hamiltonian density and the acoustic Lagrangian density have been defined, and based on this formulation, the acoustic wave quantization in a fluid is also developed. Such a formalism of acoustic potentials is employed to the problem of negative-mass-density assisted surface acoustic wave that is a highly localized surface bound state (an eigenstate of the acoustic wave equations). Since such a surface acoustic wave can be strongly confined to an interface between an acoustic metamaterial (e.g., fluid-solid composite structures with a negative dynamical mass density) and an ordinary material (with a positive mass density), it will give rise to an effect of acoustic field enhancement on the acoustic interface, and would have potential applications in acoustic device design for acoustic wave control.

  16. What Is an Acoustic Neuroma

    MedlinePlus

    ... ANAUSA.org Connect with us! What is an Acoustic Neuroma? Each heading slides to reveal information. Important ... Acoustic Neuroma Important Points To Know About an Acoustic Neuroma An acoustic neuroma, also called a vestibular ...

  17. Beyond singular values and loop shapes

    NASA Technical Reports Server (NTRS)

    Stein, G.

    1985-01-01

    The status of singular value loop-shaping as a design paradigm for multivariable feedback systems is reviewed. It shows that this paradigm is an effective design tool whenever the problem specifications are spacially round. The tool can be arbitrarily conservative, however, when they are not. This happens because singular value conditions for robust performance are not tight (necessary and sufficient) and can severely overstate actual requirements. An alternate paradign is discussed which overcomes these limitations. The alternative includes a more general problem formulation, a new matrix function mu, and tight conditions for both robust stability and robust performance. The state of the art currently permits analysis of feedback systems within this new paradigm. Synthesis remains a subject of research.

  18. 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.

  19. Updating the programming of a precision grip is a function of recent history of available feedback.

    PubMed

    Whitwell, Robert L; Goodale, Melvyn A

    2009-04-01

    In a recent study (Whitwell et al. in Exp Brain Res 185:111-119, 2008), we showed that the visuomotor system is "cognitively impenetrable" to the extent that explicit predictive knowledge of the availability of visual feedback on an upcoming trial fails to optimize grasping. The results suggested that the effects of trial history, rather than the anticipatory knowledge of the nature of an upcoming trial, plays the most significant role in how the availability of visual feedback is exploited by the visuomotor system when programming grip aperture (e.g., opening the hand wider when visual feedback is unavailable). Here, we provide direct evidence that trial history indeed plays a critical role in the programming of grip aperture. Twelve individuals grasped objects of three different sizes placed at one of two distances either with or without visual feedback of the hand and object (closed- or open-loop trials, respectively). Runs of four consecutive closed- or open-loop trials were interleaved with sequences of closed and open-loop trials that alternated back and forth from trial to trial. Peak grip aperture (PGA) decreased linearly with successive closed-loop trials and increased linearly with successive open-loop trials. We also compared PGA for trials that were preceded by a run of four consecutive closed- (or open-loop) trials with trials that were preceded by only one closed- (or open-loop) trial. This analysis indicated that consistency in the runs of closed- or open-loop trials significantly reduced the effect of the availability of feedback on grasping in the trial following the run. We conclude that while the margin of error observed in precision grasping is largely a function of the availability of visual feedback on the current trial, it is evidently also a function of the recent history of the availability of visual feedback on previous trials.

  20. 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.