Science.gov

Sample records for voltage feedback loop

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

    NASA Astrophysics Data System (ADS)

    Ahmed, Tarek; Noro, Osamu; Nakaoka, Mutsuo

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

  2. Feedback loop compensates for rectifier nonlinearity

    NASA Technical Reports Server (NTRS)

    1966-01-01

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

  3. Monitoring Digital Closed-Loop Feedback Systems

    NASA Technical Reports Server (NTRS)

    Katz, Richard; Kleyner, Igor

    2011-01-01

    A technique of monitoring digital closed-loop feedback systems has been conceived. The basic idea is to obtain information on the performances of closed-loop feedback circuits in such systems to aid in the determination of the functionality and integrity of the circuits and of performance margins. The need for this technique arises as follows: Some modern digital systems include feedback circuits that enable other circuits to perform with precision and are tolerant of changes in environment and the device s parameters. For example, in a precision timing circuit, it is desirable to make the circuit insensitive to variability as a result of the manufacture of circuit components and to the effects of temperature, voltage, radiation, and aging. However, such a design can also result in masking the indications of damaged and/or deteriorating components. The present technique incorporates test circuitry and associated engineering-telemetry circuitry into an embedded system to monitor the closed-loop feedback circuits, using spare gates that are often available in field programmable gate arrays (FPGAs). This technique enables a test engineer to determine the amount of performance margin in the system, detect out of family circuit performance, and determine one or more trend(s) in the performance of the system. In one system to which the technique has been applied, an ultra-stable oscillator is used as a reference for internal adjustment of 12 time-to-digital converters (TDCs). The feedback circuit produces a pulse-width-modulated signal that is fed as a control input into an amplifier, which controls the circuit s operating voltage. If the circuit s gates are determined to be operating too slowly or rapidly when their timing is compared with that of the reference signal, then the pulse width increases or decreases, respectively, thereby commanding the amplifier to increase or reduce, respectively, its output level, and "adjust" the speed of the circuits. The nominal

  4. UWB communication receiver feedback loop

    DOEpatents

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

    2007-12-04

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

  5. The ionospheric outflow feedback loop

    NASA Astrophysics Data System (ADS)

    Moore, T. E.; Fok, M.-C.; Garcia-Sage, K.

    2014-08-01

    Following a long period of observation and investigation beginning in the early 1970s, it has been firmly established that Earth's magnetosphere is defined as much by the geogenic plasma within it as by the geomagnetic field. This plasma is not confined to the ionosphere proper, defined as the region within a few density scale heights of the F-region plasma density peak. Rather, it fills the flux tubes on which it is created, and circulates throughout the magnetosphere in a pattern driven by solar wind plasma that becomes magnetically connected to the ionosphere by reconnection through the dayside magnetopause. Under certain solar wind conditions, plasma and field energy is stored in the magnetotail rather than being smoothly recirculated back to the dayside. Its release into the downstream solar wind is produced by magnetotail disconnection of stored plasma and fields both continuously and in the form of discrete plasmoids, with associated generation of energetic Earthward-moving bursty bulk flows and injection fronts. A new generation of global circulation models is showing us that outflowing ionospheric plasmas, especially O+, load the system in a different way than the resistive F-region load of currents dissipating energy in the plasma and atmospheric neutral gas. The extended ionospheric load is reactive to the primary dissipation, forming a time-delayed feedback loop within the system. That sets up or intensifies bursty transient behaviors that would be weaker or absent if the ionosphere did not “strike back” when stimulated. Understanding this response appears to be a necessary, if not sufficient, condition for us to gain accurate predictive capability for space weather. However, full predictive understanding of outflow and incorporation into global simulations requires a clear observational and theoretical identification of the causal mechanisms of the outflows. This remains elusive and requires a dedicated mission effort.

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

    NASA Technical Reports Server (NTRS)

    Rippy, R. R. (Inventor)

    1976-01-01

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

  7. 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.

  8. Linking Nutrients to Growth through a Positive Feedback Loop.

    PubMed

    Palu, Rebecca A S; Thummel, Carl S

    2015-11-01

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

  9. Development of Murray Loop Bridge for High Induced Voltage

    NASA Astrophysics Data System (ADS)

    Isono, Shigeki; Kawasaki, Katsutoshi; Kobayashi, Shin-Ichi; Ishihara, Hayato; Chiyajo, Kiyonobu

    In the case of the cable fault that ground fault resistance is less than 10MΩ, Murray Loop Bridge is excellent as a fault locator in location accuracy and the convenience. But, when the induction of several hundred V is taken from the single core cable which adjoins it, a fault location with the high voltage Murray Loop Bridge becomes difficult. Therefore, we developed Murray Loop Bridge, which could be applied even when the induced voltage of several hundred V occurs in the measurement cable. The evaluation of the fault location accuracy was done with the developed prototype by the actual line and the training equipment.

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

    PubMed Central

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

    2014-01-01

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

  11. Equilibria and stability of a class of positive feedback loops.

    PubMed

    López-Caamal, Fernando; Middleton, Richard H; Huber, Heinrich J

    2014-02-01

    Positive feedback loops are common regulatory elements in metabolic and protein signalling pathways. The length of such feedback loops determines stability and sensitivity to network perturbations. Here we provide a mathematical analysis of arbitrary length positive feedback loops with protein production and degradation. These loops serve as an abstraction of typical regulation patterns in protein signalling pathways. We first perform a steady state analysis and, independently of the chain length, identify exactly two steady states that represent either biological activity or inactivity. We thereby provide two formulas for the steady state protein concentrations as a function of feedback length, strength of feedback, as well as protein production and degradation rates. Using a control theory approach, analysing the frequency response of the linearisation of the system and exploiting the Small Gain Theorem, we provide conditions for local stability for both steady states. Our results demonstrate that, under some parameter relationships, once a biological meaningful on steady state arises, it is stable, while the off steady state, where all proteins are inactive, becomes unstable. We apply our results to a three-tier feedback of caspase activation in apoptosis and demonstrate how an intermediary protein in such a loop may be used as a signal amplifier within the cascade. Our results provide a rigorous mathematical analysis of positive feedback chains of arbitrary length, thereby relating pathway structure and stability. PMID:23358701

  12. 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.

  13. Slow dynamics of postural sway are in the feedback loop.

    PubMed

    Kiemel, Tim; Oie, Kelvin S; Jeka, John J

    2006-03-01

    Postural sway is considered to have two fundamental stochastic components, a slow nonoscillatory component and a faster damped-oscillatory component. The slow component has been shown to account for the majority of sway variance during quiet stance. Postural control is generally viewed as a feedback loop in which sway is detected by sensory systems and appropriate motor commands are generated to stabilize the body's orientation. Whereas the mechanistic source for the damped-oscillatory sway component is most likely feedback control of an inverted pendulum, the underlying basis for the slow component is less clear. We investigated whether the slow process was inside or outside the feedback loop by providing standing subjects with sum-of-sines visual motion. Linear stochastic models were fit to the experimental sway trajectories to determine the stochastic structure of sway as well as the transfer function from visual motion to sway. The results supported a fifth-order stochastic model, consisting of a slow process and two damped-oscillatory components. Importantly, the slow process was determined to be inside the feedback loop. This supports the hypothesis that the slow component is due to errors in state estimation because state estimation is inside the feedback loop rather than a moving reference point or an exploratory process outside the feedback loop. PMID:16192341

  14. 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.

  15. 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.

  16. 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.

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

    SciTech Connect

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

    1994-04-01

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

  18. The impact of hypervigilance: evidence for a forward feedback loop.

    PubMed

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

    2014-03-01

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

  19. The optimal loop gain design for the spectral linewidth reduction in an electrical feedback semiconductor laser

    SciTech Connect

    Li, L. )

    1991-08-01

    In this paper the design rule of the optimal feedback loop gain for the spectral linewidth reduction in a semiconductor laser with electrical feedback is presented using the model of self-heterodyne type electrical feedback. Due to the intensity noise in the feedback signal, there is an optimal value for the feedback loop gain to reduce the spectral linewidth of a semiconductor laser in a given feedback condition.

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  1. Closed loop kinesthetic feedback for postural control rehabilitation.

    PubMed

    Vérité, Fabien; Bachta, Wael; Morel, Guillaume

    2014-01-01

    Postural control rehabilitation may benefit from the use of smart devices providing biofeedback. This approach consists of increasing the patients perception of their postural state. Namely, postural state is monitored and fed back in real time to the patients through one or more sensory channels. This allows implementing rehabilitation exercises where the patients control their posture with the help of additional sensory inputs. In this paper, a closed loop control of the Center-Of-Pressure (CoP) based on kinesthetic feedback is proposed as a new form of biofeedback. The motion of a one Degree of Freedom (DoF) translational device, lightly touched by the patient's forefinger, is servoed to the patient's CoP position extracted from the measurements of a force plate on which he/she stands. As a result, the patient's CoP can be controllably displaced. A first set of experiments is used to prove the feasibility of this closed-loop control under ideal conditions favoring the perception of the kinesthetic feedback, while the subject is totally unaware of the context. A second set of experiments is then proposed to evaluate the robustness of this approach under experimental conditions that are more realistic with regards to the clinical context of a rehabilitation program involving biofeedback-based exercises. PMID:24968379

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

    NASA Astrophysics Data System (ADS)

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

    2002-12-01

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

  3. Practical Loop-Shaping Design of Feedback Control Systems

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2010-01-01

    An improved methodology for designing feedback control systems has been developed based on systematically shaping the loop gain of the system to meet performance requirements such as stability margins, disturbance attenuation, and transient response, while taking into account the actuation system limitations such as actuation rates and range. Loop-shaping for controls design is not new, but past techniques do not directly address how to systematically design the controller to maximize its performance. As a result, classical feedback control systems are designed predominantly using ad hoc control design approaches such as proportional integral derivative (PID), normally satisfied when a workable solution is achieved, without a good understanding of how to maximize the effectiveness of the control design in terms of competing performance requirements, in relation to the limitations of the plant design. The conception of this improved methodology was motivated by challenges in designing control systems of the types needed for supersonic propulsion. But the methodology is generally applicable to any classical control-system design where the transfer function of the plant is known or can be evaluated. In the case of a supersonic aerospace vehicle, a major challenge is to design the system to attenuate anticipated external and internal disturbances, using such actuators as fuel injectors and valves, bypass doors, and ramps, all of which are subject to limitations in actuator response, rates, and ranges. Also, for supersonic vehicles, with long slim type of structures, coupling between the engine and the structural dynamics can produce undesirable effects that could adversely affect vehicle stability and ride quality. In order to design distributed controls that can suppress these potential adverse effects, within the full capabilities of the actuation system, it is important to employ a systematic control design methodology such as this that can maximize the

  4. On the dynamics of delayed neural feedback loops

    NASA Astrophysics Data System (ADS)

    Brandt, Sebastian F.

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

  5. Ultrasensitive gene regulation by positive feedback loops in nucleosome modification.

    PubMed

    Sneppen, Kim; Micheelsen, Mille A; Dodd, Ian B

    2008-01-01

    Eukaryotic transcription involves the synergistic interaction of many different proteins. However, the question remains how eukaryotic promoters achieve ultrasensitive or threshold responses to changes in the concentration or activity of a single transcription factor (TF). We show theoretically that by recruiting a histone-modifying enzyme, a TF binding non-cooperatively to a single site can change the balance between opposing positive feedback loops in histone modification to produce a large change in gene expression in response to a small change in concentration of the TF. This mechanism can also generate bistable promoter responses, allowing a gene to be on in some cells and off in others, despite the cells being in identical conditions. In addition, the system provides a simple means by which the activities of many TFs could be integrated at a promoter. PMID:18414483

  6. Regulatory feedback loop between TP73 and TRIM32.

    PubMed

    Gonzalez-Cano, L; Hillje, A-L; Fuertes-Alvarez, S; Marques, M M; Blanch, A; Ian, R W; Irwin, M S; Schwamborn, J C; Marín, M C

    2013-01-01

    The p73 transcription factor is one of the members of the p53 family of tumor suppressors with unique biological functions in processes like neurogenesis, embryonic development and differentiation. For this reason, p73 activity is tightly regulated by multiple mechanisms, including transcription and post-translational modifications. Here, we identified a novel regulatory loop between TAp73 and the E3 ubiquitin ligase tripartite motif protein 32 (TRIM32). TRIM32, a new direct p73 transcriptional target in the context of neural progenitor cells, is differentially regulated by p73. Although TAp73 binds to the TRIM32 promoter and activates its expression, TAp73-induced TRIM32 expression is efficiently repressed by DNp73. TRIM32 in turn physically interacts with TAp73 and promotes its ubiquitination and degradation, impairing p73-dependent transcriptional activity. This mutual regulation between p73 and TRIM32 constitutes a novel feedback loop, which might have important implications in central nervous system development as well as relevance in oncogenesis, and thus emerges as a possible therapeutic target. PMID:23828567

  7. 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

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

    SciTech Connect

    Alexeff, I.; Rader, M.

    1995-05-01

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

  9. 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)…

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

    SciTech Connect

    Huang, G.; Byrd, J. M.

    2006-11-20

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

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

    PubMed

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

    2015-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  13. A Feedback Loop between Inflammation and Zn Uptake

    PubMed Central

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

    2016-01-01

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

  14. 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

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

    PubMed

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

    2014-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

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

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

    SciTech Connect

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

    2012-01-01

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

  18. 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.

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

    PubMed

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

    2015-10-01

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

  20. 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

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

    ERIC Educational Resources Information Center

    Barker, Martin; Pinard, Michelle

    2014-01-01

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

  2. 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.

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

    DOE PAGESBeta

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

    2015-12-01

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

  4. 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…

  5. 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.

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

    PubMed

    Sriram, K; Soliman, Sylvain; Fages, François

    2009-05-01

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

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

    NASA Technical Reports Server (NTRS)

    Hoelscher, Brian R.; Vadali, Srinvas R.

    1993-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Stalford, Harold

    1988-01-01

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

  9. Revealing a Two-Loop Transcriptional Feedback Mechanism in the Cyanobacterial Circadian Clock

    PubMed Central

    Hertel, Stefanie; Brettschneider, Christian; Axmann, Ilka M.

    2013-01-01

    Molecular genetic studies in the circadian model organism Synechococcus have revealed that the KaiC protein, the central component of the circadian clock in cyanobacteria, is involved in activation and repression of its own gene transcription. During 24 hours, KaiC hexamers run through different phospho-states during daytime. So far, it has remained unclear which phospho-state of KaiC promotes kaiBC expression and which opposes transcriptional activation. We systematically analyzed various combinations of positive and negative transcriptional feedback regulation by introducing a combined TTFL/PTO model consisting of our previous post-translational oscillator that considers all four phospho-states of KaiC and a transcriptional/translational feedback loop. Only a particular two-loop feedback mechanism out of 32 we have extensively tested is able to reproduce existing experimental observations, including the effects of knockout or overexpression of kai genes. Here, threonine and double phosphorylated KaiC hexamers activate and unphosphorylated KaiC hexamers suppress kaiBC transcription. Our model simulations suggest that the peak expression ratio of the positive and the negative component of kaiBC expression is the main factor for how the different two-loop feedback models respond to removal or to overexpression of kai genes. We discuss parallels between our proposed TTFL/PTO model and two-loop feedback structures found in the mammalian clock. PMID:23516349

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Barnes, Richard; Lehman, Clarence

    2013-06-01

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

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

    PubMed

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

    1988-04-01

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

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

    PubMed Central

    2011-01-01

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

  14. 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…

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

    PubMed

    Ito, Sosuke; Sagawa, Takahiro

    2015-01-01

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

  16. 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.

  17. Molecular Dynamics Simulations of the Cx26 Hemichannel: Insights into Voltage-Dependent Loop-Gating

    PubMed Central

    Kwon, Taekyung; Roux, Benoît; Jo, Sunhwan; Klauda, Jeffery B.; Harris, Andrew L.; Bargiello, Thaddeus A.

    2012-01-01

    Loop-gating is one of two voltage-dependent mechanisms that regulate the open probability of connexin channels. The loop-gate permeability barrier is formed by a segment of the first extracellular loop (E1) (the parahelix) and appears to be accompanied by straightening of the bend angle between E1 and the first transmembrane domain (TM1). Here, all-atom molecular dynamics simulations are used to identify and characterize interacting van der Waals and electrostatic networks that stabilize the parahelices and TM1/E1 bend angles of the open Cx26 hemichannel. Dynamic fluctuations in an electrostatic network in each subunit are directly linked to the stability of parahelix structure and TM1/E1 bend angle in adjacent subunits. The electrostatic network includes charged residues that are pore-lining and thus positioned to be voltage sensors. We propose that the transition to the closed state is initiated by voltage-driven disruption of the networks that stabilize the open-state parahelix configuration, allowing the parahelix to protrude into the channel pore to form the loop-gate barrier. Straightening of the TM1/E1 bend appears to be a consequence of the reorganization of the interacting networks that accompany the conformational change of the parahelix. The electrostatic network extends across subunit boundaries, suggesting a concerted gating mechanism. PMID:22455917

  18. On the self-noise in QASK decision-feedback carrier tracking loops

    NASA Technical Reports Server (NTRS)

    Hinedi, Sami; Lindsey, William C.

    1989-01-01

    Quadrature amplitude-shift keying (QASK) is often used for transmitting two digital data streams in bandwidth-constrained communication systems. Previous analyses of the tracking performance of a decision-feedback carrier tracking loop, which can be used to provide a carrier reference for a QASK signal set, have neglected the effects of the self-noise in the derivation of the loop resonance. The authors incorporate the effects of the self-noise into the analysis of decision-feedback carrier tracking loops. It is demonstrated that failure to account for the self-noise will only result in a conservative assessment of the system's performance, contrary to what might be expected. All results obtained are in closed form and can easily be evaluated numerically for performance prediction purposes.

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

    PubMed

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

    2016-03-16

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

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

    PubMed Central

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

    2015-01-01

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

  1. 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.

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

    NASA Astrophysics Data System (ADS)

    Jones, Lloyd E.; Sandberg, Richard D.

    2011-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Han, Wang; Lin, Tan

    2016-02-01

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

  8. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  10. A technique for sequential segmental neuromuscular stimulation with closed loop feedback control.

    PubMed

    Zonnevijlle, Erik D H; Abadia, Gustavo Perez; Somia, Naveen N; Kon, Moshe; Barker, John H; Koenig, Steven; Ewert, D L; Stremel, Richard W

    2002-01-01

    In dynamic myoplasty, dysfunctional muscle is assisted or replaced with skeletal muscle from a donor site. Electrical stimulation is commonly used to train and animate the skeletal muscle to perform its new task. Due to simultaneous tetanic contractions of the entire myoplasty, muscles are deprived of perfusion and fatigue rapidly, causing long-term problems such as excessive scarring and muscle ischemia. Sequential stimulation contracts part of the muscle while other parts rest, thus significantly improving blood perfusion. However, the muscle still fatigues. In this article, we report a test of the feasibility of using closed-loop control to economize the contractions of the sequentially stimulated myoplasty. A simple stimulation algorithm was developed and tested on a sequentially stimulated neo-sphincter designed from a canine gracilis muscle. Pressure generated in the lumen of the myoplasty neo-sphincter was used as feedback to regulate the stimulation signal via three control parameters, thereby optimizing the performance of the myoplasty. Additionally, we investigated and compared the efficiency of amplitude and frequency modulation techniques. Closed-loop feedback enabled us to maintain target pressures within 10% deviation using amplitude modulation and optimized control parameters (correction frequency = 4 Hz, correction threshold = 4%, and transition time = 0.3 s). The large-scale stimulation/feedback setup was unfit for chronic experimentation, but can be used as a blueprint for a small-scale version to unveil the theoretical benefits of closed-loop control in chronic experimentation. PMID:12028619

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. 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.

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

    PubMed

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

    2012-12-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Yousaf, Saqib; Qin, Shiyin

    2015-12-01

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

  18. 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.

  19. 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.

  20. 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.

  1. Steady-state fluctuations of a genetic feedback loop: An exact solution

    NASA Astrophysics Data System (ADS)

    Grima, R.; Schmidt, D. R.; Newman, T. J.

    2012-07-01

    Genetic feedback loops in cells break detailed balance and involve bimolecular reactions; hence, exact solutions revealing the nature of the stochastic fluctuations in these loops are lacking. We here consider the master equation for a gene regulatory feedback loop: a gene produces protein which then binds to the promoter of the same gene and regulates its expression. The protein degrades in its free and bound forms. This network breaks detailed balance and involves a single bimolecular reaction step. We provide an exact solution of the steady-state master equation for arbitrary values of the parameters, and present simplified solutions for a number of special cases. The full parametric dependence of the analytical non-equilibrium steady-state probability distribution is verified by direct numerical solution of the master equations. For the case where the degradation rate of bound and free protein is the same, our solution is at variance with a previous claim of an exact solution [J. E. M. Hornos, D. Schultz, G. C. P. Innocentini, J. Wang, A. M. Walczak, J. N. Onuchic, and P. G. Wolynes, Phys. Rev. E 72, 051907 (2005), 10.1103/PhysRevE.72.051907, and subsequent studies]. We show explicitly that this is due to an unphysical formulation of the underlying master equation in those studies.

  2. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  4. 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.

  5. 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.

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

    PubMed Central

    Harrison, Mary E.; Dunlop, Mary J.

    2012-01-01

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

  7. 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.

  8. 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

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

    PubMed Central

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

    2014-01-01

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

  10. Reliable Control Using Disturbance Observer and Equivalent Transfer Function for Position Servo System in Current Feedback Loop Failure

    NASA Astrophysics Data System (ADS)

    Ishikawa, Kaoru; Nakamura, Taro; Osumi, Hisashi

    A reliable control method is proposed for multiple loop control system. After a feedback loop failure, such as case of the sensor break down, the control system becomes unstable and has a big fluctuation even if it has a disturbance observer. To cope with this problem, the proposed method uses an equivalent transfer function (ETF) as active redundancy compensation after the loop failure. The ETF is designed so that it does not change the transfer function of the whole system before and after the loop failure. In this paper, the characteristic of reliable control system that uses an ETF and a disturbance observer is examined by the experiment that uses the DC servo motor for the current feedback loop failure in the position servo system.

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

    PubMed

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

    2015-11-12

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

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

    NASA Astrophysics Data System (ADS)

    Narula, Jatin; Igoshin, Oleg

    2011-03-01

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

  13. 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.

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

    NASA Astrophysics Data System (ADS)

    Hanai, Yuji; Hayashi, Yasuhiro; Matsuki, Junya

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

  15. Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments

    PubMed Central

    Busse, Dorothea; de la Rosa, Maurus; Hobiger, Kirstin; Thurley, Kevin; Flossdorf, Michael; Scheffold, Alexander; Höfer, Thomas

    2010-01-01

    Cytokines are pleiotropic and readily diffusible messenger molecules, raising the question of how their action can be confined to specific target cells. The T cell cytokine interleukin-2 (IL-2) is essential for the homeostasis of regulatory T (Treg) cells that suppress (auto)immunity and stimulates immune responses mediated by conventional T cells. We combined mathematical modeling and experiments to dissect the dynamics of the IL-2 signaling network that links the prototypical IL-2 producers, conventional T helper (Th) cells, and Treg cells. We show how the IL-2-induced upregulation of high-affinity IL-2 receptors (IL-2R) establishes a positive feedback loop of IL-2 signaling. This feedback mediates a digital switch for the proliferation of Th cells and functions as an analog amplifier for the IL-2 uptake capacity of Treg cells. Unlike other positive feedbacks in cell signaling that augment signal propagation, the IL-2/IL-2R loop enhances the capture of the signal molecule and its degradation. Thus Treg and Th cells can compete for IL-2 and restrict its range of action through efficient cellular uptake. Depending on activation status and spatial localization of the cells, IL-2 may be consumed exclusively by Treg or Th cells, or be shared between them. In particular, a Treg cell can deprive a stimulated Th cell of its IL-2, but only when the cells are located in close proximity, within a few tens of micrometers. The present findings explain how IL-2 can play two disctinct roles in immune regulation and point to a hitherto largely unexplored spatiotemporal complexity of cytokine signaling. PMID:20133667

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

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

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

    2010-01-01

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

  18. Implementation on a desktop computer of the real time feedback control loop of a scanning probe microscope

    NASA Astrophysics Data System (ADS)

    Aloisi, G.; Bacci, F.; Carlà, M.; Dolci, D.; Lanzi, L.

    2008-11-01

    A software package has been developed to implement the real time feedback control loop needed in scanning probe microscopy on a general purpose desktop computer of the current high-speed/multicore generation. The main features of the implementation of both the feedback loop and the control of the experiment on the same computer are discussed. The package can work with several general purpose data acquisition boards and can be extended in a modular way to further board models; timing performance has been tested with several hardware configurations and some applications common in scanning probe microscopy. The package is available under an Open Source license.

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

    NASA Astrophysics Data System (ADS)

    Krishna, Sandeep

    2008-03-01

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

  20. 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.

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

    PubMed

    Vuong, Bao Q; Herrick-Reynolds, Kayleigh; Vaidyanathan, Bharat; Pucella, Joseph N; Ucher, Anna J; Donghia, Nina M; Gu, Xiwen; Nicolas, Laura; Nowak, Urszula; Rahman, Numa; Strout, Matthew P; Mills, Kevin D; Stavnezer, Janet; Chaudhuri, Jayanta

    2013-11-01

    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

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

    PubMed Central

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

    2012-01-01

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

  3. 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

  4. Performance of the load-in-the-loop single Op-Amp voltage Controlled current source from the Op-Amp Parameters

    NASA Astrophysics Data System (ADS)

    Macías, R.; Seoane, F.; Bragós, R.

    2010-04-01

    In recent years, Electrical Bioimpedance (EBI) methods have gained importance. These methods are often based on obtaining impedance spectrum in the range of β-dispersion, i.e. from a few kHz up to some MHz. To measure EBI a constant current is often injected and the voltage across the tissue under study is recorded. Due to the performance of the current source influences the performance of the entire system, in terms of frequency range, several designs have been implemented and studied. In this paper the basic structure of a Voltage-Controlled Current Source based on a single Op-Amp in inverter configuration with a floating load, known as load-in-the-loop current source, is revisited and studied deeply. We focus on the dependence of the output impedance with the circuit parameters, i.e. the feedback resistor and the inverter-input resistor, and the Op-Amp main parameters, i.e. open loop gain, CMRR and input impedance. After obtaining the experimental results, using modern Op-Amps, and comparing to the theoretical and simulated ones, they confirm the design under study can be a good solution for multi-frequency wideband EBI applications because of higher values of the output impedance than 100kΩ at 1MHz are obtained. Furthermore, an enhancement of the basic design, using a current conveyor as a first stage, is proposed, studied and implemented.

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

    PubMed Central

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

    2016-01-01

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

  6. 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.

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2010-11-01

    the existence of an intense feedback-loop control of the pathway by the activated ERK that maybe responsible for the damped oscillations we saw in the fraction of activated MEK both in the experiments and simulations. In addition, the model analysis suggested that phosphorylation/deactivation of RKIP during the transient stimulation may have a significant effect on the signalling peaks of both MEK and ERK. This later result suggests that dynamic modulation of signal inhibitors during stimulation may be a regulatory mechanism in ERK signalling and other pathways. PMID:20717620

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

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  10. Speciation as a positive feedback loop between postzygotic and prezygotic barriers to gene flow.

    PubMed Central

    Servedio, Maria R; Saetre, Glenn-Peter

    2003-01-01

    Speciation is intimately associated with the evolution of sex-and-reproduction-related traits, including those affecting hybrid incompatibility (postzygotic isolation) and species recognition (prezygotic isolation). Genes controlling such traits are not randomly distributed in the genome but are particularly abundant on the sex chromosomes. However, the evolutionary consequences of the sex linkage of genes involved in speciation have been little explored. Here, we present simulations of a continent-island diploid model that examines the effects of reduced recombination using both autosomal and sex-linked inheritance. We show first that linkage between genes affecting postzygotic and prezygotic isolation leads to a positive feedback loop in which both are strengthened. As species recognition evolves, genes causing hybrid incompatibility will hitchhike along with those improving premating isolation, leading to stronger hybrid incompatibility and thus increased pressure for further preference divergence. Second, we show that this loop effect is generally enhanced by sex linkage, because recombination is eliminated in the heterogametic sex, leading to tighter effective linkage between the two classes of genes and because natural selection is more efficient at sex-linked loci, as recessive alleles are not masked by dominance in the heterogametic sex. Accordingly, hitchhiking can be important in promoting speciation and can also lead to increased postzygotic isolation through adaptive evolution. PMID:12965012

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2013-03-28

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

  13. 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

  14. 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.

  15. MicroRNAs Constitute a Negative Feedback Loop in Streptococcus pneumoniae-Induced Macrophage Activation.

    PubMed

    Griss, Kathrin; Bertrams, Wilhelm; Sittka-Stark, Alexandra; Seidel, Kerstin; Stielow, Christina; Hippenstiel, Stefan; Suttorp, Norbert; Eberhardt, Martin; Wilhelm, Jochen; Vera, Julio; Schmeck, Bernd

    2016-07-15

    Streptococcus pneumoniae causes high mortality as a major pneumonia-inducing pathogen. In pneumonia, control of innate immunity is necessary to prevent organ damage. We assessed the role of microRNAs (miRNAs) as regulators in pneumococcal infection of human macrophages. Exposure of primary blood-derived human macrophages with pneumococci resulted in transcriptional changes in several gene clusters and a significant deregulation of 10 microRNAs. Computational network analysis retrieved miRNA-146a as one putatively important regulator of pneumococci-induced host cell activation. Its induction depended on bacterial structural integrity and was completely inhibited by blocking Toll-like receptor 2 (TLR-2) or depleting its mediator MyD88. Furthermore, induction of miRNA-146a release did not require the autocrine feedback of interleukin 1β and tumor necrosis factor α released from infected macrophages, and it repressed the TLR-2 downstream mediators IRAK-1 and TRAF-6, as well as the inflammatory factors cyclooxygenase 2 and interleukin 1β. In summary, pneumococci recognition induces a negative feedback loop, preventing excessive inflammation via miR-146a and potentially other miRNAs. PMID:26984146

  16. 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

  17. 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

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

    NASA Astrophysics Data System (ADS)

    Soprano, C.

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

  19. 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)

  20. 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.

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

    PubMed

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

    2015-03-15

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

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

    NASA Astrophysics Data System (ADS)

    Yingping, Chen; Zhiqian, Li

    2015-05-01

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

  3. Analysis of a dc SQUID readout scheme with voltage feedback circuit and low-noise preamplifier

    NASA Astrophysics Data System (ADS)

    Zeng, Jia; Zhang, Yi; Schmelz, Matthias; Mück, Michael; Krause, Hans-Joachim; Braginski, Alex I.; Lee, Yong-Ho; Stolz, Ronny; Kong, Xiangyan; Xie, Xiaoming; Meyer, Hans-Georg; Offenhäusser, Andreas; Jiang, Mianheng

    2014-08-01

    We analyzed the dc SQUID with voltage feedback circuit (VFC) and a low-noise room-temperature preamplifier to evaluate the feasibility of a low-noise SQUID direct-coupled readout scheme (DRS), possibly eliminating the need for a two-stage scheme employing a SQUID preamplifier. The passive VFC, connected in parallel to the SQUID, consists of a resistor Rs in series with an inductor L s. This inductor is coupled to the SQUID by a mutual inductance Ms. The purpose of the VFC is to increase the SQUID’s flux-to-voltage transfer coefficient ∂V/∂Φ, thus reducing the preamplifier noise contribution δΦpreamp. However, at the same time, VFC introduces the thermal noise of Rs, δΦR, which may not be negligible. Generally, the noise of the readout scheme, δΦreadout, may thus include both δΦpreamp and δΦR, i.e., δΦreadout2 = δΦpreamp2 + δΦR2. To characterize the SQUID operation with VFC we introduced two dimensionless parameters, r = Rs/Rd and Δ = (M s/Mdyn) - (Rs/R d), where Rd and Mdyn = 1/(∂i/∂Φ) are dynamic properties of the SQUID itself. For assumed intrinsic SQUID parameters, we then numerically analyzed the dependence of δΦreadout noise components on r and Δ to determine their suitable ranges and the minimum of δΦreadout. To verify our analysis, we experimentally characterized, in liquid helium, three niobium SQUIDs with VFC, having suitably chosen r and Δ. The measured SQUID system flux noise was on the order of 1 μΦ0/√Hz, comparable to the intrinsic noise of the SQUID itself. The deduced equivalent voltage noise was comparable to that of a SQUID preamplifier in the two-stage readout. Simple single-stage ultra-low-noise SQUID DRS readout was thus demonstrated.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2011-12-15

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

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

    PubMed Central

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

    2015-01-01

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

  8. PPARgamma ligands suppress the feedback loop between E2F2 and cyclin-E1.

    PubMed

    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

    PPARgamma is a nuclear hormone receptor that plays a key role in the induction of peroxisome proliferation. A number of studies showed that PPARgamma ligands suppress cell cycle progression; however, the mechanism remains to be determined. Here, we showed that PPARgamma 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. PMID:18355447

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

    PubMed

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

    2016-03-01

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

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

    SciTech Connect

    Iizuka, Katsumi; Horikawa, Yukio

    2008-09-12

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

  11. A feedback loop between Wolbachia and the Drosophila gurken mRNP complex influences Wolbachia titer

    PubMed Central

    Serbus, Laura R.; Ferreccio, Amy; Zhukova, Mariya; McMorris, Chanel L.; Kiseleva, Elena; Sullivan, William

    2011-01-01

    Although much is known about interactions between bacterial endosymbionts and their hosts, little is known concerning the host factors that influence endosymbiont titer. Wolbachia endosymbionts are globally dispersed throughout most insect species and are the causative agent in filarial nematode-mediated disease. Our investigation indicates that gurken (grk), a host gene encoding a crucial axis determinant, has a cumulative, dosage-sensitive impact on Wolbachia growth and proliferation during Drosophila oogenesis. This effect appears to be mediated by grk mRNA and its protein-binding partners Squid and Hrp48/Hrb27C, implicating the grk mRNA–protein (mRNP) complex as a rate-limiting host factor controlling Wolbachia titer. Furthermore, highly infected flies exhibit defects that match those occurring with disruption of grk mRNPs, such as nurse cell chromatin disruptions and malformation of chorionic appendages. These findings suggest a feedback loop in which Wolbachia interaction with the grk mRNP affects both Wolbachia titer and grk mRNP function. PMID:22193955

  12. Positive feedback loop between cancer stem cells and angiogenesis in hepatocellular carcinoma.

    PubMed

    Yao, Hong; Liu, Nianli; Lin, Marie C; Zheng, Junnian

    2016-09-01

    Anti-angiogenesis-related therapies have become the standard care for patients with advanced hepatocellular carcinoma (HCC), as HCC is a highly vascularized solid tumor. Unfortunately, only modest and limited efficacies are observed. Emerging evidence have attributed to the limited efficacy to the presence of cancer stem cells (CSCs) in the tumor. CSCs predominantly drives angiogenesis via releasing proangiogenic factors and exosomes. They have the ability to resistant intratumoral hypoxia via autophagy or by directly forming the tubular structure to obtain blood. On the other hand, the vascular niche in tumor microenvironment also releases growth factors via juxtacrine and paracrine mechanisms to support the growth of CSCs and maintain its stemness features. This positive feedback loop between angiogenesis and CSCs exists in liver tumor microenvironment that is responsible for the development and poor prognosis of HCC. In this review, we summarize recent advances in our understanding of the crosstalks between angiogenesis and CSCs, and their interactions in liver tumor microenvironment and their purpose that an effective anti-angiogenic therapy should also target CSCs for HCC treatment. PMID:27108065

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

    PubMed

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

    2013-03-01

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

  14. 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.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Non-hypoxic activation of the negative regulatory feedback loop of prolyl-hydroxylase oxygen sensors.

    PubMed

    Tug, Suzan; Delos Reyes, Buena; Fandrey, Joachim; Berchner-Pfannschmidt, Utta

    2009-07-10

    Hypoxia inducible factors (HIF) coordinate cellular responses towards hypoxia. HIFs are mainly regulated by a group of prolyl-hydroxylases (PHDs) that in the presence of oxygen, target the HIFalpha subunit for degradation. Herein, we studied the role of nitric oxide (NO) in regulating PHD activities under normoxic conditions. In the present study we show that different NO-donors initially inhibited endogenous PHD2 activity which led to accumulation of HIF-1alpha subsequently to enhance HIF-1 dependent increased PHD2 promoter activity. Consequently PHD2 abundance and activity were strongly induced which caused downregulation of HIF-1alpha. Interestingly, upregulation of endogenous PHD2 activity by NO was not found in cells that lack an intact pVHL dependent degradation pathway. Recovery of PHD activity required intact cells and was not observed in cell extracts or recombinant PHD2. In conclusion induction of endogenous PHD2 activity by NO is dependent on a feedback loop initiated despite normoxic conditions. PMID:19427832

  19. A negative feedback loop at the nuclear periphery regulates GAL gene expression

    PubMed Central

    Green, Erin M.; Jiang, Ying; Joyner, Ryan; Weis, Karsten

    2012-01-01

    The genome is nonrandomly organized within the nucleus, but it remains unclear how gene position affects gene expression. Silenced genes have frequently been found associated with the nuclear periphery, and the environment at the periphery is believed to be refractory to transcriptional activation. However, in budding yeast, several highly regulated classes of genes, including the GAL7-10-1 gene cluster, are known to translocate to the nuclear periphery concurrent with their activation. To investigate the role of gene positioning on GAL gene expression, we monitored the effects of mutations that disrupt the interaction between the GAL locus and the periphery or synthetically tethered the locus to the periphery. Localization to the nuclear periphery was found to dampen initial GAL gene induction and was required for rapid repression after gene inactivation, revealing a function for the nuclear periphery in repressing endogenous GAL gene expression. Our results do not support a gene-gating model in which GAL gene interaction with the nuclear pore ensures rapid gene expression, but instead they suggest that a repressive environment at the nuclear periphery establishes a negative feedback loop that enables the GAL locus to respond rapidly to changes in environmental conditions. PMID:22323286

  20. 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

  1. A Novel Network Integrating a miRNA-203/SNAI1 Feedback Loop which Regulates Epithelial to Mesenchymal Transition

    PubMed Central

    Moes, Michèle; Le Béchec, Antony; Crespo, Isaac; Laurini, Christina; Halavatyi, Aliaksandr; Vetter, Guillaume; del Sol, Antonio; Friederich, Evelyne

    2012-01-01

    Background The majority of human cancer deaths are caused by metastasis. The metastatic dissemination is initiated by the breakdown of epithelial cell homeostasis. During this phenomenon, referred to as epithelial to mesenchymal transition (EMT), cells change their genetic and trancriptomic program leading to phenotypic and functional alterations. The challenge of understanding this dynamic process resides in unraveling regulatory networks involving master transcription factors (e.g. SNAI1/2, ZEB1/2 and TWIST1) and microRNAs. Here we investigated microRNAs regulated by SNAI1 and their potential role in the regulatory networks underlying epithelial plasticity. Results By a large-scale analysis on epithelial plasticity, we highlighted miR-203 and its molecular link with SNAI1 and the miR-200 family, key regulators of epithelial homeostasis. During SNAI1-induced EMT in MCF7 breast cancer cells, miR-203 and miR-200 family members were repressed in a timely correlated manner. Importantly, miR-203 repressed endogenous SNAI1, forming a double negative miR203/SNAI1 feedback loop. We integrated this novel miR203/SNAI1 with the known miR200/ZEB feedback loops to construct an a priori EMT core network. Dynamic simulations revealed stable epithelial and mesenchymal states, and underscored the crucial role of the miR203/SNAI1 feedback loop in state transitions underlying epithelial plasticity. Conclusion By combining computational biology and experimental approaches, we propose a novel EMT core network integrating two fundamental negative feedback loops, miR203/SNAI1 and miR200/ZEB. Altogether our analysis implies that this novel EMT core network could function as a switch controlling epithelial cell plasticity during differentiation and cancer progression. PMID:22514743

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

    NASA Astrophysics Data System (ADS)

    Huebert, B. J.

    2004-12-01

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

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

    PubMed

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

    2012-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Shen, B.-W.

    2014-04-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    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. PMID:24494193

  8. ADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis

    PubMed Central

    Lai, Yongjie; Bai, Xiaohui; Zhao, Yunpeng; Tian, Qingyun; Liu, Ben; Lin, Edward A.; Chen, Yuqing; Lee, Brendan; Appleton, C Thomas G.; Beier, Frank; Yu, Xiu-Ping; Liu, Chuan-ju

    2015-01-01

    Objective To examine the expression of ADAMTS-7 during the progression of osteoarthritis (OA), defining its role in the pathogenesis of OA, and elucidating the molecular events involved. Methods ADAMTS-7 expression in cartilage of a rat OA model was assayed using immunohistochemistry. Cartilage-specific ADAMTS-7 transgenic mice and ADAMTS-7 small interfering (si)RNA knockdown mice were generated and used to analyse OA progression in both spontaneous and surgically induced OA models. Cartilage degradation and OA was evaluated using Safranin-O staining, immunohistochemistry, ELISA and western blotting. In addition, mRNA expression of tumour necrosis factor (TNF)-α and metalloproteinases known to be involved in cartilage degeneration in OA was analysed. Furthermore, the transactivation of ADAMTS-7 by TNF-α and its downstream NF-κB signalling was measured using reporter gene assay. Results ADAMTS-7 expression was elevated during disease progression in the surgically induced rat OA model. Targeted overexpression of ADAMTS-7 in chondrocytes led to chondrodysplasia characterised by short-limbed dwarfism and a delay in endochondral ossification in ‘young mice’ and a spontaneous OA-like phenotype in ‘aged’ mice. In addition, overexpression of ADAMTS-7 led to exaggerated breakdown of cartilage and accelerated OA progression, while knockdown of ADAMTS-7 attenuated degradation of cartilage matrix and protected against OA development, in surgically induced OA models. ADAMTS-7 upregulated TNF-α and metalloproteinases associated with OA; in addition, TNF-α induced ADAMTS-7 through NF-κB signalling. Conclusions ADAMTS-7 and TNF-α form a positive feedback loop in the regulation of cartilage degradation and OA progression, making them potential molecular targets for prevention and treatment of joint degenerative diseases, including OA. PMID:23928557

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

    PubMed Central

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

    2012-01-01

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

  10. 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.

  11. ASDTIC - A feedback control innovation.

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

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

    PubMed

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

    2016-05-01

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

  13. 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.

  14. 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. PMID:27037372

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

    PubMed

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

    2014-03-28

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

  16. Loop Analysis of Causal Feedback in Epidemiology: An Illustration Relating To Urban Neighborhoods and Resident Depressive Experiences

    PubMed Central

    2008-01-01

    The causal feedback implied by urban neighborhood conditions that shape human health experiences, that in turn shape neighborhood conditions through a complex causal web, raises a challenge for traditional epidemiological causal analyses. This article introduces the loop analysis method, and builds off of a core loop model linking neighborhood property vacancy rate, resident depressive symptoms, rate of neighborhood death, and rate of neighborhood exit in a feedback network. I justify and apply loop analysis to the specific example of depressive symptoms and abandoned urban residential property to show how inquiries into the behavior of causal systems can answer different kinds of hypotheses, and thereby compliment those of causal modeling using statistical models. Neighborhood physical conditions that are only indirectly influenced by depressive symptoms may nevertheless manifest in the mental health experiences of their residents; conversely, neighborhood physical conditions may be a significant mental health risk for the population of neighborhood residents. I find that participatory greenspace programs are likely to produce adaptive responses in depressive symptoms and different neighborhood conditions, which are different in character to non-participatory greenspace interventions. PMID:17706851

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

    PubMed

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

    2015-12-18

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

  18. A short report on voltage-to-frequency conversion for HISTRAP RF system tuning control loops

    SciTech Connect

    Hasanul Basher, A.M.

    1991-09-01

    One of the requirements of the HISTRAP RF accelerating system is that the frequency of the accelerating voltage for the cavity must keep in step with the change in the magnetic field. As the energy of the particle increases, the magnetic field is increased to keep the radius of the particle orbit constant. At the same time, the frequency of the electric field must be changed to insure that it is synchronized with the angular movement of the particle. So we need to generate the frequency of the accelerating voltage in relation to the magnetic field. The frequency generation can be accomplished in two stages. The first stage of frequency generation consists of measuring the magnetic field in terms of voltage which is already developed. The second stage is to convert this voltage into frequency. Final frequency precision can be achieved by deriving a frequency-correcting signal from the beam position. This project is concerned with generating the frequency from the analog voltage. The speed of response required will place very stringent requirements on both hardware and software. Technology is available to carry out this task. A hardware configuration has been established and software has been developed. In the following section, we describe the implementation strategy, the hardware configuration, and the desired specifications. Next, we present the software developed, results obtained, along with capabilities and limitations of the system. Finally, we suggest alternate solutions to overcome some of the limitations toward meeting our goal. In the appendices, we include program listings.

  19. REVEILLE8 and PSEUDO-REPONSE REGULATOR5 Form a Negative Feedback Loop within the Arabidopsis Circadian Clock

    PubMed Central

    Rawat, Reetika; Jones, Matthew A.; Schwartz, Jacob; Salemi, Michelle R.; Phinney, Brett S.; Harmer, Stacey L.

    2011-01-01

    Circadian rhythms provide organisms with an adaptive advantage, allowing them to regulate physiological and developmental events so that they occur at the most appropriate time of day. In plants, as in other eukaryotes, multiple transcriptional feedback loops are central to clock function. In one such feedback loop, the Myb-like transcription factors CCA1 and LHY directly repress expression of the pseudoresponse regulator TOC1 by binding to an evening element (EE) in the TOC1 promoter. Another key regulatory circuit involves CCA1 and LHY and the TOC1 homologs PRR5, PRR7, and PRR9. Purification of EE–binding proteins from plant extracts followed by mass spectrometry led to the identification of RVE8, a homolog of CCA1 and LHY. Similar to these well-known clock genes, expression of RVE8 is circadian-regulated with a dawn phase of expression, and RVE8 binds specifically to the EE. However, whereas cca1 and lhy mutants have short period phenotypes and overexpression of either gene causes arrhythmia, rve8 mutants have long-period and RVE8-OX plants have short-period phenotypes. Light input to the clock is normal in rve8, but temperature compensation (a hallmark of circadian rhythms) is perturbed. RVE8 binds to the promoters of both TOC1 and PRR5 in the subjective afternoon, but surprisingly only PRR5 expression is perturbed by overexpression of RVE8. Together, our data indicate that RVE8 promotes expression of a subset of EE–containing clock genes towards the end of the subjective day and forms a negative feedback loop with PRR5. Thus RVE8 and its homologs CCA1 and LHY function close to the circadian oscillator but act via distinct molecular mechanisms. PMID:21483796

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

    PubMed

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

    2013-10-15

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

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

    PubMed Central

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

    2016-01-01

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

  2. Examining the feedback signals used in closed-loop control of intense laser fragmentation of CO{sup +}

    SciTech Connect

    Wells, E.; Todt, Michael; Jochim, Bethany; Gregerson, Neal; Averin, R.; Wells, Nathan G.; Smolnisky, N. L.; Jastram, Nathan; McKenna, J.; Sayler, A. M.; Johnson, Nora G.; Zohrabi, M.; Gaire, B.; Carnes, K. D.; Ben-Itzhak, I.

    2009-12-15

    A closed-loop feedback system is used to determine the optimal pulse shapes for manipulating the branching ratio of carbon monoxide following ionization by an intense laser pulse. We focus on manipulating the C{sup +}+O and C+O{sup +} branching ratios of excited states of transient CO{sup +}. The feedback control system consists of a high resolution time-of-flight spectrometer coupled via a genetic feedback algorithm to an acousto-optical programmable dispersive filter that is incorporated into the ultrafast laser system. Using the spectrometer resolution to distinguish dissociation pathways and select a specific pathway to drive the algorithm, we are able to demonstrate enhanced control of some fragmentation channels. Principal control analysis indicates that the more specific feedback results in numerically simpler optimal pulse shapes. The combination of a more specific target and reduction in pulse complexity could lead to more straightforward investigations of the control mechanism. Analysis of the pulse shapes in conjunction with measurement of the fragment kinetic energy release distributions obtained from the optimized laser pulses is used to probe the dissociative ionization mechanisms.

  3. 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.

  4. Voltage-Biased Superconducting Transition-Edge Bolometer with Strong Electrothermal Feedback Operated at 370 mK.

    PubMed

    Lee, S F; Gildemeister, J M; Holmes, W; Lee, A T; Richards, P L

    1998-06-01

    We present an experimental study of a composite voltage-biased superconducting bolometer (VSB). The tested VSB consists of a Ti-film superconducting thermometer (T(c) ~375 mK) on a Si substrate suspended by NbTi superconducting leads. A resistor attached to the substrate provides calibrated heat input into the bolometer. The current through the bolometer is measured with a superconducting quantum interference device ammeter. Strong negative electrothermal feedback fixes the bolometer temperature at T(c) and reduces the measured response time from 2.6 s to 13 ms. As predicted, the measured current responsivity of the bolometer is equal to the inverse of the bias voltage. A noise equivalent power of 5 x 10(-17) W/ radicalHz was measured for a thermal conductance G ~ 4.7 x 10(-10) W/K, which is consistent with the expected thermal noise. Excess noise was observed for bias conditions for which the electrothermal feedback strength was close to maximum. PMID:18273298

  5. 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.

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2015-12-01

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

  12. 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.

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

    PubMed

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

    2015-01-01

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

  14. Complete low power controller for high voltage power systems

    SciTech Connect

    Sumner, R.; Blanar, G.

    1997-12-31

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    1983-10-01

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

  17. 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.

  18. 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

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

    PubMed

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

    2015-03-15

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

  20. 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

    2015-08-01

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

  1. 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.

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

    SciTech Connect

    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.

  3. 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…

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

    PubMed Central

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

    2016-01-01

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

  5. 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.

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

    NASA Astrophysics Data System (ADS)

    Burkholder, Michael B.; Litster, Shawn

    2015-02-01

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

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

    PubMed

    Hou, Li-Kun; Yu, Yue; Xie, Ye-Gong; Wang, Jie; Mao, Jie-Fei; Zhang, Bin; Wang, Xin; Cao, Xu-Chen

    2016-05-01

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

  8. 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

  9. A Runx2/miR-3960/miR-2861 regulatory feedback loop during mouse osteoblast differentiation.

    PubMed

    Hu, Rong; Liu, Wei; Li, Hui; Yang, Li; Chen, Chao; Xia, Zhu-Ying; Guo, Li-Juan; Xie, Hui; Zhou, Hou-De; Wu, Xian-Ping; Luo, Xiang-Hang

    2011-04-01

    Our recent study showed that miR-2861 promotes osteoblast differentiation by targeting histone deacetylase 5, resulting in increased runt-related transcription factor 2 (Runx2) protein production. Here we identified another new microRNA (miRNA) (miR-3960) that played a regulatory role in osteoblast differentiation through a regulatory feedback loop with miR-2861. miR-3960 and miR-2861 were found clustered at the same loci. miR-3960 was transcribed during bone morphogenic protein 2 (BMP2)-induced osteogenesis of ST2 stromal cells. Overexpression of miR-3960 promoted BMP2-induced osteoblastogenesis. However, the inhibition of miR-3960 expression attenuated the osteoblastogenesis. Homeobox A2 (Hoxa2), a repressor of Runx2 expression, was confirmed to be a target of miR-3960. Electrophoretic mobility shift assay and chromatin immunoprecipitation experiments confirmed that Runx2 bound to the promoter of the miR-3960/miR-2861 cluster. Furthermore, overexpression of Runx2 induced miR-3960/miR-2861 transcription, and block of Runx2 expression attenuated BMP2-induced miR-3960/miR-2861 transcription. Here we report that miR-3960 and miR-2861, transcribed together from the same miRNA polycistron, both function in osteoblast differentiation through a novel Runx2/miR-3960/miR-2861 regulatory feedback loop. Our findings provide new insights into the roles of miRNAs in osteoblast differentiation. PMID:21324897

  10. 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

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

    PubMed

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

    2000-07-28

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

  12. 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

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

    PubMed

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

    2015-12-01

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

  14. 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.

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

    PubMed Central

    Selitrennik, Michael; Lev, Sima

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-16

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

  18. Viral Nucleases Induce an mRNA Degradation-Transcription Feedback Loop in Mammalian Cells.

    PubMed

    Abernathy, Emma; Gilbertson, Sarah; Alla, Ravi; Glaunsinger, Britt

    2015-08-12

    Gamma-herpesviruses encode a cytoplasmic mRNA-targeting endonuclease, SOX, that cleaves most cellular mRNAs. Cleaved fragments are subsequently degraded by the cellular 5'-3' mRNA exonuclease Xrn1, thereby suppressing cellular gene expression and facilitating viral evasion of host defenses. We reveal that mammalian cells respond to this widespread cytoplasmic mRNA decay by altering RNA Polymerase II (RNAPII) transcription in the nucleus. Measuring RNAPII recruitment to promoters and nascent mRNA synthesis revealed that the majority of affected genes are transcriptionally repressed in SOX-expressing cells. The transcriptional feedback does not occur in response to the initial viral endonuclease-induced cleavage, but instead to degradation of the cleaved fragments by cellular exonucleases. In particular, Xrn1 catalytic activity is required for transcriptional repression. Notably, viral mRNA transcription escapes decay-induced repression, and this escape requires Xrn1. Collectively, these results indicate that mRNA decay rates impact transcription and that gamma-herpesviruses use this feedback mechanism to facilitate viral gene expression. PMID:26211836

  19. THE VOLTAGE DEPENDENCE OF GATING CURRENTS OF THE NEURONAL CAV3.3 CHANNEL IS DETERMINED BY THE GATING BRAKE IN THE I-II LOOP

    PubMed Central

    Karmažínová, Mária; Baumgart, Joel; Perez-Reyes, Edward; Lacinová, L'ubica

    2012-01-01

    Low-voltage activated CaV3 Ca2+ channels have an activation threshold around −60 mV, which is lower than the activation threshold of other voltage-dependent calcium channels (VDCC). The kinetics of their activation at membrane voltages just above the activation threshold is much slower than the activation kinetics of other VDCCs. It was demonstrated recently that the intracellular loop connecting repeats I and II of all three CaV3 channels contains a so-called “gating brake.” Disruption of this brake yields channels that activate at even more hyperpolarized potentials with significantly accelerated kinetics. We have compared gating of a wild type CaV3.3 channel and a mutated ID12 channel, in which the putative gating brake at the proximal part of the I-II loop was removed. Voltage dependence of the gating current activation was shifted by 34.6 mV towards more hyperpolarized potentials in ID12 channel. Kinetics of the on-charge activation was significantly accelerated, while kinetics of the off-charge was not altered. We conclude that the putative gating brake in I-II loop hinders not only the opening of the conducting pore but also the activating movement of voltage sensing S4 segments, stabilizing the channel in its closed state. PMID:21340458

  20. Generation of a periodic sequence of powerful ultrashort pulses in a traveling wave tube with bleachable absorber in the feedback loop

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

    It is shown that a periodic series of ultrashort pulses can be formed in electron microwave generators with a bleachable absorber in the feedback loop. The peak power of such radiation is considerably higher than radiation power in stationary modes. The pulsed generation method is analogous to the method of passive synchronization of waves, which is widely used in laser physics.

  1. 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.

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

    PubMed

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

    2016-02-22

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

  3. 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.

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

    NASA Technical Reports Server (NTRS)

    Bearden, Douglas B. (Inventor)

    2007-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Bearden, Douglas B. (Inventor)

    2007-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Chapin, W. G.

    1974-01-01

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

  7. Acidic amino acids in the first intracellular loop contribute to voltage- and calcium- dependent gating of anoctamin1/TMEM16A.

    PubMed

    Xiao, Qinghuan; Cui, Yuanyuan

    2014-01-01

    Anoctamin1 (Ano1, or TMEM16A) is a Ca2+-activated chloride channel that is gated by both voltage and Ca2+. We have previously identified that the first intracellular loop that contains a high density of acidic residues mediates voltage- and calcium-dependent gating of Ano1. Mutation of the four consecutive glutamates (444EEEE447) inhibits the voltage-dependent activation of Ano1, whereas deletion of these residues decreases apparent Ca2+ sensitivity. In the present study, we further found that deletion of 444EEEEEAVKD452 produced a more than 40-fold decrease in the apparent Ca2+ sensitivity with altered activation kinetics. We then systematically mutated each acidic residue into alanine, and analyzed the voltage- and calcium dependent activation of each mutation. Activation kinetics of wild type Ano1 consisted of a fast component (τfast) that represented voltage-dependent mode, and a slow component (τslow) that reflected the Ca2+-dependent modal gating. E444A, E445A, E446A, E447A, E448A, and E457A mutations showed a decrease in the τfast, significantly inhibited voltage-dependent activation of Ano1 in the absence of Ca2+, and greatly shifted the G-V curve to the right, suggesting that these glutamates are involved in voltage-gating of Ano1. Furthermore, D452A, E464A, E470A, and E475A mutations that did not alter voltage-dependent activation of the channel, significantly decreased Ca2+ dependence of G-V curve, exhibited an increase in the τslow, and produced a 2-3 fold decrease in the apparent Ca2+ sensitivity, suggesting that these acidic residues are involved in Ca2+-dependent gating of the channel. Our data show that acidic residues in the first intracellular loop are the important structural determinant that couples the voltage and calcium dependent gating of Ano1. PMID:24901998

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

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed Central

    Bleris, Leonidas; Ma, Lan

    2015-01-01

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

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

    PubMed

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

    2016-01-15

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

  11. 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

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

    PubMed Central

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

    2012-01-01

    The reversibly red (R)/far-red (FR)-light-responsive phytochrome (phy) photosensory system initiates both the deetiolation process in dark-germinated seedlings upon first exposure to light, and the shade-avoidance process in fully deetiolated seedlings upon exposure to vegetational shade. The intracellular signaling pathway from the light-activated photoreceptor conformer (Pfr) to the transcriptional network that drives these responses involves direct, physical interaction of Pfr with a small subfamily of bHLH transcription factors, termed Phy-Interacting Factors (PIFs), which induces rapid PIF proteolytic degradation. In addition, there is evidence of further complexity in light-grown seedlings, whereby phyB–PIF interaction reciprocally induces phyB degradation, in a mutually-negative, feedback-loop configuration. Here, to assess the relative contributions of these antagonistic activities to the net phenotypic readout in light-grown seedlings, we have examined the magnitude of the light- and simulated-shade-induced responses of a pentuple phyBpif1pif3pif4pif5 (phyBpifq) mutant and various multiple pif-mutant combinations. The data (1) reaffirm that phyB is the predominant, if not exclusive, photoreceptor imposing the inhibition of hypocotyl elongation in deetiolating seedlings in response to prolonged continuous R irradiation and (2) show that the PIF quartet (PIF1, PIF3, PIF4, and PIF5) retain and exert a dual capacity to modulate hypocotyl elongation under these conditions, by concomitantly promoting cell elongation through intrinsic transcriptional-regulatory activity, and reducing phyB-inhibitory capacity through feedback-loop-induced phyB degradation. In shade-exposed seedlings, immunoblot analysis shows that the shade-imposed reduction in Pfr levels induces increases in the abundance of PIF3, and mutant analysis indicates that PIF3 acts, in conjunction with PIF4 and PIF5, to promote the known shade-induced acceleration of hypocotyl elongation. Conversely

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

    NASA Astrophysics Data System (ADS)

    Shen, Bo-Wen

    2016-07-01

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

  14. Protective role of Commensals against Clostridium difficile Infection via an IL-1β-Mediated Positive Feedback Loop

    PubMed Central

    Hasegawa, Mizuho; Kamada, Nobuhiko; Jiao, Yizu; Liu, Meng Zhen; Núñez, Gabriel; Inohara, Naohiro

    2013-01-01

    Clostridium difficile (Cd) is a Gram-positive obligate anaerobic pathogen that causes pseudomembranous colitis in antibiotic-treated individuals. Commensal bacteria are known to have a significant role in the intestinal accumulation of Cd after antibiotic treatment, but little is known about how they affect host immunity during Cd infection. Here we report that Cd infection results in translocation of commensals across the intestinal epithelial barrier that is critical for neutrophil recruitment through the induction of an IL-1β-mediated positive feedback loop. Mice lacking ASC, an essential mediator of IL-1β and IL-18 processing and secretion, were highly susceptible to Cd infection. ASC−/− mice exhibited enhanced translocation of commensals to multiple organs after Cd infection. Notably, ASC−/− mice exhibited impaired CXCL1 production and neutrophil influx into intestinal tissues in response to Cd infection. The impairment in neutrophil recruitment resulted in reduced production of IL-1β and CXCL1, but not IL-18. Importantly, translocated commensals were required for ASC/Nlrp3-dependent IL-1β secretion by neutrophils. Mice lacking IL-1β were deficient in inducing CXCL1 secretion, suggesting that IL-1β is the dominant inducer of ASC-mediated CXCL1 production during Cd infection. These results indicate that translocated commensals play a crucial role in CXCL1-dependent recruitment of neutrophils to the intestine through an IL-1β/NLRP3/ASC-mediated positive feedback mechanism that is important for host survival and clearance of translocated commensals during Cd infection. PMID:22888139

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

    PubMed Central

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

    2016-01-01

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

  16. FGF signaling enhances a sonic hedgehog negative feedback loop at the initiation of spinal cord ventral patterning.

    PubMed

    Morales, Aixa V; Espeso-Gil, Sergio; Ocaña, Inmaculada; Nieto-Lopez, Francisco; Calleja, Elena; Bovolenta, Paola; Lewandoski, Mark; Diez Del Corral, Ruth

    2016-09-01

    A prevalent developmental mechanism for the assignment of cell identities is the production of spatiotemporal concentration gradients of extracellular signaling molecules that are interpreted by the responding cells. One of such signaling systems is the Shh gradient that controls neuronal subtype identity in the ventral spinal cord. Using loss and gain of function approaches in chick and mouse embryos, we show here that the fibroblast growth factor (FGF) signaling pathway is required to restrict the domains of ventral gene expression as neuroepithelial cells become exposed to Shh during caudal extension of the embryo. FGF signaling activates the expression of the Shh receptor and negative pathway regulator Patched 2 (Ptch2) and therefore can enhance a negative feedback loop that restrains the activity of the pathway. Thus, we identify one of the mechanisms by which FGF signaling acts as a modulator of the onset of Shh signaling activity in the context of coordination of ventral patterning and caudal axis extension. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 956-971, 2016. PMID:26600420

  17. RTVP-1 promotes mesenchymal transformation of glioma via a STAT-3/IL-6-dependent positive feedback loop

    PubMed Central

    Giladi, Nis David; Ziv-Av, Amotz; Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Ben-Asher, Hiba Waldman; deCarvalho, Ana; Mikkelsen, Tom; Poisson, Laila; Brodie, Chaya

    2015-01-01

    Glioblastomas (GBMs), the most aggressive primary brain tumors, exhibit increased invasiveness and resistance to anti-tumor treatments. We explored the role of RTVP-1, a glioma-associated protein that promotes glioma cell migration, in the mesenchymal transformation of GBM. Analysis of The Cancer Genome Atlas (TCGA) demonstrated that RTVP-1 expression was higher in mesenchymal GBM and predicted tumor recurrence and poor clinical outcome. ChiP analysis revealed that the RTVP-1 promoter binds STAT3 and C/EBPβ, two master transcription factors that regulate mesenchymal transformation of GBM. In addition, IL-6 induced RTVP-1 expression in a STAT3-dependent manner. RTVP-1 increased the migration and mesenchymal transformation of glioma cells. Similarly, overexpression of RTVP-1 in human neural stem cells induced mesenchymal differentiation, whereas silencing of RTVP-1 in glioma stem cells (GSCs) decreased the mesenchymal transformation and stemness of these cells. Silencing of RTVP-1 also increased the survival of mice bearing GSC-derived xenografts. Using gene array analysis of RTVP-1 silenced glioma cells we identified IL-6 as a mediator of RTVP-1 effects on the mesenchymal transformation and migration of GSCs, therefore acting in a positive feedback loop by upregulating RTVP-1 expression via the STAT3 pathway. Collectively, these results implicate RTVP-1 as a novel prognostic marker and therapeutic target in GBM. PMID:26267319

  18. Negative feedback loop between p66Shc and ZEB1 regulates fibrotic EMT response in lung cancer cells

    PubMed Central

    Li, X; Gao, D; Wang, H; Li, X; Yang, J; Yan, X; Liu, Z; Ma, Z

    2015-01-01

    The epithelial-to-mesenchymal transition (EMT) program is crucial for the epithelial cancer progression and fibrotic diseases. Our previous work has demonstrated that p66Shc, a focal adhesion-associated adaptor protein, is frequently downregulated in lung cancers and its depletion promotes metastasis behavior through anoikis resistance. However, mechanism underlying loss of p66Shc and EMT response is not fully understood. Here, we showed that p66Shc deficiency enhanced the expression of ZEB1, the known mesenchymal transcription factor and consequently increased Vimentin, and decreased epithelial markers of E-cadherin and β-catenin. p66Shc depletion also increased cell invasion and migration. In addition, ChIP and luciferase assays showed that these effects were directly mediated by ZEB1 repression of p66Shc promoter. Thus, our findings define a critical role of p66Shc in the suppression of fibrotic EMT response with a negative feedback loop between p66Shc and ZEB1 in lung epithelial cancer cells. PMID:25837484

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2013-04-23

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

  1. Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth.

    PubMed

    Ru, Peng; Hu, Peng; Geng, Feng; Mo, Xiaokui; Cheng, Chunming; Yoo, Ji Young; Cheng, Xiang; Wu, Xiaoning; Guo, Jeffrey Yunhua; Nakano, Ichiro; Lefai, Etienne; Kaur, Balveen; Chakravarti, Arnab; Guo, Deliang

    2016-08-01

    Dysregulated lipid metabolism is a characteristic of malignancies. Sterol regulatory element binding protein 1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is highly activated in malignancies. Here, we unraveled a link between miR-29 and the SCAP (SREBP cleavage-activating protein)/SREBP-1 pathway in glioblastoma (GBM) growth. Epidermal growth factor receptor (EGFR) signaling enhances miR-29 expression in GBM cells via upregulation of SCAP/SREBP-1, and SREBP-1 activates miR-29 expression via binding to specific sites in its promoter. In turn, miR-29 inhibits SCAP and SREBP-1 expression by interacting with their 3' UTRs. miR-29 transfection suppressed lipid synthesis and GBM cell growth, which were rescued by the addition of fatty acids or N-terminal SREBP-1 expression. Xenograft studies showed that miR-29 mimics significantly inhibit GBM growth and prolong the survival of GBM-bearing mice. Our study reveals a previously unrecognized negative feedback loop in SCAP/SREBP-1 signaling mediated by miR-29 and suggests that miR-29 treatment may represent an effective means to target GBM. PMID:27477273

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

    SciTech Connect

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

    2007-01-15

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-12-01

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

  5. Interactions between Shh, Sostdc1 and Wnt signaling and a new feedback loop for spatial patterning of the teeth.

    PubMed

    Cho, Sung-Won; Kwak, Sungwook; Woolley, Thomas E; Lee, Min-Jung; Kim, Eun-Jung; Baker, Ruth E; Kim, Hee-Jin; Shin, Jeon-Soo; Tickle, Cheryll; Maini, Philip K; Jung, Han-Sung

    2011-05-01

    Each vertebrate species displays specific tooth patterns in each quadrant of the jaw: the mouse has one incisor and three molars, which develop at precise locations and at different times. The reason why multiple teeth form in the jaw of vertebrates and the way in which they develop separately from each other have been extensively studied, but the genetic mechanism governing the spatial patterning of teeth still remains to be elucidated. Sonic hedgehog (Shh) is one of the key signaling molecules involved in the spatial patterning of teeth and other ectodermal organs such as hair, vibrissae and feathers. Sostdc1, a secreted inhibitor of the Wnt and Bmp pathways, also regulates the spatial patterning of teeth and hair. Here, by utilizing maternal transfer of 5E1 (an anti-Shh antibody) to mouse embryos through the placenta, we show that Sostdc1 is downstream of Shh signaling and suggest a Wnt-Shh-Sostdc1 negative feedback loop as a pivotal mechanism controlling the spatial patterning of teeth. Furthermore, we propose a new reaction-diffusion model in which Wnt, Shh and Sostdc1 act as the activator, mediator and inhibitor, respectively, and confirm that such interactions can generate the tooth pattern of a wild-type mouse and can explain the various tooth patterns produced experimentally. PMID:21447550

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  9. Impedance spectra of Fe-doped SrTiO3 thin films upon bias voltage: inductive loops as a trace of ion motion.

    PubMed

    Taibl, S; Fafilek, G; Fleig, J

    2016-08-01

    Mass and charge transport properties of slightly Fe-doped SrTiO3 (Fe:STO) thin films on a conducting substrate were investigated by means of impedance spectroscopy under different bias voltages and I-V measurements with varying scan rates. At measurement temperatures between 325 °C and 700 °C the applied bias voltage caused an unusual "inductive loop" in the low frequency range of impedance spectra. DC measurements showed that current-voltage curves strongly depend on the scan rate, indicating that different states of the sample became accessible to probe. Both findings can be understood in terms of bias induced ion motion, i.e. by stoichiometry polarization within the Fe:STO thin films upon voltage. Hence, the appearance of an "inductive loop" in the impedance spectra is considered a very general feature that might exist for many materials, particularly in oxide thin films. It may indicate ion motion and stoichiometry variations taking place in the corresponding frequency range. PMID:27088884

  10. Analysis of core circadian feedback loop in suprachiasmatic nucleus of mCry1-luc transgenic reporter mouse

    PubMed Central

    Maywood, Elizabeth S.; Drynan, Lesley; Chesham, Johanna E.; Edwards, Mathew D.; Dardente, Hugues; Fustin, Jean-Michel; Hazlerigg, David G.; O’Neill, John S.; Codner, Gemma F.; Smyllie, Nicola J.; Brancaccio, Marco; Hastings, Michael H.

    2013-01-01

    The suprachiasmatic nucleus (SCN) coordinates circadian rhythms that adapt the individual to solar time. SCN pacemaking revolves around feedback loops in which expression of Period (Per) and Cryptochrome (Cry) genes is periodically suppressed by their protein products. Specifically, PER/CRY complexes act at E-box sequences in Per and Cry to inhibit their transactivation by CLOCK/BMAL1 heterodimers. To function effectively, these closed intracellular loops need to be synchronized between SCN cells and to the light/dark cycle. For Per expression, this is mediated by neuropeptidergic and glutamatergic extracellular cues acting via cAMP/calcium-responsive elements (CREs) in Per genes. Cry genes, however, carry no CREs, and how CRY-dependent SCN pacemaking is synchronized remains unclear. Furthermore, whereas reporter lines are available to explore Per circadian expression in real time, no Cry equivalent exists. We therefore created a mouse, B6.Cg-Tg(Cry1-luc)01Ld, carrying a transgene (mCry1-luc) consisting of mCry1 elements containing an E-box and E′-box driving firefly luciferase. mCry1-luc organotypic SCN slices exhibited stable circadian bioluminescence rhythms with appropriate phase, period, profile, and spatial organization. In SCN lacking vasoactive intestinal peptide or its receptor, mCry1 expression was damped and desynchronized between cells. Despite the absence of CREs, mCry1-luc expression was nevertheless (indirectly) sensitive to manipulation of cAMP-dependent signaling. In mPer1/2-null SCN, mCry1-luc bioluminescence was arrhythmic and no longer suppressed by elevation of cAMP. Finally, an SCN graft procedure showed that PER-independent as well as PER-dependent mechanisms could sustain circadian expression of mCry1. The mCry1-luc mouse therefore reports circadian mCry1 expression and its interactions with vasoactive intestinal peptide, cAMP, and PER at the heart of the SCN pacemaker. PMID:23690615

  11. 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

  12. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-28

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

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

    PubMed Central

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

    2015-01-01

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

  16. 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

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

    SciTech Connect

    Garrison, Sean

    2009-05-21

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

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

    PubMed

    Hou, Yubin; Zhang, Qian; Wang, Pu

    2016-06-13

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

  19. 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

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

    PubMed

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

    2016-01-01

    Optogenetics provides a method of neuron stimulation that has high spatial, temporal, and cell-type specificity. Here we present a model of optogenetic feedback control that targets the inhibitory population, which expresses light-sensitive channelrhodopsin-2 channels, in a mean-field model of undifferentiated cortex that is driven to seizures. The inhibitory population is illuminated with an intensity that is a function of electrode measurements obtained via the cortical model. We test the efficacy of this control method on seizurelike activity observed in two parameter spaces of the cortical model that most closely correspond to seizures observed in patients. We also compare the effect of closed-loop and open-loop control on seizurelike activity using a less-complicated ordinary differential equation model of the undifferentiated cortex in parameter space. Seizurelike activity is successfully suppressed in both parameter planes using optimal illumination intensities less likely to have adverse effects on cortical tissue. PMID:26871110

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

    PubMed

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

    2014-12-01

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

  2. 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

  3. 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

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

    NASA Astrophysics Data System (ADS)

    Vachirasricirikul, Sitthidet; Ngamroo, Issarachai; Kaitwanidvilai, Somyot

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

  5. The insecticidal spider toxin SFI1 is a knottin peptide that blocks the pore of insect voltage-gated sodium channels via a large β-hairpin loop.

    PubMed

    Bende, Niraj S; Dziemborowicz, Sławomir; Herzig, Volker; Ramanujam, Venkatraman; Brown, Geoffrey W; Bosmans, Frank; Nicholson, Graham M; King, Glenn F; Mobli, Mehdi

    2015-03-01

    Spider venoms contain a plethora of insecticidal peptides that act on neuronal ion channels and receptors. Because of their high specificity, potency and stability, these peptides have attracted much attention as potential environmentally friendly insecticides. Although many insecticidal spider venom peptides have been isolated, the molecular target, mode of action and structure of only a small minority have been explored. Sf1a, a 46-residue peptide isolated from the venom of the tube-web spider Segesteria florentina, is insecticidal to a wide range of insects, but nontoxic to vertebrates. In order to investigate its structure and mode of action, we developed an efficient bacterial expression system for the production of Sf1a. We determined a high-resolution solution structure of Sf1a using multidimensional 3D/4D NMR spectroscopy. This revealed that Sf1a is a knottin peptide with an unusually large β-hairpin loop that accounts for a third of the peptide length. This loop is delimited by a fourth disulfide bond that is not commonly found in knottin peptides. We showed, through mutagenesis, that this large loop is functionally critical for insecticidal activity. Sf1a was further shown to be a selective inhibitor of insect voltage-gated sodium channels, consistent with its 'depressant' paralytic phenotype in insects. However, in contrast to the majority of spider-derived sodium channel toxins that function as gating modifiers via interaction with one or more of the voltage-sensor domains, Sf1a appears to act as a pore blocker. PMID:25559770

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

    PubMed

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

    2015-02-01

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

  7. Multiple feedback control apparatus for power conditioning equipment

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

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

  8. 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.

  9. 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.

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

    PubMed Central

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

    2015-01-01

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

  11. Regulatory effects of a Mnk2-eIF4E feedback loop during mTORC1 targeting of human medulloblastoma cells.

    PubMed

    Eckerdt, Frank; Beauchamp, Elspeth; Bell, Jonathan; Iqbal, Asneha; Su, Bing; Fukunaga, Rikiro; Lulla, Rishi R; Goldman, Stewart; Platanias, Leonidas C

    2014-09-30

    The mTOR pathway controls mRNA translation of mitogenic proteins and is a central regulator of metabolism in malignant cells. Development of malignant cell resistance is a limiting factor to the effects of mTOR inhibitors, but the mechanisms accounting for such resistance are not well understood. We provide evidence that mTORC1 inhibition by rapamycin results in engagement of a negative feedback regulatory loop in malignant medulloblastoma cells, involving phosphorylation of the eukaryotic translation-initiation factor eIF4E. This eIF4E phosphorylation is Mnk2- mediated, but Mnk1-independent, and acts as a survival mechanism for medulloblastoma cells. Pharmacological targeting of Mnk1/2 or siRNA-mediated knockdown of Mnk2 sensitizes medulloblastoma cells to mTOR inhibition and promotes suppression of malignant cell proliferation and anchorage-independent growth. Altogether, these findings provide evidence for the existence of a Mnk2-controlled feedback loop in medulloblastoma cells that accounts for resistance to mTOR inhibitors, and raise the potential for combination treatments of mTOR and Mnk inhibitors for the treatment of medulloblastoma. PMID:25193863

  12. 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.

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

    PubMed

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

    2016-03-01

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

  14. IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis

    PubMed Central

    Rokavec, Matjaz; Öner, Meryem Gülfem; Li, Huihui; Jackstadt, Rene; Jiang, Longchang; Lodygin, Dmitri; Kaller, Markus; Horst, David; Ziegler, Paul K.; Schwitalla, Sarah; Slotta-Huspenina, Julia; Bader, Franz G.; Greten, Florian R.; Hermeking, Heiko

    2014-01-01

    Members of the miR-34 family are induced by the tumor suppressor p53 and are known to inhibit epithelial-to-mesenchymal transition (EMT) and therefore presumably suppress the early phases of metastasis. Here, we determined that exposure of human colorectal cancer (CRC) cells to the cytokine IL-6 activates the oncogenic STAT3 transcription factor, which directly represses the MIR34A gene via a conserved STAT3-binding site in the first intron. Repression of MIR34A was required for IL-6–induced EMT and invasion. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6–dependent STAT3 activation, as a conserved, direct miR-34a target. The resulting IL-6R/STAT3/miR-34a feedback loop was present in primary colorectal tumors as well as CRC, breast, and prostate cancer cell lines and associated with a mesenchymal phenotype. An active IL-6R/STAT3/miR-34a loop was necessary for EMT, invasion, and metastasis of CRC cell lines and was associated with nodal and distant metastasis in CRC patient samples. p53 activation in CRC cells interfered with IL-6–induced invasion and migration via miR-34a–dependent downregulation of IL6R expression. In Mir34a-deficient mice, colitis-associated intestinal tumors displayed upregulation of p-STAT3, IL-6R, and SNAIL and progressed to invasive carcinomas, which was not observed in WT animals. Collectively, our data indicate that p53-dependent expression of miR-34a suppresses tumor progression by inhibiting a IL-6R/STAT3/miR-34a feedback loop. PMID:24642471

  15. 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.

  16. 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

  17. High voltage DC power supply

    DOEpatents

    Droege, T.F.

    1989-12-19

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

  18. High voltage DC power supply

    DOEpatents

    Droege, Thomas F.

    1989-01-01

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

  19. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

    Horan, D.

    1999-04-13

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

  2. 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.

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

    PubMed

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

    2014-07-01

    Tungstate, a compound with antidiabetic, antiobesity, and antihypertensive properties, activates the large-conductance voltage- and Ca(2+)-dependent K(+) (BK) channel containing either β1 or β4 subunits. The BK activation by tungstate is Mg(2+)-dependent and promotes arterial vasodilation, but only in precontracted mouse arteries expressing β1. In this study, we further explored how the β1 subunit participates in tungstate activation of BK channels. Activation of heterologously expressed human BKαβ1 channels in inside-out patches is fully dependent on the Mg(2+) sensitivity of the BK α channel subunit even at high (10 μM) cytosolic Ca(2+) concentration. Alanine mutagenesis of β1 extracellular residues Y74 or S104, which destabilize the active voltage sensor, greatly decreased the tungstate-induced left-shift of the BKαβ1 G-V curves in either the absence or presence of physiologically relevant cytosolic Ca(2+) levels (10 μM). The weakened tungstate activation of the BKαβ1Y74A and BKαβ1S104A mutant channels was not related to decreased Mg(2+) sensitivity. These results, together with previously published reports, support the idea that the putative binding site for tungstate-mediated BK channel activation is located in the pore-forming α channel subunit, around the Mg(2+) binding site. The role of β1 in tungstate-induced channel activation seems to rely on its interaction with the BK α subunit to modulate channel activity. Loop residues that are essential for the regulation of voltage sensor activation and gating of the BK channel are also relevant for BK activation by tungstate. PMID:24158430

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    PubMed

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

    2015-06-28

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

  6. Tongxinluo inhibits vascular inflammation and neointimal hyperplasia through blockade of the positive feedback loop between miR-155 and TNF-α.

    PubMed

    Zhang, Ruo-nan; Zheng, Bin; Li, Li-min; Zhang, Jing; Zhang, Xin-hua; Wen, Jin-kun

    2014-08-15

    Tongxinluo (TXL), a traditional Chinese medicine, has multiple vasoprotective effects, including anti-inflammation. MicroRNA-155 (miR-155) is involved in vascular inflammation and atherosclerosis. However, a direct relationship between TXL and miR-155 in the development of vascular inflammation and remodeling had not yet been shown. The objective of the present study was to investigate whether TXL exerts an inhibitory effect on the vascular inflammatory response and neointimal hyperplasia by regulating miR-155 expression. Using the carotid artery ligation model in mice, we have shown that TXL dose dependently inhibited neointimal formation and reduced the vascular inflammatory response by inhibiting inflammatory cytokine production and macrophage infiltration. miR-155 was induced by carotid artery ligation, and neointimal hyperplasia was strongly reduced in miR-155(−/−) mice. In contrast, miR-155 overexpression partly reversed the inhibitory effect of TXL on neointimal hyperplasia. In bone marrow-derived macrophages, miR-155 and TNF-α formed a positive feedback loop to promote the inflammatory response, which could be blocked by TXL. Furthermore, TXL increased Akt1 protein expression and phosphorylation in TNF-α-stimulated marrow-derived macrophages, and knockdown of Akt1 abrogated the TXL-induced suppression of miR-155. In conclusion, TXL inhibits the vascular inflammatory response and neointimal hyperplasia induced by carotid artery ligation in mice. Suppression of miR-155 expression mediated by Akt1 and blockade of the feedback loop between miR-155 and TNF-α are important pathways whereby TXL exerts its vasoprotective effects. PMID:24951754

  7. A Negative Feedback Loop Controlling bHLH Complexes Is Involved in Vascular Cell Division and Differentiation in the Root Apical Meristem.

    PubMed

    Katayama, Hirofumi; Iwamoto, Kuninori; Kariya, Yuka; Asakawa, Tomohiro; Kan, Toshiyuki; Fukuda, Hiroo; Ohashi-Ito, Kyoko

    2015-12-01

    Controlling cell division and differentiation in meristems is essential for proper plant growth. Two bHLH heterodimers consisting of LONESOME HIGHWAY (LHW) and TARGET OF MONOPTEROS 5 (TMO5)/TMO5-LIKE1 (T5L1) regulate periclinal cell division in vascular cells in the root apical meristem (RAM). In this study, we further investigated the functions of LHW-T5L1, finding that in addition to controlling cell division, this complex regulates xylem differentiation in the RAM via a novel negative regulatory system. LHW-T5L1 upregulated the thermospermine synthase gene ACAULIS5 (ACL5), as well as SUPPRESSOR OF ACAULIS5 LIKE3 (SACL3), which encodes a bHLH protein, in the RAM. The SACL3 promoter sequence contains a conserved upstream open reading frame (uORF), which blocked translation of the main SACL3 ORF in the absence of thermospermine. Thermospermine eliminated the negative effect of uORF and enhanced SACL3 production. Further genetic and molecular biological analyses indicated that ACL5 and SACL3 suppress the function of LHW-T5L1 through a protein-protein interaction between LHW and SACL3. Finally, we showed that a negative feedback loop consisting of LHW-T5L1, ACL5, SACL3, and LHW-SACL3 contributes to maintain RAM size and proper root growth. These findings suggest that a negative feedback loop regulates the LHW-T5L1 output level to coordinate cell division and differentiation in a cell-autonomous manner. PMID:26616019

  8. 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.

  9. 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.

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

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

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

  11. 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.

  12. 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.

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

    PubMed

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

    2015-05-10

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

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

    PubMed

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

    2016-02-10

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

  15. Rats' performance on variable-interval schedules with a linear feedback loop between response rate and reinforcement rate.

    PubMed Central

    Reed, Phil; Hildebrandt, Tom; DeJongh, Julie; Soh, Mariane

    2003-01-01

    Three experiments investigated whether rats are sensitive to the molar properties of a variable-interval (VI) schedule with a positive relation between response rate and reinforcement rate (i.e., a VI+ schedule). In Experiment 1, rats responded faster on a variable ratio (VR) schedule than on a VI+ schedule with an equivalent feedback function. Reinforced interresponse times (IRTs) were shorter on the VR as compared to the VI+ schedule. In Experiments 2 and 3, there was no systematic difference in response rates maintained by a VI+ schedule and a VI schedule yoked in terms of reinforcement rate. This was found both when the yoking procedure was between-subject (Experiment 2) and within-subject (Experiment 3). Mean reinforced IRTs were similar on both the VI+ and yoked VI schedules, but these values were more variable on the VI+ schedule. These results provided no evidence that rats are sensitive to the feedback function relating response rate to reinforcement rate on a VI+ schedule. PMID:12822684

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

    PubMed

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

    2015-09-18

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

  17. 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.

  18. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2014-01-01

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

  2. HGF/Met and FOXM1 Form a Positive Feedback Loop and Render Pancreatic Cancer Cells Resistance to Met Inhibition and Aggressive Phenotypes

    PubMed Central

    Cui, Jiujie; Xia, Tian; Xie, Dacheng; Gao, Yong; Jia, Zhiliang; Wei, Daoyan; Wang, Liang; Huang, Suyun; Quan, Ming; Xie, Keping

    2015-01-01

    Purpose Hepatocyte growth factor (HGF)/Met signaling plays 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. Experimental Design 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. Results 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 RAS/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. Conclusions 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. PMID:26876216

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

    PubMed Central

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

    2016-01-01

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

  4. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2012-07-01

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

  9. Fbw7 Repression by Hes5 Creates a Feedback Loop That Modulates Notch-Mediated Intestinal and Neural Stem Cell Fate Decisions

    PubMed Central

    Tendeng, Christian; Clurman, Bruce E.; Lewis, Julian; Behrens, Axel

    2013-01-01

    FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins. The Fbw7 locus comprises three different isoforms, each with its own promoter and each suspected to have a distinct set of substrates. Most FBW7 targets have important functions in developmental processes and oncogenesis, including Notch proteins, which are functionally important substrates of SCF(Fbw7). Notch signalling controls a plethora of cell differentiation decisions in a wide range of species. A prominent role of this signalling pathway is that of mediating lateral inhibition, a process where exchange of signals that repress Notch ligand production amplifies initial differences in Notch activation levels between neighbouring cells, resulting in unequal cell differentiation decisions. Here we show that the downstream Notch signalling effector HES5 directly represses transcription of the E3 ligase Fbw7β, thereby directly bearing on the process of lateral inhibition. Fbw7Δ/+ heterozygous mice showed haploinsufficiency for Notch degradation causing impaired intestinal progenitor cell and neural stem cell differentiation. Notably, concomitant inactivation of Hes5 rescued both phenotypes and restored normal stem cell differentiation potential. In silico modelling suggests that the NICD/HES5/FBW7β positive feedback loop underlies Fbw7 haploinsufficiency. Thus repression of Fbw7β transcription by Notch signalling is an essential mechanism that is coupled to and required for the correct specification of cell fates induced by lateral inhibition. PMID:23776410

  10. A systemic transcriptome analysis reveals the regulation of neural stem cell maintenance by an E2F1–miRNA feedback loop

    PubMed Central

    Palm, Thomas; Hemmer, Kathrin; Winter, Julia; Fricke, Inga B.; Tarbashevich, Katsiaryna; Sadeghi Shakib, Fereshteh; Rudolph, Ina-Maria; Hillje, Anna-Lena; De Luca, Paola; Bahnassawy, Lamia'a; Madel, Rabea; Viel, Thomas; De Siervi, Adriana; Jacobs, Andreas H.; Diederichs, Sven; Schwamborn, Jens C.

    2013-01-01

    Stem cell fate decisions are controlled by a molecular network in which transcription factors and miRNAs are of key importance. To systemically investigate their impact on neural stem cell (NSC) maintenance and neuronal commitment, we performed a high-throughput mRNA and miRNA profiling and isolated functional interaction networks of involved mechanisms. Thereby, we identified an E2F1–miRNA feedback loop as important regulator of NSC fate decisions. Although E2F1 supports NSC proliferation and represses transcription of miRNAs from the miR-17∼92 and miR-106a∼363 clusters, these miRNAs are transiently up-regulated at early stages of neuronal differentiation. In these early committed cells, increased miRNAs expression levels directly repress E2F1 mRNA levels and inhibit cellular proliferation. In mice, we demonstrated that these miRNAs are expressed in the neurogenic areas and that E2F1 inhibition represses NSC proliferation. The here presented data suggest a novel interaction mechanism between E2F1 and miR-17∼92 / miR-106a∼363 miRNAs in controlling NSC proliferation and neuronal differentiation. PMID:23396440

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

    PubMed Central

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

    2016-01-01

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

  12. Positive regulation of the Egr-1/osteopontin positive feedback loop in rat vascular smooth muscle cells by TGF-{beta}, ERK, JNK, and p38 MAPK signaling

    SciTech Connect

    Yu, Hong-Wei; Liu, Qi-Feng; Liu, Gui-Nan

    2010-05-28

    Previous studies identified a positive feedback loop in rat vascular smooth muscle cells (VSMCs) in which early growth response factor-1 (Egr-1) binds to the osteopontin (OPN) promoter and upregulates OPN expression, and OPN upregulates Egr-1 expression via the extracellular signal-regulated protein kinase (ERK) signaling pathway. The current study examined whether transforming growth factor-{beta} (TGF-{beta}) activity contributes to Egr-1 binding to the OPN promoter, and whether other signaling pathways act downstream of OPN to regulate Egr-1 expression. ChIP assays using an anti-Egr-1 antibody showed that amplification of the OPN promoter sequence decreased in TGF-{beta} DNA enzyme-transfected VSMCs relative to control VSMCs. Treatment of VSMCs with PD98059 (ERK inhibitor), SP600125 (JNK inhibitor), or SB203580 (p38 MAPK inhibitor) significantly inhibited OPN-induced Egr-1 expression, and PD98059 treatment was associated with the most significant decrease in Egr-1 expression. OPN-stimulated VSMC cell migration was inhibited by SP600125 or SB203580, but not by PD98059. Furthermore, MTT assays showed that OPN-mediated cell proliferation was inhibited by PD98059, but not by SP600125 or SB203580. Taken together, the results of the current study show that Egr-1 binding to the OPN promoter is positively regulated by TGF-{beta}, and that the p38 MAPK, JNK, and ERK pathways are involved in OPN-mediated Egr-1 upregulation.

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

    PubMed Central

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

    2015-01-01

    Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. MiR-190a belongs to the small noncoding RNA family and has an important role in breast cancer metastasis. However, it is still unknown whether miR-190a plays a role in prostate cancer development. Herein, we first observed AR/miR-190a/YB-1 forms an auto-regulatory negative feedback loop in prostate cancer: miR-190a expression was down-regulated by AR activation; YB-1 functions are as an AR activator; miR-190a inhibited AR expression and transactivation through direct binding to 3′UTR of YB-1 gene. MiR-190a contributes the human prostate cancer cell growth through AR-dependent signaling. Moreover, we examined the expression of miR-190a and observed a significant decrease in human prostate cancers. Reduced expression of miR-190a was inversely correlated to AR levels of prostate cancer patients, and patients with higher miR-190a expression in their tumor have improved tumor-free survival. Taken together, our findings identified a biochemical and functional link between miR-190a with reduced expression in advanced prostate cancer, YB-1 and AR signaling in prostate cancer. PMID:26314494

  14. 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

  15. HD-Zip Proteins GL2 and HDG11 Have Redundant Functions in Arabidopsis Trichomes, and GL2 Activates a Positive Feedback Loop via MYB23[W

    PubMed Central

    Khosla, Aashima; Paper, Janet M.; Boehler, Allison P.; Bradley, Amanda M.; Neumann, Titus R.; Schrick, Kathrin

    2014-01-01

    The class IV homeodomain leucine zipper transcription factor GLABRA2 (GL2) acts in a complex regulatory circuit that regulates the differentiation of trichomes in Arabidopsis thaliana. We describe a genetic interaction with HOMEODOMAIN GLABROUS11 (HDG11), previously identified as a negative regulator of trichome branching. gl2 hdg11 double mutants display enhanced trichome cell-type differentiation defects. Transgenic expression of HDG11 using the GL2 promoter partially suppresses gl2 trichome phenotypes. Vice versa, expression of GL2 under the control of its native promoter partially complements hdg11 ectopic branching. Since gl2 hdg11 and gl2 myb23 double mutants and the triple mutant display similar trichome differentiation defects, we investigated a connection to the R2R3-MYB transcription factor MYB23. We show that MYB23 transcript levels are significantly reduced in shoots from gl2 mutants and that GL2 can drive the expression of a MYB23-promoter fusion to green fluorescent protein. Yeast one-hybrid, chromatin immunoprecipitation, and in planta reporter gene experiments indicate that an L1-box in the MYB23 promoter acts as a GL2 binding site. Taken together, our findings reveal a functional redundancy between GL2 and HDG11, two homeodomain leucine zipper transcription factors previously thought to mediate opposing functions in trichome morphogenesis. A model is proposed in which GL2 transcript levels are maintained through a positive feedback loop involving GL2 activation of MYB23. PMID:24824485

  16. miR-200c-SUMOylated KLF4 feedback loop acts as a switch in transcriptional programs that control VSMC proliferation.

    PubMed

    Zheng, Bin; Bernier, Michel; Zhang, Xin-hua; Suzuki, Toru; Nie, Chan-quan; Li, Yong Hui; Zhang, Yong; Song, Li-Li; Shi, Hui-jing; Liu, Yan; Zheng, Cui-ying; Wen, Jin-kun

    2015-05-01

    The regulation of vascular smooth muscle cell (VSMC) proliferation is an important issue because it has major implications for the prevention of pathological vascular conditions. Using microRNA array screen, we found the expression levels of 200 unique miRNAs in hyperplasic tissues. Among them, miR-200c expression substantially was down-regulated. The objective of this work was to assess the function of miR-200c and SUMOylated Krϋppel-like transcription factor 4 (KLF4) in the regulation of VSMC proliferation in both cultured cells and animal models of balloon injury. Under basal conditions, we found that miR-200c inhibited the expression of KLF4 and the SUMO-conjugating enzyme Ubc9. Upon PDGF-BB treatment, Ubc9 interacted with and promoted the SUMOylation of KLF4, which allowed the recruitment of transcriptional corepressors (e.g., nuclear receptor corepressor (NCoR) and HDAC2) to the miR-200c promoter. The reduction in miR-200c levels led to increased target gene expression (e.g., Ubc9 and KLF4), which further repressed miR-200c levels and accelerated VSMC proliferation. These results demonstrate that induction of a miR-200c-SUMOylated KLF4 feedback loop is a significant aspect of the PDGF-BB proliferative response in VSMCs and that targeting Ubc9 represents a novel approach for the prevention of restenosis. PMID:25791170

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-11-30

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

  1. Frequency chirp and mode partition induced mutual constraint on the side-band phase noise of a mode-locking WRC-FPLD fiber ring self-started with a lengthened feedback loop

    NASA Astrophysics Data System (ADS)

    Lin, Chun-Ju; Lin, Gong-Ru

    2013-04-01

    The specific mutual constraint effect of frequency chirp and mode partition on the side-band phase noise and timing jitter is theoretically and experimentally analyzed in a harmonically mode-locked weak-resonant-cavity Fabry-Perot laser diode (WRC-FPLD) fiber ring self-started by fiber-coupled optoelectronic feedback at 10 GHz with a lengthened loop. By inserting a 100 m long single-mode fiber into the feedback loop to self-start the mode-locking, minimal single-side-band phase noise of -70 dBc Hz-1 and -125 dBc Hz-1 are obtained at 100 Hz and 1 MHz offset, respectively. The optimized pulse-train exhibits a timing jitter of 0.67 ps and a pulsewidth of 18.5 ps. A significant degradation is observed for feedback loop lengths longer than 200 m due to the enhanced mode-partition noise contributed by the fiber-ring cavity incorporated in the WRC-FPLD. The theoretical model shows that the mutually coupled fiber-ring cavity and the optoelectronic feedback loop could provide a mode-locking pulse with a minimum phase noise of -135 dBc Hz-1 under the compromise of phase noise responses between the fiber-ring cavity and the feedback loop. These two factors hinder the improvement expected from the longer feedback loop and higher Q-value because the mode-partition noise is greatly enlarged when the multi-mode pulse experiences serious dispersion during distant transmission in the fiber. Under such a mutual constraint, the optimized return-to-zero (RZ) pulsed carrier is on-off keying (OOK) non-RZ data by 10 Gbit s-1, showing a high signal to noise ratio of 11 dB to achieve a receiving sensitivity of -19.2 dBm at a bit error rate (BER) of 10-9. When using the RZ pulsed carrier for data transmission at 10 Gbit s-1 in a passive optical network with a dense wavelength division multiplexing channelization of 200 GHz, the RZ-OOK data-stream still exhibits an error-free performance at a receiving power sensitivity as low as -17 dBm, even though a power penalty of 2.5 dB is added into

  2. Regulation loops for the ring magnet power supplies in the SSC accelerator complex

    SciTech Connect

    Tacconi, E.; Christiansen, C.

    1993-05-01

    The SSC complex consists of five cascaded accelerators: The linear accelerator (linac) and four synchrotrons: The low energy booster (LEB), the medium energy booster (MEB), the high energy booster (HEB), and the collider. Twelve- or 24-pulse phase-controlled SCR power supplies are used to energize the ring magnets. Each power supply has a voltage loop designed to regulate the voltage applied to the magnets. The voltage regulation loops for these synchrotrons and the current regulation for the LEB are analyzed in this work. The digital voltage regulator is fiber-optic isolated from the power converter. It has a closed-loop bandwidth of 150 Hz with band rejections for 60-Hz and 120-Hz perturbations. The LEB has a very precise current regulation system composed of a feedforward compensator, a fast feedback regulator, and a slow synchronous regulator. The current regulation design is corroborated by computer simulations.

  3. A theoretical model of slow wave regulation using voltage-dependent synthesis of inositol 1,4,5-trisphosphate.

    PubMed Central

    Imtiaz, Mohammad S; Smith, David W; van Helden, Dirk F

    2002-01-01

    A qualitative mathematical model is presented that examines membrane potential feedback on synthesis of inositol 1,4,5-trisphosphate (IP(3)), and its role in generation and modulation of slow waves. Previous experimental studies indicate that slow waves show voltage dependence, and this is likely to result through membrane potential modulation of IP(3). It is proposed that the observed response of the tissue to current pulse, pulse train, and maintained current injection can be explained by changes in IP(3), modulated through a voltage-IP(3) feedback loop. Differences underlying the tissue responses to current injections of opposite polarities are shown to be due to the sequence of events following such currents. Results from this model are consistent with experimental findings and provide further understanding of these experimental observations. Specifically, we find that membrane potential can induce, abolish, and modulate slow wave frequency by altering the excitability of the tissue through the voltage-IP(3) feedback loop. PMID:12324409

  4. CaCDPK15 positively regulates pepper responses to Ralstonia solanacearum inoculation and forms a positive-feedback loop with CaWRKY40 to amplify defense signaling.

    PubMed

    Shen, Lei; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Cheng, Wei; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Mou, Shaoliang; Liu, Zhiqin; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-01-01

    CaWRKY40 is a positive regulator of pepper (Capsicum annum) response to Ralstonia solanacearum inoculation (RSI), but the underlying mechanism remains largely unknown. Here, we functionally characterize CaCDPK15 in the defense signaling mediated by CaWRKY40. Pathogen-responsive TGA, W, and ERE boxes were identified in the CaCDPK15 promoter (pCaCDPK15), and pCaCDPK15-driven GUS expression was significantly enhanced in response to RSI and exogenously applied salicylic acid, methyl jasmonate, abscisic acid, and ethephon. Virus-induced gene silencing (VIGS) of CaCDPK15 significantly increased the susceptibility of pepper to RSI and downregulated the immunity-associated markers CaNPR1, CaPR1, and CaDEF1. By contrast, transient CaCDPK15 overexpression significantly activated hypersensitive response associated cell death, upregulated the immunity-associated marker genes, upregulated CaWRKY40 expression, and enriched CaWRKY40 at the promoters of its targets genes. Although CaCDPK15 failed to interact with CaWRKY40, the direct binding of CaWRKY40 to pCaCDPK15 was detected by chromatin immunoprecipitation, which was significantly potentiated by RSI in pepper plants. These combined results suggest that RSI in pepper induces CaCDPK15 and indirectly activates downstream CaWRKY40, which in turn potentiates CaCDPK15 expression. This positive-feedback loop would amplify defense signaling against RSI and efficiently activate strong plant immunity. PMID:26928570

  5. 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

  6. 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

  7. A detection of Milankovitch frequencies in tephra records of arc volcanism: Shedding light on a feedback loop between climate and volcanism. (Invited)

    NASA Astrophysics Data System (ADS)

    Kutterolf, S.; Jegen, M.; Schindlbeck, J. C.; Mitrovica, J. X.; Kwasnitschka, T.; Freundt, A.; Huybers, P. J.

    2013-12-01

    Although it is well understood that volcanism can impact global climate or tectonics can influence volcanism, it is less well appreciated that climate can influence volcanism. In this regard, both regional and global studies have provided compelling evidence that ice age loading processes modulate the frequency of volcanic eruption. However, a rigorous detection of Milankovitch periodicities in global volcanic output across the Pleistocene-Holocene ice age, which would firmly establish a connection between ice age climate and eruption frequency, has remained elusive. To this end, we report on a spectral analysis of a large number of well-preserved ash plume deposits recorded in marine sediments along the Pacific Ring of Fire, which accounts for about half of the global length of 44,000 km of active subduction. Eruptions at arc volcanoes tend to be highly explosive. We analyze the Pleistocene-to-Recent marine records of widespread tephras of sub-Plinian to Plinian, and occasionally co-ignimbrite, origin since they provide a well-preserved record of how eruption frequencies varied with depth (and, hence time). Our analysis yields a statistically significant detection of spectral peaks at the obliquity period. We propose that the variability in volcanic activity results from crustal stress changes associated with ice age mass redistribution. In particular, increased volcanism lags behind the highest rate of increasing eustatic sea level (decreasing global ice volume) by 4.0 × 3.6 kyr and correlates well with numerical predictions of stress changes at volcanically active sites. Our results strongly support the presence of a coupling between ice age climate, volcanism and the continental stress field. In future work we will incorporate longer tephra time series and more accurate age controls in order to improve - and widen - our detection of Milankovitch periodicities thus further elucidating the feedback loop between climate and volcanism as well as tectonics.

  8. The cotton MYB108 forms a positive feedback regulation loop with CML11 and participates in the defense response against Verticillium dahliae infection.

    PubMed

    Cheng, Huan-Qing; Han, Li-Bo; Yang, Chun-Lin; Wu, Xiao-Min; Zhong, Nai-Qin; Wu, Jia-He; Wang, Fu-Xin; Wang, Hai-Yun; Xia, Gui-Xian

    2016-04-01

    Accumulating evidence indicates that plant MYB transcription factors participate in defense against pathogen attack, but their regulatory targets and related signaling processes remain largely unknown. Here, we identified a defense-related MYB gene (GhMYB108) from upland cotton (Gossypium hirsutum) and characterized its functional mechanism. Expression of GhMYB108 in cotton plants was induced by Verticillium dahliae infection and responded to the application of defense signaling molecules, including salicylic acid, jasmonic acid, and ethylene. Knockdown of GhMYB108 expression led to increased susceptibility of cotton plants to V. dahliae, while ecotopic overexpression of GhMYB108 in Arabidopsis thaliana conferred enhanced tolerance to the pathogen. Further analysis demonstrated that GhMYB108 interacted with the calmodulin-like protein GhCML11, and the two proteins form a positive feedback loop to enhance the transcription of GhCML11 in a calcium-dependent manner. Verticillium dahliae infection stimulated Ca(2+) influx into the cytosol in cotton root cells, but this response was disrupted in both GhCML11-silenced plants and GhMYB108-silenced plants in which expression of several calcium signaling-related genes was down-regulated. Taken together, these results indicate that GhMYB108 acts as a positive regulator in defense against V. dahliae infection by interacting with GhCML11. Furthermore, the data also revealed the important roles and synergetic regulation of MYB transcription factor, Ca(2+), and calmodulin in plant immune responses. PMID:26873979

  9. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26503785

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

    PubMed

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

    2016-01-01

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

  12. Deregulation of NF-кB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy.

    PubMed

    Yousefzadeh, Nasibeh; Alipour, Mohammad Reza; Soufi, Farhad Ghadiri

    2015-03-01

    The current study was designed to explore whether microRNA-146a and its adapter proteins (tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1)) are involved in the pathogenesis of diabetes neuropathy. Twelve male Sprague Dawley rats were randomized into control and diabetic groups (n = 6). Diabetes was induced by a single-dose injection of nicotinamide (110 mg/kg; i.p.), 15 min before injection of streptozotocin (50 mg/kg; i.p.) in 12-h-fasted rats. Diabetic neuropathy was evaluated by hot plate and tail emersion tests, 2 months after the injection of streptozotocin. The gene expression level of microRNA-146a (miR-146a), IRAK1, TRAF6, and nuclear factor kappa B (NF-κB) was measured in the sciatic nerve of rats using the real time-PCR method. Moreover, the activity of NF-κB and the concentration of pro-inflammatory cytokines were determined by the ELISA method. In comparison with the control group, a threefold increase in the expression of miR-146a and NF-κB, and a twofold decrease in the expression of TRAF6 were observed in the sciatic nerve of diabetic rats. Furthermore, the NF-κB activity and the concentration of TNF-α, interleukin 6 (IL-6), and interleukin 1β (IL-1β) in the sciatic nerve of diabetic rats were higher than in those of control counterparts. These results suggest that a defect in the NF-кB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy. PMID:25567745

  13. A Regulatory Feedback Loop Between Ca2+/Calmodulin-dependent Protein Kinase Kinase 2 (CaMKK2) and the Androgen Receptor in Prostate Cancer Progression*

    PubMed Central

    Karacosta, Loukia G.; Foster, Barbara A.; Azabdaftari, Gissou; Feliciano, David M.; Edelman, Arthur M.

    2012-01-01

    The androgen receptor (AR) plays a critical role in prostate cancer (PCa) progression, however, the molecular mechanisms by which the AR regulates cell proliferation in androgen-dependent and castration-resistant PCa are incompletely understood. We report that Ca2+/calmodulin-dependent kinase kinase 2 (CaMKK2) expression increases and becomes nuclear or perinuclear in advanced PCa. In the TRAMP (transgenic adenocarcinoma of mouse prostate) model of PCa, CaMKK2 expression increases with PCa progression with many cells exhibiting nuclear staining. CaMKK2 expression is higher in human castration-resistant tumor xenografts compared with androgen-responsive xenografts and is markedly higher in the AR-expressing, tumorigenic cell line LNCaP compared with cell lines that are AR-nonexpressing and/or nontumorigenic. In LNCaP cells, dihydrotestosterone induced CaMKK2 mRNA and protein expression and translocation of CaMKK2 to the nucleus. Conversely, androgen withdrawal suppressed CaMKK2 expression. Knockdown of CaMKK2 expression by RNAi reduced LNCaP cell proliferation and increased percentages of cells in G1 phase, whereas correspondingly reducing percentages in S phase, of the cell cycle. CaMKK2 knockdown reduced expression of the AR target gene prostate-specific antigen at both mRNA and protein levels, AR transcriptional activity driven by androgen responsive elements from the prostate-specific probasin gene promoter and levels of the AR-regulated cell cycle proteins, cyclin D1 and hyperphosphorylated Rb. Our results suggest that in PCa progression, CaMKK2 and the AR are in a feedback loop in which CaMKK2 is induced by the AR to maintain AR activity, AR-dependent cell cycle control, and continued cell proliferation. PMID:22654108

  14. A regulatory feedback loop between Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and the androgen receptor in prostate cancer progression.

    PubMed

    Karacosta, Loukia G; Foster, Barbara A; Azabdaftari, Gissou; Feliciano, David M; Edelman, Arthur M

    2012-07-13

    The androgen receptor (AR) plays a critical role in prostate cancer (PCa) progression, however, the molecular mechanisms by which the AR regulates cell proliferation in androgen-dependent and castration-resistant PCa are incompletely understood. We report that Ca(2+)/calmodulin-dependent kinase kinase 2 (CaMKK2) expression increases and becomes nuclear or perinuclear in advanced PCa. In the TRAMP (transgenic adenocarcinoma of mouse prostate) model of PCa, CaMKK2 expression increases with PCa progression with many cells exhibiting nuclear staining. CaMKK2 expression is higher in human castration-resistant tumor xenografts compared with androgen-responsive xenografts and is markedly higher in the AR-expressing, tumorigenic cell line LNCaP compared with cell lines that are AR-nonexpressing and/or nontumorigenic. In LNCaP cells, dihydrotestosterone induced CaMKK2 mRNA and protein expression and translocation of CaMKK2 to the nucleus. Conversely, androgen withdrawal suppressed CaMKK2 expression. Knockdown of CaMKK2 expression by RNAi reduced LNCaP cell proliferation and increased percentages of cells in G(1) phase, whereas correspondingly reducing percentages in S phase, of the cell cycle. CaMKK2 knockdown reduced expression of the AR target gene prostate-specific antigen at both mRNA and protein levels, AR transcriptional activity driven by androgen responsive elements from the prostate-specific probasin gene promoter and levels of the AR-regulated cell cycle proteins, cyclin D1 and hyperphosphorylated Rb. Our results suggest that in PCa progression, CaMKK2 and the AR are in a feedback loop in which CaMKK2 is induced by the AR to maintain AR activity, AR-dependent cell cycle control, and continued cell proliferation. PMID:22654108

  15. 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

  16. The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis

    PubMed Central

    Nishimura, Tomoyasu; Zhao, Xiaomin; Gan, Huixian; Koyasu, Shigeo; Remold, Heinz G.

    2013-01-01

    Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Previously, we reported that in macrophages (Mφs), infection with avirulent Mtb H37Ra resulted in inhibition of necrosis by an inhibitory effect on mitochondrial permeability transition via the PGE2 receptor EP2. However, human Mφs also express EP4, a PGE2 receptor functionally closely related to EP2 that also couples to stimulatory guanine nucleotide binding protein, but the functional differences between EP2 and EP4 in Mtb-infected Mφs have been unclear. EP4 antagonist addition to H37Ra-infected Mφs inhibited the expression of cyclooxygenase 2 (COX2) and microsomal prostaglandin E synthase-1 (mPGES-1), which are involved in PGE2 production. Moreover, H37Ra infection induced PGE2 production through the Toll-like receptor (TLR) 2/p38 mitogen-activated protein kinase (MAPK) signaling pathway. Induction of COX2 and mPGES-1 expression by TLR2 stimulation or Mtb infection was increased after additional stimulation with EP4 agonist. Hence, in Mtb-infected Mφs, PGE2 production induced by pathogen recognition receptors/p38 MAPK signaling is up-regulated by EP4-triggered signaling to maintain an effective PGE2 concentration.—Nishimura, T., Zhao, X., Gan, H., Koyasu, S., and Remold, H. G. The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis. PMID:23759445

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

    PubMed Central

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

    2016-01-01

    Sustained activation of nuclear factor-κB (NF-κB) in cancer cells has been shown to promote inflammation, expansion of cancer stem cell (CSC) population, and tumor development. In contrast, recent studies reveal that CSCs exhibit increased inflammation due to constitutive NF-κB activation; however, the underlying molecular mechanism remains unclear. In the present study, the analysis of microarray data revealed upregulation of NF-κB-regulated pro-inflammatory genes and downregulation of copper metabolism MURR1 domain-containing 1 (COMMD1) during the enrichment for stemness in SAS head and neck squamous-cell carcinoma (HNSCC) cells. The 3′-UTR of COMMD1 mRNA contains microRNA (miR)-205 target site. Parallel studies with HNSCC and NSCLC cells indicated that miR-205 is upregulated upon NF-κB activation and suppresses COMMD1 expression in stemness-enriched cancer cells. COMMD1 negatively regulates the inflammatory responses induced by TLR agonists, IL-1β, and TNF-α by targeting RelA for degradation. The shRNA-mediated downregulation of COMMD1 in cancer cells enhanced inflammatory response, generating favorable conditions for macrophage recruitment. In addition, genes associated with stemness were also upregulated in these cells, which exhibited increased potential for anchorage-independent growth. Furthermore, COMMD1 downregulation promoted in vivo tumorigenesis and tumor growth, and tumors derived from COMMD1-knockdown cells displayed elevated level of NF-κB activation, increased expression of inflammatory- and stemness-associated genes, and contain expanded population of tumor-associated leukocytes and stemness-enriched cancer cells. These results suggest that COMMD1 downregulation by miR-205 promotes tumor development by modulating a positive feedback loop that amplifies inflammatory- and stemness-associated properties of cancer cells. PMID:26586569

  18. CaCDPK15 positively regulates pepper responses to Ralstonia solanacearum inoculation and forms a positive-feedback loop with CaWRKY40 to amplify defense signaling

    PubMed Central

    Shen, Lei; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Cheng, Wei; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Mou, Shaoliang; Liu, Zhiqin; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-01-01

    CaWRKY40 is a positive regulator of pepper (Capsicum annum) response to Ralstonia solanacearum inoculation (RSI), but the underlying mechanism remains largely unknown. Here, we functionally characterize CaCDPK15 in the defense signaling mediated by CaWRKY40. Pathogen-responsive TGA, W, and ERE boxes were identified in the CaCDPK15 promoter (pCaCDPK15), and pCaCDPK15-driven GUS expression was significantly enhanced in response to RSI and exogenously applied salicylic acid, methyl jasmonate, abscisic acid, and ethephon. Virus-induced gene silencing (VIGS) of CaCDPK15 significantly increased the susceptibility of pepper to RSI and downregulated the immunity-associated markers CaNPR1, CaPR1, and CaDEF1. By contrast, transient CaCDPK15 overexpression significantly activated hypersensitive response associated cell death, upregulated the immunity-associated marker genes, upregulated CaWRKY40 expression, and enriched CaWRKY40 at the promoters of its targets genes. Although CaCDPK15 failed to interact with CaWRKY40, the direct binding of CaWRKY40 to pCaCDPK15 was detected by chromatin immunoprecipitation, which was significantly potentiated by RSI in pepper plants. These combined results suggest that RSI in pepper induces CaCDPK15 and indirectly activates downstream CaWRKY40, which in turn potentiates CaCDPK15 expression. This positive-feedback loop would amplify defense signaling against RSI and efficiently activate strong plant immunity. PMID:26928570

  19. 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

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

    PubMed

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

    2016-05-01

    Sustained activation of nuclear factor-κB (NF-κB) in cancer cells has been shown to promote inflammation, expansion of cancer stem cell (CSC) population, and tumor development. In contrast, recent studies reveal that CSCs exhibit increased inflammation due to constitutive NF-κB activation; however, the underlying molecular mechanism remains unclear. In the present study, the analysis of microarray data revealed upregulation of NF-κB-regulated pro-inflammatory genes and downregulation of copper metabolism MURR1 domain-containing 1 (COMMD1) during the enrichment for stemness in SAS head and neck squamous-cell carcinoma (HNSCC) cells. The 3'-UTR of COMMD1 mRNA contains microRNA (miR)-205 target site. Parallel studies with HNSCC and NSCLC cells indicated that miR-205 is upregulated upon NF-κB activation and suppresses COMMD1 expression in stemness-enriched cancer cells. COMMD1 negatively regulates the inflammatory responses induced by TLR agonists, IL-1β, and TNF-α by targeting RelA for degradation. The shRNA-mediated downregulation of COMMD1 in cancer cells enhanced inflammatory response, generating favorable conditions for macrophage recruitment. In addition, genes associated with stemness were also upregulated in these cells, which exhibited increased potential for anchorage-independent growth. Furthermore, COMMD1 downregulation promoted in vivo tumorigenesis and tumor growth, and tumors derived from COMMD1-knockdown cells displayed elevated level of NF-κB activation, increased expression of inflammatory- and stemness-associated genes, and contain expanded population of tumor-associated leukocytes and stemness-enriched cancer cells. These results suggest that COMMD1 downregulation by miR-205 promotes tumor development by modulating a positive feedback loop that amplifies inflammatory- and stemness-associated properties of cancer cells. PMID:26586569

  1. EGR1, EGR2, and EGR3 activate the expression of their coregulator NAB2 establishing a negative feedback loop in cells of neuroectodermal and epithelial origin

    PubMed Central

    Kumbrink, Joerg; Kirsch, Kathrin H.; Johnson, Judith P.

    2010-01-01

    The inducible zinc finger transcription factors EGR1, EGR2, and EGR3 regulate the expression of numerous genes involved in differentiation, growth, and response to extracellular signals. Their activity is modulated in part through NAB2 which is induced by the same stimuli. In melanoma and carcinoma cells EGR1 activates NAB2 expression. In T lymphocytes EGR2 and EGR3 have been shown to inhibit NAB2 expression. Therefore, we investigated the influence of EGR2 and EGR3 on NAB2 expression in melanoma and carcinoma cells. Here we show that like EGR1, EGR2 and EGR3 induce NAB2 expression in these cells. EGR1 and EGR3 act in concert on the NAB2 promoter and are more potent activators of NAB2 transcription than EGR2. EGR1-, EGR2-, and EGR3-induced NAB2 promoter activity is mediated through similar cis-regulatory elements and the activation by each EGR is repressed by NAB2. Kinetic studies suggest that induction of EGR1 leads to low NAB2 expression while EGR2 and EGR3 are necessary for maximal and sustained expression. As aleady shown for EGR1, reduction of EGR2 or EGR3 expression by siRNAs reduced endogenous NAB2 levels. Depletion of EGR3 also resulted in a reduction of EGR2 levels confirming EGR2 as a target gene of EGR3. Our results suggest that in many cells of neuroectodermal and epithelial origin EGR1, EGR2, and EGR3 activate NAB2 transcription which is in turn is repressed by NAB2, thus establishing a negative feedback loop. This points to a complex relationship between the EGR factors and NAB2 expression likely depending on the cellular context. PMID:20506119

  2. Static inverter with synchronous output waveform synthesized by time-optimal-response feedback

    NASA Technical Reports Server (NTRS)

    Kernick, A.; Stechschulte, D. L.; Shireman, D. W.

    1976-01-01

    Time-optimal-response 'bang-bang' or 'bang-hang' technique, using four feedback control loops, synthesizes static-inverter sinusoidal output waveform by self-oscillatory but yet synchronous pulse-frequency-modulation (SPFM). A single modular power stage per phase of ac output entails the minimum of circuit complexity while providing by feedback synthesis individual phase voltage regulation, phase position control and inherent compensation simultaneously for line and load disturbances. Clipped sinewave performance is described under off-limit load or input voltage conditions. Also, approaches to high power levels, 3-phase arraying and parallel modular connection are given.

  3. 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.

  4. EB-virus latent membrane protein 1 potentiates the stemness of nasopharyngeal carcinoma via preferential activation of PI3K/AKT pathway by a positive feedback loop.

    PubMed

    Yang, C-F; Yang, G-D; Huang, T-J; Li, R; Chu, Q-Q; Xu, L; Wang, M-S; Cai, M-D; Zhong, L; Wei, H-J; Huang, H-B; Huang, J-L; Qian, C-N; Huang, B-J

    2016-06-30

    Our previous study reported that Epstein-Barr virus(EBV)-encoded latent membrane protein 1 (LMP1) could induce development of CD44(+/High) stem-like cells in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms that underlie modulation of cancer stem cells (CSCs) in NPC remain unclear. Here, we show that LMP1 induced CSC-like properties through promotion of the expression of epithelial-mesenchymal transition-like cellular markers and through alterations in differentiation markers. Furthermore, LMP1 activated and triggered phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, which subsequently stimulated expression of CSC markers, development of side population and tumor sphere formation. This suggests that PI3K/AKT pathway has an important role in the induction and maintenance of CSC properties in NPC. Similarly, PI3K/AKT pathway was also activated by phosphorylase in LMP1-induced CD44(+/High) cells. In addition, LMP1 greatly increased expression of miR-21 and downregulated expression of the miR-21 target, PTEN. Overexpression of miR-21 by transfection of miR-21 mimics into LMP1-transformed cells led to phosphorylase-mediated activation of the PI3K/AKT pathway and induction of CSCs. On the contrary, phosphorylation of the PI3K/AKT pathway and the expression of CSC were reversed by an miR-21 inhibitor. The specific inhibitor (Ly294002) of PI3K/AKT pathway significantly decreased expression of miR-21 and CSC markers and upregulated the expression of PTEN, which indicates that miR-21 and PTEN are the downstream effectors of PI3K/AKT and that expression of these two effectors are related to the development of NPC CSCs. Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and have a key role in LMP1-induced CSCs in NPC. PMID:26568302

  5. FOXP3 controls an miR-146/NFκB negative feedback loop that inhibits apoptosis in breast cancer cells

    PubMed Central

    Liu, Runhua; Liu, Cong; Chen, Dongquan; Yang, Wei-Hsiung; Liu, Xiuping; Liu, Chang-Gong; Dugas, Courtney M.; Tang, Fei; Zheng, Pan; Liu, Yang; Wang, Lizhong

    2015-01-01

    FOXP3 functions not only as the master regulator in regulatory T cells but also as an X-linked tumor suppressor. The tumor suppressive activity of FOXP3 has been observed in tumor initiation, but its role during tumor progression remains controversial. Moreover, the mechanism of FOXP3-mediated tumor suppressive activity remains largely unknown. Using chromatin immunoprecipitation sequencing, we identified a series of potential FOXP3-targeted microRNAs (miRs) in MCF7 cells. Notably, FOXP3 significantly induced the expression of miR-146a/b. In vitro, FOXP3-induced miR-146a/b prevented tumor cell proliferation and enhanced apoptosis. Functional analyses in vitro and in vivo revealed that FOXP3-induced miR-146a/b negatively regulate NF-κB activation by inhibiting the expression of IRAK1 and TRAF6. In chromatin immunoprecipitation assays, FOXP3 directly bound the promoter region of miR-146a but not of miR-146b, and FOXP3 interacted directly with NF-κB p65 to regulate an miR-146-NF-κB negative feedback regulation loop in normal breast epithelial and tumor cells, as demonstrated with luciferase reporter assays. Although FOXP3 significantly inhibited breast tumor growth and migration in vitro and metastasis in vivo, FOXP3-induced miR-146a/b contributed only to the inhibition of breast tumor growth. These data suggest that miR-146a/b contribute to FOXP3-mediated tumor suppression during tumor growth by triggering apoptosis. The identification of a FOXP3-miR-146-NF-κB axis provides an underlying mechanism for disruption of miR-146 family member expression and constitutive NF-κB activation in breast cancer cells. Linking the tumor suppressor function of FOXP3 to NF-κB activation reveals a potential therapeutic approach for cancers with FOXP3 defects. PMID:25712342

  6. 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. PMID:25641499

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

    SciTech Connect

    Zita, E.J.; Prager, S.C. . Plasma Physics Research); Ho, Y.L.; Schnack, D.D )

    1992-05-01

    MHD computation demonstrates that feedback can sustain reversal and reduce loop voltage in resistive-shell reversed field pinch (RFP) plasmas. Edge feedback on {approximately}2R/a tearing modes resonant near axis is found to restore plasma parameters to nearly their levels with a close-fitting conducting shell. When original dynamo modes are stabilized, neighboring tearing modes grow to maintain the RFP dynamo more efficiently. This suggests that experimentally observed limits on RFP pulselengths to the order of the shell time can be overcome by applying feedback to a few helical modes.

  8. Optical voltage reference

    DOEpatents

    Rankin, Richard; Kotter, Dale

    1994-01-01

    An optical voltage reference for providing an alternative to a battery source. The optical reference apparatus provides a temperature stable, high precision, isolated voltage reference through the use of optical isolation techniques to eliminate current and impedance coupling errors. Pulse rate frequency modulation is employed to eliminate errors in the optical transmission link while phase-lock feedback is employed to stabilize the frequency to voltage transfer function.

  9. Optical voltage reference

    DOEpatents

    Rankin, R.; Kotter, D.

    1994-04-26

    An optical voltage reference for providing an alternative to a battery source is described. The optical reference apparatus provides a temperature stable, high precision, isolated voltage reference through the use of optical isolation techniques to eliminate current and impedance coupling errors. Pulse rate frequency modulation is employed to eliminate errors in the optical transmission link while phase-lock feedback is employed to stabilize the frequency to voltage transfer function. 2 figures.

  10. 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

  11. 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.

  12. Global Feedback Simulator

    Energy Science and Technology Software Center (ESTSC)

    2015-10-29

    GFS is a simulation engine that is used for the characterization of Accelerator performance parameters based on the machine layout, configuration and noise sources. It combines extensively tested Feedback models with a longitudinal phase space tracking simulator along with the interaction between the two via beam-based feedback using a computationally efficient simulation engine. The models include beam instrumentation, considerations on loop delays for in both the R and beam-based feedback loops, as well as themore » ability to inject noise (both correlated and uncorrelated) at different points of the machine including a full characterization of the electron gun performance parameters.« less

  13. Frequency-Offset Cartesian Feedback Based on Polyphase Difference Amplifiers.

    PubMed

    Zanchi, Marta G; Pauly, John M; Scott, Greig C

    2010-05-01

    A modified Cartesian feedback method called "frequency-offset Cartesian feedback" and based on polyphase difference amplifiers is described that significantly reduces the problems associated with quadrature errors and DC-offsets in classic Cartesian feedback power amplifier control systems.In this method, the reference input and feedback signals are down-converted and compared at a low intermediate frequency (IF) instead of at DC. The polyphase difference amplifiers create a complex control bandwidth centered at this low IF, which is typically offset from DC by 200-1500 kHz. Consequently, the loop gain peak does not overlap DC where voltage offsets, drift, and local oscillator leakage create errors. Moreover, quadrature mismatch errors are significantly attenuated in the control bandwidth. Since the polyphase amplifiers selectively amplify the complex signals characterized by a +90° phase relationship representing positive frequency signals, the control system operates somewhat like single sideband (SSB) modulation. However, the approach still allows the same modulation bandwidth control as classic Cartesian feedback.In this paper, the behavior of the polyphase difference amplifier is described through both the results of simulations, based on a theoretical analysis of their architecture, and experiments. We then describe our first printed circuit board prototype of a frequency-offset Cartesian feedback transmitter and its performance in open and closed loop configuration. This approach should be especially useful in magnetic resonance imaging transmit array systems. PMID:20814450

  14. 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.

  15. Feedback control of waiting times.

    PubMed

    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. PMID:27176250

  16. Frequency-Offset Cartesian Feedback Based on Polyphase Difference Amplifiers

    PubMed Central

    Zanchi, Marta G.; Pauly, John M.; Scott, Greig C.

    2010-01-01

    A modified Cartesian feedback method called “frequency-offset Cartesian feedback” and based on polyphase difference amplifiers is described that significantly reduces the problems associated with quadrature errors and DC-offsets in classic Cartesian feedback power amplifier control systems. In this method, the reference input and feedback signals are down-converted and compared at a low intermediate frequency (IF) instead of at DC. The polyphase difference amplifiers create a complex control bandwidth centered at this low IF, which is typically offset from DC by 200–1500 kHz. Consequently, the loop gain peak does not overlap DC where voltage offsets, drift, and local oscillator leakage create errors. Moreover, quadrature mismatch errors are significantly attenuated in the control bandwidth. Since the polyphase amplifiers selectively amplify the complex signals characterized by a +90° phase relationship representing positive frequency signals, the control system operates somewhat like single sideband (SSB) modulation. However, the approach still allows the same modulation bandwidth control as classic Cartesian feedback. In this paper, the behavior of the polyphase difference amplifier is described through both the results of simulations, based on a theoretical analysis of their architecture, and experiments. We then describe our first printed circuit board prototype of a frequency-offset Cartesian feedback transmitter and its performance in open and closed loop configuration. This approach should be especially useful in magnetic resonance imaging transmit array systems. PMID:20814450

  17. Feedback: Theory and Accelerator Applications

    NASA Astrophysics Data System (ADS)

    Himel, T.

    The use of feedback to stabilize the beam and improve the performance of accelerators is becoming more common. The methods used to design the feedback algorithms are introduced and some practical implementation details are described. The design of a PID loop using classical control techniques is covered as is the design of an optimal controller using modern control theory. Some adaptive control techniques are also briefly described. Examples are given of multiple-input-multiple-output loops and of how to handle systems of many interacting feedback loops.

  18. Connective tissue growth factor (CCN2) and microRNA-21 are components of a positive feedback loop in pancreatic stellate cells (PSC) during chronic pancreatitis and are exported in PSC-derived exosomes.

    PubMed

    Charrier, Alyssa; Chen, Ruju; Chen, Li; Kemper, Sherri; Hattori, Takako; Takigawa, Masaharu; Brigstock, David R

    2014-06-01

    Pancreatitis is an inflammatory condition of the pancreas which, in its chronic form, involves tissue destruction, exocrine and endocrine insufficiency, increased risk of pancreatic cancer, and an extensive fibrotic pathology which is due to unrelenting collagen deposition by pancreatic stellate cells (PSC). In response to noxious agents such as alcohol-excessive consumption of which is a major cause of pancreatitis in the West-normally quiescent PSC undergo a phenotypic and functional transition to activated myofibroblasts which produce and deposit collagen at high levels. This process is regulated by connective tissue growth factor (CCN2), expression of which is highly up-regulated in activated PSC. We show that CCN2 production by activated PSC is associated with enhanced expression of microRNA-21 (miR-21) which was detected at high levels in activated PSC in a murine model of alcoholic chronic pancreatitis. A positive feedback loop between CCN2 and miR-21 was identified that resulted in enhancement of their respective expression as well as that of collagen α1(I). Both miR-21 and CCN2 mRNA were present in PSC-derived exosomes, which were characterized as 50-150 nm CD9-positive nano-vesicles. Exosomes from CCN2-GFP- or miR-21-GFP-transfected PSC were taken up by other PSC cultures, as shown by direct fluorescence or qRT-PCR for GFP. Collectively these studies establish miR-21 and CCN2 as participants in a positive feedback loop during PSC activation and as components of the molecular payload in PSC-derived exosomes that can be delivered to other PSC. Thus interactions between cellular or exosomal miR-21 and CCN2 represent novel aspects of fibrogenic regulation in PSC. Summary Chronic injury in the pancreas is associated with fibrotic pathology which is driven in large part by CCN2-dependent collagen production in pancreatic stellate cells. This study shows that CCN2 up-regulation in PSC is associated with increased expression of miR-21 which, in turn, is able to

  19. Acetylcholine Promotes Ca2+and NO-Oscillations in Adipocytes Implicating Ca2+→NO→cGMP→cADP-ribose→Ca2+ Positive Feedback Loop - Modulatory Effects of Norepinephrine and Atrial Natriuretic Peptide

    PubMed Central

    Turovsky, Egor A.; Turovskaya, Mariya V.; Dolgacheva, Ludmila P.; Zinchenko, Valery P.; Dynnik, Vladimir V.

    2013-01-01

    Purpose This study investigated possible mechanisms of autoregulation of Ca2+ signalling pathways in adipocytes responsible for Ca2+ and NO oscillations and switching phenomena promoted by acetylcholine (ACh), norepinephrine (NE) and atrial natriuretic peptide (ANP). Methods Fluorescent microscopy was used to detect changes in Ca2+ and NO in cultures of rodent white adipocytes. Agonists and inhibitors were applied to characterize the involvement of various enzymes and Ca2+-channels in Ca2+ signalling pathways. Results ACh activating M3-muscarinic receptors and Gβγ protein dependent phosphatidylinositol 3 kinase induces Ca2+ and NO oscillations in adipocytes. At low concentrations of ACh which are insufficient to induce oscillations, NE or α1, α2-adrenergic agonists act by amplifying the effect of ACh to promote Ca2+ oscillations or switching phenomena. SNAP, 8-Br-cAMP, NAD and ANP may also produce similar set of dynamic regimes. These regimes arise from activation of the ryanodine receptor (RyR) with the implication of a long positive feedback loop (PFL): Ca2+→ NO→cGMP→cADPR→Ca2+, which determines periodic or steady operation of a short PFL based on Ca2+-induced Ca2+ release via RyR by generating cADPR, a coagonist of Ca2+ at the RyR. Interplay between these two loops may be responsible for the observed effects. Several other PFLs, based on activation of endothelial nitric oxide synthase or of protein kinase B by Ca2+-dependent kinases, may reinforce functioning of main PFL and enhance reliability. All observed regimes are independent of operation of the phospholipase C/Ca2+-signalling axis, which may be switched off due to negative feedback arising from phosphorylation of the inositol-3-phosphate receptor by protein kinase G. Conclusions This study presents a kinetic model of Ca2+-signalling system operating in adipocytes and integrating signals from various agonists, which describes it as multivariable multi feedback network with a family of nested

  20. 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

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

    PubMed

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

    2012-01-01

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

  2. 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

  3. Theoretical Design of a Depolarized Interferometric Fiber-Optic Gyroscope (IFOG) on SMF-28 Single-Mode Standard Optical Fiber Based on Closed-Loop Sinusoidal Phase Modulation with Serrodyne Feedback Phase Modulation Using Simulation Tools for Tactical and Industrial Grade Applications.

    PubMed

    Pérez, Ramón José; Álvarez, Ignacio; Enguita, José María

    2016-01-01

    This article presents, by means of computational simulation tools, a full analysis and design of an Interferometric Fiber-Optic Gyroscope (IFOG) prototype based on a closed-loop configuration with sinusoidal bias phase- modulation. The complete design of the different blocks, optical and electronic, is presented, including some novelties as the sinusoidal bias phase-modulation and the use of an integrator to generate the serrodyne phase-modulation signal. The paper includes detailed calculation of most parameter values, and the plots of the resulting signals obtained from simulation tools. The design is focused in the use of a standard single-mode optical fiber, allowing a cost competitive implementation compared to commercial IFOG, at the expense of reduced sensitivity. The design contains an IFOG model that accomplishes tactical and industrial grade applications (sensitivity ≤ 0.055 °/h). This design presents two important properties: (1) an optical subsystem with advanced conception: depolarization of the optical wave by means of Lyot depolarizers, which allows to use a sensing coil made by standard optical fiber, instead by polarization maintaining fiber, which supposes consequent cost savings and (2) a novel and simple electronic design that incorporates a linear analog integrator with reset in feedback chain, this integrator generating a serrodyne voltage-wave to apply to Phase-Modulator (PM), so that it will be obtained the interferometric phase cancellation. This particular feedback design with sawtooth-wave generated signal for a closed-loop configuration with sinusoidal bias phase modulation has not been reported till now in the scientific literature and supposes a considerable simplification with regard to previous designs based on similar configurations. The sensing coil consists of an 8 cm average diameter spool that contains 300 m of standard single-mode optical-fiber (SMF-28 type) realized by quadrupolar winding. The working wavelength will be

  4. 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. PMID:26456277

  5. A synthetic gene circuit for measuring autoregulatory feedback control.

    PubMed

    Schikora-Tamarit, Miquel Àngel; Toscano-Ochoa, Carlos; Domingo Espinós, Júlia; Espinar, Lorena; Carey, Lucas B

    2016-04-18

    Autoregulatory feedback loops occur in the regulation of molecules ranging from ATP to MAP kinases to zinc. Negative feedback loops can increase a system's robustness, while positive feedback loops can mediate transitions between cell states. Recent genome-wide experimental and computational studies predict hundreds of novel feedback loops. However, not all physical interactions are regulatory, and many experimental methods cannot detect self-interactions. Our understanding of regulatory feedback loops is therefore hampered by the lack of high-throughput methods to experimentally quantify the presence, strength and temporal dynamics of autoregulatory feedback loops. Here we present a mathematical and experimental framework for high-throughput quantification of feedback regulation and apply it to RNA binding proteins (RBPs) in yeast. Our method is able to determine the existence of both direct and indirect positive and negative feedback loops, and to quantify the strength of these loops. We experimentally validate our model using two RBPs which lack native feedback loops and by the introduction of synthetic feedback loops. We find that RBP Puf3 does not natively participate in any direct or indirect feedback regulation, but that replacing the native 3'UTR with that of COX17 generates an auto-regulatory negative feedback loop which reduces gene expression noise. Likewise, RBP Pub1 does not natively participate in any feedback loops, but a synthetic positive feedback loop involving Pub1 results in increased expression noise. Our results demonstrate a synthetic experimental system for quantifying the existence and strength of feedback loops using a combination of high-throughput experiments and mathematical modeling. This system will be of great use in measuring auto-regulatory feedback by RNA binding proteins, a regulatory motif that is difficult to quantify using existing high-throughput methods. PMID:26728081

  6. 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.

  7. Voltage-Controlled Oscillator

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Integrated Component Systems, Inc. incorporated information from a NASA Tech Briefs article into a voltage-controlled oscillator it designed for a customer. The company then applied the technology to its series of phase-locked loop synthesizers, which offer superior phase noise performance.

  8. 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…

  9. 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

  10. Open-loop Band excitation Kelvin Probe Force Microscopy

    SciTech Connect

    Guo, Senli; Kalinin, Sergei V; Jesse, Stephen

    2012-01-01

    A multidimensional scanning probe microscopy approach for quantitative, cross-talk free mapping of surface electrostatic properties is demonstrated. Open-loop band excitation Kelvin probe force microscopy (OL BE KPFM) probes the full response-frequency-potential surface at each pixel at standard imaging rates. The subsequent analysis reconstructs work function, tip surface capacitance gradient and resonant frequency maps, obviating feedback-related artifacts. OL BE KPFM imaging is demonstrated for several materials systems with topographic, potential and combined contrast. This approach combines the features of both frequency and amplitude KPFM and allows complete decoupling of topographic and voltage contributions to the KPFM signal.

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

    PubMed Central

    Singh, Raghvendra

    2016-01-01

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

  12. 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…

  13. 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.

  14. E-beam high voltage switching power supply

    DOEpatents

    Shimer, Daniel W.; Lange, Arnold C.

    1997-01-01

    A high power, solid state power supply is described for producing a controllable, constant high voltage output under varying and arcing loads suitable for powering an electron beam gun or other ion source. The present power supply is most useful for outputs in a range of about 100-400 kW or more. The power supply is comprised of a plurality of discrete switching type dc-dc converter modules, each comprising a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, and an output rectifier for producing a dc voltage at the output of each module. The inputs to the converter modules are fed from a common dc rectifier/filter and are linked together in parallel through decoupling networks to suppress high frequency input interactions. The outputs of the converter modules are linked together in series and connected to the input of the transmission line to the load through a decoupling and line matching network. The dc-dc converter modules are phase activated such that for n modules, each module is activated equally 360.degree./n out of phase with respect to a successive module. The phased activation of the converter modules, combined with the square current waveforms out of the step up transformers, allows the power supply to operate with greatly reduced output capacitance values which minimizes the stored energy available for discharge into an electron beam gun or the like during arcing. The present power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle using simulated voltage feedback signals and voltage feedback loops. Circuitry is also provided for sensing incipient arc currents reflected at the output of the power supply and for simultaneously decoupling the power supply circuitry from the arcing load.

  15. E-beam high voltage switching power supply

    DOEpatents

    Shimer, D.W.; Lange, A.C.

    1997-03-11

    A high power, solid state power supply is described for producing a controllable, constant high voltage output under varying and arcing loads suitable for powering an electron beam gun or other ion source. The present power supply is most useful for outputs in a range of about 100-400 kW or more. The power supply is comprised of a plurality of discrete switching type dc-dc converter modules, each comprising a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, and an output rectifier for producing a dc voltage at the output of each module. The inputs to the converter modules are fed from a common dc rectifier/filter and are linked together in parallel through decoupling networks to suppress high frequency input interactions. The outputs of the converter modules are linked together in series and connected to the input of the transmission line to the load through a decoupling and line matching network. The dc-dc converter modules are phase activated such that for n modules, each module is activated equally 360{degree}/n out of phase with respect to a successive module. The phased activation of the converter modules, combined with the square current waveforms out of the step up transformers, allows the power supply to operate with greatly reduced output capacitance values which minimizes the stored energy available for discharge into an electron beam gun or the like during arcing. The present power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle using simulated voltage feedback signals and voltage feedback loops. Circuitry is also provided for sensing incipient arc currents reflected at the output of the power supply and for simultaneously decoupling the power supply circuitry from the arcing load. 7 figs.

  16. IFN-λ Inhibits MiR-122 Transcription through a Stat3-HNF4α Inflammatory Feedback Loop in an IFN-α Resistant HCV Cell Culture System

    PubMed Central

    Aboulnasr, Fatma; Hazari, Sidhartha; Nayak, Satyam; Chandra, Partha K.; Panigrahi, Rajesh; Ferraris, Pauline; Chava, Srinivas; Kurt, Ramazan; Song, Kyongsub; Dash, Asha; Balart, Luis A.; Garry, Robert F.; Wu, Tong; Dash, Srikanta

    2015-01-01

    Background HCV replication in persistently infected cell culture remains resistant to IFN-α/RBV combination treatment, whereas IFN-λ1 induces viral clearance. The antiviral mechanisms by which IFN-λ1 induces sustained HCV clearance have not been determined. Aim To investigate the mechanisms by which IFN-λ clears HCV replication in an HCV cell culture model. Methods IFN-α sensitive (S3-GFP) and resistant (R4-GFP) cells were treated with equivalent concentrations of either IFN-α or IFN-λ. The relative antiviral effects of IFN-α and IFN-λ1 were compared by measuring the HCV replication, quantification of HCV-GFP expression by flow cytometry, and viral RNA levels by real time RT-PCR. Activation of Jak-Stat signaling, interferon stimulated gene (ISG) expression, and miRNA-122 transcription in S3-GFP and R4-GFP cells were examined. Results We have shown that IFN-λ1 induces HCV clearance in IFN-α resistant and sensitive replicon cell lines in a dose dependent manner through Jak-Stat signaling, and induces STAT 1 and STAT 2 activation, ISRE-luciferase promoter activation and ISG expression. Stat 3 activation is also involved in IFN-λ1 induced antiviral activity in HCV cell culture. IFN-λ1 induced Stat 3 phosphorylation reduces the expression of hepatocyte nuclear factor 4 alpha (HNF4α) through miR-24 in R4-GFP cells. Reduced expression of HNF4α is associated with decreased expression of miR-122 resulting in an anti-HCV effect. Northern blot analysis confirms that IFN-λ1 reduces miR-122 levels in R4-GFP cells. Our results indicate that IFN-λ1 activates the Stat 3-HNF4α feedback inflammatory loop to inhibit miR-122 transcription in HCV cell culture. Conclusions In addition to the classical Jak–Stat antiviral signaling pathway, IFN-λ1 inhibits HCV replication through the suppression of miRNA-122 transcription via an inflammatory Stat 3–HNF4α feedback loop. Inflammatory feedback circuits activated by IFNs during chronic inflammation expose non

  17. Regulation of BRAF protein stability by a negative feedback loop involving the MEK-ERK pathway but not the FBXW7 tumour suppressor.

    PubMed

    Hernandez, Maria Aguilar; Patel, Bipin; Hey, Fiona; Giblett, Susan; Davis, Hayley; Pritchard, Catrin

    2016-06-01

    The (V600E)BRAF oncogenic mutation is detected in a wide range of human cancers and induces hyperactivation of the downstream MEK-ERK signalling cascade. Although output of the BRAF-MEK-ERK pathway is regulated by feed-forward RAF activity, feedback control also plays an important role. One such feedback pathway has been identified in Caenorhabditis elegans and involves ERK-mediated phosphorylation of BRAF within a CDC4 phosphodegron (CPD), targeting BRAF for degradation via CDC4 (also known as FBXW7), a component of the SKP1/CUL1/F-box (SCF) E3 ubiquitin ligase complex. Here we investigate this pathway in mammalian cells. Short-term expression of autochthonous (V600E)BRAF in mouse embryonic fibroblasts (MEFs) leads to down-regulation of BRAF protein levels in a proteasome-dependent manner and (V600E)BRAF has a reduced half-life compared to (WT)BRAF in HEK293(T) cells. These effects were reversed by treatment with the MEK inhibitor PD184352. We have identified the equivalent CPD at residues 400-405 in human BRAF and have found that mutation of ERK phosphorylation sites at residues T401 and S405 in (V600E)BRAF increases the half-life of the protein. While BRAF and FBXW7 co-immunoprecipitated, the overexpression of FBXW7 did not influence the half-life of either (WT)BRAF or (V600E)BRAF. Furthermore, disruption of the substrate-binding site of mouse FBXW7 using the R482Q mutation did not affect the interaction with BRAF and the expression levels of (WT)BRAF and (V600E)BRAF were not altered in MEFs derived from mice with the homozygous knockin (R482Q)FBXW7 mutation. Overall these data confirm the existence of a negative feedback pathway by which BRAF protein stability is regulated by ERK. However, unlike the situation in C. elegans, FBXW7 does not play a unique role in mediating subsequent BRAF degradation. PMID:26898828

  18. The dc-to-dc converters employing staggered-phase power switches with two-loop control

    NASA Technical Reports Server (NTRS)

    Wester, G. W. (Inventor)

    1976-01-01

    A switched inductor voltage is coupled to a sense winding in each phase, and all sense windings are connected in series to one of two feedback loops to provide a signal that indicates when one of the power switches is on as the principal determinant of switching instants. A sequencer is triggered each time a pulse generator is triggered to turn on a different power switch in sequence at each switching instant.

  19. The Perceptual Characteristics of Voice-Hallucinations in Deaf People: Insights into the Nature of Subvocal Thought and Sensory Feedback Loops

    PubMed Central

    Atkinson, Joanna R.

    2006-01-01

    The study of voice-hallucinations in deaf individuals, who exploit the visuomotor rather than auditory modality for communication, provides rare insight into the relationship between sensory experience and how “voices” are perceived. Relatively little is known about the perceptual characteristics of voice-hallucinations in congenitally deaf people who use lip-reading or sign language as their preferred means of communication. The existing literature on hallucinations in deaf people is reviewed, alongside consideration of how such phenomena may fit into explanatory subvocal articulation hypotheses proposed for auditory verbal hallucinations in hearing people. It is suggested that a failure in subvocal articulation processes may account for voice-hallucinations in both hearing and deaf people but that the distinct way in which hallucinations are experienced may be due to differences in a sensory feedback component, which is influenced by both auditory deprivation and language modality. This article highlights how the study of deaf people may inform wider understanding of auditory verbal hallucinations and subvocal processes generally. PMID:16510696

  20. 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.}

  1. Hsa-mir-145 is the top EWS-FLI1 repressed microRNA involved in a positive feed-back loop in Ewing’s sarcoma

    PubMed Central

    Ban, Jozef; Jug, Gunhild; Mestdagh, Pieter; Schwentner, Raphaela; Kauer, Max; Aryee, Dave N.T.; Schaefer, Karl-Ludwig; Nakatani, Fumihiko; Scotlandi, Katia; Reiter, Marlies; Strunk, Dirk; Speleman, Frank; Vandesompele, Jo; Kovar, Heinrich

    2016-01-01

    EWS-FLI1 is a chromosome translocation-derived chimeric transcription factor that plays a central and rate-limiting role in the pathogenesis of Ewing’s sarcoma. While the EWS-FLI1 transcriptomic signature has been extensively characterized on the mRNA level, information on its impact on non-coding RNA expression is lacking. We have performed a genome-wide analysis of microRNAs affected by RNAi-mediated silencing of EWS-FLI1 in Ewing’s sarcoma cell lines and differentially expressed between primary Ewing’s sarcoma and mesenchymal progenitor cells. Here, we report on the identification of hsa-mir-145 as the top EWS-FLI1 repressed microRNA. Upon knockdown of EWS-FLI1, hsa-mir-145 expression dramatically increases in all Ewing’s sarcoma cell lines tested. Vice versa, ectopic expression of the microRNA in Ewing’s sarcoma cell lines strongly reduced EWS-FLI1 protein, while transfection of an anti-mir to hsa-mir-145 increased EWS-FLI1 levels. Reporter gene assays revealed that this modulation of EWS-FLI1 protein was mediated by the microRNA targeting the FLI1 3’UTR. Mutual regulation of EWS-FLI1 and hsa-mir-145 was mirrored by an inverse correlation between their expression levels in 4 Ewing’s sarcoma cell lines tested. Consistent with the role of EWS-FLI1 in Ewing’s sarcoma growth regulation, forced hsa-mir-145 expression halted Ewing’s sarcoma cell line growth. These results identify feed-back regulation between EWS-FLI1 and hsa-mir-145 as an important component of EWS-FLI1 mediated Ewing’s sarcomagenesis that may open a new avenue to future microRNA-mediated therapy of this devastating malignant disease. PMID:21217773

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

    PubMed Central

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

    2016-01-01

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

  3. STABILITY OF HIGH VOLTAGE MODULATORS FOR NONLINEAR LOADS

    SciTech Connect

    PAWLEY,J.C; TOOKER,J; PEAVY,J; CARY,W.P; NEREM,A; HOYT,D; LOHR,J

    2003-10-01

    OAK-B135 Gyrotrons have a nonlinear voltage--current characteristic such that the small signal or ac impedance changes as operational voltage and currents are reached. The ac impedance determines the stability of a voltage or current control system. this can become particularly challenging when several gyrotron are connected in parallel to a single modulator. With all gyrotrons hooked to a common ground, large current loops can be generated as well as non-canceling currents in individual coaxial lines. These inequalities can provide the required feedback impulse to start an oscillation condition in the power system for the tubes. Recent operation of two CPI 110 GHz gyrotrons in the MN class from a single modulator on DIII-D has shown instability in the power system. An oscillation in the drive current occurs at various points in the ramp up and flat top portions of the 80 kV voltage pulse with each tube drawing 40 A at full voltage. Efforts to stabilize these instabilities are presented along with some modeling and examination of the issues for gyrotron modulators.

  4. Finite Feedback Cycling in Structural Equation Models

    ERIC Educational Resources Information Center

    Hayduk, Leslie A.

    2009-01-01

    In models containing reciprocal effects, or longer causal loops, the usual effect estimates assume that any effect touching a loop initiates an infinite cycling of effects around that loop. The real world, in contrast, might permit only finite feedback cycles. I use a simple hypothetical model to demonstrate that if the world permits only a few…

  5. 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.

  6. Voltage regulator

    SciTech Connect

    Rossetti, N.

    1986-12-09

    This patent describes a prior art integrated circuit voltage regulator having an unregulated voltage input terminal and a regulated voltage output terminal, and further comprising: a first transistor having an emitter, a collector and a base, the first transistor having a first base-emitter voltage characteristic, the collector of the first transistor being connected through a first resistor to a current source. The current source is derived from the unregulated voltage, the emitter of the first transistor being connected through a second resistor to a reference voltage; and a second transistor having an emitter, a collector and a base, the second transistor having a second base-emitter voltage characteristic, the base of the second transistor being connected to the collector of the first transistor. The collector of the second transistor is connected to the current source, the emitter of the second transistor being connected to the reference voltage. The regulated output of the voltage regulator is provided at the collector of the second transistor and the regulated voltage output is a function of the first base-emitter voltage characteristic of the first transistor plus the quantity comprising the difference between the first base-emitter voltage characteristic of the first transistor and the second base-emitter voltage characteristic of the second transistor, times the ratio of the value of resistance of the first resistor and the value of resistance of the second resistor. The improvement described here comprises: a third transistor having a collector, an emitter and a base.

  7. 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

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

    PubMed

    Zhao, Mengyang; Luo, Rongcheng; Liu, Yiyi; Gao, Linyuan; Fu, Zhaojian; Fu, Qiaofen; Luo, Xiaojun; Chen, Yiyu; Deng, Xiaojie; Liang, Zixi; Li, Xin; Cheng, Chao; Liu, Zhen; Fang, Weiyi

    2016-01-01

    The biological role of miR-3188 has not yet been reported in the context of cancer. In this study, we observe that miR-3188 not only reduces cell-cycle transition and proliferation, but also significantly prolongs the survival time of tumour-bearing mice as well as sensitizes cells to 5-FU. Mechanistic analyses indicate that miR-3188 directly targets mTOR to inactivate p-PI3K/p-AKT/c-JUN and induces its own expression. This feedback loop further suppresses cell-cycle signalling through the p-PI3K/p-AKT/p-mTOR pathway. Interestingly, we also observe that miR-3188 direct targeting of mTOR is mediated by FOXO1 suppression of p-PI3K/p-AKT/c-JUN signalling. In clinical samples, reduced miR-3188 is an unfavourable factor and negatively correlates with mTOR and c-JUN levels but positively correlates with FOXO1 expression. Our studies demonstrate that as a tumour suppressor, miR-3188 directly targets mTOR to stimulate its own expression and participates in FOXO1-mediated repression of cell growth, tumorigenesis and NPC chemotherapy resistance. PMID:27095304

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

    PubMed Central

    Zhao, Mengyang; Luo, Rongcheng; Liu, Yiyi; Gao, Linyuan; Fu, Zhaojian; Fu, Qiaofen; Luo, Xiaojun; Chen, Yiyu; Deng, Xiaojie; Liang, Zixi; Li, Xin; Cheng, Chao; Liu, Zhen; Fang, Weiyi

    2016-01-01

    The biological role of miR-3188 has not yet been reported in the context of cancer. In this study, we observe that miR-3188 not only reduces cell-cycle transition and proliferation, but also significantly prolongs the survival time of tumour-bearing mice as well as sensitizes cells to 5-FU. Mechanistic analyses indicate that miR-3188 directly targets mTOR to inactivate p-PI3K/p-AKT/c-JUN and induces its own expression. This feedback loop further suppresses cell-cycle signalling through the p-PI3K/p-AKT/p-mTOR pathway. Interestingly, we also observe that miR-3188 direct targeting of mTOR is mediated by FOXO1 suppression of p-PI3K/p-AKT/c-JUN signalling. In clinical samples, reduced miR-3188 is an unfavourable factor and negatively correlates with mTOR and c-JUN levels but positively correlates with FOXO1 expression. Our studies demonstrate that as a tumour suppressor, miR-3188 directly targets mTOR to stimulate its own expression and participates in FOXO1-mediated repression of cell growth, tumorigenesis and NPC chemotherapy resistance. PMID:27095304

  10. 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.

  11. Feedback oscillator functions as low-level pulse stretcher

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Low trigger pulses of the pulse stretcher circuit are obtained by forward biasing the transistor oscillator. The loop gain is kept below unity and prevents free-running oscillation. Two parallel feedback loops improve the stretching capabilities.

  12. Feedback cooling of currents

    NASA Astrophysics Data System (ADS)

    Washburn, Sean

    1989-02-01

    Just as feedback can be used to correct errors in the output voltages of amplifiers, it can also be used to remove noise from the current through a resistor. Such a feedback amplifier behaves as a refrigerator cooling the electrons in a resistor connnected to it. This principle has been recognized since the 1940s but has been largely ignored because the cooling power available from such refrigerators is miniscule. It is pointed out here that the method might be practical for cooling the currents in the microscopic circuits that are typical of modern electrical engineering and recent studies in transport physics.

  13. 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.

  14. 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.

  15. Interactive Information Seeking and Retrieving: A Third Feedback Framework.

    ERIC Educational Resources Information Center

    Spink, Amanda

    1996-01-01

    Presents an overview of feedback within the cybernetics and social frameworks. These feedback concepts are then compared with the interactive feedback concept evolving within the framework of information seeking and retrieving, based on their conceptualization of the feedback loop and notion of information. (Author/AEF)

  16. A double feedback loop mediated by microRNA-23a/27a/24-2 regulates M1 versus M2 macrophage polarization and thus regulates cancer progression

    PubMed Central

    Ma, Sisi; Liu, Min; Xu, Zhenbiao; Li, Yanshuang; Guo, Hui; Ge, Yehua; Liu, Yanxin; Zheng, Dexian; Shi, Juan

    2016-01-01

    In response to microenvironmental signals, macrophages undergo different types of activation, including the “classic” pro-inflammatory phenotype (also called M1) and the “alternative” anti-inflammatory phenotype (also called M2). Macrophage polarized activation has profound effects on immune and inflammatory responses, but mechanisms underlying the various types of macrophage is still in its infancy. In this study, we reported that M1-type stimulation could down-regulate miR-23a/27a/24-2 cluster transcription through the binding of NF-κB to this cluster's promoter and that miR-23a in turn activated the NF-κB pathway by targeting A20 and thus promoted the production of pro-inflammatory cytokines. Furthermore, STAT6 occupied the miR-23a/27a/24-2 cluster promoter and activated their transcription in IL-4-stimulated macrophages. In addition, miR-23a in turn suppressed the JAK1/STAT-6 pathway and reduced the production of M2 type cytokines by targeting JAK1 and STAT-6 directly, while miR-27a showed the same phenotype by targeting IRF4 and PPAR-γ. The miR-23a/27a/24-2 cluster was shown to be significantly decreased in TAMs of breast cancer patients, and macrophages overexpressing the miR-23a/27a/24-2 cluster inhibited tumor growth in vivo. Taken together, these data integrated microRNA expression and function into macrophage polarization networks and identified a double feedback loop consisting of the miR-23a/27a/24-2 cluster and the key regulators of the M1 and M2 macrophage polarization pathway. Moreover, miR-23a/27a/24-2 regulates the polarization of tumor-associated macrophages and thus promotes cancer progression. PMID:26540574

  17. A double feedback loop mediated by microRNA-23a/27a/24-2 regulates M1 versus M2 macrophage polarization and thus regulates cancer progression.

    PubMed

    Ma, Sisi; Liu, Min; Xu, Zhenbiao; Li, Yanshuang; Guo, Hui; Ge, Yehua; Liu, Yanxin; Zheng, Dexian; Shi, Juan

    2016-03-22

    In response to microenvironmental signals, macrophages undergo different types of activation, including the "classic" pro-inflammatory phenotype (also called M1) and the "alternative" anti-inflammatory phenotype (also called M2). Macrophage polarized activation has profound effects on immune and inflammatory responses, but mechanisms underlying the various types of macrophage is still in its infancy. In this study, we reported that M1-type stimulation could down-regulate miR-23a/27a/24-2 cluster transcription through the binding of NF-κB to this cluster's promoter and that miR-23a in turn activated the NF-κB pathway by targeting A20 and thus promoted the production of pro-inflammatory cytokines. Furthermore, STAT6 occupied the miR-23a/27a/24-2 cluster promoter and activated their transcription in IL-4-stimulated macrophages. In addition, miR-23a in turn suppressed the JAK1/STAT-6 pathway and reduced the production of M2 type cytokines by targeting JAK1 and STAT-6 directly, while miR-27a showed the same phenotype by targeting IRF4 and PPAR-γ. The miR-23a/27a/24-2 cluster was shown to be significantly decreased in TAMs of breast cancer patients, and macrophages overexpressing the miR-23a/27a/24-2 cluster inhibited tumor growth in vivo. Taken together, these data integrated microRNA expression and function into macrophage polarization networks and identified a double feedback loop consisting of the miR-23a/27a/24-2 cluster and the key regulators of the M1 and M2 macrophage polarization pathway. Moreover, miR-23a/27a/24-2 regulates the polarization of tumor-associated macrophages and thus promotes cancer progression. PMID:26540574

  18. VOLTAGE REGULATOR

    DOEpatents

    Von Eschen, R.L.; Scheele, P.F.

    1962-04-24

    A transistorized voltage regulator which provides very close voitage regulation up to about 180 deg F is described. A diode in the positive line provides a constant voltage drop from the input to a regulating transistor emitter. An amplifier is coupled to the positive line through a resistor and is connected between a difference circuit and the regulating transistor base which is negative due to the difference in voltage drop across thc diode and the resistor so that a change in the regulator output causes the amplifier to increase or decrease the base voltage and current and incrcase or decrease the transistor impedance to return the regulator output to normal. (AEC)

  19. Modular high voltage power supply for chemical analysis

    DOEpatents

    Stamps, James F.; Yee, Daniel D.

    2010-05-04

    A high voltage power supply for use in a system such as a microfluidics system, uses a DC-DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC-DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

  20. Modular high voltage power supply for chemical analysis

    DOEpatents

    Stamps, James F.; Yee, Daniel D.

    2008-07-15

    A high voltage power supply for use in a system such as a microfluidics system, uses a DC-DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC-DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

  1. Modular high voltage power supply for chemical analysis

    DOEpatents

    Stamps, James F.; Yee, Daniel D.

    2007-01-09

    A high voltage power supply for use in a system such as a microfluidics system, uses a DC--DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC--DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

  2. RF feedback development for the PEP-II B Factory

    SciTech Connect

    Corredoura, P.; Sapozhnikov, L.; Tighe, R.

    1994-06-01

    In PEP-II heavy beam loading along with a relatively long revolution period combine to strongly drive lower coupled-bunch modes through interaction with the fundamental cavity mode. Feedback techniques can be applied to reduce the cavity impedance seen by the beam. Several RF feedback loops are planned to reduce the growth rates down to a level which can be damped by the relatively low power bunch-by-bunch longitudinal feedback system. This paper describes the RF feedback loops as well as hardware tests using a 500 kW klystron, analog and digital feedback loops, and a low power test cavity.

  3. TUNE FEEDBACK AT RHIC

    SciTech Connect

    CAMERON,P.; CERNIGLIA,P.; CONNOLLY,R.; CUPOLO,J.; DAWSON,W.C.; DEGEN,C.; DELLAPENNA,A.; DELONG,J.; DREES,A.; HUHN,A.; KESSELMAN,M.; MARUSIC,A.; OERTER,B.; MEAD,J.; SCHULTHEISS,C.; SIKORA,R.; VAN ZEIJTS,J.

    2001-06-18

    Preliminary phase-locked loop betatron tune measurement results were obtained during RHIC 2000 with a resonant Beam Position Monitor. These results suggested the possibility of incorporating PLL tune measurement into a tune feedback system for RHIC 2001. Tune feedback is useful in a superconducting accelerator, where the machine cycle time is long and inefficient acceleration due to resonance crossing is not comfortably tolerated. This is particularly true with the higher beam intensities planned for RHIC 2001. We present descriptions of a PLL tune measurement system implemented in the DSP/FPGA environment of a RHIC BPM electronics module and the feedback system into which the measurement is incorporated to regulate tune. In addition, we present results from the commissioning of this system during RHIC 2001.

  4. Power-MOSFET Voltage Regulator

    NASA Technical Reports Server (NTRS)

    Miller, W. N.; Gray, O. E.

    1982-01-01

    Ninety-six parallel MOSFET devices with two-stage feedback circuit form a high-current dc voltage regulator that also acts as fully-on solid-state switch when fuel-cell out-put falls below regulated voltage. Ripple voltage is less than 20 mV, transient recovery time is less than 50 ms. Parallel MOSFET's act as high-current dc regulator and switch. Regulator can be used wherever large direct currents must be controlled. Can be applied to inverters, industrial furnaces photovoltaic solar generators, dc motors, and electric autos.

  5. STABILIZED FEEDBACK AMPLIFIER

    DOEpatents

    Fishbine, H.L.; Sewell, C. Jr.

    1957-08-01

    Negative feedback amplifiers, and particularly a negative feedback circuit which is economical on amode power consumption, are described. Basically, the disclosed circuit comprises two tetrode tubes where the output of the first tube is capacitamce coupled to the grid of the second tube, which in turn has its plate coupled to the cathode of the first tube to form a degenerative feedback circuit. Operating potential for screen of the second tube is supplied by connecting the cathode resistor of the first tube to the screen, while the screen is by-passed to the cathode of its tube for the amplified frequencies. Also, the amplifier incorporates a circuit to stabilize the transconductance of the tubes by making the grid potential of each tube interdependent on anode currents of both lubes by voltage divider circuitry.

  6. Computer automation for feedback system design

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Mathematical techniques and explanations of various steps used by an automated computer program to design feedback systems are summarized. Special attention was given to refining the automatic evaluation suboptimal loop transmission and the translation of time to frequency domain specifications.

  7. Digital-voltage curve generator

    NASA Technical Reports Server (NTRS)

    Perlman, M.

    1970-01-01

    Curve generator capable of producing precisely repeatable curve for any single-valued function of voltage versus time uses digital approach, implemented by means of clocked feedback shift register, large scale integrated circuit diode matrix comprising about 12,000 diodes, counter, and digital-to-analog converter.

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

    PubMed Central

    Nandi, Rabindranath; Pattanayak, Sandhya; Das, Sagarika

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  10. Phase loop bandwidth measurements on the advanced photon source 352 MHz rf systems

    SciTech Connect

    Horan, D.; Nassiri, A.; Schwartz, C.

    1997-08-01

    Phase loop bandwidth tests were performed on the Advanced Photon Source storage ring 352-MHz rf systems. These measurements were made using the HP3563A Control Systems Analyzer, with the rf systems running at 30 kilowatts into each of the storage ring cavities, without stored beam. An electronic phase shifter was used to inject approximately 14 degrees of stimulated phase shift into the low-level rf system, which produced measureable response voltage in the feedback loops without upsetting normal rf system operation. With the PID (proportional-integral-differential) amplifier settings at the values used during accelerator operation, the measurement data revealed that the 3-dB response for the cavity sum and klystron power-phase loops is approximately 7 kHz and 45 kHz, respectively, with the cavities the primary bandwidth-limiting factor in the cavity-sum loop. Data were taken at various PID settings until the loops became unstable. Crosstalk between the two phase loops was measured.

  11. Pepper CabZIP63 acts as a positive regulator during Ralstonia solanacearum or high temperature-high humidity challenge in a positive feedback loop with CaWRKY40.

    PubMed

    Shen, Lei; Liu, Zhiqin; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Lin, Wei; Wang, Rongzhang; Yu, Huanxin; Mou, Shaoliang; Hussain, Ansar; Cheng, Wei; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-04-01

    CaWRKY40 is known to act as a positive regulator in the response of pepper (Capsicum annuum) to Ralstonia solanacearum inoculation (RSI) or high temperature-high humidity (HTHH), but the underlying mechanism remains elusive. Herein, we report that CabZIP63, a pepper bZIP family member, participates in this process by regulating the expression of CaWRKY40. CabZIP63 was found to localize in the nuclei, be up-regulated by RSI or HTHH, bind to promoters of both CabZIP63(pCabZIP63) and CaWRKY40(pCaWRKY40), and activate pCabZIP63- and pCaWRKY40-driven β-glucuronidase expression in a C- or G-box-dependent manner. Silencing of CabZIP63 by virus-induced gene silencing (VIGS) in pepper plants significantly attenuated their resistance to RSI and tolerance to HTHH, accompanied by down-regulation of immunity- or thermotolerance-associated CaPR1, CaNPR1, CaDEF1, and CaHSP24. Hypersensitive response-mediated cell death and expression of the tested immunity- and thermotolerance-associated marker genes were induced by transient overexpression (TOE) of CabZIP63, but decreased by that of CabZIP63-SRDX. Additionally, binding of CabZIP63 to pCaWRKY40 was up-regulated by RSI or HTHH, and the transcript level of CaWRKY40 and binding of CaWRKY40 to the promoters of CaPR1, CaNPR1, CaDEF1 and CaHSP24 were up-regulated by TOE of CabZIP63. On the other hand, CabZIP63 was also up-regulated transcriptionally by TOE of CaWRKY40. The data suggest collectively that CabZIP63 directly or indirectly regulates the expression of CaWRKY40 at both the transcriptional and post-transcriptional level, forming a positive feedback loop with CaWRKY40 during pepper's response to RSI or HTHH. Altogether, our data will help to elucidate the underlying mechanism of crosstalk between pepper's response to RSI and HTHH. PMID:26936828

  12. Pepper CabZIP63 acts as a positive regulator during Ralstonia solanacearum or high temperature–high humidity challenge in a positive feedback loop with CaWRKY40

    PubMed 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

  13. 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.

  14. Feedback control of pulsed laser deposition processes

    NASA Astrophysics Data System (ADS)

    Laube, S. J. P.; Stark, E. F.

    1993-10-01

    Implementation of closed loop feedback on PLD (pulsed laser deposition) requires actuators and sensors. Improvements in quality and reproducibility of material depositions are achieved by actuating the process towards desired operating regions. Empirical relationships are experimentally determined for describing the complex dynamical interactions of laser parameters. Feedback control based on this description can then be implemented to reduce process disorder.

  15. Architecture for a High-to-Medium-Voltage Power Converter

    NASA Technical Reports Server (NTRS)

    Vorpenian, Vatche

    2008-01-01

    A power converter now undergoing development is required to operate at a DC input potential ranging between 5.5 and 10 kV and a DC output potential of 400 V at a current up to 25 A. This power converter is also required to be sufficiently compact and reliable to fit and operate within the confines of a high-pressure case to be lowered to several miles (approx.5 km) below the surface of the ocean. The architecture chosen to satisfy these requirements calls for a series/ parallel arrangement of 48 high-frequency, pulse-width-modulation (PWM), transformer-isolation DC-to-DC power converter blocks. The input sides of the converter blocks would be connected in series so that the input potential would be divided among them, each of them being exposed to an input potential of no more than 10 kV/48 . 210 V. The series connection of inputs would also enforce a requirement that all the converter blocks operate at the same input current. The outputs of the converter blocks would be connected in a matrix comprising 6 parallel legs, each leg being a cascade of eight outputs wired in series (see figure). All the converter blocks would be identical within the tolerances of the values of their components. A single voltage feedback loop would regulate the output potential. All the converter blocks would be driven by the same PWM waveform generated by this feedback loop. The power transformer of each converter block would have a unity turns ratio and would be capable of withstanding as much as 10 kVDC between its primary and secondary windings. (Although, in general, the turns ratio could be different from unity, the simplest construction for minimizing leakage and maximizing breakdown voltage is attained at a turns ratio of unity.)

  16. Self-organization of pulsing and bursting in a CO2 laser with opto-electronic feedback.

    PubMed

    Freire, Joana G; Meucci, Riccardo; Arecchi, Fortunato Tito; Gallas, Jason A C

    2015-09-01

    We report a detailed investigation of the stability of a CO2 laser with feedback as described by a six-dimensional rate-equations model which provides satisfactory agreement between numerical and experimental results. We focus on experimentally accessible parameters, like bias voltage, feedback gain, and the bandwidth of the feedback loop. The impact of decay rates and parameters controlling cavity losses are also investigated as well as control planes which imply changes of the laser physical medium. For several parameter combinations, we report stability diagrams detailing how laser spiking and bursting is organized over extended intervals. Laser pulsations are shown to emerge organized in several hitherto unseen regular and irregular phases and to exhibit a much richer and complex range of behaviors than described thus far. A significant observation is that qualitatively similar organization of laser spiking and bursting can be obtained by tuning rather distinct control parameters, suggesting the existence of unexpected symmetries in the laser control space. PMID:26428560

  17. Self-organization of pulsing and bursting in a CO{sub 2} laser with opto-electronic feedback

    SciTech Connect

    Freire, Joana G.; Meucci, Riccardo; Arecchi, Fortunato Tito; and others

    2015-09-15

    We report a detailed investigation of the stability of a CO{sub 2} laser with feedback as described by a six-dimensional rate-equations model which provides satisfactory agreement between numerical and experimental results. We focus on experimentally accessible parameters, like bias voltage, feedback gain, and the bandwidth of the feedback loop. The impact of decay rates and parameters controlling cavity losses are also investigated as well as control planes which imply changes of the laser physical medium. For several parameter combinations, we report stability diagrams detailing how laser spiking and bursting is organized over extended intervals. Laser pulsations are shown to emerge organized in several hitherto unseen regular and irregular phases and to exhibit a much richer and complex range of behaviors than described thus far. A significant observation is that qualitatively similar organization of laser spiking and bursting can be obtained by tuning rather distinct control parameters, suggesting the existence of unexpected symmetries in the laser control space.

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

    PubMed

    Zrenner, Christoph; Belardinelli, Paolo; Müller-Dahlhaus, Florian; Ziemann, Ulf

    2016-01-01

    Closed-loop neuroscience is receiving increasing attention with recent technological advances that enable complex feedback loops to be implemented with millisecond resolution on commodity hardware. We summarize emerging conceptual and methodological frameworks that are available to experimenters investigating a "brain in the loop" using non-invasive brain stimulation and briefly review the experimental and therapeutic implications. We take the view that closed-loop neuroscience in fact deals with two conceptually quite different loops: a "brain-state dynamics" loop, used to couple with and modulate the trajectory of neuronal activity patterns, and a "task dynamics" loop, that is the bidirectional motor-sensory interaction between brain and (simulated) environment, and which enables goal-directed behavioral tasks to be incorporated. Both loops need to be considered and combined to realize the full experimental and therapeutic potential of closed-loop neuroscience. PMID:27092055

  19. Feedback Regulation and Its Efficiency in Biochemical Networks

    NASA Astrophysics Data System (ADS)

    Kobayashi, Tetsuya J.; Yokota, Ryo; Aihara, Kazuyuki

    2016-03-01

    Intracellular biochemical networks fluctuate dynamically due to various internal and external sources of fluctuation. Dissecting the fluctuation into biologically relevant components is important for understanding how a cell controls and harnesses noise and how information is transferred over apparently noisy intracellular networks. While substantial theoretical and experimental advancement on the decomposition of fluctuation was achieved for feedforward networks without any loop, we still lack a theoretical basis that can consistently extend such advancement to feedback networks. The main obstacle that hampers is the circulative propagation of fluctuation by feedback loops. In order to define the relevant quantity for the impact of feedback loops for fluctuation, disentanglement of the causally interlocked influences between the components is required. In addition, we also lack an approach that enables us to infer non-perturbatively the influence of the feedback to fluctuation in the same way as the dual reporter system does in the feedforward networks. In this work, we address these problems by extending the work on the fluctuation decomposition and the dual reporter system. For a single-loop feedback network with two components, we define feedback loop gain as the feedback efficiency that is consistent with the fluctuation decomposition for feedforward networks. Then, we clarify the relation of the feedback efficiency with the fluctuation propagation in an open-looped FF network. Finally, by extending the dual reporter system, we propose a conjugate feedback and feedforward system for estimating the feedback efficiency non-perturbatively only from the statistics of the system.

  20. Balanced-Bridge Feedback Control Of Motor

    NASA Technical Reports Server (NTRS)

    Lurie, Boris J.

    1990-01-01

    Sensitivity to variations in electrical and mechanical characteristics reduced. Proposed control system for motor-driven rotary actuator includes three nested feedback loops which, when properly designed, decoupled from each other. Intended to increase accuracy of control by mitigating such degrading effects as vibrations and variations in electrical and mechanical characteristics of structure rotated. Lends itself to optimization of performance via independent optimization of each of three loops. Includes outer, actuator, and driver feedback loops, configured so that actuator is subsystem, and driver is subsystem of actuator.

  1. Continuous control of phase-locked-loop bandwidth

    NASA Technical Reports Server (NTRS)

    Motal, G. W.; Vanelli, J. C.

    1980-01-01

    Tracking loop filter with continuous bandwidth control smooths transition from wide to narrow band. Circuit was designed for Space Shuttle where bandwidth varied between 320 Hz for acquisition and 20 Hz for tracking. Field-effect transitor (FET) acts as voltage controlled variable resistance, changing time constant of filter between phase detector and voltage-controlled oscillator in phase-locked loop.

  2. Electrometer preamplifier has drift correction feedback

    NASA Technical Reports Server (NTRS)

    Labarthe, L. C.

    1965-01-01

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

  3. Feedback Configuration Tools for LHC Low Level RF

    SciTech Connect

    Van Winkle, D.; Fox, J.; Mastorides, T.; Rivetta, C.; Baudrenghien, P.; Butterworth, A.; Molendijk, J.; /CERN

    2009-12-16

    The LHC Low Level RF System (LLRF) is a complex multi-VME crate system which is used to regulate the superconductive cavity gap voltage as well as to lower the impedance as seen by the beam through low latency feedback. This system contains multiple loops with several parameters to be set before the loops can be closed. In this paper, we present a suite of MATLAB based tools developed to perform the preliminary alignment of the RF stations and the beginnings of a closed loop model based alignment routine. We briefly introduce the RF system and in particular the base band (time domain noise based) network analyzer system built into the LHC LLRF. The main focus of this paper is the methodology of the algorithms used by the routines within the context of the overall system. Measured results are presented that validate the technique. Because the RF systems are located in a cavern 120 m underground in a location which is relatively un-accessible without beam and completely un-accessible with beam present or magnets are energized, these remotely operated tools are a necessity for the CERN LLRF team to maintain and tune their LLRF systems in a similar fashion as to what was done very successfully in PEP-II at SLAC.

  4. A Novel Digital Closed Loop MEMS Accelerometer Utilizing a Charge Pump.

    PubMed

    Chu, Yixing; Dong, Jingxin; Chi, Baoyong; Liu, Yunfeng

    2016-01-01

    This paper presents a novel digital closed loop microelectromechanical system (MEMS) accelerometer with the architecture and experimental evaluation. The complicated timing diagram or complex power supply in published articles are circumvented by using a charge pump system of adjustable output voltage fabricated in a 2P4M 0.35 µm complementary metal-oxide semiconductor (CMOS) process, therefore making it possible for interface circuits of MEMS accelerometers to be integrated on a single die on a large scale. The output bitstream of the sigma delta modulator is boosted by the charge pump system and then applied on the feedback comb fingers to form electrostatic forces so that the MEMS accelerometer can operate in a closed loop state. Test results agree with the theoretical formula nicely. The nonlinearity of the accelerometer within ±1 g is 0.222% and the long-term stability is about 774 µg. PMID:26999157

  5. A Novel Digital Closed Loop MEMS Accelerometer Utilizing a Charge Pump

    PubMed Central

    Chu, Yixing; Dong, Jingxin; Chi, Baoyong; Liu, Yunfeng

    2016-01-01

    This paper presents a novel digital closed loop microelectromechanical system (MEMS) accelerometer with the architecture and experimental evaluation. The complicated timing diagram or complex power supply in published articles are circumvented by using a charge pump system of adjustable output voltage fabricated in a 2P4M 0.35 µm complementary metal-oxide semiconductor (CMOS) process, therefore making it possible for interface circuits of MEMS accelerometers to be integrated on a single die on a large scale. The output bitstream of the sigma delta modulator is boosted by the charge pump system and then applied on the feedback comb fingers to form electrostatic forces so that the MEMS accelerometer can operate in a closed loop state. Test results agree with the theoretical formula nicely. The nonlinearity of the accelerometer within ±1 g is 0.222% and the long-term stability is about 774 µg. PMID:26999157

  6. Feedback analysis and design of RF power links for low-power bionic systems.

    PubMed

    Baker, M W; Sarpeshkar, R

    2007-03-01

    This paper presents a feedback-loop technique for analyzing and designing RF power links for transcutaneous bionic systems, i.e., between an external RF coil and an internal RF coil implanted inside the body. The feedback techniques shed geometric insight into link design and minimize algebraic manipulations. We demonstrate that when the loop transmission of the link's feedback loop is -1, the link is critically coupled, i.e., the magnitude of the voltage transfer function across the link is maximal. We also derive an optimal loading condition that maximizes the energy efficiency of the link and use it as a basis for our link design. We present an example of a bionic implant system designed for load power consumptions in the 1-10-mW range, a low-power regime not significantly explored in prior designs. Such low power levels add to the challenge of link efficiency, because the overhead associated with switching losses in power amplifiers at the link input and with rectifiers at the link output significantly degrade link efficiency. We describe a novel integrated Class-E power amplifier design that uses a simple control strategy to minimize such losses. At 10-mW load power consumption, we measure overall link efficiencies of 74% and 54% at 1- and 10-mm coil separations, respectively, in good agreement with our theoretical predictions of the link's efficiency. At 1-mW load power consumption, we measure link efficiencies of 67% and 51% at 1- and 10-mm coil separations, respectively, also in good accord with our theoretical predictions. In both cases, the link's rectified output dc voltage varied by less than 16% over link distances that ranged from 2 to 10 mm. PMID:23851518

  7. 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.

  8. A Current-Mode Common-Mode Feedback Circuit (CMFB) with Rail-to-Rail Operation

    NASA Astrophysics Data System (ADS)

    Suadet, Apirak; Kasemsuwan, Varakorn

    2011-03-01

    This paper presents a current-mode common-mode feedback (CMFB) circuit with rail-to-rail operation. The CMFB is a stand-alone circuit, which can be connected to any low voltage transconductor without changing or upsetting the existing circuit. The proposed CMFB employs current mirrors, operating as common-mode detector and current amplifier to enhance the loop gain of the CMFB. The circuit employs positive feedback to enhance the output impedance and gain. The circuit has been designed using a 0.18 μm CMOS technology under 1V supply and analyzed using HSPICE with BSIM3V3 device models. A pseudo-differential amplifier using two common sources and the proposed CMFB shows rail to rail output swing (± 0.7 V) with low common-mode gain (-36 dB) and power dissipation of 390 μW.

  9. Multiloop Rapid-Rise/Rapid Fall High-Voltage Power Supply

    NASA Technical Reports Server (NTRS)

    Bearden, Douglas

    2007-01-01

    A proposed multiloop power supply would generate a potential as high as 1.25 kV with rise and fall times <100 s. This power supply would, moreover, be programmable to generate output potentials from 20 to 1,250 V and would be capable of supplying a current of at least 300 A at 1,250 V. This power supply is intended to be a means of electronic shuttering of a microchannel plate that would be used to intensify the output of a charge-coupled-device imager to obtain exposure times as short as 1 ms. The basic design of this power supply could also be adapted to other applications in which high voltages and high slew rates are needed. At the time of reporting the information for this article, there was no commercially available power supply capable of satisfying the stated combination of voltage, rise-time, and fall-time requirements. The power supply would include a preregulator that would be used to program a voltage 1/30 of the desired output voltage. By means of a circuit that would include a pulse-width modulator (PWM), two voltage doublers, and a transformer having two primary and two secondary windings, the preregulator output voltage would be amplified by a factor of 30. A resistor would limit the current by controlling a drive voltage applied to field-effect transistors (FETs) during turn-on of the PWM. Two feedback loops would be used to regulate the high output voltage. A pulse transformer would be used to turn on four FETs to short-circuit output capacitors when the outputs of the PWM were disabled. Application of a 0-to-5-V square to a PWM shut-down pin would cause a 20-to-1,250-V square wave to appear at the output.

  10. 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

  11. Closed-Loop, Multichannel Experimentation Using the Open-Source NeuroRighter Electrophysiology Platform

    PubMed Central

    Newman, Jonathan P.; Zeller-Townson, Riley; Fong, Ming-Fai; Arcot Desai, Sharanya; Gross, Robert E.; Potter, Steve M.

    2013-01-01

    Single neuron feedback control techniques, such as voltage clamp and dynamic clamp, have enabled numerous advances in our understanding of ion channels, electrochemical signaling, and neural dynamics. Although commercially available multichannel recording and stimulation systems are commonly used for studying neural processing at the network level, they provide little native support for real-time feedback. We developed the open-source NeuroRighter multichannel electrophysiology hardware and software platform for closed-loop multichannel control with a focus on accessibility and low cost. NeuroRighter allows 64 channels of stimulation and recording for around US $10,000, along with the ability to integrate with other software and hardware. Here, we present substantial enhancements to the NeuroRighter platform, including a redesigned desktop application, a new stimulation subsystem allowing arbitrary stimulation patterns, low-latency data servers for accessing data streams, and a new application programming interface (API) for creating closed-loop protocols that can be inserted into NeuroRighter as plugin programs. This greatly simplifies the design of sophisticated real-time experiments without sacrificing the power and speed of a compiled programming language. Here we present a detailed description of NeuroRighter as a stand-alone application, its plugin API, and an extensive set of case studies that highlight the system’s abilities for conducting closed-loop, multichannel interfacing experiments. PMID:23346047

  12. A multiple-pass ring oscillator based dual-loop phase-locked loop

    NASA Astrophysics Data System (ADS)

    Danfeng, Chen; Junyan, Ren; Jingjing, Deng; Wei, Li; Ning, Li

    2009-10-01

    A dual-loop phase-locked loop (PLL) for wideband operation is proposed. The dual-loop architecture combines a coarse-tuning loop with a fine-tuning one, enabling a wide tuning range and low voltage-controlled oscillator (VCO) gain without poisoning phase noise and reference spur suppression performance. An analysis of the phase noise and reference spur of the dual-loop PLL is emphasized. A novel multiple-pass ring VCO is designed for the dual-loop application. It utilizes both voltage-control and current-control simultaneously in the delay cell. The PLL is fabricated in Jazz 0.18-μm RF CMOS technology. The measured tuning range is from 4.2 to 5.9 GHz. It achieves a low phase noise of -99 dBc/Hz @ 1 MHz offset from a 5.5 GHz carrier.

  13. 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.

  14. 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.

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

    PubMed

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

    2016-05-01

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

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

    NASA Technical Reports Server (NTRS)

    Quirk, K. J.; Srinivasan, M.

    2002-01-01

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

  17. Coress feedback

    PubMed Central

    2012-01-01

    This issue of CORESS feedback highlights yet again the importance of checking medications before administration and of adequate handover. Documentation of important medical data including drug allergies, as failed to happen in the case described below, is vital. We are grateful to the clinicians who have provided the material for these reports. The online reporting form is on our website (www.coress.org.uk), which also includes all previous feedback reports. Published contributions will be acknowledged by a ‘Certificate of Contribution’, which may be included in the contributor’s record of continuing professional development.

  18. Single SQUID multiplexer for arrays of voltage-biased superconducting bolometers

    SciTech Connect

    Yoon, Jongsoo; Clarke, John; Gildemeister, J.M.; Lee, Adrian T.; Myers, M.J.; Richards, P.L.; Skidmore, J.T.; Spieler, H.G.

    2001-08-20

    We describe a frequency domain superconducting quantum interference device (SQUID) multiplexer which monitors a row of low-temperature sensors simultaneously with a single SQUID. Each sensor is ac biased with a unique frequency and all the sensor currents are added in a superconducting summing loop. A single SQUID measures the current in the summing loop, and the individual signals are lock-in detected after the room temperature SQUID electronics. The current in the summing loop is nulled by feedback to eliminate direct crosstalk. In order to avoid the accumulation of Johnson noise in the summing loop, a tuned bandpass filter is inserted in series with each sensor. For a 32-channel multiplexer for Voltage-biased Superconducting Bolometer (VSB) with a time constant {approx}1msec, we estimate that bias frequencies in the range from {approx}500kHz to {approx}600kHz are practical. The major limitation of our multiplexing scheme is in the slew rate of a readout SQUID. We discuss a ''carrier nulling'' technique which could be used to increase the number of sensors in a row or to multiplex faster bolometers by reducing the required slew rate for a readout SQUID.

  19. Low distortion automatic phase control circuit. [voltage controlled phase shifter

    NASA Technical Reports Server (NTRS)

    Hauge, G.; Pederson, C. W. (Inventor)

    1974-01-01

    A voltage controlled phase shifter is rendered substantially harmonic distortion free over a large dynamic input range by employing two oppositely poled, equally biased varactor diodes as the voltage controlled elements which adjust the phase shift. Control voltages which affect the bias of both diodes equally are used to adjust the phase shift without increasing distortion. A feedback stabilized phase shifter is rendered substantially frequency independent by employing a phase detector to control the phase shift of the voltage controlled phase shifter.

  20. Low power, scalable multichannel high voltage controller

    DOEpatents

    Stamps, James Frederick; Crocker, Robert Ward; Yee, Daniel Dadwa; Dils, David Wright

    2006-03-14

    A low voltage control circuit is provided for individually controlling high voltage power provided over bus lines to a multitude of interconnected loads. An example of a load is a drive for capillary channels in a microfluidic system. Control is distributed from a central high voltage circuit, rather than using a number of large expensive central high voltage circuits to enable reducing circuit size and cost. Voltage is distributed to each individual load and controlled using a number of high voltage controller channel switches connected to high voltage bus lines. The channel switches each include complementary pull up and pull down photo isolator relays with photo isolator switching controlled from the central high voltage circuit to provide a desired bus line voltage. Switching of the photo isolator relays is further controlled in each channel switch using feedback from a resistor divider circuit to maintain the bus voltage swing within desired limits. Current sensing is provided using a switched resistive load in each channel switch, with switching of the resistive loads controlled from the central high voltage circuit.

  1. Low power, scalable multichannel high voltage controller

    DOEpatents

    Stamps, James Frederick; Crocker, Robert Ward; Yee, Daniel Dadwa; Dils, David Wright

    2008-03-25

    A low voltage control circuit is provided for individually controlling high voltage power provided over bus lines to a multitude of interconnected loads. An example of a load is a drive for capillary channels in a microfluidic system. Control is distributed from a central high voltage circuit, rather than using a number of large expensive central high voltage circuits to enable reducing circuit size and cost. Voltage is distributed to each individual load and controlled using a number of high voltage controller channel switches connected to high voltage bus lines. The channel switches each include complementary pull up and pull down photo isolator relays with photo isolator switching controlled from the central high voltage circuit to provide a desired bus line voltage. Switching of the photo isolator relays is further controlled in each channel switch using feedback from a resistor divider circuit to maintain the bus voltage swing within desired limits. Current sensing is provided using a switched resistive load in each channel switch, with switching of the resistive loads controlled from the central high voltage circuit.

  2. Constant voltage electro-slag remelting control

    DOEpatents

    Schlienger, Max E.

    1996-01-01

    A system for controlling electrode gap in an electro-slag remelt furnace has a constant regulated voltage and an eletrode which is fed into the slag pool at a constant rate. The impedance of the circuit through the slag pool is directly proportional to the gap distance. Because of the constant voltage, the system current changes are inversely proportional to changes in gap. This negative feedback causes the gap to remain stable.

  3. Constant voltage electro-slag remelting control

    DOEpatents

    Schlienger, M.E.

    1996-10-22

    A system for controlling electrode gap in an electro-slag remelt furnace has a constant regulated voltage and an electrode which is fed into the slag pool at a constant rate. The impedance of the circuit through the slag pool is directly proportional to the gap distance. Because of the constant voltage, the system current changes are inversely proportional to changes in gap. This negative feedback causes the gap to remain stable. 1 fig.

  4. 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.

  5. Feedback Amplification of Neutrophil Function.

    PubMed

    Németh, Tamás; Mócsai, Attila

    2016-06-01

    As the first line of innate immune defense, neutrophils need to mount a rapid and robust antimicrobial response. Recent studies implicate various positive feedback amplification processes in achieving that goal. Feedback amplification ensures effective migration of neutrophils in shallow chemotactic gradients, multiple waves of neutrophil recruitment to the site of inflammation, and the augmentation of various effector functions of the cells. We review here such positive feedback loops including intracellular and autocrine processes, paracrine effects mediated by lipid (LTB4), chemokine, and cytokine mediators, and bidirectional interactions with the complement system and with other immune and non-immune cells. These amplification mechanisms are not only involved in antimicrobial immunity but also contribute to neutrophil-mediated tissue damage under pathological conditions. PMID:27157638

  6. 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.

  7. 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.

  8. Closed-loop pulsed helium ionization detector

    DOEpatents

    Ramsey, Roswitha S.; Todd, Richard A.

    1987-01-01

    A helium ionization detector for gas chromatography is operated in a constant current, pulse-modulated mode by configuring the detector, electrometer and a high voltage pulser in a closed-loop control system. The detector current is maintained at a fixed level by varying the frequency of fixed-width, high-voltage bias pulses applied to the detector. An output signal proportional to the pulse frequency is produced which is indicative of the charge collected for a detected species.

  9. A battery-based, low-noise voltage source

    NASA Astrophysics Data System (ADS)

    Wagner, Anke; Sturm, Sven; Schabinger, Birgit; Blaum, Klaus; Quint, Wolfgang

    2010-06-01

    A highly stable, low-noise voltage source was designed to improve the stability of the electrode bias voltages of a Penning trap. To avoid excess noise and ground loops, the voltage source is completely independent of the public electric network and uses a 12 V car battery to generate output voltages of ±15 and ±5 V. First, the dc supply voltage is converted into ac-voltage and gets amplified. Afterwards, the signal is rectified, filtered, and regulated to the desired output value. Each channel can deliver up to 1.5 A. The current as well as the battery voltage and the output voltages can be read out via a universal serial bus (USB) connection for monitoring purposes. With the presented design, a relative voltage stability of 7×10-7 over 6.5 h and a noise level equal or smaller than 30 nV/√Hz is achieved.

  10. A battery-based, low-noise voltage source.

    PubMed

    Wagner, Anke; Sturm, Sven; Schabinger, Birgit; Blaum, Klaus; Quint, Wolfgang

    2010-06-01

    A highly stable, low-noise voltage source was designed to improve the stability of the electrode bias voltages of a Penning trap. To avoid excess noise and ground loops, the voltage source is completely independent of the public electric network and uses a 12 V car battery to generate output voltages of +/-15 and +/-5 V. First, the dc supply voltage is converted into ac-voltage and gets amplified. Afterwards, the signal is rectified, filtered, and regulated to the desired output value. Each channel can deliver up to 1.5 A. The current as well as the battery voltage and the output voltages can be read out via a universal serial bus (USB) connection for monitoring purposes. With the presented design, a relative voltage stability of 7 x 10(-7) over 6.5 h and a noise level equal or smaller than 30 nV/square root(Hz) is achieved. PMID:20590260

  11. Feedback linearization application for LLRF control system

    SciTech Connect

    Kwon, S.; Regan, A.; Wang, Y.M.; Rohlev, T.

    1999-06-01

    The Low Energy Demonstration Accelerator (LEDA) being constructed at Los Alamos National Laboratory will serve as the prototype for the low energy section of Acceleration Production of Tritium (APT) accelerator. This paper addresses the problem of the LLRF control system for LEDA. The authors propose a control law which is based on exact feedback linearization coupled with gain scheduling which reduces the effect of the deterministic klystron cathode voltage ripple that is due to harmonics of the high voltage power supply and achieves tracking of desired set points. Also, they propose an estimator of the ripple and its time derivative and the estimates based feedback linearization controller.

  12. Feedback linearization application for LLRF control system

    SciTech Connect

    Kwon, S.; Regan, A.; Wang, Y.M.; Rohlev, T.

    1998-12-31

    The Low Energy Demonstration Accelerator (LEDA) being constructed at Los Alamos National Laboratory will serve as the prototype for the low energy section of Acceleration Production of Tritium (APT) accelerator. This paper addresses the problem of the LLRF control system for LEDA. The authors propose a control law which is based on exact feedback linearization coupled with gain scheduling which reduces the effect of the deterministic klystron cathode voltage ripple that is due to harmonics of the high voltage power supply and achieves tracking of desired set points. Also, they propose an estimator of the ripple and its time derivative and the estimates based feedback linearization controller.

  13. 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.

  14. CORESS feedback

    PubMed Central

    2012-01-01

    This edition of CORESS feedback reinforces the very basic principles of obtaining and using an accurate history and examination to make an appropriate diagnosis in the face of equivocal or uninformative investigations and failing equipment. Case 126 illustrates once again the potential deleterious consequences of failing to check a drug correctly prior to administration. We are grateful to the clinicians who have provided the material for these reports. The online reporting form is on our website (www.coress.org.uk), which also includes all previous feedback reports. Published contributions will be acknowledged by a ‘Certificate of Contribution’, which may be included in the contributor’s record of continuing professional development. CORESS relies heavily on the expertise of the specialty members of the Advisory Board in the preparation of feedback reports and dissemination of safety information related to surgical practice. The organisation is grateful to the following members of the Advisory Board and Board of Directors who have contributed to published reports in 2010 and 2011: Board of Directors: Viscount Bridgeman, Mr Chris Chilton, Mr Martin Else, Professor Nicholas Gair, Mr Adam Lewis CVO, Miss Clare Marx, Mr Andrew May, Lord Bernard Ribeiro, Mr Frank Smith, Mr Peter Tait, Mr Denis Wilkins. Advisory Board: Ms E Baird, Mr Daryl I Baker, Mr Ken Catchpole, Dr Lauren Morgan, Mr Stephen Clark, Mr Robert Davies, Mr Mark Deakin, Ms D Eastwood, Mr Barry Ferris, Mr Mark Fordham, Mr Paul J Gibbs, Mr Grey Giddins, Mr Robert Greatorex, Mr Mervyn Griffiths, Mr John Hammond, Mr William Harkness, Mr M Hemadri, Mr Richard Holdsworth, Miss Claire Hopkins, Professor Zygmunt Krukowski, Mr N Mamode, Mr Ian Martin, Surgeon Commander Mark Midwinter, Mr J Richard Novell, Professor Gerald O’Sullivan, Dr Gerard Panting, Mr Mike Pittam, Dr Mike Powers QC, Ms Patricia Scott, Professor Alastair Thompson, Dr J P van Besouw, Mr Mark Vipond, Mr David Webster, Mr Michael Wyatt.

  15. Damping improvement and terminal voltage regulation for a synchronous machine using an energy storage device

    NASA Astrophysics Data System (ADS)

    Kim, Seok-Kyoon; Song, Hwachang; Yoon, Tae-Woong

    2015-04-01

    On the basis of the non-linear third-order generator model, this article proposes a dual control scheme for a single synchronous machine equipped with an energy storage device to regulate the terminal voltage while enhancing the damping. Based on the input-output feedback linearisation method, the exciter controller is designed such that the terminal voltage robustly converges to its predetermined reference in the presence of a model uncertainty. In addition, the control input of the energy storage device feedbacks only the relative speed. It is shown that this controller can effectively increase the damping of the synchronous machine and that there is a set of initial conditions such that all trajectories started from this set go to the equilibrium point, satisfying input constraints. Moreover, it is also verified that all generator variables are bounded except for the power angle. The simulation results show that the closed-loop performance is satisfactory despite a transmission line fault and a model uncertainty in which the non-linear fourth-order generator model (two-axis) is used.

  16. A dual-loop model of the human controller

    NASA Technical Reports Server (NTRS)

    Hess, R. A.

    1977-01-01

    A representative model of the human controller in single-axis compensatory tracking tasks that exhibits an internal feedback loop which is not evident in single-loop models now in common use is presented. This hypothetical inner-loop involves a neuromuscular command signal derived from the time rate of change of controlled element output which is due to control activity. It is not contended that the single-loop human controller models now in use are incorrect, but that they contain an implicit but important internal loop closure, which, if explicitly considered, can account for a good deal of the adaptive nature of the human controller in a systematic manner.

  17. Feedbacks and landscape-level vegetation dynamics.

    PubMed

    Bowman, David M J S; Perry, George L W; Marston, J B

    2015-05-01

    Alternative stable-state theory (ASS) is widely accepted as explaining landscape-level vegetation dynamics, such as switches between forest and grassland. This theory argues that webs of feedbacks stabilise vegetation composition and structure, and that abrupt state shifts can occur if stabilising feedbacks are weakened. However, it is difficult to identify stabilising feedback loops and the disturbance thresholds beyond which state changes occur. Here, we argue that doing this requires a synthetic approach blending observation, experimentation, simulation, conceptual models, and narratives. Using forest boundaries and large mammal extinctions, we illustrate how a multifaceted research program can advance understanding of feedback-driven ecosystem change. Our integrative approach has applicability to other complex macroecological systems controlled by numerous feedbacks where controlled experimentation is impossible. PMID:25837918

  18. Feasibility Study of a 6.6kV, 1MW Transformerless BTB-Based Loop Controller

    NASA Astrophysics Data System (ADS)

    Yonetani, Shinsuke; Fujita, Hideaki; Akagi, Hirofumi; Okada, Naotaka

    This paper achieves a feasibility study of a 6.6kV, 1MW loop controller that consists of a transformerless back-to-back configuration using two 5-level diode-clamped converters. However, the loop controller requires reducing the zero-sequence current circulating between the two distribution lines below than 0.2 A in rms, in order to avoid malfunction of line-to-ground fault protection relays. Moreover, all the dc voltages across four capacitors in the dc link have to be controlled equally. This paper presents a solution to these problems. Two common-mode chokes are installed at the ac side of each converter to suppress high-frequency zero-sequence currents, while feedback control is applied to eliminate low-frequency zero-sequence currents. Two bidirectional buck-boost dc-dc converters are employed to keep the four capacitor voltages equal. Simulation results verify viability and effectiveness of the loop controller, along with the developed theoretical analysis.

  19. 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.

  20. Rollercoaster Loop Shapes

    ERIC Educational Resources Information Center

    Pendrill, Ann-Marie

    2005-01-01

    Many modern rollercoasters feature loops. Although textbook loops are often circular, real rollercoaster loops are not. In this paper, we look into the mathematical description of various possible loop shapes, as well as their riding properties. We also discuss how a study of loop shapes can be used in physics education.

  1. Rollercoaster loop shapes

    NASA Astrophysics Data System (ADS)

    Pendrill, Ann-Marie

    2005-11-01

    Many modern rollercoasters feature loops. Although textbook loops are often circular, real rollercoaster loops are not. In this paper, we look into the mathematical description of various possible loop shapes, as well as their riding properties. We also discuss how a study of loop shapes can be used in physics education.

  2. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  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. 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.

  6. 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)

  7. Time-Delayed Quantum Feedback Control

    NASA Astrophysics Data System (ADS)

    Grimsmo, Arne L.

    2015-08-01

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

  8. Time-Delayed Quantum Feedback Control.

    PubMed

    Grimsmo, Arne L

    2015-08-01

    A theory of time-delayed coherent quantum feedback is developed. More specifically, we consider a quantum system coupled to a bosonic reservoir creating a unidirectional feedback loop. It is shown that the dynamics can be mapped onto a fictitious series of cascaded quantum systems, where the system is driven by past versions of itself. The derivation of this model relies on a tensor network representation of the system-reservoir time propagator. For concreteness, this general theory is applied to a driven two-level atom scattering into a coherent feedback loop. We demonstrate how delay effects can qualitatively change the dynamics of the atom and how quantum control can be implemented in the presence of time delays. PMID:26296104

  9. Low voltage surface transverse wave oscillators for the next generation CMOS technology.

    PubMed

    Avramov, Ivan D

    2005-08-01

    The design and performance of voltage controlled surface transverse wave oscillators (VCSTWO) in the lower gigahertz frequency range, operating on supply and tuning voltages in the 1.2 to 3.3 V range, and suitable for direct interfacing with the next generation CMOS circuits are presented. By applying the "boost" principle, as used in direct current (DC)-DC converters, to the design of the sustaining amplifier, the VCSTWO outputs are switched between 0 V and a positive peak value, exceeding the supply voltage Us, to provide safe CMOS-circuit switching while keeping the radio frequency (RF)/DC efficiency to a maximum for low DC power consumption. The investigated 1.0 and 2.5 GHz VCSTWO are varactor tuned feedback-loop oscillators stabilized with two-port surface transverse wave (STW) resonators. Each VCSTWO has a DC-coupled, high-impedance switched output to drive the CMOS circuit directly, and an additional sinusoidal 50 ohmz high-power reference output available for other low-noise system applications. Phase noise levels in the -103 to -115 dBc/Hz range at 1 kHz carrier offset are achieved with 1.0 GHz VCSTWO at a RF/DC efficiency in the 21 to 29% range. The 2.5 GHz prototypes demonstrate phase noise levels in the -97 to -102 dBc/Hz range at 1 kHz carrier offset, and efficiencies range between 8 and 15%. PMID:16245594

  10. 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

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

    NASA Technical Reports Server (NTRS)

    Castell, Karen D. (Inventor); Ruitberg, Arthur P. (Inventor)

    1994-01-01

    A high voltage power supply in a dc-dc converter configuration includes a pre-regulator which filters and regulates the dc input and drives an oscillator which applies, in turn, a low voltage ac signal to the low side of a step-up high voltage transformer. The high voltage side of the transformer drives a voltage multiplier which provides a stepped up dc voltage to an output filter. The output voltage is sensed by a feedback network which then controls a regulator. Both the input and output of the regulator are on the high voltage side, avoiding isolation problems. The regulator furnishes a portion of the drive to the voltage multiplier, avoiding having a regulator in series with the load with its attendant, relatively high power losses. This power supply is highly regulated, has low power consumption, a low parts count and may be manufactured at low cost. The power supply has a programmability feature that allows for the selection of a large range of output voltages.

  12. Magnetic-Flux-Compensated Voltage Divider

    NASA Technical Reports Server (NTRS)

    Mata, Carlos T.

    2005-01-01

    A magnetic-flux-compensated voltage-divider circuit has been proposed for use in measuring the true potential across a component that is exposed to large, rapidly varying electric currents like those produced by lightning strikes. An example of such a component is a lightning arrester, which is typically exposed to currents of the order of tens of kiloamperes, having rise times of the order of hundreds of nanoseconds. Traditional voltage-divider circuits are not designed for magnetic-flux-compensation: They contain uncompensated loops having areas large enough that the transient magnetic fluxes associated with large transient currents induce spurious voltages large enough to distort voltage-divider outputs significantly. A drawing of the proposed circuit was not available at the time of receipt of information for this article. What is known from a summary textual description is that the proposed circuit would contain a total of four voltage dividers: There would be two mixed dividers in parallel with each other and with the component of interest (e.g., a lightning arrester), plus two mixed dividers in parallel with each other and in series with the component of interest in the same plane. The electrical and geometric configuration would provide compensation for induced voltages, including those attributable to asymmetry in the volumetric density of the lightning or other transient current, canceling out the spurious voltages and measuring the true voltage across the component.

  13. 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.

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

    PubMed

    Çilingiroğlu, Uğur; İpek, Sercan

    2013-08-01

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

  15. Feedback stitching for gigapixel video

    NASA Astrophysics Data System (ADS)

    Marks, Daniel L.; Bange, Lauren M.; Brady, David J.

    2015-11-01

    Methods of stitching static panoramas are unsuitable for video-rate stitching from camera arrays, because these methods are too computationally intensive for real-time operation and do not take advantage of prior knowledge of camera positions or the coherence between successive frames of a video sequence. We propose feedback stitching, which embeds the stitching process in a feedback loop, so that as new frames are captured, any new stitching errors occurring in the video sequence are analyzed and corrected as the sequence progresses. These algorithms are suitable for multiscale cameras, a camera array technology proven to be capable of gigapixel snapshot and video imaging, to allow for real-time compensation of any registration or parallax errors.

  16. Stability analysis and compensation of a boost regulator with two-loop control

    NASA Technical Reports Server (NTRS)

    Wester, G. W.

    1974-01-01

    A useful stability measure has been demonstrated by Wester (1973) for switching regulators with a single feedback loop by applying the Nyquist criterion to the approximate loop gain determined by a time-averaging technique. This approach is extended and applied to the characterization, stability analysis, and compensation design of a switching regulator with two-loop control. The role and relative significance of each control loop is clarified on the basis of a description of circuit operation, and the major and minor loops are identified. In view of the inapplicability of linear feedback theory, describing functions of the feedback loops and power stage are derived, using small-signal analysis. Several phenomena revealed from an analysis of the major loop gain are discussed.

  17. Semiclassical spin-spin dynamics and feedback control in transport through a quantum dot

    NASA Astrophysics Data System (ADS)

    Mosshammer, Klemens; Brandes, Tobias

    2014-10-01

    We present a theory of magnetotransport through an electronic orbital, where the electron spin interacts with a (sufficiently) large external spin via an exchange interaction. Using a semiclassical approximation, we derive a set of equations of motions for the electron density matrix and the mean value of the external spin that turns out to be highly nonlinear. The dissipation via the electronic leads is implemented in terms of a quantum master equation that is combined with the nonlinear terms of the spin-spin interaction. With an anisotropic exchange coupling a variety of dynamics is generated, such as self-sustained oscillations with parametric resonances or even chaotic behavior. Within our theory we can integrate a Maxwell-demon-like closed-loop feedback scheme that is capable of transporting particles against an applied bias voltage and that can be used to implement a spin filter to generate spin-dependent oscillating currents of opposite directions.

  18. Continuous flow total artificial heart: modeling and feedback control in a mock circulatory system.

    PubMed

    Khalil, Hassan A; Kerr, Daniel T; Franchek, Matthew A; Metcalfe, Ralph W; Benkowski, Robert J; Cohn, William E; Tuzun, Egemen; Radovancevic, Branislav; Frazier, O H; Kadipasaoglu, Kamuran A

    2008-01-01

    We developed a mock circulatory loop and used mathematical modeling to test the in vitro performance of a physiologic flow control system for a total artificial heart (TAH). The TAH was constructed from two continuous flow pumps. The objective of the control system was to maintain loop flow constant in response to changes in outflow resistance of either pump. Baseline outflow resistances of the right (pulmonary vascular resistance) and the left (systemic vascular resistance) pumps were set at 2 and 18 Wood units, respectively. The corresponding circuit flow was 4 L/min. The control system consisted of two digital integral controllers, each regulating the voltage, hence, the rotational speed of one of the pumps. The in vitro performance of the flow control system was validated by increasing systemic and pulmonary vascular resistances in the mock loop by 4 and 8 Wood units (simulating systemic and pulmonary hypertension conditions), respectively. For these simulated hypertensive states, the flow controllers regulated circuit flow back to 4 L/min within seconds by automatically adjusting the rotational speed of either or both pumps. We conclude that this multivariable feedback mechanism may constitute an adequate supplement to the inherent pressure sensitivity of rotary blood pumps for the automatic flow control and left-right flow balance of a dual continuous flow pump TAH system. PMID:18496274

  19. Building steady-state simulators via hierarchical feedback decomposition

    SciTech Connect

    Rouquette, N.

    1996-12-31

    In recent years, compositional modeling and self-explanatory simulation techniques have simplified the process of building dynamic simulators of physical systems. Building steady-state simulators is, conceptually, a simpler task consisting in solving a set algebraic equations. This simplicity hides delicate technical issues of convergence and search-space size due to the potentially large number of unknown parameters. We present an automated technique for reducing the dimensionality of the problem by (1) automatically identifying feedback loops (a generally NP-complete problem), (2) hierarchically decomposing the set of equations in terms of feedback loops, and (3) structuring a simulator where equations are solved either serially without search or in isolation within a feedback loop. This paper describes the key algorithms and the results of their implementation on building simulators for a two-phase evaporator loop system across multiple combinations of causal and non-causal approximations.

  20. Voltage Regulation of Connexin Channel Conductance

    PubMed Central

    Oh, Seunghoon

    2015-01-01

    Voltage is an important parameter that regulates the conductance of both intercellular and plasma membrane channels (undocked hemichannels) formed by the 21 members of the mammalian connexin gene family. Connexin channels display two forms of voltage-dependence, rectification of ionic currents and voltage-dependent gating. Ionic rectification results either from asymmetries in the distribution of fixed charges due to heterotypic pairing of different hemichannels, or by channel block, arising from differences in the concentrations of divalent cations on opposite sides of the junctional plaque. This rectification likely underpins the electrical rectification observed in some electrical synapses. Both intercellular and undocked hemichannels also display two distinct forms of voltage-dependent gating, termed Vj (fast)-gating and loop (slow)-gating. This review summarizes our current understanding of the molecular determinants and mechanisms underlying these conformational changes derived from experimental, molecular-genetic, structural, and computational approaches. PMID:25510741

  1. Feedbacks in Human-Landscape Systems

    NASA Astrophysics Data System (ADS)

    Chin, Anne; Florsheim, Joan L.; Wohl, Ellen; Collins, Brian D.

    2014-01-01

    This article identifies key questions and challenges for geomorphologists in investigating coupled feedbacks in human-landscape systems. While feedbacks occur in the absence of human influences, they are also altered by human activity. Feedbacks are a key element to understanding human-influenced geomorphic systems in ways that extend our traditional approach of considering humans as unidirectional drivers of change. Feedbacks have been increasingly identified in Earth-environmental systems, with studies of coupled human-natural systems emphasizing ecological phenomena in producing emerging concepts for social-ecological systems. Enormous gaps or uncertainties in knowledge remain with respect to understanding impact-feedback loops within geomorphic systems with significant human alterations, where the impacted geomorphic systems in turn affect humans. Geomorphology should play an important role in public policy by identifying the many diffuse and subtle feedbacks of both local- and global-scale processes. This role is urgent, while time may still be available to mitigate the impacts that limit the sustainability of human societies. Challenges for geomorphology include identification of the often weak feedbacks that occur over varied time and space scales ranging from geologic time to single isolated events and very short time periods, the lack of available data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, the varied tools and metrics needed to represent both physical and human processes, and the need to collaborate with social scientists with expertise in the human causes of geomorphic change, as well as the human responses to such change.

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

    PubMed Central

    Gong, Jian; Kim, Chang-Jin “CJ”

    2009-01-01

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

  3. Reduction of the apparent impedance of wide band accelerating cavities by RF feedback

    SciTech Connect

    Boussard, D.; Lambert, G.

    1983-08-01

    In the CERN SPS proton synchrotron the four accelerating cavities are of the travelling wave structure type. At the 10 GeV/c injection energy the cavities present to the beam an impedance very similar to that of a detuned RLC cavity with the result that strong dipole and quadrupole instabilities occur. The SPS accelerated beam current was limited by the combined action of these two effects to 2.5 X 10/sup 13/ protons which resulted in capture losses increasing with the injected beam intensity. Among the solutions possible for this problem, the RF feedback, which would alleviate both transient beam loading and instability effects, looked to the authors to be the most promising. In such a system the total voltage seen by the beam is reinjected into the feedback cavity via its power amplifier. Without any delay in the system the cavity impedance seen by the beam could be greatly reduced. Unfortunately the long delay in the system severely limits the bandwidth and the RF feedback could hardly correct more than the n = O beam loading component. The authors circumvented this problem by observing that they needed a large gain only in the vicinities of the RF frequencies. Outside these bands the phase rotation due to the long delay is unimportant if the gain is made low enough. If, in addition, the total delay of the system is made exactly equal to one machine turn, the open loop phase of the feedback system is always zero for each RF frequency. The two ingredients needed to make the RF feedback work for n not too small are therefore a transfer function with comb filter shape and a total delay of one machine turn. In this paper these ingredients are derived.

  4. 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.

  5. Closed-loop analysis and control of a non-inverting buck-boost converter

    NASA Astrophysics Data System (ADS)

    Chen, Zengshi; Hu, Jiangang; Gao, Wenzhong

    2010-11-01

    In this article, a cascade controller is designed and analysed for a non-inverting buck-boost converter. The fast inner current loop uses sliding mode control. The slow outer voltage loop uses the proportional-integral (PI) control. Stability analysis and selection of PI gains are based on the nonlinear closed-loop error dynamics incorporating both the inner and outer loop controllers. The closed-loop system is proven to have a nonminimum phase structure. The voltage transient due to step changes of input voltage or resistance is predictable. The operating range of the reference voltage is discussed. The controller is validated by a simulation circuit. The simulation results show that the reference output voltage is well-tracked under system uncertainties or disturbances, confirming the validity of the proposed controller.

  6. 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.

  7. Converter Circuit «Voltage-Voltage» Investigation for Power Calibrator

    NASA Astrophysics Data System (ADS)

    Fomichev, Yu M.; Silushkin, S. V.; Mylnikova, T. S.

    2016-01-01

    The paper presents possible circuits to construct a voltage-voltage converter for the calibrator of fictitious power. The problems of circuit solutions were experimentally identified, and the ways of their elimination were found. One of the main problems of convectors is to provide small harmonic distortions and additional phase shift. The use of deep negative instantaneous value feedback helps to provide the desired level of nonlinear distortions and to reduce the phase shift. Corrective circuits are used to ensure the stability of the transducer at greater depths of the feedback; the half-period average value or rms value feedback is used to ensure the stability and accuracy of conversion. However, the accuracy of the power calibrator can be upgraded and its work for various types of loads can be ensured by means of application follower circuit with modern electronic components which are also discussed in the paper.

  8. Novel distributed feedback lightwave circuit elements

    NASA Astrophysics Data System (ADS)

    Daǧ, Ceren B.; Anil, Mehmet A.; Serpengüzel, Ali

    2015-02-01

    The devices that are variations of inter-and intracoupled meandering optical waveguides are proposed as the lightwave circuit elements that exhibit distributed feedback. A preliminary transfer matrix method analysis is applied in frequency domain, taking the coupling purely directional and with constant coefficient on geometrically symmetric and anti-symmetric devices. The meandering loop mirror is the building block of all meandering waveguide based lightwave circuit elements. The simplest uncoupled meandering distributed feedback structure exhibits Rabi splitting in the transmittance spectrum. The symmetric and antisymmetric coupled meandering distributed feedback geometries can be utilized as band-pass, Fano, or Lorentzian filters or Rabi splitters. Meandering waveguide distributed feedback structures with a variety of spectral responses can be designed for a variety of lightwave circuit element functions and can be implemented with generality due to the analytic approach taken.

  9. Particle deformation induced by AFM tapping under different setpoint voltages

    NASA Astrophysics Data System (ADS)

    Wu, Chung-Lin; Farkas, Natalia; Dagata, John A.; He, Bo-Ching; Fu, Wei-En

    2014-09-01

    The measured height of polystyrene nanoparticles varies with setpoint voltage during atomic force microscopy (AFM) tapping-mode imaging. Nanoparticle height was strongly influenced by the magnitude of the deformation caused by the AFM tapping forces, which was determined by the setpoint voltage. This influence quantity was studied by controlling the operational AFM setpoint voltage. A test sample consisting of well-dispersed 60-nm polystyrene and gold nanoparticles co-adsorbed on poly-l-lysine-coated mica was studied in this research. Gold nanoparticles have not only better mechanical property than polystyrene nanoparticles, but also obvious facets in AFM phase image. By using this sample of mixed nanoparticles, it allows us to confirm that the deformation resulted from the effect of setpoint voltage, not noise. In tapping mode, the deformation of polystyrene nanoparticles increased with decreasing setpoint voltage. Similar behavior was observed with both open loop and closed loop AFM instruments.

  10. HIGH VOLTAGE GENERATOR

    DOEpatents

    Zito, G.V.

    1959-04-21

    This patent relates to high voltage supply circuits adapted for providing operating voltages for GeigerMueller counter tubes, and is especially directed to an arrangement for maintaining uniform voltage under changing conditions of operation. In the usual power supply arrangement for counter tubes the counter voltage is taken from across the power supply output capacitor. If the count rate exceeds the current delivering capaciiy of the capacitor, the capacitor voltage will drop, decreasing the counter voltage. The present invention provides a multivibrator which has its output voltage controlled by a signal proportional to the counting rate. As the counting rate increases beyond the current delivering capacity of the capacitor, the rectified voltage output from the multivibrator is increased to maintain uniform counter voltage.

  11. 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.

  12. Closed orbit feedback with digital signal processing

    SciTech Connect

    Chung, Y.; Kirchman, J.; Lenkszus, F.

    1994-08-01

    The closed orbit feedback experiment conducted on the SPEAR using the singular value decomposition (SVD) technique and digital signal processing (DSP) is presented. The beam response matrix, defined as beam motion at beam position monitor (BPM) locations per unit kick by corrector magnets, was measured and then analyzed using SVD. Ten BPMs, sixteen correctors, and the eight largest SVD eigenvalues were used for closed orbit correction. The maximum sampling frequency for the closed loop feedback was measured at 37 Hz. Using the proportional and integral (PI) control algorithm with the gains Kp = 3 and K{sub I} = 0.05 and the open-loop bandwidth corresponding to 1% of the sampling frequency, a correction bandwidth ({minus}3 dB) of approximately 0.8 Hz was achieved. Time domain measurements showed that the response time of the closed loop feedback system for 1/e decay was approximately 0.25 second. This result implies {approximately} 100 Hz correction bandwidth for the planned beam position feedback system for the Advanced Photon Source storage ring with the projected 4-kHz sampling frequency.

  13. Voltage tunable polymer laser device

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  14. 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.

  15. 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.

  16. 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…

  17. Monolithic amplifier with stable, high resistance feedback element and method for fabricating the same

    DOEpatents

    O`Connor, P.

    1998-08-11

    A monolithic amplifier includes a stable, high resistance feedback circuit and a dynamic bias circuit. The dynamic bias circuit is formed with active elements matched to those in the amplifier and feedback circuit to compensate for variations in the operating and threshold voltages thereby maintaining a stable resistance in the feedback circuit. 11 figs.

  18. Monolithic amplifier with stable, high resistance feedback element and method for fabricating the same

    DOEpatents

    O'Connor, Paul

    1998-08-11

    A monolithic amplifier includes a stable, high resistance feedback circuit and a dynamic bias circuit. The dynamic bias circuit is formed with active elements matched to those in the amplifier and feedback circuit to compensate for variations in the operating and threshold voltages thereby maintaining a stable resistance in the feedback circuit.

  19. Heating power feedback control for CO2 laser fusion splicers

    NASA Astrophysics Data System (ADS)

    Zheng, Wenxin; Sugawara, Hiroshi; Mizushima, Toshirou; Klimowych, William

    2013-02-01

    A novel feedback control method has been developed for an automated splicer using a CO2 laser as the heating element. The feedback method employs a sensor for laser beam power and CMOS cameras as sensors for fiber luminescence which is directly related to glass temperature. The CO2 laser splicer with this type of feedback system provides a consistent platform for the fiber laser and bio-medical industry for fabrication of fused glass components such as tapers, couplers, combiners, mode-field adaptors, and fusion splices. With such a closed loop feedback system, both splice loss and peak-to-peak taper ripple are greatly reduced.

  20. Automated setup for magnetic hysteresis characterization based on a voltage controlled current source with 500 kHz full power bandwidth and 10 A peak-to-peak current

    SciTech Connect

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

    2015-04-15

    This paper describes the design of a system for the characterization of magnetic hysteresis behavior in soft ferrite magnetic cores. The proposed setup can test magnetic materials exciting them with controlled arbitrary magnetic field waveforms, including the capability of providing a DC bias, in a frequency bandwidth up to 500 kHz, with voltages up to 32 V peak-to-peak, and currents up to 10 A peak-to-peak. In order to have an accurate control of the magnetic field waveform, the system is based on a voltage controlled current source. The electronic design is described focusing on closed loop feedback stabilization and passive components choice. The system has real-time hysteretic loop acquisition and visualization. The comparisons between measured hysteresis loops of sample magnetic materials and datasheet available ones are shown. Results showing frequency and thermal behavior of the hysteresis of a test sample prove the system capabilities. Moreover, the B-H loops obtained with a multiple waveforms excitation signal, including DC bias, are reported. The proposal is a low-cost and replicable solution for hysteresis characterization of magnetic materials used in power electronics.

  1. Inverse spin Hall effect in a closed loop circuit

    SciTech Connect

    Omori, Y.; Auvray, F.; Wakamura, T.; Niimi, Y.; Fert, A.

    2014-06-16

    We present measurements of inverse spin Hall effects (ISHEs), in which the conversion of a spin current into a charge current via the ISHE is detected not as a voltage in a standard open circuit but directly as the charge current generated in a closed loop. The method is applied to the ISHEs of Bi-doped Cu and Pt. The derived expression of ISHE for the loop structure can relate the charge current flowing into the loop to the spin Hall angle of the SHE material and the resistance of the loop.

  2. Automatic voltage imbalance detector

    DOEpatents

    Bobbett, Ronald E.; McCormick, J. Byron; Kerwin, William J.

    1984-01-01

    A device for indicating and preventing damage to voltage cells such as galvanic cells and fuel cells connected in series by detecting sequential voltages and comparing these voltages to adjacent voltage cells. The device is implemented by using operational amplifiers and switching circuitry is provided by transistors. The device can be utilized in battery powered electric vehicles to prevent galvanic cell damage and also in series connected fuel cells to prevent fuel cell damage.

  3. Mixed voltage VLSI design

    NASA Technical Reports Server (NTRS)

    Panwar, Ramesh; Rennels, David; Alkalaj, Leon

    1993-01-01

    A technique for minimizing the power dissipated in a Very Large Scale Integration (VLSI) chip by lowering the operating voltage without any significant penalty in the chip throughput even though low voltage operation results in slower circuits. Since the overall throughput of a VLSI chip depends on the speed of the critical path(s) in the chip, it may be possible to sustain the throughput rates attained at higher voltages by operating the circuits in the critical path(s) with a high voltage while operating the other circuits with a lower voltage to minimize the power dissipation. The interface between the gates which operate at different voltages is crucial for low power dissipation since the interface may possibly have high static current dissipation thus negating the gains of the low voltage operation. The design of a voltage level translator which does the interface between the low voltage and high voltage circuits without any significant static dissipation is presented. Then, the results of the mixed voltage design using a greedy algorithm on three chips for various operating voltages are presented.

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

    PubMed

    Nguyen, L K; Kulasiri, D

    2011-03-01

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

  5. 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.

  6. 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.

  7. 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

  8. High Voltage SPT Performance

    NASA Technical Reports Server (NTRS)

    Manzella, David; Jacobson, David; Jankovsky, Robert

    2001-01-01

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

  9. Blind loop syndrome

    MedlinePlus

    Blind loop syndrome occurs when digested food slows or stops moving through part of the intestines. This ... The name of this condition refers to the "blind loop" formed by part of the intestine that ...

  10. RF Voltage Measurements on ICRF Antennas

    NASA Astrophysics Data System (ADS)

    Bell, G. L.; Goulding, R. H.; Hoffman, D. J.; Wilgen, J. B.; Zhang, H. M.; Ryan, P. M.; Syed, G. M. S.; Kaye, A. S.

    1996-11-01

    Particle and heat flux on the plasma facing surfaces of high-power RF antennas used in fusion devices can result in damage to the antenna structures. High impedance capacitive probe measurements of the RF voltages on Faraday shields of several loop antennas indicate that voltages as high as 30% of the drive voltage can exist for 0/0 phasing (D.J. Hoffman, et al., AIP Conf. Proc. 355), 368 (Palm Spgs., CA, 1995).. These voltages can contribute to increased energy deposition on the antenna owing to increased RF sheath voltages. We report on continued efforts to understand the source and to control these RF voltages. E and B field distributions have been measured on the mock-up of the JET A2 antenna using standard B-dot probes and novel E-field probes positioned with a new automated scanning system. These data are compared with calculated fields from 3-D antenna models. The measurements demonstrate the dependency of the surface E-fields on the phasing of the strap currents and show the charge accumulation at the antenna top and bottom predicted by the models.

  11. Measurement of rf voltages on the plasma-touching surfaces of ICRF antennas

    SciTech Connect

    Hoffman, D.J.; Baity, F.W.; Bell, G.L.; Bigelow, T.S.; Caughman, J.B.O.; Goulding, R.H.; Haste, G.R.; Ryan, P.M.; Zhang, H.

    1995-09-01

    Measurements of the rf voltages on Faraday shields and protection bumpers have been made for several loop antennas, including the mock-up antenna and Al for JET, the original antenna for Tore Supra, the present ASDEX-U antenna, and the folded waveguide. The loop antennas show voltages that scale to {approx}12 kV for a maximum input voltage of 30 kV with 0/0 phasing. The voltages are dramatically reduced for 0/{pi} phasing. These voltages are significant in that they can substantially increase the rf sheath potential beyond the levels associated with the simple electromagnetic field linkage from the current straps that results in plasma heating. In this paper, we investigate and measure the source of these voltages, their scaling with antenna impedance, and the differences between the loop arrays.

  12. Measurement of rf voltages on the plasma-touching surfaces of ICRF antennas

    SciTech Connect

    Hoffman, D.J.; Baity, F.W.; Bell, G.L.; Bigelow, T.S.; Caughman, J.B.; Goulding, R.H.; Haste, G.R.; Ryan, P.M.; Zhang, H.

    1996-02-01

    Measurements of the rf voltages on Faraday shields and protection bumpers have been made for several loop antennas, including the mock-up antenna and A1 for JET, the original antenna for Tore Supra, the present ASDEX-U antenna, and the folded waveguide. The loop antennas show voltages that scale to {approx_equal}12 kV for a maximum input voltage of 30 kV with 0/0 phasing. The voltages are dramatically reduced for 0/{pi} phasing. These voltages are significant in that they can substantially increase the rf sheath potential beyond the levels associated with the simple electromagnetic field linkage from the current straps that results in plasma heating. In this paper, we investigate and measure the source of these voltages, their scaling with antenna impedance, and the differences between the loop arrays. {copyright} {ital 1996 American Institute of Physics.}

  13. Measurement of rf voltages on the plasma-touching surfaces of ICRF antennas

    NASA Astrophysics Data System (ADS)

    Hoffman, D. J.; Baity, F. W.; Bell, G. L.; Bigelow, T. S.; Caughman, J. B. O.; Goulding, R. H.; Haste, G. R.; Ryan, P. M.; Zhang, H.

    1996-02-01

    Measurements of the rf voltages on Faraday shields and protection bumpers have been made for several loop antennas, including the mock-up antenna and A1 for JET, the original antenna for Tore Supra, the present ASDEX-U antenna, and the folded waveguide. The loop antennas show voltages that scale to ≊12 kV for a maximum input voltage of 30 kV with 0/0 phasing. The voltages are dramatically reduced for 0/π phasing. These voltages are significant in that they can substantially increase the rf sheath potential beyond the levels associated with the simple electromagnetic field linkage from the current straps that results in plasma heating. In this paper, we investigate and measure the source of these voltages, their scaling with antenna impedance, and the differences between the loop arrays.

  14. 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

  15. Development of a design tool for closed-loop digital vibrometer.

    PubMed

    Melchionni, Dario; Magnani, Alessandro; Pesatori, Alessandro; Norgia, Michele

    2015-11-10

    The closed-loop technique has been demonstrated as a possible configuration to design a vibrometer based upon self-mixing interferometry. The electronic feedback loop allows a better linearity while extending the linearity range of a self-mixing interferometer. A deep analysis of the feedback loop is carried out in order to improve stability and performance through a digital approach. This work describes first the simulation of the closed-loop vibrometer, and then the performance obtained through its implementation on an FPGA based prototype. PMID:26560797

  16. Feedback on Feedback--Does It Work?

    ERIC Educational Resources Information Center

    Speicher, Oranna; Stollhans, Sascha

    2015-01-01

    It is well documented that providing assessment feedback through the medium of screencasts is favourably received by students and encourages deeper engagement with the feedback given by the language teacher (inter alia Abdous & Yoshimura, 2010; Brick & Holmes, 2008; Cann, 2007; Stannard, 2007). In this short paper we will report the…

  17. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    PubMed Central

    2010-01-01

    Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo). Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel). It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its refractory characteristics

  18. Internal and external feedback circuits for skilled forelimb movement

    PubMed Central

    Azim, Eiman; Fink, Andrew J.P.; Jessell, Thomas M.

    2015-01-01

    Skilled motor behavior emerges from interactions between efferent neural pathways that induce muscle contraction and feedback systems that report and refine movement. Two broad classes of feedback projections modify motor output, one from the periphery and a second that originates within the central nervous system. The mechanisms through which these pathways influence movement remain poorly understood, however. Here we discuss recent studies that delineate spinal circuitry that binds external and internal feedback pathways to forelimb motor behavior. A spinal presynaptic inhibitory circuit regulates the strength of external feedback, promoting limb stability during goal-directed reaching. A distinct excitatory propriospinal circuit conveys copies of motor commands to the cerebellum, establishing an internal feedback loop that rapidly modulates forelimb motor output. The behavioral consequences of manipulating these two circuits reveal distinct controls on motor performance, and provide an initial insight into feedback strategies that underlie skilled forelimb movement. PMID:25699987

  19. Effects of unwanted feedback on synchronized chaotic optical communications

    NASA Astrophysics Data System (ADS)

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

    2006-04-01

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

  20. Closed-Loop Control of Epilepsy by Transcranial Electrical Stimulation

    PubMed Central

    Berényi, Antal; Belluscio, Mariano; Mao, Dun; Buzsáki, György

    2016-01-01

    Many neurological and psychiatric diseases are associated with clinically detectable, altered brain dynamics. The aberrant brain activity, in principle, can be restored through electrical stimulation. In epilepsies, abnormal patterns emerge intermittently, and therefore, a closed-loop feedback brain control that leaves other aspects of brain functions unaffected is desirable. Here, we demonstrate that seizure-triggered, feedback transcranial electrical stimulation (TES) can dramatically reduce spike-and-wave episodes in a rodent model of generalized epilepsy. Closed-loop TES can be an effective clinical tool to reduce pathological brain patterns in drug-resistant patients. PMID:22879515